High-dose Planning Target Volume Research Articles

Dose averaged linear energy transfer optimization for large sacral chordomas in carbon ion therapy.

Carbon ion beams are well accepted as densely ionizing radiation with a high linear energy transfer (LET). However, the current clinical practice does not fully exploit the highest possible dose-averaged LET (LETd) and, consequently, the biological potential in the target. This aspect becomes worse in larger tumors for which inferior clinical outcomes and corresponding lower LETd wasreported. The vicinity to critical organs in general and the inferior overall survival reported for larger sacral chordomas treated with carbon ion radiotherapy (CIRT), makes the treatment of such tumors challenging. In this work it was aimed to increase the LETd in large volume tumors while maintaining the relative biological effectiveness (RBE)-weighted dose, utilizing the LETd optimization functions of a commercial treatment planning system (TPS). Ten reference sequential boost carbon ion treatment plans, designed to mimic clinical plans for large sacral chordoma tumors, were generated. High dose clinical target volumes (CTV-HD) larger than were considered as large targets. The total RBE-weighted median dose prescription with the local effect model (LEM) was in 16 fractions (nine to low dose and seven to high dose planning target volume). No LETd optimization was performed in the reference plans, while LETd optimized plans used the minimum LETd (Lmin) optimization function in RayStation2023B. Three different Lmin values were investigated and specified for the seven boost fractions: , and . To compare the LETd optimized against reference plans, LETd and RBE-weighted dose based goals similar to and less strict than clinical ones were specified for the target. The goals for the organs at risk (OAR) remained unchanged. Robustness evaluation was studied for eight scenarios ( range uncertainty and setup uncertainty along the main three axes). The optimization method with resulted in an optimal LETd distribution with an average increase of (and ) in the CTV-HD by ( ) (and ( )), without significant difference in the RBE-weighted dose. By allowing over- and under-dosage in the target, the (and ) can be increased by ( ) (and ( )), using the optimization parameters . The pass rate for the OAR goals in the LETd optimized plans was in the same level as the reference plans. LETd optimization lead to less robust plans compared to referenceplans. Compared to conventionally optimized treatment plans, the LETd in the target was increased while maintaining the RBE-weighted dose using TPS LETd optimization functionalities. Regularly assessing RBE-weighted dose robustness and acquiring more in-room images remain crucial and inevitable aspects duringtreatment.

Radiotherapy quality assurance in the TROG 12.01 randomised trial and its impact on loco-regional failure.

There is no consensus as to what specifically constitutes head and neck cancer radiotherapy quality assurance (HNC RT QA). The aims of this study are to (1) describe the RT QA processes used in the TROG 12.01 study, (2) review the RT QA processes undertaken for all patients with loco-regional failure (LRF), and (3) provide prospective data to propose a consensus statement regarding the minimal components and optimal timing of HNC RT QA. All patients undergoing RT QA in the original TROG 12.01 study were included in this substudy. All participating sites completed IMRT credentialling and a clinical benchmark case. Real-time (pre-treatment) RT QA was performed for the first patient of each treating radiation oncologist, and for one in five of subsequent patients. Protocol violations were deemed major if they related to contour and/or dose of gross tumour volume (GTV), high dose planning target volume (PTVhd), or critical organs of risk (spinal cord, mandible, and brachial plexus). Thirty HNROs from 15 institutions accrued 182 patients. There were 28 clinical benchmark cases, 27 pre-treatment RT QA cases, and 38 post-treatment cases. Comprehensive RT QA was performed in 65/182 (36%) treated patients. Major protocol violations were found in 5/28 benchmark cases, 5/27 pre-treatment cases, and 6/38 post-treatment cases. An independent review of all nine LRF cases showed major protocol violations in four of nine cases. Only pre-treatment RT QA can improve patient outcomes. The minimal components of RT QA in HNC are GTVs, PTVhd, and critical organs at risk. What constitutes major dosimetric violations needs to be harmonised.

Head and neck radiotherapy quality assurance conference for dedicated review of delineated targets and organs at risk: results of a prospective study.

Head and neck (HN) radiotherapy (RT) is complex, involving multiple target and organ at risk (OAR) structures delineated by the radiation oncologist. Site-agnostic peer review after RT plan completion is often inadequate for thorough review of these structures. In-depth review of RT contours is critical to maintain high-quality RT and optimal patient outcomes. In August 2020, the HN RT Quality Assurance Conference, a weekly teleconference that included at least one radiation oncology HN specialist, was activated at our institution. Targets and OARs were reviewed in detail prior to RT plan creation. A parallel implementation study recorded patient factors and outcomes of these reviews. A major change was any modification to the high-dose planning target volume (PTV) or the prescription dose/fractionation; a minor change was modification to the intermediate-dose PTV, low-dose PTV, or any OAR. We analysed the results of consecutive RT contour review in the first 20 months since its initiation. A total of 208 patients treated by 8 providers were reviewed: 86·5% from the primary tertiary care hospital and 13·5% from regional practices. A major change was recommended in 14·4% and implemented in 25 of 30 cases (83·3%). A minor change was recommended in 17·3% and implemented in 32 of 36 cases (88·9%). A survey of participants found that all (n = 11) strongly agreed or agreed that the conference was useful. Dedicated review of RT targets/OARs with a HN subspecialist is associated with substantial rates of suggested and implemented modifications to the contours.

Implementation of a Dedicated Head and Neck Radiotherapy Peer Review Conference: Results of a Prospective Study

<h3>Purpose/Objective(s)</h3> Head and neck radiotherapy (RT) is complex, involving multiple targets and organs at risk (OARs). Routine RT plan peer review is often inadequate for thorough review of the head and neck targets and OARs. <h3>Materials/Methods</h3> Patients treated between August 2020 and December 2021 were evaluated in a weekly structured head and neck RT plan peer review conference including at least one head and neck RT subspecialist. All plans were initially reviewed by the treating faculty member prior to presentation in contour review conference. Patient and disease factors were recorded, as were the results of the peer review discussion, including the number and nature of recommended RT plan modifications and the rate of implementation. A major change was defined as any modification to the high-dose planning target volume (PTV) or RT prescription or fractionation. A minor change was defined as modification to at least one of the intermediate-dose PTV, low-dose PTV, or any OAR. <h3>Results</h3> 186 patients treated by 8 individual providers were prospectively recorded, 86.6% from the main site and 13.4% from 3 regional practices. The most common primary sites were oropharynx (29.6%), oral cavity (22%), cutaneous (16.7%), larynx/hypopharynx (16.1%). T3-4 disease was present in 68.3%, N2-3 in 37.6%. RT intent was definitive (44.6%), postoperative (49.5%), preoperative (1.6%), or palliative (4.3%). A major change was recommended in 14.5% (18 high-dose PTV, 7 prescription, 1 high-dose PTV and prescription) and implemented in 21 of 26 cases (80.8%). A minor change was recommended in 18.8% (20 low-dose PTV, 10 intermediate-dose PTV, 2 intermediate and low-dose PTV, 2 OAR, and 1 low-dose PTV and OAR) and implemented in 29 of 32 cases (90.6%). Additional workup was suggested in 2 cases (1.1%; 1 imaging study and 1 procedure) and was completed in both cases. Correction of plan changes was associated with a statistically significant delay of 1 day in overall treatment planning (p = 0.001). <h3>Conclusion</h3> A dedicated peer review conference for head and neck RT plans is feasible and well-accepted by providers. Peer review with structured review of head and neck RT contour volumes is associated with substantial rates of suggested and implemented modifications to the plan with minimal treatment delay.

Assessment of CBCT-based synthetic CT generation accuracy for adaptive radiotherapy planning.

Cone-beam CT (CBCT)-based synthetic CT (sCT) dose calculation has the potential to make the adaptive radiotherapy (ART) pathway more efficient while removing subjectivity. This study assessed four sCT generation methods using 15 head-and-neck rescanned ART patients. Each patient's planning CT (pCT), rescan CT (rCT), and CBCT post-rCT was acquired with the CBCT deformably registered to the rCT (dCBCT). The four methods investigated were as follows: method 1-deformably registering the pCT to the dCBCT. Method 2-assigning six mass density values to the dCBCT. Method 3-iteratively removing artifacts and correcting the dCBCT Hounsfield units (HU). Method 4-using a cycle general adversarial network machine learning model (trained with 45 paired pCT and CBCT). Treatment plans were created on the rCT and recalculated on each sCT. Planning target volume (PTV) and organ-at-risk (OAR) structures were contoured by clinicians on the rCT (high-dose PTV, low-dose PTV, spinal canal, larynx, brainstem, and parotids) to allow the assessment of dose-volume histogram statistics at clinically relevant points. The HU mean absolute error (MAE) and minimum dose gamma index pass rate (2%/2mm) were calculated, and the generation time was measured for 15 patients using the rCT as the comparator. For methods 1-4 the MAE, gamma index analysis, and generation time were as follows: 59.7HU, 100.0%, and 143s; 164.2HU, 95.2%, and 232s; 75.7HU, 99.9%, and 153s; and 79.4HU, 99.8%, and 112s, respectively. Dose differences for PTVs and OARs were all <0.3Gy except for method 2 (<0.5Gy). All methods were considered clinically viable. The machine learning method was found to be most suitable for clinical implementation due to its high dosimetric accuracy and short generation time. Further investigation is required for larger anatomical changes between the CBCT and pCT and for other anatomical sites.

Implementation of a dedicated head and neck radiotherapy peer review conference: results of a prospective study

Background Head and neck radiotherapy (RT) is complex, involving multiple targets and organs at risk (OARs). Routine RT plan peer review is often inadequate for thorough review of the head and neck targets and OARs. Methods Patients treated between August 2020 and December 2021 were evaluated in a weekly structured head and neck RT plan peer review conference including at least one head and neck RT subspecialist. Patient and disease factors were recorded, as were the results of the peer review discussion, including the number and nature of recommended RT plan modifications and the rate of implementation. A major change was defined as any modification to the high-dose planning target volume (PTV) or RT prescription or fractionation. A minor change was defined as modification to at least one of the intermediate-dose PTV, low-dose PTV, or any OAR. Results 186 patients treated by 8 individual providers were prospectively recorded, 86.6% from the main site and 13.4% from 3 regional practices. The most common primary sites were oropharynx (29.6%), oral cavity (22%), cutaneous (16.7%), larynx/hypopharynx (16.1%). T3-4 disease was present in 68.3%, N2-3 in 37.6%. RT intent was definitive (44.6%), postoperative (49.5%), preoperative (1.6%), or palliative (4.3%). A major change was recommended in 14.5% (18 high-dose PTV, 7 prescription, 1 high-dose PTV and prescription) and implemented in 21 of 26 cases (80.8%). A minor change was recommended in 18.8% (20 low-dose PTV, 10 intermediate-dose PTV, 2 intermediate and low-dose PTV, 2 OAR, and 1 low-dose PTV and OAR) and implemented in 29 of 32 cases (90.6%). Additional workup was suggested in 2 cases (1.1%; 1 imaging study and 1 procedure) and was completed in both cases. Correction of plan changes was associated with a statistically significant delay of 1 day in overall treatment planning (p = 0.001). Discussion A dedicated peer review conference for head and neck RT plans is feasible and well-accepted by providers. Peer review with structured review of head and neck RT contour volumes is associated with substantial rates of suggested and implemented modifications to the plan with minimal treatment delay. Head and neck radiotherapy (RT) is complex, involving multiple targets and organs at risk (OARs). Routine RT plan peer review is often inadequate for thorough review of the head and neck targets and OARs. Patients treated between August 2020 and December 2021 were evaluated in a weekly structured head and neck RT plan peer review conference including at least one head and neck RT subspecialist. Patient and disease factors were recorded, as were the results of the peer review discussion, including the number and nature of recommended RT plan modifications and the rate of implementation. A major change was defined as any modification to the high-dose planning target volume (PTV) or RT prescription or fractionation. A minor change was defined as modification to at least one of the intermediate-dose PTV, low-dose PTV, or any OAR. 186 patients treated by 8 individual providers were prospectively recorded, 86.6% from the main site and 13.4% from 3 regional practices. The most common primary sites were oropharynx (29.6%), oral cavity (22%), cutaneous (16.7%), larynx/hypopharynx (16.1%). T3-4 disease was present in 68.3%, N2-3 in 37.6%. RT intent was definitive (44.6%), postoperative (49.5%), preoperative (1.6%), or palliative (4.3%). A major change was recommended in 14.5% (18 high-dose PTV, 7 prescription, 1 high-dose PTV and prescription) and implemented in 21 of 26 cases (80.8%). A minor change was recommended in 18.8% (20 low-dose PTV, 10 intermediate-dose PTV, 2 intermediate and low-dose PTV, 2 OAR, and 1 low-dose PTV and OAR) and implemented in 29 of 32 cases (90.6%). Additional workup was suggested in 2 cases (1.1%; 1 imaging study and 1 procedure) and was completed in both cases. Correction of plan changes was associated with a statistically significant delay of 1 day in overall treatment planning (p = 0.001). A dedicated peer review conference for head and neck RT plans is feasible and well-accepted by providers. Peer review with structured review of head and neck RT contour volumes is associated with substantial rates of suggested and implemented modifications to the plan with minimal treatment delay.

Comparing Outcomes of Oligometastases Treated with Hypofractionated Image-Guided Radiotherapy (HIGRT) with a Simultaneous Integrated Boost (SIB) Technique versus Metastasis Alone: A Multi-Institutional Analysis.

Simple SummaryHypofractionated image-guided radiotherapy (HIGRT) is a common method in which high doses of radiation are delivered to treat oligometastatic disease. We have previously reported on the clinical outcomes of treating oligometastases with radiation using an elective simultaneous integrated boost technique (SIB), delivering higher doses to known metastases and reduced doses to adjacent bone or nodal basins. Here we compare outcomes of oligometastases receiving radiation targeting metastases alone (MA) versus those treated via an SIB. Both SIB and MA irradiation of oligometastases achieved high rates of tumor metastases control and similar pain control. Further investigation of this technique with prospective trials is warranted.Purpose: We previously reported on the clinical outcomes of treating oligometastases with radiation using an elective simultaneous integrated boost technique (SIB), delivering higher doses to known metastases and reduced doses to adjacent bone or nodal basins. Here we compare outcomes of oligometastases receiving radiation targeting metastases alone (MA) versus those treated via an SIB. Methods: Oligometastatic patients with ≤5 active metastases treated with either SIB or MA radiation at two institutions from 2013 to 2019 were analyzed retrospectively for treatment-related toxicity, pain control, and recurrence patterns. Tumor metastasis control (TMC) was defined as an absence of progression in the high dose planning target volume (PTV). Marginal recurrence (MR) was defined as recurrence outside the elective PTV but within the adjacent bone or nodal basin. Distant recurrence (DR) was defined as any recurrence that is not within the PTV or surrounding bone or nodal basin. The outcome rates were estimated using the Kaplan–Meier method and compared between the two techniques using the log-rank test. Results: 101 patients were treated via an SIB to 90 sites (58% nodal and 42% osseous) and via MA radiation to 46 sites (22% nodal and 78% osseous). The median follow-up among surviving patients was 24.6 months (range 1.4–71.0). Of the patients treated to MA, the doses ranged from 18 Gy in one fraction (22%) to 50 Gy in 10 fractions (50%). Most patients treated with an SIB received 50 Gy to the treated metastases and 30 Gy to the elective PTV in 10 fractions (88%). No acute grade ≥3 toxicities occurred in either cohort. Late grade ≥3 toxicity occurred in 3 SIB patients (vocal cord paralysis and two vertebral body compression), all related to the high dose PTV and not the elective volume. There was similar crude pain relief between cohorts. The MR-free survival rate at 2 years was 87% (95% CI: 70%, 95%) in the MA group and 98% (95% CI: 87%, 99%) in the SIB group (p = 0.07). The crude TMC was 89% (41/46) in the MA group and 94% (85/90) in the SIB group. There were no significant differences in DR-free survival (65% (95% CI: 55–74%; p = 0.24)), disease-free survival (60% (95% CI: 40–75%; p = 0.40)), or overall survival (88% (95% CI: 73–95%; p = 0.26)), between the MA and SIB cohorts. Conclusion: Both SIB and MA irradiation of oligometastases achieved high rates of TMC and similar pain control, with a trend towards improved MR-free survival for oligometastases treated with an SIB. Further investigation of this technique with prospective trials is warranted.

Assessment of Dose Accuracy for MR-Guided Online Adaptive Radiotherapy for Nasopharyngeal Carcinoma

MR-guided radiotherapy relies on the daily assignment of a relative electron density (rED) map to acquire the fraction specific dose calculation. The approach to acquire the rED map is used bulk rED assignment based on the rED values of the delineated region of interests (ROIs) to generate a synthetic CT (sCT). This study aims to evaluate the dose accuracy of this approach for application in 1.5 T MR-Linac, to assess the reliability of this approach in the case of online adaptive MR-guided radiotherapy for Nasopharyngeal Carcinoma (NPC) patients.The original CT and MRI T2 were acquired for 10 NPC patients and targets, organs at risk (OARs), bone and air regions were delineated on original CT in a treatment planning software. Each patient's MRI/CT image pair was aligned using a rigid registration algorithm, and the contours were copied to MRI from original CT. The sCT was then generated in MRI using bulk rED assignment approach, based on the rED values of the delineated region of interests (ROIs). Three different types of sCT images were generated: The sCTICRU uses the rED values recommended by ICRU46, the sCTtailor uses the patient-specific mean rED values, and the sCTHomogeneity was created using water equivalent value of 1 g/cm3 for entire patient data set. The same treatment plan was calculated on three sCTs and original CT. The dose calculation accuracy was investigated in terms of gamma analysis, point dose comparison and dose volume histogram (DVH) parameters.For both criteria, 1%/1mm and 2%/2mm gamma passing rate results of plans on sCTtailor were always higher than plans on sCTICRU and sCTHomogeneity when compared with original CT based plans (P = 0.005). The difference on point dose in high dose planning target volume for each case calculated on sCTtailor (-0.14% ± 1.44%) was smaller if compared to those calculated on sCTICRU (-8.77% ± 2.33%) and sCTHomogeneity (1.65% ± 2.57%). The DVH differences for plan based on sCTtailor were much smaller than sCTICRU and sCTHomogeneity.The sCT generated with bulk rED assignment approach guarantees an acceptable level of dose accuracy for NPC patients with 1.5 T MR-Linac, making this approach suitable to online adaptive MR-guided radiotherapy. The accuracy can be improved by using patient-specific rED values.

Oligometastases Treated With an Elective Simultaneous Integrated Boost Have Reduced Marginal Recurrence Rates

<h3>Purpose/Objective(s)</h3> Radiation is increasingly used to treat oligometastatic patients (OM). Following metastasis directed radiation therapy, progression in nearby nodal basins or bones is common. We previously reported clinical outcomes of OM treated with an elective simultaneous integrated boost (SIB) technique delivering higher doses to known metastases and reduced doses to adjacent bones/nodal basins. Here we compare outcomes of OM receiving radiation to metastases alone (MA) versus those treated via an SIB. We hypothesized that use of SIB would maintain treated metastasis control (TMC) while reducing MR. <h3>Materials/Methods</h3> OM patients with ≤5 active metastases treated with either SIB or MA at our IRB approved sites from 2013-2018 were analyzed for toxicities, pain control, and recurrence patterns. TMC was defined as absence of progression in high dose planning target volume (PTV). Marginal recurrence (MR) was defined as recurrence outside elective PTV, but within the adjacent bone or nodal chain. Distant recurrence (DR) was defined as any recurrence outside of the treatment PTVs not meeting other criteria. Outcome rates were estimated using the Kaplan-Meier method. Patients treated with the two techniques were compared using the log rank test. <h3>Results</h3> 101 patients were treated to 90 SIB (58% nodal and 42% osseous) and 46 MA (22% nodal and 78% osseous) sites. The most common primary tumors were prostate (37%), lung (15%), and breast (7%). Median follow up among surviving patients was 24.6 months (range 1.4-71.0). Of the MA treated patients, doses ranged from 18 Gy in 1 fraction (22%) to 50 Gy in 10 fractions (50%). Most patients treated with SIB received 50 Gy to the treated metastases and 30 Gy to the elective PTV in 10 fractions (88%). No patients in either cohort experienced acute grade ≥3 toxicity. Late grade ≥3 toxicity occurred in 3 SIB patients (vocal cord paralysis n = 1, vertebral body compression n = 2) and no MA patients. There was similar crude pain relief between cohorts: 82% with MA (9/11 patients reporting improved pain) and 86% with SIB (19/22). Crude MR were more frequent in the MA group 13% (n = 6) compared to SIB group 2% (n = 2). MR-free survival at 2 years was 87% (95% CI: 70%, 95%) in the MA group and 98% (95% CI: 87%, 99%) in the SIB group (<i>P</i> = 0.07). Crude TMC was 89% (41/46) in the MA group and 94% (85/90) in the SIB group. There were no significant differences found in DR-free survival (<i>P</i> = 0.24) or Disease-free survival (<i>P</i> = 0.4) and Overall survival (<i>P</i> = 0.26) between MA and SIB cohorts. <h3>Conclusion</h3> Both SIB and MA irradiation of OM achieved high rates of TMC and similar pain control, with a trend towards improved MR-free survival for OM treated with SIB. Although more late grade 3 toxicities were seen in the SIB cohort, these were mechanistically related to the high dose PTV and not the elective volume, with differences in treated metastasis location/characteristics. Further investigation of this technique with prospective trials is warranted.

Can Radiation Therapy Quality Assurance Improve Nasopharyngeal Cancer Outcomes in Low- and Middle-Income Countries: Reporting the First Phase of a Prospective International Atomic Energy Agency Study

PurposeMost new nasopharyngeal cancer cases occur in low-income and middle-income countries, and these patients experience poorer overall survival than that of new nasopharyngeal cancer cases in high-income countries. The goal of this research project is to determine whether the introduction of a radiation therapy quality assurance program can ultimately improve outcomes for nasopharyngeal cancer patients in lower-income and middle-income countries. This study reports the results of the first phase of the International Atomic Energy Agency Coordinated Research Project (325-E3-TM-47712). Methods and MaterialsThis prospective study has 2 phases. Phase 1 is a survey of radiation therapy resources, patient characteristics and treatment, and results of radiation therapy quality assurance performed by the expert panel. An educational workshop reviewing phase 1 results for each center was completed before accrual of patients for phase 2. The ultimate aim of the study is to compare the first and second cohort of patients to see if quality assurance can result in fewer major protocol deviations and a 15% improvement in patients’ 3-year progression-free survival. ResultsOf 14 participating centers, 13 (93%) had computed tomography simulators and linear accelerators (LINAC) with intensity modulated radiation therapy (IMRT) capacity, median 3 LINAC (range, 1-13), and median 10 radiation oncologists (range, 5-51). The annual number of nasopharyngeal cancer cases irradiated was median 54 (range, 10-627). Five of 14 centers (36%) had no local radiation therapy quality assurance. For the current phase 1 study, 134 patients were evaluated, 82.1% had MRI staging, 99.3% had metastatic workup, 65.6% undifferentiated histology, 51% stage 3 and 49% stage 4. Radiation therapy quality assurance revealed 81 (60.4%) of 134 patients had major protocol violations in gross tumor volume and high dose planning target volume contours and/or dosimetry, 28.4% patients had borderline plans, 15 (11.2%) acceptable, and only 6 (4.2%) had inevitable compromise due to tumor extent. ConclusionsThis is the first International Atomic Energy Agency study to address the fundamental issue of treatment quality rather than altered treatment regimens. The high rate of unacceptable radiation therapy plans is a major concern, and we hope phase 2 will show a significant reduction and improved patient outcomes.

Conformal Avoidance of Normal Organs at Risk by Perfusion-Modulated Dose Sculpting in Tumor Single-Dose Radiation Therapy

Although 24 Gy single-dose radiation therapy (SDRT) renders >90% 5-year local relapse-free survival in human solid tumor lesions, SDRT delivery is not feasible in ∼50% of oligometastatic lesions owing to interference by dose/volume constraints of a serial organ at risk (OAR). Conformal OAR avoidance is based on a hypothetical model positing that the recently described SDRT biology specifically permits volumetric subdivision of the SDRT dose, such that high-intensity vascular drivers of SDRT lethality, generated within a major tumor subvolume exposed to a high 24 Gy dose (high-dose planning target volume [PTVHD]), would equilibrate SDRT signaling intensity throughout the tumor interstitial space, rendering bystander radiosensitization of a minor subvolume (perfusion-modulated dose sculpting PTV [PTVPMDS]), dose-sculpted to meet a serial OAR dose/volume constraint. An engineered PTVPMDS may thus yield tumor ablation despite PMDS dose reduction and conformally avoiding OAR exposure to a toxic dose. Dose fall-off within the PTVPMDS penumbra of oligometastatic lesions was planned and delivered by intensity modulated inverse dose painting. SDRT- and SDRT-PMDS-treated lesions were followed with periodic positron emission tomography/computed tomography imaging to assess local tumor control. Cumulative baseline 5-year local relapse rates of oligometastases treated with 24 Gy SDRT alone (8% relapses, n = 292) were similar in moderate PTVPMDS dose-sculpted (23-18 Gy, n = 76, 11% relapses, P = .36) and extreme dose-sculpted (<18 Gy, n = 61, 14% relapses, P = .29) lesions, provided the major 24 Gy PTVHD constituted ≥60% of the total PTV. In contrast, 28% of local relapses occurred in 26 extreme dose-sculpted PTVPMDS lesions when PTVHD constituted <60% of the total PTV (P = .004), suggesting a threshold for the PTVPMDS bystander effect. The study provides compelling clinical support for the bystander radiosensitization hypothesis, rendering local cure of tumor lesions despite a ≥25% PTVPMDS dose reduction of the 24 Gy PTVHD dose, adapted to conformally meet OAR dose/volume constraints. The SDRT-PMDS approach thus provides a therapeutic resolution to otherwise radioablation-intractable oligometastatic disease.

Conventionally fractionated large volume head and neck re-irradiation using multileaf collimator-based robotic technique: A feasibility study

PurposeTo report on the feasibility and performance of conventionally fractionated multileaf collimator (MLC)-based robotic stereotactic body re-irradiation of the head and neck region using MLC-based Cyberknife (CK) technology. MethodsPatients treated for recurrent or second primary head and neck cancer (HNC) with curative proton therapy to a target volume > 30 cm3 between 2011 and 2015 were included. MLC-based CK plans were generated using the CK M6 InCise2 MLC system. Dose statistics from MLC-based CK plans were compared to proton beam therapy (PBT) plans according to the following metrics: target coverage, target homogeneity index, gradient index, Paddick conformity index (CI), prescription isodose volume (PIV), treatment time (tTime) for one fraction as well as doses to organs at risk (OAR). Wilcoxon signed-rank test was used to compare dose metrics. ResultsEight patients were included; the tumor sites included: salivary glands, pharynx (oropharynx, hypopharynx and retropharynx) and sinonasal cavities. Five of 8 patients were treated with multifield optimisation intensity modulated proton therapy, 3 were treated with passive scattering proton therapy. Median dose was 67 Gy (range 60–70) in 32 fractions (range 30–35). The median high-dose planning target volume (PTV) was 45.4 cm3 (range 2.4 – 130.2 cm3) and the median elective PTV was 91.9 cm3 (range 61.2 – 269.7 cm3). Overall, the mean target coverage (mean 98.3% vs. 96.2% for CK vs. PBT, respectively), maximum dose to PTV (mean 111% vs. 111%, p = 0.2) and mean dose to PTV (mean 104% vs. 104%) were similar across modalities. Highly conformal plans were achieved with both modalities, but mean CI was better with PBT (0.5 vs. 0.6 for CK vs. PBT, p = 0.04). Homogeneity and gradient indexes were similar between the 2 modalities; mean tTime with PBT and CK was 17 vs. 18 min, respectively (p = 0.7). Case-based study revealed that CK and PBT plans allowed for excellent sparing of OAR, with some clinical scenarios associated with better performance of CK while others with better performance of PBT. ConclusionOur study has demonstrated the dosimetric performance of large volume head and neck re-irradiation using MLC-based CK in various clinical scenarios. While conformity was generally better achieved with PBT, MLC-based CK allowed for high dose gradient leading to rapid dose drop-off and sparing of OAR. Conventionally fractionated MLC-based CK could be a competitive alternative in large volume head and neck re-irradiation that deserves further investigation in the clinical setting.

Abstract B30: Locoregional control in laryngeal and hypopharyngeal cancer patients treated with radiotherapy using direct gross tumor volume to planning target volume expansion

Abstract Purposes/Objectives(s): To evaluate clinical outcomes and patterns of failure using a direct gross tumor volume to planning target volume expansion in patients treated for laryngeal or hypopharyngeal squamous cell carcinomas. Methods and Materials: We performed a retrospective review of patients with laryngeal or hypopharyngeal squamous cell carcinomas treated between 2002-2017 with primary radiotherapy with or without concurrent systemic therapy. Patient and disease characteristics associated with disease control and clinical outcomes were analyzed by Cox proportional hazards regression and Kaplan-Meier analyses. Deformable image registration between imaging at the time of failure and the treatment planning scan was used to determine patterns of failure. Results: Seventy-nine patients with laryngeal or hypopharyngeal squamous cell carcinoma were identified with a median follow-up of 54 months among surviving patients. Overall survival at 5 years was 62.9% (95% CI: 51.1%-74.7%). Five-year primary tumor control was 71.6% (95% CI: 61.4%-81.8%) and regional control was 78.8% (95% CI: 68.4%-89.2%). A total of 28 patients experienced a locoregional recurrence, of whom 18 had treatment plans available. Of these, 89% (n=16) experienced failures that were 95% contained within the high-dose treatment volume. One patient failed in an intermediate-dose volume and 1 exhibited a marginal failure in the high-dose volume. There were no factors associated with overall survival or locoregional control on multivariate analysis. Conclusion: Management of patients with laryngeal or hypopharyngeal squamous cell carcinoma using definitive radiotherapy and a high-dose planning target volume created without a gross tumor volume to clinical tumor volume expansion resulted in high locoregional control, with the vast majority of failures occurring within the high-dose field. These data support prospective evaluation of this technique. Citation Format: Adam R. Burr, Paul M. Harari, Matthew E. Witek. Locoregional control in laryngeal and hypopharyngeal cancer patients treated with radiotherapy using direct gross tumor volume to planning target volume expansion [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr B30.

Dose to medium in head and neck radiotherapy: Clinical implications for target volume metrics.

Background and purposeIn radiotherapy dose calculation, advanced type-B dose calculation algorithms can calculate dose to medium (Dm), as opposed to Type-B algorithms which compute dose to varying densities of water (Dw). We investigate the impact of Dm on calculated dose and target coverage metrics in head and neck cancer patients.Methods and materialsWe reviewed 27 successfully treated (disease free at two-years post-(chemo)radiotherapy) human papillomavirus-associated (HPV) oropharyngeal cancer (ONC) patients treated with IMRT. Doses were calculated with Type-B and Linear Boltzman Transport Equation (LBTE) algorithms in a commercial treatment planning system, with the treated multi-leaf collimator patterns and monitor units. Coverage for primary Gross Tumour Volume (GTVp), high dose Planning Target Volume (PTV) (PTV_High), mandible within PTV_High (Mand ∩ PTV) and PTV_High excluding bone (PTV-bone) were compared between the algorithms.ResultsDose to 95% of PTV_High with LBTE was on average 1.1 Gy/1.7% lower than with Type-B (95%CI 1.5–1.9%, p < 0.0001). This magnitude was inversely linearly correlated with the relative volume of the PTV_High containing bone (pearson r = −0.81). Dose to 98% of the GTVp was 0.9 Gy/1.3% lower with LBTE compared with Type-B (95%CI 1.1–1.5%, p < 0.05). Dose to 98% of Mand ∩ PTV was on average 3.4 Gy/5.0% lower with LBTE than with Type-B (95%CI 4.6–5.4%, p < 0.0001).ConclusionIn OPC treated with IMRT, Dm results in significant reductions in dose to bone in high dose PTVs. Reported GTVp dose was reduced, but by a lower magnitude. Reduced coverage metrics should be expected for OPC patients treated with IMRT, with dose reductions limited to regions of bone.

Evaluation of auto-planning in IMRT and VMAT for head and neck cancer.

PurposeThe purposes of this work are to (a) investigate whether the use of auto‐planning and multiple iterations improves quality of head and neck (HN) radiotherapy plans; (b) determine whether delivery methods such as step‐and‐shoot (SS) and volumetric modulated arc therapy (VMAT) impact plan quality; (c) report on the observations of plan quality predictions of a commercial feasibility tool.Materials and methodsTwenty HN cases were retrospectively selected from our clinical database for this study. The first ten plans were used to test setting up planning goals and other optimization parameters in the auto‐planning module. Subsequently, the other ten plans were replanned with auto‐planning using step‐and‐shoot (AP‐SS) and VMAT (AP‐VMAT) delivery methods. Dosimetric endpoints were compared between the clinical plans and the corresponding AP‐SS and AP‐VMAT plans. Finally, predicted dosimetric endpoints from a commercial program were assessed.ResultsAll AP‐SS and AP‐VMAT plans met the clinical dose constraints. With auto‐planning, the dose coverage of the low dose planning target volume (PTV) was improved while the dose coverage of the high dose PTV was maintained. Compared to the clinical plans, the doses to critical organs, such as the brainstem, parotid, larynx, esophagus, and oral cavity were significantly reduced in the AP‐VMAT (P < 0.05); the AP‐SS plans had similar homogeneity indices (HI) and conformality indices (CI) and the AP‐VMAT plans had comparable HI and improved CI. Good agreement in dosimetric endpoints between predictions and AP‐VMAT plans were observed in five of seven critical organs.ConclusionWith improved planning quality and efficiency, auto‐planning module is an effective tool to enable planners to generate HN IMRT plans that are meeting institution specific planning protocols. DVH prediction is feasible in improving workflow and plan quality.

Rapid in-field failures following adjuvant radiation for buccal squamous cell carcinoma.

Squamous cell carcinoma originating in the buccal mucosa and retromolar trigone (RMT) have historically poor outcomes. Difficulties in discriminating tumor origin often result in these subsites being combined in surgical and pathological reports. We aimed to determine if making this anatomical distinction has implications for treatment design and clinical outcomes. Retrospective case series. We identified 27 tumors from either the buccal mucosa patients or RMT patients who underwent surgery followed by radiation. For patients who developed a local failure, we fused the pretreatment imaging, simulation computed tomography, and follow-up imaging to determine the location of failures relative to the radiation field. We calculated the 2-year locoregional control and 2-year disease-free survival. The median time from surgery to radiation was 50 days (range, 32-133 days). The 2-year locoregional control for buccal mucosa versus RMT, respectively, were 35.9% versus 68.4% (P = .252). The 2-year disease-free survival rates were 32.7% versus 68.4%, respectively (P = .196). The median times to failure were 12.00 months (range, 4.9-115.0 months) versus 18.5 months (range, 4.5-61.0 months), respectively. All buccal mucosa failures occurred within the high-dose planning target volume, with a median dose of 60 Gy within the failure region. Following locoregional failure, 10 of the 12 patients have died, with a median time from local failure to death of 3.6 months (range, 1-17.6 months). Squamous cell carcinomas of the buccal mucosa appear to have a poor prognosis characterized by rapid in-field failure. Therefore, differentiating tumor origin may be important for prognostication and treatment. 3 Laryngoscope, 130:413-417, 2020.

Correlations between the shifts in prompt gamma emission profiles and the changes in daily target coverage during simulated pencil beam scanning proton therapy

The aim of this study was to investigate the feasibility of using prompt gamma (PG) ray emission profiles to monitor changes in dose to the planning target volume (PTV) during pencil beam scanning (PBS) proton therapy as a result of day-to-day variation in patient anatomy.For 11 prostate patients, we simulated treatment plan delivery using the patients’ daily anatomy as observed in the planning CT and 7–9 control CT scans, including the detected PG profiles resulting from the 5%, 10%, and 20% most intense proton pencil beams. For each patient, we determined the changes in dosimetric parameters for the high- and low-dose PTVs between the simulations performed using the planning CT scan and the different control CT scans and correlated these to changes in the PG emission profiles.Changes in coverage of the high- and low-dose PTV correlated most strongly with the median and mean absolute PG emission profile shifts of the 5% most intense pencil beams, respectively. With a mean Pearson correlation coefficient of −0.76 (SD: 0.17) for the high-dose PTV and of −0.60 (SD: 0.51) for the low-dose PTV.We showed, as a proof of principle, that PG emission profiles obtained during PBS proton therapy could be used to detect changes in PTV coverage due to day-to-day anatomical variation.

Reducing radiotherapy target volume expansion for patients with HPV-associated oropharyngeal cancer

PurposeTo evaluate clinical outcomes and patterns of failure using a direct gross tumor volume to planning target volume expansion in patients with p16-positive oropharyngeal squamous cell carcinoma. Methods and materialsWe performed a retrospective review of patients with p16-positive oropharyngeal squamous cell carcinomas treated between 2002 and 2017 with primary radiotherapy with or without concurrent systemic therapy. Patient and disease characteristics associated with disease control and clinical outcomes were analyzed by Cox proportional hazards regression and Kaplan-Meier analyses. Imaging at the time of first failure was used to categorize failure patterns. ResultsWe identified 134 patients with a median follow-up of 56.2 months (range 8.2–160.2 months). Local and regional control at 5 years was 91.5% (95% CI: 86.8–96.4%), and 90.8% (95% CI: 85.6–96.2%), respectively. Of the 14 locoregional failures, there were 10 in-field (Type A), 3 marginal (Type B), and 1 geographic (Type E). Age >70 years (HR 5.42; 95% CI: 1.87–15.68) and T4 versus T1-3 (HR 4.09; 95% CI: 1.01–2.65) were associated with increased rates of locoregional failure on multivariate analysis. The rate of gastrostomy tube retention at one year was 6.0% (range 2.8–12.7%). ConclusionsManagement of patients with p16-positive oropharyngeal squamous cell carcinoma using definitive radiotherapy and a high-dose planning target volume created without a gross tumor volume to clinical tumor volume expansion resulted in high locoregional control with the vast majority of failures occurring within the high-dose field. These data warrant prospective evaluation of this technique as a therapy de-intensification approach.

The Association of Canonical Speech- and Swallow-Related Dosimetric Constraints with Patient-Reported Quality of Life Outcomes: Results from a Phase II Trial of Dose De-Escalated Chemoradiation for HPV-Associated, Locally-Advanced Oropharyngeal Carcinoma

Radiation dose de-escalation for patients with human papillomavirus (HPV)-related oropharyngeal carcinoma may improve quality of life. We conducted an exploratory exercise to examine potential relationships between canonical dosimetric parameters and speech- and swallow-related and overall patient-reported quality of life outcomes on a subset of patients treated on a phase II trial of de-escalated chemoradiation for HPV-related oropharyngeal carcinoma. An analysis was performed of 24 patients treated at a single-institution on a phase II, prospective study of induction chemotherapy followed by dose de-escalated chemoradiation for HPV-related, locally-advanced oropharyngeal carcinoma. Following two cycles of induction carboplatin/paclitaxel, reduced-dose chemoradiation with concurrent paclitaxel was administered to 54-60 Gy in 27-30 fractions. Intensity-modulated radiotherapy was used for all patients. Univariable logistic regression analysis was used to evaluate potential associations between multiple speech-and swallow-related dosimetric constraints and quality of life domains at 3 and 12 months post-treatment involving swallowing, chewing, speech, taste, and saliva, as well as overall quality of life, using the University of Washington Quality of Life instrument. Canonical models were constructed to analyze dosimetry to the temporomandibular joints, oral cavity, lips, parotid glands, submandibular glands, larynx, pharynx, cricopharyngeal inlet, and cervical esophagus, as analyzed by maximum, mean, and/or partial-volume parameters. The post-chemotherapy gross tumor volume, planning target volume (PTV) receiving the high, intermediate, and low dose levels, and combined volume of all PTV dose levels were also analyzed. Twenty-five percent of patients had T3-T4 tumors, and 13% had N2c nodal disease. Thirteen percent had >10 pack-year smoking history. At 12 months, a decreased taste domain score was significantly associated with a higher volume of high-dose level PTV (p=0.028). Also, a decreased health-related quality of life score at 12 months was significantly associated with a higher contralateral parotid gland mean dose (p=0.037), higher contralateral parotid gland V30Gy (p=0.046), and higher cricopharyngeal inlet mean dose (p=0.036). No dosimetric parameters were significantly associated with quality of life differences at 3 months (p>0.05, for all). For patients treated by de-escalated chemoradiation, canonical dosimetric constraints for conventional chemoradiation are poorly correlated with speech- and swallow-related and overall quality of life outcomes. While a smaller high-dose PTV, lower contralateral parotid gland dose, and lower cricopharyngeal inlet dose appear to be related to better quality of life outcomes, these require additional validation. Future studies of de-escalated chemoradiation may reveal new dosimetric constraints to help guide treatment planning.

Magnetic Resonance-based Response Assessment and Dose Adaptation in Human Papilloma Virus Positive Tumors of the Oropharynx treated with Radiotherapy (MR-ADAPTOR): An R-IDEAL stage 2a-2b/Bayesian phase II trial

BackgroundCurrent standard radiotherapy for oropharynx cancer (OPC) is associated with high rates of severe toxicities, shown to adversely impact patients’ quality of life. Given excellent outcomes of human papilloma virus (HPV)-associated OPC and long-term survival of these typically young patients, treatment de-intensification aimed at improving survivorship while maintaining excellent disease control is now a central concern. The recent implementation of magnetic resonance image – guided radiotherapy (MRgRT) systems allows for individual tumor response assessment during treatment and offers possibility of personalized dose-reduction. In this 2-stage Bayesian phase II study, we propose to examine weekly radiotherapy dose-adaptation based on magnetic resonance imaging (MRI) evaluated tumor response. Individual patient’s plan will be designed to optimize dose reduction to organs at risk and minimize locoregional failure probability based on serial MRI during RT. Our primary aim is to assess the non-inferiority of MRgRT dose adaptation for patients with low risk HPV-associated OPC compared to historical control, as measured by Bayesian posterior probability of locoregional control (LRC). MethodsPatients with T1-2 N0-2b (as per AJCC 7th Edition) HPV-positive OPC, with lymph node <3 cm and <10 pack-year smoking history planned for curative radiotherapy alone to a dose of 70 Gy in 33 fractions will be eligible. All patients will undergo pre-treatment MRI and at least weekly intra-treatment MRI. Patients undergoing MRgRT will have weekly adaptation of high dose planning target volume based on gross tumor volume response. The stage 1 of this study will enroll 15 patients to MRgRT dose adaptation. If LRC at 6 months with MRgRT dose adaptation is found sufficiently safe as per the Bayesian model, stage 2 of the protocol will expand enrollment to an additional 60 patients, randomized to either MRgRT or standard IMRT. DiscussionMultiple methods for safe treatment de-escalation in patients with HPV-positive OPC are currently being studied. By leveraging the ability of advanced MRI techniques to visualize tumor and soft tissues through the course of treatment, this protocol proposes a workflow for safe personalized radiation dose-reduction in good responders with radiosensitive tumors, while ensuring tumoricidal dose to more radioresistant tumors. MRgRT dose adaptation could translate in reduced long term radiation toxicities and improved survivorship while maintaining excellent LRC outcomes in favorable OPC. Trial registrationClinicalTrials.gov ID: NCT03224000; Registration date: 07/21/2017.