H. Danish

BRAF inhibitors and radiotherapy for melanoma brain metastases: potential advantages and disadvantages of combination therapy

Melanoma is an aggressive malignancy that frequently spreads to the brain, resulting in rapid deterioration in both quality and quantity of life. Historically, treatment options for melanoma brain metastases (MBM) have predominantly consisted of surgery and radiotherapy. While these options can help provide local control, the majority of patients still develop intracranial progression. Indeed, novel therapeutic options, including molecularly targeted agents and immunotherapy, have improved outcomes and are now changing the role of radiotherapy. Up to 50% of melanomas contain an activating BRAF mutation, resulting in hyperactive cellular proliferation and survival. Drugs that target BRAF have been introduced for the treatment of metastatic melanoma and offer hope in improving disease outcomes; however, many of these trials either excluded or had a limited amount of patients with MBM. Recent studies have revealed that melanoma cell lines become more radiosensitive following BRAF inhibition, thus providing a potential synergistic mechanism when combining BRAF inhibitor (BRAFi) and radiotherapy. However, neurotoxicity concerns also exist with this combination. This article reviews the efficacy and limitations of BRAFi therapy for MBM, describes current evidence for combining BRAFis with radiation, discusses the rationale and evidence for combination modalities, and highlights emerging clinical trials specifically investigating this combination in MBM.

The role of radiotherapy for patients over age 60 with diffuse large B-cell lymphoma in the rituximab era

Abstract The role of consolidative radiotherapy (RT) in patients ≥60 years old with DLBCL in the rituximab era is controversial. We examined the impact on disease control and overall survival by the addition of consolidative RT after completion of chemotherapy, while adjusting for known adverse risk factors. Retrospective chart review from 2004 to 2012 of 83 consecutive patients ≥60 years old with DLBCL treated in the rituximab era, 68 of which had a complete response to chemotherapy, was performed. Amongst patients with a complete response, consolidative RT use was associated with 100% 5-year local control, improved progression-free survival (p = 0.047), and a trend for overall survival (p = .098) on multivariate analysis. Amongst all patients, the use of consolidative RT was associated with improved overall survival (p = 0.03). The use of consolidative RT should be considered for patients ≥60 years old independent of stage and response to chemotherapy.

The influence of postoperative lymph node radiation therapy on overall survival of patients with stage III melanoma, a National Cancer Database analysis

Recently, TROG 02.01 results showed that in stage III melanoma patients with nodal metastasis, adjuvant radiation to lymph node basin after nodal dissection improves lymph node field relapse without an overall survival (OS) benefit. However, this trial was neither designed nor powered to detect an OS difference. In the present study, we analyzed patients in the National Cancer Database (NCDB) with stage III melanoma with pathologically involved nodes and compared survival outcomes of adjuvant radiation and no-radiation cohorts. Inclusion criteria were as follows: age at least 18 years; diagnosed 2003–2011; surgery to regional lymph nodes; pathologically involved lymph nodes; and American Joint Committee on Cancer stage (IIIA–C). We used propensity score matching analysis to compare the OS of patients with similar baseline demographic, clinical, and pathologic characteristics who received adjuvant radiation and no adjuvant radiation. Overall, 912 patients were analyzed with an average age at diagnosis of 54.4 years and a median follow-up time of 5.5 years. In this cohort, the 5-year OS was 69.0, 51.1, and 30.6% for stage IIIA, IIIB, and IIIC, respectively. On propensity score-adjusted multivariate analysis, we found that adjuvant radiation had no statistically significant impact on OS (hazard ratio: 1.09, 95% confidence interval: 0.75–1.58, P=0.640). Furthermore, age older than 60 years, number of nodes, increasing pathologic stage, and absence of immunotherapy correlated with worse OS. In this NCDB analysis, we found that the adjuvant radiotherapy for node-positive, stage III melanoma patients did not improve OS. This is consistent with TROG 02.01; however, there may be patient selection bias not accounted for by the NCDB.

Validation of cutaneous lymphoma international prognostic index (CLIPI) for mycosis fungoides and Sézary syndrome

Abstract We sought to evaluate the performance of the cutaneous lymphoma international prognostic index (CLIPI), a prognostic index for mycosis fungoides (MF), and Sézary syndrome (SS), in our cohort of patients seen at Emory University between 1998 and 2013. Additionally, we examined the prognostic significance of lactate dehydrogenase (LDH), B0a/b, and CD30 status. A total of 390 patients were included in analysis: 78.2% early stage (IA-IIA), 7.2% with SS, 53.1% male, mean age 53.5 years. CLIPI stratified patients into low, intermediate, and high-risk groups for overall survival (OS) and progression free survival (PFS) for early stage patients (p < 0.0001), but was not significant for late stage patients. On multivariable analysis for early stage patients, age >60, plaques, folliculotropic disease was significant for OS and age >60, plaques, N1/Nx was significant for PFS. In the overall cohort, CD30+, elevated LDH, and B0b were significant for worse OS and PFS.

Whole lung irradiation in stage IV Wilms tumor patients: Thyroid dosimetry and outcomes

To report the thyroid dosimetry and long‐term follow‐up of childhood cancer survivors treated with whole lung irradiation (WLI) for Wilms tumor.

First case of Merkel cell carcinoma in a young patient with Sweet syndrome

Merkel cell carcinoma (MCC) is a rare cutaneous malignancy with a high propensity for regional lymph node metastasis and recurrence. Acute febrile neutrophilic dermatosis (Sweet syndrome) is an acute inflammatory skin eruption that is commonly associated with hematologic malignancies, but cases in association with solid tumors have also been reported. We present the first case of a 49-year-old female who experienced an acute flare up of Sweet syndrome during her initial diagnosis and subsequent treatment for MCC.