bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality of life (QOL) for patients with esophageal cancer receiving trimodality therapy with induction chemotherapy, chemoradiation, and surgery: Results from CALGB 80803 (Alliance).
Authors: Goodman Karyn A. , Dueck Amylou C. , Fruth Briant , Noonan Anne M. , Shergill Ardaman , Bekaii-Saab Tanios S. , O'Reilly Eileen Mary , Meyerhardt Jeffrey A. , Ilson David H. , Deshields Teresa L.
Published: January 2024

283

Background: The randomized phase II CALGB 80803 trial evaluated use of PET imaging for early assessment of induction chemotherapy (iCT) responsiveness to tailor therapy for patients with esophageal and gastroesophageal junction adenocarcinomas (EC) undergoing trimodality therapy. The primary endpoint of improving pathologic complete response rates using PET-adapted therapy was met. A companion QOL study aimed to characterize patients’ experience through iCT, chemoradiation (CRT) and surgery (S). Methods: Between 11/2011 and 5/2015, 241 eligible patients were randomized to an iCT regimen: modified oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) or carboplatin/paclitaxel (CP), followed by PET scan then CRT, either continuing on the same CT for PET-responders (PET-R) or crossing over to the alternative CT for PET-nonresponders (PET-NR). We prospectively collected QOL domains and symptoms at baseline (T1), after iCT (T2), after CRT (T3), and 3- (T4) and 6- months (T5) after S using the EORTC QLQ-C30, The Esophageal Cancer subscale (EORTC OES18), FACT Neurotoxicity Scale (FACT-NTX), and 6 questions from the PRO-CTCAE. QOL scores were compared between iCT groups and between PET-R and PET-NR at each time point using mixed models. The association of QOL scores at enrollment with overall survival (OS) was tested using Cox regression. Results: 189 patients enrolled on the QOL sub-study, 92 received induction FOLFOX and 97 induction CP. Of those, 110 were PET-R and 79 were PET-NR. 97.9% went on to CRT, and 83.6% underwent S. Global QOL and symptoms statistically significantly worsened from T1 to T2 in 14 of 25 domains, and remained significantly worsened from T1 at: T3 for 19 of 25 domains, T4 for 17 of 25 domains, and T5 for 6 of 25 domains. Changes from T1 significantly favored iFOLFOX (vs iCP) for ability to eat (at T3 and T4), GI symptoms (at T3 and T4), and talking (at T5). Changes from T1 significantly favored iCP (vs iFOLFOX) for neuropathy (at T2, T3, and T4) and coughing (at T5). Proportion of patients reporting worsened PRO-CTCAE scores did not differ between PET-R or PET-NR groups . Multiple QOL domains and symptoms were associated with OS including role functioning, global health status/QOL, appetite loss, pain, dysphagia, and ability to eat (all p<0.002). Conclusions: QOL was impacted most by CRT but returned to baseline 6 months after surgery for most domains. Observed symptom differences did not consistently favor one iCT regimen. Early interventions such as nutritional support and prehabilitation should be studied to improve QOL and OS. Clinical trial information: NCT01333033 .
Short-term and long-term results of robot-assisted esophagectomy in cT3br/T4b esophageal cancer at initial diagnosis: Comparison with conventional thoracoscopic surgery.
Authors: Fujita Takeo , Sato Kazuma , Fujiwara Naoto , Daiko Hiroyuki
Published: January 2024

284

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

285

Background: Sarcopenia is a progressive condition characterized by loss of skeletal muscle mass, muscle strength, and physical function, and is identified as an important prognostic factor in malignant tumors. The patients of gastrointestinal (GI) malignancies are often poor nutrition, weight loss, and loss of skeletal muscle mass due to pathophysiology such as the dysfunction of nutritional absorption and GI obstruction. The prevalence of sarcopenia is high in GI malignancies, especially in advanced gastric cancer (GC), which is reported to be 30%. Recently, in assessing sarcopenia, muscle quality as well as skeletal muscle mass has been considered important and some studies suggest that intramuscular adipose tissue is useful in assessing muscle quality. In this study, we focused on the fat ratio within psoas muscle (FRPM) and sought to clarify the impact of FRPM on overall survival (OS) in GC patients undergoing systemic chemotherapy. Methods: We retrospectively analyzed the patients with histologically confirmed stage IV GC receiving at least one systemic chemotherapy between February 2017 and March 2021 in our hospital. We measured PMI (Psoas Muscle Index: bilateral muscle mass (cm2)/height squared(m2)) and FRPM both at the lumber three level on the CT images before chemotherapy. PMI and FRPM values were classified into two groups, High and Low, according to whether they were higher or lower than the median, and differences in OS were analyzed for each group. Results: The analysis included 79patients (median age: 69 years, 59 males). The median FRPM was 1.67%. The FRPM-high group and the FRPM-low group were 40/39patients, respectively. The median PMI in male and female patients was 4.35 cm2/m2 and 2.88 cm2/m2. Thirty male patients and ten female patients were defined as the PMI-high group, and the remaining 39 patients were in the PMI-low group. The 1, 2 and 3year cumulative OS rate in patients with FRPM-high and FRPM-low was 67.3%, 14.3% and 7.6% in the FRPM-high group and 74.8%, 40.5% and 32.4% in the FRPM-low group ( P = 0.0341). The 1, 2 and 3year cumulative OS rate in patients with PMI-high and PMI-low was 86.7%, 40.4% and 30.0% in the PMI-high group and 55.8%, 12.8% and 6.4% in the PMI-low group ( P < 0.0001). In the multivariate analysis of factors associated with OS, PMI ( P = 0.0047) and FRPM ( P = 0.0019) were independent predictors for the OS. Conclusions: High-FRPM may be associated with declined physical activity, suggesting that skeletal muscle function may be an important prognostic factor in patients with GC receiving systemic chemotherapy.
Tislelizumab (TIS) plus chemotherapy (Chemo) vs placebo (PBO) plus chemo as first-line (1L) treatment of advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJC): Health-related quality of life (HRQoL) outcomes in the RATIONALE-305 study.
Authors: Cruz-Correa Marcia , Xu Rui-Hua , Moehler Markus H. , Oh Do-Youn , Kato Ken , Spigel David R. , Arkenau Hendrik-Tobias , Tabernero Josep , Zimina Anastasia V. , Bai Yuxian , Shi Jianhua , Lee Keun-Wook , Hirano Hidekazu , Wyrwicz Lucjan S. , Pazo Cid Roberto , Xu Hui , Sheng Tao , Barnes Gisoo
Published: January 2024

290

Background: RATIONALE-305 (NCT03777657), demonstrated statistically significant and clinically meaningful improvements in overall survival (OS) with TIS + chemo (n=501) over PBO + chemo (n=496) as 1L treatment in patients (pts) with advanced G/GEJC. This analysis examined HRQoL outcomes of the RATIONALE-305 study at final analysis. Methods: Adults with previously untreated, unresectable, or metastatic GC/GEJC, were randomized (1:1) to TIS 200 mg or PBO IV once every 3 weeks plus investigator-choice of chemo. HRQoL was assessed using EORTC QLQ-C30 and the QLQ-STO22. A mixed model for repeated measures using PRO endpoints at clinical Cycles 4 and 6 was performed. Time to deterioration was examined. Results: TIS + chemo had improved outcomes than PBO + chemo (Table) as indicated by least-squares mean change from baseline to Cycle 6 for QLQ-C30 GHS/QoL (2.52 [95% CI:0.29 to 4.74]), physical functioning (2.46 [95% CI: 0.49 to 4.43]), fatigue (-3.01 [95% CI: -5.78 to -0.24]), and the STO22 index score (-1.62 [95% CI: -3.12 to -0.12]), as well as maintaining upper gastrointestinal (GI) symptoms (-1.74 [95% CI: -3.55 to 0.06)] and pain (-1.88 [95% CI: -4.03 to 0.27]). Pts receiving TIS + chemo had a lower risk for deterioration of GHS/QoL (0.77 [95% CI: 0.60 to 0.98]), physical functioning (0.72 [0.57 to 0.92]), STO22 index score (0.64 [0.45 to 0.92]), pain/discomfort (HR: 0.74 [0.58-0.96]), and upper GI symptoms (0.73 [0.56 to 0.95]). Conclusions: Pts treated with TIS + chemo had better HRQoL outcomes vs pts treated with PBO + chemo, particularly for GHS/QoL, physical functioning, fatigue, GC/GEJC symptoms, pain/discomfort, and upper GI symptoms These results, along with prolonging of OS and other secondary efficacy endpoints, as well as a tolerable safety profile, support the benefit of TIS + chemo as a potential 1L treatment option for GC/GEJC. Clinical trial information: NCT03777657 . [Table: see text]
Association of intensifying supportive care with improved survival in patients with gastric cancer with malignant ascites.
Authors: Karalis John D , Ju Michelle R , Feig Rachel , Estrella Raechelle , Pettigrew Morgan F , Alterio Rodrigo , Abreu Andres A , Farah Emile , Sawas Tarek , Sanford Nina Niu , Sanjeevaiah Aravind , Reznik Scott , Hammer Suntrea , Porembka Matthew R. , Wang Sam C.
Published: January 2024

294

Background: Gastric cancer patients with malignant ascites often have poor functional status and malnutrition that precludes receipt of systemic therapies. Thus, these patients have a very poor prognosis. Beginning in 2019, our multidisciplinary gastric cancer disease-oriented team implemented a more aggressive supportive care plan for gastric cancer patients with malignant ascites. The initiative included measures such as supplemental enteral nutrition, ascites drainage, and initiation of chemotherapy on an inpatient basis. We compared outcomes for gastric cancer patients who presented with synchronous malignant ascites treated before and after the implementation of the care plan. Methods: We performed a retrospective review of our institutional database to identify patients diagnosed with gastric adenocarcinoma and synchronous malignant ascites between 2010-2022. We compared survival between patients diagnosed from 2010-2018, which will be referred to as the historical control era and patients diagnosed from 2019-2022, which will be called the aggressive supportive care era. Results: 54 patients were included in our analysis; 31 patients were treated in the historical control time frame and 23 patients treated during the aggressive supportive care era. Demographic, clinical, and pathologic characteristics were similar between groups. 3% of historical controls received supplemental tube feeds at diagnosis as compared to 30% of the aggressive supportive care cohort (p=0.008). 3% of historical controls received their first cycle of chemotherapy in the inpatient setting versus 39% of patients treated during the aggressive supportive care era (p=0.001). The median number of chemotherapy cycles received was 5 among historical controls and 9.5 among aggressive supportive care era patients (p = 0.02). There was no difference in the number of days spent as an inpatient between the two groups. The median overall survival for historical control patients was 5.4 months as compared to 10.4 months for patients treated during aggressive supportive care era (p=0.035). Conclusions: Gastric cancer patients with synchronous malignant ascites treated during a timeframe when our multidisciplinary team implemented more aggressive supportive care measures had improved OS as compared to historic controls.Our results suggest that aggressive supportive measures for these patients with highly challenging clinical issues and poor prognosis can prolong survival. Specifically, initiation of chemotherapy in the inpatient setting and supplemental nutrition should be considered for patients at high risk for treatment intolerance.
Does routine clinical assessment of older adults with gastroesophageal cancer tell the whole story?
Authors: Connors Meghan , Meeker Caitlin R. , Handorf Elizabeth , Filchner Kelly A. , Tejani Mohamedtaki Abdulaziz , Williams Grant Richard , Winer Arthur , Arora Sukeshi Patel , Vijayvergia Namrata , Dotan Efrat
Published: January 2024

297

Background: Geriatric Assessment (GA) can help oncologists determine fitness of their older patients (pt) for anti-cancer therapy. Our objective was to compare routine provider assessment (PA) and GA of older adults with gastroesophageal cancer (GEC). Methods: Patients ≥65 with any stage of GEC completed a GA. The pt’s provider completed a PA and abnormalities detected by both assessments were centrally reviewed and compared. GA and PA assessed functional status, nutrition, comorbidities, psychological distress, cognition, social support, and chemotherapy toxicity risk. Validated assessment tools were used for the GA. Data collected 3 months post-enrollment included hospitalization, ≥ grade 3 toxicities, and treatment delays. We compared the proportions detected/not detected abnormalities by PA vs GA using McNemar’s test for paired data, and we measured agreement using Kappa statistics (1=full, 0=no, -1=disagreement). Results: 82 pts were enrolled, majority male (74%), median age 73 (65-91), stage III/IV (82%) disease on first line therapy (79%). Cancer sites included gastric (32%), esophageal (43%), GEJ (26%). Pts’ demographic and clinical characteristics did not predict for the identification of GA abnormalities. GA detected 196 abnormalities and PA detected 86. Majority of pts (84%) had ≥ 1 unidentified abnormality by PA. Providers identified more pts with clinically significant comorbidities as compared to GA. However, the GA identified more abnormalities compared to PA in all other evaluated domains (Table). Low agreement was found between PA and GA in any of the domains. Pts scoring high on the CARG chemotherapy toxicity prediction tool (p=0.004) and pts with evidence of psychological distress (p=0.049) had more ≥ grade 3 toxicity. Pts with abnormalities in functional status, nutrition, psychological distress, and a high CARG score were more likely to be hospitalized during therapy. Conclusions: Clinical characteristics of older pts with GEC are not predictive of GA abnormalities. While providers were better at identifying comorbidities, the GA resulted in a comprehensive evaluation of all domains and identified significant abnormalities that affect treatment outcomes in this population. [Table: see text]
Symptom burden in patients with early-onset colorectal cancer: A subgroup analysis of the enhanced, EHR-facilitated cancer symptom control (E2C2) trial.
Authors: Storandt Michael H. , Kour Oudom , Ruddy Kathryn Jean , Cheville Andrea L. , Pachman Deirdre R. , Rahman Parvez , Wilder Smith Ashley , Mitchell Sandra A. , Shi Qian , Jin Zhaohui
Published: January 2024

31

Background: Incidence of early-onset colorectal cancer (eoCRC, <50 years of age at diagnosis) is increasing globally. However, little is known regarding symptom burden in this sub-population. We compared symptoms in patients with eoCRC to those of patients with average-onset CRC (aoCRC, diagnosed at age ≥ 50). Methods: E2C2 is a stepped-wedge, cluster-randomized pragmatic trial evaluating a collaborative care model for the assessment and management of six symptoms [Sleep disturbance, Pain, Physical function impairment, Anxiety, emotional Distress, and Energy deficit (SPPADE)]. Patients were asked to complete assessments rating each of these symptoms on an 11-point numerical rating scale. Symptom severity was classified as mild (0-3), moderate (4-6), or severe (7-10). We conducted a subgroup analysis of patients with CRC, comparing SPPADE symptoms on an initial survey, regardless of timing in treatment course, between patients with eoCRC and aoCRC. Results: Patients with CRC (n=4281) completed a survey between March 2019 and December 2022. Patient demographics and SPPADE symptoms are reported in the table. Patients with eoCRC were more likely to report severe sleep disturbance ( p<0.0001), pain ( p=0.03485), anxiety ( p<0.0001), emotional distress ( p<0.0001), and fatigue ( p=0.01083). In patients with eoCRC, women were more likely to report severe pain (12.6% vs 6.9%, p=0.0069), anxiety (16.1% vs 10.0%, p=0.012), emotional distress (12.1% vs 5.4%, p=0.00066), fatigue (18.9% vs 13.4%, p=0.038), and physical function impairment (10.1% vs 5.8%, p=0.026) compared to men. Conclusions: Patients with eoCRC reported higher symptom severity than patients with aoCRC. This suggests unique needs for symptom management in patients with eoCRC. Additional research is needed to evaluate how time since diagnosis, disease characteristics, cancer-directed treatment patterns, and co-occurring symptoms are associated with specific symptoms in this population. [Table: see text]
Clinical outcomes of early gastric cancer resected by endoscopic submucosal dissection at young age.
Authors: Park Jong-Jae , Joo Moon Kyung , Kim Jun Hee , Kwon Chan Mi , Kang Ji Min , Kang Min Hyung , Lee Si Eun , Kim Sunsuk , Kim Won Shik , Kim Seung Han , Lee Beom Jae , Chun Hoon Jai
Published: January 2024

314

Background: A small portion of patients are diagnosed as early gastric cancer (EGC) and undergo endoscopic submucosal dissection (ESD) at young age, however, their clinical outcomes are rarely known. We investigated clinical characteristics and outcomes of patients who underwent ESD for treatment of EGC at age under 50. Methods: We enrolled patients who were diagnosed as EGC and underwent ESD during 2006 and 2020. We divided them either for young age (YA) group if age ≤ 50 years and other age (OA) group if > 50 years. Results: We enrolled 1,349 patients (YA group: 105 patients [7.8%], OA group: 1244 [92.2%]). Compared with OA group, YA group contained more female patients (36.2 vs. 26.5%, P= 0.033), their tumor was located at middle third (41.0 vs. 29.6%, P= 0.006) and was depressed (40.0 vs. 28.8%, P= 0.001), and had more undifferentiated (30.5 vs. 12.1%, P< 0.001) and diffuse type (22.9 vs. 7.3%, P< 0.001) histology. However, synchronous tumor was less frequent in YA group (2.9 vs. 12.4%, P= 0.001). When we sorted 884 patients who achieved curative resection and were followed-up longer than 12 months, Kaplan-Meier analysis showed that metachronous neoplasm (dysplasia or cancer) and metachronous cancer were significantly less in YA group than OA group ( P= 0.003 and 0.013, respectively), however, local recurrence was not significantly different between two groups. Conclusions: ESD is a favorable and effective therapeutic modality for EGC patients who are aged under 50, once curative resection is achieved.
Phase 2 study of cabozantinib (Cabo) and pembrolizumab (Pembro) in metastatic gastric/gastroesophageal adenocarcinoma (mGEA) resistant or refractory to immune checkpoint inhibitors (ICI).
Authors: Dayyani Farshid , Chao Joseph , Lee Fa-Chyi , Taylor Thomas H. , Neumann Kristen , Cho May T
Published: January 2024

315

Background: Most mGEA patients (pt) progress on therapy including ICI, with about 5% progression-free at 6 mo (PFS-6) with single agent ICI in later lines of therapy. Alternative therapeutic approaches are needed. Cabo is a multi-tyrosine kinase inhibitor thought to enhance the immunomodulatory effects of ICI. This study reports on safety and efficacy of the combination of Cabo+Pembro in mGEA resistant or refractory to ICI. Methods: Investigator-initiated, single‐arm, single institution, phase 2 study in pts with mGEA after ≥1L of fluoropyrimidine and platinum-containing regimens. Pts with a PD-L1 CPS score ≥10% had also progressed on ICI. Cabo dose was 40mg p.o. daily on days 1 through 21 of a 21‐day cycle, with Pembro 200 mg i.v. on day 1. The primary endpoint was PFS-6, with H0=5%, Ha≥20%, requiring n=27 evaluable pts and n≥4 pts with PFS-6 to reject H0 in favor of Ha. Results: 27 pts were enrolled. Median age 58 years (24-87), female (n=14), ECOG 0/1= 13/14, GC/GEJ= 16/11, Non-Hispanic White/Hispanic/Asian= 12/8/7. The primary endpoint was met with n=6 pts having PFS>6mo. After a median follow-up of 31.4mo (range 3.3-42.5), PFS-6 is 22.2% (95% CI 9.0-39.0). The median PFS and OS are 2.3mo (95% CI 1.7-4.1) and 5.5mo (3.1-14.0), respectively. The most common mutations were TP53 (78.3%) and CDH1/PIK3CA/CTNNB1 (17.4% each). In exploratory analyses, 5/7 (71.4%) pts in the top quartile for PFS had alterations in the cMET-PI3K-AKT pathway. The most common any grade (G) treatment related adverse events (TRAE) were diarrhea (25.9%), fatigue (18.5%), hypertension and muscle cramps (14.8% each). G3-4 TRAE were seen in n=3 pts (Hypertension, Thromboembolic event, esophageal perforation; each n=1). No G5 were observed. Conclusions: The addition of Cabo to Pembro shows clinical benefit in ICI resistant or refractory mGEA with an observed PFS-6 of 22.2%. The regimen appears tolerable with no new safety signals. An exploratory association of alterations in the cMET-PI3K-AKT pathway with prolonged PFS needs to be confirmed in a larger cohort. Clinical trial information: NCT04164979 .
Network meta-analysis of global trials of 1L therapies in locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma.
Authors: Shah Manish A. , Shitara Kohei , Lonardi Sara , Chao Yee , Yamaguchi Kensei , Kukielka-Budny Bozena , Ryu Min-Hee , Ungureanu Andrei , Oh Mok , Chang Lawrence , Yang Hongbo , Chai Xinglei , Bhattacharya Pranob P. , Matsangou Maria , Ranganath Radhika , Ajani Jaffer A. , Xu Rui-Hua
Published: January 2024

325

Background: The phase 3 SPOTLIGHT (NCT03504397) and GLOW (NCT03653507) studies reported statistically significant improvement in PFS and OS with 1L zolbetuximab (anti-claudin-18 isoform 2 [CLDN18.2]) + mFOLFOX6 or CAPOX in pts with CLDN18.2+, HER2−, LA unresectable or mG/GEJ adenocarcinoma. This network meta-analysis (NMA) indirectly compared the relative efficacy of 1L therapies. Methods: A systematic literature review of phase 2, 3, or unknown phase randomized, global trials of 1L therapies (capecitabine + cisplatin [CX]; capecitabine + oxaliplatin [CAPOX]; fluorouracil + cisplatin [CF]; oxaliplatin + folinic acid + fluorouracil [FOLFOX]; S-1 + cisplatin [SC]; nivolumab + CAPOX/FOLFOX; pembrolizumab + CF/CAPOX or CX; and zolbetuximab + CAPOX/FOLFOX) in adults with LA unresectable or mG/GEJ adenocarcinoma. To form a connected main network, FOLFOX and CAPOX were assumed equally efficacious and combined. In the latest publicly available data, hazard ratios (HRs) of PFS and OS for intent-to-treat (ITT) populations were extracted or reconstructed from Kaplan-Meier curves when not reported as inputs for Bayesian fixed-effects NMAs. Comparative effectiveness was reported using median HR and 95% credible intervals (CrIs). Results: Trials reporting ITT populations were included, resulting in 9 trials (6663 pts) for PFS analysis and 10 trials (6735 pts) for OS analysis representing 8 regimens. Pts were randomly assigned to an experimental arm vs FOLFOX/CAPOX. Pts on 1L zolbetuximab, nivolumab, or pembrolizumab in combination with CF/CAPOX or FOLFOX/CAPOX had significantly reduced risk of disease progression or death vs FOLFOX/CAPOX (Table). Zolbetuximab + FOLFOX/CAPOX had the highest probability of being ranked first in treatment efficacy for both PFS (probability =0.54) and OS (0.36); followed by pembrolizumab + CX (0.27) and pembrolizumab + CF/CAPOX (0.13) for PFS; and by pembrolizumab + CF/CAPOX (0.3) and nivolumab + FOLFOX/CAPOX (0.24) for OS. Conclusions: This NMA examined the relative benefit of different targeted therapies when combined with chemotherapy. Zolbetuximab + FOLFOX/CAPOX for CLDN18.2+, HER2−, LA unresectable or mG/GEJ adenocarcinoma confers a significant PFS and OS benefit, similar to that achieved with PD-1/PD-L1 inhibitors + CF/CAPOX or FOLFOX/CAPOX. [Table: see text]
Efficacy and safety of fruquintinib with nab-paclitaxel in advanced G/GEJ cancer after exposure to immune checkpoint inhibitors: A single-center prospective clinical trial.
Authors: Ma Xiaoting , Ou Kai , Liu Xiu , Wang Qi , Gao Lizhen , Sun Yongkun , Yang Lin
Published: January 2024

327

Background: Immune checkpoint inhibitors (ICIs) expanded choices of early-line therapies in advanced gastric (G)/gastro-esophageal junction (GEJ) cancer. In addition, it’s observed that early-line ICI therapy, compared to chemotherapy, could enhance the efficacy of VEGFR inhibitors with chemotherapy in late lines. This single-center prospective clinical trial was aimed to explore the efficacy and safety of fruquintinib with nab-paclitaxel as second-line in patients (pts) with G/GEJ cancer exposed to ICIs in early lines. Methods: This is a single-center, prospective, open-label clinical trial. Pts with advanced G/GEJ cancer who had been exposed to ICIs before the second line were eligible. 42 pts would receive 100g/m2 nab-paclitaxel on day 1 and day 8 every 3 weeks, and 4mg fruquintinib from day 1 to day 14 every 3 weeks. Progression-free survival (PFS) was set as the primary endpoint. The Kaplan–Meier method would be used to evaluate time-to-event outcomes. Results: Up to Aug 10, 2023, 25 pts had been enrolled, 23 of whom were evaluable. 14 (60.9%) pts in evaluable set were male. All these pts was with stage Ⅳ of TNM staging. The median age was 58 (range: 33-74), and 6 (26.1%) pts were elder than 65 yr. 12 (63.2%) pts were with PD-L1 CPS greater than 1, 9 (47.4%) pts greater than 5, and 4 (17.4%) pts greater than 10. PD-L1 CPS of 4 pts was unknown. The pts had received a median of 5 (range: 1-20) cycles in early-line ICI therapy. 17 (73.9%) pts suffered metastasis in retroperitoneal lymph node and 7 (30.4%) pts in liver. With a median follow up time of 5.6 (range: 2.1-16.6) mo, the PFS achieved 4.8 (95% CI: 4.6-NA) mo. Despite the immatureness of overall survival (OS), the 1-year OS rate was 56.25% (95% CI: 17.27%-95.23%). The ORR was 47.8% (n=11), and DCR was 100% (n=23). As to safety, the most common (≥20%) AEs of all grades were white blood cell decrease, peripheral sensory neuropathy, and neutrophil count decrease, while that of grade≥3 was white blood cell decrease. Conclusions: Fruquintinib with nab-paclitaxel as second-line therapy demonstrated good efficacy and safety in advanced G/GEJ cancer after exposure to ICIs. ICIs might increase benefit from this therapy, which warrants further investigations in a large cohort. Clinical trial information: ChiCTR2200059976 .
Clinical outcomes of argon plasma coagulation for the treatment of gastric low-grade dysplasia.
Authors: Wang Hoyoung , Choi Kee Don , Noh Jin Hee , Na Hee Kyong , Jung Kee Wook , Ahn Ji Yong , Lee Jeong Hoon , Kim Do Hoon , Song Ho June , Lee Gin Hyug , Jung Hwoon-Yong
Published: January 2024

336

Background: Argon plasma coagulation (APC) could be considered a treatment modality for small gastric low-grade dysplasia (LGD) instead of endoscopic resection (ER). Our study investigated the clinical outcomes of APC for treating gastric LGD and associated variables with local recurrence. Methods: This study included 911 patients who underwent APC for gastric neoplasms at the tertiary hospital from July 2007 to March 2022 with a minimal follow-up of 12 months. 112 subjects without any information about H. pylori infection status, 164 subjects who underwent APC for salvage therapy, 5 subjects with high grade dysplasia, and 12 subjects with cancer were excluded. Through a retrospective review of medical data, the clinical outcomes and variables associated with the local recurrence were analyzed. Results: A total of 618 patients with LGD (median age of 64 years old) were followed up for a median of 30 months and local recurrence has happened in 21 patients (3.4%). Multivariate analysis showed lesion size (hazard ratio 1.06, 95% confidential interval 1.01–1.12) was associated with the local recurrence. Among 557 lesions smaller than 10 mm, local recurrence was found in 14 cases (2.6%) and local recurrence was in 7 cases (9.5%) of 109 tumors larger than 10 mm ( p <0.004). Conclusions: In gastric LGD smaller than 10 mm without scars, APC is a good treatment modality in place of ER. However, when a lesion is larger, APC should be selected carefully with close monitoring. [Table: see text]
Phase I trial of intraperitoneal paclitaxel in patients with gastric adenocarcinoma and peritoneal carcinomatosis or positive peritoneal cytology.
Authors: Badgwell Brian D. , Blum-Murphy Mariela A. , Ikoma Naruhiko , Estrella Jeannelyn , Li Jenny Jing , Kawedia Jitesh D. , Mansfield Paul F. , Ajani Jaffer A.
Published: January 2024

360

Background: The purpose of this Phase I trial was to evaluate the safety and toxicity of repeated normothermic intraperitoneal paclitaxel for patients with gastric cancer metastatic to the peritoneum. Methods: In patients with gastric adenocarcinoma and peritoneal carcinomatosis or positive peritoneal cytology, a Bayesian optimal interval design was used to prospectively identify the safety and tolerability of escalating doses of intraperitoneal paclitaxel administered as 3 weekly treatments followed by a 1-week break and then 3 additional weekly treatments. The primary objective was to define the maximum tolerated dose (MTD). Secondary objectives included determining the safety and tolerability of escalating doses of intraperitoneal paclitaxel and making a preliminary assessment of the anti-tumor activity based on the peritoneal carcinomatosis index (PCI) and overall survival (OS). Results: A total of 25 patients were treated between January 2020 and April 2023. The MTD for intraperitoneal paclitaxel was 100 mg/m2. Five patients (20%) had dose-limiting toxic effects at 100 mg/m2. Treatment-related grade 3-4 toxic effects included leukopenia in 8 patients (32%) and neutropenia in 8 (32%). Seven patients (28%) required a schedule change to every-other-week treatment. The PCI after intraperitoneal paclitaxel demonstrated progression in 5 patients (20%), stable disease in 5 (20%), and improvement in 10 (40%); 5 patients (20%) were not evaluable for PCI. Eight patients (32%) had resolution of their peritoneal disease, and 7 (28%) underwent attempted resection. The median OS from the time of diagnosis of metastatic disease was 17.9 months (95% CI 14.5-29.5) and from the date of treatment initiation was 10.3 months (95% CI 6.5-18.8). One-, 2-, and 3-year OS rates from the time of diagnosis of metastatic disease were 84%, 36%, and 22%, respectively. Pharmacokinetic analysis showed there was systemic absorption of paclitaxel and plasma AUC0-∞ and Cmax was (13955 ± 6683 h.ng/ml) and (390 ± 191 ng/ml) respectively, while intraperitoneal concentration at the end of infusion was 232 ± 65 µg/ml. Conclusions: Paclitaxel may be safely administered at an intraperitoneal dose of 100 mg/m2. Neutropenia was common with weekly treatments, and we would recommend every-other-week treatment for future studies. Rates of resolution of peritoneal disease with multimodality therapy were promising, supporting future trials of this strategy and molecular profiling to identify factors associated with treatment response. Clinical trial information: NCT04220827 .
Safety and efficacy of zolbetuximab for CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: A systematic review and meta-analysis of randomized controlled trials.
Authors: Celso Davi Said Gonçalves , Reis Pedro Cotta Abrahão , Escalante-Romero Lorena , Dacoregio Maria Inez , Gomy Israel , Marin Comini Ana Carolina , Camandaroba Marcos Pedro Guedes
Published: January 2024

370

Background: Monoclonal antibody (Nivolumab, Trastuzumab, Bemarituzumab) with chemotherapy has shown benefit for patients with metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. Zolbetuximab, a new monoclonal antibody against Claudin (CDLN) 18.2 has demonstrated interesting results in clinical trials, however, there is still a need to find a safe and effective first-line treatment, especially for epidermal growth factor receptor (HER) 2-negative patients. Therefore, we aimed to perform a meta-analysis exploring the use of combined immunotherapy (Zolbetuximab) and standard chemotherapy versus chemotherapy alone. Methods: We searched PubMed, Embase and Cochrane Central for randomized controlled trials (RCTs) comparing Zolbetuximab to chemotherapy alone in patients with CLDN18.2-positive gastric or GEJ adenocarcinoma. The outcomes evaluated were Overall Survival (OS), Progression Free-Survival (PFS), Objective Response Rate (ORR) and Treatment-Emergent Adverse Events (TEAE). We pooled hazard ratio (HR) for PFS and OS endpoints and risk ratio (RR) for ORR and TEAE, with 95% confidence intervals (CI). Statistical analyses were performed using R software version 4.3.1 with a random-effects model. I² analysis was used to assess heterogeneity. Adverse Events (AE) were graded according to the National Cancer Institute Common Terminology Criteria for AE. Results: From sixty-six studies, three were included, with a total of 1349 patients. 671 (49.7%) were part of the intervention group, 769 (57.0%) were male, 360 (26.7%) underwent prior gastrectomy and 1304 (96.7%) had a more than 70% CLDN18.2 cellular staining rate. Age range was 21-83 years. Treatment with Zolbetuximab was associated with significantly higher PFS (HR 0.64; CI 0.49-0.84; p = 0.0011; I² = 59.6%) and OS (HR 0.70; CI 0.59-0.84; p<0.0001; I² = 40.0%). TEAEs grade ≥ 3 (RR 1.09; CI 1.03-1.16; p = 0.0051; I² =0.0%) were greater for the intervention group. ORR and serious TEAE had no difference when compared with the control group. Most frequent AEs were nausea (34.6%), vomiting (30.2%) and decreased appetite (18.6%). Conclusions: In summary, the use of Zolbetuximab alongside standard chemotherapy reduces mortality and disease progression, although it might increase the risk for grade ≥ 3 treatment-emergent AEs.
Camrelizumab combined with concurrent chemoradiotherapy for locally recurrent esophageal cancer: A single-arm, open-label study.
Authors: Jia Ruinuo , Zhang Junqian , Zhang Yaowen , Li Shuoguo , Sheng Manxi , Ma Jianguang , Zheng Anping , Tian Chuntao , Wang Jianli , Li Liuyan , Gao Shegan
Published: January 2024

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Background: Local recurrence is the main failure pattern after radical treatment of esophageal cancer. There is no uniform treatment specification for such patients(pts) so far. The combination of immune checkpoint inhibitors and concurrent chemoradiotherapy (CCRT) has emerged as a novel strategy to treat esophageal cancer. This research was to evaluate the efficacy and safety of camrelizumab (ICI targeting PD-1) combined with CCRT in the treatment of locally recurrent esophageal cancer. Methods: This open clinical study planned to enroll 62 pts with locally recurrent esophageal cancer following radical treatment who aged 18-75 years with ECOG performance status of 0-1. Pts received the following treatments: camrelizumab (200 mg q2w, continuous medication until disease progression, intolerable toxicity, or withdrawal); simultaneous radiotherapy (the total radiation dose was 50-50.4 Gy, which was given by 25-28 fractions, 5 fractions per week, with 1.8-2 Gy for each fraction); chemotherapy (capecitabine, 625mg/m2, bid, oral, d1-5, qw, total 5 weeks). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Results: Between Feb 2022 and Jul 2023, 14 pts with a median age of 71 years old had been enrolled. Among the evaluable pts, the ORR was 69.2% (9/13), the DCR was 100.0% (13/13). With a median follow-up of 16.0 months (95% CI 13.5-18.5), the median PFS was 7.6 months (95% CI 4.2–11.0), the median OS was 18.6 months (95% CI NE–37.6) in the full analysis set. The incidence of any grade adverse events (AEs) was 100.0% and that of grade ≥3 AEs was 57.1% of 14 pts. The most common AEs included lymphocyte count decreased (11/14, 78.6%), neutrophil count decreased (5/14, 35.7%), white blood cell count decreased (5/14, 35.7%) and anemia (5/14, 35.7%). The most grade ≥3 AE was lymphocyte count decreased (6/14, 42.9%). No new safety signals or treatment-related deaths were observed. Conclusions: Current results suggested the promising efficacy and acceptable safety of camrelizumab combined with CCRT in pts with locally recurrent esophageal cancer. The study enrollment is ongoing, and further survival and safety data will be reported in the future. Clinical trial information: NCT04390945 .
Gastric microbiome signature to predict metachronous recurrence after endoscopic resection of gastric neoplasms.
Authors: Lee Hokyoung , Shin Cheol Min , Chang Young Hoon , Yoon Hyuk , Park Young Soo , Kim Nayoung , Lee Dong Ho
Published: January 2024

399

Background: It is well-established that the gastric microbiota undergoes significant alterations during the process of gastric carcinogenesis. This study aimed to identify gastric mucosa-associated microbiome (MAM) for the prediction of metachronous recurrence after endoscopic resection of gastric neoplasms. Methods: Subgroup analyses were conducted for 81 patients (early gastric cancer: dysplasia = 55:26) from a prospective cohort (Clinical Trials No. NCT04830618). Demographic data, and history of Helicobacter pylori eradication therapy, endoscopic and histologic findings were incorporated. The profile of Gastric MAM obtained from non-cancerous corporal biopsy specimens and was analyzed by 16S rDNA sequencing. Results: Over a median follow-up duration of 53.8 months, 16 metachronous gastric neoplasms (10 adenomas and 6 adenocarcinomas) developed. Baseline gastric MAM varied with H. pylori infection status, but was unaffected by the presence of atrophic gastritis, intestinal metaplasia or synchronous lesions. The group with metachronous recurrence did not exhibit distinct phylogenetic diversity compared with the group devoid of recurrence. β-diversity analysis showed significant difference between the two groups (weighted UniFrac distance, PERMANOVA p = 0.006). In the LEfSe analysis, metachronous recurrence group had an increased abundance of Corynebaceriaceae, Comamonadaceae, Corynebacterium, Curvibacter, and a decreased abundance of Helicobacteraceae, and Helicobacter. The total study population were classified into two distinct gastrotypes by baseline Gastric MAM (gastrotype 1: Helicobacter-dominant, gastrotype 2: Akkermansia-abundant). MAM of gastrotype 1 had higher abundance of Helicobacter pylori, and lower abundance of Akkermansia¸ Comamodaceae, Muribaculacae , Streptococcus, Corynebacteriaceae , Cutibaterium. Patients in gastrotype 2 showed higher risk of metachronous recurrence than gastrotype 1 (hazard ratio = 4.621 by Cox proportional hazard model, p-value = 0.0185). Conclusions: Gastric cancer patients can be classified into two distinct gastrotypes by their MAM profiles, which were associated with different risk of metachronous recurrence. MAM profiling of gastric cancer patients is expected give insight into their risk of metachronous recurrence. Clinical trial information: NCT04830618 .
De-risking 1st line chemotherapy-free immune checkpoint inhibitor (ICI) use for patients with advanced gastroesophageal cancer (aGEJ) with tumor mutational burden (TMB).
Authors: Klempner Samuel J. , Quintanilha Julia , Aboosaiedi Ali , Morley Samantha , Mitchell Jerry W. , Ross Jeffrey S. , Graf Ryon
Published: January 2024

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Background: ICI + chemotherapy (chemo-ICI) is becoming an increasingly common 1st line regimen for patients with aGEJ. However, direct outcome comparison between biomarker-enriched groups receiving chemo-ICI vs. ICI monotherapy (mono-ICI) is limited in phase III trials. We sought to evaluate if TMB might identify patients for whom mono-ICI vs. chemo-ICI might be de-risked. We prospectively hypothesized that (1) patients with TMB <10 mut/mB would have more favorable outcomes receiving ICI-chemo vs. mono-ICI and (2) patients with TMB ≥10 mut/mB would have diminished additional benefit from chemo-ICI vs. mono-ICI. Methods: This study included patients with aGEJ who received 1st line chemo-ICI or mono-ICI and tumor tissue genomic profiling by Foundation Medicine. Patient data was obtained by the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine gastric real-world clinico-genomic database (FH-FMI CGDB), originating from approximately 280 US cancer clinics (January/2011–March/2023). Real-world progression-free survival (rwPFS) and overall survival (rwOS) were compared between patients receiving chemo-ICI vs. mono-ICI by Cox models, adjusted by propensity scores accounting for disease stage at diagnosis, ECOG PS, PD-L1 score and microsatellite instability (MSI) status. Comparisons of the explanatory power of TMB (<10 vs. ≥10 mut/mB) vs. MSI status (MSI-H vs MSS) were performed by likelihood ratio test (LRT). Results: A total of 263 patients (176 receiving chemo-ICI and 87 mono-ICI) were included in the study. Patients with TMB <10 mut/mB had more favorable outcomes receiving chemo-ICI vs. mono-ICI for rwPFS (median 5.8 vs. 1.9 months, hazard ratio [HR]: 0.44, 95% confidence interval [CI] 0.26-0.76), p=0.0029) and rwOS (median 11.1 vs. 7.9 months, HR: 0.68, 95% CI 0.40-1.15, p=0.1489). Patients with TMB ≥10 mut/mB did not have reduced benefit from mono-ICI; curiously less favorable outcomes were observed with chemo-ICI vs. mono-ICI for rwPFS (HR: 3.27, 95% CI 1.19-8.97, p=0.0212) and rwOS (HR: 3.56, 95% CI 1.14-11.08, p=0.0286). Evaluating only the mono-ICI group, the LRT indicated that when TMB was added to a model evaluating only MSI status, there was an improvement in ICI outcome prediction (p=0.006 for rwPFS and p=0.003 for rwOS), but not when MSI was added to TMB (p=0.91 for rwPFS and p=0.40 for rwOS). Conclusions: aGEJ patients with TMB <10 mut/mB had more favorable outcomes receiving chemo-ICI vs. mono-ICI. In the TMB ≥10 mut/mB we did not observe more favorable outcomes among patients receiving chemo-ICI vs. mono-ICI. Curiously, we observed more favorable outcomes among those receiving mono-ICI in the TMB ≥10 mut/mB group. Among patients receiving mono-ICI, TMB better predicted mono-ICI outcomes compared to MSI status alone.
Revisiting non-invasive diagnosis of hepatocellular carcinoma in clinical reality.
Authors: Teufel Andreas , Qian Yuquan , Lu Qiaoyuan , Rodriguez Isaac , Min Xiangde , Froelich Matthias , Ümütlü Muzaffer Reha , Castrillon German A , Alaffita Carlos Romero , Garay Mora Juan Alberto , Guo Zhiqiang , Weiss Christel , Schönberg Stefan O. , Ebert Matthias Philip , Sun Ying-Shi
Published: January 2024

441

Background: Current guidelines emphasize the use of CT or MRI for hepatocellular carcinoma (HCC) diagnosis, with strict regulation of biopsies. However, Hepatocellular-Cholangiocarcinoma (cHCC-CC), a liver cancer variant displaying histological elements of both HCC and cholangiocellular carcinoma (CCC), typically exhibits radiological features of both HCC and CCC on imaging studies. Additionally, platinum drugs represent the most promising initial treatment option for patients with unresectable or advanced cHCC-CC, deviating significantly from the treatment approach for HCC. Consequently, our study aims to assess the efficacy of imaging techniques in distinguishing between HCC, CCC, and cHCC-CC, highlighting its clinical significance. Methods: We conducted a database search to identify patients diagnosed with HCC, CCC, and cHCC-CC from June 2010 to September 2020. After implementing quality control measures, our study comprised 68 MRI scans from patients, including 30 with HCC, 23 with CCC, and 15 with cHCC-CC. Histological evidence confirming the diagnoses was obtained within a maximum of four weeks before or after the MRI scans. Subsequently, seven radiologists from Asia, Europe, North America, and South America, including abdominal imaging experts (AIEs) and non-abdominal imaging experts (NIEs) or trainees, independently and blindly assessed the MRI scans. They evaluated various MRI features and established a differential diagnosis encompassing HCC, CCC, and cHCC-CC. Results: The AIEs demonstrated high proficiency in utilizing MRI images exclusively for diagnosing HCC (70%-100%) and CCC (73.9%-91.3%). They significantly outperformed NIEs/trainees (all p values < 0.01), achieving accuracy rates of 26.7%-66.7% for HCC and 21.7%-60.9% for CCC. However, their ability to accurately distinguish cHCC-CC (6.7%-53.3%) was limited and comparable to NIEs/trainees (26.7%-46.7%). Additionally, there was greater consistency in MRI feature assessment among AIEs for HCC and CCC when compared to cHCC-CC. Notably, no significant differences were observed in the impact of a cirrhotic background on the diagnosis of HCC and cHCC-CC among AIEs. Furthermore, there was no significant intercontinental variability in overall liver cancer diagnosis and the diagnosis rates of the three types of liver cancer by AIEs. Conclusions: MRI imaging demonstrated effective differentiation between HCC and CCC, especially when interpreted by experts in abdominal imaging. Nevertheless, the ability to accurately detect cHCC-CC was notably constrained across all participating radiologists. Consequently, liver biopsy continues to play a pivotal role in ensuring diagnostic precision and facilitating the selection of appropriate medical treatment strategies.