Morbidity In Cancer Survivors Research Articles

Comparison of bolus administration and short-term infusion versus long-term infusion of doxorubicin in terms of cardiotoxicity and efficacy.

Cardiotoxicity caused by anthracyclines chemotherapy is one of the leading causes of mortality and morbidity in cancer survivors. Continuous infusion (CI) instead of bolus (BOL) injection is one of the methods that seem to be effective in reducing doxorubicin (DOX) cardiotoxicity. Due to the variety of results, we decided to compare these two approaches regarding toxicity and efficacy and report the final results for different cancers. We included 21 studies (four preclinical and seventeen clinical trials) up to May 15, 2023. In children with acute lymphoblastic leukemia (ALL) and adults with chronic lymphoblastic leukemia (CLL) and gastric cancer, results were in favor of BOL injection, without increase in cardiotoxicity. On the other hand, CI showed to be better option in patients with small-cell lung cancer (SCLC) and breast cancer. Various results were also observed in adult patients with sarcoma. Overall, it can be concluded that the benefits of CI, especially in adults, outweigh its disadvantages. However, due to the variety of results and heterogeneity of studies, further clinical trials with a larger sample size and a longer duration of follow-up are needed to make a more accurate comparison between CI and BOL injection.

Abstract 15504: Impaired Branched-Chain Amino Acid Catabolism is Associated With Chemotherapy-Induced Heart Failure and Rescued by Metformin

Introduction: Heart failure resulting from cancer therapies represents a major cause of morbidity in cancer survivors. Interventional strategies to prevent and treat heart dysfunction in cardio-oncology patients continue to remain a challenge. Hypothesis: We posit that Branched-Chain Amino Acid Catabolism (BCAA) catabolism dysfunction is a likely causal mechanistic pathway in the pathogenesis of CTHF. Methods: In this study, we leveraged electronic health records , human-induced pluripotent stem cell ( iPSC )-derived cardiomyocyte model-based mechanistic studies, murine models, and network medicine-basedtranscriptomics analytic methodologies, to suggest that rescuing BCAA catabolic dysfunction is a promising approach for managing chemotherapy-induced heart failure, using doxorubicin as a prototypical example. Results: In our large-scale cardio-oncology cohort, we observed a significant incidence of heart dysfunction and abnormal NT-proBNP levels among patients treated with doxorubicin. Using murine heart failure models, we identified significant correlations between the abundance of branched-chain amino acids (isoleucine, leucine, and valine) and cardiac dysfunction after doxorubicin exposure. Mechanistic observations in human-induced pluripotent stem cell (iPSC)-derived cardiomyocyte models further support impaired branched-chain amino acid (BCAA) catabolism by doxorubicin. Through metabolite-enzyme network analysis, we identified metformin as a repurposable drug capable of restoring branched-chain amino acid catabolism, thereby improving mitochondrial function. Human iPSC-based mechanistic studies revealed that metformin combined with doxorubicin resulted in improved insulin signaling, endothelial cell reprogramming, increased RARA gene expression (a key doxorubicin-induced heart failure GWAS gene) and reduced pro-fibrotic signaling. Furthermore, we demonstrate that metformin improved murine cardiac function following doxorubicin exposure. Conclusions: Our findings utilized electronic health records, iPSC-based mechanistic studies, and murine models to suggest that BCAA catabolic dysfunction may be a promising approach for managing chemotherapy-induced heart failure.

Cardio-Oncology Rehabilitation for Cancer Survivors With High Cardiovascular Risk

Cardiovascular disease is a leading cause of morbidity in cancer survivors, which makes strategies aimed at mitigating cardiovascular risk a subject of major contemporary importance. To assess whether a center-based cardiac rehabilitation (CBCR) framework compared with usual care encompassing community-based exercise training (CBET) is superior for cardiorespiratory fitness improvement and cardiovascular risk factor control among cancer survivors with high cardiovascular risk. This prospective, single-center, randomized clinical trial (CORE trial) included adult cancer survivors who had exposure to cardiotoxic cancer treatment and/or previous cardiovascular disease. Enrollment took place from March 1, 2021, to March 31, 2022. End points were assessed at baseline and after the 8-week intervention. Participants were randomly assigned in a 1:1 ratio to 8 weeks of CBCR or CBET. The combined aerobic and resistance exercise sessions were performed twice a week. The powered primary efficacy measure was change in peak oxygen consumption (V̇o2) at 2 months. Secondary outcomes included handgrip maximal strength, functional performance, blood pressure (BP), body composition, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), lipid profile, plasma biomarker levels, physical activity (PA) levels, psychological distress, quality of life (QOL), and health literacy. A total of 75 participants completed the study (mean [SD] age, 53.6 [12.3] years; 58 [77.3%] female), with 38 in the CBCR group and 37 in the CBET group. Participants in CBCR achieved a greater mean (SD) increase in peak V̇o2 than those in CBET (2.1 [2.8] mL/kg/min vs 0.8 [2.5] mL/kg/min), with a between-group mean difference of 1.3 mL/kg/min (95% CI, 0.1-2.6 mL/kg/min; P = .03). Compared with the CBET group, the CBCR group also attained a greater mean (SD) reduction in systolic BP (-12.3 [11.8] mm Hg vs -1.9 [12.9] mm Hg; P < .001), diastolic BP (-5.0 [5.7] mm Hg vs -0.5 [7.0] mm Hg; P = .003), and BMI (-1.2 [0.9] vs 0.2 [0.7]; P < .001) and greater mean (SD) improvements in PA levels (1035.2 [735.7] metabolic equivalents [METs]/min/wk vs 34.1 [424.4] METs/min/wk; P < .001), QOL (14.0 [10.0] points vs 0.4 [12.9] points; P < .001), and health literacy scores (2.7 [1.6] points vs 0.1 [1.4] points; P < .001). Exercise adherence was significantly higher in the CBCR group than in the CBET group (mean [SD] sessions completed, 90.3% [11.8%] vs 68.4% [22.1%]; P < .001). The CORE trial showed that a cardio-oncology rehabilitation model among cancer survivors with high cardiovascular risk was associated with greater improvements in peak V̇o2 compared with usual care encompassing an exercise intervention in a community setting. The CBCR also showed superior results in exercise adherence, cardiovascular risk factor control, QOL, and health literacy. ClinicalTrials.gov Identifier: NCT05132998.

Evolving data on cardiovascular complications in cancer

Cancer and cardiovascular disease are leading causes of mortality and morbidity worldwide. Scientific studies show that patients with cancer are at increased risk of developing cardiovascular events, leading to the novel cardio-oncology research field. Growing evidence suggests that cancer and cardiovascular disease are not separate entities but are connected through shared risk factors, pathological mechanisms, and genetic predispositions. Moreover, anticancer therapies such as radiotherapy have been known to further increase the cardiovascular risk in patients with cancer. Due to the significant advances in oncological diagnostics and therapy, the number of cancer survivors has been growing substantially. Nowadays, the majority of patients with cancer dies from non-cancer causes. Cardiovascular disease substantially contributes to mortality and morbidity in cancer survivors. For some cancers, such as breast, prostate, endometrial and thyroid cancer, about half of the patients dies from cardiovascular disease. This raises an urge for effective strategies in preventing and treating cardiovascular events in patients living with and surviving cancer. In this review, we address the evolving data on cardiovascular disease in patients with cancer, with a special focus on atherothrombotic manifestations including myocardial infarction and ischemic stroke.

Cardiac risk stratification in cancer patients: A longitudinal patient-patient network analysis.

Cardiovascular disease is a leading cause of death in general population and the second leading cause of mortality and morbidity in cancer survivors after recurrent malignancy in the United States. The growing awareness of cancer therapy-related cardiac dysfunction (CTRCD) has led to an emerging field of cardio-oncology; yet, there is limited knowledge on how to predict which patients will experience adverse cardiac outcomes. We aimed to perform unbiased cardiac risk stratification for cancer patients using our large-scale, institutional electronic medical records. We built a large longitudinal (up to 22 years' follow-up from March 1997 to January 2019) cardio-oncology cohort having 4,632 cancer patients in Cleveland Clinic with 5 diagnosed cardiac outcomes: atrial fibrillation, coronary artery disease, heart failure, myocardial infarction, and stroke. The entire population includes 84% white Americans and 11% black Americans, and 59% females versus 41% males, with median age of 63 (interquartile range [IQR]: 54 to 71) years old. We utilized a topology-based K-means clustering approach for unbiased patient-patient network analyses of data from general demographics, echocardiogram (over 25,000), lab testing, and cardiac factors (cardiac). We performed hazard ratio (HR) and Kaplan-Meier analyses to identify clinically actionable variables. All confounding factors were adjusted by Cox regression models. We performed random-split and time-split training-test validation for our model. We identified 4 clinically relevant subgroups that are significantly correlated with incidence of cardiac outcomes and mortality. Among the 4 subgroups, subgroup I (n = 625) has the highest risk of de novo CTRCD (28%) with an HR of 3.05 (95% confidence interval (CI) 2.51 to 3.72). Patients in subgroup IV (n = 1,250) had the worst survival probability (HR 4.32, 95% CI 3.82 to 4.88). From longitudinal patient-patient network analyses, the patients in subgroup I had a higher percentage of de novo CTRCD and a worse mortality within 5 years after the initiation of cancer therapies compared to long-time exposure (6 to 20 years). Using clinical variable network analyses, we identified that serum levels of NT-proB-type Natriuretic Peptide (NT-proBNP) and Troponin T are significantly correlated with patient's mortality (NT-proBNP > 900 pg/mL versus NT-proBNP = 0 to 125 pg/mL, HR = 2.95, 95% CI 2.28 to 3.82, p < 0.001; Troponin T > 0.05 μg/L versus Troponin T ≤ 0.01 μg/L, HR = 2.08, 95% CI 1.83 to 2.34, p < 0.001). Study limitations include lack of independent cardio-oncology cohorts from different healthcare systems to evaluate the generalizability of the models. Meanwhile, the confounding factors, such as multiple medication usages, may influence the findings. In this study, we demonstrated that the patient-patient network clustering methodology is clinically intuitive, and it allows more rapid identification of cancer survivors that are at greater risk of cardiac dysfunction. We believed that this study holds great promise for identifying novel cardiac risk subgroups and clinically actionable variables for the development of precision cardio-oncology.

Exercise Improves Cancer-free Survival and Health Span in a Model of Radiation-induced Cancer.

Radiation therapy increases the risk of secondary malignancy and morbidity in cancer survivors. The role of obesity and exercise training in modulating this risk is not well understood. As such, we used a preclinical model of radiation-induced malignancy to investigate whether diet-induced obesity and/or endurance exercise training altered lifelong survival, cancer incidence, and morbidity. Male CBA mice were randomly divided into control diet/sedentary group (CTRL/SED), high-fat diet (45% fat)/sedentary group (HFD/SED), control diet/exercise group (2-3 d·wk-1; CTRL/EX), or high-fat diet/exercise group (HFD/EX) groups then exposed to whole-body radiation (3 Gy). End point monitoring and pathology determined mortality and cancer incidence, respectively. Health span index, a measure of morbidity, was determined by a composite measure of 10 anthropometric, metabolic, performance, and behavioral measures. Overall survival was higher in HFD/SED compared with CTRL/SED (P < 0.05). The risk of cancer-related mortality by 18 months postradiation was 1.99 and 1.63 in HFD/SED compared with CTRL/EX (RR = 1.99, 95% confidence interval = 1.20-3.31, P = 0.0081) and CTRL/SED (RR = 1.63, 95% confidence interval = 1.06-2.49, P = 0.0250), respectively. The number of mice at end point with cancer was higher in HFD/SED compared with CTRL/EX and CTRL/SED (P < 0.05). Health span index was highest in CTRL/EX (score = +2.5), followed by HFD/EX (score = +1), and HFD/SED (score = -1) relative to CTRL/SED. This work provides the basis for future preclinical studies investigating the dose-response relationship between exercise training and late effects of radiation therapy as well as the mechanisms responsible for these effects.

Chemotherapy-induced acute vascular injury involves intracellular generation of ROS via activation of the acid sphingomyelinase pathway

Several categories of chemotherapy confer substantial risk for late-term vascular morbidity and mortality. In the present study, we aimed to investigate the mechanism of acute chemotherapy-induced vascular injury in normal tissues. Specifically, we looked at activation of the acid sphingomyelinase (ASMase)/ceramide pathway, which leads to generation of reactive oxygen species (ROS) and induction of oxidative stress that may result in vascular injury.In particular, we focused on two distinct drugs, doxorubicin (DOX) and cisplatin (CIS) and their effects on normal endothelial cells. In vitro, DOX resulted in increased ASMase activity, intra-cellular ROS production and induction of apoptosis. CIS treatment generated significantly reduced effects in endothelial cells. In-vivo, murine femoral arterial blood flow was measured in real-time, during and after DOX or CIS administration, using fluorescence optical imaging system. While DOX caused constriction of small vessels and disintegration of large vessels' wall, CIS induced minor vascular changes in arterial blood flow, correlating with the in vitro findings. These results demonstrate that DOX induces acute vascular injury by increased ROS production, via activation of ASMase/ceramide pathway, while CIS increases ROS production and its immediate extracellular translocation, without causing detectable acute vascular injury. Our findings may potentially lead to the development of new strategies to prevent long-term cardiovascular morbidity in cancer survivors.

The Utility of Cardiac Reserve for the Early Detection of Cancer Treatment-Related Cardiac Dysfunction: A Comprehensive Overview.

With progressive advancements in cancer detection and treatment, cancer-specific survival has improved dramatically over the past decades. Consequently, long-term health outcomes are increasingly defined by comorbidities such as cardiovascular disease. Importantly, a number of well-established and emerging cancer treatments have been associated with varying degrees of cardiovascular injury that may not emerge until years following the completion of cancer treatment. Of particular concern is the development of cancer treatment related cardiac dysfunction (CTRCD) which is associated with an increased risk of heart failure and high risk of morbidity and mortality. Early detection of CTRCD appears critical for preventing long-term cardiovascular morbidity in cancer survivors. However, current clinical standards for the identification of CTRCD rely on assessments of cardiac function in the resting state. This provides incomplete information about the heart's reserve capacity and may reduce the sensitivity for detecting sub-clinical myocardial injury. Advances in non-invasive imaging techniques have enabled cardiac function to be quantified during exercise thereby providing a novel means of identifying early cardiac dysfunction that has proved useful in several cardiovascular pathologies. The purpose of this narrative review is (1) to discuss the different non-invasive imaging techniques that can be used for quantifying different aspects of cardiac reserve; (2) discuss the findings from studies of cancer patients that have measured cardiac reserve as a marker of CTRCD; and (3) highlight the future directions important knowledge gaps that need to be addressed for cardiac reserve to be effectively integrated into routine monitoring for cancer patients exposed to cardiotoxic therapies.

Metabolic Imaging in Cardio-oncology.

Tremendous progress in cancer detection and therapy has improved survival. However, cardiovascular complications are a major source of morbidity in cancer survivors. Cardiotoxicity is currently defined by structural myocardial changes and cardiac injury biomarkers. In many instances, such changes are late and irreversible. Therefore, diagnostic modalities that can identify early alterations in potentially reversible biochemical and molecular signaling processes are of interest. This review is focused on emerging translational metabolic imaging modalities. We present in context relevant mitochondrial biology aspects that ground the development and application of these technologies for detection of cancer therapy-related cardiac dysfunction (CTRCD). The application of these modalities may improve the assessment of cardiovascular risk when anticancer treatments with a defined cardiometabolic toxic mechanism are to be used. Also, they may serve as screening tools for cardiotoxicity when novel lines of cancer therapies are applied.

Host Genome Variation is Associated with Neurocognitive Outcome in Survivors of Pediatric Medulloblastoma

Host genome analysis is a promising source of predictive information for long-term morbidity in cancer survivors. However, studies on genetic predictors of long-term outcome, particularly neurocognitive function following chemoradiation in pediatric oncology, are limited. Here, we evaluated variation in host genome of long-term survivors of medulloblastoma and its association with neurocognitive outcome. Whole-genome sequencing was conducted on peripheral blood of long-term survivors of pediatric medulloblastoma who also completed neuropsychological testing. Cognitively impaired and less impaired survivors did not differ in exposure to chemoradiation therapy or age at treatment. Unsupervised consensus clustering yielded two distinct variant clusters that were significantly associated with neurocognitive outcome. Interestingly, 34 of the 36 significant variants were found in noncoding DNA regions with unknown regulatory function. A separate unsupervised cluster analysis of variants within DNA repair genes identified discrete variant groups that were not associated with neurocognitive outcome, suggesting that variations in genes corresponding to a single functional group may be insufficient to predict long-term outcome alone. These findings are supportive of the presence of a genetic diathesis for treatment-related neurocognitive morbidity in medulloblastoma that may be driven by variation in noncoding regulatory elements.

Anti-cancer agents and endothelium

Recent advances in oncology have improved the treatment outcomes and life expectancy of cancer patients; therefore, late effects of oncological treatment are of high clinical importance. Recent studies have shown that cardiovascular events are among the leading causes of premature morbidity in cancer survivors. Cardiotoxicity of some chemotherapeutic agents have been already confirmed; however, this issue seems to be more complex. Endothelium dysfunction is one of the first recognisable signs of atherosclerosis, which occurs long before the development of overt cardiovascular disease. Thus, it could be considered as an initial step, leading to increased risk of cardiovascular events. This process is not easy to recognise; however, there are some laboratory tests and imagining techniques that provide an insight into the progression of endothelial dysfunction. In this review we discuss the influence of oncological treatment on endothelium, according to the hypothesis that it increases cardiovascular morbidity and mortality in cancer survivors. Additionally, we present diagnostic and therapeutic measures that could reduce cardiovascular risk in cancer patients.

Evaluation and management of skeletal disease in cancer care.

Recently, there have been considerable advancements in cancer therapies thereby prolonging the life of cancer survivors. However, these recent advancements present new challenges in the management of bone disease in cancer survivors. Bone acts as a fertile soil for cancer seeding and bone health is often compromised because of increased inflammatory cytokines in cancer, direct cancer metastasis and toxic effects of anti-cancer therapies. This effect is more pronounced in elderly population who already have compromised bone mineral density leading to increased skeletal related events and bone pain. Timely diagnosis and effective interventions are essential for reducing bone-related morbidity in cancer survivors. Also, a complex interdependence exists between cancer related bone disease and tumor growth, creating a vicious circle of extensive bone destruction and cancer progression. Hence, maintenance of bone health and integrity plays a pivotal role in comprehensive cancer care. The bone-targeted treatments have been shown to preserve bone health, and modify the course of the underlying cancer. Management of long-term bone health requires a broad knowledge base that endocrinologists, oncologists and other care team members should be aware of. The manuscript highlights the skeletal effects of cancer, adjuvant therapies used for hormone-responsive cancers, chemotherapy induced bone loss and steps for accurate diagnosis and management of bone disease in cancer survivors by bridging the gaps in the comprehensive cancer care.

Metacognitive Therapy for Emotional Distress in Adult Cancer Survivors: A Case Series

Many adult cancer survivors experience persistent emotional distress after completing cancer treatment. The aim of this study was to test the potential of a brief transdiagnostic psychological intervention—metacognitive therapy (MCT)—in reducing emotional distress in adult cancer survivors. A non-concurrent multiple baseline design with 3- and 6-months follow-up was used to evaluate the effects of MCT in four patients consecutively referred to a psycho-oncology service. Each patient received six 1-h sessions of MCT. Anxiety, depression, worry/rumination, fear of cancer recurrence and metacognitive beliefs were assessed using self-report questionnaires. MCT was associated with clinically significant reductions in anxiety, depression, fear of cancer recurrence, worry/rumination and metacognitive beliefs at the end of treatment, and gains were maintained in all patients to 3-months follow-up and in three out of four patients to 6-months follow-up. MCT is a promising brief transdiagnostic approach to psychological morbidity in adult survivors of cancer. Larger scale controlled trials are now required.

Getting the SCOOP—Survey of Cardiovascular Outcomes From Oncology Patients During Survivorship

BackgroundCardiovascular (CV) disease is the second most common cause of mortality and morbidity in cancer survivors (CS). Limited data exist on the knowledge and awareness of CS about CV effects of cancer therapies and its effect on lifestyle of survivors. It is important to identify gaps in CV care of CS. Materials and MethodsA brief voluntary, anonymous, web-based questionnaire was designed to assess the awareness of CS about the interaction between CV disease, CV symptoms and lifestyle changes from cancer treatment. ResultsA total of 213 volunteers (181 women) with mean age of 56 years responded to the survey. Breast cancer was the most prevalent cancer diagnosis. In all, 15% reported CV disease before therapy with a higher incidence of CV disease in survivors more than 5 years from diagnosis (20% >5 years versus 10% <5 years of survivorship, P = 0.05). The reported use of beta blockers (9%) and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (9%) was rare despite the high incidence of CV disease. Only one-fourth of survivors were offered CV screening during treatment, whereas 36% of survivors had unanswered questions about CV symptoms from therapy. The CV symptoms adversely affected lifestyle in 27% of CS. One-fifth of survivors received exercise counseling even though half would have liked counseling. ConclusionsThe survey demonstrates that CS have self-reported CV symptoms and there may be unmet needs for CV preventive services. Further work is needed to develop collaborative patient counseling and management strategies between oncology and cardiology for improving CV health and symptoms of CS.

Late psychiatric morbidity in survivors of cancer at a young age: a nationwide registry-based study.

Childhood cancer survivors have been shown to be prone to psychosocial adverse outcomes. Data on young adults and their psychiatric late effects are still scarce. In a nationwide, registry-based study, we explored the risk (HR) of new psychiatric diagnoses in 5-year survivors of childhood and young adulthood (YA) cancer (n = 13,860) compared with a sibling cohort (n = 43,392). Hazard ratios (HRs) were calculated using Cox regression models. Patients and siblings were identified from the Finnish Cancer Registry and Central Population Registry, respectively. Outcome diagnoses were retrieved from the national hospital discharge register. The risk of organic memory/brain disorders was significantly increased in both childhood (HR 4.9; 95%CI 2.7-8.9) and YA (HR 2.1; 95%CI 1.4-3.1) cancer survivors compared with siblings. Mood disorders were also more common in childhood (HR 1.3; 95%CI 1.1-1.7) and YA survivors (1.3; 95%CI 1.1-1.5) than in siblings. Radiotherapy did not explain the differences. Female childhood cancer survivors had significantly increased HRs for mood disorders, psychotic disorders, neurotic/anxiety disorders, somatization/eating disorders and personality disorders. In survivors of YA cancers, females had significantly increased HR for neurotic/anxiety disorders, and the difference between female survivors and siblings was significantly (p < 0.05) higher than that between male survivors and male siblings. The effect of treatment era was also analyzed, and the risk of organic memory and brain disorders in childhood cancer survivors did not diminish over time. Despite the trend of decreased use of cranial irradiation in children, the risk of organic memory/brain disorders was elevated, even during the most recent era. Thus, additional research on chemotherapy-only protocols and their impact on mental health, is warranted.

Conquer fear: protocol of a randomised controlled trial of a psychological intervention to reduce fear of cancer recurrence.

BackgroundUp to 70% of cancer survivors report clinically significant levels of fear of cancer recurrence (FCR). Despite the known negative impact of FCR on psychological wellbeing and quality of life, little research has investigated interventions for high FCR. Our team has developed and piloted a novel intervention (Conquer Fear) based on the Self-Regulatory Executive Function Model and Relational Frame Theory and is evaluating Conquer Fear in a randomised controlled trial (RCT). We aim to compare the efficacy and cost-efficacy of the Conquer Fear Intervention and relaxation training in reducing the impact of FCR.Methods/designThis study is a multi-centre RCT with 260 participants randomised either to the Conquer Fear Intervention or relaxation training. Both interventions will be delivered in five sessions over 10 weeks by trained psychologists, psychiatrists and social workers with five or more years experience in oncology. Conquer Fear sessions use attentional training, detached mindfulness, meta-cognitive therapy, values clarification and psycho-education to help patients change the way they regulate and respond to thoughts about cancer recurrence. Relaxation training includes training in progressive and passive muscle relaxation, meditative relaxation, visualisation and “quick relaxation” techniques. Relaxation was chosen to control for therapist time and attention and has good face-validity as an intervention. The primary outcome is fear of cancer recurrence. Secondary outcomes include distress, quality of life, unmet needs, and health care utilisation. Participants complete questionnaires prior to starting the intervention, immediately after completing the intervention, 3 and 6 months later. Eligible participants are early-stage breast or colorectal cancer survivors who have completed hospital-based treatment between 2 months and 5 years prior to study entry and report a score in the clinical range on the Fear of Cancer Recurrence Inventory. The biostatistician is blinded to group allocation and participants are blinded to which intervention is being evaluated. Randomisation is computer generated, stratified by therapist, and uses sequentially numbered sealed envelopes.DiscussionIf successful, the study will provide an evidence-based intervention to reduce psychological morbidity in cancer survivors, and reduce overall health care costs due to more appropriate use of follow-up care and other health services in this very large population.Trial registrationTrial registration: ACTRN12612000404820

Long-term sequelae after cancer therapy--survivorship after treatment for testicular cancer.

This paper is based on a lecture given during the Oncological Forum, Oslo, in November 2002. Long-term morbidity in cancer survivors is exemplified by results of clinical research in testicular cancer survivors (TCSs). The most serious complication is the development of second, non-germ cell malignancies (relative risk [RR]: 1.4-1.6). After infradiaphragmatic radiotherapy, most solid malignancies are diagnosed within or near the target volume. Combined chemo-radiotherapy increases this risk. Chemotherapy-induced leukaemia is usually reported after 4-7 years. After 3 or 4 cycles of cisplatin-based chemotherapy, 15-20% of TCSs suffer from peripheral sensory neuropathy, Raynaud-like phenomena and/or ototoxicity. Hypogonadism is observed in 16%. The risk of cardiac complications is increased by hypercholestorolaemia and abnormal body mass. Pelvic radiotherapy and cisplatin-based chemotherapy are followed by transient oligo/azospermia with recovery after 6-12 months. The risk of surgery-related 'dry ejaculation' is significantly reduced after unilateral and nerve-sparing retroperitoneal lymph node dissection, but infertility remains a long-term problem in 10-15% of survivors. Most TCSs describe their quality of life as comparable with that of the age-matched male general population. Not all long-term complications are avoidable after curative treatment of cancer. Knowledge of post-treatment long-term morbidity is essential for early recognition and treatment of late complications, and enables adequate counselling of new cancer patients.

Surviving cancer.

Research trends on quality of life outcomes for cancer survivors are discussed. Epidemiologic data indicate that female cancer survivors, coming primarily from patient groups with gynecologic, breast, and colorectal cancers, will outnumber male survivors 3 to 1. Male survivors will come from the ranks of patient groups with colorectal and other digestive tumors (such as stomach cancer), prostate, and bladder cancers. With the exception of breast cancer, there have been few well controlled descriptive, longitudinal studies of cancer survivors, with data on men being notably absent. A strategy for identifying differential levels of risk for psychologic morbidity for cancer survivors is proposed. Other important psychologic individual difference variables were identified: control, optimism, and stable coping strategies may be useful in the prediction of mental health outcomes; conscientiousness in the prediction of health behaviors; and sexual self-schema in the prediction of sexual outcomes. Finally, data suggest that psychologic and behavioral outcomes can be improved with psychologic interventions, but it is likely that even greater gains could be achieved if health behavior components were added. New directions for research include study of individual differences, examination of active components of multifaceted interventions, and study of the health consequences of interventions. In the latter regard, a biobehavioral model of stress and cancer is offered to integrate psychologic, behavioral, biologic, and disease factors into testable new research directions.