Search

Simple Summary: Completion lobectomy (CL) entails the resection of the remaining pulmonary lobe subsequent to wedge resection or segmentectomy. Indications for CL include reoperations for multiple or relapsed lung cancers and metastatic lung tumors, and the prognostic advantage of these procedures has been widely reported. However, ipsilateral surgical treatments, particularly within the same lobe, present challenges due to the development of intrapleural adhesions, rendering reoperation more difficult and time-consuming. VATS has emerged as the gold standard in the surgical treatment of early-stage NSCLC, offering superior postoperative outcomes when compared to thoracotomy. Its efficacy has been well established, even during complex procedures. However, its application in ipsilateral reoperations remains anecdotal, and to the best of our knowledge, no studies have analyzed the safety and efficacy of uniportal-VATS in this setting. This paper aims to evaluate the role of iniportal-VATS in CL long after wedge resection or anatomical segmentectomy in the same lobe. Background: Completion lobectomy (CL) following a prior resection in the same lobe may be complicated by severe pleural or hilar adhesions. The role of uniportal video-assisted thoracoscopic surgery (U-VATS) has never been evaluated in this setting. Methods: Data were collected from two Italian centers. Between 2015 and 2022, 122 patients (60 men and 62 women, median age 67.7 ± 8.913) underwent U-VATS CL at least 4 weeks after previous lung surgery. Results: Twenty-eight (22.9%) patients were affected by chronic obstructive pulmonary disease (COPD) and twenty-five (20.4%) were active smokers. Among the cohort, the initial surgery was performed using U-VATS in 103 (84.4%) patients, triportal-VATS in 8 (6.6%), and thoracotomy in 11 (9.0%). Anatomical segmentectomy was the initial surgery in 46 (37.7%) patients, while hilar lymphadenectomy was performed in 16 (13.1%) cases. CL was performed on 110 (90.2%) patients, segmentectomy on 10 (8.2%), and completion pneumonectomy on 2 (1.6%). Upon reoperation, moderate pleural adhesions were observed in 38 (31.1%) patients, with 2 (1.6%) exhibiting strong adhesions. Moderate hilar adhesions were found in 18 (14.8%) patients and strong adhesions in 11 (9.0%). The median operative time was 203.93 ± 74.4 min. In four (3.3%) patients, PA taping was performed. One patient experienced intraoperative bleeding that did not require conversion to thoracotomy. Conversion to thoracotomy was necessary in three (2.5%) patients. The median postoperative drainage stay and postoperative hospital stay were 5.67 ± 4.44 and 5.52 ± 2.66 days, respectively. Postoperative complications occurred in 34 (27.9%) patients. Thirty-day mortality was null. Histology was the only factor found to negatively influence intraoperative outcomes (p = 0.000). Factors identified as negatively impacting postoperative outcomes at univariate analyses were male sex (p = 0.003), age > 60 years (p = 0.003), COPD (p = 0.014), previous thoracotomy (p = 0.000), previous S2 segmentectomy (p = 0.001), previous S8 segmentectomy (p = 0.008), and interval between operations > 5 weeks (p= 0.005). In multivariate analysis, only COPD confirmed its role as an independent risk factor for postoperative complications (HR: 5.12, 95% CI (1.07–24.50), p = 0.04). Conclusions: U-VATS CL seems feasible and safe after wedge resection and anatomical segmentectomy. [ABSTRACT FROM AUTHOR]

Simple Summary: Percutaneous cryoablation (PCA) is a minimally invasive procedure that should be considered in comorbid patients with stage T1 renal tumours who are suboptimal candidates for partial nephrectomy (PN). However, there is a scarcity of scientific data regarding the efficacy of PCA. The aim of this meta-analysis was to compare PCA and PN in terms of complications, renal function and survival outcomes. According to this analysis, PCA is associated with fewer complications than PN. Moreover, in tumours up to 4 cm, it provides the same time without local recurrence. Therefore, PCA should be proposed to patients with cT1 renal tumours who are not fit for PN but want to undergo a radical treatment. Percutaneous cryoablation (PCA) can be an alternative to partial nephrectomy (PN) in selected patients with stage T1 renal tumours. Existing meta-analyses regarding ablative techniques compared both laparoscopic and PCA with PN. That is why we decided to perform a meta-analysis that focused solely on PCA. The aim of this study was to compare the complications and functional and oncological outcomes between PCA and PN. A systematic literature search was performed in January 2024. Data for dichotomous and continuous variables were expressed as pooled odds ratios (ORs) and mean differences (MDs), both with 95% confidence intervals (CIs). Effect measures for the local recurrence-free survival (LRFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS) were expressed as pooled hazard ratios with 95% CIs. Among 6487 patients included in the 14 selected papers, 1554 (23.9%) and 4924 (76.1%) underwent PCA and PN, respectively. Compared with the PN group, patients undergoing PCA had significantly lower overall and major postoperative complication rates. There was no difference in renal function between PCA and PN groups. When analysing collective data for cT1 renal carcinoma, PCA was associated with worse LRFS compared with PN. However, subgroup analysis revealed that in the case of PCA, LRFS was not decreased in patients with cT1a tumours. Moreover, patients undergoing robotic-assisted PN had improved LRFS compared with those undergoing PCA. No significant differences were observed between PCA and PN in terms of MFS and CSS. Finally, PCA was associated with worse OS than PN in both collective and subgroup analyses. In conclusion, PCA is associated with favourable postoperative complication rates relative to PN. Regarding LRFS, PCA is not worse than PN in cT1a tumours but has a substantially relevant disadvantage in cT1b tumours. Also, RAPN might be the only surgical modality that provides better LRFS than PCA. In cT1 tumours, PCA shows MFS and CSS comparable to PN. Lastly, PCA is associated with a shorter OS than PN. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor gene (EGFR) Exon 20 insertion mutations (Exon20ins) used to have poor outcomes after the failure of platinum-based therapies. Amivantamab, a drug that targets two proteins involved in NSCLC (EGFR/MET), was developed and studied in the CHRYSALIS clinical trial. This paper summarizes an analysis comparing outcomes for amivantamab from CHRYSALIS to the outcomes for a mix of treatments that were used in real-world clinical practice (real-world physician's choice [RWPC]). RWPC data were collected from hospitals across Europe in the CATERPILLAR real-world evidence (RWE) study. The outcomes of 114 patients from CHRYSALIS were compared to 55 lines of treatment (LOTs) from CATERPILLAR-RWE, accounting for differences in patient characteristics between the two populations. Overall, the results show that amivantamab was at least twice as good as RWPC for platinum pre-treated patients in terms of tumor response and survival rates. Patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor gene (EGFR) Exon 20 insertions (Exon20ins) at the second line and beyond (2L+) have an unmet need for new treatment. Amivantamab, a bispecific EGFR- and MET-targeted antibody, demonstrated efficacy in this setting in the phase 1b, open-label CHRYSALIS trial (NCT02609776). The primary objective was to compare the efficacy of amivantamab to the choices made by real-world physicians (RWPC) using an external control cohort from the real-world evidence (RWE) chart review study, CATERPILLAR-RWE. Adjustment was conducted to address differences in prognostic variables between cohorts using inverse probability weighting (IPW) and covariate adjustments based on multivariable regression. In total, 114 patients from CHRYSALIS were compared for 55 lines of therapy from CATERPILLAR-RWE. Baseline characteristics were comparable between the amivantamab and IPW-weighted RWPC cohorts. For amivantamab versus RWPC using IPW adjustment, the response rate ratio for the overall response was 2.14 (p = 0.0181), and the progression-free survival (PFS), time-to-next-treatment (TTNT) and overall survival (OS) hazard ratios (HRs) were 0.42 (p < 0.0001), 0.47 (p = 0.0063) and 0.48 (p = 0.0207), respectively. These analyses provide evidence of clinical and statistical benefits across multiple outcomes and adjustment methods, of amivantamab in platinum pre-treated patients with advanced NSCLC harboring EGFR Exon20ins. These results confirm earlier comparisons versus pooled national registry data. [ABSTRACT FROM AUTHOR]

Simple Summary: Brain MRI scans often require different imaging sequences based on tissue types, posing a common challenge. In our research, we propose a method that utilizes Generative Adversarial Networks (GAN) to translate T2-weighted-Fluid-attenuated-Inversion-Recovery (FLAIR) MRI volumes into T2-Weighted (T2W) volumes, and vice versa. To evaluate the effectiveness of our approach, we introduce a novel evaluation schema that incorporates radiomic features. We train two distinct GAN-based architectures, namely Cycle GAN and Dual Cycle-Consistent Adversarial network (DC2Anet), using 510 pair-slices from 102 patients. Our findings indicate that the generative methods can produce results similar to the original sequence without significant changes in radiometric features. This method has the potential to assist clinicians in making informed decisions based on generated images when alternative sequences are unavailable, or time constraints prevent re-scanning MRI patients. One of the most common challenges in brain MRI scans is to perform different MRI sequences depending on the type and properties of tissues. In this paper, we propose a generative method to translate T2-Weighted (T2W) Magnetic Resonance Imaging (MRI) volume from T2-weight-Fluid-attenuated-Inversion-Recovery (FLAIR) and vice versa using Generative Adversarial Networks (GAN). To evaluate the proposed method, we propose a novel evaluation schema for generative and synthetic approaches based on radiomic features. For the evaluation purpose, we consider 510 pair-slices from 102 patients to train two different GAN-based architectures Cycle GAN and Dual Cycle-Consistent Adversarial network (DC2Anet). The results indicate that generative methods can produce similar results to the original sequence without significant change in the radiometric feature. Therefore, such a method can assist clinics to make decisions based on the generated image when different sequences are not available or there is not enough time to re-perform the MRI scans. [ABSTRACT FROM AUTHOR]

Simple Summary: Peritoneal metastases have a poor prognosis, and one potential treatment option is cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). The specific role of HIPEC is still poorly defined. In this cross-sectional study, we systematically analyzed all HIPEC trials registered on ClinicalTrials.gov to identify current research areas and to provide a perspective on expected outcomes. Only 11% (n = 26) of HIPEC trials registered on ClinicalTrials.gov (n = 234) have been published. The registered trials are very heterogeneous regarding methodological approaches and study designs. Currently, research is being conducted on 20 different drugs. The most studied cancers in HIPEC trials are peritoneal metastatic colorectal tumors, gastric cancer, and ovarian cancer. Introduction: Over the past two decades, cytoreductive surgery and HIPEC has improved outcomes for selected patients with peritoneal metastasis from various origins. This is a cross-sectional study with descriptive analyses of HIPEC trials registered on ClinicalTrials.gov. This study aimed to characterize clinical trials on HIPEC registered on ClinicalTrials.gov with the primary objective of identifying a trial focus and to examine whether trial results were published. Methods: The search included trials registered from 1 January 2001 to 14 March 2022. We examined the associations of exposure variables and other trial features with two primary outcomes: therapeutic focus and results reporting. Results: In total, 234 clinical trials were identified; 26 (11%) were already published, and 15 (6%) trials have reported their results but have not been published as full papers. Among ongoing nonpublished trials, 81 (39%) were randomized, 30 (14%) were blinded, n = 39 (20%) were later phase trials (i.e., phases 3 and 4), n = 152 (73%) were from a single institution, and 91 (44%) had parallel groups. Most of the trials were recruiting at the time of this analysis (75, 36%), and 39 (20%) were completed but had yet to publish results. In total, 68% of the trials focused on treatment strategies, and 53% investigated the oncological outcome. The most studied neoplasms for HIPEC trials were peritoneally metastasized colorectal cancer (32%), gastric cancer (29%), and ovarian cancer (26%). Twenty different drugs were analyzed in these clinical trials. Conclusions: Many study results are awaited from ongoing HIPEC trials. Most HIPEC trials focused on gastric, colorectal, or ovarian cancer. Many clinical trials were identified involving multiple entities and chemotherapeutic agents. [ABSTRACT FROM AUTHOR]

Simple Summary: Uveal melanoma is a rare form of melanoma but is the most common tumor in the eye. Despite having effective treatments for the initial tumor, many patients experience the spread of their cancer to distant body sites. There is no uniform way of treating metastatic disease, but physicians often use therapies that harness the patient's immune system because these same treatments have been very effective in other types of melanoma. Not all patients respond to this therapy though, and some develop toxicity related to the treatment. The goal of this paper was to identify features or blood markers that may help determine response to treatment early. Specifically, we analyzed a molecule called lactate dehydrogenase (LDH) and the ratio of different white blood cells at the start of therapy and 2 months after treatment was started. We found that these non-invasive blood markers could be useful in determining which patients are responding to treatment. Background: There is no standardized treatment for metastatic uveal melanoma (MUM) but immune checkpoint inhibitors (ICI) are increasingly used. While ICI has transformed the survival of metastatic cutaneous melanoma, MUM patients do not equally benefit. Factors known to affect ICI response include the hematologic markers, lactate dehydrogenase (LDH) and neutrophil:lymphocyte ratio (NLR). We evaluated the prognostic value of LDH and NLR at the start of ICI and on treatment in MUM. Methods: MUM patients were treated between August 2006 and May 2022 with combination ipilimumab/nivolumab or ipilimumab/nivolumab/pembrolizumab single-agent therapy. Univariable (UVA) and multivariable (MVA) analyses were used to assess the prognostic value of predefined baseline factors on progression-free (PFS) and overall survival (OS). Results: In forty-six patients with MUM treated with ICI, elevated baseline and on-treatment LDH was prognostic for OS (start of ICI, HR (95% CI): 3.6 (1.9–7.0), p < 0.01; on-treatment, HR (95% CI): 3.7 (1.6–8.8), p < 0.01) and PFS (start of ICI, (HR (95% CI): 2.8 (1.5–5.4), p < 0.0001); on-treatment LDH (HR (95% CI): 2.2 (1.1–4.3), p < 0.01). On-treatment NLR was prognostic for PFS (HR (95% CI): 1.9 (1.0–3.9), p < 0.01). On-treatment LDH remained an important contributor to survival on MVA (OS: HR (95% CI): 1.001 (1.00–1.002), p < 0.05); PFS: HR (95% CI): 1.001 (1.00–1.002), p < 0.01). Conclusions: This study demonstrates that LDH and NLR could be useful in the prognostication of MUM patients treated with ICI. Additional studies are needed to confirm the importance of these and other prognostic biomarkers. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunotherapy has revolutionized the therapeutic options for patients living with non-small-cell lung cancer (NSCLC). Despite the unprecedented results achieved through immunotherapy, a low body mass index, which is referred to as cachexia, and the bacterial composition of the gut microbiota are known factors associated with resistance. In this paper, we enrolled 113 Japanese patients with NSCLC and demonstrated that cachexia was associated with poor outcomes. Moreover, microbiota sequencing revealed that patients without cachexia had abundant bacteria that correlated with a beneficial outcome. Altogether, our results demonstrated an association between the gut microbiota and cachexia. This study provides a rationale to launch clinical trials on the outcome of shifting the microbiota composition of patients with cachexia that are receiving immunotherapy. Cancer cachexia exerts a negative clinical influence on patients with advanced non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI). The prognostic impact of body weight change during ICI treatment remains unknown. The gut microbiota (GM) is a key contributor to the response to ICI therapy in cancer patients. However, the association between cancer cachexia and GM and their association with the response to ICIs remains unexplored. This study examined the association of cancer cachexia with GM composition and assessed the impact of GM on clinical outcomes in patients with NSCLC treated with ICIs. In this observational, prospective study, which included 113 Japanese patients with advanced NSCLC treated with ICIs, the prevalence of cachexia was 50.4% (57/113). The median progression-free survival (PFS) and overall survival (OS) were significantly shorter in the cachexia group than in the non-cachexia group (4.3 vs. 11.6 months (p = 0.003) and 12.0 months vs. not reached (p = 0.02), respectively). A multivariable analysis revealed that baseline cachexia was independently associated with a shorter PFS. Moreover, a gain in body weight from the baseline (reversible cachexia) was associated with a significantly longer PFS and OS compared to irreversible cachexia. Microbiome profiling with 16S rRNA analysis revealed that the cachexia group presented an overrepresentation of the commensal bacteria, Escherichia-Shigella and Hungatella, while the non-cachexia group had a preponderance of Anaerostipes, Blautia, and Eubacterium ventriosum. Anaerostipes and E. ventriosum were associated with longer PFS and OS. Moreover, a cachexia status correlated with the systemic inflammatory marker-derived-neutrophil-to-lymphocytes ratio (dNLR) and Lung Immune Prognostic Index (LIPI) indexes. Our study demonstrates that cachexia and longitudinal bodyweight change have a prognostic impact on patients with advanced NSCLC treated with ICI therapy. Moreover, our study demonstrates that bacteria associated with ICI resistance are also linked to cachexia. Targeted microbiota interventions may represent a new type of treatment to overcome cachexia in patients with NSCLC. [ABSTRACT FROM AUTHOR]

Simple Summary: When it comes to advanced vulval cancer management, there is a critical quandary to consider. This is owing to the severe negative impact of demolitive surgery on women who are afflicted by both functional and psychological consequences of the procedure. Primary closure of vulvar and/or perineal defects can be accomplished without difficulty in many situations, but this is accompanied by tension of the skin closure and distortion of the anatomy. In these circumstances, reconstructive surgery will be required to restore the anatomical and functional characteristics of the vulva. In this paper, we share our substantial expertise of primary closure versus reconstruction after demolitive surgery of advanced vulvar cancer, and we discuss our findings in light of the literature. (1) Background: plastic reconstruction in vulvar surgery can lead to a better treatment outcome than primary closure. This study aims to compare the preoperative parameters (co-morbidities and tumor size) and postoperative results (tumor free margins and wound healing) between the primary closure and reconstructive surgery after vulvar cancer surgery; (2) Methods: this is a retrospective analysis of prospectively collected data from 2009 to 2021 at a tertiary cancer institution; (3) Results: 177 patients were included in the final analysis (51 patients had primary closure PC and 126 had reconstructive surgery RS). About half (49%) of the PC patients had no co-morbidities (p = 0.043). The RS group had a 45 mm median maximal tumor diameter compared to the PC group's 23 mm (p = 0.013). More than 90% of RS and 80% of PC had tumor-free margins (p = 0.1). Both groups had anterior vulvar excision as the most common surgery (52.4% RS vs. 23.5% PC; p = 0.001). Both groups had identical rates of wound healing disorders. In a median follow-up of 39 months; recurrent disease was found in 23.5% of PC vs. 10.3% in RS (p = 0.012). In terms of overall survival there was no significant difference between the both groups; (4) Conclusions: reconstructive vulvar surgery enables enhanced complete resection rates of larger vulvar tumors with better anatomical restoration and a comparable wound recovery in comparison to primary closure. This results in a lower recurrence rate despite the increased tumor volume. [ABSTRACT FROM AUTHOR]

Simple Summary: Sorafenib has been the standard of care for advanced hepatocellular carcinoma (aHCC) patients since 2008. Recently, new therapies have been funded that provide increased survival in this patient population. The aim of our retrospective cohort study of linked administrative databases in Ontario was to understand the characteristics of patients with aHCC, their treatment patterns, survival outcomes, healthcare resource utilization (HCRU), and costs. We observed that patients who received systemic therapy for aHCC had a higher median overall survival (mOS) from diagnosis compared to patients who received other systemic therapies or a locoregional treatment (LRT). The mean cost per patient was $52,166 CAD for all the patients in the study, with inpatient hospitalizations and oral medications as the largest cost drivers. The therapeutic landscape for aHCC has evolved in recent years, necessitating a comprehensive analysis of treatment patterns, clinical outcomes, HCRU, and costs to contextualize emerging treatments. This study aimed to investigate these outcomes using real-world data from Ontario, Canada. This retrospective cohort study was conducted using linked administrative databases from April 2010 to March 2020. Patients diagnosed with aHCC were included, and their clinical and demographic characteristics were analyzed, as well as treatment patterns, survival, HCRU, and economic burden. Among 7322 identified patients, 802 aHCC patients met the eligibility criteria for inclusion in the study. Treatment subgroups included 1L systemic therapy (53.2%), other systemic treatments (4.5%), LRT (9.0%), and no treatment (33.3%). The median age was 66 years, and the majority were male (82%). The mOS for the entire cohort from diagnosis was 6.5 months. However, patients who received 1L systemic therapy had an mOS of 9.0 months, which was significantly higher than the other three subgroups. The mean cost per aHCC-treated patient was $49,640 CAD, with oral medications and inpatient hospitalizations as the largest cost drivers. The results underscore the need for the continuous evaluation and optimization of HCC management strategies in the era of evolving therapeutic options. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to explore the relationship of the pN stage of thyroid cancer (TC) and ultrasound hypoechogenicity with encapsulation and vascular invasion. A retrospective study involving 678 TC patients revealed that a greater pN stage was correlated with encapsulation and vascular invasion as well as with positive hypoechogenicity. These findings have significant prognostic and clinical implications for managing TC. Discovering these correlations confirms the importance of the TNM scale in stratifying TC patients based on disease severity. The results suggest that the hypoechoic patterns observed on thyroid ultrasound may serve as indicators of aggressive tumour behaviour and increased invasion risk. This analysis highlights diverse invasion patterns among TC patients, which may have significant clinical implications for diagnostic processes and treatment strategy selection. Further research is necessary to validate these findings and explore new biomarkers and imaging methods to refine TC staging systems and improve TC patient care. In this retrospective study, the relationship between the pN stage of TC and the ultrasound hypoechogenicity of tumour encapsulation and vascular invasion was investigated. The data of a total of 678 TC patients were analysed. The goal of this study was to assess the significance of the pTNM score and preoperative ultrasound features in predicting cancer prognosis and guiding therapeutic decisions in patients with TC. The main research methods included a retrospective analysis of patient data, mainly the pTNM score and presence of tumour encapsulation and vascular invasion obtained from histopathological results and preoperative ultrasound imaging. Patients with well-differentiated TCs (papillary and follicular) were extracted from TC patients to better unify the results because of similar clinical strategies for these TCs. Significant associations were observed between advanced pN stage and the presence of encapsulation and vessel invasion. The majority of pN1a patients exhibited encapsulation (77.71%; p < 0.0001) and vascular invasion (75.30%; p < 0.0001), as did the majority of pN1b patients (100%; p < 0.0001 and 100%; p < 0.0001, respectively). Less than half of the patients with hypoeghogenic patterns presented with encapsulation (43.30%; p < 0.0001) and vascular invasion (43.52%; p < 0.0001), while the vast majority of patients without hypoechogenicity did not present with encapsulation (90.97%; p < 0.0001) or vascular invasion (90.97%; p < 0.0001). Hypoechogenicity was found to be indicative of aggressive tumour behaviour. The results of this study underscore the importance of accurate N staging in TC and suggests the potential use of ultrasound features in predicting tumour behaviour. Further research is needed to confirm these findings and explore additional prognostic markers to streamline TC management strategies and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Corticosteroid use for the treatment of immune related adverse events (irAEs) after immune checkpoint inhibitor (ICI) use comes with concerns of side effects and the potential abrogation of antitumor immunity. Relatedly, the impact of steroid-sparing immunosuppressive agents (SSIAs) for treatment of irAEs on tumor outcomes is not well known, and current literature on this topic is limited by study design and issues around immortal time bias. This retrospective case-control study accounts for immortal time bias via strategic statistical methodology. Our results suggest that SSIAs used for irAE treatment may not negatively impact cancer outcomes in malignant melanoma and non-small cell lung cancer. For patients with melanoma, our results demonstrated better progression free survival for patients treated with infliximab compared to patients treated with corticosteroid monotherapy for irAEs. This study supports the safety for utilizing SSIAs for irAE treatment in patients receiving immune checkpoint inhibitors. Our study also encourages accounting for immortal time bias in the design of other observational studies in this space to accurately convey results and draw clinically meaningful conclusions. Background: The effects of steroid-sparing immunosuppressive agents (SSIAs), used for the treatment of immune-related adverse events (irAEs), on immune checkpoint inhibitor (ICI) antitumor activity is not well known. We compared tumor outcomes of patients who received corticosteroid monotherapy (CS) versus a corticosteroid plus SSIA (CS-SSIA) for irAE treatment, using statistical methods to address immortal time bias. Methods: We conducted a retrospective case-control study on patients ≥ 18 years with melanoma or non-small-cell lung cancer (NSCLC) treated with ≥1 ICI at a quaternary care center between 1 January 2016 and 11 January 2021. Patients were divided into two cohorts: CS or CS-SSIA. We used propensity score nearest-neighbor matching to match on tumor type, stage, and prior lines of therapy. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Secondary outcomes included the time from the start of the irAE treatment to the irAE resolution. Hazard ratios (HRs) for PFS and OS were calculated using the Cox proportional hazard regression method with both (1) the time to the steroid and SSIA as time-varying covariates and (2) a binary exposure classification not accounting for the time to the treatment. Results: A total of 167 patients were included after matching (132 in the CS cohort and 35 in the CS-SSIA cohort). Sixty-six percent of all the patients had melanoma. The most common irAEs requiring treatment were gastroenterocolitis and hepatitis. In an adjusted analysis not accounting for immortal time bias, there were no significant differences in PFS (HR 0.75, 95% CI [0.46–1.23]) or OS (HR 0.82, 95% CI [0.46–1.47]). In analyses using a time-varying treatment indicator, there was a trend toward improved PFS in patients treated with SSIAs (HR 0.54, CI 0.26–1.10). There was no difference in OS (HR 1.11, CI 0.55–2.23). Patients with melanoma who specifically received infliximab had improved PFS compared to patients with CS only, after adjusting for immortal time bias (HR 0.32, CI 0.24–0.43). Conclusions: The use of SSIAs with CS did not have worse outcomes than CS monotherapy. In melanoma, our findings showed improved PFS for the use of infliximab versus steroid monotherapy for irAEs. Large, prospective, randomized controlled trials are needed to confirm these findings and guide the optimal treatment of irAEs. [ABSTRACT FROM AUTHOR]

Simple Summary: Allogeneic hematopoietic stem cell transplantation (allo-HCT) remains an effective treatment modality in many hematological malignancies. Few studies directly compare rabbit anti-thymocyte globulin (r-ATG) formulations Thymoglobuline (ATG-T) and Grafalon (ATG-G). Our retrospective analysis compared the outcomes in 87 adult allo-HCT patients receiving ATG-T or ATG-G. No significant differences were found in acute graft-versus-host disease (aGvHD) incidence. However, chronic GvHD (cGvHD) was less common with ATG-T (7.5% vs. 38.3%, p = 0.001). ATG-T patients had higher cytomegalovirus (CMV) reactivation rates (70% vs. 31.9%, p < 0.001) and a shorter time to CMV (<61 days, 77.8% vs. 33.3%, p = 0.008), but were mostly asymptomatic (85.7% vs. 43.8%, p = 0.005). Overall survival (OS) and relapse-free survival (RFS) at 5 and 3 years, respectively, showed no significant differences between ATG-T and ATG-G (32.0% vs. 40.3%, p = 0.423; 66.7% vs. 60.4%, p = 0.544). Despite notable advancements in immunotherapy in the past decades, allogeneic hematopoietic stem cell transplantation (allo-HCT) remains a promising, potentially curative treatment modality. Only a limited number of studies have performed a direct comparison of two prevalent rabbit anti-thymocyte globulin (r-ATG) formulations—specifically, Thymoglobuline (ATG-T, formerly Genzyme) and Grafalon (ATG-G, formerly Fresenius). The primary objective of our retrospective analysis was to compare the outcomes of adult patients undergoing matched or mismatched unrelated donor (MUD/MMUD) allo-HCT, with a graft-versus-host disease (GvHD) prophylaxis based on either ATG-T or ATG-G. A total of 87 patients who had undergone allo-HCT between 2012 and 2022 were included. We observed no significant differences between ATG-T and ATG-G concerning the occurrence of acute graft-versus-host disease (aGvHD), regardless of its severity. Conversely, chronic graft-versus-host disease (cGvHD) occurred less frequently in the ATG-T group compared to the ATG-G group (7.5% vs. 38.3%, p = 0.001). The negative impact of ATG-G on cGvHD was confirmed by multivariate analysis (HR 8.12, 95% CI 2.06–32.0, p = 0.003). Patients treated with ATG-T manifested a higher incidence of cytomegalovirus (CMV) reactivations (70% vs. 31.9%, p < 0.001), with a shorter time between transplant and CMV (<61 days, 77.8% vs. 33.3%, p = 0.008) and a higher median CMV copy number (1000 vs. 0, p = 0.004). Notably, despite a higher occurrence of CMV reactivations in the ATG-T cohort, most patients were asymptomatic compared to ATG-G (85.7% vs. 43.8%, p = 0.005). By multivariate analysis, only aGvHD had an influence on CMV reactivations (HR 0.18, 95% CI 0.04–0.75, p = 0.019). Finally, we observed no significant differences in terms of 5-year overall survival (OS) and 3-year relapse-free survival (RFS) while comparing ATG-T and ATG-G (32.0% vs. 40.3%, p = 0.423; 66.7% vs. 60.4%, p = 0.544, respectively). [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer is one of the most commonly diagnosed cancers worldwide with a high probability of developing metastasis over the course of the disease. Only certain patients with colorectal liver metastases can be treated by surgical resection. Different interventional treatments such as laser-induced thermotherapy, microwave ablation, as well as transarterial chemoembolization can be applied for treating colorectal liver metastases. These therapies have been discussed in various studies. However, the current medical literature is still lacking research from large long-term studies. This retrospective monocentric study includes 2140 patients with colorectal liver metastases treated by different locoregional treatments. It is based upon data collected over a period of more than 26 years at the University Hospital Frankfurt of Goethe University. The aim of this study was to analyze the long-term results of different locoregional treatments for colorectal cancer liver metastases (CRLM), including transarterial chemoembolization (TACE), laser-induced thermotherapy (LITT) and microwave ablation (MWA). A total of 2140 patients with CRLM treated at our department between 1993 and 2020 were included in this retrospective study. The patients were divided into the following groups: LITT (573 patients; median age: 62 years), TACE + LITT (346 patients; median age: 62 years), MWA (67 patients; median age: 59 years), TACE + MWA (152 patients; median age: 65 years), and TACE (1002 patients; median age: 62 years). Median survival was 1.9 years in the LITT group and 1.7 years in the TACE + LITT group. The median survival times in the MWA group and TACE + MWA group were 3.1 years and 2.1 years, respectively. The median survival in the TACE group was 0.8 years. The 1-, 3-, and 5-year survival rates were 77%, 27%, and 9% in the LITT group and 74%, 18%, and 5% in the TACE + LITT group, respectively. The corresponding survival rates were 80%, 55%, and 33% in the MWA group, 74%, 36%, and 20% in the TACE + MWA group and 37%, 3%, and 0% in the TACE group, respectively. The long-term results of this study demonstrate the efficacy of locoregional treatments in treating patients with CRLM. The longest survival was found in the MWA group, followed by the combination therapy of TACE and MWA. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal adenoma formation has multiple contributing factors and how these risk factors interact is not precise. Past studies have demonstrated that increased weight is one of the risk factors of colorectal adenoma formation, but does not mean participants with normal body weight are not concerned about colorectal adenoma formation. We aimed to explore the specific risk factors for colorectal adenomas in individuals with normal body weight, who are often overlooked, and the interaction between these risk factors. Background: We aimed to evaluate the interaction between colorectal adenoma risks among asymptomatic individuals in terms of metabolic health status and obesity, and examine the normal waist-to-hip ratio (WHR) in adults with colorectal adenoma risk. Methods: A cross-sectional, retrospective study was conducted at MacKay Memorial Hospital involving 16,996 participants who underwent bidirectional gastrointestinal endoscopy between 2013 and 2023. The study recorded important clinicopathological characteristics, including age, body mass index and WHR, Framingham Risk Score (FRS), blood glucose level, and Helicobacter pylori (H. pylori) infection status. Results: Multivariate logistic regression analysis demonstrated that elevated hemoglobin A1C (HbA1c), increased FRS, positive H. pylori infection, and WHR ≥ 0.9 are independent risk factors for colorectal adenoma. In examining the interaction between FRS and WHR using multivariate logistic regression to evaluate adenoma risk, the OR for the interaction term was 0.95, indicating a decline in adenoma risk when considering the interaction between these two factors. Incorporating HbA1c into the analysis, evaluating the interaction between FRS and WHR still demonstrated a statistically significant impact on adenoma risk (OR 0.96, p < 0.001). Participants with WHR < 0.9, elevated FRS, positive H. pylori infection, and increased HbA1c levels were associated with a higher risk of colorectal adenoma formation. Remarkably, the increased risk of adenoma due to rising HbA1c levels was statistically significant only for those with a WHR < 0.9. Conclusions: An increase in FRS and HbA1c or a positive H. pylori infection still warrants vigilance for colorectal adenoma risk when WHR is 0.9. These factors interacted with each other and were found to have a minimal decline in adenoma risk when considering the interaction between WHR and FRS. [ABSTRACT FROM AUTHOR]

Simple Summary: Identifying the genetic cause of a retinoblastoma tumour can help doctors determine any future cancer risk for the patient or their family. Somatic testing has historically used DNA from the tumour, after the eye has been removed. We and others have previously shown cell-free DNA (cfDNA) from the tumour is present in the eye fluid of retinoblastoma patients. In this study we tested eye fluid from 68 patients, collected at different points in their treatment. Measurable levels of cfDNA were found in all 11 samples of eye fluid taken from patients who had received less than three cycles of chemotherapy, and 95% (21/22) of causal genetic variants were identified. Eye fluid collected later in the treatment had 150 times less cfDNA and only 46% of genetic variants (25/54) could be detected. Eye fluid sampling early in treatment is therefore likely to be required for successful somatic testing in retinoblastoma patients undergoing eye conservation treatment. The identification of somatic RB1 variation is crucial to confirm the heritability of retinoblastoma. We and others have previously shown that, when tumour DNA is unavailable, cell-free DNA (cfDNA) derived from aqueous humour (AH) can be used to identify somatic RB1 pathogenic variation. Here we report RB1 pathogenic variant detection, as well as cfDNA concentration in an extended cohort of 75 AH samples from 68 patients. We show cfDNA concentration is highly variable and significantly correlated with the collection point of the AH. Cell-free DNA concentrations above 5 pg/µL enabled the detection of 93% of known or expected RB1 pathogenic variants. In AH samples collected during intravitreal chemotherapy treatment (Tx), the yield of cfDNA above 5 pg/µL and subsequent variant detection was low (≤46%). However, AH collected by an anterior chamber tap after one to three cycles of primary chemotherapy (Dx1+) enabled the detection of 75% of expected pathogenic variants. Further limiting our analysis to Dx1+ samples taken after ≤2 cycles (Dx ≤ 2) provided measurable levels of cfDNA in all cases, and a subsequent variant detection rate of 95%. Early AH sampling is therefore likely to be important in maximising cfDNA concentration and the subsequent detection of somatic RB1 pathogenic variants in retinoblastoma patients undergoing conservative treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: We studied the feasibility and safety of using bronchoscopically implanted electromagnetic transponders to monitor deep inspiration breath hold (DIBH) for thoracic radiation therapy (RT) of primary lung cancers or lung metastases. Three transponders were implanted near the tumor, followed by CT simulation. The initial gating window was ±5 mm; in a second cohort, the window was incrementally reduced to determine the smallest feasible gating window: this was identified to be ±3 mm. Among the 48 patients enrolled, transponder-guided DIBH was feasible in all but two patients (96% feasible), where it failed because the distance between the transponders and the antenna was >19 cm. Toxicities at least possibly related to transponders or the implantation procedure were grade 2 in six patients, grade 3 in three patients, and grade 4 in one patient. Toxicities at least possibly related to RT were grade 2 in 18 patients and grade 3 in four patients. Transponder-guided DIBH is a feasible and safe approach for delivering thoracic RT. Background: Electromagnetic transponders bronchoscopically implanted near the tumor can be used to monitor deep inspiration breath hold (DIBH) for thoracic radiation therapy (RT). The feasibility and safety of this approach require further study. Methods: We enrolled patients with primary lung cancer or lung metastases. Three transponders were implanted near the tumor, followed by simulation with DIBH, free breathing, and 4D-CT as backup. The initial gating window for treatment was ±5 mm; in a second cohort, the window was incrementally reduced to determine the smallest feasible gating window. The primary endpoint was feasibility, defined as completion of RT using transponder-guided DIBH. Patients were followed for assessment of transponder- and RT-related toxicity. Results: We enrolled 48 patients (35 with primary lung cancer and 13 with lung metastases). The median distance of transponders to tumor was 1.6 cm (IQR 0.6–2.8 cm). RT delivery ranged from 3 to 35 fractions. Transponder-guided DIBH was feasible in all but two patients (96% feasible), where it failed because the distance between the transponders and the antenna was >19 cm. Among the remaining 46 patients, 6 were treated prone to keep the transponders within 19 cm of the antenna, and 40 were treated supine. The smallest feasible gating window was identified as ±3 mm. Thirty-nine (85%) patients completed one year of follow-up. Toxicities at least possibly related to transponders or the implantation procedure were grade 2 in six patients (six incidences, cough and hemoptysis), grade 3 in three patients (five incidences, cough, dyspnea, pneumonia, and supraventricular tachycardia), and grade 4 pneumonia in one patient (occurring a few days after implantation but recovered fully and completed RT). Toxicities at least possibly related to RT were grade 2 in 18 patients (41 incidences, most commonly cough, fatigue, and pneumonitis) and grade 3 in four patients (seven incidences, most commonly pneumonia), and no patients had grade 4 or higher toxicity. Conclusions: Bronchoscopically implanted electromagnetic transponder–guided DIBH lung RT is feasible and safe, allowing for precise tumor targeting and reduced normal tissue exposure. Transponder–antenna distance was the most common challenge due to a limited antenna range, which could sometimes be circumvented by prone positioning. [ABSTRACT FROM AUTHOR]

Simple Summary: Transoral Robotic Surgery (TORS) is increasingly used for various conditions, yet its success and failure remain underexplored. In this multicenter study, we assessed 220 TORS interventions across 211 patients. Success criteria differed by condition, including tumor identification for CUP, resection margins for malignancies, and symptom improvement for benign cases like OSA and chronic lingual tonsillitis. Predictors of success varied, with factors such as patient comorbidity, tumor characteristics, and demographics playing roles. Conversely, failure predictors encompassed postoperative complications and pain, linked to patient health and demographics. These insights into TORS outcomes may aid in patient selection and counseling across different conditions, informing clinical practice and enhancing patient care. Transoral Robotic Surgery (TORS) is utilized for treating various malignancies, such as early-stage oropharyngeal cancer and lymph node metastasis of an unknown primary tumor (CUP), and also benign conditions, like obstructive sleep apnea (OSA) and chronic lingual tonsillitis. However, the success and failure of TORS have not been analyzed to date. In this retrospective observational multicenter cohort study, we evaluated patients treated with TORS using the da Vinci surgical system. Success criteria were defined as identification of the primary tumor for CUP, >2 mm resection margin for malignant conditions, and improvement on respiratory polygraphy and tonsillitis complaints for benign conditions. A total of 220 interventions in 211 patients were included. We identified predictors of success, such as low comorbidity status ACE-27, positive P16 status, and lower age for CUP, and female gender and OSA severity for benign conditions. For other malignancies, no predictors for success were found. Predictors of failure based on postoperative complications included high comorbidity scores (ASA) and anticoagulant use, and for postoperative pain, younger age and female gender were identified. This study provides valuable insights into the outcomes and predictors of success and failure in TORS procedures across various conditions and may also help in patient selection and counseling. [ABSTRACT FROM AUTHOR]

Simple Summary: Nabpaclitaxel plus gemcitabine is the standard of care treatment for advanced pancreatic ductal adenocarcinoma (PDAC), the third leading cause of cancer-related deaths worldwide. This therapy reported improved overall survival in metastatic PDAC. Despite the efficacy of available treatments, the poor outcome for patients with PDAC necessitates the need for novel therapies. In a preclinical study, a neutralizing monoclonal antibody specific to human platelet-derived growth factor receptor alpha (PDGFRα) has proven its efficacy in advanced PDAC. Further, a PDGFRα monoclonal antibody, olaratumab, in combination with chemotherapy demonstrated clinical benefit in patients with soft tissue sarcoma. In light of the above findings, the current trial evaluates the efficacy and safety of olaratumab and nabpaclitaxel plus gemcitabine combination therapy in treatment-naïve patients with metastatic PDAC. However, the combination therapy failed to improve survival outcomes compared with chemotherapy alone. Nevertheless, the safety profile of olaratumab was consistent with the previous studies. The efficacy and safety of olaratumab plus nabpaclitaxel and gemcitabine in treatment-naïve participants with metastatic pancreatic ductal adenocarcinoma was evaluated. An initial phase 1b dose-escalation trial was conducted to determine the olaratumab dose for the phase 2 trial, a randomized, double-blind, placebo-controlled trial to compare overall survival (OS) in the olaratumab arm vs. placebo arms. In phase 1b, 22 participants received olaratumab at doses of 15 and 20 mg/kg with a fixed dose of nabpaclitaxel and gemcitabine. In phase 2, 159 participants were randomized to receive olaratumab 20 mg/kg in cycle 1 followed by 15 mg/kg in the subsequent cycles (n = 81) or the placebo (n = 78) on days 1, 8, and 15 of a 28-day cycle, plus nabpaclitaxel and gemcitabine. The primary objective of the trial was not met, with a median OS of 9.1 vs. 10.8 months (hazard ratio [HR] = 1.05; 95% confidence interval [CI]: 0.728, 1.527; p = 0.79) and the median progression-free survival (PFS) was 5.5 vs. 6.4 months (HR = 1.19; 95% CI: 0.806, 1.764; p = 0.38), in the olaratumab vs. placebo arms, respectively. The most common treatment-emergent adverse event of any grade across both arms was fatigue. Olaratumab plus chemotherapy failed to improve the OS or PFS in participants with metastatic PDAC. There were no new safety signals. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometrial cancer continues to be among the most prevalent cancers affecting the female reproductive system. The timely and precise diagnosis of endometrial cancer is crucial for the survival of individuals affected by it. The aim of the present systematic review and meta-analysis was to consolidate and assess the findings concerning the diagnostic precision of frozen section analysis of endometrial tissues for diagnosing endometrial cancer and atypical hyperplasia. The method has demonstrated high reliability in diagnosing endometrial cancer and even greater accuracy for atypical hyperplasia. This could significantly influence clinical practice, as a less invasive procedure such as frozen section biopsy could benefit a substantial number of women. The early and accurate diagnosis of endometrial cancer is of paramount importance for the survival of these patients. The aim of this study was to systematically appraise the available data regarding the accuracy of frozen section biopsy in diagnosing endometrial cancer. A thorough literature search was performed in PubMed/Medline, Scopus and the Cochrane Central Register of Controlled Trials databases from inception up to January 2023, with the use of specific, relevant key terms. A quality evaluation for each study was performed with the QUADAS-2 tool, whereas a bivariate random-effect model was performed to generate a summary receiver-operated curve. Heterogeneity was evaluated with Cochrane Q and Higgins' I2 statistics. Subgroup analyses were performed for studies focused on atypical hyperplasia and those focused on endometrial cancer. The search yielded 47 studies, involving 7790 patients with endometrial cancer. Among them, only 11 could be included in the quantitative analysis. QUADAS-2 evaluation resulted in rather high quality among the included studies. Quantitative synthesis resulted in a pooled sensitivity of 0.863 and pooled specificity of 0.916. The AUC was 0.948, the Q statistic was 10.488 (10 df, p = 0.399) and Higgins' I2 (4.655%) reported no significant heterogeneity. Subgroup analyses based on the diagnosis revealed a pooled sensitivity 0.886, specificity 0.862 and AUC 0.934 for endometrial cancer versus a sensitivity of 0.816, specificity of 0.962 and AUC 0.939 for atypical hyperplasia. Frozen section appears as a valid and reliable diagnostic tool for endometrial cancer. Its reliability seems to be even higher for the diagnosis of atypical hyperplasia. Therefore, this method may be considered in clinical practice and in settings with appropriate resources. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic neuroendocrine tumors are a rare and heterogenous group of neoplasms. Surgical resection is the only curative option. However, there has been an increase in palliative medical options. The aim of this retrospective study was to investigate responses for the most commonly used medical treatments in 192 patients. The current results support the effectiveness of somatostatin analogues in low-grade tumors and showed that it might also be used in patients with Ki-67 ≥ 10%. Treatment with streptozocin and 5-floururacil as first-line treatment showed good efficacy for G2 disease. Due to good efficacy and generally good tolerability PRRT might be considered as first-line treatment for NET G2. The results confirmed poor prognosis in high-grade tumors treated with carboplatin/etoposide or temozolomide. The current results provide valuable knowledge as current treatment algorithms and sequencing are primarily guided by expert opinions with limited evidence. Background: Given the rarity and heterogeneity of pancreatic neuroendocrine neoplasms (pNEN), treatment algorithms and sequencing are primarily guided by expert opinions with limited evidence. Aim: To investigate overall survival (OS), median progression-free survival (mPFS), and prognostic factors associated with the most common medical treatments for pNEN. Methods: Retrospective single-center study encompassing patients diagnosed and monitored between 2000 and 2020 (n = 192). Results: Median OS was 36 (95% CI: 26–46) months (99 months for grade (G) 1, 62 for G2, 14 for G3, and 10 for neuroendocrine carcinomas). Patients treated with somatostatin analogues (SSA) (n = 59, median Ki-67 9%) had an mPFS of 28 months. Treatment line (HR (first line as reference) 4.1, 95% CI: 1.9–9.1, p ≤ 0.001) emerged as an independent risk factor for time to progression. Patients with a Ki-67 index ≥10% (n = 28) had an mPFS of 27 months. Patients treated with streptozocin/5-fluorouracil (STZ/5FU) (n = 70, first-line treatment n = 68, median Ki-67 10%) had an mPFS of 20 months, with WHO grade serving as an independent risk factor (HR (G1 (n = 8) vs. G2 (n = 57)) 2.8, 95% CI: 1.1–7.2, p-value = 0.031). Median PFS was 21 months for peptide receptor radionuclide therapy (PRRT) (n = 41, first line n = 2, second line n = 29, median Ki-67 8%), 5 months for carboplatin and etoposide (n = 66, first-line treatment n = 60, median Ki-67 80%), and 3 months for temozolomide-based therapy (n = 56, first-line treatment n = 17, median Ki-67 30%). Conclusion: (1) Overall survival was, as expected, highly dependent on grade; (2) median PFS for SSA was around 2.5 years without difference between tumors with Ki-67 above or below 10%; (3) STZ/5FU as first-line treatment exhibited a superior mPFS of 20 months compared to what has historically been reported for targeted treatments; (4) PRRT in G2 pNEN achieved an mPFS similar to first-line chemotherapy; and (5) limited treatment efficacy was observed in high-grade tumors when treated with carboplatin and etoposide or temozolomide. [ABSTRACT FROM AUTHOR]

Simple Summary: There is little evidence about the optimal timing of systemic chemotherapy (SC) in patients treated with cytoreductive surgery (CRS) and HIPEC for colorectal peritoneal metastases (CRC-PM). Due to the lack of evidence in this field, a systematic literature search and a meta-analysis of relevant studies were performed. Twenty-one studies were included in the systematic review and fifteen in the quantitative analysis (4523 patients). Postoperative SC was associated with increased overall survival compared to no SC or a preoperative SC regimen, whereas SC (pre or post) and pre-SC compared to surgery alone were not. Similar results were found for disease-free survival. Preoperative SC was not associated with an increased risk of severe surgical complications. Background. For patients with colorectal cancer (CRC) peritoneal metastases (PM) who are eligible for cytoreductive surgery (CRS), the indication and timing of systemic chemotherapy (SC) are still under debate. This study aims to analyze the role of pre, post or perioperative SC on the survival and surgical complications of patients treated with CRS-HIPEC. Methods. After a systematic search in MEDLINE, Cochrane Database of Systematic Reviews, Scopus, Web of Science and Embase, a meta-analysis was performed to compare postoperative complications, disease-free survival (DFS) and overall survival (OS) according to SC administration and timing. PROSPERO: CRD42023478977. Results. Of 1203 studies screened, 15 were included in the meta-analysis (4523 patients). Post-operative SC was associated with increased overall survival (post-SC vs. no post-SC: HR 0.81, p = 0.00001, I2 = 0%; pre-SC vs. post-SC: HR 0.65, p = 0.01, I2 = 28%), whereas SC (pre or post) or pre-SC compared to surgery alone was not (SC vs. no SC: p = 0.29, I2 = 80%; pre-SC vs. no pre-SC: p = 0.59, I2 = 58%). Similar results were seen for DFS. SC was not associated with an increased complication rate (p = 0.47, I2 = 64%). Conclusions. Systemic chemotherapy administration in patients undergoing radical surgery for colorectal peritoneal metastases is associated with increased survival only in the adjuvant/post-operative setting. Considering the limitations of the included studies, further trials are needed to answer this unresolved question. [ABSTRACT FROM AUTHOR]

Simple Summary: Magnetic resonance imaging (MRI) can be used for the preoperative local staging of endometrial cancer (EC). The purpose of this study was to assess the performance of MRI for the detection of ≥pT1b disease (i.e., tumor invasion in ≥50% of the myometrium, into the cervical stroma or spread outside the uterus) and to evaluate whether tumor size measured via MRI was predictive for ≥pT1b disease, independent of imaging signs of invasion. We found that MRI had good performance for the detection of ≥pT1b disease and that a tumor diameter of ≥40 mm and a tumor volume of ≥20 mL were highly predictive for the presence of ≥pT1b disease. Our results support the use of MRI in the preoperative staging of EC and suggest including size criteria in EC staging guidelines. Magnetic resonance imaging (MRI) can be used for the preoperative local staging of endometrial cancer (EC). The presence of ≥pT1b disease (i.e., tumor invasion in ≥50% of the myometrium, into the cervical stroma or spread outside the uterus) has important prognostic value and implications for the decision to perform lymphadenectomy. The purpose of this study was to assess the performance of MRI for the detection of ≥pT1b disease and to evaluate whether tumor size measured via MRI was predictive for ≥pT1b disease, independent of imaging signs of deep invasion. MRI T-staging and tumor diameter and volume were correlated with histopathology of the hysterectomy specimen in 126 patients. MRI had a sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 70.0%, 83.3%, 79.2%, 75.3% and 77.0%, respectively, for the detection of ≥pT1b disease. A tumor diameter of ≥40 mm and volume of ≥20 mL measured via MRI were predictive for ≥pT1b disease at rates of 78.3% and 87.1%, respectively. An EC size of at least 5 mm upon MRI was predictive for ≥pT1b disease in more than 50% of cases. Our results support the use of MRI in the preoperative staging of EC and suggest including size criteria in EC staging guidelines. [ABSTRACT FROM AUTHOR]

Simple Summary: Sleep is a fundamental human need. Good-quality sleep has a protective role that allows people to carry out daily activities adequately, ensuring well-being. Prolonged wakefulness causes a wide spectrum of disabilities. This study aims to understand the effects of sleep complaints on health and quality of life for cancer patients, and it has been conducted through the creation of questionnaires for patients to investigate the potential alteration of the sleep pattern. The results obtained may serve as the foundation for designing awareness campaigns, providing information, and updating patients, healthcare personnel, and caregivers. It is definitively important, in fact, to begin an evaluation of the negative effects of sleep complaints in the field of cancer. The model developed can also be replicated in different clinical settings: data adjustment by different parameters (i.e., geographic locations, age, sex, and gender) can be the key to improving the patient's quality of life. Sleep is a fundamental human need; sleep disruption, in fact, causes an increase in the activity of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, metabolic effects, changes in circadian rhythms, and pro-inflammatory responses. The scientific literature is finally starting to pay attention to the central role of sleep alterations in patients health. Oxaliplatin is extensively used for the treatment of gastrointestinal cancer and other malignancies, with an increased frequency of use in recent years. This study aims to understand the effects of sleep complaints on health and quality of life in cancer patients treated with oxaliplatin. A study has been conducted through the creation and distribution of questionnaires to patients to investigate their complaints about sleep quality. We observed significant differences between males and females in evaluating sleep hygiene scores, the Pittsburgh Sleep Quality Index, and previous difficulty sleeping. Moreover, in females, stress, worries, and anxiety seem to play a negative role in the sleep hygiene score. The obtained results could improve the interest of healthcare personnel and caregivers in sleep quality in patients undergoing chemotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Ablative radiotherapy for central early stage non-small cell lung cancer (NSCLC) is controversial in its feasibility and optimal dose prescription due to the risk of severe pneumonia and adverse events associated with mediastinal organs. Carbon-ion radiotherapy (CIRT) is a promising modality of radiotherapy with steep and linear dose distribution and high biological efficacy. We retrospectively analyzed the long-term results of ablative CIRT using 68.4 Gy in 12 fractions for central early stage NSCLC. Irradiation doses to lungs and mediastinal organs such as bronchus and esophagus were controlled and no serious mediastinal organ-related adverse events occurred. In addition, the efficacy was not inferior to that reported in previous studies, including photon SBRT or proton radiotherapy. This means that our CIRT regimen is expected to have a relatively high safety profile for central NSCLC with tumor and organ at risk (OAR) proximity. The aim of this study is to assess the efficacy and safety of ablative carbon ion radiotherapy (CIRT) for early stage central non-small cell lung cancer (NSCLC). We retrospectively reviewed 30 patients who had received CIRT at 68.4 Gy in 12 fractions for central NSCLC in 2006–2019. The median age was 75 years, and the median Karnofsky Performance Scale score was 90%. All patients had concomitant chronic obstructive pulmonary disease, and 20 patients (67%) were considered inoperable. In DVH analysis, the median lung V5 and V20 were 15.5% and 10.4%, and the median Dmax, D0.5cc, D2cc of proximal bronchial tree was 65.6 Gy, 52.8 Gy, and 10.0 Gy, respectively. At a median follow-up of 43 months, the 3-year overall survival, disease-specific survival, and local control rates were 72.4, 75.8, and 88.7%, respectively. Two patients experienced grade 3 pneumonitis, but no grade ≥3 adverse events involving the mediastinal organs occurred. Ablative CIRT is feasible and effective for central NSCLC and could be considered as a treatment option, especially for patients who are intolerant of other curative treatments. [ABSTRACT FROM AUTHOR]

Simple Summary: In clinical practice, human epidermal growth factor receptor (HER2)-negative tumors include triple-negative or luminal breast cancer. HER2-negative breast cancer can be further characterized by immunohistochemical (IHC) and in situ hybridization (ISH) scores into HER2 IHC0 or HER2-low (IHC 1+, 2+/ISH−. Interest in HER2-low tumors has increased as data show the efficacy of HER2-targeted therapies in this subgroup. While several studies have examined treatment variations in the overall breast cancer population, there is limited information on the real-world treatment patterns among patients with HER2 (IHC0/-low) metastatic or recurrent breast cancer. Our study addresses this gap by analyzing treatment and outcomes by HER2 status and found that outcomes were similar in the HER2 IHC0 and -low groups. Our findings add value to the general understanding of the clinical differences between HER2 IHC0/-low and de novo/recurrent disease and have important implications for new effective treatment strategies designed for varying levels of HER2 expression. Improved understanding of the biological heterogeneity of breast cancer (BC) has facilitated the development of more effective and personalized approaches to treatment. This study describes real-world evidence on treatment patterns and outcomes for a population-based cohort of patients with human epidermal growth factor receptor (HER2) IHC0 and -low BC with de novo or recurrent disease from Alberta, Canada. Patients 18+ years old diagnosed with HER2 IHC0/-low, de novo/recurrent BC from 2010 to 2019 were identified using Alberta's cancer registry. Analyses of these patients' existing electronic medical records and administrative claims data were conducted to examine patient characteristics, treatment patterns, and survival outcomes. A total of 3413 patients were included in the study, of which 72.10% initiated first line hormonal and non-hormonal systemic therapy. The 1-year overall survival (OS) was 81.09% [95% CI, 79.52–82.69]. Recurrent patients had a higher OS compared to de novo patients: 54.30 months [95% CI, 47.80–61.90] vs. 31.5 months [95% CI, 28.40–35.90], respectively. Median OS was 43.4 months [95% CI, 40.70–47.10] and 35.80 months [95% CI, 29.00–41.70] among patients with HER2-low and HER2 IHC0 cancer, respectively. The study results provide real-world evidence regarding the clinical outcomes of HER2 IHC0/-low and de novo/recurrent disease. [ABSTRACT FROM AUTHOR]

Simple Summary: The efficacy of abiraterone plus prednisolone (ABI) against nonmetastatic castration-resistant prostate cancer (CRPC) remains unclear. To evaluate enzalutamide and ABI as the first-line treatment for CRPC, we conducted the randomized controlled trial including both metastatic and nonmetastatic CRPC. As a sub-analysis, we focused on nonmetastatic CRPC in this study. ABI and enzalutamide had similar efficacy and safety profiles in patients with nonmetastatic CRPC. Enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) can improve the survival of patients with castration-resistant prostate cancer (CRPC). However, the agent that is more effective against nonmetastatic CRPC remains unclear. To evaluate the agent that can be used as the first-line treatment for CRPC, an investigator-initiated, multicenter, randomized controlled trial (ENABLE Study for PCa) including both metastatic and nonmetastatic CRPC was conducted in Japan. The prostate-specific antigen (PSA) response rate, overall survival, some essential survival endpoints, and safety of patients with nonmetastatic CRPC were also analyzed. In this subanalysis, 15 and 26 patients in the ENZ and ABI arms, respectively, presented with nonmetastatic CRPC. There was no significant difference in terms of the PSA response rate between the ENZ and ABI arms (80% and 64%, respectively; p = 0.3048). The overall survival did not significantly differ between the two arms (HR: 0.68; 95% CI: 0.22–2.14, p = 0.5260). No significant differences were observed in terms of radiographic progression-free survival and cancer-specific survival between the ENZ and ABI arms (HR: 0.81; 95% CI: 0.35–1.84; p = 0.6056 and HR: 0.72; 95% CI: 0.19–2.73; p = 0.6443, respectively). Only four and six patients in the ENZ and ABI arms, respectively, had ≥grade 3 adverse events. ABI and ENZ had similar efficacy and safety profiles in patients with nonmetastatic CRPC. [ABSTRACT FROM AUTHOR]

Simple Summary: Head and neck bone reconstruction with revascularized free periosteal flaps and scaffold is an overlooked option in the literature. Aim of the present paper was to systematically analyse the results of maxillary and mandibular reconstruction with this technique. We found a total of 7 studies with 55 patients fitting with our inclusion criteria. The overall rate of complications was 43.7%. The success rate intended as scaffold integration resulted to be 74.5%. Our paper therefore highlighted that maxillary and mandibular reconstruction with revascularized free periosteal flaps and scaffold is a possible alternative in patient unable to bone free flap complex reconstruction, with a success rate higher to that of other secondary options. Introduction: Head and neck bone reconstruction is a challenging surgical scenario. Although several strategies have been described in the literature, bone free flaps (BFFs) have become the preferred technique for large defects. Revascularized free periosteal flaps (FPFs) with support scaffold represents a possible alternative in compromised patient, BFF failure, or relapsing cancers as salvage treatment. However, only few clinical applications in head and neck are reported in literature. Purpose of the study was to systematically analyse the results of functional and oncologic maxillary and mandibular reconstruction with FPF with scaffold. Materials and Methods: A comprehensive review of the dedicated literature was performed according to the PRISMA guidelines searching on Scopus, PubMed/MEDLINE, Cochrane Library, Embase, Researchgate and Google Scholar databases using relevant keywords, phrases and medical subject headings (MeSH) terms. An excursus on the most valuable FPF' harvesting sites was also carried out. Results: A total of 7 studies with 55 patients were included. Overall, the majority of the patients (n = 54, 98.1%) underwent an FPF reconstruction of the mandibular site. The most used technique was the radial forearm FPF with autologous frozen bone as scaffold (n = 40, 72.7%). The overall rate of complications was 43.7%. The success rate intended as scaffold integration resulted to be 74.5%. Conclusions: Maxillary and mandibular reconstruction with FPF and scaffold is a possible alternative in patient unfit for complex BFF reconstruction and it should be considered as a valid alternative in the sequential salvage surgery for locally advanced cancer. Moreover, it opens future scenarios in head and neck reconstructive surgery, as a promising tool that can be modelled to tailor complex 3D defects, with less morbidities to the donor site. [ABSTRACT FROM AUTHOR]

Simple Summary: For centrally located non-small cell lung cancer (NSCLC), sleeve lobectomy would be preferable to pneumonectomy (PN). In this context, however, the role of complex sleeve lobectomy (CLS) is still poorly understood. Our study compared CLS with PN using a retrospective analysis. Research shows that CLS has a lower 90-day mortality rate and fewer major complications compared to PN, while oncological outcomes remain comparable. These results support the contention that CLS is a safe and effective procedure for centrally located NSCLC, even after neoadjuvant treatment. Background: Standard sleeve lobectomies are recommended over pneumonectomy (PN), but the efficacy and oncological proficiency of complex sleeve lobectomies (CSLs) have not been completely investigated. The aim of this study was to report our experience in CSL in patients affected by a centrally located non-small-cell lung cancer (NSCLC), comparing all the variables and outcomes with PN. Methods: From 2014 to 2022, we collected the data of patients who underwent PN and CSL for NSCLC, excluding neuroendocrine tumors, salvage surgery or carinal resection. Regression analysis was used to assess the association between procedures and complications; the Kaplan–Meier method and Cox regression analysis were used to evaluate survival and risk factors of reduced survival. Results: We analyzed n = 38 extended sleeve lobectomies and n= 6 double-sleeve lobectomies (CSL group) and n= 60 PNs. We had a trend toward higher postoperative mortality in the PN group (5% vs. 0%, p = 0.13). Major complications and bronchial fistula developed in 21.7% and 6.8% (p = 0.038) and in 6.7% and 4.5% (p = 0.64), respectively. The right side was identified as risk factor for major complications, whereas age > 70 and PN had a trend of association in multivariable analysis. The median OS was similar between the two groups (p = 0.76) and cancer recurrence was the only significant risk factors of reduced OS. Excluding functionally compromised patients, the OS of CSL was better than that of PN (67% vs. 42%, p = 0.25). Conclusions: Considering that major complications are often associated with mortality after surgery for centrally located NSCLC, CSLs could be considered an alternative to PN while also ensuring comparable survival. [ABSTRACT FROM AUTHOR]

Simple Summary: Local recurrence is a significant issue for advanced gastric cancer patients. Complete mesogastric excision (CME) has been advocated to enhance lymph node (LN) retrieval and reduce recurrence rates. A systematic review of the literature was conducted according to the Cochrane recommendations, and meta-analyses of means and binary outcomes were developed. The number of lymph nodes retrieved was the primary endpoint, with other postoperative outcomes as secondary. Thirteen studies were included, showing that the mean number of harvested LNs was significantly higher among patients undergoing CME. CME patients also had significantly lower intraoperative blood loss, a shorter length of stay, and a shorter operative time. Radical gastrectomy with CME may provide a safe and more radical lymphadenectomy. Long-term outcomes and the applicability of this technique in the West are still to be proven. Complete mesogastric excision (CME) has been advocated to allow for a more extensive retrieval of lymph nodes, as well as lowering loco-regional recurrence rates. This study aims to analyze the short-term outcomes of D2 radical gastrectomy with CME compared to standard D2 gastrectomy. A systematic review of the literature was conducted according to the Cochrane recommendations until 2 July 2023 (PROSPERO ID: CRD42023443361). The primary outcome, expressed as mean difference (MD) and 95% confidence intervals (CI), was the number of harvested lymph nodes (LNs). Meta-analyses of means and binary outcomes were developed using random effects models to assess heterogeneity. The risk of bias in included studies was assessed with the RoB 2 and ROBINS-I tools. There were 13 studies involving 2009 patients that were included, revealing a significantly higher mean number of harvested LNs in the CME group (MD: 2.55; 95% CI: 0.25–4.86; 95%; p = 0.033). The CME group also experienced significantly lower intraoperative blood loss, a lower length of stay, and a shorter operative time. Three studies showed a serious risk of bias, and between-study heterogeneity was mostly moderate or high. Radical gastrectomy with CME may offer a safe and more radical lymphadenectomy, but long-term outcomes and the applicability of this technique in the West are still to be proven. [ABSTRACT FROM AUTHOR]

Simple Summary: Pazopanib is an oral drug for metastatic pretreated uterine leiomyosarcoma that received approval in 2012, but poor data have been reported on its activity in real life since the disease is very rare. Uterine leiomyosarcoma has a poor objective response rate to other agents. We assessed the effectiveness and safety of pazopanib in everyday clinical practice, showing its activity and tolerability in patients. Background: Uterine leiomyosarcoma (uLMS) is characterized by aggressive behavior associated with a high risk of relapse and mortality. Several therapeutic agents have been employed in the treatment of metastatic disease, with a poor objective response rate. Pazopanib, approved in 2012, is a multi-targeted, orally active small molecule that exerts its effects by inhibiting several tyrosine kinases. To date, poor research on real-life data has been conducted. We aimed to assess the effectiveness and safety of the drug in everyday clinical practice. Methods: We present results of multicenter retrospective data on 38 patients with heavily pretreated metastatic uLMS who underwent oral pazopanib during their therapeutic journey. Results: At a median follow-up of 8.6 months, the disease control rate was 55.2%, with 17% partial responses and 15 patients (39.5%) with stable disease. At a median follow-up of 8.6 months, median progression-free survival was 4 months, and median overall survival was 19.8 months. The most common grade 3 adverse events (AEs) drug-related were hepatic toxicities, diarrhea, hypertension, nausea, and vomiting (all of them with an incidence of 5% considering the whole study cohort). No grade 4 AEs occurred. Conclusions: Pazopanib in everyday clinical practice is safe and shows a good disease control rate with prolonged survival. [ABSTRACT FROM AUTHOR]

Simple Summary: There are limited studies comparing selpercatinib to standard treatments in previously treated patients with certain solid cancers that have alterations in the RET receptor. The aim of this post hoc comparative effectiveness analysis study was to compare investigator-assessed outcomes among patients with RET-altered solid tumors who were treated with selpercatinib but naïve to standard therapies versus those previously treated with only standard therapies. This study showed that selpercatinib use as frontline therapy is associated with improved outcomes versus standard therapies in patients with RET-altered cancers in the lung, thyroid, and other non-lung, non-thyroid organs in the body. Selpercatinib use was associated with a significantly lower risk of treatment discontinuation, starting a new systemic treatment (or death), or disease progression compared to standard therapies. Selpercatinib is indicated for locally advanced/metastatic RET-activated solid tumors after progression or following prior systemic therapies. Until the recently published data from LIBRETTO-431 and LIBRETTO-531, there were limited effectiveness data comparing selpercatinib with other first-line treatments in RET-activated non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC), and thyroid cancer (TC). This study analyzed patient data from LIBRETTO-001 and compared the outcomes (time to treatment discontinuation {TTD}, time to next treatment or death {TTNT-D}, time to progression {TTP}, and the objective response rate {ORR}) of first-line selpercatinib (selpercatinib arm) use with the outcomes of first-line standard therapies in patients who then received selpercatinib in later lines of treatment (comparator arm). Overall, the first-line selpercatinib arm had a longer TTD, TTNT-D, and TTP versus the first-line comparator arm. The hazard ratios (HRs) for TTD were 0.29 (NSCLC), 0.15 (MTC), 0.08 (TC); for TTNT-D, the HRs were 0.48 (NSCLC), 0.11 (MTC), 0.09 (TC); and for TTP, the HRs were 0.54 (NSCLC), 0.15 (MTC), and 0.12 (TC). The ORR was higher for first-line selpercatinib versus the first-line comparator (NSCLC: 85.3% vs. 39.7%; MTC: 82.6% vs. 15.2%; and TC: 81.8% vs. 31.8%). First-line selpercatinib use is associated with improved outcomes compared to first-line comparator therapies for patients with advanced/metastatic RET-activated cancers. [ABSTRACT FROM AUTHOR]

Simple Summary: Liver transplantation is emerging as a treatment option for patients with colorectal liver metastases. Due to the lack of liver donors, patient selection is vital. In this study, we report on the predictive value of combining metabolic tumor volume obtained from the pre-transplantation 18F-FDG PET/CT with the radiological measurements of tumor load (size, number, and tumor burden score) to select patients with the probability of long-term survival. Patients with low metabolic tumor volume have long disease-free survival, overall survival, and survival after relapse despite a high number of liver metastases and a high tumor burden score. This underlines the prognostic properties of metabolic active-tumor burden beyond conventional measurements. The aim of the present study is to report on the ability of metabolic tumor volume (MTV) of liver metastases from pre-transplant 18F-FDG PET/CT in combination with conventional radiological measurements from CT scans to predict long-term disease-free survival (DFS), overall survival (OS), and survival after relapse (SAR) after liver transplantation for colorectal liver metastases. The total liver MTV was obtained from the 18F-FDG PET/CT, and the size of the largest metastasis and the total number of metastases were obtained from the CT. DFS, OS, and SAR for patients with a low and high MTV, in combination with a low and high size, number, and tumor burden score, were compared using the Kaplan–Meier method and log–rank test. Patients with a low number of metastases and low MTV had a significantly longer OS than those with a high MTV, with a median survival of 151 vs. 26 months (p = 0.010). Patients with a high number of metastases and low MTV had significantly longer DFS, OS, and SAR than patients with a high MTV (p = 0.034, 0.006, and 0.026). The tumor burden score of group/zone 3, in combination with a low MTV, had a significantly improved DFS, OS, and SAR compared to those with a high MTV (p = 0.034, <0.001, and 0.006). Patients with a low MTV of liver metastases had a long DFS, OS, and SAR despite a high number of liver metastases and a high tumor burden score. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of this review was to evaluate the feasibility and the effectiveness of radiation therapy combined with local tumor ablation therapy in the treatment of primary and recurrent lung cancer in terms of toxicity profile and local control rate. Six studies featuring a total of 115 patients and 119 lesions were selected, showing encouraging outcomes that appear to be promising in terms of toxicity profile. Further prospective studies are need to better delineate combining LTA-RT treatment benefits in this setting. In patients with early-stage or recurrent NSCLC who are unable to tolerate surgery, a benefit could derive only from a systemic therapy or another few forms of local therapy. A systematic review was performed to evaluate the feasibility and the effectiveness of radiotherapy combined with local ablative therapies in the treatment of primary and recurrent lung cancer in terms of toxicity profile and local control rate. Six studies featuring a total of 115 patients who met eligibility criteria and 119 lesions were included. Three studies evaluated lung cancer patients with a medically inoperable condition treated with image-guided local ablative therapies followed by radiotherapy: their local control rate (LC) ranged from 75% to 91.7% with only 15 patients (19.4%) reporting local recurrence after combined modality treatment. The other three studies provided a salvage option for patients with locally recurrent NSCLC after RT: the median follow-up period varied from 8.3 to 69.3 months with an LC rate ranging from 50% to 100%. The most common complications were radiation pneumonitis (9.5%) and pneumothorax (29.8%). The proposed intervention appears to be promising in terms of toxicity profile and local control rate. Further prospective studies are need to better delineate combining LTA-RT treatment benefits in this setting. [ABSTRACT FROM AUTHOR]

Simple Summary: On rare occasions, a handful of innovative cancer drugs may successfully go through clinical trials and manage to obtain simultaneous regulatory approvals to treat a specific disease, providing hope for improved treatment outcomes. In the past few years, physicians in North America, Europe, and other countries with stronger economies have been able to use several of the recently approved drugs to treat a blood cancer called multiple myeloma, once older therapies have failed. This study looked at the treatment outcomes associated with the wave of newer drugs in patients diagnosed with multiple myeloma in Greece. The results showed that approximately three-quarters of patients who received one of the newer drugs after having progressed on front-line therapies remained in remission a year after initiating treatment. This finding was comparable to the results from previous studies in Greek patients who were diagnosed with relapsed or refractory multiple myeloma and had previously used other therapies. Newer methodologies are needed to assess the real-world comparative effectiveness of a "generation" of pharmaceutical innovation versus the prior standard of care. This chart review study aimed to first evaluate the cumulative clinical benefits of pharmaceutical innovation in everyday relapse/refractory multiple myeloma before analyzing findings in the context of respective real-world outcomes from the bortezomib/lenalidomide era. Study endpoints included the 52-week PFS rate in second and third line of therapy (LOT), mPFS-2 across the first and second LOT, the ORR, reasons for discontinuation, and the treatment duration per therapeutic algorithm. Data from 107 patients were collected. The median follow-up was 2.0 years. Of the subjects who met the selection criteria for the second LOT, 72.2% maintained the PFS at 52 weeks. In the third-line setting, the PFS rate at 52 weeks was 63.5%. The mPFS across the first and second, the second, and the third LOTs were 26, 17, and 15 months, respectively. The ORR was 76.1% in the second and 69.7% in the third LOT. After non-response or progression, the main reason for drug discontinuation was treatment intolerability. The second-line ORR and the 52-week PFS rate were similar to previous real-world findings from the bortezomib/lenalidomide era. The cumulative mPFS across the second and third LOTs was higher than the respective mPFS across the first and second LOTs. Despite its limitations, the methodology and findings from this study may be used in future clinical and economic evaluations across all hematological malignancies. [ABSTRACT FROM AUTHOR]

Simple Summary: Third-line or further treatments are rarely given to patients with refractory mCRC. In this regard, two noteworthy innovative therapy options, with varying toxicity profiles and statistically significant improvements in overall survival (OS), progression-free survival (PFS), and disease control, are regorafenib (R) and trifluridine/tipiracil (T). This study is a subset analysis of a larger retrospective study that we have already published, with the aim of evaluating patient outcomes when R and T were administered in that order. The purpose of this analysis was to evaluate the relationship between survival outcomes and the first drug treatment duration (<3 months, 3 to <6 months, and ≥6 months) in patients who had received the regorafenib-to-trifluridine/tipiracil sequence or vice versa. Our substudy found that administering R three to six months prior to T can prolong both OS and PFS in comparison to the opposite sequence. Background: Patients with refractory metastatic colorectal cancer (mCRC) rarely receive third-line or further treatment. In this context, regorafenib (R) and trifluridine/tipiracil (T) are two important novel therapeutic choices with statistically significant increases in overall survival (OS), progression-free survival (PFS), and disease control, with different toxicity profiles. This study is a subgroup analysis of our larger retrospective study, already published, whose objective was to assess the outcomes of patients when R and T were given sequentially. Patients and Methods: The study involved thirteen Italian cancer centers on a 10-year retrospective observation (2012–2022). In this subgroup analysis, we focused our attention on the correlation between the first drug treatment duration (<3 months, 3 to <6 months and ≥6 months) and survival outcomes in patients who had received the sequence regorafenib-to-trifluridine/tipiracil, or vice versa. Results: The initial study included 866 patients with mCRC who received sequential T/R, or R/T, or T or R alone. This analysis is focused on evaluating the impact of the duration of the first treatment in the sequence on clinical outcomes (OS, PFS) and includes 146 and 116 patients of the T/R and R/T sequences, respectively. Based on the duration of the first drug treatment, subgroups for the T/R sequence included 27 patients (18.4%) who received T for <3 months, 86 (58.9%) treated for 3 to <6 months, and 33 (22.6%) treated for ≥6 months; in the reverse sequence (R as the first drug), subgroups included 18 patients (15.5%) who received their first treatment for <3 months, 62 (53.4%) treated for 3 to <6 months, and 35 (31.0%) treated for ≥6 months. In patients who received their first drug treatment for a period of 3 to <6 months, the R/T sequence had a significantly longer median OS (13.7 vs. 10.8 months, p = 0.0069) and a longer median PFS (10.8 vs. 8.5 months, p = 0.0003) than the T/R group. There were no statistically significant differences between groups with first drug treatment durations of <3 months and ≥6 months. Conclusions: Our analysis seems to suggest that the administration of R for a period of 3 to <6 months before that of T can prolong both OS and PFS, as compared to the opposite sequence. [ABSTRACT FROM AUTHOR]

Simple Summary: Preoperative chemoradiation (CRT) for rectal cancer with the intensification of radiotherapy (RT) using dose escalation to the tumor volume has been shown effective in improving tumor regression with high compliance to treatment and low toxicity rates. Most dose-escalation trials used conventional 3D conformal RT with concurrent capecitabine. More recently, phase I-II trials investigated intensified RT programs with advanced intensity-modulated RT and simultaneous boost (IMRT-SIB) supported by image-guided RT (IGRT) techniques, highlighting their feasibility and promising activity. However, only limited data on long-term outcomes are available. We analyzed the long-term results of a retrospective, multicenter experience with preoperative capecitabine-based CRT intensification with IMRT-SIB in real-life clinical practice in 10 Italian institutions. The use of moderate IMRT-SIB dose intensification with a full dose of concurrent capecitabine was safe and well tolerated. In addition, an organ preservation strategy has been shown feasible in carefully selected, responsive patients with a promising long-term rectal preservation rate. Long-term local control, progression-free and overall survival rates compared favorably with conventional CRT trials. Given the higher incidence of distant metastases in the subset of high-risk patients, the incorporation of IMRT-SIB and capecitabine with a more effective systemic therapy component may represent a new area of investigational interest while the use of IMRT-SIB and capecitabine in a primarily organ-preservation strategy may be a valuable option for low-intermediate-risk patients. Background: Despite the feasibility and promising activity data on intensity-modulated RT and simultaneous integrated boost (IMRT-SIB) dose escalation in preoperative chemoradiation (CRT) for locally advanced rectal cancer (LARC), few data are currently available on long-term outcomes. Patients and Methods: A cohort of 288 LARC patients with cT3-T4, cN0-2, cM0 treated with IMRT-SIB and capecitabine from March 2013 to December 2019, followed by a total mesorectal excision (TME) or an organ-preserving strategy, was collected from a prospective database of 10 Italian institutions. A dose of 45 Gy in 25 fractions was prescribed to the tumor and elective nodes, while the SIB dose was prescribed according to the clinical practice of each institution on the gross tumor volume (GTV). Concurrent capecitabine was administered at a dose of 825 mg/m2 twice daily, 7 days a week. The primary objective of the study was to evaluate long-term outcomes in terms of local control (LC), progression-free survival (PFS) and overall survival (OS). The secondary objective was to confirm the previously reported feasibility, safety and efficacy (pCR, TRG1-2 and downstaging rates) of the treatment in a larger patient population. Results: All patients received a dose of 45 Gy to the tumor and elective nodes, while the SIB dose ranged from 52.5 Gy to 57.5 Gy (median 55 Gy). Acute gastrointestinal and hematologic toxicity rates of grade 3–4 were 5.7% and 1.8%, respectively. At preoperative restaging, 36 patients (12.5%) with complete or major clinical responses (cCR or mCR) were offered an organ-preserving approach with local excision (29 patients) or a watch and wait strategy (7 patients). The complete pathologic response rate (pCR) in radically operated patients was 25.8%. In addition, 4 TME patients had pT0N1 and 19 LE patients had pT0Nx, corresponding to an overall pT0 rate of 31.3%. Of the 36 patients selected for organ preservation, 7 (19.5%) required the completion of TME due to unfavorable pathologic features after LE or tumor regrowth during W-W resulting in long-term rectal preservation in 29 of 288 (10.1%) of the total patient population. Major postoperative complications occurred in 14.2% of all operated patients. At a median follow-up of 50 months, the 5-year PFS and OS rates were 72.3% (95% CI: 66.3–77.4) and 85.9% (95% CI: 80.2–90.1), respectively. The 5-year local recurrence (LR) rate was 9.2% (95% CI: 6.0–13.2), while the distant metastasis (DM) rate was 21.3% (95% CI: 16.5–26.5). The DM rate was 24.5% in the high-risk subset compared to 16.2% in the low-intermediate risk group (p = 0.062) with similar LR rates (10% and 8%, respectively). On multivariable analysis, cT4 and TRG3–5 were significantly associated with worse PFS, OS and metastasis-free survival. Conclusions: Preoperative IMRT-SIB with the moderate dose intensification of 52.5–57.5 Gy (median 55 Gy) and the full dose of concurrent capecitabine confirmed to be feasible and effective in our real-life clinical practice. Organ preservation was shown to be feasible in carefully selected, responsive patients. The favorable long-term survival rates highlight the efficacy of this intensified treatment program. The incorporation of IMRT-SIB with a more effective systemic therapy component in high-risk patients could represent a new area of investigational interest. [ABSTRACT FROM AUTHOR]

Simple Summary: The main treatment for extramammary Paget's disease (EMPD) is still surgery, but this neoplasm usually spreads beyond the clinical surroundings of the lesion, and achieving histopathologically free margins can be challenging and requires mutilating surgery. Moreover, the recurrence rate of the disease is high, reflecting its multifocal nature. Topical immunotherapy could be an alternative treatment for EMPD. The aim of this systematic review was to assess the effectiveness of topical imiquimod in the clinical response of EMPD patients and to describe the management of topical imiquimod in EMPD. Learning about non-surgical treatments such as topical imiquimod can help clinicians manage EMPD and find a balance between disease resolution and treatment morbidity. Extramammary Paget's disease (EMPD) is subclinical in extent and multifocal in nature. There is no global consensus for treatment, so its management represents a challenge in clinical practice. Therefore, we conducted a systematic review through the main electronic databases to assess the effectiveness of topical imiquimod in cutaneous EMPD and to discuss its management. Finally, 24 studies involving a total of 233 EMPD patients treated with topical imiquimod were selected. The topical imiquimod response rate was 67%, and the complete response (CR) rate was 48%. Patients were treated with a three–four times a week regimen in most cases, ranging between 2 to 52 weeks. In addition, imiquimod was applied as an adjunctive treatment in 21 patients, achieving a CR rate of 71%. Consequently, imiquimod therapy could achieve a good response ratio as a first-line treatment, as adjuvant and neo-adjuvant therapy, and as a treatment for recurrent disease. The heterogeneity between studies and the lack of a control arm made it impossible to conduct a meta-analysis. To improve the quality of evidence on EMPD, multicenter studies are essential to collect a larger number of patients and, consequently, obtain high-quality evidence to standardize treatment. The Prospero registration number is CRD42023447443. [ABSTRACT FROM AUTHOR]

Simple Summary: This study evaluates the impact of treatment sequencing on the outcomes of patients with chronic lymphocytic leukemia. By analyzing data from patients treated at the Fondazione Policlinico Universitario Agostino Gemelli IRCCS in Rome, we showed how the sequence of therapies has evolved over the years in first-line and relapsed/refractory patients and how this change in the treatment paradigm has affected survival. In addition, the poor outcome of patients exposed to cBTKi and BCL2i raises the question of what the best approach might be for treating high-risk patients. Background: This monocentric retrospective study describes the treatment patterns and outcomes of chronic lymphocytic leukemia (CLL) patients. Methods: Adult CLL patients treated between 1992 and 2022 were included. The time to next treatment (TTNT) was defined as the time from the treatment's start to the start of a subsequent therapy or death. The time to next treatment failure or death (TTNTF) was defined as the time from treatment discontinuation to the discontinuation of a subsequent therapy or death. Results: Of 637 registered patients, 318 (49.9%) received treatment. We evaluated 157 cBTKi-exposed, 34 BCL2i-exposed cBTKi-naïve, and 26 double-exposed patients. The five-year TTNT values in the cBTKi-exposed patients were 80% (median NR), 40% (median 40 months), and 21% (median 24 months) months in the first line (1L), second line (2L), and beyond the second line (>2L), respectively (p < 0.0001). The five-year TTNT values in the BCL2i-exposed patients were 83% (median NR), 72% (median NR), 12% (median 28 months) in the 1L, 2L, and >2L, respectively (p = 0.185). The median TTNTF was 9 months (range 1–87) after cBTKi and 17 months (range 8–49) after both a cBTKi and BCL2i. Conclusions: This study suggests that, in CLL patients, the earlier we used targeted therapies, the better was the outcome obtained. Nonetheless, the poor outcomes in the advanced lines of therapy highlight the need for more effective treatments. [ABSTRACT FROM AUTHOR]

Simple Summary: Although body composition-related biomarkers are associated with the prognosis of patients with cancer, whether they are associated with the therapeutic effects of immune checkpoint inhibitors remains unclear. We found that among body composition-related biomarkers, sarcopenia based on skeletal muscle mass was strongly associated with the treatment efficacy of immune checkpoint inhibitors in patients with metastatic renal cell carcinoma. However, body composition-related biomarkers based on subcutaneous or visceral fat were not associated with treatment efficacy. The skeletal muscle releases myokines to activate the immune system. Therapeutic interventions for sarcopenia may not only improve patients' quality of life but also improve the therapeutic effects of immune checkpoint inhibitors and prolong the prognosis of patients. Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of metastatic renal cell carcinoma (mRCC); however, validating body composition-related biomarkers for their efficacy remains incomplete. We evaluated the association between body composition-related markers and the prognosis of patients with mRCC who received ICI-based first-line therapies. Patients and Methods: We retrospectively investigated 60 patients with mRCC who underwent ICI-based therapy as their first-line treatment between 2019 and 2023. Body composition variables, including skeletal muscle, subcutaneous fat, and visceral fat indices, were calculated using baseline computed tomography scans. Sarcopenia was defined according to sex-specific cut-off values of the skeletal mass index. The associations between body composition indices and objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were evaluated. Results: Patients with sarcopenia had lower ORR and DCR than those without sarcopenia (33.3% vs. 61.1%, p = 0.0436 and 52.4% vs. 94.4%, p = 0.0024, respectively). Patients with sarcopenia had a significantly shorter median PFS (14 months vs. not reached, p = 0.0020) and OS (21 months vs. not reached, p = 0.0023) than patients without sarcopenia did. Sarcopenia was a significant predictor of PFS (hazard ratio [HR], 4.31; 95% confidence interval [CI], 1.65–14.8; p = 0.0018) and OS (HR, 5.44; 95% CI, 1.83–23.4; p = 0.0013) along with poor IMDC risk. No association was found between the subcutaneous, visceral, and total fat indices and the therapeutic effect of ICI-based therapy. Conclusions: Sarcopenia was associated with a lower response and shorter survival rates in patients with mRCC who received first-line ICI-based therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: With the development of modern systemic therapy, the role and indications of PMRT need to be further investigated in early-stage N1 breast cancer patients who have received upfront mastectomy, as recent guidelines still do not reach a consensus. Our study aimed to identify risk factors that may worsen treatment outcomes, and found that three lymph node metastases were prognostic for loco-regional control (LRC), disease-free survival (DFS), and lympho-vascular invasion (LVI) for overall survival (OS). However, the benefit of PMRT was not evident even in patients with these risk factors, and the results were similar after propensity score matching. Moreover, the incidence of arm lymphedema was significantly higher after PMRT. Therefore, we cautiously suggest omitting PMRT in T1-2N1 breast cancer patients, given the similar oncologic outcomes and increased risk of RT-related toxicity after PMRT. This study aimed to evaluate the role of post-mastectomy radiotherapy (PMRT) in T1-2N1 breast cancer. Between 2006 and 2014, a total of 504 patients with T1-2N1 breast cancer were analyzed. PMRT was administered to 71 patients, and 1:2 propensity score matching (PSM) was performed between the PMRT and non-PMRT groups. Loco-regional control (LRC), disease-free survival (DFS), and overall survival (OS) rates were compared according to PMRT status. Thirteen and one loco-regional recurrences were observed in the PMRT and non-PMRT groups, respectively. Before PSM, the 8-year LRC, DFS, and OS rates in the non-PMRT and PMRT groups were 98.5% and 96.5% (p = 0.426), 89.7% and 91.2% (p = 0.700), and 91.5% and 92.1% (p = 0.679), respectively. Corresponding rates were 95.6% and 96.5% (p = 0.365), 84.1% and 91.2% (p = 0.185), and 88.4% and 92.1% (p = 0.276), respectively, after PSM. Multivariate analysis showed that three lymph node metastases were prognostic for LRC and DFS rates and LVI for OS rate. Arm lymphedema developed in 32.4% of patients who received PMRT, which was significantly higher than the non-PMRT group (p < 0.001). Contributions of PMRT for improvement of treatments outcomes in T1-2N1 breast cancer patients were not evident, while the incidence of arm lymphedema significantly increased after PMRT. Further prospective trials are required to re-evaluate the role of PMRT. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths worldwide, but effective prognostic markers are lacking. Methionyl-tRNA synthetase 1 (MARS1), a critical enzyme in translation initiation that transfers Met to the initiator tRNA, has been implicated in cancer development and progression. MARS1 expression was significantly increased in PDAC versus normal pancreatic duct tissues. Additionally, high expression of MARS1 was associated with a poor prognosis in patients with PDAC. Our findings suggest that MARS1 is involved in pancreatic carcinogenesis and has potential as a novel prognostic marker for PDAC. The serum level of CA 19-9 is a prognostic marker for pancreatic ductal adenocarcinoma (PDAC). We evaluated the ability of the expression level of methionyl-tRNA synthetase 1 (MARS1)—which facilitates cancer growth by modulating protein synthesis and the cell cycle—to predict the prognosis of PDAC. Immunohistochemical (IHC) staining was performed on pancreatic specimens obtained from patients with PDAC who were undergoing surgery. High MARS1 expression was defined as equal to, or greater than, that in normal acinar cells. Low MARS1 expression was defined as weaker than in normal acinar cells, and stronger than in the pancreatic duct epithelium. Univariate and multivariate analyses were performed on other factors related to prognosis. Among 137 PDAC patients, no significant differences in baseline characteristics were found between those with high (n = 82) and low (n = 55) MARS1 expression. The median overall survival time of patients with high MARS1 expression was shorter than that of those with low expression (15.2 versus 17.2 months, log-rank test p = 0.044). The median disease-free survival (DFS) was not significantly different between the two groups. However, the DFS was shorter in patients with high than in those with low MARS1 expression (8.9 versus 11.2 months, log-rank test p = 0.067). In a multivariate analysis, lymph node metastasis and high MARS1 expression were associated with a poor prognosis of PDAC. Elevated MARS1 expression detected by IHC staining is associated with a poor prognosis of PDAC, suggesting that MARS1 has potential as a prognostic marker. [ABSTRACT FROM AUTHOR]

Simple Summary: One of the main challenges faced by cancer immunotherapy is the emergence of resistance against monotherapies, mediated by several immune escape mechanisms, which are able to impair therapy outcomes. Here, we investigated the biological properties of two novel bispecific constructs, known as tribodies, previously generated in our laboratory. These two bispecific molecules, named TR0304 and TR0506, are able to bind simultaneously to two immune checkpoints, i.e., LAG-3 and PD-L1 or LAG-3 and PD-1, respectively. After testing their effects on lymphocytes and on co-cultures of immune and tumor cells by comparing them to the monoclonal antibodies currently approved for clinical use, we found that these new constructs were able to activate the hPBMCs more efficiently than clinically validated mAbs, leading to stronger tumor cell lysis and, thus, showing their therapeutic potential for monotherapy-resistant tumors. Many advances in antitumor therapies have been achieved with antagonistic antibodies targeting the programmed cell death protein 1 (PD-1) or its ligand (PD-L1); however, many cancer patients still develop resistance to anti–PD-1/PD-L1 treatments often associated with the upregulation of other immune checkpoints such as Lymphocyte Activation Gene-3 (LAG-3). In order to verify whether it is possible to overcome these limits, we analyzed and compared the effects of combinations of the clinically validated anti-LAG-3 mAb (Relatlimab) with anti-PD-1 (Pembrolizumab) or anti-PD-L1 (Atezolizumab) monoclonal antibodies (mAbs) with those of novel bispecific tribodies (TRs), called TR0304 and TR0506, previously generated in our lab by combining the binding moieties of novel human antibodies targeting the same ICs of the mentioned mAbs. In particular, TR0304, made up of a Fab derived from an anti-PD-L1 mAb and two single-chain variable fragments (scFvs) derived from an anti-LAG-3 mAb, was tested in comparison with Relatlimab plus Atezolizumab, and TR0506, made up of an antigen-binding fragment (Fab) derived from the same anti-LAG-3 mAb and two scFvs derived from an anti-PD-1 mAb, was tested in comparison with Relatlimab and Pembrolizumab. We found that the two novel TRs showed similar binding affinity to the targets with respect to validated mAbs, even though they recognized distinct or only partially overlapping epitopes. When tested for their functional properties, they showed an increased ability to induce lymphocyte activation and stronger in vitro cytotoxicity against tumor cells compared to combinatorial treatments of clinically validated mAbs. Considering that tribodies also have other advantages with respect to combinatorial treatments, such as reduced production costs and lower dose requirements, we think that these novel immunomodulatory TRs could be used for therapeutic applications, particularly in monotherapy-resistant cancer patients. [ABSTRACT FROM AUTHOR]

Simple Summary: The treatment and prognosis of colorectal cancer (CRC) patients vary depending on their disease stage at diagnosis. Understanding the processes of tumorigenesis and disease development can reveal new therapeutic targets and guide patient management. On the basis of this, we investigated the molecular profiles of 237 patients with stage III CRC enrolled in the international IDEA study. We also correlated the molecular profile with Toll-like and vitamin D receptor polymorphisms, clinicopathological and epidemiological characteristics, and patient outcomes. This study suggests that the molecular characterization of tumor cells may contribute to the understanding of the biological disease course. Mutations can serve as promising prognostic biomarkers leading to better treatment options. If the results are confirmed in larger patient cohorts, then this is expected to guide clinical decision-making and personalized and improved care, and reduce treatment toxicity and patient and health system costs. Background: This study aimed to investigate the molecular profiles of 237 stage III CRC patients from the international IDEA study. It also sought to correlate these profiles with Toll-like and vitamin D receptor polymorphisms, clinicopathological and epidemiological characteristics, and patient outcomes. Methods: Whole Exome Sequencing and PCR-RFLP on surgical specimens and blood samples, respectively, were performed to identify molecular profiling and the presence of Toll-like and vitamin D polymorphisms. Bioinformatic analysis revealed mutational status. Results: Among the enrolled patients, 63.7% were male, 66.7% had left-sided tumors, and 55.7% received CAPOX as adjuvant chemotherapy. Whole exome sequencing identified 59 mutated genes in 11 different signaling pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) CRC panel. On average, patients had 8 mutated genes (range, 2–21 genes). Mutations in ARAF and MAPK10 emerged as independent prognostic factors for reduced DFS (p = 0.027 and p < 0.001, respectively), while RAC3 and RHOA genes emerged as independent prognostic factors for reduced OS (p = 0.029 and p = 0.006, respectively). Right-sided tumors were also identified as independent prognostic factors for reduced DFS (p = 0.019) and OS (p = 0.043). Additionally, patients with tumors in the transverse colon had mutations in genes related to apoptosis, PIK3-Akt, Wnt, and MAPK signaling pathways. Conclusions: Molecular characterization of tumor cells can enhance our understanding of the disease course. Mutations may serve as promising prognostic biomarkers, offering improved treatment options. Confirming these findings will require larger patient cohorts and international collaborations to establish correlations between molecular profiling, clinicopathological and epidemiological characteristics and clinical outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: We provide the first comprehensive systematic review and meta-analysis examining the impact of tumor location and treatment modalities on health-related quality of life (HRQoL) in patients with meningioma. We systematically reviewed HRQoL outcomes for non-skull base meningiomas (NSBMs), anterior, middle, and posterior fossa skull base meningiomas (SBMs) following neurosurgical and/or radiotherapeutic intervention. The literature was searched for studies that investigated HRQoL following surgical resection, radiosurgery, or radiotherapy and was analyzed to reveal HRQoL outcomes based on tumor location. With regard to therapeutic intervention, craniotomy was associated with significantly higher improvements in postoperative Karnofsky Performance Status (KPS) scores following treatment of anterior/middle skull base meningiomas (SBMs) in comparison to posterior SBMs. The authors further investigate factors that may impact HRQoL and the occurrence of postoperative neurological deficits. Due to a lack of consensus on the use of standardized quantitative tools to measure HRQoL, results are difficult to compare within the literature. We therefore provide recommendations on the utility of pertinent HRQoL instruments based upon skull base region and treatment modality. Patients with meningiomas may have reduced health-related quality of life (HRQoL) due to postoperative neurological deficits, cognitive dysfunction, and psychosocial burden. Although advances in surgery and radiotherapy have improved progression-free survival rates, there is limited evidence regarding treatment outcomes on HRQoL. This review examines HRQoL outcomes based on tumor location and treatment modality. A systematic search in PubMed yielded 28 studies with 3167 patients. The mean age was 54.27 years and most patients were female (70.8%). Approximately 78% of meningiomas were located in the skull base (10.8% anterior, 23.3% middle, and 39.7% posterior fossae). Treatment modalities included craniotomy (73.6%), radiotherapy (11.4%), and endoscopic endonasal approach (EEA) (4.0%). The Karnofsky Performance Scale (KPS) was the most commonly utilized HRQoL instrument (27%). Preoperative KPS scores > 80 were associated with increased occurrence of postoperative neurological deficits. A significant difference was found between pre- and post-operative KPS scores for anterior/middle skull base meningiomas (SBMs) in comparison to posterior (SBMs) when treated with craniotomy. Post-craniotomy SF-36 scores were lower for posterior SBMs in comparison to those in the anterior and middle fossae. Risk factors for poor neurological outcomes include a high preoperative KPS score and patients with posterior SBMs may experience a greater burden in HRQoL. [ABSTRACT FROM AUTHOR]

Simple Summary: Statistical predictive models using one of the most important strategies, known as results-based management (RBM), are relevant for improving the quality of medical services and could be used with cancer data statistics to monitor and evaluate children with cancer. We provided a comparative analysis of three predictive models that are considered robust in the literature. We also provided a tool to identify new medical cases that confirm a forecast increase or decrease in certain performance indicators and can convert data into useful information for decision-making; we propose to apply this approach to cancer data statistics at one of the National Institutes of Health in Mexico City. Our findings show that from an RBM-based perspective, predictive models are a valid and reliable instrument to forecast medical performance indicator results and can be applied to monitor and evaluate children with cancer. Predictive models play a crucial role in RBMs to analyze performance indicator results to manage unexpected events and make timely decisions to resolve them. Their use in Mexico is deficient, and monitoring and evaluation are among the weakest pillars of the model. In response to these needs, the aim of this study was to perform a comparative analysis of three predictive models to analyze 10 medical performance indicators and cancer data related to children with cancer. To accomplish these purposes, a comparative and retrospective study with nonprobabilistic convenience sampling was conducted. The predictive models were exponential smoothing, autoregressive integrated moving average, and linear regression. The lowest mean absolute error was used to identify the best model. Linear regression performed best regarding nine of the ten indicators, with seven showing p < 0.05. Three of their assumptions were checked using the Shapiro–Wilk, Cook's distance, and Breusch–Pagan tests. Predictive models with RBM are a valid and relevant instrument for monitoring and evaluating performance indicator results to support forecasting and decision-making based on evidence and must be promoted for use with cancer data statistics. The place numbers obtained by cancer disease inside the main causes of death, morbidity and hospital outpatients in a National Institute of Health were presented as evidence of the importance of implementing performance indicators associated with children with cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Due to the lack of progress in OsA's treatment and survival, there is a need to develop new therapeutic approaches for this tumor. OsA is a complex tumor for which the immune microenvironment appears as a potential therapeutic option. This study explores the antitumor effect of a chemically detoxified TLR4 agonist MP-LPS, under liposomal formulation called Lipo-MP-LPS. The agent induces a significant antitumor response and inhibition of tumor growth in an immunocompetent OsA model. Lipo-MP-LPS acts by favoring the switch of M2 macrophages to M1, and promotes T-cell recruitment. The study suggests that Lipo-MP-LPS could be used alone or in combination with other therapies for refractory tumors like OsA. Osteosarcoma (OsA) has limited treatment options and stagnant 5-year survival rates. Its immune microenvironment is characterized by a predominance of tumor-associated macrophages (TAMs), whose role in OsA progression remain unclear. Nevertheless, immunotherapies aiming to modulate macrophages activation and polarization could be of interest for OsA treatment. In this study, the antitumor effect of a liposome-encapsulated chemically detoxified lipopolysaccharide (Lipo-MP-LPS) was evaluated as a therapeutic approach for OsA. Lipo-MP-LPS is a toll-like receptor 4 (TLR4) agonist sufficiently safe and soluble to be IV administered at effective doses. Lipo-MP-LPS exhibited a significant antitumor response, with tumor regression in 50% of treated animals and delayed tumor progression in the remaining 50%. The agent inhibited tumor growth by 75%, surpassing the efficacy of other immunotherapies tested in OsA. Lipo-MP-LPS modulated OsA's immune microenvironment by favoring the transition of M2 macrophages to M1 phenotype, creating a proinflammatory milieu and facilitating T-cell recruitment and antitumor immune response. Overall, the study demonstrates the potent antitumor effect of Lipo-MP-LPS as monotherapy in an OsA immunocompetent model. Reprogramming macrophages and altering the immune microenvironment likely contribute to the observed tumor control. These findings support the concept of immunomodulatory approaches for the treatment of highly resistant tumors like OsA. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic adenocarcinoma is the fourth leading cause of cancer-related death in industrialized countries. In locally advanced and borderline resectable pancreatic cancer, neoadjuvant therapy (NAT) has been shown to be effective in eliminating potentially circulating tumor cells and distant micrometastases, shrinking local tumors, and identifying high-grade malignancies that do not benefit from surgery. However, in patients with resectable pancreatic adenocarcinoma, who represent 20% of new diagnoses and for whom US followed by adjuvant chemotherapy is the standard of care, NAT is controversial because it carries several potential drawbacks that may prevent surgery and increase the risk of clinical deterioration. Randomized clinical trials, retrospective studies, and a few systematic reviews and meta-analyses reported controversial results, and although the safety and feasibility of such an approach are supported, a wider implementation is still a matter of debate. Considering the different methodological approaches (RCTs vs. retrospective studies), the difficulty in providing high-quality evidence due to small patient numbers, and the emergence of new evidence, an update of the current evidence seems essential to help clinicians and researchers understand the role of NAT and offer a new potentially beneficial treatment approach. Thus, the aim of this systematic review and meta-analysis is to evaluate the role of NAT in prolonging overall survival and disease-free survival and improving R0 and N0 rates compared with upfront resection in patients with resectable pancreatic cancer. Background: Despite advances in treatment, the prognosis of resectable pancreatic adenocarcinoma remains poor. Neoadjuvant therapy (NAT) has gained great interest in hopes of improving survival. However, the results of available studies based on different treatment approaches, such as chemotherapy and chemoradiotherapy, showed contrasting results. The aim of this systematic review and meta-analysis is to clarify the benefit of NAT compared to upfront surgery (US) in primarily resectable pancreatic adenocarcinoma. Methods: A PRISMA literature review identified 139 studies, of which 15 were finally included in the systematic review and meta-analysis. All data from eligible articles was summarized in a systematic summary and then used for the meta-analysis. Specifically, we used HR for OS and DFS and risk estimates (odds ratios) for the R0 resection rate and the N+ rate. The risk of bias was correctly assessed according to the nature of the studies included. Results: From the pooled HRs, OS for NAT patients was better, with an HR for death of 0.80 (95% CI: 0.72–0.90) at a significance level of less than 1%. In the sub-group analysis, no difference was found between patients treated with chemoradiotherapy or chemotherapy exclusively. The meta-analysis of seven studies that reported DFS for NAT resulted in a pooled HR for progression of 0.66 (95% CI: 0.56–0.79) with a significance level of less than 1%. A significantly lower risk of positive lymph nodes (OR: 0.45; 95% CI: 0.32–0.63) and an improved R0 resection rate (OR: 1.70; 95% CI: 1.23–2.36) were also found in patients treated with NAT, despite high heterogeneity. Conclusions: NAT is associated with improved survival for patients with resectable pancreatic adenocarcinoma; however, the optimal treatment strategy has yet to be defined, and further studies are required. [ABSTRACT FROM AUTHOR]

Simple Summary: Complementary therapies, such as acupuncture, yoga and herbal medicine are used by many patients with cancer to relieve symptoms and side effects from anti-cancer treatment. Clinicians in oncology often lack the knowledge to adequately advise patients about the potential benefits and risks of complementary therapies. This study aims to provide an overview of recently published systematic reviews of the effects of complementary therapies on patient-reported health outcomes in patients with cancer. One hundred systematic reviews were included, and the results suggest that several complementary therapies can improve patient-reported health outcomes in patients with cancer. For instance, acupuncture to relieve pain and yoga to improve cancer-related fatigue. The results remain inconclusive for other complementary therapies. Many included systematic reviews did not assess the impact of bias on their results. Nonetheless, the results from this study can help clinicians to find information about the evidence base for complementary therapies when counselling patients on this topic. Many patients with cancer make use of complementary medicine alongside conventional medicine, but clinicians in oncology often lack the knowledge to adequately advise patients on the evidence base for complementary therapies. This study aims to provide an overview of recently published systematic reviews that assess the effects of complementary therapies on patient-reported health outcomes in patients with cancer. Systematic reviews, including a meta-analysis of at least two randomized controlled trials, were identified from the PubMed, Embase, Cochrane Library, CINAHL and PsycINFO databases. The methodological quality was assessed with AMSTAR 2. One hundred systematic reviews were included. The results suggest that several complementary therapies can improve health outcomes reported by patients with cancer, such as acupuncture to relieve pain, music interventions to reduce anxiety and yoga to improve cancer-related fatigue. The side effects related to complementary therapy use are generally mild. The results remain inconclusive for some intervention–outcome combinations. Many of the included systematic reviews insufficiently assessed the causes and impact of bias in their interpretation of the results. This overview of systematic reviews can support clinicians in counselling their patients on this topic and provide directions for future research and clinical practice guidelines in the field of complementary medicine. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune checkpoint inhibitors (ICIs) have transformed the treatment paradigm for metastatic non-small cell lung cancer (NSCLC) patients (IB-IIIA) with no targetable driver mutations. Although genetic and physiological factors could suggest a priori differences in response to ICIs regarding sex, there are few works addressing it, and the available results are confusing. It is well established that women have a more proficient immune system; thus, a higher immune editing level is needed to develop metastatic disease, which could explain their better responses in the early phases of disease. Furthermore, the encouraging results observed for metastatic disease have promoted the use of ICIs as neoadjuvant treatments. Here, we aimed to first review the landscape of current neoadjuvant settings used in resectable NSCLC patients, before analyzing whether sex may be a factor that modulates responses to ICIs. To this end, we have carried out a meta-analysis of the available data. Non-small cell lung cancer (NSCLC) is one of the world's leading causes of morbidity and mortality. ICIs alone or combined with chemotherapy have become the standard first-line treatment of metastatic NSCLC. The impressive results obtained have stimulated our interest in applying these therapies in early disease stage treatments, as neoadjuvant immunotherapy has shown promising results. Among many of the factors that may influence responses, the role played by sex is attracting increased interest and needs to be addressed. Here, we aim to first review the state of the art regarding neoadjuvant ICIs, whether they are administered in monotherapy or in combination with chemotherapy at stages IB-IIIA, particularly at stage IIIA, before analyzing whether sex may influence responses. To this end, a meta-analysis of publicly available data comparing male and female major pathological responses (MPR) and pathological complete responses (pCR) was performed. In our meta-analysis, MPR was found to be significantly higher in females than in males, with an odds ratio (OR) of 1.82 (95% CI 1.13–2.93; p = 0.01), while pCR showed a trend to be more favorable in females than in males, but the OR of 1.62 was not statistically significant (95% CI 0.97–2.75; p = 0.08). Overall, our results showed that sex should be systematically considered in future clinical trials settings in order to establish the optimal treatment sequence. [ABSTRACT FROM AUTHOR]

Simple Summary: Based on previous work, we designed a new questionnaire that asks patients to report how they feel after undergoing plaque radiation treatment for a certain type of eye cancer. This study aimed to test that the questionnaire measured what it was intended to measure. The questionnaire was given to 439 patients from three clinics in Canada and the United States of America. The results indicated that the questionnaire measures three domains: symptoms and their impact on the patient, the patient's worry, and the patient's discomfort. The questionnaire is easy to use and reliable. The questionnaire can help doctors manage patient care after the treatment. The objective of this study was to evaluate the psychometric properties of a new patient-reported outcome instrument intended for use with patients who have undergone brachytherapy for uveal melanoma (PROM-UM). Classical test theory and item response theory were used to evaluate the performance of individual items and domains. A convenience sample of 439 participants who had undergone brachytherapy for uveal melanoma from one of three North American ocular oncology treatment centers were included in this cross-sectional study. Exploratory factor analysis identified three domains which were labelled "Symptom Impairment", "Worry", and "Discomfort". The acceptability of the instrument was supported by little missing data (range = 0.00–1.14%) and low maximum endorsement (range = 0.00–1.82%). Item-total (range = 0.68–0.85) and inter-item (range = 0.74–0.80) correlations indicated acceptable reliability. Discrimination and difficulty were assessed using item response theory. Items in all three domains indicated moderate to very high discrimination (range = 1.00–4.10). Two items in the Symptom Impairment domain were too difficult to measure. Response ranges in the other two domains demonstrated acceptable difficulty. These results from the study indicate that this new patient-reported outcome instrument can be used with patients treated with brachytherapy for uveal melanoma. Providers could use this instrument to help inform post-treatment management. [ABSTRACT FROM AUTHOR]