Curative Chemoradiotherapy Research Articles

1112P - Nutritional support dependence after curative chemoradiotherapy in head and neck cancer: A supplementary analysis of a phase II trial (JCOG0706S1)

Background: Curative chemoradiotherapy (CRT) for locally advanced head and neck cancer (LA-HNC) causes severe acute and late adverse reactions, including nutritional support dependence. The aim of this supplementary analysis of a previous single-arm phase II study of CRT with S-1 plus cisplatin for unresectable LA-HNC (JCOG0706) which demonstrated promising efficacy (Cancer Sci.2015;106:726) was to explore risk factors of laryngo-esophageal dysfunction-free survival (LEDFS) and nutritional support dependence over 12 months (NSD12M). Methods: The study population comprised 45 patients (pts) in the JCOG0706. Risk factors of LEDFS and NSD12M were analyzed using Cox regression models and logistic regression models, respectively, with consideration to the pts’ laboratory data just before CRT. Radiation fields were reviewed to analyze the relationship between the extent of irradiated fields and functional outcomes. Results: Proportions of alive without nutritional support at registration and 2, 6, 12, and 24 months after registration were 82.2%, 35.6%, 68.9%, 77.8%, and 64.4%. All six pts who required nutritional support at 12 months remained tube feeding-dependent thereafter. With a median follow-up period of 3.5 years of all pts, 3-year LEDFS was 48.9%. For LEDFS, the hazard ratio was 0.42 in pts with nutritional support at registration (vs. without nutritional support; 95% confidence interval [CI] 0.17-1.04). For NSD12M, odds ratio was 6.78 in pts with hemoglobin less than the median value of 13.4 g/dL (vs. higher than or equal to the median; 95% CI 1.24-36.85); and was 6.00 in pts with albumin less than the median value of 3.9 g/dL (vs. higher than or equal to the median; 95% CI 1.11-32.54). Primary sites in disease-free pts with NSD12M were the oropharynx (N = 2) or hypopharynx (N = 1), and all their pharyngeal constriction muscles were irradiated with a curative dose of 70 Gy/35 fr. Conclusions: Functional outcomes were affected by severe dysphasia requiring nutritional support before CRT, and lower pretreatment values of hemoglobin and albumin. These risk factors should therefore be taken into consideration in planning treatment strategy for pts with LA-HNC. Clinical trial identification: UMIN000001272. Legal entity responsible for the study: JCOG. Funding: National Cancer Center Research and Development Fund (23-A-16, 23-A-21, 25-B-2 and 26-A-4); Grants-in-Aid for Cancer Research (18-19, 20S-3,20S-6) from Ministry of Health, Labour and Welfare of Japan. Disclosure: All authors have declared no conflicts of interest.

A Limited Time to Act: Cervical Cancer Stage Progression Prior to Treatment

Background: Cervical cancer is the leading cause of cancer death for women in sub-Saharan Africa where access to timely diagnosis and treatment remains a major challenge. Several investigators have documented the adverse impact of delays during curative chemoradiation on survival: 2%-5% decreased survival per week delay. However, the clinical impact of delays in initiating treatment has not previously been estimated and is key to direct allocation of resources and patient care. Aim: To estimate the duration treatment initiation delay leading to a one-stage progression in cervical cancer. Methods: Radiation is available in Botswana from a single linear accelerator and services are provided free of cost to Botswana citizens. Two prolonged service interruptions (late 2014 due to mechanical failure/upgrades, and late 2015 for machine replacement) contributed to substantial additional delays in accessing treatment of several months after service resumed. Using these natural experiments and the prospectively enrolling Thabatse Cancer Cohort (included cases enrolled from September 2014 to January 2018), we used instrumental variable methods to estimate the mean number of weeks to progress one stage (e.g., IIIA to IVA). Our instrument was a binary variable indicating treatment initiation occurred during service interruption. We used inverse probability weighting to adjust for possible bias in exposure to the instrument by HIV status, age, and income. Cancer stage was considered ordinal and we used Poisson regression to calculate weeks for stage progression. We calculated confidence limits using bootstrapping from 500 samples. Analyses were performed in SAS 9.4. Results: A total of 301 cervical cancer cases were included with 138 (46%) exposed to service disruption and 163 (54%) not exposed. The majority, 217 (72%), were HIV-infected with 86% on ART prior to cancer diagnosis. At time of treatment, 27 (9%) stage I, 108 (36%) stage II, 113 (38%) stage III, and 53 (18%) stage IV. Median time from diagnosis to initiation of treatment of all patients was 9.7 weeks (IQR 6.3-13.7), and was longer in those exposed to service disruption (11.0 weeks [IQR 7.7-15.1]) than those not exposed (8.0 weeks [IQR 5.3-11.7]. Time for progression of one cancer stage was 8.9 weeks (95% CI 4.6-15.8). Among HIV-infected women, estimated time for one-stage progression was 6.5 weeks (95% CI 2.3-12.3), significantly faster than HIV-uninfected women ( P < 0.001). The small number of HIV-uninfected women prevented separate estimation. Conclusion: Stage progression is rapid in locally advanced cervical cancer with typical treatment delays of two months associated with a full stage increase. These estimates may not generalize to contexts with lower HIV prevalence; however add urgency to effort to improve efficient access to treatment and avoidance of waiting lists.

P1.12-10 Patterns of Curative Chemo-Radiotherapy Regimen and Impacts on the Outcome of Limited Stage SCLC in a Canadian Institution: 2010 – 2015 Diagnoses

Curative intent chemotherapy and radiotherapy (ChemoRT) is the widely recommended treatment for limited stage (LS) small cell lung cancer (SCLC) follow by prophylactic cranial irradiation (PCI) in those who responded to the initial therapy. LS-SCLC is however characterized by high relapse rate with only about 20% surviving to 2 years. Our objective is to examine the characteristics, treatment patterns and overall survival of LS-SCLC for patients diagnosed within a 5-year period at the Tom Baker Cancer Centre, Canada, prior to wide adoption of emerging treatment options including surgery and immunotherapy in the curative and palliative settings respectively. Using the Glans-Look Lung Research (GLR) database, we defined the clinical and demographic features of patients diagnosed with LS-SCLC from 2010 to 2015, determined the rate of systemic treatment uptake, and investigated the impact of PCI, curative intent, and palliative treatments on overall survival. We summarized our findings with descriptive statistics (including Fisher’s Exact test) and Kaplan Meier survival curves using SPSS. Statistical significance was set at p value < 0.05 and 95% confidence intervals. About a third (107/349, 31%) of patients diagnosed with SCLC from 2010 to 2015 were LS-SCLC, with median age of 67 years. Over the 5-year period, systemic treatments uptake rates and patterns fluctuates. Overall, > 50% received ChemoRT and 65% of the ChemoRT group also received PCI. Curative concurrent RT dose 45 – 55Gy, 25 fractions schedule was more common (55%). Few stage T1a-2a, N0-1 LS-SCLC had surgery (5%). Thirty eight percent of those who received initial curative intent treatments further received some palliative treatments for disease recurrence or progression {8% (2/26) initial Surgery ± Adjuvant and 92% (24/26) ChemoRT}. The median overall survival for the cohort was 24 months (p < 0.001). There were more than 50% survival at 60 months for patients treated with curative 15 fractions concurrent ChemoRT (p < 0.001). Most patients received ChemoRT while a few had surgery. Concurrent 15 fractions ChemoRT may offer better survival benefits than the 25 fraction schedule. The impact of PCI on LS-SCLC and other survival outcomes will be presented.

The promise of image-guided brachytherapy of better clinical outcomes in treatment of cervical cancer: Does it deliver? An Indian scenario

PurposeThe purpose of this series is to study the effectiveness of MRI based image-guided brachytherapy (IGBT) in Indian patients with cervical cancer who mostly present in later stages with bulky diseases. Patients and methods151 cervical cancer patients treated at our institution in last four years, with definitive chemoradiation followed by MRI-based brachytherapy were reviewed. With median follow up of 26 months, Kaplan Meier estimates at two years were calculated for local control (LC), pelvic control (PC), disease-free survival (DFS) and overall survival (OS). Also, severe late sequelae were reported. ResultsThe patients predominantly presented with locally advanced cervical cancer in FIGO stages IIB (53.6%) and IIIB (23.2%). Tumour dimensions at diagnosis were ≥5 cm in 56.3% and pelvic nodal involvement was found in 38.4% of the patients. 94% of the patients received curative chemoradiation. Mean HRCTV volume at the time of brachytherapy was 42.2 ± 19 cm3 and mean cumulative dose to HRCTV was 78.9 ± 5.6 Gy. Overall LC, PC, DFS and OS at 2 years were 88.7%, 88.1%, 82.2% and 94% respectively. The predictors for local failure were FIGO stage (p = 0.002) and tumour size at diagnosis (p = 0.009). Late grade 3–4 bladder and bowel toxicities were observed in 3.8% of the patients. ConclusionOur review demonstrates that IGBT is an effective strategy to improve locoregional control with limited long-term sequelae in patients with locally advanced extensive cervical cancer in the setting of a developing country.

Safety and Feasibility of a Pragmatic Pre-planned, Hypofractionated High Dose Rate Brachytherapy Approach to Carcinoma of the Cervix in Low and Middle Income Countries

The burden of cervical cancer is high in low and middle income countries (LMIC) where access to curative radiation treatment is limited. A nonprofit organization donated a high dose rate (HDR) brachytherapy afterloading unit to the sole cancer center in Senegal in 2013. We describe the initial experience of a novel treatment approach using pre-planned brachytherapy as a component of curative chemoradiation in Senegal.

Radiotherapy-induced anti-tumor immune response and immune-related adverse events in a case of recurrent nasopharyngeal carcinoma undergoing anti-PD-1 immunotherapy

BackgroundTreatment of recurrent nasopharyngeal carcinoma is a challenging clinical problem. We report the case of a 46 year old male showing excellent response and signs of immunostimulation following re-re-irradiation for recurrent nasopharyngeal carcinoma under systemic treatment with pembrolizumab.Case presentationPatient was first diagnosed with locoregionally advanced, non-keratinizing nasopharyngeal carcinoma in 2010. After achieving complete remission following induction chemotherapy and concurrent curative chemoradiation, the patient subsequently developed distant and locoregionally recurrent disease. He received various treatments (neck dissection, radiotherapy to a bony metastasis, palliative chemotherapy, stereotactic re-irradiation of local recurrence) before initiation of anti- PD-1 immunotherapy with pembrolizumab in January of 2016. Following marked local progression 6 months thereafter, we performed re-re-irradiation of the recurrent tumor after careful evaluation and treatment planning. While treatment was well tolerated, the patient subsequently developed marked clinical and radiological signs of immunostimulation with mucosal irritation and swelling of lacrimal and salivary glands as described in the report. Immunotherapy with pembrolizumab was reinitiated, with re- staging showing excellent response with regression of all tumorous lesions. At the time of this report, following near complete recovery of inflammatory symptoms, the patient remains in excellent condition and free from recurrence under treatment with pembrolizumab.ConclusionsTo our knowledge, we report the first observation of a combined effect of immunotherapy and radiotherapy in a patient with recurrent nasopharyngeal carcinoma. Demonstrating distinct signs of immunostimulation as well as excellent tumor response in a heavily pretreated patient progressing under anti-PD-1 immunotherapy, the case adds to the rising paradigm of an immunostimulatory effect of radiotherapy in patients undergoing treatment with immune checkpoint inhibitors.

Impact of Human Immunodeficiency Virus Infection on Survival and Acute Toxicities From Chemoradiation Therapy for Cervical Cancer Patients in a Limited-Resource Setting

To prospectively compare survival between human immunodeficiency virus (HIV)-infected versus HIV-uninfected cervical cancer patients who initiated curative chemoradiation therapy (CRT) in a limited-resource setting. Women with locally advanced cervical cancer with or without HIV infection initiating radical CRT in Botswana were enrolled in a prospective, observational, cohort study from July 2013 through January2015. Of 182 women treated for cervical cancer during the study period, 143 women initiating curative CRT were included in the study. Eighty-five percent of the participants (122 of 143) had stage II/III cervical cancer, and 67% (96 of 143) were HIV-infected. All HIV-infected patients were receiving antiretroviral therapy (ART) at the time of curative cervical cancer treatment initiation. We found no difference in toxicities between HIV-infected and HIV-uninfected women. The 2-year overall survival (OS) rates were 65% for HIV-infected women (95% confidence interval [CI] 54%-74%) and 66% for HIV-uninfected women (95% CI 49%-79%) (P=.70). Factors associated with better 2-year OS on multivariate analyses included baseline hemoglobin >10g/dL (hazard ratio [HR] 0.37, 95% CI 0.19-0.72, P=.003), total radiation dose≥75Gy (HR 0.52, 95% CI 0.27-0.97, P=.04), and age<40years versus 40-59years (HR 2.17, 95% CI 1.05-4.47, P=.03). Human immunodeficiency virus status had no effect on 2-year OS or on acute toxicities in women with well-managed HIV infection who initiated curative CRT in Botswana. In our cohort, we found that baseline hemoglobin levels, total radiation dose, and age were associated with survival, regardless of HIV status.

Prognostic significance of nutritional risk index in patients with metastatic esophageal squamous cell cancer.

156 Background: It has been suggested that nutritional indicators predict the prognosis of esophageal cancer. Nutritional risk (NR) as prognostic factor evaluated by NR index (NRI) in metastatic esophageal squamous cell cancer (ESCC) has not been clarified. Methods: We retrospectively reviewed the data of consecutive patients (pts) with metastatic ESCC who received chemotherapy (CTx) as initial treatment at Shizuoka Cancer Center between April 2008 and December 2015. The selection criteria were as follows: histologically confirmed squamous cell carcinoma; no indication for curative resection or definitive chemoradiotherapy (dCRT); adequate organ function; no prior CTx, radiotherapy (RT) or chemoradiotherapy; no other advanced malignancies. NR was calculated by following formula: NRI = (1.489*serum albumin) + (41.7*present body weight [BW] / ideal BW). NR was classified into 4 groups according to NRI: major (NRI &lt; 83.5), moderate (NRI = 83.5-97.5), mild (NRI = 97.5-100), none (NRI &gt; 100). Multivariate analysis was carried out using cox proportional hazard to estimate the hazard ratio for overall survival (OS). Results: The patients’ characteristics of 138 pts who met the selection criteria were as follows: median age (range), 67 (33-86) years; male/female, 123/15; performance status (PS) 0/1/2, 62/68/8; number of metastatic sites 1/2/3/4, 55/56/23/4; smoking history -/+, 19/119; previous esophagectomy -/+, 118/20; median skeletal muscle index (range), 44.5 (27.8-63.2); median body mass index (range), 20.3 (14.3-27.4); NR major/moderate/mild/none 22/37/26/53; median serum C-reactive protein (CRP) level (range), 0.75 (0.01-20.48) mg/dL. The most common chemotherapy regimen used was fluoropyrimidine plus cisplatin (93%), and 70 patients (50%) received concomitant RT. Median OS was 4.6 months in pts with major NR and 11.8 months in others (p &lt; 0.001). Multivariate analysis for OS identified PS 2, female sex, metastatic sites &gt; 2, CRP ≥ 1mg/dL, and major NR independently associated with poor survival. Conclusions: Major NR calculated by NRI formula associated with poor survival in pts with metastatic ESCC.

The association between MRI texture analysis and chemoradiotherapy outcomes in glioblastoma cases

Aim: Texture analysis can provide additional information regarding tumor heterogeneity and treatment response. The aim of this study was to evaluate whether MRI texture analysis can predict radiotherapy response and survival in glioblastoma patients.Material and Methods: A total of 26 patients with pathologically confirmed glioblastoma who had received curative chemoradiotherapy (60 Gy radiotherapy + temozolomide) underwent contrast-enhanced cranial MRI texture analysis before and after chemoradiotherapy. The region of interest was determined as the active tumor area in post-contrast axial T1 sections. The gray level intensity, standard deviation of histogram, entropy, uniformity, skewness, and kurtosis values were determined by texture analysis.Results: Comparison of the pre- and post-radiotherapy values showed an increase in entropy (6.97±0.37 vs. 7.20±0.30, p = 0.014) and a decrease in uniformity (0.21±0.12 vs.0.16±0.08, p = 0.049). Therefore, radiation therapy was determined to have caused increased heterogeneity in the active tumor region of glioblastoma. The median follow-up was 7.5 [95% confidence interval (1.8-21.63)] months, while the median overall survival was 12.5 [95% confidence interval (4.24-20.81)] months. Young age, high performance statusand low entropy value after radiotherapywere associated with longer survival according to the Kaplan-Meier analysis (p = 0.014, p = 0.031, p = 0.034, respectively).Conclusion: Based on these results,entropy measurements can be recommended for use as a new prognostic factor for glioblastoma.Keywords: Glioblastoma; Entropy; Radiotherapy; Survival; Texture Analysis.

Experience with curative radiotherapy for cervix cancer in the Bahamas for 2006-2016.

Cervix cancer is a significant health problem. As access to quality care in Small Island Developing States improves, and cancer centers become established, providers of care can summarize local experience to benchmark system quality and look for ways to further improve value. This is a retrospective study of all cases of cervix cancer managed 2006-2016 at The Cancer Centre Bahamas, in conjunction with Princess Margaret Hospital, Nassau, affiliated with The University of West Indies. Seventy-two women received curative radiotherapy or chemoradiotherapy. Herein are reported presenting characteristics, treatments, waiting and overall treatment times, plus outcomes of recurrence, survival, and adverse events. For 68 newly diagnosed cases, median waiting time (diagnosis to commencing treatment) was 110days. It was 90days for those 47 cases who had no prior surgery or neoadjuvant chemotherapy. Overall, 99% of intended external radiotherapy fractions, 74% of brachytherapy sessions, and 79% of concurrent weekly chemotherapy were administered. For all 72 cases, median overall treatment time was 63days; and for the 47 case sub-group, it was 78days during 2006-2010 and 65days during 2011-2016 (p = 0.005), so improving over calendar time. Four cases experienced grade 3-4 toxicities. Twelve had urological complications from disease or treatment. Five cases experienced local failure; eight experienced distant failure. Newly diagnosed stage 2B (26/72) had a 2-year survival of 71%. This report demonstrates the impact of providing curative radiation-based treatments for cervical cancer in a small state. It suggests ways to further improve operations and justifies additional research.

Application of the new 8th TNM staging system for non-small cell lung cancer: treated with curative concurrent chemoradiotherapy

BackgroundThe eighth tumor, node, metastasis (TNM) staging system (8-TNM) for non-small cell lung cancer (NSCLC) was newly released in 2015. This system had limitation because most patients included in the analysis were treated with surgery. Therefore, it might be difficult to reflect prognosis of patients treated with curative concurrent chemoradiotherapy (CCRT). Purpose of this study was to investigate clinical impact of the newly published 8-TNM compared to the current seventh TNM staging system (7-TNM) for locally advanced NSCLC patients treated with CCRT.MethodsNew 8-TNM was applied to 64 patients with locally advanced NSCLC who were treated with CCRT from 2010 to 2015. Changes in T category and stage group by 8-TNM were recorded and patterns of change were evaluated. Survival was analyzed according to T category, N category, and stage group in each staging system, respectively.ResultsAmong the total of 64 patients, 38 (59.4%) patients showed change in T category while 22 (34.4%) patients showed change in stage group using 8-TNM compared to 7-TNM. Survival curves were significantly separated in the 8-TNM stage group (p = 0.001) than those in the 7-TNM (p > 0.05). Especially, survival of newly introduced stage IIIC by 8-TNM was significantly lower than that of others. On the other hand, there was no significant survival difference between T categories in each staging system.ConclusionsSubdivision of stage III into IIIA, IIIB, and IIIC by 8-TNM for patients treated with CCRT better reflected prognosis than 7-TNM. However, subdivision of T category according to tumor size in 8-TNM might be less significant.

Abstract 4751: Correlating the genomic and transcriptomic profiles of pre-treatment cervical tumor biopsies with patient recurrence after definitive chemoradiation

Abstract Purpose: The purpose of this study was to identify genomic mutations that correlate with patient recurrence after curative intent chemoradiation therapy in advanced stage cervical cancer patients. Methods: Pre-treatment cervical tumor biopsies and normal blood were prospectively collected from patients treated at Washington University in St. Louis. DNA and RNA was isolated from the fresh frozen tumor biopsies and sent for next-generation sequencing and RNAseq respectively. Targeted exome sequencing was done using a panel of 127 known cancer associated genes, and an additional 8 genes previously reported to be mutated in cervical cancer. Gene tiling was done to probe for 30 different HPV subtypes. Results: The mutational signatures of single nucleotide polymorphisms were an APOBEC cytidine deaminase and CpG site cytidine deamination mutagenesis pattern. The non-silent somatic mutations were analyzed by online prediction algorithms to assess the mutation’s putative effect on protein function. Univariate COX regression was used to correlate patient recurrence with non-silent putatively functional mutations. In our patient cohort 88% of samples were HPV positive, with 74% being the high-risk HPV 16 and 18 subtypes. Patient’s with HPV positive tumors had increased progression-free survival when compared to the HPV negative patient tumors; and the HPV positive patients with HPV 16 had increased progression-free survival over the other HPV subtypes. Complete gene tiling of the HPV 16 and 18 subtypes allowed us to determine whether the HPV DNA was integrated in the host genome or retained episomally. In our patient cohort less than 30% of samples had integrated HPV DNA, and there was no significant difference in progression-free survival between patients with integrated or episomal HPV. Conclusions: The genomic analysis of our advanced staged cervical cancer patient cohort found that epigenetic modifiers were frequently mutated and that cytidine deamination mutagenesis was primarily responsible for the generation of the SNP mutations. Our study identified NSD1 mutations as being correlated with tumor recurrence, indicating that histone modifications and chromatin structure may play an important role in tumor response to ionizing radiation therapy. Gene expression analysis is currently ongoing. Citation Format: Fiona J. Ruiz, Julie K. Schwarz. Correlating the genomic and transcriptomic profiles of pre-treatment cervical tumor biopsies with patient recurrence after definitive chemoradiation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4751. doi:10.1158/1538-7445.AM2017-4751

Toxicity and Outcomes in Patients With and Without Esophageal Stents in Locally Advanced Esophageal Cancer

Esophageal stenting is often considered to relieve dysphagia in patients with locoregionally advanced esophageal cancer. We sought to determine the effects of stenting on the incidence of acute toxicity and oncologic outcomes in patients undergoing chemoradiation therapy (CRT). The data from patients treated with curative intent CRT for locoregionally advanced esophageal cancer at the University of Utah were retrospectively analyzed. The χ2 or Fisher exact test was used to compare the demographic and tumor characteristics between patients with and without esophageal stenting before RT. Univariate and multivariate analyses using logistic regression modeling were used to identify the predictors of acute toxicities. A propensity score-matched analysis with shared frailty Cox hazard regression was performed according to stent status to identify the stent effect on survival. Acute toxicities were graded using the Common Terminology Criteria for Adverse Events, version4. From 2005 to 2013, 103 consecutive patients received CRT. Of the 103 patients, 28 had a stent in place during CRT. The median dose was 50.4Gy for all patients. Grade ≥3 acute toxicities were seen in 71% of the stent versus 27% of the no-stent patients (P<.01), including esophagitis (39% vs 20%; P=.05), dehydration (29% vs 13%; P=.07), and anorexia (14% vs 5%; P=.13). Of the 103 patients, 29% of the stent and 51% of the no-stent patients underwent esophagectomy (P=.05). The only significant predictor for acute toxicity on multivariate analysis was esophageal stenting (odds ratio 8.1; P<.01). After propensity score matching, the stent patients had a worse median overall survival compared with the no-stent patients (11.5 vs 22.0months; hazard ratio 2.3; P=.016). In patients undergoing CRT with curative intent, esophageal stenting was associated with significantly increased grade ≥3 acute toxicities, fewer patients proceeding to esophagectomy, and worse overall survival.

Clinical evaluation of palliative chemoradiotherapy for metastatic esophageal cancer.

Platinum-based chemotherapy is considered a standard treatment option for patients with metastatic esophageal carcinoma. However, the overall survival of patients receiving such treatment is <1 year. A common presenting symptom of esophageal cancer is dysphagia, which has a substantial impact on quality of life. We have now retrospectively evaluated the efficacy and safety of palliative chemoradiotherapy for patients with stage IV esophageal cancer, most of whom are unfit for curative chemoradiotherapy. Fifty consecutive patients diagnosed with stage IV esophageal cancer were treated with concurrent chemoradiotherapy at Kindai University Hospital between April 2008 and December 2014. Most (90%) patients received a total radiation dose of at least 50 Gy, and the median number of treatment cycles per patient was four for the combination of 5-fluorouracil and cisplatin. The response of the primary tumor and the overall response were 80% and 44%, respectively. The dysphagia score was improved after chemoradiotherapy in 36 (72%) patients and did not change between before and after treatment in 14 (28%) patients. With a median follow-up time of 9.4 months from the start of chemoradiotherapy, the median progression-free survival and overall survival were 4.7 and 12.3 months, respectively. Three patients (T4b in two, T3 in one) developed esophagobronchial fistula after completion of chemoradiotherapy (n = 2) or after disease progression (n = 1), resulting in death in each case. Our results suggest that palliative chemoradioiotherapy was safe and contributed the improvement of dysphagia in patients with stage IV esophageal cancer.

Comparison of 5-FU versus capecitabine in combination with mitomycin or cisplatin in the treatment of anal cancer.

680 Background: Capecitabine is used as an alternative fluoropyrimidine to infusional 5-FU in the non-operative management of anal cancer due to its ease of administration. However, its patterns of use and long-term outcomes in the real world are poorly described. Our objectives were to determine the frequency of capecitabine use, compare the difference in outcomes, and examine the difference in treatment-related adverse events between oral and intravenous fluoropyrimidines. Methods: All anal cancer patients who received either capecitabine or infusional 5-FU as part of their curative intent chemoradiotherapy from 2010 to 2013 at any 1 of 6 comprehensive cancer centers in British Columbia were included. Chi-square and Wilcoxon-Mann tests were used to assess for associations between treatment groups and clinical characteristics and outcomes. Results: A total of 237 patients were identified; median age was 59 (IQR 53-67) years, 71 (30%) were men, 202 (85%) had ECOG 0/1, and 12 (5%) were HIV positive. Median total radiation dose was 54 cGy (IQR 50.4-54.0) and 21 (9%) underwent a colostomy prior to chemoradiation. Baseline characteristics were balanced between the two groups with respect to age, gender, ECOG, and HIV status (all p &gt; 0.05). Overall, 155 patients (65%) received capecitabine. Comparing patients who received capecitabine vs 5-FU, overall (69% vs 74%, p = 0.388) and disease-free survival rates (68% vs 71%, p = 0.637) at 5 years from diagnosis were similar between treatment groups. There were no differences with respect to rates of subsequent colostomy (16% vs 23%, p = 0.185) and abdominoperineal resection (11% vs 12%, p = 0.777). However, patients who received capecitabine were less likely to report adverse effects (51% vs 26%, p &lt; 0.001) than those who underwent 5-FU. The capecitabine group had a lower incidence of stomatitis (6% vs 40%, p &lt; 0.001) whereas the 5-FU cohort reported less frequent hand-foot syndrome (1% vs 8%, p = 0.036). Conclusions: This population-based study demonstrates a preference for capecitabine use in place of 5-FU in the curative management of anal cancer. Survival outcomes are similar between the two treatment groups, but capecitabine may be better tolerated.

Prognostic significance of tumor-infiltrating immune cells and PD-L1 expression in oesphageal squamous cell carcinoma.

13 Background: Programmed death-1 receptor (PD-1) and its ligand (PD-L1) play an integral role in the immune response against cancer. This study investigated the prognostic significance of PD-L1 expression and tumor-infiltrating immune cells (TILs) in tumor microenvironment in Chinese patients with esophageal squamous cell carcinoma (ESCC). Methods: A total of 428 archival formalin-fixed, paraffin-embedded (FFPE) ESCC samples were collected between 2004 and 2014 from treatment naïve patients with ESCC after surgery or by diagnostic endoscopic biopsy. Expression of PD-L1 was assessed by IHC. The degree of TILs infiltration was evaluated by examining the H&amp;E-stained specimens. Associations of PD-L1 expression and TILs with clinicopathological features were evaluated by non-zero correlation test. Survival distribution was compared by Kaplan-Meier and a log-rank test. The median follow-up time was 34.4 months(0.3-147.1 m). Changes of PD-L1 expression between paired tumor samples, which were collected before and after chemotherapy (2 cycles and 4 cycles or more), were also evaluated. Results: In the entire cohort, 79.7% (341/428) of specimens were PD-L1+ (defined as having ≥ 1% of tumor cell membranes showing ≥ 1+ intensity). In the intent-to-treat group (patients received curative esophagectomy or definitive chemoradiation therapy), PD-L1 positivity was associated with a significantly poorer DFS and OS. Neither PFS nor OS in palliative chemotherapy group presented a significant difference corresponding to PD-L1 expression. Furthermore, PD-L1 expression was positively associated with TIL density. Changes in PD-L1 expression was examined in 17 paired tumor tissues collected before and after treatments. Results showed that an increase in PD-L1 expression was associated with disease progression, a decrease in PD-L1 expression was associated with satisfactory chemotherapy treatment response. Conclusions: PositivePD-L1 expression was associated with a significantly worse prognosis in ESCC. These observations suggest that PD-L1 may play a critical role in ESCC cancer progression and provide a rationale for developing PD-L1 inhibitors for treatment of a subset of ESCC patients.

367P Persistent elevation of plasma interleukin-8 or interferon-γ after curative chemoradiotherapy predict early tumor recurrence and poor survival outcomes in patients with head and neck squamous cell carcinoma

Background To evaluate the prognostic significance of plasma proinflammatory cytokines in patients with head and neck squamous cell carcinoma undergoing curative chemoradiotherapy. Methods This prospective study was approved by the IRB of our institute (201406075RINC). Head and neck squamous cell carcinoma non-metastatic patients receiving curative chemoradiotherapy were prospectively enrolled. Proinflammatory plasma cytokines concentrations [interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IFN-γ, and tumor necrosis factor-α] were evaluated at two time points (before chemoradiotherapy, and 2 weeks after completion of chemoradiotherapy). Associations of the plasma level of cytokines and clinical outcomes were evaluated. Results Thirty patients were included. The primary sites of cancer were oropharynx (33%), oral cavity (23%), hypopharynx (23%), larynx (10%), and others (10%). Most patients had stage IV disease. The median radiotherapy dose was 70 Gy in 33 fractions. With a median relative short follow-up of 15.9 months, early tumor recurrence was noted in twelve 12 patients (40%), and death was noted in 6 patients (20%). Among the 8 proinflammatory plasma cytokines, IL-8 and IFN-γ were significantly associated with survival outcomes. The mean IL-8 levels before and after treatment were 1.6 and 4.1 pg/mL, respectively. The mean IFN- γ level before and after treatment were 4.7 and 2.8 pg/mL, respectively. In univariate analysis, stage IV (p = 0.047), persistent elevation (level after treatment was greater than or equal to the level before treatment) of plasma IL-8 (p=0.024) or IFN-γ (p=0.006) were significantly associated with early tumor recurrence and poor overall survival. In multivariate analysis, patients with persistent elevation of plasma IL-8 or IFN-γ, independent of stage, had significantly worse RFS (HR3.0, p = 0.038 for persistent elevation of plasma IL-8; HR 8.8, p = 0.026 for IFN-γ). Conclusions: In patients with head and neck squamous cell carcinoma undergoing curative chemoradiotherapy, persistent elevation of plasma IL-8 or interferon-γ after treatment may predict early tumor recurrence and poor overall survival. Legal entity responsible for the study National Taiwan University Hospital Funding National Taiwan University Hospital Disclosure All authors have declared no conflicts of interest.

367P Persistent elevation of plasma interleukin-8 or interferon-γ after curative chemoradiotherapy predict early tumor recurrence and poor survival outcomes in patients with head and neck squamous cell carcinoma

367P Persistent elevation of plasma interleukin-8 or interferon-γ after curative chemoradiotherapy predict early tumor recurrence and poor survival outcomes in patients with head and neck squamous cell carcinoma

Surgical Resection After Induction Treatment Versus Curative Chemoradiation Therapy in Stage IIIA (N2) Locally Advanced Non-Small Cell Lung Cancer: Meta-Analysis of 3 Large-Scale Randomized Control Studies

Surgical Resection After Induction Treatment Versus Curative Chemoradiation Therapy in Stage IIIA (N2) Locally Advanced Non-Small Cell Lung Cancer: Meta-Analysis of 3 Large-Scale Randomized Control Studies

Oligo-recurrence predicts favorable prognosis of brain-only oligometastases in patients with non-small cell lung cancer treated with stereotactic radiosurgery or stereotactic radiotherapy: a multi-institutional study of 61 subjects.

BackgroundTo investigate the prognostic value of oligo-recurrence in patients with brain-only oligometastases of non-small cell lung cancer (NSCLC) treated with stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT).MethodsPatients treated with SRS or SRT for brain-only NSCLC oligometastases in 6 high-volume institutions in Japan between 1996 and 2008 were reviewed. Eligible patients met 1), 2), and 4) or 1), 3), and 4) of the following: 1) NSCLC with 1 to 4 brain metastases on magnetic resonance imaging (MRI) treated with SRS or SRT; 2) control of the primary lesions (thorax) at the time of SRS or SRT for brain metastases (patients meeting this criterion formed the oligo-recurrence group); 3) with SRS or SRT for brain metastases, concomitant treatment for active primary lesions (thorax) with curative surgery or curative stereotactic body radiotherapy (SBRT), or curative chemoradiotherapy (sync-oligometastases group); and 4) Karnofsky performance status (KPS) ≥70.ResultsThe median overall survival (OS) of all 61 patients was 26 months (95 % CI: 17.5–34.5 months). The 2-year and 5-year overall survival rates were 60.7 and 15.7 %, respectively. Stratified by oligostatus, the sync-oligometastases group achieved a median OS of 18 months (95 % CI: 14.8–21.1 months) and a 5-year OS of 0 %, while the oligo-recurrence group achieved a median OS of 41 months (95 % CI: 27.8–54.2 months) and a 5-year OS of 18.6 %. On multivariate analysis, oligo-recurrence was the only significant independent factor related to a favorable prognosis (hazard ratio: 0.253 (95 % CI: 0.082–0.043) (p = 0.025).ConclusionsThe presence of oligo-recurrence can predict a favorable prognosis of brain-only oligometastases in patients with NSCLC treated with SRS or SRT.