Adaptive radiotherapy for head and neck cancer--dosimetric results from a prospective clinical trial.

PURPOSE: To conduct a clinical trial evaluating adaptive head and neck radiotherapy (ART). METHODS: Patients with locally advanced oropharyngeal cancer were prospectively enrolled. Daily CT-guided setup and deformable image registration permitted mapping of dose to avoidance structures and CTVs. We compared four planning scenarios: (1) original IMRT plan aligned daily to marked isocenter (BB); (2) original plan aligned daily to bone (IGRT); (3) IGRT with one adaptive replan (ART1); and (4) actual treatment received by each study patient (IGRT with one or two adaptive replans, ART2). RESULTS: All 22 study patients underwent one replan (ART1); eight patients had two replans (ART2). ART1 reduced mean dose to contralateral parotid by 0.6 Gy or 2.8% (paired t-test; p=0.003) and ipsilateral parotid by 1.3 Gy (3.9%) (p=0.002) over the IGRT alone. ART2 further reduced the mean contralateral parotid dose by 0.8 Gy or 3.8% (p=0.026) and ipsilateral parotid by 4.1 Gy or 9% (p=0.001). ART significantly reduced integral body dose. CONCLUSIONS: This pilot trial suggests that head and neck ART dosimetrically outperforms IMRT. IGRT that leverages conventional PTV margins does not improve dosimetry. One properly timed replan delivers the majority of achievable dosimetric improvement. The clinical impact of ART must be confirmed by future trials.

Evaluating the impact of patient, tumor, and treatment characteristics on the development of jaw complications in patients treated for oral cancers: a SEER-Medicare analysis.

BACKGROUND: Jaw complications, including osteoradionecrosis, are significant sequelae of radiation therapy (RT) for oral cancers. This study identifies the impact of patient, tumor, and treatment characteristics on the development of jaw complications in patients treated with RT. METHODS: The Surveillance, Epidemiology, and End Results (SEER)-Medicare database was used to identify patients treated with RT for oral cancers from 1999 to 2007. Jaw complications were identified by International Classification of Diseases 9th revision (ICD-9) diagnosis codes and/or related procedures using Current Procedural Terminology (CPT) and ICD-9 codes. RESULTS: A total of 1848 patients were identified. With a median follow-up of 2.5 years, 297 patients (16.1%) developed jaw complications: 226 patients had a diagnosis, 41 patients had a procedure, and 30 patients had both. On multivariate analysis, female sex, lack of chemotherapy use, and fewer comorbidities were associated with a statistically significant increase in jaw complications. CONCLUSIONS: Even with modern techniques, jaw complications are a notable and potentially devastating side effect of RT for oral cancers.

Impact of gender, partner status, and race on locoregional failure and overall survival in head and neck cancer patients in three radiation therapy oncology group trials.

PURPOSE: We investigated the impact of race, in conjunction with gender and partner status, on locoregional control (LRC) and overall survival (OS) in three head and neck trials conducted by the Radiation Therapy Oncology Group (RTOG). METHODS AND MATERIALS: Patients from RTOG studies 9003, 9111, and 9703 were included. Patients were stratified by treatment arms. Covariates of interest were partner status (partnered vs. non-partnered), race (white vs. non-white), and sex (female vs. male). Chi-square testing demonstrated homogeneity across treatment arms. Hazards ratio (HR) was used to estimate time to event outcome. Unadjusted and adjusted HRs were calculated for all covariates with associated 95% confidence intervals (CIs) and p values. RESULTS: A total of 1,736 patients were analyzed. Unpartnered males had inferior OS rates compared to partnered females (adjusted HR = 1.22, 95% CI, 1.09-1.36), partnered males (adjusted HR = 1.20, 95% CI, 1.09-1.28), and unpartnered females (adjusted HR = 1.20, 95% CI, 1.09-1.32). White females had superior OS compared with white males, non-white females, and non-white males. Non-white males had inferior OS compared to white males. Partnered whites had improved OS relative to partnered non-white, unpartnered white, and unpartnered non-white patients. Unpartnered males had inferior LRC compared to partnered males (adjusted HR = 1.26, 95% CI, 1.09-1.46) and unpartnered females (adjusted HR = 1.30, 95% CI, 1.05-1.62). White females had LRC superior to non-white males and females. White males had improved LRC compared to non-white males. Partnered whites had improved LRC compared to partnered and unpartnered non-white patients. Unpartnered whites had improved LRC compared to unpartnered non-whites. CONCLUSIONS: Race, gender, and partner status had impacts on both OS and locoregional failure, both singly and in combination.

Evaluation of insulin-like growth factor-1 for prevention of radiation-induced spinal cord damage.

AIM: To test whether insulin-like growth factor-1 (IGF-1) ameliorates radiation-induced spinal cord myelopathy and to establish the dose-effect relationship for this growth factor which has not been administered in conjunction with spinal cord irradiation to date. METHODS: Animal experiments were conducted to test the feasibility of IGF-1 injection in a model of cervical spinal cord irradiation in adult Fisher F-344 rats and to determine the most effective dose level of IGF-1. Irradiation was given in two fractions (16 Gy followed by 18 Gy) and animals were examined for the development of paresis (follow-up 12 months). RESULTS: The dose-finding experiment revealed significant differences in the incidence of radiation myelopathy (RM). The most effective dose of IGF-1 was 50 microg per day. CONCLUSIONS: IGF-1 showed promising activity as a radioprotective agent in a model of high-dose spinal cord irradiation. Further studies are needed to examine the results with multiple small doses of radiation as widely applied in clinical protocols.

Effect of education level on outcome of patients treated on Radiation Therapy Oncology Group Protocol 90-03.

BACKGROUND: It has been hypothesized that people in lower socioeconomic groups have worse outcomes because they present with advanced-stage cancers or receive inadequate treatment. The authors investigated this hypothesis by using education level as a proxy for socioeconomic status in patients treated on Radiation Therapy Oncology Group (RTOG) Protocol 90-03. METHODS: RTOG 90-03 was a Phase III randomized trial investigating four different radiation fractionation schedules in the treatment of locally advanced head and neck carcinomas. Overall survival and locoregional control rates were analyzed by education level as measured by patient response on the demographic form at study entry. RESULTS: A significant difference was observed in the distribution of patients by education level between the standard fractionated radiation treatment arm and the hyperfractionated radiation treatment arm. More patients in the standard fractionated treatment arm had a higher education level (P = 0.018). Patients attending college had highly and significantly better overall survival and locoregional control than the other groups combined (P = 0.0056 and P = 0.025, respectively: from Cox proportional hazards models stratified by assigned treatment with educational level, T classification, N classification, Karnofsky performance status, primary site, and race). Multivariate analysis revealed that education level was significant for predicting both overall survival and locoregional control when comparing attended college/technical school compared with all other education levels. CONCLUSIONS: Patients attending college or technical school had improved overall survival and locoregional control. These differences cannot be explained by differences in tumor stage or treatment. Poorer overall health or lack of support systems contributing to these results needs to be investigated further.

Adjuvant irradiation for cervical lymph node metastases from melanoma.

BACKGROUND: The risk of regional disease recurrence after surgery alone for lymph node metastases from melanoma is well documented. The role of adjuvant irradiation remains controversial. METHODS: The medical records of 160 patients with cervical lymph node metastases from melanoma were reviewed retrospectively. Of these, 148 (93%) presented with clinically palpable lymph node metastases. All patients underwent surgery and radiation to a median dose of 30 grays (Gy) at 6 Gy per fraction delivered twice weekly. Surgical resection was either a selective neck dissection in 90 patients or local excision of the lymph node metastasis in 35 patients. Only 35 patients underwent a radical, modified radical, or functional neck dissection. RESULTS: At a median follow-up of 78 months, the actuarial local, regional, and locoregional control rates at 10 years were 94%, 94%, and 91%, respectively. Univariate analysis of patient, tumor, and treatment characteristics failed to reveal any association with the subsequent rate of local or regional control. The actuarial disease-specific (DSS), disease-free, and distant metastasis-free survival (DMFS) rates at 10 years were 48%, 42%, and 43%, respectively. Univariate and multivariate analyses revealed that patients with four or more involved lymph nodes had a significantly worse DSS and DMFS. Nine patients developed a treatment-related complication requiring medical management, resulting in a 5-year actuarial complication-free survival rate of 90%. CONCLUSIONS: Adjuvant radiotherapy resulted in a 10-year regional control rate of 94%. Complications for all patients were rare and manageable when they did occur. The authors recommend adjuvant irradiation for patients with extracapsular extension, lymph nodes measuring 3 cm in size or larger, the involvement of multiple lymph nodes, recurrent disease, or any patient having undergone a selective therapeutic neck dissection.