Mount Sinai School of Medicine researchers will present several landmark studies, including data on treatment trends in late-stage cancer, a promising multiple myeloma vaccine, and predictive models of soft tissue sarcomas, prostate and bladder cancer, at the 2012 American Society of Clinical Oncology (ASCO) meeting June 1-5, 2012 in Chicago.
Highlights of Mount Sinai research at ASCO:
Mount Sinai researchers found that 20 percent of 773,233 patients with Stage IV cancer from the National Cancer Database from 2000-2008 did not receive any anticancer treatment. Kidney and lung cancer had the highest rates of non-treatment at 25.5 and 24 percent, respectively, and prostate cancer had the lowest rate at 11.1 percent. Across all tumor types, older age, black race, lack of medical insurance, and lower income were associated with lack of treatment.
"While we were aware that some patients with advanced cancer do not receive any anticancer treatment based on our own clinical experience, we were very surprised that the proportion of patients receiving no treatment was this high," said Matthew Galsky, MD, Assistant Professor, Hematology and Medical Oncology at Mount Sinai. "Of course, there are multiple reasons for lack of treatment, many of them appropriate. However, we identified some trends to suggest that lack of access to care may play a role in many cases, a finding that warrants concern, and has implications regarding healthcare policy."
In a poster session at ASCO highlighting research works in progress, Hearn Jay Cho, MD, PhD, Assistant Professor of Hematology and Medical Oncology at Mount Sinai, and his team will describe a new multicenter study investigating a vaccine targeting multiple myeloma, a currently incurable blood cancer. Dr. Cho's team discovered that a gene called Melanoma Antigen Gene (MAGE)-A3 is highly expressed in multiple myeloma, and when that gene is "turned off," the cancer cells die and the disease cannot proliferate. Dr. Cho and his team are investigating a vaccine based on the protein produced by the MAGE-A3 gene that triggers an immune system response intended to kill multiple myeloma cells.
Paired with an adjuvant, or a chemical that boosts immune response, and white blood cells primed with the vaccine, the MAGE-A3 vaccine is administered to patients undergoing autologous stem cell transplant. The first dose is delivered six weeks before stem cell transplant; the primed white blood cells are infused three days after the stem cell transplant and boosted by a second vaccination ten days after the transplant. Over the next 270 days, the patient receives six additional booster vaccinations.
The study plans to enroll 16 patients. If a 50 percent response to the vaccination is achieved, the research team will initiate a study in a larger patient population to further evaluate clinical efficacy.
"While currently available treatments for multiple myeloma help patients live longer and with a better quality of life, this disease remains incurable," said Dr. Cho. "Immunotherapies have enormous potential in this patient population, and we hope the MAGE-A3 protein vaccine will bring us closer to a cure."
Patients with prostate cancer who do not respond to hormone therapy have varying rates of long-term survival, ranging from months to several years. To better predict survival in these patients, Mount Sinai researchers led by William K. Oh, MD, Chief of the Division of Hematology and Medical Oncology of The Tisch Cancer Institute, have created a whole-blood molecular biomarker and successfully identified a robust six-gene model. Using blood from 202 men, the research team determined which patients were high risk and died within 2.2 years, and which were lower risk, living beyond 2.2 years. Having a clear prognosis for these patients will help determine treatment course and clinical trial suitability. The genes noted in the model suggest possible changes in the immune system related to late-stage disease that warrant further study as a target for immune-based therapies.
"There is an urgent need for predictive models that help assess how aggressive the disease is in prostate cancer patients," said Dr. Oh. "Our six-gene model will allow clinicians to better determine the course of action for their patients, determine clinical trial eligibility, and lead to more targeted studies in late stage disease."
For patients with a type of head and neck cancer called oropharyngeal squamous cell cancer, determining whether the cancer is HPV-positive or negative is an important predictive factor in assessing clinical outcomes. A team of researchers led by Marshall Posner, MD, Professor of Medicine and Medical Director of the Head and Neck Oncology Center at Mount Sinai, analyzed 280 patients treated between 2002 and 2011: 201 with HPV-positive cancer and 79 with HPV-negative cancer. Of the 280 patients, 106 were treated with induction chemotherapy followed by chemoradiotherapy, and 174 were treated with chemoradiotherapy alone.
Patients with HPV-positive oropharyngeal squamous cell cancer treated with chemoradiotherapy alone had significantly better overall survival after three years ( 89.1 percent) and progression-free survival (81.7 percent) compared to HPV-negative patients (70.5 and 58.8 percent, respectively). The outcomes were similar in the induction chemotherapy plus chemoradiotherapy group, with a three-year overall survival rate of 89.7 percent in the HPV-positive group and 68.2 percent in the HPV-negative group.
"The dramatic increase in the incidence of HPV-positive head and neck cancer is concerning," said Dr. Posner. "However, our research indicates that these patients have a much better prognosis with standard treatments than the traditional 'smoker-drinker' head and neck cancer patient. At Mount Sinai, we are pursuing opportunities to reduce the toxicity and long term complications of therapy in HPV-positive patients."
PARADIGM is a multicenter, Phase III trial of 145 patients randomized to receive sequential therapy with three chemotherapy drugs or chemoradiotherapy, in which the drugs are delivered at the same time. The enrollment goal for PARADIGM was 300 patients, but patient accrual was stopped at 145 due to limited enrollment in U.S. sites. In the sequential therapy group, three-year survival was 73 percent and progression-free survival was 67 percent. In the chemoradiotherapy group, three-year survival was 78 percent and progression-free survival was 73 percent.
"Despite the early termination of PARADIGM, the results of treatment with sequential therapy and chemoradiotherapy are consistent," said Dr. Posner. "Excellent survival was seen in both treatment arms, a finding that warrants further study to help determine the best treatment course and tolerability of these therapies."
A research team found that the staging system used in soft tissue sarcomatumors that develop in tissues such as muscles, tendons, fat, or blood vesselswas inadequate in helping clinicians evaluate disease severity, undermining their ability to determine prognosis and treatment course. Led by Robert Maki, MD, PhD, Medical Director of the Sarcoma Medical Oncology Program and Chief of Pediatric Hematology and Oncology at Mount Sinai School of Medicine, researchers evaluated a database of more than 8,000 patients using the criteria of versions six and seven of a staging system created by the American Joint Committee on Cancer (AJCC).
They found that in both of these versions, tumor size is not adequately addressed in determining relapse-free and overall survival. Tumor depth appears to be a less important factor than previously considered, if the size characteristics are taken into account. Patients with lymph node involvement without other metastases fared statistically worse than patients with large, high-grade tumors without nodal metastasis, findings that are not addressed in either version of the staging system.
According to Dr. Maki and his team, the primary tumor site, histology, and a larger number of size categories are critical factors in learning disease prognosis. They suggest patient-specific nomograms, i.e. charts detailing tumor characteristics, or other techniques as a better predictive model.
"Our research shows that the staging system for soft tissue sarcomas requires significant modification, and that a single staging system for this complex tumor type does not suffice to determine patient prognosis," said Dr. Maki. "Newer techniques may be more accurate to determine prognosis, help communicate risk, and choose the ideal treatment."
First-line chemotherapy for most patients with metastatic bladder cancer includes a drug called cisplatin, but overall survival with this treatment varies. To better assess outcomes and survival, Mount Sinai researchers led by Matthew Galsky, MD, Assistant Professor, Hematology and Medical Oncology at Mount Sinai developed a predictive model for metastatic bladder cancer. They conducted a retrospective analysis of data from November, 1997, to October, 2010, of 361 patients who were enrolled in Phase II and III clinical trials, and found that functional status; metastases to the lung, liver, or bone; and elevated white blood cell counts were significantly associated with poor survival. Based on this finding, Dr. Galsky and his team developed a replicable formula to help clinicians predict patient outcomes, determine treatment course, and improve clinical trial design.
"We knew some of the variables that might contribute to survival in metastatic bladder cancer patients treated with cisplatin-based chemotherapy, but we wanted to validate those findings and develop a definitive predictive model for treatment outcomes," said Dr. Galsky. "The model we have constructed confirms these variables, provides clinicians with a measuring tool to calculate survival for each individual patient, and will help design better clinical trials in this patient population."
In 2001, two major studies were published showing that removing the kidney, called cytoreductive nephrectomy (CyNx), was an effective way to treat metastatic renal cell carcinoma (mRCC) in conjunction with immunotherapy. However, in 2005, a class of drugs called VEGFR tyrosine kinase inhibitors emerged as the first line treatment for mRCC, leaving clinicians uncertain of the role of CyNx.
A research team, led by Che-kai Tsao, MD, Chief Fellow, Hematology and Medical Oncology at Mount Sinai School of Medicine, analyzed a database of 2,780 patients with mRCC between 2001 and 2008 to determine patterns of CyNx use. Between 2001 and 2005, half of patients had CyNx, but in 2008, that number decreased to 38 percent. In addition, black or hispanic ethnicity, older age, male gender, and larger tumor size were associated with a decrease in the use of CyNx.
"Use of cytoreductive nephrectomy decreased after VEGFR tyrosine kinase inhibitors were approved, and potential demographic differences in its use may be a focus of future research," said Dr. Tsao. "Our research underscores the need for definitive data on the role of cytoreductive nephrectomy today, and results of ongoing randomized trials are needed to refine the role of this treatment modality."
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