Late Toxicities of Intensity-Modulated Radiation Therapy for Head and Neck Rhabdomyosarcoma.

PURPOSE/OBJECTIVES: To examine the late effects of intensity-modulated radiation therapy (IMRT) in pediatric patients with rhabdomyosarcoma of the head and neck. MATERIALS/METHODS: All 1-year survivors of pediatric head and neck rhabdomyosarcoma treated with IMRT at a single institution from 1999 to 2014 were assessed for long-term complications. Late toxicities were graded according to CTCAE version 4.03. RESULTS: Among 30 patients, median age at IMRT was 7.4 (1.5-20.8) years, median follow-up was 7.7 (1.2-14.4) years, and median IMRT dose was 50.4 (36-50.4) Gy. Tumor subsites included parameningeal (80%), orbit (13%), and other (7%). Common late toxicities were facial disfigurement (n = 23, 77%), growth hormone deficiency (n = 11, 37%), cataract (n = 10, 34%), and dental problems (n = 10, 33%). Twenty-two patients (73%) had ≥2 late toxicities and 14 patients (47%) had ≥3 late toxicities. Seventeen patients (57%) experienced grade 2 toxicity and 10 patients (33%) had grade 3 toxicity. Grade 3 toxicities included visual disturbance, cataract, facial disfigurement, chronic sinusitis/otitis, and hearing loss. Severe facial deformity was noted in nine patients (30%), and three patients underwent cosmetic surgery. Patients with severe facial deformity were treated at younger ages (median 6.0 years vs. 8.1 years for patients with no/nonsevere facial deformity) and more likely to have infratemporal fossa tumors. There were no secondary solid malignancies. CONCLUSIONS: Late radiation toxicities are common in survivors of pediatric head and neck rhabdomyosarcoma treated with IMRT. While the majority of late effects are mild-moderate, they can significantly impact quality of life, particularly facial disfigurement.

Long-term effect of chemotherapy-intensity-modulated radiation therapy (chemo-IMRT) on dentofacial development in head and neck rhabdomyosarcoma patients.

Dentofacial developmental abnormalities have been reported in head and neck rhabdomyosarcoma (HNRMS) patients treated with conventional radiotherapy technique and chemotherapy. This current study investigates dentofacial long-term effects among HNRMS survivors managed with intensity-modulated radiotherapy (IMRT) and chemotherapy. In general, IMRT is a more effective 3D-conformal radiotherapy technique, which delivers high doses of radiation to the tumor target while minimizing doses received by the surrounding normal tissues. The medical records and radiographs of thirteen patients were reviewed to identify the following: 1. Facial asymmetry and jaw hypoplasia. 2. Effects on the dental tissue causing tooth agenesis/hypodontia, root agenesis/stunting/malformation, and/or enamel hypoplasia. 3. Trismus, hyposalivation/xerostomia. Seven patients presented with facial asymmetry and jaw hypoplasia, 9 patients presented with effects on the dental tissue [root agenesis/stunting/malformation (9), tooth agenesis/hypodontia (7) and enamel hypoplasia (3)] and 7 patients developed trismus and /or xerostomia. All patients with facial asymmetry and jaw hypoplasia also developed dental abnormalities. Patients with dentofacial developmental abnormalities were ≤7 years of age at treatment. Our study shows that dentofacial developmental abnormalities are still a burden in the era of IMRT and as prognosis of childhood malignancy improves and more patients survive, these late dentofacial sequelae among childhood cancer survivors will become more common. Dental oncologists should be integral members in the management of children with head and neck cancers.

Intensive multimodality therapy for patients with stage 4a metastatic retinoblastoma.

BACKGROUND: We previously reported promising pilot results treating patients with stage 4a metastatic retinoblastoma with combined intensive conventional chemotherapy, high-dose chemotherapy with autologous hematopoietic stem cell rescue, and radiation therapy and now present an expanded and updated series. PROCEDURE: Fifteen patients with bone marrow (n = 14), bone (n = 10), orbit (n = 9), and/or liver (n = 4) disease were treated. Induction chemotherapy usually consisted of vincristine, cyclophosphamide, cisplatin, and etoposide. The high-dose chemotherapy regimen included carboplatin and thiotepa alone (n = 1) or with etoposide (n = 5) or topotecan (n = 7). RESULTS: Bone marrow cleared at first post-initiation of chemotherapy examination in all patients and stem cells were harvested after a median of 3.5 cycles of chemotherapy (range 3-6 cycles). Two patients progressed prior to high-dose chemotherapy and died. Thirteen received high-dose chemotherapy at a median of 6 months post-diagnosis of metastases (range 4-8 months). Ten are retinoblastoma-free in first remission at a median follow-up of 103 months (range 34-202 months) while three recurred (two in the CNS, one in the mandible) 14-20 months post-diagnosis of metastases. Retinoblastoma-free and event-free survival at 5 years are 67% (95% confidence interval 38-85%) and 59% (95% confidence interval 31-79%). Six of the 10 survivors received radiation therapy. Three patients developed secondary osteosarcoma 14, 4, and 9 years after diagnosis of metastatic disease. CONCLUSIONS: Intensive multimodality therapy including high-dose chemotherapy with autologous hematopoietic stem cell rescue was curative for the majority of patients with stage 4a metastatic retinoblastoma treated. The contribution of external beam radiation therapy is unclear.

Customized high-dose-rate brachytherapy using MRI planning for vaginal rhabdomyosarcoma.

PURPOSE: To report the technical aspects of customized high-dose-rate brachytherapy for vaginal rhabdomyosarcoma using MRI- and CT-based planning in a 20-month-old girl. METHODS AND MATERIALS: An impression of the vaginal cavity at the resection site was taken after adequate lubrication of the vagina with lidocaine jelly. The impression was processed in the dental laboratory to obtain an MRI-compatible device with three imbedded catheters 0.4 mm apart, assuring tumor coverage. An MRI- and CT-based simulation under anesthesia with the applicator in place were performed, and the images were registered for contouring and planning to deliver 40 Gy in 10 fractions daily. Dose to the ovaries was limited to a mean dose less than 4 Gy. Treatment was delivered daily under anesthesia with no acute complications. RESULTS: Brachytherapy using a customized applicator has many advantages over prefabricated vaginal cylinders for young girls. It allows greater dose distribution conformality with the possibility of contralateral vaginal wall sparing and more reproducible daily positioning. MRI-based planning is mainly performed to facilitate delineation of the target volume and the ovaries, which are easily identified on MRI. CONCLUSIONS: The customized applicator offers many advantages of which treatment reproducibility, inherent MRI compatibility, and excellent dose distribution conformality. Our brachytherapy technique using MRI and CT scan planning allows precise tumor and normal tissues delineation resulting in excellent tumor coverage and normal tissues sparing.

Irradiation for locoregionally recurrent, never-irradiated oral cavity cancers.

BACKGROUND: The purpose of this study was to report the clinical outcomes and related prognostic factors of patients who underwent radiotherapy (RT) for the treatment of recurrent, never-irradiated oral cavity cancer (recurrent OCC). METHODS: The records of consecutive patients with nonmetastatic recurrent OCC who presented to and were treated with RT at our institution between 1989 and 2011 were reviewed. The Kaplan-Meier method was used to calculate overall survival (OS). The cumulative incidences of disease-specific death, local failure, regional failure, and distant metastasis were calculated with death as a competing risk. RESULTS: One hundred twenty-three patients were identified. Median follow-up for living patients was 54 months and 16 months for all patients. Ninety-one patients had salvage surgery followed by adjuvant RT. Definitive RT was utilized in the remaining 32 patients. The 5-year OS was 40%. The 5-year cumulative incidence of disease-specific death, local failure, regional failure, and distant metastasis was 55%, 34%, 22%, and 20%, respectively. Recurrent T classification and lack of salvage surgery were independently associated with worse disease-specific death and decreased OS, respectively. Subset analysis of patients who underwent salvage surgery demonstrated that age, recurrent T classification, and perineural invasion (PNI) were independently associated with decreased OS; recurrent T classification and thicker tumors were independently associated with worse disease-specific death; and positive/close margins and primary T classification were independently associated with increased local failure. CONCLUSION: In this group of patients with recurrent OCC, clinical outcomes were similar or improved when compared with other recurrent OCC-specific reports. In the salvage surgery subset, tumor thickness and PNI are recurrent pathologic features associated with outcomes that were only previously demonstrated in studies of primary disease. Because of the relatively worse outcomes in patients receiving definitive or adjuvant RT for recurrent OCC, we advocate for the appropriate use of postoperative RT in the initial management of oral cavity cancers.

Correlation of osteoradionecrosis and dental events with dosimetric parameters in intensity-modulated radiation therapy for head-and-neck cancer.

PURPOSE: Osteoradionecrosis (ORN) is a known complication of radiation therapy to the head and neck. However, the incidence of this complication with intensity-modulated radiation therapy (IMRT) and dental sequelae with this technique have not been fully elucidated. METHODS AND MATERIALS: From December 2000 to July 2007, 168 patients from our institution have been previously reported for IMRT of the oral cavity, nasopharynx, larynx/hypopharynx, sinus, and oropharynx. All patients underwent pretreatment dental evaluation, including panoramic radiographs, an aggressive fluoride regimen, and a mouthguard when indicated. The median maximum mandibular dose was 6,798 cGy, and the median mean mandibular dose was 3,845 cGy. Patient visits were retrospectively reviewed for the incidence of ORN, and dental records were reviewed for the development of dental events. Univariate analysis was then used to assess the effect of mandibular and parotid gland dosimetric parameters on dental endpoints. RESULTS: With a median clinic follow-up of 37.4 months (range, 0.8-89.6 months), 2 patients, both with oral cavity primaries, experienced ORN. Neither patient had preradiation dental extractions. The maximum mandibular dose and mean mandibular dose of the 2 patients were 7,183 and 6,828 cGy and 5812 and 5335 cGy, respectively. In all, 17% of the patients (n = 29) experienced a dental event. A mean parotid dose of >26 Gy was predictive of a subsequent dental caries, whereas a maximum mandibular dose >70 Gy and a mean mandibular dose >40 Gy were correlated with dental extractions after IMRT. CONCLUSIONS: ORN is rare after head-and-neck IMRT, but is more common with oral cavity primaries. Our results suggest different mechanisms for radiation-induced caries versus extractions.

Intensity-modulated radiotherapy in postoperative treatment of oral cavity cancers.

PURPOSE: To present our single-institution experience of intensity-modulated radiotherapy (IMRT) for oral cavity cancer. METHODS AND MATERIALS: Between September 2000 and December 2006, 35 patients with histologically confirmed squamous cell carcinoma of the oral cavity underwent surgery followed by postoperative IMRT. The sites included were buccal mucosa in 8, oral tongue in 11, floor of the mouth in 9, gingiva in 4, hard palate in 2, and retromolar trigone in 1. Most patients had Stage III-IV disease (80%). Ten patients (29%) also received concurrent postoperative chemotherapy with IMRT. The median prescribed radiation dose was 60 Gy. RESULTS: The median follow-up for surviving patients was 28.1 months (range, 11.9-85.1). Treatment failure occurred in 11 cases as follows: local in 4, regional in 2, and distant metastases in 5. Of the 5 patients with distant metastases, 2 presented with dermal metastases. The 2- and 3-year estimates of locoregional progression-free survival, distant metastasis-free survival, disease-free survival, and overall survival were 84% and 77%, 85% and 85%, 70% and 64%, and 74% and 74%, respectively. Acute Grade 2 or greater dermatitis, mucositis, and esophageal reactions were experienced by 54%, 66%, and 40% of the patients, respectively. Documented late complications included trismus (17%) and osteoradionecrosis (5%). CONCLUSION: IMRT as an adjuvant treatment after surgical resection for oral cavity tumors is feasible and effective, with promising results and acceptable toxicity.

Effects of therapy on dentofacial development in long-term survivors of head and neck rhabdomyosarcoma: the memorial sloan-kettering cancer center experience.

PURPOSE: To describe potential effects of multimodality therapy on dental and facial development in long-term survivors of head and neck rhabdomyosarcoma. PATIENTS AND METHODS: The medical records of all patients aged 20 years or less presenting between 1985 and 1996 with a diagnosis of rhabdomyosarcoma and treated by protocol were reviewed. Head and neck rhabdomyosarcoma patients who were followed in the Dental Service and were alive and free of disease with at least a 5-year follow-up were included in the review. Ten patients satisfied the inclusion criteria and form the basis of this report. The median age at diagnosis of the 10 patients was 4.3 years (range 10 months to 19.5 years). All patients were treated with chemotherapy, two patients underwent surgery, and all but one patient received external beam radiation therapy. RESULTS: Clinical or radiographic dentofacial abnormalities were observed in 8 of the 10 (80%) patients. Abnormalities included enamel defects, bony hypoplasia/facial asymmetry, trismus, velopharyngeal incompetency, tooth/root agenesis, and disturbance in root development. Bony hypoplasia and disturbance in root formation were the most common findings. CONCLUSIONS: Multimodality therapy for head and neck rhabdomyosarcoma can result in dentofacial abnormalities that affect the patient's quality of life. The care of the long-term survivor requires a multidisciplinary approach, including early involvement of the dental team.