tbuckley/cabot-search huggingface dataset:
Mortality and equitability of radiation treatment in locally advanced rectal cancer: A review from a national cohort.
Authors: Joshua Walter Zweigle, Ahmed Hebishy, Srijan Valasapalli, Rana Mohamed, Mahvish Muzaffar, Aidan Michael Burke
Journal: Journal of Clinical Oncology (2024)

e15608 Background: The treatment paradigm for locally advanced rectal cancer has evolved significantly over the last two decades regarding the timing (neoadjuvant vs. adjuvant) and even the necessity of radiation (RT) or surgery in the curative approach. While these paradigm shifts were evolving, the overall survival (OS) of patients with and without RT and the inclusion of minority populations in these shifts has not previously been well described. Methods: A retrospective cohort study was performed using the NCI SEER database. Survival was calculated with IBM SPSS software using the Kaplan-Meier method and hazard ratios (HR) were calculated using the Cox-regression model with 95% confidence intervals (CI). Patients treated between 2000 – 2020 were included with the cause of death separating OS from cancer-specific survival (CSS). The 5-year survival after 2015 was unreliable and excluded. Patients were separated by whether they had received RT and by the timing of RT (neoadjuvant vs. adjuvant). Additionally, the patients were separated into ‘Non-Hispanic White’ (NHW) and ‘Other’. They were analyzed using a Chi-squared algorithm for an association between race and origin and receipt of RT. This same analysis was done on patients separated by race identified as ‘Black’ or ‘Not Black.’ These Chi-squared analyses were calculated for patients diagnosed before and after January 1, 2016. Results: Of those diagnosed with stage II or III rectal cancer from 2000-2015 who received chemotherapy and surgical intervention with known survival times, the receipt of RT, specifically neoadjuvant RT, improved OS and CSS. There was no evidence that NHW patients received RT at different rates from others. However, they did receive adjuvant RT at higher rates from 2000-2015 and neoadjuvant RT from 2016-2020. For Black patients, from 2000-2015 there was a trend towards lower rates of RT utilization and from 2016-2020 they were less likely to receive RT. Black race did not have a significant association with the timing of RT. Conclusions: Stage II and III rectal cancer patients diagnosed from 2000-2015 who received chemotherapy, surgery, and RT, specifically, neoadjuvant RT had improved OS and CSS. Black patients were less likely to receive RT and, as the standard of care was changing towards total neoadjuvant RT after 2015, NHW patients were more likely than others to be treated with this regimen. [Table: see text]
Short course versus long course neoadjuvant radiation for patients with locally advanced rectal cancer (LARC): National Cancer Database (NCDB) analysis of the years 2004-2020.
Authors: Gaurav Sharma, Gannon James Ray, Madhuri S Mulekar, Alexander Lund, Adam Huddleston, Amr M. Aref, Ahmed Abdalla
Journal: Journal of Clinical Oncology (2024)

e15606 Background: The two preoperative radiation approaches for LARC are long-course chemoradiotherapy (LC-CRT) and short-course radiation (SC-RT). While previous research suggested similar efficacy, the five-year follow-up of the RAPIDO trial revealed a significant increase in local recurrence rates with SC-RT. We aim to assess the outcomes and utilization patterns of both approaches in the United States of America (USA) using data NCDB. Methods: NCDB data for stage 2B, 2C, and 3 rectal cancer patients were obtained. SC-RT was defined as a total of 25 Gy in 5 fractions, and LC-CRT was defined as 45-60 Gy given over 5 to 6 weeks (with chemotherapy). Data was analyzed using JMP Pro V16. Results were considered significant at α = 0.05. Categorical data were compared using Fisher's or Chi-square test. Numerical data were compared using t-test or ANOVA. Post hoc analysis was conducted using Tukey's HSD. Survival rates were compared using the Kaplan-Meier method. Logistic regression was used to study outcomes' dependence on different factors. Firth adjusted maximum likelihood method was used to model likelihood of unstable outcomes due to biased estimates. Results: Out of the total 39,527 patients, 38,365 (97.06%) received LC-CRT, whereas only 1,162 (2.94%) received SC-RT. Only about 5% of patients received total radiation above 50.4 Gy. SC-RT was significantly more common among Hispanic patients (p = 0.0001), those with lower median income ( &lt; $30,000) (p = 0.01), individuals with more comorbidities (p &lt; 0.0001), and those treated at academic facilities (p &lt; 0.0001). In comparison to SC-RT, LC-CRT demonstrated lower 30 and 90-day mortality after surgery, a higher pathological complete response (pCR) rate, and improved overall survival (OS) (Table). Upon subgroup analysis by stage, significant OS improvement with LC-CRT compared to SC-RT for stage 3 (p = 0.02), whereas no difference in OS was found in stage 2B, C. Detailed analysis will be presented. Conclusions: SC-RT is used by less than 3% of US patients and mainly in academic centers. LC-CRT is more effective, improving pCR and OS. Favorable outcomes with LC-CRT may be due to poor baseline performance status in SC-RT group. Prospective trials are needed to validate these findings. [Table: see text]
Prognostic implications of distal resection margin length in rectal cancer proctectomy: A retrospective analysis.
Authors: Ming Li, Xiaodong Wang, Pengfei Niu, Yong Yang, Jiajia Chen, Jingxuan Xu, Yu Cheng, Yanzhao Wang, Chang Zhang
Journal: Journal of Clinical Oncology (2024)

e15605 Background: Proctectomy remains pivotal in rectal cancer treatment for 70% of patients, even post-neoadjuvant therapy. The determination of an appropriate distal resection margin (DRM) in proctectomy for rectal cancer is critical for achieving both curative resection and organ preservation. However, the prognostic impact of DRM length, especially measured before the shrinkage caused by fixation in pathology, remains unclear. Methods: This retrospective study include 224 stage II-III rectal cancer patients who underwent proctectomy between 2015 and 2020. Patient demographics, tumor characteristics, and follow-up data (median: 44.4 months) were collected. The lengths of mesorectal and rectal DRM were both measured on fresh specimens before pathological processing. A specific metric, (rectal DRM - mesorectum DRM)/rectal DRM &gt; 10%, identified patients with shorter mesorectal DRMs, denoted as the "MS group". Results: Out of 224 patients, 68 (30.4%) had a rectal DRM ≤1 cm, and 156 (69.6%) &gt; 1 cm. There were no significant differences between the groups in terms of gender, use of neoadjuvant therapy, or high-risk factors like extramural venous and perineural invasion. The local recurrence (LR), disease-specific survival (DSS) and overall survival (OS) rates did not differ significantly between groups, with P = 0.66, 0.082, 0.054, respectively. Cox univariate analysis identified pT, pN, gender, and CEA level as significant factors for OS and DSS, while DRM group was not (p = 0.06). A 5-year OS predictive model (AUC = 0.864) indicated DRM's insignificant impact on OS, validated against SEER and TCGA databases. Further analysis in 182 Dixon surgery cases revealed no significant OS or DSS differences between patients with mesorectal DRM &lt; 1cm and those with &gt; 1cm. Notably, 23.6% (43/182) belonged to the MS group with shorter mesorectal DRM, showing significantly inferior OS (P = 0.026) and DSS (P = 0.000265) compared to the ML group. Conclusions: In this study, while a 1 cm DRM in mesorectal and rectal regions is validated as safe for rectal cancer proctectomy, our findings indicate this is not an absolute measure of oncological safety. Patients with a mesorectal DRM shorter than the rectal DRM had inferior outcomes, suggesting the need for a more nuanced approach. Thus, a comprehensive DRM evaluation, beyond a fixed length threshold, is essential to improve surgical outcomes and patient prognosis.
Patient factors related to the real-world adoption of 3 months of adjuvant chemotherapy (ACT) in patients with stage III colorectal cancer (CRC).
Authors: Tharani Krishnan, Emily Leung, Joao Paulo Solar Vasconcelos, Howard J Lim, Jonathan M. Loree, Janine Marie Davies, Karamjit Gill, Sharlene Gill
Journal: Journal of Clinical Oncology (2024)

e15609 Background: Based on the IDEA analysis, 3 months (mos) of ACT with CAPOX is an option for both low-risk and high-risk stage III CRC, with potential resource utilization, cost and toxicity benefits. This study examined the patterns of uptake of CAPOX vs FOLFOX and duration of ACT, focussing on patient factors, in a contemporary post-COVID real-world cohort of patients (pts) in British Columbia, Canada. Methods: The provincial pharmacy database was used to identify pts with resected stage III CRC who received adjuvant CAPOX or FOLFOX from January 2021 to December 2022. Demographic, tumor, and treatment information was collected. Descriptive statistical analyses were performed to examine baseline characteristics and Fisher’s exact test was used to examine univariate associations. Results: 452 pts were included, of which 234 (52%) and 218 (48%) were planned to receive 3 and 6 mos of ACT respectively (see table). Within the 3 mos group, 226 (97%) received CAPOX. Within the 6 mos group, there was a 51%/49% split between CAPOX/FOLFOX. By univariate analysis, age &gt; 70y (P = 0.039), low/intermediate grade (P = 0.005) and low-risk disease (P &lt; 0.0001) were significantly associated with 3 mos of CAPOX. There was no difference in ACT choice with regards to ECOG status, ileostomy or pre-existing neuropathy. 29% of pts planned for 6 mos of ACT had low-risk disease, with 52% of these receiving CAPOX. Patients who received 6mos of ACT were significantly more likely to report neuropathy (68 vs 36%, P &lt; 0.0001) and to stop oxaliplatin early (54 vs 31%, P &lt; 0.0001). The most likely reason for early discontinuation of ACT was neuropathy in the 6mos group and gastrointestinal toxicity in the 3mos group (P &lt; 0.0001). Irrespective of duration, mean time from consult to ACT was longer for FOLFOX vs CAPOX (24 vs 19 days, P = 0.007). Conclusions: In this contemporary cohort, use of 3 mos of adjuvant CAPOX remains low. 6 mos of oxaliplatin is still being offered to pts with low-risk disease, and is associated with more neuropathy warranting early oxaliplatin cessation. Exploration of patient preferences and resource costs may improve more widespread adoption of 3 mos of adjuvant CAPOX in stage III CRC. [Table: see text]
First-in-class inhibitor of HSP110 blocks BCR activation through SYK phosphorylation in diffuse large B-cell lymphoma
Authors: Vincent Cabaud Gibouin, Manon Durand, Christophe Boudesco, François Hermetet, Kristyna Nozickova, Catherine Chassagne-Clement, Mayssa Abdelwahed, Pavel Klener, Carmen Garrido, Gaëtan Jego
Journal: Leukemia (2024)
MIRACLE1: Phase II study of radiotherapy followed by CapeOx and tirelizumab as first-line treatment in MSS rectal cancer with synchronous resectable liver/lung metastases.
Authors: Zezhi Shan, Menglong Zhou, Zilan Ye, Weijing He, Yufei Yang, Dakui Luo, Fan Xia, Lijun Shen, Yikuan Chen, Changming Zhou, Qingguo Li, Zhen Zhang, Xinxiang Li
Journal: Journal of Clinical Oncology (2024)

TPS3631 Background: Rectal cancer (RC) with synchronous resectable liver/lung metastases is commonly treated with surgery combined with systemic chemotherapy or local therapies. Prognosis remains poor. Microsatellite stable (MSS) are characterized by an immunosuppressive microenvironment and a low response rate to immunotherapy. Chemotherapy and Radiotherapy have been reported to potentially promote immunotherapy response. MIRACLE1 will investigate the safety and efficacy of Short-course radiotherapy (SCRT) combined with CapeOx and tirelizumab in MSS metastatic RC. Methods: We designed a single-arm, multicenter, phase II trial in MSS RC. MSS status is determined by normal immunohistochemical nuclear expression of all the mismatch repair genes MSH2, MSH6, MLH1 and PMS2. Additional inclusion criteria include RC with a distance of ≤ 10 cm from the anus by MRI evaluation and single or multiple measurable metastases in the liver and/or lungs (RECIST version 1.1) evaluated as resectable after MDT discussion. Exclusion criteria include patients with distant metastasis to parts other than the liver and lungs, including the brain, bone, ovary, peritoneum, and multiple retroperitoneal lymph node metastases.Patients are treated with radiotherapy including 25 Gy/5 fractions short-course hypofractionated radiotherapy (HFRT) for primary lesions and HFRT or stereotactic body radiotherapy (SBRT) for metastatic lesions. Afterward, six cycles of chemoimmunotherapy consisting of CapeOX and tislelizumab will be administered. Tislelizumab is administered intravenously (200 mg) along with each cycle of chemotherapy. Efficacy evaluations are conducted after the third and sixth cycles of chemoimmunotherapy and include radiological and serological evaluations. According to the efficacy evaluation results, a watch-and-wait nonoperative approach or surgical resection is performed. After surgery, postoperative treatment is to be determined by the investigators. Tislelizumab is to be maintained until one year after surgery. The primary endpoint of this study is the 1-year no-evidence of disease (NED) rate. The secondary endpoints include objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and acute toxicity related to immunotherapy. 52 patients will be enrolled to ensure 47 evaluable. The design has 80% power to detected improvement in NED rate from 60 to 77% with significance level of 0.05. The first patient was recruited on 27th March 2023. To date, 15 patients have been enrolled. Full accrual is anticipated by late 2024. Correlative studies include genomic characterization of baseline tumors, assessment of immune infiltration of tumor microenvironment and serial circulating cell-free DNA and immune biomarkers. Clinical trial information: NCT05359393 .
Randomized study to assess colonic microbiome changes in response to energy drink consumption (ROSANNA trial).
Authors: Tim Jang, Doga Kahramangil, Ji-Hyun Lee, George P. Kim, Sherise C. Rogers, Ilyas Sahin, Brian Hemendra Ramnaraign, Krista P. Terracina, Johan Nordenstam, Thomas Read, Ryan M. Thomas, Ye Yang, Christian Jobin, Thomas J. George
Journal: Journal of Clinical Oncology (2024)

TPS3630 Background: Colorectal cancer (CRC), the second leading cause of cancer deaths in the US, is increasingly diagnosed in individuals under 50. This rise in early-onset CRC (eoCRC) led the U.S. Preventative Services Task Force to recommend a reduction in the age to begin colorectal cancer screening in average-risk persons, from 50 to 45. The etiology of eoCRC is multifaceted, with one postulated theory pointing to alterations in the young adult colonic microbiome. Hydrogen sulfide (H 2 S) producing bacteria, like Bilophila wadsworthia, Fusobacterium nucleatum and Atopobium parvulum, are typically minor gut microbiota components but are overrepresented in CRC cases, linked to inflammation, and may promote a pro-carcinogenic environment. These bacteria preferentially use taurine, an essential amino acid, as a primary energy source. Energy drinks represent one of the largest dietary sources (6-16x normal daily intake) of taurine in contemporary diets. Our hypothesis is that high taurine levels in energy drinks could exacerbate CRC risk by promoting preferential growth and metabolic activities of already present H 2 S-producing bacteria, contributing to the rise of eoCRC. Methods: This randomized open-label trial is actively enrolling up to 60 young adults (18-40 years) without personal or family history of CRC, other major GI disease/distress, and baseline infrequent energy drink consumption. Group 1 (Arm A; n=30), will consist of subjects consuming at least one of two protocol-specified energy drinks daily for 4 weeks. Group 2 (Arm B; n=30), will consist of usual dietary intake. Enrollments are randomized 1:1 and stratified, by gender, age (18-25 vs. 26-40), and baseline energy drink consumption (rare/none vs. 1-2 per week). Every subject will complete: 1) a daily dietary and fitness log, 2) a weekly wellness log, 3) collection of stool/saliva/skin/urine at 3 sequential time points (baseline, after 2 weeks, after 4 weeks), and 4) blood collection at the same time points. The primary endpoint is the change in H 2 S-metabolizing bacterial communities between baseline and 1 month of energy drink exposure within Arm A and also compared to those in Arm B using microbiome analysis (diversity, taxonomy, sulfur-enriched gene pathways). Several secondary and exploratory assessments include changes related to subject demographic and dietary differences, concordance of microbiome changes with dietary logs and in other biospecimens beyond stool, H 2 S-production measurements, and analyses of subject metabolic and immune function. Trial opened in February 2024 with active enrollment ongoing. Updated data on trial status and any amendment modifications will be presented at the meeting. Clinical trial information: NCT06137248 .
Association of <i>BRCA1/2</i> pathogenic variants with primary tumor location and metastatic organotropism in pancreatic adenocarcinoma.
Authors: Ryan Hood, Srishti Rathore, Nicholas J. Seewald, Kim Anna Reiss
Journal: Journal of Clinical Oncology (2024)

4151 Background: Pancreatic cancers (PDACs) with BRCA1/2 pathogenic variants (PVs) are prognostically favorable and predict response to platinum-based treatment. Recent data suggest that these mutations may be more strongly associated with cancers arising from the body/tail (B/T) compared to the head of the pancreas (HOP). Primary tumors of the B/T are known to frequently metastasize to the peritoneum, which is thought to be largely due to anatomic location. We hypothesized that BRCA1/2 PVs may interact with tumor location in determining sites of metastatic spread. Methods: We conducted a retrospective study using a database of patients with BRCA1/2 PVs and PDAC as well as wildtype (WT) control patients matched for age, sex, year and stage at diagnosis. Demographic and clinical data were compared by Fisher’s exact test. Adjusted odds ratios for each site of metastasis or somatic variant were estimated using logistic regression with backwards stepwise AIC minimization. Cases with diagnosed metastases and available next generation somatic sequencing were included in the respective logistic regression models. Results: Patients with BRCA1/2 PVs were more likely to have masses in the B/T compared to control patients [51.6% vs 31.0%; p-value &lt; 0.001]. After adjusting for age, sex, platinum-based chemotherapy, curative-intent surgical resection, and primary location, patients with BRCA1/2 PVs were less likely to develop peritoneal metastases compared to control patients (see table, row 3). Additionally, for patients with B/T masses, the rate of peritoneal spread was significantly lower in those with BRCA1/2PVs compared to those without (OR: 0.41 [0.20, 0.83]). We did not observe a significant association between BRCA1/2 PV and peritoneal spread in patients with HOP masses (OR: 1.09 [0.48, 2.5]). Furthermore, patients with BR CA1/2PVs were significantly less likely to have a TP53 mutation compared to controls (51% vs 71%; p = 0.038). This association persisted after adjusting for the variables described above (see table, row 3). No significant differences were found for mutations in KRAS (83% vs 86%; p = 0.60), SMAD4 (16% vs 13%; p = 0.59), or CDKN2A (19% vs 29%; p = 0.13). Conclusions: Our data suggest that patients with BRCA1/2-related PDAC are more likely to present with B/T masses compared to WT patients, are less likely to have TP53 mutations and are less likely to have peritoneal spread of disease. These data support that the prognostic benefit of BRCA-related PDAC may be linked to a favorable somatic mutation profile. [Table: see text]
Atezolizumab + bevacizumab versus lenvatinib as first-line systemic therapy for treatment of hepatocellular carcinoma in a real-world population: Outcomes from the HCC CHORD database.
Authors: Mark Freeman, Tharani Krishnan, Cha Len LEE, Pooya Dibajnia, Ravi Ramjeesingh, Joao Paulo Solar Vasconcelos, Hanna Lyubetska, Philip Q. Ding, Howard J Lim, Jennifer J. Knox, Brandon M. Meyers, Vallerie Lynn Gordon, Winson Y. Cheung, Vincent C. Tam
Journal: Journal of Clinical Oncology (2024)

4111 Background: Lenvatinib (LEN) and the combination of atezolizumab with bevacizumab (AB) are widely considered first-line systemic therapies for the treatment of advanced hepatocellular carcinoma (HCC), but have never been compared directly in a randomized clinical trial. Cross-trial comparisons between IMbrave150 and LEAP-002 appear to show similar survival outcomes for AB compared to LEN, respectively, while survival with LEN was shorter in the REFLECT trial. Methods: Patients treated with AB or LEN first-line for HCC from August 2018 to August 2022 in the Canadian provinces of British Columbia, Alberta, Manitoba, Nova Scotia and two centers in Ontario were included in this study. Demographic and clinical outcomes data were gathered. Statistical analysis identified the median OS, PFS, and physician-assess response rate (RR) associated with each treatment. Results: We identified 453 patients treated with first-line AB (n = 159) or LEN (n = 294). 85% were male, 14% had HBV, 32% HCV, 70% cirrhosis, 27% BCLC B disease, 69% BCLC C,37% distant metastasis, 88% Child-Pugh A, 87% ECOG 0-1 performance status and 55% had previous locoregional treatment. The two cohorts were balanced with respect to most demographic factors, but patients in the LEN cohort had higher incidence of ECOG Performance Status ≥ 2 (11% vs 5%; p = 0.047), lower incidence of HBV (12% vs 19%; p=0.047) and higher incidence of HCV (36% vs 25%; p=0.03). Median follow-up time of the AB cohort was 9.9 months (mos) compared to 11.8 mos for LEN. Median overall survival (mOS) of this HCC population was 15.4 mos. mOS was 19.7 mos (95% CI: 14.5-NR) in the AB cohort and 14.4 mos (95% CI: 12.2-17.1) in the LEN cohort (HR 0.72; 95% CI: 0.54-0.95; p=0.021). Median progression-free survival (mPFS) was 6.9 mos in the overall population, 8.3 mos for AB and 6.3 mos for LEN (HR 0.85; 95% CI: 0.68-1.06; p=0.20). RR was 29% overall, 31% for AB and 28% for LEN (p=0.50). LEN was the most common second-line treatment after AB (86%), while after LEN 46% of patients received regorafenib and only 21% received second-line AB. Conclusions: This study provided real-world efficacy outcomes for AB directly compared to LEN in the first-line treatment of HCC in a Western country. AB was correlated with superior OS compared to LEN, but PFS and RR appear to be similar.