Faculty Bibliography

Primary mucosal melanoma of the head and neck (MMHN) comprises approximately 1% of all malignant melanomas. It presents more commonly in an elderly population and has no significant gender predominance. Given its rarity, most evidence of the causes, behavior, and treatment approaches for MMHN originates from isolated case reports and retrospective series. Between 1945 and 2011, at least 1951 cases of MMHN have been reported in the literature. Despite numerous technological developments in surgery and radiation therapy, as well as advances in systemic modalities, MMHN is an aggressive malignancy with a very poor prognosis. Complete surgical excision with clear margins remains the primary treatment modality. Adjuvant postoperative radiation therapy may improve locoregional control but does not appear to affect survival. Definitive particle radiation therapy promises to provide high rates of local control for nonoperable patients. Recent molecular evidence suggests that proto-oncogene KIT aberrations in a subset of mucosal melanomas may represent a potential diagnostic value and serve as a therapeutic target for tyrosine kinase inhibitors in an adjuvant setting for patients with advanced MMHN.

Brachytherapy consists of placing radioactive sources within, or directly adjacent to a tumor, and is a means of delivering highly targeted and conformal radiation. While its history dates back to the origins of the field, in recent years brachytherapy treatment paradigms have been evolving considerably. This has been driven primarily by advancements in imaging, which allow for precise placement of sources and applicators under image guidance, and volume-based optimization to ensure adequate tumor coverage while sparing adjacent normal tissue. There has been a shift towards high-dose-rate (HDR) brachytherapy for many of the disease sites treated with brachytherapy. Simultaneously, with increasingly conformal treatment, there has been a shift towards utilization of higher doses per fraction, over fewer fractions, for specific disease sites where hypofractionation is believed to confer a radiobiological benefit. Here we review recent data and trends for those disease sites and conditions that are commonly treated with brachytherapy, including prostate, gynecologic, breast, head and neck, and skin cancers and salvage of recurrent disease.

In this era of globalization and rapid advances in radiation oncology worldwide, the American Society for Radiation Oncology (ASTRO) is committed to help decrease profound regional disparities through the work of the International Education Subcommittee (IES). The IES has expanded its base, reach, and activities to foster educational advances through a variety of educational methods with broad scope, in addition to committing to the advancement of radiation oncology care for cancer patients around the world, through close collaboration with our sister radiation oncology societies and other educational, governmental, and organizational groups.

Concomitant chemoradiotherapy provides organ preservation for those patients with head and neck cancer. We report the results of a prospective study that examined functional outcomes and quality of life (QOL) after chemoradiotherapy over the first 6 months post-treatment (tx). Twenty-nine patients with head and neck cancer were treated with chemoradiotherapy. All were seen baseline and 3 and 6 months post-tx. Assessments included the performance status scale (PSS), Karnofsky performance status scale, tongue strength, jaw opening, and saliva weight. QOL was patient-rated using the eating assessment tool (EAT-10), MD Anderson dysphagia inventory, speech handicap index (SHI), and the EORTC H&N35 scale. Repeated-measures ANOVAs were used, with significance at p < 0.05. PSS scores were significantly different across time points. Tongue strength, jaw range of motion (ROM), and saliva weight were significantly lower at 3 and 6 months than at baseline. QOL was significantly worse after tx, although it improved by 6 months as rated with the EAT-10 and the SHI scores were significantly worse at 3 and 6 months. EORTC domains of swallowing, senses, speech, dry mouth, and sticky saliva were significantly worse at 3 and 6 months. Concomitant chemoradiotherapy for treatment of head and neck tumors can result in impaired performance outcomes and QOL over the first 6 months post-tx. However, performance status, tongue strength, jaw ROM, and eating QOL were only mildly impaired by 6 months post-tx. Saliva production and speech QOL remained significantly impaired at 6 months post-treatment. Current studies are examining outcomes at 12 and 24 months post-treatment to better predict outcomes over time in this population.

PURPOSE: Perineural invasion (PNI) is a frequent pathological finding in head and neck cancers. When adjuvant radiation to cranial nerves at risk in head and neck cancers with PNI is considered, there is a need for consensus on which nerves are at risk and how to contour these nerves. This contouring guide attempts to address this need. METHODS AND MATERIALS: Representative patient diagnostic computed tomographic (CT) scans with contrast of the neck were used to create example contours. The cranial nerves V2, V3, VII, and XII, and sample primary tumor sites were initially delineated using the Varian Eclipse planning system by 5 radiation oncologists. All of the images were then reviewed with a diagnostic radiologist to establish consensus for delineating the cranial nerves. RESULTS: We provided detailed contouring and planning guidelines on a CT atlas, with figures to help illustrate internerve connections, based on clinical experience, literature-based patterns of failure, and established anatomic connections between cranial nerves. Tumor bed, cranial nerve, and elective target volumes are depicted. CONCLUSIONS: These planning guidelines and atlas provide anatomic, clinical, and technical recommendations for guiding radiation oncologists in the planning and delivery of intensity modulated radiation therapy for head and neck cancer with PNI.

PURPOSE: To retrospectively review our single institution experience of patients with tonsillar squamous cell carcinoma. MATERIAL AND METHODS: Between 1999 and 2005, a total of 79 patients were identified. Stage distribution was as follows: stages I-II, III, IVA, and IVB were in 6, 14, 43, and 16 patients, respectively. Sixty-three patients (80%) were male. Median age was 55.5 years. Treatment generally consisted of external beam radiation therapy (RT) (median dose, 70 Gy), concomitant chemotherapy (CCRT) (cisplatin 100 mg/m on days 1, 22, and 43), and neck dissection (ND), and was administered as follows: stages I/II, 6 patients received RT alone; stages III/IVA, 20, 5, and 32 patients received RT alone, CCRT, and CCRT followed by ND, respectively; stage IVB, 9 and 7 patients received CCRT and CCRT plus ND, respectively. RESULTS: After a median follow-up of 56 months (range, 12 to 122 mo), the 5-year local control (LC), regional control (RC), distant control (DC), and overall survival (OS) by stage were as follows: stage I-II 100%, 100%, 100%, 100%; stage III-IVA 98%, 96%, 95%, and 88%; stage IVB 100%, 100%, 69%, and 66%, respectively. Among stage IVB patients, DC was significantly lower (P=0.01) and a trend toward lower OS was noted (P=0.08). Long-term percutaneous endoscopic gastrostomy dependence was noted in 3% of them who had received CCRT. The effect of both chemotherapy and ND on treatment outcomes was analyzed; in stage III/IVA patients treated with or without chemotherapy, LC was 97% and 100% (P=0.43); RC was 92% and 100%(P=0.27); and DC was 91% and 94% (P=0.92), respectively. In stage III/IVA, patients treated with CCRT with or without ND, RC was 100% and 88%, respectively (P=0.087). CONCLUSIONS: Primary radiotherapy with or without CCRT followed by ND provides excellent tumor control with acceptable toxicity in treating squamous cell carcinoma of the tonsil.

AIM: To evaluate the locoregional control and treatment toxicity of patients with pleomorphic adenoma after resection with close or positive margins followed by postoperative radiation therapy (PORT). PATIENTS AND METHODS: Between 2002 and 2011, twenty-one patients underwent PORT at the Mount Sinai Beth Israel Medical Center for pleomorphic adenoma of the parotid with close or positive margins. Four out of the 21 patients (19%) had recurrent lesions. The median dose was 57.6 Gy (range 55.8-69.96) delivered at 1.8-2.12 Gy/fraction. Treatment and follow-up data were retrospectively analyzed for locoregional control as well as acute- and late-treatment toxicities. Actuarial survival analysis was also performed. RESULTS: Twelve women and 9 men with a median age of 46 (26-65) at PORT were included in this study. Eighty-one percent of the cohort had positive resection margins while 19% had close margins. At a median follow-up of 92 months, 19/21 patients (90%) had locoregional control. Two patients who failed had primary lesions which recurred locally, and initially had positive margins. The two recurrences occurred at 8 months and 12 months. Acute Radiation Therapy Oncology Group (RTOG) grade 1 and 2 toxicities were experienced by 11 (52%) and 4 (19%) patients, respectively, while 2 (10%) experienced late RTOG grade 1 toxicities. No patients experienced any grade 2-4 late toxicities. Actuarial survival was 100%. CONCLUSION: PORT for patients with pleomorphic adenoma of the parotid gland after resection with close or positive margins results in excellent locoregional control and low treatment-related morbidity.

AIM: Metastasis of unknown primary (MUP) is commonly treated with radiation therapy (RT) to the entire mucosal surfaces and bilateral neck nodes (LN). We report outcomes of oropharynx-targeted RT, retropharyngeal nodes (RPN) and bilateral LN in this context. PATIENTS AND METHODS: Single-Institution retrospective study of 68 patients. Forty percent were treated with intensity-modulated radiation therapy (IMRT). Fifty-six percent received concurrent chemoradiotherapy (CCRT). The median age was 58 years, 82% were Caucasian, and 75% males. Stage III disease was present in 9%, stage IVA in 75% and IVB in 16%. RESULTS: At a median follow-up of 3.5 years, the actuarial locoregional control was 95.5%. The emergence of primary developed in 1patient (1.5%) and 2patients (3%) failed in the neck. The median time-to-locoregional failure (LRF) was 18 months. Actuarial long-term RT toxicity was grade 1 xerostomia (68%), dysphagia (35%), neck stiffness (15%) and trismus (6%). CONCLUSION: RT to the oropharynx, RPN, and bilateral neck provides excellent oncological and functional outcomes in MUP in non-Asian patients. Sparing the mucosal surfaces of the nasopharynx, hypopharynx, and larynx seems reasonable without impacting on survival and locoregional control.

BACKGROUND: Oral mucositis (OM) is a significant toxicity of induction chemotherapy for locally advanced head and neck cancer (LAHNC). The safety and tolerability of AG013, an oral rinse containing recombinant Lactococcus lactis secreting mucosal protectant human trefoil factor 1 (hTFF1), was evaluated in a phase 1b study in LAHNC subjects who received induction with cisplatin, 5-fluorouracil, with or without docetaxel. Preliminary efficacy data were also obtained. METHODS: A total of 25 of 52 LAHNC subjects who were followed during induction cycle 1 developed ulcerative oral mucositis (UOM; World Health Organization grade > 2) and were randomized to AG013:placebo (5:2 ratio) for cycle 2. Dosing schedules of 1, 3, or 6 times daily were evaluated (2 x 10(11) , 6 x 10(11) , and 1.2 x 10(12) colony forming units per day, respectively). OM was evaluated daily from cycle 2, day 1 through 14, using World Health Organization criteria. Pharmacokinetic assessment was also conducted. RESULTS: AG013 bacteria were not detected in blood. Oral live AG013 bacterial and hTFF1 levels in saliva and oral mucosa were equivalent among treatment groups. The most frequently occurring adverse events were nausea, oral pain, fatigue, diarrhea, and mucosal inflammation. Only 12% (3 of 25 adverse events), mainly nausea, were attributed to the investigational medicinal product: AG013 or placebo. Efficacy analysis showed a 35% reduction in percentage of days with UOM in AG013-subjects versus placebo. All placebo subjects experienced >/= 2 days of UOM, whereas 29% of AG013 subjects had UOM for 0 or 1 day. AG013 use resulted in fewer unscheduled office and emergency room visits. No differences were noted in mouth and throat soreness, opioid use, or gastrostomy tube placement. CONCLUSIONS: AG013 was safe and well tolerated. Preliminary efficacy data support further study.