[Show abstract][Hide abstract] ABSTRACT: While trimodality therapy for esophageal cancer has improved patient outcomes, surgical complication rates remain high. The goal of this study was to identify modifiable factors associated with postoperative complications after neoadjuvant chemoradiation.
From 1998 to 2011, 444 patients were treated at our institution with surgical resection after chemoradiation. Postoperative (pulmonary, gastrointestinal [GI], cardiac, wound healing) complications were recorded up to 30 days postoperatively. Kruskal-Wallis tests and χ(2) or Fisher exact tests were used to assess associations between continuous and categorical variables. Multivariate logistic regression tested the association between perioperative complications and patient or treatment factors that were significant on univariate analysis.
The most frequent postoperative complications after trimodality therapy were pulmonary (25%) and GI (23%). Lung capacity and the type of radiation modality used were independent predictors of pulmonary and GI complications. After adjusting for confounding factors, pulmonary and GI complications were increased in patients treated with 3-dimensional conformal radiation therapy (3D-CRT) versus intensity modulated radiation therapy (IMRT; odds ratio [OR], 2.018; 95% confidence interval [CI], 1.104-3.688; OR, 1.704; 95% CI, 1.03-2.82, respectively) and for patients treated with 3D-CRT versus proton beam therapy (PBT; OR, 3.154; 95% CI, 1.365-7.289; OR, 1.55; 95% CI, 0.78-3.08, respectively). Mean lung radiation dose (MLD) was strongly associated with pulmonary complications, and the differences in toxicities seen for the radiation modalities could be fully accounted for by the MLD delivered by each of the modalities.
The radiation modality used can be a strong mitigating factor of postoperative complications after neoadjuvant chemoradiation.
International journal of radiation oncology, biology, physics 08/2013; 86(5):885-891. · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Body mass index (BMI) is a risk factor for comorbid illnesses and cancer development. It was hypothesized that obesity status affects disease outcomes and treatment-related toxicities in esophageal cancer patients treated with chemoradiotherapy (CRT). From March 2002 to April 2010, 405 patients with non-metastatic esophageal carcinoma at MD Anderson Cancer Center treated with either definitive or neoadjuvant CRT were retrospectively analyzed. Patients were categorized as either obese (BMI ≥ 25 kg/m(2) ) or nonobese (BMI < 25 kg/m(2) ). Progression-free survival and overall survival times were examined using the Kaplan-Meier method and Cox proportional hazards regression analysis. One hundred fifteen (28.4%) patients were classified as nonobese and 290 (71.6%) as obese. Obese patients were more likely than others to have several comorbid diseases (P < 0.001), adenocarcinoma located distally (P < 0.001), and have undergone surgery (P = 0.004). Obesity was not associated with either worse operative morbidity/mortality (P > 0.05) or worse positron emission tomography tumor response (P = 0.46) on univariate analysis, nor with worse pathologic complete response (P = 0.98) on multivariate analysis. There was also no difference in overall survival, locoregional control, or metastasis-free survival between obese and nonobese patients (P = 0.86). However, higher BMI was associated with reduced risk of chemoradiation-induced high-grade esophagitis (P = 0.021), esophageal stricture (P < 0.001), and high-grade hematologic toxicity (P < 0.001). In esophageal cancer patients treated with CRT, obesity is not predictive of poorer disease outcomes or operative morbidities; instead, data suggest it may be associated with decreased risk of acute chemotherapy- and radiotherapy-related treatment toxicities.
Diseases of the Esophagus 04/2013; · 1.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: Although 3-dimensional conformal radiotherapy (3D-CRT) is the worldwide standard for the treatment of esophageal cancer, intensity modulated radiotherapy (IMRT) improves dose conformality and reduces the radiation exposure to normal tissues. We hypothesized that the dosimetric advantages of IMRT should translate to substantive benefits in clinical outcomes compared with 3D-CRT. METHODS AND MATERIALS: An analysis was performed of 676 nonrandomized patients (3D-CRT, n=413; IMRT, n=263) with stage Ib-IVa (American Joint Committee on Cancer 2002) esophageal cancers treated with chemoradiotherapy at a single institution from 1998-2008. An inverse probability of treatment weighting and inclusion of propensity score (treatment probability) as a covariate were used to compare overall survival time, interval to local failure, and interval to distant metastasis, while accounting for the effects of other clinically relevant covariates. The propensity scores were estimated using logistic regression analysis. RESULTS: A fitted multivariate inverse probability weighted-adjusted Cox model showed that the overall survival time was significantly associated with several well-known prognostic factors, along with the treatment modality (IMRT vs 3D-CRT, hazard ratio 0.72, P<.001). Compared with IMRT, 3D-CRT patients had a significantly greater risk of dying (72.6% vs 52.9%, inverse probability of treatment weighting, log-rank test, P<.0001) and of locoregional recurrence (P=.0038). No difference was seen in cancer-specific mortality (Gray's test, P=.86) or distant metastasis (P=.99) between the 2 groups. An increased cumulative incidence of cardiac death was seen in the 3D-CRT group (P=.049), but most deaths were undocumented (5-year estimate, 11.7% in 3D-CRT vs 5.4% in IMRT group, Gray's test, P=.0029). CONCLUSIONS: Overall survival, locoregional control, and noncancer-related death were significantly better after IMRT than after 3D-CRT. Although these results need confirmation, IMRT should be considered for the treatment of esophageal cancer.
International journal of radiation oncology, biology, physics 08/2012; · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Proton beam therapy (PBT) is a promising modality for the management of thoracic malignancies. We report our preliminary experience of treating esophageal cancer patients with concurrent chemotherapy (CChT) and PBT (CChT/PBT) at MD Anderson Cancer Center.
This is an analysis of 62 esophageal cancer patients enrolled on a prospective study evaluating normal tissue toxicity from CChT/PBT from 2006 to 2010. Patients were treated with passive scattering PBT with two- or three-field beam arrangement using 180 to 250 MV protons. We used the Kaplan-Meier method to assess time-to-event outcomes and compared the distributions between groups using the log-rank test.
The median follow-up time was 20.1 months for survivors. The median age was 68 years (range, 38-86). Most patients were males (82%) who had adenocarcinomas (76%) and Stage II-III disease (84%). The median radiation dose was 50.4 Gy (RBE [relative biologic equivalence]) (range, 36-57.6). The most common grade 2 to 3 acute toxicities from CChT/PBT were esophagitis (46.8%), fatigue (43.6%), nausea (33.9%), anorexia (30.1%), and radiation dermatitis (16.1%). There were two cases of grade 2 and 3 radiation pneumonitis and two cases of grade 5 toxicities. A total of 29 patients (46.8%) received preoperative CChT/PBT, with one postoperative death. The pathologic complete response (pCR) rate for the surgical cohort was 28%, and the pCR and near CR rates (0%-1% residual cells) were 50%. While there were significantly fewer local-regional recurrences in the preoperative group (3/29) than in the definitive CChT/PBT group (16/33) (log-rank test, p = 0.005), there were no differences in distant metastatic (DM)-free interval or overall survival (OS) between the two groups.
This is the first report of patients treated with PBT/CChT for esophageal cancer. Our data suggest that this modality is associated with a few severe toxicities, but the pathologic response and clinical outcomes are encouraging. Prospective comparison with more traditional approach is warranted.
International journal of radiation oncology, biology, physics 03/2012; 83(3):e345-51. · 4.59 Impact Factor