Angela Botticella

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).

Predictive parameters of symptomatic radiation pneumonitis following stereotactic or hypofractionated radiotherapy delivered using volumetric modulated arcs.

PURPOSE To identify dosimetric factors that predict development of radiation pneumonitis (RP) following stereotactic or hypofractionated radiotherapy for lung tumors. METHODS Seventy-nine consecutive patients with either a planning target volume (PTV)>100 cm(3) (n=69) or prior pneumonectomy or bi-lobectomy (n=13) were identified. Radiation doses (range: 5-50 Gy, with 5 Gy increments) were converted to equivalent doses (EQD(2 Gy)) (α/β=3). Total lung (TL), ipsilateral (IL) and contralateral lung (CL) volumes minus PTV, receiving 5 Gy (V5) up to 50 Gy (V50) and mean lung dose (MLD) were analyzed. Predictors of grade ≥3 RP (CTCAEv4.03) were identified with concordance-statistics (C-statistic) and p-values used to quantify the performance of the model. Factors found to be significant were entered into a recursive partitioning analysis (RPA). RESULTS Median PTV was 150 cm(3). Grade ≥3 RP was observed in 8 patients (10%). In univariable analysis, CL-MLD, CL-V5-15, TL-MLD, TL-V5-V10 and ITV size were predictive of RP (p<0.05). In multivariable analysis, contralateral MLD (p=.007) and ITV (p=.063) were the strongest predictors of grade ≥3 RP, with excellent discrimination (C-statistic: 0.868). CONCLUSION Contralateral MLD and ITV size are both strong predictors of grade ≥3 RP post treatment. Planning constraints should aim to keep contralateral MLD below 3.6 Gy.

Interim positron emission tomography and clinical outcome in patients with early stage Hodgkin lymphoma treated with combined modality therapy

Abstract The aim of the study was to investigate whether interim positron emission tomography (iPET) is prognostic in a cohort of patients with early stage Hodgkin lymphoma (HL) homogeneously treated with 3–4 cycles of ABVD (adriamycin, bleomycin, vinblastine and dacarbazine) followed by 30 Gy involved field radiotherapy. Eighty patients were selected (stage I–IIA HL, availability of iPET, minimum follow-up of 12 months), and after central review, 70 were judged negative (iPET−: 87.5%) and 10 positive (iPET+: 12.5%). The two groups were then analyzed for response, progression-free survival (PFS) and overall survival (OS). Only one out of 70 iPET− patients relapsed, with 69 in continuous complete remission (CCR). All 10 iPET + patients achieved a complete response and maintained persistent CCR at follow-up. The 3-year PFS and OS were, respectively, 97% and 98.4% for iPET− and 100% and 100% for iPET+ (p = 0.63). iPET positivity does not seem to be a significant prognostic factor, and change in therapeutic strategy on the basis of iPET does not appear currently advisable outside clinical trials.

Changes in breast cancer risk associated with different volumes, doses, and techniques in female Hodgkin lymphoma patients treated with supra-diaphragmatic radiation therapy

PURPOSE The contribution of thoracic radiation in increasing secondary breast cancer (BC) risk in female Hodgkin lymphoma patients is well known, and recent changes in radiation therapy volumes, doses and techniques are supposed to minimize it. In this study, we compared different radiation therapy solutions in terms of secondary BC induction risk with the aim of selecting which could be considered the most protective. METHODS AND MATERIALS In 10 female patients under 30 years old we estimated breast cancer risk for different combined treatment solutions (involved field vs involved nodal radiation therapy [IFRT vs INRT], 30 Gy vs 20 Gy, 3-dimensional conformal radiation therapy vs volumetric modulated arc therapy [3DCRT vs VMAT]). The organ equivalent dose (OED) method was used for dose calculation, as OED is directly related to the excess risk. Estimated OED mean values for all options in all patients were then analyzed and compared. RESULTS INRT was significantly associated with a lower OED, regardless of total dose and technique (0.43 vs 1.15, P < .0001). The relative OED reduction from IFRT to INRT was approximately 60%. The dose of 20 Gy resulted in a significant reduction of OED, approximately 25% (0.68 vs 0.9, P < .01). VMAT did not show significantly higher OED when compared with 3DCRT (0.84 vs 0.74, P = .15). The combination of INRT and 20 Gy lead to a decrease in OED of approximately 70% if compared with IFRT 30 Gy. CONCLUSIONS The INRT approach substantially reduces OED, independent of dose and technique; the dose reduction from 30 Gy to 20 Gy also has a significant impact, and as expected INRT-20 Gy resulted to be the solution at lowest risk. No differences were observed when comparing different techniques (3DCRT vs VMAT). The combination of these innovative approaches might lead to a substantial reduction in secondary breast cancer risk in this patient population.

125I brachytherapy for localized prostate cancer: a single institution experience.

AIMS AND BACKGROUND To evaluate the clinical outcome of a cohort of localized prostate cancer patients treated with 125I permanent brachytherapy at the University of Turin. METHODS AND STUDY DESIGN A retrospective analysis was carried out on 167 consecutive patients with early stage prostate adenocarcinoma who underwent 125I brachytherapy between January 2003 and December 2010. A minimum follow-up of ≥ 12 months was mandatory for inclusion. Biochemical disease-free survival (defined on the basis of the ASTRO definition and the ASTRO-Phoenix definition) was chosen as the primary end point. Secondary end points were gastrointestinal and genitourinary toxicity (acute and late, defined according to the RTOG scale). RESULTS With a median follow-up of 42 months (range, 13.5-90.7), biochemical disease-free survival at 3 and 5 years was respectively 91.1% and 85.7%, according to the ASTRO definition and 94.5% and 85.1% according to ASTRO-Phoenix definition (for statistical purposes, only the ASTRO definition was used). Hormone treatment and nadir PSA (cutoff of 0.35 ng/ml) were the only factors affecting biochemical disease-free survival both on univariate (P = 0.02 and P = 0.001, respectively) and multivariate analysis (HR 0.024; P = 0.021 and HR 21.6; P = 0.006, respectively). Only 3.6% of patients experienced ≥ grade 3 acute urinary toxicity and 5% ≥ grade 3 late urinary toxicity. Prior transurethral prostate resection was the only independent predictor of grade 3 late urinary toxicity on multivariate analysis (HR 0.13; P = 0.009). CONCLUSIONS This mono-institutional series confirmed that brachytherapy is an effective and safe treatment modality for localized prostate cancer, with acceptable short- and long-term morbidity rates.

Polyostotic sclerosing histiocytosis (Erdheim-Chester disease) treated with combined vertebroplasty and radiation therapy

Erdheim-Chester disease is an uncommon form of non-Langherans-cell histiocytosis, with a heterogeneous range of systemic manifestations and a pattern of typical clinico-pathological and radiological features. Symmetric sclerotic radiological alterations of the long bones are peculiar, such as the infiltration of several organs by lipid-laden histiocytes. Radiation therapy has been anecdotally employed in a palliative setting in order to relieve symptoms mainly due to cerebral, retro-orbital and skeletal localizations. Exclusive osseous involvement is rarely described in the medical literature. Moreover, the role, timing and schedule of radiotherapy in this subset of patients remain controversial. We herein report on a case of osseous-only Erdheim-Chester disease treated with a combined modality approach including transoral vertebroplasty and external beam radiation therapy, which gave an analgesic effect that lasted 1 year, with no treatment-related side effects.

Salvage External Beam Radiotherapy for Recurrent Prostate Adenocarcinoma after High-Intensity Focused Ultrasound as Primary Treatment

Introduction: The main objective was to evaluate feasibility, toxicity and biochemical control rates of salvage external beam radiotherapy (EBRT) in recurrent localized prostate cancer after high-intensity focused ultrasound (HIFU) as primary therapy. Patients and Methods: A total of 24 patients who underwent salvage EBRT after 1 or 2 HIFU sessions and with a minimum post-treatment follow-up of 24 months were retrospectively evaluated. Primary endpoints were toxicity and biochemical disease-free survival (bDFS, defined according to the ASTRO Phoenix definition). Results: Median follow-up was 40.3 months. Gastrointestinal toxicity was low. Acute genitourinary (GU) toxicity grade ≤II rate was 45.8%, with only few patients presenting grade III (8.3%) and grade IV (4.2%) toxicity. Late grade ≥III GU toxicity was registered in 16.7% of patients. The 3-year bDFS rate was 77.8%. Patients achieving a nadir prostate-specific antigen (nPSA) of ≤0.35 ng/ml after EBRT had significantly higher bDFS (3-year bDFS: 87.7 vs. 50%, respectively; p = 0.001). Achieving nPSA ≤0.35 ng/ml was the only factor independently associated to long-term bDFS both on univariate (p = 0.01) and multivariate analysis (HR 7.06, p = 0.039). Conclusions: Salvage EBRT after HIFU failure is feasible and allows to obtain satisfactory biochemical control rates, especially in patients attaining a nPSA ≤0.35 ng/ml after EBRT.