This study tested the hypotheses that (1) parafunctional clenching increases pain and can lead to a diagnosis of temporomandibular disorder (TMD) pain and (2) electromyographic (EMG) activity during parafunctional clenching is significantly and positively correlated with reports of pain. Fourteen individuals without TMD participated in 5 consecutive days of 20-min long EMG biofeedback training sessions of the left and right temporalis and masseter muscles. Subjects were randomly assigned to either a Decrease or Increase group and were instructed to maintain EMG activity below 2 microV or above 10 microV during training, respectively. Two Increase subjects and no Decrease subjects were diagnosed, by a blinded examiner, with TMD pain following training. Self-reported pain posttraining was significantly higher for the Increase group. Masseter EMG activity was strongly correlated with pain. Parafunctional clenching increases pain and can lead to a diagnosis of TMD in otherwise pain-free individuals. Pain reports are positively correlated with the activity of the masseter muscle.
Gliomas are a heterogeneous group of neoplasms that comprise the majority of tumors originating in the central nervous system (CNS). In adults, the most frequently encountered of these are high-grade or malignant neoplasms of astrocytic and oligodendrocytic lineage, ie, anaplastic astrocytoma (AA), glioblastoma multiforme (GBM), and anaplastic oligodendroglioma (AO), respectively. Tumors of mixed lineage are also seen, the most common of which is designated anaplastic oligoastrocytoma (AOA). Standard treatment for these tumors is typically surgery, followed by radiation then chemotherapy. Surgery is required for a definitive histopathologic diagnosis, which in turn will dictate subsequent therapy options. Moreover, aggressive tumor resection improves survival outcomes, and in many cases, the patient's neurologic function. We generally advocate the safest, maximal resection attainable for patients with these tumors as a way to improve prognosis. In almost all cases, surgery is followed by radiation therapy. Postsurgical irradiation is the most effective treatment currently available for improving survival. There is also mounting evidence to suggest that additional radiation, given in the form of brachytherapy or radiosurgery, at initial diagnosis as a "boost" to standard radiation or at tumor recurrence, may provide added improvement in survival outcome. Radiosurgery and brachytherapy are therapies often used to treat eligible patients at this institution. Adjuvant chemotherapy, conventionally given after radiation, may offer a modest survival benefit in some patients with GBM. Bischloroethylnitrosourea (BCNU) is the typical first-line agent used, but chemotherapy seems to be most beneficial in young patients, with little if any impact on survival for patients over 60 years old. At this institution, we often defer treatment with adjuvant chemotherapy for elderly patients with GBM due to lack of efficacy and the attendant risk with chemotherapy. For anaplastic astrocytomas, oligodendrogliomas, and oligoastrocytomas, a commonly accepted standard is adjuvant chemotherapy following irradiation with the three-drug regimen--procarbazine, CCNU, and vincristine (PCV). This is due to an earlier clinical trial that showed a survival advantage in patients treated with adjuvant PCV compared with patients that received BCNU. However, recent data suggest that treatment with either PCV or BCNU may be appropriate. Both regimens now appear to have equal efficacy for anaplastic gliomas in light of a more recent analysis done with larger numbers of patients. AOs are a unique case with respect to tumor chemosensitivity and patient survival. Molecular studies have identified a subpopulation of patients with AO whose tumors have lost chromosomes 1p and 19q. Patients with this molecular pattern have an exceptional responsiveness to PCV chemotherapy and have prolonged survival. Currently, trials are being conducted to confirm this finding and to determine the best treatment regimen for these patients, with particular regard to the timing...
Background Ofranergene obadenovec (VB-111) is an anticancer viral therapy that demonstrated in a phase II study a survival benefit for patients with recurrent glioblastoma (rGBM) who were primed with VB-111 monotherapy that was continued after progression with concomitant bevacizumab. Methods This pivotal phase III randomized, controlled trial compared the efficacy and safety of upfront combination of VB-111 and bevacizumab versus bevacizumab monotherapy. Patients were randomized 1:1 to receive VB-111 1013 viral particles every 8 weeks in combination with bevacizumab 10 mg/kg every 2 weeks (combination arm) or bevacizumab monotherapy (control arm). The primary endpoint was overall survival (OS), and secondary endpoints were objective response rate (ORR) by Response Assessment in Neuro-Oncology (RANO) criteria and progression-free survival (PFS). Results Enrolled were 256 patients at 57 sites. Median exposure to VB-111 was 4 months. The study did not meet its primary or secondary goals. Median OS was 6.8 versus 7.9 months in the combination versus control arm (hazard ratio, 1.20; 95% CI: 0.91–1.59; P = 0.19) and ORR was 27.3% versus 21.9% (P = 0.26). A higher rate of grades 3–5 adverse events was reported in the combination arm (67% vs 40%), mainly attributed to a higher rate of CNS and flu-like/fever events. Trends for improved survival with combination treatment were seen in the subgroup of patients with smaller tumors and in patients who had a posttreatment febrile reaction. Conclusions In this study, upfront concomitant administration of VB-111 and bevacizumab failed to improve outcomes in rGBM. Change of treatment regimen, with the lack of VB-111 monotherapy priming, may explain the differences from the favorable phase II results. Clinical trials registration NCT02511405
Abstract. The Surveillance, Epidemiology and End Results (SEER) database was used to determine the treatment patterns, outcomes and cost of therapy in elderly patients with glioblastoma multiforme (GBM). The SEER-Medicare linked database was used to identify patients aged >66 years with GBM diagnosed between 1997 and 2009. The patients were stratified by initial treatment following diagnostic surgery (resection or biopsy) into 6 groups as follows: No treatment, standard radiation therapy (SRT) with and without concurrent temozolomide (TMZ), hypofractionated RT (HRT) with and without concurrent TMZ, or TMZ alone. The 3,759 patients identified had a median age of 74 years (range, 66-97 years). A total of ~48% of the patients received SRT without TMZ; ~10% received SRT with concurrent TMZ; ~29% received no treatment; ~10% received HRT without TMZ; ~1% received HRT with TMZ; and <1% received TMZ alone. Untreated patients had a median survival of 2 months (range, 0-89 months). Patients treated with SRT with and without concurrent TMZ had a median survival of 11 and 9 months, respectively (P=0.01). Patients treated with HRT with and without TMZ or TMZ alone had a median survivals of 3 months [adjusted hazard ratio (AHR)=0.48; 95% confidence interval (CI): 0.36-0.66], 4 months (AHR=0.55; 95% CI: 0.49-0.62) and 6 months (AHR=0.43; 95% CI: 0.29-0.62), respectively. The median post-surgery total treatment cost for patients receiving HRT with and without TMZ or TMZ alone was 63,915, 42,834 and 48,298 USD, respectively. Standard RT with concurrent TMZ was associated with improved survival, even in patients aged >75 years. HRT with and without concurrent TMZ and TMZ alone improved survival compared to the no treatment group. Therefore, in certain cases, HRT or TMZ alone may be more cost-effective, with similar survival outcomes. The various treatment options highlight the need for geriatric assessment tools to aid in therapeutic decision making.
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