Neoadjuvant Concurrent Chemoradiotherapy Research Articles

A Prospective Randomized Comparison of Concurrent Chemoradiation with Neoadjuvant and Adjuvant Chemotherapy with Concurrent Chemoradiation Alone for Locally Advanced Carcinoma Cervix

Abstract Aims: The aim of this study was to compare concurrent chemoradiation along with neoadjuvant and adjuvant chemotherapy versus concurrent chemoradiation alone in locally advanced cervical cancer regarding treatment response and toxicities. Subjects and Methods: A randomized control study was done on 116 patients with locally advanced carcinoma cervix (Stage IIB to IIIB) registered between January 2014 and February 2015. Patients were randomly divided to receive either one cycle of cisplatin/5-fluorouracil neoadjuvant chemotherapy and two cycles of the same adjuvant chemotherapy with concurrent chemoradiation with weekly cisplatin (Arm A) or only concurrent chemoradiation (Arm B). All patients received three fractions of high-dose-rate intracavitary brachytherapy after completion of the external radiation. Results: A higher proportion of the patients of chemotherapy arm achieved complete response (94%) as compared to the nonchemotherapy arm (56%), and this was statistically significant. There was a trend toward more treatment-related acute toxicity with chemotherapy. Conclusions: These results have corroborated the view that if neoadjuvant and adjuvant chemotherapies are added to concurrent chemoradiation, it could further the effects of concurrent chemoradiation for patients with locally advanced cancer of the uterine cervix.

Abstract 525: Immune-oncologic shift in programmed death-ligand 1 expression and microsatellite instability after neoadjuvant chemoradiation therapy in locally advanced rectal cancer

Abstract Purpose: We designed this study to evaluate relations between microsatellite instability (MSI) status and programmed death-ligand 1 (PD-L1) and tumor response following neoadjuvant concurrent chemoradiation therapy (CCRT) in locally advanced rectal cancer. Materials and methods: In the prospective study, we collected 54 rectal adenocarcinoma patients who underwent neoadjuvant concurrent chemoradiation therapy between August 2016 and December 2017. With exclusion criteria, we finally included 24 patients and evaluated the PD-L1 expression using immunohistochemistry (IHC) and tested the MSI status with pre- and post- CCRT samples. Human colorectal cell lines DLD 1, HT-29 and HCT116 were obtained and cell morphology, cell viability, and PD-L1 expressions were evaluated using flow cytometry 24, 48 and 72 hours after irradiation. Using 4-fields box technique, 50.4 to 54 Gy in daily 1.8Gy fractions of radiation was delivered to pelvis including rectal mass and surgery was performed 6 to 8 weeks after completion of neoadjuvant CCRT. Tumor response was estimated by using Mandard grading system. Results: According to the tumor regression grade, patients were classified into two groups; responder (grade 0, 1 or 2; 9 patients, 37.5%) and non-responder (grade 3 or 4; 15 patients, 62.5%). Between the two groups, there was no statistically significant differences in several tumor characteristics including histologic type, lymphocytic response, tumor budding, BRAF or K-ras mutations except tumor stage; more patients with advanced T stage in non-responder (p = 0.019). MSI-high status was reported in two responders (25%), but no one with pre-CCRT MSI-high status in non-responder group (relative risk = 3.143, 95% CI = 1.705 - 5.794). High PD-L1 expression on tumor marginally significantly increased from 16.7% before CCRT to 45.0% after CCRT by IHC (P = 0.053), especially in non-responder group. PD-L1 gene expression by irradiation in three human cell lines using flow cytometry analysis was increased, mostly in radio-resistant cell line, DLD 1. Conclusion: This prospective study verified the chemoradiation-induced immune-oncologic shift toward increases in PD-L1 expression that may be associated with radio-resistance. MSI status was associated with tumor response after chemoradiotherapy for locally advanced rectal cancer. Key words: Locally advanced rectal cancer, neoadjuvant concurrent chemoradiation therapy, tumor regression, microsatellite instability, programmed death-ligand Note: This abstract was not presented at the meeting. Citation Format: SungUk Bae, Hye Won Lee, Sang Jun Byun, Woon Kyung Jeong, Seong Kyu Baek. Immune-oncologic shift in programmed death-ligand 1 expression and microsatellite instability after neoadjuvant chemoradiation therapy in locally advanced rectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 525.

Effectiveness of image-guided radiotherapy for rectal cancer patients treated with neoadjuvant concurrent chemoradiotherapy: A population-based propensity score-matched analysis.

The effects of image-guided radiotherapy (IGRT, an advanced RT technology) have been debated in the literature. We compared the outcomes of locally advanced rectal cancer (LARC) patients treated with neoadjuvant concurrent chemoradiotherapy (NCCRT; with vs without IGRT) in a large population-based propensity score (PS)-matched analysis. We identified LARC patients diagnosed between 2007 and 2015 via the Taiwan cancer registry (TCR) and constructed a PS-matched cohort to balance observable potential confounders. Outcomes (R0 resection, overall survival, incidence of local regional recurrence [ILRR], rectal cancer mortality [IRCM], other cancer mortality [IOCM] and cardiovascular mortality [ICVM]) were obtained from TCR and the national death registry. We compared the hazard ratio (HR) of death and other endpoints between IGRT and non-IGRT groups. We performed supplementary analysis (SA) to evaluate the robustness of these results in a subgroup, taking an additional potential confounder into account. Our study population comprised of 586 patients that were balanced with regard to observed covariables. There was no significant difference in HR for death (0.99; 95% confidence interval 0.70-1.39; P=0.94) between IGRT and non-IGRT groups. There were also no significant differences in R0 resection, ILRR, IRCM, IOCM or ICVM. The results of our SA were consistent with these findings. For LARC patients treated with NCCRT, the treatment outcome was not significantly different among patients treated with and without IGRT. Further study is needed to clarify these results with consideration to additional potential confounding factors and toxicity profiles at endpoints.

Optimal radiation dosing in concurrent neoadjuvant chemoradiation for resectable esophageal cancer: a meta-analysis.

This is the first meta-analysis to study optimal radiation dose in the setting of concurrent neoadjuvant chemoradiotherapy (cnCRT) for esophageal cancer (EC). We sought to compare outcomes between high dose radiotherapy (HDRT) [>48.85 Gy biologically effective dose (BED)] group and low dose radiotherapy (LDRT) (≤48.85 Gy BED) for patients with EC receiving cnCRT. Medline, Embase, and Cochrane databases were searched independently by two members of our team on August 07, 2017. Articles were screened using Covidence. Study quality was assessed via CONSORT. Eligible studies had to be randomized controlled trials (RCT) comparing cnCRT vs. surgery alone in full-text English. Those with induction or sequential chemoradiotherapy were excluded. We captured data points including radiation dose, hazard ratios (HRs) for overall survival (OS), and treatment-related mortality (TRM). We analyzed HRs for OS and risk ratio (RR) for TRM and corresponding 95% confidence interval (CI) as the summary statistic. We used both fixed- and random-effects models in the presence of heterogeneity. The primary outcome was OS; secondary endpoint was treatment related mortality (TRM). We compared outcomes by HDRT vs. LDRT. To minimize chemotherapy heterogeneity, we performed a pre-planned analysis excluding the CROSS trial. The eleven included studies contained a total of 1,697 patients. Eight hundred forty-eight were randomized into the cnCRT. Of these 848 patients, 287 received HDRT and 561 received LDRT. HR for OS was not statistically different between LDRT (HR 0.67; 95% CI, 0.55-0.8) and HDRT (HR 0.68; 95% CI, 0.45-0.91). Excluding the CROSS trial, there was still no difference in outcomes between LDRT and HDRT. TRM was similar between LDRT and HDRT. With no difference in OS or TRM between LDRT and HDRT, 48.85 Gy BED cnCRT may be a sufficient radiation dose for cnCRT for patients with EC fit for surgery.

The prognostic significance of magnetic resonance imaging (MRI) following neoadjuvant concurrent chemoradiation (NCCR) in patients with locally advanced rectal adenocarcinoma (LARA).

e15166 Background: In patients with locally advanced rectal adenocarcinoma (LARA), the response to neoadjuvant concurrent chemoradiation (NCCR) correlates with long-term outcomes. Neoadjuvant rectal (NAR) score ([5 ypN - 3 (cT - ypT) + 12]2/9.61) is a novel short-term surrogate endpoint for disease free survival (DFS) and Overall survival (OS). The prognostic significance of magnetic resonance imaging (MRI) findings following NCCR is yet to be explored. Here, we evaluated the agreement between post NCCR MRI yT and yN and pathological ypT and ypN. In addition, we calculated the post NCCR MRI NAR (mNAR) score using the MRI yT and yN ([5 yN - 3 (cT - yT) + 12]2/9.61) and explored its prognostic significance. Methods: Between 2014 and 2018, all patients with LARA were identified. Among those, 43 patients received NCCR, had post NCCR MRI and underwent surgical resection. Weighted Kappa was used to measure the agreement between post NCCR MRI yT and yN and pathological ypT and ypN. Paired t-test was used to compare the means between NAR and mNAR scores. NAR and mNAR scores were classified as low ( < 8), intermediate (8-16) and high ( > 16). DFS and OS were analyzed using Kaplan-Meier curves. Results: In our cohort, the agreement was slight between post NCCR MRI yT and Pathological ypT (p = 0.111), and fair between post NCCR MRI yN and pathological ypN (0.278). The mean NAR score was 16 and the mean mNAR score was 20 (p = 0.0079). Low-intermediate and high NAR scores were seen in 31 (72%) and 12 (28%) patients respectively. However, low-intermediate and high mNAR scores were seen in 20 (47%) and 23 (53%) patients respectively. The median DFS in patients with low-intermediate and high NAR scores was not reached and 30 months (p = 0.00063) respectively. The median OS in patients with low-intermediate and high NAR scores was not reached and 40 months (p = 0.00056) respectively. The median DFS in patients with low-intermediate and high mNAR scores was not reached in both groups (p = 0.058). The median OS in patients with low-intermediate and high mNAR scores was not reached in both groups (p = 0.15). Conclusions: Post NCCR MRI yT and yN had slight and fair agreements with ypT and ypN respectively. In our cohort, there was a difference between NAR and mNAR. NAR demonstrated prognostic significance for DFS and OS, while mNAR did not at the time of analysis.

Phase II, prospective single-arm study of adjuvant pembrolizumab in N2 positive non-small cell lung cancer (NSCLC) treated with neoadjuvant concurrent chemoradiotherapy followed by curative resection: Preliminary results.

8520 Background: The standard treatment option for stage IIIA-N2 subgroup is still under discussion with controversies. We hypothesize that immune checkpoint inhibitor consolidation therapy could have an additional role in prolongation of the disease-free survival (DFS) for stage IIIA-N2 NSCLC treated with tri-modalities therapy. Methods: This is a phase 2 study evaluating the clinical efficacy of pembrolizumab treatment after CCRT with curative resection in stage IIIA-N2 NSCLC pts. Pathologically confirmed pts were treated with five cycles of CCRT, weekly paclitaxel (50mg/m2) and cisplatin (25mg/m2) combined with radiotherapy (total of 44Gy over 22 fractions) followed by curative resection. Adjuvant Pembrolizumab (200mg fixed dose) is applied every three weeks up to 2 years or until disease recurrence. The primary objective is disease-free survival of more than 20 months. The first patient was recruited in October 2017, and the data for this abstract was locked at 20th of January, 2019. Results: Total of 40 pts were screened, and 37 pts received treatment. Median age was 64 years (range 39-74), and twenty-three pts were male (62.2%). As a curative surgery, pts received lobectomy (n=34), bi-lobectomy (n=2), or pneumonectomy (n=1). Adenocarcinoma was predominant (n=27, 73.0%). After the neoadjuvant CCRT, down-staging were observed in nine pts (24.3%). The median follow-up duration was 10.6 months (range 3.1-17.2), and pts received a median of 11 cycles (range 1-22) of adjuvant pembrolizumab. DFS is not reached. Fourteen patients discontinued treatment due to disease progression (n=9), adverse events (n=4) and withdraw consent (n=1). There was a case of grade 4 pneumonitis and a case of grade 3 autoimmune hepatitis which lead to discontinuation of the treatment. Otherwise, grade 1-2 hypothyroidism (n=6), pneumonitis (n=5), skin rash (n=3) were observed. Patients with sever immune-related adverse event showed a significantly high percentage of Ki-67 + cells among CD8 T-cells in peripheral blood. Conclusions: This study is the first study to demonstrate the feasibility of adjuvant pembrolizumab monotherapy in stage IIIA-N2 patients. Updated and detail clinical and exploratory biomarker outcome will be presented at the annual meeting. Clinical trial information: NCT03053856.

Safety and efficacy of durvalumab following multimodality therapy for locally advanced esophageal and GEJ adenocarcinoma: Results from Big Ten Cancer Research Consortium study.

4058 Background: Concurrent chemoradiation (CRT) followed by esophagectomy is a standard of care for locally advanced esophageal (LA-EAC) and GEJ adenocarcinoma. Approximately 50% of patients (pts) experience disease relapse within the 1st yr after treatment(tx) completion. No adjuvant tx has been shown to improve survival in these pts. Immune checkpoint inhibitors have activity in metastatic PD-L1 positive EAC. Preclinical studies have shown upregulation of PD-1/PD-L1 pathway with RT +/- chemotherapy. Methods: We conducted a phase II trial evaluating safety and efficacy of durvalumab (durva), a monoclonal antibody against PD-L1, in pts with LA-EAC and GEJ adenocarcinoma who have viable tumor in surgical specimen after neoadjuvant CRT and R0 resection. Pts received durva 1500mg IV every 4 weeks for up to 1yr. Results: 24 pts were enrolled from 4/2016-1/2018 (median age: 60yrs (range, 43-70). 18 received carbo/paclitaxel and 6 received cis/5-FU concurrently with radiation. Staging at diagnosis: T2N0 (n=3, 12.5%), T2N2 (n=3, 12.5%),T3N0 (n=6, 25%), T3N1 (n=6, 25%), T3N2 (n=4, 17%), T3N3 (n=1, 4%), T3Nx (n=1, 4%).19 pts (79%) had positive lymph nodes (LNs) at the time of surgery following CRT. 12 pts completed 1yr of tx, 12 came off tx before 1yr because of relapse(6), AEs(5), and consent withdrawal (1). Median number of tx cycles was 12.5 (range, 2-13). Most common AEs were fatigue (n=8, 33.3%) and nausea (n=6, 25%). 3pts (12.5%) developed grade 3 irAEs: pneumonitis (1), hepatitis (1), colitis (1). At median follow up of 14.5 mo (range, 1.7-24mo), 17 are disease free (including 5 who came off tx before 1yr). 7pts (29%) have relapsed (3 alive, 4 died). 6/7pts had distant relapse (lung, brain, bone, cervical LNs) and 1 had locoregional relapse. 1-yr RFS and OS were 79.2% and 95.5%, respectively. 2-yr OS was 59.2%. RFS probability at 26 mo was 67.9%. Median survival after relapse was 11.1 mo (range, 0.1-11.3mo). Conclusions: Adjuvant durvalumab following trimodality therapy for LA-EAC and GEJ adenocarcinoma was safe and feasible with improvement in 1-yr RFS to 79.2% compared to historical rate of 50%. OS results are encouraging in this high risk pt population. Clinical trial information: NCT02639065.

10-year patient journey of stage III non-small cell lung cancer patients: A single-center, observational, retrospective study in Korea real-time automatically updated data warehouse in health care (UNIVERSE - ROOT study).

8536 Background: The current standard of care (SoC) for locally advanced stage III NSCLC is concurrent chemoradiotherapy (CCRT) but the outcomes are poor and unsatisfactory. The purpose of this study is to analyze the clinical features of patients with locally advanced lung cancer for 10 years in order to help develop future treatment strategy. Methods: This study through big data analysis retrospectively collected de-identified patient data from clinical data warehouse (CDW) using an unique algorithm with Standard Query Language (SQL). This new algorithm was developed by the close interactive collaboration between senior data scientists and medical oncologists. These algorithms include clinical natural language processing (NLP) systems that generate structured information from unstructured free text and structured data capture (SDC). We performed pre-processing work and data quality management (DQM) operation using over 700 clinical variables from 23,735 patients with NSCLC. Through data extraction, transformation, cleansing, and organization, we have developed a systematic and optimized program for lung cancer cohorts, including clinical features and molecular study and outcomes. It is also automatically updated every 24 hours in real time. Results: In the past 10 years, 23,735 patients were diagnosed with NSCLC and complete clinical data were available in 22,718 patients (95.7%). Out of total 22,718 patients 4,138 (18.2%) were diagnosed with stage III NSCLC. Among them, 2,676 patients (64.7%) received any type(s) of anti-cancer treatments or regular follow up at our institute. Of these 2,676 patients, 1,275 (47.6%) received curative surgery (+/- neo- and/or adjuvant CCRT); 685 (25.6%) patients definitive CCRT ; 220 (8.2%) patients palliative thoracic RT; 76 (2.8%) patients best supportive care. Median OS was 48.0 months for neoadjuvant CCRT followed by curative surgery, 51.8 months for curative surgery +/- adjuvant treatment, 29.4 months for unresected definitive CCRT (PFS 10.0 months (range: 9.1-10.9). Molecular profiles as well as updated clinical data will be presented. Conclusions: This unique in-house algorithm enables us to do a rapid and comprehensive analysis of the big data through CDW, which can be also automatically updated daily. This should provide clinically relevant information about real-world treatment outcomes and help implement or develop new treatment strategy in a timely manner.

116P - Study of pathological complete response rates with neoadjuvant concurrent chemoradiation with paclitaxel in locally advanced breast cancer

116P - Study of pathological complete response rates with neoadjuvant concurrent chemoradiation with paclitaxel in locally advanced breast cancer

The value of the planned neoadjuvant radiotherapy or chemoradiotherapy for the non-radical resection of esophageal squamous cell carcinoma

Objective: The role of planned neoadjuvant radiotherapy or chemoradiotherapy in the non-radical resection of esophageal squamous cell carcinoma was unclear. The study aimed to evaluate their therapeutic effect and analyze the prognostic factors. Methods: We retrospectively analyzed the clinical data of locally advanced esophageal squamous cell carcinoma who received neoadjuvant radio therapy (33 patients) and concurrent chemoradiotherapy (119 patients) from January 2004 to December 2016 in our single-institution database.The survival rates were calculated by Kaplan-Meier method. The prognostic factors were analyzed by using Log rank test and Cox proportional hazards model. Results: The median follow-up was 29.8 months. One hundred and one patients survived more than 3 years. The rates of overall survival (OS) and disease-free survival (DFS) at 3 years were 63.9% and 55.6%, respectively.The rates of complete, partial and minimal pathological response of the primary tumor were 50.3%, 38.4%, 11.3%, the corresponding 3-year OS were 75.5%, 57.4%, 27.3% (P<0.001) and 3-year DFS were 72.0%, 44.7%, 17.6% (P<0.001), respectively.The postoperative lymph node metastasis rate was 27.0%. The 3-year OS and DFS of the lymph node positive group was 45.6% and 32.8%, significantly lower than 70.8% and 63.7% of the negative group (both P<0.001). The 3-year OS and DFS of pathologic stage Ⅰ, Ⅱ, ⅢA, ⅢB and Ⅵ A were 76.2%, 57.4%, 64.7%, 35.0%, 33.3% (P<0.001) and 70.1%, 49.3%, 41.2%, 22.1%, 33.3% (P<0.001), respectively.The operation-related mortality was 3.3%. Multivariate analysis showed that chest pain, postoperative respiratory failure, pathological differentiation, more than 15 lymph node dissection and ypTNM stage were the independent prognostic factors of OS (P<0.05 for all). Conclusions: The planned neoadjuvant radiotherapy or chemoradiotherapy for the non-radical resection of advanced esophageal squamous cell carcinoma could result in favorable survival. The chest pain, postoperative respiratory failure, pathological differentiation, the number of lymph node resection and ypTNM stage are the independent prognostic factors of the prognosis of these patients.

Improved prognosis with induction chemotherapy in pathological complete responders after trimodality treatment for esophageal squamous cell carcinoma: Hypothesis generating for adjuvant treatment

PurposeTo compare the locations of recurrences and survival outcomes in esophageal squamous cell carcinoma (ESCC) patients with pathological complete response (pCR) after neoadjuvant concurrent chemoradiotherapy (CCRT) with or without preceding induction chemotherapy (IC) followed by esophagectomy. MethodsAmong 276 patients with locally advanced ESCC undergoing trimodality treatment during 2004–2014, 94 (34.1%) with pCR were eligible. The cohort included 26 patients undergoing IC before CCRT (IC group), and 68 patients who did not receive IC (non-IC group). ResultsAt a median follow-up of 51.4 months (95% confidence interval; 42.9–62.1), 19 patients experienced recurrences. There was a trend toward fewer distant failures in the IC group (0% vs.14.7%, p = 0.057), while locoregional recurrence was similar (7.7% vs. 7.4%). IC was associated with significantly improved survivals with the 5-year RFS and OS rates for the IC group of 85.1% and 90.5%, respectively, compared to of 46.2% and 48.1% for the non-IC group (p = 0.008 for RFS, and p = 0.015 for OS). By multivariable analyses, IC remained the only significant factor associated with survivals (HR:0.18 for RFS, p = 0.020 and HR:0.18 for OS, p = 0.025). The effect of IC in the whole cohort, irrespective of pathological response, was also assessed. Patients with non-pCR in the IC group had a trend toward worse survivals compared to the non-IC group ConclusionsIn ESCC patients with pCR after trimodality treatment, IC was associated with favorable survivals. The benefits of IC might be a hypothesis generation for adjuvant treatment for patients with pCR.

Preliminary clinical study of Nituzumab combined with neoadjuvant concurrent chemoradiotherapy for locally advanced esophageal squamous cell carcinoma

Objective To determine the treatment outcome of nimotuzumab in combination with neoadjuvant concurrent chemoradiotherapy followed by surgery for locally advanced esophageal squamous cell carcinoma (ESCC). Methods A total of 23 ESCC patients were enrolled. The preoperative strategies consisted of nimotuzumab (200 mg per week in week 1-5), concurrent chemotherapy by paclitaxel (45 mg/m2 per week in week 2-5) and cisplatin (20 mg/m2 per week in week 2-5) and radiotherapy by a total dose of 40 Gy (2. 0 Gy/d, 5 days per week in week 2-5). Esophagectomy was performed 4 weeks after the completion of preoperative therapies. Results All of the 23 patients enrolled completed the planned combined therapy method, and 22 patients underwent final surgery. The clinical response rate of nimotuzumab in combination with preoperative chemoradiotherapy was 96%. The most frequent Grade 1/2 toxicities observed were gastrointestinal reaction, bone marrow suppression, and esophagitis. The rate of radical resection was 100%, and the pathological complete response rate was 41%.The incidence rate of postoperative pulmonary infection, anastomotic leak, hoarseness, and arrhythmia were 14%, 9%, 4%, and 4%, respectively. No perioperative deaths occurred in our study. The 1-, 3-, and 5-year overall survival (OS) rate for all the patients were 86%, 52% and 52%, respectively. The median survival time (MST) was 28.9 months. Postoperative pathologic results showed 15 patients with lymph node negative and 7 patients with lymph node positive. the 1-, 3-, and 5-year OS for pN0 group were 100%, 62% and 62%, versus 57%, 29% and 29% for pN+ group (P=0.033). The MST for pN0 group was 42.6 months versus 14.2 months for pN+ group. Conclusions The regimen of nimotuzumab in combination with preoperative concurrent chemoradiotherapy followed by surgery is safe and effective for locally advanced ESCC. Patients with lymph node negative after surgery have significantly improved long-term survival. Key words: Esophageal neoplasms/targeted therapy; Esophageal neoplasms/radiochemotherapy; Treatment outcome

Effectiveness of Intensity-Modulated Radiotherapy for Rectal Cancer Patients Treated With Neoadjuvant Concurrent Chemoradiotherapy: A Population-based Propensity Score-matched Analysis.

Neoadjuvant concurrent chemoradiotherapy (nCCRT) is the standard of care for locally advanced rectal cancer (LARC) patients treated with neoadjuvant concurrent chemoradiotherapy (nCCRT). The aim of this study was to compare intensity-modulated radiotherapy (IMRT) to 3D conformal radiotherapy (3DCRT) in nCCRT patients. We identified LARC patients diagnosed from 2007 to 2015 through the Taiwan cancer registry (TCR) and we constructed a propensity score matched cohort to compare IMRT to 3DCRT after balancing observable potential confounders. We compared the hazard ratio (HR) of death as well as other endpoints between the IMRT and 3DCRT. We performed supplementary analysis (SA) when additional potential confounders were considered. Our study population consisted of 696 patients. There was no statistical difference when IMRT was compared to 3DCRT (HR for death=1.01, 95%confidence interval(CI)=0.76-1.35, p=0.93). There were also no statistical differences for the other endpoints or SA. For LARC patients treated with nCCRT, the treatment outcome has no statistically significant benefit between those treated with IMRT or 3DCRT.

Safety and efficacy of durvalumab following trimodality therapy for locally advanced esophageal and GEJ adenocarcinoma: Early efficacy results from Big Ten Cancer Research Consortium study.

5 Background: The standard of care for locally advanced esophageal adenocarcinoma(LA-EAC) is concurrent chemoradiation (CRT) followed by esophagectomy. Approximately 30% of patients (pts) achieve complete pathologic response (pCR) with this approach. The risk of relapse in the remaining 70% of pts is high, with 1-yr relapse free survival (RFS) of 50%. No adjuvant therapies have been shown to improve survival. Immune checkpoint inhibitors have activity in metastatic PD-L1 positive EAC. Preclinical studies have shown upregulation of PD-1 pathway with radiation +/- chemotherapy. Methods: We conducted a phase II study evaluating safety and efficacy of durvalumab (durva), a monoclonal antibody against PD-L1, in pts with LA-EAC and GE junction (GEJ) adenocarcinoma who do not achieve pCR after neoadjuvant CRT and R0 resection. Pts received durva 1500mg IV every 4 weeks for up to 1 yr after surgery. Primary objective was 1-yr RFS. Secondary objectives were incidence and severity of treatment related adverse events (AEs). Results: Twenty-four pts were enrolled from Apr 2016 to Jan 2018 (median age: 60yrs (range, 43-74)). Fourteen pts had GEJ adenocarcinoma and 10 had distal EAC. Eighteen received carboplatin/paclitaxel and six received cisplatin/5-FU concurrently with 50-50.4Gy radiation. Nineteen pts (79%) had positive lymph nodes at the time of surgery after neoadjuvant CRT, including three (12.5%) with N3, nine (37.5%) with N2, and seven (29%) with N1 disease. Among N0 pts, two had T3N0, one had T2N0, and two had T1N0 disease. At median follow-up of 11.7 mo (range 1.7-23.9 mo), seven pts (29%) have relapsed (five alive, two died); 17(67%) are disease free (six on treatment, seven completed treatment, three off-treatment); 1-yr and projected 26 mo RFS are 78.6% and 62.9%, respectively. Five pts (20.8%) developed grade 3 AEs: diarrhea (n = 1), hepatitis (n = 1), encephalopathy (n = 1), hyperglycemia (n = 1), hypoglycemia (n = 1). Most common grade 1 and 2 AEs were fatigue (33.3%), nausea (25.0%), and cough (20.8%). Conclusions: Adjuvant durva in pts with residual disease following trimodality therapy for EAC and GEJ adenocarcinoma is safe and feasible with 1-yr RFS of 78.6% compared to historical rate of 50%. Clinical trial information: NCT02639065.

Neoadjuvant nivolumab plus concurrent chemoradiation in stage II/III esophageal/gastroesophageal junction cancer.

142 Background: Neoadjuvant chemoradiation (cRT) prior to surgical resection in stage II/III esophageal/gastroesophageal junction (E/GEJ) cancer results in a complete pathologic response rate (pCR) of 20-30%. The appearance of favorable microenvironment features (enhanced tumor infiltrating lymphocytes, perivascular lymphocytes and tertiary lymphoid structures) after induction therapy in resected EC suggest early stage tumors may respond favorably to immune based therapy and in particular to PD-1 blockade when combined with cRT. Methods: In this pilot study, we administered 2 cycles of induction nivolumab (N) q2 weekly prior to standard of care carboplatin/paclitaxel/radiation plus 3 additional cycles of N on week 1, 3 and 5 of cRT. An Ivor-Lewis esophagectomy (E/MIE) was performed 6-10 weeks after the last IO dose. The primary endpoints of the study were safety and feasibility. We also evaluated the pCR, survival and temporal dynamics of T cell receptor clonotypes. Results: Between August 2017 and July 2018, 16 patients were enrolled on study. Induction N and neoadjuvant N combined with cRT in stage II/III E/GEJ cancers has an acceptable toxicity profile and was not associated with delays in surgery. Toxicities of note include steroid responsive grade 3 dermatitis (1/16), grade 3 hepatitis (1/16) and no cases of pneumonitis. To date, 10 patients with E adenocarcinoma have had an E/MIE and the pCR is 4/10 (40%). T cell receptor sequencing of the tumor bed and serial peripheral blood T cells revealed high peripheral representation of tumor-associated T cells. In one notable case, the highest-frequency intratumoral clone decreased in frequency in the peripheral blood upon treatment and rapidly increased after surgical resection, potentially signifying trafficking to the tumor site. Conclusions: Induction N and N combined with cRT has limited side-effects, did not result in surgical delay or enhanced surgical morbidity/mortality and induced a pCR of 40% in stage II/III E/GEJ cancers. Additional efficacy data on the full cohort and more in depth correlative studies will be presented to validate systemic activation of anti-tumor T cell responses. Clinical trial information: NCT03044613.

National trends in intensity modulated radiation therapy (IMRT) use for rectal cancer.

648 Background: Neoadjuvant chemoradiation represents the current standard of care for locally advanced rectal cancer prior to surgical resection. Traditionally, 3D conformal radiation therapy (3D CRT) was used in this setting. With advancing technology, intensity modulated radiation therapy (IMRT) was developed with the goal of delivering a more conformal radiation dose, with the potential for reduced toxicity providing a potential advantage across many disease sites. We sought to use the national cancer database (NCDB) to examine trends and predictors for IMRT use in rectal cancer. Methods: We queried the NCDB from 2004-2015 for patients with rectal adenocarcinoma treated with neoadjuvant concurrent chemoradiation to a standard doses (50.4-54Gy) followed by surgical resection. Odds ratios were used to determine predictors of IMRT use. Univariable and multivariable cox regressions were used to determine potential predictors of overall survival (OS). Propensity matching was used to account for any indication bias. Results: We identified 21,490 patients satisfying eligibility criteria, of which 3,131 were treated with IMRT. IMRT use increased from 1% in 2004 to 22% in 2014. Predictors for IMRT use included increased N stage, more recent treatment year, treatment at an academic facility, increased income, and higher educational level. On multivariable analysis including propensity score male gender, increased distance to facility, higher comorbidity score, IMRT technique, government insurance, African American race, and non-metro location were predictive of worse OS. Of note, the complete response rate at time of surgery was 28% with non-IMRT and 21% with IMRT. Conclusions: IMRT use has steadily increased in the treatment of rectal cancer, but still remains only a fraction of overall treatment technique. IMRT use correlated with worse survival likely due to utilization in higher stages and patients with worse disease features.

Placement of SurgiWrap® adhesion barrier film around the protective loop stoma after laparoscopic colorectal cancer surgery may reduce the peristomal adhesion severity and facilitate the closure.

A temporary loop stoma is often created after laparoscopic colorectal cancer surgery. Peristomal adhesions may make stoma closure into a complicated operation. We demonstrated how to place the SurgiWrap® adhesion barrier film and evaluated the peristomal adhesion severity and feasibility of stoma closure. This is a retrospective case-control study. Patients were divided into a study group (placement of adhesion barrier film) and a control group (no placement). Patient characteristics, operative data, and severity of adhesions were recorded. We used logistic regression to probe the association between the variables and the adhesion severity. A total of 180 patients were identified with 60 in the study group and 120 in the control group. In the study group, the adhesion severity (p < 0.001), operative time (p = 0.025), and time to flatus (p = 0.042) are significantly reduced. In logistic regression analysis, placement of the film (p < 0.001), neoadjuvant concurrent chemoradiotherapy (p = 0.041), and time interval between stoma creation and closure ≧12weeks (p = 0.038) are three significant factors influencing the peristomal adhesion. The placement of SurgiWrap® adhesion barrier film around the loop stoma after laparoscopic colorectal cancer surgery may reduce the peristomal adhesion severity and facilitate the stoma closure in terms of operative time and time to flatus.

Neoadjuvant concurrent chemoradiation in male breast cancer: Experience from a tertiary cancer center.

Male breast cancers (MBC) account for 1% of all breast cancers. Neoadjuvant concurrent chemoradiation (CTRT) is not the standard of care for treating breast cancer. However, in our center, it has been routinely used in patients with locally advanced breast cancer to downsize the tumor and make it amenable to surgery. This study was conducted to examine the clinical and pathological profile and outcomes of patients with MBC treated at our institute with neoadjuvant CTRT. The study was conducted at a tertiary cancer center and was retrospective in nature. All MBC patients treated with neoadjuvant CTRT at our center between 2001 and 2016 were enrolled in the study. Data were retrospectively extracted from the patients' case records. Kaplan-Meier method was used for survival analysis and the outcome variables were compared using the log-rank test. Thirty-one MBC patients who received neoadjuvant CTRT were analyzed in this study. The median age of the patients was 53 years. Stage IIB disease was observed in 8/31 (26%) patients, stage III in 20/31 (64%), and stage IV in 3/31 (10%) patients. There was no grade 3 or 4 toxicity due to CTRT. Surgery was performed in 29/31 (94%) patients and none of the patients had a pathological complete response. The median duration of follow-up was 95.3 months. The 8-year event-free survival and overall survival for stage IIB, III, and IV were 75%, 50%, and 0% and 87.5%, 69%, and 0%, respectively. This is the first study to report on the use of neoadjuvant CTRT in MBC. Prospective evidence from phase-3 randomized controlled trials on the safety and efficacy of CTRT in breast cancer is required before its routine use can be recommended.

To determine the utility of fluorodeoxyglucose-positron emission tomography-computed tomography scan in predicting pathological response in operated carcinoma rectum patients after initial neoadjuvant chemoradiation.

The objective of this study was to determine whether [18F]-fluorodeoxyglucose-positron emission tomography-computed tomography (FDG-PET CT) scan could predict the pathological response in carcinoma rectum patients after surgery in patients receiving neoadjuvant concurrent chemoradiotherapy (NACCRT). A prospective study was carried out from March 2015 to March 2017; 39 patients of histopathologically proven, locally advanced, potentially operable, of adenocarcinoma rectum were included in the study. Patients had a pretreatment FDG-PET-CT scan and repeat scan after 6-8 weeks of NACCRT. The change in mean maximum standardized uptake value ([%Δ SUVmax]) was compared with the tumor regression grade (TRG) in the postoperative histology. TRG of 1 and 2 was deemed responders and 3-5 was nonresponders. Chi-square test, one-way ANOVA, and receiver operating characteristics curve analysis were used. All analyses were done using SPSS 17.0 version. In 61.5% responders receiving NACCRT, the SUV fell from 10.91 ± 3.70 to 4.14 ± 1.73, respectively, while in 38.5% nonresponders, SUV fell from 11.65 ± 2.66 to 4.23 ± 1.3. SUV Δ% was 63.03 ± 10.17 in nonresponders and 61.32 ± 11.81 in responders with a nonsignificant P = 0.646. The P value did not reach a statistical significance as far as reduction in SUV values pre- and post-NACCRT is concerned in both responders as well as nonresponders. Hence, we concluded that assessment with FDG PET CT scan in carcinoma rectum patients' postneoadjuvant treatment cannot be the only imaging modality or assessing the response and postoperative histopathology remains the gold standard.

Impact of Clinicoepimiological Characteristics on the Outcome of Neo Adjuvant Concurrent Chemo Radiation in Locally Advanced Rectal Cancer Patients

Impact of Clinicoepimiological Characteristics on the Outcome of Neo Adjuvant Concurrent Chemo Radiation in Locally Advanced Rectal Cancer Patients