A review of the management of ductal carcinoma in situ following breast conserving surgery

Ductal carcinoma in situ (DCIS) is a heterogeneous, pre-malignant disease accounting for 10-20% of all new breast tumours. Evidence shows a statistically significant local control benefit for adjuvant radiotherapy (RT) following breast conserving surgery (BCS) for all patients. The baseline recurrence risk of individual patients varies according to clinical-pathological criteria and in selected patients, omission of RT may be considered, following a discussion with the patient. The role of adjuvant endocrine therapy remains uncertain. Ongoing studies are attempting to define subgroups of patients who are at sufficiently low risk of recurrence that RT may be safely omitted; investigating RT techniques and dose fractionation schedules; and defining the role of endocrine therapy. Future directions in the management of patients with DCIS will include investigation of prognostic and predictive biomarkers to inform individualised therapy tailored to the risk of recurrence

Rinsh¯o-hoshasen

Introduction: Detailed, published surveys specific to Australian breast radiotherapy practice were last conducted in 2002. More recent international surveys specific to breast radiotherapy practice include a European survey conducted in 2008/2009 and a Spanish survey conducted in 2009. Radiotherapy techniques continue to evolve, and the utilisation of new techniques, such as intensity-modulated radiation therapy (IMRT), is increasing. This survey aimed to determine current breast radiotherapy practices across Australia. Method: An online survey was completed by 50 of the 69 Australian radiation therapy treatment centres. Results: Supine tangential beam whole breast irradiation remains the standard of care for breast radiotherapy in Australia. A growing number of institutions are exploring prone positioning and IMRT utilisation. This survey demonstrated a wide variation in the benchmarks used to limit and report organ at risk doses, prescribed dose regimen, and post-mastectomy bolus practices. This survey also indicated, when compared with international literature, that there may be less interest in or uptake of external beam partial breast irradiation, prone positioning, simultaneous integrated boost and breath hold techniques. These are areas where further review and research may be warranted to ensure Australian patients are receiving the best care possible based on the best evidence available. Conclusion: This survey provides insight into the current radiotherapy practice for breast cancer in Australia

Comparison of Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) for breast target volume delineation in prone and supine positions

Purpose/Objective(s): MRI provides no ionizing radiation dose (allowing inter and intra fraction imaging), improved soft tissue contrast and potentially improved conformity in delineation than CT. This study aimed to determine if T2 weighted magnetic resonance imaging improves seroma cavity (SC) and Whole Breast (WB) inter-observer conformity for radiotherapy purposes compared with the gold standard of CT, both in the prone and supine positions. Methods and Materials: Eleven observers (two Radiologists and nine Radiation Oncologists) delineated SC and WB Clinical Target Volumes (CTVs) on T2-weighted MRI and CT supine and prone scans (4 scans per patient) for 33 patient datasets. Individual observer’s volumes were compared using the Dice Similarity Coefficient (DSC), Volume overlap Index (VOI), Centre of Mass (COM) shift and Hausdorff Distances (HD). An average Cavity Visualization Score (CVS) was also determined. Results: Imaging modality did not affect inter-observer variation for WB CTVs. Prone WB CTVs were larger in volume and more conformal than Supine CTVs (on both MRI and CT). SC volumes were larger on CT than MRI. SC volumes proved to be comparable in inter-observer conformity in both modalities (VOI of 0.57±0.03 for CT supine, 0.52±0.04 for MR supine, 0.56±0.03 for CT prone and 0.55±0.04 for MR prone) however after registering modalities together the inter-modality variation (DSC of 0.41±0.05 for supine and 0.38±0.04 for prone) was larger than the inter-observer variability for SC despite the location typically remaining constant. Conclusions: MRI inter-observer variation was comparable to CT for the WB CTV and SC delineation, in both prone and supine positions. Whilst the CVS and inter-observer concordance was not significantly higher for MRI than CT, the SCs were smaller on MRI, potentially due to clearer SC definition, especially on T2-weighted MR images

Hypofractionated versus conventionally fractionated radiotherapy for ductal carcinoma in situ (DCIS) of the breast

Introduction: Hypofractionated radiotherapy (RT) in the setting of early invasive breast cancer has been shown to have similar local control rates and cosmetic outcomes as conventionally fractionated RT. This study compares ipsilateral recurrence rates between hypofractionated and conventional RT, with and without a boost. The effect of hypofractionated RT and chest wall separation (CWS) on cosmetic outcome was also assessed. Methods: All patients with ductal carcinoma in situ (DCIS) treated between 1998 and 2012 across two sites of a single cancer institution were retrospectively studied. Patients were analysed according to those receiving conventional RT (≤2 Gy per fraction) and those receiving hypofractionated RT (>2 Gy per fraction), as well as the presence or absence of a tumour bed boost. Data were collected through electronic medical records and local cancer registry. Cosmetic outcome was scored by physicians on a four-point scale during clinical follow-up appointments. Results: One hundred and ninety-seven patients were treated for DCIS during the study period. One hundred and forty-one were treated with conventional RT, and 56 with hypofractionated RT. After a median follow up of 4.4 years, there were 12 ipsilateral recurrences, of which seven were invasive disease and five DCIS. Ten recurrences occurred in patients who received conventional RT (7.1% recurrence rate) and two in those who received hypofractionated RT (3.6% recurrence rate) (P = 0.48). Cosmetic outcomes were not significantly different between conventional and hypofractionated RT (P = 0.06). Conclusions: Hypofractionation represents a suitable alternative for treating DCIS in the absence of randomised data

Predicting Response to Radioimmunotherapy from the Tumor Microenvironment of Colorectal Carcinomas

Solid tumors have a heterogeneous pathophysiology, which directly affects antibody-targeted therapies. Here, we consider the influence of selected tumor parameters on radioimmunotherapy, by comparing the gross biodistribution, microdistribution, and therapeutic efficacy of either radiolabeled or fluorescently labeled antibodies (A5B7 anti-carcinoembryonic antigen antibody and a nonspecific control) after i.v. injection in two contrasting human colorectal xenografts in MF1 nude mice. The LS174T is moderately/poorly differentiated, whereas SW1222 has a well-differentiated glandular structure. Biodistribution studies (1.8 MBq (131) I-labeled A5B7, four mice per group) showed similar gross tumor uptake at 48 It in the two models (25.1% and 24.0% injected dose per gram, respectively). However, in therapy studies (six mice per group), LS174T required a 3-fold increase in dose (18 versus 6 MBq) to equal SW1222 growth inhibition (similar to 55 versus similar to 60 days, respectively). To investigate the basis of this discrepancy, high-resolution multifluorescence microscopy was used to study antibody localization in relation to tumor parameters (5 min, I and 24 h, four mice per time point). Three-dimensional microvascular corrosion casting and transmission electron microscopy showed further structural differences between xenografts. Vascular supply, overall antigen distribution, and tumor structure varied greatly between models, and were principally responsible for major differences in antibody localization and subsequent therapeutic efficacy. The study shows that multiparameter, high-resolution imaging of both therapeutic and tumor microenvironment is required to comprehend complex antibody-tumor interactions, and to determine which tumor regions are being successfully treated. This will inform the design of optimized clinical trials of single and combined agents, and aid individual patient selection for antibody-targeted therapies