Early decline of androgen levels in healthy adult men: an effect of aging per se? A prospective cohort study

Context Androgen levels have been shown to decline in aging men. However, there is no consensus on the effect of aging, (changes in) BMI, lifestyle factors and intercurrent disease. Objective Investigating longitudinal changes in serum androgen levels in healthy men in relation to body composition, lifestyle factors and intercurrent disease. Design, Setting, and Participants Longitudinal, population-based sibling pair study at a university research center. 999 healthy men aged 24-46 years of whom 691 were re-evaluated after a mean period of 12 years. Main outcome measures Serum SHBG, luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels measured using immuno-assays. Testosterone (T), estradiol (E2), dihydro-testosterone (DHT), androstenedione (Adione) measured using LC-MS/MS, free T calculated (cFT). Results Baseline age was 34±6 years. Mean BMI increased by 1.19kg/m², T levels decreased by 14.2%(20.8nmol/l vs. 17.8nmol/l), cFT by 19.1%(392pmol/l vs. 317pmol/l), DHT by 15.6%(1.5nmol/l vs.1.3nmol/l), and Adione by 10.7%(3.7nmol/l vs. 3.3nmol/l; all p<0.001). E2 did not change over time. SHBG increased by 3.0%(39.8nmol/l vs. 41.0nmol/l), LH by 5.8%(4.6U/l vs. 4.9U/l) and FSH by 14.7%(4.3U/l vs. 5.1U/l) (all p<0.001). For T, cFT, DHT, Adione and SHBG these longitudinal changes persisted after adjustment for confounders (all p<0.001). Conclusion Serum androgen levels start declining early during adult life and independently from changes in BMI and other lifestyle factors, suggesting that aging per se leads to an altered sex steroid status. Given the concurrent rise in gonadotropin levels, the decline in androgen status most likely arises from primary decrease in testicular function.

P14.76 Characteristics of anaplastic oligodendrogliomas short-term survivors: a POLA network study

BACKGROUND Although patients with 1p/19q codeleted anaplastic oligodendrogliomas (AO) usually have a prolonged survival, some patients have a poorer outcome. The aim of the present study was to analyze their characteristics. MATERIAL AND METHODS The characteristics of AO patients with a survival < 5 years included in the POLA network were analyzed and compared to those of AO patients with a survival > 5 years. RESULTS In January 2019, among the 519 patients AO patients included in the POLA network, 55 patients were short-term survivors and 146 patients had a survival > 5 years. Among the 55 AO short-term survivors, 44 patients (80%) died from tumor progression and 11 patients (20%) from another cause (suicide n=2, toxicity n=2, intercurrent disease n=6, other n=1). Compared to > 5 years survivors, short-term survivors were older (57 years vs 48 years, p<0.001) and less frequently presented with isolated seizures (9% vs 33%, p=0.0017). They presented with tumors that more frequently involved multiple lobes (66% vs 47%, p=0.03), had a higher rate of nuclear atypia (80% vs 48%, p<0.001), a higher proliferative index (Ki67, 26% vs 18%, p<0.001), a higher level of p53 expression (10.8% vs 3.9% p<0.001), and had a higher rate of chromosomal abnormalities (91% vs 71% p=0.008). Compared to > 5 years survivors, short-term survivors less frequently underwent a surgical resection (64% vs 89% p<0.001) and their initial treatment more frequently consisted in temozolomide chemotherapy alone (41% vs 20% p=0.008). CONCLUSION AO short-term survivors are associated with distinct clinical, radiological, histological and molecular characteristics at diagnosis.

Dysgerminoma of the ovary: Review of 32 cases

16072 Purpose: This study was undertaken to determine the frequency, characteristics, treatment and outcome of patients with dysgerminomas in single institution between 1990 and 2006. Methods: A total of 32 patients with pure dysgerminoma were retrospectively reviewed, among whom 23 patients had primary treatment in NNBRCRC during the period 1990–2006 and referred for follow-up (n=1) or salvage therapy after recurrence (n=9). Results: The median (range) age at presentation was 21 (14–42) years. 17 women (53%) presented with FIGO surgical stage I disease, 2 (6%) had pelvic metastases (stage II), and 9 (28%) had advanced (stage III/IV) disease. 4 patients had no comprehensive surgical staging. 2 women had evidence of dysgenetic gonads with a 46 XY karyotype. Primary surgery was done in all patients. 22 patients (69%) underwent fertility-sparing surgery. 4 (13%) patients received no adjuvant treatment after surgery due to stage Ia. All of them are alive without evidence of disease at a median (range) follow-up of 4,2 (2–6,4) years. Postoperative systemic chemotherapy was administered to 28 (87%) women. 16 of them received adjuvant chemotherapy and 12 received chemotherapy for metastatic disease. Among them 20 received platinum-based chemotherapy. Six patients had disease progression during first-line systemic treatment, all women received non-platinum-based chemotherapy. Three of them were salvage with second-line cisplatinum-based chemotherapy. Two deaths were associated with progressive disease, and one patient died of intercurrent disease. Overall, 29 women (90%) are alive without evidence of disease at a median follow-up of 68 months. Conclusions: Our date confirmed that the majority of patients can be managed with fertility sparing surgery and platinum-based adjuvant treatment without compromising survival. No significant financial relationships to disclose.

Risk of Death From Intercurrent Disease Is Not Excessively Increased by Modern Postoperative Radiotherapy for High-Risk Resected Non–Small-Cell Lung Carcinoma

PURPOSE: Some studies report a high risk of death from intercurrent disease (DID) after postoperative radiotherapy (XRT) for non–small-cell lung cancer (NSCLC). This study determines the risk of DID after modern-technique postoperative XRT. PATIENTS AND METHODS: A total of 202 patients were treated with surgery and postoperative XRT for NSCLC. Most patients (97%) had pathologic stage II or III disease. Many patients (41%) had positive/close/uncertain resection margins. The median XRT dose was 55 Gy with fraction size of 1.8 to 2 Gy. The risk of DID was calculated actuarially and included patients who died of unknown/uncertain causes. Median follow-up was 24 months for all patients and 62 months for survivors. RESULTS: A total of 25 patients (12.5%) died from intercurrent disease, 16 from confirmed noncancer causes and nine from unknown causes. The 4-year actuarial rate of DID was 13.5%. This is minimally increased compared with the expected rate for a matched population (approximately 10% at 4 years). On multivariate analysis, age and radiotherapy dose were borderline significant factors associated with a higher risk of DID (P = .06). The crude risk of DID for patients receiving less than 54 Gy was 2% (4-year actuarial risk 0%) versus 17% for XRT dose ≥ 54 Gy. The 4-year actuarial overall survival was 34%; local control was 84%; and freedom from distant metastases was 37%. CONCLUSION: Modern postoperative XRT for NSCLC does not excessively increase the risk of intercurrent deaths. Further study of postoperative XRT, particularly when using more sophisticated treatment planning and reasonable total doses, for carefully selected high-risk resected NSCLC is warranted.

Ventriculofemoroatrial shunt: a viable alternative for the treatment of hydrocephalus

✓ Children with shunted hydrocephalus often have a myriad of other medical conditions. When these concomitant problems involve the pleura, peritoneum, and/or the venous system, placement of the distal catheter may prove to be problematic. This report presents preliminary results in three hydrocephalic children following ventriculofemoroatrial shunt placement. The peritoneal and pleural cavities in each of these children were compromised and there was no vascular access into the superior vena cava due to intercurrent disease. An alternative technique for ventriculoperitoneal shunt placement was performed via the femoral vein. Fluoroscopic guidance was used to confirm the intraatrial position of the distal end of the shunt catheter. Follow-up review to date shows no complications. This newly described technique provides a feasible alternative to distal shunt catheter placement in patients in whom more traditional sites are unavailable.