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• Identifying variables that predict the prognosis of patients with SCLC is important. • 18F-FDG PET/CT influences staging of patients with SCLC. • Metabolic parameters could be used as predictors for PFS and OS.

Purpose Despite the efficacy of abiraterone, a CYP17A1 inhibitor, in metastatic castration-resistant prostate cancer (CRPC), nearly all patients develop resistance. The purpose of this phase II study was to evaluate mechanisms of resistance to more complete androgen synthesis inhibition with abiraterone and dutasteride. Experimental Design Eligible metastatic CRPC patients underwent a baseline metastasis biopsy. Patients received abiraterone and prednisone for two 4-week cycles. After this time, high-dose dutasteride (3.5mg daily) was added. Patients continued therapy until study withdrawal or radiographic progression. Repeat metastasis biopsy was obtained at progression. The primary endpoint was to assess mechanisms of resistance. Serum hormone and abiraterone levels were assessed. Tissue was assessed for androgen receptor (AR) and AR splice variant-7 (ARV7) expression. Results Forty patients were enrolled. 60% (n=24) achieved a ≥50% reduction in PSA. The median time to radiographic progression was 11 months. Nearly all baseline (n=29/30) and post-treatment (n=16/16) tumors tested for AR nuclear expression were positive. Of those tested, ARV7 expression was present in 48% (n=10/21) of baseline and 42% (n=5/12) of treatment discontinuation specimens. Compared to patients with higher serum abiraterone levels at treatment discontinuation, patients with lower levels had higher circulating androgens. Conclusions Despite increased androgen synthesis inhibition, we demonstrate that tumor AR axis remains important in disease progression. We highlight that abiraterone metabolism and pharmacokinetics may play a role in resistance. The non-comparative design limits conclusions on the efficacy of dual therapy with abiraterone and dutasteride, but the results support development of further multifaceted approaches towards AR inhibition.

Background: Family history of Alzheimer’s disease (AD) is associated with increased dementia-risk. Objective: The Israel Registry for Alzheimer’s Prevention (IRAP) is a prospective longitudinal study of asymptomatic middle-aged offspring of AD patients (family history positive; FH+) and controls (whose parents have aged without dementia; FH–) aimed to unravel the contribution of midlife factors to future cognitive decline and dementia. Here we present the study design, methods, and baseline characteristics. Methods: Participants are members of the Maccabi Health Services, 40–65 years of age, with exquisitely detailed laboratory, medical diagnoses and medication data available in the Maccabi electronic medical records since 1998. Data collected through IRAP include genetic, sociodemographic, cognitive, brain imaging, lifestyle, and health-related characteristics at baseline and every three years thereafter. Results: Currently IRAP has 483 participants [mean age 54.95 (SD = 6.68) and 64.8% (n = 313) women], 379 (78.5%) FH+, and 104 (21.5%) FH–. Compared to FH–, FH+ participants were younger (p = 0.011), more often males (p = 0.003) and with a higher prevalence of the APOE E4 allele (32.8% FH+, 22% FH–; p = 0.040). Adjusting for age, sex, and education, FH+ performed worse than FH–in global cognition (p = 0.027) and episodic memory (p = 0.022). Conclusion: Lower cognitive scores and higher rates of the APOE E4 allele among the FH+ group suggest that FH ascertainment is good. The combination of long-term historical health-related data available through Maccabi with the multifactorial information collected through IRAP will potentially enable development of dementia-prevention strategies already in midlife, a critical period in terms of risk factor exposure and initiation of AD-neuropathology.

Lutetium-177-PSMA ([177Lu]-PSMA-617), a radiolabeled small molecule, binds with high affinity to prostate-specific membrane antigen (PSMA), enabling targeted radiation therapy to metastatic prostate lesions. Our objective was to retrospectively analyze the activity of [177Lu]-PSMA-617 given off-trial to men with metastatic castration resistant prostate cancer (mCRPC) and identify clinical factors associated with PSA response. Electronic medical records of all men treated with [177Lu]-PSMA-617 were reviewed and analyzed. Overall survival was calculated using the Kaplan–Meier method. The association between potential variables and PSA response was analyzed by univariate analysis, using either logistic regression or χ2/Fisher’s exact test. Multivariable analysis was carried out using logistic regression on all categorical variables with a P-value of <0.1 on univariate analysis. Variables found to be statistically significant were then used to define a categorical score. A total of 52 patients received at least one cycle of [177Lu]-PSMA-617. Clinical benefit was observed in 28 patients (52%). PSA decline ≥20% and ≥50% was observed in 26 (50%) and 18 patients (35%), respectively. Achievement of any PSA decline at first measurement was significantly associated with survival. There was a negative association between the number of previous chemotherapy lines and PSA decline above 20%. Univariate analysis followed by multivariable analysis showed that older age and higher hemoglobin were significantly associated with a PSA decline >20%. A score combining these two parameters was significantly associated with PSA response. In summary, [177Lu]-PSMA-617 is active in the ‘real-life’ setting of heavily pretreated men with mCRPC.

• Identifying variables that predict the prognosis of patients with NSCLC is important. • SUVmax in primary lung tumour is a useful independent prognostic variable. • (CTvol) is an independent prognostic variable if no lymph nodes are involved.