Cardiac and Pulmonary Dosimetric Parameters in Lung Cancer Patients Undergoing Post-Operative Radiation Therapy in the Real-World Setting

Purpose/Objective(s): The recently published Lung ART trial reported increased rates of cardiac and pulmonary toxicity in the post-operative radiation therapy arm. It remains unknown whether the dosimetric parameters reported in Lung ART are representative of real-world practice. The purpose of this study is to examine heart and lung dose exposure in patients receiving post-operative radiation therapy for non-small cell lung cancer (NSCLC) across a statewide consortium. Materials/Methods: From 2012 to 2020, 377 patients at 27 academic and community centers within the Michigan Radiation Oncology Quality Consortium (MROQC) underwent surgical resection followed by post-operative radiation therapy for non-metastatic NSCLC. Demographic and dosimetric data were prospectively collected for these patients. Rates of 3D-CRT and IMRT use were analyzed. Mean heart dose (MHD), heart V5, heart V35, mean lung dose (MLD), lung V20, target volume and minimum dose to 95% PTV were calculated for these patients and the reported dosimetric parameters were stratified by treatment modality. Results: 51% of patients in this cohort had N2 disease at the time of surgery, 18% had a positive margin. 65.8% of patients were treated with IMRT compared to 32.1% treated with 3D-CRT. Average MHD for all patients was 10.3 Gy, mean Heart V5 was 40.3% and mean heart V35 was 12.6%. Average MLD was 11.2 Gy and mean lung V20 was 18.9%. These dosimetric parameters did not significantly differ based on treatment modality, with MHD and MLD 9.9 Gy and 10.1 Gy, respectively, for patients treated with 3D-CRT compared to 10.6 Gy and 11.8 Gy for patients treated with IMRT. Conclusion: Cardiac and lung dosimetric parameters for patients receiving post-operative radiation therapy for NSCLC are similar to the dosimetric characteristics reported in Lung ART. The mean heart and mean lung doses observed are slightly lower (MHD 10.3 Gy, MLD 11.2 Gy) compared to Lung ART (MHD 13 Gy, MLD 13 Gy), possibly owing to increased use of IMRT. These data support application of Lung ART\u27s findings outside of the clinical trial setting

Changing attitudes towards management of men with locally advanced prostate cancer following radical prostatectomy: A follow-up survey of Australia-based urologists.

INTRODUCTION: This study examined whether there has been change among Australia-based urologists' knowledge, attitudes and beliefs relating to guideline-recommended adjuvant radiotherapy for men with adverse pathologic features following radical prostatectomy since a prior survey in 2012 and investigated associations between attitudes and treatment preferences. METHODS: A nationwide survey of Australia-based urologist members of the Urological Society of Australia and New Zealand. RESULTS: Ninety-six respondents completed the 2015 survey (30% response rate) compared with 157 (45% response rate) in 2012. There was no significant change in awareness of national clinical practice guidelines for the management of prostate cancer. When considering adjuvant against salvage radiotherapy, urologists were significantly less favourable towards adjuvant radiotherapy in 2015 than in 2012 for two of three hypothetical clinical case scenarios with a high 10-year risk of biochemical relapse according to Memorial Sloan Kettering Cancer Center nomograms (P < 0.001 for both cases). In 2015, urologists were less positive overall towards the recommendation for post-operative adjuvant radiotherapy for men with locally advanced prostate cancer than in 2012 (P < 0.001), reflecting a significant change across a number of attitudes and beliefs. Of note, urologists felt other urologists would more likely be critical if they routinely referred the target patient group for radiotherapy in 2015 compared with 2012 (P = 0.007). CONCLUSION: In 2015 Australia-based urologists were less favourable towards adjuvant radiotherapy over watchful waiting for men with high-risk pathologic features post-prostatectomy than in 2012. We could find no new published research that precipitated this change in attitud

Urologists' referral and radiation oncologists' treatment patterns regarding high-risk prostate cancer patients receiving radiotherapy within 6 months after radical prostatectomy: A prospective cohort analysis

Introduction: Previous studies have observed low rates of adjuvant radiotherapy after radical prostatectomy (RP) for high-risk prostate cancer patients. However, it is not clear the extent to which these low rates are driven by urologists' referral and radiation oncologists' treatment patterns. Method: The Clinician-Led Improvement in Cancer Care (CLICC) implementation trial was conducted in nine public hospitals in New South Wales, Australia. Men who underwent RP for prostate cancer during 2013-2015 and had at least one high-risk pathological feature of extracapsular extension, seminal vesicle invasion and/or positive surgical margins were included in these analyses. Outcomes were as follows: (i) referral to a radiation oncologist within 4 months after RP ('referred'); (ii) commencement of radiotherapy within 6 months after RP among those who consulted a radiation oncologist ('radiotherapy after consultation'). Results: Three hundred and twenty-five (30%) of 1071 patients were 'referred', and 74 (61%) of 121 patients received 'radiotherapy after consultation'. Overall, the probability of receiving radiotherapy within 6 months after RP was 15%. The probability of being 'referred' increased according to higher 5-year risk of cancer-recurrence (P < 0.001). Conclusion: Only 30% of patients with high-risk features are referred to a radiation oncologist with the likelihood of referral being influenced by the perceived risk of cancer-recurrence as well as the urologist's institutional/personal preference. When patients are seen by a radiation oncologist, 61% receive radiotherapy within 6 months after RP with the likelihood of receiving radiotherapy not being heavily influenced by increasing risk of recurrence. This suggests many suitable patients would receive radiotherapy if referred and seen by a radiation oncologist

Clinician-led improvement in cancer care (CLICC) - testing a multifaceted implementation strategy to increase evidence-based prostate cancer care: phased randomised controlled trial - study protocol

BACKGROUND: Clinical practice guidelines have been widely developed and disseminated with the aim of improving healthcare processes and patient outcomes but the uptake of evidence-based practice remains haphazard. There is a need to develop effective implementation methods to achieve large-scale adoption of proven innovations and recommended care. Clinical networks are increasingly being viewed as a vehicle through which evidence-based care can be embedded into healthcare systems using a collegial approach to agree on and implement a range of strategies within hospitals. In Australia, the provision of evidence-based care for men with prostate cancer has been identified as a high priority. Clinical audits have shown that fewer than 10% of patients in New South Wales (NSW) Australia at high risk of recurrence after radical prostatectomy receive guideline recommended radiation treatment following surgery. This trial will test a clinical network-based intervention to improve uptake of guideline recommended care for men with high-risk prostate cancer. METHODS/DESIGN: In Phase I, a phased randomised cluster trial will test a multifaceted intervention that harnesses the NSW Agency for Clinical Innovation (ACI) Urology Clinical Network to increase evidence-based care for men with high-risk prostate cancer following surgery. The intervention will be introduced in nine NSW hospitals over 10 months using a stepped wedge design. Outcome data (referral to radiation oncology for discussion of adjuvant radiotherapy in line with guideline recommended care or referral to a clinical trial of adjuvant versus salvage radiotherapy) will be collected through review of patient medical records. In Phase II, mixed methods will be used to identify mechanisms of provider and organisational change. Clinicians' knowledge and attitudes will be assessed through surveys. Process outcome measures will be assessed through document review. Semi-structured interviews will be conducted to elucidate mechanisms of change. DISCUSSION: The study will be one of the first randomised controlled trials to test the effectiveness of clinical networks to lead changes in clinical practice in hospitals treating patients with high-risk cancer. It will additionally provide direction regarding implementation strategies that can be effectively employed to encourage widespread adoption of clinical practice guidelines. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN1261100125191

A multidisciplinary team oriented intervention to increase clinical practice guideline recommended care for patients with high-risk prostate cancer: a stepped wedge cluster randomised implementation trial

Background: This study assessed whether a theoretically conceptualised tailored intervention centred on multidisciplinary teams (MDTs) increased clinician referral behaviours in line with clinical practice guideline recommendations. Methods: Nine hospital Sites in New South Wales (NSW), Australia with a urological MDT and involvement in a state-wide urological clinical network participated in this pragmatic stepped wedge, cluster randomised implementation trial. Intervention strategies included flagging of high-risk patients by pathologists, clinical leadership, education, and audit and feedback of individuals’ and study Sites’ practices. The primary outcome was the proportion of patients referred to radiation oncology within 4 months after prostatectomy. Secondary outcomes were proportion of patients discussed at a MDT meeting within 4 months after surgery; proportion of patients who consulted a radiation oncologist within 6 months; and the proportion who commenced radiotherapy within 6 months. Urologists’ attitudes towards adjuvant radiotherapy were surveyed pre- and post-intervention. A process evaluation measured intervention fidelity, response to intervention components and contextual factors that impacted on implementation and sustainability. Results: Records for 1071 high-risk post-RP patients operated on by 37 urologists were reviewed: 505 control-phase; and 407 intervention-phase. The proportion of patients discussed at a MDT meeting increased from 17% in the controlphase to 59% in the intervention-phase (adjusted RR = 4.32; 95% CI [2.40 to 7.75]; p < 0·001). After adjustment, there was no significant difference in referral to radiation oncology (intervention 32% vs control 30%; adjusted RR = 1.06; 95% CI [0.74 to 1.51]; p = 0.879). Sites with the largest relative increases in the percentage of patients discussed also tended to have greater increases in referral (p = 0·001). In the intervention phase, urologists failed to provide referrals to more than half of patients whom the MDT had recommended for referral (78 of 140; 56%). Conclusions: The intervention resulted in significantly more patients being discussed by a MDT. However, the recommendations from MDTs were not uniformly recorded or followed. Although practice varied markedly between MDTs, the intervention did not result in a significant overall change in referral rates, probably reflecting a lack of change in urologists’ attitudes. Our results suggest that interventions focused on structures and processes that enable health system-level change, rather than those focused on individual-level change, are likely to have the greatest effect

Facility and Individual-Level Factors Contribute to Racial Disparities in Heart Dose Among Breast Radiotherapy Patients

Purpose/Objective(s): Racial disparities in breast cancer presentation (stage/subtype), baseline cardiac risk, and access to care highlight the need to quantify and address predictors of racial variation in heart dose among women who receive radiotherapy (RT). We sought to explore factors that contribute to heart dose, including intrinsic patient factors and facility level factors. Materials/Methods: We queried a statewide consortium database to examine racial differences in mean heart dose among women treated with whole breast RT at 25 institutions. We generated separate models of heart dose based on disease laterality and receipt of conventional (CWBI) versus accelerated whole breast irradiation (AWBI). We included demographic, disease, and treatment characteristics expected to affect heart dose, as well as facility type. We created a model with only patient-level characteristics followed by a multi-level model to account for clustering within facilities. Results: Among 9042 women in the analytic sample, estimated mean heart doses (Gy) were: 1.74 for left-sided AWBI, 1.60 for left-sided CWBI, 0.61 for right-sided AWBI and 0.66 for right-sided CWBI. On patient-level multivariable analysis, race was an independent predictor of higher heart dose for women with left-sided disease: Black patients receiving ABWI or CWBI and Asian patients receiving AWBI had higher heart doses than White women. Higher heart dose was also associated with separation, breast volume, inclusion of internal mammary nodes, use of intensity modulated RT, supine positioning, dose to 50% of the breast volume, treatment at an academic center, decreasing obesity, decreasing comorbidities, absence of deep inhalation breath hold, and earlier treatment year. Multilevel modeling revealed that 22-30% of the variability in heart dose was attributed to patient clustering within facilities. Multilevel models suggest that heart dose is elevated for Black and most Asian (v. White) patients, with average increase between 3-13% and 6-22%, respectively, and statistically significant (p\u3c0.02) depending upon laterality and fractionation. Multilevel modeling uncovered disparities for Black and Asian right-sided AWBI patients that were not observed in patient-level models. Conclusion: Mean heart doses were higher for Black and Asian women in this sample, even when accounting for relevant patient-level factors. Accounting for treatment facility decreased, but did not eliminate this disparity for left-sided disease and uncovered disparities for right-sided disease. These findings suggest that disparities in heart dose may be influenced by patient factors and the facilities at which women obtain care. Further research is needed to clarify whether disparities for Black and Asian women are due to unmeasured, unmodifiable anatomic or clinical factors versus modifiable individual or system-level factors

Use of Chemotherapy in Patients Receiving Hypofractionated Whole-Breast Irradiation: An Analysis within a State-Wide Quality Consortium

Purpose/Objective(s): Randomized clinical trials support the use of hypofractionated whole breast irradiation (H-WBI) in select patients with early stage breast cancer following breast conserving surgery. Patients who received chemotherapy (CHT) are not well represented on these trials. This study investigates whether receiving CHT prior to WBI is associated with increased toxicity or worse cosmetic outcomes. Materials/Methods: We identified 7,014 women in a state-wide radiation oncology quality consortium database who received WBI with a surgical cavity boost between 11/2011 and 8/2018. Toxicity data were available for 6,870 patients. Significant acute toxicity was defined as patient-reported moderate/severe breast pain (≥4/10), physician-reported CTCAE ≥grade 2 breast pain, or the development of moist desquamation between 7 days prior to and 42 days following the completion of radiotherapy. We determined rates of physician-reported fair/poor cosmetic outcome per the Harvard criteria in 2,012 patients who had ≥1 year of follow-up. Rates of significant acute toxicity and fair/poor cosmetic outcome were compared among patients receiving conventionally fractionated treatment (C-WBI) or H-WBI. Multivariable modeling, adjusting for age, race, BMI, breast volume, separation along the central axis, comorbidity index, smoking status, radiation planning technique, breast D50, triple negative breast cancer, pTis disease, treatment at an academic institution, and receipt of CHT, were used to quantify the strength of association, given as an odds ratio [95%CI], between patient or treatment related factors and clinical endpoints. Results: C-WBI and H-WBI most commonly comprised 45-50.4 Gy in 25-28 fractions and 40-42.72 Gy in 15-16 fractions, respectively. A boost of 10-16 Gy in 5-8 fractions and 10 in 4 fractions was most common for C-WBI and H-WBI, respectively. CHT was administered prior to radiation therapy in 1266 (35%) of the 3,628 patients who received C-WBI and in 558 (17%) of the 3,242 patients who received H-WBI. Crude rates of significant acute toxicity were 43% and 40% for patients receiving CHT followed by C-WBI and C-WBI without CHT, respectively, and 29% and 27% for patients receiving CHT followed by H-WBI and H-WBI without CHT, respectively. CHT was not associated with worse acute toxicity for patients receiving C-WBI (OR=0.94 [0.79-1.12], p=0.50) or H-WBI (OR=0.79 [0.63-1.00], p=0.054). CHT was not associated with increased rates of fair/poor cosmetic outcomes at 1 year (OR=1.21 [0.82-1.78], p=0.33), independent of fractionation. Conclusion: In this large, multi-center cohort, rates of significant acute toxicity and fair/poor cosmetic outcomes were not worse in patients receiving chemotherapy prior to whole breast irradiation, compared to patients who did not receive chemotherapy, regardless of fraction size

Factors Associated with Patient-Reported and Physician-Assessed Acute Toxicity after Hypofractionated Breast Radiotherapy, a Report from a Large Multi-Center Cohort Study

Purpose/Objective(s): In 2018 ASTRO published an update to the 2011 evidence-based guideline for the use of hypofractionated whole breast irradiation (HF-WBI), increasing the patient populations for whom expert consensus supports the use of HF-WBI. While individualized decision making is encouraged, this updated guideline has been expanded to support HF-WBI for patients \u3c50 years, receipt of chemotherapy, larger separation distance, and a diagnosis of DCIS. For some of these indications, however, only moderate data exist. Thus, we now assess patient and physician reported toxicity data in a large prospective registry for populations not well represented on the trials and in whom there is less experience with this approach. Materials/Methods: Prospective data were evaluated from 2,083 patients receiving HF-WBI plus boost, treated between 1/1/2016 – 8/31/2018 at 24 academic and community centers participating in a statewide consortium. A composite toxicity endpoint was defined as occurrence of self-reported (4-10 modified brief pain inventory) or physician-assessed moderate or severe breast pain (CTCAE v. 4.0 grade 2-3) when patient report absent, and/or physician-assessed presence of moist desquamation. Logistic regression models were constructed isolating the effect of specific criteria from the 2011 HF-WBI guidelines, specifically age \u3c50 years, separation distance \u3e25cm, chemotherapy use, and DCIS. This was further adjusted for patient BMI, breast volume, race, comorbidity, smoking status, and IMRT. Results: Mean age was 62 years, mean separation was 22cm. Twenty-two percent of patients were treated for DCIS with the remaining 78% treated for invasive cancer; 17% of patients received chemotherapy. Of the 2,083 patients, 376 patients had more than one 2011 guideline discordance (for ex. \u3c50 years with chemotherapy), therefore 1707 patients were included in this analysis. On multivariable analysis, patients age \u3c 50 years were estimated to be 82% more likely to experience toxicity than older patients (OR=1.82, 95% CI: 1.11-2.97, p=0.02). While unadjusted difference on univariate analysis showed increased toxicity with separation \u3e 25 cm, multivariable analysis revealed no significant difference in toxicity for separation \u3e 25 cm(p=0.25), DCIS (p=0.6753), or treatment following chemotherapy p=0.10). Conclusion: Young breast cancer patients may be at increased risk of acute toxicity compared with other patients when receiving HF-WBI. Additional work is needed to determine why patients \u3c50 years, who were notably underrepresented in the prospective trials establishing the safety and efficacy of HF-WBI, may experience increased breast pain and dermatitis. Work is underway in our group to determine if this same increased risk is appreciated for patients \u3c50 years receiving conventionally fractionated radiotherapy

Analysis of the 2017 American Society for Radiation Oncology (ASTRO) Research Portfolio

© 2018 Elsevier Inc. Purpose: Research in radiation oncology (RO) is imperative to support the discovery of new uses of radiation and improvement of current approaches to radiation delivery and to foster the continued evolution of our field. Therefore, in 2016, the American Society of Radiation Oncology performed an evaluation of research grant funding for RO. Methods and Materials: Members of the Society of Chairs of Academic Radiation Oncology Programs (SCAROP) were asked about funded and unfunded grants that were submitted by their departments between the fiscal years 2014 and 2016. Grants were grouped according to broad categories defined by the 2017 American Society of Radiation Oncology Research Agenda. Additionally, active grants in the National Institutes of Health (NIH) Research Portfolio Online Reporting Tools database were collated using RO faculty names. Results: Overall, there were 816 funded (44%) and 1031 unfunded (56%) SCAROP-reported grants. Total grant funding was over $196 million. The US government funded the plurality (42.2$85 million in funding. From the 31 responding SCAROP institutions, there was a 28% average success rate for RO proposals submitted to the NIH during this period. Conclusions: Though RO researchers from responding institutions were relatively successful in obtaining funding, the overall amount awarded remains small. Continued advocacy on behalf of RO is needed, as well as investment to make research careers more attractive areas for emerging faculty