Xerostomia Quality of Life Scale (XeQoLS) questionnaire: validation of Italian version in head and neck cancer patients.

AIM: To translate the Xerostomia Quality-of-Life Scale (XeQoLS) into Italian language (XeQoLS-IT). Xerostomia is the most relevant acute and late toxicity in patients with head and neck cancer treated with radiotherapy (RT). Patient-reported outcome (PRO) instruments are subjective report on patient perception of health status. The XeQoLS consists of 15 items and measures the impact of salivary gland dysfunction and xerostomia on the four major domains of oral health-related QoL. METHODS: The XeQoLS-IT was created through a linguistic validation multi-step process: forward translation (TF), backward translation (TB) and administration of the questionnaire to 35 Italian patients with head and neck cancer. Translation was independently carried out by two radiation oncologists who were Italian native speakers. The two versions were compared and adapted to obtain a reconciled version, version 1 (V1). V1 was translated back into English by an Italian pro skilled in teaching English. After review of discrepancies and choice of the most appropriate wording for clarity and similarity to the original, version 2 (V2) was reached by consensus. To evaluate version 2, patients completed the XeQoLS-IT questionnaire and also underwent a cognitive debriefing. RESULTS: The questionnaire was considered simple by the patients. The clarity of the instructions and the easiness to answer questions had a mean value of 4.5 (± 0.71) on a scale from 1 to 5. CONCLUSION: A valid multi-step process led to the creation of the final version of the XeQoLS-IT, a suitable instrument for the perception of xerostomia in patients treated with RT.

Late toxicity, evolving radiotherapy techniques, and quality of life in nasopharyngeal carcinoma.

PURPOSE: To analyze quality of life (QoL) and functional state (FS) by patient-reported outcome (PRO) questionnaires (FACT-G, FACT-NP, PSS-HN, XeQOLS, and EQ-5D-3L) in long-term survivors nasopharyngeal carcinoma (NPC) treated with conventional radiotherapy (RT) and intensity modulated radiotherapy (IMRT). METHODS: 25 patients answered to five questionnaires about QoL and FS. All patients were assessed also for late toxicity. RESULTS: Functional Assessment of Cancer Therapy-General (FACT-G) and Performance Status Scale Head and Neck (PSS-HN) scores were significantly elevated (better QoL) in age <50 years (p = 0.03). PSS-HN score was higher in IMRT group. The observed xerostomia was lower in the IMRT group and in patients who received conventional RT had worse QoL according to XeQOLS (University of Michigan Xerostomia-Related Quality of Life Scale) score questionnaire. Lower PSS-HN score and higher XeQOLS score were significantly related with the late xerostomia (p = 0.009 and 0.002, respectively). CONCLUSIONS: Our preliminary data suggest that age, older techniques, xerostomia, and hearing loss are negative predictors of QoL.

Stereotactic body radiotherapy for cardiac and paracardiac metastases: University of Florence experience.

PURPOSE: This study sought to evaluate acute toxicity and local control in patients who underwent extracranial stereotactic body radiation therapy (SBRT) for paracardiac and cardiac metastatic lesions, defined as such when located at a maximum distance of 1 cm from the heart or inside its parenchyma. MATERIALS AND METHODS: Between January 2009 and May 2011, 16 patients with paracardiac and cardiac lesions were treated with SBRT. For dose specification, in 15 of 16 patients, the prescription dosage was 36 Gy in three fractions (70% isodose). In one patient, the target lesion was inside the heart, and the prescription dosage was 30 Gy in three fractions (70% isodose). RESULTS: Regarding response to stereotactic radiotherapy, we recorded one (6%) complete response (CR), six (37%) partial responses (PR), five (32%) stable disease (SD) and four (25%) local failures. Median interval to local failure was 5.2 (range, 3-12) months. The cause of death was distant progression of disease in all four patients. Compliance to treatment was excellent; no patient developed cardiological symptoms or electrocardiographic abnormalities, even months after SBRT. CONCLUSIONS: Results of our retrospective study indicate that SBRT represents a safe and effective treatment option for patients with cardiac and paracardiac metastases.

Breast cancer following Hodgkin's Disease: the experience of the University of Florence.

The advent of effective chemo-radiotherapy has made Hodgkin Disease (HD) a highly curable malignancy, but the great improvement in survival rates allowed the observation in long-term survivors of several treatment complications. Secondary malignancies are the most serious complications and breast cancer (BC) represents the most common solid tumor among female survivors. The aim of our analysis is to describe the clinico-pathological characteristics and management of BC occurred after HD treatment. Between 1960 and 2003, 2,039 patients were treated for HD at the Department of Radiotherapy-Oncology of the Florence University. In this study we considered 1,538 patients on whom a minimum follow up of 6 months had been obtained. Of these, 725 were women. The most represented histological subtype was nodular sclerosis (50.6%). Supradiaphragmatic alone or with subdiaphragmatic complementary extended field radiotherapy was delivered to 83.1% of patients while supradiaphragmatic involved field radiotherapy was delivered to 10.7% of patients. Concerning the characteristics and incidence of BC, we focused our analysis exclusively on the female group. We found that BC occurred in 39, with an overall incidence of 5.4%. The mean interval after Hodgkin treatment was 19.5 years (SD +/- 9.0). The median age of BC diagnosis was 50.8 years (SD +/- 13.3) while the median age of Hodgkin diagnosis was 31.2 years (SD +/- 14.5). Thirty-seven women received mediastinal irradiation. We observed a decreasing trend of the secondary BC incidence with increasing age of Hodgkin treatment with the maximum incidence registered in women treated at age 20 or younger. In Our Institute we perform a whole life follow up and recommend that annual mammography begins 10 years after HD treatment or, in any case, not later than age 40.

Analysis of skin dose distribution for the prediction of severe radiation dermatitis in head and neck squamous cell carcinoma patients treated with concurrent chemo-radiotherapy.

BACKGROUND: We investigated whether the pattern of intensity-modulated radiotherapy (IMRT) dose distribution to the skin can be correlated with the development of G3/G4 radiation dermatitis (RD). METHODS: A frequency-matched cohort analysis was perfomed on patients treated with IMRT and concurrent cisplatin or cetuximab. Risk ratios were obtained by fitting Poisson regression models. RESULTS: The incidence of G3/G4 RD was 41.1% in 90 patients included (50% vs 36.6% in the cetuximab and cisplatin cohorts, respectively). In multivariate analysis, PS ≥ 1 and weight loss at RT completion >10 kg were the only factors that retained significance. The best dosimetric predictive accuracy was provided by 19.9 cc and 5.8 cc of skin ring 2 mm V50 and V60, respectively (AUC: 0.61 for both). CONCLUSION: Along with clinical factors, the pattern of dose distribution to a ring structure localized 2 mm below the patient's surface may help predict the development of severe RD.

Non-pegylated liposomal doxorubicin in combination with cyclophosphamide or docetaxel as first-line therapy in metastatic breast cancer: a retrospective analysis.

AIMS AND BACKGROUND: Anthracyclines such as doxorubicin play a central role in the management of advanced breast cancer. Unfortunately, the clinical benefits of anthracyclines are limited by cardiotoxicity that can lead to the development of potentially fatal congestive heart failure. In order to limit anthracycline-related cardiotoxicity, liposomal formulations of doxorubicin have been developed. This retrospective analysis evaluated the experience obtained with non-pegylated liposomal doxorubicin as first-line therapy in 34 patients with metastatic breast cancer. METHODS: Patients received non-pegylated liposomal doxorubicin in combination with either cyclophosphamide (n = 14) or docetaxel (n = 20) for up to eight cycles, and efficacy and safety were assessed according to standard criteria. RESULTS: The overall response rate was 71%. The median progression-free survival was 8 months in patients receiving non-pegylated liposomal doxorubicin plus cyclophosphamide and 13.8 months in those receiving non-pegylated liposomal doxorubicin plus docetaxel (P = 0.2). The most commonly observed toxicities were grade 1-2 leucopenia, alopecia, nausea and vomiting; no grade 3-4 toxicities were observed. Overall, three patients (9%) experienced grade 1 cardiac toxicity. CONCLUSIONS: Our results support the use of non-pegylated liposomal doxorubicin as an alternative to conventional doxorubicin formulations in combination regimens for the first-line therapy of metastatic breast cancer.

Concurrent cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy and radiotherapy for early breast carcinoma.

PURPOSE: The optimal sequencing of adjuvant chemotherapy (CT) and radiation therapy (RT) in patients with early-stage breast cancer remains unclear. PATIENTS AND METHODS: We retrospectively compared 485 patients treated with conservative breast surgery and postoperative whole-breast RT and six courses of CMF (cyclophosphamide 600 mg/m(2), methotrexate 40 mg/m(2), and 5-fluorouracil 600 mg/m(2)) with 300 patients who received postoperative CMF only and with 509 patients treated with postoperative whole-breast RT only. The mean radiation dose delivered was 50 Gy (range, 46-52 Gy) with standard fractionation. The boost dose was 6-16 Gy according to resection margins and at the discretion of the radiation oncologist. Acute and late RT toxicity were scored using respectively the Radiation Therapy Oncology Group and the Late Effects in Normal Tissues Subjective, Objective, Management and Analytic scale. RESULTS: A slightly higher Grade 2 acute skin toxicity was recorded in the concurrent group (21.2% vs. 11.2% of the RT only group, p < 0.0001). RT was interrupted more frequently in the CMF/RT group respective to the RT group (8.5% vs. 4.1%; p = 0.006). There was no difference in late toxicity between the two groups. All patients in the concurrent group successfully received the planned dose of RT and CT. Local recurrence rate was 7.6% in CT/RT group and 9.8% in RT group; this difference was not statistically significant at univariate analysis (log-rank test p = 0.98). However, at multivariate analysis adjusted also for pathological tumor, pathological nodes, and age, the CT/RT group showed a statistically lower rate of local recurrence (p = 0.04). CONCLUSIONS: Whole-breast RT and concurrent CMF are a safe adjuvant treatment in terms of toxicity.

Advantage of deep inspiration breath hold in left-sided breast cancer patients treated with 3D conformal radiotherapy.

PURPOSE: To compare 3D-conformal radiotherapy (3D-CRT) treatment plans based on free-breathing (FB) and deep inspiration breath hold (DIBH) and investigated whether DIBH technique enables a decrease of cardiac left anterior descending coronary artery (LADCA) and lungs dose with respect to the FB. METHODS: Twenty-three left-sided breast cancer patients referred for breast radiotherapy were included. The planning target volume (PTV) encompassed the breast and organs at risk including heart, LADCA, lungs, and contralateral breast, which were contoured in FB and DIBH CT scans. Dose to PTV was 50 Gy in 25 fractions. Two treatment plans were generated for each patient: FB-3D-CRT and DIBH-3D-CRT. Dosimetry parameters were obtained from dose volume histograms. Data were compared using the paired-sample Wilcoxon signed rank test. RESULTS: For heart, LADCA, and left lung, a significant dose reduction was found using DIBH technique. By using DIBH, an average reduction of 25% was observed in LADCA for the volume receiving 20 Gy and of 48% considering the mean heart dose. CONCLUSIONS: The DIBH technique results in a significant decrease of dose to the heart, LADCA, and left lung compared to FB.

Limited-stage small-cell lung cancer treated with early chemo-radiotherapy: the impact of effective chemotherapy.

AIMS AND BACKGROUND: Small cell lung cancer is characterized by an aggressive clinical course and a high sensitivity to both chemotherapy and radiotherapy. We present the Florence University experience in concurrent early radio-chemotherapy in patients affected by limited-stage small cell lung cancer, with particular emphasis on treatment safety, disease outcome and prognostic factors. METHODS AND STUDY DESIGN: Fifty-seven patients were treated between June 2000 and February 2005. All patients underwent platinum-based chemotherapy, administered intravenously following two different regimens, for at least three cycles. Eighteen patients (31.6%) received epirubicin and ifosfamide in 3-week cycles alternating with etoposide and cisplatin, administered on day 1 to 3; 39 patients (68.4%) received etoposide and cisplatin. A total of 6 cycles were planned. Radiotherapy was administered concurrently to the first cycle of etoposide and cisplatin. RESULTS: Clinical stage (P = 0.036) and number of chemotherapy courses (P = 0.009) emerged as the only significant death predictors at univariate analysis. Number of chemotherapy courses persisted as a significant death predictor also at multivariate regression analysis, with a reduced death risk for 5-6 chemotherapy cycles in comparison to 3-4 cycles (hazard ratio, 0.44). At a mean follow up of 38.5 months (standard deviation, 3.24 years; range, 6-164 months), considering the best overall tumor response achieved at any time during the whole treatment period, we obtained 32 complete responses (56.1%), 23 partial responses (40.3%) and 2 stable diseases. CONCLUSIONS: Our analysis showed that concurrent early radio-chemotherapy in limited-stage small cell lung cancer treatment represents a safe and effective approach in patients. We confirmed the relevant impact on overall survival of effective chemotherapy delivery.

Post-operative radiotherapy in N2 non-small cell lung cancer: a retrospective analysis of 175 patients.

BACKGROUND AND PURPOSE: Post-operative radiotherapy (PORT) in radically resected non-small cell lung cancer (NSCLC) has the aim to reduce loco regional recurrence and to improve overall survival. PORT has been evaluated in several trials but indication to post-operative treatment in N2 patients is still debated. MATERIAL AND METHODS: We retrospectively analyzed 175 patients treated at University of Florence between 1988 and 2004 with completely resected NSCLC stages IIIA-IIIB, N2 disease. Surgery consisted in a lobectomy in 58.9% and in a bi-lobectomy or in a pneumonectomy in 41.1% of patients. One hundred and nineteen patients underwent PORT and 56 patients did not receive PORT (no-PORT). RESULTS: At a median follow-up of 27.6 months (range 4-233 months), we found a significant reduction in local recurrence (LR) in PORT group (log-rank test p=0.015; HR: 0.45; 95%CI: 0.24-0.87). No statistical difference were found in terms of overall survival (OS) (log-rank test p=0.92). Concerning other prognostic factors, male sex emerged as statistically significant (HR:4.33;1.04-18.02) on local progression free survival (LPFS) at univariate analysis. Acute and long-term toxicity was mild. CONCLUSION: Our retrospective analysis showed that PORT may improve local disease control in N2 NSCLC patients with an acceptable treatment-related toxicity.

Radiotherapy timing in 4,820 patients with breast cancer: university of florence experience.

PURPOSE: To analyze the relationship between a delay in radiotherapy (RT) after breast-conserving surgery and ipsilateral breast recurrence (BR). METHODS AND MATERIALS: We included in our analysis 4,820 breast cancer patients who had undergone postoperative RT at the University of Florence. The patients were categorized into four groups according to the interval between surgery and RT (T1, <60 days; T2, 61-120 days; T3, 121-180 days; and T4, >180 days). RESULTS: On multivariate analysis, the timing of RT did not reach statistical significance in patients who received only postoperative RT (n = 1,935) or RT and hormonal therapy (HT) (n = 1,684) or RT, chemotherapy (CHT), and HT (n = 529). In the postoperative RT-only group, age at presentation, surgical margin status, and a boost to the tumor bed were independent prognostic factors for BR. In the RT plus HT group, age at presentation and boost emerged as independent prognostic factors for BR (p = 0.006 and p = 0.049, respectively). Finally, in the RT, CHT, and HT group, only multifocality was an independent BR predictor (p = 0.01). Only in the group of patients treated with RT and CHT (n = 672) did multivariate analysis with stepwise selection show RT timing as an independent prognostic factor (hazard ratio, 1.59; 95% confidence interval, 1.01-2.52; p = 0.045). Analyzing this group of patients, we found that most patients included had worse prognostic factors and had received CHT consisting of cyclophosphamide, methotrexate, and 5-fluorouracil before undergoing RT. CONCLUSION: The results of our study have shown that the timing of RT itself does not affect local recurrence, which is mainly related to prognostic factors. Thus, the "waiting list" should be thought of as a "programming list," with patients scheduled for RT according to their prognostic factors.