tbuckley/cabot-search huggingface dataset:
Association of FGFR2 structural alterations in intrahepatic cholangiocarcinomas with female gender and younger age.
Authors: Zishuo Ian Hu, Jeffrey S. Ross, Dean C. Pavlick, David Hsieh
Journal: Journal of Clinical Oncology (2024)

537 Background: FGFR2 fusions and other rearrangements are targetable alterations due to the advent of FGFR2 kinase domain inhibitors, and are considerably more common in intrahepatic cholangiocarcinomas (iCCA) than other cancer types. Understanding clinical factors associated with FGFR2 fusions and other rearrangements may guide precision oncology efforts. Prior studies indicate that FGFR2 alterations are more common in younger patients, but it remains unknown whether other demographics are specifically associated with FGFR2 structural alterations. Here, we reviewed the frequency of FGFR2 structural alterations in 8,898 iCCA patients from the AACR Genie and the Foundation Medicine databases. Methods: We reviewed the Foundation Medicine (n= 7,934) and AACR GENIE database (n=964) for intrahepatic cholangiocarcinomas. We identified iCCAs with FGFR2 structural alterations and mutations in other common driver genes and analyzed their distribution by age and sex. Results: FGFR2 structural alterations were more frequent in female (10.4%) compared to male (6.4%) patients across both cohorts. FGFR2 structural alterations had an association with an odds ratio of 2.5 (95% CI 1.6-3.7) and 1.7 (95% CI-2.0) with the female gender in the AACR GENIE and Foundation Medicine databases, respectively. The frequency of FGFR2 fusions/rearrangement was highest during reproductive years (up to age 40) and subsequently declined with age. This decline was greater in females than males. Mutations in other genes associated with iCCA including non-fusion FGFR2 alterations, and mutations in ARID1A, KRAS, and TP53 were not associated with gender or age. Conclusions: Our results show that FGFR2 structural alterations are significantly enriched in younger female patients with iCCA. Clinical assessment of FGFR2 alterations should be prioritized in this patient population, and future clinical studies in this molecular subtype should ensure inclusive enrollment practices. Further research is warranted to determine if the pathogenesis of FGFR2 structural alterations are driven by female biology including the involvement of sex hormones and the potential impact on the development of acquired resistance to FGFR2 kinase inhibitors.
Clinicopathological features of post-colonoscopy colorectal cancer in patients with Japanese Lynch syndrome: A multicentric retrospective observational study.
Authors: Akinari Takao, Toshiro Iizuka, Misato Takao, Akiko Chino, Kiwamu Akagi, Masayoshi Yamada, Kohji Tanakaya, Hideyuki Ishida, Koji Komori, Kazuhito Sasaki, Masashi Miguchi, Keiji Hirata, Tomoya Sudo, Yasuyuki Miyakura, Toshiaki Ishikawa, Tatsuro Yamaguchi, Naohiro Tomita, Yoichi Ajioka
Journal: Journal of Clinical Oncology (2024)

79 Background: Due to the high incidence of heterochronic and concurrent colorectal cancer in Lynch syndrome (LS), colonoscopic surveillance is recommended in Japan every 1-2 years. Even with regular colonoscopic surveillance, post-colonoscopy colorectal cancer (PCCRC) often occurs in the intervals between surveillance, but there are currently no reports of the details of PCCRC in LS in Japan. Methods: Of 1756 colonoscopies performed between 2009 and 2018 in 316 patients with a diagnosis of LS confirmed by genetic testing who were enrolled in a nationwide, Japanese, multicentric study conducted by the Committee of Hereditary Colorectal Cancer of the Japanese Society for Cancer and Rectum, 1203 colonoscopies in 256 patients were assessed to determine the clinicopathological characteristics of PCCRC, after including cases of first-time surveillance, previously untreated lesions, and inadequate pretreatment. Then, the incidence of PCCRC was compared between patients with a median surveillance colonoscopy interval &lt; 12 months (group A) and &gt; 12 months (group B). Results: There were 49 cases of PCCRC with a total of 84 lesions. The number of lesions per tumor depth was 66, one, five, seven, four, and one for pTis, pT1, pT1a, pT1b, pT2, and pT3, respectively. Two (2.4%), 20 (23.8%), 21 (25%), four (4.8%), 18 (21.4%), and 19 (22.6%) lesions were localized in the cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum, respectively. In pTis-pT1b, the macroscopic type was 0-IIa in 33 lesions (41.8%), 0-IIc in four lesions (5.1%), 0-IIa+IIc in five lesions (6.3%), 0-IIb in one lesion (1.3%), 0-Is in 15 lesions (19%), 0-Ip in one lesion (1.3%), 0-Isp in 16 lesions (20.3%), and unknown in four lesions. In pT1b-pT3, seven lesions (63.6%) were smaller than 20 mm. In terms of the median interval between surveillance colonoscopies, 130 patients had a median interval &lt; 12 months (group A), and 126 patients had a median interval &gt; 12 months (group B). In groups A and B, PCCRC, metachronous cases, simultaneous cases, and depths than pT1b were observed in 29 (22%) and 20 (16%) cases (p=0.21); 14 (11%) and two (1.6%) cases (p=0.006); six (4.6%) and one (0.8%) case (p=0.22), and six (4.6%) and four (3.2%) cases (p=1), respectively. Conclusions: In PCCRC in Lynch syndrome, invasive carcinomas &lt; 2 cm should be noted. In addition, a surveillance interval of 12 months may be insufficient in patients with LS. Thus, further investigation is warranted.
A two-arm randomized open-label prospective design superiority phase III clinical trial to compare the efficacy of docetaxel-oxaliplatin-capecitabine/5 fluorouracil (DOC/F) followed by docetaxel versus CAPOX/mFOLFOX-7 in advanced gastric cancers (DOC-GC study).
Authors: Anant Ramaswamy, Prabhat Ghanshyam Bhargava, Biswajit Dubashi, Akhil Kapoor, Sujay Srinivas, Omshree Shetty, Rajiv Kumar Kaushal, Aekta Shah, Vanita Noronha, Amit Joshi, Nandini Sharrel Menon, Chaitali Nashikkar, Anuj Gupta, Bal Krishna Mishra, Smita Kayal, Ramesh Ananthakrishnan, Suman Kumar, Prasanth Ganesan, Kumar Prabhash, Vikas S. Ostwal
Journal: Journal of Clinical Oncology (2024)

LBA248 Background: The choice of optimal chemotherapy in advanced (unresectable/metastatic) gastroesophageal junction and gastric (GEJ/G) adenocarcinomas remains undecided with regard to the addition of docetaxel to a FOLFOX/CAPOX backbone in improving outcomes with equipoise with regard to the optimal duration of chemotherapy as well. Methods: The DOC GC study is a multicentric open-label, randomized controlled phase III trial, in adults ≥18 years with advanced GEJ/G adenocarcinoma and adequate end-organ function. Patients were randomized 1:1 to one of two arms: Arm A - modified CAPOX (3 weekly) or modified FOLFOX-7 (2 weekly) for a maximum of 6 months and then observation OR Arm B: modified FLOT (5-FU/leucovorin /Oxaliplatin/Docetaxel) or DOX (docetaxel/oxaliplatin/capecitabine) every 2 weeks for a maximum of four months followed by Docetaxel (60mg/m2) every 3 weeks till disease progression, unacceptable toxicity, or patient's decision to withdraw. The primary endpoint of the study is Overall survival (OS), as calculated by Kaplan-Meier method, while key secondary endpoints include Progression-free survival, and adverse event rates. Results: Of the 324 patients randomized between July 2020 and November 2022, 305 patients were evaluable for analysis (Arm A: 156; Arm B: 149). With a median follow-up time of 19.2 months (95% CI: 16.5 – 21.9) for the entire cohort, the median OS was 10.1 months (95%: 9.2-10.9) in Arm A and 8.9 months (95% CI: 7.3-10.5) in arm B and this difference was not statistically significant [p=0.70]. There were no statistical differences in median PFS between the two arms [Arm A: 7.1 months (95% CI: 6.1-8.1); Arm B: 6.2 months (95% CI: 5.7 – 6.8); p=0.39]. An increased proportion of grade 3/4 neutropenia (21% vs. 5.1%; p&lt;0.001) was seen in patients in Arm B, with other treatment related side effects being comparable between the two arms. A greater proportion of patients in Arm A tended to receive second line therapy compared to Arm B (38% vs. 26%; p=0.07). Conclusions: The addition of docetaxel to a doublet regimen comprising 5-fluorouracil/capecitabine and oxaliplatin did not improve overall survival in patients with advanced GEJ/G cancers. Continuing chemotherapy beyond six months also does not appear to improve survival in this group of cancers. Clinical trial information: CTRI/2020/03/023944 .
FLOT compared to FOLFOX/XELOX as a neoadjuvant chemotherapy in locally advanced gastric cancer: Experience of two clinics.
Authors: Nikolay Semenov, Kamil Dalgatov, Roman Izrailov, Lyudmila Zhukova
Journal: Journal of Clinical Oncology (2024)

361 Background: The optimal regimen of neoadjuvant chemotherapy (NCT) in locally advanced gastric cancer (GC) remains controversial, especially whether triplet (FLOT) or duplet (FOLFOX/XELOX) regimen is superior since escalation does not always lead to significant clinical improvement. The aim of this study is to assess efficacy of triplet and duplet chemotherapy regimens as a neoadjuvant approach in locally advanced GC via retrospective data. Methods: We queried the data for 334 patients with locally advanced GC (cT2-4 or cN+) diagnosed in 2016–2023 yy administered with multi-agent NCT: FLOT or XELOX/FOLFOX. The primary endpoints were the ratio of patients with disease progression on NCT, rates of ypN0, and rates of pathological complete response (pCR). Secondary endpoints included progression free survival (PFS) and overall survival (OS). Results: 156 patients (out of total 334 included in the study) received doublet NCT (FOLFOX/XELOX, 8/6 cycles respectively), 61.5% were males, median age was 67.4 (range 21.3-85.4) years, 88.2% had cT3-4. and 22.4% had locally advanced gastroesophageal junction (GEJ) adenocarcinoma. 177 patients were treated with triple NCT (FLOT, 8 cycles), 62.1% were males, median age was 59.9 years, 89.2% had cT3-4, and locally advanced GEJ adenocarcinoma was diagnosed in 21.0%. At a median follow up of 34.7 months (mth) using FLOT regimen as NCT was associated with better clinical outcomes. The ratio of patients who have progressed on NCT was 21.5% and 31% in triplet and doublet arms, respectively (p=0.098). Rates of ypN0 were 50.5% in FLOT arm and 43.7% in XELOX/FOLFOX arm (p=0.36). pCR was achieved in 8.2% and 6.3% in FLOT and XELOX/FOLFOX arms, respectively (p=0.59). Median PFS was 20.3 mth in FLOT arm in comparison to 15.7 mth in FOLFOX/XELOX arm (p=0.012). Median OS was not reached (NR) for triplet arm and was 25.1 mth for doublet arm (p= 0.003). Patients who conversed resectable disease had median PFS of 34.5 and 23.1 months for FLOT and FOLFOX/XELOX arms, respectively (p=0.024). Median OS in these subgroups was NR and 37.0 mth (p=0.003). Conclusions: We report that triplet regimen (FLOT) in comparison with doublet (FOLFOX/XELOX) regimen is the more favorable option as a neoadjuvant setting in locally advanced gastric cancer. FLOT NCT is associated with increased ypN0, pCR and shows statistically significant difference in PFS and OS.
Preoperative weight loss program for hepatocellular carcinoma patients with high body mass index in hepatectomy.
Authors: Yu Saito, Yuji Morine, Shinichiro Yamada, Hiroki Teraoku, Tetsuya Ikemoto, Mitsuo Shimada
Journal: Journal of Clinical Oncology (2024)

565 Background: This study aimed to investigate the usefulness of a weight-loss program (WLP) in patients with a high body mass index (BMI) prior to liver resection (Hx) for hepatocellular carcinoma (HCC). Methods: Among 445 patients with HCC who underwent initial Hx between 2000 and 2020, 19 with a high BMI (≥25.0) were enrolled in our WLP since 2014. For calorie restriction, the amount of energy consumed was calculated as the standard body weight (SBW) kg × 20–25 kcal/day. Protein mass was calculated as SBW kg × 1.0–1.2 g/day to maintain skeletal muscle mass. Patients also performed both aerobic and resistance exercises. The before-and-after changes were compared, and the effect of WLP on the short- and long-term results was investigated. Results: The average length of WLP was 21 days, and weight loss was successfully achieved in all patients. Body fat mass was reduced during the program, while skeletal muscle mass was maintained. WLP led to improvements in liver function and fibrotic markers, without tumor progression. There were no postoperative complications (≥Clavien–Dindo [CD] III). A retrospective comparison of postoperative outcomes revealed that those in the WLP group showed a significantly shorter operation time and improved postoperative morbidity rate (≥CD III) with decreased postoperative hospital stay. There were no significant differences in long-term prognosis based on participation in the WLP. Conclusions: WLP with multidisciplinary intervention improved short-term outcomes after Hx in patients with HCC and a high BMI.
Hepatic arterial infusion pump chemotherapy in patients with advanced intrahepatic cholangiocarcinoma confined to the liver: A multicenter phase II trial.
Authors: Stijn Franssen, Merve Rousian, Lynn E. Nooijen, Britte H.E.A. ten Haaft, Michael Doukas, Nadia Haj Mohammad, Heinz-Josef Klümpen, Adriaan Moelker, Bianca Mostert, Jeroen Hagendoorn, Rutger-Jan Swijnenburg, Marjolein Y.V. Homs, Bas Groot Koerkamp
Journal: Journal of Clinical Oncology (2024)

433 Background: In the ABC-trials, the 3-year overall survival (OS) was only 2.8% for patients with advanced intrahepatic cholangiocarcinoma (iCCA) confined to the liver who received systemic gemcitabine with cisplatin. Hepatic arterial infusion pump (HAIP) combined with systemic chemotherapy had a pooled 3-year OS of 39.5% in a recent meta-analysis. HAIP chemotherapy involves continuous administration of floxuridine (FUDR) directly into the hepatic artery using a subcutaneous pump. The aim of this study was to prospectively assess the effectiveness of HAIP with systemic chemotherapy in patients with advanced iCCA confined to the liver in the Netherlands. Methods: We performed a single arm phase II trial in 3 centers in the Netherlands. Six cycles of HAIP chemotherapy with floxuridine were scheduled with 8 cycles of concurrent systemic chemotherapy with gemcitabine and cisplatin, if not administered previously. The primary endpoint was OS, secondary endpoints were progression-free survival (PFS) and objective response. Results: From January 2020 until September 2022, 50 patients with advanced iCCA were included. Combined HAIP and systemic chemotherapy was administered to 38 patients (76.0%). Eleven patients (22.0%) received HAIP chemotherapy alone, because they had received systemic treatment before enrollment. One patient (2.0%) didn’t start treatment, because he died 19 days after pump implantation due to COVID-19. The median follow-up was 26.4 months (95% CI: 21.7 – 39.0). The median OS was 22.1 months (95% CI: 19.7 – not reached). The 1-year OS rate was 80.0% (95% CI: 69.6% – 91.9%); the 3-year OS rate was 28.6% (95% CI: 16.0% – 51.2%). The median PFS was 10.0 months (95% CI: 8.7 – 12.2). An objective response on imaging (RECIST) was achieved in 27 patients (54.0%) and disease control at 6 months in 43 patients (86.0%). Four patients (8.0%) underwent a resection after HAIP chemotherapy of whom 2 patients had a complete pathologic response. Conclusions: Combined HAIP with systemic chemotherapy for patients with advanced iCCA was associated with a favorable 3-year OS of 28.6% compared with 2.8% after systemic chemotherapy alone in the ABC trials. Clinical trial information: NL8234 .
Investigating the association of WNT pathway dysregulation and young-onset colorectal cancer.
Authors: Morgan Ferrell, Deniz Can Guven, Cyndi Gonzalez, Richard Giza, Svea Cheng, Masood Pasha Syed, Tara Magge, Aatur D. Singhi, Anwaar Saeed, Ibrahim Halil Sahin
Journal: Journal of Clinical Oncology (2024)

217 Background: Colorectal cancer (CRC) is the third most common cancer in the United States with studies showing increasing incidence of Young-Onset CRC, defined as cases occurring in individuals 50 years old or younger. Separately, the WNT Signaling Pathway and its subsequent mutation can result in sustained activation and, therefore, unregulated cell proliferation which has been well described in colorectal cancers. Loss of function in APC, AXIN1, AXIN2, GKS3B, and RNF43 can each act to dysregulate WNT signaling, contributing to cancer development. In this study, we aimed to conduct a comprehensive, molecular evaluation of the WNT signaling pathway in colorectal cancer within age-specific cohorts with onset of CRC at 50 years old or less versus greater than 50 years old. Methods: We used published individual patient-level data of 6286 patients with colorectal cancer (CRC) from the 16 CRC datasets included in the cbioportal database. The WNT pathway alterations, including APC, AXIN1, AXIN2, GKS3B and RNF43 mutations were considered to define the WNT mutant CRC cohort. The presence of WNT alterations according to the age (50 years old or younger vs. over 50 years) were evaluated using Chi-square tests. The association between primary tumor distribution (colon vs. rectal) and age were evaluated across patients with and without WNT pathway alterations. The effect of WNT pathway alterations on the overall survival and survival after the metastatic stage was evaluated with Kaplan-Meier survival curves. A type-I error level of 5% (p&lt;0.05) was considered the threshold limit for statistical significance. Results: A total of 2,630 individuals were identified with relevant clinical and molecular information. When comparing WNT alteration patterns between young-onset CRC (&lt; 50 years old) and CRC in cohort &gt;50 years old, there was no statistically significant difference (p-value .215). Analysis of common individual mutations in APC, AXIN1, AXIN2, GKS3B and RNF43 also showed similar incidences across age groups. However, we identified WNT alterations were significantly more common in rectal cancers compared to colon cancer, being found in 75.9% of rectal cancer cases, regardless of age groups (p-value &lt;0.00001). Additionally, individuals identified to have WNT alterations were found to have improved survival with a median overall survival of of 58.19 months versus a median of 41.72 months in those without. Conclusions: Overall, no significant differences were found in WNT alteration expression between Young-onset CRC versus CRC in individuals over the age of 50. However, across all age groups, WNT alterations were frequently found in rectal cancers. Furthermore, these WNT alterations were associated with better outcomes.
Association of <i>KRAS</i> G12C status with age at onset of metastatic colorectal cancer in the Brazilian population: A multicenter analysis of a molecular profile database (RAS, BRAF and MSI status).
Authors: Marcelo Aruquipa, Renata D'Alpino Peixoto, Rodrigo Dienstmann, Fernanda Oliveira, Vinicius Lorandi
Journal: Journal of Clinical Oncology (2024)

173 Background: Precision oncology has changed clinical practice in metastatic colorectal cancer (mCRC). However, there is little data about molecular epidemiology of mCRC in Brazil. Our study aims to create a nation-wide database to develop future projects in the Oncoclinicas Group. Methods: This was an observational, retrospective, and multicenter study. Anonymized medical records of adult patients (18 years or older) with mCRC from January 2019 to July 2023 were reviewed. All specimens were centrally reviewed in our laboratory (all tissue-based analysis). Demographic data included age, gender, region of origin and sidedness. Molecular data included RAS, BRAF and MMR status. Descriptive statistics, frequencies and percentages were used for categorical variables, while mean and medians for numerical variables. The correlation between variables was analyzed through Chi-square and T-test (when applicable). Significance for all results was established as a p value of &lt; 0.05. The statistical software used was SPSS. Results: A total of 858 cases were included. Median age was 63.7 y/o (range 22-95) and 11.9% were &lt; 45 y/o. Male patients represented 50.3% of the population and 76.1% were from the Southeast region. Left-sided tumors comprised 59.2% of the cases, 36.8% were right-sided and 4% were not specified. Wild-type KRAS corresponded to 46.7% of the total cases, while 49.4% were KRAS mutant and 3.9% NRAS mutant. The most common KRAS mutations were G12V (27.6%) and G12D (23.5%). KRAS G12C mutation was found in 6.4% of all KRAS mutant tumors. The most common NRAS mutation was the Q61K (24.2%). Only 7.3% of cases were BRAF mutated, most of them V600E, only 5 non-V600E mutations were detected. MSI-high was present in 14 cases only (1.6%). In the age-stratified analysis, left-sidedness (p=0.001) and KRAS G12C mutation (p=0.016) were associated with younger age (&lt;45 y/o). In the sidedness-stratified analysis, younger age (p=0.001), BRAF mutation (p=0.001) and MSI-high status (p=0.009), were more common in right-sided tumors. Conclusions: In our Brazilian cohort of mCRC patients, frequencies of RAS and BRAF mutations were similar to worldwide data. However, we found lower than expected frequency of MSI-high tumors. KRAS G12C mutation was associated with early-onset mCRC, an emergent population in which KRAS G12C inhibitors might be particulary useful. To the best of our knowledge, this is the largest cohort in the Brazilian population with mCRC reporting RAS, BRAF and MSI status. Larger studies are needed to confirm these findings.