Management of immune-related adverse events resulting from immune checkpoint blockade

Introduction: Immune checkpoint inhibitors (ICI) are now a standard of care in the treatment of many cancers leading to durable responses in patients with metastatic disease. These agents are generally well tolerated but may lead to the occurrence of immune-related adverse events (irAEs). As any organ may be affected, clinicians should be aware of the broad range of clinical manifestations and symptoms and keep in mind that toxicities may occur late, at any point along a patient’s treatment course. Although the most common irAEs are rarely severe, some of them may be associated with great morbidity and even become life-threatening. The rate of occurrence, type and severity of irAEs may vary with the type of ICI; thus, grade 3 and 4 irAEs are reported in more than 55% of patients treated with the combination of ipilimumab 3 mg/kg and nivolumab 1 mg/kg.

Area covered: This review presents the management of irAEs resulting from checkpoint blockade, with a focus on rare irAEs.

Expert commentary: With the development of immuno-oncology and the expanding role of ICI, physicians have learnt to diagnose and treat most of the irAEs that can occur. This review provides an overview of current guidelines, previously published studies and our multidisciplinary team based practices.     

Optimization of an elispot assay to detect cytomegalovirus-specific CD8+ T lymphocytes

Various arguments suggest that CD8+ T lymphocytes play a major role in the control of cytomegalovirus (CMV) infection. The detection of CMV-specific CD8+ T cells may therefore provide additional information about CMV virus detection to predict the risk of development of CMV disease, especially in immunodepressed transplant recipients. We compared and tested various experimental conditions to optimize an enzyme-linked immunospot assay (Elispot) assay for the detection of CMV-specific CD8+ T lymphocytes. The indirect Elispot assay with one six-day in vitro sensitization step was found to be the most sensitive method to detect CMV-specific CD8+ T cells compared to direct Elispot with unfractionated peripheral blood mononuclear cells or purified CD8+ T cells. We showed that low doses of interleukin-2 during the in vitro culture enhanced the sensitivity of this test, and tetramer staining was performed to verify the high efficiency of this in vitro stimulation step. We directly loaded the specific CMV peptide during the Elispot assay and demonstrated that the use of T2 cells did not improve its sensitivity. Elispot for the detection of interferon-gamma appears to be more sensitive and reliable than measurement of tumor necrosis factor alpha or granzyme B. This technique was successfully applied to detect CMV-specific CD8+ T cells in human leukocyte antigen A2 (HLA-A2) and HLA-B7 healthy patients and in one lymphopenic post-transplant patient with positive CMV serology. This highly sensitive test may be a useful tool to assess T-cell immunity directed against CMV in immunodepressed patients.     

Conservative Surgery in T3–T4 Pharyngolaryngeal Squamous Cell Carcinoma: An Alternative to Radiation Therapy and to Total Laryngectomy for Good Responders to Induction Chemotherapy

Objective To evaluate the possibility of preservation of the larynx after neoadjuvant chemotherapy by performing a conservative surgery instead of total laryngectomy initially planned, in patients with previously untreated laryngeal and piriform sinus squamous cell carcinoma (SCC). Study Design Retrospective study. Methods A total of 115 patients treated at Tenon Hospital with induction chemotherapy from 1985 to 1995, all with initial indication of radical surgery, were available for the study. The clinical tumor response was evaluated after three cycles of chemotherapy. According to this response, to preserve laryngeal functions, some patients had a modification of the treatment initially planned: radiation therapy essentially for complete responders, and conservative surgery for some partial responders. Results Of 69 patients with laryngeal cancer, 14 were treated by partial laryngectomy and 19 by radiation therapy; of 46 patients with piriform sinus cancer, 8 were treated by partial surgery and 12 by radiation therapy; the other patients were treated as was initially planned (total laryngectomy with partial pharyngectomy). Overall survival rates, estimated by the Kaplan‐Meier method, were not statistically different between the three treatment groups. The laryngeal functions were preserved in 54% of the patients who were alive at 3 years. Conclusion This report is a retrospective study, but these results suggest the possibility of using conservative surgery, instead of initially planned total laryngectomy, for good responders to induction chemotherapy with a small residual tumor.     

Client-centred practice: what does it mean and does it make a difference?

During the past 15 years, occupational therapists in Canada, through the Canadian Association of Occupational Therapists, have worked to develop and implement guidelines for practice of a client-centred approach to occupational therapy. One of the difficulties with the current Guidelines for the Client-Centred Practice of Occupational Therapy is the lack of a definition and discussion of the concepts and issues fundamental to client-centred practice. In this paper, key concepts of client-centred practice: individual autonomy and choice, partnership, therapist and client responsibility, enablement, contextual congruence, accessibility and respect for diversity are discussed. Two practice examples are used to illustrate these ideas and raise issues about obstacles to the practice of client-centred occupational therapy. Research evidence about the effectiveness of client-centred concepts in enhancing client satisfaction, functional outcomes and adherence to health service programmes is reviewed.     

An epidemiologic case-control study of breast cancer and exposure to hair dyes.

An epidemiologic case-control study of 1617 patients with a primary breast cancer and 1617 control subjects was conducted to test the hypothesis that use of hair dyes is related to breast cancer. No overall association was observed between breast cancer risk and "ever use" of hair dyes (odds ratio, 1.04; 95% confidence interval, 0.90 to 1.21), age when hair dye use started and age when it stopped, duration of hair dye use (years), types of hair dyes used, and estimated lifetime number of individual applications. The current data set also failed to show an increased risk for breast cancer in women who had been diagnosed with benign breast disease and were exposed to hair dyes.     

Cannabinoid hyperemesis syndrome in two French emergency departments: a prospective cohort

Chronic cannabis use can be associated with uncontrollable vomiting and abdominal pain. Diagnostic criteria for cannabinoid hyperemesis syndrome (CHS) were defined in 2012 by Simonetto et al. The objectives of this study were to describe the prevalence of CHS, the patients' epidemiological characteristics, and to show the difficulties encountered in caring for these patients in emergency departments, the extent of health care and an unsuitable follow‐up in general practices. A prospective cohort of patients with CHS was recruited among a target population of patients leaving the adult emergency services of the Marseille hospitals Nord and La Timone between October 2017 and July 2018, with abdominal pain syndrome of unidentified etiology. Inclusion criteria for the CHS cohort were chronic cannabis use associated with nausea and vomiting. There were 48 patients included in the CHS cohort who took cannabis daily, in a target population of 2 848 patients (i.e. 1.6%). A hot shower was the most effective symptomatic treatment in 54.2% of cases. Patients suffering from CHS spent significantly more hours in emergency departments (11 vs. 6.5), and, on average, visits were more frequent (4.9 vs. 3). 20.3% of them were hospitalized to continue pain medication. Once out of hospital, follow‐up was limited, and weaning off cannabis, the only etiological treatment, was difficult to set up. Informing patients about CHS is essential, and a hot shower could be systematically proposed, thus limiting an unnecessary extent of health care. CHS is genuine, medical staff should be made aware of it in occupational training, and it should be seriously considered in health policies.