Lung cancer treatment outcomes in recipients of lung transplant

BACKGROUND: Lung transplant recipients develop lung cancer more commonly than the general population. The best treatment approach for these patients is unclear. The goal of this study is to evaluate treatment outcomes in this population. METHODS: We used the Cleveland Clinic lung transplant database to identify patients diagnosed with lung cancer at the time of or after lung transplant. Transplant and lung cancer-related data were retrospectively reviewed. RESULTS: Among 847 patients underwent lung transplant between 2005 and 2013, 17 (2%) were diagnosed with lung cancer and included. Median age was 61 (range, 48–70) years. Majority were stage I/II (n=11), one had stage IIIA, five had stage IV. Non-small cell lung cancer (NSCLC) were more common than small cell lung cancer (SCLC) (n=15 vs. 2). Curative treatment was performed as lobectomy in native lung (n=1), and radiation in transplanted lung (n=2). Chemotherapy was given in 10 patients, primarily carboplatin-based doublets with docetaxel, pemetrexed, or etoposide. Six of these received palliative chemotherapy for either metastases at diagnosis (n=3) or recurrence after early stage disease (n=3). Except for one patient with complete response, all others had progressive disease following palliative chemotherapy. Overall, patients who received chemotherapy had a median survival of 7.5 months from the initiation of chemotherapy, but 30% developed grade 5 sepsis. Median survival for stage I–IIIA and stage IV were 23.2 and 2.5 months respectively. CONCLUSIONS: Lung cancer in lung transplant recipients carries various clinical courses. Patients with metastatic disease have substantial toxicities from chemotherapy and poor survival. Early stage patients should be offered treatment with modified dosages to decrease the risk of severe toxicities

Aberrant Signaling Pathways in Squamous Cell Lung Carcinoma

Lung cancer is the second most commonly occurring non-cutaneous cancer in the United States with the highest mortality rate among both men and women. In this study, we utilized three lung cancer microarray datasets generated by previous researchers to identify differentially expressed genes, altered signaling pathways, and assess the involvement of Hedgehog (Hh) pathway. The three datasets contain the expression levels of tens of thousands genes in normal lung tissues and squamous cell lung carcinoma. The datasets were combined and analyzed. The dysregulated genes and altered signaling pathways were identified using statistical methods. We then performed Fisher’s exact test on the significance of the association of Hh pathway downstream genes and squamous cell lung carcinoma

Phase 1 doseâ finding study of metformin in combination with concurrent cisplatin and radiotherapy in patients with locally advanced head and neck squamous cell cancer

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153201/1/cncr32539.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153201/2/cncr32539_am.pd

Chemotherapy in newly diagnosed primary central nervous system lymphoma

Primary central nervous system lymphoma (PCNSL) accounts for only 3% of brain tumors. It can involve the brain parenchyma, leptomeninges, eyes and the spinal cord. Unlike systemic lymphoma, durable remissions remain uncommon. Although phase III trials in this rare disease are difficult to perform, many phase II trials have attempted to define standards of care. Treatment modalities for patients with newly diagnosed PCNSL include radiation and/or chemotherapy. While the role of radiation therapy for initial management of PCNSL is controversial, clinical trials will attempt to improve the therapeutic index of this modality. Routes of chemotherapy administration include intravenous, intraocular, intraventricular or intra-arterial. Multiple trials have outlined different methotrexate-based chemotherapy regimens and have used local techniques to improve drug delivery. A major challenge in the management of patients with PCNSL remains the delivery of aggressive treatment with preservation of neurocognitive function. Because PCNSL is rare, it is important to perform multicenter clinical trials and to incorporate detailed measurements of long-term toxicities. In this review we focus on different chemotherapeutic approaches for immunocompetent patients with newly diagnosed PCNSL and discuss the role of local drug delivery in addition to systemic therapy. We also address the neurocognitive toxicity of treatment

Decreased plasma DEK Oncogene Levels Correlate with p16-Negative Disease and Advanced Tumor Stage in a Case–Control Study of Patients with Head and Neck Squamous Cell Carcinoma

Head and neck cancer (HNC) remains the sixth most common malignancy worldwide and survival upon recurrence and/or metastasis remains poor. HNSCC has traditionally been associated with alcohol and nicotine use, but more recently the Human Papilloma Virus (HPV) has emerged as a favorable prognostic risk factor for oropharyngeal HNSCC. However, further stratification with additional biomarkers to predict patient outcome continues to be essential. One candidate biomarker is the DEK oncogenic protein, which was previously detected in the urine of patients with bladder cancer and is known to be secreted by immune cells such as macrophages. Here, we investigated if DEK could be detected in human plasma and if DEK levels correlated with clinical and pathological variables of HNSCC. Plasma was separated from the peripheral blood of newly diagnosed, untreated HNSCC patients or age-matched normal healthy controls and analyzed for DEK protein using ELISA. Plasma concentrations of DEK protein were lower in p16-negative tumors compared to both normal controls and patients with p16-positive tumors. Patients with lower plasma concentrations of DEK were also more likely to have late stage tumors and a lower white blood cell count. Contrary to previously published work demonstrating a poor prognosis with high intratumoral DEK levels, we show for the first time that decreased concentrations of DEK in patient plasma correlates with poor prognostic factors, including HPV-negative status as determined by negative p16 expression and advanced tumor stage