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Aim: To evaluate the role of radiotherapy (RT) in the treatment of localized primary adult rhabdomyosarcoma (RMS). Methods: This retrospective study identified 62 consecutive adult patients with localized primary RMS from January 2000 and July 2016. Local failure‐free survival (LFFS), distant metastasis‐free survival (DMFS) and overall survival (OS) were analyzed by the Kaplan–Meier method. Multivariate Cox proportional hazards regression models were fit to assess the ability of patient characteristics to predict survival. Results: With a median follow‐up of 33 months (range, 6–195 months), the 5‐year LFFS, DMFS and OS of all patients were 64.0%, 50.0% and 45.0%, respectively. RT was administered to 28 patients (45.2%). Patients who received RT had a higher 5‐year LFFS (81.7% vs 47.2%), 5‐year DMFS (59.4% vs 43.1%) and 5‐year OS (57.1% vs 34.8%) compared with patients who did not received RT. In mulitvariate analysis, RT retained significance as an independent predictor of improved LFFS [hazard ratio (HR) = 0.282; 95% confidence interval (CI), 0.095–0.838; P = 0.023], DMFS (HR = 0.289; 95% CI, 0.125–0.991; P = 0.004) and OS (HR = 0.334; 95% CI, 0.153–0.727; P = 0.006). Conclusions: RT significantly reduced local recurrence, distant metastasis and tumor mortality compared with no radiotherapy for localized primary adult RMS. [ABSTRACT FROM AUTHOR]

Abstract: Aim: The aim of this study was to determine the effect of local recurrence on overall survival in patients with intermediate high‐grade localized primary soft tissue sarcoma (STS) of extremity and abdominothoracic wall. Methods: This retrospective study identified 133 consecutive patients with intermediate high‐grade localized primary STS of extremity and abdominothoracic wall from January 2000 to July 2010. Survival curves were constructed by the Kaplan–Meier method and log‐rank test was used to assess statistical significance. Hazard ratios (HRs) were calculated based on multivariable Cox logistic regression method. Results: The 5‐year cumulative incidence of local recurrence was 26.0% with a median follow‐up of 68 months (range, 5–127 months). The univariate analysis showed that local recurrence was associated with decreased overall survival, with 5‐year overall survival of 80.5% and 53.6% in the no local recurrence patients and local recurrence patients, respectively (P = 0.001). The multivariate analysis demonstrated that local recurrence was a negative prognostic factor for overall survival (HR = 2.115, 95% confidence interval [CI] 1.036–4.319, P = 0.040). Radiotherapy significantly reduced local recurrence compared with surgery alone (HR = 0.387, 95% CI 0.180–0.877, P = 0.019), while larger tumor size (HR = 3.184, 95% CI 1.351–7.506 P = 0.008) was correlated with higher rate of local recurrence. Conclusion: Local recurrence in patients with intermediate high‐grade localized primary STS is associated with decreased overall survival. [ABSTRACT FROM AUTHOR]

Purpose: Radiation therapy (RT) for left-sided breast cancer has been associated with cardiac dysfunction. We herein assess the temporal nature and volume dependence of RT-induced left ventricular perfusion defects and whether these perfusion defects are related to changes in cardiac wall motion or alterations in ejection fraction. Methods: From 1998 to 2001, 114 patients were enrolled onto an IRB-approved prospective clinical study to assess changes in regional and global cardiac function after RT for left-sided breast cancer. Patients were imaged 30 to 60 minutes after injection of technetium 99m sestamibi or tetrofosmin. Post-RT perfusion scans were compared with the pre-RT studies to assess for RT-induced perfusion defects as well as functional changes in wall motion and ejection fraction. Two-tailed Fisher's exact test and the Cochran-Armitage test for linear trends were used for statistical analysis. Results: The incidence of new perfusion defects 6, 12, 18, and 24 months after RT was 27%, 29%, 38%, and 42%, respectively. New defects occurred in approximately 10% to 20% and 50% to 60% of patients with less than 5%, and greater than 5%, of their left ventricle included within the RT fields, respectively (p = 0.33 to 0.00008). The rates of wall motion abnormalities in patients with and without perfusion defects were 12% to 40% versus 0% to 9%, respectively; p values were 0.007 to 0.16, depending on the post-RT interval. Conclusions: Radiation therapy causes volume-dependent perfusion defects in approximately 40% of patients within 2 years of RT. These perfusion defects are associated with corresponding wall-motion abnormalities. Additional study is necessary to better define the long-term functional consequences of RT-induced perfusion defects. [ABSTRACT FROM AUTHOR]

Background: Primary squamous cell carcinoma of the breast (PSCCB) is a rare clinical classification of breast tumors. Little is known about its clinicopathological features, prognosis and potential therapeutic strategies. The purpose of this study is to evaluate the effect of postoperative radiotherapy (PORT) on patients with squamous cell carcinoma (SCC) of the breast. Methods: We retrospectively analyzed patients diagnosed with PSCCB in our center. All pathological slides were reviewed by an experienced pathologist to confirm the diagnosis. Furthermore, we searched the public database for patients with SCC of the breast. Then, we analyzed the clinicopathological features, treatment methods and patient outcomes. Results: We identified 14 patients with primary SCC of the breast in our center. Additionally, 739 patients with SCC of the breast from the Surveillance, Epidemiology and End Results (SEER) database were diagnosed between 1975 and 2016. Only 453 patients who underwent surgery were included in this study. Patients from the SEER database had a more advanced tumor node metastasis (TNM) stage than patients from our center. The median overall survival (OS) of all patients was 104 months (95% confidence interval [CI], 87.2–120.8 months), and the 5‐year OS was 60.8% (95% CI, 56.1%–65.5%). Most of the patients (58%) tested negative for hormonal receptor expression. Multivariate analysis showed that PORT was an independent prognostic factor for OS. Conclusion: The results of our study demonstrate that SCC of the breast presents aggressive behavior with unique clinical characteristics. PORT improved OS significantly in patients with SCC of the breast. Longer‐term studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to assess the impact of patient-specific factors, left ventricle (LV) volume, and treatment set-up errors on the rate of perfusion defects 6 to 60 months post–radiation therapy (RT) in patients receiving tangential RT for left-sided breast cancer. Methods and Materials: Between 1998 and 2005, a total of 153 patients were enrolled onto an institutional review board–approved prospective study and had pre- and serial post-RT (6–60 months) cardiac perfusion scans to assess for perfusion defects. Of the patients, 108 had normal pre-RT perfusion scans and available follow-up data. The impact of patient-specific factors on the rate of perfusion defects was assessed at various time points using univariate and multivariate analysis. The impact of set-up errors on the rate of perfusion defects was also analyzed using a one-tailed Fisher’s Exact test. Results: Consistent with our prior results, the volume of LV in the RT field was the most significant predictor of perfusion defects on both univariate (p = 0.0005 to 0.0058) and multivariate analysis (p = 0.0026 to 0.0029). Body mass index (BMI) was the only significant patient-specific factor on both univariate (p = 0.0005 to 0.022) and multivariate analysis (p = 0.0091 to 0.05). In patients with very small volumes of LV in the planned RT fields, the rate of perfusion defects was significantly higher when the fields set-up “too deep” (83% vs. 30%, p = 0.059). The frequency of deep set-up errors was significantly higher among patients with BMI ≥25 kg/m2 compared with patients of normal weight (47% vs. 28%, p = 0.068). Conclusions: BMI ≥25 kg/m2 may be a significant risk factor for cardiac toxicity after RT for left-sided breast cancer, possibly because of more frequent deep set-up errors resulting in the inclusion of additional heart in the RT fields. Further study is necessary to better understand the impact of patient-specific factors and set-up errors on the development of RT-induced perfusion defects. [Copyright &y& Elsevier]

Background: Ductal carcinoma in situ with microinvasion (DCISM) represents ~1% of all breast cancer cases and is arguably a more aggressive subtype of ductal carcinoma in situ (DCIS). Lacking studies with a large population, the survival outcomes of DCISM are still poorly understood and the treatment recommendations remain controversial. This study aims to investigate the long‐term outcome of patients with DCISM, potential risk factors for their prognosis, and the difference of survival between patients treated with breast‐conserving surgery plus radiotherapy (BCT + RT) and mastectomy only. Methods: In total, 1299 patients from 2008 to 2019 with DCISM were retrospectively retrieved. Clinicopathological features were analyzed. Subgroup analysis was conducted between patients who underwent BCT + RT and mastectomy only. Univariate and multivariate analyses were performed to identify prognostic factors for survival. Differences of survival between two groups were compared using the log‐rank test. Results: Totally, 1286 patients had follow‐up information, the median follow‐up is 54.57 months, the 5‐year local–regional‐free survival (LRFS), distant metastasis‐free survival (DMFS), and overall survival (OS) were 98.6%, 97.1%, and 99.4%, respectively, two deaths were due to breast cancer. Multivariate analysis identified age <40 (p = 0.028) and close margin (≤2 mm) as independent negative prognostic factors for LRFS. No prognostic factors were identified for DMFS and OS. The 5‐year LRFS, DMFS, and OS of patients who had DCIS component ≥5 cm and underwent mastectomy without adjuvant radiotherapy were 100%, 98.4%, and 98.4%, respectively. After propensity score matching (PSM), no survival difference was observed between patients treated with BCT + RT or mastectomy only. Conclusions: DCISM patients had a good survival, even those with DCIS component ≥5 cm. Patients aged <40 or with close margin (≤2 mm) had a poorer LRFS, but not DMFS or OS. BCT + RT is a feasible choice for DCISM patients. [ABSTRACT FROM AUTHOR]

The purpose of this study was to explore the value of brachytherapy (BT) in metastatic cervical cancer, as it has not been well evaluated before. We analyzed 2391 patients with Stage IVB cervical cancer from 2004 to 2015 by using data from the Surveillance, Epidemiology, and End Results registry. The parameters were analyzed by Kaplan–Meier and Cox proportional hazards regression models to evaluate cancer-specific survival (CSS) and overall survival. In general, both univariate and multivariate analysis showed that age, histologic type, tumor size, and chemotherapy were associated with CSS and overall survival (p < 0.05). Further subgroup analysis showed BT alone or BT combined with external beam radiotherapy improved CSS despite the tumor size. In addition, chemotherapy and chemoradiotherapy prolonged CSS compared with external beam radiotherapy alone or no chemotherapy or radiotherapy independently of tumor size (p < 0.05). For newly diagnosed metastatic cervical cancers, BT with or without external beam radiotherapy is associated with improved survival. As an aggressive option, chemoradiotherapy is also a potential treatment strategy. [ABSTRACT FROM AUTHOR]

Recently, the focus of enhancing tumor radiosensitivity has shifted from chemotherapeutics to targeted therapies. Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are a novel class of selective cell cycle therapeutics that target the cyclin D-CDK4/6 complex and induce G1 phase arrest. These agents have demonstrated favorable effects when used as monotherapy or combined with endocrine therapy and targeted inhibitors, stimulating further explorations of other combination strategies. Multiple preclinical studies have indicated that CDK4/6 inhibitors exhibit a synergistic effect with radiotherapy both in vitro and in vivo. The principal mechanisms of radiosensitization effects include inhibition of DNA damage repair, enhancement of apoptosis, and blockade of cell cycle progression, which provide the rationale for clinical use. CDK4/6 inhibitors also induce cellular senescence and promote anti-tumor immunity, which might represent potential mechanisms for radiosensitization. Several small sample clinical studies have preliminarily indicated that the combination of CDK4/6 inhibitors and radiotherapy exhibited well-tolerated toxicity and promising efficacy. However, most clinical trials in combined therapy remain in the recruitment stage. Further work is required to seek optimal radiotherapy-drug combinations. In this review, we describe the effects and underlying mechanisms of CDK4/6 inhibitors as a radiosensitizer and discuss previous clinical studies to evaluate the prospects and challenges of this combination. [ABSTRACT FROM AUTHOR]

Aim: To investigate the impact of biological subtypes in locoregional recurrence in Chinese breast cancer patients receiving postmastectomy radiotherapy (PMRT). Methods and Materials: About 583 patients who received postmastectomy radiation between 2010 and 2012 were retrospectively analyzed. According to immunohistochemical staining profile, patients were classified into: Luminal A‐like, Luminal B‐like, HER2‐positive, and triple‐negative breast cancer (TNBC). Local and regional recurrence (LRR) cumulative incidences were calculated by competing risks methodology and the power of prognostic factors was examined by Gray's test and the test of Fine and Gray. Results: The median follow‐up was 70.9 months. About 34 LRR events occurred. For Luminal A, Luminal B, HER2‐positive, and TNBC patients, the 5‐year LRR cumulative incidence rates were 1.57%, 4.09%, 10.74%, and 10.28%. Compared with Luminal A, HER2‐positive subtype and TNBC had a significant increased risk of LRR (HR was 5.034 and 5.188, respectively). In univariate analysis, predictive factors for higher LRR were HER2‐positive subtype (HR = 4.43, P <.05), TNBC (HR = 4.70, P <.05), and pN3 (HR = 5.83, P <.05). In the multivariate model, HER2‐positive subtype (HR = 5.034, P <.05), TNBC (HR = 5.188, P <.05), and pN3 (HR = 9.607, P <.01) were independent predictors of LRR. LRR without trastuzumab was similar to that of TNBC (without vs TNBC, 17.88% vs 10.28%, P >.05) in HER2‐positive subtype patients, while LRR with trastuzumab was approximate to Luminal A (with vs Luminal A, P >.05). Additionally, endocrine therapy also significantly reduced LRR incidence in the luminal subtype cohort (without vs with therapy, 6.25% vs 2.89%, HR = 0.365, P <.1). Conclusions: Biological subtype was a prognostic factor of LRR in the PMRT setting among Chinese breast cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: The indication for internal mammary node irradiation (IMNI) after preoperative systemic therapy in breast cancer remains vague. This study was designed to evaluate the effect of IMNI in patients with clinical stage II-III breast cancer after preoperative systemic therapy and surgery.Methods and Materials: Between August 2005 and December 2013, 497 patients with clinical stage II-III breast cancer underwent anthracycline- or taxane-based preoperative systemic therapy, surgery, and postoperative radiation therapy. A median dose of 50 Gy (range, 46-60 Gy) in 25 fractions was delivered to the chest wall or breast with IMNI (n = 236) or without IMNI (n = 261). Disease-free survival (DFS) and overall survival (OS) rates with or without IMNI were evaluated using the Kaplan-Meier method and compared with the log-rank test. Propensity score matching was performed to adjust for the unbalanced characteristics between the 2 groups. Prognostic factors associated with survival were evaluated by univariate and multivariate analysis.Results: The median follow-up time was 64 months. Patients with IMNI presented with more advanced clinical T stage, pathologic N stage, positive lymph-vascular invasion, and medically or centrally located disease (P < .05). The 5-year DFS and OS rates were 73.7% and 86.3% in the IMNI group and 71.5% and 86.7% in the non-IMNI group, respectively (P > .05). Multivariate analysis demonstrated that IMNI was an independent prognostic factor for DFS (P = .018) and resulted in a borderline improvement in OS (P = .067). After propensity score matching, characteristics were well balanced. The 5-year DFS rates of IMNI and non-IMNI group were 76.8% and 63.4%, respectively (P = .030), and the 5-year OS rates were 88.9% and 84.1%, respectively (P = .083). IMNI was independently prognostic for DFS (P = .014) and OS (P = .047) in matched patients.Conclusions: IMNI improves survival outcomes in patients with clinical stage II-III breast cancer after preoperative systemic therapy. Further prospective studies are warranted to identify the role of IMNI in the preoperative systemic therapy setting. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess the feasibility of split course radiotherapy (SCRT) and reports long-term outcomes in patients with desmoid tumors (DT). Patients and methods: Between 2001 and 2004, 31 patients with recurrent (n=19) or primary large desmoid fibromatosis (≥10 cm) (n=12) who were treated with SCRT were retrospectively analyzed. All patients were treated with two phases of radiotherapy with a median interval time of 99 days (range: 81–122 days) and a median total dose of 6,399 cGy (range: 5,013–7,039 cGy). The median dose for the first phase was 3,969 cGy/22 Fx (range: 2,999–4,305 cGy), and 2,495 cGy/14 Fx (range: 1,982–3,039 cGy) for the second phase. Progression-free survival (PFS) in response to radiotherapy was evaluated using the Kaplan–Meier method and compared using the log-rank test. The prognostic factors associated with survival were evaluated by univariate and multivariate analyses. Results: The median age of all patients was 30 years (range, 7–58 years). With a median follow-up of 60.4 months (range, 2–187 months), eight patients experienced disease progression after treatment. The PFS rate at 3 and 5 years for the whole population was 90% and 71.3%, respectively. PFS for patients with split course of <100 days or ≥100 days interval was 100% vs 78.6% at 3 years, and 80.4% vs 62.9% at 5 years, respectively (P=0.189). In multivariate analysis, the radiotherapy (RT) interval time was an independent prognostic factor for PFS (≥100 days vs >100 days, HR 11.544, 95% CI 1.034–128.878, P=0.047). PFS was not significantly influenced by age, gender, surgery, tumor location, RT technology, or RT dose. Radiation-related acute complications occurred in nine (29%) patients after RT, and RT-related long-term complications occurred in three (9.7%) patients. Conclusion: SCRT with an appropriate treatment interval (<100 days) is well tolerated byDT patients with favorable long-term outcomes. [ABSTRACT FROM AUTHOR]

Background: To examine the effects of recombinant human endostatin combined with radiotherapy on colorectal cancer HCT-116 cell xenografts in nude mice.Methods: Forty male BALB/c nude mice were injected with human colorectal cancer HCT-116 cells to form xenografts and then randomized into the following 4 groups (each group comprised ten mice): a control group, an endostatin group (20 mg/kg endostatin once a day for 10 days), a radiotherapy group (a 6-Gy dose was administered via a 6-MV X-ray on day 5 post-inoculation), and a combination therapy group (radiotherapy with endostatin treatment). The tumor growth inhibition rate were detected. CD31, vascular endothelial growth factor (VEGF), and hypoxia inducible factor-1α (HIF-1α) expression and microvascular density (MVD) were evaluated by immunohistochemistry. The expression of VEGF protein was also detected by western blotting.Results: The tumor growth inhibition rate in the radiotherapy with endostatin treatment group was significantly higher than those in endostatin group or radiotherapy group (77.67% vs 12.31% and 38.59%; n = 8 per group, P < 0.05). The results of immunohistochemistry showed that treatment with radiotherapy induced significant increases in CD31, VEGF, and HIF-1α expression and MVD compared with treatment with saline, while treatment with endostatin or radiotherapy with endostatin induced reductions in CD31, VEGF, and HIF-1α expression and MVD compared with treatment with saline (n = 8 per group, P < 0.05). The results of western blotting showed that VEGF protein expression in radiotherapy group was significantly increased compared with that in the control group. However, VEGF protein expression in the endostatin or radiotherapy with endostatin groups was significantly decreased compared with that in the control group (n = 8 per group, P < 0.05).Conclusions: Endostatin combined with radiotherapy can significantly inhibit HCT-116 cell xenograft growth, possibly by inhibiting angiogenesis and attenuating tumor cell hypoxia. [ABSTRACT FROM AUTHOR]

Background: Knowledge-based planning (KBP) is a promising technique that can improve plan quality and increase planning efficiency. However, no attempts have been made to extend the domain of KBP for planners with different planning experiences so far. The purpose of this study was to quantify the potential gains for planners with different planning experiences after implementing KBP in intensity modulated radiation therapy (IMRT) plans for left-sided breast cancer patients.Methods: The model libraries were populated with 80 expert clinical plans from treated patients who previously received left-sided breast-conserving surgery and IMRT with simultaneously integrated boost. The libraries were created on the RapidPlanTM. 6 planners with different planning experiences (2 beginner planners, 2 junior planners and 2 senior planners) generated manual and KBP optimized plans for additional 10 patients, similar to those included in the model libraries. The plan qualities were compared between manual and KBP plans.Results: All plans were capable of achieving the prescription requirement. There were almost no statistically significant differences in terms of the planning target volume (PTV) coverage and dose conformality. It was demonstrated that the doses for most of organs-at-risk (OARs) were on average lower or equal in KBP plans compared to manual plans except for the senior planners, where the very small differences were not statistically significant. KBP data showed a systematic trend to have superior dose sparing at most parameters for the heart and ipsilateral lung. The observed decrease in the doses to these OARs could be achieved, particularly for the beginner and junior planners. Many differences were statistically significant.Conclusions: It is feasible to generate acceptable IMRT plans after implementing KBP for left-sided breast cancer. KBP helps to effectively improve the quality of IMRT plans against the benchmark of manual plans for less experienced planners without any manual intervention. KBP showed promise for homogenizing the plan quality by transferring planning expertise from more experienced to less experienced planners. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: To measure the distance between surgical clips and edge of CT-defined seroma in a coronal plane in women who have undergone wide local excision of breast cancer and to evaluate dosimetric coverage of CT-defined boost volumes by conventional clip-based electron fields. Materials and methods: Planning CT images of 30 lumpectomy cavities from 30 patients were reviewed. All seroma cavities had at least 4 clips and Cavity Visualization Score ⩾3. Distances between clips and seroma edge (D c–s) were measured at the radial margins for each patient. Clips-based electron fields were generated by including all the clips with 2cm margin in the coronal plane and three-dimensional conformal radiotherapy plans (3D-CRT) were devised based on CT tumor beds (CT-TBs). The parameters of dose–volume histogram between the two boost treatment plans were analyzed. Results: The mean seroma edge extended beyond the clips by 0.3–0.5cm. In all 120 D c–ss, 76.7% were ⩽0.5cm, 8.3% were >1cm and 15% were between 0.5 and 1cm. Twenty patients (20/30) had D c–smax (The maximal D c–s of each patient)>0.5cm and 7 patients had D c–smax >1cm. With the electron fields, only 46.7% (14/30) had D 90 (The minimal dose received by 90% of the planning target volume (PTV))>90% and geographical miss (any portion of the PTV receiving <50% of the prescribed dose) was found in 36.7% (11/30). D c–smax >0.5cm was associated with D 90 <90% (P <0.001) and >1cm was associated with geographic miss (P =0.001). Conclusions: Surgical clips are not always consistent with the edge of seroma. Electron boost field based on clips leads to insufficient dose coverage to the CT-TB. 3D-CRT planning should be considered to ameliorate the dose coverage to the tumor bed. [Copyright &y& Elsevier]

Purpose: To assess the 6-minute walk test (6MWT) as a predictor of radiation therapy–induced lung injury (RTLI). Methods and Materials: The 6MWT is a simple, economical, and reproducible test that measures both how far a person can walk in 6 min and any associated changes in vital signs. As part of a prospective trial to study RTLI, a pre-RT 6MWT was performed in 41 patients. The predictive capacities of pre-RT 6MWT, forced expiratory volume in 1 s (FEV1), and single-breath diffusing capacity for carbon monoxide (DLCO) for the development of RTLI were assessed with receiver operating curve (ROC) techniques. To evaluate the 6MWT, alone or with mean lung dose (MLD) of radiation, as a predictor of RTLI, the rates of RTLI in patient subgroups defined by 6MWT results were compared by using Fisher’s exact test. Results: Thirty-one patients with ≥3 months’ follow-up were evaluable. The median baseline 6MWT result was 1400 ft. Of 31 patients, 7 developed Grade ≥2 RTLI. Of 15 patients with an MLD >18 Gy (the median), 5 developed RTLI, compared with 2 of 16 with MLD ≤18 Gy (p = 0.22). Among those with an MLD ≤18 Gy, the RTLI rates were 0 of 8 and 2 of 8 for 6MWT results ≥1400 ft or &#60;1400 ft, respectively, p = 0.46. The ROC area under the curve for individual metrics was as follows: FEV1 0.66, MLD 0.70, DLCO 0.61, and 6MWT 0.47. Combining FEV1 with 6MWT increased the ROC to 0.71, suggesting that the ratio might be a better predictor than the individual values. Patients with a high 6MWT/FEV1 ratio had a lower rate of RTLI than those with a relatively low ratio. Conclusions: The 6MWT might provide prognostic information beyond pulmonary function tests and dosimetric parameters in predicting RTLI. Additional work is needed to better assess the utility of these functional metrics. [Copyright &y& Elsevier]

Purpose: To evaluate the clinical and three-dimensional dosimetric parameters associated with esophageal injury after radiotherapy (RT) for non–small-cell lung cancer. Methods and materials: The records of 254 patients treated for non–small-cell lung cancer between 1992 and 2001 were reviewed. A variety of metrics describing the esophageal dose were extracted. The Radiation Therapy Oncology Group toxicity criteria for grading of esophageal injury were used. The median follow-up time for all patients was 43 months (range, 0.5–120 months). Logistic regression analysis, contingency table analyses, and Fisher''s exact tests were used for statistical analysis. Results: Acute toxicity occurred in 199 (78%) of 254 patients. For acute toxicity of Grade 2 or worse, twice-daily RT, age, nodal stage of N2 or worse, and most dosimetric parameters were predictive. Late toxicity occurred in 17 (7%) of 238 patients. The median and maximal time to the onset of late toxicity was 5 and 40 months after RT, respectively. Late toxicity occurred in 2%, 3%, 17%, 26%, and 100% of patients with acute Grade 0, 1, 2, 3, and 4 toxicity, respectively. For late toxicity, the severity of acute toxicity was most predictive. Conclusion: A variety of dosimetric parameters are predictive of acute and late esophageal injury. A strong correlation between the dosimetric parameters prevented a comparison between the predictive abilities of these metrics. The presence of acute injury was the most predictive factor for the development of late injury. Additional studies to define better the predictors of RT-induced esophageal injury are needed. [Copyright &y& Elsevier]