Old age as risk indicator for poor end-of-life care quality – A population-based study of cancer deaths from the Swedish Register of Palliative Care

BackgroundIf patient age affects the quality of end-of-life care in cancer is unknown. Using data from a population-based register of palliative care in Sweden, we addressed this question.MethodsThis nation-wide study focused on the last week of life of adults dying from cancer in 2011–2012, based on data reported to a national quality register for end-of-life care (N = 26,976). We specifically investigated if age-dependent differences were present with respect to thirteen indicators of palliative care quality. Patients were categorised in one out of five pre-defined age groups. Odds ratios (OR) with 95% confidence intervals (CIs), adjusted for type of end-of-life care unit, were calculated using logistic regression, with the oldest group as reference.FindingsAge-dependent differences in implementation rate were detected for ten out of thirteen end-of-life care quality indicators, most of which were progressively less well met with each increment in age group. Compared to elderly cancer patients, young patients were more often informed about imminent death, (OR, 3.9; 95% CI 2.5–5.9, p < 0.001), were more often systematically assessed for the presence and severity of pain (OR, 1.6; 95% CI 1.2–2.1, p < 0.001) or other symptoms (OR, 1.4; 95% CI 1.0–1.9, p = 0.044), were more likely to be assessed by palliative care consultation services (OR, 4.3; 95% CI 3.3–5.7, p < 0.001) and to have injections prescribed as needed against pain (OR, 3.4; 95% CI 1.3–9.4, p = 0.016), anxiety (OR, 3.8; 95% CI 2.0–7.1, p < 0.001) or nausea (OR, 3.6; 95% CI 2.3–5.7, p < 0.001). The families of young patients were more likely to be informed about imminent death (OR, 2.6; 95% CI 1.5–4.3, p = 0.001) and to be offered bereavement support (OR, 4.6; 95% CI 2.7–7.8, p < 0.001).InterpretationOld age is a risk indicator for poor end-of-life care quality among cancer patients in Sweden.FundingThe executive committee of the National Quality Registries in Sweden.     

Prognostic value of microsatellite instability (MSI) and PTEN expression in women with endometrial cancer: Results from studies of the NCIC Clinical Trials Group (NCIC CTG)

AimThe impact of PTEN status and microsatellite instability (MSI) on the prognosis of women with endometrial cancer is controversial. The aim of this study was to investigate MSI and PTEN expression in two patient populations using data from NCIC CTG studies.MethodsArchival paraffin embedded tumour from women with endometrial cancer enrolled in NCIC CTG studies: EN5 (stage I/II) and IND 126, 148 and 160 (advanced/recurrent disease) were examined for MSI using BAT25/26 and for PTEN expression using immunohistochemistry. PTEN and MSI status were correlated with clinicopathologic variables and survival using data from NCIC CTG trial databases.ResultsPTEN and MSI results were available from 128 and 163 patients, respectively. MSI+ tumours were more common in women enrolled in EN5 compared to the IND studies (p = 0.01). PTEN negative tumours were associated with improved survival in both univariate (hazard ratio (HR) 0.55, 95% confidence interval (CI) 0.32–0.94; p = 0.03) and multivariate (adjusted HR 0.54, 95% CI 0.30–0.96; p = 0.03) analyses in women enrolled in IND studies. Microsatellite stable tumours were associated with an improved prognosis in univariate (HR 0.18, 95% CI 0.06–0.51; p < 0.0001) and multivariate (adjusted HR 0.16, 95% CI 0.05–0.5; p < 0.0001) analyses in women enrolled in EN5. There was no significant correlation between MSI and PTEN status.ConclusionsPTEN negative tumours in women with advanced disease are associated with improved survival. MSI+ tumours are more common in early stage disease and in this group of women are associated with a worse prognosis.     

Long-term oncologic outcomes after fertility-sparing management using oral progestin for young women with endometrial cancer (KGOG 2002)

ObjectiveTo analyse the long-term oncologic outcomes of a fertility-sparing management using oral progestin in young women with endometrial cancer.MethodsWe analysed 148 patients (age ? 40 years) with stage IA, grade 1, endometrioid adenocarcinoma of the uterus who underwent fertility-sparing management using daily oral medroxyprogesterone acetate (MPA) or megestrol acetate (MA).Results115 (77.7%) showed complete response (CR) to progestin treatment, and 35 (30.4%) of them experienced recurrence after median follow-up time of 66 months. The 5-year recurrence-free survival was 68% (95% confidence interval [CI], 58.5–76.9%). However, 33 patients (22.3%) who failed to achieve CR underwent definitive surgical management, and no one had recurrence after median follow-up time of 41 months. During progestin treatment and at the time of recurrence, no patient showed clinical progression of disease over stage IA. Body mass index (BMI) ?25 kg/m² was the only significant factor associated with a failure to achieve CR (odds ratio [OR], 3.00; 95% CI, 1.35–6.66; P = 0.007). Upon multivariate analysis, BMI ? 25 kg/m² (OR, 2.14; 95% CI, 1.06–4.31; P = 0.033) was significantly associated with a higher risk of recurrence and the use of MPA (compared to MA) (OR, 0.44; 95% CI, 0.22–0.88; P = 0.021), maintenance treatment (OR, 0.22; 95% CI, 0.05–0.94; P = 0.042) and pregnancy (OR, 0.25; 95% CI, 0.11–0.56; P = 0.001) were significantly associated with a lower risk of recurrence.ConclusionFertility-sparing management was highly effective and safe. BMI < 25 kg/m², MPA (compared to MA), maintenance treatment and pregnancy were associated with higher possibility of long-term success.     

18-fluorodeoxy-glucose positron emission computed tomography as predictive of response after chemoradiation in oesophageal cancer patients

IntroductionThe purpose of this study was to evaluate if a baseline, an interim or a post-chemoradiation (CTRT) 18-fluorodeoxy-glucose positron emission computed tomography (18F-FDG PET/CT) studies could provide information on pathologic response to CTRT and overall survival (OS).Materials and methodsThirty-one patients with histologically proven adenocarcinoma or squamous cell carcinoma of the oesophagus, fit for trimodality therapy were prospectively enrolled. Most were men (93.5%), and had a stage III cancer (74.2%). Chemotherapy consisted of oxaliplatin/5-fluorouracil (45.2%) and taxane/5-fluorouracil (54.8%). All patients underwent a baseline, an interim (performed 12 ± 2 days after the onset of CTRT) and a post-CTRT 18F-FDG PET/CT study. The 18F-FDG PET/CT variables evaluated were at baseline, interim and post-CTRT studies maximum standardised uptake value (SUVmax) and total lesion glycolysis (TLG). Clinical and 18F-FDG PET/CT parameters were correlated with pathologic complete response (pathCR) and OS.ResultsAmong the 31 patients studied, 61.3% achieved a clinical complete response (cCR) and 87.1% had surgery. The median OS was 35.1 months (95% confidence interval (CI): 19.9–NA). PathCR rate was 22.2%. There was only a marginal association between cCR and pathCR (p = 0.06). None of the other variables was predictive of pathCR. There was association between OS and baseline TLG (p = 0.03) at the optimal cutoff TLG value of 75.15. Additionally, TLG and ΔTLG post-CTRT were also associated with OS (p = 0.01 and 0.03, respectively).ConclusionNone of the PET parameters is predictive of pathCR but TLG at baseline and post-CTRT are prognostic of OS.     

The risk of traumatic lumbar punctures in children with acute lymphoblastic leukaemia

BackgroundTraumatic lumbar punctures with blasts (TLP+) in children with acute lymphoblastic leukaemia (ALL) obscure central nervous system status and are associated with a poorer event-free survival (EFS).MethodsWe conducted a retrospective cohort study of all lumbar punctures (LPs) for children with ALL diagnosed at our institution from 2005 to 2009. We utilised random-effects and fixed-effects repeated-measures logistic regression analyses to identify risk factors for TLPs. Fixed-effects models use each patient as his or her own control. We used survival analysis to describe outcomes after a TLP+.Results264 children underwent 5267 evaluable lumbar punctures (LPs), of which 944 (17.9%) were traumatic. In the multivariable random-effects model, variables significantly associated with TLPs were age <1 year (odds ratio (OR) 3.46, 95% confidence interval (CI) 2.06–5.81) or age ⩾10 years (OR 2.00, CI 1.66–2.40); body mass index percentile ⩾95 (OR 1.44, CI 1.19–1.75); platelet count <100 × 10³/μL (OR 1.49, CI 1.08–20.7); fewer days since previous LP (OR 5.13, CI 2.34–11.25 for ⩾16 days versus 0–3 days); and a preceding TLP (OR 1.43, CI 1.19–1.73). In the fixed-effects model, image-guidance reduced the odds of TLP (OR 0.55, CI 0.32–0.95). The 5-year EFS (±SE) for children with TLP+ (77 ± 8%) was significantly lower than for children with CNS1 status (93 ± 2%; p = 0.002).ConclusionsThe frequency of TLP remains high. Consistent with previous studies, a TLP+ at diagnosis was associated with a poorer EFS. These risk factors can allow identifying interventions to reduce TLPs and directing interventions to those at highest risk.     

Local recurrence following breast-conserving treatment in women aged 40 years or younger: Trends in risk and the impact on prognosis in a population-based cohort of 1143 patients

AimTo evaluate trends in the risk of local recurrences after breast-conserving treatment (BCT) and to examine the impact of local recurrence (LR) on distant relapse-free survival in a large, population-based cohort of women aged ?40 years with early-stage breast cancer.MethodsAll women (n = 1143) aged ?40 years with early-stage (pT1-2/cT1-2, N0-2, M0) breast cancer who underwent BCT in the south of the Netherlands between 1988 and 2010 were included. BCT consisted of local excision of the tumour followed by irradiation of the breast.ResultsAfter a median follow-up of 8.5 (0.1–24.6) years, 176 patients had developed an isolated LR. The 5-year LR-rate for the subgroups treated in the periods 1988–1998, 1999–2005 and 2006–2010 were 9.8% (95% confidence interval (CI) 7.1–12.5), 5.9% (95% CI 3.2–8.6) and 3.3% (95% CI 0.6–6.0), respectively (p = 0.006). In a multivariate analysis, adjuvant systemic treatment was associated with a reduced risk of LR of almost 60% (hazard ratio (HR) 0.42; 95% CI 0.28–0.60; p < 0.0001). Patients who experienced an early isolated LR (?5 years after BCT) had a worse distant relapse-free survival compared to patients without an early LR (HR 1.83; 95% CI 1.27–2.64; p = 0.001). Late local recurrences did not negatively affect distant relapse-free survival (HR 1.24; 95% CI 0.74–2.08; p = 0.407).ConclusionLocal control after BCT improved significantly over time and appeared to be closely related to the increased use and effectiveness of systemic therapy. These recent results underline the safety of BCT for young women with early-stage breast cancer.     

Systematic analysis of early phase clinical studies for patients with breast cancer: Inclusion of patients with brain metastasis

PurposeThis systematic review aims to better define the limitations and patterns with which patients with MBC and CNS metastasis are enrolled into early phase developmental therapeutics trials.MethodsIn June 2016, PubMed search was conducted using the following keywords: “Breast cancer”. Drug-development phase 1, phase 2 or phase 1/2 trials for patients with MBC were included. Multiple-histology trials and trials without an efficacy endpoint were excluded.ResultsIn total, 1474 studies were included; Inclusion criteria for 423 (29%) allowed for CNS metastasis, 770 (52%) either excluded or did not document eligibility of patients with CNS disease. Trials accruing patients with HER2-positive MBC and including targeted therapies had higher odds of allowing for patients with CNS disease (adjusted OR 1.56, 95% CI 1.08–2.2.6; p = 0.019 and 1.49, 95% 1.08–2.06; p = 0.014, respectively). There were also higher odds of accrual of patients with CNS involvement into clinical trials over time (odds ratio = 1.10, 95% CI 1.07–1.12; p < 0.0001).ConclusionMost published early phase clinical trials either did not clearly document or did not allow for accrual of patients with CNS disease. Early phase trials with targeted agents or enrolling HER2+ MBC had higher odds of permitting CNS metastases.     

Effects of erlotinib first-line maintenance therapy versus placebo on the health-related quality of life of patients with metastatic non-small-cell lung cancer

IntroductionMaintenance therapy can delay progression and prolong survival in metastatic non-small-cell lung cancer (mNSCLC). As treatment for mNSCLC is non-curative, its impact on patient health-related quality of life (HRQoL) is an important consideration. SATURN (Sequential Tarceva in Unresectable NSCLC) was a randomised, double-blind, placebo-controlled, multicentre study investigating the impact of erlotinib maintenance therapy on HRQoL in patients with locally advanced or recurrent NSCLC.Patients and MethodsEligible patients who had previously completed four cycles of platinum-based chemotherapy were randomised 1:1 to receive erlotinib 150 mg/day or placebo until disease progression, unacceptable toxicity or death. Patient HRQoL was assessed using the Functional Assessment of Cancer Therapy-Lung questionnaire, in terms of time to symptom progression (TSP), time to deterioration (TTD) in Trial Outcome Index (TOI) and TTD. Exploratory analysis was based on time to analgesia and appearance of key symptoms (pain, cough and dyspnoea).ResultsCompared with placebo, erlotinib maintenance therapy prolonged progression-free and overall survival by 41% and 23%, respectively. At baseline, HRQoL measures were comparable between the two treatment groups. Maintenance therapy with erlotinib did not impact on deterioration in HRQoL: TSP (hazard ratio [HR] = 0.91 [95% confidence interval (CI) 0.74–1.12]; n = 785), TTD in TOI (HR = 1.06 [95% CI 0.87–1.31]; n = 781) and TTD in HRQoL (HR = 0.96 [95% CI 0.79–1.16]; n = 776). Time to pain and time to analgesic use were significantly delayed in patients receiving erlotinib compared with placebo (HR = 0.61 [95% CI 0.42–0.88]; p = 0.0080 and HR = 0.66 [95% CI 0.46–0.94]; p = 0.0199, respectively). A non-significant trend towards delayed time to cough and time to dyspnoea (HR = 0.77 [95% CI 0.49–1.21] and HR = 0.75 [95% CI 0.48–1.17], respectively) was also observed.ConclusionsErlotinib maintenance therapy significantly extends progression-free survival without compromising patient HRQoL in comparison with placebo, with some improvement in symptoms.     

Prior long response to androgen deprivation predicts response to next-generation androgen receptor axis targeted drugs in castration resistant prostate cancer

BackgroundThere is an urgent need for qualified predictive biomarkers of sensitivity for the treatments used in patients with castration-resistant prostate cancer (CRPC). We attempted to identify ready-to-use clinical predictors of improved outcome in metastatic CRPC (mCRPC) patients treated with next generation androgen receptor (AR) axis targeted drugs.Patients and methodsWe reviewed a cohort of patients who received AR axis targeted drugs for CRPC at two major French cancer centres. The predictive role of several clinical, biological and radiological parameters on progression-free survival (PFS) was studied.ResultsThe study cohort consisted of 173 patients. Median duration of response to initial androgen deprivation therapy (ADT) (time to castration resistance, TTCRPC) was 17.8 months. The 50% prostate-specific antigen (PSA) response rate to AR axis targeted drugs was 16% (95% confidence interval (CI): 6–27) and 41% (95% CI: 30–47) in patients with TTCRPC of under and over 12 months respectively (p = 0.005). Median PFS was 2.8 months (95% CI: 2.1–3.9) and 5.8 (95% CI: 4.6–7.8; HR: 0.58, p = 0.002). In patients treated with post-docetaxel enzalutamide (n = 57), median PFS was 2.8 months and 8.6 months, (Hazard ratio (HR) = 3.1; 95% CI: 1.6–5.8, p = 0.0016) according to TTCRPC, whereas no difference was observed in placebo-treated patients (n = 27). The 50% PSA response rate to enzalutamide was 8% (95% CI: 0–38) and 58% (95% CI: 42–73) in patients with a TTCRPC of under and over 12 months respectively (p < 0.001).ConclusionThe previous duration of response to ADT is a predictor of sensitivity to next generation AR axis targeted drugs in patients with mCRPC.     

Role of emphysema and airway obstruction in prognosis of lung cancer

Background and objectiveIt has been reported that the presence of COPD and emphysema is associated with an increased risk of lung cancer, but the prognosis significance of these two conditions is not well known. The aim of our study was to analyze the influence of COPD and emphysema in the prognosis of non-small cell lung cancer (NSCLC).MethodsThree hundred and fifty-three patients with cytohistologic diagnosis of NSCLC were prospectively collected. The relationship between survival at two years and the following variables: age, sex, smoking habit, comorbid diseases (cardiovascular diseases, previous tumour and COPD), weight loss, presence of emphysema on CT scan, performance status (PS) and treatment, was analyzed. The Kaplan–Meier method and log-rank test were used for survival analysis. A multivariate Cox proportional hazard model, stratified by TNM stage, was used to evaluate prognostic factors.ResultsEmphysema was present in 110 patients, associated with COPD in 78 (70.9%). In univariate analysis, survival decreased with age > 70 years (p = 0.01), presence of emphysema (p = 0.02), weight loss (p = 0.00001), PS ≥ 2 (p = 0.00001) and symptomatic treatment (p = 0.0001). Multivariate analyses identified emphysema (HR = 1.49 (95% CI 1.11–2.01)), PS ≥ 2 (HR = 2.12 (95% CI 1.31–3.38)) and treatment: surgery (HR = 0.3 (95% CI 0.15–0.56)) and chemotherapy (HR = 0.34 (95% CI 0.31–0.57)) as independent prognostic factors.ConclusionThe presence of emphysema affects the prognostic outcome of patients with non-small cell lung cancer. Emphysema should therefore be considered for prognostic studies on comorbidity.     

The elevated C-reactive protein level is associated with poor prognosis in prostate cancer patients treated with radiotherapy

BackgroundC-reactive protein (CRP) is a sensitive marker of inflammation that has been linked with prognosis in various solid tumours. In the present study, we analysed the prognostic relevance of elevated plasma CRP levels in prostate cancer patients treated with radiotherapy.MethodsA total of 261 prostate cancer patients treated with 3D-conformal radiotherapy were evaluated retrospectively. Cancer specific survival (CSS), overall survival (OS) and clinical disease-free survival (DFS) were assessed using Kaplan–Meier analysis. To evaluate the independent prognostic significance of CRP plasma levels, multivariate Cox regression models were applied.ResultsThe median follow-time was 80 months. Applying receiver operating characteristics (ROC) analysis, the optimal cut-off level for the plasma CRP was 8.6 mg l⁻¹. An elevated CRP level was associated with decreased CSS in univariate (hazard ratio (HR) 3.36, 95% confidence interval (CI) 1.42–7.91; p = 0.006) and multivariate analysis (HR 4.31, 95% CI 1.22–15.1; p = 0.023). Furthermore, a significant association with OS was detected in univariate (HR 2.69, 95% CI 1.57–4.59; p < 0.001) and multivariate analyses (HR 3.24, 95% CI 1.84–5.71, p < 0.001). Multivariate analysis also showed a significant association between plasma CRP and clinical DFS (HR 2.07, 95% CI 1.02–4.17; p = 0.043).ConclusionsIn the present study, an elevated plasma CRP (⩾8.6 mg l⁻¹) has been identified as a prognostic factor for poor CSS, OS and DFS in prostate cancer patients undergoing radiotherapy. The association between elevated CRP levels and poor prognosis was independent of other measures of prognosis such as tumour stage, Gleason grading and prostate specific antigen (PSA) level at diagnosis. If confirmed by additional studies, our findings may contribute to future individual risk assessment in prostate cancer patients.     

Role of cardioprotective therapy for prevention of cardiotoxicity with chemotherapy: A systematic review and meta-analysis

BackgroundCardiotoxicity is a well-recognised complication of chemotherapy with anthracycline and/or trastuzumab, and its prevention remains an important challenge in cancer survivorship. Several successful preventative strategies have been identified in animal trials. We sought to assemble the clinical evidence that prophylactic pharmacological interventions could prevent left ventricular (LV) dysfunction and heart failure in patients undergoing chemotherapy.MethodsWe undertook a systemic review of the evidence from randomised trials and observational studies where a prophylactic intervention was compared with a control arm in patients with a normal ejection fraction and no past history of heart failure. The primary outcome was development of heart failure (HF), a drop in ejection fraction (EF) or both. A random-effects model was used to combine relative risks (RR) and 95% confidence intervals (CIs), and a meta-regression was undertaken to assess the impact of potential covariates.FindingsData were collated from 14 published articles (n = 2015 paediatric and adult patients) comprising 12 randomised controlled trials and two observational studies. The most studied chemotherapeutic agents were anthracyclines, and prophylactic agents included dexrazoxane, statins, beta-blocker and angiotensin antagonists. There were 304 cardiac events in the control arm compared to 83 in the prophylaxis arm (RR = 0.31 [95% CI: 0.25–0.39], p < 0.00001). Cardiac events were reduced with dexrazoxane (RR = 0.35 [95% CI 0.27–0.45], p < 0.00001), beta-blockade (RR = 0.31 [95% CI 0.16–0.63], p = 0.001), statin (RR = 0.31 [95% CI 0.13–0.77], p = 0.01) and angiotensin antagonists (RR = 0.11 [95% CI 0.04–0.29], p < 0.0001).InterpretationProphylactic treatment with dexrazoxane, beta-blocker, statin or angiotensin antagonists appear to have similar efficacy for reducing cardiotoxicity.     

Low level of education is associated with later stage at diagnosis and reduced survival in cutaneous malignant melanoma: A nationwide population-based study in Sweden

BackgroundA worse outcome has been reported for cutaneous malignant melanoma (CMM) patients with low socioeconomic status. We have investigated the association between level of education, clinical stage at diagnosis (stage at diagnosis) and CMM-specific survival in Sweden.MethodsWe identified 27,235 patients from the Swedish Melanoma Register diagnosed with a primary invasive CMM between 1990 and 2007 and linked data to nationwide, population-based, health and census registers with a follow-up to 2010.ResultsThe odds ratio (OR) of higher disease stage at diagnosis was significantly increased in lower education groups (OR stage II versus I = 1.6; 95% confidence interval (CI) = 1.5–1.7. OR stage III–IV versus I = 2.3; 95% CI = 1.8–2.9). The risk of dying of CMM, was significantly increased in patients with low (hazard ratio (HR) low versus high = 2.02; 95% CI = 1.80–2.26; p < 0.0001) and intermediate (HR intermediate versus high = 1.35; 95% CI = 1.20–1.51; p < 0.0001) level of education. After adjustment for age, gender, stage at diagnosis and other known prognostic factors, the HRs remained significant for low versus high (HR = 1.13; 95% CI = 1.01–1.27; p = 0.04) but not for intermediate versus high (HR = 1.11; 95% CI = 0.99–1.24; p = 0.08) education. The HR associated with low level of education was significantly higher among female patients, patients <55 years, patients with truncal tumours and during the first 5 years after diagnosis.ConclusionLower level of education is associated with reduced CMM-specific survival, which may at least partially be attributed to a more advanced stage at diagnosis. These results emphasise the need for improved early detection strategies.     

Treatment of advanced hepatocellular carcinoma with long-acting octreotide: A phase III multicentre,randomised, double blind placebo-controlled study

BackgroundA previous study reported a significant survival benefit for octreotide compared with no treatment in patients with advanced hepatocellular carcinoma (HCC). This was investigated further in this multicentre study.Patients and methodsTwo hundred and seventy two patients with HCC who were ineligible for curative treatments or had relapsed following potentially curative therapies were randomised to receive long-acting octreotide, 30 mg as an intramuscular injection once every 4 weeks for up to 2 years, or placebo.ResultsAt the time of the final analysis, median overall survival (OS) was 6.53 months (95% confidence interval [CI], 4.8–8.3) for octreotide versus 7.03 months (95% CI, 5.43–8.53) for placebo (p = 0.34). Progression-free survival (p = 0.26) also did not differ significantly between the two treatment groups. No objective responses were achieved in the octreotide group but 33% of patients achieved disease stabilisation for a mean time of 5.5 months (95% CI, 1.1–9.9). The median time until definitive global health score deterioration (according to QLQ-C30) was 2.3 months (95% CI, 1.4–3.7) in the octreotide and 4 months (95% CI, 2.2–5.7) in the placebo group (p = 0.09). There were four objective responses in the placebo group. Octreotide was well tolerated; seven patients reported severe adverse events possibly related to octreotide and there were no cases of haematoma or cholecystitis.ConclusionsIn patients with advanced HCC, octreotide has a favourable safety profile but does not improve OS and could have a negative impact on quality of life.     

The incidence and relative risk of cardiovascular toxicity in patients treated with new hormonal agents for castration-resistant prostate cancer

AimNew hormonal agents are available for treating metastatic castration-resistant prostate cancer (mCRPC). We aim to define the incidence and relative risk (RR) of cardiovascular events in mCRPC patients treated with these agents.MethodsProspective studies were identified by searching the MEDLINE/PubMed, Cochrane Library and ASCO Meeting abstracts. Combined relative risks (RRs) and 95% confidence intervals (CIs) were calculated using fixed- or random-effects methods.ResultsWe included six articles in this meta-analysis covering a total of 6735 patients who were used to evaluate cardiac toxicity. The use of new hormonal agents was associated with an increased risk of all grades of such toxicity (RR = 1.32, 95% CI, 1.08–1.60; p = 0.006) compared to a placebo, even if the absolute difference in terms of incidence was small at 14.8% versus 11.5%, respectively. No increased risk of grade 3–4 events (RR = 1.35, 95% CI, 0.90–2.03; p = 0.15) was observed.A total of 7830 patients were used to evaluate hypertension, and it was found that the use of new hormonal agents compared to a placebo was associated with an increased risk of all-grades (RR = 1.84, 95% CI, 1.37–2.46; p < 0.001) and grade 3–4 events (RR = 1.77, 95% CI, 1.13–2.77; p = 0.01). The absolute incidence was 12.5% versus 7.5% for all-grades and 3.7% versus 2.4% for grade 3–4.ConclusionsThis analysis revealed a significant increase in the incidence and RR of cardiovascular toxicity in mCRPC treated with new hormonal agents as opposed to a placebo, even though the occurrence of all- and grade 3–4 events rose only 14% and 4%, respectively. Follow-ups for the onset of treatment-related cardiovascular events should therefore be considered in these patients.     

Predictors of the use of complementary and alternative medicine (CAM) by women at high risk for breast cancer

BackgroundFew data exist regarding the use of complementary and alternative medicine (CAM) by unaffected women at high risk of breast cancer.MethodsSelf-reported CAM use by women from multiple-case breast cancer families was obtained by questionnaire. Factors associated with CAM use were assessed using multiple logistic regression.ResultsOf 892 women, 55% (n = 489) used CAM, 6% (n = 53) specifically to prevent cancer. CAM use was independently associated with tertiary education level (OR 2.56, 95% CI 1.83–3.58, p < 0.001), greater physical activity (OR 1.05 per hour of physical activity/week, 95% CI 1.00–1.10, p = 0.049), greater anxiety (OR 1.92, 95% CI 1.16–3.16, p = 0.01), not currently smoking (OR 0.64, 95% CI 0.42–0.97, p = 0.037) and lower perceived BC risk (OR 0.82 per 20 percentage points, 95% CI 0.72–0.94, p = 0.005).ConclusionsThe majority of high-risk women use CAM, but mostly for reasons other than cancer prevention. Most predictors of CAM use are consistent with the limited literature for women at high risk for cancer.     

Platinum-based neoadjuvant chemotherapy in triple-negative breast cancer: a systematic review and meta-analysis

BackgroundThe role of platinum-based neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) patients is highly controversial and it is not endorsed by current guidelines. Our meta-analysis aimed to better elucidate its activity, efficacy and safety.Material and methodsA systematic search of Medline, Web of Science and conferences proceedings up to 30 October 2017 was carried out to identify randomized controlled trials (RCTs) investigating platinum-based versus platinum-free neoadjuvant chemotherapy in TNBC patients. Using the fixed and random effects models, pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CI) were calculated for pathological complete response (pCR, defined as ypT0/is pN0), event-free survival (EFS), overall survival (OS) and grade 3 and 4 adverse events (AEs: neutropenia, anemia, thrombocytopenia and neuropathy).ResultsNine RCTs (N = 2109) were included. Overall, platinum-based neoadjuvant chemotherapy significantly increased pCR rate from 37.0% to 52.1% (OR 1.96, 95% CI 1.46–2.62, P < 0.001). Platinum-based neoadjuvant chemotherapy remained significantly associated with increased pCR rate also after restricting the analysis to the three RCTs (N = 611) that used the same standard regimen in both groups of weekly paclitaxel (with or without carboplatin) followed by anthracycline and cyclophosphamide (OR 2.53, 95% CI 1.37–4.66, P = 0.003). Conversely, among the 96 BRCA-mutated patients included in two RCTs, the addition of carboplatin was not associated with significantly increased pCR rate (OR 1.17, 95% CI 0.51–2.67, P = 0.711). Two RCTs (N = 748) reported survival outcomes: no significant difference in EFS (HR 0.72, 95% CI 0.49–1.06, P = 0.094) and OS (HR 0.86, 95% CI 0.46–1.63, P = 0.651) was observed.A significant higher risk of grade 3 and 4 hematological AEs, with no increased risk of grade 3 and 4 neuropathy was observed with platinum-based neoadjuvant chemotherapy.ConclusionIn TNBC patients, platinum-based neoadjuvant chemotherapy is associated with significantly increased pCR rates at the cost of worse hematological toxicities. Platinum-based neoadjuvant chemotherapy may be considered an option in TNBC patients.PROSPERO registration numberCRD42018080042.     

Novel physical activity interventions for older patients with prostate cancer on hormone therapy: A pilot randomized study

BackgroundAndrogen deprivation therapy (ADT) can decrease the physical performance (PP) of older men with prostate cancer (PC).MethodsWe conducted a three-arm randomized pilot study (n = 19) comparing a home-based walking and resistance intervention (EXCAP) and a technology-mediated walking and resistance intervention using Wii-Fit to a usual-care arm in men ≥ 70 years with PC receiving ADT. The intervention lasted for 6 weeks, with follow-up at 12 weeks. The primary pre-specified outcome was change in Short Physical Performance Battery (SPPB) score. Mixed effects regression models were used to assess change in outcomes over time.ResultsMean participant age was 70 years (range: 67–93). Eight patients were randomized to the Wii-Fit arm, 6 to the EXCAP arm, and 5 to the usual-care arm. SPPB scores remained nearly constant in the usual-care arm (β = − 0.12; p = 0.79), while individuals in the EXCAP arm had on average a 1.2 point increase at each follow-up (β = 1.20; 95% CI: 0.36, 2.06). The Wii-fit arm had a non-significant increase in SPPB score over time relative to usual-care (β = 0.32; 95% CI − 0.43, 1.06; p = 0.46).Individuals in the EXCAP arm had an increase in steps per day over time compared to the usual-care arm (p-value = 0.006); the EXCAP arm had an increase of 2720 steps (95% CI: 1313, 4128) while the usual-care arm had an increase of 97 steps (95% CI: − 1140, 1333). Participants in the Wii-Fit arm had an increase of 1020 steps (95% CI: − 474, 1238, p = 0.710). Other outcomes (i.e., handgrip strength, lean muscle mass, and chest press repetitions) were not statistically significant.ConclusionsA home-based aerobic and resistance exercise program, EXCAP, shows promise for improving PP in older men with PC on ADT.     

First-line anthracycline-based chemotherapy for angiosarcoma and other soft tissue sarcoma subtypes: Pooled analysis of eleven European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group trials

BackgroundAngiosarcoma is a rare subtype of soft tissue sarcoma (STS). Doxorubicin is the standard first-line chemotherapy for advanced STS. It is not known whether angiosarcoma response to anthracycline-based chemotherapy is different to other STS subtypes.MethodsPooled data were analysed from 11 prospective randomised and non-randomised European Organisation for Research and Treatment of Cancer (EORTC) clinical trials of first-line anthracycline-based chemotherapy for advanced STS. Baseline patient characteristics, chemotherapy response, progression free survival (PFS) and overall survival (OS) of angiosarcoma patients were compared with other STS patients. Analysis was performed to identify factors prognostic for angiosarcoma response to chemotherapy, PFS and OS.ResultsWith a median follow-up of 4.2 years, data from 108 locally advanced and metastatic angiosarcoma patients and 2557 patients with other STS histologies were analysed. 25% of angiosarcoma patients had a complete or partial response to chemotherapy compared to 21% for other STS histotypes. The median PFS was 4.9 months and OS 9.9 months, which were not significantly different from other STS histotypes. In univariate analysis, bone metastases were an adverse prognostic factor for OS (hazard ratio (HR) 1.66, 95% confidence interval (CI) 1.03–2.67; p = 0.036). Tumour grade was as an adverse prognostic factor for PFS (HR 1.72, 95% CI 1.01–2.92; p = 0.044) and OS (HR 2.03; 95% CI 1.16–3.56; p = 0.011). Compared to single agent anthracyclines, doxorubicin + ifosfamide was associated with improved PFS (HR 0.53, 95% CI 0.33–0.86; p = 0.010) and OS (HR 0.53, 95% CI 0.32–0.90; p = 0.018).ConclusionsAngiosarcoma response and survival following first-line anthracycline-based chemotherapy was similar to other STS histotypes. Our analysis provides a useful measure of angiosarcoma response to chemotherapy for comparison with future clinical trials.     

Posttraumatic stress,depression and anxiety among adult long-term survivors of cancer in adolescence

BackgroundTo determine the prevalence of posttraumatic stress, depression and anxiety in adults who have survived cancer (?5 years) diagnosed in adolescence, as compared to healthy controls.Patients and methodsSurvivors (n = 820) of cancer during adolescence (age M = 30.4 ± 6.0 years; M = 13.7 ± 6.0 years since diagnosis) and 1027 matched controls without history of cancer (age M = 31.5 ± 6.9 years) completed standardised questionnaires measuring posttraumatic stress, depression and anxiety. Additionally, sub-groups of 202 survivors and 140 controls with elevated scores received structured interviews to ascertain DSM-IV-diagnoses.ResultsA total of 22.4% of the survivors reported clinically relevant symptoms of posttraumatic stress, anxiety and/or depression compared to 14.0% of the controls (odds ratios [ORs] 1.77; 95% confidence interval [CI] 1.39–2.26). The odds of posttraumatic stress symptoms in male (OR 3.92, 95% CI 1.80–8.51) and female (OR 3.83, 95% CI 2.54–5.76) survivors were more than three times those in the controls. However, only female survivors reported symptoms of depression and anxiety significantly more often (respectively: OR 2.12, 95% CI 1.16–3.85; and OR 1.86, 95% CI 1.33–2.59) than the controls. A relevant subgroup of 24.3% of the survivors met DSM-IV criteria for at least one mental disorder compared to 15.3% of the controls.ConclusionSurvivors of cancer during adolescence show an elevated risk of presenting symptoms of posttraumatic stress, anxiety and/or depression during adulthood which is also reflected in a greater number of DSM-IV diagnoses when compared to controls. Comprehensive follow-up assessments should include the examination of possible psychological late effects of a cancer diagnosis in adolescence in order to identify survivors needing psychosocial interventions even years after the completion of successful medical treatment.