tbuckley/cabot-search huggingface dataset:
A qualitative exploration of perceptions and experiences towards physical activity among patients with pancreatic ductal adenocarcinoma undergoing treatment.
Authors: Tyra Nguyen, Gillian Gresham, Bianca Luna-Lupercio, Carolina Raines, Jun Gong, Arsen Osipov, Andrew Eugene Hendifar, Celina Shirazipour
Journal: Journal of Clinical Oncology (2024)

646 Background: Patients with pancreatic ductal adenocarcinoma (PDAC) experience significant symptom burden due to the disease and its treatment, thus limiting their ability to participate in physical activity (PA) and engage in daily activities. PA can have many physical and psychosocial benefits, and exploring its value and how to deliver it to patients with PDAC could support their health and well-being. Therefore, the objective of this qualitative research was to explore perceptions and experiences of PA among PDAC patients undergoing active treatment. Methods: Qualitative semi-structured interviews were conducted with individuals with PDAC. Participation was optional and open to individuals in the DigiSTEPS prospective trial evaluating associations between PA measures, performance status, and patient-reported outcomes (NCT03757182). Interviews were conducted virtually. Data were analyzed using inductive thematic analysis. Results: Ten patients (50% male, 80% white, mean age=70 years) participated in the interviews. While clinical approaches may often be informational and seek to educate PDAC patients regarding the importance of PA and the benefits of PA participation, findings suggest that participants understand the benefits of PA and are interested in being active. However, cancer symptoms and treatment-related side effects are substantial barriers that are hard to surmount. A further barrier was the dissonance in self-perceptions, particularly the contrast in their functional abilities and body composition pre- to post-cancer diagnosis. We identified four action items to support patients in overcoming these barriers: clinicians can leverage trust in their team to provide evidence-based information on how to be active; distribute wearable activity monitors which can increase motivation; harness virtual PA opportunities during more symptomatic periods; and provide PA trainers with cancer knowledge to tailor programming. Conclusions: This research highlights the importance of tailoring PA discussion and approaches based on a PDAC patient’s phase in the cancer survivorship continuum, their stage at diagnosis, and treatment type. In addition, clinical teams and trainers should consider patient concerns related to body image and develop programs that address the barriers identified in this research. Clinical teams may benefit from integrating access to counselling psychologists to address these concerns and promote PA in positive and adaptive ways. Clinical trial information: NCT03757182 .
Angiotensin receptor blockers and severe diarrhea and/or enterocolitis induced by CAPOX in patients with colorectal cancer: A multicentric cohort.
Authors: Adriano Fernandes Fernandes Teixeira, Tiago Cordeiro Felismino, Mauro Daniel Spina Donadio, Greta Catani, Ana Luiza Mattos Da Silva, Rui Fernando Weschenfelder, Juan Manuel O'Connor, Anelisa Kruschewsky Coutinho, Rachel Riechelmann
Journal: Journal of Clinical Oncology (2024)

88 Background: While patients (pts) with colorectal cancer (CRC) treated with CAPOX (capecitabine and oxaliplatin) may experience severe diarrhea, risk factors for this toxicity remain undetermined. We have previously shown that concurrent use of angiotensin receptors blockers (ARB), a known inhibitor of TGF-B which is important for gut mucosa proliferation, significantly increased the risk of severe diarrhea and/or enterocolitis. Here we conducted a larger and multicenter study to validate this finding, adjusting for other risk factors. Methods: Multicenter retrospective cohort of CRC pts who received ≥ 1 cycle of CAPOX. The primary endpoint was grade (G) ≥ 3 diarrhea and/or enterocolitis as described by Common Terminology Criteria for Adverse Events version 5.0. Clinical data were retrieved from medical charts. Unadjusted logistic regression was used to evaluate risk factors for ≥ G3 diarrhea/enterocolitis (use of ARBs or angiotensin-converting enzyme inhibitors [ACEi], age, ECOG, Age-adjusted Charlson Comorbidity Index [A-CCI], sidedness, presence of ileostomy, treatment intent [curative vs palliative], use of proton pump inhibitors or antiacid, and center). A multivariable analysis was performed with variables with P &lt; 0.05 deemed significant. Results: From April/2010 to December/2023, 348 pts were included: 175 (50.3%) were female, median age was 61 years (28 - 87), 259 (74.4%) had stage III and 76 pts (21.9%), stage IV. 58 pts (16%) had G3 ≥ diarrhea/ enterocolitis, mostly before 3 rd cycle. Age ≥ 65 years (Odds ratio [OR] 3.18; P &lt; 0,0001; 95% CI, 1.78 to 5.68 ); right-sided tumors (OR 1.73; P=0.075; 95% CI, 0.95 to 3.17); use of ARBs or ACEi (OR 1.57; P=0.127; 95% CI, 0.88 to 2.79); A-CCI (OR 1.12; P=0.042; 95% CI, 1.004 to 1.23) were associated with ≥ G3 diarrhea/enterocolitis in univariate analyses. In the multivariable analysis, age ≥ 65 years was significant (OR 3.13; P=0.001; 95% CI, 1.58 to 6.20), but use of ARBs or ACEi was not significant (OR 1.16; P=0.635; 95% CI, 0.62 to 2.13). Five out of 9 pts who used Olmesartan had ≥ G3 diarrhea/enterocolitis. Conclusions: Among pts treated with CAPOX, ≥ 65 years, but not use of ARBs or ACEi, was an independent risk factor for ≥ G3 diarrhea/enterocolitis. Concurrent Olmesartan and CAPOX should be used with caution.
Single cell transcriptomic profiling of appendiceal adenocarcinoma to identify rare tumor cells and a myeloid-enriched tumor microenvironment (TME).
Authors: Betul Beyza Gunes, Nicholas James Hornstein, Mingshuang Wang, Saikat Chowdhury, Mahmoud M.G. Yousef, Abdelrahman M.G. Yousef, Mohammad A. A. Zeineddine, Michael White, John Paul Y.C. Shen
Journal: Journal of Clinical Oncology (2024)

760 Background: Appendiceal adenocarcinoma (AA) is a rare malignancy with distinct clinical and molecular characteristics compared to colorectal cancer (CRC). Currently there is little knowledge regarding how tumor cells from AA interact with the tumor microenvironment (TME). In this study, we performed single cell RNA sequencing (scRNAseq) on metastatic AA tumors taken from three patients undergoing curative intent surgical resection. Methods: After obtaining informed consent, tumor tissue from three patients with AA and one patient with CRC undergoing cytoreductive surgery at the MD Anderson Cancer Center (MDACC) was harvested and dissociated into single cell suspension for scRNAseq; libraries were prepared with ‘5 sequencing (10X Genomics). Bulk RNA sequencing from 19 additional patients with AA was available as a validation cohort. Results: scRNAseq analysis of a cohort of 3 patients with AA, 1 with CRC, and 12 healthy control samples identified 39,451 evaluable single cells after filtering and doublet removal. Separating cells into immune, stromal, and epithelial compartments identified that epithelial cells are rare in AA tumors. On average, AA constituted 62% stroma, 36% immune and only 2% epithelial cells, in contrast to healthy appendix (46% immune, 29% epithelial, 25% stroma). Sub-classification of immune cells revealed enrichment of myeloid cells in AA tumors (67% myeloid, 27% T, 5% B and 1% plasma B cells). This is in contrast to healthy appendix tissue (44% T, 26% plasma B, 22% B, 6% myeloid and 2% mast cells). In CRC, the majority of immune cells from the CRC sample were T cells (69%). These single cell data were used to improve deconvolution of bulk RNAseq, allowing for evaluation of TME contribution to transcription using bulk RNAseq data. Analysis of tumors from 19 patients with AA confirmed myeloid predominance in AA tumors. We performed pseudobulk differential expression analysis between compartments comparing CRC and AA which identified significant differences between compartments. Gene set enrichment analysis enabled identification of organized compartment specific changes. Conclusions: Findings from this study provide new insights into AA's biological distinctions from CRC and represent a crucial step toward better understanding this rare malignancy. Myeloid cells need further investigation in AA to develop specialized management approaches and improve patient outcomes.
An ARCAD database nomogram for prognostic prediction of treatment refractory metastatic colorectal cancer.
Authors: Eiji Oki, Hideaki Bando, Kentaro Yamazaki, Toshihiro Misumi, Yuriko Takeda, Motoko Suzuki, Masashi Wakabayashi, Masashi Wakabayashi, Axel Grothey, Robert J. Mayer, Jin Li, Thierry Andre, Qian Shi, Aimery De Gramont, Takayuki Yoshino
Journal: Journal of Clinical Oncology (2024)

107 Background: The "No Placebo Initiative" demonstrated that the survivals of patients (pts) receiving placebo in a salvage-line setting, exhibited no significant difference across trials (CORRECT, RECOURSE, CONCUR and TERRA). Therefore, we believe that a nomogram can be generated using the ARCAD database to predict survival of pts who completed standard therapy. Methods: Of 40,889 Individual patient data (IPD) from 59 studies, 723 pts received placebo from 4 randomized studies were pooled. The potential prognostic factors considered include BMI and Age. Imputed datasets were constructed by a multiple imputation method since the original dataset contains some missing values. Overall survival (OS) was defined as the time from randomization to death from any cause. Multivariate Cox proportional hazards models for OS were estimated based on the variables showing clinically and statistically significant by univariate analysis. Prediction performance of the final model was evaluated using the concordance index for survival data and calibration plots. Results: From univariate and multivariate analysis, ECOG performance status, Royal Marsden Hospital score (calculated by albumin level, LDH level, and number of metastatic site), primary site location, liver meta, peritoneal meta were selected as variables. We successfully developed a highly accurate nomogram to predict post-standard treatment prognosis for pts with mCRC. Concordance index for OS was 0.66. Conclusions: Although further validation in other cohorts is needed, this nomogram could be very useful to estimate the survival for clinical practice and enrolling in clinical trials. [Table: see text]
Real-world experience and outcomes of hepatocellular carcinoma (HCC) treated with transarterial radioembolization (TARE).
Authors: Parthib Das, Eric Min, Samuel Paul, Ashish Manne
Journal: Journal of Clinical Oncology (2024)

463 Background: TARE has been the preferred choice of locoregional therapy to advanced HCC in recent years. We attempted to identify factors contributing to the success of TARE in this retrospective review. Methods: HCC patients who received at least one TARE between 1/1/2015 and 8/30/22 at Ohio State University were included in this study. The patient's baseline characteristics at diagnosis (BLC) were extracted by chart review with post-procedural complications and survival outcomes. Descriptive statistics and log-rank test for survival outcomes were conducted using JMP Pro 16 (SAS Institute Inc., Cary, NC). Results: Our cohort had 144 patients with median age of diagnosis (dx) of 65 years, 81 % Caucasians, 81% males, 5% and 51% with hepatitis B and C, respectively; 24% and 21% ascites (As) and hepatic encephalopathy (HE) at dx, respectively; 72% (n=125) had just one procedure (24 had two planned procedures which were considered as 1), 12% (17) and 1% (2) had second and third procedures for recurrence, respectively. Immune checkpoint inhibitor (ICI) and other systemic therapy (tyrosine kinase inhibitor (TKI) or ramucirumab (Ram)) were given to 27% (5 before and 34 after TARE) and 24% (5 before and 30 after TARE), respectively. Other HCC-related BLC includes the number of lesions 1 vs 2-3 vs multiple = 45% vs 33% vs 22%; single lobe vs two lobes = 66 vs 33%; portal vein tumor thrombosis (PVTT) = in main portal vein vs. non-main veins (left or right or lower level) vs no PVTT = 14% vs 10% vs 76%. Median overall survival (OS) and time to recurrence after the first TARE (TTR) were 11 and 4 months (m), respectively. The only BLC that significantly influenced TTR was As (3 vs 4 m, p=0.008). Factors impacting OS were discussed in the table. Follow-up imaging (median = 3m) was available for response evaluation in 107/144 (indeterminate response (IR) reported in 25), and the response noted was reflective of OS (objective response vs. disease progression vs indeterminate, 22 vs 6 vs 8.5 m, p&lt;0.001). Conclusions: Careful patient selection based on BLC and the use of ICI (before or after) could improve the outcomes in HCC patients treated with TRAE. Larger prospective studies are needed to validate the study. [Table: see text]
Retrospective cohort study to evaluate the efficacy and safety of T-DXd in HER2-positive unresectable advanced or recurrent gastric or gastroesophageal junction cancer: EN-DEAVOR study.
Authors: Koki Nakanishi, Yasuhiro Kodera, Hisato Kawakami, Akitaka Makiyama, Hirotaka Konishi, Satoshi Morita, Yukiya Narita, Naotoshi Sugimoto, Keiko Minashi, Motohiro Imano, Rin Inamoto, Hiroki Kume, Keita Yamaguchi, Wataru Hashimoto, Kei Muro
Journal: Journal of Clinical Oncology (2024)

274 Background: Relatively limited clinical data exists for patients who receive T-DXd treatment in the 3L+ setting for HER2-positive unresectable advanced/recurrent gastric or gastroesophageal junction cancer. Insufficient data exists on real world patient populations that are likely to be excluded from clinical trials (e.g., elderly patients, those with significant co-morbidities). Therefore, this study was designed to evaluate the real-world clinical effectiveness and safety of T-DXd in patients with HER2-positive gastric cancer. Methods: This study (UMIN000049032) was a real-world, multicenter, non-interventional, retrospective cohort study conducted in Japan. Patients with HER2-positive unresectable advanced/recurrent gastric or gastroesophageal junction cancer treated with T-DXd were enrolled. The patients were first administered T-DXd between Sep 2020, when T-DXd became available for clinical use in Japan, and Sep 2021. We followed up on these patients' records until Sep 2022. The endpoints were overall survival (OS), real-world progression-free survival (rwPFS), time to treatment failure (TTF), objective response (ORR), adverse events (AEs) of Grade ≥3, and adverse events leading to dose reduction, interruption, or discontinuation. Results: A total of 318 patients were enrolled, and 312 patients were analyzed, excluding 6 patients due to double enrollment or miss-enrollment (median age 70 years, performance status 0 or 1/≥2 [87%/12%], 43% patients with ascites). Median OS, rwPFS, and TTF were 8.90 months, 4.57 months, and 3.94 months, respectively. Overall ORR was 32.7%; it was 43.8% in the 226 patients with a target lesion. Regarding safety, the incidence of Grade ≥ 3 AEs was 48.4%. A total of 190/312 (60.9%) patients treated with T-DXd experienced dose reduction, interruption, or discontinuation of T-DXd treatment due to AEs. The most common reasons for dose reduction or interruption were neutrophil count decreased, anorexia, and malaise, while the most common reasons for discontinuation were interstitial pneumonia, anorexia, malaise, and nausea. Conclusions: This study demonstrates the effectiveness and safety of T-DXd in the 3L+ setting in real-world patients with HER2-positive gastric or gastroesophageal cancer. No new safety signals were identified on the basis of this study.
Comprehensive genomic analysis of molecular residual disease based on circulating tumor DNA in patients with postoperative colorectal cancer.
Authors: Qingqi Hong, Jingtao Zhu, Hexin Lin, Yinan Chen, Haoyu Bai, Linghua Yan, Li Xiao, Jun You
Journal: Journal of Clinical Oncology (2024)

156 Background: Despite receiving curative resection, a considerable percentage of colorectal cancer (CRC) patients still experience disease recurrence. The early detection of molecular residual disease (MRD) has the potential to improve risk assessment. Methods: A total of 104 patients with stage Ⅰ-Ⅳ CRC were enrolled, of which 259 serial plasma samples were collected. Multi-gene targeted sequencing was conducted on tumor and plasma samples to identify somatic variants. Results: Among the 104 patients, 14 cases had positive landmark MRD and 32 cases had positive longitudinal MRD. Patients with positive landmark MRD had significantly higher recurrence risk compared to those with negative landmark MRD (Hazard Ratio [HR]: 7.325; 95% CI, 2.877-18.647; P &lt; 0.001). Similarly, positive longitudinal MRD was associated with increased recurrence risk (HR: 9.385; 95% CI: 3.085-28.556; P &lt; 0.001), with a higher HR value. Positive MRD detection preceded CT confirmed recurrence in 85.7% of patients, with a median lead time of 198.5 days. In multivariate analysis, positive-MRD was the most significant prognostic factor for DFS. The combination of KRAS variant and MRD status improved the efficiency of prognostic prediction, the area under the curve value for the combination of MRD and KRAS was higher than MRD and KRAS. By analyzing the characteristic of cfDNA fragments, we found that mutation sites tended to be enriched in shorter cell free DNA (cfDNA) fragments. Conclusions: Our study demonstrated an excellent prognostic prediction potential of circulating tumor DNA-based MRD detection among postoperative CRC patients, especially the combination of KRAS variant and MRD improved the efficiency of risk stratification through MRD. This study may facilitate the incorporation of MRD and KRAS into prognostic prediction. Our study revealed that mutation sites tended to be enriched in shorter DNA fragments, providing valuable insights for future ctDNA detection method.
Potential biomarkers for treatment response in advanced non-pancreatic neuroendocrine tumors.
Authors: Sahithi Sonti, Katy Wang, Kristopher Attwood, Hans Minderman, Orla Maguire, Courtney Ryan, Nitika Sharma, Bhavana Konda, Renuka V. Iyer, Anuradha Krishnamurthy
Journal: Journal of Clinical Oncology (2024)

599 Background: Well-differentiated NETs are highly vascular and hence, inhibition of angiogenesis is of interest. VEGF, a key molecule in promoting angiogenesis, has also been shown to promote an immunosuppressive tumor microenvironment. Nintedanib, an oral inhibitor of FGFR1–3, VEGFR1–3 and PDGFRA, has previously been evaluated in a phase II clinical trial in well-differentiated, non-pancreatic NETs, where 83% of the evaluable patients were progression-free at 16 weeks and median PFS was 11 months. In preclinical studies, nintedanib has been shown to increase PD-L1 expression in tumor cells, which then results in improved outcomes with immune checkpoint inhibition. There are multiple indicators of T-cell exhaustion, including PD-L1 and LAG-3. LAG-3+ T-cells have been found to correlate with poor response to treatment in neuroendocrine neoplasms. Given these findings, this study evaluates serum VEGF and LAG-3 expression to determine potential biomarkers of response in patients treated with nintedanib. Methods: 27 sets of paired samples collected at baseline and 8-weeks post treatment with nintedanib, from clinical trial NCT02399215 were used for this study. With IRB approval, we tested for serum VEGFa and serum LAG-3 using Luminex test kits: HCKP1-11K-01 (LAG-3) and HCYTA-60K-01 (VEGFa). We compared the baseline, 8-week, and percentage change in serum VEGF and serum LAG-3 levels with Rd Cd8+ pAkt+ T-cells (activated cytotoxic T-cells) as a marker of immune activation, Rd CD25+ pAkt+ T-cells (regulatory T-cells) as a marker of immune suppression, and PFS. Results: The median VEGF levels at baseline and 8-weeks were 10.50 pg/mL and 11.90 pg/mL respectively. The median LAG-3 level at baseline and 8-weeks were 59000 pg/mL and 62900 pg/mL respectively. Higher VEGFa levels in the post-treatment samples were associated with poorer progression free survival (HR= 1.009, 95% HR CI: [0.999, 1.019], with P= 0.0760). Higher levels of VEGF at baseline were also associated with lower numbers of Rd CD8+ pAkt + cells (Pearson coefficient = -0.42, p-value 0.04) at baseline. Increased baseline CD25+ pAkt+ levels were positively correlated with percent change in serum LAG-3 levels between baseline and post-treatment samples. (Pearson Co-efficient: 0.45; p=value: 0.02). Conclusions: Elevated serum VEGFa levels at 8-weeks post treatment correlated with lower PFS. Serum VEGFa level is a potential indicator of effector T-cell suppression, as evidenced by low number of activated cytotoxic T-cells in patients with higher VEGFa levels at baseline. Higher baseline regulatory T-cells were associated with a greater increase in serum LAG-3 levels, suggesting that serum LAG-3 may be an indicator of an immunosuppressive tumor microenvironment.
Concordance among three programmed death-ligand 1 (PD-L1) scoring methods and their association with clinical outcomes of tislelizumab (TIS) monotherapy in esophageal squamous cell carcinoma (ESCC).
Authors: Yongqian Shu, Jufeng Wang, Zhendong Chen, Sung-Bae Kim, Chen-Yuan Lin, Ken Kato, Eric Van Cutsem, Wenting Du, Jingwen Shi, Tianyu Xia, Ruiqi Huang, Qiao Li, Yun Zhang, Zhirong Shen, Lin Shen
Journal: Journal of Clinical Oncology (2024)

390 Background: Multiple scoring methods and cutoffs have been developed to evaluate tumor PD-L1 expression status in patients with ESCC, and PD-L1 expression level has been associated with the degree of response to anti-programmed cell death protein 1 (PD-1)/PD-L1 therapy. Here, we retrospectively investigated concordance between three PD-L1 scoring methods and their association with clinical outcomes in RATIONALE-302, a phase 3 study of the anti-PD-1 antibody TIS vs investigator-chosen chemotherapy (ICC) as second-line treatment for advanced unresectable/metastatic ESCC (NCT03430843). Methods: Patients enrolled in RATIONALE-302 with evaluable PD-L1 expression by the tumor area positivity (TAP) score (based on visual estimation of positive tumor cells [TCs] and tumor-associated immune cells [ICs]) using the VENTANA PD-L1 (SP263) assay were categorized at a 10% cutoff. Stained slides from those patients were rescored post hoc using both combined positive score (CPS; based on counting positive TCs and ICs) at cutoff 10 and TC (based on counting positive TCs only) score at a 1% cutoff, thresholds currently used in ESCC for anti-PD-(L)1 therapy. Concordance at these thresholds was investigated. Clinical efficacy (overall survival [OS]) for PD-L1 subgroups was assessed. Results: Of 512 pts enrolled, 364 had evaluable TAP scores (TIS, n=180; ICC, n=184), of whom 355 had evaluable post-hoc CPS and TC scores (TIS, n=175; ICC, n=180). TAP score and CPS showed high concordance in terms of overall percentage agreement (OPA; 90% [95% confidence interval (CI): 86, 93]) and Cohen’s Kappa (0.79 [95% CI: 0.72, 0.85]), while TAP and TC scores had lower concordance (OPA: 78% [95% CI: 73, 82]; Cohen’s Kappa: 0.56 [95% CI: 0.47, 0.64]). OS benefit with TIS vs ICC in PD-L1 subgroups defined by TAP, CPS, and TC score cutoffs were generally similar (Table). Conclusions: OS subgroup analysis showed comparable treatment effect by TAP score at 10% cutoff, CPS at cutoff 10, and TC score at 1% cutoff based on SP263 staining. TAP score and CPS at these cutoffs exhibited substantial concordance. The results indicate that the less time-consuming, visually estimated TAP score and CPS may be interchangeable for clinical measurement of PD-L1 expression in patients with ESCC. Clinical trial information: NCT03430843 . [Table: see text]