Recurrence and Survival Rates for 1400 Early Breast Tumors Treated with Intraoperative Radiation Therapy (IORT).

INTRODUCTION: Intraoperative radiotherapy (IORT) permits accurate delivery of radiation therapy directly to the tumor bed. We report local, regional, and distant recurrence data along with overall and breast cancer-specific survival for 1400 tumors treated with x-ray IORT. METHODS: A total of 1367 patients with 1400 distinct tumors were enrolled in a registry trial. All received breast conservation surgery and low-energy 50 kV x-ray IORT. To be eligible for excision plus IORT as the only local treatment, histopathology had to confirm tumor size ≤30 mm, margins ≥2 mm, negative lymph nodes, and no extensive lymphovascular invasion. Patients who failed any parameters were referred for additional surgery and/or whole breast radiation therapy (WBRT). RESULTS: There were 64 ipsilateral local recurrences, 60 were in the IORT only group, 7 axillary recurrences, and 7 distant recurrences. Forty-one local recurrences were within the same quadrant as the index cancer. Twenty-three were in different quadrants. With 62 months of median follow-up, the 5-year Kaplan-Meier probability of any event for all 1400 tumors was 5.27%. For 1175 patients who received IORT only, it was 5.98%. For favorable subtypes, it ranged from 2.41 to 4.31%. Multivariate analysis revealed that biologic subtype luminal A and the addition of WBRT significantly reduced the risk of local recurrence. CONCLUSIONS: The local, regional, and distant recurrence rates observed were comparable to those reported in the literature for IORT but higher than those reported for standard forms of WBRT, hypofractionated treatment, or APBI. IORT benefits include convenience, decreased exposure to medical environments, and low complication rates.

Autologous mastectomy reconstruction: Communication among the breast surgery team to maximize aesthetic and oncologic outcome.

Mastectomy breast reconstruction with autologous tissue is challenging. Oncologic and aesthetic goals face previous surgical scars, radiation, chemotherapy, or other comorbidities. We describe a simple approach for autologous mastectomy reconstruction so that breast and plastic and reconstructive surgeons can maximize aesthetic outcomes and minimize wound complications. A retrospective chart review was done on patients who underwent mastectomy and autologous reconstruction. The surgical flight plans were reviewed to delineate an approach, and pre- and postoperative photographs were examined to create a step-by-step process. The most encountered mastectomy and autologous flap reconstruction scenarios were categorized to create a step-by-step process. Successful autologous mastectomy reconstruction to optimize aesthetic outcome and minimize complications requires team communication. Creation of a surgical flight plan using information from the physical examination, MRI and adjunctive imaging, and preoperative photographs is imperative. Thoughtful incision choice and exposure approach are paramount.

Reverse Cascade Screening for Familial Hypercholesterolemia.

PROBLEM: Cardiovascular disease (CVD) is the leading cause of death in the U.S. and in most Western countries. Early identification and treatment of individuals with elevated levels of atherogenic cholesterol, a major contributor to CVD, have been shown to be effective and safe in reducing premature morbidity and mortality, especially in familial hypercholesterolemia (FH). Cholesterol screening of youth also provides a unique means of identifying affected family members through reverse cascade screening (RCS). ELIGIBILITY CRITERIA: A PubMed review of all relevant articles from 2000 to 2016 was conducted of familial hypercholesterolemia and cholesterol screening of youth. RESULTS: We provide an overview of cholesterol screening, outline the role of the pediatric nurse in the lipid clinic, and discuss effectiveness and potential barriers, including cost and confidentiality considerations of RCS. CONCLUSIONS: Early identification and effective intervention of youth with FH, including adoption of a heart-healthy lifestyle, has the potential of 1) markedly reducing or eliminating atherosclerotic cardiovascular disease and related events in future generations and 2) provides a unique means of identifying affected family members. IMPLICATIONS: Pediatric nurses play a vital role in the education and care coordination of children diagnosed with FH and screening of relatives. Identification of a child with FH with effective screening of relatives combines the benefits of universal and cascade screening, and has the potential of detecting all living cases of FH. While potentially providing significant benefit to those at risk for premature CVD, a RCS program needs to carefully consider ethical, psychological, and financial implications as well.

Intraoperative Radiation Therapy (IORT): A Series of 1000 Tumors.

BACKGROUND: Two prospective, randomized trials, TARGIT-A and ELIOT, have shown intraoperative radiation therapy to be a safe alternative, with a low-risk of local recurrence, compared with whole breast radiation therapy, following breast-conserving surgery, for selected low-risk patients. We report the first 1000 tumors treated with this modality at our facility. METHODS: A total of 1000 distinct breast cancers in 984 patients (16 bilateral) were treated with breast conserving surgery and X-ray IORT from June 2010 to August 2017. Patients were enrolled in an IORT registry trial. Local recurrence was the primary endpoint. RESULTS: There have been 28 ipsilateral local recurrences, ten DCIS and 18 invasive. Four local recurrences were within the IORT field, 13 outside of the IORT field but within the same quadrant as the index cancer, and 11 were new cancers in different quadrants. There have been four regional nodal recurrences and one distant recurrence. There have been no breast cancer related deaths and 14 non-breast cancer deaths. With a median follow-up of 36 months, Kaplan-Meier analysis projects 3.9% of patients will recur locally at 4 years. This includes all ipsilateral events in all quadrants. CONCLUSIONS: The local, regional, and distant recurrence rates observed in this trial were comparable to those of the prospective randomized TARGIT-A and ELIOT trials. The low complication rates previously reported by our group as well as the low recurrence rates reported in this study support the cautious use and continued study of X-ray IORT in women with low-risk breast cancer.

Intraoperative Radiation Using Low-Kilovoltage X-Rays for Early Breast Cancer: A Single Site Trial.

INTRODUCTION: Two prospective, randomized trials, TARGIT-A and ELIOT, have shown intraoperative radiation therapy (IORT) to be a safe alternative to whole breast radiation therapy following breast-conserving surgery for selected low-risk patients. However, minimal data are available about the clinical effectiveness of this modality of treatment using the Xoft® Axxent® Electronic Brachytherapy (eBx®) System®. METHODS: A total of 201 patients with 204 early-stage breast cancers were enrolled in a prospective X-ray IORT trial from June 2010 to September 2013. All tumors were treated with breast-conserving surgery and IORT. Data were collected at 1 week, 1 month, 6 months, 1 year, and yearly thereafter. RESULTS: With a median follow-up of 50 months, there have been seven ipsilateral breast tumor events (IBTE), no regional or distant recurrences, and no breast cancer-related deaths. One IBTE was within the IORT field, four outside of the IORT field but within the same quadrant as the index cancer, and two were new biologically different cancers in different quadrants. Three events were in patients who deviated from the protocol criteria. Kaplan-Meier analysis projects that 2.9% of patients will recur locally at 4 years. CONCLUSIONS: Recurrence rates observed in this trial were comparable to those of the TARGIT-A and ELIOT trials as well as the retrospective TARGIT-R trial. The low complication rates previously reported by our group as well as the low recurrence rates reported in this study support the cautious use and continued study of IORT in selected women with low-risk breast cancer.

Acute and Chronic Complications in Patients with Ductal Carcinoma in Situ Treated with Intraoperative Radiation Therapy.

Intraoperative radiation therapy (IORT) delivers radiation therapy directly to the tumor bed at the time of surgery. Minimal data are available regarding IORT complications in patients diagnosed with ductal carcinoma in situ (DCIS) using the Xoft® Axxent eBx® System. 146 patients with pure DCIS received X-ray based IORT therapy using the Xoft® Axxent eBx® System at Hoag Memorial Hospital Presbyterian between June 2010 to April 2016 and were accrued to an IORT data registry study. The protocols were approved by the institutional review board and met the guidelines of their responsible governmental agency. Data were collected at 1 week, 1 month, 6 months, 1 year, and thereafter yearly. Acute complications were defined as those occurring within the first month. Chronic complications were those that persisted beyond 6 months. Acute complications were observed in 18% of patients and included hematomas that required drainage, an infection treated with antibiotics, and erythema. Chronic complications were observed in 12% of patients and included a seroma, fibrosis and hyperpigmentation. The majority of acute and chronic problems were mild (Grade I). If Grade I erythema, fibrosis, and hyperpigmentation are not included, only 11/146 patients (7.5%) had significant complications. The rate of acute and chronic complications from X-ray IORT in DCIS patients was low compared to historical toxicity rates observed in DCIS patients treated with whole breast irradiation. Our data indicate that X-ray IORT can be utilized safely in patients diagnosed with DCIS.

Acute and Chronic Complications in Breast Cancer Patients Treated with Intraoperative Radiation Therapy.

INTRODUCTION: Intraoperative radiation therapy (IORT) permits the delivery of radiation therapy directly to the tumor bed at the time of surgery. Minimal data are available about the complications associated with this modality of treatment using the Xoft(®) Axxent Electronic Brachytherapy (Axxent) System. METHODS: A total of 702 patients who received IORT using the Xoft(®) Axxent System at Hoag Memorial Hospital Presbyterian between June 2010-February 2016 were accrued in an IORT data registry study. The prospective and retrospective protocols were approved by the institutional review board and met the guidelines of their responsible governmental agency. Data were collected at 1 week, 1 month, 3 months, 6 months, 1 year, and thereafter yearly. Acute complications were defined as those occurring within the first month. Chronic complications were those that persisted beyond 6 months. RESULTS: Acute complications were observed in 21 % of patients and included hematomas that required drainage, seromas requiring drainage more than 3 times, infections treated with antibiotics or surgery, necrosis requiring surgery, and erythema. Chronic complications were observed in 13 % of patients and included seromas, fibrosis, and hyperpigmentation. The majority of acute and chronic problems from IORT were mild. If grade I erythema, fibrosis, and hyperpigmentation were removed, only 32 of 702 (4.6 %) had significant complications. Our complication rates were comparable to those of the TARGIT trial. CONCLUSIONS: IORT is a modality that safely delivers radiation therapy to patients diagnosed with breast cancer. This technique allows women who cannot (or decline to) undergo whole breast radiation to consider breast-conserving therapy rather than mastectomy.

Oncoplastic breast conservation surgery: the new paradigm.

Oncoplastic surgery combines plastic surgical techniques with sound surgical oncologic principles. The goal is to completely excise the cancer, with wide surgical margins while maintaining or improving cosmesis. For large, poorly defined, or unfavorably situated tumors, standard lumpectomies may lead to unacceptable cosmetic results in addition to close or involved resection margins. Similar problems may occur for smaller tumors in small breasts. Integration of the two surgical disciplines avoids or minimizes poor cosmetic results after wide excision. It increases the number of women who can be treated with breast-conserving surgery by allowing larger breast excisions with more acceptable cosmetic results. Oncoplastic surgery requires a multidisciplinary approach and thorough preoperative planning. It is absolutely necessary to enlist the cooperation and coordination of surgical oncology, plastic surgery, radiology, pathology, medical oncology, and radiation oncology. Oncoplastic surgery requires a philosophy that the appearance of the breast after tumor excision is important.

A randomized prospective study of lumpectomy margin assessment with use of MarginProbe in patients with nonpalpable breast malignancies.

BACKGROUND: The presence of tumor cells at the margins of breast lumpectomy specimens is associated with an increased risk of ipsilateral tumor recurrence. Twenty to 30 % of patients undergoing breast-conserving surgery require second procedures to achieve negative margins. This study evaluated the adjunctive use of the MarginProbe device (Dune Medical Devices Ltd, Caesarea, Israel) in providing real-time intraoperative assessment of lumpectomy margins. METHODS: This multicenter randomized trial enrolled patients with nonpalpable breast malignancies. The study evaluated MarginProbe use in addition to standard intraoperative methods for margin assessment. After specimen removal and inspection, patients were randomized to device or control arms. In the device arm, MarginProbe was used to examine the main lumpectomy specimens and direct additional excision of positive margins. Intraoperative imaging was used in both arms; no intraoperative pathology assessment was permitted. RESULTS: In total, 596 patients were enrolled. False-negative rates were 24.8 and 66.1 % and false-positive rates were 53.6 and 16.6 % in the device and control arms, respectively. All positive margins on positive main specimens were resected in 62 % (101 of 163) of cases in the device arm, versus 22 % (33 of 147) in the control arm (p < 0.001). A total of 19.8 % (59 of 298) of patients in the device arm underwent a reexcision procedure compared with 25.8 % (77 of 298) in the control arm (6 % absolute, 23 % relative reduction). The difference in tissue volume removed was not significant. CONCLUSIONS: Adjunctive use of the MarginProbe device during breast-conserving surgery improved surgeons' ability to identify and resect positive lumpectomy margins in the absence of intraoperative pathology assessment, reducing the number of patients requiring reexcision. MarginProbe may aid performance of breast-conserving surgery by reducing the burden of reexcision procedures for patients and the health care system.

Breast cancer recurrence after inadvertent malpositioning of a partial breast radiation catheter.

Accelerated partial breast irradiation (APBI) is an alternative to receiving whole breast radiation in carefully selected patients. Because breast cancer local recurrence rates are low and follow-up has been short-term, the exact cause of recurrences after APBI has been difficult to evaluate. We report the first case of documented radiation balloon catheter malpositioning that resulted in local recurrence. Patients undergo CT imaging of the breast after radiation balloon catheter placement for radiotherapy treatment planning, which evaluates adequate conformance of the balloon to the surrounding breast parenchyma and confirms a >7 mm distance between the balloon surface and the skin surface. Although true local recurrences are rare in appropriately selected partial breast irradiation candidates, inadvertent malpositioning of the radiation treatment catheter can increase the risk. This case is presented to illustrate the importance of comparing CT radiation planning images, with treatment catheter in place, to the original diagnostic breast imaging studies to confirm proper catheter positioning (in addition to measuring balloon to skin distance and conformance) prior to initiating radiotherapy.

Analyzing the risk of recurrence after mastectomy for DCIS: a new use for the USC/Van Nuys Prognostic Index.

BACKGROUND: Patients with ductal carcinoma in situ (DCIS) who are treated with mastectomy seldom recur locally or with metastatic disease. When patients with DCIS recur with invasive cancer, they are upstaged and their lives are threatened. We questioned whether histopathologic data could be used to predict these infrequent events. METHODS: We reviewed a prospective database of 1,472 patients with pure DCIS. All patients were scored from 4 to 12 using the USC Van Nuys Prognostic Index, an algorithm based on DCIS size, nuclear grade, necrosis, margin width, and patient age. Probabilities of recurrence and death were calculated using the Kaplan-Meier method. RESULTS: A total of 496 patients with pure DCIS were treated with mastectomy. None received any form of postmastectomy adjuvant treatment. Average follow-up was 83 months. Eleven patients developed recurrences, all of whom scored 10-12 using the USC/VNPI. No patient who scored 4-9 recurred. All 11 patients who recurred had multifocal disease and comedo-type necrosis. The probability of disease recurrence after mastectomy for patients scoring 10-12 was 9.6% at 12 years, compared with 0% for those scoring 4-9. There was no difference in overall survival. CONCLUSIONS: There were no recurrences among mastectomy patients who scored 4-9 using the USC/VNPI. Patients scoring 10-12 were significantly more likely to develop recurrence after mastectomy. At risk were young patients with large, high-grade, and multifocal or multicentric tumors. For every 100 patients with USC/VNPI scores of 10-12, 10 patients will recur by 12 years and 2-3 will develop metastatic disease.

Invasive local recurrence increased after radiation therapy for ductal carcinoma in situ.

BACKGROUND: It is thought that equal numbers of invasive and noninvasive recurrences develop after conservative treatment for ductal carcinoma in situ. We analyzed our data to see if this was true. METHODS: A prospective database of 878 conservatively treated patients with ductal carcinoma in situ was analyzed. RESULTS: Among 551 excision patients, there were 88 recurrences. Thirty-five percent were invasive. Among 327 excision plus radiotherapy patients, there were 59 recurrences. Fifty-three percent were invasive. In an attempt to predict which patients develop invasive recurrences, prolonged time to recurrence was the only statistically significant factor. CONCLUSIONS: The median time to local recurrence for irradiated patients was more than twice as long when compared with nonirradiated patients, during which there is more time for local recurrence to progress to invasion. Irradiated patients had more breast scarring, making diagnosis by palpation and mammography harder. Irradiated patients develop invasive recurrences at a statistically higher rate than nonirradiated patients. Follow-up evaluation with magnetic resonance imaging should be considered.

Healing patterns in anogenital injuries: a longitudinal study of injuries associated with sexual abuse, accidental injuries, or genital surgery in the preadolescent child.

OBJECTIVE: To study healing patterns of anogenital trauma in prepubescent children. METHODS: A prospective 10-year study was conducted of 94 children who had anogenital trauma and were followed to healing and documented using a colposcope with 35-mm camera attachment. RESULTS: The 13 boys and 81 girls were referred with injuries as a result of sexual assault or anogenital trauma. Hymenal injuries occurred in 37 cases; 2 transections healed after surgery, and 15 persisted unchanged. Partial tears, hymenal abrasions, or hematomas healed completely or with minor nonspecific changes. Of the 47 injuries to the posterior fourchette, 22 abrasions, hematomas, or tears healed completely; 12 tears healed with vascular changes; 2 developed labial fusions; 10 lacerations required surgery; and 6 scarred and 4 healed with vascular changes. Only 2 of 39 cases of perihymenal trauma healed with vascular changes. All 17 cases of labial trauma healed completely. Anal trauma healed completely in 29 of 31 with scarring occurring in only 2 cases that required surgery. CONCLUSIONS: Anogenital trauma heals quickly, often without residua. Of the 94 cases, there were diagnostic anatomic changes in the 15 cases of hymenal transections (2 other cases healed completely with surgical reconstruction), 6 cases after surgical repair of posterior fourchette, and 2 cases of anal scarring after surgery.

Appearance of the genitalia in girls selected for nonabuse: review of hymenal morphology and nonspecific findings.

STUDY OBJECTIVE: To review all existing studies of genital anatomy in girls selected for nonabuse, clarify terminology used to describe hymenal morphology and nonspecific findings, and test consensus terminology in the reevaluation of hymenal morphology and nonspecific findings in 147 premenarchal girls selected for nonabuse. METHODS: Over six months, the authors identified and evaluated 147 premenarchal girls without history of sexual abuse who were referred for gynecological examination. Parents and patients were screened for possible abuse or significant past medical or behavioral history, and each girl was interviewed and then received a complete examination including a genital examination documented by colposcopy with both 35 mm camera and video capabilities. Using established terminology(1) each case was then independently reviewed and hymenal morphology and nonspecific findings documented. RESULTS: The study population consisted of 147 premenarchal girls; 76.9% were Hispanic, 12.3% African-American, and 10.3% Caucasian. Subjects had a mean age of 63 months (+/minus sign 38). Hymenal configurations included: annular (concentric) 53%, crescentic (posterior rim) 29.2%, sleeve-like (redundant) 14.9%, septate 2%, and other (imperforate, cribriform) < 1%. Nonspecific findings included peri-hymenal bands, 91.8%; longitudinal intravaginal ridges, 93.8%; hymenal tags, 3.4%; hymenal bumps/mounds, 34%; linea vestibularis, 19%; ventral hymenal cleft/notch at 12 o'clock in 79% of annular or redundant hymens; ventral cleft/notch not at 12 o'clock, 19%; failure of midline fusion, 0.6%; hymenal opening size > 4 mm, 30.6%; erythema, 48.9%; change in vascularity, 37.4%; labial adhesions, 15.6%; posterior hymenal notch/cleft (partial), 18.3%; posterior notch/cleft (complete), 0%; posterior hymenal concavity or angularity, 29.5%. In addition, each case was assessed for the presence of a thickened (45.5%) or irregular (51.7%) and narrowed (22.4%) hymenal edge. Each case was also reviewed for exposed intravaginal anatomy (93%). CONCLUSIONS: The authors concluded that improved techniques and photo documentation have provided examiners with a better understanding of hymenal morphology and that nonspecific genital findings are commonly found in a population of girls selected for nonabuse. A thorough understanding of normal studies and a consistent application of established terminology can prevent the misinterpretation of nonspecific or congenital findings as posttraumatic changes.