Therapy-Related Acute Promyelocytic Leukemia: A Case Report and a Review of Literature.

Acute promyelocytic leukemia (APL) is a subgroup of acute myeloid leukemia (AML), and while not a common form of cancer, it does make up a modest portion of acute leukemia. The genetic hallmark of APL is the t(15;17)(q24.1;q21.2) promyelocytic leukemia/retinoic acid receptor alpha (PML/RARA) protein. We present the case of a patient who had undergone prior therapy for stage IIIC squamous cell carcinoma of the anorectal region with 5-fluorouracil, mitomycin C, and radiation and developed therapy-related acute promyelocytic leukemia about 18 months later. We also review the clinical features and management of APL while also highlighting that therapy-related APL, although uncommon, can develop from chemoradiation. The specific diagnosis of therapy-related APL is its own distinct diagnosis, but its treatment remains the same as primary APL.

An Etiological Investigation of Paraneoplastic Cerebellar Degeneration in Ovarian Cancer Patients: A Systematic Review.

Paraneoplastic syndromes (PNS) are uncommon, distinct clinical complications of a primary tumor. Paraneoplastic cerebellar degeneration (PCD) is a PNS that is described as an autoimmune response targeting Purkinje cells in the cerebellum. Ovarian cancer (OC) is one of the most prevalent causes of cancer-related deaths in women. Anti-Yo is the most common onconeural antibody produced in the PCD immune response and is most typically found in ovarian and breast cancer patients. While the current literature highlights the predisposing genetic factors, diagnostic workflows, and treatment options, the pathophysiology of PCD, among other considerations, remains largely unestablished. This review aimed to systematically observe procedural solutions to facilitate an early diagnosis and improve the prognosis of patients with OC-associated PCD. To that end, we examined literature published from 01/01/2015-11/10/2022 indexed in PubMed by using the keywords "paraneoplastic, cerebellar degeneration" combined with "ovarian cancer." Inclusion criteria were met if PCD and OC diagnoses were made and if studies provided adequate patient information. After screening and assessing records for eligibility using the inclusion and exclusion criteria, 18 articles involving 102 patients were included. The typical patient observed in this sample was diagnosed with International Federation of Gynecology and Obstetrics (FIGO) Stage III, high-grade serous carcinoma. The diagnostic workup typically included a clinical evaluation for dysarthria (50%), ataxia (60%), and gait abnormalities (50%), along with multiple imaging modalities and serological findings (90%). Genetic screening for human leukocyte antigen (HLA) haplotype susceptibility for PCD and immune tolerance modulators regulation may also be recommended prior to starting treatment. Findings support the use of corticosteroids (35%) and intravenous immunoglobulin (IVIg) (40%) as viable treatment options for managing PCD in conjunction with systemic therapy for the primary malignancy. A diagnosis of PCD should be considered if a patient has had a malignancy in the past five years with the presence of explicit cerebellar symptoms. This clinical diagnosis can be further supplemented by serologic and radiologic findings. Recognizing PCD symptoms and scheduling genetic and proteomic testing may help with early diagnosis and better prognosis.

Metastatic BRAF V600E-Mutated Adenocarcinoma of the Lung Presenting as Extreme Neutrophilia and Eosinophilia.

Hematologic paraneoplastic syndromes with extreme neutrophilia and eosinophilia are very rarely associated with adenocarcinoma of the lung. We describe a case of a 57-year-old female who presented with neutrophil- and eosinophil-predominant hyperleukocytosis and hypoxic respiratory insufficiency. Bone marrow biopsy confirmed metastatic adenocarcinoma, similar to the biopsy-proven adenocarcinoma of the lung. She was administered one dose of cytotoxic chemotherapy with carboplatin and pemetrexed and started on leukoreductive therapy with hydroxyurea. Molecular testing revealed a BRAF V600E mutation and she was started on dabrafenib and trametinib with significant clinical improvement. This is the first reported case of metastatic BRAF V600E mutated non-small cell lung cancer presenting with extreme neutrophilia and eosinophilia treated with a combination BRAF and mitogen-activated extracellular kinase (MEK) inhibitor.

Assessment and management of advanced adrenocortical carcinoma using a precision oncology care model.

Within the category of orphan diseases and rare malignancies, adrenocortical carcinoma (ACC) represents an aggressive entity with high mortality and morbidity. While localized tumors which are diagnosed early can be cured with surgical intervention, there are prognostic factors which predict for micrometastases and consequent recurrent and advanced disease. In such cases, cytotoxic chemotherapy and mitotane have been utilized with a very modest degree of benefit. The poor prognosis of recurrent and advanced ACC has underscored the interest in nuanced characterization of ACC cases using next-generation sequencing (NGS)-based genomic and other '-omic' profiling to guide the precision medicine approach and personalized use of targeted and novel therapies.

Practice innovation: the need for nimble data platforms to implement precision oncology care.

Given the drive toward personalized, value-based, and coordinated cancer care delivery, modern knowledge-based practice is being shaped within the context of an increasingly technology-driven healthcare landscape. The ultimate promise of 'precision medicine' is predicated on taking advantage of the range of new capabilities for integrating disease- and individual-specific data to define new taxonomies as part of a systems-based knowledge network. Specifically, with cancer being a constantly evolving complex disease process, proper care of an individual will require the ability to seamlessly integrate multi-dimensional 'omic' and clinical data. Importantly, however, the challenges of curating knowledge from multiple dynamic data sources and translating to practice at the point-of-care highlight parallel needs. As patients, caregivers, and their environments become more proactive in clinical care and management, practical success of precision medicine is equally dependent on the development of proper infrastructures for evolving data integration, platforms for knowledge representation in a clinically-relevant context, and implementation within a provider's work-life and workflow.