tbuckley/cabot-search huggingface dataset:
Conversion from radical esophagectomy to definitive chemoradiotherapy after neoadjuvant chemotherapy for advanced esophageal squamous cell carcinoma: Treatment options based on chemotherapy response.
Authors: Kiyoshi Narita, Eiji Higaki, Tetsuya Abe, Hironori Fujieda, Shingo Hashimoto, Shigenori Kadowaki, Masahiro Tajika, Takeshi Kodaira, Kei Muro, Yasuhiro Shimizu
Journal: Journal of Clinical Oncology (2025)

408 Background: Radical esophagectomy after neoadjuvant chemotherapy (NAC) is the established strategy for resectable advanced esophageal cancer. However, some patients convert to definitive chemoradiotherapy (dCRT) after NAC due to reasons such as their wishes or disease progression, and their prognosis remains uncertain. We aimed to investigate the prognosis of patients who converted to dCRT. Methods: Patients who underwent NAC for resectable advanced esophageal squamous cell carcinoma between 2006 and 2020 were enrolled retrospectively. The prognostic impact of subsequent treatment after NAC, planned surgery or conversion to dCRT, was compared. Results: We analyzed 686 patients, 70 who converted to dCRT (dCRT group) and 616 who underwent surgery (Surg group). The dCRT group had a poorer prognosis than the Surg group, with more advanced tumors and poorer response to NAC. Therefore, further analysis was conducted by categorizing patients as Responders (complete or partial response) and Non-responders (stable or progressive disease) to NAC. Among Responders in the dCRT group, 76.7% achieved a complete response, and the 5-year esophageal preservation survival rate was 66.9%. The 5-year survival rates for Responders were 77.5% and 71.3% in the dCRT and Surg groups. Multivariable analysis showed that dCRT did not worsen prognosis ( P = .706, hazard ratio = 1.13; 95% confidence interval, 0.59 to 2.16). Conversely, in Non-responders, dCRT had a significantly poorer prognosis, with 5-year survival rates of 22.3% and 45.1% in the dCRT and the Surg groups (P &lt; .001). Conclusions: For patients responding to NAC, conversion to dCRT is considered a potential treatment option. The possibility of chemoselection has been suggested in the choice of treatment for esophageal squamous cell carcinoma.
Association between adjuvant component of perioperative chemotherapy and survival outcomes in resected gastric cancer (GC).
Authors: Aravind Sreeram, Celine Yeh, Nicolas Toumbacaris, Marinela Capanu, Shoji Shimada, Ping Gu, Yelena Y. Janjigian, David Herman Ilson, Vivian E. Strong, Geoffrey Yuyat Ku
Journal: Journal of Clinical Oncology (2025)

378 Background: Perioperative chemotherapy is the standard of care for resectable GC but many patients do not proceed to or complete adjuvant chemotherapy (AC). It remains unclear whether AC following neoadjuvant chemotherapy (NAC) improves survival. Methods: Patients with GC who received NAC and underwent curative-intent gastrectomy from 2006-2022 were identified from an institutional database. Patients with mismatch repair-deficient/microsatellite instability-high tumors, GEJ tumors, M1 disease, neoadjuvant radiotherapy, total neoadjuvant intent treatment, incomplete NAC (&lt;66% of planned cycles), and incomplete data were excluded. A lymph node ratio (LNR) risk cutoff was determined using maximally selected rank statistics. Kaplan-Meier analysis with log-rank tests were used to compare overall survival (OS) and disease-free survival (DFS). Cox proportional hazards regression models were used to identify independent predictors of OS and DFS. All analyses were performed in R statistical software. Results: Of 340 patients included, 264 (78%) received AC. Most common reasons for incomplete AC were postoperative complications (20%), poor performance status (16%), minimal pathologic response to NAC (14%), patient choice (14%), and NAC toxicity (9%). Median follow-up was 6.4 years. In the overall cohort, there was no significant difference in OS (median 10 vs. 8.3 years; p=0.14) or DFS (7.0 vs. 7.5 years; p=0.12) between AC and non-AC groups. In node-negative (ypN-) patients (n=170), there was no association between receipt of AC and OS (12 vs. 10 years; p=0.6) or DFS (12 vs. 10 years; p=0.8). On univariable analysis, lack of AC receipt was not associated with shorter OS (p=0.3) or DFS (p=0.4). In the node-positive (ypN+) cohort (n=170), AC receipt was associated with significantly longer DFS (4.8 vs. 2.7 years; p=0.031) but not OS (5.5 vs. 2.8 years; p=0.071). However, on multivariate analysis, AC only showed a non-significant trend towards longer DFS (HR 0.77 [95% CI 0.49-1.19]; p=0.20). High-risk patients based on LNR (LNR&gt;0.0684; n=112) who received AC (n=87; 78%) had longer OS (p=0.033) and DFS (p=0.014). No such differences were observed in the low risk LNR subgroup (LNR&lt;0.0684; n=227). Conclusions: Following NAC, AC was not associated with improved survival in patients with ypN- GC. The association between AC and survival in ypN+ GC remains unclear but LNR may be used to identify patients with ypN+ disease who may benefit from AC. These observations require prospective validation but may have implications for clinical care and future trial design.
Young onset gastrointestinal cancer: A needs analysis.
Authors: Nicola Keohane, John V Reynolds, Emily Harrold, David James Gallagher, Sinead King, Chris Gleeson, Oana Deac, Nikolett Warner, Cathy Enright, Paul McCormick, Michael E Kelly, Maeve Aine Lowery
Journal: Journal of Clinical Oncology (2025)

383 Background: The global incidence of Young Onset ( YO) cancers diagnosed in adults under 50 years, is increasing for unknown reasons. YO Gastrointestinal (GI) cancers, which account for approximately 27% of newly diagnosed cancer cases and 37% of cancer deaths present distinct challenges in areas including sexual health, finance, career and family. We assessed the holistic needs of these patients through a mixed methods approach. Methods: A single institution needs analysis study was undertaken in YO GI patients diagnosed 2014-2024 through an anonymous survey and Focus Group Discussions (FGD). The surveys asked about their experiences of sexual health and function, psychosocial concerns, financial concerns, career developments and when in their cancer journey would they prefer to speak to a health care professional about these. FGD's used nominal group technique to deepen the analysis. Results: 88 participants responded via survey and 10 participated in a FGD. The average age at diagnosis was 43 years. 80% of participants reported they would have benefitted from a conversation about fertility, sexual health/function (82%) and financial supports (98%) at diagnosis. 93% of patients were out of work during cancer treatment with average length of time &gt; 1 year. Conclusions: This needs analysis highlights the importance of specialised clinical pathways for young onset GI cancer patients focusing on these unique and complex needs. Financial supports, conversations regarding sexual health/function, fertility preservation and psychosocial support are critical areas requiring structured intervention. 2014-2024 young onset SJH. UGI ( N=233) Colorectal (N=275) Clinical Stage at diagnosis Oeso Stage 4 = 39% Gastric stage 4 = 26% Stage 3= 46% Stage 4 = 20% Treatment intent % Radical =54% Palliative =38% Radical/Palliative = 8% Radical =75% Palliative 25% Mortality rate 66% 25% GI Survey results ( N=236) Support offered Y/N Preferred timing of support Sexual health/ function No=85% Yes =15% 82% At diagnosis Financial support No=95%Yes= 5% 98% At diagnosis Fertility preservation No = 65% Yes=35% 80% At diagnosis
Envafolimab in combination with lenvatinib and albumin paclitaxel for previously treated advanced GEJ adenocarcinoma: Latest analysis of a phase II, two-cohort study.
Authors: Xiaoying Zhao, Weijian Guo, Xiaodong Zhu, Wanjing Feng, Mingzhu Huang, Qirong Geng, Zhe Zhang, Xuedan Sheng
Journal: Journal of Clinical Oncology (2025)

375 Background: The combination of first-line chemotherapy and PD-1 has emerged as a standard treatment, enhancing the efficacy in advanced gastric/gastroesophageal junction (GEJ) cancer. The efficacy of the combination of second-line chemotherapy and PD-1/PD-L1 remains unclear. This study aims to observe the efficacy of Envafolimab (PD-L1 inhibitor ) plus tyrosine kinase inhibitors (TKIs) and second-line chemotherapy in the treatment of patients (pts) with advanced GEJ adenocarcinoma. Methods: Eligible pts with HER2-negative, microsatellite stable (MSS), advanced GEJ adenocarcinoma were enrolled in this study. Pts who never received PD-1 or PD-L1 inhibitors before would assign into Group A. Pts in Group B have failed first-line PD-1 antibody combined chemotherapy, with optimal efficacy as or above stable disease (SD). Pts in both groups received Envafolimab (200mg, hypodermic injection, days 1, 15, Q4W) combined with Lenvatinib (8mg/12mg, po, once a day) and albumin paclitaxel (100mg/m2, IV, days 1, 8 and 15, Q4W, up to 6 cycles) until disease progression, unacceptable toxicity, or pts refusal to continue treatment. The primary endpoint was objective response rate(ORR) per iRECISTv1.1, and the secondary endpoints included disease control rate (DCR), progression free survival (PFS), overall survival (OS) and safety. Results: From Oct 2022 to Apr 2024, 32 pts were enrolled. Both groups enrolled 16 pts equally, and 15 pts of each group were evaluable for efficacy analysis. The average ages were 60.07 ± 11.73 y and 50.13 ± 12.18 y in group A and B respectively. In group A, 7 pts had been tested for PD-L1 status, of which 2 (13.3%) was positive and 5 (33.3%) were negative. PD-L1 status was negative in 5(33.3%) pts, positive in 9 (60.0%), and untested in 1(6.7%) in group B. As of Sep 14, 2024, The ORR was 60.0% (9/15) in group A and 46.7% (7/15) in group B. The DCR was 100.0% (15/15) in both groups. After a median follow-up of 17.0 mo (IQR: 8.0-18.8) in group A, the mPFS was 8.2 mo (95% CI = 6.1-10.4), and the mOS was 14.8 mo(95% CI = 7.4-22.2). With median follow-up of 9.0 mo (IQR: 6.1-16.2) in group B, the mPFS was 5.9 mo (95% CI= 3.8-8.1) and the mOS was 11.5 mo (95% CI = 3.1-19.9). Overall incidences of adverse events (AEs) of any grade was 100% (30/30), and 80.0% (24/30) pts had ≥ grade 3 AEs during treatment. Most treatment-related adverse events (TRAEs) of grade ≥3 included decreased neutrophil count (73.3%), decreased leukocyte count (63.33%), Anemia (10%), febrile neutropenia (6.67%). Conclusions: In pts of advanced gastric cancer who have previously received PD-1 inhibitors or not, this second-line combination therapy demonstrates promising preliminary effects. Pts who have not previously received ICIs might benefit more from this combination therapy. Clinical trial information: NCT06030934 .
Impact of race on end-of-life care among patients with esophageal cancer.
Authors: Suriya Baskar, Chaula Desai, Udhayvir Singh Grewal
Journal: Journal of Clinical Oncology (2025)

337 Background: Esophageal cancer is an aggressive malignancy with rising incidence globally. Patients with advanced esophageal cancer suffer from a heavy burden of a wide array of symptoms including dysphagia and cachexia/anorexia, necessitating the need for focused symptom management and palliative care. Studies focused on other cancer types have shown that Black patients are more likely to receive aggressive care at end-of-life (EOL) and suffer from a decline in quality of life. We sought to investigate racial differences in EOL care among patients with advanced esophageal cancer in the US. Methods: The National Inpatient Sample (NIS) was queried to identify all hospitalizations with esophageal cancer utilizing ICD-10 codes C15x from 2016 to 2020. Hospitalizations of White and Black patients with documented inpatient mortality events were then extracted. Demographic and clinical data were analyzed using chi squared tests, independent sample t-tests, and binary logistic regression (adjusted for age, gender, and Charlson comorbidity index or CCI). Adjusted Odds ratios (aOR) are presented with 95% Confidence intervals (CI). Results: A total of 15,130 patients with esophageal cancer were included, of which 13,345 (88.2%) were White and 1785 (11.8%) were Black. Hospitalizations with White patients recorded higher age, more males, and higher comorbidities per CCI. Hospitalizations with Black patients had longer lengths of stay on average, higher total hospital charges, and significantly less likely to have a Do Not Resuscitate (DNR) code status (aOR 0.81, 0.74-0.9 95% CI). Rates of inpatient palliative care consultation at EOL were significantly lower among Black patients (aOR=0.53, 0.48-0.58 95% CI). Black patients were more likely to receive aggressive intervention at EOL demonstrated by rates of blood transfusion (aOR 1.9, 1.6-2.1 95% CI), mechanical ventilation (aOR 1.7, 1.5-1.8 95% CI), and vasopressor usage (aOR 1.4, 1.2-1.6 95% CI). Conclusions: We present a large retrospective analysis demonstrating significant racial disparities in EOL care amongst hospitalized patients with esophageal cancer. Black patients had longer lengths of stay, lower rates of palliative care consultation and DNR code status, and higher rates of aggressive interventions at EOL. These findings may have implications for improving health care decision making for EOL care amongst minority patients with esophageal cancer. WhiteN=13345 BlackN=1785 p-value Age (in years) 68.24±10.67 65.12±10.36 &lt;.001 CCI 9.4±3.3 8.6±3.9 &lt;.001 Mean length of stay (days) 7.5±11.3 10.4±22.8 &lt;.001 Total Cost (In thousands of dollars) 108.6±231.0 141.9±388.5 &lt;.001 Palliative Adjusted OR 60.9% 45.1% .53 (.48 - .58) &lt;.001 DNR Adjusted OR 63.8% 58.0% .81 (.74 - .90) &lt;.001 Blood transfusion Adjusted OR 13.0% 23.0% 1.9 (1.6-2.1) &lt;.001 Mechanical ventilation Adjusted OR 31.4% 45.9% 1.7 (1.5-1.8) &lt;.001 Vasopressor Adjusted OR 7.8% 10.6% 1.4 (1.2-1.6) &lt;.001
Genetic mutations and cytotoxic chemotherapy response for advanced solid tumors: A detailed analysis using the C-CAT database in Japan.
Authors: Naoya Ishibashi, Takashi Kamatani, Yusuke Kinugasa, Sadakatsu Ikeda
Journal: Journal of Clinical Oncology (2025)

130 Background: Chemotherapy regimens are selected based on information about the primary organ or its histological type and are administered based on the results of previous clinical trials. Even now, as cancer genomic research has progressed and precision medicine, which optimizes therapeutic interventions based on tumor genome profiling using next-generation sequencing(NGS), has become standard treatment, cytotoxic anticancer drugs still remain key drugs. We examined the real-world database of genomic and clinical information established by the national central datacenter, the Center for Cancer Genomics and Advanced Therapy (C-CAT) to systematically analyze the effects of mutations across multiple cancers and therapies. Methods: This study delineated the association between genetic mutations and the therapeutic efficacy of cytotoxic chemotherapy in advanced solid tumors in a real-world Japanese clinical context. We incorporated data from 15,474 patients enrolled in the C-CAT database between June 2019 and June 2022. We analyzed the overall response and time to next treatment (TNT) for genetic alterations and five categories of cytotoxic anticancer drugs in gastrointestinal cancers. Results: In the C-CAT data, gastrointestinal cancers were frequently registered, with colorectal cancer being the most common, followed by pancreatic cancer, esophageal/gastric cancer, and biliary tract cancer. For platinum-based drugs, in colorectal cancer, the presence of gene X was associated with not only a higher response rate but also a longer TNT (hazard ratio 0.82, p&lt;0.001). In the case of colorectal cancer and pancreatic cancer with KRAS gene mutations, the ORR was low, and the TNT was also short in the case of pancreatic cancer (hazard ratio 1.33, p&lt;0.001). Interestingly, when BRCA2 genes are mutant, TNT tended to be longer in many organs, suggesting that platinum-based drugs are effective across organs in carcinomas with BRCA2 mutations. Additionally, gene X showed differences in efficacy not only for platinum but also for antimetabolites and topoisomerase inhibitors. Moreover, KRAS mutation was observed in almost all pancreatic cancers and was a treatment-resistant mechanism for all platinum drugs and antimetabolites. Conclusions: This study demonstrated that the effects of cytotoxic anticancer drugs differ depending on genetic mutations. When determining chemotherapy regimens, considering not only the organ but also genetic mutations may enable more efficient drug selection.
A randomized phase II clinical trial evaluating the safety and efficacy of initial dose adjustment of zolbetuximab plus chemotherapy in patients with HER2-negative and CLDN18.2-positive unresectable advanced or recurrent gastric, gastroesophageal junction cancer or esophageal adenocarcinoma (GENTLE-Z).
Authors: Mashiro Okunaka, Momoka Furuoka, Masashi Wakabayashi, Hideki Furuya, Hideaki Bando, Kohei Shitara, Izuma Nakayama
Journal: Journal of Clinical Oncology (2025)

TPS504 Background: Zolbetuximab, a monoclonal antibody targeting CLDN18.2, was recently approved in Japan for patients with HER2-negative/CLDN18.2-positive metastatic gastric or gastroesophageal junction cancer (mGC/GEJC). On-target GI toxicities such as nausea and vomiting are commonly observed during first infusion, occasionally leading to early treatment discontinuation. Effective management of these toxicities is essential for the successful use of zolbetuximab in clinical practice. This study aims to assess whether omitting the loading dose in the first cycle can reduce zolbetuximab-related GI toxicities without compromise efficacy . Methods: GENTLE-Z is a prospective, open-label, multi-intuitional, randomized phase II trial designed to compare the safety and efficacy of fixed-dose of zolbetuximab without loading dose vs. the standard zolbetuximab dose in combination with first-line mFOLFOX6 or CAPOX for patients with HER2-negative/CLDN18.2-positive mGC/GEJC. Patients are randomly assigned (1:1) to receive either a fixed dose of zolbetuximab (400 mg/m 2 q2w or 600 mg/m 2 q3w) or standard zolbetuximab regimen (800 mg/m 2 loading dose followed by 400 mg/m 2 q2w or 600 mg/m 2 q3w) with chemotherapy. The primary endpoint is the vomit-free rate during cycle 1, and secondary endpoints include efficacy outcomes such as objective response rate, progression-free survival and overall survival. The sample size is set based on the hypothesis that omitting loading dose will improve the vomit-free rate from 50% to 75%. The planned sample size is 86 patients, with a one-sided alpha error of 5% and power of 75%, over an estimated enrollment period of 1.5 years. Enrollment has been ongoing since September 2024 across 55 sites in Japan. This trial is registered in Japan Registry of Clinical Trials (jRCTs031240347). Clinical trial information: jRCTs031240347.
Colorectal cancer care disparities in an urban diverse population: A tale of two hospitals in the nation’s capital.
Authors: John Marshall, Anteneh A. Tesfaye, Connor Shimberg, Chelsea Perelgut, Jialing Zhu, Chiranjeev Dash
Journal: Journal of Clinical Oncology (2025)

38 Background: Colorectal cancer (CRC) disparities by race and ethnicity are well-documented nationally. In the District of Columbia (DC), Black Americans have an 18% higher incidence and 46% higher mortality rate compared to overall rates among all races/ethnicities. These disparities often stem from long-standing inequities in the social determinants of health, which affect access to cancer prevention, early detection, and treatment. MedStar Georgetown serves a large, urban, diverse population at 2 hospitals: the MedStar Georgetown University Hospital (MGUH) and the MedStar Washington Hospital Center (MWHC). MWHC serves a higher proportion of minoritized patients (pts) with multiple social determinant barriers to care, including those without private health insurance. We hypothesized that disparities would be found in CRC pt care and outcomes when comparing MWHC with MGUH. Methods: We conducted a retrospective study of all CRC pts treated during the 2021-2023 period at MGUH and MWHC using the COTA real-world database. Pt demographics, insurance status, and selected clinical data, including but not limited to treatment site, disease stage, tumor molecular testing, and pt survival, were abstracted for analysis. Descriptive, bivariate, and multivariate analyses focused on gender, race/ethnicity, insurance status, receipt of tumor testing, and the interval between diagnosis and therapy initiation and explored survival by these factors in addition to the site of care (MGUH versus MWHC). Results: Of the 379 CRC pts receiving care at the Lombardi Comprehensive Cancer Center during the study period, 53% were treated at MGUH and 47% at MWHC. CRC pts at MWHC were more likely than CRC pts at MGUH to be Black Americans (65% vs. 28%, p&lt;0.001) and have 3 or more comorbidities (16% vs. 8%, p=0.22) but were less likely to have early onset CRC (p&lt;0.01) and be on private insurance (36% vs. 23%, p=0.01). Pts treated at advanced stages (stages 3-4) were similar between the two hospitals (64%). In spite of these differences, we did not find any differences between MWHC and MGUH in molecular tumor testing (83% vs. 86%, p=0.41), median time (days) to treatment initiation (28 vs. 26 days, p=0.18), or short-term survival (90% vs. 91%, p=0.95). In analyses comparing care/treatment-related factors with race/ethnicity and insurance status across the 2 hospitals, we did not find any statistically significant differences. Conclusions: Contrary to our expectations of finding significant cancer care disparities, we did not observe any differences in molecular tumor testing rates, time to initiation of therapy, or short-term survival by treatment site or race/ethnicity status. Our results suggest that integrated, specialized, guideline-concordant care in comprehensive cancer centers has the potential to eliminate CRC outcome disparities among pts diagnosed at these centers.