Intraoperative radiotherapy in the treatment of breast cancer: a review of the evidence

The surgical treatment of early breast cancer has evolved from the removal of the entire breast and surrounding tissues (mastectomy) to the removal of the tumour together with a margin of healthy tissue (lumpectomy). Adjuvant radiotherapy, however, is still mainly given to the whole breast. Furthermore, external beam radiotherapy is often given several months after initial surgery and requires the patient to attend the radiotherapy centre daily for several weeks. A single fraction of radiotherapy given during surgery directly to the tumour bed (intraoperative radiotherapy) avoids these problems. The rationale and level-1 evidence for the safety and efficacy of the technique are reviewed

Photodynamic therapy: Inception to application in breast cancer.

Photodynamic therapy (PDT) is already being used in the treatment of many cancers. This review examines its components and the new developments in our understanding of its immunological effects as well as pre-clinical and clinical studies, which have investigated its potential use in the treatment of breast cancer

Sentinel node detection in early breast cancer with intraoperative portable gamma camera: UK experience.

PURPOSE: Access to nuclear medicine department for sentinel node imaging remains an issue in number of hospitals in the UK and many parts of the world. Sentinella(®) is a portable imaging camera used intra-operatively to produce real time visual localisation of sentinel lymph nodes. METHODS: Sentinella(®) was tested in a controlled laboratory environment at our centre and we report our experience on the first use of this technology from UK. Moreover, preoperative scintigrams of the axilla were obtained in 144 patients undergoing sentinel node biopsy using conventional gamma camera. Sentinella(®) scans were done intra-operatively to correlate with the pre-operative scintigram and to determine presence of any residual hot node after the axilla was deemed to be clear based on the silence of the hand held gamma probe. RESULTS: Sentinella(®) detected significantly more nodes compared with CGC (p < 0.0001). Sentinella(®) picked up extra nodes in 5/144 cases after the axilla was found silent using hand held gamma probe. In 2/144 cases, extra nodes detected by Sentinella(®) confirmed presence of tumour cells that led to a complete axillary clearance. CONCLUSIONS: Sentinella(®) is a reliable technique for intra-operative localisation of radioactive nodes. It provides increased nodal visualisation rates compared to static scintigram imaging and proves to be an important tool for harvesting all hot sentinel nodes. This portable gamma camera can definitely replace the use of conventional lymphoscintigrams saving time and money both for patients and the health system

Photodynamic Therapy in Primary Breast Cancer

Photodynamic therapy (PDT) is a technique for producing localized necrosis with light after prior administration of a photosensitizing agent. This study investigates the nature, safety, and efficacy of PDT for image-guided treatment of primary breast cancer. We performed a phase I/IIa dose escalation study in 12 female patients with a new diagnosis of invasive ductal breast cancer and scheduled to undergo mastectomy as a first treatment. The photosensitizer verteporfin (0.4 mg/kg) was administered intravenously followed by exposure to escalating light doses (20, 30, 40, 50 J; 3 patients per dose) delivered via a laser fiber positioned interstitially under ultrasound guidance. MRI (magnetic resonance imaging) scans were performed prior to and 4 days after PDT. Histological examination of the excised tissue was performed. PDT was well tolerated, with no adverse events. PDT effects were detected by MRI in 7 patients and histology in 8 patients, increasing in extent with the delivered light dose, with good correlation between the 2 modalities. Histologically, there were distinctive features of PDT necrosis, in contrast to spontaneous necrosis. Apoptosis was detected in adjacent normal tissue. Median follow-up of 50 months revealed no adverse effects and outcomes no worse than a comparable control population. This study confirms a potential role for PDT in the management of early breast cancer

Aesthetic outcome after breast conserving surgery and either intraoperative radiotherapy or whole breast external beam radiotherapy for early breast cancer: Objective assessment of patients in a randomized controlled trial in Lublin, Poland

The international randomized controlled TARGIT A (TARGeted Intraoperative radiotherapy) trial demonstrated non-inferiority between the technique of TARGIT (Intra-Operative RadioTherapy (IORT) with Intrabeam®) and whole-breast external beam radiotherapy (EBRT) as part of the treatment for women with early breast cancer. The aim of this sub-study was to see if the single high dose of IORT leads to impaired aesthetic outcome in a group of patients participating in the trial at a single site. Frontal digital photographs were taken of women and analyzed, blinded to treatment received, by BCCT.core software. This produced scores for various measures of color. 29 women (16 EBRT, 13 IORT) between 49 to 79 years old had photographs taken at baseline (up to 2 days prior to surgery), and again at 12 months (median 364 days). At 12 months there was a significant difference in cEMDL (p=0.002, Wilcoxon Two-Sample test, 2-sided) and other measures, indicating more “redness” in the breasts of the women in the EBRT group compared with the IORT group. This difference persisted after adjusting for tumor size, body mass index and age (p=0.0198, multiple regression analysis). This study provides further evidence for the early beneficial effect of TARGIT on aesthetic outcome

Elastic scattering spectroscopy for early detection of breast cancer: partially supervised Bayesian image classification of scanned sentinel lymph nodes

Sentinel lymph node biopsy is a standard diagnosis procedure to determine whether breast cancer has spread to the lymph glands in the armpit (the axillary nodes). The metastatic status of the sentinel node (the first node in the axillary chain that drains the affected breast) is the determining factor in surgery between conservative lumpectomy and more radical mastectomy including axillary node excision. The traditional assessment of the node requires sample preparation and pathologist interpretation. An automated elastic scattering spectroscopy (ESS) scanning device was constructed to take measurements from the entire cut surface of the excised sentinel node and to produce ESS images for cancer diagnosis. Here, we report on a partially supervised image classification scheme employing a Bayesian multivariate, finite mixture model with a Markov random field (MRF) spatial prior. A reduced dimensional space was applied to represent the scanning data of the node by a statistical image, in which normal, metastatic, and nonnodal-tissue pixels are identified. Our results show that our model enables rapid imaging of lymph nodes. It can be used to recognize nonnodal areas automatically at the same time as diagnosing sentinel node metastases with sensitivity and specificity of 85% and 94%, respectively. ESS images can help surgeons by providing a reliable and rapid intraoperative determination of sentinel nodal metastases in breast cancer

Elastic scattering spectroscopy for early detection of breast cancer: partially supervised Bayesian image classification of scanned sentinel lymph nodes

Sentinel lymph node biopsy is a standard diagnosis procedure to determine whether breast cancer has spread to the lymph glands in the armpit (the axillary nodes). The metastatic status of the sentinel node (the first node in the axillary chain that drains the affected breast) is the determining factor in surgery between conservative lumpectomy and more radical mastectomy including axillary node excision. The traditional assessment of the node requires sample preparation and pathologist interpretation. An automated elastic scattering spectroscopy (ESS) scanning device was constructed to take measurements from the entire cut surface of the excised sentinel node and to produce ESS images for cancer diagnosis. Here, we report on a partially supervised image classification scheme employing a Bayesian multivariate, finite mixture model with a Markov random field (MRF) spatial prior. A reduced dimensional space was applied to represent the scanning data of the node by a statistical image, in which normal, metastatic, and nonnodal-tissue pixels are identified. Our results show that our model enables rapid imaging of lymph nodes. It can be used to recognize nonnodal areas automatically at the same time as diagnosing sentinel node metastases with sensitivity and specificity of 85% and 94%, respectively. ESS images can help surgeons by providing a reliable and rapid intraoperative determination of sentinel nodal metastases in breast cancer

Modelling the Costs and Effects of Selective and Universal Hospital Admission Screening for Methicillin-Resistant Staphylococcus aureus

Background: Screening at hospital admission for carriage of methicillin-resistant Staphylococcus aureus (MRSA) has been proposed as a strategy to reduce nosocomial infections. The objective of this study was to determine the long-term costs and health benefits of selective and universal screening for MRSA at hospital admission, using both PCR-based and chromogenic media-based tests in various settings. Methodology/Principal Findings: A simulation model of MRSA transmission was used to determine costs and effects over 15 years from a US healthcare perspective. We compared admission screening together with isolation of identified carriers against a baseline policy without screening or isolation. Strategies included selective screening of high risk patients or universal admission screening, with PCR-based or chromogenic media-based tests, in medium (5%) or high nosocomial prevalence (15%) settings. The costs of screening and isolation per averted MRSA infection were lowest using selective chromogenic-based screening in high and medium prevalence settings, at $4,100 and$10,300, respectively. Replacing the chromogenic-based test with a PCR-based test costs $13,000 and$36,200 per additional infection averted, and subsequent extension to universal screening with PCR would cost $131,000 and$232,700 per additional infection averted, in high and medium prevalence settings respectively. Assuming $17,645 benefit per infection averted, the most cost-saving strategies in high and medium prevalence settings were selective screening with PCR and selective screening with chromogenic, respectively. Conclusions/ Significance: Admission screening costs$4,100-$21,200 per infection averted, depending on strategy and setting. Including financial benefits from averted infections, screening could well be cost saving

Molecular Subtype Classification Is a Determinant of Non-Sentinel Lymph Node Metastasis in Breast Cancer Patients with Positive Sentinel Lymph Nodes

Background: Previous studies suggested that the molecular subtypes were strongly associated with sentinel lymph node (SLN) status. The purpose of this study was to determine whether molecular subtype classification was associated with nonsentinel lymph nodes (NSLN) metastasis in patients with a positive SLN. Methodology and Principal Findings: Between January 2001 and March 2011, a total of 130 patients with a positive SLN were recruited. All these patients underwent a complete axillary lymph node dissection. The univariate and multivariate analyses of NSLN metastasis were performed. In univariate and multivariate analyses, large tumor size, macrometastasis and high tumor grade were all significant risk factors of NSLN metastasis in patients with a positive SLN. In univariate analysis, luminal B subgroup showed higher rate of NSLN metastasis than other subgroup (P = 0.027). When other variables were adjusted in multivariate analysis, the molecular subtype classification was a determinant of NSLN metastasis. Relative to triple negative subgroup, both luminal A (P = 0.047) and luminal B (P = 0.010) subgroups showed a higher risk of NSLN metastasis. Otherwise, HER2 over-expression subgroup did not have a higher risk than triple negative subgroup (P = 0.183). The area under the curve (AUC) value was 0.8095 for the Cambridge model. When molecular subtype classification was added to the Cambridge model, the AUC value was 0.8475. Conclusions: Except for other factors, molecular subtype classification was a determinant of NSLN metastasis in patient