Phase I clinical trials in 56 patients with thyroid cancer: the M. D. Anderson Cancer Center experience.

INTRODUCTION: Thyroid cancer is the most common endocrine malignancy. The outcomes of patients with relapsed thyroid cancer treated on early-phase clinical trials have not been systematically analyzed. PATIENTS AND METHODS: We reviewed the records of consecutive patients with metastatic thyroid cancer referred to the Phase I Clinical Trials Program from March 2006 to April 2008. Best response was assessed by Response Evaluation Criteria in Solid Tumors. RESULTS: Fifty-six patients were identified. The median age was 55 yr (range 35-79 yr). Of 49 patients evaluable for response, nine (18.4%) had a partial response, and 16 (32.7%) had stable disease for 6 months or longer. The median progression-free survival was 1.12 yr. With a median follow-up of 15.6 months, the 1-yr survival rate was 81%. In univariate analysis, factors predicting shorter survival were anaplastic histology (P = 0.0002) and albumin levels less than 3.5 g/dl (P = 0.05). Among 26 patients with tumor decreases, none died (median follow-up 1.3 yr), whereas 52% of patients with any tumor increase died by 1 yr (P = 0.0001). The median time to failure in our phase I clinical trials was 11.5 months vs. 4.1 months for the previous treatment (P = 0.04). CONCLUSION: Patients with advanced thyroid cancer treated on phase I clinical trials had high rates of partial response and prolonged stable disease. Time to failure was significantly longer on the first phase I trial compared with the prior conventional treatment. Patients with any tumor decrease had significantly longer survival than those with any tumor increase.

The role of smoking status on postoperative complications and survival in lung cancer patients presenting to M.D. Anderson Cancer Center

It is estimated that 50% of all lung cancer patients continue to smoke after diagnosis. Many of these lung cancer patients who are current smokers often experience tremendous guilt and responsibility for their disease, and feel it might be too late for them to quit smoking. In addition, many oncologists may be heard to say that it is 'too late', 'it doesn't matter', 'it is too difficult', 'it is too stressful' for their patients to stop smoking, or they never identify the smoking status of the patient. Many oncologists feel unprepared to address smoking cessation as part of their clinical practice. In reality, physicians can have tremendous effects on motivating patients, particularly when patients are initially being diagnosed with cancer. More information is needed to convince patients to quit smoking and to encourage clinicians to assist patients with their smoking cessation. ^ In this current study, smoking status at time of lung cancer diagnosis was assessed to examine its impact on complications and survival, after exploring the reliability of smoking data that is self-reported. Logistic Regression was used to determine the risks of smoking prior to lung resection. In addition, survival analysis was performed to examine the impact of smoking on survival. ^ The reliability of how patients report their smoking status was high, but there was some discordance between current smokers and recent quitters. In addition, we found that cigarette pack-year history and duration of smoking cessation were directly related to the rate of a pulmonary complication. In regards to survival, we found that current smoking at time of lung cancer diagnosis was an independent predictor of early stage lung cancer. This evidence supports the idea that it is "never too late" for patients to quit smoking and health care providers should incorporate smoking status regularly into their clinical practice.^

Survival of gastrointestinal and stromal tumor patients at UT M.D. Anderson Cancer Center

Objective. Gastrointestinal Stromal Tumors (GISTs) are rare mesenchymal tumors of the gastrointestinal (GI) tract with spindled cell, epithelioid, or occasionally pleomorphic morphology. The primary objective of this paper is to describe the demographic and clinical characteristics and survival among GIST patients registered at the University of Texas M.D. Anderson Cancer Center (MDACC). ^ Methods. This cohort study includes 783 consecutive patients diagnosed with GIST from 1995 to 2007. Demographic, clinical and survival information were obtained from the MDACC cancer registry. ^ Statistical Analysis. Kaplan-Meier survival curves, univariate and multivariate Cox proportional hazards analysis were conducted to estimate survival and identify prognostic clinical factors associated with survival. Results. The age at diagnosis of MDACC GIST cases ranged from 17 to 91 with a mean of 57 years and a male-to-female ratio of 1.3:1. The racial distribution was whites 77%, African-Americans 9.5%, Hispanics 9.3% and other races 4.2%. Fifty per cent of the GISTs arose from stomach, 35% small intestine, 7% retroperitoneal space, 6% colorectal and 2% were omentum and mesentery. About half of the tumors were less than 10 cm in size. Fifty eight per cent of the tumors were localized whereas 36% were metastatic. MDACC GIST patients were generally comparable to SEER patients, but, on the average, were 7 years younger than SEER patients and were predominantly whites. ^ Stratification of 783 GIST cases by year of diagnosis based on the introduction of imatinib treatment in 2000 revealed that 60% of the GIST cases were first diagnosed between 2000 and 2007 whereas, 40% were first diagnosed between 1995 and 1999. There was a significant difference between the two cohorts in the distribution of race, GIST symptom, tumor size, tumor site, and stage of the tumor at diagnosis. The 1- and 5-year survival was 93% and 59% in the 1995–2007 cohort. Multivariate Cox regression analysis identified age at diagnosis (p<0.001), female sex (p=0.047), tumor size (p=0.07), multiple cancers (p=0.002), and GIST diagnosed between 2000 and 2007 (p<0.001) were significantly associated with survival. Approximately, 58% of the cases were treated with imatinib whereas 42% did not receive imatinib in 2000–2005 cohort. There was a significant difference in survival between imatinib and non-imatinib groups and in the distribution of tumor size categories, stage of the tumor at diagnosis and cancers before the diagnosis of GIST. The 1- and 5-year survival for imatinib patients was 99% and 73% and was 91% and 63% for non-imatinib patients. Multivariate Cox regression analysis of the 2000–2007 cohort identified, age at diagnosis and tumor stage as possible prognostic factors associated with survival.^

Evaluation of epidemiological and clinical factors in survival of patients with de novo myelodysplastic syndrome at the University of Texas MD Anderson cancer center

Little is known about epidemiological markers that are associated with survival of patients with myelodysplastic syndromes (MDS). We conducted a secondary case-based analysis of 465 de novo MDS patients from the University of Texas MD Anderson Cancer Center (UTMDACC). We investigated the association between demographic as well as occupational exposure markers and survival while incorporating known clinical markers of prognosis. In our patient population, 60.6% were men and the majority were white (93.1%). The distribution of MDS subtypes by the French–American–British (FAB) classification was 81 (19%) refractory anemia (RA), 46 (9.9%) refractory anemia with ringed sideroblasts (RARS), 57 (12.3%) chronic myelomonocytic leukemia (CMML), 173 (37.2%) RA with excess blasts (RAEB), and 86 (18.5%) RAEB in transformation (RAEBT). We found that those older at diagnosis (> 60 years of age) (HR = 1.68, CI = 1.26-2.25) were at a higher risk of dying compared to younger patients. Similarly, high pack years of smoking (>= 30 pack years of smoking) (HR = 1.34, CI = 1.02-1.74), and agricultural chemical exposure (HR = 1.61, CI = 1.05-2.46) were significantly associated with overall lower survival when compared to patients with none or medium exposures. Among clinical markers, greater than 5% bone marrow blasts (HR = 1.81 CI = 1.27-2.56), poor cytogenetics (HR = 3.20, CI = 2.37-4.33)), and platelet cytopenias (<100000/ul) (HR = 1.46, CI = 1.11-1.92) were also significantly associated with overall MDS survival.^ The identification of epidemiological markers could help physicians stratify patients and customize treatment strategies to improve the outcome of MDS based on patient lifestyle information such as smoking exposure and agrochemical exposure. We hope that this study highlights the impact of these exposures in MDS prognosis.^

ACCURACY OF THE BRCAPRO RISK ASSESSMENT MODEL IN MALES PRESENTING TO MD ANDERSON FOR BRCA TESTING

ACCURACY OF THE BRCAPRO RISK ASSESSMENT MODEL IN MALES PRESENTING TO MD ANDERSON FOR BRCA TESTING Publication No. _______ Carolyn A. Garby, B.S. Supervisory Professor: Banu Arun, M.D. Hereditary Breast and Ovarian Cancer (HBOC) syndrome is due to mutations in BRCA1 and BRCA2 genes. Women with HBOC have high risks to develop breast and ovarian cancers. Males with HBOC are commonly overlooked because male breast cancer is rare and other male cancer risks such as prostate and pancreatic cancers are relatively low. BRCA genetic testing is indicated for men as it is currently estimated that 4-40% of male breast cancers result from a BRCA1 or BRCA2 mutation (Ottini, 2010) and management recommendations can be made based on genetic test results. Risk assessment models are available to provide the individualized likelihood to have a BRCA mutation. Only one study has been conducted to date to evaluate the accuracy of BRCAPro in males and was based on a cohort of Italian males and utilized an older version of BRCAPro. The objective of this study is to determine if BRCAPro5.1 is a valid risk assessment model for males who present to MD Anderson Cancer Center for BRCA genetic testing. BRCAPro has been previously validated for determining the probability of carrying a BRCA mutation, however has not been further examined particularly in males. The total cohort consisted of 152 males who had undergone BRCA genetic testing. The cohort was stratified by indication for genetic counseling. Indications included having a known familial BRCA mutation, having a personal diagnosis of a BRCA-related cancer, or having a family history suggestive of HBOC. Overall there were 22 (14.47%) BRCA1+ males and 25 (16.45%) BRCA2+ males. Receiver operating characteristic curves were constructed for the cohort overall, for each particular indication, as well as for each cancer subtype. Our findings revealed that the BRCAPro5.1 model had perfect discriminating ability at a threshold of 56.2 for males with breast cancer, however only 2 (4.35%) of 46 were found to have BRCA2 mutations. These results are significantly lower than the high approximation (40%) reported in previous literature. BRCAPro does perform well in certain situations for men. Future investigation of male breast cancer and men at risk for BRCA mutations is necessary to provide a more accurate risk assessment.