Proton Therapy in the Treatment of Men with Breast Cancer

Purpose: Male breast cancer treatment involves multimodality therapy, including radiation therapy; nevertheless, few men have received proton therapy (PT) for it. Further, heart disease is an established leading cause of death in men, and radiation therapy heart dose correlates with cardiac toxicity, highlighting the need for cardiac-sparing radiation techniques. Thus, we provide a descriptive analysis of PT in a male breast cancer cohort. Patients and Methods: Men who received PT for localized breast cancer between 2012 and 2022 were identified from a prospective database. Toxicities were prospectively recorded by using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Results: Five male patients were identified. All had estrogen receptor (ER)–positive, Her2neu-negative disease and received adjuvant endocrine therapy. One had genetic testing positive for BRCA2, one had a variant of unknown significance (VUS) in the APC gene, and one had a VUS in MSH2. Median age was 73 years (range, 41–80). Baseline comorbidities included obesity (n = 1), diabetes (n = 1), hypertension (n = 4), history of deep vein thrombosis (n = 1), personal history of myocardial infarction (n = 3; 1 with a pacemaker), and a history of lung cancer (n = 1). All received PT to the left chest wall and comprehensive regional lymphatics. One received passive-scattering PT, and 4 received pencil beam scanning. One patient received a boost to the mastectomy incision via electrons. Median heart dose was 1 GyRBE (range, 0–1.0), median 0.1-cm3 dose to the left anterior descending artery was 7.5 GyRBE (range, 0–14.2), and median follow-up was 2 years (range, 0.75–6.5); no patient experienced a new cardiac event, and all remain free from breast cancer recurrence and progression. Conclusion: In a small case series for a rare diagnosis, PT to the chest wall and regional lymphatics, including internal mammary nodes, resulted in low cardiac exposure, high local regional disease control rates, and minimal toxicity. Proton therapy should be considered for treating men with breast cancer to achieve cardiac sparing

Towards understanding and reducing late side effects of radiotherapy in breast cancer patients

The goal of this dissertation was to gain insight in the different aspects of several late side effects in breast cancer patients who had breast-saving treatment. It appears that a higher dose of radiation (a photon boost instead of an electron boost), a larger radiation area and supplementary chemotherapies are risk factors for a cosmetically less attractive breast. Additionally, we found that our Voluntary moderately Deep Inspiration Breath Hold technique (patient holds their breath during radiation) is a simple and valuable way to reduce the radiated heart volume and therefore later-occurring cardiac damage. Lastly, we demonstrated the structural registration of late side effects through patient questionnaires ensures patients who need extra care are identified. Structural registration also makes the development of prognostic models possible as well as outcome data comparison among centres

A Prospective single arm study to assess the feasibility and tolerability of hypo fractionated post mastectomy radiotherapy in patients with carcinoma breast

INTRODUCTION: Breast cancer is one disease, the management of which keeps evolving and continues to baffle the clinician from ages. The surge for refinement in treatment modalities of breast cancer is ever growing and it is one of the most extensively studied diseases. Being the commonest cancer among women in the developed world, tremendous amount of research has gone into understanding the biology of this disease and novel treatment approaches are being investigated across the world. Breast cancer is a disease with potential for systemic spread with high risk of local recurrence. Essentially, the treatment of invasive breast cancer has surgery and radiation therapy as the modes for local control of the disease and chemotherapy for addressing the systemic micrometastasis. Radiation therapy is inherent in the setting of breast conservation therapy. Modified radical mastectomy is followed up with radiation therapy to the chest wall, supraclavicular or the axillary region according to specific indications. OBJECTIVES: To study the tolerability of hypofractionated post- mastectomy radiotherapy in terms of acute toxicities, especially dermatitis. Feasibility in terms of target coverage and dose limits to organs at risk were studied. METHODS: A single arm prospective study was done on patients diagnosed to have carcinoma breast with indications for post mastectomy radiotherapy and are willing for 3D Conformal Radiotherapy. The dose delivered was 40Gy in 15 fractions to chest wall alone or chest wall and supraclavicular regions. Weekly clinically examinations were done to assess acute toxicities. DVH data were collected to study the influence of regions treated on CTV coverage, dose to organs at risk. Data entry was done in Micrsoft Excel and was analysed using SPSS 16.0. Frequencies and percentages were calculated for discrete variables. The association between the outcome variables was tested using Chi square test. RESULTS: Out of the 12 patients, only one developed Grade III dermatitis. None of the patients developed Grade IV toxicities. Patients tolerated the treatment well. It was noted that the median V10Gy (26.1 % vs 16.9 %, p value 0.003) and V12Gy (25.2 % vs 16.23 %, p value 0.003) for ipsilateral lung was significantly high when there was an addition of supraclavicular field. We conclude that hypofractionated radiotherapy is a tolerable treatment regimen. Obese, left sided breast cancer patients who require supraclavicular irradiation may benefit from IMRT. CONCLUSION: Hypofractionated post mastectomy irradiation was well tolerated by our patients in terms of acute toxicities. Patients completed treatment without any delay or treatment breaks. There were no significant toxicity upto six weeks post treatment. The rate and severity of acute side effects were comparable with conventional radiotherapy. Long term effects on the lung, heart and contralateral breast needs to be studied. Patients were very satisfied about the convenience of this shorter radiotherapy schedule. As far as feasibility was concerned, we conclude that Three Dimensional Radiotherapy based hypofractionation might not be feasible in all patients. There is a subset of patients who may benefit from IMRT. Obese patients, with left sided disease and who also require supraclavicular irradiation might benefit from IMRT. The fact that supraclavicular radiation has significantly contributed to the lung dose even in conformal radiotherapy, where in the volume is relatively small, further urges us to be cautious while planning the supraclavicular field conventionally

Phase II Clinical Trial of Concurrent Neoadjuvant Chemotherapy With Radiotherapy in Locally Advanced Breast Cancer

Locally advanced breast cancer (LABC) represents 15% of all non-metastatic breast cancers, with an overall poor prognosis, despite current guidelines that recommend neoadjuvant chemotherapy followed by surgery and adjuvant radiation. Therefore, a novel treatment paradigm using concurrent neoadjuvant chemoradiotherapy was proposed. A clinical trial was designed, where 32 LABC patients were treated with q3 weekly 5-fluorouracil, epirubicin and cyclophosphamide for three cycles, followed by weekly docetaxel for 9 weeks with concurrent regional radiation (45+5.4Gy) for the first 6 weeks. Patients subsequently underwent modified radical mastectomies. Pathological complete responses (pCR) and 3 year overall survival rates were compared to a matched concurrent control cohort. The concurrent chemoradiation cohort saw a significant increase in pCR rate and a trend toward 15% improvement in overall survival that failed to reach statistical significance. This regimen was not without toxicity, and 25% of patients experienced grade 3 or greater dermatitis and 25% experienced grade 3 or greater pneumonitis, resulting in one death. Tumour biomarker, plasma osteopontin, prior to chemotherapy was found to significantly predict for overall survival. In conclusion, LABC is an aggressive subset of breast cancer for which novel regimens must continue to be developed, taking advantage of the improved response to treatment with radiosensitivity seen in this concurrent chemoradiation regimen, but using alternative radiosensitizing agents to minimize toxicity

Level of Anxiety in Breast Cancer Patients receiving Locoregional Radiation Therapy and Its correlation with inter-fraction variations observed during delivery of treatment

INTRODUCTION : Breast cancer is the most frequent cancer among women according to the GLOBOCON 2012 report contributing to 27% of all new cancers in women in India. Radiation therapy forms an integral part of its multi-modality treatment. Various studies have found a significant level of anxiety among patients undergoing radiation therapy due to fear of unknown. During delivery of radiation therapy for breast cancer patients, other than setup uncertainties, target motion due to breathing is also significant. High anxiety levels may lead to significant change in breathing pattern which could result in larger setup variations observed during the treatment. AIMS AND OBJECTIVES : Our study aimed to estimate the level of anxiety in non metastatic breast cancer patients undergoing radiation therapy. It also aimed to measure the inter fraction variations and to determine any correlation between the observed anxiety levels and inter fraction variations recorded during the treatment. Thus, trying to determine the need of counseling for anxious patients to reduce these errors. METHODS AND MATERIALS : The anxiety levels were measured using the Beck Anxiety Inventory (BAI) questionnaire which contains 21 items. It was administered at the time of simulation, first three days of treatment and weekly once during the course of treatment. The inter-fraction variation was measured using the electronic portal images for the same days and correlation was calculated using Pearson correlation coefficient.. RESULTS: Twenty seven patients who received chest wall or whole breast irradiation with or without nodal irradiation using field in field technique were assessed. The anxiety levels were found to be high at the time of simulation and on the first day of treatment (median anxiety score was 7) , it then declined rapidly over the subsequent days(median score was 4 and 3 respectively on second and third day of treatment). The mean systemic error observed for vertical, lateral and longitudinal direction was 3.4,3.4 and 3 mm and random error for all parameters was within 5 mm. The group systematic error for central lung distance (CLD) was 3.1 mm with a standard deviation of 1.8 mm. The CLD variation compared to baseline was found to be more on the first day of treatment and was significantly correlated (r=0.45, p=0.02) with higher level of anxiety seen at starting of treatment. CONCLUSION : Patients have high anxiety levels during planning and starting of treatment. This affects the breathing pattern and therefore the treatment delivery in breast cancer patients especially on the first day of treatment. For optimal treatment and care of patients, an effort to understand the patients' anxiety and addressing it by better communication about radiation therapy procedure and likely side effects should be undertaken by the oncology team

Use of neoadjuvant chemotherapy in locally advanced breast cancer in the Netherlands

Use of neoadjuvant chemotherapy in locally advanced breast cancer in the Netherlands P.E.R. Spronk1, A.C.M. Van Bommel1, S. Siesling2,3, M.J.T. Baas- Vrancken Peeters4, C.H. Smorenburg5. 1Leiden University Medical Centre, Surgery, Leiden, Netherlands; 2Comprehensive Cancer Centre the Netherlands IKNL, Epidemiology, Utrecht, Netherlands; 3University of Twente, MIRA Biomedical science and Technical Medicine, Twente, Netherlands; 4Netherlands Cancer Institute/Antoni van Leeuwenhoek, Surgery, Amsterdam, Netherlands; 5Netherlands Cancer Institute/Antoni van Leeuwenhoek, Medical Oncology, Amsterdam, Netherlands Background: Neoadjuvant chemotherapy (NAC) is the treatment of choice for patients with locally advanced breast cancer (LABC). The aim of this study is to examine the use of NAC for LABC in all Dutch hospitals participating in breast cancer care and to assess what patient, tumour and hospital characteristics influence its use. Material and Methods: Data were derived from the national multidisciplinary NABON Breast Cancer Audit (NBCA), regarding all women aged >18 years and newly diagnosed with LABC from January 2011 to September 2013. Multivariable logistic regression was used to assess the association between the use of NAC and patient, tumour and hospital related factors. Results: Of 1419 woman diagnosed with LABC, 70% were treated with NAC. This percentage varied from 12.5% to 90% between hospitals and did not increase over time. Factors associated with the use of NAC included young age, large tumour size, more advanced nodal disease and triple negative or hormone-receptor negative tumours. Also patients treated in hospitals with a multidisciplinary preoperative work-up and participation in neoadjuvant studies were more likely to receive NAC. However, considerable variation between hospitals remained after casemix correction. Table 1. Multivariable odds ratios (ORs) for receipt of NAC among 1419 stage III patients 2011 through 2013 OR 95% CI P-value Age 0.000 5 cm 5.68 2.34−13.79 Clinical nodal status 0.000 cNx/N0 ref. cN1 1.32 0.86−2.04 cN2 2.93 1.18−7.29 cN3 10.28 4.18−25.25 Receptor status 0.000 Triple negative 2.35 1.40−3.93 HR−, Her2+ 3.37 1.67−6.78 HR+, Her2+ 0.91 0.51−1.60 HR+, Her2− ref. Type of surgery 0.026 Breast conservation therapy 2.05 1.09−3.84 Mastectomy ref. Multidisciplinary team 0.021 Yes 1.98 1.11−3.53 No ref. Type of hospital 0.569 General 1.20 0.73−1.98 Top clinical ref. Academic 1.50 0.64−3.47 Hospital surgical volume 0.729 200 1.27 0.70−2.31 Study participation 0.005 Yes 1.80 1.20−2.70 No ref. Conclusions: There is considerable variation in the use of NAC for LABC in the Netherlands. Although various patient, tumor and institutional factors are associated with the use of NAC in LABC, these can only explain part of the observed variation in treatment patterns between hospitals

IMPROVING REALTIME 3-D TRACKING OF HIGH DOSE RATE RADIATION SOURCE USING A FLAT PANEL DETECTOR

Previous research 1 on this subject tracked the presumed exact path the HDR source would follow in real-time, during breast brachytherapy treatments in other to ensure accurate dose delivery and effectively confirm actual source position. As a continuation, this research has three objectives. Firstly, we will extract information from patient DICOM file which will be used to perform evaluations, then we will establish communication between our C program and the new Varex Paxscan flat panel detector (FPD). Finally, we will try to embed our C codes into a MATLAB graphical user interface (GUI) This research will attempt to improve the overall existing system in several ways including, code optimization and trying a sample simulation of the process in MATLAB guide app, to check the quality of the new design. Finally, all the algorithms will be integrated into the user-friendly GUI, such that its operation can be implemented easily. The FPD is used to obtain images resulting from the exit radiation of the HDR source, emerging from an organized matrix of markers. The images are processed using in-built functions in MATLAB to obtain projection coordinates, and marker coordinates. Each marker along with its projection constitutes a line in 3D. Using the mathematical solution for near intersection of two 3D lines, N-markers will produce N*(N-1)/2 points of intersection and their mean will produce a more precise source position. The changes in this position as well as the time interval between these changes will be used to confirm the accuracy of our treatment system using the standalone monitoring system built in this research. In the previous study the accuracy of source position detection using the FPD was found to be in sub-millimeter. This study which uses a new FPD with improved features is used to confirm that, but our focus here is improvement of the previous work, as stated earlier