Outcomes of a Multidisciplinary Team in the Management of Patients with Early-Stage Breast Cancer Undergoing Neoadjuvant Chemotherapy at a Community Cancer Center.

Background: The utilization of neoadjuvant chemotherapy (NAC) remains highly variable in clinical practice. The implementation of NAC requires coordination of handoffs between a multidisciplinary team (MDT). This study aims to assess the outcomes of an MDT in the management of early-stage breast cancer patients undergoing neoadjuvant chemotherapy at a community cancer center. Methods: We conducted a retrospective case series on patients receiving NAC for early-stage operable or locally advanced breast cancer coordinated by an MDT. Outcomes of interest included the rate of downstaging of cancer in the breast and axilla, time from biopsy to NAC, time from completion of NAC to surgery, and time from surgery to radiation therapy (RT). Results: Ninety-four patients underwent NAC; 84% were White and mean age was 56.5 yrs. Of them, 87 (92.5%) had clinical stage II or III cancer, and 43 (45.8%) had positive lymph nodes. Thirty-nine patients (42.9%) were triple negative, 28 (30.8%) were human epidermal growth factor receptor (HER-2)+, and 24 (26.2%) were estrogen receptor (ER) +HER-2-. Of 91 patients, 23 (25.3%) achieved pCR; 84 patients (91.4%) had downstaging of the breast tumor, and 30 (33%) had axillary downstaging. The median time from diagnosis to NAC was 37.5 days, the time from completion of NAC to surgery was 29 days, and the time from surgery to RT was 49.5 days. Conclusions: Our MDT provided timely, coordinated, and consistent care for patients with early-stage breast cancer undergoing NAC as evidenced by time to treatment outcomes consistent with recommended national trends.

ACR Appropriateness Criteria® Ductal Carcinoma in Situ.

Ductal carcinoma in situ (DCIS) is a breast neoplasm with potential for progression to invasive cancer. Management commonly involves excision, radiotherapy, and hormonal therapy. Surgical assessment of regional lymph nodes is rarely indicated except in cases of microinvasion or mastectomy. Radiotherapy is employed for local control in breast conservation, although it may be omitted for select low-risk situations. Several radiotherapy techniques exist beyond standard whole-breast irradiation (ie, partial-breast irradiation [PBI], hypofractionated whole-breast radiation); evidence for these is evolving. We present an update of the American College of Radiology (ACR) Appropriateness Criteria® for the management of DCIS. The ACR Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions, which are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review includes an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi technique) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Should resistance exercise be recommended during breast cancer treatment?

Epidemiological evidence has pointed to the benefits of physical activity in reducing breast cancer risk, which in turn has prompted the American Cancer Society (ACS) to make specific recommendations for adopting a life style of physical activity as a guideline for cancer protection. There is also evidence for benefits of physical activity during and after cancer treatments of chemotherapy and radiation therapy. The ACS recommendations for exercise as prevention and for exercise during/after cancer treatment are the same: "that adults engage in at least 30 min of moderate to vigorous physical activity, above usual activities, on 5 or more days of the week; 45-60 min of intentional physical activity are preferable." These recommendations suggest participation in aerobic types of physical activity (e.g. brisk walking, biking). Effects of resistance exercise were not addressed specifically by the ACS but have been found to increase lean body mass in patients undergoing cancer treatment. Also, many women preferred resistance exercise over aerobic exercise during breast cancer treatment. In response to strenuous resistance exercise, however, muscle satellite (progenitor) cells are activated to reenter the cell cycle and proliferate. Satellite cells can then contribute their nuclear material into the fiber to facilitate muscle repair, regeneration, and hypertrophy. Cancer therapy damages rapidly dividing cells and thus has the potential to target satellite cells that enter into the cell cycle. Although satellite cells are self-renewing, they are not completely replenished over the lifespan so losses in this progenitor population via resistance exercise and cancer therapy may impair the maintenance of muscle mass with aging. Before recommending resistance training during breast cancer treatment, we must have more information about cancer treatment effects on activated satellite cells in human studies.

Multi-institutional experience using the MammoSite radiation therapy system in the treatment of early-stage breast cancer: 2-year results.

PURPOSE: To present a retrospective multi-institutional experience of patients treated with the MammoSite radiation therapy system (RTS). METHODS AND MATERIALS: Nine institutions participated in a pooled analysis of data evaluating the clinical experience of the MammoSite RTS for delivering accelerated partial breast irradiation. Between 2000 and 2004, 483 patients were treated with the MammoSite RTS to 34 Gy delivered in 10 fractions. Treatment parameters were analyzed to identify factors affecting outcome. RESULTS: Median follow-up was 24 months (minimum of 1 year). Overall, infection was documented in 9% of patients, but the rate was only 4.8% if the catheter was placed after lumpectomy. Six patients (1.2%) experienced an in-breast failure; four failures occurred remote from the lumpectomy site (elsewhere failure). Cosmetic results were good/excellent in 91% of patients. Treatment parameters identified as significant on univariate analysis were tested in multivariate regression analysis. The closed-cavity placement technique significantly reduced the risk of infection (p = 0.0267). A skin spacing of <6 mm increased the risk of severe acute skin reaction (p = 0.0178) and telangiectasia (p = 0.0280). The use of prophylactic antibiotics reduced the risk of severe acute skin reaction (p < 0.0001). The use of multiple dwell positions reduced the risk of severe hyperpigmentation (p = 0.0278). Infection was associated with an increased risk of fair or poor overall cosmesis (p = 0.0009). CONCLUSIONS: In this series of patients, the MammoSite RTS seems to have acceptable toxicity rates and cosmetic outcomes, comparable to those with whole-breast radiotherapy. On the basis of these data, the closed-cavity placement technique, use of prophylactic antibiotics, use of multiple dwell positions, and a minimum skin spacing of 6 mm seem to improve patient outcome.

Long-term outcome and toxicity in a Phase I/II trial using high-dose-rate multicatheter interstitial brachytherapy for T1/T2 breast cancer.

PURPOSE: To present an updated analysis of survival, recurrence rate, and toxicity for a cohort of women with early-stage breast cancer treated with high-dose-rate interstitial brachytherapy for accelerated partial breast irradiation. METHODS AND MATERIALS: From August 1997 to July 2001, a total of 32 women with 33 breast cancers were treated with interstitial high-dose-rate brachytherapy after breast-conserving surgery as part of a Phase I/II protocol. All patients had T1-2 tumors with < or b=3 axillary nodes positive, nonlobular histology, negative surgical margins, and no evidence of extracapsular lymph node extension. Multiple brachytherapy catheters were used and radiation was delivered with a high activity (3-10Ci) (192)Ir source placed via remote after loader. Dose was prescribed to the tumor bed plus a 2 cm margin. A total of 3400 cGy was delivered in 10 fractions of 340 cGy each given twice daily over 5 days. Toxicities (skin, subcutaneous tissue, pain, fat necrosis) were evaluated by Radiation Therapy Oncology Group criteria; cosmesis was assessed using a previously published scale. Toxicity scores were separated into four followup intervals: < or =6 months, >6 months and < or =2 years, >2 and < or =5 years, and >5 years. RESULTS: The actuarial local recurrence rate was 6.1% at 5 years with the last measured event at 70.5 months. A total of three treatment failures were observed at 25.8, 39.9, and 70.5 months of followup. All three were elsewhere failures within the treated breast. One patient died after 90.0 months of followup secondary to a subsequently diagnosed small-cell lung cancer. For the purpose of analysis, toxicity scores were assigned to each of four followup intervals: < or =6 months, >6 but < or =24 months, >24 but < or =60 months, and >60 months. Fat necrosis was not seen in the first 6 months after treatment, then appeared in 27.3% of patients from 6 to 24 months, 28.1% from 24 to 60 months, and 17.9% beyond 60 months. Skin toxicity appeared to stabilize with longer followup: the percentage of patients showing any degree of skin toxicity was 69.7%, 33.3%, 40.6%, and 28.6% at each successive time interval. Subcutaneous toxicity increased beyond 60 months: moderate to severe subcutaneous toxicity was seen in 15.2%, 18.2%, 18.8%, and 35.7% of patients successively. The percentage of patients with less than excellent cosmetic outcome improved beyond 60 months (21.2%, 21.2%, 21.9%, and 11.1% successively). Only 1 patient experienced more than mild pain at any time. The percentage of patients experiencing any degree of pain improved over time (30.3%, 33.3%, 18.8%, 17.9%). CONCLUSIONS: Our series showed a local recurrence rate of 6.1% at 5 years, which is comparable to that seen in conventional whole breast series. Fat necrosis was found in more than half the cohort. Fat necrosis, pain, and cosmesis appeared to improve with longer followup, whereas subcutaneous toxicity worsened and skin toxicity stabilized.

Persistent seroma after intraoperative placement of MammoSite for accelerated partial breast irradiation: incidence, pathologic anatomy, and contributing factors.

PURPOSE: To investigate the incidence of, and possible factors associated with, seroma formation after intraoperative placement of the MammoSite catheter for accelerated partial breast irradiation. METHODS AND MATERIALS: This study evaluated 38 patients who had undergone intraoperative MammoSite catheter placement at lumpectomy or reexcision followed by accelerated partial breast irradiation with 34 Gy in 10 fractions. Data were collected regarding dosimetric parameters, including the volume of tissue enclosed by the 100%, 150%, and 200% isodose shells, dose homogeneity index, and maximal dose at the surface of the applicator. Clinical and treatment-related factors were analyzed, including patient age, patient weight, history of diabetes and smoking, use of reexcision, interval between surgery and radiotherapy, total duration of catheter placement, total excised specimen volume, and presence or absence of postprocedural infection. Seroma was verified by clinical examination, mammography, and/or ultrasonography. Persistent seroma was defined as seroma that was clinically detectable >6 months after radiotherapy completion. RESULTS: After a median follow-up of 17 months, the overall rate of any detectable seroma was 76.3%. Persistent seroma (>6 months) occurred in 26 (68.4%) of 38 patients, of whom 46% experienced at least modest discomfort at some point during follow-up. Of these symptomatic patients, 3 required biopsy or complete cavity excision, revealing squamous metaplasia, foreign body giant cell reaction, fibroblasts, and active collagen deposition. Of the analyzed dosimetric, clinical, and treatment-related variables, only body weight correlated positively with the risk of seroma formation (p = 0.04). Postprocedural infection correlated significantly (p = 0.05) with a reduced risk of seroma formation. Seroma was associated with a suboptimal cosmetic outcome, because excellent scores were achieved in 61.5% of women with seroma compared with 83% without seroma. CONCLUSION: Intraoperative placement of the MammoSite catheter for accelerated partial breast irradiation is associated with a high rate of clinically detectable seroma that adversely affects the cosmetic outcome. The seroma risk was positively associated with body weight and negatively associated with postprocedural infection.

MammoSite excision volume as a predictor for residual disease.

BACKGROUND: The MammoSite catheter is a brachytherapy device used for accelerated partial breast irradiation. Currently, it is available as 2 spherically shaped balloons meant to fill 70-cc and 120-cc cavity volumes. This study was designed to define the relation of these excision volumes to the likelihood of microscopically detectable, residual disease based on tumor size, margin status, patient age, and histology. METHODS: The study data base was comprised of 531 patients with Stage 0, I, and II breast carcinoma (using American Joint Committee on Cancer staging criteria) who received breast-conserving therapy and underwent surgical reexcision. Patients in the data base were stratified based on the volume of their initial excision: < or = 70 cc versus > 70 cc and < or = 120 cc versus > 120 cc. RESULTS: Surgical margin size was found to be a strong predictor of residual disease both for patients with smaller excision volumes (P = 0.0014) and patients with larger excision volumes (P = 0.0003); histology (extensive intraductal component [EIC] or pure ductal carcinoma in situ [DCIS]) also was a strong predictor. Tumor size was significant only for the larger volume group (P = 0.029). On multivariate analysis, only histology and initial margin status were significant correlates with residual disease. The adjusted odds ratio for residual disease with pure DCIS was 0.79, and the adjusted odds ratio for invasive ductal or lobular carcinoma (IDC/ILC) without EIC was 0.44 relative to IDC/ILC with EIC (P = 0.008). The adjusted odds ratio for residual disease with a positive initial margin versus a negative initial margin was 2.65 (P < or = 0.0001). CONCLUSIONS: For excisions amenable to use of the MammoSite catheter, a margin > or = 1.0 mm appeared to afford at most a 35% risk of microscopically detectable residual tumor. Evidence of EIC on excision of IDC/ILC connoted a significantly higher risk. Age did not appear to be predictive for residual disease.

Encephalopathy as a predictor of magnetic resonance imaging abnormalities in asphyxiated newborns.

Basal ganglia abnormalities on magnetic resonance imaging predict neurodevelopmental impairment in newborns with perinatal depression. We determined the value of a clinical encephalopathy score as a predictor of abnormal magnetic resonance imaging results in newborns with perinatal depression. We assigned a neonatal encephalopathy score to 101 newborns. The encephalopathy score, based on alertness, feeding, tone, respiratory status, reflexes, and seizure activity, was assigned once daily. The maximum score from the first 3 days of life was compared with abnormal magnetic resonance imaging results present globally or solely in the basal ganglia.Eighty-one percent of patients manifested abnormalities on any magnetic resonance imaging sequence, and 37% manifested abnormalities in the basal ganglia alone. The encephalopathy score correlated well with magnetic resonance imaging abnormalities in the basal ganglia (Spearman Rho = 0.335, P < 0.0001). Newborns with mild and severe encephalopathy had likelihood ratios of 0.41 and 7.4, respectively, for abnormal basal ganglia magnetic resonance imaging results. Newborns with moderate encephalopathy (composing 47% of the cohort) manifested basal ganglia abnormalities with a likelihood ratio of 0.785. Severe clinical encephalopathy correlates with abnormal basal ganglia magnetic resonance imaging results, and mild encephalopathy correlates with a normal magnetic resonance imaging result. However, standard clinical criteria do not alter the prior risk of abnormal basal ganglia magnetic resonance imaging results for newborns with moderate encephalopathy.