Multi-parametric magnetic resonance imaging assessment of whole tumour heterogeneity for chemoradiotherapy response prediction in rectal cancer.

BACKGROUND AND PURPOSE: Prediction of chemoradiotherapy response (CRT) in locally advanced rectal cancer would enable stratification of management. The purpose was to prospectively evaluate multi-parametric magnetic resonance imaging (MRI) assessment of tumour heterogeneity combining diffusion weighted imaging (DWI) and dynamic contrast enhanced (DCE) MRI for the prediction of CRT response in locally advanced rectal cancer. MATERIALS AND METHODS: Patients with Stage II or III rectal adenocarcinoma undergoing neoadjuvant CRT and surgery underwent MRI (DWI and DCE) before, during (week 3), and after CRT (1 week before surgery). Patients with histopathology tumour regression grade (TRG) 0-1 were classified as responders, and TRG 2-3 were classified as non-responders. A whole tumour voxel-wise technique was used to produce apparent diffusion coefficient (ADC) and Ktrans (Tofts model) histograms derived from DWI and DCE-MRI, respectively. Logistic regression was used to predict response status for ADC and Ktrans quantiles. RESULTS: Thirty-three patients were included in this analysis; 16 responders, and 17 non-responders. On heterogeneity analysis, odds of being a responder were significantly higher after CRT (before surgery) for higher ADC 75th (p = 0.049) and ADC 90th (p = 0.034) percentile values. The Ktrans quantiles were lower in non-responders than responders before and during CRT, and higher after CRT although no significant association with response status was observed (p ≥ 0.10). CONCLUSIONS: DWI-MRI after CRT (before surgery) incorporating a histogram analysis of whole tumour heterogeneity was predictive of CRT response in patients with locally advanced rectal cancer. DCE-MRI did not add value in response prediction. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) number ACTRN12616001690448.

When do patient reported quality of life indicators become prognostic in breast cancer?

BACKGROUND: Various patient reported quality-of-life indicators are independently prognostic for survival in metastatic breast cancer and other cancers. The same measures recorded at first diagnosis of early breast cancer carry no corresponding prognostic information. The present study aims to assess at what time in the disease evolution the prognostic association appears. METHODS: Among 8024 patients enrolled in one of seven randomized controlled trials in early-stage breast cancer 3247 had a breast cancer relapse after a median follow-up of 12.1 years. Of these 677 had completed QL indicator assessments within defined windows 1, 2 or 3 months prior to relapse. We performed Cox regression analyses using these assessments and using identical instruments after relapse. All analyses were stratified by trial and adjusted for baseline clinicopathologic factors. RESULTS: QL indicators in the months before relapse were not significantly prognostic for subsequent survival with the possibly chance exception of mood at the second month before relapse. After relapse, physical well-being was statistically significantly associated with survival (P < 0.001). This prognostic significance increased in later post-relapse assessments. Similar findings were observed using patient-reported indicators for nausea and vomiting, appetite, coping effort, and health perception. CONCLUSIONS: Before cancer relapse, QL indicators were not generally prognostic for subsequent survival. After relapse, QL indicators substantially predicted OS, with a stronger association later in the course of relapsed disease. Simple patient perception of disease burden seems unlikely to explain this sudden change: rather the patient's awareness of disease relapse must contribute.

Patients' preferred and perceived roles in making decisions about adjuvant chemotherapy for non-small-cell lung cancer.

BACKGROUND: People with cancer have varying preferences for involvement in decision-making between active, collaborative and passive roles. We sought the preferred and perceived involvement in decision-making among patients considering adjuvant chemotherapy (ACT) after resection of early non-small cell lung cancer (NSCLC). METHODS: Patients considering ACT for NSCLC were asked to complete a self-administered questionnaire at baseline and 6 months. Preferred and perceived decision-making roles were assessed by the Control Preferences Scale (CPS). We examined differences between preferred and perceived roles, differences in preferred roles over time, determinants of preferences, and differences in treatment preferences between patients preferring active and less active roles. RESULTS: 98 patients completed the baseline questionnaire; 75 completed the 6 month questionnaire. Most patients were male (55%) with a median age of 64 years (range, 43-79 years). Preferred role in decision-making at baseline (n=98) was active in 27%, collaborative in 47%, and passive in 27%. Perceived decision-making roles matched the preferred role in 79% of patients. Individuals' role preferences often varied between baseline and 6 months, but there was no consistent direction to the change (25% changed preference to more active involvement, 22% to less active). Preferring a more active role was associated with university education (OR 2.9, p=0.02), deciding not to have ACT (OR 5.0, p<0.01), and worse health-related quality of life (HRQL) during ACT: physical well-being (OR 4.4, p=0.05), overall well-being (OR 5.5, p=0.02), sleep (OR 8.4, p<0.01) and shortness of breath (OR 7.6, p=0.01). Patients who preferred an active decision-making role judged larger survival benefits necessary to make ACT worthwhile than those preferring a passive role. CONCLUSION: Most patients with resected NSCLC preferred and perceived a collaborative role in decision-making about ACT. Clinicians should elicit and consider patients' preferences for involvement in decision-making when discussing ACT for NSCLC.

Patients' and doctors' preferences for adjuvant chemotherapy in resected non-small-cell lung cancer: What makes it worthwhile?

BACKGROUND: Adjuvant chemotherapy (ACT) in non-small-cell lung cancer (NSCLC) improves overall survival, but the benefits must be weighed against its harms. We sought to determine the survival benefits that patients and their doctors judged sufficient to make ACT in NSCLC worthwhile. METHODS: 122 patients completed a self-administered questionnaire at baseline and 6 months (before & after ACT, if they had it); 82 doctors completed the questionnaire once only. The time trade-off method was used to determine the minimum survival benefits judged sufficient in four hypothetical scenarios. Baseline survival times were 3 years & 5 years and baseline survival rates (at 5 years) were 50% & 65%. RESULTS: At baseline, the median benefits judged sufficient by patients were an extra 9 months (Interquartile range (IQR) 1-12 months) beyond 3 years & 5 years and an extra 5% (IQR 0.1-10%) beyond 50% & 65%. At 6 months (n=91), patients' preferences had the same median benefit (9 months & 5%) but varied more (IQRs 0-18 months & 0-15%) than at baseline. Factors associated with judging smaller benefits sufficient were deciding to have ACT (P=0.01, 0.02) and better well-being (P=0.01, 0.006) during ACT. Doctors' preferences, compared with patients' preferences, had similar median benefits (9 months & 5%) but varied less (IQR 6-12 months versus 1-12 months, P<0.001; 5%-10% versus 0.1-10%, P<0.001). CONCLUSION: Most patients and doctors judged moderate survival benefits sufficient to make ACT in NSCLC worthwhile, but the preferences of doctors varied less than those of patients. Doctors should endeavour to elicit patients' preferences during discussions about ACT in NSCLC.

Adjuvant chemotherapy for early colon cancer: what survival benefits make it worthwhile?

BACKGROUND: We sought to determine the minimum survival benefits that patients judged sufficient to make adjuvant chemotherapy for early colon cancer worthwhile, factors associated with these judgments; and, to compare a self-administered questionnaire with a validated, scripted interview. PATIENTS AND METHODS: One twenty three subjects who completed adjuvant chemotherapy for early colon cancer 3-60 months earlier completed a questionnaire; 97 were randomised to complete an interview before or after the questionnaire. Preferences were elicited by the time trade-off method in 4 hypothetical scenarios. Concordance between the interview and questionnaire was assessed with the intraclass correlation coefficient (ICC). RESULTS: Median age was 65 years (range 19-86), 52% were female and 74% had involved lymph nodes. Over 60% of patients judged an additional 1 month beyond life expectancies of 5 years or 15 years, and an additional 1-2% beyond 5-year survival rates of 85% or 65%, sufficient to make chemotherapy worthwhile. Subjects with tertiary education (p=0.003) or aged 75 years or less (p=0.02) judged larger benefits necessary to make chemotherapy worthwhile. Concordance between the interview and questionnaire was high (ICCs 0.71-0.82). CONCLUSIONS: Most subjects judged small survival benefits sufficient to make adjuvant chemotherapy worthwhile. A self-administered questionnaire was a valid and acceptable way of eliciting preferences.

A systematic review of physicians' survival predictions in terminally ill cancer patients.

OBJECTIVE: To systematically review the accuracy of physicians' clinical predictions of survival in terminally ill cancer patients. DATA SOURCES: Cochrane Library, Medline (1996-2000), Embase, Current Contents, and Cancerlit databases as well as hand searching. STUDY SELECTION: Studies were included if a physician's temporal clinical prediction of survival (CPS) and the actual survival (AS) for terminally ill cancer patients were available for statistical analysis. Study quality was assessed by using a critical appraisal tool produced by the local health authority. DATA SYNTHESIS: Raw data were pooled and analysed with regression and other multivariate techniques. RESULTS: 17 published studies were identified; 12 met the inclusion criteria, and 8 were evaluable, providing 1563 individual prediction-survival dyads. CPS was generally overoptimistic (median CPS 42 days, median AS 29 days); it was correct to within one week in 25% of cases and overestimated survival by at least four weeks in 27%. The longer the CPS the greater the variability in AS. Although agreement between CPS and AS was poor (weighted kappa 0.36), the two were highly significantly associated after log transformation (Spearman rank correlation 0.60, P < 0.001). Consideration of performance status, symptoms, and use of steroids improved the accuracy of the CPS, although the additional value was small. Heterogeneity of the studies' results precluded a comprehensive meta-analysis. CONCLUSIONS: Although clinicians consistently overestimate survival, their predictions are highly correlated with actual survival; the predictions have discriminatory ability even if they are miscalibrated. Clinicians caring for patients with terminal cancer need to be aware of their tendency to overestimate survival, as it may affect patients' prospects for achieving a good death. Accurate prognostication models incorporating clinical prediction of survival are needed.