tbuckley/cabot-search huggingface dataset:
Epidemiological characteristics of gastric and pancreatic cancers in Latin America: The LACOG 0222 GASPAR study.
Authors: Renata D'Alpino Peixoto, Diogo Bugano Diniz Gomes, Victor Hugo Fonseca Jesus, Rui Fernando Weschenfelder, Antonio Soares Dias Jr, Anelisa Kruschewsky Coutinho Araujo, Rafaela Gomes de Jesus, Matheus Soares Rocha, Gustavo Cartaxo de Lima Gössling
Journal: Journal of Clinical Oncology (2024)

TPS710 Background: Gastric and pancreatic tumors remain among the cancers with the poorest prognoses in both high and low/middle-income countries. Data on the clinicopathological characteristics, standard treatments, and outcomes of these tumors are scarce in Latin America. This study is the first comprehensive effort to report epidemiological and clinical data in this region. Methods: The LACOG 0222 GASPAR trial ( NCT05924789 ) is a retrospective and prospective (bidirectional) observational cohort study. Enrollment of 200 patients across 15 sites in Latin America is planned, 120 patients in cohort A (gastric cancer) and 80 patients in cohort B (pancreatic cancer). No interventions are proposed. Eligibility criteria include age ≥18 years, histological diagnosis of gastric and gastroesophageal junction cancer (cohort A) or pancreatic cancer (cohort B), advanced disease diagnosis since January 2019, and availability of adequate medical data for data collection. The primary objective is to describe the clinical characteristics, treatment patterns, and outcomes of patients with gastric and pancreatic cancer in Latin America. Data on patients’ clinical characteristics, demographics, tumor pathological features, surgical therapy, radiotherapy, chemotherapy, and target therapy will be collected. Patient outcomes, such as recurrence-free survival, progression-free survival, and overall survival will also be collected. Patients will be followed up for up to 3 years after diagnosis. No a priori sample-size calculations were performed. The demographic and underlying disease characteristics will be evaluated using descriptive statistics. Time-to-event outcomes (disease-free survival, progression-free survival, and overall survival) will be estimated using the Kaplan-Meier method. From August 2023 to September 2023, 34 pts were included. The target accrual is expected to be completed by February 2024. The results are expected to be presented in August 2024.
A randomized phase III study comparing 2-weekly docetaxel, cisplatin and 5-FU (bDCF) with cisplatin and 5-FU (CF) in patients with metastatic or recurrent esophageal cancer: JCOG1314 (MIRACLE).
Authors: Takahiro Tsushima, Shuichi Hironaka, Yasuhiro Tsubosa, Ken Kato, Motoo Nomura, Hiroki Hara, Yuko Kitagawa, Kazuo Koyanagi, Takeshi Kajiwara, Naoki Takegawa, Hisahiro Matsubara, Hideo Baba, Masaru Morita, Toru Masuzawa, Hiroko Hasegawa, Takashi Kojima, Ryunosuke Machida, Keita Sasaki, HIROYA TAKEUCHI, Shigenori Kadowaki
Journal: Journal of Clinical Oncology (2024)

322 Background: For metastatic or recurrent esophageal cancer, 2-drug combination of cisplatin and 5-FU (CF) has long been a standard of care before the emergence of immune checkpoint inhibitors (ICIs). Previous phase I/II study of 3-drug combination, 2-weekly docetaxel plus CF (bDCF) showed promising antitumor activity (JCOG0807). We conducted JCOG1314, a randomized phase III study to confirm the survival superiority of bDCF over CF. Methods: Main eligibility criteria were metastatic or recurrent esophageal cancer; histologically proven squamous cell carcinoma or adenocarcinoma; age 20 to 75; no previous systemic therapy for metastatic disease. Patients were randomly assigned to CF arm (cisplatin 80 mg/m 2 on day 1, and 5-FU 800 mg/m 2 on days 1-5, every 28 days), or bDCF arm (docetaxel 30 mg/m 2 on day 1 and day 15 in addition to CF, every 28 days). The primary endpoint was overall survival (OS). To detect a 3-month difference in median OS [hazard ratio (HR) = 0.73] with study-wise, one-sided alpha level of 5% and power of 75%, 240 patients were required. Results: A total of 240 patients were randomly assigned to bDCF (n = 121) and CF (n = 119) between September 2014 to April 2021. Patient background in bDCF/CF arm was median age, 65/64 years; ECOG performance status 0, 69%/75%; metastatic disease, 63%/67%, ≥2 metastatic organs, 59%/56%; squamous cell carcinoma, 94%/97%. As a data cut-off of April 2023, all 240 patients discontinued protocol treatment. The reasons for treatment discontinuation in bDCF/CF arm were disease progression, 58%/71%; adverse events (AEs), 35%/27%; refusal, 1%/1%; others, 7%/5%, respectively. With a median follow-up of 15.3 months (m), bDCF arm was not superior to CF arm in terms of OS with a median of 16.2 m versus 14.8 m [HR, 0.90; 95% confidence interval (CI), 0.68–1.19; p = 0.23], however, progression-free survival (PFS) in bDCF arm was favorable compared to CF arm with a median of 6.0 m versus 5.2 m (HR, 0.68; 95% CI, 0.52–0.88). Response rate in bDCF/CF arm was 52.8%/45.6%. Major grade 3 or 4 AEs observed in bDCF/CF arm were neutropenia (37.8%/27.1%); anorexia (25.2%/16.1%); fatigue (10.1%/15.3%); hyponatremia (13.4%/13.6%). No treatment related death was observed. Subsequent therapy in bDCF/CF arm was provided for 87%/89% of patients. Conclusions: JCOG1314 did not reach its primary objective, although bDCF was associated with significant increases in PFS. CF is still the standard therapy in patients with metastatic or recurrent esophageal cancer if ICIs are not applicable. Clinical trial information: jRCTs031180143 .
Clinical outcomes of argon plasma coagulation for the treatment of gastric low-grade dysplasia.
Authors: Hoyoung Wang, Kee Don Choi, Jin Hee Noh, Hee Kyong Na, Kee Wook Jung, Ji Yong Ahn, Jeong Hoon Lee, Do Hoon Kim, Ho June Song, Gin Hyug Lee, Hwoon-Yong Jung
Journal: Journal of Clinical Oncology (2024)

336 Background: Argon plasma coagulation (APC) could be considered a treatment modality for small gastric low-grade dysplasia (LGD) instead of endoscopic resection (ER). Our study investigated the clinical outcomes of APC for treating gastric LGD and associated variables with local recurrence. Methods: This study included 911 patients who underwent APC for gastric neoplasms at the tertiary hospital from July 2007 to March 2022 with a minimal follow-up of 12 months. 112 subjects without any information about H. pylori infection status, 164 subjects who underwent APC for salvage therapy, 5 subjects with high grade dysplasia, and 12 subjects with cancer were excluded. Through a retrospective review of medical data, the clinical outcomes and variables associated with the local recurrence were analyzed. Results: A total of 618 patients with LGD (median age of 64 years old) were followed up for a median of 30 months and local recurrence has happened in 21 patients (3.4%). Multivariate analysis showed lesion size (hazard ratio 1.06, 95% confidential interval 1.01–1.12) was associated with the local recurrence. Among 557 lesions smaller than 10 mm, local recurrence was found in 14 cases (2.6%) and local recurrence was in 7 cases (9.5%) of 109 tumors larger than 10 mm ( p &lt;0.004). Conclusions: In gastric LGD smaller than 10 mm without scars, APC is a good treatment modality in place of ER. However, when a lesion is larger, APC should be selected carefully with close monitoring. [Table: see text]
Genomic profile and clinical feature of esophageal squamous cell carcinoma, focusing on MSI, TMB, and HRD status: Analysis with the national database of Japan.
Authors: Ryuichi Morita, Takeshi Ishikawa, Toshifumi Doi, Junichiro Itani, Daiki Sone, Masahiro Iwasaku, Hirotaka Konishi, Atsushi Shiozaki, Hitoshi Fujiwara, Hideyuki Konishi, Koichi Takayama, Yoshito Itoh
Journal: Journal of Clinical Oncology (2024)

412 Background: In Japan, cancer genome profiling (CGP) testing has been widely used from 2019, and genomic and clinical information integrated into national database (C-CAT database) is now available for secondary use for innovative research. In esophageal squamous cell carcinoma (ESCC), more than 500 patients (as of December 2022) have already undergone CGP testing. MSI-H and TMB-H ESCC are rare, and information is lacking. Using C-CAT data base, we analyzed the clinical and genomic characteristics of ESCC, especially focusing on MSI, TMB, and HRD status. Methods: We retrospectively reviewed data on 535 cases with ESCC enrolled in C-CAT between June 2019 and December 2022. The clinical features, genomic variants classified as oncogenic/pathogenic, MSI/TMB status and response to treatment (response rate; RR and time to treatment failure; TTF) were evaluated. Results: Oncogenic/pathogenic variants were detected in 527 cases (98%), and the Top 5 gene mutations were TP53 (94.6%), CDKN2A (56.6%), CDKN2B (43.7%), CCND1 (42.6%), and FGF19 (38.9%), in order of prevalence. No patient had MSI-H, and number of patients with TMB-H (≥10 Muts/Mb) and HRD were 82 (15%) and 15 (13%), respectively. Regarding the efficacy of first-line chemotherapy (IO-containing regimen in 5 cases, 0.9 %), the TTF was significantly shorter in TMB-H cases than in TMB-L cases (11.8 vs 17.5 weeks, p=0.006). No difference in response to anti-PD-1 antibody was observed depending on TMB status (RR, TMB-L 19 % vs. TMB-H 12 %). Patients with BRCA1/2 mutations tended to respond better to first-line chemotherapy including platinum drugs, although there was no difference in response to treatment with or without other HRR mutations. The percentages of cases delivered new treatments based on CGP testing was 6.8%. The percentage of cases with HRD or TMB-H suggested new treatment based on GCP testing was significantly higher than those without them. Conclusions: Patients with BRCA1/2 mutations are more sensitive to platinum combination chemotherapy and may be good candidates for PARP inhibitors in ESCC. Since TMB-H patients are resistant to standard chemotherapies, we should promote the development of immunotherapy and molecular-based targeted therapies for this population.
Survival and progression-free survival in patients undergoing curative resection for intrahepatic cholangiocarcinoma.
Authors: Nazli Begum Ozturk, Laith H. Jamil
Journal: Journal of Clinical Oncology (2024)

562 Background: Intrahepatic cholangiocarcinoma (iCCA) is a relatively rare but increasingly prevalent form of primary liver cancer. Surgical resection with negative margins is the mainstay of the treatment for patients with resectable-iCCA. However, given the rarity of iCCA and its low resectability rate, well-defined prognostic markers and outcomes for patients undergoing curative hepatectomy are lacking. We aimed to analyze the characteristics and outcomes of patients undergoing liver resection for iCCA. Methods: All consecutive patients with confirmed iCCA who underwent hepatectomy between 7/2006-3/2023 at our institution were included. Patients who received neoadjuvant therapy were excluded. Demographic, clinical, radiological, histopathological, recurrence, and survival data were collected. Overall survival was calculated from the date of liver resection to the date of death or last clinical encounter. Continuous variables are reported as median and interquartile range (IQR) 1 and IQR3, and categorical variables as counts and percentages. Results: A total of 83 patients (43 male, 40 female) were included in the final analysis. The median age at resection was 67 years (58.0-74.0). Histologically proven liver disease was present in 30.12% and liver cirrhosis was present in 9.63% of patients. Among all patients, hypertension was present in 61.44%, diabetes mellitus in 25.30%, inflammatory bowel disease in 7.22%. The median tumor size was 4.4 cm (3.0-6.2). Tumor histologic grade was 55.42% moderately differentiated tumor, 37.3% poorly differentiated tumor, and 7.22% well differentiated tumor. Of all patients, 37.66% had lymph node invasion, 35.61% had perineural invasion, and 30.76% had vascular invasion on liver histology. Positive surgical margins were present in 20.73% of patients. The duration from liver resection to the last follow-up or death was 1.6 years (0.80-3.20). The 1-, 3-, and 5-year recurrence-free survival rates were 72.78, 34.95, and 15.88% respectively. The 1-, 3-, and 5-year overall survival rates were 90.9%, 65.9, 44.2%, respectively. Advanced iCCA stage at diagnosis ( p&lt;0.001), presence of lymph node metastasis ( p=0.03), vascular invasion ( p=0.02), and age&lt;50 ( p=0.01) were associated with significantly worse overall survival. There was no statistically significant survival difference between patients with concurrent liver disease and those without (6.88 vs 4.35 years, p=0.46.). Conclusions: Our results demonstrate that iCCA carries a substantial risk of recurrence despite curative resection. The presence of advanced stage at diagnosis, lymph node involvement, vascular invasion, and age&lt;50 were associated with significantly worse overall survival. Liver disease had no significant effect on the survival outcomes. Predictive markers of recurrence and survival in patients vary in the literature and remain to be validated.
Inter-reader variability of imaging biomarkers for therapeutic response in pancreatic ductal adenocarcinoma.
Authors: Jon Stanley Heiselman, Natally Horvat, Burcin Agridag-Upcinar, Onur Yildirim, Brett Logan Ecker, Eileen Mary O'Reilly, Jeffrey A. Drebin, Vinod P. Balachandran, T. Peter Kingham, Michael Ian D'Angelica, Kevin Soares, Richard K. G. Do, Maria El Homsi, William R. Jarnagin, Alice Chia-Chi Wei, Jayasree Chakraborty
Journal: Journal of Clinical Oncology (2024)

700 Background: Indeterminate borders of pancreatic ductal adenocarcinoma (PDAC) can impair reliability of lesion annotation in imaging assessment of therapeutic response (TR) after neoadjuvant chemotherapy (NAT). Previous work showed that longitudinal image registration algorithms can track treatment-related changes and produce quantitative imaging biomarkers (QIB) for TR that predict overall (OS) and recurrence-free survival (RFS). We compare inter-reader agreements of these biomarkers against conventional RECIST and tumor volume QIB. Methods: N=30 patients enrolled in a Phase II clinical trial comparing outcomes of a NAT regimen were retrospectively analyzed. In baseline and restaging CT, whole pancreas and tumor segmentations and tumor diameters were annotated by 2 expert attending radiologists and 2 novice radiology fellows. For each reader, percent change in tumor diameter (RECIST score), percent change in tumor volume (ΔV), and difference in ratio of tumor burden to pancreas volume (ΔB) were computed as QIB for TR across the NAT interval via two approaches: image registration of the baseline tumor region of interest, and direct segmentation of the PDAC lesion in baseline and restaging images. Inter-reader agreements of RECIST, ΔV, and ΔB QIB from both approaches were compared via concordance correlation coefficient (CCC). Associations with OS and RFS were compared over 5-year follow-up via Harrell’s C-index. Results: Among expert radiologists, RECIST score CCC was 0.77 [95% CI: 0.59-0.88], whereas image registration QIB CCC values were significantly higher (ΔV: 0.95 [0.90-0.98], p=0.002; ΔB: 0.93 [0.86-0.97], p=0.014). ΔV and ΔB QIB measured by direct tumor segmentation had significantly lower CCC than by image registration (p&lt;0.001). Among novice readers, image registration QIB (ΔV: 0.83 [0.67-0.91], ΔB: 0.70 [0.48-0.84]) produced higher agreement than RECIST (0.26 [-0.17-0.61]; p=0.002 and p=0.035), with CCC more similar to expert readers. While image registration QIB did not differ from RECIST in association with RFS, registration-based QIB predicted OS with significantly higher C-index (ΔV: 0.58 [0.56-0.60], p&lt;0.001; ΔB: 0.64 [0.62-0.66], p&lt;0.001) than RECIST (0.50 [0.45-0.55]) among experts. Conclusions: Longitudinal registration of the pancreas yields more consistent QIB for PDAC TR with stronger association to OS outcomes than RECIST. These registration-based QIB aim to advance PDAC management by improving patient-specific discrimination of TR after NAT. [Table: see text]
Efficacy and safety of fruquintinib with nab-paclitaxel in advanced G/GEJ cancer after exposure to immune checkpoint inhibitors: A single-center prospective clinical trial.
Authors: Xiaoting Ma, Kai Ou, Xiu Liu, Qi Wang, Lizhen Gao, Yongkun Sun, Lin Yang
Journal: Journal of Clinical Oncology (2024)

327 Background: Immune checkpoint inhibitors (ICIs) expanded choices of early-line therapies in advanced gastric (G)/gastro-esophageal junction (GEJ) cancer. In addition, it’s observed that early-line ICI therapy, compared to chemotherapy, could enhance the efficacy of VEGFR inhibitors with chemotherapy in late lines. This single-center prospective clinical trial was aimed to explore the efficacy and safety of fruquintinib with nab-paclitaxel as second-line in patients (pts) with G/GEJ cancer exposed to ICIs in early lines. Methods: This is a single-center, prospective, open-label clinical trial. Pts with advanced G/GEJ cancer who had been exposed to ICIs before the second line were eligible. 42 pts would receive 100g/m 2 nab-paclitaxel on day 1 and day 8 every 3 weeks, and 4mg fruquintinib from day 1 to day 14 every 3 weeks. Progression-free survival (PFS) was set as the primary endpoint. The Kaplan–Meier method would be used to evaluate time-to-event outcomes. Results: Up to Aug 10, 2023, 25 pts had been enrolled, 23 of whom were evaluable. 14 (60.9%) pts in evaluable set were male. All these pts was with stage Ⅳ of TNM staging. The median age was 58 (range: 33-74), and 6 (26.1%) pts were elder than 65 yr. 12 (63.2%) pts were with PD-L1 CPS greater than 1, 9 (47.4%) pts greater than 5, and 4 (17.4%) pts greater than 10. PD-L1 CPS of 4 pts was unknown. The pts had received a median of 5 (range: 1-20) cycles in early-line ICI therapy. 17 (73.9%) pts suffered metastasis in retroperitoneal lymph node and 7 (30.4%) pts in liver. With a median follow up time of 5.6 (range: 2.1-16.6) mo, the PFS achieved 4.8 (95% CI: 4.6-NA) mo. Despite the immatureness of overall survival (OS), the 1-year OS rate was 56.25% (95% CI: 17.27%-95.23%). The ORR was 47.8% (n=11), and DCR was 100% (n=23). As to safety, the most common (≥20%) AEs of all grades were white blood cell decrease, peripheral sensory neuropathy, and neutrophil count decrease, while that of grade≥3 was white blood cell decrease. Conclusions: Fruquintinib with nab-paclitaxel as second-line therapy demonstrated good efficacy and safety in advanced G/GEJ cancer after exposure to ICIs. ICIs might increase benefit from this therapy, which warrants further investigations in a large cohort. Clinical trial information: ChiCTR2200059976 .
Incorporating stereotactic body radiation therapy for inoperable pancreatic cancer.
Authors: Alexander Lukez, Jill S. Hasler, Sanjay S. Reddy, Efrat Dotan, Igor A. Astsaturov, Shannon M. Lynch, Kristen A. Sorice, Joshua E. Meyer
Journal: Journal of Clinical Oncology (2024)

656 Background: The management of inoperable pancreatic cancer (PC) is controversial. We sought to compare local progression (LP) for inoperable PC managed with chemotherapy (CHT) and/or stereotactic body radiation therapy (SBRT). Methods: This single-institution retrospective review analyzed 94 patients diagnosed with locally advanced (LA), medically inoperable, or metastatic PC between 2014 and 2022. Patients received CHT alone, sequential (seq) CHT + SBRT, or SBRT alone. The primary endpoints were LP and intervention due to local progression (ILP) from start of treatment. Obstructive symptoms needing intervention, percutaneous endoscopic gastrostomy tube, gastrojejunostomy, or bleeding needing transfusion were considered ILP. Primary tumor growth on imaging or ILP were defined as LP. Fine-Gray regression models with treatment received considered a time-varying covariate were used to compare ILP and LP between treatment groups where death without LP was treated as a competing risk adjusting for ECOG, stage, age and year of diagnosis. In the subgroup of patients who received SBRT, patients were stratified at the median time between diagnosis and receipt of SBRT, and risk of ILP and LP was compared between the groups using cause-specific cumulative incidence functions. Results: Of 94 patients, 51 had CHT alone, 21 received seq CHT + SBRT, and 22 had SBRT alone. The median year of diagnosis was 2019 (range, 2014 - 2022). The median ECOG was 1 with worse ECOG in SBRT alone and seq CHT + SBRT groups (p = 0.012). There were more LA or metastatic cases in the CHT (78%) and seq CHT + SBRT groups (67%) compared to the SBRT group (23%) [p &lt; 0.001]. The median SBRT dose was 36Gy (range, 25 – 40Gy) in 5 fractions. Rates of LP and ILP were higher for CHT alone (68.6%, 39.2%) compared to seq CHT + SBRT (42.9%, 38.1%) or SBRT alone (18.2%, 4.5%) [p &lt; 0.001; p = 0.004]. Higher rate of ILP associated with an increasing year of diagnosis (HR = 2.03, p &lt; 0.005) and younger age of diagnosis (HR = 0.922, p = 0.011). The median time to SBRT was 116 days. Early (&lt; 116 days) vs late SBRT LP rates differed (ILP: 4.8% vs 30%, LP: 14.3% vs 40%). Cause-specific cumulative incidence functions showed that death without LP favored early vs late SBRT (p = 0.009). Additionally, death without ILP favored early vs late SBRT (p=0.011). Conclusions: LP rates are high among patients with inoperable PC. SBRT for inoperable PC provides reasonable local control. Early SBRT reduces the need for ILP before death compared with late SBRT. Further investigation into the role of SBRT for inoperable PC is necessary. [Table: see text]
“Choosing wisely” in oncology: The example of surveillance positron emission tomography-computed tomography (PET-CT) for patients with colorectal cancer (CRC) treated with curative intent.
Authors: Roi Tschernichovsky, Talish Razi, Keren Philosoph, Idan Menashe, Ronen Arbel, Doron Netzer, Daniel A Goldstein
Journal: Journal of Clinical Oncology (2024)

216 Background: Healthcare overuse is a major challenge for healthcare systems. Professional guidelines, such as “Choosing Wisely”, have been put in place to mitigate specific areas of overuse. We examined whether the rate of unwarranted PET-CT in CRC patients treated with curative intent was successfully reduced following the adoption of “Choosing Wisely". Methods: We used the large Clalit Health Services dataset in Israel to identify patients with CRC who received adjuvant chemotherapy for localized disease between January 2017-December 2021. We then examined the number of PETCTs performed for each patient. Results: 1799 patients were included in our study (Table). We distinguished localized from metastatic cases based on specific drugs administered or not administered during the follow-up period (i.e. biologics). For the entire cohort, the median number of PETCTs performed per patient over the study period was 3. 364 (20.2%) patients underwent a single PETCT, 946 (52.6%) patients underwent ≥2 PETCTs, and 25 patients underwent ≥ 10 PETCTs. Assuming a single PETCT is considered “guideline concordant” during diagnosis and treatment of localized CRC, 52.6% (946/1799) of patients in our cohort underwent “guideline discordant” PETCT scans. Conclusions: Despite professional guidelines recommending against routine PETCT to monitor for recurrence following curative-intent treatment of CRC, there remains a large volume of “guideline-discordant” PETCTs in this space. Professional guidelines such as “Choosing Wisely” have largely failed to prevent this example of healthcare overuse. [Table: see text]