bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of multidisciplinary management in the diagnosis and treatment of neuroendocrine tumors (NET).
Authors: Sandhu Gurprataap Singh , Krishnamurthy Anuradha , Weiss Reed , Meguid Cheryl Lauren , Davis S. Lindsey , Leong Stephen , Leal Alexis Diane , King Gentry Teng , Purcell William T. , Goodman Karyn A. , Head Lia , Schefter Tracey E. , Johnson Thor , Ahrendt Steven Arthur , Brown Matthew , Gleisner Ana , Schulick Richard D. , McCarter Martin , Messersmith Wells A. , Lieu Christopher Hanyoung 
Published: January 2019

629 Background: The incidence and prevalence of NETs is increasing and diagnosis and pathologic evaluation of NETs is complex. Given the new advances in local and systemic therapies, multidisciplinary management models have been suggested to assist in treatment decisions. However, scientific data showing definite change in management with multidisciplinary clinic (MDC) review is lacking. We aim to address this need in this study. Methods: 113 GI-NET patients from 2012-18 were reviewed from a dedicated MDC where patients are seen simultaneously by multiple subspecialties, and data on patient characteristics, radiology, tumor pathology and treatment strategies were collected. Change in diagnosis was defined as any change in radiographic or pathologic findings that resulted in a change in the tumor type, grade, site or stage of cancer. Change in management was defined as any recommended change in treatment approach for NETs compared to the prior treatment plan. For patients who did not have a prior treatment plan or were seen directly at MDC, a change of management was considered as yes only if there was a change in diagnosis post MDC. Results: The mean age of patients evaluated was 61, with locally advanced or metastatic disease seen in 81% of patients. Small bowel and pancreatic NETs were the most common primaries (36% each). Significant proportion of NETs were well-differentiated (72%) with < 2 mitosis/10 HPF (47.3%) and Ki-67 of < 3% (36%). Patients were referred to MDC at an average of 2.5 years from diagnosis, with 23% having the MDC as their first visit. 40% had prior resection of primary, 25% were on somatostatin analogues (SSAs) previously and 9% of patients had received prior liver directed therapy (LDT). A significant proportion of patients had change in diagnosis post MDC evaluation: change in site (7%), stage of disease (7%), tumor type (3.5%) and grade (0.1%). A change in management was recommended in 50% of patients, with SSAs recommended in 43.8%, surgery in 25.4% and LDT in 17.5% of the patients. Conclusions: The use of a dedicated MDC to manage NETs had a substantial impact in change in management in a significant percentage of patients evaluated. MDC care for patients diagnosed with NET is recommended for optimal management.
Early tumor shrinkage and depth of response as predictors of favorable treatment outcomes in patients with metastatic colorectal cancer treated with FOLFOX/FOLFIRI plus cetuximab.
Authors: Somashekhar S.P. , Rauthan Amit , Rajgopal Ashwin K , C Rohit Kumar 
Published: January 2019

631 Background: Early tumor shrinkage (ETS) and depth of response (DoR) predict overall survival (OS) in first-line chemotherapy + anti-EGFR monoclonal antibodies in KRAS wild-type metastatic colorectal cancer (mCRC). This association and the predictive accuracy of response measurements were investigated in the first-line setting for FOLFOX/FOLFIRI plus cetuximab. Methods: We performed a study of FOLFOX/FOLFIRI plus cetuximab as first-line treatment in Indian patients with KRAS wild-type mCRC. The primary endpoint was response rate (RR), and secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Radiologic assessments at week 8 were used to calculate the relative change in the sum of the longest diameters of the target lesions. Cox regression models analysis investigated associations between ETS and overall survival (OS) and progression-free survival (PFS). Results: Sixty (78.9 %) of 76 patients had ETS, which was associated with prolonged PFS and OS. Both ETS and DoR were able to predict survival as accurately as RECIST response. Both ETS and DoR were associated with PFS and OS at the univariate analyses and in the multivariate models stratified for other prognostic variables. In the study patients, the RR, median PFS, and OS were 68.4 %, 13.1 months, and 30.6 months, respectively. Median DpR was 52%. The DpR correlated with OS as well as PFS. FOLFOX plus cetuximab was active as a first-line, with no major toxicities. Conclusions: Our prospective evaluation of chronological tumor shrinkage showed that ETS and DpR correlate with outcomes in patients with KRAS wild-type mCRC who receive cetuximab-based chemotherapy. Achieving rapid and deep tumor shrinkage consistently delays tumor progression and prolongs survival in patients treated with first-line chemotherapy plus cetuximab. ETS is a promising and valuable end point for clinical trials’ design deserving further investigation.
A retrospective study of a dexamethasone-sparing strategy of preventing acute and delayed emesis caused by CapeOx regimen with aprepitant for colorectal cancer.
Authors: Nakatsuka Miho , Sakai Daisuke , Murachi Yasushi , Nishida Naohiro , Kudo Toshihiro , Kimura Akie , Otsuru Toru , Takahashi Hidekazu , Miyoshi Norikatsu , Haraguchi Naotsugu , Matsuda Chu , Kadowaki Hiroko , Yamamoto Tomoya , Kuritani Yoshitaka , Mizushima Tsunekazu , Doki Yuichiro , Mori Masaki , Miwa Yoshihior , Satoh Taroh 
Published: January 2019

632 Background: CapeOx therapy which is combination with oxaliplatin (L-OHP) and capecitabine is one of the standard treatments for first line chemotherapy for unresectable colorectal cancer, or for postoperative adjuvant chemotherapy for stage III colon cancer. L-OHP-based regimen is classified as moderately emetogenic chemotherapy. In the SENRI trial which we previously conducted as phase III trial, aprepitant, an NK-1 antagonist, showed the efficacy for prevention of emesis against L-OHP. On the other hand, even when in highly emetogenic chemotherapy, it is reported that dexamethasone after day 2 could be spared. Methods: We retrospectively reviewed chemo-naive 94 patients with colorectal cancer who underwent CapeOx therapy at our institution from April 2012 to March 2017. We assessed the relationship between emesis during the first cycle of CapeOx (day1-5) and the use of dexamethasone on day 2-3. Results: 10 patients underwent CapeOx plus bevacizumab, and 84 underwent CapeOx. All patients received 5-HT3 receptor antagonist (palonosetron: 87, granisetron: 7). 50 patients received aprepitant on days 1-3 and dexamethasone on day 1 (APR+D1 group). 22 patients received aprepitant on days 1-3 and dexamethasone on days 1-3 (APR+D3 group). 15 were dexamethasone on days 1-3 without aprepitant (D3 group), and 7 were dexamethasone only on day 1 without aprepitant (D1 group). Acute complete response (CR; no vomiting and no rescue anti-emetics) rates were 100% in any groups. Delayed CR rate was 56% in APR+D1 group, 86% in APR+D3 group, 53% in D3 group, and 29% in D1 group, respectively. In multivariate linear regression with aprepitant, there was a significant difference in presence of dexamethasone (p = 0.028). Conclusions: Acute emesis could be prevented by even only 1-day administration of dexamethasone when combined with the triplet prophylactics. However, in order to sufficiently prevent delayed emesis induced by L-OHP, it was suggested that addition of DEX on days 2 and 3 might be better.
Evaluation of the re-introducing FOLFOX or XELOX ± bevacizumab in relapsed colorectal cancer patients treated with oxaliplatin as adjuvant chemotherapy (REACT study).
Authors: Iwamoto Shigeyoshi , Kotaka Masahito , Ikumoto Taro , Sakai Daisuke , Kudo Toshihiro , Tsuji Akihito , Ide Yoshihito , Fukunaga Mutsumi , Konishi Ken , Sugimoto Naotoshi , Kurata Takayasu , Kanazawa Akiyoshi , Satoh Taroh , Yamanaka Takeharu , Tomita Naohiro 
Published: January 2019

634 Background: Chemotherapy in relapsed colon cancer patients (pts) treated with oxaliplatin as adjuvant chemotherapy is under debate. REACT study aimed to investigate the efficacy of re-introducing FOLFOX or XELOX ± bevacizumab therapy for recurrent colorectal cancer pts after adjuvant chemotherapy including oxaliplatin. Methods: Pts with past history of adjuvant chemotherapy including oxaliplatin (FOLFOX, XELOX or SOX) with a cumulative dose of more than 400 mg/m2, and recurrence observed by imaging after more than 6 months post adjuvant chemotherapy participated in this trial. Primary endpoints were response rate (RR) and disease control rate (DCR). Key secondary endpoints were progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS) and safety. Results: A total of 31 pts were enrolled between Oct 2012 and Oct 2016. Of 29 eligible pts, 7 received FOLFOX ± bevacizumab, and 22 received XELOX ± bevacizumab. 28 of the pts received bevacizumab. The RR was 66.7% (95% CI, 46.0-83.5) and the DCR was 88.9% (95% CI, 70.8-97.6). The RR for oxaliplatin free-interval was 100.0% (n = 4, 95% CI, 39.8-100.0) in 6 to 12 months, 60.9% (n = 25, 95% CI, 38.5-80.3%) over 12 month, respectively. Median PFS, TTF and OS were 10.9 months (95% CI, 7.0-19.0), 6.3 months (95% CI, 2.8-8.0) and 29.1 months (95% CI, 20.3-53.3). The most common grade 3 or 4 adverse event was hypertension (19.4%). Grade 3 or worse peripheral sensory neuropathy developed only two pts (6.5%). Allergic reactions occurred in 12.9% of the pts, with one (3.2%) grade 3 episode. There were no other severe treatment-related adverse events. Conclusions: Re-introduction of oxaliplatin was feasible and achieved high RR or DCR in after more than 6 months post adjuvant chemotherapy including oxaliplatin. Clinical trial information: UMIN000006523.
Validation of cost-effectiveness of trifluridine/tipiracil versus best supportive care and regorafenib for previously treated metastatic colorectal cancer in the UK using phase IIIb PRECONNECT early access clinical trial data in the real world setting.
Authors: Sabater Javier , Ralph Lewis , Batteson Rachael , McCarthy Grant , Wex Jaro , Moreno Vera Shanti Ricardo , Becquart Martin , Mounedji Nadjat , Taieb Julien , Peeters Marc , Falcone Alfredo 
Published: January 2019

639 Background: Trifluridine/tipiracil (FTD/TPI) is indicated and recommended for the treatment of previously treated metastatic colorectal cancer (mCRC). Previous evaluations used pooled clinical evidence from the Phase III (RECOURSE) and Phase II trials to model cost-effectiveness, but FTD/TPI specific utilities were not available and alternative data sources were used. The aim of this study was to utilize EQ-5D data from an ongoing Phase IIIb trial (PRECONNECT) within an updated cost-effectiveness model to validate health-related quality of life (HRQoL) outcomes for mCRC patients receiving FTD/TPI. Methods: EQ-5D-3L data from PRECONNECT trial were analyzed with UK utility tariff applied. Pre- and post-progression health state utilities were estimated using a linear mixed effects regression model. Indirect comparison versus regorafenib was based on evidence from the CORRECT trial. Utilities and UK costs (GBP, 2018) were then implemented into the existing economic model. Results: Mean pre-progression and post-progression utilities were 0.72 and 0.59, respectively, with discounted incremental quality adjusted life years gain of 2.1 months versus best supportive care (BSC) and 0.8 versus regorafenib. Use of FTD/TPI based on PRECONNECT data, as in the previous analysis, was associated with improved mean survival pre-progression (by 1.8 months) and post-progression (by 1.4 months) for the total OS gain of 3.2 months versus BSC. The mean OS gain versus regorafenib was 1.4 months. Updated cost-effectiveness analysis using PRECONNECT derived inputs showed that results remained broadly unchanged with a negligible increase in ICER from £51,589 to £51,792 (£51,101 in the probabilistic sensitivity analysis) when compared to BSC, while FTD/TPI remained dominant (more effective and less costly) versus regorafenib. Conclusions: New HRQoL data from the PRECONNECT study collected in a real-world setting validated previous HRQoL inputs used to model cost-effectiveness of FTD/TPI in previously treated metastatic colorectal cancer. Clinical trial information: NCT03306394.
Outcomes following stereotactic body radiotherapy (SBRT) in locally recurrent rectal cancer (LRRC) in a previously irradiated pelvis.
Authors: Smith Thomas , O'Cathail Sean , Tsang Yatman , Harrison Mark , Hawkins Maria A 
Published: January 2019

640 Background: Management of LRRC is challenging. There is no consensus regarding the best approach for patients not suitable for exenteration. Hyperfractionated re-irradiation is associated with > 10% grade 3 toxicity and it is demanding for patients and department. Here we report initial outcomes of an inoperable cohort treated with SBRT. Methods: A prospective nationally maintained database for SBRT re-irradiation was interrogated. Eligibility criteria were pelvic recurrence in a previously irradiated colorectal cancer, not eligible for exenteration, > 6 mo disease free survival, > 6mo from previous RT, ≤ 3 metastases, PS 0-1. SBRT dose of 30Gy in 5 fractions in < 10 days was specified. Every 3 mo toxicity was assessed using the CTCAE v4.0, QoL using the EQ5D, respectively and imaging was undertaken. Median progression free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Results: 28 patients with 33 separate pelvic lesions were treated between Oct 2015-June 2018. The median age was 64 years (range 36-84). 27/28 had received 45-50.4Gy in 25-28F with concurrent Capecitabine, 1/28 received 25Gy/5F, all followed by surgery. Combining SBRT, the cumulated effective dose received was >100Gy10. The median GTV volume was 14.9cc (range 0.47-121.73cc). All completed the SBRT. There were minimal symptoms at baseline pain = 7, urinary = 3, GI = 3, nerve = 1. 48% grade 1 or grade 2 acute toxicity was reported at 6 weeks, with 25% grade 1 or grade 2 late toxicity, but no grade 3 toxicities reported with a median follow up of 10 months (range 2-30). There was an 81% local control rate with a median PFS of 12.2 months (95% CI 4.0-20.5) and a 2-year OS of 70.4% (95% CI 49.0-100). 28% (8/28) solely progressed out of field. Conclusions: Acute toxicity is minimal in this cohort of patients with initial excellent local control. Follow-up is continued. SBRT appears effective and convenient for patients who are non-surgical candidates with pelvic recurrence and offers the opportunity for local and symptom control, whilst deferring systemic treatment.
Improving clinician confidence and practice behavior on the therapeutic management of microsatellite-instability high (MSI-H) gastrointestinal (GI) cancers.
Authors: Jaganathan Hamsa , Roc Anne , Turell Wendy , Broaddus Russell , Overman Michael J. 
Published: January 2019

641 Background: With recent advances of immunotherapy and updates to practice guidelines, clinicians may be challenged in applying and managing the outcomes of new treatment standards for their patients with MSI-H GI cancers. To address this need, a one-hour education session was provided to clinicians and learner responses were evaluated to determine the areas of improvement in the therapeutic management of MSI-H GI cancers. Methods: PlatformQ Health developed and executed a 1-hour online CME program on MSI-H GI cancers, which was broadcast live in March 2018 and offered online for 6 months. The program attracted a total of 439* learners. Survey-based evaluations before (n = 338) and after education (n = 147) targeted self-reported clinician data on confidence, practice behaviors, knowledge, and competence. Results: A self-reported survey (n = 56) conducted 8-12 weeks after education reported that 50% of learners were more confident in managing patients with MSI-H GI cancers, 41% in following NCCN practice guidelines for MMR/MSI testing, and 34% in utilizing checkpoint inhibitors for MSI-H GI tumors. Competence on selecting an appropriate treatment for a patient with MSI-H colon cancer significantly improved between pre- and post-education (52% and 63%, respectively; p < 0.001). Significant improvements in knowledge regarding the latest immunotherapy data (33% at baseline to 54% post-education; p < 0.001) and available methods for determining MMR/MSI-H status (18% at baseline to 41% post-education; p < 0.001) were also observed. Conclusions: Outcomes results from education demonstrate learner improvements on facets of management of MSI-H GI cancers. Based on the analysis, further education is needed, particularly in areas of management of immune-related side effects in line with recent ASCO and NCCN guidelines, tools for determining dMMR/MSI-H status, and deciding on optimal treatment based on tumor status. *As of September 10, 2018, data collection is ongoing.
Temporal trends and disease characteristics associated with total neoadjuvant therapy (TNT) usage.
Authors: Babar Laila , Bakalov Veli , Abel Stephen , Finley Gene Grant , Raj Moses S. , Monga Dulabh K. , Kirichenko Alexander V. , Wegner Rodney E 
Published: January 2019

642 Background: Neoadjuvant chemoradiotherapy (nCRT) followed by resection and postoperative multi-agent chemotherapy (maChT) is the standard of care for locally advanced rectal cancer (LARC). Using this approach, maChT administration is delayed several months, leading to concern for high rates of distant failure. To reduce the rate of systemic failure, a novel treatment approach known as total neoadjuvant therapy (TNT) has been increasingly employed, in which patients receive both maChT and nCRT prior to resection. We utilized the National Cancer Database (NCDB) to examine temporal trends in TNT usage, as well, as any potential effect on survival. Methods: We queried the NCDB for patients diagnosed with LARC (Stage II-III) from 2004–2015 treated with nCRT or TNT. TNT was defined as maChT initiated ≥ 90 days prior to the start of nCRT. Overall survival (OS) was calculated from the date of diagnosis to the date of last contact or death using Kaplan Meier curves to present the cumulative probability of survival, with log-rank statistics used to assess statistical significance between groups. Multivariable cox regression was used to identify predictors of survival and propensity score analysis was used to account for indication bias. Results: We identified 9,066 eligible patients, with 8,812 and 254 patients receiving nCRT and TNT, respectively. Nodal involvement and Stage III disease were predictive of TNT use, as well as, treatment in in more recent year. TNT and nCRT had similar 5-year survival, 76% and 78%, respectively. MVA identified age > 58, increased income, urban location, academic treatment facility, and lower co-morbidity score as predictors of worse OS. Multivariable analysis with propensity score demonstrated increased age, higher comorbidity score, higher grade, African American race, and gender as predictive of worse OS. Conclusions: Our data demonstrates a trend toward increasing TNT use, particularly in patients with greater nodal involvement or clinical stage. Despite worse disease characteristics, patients treated with TNT had similar survival to those receiving standard nCRT. Randomized trials are underway to further define the clinical benefit of TNT.
Cost and effectiveness of genetic testing in metastatic colorectal cancer (mCRC) at Montefiore Medical Center (MMC).
Authors: Ashai Nadia , Stuart Matthew , Rao Devika , Mejia Saldarriaga Mateo , Zhang Wei , Huang Renee , Narang Rahul , Chuy Jennifer W. , Kaubisch Andreas , Goel Sanjay , Halmos Balazs , Rajdev Lakshmi 
Published: January 2019

643 Background: Upfront testing for MSI, and mutations in KRAS, NRAS, and BRAF is recommended. The most cost-effective way of obtaining this information remains unclear. We examined cost of broad next generation sequencing (NGS), in comparison to hotspot (HT) and individual target (IT) testing in patients with mCRC with Medicare (MC) and commercial insurance (CI) at MMC. As a surrogate of effectiveness, we hypothesize that patients with NGS are more likely to enroll in clinical trials. Methods: Cost of individual and hotspot tests were derived from known reimbursement rates with insurances affiliated with MMC. Due to ongoing changes in current procedural terminology for NGS, we used known reimbursement amounts from our patients. We applied these costs to a model population of 1,000,000 people. We then evaluated clinical trial enrollment of patients who had either NGS or hotspot/individual testing. Results: MC costs for IT, HT, NGS testing were $1,504, $752, and $4,680 respectively. CI costs were $1,910, $814, $2,366 for IT, HT, and NGS testing respectively. When applied to our model population, NGS cost $914,604 and $1,131,016 more than individual and hot spot testing respectively for MC patients, and $21,432 and $72,924 more for CI patients. Analysis of effectiveness included 136 patients, wherein 8% of those with NGS (n = 5/61) were enrolled in clinical trials as a result of testing compared to 1% of those with HT/IT (n = 1/75). Conclusions: Broad spectrum NGS costs more than individual or hot spot testing in mCRC. However, patients with NGS testing were more likely to be enrolled in clinical trials, suggesting the need for studies to further evaluate ideal testing modality. [Table: see text]
Predicting imminent disease progression in advanced colorectal cancer by a machine-learning algorithm.
Authors: Kogan Yuri , Shannon Shmuel , Taub Eldad , Kleiman Marina , Elishmereni Moran , Agur Zvia 
Published: January 2019

645 Background: In advanced cancers, predicting disease progression just before its clinical manifestation enables an earlier switch to the next treatment line, preventing deterioration in the patient's state and potentially improving survival. Yet, given the ambiguity of current tumor markers in alerting to progression, physicians are unable to forecast this key event. We developed a diagnostic algorithm for announcing an approaching disease progression in late-stage colorectal cancer (CRC) patients by processing continuous carcinoembryonic antigen (CEA) input. Methods: Longitudinally measured CEA data of advanced CRC patients treated by standard 1st line chemotherapies, collected from 2 clinical trials (projectdatasphere.org), served for algorithm development by machine-learning and training assisted by receiver-operating-characteristic (ROC) analysis and correlation tests. Performance was validated by cross-validation techniques. Results: CEA and response evaluations of 489 CRC patients (median follow-up time: 168 days) were processed by the algorithm, predicting disease progression with 57% sensitivity (100/175 progression events) and 88% specificity (21/175 false positives). Positive and negative predictive values, accuracy and Cohen’s kappa were 64%, 84%, 79% and 0.46, respectively. The algorithm’s predictive power was superior to that of standard statistical analyses of these CEA data (e.g., ROC). Conclusions: Our study offers a new approach to using tumor markers as prognosticators. The algorithm-amplified ability of CEA to predict progression in CRC complements our recent findings in lung cancer, where integration of CEA and 4 other markers provided 66% sensitivity in predicting progression, surpassing the low capacity of each separate marker. Conceivably, future algorithm-integration of multiple markers in CRC may also exceed the limited signal of a single marker. Clinical use of our algorithm, amplifying weak marker signals of imminent progression, should allow physicians to reliably harness tumor markers for improving treatment and potentially extending survival in cancer patients.