tbuckley/cabot-search huggingface dataset:
Associations of postdiagnosis changes in physical activity with all-cause mortality among patients with stage I-IIA colorectal cancer.
Authors: Karel Smit, Jeroen W.G. Derksen, Anne-Sophie van Lanen, Evertine Wesselink, Dieuwertje E. Kok, Ellen Kampman, Fränzel J.B. van Duijnhoven, Miriam Koopman, Anne M. May
Journal: Journal of Clinical Oncology (2024)

87 Background: Several observational studies show an association between physical activity (PA) at diagnosis and reduced risk of mortality among colorectal cancer (CRC) patients, but there has been limited research examining the potential benefit of changes in PA levels after CRC diagnosis. Here we investigate the association between change of PA and all-cause mortality in patients with stage I-IIA CRC receiving resection with curative intent. Methods: Data were used from two large Dutch CRC cohort studies (PLCRC &amp; COLON), which assessed PA at diagnosis (T0), six (T6) and twelve (T12) months after diagnosis, using the SQUASH questionnaire. A total of 2540 stage I-IIA CRC patients with repeated PA measures (i.e. a T0 and at least a T6 or T12 questionnaire) were used for this analysis. Total PA was quantified by calculating Metabolic Equivalent Task (MET) hours per week and categorized as low, moderate, and high PA, based on tertiles of an age- and sex-matched sample of the general population. PA changes were evaluated at T6 and T12 relative to T0. Being active was defined per timepoint as being in the moderate or high total PA group, or adhering to the PA guideline (minimum of 150 minutes per week of moderate-intensity PA). Cox proportional hazards models were used to study the association between PA variables and all-cause mortality, adjusted for age, sex, BMI, and tumor location (colon vs rectum). Results: Median follow-up time was 35 months (interquartile range 19 – 55) during which a total of 133 deaths occurred. Being active at both T0 and T6 compared to being inactive at these timepoints, was associated with a lower rate of all-cause mortality for both PA variables (adjusted hazard ratio (HR) 0.39 [95% confidence interval 0.24-0.63] and 0.41 [0.23-0.72] for total PA and guideline adherence, respectively). Similar results were found when comparing T12 to T0 (being active according to total PA HR 0.20 [0.09-0.42] and guideline adherence HR 0.31 [0.14-0.72]). Changing to either activity or inactivity at T6 or T12 was not significantly associated with all-cause mortality (Table). Conclusions: Maintaining a physically active lifestyle following surgery for stage I to IIA CRC is associated with longer overall survival, reinforcing the recommendations for physical activity. [Table: see text]
Impact of DNA mismatch repair status on prognosis of patients with locally advanced gastric cancer in a Mexican population.
Authors: Maria del Consuelo Diaz Romero, Sayako Mariana Miyagui-Adame, German Calderillo Ruiz, Erika Ruiz-Garcia, Marytere Herrera, Alberto Leon-Takahashi, Leonardo Lino-Silva, Luis Adrián Espinoza Ruelas, Elizabeth García, Stefan Zilli Hernandez
Journal: Journal of Clinical Oncology (2024)

408 Background: Gastric cancer (GC) is among the five most frequent and mortal cancers in the world. In Mexico, GC is the second cause of death from cancer in men between 30 and 59 years old. The role of deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) in locally advanced gastric cancer (LAGC) is still controversial. We aimed to evaluate the overall survival (OS) of patients with LAGC, according to MMR status and treatment. Methods: Retrospective study included patients from the National Cancer Institute of México, with locally advanced gastric adenocarcinoma diagnosis between 2008 and 2017. The Kaplan Meier, Log Rank, and Cox Regression methods were used to analyze the relation between MMR status and overall survival in LAGC. MMR status was assessed using immunohistochemistry. Results: A total of 103 patients with LACG were enrolled for analysis. The prevalence of dMMR in GC was 13.59% (n=14). The median OS was 101.9 months in the dMMR group vs. 86.2 months in the proficient MMR (pMMR) group (HR 0.54, 95% CI 0.19 - 1.52, p=0.23), with a 3-year OS of 71.4% vs 65.1% respectively. Survival was also analyzed according to MMR status and choosing treatment. OS was 106.8 months in the dMMR surgery alone group, 78.4 months in the dMMR group treated with both surgery and chemotherapy, 33.1 months for pMMR group with surgery alone, and 89.2 months in the pMMR group treated with surgery plus chemotherapy (p=0.014). Conclusions: In this analysis, OS tended to improve in dMMR group. pMMR surgery alone patients had a superior OS than other groups, while adding chemotherapy to surgery treatment seems to have a role only in pMMR patients. [Table: see text]
Characterizing the rare abdominal neoplasms of peritoneum, retroperitoneum, and overlapping sites of peritoneum and retroperitoneum: A review of NCDB database.
Authors: Baqir Jafry, Syed Mohammad Ali Kazmi
Journal: Journal of Clinical Oncology (2024)

764 Background: The tumor characteristics of the rare abdominal tumors including peritoneum (PT), retroperitoneum (RT) and overlapping sites of peritoneum and retroperitoneum (OT) remain unexplored. Methods: From the National Cancer Database, we identified all patients who were diagnosed with tumors in PT, RT or OT from 2004 to 2016. We evaluated the incidence of each tumor across time and compared population characteristics of each of these tumors. Results: We identified a total of 47300 patients - 22090 had PT, 11837 had RT and 13373 had OT. The mean age of PT was 66.9 while that of RT and OT was 61.2 and 68.1 respectively. All three cancers had a higher percentage of females compared to males (93.8% for peritoneum; 50.4% for retroperitoneum; 50.6% for overlapping sites), whites (88.8% for PT; 83.6% for RT; 81.5% for OT), insured patients (97.8% for PT; 96.2% for RT; 96% for OT) and patients without any existing comorbidities (75.9% for PT; 77.5% for RT; 67.7% for OT). The most common histology was adenocarcinoma in OT, leiomyosarcoma in RT, serous epithelial carcinoma among the PT population. These neoplasms had higher proportions of grade 3 tumors (58% for PT; 32.2% for RT; 50.9% for OT), patients with income &gt; $63,333 (38.6% for PT; 38.1% for RT; 36.6% for OT), and patients residing in an area where 6.3%-10.8% did not graduate from high school (29.8% for PT; 29.7% for RT; 23.8% for OT). From 2004 to 2016, there was a significant increase in the number of tumors of overlapping sites (566 in 2004 to 1848 in 2016) while the number of PT (1580 in 2004 to 1586 in 2016) and RT (726 in 2004 to 980 in 2016) did not change significantly. Conclusions: Among the rare abdominal neoplasms, the number of OT have increased from 2004-2016 while that of PT and RT tumors have remained stable. The histology patterns are consistent with known cancers that involve these regions.
Impact of facility volume on outcomes in patients with pancreatic cancer treated with radiotherapy.
Authors: Arvind Rajan, Elizabeth Gleeson, Veronica Pham, Benjamin Ethan Bodek, Karyn A. Goodman
Journal: Journal of Clinical Oncology (2024)

644 Background: The impact of facility volume on overall survival (OS) outcomes in patients with pancreatic cancer (PC) treated with radiotherapy (RT), both standard chemoradiation (CRT) and stereotactic body radiation therapy (SBRT) is not well-defined. Methods: This retrospective study analyzed 16,315 patients with locally advanced (LA) or borderline resectable (BR) PC from the National Cancer Database (2004-2019) who received neoadjuvant RT or RT without surgery across RT facilities with low- (&lt;10 cases/yr), intermediate- (10-20 cases/yr), and high-volumes (&gt;20 cases/yr) of PC cases. Log rank and cox regression were used for univariable and multivariable survival analysis, and Kaplan-Meier curves were generated. Results: Patients were largely treated at low (n=8055) volume centers, followed by intermediate (n=3783), and high (n=4477). Approximately half of the cohort were male (51.4%), and predominantly white (82.5%), and non-Hispanic (92%). On univariable analysis (Table), high-volume centers had improved survival outcomes in the overall population, as well as in both SBRT and CRT subsets (p&lt;0.0001). On multivariable analysis, treatment during the most recent time period: 2016-2019 (HR 0.646, p&lt;0.001), receiving care at a high-volume center (HR 0.844, p&lt;0.001), use of SBRT (HR 0.915, p&lt;0.001), administration of multiagent chemotherapy (HR 0.706, p&lt;0.001) and undergone surgical resection (HR 0.405, p&lt;0.001) were associated with improved OS. In a subgroup analysis of patients receiving SBRT, median OS was 22.6 months for high-volume, 20.0 for intermediate-volume and 18.4 months at low-volume centers (p&lt;0.001). Conclusions: Patients receiving RT for LAPC or BRPC at high-volume centers had longer OS compared to those receiving radiation at intermediate- or low-volume centers. In those undergoing SBRT, treatment at high-volume centers had improved OS compared to intermediate- and low-volume centers. These findings suggest that radiation oncologists’ expertise is critical for providing high-quality RT in PC, especially for SBRT.[Table: see text]
Novel GPC3-targeting radiopharmaceutical therapy for hepatocellular carcinoma.
Authors: Fanching Lin, Renee Clift, Takeru Ehara, Hayato Yanagida, Steven Horton, Katrina Salvador, Samantha Richardson, Matt Guest, Alain Noncovich, Abhijit Bhat, Guangzhou Han, Ken Song, Jessica Rearden, Gary Li
Journal: Journal of Clinical Oncology (2024)

525 Background: Glypican-3 (GPC3) is a membrane-anchored oncofetal protein whose expression is largely absent in normal tissues. Significant upregulation of GPC3 protein has been observed in approximately 75% of hepatocellular carcinomas (HCC), and is associated with poor prognosis. The differential expression of GPC3 between tumor and normal tissues provides an opportunity for targeted radiopharmaceutical therapy (RPT) to treat HCC, a leading cause for cancer-related deaths worldwide. Methods: RAYZ-8009 comprises a novel macrocyclic peptide binder to GPC3, a linker, and a chelator that can be complexed with different radioisotopes. The affinity of peptide binders to GPC3 was determined by surface plasma resonance (SPR) and radioligand binding assays. Target-mediated cellular internalization was radiometrically measured at multiple time points. In vivo biodistribution, monotherapy and combination treatments with 177 Lu or 225 Ac were performed in HCC xenografts. Results: RAYZ-8009 showed high binding affinity (K D =0.7 nM) to human GPC3, with comparable affinity to GPC3 of human, mouse, canine and monkey origins, and no binding to other GPC family members. Potent cellular binding was confirmed in GPC3+ HepG2 cells, and was not affected by isotope switching. RAYZ-8009 achieved efficient internalization upon binding, with 42% internalized by 20 minutes in HepG2 cells. Biodistribution study of 177 Lu-RAYZ-8009 showed sustained tumor uptake and fast renal clearance, with minimal or no uptake in other normal tissues. Exquisite tumor-specific uptake was also demonstrated in orthotopic HCC tumors with no uptake in surrounding normal liver tissue. Therapeutically, significant and durable anti-tumor effect and survival benefit were achieved with 177 Lu- and 225 Ac-labeled RAYZ-8009, as monotherapy or in combination with lenvatinib, in GPC3+ HCC xenografts. Conclusions: Preclinical in vitro and in vivo data demonstrate the potential of RAYZ-8009 as a theranostic agent for the treatment of patients with GPC3+ HCC.
A phase I/II study of antroquinonol in combination with nab-paclitaxel and gemcitabine for patients with metastatic pancreatic cancer.
Authors: Yan-Shen Shan, Chung-Pin Li, Gazala Khan, Woo Jin Lee, Hye Jin Choi, Heung-Moon Chang, Moon Hee Lee, John M. Wallmark, Pei-Ni Chen
Journal: Journal of Clinical Oncology (2024)

648 Background: The survival of metastatic pancreatic cancer (mPC) is still disappointing though advancement in recent regimens. Antroquinonol, a new chemical entity, has been proposed for the treatment of neoplasms. In this phase I/II trial, we investigated the dose and efficacy of antroquinonol combined with gemcitabine and nab-paclitaxel (Gem/Nab-P) on mPC patients. Methods: Patients with chemo-naive, metastatic PDAC were enrolled. In the phase I, run-in drug-drug interaction (DDI) and dose escalation in a 3 + 3 designed to determine the maximal tolerated dose (MTD) of antroquinonol for phase II study. Gem/Nab-P (gemcitabine 1000 mg/m 2 and nab-paclitaxel 125 mg/m 2 on days 1, 8, and 15 every 4 weeks) was given from cycle 0 in phase I. The dose of antroquinonol was escalated from 200mg orally three times a day since the first cycle of Gem/Nab-P. The primary end points were median PFS and 6-month PFS rate. This trial is registered at ClinicalTrials.gov: NCT03310632. Results: In the phase I study of 15 patients, the MTD of antroquinonol was 300mg tid. In the phase II study of 40 patients, the median PFS was 5.3 (95% CI: 3.7–7.5) months and 6-month PFS rate was 40% (95% CI: 21%–57%), whereas median OS was 12.6 (95% CI: 8.8–15.8) months and12-month OS rate was 59.9% (95% CI: 37.8%–76.4%), respectively. The adverse events including hematological and non-hematological classes were decreased in the antroquinonol plus Gem/Nab-P, the GI discomforts were increased but manageable. Conclusions: In this phase I/II trial, antroquinonol plus Gem/Nab-P showed good efficacy in survival and less adverse events than a first-line strategy of Gem/Nab-P for mPC patients. Clinical trial information: NCT03310632 . [Table: see text]
A decade of chemotherapy management in hepatocellular carcinoma: A single-center study in Latin America.
Authors: Wagner Eduardo Cruz Diaz, Jackeline Macetas, Miriam Lazaro, Juan Carlos Carlos Haro Varas, Cristian Pacheco, Mónica Calderón Anticona, Jessica Diana Anampa Vargas, Mariana Serrano Cardoso, Victor Roman Paitan Amaro, Victor Castro Oliden, Paola Catherine Montenegro
Journal: Journal of Clinical Oncology (2024)

524 Background: Hepatocellular carcinoma (HC) is the most common primary tumor of the liver and is a significant health problem worldwide with check-point inhibitors and oral multikinase inhibitors (TKI) as the first-line therapy for advanced diseases. While chemotherapy treatment may not be standardized in current clinical management guidelines, it remains the only available treatment option in numerous Latin American countries. Methods: A retrospective review was carried out, in patients older than 18 years, between January 2011 and December 2020. 127 patients were analyzed and identified, they had received at least one course of chemotherapy at the Instituto Nacional de Enfermedades Neoplásicas in Lima, Perú. Results: The median age was 40 years, 40 female patients (31.5%) and 87 male patients (68.5%). Among the participants, 77 patients (60.62%) were diagnosed with hepatitis B, 2 patients (1.57%) had hepatitis C virus infections, and 48 patients didn´t have viral hepatitis. 72 patients (91.13%) underwent antiretroviral treatment. Non-cirrhotic patients were 118 (92.91%) and 111 (87.4%) had a Child A score. Chemotherapy was administered as first-line treatment to 118 patients (92.91%), with 47.61% receiving 5-FU-based chemotherapy, 11.11% Adriamycin, and 8.7% Gemcitabine-based chemotherapy. A smaller subset, consisting of 8 individuals (6.29%), received sorafenib as their first-line treatment. The overall survival (OS) rates at 12, 36, and 60 months were 74.14%, 20.69%, and 1.72%, respectively. Regarding disease-free survival (DFS) rates at 12, 24, and 48 months were 28.89%, 6.67%, and 2.22%, respectively. Conclusions: In this updated data for advanced hepatocellular carcinoma, we observed a subset of patients with advanced HC achieved favorable outcomes, with a median OS of 20.37 months and a median DFS of 6.6 months. Additional research is necessary to enhance our understanding of the molecular characteristics and resistance pathways of hepatocellular carcinoma in Peru and their correlation with the favorable survival rates observed in response to chemotherapy treatment.
Cell free DNA (cfDNA) assessment of esophagogastric (EG) cancer using MSK-ACCESS.
Authors: Samuel Louis Cytryn, William Phu, Ronak H. Shah, Henry S. Walch, Walid Khaled Chatila, Efsevia Vakiani, Angela Rose Brannon, Marc Ladanyi, Amitabh Srivastava, Laura H. Tang, Vivian E. Strong, Daniela Molena, David B. Solit, Michael F. Berger, Yelena Y. Janjigian
Journal: Journal of Clinical Oncology (2024)

406 Background: Treatment for EG cancer is increasingly complex and the role of predictive and prognostic biomarkers is critical in selecting the optimal therapy. Longitudinal, non-invasive methods that characterize dynamic molecular profiles and detect molecular residual disease are needed. Methods: Patients with EG cancer receiving care at Memorial Sloan Kettering (MSK) had cfDNA analysis with an ultrasensitive capture based liquid biopsy for detection of somatic alterations in 129 cancer associated genes (MSK ACCESS). Results: 98 patients with EG adenocarcinoma underwent cfDNA analysis; 18% had esophageal tumors, 44% had GEJ, and 38% had gastric. 78 (80%) patients had cfDNA obtained prior to treatment (48 [50%] metastatic; 29 [30%] locally advanced) and 21 (21%) at time of progression. 85% had matched tumor NGS performed with MSK IMPACT: median TMB was 5.3 mut/Mb (IQR 3.3-7.4) and median alterations per tumor sample was 11 (IQR 7-17). cfDNA identified a similar molecular profile compared to tumor NGS (TP53 [62 v 72%], ARID1A [12 v 20%], CDKN2A [10 v 16%], APC [10 v 13%], ATM [10 v 12%], PIK3CA [7 v 12%]), although cfDNA was detected more frequently in patients with metastatic disease compared to localized disease (p=0.02). cfDNA did not detect copy number alterations as frequently as patient-matched tumor NGS (41 v 16%, p&lt;0.01), including ERBB2amp (22 v 10%, p=0.05), though patients with HER2 IHC 3+ tumors were more likely to have detectable ERBB2amp on cfDNA compared to HER2 IHC 2+ tumors (50 v 9% p=0.03). Additionally, those with detectable ERBB2amp on cfDNA had a higher copy number on tumor NGS compared to those with undetectable cfDNA (median 39 [IQR 23-46] v 10 [IQR 6-15] p&lt;0.01). Baseline detection of ctDNA may indicate a poor prognosis; among patients with locally advanced disease (median follow up 20.1 months), 0 of 10 with undetectable ctDNA died compared to 5 (26%) of 19 with detectable ctDNA (p=0.08). Among patients with untreated, metastatic disease (median follow up 24.3 months), patients with undetectable ctDNA had a non-significant, improvement in PFS (HR 0.28 95% CI 0.08-1.17; p=0.08) and OS (HR 0.45 95% CI 0.10-1.96; p=0.20) compared to patients with detectable ctDNA, independent of disease burden. Conclusions: Our findings highlight the utility of cfDNA with MSK ACCESS as a complimentary tool for molecular characterization and potential prognostication in patients with EG cancer. [Table: see text]
De-risking 1st line chemotherapy-free immune checkpoint inhibitor (ICI) use for patients with advanced gastroesophageal cancer (aGEJ) with tumor mutational burden (TMB).
Authors: Samuel J. Klempner, Julia Quintanilha, Ali Aboosaiedi, Samantha Morley, Jerry W. Mitchell, Jeffrey S. Ross, Ryon Graf
Journal: Journal of Clinical Oncology (2024)

407 Background: ICI + chemotherapy (chemo-ICI) is becoming an increasingly common 1 st line regimen for patients with aGEJ. However, direct outcome comparison between biomarker-enriched groups receiving chemo-ICI vs. ICI monotherapy (mono-ICI) is limited in phase III trials. We sought to evaluate if TMB might identify patients for whom mono-ICI vs. chemo-ICI might be de-risked. We prospectively hypothesized that (1) patients with TMB &lt;10 mut/mB would have more favorable outcomes receiving ICI-chemo vs. mono-ICI and (2) patients with TMB ≥10 mut/mB would have diminished additional benefit from chemo-ICI vs. mono-ICI. Methods: This study included patients with aGEJ who received 1 st line chemo-ICI or mono-ICI and tumor tissue genomic profiling by Foundation Medicine. Patient data was obtained by the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine gastric real-world clinico-genomic database (FH-FMI CGDB), originating from approximately 280 US cancer clinics (January/2011–March/2023). Real-world progression-free survival (rwPFS) and overall survival (rwOS) were compared between patients receiving chemo-ICI vs. mono-ICI by Cox models, adjusted by propensity scores accounting for disease stage at diagnosis, ECOG PS, PD-L1 score and microsatellite instability (MSI) status. Comparisons of the explanatory power of TMB (&lt;10 vs. ≥10 mut/mB) vs. MSI status (MSI-H vs MSS) were performed by likelihood ratio test (LRT). Results: A total of 263 patients (176 receiving chemo-ICI and 87 mono-ICI) were included in the study. Patients with TMB &lt;10 mut/mB had more favorable outcomes receiving chemo-ICI vs. mono-ICI for rwPFS (median 5.8 vs. 1.9 months, hazard ratio [HR]: 0.44, 95% confidence interval [CI] 0.26-0.76), p=0.0029) and rwOS (median 11.1 vs. 7.9 months, HR: 0.68, 95% CI 0.40-1.15, p=0.1489). Patients with TMB ≥10 mut/mB did not have reduced benefit from mono-ICI; curiously less favorable outcomes were observed with chemo-ICI vs. mono-ICI for rwPFS (HR: 3.27, 95% CI 1.19-8.97, p=0.0212) and rwOS (HR: 3.56, 95% CI 1.14-11.08, p=0.0286). Evaluating only the mono-ICI group, the LRT indicated that when TMB was added to a model evaluating only MSI status, there was an improvement in ICI outcome prediction (p=0.006 for rwPFS and p=0.003 for rwOS), but not when MSI was added to TMB (p=0.91 for rwPFS and p=0.40 for rwOS). Conclusions: aGEJ patients with TMB &lt;10 mut/mB had more favorable outcomes receiving chemo-ICI vs. mono-ICI. In the TMB ≥10 mut/mB we did not observe more favorable outcomes among patients receiving chemo-ICI vs. mono-ICI. Curiously, we observed more favorable outcomes among those receiving mono-ICI in the TMB ≥10 mut/mB group. Among patients receiving mono-ICI, TMB better predicted mono-ICI outcomes compared to MSI status alone.