Karen Ruth

A COMPARISON OF ACUTE AND CHRONIC TOXICITY FOR MEN WITH LOW-RISK PROSTATE CANCER TREATED WITH INTENSITY-MODULATED RADIATION THERAPY OR 125I PERMANENT IMPLANT

PURPOSE To compare the toxicity and biochemical outcomes of intensity-modulated radiation therapy (IMRT) and (125)I transperineal permanent prostate seed implant ((125)I) for patients with low-risk prostate cancer. METHODS AND MATERIALS Between 1998 and 2004, a total of 374 low-risk patients (prostate-specific antigen < 10 ng/ml, T1c-T2b, Gleason score of 6 or less, and no neoadjuvant hormones) were treated at Fox Chase Cancer Center (216 IMRT and 158 (125)I patients). Median follow-up was 43 months for IMRT and 48 months for (125)I. The IMRT prescription dose ranged from 74-78 Gy, and (125)I prescription was 145 Gy. Acute and late gastrointestinal (GI) and genitourinary (GU) toxicity was recorded by using a modified Radiation Therapy Oncology Group scale. Freedom from biochemical failure was defined by using the Phoenix definition (prostate-specific antigen nadir + 2.0 ng/ml). RESULTS Patients treated by using IMRT were more likely to be older and have a higher baseline American Urological Association symptom index score, history of previous transurethral resection of the prostate, and larger prostate volumes. On multivariate analysis, IMRT was an independent predictor of lower acute and late Grade 2 or higher GU toxicity and late Grade 2 or higher GI toxicity. Three-year actuarial estimates of late Grade 2 or higher toxicity were 2.4% for GI and 3.5% for GU by using IMRT compared with 7.7% for GI and 19.2% for GU for (125)I, respectively. Four-year actuarial estimates of freedom from biochemical failure were 99.5% for IMRT and 93.5% for (125)I (p = 0.09). CONCLUSIONS The IMRT and (125)I produce similar outcomes, although IMRT appears to have less acute and late toxicity.

Time to Surgery and Breast Cancer Survival in the United States.

IMPORTANCE Time to surgery (TTS) is of concern to patients and clinicians, but controversy surrounds its effect on breast cancer survival. There remains little national data evaluating the association. OBJECTIVE To investigate the relationship between the time from diagnosis to breast cancer surgery and survival, using separate analyses of 2 of the largest cancer databases in the United States. DESIGN, SETTING, AND PARTICIPANTS Two independent population-based studies were conducted of prospectively collected national data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database and the National Cancer Database (NCDB). The SEER-Medicare cohort included Medicare patients older than 65 years, and the NCDB cohort included patients cared for at Commission on Cancer-accredited facilities throughout the United States. Each analysis assessed overall survival as a function of time between diagnosis and surgery by evaluating 5 intervals (≤30, 31-60, 61-90, 91-120, and 121-180 days) and disease-specific survival at 60-day intervals. All patients were diagnosed with noninflammatory, nonmetastatic, invasive breast cancer and underwent surgery as initial treatment. MAIN OUTCOMES AND MEASURES Overall and disease-specific survival as a function of time between diagnosis and surgery, after adjusting for patient, demographic, and tumor-related factors. RESULTS The SEER-Medicare cohort had 94 544 patients 66 years or older diagnosed between 1992 and 2009. With each interval of delay increase, overall survival was lower overall (hazard ratio [HR], 1.09; 95% CI, 1.06-1.13; P < .001), and in patients with stage I (HR, 1.13; 95% CI, 1.08-1.18; P < .001) and stage II disease (HR 1.06; 95% CI, 1.01-1.11; P = .01). Breast cancer-specific mortality increased with each 60-day interval (subdistribution hazard ratio [sHR], 1.26; 95% CI, 1.02-1.54; P = .03). The NCDB study evaluated 115 790 patients 18 years or older diagnosed between 2003 and 2005. The overall mortality HR was 1.10 (95% CI, 1.07-1.13; P < .001) for each increasing interval, significant in stages I (HR, 1.16; 95% CI, 1.12-1.21; P < .001) and II (HR, 1.09; 95% CI, 1.05-1.13; P < .001) only, after adjusting for demographic, tumor, and treatment factors. CONCLUSIONS AND RELEVANCE Greater TTS is associated with lower overall and disease-specific survival, and a shortened delay is associated with benefits comparable to some standard therapies. Although time is required for preoperative evaluation and consideration of options such as reconstruction, efforts to reduce TTS should be pursued when possible to enhance survival.

Preoperative Delays in the US Medicare Population With Breast Cancer

PURPOSE Although no specific delay threshold after diagnosis of breast cancer has been demonstrated to affect outcome, delays can cause anxiety, and surgical waiting time has been suggested as a quality measure. This study was performed to determine the interval from presentation to surgery in Medicare patients with nonmetastatic invasive breast cancer who did not receive neoadjuvant chemotherapy and factors associated with a longer time to surgery. METHODS Medicare claims linked to Surveillance, Epidemiology, and End Results data were reviewed for factors associated with delay between the first physician claim for a breast problem and first therapeutic surgery. RESULTS Between 1992 and 2005, 72,586 Medicare patients with breast cancer had a median interval (delay) between first physician visit and surgery of 29 days, increasing from 21 days in 1992 to 32 days in 2005. Women (29 days v 24 days for men; P < .001), younger patients (29 days; P < .001), blacks and Hispanics (each 37 days; P < .001), patients in the northeast (33 days; P < .001), and patients in large metropolitan areas (32 days; P < .001) had longer delays. Patients having breast conservation and mastectomies had adjusted median delays of 28 and 30 days, respectively, with simultaneous reconstruction adding 12 days. Preoperative components, including imaging modalities, biopsy type, and clinician visits, were also each associated with a specific additional delay. CONCLUSION Waiting times for breast cancer surgery have increased in Medicare patients, and measurable delays are associated with demographics and preoperative evaluation components. If such increases continue, periodic assessment may be required to rule out detrimental effects on outcomes.

Phase II Study of Paclitaxel, Carboplatin, and Cetuximab as First Line Treatment, for Patients with Advanced Non-small Cell Lung Cancer (NSCLC): Results of OPN-017

Background: Cetuximab has demonstrated synergy with taxanes in preclinical models; as well as single agent activity. We assessed the activity of cetuximab with carboplatin and paclitaxel given on a 4-week schedule, in advanced, chemo-naive non-small cell lung cancer. Patients and Methods: This phase II, single arm, multi-institution study featured standard dosage of cetuximab 400 mg/m2 day 1, then 250 mg/m2 with paclitaxel (100 mg/m2/wk, for 3 weeks), and carboplatin (area under curve = 6) day 1 of each 28 day cycle. After 4 to 6 cycles, in the absence of disease progression or excess toxicity, cetuximab was continued weekly. Primary end point was response rate. Results: Fifty-three patients (median age 63, 51% male) participated. Response rate was 57% (3 complete response and 27 partial response). At a median follow-up of 12.5 months, the estimated overall survival is 13.8 months (95% CI: 9.08–16.02) with an event-free survival rate of 5.53 months (95% CI: 4.77–7.99), 18.9% remain free from progression at 1 year. Improved survival was associated with female gender, absence of prior radiation, PS 0 and epidermal growth factor receptor expression. Toxicities included rash (28% grade 3), nail changes (3.7% grade 3), hypomagnesemia (7.5% grade 3 and 3.7% grade 4), and neutropenia (25% grade 3 and 13% grade 4) in addition to other typical side effects anticipated with paclitaxel/carboplatin. There were no grade 5 toxicities. Conclusion: Combination of cetuximab/paclitaxel/carboplatin in non-small cell lung cancer was well tolerated and clinically active with manageable toxicities. This unique schedule, integrating weekly paclitaxel and cetuximab has not yet been tested in a randomized trial.

Race, Genetic West African Ancestry, and Prostate Cancer Prediction by Prostate-Specific Antigen in Prospectively Screened High-Risk Men

“Race-specific” prostate-specific antigen (PSA) needs evaluation in men at high risk for prostate cancer for optimizing early detection. Baseline PSA and longitudinal prediction for prostate cancer were examined by self-reported race and genetic West African (WA) ancestry in the Prostate Cancer Risk Assessment Program, a prospective high-risk cohort. Eligibility criteria were age 35 to 69 years, family history of prostate cancer, African American race, or BRCA1/2 mutations. Biopsies were done at low PSA values (<4.0 ng/mL). WA ancestry was discerned by genotyping 100 ancestry informative markers. Cox proportional hazards models evaluated baseline PSA, self-reported race, and genetic WA ancestry. Cox models were used for 3-year predictions for prostate cancer. Six hundred forty-six men (63% African American) were analyzed. Individual WA ancestry estimates varied widely among self-reported African American men. Race-specific differences in baseline PSA were not found by self-reported race or genetic WA ancestry. Among men with ≥1 follow-up visit (405 total, 54% African American), 3-year prediction for prostate cancer with a PSA of 1.5 to 4.0 ng/mL was higher in African American men with age in the model (P = 0.025) compared with European American men. Hazard ratios of PSA for prostate cancer were also higher by self-reported race (1.59 for African American versus 1.32 for European American, P = 0.04). There was a trend for increasing prediction for prostate cancer with increasing genetic WA ancestry. “Race-specific” PSA may need to be redefined as higher prediction for prostate cancer at any given PSA in African American men. Large-scale studies are needed to confirm if genetic WA ancestry explains these findings to make progress in personalizing prostate cancer early detection.

Lymphopenia is an Independent Predictor of Inferior Outcome in Clear Cell Renal Carcinoma

PURPOSE A low absolute lymphocyte count is a likely index of poor systemic immunity that may be associated with aggressive features and inferior survival in patients with clear cell renal cell carcinoma. MATERIALS AND METHODS To determine the absolute lymphocyte count we retrospectively analyzed the preoperative blood count of 430 patients with a mean age of 60 years treated with primary surgical resection at our cancer center. Absolute lymphocyte count values as a continuous variable and at a level below 1,300 cells per μl, which was our lowest reference value, were correlated with nuclear grade, pathological stage and TNM stage. We used the Kaplan-Meier method to estimate overall survival, stratified by absolute lymphocyte count status. RESULTS As a continuous variable, low absolute lymphocyte count was associated with higher grade (p = 0.009), and higher pT stage (p = 0.034) and TNM stage (p <0.0001). Lymphopenia below 1,300 cells per μl was associated with high grade (p = 0.0043), pT stage (p = 0.051) and TNM stage (p <0.0001). At a median followup of 33.5 months lymphopenia was associated with inferior overall survival in a univariate model (p <0.0001), and on multivariate analysis independent of pT, N and M stages, patient age, grade, smoking history and comorbidities (p = 0.0102). Lymphopenia was also associated with inferior overall survival in a subset of young patients (age 60 years or less) with no distant metastasis (p = 0.014). CONCLUSIONS In 430 patients with clear cell renal cell carcinoma lymphopenia was associated with lower overall survival independent of pT and TNM stages, nuclear grade, age, tobacco smoking and comorbidity index.

Radiotherapy Doses of 80 Gy and Higher Are Associated With Lower Mortality in Men With Gleason Score 8 to 10 Prostate Cancer

PURPOSE Men with Gleason score (GS) 8-10 prostate cancer (PCa) are assumed to have a high risk of micrometastatic disease at presentation. However, local failure is also a major problem. We sought to establish the importance of more aggressive local radiotherapy (RT) to ≥80 Gy. METHODS AND MATERIALS There were 226 men treated consecutively with RT ± ADT from 1988 to 2002 for GS 8-10 PCa. Conventional, three-dimensional conformal or intensity-modulated (IM) RT was used. Radiation dose was divided into three groups: (1) <75 Gy (n = 50); (2) 75-79.9 Gy (n = 60); or (3) ≥80 Gy (n = 116). The endpoints examined included biochemical failure (BF; nadir + 2 definition), distant metastasis (DM), cause-specific mortality, and overall mortality (OM). RESULTS Median follow-up was 66, 71, and 58 months for Groups 1, 2, and 3. On Fine and Grays competing risk regression analysis, significant predictors of reduced BF were RT dose ≥80 Gy (p = 0.011) and androgen deprivation therapy duration ≥24 months (p = 0.033). In a similar model of DM, only RT dose ≥80 Gy was significant (p = 0.007). On Cox regression analysis, significant predictors of reduced OM were RT dose ≥80 Gy (p = 0.035) and T category (T3/4 vs. T1, p = 0.041). Dose was not a significant determinant of cause-specific mortality. Results for RT dose were similar in a model with RT dose and ADT duration as continuous variables. CONCLUSION The results indicate that RT dose escalation to ≥80 Gy is associated with lower risks of BF, DM, and OM in men with GS 8-10 PCa, independently of androgen deprivation therapy.

p16 status, pathologic and clinical characteristics, biomolecular signature, and long‐term outcomes in head and neck squamous cell carcinomas of unknown primary

The purpose of this study was to report associations between p16 status, clinicopathologic characteristics, and outcomes for head and neck squamous cell carcinoma of unknown primary (CUP).

Risk for unplanned hospital readmission of patients with cancer: results of a retrospective medical record review.

PURPOSE/OBJECTIVES To identify potential factors that place patients with cancer at risk for unplanned readmissions after discharge from the hospital. DESIGN Retrospective, descriptive, medical record review. SETTING A National Cancer Institute-designated comprehensive cancer center in an urban area of the Northeastern United States. SAMPLE 78 patients were selected from those readmitted within seven days of discharge. For each readmission case, a nonreadmitted patient was randomly selected and matched on discharge date and reason for prior admission. The age range was 22-87 years, men and women were equally represented, and 88% were Caucasian. METHODS The Readmission Criteria Record was developed to collect data from medical records about factors associated with readmission, including demographics, severity of illness, support at home, symptoms, and comorbidities. MAIN RESEARCH VARIABLES Criteria associated with readmission risk. FINDINGS Patients who had gastrointestinal cancer, nausea within 24 hours of discharge, financial and insurance concerns, or caregiver difficulty or those who lived alone were more likely to be readmitted within seven days of discharge. Patients were more likely to be readmitted on Friday than any other day. Among readmitted patients, 48% were readmitted within one to two days postdischarge. CONCLUSIONS Knowledge of factors that may place patients with cancer at an increased risk for readmission and subsequent implementation of appropriate interventions during hospitalization may help to decrease risk of readmission. IMPLICATIONS FOR NURSING The factors identified provide a basis for assessment, planning, interventions, and follow-up of patients to help reduce the risk of readmission and, thus, poor outcomes.

Intention to communicate BRCA1/BRCA2 genetic test results to the family.

Guided by the theory of planned behavior, this analysis explores the communication skills of women who had genetic testing for BRCA1 and BRCA2. The key outcome was intention to tell test results to adult first-degree relatives. The theory predicts that global and specific attitudes, global and specific perceived social norms, and perceived control will influence the communication of genetic test results. A logistic regression model revealed that global attitude (p < .05), specific social influence (p < .01), and perceived control (p < .05) were significant predictors of intention to tell. When gender and generation of relatives were added to the regression, participants were more likely to convey genetic test results to female than to male relatives (p < .05) and were also more likely to communicate test results to children (p < .01) or siblings (p < .05) than to parents. However, this association depended on knowing the relatives opinion of genetic testing. Intention to tell was lowest among participants who did not know their relatives opinion. These results extend the theory of planned behavior by showing that gender and generation influence intention when the relatives opinion is unknown.