F. Meacci

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.

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.

Overview on cardiac, pulmonary and cutaneous toxicity in patients treated with adjuvant radiotherapy for breast cancer

Conservative management of breast cancer represents the standard treatment for early disease. Breast conserving surgery associated with radiotherapy for stage I-II has been proven to be as equally effective as mastectomy in term of local control, distant disease, and overall survival. The growing minimal invasive surgical approach on the axillary region, and the new breast reconstructive techniques, will probably lead to a significant decrease of the rate of side-effects related to mastectomy. Therefore, the adverse events caused by adjuvant radiation still remain a challenge. Cutaneous, pulmonary and cardiac toxicity represent the main toxicities of adjuvant radiotherapy for breast cancer. Safety profile of radiation is strongly dependent on the multidisciplinary management of the single case (systemic treatment, endocrine therapy, surgery), individual characteristics (i.e., co-morbidities, age, habits), and radiation-related aspects. Radiation techniques development, and facilities implementation concerning organs-at-risk sparing systems (i.e., image-guided radiotherapy, tracking systems, respiratory gating), represent brand new tools for the clinical oncologist, that would certainly minimize toxicity profile in the next future. However, data reported from published literature will greatly help physicians, to give to the patients appropriate counseling regarding the efficacy and potential adverse events of treatments, thus optimizing the informed decision-making process.

Impact of age on cytotoxic-induced ovarian failure in breast cancer treated with adjuvant chemotherapy and triptorelin

AIM This study analyzes our single-center, retrospective experience on 63 premenopausal breast cancer patients treated with monthly triptorelin and concomitant chemotherapy. PATIENTS & METHODS Concomitant chemotherapy and triptorelin were adopted as part of premature ovarian failure prevention strategy. RESULTS Age at diagnosis was the main factor influencing fertility preservation (p = 0.002). Compared with patients aged 41-45 years, the probability of menses resumption was almost threefold than for women aged 35-40 years, and significantly higher for women aged <35 years (hazard ratio: 9.0; p = 0.0001). The cumulative proportion among patients who resumed menses was 33.3% at 6 months, 75% at 12 months and 87.5% at 24 months. Seven patients attempted pregnancy, and five (71%) obtained healthy deliveries. CONCLUSION We observed an acceptable rate of fertility preservation. Age at diagnosis influences fertility preservation.

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

Prognostic factors in patients with locally advanced head and neck cancer treated with concurrent radiochemotherapy

PurposeThis study was undertaken to evaluate the association of individual parameters and outcome in patients with unresectable locally advanced head and neck cancer treated with radiochemotherapy.Materials and methodsWe retrospectively reviewed data from 126 patients treated in our Institution between 1998 and 2010 for a locally advanced head and neck cancer. Sixteen individual parameters were evaluated for association with specific outcomes such as overall survival, persistence of disease, disease-specific survival and disease-free survival.ResultsSix factors influenced overall survival on Kaplan–Meier survival analysis and on univariate Cox regression analysis: smoking, body mass index, site, haemoglobin (Hb) nadir, total dose of radiotherapy and comorbidities. On a multivariate logistic model with stepwise selection, comorbidities, body mass index, total dose and site maintained significance. A significant association for persistence of disease was found with smoking, Hb nadir and site of cancer on univariate and multivariate analysis. Disease-free survival was correlated with performance status, Hb nadir and comorbidities using Kaplan–Meier survival analysis and on univariate Cox regression analysis. Only performance status maintained the significance on multivariate analysis. Disease-specific survival was correlated with five parameters: body mass index, site, Hb nadir, therapy interruption and total dose; on multivariate analysis, Hb nadir, therapy interruption and site maintained a statistically significant association.ConclusionsHb nadir during treatment, body mass index, smoking, stage, comorbidities and performance status are prognostic factors of outcome and response to radical treatment with radiochemotherapy.

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.

Nivolumab Induced Hemolitic Anemia in Patient with Advanced Squamous Cell Lung Cancer (SCC)

Nivolumab, a humanized IgG4 programmed death-1 (PD-1) inhibitor antibody, is approved in Italy for advanced non small cell lung cancer (NSCLC), for advanced melanoma in association with ipilimumab, in second line renal cell carcinoma (RCC), in Hodgkin lymphoma relapsed after autologous stem cell transplantation and treatment with brentuximab vedotin, in head and neck squamous cell carcinoma progressed after platinum therapy and in locally advanced urothelial carcinoma unresectable or metastatic after failure of previous platinum therapy. Its immunogenic potential is well known, with described autoimmune-like syndromes, but no clear association is evident for hemolytic anemia. We report case of a 68-year-old man who developed hemolytic anemia after 28 cycles of treatment for advanced Squamous Cell Lung Cancer (SSC).

Abstract P1-10-04: Accelerated partial breast irradiation versus whole breast irradiation: Health-related quality of life analysis from a phase 3 trial

Background. Accelerated partial breast irradiation (APBI) represents a valid option for selected early breast cancer (BC); potential advantages of APBI include shorter treatment time, improved safety profile, and a cost reduction compared with standard fractionation. We reported the final analysis of quality of life (QOL) results from a phase 3 randomized trial comparing standard adjuvant radiotherapy (50 Gy in 25 fractions, plus 10 Gy boost) to APBI using IMRT technique (30 Gy in 5 daily fractions). The 5-year results have been recently published showing equivalence in terms of local control (ClinicalTrials.gov, NCT02104895). Methods. Overall 205 patients (105 APBI and 100 WBI) fully completed the given questionnaires at time 0 (RT start), time 1 (RT end), and time 2 (2-year follow up). Patients were asked to compile two specific questionnaires on QOL, the EORTC QLQ-C30 as a reliable and valid measure of the QOL of cancer patients in multicultural clinical research settings, and the BR23 module as a supplementary questionnaire for assessing QOL issues relevant to patients with BC. The statistical software SPSS (SPSS Inc, Chicago, IL, USA) for Windows (version 22), and STATA (StataCorp LP, College Station TX77845, USA) for Windows (version 12) were used. Chi-squared test or Mann Whitney U test were used to compare the individual characteristics of the patients between two arms. Mean and standard deviations (SD) were calculated for all QOL domains, and all scores were compared between APBI and WBI arms using the Mann Whitney test due to non-parametric distribution of data. The Kruskal-Wallis test was used to compare the scores between age groups. Results. Mean values (and SD) of QLQ-C30 scores according to arm in the series of 205 BC patients at time 2 (time 0 vs time 2), showed significant improvement in favor of APBI in terms of global health status (mean 75.5 vs 59.5, SD range 13.3-22.0; p Conclusions. Women treated with APBI reported a significantly better QOL outcome as compared with women treated using WBI. QOL improvement was evidenced in terms of functional, symptoms, and global health status/QOL scales, both at the end of radiation and at a 2-year follow-up time. Citation Format: Meattini I, Saieva C, Desideri I, Miccinesi G, Francolini G, Meacci F, Muntoni C, Scotti V, De Luca Cardillo C, Marrazzo L, Simontacchi G, Pallotta S, Sanchez L, Casella D, Bernini M, Orzalesi L, Nori J, Bianchi S, Livi L. Accelerated partial breast irradiation versus whole breast irradiation: Health-related quality of life analysis from a phase 3 trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-10-04.

EP-1665: Scalp-Sparing focal radiotherapy for gliomas using VMAT or Helical Tomotherapy: a feasibility study

Purpose or Objective: Both transient and permanent alopecia have a huge psychological impact on patient’s quality of life. Sparing the scalp during focal cranial RT for gliomas is a challenging issue during the treatment planning process due to the fact that the scalp is often strictly adjacent to the cortical or subcortical target. In addition, clear constraints for this structure to be used during the inverse planning are not available in literature, most of them being very strict. We report our preliminary experience with scalp sparing technique for patients with high grade gliomas.