Implementation of an HDR brachytherapy–based breast IORT program: Initial experiences

PurposeA multidisciplinary team at our institution developed a novel method of intraoperative breast radiation therapy (precision breast intraoperative radiation therapy [PB-IORT]) that uses high-dose-rate brachytherapy with CT on-rails imaging to deliver high-dose, customized radiotherapy to patients with early-stage breast cancer. This report summarizes our program's experience developing and implementing PB-IORT.Methods and MaterialsLiterature on PB-IORT was reviewed including published articles and abstracts. To evaluate case volume, all patients with a breast cancer diagnosis who underwent breast surgery or breast radiation (2010–2017) at our academic institution were identified. Patients were stratified into pre-IORT and post-IORT eras with initiation of our PB-IORT program in October 2013. Overall trends in surgical and radiation therapy volume in each era were analyzed by linear regression. Travel distance for all surgical patients was calculated using Google Maps (Alphabet Inc.) and then compared between IORT and non-IORT patients.ResultsData from a PB-IORT Phase 1 trial found that the primary endpoints were met and that PB-IORT is feasible and safe. The direct health system's delivery costs for PB-IORT exceed those of 16-fraction whole-breast irradiation when accounting for consumable supplies (multilumen balloon applicator = $2,750 per patient). There was a significant increase in yearly growth of breast cancer surgical volume with PB-IORT.ConclusionsAccrual rates for the ongoing Phase II trial have been quicker than expected in an area where more research is needed. The rapid accrual indicates patient interest and demand for this treatment and that it is very feasible to get more data from randomized trials.     

Margin index: a useful tool for the breast surgeon?

Background

In breast conservation surgery (BCS) for breast cancer, the appropriate surgical margin is controversial. Margin index, a mathematical relationship between tumor size and closest margin, has been shown to be predictive of the probability of residual cancer after BCS for early stage breast cancer. We applied this tool to the same population of patients at our institution to evaluate its ability to predict residual disease after BCS.

Methods

We retrospectively reviewed a prospectively maintained database of women undergoing BCS between 1980 and 2010 at the University of Pennsylvania. A total of 246 women underwent re-excision because of close margins. Average margin index between groups with and without residual disease in the re-excision specimen was compared using the Student t-test. A receiver operating curve was created using logistic regression to assess the overall diagnostic ability of the margin index on the presence or absence of residual disease.

Results

Of patients who underwent re-excision, 29% of patients had residual disease. We analyzed several cutoff values for margin index, but none proved to be significant predictors of residual disease. Average margin index was significantly higher for patients without residual disease compared with patients with residual invasive cancer but not for patients with residual ductal carcinoma in situ.

Conclusions

In women undergoing BCS for early stage breast cancer at our institution, margin index was not predictive of the presence of residual cancer on re-excision. We hypothesize that the predictive ability of a margin index is likely limited by several factors including the presence of ductal carcinoma in situ and the location and extent of the close margin.     

Surgical,oncologic, and cosmetic differences between oncoplastic and nononcoplastic breast conserving surgery in breast cancer patients

Background

There is a lack of information regarding the safety, complication rate, and cosmetic outcome of oncoplastic breast conserving surgery. The purpose of this study is to evaluate and compare oncoplastic and nononcoplastic procedures.

Methods

A retrospective review was conducted of patients treated with oncoplastic or nononcoplastic lumpectomies. Immediate and long-term complication rates and cosmetic satisfaction were compared.

Results

Of the 142 surgeries, 58 were oncoplastic lumpectomies (40.8%). Oncoplastic patients were younger than nononcoplastic patients (60.9 vs 65.2 years, P = .043). Immediate complications were similar with the exception of nonhealing wounds (oncoplastic = 8.6% vs nononcoplastic = 1.2%, P = .042). Cosmetic complaints were similar, but fat necrosis was more common in the oncoplastic group (25.9% vs 9.5%, P = .009). Time to radiation and number of future biopsies were similar between the groups.

Conclusion

Oncoplastic lumpectomy is a safe alternative to standard lumpectomy for selected breast cancer patients.     

A prospective,randomized, multicenter clinical trial to evaluate the safety and effectiveness of a new lesion localization device

BACKGROUND: The objective was to compare the safety and effectiveness of a new localization device to traditional flexible wires. Safety variables included blood loss, procedure time, pain and complications. Effectiveness variables included placement accuracy, lesion retrieval, histological diagnosis, procedural enhancements, and margin status. METHODS: Twelve sites enrolled 120 patients between June 2000 and June 2001, with 58 randomized to treatment and 62 to control. RESULTS: The two groups were equivalent in device placement accuracy, lesion retrieval, histological diagnosis, blood loss, pain, and complications. There was a significant difference favoring the treatment group for procedural enhancements, (ie, use as a palpable guide and retractor) and operating time. There were significantly fewer positive margins in the treatment group. CONCLUSIONS: This multicenter trial demonstrated equivalent safety and improved effectiveness for the treatment group. The new device demonstrated greater surgeon utility, reduced operative time, and fewer positive margins than the current wires.     

Long-term outcomes in patients with mucinous, medullary, tubular, and invasive ductal carcinomas after lumpectomy

BACKGROUND: Mucinous, medullary, and tubular carcinomas are uncommon types of breast cancer whose rarity does not permit large single-institution studies or randomized trials to define optimal treatments. In this study, we evaluated the long-term outcomes of breast-conserving therapy (BCT) for these subtypes of breast cancer and compared them with those for invasive ductal carcinoma. METHODS: In our institutional database of patients who received BCT from 1965 to 1999, 1,643 patients with stage I to II mucinous (61), medullary (37), tubular (60), and invasive ductal (1,485) histologies were identified. The clinical and pathologic features of the 4 groups were evaluated and compared with respect to local-regional recurrence rates, disease-free survival, and overall survival (OS). RESULTS: No statistically significant differences were found in the local-regional failure rate among the 4 groups (10.6-year median follow-up). Only patients with tubular carcinoma had better 5- and 10-year OS rates (P = .013). In multivariable analysis, factors associated with improved OS included age at or below 50 years, negative nodal status, use of chemotherapy or hormonal therapy, and tubular histology. CONCLUSIONS: BCT for mucinous, medullary, or tubular carcinoma resulted in similar local-regional failure rates to that for invasive ductal carcinoma. Tubular carcinoma patients had the most favorable OS. BCT is an appropriate treatment strategy for early-stage mucinous, medullary, and tubular carcinomas.     

Biopsy findings after breast conservation therapy for early-stage invasive breast cancer

PURPOSE: To determine the patterns and factors predictive of positive ipsilateral breast biopsy after conservation therapy for early-stage breast cancer. METHODS AND MATERIALS: We performed a retrospective review of Stage I-II breast cancer patients initially treated with lumpectomy and radiotherapy between 1977 and 1996, who later underwent post-treatment ipsilateral breast biopsies. RESULTS: A total of 223 biopsies were performed in 193 treated breasts: 171 single and 22 multiple biopsies. Of the 223 biopsies, 56% were positive and 44% were negative for recurrence. The positive biopsy rate (PBR) was 59% for the first and 32% for subsequent biopsies. The median time to the first post-treatment biopsy was 49 months. Of the patients with negative initial biopsy findings, 11% later developed local recurrence. The PBR was 40% among patients with physical examination findings only, 65% with mammographic abnormalities only, and 79% with both findings (p = 0.001). Analysis of the procedure type revealed a PBR of 86% for core and 58% for excisional biopsies compared with 28% for aspiration cytology alone (p = 0.025). The PBR varied inversely with age at the original diagnosis: 49% if >or=51 years, 57% if 36-50 years, and 83% if 180 months after completing postlumpectomy radiotherapy (p = 0.01). The PBR was not linked with recurrence location, initial pathologic T or N stage, estrogen receptor/progesterone receptor status, or final pathologic margins (all p >or= 0.15). CONCLUSION: After definitive radiotherapy for early-stage breast cancer, a greater PBR was associated with the presence of both mammographic and clinical abnormalities, excisional or core biopsies, younger age at the initial diagnosis, and longer intervals after radiotherapy completion.     

Hematoma-Directed Ultrasound-Guided (HUG) Breast Lumpectomy

Background Needle localization breast biopsy (NLBB) is presently the primary means of localizing non-palpable lesions. Disadvantages of NLBB include vasovagal episodes, patient discomfort, and miss rates. Because hematomas naturally fill the cavity after vacuum-assisted breast biopsies (VABB), we hypothesized that ultrasound (US) could be used to find and accurately excise the actual biopsy site of non-palpable breast lesions without a needle. Methods This is a retrospective study from January 2000 to July 2005. Electronic chart review identified patients with non-palpable breast lesions detected by means of mammogram who then underwent lumpectomy via NLBB or the hematoma-directed ultrasound-guided technique (HUG). HUG involved localizing the hematoma with a 7.5-MHz US probe and using the “line of sight” technique straight down toward the chest wall. A block of tissue encompassing the hematoma was then excised. Results Localization procedures were performed in 186 patients—63 (34%) via needle localization and 123 (66%) via HUG. The previous VABB site in 100% of patients was successfully excised using HUG, 65 of 123 (53%) were benign and 58 of 123 (47%) were malignant; margins were positive in 13 of these 58 (22%). NLBB was successful in 100% of patients, 44 of 63 (70%) were benign and 19 of 63 (30%) were malignant; margins were positive in 14 of these 19 (73%). Margin positivity was significantly higher for NLBB than HUG (P = 0.0001, Fisher Exact). Conclusions This study suggests that HUG is more accurate in localizing non-palpable lesions than NLBB. By eliminating the additional procedure needed for NLBB, HUG may also be more time- and cost efficient. HUG makes VABB not only a less invasive diagnostic procedure, but also a localization procedure. Margaret Thompson: Supported by the Virginia Clinton Kelley/Fashion Footwear Association of New York Breast Cancer Research Fellowship Aaron Margulies: Supported by the Susan G. Komen Breast Cancer Clinical Fellowship     

Association of Clinical and Pathologic Variables with Lumpectomy Surgical Margin Status after Preoperative Diagnosis or Excisional Biopsy of Invasive Breast Cancer

Purpose To evaluate the impact of preoperative diagnosis in obtaining negative lumpectomy margins. Materials and Methods Five hundred and thirty five patients who underwent breast conserving therapy for stage I/II cancer from 1971 to 1996 were included in this IRB-approved retrospective analysis. Three hundred and ninety five patients had a defined inked margin status after initial excision. The following factors were evaluated for correlation with margins at initial excision: age (< or >45), grade (3/1 or 2), family history (present/absent), histology (lobular/other), estrogen receptor (ER) status, presence of extensive intraductal carcinoma (EIC), presence of lymphovascular invasion (LVI), and biopsy type (excisional/preoperative). Results Biopsy type (P < 0.0001), EIC (P = 0.002), ER status (P = 0.02), lobular histology (P = 0.02) and age (P = 0.02) were significantly correlated with initial margin status among the entire group. For patients who underwent preoperative diagnostic biopsy, 52% (35/67) had negative initial margins as compared to 29% (94/328) for excisional biopsy. Among patients who underwent preoperative biopsy, only lobular histology (P = 0.04) and LVI (P = 0.04) were related to initial margin status. The rate of re-excision was 34% for patients diagnosed preoperatively versus 61% with excisional biopsy (P < 0.0001). The percentage of patients with negative final margin status was similar with either core/needle or excisional biopsy (79 and 78%, respectively). Conclusions Preoperative diagnosis is the most significant predictor of initial margin status in patients undergoing breast conservation. Patients with lobular histology may require improved preoperative and/or intraoperative assessment to increase the rate of negative margins at initial excision.