Experts from The Cancer Institute, an NCI-designated cancer center, at NYU Langone Medical Center presented new research findings at the 47th American Society of Clinical Oncology (ASCO) 2011 Annual Meeting in Chicago, IL. The conference was held June 3-7, 2011 and scientists from the NYU Cancer Institute discussed various new research findings in melanoma, breast cancer, head & neck cancer , prostate cancer and pediatric oncology including:
MelanomaIn a collaborative study, researchers analyzed DNA samples from a large group of individuals with and without a history of melanoma. Information regarding exposure to sunlight and indoor tanning equipment was also collected. In a publication from June 2010, these investigators demonstrated that an increased number of sunburns and exposure to indoor tanning devices were each associated with an increased risk of melanoma. This new study explored whether naturally occurring, inherited variations in a gene called MC1R affects an individual’s risk of developing melanoma. The MC1R gene helps determine hair color and skin pigmentation, and plays a role in the repair of DNA damage that is caused by ultraviolet light. Researchers also investigated whether individuals with certain MC1R variants were at higher risk of melanoma when exposed to sunlight or indoor tanning compared to others who lacked those genetic variants. In preliminary analysis researchers found that an increased number of sunburns, and exposure to indoor tanning, were each associated with a significantly increased risk of melanoma in all patients, whether or not they were found to have a variation in the MC1R gene. Patients with the greatest increase in risk, however, were those who had certain genetic variants known to play a role in red hair color and fair skin pigmentation. The likelihood of developing melanoma in patients with these high‐risk MC1R variants, compared to patients with no MC1R variants, was up to 3 times higher in those who suffered over 5 sunburns in their lifetime, and up to 5 times higher for those who spent 10 or more hours using indoor tanning devices over their lifetime. Interestingly, the melanoma risk associated with these genetic variants was still present after accounting for factors already known to be associated with melanoma risk, such as light hair and skin color. These preliminary results suggest all individuals have an increased risk of developing melanoma after outdoor sunburns or exposure to indoor tanning devices, and certain individuals may be genetically more vulnerable. Naturally occurring, inherited variations in the MC1R gene may be part of the biological basis of this increased predisposition for ultraviolet light‐induced melanoma.
A Population-Based, Case-Control Study of MC1R Variants, Ultraviolet Light Exposure, and Melanoma
An Analysis of Sera-Based MicroRNAs as Biomarkers of Recurrence in Melanoma
Identification of primary melanoma patients at high risk for recurrence is critical for informed management decisions. Given the advantage of non-invasive collection of blood, evidence of microRNA (miRNA) dysregulation in cancer and stability in serum, researchers hypothesized that the differential expression of miRNA in the serum could be a sensitive and a specific marker of melanoma. Researchers studied 146 melanoma patients with a minimum 3 years follow-up and 55 control individuals including healthy volunteers, patients with a systemic inflammatory condition and patients with other types of cancers. Melanoma patients were identified from a prospective melanoma database at NYU Langone Medical Center. Researchers combined a “discovery approach” using a PCR array platform and a “targeted approach” using a selection of 18 miRNAs based on a prior criteria. Researchers studied the prognostic relevance of miRNAs in a subset of 81 cases. Logistic regression modeling and the associated ROC analyses identified diagnostic miRNA signatures able to discriminate melanoma patients from all controls.
Abraxane, Temozolomide, and Oblimersen (The ATG Trial): A Final Report of Toxicity and Clinical Efficacy in Metastatic Melanoma Patients with Normal Lactate Dehydrogenase (LDH)
The combination of oblimersen (OBL), a bcl-2 anti-sense agent, with dacarbazine showed promise in metastatic melanoma patients with normal lactate dehydrogenase (nl LDH). OBL, temozolomide (TMZ), and abraxane (ABX) were synergistic in preclinical models of A375 metastatic melanoma cell lines. Researchers conducted a phase I trial of this combination in metastatic melanoma with nl LDH to analyze its toxicity and clinical efficacy. 32 patients were treated. Researchers concluded that the combination of OBL, TMZ, and ABX in metastatic melanoma patients with nl LDH is safe and well tolerated. The disease control rate of 78.1% and the survival data are encouraging. Biomarker studies support the rationale that Bcl-2 antisense therapy specifically impacts apoptotic signaling pathways in metastatic melanoma cells. The twice-weekly, fixed-dose OBL schedule appears to be similar in safety and efficacy as the 7-day CIV regimen.
Breast CancerPTC299, an oral investigational drug, suppresses tumor growth by selective posttranscriptional inhibition of tumor VEGF and angiogenic cytokine synthesis. Alone, PTC299 shows antitumor activity and intratumoral reduction in VEGF synthesis in both hormone receptor-positive and -negative breast cancer (BC) xenografts. Alone or in combination with letrozole, PTC299 eliminates tumors in aromatase-overexpressing human BC xenografts. Researchers report effects of PTC299 + aromatase inhibitors (AIs) on human serum VEGF (sVEGF) and IL-6 in patients with metastatic breast cancer (mBC). In the study Stage 2 of a Phase Ib study combining PTC299 + AI therapy is reported. Women with 1st or 2nd line HR+ mBC currently receiving or newly initiating an AI receive concurrent PTC299 100 mg BID po until progressive disease (PD). sVEGF and IL-6 levels are obtained Days 1 (D1) and 42 (D42). PTC299 + AIs is shown to be generally well tolerated, shows clinical activity, and reduces sVEGF and IL-6 in patients elevated at D1. The study results provide preliminary support for the proposed mechanism of action that PTC299 inhibits production of tumor VEGF and other angiogenic cytokines with unchanged physiological VEGF production.
Reduction of Serum VEGF and IL-6 levels in Patients with Metastatic Breast Cancer: Results of a Study of PTC299, an Oral Inhibitor of Tumor VEGF Synthesis, and Aromatase Inhibitors
Prostate CancerRacial disparities persist in curative therapy (CTx) for clinically localized prostate cancer (CaP). This study explores disparities across strata of treatment appropriateness as defined by potential for clinical benefit. Using the SEER-Medicare dataset, researchers identified 64,192 men (54,420 white and 5,933 black) aged 67-85 years diagnosed with localized CaP 1996-2005. CTx was defined as either radical prostatectomy or radiation. Approximately 66% of white and 56% of black patients received CTx. Although black patients were significantly less likely to receive CTx in each benefit group, the magnitude of the racial disparity varied with the degree of potential clinical benefit. In the low benefit group, the adjusted predicted probability of receipt of CTx was 44% for black compared to 48% for white patients, 58% vs. 69% in the intermediate group, and 65% vs. 81% in the highest benefit group. The largest racial disparity existed in the highest benefit group (adjusted odds ratio (OR) for CTx for black vs. white patients 0.57; 95% CI: 0.49, 0.65); among patients in the low benefit group, the OR for black vs. white patients was 0.77; 95% CI: 0.68,0.88. The interaction between race and clinical benefit group was significant. Researchers concluded the magnitude of racial disparities in the receipt of CTx for CaP varies substantially according to clinical benefit. Improving racial disparities should focus on increasing CTx of black CaP patients of the highest clinical benefit.
Racial Disparities in Prostate Cancer Treatment: The Contribution of Inappropriate Care
Head and Neck CancerLong-term maintenance therapy with Pegylated Liposomal Doxorubicin (PLD) has been explored as a treatment for relapsed ovarian cancer. Researchers monitored a cohort of patients on this therapy for side effects and secondary malignancies. Researchers report on four patients receiving long-term PLD for advanced stage ovarian cancer who developed malignant and/or pre-malignant lesions of the tongue and/or oral cavity. All four patients had received maintenance therapy with PLD for periods of at least three years. Three patients were diagnosed with squamous cell carcinoma (SCC) of the tongue and/or oral cavity, and one with sublingual mucosa high-grade dysplasia. Noteworthy was a patient with three separate SCCs of the oral cavity. Three of the four patients had deleterious BRCA mutations. None of the patients were former smokers. The study shows secondary cancer of the oral cavity followed long-term PLD treatment of patients with recurrent ovarian cancer. These findings have implications on surveillance and preventative measures for this population.
Multiple Cases of Squamous Cell Carcinoma of the Tongue and Oral Cavity in Patients Treated with Long-Term Pegylated Liposomal Doxorubicin (PLD) for Ovarian Cancer
Exploring Factors in Diagnostic Delays of Head and Neck Cancer at a Public Hospital
Diagnosis and management of squamous cell carcinoma of the head and neck (SCCHN) involves a multidisciplinary approach. Navigation through a public hospital and the involved services often results in frequent diagnostic delays. Researcher set out to quantify “provider delay:” the time between the first contact with health care provider and the time the diagnosis was confirmed by biopsy and determine what factors influence the delay in diagnosis. Researchers extracted data from patients diagnosed with SCCHN in the years of 2007 to 2009 and performed univariate analysis to examine associations between provider delay and the following characteristics: language (English or Non-English), employment, presence of partner, gender, ethnicity, age, cancer subsite, staging, number of co-morbidities (≤3 or >3 conditions), number of tobacco pack-years, and history of alcohol dependence. Researchers retrieved data on 117 SCCHN patients diagnosed in the years 2007 to 2009. The mean provider delay for all patients was 67.3 days, with a standard deviation of 116. There was a significant difference in two characteristics. Provider delay was significantly shorter for non-English speakers than English speakers. In addition, there was a trend of shorter provider delay when patients were unemployed compared to patients with employment. Researchers found no significant associations between provider delay and the other variables listed above. These results counter the notion that the lack of English literacy and unemployment present disadvantages to the patient. Researchers hypothesize that shorter provider delays are seen in non-English speakers because they have better social support and provider delay is dissimilar in different subsets of patients suggests that this delay is amenable to interventions. Future analyses will focus on the role of social support and interventions to reduce provider delay.
Pediatric OncologyAlthough EFS continues to improve for children and young adults with High-Risk Acute Lymphoblastic Leukemia (HR-ALL), central nervous system (CNS) disease has become an increasing site of treatment failure. AALL0232 was designed to test the safety and efficacy of interventions targeted to enhance CNS control including comparisons of HD-MTX versus Capizzi escalating methotrexate plus PEG asparaginase (C-MTX/ASNase) during Interim Maintenance-1 (IM-1) and dexamethasone (DEX) versus prednisone (PRED) during Induction. AALL0232 was a Phase 3, randomized trial for patients 1-30 years old with newly diagnosed NCI high risk B-precursor ALL that utilized a 2 x 2 factorial design with an augmented intensity Berlin-Frankfurt-Münster (BFM) backbone. Patients were randomized to receive DEX versus PRED during Induction and HD-MTX (5gm/m2 biweekly x 4) versus C-MTX/ASNase during IM-1.
Comparison of High-Dose Methotrexate (HD-MTX) with Capizzi Methotrexate Plus Asparaginase (C-MTX/ASNase) in Children and Young Adults with High-Risk Acute Lymphoblastic Leukemia (HR-ALL): A report from the Children’s Oncology Group Study AALL023
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