Erin E. Burke

Prophylactic mastectomy: Who needs it, when and why

Prophylactic mastectomy generally occurs in two different patient populations: (1) high‐risk women without breast cancer who undergo bilateral prophylactic mastectomy (BPM) to reduce their risk of developing breast cancer and (2) women with unilateral breast cancer who choose contralateral prophylactic mastectomy (CPM) to prevent cancer in the contralateral breast. The purpose of this article is to review the indications, outcomes, and trends in the use of BPM and CPM. J. Surg. Oncol. 2015 111:91–95.

A comparative analysis of survival outcomes between pancreatectomy and chemotherapy for elderly patients with adenocarcinoma of the pancreas

The survival rates after pancreatectomy for elderly patients with adenocarcinoma of the pancreas remain poor. Elderly patients have increased perioperative mortality rates, higher morbidity rates, and higher rates of continued inpatient nursing care after pancreatectomy. The objective of the current study was to evaluate the outcomes of surgical resection versus chemotherapy (with or without radiotherapy) for elderly patients with potentially resectable adenocarcinoma of the pancreas.

Lymph node evaluation for treatment of adenocarcinoma of the pancreas

BACKGROUND Increased lymph node evaluation has been associated with improved survival rates in patients with pancreatic cancer. We sought to evaluate the trends and factors associated with lymph node examination over time and the effects on survival. METHODS Using the Surveillance, Epidemiology and End Results database, we conducted an analysis of adults with adenocarcinoma of the pancreas who underwent surgical resection. Using the Cochrane Armitage test for trend and logistic regression we identified factors associated with lymph node evaluation. Kaplan-Meier and Cox proportional hazards modeling were used to examine survival. RESULTS We identified 4831 patients who underwent surgical resection from 1990 to 2010. The proportion of patients with 15 or more lymph nodes evaluated increased from 16% to 42% (p < 0.05) and the median number of lymph nodes examined increased from 7 to 15 nodes (p < 0.05) during the study period. Overall, 56% of patients had lymph node metastases; this proportion significantly increased during the study period. Factors that were independently associated with less than 15 lymph nodes evaluated included male gender, receipt of pre-operative radiation therapy, early year of diagnosis, older age, and missing information on tumor grade and size (p < 0.05). Survival rates significantly improved when 15 or more lymph nodes were examined. CONCLUSION We observed a significant increase in the number of lymph nodes evaluated with pancreas cancer resection over time. Lymph node evaluation was significantly associated with patient, tumor, and treatment characteristics. Our results suggest that adequate lymph node evaluation is associated with improved survival.

Contralateral prophylactic mastectomy: are we overtreating patients?

Patients with unilateral breast cancer are at increased risk for developing cancer in the contralateral breast. As a result, some patients choose contralateral prophylactic mastectomy (CPM) to prevent cancer in the contralateral breast. Several studies have reported that the CPM rates have markedly increased in recent years in the United States. In this article, we will discuss recent CPM trends, potential reasons patients choose CPM, outcomes after CPM, and alternative strategies for managing the increased risk of contralateral breast cancer among survivors of unilateral breast cancer. In addition, we will try to determine if women undergoing CPM are adequately informed about their decision.

Surgical Decision Making for Breast Cancer: Hitting the Sweet Spot Between Paternalism and Consumerism

The complexity of surgical decision making for breast cancer has markedly increased in recent years. Most women with early breast cancer currently are eligible for two general surgical treatment choices: mastectomy or breast-conserving surgery (plus radiation therapy). The patients who undergo mastectomy must further decide whether to undergo no reconstruction, immediate reconstruction, or delayed reconstruction. The patients who undergo reconstruction must decide whether to undergo nipple–sparing mastectomy, must choose from a variety of different reconstruction options, and must consider management strategies for their contralateral breast. To complicate the process further, those patients for whom chemotherapy is recommended (patients with estrogen receptor-negative or HER2? breast cancer), must decide whether to receive preor postoperative chemotherapy. Because the oncologic outcomes of all these various options are equivalent, determination of patient preference and satisfaction is extremely important. In their article, Atisha and colleagues evaluate breast satisfaction scores from a large cohort of women who underwent breast cancer surgery using a validated survey instrument. The authors report that women with early-stage breast cancer treated with mastectomy and deep tissue reconstruction are more satisfied with their breasts than women who undergo breast-conserving therapy, mastectomy alone, or mastectomy with reconstruction using implants. Because the survival rates are identical for these procedures, the authors suggest that a focus on patient preferences should help direct how physicians counsel patients. However, measuring patient satisfaction after breast surgery is quite complicated. Long-term breast satisfaction is only one important measurement. The clinician also must consider early outcomes after surgery including personal costs, pain and discomfort, need for unplanned surgical procedures, and return to preoperative physical activities. These outcomes were not reported in the accompanying article. Furthermore, breast reconstruction is associated with significantly higher complication rates than those for either breast-conserving surgery or mastectomy alone. Unfortunately, the current study by Atisha and colleagues actually removed patients who experienced complications from their original treatment group and placed them in a separate category. This methodology certainly biases the results in favor of the treatment groups that otherwise would have had a greater number of complications. In addition to cosmetic and body image outcomes, other important long-term patient satisfaction measures must be considered including overall adjustment to illness, satisfaction with relationships, sexual well-being, fear of recurrence, and chronic pain. Measurement of patient satisfaction also is a time-dependent variable: generally, the longer the time elapsed since surgery, the greater the feelings of psychological adjustment. On the other hand, Atisha and colleagues reported that breast satisfaction scores were significantly lower with increased time since surgery, further illustrating the complicated nature of this issue. Multiple studies have demonstrated that patient satisfaction after breast cancer surgery is strongly associated with the initial decision-making process. For many decades, the predominant model of surgical decision making was paternalistic and driven by the physician’s expertise. Often, the patient’s involvement was reduced to consenting to the proposed treatment. In the past, many surgeons used Society of Surgical Oncology 2014

Trends in the use of pre-operative radiation for adenocarcinoma of the pancreas in the United States.

BACKGROUND The benefit and timing of radiation therapy (RT) for patients undergoing a resection for pancreatic adenocarcinoma remains unclear. This study identifies trends in the use of radiation over a 10-year period and factors associated with the use of pre-operative radiation, in particular. METHODS The Surveillance, Epidemiology and End Results registry was used to identify patients aged ≥18 years with pancreatic adenocarcinoma who underwent a surgical resection between 2000 and 2010. Logistic regression was used to identify time trends and factors associated with the use of pre-operative radiation. RESULTS The overall use of radiation decreased with time among the 8474 patients who met the inclusion criteria. However, the use of pre-operative radiation increased from 1.8% to 3.9% (P ≤ 0.05). Factors significantly associated with receipt of pre-operative radiation were younger age, treatment in more recent years and having an advanced T-stage tumour. The 5-year hazard of death was significantly less for those who received pre-operative radiation versus surgery alone [hazard ratio (HR) 0.64, 95% confidence interval (CI) 0.55-0.74] and for those who received post-operative radiation versus surgery alone (HR 0.69, 95% CI 0.65-0.73). DISCUSSION The use of pre-operative radiation significantly increased during the study period. However, the overall use of pre-operative radiation therapy remains low in spite of the potential benefits.

Pharmacokinetic drug evaluation of talimogene laherparepvec for the treatment of advanced melanoma

ABSTRACT Introduction: Current treatment of advanced melanoma is rapidly changing with the introduction of new and effective therapies including systemic as well as locoregional therapies. An example of one such locoregional therapy is intralesional injection with talimogene laherparepvec (T-VEC). Areas covered: T-VEC has been shown in a number of studies to be an effective treatment for patients with stage IIIB, IIIC and IVM1a melanoma. In this article the effectiveness, pharmacokinetics and safety profile of T-VEC is reviewed. Additionally, new research looking at combinations of T-VEC and systemic immunotherapies is reviewed. Expert opinion: Overall, T-VEC is an easily administered, safe, well tolerated and effective oncolytic viral therapy for the treatment of stage IIIB, IIIC, IVM1a unresectable and injectable metastatic melanoma. Recently published studies are showing promising results when T-VEC is combined with systemic therapy and this may be the way of the not too distant future in how we treat metastatic melanoma. Continued work regarding the use of T-VEC with other systemic agents will provide new and more effective treatment strategies for advanced melanoma.

Prognostic Factors for Metachronous Contralateral Breast Cancer: Implications for Management of the Contralateral Breast

The absolute number of breast cancer survivors who are at risk for metachronous contralateral breast cancer (mCBC) has dramatically increased. The objectives of this study were to identify factors predictive of survival for patients with mCBC and to determine clinicopathological factors predictive of advanced mCBC. Using the Surveillance, Epidemiology, and End Results data base, we identified women, ages 18–80, diagnosed with invasive breast cancer from 1992 to 2010. We excluded patients with bilateral and stage IV primary breast cancer. Patients who developed mCBC ≥12 months from initial diagnosis were identified. Kaplan–Meier methods and Cox proportional hazards modeling were used to determine survival of patients with mCBC. Multivariate logistic regression was utilized to determine factors associated with advanced mCBC. We identified 6,673 patients who developed mCBC during our study period. The median interval between initial breast cancer and mCBC was 5 years. The strongest predictor of overall survival was the nodal status of the mCBC. Other significant prognostic factors included patient age; race; size, nodal status, estrogen receptor status, grade, and type of surgery of the initial breast cancer; grade of the mCBC; and use of radiation therapy for the mCBC. Overall, 25% of mCBCs were node positive. Younger age, black race, and characteristics of the initial breast cancer (increased size, invasive lobular histology, mastectomy treatment, and node‐positivity) were significantly associated with node‐positive mCBC (all p < 0.0.05). The most powerful predictor of survival for patients with mCBC is the nodal status of mCBC. Patients with advanced initial breast cancers are more likely to develop node‐positive mCBC. Adherence to current surveillance and adjuvant therapy guidelines may minimize the risk and mortality of mCBCs.

Bilateral Mastectomy: Doubling Down on Complications?

Complications after breast cancer surgery can result in increased hospitalization, additional surgical and medical interventions, increased costs, and delays in initiating recommended adjuvant treatment. Moreover, complications may lead to long-term emotional distress and patient dissatisfaction. Thus, accurate information regarding the risk, severity, and timing of postoperative complications must be clearly presented to breast cancer patients. In the accompanying study by Silva and colleagues, the authors used the American College of Surgeons National Surgery Quality Improvement Program (NSQIP) to compare the rates of postoperative complications between unilateral and bilateral mastectomy among patients who underwent immediate reconstruction. The authors reported that bilateral mastectomy was associated with longer hospital stays and higher transfusion rates than unilateral mastectomy. Also, bilateral mastectomy with implant reconstruction was associated with a modestly increased reoperation rate. Surprisingly, surgical site infections, prosthesis failure, and medical complications occurred at similar rates between unilateral and bilateral mastectomy. For implant-reconstructed patients, the overall complication rate was 8.8 % after unilateral mastectomy and 10.1 % after bilateral mastectomy. The rates of surgical site complications were 4.2 and 4.6 %, respectively. Determining the rates of postoperative complications after breast cancer surgery can be a frustrating endeavor. Published studies vary widely in regards to the definition, inclusion, and severity of postoperative complications. In addition, the length of follow-up from different studies ranges from a few weeks to a few years. As a result, the published rates of postoperative complications after breast surgery vary dramatically from study to study. Even the results from different studies using the same database seem incongruent. For example, Silva and colleagues report the 30-day surgical site complication rate after bilateral mastectomy and implant-based reconstruction as only 4.6 %. In a very similar study also using NSQIP, Osman and colleagues report the 30-day surgical site complication rate after bilateral mastectomy without reconstruction as 5.8 %. Is the surgical site complication rate really lower for mastectomy after implant-based reconstruction as compared with mastectomy without reconstruction? Also, in the report by Osman and colleagues, the risk of postoperative complications was almost double after bilateral mastectomy as compared to unilateral mastectomy. The 30-day outcomes reported by Silva and colleagues likely substantially underestimate the overall postoperative complication rates after bilateral mastectomy and reconstruction. In a multicenter study from the Cancer Research Network, Barton and colleagues determined the complication rates after bilateral mastectomy. In their patient cohort, 69.1 % underwent implant reconstruction, and almost two-thirds of the women undergoing bilateral mastectomy had at least one complication. In a singlecenter study of 600 patients (58 % had implant reconstruction), Miller and colleagues reported that the overall complication rate after bilateral mastectomy was 41.6 %; on multivariate analysis, bilateral mastectomy was associated with a 2.7 times increased risk of major complications as compared to unilateral mastectomy. In another study that included 593 patients who underwent implant-based reconstruction after bilateral mastectomy, Zion and colleagues reported that 52 % of patients required at least one unanticipated reoperation during a median follow-up of 14 years. Approximately 39 % of all reoperations occurred within 1 year of breast reconstruction. Silva and colleagues appropriately list a number of potential limitations related to NSQIP when it comes to analyzing complication rates after bilateral mastectomy. Society of Surgical Oncology 2015

Surgical management of melanoma

Surgery remains one of the key treatment modalities for melanoma. Wide excision of the primary site with sentinel lymph node biopsy for selected patients has been recognized as the standard surgical approach for patients with early-stage disease. Controversies persist regarding margin width, indications for sentinel lymph node biopsy, and surgical management of regional nodal basins. Additionally, new therapies such as intralesional therapies as well as new systemic therapies are changing the role for surgery in patients with recurrent local–regional as well as metastatic disease. In this article, we discuss the current recommendations as well as the topics of debate in the surgical management of melanoma.