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Purpose This study aimed to identify patients who would benefit from third and subsequent lines of chemotherapy in recurrent epithelial ovarian cancer (EOC).Materials and Methods Recurrent EOC patients who received third, fourth, or fifth-line palliative chemotherapy were retrospectively analyzed. Patients’ survival outcomes were assessed according to chemotherapy lines. Based on the best objective response, patients were divided into good-response (stable disease or better) and poor response (progressive disease or those who died before response assessment) groups. Survival outcomes were compared between the two groups, and factors associated with chemotherapy responses were investigated.Results A total of 189 patients were evaluated. Ninety-four and 95 patients were identified as good and poor response group respectively, during the study period of 2008 to 2021. The poor response group showed significantly worse progression-free survival (median, 2.1 months vs. 9.7 months; p < 0.001) and overall survival (median, 5.0 months vs. 22.9 months; p < 0.001) compared with the good response group. In multivariate analysis adjusting for clinicopathologic factors, short treatment-free interval (TFI) (hazard ratio [HR], 5.557; 95% confidence interval [CI], 2.403 to 12.850), platinum-resistant EOC (HR, 2.367; 95% CI, 1.017 to 5.510), and non-serous/endometrioid histologic type (HR, 5.045; 95% CI, 1.152 to 22.088) were identified as independent risk factors for poor response. There was no difference in serious adverse events between good and poor response groups (p=0.167).Conclusion Third and subsequent lines of chemotherapy could be carefully considered for palliative purposes in recurrent EOC patients with serous or endometrioid histology, initial platinum sensitivity, and long TFIs from the previous chemotherapy regimen.

Purpose Angiogenesis is a crucial phenomenon in the development and progression of breast cancer (BC), but the clinical significance of angiogenesis-related proteins in metastatic BC remains unknown. This study investigates the prognostic value of vascular endothelial growth factor receptors 1, 2, 3 (VEGFR1, VEGFR2, VEGFR3) as well as vascular endothelial growth factors A and C (VEGFA and VEGFC) in metastatic BC patients treated with trastuzumab-based regimens.Materials and Methods Two hundred female patients were included. Protein and mRNA expression of the studied angiogenesis-related factors were evaluated by immunohistochemistry and quantitative polymerase chain reaction, respectively.Results High expression of VEGFA, VEGFC, VEGFR1, VEGFR2, and VEGFR3 in the tumor cells was observed in 43.5%, 24.2%, 36%, 29.5%, and 43%, respectively. Stromal elements expressed high levels of VEGFA, VEGFC, VEGFR1, VEGFR2, and VEGFR3 in 78.9%, 93.3%, 90.7%, 90.2%, and 74.8% of tumors with available data. High tumor cell expression of VEGFR1 was a favorable prognosticator for survival among patients with human epidermal growth factor receptor 2 (HER2)–positive tumors (hazard ratio [HR], 0.55; p=0.013). A trend towards longer progression-free survival was detected univariately for patients with HER2-negative tumors and high expression of VEGFR2 (HR, 0.60; p=0.059).Conclusion VEGFR1 and VEGFR2 seem to have significant prognostic value in BC patients with metastatic disease treated with trastuzumab-based regimens.

Background With a 5% improvement in 5-year overall survival achieved with current neoadjuvant or adjuvant chemotherapy, new treatments for resectable non-small cell lung cancer (NSCLC) are urgently needed. The use of immune checkpoint inhibitors (ICIs) is established in metastatic NSCLC and is being evaluated in resectable NSCLC. Methods Publications and conference databases and clinicaltrials.gov were searched for reports on clinical studies of neoadjuvant immunotherapy in patients with early resectable NSCLC. Results Potential advantages of neoadjuvant ICIs include the following: earlier treatment of micrometastatic disease; activation of a broader, potentially durable immune response by the whole tumor and associated lymph nodes; and pathologic assessment of neoadjuvant treatment response, which may guide adjuvant therapy. Surgical considerations include delays to surgery, potential disease progression preventing curative resection, and perioperative morbidity and mortality. Surrogate end points of efficacy (pathologic complete response, major pathologic response) and biomarkers predictive of outcome (programmed death ligand 1 expression, tumor mutational burden, and circulating tumor DNA) can accelerate clinical trial completion and early-stage treatment development; their application in neoadjuvant ICI studies in NSCLC is reviewed. Conclusions Phase 2 trials of neoadjuvant ICIs alone or in combination with chemotherapy showed encouraging safety and efficacy in patients with resectable NSCLC, thus warranting the ongoing phase 3 studies of neoadjuvant immunotherapy combined with chemotherapy. Preoperative and intraoperative unresectability after neoadjuvant ICIs appears comparable to that observed with neoadjuvant chemotherapy. To help thoracic surgeons and medical oncologists to distinguish among ICIs beyond efficacy as phase 3 data emerge, surgery-related end points for perioperative morbidity, mortality, and complexity should be defined, standardized, incorporated into trial designs, and reported.

BackgroundRenal cell carcinoma (RCC) comprises of a spectrum of clinico-pathologically distinct entities thereby making it difficult to accurately predict the clinical outcome. Though many predictive factors have been described in literature, tumor stage and nuclear grade have been established to consistently correlate with the tumor behaviour. However, tumors in the same stage have shown to behave differently. Similarly subjectivity and lack of reproducibility in nuclear grade mandates use of more objective parameters such as digital nuclear morphometry which could provide consistent and more reliable results in predicting prognosis. The study was conducted with the main objective of comparing the histological grade and the nuclear morphometric variables in RCC for predicting the clinical outcome.Material and methodsA total of 219 cases of renal tumors in adults were retrieved retrospectively from the archives of pathology department in Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow and their clinical, gross and microscopic features were noted. Nuclear grading was done in 181 cases of clear cell and papillary RCC of which computer-assisted morphometry for various nuclear parameters was done in 100 cases where a follow-up data of at least 3 years was available. Nuclear grade and morphometric parameters were correlated statistically with the clinical outcome of the patients.ResultsHistological nuclear grade did not show statistically significant correlation with progression free survival (PFS). Higher values of mean nuclear area, mean nuclear circumference, mean nuclear major diameter and mean nuclear minor diameter were significant predictors of PFS with a strong inverse correlation.ConclusionNuclear morphometry is a more reliable predictor of clinical outcome in patients of RCC when compared to histological grade and should be included in predictive model with other clinical and pathological parameters to accurately determine tumor behaviour.

Trimodality therapy using the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) trial protocol is an accepted standard of care for locally advanced oesophageal and gastroesophageal junction cancers. For medically inoperable patients, chemoradiotherapy (CRT) has been a therapeutic option.This single institution review aimed to assess the real-world application of the CROSS trial protocol.This is a retrospective review of 83 patients who underwent CRT with carboplatin and paclitaxel with trimodality or definitive intent between June 2012 and June 2018. Sixty-five patients underwent neoadjuvant CRT (NCRT); 40 had surgery, 18 had definitive CRT (DCRT). Patients' demographics, clinical, pathological, treatment and surgical characteristics were assessed. The data were analysed in exploratory analyses and Kaplan-Meier curves.For 83 patients, the following median values were seen: radiotherapy dose, 50.4 Gy; chemotherapy doses, 5; and time from CRT to surgery, 62 days. Twenty-three percent NCRT and 72% DCRT patients were aged ≥75 years, and 49% and 33% of these respectively had no interruptions to CRT. Patients aged ≥75 years were more likely to have DCRT (P = 0.001). Patients who underwent surgery were younger (P = 0.04). For NCRT and surgery, NCRT only and DCRT respectively, median overall survival was 35.5, 12.1 and 17.1 months (log rank P = 0.008); progression-free survival was 32.2, 10 and 9.6 months (log rank P = 0.001).Despite broadening of the CROSS trial eligibility criteria in our real-world data, there appears to be a survival benefit with trimodality therapy. The use of carboplatin and paclitaxel in DCRT may be of value and requires further study.

The clinicoprognostic implications of head and neck involvement of mycosis fungoides (MF) are poorly understood.To evaluate the association of head and neck involvement on the clinicoprognostic features of MF.The clinical features and survival outcomes of patients with MF in a Korean academic medical center database were retrospectively evaluated according to the presence of head and neck involvement at diagnosis.Cases of MF with (group A, n = 39) and without (group B, n = 85) head and neck involvement at diagnosis were identified. Advanced-stage disease (stages IIB-IVB) was more common in group A (43.6%) than in group B (5.9%) (P .001). MF progression, extracutaneous dissemination, and large-cell transformation more commonly occurred in group A than in group B. The 10-year overall survival rate was worse in group A (53.4%) compared with group B (81.6%) (P .001). Head and neck involvement at diagnosis was associated with poor prognosis in early-stage MF (stages IA-IIA) and was independently associated with worse progression-free survival (hazard ratio, 24.4; 95% confidence interval, 2.2-267.6; P = .009).A single center, retrospective design.Head and neck involvement of MF was associated with a poor prognosis.

This translational study aims to investigate the clinical benefits of indocyanine green (ICG) based near-infrared window II (NIR-II) fluorescence image-guided surgery (FGS) on high-grade glioma (HGG) patients.Patients were randomly assigned to receive FGS or traditional white light image-guided surgery (WLS). The detection rate of NIR-II fluorescence was observed. Complete resection rate, progression-free survival (PFS), overall survival (OS), and neurological status were compared. Tissue samples were obtained from the FGS group, with the diagnosis based on the surgeons and the fluorescence recorded for comparison of diagnostic capability. Patients with WHO grade III gliomas or glioblastomas (GBM) were analyzed separately.15 GBM and 4 WHO grade III glioma patients in the FGS group and 18 GBM and 4 WHO grade III glioma patients in the WLS group were enrolled. The detection rate of NIR-II fluorescence was 100% for GBM. The complete resection rate was significantly increased by the FGS for GBM (FGS, 100% [95% CI 73.41-100] vs. WLS, 50% [95% CI 29.03-70.97], P = 0.0036). The PFS and OS of the FGS group were also significantly prolonged (Median PFS: FGS, 9.0 months vs. WLS, 7.0 months, P0.0001; Median OS: FGS, 19.0 months vs. WLS, 15.5 months, P = 0.0002). No recurrence was observed in WHO grade III glioma patients.NIR-II FGS achieves a much better complete resection rate of GBM than conventional WLS, leading to greatly improved survival of GBM patients.NIR-II FGS is a highly promising technique worthy of exploring more clinical applications.

BACKGROUND CONTEXT With improvements in adjuvant radiotherapy and minimally invasive surgical techniques, separation surgery has become the default surgical intervention for spine metastases at many centers. However, it is unclear if there is clinical benefit from anterior column resection in addition to simple epidural debulking prior to stereotactic body radiotherapy (SBRT). PURPOSE To examine the effect of anterior column debulking versus epidural disease resection alone in the local control of metastases to the bony spine. STUDY DESIGN Retrospective cohort study. PATIENT SAMPLE Ninety-seven patients who underwent open surgery followed by SBRT for spinal metastases at a single comprehensive cancer center. OUTCOME MEASURES Local tumor recurrence following surgery and SBRT. METHODS Data were collected regarding radiation dose, cancer histology, extent of anterior column resection, and recurrence. Tumor involvement was categorized using the International Spine Radiosurgery Consortium guidelines. Univariable analyses were conducted to determine predictors of local recurrence and time to local recurrence. RESULTS Among the 97 included patients, mean age was 60.5±11.4 years and 51% of patients were male. The most common primary tumor types were lung (20.6%), breast (17.5%), kidney (13.4%) and prostate (12.4%). Recurrence was seen in 17 patients (17.5%) and local control rates were: 85.5% (1-year), 81.1% (2-year), and 54.9% (5-year). Overall predictors of local recurrence were tumor pathology (p

Aim: To assess relations between Valsalva- and phenylephrine test-derived measures and outcome in reduced ejection fraction heart failure (HFrEF) patients receiving comprehensive neurohormonal blockade pharmacotherapy. Methods: Data from 56 HFrEF patients (LVEF: 32±6%; mean±SD) subjected to Valsalva and phenylephrine tests were analyzed retrospectively. Baroreflex-related (Valsalva-ratio [cBRSVR] and BP-RRI slope from phase IV [cBRSIV_SLOPE]) and non-baroreflex-related measures (systolic BP rise in phase IV [ΔSBPPHASE_IV], and pulse-amplitude-ratio [PAR]) were calculated from Valsalva. Short-term outcome (HF-related hospitalization, ICD shock or all-cause death within 24-months from examination) and long-term outcome (ICD shock or all-cause death within 60-months) were analyzed. Results: The endpoint occurred in 16 and 18 patients, for short- and long-term outcome, respectively. Low ΔSBPPHASE_IV identified patients at risk in long-term perspective, as evidenced by low- vs. high ΔSBPPHASE_IV comparison (square-wave response patients assigned to low ΔSBPPHASE_IV group, P=0.002), and Cox model (HR: 0.91, CI: 0.86-0.96, P Conclusions: Non-baroreflex-related measures obtained from Valsalva: ΔSBPPHASE_IV and PAR, might carry prognostic value in HFrEF patients receiving neurohormonal blockade pharmacotherapy.

Purpose This study aimed to investigate the impact of postoperative radiotherapy (PORT) in de novo metastatic breast cancer (dnMBC) patients undergoing planned primary tumor resection (PTR) and to identify the subgroup of patients who would most benefit from PORT.Materials and Methods This study enrolled 426 patients with dnMBC administered PTR alone or with PORT. The primary and secondary outcomes were overall and progression-free survival (OS and PFS), respectively.Results The median follow-up time was 53.7 months (range, 3.1 to 194.4). The 5-year OS and PFS rates were 73.2% and 32.0%, respectively. For OS, clinical T3/4 category, triple-negative breast cancer (TNBC), postoperative chemotherapy alone were significantly poor prognostic factors, and administration of PORT failed to show its significance. Regarding PFS, PORT was a favorable prognostic factor (hazard ratio, 0.64; 95% confidence interval, 0.50 to 0.82; p < 0.001), in addition to T1/2 category, ≤ 5 metastases, and non-TNBC. According to the multivariate analyses of OS in the PORT group, we divided the patients into three groups (group 1, T1/2 and non-TNBC [n=193]; group 2, T3/4 and non-TNBC [n=171]; and group 3, TNBC [n=49]), and evaluated the effect of PORT. Although PORT had no significance for OS in all subgroups, it was a significant factor for good prognosis regarding PFS in groups 1 and 2, not in group 3.Conclusion PORT was associated with a significantly better PFS in patients with dnMBC who underwent PTR. Patients with clinical T1/2 category and non-TNBC benefited most from PORT, while those with TNBC showed little benefit.

To review surgical management, tumour stage and clinical outcomes in children with intravascular extension of Wilms tumour (WT) registered in a national clinical study (2012-19).WTs with presence/suspicion of tumour thrombus in the renal vein (RV) or beyond on radiology, surgery or pathology case report forms were identified. Only cases where thrombus was confirmed by surgeon and/or reference pathologist were included. Surgical management, disease stage, overall (OS) and event free survival (EFS) were investigated.69/583 (11.8%) patients met the inclusion criteria. Forty-six (67%) had abdominal stage III due to thrombus-related reasons: 11 had macroscopically incomplete resection, including 8 cases where cavotomy was not performed; 20 had piecemeal complete resection of thrombus; 15 had microscopically positive resection margins at the RV. 66% of tumour thrombi contained viable tumour. There were eight relapses and five deaths. EFS, but not OS, was significantly associated with completeness of surgical resection (P0.05). OS and EFS were also significantly associated with histological risk group (P0.05) but not with viability of tumour thrombus (P=0.19; P=0.59).WTs with intravascular extension have a high risk of local stage III due to thrombus-related reasons. Controlled complete removal of the thrombus should be the aim of surgery.Level II.

Early tumor size reduction (TSR) has been explored as a prognostic factor for survival in patients with advanced melanoma in clinical trials. The purpose of this analysis is to validate, in a routine clinical milieu, the predictive capacity of TSR by 10% for overall survival (OS) and progression-free survival (PFS) and to compare its predictive performance with the RECIST 1.1 criteria.This retrospective study was approved by the local ethics committee. A total of 152 patients with both CT before immunotherapy initiation and at first response evaluation after immunotherapy initiation were included. Prior to statistical analysis, treatment response was trichotomized as follows: Complete response and/or partial response, stable disease and progressive disease. Furthermore, response was dichotomized regarding TSR (TSR ≥ 10% and TSR10%). Kaplan-Meier survival estimates, Cox regression and Harrel's concordance index (C-index) were computed for prediction of overall survival and progression-free survival.Tumor size reduction by at least 10% significantly differentiated between patients with increased survival from the ones with decreased survival (median OS: TSR ≥ 10%: 2137 days vs. TSR10%: 263 days) (p0.001) (median PFS: TSR ≥ 10%: 590 days vs. TSR10%: 11 days) (p0.001). RECIST 1.1. criteria had a slightly higher C-index for overall survival reflecting a slight superior predictive capacity (RECIST: 0.69 vs TSR: 0.64) but a similar predictive capacity regarding progression-free survival (both: 0. 63).Early tumor size reduction serves as a simple-to-use metric which can be implemented on the first follow-up CT. Tumor size reduction by at least 10% can be considered an additional biomarker predictive of overall survival and progression-free survival in routine clinical care and not only in the context of clinical trials in patients with advanced melanoma undergoing immunotherapy. Nevertheless, RECIST-based criteria should remain the main tool of treatment response assessment until results of prospective studies validating the TSR method are available.

Stereotactic body radiation therapy (SBRT) has increasingly been used to treat early-stage primary lung cancers, but its effectiveness and safety in patients with multiple synchronous primary lung tumors is not as well established. Our aim was to evaluate clinical outcomes, patterns of recurrence, and toxicities for these patients.We queried an institutional database of patients treated with SBRT for primary lung tumors from 2007 to 2019. Patients with known metastatic disease were excluded. Recurrences were described as new primaries (NP) if they occurred as an isolated pulmonary mass outside the previous planning target volume.We analyzed 126 lesions from 60 consecutive patients who received SBRT synchronously to ≥2 lesions for nonmetastatic lung cancers. Median total dose per lesion was 50 Gy (range, 30-60 Gy) delivered over 3 to 5 fractions. All but 4 lesions were treated to a biologically effective dose ≥100 Gy. The median follow-up time was 47.3 months (interquartile range, 34.1-65.6). Median overall survival was 46.2 months. Two and 5-year overall survival for all patients was 70% and 48%, respectively. Median progression-free survival was 26 months (interquartile range, 7.6-32.6), and at the time of data collection 25 patients (42%) had experienced any disease progression. Median time to progression was 36 months: 9 (15%) patients experienced local failure, with 1- and 2-year local failure rates of 8% and 13%, respectively. Four patients (7%) experienced regional failure, at 3, 10, 30, and 50 months. Eleven patients (18%) experienced distant failure, with 2-year distant failure rate of 13%. Thirteen patients (21%) developed NPs, with 2-year NP rate of 15.1%. Fourteen patients (23%) experienced Common Terminology Criteria for Adverse Events grade ≥2 toxicity, and 2 patients (3%) experienced Common Terminology Criteria for Adverse Events grade ≥3 toxicity (pneumonitis and hemoptysis).Synchronous SBRT to biologically effective dose ≥100 Gy appears safe and effective for selected patients with synchronous primary lung tumors.

Background Although basal cell carcinoma (BCC) tends to follow an indolent course, some tumors can exhibit locally aggressive behavior and invade into bone. Objective To analyze all published demographic, clinical, and treatment data on recurrence patterns, disease progression, disease-specific death, and overall mortality of BCC with bone invasion. Methods A systematic review and pooled-survival analysis was performed, including case reports and case series of BCC with bone invasion. Results The study included 101 patients from 70 publications. BCC tumors invading into bone were most often large, neglected tumors located in high-risk face areas. At 5 years, patients had a 30% risk probability of disease recurrence (after negative margins), a 72.1% risk of disease progression or death (with ambiguous margin status), an 18.2% risk of BCC-related death, and a 20.7% overall probability of death. Limitations Limitations include the reliance on case reports and series for individual patient data, which has the potential to introduce selection bias. Conclusion The high rate of disease progression and suboptimal 5-year survival rate highlights the poor prognosis of BCC with bone invasion and further underscores the importance of early detection and treatment.

Aim The aim of this study was to retrospectively analyze treatment outcomes and tolerance in patients in whom cabozantinib was used after previous targeted therapy. Patients and methods Cabozantinib was administered in dose 60 mg/day, a subset of patients received initial dose of 40 mg/day. The treatment was administered until to progression or unacceptable toxicity. CT scans were assessed according to the RECIST 1.1 and toxicity of treatment was assessed based on the CTCAE (version 4). Kaplan-Meier analysis was used to calculate progression free survival (PFS) and overall survival (OS). We performed a multivariate analysis of risk factors for treatment outcomes (PFS, OS) by Cox regression analysis. All statistics were evaluated at the significance level alpha = 0.05. Results 54 patients with metastatic renal cell carcinoma (mRCC) were evaluated. Median PFS in all patients treated with cabozantinib was 9.3 months (95% CI 5.3 - 13.3). One-year survival was 85.2% (95% CI 72.9 - 93.4%). Treatment response was observed in 45.9% of cases, including one complete remission. Cox regression analysis demonstrated that presence of subsequent treatment was the only factor with a significant effect on OS (P=0.008). Adverse events occurred in 88.9% of patients, grade 3 - 4 in 46.3%. Conclusion The analysis of our cohort of patients treated with cabozantinib in the second or higher lines of treatment showed that cabozantinib represents an effective and safe therapy and contributes to longer survival of our mRCC patients.

Several studies have suggested that patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) might benefit from the use of tyrosine kinase inhibitors (TKIs) in combination with antiangiogenic agents. This study aimed to comprehensively review the available evidence regarding the efficacy and safety of first-line TKI plus antiangiogenic agents versus TKIs alone in EGFR-mutated advanced NSCLC.A literature search was performed using PubMed to identify studies published up to Feb. 2020. Abstracts from major international conferences reported over the last 5 years were searched. The primary outcome was progression-free survival (PFS), and the secondary outcomes included overall survival (OS), the objective response rate (ORR), and toxicity.In total, 7 relevant trials comprising 1612 patients were identified. TKIs plus antiangiogenic agents led to significant improvements in PFS regardless of the EGFR mutation subtype and presence of brain metastasis. In particular, in the subgroup with the L858R mutation, the hazard ratio (HR) of PFS was 0.58 (95% confidence interval [CI], 0.48-0.71, P.001). The OS following combined treatment was similar to that following TKI monotherapy. The ORR was increased with the use of TKIs plus antiangiogenic agents (HR 1.10, 95% CI, 1.01-1.20, P = .029). In the safety analyses, TKIs plus antiangiogenic agents exhibited a significantly increased incidence of adverse events of grade 3 or higher.The use of TKIs plus antiangiogenic agents is associated with significantly improved PFS and ORR compared with TKIs alone in untreated EGFR-mutated NSCLC. The toxicities of combination therapy should be considered when making treatment choices.

Background and aim Whereas Yttrium-90 selective internal radiation therapy (Y-90 SIRT) was shown to improve local tumor control in non-Asian population, the efficacy of this therapy for Asian population in real-world setting remains poorly detailed. We aimed to determine outcomes and identify predictors of response in hepatocellular carcinoma (HCC) patients treated by Y-90 SIRT. Methods We retrospectively enrolled 52 HCC patients receiving Y-90 SIRT at our tertiary center between 2014 and 2019. Overall survival (OS), progression free survival (PFS), and predictive factors were determined by Kaplan–Meier method and Cox-proportional hazard analysis. Results Of the 52 patients (81% male, mean age 64.9 years), 71% and 29% were classified as Barcelona Clinic Liver Cancer stage C and B HCC, respectively; 63% had portal vein thrombosis, and 35% had objective tumor response defined by the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. OS and PFS were 11.0 and 2.4 months, respectively. Two patients were successfully down-staged and further underwent surgical resection. Multifocal lesion, alpha-fetoprotein (AFP) ≥200 ng/mL, and Eastern Cooperative Oncology Group (ECOG) score ≥1 were significantly associated with poor survival, with adjusted hazard ratio (95% confidence interval) of 7.7 (2.0–29.8), 5.4 (2.0–14.7), and 3.1 (1.0–9.6), respectively (all in P Conclusions Y-90 SIRT is an effective treatment for the local tumor control of HCC without serious adverse events. Single lesion, AFP level and ECOG status were predictors of response.

Introduction After high dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT), in patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL) and Hodgkin lymphoma (HL), involved field radiation therapy (RT) for consolidation and residual/progressive disease (PD) eradication is a common practice. Materials and methods Retrospective single-institution cohort analysis to evaluate the impact of early RT after HDC auto-SCT. Results Between 1996 and October 2019, 153 patients (43 DLBCL, 110 HL) underwent RT after HDC auto-SCT. Males 95 (62%), females 58 (38%), median age 24 years. Indications for RT was consolidation 65%: residual disease eradication 16%: and PD eradication 19%. For DLBCL, the median overall survival (OS) for the above indications was not reached (NR):NR:2 months and the KM 5-year OS was 72.6%:64.3%:12.5% respectively (P ≤ .000). Pair-wise analysis showed that consolidation versus residual disease eradication had no difference (P = .88) but both were superior to PD disease eradication (P ≤ 000 and P = .005 respectively). For HL, indication for RT was, 54%:23%:24% respectively. The median OS was NR:NR:28.8 months and KM 5-year OS was 82.3%:78%:30% respectively (P ≤ .000). Pair-wise analysis showed that consolidation versus residual disease eradication had no difference (P = .98) but both were superior to the PD eradication group (P ≤ 000). RT was well tolerated with no significant long-term toxicity. Conclusion Post HDC auto-SCT RT was well tolerated. DLBCL and HL patients with residual disease treated with the RT had similar long-term survival as those who received RT for consolidation. RT failed to improve the poor survival in patients with post-HDC auto-SCT PD.

Purpose/Objective(s) To develop a comprehensive framework to simulate the response to immune checkpoint inhibitors (ICIs) in combination with radiotherapy (RT) and to apply the framework for investigating ICI-RT combination regimen in hepatocellular carcinoma (HCC) patients. Materials/Methods The mechanistic mathematical model is based on dynamic biological interactions between the immune system and the tumor using input data from patient blood samples and outcomes of clinical trials. The cell compartments are described by ordinary differential equations and represent irradiated and non-irradiated tumor cells and lymphocytes. The effect of ICI is modeled using an immune activation term that is based on tumor size changes observed in a phase 1/2 clinical trial for HCC. Simulated combination regimen are based on ongoing ICI-RT trials. Results The proposed framework successfully describes tumor volume trajectories observed in early-stage clinical trials of durvalumab monotherapy in HCC patients. For ICI-RT treatment regimen the irradiated tumor fraction is the most important parameter for the efficacy. For 90% of the tumor cells being irradiated, adding RT to ICI yields an increase in clinical benefit from 33% to 71% in non-irradiated tumor sites. The model agrees with clinical data showing an association of outcome with initial tumor volume and lymphocyte counts. We demonstrate model application in clinical trial design to predict progression-free survival curves, showing that the cohort size to show significant improvement heavily depends on the irradiated tumor fraction. Conclusion We present a framework extending radiation cell kill models to include circulating lymphocytes and the effect of ICIs and enable simulation of combination strategies. The simulations predict that a significant amount of the benefit from RT in combination with ICI stems from the reduction in irradiated tumor burden and associated immune suppression. This aspect needs to be included in the interpretation of outcomes and the design of novel combination trials.

Objective The role of alternate sequential administration of sunitinib and capecitabine/temozolomide (CAPTEM) in metastatic pancreatic neuroendocrine tumors (PanNETs) remains unexplored. We thus aimed to analyze the efficacy and tolerability of this strategy in advanced grade 1/grade 2 PanNETs. Methods In total, data of 43 patients with metastatic PanNET were collected from a real-world database of a cancer center. Twenty-four patients were treated with sunitinib followed by CAPTEM (group 1), and 19 patients were treated with CAPTEM followed by sunitinib (group 2). Results Twenty-three patients were treated with first-line sunitinib or CAPTEM, and 20 patients were pretreated with somatostatin analog (SSA) or SSA in combination with transcatheter arterial chemoembolization. The objective response rate with first-line treatment was similar in both groups, whereas that with second-line treatment was higher in group 1 than in group 2, albeit with no significant differences (21.1% vs 5.3%, respectively; P = .205). Median progression-free survival (mPFS) for first-line and second-line treatments did not differ between the 2 groups (11 and 12 months vs 12 and 8 months, respectively). Following subgroup analyses, treatment with first-line sunitinib and sunitinib after pretreated SSA had a longer mPFS than that with second-line sunitinib after CAPTEM (11 months vs 8 months, respectively; P = .046), whereas treatment with first-line CAPTEM and CAPTEM after pretreated SSA had an mPFS similar to that of second-line CAPTEM after sunitinib treatment. CAPTEM and sunitinib had similar tolerability. Conclusion Alternating sunitinib and CAPTEM were well tolerated and associated with similar mPFS in grade 1/grade 2 PanNETs. However, larger prospective studies are required to investigate the efficacy of alternate sequential therapies for metastatic PanNET.

Randomized clinical trials have shown that regional nodal irradiation (RNI) in patients with unselected N1 breast cancer improves breast cancer-specific survival. However, the benefit of RNI in women with biologically low-risk N1 breast cancer is uncertain. We conducted a population-based study to determine whether RNI is associated with improved breast cancer recurrence-free interval (BCRFI) in this population.Patients aged 40 to 79 years with pT1-2 pN1 (node-positive) breast cancer diagnosed between 2005 and 2014 were identified. The inclusion criteria were modeled off of the TAILOR RT study, which is a randomized noninferiority clinical trial designed to assess the value of RNI in patients with low-risk N1 disease. Eligible patients had breast-conserving surgery or mastectomy and axillary lymph node dissection with 1 to 3 positive nodes, breast-conserving surgery and sentinel lymph node biopsy with 1 to 2 positive nodes, or mastectomy and sentinel lymph node biopsy with 1 positive node. Additionally, patients had luminal A breast cancers, as approximated by estrogen receptor positive (Allred 6-8/8), progesterone receptor (PR) positive (Allred 6-8/8), human epidermal growth factor receptor 2-negative, and grade 1 to 2 immunohistochemical testing. All patients were prescribed hormonal treatment. The primary endpoint of BCRFI, the time to any breast cancer recurrence or breast cancer-related death, was analyzed using a multivariate competing risks analysis.The cohort included 1169 women with a median follow-up of 9.2 years. Radiation treatments were not performed in 151 women treated with mastectomy alone, were delivered to the breast only in 133 women, and were delivered locoregionally in 885 women. Patients undergoing RNI were younger (median age: 58 vs 62 years), more likely to have 2 to 3 macroscopic lymph nodes involved, and more often received chemotherapy (all P.05). The 10-year estimate of BCRFI was 90% without RNI versus 90% with RNI (P = .5). On multivariable analysis, RNI was not a significant predictor of BCRFI (hazard ratio: 1.0; P = .9).In this retrospective analysis, RNI was not associated with improved BCRFI for women with biologically low-risk N1 breast cancer. We advocate accrual to the ongoing TAILOR RT study.

Laparoscopic surgery for transverse colon cancer has been excluded from 7 randomized trials for various reasons. The optimal procedure for transverse colon cancer remains controversial.This study aimed to analyze the patterns of lymph node metastasis in transverse colon cancer and to report short- and long-term outcomes of the treatment procedures.This was a single-center retrospective study.This study was conducted at Cancer Institute Hospital, Tokyo, Japan.We enrolled 252 patients who underwent laparoscopic surgery for transverse colon cancer.The transverse colon was divided into 3 segments, and the procedures for transverse colon cancer were based on these segments, as follows: right hemicolectomy, transverse colectomy, and left hemicolectomy.Postoperatively, the surgeons identified and mapped the lymph nodes from specimens and performed formalin fixation separately to compare the results of the pathological findings.For right-sided, middle-segment, and left-sided transverse colon cancers, the frequency of lymph node metastases was 28.2%, 19.2%, and 19.2%. Skipped lymph node metastasis occurred in right-sided and left-sided transverse colon cancers but not in middle-segment transverse colon cancers. The pathological vascular invasion rate was significantly higher in right and left hemicolectomy than in transverse colectomy. For right hemicolectomy, transverse colectomy, and left hemicolectomy, 5-year overall survival rates were 96.3%, 92.7%, and 93.7%, and relapse-free survival rates were 92.4%, 88.3%, and 95.5%. In multivariate analysis, the independent risk factor for relapse-free survival was lymph node metastasis.Selection bias and different backgrounds may have influenced surgical and long-term outcomes.Laparoscopic surgery for transverse colon cancer may be a feasible technique. Harvested lymph node mapping after laparoscopic resection based on D3 lymphadenectomy may help guide the field of dissection when managing patients who have transverse colon cancer. The only independent prognostic factor for relapse-free survival was node-positive cancer. See Video Abstract at http://links.lww.com/DCR/B706.MAPEO DE GANGLIOS LINFÁTICOS EN CÁNCER DE COLON TRANSVERSO TRATADO MEDIANTE COLECTOMÍA LAPAROSCÓPICA CON LINFADENECTOMÍA D3ANTECEDENTES:La cirugía laparoscópica en casos de cáncer de colon transverso fué excluida de siete estudios randomizados mayores por diversas razones. El procedimiento más idóneo en casos de cáncer de colon transverso, sigue siendo controvertido.OBJETIVO:Analizar los patrones de las metástasis en los ganglios linfáticos en casos de cáncer de colon transverso y reportar los resultados a corto y largo plazo de los diferentes procedimientos para su tratamiento.DISEÑO:Estudio retrospectivo en un solo centro de referencia.AJUSTE:Estudio llevado a cabo en el Hospital del Instituto del Cancer, Tokio, Japón.PACIENTES:Fueron incluidos 252 pacientes, sometidos a cirugía laparoscópica por cáncer de colon transverso.INTERVENCIONES:El colon transverso fué dividido en tres segmentos y los procedimientos en casos de cáncer se basaron sobre estos segmentos del tranverso, de la siguiente manera: hemicolectomía derecha, colectomía transversa y hemicolectomía izquierda.PRINCIPALES MEDIDAS DE RESULTADO:En el postoperatorio, los cirujanos identificaron y mapearon los ganglios linfáticos de las piezas quirúrgicas y las fijaron con formaldehido por separado para así poder comparar los resultados con los hallazgos histopatológicos.RESULTADOS:En los cánceres de colon transverso del segmento derecho, del segmento medio y del segmento izquierdo, la frecuencia de metástasis en los ganglios linfáticos fue del 28,2%, 19,2% y 19,2%, respectivamente. Las metástasis en los ganglios linfáticos omitidos se produjo en los cánceres de colon transverso del lado derecho y del lado izquierdo, pero no en los cánceres de colon transverso del segmento medio. La tasa de invasión vascular patológica fue significativamente mayor en la hemicolectomía derecha e izquierda que en la colectomía transversa. Para la hemicolectomía derecha, colectomía transversa y hemicolectomía izquierda, las tasas de supervivencia general a cinco años fueron del 96,3%, 92,7% y 93,7%, y las tasas de supervivencia sin recaída fueron del 92,4%, 88,3% y 95,5%, respectivamente. En el análisis multivariado, el factor de riesgo independiente para la sobrevida sin recidiva fue la metástasis en los ganglios linfáticos.LIMITACIONES:El sesgo de selección y los diferentes antecedentes pueden haber influido en los resultados quirúrgicos a largo plazo.CONCLUSIONES:La cirugía laparoscópica en casos de cáncer de colon transverso puede ser una técnica factible. El mapeo de los ganglios linfáticos recolectados después de la resección laparoscópica basada en la linfadenectomía D3 puede ayudar a guiar el campo de la disección en el manejo de pacientes con cáncer de colon transverso. El único factor pronóstico independiente para el SLR fue el cáncer con ganglios positivos. Consulte Video Resumen en http://links.lww.com/DCR/B706. (Traducción-Dr. Xavier Delgadillo).

The current American Joint Committee on Cancer tumor, lymph node, metastasis cancer staging system for papillary thyroid carcinoma places low weight on extranodal extension. This study examined the prognostic implications of extranodal extension in papillary thyroid carcinoma patients and attempted to design a new staging system incorporating extranodal extension.We reviewed data from 6,165 consecutive papillary thyroid carcinoma patients from 2012 to 2018. Patients with extrathyroidal extension or extranodal extension were included and then divided into 3 groups: extrathyroidal extension (papillary thyroid carcinoma with extrathyroidal extension but without extranodal extension, N = 457); extranodal extension (papillary thyroid carcinoma with extranodal extension but without extrathyroidal extension, N = 116); and extrathyroidal extension and extranodal extension (papillary thyroid carcinoma with both extrathyroidal extension and extranodal extension, N = 116). Recurrence-free survival and cancer-specific survival were compared before and after adjusting for differences using propensity score matching owing to observed heterogeneity in baseline characteristics in the original cohort. Recurrence-free survival and cancer-specific survival were also compared between patients with and without extranodal extension after matching at a 1:1 ratio. Cox proportional hazards regression analyses were used to identify the relationships of factors associated with structural recurrent disease in the node-positive subset. Then a new staging system incorporating extranodal extension was established, and the discrimination of the new staging system for recurrence-free survival and cancer-specific survival was investigated.Of the 6,165 patients with papillary thyroid carcinoma, extrathyroidal extension was found in 573 (9.3%) patients, and extranodal extension was observed in 232 (3.8%) patients. The recurrence-free survival and cancer-specific survival rates of patients with extranodal extension were similar to those of patients with extrathyroidal extension (all P.05). Patients with extrathyroidal extension and extranodal extension experienced worse recurrence-free survival than patients with extrathyroidal extension or extranodal extension and even worse cancer-specific survival than patients with extrathyroidal extension (all P.05). The recurrence-free survival and cancer-specific survival rates of patients with extranodal extension were worse than those of patients without extranodal extension (P = .003; P = .048). Cox proportional hazards regression analysis demonstrated that after propensity score matching, extranodal extension (hazard ratio 1.911; 95% confidence interval 1.568-3.609; P.001) remained an independent predictor of structural recurrent disease in patients with node-positive papillary thyroid carcinoma. After incorporating extranodal extension into the current tumor, lymph node, metastasis classification, the new staging system presented a better discrimination for recurrence-free survival and cancer-specific survival for those with lymph node metastasis.Papillary thyroid carcinoma patients with extranodal extension present worse prognosis, and incorporating extranodal extension in tumor, lymph node, metastasis classification identifies poor-risk patients more accurately.

Objectives This study aimed to evaluate the cost-effectiveness, from a US commercial payer perspective, of cemiplimab versus other first-line treatments for advanced non-small cell lung cancer with programmed death-ligand 1 expression ≥50%. Methods A 30-year “partitioned survival” model was constructed. Overall survival and progression-free survival were estimated by applying time-varying hazard ratios from a network meta-analysis of randomized clinical trials. Overall survival and progression-free survival were estimated from EMPOWER-Lung 1 (cemiplimab monotherapy vs chemotherapy) and KEYNOTE-024 and KEYNOTE-042 (pembrolizumab monotherapy vs chemotherapy). Drug acquisition costs were based on published 2020 US list prices. A 3% discount rate was applied to life-years, quality-adjusted life-years (QALYs), and costs. A deterministic analysis was performed on the base case; 1-way sensitivity and probabilistic sensitivity analyses assessed model and parameter uncertainties. Results Cemiplimab was associated with increased time in the “preprogression” (13.08 vs 7.90 and 6.08 months) and “postprogression” (47.30 vs 29.49 and 14.78 months) health states versus pembrolizumab and chemotherapy, respectively. Compared with pembrolizumab and chemotherapy, cemiplimab generated 1.00 (95% CI −0.266 to 2.440) and 1.78 (95% CI 0.607-3.20) incremental QALYs, respectively, with incremental cost-effectiveness ratios of $68 254 and $89 219 per QALY for cemiplimab versus pembrolizumab and cemiplimab versus chemotherapy, respectively. The probability of cemiplimab being cost-effective at a willingness-to-pay threshold of $100 000 to $150 000 per QALY was 62% to 76% versus pembrolizumab and 56% to 84% versus chemotherapy. Conclusions Findings suggest that cemiplimab, versus pembrolizumab or versus chemotherapy, is a cost-effective first-line treatment option for advanced non-small cell lung cancer with programmed death-ligand 1 expression ≥50%.

BACKGROUND: Circulating tumour cells (CTCs) can be used to monitor cancer longitudinally, but their use in non-small cell lung cancer (NSCLC) is limited due to low numbers in the peripheral blood. Through diagnostic leukapheresis (DLA) CTCs can be obtained from larger blood volumes.METHODS: Patients with all stages of NSCLC were selected. One total body blood volume was screened by DLA before and after treatment. Peripheral blood was drawn pre- and post DLA for CTC enumeration by CellSearch. CTCs were detected in the DLA product (volume equalling 2 × 108 leucocytes) and after leucocyte depletion (RosetteSep, 9 mL DLA product). Single-cell, whole-genome sequencing was performed on isolated CTCs.RESULTS: Fifty-six patients were included. Before treatment, CTCs were more often detected in DLA (32/55, 58%) than in the peripheral blood (pre-DLA: 18/55, 33%; post DLA: 13/55, 23%, both at p CONCLUSIONS: DLA detected nine times more CTCs than in the peripheral blood. The sustained presence of CTCs in DLA after treatment was associated with therapy failure and shortened PFS.TRIAL REGISTRATION: The study was approved by the Medical Ethical Committee (NL55754.042.15) and was registered in the Dutch trial register (NL5423).

Background Vestibular schwannoma (VS) is the most common tumour of the cerebellopontine angle. Owing to complex anatomy and high rates of morbidity, surgical management of large tumours is challenging. We seek to explore the clinical landscape of VS to identify predictors of outcome and help guide surgical decision making. Methods We retrospectively reviewed charts of patients who underwent primary surgery for VS between 2005 and 2020 at a quaternary referral center in Toronto, Canada. Mined data includes patient demographics, clinical presentation, radiological features, and treatment details. Regression modelling was used to identify predictors of tumour control, postoperative morbidity, and correlates of progression free survival (PFS). Results Two hundred and five tumours with sufficient data were included in our study. Syndromic NF2, large tumours (>3cm), subtotal resection (vs gross total resection), presence of edema on preoperative MRI, and preoperative trigeminal symptoms were all predictors of postoperative progression/need for further treatment; the latter four were also associated with shorter progression free survival. Extent of resection (EOR), tumour size, and Koos grade were independently predictive of postoperative progression/secondary intervention in multivariate models; however, only EOR was independently predictive of progression-free survival. EOR, tumour size, and patient age are each independently predictive of facial nerve outcome. Conclusions We comprehensively explore the clinical landscape of surgically treated vestibular schwannoma and highlight important outcome predictors and disease subgroups. This may have important implications in risk stratifying these challenging cases.

INTRODUCTION: This double-blind, parallel-group, active-controlled phase III trial (NCT02260804) assessed CT-P10 and rituximab safety and efficacy in patients with previously untreated low-tumor-burden follicular lymphoma (LTBFL), including after a single switch from rituximab to CT-P10. PATIENTS AND METHODS: LTBFL patients were randomized (1:1) to receive CT-P10 or rituximab (375 mg/m(2) intravenously; day 1 of 4 7-day cycles). Patients achieving disease control entered a 2-year maintenance period. CT-P10 or rituximab were administered every 8 weeks (6 cycles) in year 1; all patients could receive CT-P10 (every 8 weeks; 6 cycles) in year 2. Secondary endpoints (reported here) were overall response rate (ORR) during the study period, progression-free survival (PFS), time to progression (TTP), and overall survival (OS). Safety and immunogenicity were evaluated. RESULTS: Between November 9, 2015 and January 4, 2018, 258 patients were randomized (130 for CT-P10; 128 for rituximab). ORR was similar between groups over the study period (CT-P10: 88%; rituximab: 87%). After 29.2 months' median follow-up, median PFS, TTP, and OS were not estimable; 24-month Kaplan-Meier estimates suggested similarity between groups. Overall, 114 (CT-P10: 88%), and 104 (rituximab: 81%) patients experienced treatment-emergent adverse events. The single switch was well tolerated. CONCLUSION: These updated data support therapeutic similarity of CT-P10 and rituximab and support the use of CT-P10 monotherapy for previously untreated LTBFL.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the third leading cause of cancer-related death worldwide. Single-agent anti-PD-1 immune checkpoint inhibitors (ICIs) demonstrated promising efficacy in early-phase trials, a finding that was not confirmed in phase III studies. The combination of atezolizumab (an anti-PD-L1 ICI) with bevacizumab (an anti-VEGF antibody) was approved as first-line therapy in 2020, however, with significant improvement in response rate, progression-free survival, and overall survival in comparison with the previous standard of care, sorafenib. Numerous ongoing clinical trials are assessing ICIs in combination with each other or with targeted agents, and also in earlier stages with local therapies. This review summarizes the latest concepts in the use of ICIs for the management of HCC. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Background Human epidermal growth factor receptor 2 (HER2)-targeted therapies have not been approved for patients with non-small-cell lung cancer (NSCLC). The efficacy and safety of trastuzumab deruxtecan (formerly DS-8201), a HER2 antibody-drug conjugate, in patients with HER2-mutant NSCLC have not been investigated extensively. Methods We conducted a multicenter, international, phase 2 study in which trastuzumab deruxtecan (6.4 mg per kilogram of body weight) was administered to patients who had metastatic HER2-mutant NSCLC that was refractory to standard treatment. The primary outcome was objective response as assessed by independent central review. Secondary outcomes included the duration of response, progression-free survival, overall survival, and safety. Biomarkers of HER2 alterations were assessed. Results A total of 91 patients were enrolled. The median duration of follow-up was 13.1 months (range, 0.7 to 29.1). Centrally confirmed objective response occurred in 55% of the patients (95% confidence interval [CI], 44 to 65). The median duration of response was 9.3 months (95% CI, 5.7 to 14.7). Median progression-free survival was 8.2 months (95% CI, 6.0 to 11.9), and median overall survival was 17.8 months (95% CI, 13.8 to 22.1). The safety profile was generally consistent with those from previous studies; grade 3 or higher drug-related adverse events occurred in 46% of patients, the most common event being neutropenia (in 19%). Adjudicated drug-related interstitial lung disease occurred in 26% of patients and resulted in death in 2 patients. Responses were observed across different HER2 mutation subtypes, as well as in patients with no detectable HER2 expression or HER2 amplification. Conclusions Trastuzumab deruxtecan showed durable anticancer activity in patients with previously treated HER2-mutant NSCLC. The safety profile included interstitial lung disease that was fatal in two cases. Observed toxic effects were generally consistent with those in previously reported studies. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Lung01 ClinicalTrials.gov number, NCT03505710.).

Purpose Metachronous brain-only oligorecurrence in patients with non–small cell lung cancer (NSCLC) is a rare event with favorable prognosis, but the clinical outcome has not been fully determined. We retrospectively analyzed clinical outcomes and prognostic factors in metachronous brain-only oligorecurrence in patients with NSCLC who underwent definitive treatment.Materials and Methods We reviewed 4,437 NSCLC patients without oncogenic driver mutations who underwent definitive treatment between 2008 and 2018. Among them, we identified 327 patients who developed 1 to 5 brain metastases with or without systemic metastasis. Of the 327 patients, 71 had metachronous brain-only oligorecurrence without extracranial progression and were treated with local therapy to the brain. Overall survival (OS), progression-free survival (PFS), and prognostic factors affecting OS were analyzed.Results The median OS was 38.9 months (95% confidence interval [CI], 21.8 to 56.1 months) in 71 patients. The 2-year OS rate was 67.8% and the 5-year OS rate was 33.1%. The median PFS was 25.5 months (95% CI, 12.2 to 14.4 months). The longest surviving patient had a survival period of 115 months. Through multivariate analysis, Eastern Cooperative Oncology Group ≥ 1 (hazard ratio, 5.33; p=0.005) was associated with poor survival. There was no significant difference in OS between patients with local therapy and those with local plus systemic therapy (18.5 months vs. 34.7 months, p=0.815).Conclusion Metachronous brain-only oligorecurrence NSCLC patients who underwent definitive treatment experienced long-term survival with local therapy, highlighting the unique patient population. The role of systemic chemotherapy in this patient population requires further investigation.

Purpose This study aimed to evaluate the role of postoperative radiotherapy (PORT) in intracranial solitary fibrous tumor/hemangiopericytoma (SFT/HPC).Materials and Methods A total of 133 patients with histologically confirmed HPC were included from eight institutions. Gross total resection (GTR) and subtotal resection (STR) were performed in 86 and 47 patients, respectively. PORT was performed in 85 patients (64%). The prognostic effects of sex, age, performance, World Health Organization (WHO) grade, location, size, Ki-67, surgical extent, and PORT on local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) were estimated by univariate and multivariate analyses.Results The 10-year PFS, and OS rates were 45%, and 71%, respectively. The multivariate analysis suggested that PORT significantly improved LC (p < 0.001) and PFS (p < 0.001). The PFS benefit of PORT was maintained in the subgroup of GTR (p=0.001), WHO grade II (p=0.001), or STR (p < 0.001). In the favorable subgroup of GTR and WHO grade II, PORT was also significantly related to better PFS (p=0.028). WHO grade III was significantly associated with poor DMFS (p=0.029). In the PORT subgroup, the 0-0.5 cm margin of the target volume showed an inferior LC to a large margin with 1.0-2.0 cm (p=0.021). Time-dependent Cox proportion analysis showed that distant failures were significantly associated with poor OS (p=0.003).Conclusion This multicenter study supports the role of PORT in disease control of intracranial SFT/HPC, irrespective of the surgical extent and grade. For LC, PORT should enclose the tumor bed with sufficient margin.

Purpose Acute promyelocytic leukemia (APL) is a rare disease in children and there are some different characteristics between children and adult. We aimed to evaluate incidence, clinical characteristics and treatment outcomes of pediatric APL in Korea.Materials and Methods Seventy-nine pediatric APL patients diagnosed from January 2009 to December 2016 in 16 tertiary medical centers in Korea were reviewed retrospectively.Results Of 801 acute myeloid leukemia children, 79 (9.9%) were diagnosed with APL. The median age at diagnosis was 10.6 years (range, 1.3 to 18.0). Male and female ratio was 1:0.93. Thirty patients (38.0%) had white blood cell (WBC) count greater than 10×109/L at diagnosis. All patients received induction therapy consisting of all-trans retinoic acid and chemotherapy. Five patients (6.6%) died during induction chemotherapy and 66 patients (86.8%) achieved complete remission (CR) after induction chemotherapy. The causes of death were three intracranial hemorrhage, one cerebral infarction, and one sepsis. Five patients (7.1%) suffered a relapse during or after maintenance chemotherapy. The estimated 4-year event-free survival and overall survival (OS) rates were 82.1%±4.4%, 89.7%±5.1%, respectively. The 4-year OS was significantly higher in patients with initial WBC < 10×109/L than in those with initial WBC ≥ 10×109/L (p=0.020).Conclusion This study showed that the CR rates and survival outcomes in Korean pediatric APL patients were relatively good. The initial WBC count was the most important prognostic factor and most causes of death were related to serious bleeding in the early stage of treatment.

Purpose In 2017, the Children's Hepatic Tumors International Collaboration-Hepatoblastoma Stratification (CHIC-HS) system was introduced. We aimed to evaluate the accuracy of Children's Hepatic Tumors International Collaboration-Hepatoblastoma Stratification (CHIC-HS) System for the prediction of event-free survival in Korean pediatric patients with hepatoblastoma. Materials and methods This two-center retrospective study included consecutive Korean pediatric patients with histopathologically confirmed hepatoblastoma from March 1988 through September 2019. We compared event-free survival (EFS) among four risk groups according to the CHIC-HS system. Discriminatory ability of CHIC-HS system was also evaluated using optimism-corrected C-statistics. Factors associated with EFS were explored using multivariable Cox regression analysis. Results We included 129 patients (mean age, 2.6±3.3 years; female:male, 63:66). The 5-year EFS rates in the very low, low, intermediate, and high-risk groups, according to the CHIC-HS system were 90.0%, 82.8%, 73.5%, and 51.3%, respectively. The CHIC-HS system aligned significantly well with EFS outcomes (p=0.004). The optimism-corrected C index of CHIC-HS was 0.644 (95% CI, 0.561-0.727). Age ≥8 (vs. age ≤2; HR, 2.781; 95% CI, 1.187-6.512; p=0.018), PRE-Treatment EXTent of tumor (PRETEXT) stage IV (vs. PRETEXT I or II; HR, 2.774; 95% CI, 1.228-5.974; p=0.009), and presence of metastasis (HR, 2.886; 95% CI, 1.457-5.719; p=0.002), which are incorporated as the first three nodes in the CHIC-HS system, were independently associated with EFS. Conclusion The CHIC-HS system aligned significantly well with EFS outcomes in Korean pediatric patients with hepatoblastoma. Age group, PRETEXT stage, and presence of metastasis were independently associated with EFS.

Purpose This study aims to evaluate the prognosis of pathologically node-positive bladder cancer after neoadjuvant chemotherapy, the role of adjuvant chemotherapy in these patients, and the value of preoperative clinical evaluation for lymph node metastases.Materials and Methods Patients who received neoadjuvant chemotherapy followed by partial/radical cystectomy and had pathologically confirmed lymph node metastases between January 2007 and December 2019 were identified and analyzed.Results A total of 53 patients were included in the study. The median age was 61 years (range, 34 to 81 years) with males comprising 86.8%. Among the 52 patients with post-neoadjuvant/pre-operative computed tomography results, only 33 patients (63.5%) were considered positive for lymph node metastasis. Sixteen patients (30.2%) received adjuvant chemotherapy (AC group), and 37 patients did not (no AC group). With the median follow-up duration of 67.7 months, the median recurrence-free survival (RFS) and the median overall survival (OS) was 8.5 months and 16.2 months, respectively. The 2-year RFS and OS rates were 23.3% and 34.6%, respectively. RFS and OS did not differ between the AC group and no AC group (median RFS, 8.8 months vs. 6.8 months, p=0.772; median OS, 16.1 months vs. 16.3 months, p=0.479). Thirty-eight patients (71.7%) experienced recurrence. Distant metastases were the dominant pattern of failure in both the AC group (91.7%) and no AC group (76.9%).Conclusion Patients with lymph node-positive disease after neoadjuvant chemotherapy followed by surgery showed high recurrence rates with limited survival outcomes. Little benefit was observed with the addition of adjuvant chemotherapy.

Purpose This study was aimed to investigate long-term survivals and toxicities of early-stage nasopharyngeal carcinoma (NPC) in endemic area, evaluating the role of chemotherapy in stage II patients.Materials and Methods Totally 187 patients with newly diagnosed NPC and restaged American Joint Committee on Cancer/ International Union Against Cancer 8th T1-2N0-1M0 were retrospectively recruited. All received intensity-modulated radiotherapy (IMRT)±chemotherapy (CT) from 2001 to 2010.Results With 15.7-year median follow-up, 10-year locoregional recurrence-free survival, distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS) were 93.3%, 93.5%, 92.9% and 88.2%, respectively. Multivariable analyses showed cervical lymph nodes positive and pre-treatment prognostic nutritional index ≥ 52.0 could independently predict DMFS (p=0.036 and p=0.011), DSS (p=0.014 and p=0.026), and OS (p=0.002 and p < 0.001); Charlson comorbidity index < 3 points could predict DSS (p=0.011); age > 45 years (p=0.002) and pre-treatment lactate dehydrogenase ≥ 240 U/L (p < 0.001) predicted OS. No grade 4 late toxicity happened; grade 3 late toxicities included subcutaneous fibrosis (4.3%), deafness or otitis (4.8%), skin dystrophy (2.1%), and xerostomia (1.1%). No differences on survivals were shown between IMRT+CT vs. IMRT alone in stage II patients, even in T2N1M0 (p > 0.05). Unsurprising, patients in IMRT+CT had more acute gastrointestinal reaction, myelosuppression, mucositis, late ear toxicity, and cranial nerve injury (all p < 0.05) than IMRT alone group.Conclusion Superior tumor control and satisfying long-term outcomes could be achieved with IMRT in early-stage NPC with mild late toxicities. As CT would bring more toxicities, it should be carefully performed to stage II patients.

PURPOSE Most patients with mantle cell lymphoma (MCL) are older. In this study, we investigated the efficacy and safety of a chemotherapy-free combination with ibrutinib and rituximab (IR) in previously untreated older patients with MCL (age ≥ 65 years). METHODS We enrolled 50 patients with MCL in this single-institution, single-arm, phase II clinical trial ( NCT01880567 ). Patients with Ki-67% ≥ 50% and blastoid morphology were excluded. Ibrutinib was administered with rituximab up to 2 years with continuation of ibrutinib alone. The primary objective was to assess the overall response rate and safety of IR. In evaluable samples, whole-exome sequencing and bulk RNA sequencing from baseline tissue samples were performed. RESULTS The median age was 71 years (interquartile range 69-76 years). Sixteen percent of patients had high-risk simplified MCL international prognostic index. The Ki-67% was low (< 30%) in 38 (76%) and moderately high (≥ 30%-50%) in 12 (24%) patients. The best overall response rate was 96% (71% complete response). After a median follow-up of 45 months (interquartile range 24-56 months), 28 (56%) patients came off study for various reasons (including four progression, 21 toxicities, and three miscellaneous reasons). The median progression-free survival and overall survival were not reached, and 3-year survival was 87% and 94%, respectively. None of the patients died on study therapy. Notably, 11 (22%) patients had grade 3 atrial fibrillation. Grade 3-4 myelosuppression was seen in < 5% of patients. Differential overexpression of CCND1, BIRC3, BANK1, SETBP1, AXIN2, and IL2RA was noted in partial responders compared with patients with complete response. CONCLUSION IR combination is effective in older patients with MCL. Baseline evaluation for cardiovascular risks is highly recommended. Randomized trial is needed for definitive conclusions.

Background Sarcopenia is defined as either low pre-operative muscle mass or low muscle density on abdominal CT imaging. It has been associated with worse short-term outcomes after surgery for colorectal liver metastases. This study aimed to evaluate whether sarcopenia also impacts long-term survival outcomes in these patients. Methods A random-effects meta-analysis was conducted following the PRISMA guidelines. Overall survival (OS) and disease-free survival (DFS) outcomes were evaluated. Results Eleven studies were included, ten reporting on the impact of low muscle mass and four on low muscle density. Sample sizes ranged between 47 and 539 (2124 patients in total). Altogether, 897 (42%) patients were considered sarcopenic, although definitions varied between studies. Median follow-up was 21–74 months. Low muscle mass (hazard ration (HR) 1.35, 95%CI 1.08–1.68) and low muscle density (HR 1.97, 95%CI 1.07–3.62) were associated with impaired OS. Low muscle mass (pooled HR 1.17, 95%CI 0.94–1.46) and low muscle density (pooled HR 1.13, 95%CI 0.85–1.50) were not associated with impaired RFS. Discussion Sarcopenia is associated with poorer OS, but not RFS, in patients with CRLM. Additional studies with standardized sarcopenia definitions are needed to better assess the impact of sarcopenia in patients with CRLM.

Background Pretreatment and on‐treatment plasma cytokine levels in predicting clinical benefit in patients with advanced non‐small cell lung cancer (NSCLC) treated with anti‐programmed death‐1 (PD‐1)‐based chemotherapy is still a matter of debate. Methods We measured 12 kind of plasma cytokines in patients with stage III/IV NSCLC before and during treatment with anti‐PD‐1 based chemotherapy. Associations with best overall response, and survival including progression‐free survival (PFS) and overall survival (OS) were assessed using Chi‐square test and Kaplan–Meier plots with log‐rank test, respectively. Logistic regression and Cox regression were used to determine independent risk factors. Results Of a total of 60 patients, high‐level of pretreatment interleukin‐2 was associated with longer PFS (log rank p = 0.049), while high‐level of pretreatment interleukin‐8 was associated with shorter OS (log rank p = 0.006). Increased on‐treatment interleukin‐1β (IL‐1β) was associated with both better response (odds ratio [OR] 6.233, 95% confidential interval [CI]: 1.451–26.344, p = 0.013) and longer PFS (hazard ratio [HR] 0.305, 95% CI: 0.127–0.730, p = 0.008). On the contrary, increased on‐treatment interleukin‐6 (IL‐6) was associated with a worse response (OR 0.015, 95% CI: 0.001–0.400, p = 0.012), worse PFS (HR 2.639, 95% CI: 1.163–5.991, p = 0.020) and worse OS (HR 2.742, 95% CI: 1.063–7.074, p = 0.037). Increased interferon‐γ (IFN‐γ) was found to be associated with better PFS (HR 0.336, 95% CI: 0.153–0.745, p = 0.007). Conclusions In patients with advanced NSCLC who received chemoimmunotherapy, on‐treatment increased IL‐1β and IFN‐γ may serve as positive indicator of efficacy, while on‐treatment increased IL‐6 might play a predictive role of worse clinical outcome., We retrospectively measured 12 kind of plasma cytokines in patients with stage III/IV non‐small cell lung cancer before and during immune checkpoint inhibitor (ICI)‐based chemoimmunotherapy. Results showed that increased on‐treatment interleukin‐1β, interferon‐γ were related to longer progression‐free survival (PFS). Increased on‐treatment IL‐6 was related to shorter PFS. We suggest the indicative role played by circulating cytokines and efficacy of ICI‐based chemotherapy.

Aim Drug approvals for genome-informed indications have been increasing in recent years, but it is unknown how many of them have demonstrated an improvement in overall survival (OS). We assessed the frequency of approved genome-informed drugs demonstrating improvements in OS and progression-free survival (PFS) and whether the frequencies differed by cancer type. Materials and methods We searched all Food and Drug Administration approvals from 2006 to 2020, and for each drug that was approved for a genomic indication, we then searched on PubMed for randomised studies examining OS or PFS. Results We found 53 drugs approved for 92 unique indications from 2006 to 2020. We found that 50 drugs (55%) approved for a genomic indication had a randomised study evaluating OS benefit, and of those, only 22 demonstrated an improvement in OS. Similarly, 52 drugs (57%) evaluated PFS benefit, and 51 of these studies demonstrated an improvement in PFS. Drugs approved for BRAF V600 melanoma demonstrated an improvement in OS more often than drugs approved for ALK non–small cell lung cancer. The median improvement in OS was 4.7 months (range 1.5 months–49.1 months). Conclusion Although there is widespread enthusiasm for this class of agents, and many demonstrate impressive response rates, further trials or post-marketing studies are needed to ascertain the impact on survival and quality of life, the magnitude of these gains, and the cost-effectiveness of these agents.

Circulating tumor DNA (ctDNA) has demonstrated great potential as a noninvasive biomarker to assess minimal residual disease (MRD) and profile tumor genotypes in patients with non‐small‐cell lung cancer (NSCLC). However, little is known about its dynamics during and after tumor resection, or its potential for predicting clinical outcomes. Here, we applied a targeted‐capture high‐throughput sequencing approach to profile ctDNA at various disease milestones and assessed its predictive value in patients with early‐stage and locally advanced NSCLC. We prospectively enrolled 33 consecutive patients with stage IA to IIIB NSCLC undergoing curative‐intent tumor resection (median follow‐up: 26.2 months). From 21 patients, we serially collected 96 plasma samples before surgery, during surgery, 1–2 weeks postsurgery, and during follow‐up. Deep next‐generation sequencing using unique molecular identifiers was performed to identify and quantify tumor‐specific mutations in ctDNA. Twelve patients (57%) had detectable mutations in ctDNA before tumor resection. Both ctDNA detection rates and ctDNA concentrations were significantly higher in plasma obtained during surgery compared with presurgical specimens (57% versus 19% ctDNA detection rate, and 12.47 versus 6.64 ng·mL−1, respectively). Four patients (19%) remained ctDNA‐positive at 1–2 weeks after surgery, with all of them (100%) experiencing disease progression at later time points. In contrast, only 4 out of 12 ctDNA‐negative patients (33%) after surgery experienced relapse during follow‐up. Positive ctDNA in early postoperative plasma samples was associated with shorter progression‐free survival (P = 0.013) and overall survival (P = 0.004). Our findings suggest that, in early‐stage and locally advanced NSCLC, intraoperative plasma sampling results in high ctDNA detection rates and that ctDNA positivity early after resection identifies patients at risk for relapse., ctDNA profiling in plasma revealed higher levels and detection rates of ctDNA during tumor resection as compared to pretreatment time points in patients with early‐stage or locally advanced NSCLC. Moreover, patients testing positive for ctDNA immediately after tumor resection had worse clinical outcomes than patients with undetectable ctDNA. Our research highlights the role of ctDNA assessment for guiding treatment in patients with respectable NSCLC.

Background Non‐small cell lung cancer (NSCLC) is the leading cause of cancer‐related mortality worldwide. It is advisable to select the appropriate treatment based on characteristics of the cancer such as pathology, mutations, and programmed death‐ligand 1 (PD‐L1) levels. In this study, by remarking squamous NSCLC with low PD‐L1 expression without mutations, we investigated the efficacy and safety of regimens that included molecularly targeted drugs such as immune checkpoint inhibitors (ICIs) through a network meta‐analysis. Methods Databases were searched systematically to identify appropriate articles, in which randomized trials with incurable squamous NSCLC were described. Suitable studies were manually checked by two reviewers. A random model network meta‐analysis was conducted, in which the primary outcome was the overall survival rate. Results We identified 48 studies, which included 16 391 patients. When a platinum + third‐generation cytotoxic agent regimen (platinum regimen) was a reference, the platinum regimen + pembrolizumab (Pemb) yielded the best results in regard to the overall survival rate when compared with chemotherapy (hazard ratio [HR] = 0.57, 95% confidence interval [CI] = 0.36–0.90, p = 0.016) followed by the platinum regimen + nivolumab (Niv) + ipilimumab (Ipi) (HR = 0.61, 95% CI = 0.44–0.84, p = 0.003). However, the efficacy of ICI monotherapy was not statistically different from that of the platinum regimen. Conclusions The combination therapies, which were the platinum regimen + Pemb and the platinum regimen + Niv + Ipi, rather than ICI monotherapy were effective first‐line agents for treating squamous NSCLC with low PD‐L1 levels., Clinicians wonder which treatment is best for patients with squamous lung cancer expressing low programmed death‐ligand 1 and no mutations. This study presents the comparison of regimens including immune checkpoint inhibitors using network meta‐analysis with 48 studies and 16 391 patients. The primary outcome was overall survival. Our main result was that the platinum regimen + pembrolizumab was the best regimen (hazard ratio = 0.57, 95% confidence interval = 0.36–0.90, p = 0.016).

Objective To evaluate factors impacting survival outcomes in patients with uterine serous carcinoma (USC). Methods Data of consecutive patients diagnosed with USC undergoing surgery between 2000 and 2020 at Fondazione IRCCS Istituto Nazionale Tumori of Milan (Italy) were reviewed. Progression-free (PFS) and overall survival (OS) outcomes were evaluated using Kaplan-Meier and Cox proportional hazard models. Results Records of 147 consecutive patients meeting the inclusion criteria were analyzed. Stage distribution was: 67 (45.6%) patients with early-stage with uterine confined disease and 80 (54.4%) with advanced stages disease. Minimally invasive surgery was performed in 43 patients (29.5%). The median follow-up period was 78.6 months (IQ range = 35.7–117.3 months). The overall recurrence rate was 41% (60 patients): 19/67 patients (28.4%) with early-stage disease and 41/80 patients (51.3%) with advanced stage. The 5-year PFS rate was 35.0% (95% confidence interval [CI]: 27.5–44.7%). In multivariate analysis, age, BMI, depth of myometrial invasion, cytology, and optimal cytoreduction with postoperative residual tumor absent significantly impacted on PFS. The 5-year OS rates were 46.5% (95% CI: 38.1–56.8). The result of multivariate analysis showed that there was significant difference in OS based only on optimal cytoreduction and accuracy of retroperitoneal surgery. Conclusions In apparent early-stage USC, peritoneal and retroperitoneal staging allows to identify patients with disease harboring outside the uterus. Optimal cytoreduction is the most significant prognostic factor. Further collaborative studies are warranted in order to improve outcomes of USC patients.

Background: The efficacy of osimertinib as a first-line treatment for patients with poor performance status (PS) remains unclear. Patients & methods: This multicenter retrospective study evaluated patients treated with osimertinib between 2018 and 2020, with PS 2–4. Results: Among 36 patients with PS 2, the median progression-free survival (PFS), 1-year PFS, median overall survival (OS) and 1-year OS were 14.5 months, 65.4%, 18.1 months and 72.7%, respectively. Among 20 patients with PS 3–4, the median PFS, 1-year PFS, median OS and 1-year OS were 3.0 months, 27.1%, 5.0 months and 46.1%, respectively. Conclusion: Osimertinib was not as efficacious as other EGFR-tyrosine kinase inhibitors.

Background/purpose Several strategies have been reported for improving the integrity of transurethral resection of bladder tumor (TURBT). However, no standard has been established. Stratified TURBT (SR) is one of protocols for TURBT, wherein exophytic tumors are first resected and retrieved, and tumor bases are then resected. In this study, we aimed to evaluate the outcomes of SR in patients with nonmuscle invasive bladder cancer (NMIBC). Methods From January 2012 to December 2017, patients newly diagnosed as having NMIBC with a follow-up period of more than 2 years were enrolled and categorized into SR and conventional TURBT (CR) groups. Propensity score matching at a 2:1 ratio was performed. Outcomes were the detrusor muscle sampling rate, recurrence-free survival (RFS), and progression-free survival (PFS). Results In total, 205 patients were included in our study. The detrusor muscle sampling rate was higher in the SR group (P = 0.043). After propensity score matching, 162 patients were selected for outcome analysis, with 108 and 54 patients undergoing SR and CR, respectively. Compared with the CR group, the SR group showed a lower recurrence rate (P = 0.015) and better RFS in univariate (P = 0.010) and multivariate (P = 0.006) Cox proportional hazards regression. Progression rate and PFS were not significantly different between the two groups. Conclusion SR results in a higher detrusor muscle sampling rate and better disease outcomes. Our findings suggest that SR is a promising strategy for TURBT in patients with NMIBC.

Highlights • Brachytherapy boost is a standard of care for locally advanced cervical cancer. • High-dose-rate brachytherapy (HDR-BT) boost procedure is not standardized. • The number of implants, fractions, doses and imaging differ in literature. • Bi-fractionated HDR-BT in 1 implant is feasible with good oncological outcome. • Bi-fractionated HDR-BT dose escalation slightly increases acute toxicity., Purpose Brachytherapy (BT) boost after radio-chemotherapy (RCT) is a standard of care in the management of locally advanced cervical cancer (LACC). As there is no consensus on high-dose-rate (HDR) BT fractionation schemes, our aim was to report the oncological outcome and toxicity profile of four different schemes using twice-a-day (BID) HDR-BT. Patients and methods This was an observational, retrospective, single institution study for patients with LACC receiving a HDR-BT boost. The latter was performed with a single implant and single imaging done on day 1. The different fractionation schemes were: 7 Gy + 4x3.5 Gy (group 1); 7 Gy + 4x4.5 Gy (group 2); 3x7Gy (group 3) and 3x8Gy (group 4). Local (LFS), nodal (NFS) and metastatic (MFS) recurrence-free survival as well as progression-free survival (PFS) and overall survival (OS) were analyzed. Acute (≤6 months) and late toxicities (>6 months) were reported. Results From 2007 to 2018, 191 patients were included. Median follow-up was 57 months [45–132] and median EQD210D90CTVHR was 84, 82 and 90 Gy for groups 2, 3 and 4 respectively (dosimetric data missing for group 1). The 5-year LFS, NFS, MFS, PFS and OS were 85% [81–90], 83% [79–86], 70% [67–73], 61% [57–64] and 75% [69–78] respectively, with no significant difference between the groups. EQD210D90CTVHR

To understand the influence of histologic subtypes on the survival outcomes of intermediate-high and high-risk renal cell carcinoma (RCC) following nephrectomy.This study employed data files from the SEER Program to identify patients diagnosed with intermediate-high or high risk RCC and treated with nephrectomy. Unadjusted Kaplan Meier curves, and multivariable Cox regression analyses were applied to estimate the hazards of histologic types for overall survival (OS) and cancer-specific survival (CSS).OS was higher for chromophobe (HR=0.58, 95% CI 0.47-0.70; P.0001), similar for papillary (HR=0.90, 95% CI 0.80-1.02; P=.11) and worse for sarcomatoid (HR=3.17, 95% CI 2.70-3.72; P.0001) subtypes relative to the clear cell subtype. OS was lower in the high-risk disease (HR=2.35, 95% CI 2.01-2.74; P.0001) versus intermediate-high risk disease. CSS was higher for chromophobe (HR=0.47, 95% CI 0.35-0.63; P.0001), similar for papillary (HR=0.91, 95% CI 0.77-1.08; P=.28) and worse for sarcomatoid (HR=4.19, 95% CI 3.50-5.02; P.0001) subtypes relative to the clear cell subtype. CSS was lower for the high-risk disease (HR=2.86, 95%CI 2.39-3.43; P.0001) relative to intermediate-high risk disease.

Objective To compare oncological outcomes in women with lower uterine segment involvement (LUSI) in endometrial carcinoma (EC) stage ≥ II - staged by a minimally invasive surgery (MIS) versus laparotomy. Study design A retrospective multi-center cohort study. Univariate analysis, Kaplan-Meier survival and Cox proportional hazard analysis were performed to compare between women staged by MIS and those staged by laparotomy. Results Over a median follow-up period of 3 years (interquartile range, 1.5–6 years) 212 women were included, 68 (32.1%) were surgically staged by MIS. Stages of disease did not vary between MIS and laparotomy and were 32.1%, 51.9%, and 16.0%, in stages II, III and IV – respectively. Adjuvant radiation and chemotherapy rate did not differ between groups. Overall recurrence rate was comparable (p = 0.084). Locoregional recurrence rate was higher in the MIS group odds ratio 2.17, 95% confidence interval 1.19–4.20). Overall and progression free survival were similar in both groups (log rank test p = 0.08 and p = 0.912 respectively). In Cox regression model adjusting for age, comorbidities, tumor grade, stage and adjuvant therapy, route of surgery (MIS vs. laparotomy) was not associated with overall survival (p = 0.169). Conclusions In women with advanced EC and LUSI, although MIS is associated with locoregional recurrences, survival is comparable to laparotomy.

Purpose An increasing number of advanced non–small cell lung cancer (NSCLC) cases are being reported in the ageing population. However, studies on the use of afatinib in elderly patients are scarce. We conducted a prospective multicentre, single-arm, and open-label phase II trial for low-dose afatinib (30 mg/day) use in elderly patients with NSCLC with EGFR mutation to assess quality-of-life (QOL) and pharmacokinetic (PK)/pharmacogenomic (PGx) parameters. Patients and methods The primary end-point was the objective response rate (ORR), and the planned number of registered cases was 35, with a threshold ORR of 50%, an expected ORR of 75%, α of 0.05, and β of 0.1. Secondary end-points were progression-free survival (PFS), overall survival (OS), the incidence rate of adverse events (AEs), QOL survey (FACT-L), and trough plasma concentration of afatinib at steady state (Css) and at the occurrence of clinically significant AEs. Results The median age of the patients was 79 years. The ORR was 80.0% and the disease control rate was 91.4%. The median PFS and OS were 15.6 and 29.5 months, respectively. Four patients discontinued because of AEs. Treatment-related death was not observed. No significant change in QOL was observed at baseline and after 4, 8, and 12 weeks. Css was comparable with those in previous reports and was significantly higher in patients with grade 3 AEs. Direct correlations between afatinib treatment and PGx profiles were not observed. Conclusions An afatinib starting dose of 30 mg/day could be an effective and safe treatment option for elderly patients.

Background The aim of this study was to estimate the efficacy and safety of bevacizumab combined with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) in advanced non‐small cell lung cancer (NSCLC) patients. Methods We searched randomized controlled trials (RCTs) on bevacizumab combined with EGFR TKIs in the NSCLC Cochrane Library, Web of Science, PubMed and Embase. The data were extracted and assessed according to the Cochrane Handbook. We calculated the hazard ratio (HR), risk ratio (RR), and confidence interval (CI), and accomplished this meta‐analysis with Stata 14 software. Results Of 1301 articles scanned, five articles were involved in this meta‐analysis. We determined that compared with using EGFR TKIs alone, combination treatment significantly prolongs progression‐free survival (PFS) (HR = 0.61, 95% CI = 0.52–0.70; p