Stereotactic radiotherapy (SRT) for differentiated thyroid cancer (DTC) oligometastases: an AIRO (Italian association of radiotherapy and clinical oncology) systematic review.

PURPOSE: The aim of this systematic review was to examine efficacy of stereotactic radiotherapy (SRT) in patients with oligometastatic thyroid cancer. MATERIALS AND METHODS: A systematic search was conducted by means of PubMed, Scopus, and Cochrane library. CLINICALTRIALS: gov was searched for ongoing or recently completed trials, and PROSPERO was searched for ongoing or recently completed systematic reviews. We analyzed only clinical studies as full text carried out on patients with oligometastatic thyroid cancer treated with SRT. Conference papers, surveys, letters, editorials, book chapters, and reviews were excluded. Time of publication was restricted to the years 1990-2021. RESULTS: The number of evaluated patients was 146 (267 lesions), and the median age was 58 years. The median 1-year local control (LC) was 82% (range 67.0%-97.1%); the median disease-free survival (DFS) was 12 months (range 4-53); the median 1-year overall survival was 72% (range 66.6%-85.0%); the 3-year cancer-specific survival was 75.0%; and the 4-year cancer-specific survival was 37.5%. No grade 3-5 acute toxicity was reported. No late effects were recorded. CONCLUSIONS: SRT for oligometastases from thyroid cancer as salvage therapy is well tolerated and yields high rates of LC and prolonged DFS.

Prognostic significance of neutrophil-to-lymphocyte ratio in HPV status era for oropharyngeal cancer.

AIM: To evaluate the role of baseline neutrophil-to-lymphocyte ratio (NLR) as prognostic marker in squamous cell carcinoma of the oropharynx (OPC) treated with definitive chemoradiotherapy (CRT) in the era of HPV status. PATIENTS AND METHODS: A retrospective analysis of 125 patients (pts) affected with locally advanced OPC was performed. Inclusion criteria were age >18 years, stage III or IV (TNM 7th ed.) and definitive CRT. Haematological marker for their independent role as prognostic biomarkers for progression-free survival (PFS) and overall survival (OS). Logistic models were used to assess the association with downstage in TNM 8th ed. RESULTS: Seventy-seven (61.6%) pts had HPV/p16 + related OPC. Therapeutic choice consisted in sequential and concurrent CRT. Median follow-up was 50 months. A value of NLR ≥3 was associated with poorer OS. Two-year OS was 91% and 81% in pts with NLR <3 and ≥3, respectively. CONCLUSION: A baseline NLR ≥ 3 at treatment initiation represented a negative prognostic marker for OPC treated with definitive CRT. These results are in line with literature data, and prognostic value of NLR has been confirmed restaging our cohort with new TNM staging (8th ed.). Therefore, NLR could be considered a valuable biomarker for risk stratification in pts with OPC.

Cell-free DNA as a prognostic marker in stage I non-small-cell lung cancer patients undergoing stereotactic body radiotherapy.

OBJECTIVE: To evaluate whether plasma cell-free DNA (cfDNA) was related to clinical outcome in inoperable stage I non-small cell lung cancer (NSCLC) patients undergoing stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: Plasma cfDNA was assessed at baseline, before the last day and 45 days after the end of SBRT, in 22 NSCLC patients. Twenty-two healthy controls were also evaluated. RESULTS: Plasma cfDNA was higher in patients than in controls. An association with unfavourable disease-free survival was found for continuous baseline cfDNA increments (HR = 5.9, 95%CI: 1.7-19.8, p = 0.04). CONCLUSION: Plasma cfDNA may be a promising prognostic biomarker in high-risk NSCLC patients.

Concurrent chemoradiotherapy with tomotherapy in locally advanced Non-Small Cell Lung Cancer: a phase I, docetaxel dose-escalation study, with hypofractionated radiation regimen.

BACKGROUND: Concurrent chemo-radiotherapy is demonstrately superior to sequential chemo-radiotherapy in the treatment of advanced Non-Small-Cell Lung Cancer not suitable for surgery. Docetaxel is considered to enhance the cytotoxic effect of radiotherapy on the tumour cells. Tomotherapy (HT) is a novel radiotherapeutic technique, which allows the delivery of Image Guided-IMRT (IG-IMRT), with a highly conformal radiation dose distribution.The goal of the study was to estimate tolerability of Docetaxel concurrent with IMRT and to find the maximum tolerated dose of weekly Docetaxel concurrent with IMRT delivered with HT Tomotherapy after induction chemotherapy with Cisplatin and Docetaxel in patients affected with stage III Non-Small Cell Lung Cancer. METHODS: We designed a phase I, dose-finding study to determine the dose of weekly Docetaxel concurrent with Tomotherapy after induction chemotherapy, in patients affected by Non-Small Cell Lung Cancer with Stage III disease, not suitable for surgery. RESULTS: Concurrent weekly Docetaxel and Tomotherapy are feasible; we did not reach a maximum tolerated dose, because no life-threatening toxicity was observed, stopping the accrual at a level of weekly docetaxel 38 mg/m2, a greater dose than in previous assessments, from both phase-I studies with weekly docetaxel alone and with Docetaxel concomitant with standard radiotherapy. CONCLUSIONS: Concurrent weekly Docetaxel and Tomotherapy are feasible, and even with Docetaxel at 38 mg/m2/week we did not observe any limiting toxicity. For those patients who completed the combined chemo-radio treatment, median progression-free survival (PFS) was 20 months and median overall survival (OS) was 24 months.

Thyroidectomies in Italy: A Population-Based National Analysis from 2001 to 2018.

Background: The incidence of thyroid disease is generally increasing, and it is subject to major geographic variability, between and within countries. Moreover, the incidence rates and the proportion of overdiagnosis for thyroid cancer in Italy are among the highest worldwide. This study aimed to estimate population-based frequency and trends of thyroidectomies in Italy by type of surgical procedure (total/partial), indication (tumors/other conditions), sex, age, and geographical region. Materials and Methods: Age-standardized rates (ASRs) of thyroidectomies were estimated from 2001 to 2018 using the national hospital discharges database. Results: In Italy, ASRs of thyroidectomies were nearly 100 per 100,000 women in 2002-2004 and decreased to 71 per 100,000 women in 2018. No corresponding variation was shown in men (ASR 27 per 100,000 men) in the overall period. A more than twofold difference between Italian regions emerged in both sexes. The proportion of total thyroidectomies (on the sum of total and partial thyroidectomies) in the examined period increased from 78% to 86% in women and from 72% to 81% in men. Thyroidectomies for goiter and nonmalignant conditions decreased consistently throughout the period (from 81 per 100,000 women in 2002 to 49 in 2018 and from 22 to 16 per 100,000 men), while thyroidectomies for tumors increased until 2013-2014 up to 24 per 100,000 women (9 per 100,000 men) and remained essentially stable thereafter. Conclusions: The decrease in thyroidectomies for nonmalignant diseases since early 2000s in Italy may derive from the decrease of goiter prevalence, possibly as a consequence of the reduction of iodine deficiency and the adoption of conservative treatments. In a context of overdiagnosis of thyroid cancer, recent trends have suggested a decline in the diagnostic pressure with a decrease in geographic difference. Our results showed the need and also the possibility to implement more conservative surgical approaches to thyroid diseases, as recommended by international guidelines.

A pre-operative prognostic score for the selection of patients for salvage surgery after recurrent head and neck squamous cell carcinomas.

Salvage surgery in recurrent head and neck squamous cell carcinoma has a poor outcome, both in terms of survival and quality of life. Therefore, the identification of pre-operative prognostic factors to improve the selection of patients who could benefit the most from salvage surgery is clinically relevant. The present study is a single-center retrospective analysis of 164 patients treated with salvage surgery after recurrence of head and neck cancer. Progression free survival and overall survival were calculated through Kaplan-Meier method. Hazard risk (HR) and corresponding confidence intervals (CI) were estimated through Cox proportional hazard model, adjusting for potential confounders. Significant predictors were combined into a prognostic score, attributing one point to each factor. Progression-free survival and overall survival were respectively 50.3% and 56.5% at 2 years, and 36.6% and 44.2% at 5 years. Four pre-operative factors were independently associated with poor prognosis: age > 70 years (HR = 2.18; 95% CI 1.27-3.73), initial stage IV (HR = 2.37; 95% CI 1.18-4.76), disease free interval < 12 months (HR = 1.72; 95% CI 1.01-2.94), and loco-regional recurrence (HR = 2.22; 95% CI 1.22-4.04). No post operative factor was associated with oncologic outcomes. Patients with 3-4 unfavorable factors showed a 5-year overall survival of 0.0% compared to 65.7% in those with 0-1 unfavorable factors (HR = 5.61; 95% CI 2.89-10.92). Despite the low number of patients, 3-4 unfavorable factors were associated to worse prognosis in all sub-sites. In conclusion, age > 70 years, initial stage IV, disease-free interval < 12 months, and loco-regional recurrence are strong independent pre-operative predictors of poor outcome in patients undergoing salvage surgery. Patients with two or more of these factors should be informed about the low success rate after salvage surgery and alternative treatments should be considered.

Cetuximab in locally advanced head and neck squamous cell carcinoma: Biological mechanisms involved in efficacy, toxicity and resistance.

Since its introduction, the use of cetuximab in the treatment of head and neck squamous cell carcinoma (HNSCC) has experienced an evolution. Currently, cetuximab associated with radiotherapy is limited to the treatment of patients affected by a locally advanced malignancy and unfit for cisplatin. However, reliable biomarkers of cetuximab efficacy in this cancer setting are still lacking. This review focuses on the mechanisms of action of cetuximab, highlighting, in particular, the consequences of the binding to EGFR, and the pathways involved in the development of adverse events or acquired resistance. Indeed, adverse events, such as skin rash, have been associated with cetuximab efficacy in HNSCC several times. Acquired resistance is associated with microenvironment plasticity, which is, in turn, characterized by an increased immune infiltrate. The better definition of patients eligible for this kind of therapy could improve HNSCC management, possibly proposing a combined treatment with radiotherapy, cetuximab and immune checkpoint inhibitors as recently investigated.

Prognostic Nutritional Index Predicts Toxicity in Head and Neck Cancer Patients Treated with Definitive Radiotherapy in Association with Chemotherapy.

BACKGROUND: The Prognostic Nutritional Index (PNI) is a parameter of nutritional and inflammation status related to toxicity in cancer treatment. Since data for head and neck cancer are scanty, this study aims to investigate the association between PNI and acute and late toxicity for this malignancy. METHODS: A retrospective cohort of 179 head and neck cancer patients treated with definitive radiotherapy with induction/concurrent chemotherapy was followed-up (median follow-up: 38 months) for toxicity and vital status between 2010 and 2017. PNI was calculated according to Onodera formula and low/high PNI levels were defined according to median value. Odds ratio (OR) for acute toxicity were calculated through logistic regression model; hazard ratios (HR) for late toxicity and survival were calculated through the Cox proportional hazards model. RESULTS: median PNI was 50.0 (interquartile range: 45.5-53.5). Low PNI was associated with higher risk of weight loss > 10% during treatment (OR = 4.84, 95% CI: 1.73-13.53 for PNI < 50 versus PNI ≥ 50), which was in turn significantly associated with worse overall survival, and higher risk of late mucositis (HR = 1.84; 95% CI:1.09-3.12). PNI predicts acute weight loss >10% and late mucositis. CONCLUSIONS: PNI could help clinicians to identify patients undergoing radiotherapy who are at high risk of acute and late toxicity.

Organ preservation in locally advanced head and neck cancer of the larynx using induction chemotherapy followed by improved radiation schemes.

The present prospective study seeks to evaluate overall and disease free survival, response and organ preservation rate, and toxicity of an intensive chemotherapy regimen (CT) followed by unconventional radiotherapy (RT) in patients with locally advanced operable head and neck cancer. Between January 1998 and December 2006 (June 2005), 115 patients with locally advanced, operable head and neck cancer were evaluated. A total of 333 cycles of neoadjuvant CT (cisplatin-5FU, days 1, 14, 28) followed by hyperfractionated/accelerated radiotherapy were given to 108 patients. A total of 108 patients were evaluable and received the planned CT-RT treatment. Two months after the end of RT, 97.2% of patients had a clinical complete remission of the primary and 67.5% of the neck node site. The overall survival was 55% and cause-specific survival was 73% at 5 years. Of the 33 relapsed patients, 12 recurred only at the primary site and 10 patients had distant metastases. The overall organ preservation rate was 73.5%. The chemotherapy regimen reported an overall cardiotoxicity from 5FU in 14% of patients, with severe toxicity in 3%. The radiotherapy schedule developed 84% of Grade 3-4 mucositis in the observed patients. The accelerated CT-RT regimen is able to achieve a high rate of larynx preservation, a good tolerability, and a satisfactory cause-specific overall survival.

Safety Profiles and Pharmacovigilance Considerations for Recently Patented Anticancer Drugs: Advanced Thyroid Cancer.

BACKGROUND: Thyroid cancer is the most common endocrine neoplasia and represents approximately 1.5% to 2.1% of all cancers diagnosed annually worldwide. Iodine Refractory Differentiated Thyroid Carcinoma (RR-DTC) and advanced/metastatic medullary thyroid carcinoma are relatively uncommon yet prognostically significant thyroid cancers. Gene rearrangements resulting in the aberrant activity of tyrosine kinases have been identified as drivers of oncogenesis in a variety of cancers, including thyroid cancer. Many Multi-Kinase Inhibitors (MKIs) which are now FDA-/EMA approved for thyroid cancer have shown clinical benefit in patients with advanced cancer. Treatment related toxicities occur frequently with these drugs and can be severe or life-threatening. OBJECTIVES: This review summarizes the role of targeted therapy with MKIs in the management of RRDTC and advanced/metastatic MTC patients, focusing on side-effect profiles of these drugs, with a presentation of several recent patents published in this field. METHODS: We review the scientific literature on advanced thyroid cancer and analyze the International Pharmacovigilance database (FAERS, Eudravigilance, and WHO Vigibase) for adverse drug reactions. RESULTS: This systematic analysis highlights the difference in the safety profile of the recent drugs used in the treatment of advanced thyroid cancer and the recent discoveries for diagnosis or treatment of the thyroid cancer. CONCLUSION: It is essential to investigate the safety profile of recent anticancer drugs for advanced thyroid cancer to allow health professionals to make the best choice for each patient by conducting risk/benefit assessment.

Direct health-care cost of head and neck cancers: a population-based study in north-eastern Italy.

Improvements in prognosis of head-and-neck squamous cell carcinoma (HNSCC) have paralleled with an increase in health-care costs, so that an economic evaluation is of growing importance. Presently, most of the evidence is from insurance-based studies in the USA. Between 2007 and 2010, 879 HNSCC patients were identified through the population-based cancer registry of the Friuli Venezia Giulia region, including 266 oral, 187 oropharyngeal, 136 hypopharyngeal, and 290 laryngeal cancers. Health-care costs from diagnosis to treatment initiation and in the following 2 years were retrieved through a record linkage with the regional health data warehouse. This database collected comprehensive health information on all resident citizens. Generalized linear models with a gamma distribution and log-link function were applied to model costs. The average health-care cost from diagnosis up to 2 years after treatment initiation was €20,184 (95% confidence interval: €19,634 - 20,733). Heterogeneity emerged according to cancer site, elective treatment, and retreatment for cancer persistence/recurrence (no: €13,896; yes: €24,599; p < 0.001). An advanced stage was associated with increased costs stage (I: €12,969; II: €18,276; III: €26,229; IV: €25,574; p < 0.001) as the result of treatment complexity and elevated frequency of patients retreatment due to recurrence. These findings further support strategies to diagnose patients at an earlier cancer stage and the accurate definition of diagnostic and treatment pathways, to start treating patients when radical unimodal approach is still feasible. Besides the advantage in prognosis due to timely curative treatments, this would reduce the economic burden of cancer treatment.

Correction to: Unusual presentation of recurrent papillary thyroid microcarcinoma with neck muscles and skin dissemination.

The original version of this article unfortunately contained a mistake. The title of this article was rendered incorrectly; the correct title is as follows: Unusual presentation of recurrent papillary thyroid microcarcinoma with neck muscles and skin dissemination.

223Ra-chloride therapy in men with hormone-refractory prostate cancer and skeletal metastases: Real-world experience.

BACKGROUND: Radium-223 (223Ra) chloride, an alpha emitter, has been shown to improve overall survival (OS) and pain control, and to delay skeletal-related events, in patients with castration-resistant prostate cancer (CRPC) and bone metastases. Our retrospective observational study presents the first Italian experience on the efficacy and safety of 223Ra therapy in routine clinical practice. METHODS: A total of 83 patients with metastatic CRPC were treated with 223Ra at 3 Italian centers between August 2013 and August 2016. 223Ra-chloride (55 kBq/kg) was administered every 4 weeks for a total of 6 cycles. Primary endpoints were OS and progression-free survival (PFS). Secondary endpoints included toxicity, pain evaluation using numeric rating scale (NRS), symptomatic skeletal-related events and biomarkers response. RESULTS: Patients had a median age of 75 (range 53-89) years. The majority of men showed a Gleason score of 7, 8, or 9. Forty-one patients completed 6 treatment cycles; 33 stopped treatment before completing 6 cycles. Nine were still receiving therapy at the time of data collection. At the end of therapy, NRS pain scores significantly improved ( p < .000001). OS was a mean of 10.1 months, while median OS had not been attained. According to Kaplan-Meier estimation, OS and PFS were 17.5 and 7.7 months, respectively. There was a significant correlation between OS and PFS with the number of 223Ra cycles; patients receiving all 6 cycles experienced the major benefit from the therapy. 223Ra was well-tolerated. CONCLUSIONS: 223Ra alpha therapy is an important therapeutic option for men with CRPC and symptomatic skeletal metastases.

A new standardized data collection system for interdisciplinary thyroid cancer management: Thyroid COBRA.

The big data approach offers a powerful alternative to Evidence-based medicine. This approach could guide cancer management thanks to machine learning application to large-scale data. Aim of the Thyroid CoBRA (Consortium for Brachytherapy Data Analysis) project is to develop a standardized web data collection system, focused on thyroid cancer. The Metabolic Radiotherapy Working Group of Italian Association of Radiation Oncology (AIRO) endorsed the implementation of a consortium directed to thyroid cancer management and data collection. The agreement conditions, the ontology of the collected data and the related software services were defined by a multicentre ad hoc working-group (WG). Six Italian cancer centres were firstly started the project, defined and signed the Thyroid COBRA consortium agreement. Three data set tiers were identified: Registry, Procedures and Research. The COBRA-Storage System (C-SS) appeared to be not time-consuming and to be privacy respecting, as data can be extracted directly from the single centre's storage platforms through a secured connection that ensures reliable encryption of sensible data. Automatic data archiving could be directly performed from Image Hospital Storage System or the Radiotherapy Treatment Planning Systems. The C-SS architecture will allow "Cloud storage way" or "distributed learning" approaches for predictive model definition and further clinical decision support tools development. The development of the Thyroid COBRA data Storage System C-SS through a multicentre consortium approach appeared to be a feasible tool in the setup of complex and privacy saving data sharing system oriented to the management of thyroid cancer and in the near future every cancer type.

Malignant struma ovarii harboring a unique NRAS mutation: case report and review of the literature.

Struma ovarii (SO), a rare tumor containing at least 50% of thyroid tissue, represents approximately 5% of all ovarian teratomas; its malignant transformation rate is reported to occur in up to 10% of cases and metastases occur in about 5-6% of them. We describe a 36-year old woman who underwent laparoscopic left annessectomy two years earlier because of an ovarian cyst. Follow-up imaging revealed a right adnexal mass, ascitis and peritoneal nodes that were diagnosed as comprising a malignant SO with peritoneal secondary localizations at histopathology performed after intervention. Restaging with 18F-FDG-PET/CT scan, abdominal CT and ultrasonography showed abnormalities in the perihepatic region and presacral space and left hypochondrium localizations. The patient underwent thyroidectomy, hepatic nodulectomy and cytoreductive peritonectomy: histopathological examination did not show any malignant disease in the thyroid and confirmed the presence of peritoneal localizations due to malignant SO; molecular analysis detected NRAS Q61K mutation in exon 3, whereas no mutations were identified on the BRAF gene. The patient underwent radioiodine treatment: serum Tg was decreased at first follow-up after three months of 131I-therapy. We believe that our case raises some interesting considerations. First, pathologists should be aware of this entity and should check for the presence of point mutations suggesting an aggressive disease behavior, which could be beneficial for an optimal therapeutic approach. Second, although most of the knowledge in this field comes from case reports, efforts should be made to standardize the management of patients affected by malignant SO, including use of practice guidelines.

The impact of time to treatment initiation on survival from head and neck cancer in north-eastern Italy.

OBJECTIVES: To evaluate the impact of time to treatment initiation (TTI) on overall survival in patients with head-and-neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: In the period 2003-2009, 1616 HNSCC patients were diagnosed in Friuli Venezia Giulia Region, Northeastern Italy, including 462 oral, 346 oropharyngeal, 212 hypopharyngeal, and 596 laryngeal cancers. Clinical information, including date and type of first treatment, and follow-up were retrieved from the regional Cancer Registry and a population-based health database collecting comprehensive health information on people living in the Region. Multivariate hazard ratio (HR) and confidence intervals (CI) were calculated through Cox model. RESULTS: Overall, the median TTI was 28days, (Q1-Q3: 13-45days), but significant variations emerged according to anatomical site, cancer stage, treatment approach, and care transition to specialized centers. Five-year overall survival decreased with increasing treatment delay from 62% for TTI<30days to 39% for TTI≥90days (p<0.01). HR of death was 1.13 (95% CI: 0.92-1.39) for TTI between 45-89days, and 1.47 (1.05-2.05) for TTI≥90days. The association between TTI and poor prognosis was stronger for laryngeal cancers and early-stage HNSCCs. Further, care transition from community hospitals to specialized centers was associated to a better prognosis (HR=0.73; 95% CI: 0.60-0.88). CONCLUSION: Our study findings suggest that HNSCC patients treated within 45days from diagnosis have increased survival probabilities and that early-stage patients suffered the most from treatment delay. Furthermore, care transition to specialized centers -though competitive to timely treatment- improves survival by providing the most innovative technologies and treatment approaches.

External beam radiotherapy in thyroid carcinoma: clinical review and recommendations of the AIRO "Radioterapia Metabolica" Group.

The therapeutic approach to thyroid carcinoma usually involves surgery as initial treatment. The use of external beam radiotherapy (EBRT) is limited to high-risk patients and depends on clinical stage and histologic type. Different behavior patterns and degrees of aggressiveness of thyroid carcinomas require different management for differentiated, medullary, and anaplastic carcinoma. However, the role of EBRT is an issue of debate. Most clinical studies are retrospective and based on single-institution experiences. In this article, we review the main literature and give recommendations for the use of EBRT in thyroid carcinoma on behalf of the "Radioterapia Metabolica" Group of the Italian Radiation Oncology Association.

Thoracic radiation therapy and concomitant low-dose daily paclitaxel in non-small cell lung cancer: a phase I study.

The primary objective of the current study was to determine the maximum tolerated dose of paclitaxel (PTX) that could be added daily to radiation therapy (RT) in patients with non-small cell lung cancer (NSCLC). The secondary objective was to achieve a plasma concentration of PTX estimated to exert a radiosensitizing effect. Eighteen patients with locally advanced NSCLC were treated. 60 Gy of RT were given in 2 Gy fractions, 5 days per week. A daily dose of PTX was delivered by 4-h i.v. infusion before RT. The initial dose level of PTX was 9 mg/m2/day, escalated by 1 mg at each additional patient triplet. Two out of 6 patients experienced acute dose limiting toxicity (DLT) at the 12 mg/m2/day PTX dose level. PTX continuously greater than 10 nM, the estimated radiosensitizing condition, was achieved at the PTX dose level of 12 mg/m2/day. PTX at doses up to 11 mg/m2/day may be safely added to a conventional conformal RT course. Both DLT and the estimated radiosensitizing plasma exposure to PTX were encountered at the 12 mg/m(2)/day dose level.

Neoadjuvant accelerated chemotherapy followed by hyperfractionated radiation therapy in patients with operable, locally advanced head and neck carcinoma.

A prospective phase II trial was carried out to evaluate an accelerated chemotherapy (CT) regimen followed by hyperfractionated radiation therapy (RT) in previously untreated Stage III-IV, operable (total laryngectomy), head and neck cancer patients. The current study evaluates overall survival, loco-regional control, organ preservation rates and toxicity. Between April 1997 and December 2002, 68 patients with advanced head and neck cancer were treated with 3 cycles of induction CT (cisplatin and 5-fluorouracil; days 1, 14, and 28) followed by hyperfractionated RT (7440 cGy/62 fractions). Sixty patients received the planned RT-CT treatment. Two months after the end of RT, 96% of patients had a clinical complete remission of the primary and 66% of the neck disease. At a median follow-up of 32 months, the 3-year overall and disease-free survival rates were 66% and 76%, respectively. Seven patients recurred on the primary site, 1 on the neck and 2 patients only had distant metastases. The organ preservation rate was 73%. Acute grade 3-4 mucositis occurred in 75% of patients and an 18% rate of CT-related cardiotoxicity was reported. The accelerated CT-RT regimen achieves a high rate of larynx preservation albeit with considerable toxicity. The current prospective clinical trial was approved by the Ethics Committee of the Centro di Riferimento Oncologico (C.R.O.) on May 27, 1996, # CRO-02-96. Written informed consent was required from all patients entering the study.