Frontiers in oncology
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Frontiers in oncology · Jan 2015
Frequency, clinical correlates, and ratings of behavioral changes in primary brain tumor patients: a preliminary investigation.
Few studies have addressed the specific behavioral changes associated with primary brain tumor (PBT). This paper will report on the frequency and demographic/clinical correlates of such behaviors, and the reliability of rating such behaviors among people with PBT, family informants, and clinicians. The association of behavioral changes and patient functional status will also be discussed. ⋯ Behavioral changes were a common sequela of both benign and malignant PBT. Larger scale studies are required to confirm these results. The results suggest the importance of including behavior in brain cancer psychosocial assessments and the need to develop interventions to treat these patients and reduce the burden of care on families.
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Frontiers in oncology · Jan 2014
ReviewWill the Requirement by the US FDA to Simultaneously Co-Develop Companion Diagnostics (CDx) Delay the Approval of Receptor Tyrosine Kinase Inhibitors for RTK-Rearranged (ROS1-, RET-, AXL-, PDGFR-α-, NTRK1-) Non-Small Cell Lung Cancer Globally?
The discovery of anaplastic lymphoma kinase (ALK) rearrangement in non-small cell lung cancer (NSCLC) in 2007 and the approval of crizotinib for the treatment of advanced ALK-rearranged NSCLC in 2011 represents a landmark in the development of targeted oncology therapy. The approval of crizotinib was accompanied simultaneously by the approval of the Vysis (Abbott Molecular) break-apart fluorescence in situ hybridization (FISH) test as the companion diagnostic (CDx) test to detect ALK rearrangement. Pfizer, the manufacturer of crizotinib, sponsored the screening of thousands of patients and the standardization of the ALK FISH test as part of the approval process for crizotinib, a first in class ALK inhibitor. ⋯ It does not make sense for any one pharmaceutical company to shoulder the full cost of developing a particular CDx for RET-rearranged NSCLC where, once approved, it may be used by other pharmaceutical companies to gain addition labeling approval for their own RET inhibitors. Thus, the requirement by the US FDA that a specific CDx have to be co-developed and standardized for each of the molecular subtype of NSCLC as part of the drug approval process, while prudent, may have the un-intended consequence of deterring clinical development of these TKIs in these very rare molecular subsets of NSCLC. While we all march to the drumbeat of precision cancer medicine, the stringent requirement of co-development CDx for each molecular subtype of solid tumor may inadvertently make this goal substantially more difficult to achieve.
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Frontiers in oncology · Jan 2014
ReviewCompanion diagnostics for targeted cancer drugs - clinical and regulatory aspects.
Companion diagnostics (CDx) holds the promise of improving the predictability of the oncology drug development process and become an important tool for the oncologist in relation to the choice of treatment for the individual patient. A number of drug-diagnostic co-development programs have already been completed successfully, and in the clinic, the use of several targeted cancer drugs is now guided by a CDx. ⋯ In order to secure that the CDx assays have a high degree of analytical and clinical validity, they must undergo an extensive non-clinical and clinical testing before release for routine patient management. This review will give a brief introduction to some of the scientific and medical challenges related to the CDx development with specific emphasis on the regulatory requirements in different regions of the world.
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Frontiers in oncology · Jan 2014
ReviewInfections Caused by Mycobacterium tuberculosis in Recipients of Hematopoietic Stem Cell Transplantation.
Mycobacterium tuberculosis (M. tuberculosis) infections are uncommon in recipients of hematopoietic stem cell transplantation. These infections are 10-40 times commoner in recipients of stem cell transplantation than in the general population but they are 10 times less in stem cell transplantation recipients compared to solid organ transplant recipients. The incidence of M. tuberculosis infections in recipients of allogeneic stem cell transplantation ranges between <1 and 16% and varies considerably according to the type of transplant and the geographical location. ⋯ In recipients of hematopoietic stem cell transplantation, isoniazid prophylaxis has specific indications and bacillus Calmette-Guerin vaccination is contraindicated as it may lead to disseminated infection. The finding that M. tuberculosis may maintain long-term intracellular viability in human bone marrow-derived mesenchymal stem cells complicates the development of effective vaccines and strategies to eliminate tuberculosis. However, the introduction of linezolid, cellular immunotherapy, and immunomodulation in addition to autologous mesenchymal stem cell transplantation will ultimately have a positive impact on the overall management of infections caused by M. tuberculosis.