bluuebunny/crossref_metadata_2025 huggingface dataset:
Early outcomes in patients with locally advanced rectal cancer following total neoadjuvant therapy.
Authors: Friedrich Tyler , Goodman Karyn A. , Leong Stephen , Herter Whitney , Davis Sarah Lindsey , Vogel Jon , Gleisner Ana , Meguid Cheryl Lauren , Purcell William T. , McCarter Martin , Cowan Michelle , Schefter Tracey E. , Messersmith Wells A. , Lieu Christopher Hanyoung
Published: January 2019

848

Background: The current standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiation followed by surgery, and then adjuvant chemotherapy. An alternative approach currently being offered to patients at University of Colorado is total neoadjuvant therapy (TNT), in which patients receive all of their planned treatment, including systemic chemotherapy, preoperatively. Methods: Records of patients from the University of Colorado multidisciplinary colorectal clinic between 2/2015 and 5/2017 were retrospectively reviewed. Treatment plans for included patients involved 8 cycles of preoperative chemotherapy with FOLFOX (5-fluoruracil, oxaliplatin, leucovorin), followed by chemoradiation with concurrent capecitabine, and then resection. Patient data collected includes demographic information, initial staging, chemotherapy and radiation received, adverse effects, surgical outcomes, and clinical and pathological response to treatment. Results: At the time of our analysis, 14 patients have completed TNT and undergone surgical resection, with either abdominoperineal resection or low anterior resection (LAR), at the University of Colorado. Patients ranged in age from 39 to 74 years (mean age 56) with 8 patients (57%) female sex. All 14 patients received 5-fluorouracil with all 8 cycles, though 4 (29%) required omission of oxaliplatin by cycle 8. Toxicities from preoperative treatment were as expected, without significant delays in surgery. Of the 14 patients, 4 (29%) showed a pathologic complete response (grade 0, no residual tumor) on their surgical pathology, with 8 (57%) having either grade 0 or 1 (minimal residual tumor) response. Of the 5 patients who underwent LAR with diverting loop ileostomies, mean time to ostomy reversal was 53.6 days (range 49-61). No patients developed clinically-apparent metastatic disease during preoperative therapy. Conclusions: The use of preoperative chemotherapy in addition to standard chemoradiation for locally advanced rectal cancer is well-tolerated, results in a high rate of pathologic complete response, and allows for early reversal of diverting ileostomies.
The estrogenic hormone effect in gastric cancer.
Authors: Jang Youjin , Mok Youjae
Published: January 2019

85

Background: Estrogen receptors (ERs) are steroid hormone receptors that regulate cellular activities in many physiological and pathological processes in different tissues. A few of studies have examined the expression of ER in gastric cancer. However, considerable controversy is raised as to the expression level of ER and its prognostic value in gastric cancer. In the present study, the expression profile of ERα, ERβ was determined in gastric cancer cell lines according Lauren classification and evaluate that the treatment effect of selective estrogen receptor modulator. Methods: Using four cell lines established from human gastric carcinomas according Lauren classification, check endogenous ERα, ERβ expression levels with RT-PCR. The SERM treatment effect were detected MTT test. Using immunohistochemical detection, the present study analyzed the clinical relevance of ERα, ERβ expression in tumor cells in 197 patients who underwent curative radical surgery and who were observed on long-term follow-up. Results: Endogenous ERα was high expression not intestinal cancer cell lines but in diffuse cancer cell line. Endogenous ERβ was high expression both type cancer cell line than normal gastrointestinal cell lines. According MTT assay, only raloxifene among SERM was significant treatment effect. In immonohistochemial study of gastric tissue, ERα negative and ERβ positive was associated with good prognosis. Conclusions: ERβ may be partly involved in gastric carcinogenesis and ERβ antagonist might be new therapeutic drug for gastric cancer.
Body weight and composition changes, primary tumor side, and resection as survival predictors in metastatic colorectal cancer.
Authors: Franko Jan , Graff Tara Michelle , McClairen Christian
Published: January 2019

850

Background: Common symptoms of metastatic colorectal cancer (mCRC) are sarcopenia and weight loss. We investigated whether weight loss, sarcopenia and primary tumor resection can predict overall survival among patients (pts) with mCRC Methods: Consecutive pts newly diagnosed with mCRC in a community hospital between 2012-2014 we reviewed. We gathered initial and 6-month follow up data on weight, standardized muscle mass measure (estimated psoas muscle area/m2 height, sEPA) and subcutaneous fat (SQ). Results: There were 109 pts (age 66.9±14.5, range 37-93 years). Chemotherapy recipients were younger (n = 59, 61.2±13.3 years) and survived longer (22.3 versus 5.3 months, p < 0.001) as compared to best supportive care patients (n = 50, 73.6±13.0 years, p < 0.001). There were no baseline and 6-month differences between pts with resected versus in situ primary tumor in age (p = 0.074), baseline weight (p = 0.728) or percent weight loss (p = 0.404), albumin (p = 0.322), hemoglobin (p = 0.301), creatinine (p = 0.791), initial standardized EPA (p = 0.866), percent of sEPA loss (p = 0.952), and percent subcutaneous thickness loss (p = 0.477). Cohort was further dichotomized by median anthropometric changes at 6 months: -7.1% for weight loss, -6.2% sEPA, -3.3% SQ fat. Cox proportional hazard models demonstrated that anthropometric measures and receipt of systemic chemotherapy were the strongest predictors of survival with their predictive strength surpassing traditional predictors as age, tumor sidedness, primary tumor resection, initial BMI and serum albumin level. Conclusions: Weight loss and anthropometric changes are strongly associated with shorter survival. Prognostic characteristics of loss of weight, muscle and fat should be investigated further using more robust datasets. [Table: see text]
Clinical practice use of panitumumab combined with chemotherapy in patients with wild-type RAS metastatic colorectal cancer.
Authors: Hebart Holger Frithjof , Tomasek Jiri , Csõszi Tibor , Koukakis Reija , Kafatos George , Kuhn Anja , Björklöf Katja , Buchler Tomas
Published: January 2019

852

Background: This study aimed to understand panitumumab (pmab) use in clinical practice for patients with wild-type RAS metastatic colorectal cancer (mCRC), in first-line (1L) with FOLFOX or second-line (2L) with FOLFIRI following fluoropyrimidine-based chemotherapy (excl. irinotecan). Methods: This is a combined analysis of two observational, non-interventional prospective cohort studies conducted in Germany/France (2012-2016) and Bulgaria/Czech Republic/Hungary (2013-2016). Results: Results are presented in the order of 1L FOLFOX (n = 332) followed by 2L FOLFIRI (n = 94). Patients received a median of 10 and 11.5 pmab infusions. The median duration of pmab exposure was 5.7 and 6.9 months (note that 53 and 10 patients continued pmab use after study end). The unadjusted overall response rate (complete or partial response) was 42% and 29%, based on 45% and 44% of patients with available response data post-baseline. In the 1L setting, resectability was achieved in 9%, not achieved in 42%, and unknown in 48%. Hospitalizations were reported for 100% and 99%, mostly cancer-related visits such as scheduled anticancer treatment (e.g. chemotherapy/pmab administrations), tumor assessment visits, or interventions; 93% in both groups reported outpatient, 66% and 60% inpatient visits. Conclusions: Overall, the study results show that treatment patterns and clinical efficacy of pmab in routine clinical practice were comparable to randomized controlled trials (RCTs). The ADR/SADR skin toxicity events are lower than expected based on findings from RCTs, however, similar findings have been shown in a previous observational study. More investigation is required to understand the reason for this.[Table: see text]
Current Status of mCRC in East Europe and Middle East.
Authors: Yazici Ozan , Ucar Gokhan , Vasileia Vamvakopoulou , Turhal Serdar Nazim , Yildiz Birol , Karamouzis Michalis , Yavuz Sinan , Karadurmus Nuri , Zengin Nurullah , Abali Huseyin , Geva Ravit
Published: January 2019

853

Background: Results obtained in trials may not necessarily translate into prolonged survival of metastatic colorectal cancer (mCRC) patients (pts) in real life.This multinational registry study aimed to evaluate the real life data effecting survival of pts with mCRC. Methods: Multinational, retrospective registry study.Those mCRC pts with at least 3 year follow up data OR died before 3 year time period:diagnosis in between 2005 – 2012. Results: Totally 208 (57%) male,156 female (43%) mCRC pts were included.Median age was 62 years (min:23 max:85).Primary locations; right (n = 71, 19.5%), transvers (n = 13, 3.6%), left colon (n = 276,75%). Sites of metastasis: liver 69.7%, lung:27.4%, local relapse %12.6, peritoneum 12%, distant lymph node 10%, CNS: 1.6%. Metastasectomy (mtc) was done in 38.5%, mtc regions: liver (22.3%), lung (4.7%), other (%11.5 ). K-N RAS and BRAF wild pts were 37.4%, 16.5% and 14.3%. Aflibercept was available for %57 of pts. MSI rate was 1.6%. Most common first line chemotherapy (FLC); Oxaliplatin (O) based combination (C) 29.9%, irinotecan (İ) C with bevacizumab (bev) 16.5%, O with bev. 16.5%. Responses to FLC; CR: 8%, PR: 30.5% stable: 28.3%, progres: 24.7%. Median OS of FLC; combination with bev: 35 months (m) (95%CI, 29.1 – 40.8), anti-EGFR:38 m (95%CI, 30.1–45.8 ),only chemotherapy: 32 m (95%CI 26.3 - 37.6), p > 0.05. Second mtc was done 10.2%.Second LC was given to %66.7 of pts. İ combination with bev (24.5%) was most common SLC. Responses to SLC; CR:4.9%, PR: 15.1% , stable:13.2% progres:29.1%. Total %31.3 and 22% of pts had third and fourth LC, most common one was single agent 5-FU. Median PFS1: 10 m (95%CI 8.3 – 11.6 ), PFS2: 7 m (95%CI 6.2 –7.7 ), PFS3: 6 m (95% CI 4.6 – 7.3 ). Median OS of all pts were 35 m (95%CI 30.7 – 39.2 ). In pts with metastasectomy compared with others median OS was; 43 m (95%CI 34.4 – 51.5) vs 29 m (95% CI 25.8 vs 32.1), respectively , p: < 0.001. Median OS in right, transvers and left colon was; 25 m (95%CI, 16.6 – 33.3), 33 m (95%CI, 8.7 – 52.7), 37 m (95%CI 32.4 – 41.5), (p = 0.25). In K-N Ras wild group median PFS; anti-EGFR:13 m (95 % CI, 9.3 - 16.6) bev:13 m (95 %CI, 4.4 - 21.5), chemo:9 m (95 % CI, 6.3 - 11.6), (p: 0.3). Conclusions: The current study demonstrated median OS and prognosis of left-transvers-right colon was consistent with the phase trials.
A triplet combination with irinotecan, oxaliplatin, continuous infusion 5-fluorouracil and leucovorin (FOLFOXIRI) plus cetuximab as first-line treatment in RAS wild-type, metastatic colorectal cancer: A phase 1 dose finding study.
Authors: Kadowaki Shigenori , Masuishi Toshiki , Ura Takashi , Mitani Seiichiro , Narita Yukiya , Kato Kyoko , Honda Kazunori , Taniguchi Hiroya , Ando Masashi , Muro Kei
Published: January 2019

856

Background: The FOLFOXIRI regimen (irinotecan, oxaliplatin, 5-fluorouracil and leucovorin) improves the response rate and overall survival compared to FOLFIRI in pts with metastatic colorectal cancer (mCRC), and addition of cetuximab to chemotherapy increases efficacy in pts with RAS wild-type mCRC. We conducted a phase 1 study of FOLFOXIRI plus cetuximab to determine the maximum-tolerated dose (MTD) and recommended dose (RD) and to assess its safety and efficacy in Japanese pts with RAS wild-type mCRC. Methods: Main eligibility criteria were: histologically confirmed colorectal adenocarcinoma; KRAS and NRAS wild-type status; measurable metastatic disease according to Response Evaluation Criteria in Solid Tumors version 1.1; age 20-74 years; Eastern Cooperative Oncology Group performance status 0 or 1. Pts with UDP-glucuronosyltransferase 1A1*6/*6, *28/*28 and *6/*28 genotypes were excluded. Pts received an escalating dose of intravenous irinotecan (100, 120, and 150 mg/m2 in the dose levels 0, 1, and 2, respectively) and a fixed dose of intravenous oxaliplatin (85 mg/m2), continuous infusion 5-fluorouracil (2400 mg/m2) plus l-leucovorin (200 mg/m2), and cetuximab (an initial dose of 400 mg/m2 followed by 250 mg/m2 per week). Results: A total of 9 Japanese pts were treated (3 and 9 in the dose levels 1 and 2, respectively). No patients experienced a dose-limiting toxicity (the MTD was not reached), and the dose level 2 (irinotecan 150 mg/m2) was established as the RD. With a median 8 cycles per patient, the most common grade 3 or 4 adverse events included neutropenia (44%), paronychia (22%), and acne-like rash (11%). No febrile neutropenia and treatment-related death were observed. Among 9 pts, 1 pt had complete response, 7 pts had partial response, and 1 pt had progressive disease, for an overall response rate of 89%. As of September 24, 2017, median progression free survival was 14.0 (95% CI 7.2-20.7) months. Conclusions: The combination of cetuximab and FOLFOXIRI has shown a favorable toxicity profile and promising antitumor activity in pts with RAS wild-type mCRC. Clinical trial information: UMIN000018217.
Factors associated with efficacy of TAS-102 in patients with refractory metastatic colorectal cancer (mCRC).
Authors: Grell Peter , Dvorak Josef , Vocka Michal , John Stanislav , Tuskova Helena , Buchler Tomas , Petruzelka Lubos B. , Vyzula Rostislav , Obermannova Radka
Published: January 2019

858

Background: TAS-102 significantly improved progression free survival (PFS) and overall survival (OS) versus placebo in patients with treatment refractory mCRC. We analyzed potential predictive and prognostic factors in patients treated with TAS-102 in real-world practice. Methods: We retrospectively evaluated the clinical data of 129 patients who received TAS-102. Different factors associated with PFS and OS were analyzed. Results: Baseline characteristics were: median age 67 (range 37-83), male 63.6%, ECOG PS 0 in 40.3% and 1 in 59.7%. Primary tumor location: right 20.2%, left 79.2%, wt RAS 45%. Median number of TAS-102 treatment line 3 (range 2-8). Prior treatment: anti-EGFR 45%, anti-VEGF 83%, and regorafenib 20.9%. Median follow-up was 9.4 months. The median number of cycles of TAS-102 was 3 (range 1-14). Best achieved response was SD in 23%. Median PFS was 3.3 months and OS was 11.1 months. Any ≥ grade 3 AE was in 45%, the most common ≥ grade 3 AEs were neutropenia (40.2%), anemia (6.2%), thrombocytopenia (4.7%), febrile neutropenia (2.3%), diarrhea (1.6%), nausea (1.6%), and asthenia (1.6%). Dose reduction was needed in 29.5% and cycle delay in 53.5%. Factors significantly associated with longer PFS were: initiation of TAS-102 treatment more than 3 months from last fluoropyrimidine therapy (p = 0.022, HR 0.633), normal baseline CRP level (p = 0.004, HR 0.479), baseline WBC < 8 × 109/L (p = 0.025, HR 0.641), monocytes < 0.5 × 109/L (p = 0.016, HR 0.522), neutropenia ≥ grade 2 during treatment (p < 0.0001, HR 0.349), TAS-102 dose reduction during treatment (p < 0.0001, HR 0.397), and TAS-102 cycle delay (p < 0.0001, HR 0.402). Factors associated with longer OS were normal CRP (p = 0.001, HR 0.295), normal LDH (p = 0.006, HR 0.422), WBC < 8 × 109/L (p = 0.0001, HR 0.357), monocytes < 0.5 × 109/L (p = 0.016, HR 0.373), neutropenia ≥ G2 during treatment (p = 0.0002, HR 0.343), TAS-102 cycle delay (p = 0.002, HR 0.421), wt RAS (p = 0.05, HR 0.578). Conclusions: This analysis confirms that TAS-102 is effective in patients with refractory mCRC treated in a real-world setting. Factors associated with better outcomes were baseline CRP, WBC, monocytes, and neutropenia, dose reduction and cycle delays during the treatment.
Effect of IL-11 stimulated by co-culture with CAF on metastasis of gastric cancer cells mediated by upregulation of MUC1.
Authors: Wang Xiaoxun , Che Xiaofang , Liu Yunpeng , Qu Xiujuan
Published: January 2019

86

Background: Cancer-associated fibroblasts (CAFs), as the activated fibroblasts in tumor stroma, are important modifiers of tumor progression. However, the molecular mechanisms underlying the tumor-promoting properties of CAFs in gastric cancer remain unclear. Methods: We show that when CAFs co-cultured with gastric cancer cells, two kinds of cells produce significant amounts of interleukin-11 (IL-11). CAFs enhances the migration and invasion of gastric cancer cells through the secretion of IL-11 that activates JAK/STAT3 and MAPK/ERK pathways to upregulate MUC1 in gastric cancer cells, while deprivation of IL-11 using a neutralizing antibody or inhibition of JAK/STAT3 and MAPK/ERK pathway with specific inhibitor Stattic and PD-98059 markedly attenuates these phenotypes in gastric cancer cells induced by CAFs. Results: In this study, we find that CAFs in the tumor microenvironment promote the progression of gastric cancer through IL-11-JAK/STAT3 and MAPK/ERK signalings to upregulate MUC1. Conclusions: Taken together, these results suggest that CAFs promote the progression of gastric cancer and IL-11 targeted therapy could be a complementary approach against gastric cancer by exerting their action on stromal fibroblasts.
Effective use of electronic medical record (EMR) data in analysis of association between KRAS mutations and depression in colorectal cancer patients.
Authors: Li Jenny Jing , Harper Jessica , Zhu Hong , Bhulani Nizar , Guenther Chad Michael , Madrigales Alejandra , Gates Samantha , Kazmi Syed Mohammad Ali , Verma Udit , Toups Marisa , Beg Muhammad Shaalan
Published: January 2019

861

Background: Previous studies have demonstrated that KRAS mutations were associated with higher rates of depression in patients with metastatic colorectal cancer (CRC). The objective of this study was to evaluate the feasibility of extracting EMR data to examine the association between KRAS mutations and positive screening test for depression in CRC patients. Methods: Retrospective review of stage I to IV CRC patients seen between 2011 and 2015 at an academic, NCI-Designated Comprehensive Cancer Center was performed. At each clinic visit, depression was assessed using the Patient Health Questionnaire-2 (PHQ-2), which is part of the institution’s universal Distress Screening tool. PHQ-2 score of 2 and above was considered positive screening test for depression. PHQ-2 and KRAS mutation data were extracted from the EMR via the Clinical Data Exchange Network bioinformatics tool and confirmed by retrospective chart review. Chi-square test was used to assess the association between KRAS mutation and depression. Multiple imputation was used to impute the missing values. Results: Of the 484 CRC patients, KRAS status was known in 45 cases: 22 (49%) were KRAS mutated and 23 (51%) were KRAS wild type. PHQ-2 score was 0 in 42 cases (93.3%), 1 in 2 cases (4.4%), and ≥2 in 1 case (2.3%). The rate of positive PHQ-2 for KRAS mutated vs wild type was 4% vs 0% (p = 0.36). The result based on 50 imputed datasets suggests a trend towards an association between KRAS mutation and depression (p = 0.09). Conclusions: This study did not demonstrate an association between KRAS mutation and depression in patients with colorectal cancer, probably due to a high proportion of missing data. Bioinformatics studies that extract and analyze EMR data are a feasible and effective platform to assess the association of genomic data with clinical outcomes. Additional validated algorithms and data are needed to further optimize such studies.
Metastases resection after FOLFIRI-aflibercept (FA) in oxaliplatin-refractory colorectal cancer patients (ORF-CRC).
Authors: Muñoz Martín Andres J. , Garcia Adrian Silvia , Pericay Carles , Ruíz Ana , Ibeas Patricia , Grandez Rosana , Diaz Pena Elena , Lopez Ana Maria , Ignacio Juez MARTEL , Gonzalez Cebrian Irene , Encinas García Sara , Alcaide Julia , Fernandez Montes Ana Fernandez , Soriano Carmen , Macarulla Teresa Mercade , García-Paredes Beatriz , Pulido Gema , Mazo Jose M. , Rodriguez Salas Nuria , Garcia Alfonso Pilar
Published: January 2019

862

Background: Recent data suggest resection of colorectal metastases after second-line chemotherapy offers similar overall survival (OS) benefit compared to what described in first-line. The improvement in response rate with FA in second-line may increase the number of patients eventually undergo metastases resection. Methods: We performed a retrospective analysis of 32 patients from 26 Spanish hospitals who underwent surgical resection after FA in ORF-CRC in real-life setting. Our aim was to analyze the impact of metastases resection in different organs (liver, lung, etc.) in terms of OS and progression-free survival (PFS) and post-surgical mortality and morbidity. Results: Clinical characteristics: Median age: 65 years (43-83). Sex: 78.1% male, 21.9% female. ECOG 0/1 53.1/46.9%. Ras: wild-type/mutated 25/75%. Type of tumor: colon 75.0%, rectal 25.0%. Location: right 28.1%, transverse 9.4%, and left-side 62.5%. Previous treatment: oxaliplatin combinations (100%), bevacizumab 37.5%, cetuximab 21.97%. Ras wild-type patients received previous anti-EGFR therapy. FA in second-line 93.7% and beyond second-line 6.3%. Median FA cycles before surgery: 6.5 (range 3-44). Type of surgery: liver metastases 46.9%, lung metastases 25.0%, cytoreductive surgery for peritoneal carcinomatosis 15.6%, supraadrenalectomy 3.1%, simultaneous liver and peritoneal carcinomatosis 9.4%. Better tumor response with FA (RECIST1.1): partial response 56.3%, complete response 3.1%, stable disease 40.6%. Median follow-up: 20.9 months [m] (range 3.8-57.3 m). Median PFS from surgery: 8.0 m (confidence interval [CI] 95% 2.5-13.5 m). Median OS from surgery: 37.3 m (CI 95% 23.3-51.4 m). No significant difference between right and left-side tumors in OS or PFS were observed. 90-day postoperative mortality/morbidity: 18.8/0% Reoperation rate: 9.4%. Resection rates: R0 75.0%, R1 15.6%, R2 9.4%. Aflibercept after surgery: 22% patients. Conclusions: Metastases resection following FA in ORF-CRC offers encouraging OS with favorable surgical mortality and morbidity. Salvage surgery should be considered in highly selected patients in second-line setting with oligometastatic disease.
Adjuvant therapy for stage II and III colon cancer in elderly patients: NCDB analysis.
Authors: Master Samip R. , Shi Lawrence , Shah Chintan , Shi Runhua
Published: January 2019

863

Background: Data on safety and efficacy of adjuvant chemotherapy for stage II and III colon cancer in elderly patients is area of controversy as these patients are underrepresented in clinical trials. We did a retrospective analysis of Medicare patients aged 70 or older with stage II and stage III colon cancer to investigate the adjuvant chemotherapy effect on colon cancer patients’ survival. Methods: Data was analyzed from 110, 993 men and women (≥ 70 years of age) registered in the National Cancer Database (NCDB) who were diagnosed with AJCC Stage II and Stage III colon cancer between 2004 and 2012 and had follow-ups to end of 2013. The primary predictor variable was adjuvant chemotherapy received, and overall survival was the outcome variable. Only patients with Medicare insurance were investigate for ease of analysis. Additional variables addressed and adjusted included gender, age, race, Charlson Comorbidity Index, the level of education, income, grade of tumor, distance traveled, facility type and diagnosing/treating facility. Results: The mean age was 79.5 years and SD was 5.9 years. In multivariate analysis, after adjusting for secondary predictor variables, receipt of adjuvant chemotherapy was a statistically significant predictor of overall survival of the stage II and stage III colon cancer. Relative to patients who did not receive adjuvant chemotherapy, the patients who got single agent adjuvant chemotherapy had 47.7% and those who were treated with multi agent chemotherapy had 49.8% decreased risk of mortality. There was no significant survival difference between single agent and multi agent adjuvant chemotherapy. Among the factors analyzed, age, gender, race, comorbidity index, diagnosing /treating facility and grade of tumor were found to be significant predictors of survival. Conclusions: Among the patients aged 70 years or older with stage II and stage III colon cancer, adjuvant chemotherapy lead to improved survival outcomes. However, survival difference between single agent vs multi agent adjuvant chemotherapy was not statistically significant.
Local excision for stage I anal canal squamous cell carcinoma (ACSCC): A case series from Mayo Clinic.
Authors: Jin Zhaohui , Chakrabarti Sakti , Hallemeier Christopher Leigh , Mahipal Amit
Published: January 2019

864

Background: Definitive chemoradiotherapy (CRT) is the standard of care for localized or locally advanced ACSCC, while surgery is typically reserved for salvage therapy. Outcome of treatment with local excision alone is unknown and is currently not recommended by NCCN. We retrospectively analyzed outcome of the patients with small (T1 lesion) incidentally found ACSCC who were treated with local excision alone. Methods: On retrospective analysis, a cohort of 12 patients with pathologically confirmed stage I ACSCC treated at Mayo Clinic between 1994 and 2014 was identified who were managed with local excision alone. Baseline as well as followup data were obtained by electronic chart review. Results: Median age of the patients at diagnosis was 68 years (range: 36-81 years) and majority were females (76.9%). Median follow-up duration was 7.5 years. Of the 12 patients, 2 patients did not receive standard CRT due to co-morbid conditions and other 10 patients chose surveillance over CRT. There was only one patient with disease recurrence at 3 years which was salvaged by abdominoperineal resection (APR). This subject remains alive and disease free at the time of data collection (4 years out from APR). There were 4 deaths, all unrelated to ACSCC. Of 12 patients, 10 patients (83%) remained disease free at 5 years and beyond, 1 patient had recurrence and 1 patient was lost to follow up at 5 months from diagnosis. Conclusions: Local excision as a single modality of treatment may be safe and effective for highly selected small stage I ACSCC. Further clinical study is warranted to accurately define the patient population who can be treated with local excision alone, potentially sparing them long term toxicities.
Safety for trifluridine/tipiracil (TAS-102) with bevacizumab combination in patients with refractory metastatic colorectal cancer in real-world clinical practice: The single-institutional experience.
Authors: Yasuda Kayo , Kotani Daisuke , Kuboki Yasutoshi , Fukuoka Shota , Bando Hideaki , Kawazoe Akihito , Nakamura Yoshiaki , Shitara Kohei , Yoshino Takayuki
Published: January 2019

865

Background: Trifluridine/tipiracil (TAS-102) is an oral combination therapy approved for the treatment of patients with metastatic colorectal cancer (mCRC). Phase 1/2 C-TASK FORCE study of TAS-102 plus bevacizumab for patients with refractory mCRC demonstrated a promising efficacy results with mild toxicity profile (Kuboki Y, et al. Lancet Oncology, 2017). The retrospective single-institutional study is aiming to investigate safety of TAS-102 plus bevacizumab for patients with refractory mCRC in real-world clinical practice. Methods: MCRC patients who were refractory or intolerant to a fluoropyrimidine, irinotecan, oxaliplatin, anti-VEGF therapy, and anti-EGFR therapy (if wild-type RAS) and consecutively received TAS-102 plus bevacizumab between January 2016 and June 2017, were analyzed. Adverse events (AEs) were assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0. Results: A total of 33 patients were identified for safety analysis. Patient characteristics were as follows; male/female, 19/14; median age, 59.0 (range 38-81); ECOG Performance Status of 0/1, 21/12; and All wild/ RAS mutant/ BRAF mutant/ unknown, 16/15/1/1. Six patients had received prior regorafenib. The relative dose intensities of TAS-102 and bevacizumab were 87% and 79%, respectively. Grade 3 or higher hematological and non-hematological AEs were follows; leucopenia, 33%; neutropenia, 42%; anemia, 9%; and proteinuria, 12%. There were no febrile neutropenia or treatment-related death. G-CSF was given in 8 patients (24%), while intravenous antibiotics was in one patient. There were four patients with emergency admission, and out of these, the two patients had intestinal perforation, and perianal abscess, which were regarded as treatment-associated; ultimately these AEs were fully recovered. Conclusions: Our findings suggested safety for TAS-102 plus bevacizumab combination in real-world clinical practice is consistent with those in clinical trial setting.
Clinical outcomes of gastric cardia cancer during a recent decade of Korea.
Authors: KO Sung Woo
Published: January 2019

87

Background: To date, the incidence of adenocarcinomas of the gastric cardia has been increasing worldwidely. In 7th edition of the American Joint Commission on Cancer, a tumor within 5 cm of the EGJ is classified and staged according to the esophageal cancer. There are two different etiologies of gastric cardia cancer - Barrett's esophagus and Helicobacter pylori (H. pylori) associated intestinal metaplasia. We aimed to evaluate the clinical characteristics and outcome between gastric cardia and non-cardia cancer. Methods: We performed a retrospective cohort study of 90 patients with gastric cardia cancer from Jan. 2003 to Dec. 2013. We selected 180 patients with gastric non-cardia cancer as age and sex matched control during the same period (by AGE, SEX PROGRAM). Results: The rate of curative resection (R0) was significantly low in gastric cardia cancer (74/81 vs. 146/149) (91.4% vs 98.0%, P=.02) The recurrence rate was lower in patents with non-cardia cancer than those with cardia cancer (21/74 vs. 12/146) (28.4% vs 8.0%, P=.00). Subgroup analysis was done for patients with cardia cancer according to BMI and helicobacter infection and atrophic mucosal change. The median follow up period of obese patients and non-obese patients were 35.0month and 28.0month, which revealed there was no difference (P=.70). We determined patients with mucosal atrophic change and HP infection as a group1, and patients with no mucosal change with non- infective status as a group 2. The median follow up period of group 1 patient and group 2 patients were 26.0month and 36.0month, there was no significant difference. (P=.96). Conclusions: Gastric cardia cancer had a negative prognostic impact, compared with gastric non-cardia cancer. Although a possible heterogeneity in the pathogenesis and biological behavior of gastric cardia cancer would be present, there was no difference in prognosis.
Interim safety and clinical activity in patients (pts) with locally advanced and unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma from a multicohort phase I study of ramucirumab (R) plus durvalumab (D).
Authors: Bang Yung-Jue , Golan Talia , Lin Chia-Chi , Kang Yoon-Koo , Wainberg Zev A. , Wasserstrom Heather , Jin Jin , Mi Gu , McNeely Samuel , Laing Naomi , Goff Laura Williams , Fu Siqing
Published: January 2019

92

Background: Angiogenesis and immunosuppression are hallmarks of tumor growth. This global phase 1 trial evaluates the combination of R (anti-VEGFR2) and D (anti-PD-L1) in pts with G/GEJ by simultaneously targeting these two processes. Methods: This ongoing, multi-cohort, phase 1a/b trial (NCT02572687) enrolled pts with confirmed G/GEJ adenocarcinoma with prior progression on 1 or 2 lines of systemic therapy, measurable disease, ECOG PS 0-1, and baseline tumor tissue. PD-L1 expression was assessed using the SP-263 IHC; MSI status was determined using PCR. Enrolled pts received R (8 mg/kg IV) and D (750 mg IV) every two weeks on a 28-day cycle. Primary objective was to assess safety and tolerability of R+D; preliminary efficacy was also examined. Results: As of 26-May-2017, 29 G/GEJ adenocarcinoma pts were treated. The median age was 55 y; 69% were male; 66% had ECOG PS of 1; 48% had PD-L1 ≥25% expression in tumor or immune cells, 3.5% were MSI-high; and 72% received study treatment as second line for advanced disease. Median duration of treatment was 2.5 mo for R and 3.0 mo for D. Treatment-emergent adverse events (TEAEs) occurred in 29 (100%) pts and 21 (72%) pts experienced grade 3/4 TEAEs, while treatment-related AEs (TRAE) occurred in 24 (83%) pts; none resulted in treatment discontinuation. Ten (35%) pts had grade 3 TRAEs, and no grade 4 or 5. All grade TRAEs occurring in ≥10% of pts were hypertension (34%), fatigue (31%), headache (24%), diarrhea (21%), pyrexia (10%) and decreased appetite (10%). Five pts (17%) reported a serious adverse event related to study treatment. Preliminary efficacy data (RECIST v1.1) showed 5 of 29 pts (17%) achieved a confirmed PR. Only 1 responding pt was MSI high. The overall response rate for pts with PD-L1 ≥25% was 36%. Median PFS was 2.6 mo (95% CI, 1.45 to 6.28). As of data cut-off, 6 pts (21%) remain on treatment. Conclusions: R+D generated no unexpected toxicity, and demonstrated antitumor activity in pts with previously treated advanced G/GEJ adenocarcinoma. Clinical trial information: NCT02572687.
A real-world comparison of multi-modality therapies in locally advanced gastro-esophageal junction (GEJ) cancers.
Authors: Samawi Haider , Tilley Derek , Tang Patricia A. , Spratlin Jennifer L. , Lee-Ying Richard M. , Cheung Winson Y.
Published: January 2019

96

Background: Trials show that addition of systemic therapy and/or radiation to surgery improves survival in GEJ cancers. However, the different regimens have not been directly compared. We examined population-based outcomes of 3 treatments: 1) neoadjuvant carboplatin and paclitaxel plus radiation (CROSS); 2) perioperative epirubicin, cisplatin, and fluoropyrimidine (MAGIC); and 3) cisplatin and fluoropyrimidine with radiation (CisFP). Methods: We reviewed patients diagnosed with GEJ cancer from 2005 to 2015 who received CROSS, MAGIC, or CisFP at 2 tertiary, 4 regional, and 11 community cancer centers in Alberta, Canada. Survival was assessed with Kaplan-Meier curves and compared with the log-rank test. A Cox proportional hazards model was constructed to evaluate the impact of treatment on overall survival (OS). Results: 331 patients were identified. Median age was 63 (IQR 56-69) years and 86% were men. CROSS was used in 217 (65%) cases followed by CisFP in 72 (22%) and MAGIC in 42 (13%). Age, sex, and stage were not associated with treatment selection (all p > 0.05), but a higher proportion of CROSS and CisFP patients had adenocarcinoma (86% and 85%, respectively) compared to MAGIC patients (41%) ( p < 0.01). CROSS and MAGIC correlated with higher surgical resection rates when compared to CisFP (82% vs. 79% vs. 50%, respectively, p < 0.01). Median OS favored CROSS and MAGIC rather than CisFP, but this was not statistically significant (29 vs. 34 vs. 20 months, respectively, p= 0.17). Adjusting for confounders, OS remained similar for MAGIC (HR 0.8, 95%CI 0.5-1.3, p= 0.36) and CisFP (HR 0.7, 95%CI 0.5-1.1, p= 0.10) when compared to CROSS. In addition, age > 65, advanced stage, and lack of surgical resection were associated with increased risk of death (HR 1.5, 95%CI 1.1-2.0, p= 0.02, HR 2.2, 95%CI 1.2-3.9, p< 0.01 and HR 4.1, 95%CI 2.8-5.9, p< 0.01, respectively). Conclusions: OS was similar across all 3 regimens, but outcomes were inferior to those seen in original trials. This observation suggests that GEJ patients in routine practice are different from study participants or that treatment selection may be driven by factors other than trial eligibility criteria.
Phase II study of epacadostat with pembrolizumab in metastatic or unresectable gastroesophageal junction and gastric adenocarcinoma requiring paired biopsies.
Authors: Kardosh Adel , Tseng Diane , Sahaf Bita , Zomet Ativ , Krupa Julia , Fisher George A. , Wang David S , Mackall Crystal , Kunz Pamela L.
Published: January 2019

TPS191

Background: Gastroesophageal junction (GEJ) and gastric adenocarcinomas constitute a major health problem worldwide. Gastric cancer is the fourth most prevalent malignancy and the second leading cause of cancer death worldwide. Furthermore, the incidence of adenocarcinoma of the esophagus, GEJ and gastric cardia has risen faster than any other malignancy in the last 25 years in the United States and other Western countries. Cytotoxic chemotherapy remains the standard treatment, with progression free survival (PFS) for advanced disease of 4 to 6 months and median overall survival (OS) of 7 to 10 months. Pembrolizumab, a PD-1 inhibitor, was recently approved for advanced gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-1, on the basis of a response rate of 13% seen in KEYNOTE 059 (NCT02335411). Combination immunotherapies are hypothesized to build on this response. Methods: This is a single arm, phase II clinical trial of epacadostat, a novel inhibitor of the enzyme indoleamine 2,3 dioxygenase-1 (IDO-1), in combination with pembrolizumab, in metastatic or unresectable gastroesophageal junction or gastric adenocarcinoma. A 6-month PFS of 20% with single agent pembrolizumab is the basis for the null hypothesis. We will enroll 30 patients over 18 months and follow patients for at least 6 months. This design has 80% power to reject a 20% PFS rate, if the true PFS is 39%. Eligible patients must have: adenocarcinoma of the distal esophagus, gastroesophageal junction or stomach; progression on at least one line of prior therapy for metastatic disease, and for HER2+ disease should have received prior trastuzumab; ECOG performance status 0 or 1; willing to undergo two newly-obtained biopsies - before and on-treatment, provided the procedure is not deemed high-risk and is clinically feasible. Notably, PDL-1 expression is not required. The primary endpoint is 6-month PFS, with secondary endpoints of response rate (RR), OS, and the safety and tolerability of the combination. Furthermore, comprehensive immune profiling from patient blood and tumor tissue will be performed. The study opened to accrual in September 2017 (NCT03196232). Clinical trial information: NCT03196232.
JAVELIN Gastric 100: Phase 3 trial of avelumab (anti-PD-L1) maintenance therapy versus continuation of first-line chemotherapy in patients with advanced gastric or gastroesophageal junction cancer (GC/GEJC).
Authors: Moehler Markus H. , Ryu Min-Hee , Lee Keun-Wook , Coskun Hasan Senol , Wong Rachel , Ozguroglu Mustafa , Chung Hyun-Choel , Poltoratsky Artem , Tsuji Akihito , Yen Chia-Jui , Muntean Alina , le Sourd Samuel , Vaccaro Gina M. , Taieb Julien , Boku Narikazu , Sharma Maitreyi , Xiong Huiling , Conti Ilaria , Bang Yung-Jue
Published: January 2019

TPS195

Background: Outcomes with first-line (1L) chemotherapy for GC/GEJC are limited and new strategies to increase efficacy without added toxicity are needed. Avelumab, a human anti-PD-L1 IgG1 monoclonal antibody, is approved for metastatic Merkel cell carcinoma (US and EU) and advanced urothelial carcinoma after progression on platinum therapy (US). In phase 1 studies in advanced GC/GEJC, avelumab showed antitumor activity and a manageable safety profile, including in a subgroup of patients (pts) without progression on 1L chemotherapy who received avelumab as maintenance therapy. JAVELIN Gastric 100 (NCT02625610) is a global, randomized, open-label, phase 3 trial comparing maintenance therapy with avelumab vs continuation of 1L chemotherapy in pts with advanced GC/GEJC who have not progressed after 12 weeks of 1L oxaliplatin/fluoropyrimidine chemotherapy. Methods: Eligible pts have histologically confirmed, unresectable, measurable, locally advanced or metastatic GC/GEJC adenocarcinoma, no prior chemotherapy for advanced disease, no prior therapy targeting T-cell coregulatory proteins, and ECOG PS of 0–1. Pts are not preselected based on PD-L1 expression and pts with HER2+ tumors are excluded. Approximately 466 pts who achieve at least stable disease following 12 weeks of 1L oxaliplatin/fluoropyrimidine chemotherapy will be randomized 1:1 to receive maintenance therapy with either avelumab 10 mg/kg by IV infusion Q2W or continuation of 1L chemotherapy. Maintenance therapy is given until disease progression, unacceptable toxicity, or withdrawal. Primary endpoints are overall survival and progression-free survival. Secondary endpoints include best overall response, quality of life measures, safety (NCI-CTCAE v4.03), and tumor biomarkers. Responses are evaluated per RECIST 1.1 and adjudicated by independent review committee. Enrollment is ongoing at sites in North/South America, Asia-Pacific, and Europe. Clinical trial information: NCT02625610.
A phase 2 trial of CRS-207 and pembrolizumab in adults with recurrence of metastatic gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinomas.
Authors: Kelly Ronan Joseph , Abrams Thomas Adam , Catenacci Daniel V.T. , Wainberg Zev A. , Lin Bruce Shih-Li , Enstrom Amanda , Whiting Chan C. , Wason Prieya , Murphy Aimee , Brockstedt Dirk G. , Moon Anne , Walling Jackie , Lai Rose , Ku Geoffrey Yuyat
Published: January 2019

TPS200

Background: CRS-207 is a live, attenuated, double-deleted Listeria monocytogenes (LADD) strain with a mesothelin expression cassette inserted. CRS-207 has a well-established, manageable toxicity profile and can elicit mesothelin-specific cell-mediated immunity. Clinical activity of CRS-207 has been shown in a separate Phase 1 trial of mesothelioma. In gastroesophageal (GE) cancers, mesothelin expression is estimated between 30% – 50% and has been correlated with poor prognosis. Preclinical models suggest the combination of LADD-based immunotherapeutics and a PD1 inhibitor may induce more sustained anti-tumor responses than either LADD or PD1 inhibitor monotherapy. GE cancers are responsive to PD1 inhibitors in a subset of patients; this trial proposes to evaluate the efficacy of CRS-207 combined with pembrolizumab in patients with relapsed GE cancer, and to correlate clinical activity with mesothelin expression level. Methods: This Phase 2, open-label, single-arm, multicenter clinical study (NCT 03122548) will enroll approximately 79 subjects at 20 sites. Adults with histologically-confirmed, advanced gastric, GEJ, or esophageal adenocarcinomas are eligible. Subjects must have received 1 or 2 prior treatment regimens, which must have included a platinum and a fluoropyrimidine. Subjects must have disease progression with measurable tumors. A pre-treatment biopsy of either the primary tumor or metastatic site is required prior to dosing. Subjects with prior exposure to checkpoint inhibitors or other immunotherapies are excluded. From cycle 1 to 4 during the treatment and evaluation period, pembrolizumab (IV 200 mg) and CRS-207 (IV 1 x 109 CFU) are both administered in 3-week cycles. Afterward, pembrolizumab will be administered once every 3 weeks; CRS-207 will be given once every 6 weeks. CT scans will be performed every 6 weeks to monitor disease status. The primary endpoint is objective response rate defined by RECIST 1.1. Clinical trial information: NCT03122548.
GastroPET: Phase II academic clinical trial evaluating sequential FDG-PET driven preoperative treatment strategy in locally advanced oesophago-gastric cancer in the context of miRNA- and immune-based biomarkers.
Authors: Obermannova Radka , Hejnova Renata , Zdrazilova-Dubska Lenka , Demlova Regina , Slaby Ondrej , Studentova Hana , Petruzelka Lubos , Grell Peter , Vyzula Rostislav
Published: January 2019

TPS202

Background: The standard treatment approach in locally advanced oesophago-gastric cancer (OGC) contains surgery with perioperative chemotherapy (CXT). Nonetheless according to sequential 18FDG-PET-CT only 40–50% of the patients respond to CTX and non-responding patients would perhaps profit from concurrent radiotherapy (CRT). This phase II trial evaluates the sequential FDG-PET driven preoperative treatment strategy of early histopathological response and improved survival. Methods: Approximately 70 pts with resectable locally advanced OGC will be enrolled in this interventional, prospective, non-randomized multicenter trial. Pts will undergo baseline FDG-PET scan and will be given 1 cycle of CXT (FLOT or FOLFOX). FDG-PET scan will be repeated after 14 days and FDG-PET responders with ≥ 35% reduction in SUVmax from baseline to initial treatment will continue with CXT prior to surgery. FDG-PET non-responders will switch to the CRT (weekly carboplatin and paclitaxel with concurrent radiotherapy (45 Gy in 25 fractions) prior to surgery. The main goal of the surgical therapy is to obtain negative surgical margins. Selected miRNAs and immune parameters will be evaluated for their predictive value. Eligibility: biopsy-proven locally advanced resectable oesophago-gastric adenocarcinoma (Siewert I – III) stage Ib – IIIc; endoscopy and endoscopic ultrasound; pts to be fit for the platinum-containing CXT; potentially R0 resectable tumors. The primary objective: the predictive value of FDG-PET dynamics in the preoperative setting for early regression and R0 resection rate. Secondary endpoints: i/ identification of tissue/plasma miRNA and immune-based biomarkers, ii/ disease free survival and overall survival. Status: Opened to accrual in Oct 2017. Clinical trial information: Eudra CT 2017-001264-38. This work was supported by Ministry of Health, Project No: 15 P03-17-29389A and projects LO1413, DRO and LM15089 BBMRI-CZ. Clinical trial information: 2017-001264-38.
Phase II trial of conversion surgery after apatinib in combination with S-1/oxaliplatin (SOX) for patients with unresectable gastric cancer (Ahead-BG301 trial).
Authors: Chen Lin , Zhang Kecheng , Wei Bo , Guo Xin , Xi Hongqing , Li Jiyang , Cui Jianxin , Gao Yunhe , Liang Wenquan , Lu Yixun
Published: January 2019

TPS203

Background: Recent study has showed that selected patients with unresectable gastric cancer could benefit from surgical resection after achieving response following induction chemotherapy. We speculated that apatinib, an inhibitor of VEGFR-2, in combination with chemotherapy could increase response rate and resection rate following systemic therapy. This trial is designed to investigate the efficacy and safety of conversion surgery after apatinib plus S-1/oxaliplatin (SOX) for patients with unresectable gastric cancer (NCT03007446). Methods: This is a prospective, single-arm and open-label Phase II clinical trial. The primary outcome is resection rate after induction chemotherapy for patients with unresectable gastric cancer. The secondary outcomes include objective response rate and overall survival. Main eligibility criteria include patients with at least single non-curative factor confirmed by CT, MRI, PET-CT or staging laparoscopy: unresectable diseases with locally advanced gastric cancer (T4b); hepatic metastasis (H1; less than five lesions, total diameter ≤ 8 cm); peritoneal metastasis (CY1, P1). An estimated enrollment of 20 patients was planned. After receiving two cycles of apatinib (500 mg, oral, qd) plus SOX (S-1: 40mg bid, d1-14 q3W; oxaliplatin: 130 mg/m2, d1 q3W), patients will be subject to multidisciplinary team evaluation for surgery. First patients were enrolled in Dec 2016. Data analysis was planned in Nov 2018. Clinical trial information: NCT03007446.