bluuebunny/crossref_metadata_2025 huggingface dataset:
Urban/rural disparities in stage at presentation of colorectal cancer among young adults in the United States, 2007-2015.
Authors: Nguyen Victoria , Delgado David J. , Denneny Rachel Gray , Subramoney Jay , George Brandon , Mitchell Edith P.
Published: May 2019

3598

Background: The overall incidence rate of colorectal cancer (CRC) has declined in recent decades but is rising in young adults (YA). Disparities also exist in CRC presentation and geographical residence. We examined associations between urban/rural residence and CRC stage at presentation among YA 18-50 years old, using the Surveillance, Epidemiology, and End Results (SEER) 1973-2015 registry. Methods: Retrospective cohort study using SEER patients (pts) diagnosed with CRC between 2007-2015, aged 18-50. Urban/rural status was defined at the county level as large metro, small metro, urban non-metro, and rural. Pts were grouped by age: 18-30, 31-40, and 41-50 years old. Stage was defined as in-situ/localized and regional/distant. We used multivariable logistic regression to describe associations between urban/rural status with stage at presentation, adjusting for tumor location, histology, grade, and patient attributes (e.g. insurance status). Results: 27,198 CRC pts were analyzed: 62.2% large metro, 27.4% small metro, 9.4% urban non-metro, and 67.1% regional/distant stage. In multivariable analysis, YA in urban non-metro counties had lower odds of regional/distant stage at presentation compared to YA in large metro counties (OR = 0.87, 95% CI = 0.79-0.97). Associations between small metro and rural status with stage at presentation were not significant (OR = 0.94, 95% CI = 0.89-1.01 and OR = 0.84, 95% CI = 0.64-1.10, respectively). YA with Medicaid or no insurance had higher odds of regional/distant CRC (OR = 1.28, 95% CI = 1.17-1.39 and OR = 1.34, 95% CI = 1.20-1.51, respectively) compared to YA privately insured. Other factors in YA associated with higher odds of regional/distant CRC included signet-ring histology, poorly-, moderately-, and undifferentiated grade, and younger age (18-30 and 31-40 years old). Conclusions: YA in urban non-metro areas had lower odds of regional/distant CRC at presentation compared to YA in large metro areas. YA with Medicaid, no insurance, signet-ring histology, poorly-, moderately-, and undifferentiated grade, and younger age had higher odds of regional/distant CRC at presentation. Further research is needed to explore the etiology of these differences.
Methylated DNA markers (MDMs) in primary (pCRC) and metastatic colorectal cancers (mCRC).
Authors: Xie Hao , Mahoney Douglas W. , Peterson Molly M , Foote Patrick H. , Burger Kelli , Doering Karen A , Taylor William R. , Cao Xiaoming , McGlinch Maria , Berger Calise K. , Wu Tsung-Teh , Hubbard Joleen Marie , Ahlquist David A. , Kisiel John B.
Published: May 2019

3599

Background: Existing tools for post-treatment CRC surveillance and monitoring are insensitive and expensive. MDMs are broadly informative for early detection of CRC but have not been extensively studied for disease monitoring. As a first step, we sought to assess the concordance of novel CRC-associated MDMs in pCRC and mCRC. Methods: A panel of 14 MDMs previously identified to be highly discriminant for pCRC was selected on the basis of high median fold-change of MDM levels relative to buffy coat (682 (IQR: 132-19347)). Surgically resected pCRC and paired mCRC were identified from institutional pathology databases. Quantitative methylation-specific PCR was used to assay MDMs. 30 paired samples per metastatic subtype were calculated to be sufficient. MDM levels were compared using two-sample and paired Wilcoxon rank sum tests. Results: 87 patients with paired pCRC and mCRC including 57 synchronous and 30 metachronous metastases were included. 41/87 (47%) had neoadjuvant and 59/87 (68%) had adjuvant chemotherapy. All synchronous metastases were to liver. Metachronous metastases were to liver in 19/30 (63%) and to lung in 11/30 (37%). The levels of 14 selected MDMs were remarkably similar between paired pCRC and mCRC (Table). Individual MDM levels and the average level of all MDMs combined were not significantly different ( p> 0.0018 by Bonferroni correction). Conclusions: MDM levels are highly concordant in pCRC and mCRC. Thus, MDMs discovered from pCRC should be further studied for non-invasive surveillance after surgical resection and monitoring of treatment response in mCRC. [Table: see text]
Differences in clinical outcomes in young-onset colorectal cancer based on ethnicity in an NCI designated comprehensive cancer center.
Authors: Fangman Benjamin David , Haff Stephen , Scielzo Shannon , Sanjeevaiah Aravind , Verma Udit N. , Cox John Vernon , Kainthla Radhika , Beg Muhammad Shaalan , Kazmi Syed Mohammad Ali
Published: May 2019

3605

Background: Ethnic disparities can impact clinical outcomes of young-onset colorectal cancer (CRC) patients. We aimed to determine if differences in outcomes based on ethnicity exist in young–onset CRC treated at an NCI-designated comprehensive cancer center program. Methods: A retrospective chart review for stage II – IV young-onset CRC patients ≤45 years old diagnosed between 04/2011 and 11/2015. Patients had to undergo treatment at safety-net Parkland Hospital (PH) or at the Simmons Comprehensive Cancer Center (SCCC) in Dallas, TX. Demographic data, dates of surgery, adjuvant chemotherapy, recurrence or death were obtained. Results: Of 123 patients that met inclusion criteria, 15 were excluded due to incomplete information. Of the remaining 108 patients, 36 (33%) and 72 patients (67%) were treated at SCCC and PH, respectively. Sixty (55%) were non-Hispanic vs 48 (44.4%) Hispanic. There were more Stage IV patients at SCCC vs Parkland (58.3% vs 30.6%, p < 0.01) but there was no difference regarding ethnicity. Also, no significant difference was seen between non-Hispanic White (NHW), Hispanic, and Black patients in median days to colectomy (1 vs 13 vs 0; p = .402) or adjuvant chemotherapy (55.5 vs 53.0 vs 64.0 days, p = .820). Hispanic patients had significantly better overall survival (OS) than Black or NHW patients (p = 0.025). The OS benefit was driven by improved 5-year OS in stage II/III Hispanic vs NHW vs Black patients (95% vs 62% vs 60%; p = 0.06). Multivariate Cox Regression analysis showed stage II/III (p < 0.001) and Hispanic ethnicity (p < 0.001) were independently associated with improved outcomes. Conclusions: In young-onset CRC treated at an NCI-designated comprehensive cancer center, Hispanic ethnicity had better OS than other ethnicities and this was largely due to better outcomes in stage II and III CRC. The causes for these ethnic differences in young-onset CRC patients needs further exploration. [Table: see text]
The genomic landscape and its prognostic significance for stage III colorectal cancer in Japan: An ancillary study of JCOG0910 trial—JCOG1506A1.
Authors: Shida Dai , Kuchiba Aya , Shibata Tatsuhiro , Hamaguchi Tetsuya , Yamasaki Satoshi , Ito Masaaki , Kobatake Takaya , Takiguchi Nobuhiro , Masaki Tadahiko , Shiozawa Manabu , Takii Yasumasa , Uetake Hiroyuki , Okamura Shu , Ojima Hitoshi , Nishizawa Yusuke , Takeyama Hiroshi , Kanato Keisuke , Shimada Yasuhiro , Murakami Yoshinori , Kanemitsu Yukihide ,   Colorectal Cancer Study Group of Japan Clinical Oncology Group
Published: May 2019

3607

Background: To date, large-scale genomic sequencings of colorectal cancers (CRC) have been reported mainly from Western countries. However, ethnic diversities, differences by stage, and the prognostic impact of the genomic landscape in CRC remain poorly identified. Methods: The subjects were 534 patients (pts) with stage III CRC from the JCOG0910 study—a randomized phase-III trial conducted in Japan on 1564 pts to assess the efficacy of S-1 versus capecitabine as adjuvant chemotherapy. Targeted-capture sequencing of 171 potentially CRC-associated genes was performed on both normal tissue and tumor samples, and somatic single-nucleotide variants and insertion/deletions were determined. Tumors with MSIsensor scores > 7 and ultra-mutated tumors with POLE mutations were grouped as hypermutated tumors. Genes whose alterations were associated with recurrence-free survival (RFS) were evaluated using multivariable Cox regression models. Results: Of the 534 pts (right-sided: 184, left-sided: 350), 109 pts had recurrences or died during the study. Mutation frequencies were as follows: TP53, 75.3%; APC, 75.1%; KRAS, 43.6%; PIK3CA, 19.7%; FBXW7, 18.5%; SOX9, 11.8%; COL6A3, 8.2%; NOTCH3, 4.5%; NRAS, 4.1%; and RNF43, 3.7%. Thirty-one tumors were hypermutated (5.8%) (right: 14.1%, left: 1.4%). None of the 49 genes with mutation frequencies > 3% showed a significant association with RFS based on Bonferroni’s adjustment for multiple testing. The following modest associations were observed: mutant KRAS [HR, 1.66; p=0.011] and mutant RNF43 [HR, 2.17; p=0.055] had poorer RFS, whereas mutant COL6A3 [HR, 0.35; p=0.040] and mutant NOTCH3 [HR, 0.18; p=0.093] had better RFS. RFS tended to be better for hypermutated than for non-hypermutated tumors [HR, 0.53; p=0.229]. Conclusions: The overall mutation spectrum of our stage III CRC cohort was generally similar to that of the Cancer Genome Atlas (TCGA). However, the mutation frequencies of TP53, SOX9, and FBXW7 were higher, and the proportion of hypermutated tumors was lower. Multiple gene mutations seemed to impact RFS, indicating that tumor genomic profiling has a high potential to support precision medicine for pts with CRC.
Preoperative chemosensitivity testing as predictor of treatment benefit in adjuvant stage III colon cancer: Preliminary analysis of the PePiTA study.
Authors: Hendlisz Alain , Caparica Rafael , Deleporte Amélie , Van Laethem Jean-Luc , Vergauwe Philippe , Van Den Eynde Marc , Deboever Guido , Janssens Jozef , Demolin Gauthier , Holbrechts Stephane , Clausse Marylene , De Grez Thierry , Vermeij Joanna , D'Hondt Lionel A. , Geboes Karen Paula , Besse-Hammer Tatiana , Buggenhout Alexis , Paesmans Marianne , Piccart Martine , Flamen Patrick
Published: May 2019

3610

Background: Although being the standard-of-care for stage III colon cancer, no biomarkers can identify patients (pts) who benefit from adjuvant chemotherapy. In metastatic pts, the lack of metabolic response (mR) in FDG-PET/CT after 1 chemotherapy cycle predicts the absence of treatment benefit. The PePiTA study aims to evaluate if the absence of mR after 1 cycle of pre-operative chemotherapy is predictive of recurrence in non-metastatic colon cancer pts. Herein, we report a preliminary analysis on surgical outcomes, adverse events and mR assessment after 1 cycle of pre-operative chemotherapy after completing the study accrual objective. Methods: Colon cancer pts eligible for curative resection and ECOG ≤1 received 1 cycle of mFOLFOX followed by surgery in this prospective, multicentre, non-randomized trial. FDG-PET/CT was performed at baseline and after 1 cycle of mFOLFOX. Adjuvant mFOLFOX was administered for up to 12 cycles for stage III pts, whereas for stage II pts the decision to pursue adjuvant chemotherapy was at investigator’s discretion. A decrease ≥15% in SUVmax after 1 cycle of chemotherapy was defined as mR (EORTC criteria) at central review. Results: mR was assessable on the primary tumor in 204/240 pts (85%). In 11 pts (4.6%), staging was modified by the baseline FDG-PET/CT, which detected metastatic disease or other tumors. Pre-operative mFOLFOX was administered to 218 pts, of which 14 (6%) had a grade ≥3 adverse event. Surgery was performed in 218 pts, with a median delay of 20 days (6 to 59) after chemotherapy. Surgical complications occurred in 28 (13%) pts, however no deaths occurred. The median SUVmax decrease between baseline and 2nd FDG-PET/CT was 24%. A mR was observed in 65.2% of the pts, whereas 34.8% showed no mR, including 3% who had progressive disease. Conclusions: One cycle of pre-operative mFOLFOX followed by a mR assessment has shown to be a feasible and safe strategy, raising interest on the potential of neoadjuvant chemotherapy in colon cancer. The early mR assessment identified pts that may not benefit from chemotherapy and might have a worse prognosis. The substantiation of this hypothesis is expected with the study’s long-term results. Clinical trial information: NCT00994864.
Clinical features and survival among patients with standard-onset versus early-onset colorectal cancer by age groups.
Authors: Acuna Villaorduna Ana , Shah Nishi , Goel Sanjay
Published: May 2019

3614

Background: Colorectal cancer (CRC) incidence is increasing in patients younger than 50 years old. Currently, there are discordant recommendations regarding CRC screening: while the American Cancer Society favors to start at age 45, the National Comprehensive Cancer Network and the US Preventive Task Force suggest starting at age 50. This study is aimed to compare the incidence, clinical characteristics and survival of patients diagnosed with standard-onset CRC (SO) versus early-onset colorectal cancer by age-groups. Methods: Patients diagnosed with CRC at ages older than 35 were identified using the SEER registry and categorized into four groups based on age at diagnosis. EO1 (35-39), EO2 (40-44), EO3 (45-49) and SO (>50) years, respectively. Incidence, clinical features and survival were compared among groups. Results: 178 678 patients were identified. 9.2% were diagnosed before 50 years. Of these, 1.4%, 2.8% and 5.1% were EO1, EO2 and EO3; respectively. Patients with early-onset CRC (EO) had higher frequency of Hispanics (13.9% vs. 8.4%, p<0.01), stage IV (24.8% vs. 17.3%, p<0.01), left-sided tumors (74.1% vs. 56.9%, p<0.01) and better survival compared to SO. Among EO groups, the frequency of poor/anaplastic grade was inversely proportional to age; stage IV was similar between EO2 and EO3 and lower in EO1. Black race, grade and stage were predictors of mortality for all EO groups; laterality was a mortality predictor in EO2 and EO3. Conclusions: EO-CRC and SO-CRC have different pathological features that should be considered for CRC screening. Higher rates of stage IV disease are encountered in patients between 40-49 years old; hence early screening should be considered. Given higher rates of left-sided tumors, sigmoidoscopy might be an adequate tool for most patients with EO-CRC. [Table: see text]
APACT: phase III, multicenter, international, open-label, randomized trial of adjuvant nab-paclitaxel plus gemcitabine (nab-P/G) vs gemcitabine (G) for surgically resected pancreatic adenocarcinoma.
Authors: Tempero Margaret A. , Reni Michele , Riess Hanno , Pelzer Uwe , O'Reilly Eileen Mary , Winter Jordan Michael , Oh Do-Youn , Li Chung-Pin , Tortora Giampaolo , Chang Heung-Moon , Lopez Charles D. , Tabernero Josep , Van Cutsem Eric , Philip Philip Agop , Goldstein David , Berlin Jordan , Ferrara Stefano , Li Mingyu , Lu Brian D. , Biankin Andrew
Published: May 2019

4000

Background: In metastatic pancreatic cancer (PC), nab-P/G demonstrated significantly longer overall survival (OS) vs G. APACT assessed efficacy & safety of nab-P/G vs G in surgically resected PC. Methods: Treatment (tx)-naive patients (pts) with histologically confirmed PC, macroscopic complete resection, ECOG PS 0/1, & CA19-9 < 100 U/mL were eligible. Stratification factors: resection status (R0/R1), lymph node status (LN+/−), & geographic region. Tx was initiated ≤ 12 wks postsurgery. Pts received nab-P 125 mg/m2 + G 1000 mg/m2 or G 1000 mg/m2 on days 1, 8, 15 of six 28-day cycles. Primary endpoint was disease-free survival (DFS) by independent reviewer (IR); IRs received baseline clinical data & scans. Secondary endpoints were OS & safety. ≈438 DFS events were needed for 90% power to detect an HR for disease recurrence or death of 0.73 with nab-P/G vs G at a 2-sided significance level of 0.05. Results: 866 pts were randomized. Median age was 64 y (range, 34 - 86); most pts had ECOG PS 0 (60%), LN+ (72%), & R0 (76%). 69% of pts completed 6 tx cycles ( nab-P/G, 66%; G, 71%). Median follow up for OS was 38.5 mo. Median IR-assessed DFS (439 events) was 19.4 mo ( nab-P/G) vs 18.8 mo (G) (HR, 0.88; 95% CI, 0.729 - 1.063; stratified log-rank P = 0.1824). Investigator-assessed DFS (571 events) was 16.6 mo ( nab-P/G) vs 13.7 mo (G) (HR, 0.82; 95% CI, 0.694 - 0.965; nominal P = 0.0168). Interim OS (427 events) was 40.5 mo ( nab-P/G) vs 36.2 mo (G) (HR, 0.82; 95% CI, 0.680 - 0.996; nominal P = 0.045). Grade ≥ 3 TEAEs were reported in 86% vs 68% of pts with nab-P/G vs G. The most common grade ≥ 3 hematologic & nonhematologic TEAEs with nab-P/G vs G were neutropenia (49% vs 43%) & fatigue (10% vs 3%). TEAEs led to death in 2 pts in each arm. Conclusions: IR DFS with nab-P/G was not significantly longer vs G; median DFS with G was longer than historical data. DFS by investigator (sensitivity analysis) and interim OS were improved with nab-P/G vs G (HR 0.82 for both). Adjuvant nab-P/G may be an option for pts who are ineligible for FOLFIRINOX. Additional OS follow-up may better support nab-P/G as an option in the adjuvant setting. Clinical trial information: NCT01964430.
A multicenter randomized controlled trial to evaluate the efficacy of surgery vs. radiofrequency ablation for small hepatocellular carcinoma (SURF trial).
Authors: Izumi Namiki , Hasegawa Kiyoshi , Nishioka Yujiro , Takayama Tadatoshi , Yamanaka Naoki , Kudo Masatoshi , Shimada Mitsuo , Inomata Masahumi , Kaneko Shuichi , Baba Hideo , Koike Kazuhiko , Omata Masao , Makuuchi Masatoshi , Matsuyama Yutaka , Kokudo Norihiro
Published: May 2019

4002

Background: Surgery (SUR) and radiofrequency ablation (RFA) are both known to be effective therapy for treating patients with small oligonodular hepatocellular carcinoma (HCC), however there is only insufficient evidence about which therapy is more preferred approach. This randomized controlled trial was designed to prospectively compare the efficacy of SUR and RFA as the first approach to primary HCC. Methods: In this open-label trial undertaken at 49 hospital in Japan, we recruited patients having primary HCC with tumor foci numbering less than 3, each measuring 3 cm or less, Child-Pugh score of 7 or less, ages between 20 and 79 year. Before randomization, technical and liver functional feasibility for both treatment arms were confirmed by joint chart review by surgeons and hepatologists. Patients were then randomly assigned in a 1:1 ratio to undergo SUR or RFA, stratified by age, infection of hepatitis-C virus, number of tumors, tumor size and institution. The primary endpoint was recurrence free survival (RFS) and overall survival (OS). Results: Between April 2009 and August 2015, total 308 patients were enrolled to this trial. Because of ineligibility 15 patients were excluded, therefore 145 patients underwent SUR and 148 patients underwent RFA finally. There was no perioperative mortality. Under the median follow-up of 5 years, the 3-year RFS of patients underwent SUR and RFA was 49.8%, 47.7%, respectively (hazard ration [HR] 0.96, 95% CI 0.72-1.28; p = 0.793). OS will be analyzed and published after two years. Conclusions: SUR and RFA were both safe therapeutic approaches and provided equally RFS for early stage HCC smaller than 3 cm. Clinical trial information: UMIN000001795.
Results of KEYNOTE-240: phase 3 study of pembrolizumab (Pembro) vs best supportive care (BSC) for second line therapy in advanced hepatocellular carcinoma (HCC).
Authors: Finn Richard S. , Ryoo Baek-Yeol , Merle Philippe , Kudo Masatoshi , Bouattour Mohamed , Lim Ho-Yeong , Breder Valeriy Vladimirovich , Edeline Julien , Chao Yee , Ogasawara Sadahisa , Yau Thomas , Garrido Marcelo , Chan Stephen Lam , Knox Jennifer J. , Daniele Bruno , Ebbinghaus Scot , Chen Erluo , Siegel Abby B. , Zhu Andrew X. , Cheng Ann-Lii ,   for the KEYNOTE-240 Investigators
Published: May 2019

4004

Background: Pembro received accelerated approval based on results of KEYNOTE-224, a phase 2 trial in pts with advanced HCC in the second line setting. KEYNOTE-240 (NCT02702401) was a randomized, placebo (Pbo) controlled, phase 3 study of Pembro vs BSC in pts with previously treated advanced HCC. Methods: Eligible pts had a radiographic or pathologic diagnosis of HCC, radiographic progression on/intolerance to sorafenib, Child-Pugh A disease and ECOG PS 0-1. Pts were randomized 2:1 to receive Pembro 200 mg + BSC or Pbo + BSC IV every 3 wk, stratified by geographic region, macrovascular invasion and ɑ-fetoprotein levels for ≤35 cycles or until confirmed PD/unacceptable toxicity. Response was assessed every 6 wk per RECIST v1.1 by central imaging review. Co-primary endpoints were OS and PFS. Secondary endpoints included ORR, DOR and safety. Data cutoff was Jan 2 2019 for OS; Mar 26 2018 for PFS and ORR. Results: 413 patients were randomized; 278 to Pembro and 135 to Pbo. After a median follow up of 13.8 mo, 10.1% of pts remained on Pembro and 3.0% on Pbo. Pembro improved OS (HR: 0.78; one sided p = 0.0238) and PFS (HR: 0.78; one sided p = 0.0209) vs Pbo; these differences did not meet significance per the prespecified statistical plan. ORR was 16.9% (95% CI 12.7-21.8%) for Pembro vs 2.2% (95% CI 0.5-6.4%) for Pbo (nominal one sided p = 0.00001); responses on Pembro were durable (median DOR: 13.8 mo [1.5-23.6+]). Off study, new therapy use was 42% for Pembro and 47% for Pbo. The safety profile including incidence of hepatitis and other immune mediated events was generally consistent with that previously reported in Pembro studies; no cases of HBV/HCV flare were identified. Conclusions: Pembro reduced the risk of death by 22% and improved PFS over Pbo in pts with advanced HCC, although significance was not reached per prespecified statistical criteria. ORR in the Pembro arm was consistent with that of KEYNOTE-224. Subsequent anticancer therapy in the Pbo arm likely impacted the OS results. The safety profile was comparable to that established for Pembro monotherapy. These results are overall consistent with those of KEYNOTE-224 further supporting second line therapy with Pembro in HCC pts. Clinical trial information: NCT02702401.
Pembrolizumab versus chemotherapy as second-line therapy for advanced esophageal cancer: Phase 3 KEYNOTE-181 study.
Authors: Shah Manish A. , Adenis Antoine , Enzinger Peter C. , Kojima Takashi , Muro Kei , Bennouna Jaafar , Francois Eric , Hsu Chih-Hung , Moriwaki Toshikazu , Kim Sung-Bae , Lee Se-Hoon , Kato Ken , Shen Lin , Qin Shukui , Ferreira Paula , Wang Ruixue , Bhagia Pooja , Kang S. Peter , Metges Jean-Philippe , Doi Toshihiko
Published: May 2019

4010

Background: The phase 3 KEYNOTE-181 study compared pembrolizumab (pembro) vs chemo as second-line therapy for patients (pts) with advanced/metastatic squamous cell carcinoma (SCC) and adenocarcinoma (ACC) of the esophagus (NCT02564263). Methods: Eligible pts were randomized 1:1 to pembro 200 mg Q3W for up to 2 years or choice of paclitaxel, docetaxel, or irinotecan. Randomization was stratified by histology (SCC vs adenocarcinoma) and region (Asia vs rest of world). Primary end points were OS in the SCC, PD-L1 combined positive score (CPS) ≥10, and the ITT. Secondary endpoints included PFS, ORR, safety; exploratory endpoints included health-related quality of life (HRQoL) in CPS ≥10. Results: 628 pts were randomized (401 with SCC; 222 with CPS ≥10). As of Oct. 15, 2018, median follow-up was 7.1 mo (pembro) vs 6.9 mo (chemo). In CPS ≥10, OS was superior with pembro vs chemo (median 9.3 vs 6.7 mo; HR 0.69; 95% CI 0.52-0.93; P= 0.0074). In CPS ≥10 SCC, median OS was 10.3 mo vs 6.7 mo and in CPS ≥10 ACC, median OS was 6.3 mo vs 6.9 mo; 12-mo OS rates were higher with pembro vs chemo (Table). In SCC, median OS was 8.2 mo vs 7.1 mo; HR 0.78; 95% CI 0.63-0.96; P= 0.0095. In the ITT, median OS was 7.1 mo vs 7.1 mo; HR 0.89; 95% CI 0.75-1.05; P= 0.0560. Updated OS will be presented. Grade 3-5 drug-related AEs (≥10% incidence in either arm) included decreased white blood cells (0% vs 10%), decreased neutrophils (0.3% vs 10%). In CPS ≥10, HRQoL improved with pembro vs chemo only for EQ-5D VAS (difference in LS mean change from baseline 5.57; 95% CI 0.58-10.56). Conclusions: Pembro significantly improved OS vs chemo as second-line therapy for advanced esophageal cancer with PD-L1 CPS ≥10, with a more favorable safety profile and stable and similar QOL. These data support pembro as a new second-line standard of care for esophageal cancer with PD-L1 CPS ≥10. Clinical trial information: NCT02564263. [Table: see text]
Impact of age and sex on chemotherapy (CTx) efficacy, toxicity and survival in early oesophagogastric (OG) cancer: A pooled analysis of 3265 patients from four large randomised trials (OE02, OE05, MAGIC & ST03).
Authors: Athauda Avani , Nankivell Matthew Guy , Langley Ruth E , Alderson Derek , Allum William H. , Grabsch Heike I , Chau Ian , Starling Naureen , Falk Stephen , Crellin Adrian , Mansoor Wasat , Coxon Fareeda , Darby Suzanne , Thompson Joyce , Cummins Sebastian J. , Beaumont Erica , West Nicholas , Langer Rupert , Pritchard Susan , Cunningham David
Published: May 2019

4022

Background: No large scale randomised data exists evaluating the impact of age and sex in patients (pts) undergoing potentially curative surgery and CTx for OG cancer. However, differences in age and sex may be contributing factors to variability in CTx dose-response and toxicity which could also impact survival. Methods: Data from four prospective randomised controlled trials were pooled using a two-stage meta-analysis. For survival data, hazard ratios were calculated for pts <70 and ≥70 years and between males and females. Pts were allocated to receive neoadjuvant platinum and fluoropyrimidine +/- anthracycline and bevacizumab. Mandard tumour regression grade (TRG) and prevalence of ≥G3 toxicities were compared according to the same subgroups using Chi-squared test. Results: 3265 pts were included for survival analysis (2668 (82%) M, 597 (18%) F; 2626 (80%) <70, 639 (20%) ≥70). A significant improvement in disease specific survival (DSS) (HR 0.78; p<0.001) and OS (HR 0.78; p<0.001) was observed in females vs males. Although OS was worse in older vs younger pts (HR 1.15; p=0.01) no significant difference in DSS was observed (HR 1.04; p=0.52). For those pts who underwent resection following neoadjuvant CTx, older patients (19 vs 13%; p=0.01) and female patients (19% vs 13%, p=0.02) were more likely to achieve more favourable Mandard TRG 1&2 scores. Older pts experienced significantly more ≥G3 neutropaenia (30 vs 22%; p=0.004). Females experienced significantly more ≥G3 nausea (12 vs 7%; p=0.006), vomiting (10 vs 5%; p≤0.001) and diarrhoea (9 vs 4%; p=0.001). Conclusions: This study represents the largest pooled analysis of age and sex differences on safety of neoadjuvant CTx and survival in early OG cancer. Females had significantly improved survival while experiencing more GI toxicities. Older pts achieved comparable DSS and thus, dependent on fitness, should be offered the same treatment paradigm as younger pts.
Tumor mutation burden and immunogenicity in gastric cancer with HER2 alterations.
Authors: Wei Bo , Xing Xiaojing , Li Ziyu , Han Quanli , Hao Yingxue , Zhou Jing , Zhang Yuzi , Zhao Jing , Cai Shangli , Gu Yanhong , Chen Tufeng
Published: May 2019

4024

Background: Human epidermal growth receptor 2 (HER2) is considered as an oncogenic driver gene in gastric cancer (GC). Immunotherapy has been proven to be effective in GC patients. Previous studies indicated that patients harboring driver mutations were considered as poor candidate for immunotherapy. But the efficacy of immunotherapy for HER2 positive GC has not been defined. We therefore analyzed the immunogenicity of HER2 alterations in GC. Methods: Genomic profiling of DNA from 448 GC was performed using next-generation sequencing on 381 cancer associated genes. The expression of PD-L1 protein was evaluated in 192 GC with the use of an automated immunohistochemical assay (Ventana, SP263). Whole-exome sequencing, copy number variations, RNA-seq and clinical data of 443 GC from The Cancer Genome Altas (TCGA) were also analyzed to further evaluate the immunogenicity of HER2 alterations. TMB was defined as number of somatic non-synonymous mutations in coding regions. HER2 amplification in TCGA was defined as “2” derived from the copy-number analysis algorithms GISTIC. Results: HER2 alterations including amplification, missense and fusion were present in 19.2% (85/443) of TCGA cohort and 11.4% (51/448) of clinical cohort. 14.0% (62/443) of TCGA cohort and 6.0% (27/448) of clinical cohort harbored HER2 amplification. Higher TMB was observed in MSS/MSI-L patients carrying any HER2 alterations in TCGA cohort (P = 0.009). On the contrary, HER2 alterations did not show a higher neoantigen level and HER2 alterations were associated with decreased immunogenicity in terms of immune-related gene mRNA expression and immune infiltrates. In clinical cohort, HER2 alterations was also significantly associated with higher TMB (P = 0.001). Meanwhile, a trend of shrinking proportion of PD-L1 expression was observed in HER2 alteration subgroup (2/23, 8.7%) than HER2 wild-type subgroup (47/169, 27.8%, P = 0.071). Furthermore, HER2 amplification had significant positive associations with HRD score (P = 0.0169) in TCGA cohort which indicated an increased degree of genome instability. Conclusions: Although HER2 alterations in GC were associated with increased TMB, HER2 alterations exhibited poor immunogenicity. These findings indicated that HER2 alterations might confer resistance to immune monotherapy.
A phase II study of S-1, oxaliplatin, and nab-paclitaxel, and itraconazole aimed at conversion surgery for advanced and recurrent gastric cancer.
Authors: Nakamoto Yoshihiko , Tsubamoto Hiroshi , Sawazaki Miyuki , Kakuno Ayako , Sonoda Takashi
Published: May 2019

4026

Background: Preclinical and clinical studies demonstrated that itraconazole, a common anti-fungal agent, has anticancer activity. The purpose of this study was to evaluate the efficacy of the chemotherapy with itraconazole on unresectable, metastatic, and recurrent gastric cancer. Methods: All patients were referred to our clinic with a clinical diagnosis of unresectable gastric cancer. The regimen consisted of 160 mg/m2 nab-paclitaxel IV on day 1, 100 mg/m2 oxaliplatin IV on day 1, 60 mg/m2 S-1 orally on days 1-7, and 400mg itraconazole orally on days -1 to 3, repeated every 3 weeks. Conversion surgery was allowed. The primary endpoint was overall survival (OS). Results: Between 2015 and 2018. 23 patients were enrolled. Their median age was 68 years (range 40-80 years); stomach/gastroesophageal junction: 21/2; Stage IIIA/IIIB/IV: 2/1/20. Among 10 patients who had liver metastases, 2 had simultaneous lung metastases. Nine patients had peritoneal dissemination. Five patients with stage IV had recurrent disease after primary surgery followed by adjuvant S-1. The other 18 patients had no history of surgery or chemotherapy. Response rate was 70% (CR/PR: 2/14). Among 12 patients (67%) who had conversion surgery, R0 resection was conducted in 8 and no residual tumor was observed in 2. Among enrolled 23 patients, median OS was 22 months (95%CI: > 12 months) and 1-year OS rate was 81.8% (95%CI: 46.7%―95.5%). Grade 3/4 neutropenia in 5 (22%), no grade 3/4 thorombocytopenia, grade 2 peripheral sensory neuropathy in 6 (26%). Conclusions: The addition of itraconazole to chemotherapy showed promising efficacy with high conversion surgery rate and with acceptable toxicities. Clinical trial information: UMIN000021340.
Pembrolizumab in previously treated metastatic esophageal cancer: Longer term follow-up from the phase 2 KEYNOTE-180 Study.
Authors: Kato Ken , Kojima Takashi , Hochhauser Daniel , Bennouna Jaafar , Hollebecque Antoine , Lordick Florian , Kim Sung-Bae , Tajika Masahiro , Kim Heung Tae , Park Haeseong , Saba Nabil F. , Urba Susan , Desai Anjali , Liu Qi , Cruz Sandra , Shah Manish A.
Published: May 2019

4032

Background: In the phase 2, open-label, KEYNOTE-180 (NCT02559687) study, after a median follow-up of 5.8 months, pembrolizumab (pembro) provided antitumor activity with durable responses in pts with previously treated, advanced/metastatic adenocarcinoma (EAC) including Siewert type 1 adenocarcinoma of the gastroesophageal junction or squamous cell carcinoma (ESCC) of the esophagus. Here we present results of an additional 10 months of follow-up. Methods: Eligible pts with metastatic esophageal cancer, ≥2 prior lines of therapy, and tumor samples evaluable for biomarker expression, received pembro 200 mg Q3W for up to 2 years, or until disease progression, unacceptable toxicity, or withdrawal. Tumor response was assessed Q9W (RECISTv1.1, central review). PD-L1+ pts had combined positive score ≥10 using IHC (22C3 antibody). Primary endpoint was objective response rate (ORR). Secondary endpoints included safety, DOR, PFS, and OS. Results: Of 121 pts enrolled, 63 (52%) had ESCC and 58 (48%) had PD-L1+ (combined positive score ≥10) tumors. As of July 30, 2018, median follow-up duration, from randomization to data cutoff, was 5.8 mo (range, 0.2 mo to 27.8+ mo). ORR (CR+PR) was 10% (95% CI, 5%-17%); 2 (2%) CR,10 (8%) PR, 25 (21%) SD. Median DOR was not reached ([NR] range, 2.1 mo to 25.1+ mo). Median PFS was 2 mo (95% CI, 1.9%-2.1%) with 9-mo PFS rate of 9%. Median OS was 5.8 mo (4.5-7.2) with 12 mo OS rate of 27%. In ESCC, ORR was 14% (95% CI, 7%-25%); 2 (3%) CR, 7 (11%) PR, with median DOR NR (range, 4.2 mo to 25.1+ mo). In EAC, ORR was 5% (95% CI, 1-14); 3 PR, with median DOR NR (range, 2.1 mo to 15.6+ mo). In PD-L1+ pts, ORR was 14% (95% CI, 6%-25%); 1 (2%) CR, 7 (12%) PR with median DOR NR (range, 4.2 mo to 25.1+ mo). In PD-L1- pts ORR was 6% (95% CI, 2%-16%); 1 (2%) CR, 3 (5%) PR; median DOR NR (range, 2.1 mo to 17.3+ mo). Overall, 19 (16%) pts had treatment-related grade 3-5 AEs. Seven (6%) pts discontinued due to a treatment-related AE. There was one treatment-related death from pneumonitis. Conclusions: Pembro continued to provide durable clinical benefit with a manageable safety profile for pts with heavily pretreated esophageal cancer, with conversions of PR to CR observed. Clinical trial information: NCT02559687.
Trifluridine/tipiracil (FTD/TPI) in patients (pts) aged ≥65 years with metastatic gastric/gastroesophageal junction cancer (mGC/mGEJC): Subgroup analysis from TAGS.
Authors: Shitara Kohei , Doi Toshihiko , Hosaka Hisashi , Thuss-Patience Peter C. , Santoro Armando , Jiménez-Fonseca Paula , Longo Federico , Ozyilkan Ozgur , Cicin Irfan , Park David , Tejani Mohamedtaki Abdulaziz , Zaanan Aziz , Bilancia Domenico , Pericay Carles , Ozguroglu Mustafa , ALSINA MARIA , Makris Lukas , McGuigan Sandra , Ilson David H.
Published: May 2019

4037

Background: 60% of newly diagnosed GC pts are > 65 y of age, a proportion that is increasing. The global phase 3 study TAGS (NCT02500043) demonstrated the efficacy and safety of FTD/TPI in previously treated pts with mGC/mGEJC. Here we report results in the pt subgroup aged ≥65 in TAGS. Methods: Pts with mGC/mGEJC treated with ≥2 prior chemotherapy regimens were randomized (2:1) to receive FTD/TPI (35 mg/m2 BID on days 1–5 and 8–12 of each 28-day cycle) or placebo, plus best supportive care. A preplanned efficacy/safety analysis was performed in pts aged ≥65 y. Results: Of 507 randomized pts, 228 (45%) were aged ≥65 y (range 65–89). The pt subset aged ≥65 y was similar to the overall population, except for a higher incidence of moderate renal impairment in the elderly subgroup (31% vs 17%). For pts aged ≥65 y, baseline characteristics were generally balanced across the treatment groups, although more pts treated with FTD/TPI than with placebo had ECOG PS 1 (69% vs 59%). FTD/TPI had an efficacy benefit in pts aged ≥65 y, and the FTD/TPI safety profile was similar in this subgroup vs the overall population (table). Treatment-related deaths (one in each treatment group) did not occur in pts aged ≥65 y. No drug-related deaths associated with cardiotoxicity were reported in pts aged ≥65 y. Although dose modifications were used more often in this subgroup, there was no increase in discontinuations vs the overall population. Conclusions: FTD/TPI was safe and effective in pts aged ≥65 y, who had a higher incidence of moderate renal impairment vs the overall population. Clinical trial information: NCT02500043. [Table: see text]
Recurrence risk evaluation in stage IB gastric cancer with TP53 codon 72 polymorphism.
Authors: Nishizuka Satoshi , Ohmori Yukimi , Iwaya Takeshi , Koeda Keisuke ,   The Northern Japan Gastric Cancer Study Consortium
Published: May 2019

4044

Background: Post-operative adjuvant chemotherapy is not currently indicated for Stage IB gastric cancer. However, about 10% of these patients experience recurrence and metastasis. Our previous study on a panel of gastric cancer cell lines indicated that TP53 codon 72 polymorphisms may affect the degree of biological malignancy. Hence, we hypothesized that the TP53 codon 72 polymorphisms may have been associated with post-operative survival without adjuvant chemotherapy. In this study, we investigated the risk of recurrence after treatment of Stage IB gastric cancer patients carrying the TP53 codon 72 polymorphism and attempted to identify a subpopulation that should receive post-operative adjuvant chemotherapy. Methods: Among 658 gastric cancer patients who received gastrectomy with curative-intent, 130 Stage IB patients were enrolled in the present study. The TP53 codon 72 polymorphisms of formalin-fixed paraffin-embedded cancer tissue sections were assessed by direct sequencing using originally designed primers. Overall survival rate (OS) and relapse-free survival rate (RFS) were analyzed based on the status of TP53 codon 72 polymorphism "Arg/Arg", "Arg/Pro" and "Pro/Pro". The hazard ratio for each subgroup was compared by TP53 codon 72 polymorphism. All interaction p values were calculated using the likelihood test. Results: Of the 125 patients for whom polymorphism analysis results were available, the 5- and 10-year OS was 84.5% and 63.9%, respectively. The 5- and 10-year RFS was 82.2% and 64.3%, respectively. When the study cohort was divided into two groups according to polymorphism status (i.e., Arg/Arg and Arg/Pro vs. Pro/Pro), both the OS (hazard ratio [HR], 1.968; 95% confidence interval [CI], 0.770-7.430, p = 0.045) and RFS (HR, 1.976; 95% CI, 0.778-7.515, p = 0.033) of the Pro/Pro group across the entire observation period were significantly lower than those for the Arg/Arg and Arg/Pro group. The majority of recurrences in Pro/Pro occurred within three years from the operation. Conclusions: Among Stage IB gastric cancer patients that underwent gastrectomy with curative-intent, post-operative adjuvant chemotherapy may be considered immediately after surgery for patients carrying the TP53 codon 72 Pro/Pro polymorphism.
Total neoadjuvant chemo (ctx; TNT) for locally advanced gastric cancer (GC): The Memorial Sloan Kettering Cancer Center experience.
Authors: Greally Megan , Strong Vivian E. , Yoon Sam S. , Coit Daniel G. , Chou Joanne F , Capanu Marinela , Kelsen David Paul , Janjigian Yelena Yuriy , Ilson David H. , Ku Geoffrey Yuyat
Published: May 2019

4046

Background: Peri-op chemo (ctx) and surgery is a standard in the treatment of GC, based on the MAGIC (NEJM 2006; 355:11) and FLOT4 (J Clin Oncol 35:4004 [abstr]) studies. However, less than half of patients (pts) completed ctx in the MAGIC and FLOT4 studies, mainly from issues delivering post-op therapy. We assessed safety and feasibility of TNT, where all ctx is given pre-op. Methods: We reviewed GC pts who received TNT or peri-op ctx and had surgery; decision for TNT was by physician preference, based on clinical or radiographic benefit to justify completing ctx pre-op. Pt characteristics were compared using Fisher’s exact and Wilcoxon Rank Sum tests. Post-op length of stay (LOS) was calculated from date of surgery (DOS) to date of discharge and surgical morbidity was determined using the Clavien-Dindo classification. Progression free survival (PFS) and overall survival (OS) were calculated from DOS using Kaplan-Meier methods and compared between groups using the log-rank test. Results: 120 pts were identified, median age 63, 62.5% male, 98% ECOG 0/1. 93 pts (77.5%) received peri-op ctx and 27 (22.5%) received TNT. In peri-op pts, 19%, 43% and 38% received FLOT, platinum/fluropyrimidine (FP) and ECF/EOX respectively. In TNT pts, 56%, 37% and 7% received FLOT, platinum/FP and ECF/EOX respectively. 57% had subtotal gastrectomy. Surgical outcomes were similar between groups; median LOS was 6 and 7 days (p = 0.31) in peri-op and TNT pts respectively. There was no significant difference in Clavien Dindo grade I-II or III-IV morbidity between groups (p = 0.103). There were no deaths. TNT pts received higher proportions of planned treatment than peri-op ctx pts: 90% vs. 60% FP (0.001); 85% vs. 41% platinum ( < 0.001); 100% vs. 9% epirubicin (0.015) and 53% vs. 28% docetaxel (p = 0.169). At median follow-up of 19 months, median PFS and OS were not reached. There was no significant difference in PFS (p = 0.089) or OS (p = 0.59) between groups. Conclusions: TNT appears safe with no increase in post-op LOS or surgical morbidity observed. TNT pts had higher percentage drug delivery, suggesting potential benefit for administering all ctx before surgery. While longer survival follow-up is required, TNT may be considered in pts with locally advanced GC who are candidates for ctx.
Comparison of efficacy and safety of second-line palliative chemotherapy with paclitaxel plus raltitrexed and paclitaxel alone in patients with metastatic gastric adenocarcinoma: A randomized phase II trial.
Authors: Zhao Xiaoying , Guo Weijian , Chen Zhiyu , Zhang Xiaowei , Zhu Xiaodong , Zhang Wen , Yang Lei , Qiu Lixin , Wang Chenchen , Huang Mingzhu , Yu Hui , Li Jin , Zhang Zhe , Li Wenhua
Published: May 2019

4054

Background: Paclitaxel is a microtubule stabilizing agent that has been the standard second line chemotherapy in the treatment of advanced gastric cancer. This study was designed to find out the clinical outcome of paclitaxel plus raltitrexed regimen as second line treatment in MGC patients. Methods: In an open, randomized, multi centers phase II clinical trial , 148 patients were randomly assigned and treated with either RP (raltitrexed 3 mg/m2 d1 and paclitaxel 135mg/m2 d1,3w) or P (paclitaxel 135mg/m2 d1,3w) as second-line palliative chemotherapy. The primary endpoint is PFS, secondary endpoint is ORR, OS and safety. Results: In 148 randomly assigned and treated patients (RP = 73; P = 75), the majority of patients were males (94 vs. 54). Progression free survival has a tendency to be prolonged with RP versus P (2.7m vs. 1.7m, p = 0.148). Overall survival also has a tendency to be prolonged with RP versus P (10.2m vs. 6.1m, p = 0.140). Overall response rate was equal with RP versus P (6.8% vs.4.0%, p = 0.72). DCR in the RP group was 56.2%, P group was 36.0%. Grade 3 to 4 treatment-related adverse events occurred in 36.2% (RP) v 28.2% (P) of patients. Frequent grade 3 to 4 toxicities for RP v P were: neutropenia (11.0% v 4.0%), anemia (1.4% v 4.0%), thrombocytopenia (1.4% v 5.3%), and all grade peripheral neurotoxicity (12.3% v 17.3%),all grade elevated aminotransferase (27.4% v 14.1%). Subgroup analysis shows if the disease combined with ascites or peritoneal involved , OS of RP regimen is more longer (p = 0.05). Conclusions: Second-line palliative chemotherapy with paclitaxel plus raltitrexed provides a tendency to prolong PFS and OS, and the patients with ascites or peritoneal involved may get benifits from combined chemotherapy, which needs to be confirmed by larger sample studies. Clinical trial information: NCT02072317.
Phase I trial of hyperthermic intraperitoneal chemoperfusion (HIPEC) with cisplatin, mitomycin, and paclitaxel in patients with gastric adenocarcinoma and carcinomatosis or positive cytology.
Authors: Badgwell Brian D. , Blum Mariela A. , Ikoma Naruhiko , Wang Xuemei , Estrella Jeannelyn , Roy-Chowdhuri Sinchita , Das Prajnan , Minsky Bruce D. , Song Shumei , Mansfield Paul F. , Ajani Jaffer A.
Published: May 2019

4056

Background: This phase I trial evaluated the safety and toxicity of laparoscopic hyperthermic intraperitoneal perfusion with chemotherapy (HIPEC) combining mitomycin, cisplatin, and paclitaxel for patients with gastric cancer metastatic to the peritoneum. Methods: A Bayesian optimal interval design was used to identify the maximum tolerated dose (MTD) of escalating doses of paclitaxel (starting dose of 20 mg/m2 to maximum dose of 60 mg/m2) in combination with flat doses of mitomycin (30 mg) and cisplatin (200 mg) during laparoscopic HIPEC for patients with gastric adenocarcinoma metastatic to the peritoneum. The primary endpoint was MTD. Secondary endpoints included surgical complications and overall survival (OS). Results: A total of 27 patients were treated from November 2017 through November 2018. No dose-limiting toxicities were found. Treatment-related grade 1-2 side effects were leukopenia (11%), oral dysesthesia (4%), arthralgia (4%), and diarrhea (4%). Treatment-related grade 3-4 side effects included leukopenia (4%) and neutropenia (4%). The MTD was 60 mg/m2. Clavien-Dindo surgical complications were grade I (all representing electrolyte deficiencies requiring replacement) in 96% of patients, grade II in 4%, grade III in 0%, grade IV in 0%, and grade V in 4%. At a median follow-up of 15 months, the median OS from diagnosis of metastatic disease and the date of surgery has not been reached. One- and 2-year OS rates from the date of metastatic disease were 74% and 58%, respectively. The 1-year OS rate from the date of HIPEC was 51%. Conclusions: Laparoscopic HIPEC with mitomycin, cisplatin, and paclitaxel appears safe at intraperitoneal doses of 30 mg, 200 mg, and 60 mg/m2, respectively. Although electrolyte abnormalities are common, systemic toxicity of this therapy is modest. Survival rates are promising, supporting further research into intraperitoneal therapy for stage IV gastric cancer. Clinical trial information: NCT03330028.
Prospective evaluation of metabolic intratumoral heterogeneity using 18F-FDG-PET-CT in patients with advanced gastric cancer receiving palliative chemotherapy.
Authors: Yoo Shin Hye , Kang Seo Young , Cheon Gi Jeong , Oh Do-Youn , Bang Yung-Jue
Published: May 2019

4059

Background: Metabolic intratumoral heterogeneity (ITH) gives important information on treatment response and prognosis. However, temporal changes in metabolic ITH and their associations with treatment outcome have not been reported yet in gastric cancer (GC). We aimed to evaluate the early changes in metabolic ITH and their predictive roles in advanced GC patients receiving palliative chemotherapy. Methods: Unresectable locally advanced or metastatic GC patients were prospectively enrolled before the first-line palliative chemotherapy and underwent 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET-CT) at baseline (T1) and at the first response evaluation follow-up (T2). SUVs (Standardized uptake values), volumetric parameters, and textural features including entropyHisto and contrastGLCM were extracted from the primary gastric tumor at T1, T2, and ΔT (T2-T1) was evaluated. Associations of these parameters with treatment response, progression-free survival (PFS), and overall survival (OS) were analyzed. Results: 87 patients were analyzed. Of 86 evaluable patients, 44 obtained partial response, 33 stable disease, and 8 progressed. The objective response rate was 51.8% (95% confidence interval [CI], 40.7% to 62.7%). The median PFS and OS were 7.3 months (95% CI, 5.4 to 8.2 months) and 11.5 months (95% CI, 10.1 to 14.3 months), respectively. From T1 to T2, metabolic ITH was significantly reduced ( P < 0.01), and the degree of decrease was greater in responders than in non-responders ( P < 0.01). By multiple Cox regression analyses adjusted for clinical variables, low entropyHisto at T2 ( P= 0.001), larger decreases in coefficient of variance ( P= 0.003) and contrastGLCM ( P= 0.017) were associated with better PFS. Low SUVpeak at T2 ( P= 0.001), larger decreases in coefficient of variance ( P= 0.032) and being a responder were associated with better OS. Conclusions: Early reduction in metabolic ITH is useful to predict response to palliative chemotherapy, PFS and OS in advanced GC patients.