bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation of 3 month therapy for stage III colon cancer in a large community practice.
Authors: Shklar Victoria , Barnes Martin Christopher , Chaudhary Hira , Ukrani Janta , Staszewski Harry 
Published: June 2023

e15653 Background: Standard adjuvant chemotherapy for Stage III colon cancer comprises FOLFOX (5 FU/oxaliplatin(OX)/leucovorin) or CAPOX (capecitabine (CAP), OX) for six months. Toxicity from OX impacts quality of life and persists beyond treatment. In March 2018, the NEJM published the IDEA study demonstrating that 3 month FOLFOX or CAPOX was non-inferior to 6 month with less toxicity, specifically in low risk (LR) populations ( < T4 and/or < N2). National guidelines then incorporated 3 month options. We profiled adoption of these regimens at NY Cancer & Blood Specialists after updated guidelines were published. By examining guideline compliance we hope to improve the treatment of patients with Stage III. Methods: We retrospectively reviewed all 234 electronic charts of patients presenting for management of Stage III after the NEJM publication. Substage, duration of therapy, and reasons for delay or discontinuation were analyzed. Results: 234 patients underwent surgery and presented for consideration of adjuvant therapy. 32 (14%) had stage IIIA, 164 (70%) had IIIB, and 32 (14%) had IIIC. 96 (41%) had high risk (HR) disease, 11/96 (11%) patients were recommended 3 months of therapy and 81/96 (84%) were recommended 6 months. 138 patients (59%) were LR, of which 48/138 (35%) were recommended 3 months of therapy and 81/138 (59%) were recommended 6 months. Thus, 59/234 (25%) patients were recommended to proceed with only 3 months of therapy (see table). 215/234 patients (92%) received adjuvant therapy (2 died prior to treatment start, 8 were not treated due to age or poor performance status, 1 had financial issues, 6 refused, 2 were lost to follow-up). 57 patients received or were planned for CAPOX, 114 for FOLFOX, 41 for CAP, and 9 for 5-FU. Treatment started a mean of 7 weeks post-op. 108/215 patients (50%) required dose interruptions, while 85 (40%) required dose reductions and 14 (7%) switched regimens. 164 patients (76%) completed the full duration with some therapy. 41 patients had a recurrence/progression (34 actually received adjuvant therapy). Conclusions: Among 234 patients with stage III colon cancer intended for adjuvant therapy in a large community practice, 25% were planned for or treated with 3 months vs 6. Of those that initiated therapy, 76% completed treatment. The results of the IDEA trial have influenced decision making for community oncologists. While only a quarter implemented shorter durations of treatment, we expect that this rate will increase as improved patient outcomes are demonstrated. [Table: see text]
Preoperative radiotherapy for select T4 primary and locally recurrent colon cancers: Experience from an Australian quaternary centre.
Authors: Agas Ryan Anthony Francisco , Gosavi Rathin Ryan , Fahey Michael T , Ngan Samuel Y 
Published: June 2023

e15656 Background: We report our experience with preoperative radiotherapy for select T4 primary or locally recurrent colon cancers in a single, quaternary institution. Methods: A total of 89 patients with T4 primary (n = 40) and locally recurrent (n = 49) adenocarcinoma of the colon ( > 15 cm from the anal verge) underwent preoperative-intent radiotherapy in our centre from 2005 to 2020. Majority of the tumours arose from the sigmoid, 79% (n = 29) for the T4 primary group and 68% (n = 32) for the locally recurrent group. The most common tumour sites prior to preoperative radiotherapy in the locally recurrent group were the lateral pelvic brim (n = 24; left = 16; right = 8), and the proximal presacral area (n = 13). Of the evaluable patients, 95.8% (23/24) of the T4 primary group and 91.3% (21/23) of the locally recurrent group were MMR-proficient. Preoperative radiotherapy prescription was 45-50.4 Gy given in 1.8-2 Gy per fraction. Concurrent 5-FU based chemotherapy was given in 95% (n = 38) of the T4 primary group and 95.9% (n = 47) locally recurrent group. Median follow-up time was 48.9 months (range, 31.5- 80.7) for the T4 primary group and 43.1 months (range, 24.2- 74.1) for the locally recurrent group. Results: In the T4 primary group, downstaging of the pre-treatment clinical stage was documented in 57.5% (n = 23) and curative-intent surgery was possible in 90% (n = 36), 80.5% (n = 29) of which were R0 resections. On the other hand, curative-intent surgery was possible in 79.6% (n = 39) of the locally recurrent group, 64% (n = 25) of which were R0 resections. Of the patients who underwent surgery, 22% (n = 8) in the T4 primary group and 41% (n = 16) in the locally recurrent group avoided a multi-visceral resection. A pathologic complete response was achieved in 8.3% (n = 3) in the T4 primary group and in 10.3% (n = 4) in the locally recurrent group. For the T4 primary group, 13% had local failures (Hazard rate 3%, 95% CI 1-6%), 38% had any disease progression (Hazard Rate 9%; 95% CI 5-14), and 45% died (Hazard Rate 8%; 95% CI 5-13) during the follow-up period. For the locally recurrent group, 35% had local failures (Hazard Rate 13%, 95 CI 9-19), 61% had any disease progression (Hazard Rate 20%, 95% CI 14-29), and 60% died (13%, 95% CI 9-19) the follow-up period. Grade 1-2 anastomotic leak occurred in a total of 6 (8%) patients, 3 in each group. Readmission after surgery was needed in a total of 17 (22.6%) patients, 4 in the T4 primary group and 13 in the locally recurrent group. There was no 30-day mortality in the entire cohort. Conclusions: Curative-intent resection may be achieved after preoperative radiotherapy for select T4 primary and locally recurrent colon cancer, which may translate in encouraging clinical outcomes for an advanced cohort of patients. Careful patient selection is required to identify which colon cancer patients may benefit with preoperative radiotherapy.
Development and validation of a clinical prognostic model for BRAF V600E mutated colorectal cancer patients based on pathological stage, microsatellite status, and primary tumor site.
Authors: Ou Kai , Yang Lin 
Published: June 2023

e15660 Background: Colorectal cancer patients with BRAF V600E mutations may be a heterogeneous population with different outcomes. Clinical and molecular pathologic factors related to the prognosis of colorectal cancer need further investigation. Methods: The clinical and pathological information of 206 patients with BRAF V600E mutated colorectal cancer diagnosed in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from 2014 to 2021 was retrospectively collected. LASSO regression, COX regression and Nomograms were used to develop clinical prognostic models. The differentiation was measured by C-statistic and decision curve analysis, and the predicted variability was evaluated by calibration curve. The prognostic model was externally validated with validation set data from 164 patients pooled from 5 studies. Results: Our clinical prognostic model included three variables: pathological stage, microsatellite status, and primary tumor site. In internal validation, the model had a concordant index of 0.785 (95%CI [0.732-0.839]) and a concordant index of 0.754 (95%CI [0.698-0.810]) using pathological staging. External validation confirmed the robustness of the model with a consistency index of 0.670 (95%CI ([0.617-0.724]) and a consistency index of 0.584 (95%CI [0.546-0.622]) using pathological staging. The application of decision curve analysis in both the training set and the validation set showed that our three-factor clinical prediction model was superior to the pathological staging. The calibration graph drawn based on the prediction and the actual situation is close to the 45° diagonal. Conclusions: By adding microsatellite status and primary tumor site on the basis of pathological stage, we improved the discriminability and prediction accuracy of the model, and successfully established a prognosis model for patients with BRAF V600E mutation of colorectal cancer.
Effect of hypoxic status on survival and therapeutic responses in gastric cancer.
Authors: Dai Chan , Duan Xiaohong , Yang Chunyan , Zhou Qiming , Pei Zhihua , Wang Dongliang , Fang Yueyu 
Published: June 2023

e16003 Background: As a significant factor of tumor microenvironment (TME), hypoxia is closely related to cancer metastasis, immune escape and drug resistance. The potential prognosis of hypoxia, as well as its influence on the TME, and therapeutic response have not yet been comprehensively studied in gastric cancer (GC). Here, we developed a prognosis risk assessment model (hypoxia_pred model) based on genes related to hypoxia, and further explored the exact role an impact of hypoxia in GC. Methods: Clinical information and gene expression profile were obtained from Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA). 375 patients from TCGA-STAD cohort were used as training set. A 21-hypoxic genes expression dataset from TCGA-STAD was performed an unsupervised clustering analysis for different molecular subtypes of GC. Genes associated prognosis were screened by univariate Cox analysis with a cutoff of pvalue＜0.05. The prognostic risk model based on 9-genes transcriptome data of both hypoxia and prognosis related genes was constructed by Least Absolute Shrinkage and Selection Operator regression analysis. Another two gene expression datasets including 409 patients from GEO (GSE62254 and GSE26901) were employed for verifying the forecast performance of this model. In addition, we used ESTATE and single sample Gene Set Enrichment Analysis (ssGSEA) to explore tumor immune infiltration and potential molecular mechanism of hypoxia in GC. We also evaluated the influence of hypoxia on the prognosis, targeted therapy and immunotherapy of GC patients by survival analysis, targeted drug sensitivity analysis and the assessments of the Cancer Immunome Atlas database. Results: We found hypoxia_pred model is a valuable predictor for the survival of GC in validation cohort (AUC > 0.7). AUC for 1- and 3-year overall survival of GC patients in the TCGA cohort were 0.71 and 0.73. In GC, it was supposed that the aggravation of hypoxia was accompanied by the increase of immune rejection phenotype and the infiltration of immunosuppressive cells. In the validation set, patients predicted high risk by the model have worse immunotherapeutic response and prognosis, and may profit from drugs that inhibit cell cycle signaling pathways. In addition, the outcomes by hypoxia_pred for changes in TME, efficacy of immunotherapy and drug sensitivity were quite hypoxia_pred. targeted drug sensitivity, immune microenvironment, biological function, immunotherapeutic response, and immune cell infiltration were found to be significantly different in those molecular subtypes and risk groups. Conclusions: The model based on hypoxic environment provides theoretical foundation for predicting tumor prognosis and clinical treatment, and may improve the prognosis of GC patients by recommending personalized immunotherapy.
Efficacy and safety of second-line treatment for advanced gastric cancer: A network meta-analysis of randomized controlled trials.
Authors: Ma Xiaoting , Yang Lin 
Published: June 2023

e16018 Background: To evaluate the difference of curative effect between different treatment regimens in patients with advanced gastric cancer (AGC) who have previously received fluorouracil based first-line chemotherapy. Methods: We searched PubMed, PMC and EMBASE databases for published randomized controlled trials (RCTs). The number of people who reached the objective response rate (ORR) and the hazard ratio (HR) and its 95% confidence interval (CI) of progression-free survival (PFS) and overall survival (OS) were extracted. R (version 4.0.5) and R Studio were used to conduct meta-analysis of relevant data based on the Bayesian framework. Gemtc software package facilitates statistical analysis. To provide a ranking for each treatment regimen, surface under the cumulative ranking curve (SUCRA) was calculated. Survival analysis was conducted based on WinBUGS 14. STATA17.0 was used to draw the network diagram and funnel plot. Results: A total of 17 RCTs were included in this meta-analysis, and a total of 15 treatment regimens were used in the second-line treatment of AGC. There was no publication bias or other bias in the studies. Ramucirumab combined with paclitaxel and nab-paclitaxel weekly regimens have obvious advantages in efficacy and safety. Among them, ramucirumab combined with paclitaxel (83.6%) has great advantages in ORR, while the probability of anemia (36.6%) and anorexia (22.7%) is low, and the probability of leucopenia (66.6%) is high. However, the ORR of nab-paclitaxel weekly regimen (71.4%) is only second to that of ramucirumab combined with paclitaxel, and the probability of anemia (46.3%) and anorexia (44%) is also low, and the probability of leucopenia (53.8%) is high. In terms of OS and PFS, ramucirumab combined with paclitaxel has the best effect according to the probabilistic settlement table. Pembrolizumab and 5-Fu have poor therapeutic effects in terms of PFS. Conclusions: Ramucirumab combined with paclitaxel and nab-paclitaxel can significantly improve the survival outcome of patients with AGC. The effect of ramucirumab combined with paclitaxel is significantly better than that of paclitaxel, and the effect of nab-paclitaxel is only second to that of ramucirumab combined with paclitaxel. The safety of multi-drug combination should also be carefully considered. These findings may help clinicians better choose the second-line treatment strategy for patients with AGC.
Predictors of resistance to trastuzumab deruxtecan (T-DXd) in esophagogastric adenocarcinoma (EGC).
Authors: Tsai Charlton , Chou Joanne F. , Biachi de Castria Tiago , Tang Laura H. , Ilson David H. , Ku Geoffrey Yuyat , Schultz Nikolaus , Capanu Marinela , Janjigian Yelena Y. , Maron Steven Brad 
Published: June 2023

e16024 Background: In DESTINY-Gastric01/02, T-DXd improved objective response rates (ORR) and overall survival (OS) relative to chemotherapy in patients (pts) with trastuzumab-refractory HER2+ EGC. We sought to identify clinicopathologic features that predict response and resistance to T-DXd, in a cohort from Memorial Sloan Kettering Cancer Center (MSKCC). Methods: Demographics of pts with HER2+ (HER2 IHC 3+ or IHC 2+/FISH+) advanced EGC at MSKCC treated with T-DXd in 2nd line or later (2L+) from 2017 to 2022 were reviewed via the medical record. Progression-free survival (PFS) and OS were calculated from T-DXd initiation to event or last follow up. Univariate (UV) and multivariable (MV) analyses of PFS were performed using Cox proportional hazards models. Categorical comparisons used the χ2 or Fisher’s exact test when subgroup n < 5. Results: 57 pts received 2L+ T-DXd (25 2L, 18 3L, 14 4L+). Median age at treatment was 64.5 years and most pts were male (74%) and white (82%) with primary tumors in the esophagus/GE junction (72%) and HER2 IHC 3+ expression (82%). With median follow up of 12 months (mos), ORR was 49% with median PFS (mPFS) of 5.4 mos (95% CI 3.2 – 6.8) and median OS (mOS) of 13 mos (95% CI 8.5 – 19). Pts with HER2 IHC 2+ EGC had lower ORR (30% vs 53%, p = 0.3) and inferior PFS compared to IHC 3+ in UV analysis (HR 2.58, 95% CI 1.08 – 6.13 mos, p = 0.03). Pts with HER2 retesting (n = 22) within 1 mo prior to T-DXd had higher ORR (64% vs 40%, p = 0.08); HER2 IHC in 4 of these pts decreased from 3+ to 2+. Despite irinotecan (irino) ORR of 38% prior to T-DXd in 8 pts, only 1 (12%) had OR to T-DXd. Furthermore, only one of the 12 pts (8%) who received irino following T-DXd had OR to irino, despite T-DXd ORR of 42% among these pts. Irino-treated pts also had worse PFS on T-DXd (vs no prior irino, HR 4.91, 95% CI 2.09 – 11.5 mos, p < 0.001). Prior checkpoint inhibition was not associated with PFS on T-DXd. In MV analysis, prior irino therapy remained significantly associated with progression/death (HR 4.12, 95% CI 1.63 – 10.4 mos, p = 0.003), and not HER2 IHC 2+ (vs 3+) nor 3L+ treatment (vs 2L). Additional correlations with genomic alterations will be presented. Conclusions: Consistent with DESTINY-Gastric trials, approximately half of pts with EGC at MSKCC had OR to T-DXd with mOS > 1 year. However, our real-world findings suggesting lower ORR in patients with sequential T-DXd and irinotecan-containing therapy and those without pre-T-DXd HER2 IHC confirmation merit further validation in future studies.
Efficacy and safety of camrelizumab combined with apatinib in the treatment of advanced gastric cancer: Preliminary results from a multicenter, prospective study.
Authors: He Yifu , Hu Bing , Liu Ke , Cheng Xiaofei , Cheng Huaidong , Chen Mo , Hu Changlu , Li Chenghui , Mei Xinkuan , Liu Jianfeng , Liu Hu , Wang Gang , Li Hongxia , Zhang Dingqing , Luo Huiqin 
Published: June 2023

e16035 Background: There is an urgent need to find new therapeutic drugs/regimens for advanced gastric cancer. Camrelizumab combined with apatinib and chemotherapy has shown a high objective response rate and survival benefit in the first- and second-line treatment of advanced gastric cancer. Therefore, we conducted a prospective, observational study to analyze the efficacy and safety of camrelizumab combined with apatinib and chemotherapy in the first- and second-line treatment of advanced gastric cancer. Methods: This was a multicenter, observational study enrolling patients aged ≥ 18 years with an ECOG PS of 0-2 and pathologically or histologically confirmed advanced gastric cancer. Results: By January 9, 2023, 207 patients with advanced gastric cancer from 32 centers were enrolled. Most patients were male (138 [66.7%]), stage IV (151 [72.9%]), and ECOG PS of 1 (145 [70.0%]) with a median age of 66 years. The degree of differentiation was mainly moderate and low (155 [74.9%]). 109 patients (52.7%) had a surgical history of the primary lesion, 123 (59.4%) had previously received chemotherapy, and 115 (55.6%) had received COVID-19 vaccine. The first-line treatment included camrelizumab plus chemotherapy for 4-6 cycles followed by apatinib in 68 patients (32.9%), and camrelizumab plus chemotherapy and apatinib in 51 (24.6%). Second-line treatment included camrelizumab plus apatinib for 35 patients (16.9%), chemotherapy and apatinib for 44 (21.3%), and other treatments for 9 (4.3%). Clinical efficacy was evaluated in 52 patients. There were 20 patients with partial response, 26 with stable disease, and 6 with progressive disease. The overall objective response rate (ORR) was 38.46% and disease control rate (DCR) was 88.46%. The ORR and DCR in the first-line setting were 50.00% and 100.00%, and ORR and DCR in the second-line setting were 16.67% and 66.67%. Furthermore, the ORR was 40.63% and the DCR was 90.63% in patients vaccinated against COVID-19 compared to 40.00% and 85% in unvaccinated patients. The median PFS and OS have not been reached. The incidence of adverse events (AEs) was 80.4% and the incidence of grade≥3 AEs was 3.5%. The most common AEs were reactive cutaneous capillary endothelial proliferation (71.3%), nausea (51.0%), leukocyte reduction (38.46%), and hypertension (13.3%). Conclusions: In this real-world study of gastric cancer, the first-line treatment showed good efficacy, suggesting early administration with combination treatment may bring more benefits to the patients. Additionally, COVID-19 vaccination did not affect the efficacy of combination treatment. Further validation of these preliminary results is warranted. Clinical trial information: ChiCTR2200059650 .
Effect of MDSC-targeted TFF2-MSA with PD-1 blockade therapy in advanced gastric cancer models.
Authors: Qian Jin , Ryeom Sandra , Daugherty Bruce L , Lederman Seth M. , Wang Timothy C. 
Published: June 2023

e16037 Background: Recent studies revealed chemotherapy increases anti-PD1 response of gastric cancer (GC) by reducing myeloid-derived suppressor cells (MDSCs). However, a more specific MDSC-targeted treatment is needed to further improve anti-PD1 efficacy in advanced GC. Trefoil factor family 2 (TFF2), a partial agonist of CXCR4 and a secreted anti-inflammatory peptide, can suppress MDSC expansion. Here, we developed a novel MDSC-targeted peptide TFF2-MSA and investigated whether it can synergize with anti-PD1 in syngeneic GC mouse models. Methods: Murine serum albumin (MSA) was fused to murine TFF2 to generate TFF2-MSA peptide with an extended serum half-life. ACKP (Atp4b-Cre; Cdh1-/-; LSL-KrasG12D; Trp53-/-) GC cells developed from a highly malignant diffuse GC mouse model were grafted subcutaneously into HDC-GFP transgenic mice in which the immunosuppressive histidine decarboxylase (HDC)-expressing myeloid cells were traced with GFP. These recipient mice then received either TFF2-MSA or anti-PD-1 antibody or both when tumors reached 150 mm3. At the endpoint, flow cytometry analysis was performed to examine immune profiles. In parallel, a group of the s.c. tumor bearing mice were followed up for survival differences in response to the treatments. In the orthotopic model, ACKP-luc cells were implanted to stomach submucosa, and recipient mice received the same treatments started after 1 week. In the metastasis model, subcutaneous flank tumors were resected in ACKP-grafted mice once tumors reached 500 mm3 to permit spontaneous lung metastasis, and mice then received the same treatments. Results: While either TFF2-MSA or PD-1 antibody showed little benefit as a single agent (TGI 15% and 25% respectively, p>0.05), their combination dramatically suppressed ACKP s.c. tumor growth (TGI 78%, p<0.0001) and markedly prolonged median survival (64 days vs. 32.5 days in control) in a synergistic manner. The combination therapy efficiently reduced tumor HDC-GFP+ MDSCs by 67%, and profoundly increased tumor-infiltrating cytotoxic CD8+ T cells by 18 fold. The myeloid/lymphoid progenitor and output ratio in the bone marrow were decreased by the combination, to a similar level of tumor-free mice. While standard chemotherapy (5-fluorouracil and oxaliplatin) showed no efficacy, adding chemotherapy to the combination further improved treatment efficacy (TGI 91%) and extended median survival to 73 days. In addition, in the orthotopic model, the TFF2-MSA/PD-1 antibody combination eradicated GC in 80% mice without recurrence compared to 0% with either monotherapy. Finally, the combination of TFF2-MSA/PD-1 antibody significantly reduced 80% lung metastasis (vs. control, p<0.0001), compared to minimal inhibition with either monotherapy (p>0.05). Conclusions: Targeting MDSCs using TFF2-MSA synergizes with PD-1 blockade therapy in advanced and metastatic syngeneic mouse models of gastric cancer.