Symptoms of anxiety but not depression before start of taxane-based chemotherapy are associated with peripheral neuropathy: a multicenter study in women with breast cancer.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy, especially after taxane-based therapy. This study aimed to examine the relationship between symptoms of anxiety and depression before the start of taxane-based chemotherapy and the development of CIPN in women with breast cancer. METHODS: In this prospective study, women with breast cancer receiving taxane-based (neo)adjuvant chemotherapy were recruited from four hospitals in the Netherlands. Patients completed questionnaires assessing anxiety and depressive symptoms before treatment and CIPN before treatment (T0), 6 weeks after start of treatment (T1), after the last cycle of chemotherapy (T2), and 6 months after the end of treatment (T3). Mixed model analyses were used to investigate whether medium/high levels of anxiety or depression at baseline are associated with the level of CIPN during and after treatment. RESULTS: Among the 61 participating women, 14 (23%) reported medium/high levels of anxiety and 29 (47.5%) reported medium/high levels of depressive symptoms at baseline. The group of women with medium/high baseline levels of anxiety showed a significantly higher increase in CIPN during and after chemotherapy than women with low baseline levels of anxiety (p < .001). No relationship between depressive symptoms at baseline and the development of CIPN was found. CONCLUSION: This study showed that baseline medium to high levels of anxiety but not depressive symptoms impacted the development of CIPN during and in the 6 months after treatment.

High-Intensity Care in the End-of-Life Phase of Castration-Resistant Prostate Cancer Patients: Results from the Dutch CAPRI-Registry.

Background: Intensive end-of-life care (i.e., the overuse of treatments and hospital resources in the last months of life), is undesirable since it has a minimal clinical benefit with a substantial financial burden. The aim was to investigate the care in the last three months of life (end-of-life [EOL]) in castration-resistant prostate cancer (CRPC). Methods: Castration-resistant prostate cancer registry (CAPRI) is an investigator-initiated, observational multicenter cohort study in 20 hospitals retrospectively including patients diagnosed with CRPC between 2010 and 2016. High-intensity care was defined as the initiation of life-prolonging drugs (LPDs) in the last month, continuation of LPD in last 14 days, >1 admission, admission duration ≥14 days, and/or intensive care admission in last three months of life. Descriptive and binary logistic regression analyses were performed. Results: High-intensity care was experienced by 41% of 2429 patients in the EOL period. Multivariable analysis showed that age (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.97-0.99), performance status (OR 0.57, 95% CI 0.33-0.97), time from CRPC to EOL (OR 0.98, 95% CI 0.97-0.98), referral to a medical oncologist (OR 1.99, 95% CI 1.55-2.55), prior LPD treatment (>1 line OR 1.72, 95% CI 1.31-2.28), and opioid use (OR 1.45, 95% CI 1.08-1.95) were significantly associated with high-intensity care. Conclusions: High-intensity care in EOL is not easily justifiable due to high economic cost and little effect on life span, but further research is awaited to give insight in the effect on patients' and their caregivers' quality of life.

Neoadjuvant Treatment with Angiogenesis-Inhibitor Dovitinib Prior to Local Therapy in Hepatocellular Carcinoma: A Phase II Study.

BACKGROUND: Hepatocellular carcinoma (HCC) recurrence rates following locoregional treatment are high. As multireceptor tyrosine kinase inhibitors targeting vascular endothelial growth factor receptors (VEGFRs) are effective in advanced HCC, we assessed the efficacy and safety of neoadjuvant systemic treatment with dovitinib in early- and intermediate-stage HCC. MATERIALS AND METHODS: Twenty-four patients with modified Child-Pugh class A early- and intermediate-stage HCC received neoadjuvant oral dovitinib 500 mg daily (5 days on/2 days off) for 4 weeks, followed by locoregional therapy. Primary endpoints were objective response rates and intratumoral blood flow changes. Secondary endpoints were safety, pharmacodynamical plasma markers of VEGFR-blockade, time to progression (TTP), and overall survival (OS). RESULTS: Modified RECIST overall response rate was 48%, including 13% complete remission, and despite dose reduction/interruption in 83% of patients, intratumoral perfusion index decreased significantly. Grade 3-4 adverse events, most frequently (on-target) hypertension (54%), fatigue (25%), and thrombocytopenia (21%), occurred in 88% of patients. Plasma VEGF-A, VEGF-D, and placental growth factor increased significantly, whereas sTie-2 decreased, consistent with VEGFR-blockade. Following neoadjuvant dovitinib, all patients could proceed to their original planned locoregional treatment. No delayed toxicity occurred. Seven patients (three early, four intermediate stage) underwent orthotopic liver transplant after median 11.4 months. Censoring at transplantation, median TTP and OS were 16.8 and 34.8 months respectively; median cancer-specific survival was not reached. CONCLUSION: Already after a short 4-week dovitinib treatment period, intratumoral blood flow reduction and modest antitumor responses were observed. Although these results support use of systemic neoadjuvant strategies, the poor tolerability indicates that dovitinib dose adaptations are required in HCC. IMPLICATIONS FOR PRACTICE: Orthotopic liver transplantation may cure early and intermediate-stage hepatocellular carcinoma. Considering the expected waiting time >6 months because of donor liver scarcity, there is an unmet need for effective neoadjuvant downsizing strategies. Angiogenesis inhibition by dovitinib does not negatively affect subsequent invasive procedures, is safe to administer immediately before locoregional therapy, and may provide a novel treatment approach to improve patient outcomes if tolerability in patients with hepatocellular carcinoma can be improved by therapeutic drug monitoring and personalized dosing.

Real-world Outcomes of Sequential Androgen-receptor Targeting Therapies with or Without Interposed Life-prolonging Drugs in Metastatic Castration-resistant Prostate Cancer: Results from the Dutch Castration-resistant Prostate Cancer Registry.

BACKGROUND: Cross resistance between androgen-receptor targeting therapies (ARTs) (abiraterone acetate plus prednisone [ABI+P] or enzalutamide [ENZ]) for treatment of metastatic castration-resistant prostate cancer (mCRPC) may affect responses to second ART (ART2). OBJECTIVE: To establish treatment duration and prostate-specific antigen (PSA) response of ART2 in real-world mCRPC patients treated with or without other life-prolonging drugs (LPDs; ie, docetaxel, cabazitaxel, or radium-223) between ART1 and ART2. DESIGN, SETTING, AND PARTICIPANTS: Castration-resistant prostate cancer patients, diagnosed between 2010 and 2016 were retrospectively registered in Castration-resistant Prostate Cancer Registry (CAPRI). Patients treated with both ARTs were clustered into two subgroups: ART1>ART2 or ART1>LPD>ART2. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcomes were ≥50% PSA response and treatment duration of ART2. Descriptive statistics and binary logistic regression after multiple imputations were performed. RESULTS AND LIMITATIONS: A total of 273 patients were included with a median follow-up of 8.4 mo from ART2. Patients with ART1>ART2 were older and had favourable prognostic characteristics at ART2 baseline compared with patients with ART1>LPD>ART2. No differences between ART1>ART2 and ART1>LPD>ART2 were found in PSA response and treatment duration. Multivariate analysis suggested that PSA response of ART2 was less likely in patients with visceral metastases (odds ratio [OR] 0.143, p=0.04) and more likely in patients with a relatively longer duration of androgen-deprivation treatment (OR 1.028, p=0.01) and with ABI + P before ENZ (OR 3.192, p=0.02). A major limitation of this study was missing data, a common problem in retrospective observational research. CONCLUSIONS: The effect of ART2 seems to be low, with a low PSA response rate and a short treatment duration irrespective of interposed chemotherapy or radium-223, especially in patients with short time on castration, visceral disease, and ENZ before ABI+P. PATIENT SUMMARY: We observed no differences in outcomes of patients treated with sequential abiraterone acetate plus prednisone (ABI+P) and enzalutamide (ENZ) with or without interposed chemotherapy or radium-223. In general, outcomes were lower than those in randomised trials, questioning the additional effect of second treatment with ABI+P or ENZ in daily practice.

Disclosing the Uncertainty Associated with Prognostic Estimates in Breast Cancer.

BACKGROUND: Treatment decision making is often guided by evidence-based probabilities, which may be presented to patients during consultations. These probabilities are intrinsically imperfect and embody 2 types of uncertainties: aleatory uncertainty arising from the unpredictability of future events and epistemic uncertainty arising from limitations in the reliability and accuracy of probability estimates. Risk communication experts have recommended disclosing uncertainty. We examined whether uncertainty was discussed during cancer consultations and whether and how patients perceived uncertainty. METHODS: Consecutive patient consultations with medical oncologists discussing adjuvant treatment in early-stage breast cancer were audiotaped, transcribed, and coded. Patients were interviewed after the consultation to gain insight into their perceptions of uncertainty. RESULTS: In total, 198 patients were included by 27 oncologists. Uncertainty was disclosed in 49% (97/197) of consultations. In those 97 consultations, 23 allusions to epistemic uncertainty were made and 84 allusions to aleatory uncertainty. Overall, the allusions to the precision of the probabilities were somewhat ambiguous. Interviewed patients mainly referred to aleatory uncertainty if not prompted about epistemic uncertainty. Even when specifically asked about epistemic uncertainty, 1 in 4 utterances referred to aleatory uncertainty. When talking about epistemic uncertainty, many patients contradicted themselves. In addition, 1 in 10 patients seemed not to realize that the probabilities communicated during the consultation are imperfect. CONCLUSIONS: Uncertainty is conveyed in only half of patient consultations. When uncertainty is communicated, oncologists mainly refer to aleatory uncertainty. This is also the type of uncertainty that most patients perceive and seem comfortable discussing. Given that it is increasingly common for clinicians to discuss outcome probabilities with their patients, guidance on whether and how to best communicate uncertainty is urgently needed.

Validity of Adjuvant! Online program in older patients with breast cancer: a population-based study.

BACKGROUND: Adjuvant! Online is a prediction tool that can be used to aid clinical decision making in patients with breast cancer. It was developed in a patient population aged 69 years or younger, and subsequent validation studies included small numbers of older patients. Since older patients with breast cancer differ from younger patients in many aspects, the aim of this study was to investigate the validity of Adjuvant! Online in a large cohort of unselected older patients. METHODS: We included patients from the population-based FOCUS cohort, which included all consecutive patients aged 65 years or older who were diagnosed with invasive or in-situ breast cancer between Jan 1, 1997, and Dec 31, 2004, in the southwestern part of the Netherlands. We included all patients who fulfilled the criteria as stated by Adjuvant! Online: patients with unilateral, unicentric, invasive adenocarcinoma; no evidence of metastatic or residual disease; no evidence of T4 features; and no evidence of inflammatory breast cancer. We entered data from all patients with the "average for age" comorbidity status (model 1) and with an individualised comorbidity status (model 2). FINDINGS: We included 2012 patients. Median age of patients in the cohort was 74·0 years (IQR 69·0-79·0). 904 (45%) of 2012 patients died during follow-up, whereas 326 (16%) patients had recurrence. Median follow-up for overall survival was 9·0 years (IQR 7·4-10·7), and 6·6 years (4·4-6·6) for patients without recurrence. Using model 1, Adjuvant! Online overestimated 10-year overall survival by 9·8% ([95% CI 5·9-13·7], p<0·0001) and 10-year cumulative recurrence survival by 8·7% ([6·7-10·7], p<0·0001). By contrast, when using model 2, Adjuvant! Online underestimated the 10-year overall survival by -17·1% ([95% CI -21·0 to -13·2], p<0·0001). However, when using model 2, Adjuvant! Online predicted cumulative recurrence accurately in all patients (-0·7% [95% CI -2·7-1·3], p=0·48). INTERPRETATION: Adjuvant! Online does not accurately predict overall survival and recurrence in older patients with early breast cancer. FUNDING: Dutch Cancer Foundation.

False-positive serum human chorionic gonadotropin (HCG) in a male patient with a malignant germ cell tumor of the testis: a case report and review of the literature.

A 39-year-old male patient with a favorable prognosis stage IIB metastatic malignant germ cell tumor (GCT) and elevated pre- and postorchiectomy serum human chorionic gonadotropin (hCG) was treated with three courses of combination chemotherapy resulting in a rapid normalization of his serum hCG. Within 2 months after the cessation of chemotherapy, his serum hCG increased again, suggesting tumor recurrence. Pathological examination of the resected residual retroperitoneal lymph nodes revealed no vital tumor cells. Based on the further rise in his serum hCG and enlargement of mediastinal lymph nodes on computed tomography scan, the patient underwent second- and third-line chemotherapy, which did not result in normalization of his serum hCG. Reanalysis of stored serum samples with other immunoassays revealed that the elevated serum hCG levels collected before first-line chemotherapy were indeed elevated, but those collected after first-line chemotherapy were all falsely positive. Currently, the patient is still alive and disease free. This is the first report of a male cancer patient who received unneeded second- and third-line chemotherapy for relapse based on false-positive hCG results. We discuss the pitfalls of false-positive serum hCG measurements, including heterophilic antibodies, as in our IgA-deficient patient, and review the literature.