Stereotactic body radiotherapy with a focal boost to the intraprostatic tumor for intermediate and high risk prostate cancer: 5-year efficacy and toxicity in the hypo-FLAME trial.

Background: The addition of an integrated focal boost to the intraprostatic lesion is associated with improved biochemical disease-free survival (bDFS) in patients with intermediate- and high-risk prostate cancer (PCa) in conventionally fractionated radiotherapy. Furthermore, whole gland stereotactic body radiotherapy (SBRT) demonstrated to be non-inferior to conventional radiotherapy for low- and intermediate-risk PCa. To investigate the combination of ultra-hypofractionated prostate SBRT with iso-toxic focal boosting for intermediate- and high-risk PCa, we performed the hypo-FLAME trial.

From once-weekly to semi-weekly whole prostate gland stereotactic radiotherapy with focal boosting: Primary endpoint analysis of the multicenter phase II hypo-FLAME 2.0 trial.

Background And Purpose: The hypo-FLAME trial showed that once-weekly (QW) focal boosted prostate stereotactic body radiotherapy (SBRT) is associated with acceptable acute genitourinary (GU) and gastrointestinal (GI) toxicity. Currently, we investigated the safety of reducing the overall treatment time (OTT) of focal boosted prostate SBRT from 29 to 15 days.

Material And Methods: Patients with intermediate- and high-risk prostate cancer were treated with SBRT delivering 35 Gy in 5 fractions to the whole prostate gland with an iso-toxic boost up to 50 Gy to the intraprostatic lesion(s) in a semi-weekly (BIW) schedule.

Urethral and bladder dose-effect relations for late genitourinary toxicity following external beam radiotherapy for prostate cancer in the FLAME trial.

Purpose Or Objectives: The FLAME trial (NCT01168479) showed that by adding a focal boost to conventional fractionated EBRT in the treatment of localized prostate cancer, the five-year biochemical disease-free survival increased, without significantly increasing toxicity. The aim of the present study was to investigate the association between radiation dose to the bladder and urethra and genitourinary (GU) toxicity grade ≥2 in the entire cohort.

Material And Methods: The dose-effect relations of the urethra and bladder dose, separately, and GU toxicity grade ≥2 (CTCAE 3.

Patterns of Failure Following External Beam Radiotherapy With or Without an Additional Focal Boost in the Randomized Controlled FLAME Trial for Localized Prostate Cancer.

Background: Focal dose escalation in external beam radiotherapy (EBRT) showed an increase in 5-yr biochemical disease-free survival in the Focal Lesion Ablative Microboost in Prostate Cancer (FLAME) trial.

Objective: To analyze the effect of a focal boost to intraprostatic lesions on local failure-free survival (LFS) and regional + distant metastasis-free survival (rdMFS).

Design, Setting, And Participants: Patients with intermediate- or high-risk localized prostate cancer were included in FLAME, a phase 3, multicenter, randomized controlled trial.

Anorectal dose-effect relations for late gastrointestinal toxicity following external beam radiotherapy for prostate cancer in the FLAME trial.

Background And Purpose: The phase III FLAME trial (NCT01168479) showed an increase in five-year biochemical disease-free survival, with no significant increase in toxicity when adding a focal boost to external beam radiotherapy (EBRT) for localized prostate cancer [Kerkmeijer et al. JCO 2021]. The aim of this study was to investigate the association between delivered radiation dose to the anorectum and gastrointestinal (GI) toxicity (grade ≥2).

Ga-PSMA-11 PET, F-PSMA-1007 PET, and MRI for Gross Tumor Volume Delineation in Primary Prostate Cancer: Intermodality and Intertracer Variability.

Purpose: To assess the intermodality and intertracer variability of gallium-68 (Ga)- or fluorine-18 (F)-labeled prostate-specific membrane antigen (PSMA) positron emission tomography (PET) and biparametric magnetic resonance imaging (bpMRI)-based gross tumor volume (GTV) delineation for focal boosting in primary prostate cancer.

Methods: Nineteen prospectively enrolled patients with prostate cancer underwent a PSMA PET/MRI scan, divided into a 1:1 ratio between Ga-PSMA-11 and F-PSMA-1007, before radical prostatectomy (IWT140193). Four delineation teams performed manual contouring of the GTV based on bpMRI and PSMA PET imaging, separately.

Focal Boost to the Intraprostatic Tumor in External Beam Radiotherapy for Patients With Localized Prostate Cancer: Results From the FLAME Randomized Phase III Trial.

Purpose: This study investigates whether focal boosting of the macroscopic visible tumor with external beam radiotherapy increases biochemical disease-free survival (bDFS) in patients with localized prostate cancer.

Patients And Methods: In the phase III, multicenter, randomized controlled Focal Lesion Ablative Microboost in Prostate Cancer trial, 571 patients with intermediate- and high-risk prostate cancer were enrolled between 2009 and 2015. Patients assigned to standard treatment received 77 Gy (fractions of 2.

Optimal Ga-PSMA and F-PSMA PET window levelling for gross tumour volume delineation in primary prostate cancer.

Purpose: This study proposes optimal tracer-specific threshold-based window levels for PSMA PET-based intraprostatic gross tumour volume (GTV) contouring to reduce interobserver delineation variability.

Methods: Nine Ga-PSMA-11 and nine F-PSMA-1007 PET scans including GTV delineations of four expert teams (GTV) and a majority-voted GTV (GTV) were assessed with respect to a registered histopathological GTV (GTV) as the gold standard reference. The standard uptake values (SUVs) per voxel were converted to a percentage (SUV%) relative to the SUV.

Knowledge-Based Assessment of Focal Dose Escalation Treatment Plans in Prostate Cancer.

Purpose: In a randomized focal dose escalation radiation therapy trial for prostate cancer (FLAME), up to 95 Gy was prescribed to the tumor in the dose-escalated arm, with 77 Gy to the entire prostate in both arms. As dose constraints to organs at risk had priority over dose escalation and suboptimal planning could occur, we investigated how well the dose to the tumor was boosted. We developed an anatomy-based prediction model to identify plans with suboptimal tumor dose and performed replanning to validate our model.

Primary endpoint analysis of the multicentre phase II hypo-FLAME trial for intermediate and high risk prostate cancer.

Background And Purpose: Local recurrences after radiotherapy for prostate cancer (PCa) often originate at the location of the macroscopic tumour(s). Since PCa cells are known to be sensitive to high fraction doses, hypofractionated whole gland stereotactic body radiotherapy (SBRT) in conjunction with a simultaneous ablative microboost to the macroscopic tumour(s) within the prostate could be a way to reduce the risk of local failure. We investigated the safety of this treatment strategy.

Planning feasibility of extremely hypofractionated prostate radiotherapy on a 1.5 T magnetic resonance imaging guided linear accelerator.

Background And Purpose: Recently, intermediate and high-risk prostate cancer patients have been treated in a multicenter phase II trial with extremely hypofractionated prostate radiotherapy (hypo-FLAME trial). The purpose of the current study was to investigate whether a 1.5 T magnetic resonance imaging guided linear accelerator (MRI-linac) could achieve complex dose distributions of a quality similar to conventional linac state-of-the-art prostate treatments.

Stereotactic body radiation therapy with optional focal lesion ablative microboost in prostate cancer: Topical review and multicenter consensus.

Stereotactic body radiotherapy (SBRT) for prostate cancer (PCa) is gaining interest by the recent publication of the first phase III trials on prostate SBRT and the promising results of many other phase II trials. Before long term results became available, the major concern for implementing SBRT in PCa in daily clinical practice was the potential risk of late genitourinary (GU) and gastrointestinal (GI) toxicity. A number of recently published trials, including late outcome and toxicity data, contributed to the growing evidence for implementation of SBRT for PCa in daily clinical practice.

Uniform FDG-PET guided GRAdient Dose prEscription to reduce late Radiation Toxicity (UPGRADE-RT): study protocol for a randomized clinical trial with dose reduction to the elective neck in head and neck squamous cell carcinoma.

Background: In definitive radiation therapy for head and neck cancer, clinically uninvolved cervical lymph nodes are irradiated with a so-called 'elective dose' in order to achieve control of clinically occult metastases. As a consequence of high-resolution diagnostic imaging, occult tumor volume has significantly decreased in the last decades. Since the elective dose is dependent on occult tumor volume, the currently used elective dose may be higher than necessary.

Cross-institutional knowledge-based planning (KBP) implementation and its performance comparison to Auto-Planning Engine (APE).

Background And Purpose: To investigate (1) whether a plan library established at one institution can be applied for another institution's knowledge-based planning (KBP); (2) the performance of cross-institutional KBP compared to Auto-Planning Engine (APE).

Material And Methods: Radboud University Medical Center (RUMC) provided 35 oropharyngeal cancer patients (68Gy to PTV and 50.3Gy to PTV) with clinically-delivered and comparative APE plans.

Multi-institutional comparison of volumetric modulated arc therapy vs. intensity-modulated radiation therapy for head-and-neck cancer: a planning study.

Background: Compared to static beam Intensity-Modulated Radiation Therapy (IMRT), the main advantage of Volumetric Modulated Arc Therapy (VMAT) is a shortened delivery time, which leads to improved patient comfort and possibly smaller intra-fraction movements. This study aims at a treatment planner-independent comparison of radiotherapy treatment planning of IMRT and VMAT for head-and-neck cancer performed by several institutes and based on the same CT- and contouring data.

Methods: Five institutes generated IMRT and VMAT plans for five oropharyngeal cancer patients using either Pinnacle3 or Oncentra Masterplan to be delivered on Elekta linear accelerators.

High incidence of implantable cardioverter defibrillator malfunctions during radiation therapy: neutrons as a probable cause of soft errors.

Aims: To investigate the behaviour of the implantable cardioverter defibrillator (ICD) function during actual radiotherapy sessions.

Methods And Results: Fifteen patients with an ICD underwent 17 radiation treatments for cancer [cumulative dose to the tumour was between 16 Gray (Gy) and 70 Gy; photon beams with maximum energies between 6 megaelectronvolt (MeV) and 18 MeV were employed]. During every session, the ICD was programmed to a monitoring mode to prevent inappropriate therapy delivery.

Endorectal balloon reduces anorectal doses in post-prostatectomy intensity-modulated radiotherapy.

Background And Purpose: To investigate the effect of an endorectal balloon (ERB) on anal wall (Awall) and rectal wall (Rwall) doses in high-dose post-prostatectomy intensity-modulated radiotherapy (IMRT).

Materials And Methods: For 20 patients, referred for salvage IMRT after prostatectomy for prostate cancer, two planning CT-scans were performed: one with and one without an air-filled ERB. A planning target volume (PTV) was defined, using international guidelines.

Optimal normal tissue sparing in craniospinal axis irradiation using IMRT with daily intrafractionally modulated junction(s).

Purpose: To develop a treatment technique for craniospinal irradiation using intensity-modulated radiotherapy (IMRT) with improved dose homogeneity at the field junction(s), increased target volume conformity, and minimized dose to the organs at risk (OARs).

Methods And Materials: Five patients with high-risk medulloblastoma underwent CT simulation in supine position. For each patient, an IMRT plan with daily intrafractionally modulated junction(s) was generated, as well as a treatment plan based on conventional three-dimensional planning (3DCRT).

Magnetic resonance lymphography-guided selective high-dose lymph node irradiation in prostate cancer.

Purpose: To demonstrate the feasibility of magnetic resonance lymphography (MRL) -guided delineation of a boost volume and an elective target volume for pelvic lymph node irradiation in patients with prostate cancer. The feasibility of irradiating these volumes with a high-dose boost to the MRL-positive lymph nodes in conjunction with irradiation of the prostate using intensity-modulated radiotherapy (IMRT) was also investigated.

Methods And Materials: In 4 prostate cancer patients with a high risk of lymph node involvement but no enlarged lymph nodes on CT and/or MRI, MRL detected pathological lymph nodes in the pelvis.

A practical approach to assess clinical planning tradeoffs in the design of individualized IMRT treatment plans.

Background And Purpose: To investigate the tradeoffs between organ at risk sparing and tumour coverage for IMRT treatment of lung tumours, and to develop a tool for clinical use to graphically represent these tradeoffs.

Material And Methods: For 5 patients with inoperable non-small cell lung cancer (NSCLC) different IMRT plans were generated using a standard TPS. The plans were automatically generated for a range of IMRT settings (weights and dose levels of the objective functions) and were systematically evaluated, focusing on the tradeoffs between organ at risk (OAR) dose and target coverage.

Anal wall sparing effect of an endorectal balloon in 3D conformal and intensity-modulated prostate radiotherapy.

Background And Purpose: To investigate the anal wall (Awall) sparing effect of an endorectal balloon (ERB) in 3D conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) for prostate cancer.

Materials And Methods: In 24 patients with localized prostate carcinoma, two planning CT-scans were performed: with and without ERB. A prostate planning target volume (PTV) was defined, and the Awall was delineated, using two different methods.