tbuckley/cabot-search huggingface dataset:
Esophageal cancer in Hispanics: A propensity score matched analysis of the National Cancer Database.
Authors: Kenneth Lee Meredith, Jamie Huston, Ravi Shridhar
Journal: Journal of Clinical Oncology (2024)

258 Background: Hispanics are the fastest-growing minority and largest ethnic group accounting for 19.1% of the US population. The American Cancer Society estimated 21,560 new cases of esophageal cancer (EC) in the US in 2023. Hispanics are reported to be at high risks for EC. We sought to interrogate the demographic patterns of esophageal cancer in Hispanics. Additionally, we sought to examine evidence of socioeconomic disparities and differential therapy. Methods: We identified Hispanic vs Non-Hispanic (NH) patients in the National Cancer Database with esophageal cancer between 2005–2018. Variables compared were age, sex, tumor data, surgical intervention, type of treatment, insurance status, income, residence area, and Charlson/Deyo score. Pearson’s Chi-square test was used to compare categorical variables. Groups were statically equated with propensity score-matched analysis (PSM). Survival analysis was estimated by the Kaplan-Meier method and associated log-rank test. Significance was considered at p-value ≤0.05. Results: We identified 66,335 patients with a median age of 63 years (18-90). Hispanics represented 4.2% (2,786) of the entire patient cohort. In this US population we identified significant disparities between Hispanic and NH groups. Differences among Hispanics included higher prevalence of squamous EC (22% vs 19%) p&lt;0.001, higher likelihood of stage IV disease (40.7% vs. 34.8%) p&lt;0.001, younger age p&lt;0.001, higher uninsured status (10.3% vs 3.3%) with income &lt; $40,227 (27.5% vs 16.9%) p&lt;0.001 when compared to NH. However, Hispanics were less likely to have surgical intervention (20.5% vs 27.5%) p&lt;0.001, receive neoadjuvant therapy (61.8% vs 72%) and overall, less likely to receive any type of treatment (30.1% vs 26.1%) when compared to NH p&lt;0.001. Time to treatment was delayed in those Hispanics who were uninsured 37 weeks (22-55) compared to those with private insurance 31 weeks (20-47) p&lt;0.001. Multivariate analysis revealed that any treatment, insurance status, and lower income were all predictors of survival. Treated Hispanics demonstrated no difference in survival then their treated non-Hispanic counterparts (median survival 18.5 vs 18.7 months) with overall 5 year survival at 24% and 25% respectively (p=0.66). Conclusions: Despite lower prevalence, there is a disproportionately higher number of metastatic and untreated cases of esophageal cancer among Hispanics. This disparity may be explained by Hispanics' limited access to medical care exacerbated by their socioeconomic and insurance status. Our findings warrant further clinical and epidemiologic research to reveal other factors impacting these health and health care disparities.
The efficacy and safety of conversion therapy after initial systemic chemotherapy in advanced esophageal cancer with distant metastases: A multicenter retrospective observational study.
Authors: Takayuki Tsuji, Satoru Matsuda, Yuta Sato, Koji Tanaka, Yusuke Tsuruta, Masaya Watanabe, Yoichi Hamai, Motomi Nasu, Zenichiro Saze, Yuichiro Nakashima, Motoo Nomura, Shun Yamamoto, Eisuke Booka, Koshiro Ishiyama, Takeo Bamba, Katsuyuki Sakanaka, Takahiro Tsushima, HIROYA TAKEUCHI, Ken Kato, Hirofumi Kawakubo
Journal: Journal of Clinical Oncology (2024)

310 Background: Systemic chemotherapy, with or without radiation, has been the standard treatment for esophageal squamous cell carcinoma (ESCC) with distant metastasis. The increased efficacy of multimodality treatment allows for the consideration of conversion therapy with curative intent for initially unresectable ESCC after initial treatment. In the present study, we examined the safety and effectiveness of conversion therapy for ESCC. Methods: Conversion therapy was defined as surgery or chemoradiation therapy (CRT) aiming at cure after initial treatment for tumors that were initially unresectable due to distant metastasis. The patients who underwent conversion therapy for ESCC between 2011 and 2021 at participating institutions were retrospectively reviewed. Patient backgrounds, treatment outcomes, and overall survival (OS) were evaluated. Results: From 22 institutions, 149 patients were enrolled. As defined, all patients received systemic chemotherapy as an initial treatment. The distant metastatic sites in para-aortic lymph nodes/extra regional mediastinal lymph nodes/lung/liver/bone/others were 81(54%)/19 (13%)/14 (9%)/11 (7%)/4 (3%)/20 (14%), respectively. After the initial treatment, 116 patients underwent surgery and 33 patients received CRT as conversion therapy. Of 116 patients who underwent conversion surgery, the incidence rate of postoperative pneumonia/leakage/recurrent laryngeal nerve palsy was 16%/7%/6%, respectively. R0 resection was obtained in 87%. Regarding the non-hematological toxicities during conversion CRT (CTCAE grade 3 or higher), decreased appetite/dysphagia/esophagitis was 21%/15%/9%, respectively. No grade 4 or higher hematologic toxicities were observed. The 3-year OS (3y-OS) rate for all patients was 41.9%; no significant differences were found between surgery and CRT groups (43.3% vs 37.0%, p = 0.112). Pathological responders showed a significantly longer OS than non-responders (3y-OS, 56.4% vs 36.1%, p = 0.010). The distribution or number of distant metastases were not identified as prognostic factors. Conclusions: This study showed that conversion therapy for ESCC patients with distant metastasis could be conducted safely and have a favorable prognosis. Since its survival benefit would depend on the pathological response, it is important to develop an indicator to predict pathological response before surgery and carefully select appropriate candidates of conversion therapy in ESCC.
Does metformin use effect overall survival for patients with pancreatic cancer?
Authors: Ravi Ramjeesingh, Samina Nazarali, Margaret Sheridan, Peiran Sun, Aimee Popovacki
Journal: Journal of Clinical Oncology (2024)

660 Background: In Canada, the incidence of pancreatic cancer ranks 11 th amongst all cancers but has resulted in the third highest mortality. Despite advancements in both diagnostics and therapeutics, the 5-year overall survival rate of pancreatic adenocarcinoma (PDAC) remains under 10%. Emerging studies have begun to examine the role of the hypoglycemic medication metformin, in improving outcomes of patients with PDAC. In cell cultures, metformin has been shown to have direct growth-inhibitory actions on malignant cells, and previous retrospective studies have suggested a potential association between metformin use and increased overall survival in breast and prostate cancer. To identify if metformin plays a role in improving PDAC outcomes, we have conducted a retrospective review of PDAC in Nova Scotia, Canada. Methods: We conduced a retrospective study of 630 patients diagnosed with PDAC treated at the Halifax Infirmary (Halifax, Nova Scotia). Records of patients were reviewed and information regarding patient demographics, cancer staging, metformin use, date of diagnosis, and date of death were collected. Statistical analysis using the log rank method was done to determine if there was a statistically significant difference in overall survival between groups. Results: Among the 630 patients identified, there were 337 males and 293 females. The average age at time of diagnosis was 74.02 years. There was no significant difference found in overall survival of patients on metformin (n=132, mean overall survival (mOS) 6.68 months), compared to those not on metformin (n=498, average survival 7.44 months), p=0.989. Further subgroup analysis based on cancer staging showed that patients with resectable pancreatic cancer (AJCC stage I-IIA, n=140), who did not use metformin (n=106) had a mOS of 12.98 months compared to 9.71 months for metformin users (n=34), p=0.438. For patients with locally advanced disease (AJCC stage IIB-III, n=125), the average mOS of non-metformin users (n=103) was 11.10 months compared to 10.73 months for metformin users (n=22), p=0.803. For patients with metastatic disease (AJCC stage IV, n=365), the average survival of non-metformin users (n=289) was 3.48 months compared to 4.26 months for metformin users (n=76), p=0.803. Diabetic patients (n=195) on metformin (n=132) compared to those not on metformin (n=63), did not show significant survival difference (mOS 6.68 months vs 6.61 months respectively, p =0.602). Conclusions: Despite suggestion that metformin use may improve survival in some cancers, we found no statistical improvement in mOS for metformin use in PDAC patients. Future research including a prospective study should be undertaken to confirm these results in a larger sample size.
BOLD-100-001 (TRIO039): A phase 2 study of BOLD-100 in combination with FOLFOX in patients with advanced mCRC previously treated with FOLFOX/CAPOX—Efficacy and safety analysis.
Authors: Jennifer L. Spratlin, Grainne M. O'Kane, Do-Youn Oh, Sun Young Rha, Elaine McWhirter, Elena Elimova, Petr Kavan, Moon Ki Choi, Dae Won Kim, Rachel Anne Goodwin, J. Randolph Hecht, Seung Tae Kim, Dong-Hoe Koo, Khalif Halani, E. Russell McAllister, Michelle Jones, Malcolm Snow, Yasmin Lemmerick, Gonzalo Spera, Jim Pankovich
Journal: Journal of Clinical Oncology (2024)

143 Background: BOLD-100 is a first-in-class metallotherapeutic with a unique multimodal mechanism of action currently in phase 2 clinical development for the treatment of advanced gastrointestinal cancers. Standard treatment options for patients (pts) with metastatic colorectal cancer (mCRC) include FOLFOX or CAPOX in first or second line therapy. This study explored the benefit of BOLD-100 + FOLFOX in previously treated mCRC patients. Methods: This prospective, phase 2 study evaluates BOLD-100 + FOLFOX in pts with mCRC. All pts received prior standard treatment, including FOLFOX or CAPOX. Pts received 625 mg/m2 of BOLD-100 + FOLFOX on day 1 of each 14-day cycle and treated until progressive disease or unacceptable toxicity. The primary objective is to evaluate PFS, OS, and ORR in treated patients. Disease Control Rate (DCR) was also determined. Results: As of 31Aug2023, 36 pts with advanced mCRC were treated. Median age was 62 years (range 40-78), 56% were women, all pts were ECOG 0 (25%) or 1 (75%). Enrolled pts had a median of 4 prior systemic therapies, including FOLFOX/CAPOX. All but one patient had stage IV disease. On study, pts received a median of 6 cycles of BOLD-100 + FOLFOX [range 1-17]. Five pts remain on treatment with 19 in follow-up. Median PFS was 3.9 [2.7, 5.7] months, median OS 9.6 [6.0, 17] months, ORR 7% [1,20] and DCR 76% [58, 88] in the 29 evaluable pts. Two pts achieved a partial response, and 2 pts had target tumor lesion decreases between 20-29%. Study treatment was well tolerated. Of the 36 treated pts, 33 had 1 or more treatment-emergent adverse events (AEs), most common neutropenia (n=17, 47%), nausea (n=15, 42%), vomiting (n=8, 22%), fatigue (n=7, 19%), infusion related reaction (n=7, 19%), and pruritus (n=6, 17%). Most related AEs were grade (G) 1-2. 15 pts (42%) had G3/4 neutropenia. Despite previous oxaliplatin treatment, fewer than 6% of pts reported peripheral neuropathy or peripheral sensory neuropathy and all were G1/2. Conclusions: BOLD-100 + FOLFOX is an active and well-tolerated treatment in this heavily pre-treated Stage IV mCRC study population. There were no new safety signals. The mPFS, mOS, ORR and DCR data demonstrate significant clinical benefit and improvement over the currently available therapies, with minimal treatment emergent neuropathy or significant toxicities. This promising treatment combination should be further studied. Clinical trial information: NCT04421820 .
Epidemiological characteristics of patients with pancreatic cancer with and without diabetes mellitus: A retrospective cohort study.
Authors: Sarah Elizabeth Eichinger, Alejandro Nieto Dominguez, Daniel Guifarro Rivera, Ekrem Turk, Chun-Wei Pan
Journal: Journal of Clinical Oncology (2024)

705 Background: Pancreatic cancer accounts for approximately 3% of new cancers diagnosed in the US and more than 8% of all cancer deaths. Despite the increasing incidence, there are few indicated screenings, mostly in patients with genetic mutations. Pancreatic cancer is associated with several risk factors including tobacco use, family history, heavy alcohol use, and diabetes mellitus (DM). In the US, more than 11% of adults have a diagnosis of diabetes and incidence is projected to rise over the coming years. Given the risk of DM associated with pancreatic cancer, establishing preventative measures, early intervention, and appropriate follow up for diabetic control could be an important step in decreasing the risk of pancreatic cancer. This study examines the demographic characteristics of patients with a diagnosis of pancreatic cancer with and without DM. Methods: We used the 2016-2019 Nationwide Inpatient Sample database, the largest all-payer inpatient care database in the US, to stratify all patients admitted with a diagnosis of pancreatic cancer, with and without DM, to further characterize their epidemiological characteristics. Results: Characteristics of patients with and without DM and pancreatic cancer are shown in the table. There were 150,275 patients diagnosed with pancreatic cancer, of which 44,170 (29%) had a concomitant diagnosis of DM. Of patients with both pancreatic cancer and DM, 53% were women (51% in patients without DM), 64% were white (70% in patients without diabetes), and 63% had Medicare for insurance (60% in patients without DM). Conclusions: Of patients with pancreatic cancer 29% had a concomitant diagnosis of DM(p=0.00). Epidemiological characteristics of patients with pancreatic cancers with and without DM such as age, sex, and insurance status were similar between both groups. However, there was a decreased percentage of Caucasian patients with pancreatic cancer and DM compared to those without DM. Given the association of diabetes with pancreatic cancer, and rising incidence of patients with diabetes in the US, emphasis on diabetes prevention and control may be an important factor in reducing the incidence pancreatic cancer. This study also suggests the need for further research to determine if there is utility in screening for pancreatic cancer in patients with diabetes to decrease the burden of pancreatic cancer in the US population.[Table: see text]
Real-world analysis of patient characteristics and outcomes among patients with metastatic colorectal cancer receiving trifluridine/tipiracil (FTD/TPI) plus bevacizumab versus FTD/TPI monotherapy.
Authors: Joleen M. Hubbard, Lulu K. Lee, Jay L. Grisolano, Kacper Perkowski, Tehseen Salimi, Reza Kazerooni, Robert S. Epstein
Journal: Journal of Clinical Oncology (2024)

34 Background: Trifluridine/tipiracil (FTD/TPI) is a standard of care therapy for patients with refractory metastatic colorectal cancer (mCRC). Recently, FTD/TPI in combination with bevacizumab (BEV) was also approved in this setting based on outcomes from the phase 3 SUNLIGHT trial, including statistically significant improvements in overall survival (OS) compared with FTD/TPI. This study examined demographic/clinical characteristics, treatment duration, OS, and healthcare resource use (HCRU), including outpatient/emergency room (ER) visits and hospitalizations, among patients with mCRC receiving FTD/TPI+BEV versus FTD/TPI in a real-world setting. Methods: This was a retrospective study of adults with CRC, who initiated FTD/TPI as monotherapy or in combination with BEV, identified from the Cerner Enviza electronic health records (EHR) database (12/2020–06/2023). A manual chart review of patients’ medical records was conducted where last follow-up was defined as death or last encounter in the EHR. Descriptive statistics were reported for all study variables; Kaplan Meier curves were used to estimate OS. Results: Of 197 patients abstracted, 122 (62%) received FTD/TPI+BEV combination therapy and 75 (38%) FTD/TPI monotherapy. Mean age was similar between the FTD/TPI+BEV and FTD/TPI groups (60.2 y vs 61.8 y) and 66% vs 63%, respectively, were male. Mean Charlson Comorbidity Index was 8.9 for the FTD/TPI+BEV group vs 8.5 for the FTD/TPI group and body mass index was 26.9 kg/m 2 vs 27.3 kg/m 2 , respectively. Most patients received treatment in the third or fourth line (65% FTD/TPI+BEV; 75% FTD/TPI). Median follow-up was 5.3 and 4.6 mo, respectively. Mean duration of treatment was 3.7 vs 2.7 mo for FTD/TPI+BEV vs FTD/TPI monotherapy (Table). Median OS (from FTD/TPI initiation to death) was 11.5 and 9.6 mo for FTD/TPI+BEV and FTD/TPI groups (number of deaths: 38 and 22), respectively. Patients receiving FTD/TPI+BEV had numerically more outpatient visits (20.5 vs 13.9), but similar ER visits (0.5 each) and slightly fewer hospitalizations (1.1 vs 1.2) compared with FTD/TPI, during follow-up. Overall HCRU costs were similar between groups (27,175 vs 27,891). Conclusions: This real-world study supports the value of FTD/TPI+BEV combination therapy vs FTD/TPI monotherapy as seen in the SUNLIGHT trial. Patients with FTDTPI+BEV were treated for longer duration with improved OS and no difference in trends for HCRU and associated costs. [Table: see text]
The implication of failure patterns after neoadjuvant chemoradiotherapy with small involved-field in esophageal squamous cell carcinoma.
Authors: Hyunju Shin, Dongryul Oh, Jae Myoung Noh, Kyungmi Yang
Journal: Journal of Clinical Oncology (2024)

376 Background: In this study, we aimed to analyze failure patterns, the clinical and biological prognostic factors for treatment outcomes, and evaluate the feasibility of involved-field irradiation (IFI) in patients with esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant chemoradiotherapy (CCRT). Methods: We retrospectively reviewed the medical records of 511 patients diagnosed with ESCC and underwent neoadjuvant CCRT and radical esophagectomy between January 2016 and February 2022 at Samsung Medical Center. For IFI, the clinical target volume (CTV) was defined as the primary gross tumor volume (GTV) plus a 2.0-3.0 cm longitudinal margin and a 0.5-1.0 cm circumferential margin, as well as the GTV of lymph nodes (LN) plus a 0.5-1.0 cm margin. For elective nodal irradiation (ENI), the CTV encompassed supraclavicular, mediastinal, or abdominal LN regions based on the primary tumor location. IFI was applied in most cases (98%). The failure patterns, loco-regional control (LRC), and survival outcome were analyzed. Regional lymph nodes (LNs) were defined and classified according to the AJCC 8th edition. Non-regional LNs were defined as metastatic LNs in neck, thorax, abdominal area except regional LNs. Results: With a median follow-up of 44.4 months, 213 (41.7%) patients experienced recurrence. The first recurrent sites were locoregional (LR) in 98 patients (19.2%), non-regional LN in 81 (15.9%), and distant organs in 152 (29.7%). Among the 98 patients with LR recurrence, RT in-field failure occurred in 53 (10.4%) patients, in &amp; out-field failure in 18 (3.5%), and out-field failure in 27 (5.3%). In 27 cases of out-field failure only, LR recurrent lesion could be included in the target volume in 7 (1.4%) cases if ENIs were applied. Among the 27 patients, 10 received salvage treatment and 2 did not experience further recurrence. The analysis for the detailed LN recurrence showed that the upper mediastinal and supraclavicular LNs were the most frequent area, regardless of the primary tumor location and other clinical factors. Among 213 recurrent cases, 54 (10.5%) recurred in upper paratracheal LN and 40 (7.8%) in supraclavicular LN. The 5-year LRC rates, disease-control rates, and overall survival (OS) rates were 77.5%, 53%, and 54.3%, respectively. Multivariate analysis revealed that gender, age, cStage, ypStage, and resection margin status were independent prognostic factors for OS. Conclusions: Neoadjuvant CCRT using IFI with a small margin showed favorable treatment outcomes and out-field recurrence that the traditional ENI field could cover accounted for a small portion; thus, it might be feasible in the neoadjuvant setting. However, we need to consider that the upper mediastinal and supraclavicular areas were the most frequent recurrence sites.
Impact of <i>KRAS</i> codon-specific mutations on survival of patients with metastatic CRC (mCRC) treated with trifluridine-tipiracil (TAS) plus bevacizumab (Bev): A real-world analysis.
Authors: Giulia Maddalena, Ymke van der Pol, Zachary Rivers, Arvind Dasari, Jane E. Rogers, Justin Guinney, Scott Kopetz, Kanwal Pratap Singh Raghav
Journal: Journal of Clinical Oncology (2024)

201 Background: Clinical benefit and survival data utilizing later lines of therapy with TAS in metastatic CRC is limited, highlighting the need for better patient selection (Mayer, NEJM 2015). Recently, codon-specific KRAS mutations have been implicated as biomarkers for TAS treatment. KRAS G12 was associated with a lack of benefit and G13 displayed improved benefit (Van de Haar, Nat Med 2023) However, it is unknown whether this differential prognostic impact occurs on TAS + Bev which has now supplanted TAS as the standard of care (Prager, NEJM 2023). Methods: We retrospectively investigated outcomes in a cohort of 100 mCRC patients treated with TAS + Bev for ≥1 month between September 2019 and April 2023 at MD Anderson (cohort A) using institutional databases. For validation, a cohort of 205 mCRC patients from the Tempus database was used (cohort B). Mutation status was determined from tissue biopsy using clinical NGS (Beaubier, Nat Biotechnol 2019). The primary endpoint was overall survival (OS), determined by Kaplan Meier estimators and risk set adjustment methods and compared using the log-rank test. Results: Baseline characteristics were similar in the two cohorts; in cohort A, 52% (N = 52) patients were male and median age at diagnosis was 56 years (IQR:47-61y). Correspondingly, 56% (N = 93) of cohort B were male and the median age at diagnosis was 56 (IQR: 47-66y). The table shows the distribution of codon-specific RAS mutations and their OS across the two cohorts. Comparative analysis of median OS (mOS) between KRAS G12, KRAS G13 and RAS/RAF-WT subgroups showed no significant differences (p=0.06 and 0.94 for cohort A and B, respectively). Conclusions: In this cohort of mCRC treated with TAS-Bev, codon-specific KRAS mutations did not appear to predict survival benefit, unlike previously reported for TAS treated patients. Overall, KRAS G13 mutated patients appeared to have a worse outcome. Further investigations into codon-specific impact are required prior to incorporating this for patient selection for treatment. *G. Maddalena and Y. van der Pol as co-first authors. [Table: see text]