Carla L. Warneke

Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates.

Introduction: Osteonecrosis of the jaw (ONJ) has been reported in patients treated with bisphosphonates. The incidence and risk factors associated with this disorder have not been clearly defined.

Psychological Adjustment and Sleep Quality in a Randomized Trial of the Effects of a Tibetan Yoga Intervention in Patients with Lymphoma

Research suggests that stress‐reduction programs tailored to the cancer setting help patients cope with the effects of treatment and improve their quality of life. Yoga, an ancient Eastern science, incorporates stress‐reduction techniques that include regulated breathing, visual imagery, and meditation as well as various postures. The authors examined the effects of the Tibetan yoga (TY) practices of Tsa lung and Trul khor, which incorporate controlled breathing and visualization, mindfulness techniques, and low‐impact postures in patients with lymphoma.

Specific Mutations in the β-Catenin Gene (CTNNB1) Correlate with Local Recurrence in Sporadic Desmoid Tumors

Desmoid fibromatosis is a rare, nonmetastatic neoplasm marked by local invasiveness and relentless recurrence. Molecular determinants of desmoid recurrence remain obscure. beta-Catenin deregulation has been commonly identified in sporadic desmoids although the incidence of CTNNB1 (the gene encoding beta-catenin) mutations is uncertain. Consequently, we evaluated the prevalence of CTNNB1 mutations in a large cohort of sporadic desmoids and examined whether mutation type was relevant to desmoid outcome. Desmoid specimens (195 tumors from 160 patients, 1985 to 2005) and control dermal scars were assembled into a clinical data-linked tissue microarray. CTNNB1 genotyping was performed on a 138-sporadic desmoid subset. Immunohistochemical scoring was performed per standard criteria and data were analyzed using Kaplan-Meier and other indicated methods. CTNNB1 mutations were observed in 117 of 138 (85%) of desmoids. Three discrete mutations in two codons of CTNNB1 exon 3 were identified: 41A (59%), 45F (33%), and 45P (8%, excluded from further analysis because of rarity). Five-year recurrence-free survival was significantly poorer in 45F-mutated desmoids (23%, P < 0.0001) versus either 41A (57%) or nonmutated tumors (65%). Nuclear beta-catenin expression was observed in 98% of specimens and intensity was inversely correlated with incidence of desmoid recurrence (P < 0.01). In conclusion, CTNNB1 mutations are highly common in desmoid tumors. Furthermore, patients harboring CTNNB1 (45F) mutations are at particular risk for recurrence and therefore may especially benefit from adjuvant therapeutic approaches.

Clinical Correlates of NRAS and BRAF Mutations in Primary Human Melanoma

Purpose:NRAS and BRAF mutations are common in cutaneous melanomas, although rarely detected mutually in the same tumor. Distinct clinical correlates of these mutations have not been described, despite in vitro data suggesting enhanced oncogenic effects. This study was designed to test the hypothesis that primary human cutaneous melanomas harboring mutations in NRAS or BRAF display a more aggressive clinical phenotype than tumors wild type at both loci. Experimental Design: Microdissection of 223 primary melanomas was carried out, followed by determination of the NRAS and BRAF mutational status. Genotypic findings were correlated with features known to influence tumor behavior including age, gender, Breslow depth, Clark level, mitotic rate, the presence of ulceration, and American Joint Committee on Cancer (AJCC) staging. Results: Breslow depth and Clark level varied significantly among the genotypes, with NRAS mutants showing the deepest levels and wild-type tumors the least depth. Ulceration also differed significantly among the genotypes, with BRAF mutants demonstrating the highest rate. In addition, tumors with mutated NRAS were more likely to be located on the extremities. Patients whose tumors carried either mutation presented with more advanced AJCC stages compared with patients with wild-type tumors, and specifically, were more likely to have stage III disease at diagnosis. Overall survival did not differ among the 3 groups. Conclusions: Distinct clinical phenotypes exist for melanomas bearing NRAS and BRAF mutations, whether considered together or separately, and are associated with features known to predict aggressive tumor behavior. The impact of these mutations is most evident at earlier stages of disease progression. Clin Cancer Res; 17(2); 229–35. ©2010 AACR. Clin Cancer Res; 17(2); 229–35. ©2010 AACR.

A pilot study of the effects of expressive writing on psychological and behavioral adjustment in patients enrolled in a Phase II trial of vaccine therapy for metastatic renal cell carcinoma.

Forty-two patients with metastatic renal cell carcinoma who were participating in a Phase II clinical trial were randomly assigned to an expressive writing (EW) or neutral writing (NW) group. Patients in the EW group wrote about their cancer, and patients in the NW group wrote about health behaviors. No statistically significant group differences were found in symptoms of distress, perceived stress, or mood disturbance, except for the Vigor subscale of the Profile of Mood States. However, patients in the EW group reported significantly less sleep disturbance, better sleep quality and sleep duration, and less daytime dysfunction compared with patients in the NW group. The results suggest that EW may have sleep-related health benefits in terminally ill cancer patients.

Relationship Between Obesity and Pathologic Response to Neoadjuvant Chemotherapy Among Women With Operable Breast Cancer

PURPOSE To understand the mechanism through which obesity in breast cancer patients is associated with poorer outcome, we evaluated body mass index (BMI) and response to neoadjuvant chemotherapy (NC) in women with operable breast cancer. PATIENTS AND METHODS From May 1990 to July 2004, 1,169 patients were diagnosed with invasive breast cancer at M. D. Anderson Cancer Center and received NC before surgery. Patients were categorized as obese (BMI >or= 30 kg/m(2)), overweight (BMI of 25 to < 30 kg/m(2)), or normal/underweight (BMI < 25 kg/m(2)). Logistic regression was used to examine associations between BMI and pathologic complete response (pCR). Breast cancer-specific, progression-free, and overall survival times were examined using the Kaplan-Meier method and Cox proportional hazards regression analysis. All statistical tests were two-sided. RESULTS Median age was 50 years; 30% of patients were obese, 32% were overweight, and 38% were normal or underweight. In multivariate analysis, there was no significant difference in pCR for obese compared with normal weight patients (odds ratio [OR] = 0.78; 95% CI, 0.49 to 1.26). Overweight and the combination of overweight and obese patients were significantly less likely to have a pCR (OR = 0.59; 95% CI, 0.37 to 0.95; and OR = 0.67; 95% CI, 0.45 to 0.99, respectively). Obese patients were more likely to have hormone-negative tumors (P < .01), stage III tumors (P < .01), and worse overall survival (P = .006) at a median follow-up time of 4.1 years. CONCLUSION Higher BMI was associated with worse pCR to NC. In addition, its association with worse overall survival suggests that greater attention should be focused on this risk factor to optimize the care of breast cancer patients.

Upfront, Randomized, Phase 2 Trial of Sorafenib Versus Sorafenib and Low-Dose Interferon Alfa in Patients With Advanced Renal Cell Carcinoma: Clinical and Biomarker Analysis

The objective of this study was to independently evaluate the objective response rate of sorafenib and sorafenib plus low‐dose interferon‐alfa 2b (IFN) as frontline therapy in patients with metastatic renal cell carcinoma (mRCC).

Intake of Soft Drinks, Fruit-Flavored Beverages, and Fruits and Vegetables by Children in Grades 4 Through 6

Soft drinks supply about 20% to 24% of calories for 2- to 19-year-olds1 and contribute to excess calorie consumption2–4 and tooth decay.5 Noncarbonated sports drinks and fruit drinks also provide sugar and calories. The average American consumed 55.9 gallons of soft drinks and 6.1 gallons of fruit drinks in 1999.6 Soft drink consumption was negatively related to milk and fruit juice consumption,3 but the relationship between beverage consumption and consumption of other food groups is unknown. Here we describe the intake of sweetened beverages, fruits, vegetables, and calories by children in grades 4 through 6.

Primary cutaneous apocrine carcinoma: A clinico-pathologic analysis of 24 cases

Primary cutaneous apocrine carcinoma is a rare malignancy. This study of 24 examples suggests that the prognosis is not always poor and that grading criteria devised for breast carcinoma may have utility in this group of malignancies. Furthermore, steroid receptor expression should be investigated in these tumors, particularly if a tumor is unlikely to be controlled by surgery alone.

Impact of aspirin therapy in cancer patients with thrombocytopenia and acute coronary syndromes

Patients with cancer who have thrombocytopenia may experience acute coronary syndromes (ACS), and the use of aspirin (ASA) poses an increased risk of bleeding. The purpose of this study was to test the hypothesis that the benefit of ASA therapy in the treatment of ACS would extend to cancer patients with thrombocytopenia and outweigh the risks of severe bleeding.