Stereotactic vs Hypofractionated Radiotherapy for Inoperable Stage I Non-Small Cell Lung Cancer: The LUSTRE Phase 3 Randomized Clinical Trial.

Importance: Stereotactic body radiotherapy (SBRT) is widely used for stage I medically inoperable non-small cell lung cancer (NSCLC), yet varied results from randomized clinical trials (RCTs) and concerns in treating centrally located tumors persist. Objective: To examine whether SBRT would improve local control (LC) compared with hypofractionated conventional radiotherapy (CRT). Design, Setting, and Participants: This phase 3 RCT was conducted in 16 Canadian centers. Patients with medically inoperable stage I (≤5 cm) NSCLC were randomized 2:1 to SBRT of 48 Gy in 4 fractions (peripheral NSCLC) or 60 Gy in 8 fractions (central NSCLC) vs CRT of 60 Gy in 15 fractions. Data were collected from May 2014 to January 2020, and data were analyzed from July 2022 to July 2023. Interventions: SBRT or CRT. Main Outcomes and Measures: The primary objective was to determine the effectiveness of SBRT compared with CRT based on LC at 3 years. Secondary outcomes included event-free survival, overall survival, and toxic effects. All radiation plans were subject to real-time/final review. Local failures were centrally adjudicated. The study was designed to detect a 3-year LC improvement of SBRT from 75% to 87.5%. The target sample size was 324 patients. Results: Of 233 included patients, 119 (51.1%) were male, and the mean (SD) age was 75.4 (7.7) years; the median (IQR) follow-up was 36.1 (26.4-52.8) months. A total of 154 patients received SBRT and 79 received CRT. The 3-year LC was 87.6% (95% CI, 81.9%-93.4%) for SBRT and 81.2% (95% CI, 71.9%-90.5%) for CRT (hazard ratio [HR], 0.61; 95% CI, 0.31-1.20; P = .15). The HR was 1.02 (95% CI, 0.72-1.45; P = .87) for event-free survival and 1.18 (95% CI, 0.80-1.76; P = .40) for overall survival. Minimal acute toxic effects were observed. Among those randomized to SBRT, late grade 3 or 4 toxic effects occurred in 5 of 45 (11%) with central NSCLC and 2 of 109 (1.8%) with peripheral NSCLC; among those randomized to CRT, in 1 of 19 (5%) with central NSCLC and 1 of 60 (2%) with peripheral NSCLC. One patient who received SBRT for an ultracentral lesion (target overlapping proximal bronchus) experienced a possible treatment-related grade 5 event (hemoptysis). Conclusions and Relevance: This RCT compared lung SBRT with hypofractionated CRT that included central/ultracentral tumors. No difference was detected in LC between groups. Severe toxic effects were limited, including patients with central tumors. The trial provides important prospective data evaluating SBRT; however, further research is necessary to determine if SBRT is more effective than CRT for peripheral and central NSCLC. Trial Registration: ClinicalTrials.gov Identifier: NCT03924869.

Disease control outcomes of stereotactic body radiation therapy or moderate hypo-fractionation for prostate cancer: Real-world experience at two Canadian centers.

BACKGROUND: Advantages of using stereotactic body radiation therapy to treat prostate cancer include short treatment times, decreased costs, and limited toxicity. Randomized trial outcomes comparing 5-fraction stereotactic body radiation therapy to conventionally fractionated radiotherapy or hypo-fractionated radiation therapy are pending. OBJECTIVE: We report the 10-year experience with 5-fraction stereotactic body radiation therapy and hypo-fractionated radiation therapy at two Canadian centers. MATERIAL AND METHODS: Patients with low- or intermediate-risk prostate cancer treated with stereotactic body radiation therapy alone (35-40 Gy in 5 fractions) or hypo-fractionated radiation therapy alone (60-62 Gy in 20 fractions) in the period of July 2010 and June 2020. The biochemical relapse-free survival, PSA nadir, interval time to PSA nadir, time to biochemical recurrence (2 ng/ml above PSA nadir) and overall survival were reviewed. Outcomes between treatment groups were compared after propensity-matching by patient baseline characteristics. Kaplan-Meier curves were used to assess biochemical relapse-free survival and overall survival. RESULTS: We identified 205 and 513 patients with low or intermediate-risk prostate cancer who were treated with stereotactic body radiation therapy or hypo-fractionation, respectively. Intermediate-risk category composed 81% and 95% of the stereotactic body radiation therapy and hypo-fractionated radiation therapy cohorts, respectively. After a median follow up of 58.6 months for the stereotactic body radiation therapy cohort and 45.0 months for the hypo-fractionated cohort, biochemical relapse-free survival and overall survival were not significantly different between treatment groups. The 5-year biochemical relapse-free survival rates were 92.1% and 93.6% and overall survival rates were 96.4% and 95.0% for the stereotactic body radiation therapy and hypo-fractionated cohorts, respectively, after propensity-matching. Stereotactic body radiation therapy resulted in a significantly lower PSA nadir (0.18 ng/ml) compared to hypo-fractionated radiation therapy (0.48 ng/ml) in patients with low-risk prostate cancer. Mean time to biochemical recurrence was not different between treatment groups. CONCLUSIONS: Stereotactic body radiation therapy is an effective treatment option for low and intermediate-risk prostate cancer with encouraging biochemical relapse-free survival and overall survival rates comparable with hypo-fractionated radiation therapy.

Evaluation of Volumetric Response Assessment From SABR for Renal Cell Carcinoma (RCC).

PURPOSE: SABR is increasingly used to treat renal cell carcinoma (RCC). However, the optimal method to assess treatment response is unclear. We aimed to quantify changes in both volume and maximum linear size of tumors after SABR and evaluate the utility of the 2 approaches in treatment response assessment. METHODS AND MATERIALS: We retrospectively studied patients with RCC treated with SABR at our institution between 2013 and 2020. All available follow-up computed tomography scans were aligned, and tumors were contoured on all scans. Volume and maximum linear size were measured at each follow-up, relative to these measurements at the time of computed tomography simulation. RESULTS: Twenty-four patients with 25 tumors were included. Median follow-up was 32 months (range, 16-67). Nineteen tumors (76%) had 30% volumetric response at a median time of 7 months after SABR, and 12 tumors (48%) had 30% decrease in maximum linear size at a median time of 16 months. Eighteen tumors (72%) decreased in volume on first follow-up scan and continued to shrink, and 5 tumors (20%) displayed transient growth after SABR (average 24% increase in volume). Compared with T1a tumors, T1b or larger tumors were more likely to have transient growth (8% vs 33%; P = .16) and had higher average relative volume 24 months after SABR (0.47 vs 0.8; P = .022). CONCLUSIONS: Volume measurement results in more pronounced and earlier change compared with linear size measurement when assessing response to SABR. These findings may provide guidance when assessing treatment response for patients with RCC treated with SABR.

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.

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.

Salvage radiotherapy following HiFU: An institutional series and literature review.

INTRODUCTION: Algorithms for the treatment of prostate cancer (PrCa) rely on risk grouping, and those who fall into low (LR) and favourable intermediate risk (FIR) categories have multiple options for treatment. High-intensity focused ultrasound (HiFU) is a local treatment modality that uses ultrasound waves to ablate prostate cancer. In case of treatment failure, optimal salvage modality after HiFU remains unclear. METHODS: Here, we describe a retrospective review of our regional cancer database for men who underwent salvage radiotherapy after failure of HiFU treatment for prostate cancer. Oncologic and toxicity outcomes of the men identified in our database are discussed. RESULTS: We identified 14 men in our regional database who received salvage radiotherapy (70-74 Gy with or without androgen deprivation therapy (ADT) after primary HiFU, in the period of 2009-2017. No cases of any grade 3 or higher toxicity were observed. In our cohort, 50% (7/14) of patients developed secondary biochemical failure at a median follow-up of 54 months post-radiotherapy, with a mean time to biochemical failure of 39 months. We compare our data to other available reports to date consisting mostly of small, non-randomized studies. Our biochemical control rates are noticeably lower compared with those reported by other studies but our length of follow-up is longer, compared with other studies. CONCLUSION: The available data to date suggest that salvage radiotherapy after HiFU failure is well-tolerated albeit with only modest efficacy.

To prescribe or not to prescribe? Perceptions of radiation therapists prescribing medications for common radiation therapy side effects.

BACKGROUND: During radiation therapy treatments patients may require medications to manage radiation toxicities. Since patients are assessed daily by Radiation Therapists (RTs) it would be optimal and timely for patients to receive medication prescriptions for relief of common radiation side effects from the RTs. OBJECTIVES: The purpose of this study was to determine the perceptions that RTs and Radiation Oncologists (ROs) have of frontline treatment RTs prescribing medications to patients for treatment-related side effects. METHODS: A qualitative and quantitative survey consisting of twenty-five questions on a five-point Likert scale, one open-ended question, and three demographic questions was designed. While the survey sought to examine the perceptions that RTs and ROs have of RTs prescribing medications, the survey also proposed eight different medications that RTs could potentially prescribe. The medications that were proposed are commonly prescribed to radiation therapy patients and included anti-emetic, topical anti-bacterial, hydrocortisone cream, topical anaesthetic, anti-diarrheal, anti-spasmodic, urinary analgesic and anti-fungal medications. After the survey was approved by the Research Ethics Board, RTs and ROs at a large, academic cancer centre were invited to complete the survey. To analyze the survey results, several statistical tests were performed separately for the RTs' surveys and the ROs' surveys. The chi-squared test was used to determine if the sample RT and RO populations were representative of the actual RT and RO populations (p < 0.05). Additionally, the Sign test for medians was used to analyze statistically the responses to the Likert scale questions (p < 0.05), while the Kruskal-Wallis test was used to compare the responses to the Likert scale questions across the demographic groups identified in the demographic questions (p < 0.05). RESULTS: The response rate was 34% (31/90) for the RT population and 42% (10/24) for the RO population. The statistical analysis of the RT population's surveys showed that the majority of the RTs shared positive perceptions towards having RTs prescribe medications, while some respondents highlighted negative perceptions in the open-ended qualitative question. The majority of the RTs agreed that RTs should prescribe five of the eight proposed medications, excluding anti-spasmodic, urinary analgesic, and anti-fungal medications. In contrast to the RTs, there was no statistically significant consensus from the ROs on RTs prescribing medications. Furthermore, the ROs had varying opinions on RTs prescribing the eight proposed medications. CONCLUSIONS: Although the sample size in this study was small, the results from the RT population's surveys supported RTs prescribing medications. The positive results from the RTs and the equivocal response from the ROs suggest that future research should be conducted. Additionally, a future pilot study could be implemented where RTs prescribe one or more of the five medications that were supported to prescribe by the RTs. By having RTs prescribe medications to patients in a pilot study, the effectiveness on patient care could be measured.

Stereotactic body radiotherapy for osseous low alpha-beta resistant metastases for pain relief-SOLAR-P.

BACKGROUND: Stereotactic Body Radiotherapy (SBRT) has shown effectiveness in treating bone metastases to alleviate pain. The benefit of SBRT may be further harnessed especially when radiating disease from primary malignancies with low alpha-beta ratios in order to maximize the magnitude and durability of pain relief. However, such an approach has not been studied in a prospective trial. We look to assess single-fraction SBRT for painful non-spinal bone metastases from radioresistant primaries. METHODS: Forty patients will be enrolled on an open label, phase II single arm trial to receive a single fraction of SBRT (15-20 Gray) to all sites of bone metastases requiring treatment for pain relief. Eligible patients will include those with primary malignancies consisting of prostate cancer, breast cancer, renal cell carcinoma, or melanoma. The primary endpoint is pain response at 3 months post-treatment using the Brief Pain Inventory. Secondary endpoints include pain response at 1 month and 6 months post-treatment, toxicity, patient-reported quality of life, re-irradiation or salvage surgery, and local control. DISCUSSION: This study will evaluate the efficacy of single-fraction SBRT on painful bone metastases from primary cancers with low alpha-beta ratios. These data will be valuable to promote future randomized trials and support clinical implementation. Trial registration Clinicaltrials.gov, NCT04177056. Date of registration: November 26, 2019. https://clinicaltrials.gov/ct2/show/NCT04177056.

Overall and chemotherapy-free survival following stereotactic body radiation therapy for abdominopelvic oligometastases.

INTRODUCTION: Limited data establish the efficacy and safety of SBRT in the abdominopelvic (AP) space, where SBRT delivery is challenging due to the proximity of radiosensitive luminal gastrointestinal (GI) organs. The aim of this study was to assess clinical outcomes in patients with AP OM treated with SBRT. METHODS: Eligible patients were those with OM (defined as metastases in ≤3 total sites) in the AP space (excluding liver) treated with SBRT. Descriptive statistics and Kaplan-Meier estimates of (LC), progression-free survival (PFS), overall survival (OS) and chemotherapy-free survival (CFS) were performed. RESULTS: Fifty-one patients with 58 AP OM received SBRT between 2011 and 2015. Median follow-up was 21.9 months. All SBRT treatments were delivered in 5 fractions with a median dose of 35 Gy (25-40 Gy). Progression post-SBRT occurred in 38/51 patients (75%), with a median PFS of 4.9 months (95% CI: 2.5-7.5), and 2-year PFS of 29%. Rates of 2-and 4-year LC were 74% and 69%, respectively. Median OS was 42.6 months (95% CI: 31-55). Oligometastatic progression occurred in 21/38 patients, and of those, 48% (10/21) received further SBRT. Resulting 2- and 4-year CFS were 47% and 37%, respectively (median 15.1 months). Nineteen patients (37%) experienced a grade 1 or 2 acute toxicity. One grade 3 (acute) toxicity was observed. No grade 4 or 5 toxicities were detected. CONCLUSIONS: SBRT to AP OM was associated with sustained LC, excellent OS and minimal toxicity. The use of SBRT allowed for prolonged CFS and the salvage of limited-burden distant failures.

A Randomized Phase II Trial of Prostate Boost Irradiation With Stereotactic Body Radiotherapy (SBRT) or Conventional Fractionation (CF) External Beam Radiotherapy (EBRT) in Locally Advanced Prostate Cancer: The PBS Trial (NCT03380806).

Standard therapy for high-risk (HR) prostate cancer (PrCa) involves androgen deprivation therapy (ADT) and pelvic conventional fractionation (CF) external beam radiotherapy (EBRT) followed by boost CF-EBRT treatment to prostate for a total of 78 to 80 Gy in 39 to 40 fractions. This is a long and inconvenient treatment for patients. Brachytherapy boost treatment studies indicate that escalation of biological dose of radiotherapy (RT) can improve outcomes in HR-PrCa. However, brachytherapy is an invasive treatment associated with increased toxicity and requires specialized resources. Stereotactic body radiotherapy (SBRT) is a promising, non-invasive alternative to brachytherapy. However, its impact on patient quality of life (QoL) and RT-associated toxicity has not been investigated in a randomized setting. In this study, we investigate SBRT as a boost treatment, following pelvic CF-EBRT, in patients with HR-PrCa treated with ADT. One hundred patients with locally advanced PrCa will be randomized to receive daily CF-EBRT of 45 to 46 Gy in 23 to 25 fractions followed by either daily CF-EBRT of 32 to 33 Gy in 15 to 16 fractions (control arm) or SBRT boost treatment of 19.5 to 21 Gy in 3 fractions (1 fraction per week) (experimental arm). The primary objective of the PBS trial is early bowel and urinary QoL (expanded prostate index composite [EPIC], up to 6 months after RT). This phase II randomized study (PBS) provides an appropriate setting to investigate effectively the impact of SBRT boost on QoL and toxicity in patients with HR-PrCa, before this modality can be compared against the current standard of care in larger phase III protocols.