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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. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the safety and primary technical success rate of gastric decompression via percutaneous transabdominal gastrostomy (PTAG) or percutaneous transesophageal gastric (PTEG) catheter placement for management of malignant bowel obstruction (MBO). A secondary purpose was to evaluate the safety and success rate for PTAG catheter placement in patients with both MBO and ascites. Methods: A single-institution retrospective review of 385 patients who underwent attempted decompression gastric catheter placement from March 2013 to August 2018 was performed. Medical records and imaging studies were reviewed. A subgroup of patients with concomitant MBO and ascites were identified. The primary outcome measures were procedural technical success and procedural complications. Results: 394 decompression gastrostomy catheters were attempted from 2013 to 2018, n = 353 PTAG and n = 41 PTEG. The success rate was 95.5% (n = 337 of 353) for PTAG and 97.6% (n = 40 of 41) for PTEG. There were 63 total complications involving 47 (13.9%) patients following PTAG and 13 total complications involving 9 (22.5%) patients following PTEG, P = 0.16. For the subgroup of patients with MBO and ascites, the success rate was 94.8% (n = 182 of 192 patients), and there were 20 complications involving 17 (12.9%) of 132 patients. Conclusion: Gastric decompression for patients with MBO via PTAG or PTEG catheter placement is associated with high success rates and low complications. [ABSTRACT FROM AUTHOR]

Summary: Background Treatment of recurrent, unresectable granulosa cell tumor (GCT) of the ovary can be challenging. Given the rarity of the tumor, alternative therapies have been difficult to evaluate in large prospective clinical trials. Currently, to our knowledge, there are no reports of the use of immune checkpoint inhibitors in GCT patients. Here, we present a case series of GCT patients treated with pembrolizumab who were enrolled in a phase II basket trial in advanced, rare solid tumors (ClinicalTrials.gov: NCT02721732). Cases We identified 5 patients with recurrent GCT (4 adult and 1 juvenile type); they had an extensive history of systemic therapy at study enrollment (range, 3–10), with most regimens resulting in less than 12 months of disease control. Pembrolizumab was administered in these patients, as per trial protocol. Although there were no objective responses according to the irRECIST guidelines, 2 patients with adult-type GCT experienced disease control for ≥ 12 months (565 and 453 days). In one, pembrolizumab represented the longest duration of disease control compared to prior lines of systemic therapy (565 days vs. 13 months). In the other, pembrolizumab was the second longest systemic therapy associated with disease control (453 days vs. 22 months) compared to prior lines of therapy. In this patient, pembrolizumab was discontinued following withdrawal of consent. PD-L1 expression was not observed in any baseline tumor samples. Pembrolizumab was well tolerated, with no grade 3 or 4 treatment-related adverse events. Conclusions Although our results do not support the routine use of pembrolizumab monotherapy in unselected GCT patients, some patients with adult-type GCT may derive a clinical benefit, with a low risk of toxicity. Future studies should investigate the role of immunotherapy and predictors of clinical benefit in this patient population. [ABSTRACT FROM AUTHOR]

Vaginal and vulvar squamous cell carcinoma (SCC) are rare tumors that can be challenging to treat in the recurrent or metastatic setting. We present a case series of patients with vaginal or vulvar SCC who were treated with single-agent pembrolizumab as part of a phase II basket clinical trial to evaluate efficacy and safety. Two cases of recurrent and metastatic vaginal SCC, with multiple prior lines of systemic chemotherapy and radiation, received pembrolizumab. One patient had significant reduction (81%) in target tumor lesions prior to treatment discontinuation at cycle 10 following confirmed progression of disease with new metastatic lesions (stable disease by irRECIST criteria). In contrast, the other patient with vaginal SCC discontinued treatment after cycle 3 due to disease progression. Both patients had PD-L1 positive vaginal tumors and tolerated treatment well. One case of recurrent vulvar SCC with multiple surgical resections and prior progression on systemic carboplatin had a 30% reduction in her target tumor lesions following pembrolizumab treatment with a PD-L1 positive tumor. Treatment was discontinued for grade 3 mucositis after cycle 5. Pembrolizumab may provide some clinical benefit to some patients with vaginal or vulvar SCC and is overall safe to utilize in this population. Future studies are needed to evaluate the efficacy of pembrolizumab in these rare tumor types and to identify predictive biomarkers of response. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy has become a powerful treatment option for several solid tumor types. The presence of tumor-infiltrating lymphocytes (TIL) is correlated with better prognosis in ovarian cancer, pointing at the possibility to benefit from harnessing their anti-tumor activity. This preclinical study explores the feasibility of adoptive cell therapy (ACT) with TIL using an improved culture method. Methods: TIL from high-grade serous ovarian cancer were cultured using a combination of IL-2 with agonistic antibodies targeting 4-1BB and CD3. The cells were phenotyped using flow cytometry in the fresh tissue and after expansion. Tumor reactivity was assessed against HLA-matched ovarian cancer cell lines via IFN-γ ELISPOT. Results: Ovarian cancer is highly infiltrated with CD8+ TIL that are preferentially and robustly expanded with the addition of the agonistic antibodies. With a 95% success rate, the TIL are grown to ≥ 100 × 106 cells in 2–3 weeks without over differentiation. In addition, the CD8+ TIL grown with this method showed HLA-restricted tumor recognition. Conclusions: These results indicate the viability of TIL ACT for refractory ovarian cancer by allowing for the large expansion of anti-tumor TIL in a short time and consistent manner. [ABSTRACT FROM AUTHOR]

Opinion Statement: Immune-targeted therapies have demonstrated durable responses in many tumor types with limited treatment options and poor overall prognosis. This has led to enthusiasm for expanding such therapies to other tumor types including gynecologic malignancies. The use of immunotherapy in gynecologic malignancies is in the early stages and is an active area of ongoing clinical research. Both cancer vaccines and immune checkpoint inhibitor therapy continue to be extensively studied in gynecologic malignancies. Immune checkpoint inhibitors, in particular, hold promising potential in specific subsets of endometrial cancer that express microsatellite instability. The key to successful treatment with immunotherapy involves identification of the subgroup of patients that will derive benefit. The number of ongoing trials in cervical, ovarian, and endometrial cancer will help to recognize these patients and make treatment more directed. Additionally, a number of studies are combining immunotherapy with standard treatment options and will help to determine combinations that will enhance responses to standard therapy. Overall, there is much enthusiasm for immunotherapy approaches in gynecologic malignancies. However, the emerging data shows that with the exception of microsatellite unstable tumors, the use of single-agent immune checkpoint inhibitors is associated with response rates of 10-15%. More effective and likely combinatorial approaches are needed and will be informed by the findings of ongoing trials. [ABSTRACT FROM AUTHOR]

Objective: To investigate the prognostic and biologic significance of immune-related gene expression in high grade serous ovarian cancer (HGSOC). Methods: Gene expression dependent survival analyses for a panel of immune related genes were evaluated in HGSOC utilizing The Cancer Genome Atlas (TCGA). Prognostic value of LCK was validated using IHC in an independent set of 72 HGSOC. Prognostic performance of LCK was compared to cytolytic score (CYT) using RNAseq across multiple tumor types. Differentially expressed genes in LCK high samples and gene ontology enrichment were analyzed. Results: High pre-treatment LCK mRNA expression was found to be a strong predictor of survival in a set of 535 ovarian cancers. Patients with high LCK mRNA expression had a longer median progression free survival (PFS) of 29.4 months compared to 16.9 months in those without LCK high expression (p = 0.003), and longer median overall survival (OS) of 95.1 months versus 44.5 months (p = 0.001), which was confirmed in an independent cohort by IHC (p = 0.04). LCK expression was compared to CYT across tumor types available in the TCGA and was a significant predictor of prognosis in HGSOC where CYT was not predictive. Unexpectedly, LCK high samples also were enriched in numerous immunoglobulin-related and other B cell transcripts. Conclusions: LCK is a better prognostic factor than CYT in ovarian cancer. In HGSOC, LCK high samples were characterized by higher expression of immunoglobulin and B-cell related genes suggesting that a cooperative interaction between tumor infiltrating T and B cells may correlate with better survival in this disease. [ABSTRACT FROM AUTHOR]

Both the estrogen receptor (ER) and the progesterone receptor (PR) have two subtypes: ER-α and β, and PR-A and -B, respectively. These subtypes differ in function and expression, and recent reports have correlated changes in the normal proportions of these isoforms with neoplastic states. We investigated ER and PR isoform expression in normal pre- and post-menopausal endometrium, well-differentiated endometrial adenocarcinoma, and poorly differentiated malignant mixed mullerian tumors (MMMTs). Semi-quantitative RT–PCR and immunoblotting were used to measure receptor mRNA and protein expression. Estrogen receptor-α/β mRNA ratios were significantly higher in postmenopausal (27.3) compared to premenopausal endometrium (4.9) mainly as a result of lower ER-β expression in the former. Compared to age-matched postmenopausal controls, the ER-α/β ratio was reduced in both grade I adenocarcinoma and MMMT specimens (3.3 and 6.8, respectively), due to a selective loss of ER-α. The relative abundance of PR-A and PR-B mRNA remained unchanged between all tissue subtypes. Total PR protein, however, was significantly reduced in MMMTs compared to all other groups. Thus, sex steroid receptor expression is significantly and differentially altered in well-differentiated and poorly-differentiated endometrial cancers. Both cancers exhibit decreased ER-α expression and the MMMTs also demonstrate a significant loss of PR protein. Oncogene (2001) 20, 6965–6969. [ABSTRACT FROM AUTHOR]

Platinum-based therapy is the cornerstone of ovarian cancer treatment. Development of platinum hypersensitivity can limit therapeutic options. In this brief report, we present case of successful cisplatin administration following two unsuccessful carboplatin desensitization attempts, and without the need for pre-treatment steroids. Retrospective chart review was performed. One case of recurrent primary peritoneal carcinoma previously treated with a carboplatin-based regimen, developed a platinum hypersensitivity. Two attempts at carboplatin desensitization were unsuccessful. Cisplatin was substituted and the patient achieved a complete response to therapy without further hypersensitivity. Platinum-based therapies are vital to the treatment of primary peritoneal and ovarian carcinoma. Protocols that successfully incorporate platinum agents, despite a platinum hypersensitivity, are clinically relevant. [ABSTRACT FROM AUTHOR]