Icro Meattini

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.

Stereotactic Radiotherapy for Adrenal Gland Metastases: University of Florence Experience

PURPOSE To evaluate a retrospective single-institution outcome after hypofractionated stereotactic body radiotherapy (SBRT) for adrenal metastases. METHODS AND MATERIALS Between February 2002 and December 2009, we treated 48 patients with SBRT for adrenal metastases. The median age of the patient population was 62.7 years (range, 43-77 years). In the majority of patients, the prescription dose was 36 Gy in 3 fractions (70% isodose, 17.14 Gy per fraction at the isocenter). Eight patients were treated with single-fraction stereotactic radiosurgery and forty patients with multi-fraction stereotactic radiotherapy. RESULTS Overall, the series of patients was followed up for a median of 16.2 months (range, 3-63 months). At the time of analysis, 20 patients were alive and 28 patients were dead. The 1- and 2-year actuarial overall survival rates were 39.7% and 14.5%, respectively. We recorded 48 distant failures and 2 local failures, with a median interval to local failure of 4.9 months. The actuarial 1-year disease control rate was 9%; the actuarial 1- and 2-year local control rate was 90%. CONCLUSION Our retrospective study indicated that SBRT for the treatment of adrenal metastases represents a safe and effective option with a control rate of 90% at 2 years.

Second-line chemotherapy with fotemustine in temozolomide-pretreated patients with relapsing glioblastoma: a single institution experience.

To evaluate efficacy and safety of fotemustine chemotherapy in temozolomide (TMZ) pretreated adults with recurrent glioblastoma multiforme (GBM). Primary endpoint was progression-free survival at 6 months. Twenty-seven patients (median age: 56 years; median Karnofsky performance status at progression: 80) with relapsed glioblastoma multiforme underwent fotemustine as second-line chemotherapy after failure of homogeneous postoperative treatment consisting of conformal radiotherapy (60 Gy in 30 fractions) with concomitant TMZ (75 mg/m2 per day), followed by six courses of TMZ (150–200 mg/m2 for 5 days every 28 days). Patients were assigned to Radiation Therapy Oncology Group recursive partitioning analysis classes for gliomas. After MRI-proven tumor relapse or progression, all patients underwent chemotherapy with fotemustine, given intravenously 100 mg/m2 every week for 3 consecutive weeks (induction phase) and then every 3 weeks (maintenance phase). Adequate liver, renal, and bone marrow functions were required. Toxicity grading was based on the National Cancer Institutes Common Toxicity Criteria (version 2.0). Response to treatment was assessed on MacDonald criteria. According to an intention-to-treat-analysis, data on all enrolled patients were included in statistical analysis. Eight partial responses (29.6%) and five cases of stable disease (18.5%) were observed. Median time to progression was 5.7 months. Progression-free survival at 6 months was 48.15%. Median survival from the beginning of fotemustine chemotherapy was 9.1 months. Median survival from diagnosis of glioblastoma was 21.2 months. Toxicity was manageable and mainly hematological (grade 3 thrombocytopenia: three cases; grade 4 leukopenia: one case). Fotemustine has shown therapeutic efficacy as single-drug second-line chemotherapy in treatment of TMZ pretreated patients.

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.

Prognostic value of positive human epidermal growth factor receptor 2 status and negative hormone status in patients with T1a/T1b, lymph node-negative breast cancer.

The objective of this study was to evaluate prognostic factors of local and distant recurrence in patients diagnosed with T1a and T1b, lymph node‐negative breast carcinoma (BC) with emphasis on human epidermal growth factor receptor 2 (HER2) status.

Organs at risk in the brain and their dose-constraints in adults and in children: A radiation oncologist’s guide for delineation in everyday practice

PURPOSE Accurate organs at risk definition is essential for radiation treatment of brain tumors. The aim of this study is to provide a stepwise and simplified contouring guide to delineate the OARs in the brain as it would be done in the everyday practice of planning radiotherapy for brain cancer treatment. METHODS Anatomical descriptions and neuroimaging atlases of the brain were studied. The dosimetric constraints used in literature were reviewed. RESULTS A Computed Tomography and Magnetic Resonance Imaging based detailed atlas was developed jointly by radiation oncologists, a neuroradiologist and a neurosurgeon. For each organ brief anatomical notion, main radiological reference points and useful considerations are provided. Recommended dose-constraints both for adult and pediatric patients were also provided. CONCLUSIONS This report provides guidelines for OARs delineation and their dose-constraints for the treatment planning of patients with brain tumors.

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.

OUTCOME AFTER CONSERVATIVE SURGERY AND BREAST IRRADIATION IN 5,717 PATIENTS WITH BREAST CANCER: IMPLICATIONS FOR SUPRACLAVICULAR NODAL IRRADIATION

PURPOSE To evaluate the outcome and predictive factors of patients who underwent breast-conserving surgery and adjuvant radiotherapy to the whole breast only, without supraclavicular nodal irradiation. METHODS AND MATERIALS A total of 5,717 patients with pT1-T4 breast cancer were treated at the University of Florence. The median age of the patient population was 55 years (range, 30-80 years). All patients were followed for a median of 6.8 years (range, 1-27 years). Adjuvant chemotherapy was recommended in 1,535 patients (26.9%). Tamoxifen was prescribed in 2,951 patients (51.6%). The patients were split into three groups according to number of positive axillary nodes (PAN): P1, negative axillary lymph nodes; P2, one to three PAN; P3, more than three PAN. RESULTS The P3 patients had a higher incidence of supraclavicular fossa recurrence (SFR) compared with P2 and P1 patients. However, the incidence of SFR in P3 patients was low (only 5.5%), whereas the incidence of distant metastases (DM) was 27.2%. Distant metastasis was the only independent prognostic factor for breast cancer survival. Additionally, in the subgroup of patients who developed local recurrence, DM was the most important death predictor. CONCLUSION Our series suggests that isolated SFR in patients who did not receive supraclavicular radiotherapy is infrequent, as well as in those patients who have more than three PAN, and SFR seems not to influence the outcome, which depends on DM occurrence.

Radiotherapy boost dose-escalation for invasive breast cancer after breast-conserving surgery: 2093 Patients treated with a prospective margin-directed policy

PURPOSE To investigate the outcome of invasive early breast cancer patients that underwent breast-conserving surgery and adjuvant radiotherapy (RT), treated with a prospective margin-directed institutional policy for RT boost dose, based on final margins status (FMS). METHODS AND MATERIALS A total of 2093 patients were treated between 2000 and 2008. 10 Gy boost was prescribed in case of FMS>5mm; 16 Gy boost with FMS between 2 and 5mm; 20 Gy boost in case of FMS<2mm or positive. RESULTS After a median follow up of 5.2 years, we recorded 41 local relapse (LR, 2%). Concerning LR free survival, age at diagnosis, nuclear grade, hormonal status, T-stage, adjuvant hormonal therapy and adjuvant chemotherapy emerged as significant parameters (p-values from log rank test <0.05). FMS, that directed the RT boost dose, did not have significant impact on LRFS (p=0.46). LR rates were 2.3% for FMS<2mm, 2.6% for 2-5mm FMS and 1.8% for FMS>5mm. At multivariate analysis, higher nuclear grade (p=0.045), triple negative subtype (p=0.036) and higher T-stage (p=0.02) resulted as the independent predictors of LR occurrence. CONCLUSIONS Our experience showed that a margin-directed policy of RT boost dose-escalation seems to reduce the negative impact of FMS on LR, but it is not able to overcome the unfavorable effect of higher nuclear grade, higher T stage and triple negative subtype.

Prognostic factors and clinical features in patients with leptominengeal metastases from breast cancer: a single center experience

Abstract Background: Meningeal carcinomatosis (MC) is a rare complication in breast cancer (BC) with no efficient modality of treatment yet found; overall survival (OS) generally did not exceed six months. We reviewed the experience of the University of Florence focusing on prognostic factors and MC survival. Patients and methods: We analyzed 33 patients treated for MC from BC between 2002 and 2010. Results: Mean OS from MC diagnosis was 4·9 months. At survival analysis clinical stage emerged as the only statistical significant parameter (P = 0·009) among BC diagnosis features. Among MC diagnosis parameters, more than three metastases at diagnosis (P = 0·037), multimodality treatment (P = 0·014) and poor performance status (P = 0·003) reached the statistical significance. At multivariate analysis only performance status at MC diagnosis maintained the statistical significance (P = 0·0047; HR: 3·34; CI 95% 1·45–7·73). Conclusions: Our experience confirms that performance status is probably the most important prognostic factor in these patients. Multimodality approach is probably the best option.