tbuckley/cabot-search huggingface dataset:
Trends and disparities in palliative care utilization among patients with anal cancer: A ten-year retrospective study.
Authors: Ayobami Gbenga Olafimihan, Olanipekun Lanny Ntukidem, Inimfon Nsikak Jackson, Michael Russell Mullane
Journal: Journal of Clinical Oncology (2025)

2 Background: Anal cancer patients often experience high symptom burden and psychosocial distress. Early integration of palliative care (PC) in their management can improve health-related quality of life. We examined the trends and predictors of PC utilization among hospitalized anal cancer patients in the US. Methods: A retrospective longitudinal study using the NIS database (2010-2019) was conducted. Using joinpoint regression and multivariable logistic regression, trends and factors associated with PC receipt were assessed. Results: The overall prevalence of PC utilization in the cohort of about 70,000 admissions with anal cancer was 6.9%. PC consultations increased from 3,372 to 11,081 per 100,000 anal cancer hospitalization (p-trend &lt;0.001) with an average annual percentage change of 12.8%. Individuals ≥ 60 years with anal cancer had lower odds (Adjusted odds ratio (AOR): 0.81; 95% CI: 0.68-0.97) of receiving PC compared to their counterparts &lt; 60 years. Patients in the second (AOR: 1.31; 95% CI: 1.05-1.62), and fourth (AOR: 1.29; 95% CI: 1.01–1.64) median household national income quartiles had about 30% greater likelihood of utilizing PC relative to those in the first income quartile. Patients in teaching hospitals had 40% higher likelihood (AOR: 1.40; 95% CI: 1.14-1.71) of PC in comparison to patients in non-teaching hospitals. Relative to patients who had a routine discharge home or with self-care, those discharged to facilities or with home health care were five-fold more likely (AOR: 5.04; 95% CI: 4.09-6.20) to receive PC. Those who died during hospitalization were also more likely to utilize PC (AOR: 33.9; 95% CI: 24.9-46.1). Other factors associated with PC receipt were non-elective admissions and higher Comorbidity burden. Conclusions: Though the trends in PC utilization have improved over the years, it remains suboptimal. Older patients were less likely to receive PC. Targeted interventions are needed to narrow the identified disparities for optimal utilization of PC in this patient population. Factors predicting the use of palliative care among hospitalized anal cancer patients. a Unadjusted Odds Ratio (95% CI) Adjusted Odds Ratio (95% CI) Age “60 years and above “vs “Less than 60” 0.98 (0.86-1.12) 0.81 (0.68-0.97) Hospital region South vs Northeast 1.04 (0.84-1.29) 1.33 (1.04-1.69) West vs Northeast 1.28 (1.02-1.61) 1.39 (1.06-1.82) Hospital Teaching Status Teaching vs Nonteaching 1.36 (1.16-1.60) 1.40 (1.14-1.71) Patient disposition Transfer to facility/home health care vs Routine discharge 4.98 (4.14-5.99) 5.04 (4.09-6.20) Died vs Routine discharge 39.4 (30.2-51.4) 33.9 (24.9-46.1) Admission type Non-elective vs Elective 2.97 (2.39-3.68) 2.91 (2.28-3.70) Median Household income national quartiles Quartile 2 vs Quartile 1 1.07 (0.90-1.29) 1.31 (1.05-1.62) Quartile 4 vs Quartile 1 1.17 (0.96-1.42) 1.29 (1.01-1.64) a CI = confidence intervals.
First-in-human phase 1/2 study (MYCHELANGELO I) of first-in-class epigenomic controller OTX-2002 targeting MYC oncogene in patients with hepatocellular carcinoma (HCC) and other solid tumors.
Authors: Jonathan Mizrahi, William Senapedis, Charles O'Donnell, J. Graeme Hodgson, Joseph V. Newman, Stephen Siecinski, Chia-Chi Lin
Journal: Journal of Clinical Oncology (2025)

606 Background: The c-MYC (MYC) oncogene is a master transcription factor of tumor cell and microenvironment regulation; it is often dysregulated in cancer, including HCC. OTX-2002 is a MYC-targeted Epigenomic Controller (MYC-EC), an mRNA drug substance encapsulated in a clinical lipid nanoparticle (LNP), designed to downregulate MYC expression pre-transcriptionally with high specificity and durability, inhibiting tumor cell viability while sparing normal cells. Methods: A first-in-human dose-escalation study (NCT05497453) investigates OTX-2002 monotherapy in HCC and other solid tumors. Key outcomes include safety, tolerability, pharmacokinetics (PK) and the recommended dose for expansion. In addition to standard safety measures, LNP-associated safety measures including cytokine profiling and an assessment of the presence of anti-PEG antibodies (ADA) were included. Initial pharmacodynamic activity (PD) was assessed via measurement of DNA methylation at the MYC locus in cell-free DNA [cfDNA] from whole blood. Results: As of August 23, 2024, 24 patients were treated at 6 doses (19 HCC, 1 colorectal, 1 cervical, 1 pancreatic, 2 sarcoma). OTX-2002 was generally well-tolerated; most adverse events (89%) were low grade, with infusion-related reactions being the most common (30%). Consistent with known LNP profiles, OTX-2002 adverse events were transient and manageable, including cytokine and ADA expression levels. Plasma PK exposures of OTX-2002 were linear across the first five doses analyzed. Significant, on-target dose-dependent changes in MYC gene methylation were seen in cfDNA for all patients post-dose and were durable for at least 15 days, consistent with the designed durability of the MYC-EC. Updated data will be presented. Conclusions: OTX-2002 is well-tolerated and induces rapid and durable epigenomic changes to the MYC locus. These results provide clinical proof of mechanism of the epigenomic controller platform and support continued development of OTX-2002. Clinical trial information: NCT05497453 .
Social determinants of health and financial burden among patients with pancreatic cancer at a tertiary cancer center.
Authors: Khalid Jazieh, Minji K Lee, Kimberly O. Steinert, Miranda Lin, Robert R. McWilliams
Journal: Journal of Clinical Oncology (2025)

678 Background: Financial toxicity (FT) represents a challenge for cancer patients that impacts treatment decisions, patient satisfaction, and quality of life. Social determinants of health (SDoH) screening may predict who is at risk of FT and could potentially benefit from financial interventions. Methods: This is a retrospective study of all cancer patients presenting to Mayo Clinic sites between Sept 2023 – Jun 2024. Patients completed SDoH questionnaires and were given risk scores of Low Risk, Medium Risk, and High Risk for SDoH categories: Financial Strain Risk, Transportation Risk, and Food Insecurity Risk. Patient financial data including active debt amounts, insurance coverage, and financial aid were collected. Patients with pancreatic ductal adenocarcinoma (PDAC) were compared to those with pancreatic neuroendocrine tumors (PNET) and patients with other cancers (Others). Categorical variables were compared with Pearson's Chi-squared test, continuous variables with Kruskal-Wallis rank sum test. P values &lt; 0.05 were considered significant. Results: Data was obtained from 88,039 patients, 2,607 of whom had PDAC and 449 had PNET. Compared to PDAC patients, PNET patients and Others were more likely to have Medium/High risk scores for Financial Strain Risk (6% vs 6.5% and 8.5%, respectively) and Food Insecurity (1.7% vs 3.8% and 3.2%) (Table). There was no statistically significant difference in median medical debt and need of financial assistance between the groups. Among PDAC patients, there were differences in distributions among race, primary language spoken, and patient electronic record access depending on Financial Risk categories. African American patients had the greatest proportion of Medium/High risk (12.9%) compared to Asian (4.4%) and White (5.8%) patients (P&lt;0.001). Among patients with English as their primary language, 64.9% had Low Risk scores compared to 27.7% with other primary languages (P&lt;0.001). Patients with electronic record access were more likely to report High Risk scores (6.9%) compared to those without access (1.6%). Conclusions: Per patient responses collected, PDAC patients presenting to our center have lower risk of financial strain and similar medical debt levels compared to the remainder of cancer patients. Among PDAC patients, higher financial strain was experienced by non-whites (7.9% vs 5.8%). Diagnosis PDAC (N=2607) PNET (N=449) Other (N=84983) p value Current Financial Risk (Grouped) &lt; 0.001 - Low Risk 1662 (63.8%) 304 (67.7%) 59298 (69.8%) - Medium/High Risk 157 (6.0%) 29 (6.5%) 7209 (8.5%) - Unknown/Missing 788 (30.2%) 116 (25.8%) 18476 (21.7%) Food Insecurity Risk &lt; 0.001 - Low Risk 1764 (67.7%) 308 (68.6%) 63235 (74.4%) - Medium Risk 45 (1.7%) 17 (3.8%) 2703 (3.2%) - Unknown/Missing 798 (30.6%) 124 (27.6%) 19045 (22.4%) Median Active Debt in USD 1102.230 1020.010 1141.135 0.593
Tislelizumab (TIS) + chemotherapy (chemo) vs placebo (PBO) + chemo as first-line (1L) treatment in gastric/gastroesophageal junction adenocarcinoma (GC/GEJC) patients with/without peritoneal or liver metastases: A post hoc analysis of RATIONALE-305 study.
Authors: Miaozhen Qiu, Huiyan Luo, Feng-Hua Wang, Feng Wang, Ming-Ming He, Sheng Xu, Xiaoxi Pan, Rui-Hua Xu
Journal: Journal of Clinical Oncology (2025)

414 Background: Gastric cancer patients with peritoneal or liver metastases had poor prognosis, and the efficacy of immunotherapy in these patients remains unclear. The global phase 3 RATIONALE-305 study (NCT03777657) demonstrated that tislelizumab combined with chemotherapy could bring survival benefits to 1L treatment of GC/GEJC patients. Here, we assessed the efficacy of TIS + chemo vs PBO + chemo in patients with/without peritoneal or liver metastases in RATIONALE-305. Methods: Patients with systemic treatment-naïve GC/GEJC were randomly assigned (1:1) to receive either TIS + chemo or PBO + chemo. Regression analyses were conducted to explore the associations between peritoneal or liver metastases and OS. Relative treatment effect between tislelizumab and placebo was assessed in each subgroup. The Kaplan-Meier method was used to estimate the median OS, and hazard ratios (HRs) for OS were estimated using Cox proportional hazards models. Results: Among the 997 randomized patients (TIS + chemo, n=501; PBO + chemo, n=496), 434 (43.5%) had peritoneal metastases (220 in TIS arm; 214 in PBO arm) and 378 (37.9%) had liver metastases (190 in TIS arm; 188 in PBO arm) at baseline. Regression analyses showed peritoneal and liver metastases were significantly associated with shorter OS. Baseline characteristics were balanced between TIS and chemo arms within each subgroup, including PD-L1 expression levels. As of data cut-off on Feb 28, 2024, OS was longer in the TIS arm compared with the PBO arm in patients with peritoneal metastases (HR= 0.78, 95% CI 0.64-0.96) or without (HR = 0.79, 95% CI 0.65-0.95). OS improvement was also observed in patients with liver metastases (HR = 0.77, 95% CI 0.62-0.96) or without (HR = 0.80, 95% CI 0.67-0.95). Conclusions: This post hoc analysis demonstrated OS improvement with TIS + chemo vs PBO + chemo in GC/GEJC patients with/without peritoneal or liver metastases. To our knowledge, RATIONALE-305 is the first global pivotal study reporting survival benefits with TIS + chemo as 1L treatment for GC/GEJC, irrespective of peritoneal or liver metastases. Clinical trial information: NCT03777657 . With metastases Without metastases TIS arm PBO arm TIS arm PBO arm Peritoneum n=220 n=214 n=281 n=282 Median OS, mo (95% CI) 12.3 (10.6-14.3) 11.8 (10.6-13.0) 17.3 (15.0-20.3) 14.0 (12.6-16.0) HR (95% CI) 0.78 (0.64-0.96) 0.79 (0.65-0.95) Liver n=190 n=188 n=311 n=308 Median OS, mo (95% CI) 13.9 (11.4-15.6) 12.9 (10.9-14.5) 16.0 (13.6-18.0) 12.9 (11.9-14.4) HR (95% CI) 0.77 (0.62-0.96) 0.80 (0.67-0.95)
Updated results from the phase Ib/II study of fruquintinib combined with SOX and toripalimab in patients with advanced metastatic gastric/gastroesophageal junction adenocarcinoma (GC/GEJC).
Authors: Xiangrui Meng, Zhengzheng Shan, Lulu Guan, Xin Dao, Qingxia Fan, Feng Wang
Journal: Journal of Clinical Oncology (2025)

423 Background: The efficacy of first-line treatment in advanced GC/GEJC patients (pts) with negative or low PD-L1 expression still needs to be improved. This phase Ib/II, open-label study (NCT05024812) evaluating fruquintinib (a highly selective VEGFR-1, -2, -3 inhibitor) plus toripalimab (anti-PD-1), and SOX has shown preliminary antitumor activity as first-line therapy in GC/GEJC. Here we update the results with longer follow-up duration and a specific focus on PD-L1 CPS features. Methods: The study of phase Ib employed a 3+3 dose escalation design, pts were treated with fruquintinib 3mg/d (dose level; DL1), 4mg/d (DL2), or 5mg/d (DL3) po, d1-14, in combination with fixed dose of toripalimab (240mg, iv, d1), oxaliplatin (130 mg/m 2 , iv, d1) and S-1 (40-60mg based on BSA, po, d1-14) every 3 weeks. It had been reported in phase Ib that fruquintinib 5mg/d was defined as the RP2D. In phase II, a further 64 pts would be treated with the same regimen. Primary endpoint of phase II was PFS per RECIST 1.1. Secondary endpoints included ORR, DCR, OS, DOR and safety. Results: As of August 15, 2024, 32 pts (9 in phase Ib; 23 in phase II) had been enrolled. Pts characteristics included: median age 62 (range 38–73); 66% male; 88% with ECOG PS 1, and 31% with liver metastasis. 31 pts had PD-L1 CPS available. 40.6% were CPS &lt; 1 and 68.8% were CPS &lt; 5. Of the 30 pts evaluable for tumor response, the ORR was 63.5% (95% CI 43.9–80.1) with 4 pts achieving complete responses and DCR was 96.7% (95% CI 82.8–99.9). After a median follow-up of 10.94 months, the median PFS was 9.33 (95% CI: 5.68–NA) months and OS result was not reached. Pts with CPS &lt; 5 were more likely to achieve higher response rate (65.0 vs 55.6%) and longer PFS than CPS ≥5 (12.68 vs 8.11 months). Similar trends were observed in pts with CPS &lt; 1 and CPS ≥1 (ORR: 75.0 vs 52.9%; PFS: 12.68 vs 8.11 months). Treatment-related adverse events (TRAEs) were mainly grade 1-2 and the most common ones were hypoalbuminemia (50%), neutrophil count decreased (34%), anemia (41%), platelet count decreased (34%) and white blood cell decreased (34%). Grade 4 TRAEs occurred in 2 pts (impaired liver function, hypertriglyceridemia). There were no treatment related deaths in the trial. Conclusions: Fruquintinib combined with SOX and toripalimab provided favorable efficacy and manageable toxicity profile as first-line therapy for pts with advanced metastatic GC/GEJC, especially in pts with negative or low PD-L1 expression. More data including the potential predictive response biomarkers would be further analyzed and reported. Clinical trial information: NCT05024812 .
Effect of marital status and race on survival of patients with well differentiated neuroendocrine tumors (NETs).
Authors: Amy D. Stringer, Lekhya Kollu, Brian L. Egleston, Namrata Vijayvergia
Journal: Journal of Clinical Oncology (2025)

654 Background: Socioeconomic status factors (SES) such as marital status, income, and race can influence and enhance disparities in cancer incidence and outcomes. Marriage has documented positive impacts on overall survival of numerous cancer types. Consequences of divorce have been less explored. The unique indolent, secretory nature of NETs may be differentially affected by SES factors. This study identifies implications of marital status and sex on 5-year survival rates of different racial groups diagnosed with NETs within the Surveillance, Epidemiology, and End Results (SEER) database between 2000-2020 while controlling broadly for the type of treatment received. Methods: Within the SEER data base patients with reported sex, race, marital status and treatment who were diagnosed with well differentiated NETs were selected excluding carcinomas. Relative and disease specific 5-year survival analyses were calculated with 95% confidence intervals and age standardized. Three groupings were analyzed single, separated/divorced/widowed and domestic-partner/married. Results: For all races and sexes, relative survival for individuals in a union was higher than those who were single, or separated, divorced/widowed [86.9% (CI 86.1% - 87.7%); 79.3% (77% to 81.3%); and 79.2% (78% to 80.3%) respectively]. When individuals of each marital status group were compared by matching sex and race, there were no significant differences in relative survival. But males of any race who left a union had lower chances of survival than corresponding females [72.4% (69.7% to 74.9%) vs 81.6% (80.3% to 82.8%)]. As expected, all groupings who received surgical treatment had a higher relative survival than those who did not. Those who received surgical treatment while in a partnership had a higher relative survival then those who were separated [94.5% (93.6% to 95.3%) vs 88.7% (87.3% to 89.9%)]. All marital groupings who underwent surgery or did not, had comparable relative survival between races; except, black individuals in a partnership had improved outcomes compared to the white population. More specifically, when accounting for race, sex, marital status and treatment received, black men who did not undergo surgery had a higher relative survival compared to white men [69.9% (62.2% to 76.3%) vs 59.4% (56.6% to 62.1%)]. All the same conclusions were statistically significant for disease specific survival. Conclusions: Due to NETs slow growing nature SES factors play a major role in the care of patients living with them. Our findings demonstrate generally, irrespective of race, sex, or surgical treatment, being involved in a union is advantageous, showing a protective effect on patient survival, while parting from a union could be deleterious as it is tied to less favorable outcomes. These findings underscore the importance of considering these factors in treatment and care strategies.
Interim safety and efficacy data of [ <sup>212</sup> Pb]VMT-α-NET in somatostatin receptor 2 (SSTR2) expressing neuroendocrine tumors (NETs).
Authors: Richard L. Wahl, Lowell Brian Anthony, Lilja B. Solnes, Samuel H. Mehr, Lucia Baratto, Alaa Hanna, Wenjing M. Yang, Stephen Michael Keefe, Thorvardur Ragnar Halfdanarson
Journal: Journal of Clinical Oncology (2025)

668 Background: After the approval of 177Lu DOTATATE, a new generation of radiopharmaceutical therapies (RPT) utilizing alpha-emitting radiometals is being developed as front-line therapies for advanced NETs with the hope of higher clinical efficacy. In this Phase I study, [ 212 Pb]VMT-α-NET, a novel targeted alpha radionuclide therapy (TAT) to SSTR2, is being evaluated in SSTR2-expressing NETs tumors in patients with no prior PRRT treatment. Here we present interim safety and the first efficacy results from dose escalation cohorts 1 and 2. Methods: In this first-in-human dose-escalation study, safety, PK, and efficacy of [ 212 Pb]VMT-α-NET were investigated in a population of well-differentiated adult NETs of any grade which progressed after prior standard of care therapy as assessed by RECIST v1.1 (NCT05636618). No patient may have received prior 177 Lu-DOTATATE or PRRT. The dose escalation design includes four cohorts, 3 mCi, 5 mCi, 7.5 mCi and 10 mCi based on a Bayesian modified toxicity probability interval (mTPI-2) design. Subjects in cohorts 1 and 2 underwent dosimetry evaluations using the therapeutic surrogate [ 203 Pb]VMT-a-NET. Therapeutic [ 212 Pb]VMT-a-NET was administered for 4 cycles Q8W in combination with reno-protective amino acids. The DLT assessment period is defined as the first 6 weeks of cycle 1. The primary objectives include the evaluation of safety and tolerability, the PK and RP2D of [ 212 Pb]VMT-a-NET as well as ORR as assessed by RECIST 1.1 criteria. Results: The current data cut occurred on September 19 th , 2024. A total of 9 patients were enrolled (2 in cohort 1 and 7 in cohort 2). Median exposure for cohort 1 was 2.5 mCi (2.5 mCi, 2.5 mCi) and for cohort 2 was 5.1 mCi (4.7 mCi, 5.2 mCi). No DLTs were observed. Two grade 3 AEs occurred in Cohort 2 (diarrhea, syncope). The most frequent related TEAE were alopecia, fatigue, anemia, lymphopenia and nausea (all grade 1 or 2). One subject in Cohort 2 was discontinued due to progressive disease. Landmark PFS at 9 months is 89%. ORR is not yet mature and will be shown at the time of the meeting. Safety Monitoring Committee (SMC) meeting was held on July 17 th , 2024, recommended dose escalation to cohort 3 at 7.5 mCi. No nephrotoxicity was reported in either cohort. Conclusions: [ 212 Pb]VMT-α-NET is safe up to 185 MBq (5 mCi) dose level, and the SMC supported dose escalate to cohort 3 at 277.5 MBq (7.5 mCi) following a mandated FDA review in fall. Cohort 2 remains open for dose level expansion. Early efficacy results demonstrate encouraging progression-free survival. Clinical trial information: NCT05636618 .
Patient-centered adverse event reporting in clinical trials: A novel approach using ECOG-ACRIN E2211.
Authors: Wan Ying Tan, Laura D. Cramer, Noah Graham, Namrata Vijayvergia, Maryam B. Lustberg, Al B. Benson, Pamela L. Kunz
Journal: Journal of Clinical Oncology (2025)

658 Background: The Common Terminology Criteria for Adverse Events (CTCAE) classifies adverse events (AEs) in clinical trials but traditionally limits the analysis to a single occurrence per patient and grade 3-4 AEs, overlooking frequent and lower grade AEs. We propose a new approach of AE reporting that captures both the safety profile and patient experience. Methods: We analyzed related AEs collected in the ECOG-ACRIN E2211 [Phase II capecitabine + temozolomide (Arm A) vs. temozolomide (Arm B) in advanced pancreatic neuroendocrine neoplasms] by CTCAE v4.0 and limited to hematologic and gastrointestinal (GI) categories for this exploratory analysis. We calculated AE burden, defined as the average occurrence of AE per patient experiencing the AE, measured by total occurrence of AEs, and divided by number of patients who developed the AE. We then compared burden of grade 3-4 AEs vs. grades 1-4 AEs. Sex differences were evaluated using t-tests. Results: For hematologic AEs, 72 patients reported 426 occurrences across grades 1-4 and 24 patients reported 39 occurrences for grades 3-4, resulting in AE burdens of 5.9 (grades 1-4) versus 1.6 (grades 3-4). For GI AEs, 108 patients reported 997 grade 1-4 events, and 13 patients reported 22 grade 3-4 events, resulting in AE burdens of 9.23 versus 1.69, respectively. Sex differences in AE burden are tabulated below (Table). For example, in Arm B, anemia burden was 4.8 (males) vs 2.7 (females) [p=0.068] for grades 1-4 and 0 (males) vs 1 (females) for grades 3 and 4. Conclusions: This AE reporting approach, accounting for the burden across grade 1-4, offers a different and more patient-centered assessment of AEs in clinical trials and may help better identify sex-based differences. Burden of AEs by treatment arm and sex distribution. Burden of Related AEs Categories of AEs Arm A (N=65) Arm B (N=68) Grade 1-Grade 4 Grade 3-Grade 4 Grade 1-Grade 4 Grade 3-Grade 4 Male Female p-value Male Female p-value Male Female p-value Male Female p-value Hematologic Anemia 2.9 3 0.937 0 0 4.8 2.7 0.068 0 1* Neutropenia 1.7 2.2 0.686 1 1* 1.2 2.3 0.064 1 1.1 0.356 Thrombocytopenia 4.3 2.6 0.241 1* 1.2 3.6 3.3 0.781 1 1 ** Gastrointestinal Abdominal pain 2.5 2.2 0.835 0 0 3.1 3 0.955 0 1* Constipation 4.1 3.2 0.515 1* 0 4.9 3.3 0.169 0 0 Diarrhea 1.8 3.6 0.158 0 0 2.6 2.5 0.940 1.25 1 0.390 Nausea 4.2 4.9 0.619 0 0 4.4 4.2 0.893 1 1** ** Vomiting 2.2 1.9 0.703 0 0 1.8 2.8 0.241 1 1 ** *Only 1 patient in each group **No variance within each group.