bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient perspectives on colorectal cancer care delivery during the COVID-19 pandemic: A qualitative interview study.
Authors: Wilson Rozanne , Vieira Maria Cecilia , Roach Meaghan , Prood Nadya , Belani Anjali , Mesana Laura , May Suepattra Grace
Published: January 2023

33

Background: The COVID-19 pandemic generated unprecedented interruptions and impacts on healthcare services across the US, including cancer care delivery. Patient perspectives on navigating colorectal cancer (CRC) care throughout the pandemic have not been well documented. This study explored patient experiences and perspectives around CRC care delivery throughout the pandemic by examining the impacts of COVID-19 on planned treatment, healthcare access, and quality of care. Methods: Patients diagnosed with CRC prior to January 2020 and who received treatment for CRC during 2019 participated in this qualitative study. Semi-structured interviews explored treatment experiences before and during the pandemic and were conducted between December 2021 and March 2022. Thematic analysis was used to identify key themes. Results: Twenty-four patients with CRC (mean age 45.4 years [SD=9.7]; 75% female; 62.5% current stage IV) completed an interview. Participants reported diminished mental health as the most salient impact of the pandemic related to their CRC care. Participants expressed how difficult, isolating, and lonely they felt navigating cancer treatment, particularly as a result of visitor restriction policies that did not allow their support person (e.g., spouse) to be present during visits or stays. Increased anxiety, fear, and worry over how the pandemic may affect their planned cancer care, including fear of contracting the virus themselves, were major concerns. Other impacts experienced included barriers to physically accessing care facilities (e.g., reduced appointment availability, staffing shortages), delays to patients’ planned treatment (e.g., canceled surgery), and increased access to and use of telehealth, which was perceived as being more convenient and safer than in-person visits. Participant perspectives on the quality of care they received throughout the pandemic were based on frequency and personalization of patient-provider communication, ability to access their usual care and support services (e.g., care navigators, support groups), and provider attention to their mental health. To improve the quality of cancer care in a pandemic setting, participants recommended personalized and frequent communications from the oncology care team, holistic care that includes mental health support, and streamlined insurance preauthorization processes. Conclusions: While the long-term impacts of COVID-19 on CRC care delivery have yet to be fully understood, this study highlights the key challenges patients experienced while receiving CRC care during the pandemic. Recognizing the strain of the pandemic on patients’ mental health and well-being will help to ensure patient-provider communication and support services consider the short and long-term effects of the pandemic for cancer patients as well as help contribute to improved treatment-related outcomes.
Docetaxel-based triplet neoadjuvant therapy for esophageal adenocarcinoma: A comprehensive analysis of outcomes spanning over a decade.
Authors: Tankel James , Ahmed Nabeel , Alcindor Thierry , Asselah Jamil , Kavan Petr , Lemay Frederic , Frechette Dominique A. , Sud Shelly , Lee Lawrence , Najmeh Sara , Spicer Jonathan , Cools-Lartigue Jonathan , Mueller Carmen L. , Ferri Lorenzo
Published: January 2023

332

Background: Docetaxel-based therapy is currently the most effective neoadjuvant regimen for locally advanced gastroesophageal adenocarcinoma. However, prior trials were primarily designed to target gastric cancer. As survival associated with taxane-based chemotherapy in esophageal adenocarcinoma (EAC) is less well described, we sought to review our experience with docetaxel based therapy as a neoadjuvant approach for EAC. Methods: A single centre retrospective review of a prospectively maintained upper GI cancer surgical database was performed (2008-2021). Patients with EAC undergoing curative intent neoadjuvant therapy with two similar docetaxel-based regimens (DCF - Docetaxel/Cisplatin/5FU or FLOT - 5FU, Leucovorin, Oxaliplatin, and Docetaxel) followed by en-bloc resection were included. Gastric/EGJ type III tumors were excluded. Clinicopathological data and overall survival (OS) were recorded and stratified by chemotherapy type (DCF vs FLOT). Data are presented as median (+/-SD). Mann-Whitney U tests for continuous or Fischer exact test for categorical variables determined significance. Kaplan-Meier curves compared OS. Results: 225 EAC patients were identified: Age 64.2 (±10.3) and tumor location was Esophageal/EGJ I/EGJ II (106/33/86). Clinical stage was cT3-4 in 201/225 (89.3%) and most were cN+ (200/225: 88.9%). There were 121 (53.7%) treated with neoadjuvant DCF whilst 104 (46.3%) received FLOT. All pre-op cycles were completed in 181 (80.4%) and did not differ between DCF and FLOT (81.8% vs 78.8% - NS). Operative procedure included Ivor Lewis in 188 (83.5%), left thoraco-abdominal esophagectomy in 20 (8.8%), and McKeown in 17 (7.5%) and also did not differ between DCF and FLOT. In terms of pathologic outcomes, the median lymph node yield was 35 (±16) of which 3.6±5.8 were positive). There was no difference when comparing between regimens. There were 134 (59.6%) patients ypN1-3 (DCF=76(62.8%) vs FLOT=58(55.8%)- NS). An R0 resection was achieved in 210 (93%) patients (DCF=92.6% vs FLOT=94.2%- NS). Complete pathological response (no residual cancer) was found in 21 patients (9.3%) (DCF=14(11.6%) vs FLOT=7(6.7%) – NS). At follow up of 41(±36) months (DCF= 52±41 vs FLOT=27±23 - p<0.001) OS (KM curve Fig 1) at 1, 3 and 5 years for the entire cohort was 91.4%, 62.8%, and 55.7%, with no difference between DCF (92.3%/68.8%/59.5%) and FLOT (89.8%/54.5%/51.7% - NS). Conclusions: This retrospective review, the largest yet reported, demonstrates that these similar docetaxel-based neoadjuvant chemotherapy regimens are highly effective for patients with locally advanced esophageal adenocarcinoma.
Role of pretreatment absolute lymphocyte count in survival outcomes for esophageal cancer treated with neoadjuvant chemoradiotherapy and pembrolizumab: An analysis from a prospective cohort.
Authors: Qi Weixiang , Wang Xiaoyan , Chen Jiayi , Zhao Shengguang , Li Hecheng
Published: January 2023

338

Background: To analyze the relationship between pre-treatment inflammatory biomarkers (IBs) and survival outcomes for ESCC treated with neo-CRT and pembrolizumab. Methods: Clinical variables and IBs [absolute monocyte count (AMC), absolute lymphocyte count (ALC), platelet count (PLT), neutrophil lymphocyte ratio (NLR), Platelet lymphocyte ratio (PLR), Lymphocyte monocyte ratio (LMR), Pan-Immune Inflammation value (PIV), Systemic immunoinflammatory index (SII), Systemic Immunoreactivity Index (SIRI) and prognostic nutritional index (PNI)] were collected from two prospective trials. Univariate and multivariate analysis was performed. Results: A total of 51 patients were included. Of them, 35 patients achieved pathologic complete response after neo-CRT and pembrolizumab (pCR: 68.6%). With a median follow-up of 20 months, the two-year PFS and OS of the cohort was 64% and 91%, respectively. Multivariate logistic regression analysis indicated that ALC (OR 4.4, p=0.051) and PLT (OR 6.7, p=0.023) were two independent predictors for achieving pCR among ESCC treated with neo-CRT and pembrolizumab. Multivariate Cox regression analysis showed that ALC (HR 0.27, p=0.028) and SIRI (HR 3.13, p=0.048) were two independent predictors for PFS of this patient population. K-M analysis demonstrated that the PFS of ESCC with high base line ALC was significantly better than those with low ALC (2-year PFS: 77% vs. 47%, p=0.027), but not for overall survival (2-year OS: 96% vs. 87%, p=0.46). Conclusions: Our data demonstrates that pre-treatment ALC is an independent predictor for archiving pCR and favorable outcomes of ESCC treated with neo-CRT and pembrolizumab. Clinical trial information: NCT04435197 ; NCT04435197 .[Table: see text]
The new prognostic index of advanced gastric cancer using the data from JCOG1013.
Authors: Takahari Daisuke , Boku Narikazu , Iwasa Satoru , Mizusawa Junki , Hashimoto Tadayoshi , Yoshikawa Takaki , Kadowaki Shigenori , Machida Nozomu , Ishido Kenji , Tsuda Masahiro , Kinoshita Takahiro , Yasuda Takushi , Chin Keisho , Hata Hiroaki , Ojima Toshiyasu , Yamada Yasuhide , Terashima Masanori
Published: January 2023

342

Background: We previously reported that performance status (PS) ≥1, no prior gastrectomy, number of metastatic sites ≥2, and high serum ALP level are poor prognosis factors and proposed a JCOG prognostic index by analyzing the data of advanced gastric cancer (AGC) patients enrolled in JCOG9912 (Takahari D et al. Oncologist 2014). Recently, Neutrocyte/ Lymphocyte Ratio (NLR) and diffuse type of cancer have also been reported to be prognostic factors of AGC. Methods: Prognostic factors were assessed in patients with AGC who enrolled in JCOG1013, the phase III study comparing docetaxel, cisplatin, and S-1 (DCS) versus cisplatin and S-1 (CS) in first-line treatment (Yamada Y et al. Lancet Gastroenterol Hepatol. 2019) was retrospectively evaluated using a Cox proportional regression model. The overall adequacy of risk prediction in the modified JCOG prognostic index and the original index were assessed by C-statistics. Results: Among 741 patients, 730 with all data for this analysis were selected. The median overall survival (OS) was 14.9 months (95% confidence interval [CI], 14.1–15.8). The median OS of the good (n=233), moderate (n=444), and poor (n=53) risk groups by the original JCOG index was 19.0, 14.2, and 9.1 months, respectively. The HRs compared with the good group were 1.59 [95% CI, 1.33–1.89; p < 0.0001] in the moderate group, and 2.47 [95% CI, 1.81–3.38; p < 0.0001] in the poor group with C-statistics of 0.572. In the multivariable analysis of 7 factors which showed p<0.1 in univariable analysis, PS ≥1 (hazard ratio [HR], 1.490; 95% CI, 1.264–1.755; p < 0.0001), diffuse type (HR, 1.337; 95% CI, 1.122–1.594; p = 0.012), number of metastatic sites ≥2 (HR, 1.256; 95% CI, 1.058–1.492; p = 0.0093), and NLR≥3.1 (HR, 1.539; 95% CI, 1.309–1.809; p < 0.0001) were significantly associated with worse prognosis, whereas no prior gastrectomy, peritoneal metastasis, and high serum ALP level were not. As the modified JCOG prognostic index, patients were classified into three groups according to the number of these four newly identified prognostic risk factors: good (no), moderate (1 or 2), and poor (3 or 4). Median OS of the good (n=221), moderate (n=441), and poor (n=68) risk groups was 20.6, 13.7, and 9.4 months, respectively. The HRs compared with the good group were 1.70 [95% CI, 1.42–2.03; p < 0.0001] in the moderate group, and 3.11 [95% CI, 2.33–4.14; p < 0.0001] in the poor group with C-statistics of 0.591. Three groups by the modified JCOG prognostic index also showed clear separation of OS in either subgroup of DCS or CS. Conclusions: Modified JCOG prognostic index, including NLR ≥3.1 and diffuse type instead of no prior gastrectomy and high serum ALP level, showed clear stratification of OS in JCOG1013.
Advantages of minimally invasive surgery for remnant gastric cancer: A multi-institutional cohort study.
Authors: Aoyama Ryuhei , Tsunoda Shigeru , Okamura Ryosuke , Yamashita Yoshito , Hata Hiroaki , Kinjo Yousuke , Miki Akira , Kanaya Seiichiro , Yamamoto Michihiro , Matsuo Koichi , Manaka Dai , Itami Atsushi , Kan Takatsugu , Ito Tetsuo , Hirai Kenjiro , Hosogi Hisahiro , Nishigori Tatsuto , Hisamori Shigeo , Hoshino Nobuaki , Obama Kazutaka
Published: January 2023

357

Background: Remnant gastric cancer (RGC) is defined as a cancer arising in the remnant stomach after initial gastrectomy, regardless of the previous disease or surgical procedure. Despite growing evidence of the effectiveness of minimally invasive surgery (MIS) for primary gastric cancer, MIS for RGC remains controversial due to the rarity of the disease. This study aimed to evaluate the surgical and oncological outcomes of MIS for radical resection of RGC. Methods: We collected the data of patients with RGC who underwent surgery with curative intent between 2005 and 2020 from 17 institutions in Japan, and performed a propensity score (PS) matching analysis to compare the short- and long-term outcomes of MIS with open surgery. Results: A total of 327 patients were included in this study and 186 patients were analyzed after matching. The risk ratios for overall and severe complications were 0.76 (95% confidence interval [CI]: 0.45–1.27) and 0.65 (95% CI: 0.32–1.29), respectively. The MIS group had significantly less blood loss (50 ml vs. 361 ml, P<0.001) and a shorter hospital stay (13 days vs. 16 days, P=0.009) than the open surgery group, while the operative time was longer in the MIS group (344 min vs. 273 min, P<0.001). The median follow-up duration of this cohort was 4.6 years, and the 3-year overall survival rates were 77.9% in the MIS group and 76.2% in the open surgery group (hazard ratio [HR], 0.78; 95% CI: 0.45–1.36). The 3-year relapse-free survival rates were 71.9% in the MIS group and 62.2% in the open surgery group (HR, 0.71; 95% CI: 0.44–1.16). Locoregional recurrence occurred in three patients (3.2%) in the MIS group and four patients (4.3%) in the open surgery group. There were also no differences in the other patterns of recurrence between the groups. Conclusions: MIS for RGC showed favorable short- and long-term outcomes compared to open surgery. MIS is a promising option for radical surgery for RGC.
Safety and efficacy of prophylactic pegfilgrastim on day 3 of neoadjuvant DCF chemotherapy in elderly patients with resectable esophageal cancer.
Authors: Ikeda Go , Yoshinami Yuri , Kadono Toru , Hirose Toshiharu , Ohara Akihiro , Itoyama Mai , Azuma Ikuko , Yamamoto Shun , Honma Yoshitaka , Ishiyama Koshiro , Oguma Jyunya , Daiko Hiroyuki , Kato Ken
Published: January 2023

375

Background: Neoadjuvant chemotherapy with docetaxel, cisplatin plus 5-FU (Neo DCF) is one of the standard treatment for resectable esophageal cancer (EC) based on the results of the JCOG1109 study, however, a high frequency (5-30%) of febrile neutropenia (FN) has been reported with NeoDCF and the elderly (patients) pts have higher risk for FN. A single arm phase II study indicated that use of primary prophylactic pegfilgrastim (PG) on day 3 of NeoDCF might prevent FN. We compared the frequency of neutropenia and FN with or without primary prophylactic administration of PG on day 3 of NeoDCF in elderly resectable EC pts. Methods: EC pts who had received NeoDCF between 2009 and 2022, were ≥70 years old, and had adequate organ functions and PS were selected for this retrospective study. Pts were divided into two groups with Day 3 PG-containing DCF (day3 prophylactic PG: D3PG) or No PG DCF (non-prophylactic PG: NPG). Three courses of DCF (DTX [day 1]: 70 mg/m2, CDDP [day 1]: 70 mg/m2, 5-FU [continuous infusion on days 1-5]: 750 mg/m2, every 3 weeks) were planned, and prophylactic antibiotics was administered on days 5-15 in each group if possible. We retrospectively evaluated the relative dose intensity (RDI), histopathological and clinical benefit, and adverse events. Results: A total of 67 pts (D3PG, 32; NPG, 35) with a median age of 73 years were identified. The PS (0/1/2) and clinical stage (I-II/III/ IVA-B [only supraclavicular lymph node]) were 18 (56.3%)/12 (37.5%)/2 (6.2%) and 1 (3.1%)/18 (56.3%)/13 (40.6%) in the D3PG group and 20 (57.1%)/15 (42.9%)/0 and 7 (20.0%)/24 (68.6%)/4 (11.4%) in the NPG group, respectively. Six pts in the D3PG group and 3 pts in the NPG group discontinued NeoDCF because of toxicity and progression. All pts except 1 in the D3PG group underwent surgery. The RDIs (DTX/CDDP/5-FU) were 0.90/0.83/0.90 in the D3PG group and 0.83/0.83/0.83 in the NPG group. Pts who achieved a pCR (D3PG/NPG) were 7/3 (22.6%/28.6%). The common grade ≥3 adverse events (D3PG/NPG) were neutropenia (12.5%/71.4%) and FN (6.3%/20.0%). Three-year relapse-free survival rate (D3PG/NPG) was 70.8%/54.4% (hazard ratio [HR] 0.525 [95% confidence interval (CI) 0.189-1.457], p=0.216). Three-year survival rate (D3PG/NPG) was 91.8%/70.5% (HR 0.497 [95%CI 0.104-2.35], p=0.378), respectively. Conclusions: The use of primary prophylactic PG on day 3 of preoperative DCF improved the safety and maintained the RDI in the D3PG group. The efficacy was comparable between the D3PG and NPG groups despite the higher number of pts with more advanced disease in the D3PG group.
Updated results of paclitaxel and cisplatin in combination with anlotinib as first-line treatment for patients with advanced ESCC: A multicenter, single-arm, open-label phase II clinical trial.
Authors: Li Ning , Wu Tao , Hong Yong-Gui , Guo Yanzhen , Cheng Yufeng , Li Baosheng , Wang Junsheng , Luo Suxia
Published: January 2023

376

Background: Paclitaxel combined with cisplatin regimen has been the standard of care as first-line therapy in advanced ESCC for almost two decades. PD-1 blockades combined with chemotherapy as first line setting exhibited superior efficacy for patients with ESCC recently. Anlotinib was a potential second-line monotherapy for patients with ESCC in China. Therefore, this study was designed to explore the efficacy and safety of paclitaxel and cisplatin combined with anlotinib as first-line therapy in advanced ESCC. The study had been reported in 2020 ESMO (Abs 1448), 2021 ASCO-GI Symposium (Abs 181), 2021 ASCO (e16013), 2021 ESMO (Abs 1805) and 2022 ASCO-GI Symposium (Abs 315) consecutively and the update results were reported here. Methods: Patients with previously untreated metastatic or locally advanced ESCC were recruited and were given paclitaxel (135mg/m2, iv, q3w) and cisplatin (60~75mg/m2, iv, d1~3, q3w) plus anlotinib (10mg, po, d1~14, q3w) for 4~6 cycles as initial therapy. For those who did not have PD, maintenance treatment was adopted with anlotinib monotherapy (10mg, po, d1~14, q3w) until PD or unacceptable toxicity. The tumor response was assessed according to RECIST 1.1 using CT scans every two cycles. The predefined sample size was 47. Primary endpoint was PFS and secondary endpoints included safety, ORR, DCR and DOR. Results: From Oct 2019 to Mar 2021, a total of 47 patients were enrolled, 46 patients included in per-protocol set analysis. The best overall response indicated that there were 4 CR (8.7%), 31 PR (67.4%), 7 SD (15.2%) and 4 NE (8.7%). Consequently, ORR was 76.1% (95%CI: 61.2%-87.4%) and DCR was 91.3% (95%CI: 79.2%-97.6%). At the data cut-off date on Jan 2022, The median PFS and median OS were 8.38 months (95% CI, 6.59-10.17) and 18.53 months (95% CI, 13.11-23.95), respectively. Additionally, safety profile exhibited that the regimen was tolerable. Common grade ≥3 adverse reactions were neutropenia (17.0%), bone marrow suppression (12.8%), nausea (10.6%), and vomiting (10.6%). Conclusions: Regimen of paclitaxel and cisplatin combined with anlotinib as first-line therapy for advanced ESCC exhibited encouraging efficacy and tolerable safety profile. And the conclusions needed to be confirmed in phase III clinical trials. Clinical trial information: NCT04063683 .
Retrospective analysis of drug intake affecting the intestinal microbiota and the therapeutic effects of chemotherapy on gastric cancer.
Authors: Nakamura Takeaki , Watanabe Ryosuke , Yamamura Takahiro , Harada Kazuaki , Kawamoto Yasuyuki , Yuki Satoshi , Sakamoto Naoya , Komatsu Yoshito
Published: January 2023

379

Background: Administration of some medications, such as antibiotics, antacids, and probiotic supplementation, may affects the treatment outcomes of immune checkpoint inhibitors (ICIs), through the change of gut microbiota in cancer patients. Even when ICIs are combined with cytotoxic chemotherapy (Chemo), a use of such medications is expected to be a potential biomarker. However, the impacts of medications that affect gut microbiota on the efficacy of Chemo alone is unclear. Methods: We retrospectively analyzed patients who received fluoropyrimidines and platinum-based therapy for advanced gastric cancer in our institutions between January 2010 and December 2019. Progression-free survival (PFS) and overall survival (OS) by history of antibiotic/antacid/probiotic supplementation, were analysed. Results: A total of 101 pts were analyzed. Median age was 66 years (range, 30-81), female/male; 36/65, 1st-line regimen SP/XP/SOX/XELOX/FOLFOX; 52/2/39/1/7. In all patients, The median PFS for first-line treatment was 5.8 months (95% CI: 5.0-7.3) and the median OS was 15.5 months (95% CI: 12.5-18.6).Univariate analysis for PFS of first-line treatment did not show a significant difference in antibiotic use (median 7.6 vs 5.5 months, HR: 0.79 [95%CI: 0.50-1.24], p=0.31), oral antacids (median 6.6 vs 5.8 months, HR: 0.96 [95%CI: 0.61-1.54], p=0.89) and probiotic supplementation (median 9.1 vs 5.5 months, HR: 0.7 [95%CI: 0.38-1.26], p=0.24). Similarly in OS, the use of antibiotics (median 18.4 versus 13.4 months, HR: 0.85 [95%CI: 0.53-1.37], p=0.49), oral antacids (median 16.3 vs 13.8 months, HR: 1.15 [95%CI: 0.70-1.88], p=0.58), and oral probiotic supplementation (median 20.2 vs 13.8 months, HR: 0.77 [95%CI: 0.42-1.40], p=0.40), with no statistically significant differences. Conclusions: In this study, there were no significant differences in PFS and OS between patients administered with or without antibiotics, antacids, or probiotic supplementation. Future studies are expected to investigate the impacts of these medications on the treatment outcomes of ICIs+Chemo combination.
Adjuvant nab-paclitaxel plus S-1 versus oxaliplatin plus capecitabine after curative D2 gastrectomy in patients with stage III gastric adenocarcinoma: a phase 3 open-label, randomized controlled trial
Authors: Pengfei Yu , Du Yian , Xu Zhiyuan , Yang Litao , Ying Jieer , Chen Ping , Wei Yunhai , Wu Yingjie , Yan Zhilong , Xu Hongtao , Zhang Xiaojing , Li Yong , Zheng Zhichao , Chen Zhiheng , Cheng Xiangdong
Published: January 2023

386

Background: Although adjuvant chemotherapy improvs the survival rate of stage III gastric cancer after curative D2 gastrectomy, the overall benefit is unsatisfactory. Therefore, the study was designed to evaluate the efficacy and safety of adjuvant nab-paclitaxel plus S-1 (AS) versus oxaliplatin plus capecitabine (CAPOX) in the treatment of stage III gastric adenocarcinoma (GAC) after curative D2 gastrectomy. Methods: This phase 3, open-label, randomized study was conducted in patients with stage III GAC after curative D2 gastrectomy. Patients were randomized (1:1) to receive adjuvant AS (100 mg/m2 nab-paclitaxel on days 1 and 8; 40-60 mg oral S-1 twice daily on days 1-14) or CAPOX (130 mg/m2 oxaliplatin on day 1; 1000 mg/m2 oral capecitabine twice daily on days 1-14), repeat every 3 weeks for 8 cycles. The primary endpoint was the 3-year disease-free survival (DFS) rate by intention-to-treat analysis. Secondary endpoints included overall survival (OS) and safety. Results: Between March 2020 and August 2022, 280 patients were screened and 233 were randomly assigned to study treatment (AS, 115; CAPOX, 118). The median age was 62 years (range, 27-77) in AS and 63 years (range, 35-75) in CAPOX. The pathological stages were 42.61% stage IIIA, 34.78% stage IIIB, and 22.61% stage IIIC in AS, while those of CAPOX were 47.46% stage IIIA, 30.51% stage IIIB, and 22.03% stage IIIC. The 1-year DFS rate was 89.0% in AS versus 76.9% in CAPOX. The 1-year OS rate was higher in AS versus CAPOX (100% vs. 95.5%). Seven (6.09%) in AS and 11 (9.32%) in CAPOX experienced recurrence during follow-up; thereinto, one in CAPOX confirmed recurrence with tumor markers and clinical manifestations. Recurrence sites in AS and CAPOX involved the peritoneum (1 vs. 4), locoregional (1 vs. 2), and distant (5 vs. 6), of which, certain patients had 2 simultaneously. Among 6 deaths in CAPOX, 3 died from GAC, 1 died from other diseases and 2 died from unknown. The median relative dose intensity was 96.91% for nab-paclitaxel and 88.00% for S-1 in AS, 82.77% for oxaliplatin and 79.36% for capecitabine in CAPOX. Certain patients in AS (38.26%) and CAPOX (22.03%) experienced grade 3/4 adverse events (AEs). The most common AEs in AS and CAPOX included anemia (20.96% vs. 19.63%), neutropenia (30.70% vs. 21.02%), and thrombocytopenia (1.10% vs. 15.47%). Conclusions: In this study, AS showed longer trends in the DFS rate, OS rate, and manageable safety profile in patients with stage III GAC after curative D2 gastrectomy compared with CAPOX, suggesting a potential therapeutic option for this population. Clinical trial information: NCT04135781 .
Survival results by the prospectively determined clinical staging for locally advanced gastric cancer: An ancillary study of JCOG1302A (JCOG1302A2).
Authors: Hayashi Tsutomu , Mizusawa Junki , Hashimoto Tadayoshi , Fukagawa Takeo , Makuuchi Rie , Hikage Makoto , Misawa Kazunari , Yamada Takanobu , Nomura Takashi , Kawachi Yasuyuki , Kinoshita Takahiro , Kawabata Ryohei , Yabusaki Hiroshi , Sano Takeshi , Sasako Mitsuru , Yoshikawa Takaki , Boku Narikazu , Terashima Masanori
Published: January 2023

392

Background: Recently, neoadjuvant chemotherapy has been recognized as a promising strategy to improve the survival of patients with advanced gastric cancer. On the other hand, given the adverse events and treatment cost of chemotherapy, the candidate for NAC should be limited to patients who can benefit from NAC. In fact, as previously reported, the proportion of pathological stage I tumors was 50.4% in cT2N0, 38.7% in cT2N(+), 26.7% in cT3N0, 10.6% in cT3N(+), 9.0% in cT4aN0, and 3.0% in cT4aN(+). Therefore, clinical staging before initiation of treatment is increasingly important for determining therapeutic strategy. However, the long-term survival stratified by the prospectively-determined clinical stage has not been fully investigated. Methods: Between July 2013 and November 2014, the JCOG1302A examined 1260 patients with a clinical diagnosis of cT2/T3/T4, cN0/N1/N2/N3, M0, except for diffuse large tumors like linitis plastica and extensive bulky nodal diseases according to the Japanese Classification of Gastric Carcinoma (3rd English edition). The cT diagnosis was made by upper gastrointestinal endoscopy and comprehensive findings on upper abdominal contrast CT scan with 1 or 5 mm slice thickness. Lymph nodes with a shortest dimension greater than 8 mm or a longest dimension greater than 10 mm were defined as positive for metastasis. In this follow-up study, the survival data by stratifying the clinical staging were evaluated. Results: Among 1260 patients, survival data of 1177 were analyzed. With a median follow-up for 821 surviving patients of 6.0 years, the 5y-OS was 82.1% (95% CI, 77.3-85.9) in cT2 (n=319), 72.7% (68.2-76.6) in cT3 (n=450), 60.0% (54.9-64.7) in cT4a (n=401), and 40.0% (5.2-75.3) in cT4b (n=6), while that was 78.0% (74.2-81.2) in cN0 (n=560), 70.6% (65.4-75.2) in cN1 (n=350), 59.1% (52.5-65.1) in cN2 (n=241), and 28.4% (12.7-46.5) in cN3 (n=26), respectively. When combined with cT and cN, 5y-OS was 83.5% (77.8-87.8) in cT2N0 (n=226), 77.2% (71.0-82.2) in cT3N0 (n=232), 66.8% (56.3-75.2) in cT4aN0 (n=100), 100% in cT4bN0 (n=1), 78.7% (68.6-85.8) in cT2N(+)(n=93), 68.0% (61.1-73.8) in cT3N(+)(n=218), 57.7% (51.7-63.2) in cT4aN(+)(n=301), and 25.0% (0.9-66.5) in cT4bN(+)(n=5). Conclusions: Both the survival and the proportion of overdiagnosis of stage I patients in patients with cT4aN0, categorized as cstage IIB, was almost same as in those cT3N(+) categorized as cstage III. In considering the candidate for further treatment development of NAC with high toxic regime in future, cT3N(+) and cT4aN0 should be considered as equivalent category.
A phase II study of paclitaxel and carboplatin plus PD-1 inhibitors combined with anlotinib as first-line treatment for advanced esophageal cancer.
Authors: Xu Mingfang , Pu Yu , Jiang Yuzhu , Liu Hong , Feng Yan , Qian Chengyuan , Dai Nan , Wang Dong , Li Mengxia
Published: January 2023

395

Background: The combination of anti-PD-1 mAb with chemotherapy is one of the standard first-line therapies for advanced esophageal cancer. Recent studies have shown that anti-PD-1 mAb combined with chemotherapy or targeted treatment can improve the efficacy of immunotherapy. The purpose of this study was to evaluate the efficacy and safety of paclitaxel and carboplatin (TC) combined with anlotinib, an anti-angiogenic TKI, and anti-PD-1 mAb, in the treatment of advanced esophageal cancer. Methods: This study was a parallel, single-center, open-label, phase II trial. A total of 90 patients (pts) with previously untreated, advanced or metastatic ESCC, with an age ranging from 18-75 years old, and an ECOG performance status ≤ 1 were planned to be enrolled into three arms with an allocation ratio of 1:1:1. Arm A received paclitaxel (175 mg/m2, IV, d1, q3w) /nab-paclitaxel (260mg/m2, IV, d1, q3w) + carboplatin (AUC 4-6, IV, d2, q3w) + anti-PD-1 mAb + anlotinib (8mg, PO, d1-14, q3w); Arm B received TC with anti-PD-1 mAb; Arm C received TC only. After 4-6 cycles of induction therapy, arm A and arm B would receive anti-PD-1 mAb plus anlotinib or anti-PD-1 mAb as maintenance therapy until disease progression or intolerable adverse events, respectively. The primary endpoint was ORR. Secondary endpoints included PFS, OS and safety. Results: At data cut-off date (Sep. 20, 2022), a total of 90 pts were enrolled and 88 pts were available for efficacy assessment. 25 of 28 pts achieved partial response (PR) in arm A, 13 of 30 pts PR in arm B, and 7 of 30 pts PR in arm C. The ORR (95% CI) were 89.3% (71.8-97.7) in arm A, 43.3% (25.5-62.6) in arm B, and 23.3% (9.9-42.3) in arm C. The DCR (95% CI) were 100% (87.7-100.0) in arm A, 96.7% (82.8-99.9) in arm B, and 83.3% (65.3-94.4) in arm C. The median PFS was not reached. The rate of treatment related adverse events (TRAEs) of any grade was 100% in all three groups, and grade 3 TRAEs were 23.3%, 16.7% and 13.3%, respectively. The most common grade 3 TRAEs were thrombocytopenia (6.7%), leukopenia (5.6%), neutropenia (5.6%). No grade 4 or 5 TRAEs occurred. Conclusions: The addition of anlotinib to immunotherapy plus chemotherapy as first-line therapy for ESCC demonstrated a high ORR (89.3%), and a manageable safety profile. Clinical trial information: NCT04471480 .
Endoscopic resection of gastrointestinal stromal tumor: The role of clip-and-cut endoscopic full-thickness resection.
Authors: Jung Hwoon-Yong
Published: January 2023

399

Background: To overcome the technical limitations of classic endoscopic resection for gastric gastrointestinal stromal tumors (GISTs), various methods have been developed. We analyzed the results of endoscopic submucosal dissection (ESD) and clip-and-cut endoscopic full-thickness resection (CASE), a modified full-thickness resection method for gastric GISTs to identify the role and its feasibility of CASE. Methods: The medical records of 83 patients diagnosed with GISTs after ER in 2005–2021 were retrospectively reviewed. ESD and CASE were performed in 51 and 32 patients. The clinical characteristics and outcomes were analyzed. Results: The GISTs were mainly found in the upper third of stomach for ESD (52.9%) and CASE (90.6%). In CASE group, there was a tendency that the most of GISTs were in deep muscularis propria or serosal layer (96.9%) compared to ESD group (45.1%). The R0 resection rates were 51.0% in ESD and 84.4% in CASE group, respectively. Perforation during procedure was frequently found in CASE group (25.5% vs. 68.8%), however only three patients were progressed to peritonitis. Seven cases (8.4%) required surgical treatment (6 ESD, 1 CASE) due to residual tumor (n=5), and post-procedure adverse events (n=2). No R0 or R1 resected cases experienced recurrence during the median 14-month follow-up except for one patient in ESD group. Conclusions: CASE showed higher R0 resection rate and was useful and safe in removing small gastric GISTs.
Phase II study of the combination of durvalumab, tremelimumab, and paclitaxel as second-line chemotherapy in biomarker-selected patients with metastatic gastric cancer.
Authors: Lee Keun-Wook , Kim Hark Kyun , Ryu Min-Hee , Zang Dae Young , Kim Ji-Won , Kim Bum Jun , Kim Hyung-Don , Kim Jin Won , Kang Yoon-Koo
Published: January 2023

401

Background: Currently, ramucirumab plus paclitaxel is the standard second-line chemotherapy in metastatic gastric cancer (mGC), however, its efficacy is very limited. MSI, PD-L1 (CD274), and EBV have been suggested as predictive biomarkers for immune checkpoint inhibitors in mGC. This study was conducted to evaluate efficacy and safety of the combination of durvalumab, tremelimumab, and paclitaxel as a second-line chemotherapy in mGC with potential biomarkers for immune checkpoint inhibitors. Methods: The combination of durvalumab, tremelimumab, and paclitaxel consisted of 1500 mg of i.v. durvalumab on day 1, every 4 weeks for 13 cycles, 75 mg of i.v. tremelimumab on day 1 every 4 weeks for 4 cycles, and 60 mg/m2 of i.v. paclitaxel on days 1, 8, and 15, every 4 weeks until disease progression or unacceptable toxicities. Patients (pts) with MSI-high mGC, EBV-positive mGC, or mGC with CD274 amplification, mutations of mismatch repair or POL gene, or tumor mutation burden (TMB) >5/Mb were included in second-line setting. Results: Forty-eight pts were enrolled. Overall response rate (ORR) was 52.1% with complete response in 4 (8.3%) pts, partial response in 21 (43.8%), stable disease in 14 (29.2%), and progressive disease in 8 (16.7%), and with response not evaluable in 1 (2.0%). With a median follow-up of 18.0 months (range, 7.1-39.4), the median progression-free survival (PFS) and overall survival (OS) were 5.3 months (95% CI, 3.7-6.9) and 13.1 months (95% CI, 5.2-21.0 ), respectively. Compared to mGC with other genetic alterations (n=25), mGC with TMB >20/Mb or MSI-high mGC (n=23) tended to have a higher ORR (56.5% vs 48%), and a prolonged PFS (median 7.2 vs 4.5 months; 44.0 vs 20.8% at 1 year). The combination chemotherapy was generally well tolerable; treatment-related grade 3 or 4 adverse events with frequency >5% included only neutropenia (10.4%) and anemia (8.3%), and there was no treatment-related death. Conclusions: The combination chemotherapy of durvalumab, tremelimumab, and paclitaxel showed encouraging efficacy, especially in mGC with TMB >20/Mb or MSI-high mGC, as a second-line chemotherapy with manageable toxicities in biomarker-selected mGC. Clinical trial information: NCT03751761 .
Outcomes of endoscopic resection for early gastric cancer in very elderly patients: A nationwide population-based study.
Authors: Kim Tae Jun , Lee Hyuk , Kim Jae J.
Published: January 2023

403

Background: Few studies have investigated the long-term outcomes of endoscopic resection for early gastric cancer (EGC) in very elderly patients. The aim of this study was to determine the appropriate treatment strategy and identify the risk factors for mortality in these patients. Methods: Patients with EGC who underwent endoscopic resection from 2006 to 2017 were identified using National Health Insurance Data and divided into three age groups: very elderly (≥85 years), elderly (65–84 years), and non-elderly (≤64 years). Their long- and short-term outcomes were compared in the three age groups, and the survival in the groups was compared with that in the control group, matched by age and gender. We also evaluated the risk factors for long- and short-term outcomes. Results: A total of 8,426 patients were included in our study: 118 very elderly, 4,583 elderly, and 3,725 non-elderly. The overall survival (OS) and cancer-specific survival (CSS) rates were significantly lower in the very elderly group than in the elderly and the non-elderly groups. Congestive heart failure was negatively associated with CSS. A significantly decreased risk for mortality was observed in all groups (P-value < 0.001). The very elderly group had significantly higher readmission and mortality rates within 3 months of endoscopic resection than the non-elderly and elderly groups. Further, cerebrovascular disease was associated with mortality within 3 months after endoscopic resection. Conclusions: Endoscopic resection for EGC can be helpful for very elderly patients, and it may play a role in achieving OS comparable to that of the control group.[Table: see text]
Clinical outcomes of endoscopic resection for gastrointestinal stromal tumor originating from the muscularis propria: A single-center experience.
Authors: Lee Moonwon , Kim Gwang Ha , Lee Bong Eun , Joo Dong Chan
Published: January 2023

407

Background: With the remarkable advance of endoscopic techniques, endoscopic submucosal dissection (ESD) has become an effective and safe treatment modality for various gastrointestinal tumors (GISTs). However, there is still a lack of evidence on endoscopic treatment of GISTs in the stomach. We aimed to investigate the efficacy and safety of ESD for gastric GISTs and to assess possible predictive factors for incomplete resection. Methods: Between October 2008 and July 2022, a total of 35 patients with gastric GIST underwent ESD at our hospital. Clinicopathologic characteristics of patients and GISTs, therapeutic outcomes, adverse events and follow-up outcomes were evaluated. Results: The overall rates of en bloc resection and complete resection were 77.1% (27/35), 68.6% (24/35), respectively. The median procedure time was 47.3 minutes (range, 15–131 minutes). The procedure-related bleeding and perforation rates were 2.9 % and 17.1%, respectively. In univariate analyses, EUS growth pattern (intraluminal growth, p = 0.027) was independently associated with complete resection. During the median follow-up period of 15.4 months (range, 5.7 – 129 months) in 35 patients except two patients who underwent surgery and one patient who failed to follow up, recurrence occurred in one patient with macroscopically incomplete resection. Conclusions: ESD is an effective, safe, and feasible treatment for gastric GISTs. The frequency of complete resection is increased in EUS with an intraluminal growth pattern. [Table: see text]
The optimal extent of lymph node dissection for gastric cancer with para-aortic lymph node metastases.
Authors: Wada Takeyuki , Yoshikawa Takaki , Ishizu Kenichi , Hayashi Tsutomu , Yamagata Yukinori
Published: January 2023

413

Background: Gastric cancer (GC) with para-aortic lymph node (PAN) metastasis is diagnosed as stage IV and basically treated with chemotherapy. Recently, D2 and PAN dissection after neoadjuvant chemotherapy (NAC) was reportedly effective when PAN metastasis was limited within #16a2/b1 area. However, PAN dissection is highly invasive surgical procedure and it still remains unclear whether PAN dissection contributes to the survival for these tumors. This study aimed to determine the optimal extent of lymph node dissection for these tumors focusing on survival benefit of PAN dissection. Methods: The study examined patients who received radical gastrectomy with D2 and PAN dissection after NAC for gastric cancer with PAN metastasis (#16a2/b1) from 2004 to 2015. Survival benefit of lymph node dissection was estimated using therapeutic value index (TI). TI was calculated by multiplication of incidence of metastasis and 5-year survival rate of patients with metastasis for each lymph node area. TI of D2 dissection area (TI-D2) and PAN area (TI-PAN) was calculated separately. Overall survival (OS) was calculated in patients who had metastasis to PAN pathologically after surgery (pPAN+ group) and those who had not (pPAN- group). The recurrence site was also examined. Results: Thirty-two patients were analyzed. TI-D2 and TI-PAN were 15.6 and 0.0, respectively. 5y-OS was 81.0% in pPAN- group (21 cases) but was 0.0% in pPAN+ group (11 cases). The most frequent recurrence site was the lymph nodes (82.4% of all recurrences). Among lymph node recurrence, almost all recurrence patterns included the PANs (85.7% of lymph node recurrence). Conclusions: The prognosis was extremely poor when tumor cells remained on PAN after NAC. In these cases, PAN recurrence was seen most frequently even after PANs had been dissected. Patients with PAN could have the chance for the cure only when tumor cells on PAN was completely eliminated by NAC. It is unclear whether they actually needed PAN dissection for pathologically negative PAN. The optimal extent of lymph node dissection after NAC might be D2 for GC with PAN metastasis.
First-line anti-EGFR or anti-VEGF therapy, tumour sidedness, and survival: Results from the South Australian (SA) Metastatic Colorectal Cancer (mCRC) Registry.
Authors: Krishnan Tharani , Ullah Shahid , Piantadosi Cynthia , Karapetis Christos Stelios , Townsend Amanda Rose , Roy Amitesh , Geerinckx Barbara , Maddern Guy , Roder David , Padbury Rob , Price Timothy
Published: January 2023

42

Background: The anti-EGFR monoclonal antibodies panitumumab (Pmab) and cetuximab (Cmab) and the anti-VEGF antibody bevacizumab (bev) have demonstrated clinical efficacy in mCRC in combination with first-line chemotherapy. Clinical and molecular characteristics, such as primary tumour sidedness, RAS, BRAF and MMR status are prognostic and predictive biomarkers for response to treatment. Our aim was to compare the survival and tumour characteristics of patients receiving first-line chemotherapy and antibody combinations using the SA mCRC Registry. Methods: This real-world registry has collected data from all patients diagnosed with mCRC in SA prospectively since 2006. We identified patients who had received first-line Pmab, Cmab or bev. Survival was analysed using the Kaplan-Meier method and log-rank test to compare outcomes based on primary tumour location. Results: Of the 5537 patients currently entered onto the registry, 1313 with RAS results available had received first-line anti-EGFR/VEGF antibodies and had colon tumour side recorded. The table summarises median overall survival (mOS) and patient characteristics. Survival was significantly shorter for those with right colon cancers (P < 0.001). There were more high-grade (P < 0.001), KRAS mutant (P = 0.004) and BRAF mutant (P = 0.036) tumours in those with right colon cancers, and a trend towards fewer curative liver resections (P = 0.059). There was no significant difference in mOS seen between Pmab, Cmab or bev for both left (P = 0.14) and right-sided (P = 0.88) primary tumours. Conclusions: There were more high-grade, BRAF and KRAS mutant patients with right colon tumours, and lower rates of liver resection, which may explain the significantly shorter mOS. The survival seen for Pmab and Cmab was almost identical for both right and left primary tumours. When comparing Pmab, Cmab and bev as first-line therapy, there was no significant difference in mOS for both left- and right-sided CRC. [Table: see text]
FGFR2-amplified gastroesophageal adenocarcinoma is a distinct genomic class: Lessons learned from a liquid biopsy platform.
Authors: Shariff Bushra , Barnett Reagan , Dayyani Farshid , Maron Steven Brad , Klempner Samuel J , Masannat Jude , Drusbosky Leylah , Mcgriskin Rory , Mehta Rutika
Published: January 2023

429

Background: Gastroesophageal cancers (GECs) are the 2nd highest cause of cancer mortality globally. Biomarkers such as MMR, PD-L1, and HER2 are critical for treatment strategies. Emerging biomarkers in late-stage clinical development include FGFR2b. Approximately 30% of GECs express FGFR2b, which is associated with a poor prognosis. FGFR2 amplification ( FGFR2amp) is seen in a subset of patients and may be particularly responsive to FGFR2-targeted approaches. We sought to elucidate the genomic landscape of FGFR2ampGECs using a ctDNA platform. Methods: We retrospectively queried the Guardant Health database from 2017-2022 for patients with advanced GECs who had ctDNA NGS (Guardant360, Redwood City, CA) performed as part of clinical care. Co-alterations were evaluated for patients who harbor FGFR2amp vs those without FGFR2amp detected via ctDNA. Fisher’s exact test was used for group comparisons. Results: Approximately 7100 patients met the diagnosis criteria. FGFR2amp was detected in 263 patients (3.7%). The majority were males (66 and median age in the cohort of FGFR2amp patients was 66 years (range 22-81 yrs). Most amps were high (+++) in gastric and GEJ (plasma CN≥4) and more frequently observed in patients who are tested at diagnosis (44%) vs progression (19%) (p=0.0147). The mean VAF across samples with high-level FGFR2amp is 22.42%. Patients with FGFR2amp were enriched for EGFR co-occuring amplifications and cell cycle pathway alterations. CDH1 was frequently mutated in pts under 50 who harbor FGFR2amp (p=0.0028). Thirty nine percent of patients with FGFR2amp were also found to harbor a gene fusion and 14% of patients with FGFR2amps harbored an activating fusion in FGFR1/2/3. Conclusions: FGFR2 is a validated target in GECs, and the contexture of FGFR2amp will be important to defining patient subgroups with responses to FGFR2-directed therapy. Here we define the FGFR2amp landscape which may help inform future combination strategies for this emerging biomarker.[Table: see text]
Assessment of complete pathologic response after neoadjuvant immunotherapy for MSI-H gastrointestinal cancers.
Authors: Vora Kruti Bhagirath , Ouyang Ben , Pappas Leon , Reynolds Kerry Lynn , Strickland Matthew , Allen Jill N. , Weekes Colin D. , Corcoran Ryan Bruce , Blaszkowsky Lawrence Scott , Ryan David P. , Franses Joseph Wang , Chakrabarti Sakti , Klempner Samuel J , Parikh Aparna Raj
Published: January 2023

43

Background: Immunotherapy (IO) has shown remarkable efficacy in gastrointestinal (GI) cancers with high microsatellite instability (MSI-H). We evaluated real world outcomes of patients treated with neoadjuvant IO for MSI-H colorectal (CRC) and gastroesophageal (GE) cancers. Methods: We queried diagnoses, pathology reports, and clinic notes of patients receiving IO at Massachusetts General Hospital from October 2014 to March 2022 using the Research Patient Data Registry and MATLAB. 1140 patients were identified with esophageal, gastric, colon, or rectal primaries. Of these, 56 were MSI-H and seven received neoadjuvant IO with curative intent. Results: Of the seven patients who received neoadjuvant IO for MSI-H CRC or GE cancers, three patients achieved complete pathologic response (pCR). Three patients had partial responses; one had a single residual lymph node tumor cell, one had residual T1b tumor and negative nodes, and one had residual T3 tumor and positive nodes. All patients with pCR had non-metastatic disease. Three of four patients with partial responses or progression had metastatic disease. Five patients had no recurrence by median follow-up of 10 months post-resection. One patient's cancer recurred 15 months post-resection, and one patient had progressive disease on neoadjuvant IO so did not undergo primary resection. Conclusions: Neoadjuvant IO shows promise for MSI-H GI cancers. Three of seven patients (43%) had pCR and three others (43%) had notable partial responses. There is a need to understand IO-refractory primary tumors and the differing effects of IO in local versus metastatic disease. While our data is limited by sample size, larger clinical trials can establish the safety and utility of neoadjuvant IO, potentially sparing many patients from surgery. We will collaborate with other centers for a larger scale analysis on neoadjuvant IO in MSI-H GI cancers. [Table: see text]