Efficacy of neck treatment in patients with head and neck squamous cell carcinoma.

BACKGROUND: Treatment of head and neck squamous cell carcinoma (HNSCC) addresses the primary tumor and the lymphatic drainage. Modalities for the neck are neck dissection and/or radiation therapy. In most cases, the neck is treated by the modality that seems more appropriate for the primary. The aim of this study was to analyze the results of the neck treatments either by neck dissection alone, by radiation therapy alone or by neck dissection followed by radiation therapy. METHODS: This was a retrospective chart analysis of 699 patients treated for a previously untreated HNSCC. The primary endpoint was recurrence at the treated neck. RESULTS: Two hundred eighty-one (40%) patients underwent primary neck irradiation, 219 (31%) neck dissection alone, and 199 (29%) neck dissection followed by adjuvant irradiation. The 5-year regional control rates after neck dissection alone were 83% for pN0, 75% for pN1, 60% for pN2a, 59% for pN2b, and 50% for pN2c; after radiation alone, 89% for cN0, 87% for cN1, 40% for cN2a, 60% for cN2b, and 48% for cN2c; and after neck dissection with adjuvant radiation, 86% for pN0, 96% for pN1, 100% for pN2a, 88% for pN2b, and 88% for pN2c. CONCLUSIONS: Radiation or neck dissection alone are efficient to control early neck disease. For advanced N2/3 neck disease, neck dissection followed by adjuvant radiation is highly efficient, whereas primary radiation results in a high number of regional failures. The literature suggests planned neck dissection to improve regional control for these patients.

PET/CT staging followed by Intensity-Modulated Radiotherapy (IMRT) improves treatment outcome of locally advanced pharyngeal carcinoma: a matched-pair comparison.

BACKGROUND: Impact of non-pharmacological innovations on cancer cure rates is difficult to assess. It remains unclear, whether outcome improves with 2- [18-F]-fluoro-2-deoxyglucose-positron emission tomography and integrated computer tomography (PET/CT) and intensity-modulated radiotherapy (IMRT) for curative treatment of advanced pharyngeal carcinoma. PATIENTS AND METHODS: Forty five patients with stage IVA oro- or hypopharyngeal carcinoma were staged with an integrated PET/CT and treated with definitive chemoradiation with IMRT from 2002 until 2005. To estimate the impact of PET/CT with IMRT on outcome, a case-control analysis on all patients with PET/CT and IMRT was done after matching with eighty six patients treated between 1991 and 2001 without PET/CT and 3D-conformal radiotherapy with respect to gender, age, stage, grade, and tumor location with a ratio of 1:2. Median follow-up was eighteen months (range, 6-49 months) for the PET/CT-IMRT group and twenty eight months (range, 1-168 months) for the controls. RESULTS: PET/CT and treatment with IMRT improved cure rates compared to patients without PET/CT and IMRT. Overall survival of patients with PET/CT and IMRT was 97% and 91% at 1 and 2 years respectively, compared to 74% and 54% for patients without PET/CT or IMRT (p = 0.002). The event-free survival rate of PET/CT-IMRT group was 90% and 80% at 1 and 2 years respectively, compared to 72% and 56% in the control group (p = 0.005). CONCLUSION: PET/CT in combination with IMRT and chemotherapy for pharyngeal carcinoma improve oncological therapy of pharyngeal carcinomas. Long-term follow-up is needed to confirm these findings.

Osteoradionecrosis of the mandible: minimized risk profile following intensity-modulated radiation therapy (IMRT).

BACKGROUND AND PURPOSE: Osteoradionecrosis (ON) of the mandible is a serious late complication of high-dose radiation therapy for tumors of the oropharynx and oral cavity. After doses between 60 and 72 Gy using standard fractionation, an incidence of ON between 5% and 15% is reported in a review from 1989, whereas in more recent publications using moderately accelerated or hyperfractionated irradiation and doses between 69 and 81 Gy, the incidence of ON is between < 1% and ~ 6%. Intensity-modulated radiation therapy (IMRT) is expected to translate into a further important reduction of ON. The aim of this descriptive study was to assess absolute and relative bone volumes exposed to high IMRT doses, related to observed bone tolerance. PATIENTS AND METHODS: Between December 2001 and November 2004, 73 of 123 patients treated with IMRT were identified as subgroup "at risk" for ON (> 60 Gy for oropharyngeal or oral cavity cancer). 21/73 patients were treated in a postoperative setting, 52 patients underwent primary definitive irradiation. In 56 patients concomitant cisplatin-based chemotherapy was applied. Mean follow-up time was 22 months (12-46 months). Oral cavity including the mandible bone outside the planning target volume was contoured and dose-volume constraints were defined in order to spare bone tissue. Dose-volume histograms were obtained from contoured mandible in each patient and were analyzed and related to clinical mandible bone tolerance. RESULTS: Using IMRT with doses between 60 and 75 Gy (mean 67 Gy), on average 7.8, 4.8, 0.9, and 0.3 cm(3) were exposed to doses > 60, 65, 70, and 75 Gy, respectively. These values are substantially lower than when using three-dimensional conformal radiotherapy. The difference has been approximately quantified by comparison with a historic series. Additional ON risk factors of the patients were also analyzed. Only one grade 3 ON of the lingual horizontal branch, treated with lingual decortication, was observed. CONCLUSION: Using IMRT, only very small partial volumes of the mandibular bone are exposed to high radiation doses. This is expected to translate into a further reduction of ON and improved osseointegration of dental implants.

Growth retardation and bilateral cataracts followed by anaplastic meningioma 23 years after high-dose cranial and whole-body irradiation for acute lymphoblastic leukemia: case report and review of the literature.

We report a case of meningioma diagnosed 23 years after high-dose cranial and whole-body irradiation for the treatment of acute lymphocytic leukemia (ALL). Radiotherapy in this case also caused early radiation injury to the lenses and the pituitary gland, with growth retardation and mineralizing angiopathy. Radiation-induced meningiomas are more commonly malignant, more commonly multiple, and more likely to recur after resection than non-radiation-induced meningiomas. Survivors of childhood ALL treated with high-dose cranial irradiation are at risk both for early radiation injury in radiosensitive organs, such as the lens and pituitary gland, and for the later development of a radiation-induced meningioma.

Risk factors for developing a second upper aerodigestive cancer after radiotherapy with or without chemotherapy in patients with head-and-neck cancers: an exploratory outcomes analysis.

PURPOSE: The objective was to assess the influence of treatment-related and patient-related factors on the risk of developing a second primary tumor (SPT) of the upper aerodigestive tract (UADT) in patients with locoregionally advanced nonmetastatic carcinomas of the head-and-neck region. METHODS AND MATERIALS: The data of 521 patients with a minimum follow-up of 1 year were pooled: 224 patients from the Swiss Group for Clinical Cancer Research (SAKK) 10/94 trial, treated with 1.2 Gy b.i.d. to 74.4 Gy, and randomized to receive or not to receive simultaneous chemotherapy with cisplatin (excluding nasopharyngeal and maxillary sinus carcinomas); and 297 patients from Geneva, all treated with accelerated radiotherapy with concomitant boost to 69.9 Gy and predominantly cisplatin-based concomitant chemotherapy in 33% of patients (including 21 patients with nasopharyngeal carcinomas). An exploratory analysis using competing risk methodology was performed. RESULTS: A total of 65 SPT of the UADT were observed after a median observation time of 4.7 years. The overall risk of experiencing an SPT of the UADT at 10 years in the presence of all other possible events was estimated to be 33%. There were no SPTs after treatment for nasopharyngeal carcinoma. In a multivariate logistic regression analysis, there was no difference in occurrence of SPT at 3 years with respect to the administration of chemotherapy (p = 0.31), age (p = 0.62), performance status (p = 0.61), gender (p = 0.27), presence of nodal disease (p = 0.51), or T stage (p = 0.72). However, patients treated with concomitant boost had fewer SPTs (p = 0.0093). CONCLUSIONS: Our data do not suggest that addition of chemotherapy to radiotherapy influences the incidence of second cancers in patients with head-and-neck cancer. The difference in the incidence of SPT between the two radiotherapy schedule groups merits further exploration.

Concomitant cisplatin significantly improves locoregional control in advanced head and neck cancers treated with hyperfractionated radiotherapy.

PURPOSE: To determine whether the application of two courses of cisplatin simultaneously with hyperfractionated radiotherapy improves the outcome in locally advanced and/or node-positive nonmetastatic carcinomas of the head and neck, compared with hyperfractionated radiotherapy alone. PATIENTS AND METHODS: From July 1994 to July 2000, 224 patients with squamous cell carcinomas of the head and neck (excluding nasopharynx and paranasal sinus) were randomly assigned to hyperfractionated radiotherapy (median dose, 74.4 Gy; 1.2 Gy twice daily) or the same radiotherapy combined with two cycles of concomitant cisplatin (20 mg/m2 on 5 days of weeks 1 and 5). The primary end point was time to any treatment failure; secondary end points were locoregional failure, metastatic relapse, overall survival, and late toxicity. RESULTS: There was no difference in radiotherapy between both treatment arms (74.4 Gy in 44 days). The full cisplatin dose was applied in 93% and 71% of patients during the first and second treatment cycles, respectively. Acute toxicity was similar in both arms. Median time to any treatment failure was not significantly different between treatment arms (19 months for combined treatment and 16 months for radiotherapy only, respectively) and the failure-free rate at 2.5 years was 45% and 33%, respectively. Locoregional control and distant disease-free survival were significantly improved with cisplatin (log-rank test, P = .039 and .011, respectively). The difference in overall survival did not reach significance (log-rank test, P = .147). Late toxicity was comparable in both treatment groups. CONCLUSION: The therapeutic index of hyperfractionated radiotherapy is improved by concomitant cisplatin.

Positron emission tomography in the early follow-up of advanced head and neck cancer.

OBJECTIVE: To assess the clinical effect of an early follow-up positron emission tomography (PET) examination at the time of the first routine clinical control in patients with advanced-stage head and neck squamous cell carcinoma (HNSCC). DESIGN: Prospective, nonrandomized, case-control study. SETTING: Single referral center. PATIENTS AND INTERVENTION: A total of 26 patients (mean age, 56 years) with histologically confirmed stage III-IV HNSCC underwent PET before and approximately 6 weeks after the end of a combined treatment with radiation and chemotherapy with curative intent. The PET findings were confirmed by histologic analysis and a 6-month clinical follow-up. MAIN OUTCOME MEASURES: The presence of distant metastases, secondary synchronous cancers, and residual locoregional tissue was confirmed, and the effect on further clinical management was assessed. RESULTS: Using PET, we correctly identified residual tumor tissue, distant metastases, or a second primary tumor in 10 patients, 5 of whom had no clinical evidence of such findings. Results were true negative in 14 cases; false positive in 1; and false negative in 1. Sensitivity and specificity for follow-up PET scans were 90.9% and 93.3%, respectively. All patients with positive findings were evaluated for further treatment such as salvage surgery. CONCLUSIONS: Whole-body PET scanning approximately 6 weeks after completion of a combined treatment regimen with radiation and chemotherapy can reliably identify locoregional residual cancer and distant metastases or secondary tumors in patients with advanced-stage HNSCC and has a direct influence on management decisions.

Early glottic carcinoma: treatment according patient's preference?

BACKGROUND: To analyze the results in early (stage I and II) glottic carcinoma of a single institution with a patient-oriented concept. METHODS: After diagnostic workup and multidisciplinary counseling, either radiotherapy or CO(2) laser surgery was chosen with respect to the patient's preference. RESULTS: Sixty-five patients underwent laser surgery and 75 had radiotherapy. For T1 tumors, the 5-year overall survival, disease-specific survival, and initial local control rate after laser surgery and radiotherapy were comparable (OS, 85% vs 88%; DSS, 96% vs 93%; LCR, 86% vs 85%). In contrast, initial local control for T2 tumors was significantly more favorable after surgery (OS, 83% vs 78%; DSS, 83% vs 88%; LCR, 89% vs 67%). Larynx preservation was significantly higher after surgery in T1 tumors (96% vs 82%) and in T2 tumors (89% vs 77%). CONCLUSIONS: Selection of the treatment modality according to patient's preference results in a comparable control of disease for T1 tumors. The initial local control for T2 tumors is significantly better after surgery. In both stages laser surgery warrants a better larynx preservation rate.

Early morbidity after radiotherapy with or without chemotherapy in advanced head and neck cancer. Experience from four nonrandomized studies.

BACKGROUND: Data on early treatment-related morbidity after radiotherapy alone (RT; 217 patients) or combined with chemotherapy (RT + CT; 182 patients) of head and neck squamous cell carcinoma are analyzed. PATIENTS AND METHODS: The patients were treated between November 1985 and November 1996 in four Swiss centers that independently introduced combined-modality therapy in selected cases of head and neck cancer. RT schedules varied among the four centers, but within each institution all patients received the same dose-fractionation schedule irrespective of whether they had CT or not. The following early morbidity items were evaluated: skin, mucosa, larynx, salivary glands, dysphagia, weight loss, and toxic death. Toxicity was scored using the EORTC/RTOG scale. RESULTS: Although considerable variation was noted among the treatment schedules/centers, the main findings are as follows: (1) early morbidity was significantly enhanced after all five RT + CT schedules compared with RT alone; (2) typically, a third of the patients lost > 10% of their body weight during concurrent RT + CT as compared with 10% of the patients receiving RT alone; (3) at 12 weeks, the prevalence of grade 2 morbidity was 25-60% after RT + CT as compared with 4-20% after RT alone. CONCLUSION: A number of early morbidity items were found to be more prevalent and/or more severe after RT + CT than after RT alone.

Impact of positron emission tomography on the initial staging and therapy in locoregional advanced squamous cell carcinoma of the head and neck.

OBJECTIVE: To evaluate the impact of 18F-fluoro-deoxy-glucose positron emission tomography after standard diagnostic workup in patients with advanced head and neck squamous cell carcinoma on staging and radiation treatment planning. STUDY DESIGN: Prospective controlled study. METHODS: Forty-eight patients (42 men and 6 women; mean age, 61 y; age range, 35-85 y) with histologically confirmed, advanced-stage (any T, N> or =N2 or T> or =T3, any N) mucosal head and neck squamous cell carcinoma underwent positron emission tomography. The routine workup consisting of physical examination, panendoscopy, chest x-ray film, and contrast-enhanced high-resolution helical computed tomography scan (HRCT) was used for comparison. End points were the extent of lymph node disease, distant metastases, and second primary tumors. RESULTS: In 41 of 48 patients (85%) the lymph node findings between HRCT and positron emission tomography were concordant. In three patients positron emission tomography led to an upstaging of the tumor in its N category, and in four patients positron emission tomography underestimated lymph node involvement. Positron emission tomography revealed more difficulties in delineating lymph node metastases adjacent to the primary tumor than did HRCT, but was superior for the detection of distant and contralateral lymph node metastases. Positron emission tomography suggested distant metastatic lesions in 6 of 48 patients (13%). Cytological workup confirmed distant metastases in two (4%) and second primary tumors in another two patients (4%). Positron emission tomography results were false-positive in two (4%) patients because of inflammatory changes. CONCLUSIONS: Whole-body PET is able to assess lymph node involvement, distant metastases, and second primaries in a single study. Even after a routine clinical staging, positron emission tomography leads to a change of treatment in approximately 8% of patients.