Literature review and practical aspects on the management of oxaliplatin-associated toxicity

Colorectal cancer is currently a public health priority because it is the second leading cause of cancer deaths in Western countries. Combination regimes of oxaliplatin and infusional fluorouracil/leucovorin or capecitabine have emerged as important options in the palliative and adjuvant treatment of colorectal cancer. Although better tolerated than cisplatin, oxaliplatin displays a characteristic profile of adverse events whose recognition and management are essential for physicians who treat patients with colorectal cancer and other malignancies that benefit from the use of oxaliplatin. Peripheral neuropathy is probably the most frequent and clinically relevant adverse event associated with the use of oxaliplatin, and several measures have been proposed to mitigate this toxicity. Temporary interruption of oxaliplatin before limiting neurotoxicity develops during therapy is a potential approach to avoid the problem of oxaliplatin-associated neuropathy in patients with metastatic colorectal cancer. Calcium and magnesium infusions have no effect on chemotherapy efficacy and also constitute a useful approach in clinical practice. Finally, the incidence and severity of chronic peripheral neuropathy in patients treated with oxaliplatin may be reduced by the use of neuroprotective agents, for example, venlafaxine. Other adverse events, such as gastrointestinal and liver toxicity, thrombocytopenia, and hypersensitivity reactions, are also reviewed in this article, and suggestions are made for their management.     

Minimizing risk of hypomethylating agent failure in patients with higher-risk MDS and practical management recommendations

In Europe, azacitidine is the only hypomethylating agent approved for the treatment of patients with int-2-/high-risk myelodysplastic syndromes, offering significantly improved survival compared with conventional care. However, not all patients treated with azacitidine respond to treatment, and the vast majority of responders subsequently relapse. Currently, no standard care regimens have been established for patients after failure of azacitidine. Here, we discuss treatment options after loss of response or progression on azacitidine. In addition, we briefly consider optimization of first-line treatment along with potential biomarkers for identifying and monitoring response during treatment with azacitidine.     

Comprehensive Review of AL amyloidosis: some practical recommendations

Amyloid light chain (AL) amyloidosis is among the more common and more severe of the amyloidoses usually involving the slow proliferation of a bone-marrow-residing plasma cell (PC) clone and the secretion of unstable immunoglobulin-free light chains (FLC) that infiltrate peripheral tissues and result in detrimental end-organ damage. Disease presentation is rather vague, and the hallmark of treatment is early diagnosis before irreversible end-organ damage. Once diagnosed, treatment decision is transplant-driven whereby ~20% of patients are eligible for autologous stem cell transplantation (ASCT) with or without bortezomib-based induction. In the setting of ASCT-ineligibility, bortezomib plays a central role in upfront treatment with the recent addition of daratumumab to the current emerging standard of care. In general, management of AL amyloidosis is aimed at achieving deep, durable responses with very close monitoring for early detection of relapse/refractory disease. This article provides a comprehensive review of the management of patients with AL amyloidosis including goals of therapy, current treatment guidelines in the setting of both ASCT-eligibility and ineligibility, treatment response monitoring recommendations, toxicity management, and treatment of relapse/refractory disease.Subject terms: Haematological diseases, Immunotherapy, Combination drug therapy     

Clinical breast examination: practical recommendations for optimizing performance and reporting

Clinical breast examination (CBE) seeks to detect breast abnormalities or evaluate patient reports of symptoms to find palpable breast cancers at an earlier stage of progression. Treatment options for earlier-stage cancers are generally more numerous, include less toxic alternatives, and are usually more effective than treatments for later-stage cancers. For average-risk women aged 40 and younger, earlier detection of palpable tumors identified by CBE can lead to earlier therapy. After age 40, when mammography is recommended, CBE is regarded as an adjunct to mammography. Recent debate, however, has questioned the contributions of CBE to the detection of breast cancer in asymptomatic women and particularly to improved survival and reduced mortality rates. Clinicians remain widely divided about the level of evidence supporting CBE and their confidence in the examination. Yet, CBE is practiced extensively in the United States and continues to be recommended by many leading health organizations. It is in this context that this report provides a brief review of evidence for CBE's role in the earlier detection of breast cancer, highlights current practice issues, and presents recommendations that, when implemented, could contribute to greater standardization of the practice and reporting of CBE. These recommendations may also lead to improved evidence of the nature and extent of CBE's contribution to the earlier detection of breast cancer.     

Human tissue research: EORTC recommendations on its practical consequences

Improvement in cancer care is possible by applying new treatment modalities, which are emerging from knowledge and discoveries coming from laboratory research. This is possible through international collaboration and the collection of tumour tissues. Creation of a European Organisation for Research and Treatment of Cancer (EORTC) Tumor Bank is a natural step in this direction, by offering tumour sample collection from patients entered in EORTC trials. The aim of such a bank is not only to improve the diagnostic review process, but also to facilitate translational research by allowing clinicians and basic scientists to enter into close collaborations. The EORTC Tissue Research Policy is developed to assure, under the EORTC legal framework, an ethical and scientific review of research projects, guarantee adequate information is given to patients, establish procedures on the use of materials, including legal aspects, and publication policies. Being part of the EU TubaFrost project, the EORTC will provide a common international platform for the use of tissues for research purposes, finding a balance between different laws and assuring scientific progress.     

Tyrosine kinase inhibitors and drug interactions: a review with practical recommendations

The adverse effects associated to traditional chemotherapy are well known and broadly studied. In the recent years several tyrosine kinase inhibitors have been approved for cancer treatment and numerous are under investigation. These drugs target specific mutated/overexpressed tyrosin kinase receptors and frecuently their pharmacokinetic/pharmacodinamic behavior is not fully elucidated. These new drugs may interact with non-antineoplastic drugs leading to undesirable adverse effects. In this article, we will discuss different types of drug interactions and briefly review the pharmacokinetics and mechanisms of action of tyrosine kinase inhibitors in clinical use, with a particular emphasis on the risk of the occurrence of such interactions based on currently available scientific evidence.     

Chemotherapy-induced cardiac toxicity and management

Cardiac toxicity due to anti-neoplastic agents has been recognized since doxorubicin, one of the most effective anthracyclines, was introduced in the early 1970s. Although the frequency of cardiac toxicity is relatively low compared with hematological and gastrointestinal toxicity, management of cardiac toxicity is crucial because of the possibility of irreversible cardiac damage. Recently, high dose-intense chemotherapy with G-CSF and stem cell transplantation, and mediastinal irradiation, produce even more toxic effects on the heart. This review describes some of the cardiac toxicity of anthracyclines and trastuzumab, and discusses attempts at management. The mainstay of management of cardiac toxicity is serial, adequate monitoring of cardiac functions.     

Management of patients with lymphoma and COVID-19: Narrative review and evidence-based practical recommendations

Patients with hematologic malignancies can be immunocompromized because of their disease, anti-cancer therapy, and concomitant immunosuppressive treatment. Furthermore, these patients are usually older than 60 years and have comorbidities. For all these reasons they are highly vulnerable to infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and have an increased risk of developing severe/critical Coronavirus disease 2019 (COVID-19) compared to the general population. Although COVID-19 vaccination has proven effective in reducing the incidence of severe/critical disease, vaccinated patients with lymphoma may not be protected as they often fail to develop a sufficient antiviral immune response. There is therefore an urgent need to address the management of patients with lymphoma and COVID-19 in the setting of the ongoing pandemic. Passive immunization with monoclonal antibodies against SARS-CoV-2 is a currently available complementary drug strategy to active vaccination for lymphoma patients, while monoclonal antibodies and antiviral drugs (remdesivir, ritonavir-boosted nirmatrelvir, and molnupiravir) have proven effective in preventing the progression to severe/critical COVID-19. In this narrative review we present the most recent data documenting the characteristics and outcomes of patients with concomitant lymphoma and COVID-19. Our ultimate goal is to provide practice-oriented guidance in the management of these vulnerable patients from diagnosis to treatment and follow-up of lymphoma. To this purpose, we will first provide an overview of the main data concerning prognostic factors and fatality rate of lymphoma patients who develop COVID-19; the outcomes of COVID-19 vaccination will also be addressed. We will then discuss current COVID-19 prophylaxis and treatment options for lymphoma patients. Finally, based on the literature and our multidisciplinary experience, we will summarize a set of indications on how to manage patients with lymphoma according to COVID-19 exposure, level of disease severity and former history of infection, as typically encountered in clinical practice.     

免疫检查点抑制剂所致广谱毒性及其危重症的多学科联合应对

免疫检查点抑制剂(ICI)作为新型免疫治疗手段,是继化疗、靶向治疗、抗血管生成治疗后又一新兴的抗肿瘤治疗方式,已经为恶性肿瘤患者带来了显著的生存获益。但其产生的免疫相关不良反应(irAE)的总体发生率达79%～82%,irAE极大地影响了临床治疗决策,且在一定程度上限制了其临床应用和患者持续获益。几乎患者的所有器官系统都可能受到irAE的影响,其广谱性、特殊性、复杂性和多样性极大地增大了临床诊治的难度。充分认识和早期识别重度irAE对于避免发生危重症毒性相关的死亡尤为重要,危重症irAE特别需要多学科诊疗协作组(MDT)的联合应对。对诊断不明的、病情危重的、治疗效果欠佳的irAE,或者毒性缓解后是否重启免疫治疗的患者均需要规范化、标准化的MDT诊疗,故建立以患者为中心的irAE-MDT模式,以循证医学和相关指南/共识为依据,救治危重疑难irAE,将使肿瘤患者从免疫治疗中获益最大化。     

Superior vena cava obstruction syndrome: recommendations for management

The main cause of superior vena cava syndrome (SVCS) is malignant disease. However, multiple other diseases must be considered in the differential diagnosis and a new entity, SVCS due to central venous catheters, represents an etiology of increasing importance. SVCS due to malignancy should not be considered as a radiotherapeutic emergency. Careful management including invasive procedures such as mediastinoscopy to make a definite diagnosis should be performed when necessary by skilled practitioners, as specific therapy depends on a histologic diagnosis. Irradiation remains the standard treatment for many solid tumours, particularly non-small cell lung cancer. For chemosensitive tumours such as small cell bronchogenic carcinoma or lymphoma, chemotherapy can be recommended as initial treatment, and it is associated with high regression rates of the SVCS. In the case of a recent thrombosis of the superior vena cava, fibrinolytics may be applied as suggested by the experience obtained with central venous catheters.     

A practical guide for the management of gliomas

The management of gliomas in daily clinical practice is challenging. It requires a multidisciplinary and coordinated approach involving neurosurgery, radiotherapy and, finally, chemotherapy. Important progress has been made during the last years with the introduction of a combined treatment associating standard radiotherapy with concomitant chemotherapy using temozolomide, a novel alkylating agent. For the first time in many years a new treatment strategy translated into a significant prolongation of survival. In parallel, molecular markers (e.g. loss of heterozygosity on chromosomes 1p and 19q or methylation of the methyl-guanine methyl transferase [MGMT] gene promoter) allowed for identification of distinct subtypes of glioma or prediction of treatment response. In this "Practical Guide", we describe the daily practice and aim at answering some common questions in the management of patients suffering from glioblastoma, astrocytoma, oligodendroglioma and low grade glioma. The therapeutic options presented here are based on evidences from the literature. In the absence of documented evidence, the empirical choices from our local practice are explained and justified.     

Multidisciplinary Canadian consensus recommendations for the management and treatment of hepatocellular carcinoma

Globally, hepatocellular carcinoma (hcc) is the third most common cause of death from cancer, after lung and stomach cancer. The incidence of hcc in Canada is increasing and is expected to continue to increase over the next decade. Given the high mortality rate associated with hcc, steps are required to mitigate the impact of the disease. To address this challenging situation, a panel of 17 hcc experts, representing gastroenterologists, hepatologists, hepatobiliary surgeons, medical oncologists, pathologists, and radiologists from across Canada, convened to provide a framework that, using an evidence-based approach, will assist clinicians in optimizing the management and treatment of hcc. The recommendations, summarized here, were developed based on a rigorous methodology in a pre-specified process that was overseen by the steering committee. Specific topics were identified by the steering committee and delegated to a group of content experts within the expert panel, who then systematically reviewed the literature on that topic and drafted the related content and recommendations. The set of recommendations for each topic were reviewed and assigned a level of evidence and grade according to the levels of evidence set out by the Centre for Evidence-based Medicine, Oxford, United Kingdom. Agreement on the level of evidence for each recommendation was achieved by consensus. Consensus was defined as agreement by a two-thirds majority of the 17 members of the expert panel. Recommendations were subject to iterative review and modification by the expert panel until consensus could be achieved.     

Chemotherapy-induced pulmonary toxicity in lung cancer management

Chemotherapy is the cornerstone of therapy in many stages of lung cancer. Many diagnostic options have to be taken into account when a patient suffering from lung cancer presents with nonspecific, respiratory, clinical manifestations. A multidisciplinary diagnostic approach is then warranted. The top priority is to rule out those life-threatening causes, such as lung infection, that could be properly treated if a right diagnosis is early. To reach a definite diagnosis frequently requires that one or more diagnostic, pneumologic techniques are performed. Regarding to drug-induced pulmonary disease, prevention is mandatory. In this review we have tried to highlight the risk and characteristics of cytostatic-induced pulmonary toxicity caused by those agents that have been commonly employed to treat lung cancer for the last decades. When treating lung cancer patients, a high clinical suspicion of chemotherapy-induced lung toxicity should be kept in mind since an early withdrawal of the offending drug is the most efficacious therapy.     

Dyshaemopoiesis in adults: a practical classification for diagnosis and management

Dyshaemopoiesis is a heterogeneous disease that may be classified into non-clonal and clonal dyshaemopoiesis. Non-clonal dyshaemopoiesis comprises reversible disorders with DNA synthesis impairment in dividing cells of the bone marrow by avitaminosis through various mechanisms or direct DNA damage from multiple causes. Complete haematologic recovery is obtained after vitamin supplementation or suppression of a myelotoxic agent. On the contrary, clonal dyshaemopoiesis is a group of chronic and usually irreversible diseases that may culminate in acute leukaemia (AL). These so called myelodysplastic syndromes (MDS) and their variants may be classified as primary, secondary and other diseases with doubtful clonality. A detailed classification of dyshaemopoiesis in adults may offer partial help in the diagnosis and management of dyshaemopoiesis. Pathobiological studies in progress allow better understanding of MDS and consequently the establishment of new modalities of treatment.     

Sarcoidosis in India: practical issues and difficulties in diagnosis and management

Although sarcoidosis has emerged as an important lung disease in this country, clinicians continue to face difficulties in diagnosis and management of the illness. The relative rarity of sarcoidosis and the remarkable similarity of clinical, radiological and histopathological features with tuberculosis pose problems in the differential diagnosis. Although the pattern and sites of involvement do help, the prevalence of tuberculosis, including those of extrapulmonary sites, is so high that a confident exclusion of the illness is not easy. One important point of difference is the presence of tuberculin-anergy in sarcoidosis vis à vis tuberculosis. Bronchoscopic transbronchial lung biopsy is positive in over 80 percent of patients with sarcoidosis. Exclusion of tuberculosis to diagnose sarcoidosis is important in particular because corticosteroids form the mainstay of treatment for sarcoidosis. Asymptomatic patients with stage I pulmonary and other milder forms of cutaneous sarcoidosis do not need systemic steroid therapy. We have found favorable results with steroid sparing drugs such as methotrexate and azathioprine. Patients with refractory disease, relapse of illness and those with steroid induced complications or concomitant illnesses likely to be worsened by corticosteroids, are mostly treated with weekly, low-dose methotrexate.     

Radiation therapy-associated toxicity: Etiology,management, and prevention

Radiation therapy (RT) is a curative treatment for many malignancies and provides effective palliation in patients with tumor-related symptoms. However, the biophysical effects of RT are not specific to tumor cells and may produce toxicity due to exposure of surrounding organs and tissues. In this article, the authors review the clinical context, pathophysiology, risk factors, presentation, and management of RT side effects in each human organ system. Ionizing radiation works by producing DNA damage leading to tumor death, but effects on normal tissue may result in acute and/or late toxicity. The manifestation of toxicity depends on both cellular characteristics and affected organs' anatomy and physiology. There is usually a direct relationship between the radiation dose and volume to normal tissues and the risk of toxicity, which has led to guidelines and recommended dose limits for most tissues. Side effects are multifactorial, with contributions from baseline patient characteristics and other oncologic treatments. Technological advances in recent decades have decreased RT toxicity by dramatically improving the ability to deliver RT that maximizes tumor dose and minimizes organ dose. Thus the study of RT-associated toxicity is a complex, core component of radiation oncology training that continues to evolve alongside advances in cancer management. Because RT is used in up to one-half of all patients with cancer, an understanding of its acute and late effects in different organ systems is clinically pertinent to both oncologists and nononcologists.