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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. Because bilateral irradiation of the neck contributes to dysphagia, xerostomia and hypothyroidism in a dose dependent way, dose de-escalation to these regions can open a window of opportunity to reduce toxicity and improve quality of life after treatment.Methods: UPGRADE-RT is a multicenter, phase III, single-blinded, randomized controlled trial. Patients to be treated with definitive radiation therapy for a newly diagnosed stage T2-4 N0-2 M0 squamous cell carcinoma of the oropharynx, hypopharynx or larynx are eligible. Exclusion criteria are recurrent disease, oncologic surgery to the head and neck area, concomitant chemotherapy or epidermal growth factor receptor inhibitors. In total, 300 patients will be randomized in a 2:1 ratio to a treatment arm with or without de-escalation of the elective radiation dose and introduction of an intermediate dose-level for selected lymph nodes. Radiation therapy planning FDG-PET/CT-scans will be acquired to guide risk assessment of borderline-sized cervical nodes that can be treated with the intermediate dose level. Treatment will be given with intensity-modulated radiation therapy or volumetric arc therapy with simultaneous-integrated boost using an accelerated fractionation schedule, 33 fractions in 5 weeks. The primary endpoint is 'normalcy of diet' at 1 year after treatment (toxicity). The secondary endpoint is the actuarial rate of recurrence in electively irradiated lymph nodes at 2 years after treatment (safety).Discussion: The objective of the UPGRADE-RT trial is to investigate whether de-escalation of elective radiation dose and the introduction of an intermediate dose-level for borderline sized lymph nodes in the treatment of head and neck cancer will result in less radiation sequelae and improved quality of life after treatment without compromising the recurrence rate in the electively treated neck.Trial Registration: ClinicalTrials.gov Identifier: NCT02442375 . [ABSTRACT FROM AUTHOR]

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. These lymph nodes were identified and delineated on a radiotherapy planning CT to create a boost volume. Based on the location of the MRL-positive lymph nodes, the standard elective pelvic target volume was individualized. An IMRT plan with a simultaneous integrated boost (SIB) was created with dose prescriptions of 42 Gy to the pelvic target volume, a boost to 60 Gy to the MRL-positive lymph nodes, and 72 Gy to the prostate. Results: All MRL-positive lymph nodes could be identified on the planning CT. This information could be used to delineate a boost volume and to individualize the pelvic target volume for elective irradiation. IMRT planning delivered highly acceptable radiotherapy plans with regard to the prescribed dose levels and the dose to the organs at risk (OARs). Conclusion: MRL can be used to select patients with limited lymph node involvement for pelvic radiotherapy. MRL-guided delineation of a boost volume and an elective pelvic target volume for selective high-dose lymph node irradiation with IMRT is feasible. Whether this approach will result in improved outcome for these patients needs to be investigated in further clinical studies. [ABSTRACT FROM AUTHOR]

Abstract: 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. A method to analyze and visualize planning tradeoffs was developed and evaluated. Results: Lung and oesophagus were identified as the critical organs at risk for NSCLC, the sparing of which strongly influences PTV coverage. Systematically analyzing the tradeoffs between these organs revealed that the sparing of these organs was approximately linearly related to PTV coverage parameters. Using this property, a tool was developed to graphically present the tradeoffs between the sparing of these organs at risk and the PTV coverage. The tool is an effective method to visualize the tradeoffs. Conclusions: A tool was developed to assist IMRT plan design and selection. The clear presentation of the tradeoffs between OAR dose and coverage facilitates the optimization process and offers additional information to the clinician for a patient specific choice of the optimal IMRT plan. [Copyright &y& Elsevier]

• A higher radiation dose to the anorectum is associated with increased overall GI toxicity. • Increasing the dose to the anorectum should be weighed against the benefit of focal dose escalation. • Further increasing the dose to the tumor without increasing the anorectal dose should be explored. 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). All patients in the FLAME trial were analyzed, irrespective of treatment arm. The dose–effect relation of the anorectal dose parameters (D2cm3 and D50%) and GI toxicity grade ≥2 in four years of follow-up was assessed using a mixed model analysis for repeated measurements, adjusted for age, cardiovascular disease, diabetes mellitus, T-stage, baseline toxicity grade ≥1, hormonal therapy and institute. A dose–effect relation for D2cm3 and D50% was observed with adjusted odds ratios of 1.17 (95% CI 1.13–1.21, p < 0.0001) and 1.20 (95% CI 1.14–1.25, p < 0.0001) for GI toxicity, respectively. Although there was no difference in toxicity between study arms, a higher radiation dose to the anorectum was associated with a statistically significant increase in GI toxicity following EBRT for prostate cancer. This dose–effect relation was present for both large and small anorectal volumes. Therefore, further increase in dose to the anorectum should be weighed against the benefit of focal dose escalation for prostate cancer. [ABSTRACT FROM AUTHOR]

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.Methods and Materials: We derived dose-volume parameters from planned dose distributions of 539 FLAME trial patients in 4 institutions and compared them between both arms. In the dose-escalated arm, we determined overlap volume histograms and derived features representing patient anatomy. We predicted tumor D98% with a linear regression on anatomic features and performed replanning on 21 plans.Results: In the dose-escalated arm, the median tumor D50% and D98% were 93.0 and 84.7 Gy, and 99% of the tumors had a dose escalation greater than 82.4 Gy (107% of 77 Gy). In both arms organs at risk constraints were met. Five out of 73 anatomic features were found to be predictive for tumor D98%. Median predicted tumor D98% was 4.4 Gy higher than planned D98%. Upon replanning, median tumor D98% increased by 3.0 Gy. A strong correlation between predicted increase in D98% and realized increase upon replanning was found (ρ = 0.86).Conclusions: Focal dose escalation in prostate cancer was feasible with a dose escalation to 99% of the tumors. Replanning resulted in an increased tumor dose that correlated well with the prediction model. The model was able to identify tumors on which a higher boost dose could be planned. The model has potential as a quality assessment tool in focal dose escalated treatment plans. [ABSTRACT FROM AUTHOR]

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). A dose of 39.6 Gy in 22 daily fractions of 1.8 Gy was prescribed. Dose–volume parameters for target volumes and OARs were compared for the two techniques. Results: The maximum dose with IMRT was <107% in all patients. V<95 and V>107 were <1 cm3 for IMRT compared with 3–9 cm3 for the craniospinal and 26–43 cm3 for the spinal–spinal junction with 3DCRT. These observations corresponded with a lower homogeneity index and a higher conformity index for the spinal planning target volume with IMRT. IMRT provided considerable sparing of acute and late reacting tissues. V75 for the esophagus, gastroesophageal junction, and intestine was 81%, 81%, and 22% with 3DCRT versus 5%, 0%, and 1% with IMRT, respectively. V75 for the heart and thyroid was 42% and 32% vs. 0% with IMRT. Conclusion: IMRT with daily intrafractionally modulated junction results in a superior target coverage and junction homogeneity compared with 3DCRT. A significant dose reduction can be obtained for acute as well as late-reacting tissues. [Copyright &y& Elsevier]

Abstract: 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. Furthermore, the Awall and Rwall were delineated. In both the scans, IMRT plans were generated with a prescribed dose of 70Gy. The mean dose (D mean), maximum dose, minimum dose, and volumes exposed to doses ranging from ⩾20 to ⩾70Gy (V 20–V 70) to the Awall and Rwall were calculated. Finally, inner Rwall surface areas exposed to doses ranging from ⩾20 to ⩾70Gy (A 20–A 70) were calculated. Dose-parameters were compared between plans with and without ERB. Results: All Awall parameters, except V 70, were significantly reduced by the ERB with an overall D mean reduction of 6Gy. Absolute reductions in dose–volume parameters varied from 5% to 11%. Significantly reduced Rwall V 30, V 40, and A 40 were observed with ERB, irrespective of the target volume size. Conclusion: ERB application significantly reduces Awall and to a lesser degree Rwall doses in high-dose post-prostatectomy IMRT. [Copyright &y& Elsevier]

Abstract: 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. Three-field and 4-field 3D-CRT plans, and IMRT plans were generated with a prescription dose of 78Gy. In 144 treatment plans, the minimum dose (D min), maximum dose (D max), and mean dose (D mean) to the Awall were calculated, as well as the Awall volumes exposed to doses ranging from ⩾20Gy to ⩾70Gy (V 20 − V 70, respectively). Results: In the 3D-CRT plans, an ERB significantly reduced D mean, D max, and V 30 − V 70. For IMRT all investigated dose parameters were significantly reduced by the ERB. The absolute reduction of D mean was 12Gy in 3D-CRT and was 7.5Gy in IMRT for both methods of Awall delineation. Conclusions: Application of an ERB showed a significant Awall sparing effect in both 3D-CRT and IMRT. This may lead to reduced late anal toxicity in prostate radiotherapy. [Copyright &y& Elsevier]