Clinical factors and association with treatment modalities in patients with breast cancer and brain metastases who develop leptomeningeal metastases.

PURPOSE: Leptomeningeal metastases (LM) are an aggressive complication of metastatic breast cancer (MBC) with brain metastases (BM), with a short survival of weeks to months. Studies suggest that surgical resection of BM may increase the risk of LM, especially in infratentorial metastases. In this retrospective study, we examine this and other factors which may be associated with increased risk of LM. METHODS: A database search at a single institution identified 178 patients with MBC and treated BM between 2007 and 2020. We collected demographic, clinical, radiographic, and other treatment data. LM was diagnosed by cerebrospinal fluid (CSF) cytology, neuroimaging, or both. Cox proportional hazards model was used. RESULTS: After a median follow-up of 8.5 months, 41 out of 178 patients (23%) with BM developed LM. Median time to develop LM was 130 days. Mean age was 51.3 years. The number and size of the BM, hemorrhagic/cystic lesions, progressive/stable systemic disease, and extracranial metastases sites other than liver did not pose a higher risk of LM. Infratentorial lesions (HR = 5.41) and liver metastases (HR = 2.28) had a higher risk of LM. Patients who had any surgery did not have a higher risk for LM (HR 1.13). The LM group had a worse overall survival as compared to the non-LM group. CONCLUSION: Among MBC patients with BM, infratentorial BM and visceral liver lesions increase the risk of LM, whereas local treatment modalities such as surgery and radiation do not. These data imply that local treatment strategy should not differ based on potential risk for LM.

Metastatic triple-negative breast cancer: Established and emerging treatments.

Metastatic triple-negative breast cancer (mTNBC) patients tend to have a poor overall survival. The primary goals of treatment focus on palliation of symptoms and improvement in overall survival (OS). Single-agent sequential chemotherapy with anthracycline or taxane has remained the cornerstone of treatment for many years. The FDA has approved newer agents such as poly-adenosine diphosphate-ribose polymerase (PARP) inhibitors upfront in germline BRCA (gBRCA) 1/2 mutation carriers; atezolizumab and nab-paclitaxel combination frontline in patients with PD-L1 expression > 1%; and sacituzumab govitecan (IMMU-132), an antibody-drug conjugate in heavily pretreated mTNBC patients.

Skeletal metastases in advanced pancreatic ductal adenocarcinoma: a retrospective analysis.

BACKGROUND: Skeletal metastases (SM) in advanced pancreatic ductal adenocarcinoma (PDAC) is an infrequent occurrence that has been previously reported in literature to occur in less than 2.5% of the cases. Complications such as pathological fractures can result in intractable pain, immobilization and a significant deterioration in quality of life. The purpose of this study is to improve the understanding of the increasing incidence of SM and the importance of surveillance and adequate management of SM in these patients. METHODS: A retrospective analysis was conducted using a clinical database at a single tertiary care institution for cancer patients; this included 207 patients with advanced PDAC diagnosed between December 2004 and March 2017 receiving palliative chemotherapy. SM were identified by computerized tomography (CT)/fluorodeoxyglucose positron emission tomography (FDG-PET)/magnetic resonance imaging (MRI). Information regarding demographics, clinical course and date of last follow-up/death were collected. After a median follow-up of 11 months, an analysis was conducted, including a Kaplan-Meier survival analysis. RESULTS: The study included 207 patients; 19 out of 207 patients (9.2%) developed SM; the primary tumor was located in the pancreatic body/tail in 12 out of 19 patients (63.2%). The thoracic and lumbar vertebrae were the most common sites of SM. Other common synchronous sites of metastases included the liver and lung. A majority of the lesions were osteolytic (63.2%). The median time of diagnosis from the initial diagnosis was 2 months (range, 0-60 months). Bone pain was observed as the initial symptom in 7 out of 19 patients (36.8%), 2 out of 19 patients (10.5%) had a pathological fracture and 1 out of 19 patients (5.3%) developed a para-spinal mass causing inferior vena cava compression. The median survival period for patients with SM was 11 months (range, 0-62 months) and for those without SM was 12 months (range, 0-147 months) [hazard ratio (HR) 1.24, 95% confidence interval (CI): 0.66-2.30, P=0.51]. CONCLUSIONS: There has been a challenge with regards to management of the increasing number of patients with SM. Thoracic and lumbar vertebrae are the most common sites and pathological fractures in these sites can be catastrophic. Careful evaluation of skeletal signs and symptoms, early detection and intervention are essential to prevent morbidity and mortality from complications in patients with PDAC and SM.

Radiation therapy in primary mediastinal large B-cell lymphoma treated with DA-R-EPOCH.

DA-R-EPOCH is used in PMBCL due to its good outcomes without radiation. We present three cases that required consolidation with radiation despite using this regimen. More studies are needed before considering DA-R-EPOCH standard of care.

The safety of pembrolizumab in metastatic melanoma and rheumatoid arthritis.

Immunotherapy has been in use for the treatment of melanoma since a very long time, but only recently have the cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody ipilimumab and programmed cell death-1 inhibitors such as nivolimumab and pembrolizumab been shown to induce marked improvements in survival in patients with metastatic melanoma. An important concern arises in terms of the safety of the use of these agents in patients with autoimmune diseases, solid organ transplant recipients on immunosuppression, patients with a history of previous hepatitis B or C, and patients with HIV infections as these patients were excluded from pivotal immunotherapy studies. Here, we report on the safety and efficacy of pembrolizumab in a melanoma patient with multiple medical problems including poorly controlled rheumatoid arthritis and we review the available literature on the use of immunotherapy and autoimmune diseases. The weight of evidence suggests that these patients should be offered the opportunity to benefit from immune check point inhibitors, with drugs targeting programmed cell death-1 being preferred. More research is required to study the long-term effects of immunotherapy on patients with autoimmune diseases.

Synchronous primary adenocarcinoma of the lung and pancreas: a case series and review of the literature.

AIM: The frequency of pancreatic cancer in association with cancer of other organs ranges from 1 to 20%, with the most common ones being gastric, colon, thyroid and genitourinary. The presence of synchronous lung and pancreatic cancers is extremely rare. CASE SERIES: Two patients with extensive smoking history and variable presentations were found to have simultaneous lung and pancreatic masses both lesions being different histologically and on immunohistochemical staining. After individualized treatment plans, the first patient remains free of disease and the second patient is being treated with a palliative intent. CONCLUSION: The early recognition and treatment is important as there exists a significant survival difference in patients who have synchronous primaries as opposed to those with metastatic pancreatic adenocarcinoma.