Michael Betz

Mandibular Osteoradionecrosis in Squamous Cell Carcinoma of the Oral Cavity and Oropharynx Incidence and Risk Factors

Objective. Mandibular osteoradionecrosis (ORN) is a serious complication of radiotherapy (RT) in head and neck cancer patients. The aim of this study was to analyze the incidence of and risk factors for mandibular ORN in squamous cell carcinoma (SCC) of the oral cavity and oropharynx. Study Design. Case series with chart review. Setting. University tertiary care center for head and neck oncology. Subjects and Methods. Seventy-three patients treated for stage I to IV SCC of the oral cavity and oropharynx between 2000 and 2007, with a minimum follow-up of 2 years, were included in the study. Treatment modalities included both RT with curative intent and adjuvant RT following tumor surgery. The log-rank test and Cox model were used for univariate and multivariate analyses. Results. The incidence of mandibular ORN was 40% at 5 years. Using univariate analysis, the following risk factors were identified: oral cavity tumors (P < .01), bone invasion (P < .02), any surgery prior to RT (P < .04), and bone surgery (P < .0001). By multivariate analysis, mandibular surgery proved to be the most important risk factor and the only one reaching statistical significance (P < .0002). Conclusion. Mandibular ORN is a frequent long-term complication of RT for oral cavity and oropharynx cancers. Mandibular surgery before irradiation is the only independent risk factor. These aspects must be considered when planning treatment for these tumors.

Concomitant Cisplatin and Hyperfractionated Radiotherapy in Locally Advanced Head and Neck Cancer: 10-Year Follow-Up of a Randomized Phase III Trial (SAKK 10/94)

PURPOSE To compare the long-term outcome of treatment with concomitant cisplatin and hyperfractionated radiotherapy versus treatment with hyperfractionated radiotherapy alone in patients with locally advanced head and neck cancer. METHODS AND MATERIALS From July 1994 to July 2000, a total of 224 patients with squamous cell carcinoma of the head and neck were randomized to receive either hyperfractionated radiotherapy alone (median total dose, 74.4 Gy; 1.2 Gy twice daily; 5 days per week) or the same radiotherapy combined with two cycles of cisplatin (20 mg/m(2) for 5 consecutive days during weeks 1 and 5). The primary endpoint was the time to any treatment failure; secondary endpoints were locoregional failure, metastatic failure, overall survival, and late toxicity assessed according to Radiation Therapy Oncology Group criteria. RESULTS Median follow-up was 9.5 years (range, 0.1-15.4 years). Median time to any treatment failure was not significantly different between treatment arms (hazard ratio [HR], 1.2 [95% confidence interval {CI}, 0.9-1.7; p = 0.17]). Rates of locoregional failure-free survival (HR, 1.5 [95% CI, 1.1-2.1; p = 0.02]), distant metastasis-free survival (HR, 1.6 [95% CI, 1.1-2.5; p = 0.02]), and cancer-specific survival (HR, 1.6 [95% CI, 1.0-2.5; p = 0.03]) were significantly improved in the combined-treatment arm, with no difference in major late toxicity between treatment arms. However, overall survival was not significantly different (HR, 1.3 [95% CI, 0.9-1.8; p = 0.11]). CONCLUSIONS After long-term follow-up, combined-treatment with cisplatin and hyperfractionated radiotherapy maintained improved rates of locoregional control, distant metastasis-free survival, and cancer-specific survival compared to that of hyperfractionated radiotherapy alone, with no difference in major late toxicity.

Adenosquamous carcinoma of the head and neck: report of 20 cases and review of the literature

PURPOSE To assess the clinical profile and prognostic factors in patients with adenosquamous carcinoma (ASC) of the head and neck treated by surgery and/or radiation therapy with or without chemotherapy. METHODS Data from 20 patients with stage I-II (n = 4), III (n = 5), or IVA (n = 11) head and neck ASC, treated between 1989 and 2010 were collected in a retrospective multicenter Rare Cancer Network study. Surgery was performed in 16 patients. Seventeen patients received combined modality treatment. RESULTS After a median follow-up of 15.5 months, 12 patients recurred. The 3-year and median overall survival, disease-free survival (DFS), and loco-regional control were 52% and 39 months, 32% and 12 months, and 47% and 33 months respectively. In multivariate analysis, DFS was negatively influenced by the presence of extracapsular extension and advanced stage. CONCLUSION Overall prognosis of locoregionally advanced ASC remains poor. However, early stage ASC patients managed with combined modality treatment may have prolonged DFS.

Effectiveness of intensity-modulated and image-guided radiotherapy to spare the mandible from excessive radiation

We would like to assess the effectiveness of intensity-modulated radiotherapy (IMRT) or image-guided radiotherapy (IGRT) to decrease the risk of osteoradionecrosis in locally advanced head and neck cancer. We conducted a retrospective study of 83 patients with head and neck cancer undergoing concurrent definitive chemoradiation, post-operative radiotherapy or chemoradiation, or radiotherapy alone with IMRT or IGRT. Mean mandibular dose was, respectively, 43.6Gy and 43.8Gy for the IMRT and IGRT technique. At a median follow-up of 28 months (5-55 months), only one patient developed osteoradionecrosis requiring hyperbaric oxygen. Sharp dose falloff associated with IMRT and IGRT decreased excessive radiation of the mandible and may reduce the risks of osteoradionecrosis.

Feasibility of Intensity-Modulated and Image-Guided Radiotherapy for Functional Organ Preservation in Locally Advanced Laryngeal Cancer

Purpose The study aims to assess the feasibility of intensity-modulated and image-guided radiotherapy (IMRT, and IGRT, respectively) for functional preservation in locally advanced laryngeal cancer. A retrospective review of 27 patients undergoing concurrent chemoradiation for locally advanced laryngeal cancers (8 IMRT, 19 IGRT) was undertaken. In addition to regular clinical examinations, all patients had PET imaging at 4 months and 10 months after radiotherapy, then yearly. Loco-regional control, speech quality and feeding-tube dependency were assessed during follow-up visits. Results At a median follow-up of 20 months (range 6–57 months), four out of 27 patients (14.8%) developed local recurrence and underwent salvage total laryngectomy. One patient developed distant metastases following salvage surgery. Among the 23 patients who conserved their larynx with no sign of recurrence at last follow-up, 22 (95%) reported normal or near normal voice quality, allowing them to communicate adequately. Four patients (14.8%) had long-term tube feeding-dependency because of severe dysphagia (2 patients) and chronic aspiration (2 patients, with ensuing death from aspiration pneumonia in one patient). Conclusions and Clinical Relevance Functional laryngeal preservation is feasible with IMRT and IGRT for locally advanced laryngeal cancer. However, dysphagia and aspiration remain serious complications, due most likely to high radiation dose delivery to the pharyngeal musculatures.

Impact of image-guided radiotherapy to reduce laryngeal edema following treatment for non-laryngeal and non-hypopharyngeal head and neck cancers

We would like to determine the effectiveness of image-guided radiotherapy (IGRT) to reduce laryngeal edema following treatment for head and neck cancer and to assess patient perception of voice and speech after treatment. We conducted a retrospective review of 44 patients undergoing radiation for non-laryngeal and non-hypopharyngeal head and neck cancers. Endoscopic and/or mirror examinations of the larynx were performed following radiotherapy at each follow-up visit. Laryngeal edema was assessed based on the Radiation Therapy Oncology Group grading scale. Patients were also asked to rate about the voice and speech quality relative to their pre-radiotherapy status. The mean laryngeal dose was 16.3 Gy (range: 11.7-45.5 Gy). At a median follow-up of 14 months (range: 2-31 months), three patients (7%) developed laryngeal edema (one grade 1, two grade 2). The mean laryngeal dose was respectively 20.3 Gy in two patients and 20.7 Gy in the third patient developing laryngeal edema. Except for one patient who continued to smoke and drink after radiotherapy, no patient reported any significant change in voice and speech quality after treatment. IGRT results in low rates and low severity of laryngeal edema following treatment for non-laryngeal and non-hypopharyngeal head and neck cancers and may preserve voice quality.

Elective inguinal node irradiation in early-stage T2N0 anal cancer: prognostic impact on locoregional control

PURPOSE To evaluate the influence of elective inguinal node radiation therapy (INRT) on locoregional control (LRC) in patients with early-stage T2N0 anal cancer treated conservatively with primary RT. METHODS AND MATERIALS Between 1976 and 2008, 116 patients with T2 node-negative anal cancer were treated curatively with RT alone (n=48) or by combined chemoradiation therapy (CRT) (n=68) incorporating mitomycin C and 5-fluorouracil. Sixty-four percent of the patients (n=74) received elective INRT. RESULTS Over a median follow-up of 69 months (range, 4-243 months), 97 (84%) and 95 patients (82%) were locally and locoregionally controlled, respectively. Rates for 5-year actuarial local control, LRC, cancer-specific, and overall survival for the entire population were 81.7% ± 3.8%, 79.2% ± 4.1%, 91.1% ± 3.0%, and 72.1% ± 4.5%, respectively. The overall 5-year inguinal relapse-free survival was 92.3% ± 2.9%. Isolated inguinal recurrence occurred in 2 patients (4.7%) treated without INRT, whereas no groin relapse was observed in those treated with INRT. The 5-year LRC rates for patients treated with and without INRT and with RT alone versus combined CRT were 80.1% ± 5.0% versus 77.8% ± 7.0% (P=.967) and 71.0% ± 7.2% versus 85.4% ± 4.5% (P=.147), respectively. A trend toward a higher rate of grade ≥3 acute toxicity was observed in patients treated with INRT (53% vs 31%, P=.076). CONCLUSIONS In cases of node-negative T2 anal cancer, the inguinal relapse rate remains relatively low with or without INRT. The role of INRT in the treatment of early-stage anal carcinoma needs to be investigated in future prospective trials.

Feasibility of Tomotherapy-Based Image-Guided Radiotherapy for Locally Advanced Oropharyngeal Cancer

PURPOSE The study aims to assess the feasibility of tomotherapy-based image-guided (IGRT) radiotherapy for locally advanced oropharyngeal cancer. A retrospective review of 33 patients undergoing concurrent chemoradiation for locally advanced oropharyngeal cancers was conducted. Radiotherapy planning, treatment toxicity and loco-regional control were assessed. RESULTS At a median follow-up of 32 months (6-47 months), no patient developed loco-regional recurrence. Two patients (6%) developed distant metastases. Grade 3-4 acute toxicity was respectively 72% and 25% for mucositis and gastrointestinal toxicity. Two patients (6%) had long-term dependence on tube feedings. Dose-volume histogram demonstrated excellent target volume coverage and low radiation dose to the organs at risk for complications. CONCLUSIONS AND CLINICAL RELEVANCE IGRT provides excellent loco-regional control but acute toxicity remains significant and needs to be addressed in future prospective trials. The feasibility of Tomotherapy to decrease radiation dose to the normal tissues merits further investigations.

Effectiveness of prophylactic retropharyngeal lymph node irradiation in patients with locally advanced head and neck cancer

BackgroundThe aim of the study is to assess the effectiveness of intensity-modulated radiotherapy (IMRT) or image-guided radiotherapy (IGRT) for the prevention of retropharyngeal nodal recurrences in locally advanced head and neck cancer.MethodsA retrospective review of 76 patients with head and neck cancer undergoing concurrent chemoradiation or postoperative radiotherapy with IMRT or IGRT who were at risk for retropharyngeal nodal recurrences because of anatomic site (hypopharynx, nasopharynx, oropharynx) and/or the presence of nodal metastases was undertaken.The prevalence of retropharyngeal nodal recurrences was assessed on follow-up positron emission tomography (PET)-CT scans.ResultsAt a median follow-up of 22 months (4–53 months), no patient developed retropharyngeal nodal recurrences.ConclusionProphylactic irradiation of retropharyngeal lymph nodes with IMRT or IGRT provides effective regional control for individuals at risk for recurrence in these nodes.

Image-Guided Radiotherapy for Locally Advanced Head and Neck Cancer

Treatment of locally advanced head and neck cancer remains a challenge because of the head and neck complex anatomy and the tumor invasion to the adjacent organs and/or metastases to the cervical nodes. Postoperative irradiation or concurrent chemoradiation may lead to damage of radiosensitive structures such as the salivary glands, mandible, cochlea, larynx, and pharyngeal muscles. Xerostomia, osteoradionecrosis, deafness, hoarseness of the voice, dysphagia, and aspiration remain serious complications of head and neck irradiation and impair patient quality of life. Intensity-modulated and image-guided radiotherapy by virtue of steep dose gradient and daily imaging may allow for decreased radiation of the organs at risk for complication while preserving loco-regional control.