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Therapeutic cancer vaccines have shown activity in metastatic castration-resistant prostate cancer (mCRPC), and methods are being assessed to enhance their efficacy. Ipilimumab is an antagonistic monoclonal antibody that binds cytotoxic T-lymphocyte-associated protein 4, an immunomodulatory molecule expressed by activated T cells, and to CD80 on antigen-presenting cells. We aimed to assess the safety and tolerability of ipilimumab in combination with a poxviral-based vaccine targeting prostate-specific antigen (PSA) and containing transgenes for T-cell co-stimulatory molecule expression, including CD80. We did a phase 1 dose-escalation trial, with a subsequent expansion phase, to assess the safety and tolerability of escalating doses of ipilimumab in combination with a fixed dose of the PSA-Tricom vaccine. Patients with mCRPC received 2×108 plaque-forming units of recombinant vaccinia PSA-Tricom subcutaneously on day 1 of cycle 1, with subsequent monthly boosts of 1×109 plaque-forming units, starting on day 15. Intravenous ipilimumab was given monthly starting at day 15, in doses of 1, 3, 5, and 10 mg/kg. Our primary goal was to assess the safety of the combination. This study is registered with ClinicalTrials.gov, number NCT00113984. We completed enrolment with 30 patients (24 of whom had not been previously treated with chemotherapy) and we did not identify any dose-limiting toxic effects. Grade 1 and 2 vaccination-site reactions were the most common toxic effects: three of 30 patients had grade 1 reactions and 26 had grade 2 reactions. 21 patients had grade 2 or greater immune-related adverse events. Grade 3 or 4 immune-related adverse events included diarrhoea or colitis in four patients and grade 3 rash (two patients), grade 3 raised aminotransferases (two patients), grade 3 endocrine immune-related adverse events (two patients), and grade 4 neutropenia (one patient). Only one of the six patients previously treated with chemotherapy had a PSA decline from baseline. Of the 24 patients who were chemotherapy-naive, 14 (58%) had PSA declines from baseline, of which six were greater than 50%. The use of a vaccine targeting PSA that also enhances co-stimulation of the immune system did not seem to exacerbate the immune-related adverse events associated with ipilimumab. Randomised trials are needed to further assess clinical outcomes of the combination of ipilimumab and vaccine in mCRPC. US National Institutes of Health.

CLINICAL PRACTICE POINTS ● Co-existence of breast cancer and lymphoma is a rare condition. A few cases of synchronous breast ductal carcinoma and lymphoma have been reported in the literature. However, to our knowledge this is the first case report of a bilateral breast lobular carcinoma co-presenting with follicular lymphoma. ● Little is known about the pathophysiology of synchronous cancers of different tumor types, especially solid tumors co-existing with hematologic malignancies. In-depth review of these cases can shed light on underlying mechanism leading to synchronous cancer development.

Opinion statement Immune therapies represent a quantum leap in the fight against cancer. Recently approved immune checkpoint inhibitors that target receptors involved in immune escape of cancer cells (including cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein-1 (PD-1), and programmed cell death protein ligand-1 (PD-L1) are increasingly being used for therapeutic benefit in a number of cancers. The robust anti-cancer activity of these agents has been accompanied by the recognition of new adverse effects, often due to the over activation of immune system, that may limit their therapeutic benefit and adversely impact outcomes. Combination treatments in particular, such as approaches using two targeted immunotherapy agents, have higher risk of adverse effects. Our review focuses on the approved checkpoint inhibitor therapies and their potential for cardiovascular toxicity. While very few cases of autoimmune cardiotoxicity and myocarditis have been reported in clinical trials, severe, life-threatening episodes of heart failure and hemodynamic compromise associated with the use of immune checkpoint inhibitors have recently been reported in the literature. Early recognition, diagnosis, and management of autoimmune myocarditis represent an important clinical challenge with no current guidelines available for prevention, identification, and treatment of this serious condition. This area of cardio-oncology is evolving rapidly as more drugs in this class are being discovered and pending approval. There is a need for future studies focused on prospective identification of biomarkers and clinical standards for treatment and long-term follow-up of cardiovascular toxicity to successfully continue the treatment of cancer while preventing the adverse outcomes with novel immune therapies.

The field of therapeutic cancer vaccines is currently in a state of active preclinical and clinical investigation, and certain novel therapies involving tumor immunotherapy have recently come to the forefront of prostate cancer research. While no therapeutic cancer vaccine has yet been approved by the US FDA, recent findings have demonstrated that new paradigms of combination therapies involving vaccines, employed in clinical trials with appropriate design and end points, may ultimately lead to cancer vaccines being used to treat various malignancies. Several characteristics of prostate cancer make it an ideal target for immunotherapy. Its relative indolence allows sufficient time to generate immune responses, which usually take weeks or months to mount. In addition, prostate cancer-associated antigens direct the immune response to prostate cancer cells, thus sparing normal tissue. This review focuses on the future of promising new vaccines and novel perspectives in the treatment of prostate cancer.

Thrombocytopenia can be seen in about 20-25% of patients with bacterial infective endocarditis (IE). Platelets have a major role in the pathogenesis of endocarditis, and they are also sensitive monitors of systemic host response to bacteremia. Thrombocytopenia on presentation of patients with IE identifies higher risk groups and carries higher mortality risk. The presence of thrombocytopenia is an independent prognosticator of poor outcomes in IE. We present a case of a 40-year-old male with the history of injection drug use who was diagnosed with IE and was found to have severe thrombocytopenia on admission was treated with intravenous antibiotics, which dramatically improved his platelet counts as well without any need for plasmapheresis or platelet transfusions.

Purpose To assess whether crofelemer would prevent chemotherapy-induced diarrhea (CID) diarrhea in patients with HER2-positive, any-stage breast cancer receiving trastuzumab (H), pertuzumab (P), and a taxane (T; docetaxel or paclitaxel), with/without carboplatin (C; always combined with docetaxel rather than paclitaxel). Methods Patients scheduled to receive ≥ 3 consecutive TCHP/THP cycles were randomized to crofelemer 125 mg orally twice daily during chemotherapy cycles 1 and 2 or no scheduled prophylactic medication (control). All received standard breakthrough antidiarrheal medication (BTAD) as needed. The primary endpoint was incidence of any-grade CID for ≥ 2 consecutive days. Secondary endpoints were incidence of all-grade and grade 3/4 CID by cycle/stratum; time to onset and duration of CID; stool consistency; use of BTAD; and quality of life (Functional Assessment of Chronic Illness Therapy for Patients With Diarrhea [FACIT-D] score). Results Fifty-one patients were randomized to crofelemer ( n  = 26) or control ( n  = 25). There was no statistically significant difference between arms for the primary endpoint; however, incidence of grade ≥ 2 CID was reduced with crofelemer vs control (19.2% vs 24.0% in cycle 1; 8.0% vs 39.1%, in cycle 2). Patients receiving crofelemer were 1.8 times more likely to see their diarrhea resolved and had less frequent watery diarrhea. Conclusion Despite the choice of primary endpoint being insensitive, crofelemer reduced the incidence and severity of CID in patients with HER2-positive breast cancer receiving P-based therapy. These data are supportive of further testing of crofelemer in CID. Trial registration Clinicaltrials.gov, NCT02910219, prospectively registered September 21, 2016.

Carcinoid tumors are rare, slow-growing neoplasms of neuroendocrine origin commonly affecting the gastrointestinal or respiratory system. They metastasize to lymph nodes and the liver based on their lymphatic and venous drainage of their tissue of origin. Metastasis to the heart is exceedingly rare accounting for

Introduction Programmed cell death-1 (PD-1) checkpoint inhibitors are immunotherapeutic agents that are used to treat advanced malignancies including breast cancer. The adverse effects of these medications include thyroid and pituitary dysfunction and may be treated with glucocorticoids, which may cause steroid-induced effects such as hyperglycemia, osteoporosis, and adrenal suppression. The Common Terminology Criteria for Adverse Events (CTCAE) widely used by oncologists for management can support treatment decisions by endocrinologists in patients undergoing treatment with PD-1 checkpoint inhibitors. Case Description A 42-year-old female with stage IIIc high-grade triple negative left breast invasive ductal carcinoma was started on pembrolizumab immunotherapy (PD-1 inhibitor). Prior to starting treatment, the patient's thyroid function tests were normal: free T4 0.93 ng/dL (normal range [NR] 0.89-1.76 ng/dL) and thyroid-stimulating hormone (TSH) 1.42 uIU/mL (NR 0.55-4.78 uIU/mL). Two weeks later, she developed heat intolerance, diarrhea, weight loss, and dysphagia. At that time, thyroid tests were consistent with thyrotoxicosis with elevated total T3 644.6 ng/dL (NR 60-180 ng/dL) and totalT4 >12. 00 ng/dL with suppressed TSH 0. 01 uIU/mL. Despite negative TSH receptor antibody and thyroid-stimulating immunoglobulin, CT scan of the neck showed diffuse enlargement of the thyroid gland and thickening of the extraocular muscles. On physical examination she had mild exophthalmos. The etiology of thyrotoxicosis was initially thought to be Graves’ disease, but thyroiditis could not be ruled out. Treatment with methimazole and beta blockers was initiated. Three weeks after methimazole was started, her symptoms improved significantly, with repeat thyroid function tests: TSH 3.64 uIU/mL and free T4 1.29 ng/dL. Methimazole was held. Four weeks later, the second dose of pembrolizumab was administered. Later that day, repeat thyroid function tests showed high TSH 53.12 uIU/ml, and low T4 0.55 ng/dL with negative thyroid-stimulating immunoglobulin and thyroid peroxidase antibodies, consistent with thyroiditis. Endocrinology and Oncology teams discussed the CTCAE determining that the severity of thyroiditis was grade 2 (moderate symptoms, able to perform activities of daily living, TSH persistently above 10 uIU/L). Pembrolizumab was continued and hypothyroidism was treated with levothyroxine. Discussion CTCAE is used by oncologists to aid in treatment decisions in patients treated with PD-1 inhibitors. Endocrinologists should consider using the CTCAE grading (severity) scale for each adverse event. Adoption and utilization of the CTACE severity scale by endocrinologists may lead to a more standardized and systematic approach for treatment of thyroid disorders associated with PD-1 inhibitor immunotherapy Presentation: No date and time listed

H. pylori is now a known cause of gastric and duodenal ulcers, noncardia gastric cancer and gastric MALT lymphoma. In addition, the role of this microorganism in causing or preventing a large number of other diseases has been investigated, some of which include esophageal cancer, functional dyspepsia, gastroesophageal reflux disease, asthma, cardiovascular diseases, iron deficiency anemia and idiopathic thrombotic purpura. This article reviews the evidence for these associations and provides suggestions for further research.