Jana Lauren Fox

Background/objective: Intra-operative radiation therapy (IORT) is a newer partial breast irradiation technique that has been well studied in 2 large randomized trials, the TARGIT-A and ELIOT trials. We initiated our IORT program in 2018 in the context of a registry trial, and aim to report our early results thus far. Methods: We instituted an IORT practice using Intrabeam® low energy 50kVp x-rays for selected breast cancer cases in 2018. Patients were enrolled on our institutional registry protocol which allowed for IORT in ER + patients with grade 1–2 DCIS ≤ 2.5 cm or invasive disease ≤ 3.5 cm in patients of at least 45 years of age. Results: Between January 2018 and December 2021, 181 patients with clinical stage 0-IIA ER + breast cancer were evaluated. One hundred sixty-seven patients ultimately received IORT to 172 sites. The majority of patients received IORT at the time of initial diagnosis and surgery (160/167; 95.8%). Re-excision post IORT occurred in 16/167 patients (9.6%) due to positive margins. Adjuvant RT to the whole breast +/- LN was ultimately given to 23/167 (13.8%) patients mainly due to positive sentinel LN found on final pathology (12/23; 52%); other reasons were close margins for DCIS (3/23; 13%), tumor size (3/23; 4.3%), and multifactorial (5/23; 17.4%). Five patients (3%) had post-operative complications of wound dehiscence. There were 3 local recurrences (1.6%) at a median follow-up of 27.9 months (range: 0.7– 54.8 months). Conclusions: IORT has been proven to be a safe and patient-centered form of local adjuvant RT for our population, in whom compliance with a longer course of external beam radiation can be an issue. Long term efficacy remains to be evaluated through continued follow up. In the era of COVID-19 and beyond, IORT has been an increasingly attractive option, as it greatly minimizes toxicities and patient visits to the clinic. Trial registration: All patients were prospectively enrolled on an institutional review board-approved registry trial (IRB number: 2018–9409).

Background/Objective: Intra-operative radiation therapy (IORT) is a newer partial breast irradiation technique that has been well studied in 2 large, randomized trials, the TARGIT-A and ELIOT trials. We initiated our IORT program in 2018 in the context of a registry trial and aim to report our early results thus far. Methods: We instituted an IORT practice using Intrabeam® low energy 50kVp x-rays for selected breast cancer cases in 2018. Patients were enrolled on our institutional registry protocol which allowed for IORT in ER+ patients with grade 1-2 DCIS ≤ 2.5cm or invasive disease ≤ 3.5cm in patients of at least 45 years of age. Results: Between January 2018 and December 2021, 181 patients with clinical stage 0-IIA ER+ breast cancer were evaluated. One hundred sixty-seven patients ultimately received IORT to 172 sites. The majority of patients received IORT at the time of initial diagnosis and surgery (160/167; 95.8%). Re-excision post IORT occurred in 16/167 patients (9.6%) due to positive margins. Adjuvant RT to the whole breast +/- LN was ultimately given to 23/167 (13.8%) patients mainly due to positive sentinel LN found on final pathology (12/23; 52%); other reasons were close margins for DCIS (3/23; 13%), tumor size (3/23; 4.3%), and multifactorial (5/23; 17.4%). Five patients (3%) had post-operative complications of wound dehiscence. There were 3 local recurrences (1.6%) at a median follow-up of 27.9 months (range: 0.7– 54.8 months). Conclusions: IORT has been proven to be a safe and patient-centered form of local adjuvant RT for our population, in whom compliance with a longer course of external beam radiation can be an issue. Long term efficacy remains to be evaluated through continued follow up. In the era of COVID-19 and beyond, IORT has been an increasingly attractive option, as it greatly minimizes toxicities and patient visits to the clinic. Trial Registration: All patients were prospectively enrolled on an institutional review board-approved registry trial (IRB number: 2018-9409).

In an era of continued advancements in personalized medicine for the treatment of breast cancer, select patients with early stage breast cancer may be uniquely poised to benefit from partial breast irradiation (PBI) delivered with proton therapy. PBI presents an opportunity to improve quality of life during treatment with a significantly shorter treatment duration. By targeting less non-target breast tissue, excess radiation exposure and resulting toxicities are also reduced. Proton therapy represents a precision radiotherapy technology that builds on these advantages by further limiting the normal tissue exposure to unnecessary radiation dose not only to uninvolved breast tissue but also the underlying thoracic organs including the heart and lungs. Herein, we present a concise review of the rationale for the use of proton therapy for PBI, evidence available to date, and practical considerations in the implementation and use of proton therapy for this indication.

The association between cancer and thrombosis has been known for over a century and a half. However, the mechanisms that underlie this correlation are not fully characterized. Hypercoagulability in cancer patients can be classified into two main categories: Type I and Type II. Type I occurs when the balance of endogenous heparin production and degradation is disturbed, with increased degradation of endogenous heparin by tumor-secreted heparanase. Type II hypercoagulability includes all the other etiologies, with factors related to the patient, the tumor, and/or the treatment. Patients with poor performance status are at higher risk of venous thromboembolism (VTE). Tumors can result in VTE through direct pressure on blood vessels, resulting in stasis. Several medications for cancer are correlated with a high risk of thrombosis. These include hormonal therapy (e.g., tamoxifen), chemotherapy (e.g., cisplatin, thalidomide and asparaginase), molecular targeted therapy (e.g., lenvatinib, osimertinib), and anti-angiogenesis monoclonal antibodies (e.g., bevacizumab and ramucirumab).

Surgical cavity sizing applicators were developed for utilization prior to intraoperative radiation therapy (IORT) of the breast lumpectomy cavity with the Zeiss INTRABEAM (Carl Zeiss Meditec AG, Jena, Germany) device. The use of these applicators minimizes the number of sterilizations of the treatment applicator, which is currently limited to 100 sterilizations per applicator. This maximizes the number of patients who can be treated with each applicator, resulting in cost savings for the treating institution.

Myoepithelial tumors of the soft tissue are a rare tumor displaying myoepithelial elements and lacking obvious ductal differentiation. The rarity of these precludes any evidence‐based consensus regarding optimal management. Nevertheless, the current approach to these lesions begins with amputation or complete excision. The efficacy of neoadjuvant or adjuvant radiation therapy or chemotherapy has not been established. Here, we present the first report to the authors’ knowledge of neoadjuvant radiation therapy for the treatment of this rare soft tissue neoplasm and review the management and outcomes of published cases of myoepithelial carcinoma. A patient with a soft tissue myoepithelial carcinoma that declined both amputation and chemotherapy was treated with neoadjuvant radiation therapy and wide surgical excision followed by a brachytherapy boost to the resected tumor bed. Neoadjuvant radiation therapy resulted in an excellent response with extensive treatment‐related changes consisting predominantly of fibrosis, hyalinization and hemorrhage and only 10% residual viable myoepithelial carcinoma present in the surgical specimen.

Objective: Fractionated stereotactic radiotherapy (FSRT) is a relatively new option for the treatment of brain metastases. We performed a quantitative systematic review to determine if local control (LC) following is affected by FSRT dosing regimen. Methods: We reviewed articles describing LC following FSRT for brain metastases. LC data from each study were extracted from actuarial survival curves and aggregated to form a single data set. LC curves were generated using the Kaplan–Meier method. Log-rank testing and Cox proportional hazards modelling were utilized to test for associations between the biologically effective dose (BED) and LC. Tumour control probability modelling was performed to illustrate the relationship between the BED and the likelihood of LC after FSRT. Results: 10 studies (720 metastases) met inclusion criteria. Prescription doses ranged from 18 to 42 Gy, delivered in 3–12 fractions (BED range: 29–100 Gy10). 1- and 2-year actuarial LC rates were 80% and 69%, respectively. Increasing BED was associated with improved LC (HR = 0.77 per increase of 10 Gy10, p = 0.009). Tumour control probability models demonstrated that the BEDs of 40, 50 and 60 Gy10 yield predicted 1-year LC rates of 73%, 78% and 84%, respectively. The BEDs of 40, 50 and 60 Gy10 yield 2-year LC rates of 62%, 69% and 81%, respectively. Conclusion: FSRT provides high rates of LC for patients with brain metastases. We found evidence for a dose–response relationship that should be explored in prospective trials. Advances in knowledge: This review identified a dose–response relationship for LC in patients treated with FSRT for brain metastases.

21 Background: Efforts have been made to identify women for whom radiotherapy (RT) after breast-conserving surgery (BCS) for ductal carcinoma in-situ (DCIS) can be omitted. These include development of the Memorial Sloan-Kettering (MSK) nomogram, the Van Nuys Prognostic Index (VNPI), and the DCIS Score. We assessed correlation of the predictive qualities of these 3 approaches to determine risk of local recurrence (LR) and need for RT. Methods: We calculated VNPI score and used the MSK nomogram to determine LR risks for 48 women on whom DCIS Scores were available since January 2012. Given that the DCIS Score does not account for HT, MSK risks were calculated with and without its use. 10-year LR risks from DCIS Score reports were compared with MSK nomogram estimates using the Pearson correlation coefficient. These comparisons were done for MSK LR risks with and without HT. VNPI scores yield low, intermediate and high risk categories. To compare the 3 predictive models, each patient was assigned an RT recommendation per instrument. Two 10-year LR risk “thresholds” to recommend RT were used - 10 and 15% - to account for M.D. preference. Results: For LR risk, the MSK nomogram (excluding HT) and the DCIS Score showed weak positive correlation (R = 0.346, p < 0.02), weaker when including HT (R = 0.179, p: 0.224). VNPI Score could not be calculated on 5 patients and they were excluded in comparisons involving VNPI. DCIS Score, using 15% LR risk as the RT recommendation threshold, and VNPI RT recommendations correlated in 72.1% of cases. Lowering the threshold to10% reduced the correlation to 32.6%. Comparison of the 3 approaches’ RT recommendations with a 15% threshold showed agreement in 65.1% (28/43) of cases, and a 10% threshold reduced the agreement to 18.6% (8/43). Conclusions: Our analysis shows some correlation between the MSK nomogram and the DCIS Score, more when HT is excluded. Lowering the threshold 10-year LR risk to recommend RT from 15 to 10% reduced agreement among the 3 instruments.

35 Background: The Oncotype Dx Recurrence Score for DCIS (DCIS Score) is a 12-gene assay derived from the original Oncotype DX test. The DCIS Score provides a local recurrence risk estimate at 10 years after lumpectomy for DCIS. Results can guide decisions regarding adjuvant radiation (RT). Foregoing RT can be a source of significant healthcare savings. We investigated the actual healthcare dollar savings to-date in our patients. Methods: We evaluated patients in whom the DCIS Score was ordered (x) and calculated total cost of testing. Potential cost of RT was that of IMRT as reimbursed by Medicare for a 16 fraction course, multiplied by x. Many of our patients with large breasts require IMRT for dose homogeneity and normal tissue parameters. We also calculated potential cost with 3D conformal (3D-CRT). Total potential cost was the sum of testing and treatment costs, determined for each modality. The number of patients ultimately treated (y) was also multiplied by these costs. Total actual cost was the sum of test expenses and actual treatment costs. Savings was the difference between total actual and total potential cost. Results: From 2/2012 to 5/ 2014 the DCIS Score was performed in 38 patients (x = 38). Median age was 66 (40 to 85). Grade was low in 39%, intermediate in 45%, and high in 16%. Fifty percent had necrosis and median size was 0.5 cm (0.1 to 3.1cm). The total cost of testing was $4125 * 38 = $156,750. IMRT reimburses at $23, 000 and 3D-CRT at $11,000. Potential total cost of RT ranged from $418,000 to $874, 000; testing brought total potential costs to $574, 750 to $1,030, 750. Upon receipt of test results, 12 (y) patients ultimately underwent therapy. IMRT was given in 11 patients and 3D-CRT in 1, for a total treatment cost of $264, 000. Therefore, total actual expenditures were $420, 750. Savings amounted to (574, 750 – 420, 750) = $154, 000 to (1,030, 750 – 420, 750) = $610, 000. Conclusions: In the era of rising healthcare costs, it is imperative to examine instances of possible overtreatment. The DCIS Score has the potential to save not only healthcare dollars, but to spare patients radiation side effects, time lost from work, and transportation expenses. While there are costs associated with the assay, if ordered judiciously, these can be offset by the subsequent savings from eliminating treatment.