BACKGROUND: Brain metastasis is an uncommon, morbid complication of metastatic thyroid carcinoma. Because of its rarity, management often is problematic. To help contribute to the management of this disease entity, the authors present herein what to their knowledge is the largest series reported to date in which all patients had biopsy proven confirmation of their brain metastases.METHODS: The authors report a series of 16 patients with metastatic thyroid carcinoma to the brain who were treated between 1976–2000. The Mayo Clinic database was used to locate and review charts and radiology and pathology reports, and all biopsy specimens were reviewed by one pathologist. The histologic types of carcinoma included 10 papillary carcinomas, 2 follicular carcinomas, 1 Hürthle cell carcinoma, 1 medullary carcinoma, 1 insular carcinoma, and 1 anaplastic carcinoma. Given the small sample size, statistical analyses were not performed.RESULTS: Surgical resection of brain metastases was associated with a trend toward longer survival (20.8 months vs. 2.7 months for no surgical intervention in selected patients) Whole brain external beam radiation therapy produced disease regression in three of the four evaluable patients. Gamma knife radiosurgery and radioactive iodine therapy appear to play limited, but beneficial, therapeutic roles. Overall, survival after the diagnosis of brain metastasis is reported to be longer than that noted with other solid tumors (17.4 months), and the majority of patients die of their extracranial disease (85% in the current series).CONCLUSIONS: The results of the current study indicate that local therapies appear to control brain metastases in the large majority of thyroid carcinoma patients with metastases to the brain. Cancer 2003;98:356–62. © 2003 American Cancer Society.DOI 10.1002/cncr.11488

KRAS and BRAF^V600E mutations are important predictive and prognostic markers, respectively, in colon cancer, but little is known about patient and clinical factors associated with them. Two thousand three hundred twenty-six of 3397 patients in the N0147 phase III adjuvant trial for stage III colon cancer completed a patient questionnaire. Primary tumors were assessed for KRAS and BRAF^V600E mutations and defective mismatch repair (dMMR) status. Logistic regression models and categorical data analysis were used to identify associations of patient and tumor characteristics with mutation status. All statistical tests were two-sided. KRAS (35%) and BRAF^V600E (14%) mutations were nearly mutually exclusive. KRAS mutations were more likely to be present in patients without a family history of colon cancer and never smokers. Tumors with KRAS mutations were less likely to have dMMR (odds ratio [OR] = 0.21; 95% confidence interval [CI] = 0.15 to 0.31; P < .001) and high-grade histology (OR = 0.73; 95% CI = 0.59 to 0.92; P < .001) but were more often right-sided. Among KRAS -mutated tumors, those with a Gly13Asp mutation tended to have dMMR and high-grade histology. Tumors with BRAF^V600E mutations were more likely to be seen in patients who were aged 70 years or older (OR = 3.33; 95% CI = 2.50 to 4.42; P < .001) and current or former smokers (OR = 1.64; 95% CI = 1.26 to 2.14; P < .001) but less likely in non-whites and men. Tumors with BRAF^V600E mutations were more likely to be right-sided and to have four or more positive lymph nodes, high-grade histology, and dMMR. Specific patient and tumor characteristics are associated with KRAS and BRAF^V600E mutations.

Objectives While pancreatic cancer (PC) most often affects older adults, to date, there has been no comprehensive assessment of risk factors among PC patients younger than 60 years. Methods We defined early-onset PC (EOPC) and very-early-onset PC (VEOPC) as diagnosis of PC in patients younger than 60 and 45 years, respectively. We pooled data from 8 case-control studies, including 1954 patients with EOPC and 3278 age- and sex-matched control subjects. Logistic regression analysis was performed to identify associations with EOPC and VEOPC. Results Family history of PC, diabetes mellitus, smoking, obesity, and pancreatitis were associated with EOPC. Alcohol use equal to or greater than 26 g daily also was associated with increased risk of EOPC (odds ratio, 1.49; 95% confidence interval, 1.21–1.84), and there appeared to be a dose- and age-dependent effect of alcohol on risk. The point estimate for risk of VEOPC was an odds ratio of 2.18 (95% confidence interval, 1.17–4.09). Conclusions The established risk factors for PC, including smoking, diabetes, family history of PC, and obesity, also apply to EOPC. Alcohol intake appeared to have an age-dependent effect; the strongest association was with VEOPC.

Purpose: Targeting focal adhesion kinase (FAK) renders checkpoint immunotherapy effective in pancreatic ductal adenocarcinoma (PDAC) mouse model. Defactinib is a highly potent oral FAK inhibitor that has a tolerable safety profile. Patients and Methods: We conducted a multicenter, open-label, phase I study with dose escalation and expansion phases. In dose escalation, patients with refractory solid tumors were treated at five escalating dose levels of defactinib and gemcitabine to identify a recommended phase II dose (RP2D). In expansion phase, patients with metastatic PDAC who progressed on frontline treatment (refractory cohort) or had stable disease (SD) after at least 4 months of standard gemcitabine/nab-paclitaxel (maintenance cohort) were treated at RP2D. Pre- and posttreatment tumor biopsies were performed to evaluate tumor immunity. Results: The triple drug combination was well-tolerated, with no dose-limiting toxicities. Among 20 treated patients with refractory PDAC, the disease control rate (DCR) was 80%, with one partial response (PR) and 15 SDs, and the median progression-free survival (PFS) and overall survival (OS) were 3.6 and 7.8 months, respectively. Among 10 evaluable patients in the maintenance cohort, DCR was 70% with one PR and six SDs. Three patients with SD came off study due to treatment- or disease-related complications. The median PFS and OS on study treatment were 5.0 and 8.3 months, respectively. Conclusions: The combination of defactinib, pembrolizumab, and gemcitabine was well-tolerated and safe, had promising preliminary efficacy, and showed biomarker activity in infiltrative T lymphocytes. Efficacy of this strategy may require incorporation of more potent chemotherapy in future studies.

BACKGROUND: Higher body‐mass index (BMI) has been implicated as a risk factor for developing pancreatic cancer, but its effect on survival has not been thoroughly investigated. The authors assessed the association of BMI with survival in a sample of pancreatic cancer patients and used epidemiologic and clinical information to understand the contribution of diabetes and hyperglycemia.METHODS: A survival analysis using Cox proportional hazards by usual adult BMI was performed on 1861 unselected patients with pancreatic adenocarcinoma; analyses were adjusted for covariates that included clinical stage, age, and sex. Secondary analyses incorporated self‐reported diabetes and fasting blood glucose in the survival model.RESULTS: BMI as a continuous variable was inversely associated with survival from pancreatic adenocarcinoma (hazard ratio [HR], 1.019 for each increased unit of BMI [kg/m²], P < .001) after adjustment for age, stage, and sex. In analysis by National Institutes of Health BMI category, BMIs of 30 to 34.99 kg/m² (HR, 1.14; 95% confidence interval [CI], 0.98‐1.33), 35 to 39.99 kg/m² (HR 1.32, 95% CI 1.08‐1.62), and ≥40 (HR 1.60, 95% CI 1.26‐2.04) were associated with decreased survival compared with normal BMI of 18.5 to 24.99 kg/m² (overall trend test P < .001). Fasting blood glucose and diabetes did not affect the results.CONCLUSIONS: Higher BMI is associated with decreased survival in pancreatic cancer. Although the mechanism of this association remains undetermined, diabetes and hyperglycemia do not appear to account for the observed association. Cancer 2010. © 2010 American Cancer Society.