Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group.

Cancer immunotherapy has transformed the treatment of cancer. However, increasing use of immune-based therapies, including the widely used class of agents known as immune checkpoint inhibitors, has exposed a discrete group of immune-related adverse events (irAEs). Many of these are driven by the same immunologic mechanisms responsible for the drugs' therapeutic effects, namely blockade of inhibitory mechanisms that suppress the immune system and protect body tissues from an unconstrained acute or chronic immune response. Skin, gut, endocrine, lung and musculoskeletal irAEs are relatively common, whereas cardiovascular, hematologic, renal, neurologic and ophthalmologic irAEs occur much less frequently. The majority of irAEs are mild to moderate in severity; however, serious and occasionally life-threatening irAEs are reported in the literature, and treatment-related deaths occur in up to 2% of patients, varying by ICI. Immunotherapy-related irAEs typically have a delayed onset and prolonged duration compared to adverse events from chemotherapy, and effective management depends on early recognition and prompt intervention with immune suppression and/or immunomodulatory strategies. There is an urgent need for multidisciplinary guidance reflecting broad-based perspectives on how to recognize, report and manage organ-specific toxicities until evidence-based data are available to inform clinical decision-making. The Society for Immunotherapy of Cancer (SITC) established a multidisciplinary Toxicity Management Working Group, which met for a full-day workshop to develop recommendations to standardize management of irAEs. Here we present their consensus recommendations on managing toxicities associated with immune checkpoint inhibitor therapy.

BRAF inhibitors: experience in thyroid cancer and general review of toxicity.

The US Food and Drug Administration-approved BRAF inhibitors, vemurafenib and dabrafenib, have demonstrated superior efficacy in patients with BRAF-mutant melanomas but have limited efficacy in BRAF-mutant colorectal cancer. Little is known at this time regarding BRAF inhibitors in thyroid cancer. Initial reports in patients with progressive, radioactive iodine-refractory BRAF-mutant papillary thyroid cancer suggest response rates of approximately 30-40%. In this review, we discuss BRAF inhibitors in the context of thyroid cancer, the toxicities associated with BRAF inhibitors, and the suggested management of those toxicities. The management of vemurafenib and dabrafenib toxicities is applicable across all tumor types and may serve as a practical guide to their use.

The use of complementary and alternative therapies and of psychotherapy by Romanian patients with irritable bowel syndrome.

UNLABELLED: Irritable bowel syndrome (IBS) is an invalidating condition, lacking a perfect therapy. Therefore, many patients use also complementary and alternative therapies (CAT) or psychotherapy (PT). There are no data on the use of CAT and PT in IBS in our area. We looked for this until uncovered aspect of IBS management in Romania. MATERIAL AND METHODS: 250 consecutive patients with IBS (142 F/108M, aged 49 +/- 12 years) referred to a tertiary gastroenterological center were questioned about the use of CAT and PT using a structured specially developed questionnaire. All of the patients accepted to answer the questionnaire after careful instruction. RESULTS: 162 out of 250 pts (64%) admitted to have used one or more CAT, usually together with pharmacological prescriptions. Among CAT users, 32 patients (20%) used only CAT and not allopathic drugs. CAT used were: homeopathy 13%, herbal therapy 72%, acupuncture 3%, bioenergetic resonance 11%, others 13%. Probiotics were used by 30%. Users were mainly females of lower educational levels. Psychotherapy was used by 30 pts (12%). 25 (10%) used CBT, 15 (6%) used relaxation therapy. CONCLUSION: The majority of IBS pts. in our area use CAT usually in association with allopathic therapy. The most frequently used are herbal prescriptions followed by probiotics. PT less frequently used in our IBS patients.

Optimizing therapy for radioactive iodine-refractory differentiated thyroid cancer: current state of the art and future directions.

The majority of patients with differentiated thyroid cancer are cured with standard primary treatments including surgery, radioactive iodine and TSH suppression. A small proportion of patients who develop radioactive iodine-refractory metastatic disease have few treatment options. Recent discovery of the molecular mechanisms that contribute to thyroid cancer tumorigenesis and its progression have revealed key targets that are currently being evaluated in clinical trials. In the last decade several novel targeted therapies have shown encouraging results and have brought hope to patients with advanced disease. However, identifying the subpopulation of patients who may benefit from systemic therapies remains a challenge as the use of these therapeutic modalities is associated with high toxicity rates and most patients have a long indolent phase where the tumor is stable or slowly progressive and asymptomatic. The objective of this review is to summarize the management of patients with metastatic, radioactive iodine refractory differentiated thyroid cancer.