tbuckley/cabot-search huggingface dataset:
Neoadjuvant chemotherapy vs upfront resection: A challenging choice in resectable pancreatic ductal adenocarcinoma.
Authors: Fatemeh Fekrmandi, Brendan Hagerty, Qian Liu, Tyce Schneider, Nadia Malik, Christos Fountzilas, Moshim Kukar, Leonid Cherkassky, Benjamin Calvo
Journal: Journal of Clinical Oncology (2024)

620 Background: Pancreatic ductal adenocarcinoma (PDAC) remains an immense challenge within oncology, with only 15-20% of cases initially qualifying as resectable. Based on National Cancer Database analyses there is an increase in neoadjuvant chemotherapy (NACT) use, with potential downstaging effects. Yet, a subset of neoadjuvant-treated patients fail to proceed with curative-intent surgery, leading to worse outcomes. This retrospective analysis aims to uncover factors that predict NACT use and the impact on survival outcomes. Methods: A cohort of 543 consecutive non-metastatic PDAC patients treated at an NCCN-designated comprehensive cancer center between 2015 and 2022 were prospectively enrolled into a REDCap database. Based on NCCN resectability criteria, initial CT staging placed 96 patients as upfront resectable. Survival outcomes were compared using univariate and multivariate cox regression analyses. Results: Within 96 resectable patients, 45 (47%) underwent upfront surgery, 36 (37%) received NACT followed by surgery and 15 (16%) only received chemotherapy. The majority were CA19-9 secretors (94%) with 54% lower values during chemotherapy. While 60% of patients experienced up to 35% tumor size reductions on NACT, 20% had stable disease, and 20% showed progressive disease. The patients who received NACT were significantly younger (p = 0.01), with higher baseline CA19-9 (p &lt; 0.01) and more frequently underwent stent placement (p = 0.01), table 1. Median overall survival for the upfront surgery, NACT+surgery and chemotherapy groups were 32.8, 23.7 and 20.2 months (log-rank test p&lt;0.01) subsequently. On univariate analysis initial presentation with weight loss (p = 0.02, HR = 2.08) and high baseline CA19-9 (log2-scaled, p = 0.01, HR = 1.13) were predictive of worse overall survival. After adjusting for potential confounding variables, patients in chemotherapy group had significantly worse survival compared to the upfront surgery group (P &lt; 0.01, HR = 3.14). These 15 patients failed to undergo surgery due to diverse reasons, including distant progression (7), local progression (3), performance status decline or death during chemotherapy (2), refusal due to chemotherapy side effects (2), and indecision and loss to follow-up (1). Conclusions: These findings underscore the need for more robust selection criteria in resectable PDAC patients to undergo NACT. Leveraging real-world data helps identify predictive factors of treatment decision making and their impact on patient survival outcomes. [Table: see text]
Associations between BMI, morphomics and survival in 528 patients with metastatic pancreatic cancer.
Authors: Valerie Gunchick, Edward Brown, Stewart Wang, Grace Su, Vaibhav Sahai
Journal: Journal of Clinical Oncology (2024)

637 Background: Literature describing associations between patient body mass index (BMI) and survival in pancreatic ductal adenocarcinoma (PDA) remains inconsistent. This heterogeneity may be due to studies using pre-diagnosis BMI and including few metastatic patients despite high prevalence at diagnosis. Furthermore, BMI may not adequately reflect other body compositions such as those reflected via morphomic variables (subcutaneous fat, visceral fat, muscle, and fascia) that may have unique associations with survival. In this study, we sought to explore the relationships between detailed body composition in patients with metastatic PDA on both overall survival (OS) and progression-free survival (PFS). Methods: We evaluated data and scans from a phase 3 clinical trial in which 528 patients with metastatic PDA with no prior chemotherapy were randomized to either FOLFIRINOX or modified FOLFIRINOX plus devimistat. No differences in response rate, median PFS or OS were observed. Of the 528 enrolled patients, 377 had baseline CT scans eligible for morphomic evaluation for which Analytic Morphomics was used to measure body composition. For analysis, morphomic variables were summed across the T10-T12 and L1-L4 vertebrae and then divided into tertiles. BMI at diagnosis was evaluated in tertiles and per WHO standards. Cox proportional hazards models and cubic splines were used to evaluate associations between BMI, morphomic variables and PFS, OS. Univariate and multivariate models were evaluated. Kaplan-Meier plots were created to evaluate median survival times between those in the highest and lowest tertiles (R v4.3.1). Results: We did not observe an association between BMI and PDA patient survival: HR (95% CI) comparing BMI ≥30 (obese) to 18.5-24.9 (healthy weight), PFS 0.96 (0.66, 1.39), p-trend=0.80; OS 0.87 (0.64, 1.18), p-trend=0.30. However, multiple morphomic variables were significantly associated with PFS and/or OS in univariate and multivariate models when comparing the highest to lowest tertile. More subcutaneous fat was associated with longer median OS (12.4 vs 10.5 mos, p=0.006; HR (95% CI) 0.41 (0.25-0.68), p-trend=0.001). More dense visceral fat was associated with shorter median PFS (6.0 vs 9.1 mos, p=0.05, HR (95% CI) 1.52 (1.00-2.33), p-trend=0.047). A higher muscle to fascia ratio was associated with longer PFS (9.3 vs 6.5 mos, p=0.03; HR (95% CI) 0.58 (0.38-0.88), p-trend=0.01) and median OS (13.9 vs 10 mos, p=0.005; HR (95% CI) 0.53 (0.38-0.76), p-trend=0.0004). Conclusions: BMI was not associated with PFS or OS in this large prospective study of patients with metastatic PDA receiving chemotherapy. However, morphomic variables including subcutaneous fat area, visceral fat density, and the muscle to fascia ratio were statistically significantly associated with metastatic PDA patient survival.
Adjuvant TACE plus lenvatinib as compared with TACE alone in patients with hepatocellular carcinoma at high risk of recurrence after surgery: A prospective controlled study.
Authors: Bin Zhang, Renan Jin, Junjie Xu, Ming yu Chen, Jiang Chen, Hepan Zhu, Jiasheng Cao, Chao Song, Zaibo Yang, Yewei Zhang, Xiao Liang
Journal: Journal of Clinical Oncology (2024)

505 Background: Hepatocellular carcinoma (HCC) remains the fourth leading cause of cancer related deaths globally. Radical resection is still the main curative approach for patients with resectable HCC in China. However, the high 5-year postoperative recurrence rate of about 40% to 70% had become the main negative factor affecting the long-term survival benefit. Although transarterial chemoembolisation (TACE) can effectively reduce the recurrence rate and improve disease-free survival (DFS) and overall survival (OS), the outcomes of patients at high risk of recurrence are still not satisfactory. Thus, there is an urgent need for new adjuvant treatment regimen to further improve the survival outcomes. In this study, we compared the efficacy and safety of the lenvatinib plus TACE with TACE alone for postoperative patients with HCC who were at high risk of recurrence. Methods: The factors associated with high risk of recurrence were defined as pathological suggested vascular invasion (including vascular embolus, cholangiocarcinoma embolus and microvascular invasion), suspicious positive surgical margin or surgical margin &lt; 1cm, satellite lesion with cancer, positive lymph nodes, low differentiation and incomplete envelope. Eligible patients were those who had received radical resection for HCC and had risk factors above. Patients were assigned in a 1:1 ratio to receive the combination of lenvatinib and TACE or TACE alone. Results: From September 2019 to May 2023, 119 patients were enrolled in Sir Run Run Shaw Hospital, Zhejiang University School of Medicine. Sixty received TACE + lenvatinib and 59 received TACE only. The baseline characteristics were similar between two groups. The median duration of follow-up was 22.5 months (rang: 3 to 47) in TACE + lenvatinib group and 23 months (rang: 5 to 48) in TACE group. The 1-year DFS rate was 81.2% (95% CI: 70.8%-93.1%) in lenvatinib + TACE group, which was significantly higher than that of TACE group (58.3% [95% CI: 46.8%-72.7%], p = 0.0087; HR = 0.44 [95% CI: 0.23-0.83]). The median DFS was not reached (95% CI: 28-NR) in lenvatinib + TACE group, and was 20.0 months (95% CI: 12.0-NR) in TACE group. Patients' liver function after treatment with TACE + lenvatinib was comparable to that in the baseline. Conclusions: The preliminary results of this study suggested that adjuvant lenvatinib in combination with TACE can significantly improve DFS compared with TACE alone in patients with HCC at high risk of recurrence after surgery. The toxicity of combined treatment was tolerable and manageable. The follow up is still ongoing to observe the long-term benefit of this treatment regimen.
Intra-operative radiation for pancreatic cancer: Initial experience at the Hadassah Medical Center.
Authors: Gianella Cornejo, Philip Blumenfeld, Ayala Hubert
Journal: Journal of Clinical Oncology (2024)

634 Background: Prognosis following surgery for pancreatic cancer (PC) remains poor. Local recurrence is common and negatively impacts survival rate. In an effort to improve local control and potentially improve survival, we have adopted a strategy of adding intra-operative electron radiation therapy (IOeRT) to selected patients undergoing pancreatic resection (PR) for PC. Here we report our initial experience with this treatment modality. Methods: 14 patients (10 male, 4 female), age between 44 - 81 years (mean 66.17), who underwent PR (Head 7, Body7) between 1/2021-1/2023 were included in this analysis. Patients selected for IOeRT included patients that according to surgeon assessment were at risk not to achieve satisfactory resection margins by surgery alone. All had resectable or borderline resectable disease according to standard criteria. 8 patients underwent pre-op chemotherapy followed by stereotactic body radiotherapy (SBRT) to a dose of 25-40 Gy in 5 fractions to the tumor and regional lymphatics followed by PR (5 Whipple, 3 distal pancreatectomy) and IOeRT, 3 patients received preop SBRT followed by PR (3 distal pancreatectomy) + IOeRT, 2 patients underwent PR (whipple 1, distal pancreatectomy 1) + IoeRT, and 1 received neoadjuvant chemotherapy followed by SBRT only and did not undergo surgery due to tumor progression. Immediately following resection, mobile IOeRT accelerator using a 40-80mm applicator with a level of 0-15 degrees was directed at the tumor bed deemed at high risk for recurrence. 10-20 Gy was delivered using 6-8 MeV electrons to the 90% isodose line at the discretion of the treating radiation oncologist. Data including serial imaging, genomic analysis, radiation protocol, complications, pathological results and outcome was collected for analysis. Results: Mean follow up was 9.7 months (2-21). 8 patients are alive: 7 pts with no evidence of disease and 1 pt with liver metastases. 6 patients died: 4 with distant metastatic disease, 1 from disease progression prior to surgery and 1 from early post-op sepsis. Negative surgical margins were achieved in 10 patients of which 2 mutated BRCA gene carriers showed complete pathological response (both who received combined neoadjuvant chemotherapy followed by SBRT). Post-operative complications possibly attributed to RT included hepatic artery occlusion (1 pt), portal vein stenosis (1 pt) and prolonged GI tract dysfunction (1pt). Conclusions: Combining RT with resection appears feasible and safe. Our data possibly show a reduction in local recurrence following resection of PC, however, longer follow up is necessary. Refinements in patient selection and treatment protocol may further improve outcomes. Larger scale studies are required to determine the benefit of this modality.
Real-world analyses of BRAF alterations in patients with non-colorectal gastrointestinal cancers.
Authors: Amit Mahipal, Emily Teslow, Ellen B. Jaeger, Melissa Conrad Stoppler, Zhaohui Jin, AMR MOHAMED, Melissa Amy Lumish, Madison Conces, Sakti Chakrabarti
Journal: Journal of Clinical Oncology (2024)

759 Background: BRAF V600E mutations are present in 5-10% of patients with advanced colorectal cancer (CRC) and associated with poor prognosis. Recently, there was tumor agnostic FDA approval of dabrafenib + trametinib for BRAF V600E mutated solid tumors. However, the frequency of BRAF alterations ( BRAF alt), especially non-V600E, in other gastrointestinal (GI) cancers are not well described. This study characterizes BRAF alt in CRC vs other GI cancers (non-CRC). Methods: De-identified records from 51,560 patients diagnosed with GI cancers were retrospectively analyzed from the Tempus database. The molecular landscape including presence of pathogenic/likely pathogenic BRAF alt was evaluated by panel-based tissue DNA, RNA or ctDNA NGS sequencing (Tempus Labs, Inc.). The frequency of BRAF alt, co-mutations, MSI, TMB and MMR were compared between CRC and (non-CRC) by Chi-squared/Fisher’s Exact or Wilcoxon rank-sum tests. False-discovery rate correction was used for multiple testing. Results: BRAF alt were identified in 8.9% of CRC and 2.2% of non-CRC cohort. BRAF alt frequency varied by tumor type with the highest observed in colon (11%), jejunum (9.6%), intrahepatic bile duct (5.3%), rectal (4.5%), and ampulla of vater (4.5%) and lower in esophageal (0.9%) and gastric (1.6%). BRAF alt CRC had higher frequency of females (57% vs 45%, p &lt;0.001) and older age at diagnosis (67 vs 66 yrs, p=0.029) compared to non-CRC group. Race was also significantly different, with white patients being more predominant in both groups (85% CRC,77% non-CRC). Among the BRAF alt, fusions (12% vs 2.2%, p &lt;0.001) and amplifications (3.1% vs 0.3%, p &lt;0.001) were higher in non-CRC vs CRC (Table). BRAF V600E was most common in all GI tumors, but higher in CRC vs non-CRC (75% vs 27%, q&lt;0.001). Mutations higher in non-CRC vs CRC (q&lt;0.009) included class II (G469A, K601E, BRAF-SND1, and BRAF amplification) and class III (D594N &amp; N581S) BRAF alt. BRAF co-occurring mutations in CRC were TP53 (70%), APC (42%), RNF43 (30%), SMAD4 (22%), and PIK3CA (21%), and in non-CRC: TP53 (52%), CDKN2A (32%), CDKN2B (20%) SMAD4 (17%) and MTAP (16%). Among tissue samples, MSI-H (30% vs 4.%, p &lt;0.001) and TMB-H ≥10 mut/MB (32% vs 6.7%, p &lt;0.001) were more frequent in BRAF alt CRC vs non-CRC. Conclusions: Meaningful differences were found between the groups in terms of demographics, frequency, and type of BRAF alt and co-occurring mutations. In particular, certain BRAF fusions were present in a higher proportion of other GI cancers and could be an important therapeutic target for this patient population.[Table: see text]
Comprehensive genomic profiling of squamous cell carcinoma of unknown primary presenting with liver metastases.
Authors: Hannah Ruth Robinson, S. Lindsey Davis, Dean C. Pavlick, Karthikeyan Murugesan, Katy Ann Wong, Elaine T. Lam, Jeffrey S. Ross, Christopher Hanyoung Lieu
Journal: Journal of Clinical Oncology (2024)

755 Background: Carcinomas of unknown primary (CUPs) are comprised of metastatic cancers for which a primary tumor of origin cannot be identified despite a full diagnostic workup. They frequently present with liver metastases, which portend a poor prognosis. Strategies employing comprehensive genomic profiling (CGP) to identify targeted treatments for CUPs have shown potential. Despite this, the molecular landscape of squamous cell carcinomas of unknown primary (SCCUPs) remains poorly defined. This study describes the results of CGP testing in patients with SCCUPs identified in the Foundation Medicine, Inc. database, with a focus on those with liver involvement. Methods: Cases of SCCUPs with FoundationOne CDx (F1CDx) assay results were identified based on a reported diagnosis of CUP and the presence of SCC histology. Cases then underwent central pathologist review and were excluded if a known primary site could be determined based on histology and disease location. Cases with liver involvement were selected based on the site of tissue biopsy. Genomic analyses of identified cases were assessed using the FoundationCORE database. Results: Sixty-nine cases of SCCUP presenting with liver involvement were identified. Alterations were observed in 102 of 324 (31.5%) genes evaluated by the F1CDx assay in at least 1 patient. The most frequently altered genes were TP53 (66.7%) , CDKN2A (33.3%) , CDKN2B (23.2%) , KRAS (21.7%; 0% G12C) , PIK3CA (18.8%), NFE2L2 (11.6%), SOX2 (11.6%), M2M2 (10.1%), and MTAP (10.1%). No patients had microsatellite instability-high disease, only 6 (8.7%) patients had a tumor mutational burden (TMB) ≥ 10, and 11 (15.9%) patients had evidence of HPV infection. Among 33 patients with available PDL-1 testing results, 7 (21.2%) had high-positive expression. An additional 374 cases of SCCUP were identified with involvement outside of the liver. Compared to these cases, patients presenting with liver involvement had less genomic alterations per tumor (5.10 vs 6.71, p=0.005), and were less likely to have TMB ≥ 10 (8.7% vs 38.0%; odds ratio [OR] 0.16, p&lt;0.001). KRAS mutations were observed in 21.7% of those presenting with liver metastases compared to 8.3% of other SCCUP patients (OR 3.07, p=0.07). Conclusions: SCCUPs presenting with liver metastases had reduced numbers of genomic alterations and decreased TMB compared to other SCCUPs, suggesting these tumors may be less likely to respond to immunotherapy. Despite this, 36.2% of these patients had at least one alteration that could potentially guide targeted treatment decisions including entry into biomarker-driven clinical trials. Interestingly, there was a trend toward increased KRAS alterations in those with liver metastases. To our knowledge, this is the first report that describes the genomic landscape of SCCUPs presenting with liver metastases.
Patterns of surgery and adjuvant therapy in pancreatic carcinoid tumor: An NCDB analysis.
Authors: Connor Lanoue, Marco Braaten, Christopher Reese Bine, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2024)

631 Background: Pancreatic Carcinoid Tumor (PCT) is a neuroendocrine tumor (NET) of the gastrointestinal (GI) tract composed of Argentaffin cells. Of the primary pancreatic cancers, NETs are exceedingly rare in comparison to pancreatic adenocarcinoma, accounting for less than 2% of pancreatic cancer diagnoses. PCTs constitute for only a subset of these and hold a better prognosis than adenocarcinoma (What Is a Pancreatic Neuroendocrine Tumor? | American Cancer Society, n.d.). GI carcinoid tumors classically originate in the appendix, ileum, or rectum, and are seldom a primary neoplasm of the pancreas. PCTs generate secretory products with Serotonin being the most frequently isolated. Some cases may produce a carcinoid syndrome with characteristic diarrhea, cutaneous flushing, and bronchospasm (Ha &amp; Tan, 2012). Surgical resection is the hallmark of treatment, though other modalities of management are available. Due to the rarity of PCT, no significant study exists in the literature analyzing the association of survival with receipt of surgery or predictors of receipt of surgery. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with PCT from 2004 to 2019 using the histology codes 8240 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, Binary Logistic Regression and Cox Proportional Hazards tests were performed. Data was analyzed using SPSS version 29 and statistical significance was set at α = 0.05. Results: 2237 patients with PCT formed the final sample, with an average age of 61 years of age. 724 patients (32.3%) underwent surgery of the primary site, 72 (3.2%) received adjuvant chemotherapy, and 9 (0.4%) received adjuvant radiation. Surgery alone was associated with the longest median survival ( 198.5 months) compared to the other treatments ( Adjuvant chemotherapy=155.3 months, Adjuvant radiation=122.7 months, No surgery=73.95 months; p&lt;0.05). After controlling for covariates, receipt of surgery was independently associated with decreased overall mortality ( HR=.380; p&lt;0.05). Decreased age, lower grade tumors, and fewer positive regional lymph nodes were significantly associated with increased odds of receiving surgery. Additionally, treatment at an academic facility and private insurance status was associated with significantly higher rates of surgery. Patients who did not receive surgery were significantly older, had later stage disease, higher co-morbidity scores, and larger tumor size. Income level and race had no effect on treatment selection. Conclusions: This study found that surgery alone without adjuvant therapy is independently associated with improved survival. Favorable clinical characteristics may be contributing to this discrepancy in survival. Further exploration of treatment strategies in PCT may benefit patients through the creation of definitive treatment guidelines to manage this disease.
Role of proton pump inhibitors in immune checkpoint inhibitor colitis.
Authors: Roshini Pradeep, Afsheen Moshtaghi, Hamza Khan, Ann K Walenga, Neychelle Rocca, Andrzej Piotr Kudelka
Journal: Journal of Clinical Oncology (2024)

743 Background: Proton pump inhibitors (PPIs) are known to be beneficial in symptomatic control of gastroesophageal reflux disease and gastritis which can be a common complication of various cancers specifically gastrointestinal (GI) cancers. Microscopic colitis development has been studied to be associated with PPI use. Immune checkpoint Inhibitor (ICI) colitis is a known adverse effect of Inhibitors of Programmed cell death 1 (PD-1) and its ligand (PD-L1). Previous studies have also shown use of PPIs and NSAIDs are common risk factors which can exacerbate ICI Colitis caused by Inhibitors of PD-1 and PD-L1. This study is designed to observe association of certain drugs especially PPIs in ICI colitis. Methods: This is a single center, retrospective, and observational study that investigated patients treated with PD-1 and PD-L1 Inhibitors for management of any type of cancer between January 2022- September 2023. A list of patients treated with PD-1 and PD-L1 inhibitors was obtained from Inpatient pharmacy records followed by retrospective chart review to look for symptoms of colitis and other medications used by each patient. Primary outcome was to observe the role of PPIs in ICI colitis. Secondary outcomes were to observe the number of patients with GI cancers on PPIs who developed colitis. We also observed the effect of NSAIDs use as a potential risk factor in the population with ICI colitis. Results: The data consisted of 93 patients of which 17 (18.3%) developed colitis. Among this population 13 (76.5%) was ICI colitis, 2 (11.7%) was diverticular colitis and 2 (11.7%) was Infectious colitis. PPI use was seen in 3 out of 13 patients (23%) with ICI colitis. Patients with any type of GI cancer who developed colitis was 5 (25%) and PPI use in ICI colitis was seen in 2 out of these 5 patients. NSAIDs use was seen in 3 (23%) patients with ICI colitis. Conclusions: We did not observe significant association between PPI use and ICI colitis. ICI use becoming increasingly common in oncologic population, larger studies may be needed to further evaluate risk factors associated with ICI colitis in this population.