American Society of Clinical Oncology Clinical Evidence Review on the Ongoing Care of Adult Cancer Survivors: Cardiac and Pulmonary Late Effects

Carver, Joseph R.; Shapiro, Charles L.; Ng, Andrea K.; Jacobs, Linda A.; Schwartz, Cindy L.; Virgo, Katherine S.; Hagerty, Karen L.; Somerfield, Mark R.; Vaughn, David J.

doi:10.1200/jco.2007.10.9777

Cited by 710 publications

(534 citation statements)

References 105 publications

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“…It manifests in several forms, ranging from acute arrhythmias and nonspecific electrocardiogram changes to decreases in LVEF. Beside age, hypertension, diabetes and coronary heart disease, trastuzumab treatment represents a significant risk factor for the development of anthracycline related cardiotoxicity [12,18]. The most severe complication is cardiomyopathy leading potentially to a permanent cardiac damage [20].…”

Section: Discussionmentioning

confidence: 99%

“…This risk appears to be higher in patients receiving concurrent anthracyclines [29]. Slamon et al [12] 123 [30]. However, natural history of trastuzumab related cardiotoxicity differs significantly from the anthracycline induced one.…”

Section: Discussionmentioning

confidence: 99%

“…Reviewing the actual literature, independent risk factors for anthraycline and trastuzumab associated cardiac toxicity include age ([65 years), obesity ([27 kg/m 2 ), hypertension, hypercholesterolemia, preexisting cardiac diseases (incl. borderline LVEF) and diabetes mellitus [12].…”

Section: Introductionmentioning

confidence: 99%

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Pegylated liposomal doxorubicin and trastuzumab as 1st and 2nd line therapy in her2/neu positive metastatic breast cancer: a multicenter phase II trial

Stickeler¹,

Klar²,

Watermann³

et al. 2009

Breast Cancer Res Treat

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The combination therapy of doxorubicin and trastuzumab has been proven to be highly effective for metastatic breast cancer (MBC) patients with Her2/neu over-expressing tumors. However, this regimen is characterized by frequent cardiac toxicity, occurring in 27% of all treated patients and aggravating when the two substances are given concurrently. Pegylated liposomal doxorubicin (PLD) as a single agent reduces significantly cardiac toxicity and maintains efficacy compared to conventional doxorubicin. This prospective open labeled, multicenter phase II study assessed the potential cardiotoxicity and efficacy of PLD and trastuzumab as first and second line combination therapy in Her2/neu over-expressing MBC patients. Patients with Her2 over-expressing, measurable MBC with a baseline left ventricular ejection fraction (LVEF) C50% were treated with PLD 40 mg/m 2 every 4 weeks for 6 up to 9 cycles and weekly trastuzumab (4 mg/kg loading dose, then 2 mg/kg). Cardiotoxicity was defined as the appearance of clinical signs or symptoms of congestive heart failure in combination with a decrease in LVEF B44% or C10 units below the normal value of 50% in the obligatory, subsequently performed transthoracic echocardiography. Due to conflicting interests, the planned accrual goal of 30 patients was not reached. Finally 16 patients were enrolled. Ten patients presented with more than one metastatic site and six of them were in second-line therapy. The median LVEF in the study cohort was 66.1 ± 8.68% at baseline, 62.7 ± 5.11% after 6 cycles of therapy, 64.4 ± 7.61% at the first follow up and did not change significantly (61.0 ± 5.56% even at the 5th followup). Six out of 12 assessable patients (50.0%) demonstrated a clinical benefit and after a median follow-up of 15.4 months a median progression free survival of 9.67 and a median overall survival of 16.23 months. Non-cardiac side effects were mild with only 3 CTC grade 3 events of 247 treatment cycles (1.2%) and no grade 4 toxicities. The combination of PLD and trastuzumab in patients with Her2/neu over-expressing metastatic breast cancer is a safe, feasible and effective therapy. However, cardiac function should be monitored at close intervals. Due to the promising clinical response rates and mild toxicity profile in this prognostically unfavorable group, this combination therapy should be evaluated in larger studies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Pegylated liposomal doxorubicin and trastuzumab as 1st and 2nd line therapy in her2/neu positive metastatic breast cancer: a multicenter phase II trial

Stickeler¹,

Klar²,

Watermann³

et al. 2009

Breast Cancer Res Treat

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“…5 Recently, a large review of literature on the retrospective study performed and the surveillance of adult cancer survivors were presented with special focus on cardiac and pulmonary side effects. 24 The review concluded that the incidence of radiotherapy-induced cardiac side effects was in the range of 10-30%. The panel also concluded that very few prospective studies have been performed that investigates the advantage of surveillance in HL survivors.…”

Section: Discussionmentioning

confidence: 99%

“…They expressed a need for more prospective studies of cardiovascular prevention. 24 Diabetes mellitus, hypertension, hypercholesterolemia, first degree relative with CVD, history of antracycline therapy, obesity, physical inactivity and smoking are likely to act in concert with radiotherapy to the heart, coronary arteries and carotid arteries. These factors might increase risk of CVD in this patient cohort.…”

Section: Discussionmentioning

confidence: 99%

Long‐term risk of cardiovascular disease in Hodgkin lymphoma survivors—Retrospective cohort analyses and a concept for prospective intervention

Andersson

Näslund

Tavelin

et al. 2009

Intl Journal of Cancer

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Previous studies have shown increased cardiovascular mortality as late side effects in Hodgkin lymphoma (HL) patients. This study identifies stratifying risk factors for surveillance and defines concepts for a clinical feasible and noninvasive prospective protocol for intervention of cardiovascular side effects. HL patients diagnosed between 1965 and 1995 (n 5 6.946) and their first-degree relatives (FDR) were identified through the Swedish Cancer Registry and the Swedish Multigeneration Registry. For the HL and FDR cohort, in-patient care for cardiovascular disease (CVD) was registered through the Hospital Discharge Registry, Sweden. Standard incidence ratios of developing CVD for the HL cohort were calculated. A markedly increased risk for in-patient care of CVD was observed in HL patients with HL diagnosed at age 40 years or younger and with more than 10 years follow-up. In the HL survivors, a family history of congestive heart failure (CHF) and coronary artery disease (CAD) increased the risk for these diseases. The Swedish Hodgkin Intervention and Prevention study started in 2007. In the pilot feasibility study for prospective intervention (47 patients), about 25% of the cases had side effects and laboratory abnormalities. These patients were referred to a cardiologist or general practitioner. In the prospective cohort, a positive family history for CHF or CAD could be a stratifying risk factor when setting up a surveillance model. The prospective on-going study presents an intervention model that screens and treats for comorbidity factors. This article also presents an overview of the study concept.

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Long-term Somatic Disease Risk in Adult Danish Cancer Survivors

et al. 2019

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IMPORTANCE Long-term health effects of cancer in adult survivors are a major concern; however, it is difficult to differentiate between the consequences of cancer and cancer treatment and those of normal aging or comorbidity. OBJECTIVES To provide an overview and investigate the temporal pattern of hospitalizations for medically verified incident somatic disease in adult survivors compared with cancer-free comparison people, taking into consideration pretreatment comorbidity and the socioeconomic position of the participants. DESIGN, SETTING, AND PARTICIPANTS In this nationwide, population-based cohort-cohort study, 458 646 survivors of the 12 most frequent first primary cancers listed in the Danish Cancer Registry between January 1, 1997, and December 31, 2014, and 2 121 567 matched cancer-free comparison people were identified from the Danish Central Population Registry. Hospitalizations for somatic diseases after cancer diagnosis or study entry were identified from the National Patient Register and stratified according to the 11 main diagnostic groups in the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. A cohort of cancer survivors was formed for each combination of cancer type and diagnostic group, with a corresponding group of cancer-free people, resulting in 132 unique cohorts. Data analysis was performed from September 1, 2017, to January 15, 2018. MAIN OUTCOMES AND MEASURES Risk of hospitalization and the temporal pattern of incidence were analyzed in Cox proportional hazards regression models. Cumulative incidence proportions were calculated by the pseudo-observation method. RESULTS A total of 2 580 213 people were investigated, of whom 458 646 were cancer survivors (mean [SD] age, 69 [11.6] years; 230 793 [50.3%] male and 227 853 [49.7%] female) and 2 121 567 were comparison people (mean [SD] age, 69 [11.5] years; 1 054 465 [49.7%] male and 1 067 102 [50.3%] female). More cancer survivors vs comparison people had comorbid conditions at the time of cancer diagnosis or study entry (Charlson Comorbidity Index Ն1: 19% vs 13%). Overall, the risk of hospitalizations for somatic diseases was significantly higher for cancer survivors in almost all diagnostic groups (eg, diseases in the nervous system among breast cancer survivors: hazard ratio, 1.20; 95% CI, 1.17-1.22; diseases in the respiratory system in lung cancer survivors: hazard ratio, 5.85; 95% CI, 5.63-6.07; and diseases in blood and blood-forming organs in prostate cancer survivors: hazard ratio, 2.60; 95% CI, 2.50-2.71). CONCLUSIONS AND RELEVANCE The findings suggest that adult survivors of the 12 most common cancers are at significantly higher risk for a broad range of somatic diseases that require hospitalization compared with matched cancer-free comparison people. The results of this study suggest the importance of close, targeted monitoring for new somatic disease during follow-up care of cancer survivors.

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American Society of Clinical Oncology Clinical Evidence Review on the Ongoing Care of Adult Cancer Survivors: Cardiac and Pulmonary Late Effects

Abstract: An increased incidence of cardiac and/or pulmonary dysfunction is observed in cancer survivors. Research is needed to identify high-risk patients, and to determine the optimal screening strategies and subsequent treatment.

Cited by 710 publications

References 105 publications

Pegylated liposomal doxorubicin and trastuzumab as 1st and 2nd line therapy in her2/neu positive metastatic breast cancer: a multicenter phase II trial

Pegylated liposomal doxorubicin and trastuzumab as 1st and 2nd line therapy in her2/neu positive metastatic breast cancer: a multicenter phase II trial

Long‐term risk of cardiovascular disease in Hodgkin lymphoma survivors—Retrospective cohort analyses and a concept for prospective intervention

Long-term Somatic Disease Risk in Adult Danish Cancer Survivors

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