bluuebunny/crossref_metadata_2025 huggingface dataset:
The influence of procedural volume on the outcome of endoscopic submucosal dissection for gastric neoplasm: A nationwide population-based study.
Authors: Kim Jae Gyu , Park Jae Yong , Kim Beom Jin , Kim Mi-Sook
Published: January 2023

285

Background: Endoscopic submucosal dissection (ESD) is a well-established treatment modality for gastric neoplasms. The aim of this study was to investigate the effect of procedural volume on the outcome of endoscopic submucosal dissection (ESD) for gastric cancer or adenoma. Methods: Patients who underwent ESD for gastric cancer or adenoma from November 2011 to December 2017 were identified using the Korean National Health Insurance Service database. Operational definitions to identify target population and post-procedural complications were created by combining the diagnosis and procedure codes, and validated using individual hospital medical record data. The outcomes were the occurrence of post-procedural complications (bleeding, perforation, pneumonia, and 30-day mortality) and additional resection within 180 days after the initial ESD procedure. Hospital volume was categorized into four groups based on the mean annual number of procedures: very high-, high-, low-, very low-volume hospitals (VHVH, HVH, LVH, VLVH). The outcome of ESD was compared in relation to hospital volume. Results: There were 95,411 procedures in 89,780 patients during the study period. There were 5,607 composite events, which included 5,098 bleeding, 601 perforation, and 712 pneumonia cases, respectively. Additional resection within 180days occurred in 7,900 cases. There were significant differences in ESD-related adverse outcomes among the four hospital volume categories. Multiple logistic regression revealed that VHVH, HVH, and LVH were associated with significantly lower relative risk of composite outcome, when compared to VLVH. Similar tendencies were also shown in terms of bleeding, perforation, and pneumonia. This volume-outcome association was not evident in additional resection. Conclusions: Hospital volume was closely associated with adverse clinical outcome in patients with ESD for gastric cancer or adenoma. The outcomes of gastric ESD should be closely and systemically monitored to ensure the safety of patients. [Table: see text]
Survival benefit to immunotherapy according to site of organ involvement in metastatic anal cancer.
Authors: Peddireddy Arjun S , Johnson Benny , Wolff Robert A. , Huey Ryan , Holliday Emma , Das Prajnan , Skibber John Michael , Portier Shaelynn , Foo Wai Chin , Halperin Daniel M. , Morris Van K.
Published: January 2023

3

Background: For patients with metastatic anal cancer, demonstration of anti-tumor activity by anti-PD-(L)1 antibodies has expanded the treatment landscape. To date, there are no predictive biomarkers associated with clinical benefit to immunotherapy in this setting. In the absence of clinical trials directly comparing chemotherapy and immunotherapy for metastatic anal cancer, the optimal sequencing of therapeutic lines remains undefined because historical series have been limited to cytotoxic chemotherapy. We evaluated the survival outcomes of patients with metastatic anal cancer following treatment with immunotherapy and with chemotherapy. Methods: We reviewed retrospectively the MD Anderson Cancer Center database for patients with unresectable and/or metastatic anal cancer diagnosed between 6/2014 and 11/2021. Median survival was estimated using the Kaplan-Meier method and compared between subpopulations of interest with a log-rank test. Results: Among 82 patients with metastatic anal cancer, 68 (83%) were female, and the median age was 60 years (range, 39-81). With a median follow-up time of 24.6 months, the median lines of systemic therapy were 2 (range, 1-5). 58 (71%) received anti-PD-(L)1 immunotherapy, either alone (N=51) or in combination with bevacizumab or with MEDI-0457 on a clinical trial (N=7). Median progression-free survival times (PFS) for lines 1, 2, and 3 of systemic therapy were 7.2 months (95% CI (Confidence Interval) 5.3-9.1; N=82), 3.6 months (95% CI 2.4-4.8; N=58), and 4.1 months (95% CI 2.8-5.4; N=34), respectively. In the treatment-refractory setting, no difference in median PFS between chemotherapy and immunotherapy was observed (4.7 months vs 2.9 months, respectively; hazard ratio (HR) 0.9, 95% CI 0.5-1.4); p=.17). Median overall survival (OS) was estimated at 33.9 months (95% CI, 24.0-34.8). For patients with metastatic anal cancer treated with immunotherapy, involvement of only distant lymph nodes (N=10/58, 17%) was associated with improved median PFS (11.3 months vs 2.8 months; HR 3.5, 95% CI 1.8-6.6; p=.002) and median OS (45.2 months vs 27.1 months; HR 2.9, 95% CI 1.3-6.5, p=.02) than other sites of distant organ involvement (N=48/58, 83%). Conclusions: In this single-institution retrospective study at a large academic referral center, both chemotherapy and immune checkpoint blockade were effective treatment options for patients with metastatic anal cancer. These data provide historical context in estimating median PFS necessary for future trial design in patients with metastatic anal cancer. Lymph node-only distribution of distant metastatic disease was predictive for improved survival with immunotherapy. Pending further validation, these data provide novel identification of a potential predictive factor associated with benefit to immunotherapy in patients with metastatic anal cancer.
Pre-diagnostic delay among patients with curative esophageal and gastric cancer during the COVID-19 pandemic.
Authors: Wang Xin , Espin-Garcia Osvaldo , Bach Yvonne , Aoyama Hiroko , Ma Lucy Xiaolu , Barron Carly C. , Megid Thais Baccili Cury , Chen Eric Xueyu , Yeung Jonathan , Swallow Carol Jane , Brar Savtaj Singh , Wong Rebecca KS , Mesci Aruz , Kim John , Veit-Haibach Patrick , Kalimuthu Sangeetha , Jang Raymond Woo-Jun , Elimova Elena
Published: January 2023

302

Background: The majority of esophageal and gastric cancers are diagnosed at an advanced stage with poor overall survival (OS), leading some to propose screening, even in countries with a low incidence. Whether diagnostic delay from symptom onset has any impact on OS is unclear. We investigated this question in the peri-COVID19 pandemic era. Methods: We retrospectively analyzed a cohort of 308 patients with esophageal, gastroesophageal junction, or gastric carcinoma treated with curative intent at the Princess Margaret Cancer Centre from January 2017 to December 2021. Clinical details pertaining to the initial presentation were determined through a retrospective chart review. OS was estimated using the Kaplan-Meier method. Cox proportional hazards regression models were used to assess the association between pre-diagnostic interval with OS adjusting for baseline patient characteristics. Results: The median interval from symptom onset to diagnosis was 98 days (IQR 47-169 days). Using a cox proportional hazard model, prolonged pre-diagnostic interval was not associated with worse OS (HR 1.00, P=0.62). Comparing patients diagnosed before and during the COVID19 pandemic, there was a notable increase in diagnostic delay with median pre-diagnostic interval increasing from 92 to 126 days (P=0.007). Median age at time of diagnosis was 69.6 during the pandemic vs 64.7 before the pandemic. Linear regression showed squamous cell histology was significantly associated with increasing time to initial diagnosis (P=0.04). Looking at other delay metrics, there were no changes in time interval from diagnosis to treatment during versus before the pandemic (median = 1.7 weeks for both), and there was no change in time from diagnosis to resection in those patients who underwent surgery. Conclusions: The COVID19 pandemic caused significant diagnostic delay for patients presenting with curative esophageal and gastric cancer. We found no evidence of pandemic-related health system delays in treatment, once a diagnosis was made. The lack of correlation of pre-diagnostic interval with OS may reflect underlying tumour biology as the driving force that determines prognosis.
Long-term outcomes after laparoscopy-assisted total or proximal gastrectomy with nodal dissection for clinical stage I gastric cancer: Japan Clinical Oncology Group study (JCOG1401).
Authors: Sakuramoto Shinichi , Katai Hitoshi , Katayama Hiroshi , Iwamoto Shintaro , Hasegawa Yasuhiro , Nomura Takashi , Makino Shigeto , Watanabe Masaya , Omori Takeshi , Yoshikawa Takaki , Ojima Toshiyasu , Terashima Masanori
Published: January 2023

305

Background: JCOG0912 supports the non-inferiority of laparoscopy-assisted distal gastrectomy (LADG) compared with open distal gastrectomy (ODG) for clinical stage I gastric cancer relapse-free survival (RFS), suggesting that LADG should be considered a standard treatment option when performed by experienced surgeons. No prospective study evaluating laparoscopy-assisted total gastrectomy (LATG) and laparoscopy-assisted proximal gastrectomy (LAPG) has been completed in terms of both safety and long-term survival. Considering that the results of the phase III trial to evaluate the long-term outcome of LADG (JCOG0912) could guarantee that of LATG/LAPG, we conducted a single-arm confirmatory trial (JCOG1401) to evaluate the safety of LATG/LAPG for clinical stage I proximal gastric cancer and JCOG1401 confirmed the safety of LATG/LAPG. Long-term outcomes as the secondary endpoints of this study are reported here after 5-year follow-up period. Methods: Laparoscopic operators were limited to credentialed surgeons. The extent of nodal dissection was selected based on the Gastric Cancer Treatment Guidelines in Japan. The primary endpoint was the proportion of grade 2 (CTCAE ver. 4.0) or greater esophageal anastomotic leak. The sample size was determined to be 245 considering a threshold of 8% and expected value of 3% with a one-sided alpha error of 2.5% and statistical power of 90%. The secondary endpoints were overall survival (OS) and RFS. Results: Between April 2015 and February 2017, 245 patients were enrolled. Among them, 1 patient was excluded from safety analysis due to ineligible. LATG/LAPG was performed in 195/49. 170/47/17/8/2 patients had pStage IA/IB/II/IIIA/IIIB disease and 190/31/15/8 patients had pT1/T2/T3/T4 disease, respectively. Grade 2 or greater esophageal anastomotic leak was 2.5% (6/244) (95% CI 0.9-5.3), as previously reported. 5-year OS was 91.2% (95% CI 86.9-94.2). 5-year RFS was 90.0% (95% CI 85.5-93.2). Among 22 deaths, 14 patients died without recurrence and 8 patients died with recurrence. Twelve recurrences were observed in 5/2/4/1 patients for pT1/T2/T3/T4. The sites of recurrence were peritoneal metastasis in 2 cases, hematogenous metastasis in 9 cases (liver: 6, bone: 2, lung: 1), and other in 1 case. Conclusions: The long-term outcomes of LATG/LAPG for Stage I gastric cancer patients were excellent and seem comparable to those of open procedures. Similar to JCOG0912, JCOG1401 guarantee the long-term survival of LATG/LAPG. Clinical trial information: UMIN000017155 .
Long-term quality of life in patients with metastatic esophagogastric cancer receiving first-line systemic therapy.
Authors: Pape Marieke , Vissers Pauline A.J. , Slingerland Marije , Haj Mohammad Nadia , van de Poll-Franse Lonneke , Verhoeven Rob , Van Laarhoven Hanneke W.M.
Published: January 2023

306

Background: Thus far, evidence that quality of life (QoL) remains stable during 1st line systemic therapy of patients with metastatic esophagogastric cancer (mEGC) originates from randomized clinical trials (RCTs). Outcomes from a population-based study provides inside into the effect of systemic therapy on HRQoL in daily clinical practice. The aim of this study was to assess QoL of patients with mEGC at baseline, during 1st line, at progression and after disease progression. Methods: Patients diagnosed with mEGC (2014-2020) receiving 1st line systemic therapy registered in the Prospective Observational Cohort study of Oesophageal-gastric cancer Patients (POCOP) were included. QoL was measured with the EORTC QLQ-C30 and -OG25 at baseline, during 1st line therapy, at progression and after disease progression. Results: Of the 263 included patients, 123, questionnaires were available at baseline, 161 during 1st line, 77 at progression and 89 after progression. Results of the mixed effect models showed that global health status and four functioning scales deteriorated after progression as compared to baseline. Largest improvements during 1st line treatment were observed for odynophagia (mean change -17.3), anxiety (-14.9), dysphagia (-11.7) and eating restrictions (-11.1). Trouble with taste deteriorated at all three time points. Conclusions: In accordance to RCTs, QoL outcomes remained relatively stable or improved during 1st line therapy in patients with esophagogastric cancer. Deterioration of functioning scales were mainly observed after progression. [Table: see text]
Role of chemotherapy in clinical T2N0M0 gastric cancer.
Authors: Bawek Sawyer , Vedire Yeshwanth , Groman Adrienne , Mukherjee Sarbajit
Published: January 2023

308

Background: The role of chemotherapy for patients with early stage, node-negative gastric adenocarcinoma (T2N0M0) remains unclear. Possible options are surgery alone, surgery followed by adjuvant chemotherapy, or perioperative chemotherapy. The objective of our study was to investigate the role and sequence of chemotherapy in T2N0M0 gastric adenocarcinoma. Methods: The National Cancer Data Base (2006-2017) was used to identify patients with T2N0M0 gastric adenocarcinoma. Patients were categorized into 3 groups, surgery alone (S), surgery followed by adjuvant chemotherapy (AC), and peri-operative chemotherapy (POC). Univariate and multivariable Cox proportional-hazards models were performed to evaluate treatment differences in overall survival (OS). Patients were further sub-categorized into two subgroups based on the number of regional nodes examined, less than 15 (RNE<15) and greater or equal to 15 (RNE>15). Univariate and multivariable Cox proportional-hazards models were performed on each subgroup to assess the treatment differences within two groups. Results: The retrospective study analyzed 3,142 patients between 2006 to 2017. Surgery alone represented 2,090 patients (66.5%), AC group had 360 patients (11.5%), and the POC group 692 patients (22.0%). The median age of the population was 70 yrs. Mean inpatient stay was 12.5 days in S, 9.2 days in AC and 10.1 days in the POC group (p<0.001). In the multivariable model, surgery followed by adjuvant chemotherapy (HR 0.75, p=0.003), RNE>15 (HR 0.73, p<0.001), patients treated at academic facilities (HR 0.84, p=0.005), female sex (HR 0.84, p=0.004), and Asian race (HR 0.69, p=0.002) had better outcomes. There were 1,526 (49.2%) patients with RNE<15 and 1,577 (50.8%) patients with RNE>15. Subgroup analysis showed that peri-operative chemotherapy for RNE<15 was beneficial (HR 0.74, p= 0.029). Patients with RNE>15 had an improved survival with surgery followed by adjuvant chemotherapy (HR 0.72, p= 0.017) in the multivariable model. Conclusions: Surgery followed by adjuvant chemotherapy was found to be beneficial in patients having a T2N0M0 Gastric Cancer. However, the number of lymph nodes examined during surgery influences this association. Perioperative chemotherapy maybe beneficial for patients who were under staged due to inadequate exploration of lymph nodes during surgery.
Chemotherapy-induced neuropathy in esophagogastric cancer.
Authors: van Velzen Merel , Pape Marieke , van Kleef Jessy Joy , Slingerland Marije , Beerepoot Laurens V. , Mostert Bianca , Haj Mohammad Nadia , Van Laarhoven Hanneke W.M.
Published: January 2023

309

Background: Treatment of locally advanced and metastatic esophagogastric cancer (EGC) largely depends on systemic treatment including taxanes or platinum compounds – agents which are known to cause chemotherapy induced peripheral neuropathy (CIPN). To date, the extend of CIPN in EGC has not been investigated in real-world data. Methods: We identified patients with EGC from the Netherlands Cancer Registry (NCR) and Prospective Observational Cohort study of Oesophageal-gastric cancer Patients (POCOP) who underwent systemic treatment between 2016 and 2018 and completed at least one EORTC QLQ-CIPN20 questionnaire. Total CIPN scores and scores for the motor, sensory and autonomic scales (ranged 0-100) were calculated, and analyzed over time for patients receiving chemoradiation (CRT), peri-operative chemotherapy (POC) and patients primarily treated with palliative chemotherapy (PC). To gain insight in the differences between CIPN score at baseline and after 3, 6, 9, 12, 18 and 24 months we constructed linear mixed effect models. Results: We included 1052 EGC patients. 769 patients received CRT (response: 76% at baseline, 30% after 24 months), 143 received POC (response: 79% at baseline, 33% after 24 months) and 140 received PC (response: 74% at baseline, 28% after 12 months). Over time, neuropathy scores increased in all scales for patients receiving POC and PC, with a maximum increase of 16.5 points in total CIPN score after 6 months in the PC group compared to baseline. For patients receiving CRT, increase in neuropathy scores was more subtle, with a maximum increase in total CIPN score of 4.3 points after 24 months compared to baseline. Results of mixed effect models showed a significant increase of CIPN scores over time in all three groups compared to baseline, persisting for as long as two years after start of initial treatment. Conclusions: CIPN frequently occurs in EGC patients treated with chemotherapy, especially with PC. Due to the possible irreversibility of CIPN, it is important that clinicians inquire patients about neurotoxicity often, adjust the dose of neurotoxic agents as needed and that more research is done into strategies possibly preventing the occurrence of CIPN. Results of mixed model analysis to assess changes in total CIPN score over time. Each model was adjusted for age, sex, performance status and number of comorbidities. The model for POC and PC was also adjusted for use of oxaliplatin.[Table: see text] *p-value <0.001 aChemoradiotherapy bPeri-operative chemotherapy cPalliative chemotherapy, no estimates were calculated for 18 and 24 months due to the low number of responses.
Anlotinib plus PD-1 inhibitors as chemo-free therapy in advanced or metastatic esophageal cancer: Updated results from a retrospective real-world study.
Authors: Hong Yonggui , Wu Tao , Lu Ping , Chang Zhiwei , Liang Wei , Zhang Guifang , Tian Yongjing , Wang Junsheng
Published: January 2023

310

Background: Compared to standard chemotherapy, immune checkpoint inhibitors monotherapy and combined with chemotherapy regimens have been shown significant benefits for patients with advanced or metastatic esophageal cancer in both second-line and first-line treatment, respectively. Anlotinib was an effective second-line monotherapy for esophageal squamous cell carcinoma in China and the combination of anlotinib and immunotherapy might be a promising strategy. The study aimed to investigate the efficacy and safety of anlotinib plus PD-1 inhibitors during the treatment of esophageal cancer in the real world setting. Methods: This is a multicenter real-world study in patients with unresectable locally advanced, recurrent or metastatic esophageal cancer, who would benefit from anlotinib plus a PD-1 inhibitor under the doctor's evaluation. The enrolled patients received treatment according to physicians. The primary endpoint was PFS, and secondary endpoints included ORR, DCR and OS. The response to treatment was evaluated according to RECIST version 1.1. In addition, adverse events were evaluated by CTCAE v5.0. Results: Between May 2020 and Sep 2022, 207 pts were enrolled. 109 comprised the evaluable population. In the full analysis set, 203 patients were squamous cell and 4 were adenocarcinoma histology. 137 of 207 (66.2%) pts were male. 44(21.3%) had an ECOG performance status of 0, 136 (65.7%) status of 1 and 27 (13.0%) status of ≥2. 47 pts had previously used anti-PD-1/PD-L1 antibody or vascular targeting drugs, of which 8 cases had combined anti-PD-1/PD-L1 antibody and vascular targeting drugs. Among the 109 evaluable pts, 17 (15.6%) pts received first-line therapy, 64 (58.7%) second-line and 28(25.7%) third & above line. Of which, 5 patients achieved complete response (CR), 32 pts partial response (PR), 62 pts stable disease (SD), illustrating an ORR of 34.0% (95%CI 25.1-43.6) and a DCR of 90.8%(95%CI 83.8-95.5). In the first line therapy, ORR was 47.1% and DCR was 88.2%. In the second line therapy, ORR was 32.8% and DCR was 96.9%. In the third & above line, ORR with 28.6% and DCR with 78.6% were observed. Median PFS was not reached, 6m-PFS rate was 87.9%. Treatment related adverse events (TRAEs) were reported in 55 pts (50.5%). 6 patients had grade 3 or more TRAEs. Conclusions: Anlotinib plus PD-1 inhibitors for advanced or metastatic esophageal cancer demonstrated a promising clinical benefit and a manageable safety profile. Further investigation in larger cohorts and even randomized controlled studies is warranted. Clinical trial information: NCT04966611 .
Symptom burden and functioning status in patients with advanced upper gastrointestinal cancers.
Authors: Wang Xin Shelley , Hess Lisa M. , Shen Shu-En , Gonzalez Elizabeth , Jomaa Mona K , Liepa Astra M.
Published: January 2023

311

Background: Providing accurate symptom profiles is essential to facilitate integration of patient-reported outcome measures (PROs) into routine oncologic care. This study described the symptom trajectories and functioning status in patients with advanced esophageal, gastroesophageal junction (GEJ), or gastric cancers. Methods: The study included adult patients with advanced upper gastrointestinal (UGI) cancers who were initiating a new line of therapy at time of enrollment. Multiple symptoms were assessed weekly for 12 weeks, then every two weeks until Week 36 using the electronically administered M.D. Anderson Symptom Inventory GI module (MDASI-GI). Patients also completed the EORTC QLQ-C30 every six weeks. Longitudinal PRO data were analyzed using mixed-effect models. Time to deterioration was estimated using Kaplan-Meier method. Multivariable regression models evaluated the association of PROs with tumor response. Patients were classified in a high symptom burden group if their MDASI-GI symptoms were scored > 4 (scale of 0-10) for trajectory analysis. Results: Of the 111 enrolled patients, primary tumor site was available for 108 patients: esophageal (33%), GEJ (26%), gastric (41%). The mean age was 60.2 years; 70% were male. Nineteen patients who dropped within one week after baseline reported more severe vomiting and inability to eat than those who provided more post-baseline data (n=92). For the 92 patients, the top 6 most severe items at baseline were fatigue, lack of appetite, disturbed sleep, pain, drowsiness, and inability to eat. At baseline, patients who were treatment-naïve (n=43) reported more severe symptom burden and financial difficulty than patients who had received prior therapy (n=49). Those who were treatment-naïve reported faster general activity deterioration during the first 12 weeks than those who had received prior treatment (hazard ratio=2.183, 95% CI: 1.018, 4.673). More severe shortness of breath at baseline was significantly associated with better tumor response by Week 12 (odds ratio=1.35, 95% CI: 1.05, 1.74) for all patients with tumor response data. Trajectory analysis showed high symptom burden for pain (35% of patients), fatigue (60%), disturbed sleep (32%), lack of appetite (60%), drowsiness (54%), difficulty swallowing (37%), and inability to eat (50%) during the initial 12 weeks. High symptom burden continued for pain (41% of patients), fatigue (55%), lack of appetite (59%), drowsiness (48%), and numbness (29%) for Weeks 12-36. Conclusions: This longitudinal study documented high prevalence of disease- and treatment-related symptom burden and functioning deterioration among patients with advanced UGI cancers. These data support the implementation of PRO assessment in the routine patient care of this cohort of patients with significant physical and psychosocial challenges.
Tumor mutational burden as a potential predictive marker for the efficacy of immunotherapy in advanced gastric cancer.
Authors: Jang Jae Yeon , Jeong Sun Young , Kim Seung Tae
Published: January 2023

324

Background: Tumor mutational burden (TMB) is known as an independent predictive factor in predicting treatment response of immunotherapy. We aimed to evaluate the efficacy of immunotherapy in advanced gastric cancer (AGC) according to TMB and other markers. Methods: The patients with AGC, aged ≥ 18, who received pembrolizumab or nivolumab from October 1, 2020, to July 27, 2021, at Samsung medical center in Korea, were analyzed retrospectively. TMB was measured by next-generation sequencing-based assays, and PD-L1 is tested using immunohistochemical assay 22C3 pharmDx. Referring to the results of previous studies, TMB-high was defined as 14.31 mutations/megabase (mt/Mb) or above. Results: A total of 54 AGC patients who were treated with immunotherapy, pembrolizumab or nivolumab, were analyzed. Seven patients were TMB-high, and 47 patients were TMB-low. Compared to TMB-low group, TMB-high group showed higher overall response rate (ORR) (42.9% vs 6.4%, p=0.023), and disease control rate (66.7% vs. 22.9%; p=0.033). The median OS was longer in the TMB-high group with 22.4 months (95% CI, 19.738-25.115), while the TMB-low group with 3.6 months (95% CI, 2.109-5.104; p=0.020). In addition to TMB, microsatellite status was statistically significantly associated with the efficacy of immunotherapy in AGC. Microsatellite instability group had better ORR (n=3/4, 75%) compared to microsatellite stable group (n=4/50, 8.0%; p=0.005). Other than that, the ORR of the patients whose PD-L1 CPS was 1 or above did not differ from the patients whose PD-L1 CPS was lower than 1. Although there was no statistical significance, among TMB-low patients, PD-L1 CPS ≥1 group numerically exhibited a higher overall response rate (13.0% vs 4.0%; p=0.338). Conclusions: In our analysis, the cut-off value of TMB was set to 14.31mb/Mt, and TMB-high was associated with the better ORR and OS of immunotherapy in AGC. TMB could be a potential predicting marker for a therapeutic response of immunotherapy in AGC.[Table: see text]
Exploring real-world outcomes with nivolumab plus chemotherapy in patients with advanced gastroesophageal adenocarcinoma.
Authors: Chen Clara , Zhang Ying , You Min , Theodorou Eleni , Bertwistle David
Published: January 2023

325

Background: In the pivotal CheckMate-649 trial, nivolumab in combination with chemotherapy (nivo + chemo), compared with chemotherapy alone (chemo), demonstrated superior efficacy in patients with previously untreated, advanced gastric, gastro-esophageal junction, or esophageal adenocarcinoma (collectively: gastroesophageal adenocarcinoma). This study aimed to describe the real-world patterns of use and effectiveness of nivo + chemo for first-line (1L) treatment of advanced gastroesophageal adenocarcinoma. Methods: Patients aged ≥18 years, newly diagnosed with unresectable, advanced or metastatic, HER2-negative gastroesophageal adenocarcinoma, who received nivo + chemo or chemo only between 4/1/2021 and 5/31/2022 were identified from the Flatiron Health database. Chemo regimens included FOLFOX or CAPEOX. Patients were followed from index date (start of 1L therapy) until death, loss of data availability, or end of data abstraction (05/31/2022), whichever occurred first. Results: 352 patients with advanced or metastatic gastroesophageal adenocarcinoma were eligible for the analysis (N=158 in the nivo + chemo group and N=194 in the chemo group). Baseline demographic and clinical characteristics were balanced between groups. Median follow-up was 3.6 (interquartile range [IRQ]: 1.5–8.1) months for nivo + chemo and 4.4 (IQR: 1.9–7.6) months for chemo. 44.3% of patients in the nivo + chemo group and 36.1% in the chemo group had <3 months of follow-up available. Median overall survival (OS) from index date was not reached (95% confidence interval [CI]: 9.0 months, –) in the nivo + chemo group and was 10.0 (95% CI: 8.5, 11.6) months in the chemo group. 43 patients (27.2%) in the nivo + chemo group died during the study period compared with 64 patients (33.0%) in the chemo group. Median progression-free survival (PFS) from index date in patients who received nivo + chemo was 6.9 (95% CI: 5.6, 8.2) months compared to 5.5 (95% CI: 4.8, 7.4) months in patients who received chemo. Similar trends were observed in the subgroup of patients with a PD L1 combined positive score (CPS) ≥1, while data on the CPS ≥5 subgroup were not mature enough for meaningful analyses. Conclusions: The addition of nivolumab to chemotherapy for 1L treatment of advanced or metastatic gastroesophageal adenocarcinoma showed a trend towards survival benefit in the real-world setting. The study is ongoing. Subsequent analyses will capture a larger patient sample and longer follow-up, and describe PD L1 CPS-based subgroups. [Table: see text]
Impact of obesity on postoperative outcomes in patients undergoing esophagectomy for resectable esophageal cancer.
Authors: Patel Nikhil , Patel Pranav , Doyle Joseph , Geropoulos Georgios , Bhogal Ricky Harminder , Allum William H. , Chaudry M. Asif , Kumar Sacheen
Published: January 2023

327

Background: The prevalence of obesity (Body Mass Index>30kg/m^2) is rising in the western world and is a risk factor for gastrointestinal malignancy. It is considered a risk factor for poor surgical outcomes including impaired wound healing and venous thromboembolism. Dysphagia is a late sign of esophageal cancer and is associated with pre-operative malnutrition and weight loss. However, the true impact of obesity on outcomes after esophagectomy is controversial. This analysis investigates the impact of pre-operative obesity on outcomes following esophagectomy for esophageal cancer. Methods: All patients with recorded pre-treatment BMI, who underwent surgery from January 2005 to June 2022 at a single tertiary, specialist cancer centre in the United Kingdom (UK), were included in this study. Demographic details including BMI and tumour staging (TNM classification) were collected, as well as total length of inpatient and critical care admission (LOS), 30- and 90- day mortality. Statistical analyses were performed on the R platform. Results: A total of 401 patients (348 male, 53 female) underwent resectional surgery for esophageal cancer; 132 (32.9%) were of normal BMI (18.5-24.9kg/m^2), 162 (40.1%) were overweight (BMI of 25-29.9kg/m^2), and 108 (26.9%) were obese (BMI>30kg/m^2). The mean BMI for obese patients was 33.6kg/m^2 and mean age was 62.5 years in this cohort. Laparoscopic Ivor-Lewis esophagectomy was the commonest procedure performed on obese patients (57/108, 52.3%). When all patients were categorised into healthy BMI, overweight or obese cohorts, there was no statistically significant difference in post-operative complications at Clavien-Dindo grade II or lower, (p=0.500) or grade IIIa or higher (p=0.201). Furthermore, there was no statistically significant difference in total inpatient LOS (p=0.503), length of critical care admission (p=0.358), 30-day (p=0.836) or 90-day mortality (p=0.691). Conclusions: Obesity is not significantly associated with increased risk of postoperative complications, LOS, 30- or 90-day mortality in patients undergoing esophagectomy for cancer. The increasing uptake of minimally invasive surgery for esophageal cancer resections may also be associated with favourable surgical outcomes being achieved in patients with BMI>30kg/m^2.
Prediction of risk factors associated with readmission after robotic esophagectomy.
Authors: Meredith Kenneth Lee , LeBlanc Gabrielle , Takahashi Caitlin , Huston Jamie , Shridhar Ravi
Published: January 2023

328

Background: Approximately, 20,640 new esophageal cancers (EC) will be diagnosed in 2022 and this will result in 16,410 deaths. Surgical resection remains the only potentially curative option, however significant morbidity and mortality ensues. Robotic approaches to esophageal resection have decreased overall length of hospitalizations. However, readmissions rates continue to be a significant concern. We sought to evaluate factors predicting readmission after robotic assisted trans-thoracic esophagectomy (RATE). Methods: Utilizing a prospectively maintained esophageal database, we identified patients with EC who underwent RATE between 2009-2022. We then stratified by readmissions, length of hospitalization and post-operative complications. Pre-operative, peri-operative and post-operative risk factors were identified as predictors of readmissions. Baseline univariate comparisons were made for continuous variables using both the Mann-Whitney U and Kruskal Wallis tests. Pearson’s Chi-square test was used to compare categorical variables. Multivariate analysis was performed identifying predictors of readmission. Results: We identified 312 patients, who underwent RATE with a median age of 68 (38-91). There were 29 (9.3%) patients who underwent readmission. There were no differences in age (p=0.10), gender (p=0.39) BMI (p=0.22), or histology (p=0.35) between patients that were readmitted and those that were not. ASA scores were higher in those that were readmitted p=0.01 compared to those who were not. The median length of hospitalization (LOH) was 8 (7-11) and did not differ between those that were re-admitted and those that were not p=0.79. The most common reasons for re-admissions were pulmonary 16 (5.1%), anastomotic leak 6 (1.9%), soft tissue infection 2 (0.6%), nutrition 3 (1%) and gastrointestinal 2 (0.6%). Pre-operative risk factors predictive of readmissions included cardiac disease p=0.002 and diabetes p=0.04. Operative risk factors: estimated blood loss p=0.9 and operative time p=0.24 did not predict readmission. Post-operative complications occurred in 93 (29.8%) of patients. Any post-operative complication p=0.32 did not predict re-admission with the exception of anastomotic leak p=0.04. Additionally, length of ICU did not differ between those re-admitted and those who were not, p=0.96. Ninety-day mortality was significantly higher in those that were re-admitted, 13.8% vs 4% in those that were not re-admitted, p=0.001. Multivariate analysis revealed that cardiac disease, diabetes, ASA score, and anastomotic leak were all predictors of readmission. Conclusions: Readmission after RATE remains low despite decreased LOH. Patients that are readmitted will have a significantly higher risk of mortality at 90-days. Pre-operative, peri-operative and post-operative factors can be used to accurately predict risk for readmission after robotic esophagectomy.
Randomized, global, phase 3 study of tislelizumab (TIS) + chemotherapy (chemo) versus placebo (PBO) + chemo as first-line (1L) treatment for advanced or metastatic esophageal squamous cell carcinoma (ESCC) (RATIONALE-306): Non-Asia subgroup.
Authors: Raymond Eric , Hubner Richard , Gotovkin Evgeny , Wyrwicz Lucjan , Van Cutsem Eric , Jimenez-Fonseca Paula , Pazo-Cid Roberto , Xu Jianming , Kato Ken , Tao Aiyang , Wang Lei , Peng Yanyan , Li Liyun , Yoon Harry H.
Published: January 2023

340

Background: TIS, an anti-programmed cell death protein 1 (PD-1) antibody, + chemo as 1L therapy demonstrated statistically significant and clinically meaningful improvement in overall survival (OS) vs PBO + chemo in patients with advanced or metastatic ESCC (hazard ratio [HR] 0.66 [95% confidence interval (CI) 0.54, 0.80]; P< 0.0001), with a manageable safety profile, at interim analysis of the phase 3, double-blind RATIONALE-306 study (NCT03783442). Here, we report data from the non-Asia subgroup (Europe, Northern America, and Oceania). Methods: Adults with advanced or metastatic ESCC, with no prior systemic treatment for advanced disease were randomized 1:1, (stratified by region, prior definitive therapy, and investigator [INV]-chosen chemo) to receive TIS 200 mg intravenously (IV) once every 3 weeks (Q3W) (Arm A) or PBO IV Q3W (Arm B), with platinum + fluoropyrimidine, or platinum + paclitaxel until disease progression by INV per RECIST v1.1, intolerable toxicity, or withdrawal. The primary endpoint was OS in the intent-to-treat population. Secondary endpoints included: progression-free survival (PFS), objective response rate (ORR), and duration of response (DoR) by INV per RECIST v1.1; OS in the programmed death-ligand 1 score ≥10%; and safety. Results: Of 649 randomized patients, 163 (25.1%) were from the non-Asia subgroup (Arm A, n = 83; Arm B, n = 80). At data cutoff (Feb 28, 2022), the median study follow-up time in the non-Asia subgroup was 16.0 months (mo) in Arm A vs 8.4 mo in Arm B. OS (median 16.3 vs 9.0 mo; unstratified HR 0.66 [95% CI 0.45, 0.96]) and PFS (median 7.7 vs 5.5 mo; unstratified HR 0.59 [95% CI 0.41, 0.83]) were improved in Arm A vs Arm B, respectively. Arm A had higher ORR (61.4% vs 41.3%, odds ratio 2.27 [95% CI 1.21, 4.25]) and longer median DoR (7.1 mo [95% CI 5.6, 9.6] vs 5.7 mo [95% CI 3.8, 8.3]) than Arm B. More patients in Arm A vs Arm B experienced ≥1 treatment-related adverse event (TRAE; 94.0% vs 88.5%), serious TRAEs (25.3% vs 17.9%), and discontinuation due to treatment-emergent AEs (42.2% vs 35.9%, respectively). Similar proportions of patients in Arm A vs Arm B had ≥grade 3 TRAEs (56.6% vs 52.6%), and TRAEs leading to death (1.2% vs 1.3%), respectively. Conclusions: In the non-Asia subgroup, 1L TIS + chemo showed a clinically meaningful improvement in OS vs PBO + chemo in patients with advanced or metastatic ESCC, with a manageable safety profile, consistent with published results in the overall population. Clinical trial information: NCT03783442 .
Two cycles versus four cycles of neoadjuvant camrelizumab plus chemotherapy in patients with locally advanced esophageal squamous cell carcinoma (ESCC): A prospective, multicenter and randomized study.
Authors: Zhang Qin , Cao Guochun , Fan Zhaohui
Published: January 2023

350

Background: Increasing evidences support the effects of neoadjuvant immune checkpoint inhibitors plus chemotherapy in locally advanced ESCC. However, the period of neoadjuvant is yet to be completely elucidated. This study was designed to compared the efficacy and safety of two cycles with four cycles of neoadjuvant camrelizumab plus chemotherapy in ESCC. Methods: Patients (pts) aged 18 to 75, with pathological confirmed and resectable ESCC were eligible. Enrolled pts were randomly assigned to two or four cycles of neoadjuvant with intravenous camrelizumab (200 mg, day 1) plus albumin-bound paclitaxel (175mg/m2, day 1) and carboplatin (area under curve 5, day 2) of 21-day cycle. The primary endpoint was pathologic complete response (pCR) rate. Secondary endpoints included the R0 resection rate, objective response rate (ORR), disease control rate (DCR) and adverse events (AEs). ChiCTR2100051154. Results: From 1/2022 to 8/2022, 41 pts were enrolled randomized (21 in the two-cycle and 20 in the four-cycle group). There were 15 (71.4%, 15/21) and 6 (30.0%, 6/20) pts underwent surgery. Compared with (46.7%, 7/15) in two-cycle group, we observed a higher pCR rate (50.0%, 3/6) in four-cycle group. The ORR achieved 60% (two-cycle group) and 66.7% (four-cycle group) respectively. DCR and R0 resection rate achieved 100% in both groups. Pts were well-tolerated in both groups, and 4.8% (1/21) and 5.0% (1/20) pts experienced grade 3/4 AEs. Conclusions: It is the first study to compare the periods of immuno-chemotherapy in the neoadjuvant setting for ESCC. Four cycles neoadjuvant achieved a numerically higher pCR rate and ORR compared with two cycles. Moreover, pts in 4-cycle group did not experienced more frequent or serious AEs. Clinical trial information: ChiCTR2100051154 .
Effect of robot-assisted gastric ESD in difficult ESD locations.
Authors: Kim Sang Hyun , Keum Bora , Choi Hyuk Soon , Jeen Yoon Tae , Chun Hoon Jai
Published: January 2023

355

Background: Since its introduction, endoscopic submucosal dissection (ESD) has become a standard treatment for early malignant lesions of stomach. However, ESD is technically demanding and it bears a high risk of complication for beginners. The difficulty of the ESD technique tends to depend on the location of the lesion. We compared and analyzed the efficacy of the ESD assistive robot that we developed in the location where stomach ESD is considered difficult. Methods: We have developed an automated simulator that can implement gastric ESD locations. An EndoGel (Sunarrow, Tokyo, Japan) was attached to the simulator to implement a virtual gastric location where ESD is difficult. "Difficult ESD locations" were selected in consideration of the location where a lot of muscle damage and frequent blind dissections occurred when conventional ESD was performed. An experienced endoscopist performed ten robot-assisted ESDs or conventional ESDs in 3 difficult and 3 easy positions, respectively. Results: While there was no significant difference in dissection speed of robot ESD and conventional ESD in easy positions, the submucosal dissection speed was remarkably faster in robotic ESD than in conventional ESD in difficult positions (P < 0.05). In difficult positions, there was significantly more muscle damage in conventional ESD than in robotic ESD. (P < 0.05). Conclusions: Dissection speed was greatly improved when assistive robots aided gastric ESD procedures in difficult locations. Our robotic device can thus provide simple, effective, and safe multidirectional traction during gastric ESD in difficult location.
A phase-Ib study of TRK-950 combined with anticancer treatment regimens in patients with gastric and gastro-esophageal junction (GEJ) cancer.
Authors: Cassier Philippe Alexandre , Matrana Marc Ryan , Hanna Diana L. , George Ben , Sharma Sunil , Kelly Ronan Joseph , Okano Fumiyoshi , Von Hoff Daniel D. , Blay Jean-Yves
Published: January 2023

361

Background: TRK-950 is a first-in-class humanized antibody raised against CAPRIN-1 which we have identified as a novel and universal target for cancer therapies. TRK-950 strongly and specifically binds to various cancer cells and shows anti-tumor effects via engagement of immune cells. A series of pre-clinical studies demonstrates its potency and safety. In the phase I study of TRK-950 monotherapy (NCT02990481), it appears safe and well tolerated. No DLT was observed and MTD was not reached at doses of 3-30mg/kg IV weekly. Here, we report on select cohort of the ongoing, multicenter phase Ib study of TRK-950 combined with standard of care (SOC) regimens in patients (pts) with gastric cancer including GEJ cancer (NCT03872947). Methods: Patients with gastric or gastro-esophageal junction (GEJ) cancer and measurable disease were enrolled in phase Ib study, and received paclitaxel on D1, 8, 15 and ramucirumab on D1, 15 of 28-day cycles. In addition TRK-950 was given 10 mg/kg IV weekly. DLT was evaluated during the first cycle. Response was assessed every 2 cycles up to Cycle 6 and every 3 cycles thereafter. Primary endpoint was safety and tolerability. Secondary endpoints included overall response rate (ORR), disease control rate (DCR) per REClST v1.1. Tumor CAPRIN-1 expression was retrospectively assessed by IHC. Results: Nine patients were enrolled, median age 58 yrs; Karnofsky performance status 80 (11%), 90 (67%), 100 (22%); 89% male, 11% female; median number of prior treatments 2 [1, 4]. TRK-950 in combination with ramucirumab and paclitaxel was well tolerated with no DLTs. Most common all-grade treatment-related AEs (TRAEs) were fatigue (67%), vomiting (33%), anemia (22%), nausea (22%), diarrhea (22%), neutrophil count decreased (22%) and decreased appetite (22%). Most common grade ≥ 3 TRAE in ≥ 20% of pts were anemia (22%) and neutrophil count decreased (22%). In 9 response-evaluable pts, ORR was 55.6% and DCR was 100%. Four patients had a screening CAPRIN-1 score of 3+, and all achieved partial response. Conclusions: TRK-950 binds to a newly described target, CAPRIN-1, and has an acceptable safety and tolerability profile when combined with ramucirumab and paclitaxel in gastric cancer including GEJ cancer. Preliminary clinical activity is demonstrated in pre-treated patients with encouraging response rates, particularly enriched by the expression of CAPRIN-1. Further antitumor activity is being confirmed by limiting patients to only 1 prior treatment regimen with an eye towards a randomized trial. Clinical trial information: NCT03872947 .
Safety and efficacy of conversion therapy for esophageal squamous cell carcinoma.
Authors: Tsuji Takayuki , Kawakubo Hirofumi , Takeuchi Masashi , Matsuda Satoru , Fukuda Kazumasa , Nakamura Rieko , Kitagawa Yuko
Published: January 2023

362

Background: The increased efficacy of multimodality treatment allows for the consideration of conversion therapy with curative intent for initially unresectable esophageal squamous cell carcinoma (ESCC) after initial treatment. Conversion therapy has been commonly defined as treatment aiming at a curable intention after tumors initially deemed technically or oncologically unresectable or only marginally resectable respond to chemotherapy. In our institute, conversion therapy is considered for patients with para-aortic lymph node-positive advanced ESCC who have no other distant metastasis, if the para-aortic lymph node metastases have disappeared after systemic chemotherapy. Methods: There were 33 patients of unresectable esophageal cancer with positive para-aortic lymph node metastases from 2011 to 2021. Nine of these patients showed disappearance of para-aortic lymph node metastases and underwent conversion therapy, seven patients underwent esophagectomy and two patients underwent chemoradiation therapy (CRT). Characteristics, short-term and long-term results of these nine cases are studied. Results: All of the nine patients who had para-aortic lymph node metastases were treated with induction DCF (Docetaxel + Cisplatin + 5-FU) therapy as initial treatment. After disappearance of para-aortic lymph node metastasis, minimally invasive or open esophagectomy was performed in seven patients and CRT was performed in two patients. In operation group, four patients (57%) had Clavien-Dindo grade 2 or 3 complications, but no perioperative death was observed. In CRT group, there was no toxicity over CTCAE grade 3. Four of nine patients (44%) had recurrence, within mediastinum lymph node, abdominal lymph node or adrenal gland. 3-year DFS was 56% and 3-year OS was 67%. Conclusions: Conversion therapy is safe and feasible in cases that responded to systemic chemotherapy. Some cases showed good prognosis. Long-term survival is expected with conversion therapy. In our study, there was few cases that could led to conversion therapy. It is expected that more aggressive initial chemotherapy will be used in the future for patients with positive para-aortic lymph node metastases with a view to conversion therapy.