Survival disparities in vulvar cancer patients in Commission on Cancer®-accredited facilities.

OBJECTIVES: To investigate survival disparities and prognostic factors in vulvar cancer by age at diagnosis. METHODS: Women who underwent surgery and were diagnosed with stage I-IV vulvar cancer from 2004 to 2014 in the National Cancer Database were eligible. Proportions were compared using Chi-Square test. Survival was evaluated using Cox analysis. RESULTS: There were 18,207 eligible women. Median age at diagnosis was 64 years, and 31% diagnosed ≥75 years old were categorized as elderly. Most vulvar cancers were diagnosed at stage I and with squamous histology. Diagnosis with higher stage or non-squamous histology was more common in elderly vs. non-elderly patients (P < 0.001). Survival was 3.5 times worse in the elderly than the non-elderly (P < 0.0001). Risk of death for each 5-year increment in age increased by 22% for non-elderly and 43% for elderly patients (P < 0.0001). The prognostic value of comorbidity score, stage, regional node assessment and histology was smaller in elderly vs. non-elderly women (each P < 0.05). Adjuvant chemoradiotherapy (CTRT) use in the elderly vs. non-elderly was rare for stage I-II disease (3% vs. 2%) and more common for stage III-IV disease (6% vs. 43%), respectively (P < 0.0001). The survival disadvantage for elderly patients persisted following no adjuvant therapy, radiotherapy or chemotherapy alone, or CTRT (P < 0.0001). In stage III-IV disease, survival was superior following CTRT vs. radiotherapy when diagnosed <75 years (HR = 0.80, 95% CI = 0.69-0.93) but not in the elderly (HR = 0.99, P > 0.05). CONCLUSIONS: Age-associated risk of death increased at different rates in vulvar cancer and was larger in elderly vs. non-elderly patients. The impact of other prognostic factors was smaller in elderly vs. non-elderly women. The survival benefit of CTRT over radiotherapy in stage III-IV did not extend to the elderly.

BiTE secretion by adoptively transferred stem-like T cells improves FRα+ ovarian cancer control.

BACKGROUND: Cancer immunotherapies can produce complete therapeutic responses, however, outcomes in ovarian cancer (OC) are modest. While adoptive T-cell transfer (ACT) has been evaluated in OC, durable effects are rare. Poor therapeutic efficacy is likely multifactorial, stemming from limited antigen recognition, insufficient tumor targeting due to a suppressive tumor microenvironment (TME), and limited intratumoral accumulation/persistence of infused T cells. Importantly, host T cells infiltrate tumors, and ACT approaches that leverage endogenous tumor-infiltrating T cells for antitumor immunity could effectively magnify therapeutic responses. METHODS: Using retroviral transduction, we have generated T cells that secrete a folate receptor alpha (FRα)-directed bispecific T-cell engager (FR-B T cells), a tumor antigen commonly overexpressed in OC and other tumor types. The antitumor activity and therapeutic efficacy of FR-B T cells was assessed using FRα+ cancer cell lines, OC patient samples, and preclinical tumor models with accompanying mechanistic studies. Different cytokine stimulation of T cells (interleukin (IL)-2+IL-7 vs IL-2+IL-15) during FR-B T cell production and the resulting impact on therapeutic outcome following ACT was also assessed. RESULTS: FR-B T cells efficiently lysed FRα+ cell lines, targeted FRα+ OC patient tumor cells, and were found to engage and activate patient T cells present in the TME through secretion of T cell engagers. Additionally, FR-B T cell therapy was effective in an immunocompetent in vivo OC model, with response duration dependent on both endogenous T cells and FR-B T cell persistence. IL-2/IL-15 preconditioning prior to ACT produced less differentiated FR-B T cells and enhanced therapeutic efficacy, with mechanistic studies revealing preferential accumulation of TCF-1+CD39-CD69- stem-like CD8+ FR B T cells in the peritoneal cavity over solid tumors. CONCLUSIONS: These findings highlight the therapeutic potential of FR-B T cells in OC and suggest FR-B T cells can persist in extratumoral spaces while actively directing antitumor immunity. As the therapeutic activity of infused T cell therapies in solid tumor indications is often limited by poor intratumoral accumulation of transferred T cells, engager-secreting T cells that can effectively leverage endogenous immunity may have distinct mechanistic advantages for enhancing therapeutic responses rates.

Fertility-sparing treatment of locally advanced vulvar squamous cell carcinoma in a young patient.

•Locally advanced vulvar cancer has been diagnosed in a young patient who desires fertility.•Treatment of vulvar cancer in young patients will need to consider future reproductive planning.•Fertility-sparing radiation techniques for treatment of vulvar cancer are effective in achieving long-term disease control.

Temperature dependence of conjugation of amyloid beta protein on the surfaces of gold colloidal nanoparticles.

The absorption spectrum of the amyloid beta 1-40 peptide (Abeta(1-40)) conjugated to gold colloidal suspension of 15, 20, 30, and 40 nm size were examined under temperature ranging from 5 to 50 degrees C. As the pH was externally altered repetitively between pH 4 and 10, Abeta(1-40)-coated 20 nm gold colloid nanoparticles exhibited a reversible color change at the entire temperature range tested in this study except for 5 +/- 0.2 degrees C. This reversible change may be due to the fact that hydrophilic Abeta(1-40) evolves between a three-dimensional network containing mainly beta-sheet and alpha-helices, and an intermediate of this process implies a reversible step reported as initiation of the fibrillogenesis in Alzheimer's disease. When other nanosize particles were investigated, Abeta(1-40)-coated 30 and 40 nm colloids exhibited the reversible color change when temperature was lowered to 18 +/- 0.2 and 6 +/- 0.2 degrees C, respectively. This specific and unique size and temperature dependence in reversible color change strongly suggests that the noncovalent intrinsic intermolecular potential formed between the nanocolloidal surface and each Abeta(1-40) monomer conjugated at the surface drives the process.

Invasive endometrial adenocarcinoma and missed abortion: A case report.

BACKGROUND: Endometrial cancer is the most common gynecologic cancer in the United States; however, reports of endometrial cancer diagnosed in the setting of intrauterine gestation are rare. CASE: We describe the case of a clinical stage IA grade 1 endometrioid endometrial adenocarcinoma diagnosed at the time of D&C performed for missed abortion in a gravida 1 para 0 female with no identifiable risk factors. Fertility-sparing treatment, with combined oral megestrol acetate and levonorgestrel intrauterine system, was used to manage this incidentally-diagnosed carcinoma with endometrial sampling every 3 months.