bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of socioeconomic factors on outcomes of patients with locally advanced rectal cancer (LARC).
Authors: Gotfrit Joanna , Thangarasa Tharshika , Marginean Horia , Dudani Shaan , Goodwin Rachel Anne , Tang Patricia A. , Monzon Jose Gerard , Dennis Kristopher , Cheung Winson Y. , Vickers Michael M.
Published: January 2019

612

Background: Patients with rectal cancer may experience disparities in outcomes due to various socioeconomic (SES) factors. We assessed the impact of SES factors on outcomes in patients with LARC who received neoadjuvant chemoradiation (nCRT) and surgery (Sx) in three Canadian provinces. Methods: Associations between clinical variables, demographics, community characteristics (2015 Canadian Census data), distance and time to the nearest cancer center (mapping software), and outcomes were evaluated. Results: 1,098 patients were included (Table 1). Median follow-up time was 67.8 months. The 5-year survival rate was 0.80 (95% CI 0.77-0.82). Factors predictive of disease-free survival in univariate analysis (UVA) included age, worse performance status (PS), driving time > 1 hour, median community income, and driving distance > 100 km. Factors that remained significant in multivariate analysis (MVA) included age (HR 1.01; 95% CI 1.00-1.02; p = 0.01), worse PS (HR 1.30; 95% CI 1.01-1.68; p = 0.04) and driving time > 1 hour (HR 1.31; 95% CI 1.01-1.71; p = 0.04). Factors predictive of overall survival in UVA included age, worse PS, driving time to the cancer centre > 1 hour, median community income, and community proportion with post-secondary education. Factors that remained significant in MVA included age (HR 1.03; 95% CI 1.02-1.04; p < 0.001), worse PS (HR 1.41; 95% CI 1.03-1.94; p = 0.03), and median community income (HR 1.00; 95% CI 1.00-1.00; p = 0.05). Conclusions: Outcomes of patients with LARC undergoing nCRT are significantly associated with driving time to the nearest cancer centre and community household income. Further efforts to understand and reduce these socioeconomic disparities are warranted. [Table: see text]
A randomized phase II study comparing oral S-1 plus 24-hour infusion of irinotecan (Iri) and bevacizumab (Bev) with FOLFIRI plus bevacizumab in patients with metastatic colorectal cancer (MCRC).
Authors: Sadahiro Sotaro , Suzuki Toshiyuki , Tanaka Akira , Okada Kazutake , Saito Gota , Miyakita Hiroshi , Ogimi Takashi , Chan Lin Fung
Published: January 2019

613

Background: FOLFOX or FOLFIRI plus Bev is a first-line treatment for MCRC. Recent studies have confirmed that oral S-1 combined with Iri and Bev is equivalent to FOLFIRI plus Bev. Iri is usually administered as a short-term 90-min. infusion. However, the cytocidal activity is S-phase specific, and carboxylesterases, that convert Iri into SN-38, are less likely to become saturated when Iri is given as a long-term infusion. Therefore, a low dose of Iri given as a long-term infusion is expected to enhance antitumor activity. We conducted a randomized phase II study to compare this regimen with FOLFIRI plus Bev. Methods: The subjects comprised 120 chemotherapy-naïve patients with MCRC. The study group received 24-hr infusion of Iri at a dose of 125 mg/m2 on days 1 and 15, combined with oral S-1 80 mg/m2 on days 1 to 14. The FOLFIRI group received Iri at a dose of 150 mg/m2, 5-FU given at a dose of 400 mg/m2 as a bolus injection and at a dose of 2400 mg/m2 as a 46 hr-infusion, 200 mg/m2 of leucovorin on days 1 and 15. Bev was given at a dose of 5.0 mg/kg on days 1 and 15 in both groups. Treatment was repeated every 4 weeks. The primary endpoint was the 1 y progression-free survival (PFS). Secondary endpoints were PFS, response rates (RR), overall survival (OS), and adverse events (AEs). Results: From October 2013 through December 2017, a total of 61 patients assigned to receive IRIS plus Bev (the A group) and 59 patients assigned to receive FOLFIRI plus Bev (the B group) were included in the analysis. The 1y RFS was 37.3% in the A group and 17.0% in the B group (p = 0.0281). The PFS was 10.2 mon in the A group and 10.0 mon in the B group, and the median OS was 27.0 mon and 28.6 mon, respectively (p = 0.26, p = 0.68). RR was significantly higher in the A group (87.0%) than in the B group (61.7%) (p = 0.005). The main grade 3 or 4 AEs were neutropenia (27.8%) and diarrhea (11.1%) in the A group and neutropenia (23.4%) and leukopenia (6.4%) in the B group. Conclusions: Our results showed that Iri, given biweekly as a 24-hour infusion in combination with oral S-1 and Bev, is a highly effective and well-tolerated regimen for the first-line treatment of MCRC. Clinical trial information: UMIN000014664.
The combination of TAS-102 and bevacizumab as the third-line chemotherapy for metastatic colorectal cancer (TAS-CC3 Study).
Authors: Kosugi Chihiro , Kamiyama Hirohiko , Yoshida Yoichiro , Yoshida Hiroshi , Ishibashi Keiichiro , Ihara Keisuke , Takahashi Makoto , Kuramochi Hidekazu , Sonoda Hiromichi , Yoshimatsu Kazuhiko , Fukazawa Atsuko , Matsuda Akihisa , Yamaguchi Satoru , Ishida Hideyuki , Hasegawa Suguru , Yamada Takeshi , Narushima Kazuo , Shuto Kiyohiko , Sakamoto Kazuhiro , Koda Keiji
Published: January 2019

614

Background: TAS-102 improved overall survival of metastatic colorectal cancer (mCRC) patients with median progression free survival (PFS) of 2.0 months (RECOURSE trial). Subsequently, the combination of TAS-102 and bevacizumab has been shown to extend median PFS with 3.7 months (C-TASK FORCE). However, this study included patients with 2nd line and 3rd line chemotherapy. Our study was planned exclusively for patients receiving this combination as a 3rd line chemotherapy to investigate clinical impact of this combination beyond cytotoxic doublet. Methods: This phase II study was conducted in investigator-initiated, open-label, single-arm, multicentered manner in Japan. Eligible patients were 20-80 years old, and had to have an ECOG performance status of 0 or 1; had confirmed unresectable mCRC with histologically diagnosed adenocarcinoma; were refractory or intolerant to fluoropyrimidine, irinotecan, and oxaliplatin in the 1st and the 2nd line chemotherapy. TAS-102 (35 mg/ m²) was given orally twice daily on days 1–5 and 8–12 in a 4-weeks cycle, and bevacizumab (5 mg/ kg) was administered by intravenous infusion for 30 minutes in every 2 weeks. The primary endpoint was progression free survival (PFS), and the secondary endpoints were time to treatment failure (TTF), response rate (RR), overall survival (OS), and safety. Results: Between June 2016 and August 2017, 32 pts were enrolled. The median PFS was 4.5 months, and the median OS was 9.3 months. Partial response was observed in 2 patients. The most common adverse events above grade 3 were neutropenia (15 patients) followed by thrombocytopenia (4 patients). Treatment-related serious adverse events were reported in 1 patient. There were no non-hematologic adverse events above grade 3. No treatment-related deaths occurred. Conclusions: This is the first study which involves the combination TAS-102 and bevacizumab as the 3rd line chemotherapy in the setting beyond cytotoxic doublet for the patients with mCRC. This study met its primary endpoint PFS, which is comparable to the results of C-TASK FORCE study. This combination has a potential to be one of therapeutic options of the 3rd line chemotherapy for mCRC. Clinical trial information: 000022438.
Timing of first surveillance colonoscopy in stage I colon cancer patients and the association with colon cancer-specific survival.
Authors: Hines Robert Brooks , Jiban Md Jibanul Haque , Specogna Adrian V. , Vishnubhotla Priya , Lee Eunkyung , Troy Steven , Zhang Shunpu
Published: January 2019

618

Background: Surveillance colonoscopy following curative surgery in stage I colon cancer patients is controversial. This study was conducted to assess the relationship between timing of first surveillance colonoscopy and 5-year colon cancer-specific survival. Methods: This was a retrospective cohort study of the Surveillance, Epidemiology, and End Results database combined with Medicare claims. Stage I colon cancer patients (66-84 years of age) were categorized according to receipt of first colonoscopy following cancer-directed surgery as: Year 1, Year 2, Year 3, and No Colonoscopy within 3 years of surgery. Propensity score weighting was used to balance covariates. Cox regression was used to obtain hazard ratios for the relative risk of 5-year colon cancer-specific death, adjusted survival estimates, and the number needed to treat (NNT) with colonoscopy in Year 1 to prevent a colon cancer-specific death in the other groups. Results: There were 8,494 stage I colon cancer patients available for analysis. Regarding 5-year colon cancer-specific mortality, compared to Year 1 patients, the No Colonoscopy group experienced 2.2 times the risk of colon cancer-specific death (HR, 2.23; 95% CI, 1.38 to 3.61). Those who received ≥ 1 additional colonoscopies in the two years following their initial assessment experienced a significant 73% decreased risk of death (HR, 0.27; 95% CI, 0.16 to 0.45). Delaying colonoscopy (Years 2 & 3) did not result in a statistically significant increased risk of death. Although the absolute difference in 5-year adjusted survival was small, if all patients in the No Colonoscopy group received a colonoscopy in Year 1, 46.2% (n = 49.9) of the 108 colon cancer deaths that occurred in this group could have been prevented. Conclusions: Although stage I colon cancer patients have a good prognosis, patients who received colonoscopy within one year of cancer-directed surgery experienced significantly better survival than patients who did not receive colonoscopy within 3 years of surgery. The results of this study justify efforts to ensure that stage I colon cancer patients receive colonoscopic surveillance testing approximately 1 year following cancer-directed surgery.
Trends in radiation dose and technique for anal canal squamous cell carcinoma.
Authors: Abel Stephen , White Richard , Hasan Shaakir , Finley Gene Grant , Monga Dulabh K. , Raj Moses S. , Kirichenko Alexander V. , McCormick James , Wegner Rodney E
Published: January 2019

621

Background: Anal canal squamous cell carcinoma (SCC) is managed definitively with chemo and XRT, reserving surgery for salvage. Many different radiation dose schemes have been used, varying from 30 Gy to doses exceeding 60 Gy. RTOG 0529 established IMRT as a standard of care for anal canal SCC, using doses of 50.4-54 Gy. We used the National Cancer Database(NCDB) to examine trends in dose selection and radiation technique over time, as well as any potential effect on outcome. Methods: We queried the NCDB from 2004-2015 for cases of anal canal SCC stage 1-3, treated with definitive doses of XRT to the pelvis with chemo. Dose escalation was defined as > 54 Gy. Univariable and multivariable analyses were performed to identify factors predictive of increased dose and overall survival (OS). Propensity-adjusted Cox proportional hazard ratios for survival were used to account for indication bias. Results: We identified 7,792 patients meeting the eligibility criteria, with 4,269 treated to conventional doses and 3,163 treated to > 54 Gy. Patients that were older, had government or private insurance, were treated with IMRT, or at an academic center in a more recent year were less likely to get dose escalation. Increasing T and N stage were predictive of escalated dose. The use of dose escalation decreased over time, from 50% in 2005 to 30% in 2015. In contrast, IMRT use increased over that time from 2% to 63%. On multivariable analysis increasing age, higher comorbidity score, treatment at an academic center, and increasing stage corresponded to worse OS. Increased income, private insurance, IMRT use, increased distance to facility, and female gender all predicted improved OS. Multivariable analysis with propensity score included confirmed increased age, higher comorbidity score, income, distance, and gender as predictive of OS. In addition, escalated dose was found to have inferior outcome (OR: 1.10 95%CI: 1.01-1.20, p = 0.03). Conclusions: The results of this NCDB analysis show a steady increase in the use of IMRT over time, with a corresponding decrease in dose escalation. In this study, dose escalation was shown to have inferior outcomes, although that result is likely influenced by the increasing age, stage, and comorbidity scores in that group of patients.
Squamous cell carcinoma of the rectum: Practice trends and patient survival.
Authors: Dutta Sunil W , Alonso Clayton E , Waddle Mark Raymond , Khandelwal Shiv R. , Janowski Einsley-Marie , Trifiletti Daniel Michael
Published: January 2019

625

Background: Leverage the National Cancer Database (NCDB) to evaluate trends in management of squamous cell cancer (SCC) of the rectum and their effect on survival for this uncommon tumor. Methods: Data was obtained from the NCDB for patients diagnosed with SCC of the rectum between 2004 and 2014, including cT1-4, cN0-2, cM0 (cohort A, n = 2,296) tumors. A subgroup analysis was performed on locally advanced tumors (cT1-T2, N+ or cT3, N any, subcohort B, n = 883), treated with chemoradiation (n = 706) or trimodality therapy (n = 177) including chemotherapy, radiation, and surgery. Pathological complete response rate following neoadjuvant therapy was obtained. Univariate and multivariate logistic regression analyses were performed to generate hazard ratios (HR) investigating factors associated with overall survival. Kaplan-Meier (K-M) method was used to estimate overall surviving proportion at 5 and 10 years. Results: The median age was 60 years with a strong female predilection (71% female). Among patients treated with neoadjuvant therapy, 36% achieved a complete pathological response at a median interval of 67 days from completion of radiation therapy to surgery. The K-M estimated 5 and 10 year overall survival for stage I disease was 71.3% and 57.8%, respectively; stage II disease was 57.0% and 38.9%, respectively; stage III disease was 57.8% and 41.5%, respectively. On multivariate analysis, increased age, male gender, more co-morbidities, and higher cT category ( P < 0.001 for each) resulted in worse survival. For locally advanced tumors (subcohort B), there was no difference in survival between chemoradiation alone compared to trimodality therapy ( P = 0.909 on multivariate analysis). Conclusions: Most providers manage locally advanced SCC of the rectum similar to anal cancer, which results in equivalent overall survival and spares patients from the additional morbidity associated with surgical resection. [Table: see text]
Benefit of adjuvant chemotherapy in patients with high-risk UICC II colon cancer T4N0M0: A ten-year population-based analysis of 3544 cases.
Authors: Teufel Andreas , Fürst Alois , Gerken Michael , Hohenthanner Ina , Klinkhammer-Schalke Monika
Published: January 2019

628

Background: The benefit of adjuvant chemotherapy in UICC stage III colon carcinoma has been demonstrated in numerous studies. For UICC stage II such an advantage was not shown. However, it remains controversial whether adjuvant chemotherapy might be considered in certain high-risk UICC stage II situations. High-risk factors include T4 tumors, associated with an increased risk of recurrence and poorer prognosis due to their more aggressive biological behavior. Methods: The present population-based, multicenter cohort study investigated the influence of adjuvant chemotherapy on survival and recurrence rates in UICC stage II in the high-risk situation T4N0M0. It is based on an anonymized nationwide ADT dataset and includes 208,030 patients diagnosed with colorectal cancer from 2002 to 2011. A total of 3544 patients with a T4 tumor were identified, of whom 34.3% (1215 patients) received adjuvant chemotherapy and 65.7% (2329 patients) none. Results: Median overall survival was markedly prolonged in subjects who received adjuvant chemotherapy from 4.5 years (SD 0.163, 95% CI 4.1-4.8) to 8.1 years (SD 0.474, 95% CI 7.2 -9.0; p < .001). After 5 years, 69.5% of chemotherapy patients were still alive compared to 45.1% of non-chemotherapy patients. After adjusting for factors in a multivariable Cox regression analysis, the significant benefit of adjuvant chemotherapy for overall survival was maintained (HR = 0.642, 95% CI 0.555-0.743, p < .001). The relative cumulative risk of recurrence in the multivariable analysis was HR = 0.696 (95% CI 0.580-0.843, p < .001) for chemotherapy patients. Furthermore, a highly significant improvement in relapse-free survival through chemotherapy was demonstrated (HR = 0.634, 95% CI 0.555-0.725, p < .001). Conclusions: In this representative study, a significant advantage of adjuvant chemotherapy for UICC stage II colon carcinoma patients with a T4 tumor was demonstrated in terms of overall survival, recurrence rate and relapse-free survival. On the basis of these results, adjuvant chemotherapy is recommended for the high-risk situation T4.
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.
The association of age with acute toxicities in NRG oncology combined modality lower GI cancer trials.
Authors: VanderWalde Noam Avraham , Moughan Jennifer , Lichtman Stuart M. , Jagsi Reshma , Ballo Matthew T. , Vanderwalde Ari M. , Mohiuddin Mohammed , Meropol Neal J. , Kachnic Lisa A. , Garofalo Michael C. , Ajani Jaffer A. , Beart Robert W. , Anne Rani , Evans Lisa Smith , Arora Amit , Meyer Joshua E. , Lee James J. , Keech John A. , Soori Gamini S. , Crane Christopher H.
Published: January 2019

649

Background: This study sought to compare adverse events (AEs) of older and younger adults with lower gastrointestinal (GI) malignancies treated on NRG studies. Methods: Data from six NRG trials (RTOG 9811/0012/0247/0529/0822 & NSABP R-04), testing combined modality therapy (radiation and chemotherapy) in patients with anal or rectal cancer, were collected to test the hypothesis that older age was associated with increase in acute ( ≤ 90 days from treatment start) AEs. AEs were defined as GI, Genitourinary (GU), hematologic, or skin. AEs and compliance with protocol-directed therapy were compared between patients aged ≥ 70 years and < 70 years. Categorical variables were compared across age groups using the chi-square test. The association of age on AEs was evaluated using a covariate-adjusted logistic regression model, with odds ratio (OR) reported. To adjust for multiple comparisons, a p-value < 0.01 was considered statistically significant. Results: Data from 2525 patients were collected (43% female, 72% rectal cancer). There were 380 patients ≥ 70 years old (15%). Older patients were more likely to have worse baseline performance status (PS 1 or 2) (23% vs. 16%, p <0.01), but otherwise baseline characteristics were similar. Older patients were less likely to have completed their chemotherapy (78% vs. 87%, p < 0.01), but had similar median RT duration. On univariate analysis, patients ≥ 70 were more likely to experience grade ≥ 3 GI AEs (36% vs. 23%, OR 1.82, p < 0.001), and less likely to experience ≥ 3 skin AEs (8% vs. 14%, OR 0.56, p = 0.002). There was no difference between GU or hematologic AEs. On multivariable analysis, age ≥ 70 was associated with grade ≥ 3 GI AE (OR 1.80, 95% CI: 1.40, 2.31; p < 0.001) after adjusting for gender, PS, T stage, disease site, RT duration, and chemotherapy completion. Conclusions: Older patients with curable lower GI cancers who underwent combined-modality therapy were less likely to complete chemotherapy and were more likely to experience serious GI toxicity, whereas younger patients had higher rates of serious skin AEs.
Potentially avoidable acute care use among patients receiving oxaliplatin.
Authors: Roeland Eric , LeBlanc Thomas William , Ruddy Kathryn Jean , Clark-Snow Rebecca Anne , Binder Gary , Bailey William L. , Potluri Ravi C. , Schmerold Luke M. , Papademetriou Eros , Navari Rudolph M.
Published: January 2019

651

Background: Oxaliplatin (OX), used primarily in gastrointestinal cancers, is considered moderately emetogenic while multiple guidelines classify carboplatin and cisplatin as highly emetogenic chemotherapy (HEC). The new oncology outcome measure (OP-35) from the US Centers for Medicare and Medicaid Services (CMS) deems 30-day post-chemotherapy inpatient (IP) and emergency room (ED) events “potentially avoidable” if involving nausea or emesis (NV) or any of eight other toxicities. We lack data comparing avoidable IP/ED and NV events for OX relative to platinums classified as HEC. Methods: We assessed OX, cisplatin, and carboplatin courses of therapy from 4Q 2012 to 1Q 2018 using the IBM Watson Explorys database. We identified IP/ED and OP-35 toxicities (anemia, dehydration, diarrhea, fever, NV, neutropenia, pain, pneumonia, or sepsis) by diagnosis and procedure codes, and stratified results by sex and age < 70 (median age at diagnosis for colorectal cancer). An IP/ED event could involve ≥ 1 OP-35 toxicity. We also evaluated a FOLFIRINOX subgroup (receiving irinotecan ≤ 3 days after OX). Results: In sum, we identified 4,231 OX courses (382 FOLFIRINOX) (Table). OP-35 toxicities occurred in 75% of IP/ED events; of these, 34% OX and 42% FOLFIRINOX involved NV. Rates of IP/ED, IP/ED OP-35-defined toxicity, and NV after OX were consistent with cisplatin and carboplatin. Among patients receiving OX, women age < 70 (n = 1388) had higher NV rates vs. others (p < 0.001). Conclusions: Roughly one-third of patients receiving OX experienced IP/ED events ≤ 30 days post chemotherapy. Most involved ≥ 1 of 10 OP-35 toxicities, meeting CMS’ criteria as potentially avoidable acute care. OX IP/ED rates and NV rates were similar to other platinums and were worse among women age < 70, suggesting more aggressive antiemetic prophylaxis should be evaluated. [Table: see text]
The impact of psychosocial distress on survival in patients diagnosed with gastrointestinal (GI) malignancies.
Authors: Al-Hashami Zamzam Salam , Ho Cheryl , Moore Sara , Leung Bonnie , Lim Howard John , Bates Alan
Published: January 2019

654

Background: A cancer diagnosis can cause psychological distress that adversely affects patients’ emotional, social, spiritual and physical capabilities. The aim of this study is to identify factors associated with increased risk for psychosocial distress and to evaluate the influence of anxiety and depression on survival of GI cancer patients. Methods: All patients with GI cancer referred to BC Cancer from 2011-2015 who completed a prospective Psychosocial Screen for Cancer – Revised within 6 months of cancer diagnosis were included in the study. Baseline characteristics were collected from the BC Cancer registry. Patient groups were compared using the Chi-squared Fisher’s exact test. OS was calculated using the Kaplan Meier method, compared using the log rank test and Cox proportional hazards model. Results: 8722 patients were included in the analysis. Baseline characteristic: median age 67, male 60% , metastatic disease 29%. Colorectal/anal cancers (60%) were the most common followed by pancreatic cancer (11%). Patients with anxiety and depression were more likely to be younger (aged 64 and less), female and have metastatic disease. Patients with anxiety were more likely to get chemotherapy. Depression was associated with less chemotherapy use. Anxiety and depression were associated with increased psychosocial needs including emotional, informational, physical, spiritual, social/family concerns (p < 0.001). Psychological distress was not influenced by the patient’s geographic location or socioeconomic status. Median OS for patients with anxiety was 20 m vs no symptoms 27 m (p < 0.001) and depression 17 m vs no symptoms 27m (p < 0.001). The impact on OS remained significant for anxiety and depression in a multivariate model that included age, sex, metastatic status and chemotherapy use. Conclusions: Patients with GI malignancies who are female, younger than 64 and have metastatic disease are at risk for psychological distress. Anxiety and depression were associated with poorer survival outcomes even when controlling for age, sex, metastatic status and chemotherapy. Mobilizing resources to meet patients’ needs is important and should be implemented as part of patients’ comprehensive care.