Breaking News
March 22, 2018 - Researchers explain link between 2 key Alzheimer’s proteins
March 22, 2018 - Patients on replacement therapy with thyroid hormone may have more comorbidities
March 22, 2018 - Higher online patient ratings linked to urologists who saw fewer Medicare patients
March 22, 2018 - FDA Approves Ilumya (tildrakizumab-asmn) for the Treatment of Moderate-to-Severe Plaque Psoriasis
March 22, 2018 - Beer Raises Heart Rate; KardiaBand Hyperkalemia Test; CHD Clinics
March 22, 2018 - A retinal implant that is more effective against blindness
March 22, 2018 - New system based on artificial intelligence provides reliable detection of breast cancer
March 22, 2018 - Research offers new understanding about cause of Parkinson’s disease
March 22, 2018 - HORIBA’s Microsemi CRP analyzer improves quality of care in emergency pediatric units, study shows
March 22, 2018 - Range of Vaginal Dryness Products Can Help Postmenopausal Women: Study
March 22, 2018 - Higher Dose Tx Deemed Safe in Pulmonary TB
March 22, 2018 - Discovery of new ALS gene points to cytoskeleton as potential target for drug development
March 22, 2018 - Diet soda associated with higher odds of diabetic retinopathy
March 22, 2018 - LSD reduces ‘sense of self’
March 22, 2018 - Vitamin D deficiency linked to metabolic syndrome in postmenopausal women
March 22, 2018 - Changes in the intestines may be responsible for reversal of diabetes after bariatric surgery
March 22, 2018 - iPads and Cancer; Clot Retrieval and Stroke: It’s PodMed Double T!
March 22, 2018 - Premature births linked to changes in mother’s bacteria
March 22, 2018 - Brain SPECT scans predict treatment outcomes in patients with depression
March 21, 2018 - Researchers succeed in integrating artificial organelles into cells of living organism
March 21, 2018 - Researchers discover ‘missing mutation’ in severe infant epilepsy
March 21, 2018 - Researchers develop statistics-based computational scheme to zoom in on brain function
March 21, 2018 - Verge joins Genomics England’s Discovery Forum industry partnership
March 21, 2018 - Trovagene Announces First Patient Successfully Completes Cycle 1 of Treatment with PCM-075 in Combination with Low Dose Cytarabine (LDAC) in AML Trial
March 21, 2018 - Congenital Cardiac Cath Tx Often Strays from Guidelines
March 21, 2018 - Marked increase in cardiovascular risk factors in women after preeclampsia
March 21, 2018 - New app may help predict, track manic and depressive episodes in bipolar patients
March 21, 2018 - Discovery of genes could lead to development of novel therapies for EBV-related cancers
March 21, 2018 - High-fat, high-cholesterol diet depletes ranks of artery-protecting immune cells
March 21, 2018 - Research misconduct allegations shadow likely CDC appointee
March 21, 2018 - Most Breast Ca Patients Fail to Get Genetic Counseling
March 21, 2018 - Lopsided ear function can lead to lopsided brain development
March 21, 2018 - Acupuncture helps manage menopausal symptoms, review finds
March 21, 2018 - Motor skill training may contribute to reading skills in obese children
March 21, 2018 - Poor dental health may be related to increased diabetes risk
March 21, 2018 - Chronic opioid users at increased risk of complications after spinal fusion surgery
March 21, 2018 - Study uncovers potential therapeutic target against large family of parasites
March 21, 2018 - NSAID use linked to increased risk of atrial fibrillation
March 21, 2018 - Scientists develop brain “stethoscope” that can detect silent seizures
March 21, 2018 - New method predicts effects of global warming on disease
March 21, 2018 - Insurance Company Hurdles Burden Doctors, May Harm Patients
March 21, 2018 - Renal Transplant from HCV-Positive Donors Feasible
March 21, 2018 - Myelodysplastic syndrome: MedlinePlus Medical Encyclopedia
March 21, 2018 - Research reveals brain mechanism involved in language learning
March 21, 2018 - Many parents still hesitate to try early peanut introduction, survey finds
March 21, 2018 - Audiologist urges tinnitus sufferers facing ‘revolving door healthcare’ to seek support
March 21, 2018 - Study reveals impact of prostate cancer on wives and partners of sufferers
March 21, 2018 - ‘Almost a Miracle Drug’: What We Heard This Week
March 21, 2018 - Study shows NIH spent >$100 billion on basic science for new medicines
March 21, 2018 - Columbia researchers identify nerve cells that drive fruit fly’s escape behavior
March 21, 2018 - Sartorius Stedim Biotech selected by ABL Europe to supply single-use process technologies
March 21, 2018 - Increase in coffee consumption may help battle against colon cancer
March 21, 2018 - Hydrogel may accelerate healing of diabetic ulcers
March 21, 2018 - Dermira’s Two Phase 3 Trials Evaluating Olumacostat Glasaretil in Patients with Acne Vulgaris Did Not Meet Co-Primary Endpoints
March 21, 2018 - DePuy Synthes introduces ACTIS Total Hip System for improving initial implant stability
March 21, 2018 - ‘Oh, It Was Nothing’
March 21, 2018 - Herbal drug kratom linked to salmonella illnesses, CDC says
March 21, 2018 - New optical point-of-care device could enhance screening for thyroid nodules
March 21, 2018 - FDA Expands Approval of Adcetris (brentuximab vedotin) for First-Line Treatment of Stage III or IV Classical Hodgkin Lymphoma in Combination with Chemotherapy
March 21, 2018 - Eosinophilic Esophagitis: Late Manifestation of Allergic March
March 21, 2018 - Signaling pathway involving the Golgi apparatus identified in cells with Huntington’s disease
March 21, 2018 - Quintupling inhaled steroid doses may not benefit children with asthma
March 21, 2018 - Study shows clear connection between cardiovascular fitness in middle age and dementia risk
March 21, 2018 - Premature babies have higher risks of health complications in Bangladesh
March 21, 2018 - Child’s temperament and parenting influence weight gain in babies
March 21, 2018 - Researchers find the heart to be capable of arrhythmia termination after local gene therapy
March 21, 2018 - Inhealthcare to provide digital infrastructure for NHS to help protect people from falls
March 21, 2018 - Flu Season Finally Slowing Down
March 21, 2018 - Mixed Results for Shorter DAPT in ACS Patients
March 21, 2018 - Scientists discover fish scale-derived collagen effective for healing wounds
March 21, 2018 - Genomics England announces new partnership to improve efficiency of next-generation sequencing analysis
March 21, 2018 - Adjuvant AC chemotherapy found to be effective in treating HRD-positive breast cancer patients
March 21, 2018 - Researchers identify new treatment targets for lung diseases using big data
March 21, 2018 - Kids see more women in science than five decades ago
March 21, 2018 - Research shows link between chronic fatigue syndrome and lower thyroid hormone levels
March 21, 2018 - Alzheimer’s disease on the rise
March 21, 2018 - Two Agents Equal as Pretreatment for Adrenal Tumor Surgery
March 21, 2018 - ‘Icebreaker’ protein opens genome for T cell development, researchers find
March 21, 2018 - Women in medicine shout #Metoo about sexual harassment at work
March 21, 2018 - Mother’s pre-pregnancy waist size may be linked to child’s autism risk
Genome-wide molecular tests can guide treatment in recurrent glioblastoma, study shows

Genome-wide molecular tests can guide treatment in recurrent glioblastoma, study shows

image_pdfDownload PDFimage_print

Several patients with recurring glioblastoma, a deadly brain cancer, survived for more than a year in a clinical trial believed to be the first to use comprehensive DNA and RNA sequencing of a patient’s tumor to inform treatment for these patients in real-time. The study was led by the Translational Genomics Research Institute (TGen), UC San Francisco (UCSF) and the Ivy Foundation Early Phase Clinical Trials Consortium.

“This study demonstrates the feasibility of using genome-wide molecular tests to guide treatment in recurrent glioblastoma,” according to a scientific paper published today in Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR).

“To our knowledge, this is the first report of a prospective profiling study in recurrent glioblastoma to show patients with extended time to progression following treatment with genomics-informed therapy,” said Dr. Sara Byron, Research Assistant Professor in TGen’s Integrated Cancer Genomics Division and the study’s lead author. “This is a primary example of the benefits of genomics-driven precision medicine being applied for patients with aggressive and refractory tumors.”

Fifteen of 16 glioblastoma patients in the study conducted at UCSF received TGen’s genomics-informed treatment recommendations, in which the therapeutics suggested by a medical review panel (UCSF’s Molecular Tumor Board) were matched to each patient’s particular genetic code. Of those 15, seven patients were treated by their physicians using the genomic-based recommendations.

Key to this study was the fact that all genomic sequencing (the spelling out of the chemical DNA and RNA bases for more than 20,000 genes in the human genome), genetic analysis, and recommendations for treatment were completed in less than 35 days after surgery, ensuring that suggested therapies could begin within “a clinically acceptable time frame.”

Timely administration of therapeutics is critical

Glioblastoma is an aggressive disease, with a median overall survival of only 15 months for newly diagnosed patients. One of the major difficulties in treating glioblastoma is its intrusive penetration into adjoining tissues, which prevents the complete surgical removal of the tumors from the brain, even with follow-up radiation and chemotherapy. As a result, nearly all glioblastomas recur. Patients whose brain cancer returns are often encouraged to enter experimental clinical trials. However, even on clinical trials, further progression of the disease is seen, on average, within 4 months.

“Notably, two of the patients experienced progression-free survival — meaning their tumor did not return or increase in size — for more than a year, with one of these patients progression-free at 21 months, three times longer than the time to progression on their previous therapy,” said Dr. Michael D. Prados, the Charles B. Wilson Endowed Chair in Neurological Surgery at UCSF, and the study’s senior author.

Another major challenge in treating brain tumors is finding drugs that can penetrate the blood-brain barrier, which buffers the brain from the rest of the body’s blood-circulatory system. Located along small capillaries, the blood-brain barrier protects the brain from rapid changes in the body’s metabolic conditions and minimizes exposure to large molecules that are toxic to neurons in the brain.

The only FDA-approved standard-of-care drugs to treat glioblastoma are temozolomide, nitrosoureas, and bevacizumab.

In this study, more than 180 FDA-approved agents were reviewed, including all FDA-approved oncology drugs and a selection of repositioned agents that are approved by the FDA for other indications but show promising activity against cancer pathways. The tumor board considered the drugs supported by the genomic data for each patient, and discussed each drug’s ability to penetrate the blood-brain barrier, potential opportunities to combine treatments, drug-to-drug interactions and drug-safety profiles.

Two patients survived more than a year

One of the patients was a 58-year-old woman with recurrent glioblastoma. Genomic sequencing showed several alterations with potential therapeutic relevance. Based on mutations in her NF1 and PALB2 genes, the UCSF Molecular Tumor Board recommended treatment with a combination of trametinib, olaparib and carboplatin. “This patient continued on treatment without disease progression (for more than) 665 days after surgery,” according to the new paper, which adds, “Additional preclinical and clinical studies will be needed to determine the role of genomic context and combination therapy in the response observed for this patient.”

Another patient was a 35-year old man with recurrent glioblastoma. The study’s tumor board, focusing on the tumor’s mutations in the IDH1 and ATRX genes, recommended treatment with a combination of CCNU, carboplatin, and metformin. The patient and treating oncologist decided to pursue treatment with CCNU and metformin. “This patient remained on treatment and progression-free for just over one year,” the study said.

“This precision-medicine study provides one of the first prospective demonstrations of using genome-wide molecular profiling to guide treatment recommendations for patients with recurrent glioblastoma within a clinically actionable time frame,” said Dr. Michael Berens, TGen Deputy Director for Research Resources, and Professor and Director of TGen’s Cancer and Cell Biology Division.

“These findings provide a rationale and framework for larger prospective studies to further assess the efficacy of employing genomics-guided treatment for patients with recurrent glioblastoma,” said Dr. Berens, one of the study’s authors.


Tagged with:

About author

Related Articles