tbuckley/cabot-search huggingface dataset:
Tumor regression grade after neoadjuvant chemotherapy in patients with locally advanced gastric cancer treated with modern chemotherapy (FLOT): Experience in patients in Guatemala.
Authors: Rixci Ramirez, Daniel Estuardo Rosales-Lopez, Jennifer Dominguez, Carolina Camey, Julia Ovalle
Journal: Journal of Clinical Oncology (2024)

287 Background: Perioperative chemotherapy is the standard of care for locally advanced gastric cancers in Western populations. At this moment perioperative chemotherapy with FLOT (Fluorouracil, leucovorin, oxaliplatin and docetaxel) regimen is recommended in patients who are medically fit with benefit in progression-free survival (PFS) and overall survival (OS). However, the impact of response to this treatment is not well established. The objective of this study is to find the pathological response to FLOT chemotherapy measured by the degree of tumor regression (TRG), the benefit on disease-free survival (DFS) and OS, in patients with gastric cancer locally advanced treated with FLOT chemotherapy. Methods: Patients from the Instituto Guatemalteco de Seguridad Social (IGSS) from Guatemala City, who underwent radical gastrectomy for non-metastatic invasive gastric adenocarcinoma after perioperative chemotherapy (T1-4/N0/N+cM0) from 2019 to 2023 were included. Demographic data, clinical staging, histologic phenotype, surgical factors, tumor regression grade after gastrectomy and survival outcomes were included. The association between ORR and OS were evaluated. OS and DFS were estimated using the Kaplan Meier method with adjustment for covariates using Cox regression. Results: Thirty-eight patients with locally advanced cancer gastric were identified. The median age was 58 years (29-79), most of the patients were men (23, 61%), 35 (92%) patients have primary gastric tumor, 26 (68%) has cT3/T4 tumors and 22 (58%) has intestinal gastric cancer, all patients underwent to surgery. Two patients (6%) had TRG of 1 (complete and almost complete), 8 patients (21%) had an TGR of 2, and 28 patients (74%) had an TGR of 3; 13 patients (38%) developed recurrence, median DFS was 5.2 months (95% CI: 1.0–28). The median OS was 15.3 months (95% CI: 3.0-45). Lack of tumor regression (TRG 3) was significantly associated with lower survival HR 1.42 (1.05-2.24) p= 0.008. Clinical T4 tumors and diffuse histology were associated with poor prognostic (cT4 HR 3.04, p = 0.038, diffuse histology HR 2.08 (p = 0.001) (Table). Conclusions: Since cT4 tumors are an independent risk factor associated with poor prognostic HR 3.04, p = 0.038, it is important to make an adequate clinical staging before deciding to use three-drug treatment regimens of chemotherapy. Other factors in addition to clinical ones should be investigated, such as molecular factors that may be related to this poor response and survival in patients with cT4. This study of molecular factors is currently underway at our institution. [Table: see text]
Anlotinib plus TQB2450 as adjuvant therapy in patients with esophageal squamous cell carcinoma: A phase II study (ALTER-E005).
Authors: Changying Guo, Shengjia Chen, Yongqiang Ye, Xiao-Bing Li, Weimin Mao
Journal: Journal of Clinical Oncology (2024)

347 Background: There is currently a limited range of therapeutic options available for postoperative patients (pts) with esophageal squamous cell carcinoma (ESCC), emphasizing the urgent requirement to investigate more efficient and safer postoperative treatment regimens for resectable ESCC. TQB2450, a novel PD-L1 blockade, has shown promising activity when combined with anlotinib, an antiangiogenic agent, in the treatment of various tumors, including advanced ESCC, 1 and biliary tract cancer. 2 The ALTER-E005 study aimed to evaluate the efficacy and safety of combining anlotinib with TQB2450 as adjuvant therapy in pts with ESCC. Methods: This was a single-arm, multi-center phase II clinical trial. 30 pts (≥18 years) with histologically confirmed T1-2N1-3M0 or T3-4NanyM0 ESCC who had undergone radical (R0) resection with no recurrence 6 to 12 weeks after surgery and ECOG PS ≤ 1 would been rolled. Enrolled pts received oral anlotinib 12 mg on days 1-14 and intravenous TQB2450 1200 mg on day 1every 3 weeks for up to 16 cycles, until disease recurrence. The primary endpoint was disease recurrence free (DFS). The secondary endpoints included safety, 1-year DFS rate, 3-year DFS rate, 1-year overall survival (OS) rate, and 3-year OS rate. Results: Between August 18, 2022, and August 25, 2023, a total of 12 patients were enrolled. Out of the 12 surgically resected cases of ESCC, 11 (91.7%) had an ECOG score of 1, 10 (83.3%) were male, and 6 (50%) were under the age of 65. According to the eighth edition of the AJCC Cancer Staging Manual, 7 (58.3%) were classified as stage II, and 5 (41.7%) were classified as stage III. As of the data cut-off date (August 25, 2023), the median follow-up time was 5.1 months (95% CI: 3.4-6.8). 2 pts experienced disease recurrence, and the median duration of DFS has not yet been reached. Currently, 9 pts are still undergoing therapy, with treatment durations ranging from 0.3 months to 9.6 months. 2 pts discontinued therapy due to adverse events (AE), which subsequently improved after treatment. One patient experienced immune-related myocarditis, while the other patient had mouth ulcers and hand-foot syndrome. Additionally, one patient voluntarily withdrew from the study. Out of the total 12 patients, 3 (25%) experienced grade 3 treatment-emergent adverse events (TEAEs). There was no grade 4 or higher TEAEs reported. The grade 3 TEAEs included hand-foot syndrome (16.7%), abnormal liver function (8.3%), and immune-related hepatitis (8.3%). Conclusions: The study demonstrated the preliminary efficacy and safety of combining anlotinib with TQB2450 as adjuvant therapy in patients with ESCC who had undergone radical (R0) resection and showed no recurrence 6 to 12 weeks after surgery. 1. Zhi-Ye Zhang, et al. poster 4041: ASCO 2023. 2. Zhou J, et al. Hepatology 2022. Clinical trial information: NCT05252078 .
A retrospective analysis of the efficacy and safety of capecitabine plus oxaliplatin (CapeOX) and docetaxel plus S-1 (DS) as adjuvant chemotherapy for pathological stage III (p stage III) gastric cancer (GC).
Authors: Toru Imai, Hidekazu Hirano, Hirokazu Shoji, Toshiharu Hirose, Natsuko Tsuda Okita, Atsuo Takashima, Ken Kato
Journal: Journal of Clinical Oncology (2024)

342 Background: Adjuvant chemotherapy following surgical resection is the standard treatment for patients with p stage III GC in Japan. Although CapeOX and DS are available for adjuvant chemotherapy for stage III GC, there is limited data on which treatment is more effective. We aim to compare the efficacy and safety of CapeOX and DS as adjuvant chemotherapy in patients with p stage III GC. Methods: We extracted data of patients with p stage III GC who received either CapeOX (capecitabine on days 1–14 plus oxaliplatin on day1 for 8 cycles [q 3week]) or DS (S-1 on days 1–14 at 1 st cycle [q 3 week], docetaxel on day 1 plus S-1 on days 1–14 during 2–7 cycles [q 3 week], and S-1 on days 1–28 up to 1 year [q 6 week]) as adjuvant chemotherapy after surgical resection at our institution from February 2016 to May 2022. Three-year relapse-free survival (RFS) and adverse events (AEs) were assessed. Cox proportional hazard model was used in multivariable analysis to assess the effect of independent variables on RFS. Results: A total of 74 patients were included in this study (CapeOX 31/ DS 43). Patient characteristics (CapeOX/DS) were as follows: median age, 60/64 years; male, 77/65 %; ECOG-PS 0/1, 45%/44%, 55%/56 %; p stage IIIA/IIIB/IIIC, 10%/30%, 48%/51 %, 42%/19 %. The 3-year RFS was 37% in the (hazard ratio [HR] = 0.81, P=0.48). For p stage IIIA, IIIB, and IIIC, the 3-year RFS in the CapeOX group and the DS group was 67% vs. 75% (HR = 0.56, P =0.52), 43% vs. 42% (HR = 1.11, P =0.81), and 23% vs. 0% (HR = 1.59, P =0.39), respectively. Multivariable analysis adjusted for p stage showed no significant differences in RFS between the CapeOX group and the DS group (HR=1.06, P=0.85). Compared to DS, CapeOX was associated with lower incidences of febrile neutropenia (0% vs 7%) and alopecia (6% vs 74%), and a higher incidence of peripheral neuropathy (80% vs 23%). Conclusions: This analysis indicates that CapeOX and DS have comparable efficacy as adjuvant chemotherapy for p stage III GC in terms of RFS, albeit with different profiles of AEs.
Treatment development targeting Hippo pathway for scirrhous type gastric cancer.
Authors: Yuichiro Miki, Mami Yoshii, Kenji Kuroda, Hironari Miyamoto, Tatsuro Tamura, Takahiro Toyokawa, Shigeru Lee, Kiyoshi Maeda
Journal: Journal of Clinical Oncology (2024)

398 Background: Treatment outcome of gastric cancer (GC) has been improved by minimally invasive surgery, and development of new drugs including immune checkpoint inhibitors. However, survival for patients with scirrhous type (SGC, Type4) gastric cancer is dismal. Methods: We collected miRNAs form exosomes released from cancer associated fibroblasts which is developed from resected gastric cancer tissue. Pathway enrichment analysis (PEA) of top miRNAs showed that they are significantly associated with Hippo signaling pathway (Hippo pathway). The molecules relating Hippo pathway was evaluated by Western blotting in cell line, and IHC of tissue array. Results: PEA using top miRNAs showed the significant relationship to Hippo pathway. Yap is a final effector in this pathway, and we found that YAP is not expressed in MKN45 cells (diffuse type), which is supposed to be degraded in cytoplasm. On the contrary, MKN74 cells express both YAP and pYAP. IHC showed that YAP translocation to nucleus is significantly associated with CTGF expression. CTGF low expression is significantly associated with worse prognosis especially in diffuse type GC (Log rank p = 0.022). This trend is similar in the analysis of patients with SGC. Conclusions: The role of Hippo pathway is different between intestinal type and diffuse type of GC. YAP activator could be effective for the treatment of SGC, and we are focusing on the treatment development.
Real-world biomarker testing patterns among patients with metastatic colorectal cancer (mCRC) treated with later lines of therapy (LOT) in the United States (US) community oncology setting.
Authors: Arvind Katta, Afsaneh Barzi, Brian Thomas Hocum, Sreevalsa Appukkutan, David Cosgrove, Ila Sruti, Junxin Shi, Wei Dai, Gregory A. Patton, Svetlana Babajanyan, Tanios S. Bekaii-Saab
Journal: Journal of Clinical Oncology (2024)

163 Background: Testing for BRAF and KRAS/NRAS mutations, HER2 amplifications, and MSI/MMR status is a standard of care for all patients with mCRC. There are limited real-world (RW) data regarding biomarker testing patterns among robust patients who are candidates for multiple LOT. We evaluated biomarker testing patterns among patients treated in community oncology practices who initiated regorafenib (REGO) and/or trifluridine/tipiracil (FTD/TPI), predominantly in 3 rd or later lines of therapy. Methods: A retrospective analysis utilizing electronic medical record data from The US Oncology Network examined adult patients with mCRC who initiated REGO and/or FTD/TPI between 09/01/2015 and 11/30/2022 with follow-up until 05/31/2023. The proportion of patients tested for various biomarkers was assessed. Results: A total of 2684 mCRC patients initiated REGO and/or FTD/TPI (including 895 pts receiving both) in any LOT during the study period. The mean age of patients at baseline was 62.9 years, of whom 54.9% were male, 1599 (59.6%) patients were White and 436 (16.2%) were underrepresented minorities (Black or Hispanic/Latino). Patients were most commonly tested for KRAS mutations (75.2%) and least commonly for HER2 amplifications (22.6%). Age, gender, and race/ethnicity characteristics were similar between treatment subgroups, with 29.6% of minority and 23.1% of white patients not undergoing KRAS testing. Types of biomarkers tested and proportion of patients tested are reported in the table below. Conclusions: About one quarter of patients who were sufficiently robust to receive aggressive therapy did not undergo testing for KRAS, the oldest standard of care biomarker in CRC. We observed disparities by race/ethnicity. We also observed a correlation between rates of testing and treatment intensity, with patients who received both REGO and FTD/TPI having a higher rate of testing than those who received only one of the treatments. Understanding the pitfalls in biomarker testing will help pave the way for appropriate and equitable access to cancer care. [Table: see text]
Prognostic factors of patients (pts) with salvage-line metastatic colorectal cancer (mCRC).
Authors: Hideaki Bando, Eiji Oki, Yuriko Takeda, Toshihiro Misumi, Motoko Suzuki, Masashi Wakabayashi, Kentaro Yamazaki, Axel Grothey, Robert J. Mayer, Jin Li, Thierry Andre, Qian Shi, Aimery De Gramont, Takayuki Yoshino
Journal: Journal of Clinical Oncology (2024)

115 Background: Randomized clinical trials provide the best evidence for the effects of a new treatment. However, the use of a placebo control arm may present practical and ethical concerns for enrolled patients and treating providers. The CRC ARCAD global database includes a total of 1,673 individual patient data (IPD) treated with placebo plus best supportive care in a salvage-line setting for refractory mCRC. By using placebo IPD, we have proposed to construct a synthetic control arm for clinical trials (Yoshino T. et al., Nature Medicine 2023). Methods: From 40,889 IPD from 59 studies in ARCAD mCRC database, 723 placebo pts were selected from 4 placebo-controlled randomized studies in a salvage-line setting (CORRECT, RECOURSE, CONCUR and TERRA). We analyzed the impact of baseline patient characteristics and various prognostic factors on outcome in the placebo control. Results: The adjusted hazard ratios (HRs) (95% confidence interval [CI]) were 0.52 (0.40-0.67) for the number of metastatic sites (1 vs 2+), 0.71 (0.59-0.84) for ECOG performance status (PS) (0 vs 1), 0.54 (0.45-0.66) for liver metastases (No vs Yes), 0.54 (0.40-0.71) for peritoneal metastases (No vs Yes), and 0.51 (0.38-0.70) for Royal Marsden Hospital (RMH) Score (consisting of albumin level, number of metastatic sites, and LDH level) (0-1 vs 2-3). Conclusions: Number of metastatic sites, ECOG PS, liver metastasis, peritoneal metastasis and RMH Score were significant prognostic factors in patients with mCRC receiving placebo in a salvage-line setting. Further prognostic factors should be investigated to increase the accuracy of the proposed synthetic control arm. [Table: see text]
Metachronous remnant gastric cancer after proximal gastrectomy.
Authors: Kenichi Ishizu, Takaki Yoshikawa, Rei Ogawa, Masahi Nishino, Ryota Sakon, Takeyuki Wada, Tsutomu Hayashi, Yukinori Yamagata
Journal: Journal of Clinical Oncology (2024)

260 Background: Proximal gastrectomy is frequently selected for early gastric cancer located at the upper third of the stomach. Annual postoperative endoscopy is considered to be useful for the early detection of metachronous remnant gastric cancer (MRGC). Despite that, we sometimes have also encountered cases that are not suitable for endoscopic resection (ER). The aim of this study is to identify the risk factors for the patients who developed MRGC after proximal gastrectomy, received annual endoscopy, but are not eligible for ER (non-ER). Methods: We retrospectively analyzed 191 patients who had received annual endoscopic surveillance after undergoing PG for cT1 gastric cancer at NCCH between 2006-2015. MRGCs were categorized into two groups: ER group and non-ER group. The remnant stomach was defined as three locations: pseudo-fornix (PF), corpus and antrum. Results: The median observation period was 73 (range 12-168) months. MRGC was observed in 29 cases with 32 lesions. ER was eligible for 20 lesions (ER group, 62.5%), but 12 were not (non-ER group, 37.5%). We compared the characteristics between of ER group and non-ER group in terms of sex, age (&gt;65 years), interval from the initial surgery (&gt;60months), the location (PF vs non-PF), and cross-sectional circumference (posterior wall vs. others). In both univariate and multivariate logistic regression analysis, only the location at PF was identified as a risk factor for non-ER group (OR 25.0, 95% CI: 1.8–339, p = 0.015). Among 12 lesions of the non-ER group, the location of PF was found in 6 (50%) lesions. As compared with MRGC at the non-PF, that at the PF (n = 6) was characterized by younger patients (57.5 (range 37-69) years vs. 69 (56-77) years), larger size (36 (7-57) mm vs. 9 (9-24) mm), deeper depth (MP or deeper; 5/6 vs. 0/6), more frequent undifferentiated-type histology (4/6 vs. 0/6) and frequent nodal metastasis (3/6 vs. 0/6). The interval to detect MRGC appears to be longer in the PF (78 (31-96) months than that of the non-PF (60 (31-96) months), but the difference was not statistically significant (p = 0.86). Then, we examined the visibility and the mucosal normality of the area developing MRGC in the annual follow-up endoscopy one year before the detection of MRGC (n =32). In 25 lesions at the non-PF, the visibility and the mucosal normality was secured in 21 (84%). while 5 PF lesions were difficult to observe (71.4%, p = 0.01) due to food residues in 4 (57%, p = 0.047) and insufficient expansion of the gastric mucosa in 4 (57%, p = 0.001). Conclusions: Detection of the MRGC at the PF at an early stage is crucial and challenging. With annual follow-up endoscopy, complete clearance and adequately extending the gastric mucosa could lead to the early detection of MRGC at the PF.
Short-term and long-term results of robot-assisted esophagectomy in cT3br/T4b esophageal cancer at initial diagnosis: Comparison with conventional thoracoscopic surgery.
Authors: Takeo Fujita, Kazuma Sato, Naoto Fujiwara, Hiroyuki Daiko
Journal: Journal of Clinical Oncology (2024)

284 Background: Conversion surgery in patients with locally advanced esophageal cancer that is not resectable at first time and has responded to prior therapy remains unclear. Recently, the usefulness of RAMIE for locally advanced esophageal cancer has begun to be discussed. In this study, we first analyzed the short- and long-term results of RAMIE, then examined the results of conversion RAMIE in T3br/T4b patients, and compared them with those of conversion using conventional MIE. Methods: Short-term and long-term postoperative outcomes were analyzed in 203 cases of robot-assisted esophageal cancer resection between 2020/1 and 2023/08. In addition, 33 patients with T3br/T4b who were initially diagnosed with cT3br/T4b and who underwent RAMIE after prior treatment were selected and compared to 48 cT3br/T4b cases with conventional MIE performed at the same time. Results: The mean age of RAMIE patients was 66.2 years, male to female ratio 170:33, preoperative treatment including NAC 150:53, and Clinical Stage I:II:III:IV 41:27:97:38. Surgical outcomes included thoracic surgery time of 200.3 min and total blood loss of 154.4 ml. Perioperative outcomes were Clavien-Dindo Grade 1 or higher: suture failure 4.4%, pneumonia 13.3%, and recurrent nerve palsy 16.7%. Long-term prognostic analysis (MST: 483.6days) showed 3yOS:97.6/94.1/80.3/70.9% and 3yDFS:96.2/87.2/66.2/52.4% in cStage I/II/III/IV. Especially in cStage II/III patients, 3yOS: 81.5%, 3yDFS: 71.4%. Long-term outcomes were not significantly different from those of conventional thoracoscopic procedures performed at the same time. Perioperative outcomes in cT3br/cT4b patients at initial presentation were pneumonia: 18.1%, recurrent nerve palsy rate: 12.1% (excluding complicated resection cases), and these 3yOS:66.2% and 3yDFS:48.7%. The 3yOS:52.7% and 3yDFS:40.3% of cT3br/T4b cases in the usual MIE showed a favorable trend in RAMIE (p=002). Of the 38 patients with recurrence after RAMIE surgery, 19 were local/regional and 19 were distant. Of these, 5/6/5/3 were brain/lung/liver/LN+others as the first site of distant metastasis. Conclusions: The short- and long-term results of RAMIE in our department, including T3br/T4, were described, and the short-term and long-term results of RAMIE were considered acceptable. In terms of recurrence, local/regional disease control was considered to be relatively good.
Preclinical analysis and clinical validation to identify biomarkers of regorafenib efficacy in patients with metastatic colorectal cancer.
Authors: Mitsukuni Suenaga, Tetsuo Mashima, Naomi Kawata, Shingo Dan, Hiroyuki Seimiya, Kensei Yamaguchi
Journal: Journal of Clinical Oncology (2024)

171 Background: In the identification of biomarkers for anticancer drugs, the lack of objectivity in the selection of candidate factors makes it difficult to interpret the mechanism. We performed preclinical analysis and translational validation study to identify the candidate cytokines for regorafenib efficacy in metastatic colorectal cancer (mCRC) patients. Methods: As a first preclinical process, we selected candidate cytokines according to our gene chip analysis using a panel of human cancer cell lines (JFCR39). We then validated predictive value of the cytokines in mCRC patients receiving regorafenib (discovery, N=54) and FTD/TPI (control, N=16). Blood samples were obtained at baseline (BL), before second cycle (2nd) and progressive disease (PD), and cytokine levels were measured using ELISA. Finally, we measured changes in cytokine levels and cell number in colorectal cancer cell lines treated with regorafenib. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier curves. Results: Our gene chip analysis showed association between high matrix metalloproteinase (MMP)-14 expression and high sensitivity to regorafenib, and the MMPs pathway was examined in blood samples. In the discovery cohort, high MMP14 levels at BL (mean 2.66 vs. 1.91 ng/ml, P=0.006) and PD (mean 2.34 vs. 1.71 ng/ml, P=0.02) were associated with tumor shrinkage, and high MMP14 levels at PD were associated with longer PFS (3.7 vs. 2.5 mos, HR0.45, 95%CI: 0.21-0.95, P=0.03). Patients with decreased MMP9 levels at 2nd had higher disease control rate (74% vs. 29%, P=0.002) and tumor shrinkage (52% vs. 13%, P=0.006), longer PFS (4.5 vs. 2.0 mos, HR0.34, 95%CI: 0.18-0.65, P&lt;0.001) and OS (13.6 vs. 5.2 mos, HR0.35, 95%CI:0.18-0.68, P=0.001) than those with increased changes. These findings were not observed in the control cohort, but MMP9 levels decreased at 2nd in 93.8% of patients. In a regorafenib-sensitive cell line, HT29, MMP14 levels were increased whereas there was no change in regorafenib-resistant HCT15 cells. Conclusions: Our preclinical data-based translational validation study suggests that MMP14 and MMP9 may serve as a prognostic marker of regorafenib, and the results also provide insight for novel combination therapy with anti-MMP9 agent or FTD/TPI.