Benedetta Agresti

Accelerated Partial Breast Irradiation With IMRT: New Technical Approach and Interim Analysis of Acute Toxicity in a Phase III Randomized Clinical Trial

PURPOSE To evaluate with a randomized clinical trial the possibility of treating the index quadrant with external intensity-modulated radiotherapy (IMRT) in a selected group of patients with early-stage breast cancer and to analyze the acute toxicity. METHODS AND MATERIALS From September 2005, a randomized Phase III clinical trial has been conducted to compare conventional (tangential field) fractionated whole breast treatment (Arm A) with accelerated partial breast irradiation plus intensity-modulated radiotherapy (Arm B). For intensity-modulated radiotherapy, the clinical target volume was drawn with a uniform 1-cm margin around the surgical clips in three dimensions. The ipsilateral and contralateral breast, ipsilateral and contralateral lung, heart, and spinal cord were contoured as organs at risk. All the regions of interest were contoured according to the International Commission on Radiation Units and Measurements reports 50 and 62 recommendations. RESULTS In September 2008, 259 patients were randomized and treated. The mean clinical target volume in Arm B was 44 cm(3) and the mean planning target volume was 123 cm(3). The mean value of the ratio between the planning target volume and the ipsilateral breast volume was 21%. The rate of Grade 1 and Grade 2 acute skin toxicity was 22% and 19% in Arm A (Radiation Therapy Oncology Group scale), respectively. The tolerance in Arm B was excellent with only 5% Grade 1 and 0.8% Grade 2 acute skin toxicity. The planning constraints were fully satisfied in most patients. In a very few cases, this was not possible because of very unfavorable anatomy. Quality assurance procedures were performed according to our internal quality assurance protocol, with excellent results. CONCLUSION In the present preliminary analysis, we have demonstrated that accelerated partial breast irradiation is feasible, with very low acute toxicity.

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.

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.

Pediatric primary anaplastic ganglioglioma: a case report and review of the literature.

Gangliogliomas with anaplastic features are classified as grade III tumors by the World Health Organization. The clinical course and optimal treatment of anaplastic gangliogliomas have not been well understood to date. We report a case of a primary pure anaplastic ganglioglioma in a 14-year-old male treated with surgery and radiotherapy, who is disease-free 6 years after the diagnosis. A review of primary pure anaplastic gangliogliomas in children (between 3 and 21 years of age) is presented. Gross total removal and focal radiotherapy with a total dose of 54 Gy are recommended. The addition of chemotherapy should be evaluated. Prospective studies are needed to identify an appropriate chemotherapy schedule and to define biological factors in order to select those patients with a poor prognosis, who are to be treated with a more aggressive therapy.

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.

Role of chemotherapy in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a unique malignant head and neck cancer with clinical, demographic, and geographic features distinct from other head and neck epithelial malignancies. Non-keratinizing, poorly differentiated, and undifferentiated WHO types 2 and 3 is the most common subtypes of NPC. NPC is also characterized by its relatively high sensitivity to radiation, so that in the last decades radiotherapy (RT) has been the cornerstone of treatment. However, in the majority of cases NPC is discovered at locally advanced stage. The results are disappointing when RT alone is offered. The 5-year survival rates have been reported to be about 34–52%. The poor prognosis for advanced NPC led to increasing interests in exploring the use of chemotherapy (CT). NPC has been considered to be not only radiosensitive but also chemo-sensitive and has shown high response rate to various chemotherapeutic agents. Certainly, the treatment strategies for NPC will continue to change and evolve as a better understanding is gained of the molecular and immune mechanisms that drive this disease. We reviewed the current literature focusing on the role of CT and new-targeted agents.

Simultaneous integrated boost-intensity-modulated radiotherapy in head and neck cancer.

To review toxicity and outcomes in patients with head and neck cancer treated with simultaneous integrated boost–intensity‐modulated radiotherapy (SIB‐IMRT).

Salvage stereotactic re-irradiation with CyberKnife for locally recurrent head and neck cancer: a single center experience.

Aims and Background We report the toxicity and preliminary clinical outcome in patients affected by locally recurrent head and neck cancer treated with stereotactic reirradiation. Methods Between February 2012 and August 2013, 17 patients were treated with CyberKnife as stereotactic re-irradiation for locally recurrent head and neck cancer. All patients had previously received a full dose radiation treatment with radical intent, with a median total dose of 66 Gy (range, 50–70) delivered with standard fractionation. The median interval between the primary radiotherapy and re-irradiation was 24 months (range, 10–168). Results All patients completed the prescribed treatment, which was delivered in 5 fractions. The median tumor dose administered was 30 Gy (range, 25–35) prescribed to the 80% isodose line. Treatment sites were as follows: neck lymph nodes in 5 patients, paranasal sinuses in 5, oropharynx in 2, nasopharynx, and larynx, oral cavity, nasal fossa and parotid gland each in 1 patient. The median target volume treated was 58.7 cm3 (range, 8.5–211.3). Sixteen patients (94%) were evaluated for response. At a median follow-up of 7.5 months (range, 2–17), 4 patients achieved complete response (25%), 5 had partial response (31%) and 7 showed stable disease (44%). No patient showed in-field progression after re-irradiation. Grade 3 acute toxicity was noted in one patient only; no late side effect was observed during the follow-up. Conclusions Stereotactic re-irradiation with CyberKnife is an appealing non-surgical salvage treatment for selected patients with local-regionally recurrent head and neck cancer.

Treatment of invasive male breast cancer: a 40-year single-institution experience.

PurposeWe conducted a retrospective analysis to evaluate the management and outcome of invasive male breast cancer treated in a single-institution over a period of 40 years.Materials and methodsWe reviewed the clinical and pathological features of 60 male patients affected by breast carcinoma treated at our Radiotherapy Unit between 1971 and 2011. Tumours were classified according to histological type and the updated 2010 TNM classification of malignant tumours.ResultsAt a median follow-up of 8.9 [range, 0.6–20; standard deviation (SD), 4.98] years, 32 patients (53.3%) were alive and 16 patients died (26.7%) due to disease progression and 12 (20%) due to other causes. At univariate analysis for overall survival, pathological tumour size (p=0.031), histological subtype (p=0.013) and nodal status (p=0.006) emerged as significant predictors of death. At multivariate analysis, independent death predictors were advanced pathological tumour size (p=0.016), positive nodal status (p=0.003) and invasive cribriform histological type (p=0.0003).ConclusionsIn consideration of the rarity of the disease, many issues are still being debated, and future collaborative studies are required. However, our experience confirms the prognostic role of greater pathological tumour size and positive nodal status as unfavourable features for survival in male breast cancer.RiassuntoObiettivoAbbiamo condotto un’analisi retrospettiva per valutare il trattamento e la sopravvivenza di una serie di pazienti affetti da carcinoma mammario invasivo maschile trattati in un singolo centro in un periodo di 40 anni.Materiali e metodiAbbiamo analizzato le caratteristiche clinico-patologiche di 60 pazienti affetti da carcinoma mammario maschile trattati presso la nostra unità di radioterapia in un periodo compreso tra il 1971 ed il 2011. Le neoplasie sono state classificate in accordo con la variante istologica e la classificazione aggiornata TNM 2010 dei tumori maligni.RisultatiAd un follow-up mediano di 8,9 anni [range 0,6–20; deviazione standard (SD) 4,98], 32 pazienti (53,3%) risultano viventi, mentre 16 (26,7%) sono deceduti a causa della malattia e 12 (20%) per altre cause. All’analisi univariata per sopravvivenza assoluta, le dimensioni patologiche del tumore (p=0,031), l’istologia (p=0,013) e lo stato linfonodale (p=0,006) sono emersi quali significativi predittori di morte. All’analisi multivariata, risultano fattori prognostici indipendenti le maggiori dimensioni patologiche del tumore (p=0,016), lo stato linfonodale positivo (p=0,003) e l’istologia cribriforme invasiva (p=0,0003).ConclusioniIn considerazione della rarità della patologia, molti sono i temi ancora dibattuti e necessitano futuri studi collaborativi. La nostra esperienza conferma tuttavia l’impatto prognostico sfavorevole delle dimensioni patologiche del tumore e dello stato linfonodale positivo.Purpose. We conducted a retrospective analysis to evaluate the management and outcome of invasive male breast cancer treated in a single-institution over a period of 40 years. Materials and methods. We reviewed the clinical and pathological features of 60 male patients affected by breast carcinoma treated at our Radiotherapy Unit between 1971 and 2011. Tumours were classified according to histological type and the updated 2010 TNM classification of malignant tumours. Results. At a median follow-up of 8.9 [range, 0.6–20; standard deviation (SD), 4.98] years, 32 patients (53.3%) were alive and 16 patients died (26.7%) due to disease progression and 12 (20%) due to other causes. At univariate analysis for overall survival, pathological tumour size (p=0.031), histological subtype (p=0.013) and nodal status (p=0.006) emerged as significant predictors of death. At multivariate analysis, independent death predictors were advanced pathological tumour size (p=0.016), positive nodal status (p=0.003) and invasive cribriform histological type (p=0.0003). Conclusions. In consideration of the rarity of the disease, many issues are still being debated, and future collaborative studies are required. However, our experience confirms the prognostic role of greater Riassunto Obiettivo. Abbiamo condotto un’analisi retrospettiva per valutare il trattamento e la sopravvivenza di una serie di pazienti affetti da carcinoma mammario invasivo maschile trattati in un singolo centro in un periodo di 40 anni. Materiali e metodi. Abbiamo analizzato le caratteristiche clinico-patologiche di 60 pazienti affetti da carcinoma mammario maschile trattati presso la nostra unità di radioterapia in un periodo compreso tra il 1971 ed il 2011. Le neoplasie sono state classificate in accordo con la variante istologica e la classificazione aggiornata TNM 2010 dei tumori maligni. Risultati. Ad un follow-up mediano di 8,9 anni [range 0,6– 20; deviazione standard (SD) 4,98], 32 pazienti (53,3%) risultano viventi, mentre 16 (26,7%) sono deceduti a causa della malattia e 12 (20%) per altre cause. All’analisi univariata per sopravvivenza assoluta, le dimensioni patologiche del tumore (p=0,031), l’istologia (p=0,013) e lo stato linfonodale (p=0,006) sono emersi quali significativi predittori di morte. All’analisi multivariata, risultano fattori prognostici indipendenti le maggiori dimensioni patologiche del tumore (p=0,016), lo stato linfonodale positivo (p=0,003) e l’istologia cribriforme invasiva (p=0,0003). Conclusioni. In considerazione della rarità della patologia, molti sono i temi ancora dibattuti e necessitano RADIOTHERAPY RADIOTERAPIA Treatment of invasive male breast cancer: a 40-year single-institution experience Il trattamento del carcinoma mammario invasivo maschile: 40 anni di esperienza in un singolo centro I. Meattini1 • L. Livi1 • D. Franceschini1 • C. Saieva2 • V. Scotti1 • D. Casella3 • V. Criscenti3 I. Zanna2 • F. Meacci1 • E. Gerlain2 • B. Agresti1 • M. Mangoni1 • F. Paiar1 • G. Simontacchi1 D. Greto1 • J. Nori4 • S. Bianchi5 • L. Cataliotti3 • G. Biti1 Radiotherapy Unit, Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy Molecular and Nutritional Epidemiology Unit, ISPO (Cancer Research and Prevention Institute), University of Florence, Florence, Italy Department of Surgery, Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy Diagnostic Senology Unit, Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy Division of Pathological Anatomy, Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy Correspondence to: Icro Meattini, Radiotherapy Unit, University of Florence, Largo G.A. Brambilla 3, 50134 Florence, Italy Tel.: +39-055-7947719, Fax: +39-055-4379930, e-mail: icro.meattini@unifi.it Received: 9 October 2011 / Accepted: 4 December 2011 / Published online: 9 August 2012