Fertility outcomes post immune checkpoint inhibitor exposure.

Harrold et al. evaluate the fertility impact of checkpoint inhibitor blockade (ICB), demonstrating that unlike in utero exposure, post-exposure conception appears to result in uncomplicated pregnancies and healthy progeny. They demonstrate contemporaneous monitoring of temporal female hormonal fluctuations before, on, and post ICB exposure and prior to successful embryo implantation.

Use of real-time respiratory function monitor improves neonatal face mask ventilation: Cross-over simulation study.

Background: Neonatal resuscitation airway training can be difficult as there is no feedback on the face mask technique. "JUNO" is a training respiratory function monitor that provides feedback on mask leak, ventilatory rate, and tidal volume.

Objective: To evaluate whether the use of the JUNO improves face mask ventilation techniques in manikin models.

Immune checkpoint inhibitor therapy in locally advanced MSI GI malignancies.

Locally advanced gastrointestinal (GI) malignancies have conventionally been treated in a multimodal fashion that combines (neo)adjuvant chemotherapy with or without radiation and definitive surgical resection. Clinical data have demonstrated the reduced responsiveness of GI malignancies with microsatellite instability (MSI) to both adjuvant and neoadjuvant systemic chemotherapy when compared with microsatellite stable (MSS) disease. The elevated tumor mutational burden associated with MSI tumors of all types sensitizes these tumors to the effects of immune checkpoint blockade in the metastatic setting, which led to tumor-agnostic approval of immune checkpoint inhibitors in this context.

Precision medicine for pancreatic cancer: characterizing the clinicogenomic landscape and outcomes of KRAS G12C-mutated disease.

Background: Mutated Kirsten rat sarcoma viral oncogene homolog (KRAS) is the most common oncogene alteration in pancreatic ductal adenocarcinoma, and KRAS glycine to cystine substitution at codon 12 (G12C) mutations (KRAS G12Cmut) are observed in 1%-2%. Several inhibitors of KRAS G12C have recently demonstrated promise in solid tumors, including pancreatic cancer. Little is known regarding clinical, genomics, and outcome data of this population.

Molecular and Clinical Determinants of Acquired Resistance and Treatment Duration for Targeted Therapies in Colorectal Cancer.

Purpose: Targeted therapies have improved outcomes for patients with metastatic colorectal cancer, but their impact is limited by rapid emergence of resistance. We hypothesized that an understanding of the underlying genetic mechanisms and intrinsic tumor features that mediate resistance to therapy will guide new therapeutic strategies and ultimately allow the prevention of resistance.

Experimental Design: We assembled a series of 52 patients with paired pretreatment and progression samples who received therapy targeting EGFR (n = 17), BRAF V600E (n = 17), KRAS G12C (n = 15), or amplified HER2 (n = 3) to identify molecular and clinical factors associated with time on treatment (TOT).

Upper Gastrointestinal Cancers and the Role of Genetic Testing.

Beyond the few established hereditary cancer syndromes with an upper gastrointestinal cancer component, there is increasing recognition of the contribution of novel pathogenic germline variants (gPVs) to upper gastrointestinal carcinogenesis. The detection of gPVs has potential implications for novel treatment approaches of the index cancer patient as well as long-term implications for surveillance and risk-reducing measures for cancer survivors and far-reaching implications for the patients' family. With widespread availability of multigene panel testing, new associations may be identified with germline-somatic integration being critical to determining true causality of novel gPVs.

Neoplasia risk in patients with Lynch syndrome treated with immune checkpoint blockade.

Metastatic and localized mismatch repair-deficient (dMMR) tumors are exquisitely sensitive to immune checkpoint blockade (ICB). The ability of ICB to prevent dMMR malignant or pre-malignant neoplasia development in patients with Lynch syndrome (LS) is unknown. Of 172 cancer-affected patients with LS who had received ≥1 ICB cycles, 21 (12%) developed subsequent malignancies after ICB exposure, 91% (29/32) of which were dMMR, with median time to development of 21 months (interquartile range, 6-38).

Early-Onset GI Cancers: Rising Trends, Genetic Risks, Novel Strategies, and Special Considerations.

Cancers in young adults (commonly described as early-onset [EO] cancer) represent a group of malignancies that have unique and challenging biology and genetic, treatment, social, and psychological implications. Even more concerning is a rising trend of EO cancers in multiple tumor types. Research and investigation in EO cancers will help elucidate mechanisms of carcinogenesis, differences in biology and response to treatment, and the need for multidisciplinary care to ensure comprehensive treatment and support for young patients.

Targeting MET amplification in Gastro-oesophageal (GO) malignancies and overcoming MET inhibitor resistance: challenges and opportunities.

Introduction: MET, the hepatocyte growth factor receptor is amplified in 8% of gastroesophageal (GO) malignancies and associated with poor prognosis. Therapeutic targeting of MET amplification and MET mutations has the potential to improve outcomes for patients with GO cancers (GOC).

Areas Covered: The efficacy of MET inhibition (METi) in preclinical studies has yet to translate into meaningful improvements in the treatment paradigm for unselected GOC.

DNA Damage Repair Deficiency in Pancreatic Ductal Adenocarcinoma: Preclinical Models and Clinical Perspectives.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide, and survival rates have barely improved in decades. In the era of precision medicine, treatment strategies tailored to disease mutations have revolutionized cancer therapy. Next generation sequencing has found that up to a third of all PDAC tumors contain deleterious mutations in DNA damage repair (DDR) genes, highlighting the importance of these genes in PDAC.

Prevalence of Insomnia in an Oncology Patient Population: An Irish Tertiary Referral Center Experience.

Background: The NCCN Guidelines for Survivorship recommend dedicated sleep assessment. Reported insomnia prevalence in the general Irish population is 6% to 15%. Reported insomnia prevalence internationally among new/recently diagnosed patients with cancer varies from 30.

Similar overall survival with reduced vs. standard dose bevacizumab monotherapy in progressive glioblastoma.

Introduction: Bevacizumab has demonstrated activity in glioblastoma (GBM), but the true benefits and optimal dose-schedule are debated. A lower dose-schedule than standard-dose bevacizumab (10 mg/kg 2-weekly) might offer similar benefits with lower costs. At our Institution, patients are randomly assigned at time of primary diagnosis to Neuro-Oncologists, who have varying practices in terms of bevacizumab dose-schedule upon progression.

Genomic profiling of a dedifferentiated mucosal melanoma following exposure to immunotherapy.

The treatment landscape for metastatic melanoma has been revolutionised by the introduction of immunotherapy and targeted therapies. Despite these advances, some patients exhibit primary or acquired resistance to treatment. We present the case of a resected mucosal melanoma that on relapse underwent transformation to a dedifferentiated state.

Recurrent vulvar melanoma in a patient with neurofibromatosis and gastrointestinal stromal tumour.

We report a case of a 51-year-old woman with neurofibromatosis who presented in 2012 with postmenopausal bleeding. Excision biopsy of a pigmented lesion of the labia minora was consistent with an ulcerated vulvar BRAF wild type malignant melanoma (MM). Initial excision was followed by radical vulvectomy and adjuvant interferon.

Epithelioid Angiomyolipoma - a case report and review of the literature.

Herein we present the case of a 43-year-old female in whom a left renal mass was identified incidentally on imaging performed for staging of a newly diagnosed breast carcinoma. The mass was resected and histologic examination and immunohistochemistry confirmed a diagnosis of epithelioid angiomyolipoma.

βhCG-secreting osteosarcoma.

A 35-year-old woman presented to our institution with tender, right knee swelling. Radiological and pathological work-up revealed metastatic osteosarcoma. Prior to the initiation of chemotherapy, she underwent a routine urine pregnancy test and was surprised with a positive result.

Monitoring Ionizing Radiation Exposure for Cardiotoxic Effects of Breast Cancer Treatment.

Serial assessments of left ventricular ejection fraction (LVEF) are customary in patients with breast cancer receiving trastuzumab. Radionuclide angiography (RNA) is often used; however, a typical monitoring schedule could include 5 scans in a year. We evaluated the proportion of imaging-related ionizing radiation attributable to RNA in 115 patients with breast cancer, from 3 medical centers in the United States, Ireland, and Japan, who completed 12 months of trastuzumab treatment.

Health professionals working with First Nations, Inuit, and Métis consensus guideline.

Objective: Our aim is to provide health care professionals in Canada with the knowledge and tools to provide culturally safe care to First Nations, Inuit, and Métis women and through them, to their families, in order to improve the health of First Nations, Inuit, and Métis.

Evidence: Published literature was retrieved through searches of PubMed, CINAHL, Sociological Abstracts, and The Cochrane Library in 2011 using appropriate controlled vocabulary (e.g.

RETIRED: Health Professionals Working With First Nations, Inuit, and Métis Consensus Guideline.

This document has been archived because it contains outdated information. It should not be consulted for clinical use, but for historical research only. Please visit the journal website for the most recent guidelines.