Stromal FAP is an independent poor prognosis marker in non-small cell lung adenocarcinoma and associated with p53 mutation.

OBJECTIVES: Fibroblasts regulate tumor growth and immune surveillance. Here, we study FAP, PDGFßR and α-SMA fibroblast markers in a well-annotated clinical cohort of non-small-cell lung cancer (NSCLC) for analyses of associations with immune cell infiltration, mutation status and survival. MATERIALS AND METHODS: A well-annotated NSCLC cohort was subjected to IHC analyses of stromal expression of FAP, PDGFßR and α-SMA and of stromal CD8 density. Fibroblast markers-related measurements were analyzed with regard to potential associations with CD8 density, cancer genetic driver mutations, survival and PD-L1 expression in the whole NSCLC cohort and in subsets of patients. RESULTS: High stromal FAP expression was identified as an independent poor prognostic marker in the whole study population (HR 1.481; 95 % CI, 1.012-2.167, p = 0.023) and in the histological subset of adenocarcinoma (HR 1.720; 95 % CI, 1.126-2.627, p = 0.012). Among patients with adenocarcinoma, a particularly strong association of FAP with poor survival was detected in patients with low stromal CD8 infiltration, and in other subpopulations identified by specific clinical characteristics; elderly patients, females, non-smokers and patients with normal ECOG performance status. α-SMA expression was negatively associated with CD8 infiltration in non-smokers, but none of the fibroblast markers expression was associated with CD8 density in the whole study population. Significant associations were detected between presence of p53 mutations and high α-SMA (p = 0.003) and FAP expression (p < 0.001). CONCLUSION: The study identifies FAP intensity as a candidate independent NSCLC prognostic biomarker. The study also suggests continued analyses of the relationships between genetic driver mutations and the composition of tumor stroma, as well as continued probing of marker-defined fibroblasts as NSCLC subset-specific modifiers of immune surveillance and outcome.

Quality of Life and Sexual Functioning After Vulvar Reconstruction With the Lotus Petal Flap.

OBJECTIVE: Resection of (pre) malignant lesions in the vulvoperineal area may result in large defects that cannot be closed primarily. The lotus petal flap technique is widely used for reconstruction. The aim of this study was to evaluate both quality of life (QoL) and sexual functioning of patients who underwent the lotus petal flap procedure, because no data are available on this topic. METHODS: A cross-sectional study was performed on all eligible patients (N = 38) who underwent the lotus petal flap procedure between 2005 and 2016. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30, Female Sexual Function Index, and Body Image Scale were used to evaluate QoL and sexual functioning. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and Female Sexual Function Index scores were compared with scores of age-matched healthy women. RESULTS: Twenty-six patients (68%) responded. The mean (SD) age was 65.5 (16.3) years, and the median follow-up time was 38.5 months (range 16-141 months). Quality of life scores were lower compared with healthy women in the domains physical, role, and social functioning. Sexual activity rates were comparable with healthy women; however, sexual functioning was worse. Although patients were satisfied about their sexual life, pain was reported. CONCLUSIONS: Patients who underwent vulvar reconstructive surgery with lotus petal flaps seem to have a lower QoL compared with healthy women. Patients report more pain during sexual activity but are satisfied about their sexual functioning. These results should be included in preoperative counseling and follow-up of future patients eligible for vulvar reconstruction with a lotus petal flap.

Prognostic factors for local recurrence of squamous cell carcinoma of the vulva: A systematic review.

BACKGROUND: In patients treated for early-stage squamous cell vulvar carcinoma local recurrence is reported in up to 40% after ten years. Knowledge on prognostic factors related to local recurrences should be helpful to select high risk patients and/or to develop strategies to prevent local recurrences. OBJECTIVE: This systematic review aims to evaluate the current knowledge on the incidence of local recurrences in vulvar carcinoma related to clinicopathologic and cell biologic variables. DATA SOURCES: Relevant studies were identified by an extensive online electronic search in July 2017. STUDY ELIGIBILITY CRITERIA: Studies reporting prognostic factors specific for local recurrences of vulvar carcinoma were included. STUDY APPRAISAL AND SYNTHESIS METHODS: Two review authors independently performed data selection, extraction and assessment of study quality. The risk difference was calculated for each prognostic factor when described in two or more studies. RESULTS: Twenty-two studies were included; most of all were retrospective and mainly reported pathologic prognostic factors. Our review indicates an estimated annual local recurrence rate of 4% without plateauing. The prognostic relevance for local recurrence of vulvar carcinoma of all analyzed variables remains equivocal, including pathologic tumor free margin distance <8mm, presence of lichen sclerosus, groin lymph node metastases and a variety of primary tumor characteristics (grade of differentiation, tumor size, tumor focality, depth of invasion, lymphovascular space invasion, tumor localization and presence of human papillomavirus). CONCLUSIONS: Current quality of data on prognostic factors for local recurrences in vulvar carcinoma patients does not allow evidence-based clinical decision making. Further research on prognostic factors, applying state of the art methodology is needed to identify high-risk patients and to develop alternative primary and secondary prevention strategies.