Characterizing Surgical and Radiotherapy Outcomes in Non-metastatic High-Risk Prostate Cancer: A Systematic Review and Meta-Analysis.

Background Identifying the optimal management of high-risk non-metastatic prostate cancer (PCa) is an important public health concern, given the large burden of this disease. We performed a meta-analysis of studies comparing PCa-specific mortality (CSM) among men diagnosed with high-risk non-metastatic PCa who were treated with primary radiotherapy (RT) and radical prostatectomy (RP). Methods Medline and Embase were searched for articles between January 1, 2005, and February 11, 2020. After title and abstract screening, two authors independently reviewed full-text articles for inclusion. Data were abstracted, and a modified version of the Newcastle-Ottawa Scale, involving a comprehensive list of confounding variables, was used to assess the risk of bias. Results Fifteen studies involving 131,392 patients were included. No difference in adjusted CSM in RT relative to RP was shown (hazard ratio, 1.02 [95% confidence interval: 0.84, 1.25]). Increased CSM was found in a subgroup analysis comparing external beam radiation therapy (EBRT) with RP (1.35 [1.10, 1.68]), whereas EBRT combined with brachytherapy (BT) versus RP showed lower CSM (0.68 [0.48, 0.95]). All studies demonstrated a high risk of bias as none fully adjusted for all confounding variables. Conclusion We found no difference in CSM between men diagnosed with non-metastatic high-risk PCa and treated with RP or RT; however, this is likely explained by increased CSM in men treated with EBRT and decreased CSM in men treated with EBRT + BT studies relative to RP. High risk of bias in all studies identifies the need for better data collection and confounding control in the PCa research.

Stereotactic ablative radiotherapy in T1-2N0M0 small cell lung cancer: A systematic review and meta-analysis.

OBJECTIVES: Stereotactic ablative radiotherapy (SABR) is used to treat inoperable early-stage, node-negative small cell lung cancer (SCLC). We performed a systematic review and meta-analysis of the literature on SABR for T1-2N0M0 SCLC to summarize outcomes including local control (LC), overall survival (OS), recurrence rates, and toxicity. MATERIALS AND METHODS: This study was conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) and MOOSE (Meta-analysis of Observational Studies in Epidemiology) guidelines. A systematic review of PubMed and EMBASE (inception to April 2021) was conducted. Two authors independently reviewed articles for inclusion and extracted study-level data. Random-effects meta-analysis was conducted using R (version 3.6.2) at a significance threshold of 0.05. RESULTS: Eleven studies were identified in the systematic review and seven (399 patients) were selected for meta-analysis. Inoperability was noted as the indication for SABR in 94% (75-100%) of patients. Median follow-up and tumor size were 19.5 months (11.9-32) and 24 mm (19-29), respectively. Chemotherapy and PCI use rates were 44.1% (95% confidence interval [CI], 27.0-61.9%) and 13.8% (95% CI, 0.4-41.2%), respectively. Local control was 97.3% (95% CI, 92.3-99.8%) at 1 year and 95.7% (95% CI, 74.2-100.0%) at 2 years. Overall survival was 86.3% (95% CI, 74.4-94.9%) at 1 year and 63.7% (95% CI, 45.7-79.9%) at 2 years. Nodal and distant recurrence rates were 17.8% (95% CI, 7.5-31.2%) and 26.9% (95% CI, 7.4-53.0%), respectively. The rates of grade 1, grade 2, and grade 3 toxicity (CTCAE) were 12.6% (95% CI, 6.7-19.9%), 6.7% (95% CI, 3.3-11.2%), and 1.4% (95% CI, 0.0-5.3%), respectively. No grade 4 or 5 events were observed across the studies. CONCLUSION: SABR for inoperable early-stage, node-negative SCLC is locally effective with limited toxicity. Prospective studies are required to further evaluate the role of SABR for patients at higher risk of toxicity with surgery or combined chemoradiation.

Risk of Chronic Opioid Use After Radiation for Head and Neck Cancer: A Systematic Review and Meta-Analysis.

PURPOSE: Opioid addiction is a major public health concern. Chronic opioid use (COU) patterns after radiation for head and neck cancer (HNC) remain poorly understood. The aim of this study was to estimate the prevalence of COU and to identify its risk factors in patients with HNC undergoing curative-intent radiation therapy (RT) or chemoradiotherapy (CRT). METHODS AND MATERIALS: We performed a systematic review and meta-analysis using the PubMed (Medline), EMBASE, and Cochrane Library databases, queried from dates of inception until January 2020. COU was defined as persistent use of opioids ≥ 3 months after treatment completion. Meta-analyses were performed using random effects models. Heterogeneity was assessed using the I2 value. RESULTS: Seven retrospective studies, reporting on 1841 patients, met the inclusion criteria. Median age was 59.4 (range: 56.0-62.0) years with 1343 (72.9%) men and 498 (27.1%) women. Primary tumor locations included oropharynx (n = 891, 48.4%), oral cavity (n = 533, 29.0%), larynx (n = 93, 5.1%), hypopharynx (n = 32, 1.7%), and nasopharynx (n = 29, 1.6%). Eight hundred fifty-four (46.0%) patients had stage I/II and 952 (50.3%) had stage III-IV disease. Three hundred one (16.3%) patients had RT alone, 738 (40.1%) received CRT, and 594 (32.3%) underwent surgery followed by adjuvant RT/CRT. The proportion of patients with HNC who developed COU post-RT/CRT was 40.7% at 3 months (95% confidence interval [CI]: 22.6%-61.7%; I2 = 97.1%) and 15.5% at 6 months (95% CI: 7.3%-29.7%; I2 = 94.3%). Oropharyngeal malignancies had the highest rate of COU based on primary tumor location (46.6%; 95% CI: 30.8%-63.1%; P < .0001). High proportions of COU were found in patients with a history of psychiatric disorder(s) (61.7%), former/current alcohol abuse (53.9%), and opioid requirements before radiation treatment (51.6%; P = .035). CONCLUSIONS: A significant proportion of patients who undergo RT for HNC suffer from COU. High-risk factors for COU include an oropharyngeal primary, history of psychiatric disorder, former/current alcohol abuse, and pre-treatment opioid use. New strategies to mitigate COU are needed.

Do all patients with HER2 positive breast cancer require one year of adjuvant trastuzumab? A systematic review and meta-analysis.

One year of adjuvant trastuzumab is considered the standard treatment for patients with HER2 positive breast cancer. However, a shorter duration of trastuzumab may be associated with reduced costs and side effects. Results from randomized trials with diverse non-inferiority margins comparing one year to a shorter duration of adjuvant trastuzumab are not consistent and have not been systematically reviewed using a non-inferiority meta-analysis approach. We conducted a systematic review and meta-analysis of randomized trials to assess whether a shorter duration of adjuvant trastuzumab was non-inferior to one year of treatment or not. The non-inferiority margin for the meta-analysis was pre-defined as the median of the margins of all the trials included. Data of 11,376 patients from 5 trials were analyzed. Non-inferiority margins in included studies varied from 1.15 to 1.53 with median of 1.29 for HR of DFS. A shorter duration of trastuzumab was non-inferior to one year of therapy for DFS (HR 1.13, 95%CI 1.03-1.24) but inconclusive for OS (HR 1.14, 95%CI 1.00-1.30). In a subgroup analysis for DFS outcome, shorter therapy was non-inferior in patients with ER positive disease (HR 1.10, 95%CI 0.95-1.28) and those with sequential therapy (HR 0.97, 95%CI 0.75-1.27) and when the duration of treatment was 6 months (HR 1.09, 95%CI 0.98-1.22). Although a shorter duration of adjuvant trastuzumab was non-inferior to one year of therapy for DFS in patients with HER2 positive breast cancer based on our HR margin of 1.29, any benefit of a shorter duration comes at a loss of efficacy with an increase in absolute risk up to 3.9% for 5 year DFS. Whether the potential increased risk is clinically acceptable for the benefits of a shorter duration remains debatable.

A Novel Salvage Option for Local Failure in Prostate Cancer, Reirradiation Using External Beam or Stereotactic Radiation Therapy: Systematic Review and Meta-Analysis.

PURPOSE: Reirradiation (re-RT) using external beam radiation therapy (EBRT) is a novel salvage strategy for local failure in prostate cancer. We performed a systematic review describing oncologic and toxicity outcomes for salvage EBRT/stereotactic radiation therapy (SBRT) re-RT. METHODS AND MATERIALS: A International Prospective Register of Systematic Reviews registered (#141466) systematic review, meta-analysis, and meta-regression was conducted using preferred reporting items for systematic reviews and meta-analyses guidelines. PubMed and EMBASE were searched from inception through September 2019. Outcome measures included local control (LC), biochemical relapse free survival (BRFS), and ≥grade 3 genitourinary (GU)/gastrointestinal (GI) toxicity. EBRT and SBRT data were collected separately. Meta-regression explored disease and toxicity outcomes as a function of equivalent dose in 2 Gy fractions (EQD2), length of follow-up, and partial versus whole prostate reirradiation. RESULTS: Nineteen studies representing 13 cohorts were included (428 patients). Weighted mean follow-up was 26.1 months. Median re-RT EQD2 was 77.1 Gy (α/ß = 1.5), with 92% of patients receiving SBRT, 52.1% of patients receiving partial prostate re-RT, and 30.1% of patients receiving androgen deprivation therapy with re-RT. LC was 83.2% (95% confidence interval [CI], 75.5%-90.9%) and BRFS was 59.3% (47.9%-70.7%). Reported late toxicity ≥grade 3 was 3.4% (95% CI, 1.0%-5.8%) for GU and 2.0% (95% CI, 0.1%-4.0%) for GI. Meta-regression found higher LC, BRFS, and reported GU/GI toxicity with increasing EQD2, with partial prostate re-RT associated with less reported GU/GI toxicity and no detriment to LC and BRFS. CONCLUSIONS: Salvage re-RT using EBRT, particularly with SBRT, is an emerging technique to treat isolated local failure of prostate cancer. With short-term follow-up, LC, BRFS, and reported toxicities appear reasonable, although further follow-up is required before definitive statements on late toxicities can be made. Our review is limited by incomplete reporting of androgen deprivation therapy use in the primary literature. Further prospective studies and longer follow-up are needed before considering re-RT as standard practice.

Stereotactic ablative radiotherapy for malignant mediastinal and hilar lymphadenopathy: a systematic review.

BACKGROUND: Stereotactic ablative radiotherapy (SABR) safety and efficacy for mediastinal and hilar lymphadenopathy (MHL) is not yet established, given its potential for toxicity due to the proximity to esophagus and proximal bronchial tree (PBT). This review summarized current reported outcomes of MHL SABR. METHODS: This systematic review, based on the PRISMA guidelines, was performed using MEDLINE® (PubMed®), EMBASE and Cochrane Library databases from inception until December 2018. Studies reporting outcomes from SABR specifically for MHL from all primary malignancies were included. Non- English studies, guidelines, reviews, non-peer reviewed correspondences were excluded. Only the most recent publication and/or largest cohort from a single institution would be included for analysis. RESULTS: From the 222 studies identified, 4 retrospective studies totaling 196 patients were included in the analysis. One study included a small number of patients receiving non-ablative doses of stereotactic radiotherapy (RT). Non-small cell lung cancer (NSCLC) was the most common primary (65%), followed by breast (8%). Median follow-up ranged between 12 and 32 months. Reported dose and fractionation ranged from 21 to 60 Gy in 3-11 fractions, with median BED10 ranged from 46-106 Gy10. Three studies reported local control (LC) rates: study 1, 97% (1-year) and 77% (5-year); study 4, 88% (2-year); and study 2, 69% (6-month) and 66% (16-month). Pooled grade 3-5 toxicity rate according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0 was 6% (n=11). Pooled SABR-related mortality (grade 5 toxicity) rate was 2% (n=4). Three SABR-related deaths from esophageal fistulae (2 to trachea, 1 to mediastinum) were reported, with all 3 having prior RT to the subcarinal nodes. CONCLUSIONS: Our review suggested SABR for MHL to be feasible and effective, though there is a potential for serious toxicity especially in the re-irradiation scenario. Multi-institutional and/or prospective studies will help determine the therapeutic benefit of SABR in this high-risk treatment scenario.

Is lung stereotactic ablative radiotherapy safe after pneumonectomy?-a systematic review.

Patients treated with surgery for lung cancer are at risk of second primary lung cancers (SPLCs), which when localized, may be amenable to radical treatment. Treatment options, however, are limited due to reduced cardiopulmonary reserve and competing mortality risks. The aim of this study was to perform a systematic review of publications examining treatment planning considerations, clinical outcomes, and toxicity rates of stereotactic ablative radiotherapy (SABR) in patients who have previously undergone pneumonectomy. A systematic review of the literature was conducted in accordance with PRISMA guidelines using PubMed and EMBASE from inception to July 2018. Articles were limited to those published in the English language. Non-review articles with patients who received exclusively lung SABR post-pneumonectomy were included. Two reviewers independently performed abstract and full-text review, with discrepancies settled by a third reviewer. Of the 215 articles identified by the initial search, 6 articles comprising 53 patients who received lung SABR post-pneumonectomy met inclusion criteria. The mean age was 68, and most patients were male (73.7%). The mean time to pneumonectomy was 6.5 years. The mean biologically effective dose was 115 Gy, and the most common dose fractionation schemes were 54 Gy in 3 fractions, 48 Gy in 4 fractions, and 50 Gy in 5 fractions. The mean follow-up was 25.4 months. The mean 1-year overall survival and 2-year local control rates were 80.6% and 89.4%. Grade 3 or higher toxicity was reported in 13.2% of patients. SABR appears to be a safe and feasible option for SPLCs in patients with prior pneumonectomy. Multi-institutional and/or prospective studies would be helpful to determine the true risk and appropriateness of SABR in this high-risk patient population.

What is the optimal radiotherapy utilization rate for lung cancer?-a systematic review.

Lung cancer is a major cause of morbidity and mortality globally. Although radiotherapy (RT) may be beneficial in the radical and/or palliative management of many lung cancer patients, it is underutilized worldwide. Population-level development of RT resources requires estimates of optimal radiotherapy utilization rates (ORUR) and actual radiotherapy utilization rate (ARUR). A systematic review of PubMed database for English-language articles from January 2009 to January 2019 was performed. Keywords included utilization, underutilization, demand, epidemiologic, benchmark, RT and cancer. Data abstracted included: study population, diagnosis, stage, year of diagnosis, timing of RT, intent of RT, ARUR, and ORUR. Eligible studies provided ARUR or ORUR for lung cancer, small cell lung cancer (SCLC), or non-small cell lung cancer (NSCLC). Included ARUR were based on at least 1,000 patients who were diagnosed or treated in 2009 or later. Included ORUR were based on evidence review or ARUR in 2009 or later. The initial search strategy yielded 1,627 unique abstracts. After review, 105 articles were determined appropriate for full-text review. From these, a final set of 21 articles met all inclusion criteria. In eight papers, ORUR was estimated. Estimated lifetime ORUR ranged from 61% to 82%. Methods for estimation included the evidence-based guideline model, Malthus model, and criterion-based benchmarking (CBB) model. The majority of estimates (6/8) used the evidence-based guideline model. Fifteen papers provided ARUR on lung cancer, inclusive of SCLC and NSCLC. ARUR within 9 months to 1 year of diagnosis ranged from 39% to 46%. Lifetime ARUR was an estimated 52% in Ontario, Canada. Palliative intent ARUR ranged from 12% in Central Poland to 46% in Ontario, Canada. RT is underutilized for lung cancer globally, and there is wide geographical variation in the level of underutilization.

Safety and Effectiveness of Stereotactic Ablative Radiotherapy for Ultra-Central Lung Lesions: A Systematic Review.

INTRODUCTION: The safety and effectiveness of stereotactic ablative radiotherapy (SABR) in patients with ultra-central lung tumors is currently unclear. We performed a systematic review to summarize existing data and identify trends in treatment-related toxicity and local control following SABR in patients with ultra-central lung lesions. METHODS: We performed a systematic review based on the Preferred Reporting Items for Systemic Reviews and Meta-Analyses guidelines using the PubMed and Embase databases. The databases were queried from dates of inception until September 27, 2018. Studies in the English language that reported treatment-related toxicity and local control outcomes post-SABR for patients with ultra-central lung lesions were included. Guidelines, reviews, non-peer reviewed correspondences, studies focused on re-irradiation, and studies with fewer than five patients were excluded. RESULTS: A total of 446 studies were identified, with 10 meeting all criteria for inclusion. The total sample size from the identified studies was 250 ultra-central lung patients and all studies were retrospective in design. Radiotherapy dose and fractionation ranged from 30 to 60 Gy in 3 to 12 fractions, with biologically effective doses (BED10) ranging from 48 to 138 Gy10 (median, 78-103 Gy10). Median treatment-related grade 3 or greater toxicity was 10% (range, 0-50%). Median treatment-related mortality was 5% (range, 0-22%), most commonly from pulmonary hemorrhage (55%). High-risk indicators for SABR-related mortality included gross endobronchial disease, maximum dose to the proximal bronchial tree greater than or equal to 180 Gy3 (BED3, corresponding to 45 Gy in 5 fractions or 55 Gy in 8 fractions), peri-SABR bevacizumab use, and antiplatelet/anticoagulant use. Median 1-year local control rate was 96% (range, 63%-100%) and 2-year local control rate was 92% (range, 57%-100%). CONCLUSIONS: SABR for ultra-central lung lesions appears feasible but there is a potential for severe toxicity in patients receiving high doses to the proximal bronchial tree, those with endobronchial disease, and those receiving bevacizumab or anticoagulants around the time of SABR. Prospective studies are required to establish the optimal doses, volumes, and normal tissue tolerances for SABR in this patient population.

Is the Importance of Heart Dose Overstated in the Treatment of Non-Small Cell Lung Cancer? A Systematic Review of the Literature.

PURPOSE: Some recent studies have suggested a relationship between cardiac dose and mortality in non-small cell lung cancer (NSCLC), but others have reported conflicting data. The goal of this study was to conduct a systematic review and meta-analysis to provide an evidence-based estimate of the relationship between cardiac dose and mortality in these patients. METHODS AND MATERIALS: A systematic review of MEDLINE (PubMed) and Embase databases (inception to January 2018) was performed according to PRISMA guidelines. Studies that evaluated cardiac dosimetric factors in patients with NSCLC and included outcomes of cardiac events, cardiac mortality, and/or overall survival were identified. RESULTS: From 5614 patients across 22 studies, a total of 214 cardiac dosimetric parameters (94 unique) were assessed as possible predictors of cardiac toxicity or death. Assessed predictors included general (eg, mean heart dose [MHD]), threshold-based (eg, heart V5), and anatomic-based (eg, atria, ventricles) dosimetric factors. The most commonly analyzed parameters were MHD, heart V5, and V30. Most studies did not make corrections for multiplicity of testing. For overall survival, V5 was found to be significant on multivariable analysis (MVA) in 1 of 11 studies and V30 in 2 of 12 studies; MHD was not significant in any of 8 studies. For cardiac events, V5 was found to be significant on multivariable analysis in 1 of 2 studies, V30 in 1 of 3 studies, and MHD in 2 of 4 studies. A meta-analysis of the data could not be performed because most negative studies did not report effect estimates. CONCLUSIONS: Consistent heart dose-volume parameters associated with overall survival of patients with NSCLC were not identified. Multiplicity of testing is a major issue and likely inflates the overall risk of type I errors in the literature. Future studies should specify predictors a priori, correct for multiplicity of testing, and report effect estimates for nonsignificant variables.

Stereotactic ablative radiotherapy for early-stage lung cancer following double lung transplantation.

BACKGROUND: Development of primary lung cancer in donor lung post-lung transplantation is very rare, with few described cases. The safety of stereotactic ablative radiotherapy (SABR) for early-stage lung cancer arising from donor lung is unclear. CASE PRESENTATION: Herein, we present a case of a patient with a Stage IB adenocarcinoma arising from donor lung 8 years post-double lung transplantation, which was performed due to advanced emphysema. The patient was ineligible for surgical management due to chronic lung allograft dysfunction, which significantly compromised pulmonary function. Full dose SABR was delivered with curative intent after a discussion with the patient. The patient tolerated the treatment well, with one episode of subacute toxicity that resolved with treatment. There was no evidence of recurrence at 15 months post-treatment and the patient's pulmonary function did not deviate from the pre-SABR baseline. CONCLUSIONS: SABR appears feasible for medically-inoperable early-stage primary lung adenocarcinoma in the setting of previous double-lung transplantation.

Stereotactic Ablative Radiation Therapy Versus Surgery in Early Lung Cancer: A Meta-analysis of Propensity Score Studies.

PURPOSE: As no completed randomized trials of surgery versus stereotactic ablative radiation therapy (SABR) in patients with early-stage non-small cell lung cancer are available, numerous propensity score studies have attempted to mimic the setting of clinical trials using nonrandomized data. We performed a meta-analysis of propensity score studies comparing SABR and surgery. METHODS AND MATERIALS: The MEDLINE and Embase databases were queried up to December 2016. Two authors independently reviewed the records for inclusion and extracted outcome measures. The study was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and MOOSE (Meta-analysis of Observational Studies in Epidemiology) guidelines. The primary meta-analysis and secondary analyses were carried out using R (version 3.3.2) at a significance level of .05. RESULTS: Sixteen studies were included in the meta-analysis. Overall survival favored surgery (hazard ratio for SABR vs surgery, 1.48 [95% confidence interval, 1.26-1.72]; I2 = 80.5%). Lung cancer-specific survival was not significantly different between SABR and surgery (hazard ratio, 1.17 [95% confidence interval, 0.92-1.50]; I2 = 18.6%). On stratification, overall survival favored both lobectomy and sublobar resection over SABR, although lung cancer-specific survival was again not significantly different. On secondary analysis, the lymph node upstaging rate was 15.6% following surgery, with 11.4% of patients receiving chemotherapy. The propensity score-matching caliper distance and first-author specialty were found to be associated with survival endpoints on regression. CONCLUSIONS: For patients with early-stage non-small cell lung cancer who are eligible for either treatment, better overall survival was seen after surgery compared with SABR. However, lung cancer-specific survival was similar for both treatments. Prospective clinical trials are preferred to propensity analyses in evaluating the nature of non-cancer-related death after SABR.

Treatment-Related Toxicity in Patients With Early-Stage Non-Small Cell Lung Cancer and Coexisting Interstitial Lung Disease: A Systematic Review.

PURPOSE: Definitive treatment for patients with early-stage non-small cell lung cancer (ES-NSCLC) is usually well tolerated. Patients with ES-NSCLC and coexisting interstitial lung disease (ILD) are at increased risk of severe treatment-related toxicity after definitive therapy. The main objective of this systematic review is to provide a pooled estimation of treatment-related mortality and ILD-specific toxicity in this population of patients and to identify trends for further study. METHODS AND MATERIALS: The MEDLINE and Embase databases were queried from respective dates of inception to January 2016. Studies that included patients who underwent definitive treatment for ES-NSCLC not combined with other treatments were included. Patients with oligometastases who were treated with aggressive palliation were included if it did not constitute the majority of patients in a specific study. The results were summarized with weighted proportions according to the sample size of individual studies. RESULTS: Overall, 3056 records were reviewed and 50 journal articles were included in the abstraction. The weighted proportion of treatment-related mortality (and ILD-specific toxicity) in primarily medically inoperable patients was as follows: stereotactic ablative radiation therapy (SABR) 15.6% (25%), particle beam therapy 4.3% (18.2%) and radiofrequency ablation (RFA) 8.7% (25%). The data for medically operable patients who underwent surgery were extracted for reference. Treatment-related mortality and ILD-specific toxicity were 2.2% and 12%, respectively, in the surgical population. On analysis of reported SABR dose parameters, V20 ≤ 6.5% and mean lung dose ≤4.5 Gy were found to be metrics associated with reduced mortality. CONCLUSION: A consistently high level of treatment-related mortality and ILD-specific toxicity was observed in primarily medically inoperable patients treated with SABR, particle beam therapy, and RFA. For these patients, curative treatment should be considered in the context of the high toxicity rates and overall poor prognosis. Stringent radiation dosimetric parameters may result in reduced toxicity.

Does Peer Review of Radiation Plans Affect Clinical Care? A Systematic Review of the Literature.

PURPOSE: Peer review is a recommended component of quality assurance in radiation oncology; however, it is resource-intensive and its effect on patient care is not well understood. We conducted a systematic review of the published data to assess the reported clinical impact of peer review on radiation treatment plans. METHODS AND MATERIALS: A systematic review of published English studies was performed in accordance with the PRISMA guidelines using the MEDLINE and EMBASE databases and abstracts published from major radiation oncology scientific meeting proceedings. For inclusion, the studies were required to report the effect of peer review on ≥1 element of treatment planning (eg, target volume or organ-at-risk delineation, dose prescription or dosimetry). RESULTS: The initial search strategy identified 882 potentially eligible studies, with 11 meeting the inclusion criteria for full-text review and final analysis. Across a total of 11,491 patient cases, peer review programs led to modifications in a weighted mean of 10.8% of radiation treatment plans. Five studies differentiated between major and minor changes and reported weighted mean rates of change of 1.8% and 7.3%, respectively. The most common changes were related to target volume delineation (45.2% of changed plans), dose prescription or written directives (24.4%), and non-target volume delineation or normal tissue sparing (7.5%). CONCLUSIONS: Our findings suggest that peer review leads to changes in clinical care in approximately 1 of every 9 cases overall. This is similar to the reported rates of change in peer review studies from other oncology-related specialties, such as radiology and pathology.

Spontaneous Resolution of Chylothorax-Associated Lymphoma Treated with External Beam Radiotherapy: A Case Report and Comprehensive Review of the Literature.

Chylothorax is a rare complication of advanced lymphoma. We present the case of an 80-year-old man diagnosed with B cell lymphoma presenting with a right chylothorax secondary to a large retroperitoneal mass. His disease was not responsive to initial treatment with chemotherapy. Fractionated radiotherapy to a dose of 2,000 cGy in five fractions was delivered to the retroperitoneal mass, and the chylothorax improved significantly within days of initiation of treatment.

A Single Institution Consensus on the Use of Sequential or Concurrent Hormonal Therapy for Breast Cancer Patients Receiving Radiation Therapy.

BACKGROUND AND OBJECTIVES: For hormone-sensitive breast cancers, treatment with breast-conserving surgery, tamoxifen, or aromatase inhibitors, along with adjuvant radiation, is the mainstay of therapy. The ideal timing of hormonal and radiation treatment is not well defined, and there is a significant degree of practice variability between concurrent and sequential treatment regimes. This variability can cause confusion amongst the clinical team resulting in contradictory recommendations, loss of patient trust, and the potential for missed initiation of hormonal therapy. METHODS: To address this question, a systematic review of the literature was conducted and presented to the breast cancer multidisciplinary team at the London Regional Cancer Center. A three-round modified Delphi method was used to obtain a consensus on a series of a priori determined statements. RESULTS: With the currently available evidence, the consensus was that hormonal therapy should be given sequentially after radiation. This will limit potential overlapping adverse effects between hormonal therapy and radiation that may decrease completion of treatment. The sequential approach has not been associated with any harm in clinical outcomes, and there is some suggestion of increased toxicity with concurrent use. However, in patients at high risk of distant recurrence, they felt it would be reasonable to consider concurrent treatment to avoid any delay in therapy. CONCLUSION: The consensus of our institution to utilize a sequential approach will standardize the treatment decisions and reduce the risk of failing to initiate hormonal therapy. Despite the lack of level 1 evidence, the Delphi methodology did provide a high level of confidence for our group to choose the sequential approach. The consensus was developed after a review of the literature revealed that there was no clear superiority of one schedule over the other and evidence that concurrent treatment may increase adverse events.

Evaluation of Health Economics in Radiation Oncology: A Systematic Review.

PURPOSE: Despite the rising costs in radiation oncology, the impact of health economics research on radiation therapy practice analysis patterns is unclear. We performed a systematic review of cost-effectiveness analyses (CEAs) and cost-utility analyses (CUAs) to identify trends in reporting quality in the radiation oncology literature over time. METHODS AND MATERIALS: A systematic review of radiation oncology economic evaluations up to 2014 was performed, using MEDLINE and EMBASE databases. The Consolidated Health Economic Evaluation Reporting Standards guideline informed data abstraction variables including study demographics, economic parameters, and methodological details. Tufts Medical Center CEA registry quality scores provided a basis for qualitative assessment of included studies. Studies were stratified by 3 time periods (1995-2004, 2005-2009, and 2010-2014). The Cochran-Armitage trend test and linear trend test were used to identify trends over time. RESULTS: In total, 102 articles were selected for final review. Most studies were in the context of a model (61%) or clinical trial (28%). Many studies lacked a conflict of interest (COI) statement (67%), a sponsorship statement (48%), a reported study time horizon (35%), and the use of discounting (29%). There was a significant increase over time in the reporting of a COI statement (P<.001), health care payer perspective (P=.019), sensitivity analyses using multivariate (P=.043) or probabilistic methods (P=.011), incremental cost-effectiveness threshold (P<.001), secondary source utility weights (P=.010), and cost effectiveness acceptability curves (P=.049). There was a trend toward improvement in Tuft scores over time (P=.065). CONCLUSIONS: Recent reports demonstrate improved reporting rates in economic evaluations; however, there remains significant room for improvement as reporting rates are still suboptimal. As fiscal pressures rise, we will rely on economic assessments to guide our practice decisions and policies. We recommend improved adherence to published guidelines and further research to determine the clinical implications of our findings.

Quality of Life After Stereotactic Ablative Radiotherapy for Early-Stage Lung Cancer: A Systematic Review.

BACKGROUND: Stereotactic ablative radiotherapy (SABR) has recently become the guideline-recommended therapy for inoperable patients with early-stage non-small-cell lung cancer (ES-NSCLC) and for patients who decline surgery. Patient-reported outcomes should be a key consideration for any treatment modality; however, to our knowledge, a systematic review of the effects of SABR on health-related quality of life (HRQOL) in this patient population is not yet available. MATERIALS AND METHODS: The Embase and MEDLINE databases were queried to obtain journal studies investigating patient-reported HRQOL after SABR for ES-NSCLC. Studies in the English language were included up to August 1, 2015. Relevant data regarding patient characteristics and study outcomes were abstracted and analyzed. RESULTS: Of the 204 potential studies, 9 met all the inclusion criteria and their data were analyzed. All the studies were prospective in design, ranged in date from 2010 to 2015, and involved patients from Europe and North America. The reviewed studies reported few clinically significant changes in HRQOL scores after SABR. Clinically and statistically significant deteriorations in fatigue and dyspnea were individually reported in 2 studies, but these findings were not replicated by other studies. CONCLUSION: Post-treatment HRQOL scores indicate that SABR is an overall well-tolerated modality for patients with ES-NSCLC who either declined or were unfit for surgery. Future clinical trials comparing SABR and surgery would benefit from the inclusion of HRQOL metrics in the study design.

Prognostic Factors for Prostate Cancer Endpoints Following Biochemical Failure: A Review of the Literature.

PURPOSE: In the setting of biochemical failure (BCF) following primary treatment for prostate cancer, additional discrimination between clinically significant and non-clinically significant biochemical recurrence is critical in defining robust surrogate endpoints for prostate cancer and guiding salvage management decisions. We reviewed the literature to determine which prognostic factors are most significant for predicting prostate cancer-specific survival (PCSS), metastases-free survival (MFS), and/or overall survival (OS) after BCF. MATERIALS AND METHODS: A search of PubMed from 1980 to 2013 yielded 999 studies that examined prognostic factors predictive for PCSS, MFS, and/or OS in prostate cancer patients with BCF following primary treatment. Eligibility criteria for inclusion were: 1) examined a prostate cancer population in the setting of BCF without overt clinical relapse following primary treatment with radical prostatectomy or radiotherapy; 2) based analyses on patient parameters obtained prior to the initiation of salvage therapies; and 3) determined clinical prognostic factors that were significant prognostic measures for at least one of three clinically relevant endpoints: OS, PCS, or MFS. RESULTS: Nineteen eligible studies reported on 8,040 patients that experienced BCF from 1981-2013. The initial primary therapy was variable: radical prostatectomy alone (n=8), radiotherapy alone (n=4), radiotherapy/radical prostatectomy ± adjuvant therapy (n=5), and multiple treatment arms (n=2). There was also heterogeneity in which outcomes were assessed: PCSS (n=14), MFS (n=7), and OS (n=5). The prognostic factors most commonly found to be significant on multivariate analyses were PSA doubling time (PSADT), time to biochemical failure (TTBF), pathological Gleason score (pGS), and age.   CONCLUSIONS: Risk stratification in prostate cancer post-BCF is challenging because of limited predictive modeling that can determine which patients will optimally benefit from salvage therapy. Our systematic literature review has identified PSADT, TTBF, pGS, and age as the leading prognostic factors for the prediction of PCSS, MFS, and OS after BCF. We plan to leverage the Canadian ProCaRS database to perform predictive modeling using the putative findings in the present study in order to propose potential evidence-based surrogate endpoints for prostate cancer in the setting of BCF.

Provision of pandemic disease information by health sciences librarians: a multisite comparative case series.

OBJECTIVE: The research provides an understanding of pandemic information needs and informs professional development initiatives for librarians in disaster medicine. METHODS: Utilizing a multisite, comparative case series design, the researchers conducted semi-structured interviews and examined supplementary materials in the form of organizational documents, correspondence, and websites to create a complete picture of each case. The rigor of the case series was ensured through data and investigator triangulation. Interview transcripts were coded using NVivo to identify common themes and points of comparison. RESULTS: Comparison of the four cases revealed a distinct difference between "client-initiated" and "librarian-initiated" provision of pandemic information. Librarian-initiated projects utilized social software to "push" information, whereas client-initiated projects operated within patron-determined parameters to deliver information. Health care administrators were identified as a key audience for pandemic information, and news agencies were utilized as essential information sources. Librarians' skills at evaluating available information proved crucial for selecting best-quality evidence to support administrative decision making. CONCLUSIONS: Qualitative analysis resulted in increased understanding of pandemic information needs and identified best practices for disseminating information during periods of high organizational stress caused by an influx of new cases of an unknown infectious disease.