Germline PALB2 Variants and PARP Inhibitors in Endometrial Cancer.

PARP inhibitors are orally administered antineoplastic agents that affect the homologous recombination (HR) repair pathway, and are approved by the FDA for the treatment of ovarian, breast, pancreatic, and prostate cancers. This report presents a case of recurrent endometrial carcinoma occurring in a woman with a germline pathogenic PALB2 whole-exon deletion. This uncommon finding in a patient with endometrial carcinoma provided the opportunity to use a management strategy of PARP inhibition with olaparib, resulting in a prolonged response to treatment; however, disease progression eventually occurred. Further studies are required to elucidate the mechanisms underlying resistance to PARP inhibition, and the potential future treatment options in this setting. Current recommendations for risk management of female carriers of PALB2 variants focus on breast and ovarian cancer risk. This case raises the additional question of a potential role for risk-reducing hysterectomy in female carriers of PALB2 variants.

Using hospital registries in Australia to extend data availability on vulval cancer treatment and survival.

BACKGROUND: The value of hospital registries for describing treatment and survival outcomes for vulval cancer was investigated. Hospital registry data from four major public hospitals in 1984-2016 were used because population-based data lacked required treatment and outcomes data. Unlike population registries, the hospital registries had recorded FIGO stage, grade and treatment. METHODS: Unadjusted and adjusted disease-specific survival and multiple logistic regression were used. Disease-specific survivals were explored using Kaplan-Meier product-limit estimates. Hazards ratios (HRs) were obtained from proportional hazards regression for 1984-1999 and 2000-2016. Repeat analyses were undertaken using competing risk regression. RESULTS: Five-year disease-specific survival was 70%, broadly equivalent to the five-year relative survivals reported for Australia overall (70%), the United Kingdom (70%), USA (72%), Holland (70%), and Germany (Munich) (68%). Unadjusted five-year survival tended to be lower for cancers diagnosed in 2000-2016 than 1984-1999, consistent with survival trends reported for the USA and Canada, but higher for 2000-2016 than 1984-1999 after adjusting for stage and other covariates, although differences were small and did not approach statistical significance (p ≥ 0.40). Surgery was provided as part of the primary course of treatment for 94% of patients and radiotherapy for 26%, whereas chemotherapy was provided for only 6%. Less extensive surgical procedures applied in 2000-2016 than 1984-1999 and the use of chemotherapy increased over these periods. Surgery was more common for early FIGO stages, and radiotherapy for later stages with a peak for stage III. Differences in treatment by surgery and radiotherapy were not found by geographic measures of remoteness and socioeconomic status in adjusted analyses, suggesting equity in service delivery. CONCLUSIONS: The data illustrate the complementary value of hospital-registry data to population-registry data for informing local providers and health administrations of trends in management and outcomes, in this instance for a comparatively rare cancer that is under-represented in trials and under-reported in national statistics. Hospital registries can fill an evidence gap when clinical data are lacking in population-based registries.