Andrea Rampini

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.

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.

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

Abstract:  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.

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.

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

PurposeThis 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 methodsBetween 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).ResultsRegarding 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.ConclusionsResults of our retrospective study indicate that SBRT represents a safe and effective treatment option for patients with cardiac and paracardiac metastases.RiassuntoObiettivoScopo di questo lavoro è valutare la tossicità acuta e il controllo locale nel trattamento di pazienti sottoposti a radioterapia stereotassica extracranica (SBRT) per lesioni metastatiche paracardiache e cardiache, definite come tali se localizzate entro 1 cm dal cuore o nel contesto del suo parenchimaMateriali e metodiFra gennaio 2009 e maggio 2011, 16 pazienti con lesioni paracardiache e cardiache sono stati sottoposti a SBRT. In 15/16 pazienti la dose prescritta è stata di 36 Gy in 3 frazioni (all’isodose del 70%). In un paziente la lesione target era intracardiaca, e la dose di prescrizione è stata di 30 Gy in 3 frazioni (all’isodose del 70%).RisultatiPer quanto concerne la risposta alla radioterapia stereotassica, è stata registrata 1 (6%) risposta completa (CR), 6 (37%) risposte parziali (PR), 5 (32%) stabilità di malattia (SD) e 4 (25%) progressioni locali. L’intervallo mediano alla progressione locale è stato di 5,2 mesi (range 3–12 mesi). La tolleranza al trattamento è stata ottimale; nella serie di pazienti trattati nessuno ha sviluppato segni o sintomi di natura cardiologica in conseguenza della SBRT.ConclusioniI risultati della nostra analisi retrospettiva indicano che la SBRT rappresenta una opzione terapeutica sicura ed efficace per metastasi cardiache e paracardiache.

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.

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

AimTo 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.MethodsThe 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.ResultsThe 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.ConclusionA 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.

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.

Radioterapia stereotassica extracranica per metastasi cardiache e paracardiache: esperienza dell'Università di Firenze

PurposeThis 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 methodsBetween 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).ResultsRegarding 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.ConclusionsResults of our retrospective study indicate that SBRT represents a safe and effective treatment option for patients with cardiac and paracardiac metastases.RiassuntoObiettivoScopo di questo lavoro è valutare la tossicità acuta e il controllo locale nel trattamento di pazienti sottoposti a radioterapia stereotassica extracranica (SBRT) per lesioni metastatiche paracardiache e cardiache, definite come tali se localizzate entro 1 cm dal cuore o nel contesto del suo parenchimaMateriali e metodiFra gennaio 2009 e maggio 2011, 16 pazienti con lesioni paracardiache e cardiache sono stati sottoposti a SBRT. In 15/16 pazienti la dose prescritta è stata di 36 Gy in 3 frazioni (all’isodose del 70%). In un paziente la lesione target era intracardiaca, e la dose di prescrizione è stata di 30 Gy in 3 frazioni (all’isodose del 70%).RisultatiPer quanto concerne la risposta alla radioterapia stereotassica, è stata registrata 1 (6%) risposta completa (CR), 6 (37%) risposte parziali (PR), 5 (32%) stabilità di malattia (SD) e 4 (25%) progressioni locali. L’intervallo mediano alla progressione locale è stato di 5,2 mesi (range 3–12 mesi). La tolleranza al trattamento è stata ottimale; nella serie di pazienti trattati nessuno ha sviluppato segni o sintomi di natura cardiologica in conseguenza della SBRT.ConclusioniI risultati della nostra analisi retrospettiva indicano che la SBRT rappresenta una opzione terapeutica sicura ed efficace per metastasi cardiache e paracardiache.

Stereotactic body radiotherapy for cardiac and paracardiac metastases: University of Florence experience@@@Radioterapia stereotassica extracranica per metastasi cardiache e paracardiache: esperienza dell’Università di Firenze

PurposeThis 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 methodsBetween 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).ResultsRegarding 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.ConclusionsResults of our retrospective study indicate that SBRT represents a safe and effective treatment option for patients with cardiac and paracardiac metastases.RiassuntoObiettivoScopo di questo lavoro è valutare la tossicità acuta e il controllo locale nel trattamento di pazienti sottoposti a radioterapia stereotassica extracranica (SBRT) per lesioni metastatiche paracardiache e cardiache, definite come tali se localizzate entro 1 cm dal cuore o nel contesto del suo parenchimaMateriali e metodiFra gennaio 2009 e maggio 2011, 16 pazienti con lesioni paracardiache e cardiache sono stati sottoposti a SBRT. In 15/16 pazienti la dose prescritta è stata di 36 Gy in 3 frazioni (all’isodose del 70%). In un paziente la lesione target era intracardiaca, e la dose di prescrizione è stata di 30 Gy in 3 frazioni (all’isodose del 70%).RisultatiPer quanto concerne la risposta alla radioterapia stereotassica, è stata registrata 1 (6%) risposta completa (CR), 6 (37%) risposte parziali (PR), 5 (32%) stabilità di malattia (SD) e 4 (25%) progressioni locali. L’intervallo mediano alla progressione locale è stato di 5,2 mesi (range 3–12 mesi). La tolleranza al trattamento è stata ottimale; nella serie di pazienti trattati nessuno ha sviluppato segni o sintomi di natura cardiologica in conseguenza della SBRT.ConclusioniI risultati della nostra analisi retrospettiva indicano che la SBRT rappresenta una opzione terapeutica sicura ed efficace per metastasi cardiache e paracardiache.