A Voxel-Based Approach to Explore Local Dose Differences Associated With Radiation-Induced Lung Damage.

PURPOSE: To apply a voxel-based (VB) approach aimed at exploring local dose differences associated with late radiation-induced lung damage (RILD). METHODS AND MATERIALS: An interinstitutional database of 98 patients who were Hodgkin lymphoma (HL) survivors treated with postchemotherapy supradiaphragmatic radiation therapy was analyzed in the study. Eighteen patients experienced late RILD, classified according to the Radiation Therapy Oncology Group scoring system. Each patient's computed tomographic (CT) scan was normalized to a single reference case anatomy (common coordinate system, CCS) through a log-diffeomorphic approach. The obtained deformation fields were used to map the dose of each patient into the CCS. The coregistration robustness and the dose mapping accuracy were evaluated by geometric and dose scores. Two different statistical mapping schemes for nonparametric multiple permutation inference on dose maps were applied, and the corresponding P<.05 significance lung subregions were generated. A receiver operating characteristic (ROC)-based test was performed on the mean dose extracted from each subregion. RESULTS: The coregistration process resulted in a geometrically robust and accurate dose warping. A significantly higher dose was consistently delivered to RILD patients in voxel clusters near the peripheral medial-basal portion of the lungs. The area under the ROC curves (AUC) from the mean dose of the voxel clusters was higher than the corresponding AUC derived from the total lung mean dose. CONCLUSIONS: We implemented a framework including a robust registration process and a VB approach accounting for the multiple comparison problem in dose-response modeling, and applied it to a cohort of HL survivors to explore a local dose-RILD relationship in the lungs. Patients with RILD received a significantly greater dose in parenchymal regions where low doses (∼6 Gy) were delivered. Interestingly, the relation between differences in the high-dose range and RILD seems to lack a clear spatial signature.

Modeling the risk of radiation-induced lung fibrosis: Irradiated heart tissue is as important as irradiated lung.

PURPOSE: We used normal tissue complication probability (NTCP) modeling to explore the impact of heart irradiation on radiation-induced lung fibrosis (RILF). MATERIALS AND METHODS: We retrospectively reviewed for RILF 148 consecutive Hodgkin lymphoma (HL) patients treated with sequential chemo-radiotherapy (CHT-RT). Left, right, total lung and heart dose-volume and dose-mass parameters along with clinical, disease and treatment-related characteristics were analyzed. NTCP modeling by multivariate logistic regression analysis using bootstrapping was performed. Models were evaluated by Spearman Rs coefficient and ROC area. RESULTS: At a median time of 13months, 18 out of 115 analyzable patients (15.6%) developed RILF after treatment. A three-variable predictive model resulted to be optimal for RILF. The two models most frequently selected by bootstrap included increasing age and mass of heart receiving >30Gy as common predictors, in combination with left lung V5 (Rs=0.35, AUC=0.78), or alternatively, the lungs near maximum dose D2% (Rs=0.38, AUC=0.80). CONCLUSION: CHT-RT may cause lung injury in a small, but significant fraction of HL patients. Our results suggest that aging along with both heart and lung irradiation plays a fundamental role in the risk of developing RILF.

Twenty years of radiobiology in clinical practice: the Italian contribution.

AIMS AND BACKGROUND: To present the Italian state-of-the-art contribution to radiobiology of external beam radiotherapy, brachytherapy, and radionuclide radiotherapy. METHODS AND STUDY DESIGN: A survey of the literature was carried out, using PubMed, by some independent researchers of the Italian group of radiobiology. Each paper was reviewed by researchers of centers not comprising its authors. The survey was limited to papers in English published over the last 20 years, written by Italian investigators or in Italian institutions, excluding review articles. RESULTS: A total of 135 papers have been published in journals with an impact factor, with an increase in the number of published papers over time, for external beam radiotherapy rather than radionuclide radiotherapy. The quantity and quality of the papers researched constitutes a proof of the enduring interest in clinical radiobiology among Italian investigators. CONCLUSIONS: The survey could be useful to individuate expert partners for an Italian network on clinical radiobiology, addressing future collaborative investigations.

Hodgkin's lymphoma emerging radiation treatment techniques: trade-offs between late radio-induced toxicities and secondary malignant neoplasms.

BACKGROUND: Purpose of this study is to explore the trade-offs between radio-induced toxicities and second malignant neoplasm (SMN) induction risk of different emerging radiotherapy techniques for Hodgkin's lymphoma (HL) through a comprehensive dosimetric analysis on a representative clinical model. METHODS: Three different planning target volume (PTVi) scenarios of a female patient with supradiaphragmatic HL were used as models for the purpose of this study. Five treatment radiation techniques were simulated: an anterior-posterior parallel-opposed (AP-PA), a forward intensity modulated (FIMRT), an inverse intensity modulated (IMRT), a Tomotherapy (TOMO), a proton (PRO) technique. A radiation dose of 30 Gy or CGE was prescribed. Dose-volume histograms of PTVs and organs-at-risk (OARs) were calculated and related to available dose-volume constraints. SMN risk for breasts, thyroid, and lungs was estimated through the Organ Equivalent Dose model considering cell repopulation and inhomogeneous organ doses. RESULTS: With similar level of PTVi coverage, IMRT, TOMO and PRO plans generally reduced the OARs' dose and accordingly the related radio-induced toxicities. However, only TOMO and PRO plans were compliant with all constraints in all scenarios. For the IMRT and TOMO plans an increased risk of development of breast, and lung SMN compared with AP-PA and FIMRT techniques was estimated. Only PRO plans seemed to reduce the risk of predicted SMN compared with AP-PA technique. CONCLUSIONS: Our model-based study supports the use of advanced RT techniques to successfully spare OARs and to reduce the risk of radio-induced toxicities in HL patients. However, the estimated increase of SMNs' risk inherent to TOMO and IMRT techniques should be carefully considered in the evaluation of a risk-adapted therapeutic strategy.

Moderately Escalated Hypofractionated (Chemo) Radiotherapy Delivered with Helical Intensity-Modulated Technique in Stage III Unresectable Non-Small Cell Lung Cancer.

PURPOSE: To assess clinical outcomes and toxicities in patients with stage III unresectable non-small cell lung cancer (NSCLC) treated with a moderately escalated hypofractionated radiotherapy delivered with Helical Intensity-Modulated Technique in combination with sequential or concurrent chemotherapy. MATERIALS AND METHODS: Sixty-one consecutive patients considered non-progressive after two cycles of induction chemotherapy were treated with a moderately escalated hypofractionated radiation course of 30 daily fractions of 2.25-2.28 Gy each administered in 6 weeks up to a total dose of 67.5-68.4 Gy (range, 64.5-71.3 Gy). Thirty-two received sequential RT after two more cycles (total = 4 cycles) of chemotherapy, while 29 were treated with concurrent chemo-radiation. The target was considered the gross tumor volume and the clinically proven nodal regions, without elective nodal irradiation. RESULTS: With a median follow up of 27 months (range 6-40), 1-year and 2-year OS rate for all patients was 77 and 53%, respectively, with a median survival duration of 18.6 months in the sequential group and 24.1 months in the concomitant group. No Grade ≥4 acute and late toxicity was reported. Acute Grade 3 treatment-related pneumonitis was detected in 10% of patients. Two patients, both receiving the concurrent schedule, developed a Grade 3 acute esophagitis. The overall incidence of late Grade 3 lung toxicity was 5%. No patients experienced a Grade 3 late esophageal toxicity. CONCLUSION: A moderately hypofractionated radiation course delivered with a Helical Intensity-Modulated Technique is a feasible treatment option for patients with unresectable locally advanced NSCLC receiving chemotherapy (sequentially or concurrently). Hypofractionated radiotherapy with a dedicated technique allows safely dose escalation, minimizing the effect of tumor repopulation that may occur with prolonged treatment time.

Radiotherapy for inoperable non-small cell lung cancer using helical tomotherapy.

AIM: To investigate the impact of tomotherapy on the dose delivered to the lungs and other normal tissues. MATERIAL AND METHODS: From February 2008 to May 2009, 35 patients with stage IIIA/IIIB non-small cell lung cancer were treated with helical tomotherapy at the S. Camillo-Forlanini Hospital. For our study we selected 20 patients who underwent chemotherapy followed by sequential radiotherapy. The planning target volume was delineated using planning CT scan and FDG-PET. The mean prescribed radiation dose was 67.5 Gy delivered in 30 fractions at a dose of 2.25 Gy per fraction. RESULTS: Median follow-up was 12.3 months. All patients developed acute esophageal toxicity, 15 of RTOG grade 1 and 5 of RTOG grade 2. At first follow-up 15 patients presented stable disease or partial response, 4 patients presented complete response, and 1 patient presented disease progression. CONCLUSIONS: Helical tomotherapy is useful to achieve dose-per-fraction escalation without increasing the treatment-related morbidity. Our results applying dose escalation were encouraging considering that we delivered doses that may be difficult to achieve with 3-dimensional treatments with no excessive complication rates.

Evaluation of helical tomotherapy in the treatment of high-grade gliomas near critical structures.

BACKGROUND: Our purpose was to investigate the role of helical tomotherapy using a simultaneous integrated boost technique for the treatment of high-grade gliomas near intracranial critical structures. METHODS AND MATERIALS: Of 27 patients treated with helical tomotherapy, 11 were eligible. Only patients whose tumors were within 0.5 cm of the optic chiasm, the optic nerve or the brainstem were included. The therapeutic approach was a simultaneous integrated boost, prescribing 66 and 60 Gy to the PTV1 and PTV2, respectively, in 30 fractions. All patients received concomitant temozolomide at a dose of 75 mg/m2 daily during radiation therapy. RESULTS: Of the 11 patients considered, 3 patients (27%) died after 4 months from the completion of the combined treatment. Three patients (27%) presented local progression, and the median time to disease progression was 6 months (range, 1-12). Five patients (45%), at the time of this evaluation, did not have signs or symptoms of recurrence or progression of the disease. Acute toxicity, evaluated during radiochemotherapy, was minimal, with all patients experiencing RTOG grade 0 and grade 1 toxicity. CONCLUSIONS: . Helical tomotherapy proved to be an effective and safe treatment modality, with an improvement of accuracy in delivery of high-dose radiotherapy despite the presence of nearby critical structures.