ALP bouncing and LDH normalization in bone metastatic castration-resistant prostate cancer patients under therapy with Enzalutamide: an exploratory analysis

BackgroundIn bone metastatic castration-resistant prostate cancer (bmCRPC) treated with Enzalutamide commonly used prostate-specific antigen (PSA) can be misleading since initial PSA-flares may occur. In other therapies, bouncing of alkaline phosphatase (ALP-bouncing) was shown to be a promising surrogate for survival outcome. Low lactate dehydrogenase (LDH) is usually associated with better outcome. We evaluated the prognostic ability of ALP-bouncing, LDH, PSA, and the combination of these markers after initiation of Enzalutamide.MethodsEighty-nine patients with bmCRPC and dynamic changes of PSA, LDH and ALP were analyzed. ALP-bouncing, an increase after therapy start followed by a decline below baseline during the first 8 weeks, LDH-normalization and PSA-decline were analyzed regarding their association with survival using Kaplan-Meier analyses and uni- and multivariate (UV and MV) Cox-regression models.ResultsIn Kaplan-Meier analysis a PSA-decline >50%, LDH-normalization and ALP-bouncing were associated with longer median progression-free survival (PFS) with 7 [95% confidence interval (CI): 4.2–9.8] vs. 3 (2.3–3.7) months for PSA-decline (log-rank P<0.01), 6 (4.1–8) vs. 2 (1.2–2.8) for LDH-normalization (P<0.01) and 8 (0–16.3) vs. 3 (1.9–4.1) for ALP-bouncing (P=0.01). Analysis of overall survival (OS) showed similar, not for all parameters significant, results with 17 (11.7–22.3) vs. 12 (7.0–17.1) months for PSA (P=0.35), 17 (13.2–20.8) vs. 7 (5.8–8.2) for LDH-normalization (P<0.01) and 19 (7.9–30.1) vs. 12 (7.7–16.3) for ALP-bouncing (P=0.32). In UV analysis, ALP-bouncing [hazard ratio (HR): 0.5 (0.3–1.0); P=0.02], PSA-decline >50% [HR: 0.5 (0.3–0.7); P<0.01] and LDH-normalization [HR: 0.4 (0.2–0.6); P<0.01] were significantly associated with longer PFS. For OS, LDH-normalization significantly prognosticated longer survival [HR: 0.4 (0.2–0.6); P<0.01]. In MV analysis, LDH-normalization was associated with a trend towards better OS [HR: 0.5 (0.2–1.1); P=0.09]. Comparing ALP-bouncing, LDH-normalization and PSA-decline with a PSA-decline alone, Kaplan-Meier analysis showed significantly longer PFS [11 (0.2–21.8) vs. 4 (0–8.6); P=0.01] and OS [20 (17.7–22.3) vs. 8 (0.3–15.7); P=0.02] in favor of the group presenting with the beneficial dynamics of all three markers. In UV analysis, the presence of favorable changes in the three markers was significantly associated with longer PFS [HR: 0.2 (0.1–0.7); P<0.01] and OS [HR: 0.3 (0.1–0.8); P=0.02].ConclusionsALP-bouncing and LDH-normalization may add to identification of bmCRPC-patients with favorable prognosis under Enzalutamide.     

Patient‐reported outcome measures and their utility in the management of patients with advanced chronic kidney disease

Symptom and quality of life (QOL) measures in patients with advanced chronic kidney disease are recognized indicators of patient‐centred care and represent important research, quality and clinical measures. This study examined relationships between symptom burden, QOL and functional status and associations of symptoms and mortality risk. A multisite longitudinal cohort analysis was undertaken in chronic kidney disease stage 4/5 (no dialysis) and dialysis patients. Patients completed symptom and QOL measures (Palliative Care Outcome Symptom Score renal), World Health Organisation QOL Brief Version) and Karnofsky Performance scale. Clinical and demographic data were recorded.     

Real‐world effectiveness of fulvestrant monotherapy as first endocrine treatment in patients with metastatic breast cancer

Fulvestrant monotherapy is approved for postmenopausal women with hormone receptor‐positive, metastatic breast cancer (MBC) who progressed following antiendocrine therapy, or those with hormone receptor‐positive, human epidermal receptor 2‐negative advanced breast cancer (BC) not previously treated with endocrine therapy (ET). However, real‐world data are lacking. Retrospective reviews of 10 United States community oncology practices identified patients diagnosed with MBC between 1 January 2011 and 31 December 2015 who received fulvestrant as the first ET, either as initial therapy for metastatic disease or after progression following one line of chemotherapy. Endpoints were progression‐free survival (PFS) and overall survival (OS). Patients were classified as ET‐naïve or by relapse status following adjuvant ET (“early” recurrence during or ≤12 months of completing adjuvant ET, or “late” >12 months after completing adjuvant ET). Outcomes were evaluated using Kaplan‐Meier methods. Among 121 patients, median PFS (95% confidence interval) was 8.3 months (4.8‐12.3) for early relapse, 15.4 months (10.2‐21.2) for late relapse, and 18.7 months (10.1‐20.8) among ET‐naïve patients (P = .018). Median OS was 39.8 months (25.0‐55.1) for early relapse and 61.4 months (47.1‐61.4) for late relapse, but was not reached (NR; 55.6–NR) for ET‐naïve patients (P = .002). Fulvestrant monotherapy as the first ET after MBC diagnosis demonstrates PFS comparable to clinical study results; outcomes appeared better in patients without prior ET exposure and in patients with disease recurrence >12 months following adjuvant ET. These findings support fulvestrant monotherapy in patients with hormone receptor‐positive MBC.     

Role of C11-FDG dual-tracer PET-CT scan in metastatic screening of hepatocellular carcinoma—a cost-effectiveness analysis

BackgroundWe aimed to identify predictive factors for positron emission tomography (PET)-detected hepatocellular carcinoma (HCC) metastasis and a cost-effective approach to preoperative PET-computed tomography (CT) for detecting metastasis.MethodsClinicopathological and survival data of HCC patients having PET-CT with 18F-fludeoxyglucose (FDG) and 11C-acetate (ACT) following contrast-enhanced CT/magnetic resonance imaging (MRI) for preoperative tumor staging were reviewed. Binary logistic regression was performed to identify predictive factors for PET-detected metastasis. A cost-benefit analysis model was built for the incurred costs and the impact of PET-CT findings on treatment strategy was studied.ResultsTotally 152 patients were analyzed. Dual-tracer PET-CT detected metastasis in 17 patients (11%). By multivariate analysis, alpha-fetoprotein (AFP) ≥400 ng/mL [relative risk (RR): 4.30, 95% confidence interval (CI): 1.41–13.15, P=0.011] and bilobar disease (RR: 3.94, 95% CI: 1.24–12.52, P=0.014) were independent predictive factors for PET-detected metastasis. PET-CT findings altered the treatment strategy for 12 patients (7.9%); three partial hepatectomies, eight episodes of transarterial chemoembolization (TACE) and one episode of ablation were avoided, with an estimated cost-saving of US $91,000, $150,000 and $10,600 respectively. Had the PET-CT been performed only for patients with AFP ≥400 ng/mL or bilobar disease (n=74), metastasis would have been confirmed in 14 patients (18.9%), and the cost-saving per patient was estimated at US $1,070.ConclusionsDual-tracer PET-CT is cost-effective and useful for preoperative HCC staging in patients with AFP ≥400 ng/mL or bilobar disease. Its routine use in preoperative workup for all HCC patients is not recommended. Unilobar disease with AFP <400 ng/mL can achieve good negative predictive value for PET-detected metastasis. Screening patients with either factor can avoid unnecessary procedures and is thus cost-effective for preoperative HCC workup.     

Tubulointerstitial nephritis and IgA nephropathy in a patient with advanced lung cancer treated with long-term gefitinib

A 52-year-old Japanese female was admitted to our hospital for microhematuria, proteinuria and progressive renal dysfunction. Two years prior to admission, she was diagnosed with lung adenocarcinoma and multiple bone and brain metastases, and was treated with gefitinib (250 mg/day). Treatment for 6 months induced partial response with 30% regression of the primary lung tumor, and resolution of metastatic tumors. After confirmation of the partial remission state, we performed percutaneous renal biopsy. Glomeruli showed mild to moderate mesangial proliferation, segmental endocapillary proliferation and occasional fibrocellular crescent formation. In addition, severe interstitial fibrosis and tubular atrophy relative to the degree of glomerular sclerosis were noted. Immunofluorescence microscopy showed predominant IgA deposition in the mesangial area. Electron microscopy revealed subepithelial and paramesangial electron-dense deposits. In consideration of the prognosis of lung cancer and complication of immunosuppressive treatment, we continued gefitinib only and closely followed-up the clinical course in the outpatient clinic. Sixteen months later, she continued to have proteinuria and microhematuria, and the severity of renal dysfunction was still the same. However, the lung cancer started to increase in size. This is quite an unusual case presenting histologically with tubulointerstitial nephritis and IgA nephropathy in a patient on long-term treatment with gefitinib.