Median Overall Survival Research Articles

Cemiplimab monotherapy in Japanese patients with recurrent or metastatic cervical cancer.

In the phase 3 EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 study, cemiplimab significantly improved overall survival (OS) versus chemotherapy for patients with recurrent or metastatic cervical cancer who progressed after first-line platinum-based chemotherapy. We present a post hoc subgroup analysis of patients enrolled in Japan. Patients were enrolled regardless of programmed cell death-ligand 1 status and randomized 1:1 to cemiplimab 350 mg intravenously every 3 weeks or investigator's choice single-agent chemotherapy for up to 96 weeks. Primary endpoint was OS. Key secondary endpoints were progression-free survival (PFS) and objective response rate (ORR). Overall, 608 patients were randomized, of whom 56 (9.2%) were in Japan (cemiplimab, n = 29; chemotherapy, n = 27). The median (range) duration of follow-up was 13.6 (6.0-25.3) versus 18.2 (6.0-38.2) months for patients in Japan and for the overall population, respectively. Median OS (95% confidence interval [CI]) was 8.4 (7.0-not evaluable) and 9.4 (5.4-14.9) months for cemiplimab versus chemotherapy (hazard ratio [HR]: 0.86; 95% CI: 0.43-1.68). Median PFS (95% CI) was 4.0 (1.4-8.2) versus 3.7 (1.8-4.2) months with cemiplimab and chemotherapy (HR: 0.90; 95% CI: 0.50-1.61), respectively. ORR was 17.2% for cemiplimab and 7.4% for chemotherapy (odds ratio, 2.47; 95% CI, 0.44-13.99). Incidence of treatment-emergent adverse events at any grade was 79.3% for cemiplimab and 100% for chemotherapy. Grade ≥3 adverse events were 37.9% versus 66.7% with cemiplimab and chemotherapy, respectively. While acknowledging limitations inherent to a small subgroup analysis, the HR of 0.86 observed in Japanese patients suggests an emerging survival benefit despite a 4.6-month shorter median duration of follow-up versus the overall study population.

Follicular Lymphoma in Chile in the Adult Public Cancer Program: The Impact of Chemoimmunotherapy.

Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma (NHL) in the United States and Europe. However, data on FL from Latin America are scant. This study aims at better understand the clinical features, treatment patterns and outcomes of patients with FL in Chile. Of special interest was to evaluate POD24 as an adverse marker. We collected retrospective data from 722 patients 15 years or older diagnosed with FL and treated in 17 cancer centers in Chile between 2000 and 2019. Time to first treatment (TTFT), progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Cox proportional-hazard regression models were fitted to investigate prognostic factor. The median age at diagnosis was 62 with a female predominance (63%); 73% of patients had advance stage disease and 68% had bone marrow involvement; 63% had intermediate or high FLIPI scores. The 1-year TTFT rate was 96%, and 30% of patients received chemoimmunotherapy. Adding rituximab to chemotherapy was associated with a higher complete response (69% vs. 60%; p < 0.001) and superior median OS (16 vs. 8 years; p < 0.001). Patients who experience POD24 had an inferior median OS (2.4 vs. 15 years). Our study shows a female predominance in patients with FL in Chile and confirms superior response and survival outcomes with adding rituximab to chemotherapy. Our study also confirms a poor OS in patients who experience POD24.

Consolidation ALK Tyrosine Kinase Inhibitors Versus Durvalumab or Observation After Chemoradiation in Unresectable Stage III ALK-Positive NSCLC

IntroductionPatients with advanced ALK-positive NSCLC typically have poor response to immunotherapy; the benefit of consolidation durvalumab in patients with unresectable stage III ALK-positive NSCLC remains unclear. Herein, we compare the efficacy and safety of consolidation ALK tyrosine kinase inhibitor (TKI) versus durvalumab or observation after concurrent chemoradiation. MethodsWe conducted a retrospective study using a multicenter study of 17 institutions globally. Patients with unresectable stage III ALK-positive NSCLC treated between 2015 and 2022 were included. Patients received ALK TKI, durvalumab, or observation after concurrent chemoradiation. Real-world progression-free survival (rwPFS) and overall survival (OS) were estimated using Kaplan-Meier method. Treatment-related adverse events (trAEs) were classified by Common Terminology Criteria for Adverse Events version 5.0. Outcomes were assessed by multivariable Cox regression analysis. ResultsA total of 67 patients were included, of whom 39 (58%) were female. Median age was 57 (interquartile range: 49–67) years. Furthermore, 15 received consolidation ALK TKI, 30 received durvalumab, and 22 underwent observation. Baseline characteristics were similar across the three groups other than differences in race. After adjusting for stage, age, and nodal status, median rwPFS was significantly longer for ALK TKI (rwPFS not reached, 95% confidence interval [CI]: 22.7– not reached) versus durvalumab (11.3 mo, 95% CI: 8.9–18.5, hazard ratio [HR] = 0.12, 95% CI: 0.026–0.5, p-adjusted [p-adj] = 0.006) or observation (7.2 mo, 95% CI: 3.4–10.6, HR = 0.04, 95% CI: 0.009–0.2, p-adj < 0.0001). Durvalumab significantly improved median rwPFS compared with observation (HR = 0.37, 95% CI: 0.19–0.71, p-adj = 0.002). Median OS in the ALK TKI and durvalumab cohorts was significantly improved compared with patients on observation (ALK TKI-observation: p = 0.04; durvalumab-observation: p = 0.03). TrAE of any grade occurred in eight (53%) and 11 (37%) patients treated with ALK TKI and durvalumab, respectively. Grade greater than or equal to three trAEs occurred in 27% (n = 4) of patients treated with ALK TKI and 6.7% of patients treated with durvalumab. ConclusionsPatients with ALK-positive NSCLC experience significantly improved rwPFS when treated with consolidation ALK TKI therapy, surpassing outcomes found with either durvalumab or observation. Although both ALK TKI therapy and durvalumab offer an extension in OS compared with observation alone, it seems that ALK TKI therapy is the superior choice, underscoring its pivotal role in enhancing patient survival.

Survival Benefit of Lenvatinib Plus PD-1 Inhibitor with or Without HAIC in Advanced Hepatocellular Carcinoma Beyond Oligometastasis: a Multicenter Cohort Study.

The outcome between Lenvatinib plus programmed cell death protein-1 (PD-1) inhibitor and Lenvatinib in HCC beyond oligometastasis was unclear. In this multicenter, we compared the prognosis of Lenvatinib plus PD-1 inhibitor with Lenvatinib in HCC beyond oligometastasis. A total of 296 patients from six institutions were included. The patients were divided into two groups: (a) concurrent Lenvatinib plus PD-1 inhibitor treatment (Len+PD-1 group) and (b) Lenvatinib monotherapy (Len group). The primary endpoint was overall survival (OS), the second endpoint was progression-free survival (PFS) and efficacy. The median OS was 20.1 ± 1.2 (17.7-22.5) months and 15.7 ± 1.5 (12.8-18.6) months in the Len+PD-1 and Len groups, respectively. The 12-, 24-, and 36-month OS rates were 79.1%, 39.4%, and 10.7% in the Len+PD-1 group, and 76.3%, 29.7%, and 0% in the Len group, respectively. The OS and PFS rates of the Len+PD-1 group were significantly longer compared with the Len group (hazard ratio [HR], 0.88; 95% confidence index [CI], 0.49-0.94; P = 0.021) and (HR, 0.66; 95% CI, 0.50-0.87; P = 0.003). A subgroup analysis revealed that OS (HR, 0.57; 95% CI, 0.36-0.90; P = 0.016) was improved between the Len+PD-1 and Len groups with hepatic artery infusion chemotherapy (HAIC) treatment, whereas OS (HR, 1.11; 95% CI, 0.68-1.80; P = 0.689) was similar between the Len and Len+PD-1 groups without HAIC. Lenvatinib combined with PD-1 inhibitor significantly improves the survival of HCC beyond oligometastasis. For patients with HAIC, there was obviously significance between Len and Len+PD-1 groups.

Atezolizumab Plus Bevacizumab Treatment for Unresectable Hepatocellular Carcinoma: Real-life Experience from a Single Tertiary Centre in Spain and ALBI Score as a Survival Prognostic Factor.

Atezolizumab/bevacizumab (atez/bev) has been established as first-line systemic treatment for hepatocellular carcinoma (HCC). However, concerns regarding safety and efficacy have been raised, and no biomarkers to predict response have yet been identified. We aimed to evaluate the real-life experience of atez/bev in a Spanish tertiary hospital and identify factors associated with overall survival (OS). A prospective study of consecutive patients with HCC treated with atez/bev was conducted from December 2020 to December 2022. Efficacy was assessed through OS and progression-free survival (PFS), whereas safety was evaluated based on adverse events (AE). Twenty-three patients were included; 91% were males with a mean of 70 years. Thirteen patients were classified as having BCLC-C. The median treatment duration was 126 days (range=567). Median OS was 381 days (95%CI=205-557) with a cumulative probability of death of 13%, 30%, and 49% at 3, 6 and 12-month follow-up, respectively. The only factor associated with OS was the ALBI score (HR=5.03; 95%CI=1.3-19.1), which showed an AUROC of 0.906 (95%CI=0.78-1.00) for the risk of death at 18 months follow up. Median PFS was 141 days (95%CI=110-172). Twenty (86.9%) patients experienced AE, which in nine (39.1%) cases led to the definitive discontinuation of the treatment, four of them (17.4%) due to an AE grade 5. The initial experience with atez/bev at our center demonstrated poorer outcomes compared to the original trial (IMbrave150). A careful assessment of the ALBI score may serve as a crucial factor in the selection of systemic treatment for patients with HCC.

A retrospective evaluation of therapeutic efficacy and safety of chemoradiotherapy in older patients (aged ≥ 75 years) with limited-disease small cell lung cancer: insights from two institutions and review of the literature.

The standard treatment for patients in good general condition with limited-disease small cell lung cancer (LD-SCLC) is concurrent platinum/etoposide chemotherapy and thoracic radiotherapy (TRT). However, the efficacy and safety of chemoradiotherapy (CRT) in older patients with LD-SCLC has not been fully explored; moreover, the optimal treatment for this patient group remains unclear. This study aimed to investigate the feasibility and efficacy of CRT in older patients with LD-SCLC. From April 2007 to June 2021, consecutive older patients (aged ≥ 75 years) with stage I to III SCLC who received concurrent or sequential CRT at two institutions were retrospectively evaluated for efficacy and toxicity of CRT. A total of 32 older patients underwent concurrent (n = 19) or sequential (n = 13) CRT for LD-SCLC. The median ages of the patients in the concurrent and sequential CRT groups were 77 (range: 75-81) years and 79 (range: 76-92) years, respectively. The median number of chemotherapeutic treatment cycles was four (range, 1-5), and the response rate was 96.9% in all patients (94.7% in concurrent and 100% in sequential CRT groups). The median progression-free survival (PFS) and median overall survival (OS) for all patients were 11.9 and 21.1 months, respectively. The median PFS was 13.0 and 9.0 months in the concurrent CRT and sequential CRT groups, respectively, with no statistically significant difference (p = 0.67). The median OS from the initiation of CRT was 19.2 and 23.5 months in the concurrent and sequential CRT groups, respectively (p = 0.46). The frequencies of Grade ≥ 3 hematological adverse events were as follows: decreased white blood cell count, 20/32 (62.5%); decreased neutrophil count, 23/32 (71.9%); anemia, 6/32 (18.8%); decreased platelet count, 7/32 (21.9%); and febrile neutropenia, 3/32 (9.4%). Treatment-related deaths occurred in one patient from each group. Although hematological toxicities, particularly reduced neutrophil count, were severe, CRT showed favorable efficacy in both concurrent and sequential CRT groups. However, concurrent CRT may not be feasible for all older patients with LD-SCLC; accordingly, sequential CRT may be considered as a treatment of choice for these patients. Further prospective trials are warranted to identify optimal treatment strategies for this patient group.

293. OUTCOMES AFTER SURGICAL TREATMENT OF OESOPHAGOGASTRIC CANCER WITH SYNCHRONOUS LIVER METASTASES: A MULTICENTRE RETROSPECTIVE COHORT STUDY

Abstract Background Approximately 10-12% of patients with oesophageal and gastric cancer (OGC) present with oli-gometastatic metastases at diagnosis. It remains unclear if there is a role for radical surgery in these patients. We aimed to assess the outcomes of OGC patients who underwent simultaneous treatment for the primary tumour and synchronous liver metastases. Methods Patients with OGC who underwent surgical treatment between 2008 and 2020 for the primary tumour and up to five synchronous liver metastases aiming for complete tumour removal or ablation (i.e. no residual tumour) were identified from four institutional databases. The primary outcome was overall survival (OS), calculated with the Kaplan-Meier method. Secondary outcomes were disease-free survival and postoperative outcomes. Results Thirty-one patients were included with complete fol-low-up data in 30 patients. Twenty-six patients (84%) received neoadjuvant therapy followed by response evaluation. Median OS was 21 months [IQR 9-36] with a 2- and 5-year survival rates of 43% and 30%, respectively. While disease recurred in 80% of the patients (20 of 25 patients) after a radical resection, patients with a solitary liver metastasis had a median OS of 34 months. The number of liver metastases was a prognostic factor for OS (solitary metastasis aHR 0.330; p-value = 0.025). Thirty-day mortality was zero and complications occurred in 55% of the patients. Conclusion Long-term survival can be achieved in well-selected patients who undergo surgical resection of the primary tumour and local treatment of synchronous liver metastases. In particular, patients with a solitary liver metastasis seem to have a favourable prognosis.

The Association of Statin Use With Survival Outcomes in Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC) Treated With Androgen Receptor Targeted Therapies (ART)

BackgroundStatins may provide a compounded effect on ART by decreasing cholesterol levels thus decreasing de novo androgen synthesis and tumor cell viability. We investigated the clinical efficacy of concurrent statin use on outcomes of patients with mCRPC taking ART. MethodsA single-institution retrospective analysis of patients with mCRPC receiving ART from 2010 to 2021 was performed. Our primary outcome was PSA progression free survival (PFS), and our secondary outcomes were overall survival (OS). Patient characteristics were collected in addition to ART treatment course, statin treatment, and survival outcomes. Cox proportional hazards regression model was used to estimate hazard ratios (HR) for OS and PSA PFS and multivariable logistic regression to determine risk factors. Results153 patients with mCRPC treated with ART were included. A total of 67 patients (43.8%) received concurrent statins. Median PSA PFS was 20.4 months for patients that received statins versus 15.3 months for patients who did not receive statins. Median OS was 45.1 months for patients who received concurrent statins versus 29.7 months for patients who did not. On univariate and multivariate survival analyses, there was no statistically significant difference between groups for PSA PFS (HR 0.7; CI 0.44-1.1; P = .123) and OS (HR 0.67; CI 0.42-1.06; P = .089). ConclusionsOur analysis suggests that statins do not significantly improve clinical outcomes in patients with mCRPC. Ultimately, current understanding remains limited, and prospective studies are needed, but here we provide a cost-effective, timely, and selective preliminary analysis.

Characteristics and outcomes of salvage surgery after immune checkpoint inhibitor therapy for initially unresectable non-small cell lung cancer.

Immune checkpoint inhibitors (ICIs) improved the long-term survival outcomes in patients with advanced non-small cell lung cancer (NSCLC), whereas the role of salvage surgery after ICIs was unknown. The object of this study was to investigate characteristics and outcomes of patients who underwent salvage surgery after ICIs. Retrospective chart review was performed on the basis of our multi-institutional database in search of consecutive patients who underwent salvage surgery after ICIs for initially unresectable NSCLC between 2016 and 2022. Patient characteristics, intraoperative findings, perioperative outcomes, histopathological findings, progression-free survival (PFS), and overall survival (OS) were investigated. Fifteen patients with a median age of 71 years were included in the study. The surgical approach was open thoracotomy in 5 and robotic or thoracoscopic surgery in 10 patients. Resection was performed for primary lesions in 8 and metastatic lesions in 7 patients. Postoperative complication was noted in 1 patient with grade 1 phrenic nerve palsy. The median PFS was 47.9 months, and the median OS was not reached. Three-year PFS was 0% in those with metastatic lesions and 87.5% in those with primary lesions (P=0.12). Salvage surgery after ICIs may be associated with low perioperative morbidity and acceptable long-term outcomes in selected patients. Salvage resection of primary lesions may be associated with more favorable PFS than of metastatic lesions.

Comparison between Trans-Arterial Chemoembolization Followed by Stereotactic Body Radiation Therapy and Trans-Arterial Chemoembolization Alone in BCLC Stage B Hepatocellular Carcinoma: A Pilot Study.

Both Stereotactic Body Radiation Therapy (SBRT) and Trans-arterial Chemoembolization (TACE) are now being widely used to treat advanced hepatocellular carcinoma (HCC) and can improve tumor local control rates. We aimed at evaluating the efficacy and toxicity of combining SBRT and TACE in comparison to TACE alone in unresectable HCC. 42 unresectable Barcelona Clinic Liver Cancer (BCLC) stage B HCC Child Pugh (CP) A patients were randomized to receive either: TACE alone (Arm A) or TACE followed by SBRT (Arm B). Dose prescribed was 40Gy in 5consecutive daily fractions over 1 week . We compared the local control (LC), Progression free survival (PFS), overall survival (OS) and toxicity between the two arms. 22 patients were in arm A versus 20 patients in arm B with median follow up 20 months starting recruitment from April 2021 till January 2023. Both LC, PFS were significantly better in Arm B. Complete remission (CR) rate was 54.5% and 75% in Arm A and B, respectively. Median PFS was 16 months in Arm B compared to 11 months in Arm A (p =0.003). Median OS was not reached in both arms. Both arms had comparable toxicities. Adding SBRT to TACE in advanced HCC, is safe and feasible with better efficacy in terms of LC and PFS with comparable side effects, in comparison to TACE alone.

Effect of Treatment Delivery Schedule for Patients With Early-Stage Non-Small Cell Lung Cancer Treated With Stereotactic Ablative Radiation Therapy: A Population-Based Analysis

PurposeThe optimal stereotactic ablative body radiotherapy (SABR) delivery schedule in stage I non-small cell lung cancer (NSCLC) remains unclear. This population-based study investigated grade ≥ 2 toxicity rates, local failure (LF), and overall survival (OS) in patients treated with 48 Gy in 4 fractions scheduled every other day (QOD) versus daily with weekends (QDW) and consecutive daily without weekends (QD). Materials and MethodsBetween January 2019 and June 2022, treatment records using 48 Gy in 4 fractions were extracted from a provincial cancer registry and grouped by delivery as QOD, QDW, or QD. Toxicity events were recorded using CTCAE v5.0. The Kaplan-Meier method was used to compute OS while LF was calculated using cumulative incidence methods with death as a competing risk. Cox regression analyses and Fine-Gray modelling was used to assess for variables associated with OS and LF, respectively. ResultsOf 404 patients meeting study criteria, 190, 111, and 103 received QOD, QDW, and QD SABR, respectively. More patients receiving QDW SABR were medically inoperable and more patients receiving QD SABR had tumors abutting the chest wall. Median follow-up was 29.5 months (interquartile range [IQR] 19.2-38.4). Overall toxicity was low, with crude rates of acute and late grade ≥ 2 toxicity not being statistically different among the groups. No grade 4 or 5 toxicities were recorded. LF rates at 24 months were not different at 7.5% (95% confidence interval [CI] 3.7-11.3), 9.5% (95% CI 3.9-15.1), and 11.0% (95% CI 4.9-17.2) for the QOD, QDW, and QD groups, respectively (p = 0.60). QDW and QD schedules were not associated with LR. Similarly, no significant differences in median OS were found among the QOD, QDW, and QD groups at 47.5 months (95% CI 39.26-55,74), 52.7 (95% CI 34.7-70.7), and 49.0 months (95% CI 31.6-66.4), respectively. QDW and QD schedules were not associated with OS. ConclusionsThis population-based study demonstrated no statistically significant differences in grade ≥ 2 toxicity rates, LF, and OS for stage I NSCLC patients treated with lung SABR using 48 Gy in 4 fractions delivered QOD, QDW, and QD. Patient convenience and optimization of resources may be considered when choosing a lung SABR treatment delivery schedule.

Comprehensive Analysis of Metastatic Prostate Cancer: Real-World Data From the Middle East.

Metastatic prostate cancer (Pca) is a complex disease with diverse clinical characteristics and outcomes across the geographical distribution. Herein, we present a series of patients from the Middle East, aiming at identifying disease outcomes and prognostic factors specific to this regional context. This is a retrospective study of patients with metastatic Pca, diagnosed at King Hussein Cancer Center, Jordan, between 2006 and 2018. Survival was estimated using the Kaplan-Meier method and compared using the log-rank test. Factors that significantly affected overall survival (OS) in the univariable analysis were examined in a multivariable Cox regression analysis. A total of 188 patients with metastatic Pca were included in this analysis, of whom 168 (89%) had de novo metastatic disease. The median age at diagnosis was 68 years, 144 (77%) had bone metastasis, 32 (17%) had visceral metastasis, and 126 (67%) had high-volume disease. At a median follow-up of 67 months, the median OS was 44.3 months. The following factors predicted inferior OS in univariable analysis: smoking, normal BMI, high-volume disease, high alkaline phosphatase (ALP), previous local therapy for prostate, and orchiectomy versus medical androgen deprivation therapy (ADT). On multivariable analysis, high-volume disease (hazard ratio [HR], 1.92 [95% CI, 1.17 to 3.13]; P = .0094), high ALP (HR, 2.136 [95% CI, 1.38 to 3.31]; P < .001), and orchiectomy (HR, 2.40 [95% CI, 1.51 to 3.82]; P < .001) emerged as independent factors for inferior OS. Metastatic Pca outcomes in our population closely align with the global benchmark. High volume status, elevated ALP, and performance of surgical as opposed to medical ADT emerge as prognostic indicators of poor survival.

Grading severity of MVI impacts long-term outcomes after laparoscopic liver resection for early-stage hepatocellular carcinoma: A multicenter study

PurposeTo examine the relationship between microvascular invasion (MVI) grading severity and long-term outcomes in early-stage hepatocellular carcinoma (HCC) patients undergoing laparoscopic liver resection (LLR). MethodsPatients who had LLR for early-stage HCC were enrolled. According to the grading severity of MVI, patients were classified into M0, M1 and M2. Recurrence-free survival (RFS) and overall survival (OS) among the groups were compared. Univariate and multivariate Cox regression analyses were performed to identify independent risk factors of OS and RFS. ResultsAmong 233 patients, MVI grading as M0, M1, and M2 accounts for 122 (52.4 ​%), 84 (36 ​%), and 27 (11.6 ​%) patients, respectively. The median OS and RFS in patients with M0, M1, and M2 were 84.9, 40.1, and 25.2 months; and 76.9, 27.0, and 18.8 months, respectively. Multivariable analyses identified both M1 and M2 to be independent risk factors for OS and RFS. ConclusionGrading severity of MVI was independently associated with RFS and OS after LLR for early-stage HCC. Patients with MVI, especially those with M2, should receive stringent recurrence surveillance and active adjuvant therapy.

An Emulated Target Trial Case Study of Real-World Overall Survival With Second-Line Maintenance Niraparib Versus Active Surveillance in Patients With Recurrent Ovarian Cancer.

This retrospective real-world study compared overall survival (OS) between patients with BRCA wild-type (BRCAwt) recurrent epithelial ovarian cancer (OC) who received niraparib second-line maintenance (2LM) versus active surveillance (AS) using target trial emulation, cloning, inverse probability of censoring weighting (IPCW) methodology to minimize immortal time bias. Eligible patients from a United States-based, deidentified, electronic health record-derived database were diagnosed with epithelial OC (January 1, 2011-May 31, 2021), were BRCAwt, and completed second-line (2L) therapy (January 1, 2017-March 2, 2022). Patient data were cloned at index (2L last treatment date), assigned to niraparib 2LM and AS cohorts, and censored when treatment deviated from clone assignment. Follow-up was measured from index to earliest of study end (May 31, 2022), last activity, or death. Median OS (mOS) and hazard ratios were estimated from stabilized IPCW Kaplan-Meier curves and Cox regression models. Overall, 199 patients received niraparib 2LM, and 707 had their care managed with AS. Key characteristics were balanced across cohorts after cloning and stabilized IPCW. Median follow-up was 15.6- and 9.3-months pre-cloning. IPCW mOS was 24.1 months (95% CI: 20.9-29.5) and 18.4 months (95% CI: 15.1-22.8) in niraparib 2LM and AS cohorts, respectively (hazard ratio, 0.77; 95% CI: 0.66-0.89). This real-world study provides supportive evidence of an OS benefit for patients with BRCAwt recurrent OC who received 2LM niraparib monotherapy compared with those whose care was managed with AS. The analytic strategies implemented were useful in minimizing immortal time bias and measured confounding.

Gemcitabine, carboplatin, and Epstein–Barr virus-specific autologous cytotoxic T lymphocytes for recurrent or metastatic nasopharyngeal carcinoma: VANCE, an international randomized phase III trial

Epstein-Barr virus-specific cytotoxic T lymphocyte (EBV-CTL) is an autologous adoptive T-cell immunotherapy generated from the blood of individuals and manufactured without genetic modification. In a previous phase II trial of locally recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) patients, first-line gemcitabine and carboplatin (GC) and EBV-CTL combination demonstrated objective antitumor EBV-CTL activity and a favorable safety profile. The present study explored whether this combined first-line chemo-immunotherapy strategy would produce superior clinical efficacy and better quality of life compared with conventional chemotherapy treatment. This multicenter, randomized, phase III trial evaluated the efficacy and safety of GC followed by EBV-CTL versus GC alone as first-line treatment of R/M NPC patients. Thirty clinical sites in Singapore, Malaysia, Taiwan, Thailand, and the USA were included. Subjects were randomized to first-line GC (four cycles) and EBV-CTL (six cycles) or GC (six cycles) in a 1 : 1 ratio. The primary outcome was overall survival (OS) and secondary outcomes included progression-free survival, objective response rate, clinical benefit rate, quality of life, and safety. gov identifier: NCT02578641. A total of 330 subjects with NPC were enrolled. Most subjects in both treatment arms received four or more cycles of chemotherapy and most subjects in the GC+ EBV-CTL group received two or more infusions of EBV-CTL. The central Good Manufacturing Practices (GMP) facility produced sufficient EBV-CTL for 94% of GC+ EBV-CTL subjects. The median OS was 25.0 months in the GC+ EBV-CTL group and 24.9 months in the GC group (hazard ratio= 1.19; 95% confidence interval 0.91-1.56; P= 0.194). Only one subject experienced a grade 2 serious adverse event related to EBV-CTL. GC+ EBV-CTL in subjects with R/M NPC demonstrated a favorable safety profile but no overall improvement in OS versus chemotherapy. This is the largest adoptive T-cell therapy trial reported in solid tumors to date.

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...

249. OVERALL SURVIVAL OF PATIENTS WITH ESOPHAGEAL CANCER TREATED WITH DEFINITIVE CHEMORADIOTHERAPY: INSIGHTS FROM A RETROSPECTIVE STUDY

Abstract Background Neoadjuvant chemoradiotherapy followed by esophagectomy is the standard of care for patients with locally advanced esophageal cancer. However, definitive chemoradiotherapy (dCRT) may be considered as an alternative for those with unresectable disease, cervical location of the tumor or if a non-surgical approach is preferred based on the patient's condition. Heterogeneity in indications for dCRT makes it challenging to draw generalized conclusions regarding outcomes and survival. The aim of this study was to evaluate overall survival (OS) and recurrence patterns in patients with specified homogeneous indications for dCRT. Methods Patients with esophageal cancer treated with dCRT (50.4 Gy radiotherapy concomitant with 6 cycles of carboplatin/paclitaxel) between 2012-2022 in a tertiary referral center were identified from our institutional database. Primary endpoint was OS calculated from date of diagnosis until date of death or last day of follow-up, using the Kaplan Meier method. Secondary endpoints included the proportion of patients that completed the dCRT regimen, 30- and 90-day mortality following dCRT and disease recurrence. Results 162 patients were included, median follow-up was 74.6 months (IQR 46.2-99.3). The full dCRT regimen was completed by 116 (73.9%) patients. The 30- and 90-day mortality were 2.5% and 8.3%, respectively. The median OS was 23.7 months (95% CI 6.65-40.66) for cervical location of the tumor, 13.7 months (95% CI 7.92-29.8) for irresectable disease, 28.2 months (95% CI 12.10-44.22) for patients unfit for surgery and 20.6 months (95% CI 14.14-27.13) for those with preference for dCRT (p=0.15). Disease recurrence was observed in 74 patients (46%), located locoregional (46%), distant (19%) or both locoregional and distant (35%). Conclusion(s) Treatment with dCRT resulted in a 5-year OS of 35% and is associated with a high 90-day mortality. Disease recurrence was mostly locoregional located and was observed in 46% of patients. This emphasizes the critical necessity for enhanced treatment strategies centered on improving locoregional disease control.

Ten-Year Survivals of Right Thoracic vs Left Thoracic Approach for Esophageal Cancer

BackgroundEsophagectomy can be performed using various surgical techniques. The aim of this study was to understand the impact of surgery on long-term survival for esophageal cancer. MethodsBetween May 2010 and July 2012, 300 patients with esophageal cancer were randomly assigned to undergo esophagectomy with either a left or right thoracic approach. Disease-free survival (DFS) and overall survival (OS) were compared based on the per-protocol principle among 286 patients with esophageal squamous cell carcinoma determined by postoperative pathologic results (146 in the right and 140 in the left thoracic arms). ResultsThe median DFS was 92 months in the right thoracic arm and 41 months in the left thoracic arm (hazard ratio, 0.73; 95% CI, 0.54-0.99; P = .045), with a cumulative 10-year DFS of 47.6% and 37.5%, respectively. The median OS was 136 months in the right thoracic arm and 99 months in the left thoracic arm (hazard ratio, 0.75; 95% CI, 0.54-1.04; P = .081), with cumulative 10-year OS of 52.4% and 43.7%, respectively. DFS and OS were comparable between the 2 arms for patients without lymph node metastasis. Conversely, for patients with lymph node metastasis, 10-year DFS was 32.7% and 21.4%, respectively (P = .018), and 10-year OS of the right and left thoracic arms was 37.9% and 25.9%, respectively (P = .012). ConclusionsCompared with the left thoracic approach, patients who underwent esophagectomy through the right thoracic approach had better 10-year survival rates, and the survival benefit was significant for those with lymph node metastasis.

The Patterns of Failure and Prognostic Impact of Tumor Location in Patients Undergoing Reirradiation for Glioblastoma.

Introduction RTOG 1205 is the only randomized study to evaluate the safety and efficacy of reirradiation (reRT) in recurrent glioblastoma (GBM). While this study showed that reRT was safe and improves progression-free survival (PFS), an improved approach to reRT is still needed. In this study, we report on patterns of failure and outcomes in a cohort of patients with recurrent GBM who underwent reRT. We hypothesize that patients at high risk of leptomeningeal spread (LMS) are not good candidates for reRT due to the risk of treatment-related toxicity without clinical benefit. Methods In this retrospective study, patients with recurrent GBM who underwent reRT at a single institution from 2015-2023 were included. Sociodemographic, treatment, and outcomes data were collected via chart review. Time to progression was defined as the time from the start of reRT to progression per the Response Assessment in Neuro-Oncology (RANO) criteria. Overall survival (OS) was defined as the time from the start of reRT to death. PFS and OS were estimated using the Kaplan-Meier method. Results Thirteen patients with recurrent GBM who underwent reRT were identified. The median age at diagnosis was 58 years. Six patients (46.2%) had tumors that were O6-methylguanine-DNA methyltransferase (MGMT) methylated, four (30.8%) were MGMT unmethylated, and three (23.11%) had unknown MGMT status. Eight patients underwent repeat resection after recurrence and before reRT. Most patients (n=7) received 35 Gy in 10 fractions with concurrent bevacizumab, while other patients were treated with 25-40 Gy in 5-15 fractions with grade 1 or less acute toxicity. Three patients were treated with tumor-treating fields. The median follow-up was five months. Median PFS was three months [95% confidence interval (95% CI): one to four months] and median OS was five months (95% CI, 1-8 months) as compared to 7.1 months and 10.1 months, respectively, on RTOG 1205. Five patients developed LMS after reRT, one patient died before progression, and the remaining seven patients all developed progression within one centimeter of the recurrent tumor. Of the patients who developed LMS, all had tumors abutting the ventricles and three underwent resection 2-17 months before reRT. Conclusion Patterns of failure suggest a potential treatment selection approach for patients with recurrent GBM, in which patients at high risk of LMS (tumor abutting ventricles with or without recent surgery) should not undergo reRT, while patients at low risk of LMS are good candidates for reRT. Furthermore, reRT could be administered with reduced margins given that all non-LMS recurrences were within 1cm of the original tumor. Additional studies are needed to validate this approach.

Assessing Disease Control in Mismatch Repair-Proficient Colorectal Cancer With Peritoneal Metastases Treated With Immune Checkpoint Blockade-Based Combination Therapies

PURPOSE Metastatic colorectal adenocarcinoma (mCRC) with proficient mismatch repair (pMMR) is associated with poor response to cytotoxic chemotherapy in the refractory setting. Immunotherapy regimens using a combination of immune checkpoint blockade (ICB)–based combination therapies have shown promise, although few studies include patients with peritoneal metastases (PMs). This study sought to examine the disease control rate (DCR) and overall survival (OS) of patients treated with PM who were treated with ICB-containing regimens. METHODS Patients with pMMR metastatic colorectal cancer treated with ICB-based combination regimens after progression on first- and second-line therapy at The University of Texas MD Anderson Cancer Center from 2015 to 2022 were identified. Disease response within each metastatic site was determined. OS and DCR were calculated. RESULTS A total of 30 patients with PM, with or without other metastases, had a median follow-up on an ICB containing regimen of 8.5 months and a median follow-up until death or censoring of 13.3 months. The median OS was 16.7 (10.0-Not reported) months, and 18-month survival was 47%. Among patients treated for ≥6 months, DCR at 6 months at each metastatic site was 20% (2/10) for liver, 68% for peritoneum (13/19, P = .02 v liver), 50% for lung (5/10, P = .35 v liver), and 0% for retroperitoneal adenopathy (0/2, P = 1.00 v liver). CONCLUSIONS Among patients with mCRC, ICB-based combination regimens can provide disease control in the peritoneum in the majority of patients, and median OS compares favorably to standard-of-care therapy in the refractory setting. Patients with peritoneal disease should be included in future ICB trials since treatment options are otherwise limited.