Patrizia Ciammella

Stereotactic body radiation therapy for early stage non-small cell lung cancer: Results of a prospective trial

Patients affected with early stage (IA-IB) non-small cell lung cancer (NSCLC), deemed medically inoperable, are usually treated by conventional 3D-CRT, with poor results in terms of local tumour control and survival. Hypofractionated stereotactic body radiation therapy (SBRT) appears to be a valid alternative option, with high rates of local control and promising survival rates according to recent reported series. We herein report the final results of a prospective phase II trial of SBRT in 62 stage I NSCLC patients, homogeneously treated with three fractions of 15Gy each, given every other day during a 1 week time, up to a total dose of 45Gy; dose was prescribed to the 80%-isodose encompassing planning target volume. Patients were immobilized in a dedicated stereotactic body frame; margins around gross tumour volume were 5mm in the axial plane and 10mm in the longitudinal direction. Median age was 73.7 years. A pathologic confirmation of NSCLC was obtained in 64.5% of patients. Forty-three patients had stage IA and 19 stage IB disease. The majority of patients did not experience any toxicity; mild skin reactions, fatigue, dyspnea/cough or transient thoracic pain were recorded in approximately 10% of patients. With a median follow-up time of 28 months, 2 patients experienced an isolated local relapse, 4 an isolated nodal relapse and 15 a systemic failure. At 3 years, local control rate was 87.8%, cancer-specific survival 72.5%, overall survival 57.1%, with 8 out of 20 non-cancer related deaths. In multivariate analysis, tumour volume was associated with a better outcome. In our series, SBRT was well tolerated and confirmed its efficacy, with local control and survival rates globally superior to those reported using conventional radiotherapy. A longer follow-up is needed in order to establish a correct comparison with surgical series, and to fully ascertain a potential negative impact of SBRT on comorbidities of such a fragile patients population.

Stereotactic body radiation therapy for lung metastases

INTRODUCTION Stereotactic body radiation therapy (SBRT) has an emerging role in patients affected with pulmonary metastases. Purpose of this study was to evaluate efficacy and tolerability of SBRT in a cohort of patients treated between 2003 and 2009 at our institution. METHODS A total of 61 patients with oligometastatic lung tumors (single pulmonary nodules in 73.7%) were included in the study. SBRT was performed with a stereotactic body frame and a 3D-conformal technique. Fifty-one patients received 26 Gy in 1 fraction, 22 a dose of 45 Gy in 3 fractions and 3 a dose of 36 Gy in 4 fractions. Primary tumor was lung cancer in 45.7% of patients, colorectal cancer in 21.3% and a variety of other origins in 33%. The primary endpoint was local control, secondary endpoints were survival and toxicity. RESULTS After a median follow-up interval of 20.4 months, local control rates at 2 and 3 years were 89% and 83.5%, overall survival 66.5% and 52.5%, cancer-specific survival 75.4% and 67%, progression-free survival 32.4% and 22.3%. Tumor volume was significantly associated to survival, with highest rates in patients with single small tumors. Median survival time was 42.8 months, while median progression-free survival time was 11.9 months. Toxicity profiles were good, with just one case of grade III toxicity (pneumonitis). CONCLUSION This study shows that SBRT is an effective and safe local treatment option for patients with lung metastases. Definitive results are strictly correlated to clinical selection of patients.

Different IMRT solutions vs. 3D-Conformal Radiotherapy in early stage Hodgkin's lymphoma: dosimetric comparison and clinical considerations

BackgroundRadiotherapy in Hodgkin’s Lymphoma (HL) is currently evolving with new attempts to further reduce radiation volumes to the involved-node concept (Involved Nodes Radiation Therapy, INRT) and with the use of intensity modulated radiotherapy (IMRT). Currently, IMRT can be planned and delivered with several techniques, and its role is not completely clear. We designed a planning study on a typical dataset drawn from clinical routine with the aim of comparing different IMRT solutions in terms of plan quality and treatment delivery efficiency.MethodsA total of 10 young female patients affected with early stage mediastinal HL and treated with 30 Gy INRT after ABVD-based chemotherapy were selected from our database. Five different treatment techniques were compared: 3D-CRT, VMAT (single arc), B-VMAT (“butterfly”, multiple arcs), Helical Tomotherapy (HT) and Tomodirect (TD). Beam energy was 6 MV, and all IMRT planning solutions were optimized by inverse planning with specific dose-volume constraints on OAR (breasts, lungs, thyroid gland, coronary ostia, heart). Dose-Volume Histograms (DVHs) and Conformity Number (CN) were calculated and then compared, both for target and OAR by a statistical analysis (Wilcoxon’s Test).ResultsPTV coverage was reached for all plans (V95% ≥ 95%); highest mean CN were obtained with HT (0.77) and VMAT (0.76). B-VMAT showed intermediate CN mean values (0.67), while the lowest CN were obtained with TD (0.30) and 3D-CRT techniques (0.30). A trend of inverse correlation between higher CN and larger healthy tissues volumes receiving low radiation doses was shown for lungs and breasts. For thyroid gland and heart/coronary ostia, HT, VMAT and B-VMAT techniques allowed a better sparing in terms of both Dmean and volumes receiving intermediate-high doses compared to 3D-CRT and TD.ConclusionsIMRT techniques showed superior target coverage and OAR sparing, with, as an expected consequence, larger volumes of healthy tissues (lungs, breasts) receiving low doses. Among the different IMRT techniques, HT and VMAT showed higher levels of conformation; B-VMAT and HT emerged as the planning solutions able to achieve the most balanced compromise between higher conformation around the target and smaller volumes of OAR exposed to lower doses (typical of 3D-CRT).

Involved-Site Image-Guided Intensity Modulated Versus 3D Conformal Radiation Therapy in Early Stage Supradiaphragmatic Hodgkin Lymphoma

PURPOSE Image-guided intensity modulated radiation therapy (IG-IMRT) allows for margin reduction and highly conformal dose distribution, with consistent advantages in sparing of normal tissues. The purpose of this retrospective study was to compare involved-site IG-IMRT with involved-site 3D conformal RT (3D-CRT) in the treatment of early stage Hodgkin lymphoma (HL) involving the mediastinum, with efficacy and toxicity as primary clinical endpoints. METHODS AND MATERIALS We analyzed 90 stage IIA HL patients treated with either involved-site 3D-CRT or IG-IMRT between 2005 and 2012 in 2 different institutions. Inclusion criteria were favorable or unfavorable disease (according to European Organization for Research and Treatment of Cancer criteria), complete response after 3 to 4 cycles of an adriamycin- bleomycin-vinblastine-dacarbazine (ABVD) regimen plus 30 Gy as total radiation dose. Exclusion criteria were chemotherapy other than ABVD, partial response after ABVD, total radiation dose other than 30 Gy. Clinical endpoints were relapse-free survival (RFS) and acute toxicity. RESULTS Forty-nine patients were treated with 3D-CRT (54.4%) and 41 with IG-IMRT (45.6%). Median follow-up time was 54.2 months for 3D-CRT and 24.1 months for IG-IMRT. No differences in RFS were observed between the 2 groups, with 1 relapse each. Three-year RFS was 98.7% for 3D-CRT and 100% for IG-IMRT. Grade 2 toxicity events, mainly mucositis, were recorded in 32.7% of 3D-CRT patients (16 of 49) and in 9.8% of IG-IMRT patients (4 of 41). IG-IMRT was significantly associated with a lower incidence of grade 2 acute toxicity (P=.043). CONCLUSIONS RFS rates at 3 years were extremely high in both groups, albeit the median follow-up time is different. Acute tolerance profiles were better for IG-IMRT than for 3D-CRT. Our preliminary results support the clinical safety and efficacy of advanced RT planning and delivery techniques in patients affected with early stage HL, achieving complete response after ABVD-based chemotherapy.

Efficacy and Safety of Tadalafil 20 mg on Demand vs. Tadalafil 5 mg Once-a-Day in the Treatment of Post-Radiotherapy Erectile Dysfunction in Prostate Cancer Men: A Randomized Phase II Trial

INTRODUCTION The role of phosphodiesterase type 5 inhibitors in the treatment of post-radiotherapy erectile dysfunction (ED) has not been extensively investigated. AIM To compare the efficacy and safety of on-demand 20-mg tadalafil (arm A) with the newly released tadalafil 5-mg once-a-day dosing (arm B) in patients with ED following radiotherapy for prostate cancer (PC). METHODS Randomized study to receive on-demand 20-mg or once-a-day 5-mg tadalafil for 12 weeks. Main Outcome Measures.  Changes in the International Index of Erectile Function (IIEF) domain scores and Sexual Encounter Profile (SEP) question 2 and 3 positive response rates. RESULTS Fifty-two out of 86 screened patients were randomized. Forty-four patients were evaluable for efficacy. A significant improvement in all domains of the IIEF was observed in both arms (P = 0.0001) with mean erectile function domain scores values of 25 and 27.1 for the 20-mg and 5-mg tadalafil, respectively (P = 0.19). SEP 2 and 3 positive response rates increased from 0% in both arms at baseline to 81% and 70% in the 20-mg arm and 90% and 73% in the 5-mg arm, respectively, at the end of treatment (P = 0.27). End of treatment global efficacy question positive answers were 86% in the 20-mg arm and 95% in the 5-mg arm (P = 0.27). Higher treatment compliance was shown in arm B (100%) as compared with arm A (86%). There was a nonstatistically significant trend toward fewer side effects in favor of the 5-mg daily dose arm. CONCLUSIONS In the study population, both tadalafil formulations generated significantly high response rates according to the outcome measures and were well tolerated. The once-a-day 5-mg dosing showed higher compliance and marginally reduced side effects, thus making it an attractive alternative to on-demand therapy for ED in post-radiotherapy PC patients.

Hypofractionated stereotactic radiation therapy for recurrent glioblastoma: single institutional experience

BackgroundGlioblastoma (GBM) is the most common malignant primary brain tumor in adults. Tumor control and survival have improved with the use of radiotherapy (RT) plus concomitant and adjuvant chemotherapy, but the prognosis remain poor. In most cases the recurrence occurs within 7–9 months after primary treatment. Currently, many approaches are available for the salvage treatment of patients with recurrent GBM, including resection, re-irradiation or systemic agents, but no standard of care exists.MethodsWe analysed a cohort of patients with recurrent GBM treated with frame-less hypofractionated stereotactic radiation therapy with a total dose of 25 Gy in 5 fractions.ResultsOf 91 consecutive patients with newly diagnosed GBM treated between 2007 and 2012 with conventional adjuvant chemo-radiation therapy, 15 underwent salvage RT at recurrence. The median time interval between primary RT and salvage RT was 10.8 months (range, 6–54 months). Overall, patients undergoing salvage RT showed a longer survival, with a median survival of 33 vs. 9.9 months (p= 0.00149). Median overall survival (OS) from salvage RT was 9.5 months. No patients demonstrated clinically significant acute morbidity, and all patients were able to complete the prescribed radiation therapy without interruption.ConclusionOur results suggest that hypofractionated stereotactic radiation therapy is effective and safe in recurrent GBM. However, until prospective randomized trials will confirm these results, the decision for salvage treatment should remain individual and based on a multidisciplinary evaluation of each patient.

The “PROCAINA (PROstate CAncer INdication Attitudes) Project” (Part II) — A survey among Italian radiation oncologists on radical radiotherapy in prostate cancer

PurposeRadiotherapy (RT) has an established role in the treatment of prostate cancer patients. Despite the large number of patients treated with RT, some issues about optimal techniques, doses, volumes, timing, and association with androgen deprivation are still subject of debate. The aim of this survey was to determine the patterns of choice of Italian radiation oncologists in two different clinical cases of prostate cancer patients treated with radical RT.Study designDuring the 2010 Italian Association of Radiation Oncology (AIRO) National congress, four different clinical cases were presented to attending radiation oncologists. Two of them were prostate cancer cases that could be treated by RT +/− hormonal therapy (HT), different for T stage of primary tumour according to TNM, preoperative diagnostic procedures for staging, initial prostate specific antigen (iPSA), and Gleason Score sum of biopsy. For each clinical case, radiation oncologists were asked to: (a) give indication to pretreatment procedures for staging; (b) give indication to treatment; (c) define specifically, where indicated, total dose, type of fractionation, volumes of treatment, type of technique, type of image-guided setup control; (d) indicate if HT should be prescribed; (e) define criteria that particularly influenced prescription. A descriptive statistical analysis was performed.ResultsThree hundred questionnaires were given to radiation oncologists attending the congress, 128 questionnaires were completed and considered for this analysis (41%). Some important differences were shown in prescribing and delivering RT, particularly with regards to treatment volumes and fractionation.ConclusionsDespite the results of clinical trials, several differences still exist among Italian radiation oncologists in the treatment of prostate cancer patients. These patients probably deserve a more uniform approach, based on upto-date, detailed, and evidence-based recommendations.RiassuntoObiettivoLa radioterapia (RT) ricopre un ruolo ben stabilito nel trattamento dei pazienti con tumore della prostata. Nonostante il grande numero di pazienti trattati con RT, alcune controversie circa la tecnica ottimale di trattamento, le dosi, i volumi, il timing rispetto alla chirurgia e l’associazione con la terapia ormonale sono ancora oggetto di dibattito. Lo scopo di questa indagine è stato di determinare la modalità di scelta di trattamento degli oncologi radioterapisti italiani in 2 diversi casi clinici di pazienti affetti da tumore prostatico trattati con RT a scopo radicale.Disegno di studioDurante il Congresso Nazionale dell’Associazione Italiana di Radioterapia Oncologica (AIRO) del 2010, 4 casi clinici sono stati proposti agli oncologi radioterapisti presenti. Due di questi casi clinici si presentavano adeguati alla RT a scopo radicale +/− ormonoterapia (OT), ed erano diversi per stadio clinico, procedure diagnostiche di staging pre-trattamento, antigene specifico della prostata (PSA) iniziale, Gleason Score bioptico. Per ogni caso clinico si chiedeva di (a) dare indicazione a nuove procedure di staging pre-trattamento; (b) dare indicazione al trattamento; (c) definire in particolare, se indicato, la dose totale, il tipo di frazionamento, i volumi di trattamento, il tipo di tecnica, il tipo di controllo del set-up guidato dalle immagini; (d) dare indicazione a un trattamento ormonale eventuale; (e) definire i criteri maggiormente influenzanti la prescrizione. è stata eseguita un’analisi descrittiva delle risposte.RisultatiTrecento questionari sono stati consegnati agli oncologi radioterapisti partecipanti; 128 sono stati correttamente compilati e considerati per questa analisi (41%). Alcune importanti differenze sono state messe in evidenza nella prescrizione e nell’erogazione della RT, particolarmente riguardanti i volumi di trattamento e il frazionamento della dose. Sono state evidenziate alcune differenze con le raccomandazioni internazionali e i dati disponibili in letteratura sono stati rivisti e discussi.ConclusioniConclusioniNonostante i risultati di diversi studi clinici, persistono alcune differenze significative tra gli oncologi radioterapisti italiani nel trattamento dei pazienti con tumore prostatico. Questi pazienti meriterebbero un approccio più uniforme basato su raccomandazioni aggiornate, dettagliate e condivise sulla base delle evidenze disponibili.

The “BUONGIORNO” Project: Burnout Syndrome Among Young Italian Radiation Oncologists

Few data exist about the prevalence of burnout syndrome among young radiation oncologists. A national survey to assess its prevalence among junior members (under 40 yrs of age) of the Italian Society of Radiation Oncology was conducted. One hundred and twelve young radiation oncologists completed the questionnaire: the prevalence of burnout syndrome was 35%, and it was related to the presence of different personal, organizational, and work-related aspects, with an impact also on the private life (p < .005). Burnout syndrome is relatively common among young Italian radiation oncologists, and specific educational tools to help improve the management of workload and stress are needed.

Squamous cell carcinoma of the prostate: long-term survival after combined chemo-radiation

BackgroundCarcinoma of the prostate gland is the most frequent malignant tumour affecting male population. While the large majority of tumours is represented by adenocarcinoma, pure squamous cell carcinoma comprises only 0,5–1% of all prostate neoplastic lesions.It is characterised by a high degree of malignancy, commonly metastasising to the bone (mainly with osteolytic lesions), liver and lungs with a median survival time of 14 months.Several therapeutic approaches have been employed in the effort to treat prostate pure squamous cell carcinoma, including radical surgery, radiotherapy, chemotherapy and hormonal therapy. All of them mostly failed to gain a significant survival benefit.Case reportWe herein report on a case of pure squamous cell carcinoma of the prostate approached with combined-modality treatment, with the administration of 3 courses of cisplatin 75 mg/m2 on day 1 and continous infusion 5-fluorouracil 750 mg/m2 on day 1 to 5 and, subsequently, radiotherapy, with the delivery of a total dose of 46 Gy to the whole pelvis, with additional boost doses of 20 Gy to the prostatic bed and adjunctive 6 Gy to the prostate gland (72 Gy in total). The patient remained free of disease for 5 years, finally experiencing local relapse and, subsequently, dying of acute renal failure due to bilateral uretero-hydro-nephrosis.In addition, we provide a complete overview of all reported cases available within the medical literature.ConclusionSince it remains questionable which should be the most appropriate therapeutic approach towards prostate pure squamous cell carcinoma, our report demonstrates that a prolonged disease control, with a consistent survival time, may be achieved by the combination of an effective local treatment such as radiotherapy with systemic infusion of chemotherapeutic drugs.

Prostate cancer as a paradigm of multidisciplinary approach? Highlights from the Italian young radiation oncologist meeting

AIMS AND BACKGROUND The diagnostic and therapeutic approach to prostate cancer has evolved rapidly in last decades. Young professionals need an update about these recent developments in order to improve the care of patients treated in their daily clinical practice. METHODS On May 18, 2013, AIRO Giovani (the young section of the Italian Association of Radiation Oncology) organized a multidisciplinary meeting involving, as speakers, several young physicians from many parts of Italy actively involved in the diagnostic and therapeutic approach to prostate cancer. The meeting was specifically addressed to young physicians (radio-oncologists, urologists, medical oncologists) and presented the state-of-the-art of the diagnostic/therapeutic approach based on the latest evidence on the issue. Highlights of the congress are summarized and presented in this report. RESULTS The large participation in the meeting (more than 120 participants were present) confirmed the interest of young radiation oncologists in improving their skills in prostate cancer management. The contributions of the speakers confirmed the need for regular updates, considering the promising results of recently published studies and the many new ongoing trials, on the diagnostic and therapeutic approaches to prostate cancer. CONCLUSIONS Multidisciplinary meetings are helpful to improve the skills of young professionals.