A Not So Perfect Score: Factors Associated with the Rate of Straight Line Scoring in Oncology Training Programs.

Straight line scoring (SLS), defined as trainee assessments with the same score for all evaluation items, is statistically improbable and potentially indicates inaccurate assessment. Factors contributing to higher SLS rates are unknown, and knowledge of SLS prevalence within oncologic training is lacking. SLS frequency was measured for evaluations from all Accreditation Council for Graduate Medical Education (ACGME)-accredited programs at a single cancer care institution between 2014 and 2018. SLS prevalence was estimated using hierarchical linear models (HLM) that considered characteristics of evaluator, trainee, and evaluation potentially related to SLS. Results were compared with national SLS rates. Six thousand one hundred sixty evaluations were included from 476 evaluators. Overall prevalence of SLS was 12.1% (95% CI 4.5-28.8). Residents (vs fellows) were less likely to have SLS evaluations (OR 0.5, 95% CI 0.4-0.8), though for all trainees increasing training year corresponded with increasing SLS frequency (OR 1.5, 95% CI 1.3-1.7). SLS was more common in procedural specialties compared with medical specialties (OR 2.1, 95% CI 1.1-3.8). Formative evaluations had lower SLS rates (OR 0.6, 95% CI 0.5-0.9) than summative evaluations, while milestone-based evaluations had higher rates than those that were not milestone-based (OR 1.5, 95% CI 1.03-2.2). Features of evaluators, such as subspecialty within oncology, and of trainees, such as seniority or trainee type, were related to SLS. Summative intent and milestone-based evaluations were more likely to be straight line scored. Specific evaluation scenarios at higher risk of SLS should be further examined.

Immunotherapy combined with high- and low-dose radiation to all sites leads to complete clearance of disease in a patient with metastatic vaginal melanoma.

A 73-year-old woman with metastatic vaginal mucosal melanoma that had progressed on ipilimumab and nivolumab experienced clinical and radiographic complete response to dual checkpoint inhibitor immunotherapy given in combination with high-dose plus low-dose radiation. General characteristics and treatment options in this disease are highlighted.

Correlation of surgeon radiology assessment with laparoscopic disease site scoring in patients with advanced ovarian cancer.

BACKGROUND: Radiographic triage measures in patients with new advanced ovarian cancer have yielded inconsistent results. OBJECTIVE: To determine the correlation between surgeon radiology assessment and laparoscopic scoring by disease sites in patients with newly diagnosed advanced stage ovarian cancer. METHODS: Fourteen gynecologic oncology surgeons from a single institution performed a blinded review of pre-operative contrast-enhanced CT imaging from patients with advanced stage ovarian cancer. Each of the patients had also undergone laparoscopic scoring assessment, between April 2013 and December 2017, to determine primary resectability using the validated Fagotti scoring method, and assigned a predictive index value score. Surgeons were asked to provide expected predictive index value scores based on their blinded review of the antecedent CT imaging. Linear mixed models were conducted to calculate the correlation between radiologic and laparoscopic score for surgeons individually, and as a group. Once the model was fit, the inter-class correlation and 95% CI were calculated. RESULTS: Radiology review was performed on 20 patients with advanced stage ovarian cancer who underwent laparoscopic scoring assessment. Surgeon faculty rank included assistant professor (n=5), associate professor (p=4), and professor (n=5). The kappa inter-rater agreement was -0.017 (95% CI -0.023 to -0.005), indicating low inter-rater agreement between radiology review and actual laparoscopic score. The inter-class correlation in this model was 0.06 (0.02-0.21), indicating that surgeons do not score the same across all the images. When using a clinical cut-off point for the predictive index value of 8, the probability of agreement between radiology and actual laparoscopic score was 0.56 (95% CI 0.49 to 0.73). Examination of disease site sub-scales showed that the probability of agreement was as follows: peritoneum 0.57 (95% CI 0.51 to 0.62), diaphragm 0.54 (95% CI 0.48 to 0.60), mesentery 0.51 (95% CI 0.45 to 0.57), omentum 0.61 (95% CI 0.55 to 0.67), bowel 0.54 (95% CI 0.44 to 0.64), stomach 0.71 (95% CI 0.65 to 0.76), and liver 0.36 (95% CI 0.31 to 0.42). The number of laparoscopic scoring cases, tumor reductive surgery cases, or faculty rank was not significantly associated with overall or sub-scale agreement. CONCLUSIONS: Surgeon radiology review did not correlate highly with actual laparoscopic scoring assessment findings in patients with advanced stage ovarian cancer. Our study highlights the limited accuracy of surgeon radiographic assessment to determine resectability.

Movement of Poly-ADP Ribose (PARP) Inhibition into Frontline Treatment of Ovarian Cancer.

The use of poly (ADP-ribose) polymerase (PARP) inhibitors in the front-line management of advanced ovarian cancer has recently emerged as an exciting strategy with the potential to improve outcomes for patients with advanced ovarian cancer. In this article, we review the results of four recently published Phase III randomised controlled trials evaluating the use of PARP inhibitors in the primary treatment of ovarian cancer (SOLO1, PRIMA, PAOLA-1, and VELIA). Collectively, the studies suggest that PARP maintenance in the upfront setting is most beneficial among patients with BRCA-associated ovarian cancers (hazard ratios range from 0.31 to 0.44), followed by patients with tumours that harbour homologous recombination deficiencies (hazard ratios range from 0.33 to 0.57). All three studies that included an all-comer population were able to demonstrate benefit of PARP inhibitors, regardless of biomarker status. The FDA has approved olaparib for front-line maintenance therapy among patients with BRCA-associated ovarian cancers, and niraparib for all patients, regardless of biomarker status. In determining which patients should be offered front-line maintenance PARP inhibitors, and which agent to use, there are multiple factors to consider, including FDA indication, dosing preference, toxicity, risks versus benefits for each patient population, and cost. There are ongoing studies further exploring the front-line use of PARP inhibitors, including the potential downstream effects of PARP-inhibitor resistance in the recurrent setting, combining PARP-inhibitors with other anti-angiogenic drugs, immunotherapeutic agents, and inhibitors of pathways implicated in PARP inhibitor resistance.

ITLN1 modulates invasive potential and metabolic reprogramming of ovarian cancer cells in omental microenvironment.

Advanced ovarian cancer usually spreads to the omentum. However, the omental cell-derived molecular determinants modulating its progression have not been thoroughly characterized. Here, we show that circulating ITLN1 has prognostic significance in patients with advanced ovarian cancer. Further studies demonstrate that ITLN1 suppresses lactotransferrin's effect on ovarian cancer cell invasion potential and proliferation by decreasing MMP1 expression and inducing a metabolic shift in metastatic ovarian cancer cells. Additionally, ovarian cancer-bearing mice treated with ITLN1 demonstrate marked decrease in tumor growth rates. These data suggest that downregulation of mesothelial cell-derived ITLN1 in the omental tumor microenvironment facilitates ovarian cancer progression.

Adjuvant therapy for grade 3, deeply invasive endometrioid adenocarcinoma of the uterus.

BACKGROUND: Patients with grade 3, deeply invasive endometrioid adenocarcinoma are typically managed with primary surgery. The role and type of adjuvant therapy used is controversial. We sought to evaluate the role of adjuvant radiation and/or chemotherapy in women with deeply invasive grade 3 endometrioid tumors. METHODS: A multi-center retrospective chart review was performed at three large medical institutions in the United States. Patients with grade 3 endometrioid adenocarcinoma invading >50% of the myometrium were included. Medical records were queried to evaluate whether lymph node assessment was performed, the status of the lymph nodes, adjuvant treatment strategy used, and dates of death or recurrence. RESULTS: Between 1984 and 2013, 257 patients were identified with a median follow-up of 3.08 years. Most patients (84.7%) had evaluation of pelvic and/or para-aortic lymph nodes and 43% had positive lymph nodes. For node negative patients, there was no difference in overall survival (OS) between those who received adjuvant pelvic radiation +/- vaginal brachytherapy (n=52) vs brachytherapy alone (n=46) (5-year probabilities were 0.73 vs 0.70, P=0.729). Among patients with positive lymph nodes (n=92), the adjuvant treatment strategy utilized impacted OS, with women undergoing a combination of chemotherapy and external beam radiation having the best outcomes (P=0.003). CONCLUSIONS: Among women with grade 3, deeply invasive endometrioid adenocarcinoma, vaginal cuff brachytherapy alone resulted in similar survival when compared with pelvic radiation in node negative patients. The combination of chemotherapy with external beam radiation was associated with improved OS for women with positive nodes.

Breast-Specific Sensuality and Sexual Function in Cancer Survivorship: Does Surgical Modality Matter?

PURPOSE: More early-staged breast cancer patients are choosing mastectomy. No studies have addressed breast-specific sensuality (BSS), defined as the breast's role during intimacy. We explored BSS among women undergoing lumpectomy (L), mastectomy alone (M), or with reconstruction (MR) and analyzed the association of surgical modality with sexual function. METHODS: Women undergoing breast cancer surgery between 2000 and 2013 were eligible for survey using investigator-generated questions and the Female Sexual Function Index (FSFI). Demographic and surgical data were collected by chart review. The Kruskal-Wallis test was used to analyze FSFI scores, and χ 2 or Fisher's exact tests were used for categorical data. RESULTS: Of 453 invited participants, 268 (59%) completed the survey. Of these, 69.4, 22.4, and 8.2% underwent L, MR, or M, respectively. The importance of the breast/chest wall during intimacy declined significantly regardless of surgical modality (L 83-74%, p = 0.0006; M 95-47%, p = 0.003; MR 93-77%, p = 0.002). No difference in sexual function was found between L, MR, and M (median FSFI score 28.2, 27.5, 25.9, respectively; p = 1.0). Comparing L versus MR, higher FSFI scores resulted with appearance satisfaction (29.0 vs. 22.6 p = 0.002) and preserved BSS as pleasurable breast caress (28.8 vs. 26.5, p = 0.04) and the breast as part of intimacy (28.8 vs. 24.8, p = 0.1). CONCLUSIONS: Breast cancer surgery is associated with lowered BSS. However, BSS and appearance satisfaction scores are better for L and appear to correlate with improved sexual function postoperatively. These data may guide surgical counseling and contribute to survivorship outcomes.

Endometrial Cancers With Activating KRas Mutations Have Activated Estrogen Signaling and Paradoxical Response to MEK Inhibition.

OBJECTIVES: The aims of this study were to determine if activating KRas mutation alters estrogen signaling in endometrial cancer (EC) and to explore the potential therapeutic impact of these alterations. METHODS: The Cancer Genome Atlas was queried for changes in estrogen-regulated genes in EC based on KRas mutation status. In vitro studies were conducted to evaluate estrogen receptor α (ERα) phosphorylation changes and related kinase changes in KRas mutant EC cells. The resulting effect on response to MEK inhibition, using trametinib, was evaluated. Immunohistochemistry was performed on KRas mutant and wild-type EC tumors to test estrogen signaling differences. RESULTS: KRas mutant tumors in The Cancer Genome Atlas showed decreased progesterone receptor expression (P = 0.047). Protein analysis in KRas mutant EC cells also showed decreased expression of ERα (P < 0.001) and progesterone receptor (P = 0.001). Although total ERα is decreased in KRas mutant cells, phospho-ERα S118 was increased compared with wild type. Treatment with trametinib in KRas mutant cells increased phospho-ERα S167 and increased expression of estrogen-regulated genes. While MEK inhibition blocked estradiol-stimulated phosphorylation of ERK1/2 and p90RSK in wild-type cells, phospho-ERK1/2 and phospho-p90RSK were substantially increased in KRas mutants. KRas mutant EC tumor specimens showed similar changes, with increased phospho-ERα S118 and phospho-ERα S167 compared with wild-type EC tumors. CONCLUSIONS: MEK inhibition in KRas mutant cells results in activation of ER signaling and prevents the abrogation of signaling through ERK1/2 and p90RSK that is achieved in KRas wild-type EC cells. Combination therapy with MEK inhibition plus antiestrogen therapy may be necessary to improve response rates in patients with KRas mutant EC.

Addressing the Role of Obesity in Endometrial Cancer Risk, Prevention, and Treatment.

In sharp contrast to many other cancer types, the incidence and mortality of endometrial cancer continue to grow. This unfortunate trend is, in no small part, a result of the worldwide obesity epidemic. More than half of endometrial cancers are currently attributable to obesity, which is recognized as an independent risk factor for this disease. In this review, we identify the molecular mechanisms by which obesity and adipose tissue contribute to the pathogenesis of endometrial cancer. We further discuss the impact of obesity on the clinical management of the disease and examine the development of rational behavioral and pharmaceutical interventions aimed at reducing endometrial cancer risk, improving cancer outcomes, and preserving fertility in an increasingly younger population of patients with endometrial cancer.

Influential Forces in Breast Cancer Surgical Decision Making and the Impact on Body Image and Sexual Function.

BACKGROUND: Shared decision making with one's partner and body image satisfaction may affect surgical choices of breast cancer patients. This study analyzed whether partner opinion was associated with choice of operation and whether comfort level with one's partner was altered postoperatively. METHODS: A prospective anonymous survey was administered to breast cancer patients who underwent breast surgery between 2000 and 2014. Categorical variables were compared by χ (2) or Fisher's exact test. RESULTS: Women who elected to undergo mastectomy with reconstruction (MR) placed greater emphasis on their own decision making than on input from their partner, surgeon, or others (56.5 vs. 8.3 vs. 23.2 vs. 12, respectively), whereas those who chose lumpectomy (L) placed similar weight on surgeon input and self-input (44.2 vs. 42.7 %). Only 7.5 % of all patients identified their partner as the greatest influence on their surgical choice. Preoperatively, the L group was the most comfortable with their partner seeing their chest (91.9 % L vs. 83.9 % MR vs. 75.9 % mastectomy alone (M); p = 0.01), and postoperatively, the comfort levels for all were remarkably decreased. Furthermore, if a patient was a candidate for L but chose MR, the role her chest played in intimacy dropped more compared with those who chose L (83.8 % L vs. 91.7 % MR; p = 0.3 preoperatively to 65.1 % L vs. 42.9 % MR; p = 0.01 postoperatively). CONCLUSIONS: When making surgical decisions, most patients indicate that they value their own opinion over that of others. Mastectomy, regardless of reconstruction, leads to a significant reduction in comfort with one's partner postoperatively compared with lumpectomy. This information may be helpful in counseling couples at the time of consultation for breast cancer treatment.

Hereditary breast cancer: an update on risk assessment and genetic testing in 2015.

The last 5 years have brought significant innovation and advancement in the genetics of breast cancer. This clinical opinion aims to summarize and update current approaches to the care of women at risk for a hereditary predisposition to breast cancer. Implications of the BRCA mutation and several other hereditary syndromes will be discussed. Risk assessment and criteria for referral to cancer genetic professionals as well as high-risk screening and prophylactic options will be reviewed. Finally, the newly available genetic cancer panels and implications of mutations in some of these lesser known genes will be discussed. As the field of cancer genetics continues to evolve, the education of medical students, residents, and faculty will be paramount to identify appropriate candidates for genetic counseling and testing in conjunction with cancer genetic professionals.

Benign breast disorders.

Full understanding of benign breast disease should enable the obstetrician-gynecologist to appropriately evaluate symptoms, distinguish between benign and malignant processes, determine which benign breast lesions require surgical management, and identify patients who are at increased risk of developing breast cancer. This article reviews nipple discharge, breast pain, palpable breast masses, adolescent breast disorders, inflammatory lesions (including mastitis and breast abscesses), and benign breast abnormality detected on imaging and biopsy. Each topic provides a review of the clinical presentation, a discussion of the appropriate workup, and a further description of specific etiology within each category.