Search

Background We observed rapid tumor progression following COVID-19 infection among patients with glioblastoma and sought to systematically characterize their disease course in a retrospective case–control study. Methods Using an institutional database, we retrospectively identified a series of COVID-19-positive glioblastoma cases and matched them by age and sex 1:2 to glioblastoma controls who had a negative COVID-19 test during their disease course. Demographic and clinical data were analyzed. Hyperprogression was defined using modified response evaluation criteria in solid tumors criteria. Time to progression and overall survival were estimated using the Kaplan–Meier method. Results Thirty-two glioblastoma cases with positive COVID-19 testing were matched to 64 glioblastoma controls with negative testing; age, sex, and molecular profiles did not differ between groups. Progression events occurred in 27 cases (84%) and 46 controls (72%). Of these, 14 cases (52%) presented with multifocal disease or leptomeningeal disease at progression compared with 10 controls (22%; P  = .0082). Hyperprogression was identified in 13 cases (48%) but only 4 controls (9%; P  = .0001). Cases had disease progression at a median of 35 days following COVID-19 testing, compared with 164 days for controls (P  = .0001). Median survival from COVID-19 testing until death was 8.3 months for cases but 17 months for controls (P  = .0016). Median overall survival from glioblastoma diagnosis was 20.7 months for cases and 24.6 months for controls (P  = .672). Conclusions Patients with glioblastoma may have accelerated disease progression in the first 2 months after COVID-19 infection. Infected patients should be monitored vigilantly. Future investigations should explore tumor-immune microenvironment changes linking tumor progression and COVID-19. [ABSTRACT FROM AUTHOR]

Background Patients with relapsed intracranial germinoma can achieve durable remission with standard chemotherapy regimens and/or reirradiation; however, innovative therapies are required for patients with relapsed and/or refractory intracranial nongerminomatous germ cell tumors (NGGCTs) due to their poor prognosis. Improved outcomes have been reported using reinduction chemotherapy to achieve minimal residual disease, followed by marrow-ablative chemotherapy (HDCx) with autologous hematopoietic progenitor cell rescue (AuHPCR). We conducted a phase II trial evaluating the response and toxicity of a 3-drug combination developed for recurrent intracranial germ cell tumors consisting of gemcitabine, paclitaxel, and oxaliplatin (GemPOx). Methods A total of 9 patients with confirmed relapsed or refractory intracranial GCT were enrolled after signing informed consent, and received at least 2 cycles of GemPOx, of which all but 1 had relapsed or refractory NGGCTs. One patient with progressive disease was found to have pathologically confirmed malignant transformation to pure embryonal rhabdomyosarcoma (without GCT elements), hence was ineligible and not included in the analysis. Patients who experienced sufficient responses proceeded to receive HDCx with AuHPCR. Treatment response was determined based on radiographic tumor assessments and tumor markers. Results A total of 7 patients achieved sufficient response and proceeded with HDCx and AuHPCR, and 5 subsequently received additional radiotherapy. A total of 2 patients developed progressive disease while receiving GemPOx. Myelosuppression and transaminitis were the most common treatment-related adverse events. With a mean follow-up of 44 months, 4 patients (3 NGGCTs, 1 germinoma) are alive without evidence of disease. Conclusions GemPOx demonstrates efficacy in facilitating stem cell mobilization, thus facilitating the feasibility of both HDCx and radiotherapy. [ABSTRACT FROM AUTHOR]

Background: Collaborative relationships between academic oncology and industry (pharmaceutical, biotechnology, "omic," and medical device companies) are essential for therapeutic development in oncology; however, limited research on engagement in and perceptions of these relationships has been done. Methods: Survey questions were developed to evaluate relationships between academic oncology and industry. An electronic survey was delivered to 1000 randomly selected members of the American Society of Clinical Oncology, a professional organization for oncologists, eliciting respondents' views around oncology‐industry collaborations. The responses were analyzed according to prespecified plans. Results: There were 225 survey respondents. Most were from the United States (70.0%), worked at an academic institution (60.1%), worked in medical oncology (81.2%), and had an active relationship with industry (85.8%). One quarter (26.7%) of respondents reported difficulty establishing a relationship with industry collaborators, and most respondents (75%) did not report having had mentorship in developing these relationships. The majority (85.3%) of respondents considered these collaborations important to their careers. Respondents generally thought that scientific integrity was preserved (92%), and most respondents (95%) had little concern over the quality of the collaborative product. Many (60%) shared concerns over potential conflict of interest if an individual with a compensated relationship promoted an industry product for clinical care/research, yet most respondents (67%) stated these relationships did not shape their interactions with patients. Conclusions: This study provides novel data characterizing the nature of collaborative relationships between clinicians, researchers, and industry in oncology. Although respondents considered these collaborations an important part of clinical and academic oncology, formal education or mentorship around these relationships was rare. Conflicting findings around conflict of interest highlight the importance of more dedicated research in this area. Plain Language Summary: Business enterprises in health care play a central role in cancer research and care, driving the development of new medical testing, drugs, and devices. Effective working relationships among clinicians, researchers, and these industry partners can promote innovative research and enhance patient care. Study of these collaborations has been limited to date. Through distribution of a questionnaire to cancer clinicians and researchers, we found that most participants consider these relationships valuable, though they find establishing such relationships challenging partly because of gaps in educational programs in this area. Our findings also highlight the need for further policy around the potential bias these relationships can introduce. Oncology‐industry collaborations can be mutually beneficial relationships that contribute to both scientific and clinical innovation. Despite their value, a deficit of education and policy around these collaborations is recognized by cancer clinicians and researchers. [ABSTRACT FROM AUTHOR]

Simple Summary: The loss of tumor antigens prevents the immune system from recognizing and destroying cancer cells. Immune cells can remove these antigens and express them on their surface. Other immune cells becoming confused, kill the anti-tumor immune cells. By blocking this process using a drug commonly used to treat a variety of eye conditions, we were able to restore anti-tumor immune responses for impaired T cells in mouse models of brain cancer. Background: Chimeric antigen receptor (CAR) T cells have recently been demonstrated to extract and express cognate tumor antigens through trogocytosis. This process may contribute to tumor antigen escape, T cell exhaustion, and fratricide, which plays a central role in CAR dysfunction. We sought to evaluate the importance of this effect in epidermal growth factor receptor variant III (EGFRvIII) specific CAR T cells targeting glioma. Methods: EGFRvIII-specific CAR T cells were generated from various donors and analyzed for cytotoxicity, trogocytosis, and in vivo therapeutic activity against intracranial glioma. Tumor autophagy resulting from CAR T cell activity was evaluated in combination with an autophagy inducer (verteporfin) or inhibitor (bafilomycin A1). Results: CAR T cell products derived from different donors induced markedly divergent levels of trogocytosis of tumor antigen as well as PD-L1 upon engaging target tumor cells correlating with variability in efficacy in mice. Pharmacological facilitation of CAR induced-autophagy with verteporfin inhibits trogocytic expression of tumor antigen on CARs and increases CAR persistence and efficacy in mice. Conclusion: These data propose CAR-induced autophagy as a mechanism counteracting CAR-induced trogocytosis and provide a new strategy to innovate high-performance CARs through pharmacological facilitation of T cell-induced tumor death. [ABSTRACT FROM AUTHOR]

Objective: Leptomeningeal carcinomatosis (LMC), a common complication of advanced malignancies, is associated with high morbidity and mortality, yet diagnosis and treatment decisions remain challenging. This study describes the diagnostic and treatment modalities for LMC and identifies factors associated with overall survival (OS). Materials and Methods: We performed a single-institution retrospective study (registration #: OSU2016C0053) of 153 patients diagnosed with LMC treated at The Ohio State University, Comprehensive Cancer Center, (OSUCCC)-James between January 1, 2010 and December 31, 2015. Results: Median age at diagnosis was 55.7 years, and 61% had Eastern Cooperative Oncology Group baseline performance status =1. Most common primary tumors were breast (43%), lung (26%), and cutaneous melanoma (10%). At presentation, most patients were stage III-IV (71%) with higher grade tumors (grade III: 46%). Metastases to bone (36%), brain (33%), and lung (12%) were the most common sites with a median of 0.5 years (range, 0-14.9 years) between the diagnosis of first metastasis and of LMC. 153 (100%) patients had MRI evidence of LMC. Of the 67 (44%) who underwent lumbar puncture (LP), 33 (22%) had positive cerebrospinal fluid (CSF) cytology. Most patients received radiotherapy for LMC (60%) and chemotherapy (93%) for either the primary disease or LMC. 28 patients received intrathecal chemotherapy, 22 of whom had a primary diagnosis of breast cancer. 98% died with median OS of all patients was 1.9 months (95% CI: 1.3-2.5 months). Conclusion: Despite improved treatments and targeted therapies, outcomes of LMC remain extremely poor. Positive CSF cytology was associated with lower OS in patients who had cytology assessed and specifically in patients with breast cancer. CSF cytology serves as an important indicator for prognosis and helps aid in developing individualized therapeutic strategies for patients with LMC. [ABSTRACT FROM AUTHOR]

Background Radiation necrosis (RN) is a potential complication after radiation therapy for brain tumors. It is hypothesized that VEGF plays an important role in the pathophysiology of RN. Bevacizumab, a monoclonal antibody against VEGF-A, is often successful in the management of RN. The objective of this study is to assess whether VEGF receptor (VEGFR) inhibitors, a group of oral tyrosine kinase inhibitors (TKIs), can prevent or reverse RN. Methods We retrospectively studied a cohort of 102 patients with renal cell carcinoma and brain metastases seen at The Ohio State University James Cancer Center between January 1, 2011 and April 30, 2019. We identified those who developed RN and analyzed the temporal relationship between the use of VEGFR TKIs and the development of RN. Results The cumulative incidence of RN is 13.7% after radiation treatments that included LINAC-based stereotactic radiosurgery, fractionated stereotactic radiotherapy, or Gamma Knife radiosurgery. There was no statistically significant difference in the cumulative incidence of RN between patients taking TKIs and patients who were off TKIs (9.9% and 11.5% respectively, P  = .741). The median time to development of RN was only numerically shorter in patients taking TKIs (151 vs 315 days, P  = .315). One patient developed RN after stopping cabozantinib. Eight patients developed RN while on cabozantinib, pazopanib, or sunitinib. One patient was started on axitinib during active RN without significant improvement subsequently. Conclusions VEGFR TKIs do not consistently prevent RN. The therapeutic effects of VEGFR TKIs against RN warrant further research. [ABSTRACT FROM AUTHOR]

Background: Carboplatin is a potent cytoreductive agent for a variety of solid tumors. However, when delivered systemically, clinical efficacy for the treatment of high grade gliomas is poor due to limited penetration across the blood-brain barrier (BBB). Direct intracerebral (IC) convection-enhanced delivery (CED) of carboplatin has been used to bypass the BBB and successfully treat the F98 rat glioma. Based on these studies, we initiated a Phase I clinical trial. Objective: This Phase I clinical trial was conducted to establish the maximum tolerated dose and define the toxicity profile of carboplatin delivered intracerebrally via convection enhanced delivery (CED) for patients with high grade glial neoplasms. Methods: Cohorts of 3 patients with recurrent WHO grade III or IV gliomas were treated with escalating doses of CED carboplatin (1–4 μg in 54mL over 72 hours) delivered via catheters placed at the time of recurrent tumor resection. The primary outcome measure was determination of the maximum tolerated dose (MTD). Secondary outcome measures included overall survival (OS), progression-free survival (PFS), and radiographic correlation. Results: A total of 10 patients have completed treatment with infusion doses of carboplatin of 1μg, 2μg, and 4μg. The total planned volume of infusion was 54mL for each patient. All patients had previously received surgery and chemoradiation. Histology at treatment include GBM (n = 9) and anaplastic oligodendroglioma (n = 1). Median KPS was 90 (range, 70 to 100) at time of treatment. Median PFS and OS were 2.1 and 9.6 months after completion of CED, respectively. A single adverse event possibly related to treatment was noted (generalized seizure). Conclusions: IC CED of carboplatin as a potential therapy for recurrent malignant glioma is feasible and safe at doses up to 4μg in 54mL over 72 hours. Further studies are needed to determine the maximum tolerated dose and potential efficacy. [ABSTRACT FROM AUTHOR]