A randomized phase II study of everolimus in combination with chemoradiation in newly diagnosed glioblastoma: results of NRG Oncology RTOG 0913.

Background: This phase II study was designed to determine the efficacy of the mammalian target of rapamycin (mTOR) inhibitor everolimus administered daily with conventional radiation therapy and chemotherapy in patients with newly diagnosed glioblastoma. Methods: Patients were randomized to radiation therapy with concurrent and adjuvant temozolomide with or without daily everolimus (10 mg). The primary endpoint was progression-free survival (PFS) and the secondary endpoints were overall survival (OS) and treatment-related toxicities. Results: A total of 171 patients were randomized and deemed eligible for this study. Patients randomized to receive everolimus experienced a significant increase in both grade 4 toxicities, including lymphopenia and thrombocytopenia, and treatment-related deaths. There was no significant difference in PFS between patients randomized to everolimus compared with control (median PFS time: 8.2 vs 10.2 mo, respectively; P = 0.79). OS for patients randomized to receive everolimus was inferior to that for control patients (median survival time: 16.5 vs 21.2 mo, respectively; P = 0.008). A similar trend was observed in both O6-methylguanine-DNA-methyltransferase promoter hypermethylated and unmethylated tumors. Conclusion: Combining everolimus with conventional chemoradiation leads to increased treatment-related toxicities and does not improve PFS in patients with newly diagnosed glioblastoma. Although the median survival time in patients receiving everolimus was comparable to contemporary studies, it was inferior to the control in this randomized study.

"It wasn't as bad as I thought it would be": a qualitative study of early stage non-small cell lung cancer patients after treatment.

OBJECTIVE: While surgical resection is recommended for most patients with early stage lung cancer, stereotactic body radiotherapy (SBRT) is being increasingly utilized. Provider-patient communication regarding risks/benefits of each approach may be a modifiable factor leading to improved patient-centered outcomes. Our objective was to determine a framework and recommended strategies on how to best communicate with patients with early stage non-small cell lung cancer (NSCLC) in the post-treatment setting. We qualitatively evaluated the experiences of 11 patients with early clinical stage NSCLC after treatment, with a focus on treatment experience, knowledge obtained, communication, and recommendations. We used conventional content analysis and a patient-centered communication theoretical model to guide our understanding. RESULTS: Five patients received surgery and six received SBRT. Both treatments were generally well-tolerated. Few participants reported communication deficits around receiving follow-up information, although several had remaining questions about their treatment outcome (mainly those who underwent SBRT). They described feeling anxious regarding their first surveillance CT scan and clinician visit. Overall, participants remained satisfied with care because of implicit trust in their clinicians rather than explicit communication. Communication gaps remain but may be addressed by a trusting relationship with the clinician. Patients recommend clinicians give thorough explanations and personalize when possible.

"Even if I Don't Remember, I Feel Better". A Qualitative Study of Patients with Early-Stage Non-Small Cell Lung Cancer Undergoing Stereotactic Body Radiotherapy or Surgery.

RATIONALE: While surgical resection is recommended for most patients with early stage lung cancer according to the National Comprehensive Cancer Network guidelines, stereotactic body radiotherapy is increasingly being used. Provider-patient communication regarding the risks and benefits of each approach may be a modifiable factor leading to improved patient-centered outcomes. OBJECTIVES: To qualitatively describe the experiences of patients undergoing either surgery or stereotactic body radiotherapy for early stage non-small cell lung cancer. METHODS: We qualitatively evaluated and used content analysis to describe the experiences of 13 patients with early clinical stage non-small cell lung cancer before undergoing treatment in three health care systems in the Pacific Northwest, with a focus on knowledge obtained, communication, and feelings of distress. MEASUREMENTS AND MAIN RESULTS: Although most participants reported rarely having been told about other options for treatment and could not readily recall many details about specific risks of recommended treatment, they were satisfied with their care. The patients paradoxically described clinicians as displaying caring and empathy despite not explicitly addressing their concerns and worries. We found that the communication domains that underlie shared decision making occurred infrequently, but that participants were still pleased with their role in the decision-making process. We did not find substantially different themes based on where the participant received care or the treatment selected. CONCLUSIONS: Patients were satisfied with all aspects of their care, despite reporting little knowledge about risks or other treatment options, no direct elicitation of worries from providers, and a lack of shared decision making. While the development of effective communication strategies to address these gaps is warranted, their effect on patient-centered outcomes, such as distress and decisional conflict, is unclear.

A randomized phase I/II study of ABT-888 in combination with temozolomide in recurrent temozolomide resistant glioblastoma: an NRG oncology RTOG group study.

This study tested the hypothesis that ABT-888 (velparib), a poly (ADP-ribose) polymerase (PARP) inhibitor, can modulate temozolomide (TMZ) resistance in recurrent TMZ refractory glioblastoma patients. The combination regimen (TMZ/ABT-888) was tested using two randomized schedules (5 vs. 21 days), with 6-month progression free survival (PFS6) as the primary endpoint. The maximum tolerated dose (MTD) for TMZ using the 21 day of 28 TMZ schedule, in concert with 40 mg BID ABT-888 was determined in a phase I portion of this study, and previously reported to be 75 mg/m(2) (arm1). The MTD for ABT-888 (40 mg BID) and the 5 of 28 day TMZ (150-200 mg/m(2)) schedule was known from prior trials (arm2). Two cohorts were studied: bevacizumab (BEV) naïve (n = 151), and BEV refractory (n = 74). Overall ten patients were ineligible. The incidence rate of grade 3/4 myelosuppression over all was 20.0 %. For the BEV refractory cohort, the PFS 6 was 4.4 %; for the BEV naïve cohort, PFS6 was 17 %. Overall survival was similar for both arms in both the BEV naïve [median survival time (MST) 10.3 M; 95 % CI 8.4-12] and BEV refractory cohort (MST 4.7 M; 95 %CI 3.5-5.6). The median PFS was essentially the same for both arms and both cohorts at ~2.0 M (95 % CI 1.9-2.1).

Effect of radiation on segmental distraction osteogenesis in rabbits.

OBJECTIVE: To determine whether consolidation can occur during radiotherapy after segmental distraction osteogenesis. Segmental distraction osteogenesis has potential as a reconstructive option after oncologic resection of the mandible. However, postoperative radiotherapy has potentially deleterious effects on bone consolidation after distraction osteogenesis. METHODS: Tibial defects of 1.0 cm were created in 5 New Zealand white rabbits. After a 6-day latency phase, a 1.0-cm distraction segment was created in 0.3-mm increments every 12 hours. Within 24 hours of the distraction completion, the tibia received the biologic equivalent of 6000 rad (60 Gy). After 6 weeks of consolidation, the animals were humanely killed. Bone was analyzed radiographically, grossly (at autopsy), and histomorphometrically. RESULTS: Four rabbits completed the 6-week consolidation period. All specimens had evidence of calcified bone in the segmental defect on radiographic analysis. At autopsy, the volume of new bone equaled that of the removed segment. On histologic examination, the volume of new trabecular bone was similar to adjacent cortical bone. CONCLUSIONS: Consolidation of segmental distraction osteogenesis defects can occur in rabbit tibia during external beam radiotherapy. To our knowledge, this study is the first to demonstrate successful consolidation of segmental distraction osteogenesis during external beam radiotherapy.