The Annual Meeting and Education Day of the Society for Neuro-Oncology (SNO) continues to grow. Each of the last few years, SNO has reported new records for conference registration, attendees, and the number of presentations submitted for consideration. The 23rd annual SNO meeting in New Orleans, LA from Thursday, November 15 through Sunday, November 18 this year was no exception.
This year’s event was notable for just how involved patients and patient advocates were relative to previous years. We detailed some of our own involvement in this year’s meeting in a press release the week of the conference, but as our Chief Scientific Officer recently mentioned in a Q&A, it was quite remarkable to see first-hand how integrated NBTS was with the program. Speaking from experience, it truly was special to see NBTS’ involvement move from purely passive during this scribe’s first SNO conference in 2014, to watching my colleagues onstage delivering presentations and participating in panel discussions (not to mention winning awards!)
Beyond this observation, here are some of the key takeaways, themes, and new insights emerging from the 2018 SNO meeting.
Clinical Trial Enrollment/Accrual
The issue of enrolling patients into clinical trials has been known and discussed in the brain tumor field – and, indeed, the entire cancer research field – for a number of years now (more on the issue, here). It’s what led NBTS to conduct our patient and caregiver survey on clinical trial participation in 2016 and subsequently launch our NBTS Clinical Trial Finder in 2017 and Brain Tumor Experience resources in 2018. But at this year’s conference, the topic permeated through multiple sessions, presentations, and panels like never before.
On Thursday, NBTS CEO David Arons and Liz Salmi, a member of the NBTS Board of Directors and a brain tumor patient, participated in a session and subsequent panel discussion titled “Improving Patient Participation in Clinical Trials.” This was followed by a similar special session Friday evening entitled, “Factors Impacting Clinical Trial Accrual.” During this session, David Arons and NBTS Research Programs Manager Amanda Bates presented results from the aforementioned NBTS survey, and David also co-presented on the topic of “patient and community factors” related to clinical trial accrual with Dr. John de Groot of MD Anderson Cancer Center.
The topic was broached across numerous other venues throughout the conference, including during the annual SNO Presidential Address by Dr. Patrick Wen of Dana-Farber Cancer Center.
Clinical Trial Design & Execution
In addition to increasing patient participation in clinical research, the topic of making clinical trials more effective and efficient was also a much-discussed topic throughout the conference. In fact, the entirety of the Education Day program on Thursday was titled, “Transforming Clinical Trials in the Modern Day Era.”
One specific solution that was discussed as a “game-changer” is the GBM AGILE adaptive clinical trial. By using an innovative trial design that tests multiple therapies across several patient groups simultaneously and adapts as data comes in, the field could more rapidly identify treatments that are working and in which patient groups (based on the molecular characteristics of their tumors).
Other potential reforms discussed included: testing investigational new drugs in a preoperative (or “neoadjuvant”) setting, relying less on single-arm phase II clinical trials as the basis for moving a treatment into larger phase III registration trials, and increasing the focus of measuring drug concentrations at the tumor site in early-phase trials.
Finally, Dr. Linda Liau of UCLA, in discussing her 20 years of experience leading studies of the immunotherapy called DCVax, expressed the need for more careful development and selection of trials endpoints. She noted that endpoints relevant for immunotherapy trials may be different from those for other treatments, and that, in general, relevant surrogate biomarkers of progression-free survival and response are desperately needed in the field to expedite trials.
Continued Focus on Patients, Care Partners, and Advocates
As noted above, a number of presentations this year featured NBTS, patients (like Liz Salmi), and other patient advocates (like David Jenkinson of The Brain Tumour Charity, Frederick Sontag of the Sontag Foundation, and Kay Verble of IBTA). The number of sessions focusing on practical and applied neuro-oncology also seem to continue to grow, as do the discussions of palliative care, patient-reported outcomes, and clinical outcome assessments. This year also saw a noticeable emphasis particularly on emotional distress in patients AND caregivers – with at least three significant talks focusing solely on caring for caregivers – as well as discussions of long-term care for survivors.
One such session was a presentation on the NBTS-funded International Low-Grade Glioma Registry, which aims, in part, to a better understand the symptoms of the disease as well as the effects from various treatments. Pilot data on patient-reported quality of life measures from 112 patients (of the 234 enrolled in the registry so far) showed that the 52 patients who had received radiation treatment (RT) at diagnosis reported significantly worse physical functioning than those patients who hadn’t received RT. But, interestingly, the patients who did not receive RT reported worse emotional and mental health scores. The ability to interpret this information is limited at this time due to the small sample size, and more analysis is needed as the registry grows.
Another study showed that symptoms of depression and anxiety occurred in 20% of long-term brain tumor survivors and that further studies are needed to identify patients most at risk for developing these symptoms so that they can be mitigated.
Continued Focus on Tumor Heterogeneity, Evolution, and Resistance Mechanisms
Understanding the tricks brain tumors play to diversify themselves, grow, adapt, and evolve could provide new insights into unique vulnerabilities to target with the right treatments for the right patients. At SNO 2018, presentations and entire sessions dedicated to topics including tumor microenvironment, epigenetics, tumor metabolism, tumor evolution, and natural history sought to reveal some of the complex mechanisms these tumors rely on to grow over time and respond in the face of treatment.
A few studies this year dove particularly into how “sex difference” might impact patients’’ response to treatment. Researchers from Washington University School of Medicine demonstrated that male GBM cells are more addicted to glutamine than female GBM cells as well as other sex difference in a main metabolic signaling pathway called “PI3K/mTOR,” suggesting that treatment strategies targeting tumor metabolism may be more effective for male patients than female patients.
Also at SNO this year, the NBTS-funded GLASS Consortium made its first data release to consortium members: unprecedented molecular characterizations of 243 tumors samples at multiple time points in their evolution from diagnosis and on through treatment to recurrence. This information will be critical in helping answer questions about tumor growth, evolution, and response to treatment. And, already from analysis of these first sets of samples, the group has noted significant differences in tumors between their molecular characteristics at diagnosis and then at recurrence.
Continued Focus of Leveraging New Technology in Neuro-Oncology
Continuing a trend spotted first emerging at the 2017 conference, there were a lot of great presentations this year about how cutting-edge tools, technology, and techniques, such as: new imaging approaches, the use of smartphones and tablets, artificial intelligence (AI), “deep learning”/“machine learning,” and computational/mathematical biology can be applied in neuro-oncology research and treatment. These tools are being leveraged for many things including making less invasive diagnoses, measuring tumor volume, studying how tumors are growing, if they are shrinking in response to therapy, deciphering the type and diversity (heterogeneity) of cells making up a tumor, and improving symptom and function management.
In one study, researchers from the University of Michigan developed and validated an AI approach to predict diagnosis immediately from tumor tissue removed during surgery. This method could help smaller hospitals – which often provide initial care to brain tumor patients, but have limited neuropathology resources – augment traditional, time- and labor-intensive manual pathology work.
In another, University of Pennsylvania researchers developed an advanced MRI approach, combined with machine learning, to reveal subtle, but critical features that would allow doctors to determine whether or not a glioma patient’s tumor has an IDH1 mutation. This is important because IDH1 is an important marker to differentiate patients with more aggressive high-grade gliomas (tumors without the IDH1 mutation). Thus, knowing IDH1 status even before a potential surgery is performed can influence treatment planning, including inclusion in clinical trials.
Clinical Trials of Note
Many updates from ongoing clinical trials were presented at SNO this year. Most were still in early stages and more data is needed. Below are a few of some of the more notable trials results presented.
- NRG Oncology, a member of the National Cancer Institute’s National Clinical Trial Network, reported resulted from a phase III clinical trial (NRG Oncology CC001) demonstrating that avoiding the hippocampus during whole-brain radiotherapy preserves cognitive function and improves patient-reported symptoms – while achieving similar survival and tumor control – in adult patients with brain metastases. NRG concluded that this approach should now become the standard of care for brain metastases patients eligible to receive whole-brain radiation and whose survival is expected to be four months or longer. In the future, researchers want to examine the implication of these findings for primary brain tumor patients.
- The European Organization for Research and Treatment of Cancer (EORTC) provided an interim analysis from a randomized, phase II clinical trials called “Intellance 2.” The trial is evaluating glioblastoma patients with increased copies of a gene called EGFR, who’ve experienced a first recurrence after initial treatment with chemotherapy and radiation, receiving an investigational drug called Depatux-M (Depatuxizumab mafofotin, ABT-806) with chemotherapy versus similar patients receiving only chemotherapy. Two years into this trial, the patients receiving Depatux-M and chemotherapy have shown improved survival over the patients receiving chemotherapy only, with 40% of the patients receiving Depatux-M alive after one year, compared to 28% of those receiving only chemotherapy. These results will need to be confirmed from the complete Intellance 2 trial when it completes, and possibly from a larger phase III trial.
- Researchers from the Collaborative Ependymoma Research Network (CERN) presented final results from a phase II clinical trial (CERN 08-02) of adult patients with recurrent ependymoma receiving temozolomide and the targeted cancer drug lapatinib. The combination was well-tolerated; improved patient symptoms, including improved quality of life with less pain; and demonstrated the ability to delay the time to further tumor progression. Because ependymoma is a rare tumor – and is even less common in adults – this was the first prospective clinical trial for adults with recurrent ependymoma and first-time chemotherapy was shown to benefit these patients. The CERN researchers concluded that this treatment strategy should be considered as a standard therapy regimen for adult ependymoma patients who’ve experienced a recurrence.
There were also a number of early clinical trial results in pediatric patients presented, including encouraging pilot trials showing the potential feasibility of using different types of immunotherapy and tumor-treating fields like Optune for pediatric brain tumor patients. Additionally, compelling preclinical research presented in pediatric high-grade gliomas pointed toward potential future trials using drugs known as PARP inhibitors in combination with radiation, as well as a medicine known as Corin.
Many more great presentations and talks were provided during the topic on a great number of subjects that impact brain tumor research, treatment, patients, and caregivers. To view all of the abstracts from the 2018 SNO Annual Meeting, visit here.