Curr. Oncol., Volume 20, Issue 6 (December 2013) – 23 articles

Background: Cancer can be a devastating diagnosis. In particular, malignancy and its indicated treatments have profoundly negative effects on the fertility of young cancer patients. Oncofertility has emerged as a new interdisciplinary field to address the issue of gonadotoxicity associated with cancer therapies and to facilitate fertility preservation. In Canada, fertility issues are often inadequately addressed despite the availability of resources. The goal of this four-part series is to facilitate systemic improvements in fertility preservation for adolescent and young adult Canadians with a new diagnosis of cancer. Methods: Here, we review the fertility preservation measures currently available. Medical and surgical strategies are both outlined. Results: Fertility-preserving strategies and gonadal protection have demonstrated variable success in a number of approaches. The value of hormone suppression is still in question for women. Progestins for endometrial cancer and alternative chemotherapies are other medical approaches. Gonadal shielding and protective surgical approaches have also been attempted. Conclusions: The techniques discussed here may be selectively considered and integrated into patient care in an attempt to preserve future fertility before initiating cancer treatment. Full article

Multiple randomized trials have demonstrated that breast-conserving therapy with partial mastectomy and radiotherapy provides survival equivalent to that seen with mastectomy for patients with early-stage breast cancer. Breast-conserving therapy has been associated with better quality of life relative to mastectomy and has become the standard of care for patients with early-stage breast cancer. Young age has been identified as a risk factor for recurrence and death from breast cancer. Some studies have suggested that young women (less than 35 or 40 years of age) have inferior outcomes with breast-conserving therapy, implying that such women may be better served by mastectomy. On review of the available literature, there is no definitive evidence that mastectomy provides a consistent, unequivocal recurrence-free or overall survival benefit over breast-conserving therapy. However, available meta-analyses have not compared outcomes in young women specifically, and such analyses should be performed. In the interim, breast-conserving therapy is not contraindicated in young women (less than 40 years of age) and can be used cautiously; however, such women should be advised of the lack of unequivocal data proving that survival is equivalent to that with mastectomy in their age group. Full article

Objective and Methods: We retrospectively analyzed clinicopathologic features and survival in breast cancer patients who had T1 or T2 primary tumours and 1–3 histologically involved axillary lymph nodes and who were treated with modified radical mastectomy without adjuvant radiotherapy (RT). We also explored prognosis to find the high- and low-risk groups. Results: From May 2001 to April 2005, 368 patients treated at Tianjin Tumor Hospital met the study criteria. The 5- and 8-year rates were 7.2% and 10.7% for locoregional recurrence (LRR), 85.1% and 77.7% for disease-free survival (DFS), and 92.8% and 89.3% for overall survival (OS). Multivariate Cox regression analysis showed that age, tumour size, estrogen receptor (ER) status, and lymphovascular invasion (LVI) were independent prognostic factors for LRR and DFS. Based on 4 patient-related factors that indicate poor prognosis (age < 40 years, tumour > 3 cm, ER negativity, and LVI), the high-risk group (patients with 3 or 4 factors, accounting for 12.5% of the cohort) had 5- and 8-year rates of 24.3% and 36.9% for LRR, 57.2% and 39.2% for DFS, and 74.8% and 43.8% for OS compared with 5.0% and 7.1% for LRR, 88.9% and 83.1% for DFS, 91.6% and 83.4% for OS in the low-risk group (patients with 0–2 factors, accounting for 87.5% of the cohort; p < 0.001). Conclusions: Our study identified several risk factors that correlated independently with a greater incidence of LRR and distant metastasis in patients with T1 and T2 breast cancer and 1–3 positive nodes. Patients with 0–2 risk factors may not be likely to benefit from post-mastectomy RT, but patients with 3–4 risk factors may need RT to optimize locoregional control and improve survival. Full article

Purpose: We used a superficial parotid lobe–sparing delineation approach for dose optimization with better protection for the parotid glands in intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) patients. Methods: Compared with traditional contouring of the entire parotid glands as organs at risk (OARS) in IMRT for NPC, we used a superficial parotid lobe–sparing delineation approach of contouring the superficial parotid lobes as OARS. Changes in dose to the parotid glands, the targets, and other OARS were evaluated. Results: The mean dose to the parotid glands overall decreased by more than 4 Gy in the test plans. Impressively, the mean dose to the superficial parotid lobes in the test plans was not more than 30 Gy, regardless of clinical stage. In T1–3 NPC patients, the dose distributions for targets were not significantly different in the control plans and the test plans. However, for some T4 patients, the dose distributions for targets and brainstem in the test plans could not meet clinical requirements. Conclusions: The superficial parotid lobe–sparing delineation approach can significantly lower the mean dose to the entire parotid and to the superficial parotid lobe in T1–3 NPC patients, which would be expected to result in less xerostomia and better quality of life for those patients. Full article

Background: The Distress Thermometer (DT) is a screening tool recommended to quickly identify cancer patients with distress. Our study aimed to examine the sensitivity and specificity of the DT in detecting psychological distress in long-term Chinese nasopharyngeal cancer (NPC) survivors. Methods: Data for the 442 participating NPC survivors were collected through a self-administered questionnaire based on the DT and the Hospital Anxiety and Depression Scale (HADS). The HADS was used to define cases of psychological distress. Positive and negative groups were defined based on 4 HADS criteria (Anxiety, Depression, Anxiety or Depression, and overall score). Receiver operating characteristic (ROC) curves were used to examine the ability of all possible cut-off values of the DT to detect positive and negative cases. For each ROC curve, the area under the curve (AUC) was used as an indicator of the overall accuracy of the DT to identify positive cases of distress. Results: The positive AUC values [with 95% confidence intervals (CI)] for the 4 HADS criteria were 0.715 (95% CI: 0.667 to 0.764), 0.714 (95% CI: 0.661 to 0.768), 0.724 (95% CI: 0.677 to 0.771), and 0.724 (95% CI: 0.664 to 0.775) respectively. At a cut-off score of 4, the sensitivity of the DT to the four HADS criteria was, respectively, 0.366 (95% CI: 0.296 to 0.436), 0.448 (95% CI: 0.364 to 0.532), 0.362 (95% CI: 0.299 to 0.425), and 0.421 (95% CI: 0.339 to 0.502), and the specificity of the DT to the 4 HADS criteria was, respectively, 0.860 (95% CI: 0.818 to 0.902), 0.860 (95% CI: 0.821 to 0.899), 0.854 (95% CI: 0.814 to 0.894), and 0.854 (95% CI: 0.814 to 0.894). At a cut-off score of 5, the corresponding sensitivities were lower than those at the cut-off score of 4. All potential cut-off scores showed poor sensitivity (<0.90). Conclusions: The ROC analysis showed poor discrimination. No potential DT cut-off score had an acceptable sensitivity. The DT showed poor sensitivity in NPC survivors. Thus, the DT might not be a valid scale for psychological distress screening in long-term Chinese NPC survivors. Full article

Background: There is interest in the use of health information technology in the form of personal health record (PHR) systems to support patient needs for health information, care, and decision-making, particularly for patients with distressing, chronic diseases such as prostate cancer (PCa). We sought feedback from PCa patients who used a PHR. Methods: For 6 months, 22 PCa patients in various phases of care at the BC Cancer Agency (BCCA) were given access to a secure Web-based PHR called PROVIDER, which they could use to view their medical records and use a set of support tools. Feedback was obtained using an end-of-study survey on usability, satisfaction, and concerns with PROVIDER. Site activity was recorded to assess usage patterns. Results: Of the 17 patients who completed the study, 29% encountered some minor difficulties using PROVIDER. No security breaches were known to have occurred. The two most commonly accessed medical records were laboratory test results and transcribed doctor’s notes. Of survey respondents, 94% were satisfied with the access to their medical records, 65% said that PROVIDER helped to answer their questions, 77% felt that their privacy and confidentiality were preserved, 65% felt that using PROVIDER helped them to communicate better with their physicians, 83% found new and useful information that they would not have received by talking to their health care providers, and 88% said that they would continue to use PROVIDER. Conclusions: Our results support the notion that phrs can provide cancer patients with timely access to their medical records and health information, and can assist in communication with health care providers, in knowledge generation, and in patient empowerment. Full article

Objective: Malnutrition and psychological distress are often seen in patients with head-and-neck cancer, but little is known about the interrelationships between those two symptoms. The present study examined the relationship between malnutrition and psychological distress in patients with advanced head-and-neck cancer. Methods: Using the Patient-Generated Subjective Global Assessment, 99 patients with advanced-stage head-and-neck cancer were screened for nutrition status. The patients were also screened for psychosocial distress (using the Distress Thermometer) and for psychosocial issues (using the Problem Checklist). Any relationship between malnutrition and psychosocial distress was determined by regression and correlation analysis. We also used t-tests to compare distress levels for patients with and without specific nutrition-related symptoms. Results: The study group included 80 men and 19 women [mean age: 58.4 ± 10.9 years (range: 23–85 years)]. The correlation between poorer nutrition status and level of psychological distress was significant r = 0.37 (p < 0.001). Specifically, reduced food intake and symptoms were both positively associated with distress: r = 0.27 and r = 0.29 respectively, both significant at p < 0.01. After controlling for the effects of psychosocial problems and pain, nutrition status remained a significant predictor of distress, explaining 3.8% of the variance in the distress scores of the patients (p < 0.05). Conclusions: Malnutrition and symptoms were strongly related to distress in patients with advanced head-and-neck cancer. Our results suggest the need for further research into the complex relationship between nutrition status and distress and into the management of both nutrition and distress in cancer care. Full article

Objective: We investigated the prognostic clinicopathologic factors associated with overall survival (OS) and progression-free survival (PFS) in the once-daily continuous administration of first-line sunitinib in a consecutive cohort of Turkish patients with metastatic renal cell carcinoma (RCC). Methods: The study enrolled 77 Turkish patients with metastatic RCC who received sunitinib in a continuous once-daily dosing regimen between April 2006 and April 2011. Univariate analyses were performed using the log-rank test. Results: Median follow-up was 18.5 months. In univariate analyses, poor PFS and OS were associated with 4 of the 5 factors in the Memorial Sloan–Kettering Cancer Center (MSKCC) score: Eastern Cooperative Oncology Group performance status of 2 or higher, low hemoglobin, high corrected serum calcium, and high lactate dehydrogenase. In addition to those factors, hypoalbuminemia, more than 2 metastatic sites, liver metastasis, non–clear cell histology, and the presence of sarcomatoid features on pathology were also associated with poor PFS; and male sex, hypoalbuminemia, prior radiotherapy, more than 2 metastatic sites, lung metastasis, nuclear grade of 3 or 4 for the primary tumour, and the presence of sarcomatoid features were also associated with poorer OS. The application of the MSKCC model distinctly separated the PFS and OS curves (p < 0.001). Conclusions: Our study identified prognostic factors for PFS and OS with the use sunitinib as first-line metastatic RCC therapy and confirmed that the MSKCC model still appears to be valid for predicting survival in metastatic RCC in the era of molecular targeted therapy. Full article

Breast cancer is heterogenous, with variable expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Overexpression of HER2 is generally considered a negative prognostic feature, but whether outcomes for HER2-positive early breast cancer remain different from those for other subtypes in the era of trastuzumab-based adjuvant therapy is unknown. Methods: Using a retrospective chart review, we compared overall survival (OS) and relapse-free survival (RFS) in 3 groups of patients with early-stage breast cancer: ER-positive or PR-positive (or both) and HER2-negative [“hormone receptor–positive” (HR+)]; HER2-positive (HER2+); and ER-negative, PR-negative, and HER2-negative [“triple-negative” (TN)]. Results: In the 503 charts analyzed (332 HR+, 94 HER2+, 77 TN), the 5-year OS and RFS were, respectively, 94.2% and 87.2% for HR+ patients, 88.6% and 74.9% for HER2+ patients, and 85.4% and 76.2% for TN patients. On multivariate analysis, the OS for the HER2+ subtype was similar to that for the HR+ subtype (hazard ratio:1.07; 95% confidence interval: 0.31 to 3.67 with HR+ as reference), but OS was significantly worse for TN patients than for HR+ patients (hazard ratio: 4.37; 95% confidence interval: 1.56 to 12.24). In HER2+ patients, the 5-year OS and RFS trended better for patients with ER+ or PR+ disease than for patients with ER-negative and PR-negative disease (5-year OS: 92.1% vs. 86.9%; 5-year RFS: 79.8% vs. 71.4%). Of HER2+ patients, just 80.9% received trastuzumab, including 33.3% of HER2+ patients with sub-centimetre tumours. Conclusions: In the trastuzumab era, patients with HER2+ and HR+ early breast cancer have similar outcomes, while TN patients experience a significantly worse OS than either of the foregoing groups. Outcomes for HER2+ patients may differ by ER and PR status. Trastuzumab was underutilized in this cohort. Full article

Background: Patients with cancer are often treated with glucocorticoids (GCS) as part of therapy, which may cause hyperglycemia. We sought to define the prevalence of, and risk factors for, hyperglycemia in this setting. Methods: Adult patients taking GC as part of therapy protocols for primary brain tumour or metastasis, for lymphoma, or for bone marrow transplant (BMT) were screened with random glucometer measurements taken at least 3 hours after the last dose GCS. Results: We screened 90 patients [44.4% women, 55.6% men; mean age: 59.6 years (range: 25–82 years); mean body mass index (BMI): 26.4 kg/m2 (range: 15.8–45.3 kg/m2)] receiving GC as part of cancer treatment. Mean total daily GC dose in the group was 238.5 mg (range: 30–1067 mg) hydrocortisone equivalents. Hyperglycemia (glucose ≥ 8.0 mmol/L) was found in 58.9% (53 of 90), and diabetes mellitus (DM)–range hyperglycemia (glucose ≥ 11.1 mmol/L) in 18.9% (17 of 90). The mean time from GC ingestion to glucometer testing was 5.5 hours (range: 3–20 hours). Presence of hyperglycemia did not correlate with traditional DM risk factors such as age, sex, BMI, and personal or family history of DM. A longer interval from GC dose to testing (p < 0.05), a higher GC dose (p = 0.04), and a shorter interval between the preceding meal and testing (p = 0.02) were risk factors for hyperglycemia in some patient groups. Conclusions: Glucocorticoid-induced hyperglycemia is common in patients undergoing cancer treatment and cannot be predicted by traditional risk factors for DM. We recommend that all cancer patients receiving GC be screened for hyperglycemia at least 4–6 hours after GC administration. Full article

Background: Prostate cancer (pca) is the most common non-skin cancer among men in Canada and other Western countries. Increased prevalence and higher cost of newer treatments have led to a significant rise in the economic burden of pca. The objectives of the present study were to systematically review the literature on direct costs for the initial management of pca, and to examine the methodologic considerations across studies. Methods: Bibliographic databases were systematically searched for peer-reviewed articles in English. Studies were reviewed for methodologic considerations and mean direct cost of active surveillance or watchful waiting (as/ww) and initial treatments. Direct cost was standardized to 2011 Canadian dollars. Results: After a review of abstracts and full-text papers, seventeen articles met the eligibility criteria and were included in the review. Studies were published during 1992–2010. The studies reported on health care systems in the United States, France, the United Kingdom, German, Italy, and Spain. Our review identified a lack of methodologic consensus, leading to variation in direct costs between studies. Nevertheless, results indicate a significant direct cost of pca treatments. Conclusions: The existing literature lacks methodologically rigorous studies on the direct costs of pca treatments specific to publicly funded health care systems. Additional studies are required to appreciate the direct costs of newer treatments and the impact of their adoption on the growing economic burden of pca management. Full article

Health services researchers have consistently identified a gap between what is identified as “best practice” and what actually happens in clinical care. Despite nearly two decades of a growing evidence-based practice movement, narrowing the knowledge–practice gap continues to be a slow, complex, and poorly understood process. Here, we contend that cross-disciplinary research is increasingly relevant and important to reducing that gap, particularly research that encompasses the notion of transdisciplinarity, wherein multiple academic disciplines and non-academic individuals and groups are integrated into the research process. The assimilation of diverse perspectives, research approaches, and types of knowledge is potentially effective in helping research teams tackle real-world patient care issues, create more practice-based evidence, and translate the results to clinical and community care settings. The goals of this paper are to present and discuss cross-disciplinary approaches to health research and to provide two examples of how engaging in such research may optimize the use of research in cancer care. Full article

Background: Healthy lifestyle behaviours may improve outcomes for people with colorectal cancer (CRC), but the intention to take action and to change those behaviours may vary with time and resource availability. We aimed to estimate the prevalence of current lifestyle behaviours in people with and without CRC in our community, and to identify their desire to change and their resource preferences. Methods: A mixed-methods survey was completed by people diagnosed with CRC who were pre-treatment (n = 54), undergoing treatment (n = 62), or done with treatment for less than 6 months (n = 67) or for more than 6 months (n = 178), and by people without cancer (n = 83). Results: Current lifestyle behaviours were similar in all groups, with the exception of vigorous physical activity levels, which were significantly lower in the pre-treatment and ongoing treatment respondents than in cancer-free respondents. Significantly more CRC respondents than respondents without cancer had made lifestyle changes. Among the CRC respondents, dietary change was the change most frequently made (39.3%), and increased physical activity was the change most frequently desired (39.1%). Respondents wanted to use complementary and alternative medicine (CAM), reading materials, self-efficacy, and group activities to make future changes. Conclusions: Resources for lifestyle change should be made available for people diagnosed with CRC, and should be tailored to address physical activity, CAM, and diet. Lifestyle programs offered throughout the cancer trajectory and beyond treatment completion might be well received by people with CRC. Full article

Purpose: Imaging by fluorodeoxyglucose positron-emission tomography (PET) has emerged as a valuable tool in the management of locally advanced cervical cancer (LACC), both for assessment of lymph node status and determination of response to chemoradiotherapy. The aim of the present study was to survey Canadian radiation oncologists to determine access to PET imaging for LACC patients and to assess current patterns of practice. Methods: Radiation oncology centres across Canada were contacted to identify radiation oncologists who treat patients with LACC. The focus of the survey was patients treated with radical chemoradiotherapy with curative intent. An anonymous online tool was used to distribute a 23-item questionnaire asking about access to PET imaging, opinions on indications for PET imaging, and practice patterns relating to the use of PET in this patient population. Questionnaire responses were tabulated and analyzed. Results: The response rate was 65% (35 of 54 questionnaire recipients). Most respondents (80%) have access to PET for LACC patients, usually restricted to study protocols. Of the respondents, 48% considered that access to PET was timely. Frequency of routine orders for PET before and after treatment (to assess response) was 63% and 15% respectively. With better access, 91% of respondents would routinely order PET before treatment, and 61% would routinely order it for posttreatment assessment. For initial staging, 85% of respondents considered PET to be a standard of care, and nearly half (45%) believed it should be a standard of care to assess treatment response. Because of access limitations, nearly 70% of respondents (23 of 34) do not order pet as often as they feel it is clinically indicated, and 74% agree that better access to PET would lead to improved care for LACC patients in Canada. Conclusions: Canadian radiation oncologists support the routine use of PET imaging in the initial workup of patients with LACC. Access to PET imaging limits routine use for these patients in clinically indicated situations. There is strong support for developing guidelines for PET use in this patient population. Full article

Background: The survival benefit for single-agent anti–epidermal growth factor receptor (EGFR) therapy compared with combination therapy with irinotecan in KRAS wildtype (wt) metastatic colorectal cancer (mCRC) patients in the third-line treatment setting is not known. The objective of the present study was to describe the characteristics of, and to compare survival outcomes in, two cohorts of patients treated with either singleagent panitumumab or combination therapy with cetuximab and irinotecan. Methods: The study enrolled patients with KRAS wt mCRC previously treated with both irinotecan and oxaliplatin who had received either panitumumab or combination cetuximab–irinotecan before April 1, 2011, at the BC Cancer Agency (BCCA). Patients were excluded if they had received anti-EGFR agents in earlier lines of therapy. Data were prospectively collected, except for performance status (PS), which was determined by chart review. Information about systemic therapy was extracted from the BCCA Pharmacy Database. Results: Of 178 eligible patients, 141 received panitumumab, and 37 received cetuximab–irinotecan. Compared with patients treated with cetuximab–irinotecan, panitumumab-treated patients were significantly older and more likely to have an Eastern Cooperative Oncology Group (ECOG) PS of 2 or 3 (27.7% vs. 2.7%, p = 0.001). Other baseline prognostic variables and prior and subsequent therapies were similar. Median overall survival was 7.7 months for the panitumumab group and 8.3 months for the cetuximab–irinotecan group. Multivariate analysis demonstrated that survival outcomes were similar regardless of the therapy selected (hazard ratio: 1.28; p = 0.34). An ECOG PS of 2 or 3 compared with 0 or 1 was the only significant prognostic factor in this treatment setting (hazard ratio: 3.37; p < 0.01). Conclusions: Single-agent panitumumab and cetuximab–irinotecan are both reasonable third-line treatment options, with similar outcomes, for patients with chemoresistant mCRC. Full article

Objective: To be useful to policymakers and stakeholders, cost-effectiveness analyses (CEAS) should be published in a timely manner and without bias. The aims of the present study were to examine the time between conference abstract presentation and subsequent publication, to determine the factors associated with time to publication, to evaluate potential publication bias, and to examine discrepancies in the results between abstract and publication. Methods: Abstracts of CEAS presented at the annual meetings of the American Society of Clinical Oncology (ASCO), the American Society of Hematology (ASH), and the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) between 1997 and 2007 were reviewed. Time-to-event analysis was performed to assess the timeliness of publication and to examine factors associated with time to publication. Summary statistics were used to assess discrepancies in incremental cost-effectiveness ratios (ICERS) between abstract and publication. Results: Of 164 abstracts identified, 65 (39.6%) were subsequently published. The 1-, 2-, 3-, and 5-year publication rates were 12.8%, 25%, 34.2%, and 40.5% respectively. Abstracts were more likely to be published if presented at ASCO than at ISPOR (hazard ratio: 1.94; p = 0.038). There was no direct evidence of publication bias for abstracts with favourable ICERS. Comparing ICERS between abstracts and publications, the mean absolute difference was 23.8%; 50% of studies had a change in ICER exceeding 10%. Conclusions: Publication rates for CEAS were low, and publication was not timely with respect to informing the decision-making process for funding. Abstract results often differed from publication results and cannot reliably be used in the decision-making process for funding. Full article

Background: Cancer can affect many dimensions of a patient’s life, and in turn, it should be targeted using a multimodal approach. We tested the extent to which an interdisciplinary nutrition–rehabilitation program can improve the well-being of patients with advanced cancer. Methods: Between January 10, 2007, and September 29, 2010, 188 patients with advanced cancer enrolled in the 10–12-week program. Body weight, physical function, symptom severity, fatigue dimensions, distress level, coping ability, and overall quality of life were assessed at the start and end of the program. Results: Of the enrolled patients, 70% completed the program. Patients experienced strong improvements in the physical and activity dimensions of fatigue (effect sizes: 0.8–1.1). They also experienced moderate reductions in the severity of weakness, depression, nervousness, shortness of breath, and distress (effect sizes: 0.5–0.7), and moderate improvements in Six Minute Walk Test distance, maximal gait speed, coping ability, and quality of life (effect sizes: 0.5–0.7) Furthermore, 77% of patients either maintained or increased their body weight. Conclusions: Interdisciplinary nutrition–rehabilitation can be advantageous for patients with advanced cancer and should be considered an integrated part of standard palliative care. Full article

Background: After treatment, patients with active cancer face a considerable burden from the effects of both the disease and its treatment. The Palliative Rehabilitation Program (PRP) is designed to ameliorate disease effects and to improve the patient’s functioning. The present study evaluated predictors of program completion and changes in functioning, symptoms, and well-being after the program. Methods: The program received referrals for 173 patients who had finished anticancer therapy. Of those 173 patients, 116 with advanced cancer were eligible and enrolled in the 8-week interprofessional PRP; 67 completed it. Measures of physical, nutritional, social, and psychological functioning were evaluated at entry to the program and at completion. Results: Participants experienced significant improvements in physical performance (p < 0.000), nutrition (p = 0.001), symptom severity (p = 0.005 to 0.001), symptom interference with functioning (p = 0.003 to 0.001), fatigue (p = 0.001), and physical endurance, mobility, and balance or function (p = 0.001 to 0.001). Reasons that participants did not complete the PRP were disease progression, geographic inaccessibility, being too well (program not challenging enough), death, and personal or unknown reasons. A normal level of C-reactive protein (<10 mg/L, p = 0.029) was a predictor of program completion. Conclusions: Patients living with advanced cancers who underwent the interprofessional PRP experienced significant improvement in functioning across several domains. Program completion can be predicted by a normal level of C-reactive protein. Full article