Glioblastoma in the 21st century: Wealthier patients living longer than poorer patients

ScienceDaily (June 2, 2011) — Survival rates of wealthier patients and those younger than 70 with glioblastoma, the most common and aggressive malignant brain tumor, have improved since 2000, whereas rates for those living in poorer areas and older than 70 have remained stagnant, according to an abstract being presented at the American Society of … Continue reading “Glioblastoma in the 21st century: Wealthier patients living longer than poorer patients”

ScienceDaily (June 2, 2011) — Survival rates of wealthier patients and those younger than 70 with glioblastoma, the most common and aggressive malignant brain tumor, have improved since 2000, whereas rates for those living in poorer areas and older than 70 have remained stagnant, according to an abstract being presented at the American Society of Clinical Oncology annual meeting in Chicago by Thomas Jefferson University Hospital researchers.

The addition of concurrent and adjuvant temozolomide, a chemotherapy drug also referred to as TMZ, to post-operative radiation therapy has been shown to improve overall survival in randomized trials for patients younger than 70, but it was unknown if this benefit translated down to the population-based level.

To answer this, researchers performed a population-based survival analysis of newly diagnosed glioblastoma patients (from 2000 to 2007) covering the period before and after the introduction of temozolomide. They further analyzed the impact of mean regional income on any improvements in overall survival during this time period.

Survival statistics and pertinent clinical and demographic variables were extracted from the Survival, Epidemiology and End Results (SEER) Database for patients diagnosed. Patients were divided into income quartiles based on mean household income in their county of residence.

From 2001 to 2007, the median survival time increased from 7 to 9 months for the entire population. One-year survival rate increased from 29 percent to 39 percent.

Outcomes in patients older than 70 years did not improve over this period, even amongst patients who had gross total resection and radiation therapy. Over the study period, the absolute disparity in one-year survival between economically poor-and-affluent areas increased from 6.6 percent to 10.1 percent.

“The management of patients with glioblastoma continues to be a challenge for treating oncologists,” said Mark Mishra, M.D., of the department of radiation oncology at Thomas Jefferson University Hospital. “The results of this large, population-based analysis indicate that recent advances in the treatment of glioblastoma patients have resulted in a small, but significant improvement in overall survival over the past decade.

“However, these improvements have also been accompanied with a widening of the health disparities gap for these patients.”

Future efforts should be made to identify and mitigate factors contributing to the widening economic disparities gap, according to the researchers.

There are approximately 17,000 primary brain tumors diagnosed in the United States each year, 60 percent of which are gliomas. The most common and malignant glioma is glioblastoma, the type of brain cancer Senator Ted Kennedy was diagnosed with and died from.

Other authors include Adam Dicker, M.D., Ph.D., Chair of Radiation Oncology at Thomas Jefferson University Hospital, Maria Werner-Wasik, M.D., David W. Andrews, M.D., Xinglei Shen, M.D., Timothy Showalter, M.D., John Glass, M.D., all from Thomas Jefferson University, and Zvi Symon, of Sheba Medical Center in Israel, and Yaacov R. Lawrence, M.D., a resident in radiation oncology at Jefferson and director of the Center for Translational Research in Radiation Oncology, Sheba Medical Center in Israel.


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The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Thomas Jefferson University, via EurekAlert!, a service of AAAS.


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Emerging trends in radiation therapy for women over 70 with early stage breast cancer

ScienceDaily (June 2, 2011) — Patterns of radiation usage in breast conserving therapy for women 70 years and older with stage I breast cancer are changing: more women are opting for radioactive implants and those with estrogen positive tumors are opting out of radiation therapy, according to an abstract being presented at the American Society of Clinical Oncology annual meeting in Chicago by Thomas Jefferson University Hospital researchers.

In another abstract, the researchers report that women with estrogen negative tumors were 91 percent more likely to die from breast cancer if they did not receive radiation therapy after a lumpectomy.

Given the relatively recent developments in radiation therapy (i.e., an increased use of brachytherapy and external beams) and data supporting the idea that radiation isn’t necessary for women with estrogen positive tumors, researchers wanted to see how actual practice patterns were impacted.

Researchers found that there was a modest increase in the percentage of women with estrogen receptor positive cancers who did not get radiation therapy starting around 2004, and increasing use of radioactive implants, such the MammoSite, Contura, Savi or similar devices, since 2002.

There was also a corresponding drop in women who received external beam radiation, according to Xinglei Shen, M.D., a resident in the Department of Radiation Oncology at Thomas Jefferson University Hospital. “Among women with estrogen receptor negative cancers, there was not the same increase in frequency of women who did not get radiation, but there was an increased use of radioactive implants,” he said.

The consequence of those findings was determining what impact omitting radiation has on survival. While there is data that the omission of radiation therapy in women with estrogen receptor positive tumors who receive endocrine therapy, such as Tamoxifen, is not associated with a survival difference, limited data exists for estrogen receptor negative tumors in older women who undergo breast conservation.

“From the randomized trial data, we know that women with estrogen receptor positive stage I breast cancer have no detriment to survival by avoiding radiation, as long as they took Tamoxifen,” Dr. Shen said. “However, it is unknown if this would be the case in women with estrogen receptor negative cancer.”

Dr. Shen worked with Jefferson Medical College student Andrzej Wojcieszynski to examine survival in these women, and found that they were 91 percent more likely to die from breast cancer if they did not receive radiation therapy after a lumpectomy. (Abstract #1037).

“We have to be cautious when interpreting survival data from the SEER because of potential confounding variables, such as the health of the patients and use of chemotherapy,” Dr. Shen said. “However, these data do raise hypotheses for future study.”

“Our conclusion is that adjuvant radiation therapy after lumpectomy reduces breast cancer mortality in women over 70 with stage I, estrogen receptor negative breast cancers, and that radiation is currently underutilized in these women,” said Wojcieszynski.


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The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Thomas Jefferson University, via EurekAlert!, a service of AAAS.


Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

New therapy for blood cancers using drug combo

ScienceDaily (June 2, 2011) — Reported in the journal Clinical Cancer Research, the study determined the maximum tolerated dose with acceptable side effects for this novel drug combination. The trial represented the first time a proteasome inhibitor such as Bortezomib was combined with a cell cycle inhibitor such as Alvocidib to treat patients with cancer. Proteasome inhibitors work by blocking the action of proteasomes, which are large protein complexes that help destroy proteins that are no longer needed by the cell. Cell cycle inhibitors disrupt the sequence of events that allow cells to undergo cell division and duplication. They also have the ability to block gene transcription.

The trial included 16 patients who had either indolent (non-aggressive) non-Hodgkin’s lymphoma, mantle cell lymphoma or multiple myeloma. After they received the treatments over a 21-day cycle, there were two complete responses, meaning that all detectable traces of the cancer were gone, and five partial responses.

“Therapeutic responses tend to be rare in Phase I trials, but 44 percent of our patient sample responded to the therapy. Interestingly, some patients who previously had no response to Bortezomib, or progressed after Bortezomib therapy, responded to the combination,” says Beata Holkova, M.D., a hematologist-oncologist at VCU Massey and co-investigator on this clinical trial. “Because of the small patient sample size, we can’t draw definitive conclusions about the effectiveness of the therapy, but we were quite encouraged by the results.”

The patients received Bortezomib intravenously on days 1, 4, 8 and 11 and Alvocidib on days 1 and 8. Bortezomib’s therapeutic dose alone was not tested because it has already been established and approved to treat certain blood cancers. However, for Alvocidib, the researchers escalated the dose until the maximum tolerated dose was identified. The same researchers are also currently completing a second Phase I clinical trial testing a different delivery schedule of Alvocidib. Although not yet completed, the initial results of this trial appear comparable to the present study.

“This is one of the first trials of its type in which two targeted agents which interfere with two very different biological processes are being combined to treat patients with blood cancers,” says co-investigator Steven Grant, M.D., associate director for translational research, co-program leader of Developmental Therapeutics and professor of internal medicine at VCU Massey.

The rationale for this study was developed in Grant’s laboratory when synergistic interactions between proteasome and cell cycle inhibitors in malignant blood cancer cells were discovered by Yun Dai, M.D., Ph.D., associate professor of internal medicine at VCU Massey. This laboratory research established the basis for a V Foundation Translational Research Award, which with additional funding from the National Institutes of Health provided the resources necessary to translate the laboratory findings into clinical trials.

Moving forward, the researchers are working with the NCI to develop a Phase II clinical trial to test the effectiveness of this drug therapy. The trial will be conducted in collaboration with multiple institutions to compare the effectiveness of fixed doses of the drug combination in a larger patient population.

Grant and Holkova collaborated with John Roberts, M.D., E. Brent Perkins, M.D., Viswanathan Ramakrishnan, Ph.D., Mary Beth Tombes, R.N., M.N., Ellen Shrader, R.N., Martha Wellons, R.N., Kevin Hogan, Ph.D., Sarah Kolla, M.D., and Talreja, Neha, all from VCU Massey Cancer Center and the VCU School of Medicine; G. David Roodman, M.D., Ph.D., from the University of Pittsburgh Department of Medicine; Domenico Coppola, M.D., Loveleen Kang, Jana Dawson and Daniel Sullivan, M.D., from H. Lee Moffitt Cancer Center and Research Institute; Robert K. Stuart, M.D., from the University of South Carolina Department of Medicine; and William D. Figg, Sr., Pharm.D., Austin Doyle, M.D., and John Wright, M.D., Ph.D., from the National Cancer Institute.


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The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Virginia Commonwealth University.


Journal Reference:

  1. B. Holkova, E. B. Perkins, V. Ramakrishnan, M. B. Tombes, E. Shrader, N. Talreja, M. D. Wellons, K. T. Hogan, G. D. Roodman, D. Coppola, L. Kang, J. Dawson, R. K. Stuart, C. Peer, W. D. Figg, S. Kolla, A. Doyle, J. Wright, D. M. Sullivan, J. D. Roberts, S. Grant. Phase I Trial of Bortezomib (PS-341; NSC 681239) and Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory B-Cell Neoplasms. Clinical Cancer Research, 2011; 17 (10): 3388 DOI: 10.1158/1078-0432.CCR-10-2876

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.