Therapeutic applications of radioactive sources: From image-guided brachytherapyto radio-guided surgical resection

It is well known nowadays that radioactivity can destroy the living cells it interacts with. it is therefore unsurprising that radioactive sources, such as iodine-125, were historically developed for treatment purposes within radiation oncology with the goal of damaging malignant cells. however, since then, new techniques have been invented that make creative use of the same radioactivity properties of these sources for medi- cal applications. here, we review two distinct kinds of therapeutic uses of radioactive sources with applications to prostate, cervical, and breast cancer: brachytherapy and radioactive seed localization. in brachytherapy (BT), the radioactive sources are used for internal radiation treatment. current approaches make use of real-time image guidance, for instance by means of magnetic resonance imaging, ultrasound, computed tomog- raphy, and sometimes positron emission tomography, depending on clinical availability and cancer type. Such image-guided BT for prostate and cervical cancer presents a promising alternative and/or addition to external beam radiation treatments or surgical resections. radioactive sources can also be used for radio-guided tumor localization during surgery, for which the example of iodine-125 seed use in breast cancer is given. radioactive seed localization (rSl) is increasingly popular as an alternative tumor localization technique during breast cancer surgery. Advantages of applying RSL include added flexibility in the clinical scheduling logistics, an increase in tumor localization accuracy, and higher patient satisfaction; safety measures do however have to be employed. We exemply the implementation of rSl in a clinic through our experi- ences at the netherlands cancer institute

Minimally invasive complete response assessment of the breast after neoadjuvant systemic therapy for early breast cancer (micra trial) : interim analysis of a multicenter observational cohort study

Background The added value of surgery in breast cancer patients with pathological complete response (pCR) after neoadjuvant systemic therapy (NST) is uncertain. The accuracy of imaging identifying pCR for omission of surgery, however, is insufficient. We investigated the accuracy of ultrasound-guided biopsies identifying breast pCR (ypT0) after NST in patients with radiological partial (rPR) or complete response (rCR) on MRI. Methods We performed a multicenter, prospective single-arm study in three Dutch hospitals. Patients with T1-4(N0 or N +) breast cancer with MRI rPR and enhancement <= 2.0 cm or MRI rCR after NST were enrolled. Eight ultrasound-guided 14-G core biopsies were obtained in the operating room before surgery close to the marker placed centrally in the tumor area at diagnosis (no attempt was made to remove the marker), and compared with the surgical specimen of the breast. Primary outcome was the false-negative rate (FNR). Results Between April 2016 and June 2019, 202 patients fulfilled eligibility criteria. Pre-surgical biopsies were obtained in 167 patients, of whom 136 had rCR and 31 had rPR on MRI. Forty-three (26%) tumors were hormone receptor (HR)-positive/HER2-negative, 64 (38%) were HER2-positive, and 60 (36%) were triple-negative. Eighty-nine patients had pCR (53%; 95% CI 45-61) and 78 had residual disease. Biopsies were false-negative in 29 (37%; 95% CI 27-49) of 78 patients. The multivariable associated with false-negative biopsies was rCR (FNR 47%; OR 9.81, 95% CI 1.72-55.89; p = 0.01); a trend was observed for HR-negative tumors (FNR 71% in HER2-positive and 55% in triple-negative tumors; OR 4.55, 95% CI 0.95-21.73; p = 0.058) and smaller pathological lesions (6 mm vs 15 mm; OR 0.93, 95% CI 0.87-1.00; p = 0.051). Conclusion The MICRA trial showed that ultrasound-guided core biopsies are not accurate enough to identify breast pCR in patients with good response on MRI after NST. Therefore, breast surgery cannot safely be omitted relying on the results of core biopsies in these patients

Oncoplastic breast consortium recommendations for mastectomy and whole breast reconstruction in the setting of post-mastectomy radiation therapy

Aim: Demand for nipple-and skin-sparing mastectomy (NSM/SSM) with immediate breast reconstruction (BR) has increased at the same time as indications for post-mastectomy radiation therapy (PMRT) have broadened. The aim of the Oncoplastic Breast Consortium initiative was to address relevant questions arising with this clinically challenging scenario. Methods: A large global panel of oncologic, oncoplastic and reconstructive breast surgeons, patient advocates and radiation oncologists developed recommendations for clinical practice in an iterative process based on the principles of Delphi methodology. Results: The panel agreed that surgical technique for NSM/SSM should not be formally modified when PMRT is planned with preference for autologous over implant-based BR due to lower risk of long-term complications and support for immediate and delayed-immediate reconstructive approaches. Nevertheless, it was strongly believed that PMRT is not an absolute contraindication for implant-based or other types of BR, but no specific recom-mendations regarding implant positioning, use of mesh or timing were made due to absence of high-quality evidence. The panel endorsed use of patient-reported outcomes in clinical practice. It was acknowledged that the shape and size of reconstructed breasts can hinder radiotherapy planning and attention to details of PMRT techniques is important in determining aesthetic outcomes after immediate BR. Conclusions: The panel endorsed the need for prospective, ideally randomised phase III studies and for surgical and radiation oncology teams to work together for determination of optimal sequencing and techniques for PMRT for each patient in the context of BRPeer reviewe

Feasibility of Ex Vivo Margin Assessment with Hyperspectral Imaging during Breast-Conserving Surgery: From Imaging Tissue Slices to Imaging Lumpectomy Specimen

Developing algorithms for analyzing hyperspectral images as an intraoperative tool for margin assessment during breast-conserving surgery requires a dataset with reliable histopathologic labels. The feasibility of using tissue slices hyperspectral dataset with a high correlation with histopathology for developing an algorithm for analyzing the images from the surface of lumpectomy specimens was investigated. We presented a method to acquire hyperspectral images from the lumpectomy surface with a high correlation with histopathology. The tissue slices dataset was compared with the dataset obtained on lumpectomy specimen and the wavelengths with a penetration depth up to the minimum sample thickness of the tissue slices were used to develop a tissue classification algorithm. Spectral differences were observed between tissue slices and lumpectomy datasets due to differences in the sample thickness between both datasets; wavelengths with a high penetration depth were able to penetrate through the thinner tissue slices, affecting the captured signal. By using only wavelengths with a penetration depth up to the minimum sample thickness of the tissue slices, the adipose tissue could be discriminated from other tissue types, but differentiating malignant from connective tissue was more challenging

Feasibility of ex vivo margin assessment with hyperspectral imaging during breast-conserving surgery: From imaging tissue slices to imaging lumpectomy specimen

Developing algorithms for analyzing hyperspectral images as an intraoperative tool for margin assessment during breast-conserving surgery requires a dataset with reliable histopatho-logic labels. The feasibility of using tissue slices hyperspectral dataset with a high correlation with histopathology for developing an algorithm for analyzing the images from the surface of lumpec-tomy specimens was investigated. We presented a method to acquire hyperspectral images from the lumpectomy surface with a high correlation with histopathology. The tissue slices dataset was compared with the dataset obtained on lumpectomy specimen and the wavelengths with a penetration depth up to the minimum sample thickness of the tissue slices were used to develop a tissue classification algorithm. Spectral differences were observed between tissue slices and lumpectomy datasets due to differences in the sample thickness between both datasets; wavelengths with a high penetration depth were able to penetrate through the thinner tissue slices, affecting the captured signal. By using only wavelengths with a penetration depth up to the minimum sample thickness of the tissue slices, the adipose tissue could be discriminated from other tissue types, but differentiating malignant from connective tissue was more challenging

Nationwide registry study on trends in localization techniques and reoperation rates in non-palpable ductal carcinoma in situ and invasive breast cancer

BACKGROUND: There is a transition from wire-guided localization (WGL) of non-palpable breast cancer to other localization techniques. Multiple prospective studies have sought to establish superior clinical outcomes for radioactive-seed localization (RSL), but consistent and congruent evidence is missing. METHODS: In this study, female patients with breast cancer operated with breast-conserving surgery after tumour localization of a non-palpable breast cancer or ductal carcinoma in situ (DCIS) were included. The cohort was identified from the nationwide Netherlands Breast Cancer Audit conducted between 2013 and 2018. Trends in localization techniques were analysed. Univariable and multivariable analyses were performed to assess the association between the localization technique and the probability of a reoperation. RESULTS: A total of 28 370 patients were included in the study cohort. The use of RSL increased from 15.7 to 61.1 per cent during the study years, while WGL decreased from 75.4 to 31.6 per cent. The localization technique used (RSL versus WGL) was not significantly associated with the odds of a reoperation, regardless of whether the lesion was DCIS (odds ratio 0.96 (95 per cent c.i. 0.89 to 1.03; P = 0.281)) or invasive breast cancer (OR 1.02 (95 per cent c.i. 0.96 to 1.10; P = 0.518)). CONCLUSION: RSL is rapidly replacing WGL as the preoperative localization technique in breast surgery. This large nationwide registry study found no association between the type of localization technique and the odds of having a reoperation, thus confirming the results of previous prospective cohort studies

Locoregional lymph node involvement on 18F-FDG PET/CT in breast cancer patients scheduled for neoadjuvant chemotherapy

The optimal method for locoregional staging in patients treated with neoadjuvant chemotherapy (NAC), usually ultrasound (US) and pre- or post-chemotherapy sentinel lymph node biopsy (SLNB), remains subject of debate. The aim of this study was to assess the value of 18F-FDG PET/CT for detecting locoregional lymph node metastases in primary breast cancer patients scheduled for NAC. 311 breast cancer patients, scheduled for NAC, underwent PET/CT of the thorax in prone position with hanging breasts. A panel of four experienced reviewers examined PET/CT images, blinded for other diagnostic procedures. FDG uptake in locoregional nodes was determined qualitatively using a 4-point scale (0 = negative, 1 = questionable, 2 = moderately intense, and 3 = very intense). Results were compared with pathology obtained by US-guided fine needle aspiration or SLNB prior to NAC. All FDG-avid extra-axillary nodes were considered metastatic, based on the previously reported high positive predictive value of the technique. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FDG-avid nodes for the detection of axillary metastases (score 2 or 3) were 82, 92, 98, 53, and 84 %, respectively. Of 28 patients with questionable axillary FDG uptake (score 1), 23 (82 %) were node-positive. Occult lymph node metastases in the internal mammary chain and periclavicular area were detected in 26 (8 %) and 32 (10 %) patients, respectively, resulting in changed regional radiotherapy planning in 50 (16 %) patients. In breast cancer patients scheduled for NAC, PET/CT renders pre-chemotherapy SLNB unnecessary in case of an FDG-avid axillary node, enables axillary response monitoring during or after NAC, and leads to changes in radiotherapy for a substantial number of patients because of detection of occult N3-disease. Based on these results, we recommend a PET/CT as a standard staging procedure in breast cancer patients scheduled for NA

Hyperspectral imaging for resection margin assessment during cancer surgery

Purpose: Complete tumor removal during cancer surgery remains challenging due to the lack of accurate techniques for intraoperative margin assessment. This study evaluates the use of hyperspectral imaging for margin assessment by reporting its use in fresh human breast specimens. Experimental Design: Hyperspectral data were first acquired on tissue slices from 18 patients after gross sectioning of the resected breast specimen. This dataset, which contained over 22,000 spectra, was well correlated with histopathology and was used to develop a support vector machine classification algorithm and test the classification performance. In addition, we evaluated hyperspectral imaging in clinical practice by imaging the resection surface of six lumpectomy specimens. With the developed classification algorithm, we determined if hyperspectral imaging could detect malignancies in the resection surface. Results: The diagnostic performance of hyperspectral imaging on the tissue slices was high; invasive carcinoma, ductal carcinoma in situ, connective tissue, and adipose tissue were correctly classified as tumor or healthy tissue with accuracies of 93%, 84%, 70%, and 99%, respectively. These accuracies increased with the size of the area, consisting of one tissue type. The entire resection surface was imaged within 10 minutes, and data analysis was performed fast, without the need of an experienced operator. On the resection surface, hyperspectral imaging detected 19 of 20 malignancies that, according to the available histopathology information, were located within 2 mm of the resection surface. Conclusions: These findings show the potential of using hyperspectral imaging for margin assessment during breastconserving surgery to improve surgical outcome