Moderate Hypofractionation Research Articles

Biochemical disease control outcomes of stereotactic body radiation therapy (SBRT) or moderate hypo-fractionation (HFRT) for low- and intermediate-risk prostate cancer (PrCa): Retrospective analysis of 12 years of experience at two Canadian cancer centers.

363 Background: SBRT uses highly conformal radiotherapy to deliver high dose per fraction treatment. Advantages of SBRT include short treatment times, decreased costs and limited toxicity. Randomized trial outcomes of 7-fraction SBRT for low or intermediate PrCa were reported but results of studies that compared 5-fraction SBRT with conventional and HFRT are pending. Here, we reviewed the 12-year experience with SBRT and HFRT at the Juravinski and Walker Family Cancer Centers in Ontario. Methods: We reviewed patients with low or intermittent-risk PrCa treated with SBRT alone or HFRT alone in the period of July 2010 and February 2022. Database search criteria included treatments with SBRT 35-40Gy in 5 fractions and HFRT 60-62Gy in 20 fractions. Overall survival (OS), time to biochemical failure (per Phoenix criteria: i.e., 2ng/mL above PSA nadir) and biochemical failure-free survival (bFFS) were reviewed. Kaplan-Meier curves were used to assess OS and bFFS. Results: We identified 314 patients with low or intermediate-risk PrCa who were treated with SBRT and 258 patients who were treated with HFRT. Intermediate-risk category composed 86.0% and 95.7% of the SBRT and HFRT cohorts. ISUP Grade Group (GG) distributions for the SBRT and HFRT patients were: GG1: 19.4% and 9.3%, GG2: 72.9% and 74.0%, and GG3: 7.6% and 16.7%, respectively. OS rates at 5 years were 96.6% for SBRT vs. 95.8% for HFRT-treated patients. The 5-year bFFS rates for SBRT and HFRT were 92.3% and 90.1%, respectively. The 7-year bFFS rate for the SBRT cohort was 90.2%. Mean time to biochemical failure was 40.4 months after SBRT vs. 35.8 months after HFRT. Conclusions: SBRT is an effective treatment option for low to intermediate-risk PrCa with encouraging OS and bFFS rates comparable with HFRT. Pending randomized trial results will determine whether SBRT is the new standard of care for this population.

Single High-Dose Irradiation-Induced iRhom2 Upregulation Promotes Macrophage Antitumor Activity Through cGAS/STING Signaling

The clinical application of stereotactic body radiation therapy (SBRT) allows a high dose of radiation to be safely delivered to extracranial targets within the body; however, a high dose per fraction (hypofractionation) has opened the radiation oncology field to new questions on a variety of dose-fractionation schedules, especially the immunomodulatory effects of radiation therapy, which can change after various dose-fractionation schedules. We investigated the immunomodulatory effects of different fractionation schedules. We established a subcutaneous tumor model in wild-type C57BL/6J mice and STING (stimulator of interferon genes)-deficient mice. We then compared the tumor control efficacy of 3 different fractionation schedules: 2 Gy×8, 4.5 Gy×3, and 10 Gy×1, which are similar biologically effective doses. We found the fractionation schedule of 10 Gy×1 had a significantly higher antitumor effect, suggesting that a single high dose induced enhanced antitumor immunity compared with conventional fractionation (2 Gy×8) and moderate hypofractionation (4.5 Gy×3). However, in STING-deficient mice, differential tumor control was not observed among the 3 dose-fractionation schedules, suggesting that cGAS (cyclic GMP-AMP synthase)/STING signaling is involved in the antitumor immune effects of single high-dose schedules. Mechanistically, we found that conventional fractionation induced apoptosis; by comparison, a single high dose was more attuned to induced necroptosis, leading to the release of intracellular irradiation-induced double-stranded DNA (dsDNA) due to the loss of plasma membrane integrity, which then activated the dsDNA sensing signaling cGAS/STING in the recruited macrophage. Furthermore, iRhom2, a member of the conserved family of inhibitory rhomboid-like pseudoproteases, was upregulated in infiltrated macrophages in the single high-dose irradiation microenvironment. Therefore, iRhom2 positively regulates STING and directly promotes tumor necrosis factor α secretion. This exacerbates necroptosis of irradiated tumor cells, leading to continuous dsDNA release and enhancement of cGAS/STING signaling antitumor immunity in a positive feedback loop. iRhom2 amplifies antitumor signaling in a positive feedback loop mediated by cGAS/STING signaling and tumor necrosis factor-driven necroptosis after single high-dose radiation.

Moderate hypofractionation in prostate cancer: experience from Regional Hospital ISSSTE, Morelos

Moderate hypofractionation in prostate cancer: experience from Regional Hospital ISSSTE, Morelos

Targeting Education as a Barrier to Implement Hypofractionation: Results of a Country-Wide Training Program

Access to radiation therapy in low- and middle-income countries (LMICs) could be improved with modern hypofractionated radiation therapy schedules, although their adoption remains limited. We aimed to evaluate perceptions regarding hypofractionation and the effect of a dedicated curriculum in an LMIC. We developed a pilot e-learning hypofractionation curriculum focused on breast, prostate, rectal cancer, and high-grade glioma in Colombia. International educators taught 13 weekly, 90-minute sessions. Participants completed pre- and postcurriculum questionnaires regarding hypofractionation attitudes, 1 to 5 Likert-scale self-confidence, and practices for 12 clinical scenarios. Physicians' responses were categorically scored "1" (for hypofractionation or ultrahypofractionation) or "0" (for conventional fractionation). We used the paired t test to measure pre- versus postcurriculum differences in self-confidence and the McNemar test to detect differences in hypofractionation selection. Across 19 cities in Colombia, 147 clinicians enrolled: 61 radiation oncologists, 6 radiation oncology residents, 59 medical physicists, 18 physics residents, and 3 other staff. Among physicians, education was the greatest barrier to select hypofractionation, common in ultrahypofractionation for prostate (77.6%) and breast cancer (74.6%) and less common for moderate hypofractionation of prostate (61.2%) and breast cancer (52.2%). Additional perceived barriers included unfamiliarity with clinic protocols (7%-22%), clinical experience (5%-15%), personal preference (3%-16%), and lack of technology (3%-20%), with variation across different clinical settings. After the curriculum, paired (n=38) physicians' selection of hypofractionation increased across all disease sites (mean aggregate score 6.2/12 vs 8.2/12, P <.001). Self-confidence among paired clinicians (n=87) increased for prostate ultrahypofractionation (+0.45), rectal ultrahypofractionation (+0.43), breast hypofractionation (+0.38), and prostate hypofractionation (+0.23) (P ≤ .03). In an LMIC with a bundled payment system, lack of education and training was a perceived barrier for implementation of hypofractionation and ultrahypofractionation. A targeted e-learning hypofractionation curriculum increased participant confidence and selection of hypofractionated schedules.

Prostate Cancer Treatment-Related Toxicity: Comparison between 3D-Conformal Radiation Therapy (3D-CRT) and Volumetric Modulated Arc Therapy (VMAT) Techniques.

Objective: This paper illustrates the results of a mono-institutional registry trial, aimed to test whether gastrointestinal (GI) and genitourinary (GU) toxicity rates were lower in localized prostate cancer patients treated with image-guided volumetric modulated arc therapy (IG-VMAT) compared to those treated with IG-3D conformal radiation therapy (IG-3DCRT). Materials and Methods: Histologically proven prostate cancer patients with organ-confined disease, treated between October 2008 and September 2014 with moderately hypofractionated radiotherapy, were reviewed. Fiducial markers were placed in the prostate gland by transrectal ultrasound guide. The prescribed total dose was 70 Gy in 28 fractions. The mean and median dose volume constraints for bladder and rectum as well as total volume of treatment were analyzed as potentially prognostic factors influencing toxicity. The Kaplan−Meier method was applied to calculate survival. Results: Overall, 83 consecutive patients were included. Forty-two (50.6%) patients were treated with 3D-CRT and 41 (49.4%) with the VMAT technique. The median follow-up for toxicity was 77.26 months for the whole cohort. The VMAT allowed for a dose reduction to the rectum and bladder for the large majority of the considered parameters; nonetheless, the only parameter correlated with a clinical outcome was a rectal dose limit V66 > 8.5% for late GI toxicity G ≥ 2 (p = 0.045). Rates of G ≥ 2 toxicities were low among the whole cohort of these patients treated with IGRT. The analysis for rectum dose volume histograms (DVHs) showed that a severe (grade ≥ 2) late GI toxicity was related with the rectal dose limit V66 > 8.5% (p = 0.045). Conclusions: This study shows that moderate hypofractionation is feasible and safe in patients with intermediate and high-risk prostate cancer. Daily IGRT may decrease acute and late toxicity to organs at risk and improve clinical benefit and disease control rate, cutting down the risk of PTV geographical missing. The adoption of VMAT allows for promising results in terms of OAR sparing and a reduction in toxicity that, also given the small sample, did not reach statistical significance.

Shorter Radiation Regimens and Treatment Noncompletion Among Patients With Breast and Prostate Cancer in the United States: An Analysis of Racial Disparities in Access and Quality.

Compared with conventional external-beam radiation therapy (cEBRT) for patients with breast cancer (BC) and prostate cancer (PC), shorter radiation regimens may be associated with lower treatment noncompletion rates. We assess disparities in receipt of shorter radiation regimens and treatment noncompletion for BC and PC. The 2004-2017 National Cancer Database was queried for adjuvant cEBRT or hypofractionated EBRT (hEBRT) for nonmetastatic BC; and definitive cEBRT, moderate hypofractionation (mEBRT), or stereotactic body radiotherapy (SBRT) for localized PC. Multivariable logistic regression identified factors associated with treatment noncompletion and receipt of shorter regimens. We identified 170,386 men with PC (median age [interquartile range], 70 [64-75] years; Black, 17.5%; White, 82.5%) and 306,846 women with BC (61 [52-69] years; Black, 12.3%; White, 87.7%). Among patients who received cEBRT for PC, Black men had higher treatment noncompletion rates compared with White (14.1% v 13.0%; odds ratio [95% CI] 1.07 [1.03 to 1.12]; P < .001). In contrast, treatment noncompletion was not disparate with SBRT (Black 1.6% v White 1.3%; 1.20 [0.72 to 2.00], P = .49) or mEBRT (Black 9.0% v White 7.1%; 1.05 [0.72 to 1.54], P = .79). From 2004 to 2017, SBRT (0.07% to 11.8%; 1.32 [1.31 to 1.33]) and mEBRT (0.35% to 9.1%; 1.27 [1.25 to 1.28]) increased (both P < .001); however, Black men were consistently less likely to receive SBRT (7.4% v White, 8.3%; 0.84 [0.79 to 0.89], P < .001). Among women with BC, there were no racial differences in treatment noncompletion; however, hEBRT was associated with lower treatment noncompletion rates (1.0% v cEBRT 2.3%; 0.39 [0.35 to 0.44], P < .001). Although hEBRT for BC increased (0.8% to 35.6%) between 2004 and 2017, Black women were less likely to receive hEBRT (10.4% v 15.3%; 0.78 [0.75 to 0.81], P < .001). Black patients were consistently less likely to receive hypofractionated radiation for PC or BC, despite evidence suggesting that shorter regimens may lower rates of treatment noncompletion with similar oncologic outcomes.

Salvage external beam radiotherapy after HIFU failure in localized prostate cancer: A single institution experience

High-intensity focused ultrasound (HIFU) remains investigational as primary treatment for localized prostate cancer but is sometimes offered to select patients. At HIFU failure, data guiding salvage treatment is limited to small retrospective series with short follow-up. We evaluated our institutional experience using salvage radiation therapy (SRT) after HIFU failure. We conducted a retrospective analysis of patients with local failure post-HIFU who received salvage image-guided external beam radiation therapy (EBRT) delivered via intensity-modulated radiotherapy (IMRT). Our primary endpoint was biochemical failure-free survival (bFFS) defined as prostate-specific antigen (PSA) nadir + 2 ng/mL. Secondary endpoints included metastasis-free survival (MFS) and overall survival (OS). Endpoints were evaluated using Kaplan-Meier analysis. From 2013 to 2018, 12 out of 96 patients treated with primary HIFU received SRT via conventional or moderate hypofractionation. Median time from HIFU to SRT was 13.5 months. Seven patients had stage migration to high-risk disease at the time of SRT. Mean PSA prior to SRT was 8.2ug/L and mean nadir post-SRT was 1.2ug/L. Acute International Prostate Symptom Score (IPSS) as well as International Index of Erectile Dysfunction (IIEF) scores were similar to baseline (p = 0.5 and 0.1, respectively). Late toxicities were comparable to those reported after primary EBRT for localized prostate cancer. At a median follow-up of 46 months, the OS was 100%. The 5-year bFFS and MFS were both 83.3%. To our knowledge, we report one of the largest series on contemporary SRT post HIFU failure. We show that SRT is feasible, effective and carries no additional acute or delayed toxicity.

PHSOR04 Presentation Time: 12:45 PM: Investigating the Implications of a Newly-Available Higher Initial Source Strength for Ultrahypofractionated High-Dose-Rate 192Ir Brachytherapy in Prostate Monotherapy

<h3>Purpose</h3> Recently, ultrahypofractionated (UHF) regimens for high-dose-rate (HDR) Ir-192 prostate monotherapy have been becoming more popular. However, as fewer fractions are being used, the dose per fraction and, correspondingly, the delivery time per fraction increase. For example, the delivery time for a single-fraction regimen (∼19 Gy) is more than triple the delivery time per fraction in a 9-fraction regimen (∼6 Gy/fraction). As the source strength decreases exponentially over time, delivery times can be longer than 30 minutes for single-fraction regimens which is on the same magnitude as plausible values for prostate repair half-time. As radiobiological models show a supra-linear relationship between biological effective dose (BED) and delivery time, the aim of this investigation was to quantify the impact of adopting a newly-available 61050 U source strength to reduce delivery times in three common prescription regimens: two UHF regimens (1-fx and 2-fx) and a moderate hypofractionation (9-fx). <h3>Materials and Methods</h3> The simplified BED was estimated using the linear quadratic (LQ) model in its traditional form BED_T=nd(1+d/α/β). To account for the sublethal damage repair during protracted delivery, the Lea-Catcheside factor, g₀, was used to modify the two-track term of the LQ model, β, such that BED=nd(1+g₀d/α/β) with radiobiological parameters of α/β=3.0 Gy and repair half-time of 0.27 h drawn from AAPM TG-137 recommendations. Calculations were initially performed assuming 40700 U (10 Ci) of Ir-192 with a 90-day exchange cycle for 9 × 6 Gy, 2 × 13.5 Gy, and 1 × 19Gy regimens. This was repeated using a 61050 U (15 Ci) source Delivery time was linearly scaled based on 19 Gy prescription dose delivered in 15 minutes. <h3>Results</h3> Compared with the BED_T, the inclusion of g₀ decreased the BED_T by up to 30%. Of the three prescriptions studied, both BED_T and relative BED (BED/BED_T) were lowest for the 1-fx regimen. The relative BED is shown in Figure 1. For the 9-fx regimen, BED_T=162.0 Gy and the relative BED using 40700 U and 61050 U sources ranged from 0.906-0.957 and 0.935-0.971, respectively. For the 2-fx regimen, BED_T=148.5 Gy and the relative BED using 40700 U and 61050 U sources ranged from 0.815-0.909 and 0.867-0.937, respectively. For the 1-fx regimen, BED_T=139.3 Gy and the relative BED using 40700 U and 61050 U sources ranged from 0.692-0.841 and 0.773-0.889, respectively. As seen in Figure 1, the resultant change in relative BED is similar going from 1 to 2 fraction schemes as with going from 2 to 9 fraction schemes, mainly due to the exponential nature of g₀ against delivery time. The 61050 U source has an increased dose rate for nearly half (∼43 days) of a quarterly (90-day) source exchange cycle before decaying to 40700 U. <h3>Conclusions</h3> A BED calculation which incorporated sublethal damage repair was compared against the traditional BED_T. Relative BED was reduced by up to 30% in the 1-fx regimen for prostate monotherapy due to the fast intrafractional sublethal damage repair time in prostate paired with increasingly longer delivery times. The newly-available 61050 U source may provide one practical method for an institution to recoup BED for nearly half (∼43 days) of a typical 90-day source exchange cycle before decaying to 40700 U. Future work will study the impact on other common HDR brachytherapy sites such as cervix, vagina, breast, and skin.

Early Institutional Experience of Ultra-Hypofractionated Breast Radiotherapy in a Large Academic Cancer Center

<h3>Purpose/Objective(s)</h3> Ultra-hypofractionated radiotherapy (U-HFRT) is non-inferior to moderate hypofractionation (M-HFRT) for local control following breast-conserving surgery for early-stage breast cancer and is safe in terms of normal tissue toxicity. Our objective was to evaluate early institutional experience of U-HFRT in a real-world setting at a large academic cancer center. <h3>Materials/Methods</h3> Stage 0-II breast cancer patients who received adjuvant whole breast irradiation (WBI) or partial breast irradiation (PBI) between May 2020 and March 2021 were compiled. Patients were divided into 2 cohorts: U-HFRT (26 Gy in 5 daily fractions) and M-HFRT (40.05 Gy in 15 fractions). Clinical and treatment characteristics were extracted from medical records and displayed using descriptive statistics. Physician-assessed skin toxicity was collected for patients treated with U-HFRT during RT and at follow-up visits using the RTOG radiation morbidity scale. Associations between toxicity and clinical/treatment characteristics were determined using mixed effects logistic regression, accounting for time. Comparisons between the U-HFRT and M-HFRT cohorts were performed using the Wilcoxon rank sum test (continuous) and Chi-square/Fisher's exact test (categorical). <h3>Results</h3> Median age at diagnosis for the entire cohort was 60.5 years: U-HFRT 66.2 years and M-HFRT 55.1 years (p<0.001). For the U-HFRT cohort, 70% had hormone-receptor positive invasive breast cancer (70% pT1c, 95% pN0) and 20% had DCIS. WBI/PBI was delivered to 385 patients, of which 188 (49%) received U-HFRT. For these patients, the majority (72%) received WBI, 28% PBI and a boost was used in 26%, compared to 96%, 4% and 47%, respectively, for those treated with M-HFRT (p<0.001). Grade 1 RTOG skin toxicity significantly improved over time for patients who received U-HFRT: 37% during RT, 57% within 90 days post-RT and 6% >1-year post-RT (p<0.001). Grade 2 toxicity was minimal (5% within 90 days post-RT) and there were no grade 3 toxicities. Age, RT volume (WBI vs. PBI) and chemotherapy were not associated with toxicity for U-HFRT; however, increased toxicity was observed for patients who received a boost (p<0.001). Factors associated with increased usage of U-HFRT were older age, use of PBI, no boost and no breast reconstruction (p<0.001). <h3>Conclusion</h3> U-HFRT was rapidly adopted at our institution for early-stage breast cancer and is associated with low rates of reported skin toxicity. The use of U-HFRT was greatest in patients with low-risk breast cancer, consistent with a conservative approach to implementation in a real-world setting.

A Pilot Study of Moderately Hypo-Fractionated Whole Pelvic Radiotherapy with Concurrent Chemotherapy and Image-Guided High Dose Rate Brachytherapy for Locally Advanced Cervical Carcinoma

<h3>Purpose/Objective(s)</h3> The standard treatment of locally advanced cervical carcinoma (LACC) is whole pelvic radiotherapy (WPRT) with concurrent cisplatin and intracavitary brachytherapy (ICBT). EBRT is typically delivered to a dose of 45-50.4 Gray at 1.8-2 Gray per fraction. While moderate hypofractionation (H-EBRT) have been practiced, prospective evidence is limited. We evaluated the role of H-EBRT in terms of toxicities and clinical outcome in LACC. <h3>Materials/Methods</h3> 50 patients of squamous cell carcinoma of cervix were recruited in this prospective interventional trial between December 2018-December 2021 (CTRI/2018/11/016415). Patients were treated with WPRT 40 Gray in 16 fractions over 3.5 weeks with boost to pelvic lymph nodes 10 Gray in 4 fractions with 3-DCRT and concurrent cisplatin weekly 40 mg/m² followed by image guided high dose rate ICBT 7Gray in 4 fractions. Cumulative EQD2 (equivalent dose at 2 Gray per fraction) for high-risk clinical target volume and organs at risk were derived. Acute and late toxicities were recorded as per CTCAE version 4.0 and RTOG criteria respectively. Disease free survival (DFS) and overall survival (OS) were estimated by Kaplan Meier method <h3>Results</h3> Patient characteristics are summarized in Table 1. All patients completed intended course of treatment. 6 patients received nodal boost. Median number of concurrent chemotherapy cycles were 4 (range 3-5). Median (range) cumulative EQD2 for HR-CTV, rectum, bladder and sigmoid were 80.15 (68-104.9), 65.91 (51.1-75.18), 82.05 (58.58-94.96) and 55.96 (46.5-86.76) respectively. Acute ≥ Grade 2 and ≥ Grade 3 gastrointestinal (GI), genitourinary (GU), anemia, leucopenia, and thrombocytopenia were seen in 20 (40%) and 10 (20%), 5 (10%) and 3 (6%), 10 (20%) and 3 (6%), 15 (30%), and 4 (8%), 6 (12%), and 3 (6%), respectively. Late grade 2 and grade 3 GI toxicity was seen in 6 (12%) and 2 (4%) patients and late grade 2 GU toxicity were observed in 3 (6%) patients. Three patients had developed recurrence at the time of last follow-up and all three died from disease. Estimated 2- and 3-year overall survival was 94.9% and 90.6% respectively and 2- and 3-year DFS was 92.7% and 92.7% respectively. <h3>Conclusion</h3> Moderately hypo-fractionated WPRT is well tolerated with acceptable acute and late toxicity profiles and yielded excellent clinical outcome. This schedule would lead to lesser overall treatment time, increased compliance and also be resource sparing and cost effective. Longer follow up would yield more data on late toxicity. Randomized study comparing this schedule with conventional fractionated schedule is warranted.

Ultra-Hypo Fractionated Prostate IGRT with HDR Brachytherapy Boost as Compared to a Moderate-Hypo Fractionated Approach: Patient Reported Outcomes (PRO's) of a Phase Two Study Interim Analysis

<h3>Purpose/Objective(s)</h3> To report and compare PROs of an HDR brachytherapy (BB) combined to an ultra-hypo fractionated (UHF) prostate radiation therapy regimen as opposed to a moderate hypo fractionated (MHF). <h3>Materials/Methods</h3> This interim analysis of a prospective mono-centric phase 2 study includes 75 prostate cancer patients, mostly intermediate risk, recruited between July 2015 and September 2021. Using an image guided radiation therapy technique (IGRT), 25 Gy in 5 fractions plus 15 Gy HDR BB were delivered to the experimental arm (Exp). The control groups consisted of contemporary patients treated with IGRT and HDR BB (15 Gy) with 36 Gy in 12 fractions (Ctrl; n=119). IGRT treatment time is reported. Patient reported outcomes were collected using the International Prostate Symptom Score (IPSS) questionnaire at baseline and at each follow-up visits. A comparative linear mixed model analysis was performed on log transformed IPSS values. Expanded prostate cancer index composite-26 (EPIC-26) was also reported and compared between groups with a mixed model analysis. Biochemical relapse-free survival (BRFS) is reported. <h3>Results</h3> The 2 groups were similar with no statistical differences regarding: the median age (68 years), stage (T1C), Gleason scores (7), PSA (<10) and risk grouping (favorable intermediate). Median follow-up was 8 and 49 months respectively for Exp & Ctrl. The mixed model analysis showed that mean IPSS scores diverge with a significant difference in favor of Exp at 6, 12 and 24 months. Analysis of EPIC-26 data showed no differences throughout follow-up between Exp and Ctrl in all domains. To the patient's convenience, UHF median treatment was delivered in 7 days as compared to 17 days for MHF. Considering a short follow-up in the Exp group, its BRFS was 100% compared to 94.6 for Ctrl and these differences are not significative. <h3>Conclusion</h3> At the interim analysis, IPSS PROs for UHF treatment scheme with HDR BB seems to be significantly better tolerated at multiple FU time point compared to the control. However, there was no significant differences between groups reported with the EPIC-26. UHF treatment shorten treatment span by 10 days and given the short FU, seemingly provides similar BRFS. Therefore, we will pursue accrual to our phase 2 study.

Patient Reported Quality of Life after Moderately Hypofractionated Proton Beam Therapy or Intensity Modulated Radiation Therapy for Prostate Cancer

<h3>Purpose/Objective(s)</h3> We aim to quantify and compare changes in patient reported quality of life (PRQOL) after moderately hypofractionated (MHF) Proton Beam Therapy (PBT) or Intensity Modulated Radiation Therapy (IMRT) for prostate cancer (PC). <h3>Materials/Methods</h3> This multi-institutional analysis included patients with NCCN low or intermediate risk PC treated at 4 tertiary cancer centers with MHF PBT or IMRT with prospective PRQOL collection. Patients completed International Prostate Symptom Score (IPSS) and Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC) pre-treatment and at 3-to-6-month intervals starting at the end of treatment. EPIC is a questionnaire measuring health related quality of life (HRQOL) domains of genitourinary (GU), gastrointestinal (GI), sexual, and hormonal function. Questions are scored from 0 (no problem) to 4 (big problem). EPIC score of 3 or more was considered a meaningful QOL decrement. IPSS measures GU HRQOL; each question is measured from a score of 0 to 5 with a maximum score of 35. Baseline characteristics were compared with Chi squared and t test for IPSS. Models were limited to long term data, at 12 and 36 months. Generalized linear regression models testing effects of time, treatment, and their interaction were fit via Generalized Estimating Equations, controlling for age, race, and NCCN risk group. <h3>Results</h3> 287 IMRT and 485 PBT patients were included. Intermediate NCCN risk group (81.2 vs. 68.2%; p < 0.001), median age at diagnosis (70 vs 66.9 years; p < 0.001) were higher in the IMRT group. Mean IPSS was slightly worse at baseline in the PBT arm (+0.22; CI, -1.54 – 1.10; p=0.74) and slightly better at 3 years (-0.09; CI, -1.48 – 1.65; p=0.91). On Poisson regression controlling for age, race, and NCCN risk group, PBT IPSS trended worse at 12 months (OR, 1.19; CI, 0.98 - 1.44; p=0.077) without any difference at 36 months (OR, 1.08; CI, 0.80 - 1.26; p=0.94). Similarly, EPIC questionnaire for overall GI function trended worse with PBT at 12 months (CI, 0.83 - 16.27; p=0.085) without difference at 36 months (CI, 0.49 - 12.27, p=0.27). 4.9% and 4.8% patients in the PBT and IMRT arms, respectively, rated their overall GI function at 12 months as a severe problem. Among PBT and IMRT patients combined, severe GU concerns were unlikely at 12 months (GU frequency: 17.5; GU pain: 3.6; stream problem: 11.2%). <h3>Conclusion</h3> PRQOL showed a non-significant trend toward worse 1-year overall GI function and IPSS for PBT; this effect was not present at 3 years. In this multi-institutional, prospective study of PC, long-term GU and GI function was not significantly different between PBT or IMRT arms.

Intensity-modulated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): 2-year toxicity results from an open-label, randomised, phase 3, non-inferiority trial.

Localised prostate cancer is commonly treated with external beam radiotherapy and moderate hypofractionation is non-inferior to longer schedules. Stereotactic body radiotherapy (SBRT) allows shorter treatment courses without impacting acute toxicity. We report 2-year toxicity findings from PACE-B, a randomised trial of conventionally fractionated or moderately hypofractionated radiotherapy versus SBRT. PACE is an open-label, multicohort, randomised, controlled, phase 3 trial conducted at 35 hospitals in the UK, Ireland, and Canada. In PACE-B, men aged 18 years and older with a WHO performance status 0-2 and low-risk or intermediate-risk histologically-confirmed prostate adenocarcinoma (Gleason 4 + 3 excluded) were randomly allocated (1:1) by computerised central randomisation with permuted blocks (size four and six), stratified by centre and risk group to control radiotherapy (CRT; 78 Gy in 39 fractions over 7·8 weeks or, following protocol amendment on March 24, 2016, 62 Gy in 20 fractions over 4 weeks) or SBRT (36·25 Gy in five fractions over 1-2 weeks). Androgen deprivation was not permitted. Co-primary outcomes for this toxicity analysis were Radiation Therapy Oncology Group (RTOG) grade 2 or worse gastrointestinal and genitourinary toxicity at 24 months after radiotherapy. Analysis was by treatment received and included all patients with at least one fraction of study treatment assessed for late toxicity. Recruitment is complete. Follow-up for oncological outcomes continues. The trial is registered with ClinicalTrials.gov, NCT01584258. We enrolled and randomly assigned 874 men between Aug 7, 2012, and Jan 4, 2018 (441 to CRT and 433 to SBRT). In this analysis, 430 patients were analysed in the CRT group and 414 in the SBRT group; a total of 844 (97%) of 874 randomly assigned patients. At 24 months, RTOG grade 2 or worse genitourinary toxicity was seen in eight (2%) of 381 participants assigned to CRT and 13 (3%) of 384 participants assigned to SBRT (absolute difference 1·3% [95% CI -1·3 to 4·0]; p=0·39); RTOG grade 2 or worse gastrointestinal toxicity was seen in 11 (3%) of 382 participants in the CRT group versus six (2%) of 384 participants in the SBRT group (absolute difference -1·3% [95% CI -3·9 to 1·1]; p=0·32). No serious adverse events (defined as RTOG grade 4 or worse) or treatment-related deaths were reported within the analysis timeframe. In the PACE-B trial, 2-year RTOG toxicity rates were similar for five fraction SBRT and conventional schedules of radiotherapy. Prostate SBRT was found to be safe and associated with low rates of side-effects. Biochemical outcomes are awaited. Accuray.

51: Patient’s Reported Outcomes (PROS) of an Ultra-Hypo Fractionated (UHF) Prostate Image Guided Radiation Therapy (IGRT) with Hdr Brachytherapy Boost (BB) as Compared to a Moderate Hypo Fractionated (MHF) Approach: Interim Analysis of a Phase Two Study

51: Patient’s Reported Outcomes (PROS) of an Ultra-Hypo Fractionated (UHF) Prostate Image Guided Radiation Therapy (IGRT) with Hdr Brachytherapy Boost (BB) as Compared to a Moderate Hypo Fractionated (MHF) Approach: Interim Analysis of a Phase Two Study

Cost-effectiveness of Post-Mastectomy Radiotherapy (PMRT) for breast cancer in India: An economic modelling study.

The role of post-mastectomy radiotherapy (PMRT) for breast cancer is controversial when 3-or-less lymph nodes are metastatic. Apart from local control, survival and toxicity, cost also plays an important role in decision-making. A Markov model was designed to assess cost, health outcomes and cost-effectiveness of different radiotherapy techniques for management of PMRT patients. Thirty-nine scenarios were modelled based on type of radiotherapy, laterality, pathologic nodal burden, and dose fractionation. We considered a societal perspective, lifetime horizon and a 3% discount rate. The data on quality of life (QoL) was derived using the cancer database on cost and QoL. Published data on cost of services delivered in India were used. Post-mastectomy radiotherapy results in incremental quality adjusted life years (QALYs) that ranged from -0.1 to 0.38 across different scenarios. The change in cost ranged from estimated median savings of USD 62 (95% confidence intervals: -168 to -47) to incurring an incremental cost of USD 728 (650-811) across different levels of nodal burden, breast laterality and dose fractionation. For women with node-negative disease, disease-specific systemic therapy remains to be the preferred strategy. For women with node-positive disease, two-dimensional radiotherapy (2DRT) with hypofractionation is the most cost-effective strategy. However, a CT based planning is preferred when maximum heart distance (MHD) >1cm, irregular chest wall contour and inter-field separation >18cm. PMRT is cost-effective for all node-positive patients. With similar toxicity and effectiveness profile compared with conventional fractionation, moderate hypofractionation significantly reduces the cost of treatment and should be the standard of care. Conventional techniques for PMRT are cost-effective over newer modalities which provide minimal additional benefit, at high cost. The funding to collect primary data for study was provided by Department of Health Research, Ministry of Health and Family Welfare, New Delhi, wide letter number F. No. T.11011/02/2017-HR/3100291.

Moderately hypofractionated radiation therapy for breast cancer: A Brazilian cohort study

Results from numerous clinical trials have led to a consensus that moderately hypofractionated radiation therapy is the ideal postoperative irradiation treatment plan in patients with breast cancer (BC). However, there are specific situations such as chest wall (with or without breast reconstruction) and regional node irradiation that still face obstacles in its widespread use. There is a lack of evidence supporting the use of moderately hypofractionated irradiation from the Latin American context. This study aims to describe the profile and clinical outcomes of patients treated with moderate hypofractionation for both early-stage (Stage I and II) and locally advanced BC (Stage III) regardless of the type of surgery in a Brazilian Oncology Center. All patients with non-metastatic BC who were treated with moderately hypofractionated schedules of 40Gy in 15 fractions or 42.4Gy in 16 fractions between 2010 to 2019 at Hospital Sírio-Libanês, Brazil were retrospectively analyzed. The rates of local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distance recurrence-free survival (DRFS) and overall survival (OS) were estimated. Acute and late toxicity profiles were accessed for the entire cohort. A total of 670 patients were included. The median age was 57 years and the median follow-up time was 31 months. Most of the patients had stage I and II breast cancer, and 81.6% underwent breast-conserving surgery. Of the 123 women who underwent mastectomy treatment, 29% (n=37) had immediate reconstruction with implants and 28% (n=35) with autologous tissue. Seventy-one per cent of the patients presented luminal subtype tumour and 84.3% received adjuvant hormonal therapy. Chemotherapy was administered to almost half of the patients and all 80 patients with Her-2 positive disease received trastuzumab-based systemic therapy. One-third of patients received regional node irradiation; boost was performed in 41.1% of treatments. The 5-year LRFS, RRFS, DRFS and OS was 95.6%, 97.6%,92.2% and 95.9%, respectively. Acute and late side effects profile were mild and only 2.9% of patients developed grade 3 dermatitis. Among patients with breast implants, 11.4% had capsular contracture. In this Brazilian institution experience, moderately hypofractionated irradiation to the breast, chest wall (with or without breast reconstruction), and regional lymph nodes was safe and with an acceptable toxicity profile. None.

Lessons learned after one year of COVID-19 from a urologist and radiotherapist view: A German survey on prostate cancer diagnosis and treatment.

IntroductionSince the beginning of the pandemic in 2020, COVID-19 has changed the medical landscape. International recommendations for localized prostate cancer (PCa) include deferred treatment and adjusted therapeutic routines.Materials and methodsTo longitudinally evaluate changes in PCa treatment strategies in urological and radiotherapy departments in Germany, a link to a survey was sent to 134 institutions covering two representative baseline weeks prior to the pandemic and 13 weeks from March 2020 to February 2021. The questionnaire captured the numbers of radical prostatectomies, prostate biopsies and case numbers for conventional and hypofractionation radiotherapy. The results were evaluated using descriptive analyses.ResultsA total of 35% of the questionnaires were completed. PCa therapy increased by 6% in 2020 compared to 2019. At baseline, a total of 69 radiotherapy series and 164 radical prostatectomies (RPs) were documented. The decrease to 60% during the first wave of COVID-19 particularly affected low-risk PCa. The recovery throughout the summer months was followed by a renewed reduction to 58% at the end of 2020. After a gradual decline to 61% until July 2020, the number of prostate biopsies remained stable (89% to 98%) during the second wave. The use of RP fluctuated after an initial decrease without apparent prioritization of risk groups. Conventional fractionation was used in 66% of patients, followed by moderate hypofractionation (30%) and ultrahypofractionation (4%). One limitation was a potential selection bias of the selected weeks and the low response rate.ConclusionWhile the diagnosis and therapy of PCa were affected in both waves of the pandemic, the interim increase between the peaks led to a higher total number of patients in 2020 than in 2019. Recommendations regarding prioritization and fractionation routines were implemented heterogeneously, leaving unexplored potential for future pandemic challenges.

Ultra-Hypofractionated vs. Moderate Fractionated Whole Breast Three Dimensional Conformal Radiotherapy during the COVID-19 Pandemic.

Background and Objectives: Reducing time of treatment during COVID-19 outbreaks has been recommended by the leading Radiation Oncology societies. Still minimizing radiation induced tissue toxicity is one of the most important issues in breast cancer patients. The study aimed to investigate compliance, clinical and dosimetry normal tissue toxicity, and cosmetic results between moderated and ultra-fractionated regimes for breast cancer patients during COVID-19 pandemic. Materials and Methods: This pilot prospective randomized study included 60 patients with early breast cancer after preserving surgery, 27 patients advocated to ultra-hypofractionated whole-breast three dimensional (3D) conformal radiotherapy of 26 Gy in 5 fractions over 1 week and 33 patients with moderate fractionated breast 3D conformal radiotherapy patients between March 2020 and July 2020, during the COVID pandemic outbreak. The compliance to treatment, dosimetric parameters, acute and late skin toxicity, subcutaneous tissue toxicity, cosmetic results and clinical follow up for 18 months for the two regimes were analyzed and compared. Results: When two regimes were compared 5 fraction group had significantly lower prevalence of newly infected cases of SARS-CoV-2 and thus delayed/interrupted treatment (p = 0.05), comparable grade 1 CTCAE v5, acute skin toxicity (p = 0.18), Grade 1 Radiation Morbidity Scoring Scheme (RESS) subcutaneous tissue toxicity (p = 0.18), Grade 1 RESS late skin toxicity (p = 0.88) and cosmetic results (p = 0.46). Dosimetric results reveled that patients in 5 fraction group received significantly lower median ipsilateral lung doses (p < 0.01) in addition to left breast cancer patients that received significantly lower median heart dose (p < 0.01) and median left anterior descending artery (LAD) dose (p < 0.01). Conclusion: Ultra-hypofractionated radiotherapy for breast cancer is comparable to moderate hypofractionation regimen regarding grade 1 acute skin toxicity, grade 1 subcutaneous tissue toxicity, late skin toxicity and cosmetic results. Application of ultra-hypofractionated radiotherapy with significantly lower radiation doses for lung and heart could be crucial in reducing the risk of acute/late pulmonary and heart radiation-induced toxicity.

PO-1382 Moderate hypofractionation for prostate cancer with fiducials markers

PO-1382 Moderate hypofractionation for prostate cancer with fiducials markers

GOECP/SEOR radiotheraphy guidelines for non-small-cell lung cancer.

Non-small cell lung cancer (NSCLC) is a heterogeneous disease accounting for approximately 85% of all lung cancers. Only 17% of patients are diagnosed at an early stage. Treatment is multidisciplinary and radiotherapy plays a key role in all stages of the disease. More than 50% of patients with NSCLC are treated with radiotherapy (curative-intent or palliative). Technological advances-including highly conformal radiotherapy techniques, new immobilization and respiratory control systems, and precision image verification systems-allow clinicians to individualize treatment to maximize tumor control while minimizing treatment-related toxicity. Novel therapeutic regimens such as moderate hypofractionation and advanced techniques such as stereotactic body radiotherapy (SBRT) have reduced the number of radiotherapy sessions. The integration of SBRT into routine clinical practice has radically altered treatment of early-stage disease. SBRT also plays an increasingly important role in oligometastatic disease. The aim of the present guidelines is to review the role of radiotherapy in the treatment of localized, locally-advanced, and metastatic NSCLC. We review the main radiotherapy techniques and clarify the role of radiotherapy in routine clinical practice. These guidelines are based on the best available evidence. The level and grade of evidence supporting each recommendation is provided.