bluuebunny/crossref_metadata_2025 huggingface dataset:
A prospective study of robotic rectal surgery for carcinoma rectum assessing the functional and oncological outcomes: Hype or hope?
Authors: Somashekhar S.P. , C Rohit Kumar , Rajgopal Ashwin K , Zaveri Shabber , Rauthan Amit , Yethadka Ramya
Published: January 2019

661

Background: Robotic surgical systems have dramatically changed minimally invasive surgery as they could potentially address limitations of laparoscopic rectal surgery. This prospective observational study is conducted to evaluate the safety, technique, and outcomes (operative, postoperative,functional and oncological long term) of robotic-assisted rectal surgery for carcinoma rectum in the Indian set up. Methods: This was a prospective observational study conducted between 2010 and 2018, including 135 patients, diagnosed of rectal carcinoma. Patients underwent robotic rectal cancer surgery in form of either low anterior resection (LAR) or abdominoperineal resection (APR). Intraoperative, postoperative data were analysed. Results: Out of 135 patients, 67.5% were male, aged between 34-80 years, 85% had ECOG 0. All patients had adenocarcinoma rectum, with 15% mid rectum and 55% in lower rectum. 85% had stage III disease. 77.5% had received neoadjuvant chemoradiation. 82.5% had LAR and 17.5% APR. Average operative time including docking time and surgery time was 226.32 min (170-300 min), mean blood loss was 146.76 ml (120-200 ml), there were 3 conversion to open surgery. Bowel sounds appeared on average on 3rd day. All margins were negative in all patients, mesorectal grade was complete in 95% and near complete in 5%. Mean number of lymph nodes harvested is 9.5 (2-32). Complete pathological response rate was 39%. 2 patients had anastomotic dehiscence after 1 month. Minor complications were noticed in 10% patients. All had acceptable quality of life and well retained bladder function, with 18% sexual dysfunction. Five year DFS was 85% and OS was 94%. Local recurrence was 2.1%. Conclusions: This is one of the largest single center Indian data available. In conclusion, robotic rectal surgery has several benefits in the treatment and should be part of the armamentarium of the experienced surgeon dealing with rectal cancer. We conclude that the robotic-assisted rectal cancer surgery is safe and an oncologically feasible technique with well retained functional outcomes and has lived up to its hope.
Simultaneous resection of colorectal cancer with synchronous liver metastases: A survey-based analysis.
Authors: Griffiths Christopher , Bogach Jessica , Simunovic Marko , Ruo Leyo , Hallet Julie I. , Serrano Aybar Pablo Emilio
Published: January 2019

662

Background: Decision to proceed with simultaneous or staged resection in synchronous colorectal cancer liver metastases (CRLM) varies and is usually left to the individual surgeon. We examined practice intentions and barriers to performing simultaneous resection. Methods: We developed and pilot-tested a tailored questionnaire. Members of the Society of Surgical Oncology and the College of Physicians and Surgeons of Ontario operating colorectal cancer were surveyed electronically. Four clinical scenarios of synchronous CRLM determined practice intentions for varying degrees of complexity. Perceived barriers were assessed on a 7-point Likert scale. We compared general and hepatobiliary surgeons’ responses with Mann-Whitney U test for continuous variables and Chi-square test for categorical variables. Results: There were 184/1,335 surgeons (14% response rate), including 50 general and 134 hepatobiliary surgeons. Both were supportive of simultaneous resection, though hepatobiliary surgeons were more so; for minor liver and low complexity colorectal resections (Likert ≥5-7: 83% vs. 98% p<0.001), or for complex colorectal resections (57% vs. 73% p=0.042). Both groups were less supportive of simultaneous resection for complex liver with low complexity (Likert ≥5-7: 26% vs. 24% respectively, p=0.858) or high complexity colorectal resections (11% vs. 7.0% respectively, p=0.436). All perceived that simultaneous resection increases post-operative morbidity (63%), but not mortality (69%). Among hepatobiliary surgeons, the most common barriers for simultaneous resections were comorbidities and extrahepatic disease, whereas general surgeons were more concerned about transfer to another facility. Conclusions: While general and hepatobiliary surgeons are supportive of simultaneous resection, especially for less complex liver resections; support is significantly lower among general surgeons. In addition to complexity of procedures and perceived morbidity, the need for transfer of care appears as a barrier to simultaneous resections. The practice intentions and barriers described are important to identify knowledge gaps, guide future trials, and establish disease care pathways.
Simultaneous versus staged resection for synchronous colorectal cancer liver metastases: A population-based cohort study.
Authors: Bogach Jessica , Wang Julian , Parpia Sameer , Simunovic Marko , Hallet Julie I. , Serrano Aybar Pablo Emilio
Published: January 2019

665

Background: While considered safe, simultaneous resection of colorectal cancer primary and liver metastases is not performed routinely. We aimed to identify practice patterns, short and long-term outcomes of simultaneous vs. staged resections for synchronous colorectal cancer liver metastases. Methods: We conducted a population-based cohort study of patients undergoing resection for synchronous colorectal cancer liver metastases from 2006-2015 by linking administrative healthcare datasets in Ontario, Canada. Resection of the primary colorectal cancer and liver metastases within six months was considered synchronous disease. Simultaneous (same hospital admission) and staged resections were compared. Outcomes were 90-day post-operative mortality, total length of hospital stay, overall survival and healthcare costs. Survival for the staged group was measured from the last surgical resection to death and estimated using Kaplan Meier. Cost analysis was undertaken from the perspective of a third-party payer and compared using t test. Results: Of 2,738 patients undergoing colorectal and liver resection for colorectal cancer, 1,168 were synchronous, of which, 442 underwent simultaneous resection. The rate of simultaneous resections increased on average by 3% per year (p = 0.02). Median total length of stay was shorter (8 vs. 11 days); 90-day post-operative mortality was higher for simultaneous resections (3.4% vs 1.2%). Median overall survival was worse with simultaneous resection (40 months, 95%CI 35-46 vs. 78 months, 95%CI 59-86), with a 5-year overall survival of 37% (simultaneous) and 55% (staged). Mean overall costs were lower for simultaneous resections ($12,722 CAD vs. $16,455 CAD. Conclusions: Simultaneous resection compared to staged resection for patients with synchronous colorectal cancer liver metastases is associated with higher 90-day postoperative mortality and worse survival. It was associated with shorter length of hospital stay and lower costs for the health cares system. Considering selection bias, randomized studies would be necessary to determine the role of simultaneous resection for synchronous disease colorectal cancer liver metastases.
Real-world experience of trifluridine/tipiracil in patients with metastatic colorectal cancer: A multicenter United Kingdom study.
Authors: Stavraka Chara , Pouptsis Athanasios , Kabuubi Paul , Angelis Vasileios , Synowiec Alicja , Baxter Mark , Barrie Ainsley , Andres Costa Amparo , Nizam Alia , De Naurois Julien , Mikropoulos Christos , Hill Mark , Graham Janet Shirley , Harris Victoria , Bridgewater John A. , Ross Paul J.
Published: January 2019

668

Background: TAS-102 is an orally administered combination of the thymidine-based nucleic acid analogue, trifluridine and the thymidine phosphorylase inhibitor, tipiracil hydrochloride. Following the phase III RECOURSE study, it received approval as third line treatment for metastatic colorectal cancer showing significant improvement in overall and progression free survival and an acceptable toxicity profile. Methods: We performed a multicenter retrospective observational study of patients with metastatic colorectal cancer receiving TAS-102 as third line treatment between 2016 and 2018 in Cancer centers across the UK. Results: A total of 143 patients were included (94 men, 49 women). Median age was 68 years (35-82). All patients had received at least 2 lines of fluoropyrimidine-based chemotherapy doublet with oxaliplatin or irinotecan. About 90% of patients had ECOG ≥ 1. Median duration of treatment was 2.9 months (0.5-22.9), with a response rate of 1.6% and stable disease achieved in 24%. Median OS was 7 months (95% CI 5.84-8.15) and median PFS 2.6 months (95% CI 2.2-3.36). A dose reduction was required in 28% of patients, while 8% discontinued treatment due to toxicity. AEs reported included fatigue 81.3% (G3 16.8%), nausea 34.5% (G3 4.5%) and diarrhoea 25.5% (G3 1.8%). Neutropenia was common 50.4%, (≥ G3: 25.4%) with 4.2% cases of neutropenic fever while thrombocytopenia was less frequent 8.7% (≥ G3 1.8%). Conclusions: The OS, PFS and ORR observed in our real-world experience were consistent with the RECOURSE trial, though we noted a lower disease control rate. Overall, TAS-102 was well tolerated and the most prevalent adverse events seen in our patients were in keeping with those reported in the trial. Although severe toxicities were less frequent than the trial, we experienced higher rates of toxicity induced dose reductions and treatment cessations, which could reflect the differences between trial and real world populations. Further validation is warranted.
Safety and clinical activity of durvalumab monotherapy in patients with microsatellite instability–high (MSI-H) tumors.
Authors: Segal Neil Howard , Wainberg Zev A. , Overman Michael J. , Ascierto Paolo Antonio , Arkenau Hendrik-Tobias , Butler Marcus O. , Eder Joseph Paul , Keilholz Ulrich , Kim Dong-Wan , Cunningham David , Khleif Samir N. , Doucet Ludovic , Lee Jong-Seok , Nemunaitis John J. , Vaishampayan Ulka N. , Weiss Jared , Gao Chen , Abdullah Shaad Essa , Hollebecque Antoine
Published: January 2019

670

Background: MSI-H tumors have shown to be responsive to PD-1 inhibitor therapy. We evaluated the anti-PD-L1 mAb durvalumab in patients with MSI-H tumors, in two ongoing studies: a phase 1/2, multicenter, open-label study in patients with advanced solid tumors, and a phase 2 single-center study in patients with advanced colorectal cancer (CRC). Methods: Patients with MSI-H tumors (determined locally by immunohistochemistry or sequencing) received durvalumab 10 mg/kg IV every 2 weeks for 12 months or until confirmed progressive disease, whichever was first. Objectives were to evaluate safety and antitumor activity (per investigator-assessed RECIST v1.1). Results: As of Oct 16, 2017, 62 MSI-H patients (97% with prior anti-cancer therapy) received treatment in the multicenter study; median duration of follow-up was 29 months. Treatment-related adverse events (TRAEs) occurred in 37 patients (60%), most commonly diarrhea (15%), asthenia (11%), fatigue (11%), nausea (10%), and hypothyroidism (10%). Grade 3/4 TRAEs occurred in 2 patients (3%). There were no deaths or treatment discontinuations due to TRAEs. Objective response rates (ORR) were 23% for the total population and 22% for patients with CRC; 9 of 14 responders were ongoing at data cutoff. As of Sep 13, 2018, 11 patients with MSI-H CRC were treated in the single-center study; median duration of follow-up was 30 months. One patient discontinued treatment due to treatment-related aseptic meningitis (resolved with steroids); response rate and survival were similar to the multicenter study (Table). Conclusions: Durvalumab had a tolerable safety profile, and showed promising antitumor activity and overall survival in patients with MSI-H tumors. Clinical trial information: NCT01693562 and NCT02227667. [Table: see text]
Surgery versus surgery with adjuvant radiotherapy for T4 colon cancer.
Authors: Sebastian Nikhil , Miller Eric David , Diaz Pardo Dayssy Alexandra
Published: January 2019

673

Background: There is no randomized prospective evidence to clarify the role of adjuvant radiotherapy in localized colon cancer. Despite this, national consensus guidelines recommend that adjuvant radiotherapy be considered for patients with T4 disease. Given the lack of prospective data, the aim of this study was to evaluate the role of adjuvant radiation therapy (RT) in colon cancer using two large national databases to help to guide treatment decisions. Methods: We evaluated the association of receipt of adjuvant RT with overall survival (OS), using the National Cancer Database (NCDB) and Surveillance, Epidemiology, and End Results Program (SEER), as well as with disease-specific survival (DSS) using SEER. We analyzed cohorts of patients with histologically confirmed locally advanced T4 adenocarcinoma of the colon, who underwent oncologic surgery with or without adjuvant radiation and had at least 5 years of follow up. For the NCDB cohort, we restricted RT patients to those who received a dose of 45-60 Gy and those who received treatment within 3 months after surgery. We used nearest-neighbor propensity score matching on the basis of age, race, sex, year of diagnosis, grade, N-stage, receipt of chemotherapy, anatomical subsite, margin status, and comorbidity score. To validate our findings, using SEER, we used propensity matching using the same covariates (except comorbidity). Results: After matching of the NCDB cohort, cox regression showed no statistically significant association of adjuvant radiotherapy with OS (HR=1.08; 95% CI 0.89 - 1.30; p=0.448). Using SEER, cox regression showed no statistically significant association of adjuvant radiotherapy with OS (HR=0.9; 95% CI 0.50 - 1.63; p=0.731) or DSS (HR=0.84; 0.54 – 1.33; p=0.46). Conclusions: In summary, after comprehensively adjusting for covariates using two independent national databases, we found no statistically significant association of adjuvant RT with overall- or disease-specific survival for T4 colon cancer. These findings are limited by the retrospective nature of the data and should be tested in a prospective fashion.
Phase III randomized, placebo-controlled, double-blind study of monosialotetrahexosylganglioside in prevention of oxaliplatin-induced neurotoxicity in stage II/III colorectal cancer patients.
Authors: Li Yu-hong , Wang De-Shen , Wang Zhiqiang , Peng Jie-wen , Wang Wei , Feng Fen , Deng Yanhong , Zhang Jianwei , Wang Fenghua , Ren Chao , Wang Feng , Jin Ying , Xie Chuanbo , Tan Qiong , Chen Gong , Xu Rui-hua
Published: January 2019

674

Background: Monosialotetrahexosylganglioside (GM1) is a glycosphingolipid, which has antioxidant and neuroprotective properties. Cumulative neurotoxicity is a prominent toxicity of oxaliplatin-based therapy. This study was designed to assess the efficacy of GM1 for preventing oxaliplatin-induced neurotoxicity in colorectal cancer (CRC) patients. Methods: A total of 186 patients with stage II/III CRC undergoing adjuvant chemotherapy with modified FOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) were randomly assigned to intravenous GM1 80mg per day or placebo from day 0 to day 4 during chemotherapy. The primary end point was the rate of grade 2 or worse cumulative neurotoxicity, measured by investigator using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0. The secondary end point were the chronic cumulative neurotoxicity measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 (EORTC QLQ-CIPN20), time to grade 2 neurotoxicity by using the NCI-CTCAE or the oxaliplatin-specific neuropathy scale, the rates of acute neurotoxicity measured by a numerical analog scale ranging from 0 to 10, and the rates of dose reduction or withdrawal of both arms. Results: There were no statistically significant differences in the rate of NCI-CTCAE grade 2 or worse neurotoxicity between the study arms (GM1: 33.7% vs. placebo: 31.6%; P= 0.76). Similarly, there were no significant differences measured by EORTC QLQ-CIPN20 neuropathy scale ( P= 0.89) or additional measures of neuropathy, including measurement of the time to grade 2 neurotoxicity by using the NCI-CTCAE ( P= 0.99) or an oxaliplatin-specific neuropathy scale ( P= 0.98). In addition, GM1 did not substantially decrease oxaliplatin-induced acute neuropathy. The rates of dose reduction or withdrawal of both arms were not significantly different (GM1: 64.6% vs. placebo: 54.6%, P= 0.15). Conclusions: This study does not support using GM1 to prevent oxaliplatin-induced neurotoxicity. (NCT02251977) Clinical trial information: NCT02251977.
Patterns of adjuvant therapy use and survival outcomes in patients with rectal cancer not receiving neoadjuvant therapy in an Australian cohort.
Authors: Wilkinson Kate Jessica , Kang Sharlyn , Lim Stephanie Hui-Su , Lee Cheok Soon , Asghari Ray , Chua Wei , Ng Weng Leong , Mandaliya Hiren A. , Maloney Sarah , Chen James , Nasser Elias H. , Brungs Daniel
Published: January 2019

675

Background: Consensus international guidelines recommend the use of neoadjuvant chemo-radiotherapy in patients with stage II-III rectal cancer. Despite this, due to factors including inaccurate/under-staging, patient co-morbidities and acute presentations, a proportion will undergo up-front surgical resection. The survival benefit of adjuvant therapy is unclear in this real world, non-trial population. Methods: A retrospective analysis of patients presenting with stage II-III rectal adenocarcinoma in South Western Sydney and Illawarra Shoalhaven Health Districts, Australia, between 2006 to 2015 was performed. Data was extracted from electronic health records, with institutional ethics approval. Treatment modalities, clinicopathological, recurrence and survival data were analyzed. The primary endpoint was overall survival (OS) by treatment modality. Results: 549 patients were identified, of which 295 (54%) underwent up-front surgical resection without neoadjuvant therapy. Of this cohort, 137 (46%) had no adjuvant therapy (Group A), 103 (35%) had adjuvant chemotherapy alone (Group B), and 55 (19%) had adjuvant radiotherapy +/- chemotherapy (Group C). Receipt of any adjuvant treatment was significantly associated with improved OS (5 year OS 56 vs. 79%, HR 0.44, 95% CI 0.3 – 0.6, p < 0.0001) and recurrence free survival (5 yr RFS 25% vs. 47%, HR 0.66, 95% CI 0.5 – 0.9, p=0.01), but not cancer specific survival (5yr CSS 75 vs. 80%, HR 0.78, 95% CI 0.5 – 1.3, p = 0.30). Group B had improved OS compared to Group A (5 yr OS 56% vs. 80%, HR 0.35, 95% CI 0.22 – 0.55, p < 0.0001). There was a trend to improved OS in Group C vs. Group A (5yr OS 56.0% vs. 69.2%, HR 0.79 95% CI 0.6 – 1.01, p = 0.052). The improved OS in Group B versus Group A remained significant in multivariate analysis (HR 0.41, 95% CI 0.22 – 0.77, p = 0.005). Conclusions: Adjuvant chemotherapy improved OS in this real world cohort, and there was a trend to a benefit with adjuvant chemo-radiotherapy. However, the lack of difference in cancer specific survival suggests that this benefit may be partly driven by patient selection bias. Further exploratory analyses to identify sub-groups deriving a cancer specific survival benefit are required.
Rectal cancer treatment and outcomes in elderly patients treated with curative intent.
Authors: Kang Sharlyn , Wilkinson Kate Jessica , Brungs Daniel , Chua Wei , Ng Weng Leong , Asghari Ray , Chen James , Nasser Elias H. , Mandaliya Hiren A. , Maloney Sarah , Winn Robert , Putnis Soni , Lee Cheok Soon , Lim Stephanie Hui-Su
Published: January 2019

678

Background: There is limited information on outcomes in elderly patients with rectal cancer as they are often excluded from clinical trials. This study aimed to assess treatment patterns and outcomes in these patients. Methods: We utilised data from electronic records to identify patients aged ≥ 70 years with a histological diagnosis of rectal cancer from 2006-2015, treated in the South Western Sydney and Illawarra Shoalhaven Local Health Districts, Australia. Treatment modalities, recurrence and survival data were analysed. Results: We identified 942 patients with rectal cancer, with median follow-up of 3.4 years. 393 patients (42%) were aged ≥ 70 years. Median age of this cohort was 77 years (range 70–96 years). Elderly patients were more likely to present with locoregional disease (stage I-III, 83% vs. 75%) and more likely to receive palliative treatment only (21% vs. 16%, p = 0.0005). Of 704 patients who received treatment with curative intent, 300 (43%) were ≥ 70 years. Although clinicopathological features were similar between elderly and young patients, patients ≥ 70 years were more likely to be treated with surgery alone (56% vs. 28%, p < 0.0001), less likely to receive neoadjuvant (25% vs. 44%, p < 0.0001) or adjuvant treatments (29% vs. 55%, p < 0.0001), or be discussed in a multidisciplinary meeting (51% vs. 61%, p = 0.001). Compared to younger patients, elderly patients had a significantly poorer overall survival (HR 2.9, 95% CI 2.2 – 3.7, p < 0.0001). There were no significant differences in cancer specific survival (HR 1.4, 95% CI 0.98 – 2.0, p = 0.06) or relapse free survival (HR 0.92, 95% CI 0.7 – 1.2, p = 0.60). Conclusions: Although more elderly patients were treated with palliative intent compared to younger patients, the majority of elderly rectal cancer patients were still treated with curative intent. Most had surgery alone. Uptake of neoadjuvant and adjuvant therapy, as well as multidisciplinary involvement, was lower. Elderly patients had similar cancer-specific outcomes compared to younger patients, supporting curative intent treatment in these patients. Further analyses are underway to identify subgroups in the elderly population who benefit from trimodality therapy, and potential differences in their disease biology.
Sequencing of different targeted therapies in management of KRAS wild-type metastatic colorectal cancer: A meta-analysis.
Authors: Li Jin , Chen Gong , Fang Weijia , Tang Yongsong
Published: January 2019

679

Background: First-line (1L) antiendothelial growth factor receptor (anti-EGFR) is considered suitable in metastatic colorectal cancer (mCRC) patients. As no treatment guidelines recommend target therapy sequence in mCRC, this meta-analysis determined the optimal sequence of targeted therapies in patients with KRAS wild type (WT) mCRC. Methods: PICO framework was used to retrieve relevant studies from PubMed, Embase, Cochrane Library and Google Scholar. mCRC patients treated with 1L anti-EGFR and second-line (2L) anti -VEGF were compared with 1L anti-VEGF and 2L anti-EGFR treatment (gp. A). Patients treated with 1L anti-VEGF and 2L anti-EGFR treatment were compared with anti-VEGF in 1L and 2L (gp. B). We also compared 2L and 3L anti-EGFR therapies (gp. C). Primary and secondary outcomes of overall survival (OS) and progression free survival (PFS) were presented as hazard ratio (HR) and 95% confidence intervals (95% CIs). Objective response rate (ORR) was evaluated in terms of relative risk (RR) and 95% CI. P < 0.05 was considered statistically significant. Results: We identified nine studies for this analysis including 1478 KRAS WT mCRC patients. In gp. p A (three studies; two retrospective and one post-hoc analysis; 450 patients), 1L anti-EGFR and 2L anti-VEGF treatment had a significantly higher OS (HR 0.83, 95% CI 0.53-1.32; p = 0.0022) and PFS (HR 0.85, 95% CI 0.76- 0.96; p = 0.0081) than 1L anti-VEGF and 2L anti-EGFR. Comparison in gp. B (n = 3 RCTs involving 431 mCRC KRAS WT patients) showed no significant difference in OS (HR 0.95, 95% CI 0.70- 1.29; p = 0.6897; I2 = 42.69%) and PFS (HR 1.43, 95% CI 0.83- 2.47; p = 0.1962; I2 = 81.55%) between the two lines of treatment. ORR was higher with anti-VEGF in both 1L and 2L in gp. B (RR 3.58, 95% CI 0.72- 17.85; p = 0.1191). In gp. C, indirect comparison showed similar OS with 3L and 2L anti-EGFR therapies ((3L and 2L: n = 2 studies each; HR 0.86. 95% CI 0.71-1.04; HR 0.78, 95% CI 0.51-1.20; 2L vs. 3L; p = 0.06). Conclusions: Patients with KRAS WT mCRC achieved maximum benefit with 1L anti-EGFR and 2L anti-VEGF than with 1L anti-VEGF and 2L anti-EGFR or 1L and 2L anti-VEGF. Hence, it is suggested to initiate the therapy with 1L anti-EGFR to derive the maximum clinical benefit.
Watch and wait approach following neoadjuvant chemoradiotherapy for rectal cancer patients: A single-centre experience.
Authors: Zhu Ji , Wang Jingwen
Published: January 2019

681

Background: A watch-and-wait approach for patients with clinical complete response to neoadjuvant chemoradiation could avoid the morbidity of conventional surgery for rectal cancer. Here, we report the survival outcome of patients with this strategy in our center. Methods: We retrospectively analyzed the rectal cancer patients who received neoadjuvant chemoradiotherapy since 2015 in our center. Preoperative regimen included long-course radiotherapy (50 Gy / 25 Fx) combined fluoropyrimidin–based chemotherapy concurrently. MRI and endoscopic evaluation were performed after preoperative treatment. Patients with complete tumor response were referred to the “watch-and-wait” approach and omitted the surgery. Four to six cycles of consolidation chemotherapy were performed. Patients were followed up clinically, endoscopically, and radiologically to assess for local recurrence or disease progression. Results: From January 2015 to March 2018, a total of 47 patients with rectal cancer in our center received conservative treatment following neoadjuvant therapy. The median age of the patients is 58 (53-66). The proportions of stages I to IV are 4.3%, 12.8%, 70.2%, 8.5%, respectively. After a median follow-up of 20 month, tumor regrowth occurred in five out of 47 (10.6%) patients. All local regrowth was diagnosed in the first two years, and four out of five (80%) of local regrowth was located in the bowel wall. All patients underwent salvage surgery. Distant metastasis was diagnosed in four of 47 patients (8.5%). two-year overall survival was 89.9%, and two-year disease-free survival was 76.5%. Conclusions: Organ preservation for locally advanced rectal cancer is feasible for selected patients who achieve a complete response to individualized neoadjuvant CRT. The survival of patients is not impaired with “watch-and-wait” strategy.
Determining optimal follow up for patients with anal cancer following chemoradiation.
Authors: Frazer Marissa , Yang George Q , Felder Seth , Sanchez Julian , Dessureault Sophie , Imanirad Iman , Carballido Estrella M. , Kim Richard D. , Hoffe Sarah E. , Frakes Jessica
Published: January 2019

689

Background: U.S. health care is increasingly defined by over expenditure and inefficiency. Optimizing patient follow-up is critical especially in cancers treated with high control rates. The objective of this study was to assess time to disease recurrence or toxicity in a cohort of patients with anal carcinoma in order to optimize patient care. Methods: 140 patients diagnosed with biopsy-proven, non-metastatic anal carcinoma, treated with chemoradiation utilizing IMRT, were identified from an institutional database at our high volume center. After IRB approval, a retrospective study was conducted that evaluated local recurrence (LR), distant metastasis (DM), overall survival (OS), and late ≥ grade three toxicity (LG3T) based on National Cancer Institute Common Terminology for Adverse Events version 4. Patients were followed post-treatment every three months for two years, every six months in years 3-5 then yearly thereafter with imaging per National Comprehensive Cancer Network recommendations. Results: Median age and follow up is 58 years and 27 months, respectively. Patients were staged based on AJCC 8th edition and 24 patients were stage I (17%), 55 stage II (39%) and 61 stage III (44%). The median radiation dose was 54 Gy (range: 40-62.5), and 11% of patients required a radiation break. The two year LC, DMFS, and OS were 93%, 94% and 89% and 5-year LC, DMFS, OS were 92%, 87% and 85% respectively. In total, there were 29 disease or treatment related events: LR occurred in nine patients, DM in 11 patients, and LG3T in nine patients. Overall, 62% of events occurred within year one and 77 % within two years. Stratified by event type, at two years 79% of LR, 64% of DM and 89% LG3T were identified. At the remaining follow-up points after 2 years there was an event incidence rate of 1.4%. Conclusions: The majority of recurrences/toxicities in patients diagnosed with non-metastatic anal carcinoma after chemoradiation occur within the first year, with 77% of any event occurring before year two. The data from individual time points suggest a reduction in follow-up during years 3-5 may provide adequate surveillance. Considering revisions of the current follow-up recommendations could maximize health care resources while also improving patient quality of life.
Survival of patients with metastatic HER2 positive gastroesophageal cancer treated with second-line chemotherapy plus trastuzumab or ramucirumab after progression on frontline chemotherapy plus trastuzumab.
Authors: Moser Justin , Solomon Benjamin , Nevala-Plagemann Christopher Duane , Gilcrease Glynn Weldon , Whisenant Jonathan R. , Garrido-Laguna Ignacio
Published: January 2019

69

Background: Optimal second line treatment for patients with metastatic HER2 positive gastroesophageal cancer (Her2GE) is unknown. A retrospective study has suggested continuation of chemotherapy with trastuzumab (CT), as compared to chemotherapy alone, may improve outcomes. However, CT has never been compared to the current standard second-line treatment of chemotherapy plus ramucirumab (CR). Methods: The Flatiron Health EHR-derived database, a nationally representative database comprising patient-level structured and unstructured data, curated via technology-enabled abstraction, was reviewed for patients with metastatic Her2GE who received CT in the first line setting, followed by either second line CT or CR. Survival from second line therapy (SST) and time to next therapy or death (TTNTD) were compared using Kaplan-Meier curves and Log-Rank analysis. Demographics between treatment groups were compared using standard T tests and chi-squared analysis. Results: 135 patients were identified, of whom 34 received second-line CR and 101 received CT. Median SST for patients treated with CT was 10.2 months (m) [interquartile range (IQR) 5.1-20.8] and 6.8 m (IQR 3.2-20.2) for those treated with CR, p = 0.39. Median TTNTD for patients treated with CT versus CR was 4.9 m (IQR 2.8-9.8) and 4.8 m (IQR 2.3-7.5), respectively (p = 0.53). There was no difference between patients who received CT or CR in regards to average age (63 vs. 62, p = 0.72), average duration of first-line therapy (7.8 m vs. 9.1 m, p = 0.36), or percentage of patients with ECOG > 1 (15% vs. 22%, p = 0.50). Patients who received CT were more likely to receive a multiagent chemotherapy backbone (76% vs. 3%, p ≤ 0.001). Conclusions: This data suggest a non-significant trend towards increased SST for patients treated with second line CT versus CR. Further studies are needed to clarify optimal second-line treatment for this patient population.
Predictors of treatment response in colorectal high-grade neuroendocrine carcinomas (HGNEC): A single institution experience.
Authors: Corbett Virginia , Raj Nitya Prabhakar , Kelly Virginia , Reidy Diane Lauren
Published: January 2019

690

Background: Colorectal high-grade neuroendocrine carcinomas (HGNEC) are aggressive tumors; treatment options consist of cis/carboplatin and 5FU-based chemotherapy. To date, choice of systemic therapy and sequencing of these drugs remains poorly understood. We examined clinical and molecular characteristics of colorectal HGNEC to better define predictors of response to cis/carboplatin and 5FU-based treatment. Methods: Patients (pts) with colorectal HGNEC treated at MSKCC from 1990-2018 were identified. MANEC (mixed adeno-neuroendocrine carcinoma) were excluded. Demographics, response to first- and second-line chemotherapy (by radiology report), outcomes, and molecular data (next-generation sequencing of tumor tissue), were collected. Results: 65 pts (mean age 58, 52% male) were identified, 13 (20%) with small cell carcinomas. 52 (79%) metastatic, 13 (20%) locally advanced. 27 (42%) received surgery and 11 (17%) received radiation. 56 pts received cis/carboplatin-based therapy, partial response (PR) in 18 (32%), stable disease (SD) in 4 (7%), and progressive disease (PD) in 31 (55%); 3 (5%) did not tolerate therapy. 28 pts received 5FU-based therapy, 13 PR in (46%), SD in 6 (21%), and PD in 7 (25%); 2 (7%) did not tolerate therapy. Median overall survival was 11.4 months. 21/65 (32%) pts underwent molecular sequencing of tumor; the most common alterations were KRAS 11 (52%), TP53 13 (62%), BRAF 7 (33%), APC 8 (38%), RB1 7 (33%). Most tumors (13/21, 62%) harbored alterations in genes traditionally altered in colorectal adenocarcinoma (KRAS/BRAF/APC) and in HGNEC (TP53/RB1). There was no significant difference in response to cis/carboplatin or 5FU-based chemotherapy based on location of the primary tumor (right vs. left) (p = 0.69/0.85), histologic features of the disease (p = 0.71/0.87), and for response to cis/carboplatin by molecular alterations in KRAS (p = 0.94), BRAF (p = 0.24), APC (p = 0.28), TP53 (p = 0.58), or RB1 (p = 0.28). Conclusions: Colorectal HGNEC are highly aggressive and more effective therapies are desperately needed. In this series, OS was poor. Clinical and molecular characteristics failed to predict response to cis/carboplatin and 5FU-based chemotherapy.
Disease characteristics and treatment outcomes of young colorectal cancer patients.
Authors: Parekh Hiral D. , Wang Yu , Hanayneh Wissam , Cameron Miles , Tan Sanda , Iqbal Atif , Read Thomas , Allegra Carmen Joseph , George Thomas J.
Published: January 2019

691

Background: The incidence of colorectal cancer (CRC) in young patients (< 50 years) is increasing but little is known about disease characteristics and treatment outcomes in this patient population. Methods: CRC patients diagnosed at < 50 years of age (UF institutional registry 2000-2017) constituted the IRB approved study cohort. Statistical methods included descriptive statistics, uni-variable cox proportional hazard regression model, Pearson chi-square exact and Wilcoxon rank-sum test. Results: The median age at diagnosis was 45 years (range 17-50, n = 286) with 212 (74%) diagnosed between age 40-50. One third (35.7%) of patients had rectal primary and most common histology was adenocarcinoma (ACa, 84.6%) and 20% of those had poorly differentiated tumor. More than half of patients had an advanced primary (T3/T4, 65%) and 44% had lymph node positive disease. A trend towards increased delivery of perioperative therapy was seen in early staged disease. (See table) Patients who underwent curative resections had better hemoglobin (p = 0.005) and albumin levels (Alb, p < 0.001) and lower CEA level (p < 0.001). Factors associated poor survival were low alb levels ≤ 34 g/l, advanced primary tumor (T3/T4), nodal disease (N1/N2) and presence of diffuse metastasis. For stage 4 disease, the cancer-specific survival (CSS) at 1 year was 77.2%, 3-year CSS was 46.1% and 5-year CSS was 29%; survival was better (HR = 0.4; 95% CI 0.2-0.6, p < 0.001) among patients who underwent metastatectomy. Conclusions: Our data suggests that younger CRC patients were more likely to be managed in an aggressive manner with a higher proportion of early stage patients receiving perioperative therapy. A suggestion of an improved CSS was seen in advanced stage disease even with similar prognostic factors. Review of larger datasets are warranted. [Table: see text]
Organ preservation in rectal cancer patients treated with total neoadjuvant therapy.
Authors: Jimenez-Rodriguez Rosa Maria , Quezada-Diaz Felipe Fernando , Hameed Irbaz , Patil Sujata , Smith Jesse Joshua , Garcia-Aguilar Julio
Published: January 2019

692

Background: Retrospective case series suggest that watch-and-wait (WW) is a safe alternative to total mesorectal excision (TME) in selected patients with a clinical complete response (cCR) after chemoradiotherapy (CRT). Because treatment strategies vary widely and total numbers of patients treated at different institutions have not been reported, the proportion of rectal cancer patients who can potentially benefit from WW is not known. Here, we report the results of a treatment strategy incorporating WW in a cohort of rectal cancer patients treated with total neoadjuvant therapy (TNT). Methods: Consecutive patients with stage II/III (MRI staging) rectal adenocarcinoma treated with TNT from 2012 to 2017 by a single surgeon were included. TNT consisted of mFOLFOX6 (8 cycles) or CapeOX (5 cycles) either before or after CRT (5600 cGy in 28 fractions with sensitizing fluorouracil or capecitabine). Tumor response was assessed with a digital rectal exam, endoscopy, and MRI according to predefined criteria. Patients with a cCR were offered WW, and patients with residual tumor were offered TME. WW and TME patients were compared based on intention to treat, using the chi-square or rank sum test. Relapse-free survival (RFS) was evaluated by Kaplan-Meier analysis. Results: A total of 109 patients were identified. One patient died during CRT. Of the 108 patients, 64 (59%) had an incomplete clinical response; 4 of the 64 patients declined surgery or had local excision, and 60 underwent TME. The remaining 44 patients (41%) had a cCR and underwent WW. On average, patients in the WW group were older and had smaller, more distal tumors. Median radiation dose, number of chemotherapy cycles, number ofadverse events, or length of follow-up (28 months) did not differ between the TME and WW groups. Five (11%) of the 44 WW patients had local tumor regrowth, at a median of 14 (4–25) months after TNT; 2 of the 5 also had distant metastasis. Six (10%) of the 60 TME patients had a pathological complete response. RFS did not differ between the TME and WW groups (log rank P= 0.09). Conclusions: Approximately 40% of patients with stage II/III rectal cancer treated with TNT achieve a clinical complete response and can benefit from a WW approach with the aim of preserving the rectum.
Gastrostomy tube for nutrition and bowel obstruction in patients with advanced malignancy: Less is more.
Authors: Gauvin Gabrielle , Do-Nguyen Chi Chi , Selesner Leigh T , O'Halloran Eileen , Lou Johanna , Collins Molly , Farma Jeffrey M.
Published: January 2019

700

Background: Malnutrition and malignant bowel obstruction (MBO) are common consequences of advanced malignancy. Both lead to a poor prognosis, frequent hospitalizations, and have a negative impact on quality of life. The aim of this study is to explore gastrostomy tube (g-tube) placement practices to better define the role of g-tube role in advanced malignancy. Methods: Patients who underwent g-tube placement at our tertiary cancer care center between 2013 and 2017 were included in this study. Patients’ demographics, diagnosis, procedures, postoperative course, and clinical data were collected. Complications and survival were used as endpoints. Results: Two hundred forty-two cancer patients with an average age at diagnosis of 61 years (range 21-94) underwent g-tube placement for nutrition (76.4%), decompression (MBO) (22.7%), or both (0.8%). Active treatment within 3 months of g-tube insertion was seen in 37.8% of the nutrition group versus 29.1% in the MBO group (p = 0.208). Successful insertion was achieved in 96.8% of patients, but nine patients required more than one method of insertion attempt. In the nutrition group, successful method of insertion was 88.1% in interventional radiology, 8.1% in operating room, and 3.8% in endoscopy suite, compared to 81.8%, 14.5%, and 3.6% for the MBO group, respectively (p = 0.426). Post-placement complications were significantly less common in the MBO group compared to the nutrition group (24.1 vs. 54.3%, p < 0.001). Consultation pattern in the MBO group revealed that 45.5% had a palliative care consult, 56.4% were seen by social work, and 47.3% went to hospice. Survival in the MBO group was significantly shorter than in the nutrition group at 30 days (52.7 vs. 90.3%, p < 0.001), 1-year (54.6 vs. 5.9%, p<0.001), and three years (24.1 vs 1.8%, p = 0.001) after g-tube placement. Conclusions: In our experience, most patients who undergo g-tube insertion are not receiving active treatment and a large proportion of patients who receive a decompressive g-tube have a life expectancy of less than a month. These findings will inform the next step of our study: creating a discussion tool to coordinate better care and interventional decision making for patients with advanced malignancy.
Total neoadjuvant therapy compared with standard therapy in locally advanced rectal cancer: A systematic review and meta-analysis.
Authors: Manthravadi Sashidhar , Sun Weijing , Saeed Anwaar , Baranda Joaquina Celebre , Kasi Anup
Published: January 2019

709

Background: Standard therapy of locally advanced rectal cancer (LARC) includes concurrent chemoradiotherapy (CRT) followed by surgery and adjuvant chemotherapy (CT). An alternative strategy known as Total Neoadjuvant Therapy (TNT) involves administration of CRT and CT prior to surgery with the goal of delivering uninterrupted systemic therapy to eradicate micrometastases. A comparison of these two approaches has not been reviewed previously. Methods: Following PRISMA guidelines, a systematic review of PubMed and Web of Science was performed from inception through September 2018 to identify studies which compared TNT with CRT in LARC. The outcomes of interest were pathologic complete response rates (PCR), sphincter-preserving surgery rates, ileostomy rates, disease-free survival (DFS) and overall survival (OS). Summary hazard ratios (HR) with 95% confidence intervals (CI) were estimated using a random effects model and heterogeneity was estimated using the inconsistency index (I2). Results: After reviewing 2,163 reports, 5 studies which compared CRT and TNT were selected for inclusion. These were reported from Europe and the United States and included a total of 1,134 patients of whom 552 received TNT. The pooled prevalence of PCR was 32.4% (range 17-28%) in the TNT group and 22.3% (range 4-21%) in the CRT group. In a meta-analysis of five studies, TNT was associated with a higher chance of achieving a pathologic complete response (OR 1.92; 95% CI 1.44- 2.57, I2= 22%). Recipients of TNT also had higher odds of receiving sphincter-sparing surgery (5 studies, OR 1.92; 95% CI 1.44- 2.57, I2= 0%) and lower odds of requiring an ileostomy (2 studies, OR 0.72; 95% CI 0.54- 0.96, I2= 0%). Only one study presented data on DFS and noted improved DFS in patients who received TNT (OR 0.72; 95% CI 0.54- 0.96). The impact of TNT relative to standard therapy on overall survival was not reported. Conclusions: Total Neoadjuvant Therapy is a promising strategy in locally advanced rectal cancer, with superior PCR rates compared to standard therapy. However, the long term impact on disease recurrence and overall survival remain unclear. These are best be studied in a prospective randomized clinical trial.
Elucidating the pathogenesis of esophageal adenocarcinoma through meta-analysis of public data.
Authors: Khorfan Kamal , Aljabban Jihad , Syed Saad , Salhi Hussam , Adejare Aderinola , Suara Habeeb , Allarakhia Zahir , Panahiazar Maryam , Hadley Dexter
Published: January 2019

71

Background: Esophageal adenocarcinoma (EAC) is the sixth most common cause of cancer-related deaths worldwide. It commonly arises in the setting of reflux disease and Barett’s esophagus. It remains incurable and holds a poor prognosis. Dissecting the genetic signature of EAC can pave new therapeutic avenues. Methods: We employed our Search Tag Analyze Resource (STARGEO) platform to conduct meta-analysis using the National Center for Biotechnology’s (NCBI) Gene Expression Omnibus (GEO). We tagged 151 tumor samples from EAC patients and 62 normal esophageal samples as a control. We then analyzed the signature in Ingenuity Pathway Analysis, restricting genes that showed statistical significance (p < 0.05) and an absolute experimental log ratio greater than 0.15 between tumor and control. Results: Our analysis revealed granulocyte adhesion and diapedesis and FXR/RXR signaling as top canonical pathways. TGFB1, TNF, and beta-estradiol were top upstream regulators with predicted activation. TGFB1 and TNF expression have been correlated with poor prognosis in EAC. Also, beta-estradiol has tumorigenic activity in several cancers but has not been investigated in EAC. Among the top upregulated genes were oncogenic genes such as tetraspanin 8, the antiapoptotic factor OLFM4, and the protease cathepsin E (CTSE). SPINK1, a trypsin inhibitor with recently suggested role in cancer, and the choline transporter SLC44A4, a drug target for pancreatic cancer, were also upregulated. The most downregulated genes included alcohol dehydrogenase 7, associated with EAC in alcohol-drinkers, and the pro-apoptotic gene CRCT1. We also found downregulation of the serine peptidase inhibitor SPINK7. SPINK7 is involved in maintaining epithelial-barrier integrity and is implicated in eosinophilic esophagitis pathogenesis. Lastly, there was downregulation of the candidate tumor suppressor gene transglutaminase 3. Conclusions: Despite screening efforts, EAC incidence and mortality continues to increase as does the need for better treatment. This meta-analysis defines the significant gene expression changes within causal disease processes to provide markers for detection, prognostic insight, and therapeutic value for EAC.
Nodal retrieval and short-term outcomes of robotic and laparoscopic colectomies for colon cancer.
Authors: Nguyen Trang , Stern Stacey , Dehal Ahmed , Vuong Brooke , Bilchik Anton J.
Published: January 2019

713

Background: It is debatable whether robotic colectomies is advantageous over laparoscopic colectomies for colon cancer (CC). We aim to evaluate oncologic and perioperative outcomes between robotic and laparoscopic colectomies in a national database. Methods: The National Cancer Database was queried from 2010-2014 for patients with resectable (stage I-III) CC. Lymph node (LN) retrieval, length of stay (LOS), perioperative outcomes and OS were analyzed based on type of surgery: right colectomy vs. left colectomy and robotic (ROBO) vs. laparoscopic (LAP). Results: 61,903 patients met inclusion criteria. There was no difference in inadequate LN retrieval (< 12 LN), or short-term mortality between ROBO and LAP groups. There was a significant decrease in conversion to an open operation and LOS for ROBO vs. LAP groups as well as increased 5 year OS (Table). ROBO colectomies increased four-fold over 5 years. About half were done at community hospitals (56%) and at low ROBO volume hospitals (47.2%). Inadequate LN retrieval in the ROBO group was greater at low volume centers (9.2%) compared to high volume centers (12.3%) (p < 0.0001) as well as at community hospitals (12.2%) compared to academic hospitals (8.5%) (p=0.0003). Conclusions: This population analysis showed that robotic colectomies was associated with equivalent short-term outcomes and LN retrieval as laparoscopic colectomies. However, half of robotic colectomies were done at community hospitals or low volume hospitals, where the rate of inadequate LN retrieval was higher than at academic hospitals or high volume centers. As robotic colectomies increases, it is important that technology is implemented judiciously so that oncologic outcomes are not compromised. [Table: see text]