RESUMEN

AIMS: Skin toxicity is a common adverse effect of breast radiotherapy. We investigated whether inverse-planned intensity-modulated radiotherapy (IMRT) would reduce the incidence of skin toxicity compared with forward field-in-field breast IMRT (FiF-IMRT) in early stage breast cancer. MATERIALS AND METHODS: This phase III randomised controlled trial compared whole-breast irradiation with either FiF-IMRT or helical tomotherapy IMRT (HT-IMRT), with skin toxicity as the primary end point. Patients received 50 Gy in 25 fractions and were assessed to compare skin toxicity between treatment arms. RESULTS: In total, 177 patients were available for assessment and the median follow-up was 73.1 months. Inverse IMRT achieved more homogeneous coverage than FiF-IMRT; erythema and moist desquamation were higher with FiF-IMRT compared with HT-IMRT (61% versus 34%; P < 0.001; 33% versus 11%; P < 0.001, respectively). Multivariate analysis showed large breast volume, FiF-IMRT and chemotherapy were independent factors associated with worse acute toxicity. There was no difference between treatment arms in the incidence of late toxicities. The 5-year recurrence-free survival was 96.3% for both FiF-IMRT and HT-IMRT and the 5-year overall survival was 96.3% for FiF-IMRT and 97.4% for HT-IMRT. CONCLUSIONS: Our study showed significant reduction in acute skin toxicity using HT-IMRT compared with FiF-IMRT, without significant reduction in late skin toxicities. On the basis of these findings, inverse-planned IMRT could be used in routine practice for whole-breast irradiation with careful plan optimisation to achieve the required dose constraints for organs at risk.

Asunto(s)

RESUMEN

BACKGROUND: The management of small-cell lung cancer (sclc) with radiotherapy (rt) varies, with many treatment regimens having been described in the literature. We created a survey to assess patterns of practice and clinical decision-making in the management of sclc by Canadian radiation oncologists (ros). METHODS: A 35-item survey was sent by e-mail to Canadian ros. The questions investigated the role of rt, the dose and timing of rt, target delineation, and use of prophylactic cranial irradiation (pci) in limited-stage (ls) and extensive-stage (es) sclc. RESULTS: Responses were received from 52 eligible ros. For ls-sclc, staging (98%) and simulation or dosimetric (96%) computed tomography imaging were key determinants of rt suitability. The most common dose and fractionation schedule was 40-45 Gy in 15 once-daily fractions (40%), with elective nodal irradiation performed by 31% of ros. Preferred management of clinical T1/2aN0 sclc favoured primary chemoradiotherapy (64%). For es-sclc, consolidative thoracic rt was frequently offered (88%), with a preferred dose and fractionation schedule of 30 Gy in 10 once-daily fractions (70%). Extrathoracic consolidative rt would not be offered by 23 ros (44%). Prophylactic cranial irradiation was generally offered in ls-sclc (100%) and es-sclc (98%) after response to initial treatment. Performance status, baseline cognition, and pre-pci brain imaging were important patient factors assessed before an offer of pci. CONCLUSIONS: Canadian ros show practice variation in sclc management. Future clinical trials and national treatment guidelines might reduce variability in the treatment of early-stage disease, optimization of dose and targeting in ls-sclc, and definition of suitability for pci or consolidative rt.

RESUMEN

AIMS: The Canadian Association of Radiation Oncology-Stereotactic Body Radiotherapy (CARO-SBRT) Task Force was established in 2010. The aim was to define the scope of practice guidelines for the profession to ensure safe practice specific for the most common sites of lung, liver and spine SBRT. MATERIALS AND METHODS: A group of Canadian SBRT experts were charged by our national radiation oncology organisation (CARO) to define the basic principles and technologies for SBRT practice, to propose the minimum technological requirements for safe practice with a focus on simulation and image guidance and to outline procedural considerations for radiation oncology departments to consider when establishing an SBRT programme. RESULTS: We recognised that SBRT should be considered as a specific programme within a radiation department, and we provide a definition of SBRT according to a Canadian consensus. We outlined the basic requirements for safe simulation as they pertain to spine, lung and liver tumours, and the fundamentals of image guidance. The roles of the radiation oncologist, medical physicist and dosimetrist have been detailed such that we strongly recommend the development of SBRT-specific teams. Quality assurance is a key programmatic aspect for safe SBRT practice, and we outline the basic principles of appropriate quality assurance specific to SBRT. CONCLUSION: This CARO scope of practice guideline for SBRT is specific to liver, lung and spine tumours. The task force recommendations are designed to assist departments in establishing safe and robust SBRT programmes.

Asunto(s)

RESUMEN

PURPOSE: To quantitatively evaluate a lung tumour autocontouring algorithm using in-vivo lung cancer patient MR images with varying contrast to noise ratios (CNR) simulating images acquired at various MR field strengths. METHODS: A non small cell lung cancer patient with posterior lung tumour is imaged (sagittal plane) in a 3T MRI using a dynamic bSSFP sequence (FOV: 40×40cm2 , voxel size: 3.1×3.1×20mm3 , TE = 1.1ms. TR = 2.2ms, 275ms per image) under free breathing for approximately 3 minutes (650 images). Gaussian random noise is added to the 3T images to approximately simulate the equivalent CNR in images acquired at 1.5T, 1.0T, 0.5T, 0.3T and 0.2T. The moving tumour in all 3T images is contoured by a physician for reference. The first 20 of these manual contours are used for the parameters optimization of auto-contouring algorithm. The automatic contours from the remaining images are quantitatively compared with the physician's contours using the centroid's displacement and the Dice's coefficient (DC). RESULTS: The oncologist's contours of the 3T images show a maximum S-I motion of 26mm. Compared to the oncologist's contours, automatic contours have an average centroid displacement of 1.37mm, and an average DC of 0.881. The autocontouring algorithm's performance with images in the range of 1.5T to 0.5T equivalent CNRs is similar to that of the 3T data. However, for the lowest CNR datasets (0.2, 0.3T) an increase in centroid displacement and decrease in DC is observed, with mean displacements of 1.56mm, 1.71mm and DCs of 0.870, 0.836 for the 0.3T and 0.2T dataset, respectivelyConclusions: With in-vivo MR images, the autocontouring algorithm generated lung tumour contours similar to ones drawn by a physician (DC 〉 0.83). In this patient, additional CNR from 〉0.5T MRIs does not provide statistically significant improvement in the accuracy of our autocontouring software. E.Yip is supported by the Canadian Institutes of Health Research as well as Alberta Innovates - Health Solutions.

RESUMEN

The fate of breast cancer patients is dependent upon elimination or control of metastases. We studied the effect of antibody-targeted liposomes containing entrapped doxorubicin (DXR) on development of tumours in two models of breast cancer, pseudometastatic and metastatic, in mice. The former used the mouse mammary carcinoma cell line GZHI, which expresses the human MUC-1 gene (L. Ding, E.N. Lalani, M. Reddish, R. Koganty, T. Wong, J. Samuel, M.B. Yacyshyn, A. Meikle, P.Y.S. Fung, J. Taylor-Papadimitriou, B.M. Longenecker, Cancer Immunol. Immunother. 36 (1993) 9--17). GZHI cells seed into the lungs of Balb/c mice following intravenous injection. The latter used the 4T1-MUC1 cell line, a MUC-1 transfectant of the mouse mammary carcinoma cell line 4T1, which metastasizes from a primary mammary fatpad (mfp) implant to the lungs (C.J. Aslakson, F.R. Miller, Cancer Res. 52 (1992) 1399--1405). B27.29, a monoclonal antibody against the MUC-1 antigen, was used to target sterically stabilized immunoliposomes (SIL[B27.29]) to tumour cells. In vitro, SIL[B27.29] showed high specific binding to both GZHI and 4T1-MUC1 cells. The IC(50) of DXR-loaded SIL[B27.29] was similar to that of free drug for GZHI cells. In the pseudometastatic model, mice treated with a single injection of 6 mg DXR/kg in DXR-SIL[B27.29] at 24 h after cell implantation had longer survival times than those injected with non-targeted liposomal drug. In the metastatic model, severe combined immune deficiency mice given weekly injectionsx3 of 2.5 mg DXR/kg encapsulated in either targeted or non-targeted liposomes were almost equally effective in slowing growth of the primary tumour and reducing development of lung tumours. Surgical removal of the primary tumour from mfp, followed by various chemotherapy regimens, was attempted, but removal of the primary tumour was generally incomplete; tumour regrowth occurred and metastases developed in the lungs in all treatment groups. DXR-SL reduced the occurrence of regrowth of the primary tumour, whereas neither targeted liposomal drug or free drug prevented regrowth. We conclude that monoclonal antibody-targeted liposomal DXR is effective in treating early lesions in both the pseudometastatic and metastatic models, but limitations to the access of the targeted liposomes to tumour cells in the primary tumour compromised their therapeutic efficacy in treating the more advanced lesions.

Asunto(s)