Kerry L. Kilbridge

Quality-of-Life–Adjusted Survival Analysis of High-Dose Adjuvant Interferon Alfa-2b for High-Risk Melanoma Patients Using Intergroup Clinical Trial Data

PURPOSE High-dose adjuvant interferon alpha-2b (IFN alpha 2b) for high-risk melanoma is a 1-year regimen that improves relapse-free and overall survival but has significant toxicity. A quality-of-life--adjusted survival (QAS) analysis analysis of two cooperative group phase III trials, E1684 and E1690/S9111/C9190, was performed, incorporating patient values (utilities) for the toxicity of IFN alpha 2b treatment and melanoma recurrence. PATIENTS AND METHODS Quality-Adjusted Time Without Symptoms or Toxicity methodology was used with melanoma patient utilities and trial data to estimate the effect of IFN alpha 2b on QAS. The increase or decrease in QAS that patients could expect from treatment was estimated based on their utilities. Eleven utility predictor questions were tested to identify patients with utilities that result in decreased QAS. RESULTS Using E1684 data, IFN alpha 2b would result in an increase in QAS for all sets of patient utilities. This benefit was significant (P <.05) for 16% of patients. Using E1690/S9111/C9190 data, 77% of patients would experience a benefit in QAS from IFN alpha 2b and 23% would experience a decrease in QAS; neither of these effects was statistically significant. Using utility predictors and the E1690/S9111/C9190 analysis, a decision rule was formulated that helps identify patients in whom IFN alpha 2b may detract from QAS. CONCLUSION Most patients experienced improvement in QAS in both trials, but this benefit was statistically significant in only 16% of patients in E1684. Change in QAS depends more on the utility for IFN alpha 2b toxicity than on the utility for melanoma recurrence. Cancer patients probably have higher utilities for IFN alpha 2b toxicity than members of the general population and will tend to favor IFN alpha 2b treatment as a result.

Patient Preferences for Adjuvant Interferon Alfa-2b Treatment

PURPOSE Although trials of adjuvant interferon alfa-2b (IFN alpha-2b) in high-risk melanoma patients suggest improvement in disease-free survival, it is unclear whether treatment offers improvement in overall survival. Widespread use of adjuvant IFN alpha-2b has been tempered by its significant toxicity. To quantify the trade-offs between IFN alpha-2b toxicity and survival, we assessed patient utilities for health states associated with IFN therapy. Utilities are measures of preference for a particular health state on a scale of 0 (death) to 1 (perfect health). PATIENTS AND METHODS We assessed utilities for health states associated with adjuvant IFN among 107 low-risk melanoma patients using the standard gamble technique. Health states described four IFN alpha-2b toxicity scenarios and the following three posttreatment outcomes: disease-free health and melanoma recurrence (with or without IFN alpha-2b) leading to cancer death. We also asked patients the improvement in 5-year disease-free survival they would require to tolerate IFN. RESULTS Utilities for melanoma recurrence with or without IFN alpha-2b were significantly lower than utilities for all IFN alpha-2b toxicities but were not significantly different from each other. At least half of the patients were willing to tolerate mild-moderate and severe IFN alpha-2b toxicity for 4% and 10% improvements, respectively, in 5-year disease-free survival. CONCLUSION On average, patients rate quality of life with melanoma recurrence much lower than even severe IFN alpha-2b toxicity. These results suggest that recurrence-free survival is highly valued by patients. The utilities measured in our study can be applied directly to quality-of-life determinations in clinical trials of adjuvant IFN alpha-2b to measure the net benefit of therapy.

Implications of mobility impairment on the diagnosis and treatment of breast cancer.

BACKGROUND Among women with chronic, preexisting mobility impairments, we sought to explore how their mobility difficulties affected the diagnosis and treatment of early-stage breast cancer METHODS This is a qualitative analysis of transcripts from in-depth in-person or telephone interviews with 20 English-speaking women who had early-stage breast cancer, were <60 years of age, and had chronic difficulty walking or used wheeled mobility aids at the time of their breast cancer diagnoses RESULTS Nine women were disabled by polio as children or had postpolio syndrome, 3 had cerebral palsy, 3 had spinal cord injury, and 5 had other conditions. Most women reported difficulty obtaining mammograms, primarily because of inaccessible equipment, positioning problems, and difficulties with uncontrollable movements. Many women made decisions about surgical approach and chemotherapy by explicitly considering how various therapies would affect their arms, which are essential to their mobility (they use ambulation aids, self-propel manual wheelchairs, or otherwise rely on their arms for mobility or safety). Managing at home after surgery posed major mobility challenges, especially for women who lived alone. Several women reported feeling they suffered more chemotherapy side effects than do women without mobility problems. Weight gains with endocrine therapy compromised the mobility of several women. CONCLUSIONS Increasing numbers of American women are living with mobility disabilities and entering age ranges with increased risks of breast cancer. Mobility impairments can affect women at every point during early-stage breast cancer diagnosis, therapy, and recovery. Clinicians must consider womens mobility functioning in making therapeutic recommendations to women with impaired mobility who develop breast cancer.

Family interactions among African American prostate cancer survivors.

Prostate cancer affects African Americans at a higher rate than any other ethnic group in the United States. Prostate cancer does not only affect the man with the disease but also affects those individuals who are closest to him, such as his family and friends. Open communication is valuable in coping with stressors that are affiliated with chronic illnesses. This article focuses on family and friend social support of men with prostate cancer. Data analysis revealed that support from family members and friends plays an important role in how men cope with their treatment and recovery from prostate cancer.

Adrenocortical carcinoma and succinate dehydrogenase gene mutations: An observational case series

OBJECTIVE Germline loss-of-function mutations in succinate dehydrogenase (SDHx) genes results in rare tumor syndromes that include pheochromocytoma, paraganglioma, and others. Here we report a case series of patients with adrenocortical carcinoma (ACC) that harbor SDHx mutations. PATIENTS AND RESULTS We report four unrelated patients with ACC and SDHx mutations. All cases presented with Cushing syndrome and large adrenal masses that were confirmed to be ACC on pathology. All four ACC specimens were found to have truncating mutations in either SDHC or SDHA, while cases 1, 2 and 3 also had the mutations confirmed in the germline: Case 1: SDHC c.397C > T, pR133X; Case 2: SDHC c.43C > T, p.R15X; Case 3: SDHA c.91C > T, p.R31X; Case 4: SDHA c.1258C > T, p.Q420X. Notably, Case 1 had a father and daughter who both harbored the same SDHC germline mutation, and the father had a paraganglioma and renal cell carcinoma. A combination of next generation sequencing, and/or immunohistochemistry, and/or mass spectroscopy was used to determine whether there was loss of heterozygosity and/or loss of SDH protein expression or function within the ACC. Potential evidence of loss of heterozygosity was observed only in Case 2. CONCLUSIONS We observed truncating mutations in SDHA or SDHC in the ACC and/or germline of four unrelated patients. Given how statistically improbable the concurrence of ACC and pathogenic germline SDHx mutations is expected to be, these observations raise the question whether ACC may be a rare manifestation of SDHx mutation syndromes. Further studies are needed to investigate the possible role of SDH deficiency in ACC pathogenesis.

Quality-Adjusted Survival Analysis in Cancer Clinical Trials

The quality of life of patients is an important component for the evaluation of therapies in clinical trials, especially in cancer. The Quality-adjusted Time Without Symptoms and Toxicity (Q-TWiST) method evaluates treatment trade-offs in clinical trials using an endpoint based on both quantity and quality of life. The methodology has been most useful for evaluating the trade-off between increased toxic side effects of treatment and improved clinical outcome. This paper provides an overview of the Q-TWiST method, brief descriptions of related statistical tools for regression analysis and meta-analysis, and examples illustrating the techniques using data from cancer clinical trials.

Intravesical Therapy for Superficial Bladder Cancer

The bladder is an ideal organ for the application of regional chemotherapy. The urethra provides easy and relatively noninvasive access for the introduction of therapeutic agents, the urothelium provides a protective barrier that prevents the systemic absorption of the most commonly used intravesical agents, the intact ureterovesical junction prevents reflux of these agents into the upper urinary tracts, voluntary control of the external urinary sphincter allows a prolonged dwell time for maximal tumor contact, and the agents are discarded from the bladder during micturition, without the need for further instrumentation. The chief limitations of the regional approach for bladder cancer (BC) are that the depth of penetration of available agents is limited to a few millimeters, restricting use to those patients with superficial tumors; the production of urine during a prolonged dwell time may dilute the concentration of the agent, and therefore its therapeutic effect; variations in urine pH may effect the antitumor efficacy of some agents; and some agents produce a substantial local toxicity.