Phase IB study of gene-mediated cytotoxic immunotherapy adjuvant to up-front surgery and intensive timing radiation for malignant glioma.

PURPOSE: Despite aggressive therapies, median survival for malignant gliomas is less than 15 months. Patients with unmethylated O(6)-methylguanine-DNA methyltransferase (MGMT) fare worse, presumably because of temozolomide resistance. AdV-tk, an adenoviral vector containing the herpes simplex virus thymidine kinase gene, plus prodrug synergizes with surgery and chemoradiotherapy, kills tumor cells, has not shown MGMT dependency, and elicits an antitumor vaccine effect. PATIENTS AND METHODS: Patients with newly diagnosed malignant glioma received AdV-tk at 3 × 10(10), 1 × 10(11), or 3 × 10(11) vector particles (vp) via tumor bed injection at time of surgery followed by 14 days of valacyclovir. Radiation was initiated within 9 days after AdV-tk injection to overlap with AdV-tk activity. Temozolomide was administered after completing valacyclovir treatment. RESULTS: Accrual began December 2005 and was completed in 13 months. Thirteen patients were enrolled and 12 completed therapy, three at dose levels 1 and 2 and six at dose level 3. There were no dose-limiting or significant added toxicities. One patient withdrew before completing prodrug because of an unrelated surgical complication. Survival at 2 years was 33% and at 3 years was 25%. Patient-reported quality of life assessed with the Functional Assessment of Cancer Therapy-Brain (FACT-Br) was stable or improved after treatment. A significant CD3(+) T-cell infiltrate was found in four of four tumors analyzed after treatment. Three patients with MGMT unmethylated glioblastoma multiforme survived 6.5, 8.7, and 46.4 months. CONCLUSION: AdV-tk plus valacyclovir can be safely delivered with surgery and accelerated radiation in newly diagnosed malignant gliomas. Temozolomide did not prevent immune responses. Although not powered for efficacy, the survival and MGMT independence trends are encouraging. A phase II trial is ongoing.

E. Latunde Odeku: the first African-American neurosurgeon trained in the United States.

The advances of the Civil Rights movement in the mid-20th century and the success of the first African-American neurosurgeons trained at the Montreal Neurological Institute have led to a number of African-Americans receiving neurosurgery training within the United States. Unfortunately, the details regarding the first African-American neurosurgeon trained in the United States, E. Latunde Odeku, have largely remained in obscurity. Born on June 29, 1927 in Lagos, Nigeria, Dr. Odeku received his M.D. from the Howard University College of Medicine in 1954. He spent the next year at the University of Michigan under the tutelage of Edgar A. Kahn, chief of neurosurgery, and was impressive enough to be offered a residency position. From 1956 to 1960, he trained under Dr. Kahn at the University of Michigan. In 1961, he returned to Howard as a member of the neurosurgery faculty, during which time he became the second African-American to be certified by the American Board of Neurological Surgery. Although he received multiple job offers in the United States, he chose to return to Nigeria where he worked tirelessly, providing excellent neurosurgical care and discipleship until his death in 1974. The diligence and intelligence of E. Latunde Odeku, M.D., F.A.C.S., enabled him to become the first African-American neurosurgeon trained in the United States. A truly global pioneer, his selfless service in America and Nigeria opened the door for people from each country to enhance the field of neurosurgery.

Clarence Sumner Greene, Sr.: the first African-American neurosurgeon.

Largely because of the advances of the Civil Rights movement in the mid-20th century, an increasing number of African-Americans have had the opportunity to become physicians and enter the distinguished field of neurosurgery. Many have made the most of this opportunity, becoming prominent in both academics and private practice. Unfortunately, the details regarding the first African-American neurosurgeon, Clarence Sumner Greene, Sr., have remained in relative obscurity. Born on December 26, 1901 in Washington, D.C., Dr. Greene received his M.D. from the Howard University College of Medicine with distinction in 1936. After 7 years of general surgery residency and 4 years as a professor of surgery at Howard University, he was granted the opportunity by the legendary Wilder G. Penfield to train in neurosurgery at the world-renowned Montreal Neurological Institute from 1947 to 1949. Receiving high praise from Dr. Penfield, Dr. Greene became the first African-American certified by the American Board of Neurological Surgery on October 22, 1953. Subsequently, he was appointed as chair of neurosurgery at Howard University, where he successfully treated intracranial aneurysms, brain tumors, and herniated intervertebral discs until his tragic death in 1957. The diligence and perseverance of Clarence Sumner Greene, Sr., M.D., D.D.S., F.A.C.S. enabled him to overcome incredible odds to become the first African-American neurosurgeon, trained by Dr. Penfield at the Montreal Neurological Institute. A true pioneer, his achievements have opened the door for subsequent African-Americans to enhance the field of neurosurgery.