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Propensity score-based comparison of long-term outcomes with 3-dimensional conformal radiotherapy vs intensity-modulated radiotherapy for esophageal cancer.

ABSTRACT: 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.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.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).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.

SUBMITTER: Lin SH

PROVIDER: S-EPMC3923623 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Propensity score-based comparison of long-term outcomes with 3-dimensional conformal radiotherapy vs intensity-modulated radiotherapy for esophageal cancer.

Lin Steven H SH Wang Lu L Myles Bevan B Thall Peter F PF Hofstetter Wayne L WL Swisher Stephen G SG Ajani Jaffer A JA Cox James D JD Komaki Ritsuko R Liao Zhongxing Z

International journal of radiation oncology, biology, physics 20120803 5

<h4>Purpose</h4>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.<h4>Methods and materials</h4>An analysis was performed of 676 nonrandomized patients (3D-CRT, n=413; IM ...[more]

PMID: 22867894

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Project description:Although a large number of influential studies that have been conducted worldwide on locally advanced esophageal cancer (EC) have employed the treatment modality of three-dimensional conformal radiotherapy (3D-CRT), an advanced as well as highly conformal technology known as intensity-modulated radiotherapy (IMRT) has attracted increasing attention from the radiotherapy research community. This is because of the clear advantages of IMRT, including decrease in radiation dose that reaches critical cardiopulmonary organs. These two treatment modalities need to be investigated with regard to their effect on local control rate and patient survival. In addition, related clinical factors also need to be explored. Data from a total of 431 patients with locally advanced EC, who underwent radiation therapy between January 1, 2010 and December 31, 2013, were included in the present study. Two hundred and ninety-three patients received 3D-CRT, while 138 patients received IMRT. We constructed propensity score matches to make the two groups be comparable (136 patients in 3D-CRT group and 138 patients in IMRT group. Kaplan-Meier analysis was conducted to evaluate the endpoint of overall survival (OS). A Cox proportional hazards model was employed to analyze the relationship between the associated factors and the outcomes via univariate and multivariate approaches. The mean follow-up period was 36.2 months, and the median follow-up period was 23 months. For the IMRT group, the median OS was 31 months, and the 1-, 3-, and 5-year OS rates were 70.3%, 50.0%, and 42.8%, respectively, while for the 3D-CRT group, the median OS was 22 months, and the 1-, 3-, and 5-year OS rates were 63.2%, 41.0%, and 35.4%, respectively (p < 0.05). The univariate analysis revealed that quit drinking, chemotherapy, and concurrent chemotherapy were significant risk factors for the prognosis of EC (p < 0.05), as well as the radiation therapy technique used (p=0.052). The multivariate analysis indicated that chemotherapy and quit drinking were independent predictive factors for OS. OS is found to be significantly better in the IMRT group, compared with that of the 3D-CRT group. Even though these outcomes need further validation, IMRT should be considered preferentially as a therapeutic option for EC, in combination with chemotherapy and persuading patients to quit drinking.

Project description:BackgroundThough the vast majority of seminal trials for locally advanced esophageal cancer (EC) utilized three-dimensional conformal radiotherapy (3DCRT), the advanced and highly conformal technology known as intensity-modulated radiotherapy (IMRT) can decrease doses to critical cardiopulmonary organs. To date, there have been no studies comparing both modalities as part of definitive chemoradiation (dCRT) for EC. Herein, we investigated local control and survival and evaluated clinical factors associated with these endpoints between cohorts.MethodsWe retrospectively analyzed 93 patients (3DCRT n = 49, IMRT n = 44) who received dCRT at our institution between 2000 and 2012 with the histologic diagnosis of nonmetastatic EC, a Karnofsky performance status of ≥70, curative treatment intent, and receipt of concomitant CRT. Patients were excluded if receiving <50 Gy. Kaplan-Meier analysis was used to evaluate the endpoints of local relapse rate (LR), progression-free survival (PFS), and overall survival (OS). Cox proportional hazards modeling addressed factors associated with outcomes with univariate and multivariate approaches. Rates of acute toxicities and basic dosimetric parameters were compared between 3DCRT and IMRT patients.ResultsMean follow-up was 34.7 months. The 3-year LR was 28.6% in the 3DCRT group and 22.7% in the IMRT group (p = 0.620). Median PFS were 13.8 and 16.6 months, respectively (p = 0.448). Median OS were 18.4 and 42.0 months, respectively (p = 0.198). On univariate analysis, only cumulative radiation dose was associated with superior LR (hazard ratio (HR) 0.736; 95% confidence interval (CI) 0.635 - 0.916, p = 0.004). Factors clearly affecting survival were not observed.ConclusionsWhen comparing 3DCRT- versus IMRT-based dCRT, no survival benefits were observed. However, we found a lower local recurrence rate in the IMRT group potentially owing to dose-escalation. Prospective data are needed to verify the presented results herein.

Project description:BACKGROUND:This was a prespecified secondary analysis of a randomized trial that analyzed bone density and pain response following fractionated intensity-modulated radiotherapy (IMRT) versus three-dimensional conformal radiotherapy (3DCRT) for palliative management of spinal metastases. METHODS/MATERIALS:Sixty patients were enrolled in the single-institutional randomized exploratory trial, randomly assigned to receive IMRT or 3DCRT (30 Gy in 10 fractions). Along with pain response (measured by the Visual Analog Scale (VAS) and Chow criteria), quantitative bone density was evaluated at baseline, 3, and 6 months in both irradiated and unirradiated spinal bodies, along with rates of pathologic fractures and vertebral compression fractures. RESULTS:Relative to baseline, bone density increased at 3 and 6 months following IMRT by a median of 24.8% and 33.8%, respectively (p?<?0.01 and p?=?0.048). These figures in the 3DCRT cohort were 18.5% and 48.4%, respectively (p?<?0.01 for both). There were no statistical differences in bone density between IMRT and 3DCRT at 3 (p?=?0.723) or 6 months (p?=?0.341). Subgroup analysis of osteolytic and osteoblastic metastases showed no differences between groups; however, mixed metastases showed an increase in bone density over baseline in the IMRT (but not 3DCRT) arm. The 3-month rate of the pathological fractures was 15.0% in the IMRT arm vs. 10.5% in the 3DCRT arm. There were no differences in pathological fractures at 3 (p?=?0.676) and 6 (p?=?1.000) months. The IMRT arm showed improved VAS scores at 3 (p?=?0.037) but not 6 months (p?=?0.430). Using Chow criteria, pain response was similar at both 3 (p?=?0.395) and 6 (p?=?0.732) months. CONCLUSIONS:This the first prospective investigation evaluating the impact of IMRT vs. 3DCRT on bone density. Along with pain response and pathologic fracture rates, significant rises in bone density after 3 and 6 months were similar in both cohorts. Future randomized investigations with larger sample sizes are recommended. TRIAL REGISTRATION:NCT, NCT02832830 . Registered 14 July 2016.

Project description:PURPOSE:To compare long-term disease-related outcomes and late radiation morbidity between intensity-modulated radiation therapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) in head and neck squamous cell carcinoma (HNSCC) in the setting of a prospective randomized controlled trial. METHODS:Previously untreated patients with early to moderately advanced non-metastatic squamous carcinoma of the oropharynx, larynx, or hypopharynx (T1-T3, N0-N2b, M0) planned for comprehensive irradiation of primary site and bilateral neck nodes were randomly assigned to either IMRT or 3D-CRT after written informed consent. Patients were treated with 6MV photons to a total dose of 70Gy/35 fractions over 7?weeks (3D-CRT) or 66Gy/30 fractions over 6?weeks (IMRT). A sample size of 60 patients was estimated to demonstrate 35% absolute difference in the incidence of ?grade 2 acute xerostomia between the two arms. All time-to-event outcomes were calculated from date of randomization until the defined event using the Kaplan-Meier method. RESULTS:At a median follow-up of 140?months for surviving patients, 10-year Kaplan-Meier estimates of loco-regional control (LRC); progression-free survival (PFS); and overall survival (OS) with 95% confidence interval (95%CI) were 73.6% (95%CI: 61.2-86%); 45.2% (95%CI: 32-58.4%); and 50.3% (95%CI: 37.1-63.5%) respectively. There were no significant differences in 10-year disease-related outcomes between 3D-CRT and IMRT for LRC [79.2% (95%CI: 62.2-96.2%) vs 68.7% (95%CI: 51.1-86.3%), p =?0.39]; PFS [41.3% (95%CI: 22.3-60.3%) vs 48.6% (95%CI: 30.6-66.6%), p =?0.59]; or OS [44.9% (95%CI: 25.7-64.1%) vs 55.0% (95%CI: 37-73%), p =?0.49]. Significantly lesser proportion of patients in the IMRT arm experienced ?grade 2 late xerostomia and subcutaneous fibrosis at all time-points. However, at longer follow-up, fewer patients remained evaluable for late radiation toxicity reducing statistical power and precision. CONCLUSIONS:IMRT provides a clinically meaningful and sustained reduction in the incidence of moderate to severe xerostomia and subcutaneous fibrosis compared to 3D-CRT without compromising disease-related outcomes in long-term survivors of non-nasopharyngeal HNSCC.

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Propensity score-based comparison of long-term outcomes with 3-dimensional conformal radiotherapy vs intensity-modulated radiotherapy for esophageal cancer.

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Propensity score-based comparison of long-term outcomes with 3-dimensional conformal radiotherapy vs intensity-modulated radiotherapy for esophageal cancer.

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