5-year Progression-free Survival Research Articles

292. CHEMOTHERAPY AND CHEMORADIOTHERAPY FOR ADENOCARCINOMA OF THE OESOPHAGUS AND JUNCTION WITH OLIGOMETASTASES: RESULTS OF THE TNT-OES-1 TRIAL

Abstract Background Chemotherapy (FLOT) and chemoradiotherapy (CROSS) are both effective as neoadjuvant regimens for esophageal and junctional cancer. Total Neoadjuvant Therapy (TNT) aims to increase efficacy by combining chemotherapy with chemoradiotherapy. Although TNT is increasingly used in rectal cancer, there are no data on combining e.g. FLOT and CROSS in esophageal cancer. This phase-II study aimed to evaluate the feasibility and safety of the TNT FLOT-CROSS combination in esophageal and junctional adenocarcinoma patients with oligometastatic disease. Methods Patients with oligometastatic (defined as a maximum of four lesions in up to two organs, excluding lymph nodes) esophageal adenocarcinoma were treated with four biweekly cycles of FLOT followed by response evaluation (CT-scan). Patients without disease progression (RECIST v1.1) proceed to CROSS. Afterwards, response was assessed by CT-scan, endoscopy with biopsies and endoscopic ultrasonography with fine-needle aspiration on indication. The multidisciplinary tumor board discussed whether patients could proceed to four additional cycles of FLOT or local therapy of metastases and/or esophagectomy. Primary endpoint was tolerability of TNT FLOT-CROSS, defined as the proportion completing four cycles of FLOT and five cycles of chemoradiotherapy. Secondary endpoints included progression-free survival (PFS), disease control rate (DCR), toxicity and the proportion proceeding to local therapy of metastases and/or esophagectomy. Results Twenty patients (85% males, median age 62.5 years (interquartile range 58.3-66) were included of whom 16 (80%) had a single metastatic lesion. Eighteen patients (90%) successfully completed FLOT and fifteen (75%) completed TNT FLOT-CROSS (Figure 1). Toxicity mainly consisted of grade 1-2 leukopenia/neutropenia during FLOT, leading to treatment delay in twelve patients and dose-limiting of oxaliplatin in one patient. One patient had malaise grade 2. No grade 3-5 toxicities occurred during CROSS. Following TNT FLOT-CROSS, ten patients underwent four additional cycles of FLOT and toxicity resulted in treatment delay and dose reduction in seven patients and hospitalization in two patients. Six patients underwent esophagectomy of whom two underwent local treatment of metastases. The 1- and 2-year PFS was 56% and 48%. Three months after TNT FLOT-CROSS completion, DCR was 73%. Conclusion(s) This study showed that sequencing TNT FLOT-CROSS in patients with oligometastatic esophageal adenocarcinoma is feasible and comes with manageable toxicity and promising efficacy. In follow-up to this study, the TNT-OES-2 study will assess the efficacy and feasibility of TNT FLOT-CROSS and TNT CROSS-FLOT in patients with resectable nodal-positive adenocarcinoma of the esophagus or esophagogastric junction.

A Multicenter Analysis of Allogeneic Transplant Outcomes in Adults with Philadelphia-Like B-Cell Acute Lymphoblastic Leukemia in First Complete Remission

Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subset of B-cell ALL with a poor prognosis with conventional therapies. Diagnostic challenges and lack of standardized treatment protocols contribute to suboptimal outcomes. Additionally, while allogeneic hematopoietic cell transplantation (HCT) is frequently recommended in adults with Ph-like ALL given its high-risk nature, data supporting its role remains limited. We conducted a multicenter retrospective study evaluating outcomes of adult patients undergoing HCT in first complete remission (CR1) for Ph-like ALL compared to Philadelphia chromosome positive ALL (Ph-pos) and other B-cell Philadelphia negative (Ph-neg) ALL. Data was collected from five academic centers across the US, focusing on HCT outcomes for patients with ALL. Patients undergoing HCT in CR1 between 2006 and 2021 were included. Among 673 patients, 83 (12.3%) had Ph-like ALL, while 271 (40.3%) had Ph-pos and 319 (47.4%) had Ph-neg ALL. Outcomes following HCT in CR1 for Ph-like ALL were comparable to Ph-neg ALL, with no significant differences in 3-year overall survival (66% vs. 59%, P = .1), progression-free survival (59% and 54%, P = .1), or relapse rates (22% vs. 20%, P = .7). In contrast, Ph-pos ALL had superior outcomes; 3-year OS (75%, P < .001), PFS (70%, P = .001) and relapse (12%, P = .003), this is likely attributed to tyrosine kinase inhibitor therapy. Our study suggests that HCT, coupled with effective 2nd line therapies can possibly mitigate the poor prognosis associated with Ph-like ALL and offers promising outcomes for patients with Ph-like ALL.

386. SAFETY AND FEASIBILITY OF PERSONALIZED NEOANTIGEN DC VACCINES IN POSTOPERATIVE ESOPHAGUS SQUAMOUS CELL CARCINOMA: A PHASE 1B TRIAL

Abstract Background Immunotherapy, as a neoadjuvant treatment, currently stands at the forefront of esophageal squamous carcinoma research. Yet, the landscape of post-surgery adjuvant therapy remains largely unexplored, especially for patients who experience inadequate responses or develop resistance to initial immunotherapy. Addressing this gap, we have undertaken a single-center, single-arm, prospective, and exploratory clinical study. This study aims to evaluate the efficacy of a personalized neoantigen-loaded dendritic cell vaccine (Neo-DCVac) as a novel adjuvant treatment in ESCC patients who have previously undergone neoadjuvant immunochemotherapy (nICT). Methods Neo-DCVac was designed and administered to 12 ESCC patients undergoing radical mastectomy post-nICT. Tailored adjuvant therapy was based on tumor immune microenvironment (TIME) analysis, following Lam's Stratified Treatment Strategy. The immunization schedule included five doses at weeks 1, 2, 4, 6, and 8, with bi-monthly boosts during the consolidation phase, sustained over a year. Primary endpoints were safety and post-vaccination immune response. Secondary endpoints included 1- and 2-year overall survival (OS) and progression-free survival. T-cell response to neoantigen peptides was assessed using enzyme-linked immunospot (ELISPOT), flow cytometry, and enzyme-linked immunosorbent asssay (ELISA), alongside single-cell sequencing to explore the vaccine's efficacy mechanism. Results From April 2021 to October 2023, a total of 12 ESCC patients were enrolled. The occurrence of all-grade AEs was 38.5% (5/12), all of grade 1-2, with no dose-limiting toxicities. No treatment interruptions or treatment-related deaths were observed. Till October 27 2023, the median follow-up was 31.2 months. Survival analysis revealed 1-year and 2-year disease-free survival (DFS) and overall survival (OS) rates of 88.3%, 66.7%, and 100.0%, 91.7%, respectively. Patients with diver genes had a longer median DFS (not reached) compared with patients without diver genes (10.8 months, P = 0.001). Post-vaccine immunization, all patients showed a marked increase in peripheral blood T cell subtypes (CD3, CD4, CD8), with significant neoantigen peptide response in 75% (9/12) as evidenced by ELISPOT and ELISA tests. Single-cell sequencing coupled with CoNGA analysis revealed a distinct MAIT cell population, displaying 65 clonotypes and 146 cells with consistent GEX profiles and TCR sequences. GLIPH2 analysis on Neo-Vac immunotherapy patients identified shared peptide-MHC specificities, notably in patient ES0-01, and similar patterns in patients ES0-04 and ES0-07, suggesting T cell expansion and neoantigen-specific responses post-vaccination. Conclusions The neoantigen DC vaccine demonstrated favorable safety and exhibited notable efficacy in ESCC.

Recent update of proton beam therapy for hepatocellular carcinoma: a systematic review and meta-analysis.

Although access to proton beam therapy (PBT) is limited worldwide, its use for the treatment of hepatocellular carcinoma (HCC) is gradually increasing with the expansion of new facilities. Therefore, we conducted a systematic review and metaanalysis to investigate the updated evidence of PBT for HCC. The MEDLINE, EMBASE, Cochrane Library, and Web of Science databases were systematically searched for studies that enrolled patients with liver-confined HCC that were treated with PBT for a cure up to February 2024. A total of 1,858 HCC patients receiving PBT from 22 studies between 2004 and 2023 were selected for this meta-analysis. The median proportion of Child-Pugh class A was 86% (range, 41-100), and the median tumor size was 3.6 cm (range, 1.2-9.0). The median total dose ranged from 55 GyE to 76 GyE (median, 69). The pooled rates of 3- and 5-year local progression-free survival after PBT were 88% (95% confidence interval [CI], 85-91) and 86% (95% CI, 82-90), respectively. The pooled 3- and 5-year overall rates were 60% (95% CI, 54-66) and 46% (95% CI, 38-54), respectively. The pooled rates of grade 3 hepatic toxicity, classic radiationinduced liver disease (RILD), and non-classic RILD were 1%, 2%, and 1%, respectively. The current study supports PBT for HCC and demonstrates favorable long-term survival and low hepatic toxicities compared with other published studies on other radiotherapy modalities. However, further studies are needed to identify the subgroups that will benefit from PBT.

Dose Deintensified 3-Day Photon, Proton, or Brachytherapy: A Nonrandomized Controlled Partial Breast Irradiation Trial

BackgroundThe optimal approach for partial breast irradiation (PBI) is unknown. We investigated a novel de-intensified 3-fraction PBI regimen for photons, protons, and brachytherapy. MethodsA multicenter nonrandomized controlled trial with primary outcome of adverse cosmesis at 3 years versus pre-PBI. Eligibility criteria were ≥ age 50 years treated with breast-conserving surgery for node-negative estrogen receptor positive (ER+) invasive breast cancer or any ductal carcinoma in-situ (DCIS) measuring ≤ 2.5 cm. Photon and proton PBI were prescribed 21.9 Gy (RBE) and brachytherapy 21 Gy in 3 fractions. Radiotherapy technique and use of adjuvant endocrine therapy was selected at physician and patient discretion. ResultsBetween June 17, 2015 and July 13, 2017, 161 eligible patients were treated with photons (56), protons (49), or brachytherapy (56). Median patient age was 66.8 years. 126 (78.3%) had invasive breast cancer (all ER+) and 35 (21.7%) had DCIS (88.6% ER+). 54.0% of patients with invasive breast cancer and 25.8% of patients with ER+ DCIS initiated and adhered to prescribed endocrine therapy. The proportion of patients with adverse cosmesis (by trained nurse assessment) was 14.5% at baseline, 2.3% at 3 years (difference -12.2%, 95% CI (-100%, -6.4%)). Adverse cosmesis at last-follow-up, with median follow-up 5 years, was 5.7% by nurse assessment, 5.6% by panel assessment of digital photographs, and 5.2% by patient self-report. There were no observed clinically meaningful changes in other patient reported outcomes, and just two grade 2 or higher adverse events, both grade 2, in the brachytherapy cohort. 5-year local recurrence-free and progression-free survival were 98.0% and 95.5%, respectively. There were no local recurrences amongst 60 patients with invasive breast cancer and Ki67 ≤ 13.25%. ConclusionsDe-intensified 3-day PBI provided favorable disease control, tolerability, and cosmetic outcomes, meeting the pre-specified criteria for acceptability. This approach is an attractive option for small node-negative ER+ BC and DCIS patients. Trial registrationClinicalTrials.gov identifier NCT02453737

Cost-Utility Analysis of Stereotactic Body Radiation Therapy Versus Surgery for Patients With Stage I Non-small Cell Lung Cancer in Japan.

Stereotactic body radiation therapy (SBRT) for patients with operable stage I non-small cell lung cancer (NSCLC) is less invasive than surgery. However, differences in lifetime costs and patient outcomes remain unclear. In this study, a cost-utility analysis of SBRT compared with surgery for Japanese patients with operable stage I NSCLC was conducted. A partitioned survival model was constructed using each treatment arm's overall survival (OS) and progression-free survival (PFS) data. The data for the SBRT arm were extracted from the Japanese multicenter cohort study, which enrolled 678 medically operable patients with stage I NSCLC, and patient registry data were used for the surgery arm. The 5-year OS rate was 78.2% for SBRT and 74.8% for surgery from both studies. The 5-year PFS rate was 57.0% for SBRT and 63.4% for surgery. The quality of life values of PFS and progressive disease were obtained from domestic and overseas literature (PFS: 0.74, progressive disease: 0.65). The time horizon was set to 10 years. The expected costs and quality-adjusted life years for each treatment group were calculated. All costs are expressed in Japanese yen converted to US dollars (USD). SBRT was the dominant strategy, reducing treatment costs by 4,443.8 USD and increasing quality-adjusted life years by 0.131 compared with surgery. According to probabilistic sensitivity analysis, the probability of SBRT being dominant and cost-effective was 50.6% and 72.4%, respectively. Under the budget impact analysis, the total savings for the patients with stage I NSCLC in Japan was 6,252,870.0 USD (n = 1,407). SBRT is a more cost-effective option than surgery in patients with medically operable stage I NSCLC in Japan. Large-scale epidemiologic studies that reflect the latest clinical realities, such as OS/PFS, will be needed to validate this study's robustness.

Phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) SWOG S1609: the desmoid tumors

BackgroundDual inhibition using anti-programmed death-1 (PD-1) and anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) checkpoint inhibitors has proven effective in many cancers. However, its efficacy in rare solid cancers remains unclear. Desmoid tumors...

Effect of family history of cancer on postoperative survival in patients with non-small cell lung cancer.

Family history of cancer (FHC) has been reported to increase mortality of non-small cell lung cancer, mainly comprised of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). However, the impact of FHC on long-term survival remains controversial. This study aims to identify the impact of FHC on postoperative survival in LUAD and LUSC. Patients underwent lung resection for LUAD or LUSC in West China Hospital from 2009 to 2021 were enrolled. The 5-year overall survival (OS), lung cancer-specific survival (LCSS) and progression-free survival (PFS) were compared between the patients with and without FHC. Multivariable Cox regression was also performed. A total of 6,253 patients were enrolled, including 5,685 LUAD and 568 LUSC. Altogether 18.9% (1,077/5,685) patients had FHC in LUAD, and 12.7% (72/568) patients had FHC in LUSC. In LUAD, the patients with FHC showed comparable survival compared with the patients without FHC regarding 5-year OS (87.9% vs. 86.5%, P=0.49), 5-year PFS (84.8% vs. 80.9%, P=0.06), and 5-year LCSS (89.2% vs. 88.0%, P=0.96). In LUSC, the patients with FHC had poorer survival compared with the patients without FHC according to 5-year OS (40.9% vs. 68.2%, P=0.007), 5-year PFS (42.3% vs. 66.2%, P=0.003), and 5-year LCSS (45.8% vs. 72.7%, P=0.003). Multivariate analyses indicated that FHC was an independent prognostic factor of OS, PFS, and LCSS in the patients with LUSC. FHC was associated with a poor survival after lung resection in LUSC not LUAD patients. More attention should be paid in postoperative monitoring and treatment in LUSC patients with FHC.

Combination of neutrophil-to-lymphocyte ratio and serum CA 19-9 as a prognostic factor in pancreatic cancer.

Traditionally, serum carbohydrate antigen 19-9 (CA 19-9) has been used as a key biomarker for pancreatic cancer and recently other biomarkers which reflect the systemic immune and inflammatory responses also have been explored as potential prognostic factors. The study aims to evaluate the significance of pretreatment neutrophil-to-lymphocyte ratio (NLR) and serum CA 19-9 as prognostic factor in pancreatic cancer patients. A retrospective analysis was conducted in 153 consecutive patients with pancreatic cancer in Instituto Nacional de Cancerología from 2013 to 2018. Pretreatment NLR and serum CA 19-9 values were recorded as well as survivals. The cut-off value determined for NLR was 2.4 and for serum CA 19-9 was 553 U/mL. Survival analysis showed that the 5-year overall survival (OS) was 9% in patients with low-NLR compared with 2% for patients with high-NLR (P=0.008), and 5-year progression-free survival (PFS) was 5.7% in patients with low-NLR compared with 1.3% in patients with high-NLR (P=0.007). For patients with low-CA 19.9, 5-year OS was 8.5% compared with 0% for patients with high-CA 19-9 (P=0.002), and 5-year PFS was 4.1% in patients with low-CA 19-9 compared with 0% in patients with high-CA 19-9 (P=0.005). Classification groups created showed that 5-year OS in Group 1 (low-NLR and low-CA 19-9) was 11.8% compared with 1.9% for patients in Group 2 (either one or both high-NLR or CA 19-9) (P<0.001), and 5-year PFS was 8.6% in Group 1 and 0% in Group 2 (P=0.001). High-NLR and high-CA 19-9 values used separately are both independently associated with worse OS and PFS in patients with pancreatic cancer. The classification groups created combining both biomarkers showed better prognostic significance than when used separately as demonstrated by survival analysis and multivariate analysis.

Clinical treatment strategy and follow-up of lymphoepithelioma-like carcinoma: a retrospective study.

Aim: To investigate the clinical features, diagnosis and treatment of lymphoepithelioma-like carcinoma (LELC).Materials & methods: The clinical data of 114 LELC patients were retrospectively analyzed.Results: Ninety-eight patients (86.0%) were Epstein-Barr virus-encoded small RNA (EBER) positive detected by situ hybridization. A 67.1% (51/76) patients had PD-L1 expression. The 5-year overall survival rate of EBER negative patients was 51.6% while the rate of positive patients was 84.8% (p=0.015). The 5-year progression free survival rate of EBER negative patients was 40.2% while the rate of positive patients was 70.2% (p=0.004).Conclusion: The progression of LELC is relatively slow and present a better prognosis. The occurrence of tumor is closely related to Epstein-Barr virus infection and PD-L1 is highly expressed in tumor cells.

Neutrophil-to-lymphocyte ratio as a predictor of progression in patients with early-stage cervical cancer

Aims: The neutrophil-to-lymphocyte ratio (NLR) has shown promise as a prognostic marker in various cancers, but its role in early-stage cervical cancer is not well defined. This study evaluates the association between pre-treatment NLR and progression risk in patients with early-stage cervical cancer. Methods: This retrospective study included 220 patients with stage I and II cervical cancer treated from 2010 to 2024. Patients with prior treatment, infection at diagnosis, or hematological diseases were excluded. Pre-treatment NLR was calculated from blood counts taken within a week before treatment. Primary outcome was progression-free survival (PFS). Cox regression analyses identified prognostic factors. Results: The median follow-up was 46 months (range, 1-120). Disease progression occurred in 17.3% of patients, and 15% died. The 5-year overall survival and PFS rates were 84.8% (95% CI: 79.3-90.3) and 77.7% (95% CI: 71.4-84), respectively. Univariate analysis identified non-squamous cell carcinoma (non-SCC) histology, tumor size &gt;4 cm, and elevated NLR as significant factors affecting PFS. Multivariate analysis confirmed non-SCC histology (HR: 3.2, p=0.002), tumor size &gt;4 cm (HR: 2.3, p=0.007), and elevated NLR (HR: 1.1, p=0.041) as independent PFS risk factors. Higher NLR correlated with larger tumor size. Conclusions: Elevated pre-treatment NLR independently predicts disease progression in early-stage cervical cancer. Incorporating NLR into risk stratification could enhance prognostic assessments and guide personalized treatments. Larger prospective studies are needed for validation.

Effect of Nivolumab on the Quality of Life in Recurrent/Metastatic Head and Neck Cancer.

Nivolumab is expected to further prolong survival and improve the quality of life (QOL) of patients with a poor prognosis of head and neck cancer. However, only a few studies have been conducted regarding the QOL of recurrent or metastatic head and neck cancer patients treated with nivolumab using real-world data. This study aimed to examine the effect of nivolumab on the QOL of these patients using real-world data. This study included patients with recurrent metastatic head and neck cancer who received nivolumab at the Department of Otolaryngology and Head and Neck Surgery, Tokyo Medical University Hospital from May 1, 2017, to December 31, 2021. Among them, 50 patients who self-assessed their QOL were included in this study. The primary endpoint was the QOL evaluation score, and secondary endpoints were overall survival (OS), progression-free survival (PFS), response rate, and immune-related adverse events. OS and PFS were evaluated using the Kaplan-Meier method. No significant reduction in QOL was observed before or after nivolumab administration. The median OS time was 20.1 months, and 1-year OS rate was 76.4%. The median PFS time was 4.2 months, and 1-year PFS rate was 31.0%. The comparison of patient QOL before and after nivolumab use suggested that patient QOL was not compromised. The results were not inferior to those of other studies in terms of treatment efficacy and safety.

Monitoring pediatric CNS non-germinomatous germ cell tumors via cerebrospinal fluid circulating tumor DNA.

Accurate molecular and clinical stratification of patients with central nervous system (CNS) non-germinomatous germ cell tumors (NGGCTs) remains challenging, impeding the development of personalized therapeutic approaches. Herein, we investigated the translational significance of cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) in pediatric NGGCTs to identify characteristic features of CNS NGGCTs and to identify a subset of patients for whom the presence of residual disease is a risk factor and an indicator of shorter progression-free survival (PFS) and overall survival (OS). Medical records of patients with CNS NGGCTs between January 1, 2018 and December 31, 2022 were reviewed retrospectively. The cohort consisted of 11 male and six female patients. Tumor markers were elevated in four of the five people who underwent surgery. The remaining 12 patients were diagnosed with malignant NGGCTs according to elevated tumor markers. Among them, ctDNA before chemotherapy as well as ctDNA clearance were consistently associated with PFS and OS (p<.05). By setting a ctDNA positivity threshold of 6%, patients with high ctDNA (above the threshold) levels, which had limitation due to the selection based on optimal statistic from the survival analysis, had significantly inferior 5-year PFS and OS compared to those with low levels (below the threshold). ctDNA or ctDNA clearance combined with the presence of residual disease predicted significantly worse OS and PFS (p<.05). CSF ctDNA might allow the study of genomic evolution and the characterization of tumors in pediatric NGGCTs. CSF ctDNA analysis may facilitate the clinical management of pediatric NGGCT patients, and aid in designing personalized therapeutic strategies.

Pan-immune-inflammation value: a new prognostic index in epithelial ovarian cancer

BackgroundEpithelial ovarian cancer (EOC) is one of the deadliest gynaecological malignancies worldwide. The aim of this retrospective study was to create a predictive scoring model based on simple immunological and inflammatory parameters to predict overall survival (OS) and progression-free survival (PFS) in patients with EOC.MethodsWe obtained 576 EOC patients and randomly assigned them to the training set (n = 405) and the validation set (n = 171) in a ratio of 7:3. We retrospectively evaluated the association between PIV and OS and PFS using a novel immunoinflammatory marker, according to the optihmal treshold of PIV, we divided the patients into two different subgroups, high PIV (PIV > 254.9) and low PIV (PIV ≤ 254.9). Pan-immune Inflammatory Value (PIV) was computed as follows: neutrophil count (109/L) × platelet count (109/L) × monocyte count (109/L)/lymphocyte count (109/L). Then developed a simple score prediction model based on several independent prognostic parameters using Cox regression analysis. We used receiver operator characteristic (ROC) curves, calibration plots, and decision analysis (DCA) curves to evaluate the performance of the model. Finally, we used Kaplan-Meier curves to ensure that the model could distinguish well between low- and high-risk groups.ResultsThere was a significant difference in survival outcomes between high PIV (PIV > 310.2) and low PIV (PIV ≤ PIV310.2) (3-year survival rates of 61.34% and 76.71%, respectively); 5-year OS, 25.21% and 51.14%, respectively; 3-year PFS, 40.90% and 65.30%; 5-year PFS, 19.33% and 39.73%, respectively). Column plots of OS and PFS were constructed using independent prognostic factors. In the training module, the 3-, 5-, and 10-year AUCs for OS and PFS column charts were 0.713, 0.796, 0.839, and 0.730, 0.799, 0.826, respectively.In the validation cohort, the 3-, 5-, and 10-year AUCs for OS and PFS column charts were 0.676, 0.803, 0.685, and 0.700, respectively, 0.754, 0.727. The calibration curves showed good agreement between predicted survival and actual observations. The decision analysis curves also showed that the current model has good accuracy and clinical applicability. 3-year OS was 61.34% and 76.71%, respectively; 5-year OS was 25.21% and 51.14%, respectively; 3-year PFS was 40.90% and 65.30%, respectively; 5-year PFS was 19.33% and 39.73%, respectively.ConclusionsWe constructed and validated a PIV-based nomogram to predict OS and PFS in EOC patients, with a view to helping gynaecologists converge on oncologists in their treatment and follow-up expertise in epithelial ovarian cancer.

Treatment outcomes between cyclosporin and chemotherapy in adult subcutaneous panniculitis-like T-cell lymphoma: a report from nation-wide Thai lymphoma study group registry.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of T-cell lymphomas with a characteristic feature of subcutaneous nodules associated with hemophagocytic lymphohistiocytosis (HLH). Treatment options for SPTCL are mainly chemotherapy (CMT) or immunosuppressive agents with selection currently dependent on physician decisions. Outcomes between the 2 treatment remedies have not yet been comprehensively compared. This study aimed to compare complete remission (CR) rates between SPTCL patients receiving cyclosporin (CSA)-based regimen (CSA +/- steroid) and CMT. The 5-year overall survival (OS) and 5-year progression free survival (PFS) were also analyzed. Clinical data from patients with SPTCL were drawn from the Thai Lymphoma Study Group registry who were newly diagnosed between 2007 and 2023. A total of 93 patients were selected with 45 cases having received CSA-based regimen and 48 cases having received CMT. There were more patients with limited stage at skin in the CSA group (63.8% vs. 36.2%, p = 0.003), while more patients with hepato- and/or splenomegaly were found in the CMT group (56.2% vs. 24.5%; p = 0.002). Germline HAVCR2 mutations were detected in 26/33 (78.8%) cases. The CR rate was significantly higher in patients treated with CSA (87% vs. 58.3%; OR = 6.5 [95%CI, 2.7-15.3]; p = 0.002). At a median follow-up of 87.8 months (range 0-185), the 5-year OS (98% vs. 87%, p = 0.19) and PFS (72.4% vs. 69.2%, p = 0.19) showed a trend favoring patients treated with CSA. Based on our study, CSA-based regimens are the preferred first-line treatment remedy for newly diagnosed SPTCL, especially in patients with limited cutaneous involvement.

Pembrolizumab and Cabozantinib in Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: Long-term Survival Update with a Biomarker Analysis.

Anti-programmed cell death protein 1 (PD-1) therapy is a standard of care in recurrent and/or metastatic head and neck squamous cell carcinoma (RMHNSCC). Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) have immunomodulatory properties and improve clinical outcomes in combination with anti-PD-1 therapy in different malignancies. We report the long-term efficacy and safety of pembrolizumab and cabozantinib in patients with RMHNSCC and include a correlative biomarker analysis. This open-label, single-arm, multicenter, phase 2 study screened 50 patients with RMHNSCC, of whom 36 received pembrolizumab and cabozantinib. The primary endpoint was overall response rate (ORR), safety, and tolerability. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and correlative studies of tissue and blood. We report the long-term PFS, OS, and safety of treated patients and describe correlative biomarkers evaluating p-MET expression and tumor immune microenvironment (TIME) using multiplex immunohistochemistry. With median follow-up of 22.4 months, the median PFS was 12.8 months with a 2-year PFS of 32.6% (95% CI, 18.8%-56.3%) and the median OS was 27.7 months with a 2-year OS of 54.7% [95% confidence interval (CI), 38.9%-76.8%]. The median duration of response was 12.6 months with a 2-year rate of 38.5% (95% CI, 30.8%-81.8%). Long-term treatment-related adverse events included manageable hypothyroidism (5.5%) and grade 1 elevated aspartate aminotransferase and alanine aminotransferase (2.8%). Baseline tumor p-MET expression correlated with ORR (P = 0.0055). Higher density of CD8+, CD103+, and CSF1-R+ cells at baseline correlated with improved OS [hazard ratio (HR) = 5.27, P = 0.030; HR = 8.79, P = 0.017; HR = 6.87, P = 0.040, respectively]. Pembrolizumab and cabozantinib provided prolonged encouraging long-term disease control and survival with a maintained favorable safety profile. The prognostic significance of higher density of CD8+, CD103+, and CSF1-R+ cells in TIME deserve further evaluation in similar clinical settings.

Toripalimab plus chemotherapy and radiotherapy for treatment-naive advanced esophageal squamous cell carcinoma: a single-arm phase 2 trial

This single-arm phase 2 trial (ChiCTR2100046715) examined previously untreated patients with advanced esophageal squamous cell carcinoma (ESCC) who received four cycles of paclitaxel with carboplatin every 3 weeks. Toripalimab was infused intravenously every 3 weeks for 12 months, or until disease progression or intolerable toxicity. Radiotherapy that encompassed the primary lesions and metastases commenced in the third cycle. The median progression-free survival time was 9.8 months (95% confidence interval [CI]: 6.8–not estimable) in the intent-to-treat population, failing to meet the pre-specified primary endpoints. Secondary endpoints included an objective response rate of 45.5%, a disease control rate of 57.6%, and a median duration of response of 11.5 months (interquartile range, 6.4–15.0). The 1-year progression-free survival and overall survival rates were 41.9% (95% CI: 27.7–63.5) and 69.7% (95% CI: 55.7–87.3), respectively. Lymphopenia was the most frequent grade ≥3 adverse event (82%), and an esophageal fistula developed in three patients (9.1%). No treatment-related deaths occurred. In prespecified exploratory biomarker analysis, higher densities of CD8 + T cells, CD11c+ dendritic cells, and CD68+ macrophages correlated with improved tumor response and prognosis. Radiotherapy supplementation to first-line chemo-immunotherapy for treatment-naive advanced ESCC demonstrated some antitumor activity and manageable safety profiles, warranting further randomized controlled trials.

Omission of Radiotherapy in Primary Mediastinal B-Cell Lymphoma: IELSG37 Trial Results.

The role of consolidation radiotherapy in primary mediastinal B-cell lymphoma (PMBCL) patients is controversial. The IELSG37 trial, a randomized non-inferiority study, aimed to assess whether irradiation can be omitted in PMBCL patients with complete metabolic response (CMR) after induction immunochemotherapy. Primary endpoint was progression-free survival (PFS) at 30 months post-randomization. Patients with CMR were randomly assigned to observation or consolidation radiotherapy (30 Gy). With a non-inferiority margin of 10% (assuming a 30-month PFS of 85% in both arms), a sample size of 540 patients was planned with 376 expected to be randomized. The observed events were considerably lower than expected, therefore, primary endpoint analysis was conducted when ≥95% of patients were followed for ≥30 months. Of 545 patients enrolled, 268 were in CMR after induction and were randomized to observation (n=132) or radiotherapy (n=136). The 30-month PFS was 96.2% in the observation arm and 98.5% in the radiotherapy arm, with a stratified hazard ratio of 1.47 (95%CI, 0.34 to 6.28) and absolute risk difference of 0.68% (95%CI, -0.97% to 7.46%). The 5-year overall survival was 99% in both arms.Non-randomized patients were managed according to local policies. Radiotherapy was the only treatment in 86% of those with Deauville score (DS) 4 and in 57% of those with DS 5. The 5-year PFS and OS of patients with DS 4 (95.8% and 97.5%, respectively) were not significantly different from those of randomized patients. Patients with DS5 had significantly poorer 5-year PFS and OS (60.3% and 74.6%, respectively). This study, the largest randomized trial of radiotherapy in PMBCL, demonstrated favorable outcomes in patients achieving CMR with no survival impairment for those omitting irradiation.

The effect of increasing the prescribed dose in stereotactic body radiotherapy for primary lung cancer without lymph node metastasis.

This study aimed to identify the efficacy of increasing the dose of stereotactic body radiotherapy (SBRT) for lung cancer. Patients who received SBRT for primary lung cancer between 2002 and 2021 were evaluated retrospectively. The patients were categorized into the 48, 50, and 55 Gy groups according to the prescribed dose. Analyses were performed for all matched patients. A total of 323 patients underwent SBRT for lung lesions at doses of 48, 50, and 55 Gy in four fractions. The median follow-up period in the 55 Gy group (32.3 months; Interquartile range (IQR), 15.1-54.1 months, P = 0.01) was significantly shorter than in the 48 Gy (47.0 months; IQR, 16,2-107.7 months) and 50 Gy (78.9 months; IQR 47.2-104.2 months) groups. The 3-year local progression-free survival (LPFS) was 90% in the 55 Gy group (95% confidence interval (CI), 62.4%-94.0%), 75.7% in the 48 Gy group (62.1%-85.0%), and 79.1% in the 50 Gy group (62.2%-89.1%). LPFS in the 55 Gy group was significantly higher than that in the 48 Gy group (hazard ratio (HR), 0.40; 95% CI, 0.20-0.79; P = 0.025). There is no significant difference in the local control rate between the 55 Gy group and the 50 Gy group (HR 0.60, CI 0.27-1.39). After propensity score matching, the 3-year LPFS in the 55 Gy group was 88.3% (CI, 71.2-95.5%). LPFS in the 55 Gy group did not significantly differ from that of the 48 Gy group (HR, 0.47; CI, 0.17-1.35) and the 50 Gy group (HR, 0.83; CI, 0.28-2.51). We conducted the analysis using propensity score matching. It was not apparent whether there was a significant difference in the effect of increasing the dose, owing to a lack of power caused by the small number of cases after propensity score matching. A prospective study is in progress, and the results are awaited.

Comparison of immunochemotherapy followed by surgery or chemoradiotherapy in locally advanced esophageal squamous cell cancer

BackgroundSeveral studies have shown that the survival outcomes of chemoradiotherapy (CRT) are not inferior to surgery alone in patients with esophageal squamous cell carcinoma (ESCC). This study aimed to compare survival outcomes of ESCC treated with immunochemotherapy (ICT) followed by surgery or definitive CRT and to explore subgroups of patients who could benefit from one treatment strategy. MethodsPooled data were obtained from two prospectively registered clinical trials of patients with ESCC at the Affiliated Cancer Hospital of Nanjing Medical University. One trial involved treatment with neoadjuvant ICT followed by surgery, while the other involved induction ICT followed by definitive CRT. To balance potential biases, we conducted an overlap weighting (OW) analysis to compare the rates of 2-year progression-free survival (PFS), locoregional relapse-free survival (LRRFS), distant relapse-free survival (DRFS), and overall survival (OS). Additionally, propensity score matching (PSM) was performed to analyze failure pattern. ResultsThe median follow-up time of the survivors was 39.3 months. After overlap weighting, the rates of 2-year PFS, LRRFS, DRFS, and OS for patients undergoing surgery and CRT were 61.5 % and 59.7 %, 67.2 % and 69.9 %, 81.3 % and 90.7 %, 84.6 % and 79.1 %, respectively (P>.05 for all). A trend for improved 2-year OS was observed in the surgery group in patients who did not respond to ICT (P=.07). ConclusionThe differences in the rates of 2-year PFS, LRRFS, DRFS, and OS between the surgery group and the chemoradiotherapy group did not reach statistical significance.