Search

The article discusses several studies on radiation therapy. It includes "Completion of Adjuvant Radiation Therapy Among Women With Breast Cancer," by T. P. Srokowski et al, "Breast Cancer Surveillance Practices Among Women Previously Treated With Chest Radiation for a Childhood Cancer," by K. C. Oeffinger et al, and "3D Ultrasound Can Contribute to Planning CT to Define the Target for Partial Breast Radiotherapy," by T. S. Berrang et al.

Abstract Background This paper compares the calculated dose to target and normal tissues when using pencil beam (PBC), superposition/convolution (AAA) and Monte Carlo (MC) algorithms for whole breast (WBI) and accelerated partial breast irradiation (APBI) treatment plans. Methods Plans for 10 patients who met all dosimetry constraints on a prospective APBI protocol when using PBC calculations were recomputed with AAA and MC, keeping the monitor units and beam angles fixed. Similar calculations were performed for WBI plans on the same patients. Doses to target and normal tissue volumes were tested for significance using the paired Student's t-test. Results For WBI plans the average dose to target volumes when using PBC calculations was not significantly different than AAA calculations, the average PBC dose to the ipsilateral breast was 10.5% higher than the AAA calculations and the average MC dose to the ipsilateral breast was 11.8% lower than the PBC calculations. For ABPI plans there were no differences in dose to the planning target volume, ipsilateral breast, heart, ipsilateral lung, or contra-lateral lung. Although not significant, the maximum PBC dose to the contra-lateral breast was 1.9% higher than AAA and the PBC dose to the clinical target volume was 2.1% higher than AAA. When WBI technique is switched to APBI, there was significant reduction in dose to the ipsilateral breast when using PBC, a significant reduction in dose to the ipsilateral lung when using AAA, and a significant reduction in dose to the ipsilateral breast and lung and contra-lateral lung when using MC. Conclusions There is very good agreement between PBC, AAA and MC for all target and most normal tissues when treating with APBI and WBI and most of the differences in doses to target and normal tissues are not clinically significant. However, a commonly used dosimetry constraint, as recommended by the ASTRO consensus document for APBI, that no point in the contra-lateral breast volume should receive >3% of the prescribed dose needs to be relaxed to >5%.

While estimation of prognosis for patients with oligometastatic cancer is important to aid in treatment decision making, at present, prognostication tools are lacking. The purpose of this study was to develop predictive models for polymetastatic progression free survival (PPFS) and overall survival (OS), based on patient outcomes on the SABR-5 clinical trial. In the SABR-5 trial (a multi-center, single arm, phase II clinical trial), 381 patients with 1-5 oligometastases or oligoprogressing lesions were treated with stereotactic ablative radiotherapy (SABR). Prostate cancer was the most common histology (32%), followed by colorectal (16%), breast (11%), lung (9%), and renal (9%). Most patients (91%) were treated for 1-2 metastases. PPFS was defined as time from SABR until polymetastatic failure (≥ 6 metastases, or malignant pleural effusion/malignant ascites) or death. We trained separate Cox models for PPFS and OS. An elastic net penalty was used to select from candidate covariates. The model was internally validated using 10-fold cross validation with three repetitions and evaluated using partial likelihood. The proportional hazards and linearity assumptions were tested by examination of scaled Schoenfold Residuals and Martingale Residuals, respectively. After a median follow-up time of 28.0 months (interquartile range [IQR]19.1 – 39.1), median PPFS was 34.3 months (95% confidence interval [CI] 28.8 – 39.9), and median OS was 50.5 months (95% CI 45.2 – 58.9). The resulting PPFS model contained four covariates: primary tumor type (prostate, colorectal, lung, breast, renal, other), ECOG (1-2 vs 0), oligoprogression (yes vs no), number of organs with metastases (single vs multiple). The cross-validated C-Index was 0.66 [95% CI 0.64 – 0.68]. The OS model had five covariates: age (continuous), primary tumor type (prostate, colorectal, lung, breast, renal, other), ECOG (1-2 vs 0), number of organs with metastases (single vs multiple), presence of brain metastasis (yes vs no) and had a corresponding C-Index of 0.67 [95% CI 0.64 – 0.700]. These nomograms can be a useful guiding tool for clinicians in predicting PPFS and OS in patients treated with SABR in oligometastatic or oligoprogressive setting. These models should be externally validated. [ABSTRACT FROM AUTHOR]

Despite advancements in stereotactic ablative radiotherapy (SABR) for non-spine bone metastases (NSBMs), uncertainty remains surrounding target volumes. While expert consensus guidelines recommend a clinical target volume (CTV), patterns of failure analyses are lacking, and larger treatment volumes may be associated with higher toxicity. This study aims to compare local failure, marginal failure, and toxicity in NSBMs treated with versus without a CTV in a population-based cohort. A retrospective review was conducted on all patients in British Columbia treated with SABR for NSBMs on the single-arm phase II SABR-5 trial (November 2016 – July 2020) and on the BC Oligometastases Registry (August 2020 - October 2022). Use of a CTV was optional for both SABR-5 and the Registry. NSBMs were stratified based on CTV use for treatment planning. A total of 158 patients (113 on SABR-5 and 45 on Registry) with 200 NSBMs were included. One hundred fifty-nine (80%) NSBMs were treated with a CTV and 41 (21%) without a CTV. The most common histologies were prostate (60%), breast (17%) and lung cancer (6%), and lesions received 35 Gy in 5 fractions (81%) or 24 Gy in 2 fractions (14%). Rib (34%) and pelvis (47%) were the most common lesion sites. Groups with vs without a CTV did not differ in baseline patient or tumor characteristics. After a median follow-up time of 33.7 months (interquartile range [IQR] = 19.5-48.9), local failure rates did not differ, with 2-year local failure 9.3% (95% confidence interval [CI] = 4.4 – 14.2) in lesions treated with a CTV and 7.6% (95% CI = 0 – 15.8) without a CTV (P = 0.39). Marginal failure, defined as disease recurrence outside of the GTV but within 1 cm of the PTV, occurred in 15 (8%) of lesions and 2-year cumulative incidence did not differ between groups (6.2% [95% CI = 2.3 – 10.1] and 2.6%, [95% CI = 0 – 7.5], respectively [ P = 0.16]). Overall survival (OS) was also similar (2-year OS = 84.6%, 95% CI = 78.1 – 91.1, and 90.3%, 95% CI = 79.9 – 100, respectively; P = 0.64). The most common grade ≥ 2 toxicities were pain (n = 18, 9%) and fracture (n = 8, 4%). There were no grade 4 or 5 toxicities. The 2-year cumulative incidence of grade ≥ 2 toxicity did not differ between groups (14.9%, 95% CI = 3.9-25.9 and 15.6%, 95% CI = 9.9-21.3, respectively; P = 0.78). Due to low number of events, local and marginal failure events were collated for a multivariable regression analysis. On multivariable regression, use of a CTV was not associated with the risk of local-marginal failure (hazard ratio [HR] = 2.41, 95% CI = 0.81 – 7.18, P = 0.11). Extraosseous extension (HR = 2.62, 95% CI = 1.07-6.38, P = 0.035) and lack of receipt of systemic therapy (HR = 3.03, 95% CI = 1.40-6.67, P = 0.005) were associated with higher risk. Use of a CTV was not associated with local or marginal failure or toxicity. Extraosseous extension and lack of receipt of systemic therapy were associated with higher risk of local-marginal failure. This may assist in informing future approaches to treatment planning in this patient population. [ABSTRACT FROM AUTHOR]

Purpose: The recently developed European Society for Radiotherapy and Oncology (ESTRO)/European Organization for Research and Treatment of Cancer (EORTC) oligometastatic disease (OMD) classification has not been validated in terms of its prognostic significance. This study stratified patients from the phase II SABR-5 trial based on ESTRO/EORTC criteria and compared progression-free survival (PFS) and overall survival (OS) to determine the prognostic significance of the classification scheme.Methods and Materials: The SABR-5 trial was a single arm phase II study conducted at the 6 regional cancer centers across British Columbia (BC), Canada, where SABR for oligometastases was only offered on trial. Patients with up to 5 oligometastases (total or not controlled by prior treatment and including induced OMD) underwent SABR to all lesions. Patients were 18 years of age or older, Eastern Cooperative Oncology Group 0 to 2, and life expectancy ≥6 months. PFS and OS were calculated using the Kaplan-Meier method and differences between OMD groups were assessed with log-rank tests. Univariable and multivariable analyses were performed using Cox regression modeling.Results: Between November 2016 and July 2020, 381 patients underwent SABR on trial. Median follow-up was 27 months (interquartile range, 18-36). The most frequent OMD group was de novo OMD (69%), followed by repeat (16%) and induced (13%). OMD groups differed significantly in PFS (P < .001) but not OS (P = .069). The OMD classification was an independent predictor of both PFS (P = .005) and OS (P = .002). Of the 5 classification factors, only chronicity (synchronous, hazard ratio, 0.52; P = .027) and oligoprogression (hazard ratio, 2.05; P = .004) were independently prognostic for OS.Conclusions: In this large prospective cohort, the ESTRO/EORTC classification was an independent predictor of PFS and OS and should be used to identify specific patient groups for clinical trials. In this trial population, the prognostic power is largely attributable to chronicity and oligoprogression. Simplification of the framework may be possible in the future and allow for greater ease of use; however, further data on underrepresented OMD groups and histologies will be required. [ABSTRACT FROM AUTHOR]

While SABR is known for its overall low toxicity and safety, there remains a research gap regarding its combined use with specific systemic therapies. This study aims to evaluate the toxicity of SABR in combination with various systemic therapies. The hypothesis is that certain systemic therapies would significantly increase the risk of Grade 2+ and Grade 3+ radiation therapy-related toxicities when used concurrently with Stereotactic Ablative Radiotherapy (SABR). A secondary analysis of the SABR-5 trial compared grade 2+ and 3+ toxicities associated with SABR until the last follow-up in patients receiving high-risk or non-high-risk systemic therapy at intervals of 3 months, 2 weeks, 1 week, and concurrently with SABR. High-risk systemic therapy was a priori defined, based on previous literature, as drugs that, when given close to SABR, may increase treatment toxicity. This category encompasses cytotoxic chemotherapy drugs, multi-targeted tyrosine kinase inhibitors, cyclin-dependent kinase 4/6 inhibitors, epidermal growth factor receptor inhibitors, anti-vascular endothelial growth factor agents, and anti-cytotoxic T-lymphocyte-associated protein 4 agents. Among the 381 patients, the actuarial rates of grade 2+ and 3+ toxic effects were as follows: for patients not on systemic therapy 3 months prior to SABR (n = 202), the rates were 17.3% and 3.5%, respectively; for patients on non-high-risk systemic therapy concurrent with SABR (n = 102), the rates were 18.6% and 3.9%, respectively; and for patients on high-risk systemic therapy concurrent with SABR (n = 5), the rates were notably higher at 60% and 40%, respectively. On multivariable analysis, concurrent use of high-risk systemic therapy was associated with a higher risk of grade 2+ (OR = 7.15, P = 0.043) or 3+ toxic effects (OR = 13.9, P = 0.015). Significance was not observed when high-risk drugs were used only within 1 week, 2 weeks, or 3 months of SABR, nor with the use of any non-high-risk drugs. A second adverse factor included increased tumor diameter (per 1 cm increment; G2+ OR = 1.25, P < 0.001; G3+ OR = 1.27, P = 0.015). High-risk drugs have demonstrated a potential of increased SABR-related toxicity, warranting caution in their concurrent use with SABR. In contrast, the combination of non-high-risk drugs with SABR may be safe. Ongoing efforts are essential to identify potential risks and uncertainties associated with this therapeutic combination. [ABSTRACT FROM AUTHOR]

To determine polymetastatic recurrence-free survival (PMRFS) in patients with repeat oligometastases (OM) on the SABR-5 trial. SABR-5 is a prospective, multi-center trial that evaluated the safety of stereotactic ablative radiotherapy (SABR) in patients with 1-5 OM or oligoprogressive lesions. On SABR-5, patients were followed post-SABR according to standardized protocols. Patients with repeat extra-cranial OM after metastasis-directed therapy (MDT; SABR, surgery, or thermoablation) to all initial OM (including those treated before enrolment on SABR-5) were identified. Exclusion criteria included history of multiple primary malignancies and incomplete re-staging. PMRFS was defined as time from presentation of repeat oligometastases to death or presentation of 6 or more progressing metastases, leptomeningeal metastases, lymphangitic carcinomatosis, malignant ascites, or malignant pleural effusion. PMRFS, overall survival (OS), and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Seventy-six patients with repeat OM were included, of which 44 (58%) received second MDT to all OM. The most common histology in patients who received second MDT was colorectal cancer (10/44 [23%]) and in those who did not was prostate cancer (17/32 [53%]). Patients who did vs. did not receive second MDT had fewer metastases at repeat OM (mean 1.3 vs 2.2; p<0.001) and no difference in time between initial OM and repeat OM (16 vs. 17 months; p = 0.74). For patients who received second MDT, median follow-up from presentation of repeat OM was 2.6 years. Median PFS after first and second MDT were 15 months (95% CI 11-18) and 11 months (95% CI 7-17), respectively. At last follow-up, 22/44 patients (50%) were alive without polymetastatic recurrence. 3-year PMRFS and OS from presentation of repeat OM were 51% (95% CI 33-66%) and 66% (95% CI 47-79%), respectively. Patients presenting with repeat OM after MDT may still have favorable 3-year PMRFS and OS, which may justify exploring aggressive local treatments in this subpopulation. Further randomized trials in this space are needed. [ABSTRACT FROM AUTHOR]

Despite increasing utilization of stereotactic ablative radiotherapy (SABR), there is a lack of large population-based outcomes data. This study was designed to examine, as the primary end point, side effects and quality of life, which were reported elsewhere. This analysis focuses on overall survival as a secondary endpoint. From November 2016 to July 2020, 401 patients across 6 regional cancer centers in British Columbia, Canada were screened for eligibility in this single arm, phase II trial of SABR in patients with 5 or fewer oligometastatic or oligo-progressive lesions. During this time period, such patients were eligible for SABR only on trial. Of those screened, 385 patients were enrolled, with 381 completing SABR. This analysis was by intention to treat. The median follow up was 26.7 months (range 0-57 months). 68% of the patients were male, the mean age was 68 years old (SD 11 years, range 30-97 years). Median Charlson Comorbidity Index (CCI) was 9 (range 6-15). 60% had ECOG 0, 36% ECOG 1, and 4% ECOG 2. Prostate cancer was the most common histology (32%), followed by colorectal (16%), breast (11%), lung (9%), renal (9%), and others (22%). SABR was given to 1 site in 69% of patients, 2 sites for 22%, 3 sites for 7%, and 4-5 sites for 3%. The most common sites treated with SABR were lung (35%), non-spine bone (25%), spine (16%), lymph node (14%), liver (5%), adrenal (3%), and others (3%). 20% had synchronous disease, and 16% had oligoprogressive disease. Median survival was not reached. At 2 years, the overall survival was 79.8% (75.5-84.1%), and at 4 years, 58.0% (49.6-66.4%). In univariate analysis, age (p=0.023), ECOG (p<0.001), decline in ECOG 6 months before SABR (p=0.001), systemic therapy use after SABR (p=0.001), histology (p<0.001), Synchronous disease (p=0.050), and disease-free interval > 18 months (p<0.001) were significant predictors for overall survival. CCI (p=0.054), gender, oligometastatic disease, and number of lesions treated with SABR were not significant. Multi-variate analysis showed histology (Breast, ref; Lung, HR 9.91 (2.21-44.48), p=0.003; Colorectal, HR 5.09 (1.12-23.09), p=0.035; Renal, HR 5.20 (1.09-24.82), p=0.039; Prostate, p>0.05; Others HR 8.97 (2.07-38.77), p=0.003), ECOG (ECOG 1 vs 0, HR 1.69 (1.10-2.60), p=0.017; ECOG 2 vs 0, HR 3.00 (1.24-7.24), p=0.015), synchronous disease (HR 0.48 (0.27-0.85), p=0.012), and disease-free interval >18 months (HR 2.36 (1.52-3.66), p<0.001) predicted overall survival. Sensitivity analysis of only the patients who completed SABR showed similar results. Analyzing oligometastatic disease only, synchronous disease was not a significant predictor in univariate and multivariate analysis. The 2 years overall survival (80%) was similar to another population-based study in the UK by Chalkidou et al. We recommend continuing to stratify by favorable histology, performance status, and disease-free interval in ongoing randomized phase III trials on the efficacy of SABR. [ABSTRACT FROM AUTHOR]

A subset of patients with oligometastatic cancer experience early widespread cancer dissemination and do not benefit from metastasis-directed therapy such as stereotactic ablative radiotherapy (SABR). This study aimed to identify factors associated with early polymetastatic relapse (PMR). The SABR-5 trial was a single arm phase II study conducted at all 6 regional cancer centers across British Columbia. SABR for oligometastases was only offered on trial. Patients with up to 5 oligometastatic lesions (total, progressing or induced) received SABR to all lesions. Patients were 18 years of age or older, ECOG 0-2 and life expectancy ≥ 6 months. This secondary analysis evaluated factors associated with early PMR, defined as disease recurrence within 6 months of SABR which is not amenable to further local treatment. Univariable and multivariable analyses were performed using binary logistic regression. The Kaplan Meier method and log-rank tests assessed PMR-free survival and differences between risk groups, respectively. Between November 2016 and July 2020, 381 patients underwent treatment on SABR-5. Prostate was the most frequent primary tumor histology (32%), followed by colorectal (17%) and breast (11%). Most patients (69%) underwent SABR to one metastasis and only 10% received SABR to 3 or more lesions. Oligoprogression represented 16% of cases. A total of 16% of patients experienced PMR. Worse performance status (ECOG 1-2 vs 0; HR=2.01, p=0.018), non-prostate/breast histology (HR 3.64, p<0.001) and oligoprogression (HR=3.84, p<0.001) were independent predictors for early PMR. Risk groups were identified with median PMR-free survival ranging from 5 months to not yet reached at the time of analysis. Rates of 3-year OS were 0%, 53% (SE=5%), 77% (SE=4%) and 93% (SE=3%) in groups 1-4, respectively (p<0.001). Four distinct risk groups for early PMR are identified, which differ significantly in PMR-free survival and overall survival. The group with all three risk factors had a median PMR-free survival of 5 months and may not benefit from local ablative therapy alone. This model should be externally validated with data from other prospective trials. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): After the publication of the landmark SABR-COMET trial, concerns were raised over toxicity of SABR for oligometastases. This population-based study was designed as a bridge from phase II to phase III trials, while assessing the toxicity profile of SABR in a larger cohort from a provincial cancer program.Materials/methods: From November 2016 to July 2020, 399 patients were enrolled in this single arm, phase II trial of SABR in patients with oligometastatic or oligo-progressive disease. During this period, patients were only eligible for SABR in these settings on trial within our province, and therefore this analysis is population-based, with resultant minimal selection bias in comparison to previously published SABR series. The primary endpoint was toxicity and we hypothesized grade 4 toxicity < 5%. Grade 2 or higher toxicities were prospectively collected, and were rated as unrelated, unlikely, possibly, probably, or definitely related to SABR. Toxicities rated as possibly, probably, or definitely related to SABR were analyzed in this study. The radiotherapy details are previously published in the protocol; because of previously published high grade toxicity in this setting, all cases underwent individual peer review and organs at risk were prioritized over the planning target volumes.Results: The mean age was 68 years (SD 10.9, range 30-97). The participants were mostly male (69%). The most common histologies were prostate cancer (33%), colorectal cancer (14%), breast cancer (11%), and lung cancer (9%). The number of SABR treated sites were one (69%), two (22%), and three or more (9%). The most common sites of SABR were lung (33%), non-spine bone (28%), spine (14%), lymph nodes (13%), liver (5%) and adrenal (3%). Grade 2, 3, and 4 toxicity cumulative incidences were 11.4%, 4.6%, and 0.5%, respectively. There were no grade 5 toxicities. Grade 2 or higher specific toxicity included 4.8% pain, 1.3% pneumonitis, and 0.8% neuropathy. There were no reported gastrointestinal fistula, perforation, or hemorrhage. Cumulative incidence and prevalence of toxicity at 1 & 3 years will be updated and presented.Conclusion: The incidence of grade 2+ SABR toxicity on this population-based study was 16.5%, which is lower than that reported on SABR-COMET (29%). Importantly, there were no grade 5 toxicities attributed to SABR in this study to date. Severe (grade 3 or higher) toxicities were uncommon (5.0%). These results are encouraging that, in a population-based program with rigorous peer review quality assurance, SABR treatment for oligometastases has acceptable rates of toxicity. This supports further enrollment in randomized phase III trials. [ABSTRACT FROM AUTHOR]