tbuckley/cabot-search huggingface dataset:
Stereotactic body radiotherapy compared to conventionally fractionated radiotherapy for locally advanced or oligometastatic pancreatic cancer.
Authors: Ofri Mizrahi, Tal Falick Michaeli, Ayala Hubert, Marc R. Wygoda, Philip Blumenfeld
Journal: Journal of Clinical Oncology (2024)

677 Background: Pancreatic cancer, particularly in its locally advanced and oligometastatic forms, poses a formidable therapeutic challenge. Radiotherapy remains an important treatment in an attempt to gain local control, however there is no consensus on whether stereotactic body radiotherapy (SBRT) is appropriate as compared to conventionally fractionated radiotherapy (CFRT). Herein, we report our experience. Methods: We conducted a retrospective analysis of patients with locally advanced and oligometastatic pancreatic cancer who received definitive radiotherapy at our institution between January 2010 and March 2023 with SBRT 30-50 Gy in 3-5 fractions or CFRT 50-60 Gy in 25-30 fractions. We excluded all patients with resectable disease who underwent surgery. Clinicopathological data, treatment regimens, and radiation parameters were collected and analyzed. Results: A total of 51 patients (17 females, 34 males; median age: 67.9 years). 24 patients (47.1%) were treated with CFRT, and 27 patients (52.9%) were treated with SBRT. Median time of follow-up for the entire cohort was 14.4 months. A total of 13 patients (25%) experienced a Local failure (LF) at a median time of 18.5 months, with no difference observed between CFRT and SBRT groups. Cancer-specific mortality (CSM) was statistically significant with a lower mortality rate in SBRT (37%) vs CFRT group (63%) (p&lt;0.004). Several treatment characteristics and dosimetric factors such as sex, age, receipt of chemotherapy, type of chemotherapy, use of elective nodal irradiation, GTV size, biologically equivalent dose (BED) corrected prescribed dose, minimum dose to GTV, or max dose to GTV did not predict local failure. There was no difference in QOL and toxicity between the two groups. Conclusions: In our cohort, local failure rates remain high and were similar between patients treated with SBRT compared to those treated with conventionally fractionated radiotherapy. We were unable to identify any specific predictors for local recurrence in this patient population. Our observation of a lower CSM rate among patients who received SBRT needs further study. The findings underscore the need to further improve radiotherapeutic approaches in an attempt to improve local control in locally advanced disease.
Multiomic analysis for minimal residual disease detection: Addressing challenges in stage II-III colon cancer from COSMOS-CRC-01.
Authors: Yoshiaki Nakamura, Yuichiro Tsukada, Nobuhisa Matsuhashi, Tatsuro Murano, Manabu Shiozawa, Takeshi Kato, Eiji Oki, Masahiro Goto, Yoshinori Kagawa, Akiyoshi Kanazawa, Takashi Ohta, Akira Ouchi, Hideaki Bando, Hiroshi Uchigata, Chiemi Notake, Mingyang Cai, Shile Zhang, Thereasa A. Rich, Kimberly Banks, Takayuki Yoshino
Journal: Journal of Clinical Oncology (2024)

180 Background: A considerable number of patients with stage II-III colon cancer experience disease recurrence following definitive treatment while others may receive unnecessary toxicity from adjuvant chemotherapy. Minimal residual disease (MRD) detection through ctDNA analysis can be evaluated without reliance on tissue which comes with logistic advantages and may be the only option for patients with limited tumor specimens. Methods: COSMOS-CRC-01 is an ongoing biomarker study that enrolled patients with resectable stage 0-III colorectal cancer between January 2020 and April 2021. Plasma samples and clinical data were collected 28 days post-operatively and every 3-6 months for up to 5 years alongside radiographic imaging. Samples were tested on the Guardant Reveal Infinity Oncology Platform for MRD detection. This analytically validated multiomic NGS assay interrogates &gt;700 genes and ~15Mb of methylated regions. A bioinformatics algorithm trained for CRC detection classifies each sample as ctDNA detectable or undetectable based on a predefined statistical likelihood threshold and returns quantitative tumor fraction. The primary endpoint was time to recurrence (TTR) based on ctDNA detection status. Results: This subgroup analysis evaluated 801 post-surgical plasma samples (4mL each, median input 19ng, 96% passed QC) from 136 patients with R0 resected stage II-III colon cancer with a median follow-up of 28 months. ctDNA detection at Day 28 post-surgery and following adjuvant chemotherapy were both associated with significantly shorter TTR (p&lt;0.0001; Table). Sensitivity with serial measurement was 80% (95% CI, 56.3-94.3%), with a median lead time of 5.3 months. Sensitivity was highest for detection of locoregional (2/2), brain (1/1), liver (7/7), or multiple (3/3) metastasis compared to isolated lung (2/4) or peritoneal (1/3) metastasis. Tumor fraction increased as expected in samples collected closer to the time of radiographic detection. Three recurred patients had KRAS G12C variants detected in ctDNA prior to recurrence, suggesting the potential of early intervention with targeted agents. Among 553 post-treatment samples from 114 non-recurred patients, sample specificity was 97.3% (95% CI 95.6-98.5%). Conclusions: We show a plasma-only genomic- and methylation-based assay to have sensitive and specific detection of MRD in stage II-III colon cancer. Serial measurement provides superior performance versus one-time measurement at Day 28 post-surgery and detects targetable variants prior to recurrence. [Table: see text]
Health Care Contact Days Among Older Adults in Traditional Medicare
Authors: Ishani Ganguli, Emma D. Chant, E. John Orav, Ateev Mehrotra, Christine S. Ritchie
Journal: Annals of Internal Medicine (2024)

Days spent obtaining health care outside the home can represent not only access to needed care but also substantial time, effort, and cost, especially for older adults and their care partners. Yet, these "health care contact days" have not been characterized.
Survival by race and ethnicity among insured patients with early-onset colorectal cancer.
Authors: Jeffrey Lee, Christopher Jensen, James Kang, Jessica Badalov, Theodore R. Levin, Kevin Kane, Amie Tan, Norelle Reilly, Sheena Gurai, Natalia Udaltsova, Douglas Corley
Journal: Journal of Clinical Oncology (2024)

18 Background: Colorectal cancer (CRC) incidence and mortality have decreased in the United States over the past 3 decades, but the incidence is increasing in those &lt;50 years of age (i.e., early-onset CRC). Studies have examined racial and ethnic differences in CRC incidence in this age group, but little is known about differences in survival. Examining survival by race and ethnicity among patients with early-onset CRC may provide insights about differences in risk factors, access to care, and treatment. Methods: This retrospective cohort study included Kaiser Permanente Northern California health plan members 18-49 years of age and diagnosed with CRC between 2006-2019. Race and ethnicity were self-reported as Asian/Pacific Islander, Black, Hispanic, or White. 5-year survival probability was assessed using Kaplan-Meier analyses. Cox regression with adjustment was used to evaluate associations between race and ethnicity and 5-year survival. Results: Of 1620 patients, median age was 45.4 years, 47% were female, 20% were Asian/Pacific Islander, 8% Black, 22% Hispanic, and 50% non-Hispanic White persons. Adjusted for age, sex, and comorbidities, Hispanic persons had a higher risk of death at 5 years compared to White persons (hazard ratio [HR]: 1.41; 95% confidence interval [CI]: 1.09-1.83) (Table). Sequentially adding annual household income and neighborhood deprivation index had no impact on the association; adding tumor stage decreased the HR to 1.14 (0.87-1.49) and adding tumor and treatment factors decreased the HR to 1.08 (0.82-1.42). Risk of death among Asian/Pacific Islander and Black patients did not differ from White patients. Conclusions: Among insured patients with early-onset CRC, Hispanic patients had a higher risk of death at 5 years than patients of White race. The higher risk was associated with differences in tumor stage at diagnosis, tumor factors, and treatment factors. Targeted interventions to improve CRC symptom awareness and remove barriers to CRC diagnosis and treatment among vulnerable populations may be needed to eliminate disparities in early-onset CRC survival. [Table: see text]
Income and its impact on adenomatous neoplasms outcomes: An analysis of the National Cancer Database.
Authors: Eric G. Nielsen, Christopher Reese Bine, Aron Lee, Alec Czaplicki, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2024)

723 Background: Adenomatous neoplasmsof the small intestine are rare benign tumors but are occurring with increasing incidence. They exhibit a slight male predominance, with a median age of diagnosis in the 6th decade of life. The duodenum is the most frequent location of onset. Proposed environmental risk factors include high animal fat and protein diets, intestinal flora composition, and hereditary factors. Additionally, intestinal diseases, such as Crohn’s disease or Lynch syndrome, predispose individuals to develop small intestine adenomatous neoplasms. Despite this knowledge, no National Cancer Database (NCDB) research exists analyzing the association between survivability and income. Therefore, the objective of this study is to investigate overall survival rates among individuals with adenomatous neoplasms based on income levels. Methods: The NCDB was used to identify patients diagnosed with small intestine adenomatous neoplasms from 2004 to 2019 using the histology code 8140 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square tests were performed, and data were analyzed using SPSS version 27. Statistical significance was set at α = 0.05. Results: Of 19,582 patients included in the sample, 6,326 (30.8%) were from the highest income bracket, defined as annual income greater than $46,000, while 3,629 (24.4%) were from low-income brackets, defined as earnings less than $30,000. High-income patients experienced longer mean overall survival (58.5 months) compared to middle (49.7 months) and low (46.7 months) income patients (p&lt;0.001). After controlling for age at diagnosis, sex, race, facility type, surgery status, adjunctive therapies, and insurance type, both the low- and middle-income brackets were associated with an independent increase in hazard (HR = 1.284 and 1.177 respectively; p&lt;0.001). High income was associated with fewer comorbidities (72.2%) compared to low (65.9%) and middle-income (68.4%) patients (p&lt;0.001). High-income patients were more likely to be treated at academic facilities (41.9%) compared to low (39.2%) or middle-income (35.4%) individuals (p&lt;0.001), which have longer survivability (58.9 months vs. 47.8 months in non-academic facilities; p&lt;0.001). Additionally, high income was also associated with increased rates of private insurance ownership (38.0%) while low-income individuals were more likely to have Medicaid (9.5%) or be uninsured (5.1%; p&lt;0.001). No significant differences were found in tumor grade or differentiation, staging, metastasis, or surgical margins. Conclusions: This study indicates an association between high-income patients and increased survivability, while also observing an association with low-income and decreased survivability. Further research is required to assess specific environmental risk factors of adenomatous neoplasms and their relation to income level.
Fruquintinib combined with sintilimab plus transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma: A single-arm phase II study.
Authors: Guoliang Shao, Hui Zeng, Zhewei Zhang, Jun Luo, Dinghu Zhang
Journal: Journal of Clinical Oncology (2024)

499 Background: Tyrosine kinase inhibitor combined with immune checkpoint inhibitor has been reported a synergetic survival benefit in patients with unresectable hepatocellular carcinoma (uHCC). TACE induces tumor necrosis and tumor antigen release was believed to increase immune responses of anticancer immunotherapies. This study aimed to evaluate the safety and efficacy of fruquintinib combined with sintilimab plus TACE for uHCC. Methods: This study was a single-arm, open-label phase Ⅱ exploratory clinical study (NCT05971199). Eligible patients were China liver cancer stage (CNLC) Ⅱb-Ⅲa and not candidates for surgical resection or ablation, or liver transplantation, at least one target lesion evaluable, ECOG performance status of 0-1, and Child-Pugh score ≤7. Enrolled patients would receive treatment with TACE (TACE was repeated on demand, but &lt; 5 times) followed by sintilimab 200 mg every 3 weeks and fruquintinib (5 mg QD, 2w on/1w off) until intolerable toxicity or disease progression. The primary endpoint was progression free survival (PFS). The secondary endpoints included adverse events (AEs), overall survival (OS), objective response rate (ORR) and disease control rate (DCR) per mRECIST. Results: As of August 20, 2023, 15 enrolled patients with uHCC were treated. Mean follow-up time is 10.7 months. The median age was 58 years. At present, 10 patients were included for efficacy and safety analysis evaluation. Number of patients with CNLC stage Ⅱb and Ⅲa was 0 (0 %) and 15 (100 %), respectively. The median PFS and OS data are not yet mature. The ORR and DCR were 80% and 100% respectively based on mRECIST (1 CR, 10%; 7 PR, 70%; 2 SD, 20%). The most common (≥ 10%) TRAEs (≥ Grade 3) were elevated glutamic oxaloacetic transaminase, hypertension, proteinuria. No unexpected toxicity or treatment-related deaths occurred. Conclusions: Fruquintinib combined with sintilimab and TACE is a promising and tolerable therapeutic regimen for patients with CNLC Ⅱb-Ⅲa uHCC. This study is still ongoing and further follow-up is required to obtain final survival results. Clinical trial information: NCT05971199 .
Molecular predictors of response to first-line systemic therapies in advanced hepatocellular carcinoma.
Authors: Jeremy Chang, Elizabeth Conner, Kathryn J Fowler, Pablo Tamayo, Adam Burgoyne
Journal: Journal of Clinical Oncology (2024)

534 Background: With numerous advances in systemic therapy for advanced hepatocellular carcinoma (HCC) over the past several years, there are now multiple first-line treatment options which can be considered. These options include combination atezolizumab with bevacizumab (atezo/bev), programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) targeted agents, and oral multikinase inhibitor monotherapy. However, further guidance is needed to predict which patients will respond to best to each regimen. Methods: We performed a single center, retrospective study to determine the association between responses to first-line therapies in advanced HCC and various molecular alterations. Patients received first-line therapy with either atezo/bev, PD-1/PD-L1 monotherapy, or oral multikinase inhibitor monotherapy with treatment responses determined by imaging. All patients underwent next-generation sequencing (NGS) with testing performed on peripheral blood or tumor tissue. Results: A total of 116 patients with advanced HCC were included in this study. For first-line therapies, 45 (38.8%) patients received atezo/bev, 41 (35.3%) received oral multikinase inhibitor monotherapy, and 30 (25.9%) received PD-1/PD-L1 monotherapy. There was no association between treatment responses and patient ethnicity, age, or underlying cirrhosis etiology for any regimen. However, when analyzing NGS results, atezo/bev recipients with telomerase reverse transcriptase (TERT) promoter alterations had significantly higher rates of disease progression (PD) compared those without TERT promoter alterations (91.7% vs 54.6%, p = 0.03). In addition, in the oral multikinase inhibitor monotherapy group, those with CTNNB1 alterations had significantly greater PD rates compared to patients without these alterations (66.7% vs 31%, p = 0.04). There were no significant correlations between molecular alterations and responses in the PD-1/PD-L1 monotherapy group (Table). Conclusions: In our study, advanced HCC patients who received first-line systemic therapies were found to have significant correlations between TERT promoter and CTNNB1 alterations and responses to atezo/bev and oral multikinase inhibitor monotherapy, respectively. Given the widespread use of these regimens in the HCC treatment paradigm, additional studies are needed to confirm these findings and determine their impact on survival outcomes.[Table: see text]
Survival after esophagectomy for metastatic esophageal cancer: Should surgery’s role be reconsidered?
Authors: Samir H Saeed, Andrew J Sinnamon, Jacques P Fontaine, Rutika Mehta, Jobelle Joyce Anne Baldonado, Luis R Pena, Russell F Palm, Sarah E. Hoffe, Jessica M. Frakes, Jose Mario Pimiento
Journal: Journal of Clinical Oncology (2024)

410 Background: Standard treatment for stage IV esophageal cancer (EC) is systemic therapy, with surgery considered contraindicated. The objective of this study is to assess the impact of surgical resection on outcomes for patients with metastatic EC. Methods: We reviewed our institution’s IRB-approved database of 1334 esophagectomies from 1994 to 2023 and identified 18 patients with distant disease (stage IV) by AJCC8 found prior to or during surgery. Chi-Square, ANOVA, and Kaplan-Meier survival analyses were used to compare demographics, clinical characteristics, and survival from time of surgery in those with metastatic versus non-metastatic EC. Results: Most metastatic patients were male (89%), Caucasian (83%), and had adenocarcinoma (89%). Compared to the non-metastatic cohort, stage IV EC cases were younger (57 vs 63; p=0.03), non-Caucasian (17% vs 6%; p=&lt;0.001), and more likely to get chemotherapy (41% vs 8%; p=0.04) or immunotherapy (23.5% vs 0%; p=0.06), with no difference in gender (89% vs 83%) and receipt of chemoradiotherapy (94% vs 92%). While the difference in intra-operative complication rates was significant (13% vs 2%; p=0.001), both groups had similar rates of post-operative complications ( p=0.95). Non-regional nodal metastasis had the most favorable outcome (mOS NR; median follow-up=14m); while peritoneal/omental disease had the shortest survival (5.2m). Patients receiving surgery more than a year after stage IV diagnosis ( n=6) had better survival than those who either underwent resection within a year after diagnosis ( n=2) or had metastasis identified at time of surgery ( n=8) ( p=0.02). PDL-1 positive and HER2-neu positive tumors also had better outcomes, with neither group reaching median survival. Conclusions: Esophagectomy for highly selected patients with distant disease demonstrates similar post-operative complication rates to locally advanced EC. For stage IV patients, a short interval from diagnosis to surgery is associated with worse survival; however, prolonged diagnosis-to-surgery interval &gt;12m and PDL-1 and HER2-neu positivity demonstrate better outcomes. Surgery’s role in treatment of stage IV EC preferably more than a year after diagnosis of metastasis should be further studied.
Real-world testing, treatment patterns, and outcomes following liquid biopsy in advanced cholangiocarcinoma.
Authors: Amit Mahipal, Keelia M. Clemens, Jiemin Liao, Caroline M. Weipert, Leslie Bucheit, Moh'd M. Khushman
Journal: Journal of Clinical Oncology (2024)

455 Background: Cholangiocarcinoma (CCA) is an aggressive cancer with a poor prognosis. Given failure rates of up to 27% of CCA tissue biopsies, liquid biopsy has become an important tool to identify actionable molecular alterations. It is estimated tissue-based testing identifies IDH1 mutations and FGFR2 fusions in 12% and 9% of patients with advanced CCA (aCCA), respectively. Here we examined the rate of molecular alteration detection using circulating tumor DNA (ctDNA) testing, treatment patterns in aCCA, and outcomes for patients receiving ivosidenib following ctDNA-detected IDH1 mutations. Methods: Real-world data was sourced from GuardantINFORM, which comprises aggregated commercial payer health claims and de-identified records from &gt;330,000 patients with clinical ctDNA testing via Guardant360 (G360), from 2014 to 2023. Patients with aCCA and &gt;1 treatment claim after G360 results were included (N=1726). Patient outcomes were assessed via real-world time to treatment discontinuation (rwTTD), real-world time to next treatment (rwTTNT), and real-world overall survival (rwOS), all assessed in months. Log rank test was used to compare Kaplan-Meier survival curves. Results: Of 1495 patients with &gt;1 ctDNA alteration detected, a guideline-recommended biomarker was identified in 18% of patients. In patients with intrahepatic CCA (n=403), 11% had an IDH1 mutation, 9% an FGFR2 fusion, 1% MSI-H detected, 1% BRAF V600E mutation, &lt;1% ERBB2 amplification and &lt;1% RET fusion. Testing was performed prior to first-line therapy, after first-line therapy and after second-line therapy in 34%, 46% and 21% of patients respectively. Gemcitabine and cisplatin represented the most common first-line therapy (48%). FOLFOX (21%), gemcitabine and cisplatin (13%), and capecitabine (11%) were the most common second-line therapies. Among ivosidenib-naïve patients with an IDH1 mutation, 58 (20%) started therapy within 90 days of ctDNA test: 36% received ivosidenib, 57% received chemotherapy, 7% received other therapy. Patients with IDH1 mutations treated with ivosidenib (n=21) had numerically improved rwTTD and rwTTNT compared to those receiving chemotherapy (n=33) [rwTTD: 4.6 (95% CI:2.6-8.6) vs 2.8 (95% CI:2.0-6.3), p=0.1011; rwTTNT 11.0 (95% CI:5.7-NE) vs 5.2 (95% CI:3.3-NE); p=0.2559]. There was no difference in rwOS between patients receiving ivosidenib vs not. However, sample size was small. Conclusions: The rate of actionable molecular alterations detected via ctDNA is 18%, comparable to reports from tissue-based testing. Patients with aCCA are often tested before starting first or second LOT. Patients with ctDNA-detected IDH1 mutations treated with ivosidenib and had a trend toward improved rwTTD and rwTTNT, although it did not reach statistical significance. This data supports the clinical utility of liquid biopsy to identify aCCA patients who may benefit from targeted therapy.