tbuckley/cabot-search huggingface dataset:
Real world prevalence of biomarkers for treatment of advanced gastric cancer or gastroesophageal junction cancer in a cohort of Colombian patients.
Authors: Diego Felipe Ballen, Kelman Ojeda, Ana Gualdron, Nicolas Tellez, Luisana Molina Pimienta
Journal: Journal of Clinical Oncology (2024)

402 Background: Gastric cancer (GC) is the leading cause of cancer-related deaths in Colombia, GLOBOCAN estimated 6.451 deaths in 2022. Development of immune checkpoint inhibitors and HER2 target therapy with chemotherapy had improved overall survival in advanced setting, but we do not have data about the prevalence of biomarkers used for selection of these patients in Colombia or Latin-America. Our aim is to describe the prevalence of biomarkers used currently for selection of treatment in a real-world multicenter cohort of advanced gastric and gastroesophageal junction (GEJ) cancer. Methods: We did a retrospective observational multicenter study of patients with advanced GC/GEJ cancer treated at three reference cancer centers in Bogota, Colombia between January 1, 2023 and July 31, 2023. We reviewed medical history and pathology reports looking for the prevalence of biomarkers used for selection of first line systemic therapy. Ventana 4B5 for HER2 IHQ evaluation and Dako 22C3 for PDL1 expression by CPS were used. MMR proteins were evaluated by IHQ nuclear expression. Results: 101 patients with advanced GC/GEJ were included. The median age was 61 years (range 18-83), 53,5% of patients were men, 92.1% were gastric cancer and 87,1% were de novo stage IV. Signet ring cells were found in 40%, peritoneal carcinomatosis was documented in 59% and 75,2% were distal tumors (no cardias or GEJ involvement). PDL1 positivity, defined as CPS ≥1 was found in 30.6%, using CPS ≥ 5 cutoff just 22.7% of them were positive. HER2 positivity and MMR deficiency were found in the same proportion of patients 5%. Among young patients (&lt; 50 years) 80% had diffuse histology, 30% were CPS ≥5. HER2 status and PDL1 testing was unknown in 21% and 29% respectively. Conclusions: Among these real-world patients, both HER2 and PDL1 positivity was lower than reported in other regions. Higher incidence of distal tumors, signet ring cells and diffuse histology could explain this difference. Correlation of PDL1 positivity between 22C3 and 28.8 was unknown in our population. Our study remarks the high medical need for investigation of biomarkers and developing of prospective studies for correlation and other targets like Claudins and FGFR2b.[Table: see text]
Survival of patients with microsatellite instability-high and Lynch syndrome-associated pancreatic ductal adenocarcinomas.
Authors: Naaz Nasar, Ellis Eikenboom, Kenneth Seier, Mithat Gonen, Anja Wagner, William R. Jarnagin, Jeffrey A. Drebin, Michael Ian D'Angelica, T. Peter Kingham, Vinod P. Balachandran, Kevin Soares, Manon C.W. Spaander, Alice Chia-Chi Wei
Journal: Journal of Clinical Oncology (2024)

640 Background: Pancreatic ductal adenocarcinoma (PDAC) remains a challenging disease due to its aggressive nature, late-stage diagnosis, and limited treatment options. There is an increased interest in cancers which harbor microsatellite instability (MSI) due to their susceptibility to immune checkpoint inhibitors. MSI in PDAC is rare, and little is known about survival in this subtype of pancreas cancers. Our aim was to assess overall survival in surgically resected high microsatellite instability (MSI-H), mismatch repair deficient (MMRd), and Lynch Syndrome (LS) associated PDACs treated in our center. Methods: Patients with surgically resected PDACs from 1990 to 2023 were identified. A total of 936 cases were sequenced utilizing MSK-IMPACT, a targeted next generation sequencing platform. Patients with germline or sporadic pathogenic variants or likely pathogenic variants in one of the DNA MMR genes MLH1, MSH2, MSH6, PMS2, or 3’ end of EpCAM were identified. MSI-H, MMRd, and LS-associated cases were matched to patients with microsatellite stable or MMR proficient, non-LS-associated PDAC in a 1:2 ratio with a direct match on age (±5 years), gender, and year of surgery (±3 years). Kaplan-Meier curves were used to visualize the data. A generalized estimating equation (GEE) cox model with robust sandwich estimator was used to compare matched cohorts. Results: 17 patients with MSI-H, MMRd or LS-associated surgically resected PDACs were identified. Five patients were classified as MSI-H, 3 patients were MSI-indeterminate, and 9 patients were microsatellite stable. Eight patients were found to have pathogenic germline variants in LS-associated genes. The remaining nine patients had sporadic pathogenic DNA MMR gene variants ( MLH1 n=3, MSH6 n=6). Median age at surgery was 66 (interquartile range (IQR) 60-77), 41% of the patients were female, and median year of surgery was 2014. MSI-H, MMRd or LS-associated PDACs were matched to 34 control patients. The median survival time of the cases was 12 years vs. 1.9 years in the control group. Five-year survival rate was 81% (IQR 60-100%) and 18% (7.4%-43%), respectively. LS-associated, MSI-H or MMRd status in resectable PDAC was a strong predictor of good prognosis (hazard ratio 0.17, 95% CI 0.07-0.38, p value &lt;0.001). Conclusions: MSI-H, MMRd or LS-associated PDACs displayed significantly better survival compared to their MSI-stable, MMR proficient, non-LS-associated counterparts, in the era before routine use of immunotherapy. It is expected that survival will be increased further with more frequent availability of immunotherapy.
The economic impact of short-term imaging with metastatic pancreatic ductal adenocarcinoma.
Authors: Abbey Bayless, Christina Regan, Andrew Hahn, Bethany Travis, David Hunter, Chase Irwin, Phillip Koo, Tomislav Dragovich, Michael A. Choti, Madappa N. Kundranda, John Chang
Journal: Journal of Clinical Oncology (2024)

643 Background: Although modern cancer treatment has significantly improved overall survival, this comes with a high financial cost. Based on an NIH report on Financial Burden of Cancer Care, treating pancreatic adenocarcinoma (PDAC) costs $108K, $18K, and $125K for initial treatment, during follow-up, and in last year of life, respectively. During the course of treatment, patients will visit the hospital for acute symptoms for which cross-sectional imaging is obtained within 45 days of subsequent scheduled follow-up imaging. This presents an opportunity for cost saving if data could be collected to identify an algorithm to avoid unnecessary duplication of imaging in a short interval. The purpose of this pilot study is to evaluate tumor growth trajectory within this short time span of 45 days to guide future trials to clarify the circumstances for which a subsequent follow up study is necessary. Methods: We retrospectively identified patients from our tumor registry from 2016 to 2019 who were diagnosed with metastatic PDAC (mPDAC). Subjects were included for analysis if they met the following criteria: 1) diagnosed with mPDAC; 2) had at least 2 CT abdomen/pelvis (CTAP) within 45 days of each other with one of the studies being obtained in the emergency department; and 3) had at least 1-3 measurable lesions as defined by RECIST 1.1 criteria. Tumor dimension was measured on axial images with the largest cross-section. For our primary outcome we used paired t-tests to evaluate the difference in mean size of all lesions (primary and metastatic). We also performed sub-group analyses comparing mean size of primary and metastatic lesions separately. An alpha level of 0.05 was used to determine statistical significance. Results: We screened 383 subjects from the tumor registry and identified 28 subjects suitable for our study. 18 subjects were female and 10 were male. We identified 69 target lesions, 23 of which were primary and 46 were metastatic. The mean sum of the largest dimension of target lesions was 2.82 cm on the initial study and 3.23 on the latter study (p&lt;0.001). The mean sum of the largest dimension of the primary lesion was 3.62 cm on the initial study and 3.89 on the latter study (p=0.01). For metastatic lesions, the initial sum was 2.38 cm while the latter was 2.85 (p&lt;0.001). Conclusions: Our finding of increase in tumor size in 45 days for mPDAC suggests that mPDAC is aggressive and can grow even in short time span. This suggests that if progression is identified on a study obtained within 45 days of scheduled follow-up, the follow-up study could be cancelled to avoid added cost to the patient. However, if the earlier study is stable or shows response, the scheduled follow-up may still be necessary to demonstrate continued stability/response.
Safety and efficacy of ONO-4578 plus nivolumab in metastatic colorectal cancer.
Authors: Akihito Kawazoe, Atsuo Takashima, Hiroshi Matsuoka, Yasuo Hamamoto, Tatsuya Okuno, Tetsuya Hamaguchi, Kensei Yamaguchi, Eiji Oki, Naotoshi Sugimoto, Yasushi Tsuji, Shogen Boku, Tomohiro Nishina
Journal: Journal of Clinical Oncology (2024)

93 Background: The prostaglandin E 2 -EP4 signaling is involved in immunosuppression in cancers. In the dose escalation part of the ONO-4578-01, open-label, uncontrolled phase 1 study, ONO-4578, an EP4 antagonist, plus nivolumab (4578+NIV) demonstrated manageable safety profile and antitumor activities in metastatic or advanced solid tumors. CRC cohort assessed safety, preliminary efficacy, and biomarkers of 4578+NIV in patients with metastatic colorectal cancer (mCRC). Methods: The CRC cohort was conducted at 12 sites in Japan and it included patients aged ≥20 years with mCRC; those with microsatellite-instability-high, deficient mismatch repair, or BRAF mutations were excluded. The optimal dose was determined based on the results of dose escalation part of ONO-4578-01. Patients received oral ONO-4578 (40 mg, daily) and intravenous nivolumab (480 mg, every 4 weeks) in 28-day cycles. The primary endpoint was safety. Exploratory endpoints included efficacy and biomarkers. Results: A total of 51 patients were enrolled: 24 (47.1%) were male and the median age was 59.0 (range, 33–79) years. Adverse events (AEs) occurred in 48 patients (94.1%), wherein grade 3–4 AEs occurred in 23 (45.1%). No patients died due to AEs. Serious AEs occurred in 11 (21.6%) patients. The most common AEs of any grade were rash (33.3%) and anemia (31.4%). Any-grade and grade ≥3 treatment-related AEs (TRAEs) occurred in 36 (70.6%) and 13 (25.5%) patients, respectively. Two patients achieved partial response and 18 had stable disease; the objective response rate was 3.9% (90% confidence interval [CI], 0.7–11.8) and the disease control rate was 39.2% (90% CI, 27.7–51.7). The median progression-free survival and overall survival (OS) were 1.54 (90% CI, 1.41–2.79) and 10.68 months (90% CI, 6.67–not reached [NR]), respectively. The proportion of patients continuing treatment and OS in subgroups of different PD-L1 combined positive scores (CPS) showed a tendency toward favorable efficacy in CPS-positive subgroups: the proportion of patients continuing treatment for 6 months was 4.5% (1/22) in those with CPS of 0 vs 20% (5/25) in those with CPS ≥1, and the median OS was 9.4 months (90% CI, 5.65–12.06) in those with CPS of 0 vs NR (90% CI, 10.41–NR) in those with CPS ≥1. Conclusions: 4578+NIV showed an acceptable safety profile in patients with mCRC, and no new safety signals were detected. 4578+NIV also showed antitumor activity in patients with mCRC. Favorable efficacy was observed in the PD-L1 CPS-positive subpopulation. Clinical trial information: jRCT2080223441 .
Cost-utility analysis of sequential therapy with sorafenib followed by regorafenib versus single-line therapies in advanced hepatocellular carcinoma.
Authors: Jamie Grossman, Chistopher Fawsitt, David Aceituno, Noman Paracha, Kirhan Özgürdal, Howard Thom
Journal: Journal of Clinical Oncology (2024)

529 Background: Regorafenib is the only licensed second-line therapy available for patients with advanced hepatocellular carcinoma (HCC) that progress on first-line sorafenib in the UK. We evaluated the lifetime cost-effectiveness of a sequence of treatment with sorafenib followed by regorafenib (SOR-REG) compared with licensed single-line therapies for which there is no clear sequencing options available, including atezolizumab plus bevacizumab (ATEZO+BEV), which has become the standard of care in first-line treatment, as well as lenvatinib (LEN), followed by best supportive care (BSC). Methods: Assuming a UK National Health Service and Social Services perspective, we developed a probabilistic individual-level semi-Markov model with states reflecting progression-free survival, progression following first-line treatment, further progression following second-line treatment, and death. First-line overall survival (OS) and progression free survival (PFS) were informed by fractional polynomials network meta-analysis of published trials. Individual patient data from a phase 3 trial (RESORCE) on regorafenib and BSC informed OS and PFS in the second-line setting. Costs and utilities were sourced from published studies. Cost-effectiveness was summarized using incremental net monetary benefit (INMB), which could be positive or negative depending on direction of expected benefit associated with SOR-REG, and cost-effectiveness acceptability curves at willingness-to-pay (WTP) thresholds. Results: We found 1000 probabilistic samples and 1000 patients were sufficient for convergence. Lifetime costs were highest with ATEZO-BEV ([£80,963 [95% CI: £11,022, £97,369]), followed by SOR-REG (£38,373 [£31,064, £43,420]) and LEN (£37,351 [£5,020, £55,800]). Quality-adjusted life years (QALYs) were highest with ATEZO+BEV (1.021 [0.152, 1.239), followed by SOR-REG (0.942 [0.802, 1.057]) and LEN (0.755, [0.094, 1.092]). At a WTP threshold of £30,000 / QALY gained, SOR-REG had an INMB of £40,211 (95% CI -£2,099, £52,731) and £4,589 (-£8,044, £14,481) versus ATEZO+BEV and LEN, respectively. Conclusions: A sequence of SOR-REG for patients with advanced HCC is cost-effective at WTP thresholds of £30,000 / QALY gained due to lower lifetime costs and broadly comparable QALY gains with single-line ATEZO-BEV and LEN in the UK. Broader second-line treatment options are needed for patients receiving ATEZO+BEV and LEN as first-line therapies.
FOLFOXIRI ± molecular targeting agent (bevacizumab or panitumumab) for conversion from unresectable to resectable in the advanced/recurrent colorectal cancer.
Authors: Kodai Takemori, Kazuma Kobayashi, Yusuke Inoue, Satomi Okada, Toshiyuki Adachi, Akihiko Soyama, Tomohiko Adachi, Kengo Kanetaka, Susumu Eguchi
Journal: Journal of Clinical Oncology (2024)

99 Background: As treatment for unresectable advanced/recurrent colorectal cancer (ARCC), the introduction of doublet chemotherapy, represented by FOLFOX/FOLFIRI, and molecular-targeting agents, such as anti-VEGF antibody and anti-EGFR antibody, has given ARCC patients a more than three years’ survival. Triplet chemotherapy, such as FOLFOXIRI ± Bevacizumab or Panitumumab, has already been used in daily practice. These regimens with powerful anti-tumor effects have enabled conversion from unresectable to resectable, giving patients a longer survival than those without conversion. Therefore, we explored the ideal regimen for conversion, focusing on FOLFOXIRI ± X. Methods: We retrospectively reviewed unresectable ARCC patients treated with FOLFOXIRI ± X (X:Bmab, n=24; Pmab, n=1; alone, n=2; ) between February 2015 and December 2022. The results were compared to those of patients who received other regimens (OTHERS; n=212). Results: The median overall survival (OS) was 1072 days. Forty-nine patients acquired conversion. The patients with conversion had a longer progression-free survival and OS than those without conversion (p&lt;0.0001 and &lt;0.0001, respectively). Conversion rates were 37.0% in FOLFOXIRI ± X vs. 18.4% in OTHERS (p=0.0238), while response rates were 59.3% in FOLFOXIRI ± X vs. 35.8% in OTHERS (p=0.0185). The RAS wild-type group conversion rates were 30.0% in FOLFOXIRI ± X vs. 20.6% in OTHERS, while 50.0% in FOLFOXIRI ± X vs. 15.3% in OTHERS in RAS mutant group. Anti-EGFR antibody +L-OHP-based doublet chemotherapy accounted for conversion in 35.3% of the RAS wild-type group. Anti-VEGF antibody + L-OHP based doublet chemotherapy attained 29.1% conversion rate in RAS mutant group. Molecular targeting agent+doublet or triplet regimens were essential for conversion. FOLFOXIRI ± X achieved a 88.9% disease control rate, with palliation of symptoms due to a high tumor burden in 10 of 13 cases. Conclusions: Based on these results, FOLFOXIRI ± X may be an ideal candidate for achieving conversion in first-line treatment of unresectable ARCC.
Comparing resection and stereotactic body radiation therapy for hepatocellular carcinoma with macrovascular invasion: A propensity score matched study.
Authors: Michael Yan, Zhihao Li, Pablo Muñoz-Schuffenegger, Anna Santiago, Marco Claasen, Roxana Bucur, Ian M. McGilvray, Carol-Anne Moulton, Trevor Reichman, Chaya Shwaartz, Sean P. Cleary, Grainne M. O'Kane, Robert C Grant, Tae Kim, Catherine Soo Yee Naidoo, Ali Hosni, Rebecca KS Wong, Aruz Mesci, Gonzalo Sapisochin, Laura A. Dawson
Journal: Journal of Clinical Oncology (2024)

521 Background: Macrovascular invasion (MVI) in hepatocellular carcinoma (HCC) patients is a poor prognostic factor. Current guidelines endorse systemic therapy for MVI. Local therapies present a potential for obliteration of MVI and improved survival. Surgery has been the standard local therapy at our institution, and stereotactic body radiotherapy (SBRT) has emerged as an alternative local therapy for this patient population. Methods: In this retrospective study, one-to-one optimal pair propensity score matching was used to compare outcomes of HCC patients with MVI who underwent surgery or received SBRT. Matching was done based on sex, age, ECOG, cirrhosis presence, Child-Pugh class, number of tumours, tumour volume, alpha-fetoprotein level, ALBI score, Japanese Classification of portal vein invasion, and hepatic vein invasion. Overall survival was estimated using the Kaplan-Meier method and between group differences determined using the log-rank test. The cumulative incidence of recurrence, accounting for the competing risk of death, was compared using Gray’s test. Results: Ninety of 193 patients were included after matching (45 patients in both the surgery and SBRT groups) (Table). The SBRT group had a median OS of 15 months (95% CI: 10-38), while in the surgery group it was 24 months (95% CI: 11-81). Comparing the 12-, 36-, and 60-month overall survival (OS) rates between the SBRT group (57%, 33%, 15%) and the surgery group (58%, 37%, 34%), there was no statistically significant differences (p=0.16); the 5-year OS was double in the surgical resection group. The 12-, 36-, and 60-month cumulative incidence of HCC recurrence in the SBRT group (47%, 73%, 75%) was comparable to the surgery group (69%, 69%, 69%) (p=0.89). Conclusions: Long term survival is possible in patients with HCC and MVI in a substantial minority of patients with HCC and MVI treated with local therapies. There was no statistical difference in outcomes; however, surgical resection resulted in numerically longer survival outcomes compared to SBRT after propensity score adjustment. There is rationale for investigating both local therapies with systemic therapies in future clinical trials. [Table: see text]
Impact of the COVID-19 pandemic on colorectal cancer stage at presentation.
Authors: Malcolm Hart Squires, Nicole Lindolm, Reilly Shea, Erin E. Donahue, Michelle Wallander, Jonathan C. Salo
Journal: Journal of Clinical Oncology (2024)

80 Background: The primary study objective was to assess the impact of COVID-19 on the stage at presentation for patients with newly diagnosed colorectal cancer treated within a large cancer center network. Additionally, we aimed to evaluate differences in pathologic stage and treatment modality for patients diagnosed with colorectal cancer both immediately before and during the height of the COVID-19 pandemic. Methods: A retrospective analysis was performed on all subjects newly diagnosed with colorectal cancer between January 2019 and April 2021 at Levine Cancer Institute. Patients had a primary diagnosis of adenocarcinoma of the colon, rectum, or appendix. Patients were categorized into two cohorts based on date of diagnosis, with the pre-COVID-19 group diagnosed between January 2019 and February 2020 and the COVID-19 group diagnosed between March 2020 and April 2021. Chi-squared tests were used to evaluate the association between COVID-19 group and stage at presentation as well as pathologic stage. Results: A total of 1,190 patients were diagnosed with colorectal cancer within the study timeframe. Of the 613 patients diagnosed pre-COVID-19, 159 (25.9%) had metastatic disease at initial presentation. Comparatively, 577 patients were diagnosed during the COVID-19 study period, with 143 (24.8%) presenting with metastatic disease (p = 0.65).Of the 888 patients who presented with non-metastatic disease, 770 underwent primary surgical intervention for the initial treatment of their cancer, with 396 (87.2%) pre-COVID-19 and 374 (86.2%) COVID-19 patients receiving surgery (p = 0.65). Likewise, no significant difference was observed for T-classification, N-classification, or overall pathologic stage among patients undergoing surgical resection between the pre-COVID-19 and COVID-19 groups (p = 0.20; Table). Furthermore, amongst patients who presented with non-metastatic disease, chemotherapy was utilized for 200 (44.1%) patients diagnosed pre-COVID-19 and 190 (43.8%) patients diagnosed during COVID-19 (p = 0.93). Conclusions: We did not observe a significant difference in the proportion of patients presenting with metastatic colorectal cancer during COVID-19 versus those presenting pre-COVID-19. Furthermore, there was no significant difference observed among non-metastatic patients between the two groups for rates of initial surgical resection, pathologic stage, and treatment with chemotherapy. [Table: see text]