Alessio Bruni

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.

Management of Stage II testicular seminoma over a period of 40 years

OBJECTIVES To review the treatment, toxicity, and outcomes in patients with Stage II seminoma after orchidectomy. MATERIALS AND METHODS A retrospective chart review of all patients with Stage II seminoma referred for initial treatment, from 1965 to 2005, was performed. Treatment approaches, toxicity, and outcomes were analyzed. RESULTS A total of 106 patients (83 with Stage IIA, 19 with Stage IIB, and 4 with Stage IIC) were seen between 1965 and 2005. Median age at diagnosis was 36 years (range: 19-71). Median follow-up was 21 years (range: 1.2-42). Eighty-nine patients were treated with adjuvant radiotherapy alone; 13 patients received a combined treatment modality with chemotherapy and radiotherapy after orchidectomy, 4 patients were treated with chemotherapy alone. Generally the treatment was well tolerated, with the main toxicity occurring in patients treated with extended-field radiotherapy. The 5-year disease-specific survival was 96% for the entire group. The 5-year relapse-free survivals for Stages IIA, IIB, and IIC disease were 94%, 72.5%, and 75%, respectively. Fifteen patients developed a relapse and were managed by chemotherapy; 5 of them achieved complete remission and remain free from further recurrence at last follow-up, while 10 died of the disease. Second malignancies were diagnosed in 4 (3.7%) patients during the follow-up. CONCLUSIONS In Stage IIA seminoma, radiotherapy continues to provide excellent results, as the majority of patients will be cured with this treatment alone. Radiotherapy or chemotherapy should be offered as an alternative to Stage IIB patients. Chemotherapy remains the treatment of choice for Stage IIC seminoma.

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.

Efficacy of stereotactic body radiotherapy in oligorecurrent and in oligoprogressive prostate cancer: new evidence from a multicentric study

Background:The aim of the present study is to evaluate the impact of metastases-directed stereotactic body radiotherapy in two groups of oligometastatic prostate cancer (PC) patients: oligorecurrent PC and oligoprogressive castration-resistant PC (oligo-CRPC).Methods:Inclusion criteria of the present multicentre retrospective analysis were: (1) oligorecurrent PC, defined as the presence of 1–3 lesions (bone or nodes) detected with choline positron emission tomography or CT plus bone scan following biochemical recurrence; (2) oligo-CRPC, defined as metastases (bone or nodes) detected after a prostatic-specific antigen rise during androgen deprivation therapy (ADT). Primary end points were: distant progression-free survival (DPFS) and ADT-free survival in oligorecurrent PC patients; DPFS and second-line systemic treatment-free survival in oligo-CRPC patients.Results:About 100 patients with oligorecurrent PC (139 lesions) and 41 with oligo-CRPC (70 lesions), treated between March 2010 and April 2016, were analysed. After a median follow-up of 20.4 months, in the oligorecurrent group 1- and 2-year DPFS were 64.4 and 43%. The rate of LC was 92.8% at 2 years. At a median follow-up of 23.4 months, in the oligo-CRPC group 1- and 2-year DPFS were 43.2 and 21.6%. Limitations include the retrospective design.Conclusions:Stereotactic body radiotherapy seems to be a useful treatment both for oligorecurrent and oligo-CRPC.

Reirradiation in head and neck recurrent or second primary tumor: efficacy, safety, and prognostic factors

Aims and background We investigated efficacy, safety, and prognostic factors of reirradiation in patients with recurrent or second primary head and neck cancer. Methods Records of 75 consecutive patients treated with reirradiation between August 2005 and December 2013 were reviewed. Results Median overall survival (OS) and cancer-specific survival (CSS) were 29.5 and 33.6 months. Median local control (LC) and progression-free survival (PFS) were 21.7 and 16.2 months. Univariate analysis showed that patients younger than 70 years, with a Karnofsky Performance Status (KPS) >90 or with 2 or less comorbidities at time of reirradiation, have a better OS; KPS >90 and biological equivalent dose (BED) >72 Gy positively influenced the PFS. At multivariate analysis, KPS at reirradiation was an independent predictive factor for OS, while BED was an independent predictive factor for CSS and OS. At univariate analysis, patients with planning target volume (PTV) >221 mL had worse LC and PFS rates, with results confirmed at multivariate analysis. The rate of fatal treatment-related adverse events was 6.7% (3 carotid blowout, 1 soft tissue necrosis, and 1 thromboembolic event). Conclusions This study confirms the role and outcomes of reirradiation. A careful selection of patients could minimize acute and late side effects and influence survival: elderly patients, with significant medical comorbidities or poor KPS, are worse candidate for reirradiation. Total dose delivered with reirradiation and PTV appear to be other potential prognostic factors. Further studies of dose escalation are needed to establish the total dose that could achieve better LC rates with a safer toxicity profile.

The role of stereotactic ablative radiotherapy in oncological and non-oncological clinical settings: highlights from the 7th Meeting of AIRO--Young Members Working Group (AIRO Giovani).

Stereotactic ablative radiotherapy is a modern cancer treatment strategy able to deliver highly focused radiation in one or a few fractions with a radical intent in several clinical settings. Young radiation oncologists need a constant and tailored update in this context to improve patient care in daily clinical practice. A recent meeting of AIRO Giovani (AIRO - Young Members Working Group) was specifically addressed to this topic, presenting state-of-the-art knowledge, based on the latest evidence in this field. Highlights of the congress are summarized and presented in this report, including thorough contributions of the speakers dealing with the role of stereotactic ablative radiotherapy in both oncological and non-oncological diseases, divided according to anatomical and clinical scenarios: intra-cranial settings (brain malignant primary tumors, metastases, benign tumors and functional disorders) and extra-cranial indications (lung primary tumors and metastases, thoracic re-irradiation, liver, lymph node and bone metastases, prostate cancer). With literature data discussed during the congress as a background, stereotactic ablative radiotherapy has proved to be a consolidated treatment approach in specific oncological and non-oncological scenarios, as well as a promising option in other clinical settings, requiring a further prospective validation in the near future. We herein present an updated overview of stereotactic ablative radiotherapy use in the clinic.

Oral Ibandronate in Metastatic Bone Breast Cancer: The Florence University Experience and a Review of the Literature

Abstract Ibandronate is an amino-bisphosphonate approved in metastatic breast cancer to reduce skeletal complications and to alleviate bone pain. We report our experience about the safety of oral ibandronate and review the literature. We treated 44 patients and administered 524 cycles of oral ibandronate (a single cycle was defined as a 50 mg capsule once daily for 28 days) with a median of 12 cycles (range 6-24). At a median follow-up of 18.5 months (range 6-28) the mean pain score decreased from 1.59 (SD±0.97) at baseline to 0.41 (SD±0.72) after 48 weeks of treatment. The mean analgesic score was 1.89 (SD±1.37) at baseline and 1.46 (SD±1.62) after 48 weeks of treatment. Ibandronate was generally well-tolerated; we had no Grade 3-4 adverse events. No patients had deterioration of renal function. No patients developed bisphosphonate-associated osteonecrosis of the jaw. Our experience confirmed that ibandronate may be a useful and safe co-analgesic to conventional treatments for bone pain in selected metastatic breast cancer patients.

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.

Stereotactic Ablative Radiotherapy as an Alternative to Lobectomy in Patients With Medically Operable Stage I NSCLC: A Retrospective, Multicenter Analysis

Background: Stereotactic ablative body radiation therapy (SBRT) has evolved as the standard treatment for patients with inoperable stage I non–small‐cell lung cancer (NSCLC). We report the results of a retrospective analysis conducted on a large, well‐controlled cohort of patients with stage I to II NSCLC who underwent lobectomy (LOB) or SBRT. Materials and Methods: One hundred eighty‐seven patients with clinical‐stage T1a‐T2bNoMO NSCLC were treated in 2 academic hospitals between August 2008 and May 2015. Patients underwent LOB or SBRT; those undergoing SBRT were sub‐classified as surgical candidates and nonsurgical candidates, according to the presence of surgical contraindications or comorbidities. Results: In univariate analysis, no significant difference was found in local control between patients who underwent SBRT and LOB, with a trend in favor of surgery (hazard ratio [HR], 0.27; 95% confidence interval [CI], 0.07‐1.01; P < .053). Univariate analysis showed that overall survival (OS) was significantly better in patients who underwent LOB (HR, 0.44; 95% CI, 0.23‐0.85) with a 3‐year OS of 73.4% versus 65.2% for surgery and radiation therapy patients, respectively (P < .01). However, no difference in OS was observed between operable patients undergoing SBRT and patients who underwent LOB (HR, 1.68; 95% CI, 0.72‐3.90). Progression‐free survival was comparable between patients who underwent LOB and SBRT (HR, 0.61; P = .09). Conclusion: SBRT is a valid therapeutic approach in early‐stage NSCLC. Furthermore, SBRT seems to be very well‐tolerated and might lead to the same optimal locoregional control provided by surgery for patients with either operable or inoperable early‐stage NSCLC.