Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations.

Cancer and cardiovascular (CV) disease are the most prevalent diseases in the developed world. Evidence increasingly shows that these conditions are interlinked through common risk factors, coincident in an ageing population, and are connected biologically through some deleterious effects of anticancer treatment on CV health. Anticancer therapies can cause a wide spectrum of short- and long-term cardiotoxic effects. An explosion of novel cancer therapies has revolutionised this field and dramatically altered cancer prognosis. Nevertheless, these new therapies have introduced unexpected CV complications beyond heart failure. Common CV toxicities related to cancer therapy are defined, along with suggested strategies for prevention, detection and treatment. This ESMO consensus article proposes to define CV toxicities related to cancer or its therapies and provide guidance regarding prevention, screening, monitoring and treatment of CV toxicity. The majority of anticancer therapies are associated with some CV toxicity, ranging from asymptomatic and transient to more clinically significant and long-lasting cardiac events. It is critical however, that concerns about potential CV damage resulting from anticancer therapies should be weighed against the potential benefits of cancer therapy, including benefits in overall survival. CV disease in patients with cancer is complex and treatment needs to be individualised. The scope of cardio-oncology is wide and includes prevention, detection, monitoring and treatment of CV toxicity related to cancer therapy, and also ensuring the safe development of future novel cancer treatments that minimise the impact on CV health. It is anticipated that the management strategies discussed herein will be suitable for the majority of patients. Nonetheless, the clinical judgment of physicians remains extremely important; hence, when using these best clinical practices to inform treatment options and decisions, practitioners should also consider the individual circumstances of their patients on a case-by-case basis.

Autologous stem-cell transplantation after second-line brentuximab vedotin in relapsed or refractory Hodgkin lymphoma.

Background: We previously demonstrated that brentuximab vedotin (BV) used as second-line therapy in patients with Hodgkin lymphoma is a tolerable and effective bridge to autologous hematopoietic cell transplantation (AHCT). Here, we report the post-AHCT outcomes of patients treated with second-line standard/fixed-dose BV and an additional cohort of patients where positron-emission tomography adapted dose-escalation of second-line BV was utilized. Patients and methods: Patients on the dose-escalation cohort received 1.8 mg/kg of BV intravenously every 3 weeks for two cycles. Patients in complete remission (CR) after two cycles received two additional cycles of BV at 1.8 mg/kg, while patients with stable disease or partial response were escalated to 2.4 mg/kg for two cycles. All patients, regardless of treatment cohort, proceeded directly to AHCT or received additional pre-AHCT therapy at the discretion of the treating physician based on remission status after second-line BV. Results: Of the 20 patients enrolled to the BV dose-escalation cohort, 8 patients underwent BV dose-escalation. BV escalation was well-tolerated, but no patients who were escalated converted to CR. Of 56 evaluable patients treated across cohorts, the overall response rate (ORR) to second-line BV was 75% with 43% CR. Twenty-eight (50%) patients proceeded directly to AHCT without post-BV chemotherapy, and a total of 50 patients proceeded to AHCT. Thirteen patients received consolidative post-AHCT therapy with either radiation, BV, or a PD-1 inhibitor. After AHCT, the 2-year progression-free survival (PFS) and overall survival were 67% and 93%, respectively. The 2-year PFS among patients in CR at the time of AHCT (n = 37) was 71% compared with 54% in patients not in CR (p = 0.12). The 2-year PFS in patients who proceeded to AHCT directly after receiving BV alone was 77%. Conclusions: Second-line BV is an effective bridge to AHCT that produces responses of sufficient depth to provide durable remission in conjunction with AHCT (clinicaltrials.gov: NCT01393717).

Conditional survival and cause-specific mortality after autologous hematopoietic cell transplantation for hematological malignancies.

The probability of survival is conventionally calculated from autologous hematopoietic cell transplantation (aHCT). Conditional survival takes into account the changing probability of survival with time survived, but this is not known for aHCT populations. We determined disease- and cause-specific conditional survival for 2388 patients treated with aHCT over a period of 20 years at a single institution. A total of 1054 deaths (44% of the cohort) were observed: 78% attributed to recurrent disease; 9% to subsequent malignancies and 6% to cardiopulmonary disease. Estimated probability of relative survival was 62% at 5 years and 50% at 10 years from aHCT. On the other hand, the 5-year relative survival was 70, 75, 81 and 88% after having survived 1, 2, 5 and 10 years after aHCT, respectively. The cohort was at a 13.9-fold increased risk of death compared with the general population (95% confidence interval (CI)=13.1-14.8). The risk of death approached that of the general population for 10-year survivors (standardized mortality ratio (SMR)=1.4, 95% CI=0.9-1.9), with the exception of female Hodgkin's lymphoma patients transplanted before 1995 at age 40 years (SMR=6.0, 95% CI=1.9-14.0). Among those who had survived 10 years, nonrelapse-related mortality rates exceeded relapse-related mortality rates. This study provides clinically relevant survival estimates after aHCT, and helps inform interventional strategies.

Health behaviors and cancer screening practices in long-term survivors of hematopoietic cell transplantation (HCT): a report from the BMT Survivor Study.

Patients undergoing hematopoietic cell transplantation (HCT) are at increased risk of chronic health conditions, including second malignant neoplasms and cardiovascular disease. Little is known about health behaviors and cancer screening practices among HCT survivors that could moderate the risk of these conditions. The BM transplant survivor study examined health behaviors and cancer screening practices in individuals who underwent HCT between 1976 and 1998, and survived 2+ years. Health behavior was deemed as high risk, if an individual was a current smoker and if they reported risky alcohol intake (≥4 drinks per day (males), ≥3 drinks per day (females)) on days of alcohol consumption. Cancer screening assessment was per American Cancer Society recommendations. There were 1040 survivors: 42.7% underwent allogeneic HCT; 43.8% were female; median time from HCT: 7.4 years (range 2.0-27.7 years). Median age at study participation: 43.8 years (range 18.3-73.0 years). Multivariate regression analysis revealed younger age (<35 years) at study participation (Odds ratio (OR)=4.7; P<0.01) and lower education (

Painless urethral bleeding: an unusual presentation of Von Willebrand disease.

Von Willebrand disease (vWD) is the most common bleeding disorder, and usually presents with either easy bruising or mucus membrane bleeding. Many patients are also diagnosed as a result of abnormal pre-operative laboratory tests. In this report, we describe two patients presenting with painless, persistent urethral bleeding as their initial manifestation of vWD. The first patient began bleeding after a Foley catheter was placed during a hospital admission for status epilepticus. A urologic examination demonstrated a wound in the posterior urethra. Despite repeated attempts at controlling the bleeding with cautery, the bleeding persisted. The second patient presented with spontaneous urethral bleeding and a normal urologic examination. Due to persistent bleeding, both patients underwent a coagulation evaluation that demonstrated the presence of type 1 vWD. The first patient had resolution of his bleeding following 5 weeks of Alphanate, a von Willebrand factor containing factor VIII concentrate, and aminocaproic acid. The second patient initially responded to desmopressin, but subsequently required Humate-P to achieve complete resolution. These cases illustrate the importance of an evaluation for bleeding disorders in patients with persistent bleeding from any site.

Predictors of discharges against medical advice from a short-term hospital detoxification unit.

The primary goal of this study was to identify factors associated with patients leaving a 3-day hospital detoxification unit against medical advice (AMA). Medical records of 302 patients who were admitted for alcohol or other drug withdrawal were reviewed. Variables examined were: demographics, reported history of drug use, urine toxicology at admission, medication received during the detoxification, and admission day. Data were analyzed using a case-control design. Logistic regression was used to identify independent predictors. We found that being younger, having a shorter history of cocaine abuse, being admitted on a Friday and being an opiate dependent patient treated with clonidine only during the detoxification, were significantly associated with leaving AMA. These findings may provide information that can help clinicians identify those patients who are most at risk for leaving AMA. This will in turn allow them the opportunity to initiate preventive measures to decrease unnecessary attrition and improve utilisation of treatment resources.

Widowhood and mortality in an Armenian church parish in Lebanon.

A nonconcurrent cohort study was conducted in Lebanon by using the parish records of an Armenian Apostolic Orthodox church. Included in the study were 1,529 married couples. The observation period extended from 1949-1980 with follow-up information available on 90% of the subjects based on a review of burial registers, parish census records, and neighborhood inquiries. Identified during the observation period were 152 widowers and 623 widows. Three analytic procedures were used to compare the mortality of widowed to married subjects: person-years, matched-pair, and life table analyses. The results showed an increased risk of mortality for widowed compared with married subjects, although this excess in risk was not overall statistically significant. Most important was the result that among widowers as opposed to widows the higher risk of mortality acted at approximately ages 66-75 years. The suggested hypotheses to explain this finding include changes in the network size as well as social support systems which act in a particular way in this culture for men at the age of retirement. The results of this initial study of a specific community in a Middle Eastern society parallel findings in studies of Western industrial societies; they also tend to give additional evidence for the association of increased risk when widowhood is accompanied by increased stress caused by other life changes such as retirement.