Patterns of Care for Breast Radiotherapy in Italy: Breast IRRadiATA (Italian Repository of Radiotherapy dATA) Feasibility Study.

Aim. Breast IRRADIATA (Italian Repository of RADIotherapy dATA) is a collaborative nationwide project supported by the Italian Society of Radiotherapy and Clinical Oncology (AIRO) and the Italian League Against Cancer (LILT). It focuses on breast cancer (BC) patients treated with radiotherapy (RT) and was developed to create a national registry and define the patterns of care in Italy. A dedicated tool for data collection was created and pilot tested. The results of this feasibility study are reported here. Methods. To validate the applicability of a user-friendly data collection tool, a feasibility study involving 17 Italian Radiation Oncology Centers was conducted from July to October 2021, generating a data repository of 335 BC patients treated between January and March 2020, with a minimum follow-up time of 6 months. A snapshot of the clinical presentation, treatment modalities and radiotherapy toxicity in these patients was obtained. A Data Entry Survey and a Satisfaction Questionnaire were also sent to all participants. Results. All institutions completed the pilot study. Regarding the Data Entry survey, all questions achieved 100% of responses and no participant reported spending more than 10 min time for either the first data entry or for the updating of follow-up. Results from the Satisfaction Questionnaire revealed that the project was described as excellent by 14 centers (82.3%) and good by 3 (17.7%). Conclusion. Current knowledge for the treatment of high-prevalence diseases, such as BC, has evolved toward patient-centered medicine, evidence-based care and real-world evidence (RWE), which means evidence obtained from real-world data (RWD). To this aim, Breast IRRADIATA was developed as a simple tool to probe the current pattern of RT care in Italy. The pilot feasibility of IRRADIATA encourages a larger application of this tool nationwide and opens the way to the assessment of the pattern of care radiotherapy directed to other cancers.

Application of a non-pharmacological technique in addition to the pharmacological protocol for the management of children's preoperative anxiety: A 10 years' experience.

The aim of the study was to investigate how Non- Pharmacological Techniques (NPT), in addition to standard pharmacological techniques, can help to manage and reduce the preoperative anxiety of children waiting for Day Surgery procedures (DS). Isola Serena activity started in 2008 to manage the preoperative time of children waiting for surgery in the playing room. The latter is run by a pedagogist. NPT includes use of games and toys, readings and drawings. A descriptive and comparative study was conducted on 50 children, aged 4 to 12 years, randomly assigned to Isola Serena group ISG and control group CG. All children received standard pharmacological techniques, while those of the ISG also received the NPT. The evaluation of the preoperative anxiety level (modified Yale Preoperative Anxiety Scale) and parent's coping style (Coping Inventory for Stressful Situation) compared the two groups. The ISG showed a significantly lower level of preoperative anxiety than the CG. Parents' coping style was not related to the preoperative anxiety. The activity performed in the Isola Serena Project resulted to be effective for the reduction of preoperative anxiety in children undergoing DS procedures.

Radiotherapy activities and technological equipment in Veneto, Italy: a report from the Rete Radioterapica Veneta.

BACKGROUND: Despite the pivotal role of radiotherapy in oncology, the provision of radiation treatments remains inadequate in many areas of the world. The present report is an assessment conducted among Radiation Oncology centers of Veneto region with the aim to collect information concerning radiotherapy assets and technological equipment availability. METHODS: Data concerning Veneto Radiation Oncology departments about radiotherapy activities, number of treatments, techniques used and radiotherapy machines available were collected. The reference time period was 2018. Reimbursement system databases and business intelligence systems were used. Extra-regional attraction and migration were evaluated. When available, data were compared to previous years. RESULTS: Veneto in 2018 was endowed with 1 megavolt unit for about 153,000 inhabitants. The number of megavolt machines per million inhabitants resulted to be 6.72. In 51% of radiotherapy treatments, intensity-modulated techniques were performed. Six percent of treatments were administered to extra-regional patients. CONCLUSION: Radiotherapy assets and equipment in Veneto seem to be appropriate to standard requests in terms of availability and technology.

Pretreatment High MCV as Adverse Prognostic Marker in Nonanemic Patients with Head and Neck Cancer.

OBJECTIVE: Mean corpuscular volume (MCV) has been shown in to be a reliable prognostic marker in other cancers; however, no evidence exists on its use in head and neck squamous cell carcinoma (HNSCC). This study aimed to investigate the association between MCV, hemoglobin, platelet count and albumin concentration, and survival in stage III/IVA-B HNSCC treated with concurrent chemoradiotherapy. STUDY DESIGN: Retrospective cohort study. METHODS: In this multicenter retrospective study, we analyzed MCV, platelet count, hemoglobin concentration, and albumin concentration in peripheral blood samples from 260 patients with HNSCC undergoing organ preservation treatment with curative intent at the time of diagnosis. We then analyzed survival outcomes after accounting for confounders using multivariate analysis. RESULTS: After adjustment for potential confounders, patients with low hemoglobin had a 3.3-fold higher risk of death (95% confidence interval [CI]: 2.26-4.81) than those with normal hemoglobin. Patients with an elevated MCV had a 1.54-fold higher risk of death (95% CI: 1.06-2.24), independent of site, stage, and human papillomavirus status. Interestingly, the effect of MCV on overall and progression-free survival was limited to those with a normal pretreatment hemoglobin. We identified no associations between pretreatment platelet count or albumin concentration and survival. CONCLUSION: These findings suggest that pretreatment anemia and macrocytosis are independent predictors of lower overall and progression-free survival in HNSCC patients undergoing organ preservation treatment. LEVEL OF EVIDENCE: III Laryngoscope, 131:E836-E843, 2021.

Dermopigmentation of the nipple-areola complex in a dedicated breast cancer centre, following the Treviso Hospital (Italy) LILT model.

BACKGROUND: Dermopigmentation, also known as medical tattooing, is a complementary technique in the reconstruction of the nipple-areola and an adjuvant procedure to improve colour mismatch. In 2009, tattooing of the nipple-areola complex (NAC) was introduced by Treviso Hospital through a project conducted in cooperation with the local section of the Italian Anti-Cancer League (LILT). METHODS: From 2010 to 2016, 169 patients treated for breast cancer underwent dermopigmentation treatments. Patients were selected by the hospital plastic and breast surgeons. Dermopigmentation was performed at the LILT (Lega Italiana per la Lotta contro i Tumori, Italian Cancer League) facility following a specific procedure to ensure safety. A sterile disposable surgical set was used. RESULTS: Of 169 patients treated in 309 treatment sessions, no serious complications were reported after tattooing, with only three cases seen of minor complications. Patients expressed a high level of satisfaction (90%) with the aesthetic results. CONCLUSION: The study found that dermopigmentation of the NAC is a safe approach, providing benefits both to the patients and the hospital itself. Medical tattooing of the NAC is a simple and safe nonsurgical technique that reduces missed workdays and increases the time available for other commitments. This ultimately translates into savings for society and the healthcare system.

Dysphagia in head and neck cancer patients treated with radiotherapy and systemic therapies: Literature review and consensus.

BACKGROUND: Head and neck cancer (HNC) and its therapy are associated with acute and late swallowing dysfunction. Consensus guidelines regarding evaluation and management are lacking. To address this gap, a multidisciplinary team of experts (oncologists, practitioners, deglutologists, etc.) met in Milan 17-18 February 2013 with the aim of reaching a consensus on the management of swallowing difficulties in HNC patients treated with radiotherapy with or without systemic therapies (such as chemotherapy and targeted agents). The consensus was focused particularly on those statements with limited evidence. The results of the literature review and the statements that obtained a consensus are reported and discussed in this paper. MATERIALS AND METHODS: The Delphi Appropriateness Method was used for this consensus. External expert reviewers then evaluated the conclusions carefully according to their area of expertise. RESULTS: This paper contains 6 clusters of statements about the management of swallowing problems in radio-treated HNC patients and a review of the recent literature on these topics. CONCLUSIONS: Dysphagia assessment and its management are difficult and require a multi-team cooperation (ENT specialists, radiation and medical oncologists, deglutologists, etc.).

Non-endemic locoregionally advanced nasopharyngeal carcinoma: long-term outcome after induction plus concurrent chemoradiotherapy in everyday clinical practice.

The aim of this study was to evaluate the long-term outcome in Caucasian population of a non-endemic area treated for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) with multidrug platinum-based induction plus concurrent chemoradiotherapy (IC/CCRT) in everyday clinical practice setting. Between May 1990 and July 2007, 75 patients with newly diagnosed histologically confirmed LA-NPC were given IC/CCRT. All patients were judged suitable to receive conventional fractionated course of radiotherapy to a dose of 70 Gy in 35 fractions (2 Gy per fraction). The intended chemotherapy regimen consisted in one cycle of induction chemotherapy followed by radiotherapy concomitantly with two cycles of chemotherapy. Each cycle of chemotherapy included cis-platinum, 100 mg/m(2), and continuous infusion of 5-fluorouracil, 1,000 mg/m(2)/d for 5 days. The median follow-up in survivors was 122 months. The complete response rate after CCRT was 90.7%. The main limiting toxicity was grade 3 and 4 pharyngeal mucositis (46.7%). Five-year cumulative rate of locoregional control (LRC), distant control (DC), overall survival (OS), and event-free survival (EFS) was 80.1, 82.2, 72.0, and 66.7%, respectively. Ten-year cumulative rate of LRC, DC, OS, and EFS was 73.4, 73.8, 57.1, and 55.2%, respectively. At multivariate analysis advanced N category and low hemoglobin levels at baseline were found to be independent predictors for both worse OS and EFS. In everyday clinical practice, treating LA-NPC with cisplatin-based IC/CCRT was relatively safe and long-term effective.

Is neck dissection necessary after induction plus concurrent chemoradiotherapy in complete responder head and neck cancer patients with pretherapy advanced nodal disease?

BACKGROUND: The aim of the present study was to assess, in the setting of a single-institution prospective clinical trial, the necessity of planned neck dissection (PND) in physically and radiologically complete responders with pretherapy advanced nodal disease. METHODS: Between January 2000 and July 2007 a total of 139 patients were enrolled to receive a regimen of platinum-based multidrug induction-concurrent chemoradiotherapy (IC/CCRT). A total of 75 of the enrolled patients with advanced nodal disease were included in this retrospective study. Between 8 and 12 weeks from the end of treatment, the response to IC/CCRT was evaluated by fiber-optic endoscopy and head and neck contrast-enhanced computed tomography or magnetic resonance imaging. RESULTS: The complete clinical response (cCR) rate was 68%. Among the 51 patients who achieved locoregional cCR at the end of CCRT, 8 underwent PND according to the study recommendation. Of the 43 patients with cCR who did not undergo PND, 2 patients (4.7%) experienced isolated regional recurrences with the 5-year regional control being 82%. Patients with cCR did not have a significantly lower regional control compared with patients with cCR who underwent ND (P=.962). Pathological evidence of residual disease was found in 81% of the patients with less than cCR who underwent ND. CONCLUSIONS: In physically and radiologically complete responders to IC/CCRT, a PND appears not justified. Conversely, PND should be performed in patients clinically suspected of having residual disease in the neck, as a significant proportion have viable tumor cell in post CCRT ND.

Functional organ preservation after chemoradiotherapy in elderly patients with loco-regionally advanced head and neck squamous cell carcinoma.

The aim of the present investigation is to evaluate the outcome after induction chemotherapy and concurrent multi-drug chemoradiotherapy (IC/CCRT) with or without post-chemoradiation neck dissection in medically fit elderly patients with loco-regionally advanced head and neck squamous cell carcinoma (HNSCC). Retrospective study including 44 elderly patients (median age 71 years; range 66-77 years) with previously untreated, inoperable, histologically proven non-metastatic stage III or IV HNSCC. Following one cycle of IC, two cycles of cis-platinum and 5-fluorouracil CCRT with conventional fractionated radiotherapy up to a dose of 66-70 Gy were administrated. A neck dissection was recommended for patients with node metastasis larger than 3 cm regardless of the response to therapy and for patients who had suspected persistent neck disease 8-12 weeks after completing treatment. Salvage surgery was considered for histologically proven persistent or recurrent tumor in the primary site. Time-to-event data were described using Kaplan-Meier actuarial curves. Overall, 37 patients (84.1%) completed the planned treatment. There were no cases of treatment-related deaths. Twenty-nine patients (65.9%) developed severe toxicities with grade 4 toxicity accounting for 22.7%. The median follow-up time in survivors was 41 months. Three-year overall survival, progression-free survival, and functional progression-free survival estimates were 70.9, 67.0, and 57.3%, respectively. In selected medically fit elderly patients with loco-regionally advanced HNSCC, cis-platinum-based chemoradiotherapy can be successfully applied, with moderate adverse events, in attempt to preserve a functional upper aerodigestive tract.

Matched survival analysis in patients with locoregionally advanced resectable oropharyngeal carcinoma: platinum-based induction and concurrent chemoradiotherapy versus primary surgical resection.

PURPOSE: The outcome of a prospective case series of 47 patients with newly diagnosed resectable locoregionally advanced oropharyngeal squamous cell carcinoma treated with platinum-based induction-concurrent chemoradiotherapy (IC/CCRT) was compared with the outcome of 47 matched historical control patients treated with surgery and postoperative RT. METHODS AND MATERIALS: A total of 47 control patients with locoregionally advanced oropharyngeal squamous cell carcinoma were identified from review of a prospectively compiled comprehensive computerized head-and-neck cancer database and were matched with a prospective case series of patients undergoing IC/CCRT by disease stage, nodal status, gender, and age (± 5 years). The IC/CCRT regimen consisted of one cycle of induction chemotherapy followed by conventionally fractionated RT to a total dose of 66-70 Gy concomitantly with two cycles of chemotherapy. Each cycle of chemotherapy consisted of cisplatinum, 100 mg/m(2), and a continuous infusion of 5-fluorouracil, 1,000 mg/m(2)/d for 5 days. The survival analysis was performed using Kaplan-Meier estimates. Matched-pair survival was compared using the Cox proportional hazards model. RESULTS: No significant difference was found in the overall survival or progression-free survival rates between the two groups. The matched analysis of survival did not show a statistically significant greater hazard ratio for overall death (hazard ratio, 1.35; 95% confidence interval, 0.65-2.80; p = .415) or progression (hazard ratio, 1.44; 95% confidence interval, 0.72-2.87; p = .301) for patients undergoing IC/CCRT. CONCLUSION: Although the sample size was small and not randomized, this matched-pair comparison between a prospective case series and a historical cohort treated at the same institution showed that the efficacy of IC/CCRT with salvage surgery is as good as primary surgical resection and postoperative RT.

Early nutritional intervention improves treatment tolerance and outcomes in head and neck cancer patients undergoing concurrent chemoradiotherapy.

GOALS OF WORK: Patients with head and neck cancer (HNC) undergoing chemoradiotherapy are at high risk of malnutrition, which is related to complication rate. The aim of this study was to investigate the impact of an early intensive nutritional intervention on nutritional status and outcomes in patients undergoing chemoradiotherapy for HNC. MATERIALS AND METHODS: We analysed retrospectively the clinical documentation of 33 HNC patients who were referred for early nutritional intervention (nutrition intervention group, NG) before they were submitted to chemoradiotherapy. The outcome of these patients was compared to that of 33 patients who received chemoradiotherapy without receiving a specifically designed early nutrition support programme (control group, CG). MAIN RESULTS: NG patients lost less weight during chemoradiotherapy compared to CG patients (-4.6 +/- 4.1% vs -8.1 +/- 4.8% of pre-treatment weight, p < 0.01, at the completion of treatment). Patients in the NG experienced fewer radiotherapy breaks (>5 days) for toxicity (30.3% vs 63.6%, p < 0.01); the mean number of days of radiation delayed for toxicity was 4.4 +/- 5.2 in NG vs 7.6 +/- 6.5 in CG (p < 0.05); a linear correlation was found between percentage of weight lost from baseline to chemoradiotherapy completion and days of radiation delays (p < 0.01). There were less patients who had an unplanned hospitalisation in the NG relative to the CG (16.1% vs 41.4%, p = 0.03). In the NG, symptoms having an effect on the nutritional status developed early and were present in the nearly totality of patients at chemotherapy completion; 60.6% of NG patients needed tube feeding. CONCLUSIONS: Early nutrition intervention in patients with HNC receiving chemoradiotherapy resulted in an improved treatment tolerance and fewer admissions to hospital. This result suggests that nutritional intervention must be initiated before chemoradiotherapy, and it needs to be continued after treatment completion.

Long-term quality of life after treatment for locally advanced oropharyngeal carcinoma: surgery and postoperative radiotherapy versus concurrent chemoradiation.

The aim of this study was to evaluate the long-term quality of life (QoL) in survivors with oropharyngeal carcinoma (OC) treated with surgery and postoperative radiotherapy (PORT) versus concurrent chemoradiation (CRT) using the European Organization for Research and Treatment of Cancer QoL Questionnaires. The study group consisted of 57 patients. The scores for physical (P=0.043) and social (P=0.036) functioning were significantly more favorable in the chemoradiation group. Surgical patients showed statistically higher problems with fatigue (P=0.047), pain (P=0.027), swallowing (P=0.042), social eating (P=0.038) and social contact (P=0.002). CRT group reported significantly greater problems with teeth (P=0.049), open mouth (P=0.036), dry mouth (P=0.022) and sticky saliva (P=0.044). The global QoL score was higher in CRT group (P=0.027). These results support an organ preservation approach with CRT in patients with advanced OC. However, considering the absence of randomized trial comparing outcomes after surgical versus nonsurgical approaches, severe xerostomia following CRT, the higher postoperative morbidity in the setting of salvage surgery, future prospective clinical trials on greater samples of patients are needed to confirm our conclusions.

Long-term quality of life after total laryngectomy and postoperative radiotherapy versus concurrent chemoradiotherapy for laryngeal preservation.

OBJECTIVE: To compare the quality of life (QoL) of patients who underwent total laryngectomy with voice prosthesis insertion and postoperative radiotherapy (PORT) with those receiving concurrent chemoradiation for laryngeal preservation. STUDY DESIGN: Retrospective, cross-sectional study in a tertiary academic center. METHODS: The European Organization for Research and Treatment of Cancer Quality of Life Questionnaires were used to assess long-term QoL in 67 patients treated for laryngeal cancer. RESULTS: The scores of functional scales for physical (P < .000), social (P = .001), and role functioning (P = .043) were more favorable in the chemoradiation group. The global QoL score was higher in the nonsurgical group (P = .016). Surgical patients reported on sleep disturbance (P < .000), dyspnea (P = .001), and pain (P = .003), with a higher scores and greater difficulties with the senses (P < .000), social contact (P = .002) and speech (P = .010). The chemoradiation group reported greater problems with dry mouth (P < .000) and sticky saliva (P = .005). CONCLUSION: We found better long-term QoL scores in patients undergoing concurrent chemoradiation. This appears to be mainly because of better physical functioning, social functioning, and social contact and smaller problems with pain, respiration, speech, the senses, and sleep disturbances.

The impact of radiotherapy and GERD on in situ lifetime of indwelling voice prostheses.

The aim of this study was (1) to analyze the in situ lifetime of indwelling voice prostheses (VPs) and (2) to investigate the role of some variables on device lifetime. We conducted a retrospective clinical study of patients visiting our outpatient clinic for problems related to their VP from August 1998 to March 2006. The mean in situ VP lifetime was 180.9 days (95% CI 162.6-199.2). The mean in situ VP lifetime was 163.3 and 202.9 days in patients irradiated and not irradiated, respectively (P = 0.008). The mean in situ VP lifetime was 126.5 and 215.7 days in patients with and without endoscopic evidence of erosive-ulcerative gastroesophageal reflux disease (GERD), respectively (P < 0.001). Multivariate analysis confirmed that radiotherapy and presence of GERD significantly affected the in situ VP lifetime. This study confirmed the relationship between short VP lifetime and radiation therapy. In addition, a possible association between GERD and limited device lifetime was identified.

Carcinoma metastatic to cervical lymph nodes from an occult primary tumor: the outcome after combined-modality therapy.

BACKGROUND: The aim of this retrospective analysis was to analyze the results of treatment of patients with cervical node metastases from carcinoma of occult primary with a policy including neck dissection and postoperative comprehensive radiotherapy. METHODS: Ninety patients were treated with curative intent from 1990 to 2002. RESULTS: The actuarial rate of neck disease control was 68.8% at 5 years (95% confidence interval [CI], 58.9%-78.7%). On multivariate analysis, the rate of neck disease control was significantly related to lymph nodal metastatic level (P = .006). The actuarial rate of developing head and neck primary tumors at 5 years was 8.9% (95% CI, 2.6%-15.2%). The 5-year actuarial rate of distant metastases was 19.1% (95% CI, 9.4%-28.9%). In multivariate analysis, a statistically significant difference in the rate of distant metastasis was obtained when patients were stratified according to the level of nodal involvement (P = .01) and the presence of extracapsular extension (P = .013). At the time of analysis, 50 of the 90 patients were alive. A total of 32 (35.6%) had died from causes related to their primary disease. Actuarial disease-specific survival at 2 and 5 years was 73.6% (95% CI, 64.3%-82.9%) and 62.8% (95% CI, 51.9%-73.7%), respectively. In multivariate analysis, a statistically significant difference in disease-specific survival was obtained when patients were stratified according to the level of nodal involvement and the presence of extracapsular extension. CONCLUSIONS: Our study seems to support the use of combined-modality therapy in patients with neck metastases from carcinoma of occult primary. However, in the absence of randomized trials, comprehensive irradiation cannot be routinely advised.

Long-term results of conventional radiotherapy versus accelerated hyperfractionated radiotherapy versus concomitant radiotherapy and chemotherapy in locoregionally advanced carcinoma of the oropharynx.

AIMS AND BACKGROUND: To compare conventional fractionation (CF) radiation therapy (RT), arm A, versus a split-course accelerated hyperfractionated schedule (S-AHF), arm B, versus CFRT plus concomitant chemotherapy (CT), arm C, in terms of five-year survival and toxicity for squamous cell tumors of the oropharynx. METHODS AND STUDY DESIGN: Between January 1993 and June 1998, 192 previously untreated patients with stage III and IV oropharyngeal carcinoma (excluding T1N1 and T2N1) were enrolled in a multicenter randomized phase III trial (ORO 93-01). In arms A and C, 66 to 70 Gy in 33 to 35 fractions was administered five days a week for six and a half to seven weeks. In arm B, the dose delivered was 64 to 67.2 Gy in two fractions of 1.6 Gy every day, five days a week, with a planned two-week split at 38.4 Gy. In arm C the CT regimen consisted of three cycles of carboplatin and 5-fluorouracil (CBDCA 75 mg/m2 on days 1 to 4 and 5-FU 1000 mg/m2 i.v. on days 1 to 4 every 28 days). RESULTS: No statistically significant difference was found in five-year overall survival (P = 0.39): 21% for arm A, 21% for arm B, and 40% for arm C. Similarly, there was no statistically significant difference in terms of five-year relapse-free survival: 15% for arm A, 17% for arm B, and 36% for arm C. There was a slight trend towards better five-year locoregional control (P = 0.07) for the combined arm: patients without locoregional relapse were 48% in arm C, 21% in arm A and 18% in arm B. Locoregional control was significantly better when arm C was compared with arms A and B combined (P = 0.02; arm A+B 20%; arm C 48%). Distant metastases were fairly balanced in the three arms (A: 14; B: 9; C: 11), with a tendency towards more frequent isolated distant metastasis development in arm C (8 of 11 [72%] versus 7 of 23 [30%] in arms A+B). Five-year second-tumor-free survival was 85%. The 13 second tumors were equally distributed and were mainly correlated with tobacco and alcohol consumption (five lung, two esophagus, two oral cavity, one larynx, one pancreas, one hepatocarcinoma, one myeloma). Arm C showed slightly more G3+ late side effects involving subcutaneous tissues and mucosa, although significant late sequelae were relatively uncommon and the mucosal side effects were mostly transient. The occurrence of persistent G3 xerostomia was comparable in the three treatment arms. CONCLUSIONS: The results obtained with the combination of CT and RT compared with RT alone did not reach statistical significance, but combined treatment almost doubled the five-year overall survival, relapse-free survival and locoregional control rate. Patients with advanced squamous cell carcinomas of the oropharynx who are medically suitable for the combined approach should be treated with a combination of radiotherapy and chemotherapy. The occurrence of second tumors is relatively common in these patients and may contribute substantially to the causes of death.

Cervical lymph node metastases from occult squamous cell carcinoma: analysis of 82 cases.

PURPOSE: The aim of this study was to analyze the prognostic value of some clinical factors and to compare the survival of different treatment plans in patients with cervical lymph node metastases from occult squamous cell carcinoma (SCC). METHODS: A retrospective review was conducted of patients who were diagnosed as having cervical lymph node metastases from occult SCC. Overall cumulative survival was analyzed using the standard Kaplan-Meier method. Tests of significance were based on log-rank statistics. RESULTS: The 82 patients in the study consisted of 69 males (84.2%) and 13 females (15.8%). The average age at diagnosis was 64.7 years. Fifty patients (60.9%) underwent surgical treatment of cervical metastasis. Radiotherapy was performed in 79 patients. Thirty-two patients (40.5%) received primary fractioned external beam radiotherapy; 47 patients (59.5%) received postoperative fractioned external beam radiotherapy. Ipsilateral radiotherapy was performed on 37 patients (46.8%), bilateral neck plus mucosal irradiation was performed in 42 patients (53.2%). Ten patients (12.2%) developed a primary tumor during the follow-up. The actuarial survival rates of all patients 2, 5 and 10 years after diagnosis were 50.9, 25.3 and 18.5%, respectively. Patients with nodal stage N2b, N2c and N3 had a significantly poorer prognosis than those with nodal stage N1 and N2a (p = 0.0239). The survival in patients with metastatic nodes in the supraclavicular region (level IV) was significantly poorer than that of patients with involvement of the upper-middle jugular lymph nodes (p = 0.0003). We observed a statistically significant better survival in patients receiving bilateral neck plus mucosal irradiation (p = 0.0003). CONCLUSIONS: Initial N-category and metastasis localization were the most important prognostic factors and nodal relapse the major cause of treatment failure, thus optimal management of cervical nodes appears crucial for the success of treatment. Patients receiving bilateral neck plus mucosal irradiation had a higher survival rate than those who received ipsilateral irradiation.

Randomized phase III trial of neoadjuvant chemotherapy in head and neck cancer: 10-year follow-up.

In 1986, we initiated a multicenter, randomized trial to compare induction chemotherapy with cisplatin and 5-fluorouracil followed by locoregional treatment (surgery and radiotherapy or radiotherapy alone) with locoregional treatment alone in patients with head and neck squamous cell carcinoma. Here we report the long-term results of the trial. A total of 237 patients with nonmetastatic stage III or IV head and neck carcinoma were randomly assigned to receive four cycles of neoadjuvant chemotherapy followed by locoregional treatment (group A) or locoregional treatment alone (group B). Among all patients, overall survival at 5 and 10 years was 23% (95% confidence interval [CI] = 15.3% to 30.9%) and 19% (95% CI = 11.6% to 26.4%), respectively, for those in group A and 16% (95% CI = 9.6% to 23.4%) and 9% (95% CI = 3.5% to 14.7%), respectively, for those in group B (P = .13). Among operable patients, we observed no difference between group A and group B in overall survival at 5 and 10 years (group A, 31% [95% CI = 14.9% to 47.3%] and 22.7% [95% CI = 7.1% to 38.3%], respectively; group B, 43.3% [95% CI = 25.6% to 61.0%] and 14.2% [95% CI = 0.1% to 28.3%], respectively; P = .73). Among inoperable patients, overall survival at 5 and 10 years was 21% (95% CI = 12.3% to 30.1%) and 16% (95% CI = 7.7% to 23.9%), respectively, for group A and 8% (95% CI = 1.5% to 12.3%) and 6% (95% CI = 0.1% to 9.1%), respectively, for group B (log-rank P = .04). Four cycles of neoadjuvant chemotherapy is a promising approach for treating patients with inoperable advanced head and neck cancer but not for treating patients with operable disease.

Locoregionally advanced carcinoma of the oropharynx: conventional radiotherapy vs. accelerated hyperfractionated radiotherapy vs. concomitant radiotherapy and chemotherapy--a multicenter randomized trial.

PURPOSE: To compare conventional fractionation radiation therapy (RT), Arm A, vs. split-course accelerated hyperfractionated RT (S-AHF), Arm B, vs. conventional fractionation RT plus concomitant chemotherapy (CT), Arm C, in terms of survival and toxicity for advanced, unresectable epidermoid tumors of oropharynx. METHODS AND MATERIALS: Between January 1993 and June 1998, 192 previously untreated patients affected with Stage III and IV oropharyngeal carcinoma (excluding T1N1 and T2N1) were accrued in a multicenter, randomized Phase III trial (ORO 93-01). For Arms A and C, 66-70 Gy in 33-35 fractions, 5 days a week, were administered in 6.5-7 weeks to tumor and positive nodes. In Arm B, the dose delivered to tumor and involved nodes was 64-67.2 Gy, giving 2 fractions of 1.6 Gy every day with an interfraction interval of at least 4 h and preferably 6 h, 5 days a week. At 38.4 Gy, a 2-week split was planned; after the split, RT was resumed with the same modality. In Arm C, CT regimen consisted of carboplatin and 5-fluorouracil (CBDCA 75 mg/m(2), Days 1-4; 5-FU 1,000 mg/m(2) i.v. over 96 h, Days 1-4, recycling every 28 days (at 1st, 5th, and 9th week). RESULTS: No statistically significant difference was detected in overall survival (p = 0.129): 40% Arm A vs. 37% Arm B vs. 51% Arm C were alive at 24 months. Similarly, there was no statistically significant difference in terms of event-free survival (p = 0.196): 20% for Arm A, 19% for Arm B, and 37% for Arm C were event free at 24 months. On the contrary, the 2-year disease-free survival was significantly different among the three arms (p = 0.022), with a superiority for Arm C. At 24 months, the proportion of patients without relapse was 42% for Arm C vs. 23% for Arm A and 20% for Arm B. Patients in Arm A less frequently developed G3+ acute mucositis than their counterparts in Arm B or C (14.7% vs. 40.3% vs. 44%). Regarding the CT-related acute toxicity, apart from 1 case of fatal nephrotoxicity, only hematologic G3+ (Grade 3 or higher) acute sequelae were observed (World Health Organization scale), most commonly leukopenia (22.7%). Arm C showed slightly more G3+ skin, s.c. tissue, and mucosal late side effects (RTOG scale), although significant sequelae were relatively uncommon, and mucosal sequelae were most commonly transient. The occurrence of persistent G3 xerostomia was comparable in all three treatment arms. CONCLUSIONS: The combination of simultaneous CT and RT with the regimen of this trial is better than RT alone in advanced oropharyngeal squamous-cell carcinomas, by increasing disease-free survival. This improvement, however, did not translate into an overall survival improvement, and was associated with a higher incidence of acute morbidity.