Relative survival is an adequate estimate of cancer-specific survival: baseline mortality-adjusted 10-year survival of 771 rectal cancer patients.

BACKGROUND The objective of the present investigation is to assess the baseline mortality-adjusted 10-year survival of rectal cancer patients. METHODS Ten-year survival was analyzed in 771 consecutive American Joint Committee on Cancer (AJCC) stage I-IV rectal cancer patients undergoing open resection between 1991 and 2008 using risk-adjusted Cox proportional hazard regression models adjusting for population-based baseline mortality. RESULTS The median follow-up of patients alive was 8.8 years. The 10-year relative, overall, and cancer-specific survival were 66.5% [95% confidence interval (CI) 61.3-72.1], 48.7% (95% CI 44.9-52.8), and 66.4% (95% CI 62.5-70.5), respectively. In the entire patient sample (stage I-IV) 47.3% and in patients with stage I-III 33.6 % of all deaths were related to rectal cancer during the 10-year period. For patients with AJCC stage I rectal cancer, the 10-year overall survival was 96% and did not significantly differ from an average population after matching for gender, age, and calendar year (p = 0.151). For the more advanced tumor stages, however, survival was significantly impaired (p < 0.001). CONCLUSIONS Retrospective investigations of survival after rectal cancer resection should adjust for baseline mortality because a large fraction of deaths is not cancer related. Stage I rectal cancer patients, compared to patients with more advanced disease stages, have a relative survival close to 100% and can thus be considered cured. Using this relative-survival approach, the real public health burden caused by rectal cancer can reliably be analyzed and reported.

Differences in Time to Disease Progression Do Not Predict for Cancer-specific Survival in Patients Receiving Immediate or Deferred Androgen-deprivation Therapy for Prostate Cancer: Final Results of EORTC Randomized Trial 30891 with 12 Years of Follow-up

BACKGROUND Trials assessing the benefit of immediate androgen-deprivation therapy (ADT) for treating prostate cancer (PCa) have often done so based on differences in detectable prostate-specific antigen (PSA) relapse or metastatic disease rates at a specific time after randomization. OBJECTIVE Based on the long-term results of European Organization for Research and Treatment of Cancer (EORTC) trial 30891, we questioned if differences in time to progression predict for survival differences. DESIGN, SETTING, AND PARTICIPANTS EORTC trial 30891 compared immediate ADT (n=492) with orchiectomy or luteinizing hormone-releasing hormone analog with deferred ADT (n=493) initiated upon symptomatic disease progression or life-threatening complications in randomly assigned T0-4 N0-2 M0 PCa patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Time to first objective progression (documented metastases, ureteric obstruction, not PSA rise) and time to objective castration-resistant progressive disease were compared as well as PCa mortality and overall survival. RESULTS AND LIMITATIONS After a median of 12.8 yr, 769 of the 985 patients had died (78%), 269 of PCa (27%). For patients receiving deferred ADT, the overall treatment time was 31% of that for patients on immediate ADT. Deferred ADT was significantly worse than immediate ADT for time to first objective disease progression (p<0.0001; 10-yr progression rates 42% vs 30%). However, time to objective castration-resistant disease after deferred ADT did not differ significantly (p=0.42) from that after immediate ADT. In addition, PCa mortality did not differ significantly, except in patients with aggressive PCa resulting in death within 3-5 yr after diagnosis. Deferred ADT was inferior to immediate ADT in terms of overall survival (hazard ratio: 1.21; 95% confidence interval, 1.05-1.39; p [noninferiority]=0.72, p [difference] = 0.0085). CONCLUSIONS This study shows that if hormonal manipulation is used at different times during the disease course, differences in time to first disease progression cannot predict differences in disease-specific survival. A deferred ADT policy may substantially reduce the time on treatment, but it is not suitable for patients with rapidly progressing disease.

Combination of expression levels of miR-21 and miR-126 is associated with cancer-specific survival in clear-cell renal cell carcinoma

BACKGROUND Renal cell carcinoma (RCC) is marked by high mortality rate. To date, no robust risk stratification by clinical or molecular prognosticators of cancer-specific survival (CSS) has been established for early stages. Transcriptional profiling of small non-coding RNA gene products (miRNAs) seems promising for prognostic stratification. The expression of miR-21 and miR-126 was analysed in a large cohort of RCC patients; a combined risk score (CRS)-model was constructed based on expression levels of both miRNAs. METHODS Expression of miR-21 and miR-126 was evaluated by qRT-PCR in tumour and adjacent non-neoplastic tissue in n = 139 clear cell RCC patients. Relation of miR-21 and miR-126 expression with various clinical parameters was assessed. Parameters were analysed by uni- and multivariate COX regression. A factor derived from the z-score resulting from the COX model was determined for both miRs separately and a combined risk score (CRS) was calculated multiplying the relative expression of miR-21 and miR-126 by this factor. The best fitting COX model was selected by relative goodness-of-fit with the Akaike information criterion (AIC). RESULTS RCC with and without miR-21 up- and miR-126 downregulation differed significantly in synchronous metastatic status and CSS. Upregulation of miR-21 and downregulation of miR-126 were independently prognostic. A combined risk score (CRS) based on the expression of both miRs showed high sensitivity and specificity in predicting CSS and prediction was independent from any other clinico-pathological parameter. Association of CRS with CSS was successfully validated in a testing cohort containing patients with high and low risk for progressive disease. CONCLUSIONS A combined expression level of miR-21 and miR-126 accurately predicted CSS in two independent RCC cohorts and seems feasible for clinical application in assessing prognosis.

Sharing decisions in breast cancer care: Development of the Decision Analysis System for Oncology (DAS-O) to identify shared decision making during treatment consultations

Shared Decision Making (SDM) is widely accepted as the preferred method for reaching treatment decisions in the oncology setting including those about clinical trial participation: however, there is some disagreement between researchers over the components of SDM. Specific standardized coding systems are needed to help overcome this difficulty.

Prognostic value of microvascular invasion in predicting the cancer specific survival and risk of metastatic disease in renal cell carcinoma: a multicenter investigation

While microvascular invasion is an accepted risk factor in various cancers, its prognostic role in renal cell carcinoma is still unclear. Therefore, a large multicenter study examining the experience of 5 international institutions was performed to evaluate the prognostic value of microvascular invasion in the occurrence of metastases and cancer specific survival.

Smoking negatively impacts renal cell carcinoma overall and cancer-specific survival

Tobacco use is a leading cause of premature death, yet few studies have investigated the effect of tobacco exposure on the outcome of patients with renal cell carcinoma (RCC). The authors of this report retrospectively studied the impact of smoking on clinicopathologic factors, survival outcomes, and p53 expression status in a large cohort of patients with RCC.

Meeting the decision-making preferences of patients with breast cancer in oncology consultations: impact on decision-related outcomes

To investigate how involvement preferences of patients with breast cancer change during the treatment decision-making process and determine the impact of meeting patients' expectations on decision-making outcomes.

The SAKK cancer-specific geriatric assessment (C-SGA): a pilot study of a brief tool for clinical decision-making in older cancer patients

BACKGROUND Recommendations from international task forces on geriatric assessment emphasize the need for research including validation of cancer-specific geriatric assessment (C-SGA) tools in oncological settings. The objective of this study was to evaluate the feasibility of the SAKK Cancer-Specific Geriatric Assessment (C-SGA) in clinical practice. METHODS A cross sectional study of cancer patients >=65 years old (N = 51) with pathologically confirmed cancer presenting for initiation of chemotherapy treatment (07/01/2009-03/31/2011) at two oncology departments in Swiss canton hospitals: Kantonsspital Graubunden (KSGR N = 25), Kantonsspital St. Gallen (KSSG N = 26). Data was collected using three instruments, the SAKK C-SGA plus physician and patient evaluation forms. The SAKK C-SGA includes six measures covering five geriatric assessment domains (comorbidity, function, psychosocial, nutrition, cognition) using a mix of medical record abstraction (MRA) and patient interview. Five individual domains and one overall SAKK C-SGA score were calculated and dichotomized as below/above literature-based cut-offs. The SAKK C-SGA was evaluated by: patient and physician estimated time to complete, ease of completing, and difficult or unanswered questions. RESULTS Time to complete the patient questionnaire was considered acceptable by almost all (>=96%) patients and physicians. Patients reported slightly shorter times to complete the questionnaire than physicians (17.33 +/- 7.34 vs. 20.59 +/- 6.53 minutes, p = 0.02). Both groups rated the patient questionnaire as easy/fairly easy to complete (91% vs. 84% respectively, p = 0.14) with few difficult or unanswered questions. The MRA took on average 8.32 +/- 4.72 minutes to complete. Physicians (100%) considered time to complete MRA acceptable, 96% rated it as easy/fairly easy to complete. Individual study site populations differed on health-related characteristics (excellent/good physician-rated general health KSGR 71% vs. KSSG 32%, p = 0.007). The overall mean C-SGA score was 2.4 +/- 1.12. Patients at KSGR had lower C-SGA scores (2.00 +/- 1.19 vs. 2.81 +/- 0.90, p = 0.009) and a smaller proportion (28% vs.65%, p = 0.008) was above the C-SGA cut-off score compared to KSSG. CONCLUSIONS These results suggest the SAKK C-SGA is a feasible practical tool for use in clinical practice. It demonstrated discriminative ability based on objective geriatric assessment measures, but additional investigations on use for clinical decision-making are warranted. The SAKK C-SGA also provides important usable domain information for intervention to optimize outcomes in older cancer patients.

Sugar concentration influences decision making in <i>Apis mellifera</i> L. workers during early-stage honey storage behaviour

Decision making in honeybees is based on in- formation which is acquired and processed in order to make choices between two or more al- ternatives. These choices lead to the expression of optimal behaviour strategies such as floral constancy. Optimal foraging strategies such as floral constancy improve a colony’s chances of survival, however to our knowledge, there has been no research on decision making based on optimal storage strategies. Here we show, using diagnostic radioentomology, that decision mak- ing in storer bees is influenced by nectar sugar concentrations and that, within 48 hours of col- lection, honeybees workers store carbohydrates in groups of cells with similar sugar concentra- tions in a nonrandom way. This behaviour, as evidenced by patchy spatial cell distributions, would help to hasten the ripening process by reducing the distance between cells of similar sugar concentrations. Thus, colonies which ex- hibit optimal storage strategies such as these would have an evolutionary advantage and im- prove colony survival expectations over less efficient colonies and it should be plausible to select colonies that exhibit these preferred traits.

Predictors of satisfaction with treatment decision, decision-making preferences, and main treatment goals in patients with advanced cancer

Purpose This study investigated satisfaction with treatment decision (SWTD), decision-making preferences (DMP), and main treatment goals, as well as evaluated factors that predict SWTD, in patients receiving palliative cancer treatment at a Swiss oncology network. Patients and methods Patients receiving a new line of palliative treatment completed a questionnaire 4–6 weeks after the treatment decision. Patient questionnaires were used to collect data on sociodemographics, SWTD (primary outcome measure), main treatment goal, DMP, health locus of control (HLoC), and several quality of life (QoL) domains. Predictors of SWTD (6 = worst; 30 = best) were evaluated by uni- and multivariate regression models. Results Of 480 participating patients in eight hospitals and two private practices, 445 completed all questions regarding the primary outcome measure. Forty-five percent of patients preferred shared, while 44 % preferred doctor-directed, decision-making. Median duration of consultation was 30 (range: 10–200) minutes. Overall, 73 % of patients reported high SWTD (≥24 points). In the univariate analyses, global and physical QoL, performance status, treatment goal, HLoC, prognosis, and duration of consultation were significant predictors of SWTD. In the multivariate analysis, the only significant predictor of SWTD was duration of consultation (p = 0.01). Most patients indicated hope for improvement (46 %), followed by hope for longer life (26 %) and better quality of life (23 %), as their main treatment goal. Conclusion Our results indicate that high SWTD can be achieved in most patients with a 30-min consultation. Determining the patient’s main treatment goal and DMP adds important information that should be considered before discussing a new line of palliative treatment.

Impact of synchronous metastasis distribution on cancer specific survival in renal cell carcinoma after radical nephrectomy with tumor thrombectomy

PURPOSE Metastatic renal cell carcinoma can be clinically diverse in terms of the pattern of metastatic disease and response to treatment. We studied the impact of metastasis and location on cancer specific survival. MATERIALS AND METHODS The records of 2,017 patients with renal cell cancer and tumor thrombus who underwent radical nephrectomy and tumor thrombectomy from 1971 to 2012 at 22 centers in the United States and Europe were analyzed. Number and location of synchronous metastases were compared with respect to patient cancer specific survival. Multivariable Cox regression models were used to quantify the impact of covariates. RESULTS Lymph node metastasis (155) or distant metastasis (725) was present in 880 (44%) patients. Of the patients with distant disease 385 (53%) had an isolated metastasis. The 5-year cancer specific survival was 51.3% (95% CI 48.6-53.9) for the entire group. On univariable analysis patients with isolated lymph node metastasis had a significantly worse cancer specific survival than those with a solitary distant metastasis. The location of distant metastasis did not have any significant effect on cancer specific survival. On multivariable analysis the presence of lymph node metastasis, isolated distant metastasis and multiple distant metastases were independently associated with cancer specific survival. Moreover higher tumor thrombus level, papillary histology and the use of postoperative systemic therapy were independently associated with worse cancer specific survival. CONCLUSIONS In our multi-institutional series of patients with renal cell cancer who underwent radical nephrectomy and tumor thrombectomy, almost half of the patients had synchronous lymph node or distant organ metastasis. Survival was superior in patients with solitary distant metastasis compared to isolated lymph node disease.

Impact of histologic subtype on cancer-specific survival in patients with renal cell carcinoma and tumor thrombus

BACKGROUND Although different prognostic factors for patients with renal cell carcinoma (RCC) and vena cava tumor thrombus (TT) have been studied, the prognostic value of histologic subtype in these patients remains unclear. OBJECTIVE We analyzed the impact of histologic subtype on cancer-specific survival (CSS). DESIGN, SETTINGS, AND PARTICIPANTS We retrospectively analyzed the records of 1774 patients with RCC and TT who underwent radical nephrectomy and tumor thrombectomy from 1971 to 2012 at 22 US and European centers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Multivariable ordered logistic and Cox regression models were used to quantify the impact of tumor histology on CSS. RESULTS AND LIMITATIONS Overall 5-yr CSS was 53.4% (confidence interval [CI], 50.5-56.2) in the entire group. TT level (according to the Mayo classification of macroscopic venous invasion in RCC) was I in 38.5% of patients, II in 30.6%, III in 17.3%, and IV in 13.5%. Histologic subtypes were clear cell renal cell carcinoma (cRCC) in 89.9% of patients, papillary renal cell carcinoma (pRCC) in 8.5%, and chromophobe RCC in 1.6%. In univariable analysis, pRCC was associated with a significantly worse CSS (p<0.001) compared with cRCC. In multivariable analysis, the presence of pRCC was independently associated with CSS (hazard ratio: 1.62; CI, 1.01-2.61; p<0.05). Higher TT level, positive lymph node status, distant metastasis, and fat invasion were also independently associated with CSS. CONCLUSIONS In our multi-institutional series, we found that patients with pRCC and vena cava TT who underwent radical nephrectomy and tumor thrombectomy had significantly worse cancer-specific outcomes when compared with patients with other histologic subtypes of RCC. We confirmed that higher TT level and fat invasion were independently associated with reduced CSS.

How do sport clubs recruit volunteers? Analyzing and developing a typology of decision-making processes on recruiting volunteers in sport clubs.

Effective strategies for recruiting volunteers who are prepared to make a long-term commitment to formal positions are essential for the survival of voluntary sport clubs. This article examines the decision-making processes in relation to these efforts. Under the assumption of bounded rationality, the garbage can model is used to grasp these decision-making processes theoretically and access them empirically. Based on case study framework an in-depth analysis of recruitment practices was conducted in nine selected sport clubs. Results showed that the decision-making processes are generally characterized by a reactive approach in which dominant actors try to handle personnel problems of recruitment in the administration and sport domains through routine formal committee work and informal networks. In addition, it proved possible to develop a typology that deliver an overview of different decision-making practices in terms of the specific interplay of the relevant components of process control (top-down vs. bottom-up) and problem processing (situational vs. systematic).

Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial

BACKGROUND Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone. METHODS Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m(2)) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544). FINDINGS 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60-71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6%) men were previously treated with local therapy, and median prostate-specific antigen was 65 ng/mL (IQR 23-184). Median follow-up was 43 months (IQR 30-60). There were 415 deaths in the control group (347 [84%] prostate cancer). Median overall survival was 71 months (IQR 32 to not reached) for SOC-only, not reached (32 to not reached) for SOC + ZA (HR 0·94, 95% CI 0·79-1·11; p=0·450), 81 months (41 to not reached) for SOC + Doc (0·78, 0·66-0·93; p=0·006), and 76 months (39 to not reached) for SOC + ZA + Doc (0·82, 0·69-0·97; p=0·022). There was no evidence of heterogeneity in treatment effect (for any of the treatments) across prespecified subsets. Grade 3-5 adverse events were reported for 399 (32%) patients receiving SOC, 197 (32%) receiving SOC + ZA, 288 (52%) receiving SOC + Doc, and 269 (52%) receiving SOC + ZA + Doc. INTERPRETATION Zoledronic acid showed no evidence of survival improvement and should not be part of standard of care for this population. Docetaxel chemotherapy, given at the time of long-term hormone therapy initiation, showed evidence of improved survival accompanied by an increase in adverse events. Docetaxel treatment should become part of standard of care for adequately fit men commencing long-term hormone therapy. FUNDING Cancer Research UK, Medical Research Council, Novartis, Sanofi-Aventis, Pfizer, Janssen, Astellas, NIHR Clinical Research Network, Swiss Group for Clinical Cancer Research.

Contrast-enhanced 3-D MRA in decision making for carotid endarterectomy: a 6-year experience

BACKGROUND: Systematic need for angiography in diagnosis of carotid artery stenosis and indication of surgical therapy is still debated. Noninvasive imaging techniques such as MR angiography (MRA) or CT angiography (CTA) offer an alternative to digital subtraction angiography (DSA) and are increasingly used in clinical practice. In this study, we present the radiological characteristics and clinical results of a series of patients operated on the basis of combined ultrasonography (US)/MRA. METHODS: This observational study included all the patients consecutively operated for a carotid stenosis in our Department from October 1998 to December 2004. The applied MRA protocol had previously been established in a large correlation study with DSA. DSA was used only in case of discordance between US and MRA. The preoperative radiological information furnished by MRA was compared with intraoperative findings. The outcome of the operation was assessed according to ECST criteria. RESULTS: Among 327 patients, preoperative MRA was performed in 278 (85%), DSA in 44 (13.5%) and CT angiography in 5 (1.5%). Most of DSA studies were performed as emergency for preparation of endovascular therapy or for reasons other than carotid stenosis. Eleven additional DSA (3.3%) complemented US/MRA, mostly because diverging diagnosis of subocclusion of ICA. No direct morbidity or intraoperative difficulty was related to preoperative MRA. Combined mortality/major morbidity rate was 0.9% (3 patients) and minor morbidity rate 5.5% (18 patients). CONCLUSIONS: This observational study describes a well-established practice of carotid surgery and supports the exclusive use of non invasive diagnostic imaging for indicating and deciding the operation.