First Results of the Primary Outcome of a Phase 2 Prospective Clinical Trial to Assess the Feasibility of Preoperative Radiation Boost in Patients With Breast Cancer.

PURPOSE: A radiation therapy (RT) boost to the tumor bed is an important component of breast-conserving therapy in early breast cancer. This prospective phase 2 study assessed the feasibility of delivering the RT boost before surgery. We hypothesize wound complication rates to be comparable with postoperative RT and the target boost volume to be smaller than standard postoperative RT. METHODS AND MATERIALS: This prospective phase 2 trial accrued 55 patients with clinically node-negative breast cancer eligible for breast-conserving therapy. Patients were treated with preoperative RT boost of 1332 cGy in 4 fractions, followed by lumpectomy and postoperative adjuvant whole breast RT to 3663 cGy in 11 fractions. The primary outcome was to demonstrate the incidence of grade 3 or more wound complications was not inferior to lumpectomy with standard postoperative whole breast RT and boost (6%-20%). We also compared the preop boost volume with a mock boost volume that would have been done after surgery. RESULTS: Fifty-five women were enrolled between June 2021 and October 2022. Median age was 64 years old (range, 40-77 years). Forty-three patients had invasive cancers, and 5 had ductal carcinoma in situ. Median clinical tumor size was 13 mm (range, 5-26 mm). Grade 3 wound dehiscence requiring surgical revision occurred in 1 patient (2%). There were no other grade 3 adverse events. Three patients (6%) had grade 2 infections requiring antibiotics. The target boost volume was significantly lower than mock postoperative volume (11 cc vs 56 cc; P < .001) Cosmetic outcome at the first follow-up was very good or excellent in 87% of patients, and none had poor cosmetic outcomes. CONCLUSION: The use of a preoperative RT boost followed by whole breast RT as administered here resulted in an acceptable primary outcome with a similar rate of postoperative wound complications and smaller boost volume compared with standard postoperative RT. This approach is currently under consideration for cooperative group phase 3 trial.

Long-Term Clinical and Cosmetic Outcomes of Once-Daily Accelerated Partial Breast Irradiation in Early Breast Cancer.

Purpose: Accelerated partial breast irradiation (APBI) is one of the standard treatment options in early-stage node negative breast cancer in selected patients. However, the optimal dose fractionation schedule still represents a challenge. We present the 12-year follow up results of clinical and cosmetic outcomes of once daily APBI with external beam radiation therapy which provides an APBI radiation dose equivalent to the whole breast radiation with a boost. Methods and Materials: From July 2008 to August 2010, we enrolled 34 patients with T1, T2 (< 3cm) N0 to receive once daily APBI with three dimensional conformal radiation therapy (3D-CRT) to a total dose of 49.95 Gy over 15 single daily fractions over 3 weeks at 3.33 Gy per fraction. Ipsilateral breast tumor recurrence (IBTR), acute toxicity, late toxicity and cosmesis was analyzed. The median follow-up for all patients is 144 months (12 years). Results: The median age of the patients was 61 years (range 46-83). Nine patients had ductal carcinoma in situ (DCIS) and 25 patients had invasive cancer. The median size of the tumor with DCIS pathology was 0.5 cm, while median size of the tumor with invasive cancer pathology was 1.0 cm. All of the patients had negative margins and negative nodes. Two IBTR was observed (5.8%). One patient had DCIS at recurrence and other had invasive recurrence. Two patients died due to non-cancer cause. The 12-year actuarial ipsilateral breast recurrence free survival was 93.5% and the 12-year actuarial overall survival was 93.2%. Late Grade 2 toxicity was observed in 6 patients and late grade 3 toxicity was seen in 1 patient. 91% of the patients had excellent to good cosmesis. Conclusions: This novel APBI dosing schema is based on an equivalent dose compared to whole breast radiation plus a tumor bed boost. This once daily APBI scheme is well-tolerated and demonstrates good to excellent cosmetic outcome and low rates of late complications on long term follow-up.

Society of Surgical Oncology Breast Disease Site Working Group Statement on Contralateral Mastectomy: Indications, Outcomes, and Risks.

Rates of contralateral mastectomy (CM) among patients with unilateral breast cancer have been increasing in the United States. In this Society of Surgical Oncology position statement, we review the literature addressing the indications, risks, and benefits of CM since the society's 2017 statement. We held a virtual meeting to outline key topics and then conducted a literature search using PubMed to identify relevant articles. We reviewed the articles and made recommendations based on group consensus. Patients consider CM for many reasons, including concerns regarding the risk of contralateral breast cancer (CBC), desire for improved cosmesis and symmetry, and preferences to avoid ongoing screening, whereas surgeons primarily consider CBC risk when making a recommendation for CM. For patients with a high risk of CBC, CM reduces the risk of new breast cancer, however it is not known to convey an overall survival benefit. Studies evaluating patient satisfaction with CM and reconstruction have yielded mixed results. Imaging with mammography within 12 months before CM is recommended, but routine preoperative breast magnetic resonance imaging is not; there is also no evidence to support routine postmastectomy imaging surveillance. Because the likelihood of identifying an occult malignancy during CM is low, routine sentinel lymph node surgery is not recommended. Data on the rates of postoperative complications are conflicting, and such complications may not be directly related to CM. Adjuvant therapy delays due to complications have not been reported. Surgeons can reduce CM rates by encouraging shared decision making and informed discussions incorporating patient preferences.

Diagnosis, Management, and Surveillance for Patients With PALB2, CHEK2, and ATM Gene Mutations.

BACKGROUND: This study aims to capture clinical and surgical practice patterns of patients with deleterious mutations in partner and localizer of BRCA2 (PALB2), checkpoint kinase 2 (CHEK2) and ataxia telangiesctasia mutated (ATM) genes. MATERIALS AND METHODS: This study is a retrospective chart review of patients with PALB2, CHEK2 or ATM mutations. Patient demographics, testing indications, management decisions, and surveillance strategies were recorded. RESULTS: Sixty-two patients were found to have deleterious mutations: 14 (23%) with a PALB2 mutation, 30 (48%) with a CHEK2 mutation, and 18 (29%) patients with an ATM mutation. Thirty-one (50%) patients have a history of breast cancer. Twenty-three patients were diagnosed and treated prior to genetic testing while 8 patients learned of their mutation status and breast cancer diagnosis simultaneously. Of these 8 patients, 4 sought treatment at our institution, 3 underwent bilateral mastectomy, and 1 patient opted for lumpectomy and surveillance. Thirty-one patients had no history of breast cancer. After genetic diagnosis, 3 of the 9 patients who continued clinical follow-up proceeded with bilateral prophylactic mastectomy within 2 years. Clinical surveillance continued for 23 months on average. CONCLUSION: Most patients who learned of their genetic and breast cancer diagnoses simultaneously underwent bilateral mastectomy, whereas only a third of patients without cancer opted for bilateral prophylactic mastectomy.

The Use of Intraoperative Ultrasound During Breast Conserving Surgery.

OBJECTIVES: The purpose of this study is to evaluate the utilization of intraoperative ultrasound (IOUS) for tumor localization in breast-conserving surgery and to examine its impact on margin positivity and re-excision rates. Additionally, the study seeks to identify factors contributing to surgeon utilization of IOUS. METHODS: A retrospective chart review was conducted of patients with preoperative diagnosis of breast cancer undergoing breast-conserving surgery by breast surgeons at multiple centers within a single healthcare system. Characteristics such as lesion size, palpability, histology, receptor status, and use of neoadjuvant chemotherapy were recorded. Re-excision rates were determined based on localization technique and surgeons' status of breast ultrasound certification. RESULTS: A total of 671 cases were performed, with 322 meeting study inclusion. 57 cases utilized IOUS, 250 utilized preoperative wire-guided localization (WGL), 10 used both methods and 5 cases used neither method. There was no significant difference in re-excision rates between IOUS and WGL or among the four surgeons. Ultrasound-certified surgeons were more likely to utilize IOUS, and re-excision rates trended higher for WGL, which may be clinically significant. CONCLUSION: Increasing familiarity with and utilization of IOUS during breast-conserving surgery may be clinically advantageous over traditional localization techniques. Ultrasound certification may lead to increased use of IOUS among surgeons.

Risk Factors for the Development of Clinical and Subclinical Lymphedema Detected by Bioimpedance Spectroscopy.

BACKGROUND: Breast cancer-related lymphedema can significantly compromise quality of life. Bioimpedance spectroscopy (BIS) measures extracellular fluid in lymphedema. The purpose of this study was to determine the incidence of BIS-detected lymphedema using the L-Dex and identify risk factors associated with a positive score. MATERIALS AND METHODS: We performed a retrospective review of our institutional database to identify patients who underwent L-Dex U400 measurements. Patients with a score of > 10 L-Dex units or with an increase of > 10 units from baseline had a positive score. Clinical lymphedema was determined by documentation in the chart at the time of positive measurement. Otherwise, patients were considered to have subclinical lymphedema. RESULTS: Fifty-three patients met study criteria. Thirty patients (56.6%) underwent mastectomy, 22 (41.5%) axillary lymph node dissection (ALND), and 33 (62.3%) received radiation (RT). Twelve patients (22.6%) had a positive score. There were no differences in age, race, laterality, breast surgery, T stage, N stage, chemotherapy, or RT fields (none, breast only, breast with LNs) in patients with a positive score. ALND was more common (66.7% vs. 34.2%, P= .04). BMI > 30 approached significance (58.3% vs. 29.3%, P= .06). Seven patients had subclinical lymphedema. No differences were identified comparing patients with subclinical lymphedema to those with negative scores. All 5 patients with clinical lymphedema underwent ALND and received nodal RT. CONCLUSION: The combination of ALND and regional nodal RT is strongly associated with development of clinical lymphedema. It is difficult to identify patients at risk for subclinical BIS-detected lymphedema.

Durable Response to PD1 Inhibitor Pembrolizumab in a Metastatic, Metaplastic Breast Cancer.

Metaplastic breast cancer (MBC) is a rare and aggressive subtype of breast cancer. Tumor characteristics typically feature estrogen receptor, progesterone receptor, and HER2-negative, triple-negative breast cancer (TNBC), with a poorer prognosis relative to pure invasive ductal or lobular disease. Resistance to chemotherapy often leads to local recurrence and distant metastasis. Genomic profiling has identified multiple molecular abnormalities that may translate to targetable therapies in MBC. These tumors are known to display higher PD-L1 expressivity than other subtypes of breast cancer, and disease control with pembrolizumab and chemotherapy has been documented. We identify a patient with metastatic, metaplastic TNBC, with mesenchymal components and osseous differentiation, who completed 2 years of pembrolizumab treatment and has remained without evidence of disease after 32 months of observation, while maintaining good quality of life. Future efforts should focus on immunotherapy response with respect to the various subtypes of MBC, and treatment should continue to be incorporated in clinical trials to maximize disease response.

A Three-Dimensional Bioabsorbable Tissue Marker for Volume Replacement and Radiation Planning: A Multicenter Study of Surgical and Patient-Reported Outcomes for 818 Patients with Breast Cancer.

BACKGROUND: Accurate identification of the tumor bed after breast-conserving surgery (BCS) ensures appropriate radiation to the tumor bed while minimizing normal tissue exposure. The BioZorb® three-dimensional (3D) bioabsorbable tissue marker provides a reliable target for radiation therapy (RT) planning and follow-up evaluation while serving as a scaffold to maintain breast contour. METHODS: After informed consent, 818 patients (826 breasts) implanted with the BioZorb® at 14 U.S. sites were enrolled in a national registry. All the patients were prospectively followed with the BioZorb® implant after BCS. The data collected at 3, 6, 12, and 24 months included all demographics, treatment parameters, and provider/patient-assessed cosmesis. RESULTS: The median follow-up period was 18.2 months (range, 0.2-53.4 months). The 30-day breast infection rate was 0.5 % of the patients (n = 4), and re-excision was performed for 8.1 % of the patients (n = 66), whereas 2.6 % of the patients (n = 21) underwent mastectomy. Two patients (0.2 %) had local recurrence. The patient-reported cosmetic outcomes at 6, 12, and 24 months were rated as good-to-excellent by 92.4 %, 90.6 %, and 87.3 % of the patients, respectively and similarly by the surgeons. The radiation oncologists reported planning of target volume (PTV) reduction for 46.2 % of the patients receiving radiation boost, with PTV reduction most commonly estimated at 30 %. CONCLUSIONS: This report describes the first large multicenter study of 818 patients implanted with the BioZorb® tissue marker during BCS. Radiation oncologists found that the device yielded reduced PTVs and that both the patients and the surgeons reported good-to-excellent long-term cosmetic outcomes, with low adverse effects. The BioZorb® 3D tissue marker is a safe adjunct to BCS and may add benefits for both surgeons and radiation oncologists.

5-Year Results of a Prospective Phase 2 Trial Evaluating 3-Week Hypofractionated Whole Breast Radiation Therapy Inclusive of a Sequential Boost.

PURPOSE: To report 5-year outcomes of a phase 2 trial of hypofractionated whole breast irradiation (HF-WBI) completed in 3 weeks, inclusive of a sequential boost. METHODS AND MATERIALS: Women with stage 0-IIIA breast cancer (ductal carcinoma in situ through T2N2a) were enrolled on a prospective, phase 2 trial of accelerated HF-WBI. We delivered a whole breast dose of 36.63 Gy in 11 fractions of 3.33 Gy, with an equivalent dose to the regional nodes when indicated, followed by a tumor bed boost of 13.32 Gy in 4 fractions of 3.33 Gy over a total of 15 treatment days. The primary endpoint was locoregional control; secondary endpoints included acute/late toxicity and physician-assessed and patient-reported breast cosmesis. RESULTS: Between 2009 and 2017, we enrolled 150 patients, of whom 146 received the protocol treatment. Median age was 54 years (range, 33-82) and median follow-up was 62 months. Patients with higher-risk disease comprised 59% of the cohort, including features such as young age (33% ≤50 years), positive nodes (13%), triple-negative disease (11%), and treatment with regional nodal irradiation (11%) and/or neoadjuvant/adjuvant chemotherapy (36%). Five-year estimated locoregional and distant control were 97.7% (95% confidence interval [CI], 93.0%-99.3%) and 97.9% (95% CI, 93.6%-99.3%), respectively. Five-year breast cancer-specific and overall survival were 99.2% (95% CI, 94.6%-99.9%) and 97.3% (95% CI, 91.9%-99.1%), respectively. Acute/late grade 2 and 3 toxicities were observed in 30%/10% and 1%/3% of patients, respectively. There were no grade 4 or 5 toxicities. Physicians assessed breast cosmesis as good or excellent in 95% of patients; 85% of patients self-reported slight to no difference between the treated and untreated breast. CONCLUSIONS: Our phase 2 trial offers one of the shortest courses of HF-WBI; at 5 years of follow-up there continues to be excellent locoregional control and low toxicity with favorable cosmetic outcomes in a heterogeneous cohort of patients.

Oncoplastic breast surgery in the setting of breast-conserving therapy: A systematic review.

Breast-conserving therapy (BCT), or breast-conserving surgery with adjuvant radiation therapy, has become a standard treatment alternative to mastectomy for women with early-stage breast cancer after many long-term studies have reported comparable rates of overall survival and local control. Oncoplastic breast surgery in the setting of BCT consists of various techniques that allow for an excision with a wider margin and a simultaneous enhancement of cosmetic sequelae, making it an ideal breast cancer surgery. Because of the parenchymal rearrangement that is routinely involved in oncoplastic techniques, however, the targeted tissue can be relocated, thus posing a challenge to localize the tumor bed for radiation planning. The goals of this systematic review are to address the challenges, outcomes, and cosmesis of oncoplastic breast surgery in the setting of BCT.

Optimal surgical treatment of breast cancer: implications for local control and survival.

Improvements in the local control of primary breast cancer have been shown to improve long-term survival. The role of surgical therapy in maximizing local control includes: appropriate patient selection for breast conservation; tumor resection with pathologically free margins; careful staging with sentinel node biopsy; appropriate use of axillary dissection; and meticulous surgical technique to achieve these goals. Each component of surgical therapy has the potential for maximizing local control, and therefore for extending survival.

Two case reports of pollicization of a previously syndactylized index finger for congenitally absent thumb.

Two patients with absent thumbs and complicated syndactyly were successfully treated by pollicization of the index finger. Prior surgical release of the index finger syndactyly and then pollicization of that digit carries with it an increased risk of neurovascular compromise, adverse placement of surgical scars, and a stiff or unstable thumb. With caution, very satisfying reconstructive results can nonetheless be attained.

Sternal wound debridement and muscle flap reconstruction: functional implications.

The mortality rate for poststernotomy infection, which occurs in as many as 5% of median sternotomy incisions after cardiovascular surgery, was 37.5% until sternal debridement with muscle or omental flap reconstruction became the standard treatment for this postoperative complication and lowered the mortality rate to just more than 5%. There are few reports in the literature of physical functional deficits and long-term outcome resulting from such reconstruction. The authors evaluated two groups of patients who had undergone coronary bypass surgery at least 6 months earlier. One group had no postoperative complications; the other group had developed marked sternal wound infections that required debridement and pectoralis major or rectus abdominis muscle reconstruction. Both groups underwent pectoralis and rectus muscle strength testing, evaluation of pain and ability to perform those activities of daily living that are dependent on pectoral and rectus muscle function, and completed self-assessment questionnaires. Differences between the two groups were significant (p<0.05) with regard to pain and patient satisfaction with appearance and general functional capacity. Pectoral muscle function and strength were significantly different in patients in whom that muscle was transposed. Rectus muscle strength was not affected by the transposition of a single rectus muscle. Physical morbidity and loss of strength seemed to be related directly to loss of sternal stability stemming from marked infection and debridement rather than from loss of the muscles used in reconstruction.

Measuring normal hand dexterity values in normal 3-, 4-, and 5-year-old children and their relationship with grip and pinch strength.

After surgery for trauma or correction of congenital anomaly, hand function is difficult to evaluate in children because there are no reference norms on children 3 to 5 years old. The purpose of this study was to determine whether reproducible normative values for hand dexterity and grip and pinch strength could be obtained in young children using simple tests that could be administered quickly within the attention span of a 3- to 5-year-old. The Functional Dexterity Test (FDT), a pegboard test validated for adults and older children, seemed to meet our requirements for dexterity. The FDT was administered to a convenience sample of normal children in a prekindergarten school who were grouped according to age: 3-year-olds (n = 17), 4-year-olds (n = 24), and 5-year-olds (n = 22). Hand dominance was determined. The task was demonstrated by 1 of the 2 testers. The child was asked to turn the pegs over in the pegboard without using the free hand or balancing the peg against the chest. Both hands were tested. Grip and pinch strengths were measured in both hands in a consistent manner. All the children were tested with the arm at the side and the elbow at 90 degrees. A dynamometer was used for grip strength and a pinch meter was used to measure key (lateral) and tripod pinch strengths. Means and SDs were calculated for each age group, and the dependent values of dexterity, strength, and dominance were correlated. Dexterity and strength scores were significantly different by age group. A good FDT score in the dominant hand was predictive of a good score in the nondominant hand. Grip and pinch strength correlated poorly with functional dexterity. The normative values established in this study for children in the 3- to 5-year-old range can be referenced for disability estimates and establishing goals for children after surgery or hand injury.

Anatomy of the intrinsic hand muscles revisited: part I. Interossei.

In this article, the anatomic variations in interosseous muscle insertions are described based on a review of the literature and 14 fresh cadaver hand dissections. The findings are correlated and compared with those of a number of other investigators, and the clinical implications are discussed (i.e., in the correction of ulnar deviation in arthritis patients and in the treatment of congenital anomalies of the hand). It is concluded that descriptions of insertion sites of the intrinsic muscles have been oversimplified by previous researchers, and a number of variations are identified through the cadaver dissections. The differing and confusing nomenclature used by other investigators is discussed and simplified. The results of this study indicate that not only are there important distal insertions onto bone and the extensor apparatus, but there is also an additional insertion onto the volar plate ("assemblage nucleus"), as Zancolli reported. It was found that the palmar interossei, generally thought to insert only onto the extensor apparatus, could also insert onto bone and onto the volar plate. Classic teaching is that all dorsal interossei (except the third) have two heads and that all palmar interossei have only one head. In this study, however, 38 percent of the palmar interossei and 75 percent of the dorsal interossei had more than one head. The complexity of the interossei is apparent when as many as three different muscle heads are present, each with a different distal destination.

Anatomy of the intrinsic hand muscles revisited: part II. Lumbricals.

The authors discuss the anatomic variations and the precise origins and insertions of the lumbrical muscles, after dissecting 14 fresh cadavers (56 lumbrical muscles) and reviewing the scant published literature. They compare the findings with those of other investigators, and they describe the lumbrical muscle insertions discovered during the dissections. The authors conclude that descriptions of the origins and insertions of the lumbrical muscles have been oversimplified or not investigated at all, that lumbricals originate variably from the flexor digitorum profundus tendon and may even be bipinnate, and that three different major destinations exist for distal insertion of these intrinsic muscles: bone, volar plate, and extensor apparatus. Previous descriptions have focused only on the lumbrical continuation to the lateral band of the extensor mechanism.