Difficulties in Defining Oligometastatic Prostate Cancer: Implications for Clinical Trial Accrual and Community Practice Adoption of Metastasis-Directed Therapy Approaches.

BACKGROUND: Metastasis-directed therapy is widely utilized for oligometastatic prostate cancer patients, but standard imaging does not always identify metastases definitively and, even with PSMA PET, there may be equivocal findings. Not all clinicians have access to detailed imaging review, particularly outside of academic cancer centers, and PET scan access is also limited. We sought to understand how imaging interpretation impacted recruitment to a clinical trial for oligometastatic prostate cancer. METHODS: IRB approval was obtained to review medical records from all patients screened for the institutional IRB-approved clinical trial for men with oligometastatic prostate cancer involving androgen deprivation plus stereotactic radiation to all metastatic sites, as well as radium223 (NCT03361735). Clinical trial inclusion required at least one bone metastatic lesion and no more than five total sites of metastasis, including soft tissue sites. Tumor board discussion records were reviewed, along with results from additional radiology studies ordered or confirmatory biopsies performed. Clinical characteristics such as PSA level and Gleason score were studied for association with likelihood of oligometastatic disease confirmation. RESULTS: At the time of data analysis, 18 subjects were deemed eligible and 20 were not eligible. The most common reasons for ineligibility were no confirmed bone metastasis in 16 patients (59%) and too many metastatic sites in 3 (11%). The median PSA of eligible subjects was 3.28 (range 0.4-45.5), whereas the median PSA of those found to be ineligible was 10.45 (range 3.7-26.3) when there were too many metastases identified, and 2.7 (range 0.2-34.5) when metastases were unconfirmed. PET imaging (PSMA or fluciclovine PET) increased the number of metastases, while MRI resulted in downstaging to non-metastatic disease. CONCLUSIONS: This research suggests that additional imaging (i.e., at least two independent imaging modalities of a possible metastatic lesion) or tumor board adjudication of imaging findings may be critical to correctly identify patients appropriate for enrollment in oligometastatic protocols. This should be considered as trials of metastasis-directed therapy for oligometastatic prostate cancer accrue and results are translated to broader oncology practice.

Small Cell Lung Cancer from Traditional to Innovative Therapeutics: Building a Comprehensive Network to Optimize Clinical and Translational Research.

Small cell lung cancer (SCLC) is an aggressive, complex disease with a distinct biology that contributes to its poor prognosis. Management of SCLC is still widely limited to chemotherapy and radiation therapy, and research recruitment still poses a considerable challenge. Here, we review the current standard of care for SCLC and advances made in utilizing immunotherapy. We also highlight research in the development of targeted therapies and emphasize the importance of a team-based approach to make clinical advances. Building an integrative network between an academic site and community practice sites optimizes biomarker and drug target discovery for managing and treating a difficult disease like SCLC.

Unusual case of dasatinib-associated acute bilateral hyphemas leading to blindness in a patient with chronic myeloid leukaemia.

Chronic myeloid leukaemia (CML) is a myeloproliferative disorder with an incidence of 1-2 cases per 100 000 adults per year.1 Since the International Randomized Study of Interferon and STI571 trial (IRIS trial) in 2003, treatment with tyrosine kinase inhibitors (TKIs) has become the standard of care for patients with newly diagnosed CML in the chronic phase.2 Dasatinib is a second-generation TKI and is generally well tolerated, with cytopenias, gastrointestinal (GI) symptoms and fluid retention being the most commonly observed side effects.3-5 Bleeding complications, although unusual, have been reported with dasatinib, with an incidence ranging from 8% to 24%.3-6 The most commonly reported site of bleeding is the GI tract.3 5 We report an unusual case of dasatinib-associated bleeding presenting with acute bilateral hyphemas, which, to our knowledge, is the first report of its kind.

Metastatic squamous cell carcinoma of colon from esophageal cancer.

BACKGROUND: Esophageal cancer including squamous cell carcinoma (SCC) and adenocarcinoma represents 4% of all cancers in the United States. Patients with esophageal cancer frequently present with locally advanced disease, and about 40% of patients have evidence of metastatic disease on presentation. Common sites of metastasis include liver, lung and bone. Here, we present a rare case of colonic metastasis from primary esophageal SCC. CASE PRESENTATION: A 60-year-old Caucasian male with a history of 20-pack-year cigarette smoking received surgery and adjuvant chemoradiotherapy for locally advanced SCC of larynx. Approximately 9 months later, he developed dysphagia, and found to have a esophageal SCC in the mid-esophagus with regional lymph node involvement. He underwent chemoradiation treatment with good response and improved symptoms but declined subsequent surgical resection for esophageal cancer. About 1 year after the diagnosis of esophageal cancer, he developed blood streaked bowel movement and severe anemia. Colonoscopy showed a 3-cm mass in the proximal ascending colon; biopsy showed metastatic SCC, consistent with metastasis from esophageal primary. He subsequently received palliative radiation to the ascending colon metastatic tumor with improvement of anemia, and remained transfusion independent for more than 3 months. CONCLUSIONS: Colonic metastasis from esophageal SCC is rare, and associated with poor prognosis. There are no definite features in terms of location, histological differentiation etc. that contribute to colonic metastasis from primary esophageal SCC. The goal of treatment is palliative and data from our and other case reports support the use of chemotherapy and radiation for symptom improvement and disease control.

Home-based diagnosis of obstructive sleep apnea in an urban population.

STUDY OBJECTIVES: Home-based diagnosis of obstructive sleep apnea (OSA) with portable monitoring (PM) is increasingly utilized, but remains understudied in underserved and minority populations. We tested the feasibility of home PM in an urban population at risk for OSA compared to in-laboratory polysomnography (PSG) and examined patient preference with respect to home PM versus PSG. METHODS: Randomized crossover study of home PM (WatchPAT200) and in-laboratory simultaneous PSG and PM in 75 urban African Americans with high pre-test probability of OSA, identified with the Berlin questionnaire. RESULTS: Fifty-seven of 75 participants were women, average age 45 ± 11 years (mean ± SD), 35% with ≤ high school education, and 76% with annual household income < $50,000. Technical failure rates were 5.3% for home vs. 3.1% for in-laboratory PM. There was good agreement between apnea hypopnea index on PSG; AHIPSG and AHI on home PM (mean ± 2 SD of the differences = 0.64 ± 46.5 and intraclass correlation coefficient; ICC = 0.73). The areas under the curve for the receiver-operator characteristic curves for home PM were 0.90 for AHIPSG ≥ 5, 0.95 for AHIPSG ≥ 10, and 0.92 for AHIPSG ≥ 15. 62/75 (82%) participants preferred home over in-laboratory testing. CONCLUSIONS: Home PM for diagnosis of OSA in a high risk urban population is feasible, accurate, and preferred by patients. As home PM may improve access to care, the cost-effectiveness of this diagnostic strategy for OSA should be examined in underserved urban and rural populations. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov, identifier: NCT01997723.

Fine needle aspiration cytology in lesions of oral and maxillofacial region: Diagnostic pitfalls.

BACKGROUND: Fine needle aspiration cytology (FNAC) of oral and maxillofacial region has not been widely utilized for diagnosis due to diversity of lesion types, heterogeneity of cell populations and difficulties in reaching and aspirating these lesions. AIM: Our aim was to demonstrate the effectiveness of this cheap and simple procedure for the diagnosis of tumor and tumor like lesions of oral and maxillofacial region. In addition, we sought to highlight probable causes of errors in the cases showing lack of correlation between cytological and histological diagnoses. MATERIALS AND METHODS: The study was conducted on 50 patients of all age groups with various palpable lesions in the oromaxillofacial region. A comparison between cytological and histological diagnosis was done wherever biopsy material was available. RESULTS: The rate of unsatisfactory FNA was 4%. There were six false negative cases but no false positive case. The sensitivity of our study ranged from 77.7 to 75% including and excluding the suspicious cases, respectively. Specificity and positive predictive value was 100%. CONCLUSION: FNAC is a minimally invasive, highly accurate and cost-effective procedure for the assessment of patients with oromaxillofacial lesions. When applied in a proper manner, FNAC can help avoid a surgical biopsy in many cases.

Synaptic and morphological neuroadaptations in the putamen associated with long-term, relapsing alcohol drinking in primates.

Alcoholism and alcohol use disorders are characterized by several months to decades of heavy and problematic drinking, interspersed with periods of abstinence and relapse to heavy drinking. This alcohol-drinking phenotype was modeled using macaque monkeys to explore neuronal adaptations in the striatum, a brain region controlling habitual behaviors. Prolonged drinking with repeated abstinence narrowed the variability in daily intake, increased the amount of ethanol consumed in bouts, and led to higher blood ethanol concentrations more than twice the legal intoxication limit. After the final abstinence period of this extensive drinking protocol, we found a selective increase in dendritic spine density and enhanced glutamatergic transmission in the putamen, but not in the caudate nucleus. Intrinsic excitability of medium-sized spiny neurons was also enhanced in the putamen of alcohol-drinking monkeys in comparison with non-drinkers, and GABAeric transmission was selectively suppressed in the putamen of heavy drinkers. These morphological and physiological changes indicate a shift in the balance of inhibitory/excitatory transmission that biases the circuit toward an enduring increase in synaptic activation of putamen output as a consequence of prolonged heavy drinking/relapse. The resultant potential for increased putamen activation may underlie an alcohol-drinking phenotype of regulated drinking and sustained intoxication.