Lack of Patient-Clinician Concordance in Cancer Patients: Its Relation With Patient Variables.

CONTEXT: Patients with cancer are bothered by its diagnosis, treatment, and associated uncertainty. Lack of concordance (LOC) of patients' reporting of their symptoms and quality of life (QOL) with that of their clinicians has been observed in cancer care. However, information regarding the reporting of patients' bother due to aspects of cancer experience and their clinicians' assessment is lacking. OBJECTIVES: The objective was to describe cancer patients' bother due to aspects of their disease experience and explore the concordance (LOC) or a lack thereof between patients' and clinicians' reporting of patients' bother and factors associated with it. METHODS: Data from a prospective study of cancer patients' symptoms were analyzed. LOC was defined as any discrepancy between patient-clinician pairs in reporting patients' bother due to disease, cancer treatment, comorbidity, and side effects of symptom management. The relation of LOC to patients' QOL and distress was also explored. RESULTS: Of the 2597 patients analyzed, a perfect concordance was observed in 37%-42%. Clinicians underestimated the severity of bother in 62%-76% of discordant cases. LOC was significantly associated with patient-reported distress and poor QOL. Referral for symptom management was associated with the clinician's rating of patients' bother, and LOC was associated with likelihood of poor compliance with recommendations for symptom management. CONCLUSION: Majority of clinicians tended to underestimate cancer patients' bother, and this was associated with poor QOL of cancer patients and their distress. Future studies should examine the LOC and its correlates to confirm the results of this study.

Phase II Study of Gemcitabine, Carboplatin, and Iniparib As Neoadjuvant Therapy for Triple-Negative and BRCA1/2 Mutation-Associated Breast Cancer With Assessment of a Tumor-Based Measure of Genomic Instability: PrECOG 0105.

PURPOSE: This study was designed to assess efficacy, safety, and predictors of response to iniparib in combination with gemcitabine and carboplatin in early-stage triple-negative and BRCA1/2 mutation-associated breast cancer. PATIENTS AND METHODS: This single-arm phase II study enrolled patients with stage I to IIIA (T ≥ 1 cm) estrogen receptor-negative (≤ 5%), progesterone receptor-negative (≤ 5%), and human epidermal growth factor receptor 2-negative or BRCA1/2 mutation-associated breast cancer. Neoadjuvant gemcitabine (1,000 mg/m(2) intravenously [IV] on days 1 and 8), carboplatin (area under curve of 2 IV on days 1 and 8), and iniparib (5.6 mg/kg IV on days 1, 4, 8, and 11) were administered every 21 days for four cycles, until the protocol was amended to six cycles. The primary end point was pathologic complete response (no invasive carcinoma in breast or axilla). All patients underwent comprehensive BRCA1/2 genotyping, and homologous recombination deficiency was assessed by loss of heterozygosity (HRD-LOH) in pretreatment core breast biopsies. RESULTS: Among 80 patients, median age was 48 years; 19 patients (24%) had germline BRCA1 or BRCA2 mutations; clinical stage was I (13%), IIA (36%), IIB (36%), and IIIA (15%). Overall pathologic complete response rate in the intent-to-treat population (n = 80) was 36% (90% CI, 27 to 46). Mean HRD-LOH scores were higher in responders compared with nonresponders (P = .02) and remained significant when BRCA1/2 germline mutations carriers were excluded (P = .021). CONCLUSION: Preoperative combination of gemcitabine, carboplatin, and iniparib is active in the treatment of early-stage triple-negative and BRCA1/2 mutation-associated breast cancer. The HRD-LOH assay was able to identify patients with sporadic triple-negative breast cancer lacking a BRCA1/2 mutation, but with an elevated HRD-LOH score, who achieved a favorable pathologic response. Confirmatory controlled trials are warranted.

Comparison of performance of various tumour response criteria in assessment of regorafenib activity in advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib.

PURPOSE: To compare performance of various tumour response criteria (TRCs) in assessment of regorafenib activity in patients with advanced gastrointestinal stromal tumour (GIST) with prior failure of imatinib and sunitinib. METHODS: Twenty participants in a phase II trial received oral regorafenib (median duration 47 weeks; interquartile range (IQR) 24-88) with computed tomography (CT) imaging at baseline and every two months thereafter. Tumour response was prospectively determined on using Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, and retrospectively reassessed for comparison per RECIST 1.0, World Health Organization (WHO) and Choi criteria, using the same target lesions. Clinical benefit rate [CBR; complete or partial response (CR or PR) or stable disease (SD)≥16 weeks] and progression-free survival (PFS) were compared between various TRCs using kappa statistics. Performance of TRCs in predicting overall survival (OS) was compared by comparing OS in groups with progression-free intervals less than or greater than 20 weeks by each TRC using c-statistics. RESULTS: PR was more frequent by Choi (90%) than RECIST 1.1, RECIST 1.0 and WHO (20% each), however, CBR was similar between various TRCs (overall CBR 85-90%, 95-100% agreement between all TRC pairs). PFS per RECIST 1.0 was similar to RECIST 1.1 (median 44 weeks versus 58 weeks), and shorter for WHO (median 34 weeks) and Choi (median 24 weeks). With RECIST 1.1, RECIST 1.0 and WHO, there was moderate concordance between PFS and OS (c-statistics 0.596-0.679). Choi criteria had less favourable concordance (c-statistic 0.506). CONCLUSIONS: RECIST 1.1 and WHO performed somewhat better than Choi criteria as TRC for response evaluation in patients with advanced GIST after prior failure on imatinib and sunitinib.

Transoral resection of pharyngeal cancer: summary of a National Cancer Institute Head and Neck Cancer Steering Committee Clinical Trials Planning Meeting, November 6-7, 2011, Arlington, Virginia.

Recent advances now permit resection of many pharyngeal tumors through the open mouth, an approach that can greatly reduce the morbidity of surgical exposure. These transoral techniques are being rapidly adopted by the surgical community and hold considerable promise. On November 6-7, 2011, the National Cancer Institute sponsored a Clinical Trials Planning Meeting to address how to further investigate the use of transoral surgery, both in the good prognosis human papillomavirus (HPV)-initiated oropharyngeal cancers, and in those with HPV-unrelated disease. The proceedings of this meeting are summarized.

A phase II study of mifepristone (RU-486) in castration-resistant prostate cancer, with a correlative assessment of androgen-related hormones.

OBJECTIVE: To evaluate mifepristone (RU-486) in patients with castration-resistant prostate cancer (CRPC), with a correlative assessment of serum androgens and androgen metabolites PATIENTS AND METHODS: The androgen receptor (AR) is critical in the development and progression of prostate cancer, but available antiandrogens incompletely abrogate AR signalling. Mifepristone is a potent AR antagonist that functions by competing with androgen, preventing AR coactivator binding and by enhancing binding of AR corepressors. Patients with CRPC were treated with mifepristone 200 mg/day oral until disease progression. Testosterone, dihydrotestosterone (DHT), androstenedione, dihydroepiandrosterone sulphate and the testosterone metabolite 3 alpha-diol G, were measured at baseline and during therapy. RESULTS: Nineteen patients were enrolled between April and August 2005; they were treated for a median (range) of 85 (31-338) days. The median prostate-specific antigen (PSA) level at enrollment was 22.0 (3.0-937.2) ng/mL. No patient had a PSA response (>50% reduction in PSA). Six patients had stable disease for a median of 5.5 months. After 1 month, adrenal androgens were increased and testosterone and DHT increased by 91% and 80%, respectively, compared to baseline. CONCLUSION: Mifepristone had limited activity in patients with CRPC, and stimulated a marked increase in adrenal androgens, testosterone and DHT. We hypothesise that inhibition of glucocorticoid receptor by mifepristone resulted in an increase in adrenocorticotropic hormone and subsequent increase in adrenal androgens, and that their conversion by tumour cells to testosterone and DHT probably limited the efficacy of mifepristone. These data emphasize the continued importance of alternative androgen sources in AR signalling in CRPC.

Bringing prostate cancer quality of life research back to the bedside: translating numbers into a format that patients can understand.

PURPOSE: Although measuring quality of life of patients with prostate cancer serves important research goals, its primary clinical purpose is informing patients. Sophisticated quality of life measures produce purely numerical results that patients have difficulty understanding. We present an approach that preserves the methodological strengths of validated multi-item measures but provides more accessible information for clinical use. MATERIALS AND METHODS: Using validated indexes measuring urinary, bowel and sexual function we surveyed patients with clinically localized prostate cancer before treatment and at intervals thereafter. Based on patient responses to parallel distress measures we defined 3 levels of function, including normal-no abnormal symptom, intermediate-any abnormal symptom but none severely abnormal and poor-any severely abnormal symptom. We then translated patient survey results into these levels. To assess measurement properties we compared average symptom distress scores in patients at each symptom level. RESULTS: Levels of function and patient distress scores correlated strongly. Large and approximately equal differences in distress scores separated patients at successive levels in all symptom indexes (effect size greater than 1.2, p < 0.0001). Using these categories we created tables showing 24-month outcomes in 417 previously reported patients by pretreatment symptom level and treatment, providing a tool for patients to determine posttreatment outcomes in similar patients. CONCLUSIONS: Using symptom indexes to define levels of function produces a quality of life metric that is valid, defines quantitative intervals, is transparent and may be more useful to patients. This approach provides methodologically sound outcome information to patients attempting to choose a prostate cancer treatment.

Assessing a prostate cancer brachytherapy technique using early patient-reported symptoms: a potential early indicator for technology assessment?

Brachytherapy for early prostate cancer can cause long-term urinary, bowel, and sexual dysfunction. Modifying technique may mitigate complications, but definitive outcome assessment requires long-term follow-up. Although radiation dose plausibly mediates all treatment-related toxicity, short-term symptoms may indicate long-term outcomes. We sought an early indication of whether a modified brachytherapy technique successfully decreased toxicity in the anticipated direction by assessing changes in symptoms and symptom distress 3 months after treatment. In a prospective study of clinically localized prostate cancer using a validated, patient-reported questionnaire, we assessed 85 men, whose primary treatment was brachytherapy alone, prior to treatment and 3 months after the procedure. Twenty-two men received standard ultrasound-guided brachytherapy (SB), and 63 men received magnetic resonance imaging-guided brachytherapy (MB), a technique intended to decrease urinary toxicity by reducing urethral irradiation. Patient age and other sociodemographic variables were similar in the 2 groups. The MB group experienced a greater increase in urinary obstruction/irritation symptoms (P = 0.02) and sexual function distress, but not sexual dysfunction (P = 0.22), whereas the SB group reported a smaller increase in bowel symptoms (P = 0.04) and bowel distress (P = 0.02). We found reduced short-term urinary obstruction/irritation and increased bowel problems after MB consistent with the hypothesized effects of the modified technique, although no obvious mechanism explains the decreased sexual function distress in MB patients. Whether these short-term changes predict long-term outcome differences will require much longer follow-up. However, these results suggest that measuring early symptoms may indicate whether an altered brachytherapy treatment technique has intended favorable consequences, potentially accelerating technology assessment.