Lower Risk Of Disease Recurrence Research Articles

Dose-response Effects of Aerobic Exercise Among Colon Cancer Survivors: A Randomized Phase II Trial

BackgroundObservational studies suggest that higher volumes of physical activity are associated with a lower risk of disease recurrence among survivors of colon cancer. However, the feasibility and safety of prescribing higher volumes of physical activity to survivors of colon cancer are unknown. Furthermore, the pathways through which exercise may reduce disease recurrence are unknown. Patients and MethodsSurvivors of stage I to III colon cancer were randomized to usual-care control, 150 minutes per week of aerobic exercise (low-dose), or 300 minutes per week of aerobic exercise (high-dose). Changes in soluble intercellular adhesion molecule-1 and vascular adhesion molecule-1 prognostic biomarkers were examined. ResultsFrom January 2015 to February 2016, 39 patients were enrolled (n = 13 usual-care control; n = 14 low-dose; n = 12 high-dose), and 38 participants completed the study (97% follow-up). Over 6 months, the low-dose group completed 142 minutes per week (92.8% adherence), and the high-dose group completed 247 minutes per week (89.0% adherence) of exercise. Compared with the control group, changes in soluble intercellular adhesion molecule-1 were −134.9 ng/mL (95% confidence interval, −238.1 to −31.6 ng/mL) in the low-dose group and −114.8 ng/mL (95% confidence interval, −222.5 to −7.1 ng/mL) in the high-dose group (linear Ptrend = .023; nonlinear Ptrend = .044). No changes were observed for soluable vascular adhesion molecule-1 (linear Ptrend = .791; nonlinear Ptrend = .604). Non-serious adverse events occurred at similar rates among randomized groups. No serious adverse events occurred. ConclusionHigher volumes of moderate-intensity aerobic exercise, up to 300 minutes per week, are feasible, safe, and elicit favorable changes in prognostic biomarkers among patients recently treated for stage I to III colon cancer. These data can be used to guide clinical recommendations for patients, and inform future trials.

The role of stem cell transplant for lymphoma in 2017.

The role of stem cell transplant for lymphoma in 2017.

Association between miRNA-binding site polymorphisms in double-strand break repair genes and risk of recurrence in patients with squamous cell carcinomas of the non-oropharynx.

Genetic polymorphisms at miRNA-binding sites may affect miRNA-mediated gene regulation. Thus, miRNA-binding site polymorphisms in double-strand break (DSB) repair genes may affect DNA repair capacity, which in turn could affect cancer prognosis. To determine whether miRNA-binding site polymorphisms in DSB repair genes are associated with the risk of recurrence of squamous cell carcinoma of the non-oropharynx (SCCNOP), we used a log-rank test and multivariable Cox models to evaluate the associations between miRNA-binding site polymorphisms in DSB repair genes and SCCNOP recurrence. Compared with patients without common homozygous genotypes, patients with the variant genotypes of ATM rs227091, LIG3 rs4796030, and RAD51 rs7180135 had significantly better disease-free survival (DFS) (log-rank P = 0.046, 0.002, and 0.041, respectively) and lower risk of disease recurrence [HR (95% CI) = 0.7 (0.6-0.9), 0.6 (0.5-0.9), and 0.7 (0.6-0.9), respectively]. Furthermore, patients with the variant genotypes of these 3 polymorphisms had significantly lower recurrence risk than those without common homozygous genotypes did [HR = 0.3 (95% CI = 0.2-0.7)]. Among patients who received chemoradiation, those with the individual or combined variant genotypes of the three polymorphisms had a significantly lower risk of disease recurrence than those with the individual or combined common homozygous genotypes did. The individual or combined variant genotypes of the ATM rs227091, LIG3 rs4796030, and RAD51 rs7180135 polymorphisms significantly modify the risk of SCCNOP recurrence, particularly for patients treated with chemoradiation. Future prospective studies with larger sample sizes are warranted to validate these findings to enable more effective personalized treatment for SCCNOP patients.

Prognostic value of androgen receptor in triple negative breast cancer: A meta-analysis.

BackgroundAndrogen receptor (AR) is a promising therapeutic target for breast cancer. However, its prognostic value remains controversial in triple negative breast cancer (TNBC). Here we present a meta-analysis to investigate the correlation between AR expression and TNBC prognosis.ResultsThirteen relevant studies with 2826 TNBC patients were included. AR positive rate was 24.4%. AR+ patients tended to have lower tumor grade (p< 0.001), but more lymph node metastases (p < 0.01). AR positivity was associated with prolonged disease free survival (HR 0.809, 95% CI = 0.659-0.995, p < 0.05), but had no significant impact on overall survival (HR 1.270, 95% CI=0.904-1.782, p = 0.168). No difference in survival existed between subgroups using different AR or estrogen receptor cutoff values.Materials and methodsLiterature search was performed in Pubmed, Embase and Cochrane Central Register of Controlled Trials databases to identify relevant articles on AR and TNBC prognosis. Fixed- and random-effect meta-analyses were conducted based on the heterogeneity of included studies. Heterogeneity and impacts of covariates were further evaluated by subgroup analyses and meta-regression.ConclusionAR positivity is associated with lower risk of disease recurrence in TNBC. Further clinical studies are warranted to clarify its prognostic role on TNBC recurrence and survival.

New genetic test reduces chemotherapy use in patients with early‐stage breast cancer

A new genetic test called MammaPrint (Agendia Inc USA, Irvine, Calif.) identified a large group of patients with early-stage breast cancer for whom 5-year distant metastasisfree survival was the same regardless of whether they received adjuvant chemotherapy, according to results from a randomized phase 3 clinical trial. The patients in the study population were considered to be at high risk of disease recurrence based on clinical and biological criteria. Results of the trial, known as MINDACT (Microarray In Node-negative and 1-3 positive lymph node Disease may Avoid ChemoTherapy), were presented at the American Association for Cancer Research Annual Meeting 2016, which was held April 16 to 20, 2016, in New Orleans, Louisiana. Most oncologists currently make recommendations for adjuvant chemotherapy based on common clinical and biological criteria such as patient age and disease stage and grade, as well as hormonal receptor and human epidermal growth factor receptor 2 status. The trial results provide evidence that using MammaPrint could change clinical practice by reducing the use of adjuvant chemotherapy and sparing many patients from an aggressive treatment they will not benefit from, says Martine Piccart, MD, PhD, who presented the data and is head of the medicine department at the Jules Bordet Institute in Brussels, Belgium. For the trial, Dr. Piccart and her colleagues at 111 centers in 9 countries enrolled 6693 women who had undergone surgery for early-stage breast cancer. All patients were categorized as being at low or high risk of disease recurrence in 2 ways: 1) through analysis of tumor tissue using MammaPrint to determine the genetic risk of occurance (G-low or G-high); and 2) using Adjuvant! Online, a tool that calculates the risk of breast cancer recurrence based on common clinical and biological criteria (C-low or C-high). Among the 3356 patients in the MINDACT trial who were categorized as being at high risk of disease recurrence based on common clinical and pathological criteria (C-high), treatment based on MammaPrint results reduced chemotherapy prescriptions by approximately 46%. The 5-year distant metastasis-free survival rate for the discordant G-low/C-high group was reported to be greater than 94% regardless of whether patients received chemotherapy. Of the total number of patients enrolled in the MINDACT trial, approximately 14% were able to avoid chemotherapy by using the test to assess risk when compared with using traditional clinical assessments. Participants were then divided into 4 groups: those with a low risk of disease recurrence by both assessment methods, those with a high risk of disease recurrence by both assessment methods, and patients with a high and low risk of disease recurrence based on MammaPrint and Adjuvant! Online findings. Patients in the low/low group were assigned to no chemotherapy whereas those patients in the high/high group received adjuvant chemotherapy. Patients in the other 2 groups were randomly assigned to receive either chemotherapy or no chemotherapy. In addition to being what to the authors' knowledge is the first prospective, randomized controlled clinical trial of a breast cancer recurrence assay with level 1A clinical evidence and the first prospective translational research study of this size among patients with breast cancer to report the results of a primary objective, the trial has created a huge resource for future research, Dr. Piccart says. She explains that participant tumor samples, blood samples, and clinical outcomes data could be used to gain a substantially better understanding of the biology of breast cancer.

Aggressive Regimens Reduce Risk of Recurrence After Successful Treatment of MDR-TB.

We sought to determine whether treatment with a "long aggressive regimen" was associated with lower rates of relapse among patients successfully treated for pulmonary multidrug-resistant tuberculosis (MDR-TB) in Tomsk, Russia. We conducted a retrospective cohort study of adult patients that initiated MDR-TB treatment with individualized regimens between September 2000 and November 2004, and were successfully treated. Patients were classified as having received "aggressive regimens" if their intensive phase consisted of at least 5 likely effective drugs (including a second-line injectable and a fluoroquinolone) used for at least 6 months post culture conversion, and their continuation phase included at least 4 likely effective drugs. Patients that were treated with aggressive regimens for a minimum duration of 18 months post culture conversion were classified as having received "long aggressive regimens." We used recurrence as a proxy for relapse because genotyping was not performed. After treatment, patients were classified as having disease recurrence if cultures grew MDR-TB or they re-initiated MDR-TB therapy. Data were analyzed using Cox proportional hazard regression. Of 408 successfully treated patients, 399 (97.5%) with at least 1 follow-up visit were included. Median duration of follow-up was 42.4 months (interquartile range: 20.5-59.5), and there were 27 recurrence episodes. In a multivariable complete case analysis (n = 371 [92.9%]) adjusting for potential confounders, long aggressive regimens were associated with a lower rate of recurrence (adjusted hazard ratio: 0.22, 95% confidence interval, .05-.92). Long aggressive regimens for MDR-TB treatment are associated with lower risk of disease recurrence.

The Clinical Research Office of the Endourological Society (CROES) Multicentre Randomised Trial of Narrow Band Imaging–Assisted Transurethral Resection of Bladder Tumour (TURBT) Versus Conventional White Light Imaging–Assisted TURBT in Primary Non–Muscle-invasive Bladder Cancer Patients: Trial Protocol and 1-year Results

BackgroundWhite light (WL) is the established imaging modality for transurethral resection of bladder tumour (TURBT). Narrow band imaging (NBI) is a promising addition. ObjectivesTo compare 12-mo recurrence rates following TURBT using NBI versus WL guidance. Design, setting, and participantsThe Clinical Research Office of the Endourological Society (CROES) conducted a prospective randomised single-blind multicentre study. Patients with primary non–muscle-invasive bladder cancer (NMIBC) were randomly assigned 1:1 to TURBT guided by NBI or WL. InterventionTURBT for NMIBC using NBI or WL. Outcome measurements and statistical analysisTwelve-month recurrence rates were compared by chi-square tests and survival analyses. Results and limitationsOf the 965 patients enrolled in the study, 481 patients underwent WL-assisted TURBT and 484 patients received NBI-assisted TURBT. Of these, 294 and 303 patients, respectively, completed 12-mo follow-up, with recurrence rates of 27.1% and 25.4%, respectively (p=0.585, intention-to-treat [ITT] analysis). In patients at low risk for disease recurrence, recurrence rates at 12 mo were significantly higher in the WL group compared with the NBI group (27.3% vs 5.6%; p=0.002, ITT analysis). Although TURBT took longer on average with NBI plus WL compared with WL alone (38.1 vs 35.0min, p=0.039, ITT; 39.1 vs 35.7min, p=0.047, per protocol [PP] analysis), lesions were significantly more often visible with NBI than with WL (p=0.033). Frequency and severity of adverse events were similar in both treatment groups. Possible limitations were lack of uniformity of surgical resection, data on smoking status, central pathology review, and specific data regarding adjuvant intravesical instillation therapy. ConclusionsNBI and WL guidance achieved similar overall recurrence rates 12 mo after TURBT in patients with NMIBC. NBI-assisted TURBT significantly reduced the likelihood of disease recurrence in low-risk patients. Patient summaryUse of a narrow band imaging technique might provide greater detection of bladder tumours and subsequent treatment leading to reduced recurrence in low-risk patients.

Determining optimal follow-up in the management of human papillomavirus-positive oropharyngeal cancer.

Determining the optimal follow-up for patients can help maximize the use of health care resources. This is particularly true in a growing epidemic such as human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV+OPSCC). The objective of the current study was to evaluate time to disease recurrence or late toxicity in this cohort of patients to optimize patient management. An institutional database identified 232 patients with biopsy-proven, nonmetastatic HPV+OPSCC who were treated with radiotherapy. A retrospective review was conducted in patients who were followed every 3 months for the first year, every 4 months in year 2, and every 6 months in years 3 to 5. Late toxicity (grade ≥ 3; toxicity was scored based on National Cancer Institute Common Terminology Criteria for Adverse Events [version 4]), locoregional control, distant control, and overall survival were assessed. The median follow-up was 33 months. Based on Radiation Therapy Oncology Group (RTOG) 0129 study risk groupings, patients were either considered to be at low (162 patients; 70%) or intermediate (70 patients; 30%) risk. Concurrent systemic therapy was used in 85% of patients (196 patients). The 3-year locoregional control, distant control, and overall survival rates were 94%, 91%, and 91%, respectively. Late toxicity occurred in 9% of patients (21 patients). Overall, 64% of toxicity and failure events occurred within the first 6 months of follow-up, with a < 2% event incidence noted at each subsequent follow-up. Only 4 patients experienced their first event after 2 years. HPV+OPSCC has a low risk of disease recurrence and late toxicity after treatment; approximately two-thirds of events occur within the first 6 months of follow-up. These data suggest that it may be reasonable to reduce follow-up in patients with HPV+OPSCC to every 3 months for the first 6 months, every 6 months for the first 2 years, and annually thereafter.

The ALTERNATE trial: assessing a biomarker driven strategy for the treatment of post-menopausal women with ER+/Her2- invasive breast cancer.

The Alliance for Clinical Trials in Oncology cooperative group has designed a phase III neoadjuvant clinical trial (ALTERNATE trial) which randomizes women with cT2-4 N0-3 M0 ER+/Her2- invasive breast cancer to either anastrozole, fulvestrant or its combination to assess a biomarker-driven treatment strategy to identify women with a low risk of disease recurrence. This strategy incorporates the findings that: higher expression of the proliferation marker, Ki67, after 2 weeks of neoadjuvant endocrine therapy (ET), is associated with poor recurrence-free survival, and that patients with surgical findings of pT1/2, pN0 disease, Ki67 ≤2.7% and ER Allred score of 3-8 after neoadjuvant ET have extremely low recurrence rates. We present a description and rationale for the design of this trial.

Preventive administration of UDCA after liver transplantation for primary biliary cirrhosis is associated with a lower risk of disease recurrence

Recurrence of primary biliary cirrhosis (PBC) after liver transplantation (LT) is not rare and can occasionally lead to severe graft dysfunction and retransplantation. Ursodeoxycholic acid (UDCA) is a safe and effective treatment for PBC. However, whether preventive administration of UDCA after LT could lower the incidence of PBC recurrence is unknown. Patients transplanted for PBC in five French and Swiss centers from 1988 to 2010 were included. Most patients from a single center received UDCA (10-15 mg/kg/d) preventively. Recurrence of PBC was histologically defined from biopsies routinely performed at 1, 5, 10, and 15 years of follow-up, and at any time when clinically indicated. A total of 90 patients with a 1-year minimum follow-up were studied retrospectively, including 19 (21%) patients receiving preventive UDCA. The mean follow-up was 12 years. Recurrence was diagnosed in 48 (53%) patients. The recurrence rates at 5, 10, and 15 years were 27%, 47%, and 61%, respectively. In a multivariate proportional hazards model adjusted for potential confounders and risk factors, preventive UDCA was the only factor affecting the risk of recurrence significantly (HR=0.32; 95% CI: 0.11-0.91). The 5, 10, and 15-year rates of recurrence were 11%, 21%, and 40%, respectively, under preventive UDCA, and 32%, 53%, and 70%, respectively, without preventive UDCA. Seven patients with recurrence (15%) progressed to cirrhosis, requiring retransplantation in one. However, neither recurrence nor preventive UDCA had a significant impact on survival. Preventive treatment with UDCA reduces the risk of PBC recurrence after LT.

Ultrasensitive Prostate Specific Antigen and its Role after Radical Prostatectomy: A Systematic Review

Prostate specific antigen is an important tool to monitor patients with prostate cancer after radical prostatectomy. Ultrasensitive prostate specific antigen assays are increasingly used with a lower limit of detection as low as 0.001 ng/ml. We systematically reviewed currently available ultrasensitive prostate specific antigen technologies and the role of this method in monitoring patients after radical prostatectomy. We searched the relevant literature using the MEDLINE® database. For various study objectives the series eligible for review provided serial ultrasensitive prostate specific antigen (lower detection limit less than 0.1 ng/ml) data on men after radical prostatectomy as well as comparative data on standard prostate specific antigen (lower detection limit 0.1 ng/ml or greater). Ultrasensitive prostate specific antigen could potentially detect prostate cancer recurrence years earlier than standard prostate specific antigen assays. The specificity of detectable ultrasensitive prostate specific antigen is low. Ultrasensitive prostate specific antigen kinetics may improve the positive predictive value for detecting cancer recurrence. However, the usefulness of prostate specific antigen doubling time at the ultrasensitive level remains controversial. Undetectable nadir ultrasensitive prostate specific antigen after radical prostatectomy confers a low risk of disease recurrence while a detectable nadir above 0.01 ng/ml requires additional measurement and consideration of other risk factors to determine management and avoid overtreatment. This monitoring method may spare patients with high risk disease adjuvant radiation therapy and enable more selective early salvage radiation. Currently no data demonstrate improved survival after early salvage therapy prompted by ultrasensitive prostate specific antigen surveillance. Ultrasensitive prostate specific antigen is useful in the early diagnosis of cancer recurrence after radical prostatectomy but specificity is poor. To date there is a lack of evidence that earlier detection of recurrence translates into prolonged time to metastasis. Integrating ultrasensitive prostate specific antigen with other clinicopathological factors can help determine optimal adjuvant and salvage therapy.

Integrating meta-analysis of microarray data and targeted proteomics for biomarker identification: application in breast cancer.

The development of signature biomarkers has gained considerable attention in the past decade. Although the most well-known examples of biomarker panels stem from gene expression studies, proteomic panels are becoming more relevant, with the advent of targeted mass spectrometry-based methodologies. At the same time, the development of multigene prognostic classifiers for early stage breast cancer patients has resulted in a wealth of publicly available gene expression data from thousands of breast cancer specimens. In the present study, we integrated transcriptome and proteome-based platforms to identify genes and proteins related to patient survival. Candidate biomarker proteins have been identified in a previously generated breast cancer tissue extract proteome. A mass-spectrometry-based assay was then developed for the simultaneous quantification of these 20 proteins in breast cancer tissue extracts. We quantified the relative expression levels of the 20 potential biomarkers in a cohort of 96 tissue samples from patients with early stage breast cancer. We identified two proteins, KPNA2 and CDK1, which showed potential to discriminate between estrogen receptor positive patients of high and low risk of disease recurrence. The role of these proteins in breast cancer prognosis warrants further investigation.

The role of protein p16(INK4a) in glottic laryngeal squamous cell carcinoma.

Head and neck squamous cell cancer (HNSCC) includes tumors of various anatomical sites sharing the common etiological factors. However some differences in pathogenesis and prognosis of HNSCC have been hitherto documented. Laryngeal squamous cell carcinoma (LSCC) is one the most common type of the head and neck cancer. The majority of laryngeal cancers are located in the glottic area. P16 was recently documented to be important prognostic marker in many tumors including HNSCC. The aim of our study was to assess the significance of p16 expression in glottic LSCC. Fifty eight patients after surgical treatment of the glottic LSCC were enrolled in the retrospective study. The p16 expression was immunohistochemically detected and semiquantitatively evaluated in tumor tissue. The results were statistically correlated with clinical and pathological parameters. Protein p16 was expressed in glottic LSCC of 15 patients (25.9%). Statistically significant higher p16 overexpression was proven in non-smokers in comparison with smokers (75% versus 18%; p =0.003). Recurrent cancer was diagnosed in 8 patients (13.8%), and all these tumors were p16 negative. Our study shows, that p16 expression in glottic LSCC especially in subgroup of non-smokers might be promising prognosticator of better clinical outcome in routine practice. The p16 status did not statistically correlate with cervical lymph node metastases or with grading and staging of cancers, respectively. The preliminary results suggest that p16 overexpression in glottic LSCC may identify patients at low risk of disease recurrence. However, the pathobiology of this tumor as well as predictive role of p16 expression in laryngeal cancer still remains to be better elucidated.

Effectiveness of different treatment modalities for the management of adult-onset granulosa cell tumours of the ovary (primary and recurrent).

Granulosa cell tumour is a rare gynaecological tumour of the ovary with recurrences many years after initial diagnosis and treatment. Evidence-based management of granulosa cell tumour of the ovary is limited, and treatment has not been standardised. Surgery, including fertility-sparing procedures for young women, has traditionally been the standard treatment. Adjuvant treatments following surgery have been based on non-randomised trials. A combination of bleomycin, etoposide and cisplatin (BEP) has traditionally been used for treatment of advanced and/or recurrent disease that cannot be optimally managed surgically. To evaluate the effectiveness and safety of different treatment modalities offered in current practice for the management of primary, residual and recurrent adult-onset granulosa cell tumours (GCTs) of the ovary. We searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE up to December 2013. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. We searched for randomised controlled trials (RCTs), quasi-RCTs and observational studies that examined women with adult-onset granulosa cell tumours of the ovary (primary and recurrent). For non-randomised studies, we included studies that used multivariate analysis to adjust for baseline characteristics. Two review authors independently abstracted data and assessed risk of bias. Studies were heterogeneous with respect to treatment comparisons, so data were not synthesised in meta-analyses, and methods for assessing heterogeneity were not needed. Risk of bias in included studies was assessed by using the six core items used to assess RCTs and by evaluating four additional criteria specifically addressing risk of bias in non-randomised studies. Five retrospective cohort studies (535 women with a diagnosis of GCT) that used appropriate statistical methods for adjustment were included in the review.Two studies, which carried out multivariate analyses that attempted to identify factors associated with better outcomes (in terms of overall survival), reported no apparent evidence of a difference in overall survival between surgical approaches, whether a participant underwent lymphadenectomy or received adjuvant chemotherapy or radiotherapy. Only percentage of survival for all participants combined was reported in two trials and was not reported at all in one study.One study showed that women who received postoperative radiotherapy had lower risk of disease recurrence compared with those who underwent surgery alone (adjusted hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.1 to 0.6, P value 0.04). Three studies reportedthat there was no evidence of differences in disease recurrence based on execution and type of adjuvant chemotherapy or on type of surgery or surgical approach, other than that surgical staging may be important. One study described no apparent evidence of a difference in disease recurrence between fertility-sparing surgery and conventional surgery. Recurrence-free survival was not reported in one study.Toxicity and adverse event data were incompletely reported in the five studies. None of the five studies reported on quality of life (QoL). All studies were at very high risk of bias. One study showed a lower recurrence rate with the use of adjuvant radiotherapy, although this study was at high risk of bias and the results should be interpreted with caution. After evaluating the five small retrospective studies, we are unable to reach any firm conclusions as to the effectiveness and safety of different types and approaches of surgery, including conservative surgery, as well as adjuvant chemotherapy or radiotherapy, for management of GCTs of the ovary. The available evidence is very limited, and the review provides only low-quality evidence. Further research is very likely to have an important impact on our confidence in the estimate of effect and may alter our findings.Ideally, multinational RCTs are needed to answer these questions. The disease is relatively rare and generally has a good prognosis. RCTs are challenging to conduct, but three ongoing trials have been identified, demonstrating that they are feasible, although two of these studies are single-arm trials. The study that may be able to provide answers to the question of which chemotherapeutic regimen should be selected for management of sex cord stromal tumours is an ongoing, randomised, phase 2 study, led by the Gynaecological Oncology Group to compare the efficacy of carboplatin and paclitaxel versus standard BEP. These investigators are also looking into the value of inhibin A and inhibin B as predictive biomarkers. Additional trials are required to assess toxicity and QoL associated with different treatment regimens as well as the safety of conservative surgical options.

Identification and Evaluation of the Salient Physical Activity Beliefs of Colorectal Cancer Survivors

Physical activity (PA) has been associated with lower risk of disease recurrence and longer survival in colorectal cancer (CRC) survivors; however, less than one-third of CRC survivors are meeting PA guidelines. Interventions to promote PA in CRC survivors need to understand the most critical beliefs that influence PA behavior. The objective of this study was to examine the strength of associations between the most common PA beliefs of CRC survivors and motivational constructs from the Theory of Planned Behavior (TPB) as well as PA behavior. Colorectal cancer survivors (n = 600) residing in Alberta, Canada, completed self-report questionnaires assessing medical and demographic variables, PA beliefs, constructs from the TPB, and PA behavior. Colorectal cancer survivors identified improved fitness (69.5%), family members (67.3%), and medical/health problems (8.8%) as the most prevalent behavioral, normative, and control beliefs, respectively. All PA beliefs were significantly correlated with all TPB constructs and PA. Physical activity interventions for CRC survivors should target many salient beliefs including behavioral, normative, and control beliefs. Insights into the salient beliefs for PA in CRC survivors can guide nurses in developing successful strategies to promote PA in this population and likely improve quality of life and possibly disease outcomes.

Association of diabetes mellitus and metformin use with oncological outcomes of patients with non‐muscle‐invasive bladder cancer

To assess the association between diabetes mellitus (DM) and metformin use with prognosis and outcomes of non-muscle-invasive bladder cancer (NMIBC) PATIENTS AND METHODS: We retrospectively evaluated 1117 patients with NMIBC treated at four institutions between 1996 and 2007. Cox regression models were used to analyse the association of DM and metformin use with disease recurrence, disease progression, cancer-specific mortality and any-cause mortality. Of the 1117 patients, 125 (11.1%) had DM and 43 (3.8%) used metformin. Within a median (interquartile range) follow-up of 64 (22-106) months, 469 (42.0%) patients experienced disease recurrence, 103 (9.2%) experienced disease progression, 50 (4.5%) died from bladder cancer and 249 (22.3%) died from other causes. In multivariable Cox regression analyses, patients with DM who did not take metformin had a greater risk of disease recurrence (hazard ratio [HR]: 1.45, 95% confidence interval [CI] 1.09-1.94, P = 0.01) and progression (HR: 2.38, 95% CI 1.40-4.06, P = 0.001) but not any-cause mortality than patients without DM. DM with metformin use was independently associated with a lower risk of disease recurrence (HR: 0.50, 95% CI 0.27-0.94, P = 0.03). Patients with DM and NMIBC who do not take metformin seem to be at an increased risk of disease recurrence and progression; metformin use seems to exert a protective effect with regard to disease recurrence. The mechanisms behind the impact of DM on patients with NMIBC and the potential protective effect of metformin need further elucidation.

Current role of neoadjuvant and adjuvant systemic therapy for high-risk localized prostate cancer.

Although most men are diagnosed with readily curable localized prostate cancer, those with high-risk features face a significant mortality risk. Androgen deprivation therapy (ADT) is a standard adjunct to radiotherapy for high-risk prostate cancer, but its role around prostatectomy has not been as clearly defined, and concerns over cardiovascular toxicity have led to decreasing use. The use of chemotherapy for localized disease remains experimental. We review the most recently published trials of neoadjuvant or adjuvant systemic therapy for prostate cancer. The optimal duration of ADT with higher dose modern radiation techniques is under active investigation, but current data support the use of longer duration as standard. Prostate-specific antigen (PSA) and MRI changes may be useful in future studies optimizing duration of neoadjuvant ADT. Two years of combined ADT after prostatectomy is associated with a lower risk of disease recurrence and better prostate cancer specific mortality than predicted. Persistence of intraprostatic androgens during neoadjuvant ADT may contribute to resistance. Androgen deprivation added to definitive radiation or surgery improves outcomes for high-risk prostate cancer, although the role of chemotherapy remains undefined. Molecular classification is needed to improve risk stratification.

Tailoring treatment and trials to prognosis

As we learn more about the biology of cancer, we may be able to apply prognostic biomarkers to select patients at high risk or low risk of disease recurrence or progression. This will allow a priori stratification of patients in clinical trials and will help to tailor treatment to patients.

Special Issue on Precision Risk Stratification-Based Screening in Colorectal Cancer

Cancer remains a formidable public health burden, as over half a million Americans succumb to this disease each year. The fight to vanquish cancer is stronger than ever. The pace of acquisition of new, cutting-edge scientific knowledge about the complex biology of cancer, and the development of technologies, targeted therapeutics and innovative approaches to prevent, detect and treat the disease have accelerated considerably over the past decade. Hence, in just over a century we have witnessed an extraordinary evolution of medical practice from seeking to understand disease in a physician-directed healthcare paradigm, to evidence-based medicine, and on to the modern era of emerging personalized, predictive, precision medicine (which applies predictive and prognostic biomarkers and patient-specific attributes using a “personalized lifespan approach”). During the past year we have witnessed not only a multi-faceted national effort to improve quality and value of cancer care aligned with the Institute for Healthcare Improvement's “triple aim” Initiative [improving the individual patient care experience, the health of populations, and thereby the efficiency and cost of care], but also realized several major clinical advances in cancer treatment [http://www.ihi.org/offerings/Initiatives/TripleAim/Pages/default.aspx]. In 2012 alone, the FDA approved seven new targeted systemic agents and expanded the anti-cancer indications for five existing agents. Noteworthy progress has been made in overcoming treatment resistance (combining targeted drugs, use of multi-targeted agents, targeting new pathways), understanding molecular drivers of cancer and tumor heterogeneity across the genomic landscape to include gene-environment interactions, advancing precision medicine, improving and enabling risk stratification-based screening and early detection. To this latter point, a minimally invasive technique (flexible sigmoidoscopy) has been shown in a large randomized clinical trial to significantly reduce both incidence (by 21%; relative risk, 0.79; 95% confidence interval [CI], 0.72 to 0.85; P<0.001) and overall colorectal cancer mortality (by 26%; relative risk, 0.74; 95% CI, 0.63 to 0.87; P<0.001) [N Engl J Med. 2012 Jun 21;366(25):2345-57]. This represents a major advance in cancer screening and early disease detection. It is decidedly poised to transform population-based screening, and to support concerted efforts to unravel socioeconomic disparities in cancer screening. What's more, this safe and effective screening approach will be used to educate screening populations about the importance of early detection, and could inspire wide-ranging compliance with recommended colorectal screening guidelines. The current special edition of the Journal of Cancer is centered on colorectal cancer and it highlights advances made in the prevention, screening, early detection, and treatment of this disease. It communicates an ambitious vision aimed at conquering colorectal cancer, and provides recommendations for leveraging innovative technological advances, particularly those that provide insights into patient-specific tumor biology, genetic make-up and epigenetic regulation. It emphasizes the way forward through progress made in screening for colorectal cancer in an ethnically and socio-economically diverse population with equal access to care. The special edition further emphasizes safe, effective, quality-based, innovative colorectal cancer care early detection and individualized precision medicine through Precision Risk Stratification-Based Screening. The principal aim of this risk identification and screening approach is to identify patients at risk for or diagnoses patients early in the natural history of colorectal cancer. It further defines evidence-based methods by which to avoid the toxicity of systemic therapy in appropriately risk-stratified patients identified as low risk for disease recurrence that are likely cured by surgery alone; appropriately classify patients with clinically latent or stable residual disease for whom systemic therapy can be withheld, and accurately recognize those high-risk node-negative patients with colorectal cancer or those with treatment-responsive disease likely to progress and treat them at the optimal time in the course of their disease. This special edition charts an ambitious and attainable way forward, and allows us ample basis by which to imagine a world without cancer.

ABVD alone and a PET scan complete remission negates the need for radiologic surveillance in early‐stage, nonbulky Hodgkin lymphoma

Patients with early-stage, nonbulky classic Hodgkin lymphoma (cHL) undergo intensive posttreatment radiologic surveillance despite having a low risk of disease recurrence. The current study attempted to evaluate the risk of disease recurrence and the value of radiologic surveillance in patients treated with the combination of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) alone who achieved a complete remission (CR) as noted on posttreatment positron emission tomography (PET). Forty-seven patients who underwent therapy with interim and/or posttreatment PET scans were evaluated for disease recurrence during ≥ 24 months of follow-up. Their presenting characteristics and imaging results were assessed and interpreted in relation to clinical outcome. All 47 patients were eligible for analysis. The majority of patients were female (35 patients) with a median age of 28 years (range, 17 years-65 years.). The nodular sclerosing subtype was the predominant histology (41 patients). A total of 34 patients were staged with IIA disease, 6 with IA disease, 6 with IIB disease, and 1 with IIEA disease (lung) (according to Cotswolds modification of the Ann Arbor staging system). All patients completed 6 cycles of planned ABVD therapy and achieved a CR. Two had a positive PET scan (1 interim scan and 1 posttreatment scan); both were biopsy-proven sarcoidosis. Two patients developed disease recurrence at 7 months and 24 months, respectively, after negative interim and posttreatment imaging. One case of recurrence was identified through surveillance imaging and the other was identified simultaneously by the patient and surveillance scan. A total of 45 patients experienced a durable CR; 21 had additional unscheduled imaging/workup during surveillance to investigate symptoms or imaging signs of concern. Because of a low risk of disease recurrence, posttreatment radiologic surveillance appears to be unnecessary in patients with early-stage, nonbulky (CD20 negative) cHL who achieve a PET-detected CR with the ABVD combination alone. This will reduce cumulative radiation exposure and health care costs in a predominantly young patient population.