Assessing fracture risk in early stage breast cancer patients treated with aromatase-inhibitors: An enhanced screening approach incorporating trabecular bone score

AbstractIntroductionAromatase-inhibitors (AIs) are commonly used for treatment of patients with hormone-receptor positive breast carcinoma, and are known to induce bone density loss and increase the risk of fractures. The current standard-of-care screening tool for fracture risk is bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA). The fracture risk assessment tool (FRAX®) may be used in conjunction with BMD to identify additional osteopenic patients at risk of fracture who may benefit from a bone-modifying agent (BMA). The trabecular bone score (TBS), a novel method of measuring bone microarchitecture by DXA, has been shown to be an independent indicator of increased fracture risk. We report how the addition of TBS and FRAX®, respectively, to BMD contribute to identification of elevated fracture risk (EFR) in postmenopausal breast cancer patients treated with AIs.Methods100 patients with early stage hormone-positive breast cancer treated with AIs, no prior BMAs, and with serial DXAs were identified. BMD and TBS were measured from DXA images before and following initiation of AIs, and FRAX® scores were calculated from review of clinical records. EFR was defined as either: BMD ≤−2.5 or BMD between −2.5 and −1 plus either increased risk by FRAX® or degraded microstructure by TBS.ResultsAt baseline, BMD alone identified 4% of patients with EFR. The addition of FRAX® increased detection to 13%, whereas the combination of BMD, FRAX® and TBS identified 20% of patients with EFR. Following AIs, changes in TBS were independent of changes in BMD. On follow-up DXA, BMD alone detected an additional 1 patient at EFR (1%), whereas BMD+ FRAX® identified 3 additional patients (3%), and BMD+FRAX®+TBS identified 7 additional patients (7%).ConclusionsThe combination of FRAX®, TBS, and BMD maximized the identification of patients with EFR. TBS is a novel assessment that enhances the detection of patients who may benefit from BMAs

Multinational Association of Supportive Care in Cancer (MASCC) 2020 clinical practice recommendations for the management of severe dermatological toxicities from checkpoint inhibitors

Immune checkpoint inhibitors (ICIs) frequently result in cutaneous immune-related adverse events (IrAEs). Although the majority of these events are mild-to-moderate in severity, up to 5% are severe, which may lead to morbidity and dose interruption or discontinuation of ICI therapy. In addition, up to 25% of dermatologic IrAEs are corticosteroid-refractory or corticosteroid-dependent. These 2020 MASCC recommendations cover the diagnosis and management of cutaneous IrAEs with a focus on moderate-to-severe and corticosteroid-resistant events. Although the usage of immune-suppressive therapy has been advocated in this setting, there is a lack of randomized clinical trial data to provide a compelling level of evidence of its therapeutic benefit.NIH/NIAMS; the NIH/NCI Cancer Center; the Cancer Association of South Africa (CANSA) and the National Research Foundation (NRF) of South Africa.http://link.springer.com/journal/5202021-08-20hj2020Immunolog

Multinational Association of Supportive Care in Cancer (MASCC) 2020 clinical practice recommendations for the management of immune checkpoint inhibitor endocrinopathies and the role of advanced practice providers in the management of immune-mediated toxicities

Immune checkpoint inhibitors (ICIs) have emerged as the newest pillar of cancer treatment, transforming outcomes in melanoma and showing benefit in a range of malignancies. Immune-mediated toxicities, stemming from increased activity within the T cell lineage, range from asymptomatic or mild complications to those that are fulminant and potentially fatal. Immune-mediated endocrinopathies include hypophysitis, thyroiditis, and insulin-dependent diabetes mellitus. These presentations, which may be vague and non-specific, can be life-threatening if not diagnosed and treated appropriately. This review considers the work-up and management of immune-mediated endocrinopathies and also considers the role of advanced practice practitioners in the management of immune-mediated toxicities. These state-of-the-art MASCC recommendations represent a comprehensive overview of the management and clinical work-up in those in whom the diagnosis should be considered.The Cancer Association of South Africa (CANSA), the National Research Foundation (NRF) of South Africa and the NIH/NCI (Cancer Center Support Grant P30 CA008748).http://link.springer.com/journal/5202021-08-20hj2020Immunolog

Multinational Association of Supportive Care in Cancer (MASCC) 2020 clinical practice recommendations for the management of immune-mediated cardiovascular, rheumatic, and renal toxicities from checkpoint inhibitors

Immune checkpoint inhibitors (ICIs) have emerged as the newest pillar of cancer treatment. Immune-mediated toxicities, stemming from increased activity within the T cell lineage, range from asymptomatic or mild complications to those that are fulminant and potentially fatal. Although they are of variable occurrence, cardiovascular, rheumatic, and renal immune-mediated toxicities are among the most serious of these adverse events. We present MASCC recommendations with respect to the workup and management of cardiovascular, rheumatic, and renal immune-mediated toxicities with a focus on presentations that require treatment with immunomodulating agents.The Cancer Association of South Africa (CANSA), the National Research Foundation (NRF) of South Africa and the NIH/NCI (Cancer Center Support Grant P30 CA008748).http://link.springer.com/journal/5202021-08-20hj2020Immunolog

Desmoplastic Small Round Cell Tumor with Primary Ovarian Involvement: Case Report and Review

Background. Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive, malignant neoplasm that has recently been characterized. It has not been associated with a primary visceral organ. In women, cases are even more rare and often have some ovarian involvement. Case. An 11-year-old girl presented with abdominal pain, nausea, and vomiting. A CT scan revealed a large heterogeneous pelvic mass with cystic components and an 8-cm midabdominal mass. During exploratory laparotomy, the patient was found to have a pelvic mass measuring 12.9 cm replacing normal ovarian tissue. The midabdominal mass was also removed. Pathology, cytology, and immunohistochemistry confirmed a desmoplastic small round cell tumor. Even with aggressive surgical and medical intervention, the patient died 11 months after initial diagnosis. Conclusion. We present a rare small cell tumor that is associated with ovarian involvement. The prognosis in these patients is extremely poor and very few survivals have been reported

Diagnostic Concordance of Cytology and Histology in Samples Obtained via Endoscopic Ultrasound-Guided Fine-Needle Biopsy (EUS-FNB).

Introduction Endoscopic ultrasound (EUS)-guided fine-needle aspiration and biopsy (FNA/FNB) to obtain cytological aspirates and histological core samples, respectively, are the standard of care for diagnosing lesions in/adjacent to the upper/lower gastrointestinal tract. Due to the lack of standardization of tissue processing, it is unclear whether core samples should be sent only for histology (formalin) or cytology (CytoLyt), or both. The aim of this study was to investigate the diagnostic concordance rates between cytology and histology on EUS-FNB core samples. Methods A total of 227 patients underwent EUS-FNB between October-2017 and February-2019 by a single therapeutic endoscopist; 44 core-tissue samples (41 patients) were placed alternately in CytoLyt (cytology) and formalin (histology), with equal passes into each, to best achieve a proportionate sample amount. The patient\u27s demographics, medical history, pertinent imaging, EUS indication/findings were reviewed. Main outcomes included concordance rates between cytology-histology and diagnostic accuracy for malignancy. Results Cytology and histology were discordant in five cases (11.5%); four with negative cytology but a definite diagnosis of malignancy achieved with histology. One case was suspected as neoplasm on cytology but further characterized as benign on histology. Cytology failed to sub-characterize an additional four mass-like pancreatic benign entities, due to inadequate tissue architecture assessment in the CytoLyt sample. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of cytology for diagnosis of malignancy were 87.88% (95%CI: 71.8-96.6), 90.91% (95%CI: 58.7-99.7), 96.67% (95%CI: 81.6-99.4), and 71.43% (95%CI: 49.4-86.4). Discussion We observed 11.5% diagnostic discordance between cytology and histology on EUS-FNB core samples, with histology being superior. Future multicenter prospective randomized studies are needed to establish an accurate and cost-effective diagnostic process

Transsphenoidal Resection of Sellar Tumors Using High-Field Intraoperative Magnetic Resonance Imaging

There has been increasing experience in the utilization of intraoperative magnetic resonance imaging (iMRI) for intracranial surgery. Despite this trend, only a few U.S centers have examined the use of this technology for transsphenoidal resection of tumors of the sella. We present the largest series in North America examining the role of iMRI for pituitary adenoma resection. We retrospectively reviewed our institutional experience of 59-patients who underwent transsphenoidal procedures for sellar and suprasellar tumors with iMRI guidance. Of these, 52 patients had a histological diagnosis of pituitary adenoma. The technical results of this subgroup were examined. A 1.5-T iMRI was integrated with the BrainLAB (Feldkirchen, Germany) neuronavigation system. The majority (94%) of tumors in our series were macroadenomas. Seventeen percent of tumors were confined to the sella, 49% had suprasellar extensions without involvement of the cavernous sinus, 34% had frank cavernous sinus invasion. All patients underwent at least one iMRI, and 19% required one or more additional sets of intraoperative imaging. In 58% of patients, iMRI led to the surgeon attempting more resection. A gross total resection was obtained in 67% of the patients with planned total resections. There was one case of permanent postoperative diabetes insipidus and no other instances of new hormone replacement. In summary, iMRI was most useful for tumors of the sella with and without suprasellar extension where the information from the iMRI extended the complete resection rate from 40 to 72% and 55 to 88%, respectively. As one would expect, it did not substantially increase the rate of resection of tumors with cavernous sinus invasion. Overall, iMRI was particularly useful in guiding resection safely, aiding in clinical decision making, and allowing identification and preservation of the pituitary stalk and normal pituitary gland. Limitations of the iMRI include a need for additional personnel and training as well as additional operative time, which diminishes over time as personnel learn to optimize workflow efficiency. Additional costs are mitigated in part by using the iMRI as an immediate postoperative scan. Other data emerging from our experience suggest that preservation of normal gland and thus avoidance of hypopituitarism may be improved by iMRI use, but longer follow-up periods are required to test this conclusion. iMRI can detect unsuspected complications sooner than routine postoperative imaging, potentially leading to improved outcomes. However, larger studies are needed

Multinational Association of Supportive Care in Cancer (MASCC) 2020 clinical practice recommendations for the management of immune-related adverse events : pulmonary toxicity

The immune checkpoints associated with the CTLA-4 and PD-1 pathways are critical modulators of immune activation. These pathways dampen the immune response by providing brakes on activated T cells, thereby ensuring more uniform and controlled immune reactions and avoiding immune hyper-responsiveness and autoimmunity. Cancer cells often exploit these regulatory controls through a variety of immune subversion mechanisms, which facilitate immune escape and tumor survival. Immune checkpoint inhibitors (ICI) effectively block negative regulatory signals, thereby augmenting immune attack and tumor killing. This process is a double-edged sword in which release of regulatory controls is felt to be responsible for both the therapeutic efficacy of ICI therapy and the driver of immune-related adverse events (IrAEs). These adverse immune reactions are common, typically low-grade and may affect virtually every organ system. In the early clinical trials, lung IrAEs were rarely described. However, with ever-expanding clinical applications and more complex ICI-containing regimens, lung events, in particular, pneumonitis, have become increasingly recognized. ICI-related lung injury is clinically distinct from other types of lung toxicity and may lead to death in advanced stage disease. Thus, knowledge regarding the key characteristics and optimal treatment of lung-IrAEs is critical to good outcomes. This review provides an overview of lung-IrAEs, including risk factors and epidemiology, as well as clinical, radiologic, and histopathologic features of ICI-related lung injury. Management principles for ICI-related lung injury, including current consensus on steroid refractory pneumonitis and the use of other immune modulating agents in this setting are also highlighted.The Cancer Association of South Africa (CANSA), the National Research Foundation (NRF) of South Africa, the NIH/NCI (Cancer Center Support Grant P30 CA008748).http://link.springer.com/journal/5202021-08-20hj2020Immunolog