First Report of Dramatic Tumor Responses with Ramucirumab and Paclitaxel After Progression on Pembrolizumab in Two Cases of Metastatic Gastroesophageal Adenocarcinoma.

Checkpoint inhibitors targeted at programmed cell death-1 receptor (PD-1) and its ligand (PD-L1) can result in significant benefit to a small proportion of patients with cancer, including those with tumors of the stomach and gastroesophageal junction. These drugs are now approved for several solid tumors, including the recent accelerated approval of pembrolizumab for gastroesophageal adenocarcinomas in the third-line setting and beyond based on the KEYNOTE-059 phase II trial. Data are lacking on the efficacy of chemotherapy after progression on PD-1 blockade in metastatic gastroesophageal adenocarcinoma. This report describes the exceptional response of two patients who received ramucirumab plus paclitaxel after progressive disease on pembrolizumab. This early clinical observation suggests that the sequence of administration of PD-1 blockade and chemotherapy may be important in this disease.

Pleural "drop metastases" 21 years after resection of a thymoma.

INTRODUCTION: We describe an unusual case of pleural drop metastases 21 years after complete resection of an encapsulated thymoma in a Southeast Asian patient with myasthenia gravis (MG). METHODS: This investigation includes a case report and brief review of the literature. RESULTS: The patient presented in 2015 with generalized weakness, fatigue, and shortness of breath, but no diplopia, ptosis, dysphagia, or dysarthria. Because these symptoms were atypical for an MG exacerbation, a de-novo work-up was performed. Chest computed tomography (CT) showed numerous pleural nodules ("drop metastases"), and CT-guided biopsy revealed metastatic thymoma. CONCLUSIONS: The average disease-free interval for thymoma ranges from 68 to 86 months. Pleural and mediastinal recurrence are more common than distant hematogenous recurrence. Adverse prognostic factors include an initial higher Masaoka stage, incomplete resection, older age, and pleural or pericardial involvement. Despite apparent complete resection of thymoma, clinicians should remain vigilant for recurrence for as long as 20 years after initial management. Long-term follow-up with radiologic surveillance is recommended. Muscle Nerve 56: 171-175, 2017.

An unusual presentation of hemolytic anemia in a patient with prosthetic mitral valve.

Although rare, periprosthetic valvular regurgitation can cause hemolytic anemia. We present the case of a 63-year-old man who had an unusual presentation of hemolytic anemia due to periprosthetic mitral valve regurgitation (PMVR) in the presence of cold agglutinins. Due to high surgical risk, PMVR was percutaneously closed with three Amplatzer devices under the guidance of three-dimensional transesophageal echocardiography.

Early Outcomes of Patients With Locally Advanced Non-small Cell Lung Cancer Treated With Intensity-Modulated Proton Therapy Versus Intensity-Modulated Radiation Therapy: The Mayo Clinic Experience.

PURPOSE: There are very little data available comparing outcomes of intensity-modulated proton therapy (IMPT) to intensity-modulated radiation therapy (IMRT) in patients with locally advanced NSCLC (LA-NSCLC). METHODS: Seventy-nine consecutively treated patients with LA-NSCLC underwent definitive IMPT (n = 33 [42%]) or IMRT (n = 46 [58%]) from 2016 to 2018 at our institution. Survival rates were calculated using the Kaplan-Meier method and compared with the log-rank test. Acute and subacute toxicities were graded based on Common Terminology Criteria for Adverse Events, version 4.03. RESULTS: Median follow-up was 10.5 months (range, 1-27) for all surviving patients. Most were stage III (80%), received median radiation therapy (RT) dose of 60 Gy (range, 45-72), and had concurrent chemotherapy (65%). At baseline, the IMPT cohort was older (76 vs 69 years, P < .01), were more likely to be oxygen-dependent (18 vs 2%, P = .02), and more often received reirradiation (27 vs 9%, P = .04) than their IMRT counterparts. At 1 year, the IMPT and IMRT cohorts had similar overall survival (68 vs 65%, P = .87), freedom from distant metastasis (71 vs 68%, P = .58), and freedom from locoregional recurrence (86 vs 69%, P = .11), respectively. On multivariate analyses, poorer pulmonary function and older age were associated with grade +3 toxicities during and 3 months after RT, respectively (both P ≤ .02). Only 5 (15%) IMPT and 4 (9%) IMRT patients experienced grade 3 or 4 toxicities 3 months after RT (P = .47). There was 1 treatment-related death from radiation pneumonitis 6 months after IMRT in a patient with idiopathic pulmonary fibrosis. CONCLUSIONS: Compared with IMRT, our early experience suggests that IMPT resulted in similar outcomes in a frailer population of LA-NSCLC who were more often being reirradiated. The role of IMPT remains to be defined prospectively.

Expanding the Spectrum of Radiation Necrosis After Stereotactic Radiosurgery (SRS) for Intracranial Metastases From Lung Cancer: A Retrospective Review.

OBJECTIVE: Radiation therapy (RT) is the primary treatment of intracranial metastasis (ICM) from lung cancer (LC). Radiation necrosis (RN) has been reported post-RT with an incidence of 5% to 24%. We reviewed the spectrum of imaging changes in patients treated with RT for ICM from LC in an effort to identify potential risk factors for RN. METHODS: We reviewed 63 patients with LC and ICM who received RT (radiosurgery [stereotactic radiosurgery] with/without whole brain radiation therapy) at our institution between 2013 and 2018. Data evaluated included demographics, tumor type, ICM burden and location, chemotherapy, surgery, and RT details as well as treatment choices and outcomes. RESULTS: Of the 63 patients, clinical and radiographic criteria for RN were noted in 24 (38%) as early as 2 months and as late as 5 years posttreatment. Six patients required surgical resection due to refractory symptoms revealing pathology-proven RN and occasionally tumor. Patients were significantly more likely to develop RN if they had surgical resection of an ICM (45.8% vs. 20.5%, P=0.05). No differences were found in location, size, or genetic profile of lesions. In total, 80% of patients received treatment for symptoms and/or radiographic change. This was generally a combination of steroids, bevacizumab, laser interstitial thermal treatment, or surgical resection. Most patients required >1 treatment modality. CONCLUSIONS: This review of outcomes of RT for ICM in LC demonstrates a higher rate of RN than previously reported in the literature in those having had a surgical resection plus stereotactic radiosurgery. Our observation of RN as late as 5 years post-RT for ICM necessitates clinician awareness.

A Case Report of Ischemic Stroke in a Patient with Metastatic Gastric Cancer Secondary to Treatment with the Vascular Endothelial Growth Factor Receptor-2 Inhibitor Ramucirumab.

Ramucirumab is an antiangiogenesis agent targeting the vascular endothelial growth factor receptor-2 (VEGFR-2), approved to treat advanced gastric and colon cancer. In clinical trials, it was shown to cause a small increase in arterial thromboembolism compared to placebo, including cerebral and myocardial ischemia, which was not statistically significant. Detailed case reports are lacking and we here present one of the first case reports of stroke secondary to ramucirumab-induced in situ thrombosis.