Laryngeal long-term morbidity after supraglottic laryngectomy and postoperative radiation therapy.

PURPOSE: This study was performed to investigate factors associated with laryngeal morbidity when postoperative radiation therapy (RT) is added to supraglottic laryngectomy. MATERIALS AND METHODS: From 1980 to 1994, 56 patients affected with T1 to 4 N0 to 2c supraglottic squamous cell carcinoma selected for standard (59%) or extended (41%) supraglottic laryngectomy at 2 different institutions were retrospectively analyzed. Most of the patients (91%) also underwent neck dissection. Approximately 80% of the patients had stage T4 primary lesions or N2 neck disease. Postoperative RT was added for presumed microscopic disease at the primary site (13 patients), regional nodes (23 patients), or both (20 patients). Median delivered doses to the larynx and to the neck were 50 Gy (range, 40 to 64 Gy) and 46 Gy (range, 40 to 64 Gy), respectively. Median follow-up for living patients is 11 years (range, 2.8 to 16.9 years). Laryngeal complication was defined as the appearance of grade 2 or higher toxicity according to the European Organization for Research and Treatment of Cancer (EORTC) and the Radiation Therapy Oncology Group (RTOG) scoring systems. RESULTS: Two- and 5-year actuarial locoregional control rates were 85+/-5% and 83+/-5%, respectively. Thirty patients (54%) developed laryngeal complications. However, just one patient experienced grade 4 laryngeal oedema requiring permanent tracheostomy. Estimated actuarial survival without laryngeal complications were 50+/-7%, 43+/-7%, and 39+/-7% at 2, 5, and 10 years, respectively. At univariate analysis, treated volumes (P = .03) and total dose to the larynx (P = .03) were significantly associated with local toxicity. A trend was observed also for the maximum dose to the neck (P = .06) and dose per fraction (P = .09). A multivariate Cox proportional hazards model showed total dose to the larynx to be the only independent predictor of toxicity (P = .03). The hazard ratio of laryngeal toxicity was 2.2 (95% confidence interval: 1.1/4.6), for a total dose to the larynx greater than 50 Gy. CONCLUSION: After supraglottic laryngectomy, postoperative RT to the neck does not affect local morbidity, but careful RT treatment planning is necessary to avoid delivering a total dose to the larynx greater than 50 Gy.

[Role of palliative and symptomatic radiotherapy in bone metastasis]. / Il ruolo della radioterapia palliativa e sintomatica delle metastasi ossee.

INTRODUCTION: The presence of bone metastases is a common event in the natural history of nearly all neoplasms which often affects the patient's quality of life greatly. Bone metastases may cause pain and pathologic fractures, or even a cord compression syndrome with severe neurologic symptoms. We tried to assess the optimal irradiation schedule for these patients and to discuss the use of radiopharmaceuticals. MATERIALS AND METHODS: We reviewed the literature focusing on studies investigating the efficacy of hypofractionated radiotherapy for bone metastases. We also addressed the problem of treating multiple skeletal lesions with half-body irradiation and radionuclides. RESULTS: External beam irradiation achieves pain palliation in more than 75% of patients with bone metastases, even with hypofractionation down to a single-dose administration. The results of exclusive radiotherapy in the cord compression syndrome depend on a prompt diagnosis, patient presentation and the intrinsic radiosensitivity of tumor cells. Palsy can always be avoided in these patients. Half-body irradiation can achieve complete pain relief in over 20% of patients and decrease pain markedly in the remaining cases with only a single-dose fraction (6-10 Gy), within 48 hours of irradiation and with little side-effects. Better results in terms of pain relief (80% complete responses) and duration of palliation come from fractionated half-body irradiation (up to 17.5 Gy in 7 fractions), which however has a more delayed response (1-2 weeks) and higher toxicity. The use of radiopharmaceuticals has been recently reevaluated after the introduction of new nuclides: results are similar to those of external beam irradiation (up to 80% responses), but cost and hematologic toxicity are both high. Radiopharmaceuticals can be used within an integrated treatment with external beam irradiation, chemotherapy and biphosphonates. DISCUSSION: The efficacy of external beam irradiation in the palliation of bone metastasis-related symptoms is confirmed by this literature review, even with short treatments and single-dose administrations. This is important for both patient expectations and the necessity for improved resource allocation with reference to the territorial distribution and waiting lists of radiotherapy centers. Finally, as for the role of radiopharmaceuticals, the best nuclides are not widely used yet for the high cost of the treatment, even though they provide similar results to external beam irradiation. The issue of their efficacy in combination with antiblastic drugs and/or external beam irradiation remains open and will be clarified only with further randomized clinical trials.

Combined modality treatment for esophageal cancer.

This paper describes the mechanisms of action of ionizing radiations combined with antineoplastic drugs. Some relevant drugs for the combined modality treatments of locally advanced lung cancer are reported. The meta-analyses including randomized trials comparing single agent (radiotherapy or chemotherapy) versus combined chemotherapy and radiotherapy in patients with unresectable non small cell lung cancer and limited small cell lung cancer are then reviewed. The clinical outcome in relation to different schedules of chemoradiotherapy (sequential, alternating and concurrent) is also focussed.

The predictive role of flow cytometry-derived tumor potential doubling time (Tpot) in radiotherapy: open questions and future perspectives.

Measurement of tumor-cell kinetic parameters, following in vivo administration of thymidine analogues and bivariate flow cytometry, allows quantitative cell kinetic determinations in a clinically relevant time-scale, potentially useful for selection of individual radiotherapy schedules. Among the dynamic cell kinetic parameters that can be measured using the in vivo method, the tumor potential doubling time (Tpot), defined as the time to double the number of proliferating tumor cells in the absence of cell loss, has been postulated to be a predictor of a tumor's proliferative capability, thus representing a potential predictive factor of local control after irradiation. So far, published data have shown the safety and feasibility of the technique, even in multicenter studies, and demonstrated a wide range of parameter values in many tumor sites. With only a few exceptions the hypothesis that Tpot is an independent prognostic indicator cannot be considered proven yet. We review the major controversial issues and open questions, mainly in the area of data production and analysis, that must be resolved before the predictive role of Tpot is unequivocally defined. The future of radiotherapy predictive assays lies in the development of multiparametric studies, accounting for multiple factors of radiation response, which may prove of greater prognostic significance than any single parameter approach based only on cell kinetics.

Conservative management of T1-T2N0 supraglottic cancer: a retrospective study.

PURPOSE: Evaluate the results of conservative management of early-stage supraglottic cancer. PATIENTS AND METHODS: A retrospective analysis of 166 consecutive T1-T2N0 cases of squamous cell carcinoma of the supraglottic larynx, treated conservatively between 1983 and 1992, was performed. Sixty-six patients received conservative surgery (CS), whereas 100 patients received definitive radiation therapy (RT). Surgical procedures included horizontal supraglottic laryngectomy in 38 patients, extended supraglottic laryngectomy in 16 patients, and reconstructive laryngectomy with cricohyoidopexy in 12 patients. Elective bilateral neck dissection was always performed. Radiotherapy was delivered with 60Co or 6 MV photons to the primary laryngeal tumor and the upper and mid neck nodes (level II and III), whereas supraclavicular nodes (level IV) were electively irradiated only in 54 patients with T2N0 tumors. Fifty-two patients received conventional fractionation, whereas 31 patients were irradiated according to a twice-a-day fractionation regimen. The median total tumor dose was 67 Gy (range, 64 to 72 Gy). RESULTS: The 5-year overall survival of the whole series was 72.7% +/- 4.5. In patients treated with CS, the 5-year disease-free survival was 88.4% +/- 4.5 versus 76.4% +/- 6.1 for patients who received RT. Salvage surgery was effective in rescuing 2 of 3 CS failures and 12 of 25 RT failures. The overall incidence of secondary tumors (11%) and distant metastases (5%) was relatively low, although together they account for 15% of all deaths. Complications of CS were significantly correlated to the extent of surgical procedure. A multivariate analysis performed in the RT group showed that performance status, tumor grade, and fractionation regimen significantly influenced disease-free survival. CONCLUSION: Conservative management of T1-T2N0 supraglottic cancer, either by CS or RT, can achieve good cure rates with larynx preservation for the majority of the patients (82% overall; 95% in the CS group and 72% in the RT group). The decision between different conservative treatment modalities may be influenced by the patient's conditions, tumor characteristics, treatment modalities, and also economic costs.

[Radiotherapy of cutaneous cervical-facial carcinomas]. / La radioterapia dei carcinomi cutanei cervico-facciali.

The main goal of therapy for epithelial skin cancer is cure with the best functional and cosmetic outcome. Both surgery and radiotherapy give similar results for early stage lesions with 5-year local control rates ranging from 85% to 95%. Remarkable technological progress has been made yielding well defined indications to radiotherapy as a single treatment or in the context of a multidisciplinary approach. Selection of treatment should be tailored considering anatomic site, surface conformation, size, histology, grading and characteristics of tumours (new occurrence, relapse), number of localizations, age and medical conditions of the single patient. Surgery, guided by intraoperative control of resection margins, is undoubtedly the therapy of choice for most of early stage lesions. Radiation therapy plays an important role in specific anatomic situations in which the functional or cosmetic result is better than for a surgical modality, electively for the treatment of multiple lesions and for large deep- infiltrating carcinomas that generally are not suitable to excision. Exclusive radiotherapy is also indicated as rescue treatment of surgical relapses no more amenable to reexcision as well as for palliation of advanced cases, mainly for elderly or medically compromised patients. Postoperative irradiation should be considered for macro or microscopic residual disease. Merkel cell or adnexal carcinomas and for highly recurrent lesions after repeated surgery. Treatment results and complications of radiotherapy are discussed, emphasizing high local control rates and good functional and cosmetic outcomes. The main irradiation techniques referred to specific anatomic sites are also presented.