bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical outcome for continuous versus intermittent chemotherapy for unresectable metastatic colorectal cancer: Comparative analysis after first-line therapy.
Authors: Abdallah Nadine , Mohamed AMR , Ismail Hibah , Chen Wei , Akhras Alaa , Jang Hyejeong , Smith Daryn W. , Tesfaye Anteneh A. , Philip Philip Agop , Shields Anthony Frank 
Published: January 2019

825 Background: Colorectal cancer (CRC) is the third most common and second most lethal cancer in the U.S, with almost 50% of patients developing metastatic disease. Although survival of metastatic CRC (mCRC) has improved significantly, current treatment strategies are associated with many adverse effects. With no prospect of cure, goals of treatment should consider both quantity and quality of life. Interruption of chemotherapy after induction can represent a means to achieve this balance. Methods: The primary objective of this meta-analysis is to assess the effect of continuation vs interruption of systemic therapy in terms of survival in patients with unresectable mCRC after first line treatment. Among 15 prospective studies published from 2009-2017, 9 qualified for inclusion. Random-effect model was used for pooled effects within two main categories: continuous chemotherapy vs chemotherapy-free interval after first line induction. Studies with maintenance fluoropyrimidine and/or bevacizumab were excluded. Primary endpoint was median progression free survival (PFS) and secondary endpoint was median overall survival (OS). z statistics were used for comparing subgroups. All statistical tests were two-sided. P values < 0.05 were considered significant. Results: 1366 patients (55% males) were included in the final analysis. Induction treatment was 5-FU or capecitabine-based chemotherapy with either oxaliplatin or irinotecan with or without bevacizumab. After stratifying for induction status, there was no statistically significant difference in median PFS between continuous vs chemotherapy free interval [Median PFS 4.74-month (95% CI 3.87-5.61) vs 3.52 month (95% CI 2.97-4.07), z-test adjusted p value 0.1383]. No significant difference in median OS between both groups [Median OS 16.95-month (95% CI 15.40-18.50) vs 18.35 month (95% CI 15.17-21.54)]. Conclusions: In mCRC patients, the superiority of continuous chemotherapy was not demonstrated. Further studies should shed light on patient and tumor characteristics most likely to benefit from continuous chemotherapy to limit delivery of cytotoxic therapy to this subset of patients.
Clinical outcome and prognosis of metastatic colorectal cancer (mCRC) patients (pts) on phase 1 trials: A single institution experience from 1999 to 2016.
Authors: Kam Audrey E. , Pendurti Gopichand , Shah Umang H. , Ghalib Mohammad Haroon , Chaudhary Imran , Viswanathan Sengottuvel , Mantzaris Ioannis , Goel Sanjay 
Published: January 2019

828 Background: Pts with mCRC who progress on all standard therapies have a poor prognosis and limited therapy options. Phase 1 trials represent a valuable treatment option. Herein we report the characteristics and outcomes of mCRC patients treated at our institution. Methods: We reviewed records of pts with mCRC enrolled on phase I trials at our institution from January 1999 to December 2016. Treatment-related response, toxicity, and deaths were recorded. Prognostic factors for overall survival (OS) were calculated using univariate (UVA) and multivariable Cox PH analysis (MVA). Results: We observed 187 enrollments with 152 unique patients accrued on 37 phase I trials. Median age was 59 years (range 29-83) and median number of prior therapies was 3 (range 0-8). 144 patients were evaluable for response. The clinical benefit rate (SD+response, CBR) was 33.2% and the ORR was 4.3%. Grade 3/4 non-hematological and hematological AE were seen in 25.5% and 17.3% of patients, respectively. Treatment-related mortality was 0.5%. Median PFS was 1.7 mos and OS was 8.2 mos. In UVA, the following variables predicted a shorter OS: age (p = 0.049); PS > 1 (p < 0.01); sites of metastases > 2 (p = 0.04); LDH > ULN (p < 0.001); albumin < 3.5 (p < 0.001); direct bilirubin > ULN (p = 0.02); WBC > 5.2 (p = 0.001); anemia (p = 0.046). In MVA, age > 60 (HR 1.63, p < 0.004), albumin < 3.5 (HR 3.69, p < 0.001), direct bilirubin > ULN (HR1.69, p < 0.01), and WBC > 5.2 (HR 1.97, p < 0.001) were negative prognostic factors for OS, adjusted for race and sex. A risk score based on MVA revealed that patients with a score of 0-1 had an improved OS (12.5mos) compared to a score of 2 (9.1mos, p-value < 0.005) and 3 (3.2 mos, p-value < 0.001). Conclusions: Patients with mCRC enrolled on phase 1 trials had a CBR of 33.2% and median OS of 8.2 mos, which exceeds third line therapies including regorafenib and trifluridine/tipiracil. Negative prognostic factors for OS were: age > 60, albumin < 3.5, direct bilirubin > ULN, and WBC > 5.2. A risk score based on these parameters showed that patients with a higher score had a significantly shorter OS, which may be useful in selecting patients for phase 1 trials.
Clinical characteristics and outcomes of metastatic or recurrent gastric cancer with high progranulin expression in patients who had received palliative chemotherapy.
Authors: Koo Dong-Hoe , Do Ingu , Yoo Tae-Kyung , Oh Sukjoong , Lee Yun-Gyoo , Kim Kyungeun , Sohn Jin Hee , Park Jung Ho , Sohn Chong Il , Son Byung Ho , Serrero Ginette , Yoo Chang Hak 
Published: January 2019

83 Background: Progranulin (PGRN), characterized as an autocrine growth and survival factor, is known to stimulate the tumorigenesis and proliferation of several cancer cell types. However, little is known about the prognostic role of PGRN in metastatic or recurrent gastric cancers (MRGCs). Methods: A retrospective analysis was performed on patients with MRGCs who had received palliative chemotherapy between January 2010 and March 2014. PGRN expression in tumor cells by immunohistochemical staining was calculated as the product of proportion (0 = none; 1 ≤ 25%; 26% ≤ 2 ≤ 50%; 3 > 50%) and intensity score (0, no staining; 1, weak; 2, moderate; 3, strong), and categorized as high expression (Score ≥ 4) or low expression ( < 4). Results: A total of 101 patients were analyzed with the median age of 57 years (range, 24–79) at first-line chemotherapy, and 66 patients (65%) were male. Twenty-three patients (23%) had high PGRN expression tumors, and they were almost younger patients (≤ 65 years, 96%). In terms of metastatic sites, the patients with high PGRN tumors had more liver metastasis (30% vs. 17%), and the patients with low PGRN had more bone metastasis (10% vs. 4%). There were no significant differences in the proportion of patients with a response to chemotherapy (32% vs 38%) between patients with high or low PGRN tumors. The median follow-up duration of surviving patients was 54.8 months (range 34.5-81.4 months). Overall, 90 patients (89%) died, and a median overall survival (OS) and progression free survival (PFS) were 13.1 months (95% CI, 9.5–16.8 months) and 5.6 months (95% CI, 4.7-6.5), respectively. The PFS and OS were not statistically different between patients with high PGRN tumors and those that were low PGRN (median PFS 5.2 vs 5.9 and OS 14.9 vs 13.0 months, P = 0.471 and 0.927, respectively). In addition, multivariate analysis showed that PGRN expression was not a prognostic factor in both PFS and OS after adjusting for possible confounding factors including sex, age, performance, histopathology and number of metastasis. Conclusions: There was no relationship between PGRN expression and response to chemotherapy or prognosis in patients with MRGCs.
Barriers for access to isolated liver metastasis treatment in colon cancer in the United States.
Authors: De Souza Andre Luiz , Rathore Ritesh , Mukkamalla Shiva Kumar Reddy 
Published: January 2019

833 Background: Multidisciplinary treatment of stage IV colon cancer with isolated hepatic metastases implies patient’s access to quality healthcare. Here, we evaluate barriers for access to hepatic metastasectomy in the United States. Methods: The National Cancer Database was queried for stage IV colon cancer patients with isolated liver metastasis diagnosed from 2010-2014. Patient demographics, T and N staging, laterality and surgery were among the variables of interest. Pearson Chi square test was used for statistical analysis Results: A total of 3145 patients were identified for analysis. Moderately differentiated, T3 and N1 tumors were the most frequent tumors to be treated with perioperative and neoadjuvant chemotherapy. Neoadjuvant and perioperative chemotherapy correlated with age (p<0.0001) and year of diagnosis (p=0.0289). Left sided tumors were more likely to receive perioperative and neoadjuvant chemotherapy compared to right sided or transverse tumors (p<0.0001). Conclusions: With various degrees of utilization of perioperative and neoadjuvant chemotherapy based on demographic and clinical variables, there exists a great need to close the gap in access to chemotherapy and surgery for colorectal cancer isolated liver metastases. [Table: see text]
Qualitative analysis of Iowa rectal cancer patients’ decisions on where to receive surgery.
Authors: Charlton Mary E. , Shahnazi Ariana , Gribovskaja-Rupp Irena , Lin Chi , Hunter Lisa , Chrischilles Elizabeth A. , Lynch Charles F , Ward Marcia M 
Published: January 2019

835 Background: Current literature suggests surgeons and hospitals that perform large volumes of rectal cancer care achieve superior outcomes, but only about half of rectal cancer resections are performed by high-volume surgeons in comprehensive hospitals. Little is known about considerations of patients with rectal cancer when deciding where to receive surgery. Methods: A purposive sample of stage II/III rectal adenocarcinoma survivors diagnosed 2013-2015 were identified through the Iowa Cancer Registry and interviewed by telephone about factors influencing decisions on where to receive rectal cancer surgery. Interviews were recorded and transcribed, and a thematic analysis was conducted. Results: Thematic saturation was reached after interviewing 15 survivors. Mean age was 63; 60% were male, 53% resided in non-metropolitan areas and 60% received surgery at low-volume centers. Recommendation from a trusted source, usually a physician, appeared to be a main driver of where patients received surgery. Patients who chose high-volume centers were directed by a trusted source to seek care there, whereas patients who chose low-volume centers described valuing hospitals that were closer to home, knowing individuals at the hospital and receiving prior care there, and being familiar with others who received care from a specific surgeon. Most considered surgeon volume and experience to be important determinants of outcomes, but few actually assessed it. Most characterized surgeon experience based on subjective assessments including interpersonal skills, ability to explain procedures and perceived surgeon confidence. Several reported not trusting online sources for treatment information. Conclusions: Most rectal cancer patients in our sample relied on physician referrals to decide where to receive surgery. Further research is needed to determine rectal cancer patients’ preferences for obtaining information about surgeon/hospital volume and experience since our findings suggest they are neither discussing these factors with their surgeon nor researching them on their own. Once preferences are determined, targeted interventions facilitating more informed decision-making by patients can be developed.
Mutational landscape of metastatic colorectal cancer: Aggregate insights from a molecular tumor board.
Authors: Lewis Mark Andrew , Haslem Derrick S. , Thota Ramya , Rhodes Terence Duane , Barker Tyler , Moulton Bryce , Abraham Tyler , Fulde Gail , Romero Robin , Christensen Bryce , Nadauld Lincoln 
Published: January 2019

837 Background: The mutational landscape of metastatic colorectal cancer (CRC) is being elucidated by next-generation sequencing of both primary tumors and metastatic foci. In this study, we examined the results of all stage IV CRC cases submitted to our molecular tumor board (MTB). Methods: We performed a retrospective analysis of all patients who had next-generation sequencing performed between January 2015 and August 2017 on either their primary tumor and/or metastasis. Cases were presented at a MTB convened twice monthly. For the purposes of this study only pathogenic mutations were notated, not variants of unknown significance (VUS). Results: Eighty-seven unique patients had 97 specimens sequenced (28 primary tumors and 69 metastases). The primaries averaged 3 mutations per specimen (range: 1-6) whereas the metastases averaged 4 (range: 1-14, p=.25). The most common anatomic sites of submitted metastatic tissue were the liver (n=35, average mutations=4), followed by the lungs (n=10, average mutations=3) and the omentum/peritoneum (n=8, average mutations=3). Two patients had both a primary tumor and a metastasis sequenced, with a 33% rate of concordance in inter-specimen mutations. Five patients had multiple metastases sequenced, with a 53% rate of concordance in inter-specimen mutations; in every case of longitudinal sequencing, mutational burden increased in metastases over time. The most common mutation was apc (21% of all mutations), followed by p53 (16%) and then kras (13%). Candidacy for EGFR-directed therapy was found in 8 cases, and mismatch repair defects were detected in 5 cases. Conclusions: In stage IV CRC cases sent to our MTB, tissue from metastases was more commonly submitted for analysis than from the primary tumors. There is not necessarily concordance between mutations in primary tumors and metastases, nor among multiple metastases in the same patient. Sequencing at multiple time points in the disease course may allow observation of clonal evolution and dynamic adaptation of therapeutic targets.
Pemetrexed monotherapy as salvage treatment in metastatic colorectal cancer patients who failed standard chemotherapy: A phase II single-arm prospective trial.
Authors: Lim Sung Won , Cho Jangho , Lee Jeeyun , Park Se Hoon , Park Joon Oh , Park Young Suk , Lim Ho Yeong , Kang Won Ki , Kim Seung Tae 
Published: January 2019

840 Background: We designed a single-arm, open label phase II study to determine the efficacy and toxicity of pemetrexed monotherapy with vitamin supplement in refractory colorectal (CRC) patients who failed standard treatments, including 5-FU, oxaliplatin, and irinotecan with or without biologic agents. Methods: Patients were treated with pemetrexed 500 mg/m2 on day 1, every 3 weeks, with folic acid and vitamin B12 supplementation. Patients began vitamin supplementation with B12 intramuscular injection (1000 mcg) every 9 weeks starting 1 week before the first pemetrexed dose, and patients received daily oral folic acid (1 mg) starting at least 5 days before the first pemetrexed dose. Treatment was continued until disease progression or intolerable toxicity was observed. Results: Between June 2016 and October 2016, 24 patients were enrolled in this study. One patient withdrew content, leaving a total of 23 patients to be evaluated. The median age of the patients was 54.0 years (range, 23.0 to 67.0), and the median ECOG performance status was 1 (1-2). The median number of previous systemic chemotherapies was 3 (range, 2 to 5). No complete response and no partial response were observed among the patients. Stable disease was observed in 10 patients (43.4%), and 7 patients had a response duration of 2 months or more. The median PFS was 1.6 months (95% CI, 1.1 to 2.0) and the median OS was 9.8 months (95% CI, 5.9 to 13.6). Only one patient experienced treatment-related toxicity of grade 3 or more. Neither hematologic toxicities nor dose reduction due to treatment-related toxicities were observed. There was no treatment-related death. Conclusions: Pemetrexed monotherapy showed moderate disease control and an acceptable toxicity profile as salvage therapy for refractory CRC. Clinical trial information: NCT02588781.
Laparoscopic resection followed by decompression with a drainage tube for obstructive colorectal cancer.
Authors: Kagawa Yoshinori , Murata Kohei , Naito Atsushi , Kawai Kenji , Takeda Yutaka , Takeno Atsushi , Masuzawa Toru , Ohmura Yoshiaki , Katsura Yoshiteru , Murakami Kohei , Sakamoto Takuya , Mori Ryota , Nose Yohei , Toya Keisuke , Yukawa Yoshiro , Takase Kouki , Kato Takeshi 
Published: January 2019

844 Background: Obstructive colorectal cancer is an oncological emergency that requires emergency treatment. In Japan, laparoscopic resection after decompression with metallic-stent placement is becoming mainstream as a bridge to surgery (BTS). However, there are reports of worse prognoses due to stent placement, and the European Gastroenterology Society of Endoscopy guidelines do not recommend BTS. In our department, since 2011 the first choice of the treatment has been laparoscopic resection after decompression with a trans-anal or trans-nasal drainage tube. STo investigate the safety and short- and long-term results of laparoscopic resection after decompression with a drainage tube. Methods: Eighty-one cases of obstructive colorectal cancer that underwent surgery at our hospital from 2011 to 2016 were investigated with regards to the short- and long-term outcomes of treatment strategies for obstructive colorectal cancer. Results: The median age was 72 years old (39-94). The ratio of male to female was 46:29. The success rate of decompression was 86.7% (66 cases). Stages II, III and IV were involved in 25, 28 and 28 cases, respectively. The causes of the emergency operations were an inability to insert both the ileus tube and the stent (9.3%, 7 cases), and perforation (2.7%, 2 cases) when the trans-anal ileus tube was inserted. In the cases in which decompression was possible, the laparoscopic operation rate was 89.4% (56 cases) and the primary resection rate was 90.9% (59 cases). The median surgical time was 194 minutes (27-325), the median blood loss was 10 g (0-660 g),The median postoperative hospital stay was 14 days (5-147 days). The rate of anastomotic leak was 4.5%. There were no deaths within 30 and 90 days after surgery. The relapse free survival rate in Stage II and III were 72% and 67.9%, respectively. The median months of overall survival in Stage II, III and IV were 60.4, 56.3 and 18.7, respectively. Conclusions: A treatment strategy with laparoscopic resection followed by decompression with a drainage tube was performed feasibly and safely. At this time, the effects of a stent on oncological prognosis is unclear, and this strategy could be an effective treatment for obstructive colorectal cancer.
Social and contextual factors and their relationship with the use of palliative chemotherapy in patients with metastatic colorectal cancer (mCRC): A retrospective cohort study.
Authors: Ahmed Shahid , Iqbal Nayyer , Haider Kamal , Chalchal Haji I. , Le Duc , Alvi Riaz , Zaidi Adnan , Pahwa Punam 
Published: January 2019

849 Background: Although there is evidence that social and contextual factors such as living alone are associated with outcomes in cancer patients, little is known about their influence on the use of palliative chemotherapy in mCRC. We previously reported various patient-and tumor-related factors that correlate with the use of palliative chemotherapy in mCRC (Oncology. 2015;88:289). In this study we examine social and contextual factors including marital status, having children and distance to cancer center for their association with the use of chemotherapy in patients with mCRC. Methods: A cohort of 569 patients with mCRC diagnosed from 2006-2010 in Saskatchewan was evaluated. Logistic regression analyses were performed to assess relationship between the use of chemotherapy and various variables. Results: Median age was 69 yrs (IQR 59-77) and M:F was 59:41. 326 (57%) patients received chemotherapy. Significant differences were noted between the chemotherapy vs. no chemotherapy groups with respect to median age (62 vs. 76 year, p < 0.001), WHO performance status (PS) > 1 (18 vs. 58%, p < 0.001), comorbid illness (24 vs 63%, p < 0.001), low albumin (61 vs. 89%, p < 0.001), anemia (61 vs. 87%, p < 0.001), elevated alkaline phosphatase (53 vs. 84% < 0.001), elevated creatinine (6 vs. 11%, p = 0.025), hyponatremia (20 vs. 14%, p = 0.03), primary tumor resection (61 vs 47%, p = 0.001), metastasectomy (21 vs. 9%, p < 0.001), mean distance to cancer center (98.7±113.6 vs. 127.8±124.6 km, p < 0.001), married/partnered (67 vs 33%, p < 0.001), and having children (64 vs. 36%, p < 0.001), respectively. On multivariate logistic regression analysis after adjustment of other variables, WHO PS > 1 (HR 5.1; 95%CI: 3.1-81.), not having children (3.3, 1.78-6.2, < 0.001), elevated alkaline phosphatase (HR 2.9; 95%CI: 1.8-4.8), and low albumin (HR 2.2; 95%CI: 1.2-3.8), were correlated with low rates of chemotherapy. Marital status or travel distance did not correlate with use of chemotherapy. Conclusions: Our results show that use of chemotherapy in patients with mCRC significantly varies in those with and without children. Future study are required to explore this difference.
Chemoradiation for the treatment of locoregional squamous cell carcinoma of the anal canal: A single center retrospective analysis in Japan.
Authors: Takahashi Ryo , Wakatsuki Takeru , Shinozaki Eiji , Taguchi Senzo , Fujimoto Yoshiya , Osumi Hiroki , Ota Yumiko , MATSUSHIMA TOMOHIRO , Ogura Mariko , Ichimura Takashi , Takahari Daisuke , Suenaga Mitsukuni , Chin Keisho , Oguchi Masahiko , Ueno Masashi , Yamaguchi Kensei 
Published: January 2019

851 Background: Squamous cell carcinoma of the anal canal (SCCA) is a rare malignancy. In western countries, chemoradiotherapy (CRT) has become the standard treatment for locoregional SCCA according to National Comprehensive Cancer Network guidelines. But only some small amount case reports have been found about CRT for SCCA in Japan. We retrospectively evaluated the results of CRT for SCCA at a single center in Japan. Methods: We had treated 33 patients with the concurrent CRT at the Cancer Institute Hospital between 2007 and 2017. RT consisted of 45.0 to 59.4 Gy given in 5 to 7 weeks, with a daily dose of 1.8 Gy. Chemotherapy was given during RT: 1000mg/m2 daily fluorouracil (FU) as a continuous infusion on day 1 to 4 and 29 to 32, and a single dose of mitomycin C (MMC) 10mg/m2 administered on day 1 and 29. Data on relapse and deaths were obtained until August 2017. Results: Of 33 patients who were treated with CRT, the median age was 59 (range 35-82) years. Male to female sex ratio was 1:4.5. Patients who had Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 were 88% and patients who had ECOG PS 1 were 12%. The clinical stages before CRT were cStage I in 9 (27%), II in 4 (12%), IIIA in 6 (18%) and IIIB in 14 (42%). Although clinical complete response (CR) was observed in 29 patients of 33 (88%), 5 patients of 29 recurred. No patients recurred in cStage I and II. SCCA remained or recurred in 2 patients of 6 in cStage IIIA and 7 patients of 14 in cStage IIIB. 3-year disease free survival (DFS) was 71.3% (95%CI: 52.0-84.0%), and 3-year overall survival was 81.8% (95%CI: 55.1-92.8%). Conclusions: CRT for SCCA resulted in clinically meaningful impact on DFS and OS in our hospital. Therefore, CRT may be the standard of treatment also in Japan.