Moderate Hypofractionated Radiotherapy Research Articles

Functional imaging guided stereotactic ablative body radiotherapy (SABR) with focal dose escalation and bladder trigone sparing for intermediate and high-risk prostate cancer: study protocol for phase II safo trial

BackgroundStereotactic ablative body radiotherapy (SABR) is an emerging treatment alternative for patients with localized low and intermediate risk prostate cancer patients. As already explored by some authors in the context of conventional moderate hypofractionated radiotherapy, focal boost of the index lesion defined by magnetic resonance imaging (MRI) is associated with an improved biochemical outcome. The objective of this phase II trial is to determine the effectiveness (in terms of biochemical, morphological and functional control), the safety and impact on quality of life, of prostate SABR with MRI guided focal dose intensification in males with intermediate and high-risk localized prostate cancer.MethodsPatients with intermediate and high-risk prostate cancer according to NCCN definition will be treated with SABR 36.25 Gy in 5 fractions to the whole prostate gland with MRI guided simultaneous integrated focal boost (SIB) to the index lesion (IL) up to 50 Gy in 5 fractions, using a protocol of bladder trigone and urethra sparing. Intra-fractional motion will be monitored with daily cone beam computed tomography (CBCT) and intra-fractional tracking with intraprostatic gold fiducials. Androgen deprivation therapy (ADT) will be allowed. The primary endpoint will be efficacy in terms of biochemical and local control assessed by Phoenix criteria and post-treatment MRI respectively. The secondary endpoints will encompass acute and late toxicity, quality of life (QoL) and progression-free survival. Finally, the subgroup of high-risk patients will be involved in a prospective study focused on immuno-phenotyping.DiscussionTo the best of our knowledge, this is the first trial to evaluate the impact of post-treatment MRI on local control among patients with intermediate and high-risk prostate cancer undergoing SABR and MRI guided focal intensification. The results of this trial will enhance our understanding of treatment focal intensification through the employment of the SABR technique within this specific patient subgroup, particularly among those with high-risk disease, and will help to clarify the significance of MRI in monitoring local responses. Hopefully will also help to design more personalized biomarker-based phase III trials in this specific context. Additionally, this trial is expected to be incorporated into a prospective radiomics study focused on localized prostate cancer treated with radiotherapy.Trial registrationClinicaltrials.gov identifier: NCT05919524; Registered 17 July 2023.Trial SponsorIRAD/SEOR (Instituto de Investigación de Oncología Radioterápica / Sociedad Española de Oncología Radioterápica).Study settingClinicaltrials.gov identifier: NCT05919524; Registered 17 July 2023.Trial statusProtocol version number and date: v. 5/ 17 May-2023. Date of recruitment start: August 8, 2023. Date of recruitment completion: July 1, 2024.

Efficiency of moderately hypofractionated radiotherapy in NSCLC cell model.

The current standard of radiotherapy for inoperable locally advanced NSCLCs with single fraction doses of 2.0 Gy, results in poor outcomes. Several fractionation schedules have been explored that developed over the past decades to increasingly more hypofractionated treatments. Moderate hypofractionated radiotherapy, as an alternative treatment, has gained clinical importance due to shorter duration and higher patient convenience. However, clinical trials show controversial results, adding to the need for pre-clinical radiobiological studies of this schedule. We examined in comparative analysis the efficiency of moderate hypofractionation and normofractionation in four different NSCLC cell lines and fibroblasts using several molecular-biological approaches. Cells were daily irradiated with 24x2.75 Gy (moderate hypofractionation) or with 30x2 Gy (normofractionation), imitating the clinical situation. Proliferation and growth rate via direct counting of cell numbers, MTT assay and measurements of DNA-synthesizing cells (EdU assay), DNA repair efficiency via immunocytochemical staining of residual γH2AX/53BP1 foci and cell surviving via clonogenic assay (CSA) were experimentally evaluated. Overall, the four tumor cell lines and fibroblasts showed different sensitivity to both radiation regimes, indicating cell specificity of the effect. The absolute cell numbers and the CSA revealed significant differences between schedules (P < 0.0001 for all employed cell lines and both assays) with a stronger effect of moderate hypofractionation. Our results provide evidence for the similar effectiveness and toxicity of both regimes, with some favorable evidence towards a moderate hypofractionation. This indicates that increasing the dose per fraction may improve patient survival and therapy outcomes.

Evaluating the Response of Hypofractionated Radiotherapy verses Conventional Radiotherapy with Concurrent Cisplatin in Advanced Fixed Node Head and Neck Carcinoma

Background: The evolution of radiotherapy over recent decades has reintroduced the hypofractionation for many tumour sites with similar outcomes to those of conventional fractionated radiotherapy. The use of hypofractionation in locally advanced head and neck cancer (LAHNC) has been already used, however, its use has been restricted to only a few countries. The aim of this trial was to evaluate the safety and feasibility of moderate hypofractionated radiotherapy (HYP-RT) with concomitant cisplatin (CDDP). Objectives: To evaluate the efficacy of hypofractionated radiotherapy in advanced unresectable head neck cancer, in terms of response rate and evaluate the local and systemic toxicities of hypofractionated regimen with symptomatic improvement of radiotherapy and treatment compliance. Methods: A total of 50 cases of locally advanced head and neck cancer (stage cT4b and/or N3) without any evidence of distant metastasis were included in this study. These 50 cases were randomly distributed into study and control group containing 25 each. Radiotherapy consists of a single fraction of 6 Gy Per week for a total of 6 weeks. If the patient received less than 6weeks of treatment, he/she was excluded from study. Total dose given was 36 Gy in 6 fractions. All the patients were treated by unilateral or bilateral portal till 24 Gy and then off cord planning was done. Patients with complete disease regression after initially planned 36 Gy (BED-57.6Gy, considering alpha/beta of 10 and corresponding EQD2-48Gy) were offered further dose escalation depending upon tumour regression status, tolerability and toxicity according to institutional guidelines. Partial responders are given no treatment up to end of treatment period. Results: Among the study and control group, incidence of carcinoma of tonsil was 12% and 20%, carcinoma of base of tongue was 24% and 16%, carcinoma larynx 16% and 24%, respectively and Hematological toxicities (reference to blood hemoglobin level), Renal (reference to blood urea) were assessed according to WHO toxicity criteria in all cases weekly up to six weeks Among the study and control group, 8% and 12% had no acute hematologic reactions (χ2 = 0.22, p &gt; 0.05), 56% and 48% had grade I hematologic reactions (χ2 = 0.32 p &gt; 0.05,), 28% and 36% had grade II hematologic reactions (χ2 = 0.36, p &gt; 0.05) and 8% and 4% had grade III hematologic reactions (χ2 = 0.35, p &gt; 0.05) respectively. No patient had had grade IV hematological toxicity. Among the study and control group, 80% and76% had no acute renal toxicity. (χ2 = 0.11, p &gt; 0.05), 20% and 24% had grade I hematologic reactions (χ2= 0.11 p &gt; 0.05). No patients from either group develop grade II, III and IV renal toxicity. Conclusions: HYP-RT with concomitant CDDP was considered feasible for LAHNC, and the rate of acute toxicity was comparable to that of standard concomitant chemoradiation. A feeding tube was necessary for most patients during treatment. Further investigation of this strategy is warranted.

A Japanese multi-institutional phase II study of moderate hypofractionated intensity-modulated radiotherapy with image-guided technique for prostate cancer.

The aim of this multi-institutional phase II study was to confirm the safety and the potential efficacy of moderately hypofractionated intensity-modulated radiotherapy (IMRT) with prostate-based image-guidance for Japanese patients. Patients with low- or intermediate-risk localized prostate cancer were eligible. Patients with a part of high risk (having only one of the following factors, cT3a, 20 < PSA ≤ 30, or GS = 8 or 9) were also included. Hypofractionated IMRT using daily image-guided technique with prostate matching was performed with a total dose of 70Gy in 28 fractions. Neoadjuvant hormonal therapy for 4-8months was mandatory for patients with intermediate or high-risk prostate cancer. From 20 institutions, 134 patients enrolled. The median follow-up was 5.16years (range, 1.43-6.47years). The number of patients with low, intermediate, and high-risk prostate cancer was 20, 80, and 34, respectively. The 5-year overall, biochemical failure-free, and clinical failure-free survival was 94.5%, 96.0%, and 99.2%, respectively. The 5-year biochemical failure-free survival for patients with low-, intermediate-, and high-risk disease was 94.1%, 97.4%, and 93.9%, respectively. The incidences of grade 2 gastrointestinal (GI) and genitourinary (GU) late toxicities at 5years were 5.3% and 5.3%, respectively. There are no acute or late toxicities ≥ grade 3. Of 124 patients who were followed for up to 5years, the grade 2 late GU or GI toxicities were 10.5% (90% confidence intervals, 6.3-16.2%, p = 0.0958). The safety and efficacy of moderately hypofractionated IMRT with prostate-based image-guidance was confirmed among Japanese patients with prostate cancer.

Radiotherapy Combined with a Radiosensitizer for Bacillus Calmette-Guérin–unresponsive Non–muscle-invasive Carcinoma In Situ Bladder Cancer: An Open-label, Single-arm, Multicenter, Phase 2 European Organisation for Research and Treatment of Cancer Trial

Radical cystectomy with pelvic lymph node dissection and urinary diversion is the standard of care for patients with bacillus Calmette-Guérin (BCG)-unresponsive non–muscle-invasive bladder cancer (NMIBC). However, many patients are unwilling or unable to undergo such major surgery associated with high morbidity and a negative impact on quality of life. Chemoradiotherapy is an established treatment option for muscle-invasive bladder cancer. However, it has not been investigated adequately in NMIBC until now. The European Organisation for Research and Treatment of Cancer (EORTC) 2235 study (NCT06310369) is designed as a multicenter, prospective, international, phase 2 trial of moderate hypofractionated radiotherapy combined with a radiosensitizer in BCG-unresponsive NMIBC patients with carcinoma in situ (CIS) who are not eligible for or declined to undergo radical cystectomy. Patients who have received nadofaragene firadenovec or TAR-200 are eligible. The primary endpoint is the 6-mo complete response (CR) rate defined by the absence of CIS proven by a control biopsy of the bladder. The secondary endpoints include overall survival, progression-free survival, durability of CR, grade 3–4 adverse events rate, patients’ quality of life, and organ preservation rate. Patient summaryIntravesical instillation of bacillus Calmette-Guérin is the standard treatment of non–muscle-invasive, also coined as superficial, bladder cancer. In case the cancer recurs, even superficially, there is no other proven treatment than a radical cystectomy—the surgical removal of the bladder. Although the surgical technique has improved dramatically over the past few years, it remains contraindicated in patients with severe comorbidities. In addition, because it affects the quality of life, patients may reject this option. This study will assess the efficacy of external beam radiotherapy, a robust alternative to surgery in muscle-invasive bladder cancer. Radiotherapy will be administered 5 d a week for 4 wk. It will be associated with a “radiosensitizer,” an intravenous or oral drug, during the radiotherapy treatment. The study will measure the proportion of patients remaining recurrence free at 6 mo and thereafter. It will also evaluate the safety of the treatment and its impact on quality of life.

Comprehensive 3DCRT Hypofractionated Radiotherapy Schedule for Localized Prostate Adenocarcinoma in the Era of IMRT: Dosimetric and Endoscopic Analysis.

Background: Moderate hypofractionated radiotherapy (MHRT) has emerged as the preferred treatment modality for localized prostate cancer based on randomized controlled studies regarding efficacy and toxicity using contemporary radiotherapy techniques. In the setting of MHRT, available data on dosimetric parameters and late rectal toxicity are limited. Aim: To present the effects of MHRT on late rectal toxicity while conducting an extensive dosimetric analysis in conjunction with rectoscopy results. Methods: This is a prospective study including patients with intermediate-risk prostate adenocarcinoma. All patients were treated with MHRT 44 Gy in 16 fractions to the seminal vesicles and to the prostate, followed by a sequential boost to the prostate alone of 16.5 Gy in 6 fractions delivered with three-dimensional conformal radiation therapy (3DCRT). Acute and late toxicity were assessed. Endoscopy was performed at baseline, every 3 months post-therapy for the first year, and every 6 months for the year after. The Vienna Rectoscopy Score (VRS) was used to assess rectal mucosal injury related to radiotherapy. Dosimetric analysis for the rectum, rectal wall, and its subsegments (upper, mid, and low 1/3) was performed. Results: Between September 2015 and December 2019, 20 patients enrolled. Grade 1 late gastrointestinal toxicity occurred in 10% of the patients, whereas 5% had a grade ≥2. Twelve months post radiotherapy: 4 (20%) patients had VRS 1; 2 (10%) patients had VRS 2; 1(5%) patient had VRS 3. 24 months post radiotherapy, VRS 1 was observed in 4 patients (20%) and VRS 2 in 3 (15%) patients. The dosimetric analysis demonstrated noticeable variations between the rectum, rectal wall, and rectal wall subsegments. The dosimetric analysis of the rectum, rectal wall, and its mid and low segments with respect to rectoscopy findings showed that the higher dose endpoints V52.17Gy and V56.52Gy are associated with rectal mucosal injury. Conclusions: A thorough delineation of the rectal wall and its subsegments, together with the dosimetric analysis of these structures, may reduce late rectal toxicity. Dosimetric parameters such as V52.17Gy and V56.52Gy were identified to have a significant impact on rectal mucosal injury; additional dose endpoint validation and its relation to late GI toxicity is needed.

P054 - Toxicity results of a multicentre randomized phase 3, non-inferiority trial on moderate hypofractionated radiotherapy.

P054 - Toxicity results of a multicentre randomized phase 3, non-inferiority trial on moderate hypofractionated radiotherapy.

A novel, multi-active emollient for the prevention of acute radiation dermatitis in breast cancer patients: a randomized clinical trial.

To investigate the efficacy of a novel, multi-active emollient in preventing and managing acute radiation dermatitis (ARD) in breast cancer patients undergoing moderate hypofractionated (HF) radiotherapy (RT) compared to standard of care. A monocentric, open-label, randomized clinical trial (RCT) with breast cancer patients receiving moderate HF (dose: 40.05-55.86Gy, fractions: 15-21) was conducted between January 2022 and May 2023. The experimental group received the novel emollient, while the control group received the standard skin care. Patients applied the skin care products twice daily during the complete RT course. The primary outcome was the severity of ARD at the final RT session measured by the modified Radiation Therapy Oncology Group (RTOG) criteria. Secondary outcomes included patient symptoms, quality of life (QoL), and treatment satisfaction. A total of 100 patients with 50 patients per group were enrolled. In the control group, 50% of the patients developed RTOG grade 1 ARD and 48% grade 2 or higher, while in the experimental group, the severity of ARD was significantly lower with 82% grade 1 and 16% grade 2 ARD (P = .013, χ2-test). The frequency and severity of xerosis were significantly lower in the experimental compared to the control group (Ps ≤ .036, Mann Whiney U test). The impact of ARD on the QoL was low, and treatment satisfaction was high in both groups, with no significant difference. This RCT shows that the novel, multi-active emollient significantly reduced the ARD RTOG grade. Research in a more diverse patient population is warranted. ClinicalTrials.gov: NCT04929808 (11/06/2021).

Physician and Patient-Reported Outcomes of a Phase III Trial of Ultra-Hypofractionated vs. Moderate Hypofractionated Radiotherapy to the Whole Breast after Breast-Conserving Surgery

To report a final analysis evaluating physician and patient-reported outcomes of early breast cancer patients receiving moderate hypofractionation or ultra-hypofractionated whole breast radiotherapy (RT). Between April 4, 2018, and February 11, 2020, patients with localized breast cancer (T1-T3, N0-N1, and M0) managed with breast-conserving surgery (BCS) were enrolled. Patients were randomized to receive whole breast RT with moderate hypofractionation to 40 Gy in 15 fractions (Arm A) or ultra-hypofractionation to 25 Gy in 5 fractions (Arm B). An optional concurrent integrated boost to 48 Gy on Arm A or 30 Gy on Arm B was allowed. Early toxicity (<3 months), late toxicity (> 3 months), quality of life (QOL), cosmesis, Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), and deterioration of cosmesis were analyzed. One hundred and seven patients were randomized to moderate hypofractionation (n = 54) or ultra-hypofractionation (n = 53). With a median follow-up of 36 months, no significant differences in patient characteristics were noted between the two arms. There were no patients with a grade ≥3 or higher toxicity. Grade 2 toxicities were 7.4% in Arm A and 7.5% in Arm B, and primarily consisted of radiation dermatitis (6 patients), fibrosis (1 patient) and lymphedema (1 patient). The average Harvard Cosmesis score and overall QoL were similar between arms at all time points, with no patients developing cosmetic deterioration. Patient-reported moderate to severe radiation skin burns were more commonly reported in Arm A (21.05%) vs. Arm B (6.25%) at the end of treatment (EOT) (p = 0.078). At EOT, patients receiving moderate hypofractionation had higher mean toxicity scores in breast tenderness (2.66 vs. 1.5, p = 0.018), skin flaking or peeling (0.63 vs. 0.06, p = 0.035), blistering (0.74 vs. 0.06, p = 0.028), pruritis (2.53 vs. 0.87, p < 0.001), erythema (4.24 vs. 2.0, p <0.001), telangiectasias (1.0 vs. 0.28, p = 0.021). Additionally, patients receiving moderate hypofractionation reported significantly worse changes from baseline at EOT in breast tenderness (-2.25 vs. -.86, p = 0.02), telangiectasia (-0.81 vs. 0.18, p = 0.012), skin discoloration (-4.31 vs. -1.04, p < 0.001), skin flaking or peeling (-.55 vs. 0.04, p = 0.053), blistering (-0.82 vs. -0.07, p = 0.033), and pruritus (-2.27 vs. -.67, p = 0.002). There was a return to baseline in all patient-reported breast domains by 3 months (p >0.05) in both arms. Ultra-hypofractionated whole breast irradiation, consisting of 25 Gy in 5 fractions, provided comparable provider assessed toxicity and cosmetic outcomes to 40 Gy in 15 fractions. At the EOT assessment, ultra-hypofractionation had a better patient reported toxicity profile. Our findings provide further evidence to support daily ultra-hypofractionated whole breast radiotherapy as an appropriate treatment option for early-stage breast cancer.

Moderate hypofractionated adjuvant radiotherapy with simultaneous integrated boost for breast cancer

Moderate hypofractionated adjuvant radiotherapy with simultaneous integrated boost for breast cancer

Beyond the heart in hypofractionated radiotherapy and in the transition from 3D to IMRT/VMAT.

The knowledge of the risks induced by radiation with hypofractionation regimens has only recently been estimated together with its implementation as a management standard. However, the dose to other risk organs with intensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) is not clear, that is why this is only a reference study of radiation doses to organs at risk in hypofractionation in our center. We completed a retrospective and observational analysis of 1398 patients treated with adjuvant hypofractionated radiotherapy from 2015 to 2018, using the clinical records and dose-volume histogram of patients treated with moderate hypofractionated adjuvant radiotherapy. To analyze the institutional experience on the dosimetry of the esophagus and liver as risk organs in the use of moderate adjuvant hypofractionated radiotherapy in breast cancer. The dosimetry of the esophagus was 3271 cGy DMax, 177 cGy DMed, 68 cGy D50%, 500 cGy DcMAX with 3D RT and 4124 cGy DMax, 1242 cGy DMed, 934.50 cGy D50%, 3213 cGy DcMAX with IMRT/VMAT and the dosimetry for the liver was for right breast cancer 466 cGy DMed, 102 cGy D50% and 8% V20, for left breast cancer 22 cGy DMed, 6.10 cGy D50% and 0.3% V20. The statistically significant differences in irradiation show the lack of consensus on the optimal restrictions in hypofractionation regimens to reduce clinical sequela; consequently, the variability in the specification of each radiation oncologist is observed; standardization in our center can lead to improvement in the quality of treatments.

Hypofractionated Radiotherapy in Localized, Low-Intermediate-Risk Prostate Cancer: Current and Future Prospectives.

At the time of diagnosis, the vast majority of prostate carcinoma patients have a clinically localized form of the disease, with most of them presenting with low- or intermediate-risk prostate cancer. In this setting, various curative-intent alternatives are available, including surgery, external beam radiotherapy and brachytherapy. Randomized clinical trials have demonstrated that moderate hypofractionated radiotherapy can be considered as a valid alternative strategy for localized prostate cancer. High-dose-rate brachytherapy can be administered according to different schedules. Proton beam radiotherapy represents a promising strategy, but further studies are needed to make it more affordable and accessible. At the moment, new technologies such as MRI-guided radiotherapy remain in early stages, but their potential abilities are very promising.

PO-1379 Moderate hypofractionated radiotherapy after prostatectomy in the context of the COVID19

PO-1379 Moderate hypofractionated radiotherapy after prostatectomy in the context of the COVID19

Moderately Hypofractionated Radiotherapy Without Chemotherapy in Elderly or Frail Patients With Head and Neck Cancer.

Comorbidity and frailty are relevant limitations of normofractionated combined radiochemotherapy for squamous cell head and neck cancer (HNSCC), especially in elderly patients. This retrospective study aimed to evaluate the efficacy and toxicity of moderately hypofractionated radiotherapy (HRT) without chemotherapy in patients ineligible for concurrent radiochemotherapy. Between 2011 and 2018, 51 elderly/frail patients with HNSCC were treated with either definitive (n=23) or adjuvant (n=28) moderate HRT. A dose of 45 Gy was given to the primary tumour region and cervical nodes with a sequential boost up to 50 in the adjuvant and 55 Gy in the definitive cure setting (2.5 Gy/fraction). Patient outcomes of locoregional control, overall survival, and acute and late toxicity were analysed. After a median follow-up of 6 months for the definitive HRT group and 28.5 months for the adjuvant HRT group, we found a median overall survival of 6 vs. 55 months (log-rank test: p<0.001) and a median locoregional control of 9 months vs. not reached (log-rank test: p=0.008), respectively. The 2-year rates of locoregional control were 28.5% for the definitive HRT group vs. 75.2% for the adjuvant HRT group. No acute or late grade 4-5 toxicity occurred; grade 3 toxicity was rarely documented. HRT in elderly/frail patients with HNSCC who are unfit for chemotherapy leads to acceptable local control with moderate toxicity in a short overall treatment time. Especially in the postoperative situation, HRT can be considered an appropriate alternative to normofractionated radio(chemo)therapy. Definitive HRT can be a treatment alternative, especially for multimorbid patients.

Ultrahypofractionated Radiotherapy versus Conventional to Moderate Hypofractionated Radiotherapy for Clinically Localized Prostate Cancer.

Simple SummaryRecently, shortening treatment time is becoming more important. Ultrahypofractionated radiotherapy (UHF) for localized prostate cancer is a fascinating treatment strategy; however, the concept of a well-balanced, optimal dose during UHF radiotherapy remains a contentious strategy, with only a few studies on UHF already reported. We must wait for the results of randomized trials several years away. Therefore, we tried to reveal the acceptable schedule in comparison to conventional to moderate hypofractionated radiotherapy so far. We found that UHF using EQD2 ≤ 100 Gy1.5 is a feasible UHF schedule with a good balance between toxicity and efficacy.The purpose of this study was to compare the toxicity (first endpoint) and efficacy (second endpoint) of ultrahypofractionated radiotherapy (UHF) and dose-escalated conventional to moderate hypofractionated radiotherapy (DeRT) for clinically localized prostate cancer. We compared 253 patients treated with UHF and 499 patients treated with DeRT using multi-institutional retrospective data. To analyze toxicity, we divided UHF into High-dose UHF (H-UHF; equivalent doses of 2 Gy per fraction: EQD2 > 100 Gy1.5) and low-dose UHF (L-UHF; EQD2 ≤ 100 Gy1.5). In toxicity, H-UHF elevated for 3 years accumulated late gastrointestinal and genitourinary toxicity grade ≥ 2 (11.1% and 9.3%) more than L-UHF (3% and 1.2%) and DeRT (3.1% and 4.8%, p = 0.00126 and p = 0.00549). With median follow-up periods of 32.0 and 61.7 months, the actuarial 3-year biochemical failure-free survival rates were 100% (100% and 100% in the L-UHF and H-UHF) and 96.3% in the low-risk group, 96.5% (97.1% and 95.6%) and 94.9% in the intermediate-risk group, and 93.7% (100% and 94.6%) and 91.7% in the high-risk group in the UHF and DeRT groups, respectively. UHF showed equivocal efficacy, although not conclusive but suggestive due to a short follow-up period of UHF. L-UHF using EQD2 ≤ 100 Gy1.5 is a feasible UHF schedule with a good balance between toxicity and efficacy.

P96 - Plan quality versus anatomic structure mutual disposition in moderate hypofractionated prostate radiotherapy

P96 - Plan quality versus anatomic structure mutual disposition in moderate hypofractionated prostate radiotherapy

P97 - Plan quality in moderate hypofractionated prostate radiotherapy: a tool to facilitate and standardize plan quality and consistency

P97 - Plan quality in moderate hypofractionated prostate radiotherapy: a tool to facilitate and standardize plan quality and consistency

PSMA-PET/MRI-Based Focal Dose Escalation in Patients with Primary Prostate Cancer Treated with Stereotactic Body Radiation Therapy (HypoFocal-SBRT): Study Protocol of a Randomized, Multicentric Phase III Trial.

Simple SummaryProstate cancer (PCa) is the most diagnosed malignancy of men worldwide, and radiotherapy (RT) is a main treatment option for patients in all disease stages. Modern diagnostic imaging and RT techniques enable an effective and safe delivery of high RT doses and a reduction of treatment time. We present a study protocol of a phase III trial implementing most modern imaging techniques and RT approaches. We compare the standard RT treatment with an RT concept of reduced treatment time and focal dose escalation based on the patient’s individual tumor morphology. This HypoFocal-SBRT trial aims to individualize treatment of PCa patients.Technical advances in radiotherapy (RT) treatment planning and delivery have substantially changed RT concepts for primary prostate cancer (PCa) by (i) enabling a reduction of treatment time, and by (ii) enabling safe delivery of high RT doses. Several studies proposed a dose–response relationship for patients with primary PCa and especially in patients with high-risk features, as dose escalation leads to improved tumor control. In parallel to the improvements in RT techniques, diagnostic imaging techniques like multiparametric magnetic resonance imaging (mpMRI) and positron-emission tomography targeting prostate-specific-membrane antigen (PSMA-PET) evolved and enable an accurate depiction of the intraprostatic tumor mass for the first time. The HypoFocal-SBRT study combines ultra-hypofractionated RT/stereotactic body RT, with focal RT dose escalation on intraprostatic tumor sides by applying state of the art diagnostic imaging and most modern RT concepts. This novel strategy will be compared with moderate hypofractionated RT (MHRT), one option for the curative primary treatment of PCa, which has been proven by several prospective trials and is recommended and carried out worldwide. We suspect an increase in relapse-free survival (RFS), and we will assess quality of life in order to detect potential changes.

Post-operative hypofractionated radiotherapy for prostate cancer: a mono-institutional analysis of toxicity and clinical outcomes.

As the use of hypofractionation has spread in the setting of curative prostate radiotherapy, few data are available in the post-operative scenario. This study reports a mono-institutional experience of moderate post-operative hypofractionated radiotherapy for prostate cancer. In February 2021, we retrospectively assessed the outcomes of 129 patients who received between April 2013 and May 2020 hypofractionated post-operative radiotherapy using Helical Tomotherapy. Toxicity was assessed using CTCAE criteria v4.0. Survival endpoints were calculated with Kaplan-Meier method. Median age and follow-up were, respectively, 67years and 43months. Adjuvant and salvage treatment were delivered to 63.5% and 36.4% of patients to a median total dose of 63.8Gy (61.6-65.25Gy) in 29 fractions (2.12-2.25Gy/fraction). Pelvic lymph-nodes irradiation was performed in 67.4% of cases. ADT was added in 50%. Acute toxicity was: G1 and G2 GU events in 36% and 9.3% of cases; G1 and G2 GI events in 29.4% and 13.9%. Late GU toxicity occurred in 12.4% of cases: 3.1% G1, 7.7% G2 and 1.5% G3 events; GI toxicity consisted of 1.5% G1 and 7.7% G2 events. Biochemical relapse occurred in 26.3% of cases, recording no significant differences between adjuvant and salvage (p = 0.67), with 4- and 5-years bRFS rates of 78.7% and 75.6%. Two patients died of progressive disease and eight for non-oncological causes resulting in 3-years overall survival and cancer-specific survival rates of 98% and 98.4%. Our experience supports the use of moderate hypofractionation for prostate bed radiotherapy, with minimal toxicity and promising results in terms of clinical outcomes.

Impact of Hypofractionated Radiotherapy on Patient-reported Outcomes in Prostate Cancer: Results up to 5 yr in the CHHiP trial (CRUK/06/016)

BackgroundModerate hypofractionation is the recommended standard of care for localised prostate cancer following the results of trials including Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy in Prostate Cancer (CHHiP). Evaluation of long-term patient-reported outcomes (PROs) is important to confirm safety and enhance patient information. ObjectiveTo determine whether 5-yr PROs from the CHHiP quality of life (QoL) substudy confirm 2-yr findings and assess patterns over follow-up. Design, setting, and participantsA phase III randomised controlled trial recruited from 2002 to 2011. The QoL substudy completed accrual in 2009; participants were followed up to 5 yr after radiotherapy. Analyses used data snapshot taken on August 26, 2016. A total of 71 radiotherapy centres were included in the study (UK, Republic of Ireland, Switzerland, and New Zealand); all 57 UK centres participated in the QoL substudy. CHHiP recruited 3216 men with localised prostate cancer (cT1b-T3aN0M0). InterventionConventional (74 Gy/37 fractions/7.4 wk) or hypofractionated radiotherapy (60 Gy/20 fractions/4 wk or 57 Gy/19 fractions/3.8 wk) was delivered with intensity-modulated techniques. Outcome measurements and statistical analysisUniversity of California Los Angeles Prostate Cancer Index, Short Form 36 and Functional Assessment of Cancer Therapy—Prostate, or Expanded Prostate Cancer Index Composite and Short Form 12 questionnaires were administered at baseline, before radiotherapy, at 10 wk, and at 6, 12, 18, 24, 36, 48, and 60 mo after radiotherapy. The QoL primary endpoint was overall bowel bother. Results and limitationsThe QoL substudy recruited 2100 patients; 1141 5-yr forms were available from 1957 patients still alive (58%). There were no statistically significant differences in 5-yr prevalence of overall “moderate or big” bowel bother: 19/349 (5.4%), 29/381 (7.6%), and 21/393 (5.3%) for 74, 60, and 57 Gy, respectively; overall urinary or sexual bother at 5 yr was similar between schedules. Bowel and urinary symptoms remained stable from 2 to 5 yr for all schedules. Some evidence of worsening overall sexual bother from baseline to 5 yr was less likely in the hypofractionated schedules compared with 74 Gy (odds ratios for increase in bother score vs 74 Gy: 0.55 [0.30–0.99], p = 0.009 for 60 Gy, and 0.52 [0.29–0.94], p = 0.004 for 57 Gy). General QoL scores were similar between schedules at 5 yr. ConclusionsLonger follow-up confirms earlier findings, with similar patient-reported bowel, urinary, and sexual problems between schedules overall. The continued low incidence of moderate or high bother confirms that moderate hypofractionation should be the standard of care for intermediate-risk localised prostate cancer. Patient summaryWe looked at patient-reported outcomes up to 5 yr after treatment in a trial of different radiotherapy schedules for prostate cancer. The findings confirmed that shorter radiotherapy schedules were as safe as standard radiotherapy in terms of bowel, urinary, and sexual problems. Take Home MessageBowel, urinary, and sexual symptoms were similar between schedules up to 5 yr. The continued low incidence of moderate/high bother confirms that moderate hypofractionated radiotherapy should be considered the standard of care for men with intermediate-risk prostate cancer.