Paolo Bastiani

Accelerated partial breast irradiation using intensity-modulated radiotherapy versus whole breast irradiation: 5-year survival analysis of a phase 3 randomised controlled trial

BACKGROUND Accelerated partial breast irradiation (APBI) has been introduced as an alternative treatment method for selected patients with early stage breast cancer (BC). Intensity-modulated radiotherapy (IMRT) has the theoretical advantage of a further increase in dose conformity compared with three-dimensional techniques, with more normal tissue sparing. The aim of this randomised trial is to compare the local recurrence and survival of APBI using the IMRT technique after breast-conserving surgery to conventional whole-breast irradiation (WBI) in early stage BC. METHODS This study was performed at the University of Florence (Florence, Italy). Women aged more than 40years affected by early BC, with a maximum pathological tumour size of 25mm, were randomly assigned in a 1:1 ratio to receive either WBI or APBI using IMRT. Patients in the APBI arm received a total dose of 30 Gy to the tumour bed in five daily fractions. The WBI arm received 50Gy in 25 fractions, followed by a boost on the tumour bed of 10Gy in five fractions. The primary end-point was occurrence of ipsilateral breast tumour recurrences (IBTRs); the main analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT02104895. FINDINGS A total of 520 patients were randomised (260 to external WBI and 260 to APBI with IMRT) between March 2005 and June 2013. At a median follow-up of 5.0 years (Interquartile Range (IQR) 3.4-7.0), the IBTR rate was 1.5% (three cases) in the APBI group (95% confidence interval (CI) 0.1-3.0) and in the WBI group (three cases; 95% CI 0.0-2.8). No significant difference emerged between the two groups (log rank test p=0.86). We identified seven deaths in the WBI group and only one in the APBI group (p=0.057). The 5-year overall survival was 96.6% for the WBI group and 99.4% for the APBI group. The APBI group presented significantly better results considering acute (p=0.0001), late (p=0.004), and cosmetic outcome (p=0.045). INTERPRETATION To our knowledge, this is the first randomised study using the IMRT technique for APBI delivery. No significant difference in terms of IBTR and overall survival was observed between the two arms. APBI displayed a significantly better toxicity profile.

Adjuvant radiotherapy after extrapleural pneumonectomy for mesothelioma. Prospective analysis of a multi-institutional series

BACKGROUND AND PURPOSE To evaluate survival, locoregional control and toxicity in a series of 56 mesothelioma patients treated from May 2005 to May 2010 with post-operative radiotherapy after extrapleural pneumonectomy (EPP) in three Italian Institutions (Brescia, Florence, and Modena). MATERIAL AND METHODS Fifty-six patients treated with adjuvant radiotherapy (RT) after EPP were analyzed. Four patients were treated with 3DCRT, 50 with IMRT and two with helical tomotherapy. Forty-five to 50 Gy in 25 fractions were given to the affected hemithorax and to ipsilateral mediastinum, with a simultaneous integrated boost to the sites of microscopically involved margins up to 60 Gy in 20/56 cases. RESULTS Three year locoregional control (LRC), distant metastasis free (DMF), disease free (DF), disease specific (DSS) and overall survival (OS) rates are 90%, 66%, 57%, 62%, and 60%, respectively. CONCLUSION Postoperative RT with modern techniques is an effective method to obtain excellent local control and cure rates in mesothelioma patients submitted to EPP.

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.

Loco regional failure pattern after lumpectomy and breast irradiation in 4185 patients with T1 and T2 breast cancer. Implications for nodal irradiation

The aim of this study is to determinate incidence and risk factors for loco regional failure (LRR) (breast, supraclavicular, axillary and internal mammary nodes) and indications for nodal irradiation. From January 1980 to December 2001, 4185 patients with T1–T2 breast cancer were treated with conservative surgery and whole breast radiotherapy without nodal irradiation at the University of Florence. The median age was 55 years (range 19–86). All patients were followed for a median of eight years (range 3 months to 20 years). Multivariate analysis showed as independent prognostic factors for isolated nodal relapse (NR) the presence of more than three positive lymph nodes (PAN) (p = 0.001), angiolymphatic invasion (p = 0.002) and pT2 (p = 0.02). However, only 4.8% of patients with more than three PAN developed NR as the only site of recurrence. Having one to three PAN was not associated with an increased risk of NR. We believe that it is not necessary to prescribe nodal irradiation to patients with negative or one to three PAN. Regarding patients with more than three PAN, the number of isolated NR is also small to routinely justify a node irradiation.

ACCELERATED INTENSITY-MODULATED EXTERNAL RADIOTHERAPY AS A NEW TECHNICAL APPROACH TO TREAT THE INDEX QUADRANT AFTER CONSERVING SURGERY IN EARLY BREAST CANCER: A PRELIMINARY STUDY

Purpose We present a novel technical approach to treat the index quadrant after conserving surgery in patients with early breast cancer and study its clinical feasibility. Methods and material Patients selected for the study, after breast conserving surgery with histologically verified breast carcinoma, signed a full informed consent to intensity-modulated external radiotherapy of the partial breast. Treatment was performed with the 6 MV beam from one of the Elekta Precise LINAC units installed in our Department. The prescribed dose was 30 Gy in 5 fractions in 10 days. Results Acute toxicity was minimal. No skin changes were noted during treatment or during the first 6 months after radiotherapy treatment. Conclusions Accelerated partial breast irradiation using intensity-modulated external radiotherapy is technically feasible. We think the approach will give good results in terms of local control, toxicity and quality of life, at the same time sparing resources for the patient and health care system.

Waldeyer's ring (WR) involvement in Hodgkin's disease

Of 750 patients with stage I, II or III Hodgkins disease, admitted to the University and Hospital Radiotherapy Divisions, Florence, between 1960 and 1981, 28 (3.7%) had involvement of Waldeyers ring (WR). In 25 patients there was associated involvement of upper cervical nodes. Other factors associated with WR involvement were age over 55 years, lymphocyte predominant histological sub-type, uninvolved mediastinum, and size of involved upper cervical nodes greater than that of involved lower cervical nodes. These factors help to define indications for prophylactic irradiation of WR.

Localized prostate cancer treated with intensity-modulated radiotherapy.

Aims and background The development and use of new radiotherapy techniques, especially 3D conformal radiotherapy or intensity-modulated radiotherapy, has allowed the safe application of high doses of external beam radiotherapy without increasing toxicity. The aim of this analysis was to describe the acute and when possible late toxicity and the feasibility on using intensity-modulated radiotherapy into our routine work. Patients and methods From June 2003 to December 2004, 60 patients with prostate cancer underwent high dose (80 Gy) radiotherapy treatment with intensity-modulated radiotherapy at the University of Florence. In the current analysis, we included patients without clinical or radiographic evidence of distant disease at the time of the first evaluation in the radiotherapy unit. Results Intensity-modulated radiotherapy treatments were delivered successfully without any interruption or technical problem. High-dose intensity-modulated radiotherapy was well tolerated acutely. Four patients (10%) developed grade 1 late rectal toxicity after completion of intensity-modulated radiotherapy and 8 patients (20%) developed grade 1 late urinary symptoms. Conclusions Intensity-modulated radiotherapy is the approach of choice for high-dose radiotherapy delivery. No patient had severe toxicity (grade 3) despite the high dose delivered. From a cost-benefit point of view, our experience shows that delivery of intensity-modulated radiotherapy requires only minor corrections to the ordinary activity schedule.

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.

Vinorelbine-based chemo-radiotherapy in non-small cell lung cancer.

AIMS AND BACKGROUND Concomitant radio-chemotherapy improves survival of patients with locally advanced non-small cell lung cancer, with a better local-regional control. METHODS AND STUDY DESIGN We report our experience with vinorelbine-based chemotherapy in neoadjuvant and radical settings in 43 patients. Regimens consisted of cisplatin plus vinorelbine in 74.4% patients and carboplatin plus vinorelbine in 14.0%; 11.6% underwent mono-chemotherapy with oral vinorelbine. We estimated the crude probability of death or local recurrence by the Kaplan-Meier method. Cox regression models were used to identify the main significant predictors of death or local recurrence. RESULTS A significant effect of the response to treatment was shown on both local disease free-survival (P = 0.004) and overall survival (P <0.0001). Patients with progressive disease after primary treatment had a significantly higher risk of further relapse at both univariate (P = 0.046) and multivariate regression analysis (P = 0.014) than patients with a complete response. They also showed a significantly higher risk of death at both univariate (P = 0.0005) and multivariate regression analysis (P <0.0001) than patients with a complete response. The most common toxicity was hematologic and gastroenteric. We recorded grade III/IV leukopenia in 11%, anemia in 6%, and esophagitis in 14% of the patients. CONCLUSIONS Our experience showed that vinorelbine-based chemotherapy is an effective and safe regimen, in association with a platinum compound and thoracic radiotherapy.

Radiotherapy timing in the treatment of limited-stage small cell lung cancer: the impact of thoracic and brain irradiation on survival

Aims and Background Small cell lung cancer is an aggressive histologic subtype of lung cancer in which the role of chemotherapy and radiotherapy has been well established in limited-stage disease. We retrospectively reviewed a series of limited-stage small cell lung cancers treated with chemotherapy and thoracic and brain radiotherapy. Methods and Study Design A total of 124 patients affected by limited-stage small cell lung cancer has been treated over 10 years in our Institute. Fifty-three patients (42.8%) had concomitant radio-chemotherapy treatment and 71 patients (57.2%) a sequential treatment. Eighty-eight patients (70.9%) underwent an association of a platinum-derived drug (cisplatinum or carboplatinum) and etoposide. Prophylactic cranial irradiation was planned in all patients with histologically proven complete response to primary radio-chemotherapy. Results With a mean follow-up of 2.2 years, complete response was obtained in 50.8% of cases. We found a significant difference between different radio-chemotherapy association approaches (P = 0.007): percentages of overall survival were respectively 10.0%, 12.9% and 5.6% in early, late concomitant and sequential radiochemotherapy timing. Cranial prophylaxis did not seem to influence overall survival (P = 0.21) or disease-free survival for local relapse (P = 0.34). Conclusions Concomitant radio-chemotherapy is the best approach according to our experience. Our results show a benefit of prophylactic cranial irradiation in distant metastasis-free survival.