bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I study of preoperative capecitabine and lenvatinib with external radiation therapy in locally advanced rectal adenocarcinoma.
Authors: Frakes Jessica , Mehta Rutika , Hoffe Sarah E. , Imanirad Iman , Martinez Jimenez Maria E , Sanchez Julian , Malafa Mokenge Peter , Felder Seth , Dessureault Sophie , Kim Richard D. 
Published: January 2019

694 Background: Despite routine use of neoadjuvant chemoradiation, patients with advanced rectal tumors experience significant rates of treatment failure and recurrence. Radiation resistance is a particular problem. Dual targeting of PDGF and VEGFR (Vascular endothelial cell growth factor receptor) in combination with radiation can enhance tumor response. Lenvatinib inhibits the kinase activities of VEGFR1-3, FGFR1-4, PDGFRα, KIT, and RET and in vivo results show that it effectively delays the growth of human colorectal xenografts. Methods: This is a phase I clinical trial of lenvatinib in combination with capecitabine administered with radiation. Patients with stage II or III rectal cancer confirmed by endoscopic ultrasound or MRI were eligible for the study. In this 3+3 phase I study with 3 cohorts, patients were treated with escalating doses of lenvatinib administered in combination with standard doses of capecitabine (850 mg/m2 PO BID D1-5 weekly for 5 ½ to 6 weeks) and external beam radiation therapy (180 cGY on D1-5 weekly for 5 ½ to 6 weeks). Patients underwent surgery 6-10 weeks after neoadjuvant therapy. Results: Nine patients have been enrolled in the 3 cohorts with the median age of 51 years. Lenvatinib dosing started at 14 mg PO daily (cohort 1) and was safely escalated to 20 mg PO daily (cohort 2) followed by 24 mg PO daily (cohort 3). There were no DLTs at the maximum tested dose of lenvantinib (24 mg). 5 patients have undergone low anterior resection and 4 have had abdominoperineal resection. The pathological complete response (pCR) rate was 33.33%, and downstaging was observed in 100% of patients. Median neoadjuvant rectal cancer score (NAR) was 8.7. Three pts had grade 3 events (2 hypertension (HTN), 1 lymphopenia) without any grade 4 events. Most common AEs were HTN and fatigue. No perioperative complications were observed. Tissues for all pts have been collected for planned correlative studies. Conclusions: This study shows that the combination of lenvatinib with capecitabine, and EBRT is well tolerated. NAR score and downstaging rates are encouraging. Currently we are enrolling 10 additional pts at the maximum tested dose of lenvatinib to further evaluate efficacy and safety. Clinical trial information: NCT02935309.
Stage II and III rectal adenocarcinoma outcomes related to lymphovascular invasion.
Authors: O'Brien Shalana BL , Mutabdzic Dorotea , Handorf Elizabeth A. , Devarajan Karthik , Reddy Sanjay S. , Sigurdson Elin R. , Denlinger Crystal S. , Meyer Joshua E. , Farma Jeffrey M. 
Published: January 2019

698 Background: Lymphovascular invasion (LVI) has been shown to be associated with nodal involvement and higher rates of local recurrence in rectal cancer. In some studies, the presence of LVI has also been associated with worse overall survival; however, these have been mostly smaller, single institution studies or incomplete data sets. Our goal was to examine the effect of LVI on prognosis in a large and inclusive database. Methods: Outcomes of patients with clinical stage II and stage III rectal adenocarcinoma in the National Cancer Data Base (NCDB) from 2011 to 2015, in whom LVI data was available, were included. Exclusion criteria incorporated patients who did not receive neoadjuvant radiation and chemotherapy, neoadjuvant or adjuvant. Overall survival was compared in patients with and without LVI, controlling for age, sex, race, comorbidities, socioeconomic factors, and T and N stages using Kaplan-Meier survival curves and Cox proportional hazards regression analysis. Median overall survival and hazard ratios with 95% confidence intervals are reported where available. Results: The dataset included 9206 patients with stage II and 12640 patients with stage III rectal adenocarcinoma for which LVI data were available and who received the study’s previously defined standard of care. The proportion of patients with LVI was 11% in stage II and 16% in stage III rectal cancer. After adjusting for age, sex, race, T or N stage, and other clinical and demographic variables, LVI was associated with worse overall survival in stage II HR 1.87 (1.62-2.16, p < 0.001) and in stage III HR 1.8 (1.61-2.02, p < 0.001) rectal cancer. The median overall survival was not reached in stage II rectal cancer patients without LVI versus 5.73 years with LVI. In stage III rectal cancer, the median overall survival was 6.91 years without LVI versus 6.21 years with LVI. Conclusions: Lymphovascular invasion is an independent risk factor of mortality in stage II and III rectal cancer. Stage II rectal cancer patients without LVI have comparatively good survival of the groups studied, potentially identifying a group of patients that may benefit from de-escalated therapy. Further studies will be guided at identifying if benefits with chemotherapy are associated with LVI status.
Outcomes and utilization of adjuvant chemotherapy (AT) for stage II colon cancer (CC-II) in elderly population.
Authors: Barzi Afsaneh , Jiao Xiayu , Hay Joel W , Sadeghi Sarmad 
Published: January 2019

701 Background: The use of AT in elderly patients (pts) with CC-II is controversial. We used Surveillance Epidemiology End Results (SEER) linkage with Medicare claims to explore the patterns of AT and survival in pts with CC-II diagnosed between 2004-2010. Methods: Colon cancer was identified using ICD-O-3 codes. TNM staging information was used to classify pts as stage II and its subgroups. We restricted our cohort to pts who had surgery within 4 months (mos) of the diagnosis using ICD-9 codes: 45.7x and 45.8x and excluded pts who died within 3 mos after the surgery as well as those who were enrolled on a health maintenance organization. We searched Medpar, outpatient facility, or carrier claims in the 4 mos after surgery to identify pts who received AT using ICD-9 diagnosis and procedure codes, HCPCS, and revenue center codes. Logistic regression was used to assess the relationship between demographics and clinical characteristics of pts in each group and receipt of AT. Kaplan-Meier method was used for survival analysis. We performed a flexible parametric survival analysis to estimate the 3-year overall survival benefit for AT while controlling for demographics and clinical characteristics. Results: A total of 15,310 pts were included in our study. Among those, 14% (n=2,168ss received AT of which 718 (33%) received oxaliplatin containing regimen. Pts and tumor characteristics are reported in the table. After adjusting for pts and tumor characteristics, probability of survival at 3 years was 72.9% for pts who received AT and 74.2% for those who did not, HR=1.06 (95% CI, 0.96-1.17), with P-value: 0.229. The AT use was declining over time. Conclusions: Although AT is used in healthier and higher risk elderly pts with colon cancer, it was not associated with significantly improved overall survival. [Table: see text]
Neoadjuvant treatment in a Mexican cohort of patients with locally advanced rectal cancer: Oncologic outcomes and prognostic factors.
Authors: NIETO GARCIA ZULEYMA , Martos Armendáriz Edgar Omar , Camargo Vanessa Rosas , Flores Balcázar Christian Haydeé , Meneses Medina Mónica Isabel , Salgado Nesme Noel , García Badiola Artemio , Licano Zubiate Mariana , Luna González Laura Esther , Garay Mora Juan Alberto , Gamboa Domínguez Armando , Huitzil Melendez Fidel David 
Published: January 2019

704 Background: Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME) and adjuvant chemotherapy (CT) is the standard of care for locally advanced rectal cancer (LARC). Total neoadjuvant therapy (TNT) consists of induction CT followed by CRT prior to surgery. This is an alternative strategy recommended in guidelines. Objective: To describe neoadjuvant strategies, oncologic outcomes and prognostic factors in a cohort of patients (pts) with LARC treated at a referral center in Mexico City. Methods: We retrospectively reviewed medical records from pts with LARC (T3-T4 or N+) treated with any neoadjuvant strategy at Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán” from January 2010 to December 2015. Clinical and pathological information was registered. Survival was estimated by Kaplan-Meier method. Univariate analysis for prognostic factors was performed and survival was compared by the log rank test. Results: 43 pts were included. Median age was 62 y/o (19-83), 51% were female. Clinical stage (CS) II 9% and CS III 91%. 36 pts were T3-4 and N+(86%). Localization was lower third 30%, middle third 56% and upper third 12%. 63% were moderately differentiated adenocarcinoma. 84% had TNT: induction CT with FOLFOX-4 regimen for 3 months followed by CRT (50.4 Gy in 28 fractions concurrently with fluoropyrimidines) and TME. Surgery: ultra-low anterior resection (AR) 48%, low AR 28% and abdominoperineal resection 24%. One patient did not accept surgery. Of the 32 pts with ultra-low and low AR, 94% had protective ileostomy. The pathologic complete response (pCR) ypT0ypN0 rate was 45% (19/42). Median follow-up was 48 months. There were 8/42 recurrences (19%): local-only 2.3%, systemic only 12% and both 5%. None of the pts with pCR recurred. All pts with residual nodal disease recurred (5/5). The 5-year relapse-free survival rate was 73%. There were 6 deaths, one patient died without disease. The 5-year overall survival rate was 83%. Conclusions: In pts with LARC the TNT is associated with high rates of pCR and favorable oncological outcomes. pCR and residual nodal disease after neoadjuvant therapy were strongly associated with recurrence and survival.
Impact of the prior chemotherapy with two different fluoropyrimidines on the efficacy of CapeIRI or FOLFIRI in metastatic colorectal cancer: An exploratory analysis of the phase III AXEPT trial.
Authors: Kim Tae Won , Muro Kei , Xu Rui-hua , Park Young Suk , Wang Wei , Han Sae-Won , Ota Mitsuyoshi , Ahn Joong Bae , Deng Yanhong , Akiyoshi Kohei , Cho Sang Hee , Ba Yi , Denda Tadamichi , Lee Keun-Wook , Zhang Tao , Matsuda Chu , Yamada Yasuhide , Morita Satoshi , Iwasa Satoru , Sakamoto Junichi 
Published: January 2019

711 Background: Modified CapeIRI (irinotecan 200 mg/m2 on day 1, capecitabine 1600 mg/m2 on days 1–14 every 3 weeks) with or without bevacizumab (± BV) has shown non-inferiority of overall survival compared with FOLFIRI ± BV based on the phase III study, AXEPT, as second-line chemotherapy for patients with mCRC. In this exploratory analysis of the AXEPT trial, we evaluated the impact of the prior chemotherapy with two different fluoropyrimidine backbones (fluorouracil and leucovorin vs oral fluoropyrimidine) on the efficacy of CapeIRI and FOLFIRI. Methods: Patients were randomized to receive standard FOLFIRI ± bevacizumab or modified CapeIRI ± bevacizumab after failure to fluoropyrimidine-based chemotherapy in the AXEPT study. Prior fluoropyrimidine backbones were categorized into oral fluoropyrimidine-based (eg, capecitabine or S-1) regimen (oral 5-FU group) and fluorouracil and leucovorin-based regimen (infusional 5-FU group). Assessed endpoints included overall survival, progression-free survival, response rate, and safety. Results: Prior fluoropyrimidine backbone was available for 642 patients among all 650 randomized patients (oral 5-FU group in 291, and infusional 5-FU group in 351). Median overall survival was 17.0 and 16.7 months for FOLFIRI ± BV and CapeIRI ± BV in the prior oral 5-FU group, and 14.9 and 16.7 months for FOLFIRI ± BV and CapeIRI ± BV in the prior infusional 5-FU group. Median progression-free survival was 7.9 and 8.6 months for FOLFIRI ± BV and CapeIRI ± BV in the prior oral 5-FU group, and 6.8 and 8.3 months for FOLFIRI ± BV and CapeIRI ± BV in the prior infusional 5-FU group. Conclusions: There was no significant difference in the efficacy of CapeIRI or FOLFIRI regardless of prior fluoropyrimidine backbones. Therefore, CapeIRI ± BV could also be effective for patients after failure of oral fluoropyrimidine-based chemotherapy (eg, CapeOX ± BV). Clinical trial information: NCT01996306. [Table: see text]
Preprocedural prediction of non-curative endoscopic submucosal dissection for early gastric cancer.
Authors: Choi Cheol Woong , Kang Dae Hwan , Kim Su Jin 
Published: January 2019

74 Background: Endoscopic submucosal dissection (ESD) has been accepted as the treatment of choice for early gastric cancer (EGC) without lymph node metastasis. However, additional surgical gastrectomy should be considered after non-curative endoscopic resection. We aimed to evaluate the predictive factors associated with non-curative endoscopic resection. Methods: Between November 2008 and June 2015, a retrospective study was conducted in a single, tertiary, referral hospital. A total of 596 EGC lesions resected by ESD were analyzed. Non-curative endoscopic resection was defined as the occurrence of lesions associated with piecemeal resection, positive resection margins, lymphovascular invasion, or lesions that did not meet the expanded indications for ESD. Results: The rate of non-curative endoscopic resection was 16.1%. The mean follow-up period was 35.3 ± 25.0 months. Associated predictive factors for non-curative endoscopic resection were female sex (OR, 2.470; p = 0.004), lesion size ≥ 20 mm (OR 3.714; p < 0.001), longer procedure time (OR 2.449, p = 0.002), ulceration (OR 3.538, p = 0.002), nodularity (OR 2.967, p < 0.001), depression (OR 1.806, p = 0.038), undifferentiated carcinoma (OR 2.825, p = 0.031) and lesion located in the mid or upper third of stomach (OR 7.135 and OR 4.155, p < 0.001, respectively). As the number of risk factors increased, the risk of non-curative ESD also increased. Conclusions: Prior to selection of ESD, the risks associated with non-curative ESD should be considered so that appropriate treatment modalities may be selected.
A phase II, open-label, randomized study to evaluate the efficacy and safety of andecaliximab combined with nivolumab versus nivolumab alone in subjects with unresectable or recurrent gastric or gastroesophageal junction adenocarcinoma.
Authors: Shah Manish A. , Metges Jean-Philippe , Cunningham David , Shiu Kai-Keen , Wyrwicz Lucjan , Thai Dung , Brachmann Carrie , Bhargava Pankaj , Catenacci Daniel V.T. , Wainberg Zev A. 
Published: January 2019

75 Background: Andecaliximab (ADX) is a monoclonal antibody that inhibits matrix metalloproteinase 9 (MMP9). Preclinical studies suggest that MMP9 inhibition relieves immune suppression and promotes T-cell infiltration to potentiate checkpoint blockade. Methods: Phase 2, open-label, randomized study of the efficacy and safety of ADX + nivolumab (NIVO) vs. NIVO alone in patients with pre-treated metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. Patients were randomized to either ADX 800 mg IV + NIVO 3 mg/kg IV, or NIVO 3 mg/kg IV alone, and stratified by tumor PD-L1 status. Treatment was administered every 2 weeks. Re-staging CT scans were performed every 8 weeks to evaluate response. Primary endpoint: objective response rate (ORR). Secondary endpoints: progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Results: Of the 144 patients randomized, 141 were treated, 109 (76%) completed tumor assessment. 81% of patients were white, with 69% male and a mean (SD) age of 59 (12) years. ORR (95% CI) was 11.1% (4.9–20.7%) in patients receiving ADX + NIVO, and 6.9% (2.3–15.5%) in those receiving NIVO alone, p = 0.6. Kaplan-Meier estimated median (95% CI) PFS was 1.8 (1.8–2.0) months in patients receiving ADX + NIVO, and 1.9 (1.7–1.9) months in those receiving NIVO alone, p = 0.2. Kaplan-Meier estimated median (95% CI) OS was 7.2 (5.2–9.1) months in patients receiving ADX + NIVO, and 5.9 (3.5–8.6) months in those receiving NIVO alone, p = 0.4. AEs leading to treatment discontinuation occurred in 1 patient in the ADX + NIVO group, and in 1 patient in NIVO-only group. PD-L1 and mismatch repair deficient subgroup analyses will be presented. Exploratory biomarker analyses will be submitted separately. Conclusions: Addition of ADX to NIVO did not improve ORR, PFS, or OS compared with NIVO alone in patients with pre-treated metastatic gastric or GEJ adenocarcinoma. Combination of ADX with NIVO had a favorable safety and tolerability profile. Clinical trial information: NCT02864381.
A comparison of elderly versus nonelderly patients in the CRITICS gastric cancer trial.
Authors: Slagter Astrid E , Tudela Benjamín , van Amelsfoort Romy , Sikorska Karolina , van Sandick Johanna W. , Van De Velde Cornelis J. H. , van Grieken Nicole C.T. , Lind Pehr A. , Nordsmark Marianne , Putter Hein , Meershoek – Klein Kranenbarg Elma , Jansen Edwin PM , Cats Annemieke , Verheij Marcel 
Published: January 2019

81 Background: Although the proportion of elderly cancer patients (pts) increases, few randomized trials provide separate results on this group. Here, we present a sub-analysis of the CRITICS trial, comparing elderly with non-elderly pts. Methods: Preoperative (preop) chemotherapy (CT) included three cycles of epirubicin, cisplatin/oxaliplatin and capecitabine (ECC/EOC); pts were upfront randomized between postoperative (postop) CT (3x ECC/EOC) and chemoradiotherapy (CRT; 45Gy + cisplatin/capecitabine). Elderly pts were defined as age ≥ 70 years at the time of randomization. We present tolerability and outcomes for elderly versus non-elderly pts. Results: Details on baseline characteristics, preop treatment, surgery, postop treatment and survival are shown in Table 1. Tumor type and localization did not differ between both groups. Conclusions: Age had a significant impact on toxicity and tolerability of preop CT, but did not affect surgical resection rates and complications. Although less elderly pts started postop treatment and elderly pts received lower dose in de CT arm, there were no differences in treatment related toxicities. Survival was not significantly different. Clinical trial information: NCT00407186. [Table: see text]
A retrospective analysis of third-line treatment in advanced gastric cancer.
Authors: Ishizuka Yasunobu , Terazawa Tetsuji , Yukami Hiroki , Yamaguchi Toshifumi , Kuwakado Shin , Kii Takayuki , Goto Masahiro , Higuchi Kazuhide 
Published: January 2019

83 Background: As a result of ATTRACTION2, nivolumab was added to the third line treatment in advanced gastric cancer (AGC), but the response rate was about 10%. As there is no predictive biomarker and no comparison with cytotoxic regimen, it is difficult to choice the regimen. Therefore, we examined the treatment outcome of cytotoxic regimen in third line treatment in the real world retrospectively. Methods: We retrospectively evaluated efficacy and safety of cytotoxic regimen as third-line treatment in patients with AGC between July 2015 and December 2017. Results: Among 138 patients received chemotherapy as first line, 29 patients (21%) received third line therapy. The characteristics were as follows; the median age, 70 years old (range 34-80); male/female, 19 (66%)/10 (34%); performance status (PS) 0/1/2, 7/18/4. The overall response rate was 19% and the disease control rate was 38%. The median overall survival (OS) was 6.6 months and the progression free survival was 3.8 months. The most common grade 3/4 hematological toxicities were neutropenia (27%), followed by anemia (27%) and febrile neutropenia (13.7%). Grade 3/4 nonhematological toxicities included anorexia (27.6%), diarrhea (10%), nausea (10%). Conclusions: Cytotoxic regimen as third line showed acceptable activity, but only 21% of patients could received the third line chemotherapy. The further investigation of predictive biomarker of nivolumab is expected.
Impact of tumor growth rate during preceding treatment on tumor response to nivolumab or irinotecan in advanced gastric cancer.
Authors: Kato Kyoko , Masuishi Toshiki , Fushiki Kunihiro , Nakano Shintaro , Kawakami Takeshi , Kawamoto Yasuyuki , Narita Yukiya , Tsushima Takahiro , Nakatsumi Hiroshi , Kadowaki Shigenori , Todaka Akiko , Yuki Satoshi , Tajika Masahiro , Machida Nozomu , Komatsu Yoshito , Muro Kei , Yasui Hirofumi 
Published: January 2019

84 Background: Although nivolumab (NIVO) and irinotecan (IRI) are recognized as standard third-line and further treatments for patients (pts) with advanced gastric cancer (AGC), the drug that should be administered first remains unclear. Conversely, tumor growth rate (TGR) during preceding treatment was associated with tumor response to regorafenib or trifluridine/tipiracil in colorectal cancer. Methods: We retrospectively evaluated 212 pts with AGC treated with NIVO or IRI for the first time between January 2015 and June 2018 at three institutions. The main inclusion criteria were ECOG PS of 0–2, prior use of fluoropyrimidines and taxanes, and no prior use of NIVO or IRI. Pts were classified into slow- (SG) and rapid- (RG) growing groups according to TGR and presence or absence of new lesions (NL) during preceding treatment. TGR = (D1 − D0)/100D0 (CT1 − CT0), where CT1 is the date of CT at PD during preceding treatment, CT0 is the date of CT before CT1, and Dn is the sum of target lesion diameters at CTn. SG and RG were defined as NL− with low TGR and NL− with high TGR or NL+, respectively. TGR cut-off value was defined as a median TGR of 0.30%/day. Results: A total of 117 pts (RG/SG, 72/45; NIVO/IRI, 32/85) were eligible. Almost all baseline characteristics were similar between the NIVO and IRI groups among the RG or SG, whereas the proportion of pts with peritoneum metastases was higher in the NIVO group than in the IRI group among the RG. The response rate (RR) was significantly higher with NIVO than with IRI [31% vs. 3%, odds ratio (OR): 13.8, p = 0.01; adjusted OR (aOR): 52, p = 0.002] among the SG, whereas it was comparable between both drugs (5% vs. 8%, OR: 0.68, p = 0.73; aOR: 0.94, p = 0.96) among the RG. PFS was longer with NIVO than with IRI [median PFS (mPFS) 4.2 vs. 1.9 months (m), hazard ratio (HR): 0.50, p = 0.10] among the SG, whereas it was shorter with NIVO than with IRI (mPFS 1.6 vs. 2.1 m, HR: 1.37, p = 0.28) in the RG. Conclusions: RR was higher with NIVO than with IRI among slow growing tumors, whereas it was comparable between both drugs among rapid growing tumors. TGR during preceding treatment might be helpful for drug selection in pts with AGC who are considered for treatment with NIVO or IRI.