5-year outcomes after stereotactic ablative body radiotherapy for primary renal cell carcinoma: an individual patient data meta-analysis from IROCK (the International Radiosurgery Consortium of the Kidney).

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is a non-invasive treatment option for primary renal cell carcinoma, for which long-term data are awaited. The primary aim of this study was to report on long-term efficacy and safety of SABR for localised renal cell carcinoma. METHODS: This study was an individual patient data meta-analysis, for which patients undergoing SABR for primary renal cell carcinoma across 12 institutions in five countries (Australia, Canada, Germany, Japan, and the USA) were eligible. Eligible patients had at least 2 years of follow-up, were aged 18 years or older, had any performance status, and had no previous local therapy. Patients with metastatic renal cell carcinoma or upper-tract urothelial carcinoma were excluded. SABR was delivered as a single or multiple fractions of greater than 5 Gy. The primary endpoint was investigator-assessed local failure per the Response Evaluation Criteria in Solid Tumours version 1.1, and was evaluated using cumulative incidence functions. FINDINGS: 190 patients received SABR between March 23, 2007, and Sept 20, 2018. Single-fraction SABR was delivered in 81 (43%) patients and multifraction SABR was delivered in 109 (57%) patients. Median follow-up was 5·0 years (IQR 3·4-6·8). 139 (73%) patients were men, and 51 (27%) were women. Median age was 73·6 years (IQR 66·2-82·0). Median tumour diameter was 4·0 cm (IQR 2·8-4·9). 96 (75%) of 128 patients with available operability details were deemed inoperable by the referring urologist. 56 (29%) of 190 patients had a solitary kidney. Median baseline estimated glomerular filtration rate (eGFR) was 60·0 mL/min per 1·73 m2 (IQR 42·0-76·0) and decreased by 14·2 mL/min per 1·73 m2 (IQR 5·4-22·5) by 5 years post-SABR. Seven (4%) patients required dialysis post-SABR. The cumulative incidence of local failure at 5 years was 5·5% (95% CI 2·8-9·5) overall, with single-fraction SABR yielding fewer local failures than multifraction (Gray's p=0·020). There were no grade 3 toxic effects or treatment-related deaths. One (1%) patient developed an acute grade 4 duodenal ulcer and late grade 4 gastritis. INTERPRETATION: SABR is effective and safe in the long term for patients with primary renal cell carcinoma. Single-fraction SABR might yield less local failure than multifraction, but further evidence from randomised trials is needed to elucidate optimal treatment schedules. These mature data lend further support for renal SABR as a treatment option for patients unwilling or unfit to undergo surgery. FUNDING: None.

An International Consensus on Actions to Improve Lung Cancer Survival: A Modified Delphi Method Among Clinical Experts in the International Cancer Benchmarking Partnership.

BACKGROUND: Research from the International Cancer Benchmarking Partnership (ICBP) demonstrates that international variation in lung cancer survival persists, particularly within early stage disease. There is a lack of international consensus on the critical contributing components to variation in lung cancer outcomes and the steps needed to optimise lung cancer services. These are needed to improve the quality of options for and equitable access to treatment, and ultimately improve survival. METHODS: Semi-structured interviews were conducted with 9 key informants from ICBP countries. An international clinical network representing 6 ICBP countries (Australia, Canada, Denmark, England, Ireland, New Zealand, Northern Ireland, Scotland & Wales) was established to share local clinical insights and examples of best practice. Using a modified Delphi consensus model, network members suggested and rated recommendations to optimise the management of lung cancer. Calls to Action were developed via Delphi voting as the most crucial recommendations, with Good Practice Points included to support their implementation. RESULTS: Five Calls to Action and thirteen Good Practice Points applicable to high income, comparable countries were developed and achieved 100% consensus. Calls to Action include (1) Implement cost-effective, clinically efficacious, and equitable lung cancer screening initiatives; (2) Ensure diagnosis of lung cancer within 30 days of referral; (3) Develop Thoracic Centres of Excellence; (4) Undertake an international audit of lung cancer care; and (5) Recognise improvements in lung cancer care and outcomes as a priority in cancer policy. CONCLUSION: The recommendations presented are the voice of an expert international lung cancer clinical network, and signpost key considerations for policymakers in countries within the ICBP but also in other comparable high-income countries. These define a roadmap to help align and focus efforts in improving outcomes and management of lung cancer patients globally.

Radiofrequency ablation vs radiation therapy vs transarterial chemoembolization vs yttrium 90 for local treatment of liver cancer - a systematic review and network meta-analysis of survival data.

INTRODUCTION: The comparative effectiveness of radiofrequency ablation (RFA), radiation therapy (RT), transarterial chemoembolization (TACE) and transarterial radioembolization with Yttrium-90 (Y90) relative to one another for the treatment of hepatocellular carcinoma (HCC) is unclear. The aim of this systematic review and network meta-analysis is to compare RFA to RT to TACE to Y90 in the treatment of HCC. METHODS: Pubmed, Embase and Cochrane CENTRAL were searched up until April 19, 2021. Observational analyses with propensity score matched (PSM) cohort analyses and randomized controlled trials (RCT) reporting on two or more treatments relative to one another with respect to overall survival (OS) and/or progression free survival (PFS) were included. Survival data were extracted from Kaplan-Meier survival curves, and meta-analyzed using a multivariate network meta-analysis. RESULTS: After exclusions, 24 RCTs or PSM observational studies reporting on 5549 patients were included. While 1-year OS was greater for Y90 than TACE (RR 0.85, 95% CI: 0.72-0.99), all other 1-year OS comparisons across the 4 modalities yielded similar OS, and there were no differences across any modalities in 2-year and 3-year OS. TACE had a modest PFS advantage relative to RFA (RR 0.81, 95% CI: 0.68-0.95) and RT (RR 0.65, 95% CI: 0.51-0.83) at 2 years. CONCLUSION: All modalities assessed resulted in similar OS, which explains the current heterogenous practice patterns. This conclusion may assist in decision making based on administrative and patient costs, and implementation of these modalities. Other factors such as toxicity rate specific to individual patients could not be assessed using network meta-analysis and may also play a role in selection of modality. Further studies, ideally using PSM cohort analyses or RCT study design, reporting on OS, PFS, local control, complete response and toxicity are needed prior to drawing definitive conclusions.

Impact of stereotactic body radiotherapy (SBRT) in oligoprogressive metastatic disease.

PURPOSE: There is increasing interest in using stereotactic body radiation therapy (SBRT) in areas of oligoprogressive metastatic disease (OPD). Our main objective was to investigate the impact of SBRT on overall survival (OS) and the incidence of systemic therapy treatment switches in this population. METHODS: A retrospective institutional review of patients treated with SBRT for OPD was performed. Patients were included if they received SBRT for 1-3 discrete progressing metastases, using a dose of at least 5 Gy per fraction. The study aimed to calculate progression-free survival (PFS), overall survival (OS), local control (LC), and incidence of treatment switch (TS). PFS and OS were calculated using the Kaplan-Meier methodology, while LC and TS were determined using cumulative incidence. RESULTS: Eighty-one patients with a total of 118 lesions were treated with SBRT from July 2014 to November 2020. The Median SBRT dose was 40 (18-60) Gy in 5 (2-8) fractions. Patients had primarily kidney, lung, or breast cancer. Most patients were treated with a tyrosine kinase inhibitor (TKI) (30.9%) or chemotherapy (29.6%) before OPD. The median follow-up post-SBRT was 14 months. Median OS and PFS were 25.1 (95% CI 11.2-39.1) months and 7.8 (95% CI 4.6-10.9) months, respectively. The cumulative incidence of local progression of treated lesions was 5% at 1 year and 7.3% at 2 years. Sixty patients progressed after SBRT and 17 underwent additional SBRT. Thirty-eight patients (47%) changed systemic therapy following SBRT; the cumulative incidence of TS was 28.5% at 6 months, 37.4% at 1 year, and 43.9% at 2 years. CONCLUSIONS: SBRT effectively controls locally progressing lesions but distant progression still occurs frequently. A sizeable number of patients can be salvaged by further SBRT or have minimally progressing diseases that may not warrant an immediate initiation/switch in systemic therapy. Further prospective studies are needed to validate this benefit.

Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial.

BACKGROUND: The oligometastatic paradigm suggests that some patients with a limited number of metastases might be cured if all lesions are eradicated. Evidence from randomised controlled trials to support this paradigm is scarce. We aimed to assess the effect of stereotactic ablative radiotherapy (SABR) on survival, oncological outcomes, toxicity, and quality of life in patients with a controlled primary tumour and one to five oligometastatic lesions. METHODS: This randomised, open-label phase 2 study was done at 10 hospitals in Canada, the Netherlands, Scotland, and Australia. Patients aged 18 or older with a controlled primary tumour and one to five metastatic lesions, Eastern Cooperative Oncology Group score of 0-1, and a life expectancy of at least 6 months were eligible. After stratifying by the number of metastases (1-3 vs 4-5), we randomly assigned patients (1:2) to receive either palliative standard of care treatments alone (control group), or standard of care plus SABR to all metastatic lesions (SABR group), using a computer-generated randomisation list with permuted blocks of nine. Neither patients nor physicians were masked to treatment allocation. The primary endpoint was overall survival. We used a randomised phase 2 screening design with a two-sided α of 0·20 (wherein p<0·20 designates a positive trial). All analyses were intention to treat. This study is registered with ClinicalTrials.gov, number NCT01446744. FINDINGS: 99 patients were randomised between Feb 10, 2012, and Aug 30, 2016. Of 99 patients, 33 (33%) were assigned to the control group and 66 (67%) to the SABR group. Two (3%) patients in the SABR group did not receive allocated treatment and withdrew from the trial; two (6%) patients in the control group also withdrew from the trial. Median follow-up was 25 months (IQR 19-54) in the control group versus 26 months (23-37) in the SABR group. Median overall survival was 28 months (95% CI 19-33) in the control group versus 41 months (26-not reached) in the SABR group (hazard ratio 0·57, 95% CI 0·30-1·10; p=0·090). Adverse events of grade 2 or worse occurred in three (9%) of 33 controls and 19 (29%) of 66 patients in the SABR group (p=0·026), an absolute increase of 20% (95% CI 5-34). Treatment-related deaths occurred in three (4·5%) of 66 patients after SABR, compared with none in the control group. INTERPRETATION: SABR was associated with an improvement in overall survival, meeting the primary endpoint of this trial, but three (4·5%) of 66 patients in the SABR group had treatment-related death. Phase 3 trials are needed to conclusively show an overall survival benefit, and to determine the maximum number of metastatic lesions wherein SABR provides a benefit. FUNDING: Ontario Institute for Cancer Research and London Regional Cancer Program Catalyst Grant.

Stereotactic ablative radiotherapy for the comprehensive treatment of 1-3 Oligometastatic tumors (SABR-COMET-3): study protocol for a randomized phase III trial.

BACKGROUND: A recent randomized phase II trial evaluated stereotactic ablative radiotherapy (SABR) in a group of patients with a small burden of oligometastatic disease (mostly with 1-3 metastatic lesions), and found that SABR was associated with a significant improvement in progression-free survival and a trend to an overall survival benefit, supporting progression to phase III randomized trials. METHODS: Two hundred and ninety-seven patients will be randomized in a 1:2 ratio between the control arm (consisting of standard of care [SOC] palliative-intent treatments), and the SABR arm (consisting of SOC treatment + SABR to all sites of known disease). Randomization will be stratified by two factors: histology (prostate, breast, or renal vs. all others), and disease-free interval (defined as time from diagnosis of primary tumor until first detection of the metastases being treated on this trial; divided as ≤2 vs. > 2 years). The primary endpoint is overall survival, and secondary endpoints include progression-free survival, cost effectiveness, time to development of new metastatic lesions, quality of life (QoL), and toxicity. Translational endpoints include assessment of circulating tumor cells, cell-free DNA, and tumor tissue as prognostic and predictive markers, including assessment of immunological predictors of response and long-term survival. DISCUSSION: This study will provide an assessment of the impact of SABR on survival, QoL, and cost effectiveness to determine if long-term survival can be achieved for selected patients with 1-3 oligometastatic lesions. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03862911. Date of registration: March 5, 2019.

Stereotactic Radiotherapy as a Treatment Option for Renal Tumors in the Solitary Kidney: A Multicenter Analysis from the IROCK.

PURPOSE: Stereotactic ablative radiotherapy is an emerging treatment for renal cell carcinoma. Our study objective was to evaluate this therapy in patients with a solitary kidney, focusing on oncologic and renal function outcomes. MATERIALS AND METHODS: We pooled individual patient data from 9 IROCK (International Radiosurgery Oncology Consortium for Kidney) institutions in Germany, Australia, the United States of America, Canada and Japan. Median followup was 2.6 years. Baseline characteristics and outcomes were compared between the solitary and bilateral kidney cohorts. Predictors of renal function after stereotactic ablative radiotherapy were assessed by logistic regression modeling. RESULTS: A total of 81 patients with a solitary kidney underwent stereotactic ablative radiotherapy. Mean age was 67.3 years and 97.5% of patients had good performance status, including ECOG (Eastern Cooperative Oncology Group) 0-1 or KPS (Karnofsky Performance Status) 70% or greater. Median tumor diameter was 3.7 cm (IQR 2.5-4.3) and 37% of tumors were 4 cm or greater. The 138 patients in the bilateral cohort harbored larger tumors and were older (p <0.001) with a lower baseline estimated glomerular filtration rate (p = 0.024). After stereotactic ablative radiotherapy in the solitary kidney cohort the mean ± SD estimated glomerular filtration rate decrease was -5.8 ± 10.8 ml per minute (-9%). No patient with a solitary kidney required dialysis. After stereotactic ablative radiotherapy a tumor size of 4 cm or greater was associated with an estimated glomerular filtration rate decrease of 15 ml per minute or greater (OR 4.2, p = 0.029). At 2 years the rates of local control, and progression-free, cancer specific and overall survival in the solitary cohort were 98.0%, 77.5%, 98.2% and 81.5%, respectively. There was no significant difference in renal function or oncologic outcomes between the cohorts (p >0.05). CONCLUSIONS: In this analysis of the IROCK database stereotactic ablative radiotherapy in patients with a solitary kidney had an acceptable impact on renal function and achieved excellent oncologic outcomes, similar to those in patients with bilateral kidneys. Thus, stereotactic ablative radiotherapy represents a viable treatment option in patients with renal cell carcinoma in a solitary kidney.

Stereotactic ablative radiotherapy for the comprehensive treatment of 4-10 oligometastatic tumors (SABR-COMET-10): study protocol for a randomized phase III trial.

BACKGROUND: Stereotactic ablative radiotherapy (SABR) has emerged as a new treatment option for patients with oligometastatic disease. SABR delivers precise, high-dose, hypofractionated radiotherapy, and achieves excellent rates of local control for primary tumors or metastases. A recent randomized phase II trial evaluated SABR in a group of patients with a small burden of oligometastatic disease (mostly with 1-3 metastatic lesions), and found that SABR was associated with benefits in progression-free survival and overall survival. The goal of this phase III trial is to assess the impact of SABR in patients with 4-10 metastatic cancer lesions. METHODS: One hundred and fifty-nine patients will be randomized in a 1:2 ratio between the control arm (consisting of standard of care palliative-intent treatments), and the SABR arm (consisting of standard of care treatment + SABR to all sites of known disease). Randomization will be stratified by two factors: histology (Group 1: prostate, breast, or renal; Group 2: all others), and type of pre-specified systemic therapy (Group 1: immunotherapy/targeted; Group 2: cytotoxic; Group 3: observation). SABR is to be completed within 2 weeks, allowing for rapid initiation of systemic therapy. Recommended SABR doses are 20 Gy in 1 fraction, 30 Gy in 3 fractions, or 35 Gy in 5 fractions, chosen to minimize risks of toxicity. The primary endpoint is overall survival, and secondary endpoints include progression-free survival, time to development of new metastatic lesions, quality of life, and toxicity. Translational endpoints include assessment of circulating tumor cells, cell-free DNA, and tumor tissue as prognostic and predictive markers, including assessment of immunological predictors of response and long-term survival. DISCUSSION: This study will provide an assessment of the impact of SABR on clinical outcomes and quality of life, to determine if long-term survival can be achieved for selected patients with 4-10 oligometastatic lesions. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03721341 . Date of registration: October 26, 2018.

Attitudes and beliefs toward the use of stereotactic body radiotherapy in oligometastatic breast cancer: A commentary on a survey of Canadian Medical Oncologists.

Stereotactic body radiotherapy (SBRT) is a highly ablative local therapy which has emerged as part of the treatment paradigm for patients with oligometastatic (OM) breast cancer (defined by 5 or fewer sites). This patient group has demonstrated improved prognosis in some cases and may therefore, benefit from aggressive local treatment. The role of upfront SBRT in newly diagnosed OM breast cancer in addition to systemic therapy is not clear, yet it is being increasingly utilized within the oncology community. The Canadian medical system is an ideal platform in which to investigate SBRT into the OM breast cancer setting, as it is not routinely implemented across centers at this time, as there is potential for robust collaboration between oncologists in the small community to investigate SBRT, and there is limited financial or industry motivation for early SBRT uptake compared with other countries. It is critical therefore to define the optimal patient population and scenarios for which SBRT should be investigated, as well as offered in the interim to Canadian patients. We therefore conducted a survey of Canadian Medical Oncologists, the primary physicians and gatekeepers of patients with OM breast cancer, to characterize their beliefs, opinions, and areas of controversy in the use of SBRT for OM breast cancer.

Pooled analysis of stereotactic ablative radiotherapy for primary renal cell carcinoma: A report from the International Radiosurgery Oncology Consortium for Kidney (IROCK).

BACKGROUND: Stereotactic ablative radiotherapy (SABR) is an emerging therapy for primary renal cell carcinoma. The authors assessed safety, efficacy, and survival in a multi-institutional setting. Outcomes between single-fraction and multifraction SABR were compared. METHODS: Individual patient data sets from 9 International Radiosurgery Oncology Consortium for Kidney institutions across Germany, Australia, the United States, Canada, and Japan were pooled. Toxicities were recorded using Common Terminology Criteria for Adverse Events, version 4.0. Patient, tumor, and treatment characteristics were stratified according to the number of radiotherapy fractions (single vs multiple). Survival outcomes were examined using Kaplan-Meier estimates and Cox proportional-hazards regression. RESULTS: Of 223 patients, 118 received single-fraction SABR, and 105 received multifraction SABR. The mean patient age was 72 years, and 69.5% of patients were men. There were 83 patients with grade 1 and 2 toxicity (35.6%) and 3 with grade 3 and 4 toxicities (1.3%). The rates of local control, cancer-specific survival, and progression-free survival were 97.8%, 95.7%, and 77.4%, respectively, at 2 years; and they were 97.8%, 91.9%, and 65.4%, respectively, at 4 years. On multivariable analysis, tumors with a larger maximum dimension and the receipt of multifraction SABR were associated with poorer progression-free survival (hazard ratio, 1.16 [P < .01] and 1.13 [P = .02], respectively) and poorer cancer-specific survival (hazard ratio, 1.28 [P < .01] and 1.33 [P = .01], respectively). There were no differences in local failure between the single-fraction cohort (n = 1) and the multifraction cohort (n = 2; P = .60). The mean ( ± standard deviation) estimated glomerular filtration rate at baseline was 59.9 ± 21.9 mL per minute, and it decreased by 5.5 ± 13.3 mL per minute (P < .01). CONCLUSIONS: SABR is well tolerated and locally effective for treating patients who have primary renal cell carcinoma and has an acceptable impact on renal function. An interesting observation is that patients who receive single-fraction SABR appear to be less likely to progress distantly or to die of cancer. Cancer 2018;124:934-42. © 2017 American Cancer Society.

Ablative Therapies in Metastatic Breast Cancer: A Systematic Review.

PURPOSE: Patients with oligometastatic breast cancer are being increasingly offered ablative therapies, yet it is unclear which subpopulations may derive long-term benefit. This study sought to explore factors that could define a clinically relevant oligometastatic breast cancer population that benefits from ablative therapies. METHODS: A systematic review using MEDLINE for English language articles published between 1985 and April 2014 was undertaken. Criteria for review included studies that reported overall survival (OS) or progression-free survival (PFS) in breast cancer patients with distant metastases which also: quantified the extent of disease, had metachronous presentation of metastases, and reported on at least 5 patients. RESULTS: Of 59 674 screened studies, 41 studies of 1813 individual patients were identified. All studies were observational cohort studies (level 2B or 4 evidence) and underwent critical review. All outcomes pertaining to OS and PFS were extracted. Extracted data were too heterogeneous to facilitate a meta-analysis. The only factor that suggested worse outcomes was positive margins post-metastasectomy. There was no clear signal for improved outcomes in regards to age, disease extent, disease-free interval, or receptor status. CONCLUSION: Existing evidence does not provide meaningful direction on which metastatic breast cancer patients should have ablation of their residual disease due to heterogeneous reporting of disease factors, patient factors, and outcomes. Thorough demonstration of the absence of high- or moderate-level evidence and the absence of clinical data to guide patient selection suggests that metastatic breast cancer patients being treated with ablative modalities should be placed on clinical trial.

Stereotactic Ablative Radiotherapy for Gynecological Oligometastatic and Oligoprogessive Tumors.

Importance: The role of stereotactic ablative radiotherapy (SABR) for gynecologic malignant tumors has yet to be clearly defined despite recent clinical uptake. Objective: To evaluate the outcomes of SABR in patients with oligometastatic and oligoprogressive gynecologic cancers. Design, Setting, and Participants: In this retrospective pooled analysis, patients with oligometastatic and oligoprogressive gynecologic cancers receiving SABR at 5 institutions from Canada and the US were studied. Data were collected from January 2011 to December 2020, and data were analyzed from January to December 2023. Exposure: Stereotactic ablative radiotherapy. Main Outcomes and Measures: Cumulative incidence of local and distant recurrence, chemotherapy-free survival (CFS), and overall survival (OS) probabilities after SABR were calculated using Kaplan-Meier methods. Univariable and multivariable analysis was conducted using Cox regression methods. Results: A total of 215 patients with 320 lesions meeting criteria were included in the analysis; the median (range) age at primary diagnosis was 59 (23-86) years. The median (range) follow-up from SABR was 18.5 (0.1-124.5) months. The primary site included the endometrium (n = 107), ovary (n = 64), cervix (n = 30), and vulva or vagina (n = 14). Local cumulative incidence of recurrence was 13.7% (95% CI, 9.4-18.9) and 18.5% (95% CI, 13.2-24.5) at 1 and 5 years, respectively. Distant cumulative incidence of recurrence was 48.5% (95% CI, 41.4-55.1) and 73.1% (95% CI, 66.0-79.0) at 1 and 5 years, respectively. OS was 75.7% (95% CI, 69.2-81.1) and 33.1% (95% CI, 25.3-41.1) at 1 and 5 years, respectively. The median CFS was 21.7 months (95% CI, 15.4-29.9). On multivariable analysis, local recurrence was significantly associated with nodal metastasis, lesion size, biologically effective dose, treatment indication, institution, and primary disease type. Distant progression-free survival was associated with nodal targets and lesion size. OS and CFS were significantly associated with lesion size. Conclusions and Relevance: In this study, SABR appeared to have excellent local control with minimal toxic effects in this large patient group, and certain patients may achieve durable distant control and OS as well. It may be possible to delay time to chemotherapy in select patient subtypes and therefore reduce associated toxic effects. Prospective multicenter trials will be critical to establish which characteristics procure the greatest benefit from SABR use and to define the ideal time to implement SABR with other oncologic treatments.

Stereotactic Radiation for Ultra-Central Non-Small Cell Lung Cancer: A Safety and Efficacy Trial (SUNSET).

PURPOSE: The use of stereotactic body radiation therapy for tumors in close proximity to the central mediastinal structures has been associated with a high risk of toxicity. This study (NCT03306680) aimed to determine the maximally tolerated dose of stereotactic body radiation therapy for ultracentral non-small cell lung carcinoma, using a time-to-event continual reassessment methodology. METHODS AND MATERIALS: Patients with T1-3N0M0 (≤6 cm) non-small cell lung carcinoma were eligible. The maximally tolerated dose was defined as the dose of radiation therapy associated with a ≤30% rate of grade (G) 3 to 5 prespecified treatment-related toxicity occurring within 2 years of treatment. The starting dose level was 60 Gy in 8 daily fractions. The dose-maximum hotspot was limited to 120% and within the planning tumor volume; tumors with endobronchial invasion were excluded. This primary analysis occurred 2 years after completion of accrual. RESULTS: Between March 2018 and April 2021, 30 patients were enrolled at 5 institutions. The median age was 73 years (range, 65-87) and 17 (57%) were female. Planning tumor volume was abutting proximal bronchial tree in 19 (63%), esophagus 5 (17%), pulmonary vein 1 (3.3%), and pulmonary artery 14 (47%). All patients received 60 Gy in 8 fractions. The median follow-up was 37 months (range, 8.9-51). Two patients (6.7%) experienced G3-5 adverse events related to treatment: 1 patient with G3 dyspnea and 1 G5 pneumonia. The latter had computed tomography findings consistent with a background of interstitial lung disease. Three-year overall survival was 72.5% (95% CI, 52.3%-85.3%), progression-free survival 66.1% (95% CI, 46.1%-80.2%), local control 89.6% (95% CI, 71.2%-96.5%), regional control 96.4% (95% CI, 77.2%-99.5%), and distant control 85.9% (95% CI, 66.7%-94.5%). Quality-of-life scores declined numerically over time, but the decreases were not clinically or statistically significant. CONCLUSIONS: Sixty Gy in 8 fractions, planned and delivered with only a moderate hotspot, has a favorable adverse event rate within the prespecified acceptability criteria and results in excellent control for ultracentral tumors.

Current and Future Treatment Options in the Management of Stage III NSCLC.

For much of the past two decades, the treatment options for patients with stage III NSCLC were mostly stagnant. In the past 5 years, ongoing innovations have dovetailed alongside advances in biomarker testing, novel therapeutics, precision surgery, and radiotherapy, all of which are leading to an increase in more personalized option for the treatment. This review article will focus on several completed and ongoing initiatives involving treatment of patients with stage III NSCLC. First, it will tackle the progress made in curative treatment of unresectable stage III NSCLC, starting with PACIFIC, and branching out into topics such as concurrent immunotherapy and chemoradiation, intensification of consolidative immunotherapy, dual immunotherapy consolidation, and a reflection on those subpopulations that may not benefit from consolidative immunotherapy. Second, there will be discussion of novel strategies in the setting of resectable stage III disease, most notably neoadjuvant therapy using combined chemoimmunotherapy and immunotherapy alone before surgical resection. Third, it will delve into recent data evaluating adjuvant immunotherapy for resectable stage III NSCLC, including adjuvant targeted therapy (for those harboring driver mutations) and postoperative radiotherapy. Finally, a look to future trials/initiatives will be interspersed throughout the review, to reveal the ongoing efforts being made to continue to improve outcomes in this group of patients.

Contemporary real-world radiotherapy outcomes of unresected locally advanced non-small cell lung cancer.

Background: Radiotherapy (RT) is used as monotherapy in poor performance patients with unresected locally advanced non-small cell lung cancer (LA-NSCLC), but their outcomes are not well-described. As novel therapies are increasingly considered in this space, it is important to understand contemporary outcomes of RT alone. Here, in this retrospective cohort study we analyzed LA-NSCLC outcomes of RT alone in Ontario, Canada, and contrasted them against those of standard of care (SoC) treatment of concurrent chemo-radiotherapy (cCRT). Methods: Ontario provincial databases were searched through the Institute of Clinical Evaluative Sciences (IC/ES) for stage III NSCLC patients diagnosed between 2007 and 2017. Surgical patients were excluded, and all patients that received RT without or with chemotherapy were selected. Patients were divided in groups of RT dose received (<40 Gy, 40-55.9 Gy, and ≥56 Gy) and whether they underwent diagnostic 18F-deoxy-glucose (FDG)-positron emission tomography (PET). Results: Five thousand five hundred and seventy-seven stage III patients that received chest RT without surgery between January 2007 and March 2017 were included in this analysis. Within this group, 39.8% (2,225) received RT alone, 47.4% (2,645) cCRT and 12.6% (707) received sequential chemo-radiotherapy (sCRT). Median OS with RT alone in three dose groups <40/40-55.9/≥56 Gy was 7.2, 8.5 and 13.3 months compared to 16.5, 15.8 and 22 months for cCRT patients. Higher RT dose and PET utilization were independently associated with improved survival in multivariate analysis. Conclusions: Radiation monotherapy remains a widely used treatment modality in LA-NSCLC. RT dose and utilization of FDG-PET imaging are associated with improved survival in this group. These findings help improve clinical decision making and serve as basis for future trials.

Survival in Metastatic Renal Cell Carcinoma Treated With Immunotherapy and Stereotactic Radiation Therapy or Immunotherapy Alone: A National Cancer Database Analysis.

Purpose: Immunotherapy (IO) has significantly improved outcomes in metastatic renal cell carcinoma (mRCC). Preclinical evidence suggests that responses to IO may be potentiated via immunomodulatory effects of stereotactic radiation therapy (SRT). We hypothesized that clinical outcomes from the National Cancer Database (NCDB) would demonstrate improved overall survival (OS) in patients with mRCC receiving IO + SRT versus IO alone. Methods and Materials: Patients with mRCC receiving first-line IO ± SRT were identified from the NCDB. Conventional radiation therapy was allowed in the IO alone cohort. The primary endpoint was OS stratified by the receipt of SRT (IO + SRT vs IO alone). Secondary endpoints included OS stratified by the presence of brain metastases (BM) and timing of SRT (before or after IO). Survival was estimated using Kaplan-Meier methodology and compared via the log-rank test. Results: Of 644 eligible patients, 63 (9.8%) received IO + SRT, and 581 (90.2%) received IO alone. Median follow-up time was 17.7 months (range, 2-24 months). Sites treated with SRT included the brain (71.4%), lung/chest (7.9%), bones (7.9%), spine (6.3%), and other (6.3%). OS was 74.4% versus 65.0% at 1 year and 71.0% versus 59.4% at 2 years for the IO + SRT and IO alone groups, respectively, although this difference did not reach statistical significance (log-rank P = .1077). In patients with BM, however, 1-year OS (73.0% vs 54.7%) and 2-year OS (70.8% vs 51.4%) was significantly higher in those receiving IO + SRT versus IO alone, respectively (pairwise P = .0261). Timing of SRT (before or after IO) did not influence OS (log-rank P = .3185). Conclusions: Patients with BM secondary to mRCC had prolonged OS with the addition of SRT to IO. Factors such as International mRCC Database Consortium risk stratification, oligometastatic tumor burden, SRT dose/fractionation, and utilization of doublet therapy should be considered in future analyses to better identify patients who may benefit from combined IO + SRT. Further prospective studies are warranted.

Overall survival in advanced hepatocellular carcinoma treated with concomitant systemic therapy and stereotactic body radiation therapy or systemic therapy alone.

Introduction: First-line systemic therapy (ST) options for advanced hepatocellular carcinoma (HCC) include tyrosine kinase inhibitors and immunotherapy (IO). Evolving data suggest prolonged overall survival (OS) when ST is combined with stereotactic body radiation therapy (SBRT), although evidence is significantly limited in HCC populations. We hypothesized that advanced HCC patients in the National Cancer Database (NCDB) would have improved OS when receiving ST+SBRT vs ST alone. Methods: Stage III/IV HCC patients diagnosed from 2010-2020 and treated with first-line ST±SBRT were identified from the NCDB. The primary endpoint was OS from date of diagnosis stratified by the receipt of SBRT (ST+SBRT vs ST alone). Survival was estimated using Kaplan-Meier methodology and compared via log-rank. Multivariate analysis (MVA) was performed by Cox regression. Results: Of 10,505 eligible patients with stage III disease, 115 (1.1%) received ST+SBRT and 10,390 (98.9%) received ST alone. Of 9,617 eligible patients with stage IV disease, 127 (1.3%) received ST+SBRT and 9,490 (98.7%) received ST alone. Median follow-up time was 6.8 months. Baseline characteristics were similar between cohorts. Patients with stage III disease receiving ST+SBRT had improved median OS (12.62 months vs 8.38 months) and higher rates of survival at 1-year (53.0% vs 38.7%) and 2-years (27.0% vs 20.7%) compared to those receiving ST alone (log-rank P=0.0054). Similarly, patients with stage IV disease receiving ST+SBRT had improved median OS (11.79 months vs 5.72 months) and higher rates of survival at 1-year (49.6% vs 26.2%) and 2-years (23.6% vs 12.0%) (log-rank P<0.0001). On MVA, receipt of SBRT predicted improved OS (HR=0.748, 95%CI 0.588-0.951; P=0.0178) and receipt of IO trended towards improved OS (HR=0.859, 95%CI 0.735-1.003; P=0.0538). Conclusion: In advanced HCC, patients receiving ST+SBRT had improved OS compared to those receiving ST alone. Prospective clinical trials are warranted to better identify HCC populations which may benefit from combined modality therapy.