The Development of Investigator-Initiated Clinical Trials in Surgical Oncology.

Investigator-initiated trials (IITs) are designed by principal investigators who identify important, unaddressed clinical gaps and opportunities to answer these questions through clinical trials. Surgical oncologists are poised to lead IITs due to their multidisciplinary clinical practice and substantial research background. The process of developing, organizing, and implementing IITs is multifaceted and involves important steps including (but not limited to) navigating regulatory requirements, obtaining funding, and meeting enrollment targets. Here, the authors explore the steps, methodology, and barriers of IIT development by surgical oncologists and highlight the importance of IITs in oncology.

Completion Lymph Node Dissection for Melanoma Before and After the Multicenter Selective Lymphadenectomy Trial-II in the United States.

BACKGROUND: The Multicenter Selective Lymphadenectomy Trial-II (MSLT-II) revealed completion lymph node dissection (CLND) after positive sentinel lymph node biopsy (SLNB) did not improve melanoma-specific survival compared with surveillance. Given these findings and the morbidity associated with CLND, this study investigated trends in rates and predictors of CLND after MSLT-II. METHODS: Analysis of the National Cancer Database was performed for all patients aged ≥18 years with melanoma and a positive SLNB for 2012-2019. Rates of CLND before and after publication of MSLT-II were identified and logistic regression used to identify factors associated with CLND. RESULTS: Patients undergoing CLND declined from 55.9% pre-MSLT-II (n = 9725) to 19.5% post-MSLT-II (n = 9419) (odds ratio [OR] 0.32, 95% confidence interval [CI] 0.29-0.35). CLND was less likely in females (OR 0.83; 95% CI 0.78-0.89), older patients (vs. 18-39 yr; 40-64 yr OR 0.80, 95% CI 0.65-0.98; 65-79 yr OR 0.67, 95% CI 0.53-0.84; >80 yr OR 0.38, 95% CI 0.30-0.49), sicker patients (Deyo category ≥2 OR 0.85, 95% CI 0.73-0.99), thinner primary lesions (vs. 0.01-0.79 mm; 1.01-4.00 mm OR 1.16, 95% CI 1.01-1.33; ≥4.01 mm OR 1.31, 95% CI 1.08-1.59), patients from metro areas (Rural OR 1.31, 95% CI 1.00-1.70; Urban OR 1.15, 95% CI 1.03-1.29), and those treated at lower-volume centers (vs. lowest-volume; highest-volume OR 1.31, 95% CI 1.14-1.50; high-volume OR 1.40, 95% CI 1.24-1.57). CONCLUSIONS: MSLT-II has impacted clinical care; however, male gender, thicker lesions, rural/urban residence, younger age, fewer comorbidities, and treatment at higher-volume centers confer a greater likelihood of undergoing CLND. Further investigations should focus on whether these populations benefit from more aggressive surgical care.

US Women's Perceptions and Acceptance of New Reproductive Health Technologies.

Background: Women have faced persistent problems accessing reproductive health care. New applications of health technologies to reproductive health, specifically online fertility specialist consultations and reproductive hormone self-collection tests (SCTs), present unique opportunities to overcome these issues. This article uses the technology acceptance model to examine factors that influence women's intentions to use these new reproductive health technologies. Materials and Methods: Participants (n = 327 US women) completed an online survey assessing perceptions related to both of these reproductive health technologies, including usefulness, ease of use, risk, trust, subjective norms, and personal responsibility, to learn about fertility. Results: Participants indicated high perceptions of usefulness, ease of use, and trust, as well as low perceptions of risk and subjective norms for both online fertility consultations (OFCs) and reproductive hormone SCTs. Women indicated low perceptions of responsibility to use OFCs, but high perceptions of responsibility to use reproductive hormone SCTs. Structural equation modeling indicated that intentions to use OFCs were predicted by usefulness, subjective norms, and responsibility; intentions to use reproductive hormone SCTs were predicted by usefulness, ease of use, subjective norms, and responsibility. Conclusions: Fertility specialist consultations and reproductive hormone testing can provide women with essential fertility information that facilitates informed reproductive decisions; however, these services have historically been difficult to access. Widespread uptake of new reproductive health technologies could promote positive advances in women's reproductive health outcomes.

Implant-sparing Mastectomy: An Alternative for Women Undergoing Mastectomy With Retropectoral Implants.

INTRODUCTION: Implant-sparing mastectomy (ISM) is a skin-sparing mastectomy that preserves a retropectoral implant and potentially eliminates the need for tissue expansion or complex reconstruction. This study aimed to determine oncologic and surgical outcomes and reconstructive patterns in patients undergoing ISM. PATIENTS AND METHODS: A single-institution, retrospective review of patients undergoing ISM from 2006 to 2018 was performed. Patient/tumor characteristics, stage, adjuvant therapy use, 90-day complication rates, reconstruction type, and disease recurrence were collected. RESULTS: A total of 121 ISMs in 73 women were performed. Seventy (57.9%) ISMs were for breast cancer (BC) treatment and 51 (42.1%) for prophylaxis. Among BC cases, 72.3% were cT1/cT2 and 73.8% were cN0; 72.3% received systemic therapy and 33.8% received radiation therapy. There were 3 deaths owing to BC at the median follow-up of 35 months. Among 5 recurrences, only 1 was local. There was no BC identified after prophylactic ISM. Total 90-day complication rate per ISM was 15.7%. Rates were 0.8% for both seroma and wound infection, 2.5% for wound dehiscence, 3.3% for hematoma, and 8.2% for skin necrosis. The majority (72.6%) of patients required only implant exchange for reconstruction. Overall use of autologous reconstruction was low (12.3%); 77.8% of flaps were performed in patients receiving radiation therapy. CONCLUSION: ISM is a unique approach for patients pursuing mastectomy for BC treatment or prevention with equivalent oncologic outcomes and complication rates to mastectomy with reconstruction. Reconstruction for the majority was markedly simplified by elimination of tissue expansion while maintaining a low rate of flap reconstruction.

Vaccine Therapies for Breast Cancer.

Vaccines can be a cost effective preventive measure for both primary prevention of disease and prevention of disease recurrence. Several vaccines targeting breast cancer oncodrivers are currently being tested in clinical trials. Whereas clinical response rates to breast cancer vaccines have been modest despite the induction of strong antitumor T cell responses, it is through these approaches that valuable insight and knowledge have been gained about tumor immunology. With the emergence of new immunotherapies, there is renewed excitement for effective breast cancer vaccine development.

Concordance of Fingerstick and Venipuncture Sampling for Fertility Hormones.

BACKGROUND: Minimally invasive fingerstick sampling allows testing of reproductive hormone levels at home, providing women with increased access to tests that can screen for conditions such as polycystic ovarian syndrome, primary ovarian insufficiency, and pituitary and thyroid dysfunction. METHOD: We present a measurement procedure comparison study of matched venipuncture and fingerstick samples from 130 women aged 18-40 years, tested on menstrual cycle day 3. Samples were measured for anti-müllerian hormone, estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), testosterone, thyroid-stimulating hormone (TSH), and free thyroxine (T4) levels. Samples were tested using U.S. Food and Drug Administration-cleared immunoassays, with a modified reconstitution step for fingerstick samples. EXPERIENCE: Venipuncture and fingerstick hormone values were concordant and linear across all assay ranges. There was no evidence of systematic bias across the assay ranges, and bias measures were below recommended guidelines. The correlation between venipuncture and fingerstick was between 0.99 and 1.0 for each hormone. Each assay displayed a high degree of precision (less than 13% coefficient of variation) and a high level of accuracy (average recovery equaled 95.5-102.3%). CONCLUSION: Venipuncture and fingerstick samples can be used interchangeably to measure anti-müllerian hormone, E2, FSH, LH, PRL, testosterone, TSH, and free T4 levels. Fingerstick sampling provides doctors and women more convenient testing options. FUNDING SOURCE: The study was sponsored by Modern Fertility.

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 chapter, we discuss the current recommendations as well as the topics of debate in the surgical management of melanoma.

A comparison of testosterone and cortisol levels between gay fathers and non-fathers: A preliminary investigation.

Humans are unique among great apes and most other mammals, in that our wide range of offspring investment behaviors includes significant paternal care and provisioning of children. Moreover, hormones play an important role in modulating male paternal investment. Despite a growing body of research on the hormonal associations with paternal care in humans, fathers who self-identify as gay have not received the same level of research attention. We explore associations between hormones that are central to reproductive effort in American gay couples (n = 48 pairs, mean age 36 ±â€¯11 SD years) with and without children. Building on previous investigations of paternal investment, we focus on testosterone and cortisol given their primary roles in the behavioral and metabolic aspects of male reproductive effort. We provide preliminary evidence that gay fathers have lower cortisol levels compared to gay non-fathers. Cortisol and testosterone also positively co-varied in all couples, independent of potential covariates. We did not find evidence for differences in testosterone levels between gay fathers and non-fathers, although sample sizes were limited. Based on this preliminary evidence, we suggest that psychosocial stress among gay fathers may differ compared to gay couples without children, or that the stress response in gay fathers is mitigated in some way compared to non-fathers. These data underscore the importance of human paternal care diversity and the value of inclusivity in human evolutionary behavior research.

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

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.

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

BACKGROUND: 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. METHODS: Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data for 2000 through 2010, the authors examined the relationship between patient characteristics and receipt of surgery using multivariate logistic regression. The patient cohort was restricted to patients with American Joint Committee on Cancer stage I and stage II disease and Charlson Comorbidity index of ≤2. The association between treatment (surgery or chemotherapy without surgery) and hazard of death was evaluated using Kaplan-Meier Cox proportional hazards modeling. RESULTS: The authors identified 2629 patients with pancreatic adenocarcinoma who underwent either surgery (pancreatectomy) or chemotherapy without surgery. Younger patient age and smaller tumor size were found to be significantly associated with receipt of surgery. For the overall cohort, the median survival rate was significantly longer for those patients treated with surgery compared with those who received chemotherapy (15 months vs 10 months). However, the absolute survival benefit attenuated as the cohort became older. CONCLUSIONS: The survival benefit associated with surgical resection compared with chemotherapy was very small for certain subgroups of patients (those aged ≥80 years and those with lymph node metastases). The results of the current study indicate that although surgery is associated with a survival benefit in the elderly, chemotherapy should be considered as a legitimate therapeutic alternative. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:3378-3385. © 2016 American Cancer Society.

Completion Lymph Node Dissection or Observation for Melanoma Sentinel Lymph Node Metastases: A Decision Analysis.

BACKGROUND: Long-term, randomized trial results comparing completion lymph node dissection (CLND) with observation for patients with sentinel lymph node (SLN) metastases are not available. Our goal was to determine whether melanoma patients with SLN metastases should undergo CLND. METHODS: We developed a Markov model to simulate the prognosis of hypothetical cohorts of patients with SLN metastases who underwent either immediate CLND or observation with delayed CLND if macroscopic disease developed. Model parameters were derived from published studies and included the likelihood of non-SLN metastases, risk of dying from melanoma, CLND complication rates, and health-related quality-of-life weights. Outcomes included 5-year overall survival (OS), life expectancy (LE), and quality-adjusted life expectancy (QALE). RESULTS: The projected 5-year OS for 50-year-old patients with SLN metastases who underwent immediate CLND was 67.2 % compared with 63.1 % for the observation group. The LE gained by undergoing immediate CLND ranged from 2.19 years for patients aged 30 to 0.64 years for patients aged 70 years. The QALE gained by undergoing immediate CLND ranged from 1.39 quality-adjusted life years for patients aged 30 to 0.36 for patients aged 70 years. In sensitivity analysis over a clinically plausible range of values for each input parameter, immediate CLND was no longer beneficial when the rate of long-term complications increased and the quality-of-life weight for long-term complications decreased. CONCLUSIONS: Immediate CLND following positive SLN biopsy was associated with OS and QALE gains compared with observation and delayed CLND for those who develop clinically apparent LN metastases.

Lymph Node Evaluation for Pancreatic Adenocarcinoma and Its Value as a Quality Metric.

BACKGROUND: Adequate lymph node evaluation (LNE) is recommended for surgically treated pancreatic adenocarcinoma because studies have shown an association between improved survival and adequate LNE. This study aimed to understand the mechanism of this association and determine whether LNE is a valuable quality metric. METHODS: Using the linked Surveillance Epidemiology End Results Medicare database, we identified patients with surgically treated pancreatic adenocarcinoma from 2000 to 2010. Adequate LNE was defined as evaluation of ≥15 nodes. Survival was determined using Kaplan-Meier and Cox proportional hazards. RESULTS: We identified 2629 patients who underwent resection for pancreatic adenocarcinoma. Overall, 33 % had adequate LNE. Adequate LNE was significantly associated with receipt of postoperative chemotherapy. A significant decrease in hazard of death was associated with adequate LNE (HR 0.86, p < 0.05). Receipt of postoperative chemotherapy was also significantly associated with decreased hazard of death (HR 0.77, p < 0.05). On unadjusted analysis, the survival benefit associated with adequate LNE was lost when stratified by receipt of postoperative chemotherapy. CONCLUSION: The survival benefit associated with LNE is in part derived from the fact that patients who receive adequate LNE are also more likely to receive chemotherapy. Thus, the use of lymph node counts has limitations as a quality metric.

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.

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.

Perceptions of Contralateral Breast Cancer Risk: A Prospective, Longitudinal Study.

PURPOSE: An increasing proportion of breast cancer patients undergo contralateral prophylactic mastectomy (CPM) to reduce their risk of contralateral breast cancer (CBC). Our goal was to evaluate CBC risk perception changes over time among breast cancer patients. METHODS: We conducted a prospective, longitudinal study of women with newly diagnosed unilateral breast cancer. Patients completed a survey before and approximately 2 years after treatment. Survey questions used open-ended responses or 5-point Likert scale scoring (e.g., 5 = very likely, 1 = not at all likely). RESULTS: A total of 74 women completed the presurgical treatment survey, and 43 completed the postsurgical treatment survey. Baseline characteristics were not significantly different between responders and nonresponders of the follow-up survey. The mean estimated 10-year risk of CBC was 35.7 % on the presurgical treatment survey and 13.8 % on the postsurgical treatment survey (p < 0.001). The perceived risks of developing cancer in the same breast and elsewhere in the body significantly decreased between surveys. Both CPM and non-CPM (breast-conserving surgery or unilateral mastectomy) patients' perceived risk of CBC significantly decreased from pre- to postsurgical treatment surveys. Compared with non-CPM patients, CPM patients had a significantly lower perceived 10-year risk of CBC (5.8 vs. 17.3 %, p = 0.046) on postsurgical treatment surveys. CONCLUSIONS: The perceived risk of CBC significantly attenuated over time for both CPM and non-CPM patients. These data emphasize the importance of early physician counseling and improvement in patient education to provide women with accurate risk information before they make surgical treatment decisions.