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BackgroundStandard treatment for patients with newly diagnosed glioblastoma includes surgery, radiotherapy (RT), and temozolomide (TMZ) chemotherapy (TMZ/RT→TMZ). The proteasome has long been considered a promising therapeutic target because of its role as a central biological hub in tumor cells. Marizomib is a novel pan-proteasome inhibitor that crosses the blood-brain barrier.MethodsEuropean Organisation for Research and Treatment of Cancer 1709/Canadian Cancer Trials Group CE.8 was a multicenter, randomized, controlled, open-label phase 3 superiority trial. Key eligibility criteria included newly diagnosed glioblastoma, age > 18 years and Karnofsky performance status > 70. Patients were randomized in a 1:1 ratio. The primary objective was to compare overall survival (OS) in patients receiving marizomib in addition to TMZ/RT→TMZ with patients receiving the only standard treatment in the whole population and in the subgroup of patients with MGMT promoter-unmethylated tumors.ResultsThe trial was opened at 82 institutions in Europe, Canada, and the U.S. A total of 749 patients (99.9% of the planned 750) were randomized. OS was not different between the standard and the marizomib arm (median 17 vs. 16.5 months; HR = 1.04; P = .64). PFS was not statistically different either (median 6.0 vs. 6.3 months; HR = 0.97; P = .67). In patients with MGMT promoter-unmethylated tumors, OS was also not different between standard therapy and marizomib (median 14.5 vs. 15.1 months, HR = 1.13; P = .27). More CTCAE grade 3/4 treatment-emergent adverse events were observed in the marizomib arm than in the standard arm.ConclusionsAdding marizomib to standard temozolomide-based radiochemotherapy resulted in more toxicity, but did not improve OS or PFS in patients with newly diagnosed glioblastoma.

Radiation treatment plays a mainstream role in the management of head and necksquamous cell carcinomas (HNSCCs). Adverse effects from radiation therapy include osteoradionecrosis of the jaw, and rarely, pathologic fracture. Immune checkpoint inhibitors (ICI) such as pembrolizumab are of growing relevance to the management of metastatic and recurrent HNSCCs. Adverse impacts on bone secondary to medications such as pembrolizumab and nivolumab have been sporadically documented in the literature. The objective of this manuscript is to raise awareness of possible increase in risk for adverse jaw outcomes in patients with HNSCCs exposed to both radiation treatment to the jaws and ICI therapy. This manuscript documents adverse jaw outcomes including osteonecrosis and pathologic fracture of the mandible in two patients receiving pembrolizumab for management of HNSCC who had received prior radiation treatment. A potential link between immunotherapy and adverse jaw outcomes is consistent with the growing understanding of osteoimmunology, investigating the closely interrelated processes in bone remodeling and immune system function, in health and disease. It is important to ascertain if pembrolizumab poses an incremental risk for such outcomes, beyond the risk from prior radiation, for patients managed with radiation treatment and ICI therapy for HNSCC. The general dental practitioner may encoun-tersuch patients either in the context of facilitating dental clearance prior to initiation of chemotherapy, or rarely, with poorly explained jaw symptoms and must be alert to the possibility of occurrence of such adverse jaw events to facilitate timely diagnosis and optimal patient management. [ABSTRACT FROM AUTHOR]

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.To assess long-term risk of local tumor regrowth, we report updated organ preservation rate and oncologic outcomes of the OPRA trial (ClinicalTrials.gov identifier: NCT02008656). Patients with stage II/III rectal cancer were randomly assigned to receive induction chemotherapy followed by chemoradiation (INCT-CRT) or chemoradiation followed by consolidation chemotherapy (CRT-CNCT). Patients who achieved a complete or near-complete response after finishing treatment were offered watch-and-wait (WW). Total mesorectal excision (TME) was recommended for those who achieved an incomplete response. The primary end point was disease-free survival (DFS). The secondary end point was TME-free survival. In total, 324 patients were randomly assigned (INCT-CRT, n = 158; CRT-CNCT, n = 166). Median follow-up was 5.1 years. The 5-year DFS rates were 71% (95% CI, 64 to 79) and 69% (95% CI, 62 to 77) for INCT-CRT and CRT-CNCT, respectively (P = .68). TME-free survival was 39% (95% CI, 32 to 48) in the INCT-CRT group and 54% (95% CI, 46 to 62) in the CRT-CNCT group (P = .012). Of 81 patients with regrowth, 94% occurred within 2 years and 99% occurred within 3 years. DFS was similar for patients who underwent TME after restaging (64% [95% CI, 53 to 78]) and patients in WW who underwent TME after regrowth (64% [95% CI, 53 to 78]; P = .94). Updated analysis continues to show long-term organ preservation in half of the patients with rectal cancer treated with total neoadjuvant therapy. In patients who enter WW, most cases of tumor regrowth occur in the first 2 years.

Background: The evidence for adjuvant chemoradiotherapy (CRT) of oral cavity squamous cell carcinoma (OCSCC) with extra-nodal extension (ENE) in National Comprehensive Cancer Network (NCCN) guidelines is derived from patients with head and neck cancer. The guidelines further suggest a radiation dose ranging from 6000 to 6600 cGy. In this nationwide study, we sought to evaluate the prognostic significance of adjuvant therapy and the specific radiation dosage in Taiwanese patients with pure OCSCC and ENE. Methods: A retrospective analysis of 1577 OCSCC patients with ENE who underwent resection and received adjuvant CRT or radiotherapy (RT) between January 2011 and December 2020 was conducted. Results: Multivariable analysis revealed that adjuvant RT, more than four pathologically positive nodes, and radiation dosage below 6000 cGy were independent risk factors for unfavorable 5-year disease-specific survival (DSS) and overall survival (OS). Comparing patients who received CRT (n = 1453) to those treated with RT (n = 124) before and after propensity score (PS) matching, the 5-year outcomes were as follows: before PS matching, DSS (54% versus 30%, p < 0.0001), OS (42% versus 18%, p < 0.0001); after PS matching (n = 111 in each group), DSS (52% versus 30%, p = 0.0016), OS (38% versus 21%, p = 0.0019). For patients who underwent CRT, the 5-year outcomes for different radiation dose groups (6600 − 7000 cGy, n = 1155 versus 6000 − 6500 cGy, n = 199) were as follows: before PS matching, DSS (52% versus 54%, p = 0.1904), OS (43% versus 46%, p = 0.1610); after PS matching (n = 199 in each group), DSS (55% versus 54%, p = 0.8374), OS (46.5% versus 46.3%, p = 0.7578). Conclusions: For OCSCC patients with ENE, our study shows CRT improved survivals than RT alone, underscoring the clinical significance of chemotherapy. Patients undergoing CRT with irradiation doses ranging from 6000 to 6500 cGy exhibited comparable survival outcomes to those receiving doses of 6600–7000 cGy. This observation suggests that irradiation doses exceeding the 6600 cGy may not confer the survival advantage in these patients. Further research is needed to confirm our results and explore the optimal irradiation dose for managing these patients. [ABSTRACT FROM AUTHOR]

Patients with supraclavicular lymph node (SLN) metastasis from esophageal cancer encounter significant variations in treatment approaches due to differences in pathological subtypes and the lack of a unified regional staging system between East Asian and Western countries. The Tiger study aims to develop an internationally recognized staging system and to delineate the extent of regional lymph node dissection. In the context of esophageal squamous cell carcinoma (SCC) with SLN metastasis, the treatment paradigms from East Asia offer valuable insights. The Japan Esophageal Society (JES) 12th edition staging system guides a tailored comprehensive treatment strategy, emphasizing either radiotherapy and chemotherapy or surgical intervention. In contrast, esophageal adenocarcinoma (AC) predominates in Western countries, where the 8th edition of the American Joint Committee on Cancer (AJCC) staging system classifies SLN metastasis as a distant metastasis, advocating for systemic therapy as the primary treatment modality. Nonetheless, compelling evidence suggests that a multidisciplinary treatment approach, incorporating either radiotherapy and chemotherapy or surgery as the initial treatment, can yield superior outcomes for these patients compared to chemotherapy alone. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate clinical outcomes and prognostic factors in non-metastatic oral cavity squamous cell carcinoma (OCSCC) patients who underwent surgery with or without adjuvant therapy. Methods: From 2007 and 2018, 116 patients were analyzed. The primary endpoint was overall survival (OS), and secondary endpoints were disease-free survival (DFS), local failure (LF), regional failure (RF), and distant metastases (DM). Kaplan-Meier method and log-rank test assessed survival outcomes, while Cox proportional hazard tests analyzed prognostic factors. Results: Median patient age was 53 years, most were smokers (93.5%) and males (62.9%). Predominant subsite was the oral tongue (58.6%). Treatment included surgery alone (16.4%), adjuvant radiotherapy (46.6%), or adjuvant concurrent chemoradiotherapy (CCRT) (37%). The median follow-up time was 45.9 months. There were significant differences between groups in terms of gender (P=0.028) and RT dose (P=0.01). The 3-year OS, DFS, LF, RF and DM for the entire cohort were 60.9%, 55.1%, 20.11%, 8.43%, and 17.13%, respectively. Surgery alone yielded higher 3-year OS (81.4%) than adjuvant RT (70%) or adjuvant CCRT (41.4%), (p=0.012). Adjuvant CCRT correlated with higher LF compared to adjuvant RT and surgery alone groups (p=0.029). Lymphovascular invasion (LVI) impacted OS (HR=2.034, p=0.0498) and DM (HR=3.380, p=0.0132), while higher tumor grade increased DM likelihood (HR=8.477, p=0.0379). Conclusions: This study reports OCSCC patient outcomes in Jordan across different treatment modalities. Adjuvant CCRT correlated with higher LF rates, and LVI impacted OS and DM, aligning with existing OCSCC treatment literature. [ABSTRACT FROM AUTHOR]

Total neoadjuvant therapy (TNT) of rectal cancer improves rates of pathological complete remission and progression-free survival. With improved clinical response rates, interest grew in a non-operative approach/watch and wait (WaW) for this disease. In 2020, the working groups of ACO/AIO/ARO published a consensus statement on the use of TNT, including a non-operative approach. However, the best combination scheme remains unclear. Despite the increasing use of TNT, there is a lack of comprehensive data on its current implementation and practices. To address this knowledge gap, a multicenter survey was conducted to capture the use of TNT protocols in German-speaking radiotherapy departments. At the beginning of 2023, a GDPR-compliant online survey was conducted in Germany, Austria, and German-speaking Switzerland. The questionnaire comprised 43 questions covering various aspects of TNT, including chemotherapy and WaW concepts. Most respondents (98.4%) confirmed awareness of the consensus on TNT for rectal cancer. Institutions treated an average of 30.22 rectal cancer patients annually. Most respondents (76.2%) reported treating over 80% of patients neoadjuvantly. Regarding TNT, 33.3% treated 21–50% with such a protocol. No significant association was found between the institution type and TNT application. In 62/63 cases, tumor board discussion was standard before offering TNT. VMAT was the predominant technique (82.5%). For rectal cancer dosing, the 50/50.4Gy scheme was most common, followed by 45Gy with a boost and the 5 × 5Gy scheme. Dosing schemes for TNT varied slightly, with more participants reporting the use of 5 × 5Gy compared to radiation therapy for rectal cancer in general. CBCT was the primary IGRT method (88.9%). Larger hospitals typically administered chemotherapy themselves, while private practices collaborated with medical oncologists (p < 0.0001). The most common concurrent chemotherapy drugs were 5-fluorouracil/capecitabine (64.4%) and oxaliplatin (37.3%). A WaW strategy was reported to be institutional implemented by 63.8%. The timing of offering WaW was split, with 50% offering it after radiochemotherapy and 47% during the informed consent talk. For planned WaW, 62% prefer normofractionated TNT. TNT appears to be widely implemented in the German-speaking radio-oncological community, regardless of the type of institution. Image-guided therapy, multidisciplinary team decisions, and internal guidelines play an important role. TNT seems to have already altered treatment protocols for rectal cancer toward an organ-preserving approach in selected cases. In these WaW cases, normofractionation appears to be preferred over hypofractionation. [ABSTRACT FROM AUTHOR]

Background: Dose escalation with brachytherapy after pelvic irradiation is standard for treating cervical cancer. Its application can be impossible for some patients. Dose escalation with SBRT is widely used with high local control and acceptable toxicity rates in different body parts. The study enrolled patients who underwent SBRT treatment for dose escalation in the cervix. Methods: Patients who were pathologically diagnosed and treated with cervical SBRT after definitive CRT were included in the study. A total of 30 Gy in 5 fractions for the high-risk volume was prescribed. The first response evaluation was performed three months after the completion of treatment. Treatment toxicity was documented according to the RTOG-EORTC scale. Oncological outcomes and toxicity were assessed. Results: Between 02.2019 and 05.2023, 40 patients were treated with an SBRT boost after pelvic irradiation. The median follow-up time was 16 months (7–44 months). The median HR CTV was 47 cc (8,3-168,2 cc). There were 39 patients who achieved a complete response and one who achieved a partial response in the third month after treatment. There were two local or two regional recurrences. The 1-year metastasis-free survival was 88%, and the 1-year progression-free survival was 88%. During the follow-up period, one grade 3 gastrointestinal side effect was observed. Conclusions: SBRT which has low toxicity and reasonable locoregional control rates in a short follow-up period, may be an option for dose escalation in brachytherapy-ineligible cervical cancer patients. [ABSTRACT FROM AUTHOR]

Osteosarcoma is a highly aggressive bone cancer primarily affecting children, adolescents, and young adults. The current gold standard for treatment of osteosarcoma patients consists of two to three rounds of chemotherapy, followed by extensive surgical intervention from total limb reconstruction to amputation, followed by additional rounds of chemotherapy. Although chemotherapy has advanced the treatment of osteosarcoma significantly, the overall 5-year survival rate in resistant forms of osteosarcoma is still below 20%. The interaction between cancer and the immune system has long been recognized as a critical aspect of tumour growth. Tumour cells within the tumour microenvironment (TME) suppress antitumour immunity, and immunosuppressive cells and cytokines provide the extrinsic factors of tumour drug resistance. Emerging research demonstrates an immunostimulatory role for the cGAS/STING pathway in osteosarcoma, typically considered an immunecold or immunosuppressed cancer type. cGAS/STING signalling appears to drive an innate immune response against tumours and potentiates the efficacy of other common therapies including chemo and radiotherapy. Nanotechnological delivery systems for improved therapy delivery for osteosarcoma have also been under investigation in recent years. This review provides an overview of cGAS/STING signalling, its divergent roles in the context of cancer, and collates current research which activates cGAS/STING as an adjuvant immunomodulatory target for the treatment of osteosarcoma. It will also discuss current nanotechnological delivery approaches that have been developed to stimulate cGAS/STING. Finally, it will highlight the future directions that we believe will be central to the development of this transformative field. [ABSTRACT FROM AUTHOR]

Epithelioid glioblastoma (Ep-GBM) is a rare variant of glioblastoma characterized by a high recurrence rate and poor prognosis. Currently, there is no established standard treatment for Ep-GBM. Therefore, we identified 58 Ep-GBM cases to investigate these characteristics and identify the possible prognostic factors of survival. There were 30 male and 28 female patients with a median age of 39 years. Headaches and dizziness were the most common clinical symptom. The tumor is most frequently located in the temporal lobe (36.2%). The positivity rate for BRAF-V600E is 56.9% (33/58), for MGMT is 56.9% (33/58), and for INI-1 is 75% (30/40). Tumor recurrence was observed in 39 patients. The median progression-free survival (PFS) of all patients was 12.7 months, while the median overall survival (OS) was 29.1 months. Additionally, the median survival time after recurrence was 14.3 months. Both univariate and multivariate COX regression analyses revealed that individuals who received more than six cycles of adjuvant oral temozolomide experienced a longer median PFS compared to those who received fewer cycles. Characteristics associated with poorer PFS included tumor dissemination prior to initial surgery. Additionally, both analyses identified tumor dissemination, radiotherapy and adjuvant oral temozolomide as predictors of OS. Notably, for patients with recurrent Ep-GBM, reoperation was shown to significantly increase survival time after recurrence. In conclusion, the standard Stupp regimen is also applicable to patients with Ep-GBM, extending adjuvant oral temozolomide could further improve survival for Ep-GBM patients, reoperation may also prolong survival for recurrent Ep-GBM. [ABSTRACT FROM AUTHOR]

Purpose: To determine the utility of the novel CARWL score, which integrates C-reactive protein-to-albumin ratio (CAR) and significant weight loss (SWL), in stratifying the locally advanced nasopharyngeal carcinoma (LA-NPC) patients into significantly different radiation-induced trismus (RIT) risk groups following definitive C-CRT. Patients and methods: This retrospective study analyzed the medical records of 286 LA-NPC patients who received C-CRT between January 2010 and December 2022. The maximum mouth opening (MMO) was measured before the C-CRT, at 1, 3, 6, 9, and 12 months, and every 6 months after that during the follow-up. Additionally, the CAR value just before the commencement of C-CRT and SWL defined as a weight loss > 5% in the preceding six months were documented for each patient. RIT was defined as a MMO ≤ 35 mm. Results: The optimal CAR cut-off was 3.03 (area under the curve: 87.3%; sensitivity: 82.6%; specificity: 80.9%, J-index: 0.635), using receiver operating characteristic (ROC) curve analysis, with RIT incidence being the event. We stratified the patients into three CARWL score groups. CARWL-0: CAR < 3.0 and WL ≤ 5.0% (N = 92), CARWL-1: CAR < 3.0 and WL > 5.0% or CAR ≥ 3.0 (N = 99), and WL ≤ 5.0% and CARWL-2: CAR > 3.0 and WL > 5.0% (N = 95). The incidence of RIT increased significantly across CARWL score groups (8.7% for CARWL-0, 23.2% for CARWL-1, and 44.2% for CARWL-2; P < 0.001). Conclusion: The current study indicated that the novel CARWL scoring system is efficient in precisely stratifying LA-NPC patients into distinct RIT risk groups after C-CRT. [ABSTRACT FROM AUTHOR]

The article from the Journal of Medical Imaging & Radiation Oncology discusses the use of low-dose VMAT radiotherapy for treating actinic keratosis, a condition that can affect large areas of the skin. The study conducted at Sir Charles Gairdner Hospital in Perth, Australia, analyzed patients treated for actinic keratosis and found that VMAT radiotherapy resulted in a complete response in 100% of treated areas, with favorable patient-reported outcomes. The study demonstrated excellent short-term response with lower doses than previously published data, highlighting the potential of this treatment for actinic keratosis. [Extracted from the article]

Simple Summary: The mainstay treatment of non-metastatic muscle-invasive bladder cancer is radical cystectomy, but in patients who prefer to save their bladder and patients who are at high risk for surgery, bladder-preserving therapies, including tumor removal through complete transurethral resection and chemoradiation (TMT), provide an alternative. However, complete TURBT has significant risks of bleeding, infection, bladder perforation, and tumor cell dissemination, and its necessity in all cases remains unclear. Based on available data, the role of complete TURBT in managing MIBC as a part of a bladder-preserving approach is unclear, and individualized treatment plans and further research are needed to optimize patient outcomes. Radical cystectomy with lymph node dissection and urinary diversion is the gold-standard treatment for non-metastatic muscle-invasive bladder cancer (MIBC). However, in patients who refuse cystectomy, or in whom cystectomy carries a high risk, bladder-preserving therapies remain potential options. Bladder preservation therapies can include maximal debulking transurethral resection of bladder tumor (TURBT), concurrent chemoradiation therapy, followed by cystoscopy to assess response. At this time, maximal TURBT is recommended for patients prior to the initiation of chemoradiation therapy or in patients with residual bladder tumors after the completion of chemoradiation therapy. That being said, TURBT carries significant risks such as bladder perforation, bleeding, and infection, ultimately risking delayed systemic treatment. Hence, understanding its role within trimodal therapy is crucial to avoid undue suffering in patients. Herein, we review the current literature on the impact of debulking TURBT in non-metastatic MIBC. [ABSTRACT FROM AUTHOR]

Simple Summary: The study evaluated the long-term outcomes of chemoradiotherapy (CRT) with S-1 after limited surgery for T1 or T2 lower rectal cancer. The 3-year and 5-year relapse-free survival rates were 90.17% and 85.87%, respectively, showing favorable outcomes for T1 cancer patients, with effective anal function preservation. However, further treatment is needed to improve outcomes for T2 cancer patients. Background: The short-term outcomes of chemoradiotherapy (CRT) with S-1 (a combination of tegafur, gimeracil, and oteracil) following limited surgery for patients with T1 or T2 lower rectal cancer have shown encouraging results. Objectives: This study was designed to delve deeper into the long-term outcomes of CRT with S-1 after limited surgery, with the goal of evaluating both the long-term efficacy and potential risks associated with this treatment approach in patients diagnosed with T1 or T2 lower rectal cancer. Methods: This was conducted as a multicenter, single-arm, prospective phase II trial. The patient population consisted of individuals clinically diagnosed with either T1 or T2 lower rectal or anal canal cancer, with a maximum tumor diameter of 30 mm and classified as N0 or M0. Patients underwent local excision or endoscopic resection. After surgery, CRT with S-1 was administered to patients meeting several criteria, including the confirmation of well-differentiated or moderately differentiated adenocarcinoma, negative surgical margins, submucosal invasion depth of ≥1000 µm, and high tumor-budding grade (2/3). The primary endpoint of this study was relapse-free survival, while secondary endpoints included local recurrence-free survival, overall survival, anal sphincter preservation rate, and safety. Results: A total of 52 patients were included, with pathological diagnoses revealing T1 in 36 patients and T2 in 16 patients. The 3-year and 5-year relapse-free survival rates were 90.17% and 85.87%, respectively. The 3-year and 5-year local recurrence-free survival rates were 90.17% and 88.07%, respectively, while the 3-year and 5-year overall survival rates were 94.03% and 91.94%, respectively. Conclusions: CRT with S-1 after limited surgery for T1 lower rectal cancer demonstrated favorable outcomes in terms of recurrence, survival, and local control rates while effectively maintaining anal function in patients. However, further treatment approaches may be necessary to improve outcomes for patients diagnosed with stage T2 lower rectal cancer [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to identify prognostic factors by combining clinicopathologic parameters with tumor microenvironment (TME) biomarkers in patients with locally advanced rectal cancer (LARC) who underwent surgery following neoadjuvant chemoradiotherapy (nCRT). We analyzed CD8+ T cells, CXCR3, CXCL10, and α-SMA using immunohistochemical staining and incorporated AI-powered digital pathology to assess the spatial TME. Our findings showed that high expression of CD8+ T cells, CXCR3 in tumor-infiltrating lymphocytes (TILs), and an inflamed phenotype were associated with better recurrence-free survival (RFS). However, these factors were not predictive of overall survival (OS). Patients with an immune-desert phenotype had a poor prognosis regardless of pathologic stage or the administration of postoperative chemotherapy. These results suggest that CD8+ T cells and AI-powered immune phenotypes, together with clinical factors, can guide personalized treatment strategies in LARC patients post-nCRT and highlight the potential benefits of modifying the tumor immune microenvironment (TiME) to reduce recurrence after surgery. Background/Objectives: The tumor microenvironment (TME) has emerged as a significant prognostic factor. This study aimed to identify prognostic factors by combining clinicopathologic parameters and the TME biomarkers in patients who underwent surgery following neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer (LARC). Methods: CD8+ T cells, CXCR3, CXCL10, and α-smooth muscle actin (α-SMA) were analyzed via immunohistochemical staining. We also incorporated AI-powered digital pathology to assess the spatial TME. The associations between these biomarkers, clinicopathologic parameters, and survival outcomes were evaluated. Results: CD8+ T cell expression, CXCR3 expression in tumor-infiltrating lymphocytes (TILs), and immune phenotypes were correlated. LARC patients with a high expression of CD8+ T cells, CXCR3 in TILs, and an inflamed phenotype had a significantly better prognosis than their counterparts did. In the multivariate analysis, the expression of CD8+ T cells and the inflamed/immune-excluded phenotype were significant tumor immune microenvironment (TiME) biomarkers for recurrence-free survival (RFS) but not for overall survival (OS). Notably, patients with the immune-desert phenotype had a poor prognosis regardless of pathologic stage, even if postoperative chemotherapy was administered (p < 0.001). Conclusions: CD8+ T cells and AI-powered immune phenotypes, alongside clinical factors, can guide personalized treatment in LARC patients receiving nCRT. A therapeutic strategy to modify the TiME after nCRT could help reduce recurrence after surgery. [ABSTRACT FROM AUTHOR]

Simple Summary: Elevated levels of the mitotic checkpoint kinase BUB1 are frequently observed in most solid cancers, including lung cancer. High BUB1 expression is linked to poorer patient survival. In the present study, we aimed to evaluate if a BUB1 targeting agent could enhance the effectiveness of chemotherapy and chemoradiation in lung cancer. Our findings suggest that BUB1 inhibitor sensitizes lung cancer cell lines to chemotherapy, radiotherapy, and chemoradiation and thus validate BUB1 as a novel molecular target. Background: Despite advances in targeted therapies and immunotherapies, traditional treatments like microtubule stabilizers (paclitaxel, docetaxel), DNA-intercalating platinum drugs (cisplatin), and radiation therapy remain essential for managing locally advanced and metastatic lung cancer. Identifying novel molecular targets could enhance the efficacy of these treatments. Hypothesis: We hypothesize that BUB1 (Ser/Thr kinase) is overexpressed in lung cancers and its inhibition will sensitize lung cancers to chemoradiation. Methods: BUB1 inhibitor (BAY1816032) was combined with cisplatin, paclitaxel, a PARP inhibitor olaparib, and radiation in cell proliferation and radiation-sensitization assays. Biochemical and molecular assays evaluated the impact on DNA damage signaling and cell death. Results: Immunostaining of lung tumor microarrays (TMAs) confirmed higher BUB1 expression in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) compared to normal tissues. In NSCLC, BUB1 overexpression correlated directly with the expression of TP53 mutations and poorer overall survival in NSCLC and SCLC patients. BAY1816032 synergistically sensitized lung cancer cell lines to paclitaxel and olaparib and enhanced cell killing by radiation in both NSCLC and SCLC. Molecular analysis indicated a shift towards pro-apoptotic and anti-proliferative states, evidenced by altered BAX, BCL2, PCNA, and Caspases-9 and -3 expressions. Conclusions: Elevated BUB1 expression is associated with poorer survival in lung cancer. Inhibiting BUB1 sensitizes NSCLC and SCLC to chemotherapies (cisplatin, paclitaxel), targeted therapy (olaparib), and radiation. Furthermore, we present the novel finding that BUB1 inhibition sensitized both NSCLC and SCLC to radiotherapy and chemoradiation. Our results demonstrate BUB1 inhibition as a promising strategy to sensitize lung cancers to radiation and chemoradiation therapies. [ABSTRACT FROM AUTHOR]

Simple Summary: As the population ages, the prevalence of frailty syndrome increases, particularly among elderly patients with rectal cancer. Frail patients are more vulnerable to stressors and may struggle with the standard treatment for locally advanced rectal cancer, which typically includes chemoradiotherapy, surgery, and chemotherapy. While this approach shows good clinical results, it may not be suitable for all frail patients due to potential side effects. Since frail patients are underrepresented in clinical trials, this article highlights the need for new treatment strategies for them. Routine screening for frailty in hospitalized patients is recommended, and treatment should be planned by a multidisciplinary team, including specialists such as geriatricians and oncologists. Adapting guidelines and treatment plans for frail patients is crucial for improving outcomes in this growing population. Owing to the gradual aging of today's population, an increase in the prevalence of frailty syndrome has been noticed. This complex state of health, characterized by decreased resilience and tolerance with concurrent increased vulnerability to stressors and adverse health-related factors, has drawn researchers' attention in recent years. Rectal cancer, which constitutes ~30% of all colorectal cancers, is a disease noticeably related to the elderly. In its locally advanced form, it is conventionally treated with trimodal therapy—neoadjuvant chemoradiotherapy followed by total mesorectal excision and adjuvant chemotherapy. Despite its good clinical outcomes and improvement in rectal cancer local control, as evidenced by clinical trials, it remains unclear if all frail patients benefit from that approach since it may be associated with adverse side effects that cannot be handled by them. As old patients, and frail ones even more noticeably, are poorly represented in the clinical trials describing outcomes of the standard treatment, this article aims to review the current knowledge on the trimodal therapy of rectal cancer with an emphasis on novel approaches to rectal cancer that can be implemented for frail patients. [ABSTRACT FROM AUTHOR]

Background: Ureteral injury occurs in 0.3–1.5% of colorectal cancer surgeries. Devices to visualize the ureteral course and avoid ureteral injury are required for minimally invasive surgery (MIS). The NIRC™ fluorescent ureteral catheter (FUC) is a versatile ureteral visualization device currently available in Japan that can be used in combination with a variety of laparoscopic and robotic systems. In this study, we examined the outcomes of high-risk patients who underwent colorectal cancer surgery with FUC insertion. Methods: One hundred forty-one patients who underwent MIS for colorectal cancer and colorectal cancer recurrence at our institute between January 2021 and May 2024 underwent preoperative FUC insertion because of the high risk of ureteral injury and surgical difficulty. For these patients, patient background data and short-term outcomes were examined. The results are expressed as the median and interquartile range. Results: Age, 70 [60–78]; M:F(n), 84:57; BMI, 22.1 [19.7–24.7]; T4 (TNM classification), 52 cases (36.9%); preoperative intestinal obstruction, 45 cases (31.9%); abscess formation, 30 cases (21%); surgical history, 70 cases (50%); recurrent cancer, 14 cases (9.9%); preoperative chemo-radiotherapy, 28 cases (19.9%); time required for FUC insertion, 12 [9–19] minutes; operation time, 412 [309–552] minutes; blood loss, 10 [5–30] ml; open conversion, 0 cases; postoperative hospitalization, 12 [9–17.5]; circumferential resection margins < 1 mm (rectal surgery), 4/87 cases (4.6%); comorbidities, 0 ureteral injury, 1 urethral injury during FUC insertion (0.7%) and 16 CD Grade 3 or higher cases (11%). Conclusions: FUC may improve the safety of MIS and reduce blood loss in addition to preventing ureteral injury and is expected to have oncological advantages for ensuring the margin of the tumor without fear of ureteral injury. However, the time required for and complications associated with FUC are challenging. New methods for less invasive and easier ureteral visualization may be needed. [ABSTRACT FROM AUTHOR]

Objective: The Surgical Apgar Score quantifies three intraoperative parameters: lowest heart rate, lowest mean arterial pressure, and estimated blood loss (EBL). This scoring system predicts postoperative complications based on these measured factors. The aim of this study was to investigate the value of modified Surgical Apgar Score (mSAS) in predicting postoperative complications in patients with rectal cancer treated with robotic surgery in order to improve the survival and quality of life of rectal cancer patients. Methods: The study included patients with rectal cancer who underwent robotic surgery in the Department of Gastrointestinal Surgery at the First Affiliated Hospital of Nanchang University from January 2015 to December 2023. In minimally invasive surgery, we developed a modified Surgical Apgar Score (mSAS) tailored for robotic rectal cancer surgery, incorporating an adjusted threshold for EBL. This threshold was derived from quartile analysis of a cohort of 524 patients, with a median EBL of 100 mL (IQR 80–130 mL). We analyzed the association of postoperative complications with low mSAS. Results: This study included 524 patients, of which 91 (17.4%) experienced complications and 22 (4.2%) suffered severe complications. mSAS of 6 provided maximal Youden index and were determined as the cut-off values. The area under the ROC curve for predicting complications using the mSAS was 0.740. Univariate and multivariate analyses indicated that an older age, lower tumor localization, longer operation time, radiotherapy alone, combined chemoradiotherapy, and lower mSAS as independent risk factors for complications. The AUC of the prediction nomogram was 0.834 (95% CI 0.774–0.867). The calibration curve demonstrated excellent concordance with the nomogram, indicating the prediction curve ft the diagonal well. Conclusion: This study suggests that mSAS might be a valuable predictive indicator for postoperative complications following robotic rectal cancer surgery, with potentially higher clinical utility. [ABSTRACT FROM AUTHOR]

Background: This study explored the significance of consolidation maintenance chemotherapy after concurrent chemoradiotherapy with different regimens in patients with esophageal squamous cell carcinoma. Method: A prospective randomized controlled phase III clinical trial was designed and registered in the China Clinical Trials Registry (Registration number: ChiCTR‐TRC‐12002719). Survival data were analyzed in terms of intention‐to‐treat (ITT) and per‐protocol (PP) sets for patients undergoing cisplatin and 5‐fluorouracil (PF) (group A), or cisplatin and paclitaxel (TP) (group B). Results: The incidence risk of grade III–IV leukopenia in group B was higher than in group A (49.2% vs. 25.5%, p = 0.012). The survival rates at 1, 2, 3, and 5 years were 83.8%, 62.6%, 53.1%, and 41.3%, respectively. Consolidation chemotherapy after concurrent chemoradiation therapy had no benefit on median progression‐free survival (PFS) (p = 0.95) and overall survival (OS) (p = 0.809). According to the ITT analysis, the median PFS in group A and group B was 28.6 months and 30.3 months (X2 = 0.242, p = 0.623), while the median OS was 31.0 months and 50.3 months (X2 = 1.25，p = 0.263). For the PP analysis, the median PFS in group A and group B were 28.6 months and 30.3 months (p = 0.584), while the median OS was 31.0 months and 50.3 months (p = 0.259), respectively. Patients receiving consolidation chemotherapy did not show significant OS benefits (46.9 months vs. 38.3 months; X2 = 0.059, p = 0.866). Conclusion: Similar PFS and OS were found between PF and TP regimens with concurrent chemoradiotherapy. Consolidation chemotherapy did not show any significant OS benefits. [ABSTRACT FROM AUTHOR]

Tumour response assessments, as per Response Evaluation Criteria in Solid Tumours (RECIST 1.1), are based on the sum of diameters (SODs) of the primary tumour (longest diameter) and/or short axis diameter of lymph nodes. This study evaluates the response categorisation as per RECIST 1.1 vs Computed tomography (CT) based volumetric assessment of RECIST (proposed as vRECIST) in locally advanced head and neck cancers (LAHNCs) undergoing treatment. The pre-treatment SODs and CT estimated tumour volumes were recorded in 45 LAHNCs treated with radiotherapy (RT), chemoradiotherapy (CTRT) or thermochemoradiotherapy (HTCTRT). Tumour responses were assessed independently as per RECIST 1.1 and vRECIST by two radiation oncologists and grouped into complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD). These response groups were evaluated for the likely congruence of the two approaches, as categorised independently by these two observers. All patients in stages III (n = 7), IVA (n = 16) and IVB (n = 22) were inoperable and had received either RT alone (n = 1), CTRT (n = 12) or HTCTRT (n = 32). Based on SODs criteria of RECIST 1.1, of the 45 patients, 5 and 40 were grouped as PR and SD by the first observer, while this changed to 34 and 10, respectively and 1 PD, with vRECIST (p < 0.001). Similarly, for the second observer, the 4 PR and 41 SD grouped using RECIST 1.1 were recategorised to 34 PR, 10 SD, and 1 PD by vRECIST (p < 0.001). Thus, a mismatch of 66. 6% and 68. 8%, respectively, was evident by observers first and second in categorising SD based on SODs of RECIST 1.1 vs PR on vRECIST. Treatment responses in LAHNCs assessed using SODs resulted in significant uncertainties and failed to reflect actual volumetric changes in tumours during treatment. It is perhaps time to consider replacing the SODs of RECIST 1.1 with vRECIST for unequivocal tumour response categorisation in the present era of image-based oncology practice. • Tumour responses are assessed on %reduction in the sum of diameters (SODs) as per RECIST 1.1. • Pre- and post-treatment tumour volumes on computed tomography (CT) were evaluated for tumour response. • Gross mismatches in response categories grouped by SOD vs tumour volume were evident. • Revision of tumour response assessment criteria of RECIST 1.1 is strongly desirable. • Suggest to replace SOD with target volume (vRECIST) for tumour response assessments. [ABSTRACT FROM AUTHOR]

Alveolar rhabdomyosarcoma (ARMS) is a rare but highly aggressive cancer predominantly affecting children and adolescents. This study explores prognostic factors for pediatric and adolescent ARMS, using the Surveillance, Epidemiology, and End Results (SEER) database. Leveraging SEER data (2000-2019), we analyzed 277 cases. Employing Kaplan-Meier survival analysis and Cox proportional hazards models, we identified significant prognostic factors. Gender distribution was nearly equal (56.0% boys, 44.0% girls), with the majority (70.8%) from the white ethnic group. Primary tumors were predominantly in extremities (37.2%). Distant metastases significantly increased mortality risk (hazard ratio [HR], 3.13; 95% CI: 2.14-4.58) and regional lymph node involvement raised mortality risk (HR, 1.36; 95% CI: 0.96-1.92). Chemotherapy-only treatment had higher mortality risk than chemoradiotherapy (HR, 1.16; 95% CI: 0.97-2.67). Conclusively, our study identifies distant metastases, regional lymph node involvement, and treatment modality as crucial predictors of overall survival in pediatric ARMS. [ABSTRACT FROM AUTHOR]

The standard of care for the treatment of locally advanced rectal cancer (LARC) results in an excellent local disease control but the metastasis rates remain high. PRODIGE 23 demonstrated improved disease-free survival (DFS) and metastasis-free survival (MFS) with total neoadjuvant therapy versus standard of care in this population. Long-term analysis of overall survival (OS) is reported here. The study design, participants, and primary endpoint DFS have been reported for this multicenter, randomized, open-label, phase III trial investigating the neoadjuvant chemotherapy with mFOLFIRINOX (6 cycles) followed by chemoradiotherapy, surgery, and adjuvant chemotherapy (6 cycles), versus chemoradiotherapy, surgery, and adjuvant chemotherapy (12 cycles) in patients with locally advanced rectal adenocarcinoma under peritoneal reflection on magnetic resonance imaging, and staged cT3/T4. Key secondary endpoints included OS, MFS, and local and metastatic recurrence rate. With a median follow-up of 82.2 months, the 7-year DFS was 67.6% [95% confidence interval (CI) 60.7% to 73.9%] and 62.5% (95% CI 55.6% to 68.6%) [restricted mean survival time (RMST) difference 5.73 months, 95% CI 0.05-11.41 months, P = 0.048] in the neoadjuvant chemotherapy and the standard-of-care groups, respectively. The 7-year MFS was 79.2% (95% CI 73.0% to 84.4%) in the neoadjuvant chemotherapy group and 72.3% (95% CI 65.8% to 77.8%) in the standard-of-care group (RMST difference 6.1 months, 95% CI 0.93-11.37 months, P = 0.021). The 7-year OS was 81.9% (95% CI 75.8% to 86.6%) in the neoadjuvant chemotherapy group and 76.1% (95% CI 69.7% to 81.2%) in the standard-of-care group (RMST difference 4.37 months, 95% CI 0.35-8.38 months, P = 0.033). The safety profile remained unchanged since the previous analysis. Neoadjuvant chemotherapy with mFOLFIRINOX followed by chemoradiotherapy improved OS, confirmed long-term DFS and MFS benefits in LARC patients, and should be considered as one of the best options of care for these patients. • With standard-of-care trimodality therapy for LARC, the 5-year metastasis rate is 25%-35%. • PRODIGE 23 investigated mFOLFIRINOX induction chemotherapy before standard of care, versus standard of care for LARC. • With 7 years of follow-up, induction chemotherapy significantly improved MFS. • DFS and OS were also significantly improved using mFOLFIRINOX induction chemotherapy. [ABSTRACT FROM AUTHOR]

There is growing evidence to suggest that radiotherapy might enhance the efficacy of immunotherapy. This study aimed to assess the possibility of KN046, a bispecific antibody targeting PD-L1 and CTLA-4, combined with chemotherapy and palliative radiotherapy for advanced esophageal squamous cell carcinoma (ESCC). In this open-label, phase Ib trial, patients with advanced ESCC were administered chemotherapy with palliative radiotherapy, and KN046 in the predefined escalation dosages of 1, 3, or 5 mg/kg (every 3 weeks during chemotherapy cycles and every 2 weeks during KN046 maintenance). The chemotherapy regimen constituted cisplatin (75 mg/m2 i.v., d1) and paclitaxel (135–175 mg/m2 ivgtt., d1). Radiotherapy specifics, including site, timing, dose, and fragmentation pattern, were at the investigator’s discretion. The primary outcome was dose-limiting toxicity (DLT). From May 2019 to April 2021, 25 patients were enrolled across the dosage groups: 3 in 1 mg/kg, 12 in 3 mg/kg, and 10 in 5 mg/kg. No DLT was observed during the dose escalation. The objective response rate was 41.7% (95%CI 22.1–63.4), while the disease control rate was 87.5% (95%CI 67.6–97.3). At a median follow-up of 11.8 months, the median progression-free survival was 7.8 months (95%CI 5.2–9.7) and median overall survival was 15.9 months (95%CI 8.4-NE). Serious adverse events were reported in 48.0% of patients, predominantly leukopenia (16%), immune-mediated enterocolitis (12%), immune-mediated pneumonitis (8%), and neutropenia (8%). Combining KN046 with chemotherapy and palliative radiotherapy might be feasible, showing a favorable safety profile and notable efficacy in advanced ESCC patients. [ABSTRACT FROM AUTHOR]

Measuring tissue oxygen concentration is crucial in understanding the pathophysiological process of hypoxia in head and neck cancer (HNC) and its significant role in cancer biology. This study aimed to determine the feasibility of T1 mapping using a variable flip angle (VFA) technique with stack of stars (SOS) trajectory sampling in HNC patients undergoing chemoradiotherapy (CRT). To evaluate the ability of SOS acquisition to detect T1, a phantom study was conducted and compared to conventional Cartesian acquisition (CART). Additionally, four newly diagnosed patients were recruited and underwent two scans each at baseline and inter-treatment. The repeatability of SOS and CART acquisitions was assessed by comparing the T1 measurements of CSF from the baseline and intra-treatment MRI studies. The changes in ∆T1 of the tumors during air and oxygen inhalation between baseline and inter-treatment scans were also evaluated. Our study found that the 3D VFA SOS sequence was effective in reducing motion artifacts compared to the conventional VFA sequence with CART sampling and the same scan time, as demonstrated by the results from the phantom and patient studies. In terms of repeatability, no significant correlation was observed between the variability in ΔT1 measurements of CSF obtained from SOS T1 maps. The SOS ΔT1 measurements showed higher consistency, as evidenced by the ICC values ranging from 0.52 to 0.92. The ∆T1 measurements on the primary tumors increased after the first CRT (p<0.05) for all patients who showed a positive treatment response, except for one patient (0.05

Background Chemoradiotherapy (CRT) with high-dose cisplatin (CDDP) is the standard treatment for locally advanced head and neck squamous cell carcinoma (HNSCC). Although dosing is based on body surface area (BSA), some patients experience CDDP-related adverse events (AEs). We aimed to evaluate the impact of relative CDDP dose to skeletal muscle mass (SMM) on chemotherapy-associated AEs in patients with HNSCC undergoing CRT with high-dose CDDP. Materials and Methods We retrospectively analyzed data of patients who underwent CRT with high-dose CDDP (80-100 mg/m2, triweekly) between 2010 and 2023. SMM was measured as the cross-sectional muscle area at the third cervical vertebra (C3-SMM) using computed tomography; the skeletal muscle index (SMI) was defined as SMM normalized by squared height. The CDDP index was defined as the prescribed CDDP dose divided by SMI. CDDP-related AEs were assessed during the first cycle using Common Terminology Criteria for Adverse Events v5.0. Results Overall, 306 patients were identified. The CDDP index cutoff value best associated with grade ≥ 3 AEs was 10.312. Grade ≥ 3 hematological toxicities exhibited stronger association with high CDDP index value than with low CDDP index value (26.9% vs 16.3%, P  = .033). Multivariate analysis revealed that high CDDP index value and creatinine clearance < 70 mL/minute were predictive factors for grade ≥ 3 AEs (odds ratio [OR] 2.55, P  = .008; OR 3.68, P  = .002, respectively). Conclusion The CDDP index based on C3-SMM was an independent predictive factor for grade ≥ 3 CDDP-related AEs. C3-SMM is potentially more useful than BSA for determining the optimal CDDP dose in patients with HNSCC. [ABSTRACT FROM AUTHOR]

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Background: This study aimed to investigate the clinical benefit of adding concurrent chemotherapy to intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) patients with an intermediate risk (stage II and T3N0M0). Methods: A multicenter phase II randomized trial was conducted in intermediate-risk NPC patients. Enrolled patients were previously untreated and aged ranged from 18 to 70 years without severe coexisting diseases. Patients were randomly assigned to receive IMRT alone or IMRT+concurrent chemotherapy (CC; three cycles of 80 mg/m2 cisplatin every 3 weeks). Primary endpoint was defined as 3‑year progression-free survival (PFS). The secondary endpoints were distant metastasis-free survival (DMFS), locoregional relapse-free survival (LRRFS), overall survival (OS), and treatment-associated toxicity. We registered this study with Chinese Clinical Trial Registry (CliCTR1800017132; registered July 13, 2018, study start July 13, 2018). Results: From November 2015 to July 2019, 42 patients with stage II and T3N0M0 NPC were enrolled; 20 patients received IMRT alone while 22 patients received IMRT+CC. After a median of 58 months of follow-up, we estimated the 3‑year PFS rates as 90% (IMRT group) and 86.4% (IMRT+CC group; hazard ratio 1.387, 95% confidence interval 0.240–8.014; P = 0.719). The 3‑year PFS, OS, and cumulative DMFS and LRRFS showed no significant differences between the two groups (P > 0.05). However, the IMRT group displayed a lower incidence of nausea/vomiting, leucopenia, and dry mouth than the IMRT+CC group. Conclusion: Adding CC to IMRT provided no survival benefit but increased treatment-associated toxicities in patients with intermediate-risk NPC. [ABSTRACT FROM AUTHOR]

Background: In patients with locally advanced esophageal cancer who had undergone chemoradiotherapy (CRT), the limitations of radiological evaluation may necessitate surgical exploration to ascertain disease resectability. Upon intraoperative confirmation of T4b disease (sT4b), the optimal management strategy remains unclear. While some surgeons may opt against resection, others advocate for palliative esophagectomy (PE). Regrettably, the current literature does not provide a consensus on the most effective approach for managing these intricate cases. Methods: The study cohort consisted of 68 patients with esophageal squamous cell carcinoma (ESCC) who presented with sT4b disease following CRT. The perioperative outcomes and overall survival (OS) were compared between patients who underwent PE (n = 56) and those who received an open-close (OC) procedure (n = 12). Results: Patients who underwent an OC procedure experienced a shorter hospital stay (16.5 vs. 28.8 days; p = 0.052) and showed a non-significant reduction in the rate of major complications (33.9% vs. 25%; p = 0.549) and in-hospital mortality (0% vs. 5.4%; p = 0.412) than those who received PE; however, PE was associated with a superior 2-year OS rate than OC (9.6% vs. 0%; p = 0.009). In multivariable analysis, a pretreatment clinical stage of II/III (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.31−0.87; p = 0.013) and PE with retrosternal reconstruction (HR 0.38, 95% CI 0.15−0.49; p = 0.010) were independently associated with a more favorable OS. Conclusion: PE with retrosternal reconstruction may be a feasible approach for patients with ESCC exhibiting sT4b disease after CRT. [ABSTRACT FROM AUTHOR]

Purpose. To evaluate the predictive potency of a novel index combining the pan‐immune‐inflammatory index and hemoglobin levels (PIV/Hb) for the prevalence of radiation‐induced trismus (RIT) in patients with locally advanced nasopharyngeal cancer (LA‐NPC) receiving concurrent chemoradiotherapy (CCRT). Methods. Data from 228 LA‐NPC patients were retrospectively examined. Maximum mouth openings (MMO) were measured to confirm the presence of RIT, defined as MMOs ≤35 mm. Complete blood test results from the first day of CCRT were used to calculate PIV/Hb levels. A potential relationship between pretreatment PIV/Hb and the RIT status was evaluated using receiver operating characteristic (ROC) curve analysis. Results. Post‐CCRT RIT was diagnosed in 20.2% of the patients. The ROC curve analysis determined 68.4 g/dL as the ideal PIV/Hb cutoff that effectively divided patients into two distinct groups (area under the curve: 94.7%; specificity: 86.4%; sensitivity: 87.4%). RIT was significantly more prevalent in the PIV/Hb > 68 group than in the PIV/Hb < 68 group (58.8% vs. 3.8%; P < 0.001). Multivariate logistic regression analysis showed that a pre‐CCRT PIV > 68 was independently associated with significantly higher rates of RIT. Conclusion. Higher pretreatment levels of the novel PIV/Hb index predict increased RIT rates following definitive CCRT for LA‐NPCs. [ABSTRACT FROM AUTHOR]

Background: This study aims to delineate the long-term outcomes and recurrence patterns of locally advanced thoracic esophageal squamous cell carcinoma (TESCC) patients managed with or without postoperative radiotherapy (PORT). Methods: A retrospective cohort from two academic centers, encompassing patients who initially underwent esophagectomy and were pathologically staged T3-4, was analyzed. Survival outcomes were constructed using Kaplan–Meier method, with survival significance was evaluated using the log-rank test. Propensity score matching (PSM) was utilized to balance potential selection bias. Results: Among the 506 patients, 251 underwent surgery alone and 255 received radiotherapy following radical surgery. With a median follow-up of 49.1 months, PORT significantly improved 5-year overall survival (53.8% vs. 25.3%; p < 0.001) and 5-year disease-free survival rates (45.3% vs. 8.5%; p < 0.001) compared to surgery alone. These differences in survival outcomes persisted even after PSM (p < 0.001 for both). Treatment failure was significantly less frequent in the PORT group (46.7%) compared to the surgery-only group (90.0%; p < 0.001), with corresponding reductions in locoregional recurrence (9.4% vs. 54.1%; p < 0.001). This underscores the significant association between PORT and disease control. Conclusion: The absence of neoadjuvant chemoradiotherapy highlights the importance of PORT in improving survival and reducing recurrence in advanced T3-4 TESCC patients. This study underscores the importance of PORT as a salvage treatment for locally advanced TESCC patients without neoadjuvant chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Introduction: This is a prospective, rigorous inquiry into the systemic immune effects of standard adjuvant chemoradiotherapy, for WHO grade 4, glioblastoma. The purpose is to identify peripheral immunologic effects never yet reported in key immune populations, including myeloid-derived suppressor cells, which are critical to the immune suppressive environment of glioblastoma. We hypothesize that harmful immune-supportive white blood cells, myeloid derived suppressor cells, expand in response to conventionally fractionated radiotherapy with concurrent temozolomide, essentially promoting systemic immunity similar what is seen in chronic diseases like diabetes and heart disease. Methods: 16 patients were enrolled in a single-institution, observational, immune surveillance study where peripheral blood was collected and interrogated by flow cytometry and RNAseq. Tumor tissue from baseline assessment was analyzed with spatial proteomics to link peripheral blood findings to baseline tissue characteristics. Results: We identified an increase in myeloid-derived suppressor cells during the final week of a six-week treatment of chemoradiotherapy in peripheral blood of patients that were not alive at two years after diagnosis compared to those who were living. This was also associated with a decrease in CD8+ T lymphocytes that produced IFNg, the potent anti-tumor cytokine. Discussion: These data suggest that, as in chronic inflammatory disease, systemic immunity is impaired following delivery of adjuvant chemoradiotherapy. Finally, baseline investigation of myeloid cells within tumor tissue did not differ between survival groups, indicating immune surveillance of peripheral blood during adjuvant therapymay be a critical missing link to educate our understanding of the immune effects of standard of care therapy for glioblastoma. [ABSTRACT FROM AUTHOR]

Esophagogastric adenocarcinoma (EGJ‐AC) poses a significant global health burden, characterized by high incidence rates and poor prognosis. Despite advancements in treatment modalities, including surgery, chemotherapy, and radiation therapy (RT), locally advanced EGJ‐AC management remains challenging. Various preclinical and clinical studies have provided insights into the synergistic effects of combining immune checkpoint inhibitors (ICIs) with RT, further supporting the combination therapy in EGJ‐AC. Immunotherapy, particularly ICIs, has emerged as a promising therapeutic approach in various malignancies, including EGJ‐AC. This narrative review aims to critically examine the rationale behind combining ICIs with standard treatment modalities, including RT or chemoradiotherapy, in the preoperative setting for locally advanced EGJ‐AC. A comprehensive literature search identified eight phase 2 randomized clinical trials evaluating the safety profile and oncologic outcomes of adding ICI agents to neoadjuvant chemoradiotherapy in this population. The results of enrolled trials show that the combination of ICIs with standard treatment modalities is a promising approach for improving survival and pathological response in patients with locally advanced EGJ‐AC. This combination treatment was associated with mostly grade 1–2 immune‐related toxicities, indicating its safety and tolerability. There were higher rates of complete or major pathologic responses compared to historical controls. Further studies, including large‐scale randomized controlled trials, are needed to address remaining questions regarding the efficacy, safety, and long‐term outcomes of combination therapy in this population. [ABSTRACT FROM AUTHOR]

Podocalyxin-like protein (PODXL) is known to originate from tumor cells in several cancers; however, which cell type it is expressed in, whether and how it may contribute to tumor progression after radiotherapy or chemoradiotherapy in cervical cancer (CC) remain unknown. In this study, we investigated these issues using a cohort of 180 immune stain data, single-cell RNA sequencing (scRNA-seq) data of 29,453 cells, and bulk RNA sequencing data from 187 cervical cancer samples treated with radiotherapy or chemoradiotherapy. ScRNA-seq analysis revealed that PODXL was predominantly expressed in tumor endothelial cells (TECs) of CC, which was corroborated by tumor section staining. Moreover, the PODXL expression level was negatively associated with progression-free survival and overall survival of 180 CC patients receiving radiotherapy or chemoradiotherapy (both p < 0.001). Furthermore, compared with PODXLlow TECs, PODXLhigh TECs exhibited a diminished anti-tumor immune response and enhanced tumor-promoting features characteristics. In addition, PODXL over-expression was also found to be negatively associated with immune response and indicated poor survival in bulk RNA sequencing data of CC treated with radiotherapy or chemoradiotherapy. These results underscore the role of PODXL in CC, suggesting it as a promising target and prognostic marker for patients treated with radiotherapy or chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Background: Image guidance is recommended for patients undergoing intensity‐modulated radiation therapy (IMRT) for cervical cancer. In this study, we evaluated the feasibility of a weekly image guidance pattern and analyzed the long‐term outcomes in a large cohort of patients. Methods: The study enrolled patients with Stage IB‐IVA cervical cancer who received definitive radiotherapy or concurrent chemoradiotherapy. IMRT was delivered at a dose of 50.4 Gy in 28 fractions, with weekly cone‐beam computed tomography (CBCT). Physicians advised patients on rectum and bladder preparation to help them prepare on nonimaging guidance days. When significant tumor regression was observed, a second computed tomography simulation and replanning were performed. Results: The median follow‐up periods were 63.4 months. The incidence rates of loco‐regional and distant failure were 9.9% and 13.6%. The 5‐year overall survival (OS), disease‐free survival (DFS), loco‐regional relapse‐free survival (LRFS), and distant metastasis‐free survival (DMFS) rates were 80.1%, 72.9%, 78.3%, and 74.8%, respectively. For patients with different stages, the 5‐year OS, DFS, LRFS, and DMFS rates were statistically significant. For patients with and without positive regional lymph nodes, the 5‐year OS, DFS, LRFS, and DMFS rates were 64.5% and 86.0%, 56.8% and 78.8%, 62.7% and 84.3%, and 58.8% and 81.0%, respectively. Multivariate analysis showed that age, histology, tumor size, cancer stage, pretreatment squamous cell carcinoma antigen level, and para‐aortic metastatic lymph nodes were independent prognostic factors of OS. Fifty‐six (4.0%) patients experienced late Grade 3/4 chronic toxicities. Conclusions: IMRT with weekly CBCT is an acceptable image guidance strategy in countries with limited medical resources. [ABSTRACT FROM AUTHOR]

Background: In a randomized phase II/III trial (JCOG1008), weekly cisplatin (40 mg/m2) was non‐inferior to 3‐weekly cisplatin (100 mg/m2) for postoperative high‐risk head and neck cancer. We investigated how acute kidney injury (AKI), a major dose‐limiting toxicity effect of cisplatin, affects overall survival (OS). Methods: We analyzed 251 patients from JCOG1008 receiving chemoradiotherapy. AKI was defined based on AKI Network criteria (serum creatinine increase of ≥0.3 mg/dL or ≥1.5‐fold [≥ stage I]) within 30 days after completing chemoradiotherapy. OS in the two arms was compared according to AKI development using the log‐rank test. Results: The total incidence of AKI was lower in the weekly arm than in the 3‐weekly arm (38/122 [31.1%] vs. 56/129 [43.4%]). Additionally, stage II/III AKI occurred less frequently in the weekly arm than in the 3‐weekly arm (8/122 [6.6%] vs. 19/129 [14.7%]). Cisplatin doses were similar in the weekly arm for patients with and without AKI (median, 238.6 mg/m2 vs. 239.2 mg/m2; p = 0.94), but lower in the 3‐weekly arm for those who developed AKI (median, 276.3 mg/m2 vs. 297.4 mg/m2; p = 0.007). In the weekly arm, there was no difference in OS between patients with and without AKI (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.53 to 2.10). However, in the 3‐weekly arm, patients with AKI had poorer OS than those without AKI (HR, 1.83; 95% CI, 1.04 to 3.21). Conclusions: In this supplementary analysis of JCOG1008 data, AKI impacted the OS of patients with head and neck cancer undergoing postoperative chemoradiotherapy in the 3‐weekly arm but not in the weekly arm. Our results further endorse the utilization of weekly cisplatin at 40 mg/m2 in this setting. [ABSTRACT FROM AUTHOR]

Objective: The optimal management of rectal cancer remains a subject of ongoing research. This meta-analysis of individual patient data assessed the benefit of chemoradiotherapy (fluorouracil-based) in local advanced rectal cancer: disease-free survival and overall survival. Methods: We pooled the data of 6145 patients from 24 studies of rectal cancer who received neoadjuvant radiotherapy with concomitant fluorouracil or capecitabine and surgery. The PRISMA 2020 abstract checklist was followed. Individual participant survival was reconstructed with an algorithm from published Kaplan–Meier curves. Results: The median OS was not reached; the mean survival time was 135.4 months (127.9–141.5). The median DFS was 176.9 months, and the mean disease-free survival time was 122.6 months (111.7–131.9). Conclusions: We provided a benchmark for future studies on rectal cancer treatment. The present results can be used in decision-making for locally advanced rectal cancer patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Real-world studies comparing TNT and CRT are vital for advancing the treatment of LARC. Our study provides valuable insights reflecting the diverse patient populations and varied clinical practices encountered and demonstrates the advantage of TNT, providing a superior alternative to standard CRT and potentially enhancing treatment outcomes and quality of life. Total neoadjuvant therapy (TNT) has emerged as a promising approach for managing locally advanced rectal cancer (LARC), aiming to enhance resectability, increase pathological complete response (pCR), improve treatment compliance, survival, and sphincter preservation. This study compares the clinical outcomes of TNT, with either induction or consolidation chemotherapy, to those of the standard chemoradiotherapy (CRT). In this retrospective multi-institutional study, patients with stage II-III LARC who underwent CRT or TNT from seven oncology centers between 2021 and 2024 were retrospectively analyzed. The TNT group was categorized into induction or consolidation groups based on the sequence of chemotherapy and radiotherapy. Clinical and pathological data and treatment outcomes, including pCR, event-free survival (EFS), and overall survival (OS), were analyzed. Among the 276 patients, 105 received CRT and 171 underwent TNT. The TNT group showed significantly higher pCR (21.8% vs. 2.9%, p < 0.001) and lower lymphatic (26.3% vs. 42.6%, p = 0.009), vascular (15.8% vs. 32.7%, p = 0.002), and perineural invasion rates (20.3% vs. 37.6%, p = 0.003). Furthermore, 16.9% of TNT patients opted for non-operative management (NOM), compared to 0.9% in the CRT group (p < 0.001). The median interval between the end of radiotherapy and surgery was longer in the TNT group (17.6 weeks vs. 8.8 weeks, p < 0.001). The 3-year EFS was 58.3% for CRT and 71.1% for TNT (p = 0.06). TNT is associated with higher pCR, lower lymphatic and vascular invasion rates, and higher rates of NOM compared to CRT. This supports the use of TNT as a viable treatment strategy for LARC, offering potential benefits in quality of life. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with high-grade gliomas have a poor prognosis, with a median survival of only 11–18 months from the initial diagnosis after standard treatment. Surgery and chemoradiation are the first-line treatment strategies for malignant gliomas, but achieving durable local tumor control is a major challenge due to the pervasive infiltrative nature of gliomas, their growth rate, and their recurrence rate. Gadolinium-enhanced magnetic resonance imaging (MRI) is currently the primary imaging technique for high-grade gliomas; however, it has limitations, including difficulty in differentiating between tumor recurrence and treatment-induced changes, as well as challenges in accurately assessing total tumor volume due to the restricted sensitivity of gadolinium contrast. It is therefore worth looking for alternative imaging modalities that can overcome these limitations. Positron emission tomography (PET) is one of them. To this end, the identification of PET-based markers that can be used in the imaging of high-grade gliomas is of paramount importance. 11C-Methionine (MET) is a widely utilized amino acid tracer in positron emission tomography (PET) imaging of primary brain tumors. 11C-MET PET offers valuable insights for tumor classification, facilitates treatment planning, and aids in monitoring therapeutic response. Its tracer properties allow better delineation of the active tumor volume, even in regions that show no contrast enhancement on conventional magnetic resonance imaging (MRI). This review focuses on the role of MET-PET in brain glioma imaging. The introduction provides a brief clinical overview of the problems of high-grade and recurrent gliomas. It discusses glioma management, radiotherapy planning, and the difficulties of imaging after chemoradiotherapy (pseudoprogression or radionecrosis). The mechanism of MET-PET is described. Additionally, the review encompasses the application of MET-PET in the context of primary gliomas, addressing its diagnostic precision, utility in tumor classification, prognostic value, and role in guiding biopsy procedures and radiotherapy planning. [ABSTRACT FROM AUTHOR]

Simple Summary: Approximately 40% of all diagnoses of rectal cancer in Spain are locally advanced. A multimodal treatment is needed, and one of its pillars is radiotherapy, with a classic dose scheme of up to 50–50.4 Gy concomitantly with oral capecitabine or 5-fluorouracil. Dose escalation is being explored to achieve higher rates of a pathological complete response, but the optimal dose and its impact on the outcomes are unclear. Our study aimed to evaluate the percentage of complete pathological responses obtained with an intensified neoadjuvant radiotherapy treatment scheme. We confirmed in a homogeneous population (49 patients treated with standard radiotherapy vs. 50 patients treated with dose-escalated radiotherapy) higher rates of a pathological complete response with a dose of up to 54 Gy concomitantly with oral capecitabine. Neoadjuvant radiotherapy intensification is useful for specimen sterilization and should be offered to selected patients. Locally advanced rectal cancer requires a multimodal treatment. Radiotherapy is being explored for intensification to improve the rates of pathological complete responses (ypCR rates) which are correlated with better outcomes. This study reports a comparison between standard versus escalated doses in a preoperative scenario. The ypCR rates, toxicity, postoperative complications, and disease-free and overall survival at 5 years are described. From 2012 to 2019, 99 patients were analyzed retrospectively: standard arm (mean of 47.5 Gy) vs. dose-escalated arm (mean of 54.3 Gy). All patients were treated with 3DRT in 25 fractions, with concomitant capecitabine and surgery performed according to the total mesorectal excision principles in both arms. The ypCR was reported using the "College of American Pathologist grades"; the gastrointestinal (GI) and genitourinary (GU) toxicity was reported using the "Common Terminology Criteria for Adverse Events" (CTCAE 4.0). The ypCR rates were higher in the dose-escalated group (25% vs. 10.64%; p = 0.07), with a lower rate of non-treatment response (61.36% vs. 38.64%; p = 0.11). No statistical differences between the arms were found in terms of the oncological outcomes, postoperative complications (p = 0.15), second surgeries (p = 0.62), or deaths (p = 0.62). The CTCAE acute GI and GU toxicity were grade I or II in both arms. Our study presents a long-term follow-up in comparative cohorts. [ABSTRACT FROM AUTHOR]

Simple Summary: This research highlights the differences in genetic mutations between primary tumors and their subsequent spine metastases. These distinctions are relevant to neurosurgeons because effective surgical planning and goals rely on factors such as patient prognosis, which is impacted by tumor genetic markers. Certain genetic markers may be more or less favorable, thus impacting the predicted patient treatment course and prognosis. The authors aim to present an overview of these complex molecular characteristics for neurosurgical oncology providers. The content of this review is intended to assist neurosurgeons' decision-making when caring for spinal oncology patients and to illustrate the importance of multidisciplinary management of this complex patient population. For many spine surgeons, patients with metastatic cancer are often present in an emergent situation with rapidly progressive neurological dysfunction. Since the Patchell trial, scoring systems such as NOMS and SINS have emerged to guide the extent of surgical excision and fusion in the context of chemotherapy and radiation therapy. Yet, while multidisciplinary decision-making is the gold standard of cancer care, in the middle of the night, when a patient needs spinal surgery, the wealth of chemotherapy data, clinical trials, and other medical advances can feel overwhelming. The goal of this review is to provide an overview of the relevant molecular biomarkers and therapies driving patient survival in lung, breast, prostate, and renal cell cancer. We highlight the molecular differences between primary tumors (i.e., the patient's original lung cancer) and the subsequent spinal metastasis. This distinction is crucial, as there are limited data investigating how metastases respond to their primary tumor's targeted molecular therapies. Integrating information from primary and metastatic markers allows for a more comprehensive and personalized approach to cancer treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung cancer remains a leading cause of death despite advancements in treatment. A recent phase III trial has shown that adding an immune checkpoint inhibitor (ICI) to standard chemoradiation therapy (CCRT) improves survival in patients with advanced lung cancer. A sub-analysis of the same study also showed that shortening the interval between CRT and ICI increased the clinical benefits. Therefore, a feasibility study of nivolumab plus CCRT was conducted in Japanese patients with unresectable locally advanced NSCLC. We enrolled 12 patients and examined 10 for dose-limiting toxicities (DLT). The treatment was considered feasible if DLT occurred in three or fewer of the ten evaluable patients, meeting the study criteria. The findings suggest that nivolumab combined with CCRT is a safe and promising treatment option for patients with previously untreated unresectable locally advanced NSCLC, potentially improving their chances of survival. Despite advancements in diagnosing and treating non-small cell lung cancer (NSCLC), the prognosis remains poor. Immune checkpoint inhibitors have shown promise in enhancing survival rates. Therefore, this study aimed to investigate the safety of nivolumab administration with concurrent chemoradiation therapy (CCRT) in patients with unresectable locally advanced NSCLC. Twelve patients with unresectable locally advanced NSCLC at Kansai Medical University Hospital and Izumi City General Medical Center were enrolled from May 2018 to September 2020. They received nivolumab (360 mg) tri-weekly twice, weekly carboplatin (AUC 2 min × mg/mL) and paclitaxel (40 mg/m2) for 6 weeks, and thoracic radiotherapy (60 Gy/30 fractions), followed by maintenance nivolumab therapy (360 mg, tri-weekly) for 6 months. The primary endpoint was incidence of dose-limiting toxicities (DLTs), and the secondary endpoints included safety, response rate, progression-free survival (PFS), overall survival (OS), 2-year survival rate, and treatment completion rate. Three patients completed the protocol. Nine discontinued due directly to interstitial pneumonia (three) and pneumonia (one). Ten patients (83.3%) experienced a grade 3 or higher event, of which three (25%) experienced a grade 4 or higher event, and of these, one (8.3%) experienced a grade 5 event. Three patients experienced DLTs. Concurrent nivolumab with CCRT was tolerated in unresectable locally advanced NSCLC, which offers potential treatment benefits. [ABSTRACT FROM AUTHOR]

Combination of immunotherapy with radiotherapy is under active investigation. The PACIFIC trial firmly established the treatment paradigm of consolidation immunotherapy following definitive chemoradiotherapy, inspiring a series of similar or exploratory combination regimens. This summary highlighted six reports updated in the 2024 ASCO Annual Meeting. [ABSTRACT FROM AUTHOR]

To improve local disease control, the use of preoperative radiotherapy either alone or combined with chemotherapy has become standard practice in rectal cancer, but it is unclear how these treatments modify the antitumoral immune response. We aimed to evaluate tumor histopathologic features and the prognostic effect of host immune response in rectal cancer with variable treatment modalities. Ninety‐five rectal cancers with short‐course radiotherapy (SRT), 97 with long‐course chemoradiotherapy (CRT), and 154 without preoperative treatments, were evaluated for histopathologic features including Crohn's‐like reaction (CLR). CD3+ and CD8+ immunohistochemistry and tumor cells were analyzed from tumor tissue microarray samples to calculate T‐cell densities and G‐cross function values to estimate cancer cell–T‐cell co‐localization (proximity score). We found that lymphocyte densities were diminished after SRT, but CLR was scarcer after CRT. Proximity score and CLR density were prognostic for survival in cancer without preoperative treatments and could be combined into an enhanced prognostic score (immune grade). In the irradiated tumors, CLR density remained prognostic while the impact of T‐cell infiltration was insufficient alone. In multivariable analysis, the immune grade proved to be an independent prognostic factor for survival. In conclusion, the immune contexture of rectal cancer harbors prognostic significance even after preoperative radiotherapy. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Concurrent chemoradiotherapy is the standard therapy for locally advanced non‐small cell lung cancer (NSCLC). However, there is little evidence supporting its use in older adults. Low‐dose daily carboplatin combined with thoracic radiotherapy is considered a standard regimen for this population. To establish a simple and feasible carboplatin administration method, we conducted a study of weekly carboplatin and concurrent radiotherapy for older adults with locally advanced NSCLC.This prospective, single‐arm, multicenter, phase II clinical trial included patients aged ≥75 years with unresectable stage III NSCLC and Eastern Cooperative Oncology Group performance status 0–1. Patients received chemoradiotherapy (60 Gy/30 fractions plus concurrent weekly carboplatin at an area under curve of 2 mg mL−1 min−1). The primary endpoint was the overall response rate (ORR). Key secondary endpoints included progression‐free survival (PFS), overall survival (OS), and safety.From July 2020 to June 2022, 37 patients were enrolled from 15 institutions, and 36 patients were evaluable for efficacy and safety. The ORR was 63.9% (95% confidence interval [CI] = 47.6–77.5). Median PFS was 14.6 months (95% CI = 9.1–18.1). Median OS was 25.5 months (95% CI = 17.4–not reached). Grade 4 leucopenia, neutropenia, and thrombocytopenia were observed in one patient (2.8%) each.Weekly carboplatin and concurrent radiation therapy was safe in older adults with locally advanced NSCLC, and promising activity was observed. [ABSTRACT FROM AUTHOR]

Glioneuronal and neuronal tumors (GNTs) are slow‐growing, lower‐grade neuroepithelial tumors characterized by mature neuronal differentiation and, less consistently, glial differentiation. Their identification has traditionally relied on histological proof of neuronal differentiation, reflecting the well‐differentiated nature of GNTs. However, after discovering genetic alterations in GNTs, particularly those in the MAP‐kinase pathway, it became evident that histological diagnoses do not always correlate with genetic alterations and vice versa. Therefore, molecular‐based classification is now warranted since several inhibitors targeting the MAP‐kinase pathway are available. The World Health Organization classification published in 2021 applied DNA methylation profiling to segregate low‐grade neuroepithelial tumors. As GNTs are essentially indolent, radical resection and unnecessary chemoradiotherapy may be more harmful than beneficial for patients. Preserving tumor tissue for potential future treatments is more important for patients with GNTs. [ABSTRACT FROM AUTHOR]

Pancreatic adenocarcinoma is a growing cause of cancer mortality. Most cases are diagnosed late, with only around 20% of tumors being resectable, borderline or locally advanced and potentially resectable. Tumors are classically classified according to anatomical criteria. Since 2019, however, biological and clinical criteria have been added (A, B and C classification). Neoadjuvant treatment, based essentially on chemotherapy including FOLFIRINOX, aims to improve the chances of complete resection (R0), to treat micrometastases early and to better select the patients for surgery. Nevertheless, despite this rationale, and the evolution of practices towards "all neoadjuvant", it does not seem so clear that this strategy is the best for upfront resectable tumors. In this update, we report on the latest available data on the evaluation of the benefit of neoadjuvant treatment. The definition of tumor resectability will be reviewed, along with the different treatment modalities (type of chemotherapy, radiotherapy, chemoradiotherapy). [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusions One‐third of head and neck squamous cell carcinomas are early‐stage oral cavity squamous cell carcinomas (OCSCC). Despite a high curative rate, 20% of early‐stage OCSCC patients do not achieve long‐term survival. This study evaluates the role of adjuvant therapy (ADJ) in delaying disease progression and prolonging survival.This single‐institute retrospective cohort study enrolled 481 early‐stage OCSCC patients, 16% (78/481) of whom received ADJ. It was reported according to the STROBE guidelines. Cox proportional hazards regression and Kaplan–Meier survival curves were employed to identify suitable candidates for ADJ.The 5‐year locoregional recurrence‐free survival (LR‐RFS) and overall survival rates were 73.2% and 84.9%, respectively. Positive margins and advanced depth of invasion (DOI) were independent predictors of LR‐RFS. For patients with positive margins, adjuvant chemoradiotherapy (CRT) was superior to adjuvant radiotherapy alone in improving LR‐RFS (hazard ratios for adjuvant CRT vs. none, 0.042; adjuvant radiotherapy alone vs. none, 0.702). Excluding positive margins, advanced DOI was the most critical factor in assessing the need for ADJ. Positive margins and advanced DOI were more appropriate criteria than EORTC 22931/RTOG 9501 for evaluating adjuvant CRT.Adjuvant CRT was indicated for patients with positive margins and advanced DOI to improve survival outcomes. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemoradiotherapy (nCRT) followed by surgery remains a standard of care for resectable esophageal cancer (EC), and definitive chemoradiotherapy (dCRT) is an alternative for unresectable diseases. However, it is controversial for the use of the two aggressive regimens in elderly patients. Methods: We systematically searched multiple databases for studies comparing overall survival (OS) and/or progression-free survival (PFS) between dCRT and surgery (nCRT + surgery or surgery alone) or between dCRT and radiotherapy (RT) alone in elderly patients (age ≥ 65 years) until March 28, 2024. Statistical analysis was performed using random-effects model. Results: Fourty-five studies with 33,729 patients were included. dCRT significantly prolonged OS (hazard ratio [HR] = 0.64, 95% confidence interval [CI]: 0.58–0.70) and PFS (HR = 0.67, 95% CI: 0.60–0.76) compared to RT alone for unresectable EC, and resulted in a worse OS compared to surgery for resectable cases (HR = 1.34, 95% CI: 1.23–1.45). Similar results of OS were also observed when the multivariate-adjusted HRs were used as the measure of effect (dCRT vs. RT alone: HR = 0.65, 95% CI: 0.58–0.73; dCRT vs. surgery: HR = 1.49, 95% CI: 1.28–1.74). Subgroup analyses according to age group (≥ 70, ≥ 75, or ≥ 80 years), study design, study region, histological type, radiation field, chemotherapy regimen revealed comparable results. Conclusions: nCRT + surgery is likely a preferred strategy for elderly patients with good physiological conditions; and dCRT is a better alternative for unresectable cases. Advanced age alone does not appear to be a key predictor for the tolerability of the two aggressive treatments. [ABSTRACT FROM AUTHOR]