Cheng Nang Leong

Outcomes of Adjuvant Chemoradiotherapy After a Radical Gastrectomy and a D2 Node Dissection for Gastric Adenocarcinoma

Purpose:Intergroup 0116 (INT-0116) established adjuvant chemoradiation as the standard of care for resected high-risk adenocarcinoma of the stomach in the United States. However, adjuvant chemoradiation remains controversial in many parts of Asia and Europe, where patients tend to undergo a more thorough D2 dissection. In INT-0116, 90% of patients had a limited or inadequate node dissection (D0 or D1). Also, 17% of patients in the chemoradiation arm had to discontinue treatment because of toxicities. The objectives of this retrospective study are to report the clinical outcomes of a cohort of patients who were mostly treated with a D2 node dissection and received adjuvant chemoradiation as per INT-0116, and the toxicities of chemoradiation in the context of more aggressive surgery. Methods:After the results of INT-0116 became apparent, we adopted an institutional policy whereby patients who would otherwise fit the inclusion criteria of INT-0116 received adjuvant chemoradiation. Between March 1999 and November 2004, 70 consecutive patients with pathologic stage T3, T4, or node-positive disease were treated according to the chemoradiation arm of INT-0116. Patients received intravenous 5-fluorouracil 425 mg/m2 and leucovorin 20 mg/m2 in cycles 1, 3, and 4. Concurrent chemoradiation was given in cycle 2 and consisted of bolus 5-fluorouracil and leucovorin and radiotherapy (45 Gy over 25 fractions in 5 weeks). All patients were operated on by dedicated Japan-trained Surgical Oncologists. Results:Sixty-seven patients (96%) had a D2 nodal dissection. Sixty-five patients (93%) had negative pathologic margins (R0 resection) and 5 (7%) had microscopically involved margins (R1 resection). The median follow-up was 27 months (range, 10.1–60.3). The 3-year overall survival, disease-free survival, and local control were 60.6%, 54.1%, and 84.3%, respectively. Of the 30 patients who relapsed, 5 (17%) had isolated locoregional recurrences only. The National Cancer Institute – Common Terminology Criteria version 3.0 acute grade 3 or 4 gastrointestinal and hematological toxicity rates were 15.7% and 4.3%, respectively. Toxicities led to chemotherapy dose-reductions in 18 patients and dose-delay in 19 patients. Including chemotherapy dose-reductions and delays, 66 patients (94%) completed the entire chemoradiation regimen. There were no toxicity-related deaths. Conclusion:In our cohort of 70 patients who had a more thorough D2 node dissection, adjuvant chemoradiation was well tolerated with acceptable toxicities and reasonable tumor control.

Clinical outcome of palliative radiotherapy for locally advanced symptomatic gastric cancer in the modern era.

AbstractThe purpose of this study was to report the outcomes of patients with symptomatic locally advanced/recurrent gastric cancer treated with radiotherapy (RT) using modern 3-dimensional conformal techniques.We retrospectively reviewed patients who had palliative RT for index symptoms of gastric bleeding, pain, and obstruction. Study endpoints included symptom response, median survival, and treatment toxicity.Of 115 patients with median age of 77 years, 78 (67.8%) patients had metastatic disease at the time of treatment. Index symptoms were gastric bleeding, pain, and obstruction in 89.6%, 9.2%, and 14.3% of patients, respectively. Dose fractionation regimen ranged from 8-Gy single fraction to 40 Gy in 16 fractions. One hundred eleven patients (93.3%) were computed tomography (CT) planned. Median follow-up was 85 days. Response rates for bleeding, pain, and obstruction were 80.6% (83/103), 45.5% (5/11), and 52.9% (9/17), respectively, and median duration of response was 99 days, 233 days, and 97 days, respectively. Median survival was 85 days. Actuarial 12-month survival was 15.3%. There was no difference in response rates between low (⩽39 Gy) and high (>39 Gy) biologically effective dose (BED) regimens (&agr;/&bgr; ratio = 10). Median survival was significantly longer in patients who responded to RT compared with patients who did not (113.5 vs 47 days, P < 0.001). Three patients (2.6%) had grade 3 Common Toxicity Criteria equivalent toxicity (nausea/vomiting/anorexia).External beam RT delivered using 3-dimensional conformal techniques is highly effective and well tolerated in the local palliation of gastric cancer, with palliation lasting the majority of patient’s lives. Short (⩽39 Gy BED) RT schedules are adequate for effective symptom palliation. A phase II study of palliative gastric RT is ongoing.

Palliative radiotherapy for gastric cancer: a systematic review and meta-analysis

Background/Purpose To review the efficacy and toxicity of palliative radiotherapy (RT) for symptomatic locally advanced gastric cancer (GC) and to determine the optimal RT schedule for symptom palliation. Methods We searched MEDLINE and CENTRAL for eligible studies published from 1995 to 2015. Outcomes of interest were relief of bleeding, pain and obstruction. RESULTS Seven non-comparative observational studies were included. There were large variations in RT dose and fractionation. The pooled overall response rates for bleeding, pain and obstruction symptoms were 74%, 67% and 68% respectively. There was no difference in response rate of bleeding between regimens with high biological equivalent dose (BED) of = 39Gy versus regimens with low BED<39Gy regimens (p value =0.39). Grade 3 to 4 toxicities occurred in up to 15% of patients for patients treated with RT alone and up to 25% of patients treated with chemoradiotherapy. Health-related quality of life (HRQL) outcomes were not reported. Conclusion More than two-thirds of patients receiving RT would have a clinical benefit. Low BED regimens appear to be adequate for symptom palliation. Toxicity rates appear acceptable for patients treated with RT alone. The optimal dose fractionation regimen for symptom palliation remains unclear. Prospective studies to determine the effects of palliative gastric RT on HRQL outcomes are warranted.

A phase II trial of preoperative concurrent chemotherapy and dose escalated intensity modulated radiotherapy (IMRT) for locally advanced rectal cancer

Objectives: To determine the pathological response rates and toxicity and in patients with locally advanced rectal cancer treated with concurrent capecitabine and dose escalated intensity modulated radiotherapy (IMRT) Methods: Patients with stage II or III adenocarcinoma of the rectum were treated with preoperative concurrent capecitabine and IMRT. Dose of capecitabine was 825mg/m2, 5 days a week for 5 weeks. IMRT was used to deliver a dose of 45Gy in 25 fractions (1.8Gy per fraction daily, 5 days a week over 5 weeks) to the regional lymphatics and areas at risk of harbouring microscopic disease. A concomitant synchronous integrated boost (SIB) to the gross tumour with a margin to a total dose of 55Gy in 25 fractions was also delivered in the same period. TME surgery was performed 8 weeks after preoperative therapy. The primary endpoint is pathological complete response rate (pCR) and the secondary endpoint was downstaging rates, Sphincter preservation rates (SPR), disease free survival (DFS) at 2 years and toxicity graded using the CTCAE v3.0. Results: Twenty three patients were enrolled. Three were not evaluable; one did not complete treatment due to logistic issues and two declined surgery. The remaining 20 patients completed preoperative chemoIMRT followed by TME surgery. At a median follow-up of 38.2 months (17.5-53.2 months), 90% (18 of 20) patients were alive. The 2 year overall survival and DFS were 90% and 90% respectively. 35%(7/20) of patients had a pCR. 65% (13 of 20) patients had successful downstaging of their rectal tumours. There was no local recurrence. Sphincter preservation rate was 85%. Treatment was well tolerated with only one patient (5%) having Grade 3 radiation proctitis. Conclusions: Preoperative concurrent capecitabine and dose escalated IMRT is well tolerated and results in high rates of pCR. A randomized trial comparing this regimen with standard 3D conformal chemoradiotherapy is warranted.

Association between radiation heart dosimetric parameters, myocardial infarct and overall survival in stage 3 non-small cell lung cancer treated with definitive thoracic radiotherapy

OBJECTIVES The aim of this retrospective observational study is to assess the association between various radiation heart dosimetric parameters (RHDPs) and acute myocardial infarct (AMI) and overall survival (OS) outcomes in stage III non-small cell lung cancer (NSCLC) treated with definitive radiotherapy with or without chemotherapy. MATERIALS AND METHODS We identified eligible patients treated at two institutions from 2007 to 2014. We linked their electronic medical records to the national AMI and death registries. We performed univariable and multivariable Cox regressions analysis to assess the association between various RHDPs, AMI and OS. RESULTS 120 eligible patients were included with a median follow-up of 17.6 months. Median age was 65.5 years. Median prescription dose was 60 Gy. Median mean heart dose (MHD) was 12.6 Gy. Univariable analysis showed that higher MHD (hazard ratio (HR), 1.03; 95% confidence interval (CI), 1.01-1.06; P = .008) and volume of heart receiving at least 5 Gy (V5) (HR, 1.01; 95% CI, 1.00-1.03; P = .042) were associated with increased hazards for AMI. Univariable analysis showed that higher MHD, V5, V25, V30, V40, V50 and dose to 30% of heart volume were associated with increased hazards for death. Multivariable analysis showed that there was no statistically significant association between various RHDPs and OS. CONCLUSION The incidence of AMI is low among stage III NSCLC treated with definitive radiotherapy with or without chemotherapy. There is insufficient evidence to conclude that RHDPs are associated with AMI or OS in our study.

Impact of epidermal growth factor receptor sensitizing mutations on outcomes of patients with non-small cell lung cancer treated with definitive thoracic radiation therapy: a systematic review and meta-analysis

Background To determine if the presence of epidermal growth factor receptor (EGFR) sensitizing mutations improves tumor control and survival outcomes in patients with non-metastatic non-small cell lung cancer (NSCLC) who received definitive thoracic radiation therapy (TRT) with or without chemotherapy. Materials and Methods We searched MEDLINE for eligible comparative studies which compared the outcomes of patients treated with definitive TRT according to EGFR mutation status. Meta-analysis was performed using random effects model. Outcomes of interest were tumor overall response rate (ORR), loco-regional (LRR), distant recurrence rates (DRR), relapse-free survival (RFS), overall survival (OS) and adverse events (AE). Results We found seven studies including 537 patients with stage III NSCLC. Up to 45% of patients in the studies had mutations in exon 19 and 21. Patients harbouring EGFR sensitizing mutations had a trend towards improvement in ORR (risk ratio 1.17, 95% confidence interval 0.99–1.37, P = 0.06) compared to EGFR wild type status. There were no significant differences in LRR, DRR, RFS, OS and AE outcomes between the EGFR mutant and EGFR wild type groups. Conclusions The presence of EGFR sensitizing mutations may improve tumour response rate but not survival in patients with localized NSCLC treated with definitive thoracic radiation therapy with or without chemotherapy.