Proton therapy for the treatment of children with CNS malignancies.

Proton therapy is a novel technique for treating pediatric malignancies. As a tool to reduce normal-tissue dose, it has the potential to decrease late toxicity. Although proton therapy has been used for over five decades, most pediatric dosimetry studies and clinical series have been published over the last 10 years. The purpose of this article is to review the physical, radiobiological and economic rationales for proton therapy in pediatric CNS malignancies, and provide an overview of the current challenges and future direction of research and utilization of this approach.

Impact of radiation treatment parameters and adjuvant systemic therapy on cosmetic outcomes after accelerated partial breast irradiation using 3-dimensional conformal radiation therapy technique.

PURPOSE: There are concerns regarding cosmetic outcomes of 3-dimensional conformal accelerated partial breast radiation therapy (3DCRT APBI). Associations between cosmetic outcomes and treatment parameters or receipt of adjuvant systemic therapy were sought to guide 3DCRT APBI. METHODS AND MATERIALS: An analysis of cosmetic outcomes among patients treated with 3DCRT APBI at Moffitt Cancer Center was performed. Overall cosmesis was evaluated using modified Harvard criteria and toxicity outcomes were graded using National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0. Patients were treated to 38.5 Gy in 3.85 Gy twice daily fractions per dose-volume objectives specified in the National Surgical Adjuvant Breast and Bowel B-39/Radiation Therapy Oncology Group 0413 (NSABP B-39/RTOG 0413) trial. RESULTS: At least 1 evaluation was available for 97 treated breasts (94 women) with median follow-up of 17.2 months (range, 1-60 months). Most breasts (90.7%) had grade 1 to 2 (excellent to good) overall cosmesis. Nine breasts (9.3%) had grade 3 to 4 (fair to poor) overall cosmesis, secondary to >25% asymmetry in 5 patients, grade 3 fibrosis in 3 patients, and fat necrosis in 1 patient. Increasing percentage of ipsilateral breast volume receiving more than 50% of the prescription dose (V50%) correlated with less than excellent cosmesis (P < .001), with a threshold V50% of 40%. Telangiectasia formation (6%) correlated with increased evaluation planning target volume (P = .006) and V50% (P = .017). Grade 2+ fibrosis (18%) and grade 1+ induration (83%) were also correlated with increasing V50% (P = .006 and .002, respectively). Smaller ipsilateral breast volume correlated with worsening cosmesis (P = .048) and induration (P = .028). Two of 4 patients receiving chemotherapy developed grade 3 fibrosis (P = .004) and fair/poor cosmesis (P = .04). CONCLUSIONS: The current analysis implies that acceptable cosmetic results are achievable with 3DCRT APBI technique by adhering to optimal radiation therapy dose-volume constraints, particularly ipsilateral breast V50%.

Comparison of daily versus nondaily image-guided radiotherapy protocols for patients treated with intensity-modulated radiotherapy for head and neck cancer.

BACKGROUND: The purpose of this study was to determine the feasibility of nondaily image-guided radiotherapy (RT) strategies with intensity-modulated radiotherapy (IMRT) for head and neck cancer. METHODS: Alignment data was analyzed from 103 consecutive patients treated by IMRT for head and neck cancer who had undergone daily imaging with onboard mega-voltage CT (MVCT), resulting in 3275 images. Geometric setup errors that would have occurred using less-than-daily imaging were hypothetically estimated for 4 temporal less-than-daily image-guided RT protocols. RESULTS: For image-guided RT on the first fraction, weekly image-guided RT, first 5 + weekly image-guided RT, and alternating day image-guided RT, the respective incidences of geometric miss were 50.5%, 33.8%, 30.1%, and 15.7% assuming 3-mm uncertainty margins; and 18.7%, 11.7%, 10.3%, and 4.1% with 5-mm margins. CONCLUSION: Less-than-daily image-guided RT strategies result in a high incidence of potential miss when 3-mm uncertainty margins are utilized. Less-than-daily image-guided RT strategies should incorporate margins of at least 5 mm.

Correlation of radiation treatment interruptions with psychiatric disease and performance status in head and neck cancer patients.

PURPOSE: The purpose of this study is to identify factors predictive of treatment interruptions during radiation therapy (RT) for head and neck cancer. METHODS AND MATERIALS: The medical records of 280 consecutive patients who completed a 6- or 7-week course of RT for squamous cell carcinoma of the head and neck were reviewed. The number of missed treatment days, excluding those due to holidays or machine downtime, was determined for each patient. All patients were treated to a median dose of 63 Gy (range, 60 to 70 Gy). RESULTS: The proportion of patients who missed 0, 3-5, 6-10, and greater than 10 days was 25, 59, 12, and 5 %, respectively. The percentage of patients who missed greater than 5 days was 62 % among the 39 patients with Karnofsky Performance Status (KPS) score of 70 or less compared to 10 % among those with a KPS score of greater than 70 (p < 0.01). Among the 33 patients identified with a preexisting psychiatric condition, the percentage that subsequently missed greater than 5 days of treatment was 48 % compared to 13 % among those without a psychiatric condition. When missed RT days were analyzed as a continuous variable, the correlations with both KPS and preexisting psychiatric condition remained highly significant (p < 0.01, for both). CONCLUSION: Poor performance status and preexisting psychiatric condition predicted for treatment interruptions during RT for head and neck cancer. In view of the possible detrimental effect on treatment outcome, appropriate social programs should be initiated to overcome potential barriers to RT for these particular populations.

Tobacco smoking during radiation therapy for head-and-neck cancer is associated with unfavorable outcome.

PURPOSE: To evaluate the effect of continued cigarette smoking among patients undergoing radiation therapy for head-and-neck cancer by comparing the clinical outcomes among active smokers and quitters. METHODS AND MATERIALS: A review of medical records identified 101 patients with newly diagnosed squamous cell carcinoma of the head and neck who continued to smoke during radiation therapy. Each active smoker was matched to a control patient who had quit smoking before initiation of radiation therapy. Matching was based on tobacco history (pack-years), primary site, age, sex, Karnofsky Performance Status, disease stage, radiation dose, chemotherapy use, year of treatment, and whether surgical resection was performed. Outcomes were compared by use of Kaplan-Meier analysis. Normal tissue effects were graded according to the Radiation Therapy Oncology Group/European Organization for the Treatment of Cancer toxicity criteria. RESULTS: With a median follow-up of 49 months, active smokers had significantly inferior 5-year overall survival (23% vs. 55%), locoregional control (58% vs. 69%), and disease-free survival (42% vs. 65%) compared with the former smokers who had quit before radiation therapy (p < 0.05 for all). These differences remained statistically significant when patients treated by postoperative or definitive radiation therapy were analyzed separately. The incidence of Grade 3 or greater late complications was also significantly increased among active smokers compared with former smokers (49% vs. 31%, p = 0.01). CONCLUSIONS: Tobacco smoking during radiation therapy for head-and-neck cancer is associated with unfavorable outcomes. Further studies analyzing the biologic and molecular reasons underlying these differences are planned.

Potential of helical tomotherapy to reduce dose to the ocular structures for patients treated for unresectable sinonasal cancer.

PURPOSE: To compare intensity-modulated radiotherapy (IMRT) treatment plans generated by segmental multileaf collimator (SMLC) and helical tomotherapy (HT) techniques for patients with unresectable sinonasal cancer. METHODS AND MATERIALS: SMLC-IMRT and HT-IMRT plans for 5 patients with cancer of the paranasal sinuses and nasal cavity were independently optimized using the Eclipse treatment planning system (Varian Medial Systems, Palo Alto, CA) and Tomotherapy HI-ART treatment planning system (Tomotherapy, Inc, Madison, WI). The goal was to deliver a prescribed dose of 70 Gy to at least 95% of the planning target volume (PTV) encompassing gross tumor over 35 treatments whereas respecting constraints to organs at risk, notably the ocular structures. RESULTS: HT-IMRT reduced the maximum doses to the optic chiasm, as well as to the ipsilateral optic nerve and retina (P < 0.05, for all). Maximum doses to these structures were reduced by 10%, 16%, and 14%, respectively, using HT-IMRT compared with SMLC-IMRT. Additionally, the mean dose to the ipsilateral lacrimal gland was reduced by 32% using HT-IMRT. With respect to conformality, HT-IMRT improved dose homogeneity by decreasing "hot-spots." The mean percentage of PTV70 receiving greater than 77 Gy (110% of the prescribed dose) was 4.0% for the HT-IMRT plans compared with 17.8% for the SMLC-IMRT plans (P = 0.001). CONCLUSIONS: HT-IMRT has the potential to improve dose homogeneity to PTVs whereas reducing dose to the optic structures. Clinical implications are discussed.

Initial clinical experience with helical tomotherapy for head and neck cancer.

BACKGROUND: To report a single-institutional experience with the use of helical tomotherapy (HT)-based intensity-modulated radiotherapy (IMRT) for head and neck cancer. METHODS: Seventy-seven consecutive patients were treated with HT for squamous cell carcinoma of the head and neck to a median dose of 66 Gy (range, 60 to 72 Gy). Megavoltage CT scans were obtained as part of an image-guided registration protocol for patient alignment before each treatment. Concurrent chemotherapy was administered to 48 patients (62%). RESULTS: The 2-year estimates of overall survival, local-regional control, and disease-free survival were 82%, 77%, and 71%, respectively. Spatial evaluation of local-regional failures revealed that 16 of the 18 patients who progressed in the primary site or neck failed in the high-dose planning target volume (PTV). CONCLUSIONS: HT appears to achieve clinical outcomes comparable to contemporary series reporting on IMRT for head and neck cancer.