What is the quality of economic evaluations of non-drug therapies? A systematic review and critical appraisal of economic evaluations of radiotherapy for cancer. Applied Health Economics and Health Policy.

Background Breast, cervical and colorectal cancers are the three most frequent cancers in women, while lung, prostate and colorectal cancers are the most frequent in men. Much attention has been given to the economic evaluation of pharmaceuticals for treatment of cancer by the National Institute for Health and Care Excellence (NICE) in the UK and similar authorities internationally, while economic analysis developed for other types of anti-cancer interventions, including radiotherapy and surgery, are less common. Objectives Our objective was to review methods used in published cost-effectiveness studies evaluating radiotherapy for breast, cervical, colorectal, head and neck and prostate cancer, and to compare the economic evaluation methods applied with those defined in the guidelines used by the NICE technology appraisal programme. Methods A systematic search of seven databases (MEDLINE, EMBASE, CDSR, NHSEED, HTA, DARE, EconLit) as well as research registers, the NICE website and conference proceedings was conducted in July 2012. Only economic evaluations of radiotherapy interventions in individuals diagnosed with cancer that included quality-adjusted life-years (QALYs) or life-years (LYs) were included. Included studies were appraised on the basis of satisfying essential, preferred and UK-specific methods requirements, building on the NICE Reference Case for economic evaluations and on other methods guidelines. Results A total of 29 studies satisfied the inclusion criteria (breast 14, colorectal 2, prostate 10, cervical 0, head and neck 3). Only two studies were conducted in the UK (13 in the USA). Among essential methods criteria, the main issue was that only three (10 %) of the studies used clinical-effectiveness estimates identified through systematic review of the literature. Similarly, only eight (28 %) studies sourced health-related quality-of-life data directly from patients with the condition of interest. Other essential criteria (e.g. clear description of comparators, patient group indication and appropriate time horizon) were generally fulfilled, while most of the UK-specific requirements were not met. Conclusion Based on this review there is a dearth of up-to-date, robust evidence on the cost effectiveness of radiotherapy in cancer suitable to support decision making in the UK. Studies selected did not fully satisfy essential method standards currently recommended by NICE

ACR Appropriateness Criteria® Spinal Bone Metastases

The spine is a common site of involvement in patients with bone metastases. Apart from pain, hypercalcemia, and pathologic fracture, progressive tumor can result in neurologic deterioration caused by spinal cord compression or cauda equina involvement. The treatment of spinal bone metastases depends on histology, site of disease, extent of epidural disease, extent of metastases elsewhere, and neurologic status. Treatment recommendations must weigh the risk-benefit profile of external beam radiation therapy (EBRT) for the particular individual's circumstance, including neurologic status, performance status, extent of spinal disease, stability of the spine, extra-spinal disease status, and life expectancy. Patients with spinal instability should be evaluated for surgical intervention. Research studies are needed that evaluate the combination or sequencing of localized therapies with systemic therapies including chemotherapy, hormonal therapy (HT), osteoclast inhibitors (OI), and radiopharmaceuticals. The roles of stereotactic body radiation therapy (SBRT) in the management of spinal oligometastasis, radioresistant spinal metastasis, and previously irradiated but progressive spinal metastasis are emerging, but more research is needed to validate the findings from retrospective studies. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140115/1/jpm.2012.0376.pd

CogState computerized memory tests in patients with brain metastases: Secondary endpoint results of NRG oncology RTOG 0933

Whole brain radiotherapy (WBRT) is associated with memory dysfunction. As part of NRG Oncology RTOG 0933, a phase II study of WBRT for brain metastases that conformally avoided the hippocampal stem cell compartment (HA-WBRT), memory was assessed pre-and post-HA-WBRT using both traditional and computerized memory tests. We examined whether the computerized tests yielded similar findings and might serve as possible alternatives for assessment of memory in multi-institution clinical trials. Adult patients with brain metastases received HA-WBRT to 30 Gy in ten fractions and completed Hopkins Verbal Learning Test-Revised (HVLT-R), CogState International Shopping List Test (ISLT) and One Card Learning Test (OCLT), at baseline, 2 and 4 months. Tests’ completion rates were 52–53% at 2 months and 34–42% at 4 months. All baseline correlations between HVLT-R and CogState tests were significant (p B 0.003). At baseline, both CogState tests and one component of HVLT-R differentiated those who were alive at 6 months and those who had died (p B 0.01). At 4 months, mean relative decline was 7.0% for HVLT-R Delayed Recall and 18.0% for ISLT Delayed Recall. OCLT showed an 8.0% increase. A reliable change index found no significant changes from baseline to 2 and 4 months for ISLT Delayed Recall (z =-0.40, p = 0.34; z =-0.68, p = 0.25) or OCLT (z = 0.15, p = 0.56; z = 0.41, p = 0.66). Study findings support the possibility that hippocampal avoidance may be associated with preservation of memory test performance, and that these computerized tests also may be useful and valid memory assessments in multi-institution adult brain tumor trials

ACR Appropriateness Criteria® Non-Spine Bone Metastases

Abstract Bone is one of the most common sites of metastatic spread of malignancy, with possible deleterious effects including pain, hypercalcemia, and pathologic fracture. External beam radiotherapy (EBRT) remains the mainstay for treatment of painful bone metastases. EBRT may be combined with other local therapies like surgery or with systemic treatments like chemotherapy, hormonal therapy, osteoclast inhibitors, or radiopharmaceuticals. EBRT is not commonly recommended for patients with asymptomatic bone metastases unless they are associated with a risk of pathologic fracture. For those who do receive EBRT, appropriate fractionation schemes include 30?Gy in 10 fractions, 24?Gy in 6 fractions, 20?Gy in 5 fractions, or a single 8?Gy fraction. Single fraction treatment maximizes convenience, while fractionated treatment courses are associated with a lower incidence of retreatment. The appropriate postoperative dose fractionation following surgical stabilization is uncertain. Reirradiation with EBRT may be safe and provide pain relief, though retreatment might create side effect risks which warrant its use as part of a clinical trial. All patients with bone metastases should be considered for concurrent management by a palliative care team, with patients whose life expectancy is less than six months appropriate for hospice evaluation. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98458/1/jpm%2E2011%2E0512.pd

Risk factors for late bowel and bladder toxicities in NRG Oncology prostate cancer trials of high-risk patients: A meta-analysis of physician-rated toxicities

Purpose: A meta-analysis of sociodemographic variables and their association with late (\u3e180 days from start of radiation therapy[RT]) bowel, bladder, and clustered bowel and bladder toxicities was conducted in patients with high-risk (clinical stages T2c-T4b or Gleason score 8-10 or prostate-specific antigen level \u3e20) prostate cancer. Methods and materials: Three NRG trials (RTOG 9202, RTOG 9413, and RTOG 9406) that accrued from 1992 to 2000 were used. Late toxicities were measured with the Radiation Therapy Oncology Group Late Radiation Morbidity Scale. After controlling for study, age, Karnofsky Performance Status, and year of accrual, sociodemographic variables were added to the model for each outcome variable of interest in a stepwise fashion using the Fine-Gray regression models with an entry criterion of 0.05. Results: A total of 2432 patients were analyzed of whom most were Caucasian (76%), had a KPS score of 90 to 100 (92%), and received whole-pelvic RT+HT (67%). Of these patients, 13 % and 16% experienced late grade ≥2 bowel and bladder toxicities, respectively, and 2% and 3% experienced late grade ≥3 bowel and bladder toxicities, respectively. Late grade ≥2 clustered bowel and bladder toxicities were seen in approximately 1% of patients and late grade ≥3 clustered toxicities were seen in 2 patients ( Conclusions: Patients with high-risk prostate cancer who receive whole-pelvic RT+LT HT are more likely to have a grade ≥2 bowel toxicity than those who receive prostate-only RT. LT bowel and bladder toxicities were infrequent. Future studies will need to confirm these findings utilizing current radiation technology and patient-reported outcomes

Circulating lymphocyte number has a positive association with tumor response in neoadjuvant chemoradiotherapy for advanced rectal cancer

Although neoadjuvant chemoradiotherapy (CRT) is the standard treatment for advanced rectal cancer (RC), markers to predict the treatment response have not been fully established. In 73 patients with advanced RC who underwent CRT in a neoadjuvant setting, we retrospectively examined the associations between the clinical effects of CRT and blood cell counts before and after CRT. Clinical or pathological complete response (CR) was observed in 10 (14%) cases. The CR rate correlated significantly with the size and the circumferential extent of the tumor. Hemoglobin level, white blood cell (WBC) count and platelet count before CRT did not show a significant difference between CR and non-CR cases. Interestingly, however, lymphocyte ratio in WBC was significantly higher (p = 0.020), while neutrophil ratio tended to be lower (p = 0.099), in CR cases, which was shown to be an independent association by multivariate analysis. When all the blood data obtained in the entire treatment period were evaluated, circulating lymphocyte count was most markedly decreased in the CRT period and gradually recovered by the time of surgery, while the numbers of neutrophils and monocytes were comparatively stable. Moreover, the lymphocyte percentage in samples obtained from CR patients was maintained at a relatively higher level than that from non-CR patients. Since tumor shrinkage is known to be dependent not only on the characteristics of tumor cells but also on various host conditions, our data raise the possibility that a lymphocyte-mediated immune reaction may have a positive role in achieving complete eradication of tumor cells. Maintenance of circulating lymphocyte number may improve the response to CRT in rectal cancer