Venous thromboembolism and cancer: guidelines of the Italian Association of Medical Oncology (AIOM)

Thromboembolic complications represent one of the most important cause of morbidity and mortality in cancer patients. Although several data have been published demonstrating the strong association between cancer and venous thromboembolism (VTE), there is poor perception, among oncologists, of the level of risk of thrombosis and of relevance of managing VTE in these patients. The Associazione Italiana di Oncologia Medica (AIOM) has provided some recommendations to direct clinical practice according to evidence-based data concerning cancer and VTE. In fact, we conducted an extensive literature review (1996-2005) to produce evidence-based recommendations to improve perceptions of the magnitude of this risk among Italian medical and surgical oncologists and alert on the new approaches to prophylaxis and treatment of VTE in cancer patients. Levels of evidence are given according to a five-point rating system, and similarly for each key recommendation a five-point rating system suggests if the evidence is strong and indicate that the benefits do, or do not, outweigh risks and burden.     

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??Abstract??Venous thromboembolism (VTE) represents one of the most important causes of morbidity and mortality in cancer patients.Hypercoagulability??stasis and vessel wall injury??which are the mechanisms of VTE??are associated with cancer or chemotherapy.There are several factors that might increase the risk of VTE??including those related to patients themselves??cancer or treatments.But most of oncologists have underestimated the prevalence of VTE and its negative impact on their patients.Measurements should be taken to enhance the perceptions about magnitude of VTE risk in patients with malignancy and to improve prophylaxis and treatment of VTE in cancer patients.     

Chemotherapy-Induced Arrhythmia – Underrecognized and Undertreated

Cancer is one of the leading causes of death worldwide. Chemotherapy-induced arrhythmia is a potential complication of treatment that confers increased morbidity and mortality. The relationship between chemotherapeutic agents and arrhythmias is poorly established. Atrial fibrillation, ventricular ectopic beats, and prolonged QTc are the most common arrhythmias suffered by cancer patients undergoing chemotherapy. The treatment of atrial fibrillation in cancer is complicated by complex drug–drug interactions and a lack of evidence guiding practice. Furthermore, the normal risk assessment scores utilized in the decision-making for anticoagulation in the normal population are not validated in the cancer population. Multiple agents are implicated in prolonging the QTc, and this can often have adverse consequences for both the patient and the treatment of their cancer. This can manifest as torsades de pointes and sudden cardiac death. It is advised that, during treatment, oncologists should have close liaison with cardio-oncologists to ensure optimum patient management.     

Adjuvant treatment recommendations in older women with breast cancer: a survey of oncologists

OBJECTIVE: Previous studies demonstrate differing treatment patterns between older and younger patients with breast cancer. To explore the reasons for these disparities we conducted a survey of 28 oncologists specializing in breast cancer. DESIGN AND METHODS: Twenty-eight medical oncologists from Memorial Sloan-Kettering Cancer Center and the University of California Los Angeles who specialize in the treatment of breast cancer were asked to provide adjuvant treatment recommendations in hypothetical scenarios featuring older patients with high-risk breast cancer. For each of these hypothetical patients, the patient's age was varied over four possible values (70, 75, 80, or 85 years of age) and health and functional status varied across three possible states (perfect health, average health, or major health problems). Survey data were compiled and analyzed to determine the impact of theoretical patient age, baseline health, and functional status on their treatment recommendations. RESULTS: The proportion of oncologists who recommended adjuvant chemotherapy decreased as the patient's age increased or as the patient's functional status and health status decreased. For 96% of physicians (95% CI, 82-100%), patient age influenced chemotherapy recommendations, controlling for health/functional status; the same proportion of respondents were influenced by health/functional status, controlling for patient age. There was increased variability in treatment recommendations as the patient's age increased or functional status and health status decreased. CONCLUSION: Among these medical oncologists who primarily treat breast cancer adjuvant treatment recommendations vary based on patient age, health, and functional status. Future studies are needed to correlate age, health, and functional status with the risks and benefits of adjuvant therapy so that consensus guidelines can be formed. A more comprehensive baseline assessment of the older patient, such as can be derived from a comprehensive geriatric assessment may be useful in this regard.     

Malignant disease in the haemophilic population: moving towards a management consensus?

The Malignancy in Haemophilia Workshop Group convened a consensus working group of haematologists and oncologists to review topics related to malignancy in haemophilia. The treatment of malignant disease in this population is increasingly relevant as both outcome and lifespan continue to improve. Although adequate guidance exists for control of spontaneous bleeding episodes and of haemostasis in general surgery, information for management of haemostasis in patients with various malignancies is sparse. To date, no clinical guidelines exist for management of complex bleeding problems, diagnosis, therapy and follow-up of malignancies in haemophilia. Furthermore, it remains unclear whether or not morbidity and mortality outcomes associated with malignancies are affected by haemophilia or by its treatment. Through presentation of five malignancies - prostate cancer, colorectal cancer, acute leukaemia, bladder cancer and hepatocellular carcinoma - important issues are highlighted, such as risk from bleeding as a symptom of malignancy; risks from invasive screenings and how these should be handled in haemophilic individuals; the implications of chemotherapy and treatment schedules, bone marrow suppression, radiotherapy, or surgery; and the likelihood of an interaction between treatment for haemophilia and malignancy outcomes. Ultimately, the aim is to establish consensus guidelines to direct and harmonize future treatment policy for malignant disease in the haemophilic population.     

Treatment of cardiovascular diseases in cancer patients

Cardiovascular diseases and cancer are the leading causes of death in the Western world. Cancer treatment has been associated with cardiovascular complications, among others cardiotoxicity of mediastinal radiation and certain chemotherapeutics. Identification of patients at high risk, prevention, early diagnosis, and treatment of cardiovascular diseases are emerging fields in cancer patients. Close interdisciplinary work between oncologists and cardiologists is pertinent for the treatment of cardiovascular diseases and complications in cancer patients. Diagnostics and treatment applied to the individual case should be based on the available evidence in terms of patient-centered management. Further clinical research focused on the pathogenesis and treatment of cardiovascular diseases in cancer patients is warranted to pave the way to guidelines for this nonhomogeneous patient group.     

Vasospastic angina likely related to cisplatin-containing chemotherapy and thoracic irradiation for lung cancer.

Vasospastic angina is rarely observed during cancer treatment. The present report describes two males with lung cancer, aged 73 and 61, who developed vasospastic angina during combination treatment of cisplatin-containing chemotherapy and thoracic irradiation. As both patients have smoked and their ages are typical for patients with coronary artery disease, such events may be incidental. However, oncologists should be aware of the possible development of myocardial ischemia during or following administration of antineoplastic agents, especially in elderly patients with pre-existing coronary risk factors or a history of thoracic radiotherapy.     

Addressing hepatic metastases in ovarian cancer: Recent advances in treatment algorithms and the need for a multidisciplinary approach

The lifetime risk for ovarian cancer incidence is 1.39% and the lifetime risk of death is 1.04%. Most ovarian cancer patients are diagnosed at advanced stages(Ⅲ, Ⅳ) because there were no specific symptoms or existing screening tests. Liver metastases have been found in up to 50% of patients dying of advanced ovarian cancer. Recent studies indicate the need for a multidisciplinary approach from initial diagnosis to oncologic surgery and chemotherapy treatment, mandating the involvement of gynecologic oncologists, surgical oncologist, medical oncologists, hepatobiliary surgeons, and interventional radiologists.     

Cancer and age: general considerations

Cancer in the older person is increasingly common. The biological interactions of cancer with age are only partly understood and may provide some clues to future forms of cancer prevention and treatment. Management-related decisions in a population with limited life expectancy and limited functional reserve should be based on the natural history of the cancer, the patient’s life expectancy, and the patient’s tolerance of treatment. In addition, financial and caregiver considerations are important in assessing the treatment’s benefits and risks. Cooperation between geriatricians and oncologists seems to be essential to generate predictive models, as well as outcome information to improve the decision making in older cancer patients. It may also be essential in caring for a host of older cancer survivors. In France, this cooperation is already a reality that finds its expression in a network of units of oncogeriatrics distributed throughout the country.     

Clinical vignettes: integrated care of cancer patients by oncologists and cardiologists

Because of the paucity of large, randomized trials concerning the cardiac care of patients with cancer, treatment and prevention of chemotherapy-induced cardiotoxicity must rely on insights gained from small trials and case reports as well as the application of guidelines developed for the general population. In these clinical vignettes, we present patients referred by their oncologists to a cardiologist for specialized evaluation and management of cardiotoxicity with the goal of emphasizing the importance of identifying risk factors for cardiotoxicity, initiating evidence-based therapy, and establishing a close collaboration between oncologists and cardiologists.     

Thrombosis and lung cancer

This relation is sometimes described as a double association: venous thromboembolism (VTE) can reveal cancer (so-called Trousseau syndrome), but cancer and its treatment are also risk factors for VTE. Lung cancer, frequent and serious, is one of the greatest purveyors of VTE, a disease that pneumologists and oncologists must often confront in diagnosis, prevention, and treatment. This article investigates the epidemiological, prevention, and treatment aspects of VTE in cancer patients, particularly those with lung cancer, but also discusses diagnostic specificities and, briefly, the possible antitumor effect of heparins.     

Gastric cancer confined to the muscularis propria: a possible candidate for laparoscopic surgery or adjuvant therapy

OBJECTIVE: Gastric cancer confined to the muscularis propria (mp) has a favorable prognosis, but still belongs to the advanced category. Many oncologists have difficulties in selecting treatment modalities owing to the confused situation of mp cancer. To clarify the therapeutic strategy, the clinicopathological characteristics were investigated, and the risk factors, of this intermediate-stage gastric cancer, evaluated. MATERIAL AND METHODS: A total of 155 patients who underwent curative resection for primary gastric cancer between 1993 and 2001 were diagnosed with mp cancer. The patients were divided into recurrent and non-recurrent groups and analyzed clinicopathologically. RESULTS: The rate of recurrence was 20%. A multivariate analysis disclosed only lymphatic metastasis as an independent risk factor for recurrence of mp cancer. Hematogenous metastasis accounted for 37% of the recurrent patterns, and the liver (83.3%) was the most common organ. The 5-year survival rate of all mp cancer patients was 80.9%, but that of patients with recurrent disease was 19.2%. The median survival time of the recurred patients was 24 months, and 74% of those patients died within 3 years. CONCLUSIONS: Lymph node metastasis is the only significant risk factor of mp cancer. Patients with lymphatic metastasis should undergo postoperative adjuvant therapy. On the other hand, patients with mp cancer without lymph node involvement have an excellent prognosis and could be candidates for laparoscopic gastric surgery.     

Intensified chemotherapy of solid tumours

Treatment of solid malignant diseases is despite significant scientific advances during the last decade still a problem. The results of treatment do not satisfy oncologists. New substances are sought which influence the proliferation of malignant cells and some of them are promising. At present however rather new therapeutic approaches are sought which use already known cytostatic substances. With the help of hithero known laws of chronobiology therapeutic regimes are elaborated which are less toxic than classical standard administration. The advances of high-dose chemotherapy in haematooncology led oncologists to create intensified cytostatic therapeutic regimes also for solid malignant diseases. The most extensive experience was obtained with such approaches in breast cancers, germinal tumours of the testes and partly also of the ovaries. The great importance of breast cancer in oncological problems caused that experience with high-dose cytostatic treatment are most extensive. Results of this treatment were assembled in particular from the North American register and compared with conventional treatment. Metastatic diseases and inflammatory breast cancer did not have significantly remarkable results as compared with classical treatment and therefore they were abondoned. Promising seemed the results of adjuvant treatment of patients with a high risk of relapse. Further studies presented at ASCO (American Society of Clinical Oncology) 1998 however did not confirm these hopes and shifted high-dose therapy only to strictly followed up clinical studies. On the other hand mathematical models based on cytokinetic and pharmacodynamic studies prove a possible complete eradication of malignant cells in case of adjuvant administration in high risk patients. A pattern was elaborated, doxorubicin-paclitaxel-cyclophosphamide in a so-called dose density regime (with shortened intervals between cycles of chemotherapy and with a higher or equal dosage of cytostatics than is common). This regime is still the subject of studies, nevertheless preliminary results from the aspect of total survival and toxicity are statistically significant. The application of this regime is so far possible only in specialized centres such as Masaryk's Oncology Institute in Brno.     

Current approach to relapsed acute lymphoblastic leukemia in children

Recurrent acute lymphoblastic leukaemia(ALL) is a common disease for pediatric oncologists and accounts for more deaths from cancer in children than any other malignancy. Although most patients achieve a second remission, about 50% of relapsed ALL patients do not respond to salvage therapy or suffer a second relapse and most children with relapse die. Treatment must be tailored after relapse of ALL, since outcome will be influenced by well-established prognostic features, including the timing and site of disease recurrence, the disease immunophenotype, and early response to retrieval therapy in terms of minimal residual disease(MRD). After reinduction chemotherapy, high risk(HR) patients are clear candidates for allogeneic stem cell transplantation(SCT) while standard risk patients do better with conventional chemotherapy and local therapy. Early MRD response assessment is currently applied to identify those patients within the more heterogeneous intermediate risk group who should undergo SCT as consolidation therapy. Recent evidence suggests distinct biological mechanisms for early vs late relapse and the recognition of the involvement of certain treatment resistance related genes as well cell cycle regulation and B-cell development genes at relapse, all providing the opportunity to search for novel target therapies.     

Prior cancer diagnosis and mortality profile in US adults

BackgroundMortality profiles with multivariate adjustment in patients with a prior cancer diagnosis are scarce. This study aimed to investigate multivariate-adjusted mortality profile in US adults with a prior cancer diagnosis.MethodsThis cohort study included 58,109 US adults (5,016 with a prior cancer diagnosis) who attended the National Health and Nutrition Examination Survey. Mortality outcomes were ascertained by linkage to the National Death Index records. Cox proportional hazards models were used to estimate hazard ratios (HRs) and confidence intervals (CIs) of prior cancer diagnosis for mortality.ResultsThis cohort was followed up for 646,033 person-years with a mean follow-up of 11.1 years. Compared with those without cancer, participants with a prior cancer diagnosis had increased crude cumulative mortality rates in each leading cause. Prior cancer diagnosis was associated with a higher multivariate-adjusted risk of mortality from all causes (HR, 1.29; 95% CI, 1.22-1.35), cancer (HR, 2.32; 95% CI, 2.10-2.56), and accidents (HR, 1.90; 95% CI, 1.34-2.68). Prior cancer diagnosis-associated increase in accident mortality appeared only in males and was significant only in non-Hispanic black participants. Prior cancer diagnosis-associated increase in cancer mortality appeared high in non-Hispanic black participants.ConclusionsThis study found that patients with a prior cancer diagnosis had higher multivariate-adjusted accident mortality risks, suggesting that oncologists may need to evaluate accident risks in cancer patients and provide preventive interventions in particular for male and non-Hispanic black patients. Increased cancer mortality risk associated with prior cancer diagnosis in non-Hispanic black participants may also need clinical attention.     

Artificial Neural Network: Predicted <Emphasis Type="Italic">vs</Emphasis>. Observed Survival in Patients with Colonic Cancer

Purpose An Internet-web-based artificial neural network has been developed for practicing clinical oncologists and medical researchers as part of an ongoing program designed for the implementation of advanced neural networks for prognostic estimates and eventually for management/treatment decisions in individual patients with colonic cancer. Methods An interdisciplinary team of academic oncologists and physicists has configured and implemented a Partial Logistic Artificial Neural Network and trained it to predict cancer-related survival in patients with confirmed colorectal cancer by using a database (1,558 patients) made available for the study by the Information & Statistics Division of National Health Service Scotland. The reliability of the trained network was evaluated against Kaplan-Meier observed survival plots of a random sample of 300 patients not used in the training but forming part of the same data set. Results The predicted survival curves obtained as the output from the artificial neural network showed close agreement with observed actual survival rates of a cohort of 300 patients with four grades of risk of dying from the cancer within five years of diagnosis. Conclusions The web-based Partial Logistic Artificial Neural Network system accurately predicts survival after staging and treatment of colonic cancer. It can be made web-accessible where it is powerful enough to serve hundreds of users simultaneously. Supported by a grant from the Medical Research Council (UK) to Professor Robin Marshall and Professor Sir Alfred Cuschieri.     

Late endocrine,metabolic and skeletal sequelae following treatment of childhood cancer

With an ever increasing adult population of childhood cancer survivors there is a need to focus on the late effects of cancer therapy. It is essential that, after discharge from the paediatric oncologists, the patients are not lost from the health system but are under continued surveillance with access to the appropriate physicians. Endocrine and metabolic consequences may affect a patient's life both soon after cancer treatment and also for many years in the future. In this review we consider the following potential problems: growth hormone deficiency and replacement in adulthood, cardiovascular risk factors, osteopaenia, thyroid and parathyroid dysfunction.     

Supportive and palliative care of pancreatic cancer

Pancreatic cancer is one of the most lethal malignancies. An estimated 32,300 patients will die of pancreatic cancer in year 2006. It is the tenth most common malignancy in the United States. Despite recent advances in pathology, molecular basis and treatment, the overall survival rate remains 4% for all stages and races. Palliative care represents an important aspect of care in patient with pancreatic malignancy. Identifying and treating disease related symptomology are priorities. As a physician taking care of these patients it is essential to know these symptoms and treatment modalities. This review discusses symptom management and supportive care strategies. Common problems include pain, intestinal obstruction, biliary obstruction, pancreatic insufficiency, anorexia-cachexia and depression. Success is needed in managing these symptoms to palliate patients with advanced pancreatic cancer. Pancreatic cancer is a model illness to learn the palliative and supportive management in cancer patient. It is important for oncologists to recognize the importance of control measures and supportive measures that can minimize the symptoms of advanced disease and side effects of cancer treatment.     

Anticancer drug treatment for advanced lung cancer with interstitial lung disease

Interstitial lung disease (ILD) is a risk factor for lung cancer development and is frequently observed in patients with lung cancer. Individuals with ILD have been excluded from most prospective clinical trials of lung cancer therapies because of the risk of ILD acute exacerbation. Thus, the optimal anticancer drug treatment for such patients has yet to be established. Tyrosine kinase inhibitors are avoided for the treatment of advanced non–small cell lung cancer (NSCLC) with ILD because of the concern of acute exacerbation, and information on the effects of immune-checkpoint inhibitors is limited in these patients. Only three prospective single-arm studies of cytotoxic chemotherapies for advanced lung cancer with ILD have been reported. Based on the results of these studies and those of retrospective analyses, carboplatin and either paclitaxel or nab-paclitaxel are often selected in daily clinical practice for patients with NSCLC and ILD, whereas platinum plus etoposide is selected for those with small cell lung cancer and ILD. Although the antitumor activity of first-line platinum-based chemotherapy appears similar in advanced lung cancer patients with and without ILD, its impact on overall survival of the former patients is limited. The risks and benefits of chemotherapy must therefore be carefully explained before treatment initiation, and careful follow-up is necessary for such patients, especially those with the usual interstitial pneumonia pattern, a risk factor for chemotherapy-related exacerbation. Prospective clinical studies with large patient populations are still required to establish the appropriate treatments for advanced lung cancer with ILD.     

Geriatric assessment for oncologists: rationale and future directions

Sixty percent of all cancer occurrences and seventy percent of cancer mortalities occur in people over the age of 65. As the population ages, there is an emerging need to develop a means for oncologists to characterize the "functional age" of older patients with cancer in order to tailor treatment decisions and stratify outcomes based on factors other than chronological age and to develop interventions to optimize cancer treatment. In this paper, we discuss the formulation of a geriatric assessment for older patients with cancer. The measures included in this assessment were chosen based on their validity, reliability, brevity, adaptability for self-administration, and ability to prognosticate risk for morbidity or mortality in an older patient. The proposed geriatric assessment covers the essential domains of assessment predictive of survival in the geriatric population, is primarily self-administered, and limited personnel time is required. Our eventual goal is to determine if this geriatric assessment measure can identify factors independent of age that predict cancer treatment morbidity and mortality and result in rationale interventions to optimize oncologic care.