Understanding the patient experience and treatment benefits in patients with non-small-cell lung cancer with brain metastasis.

BACKGROUND: Despite the high prevalence of brain metastases (BM) secondary to non-small-cell lung cancer (NSCLC) (NSCLC/BM), patients' experiences (symptoms and impacts) are not fully understood. This study sought to understand the patient experience with NSCLC/BM and identify a patient-reported outcome (PRO) measure fit to capture the most important NSCLC/BM symptoms and impacts. METHODS: A targeted literature review was completed; the National Comprehensive Cancer Network (NCCN)/Functional Assessment of Cancer Therapy-Brain Symptom Index, 24-item version (NFBrSI-24) was identified as a relevant measure that assessed the core symptoms and impacts associated with NSCLC/BM. Qualitative interviews composed of concept elicitation and cognitive debriefing with oncologists (n = 3) and adult patients (n = 16) with NSCLC/BM were conducted to confirm the content validity and evaluate the relevance and appropriateness of the NFBrSI-24 for this condition. RESULTS: The NSCLC/BM symptoms and impacts identified in the literature and reported by oncologists and patients were consistent and captured in the NFBrSI-24. Study participants reported significant burden associated with the symptoms (commonly fatigue, headache) and impacts of NSCLC/BM. Participants indicated that the NFBrSI-24 captured their most salient experiences with NSCLC/BM and that symptom improvement or a delay in progression, as measured by the NFBrSI-24, would be meaningful. During the cognitive debriefing, participants generally indicated that the NFBrSI-24 was comprehensive and easy to understand/answer and that it assessed symptoms they considered most important to treat. CONCLUSIONS: These results suggest that the NFBrSI-24 adequately captures an appropriate measure of NSCLC/BM symptoms and impact.

Surveillance imaging frequency in adult patients with lower-grade (WHO Grade 2 and 3) gliomas.

With improved outcome following aggressive treatment in patients with grade 2 and 3 IDH-mutant (IDHmt), 1p/19q codeleted oligodendroglioma and IDHmt, non-codeleted astrocytoma, prolonged surveillance is desirable for early detection of tumor growth and malignant transformation. Current National Comprehensive Cancer Network (NCCN) guidelines provide imaging follow-up recommendations based on molecular classification of lower-grade gliomas, although individualized imaging guidelines based on treatments received and after tumor recurrence are not clearly specified. Other available guidelines have yet to incorporate the molecular biomarkers that inform the WHO classification of gliomas, and in some cases do not adequately consider current knowledge on IDHmt glioma growth rate and recurrence patterns. Moreover, these guidelines also do not provide specific recommendations for concerning clinical symptoms or radiographic findings warranting imaging studies out of prespecified intervals. Focusing on molecularly defined grade 2 and 3 IDHmt astrocytomas and oligodendrogliomas, we review current knowledge of tumor growth rates and time to tumor progression for each tumor type and propose a range of recommended MRI surveillance intervals for both the newly diagnosed and recurrent tumor setting. Additionally, we summarize situations in which imaging is advisable outside of these intervals.

The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients.

Accurate pathologic diagnoses and molecularly informed treatment decisions for a wide variety of cancers depend on robust clinical molecular testing that uses genomic, epigenomic, and transcriptomic-based tools. Nowhere is this more essential than in the workup of brain tumors, as emphasized by the incorporation of molecular criteria into the 2016 World Health Organization classification of central nervous system tumors and the updated official guidelines of the National Comprehensive Cancer Network. Despite the medical necessity of molecular testing in brain tumors, access to and utilization of molecular diagnostics is still highly variable across institutions, and a lack of reimbursement for such testing remains a significant obstacle. The objectives of this review are (i) to identify barriers to adoption of molecular testing in brain tumors, (ii) to describe the current molecular tools recommended for the clinical evaluation of brain tumors, and (iii) to summarize how molecular data are interpreted to guide clinical care, so as to improve understanding and justification for their coverage in the routine workup of adult and pediatric brain tumor cases.

Phase I study of sorafenib and tipifarnib for recurrent glioblastoma: NABTC 05-02.

Recurrent glioblastoma (GBM) has a very low 6-month progression free survival (PFS) with currently available treatments. Combination chemotherapy to target multiple cell signaling pathways is currently being investigated in order to improve prognosis for recurrent disease. The purpose of this phase I study was to determine the maximum tolerated dose (MTD) for the combination of tipifarnib and sorafenib for the treatment of recurrent GBM. Patients with pathologically proven WHO grade IV GBM and radiographically proven tumor recurrence were eligible for this study. Treatments included sorafenib at twice daily and escalating dosages of tipifarnib. Dose-limiting toxicity (DLT) was determined over the first 28-days of treatments, and the MTD was determined in a 3 + 3 study design. We enrolled 24 patients, and 21 patients completed the MTD period. The study was stopped early with no MTD determination for excessive toxicities. The last dose level reached was sorafenib at 200 mg twice a day and tipifarnib 100 mg twice a day on an alternating week schedule. The DLTs included diarrhea, lipase elevation, hypophosphatemia, and arthralgia. The combination of sorafenib and tipifarnib has excessive toxicities and full single agent dosages could not be achieved in combination.

Crude drugs as anticancer agents.

Although tremendous progress has been made in basic cancer biology and in the development of novel cancer treatments, cancer remains a leading cause of death in the world. The etiopathogenesis of cancer is complex. Besides genetic predisposition, known environmental factors associated with cancer are: diet, lifestyle, and environmental toxins. Toxicity of drugs and eventual relapse of cancers contribute to high cancer death rates. Current therapeutic interventions for cancer- surgery, chemotherapy, radiotherapy, thermotherapy, etc. are far from being curative for many forms of cancer. Chemotherapy, in particular, though the most commonly used cancer treatment, is usually associated with side effects with varying degrees of severity. The purpose of this brief review is to assemble current literature on some crude drugs and to focus on their beneficial roles and drug targets in cancer therapy and chemo-prevention. Although their pharmacological mechanisms and biochemical roles in cancer biology and tumor chemo-prevention are not fully understood, crude drugs are believed to have nutriceutical effects upon cancer patients.

Novel therapies for malignant gliomas.

The impact of cytotoxic therapies on the outcome of glioblastoma has been modest thus far. Yet it is clear that subsets of high-grade gliomas exist that are sensitive to treatment. Patients deemed resistant to the current standard approach may be selected for alternative therapies, thereby avoiding treatment toxicity from an ineffective treatment. The future of novel therapies lies in our understanding of the molecular biology of gliomas and their stem cells. Not only will this drive the development of new agents, it will also lead to tailored therapies for specific tumors. Yet much research is still needed at all levels, from the identification of molecular markers to the development and application of novel therapeutics.