R. Gabriel Boldt

Radiographic changes after lung stereotactic ablative radiotherapy (SABR) - Can we distinguish recurrence from fibrosis? A systematic review of the literature

BACKGROUND Changes in lung density on computed tomography (CT) are common after stereotactic ablative radiotherapy (SABR) and can confound the early detection of recurrence. We performed a systematic review to describe post-SABR findings on computed tomography (CT) and positron-emission tomography (PET), identify imaging characteristics that predict recurrence and propose a follow-up imaging algorithm. METHODS A systematic review was conducted of studies providing detailed radiologic descriptions of anatomic and metabolic lung changes after SABR. Our search returned 824 studies; 26 met our inclusion criteria. Data are presented according to PRISMA guidelines. RESULTS Acute changes post-SABR predominantly appear as consolidation or ground glass opacities. Late changes often demonstrate a modified conventional pattern of fibrosis, evolving beyond 2years after treatment. Several CT features, including an enlarging opacity, correlate with recurrence. Although PET SUVmax may rise immediately post-SABR, an SUVmax⩾5 carries a high predictive value of recurrence. CONCLUSIONS CT density changes are common post-SABR. The available evidence suggests that recurrent disease should be suspected if high-risk CT changes are seen with SUVmax⩾5 on PET. Further studies are needed to validate the predictive values of such metrics, and for advanced analysis of CT changes to allow early detection of potentially curable local recurrence.

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.

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.

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.

252: Are we Helping Cancer Patients Quit Smoking using Smoking Cessation Programs? A Systematic Review and Meta-Synthesis of the Literature

Purpose: Although cigarette smoking contributes to approximately one third of cancer diagnoses, the effects of smoking on patient outcomes after a diagnosis of cancer are less clear. The purpose of this study was to evaluate the impact of the Smoking Cessation Program at our institution over a 12month period, and to perform a meta-synthesis of the literature on the effects of smoking on cancer patient outcomes. Methods and Materials: The Smoking Cessation Program at our institution was launched in March 2014. All new cancer patients are screened for tobacco usage. Smokers are counselled regarding cessation benefits and offered referral to the program. A Smoking Cessation Champion contacts the patient to provide information and counselling. Further follow up is via an interactive voice response telephone system. To assess the success of this program, accrual data at each step of the pathway were collected monthly during the year 2015 and evaluated. To supplement our institutional data, a qualitative review of the literature was performed in Medline by a clinical librarian to assess the impact of smoking on cancer patient outcomes and to review the most effective smoking cessation interventions. Results: Data collected from the Smoking Cessation Program indicate that in 2015, 18% of new patients were current/recent tobacco users. While 93% of smokers were advised of cessation benefits and offered referral, only 16% accepted and only 4% of those enrolled in the automated follow up system. In our review of the literature, 160 studies were identified. After abstract screening and review, several detrimental effects of smoking on cancer patient outcomes were described, including: decreased overall survival, increased risk of disease recurrence/progression, increased side effects, reduced performance status, increased rate of second primary cancers, impaired quality of life, and reduced efficacy of treatment. Proposed mechanisms by which these effects occur include decreased immune response and fibroblast proliferation, genomic instability, resistance to apoptosis, increased angiogenesis, and tissue hypoxia. A meta-analysis of smoking cessation interventions reported that abstinence rates were highest (37% at six months) in patients using a nicotine patch for > 14 weeks with supplementary nicotine replacement therapy (NRT) agents as needed. The addition of behavioural intervention to pharmacological agents doubles abstinence rates. Conclusions: Continued cigarette smoking is detrimental to cancer patient outcomes. The Smoking Cessation Program at our institution has been less successful than those described in the literature. Limitations of the program include challenges in patient access to NRT and minimal follow up. The program is currently undergoing modifications, including initiation of education sessions to engage clinicians in promoting smoking cessation and prescribing NRT.

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.