Dose Painting Research Articles

Protocol compliance in a multicentric phase III trial investigating scheduled adaptive radiotherapy and dose painting in head and neck cancer

PurposeTo report on quality assurance (QA) and protocol adherence (PA) in a multicentre phase III trial for head and neck cancer, evaluate patterns of protocol deviations and investigate the effect of PA on study outcomes. MethodsAll 221 patients from the ARTFORCE trial (NCT01504815) were included in this study. Pre- and per-treatment QA measures included protocol guidelines, a dummy run, early case reviews and trial meetings. FDG-PET-guided dose painting and scheduled adaptive radiotherapy were reviewed in patients in the experimental arm (eRT). Patient and disease characteristics, as well as institutes’ accrual rate and timing were examined for correlation with PA. Cox regression was used to determine the impact of PA on outcome. ResultsThe dummy run was completed in all nine institutes and early case reviews were completed in five out of nine institutes that contributed 190 out of 221 patients. Among all patients randomized to eRT, 64 % had at least one deviation of the experimental trial components. Protocol deviations were significantly correlated with the institute patients were treated at (Cramer’sV 0.34–0.48). Despite early identification of institute-specific deviations in QA, these continued during the trial. No significant associations were seen between deviations and accrual timing or rate (P ≥ 0.26). Within eRT, no significant relation was observed between experimental PA and locoregional control (LRC), the primary endpoint of the trial (P≥.15). ConclusionsDespite QA, protocol deviations persisted during the trial, which were mostly institute-specific. However, deviations of the experimental treatment strategy did not significantly impact LRC and therefore the trial conclusion.

Tumor Hypoxia and Radioresistance

Tumor hypoxia is a prevalent feature of solid tumors, significantly contributing to increased tumor aggressiveness, metastatic potential, and resistance to conventional therapies such as radiotherapy. This review explores the complex relationship between tumor hypoxia and radioresistance, highlighting the molecular mechanisms involved and potential therapeutic strategies to enhance radiotherapy efficacy in hypoxic tumors. Key mechanisms include the role of hypoxia-inducible factors (HIFs), particularly HIF-1α, which regulates numerous genes involved in tumor survival, proliferation, and resistance under hypoxic conditions. The review also discusses the oxygen enhancement ratio (OER) and its impact on radiotherapy outcomes, emphasizing how hypoxia leads to reduced radiosensitivity by limiting the formation of radiation-induced DNA damage. Despite the development of various strategies to counteract hypoxia-induced radioresistance, such as HIF inhibitors, hypoxia-targeted gene therapy, and hypoxia-activated prodrugs (HAPs), clinical results have been mixed, necessitating further research. Additionally, advances in imaging techniques for detecting tumor hypoxia are explored, which may allow for more personalized radiotherapy approaches, such as dose painting. The future of overcoming tumor hypoxia in radiotherapy lies in the integration of innovative therapeutic strategies, personalized medicine, and improved imaging technologies, offering hope for enhanced treatment outcomes in cancer patients.

Impact of geometric correction on echo-planar imaging-based apparent diffusion coefficient maps for abdominal radiotherapy

Objective. The apparent diffusion coefficient (ADC) extracted from diffusion-weighted magnetic resonance imaging (DWI) is a potential biomarker in radiotherapy (RT). DWI is often implemented with an echo-planar imaging (EPI) read-out due to speed, but unfortunately low geometric accuracy follows. This study aimed to investigate the influence of geometric distortions on the ADCs extracted from the gross tumor volume (GTV) and on the shape of the GTV in abdominal EPI-DWI. Approach. Twenty-one patients had EPI-DWI scans on a 1.5 T MRI sim before treatment and on a 1.5 T MRI-Linac at one of the first treatment fractions. Off-resonance correction with and without eddy current correction were applied to ADC maps. The clinical GTVs were deformed based on the same (but inverted) corrections to assess the local-regional geometric influence of distortions. Mean surface distance (MSD), Hausdorff distance (HD), and Dice similarity coefficient (DSC) were calculated to compare the original and distorted GTVs, and ADC values were calculated based on a mono-exponential model. Phantom measurements were performed to validate the applied correction method. Main results. The median (range) ADC change within the GTV after full distortion correction was 1.3% (0.02%–6.9%) for MRI-Sim and 1.5% (0.1%–6.4%) for MRI-Linac. The additional effect of the eddy current correction was small in both systems. The median (range) MSD, HD, and DSC comparing the original and off-resonance distorted GTVs for all patients were 0.43 mm (0.11–0.94 mm), 4.00 mm (1.00–7.81 mm) and 0.93 (0.82–0.99), respectively. Significance. Overall effect of distortion correction was small in terms of derived ADC values, indicating that distortion correction is unimportant for prediction of outcomes based on ADC. However, large local geometric changes occurred after off-resonance distortion correction for some patients, suggesting that if the spatial information from ADC maps is to be used for dose painting strategies, corrections should be applied.

1771: Evaluating image-guided dose painting for skull-based chordoma patients treated with proton therapy

1771: Evaluating image-guided dose painting for skull-based chordoma patients treated with proton therapy

Optimization and validation of low-field MP2RAGE T1 mapping on 0.35T MR-Linac: Toward adaptive dose painting with hypoxia biomarkers.

Stereotactic MR-guided Adaptive Radiation Therapy (SMART) dose painting for hypoxia has potential to improve treatment outcomes, but clinical implementation on low-field MR-Linac faces substantial challenges due to dramatically lower signal-to-noise ratio (SNR) characteristics. While quantitative MRI and T1 mapping of hypoxia biomarkers show promise, T1-to-noise ratio (T1NR) optimization at low fields is paramount, particularly for the clinical implementation of oxygen-enhanced (OE)-MRI. The 3D Magnetization Prepared (2) Rapid Gradient Echo (MP2RAGE) sequence stands out for its ability to acquire homogeneous T1-weighted contrast images with simultaneous T1 mapping. To optimize MP2RAGE for low-field T1 mapping; conduct experimental validation in a ground-truth phantom; establish feasibility and reproducibility of low-field MP2RAGE acquisition and T1 mapping in healthy volunteers. The MP2RAGE optimization was performed to maximize the contrast-to-noise ratio (CNR) of T1 values in white matter (WM) and gray matter (GM) brain tissues at 0.35T. Low-field MP2RAGE images were acquired on a 0.35T MR-Linac (ViewRay MRIdian) using a multi-channel head coil. Validation of T1 mapping was performed with a ground-truth Eurospin phantom, containing inserts of known T1 values (400-850ms), with one and two average (1A and 2A) MP2RAGE scans across four acquisition sessions, resulting in eight T1 maps. Mean (±SD) T1 relative error, T1NR, and intersession coefficient of variation (CV) were determined. Whole-brain MP2RAGE scans were acquired in 5 healthy volunteers across two sessions (A and B) and T1 maps were generated. Mean (±SD) T1 values for WM and GM were determined. Whole-brain T1 histogram analysis was performed, and reproducibility was determined with the CV between sessions. Voxel-by-voxel T1 difference maps were generated to evaluate 3D spatial variation. Low-field MP2RAGE optimization resulted in parameters: MP2RAGETR of 3250ms, inversion times (TI1/TI2) of 500/1200ms, and flip angles (α1/α2) of 7/5°. Eurospin T1 maps exhibited a mean (±SD) relative error of 3.45%±1.30%, T1NR of 20.13±5.31, and CV of 2.22%±0.67% across all inserts. Whole-brain MP2RAGE images showed high anatomical quality with clear tissue differentiation, resulting in mean (±SD) T1 values: 435.36±10.01ms for WM and 623.29±14.64ms for GM across subjects, showing excellent concordance with literature. Whole-brain T1 histograms showed high intrapatient and intersession reproducibility with characteristic intensity peaks consistent with voxel-level WM and GM T1 values. Reproducibility analysis revealed a CV of 0.46%±0.31% and 0.35%±0.18% for WM and GM, respectively. Voxel-by-voxel T1 difference maps show a normal 3D spatial distribution of noise in WM and GM. Low-field MP2RAGE proved effective in generating accurate, reliable, and reproducible T1 maps with high T1NR in phantom studies and in vivo feasibility established in healthy volunteers. While current work is focused on refining the MP2RAGE protocol to enable clinically efficient OE-MRI, this study establishes a foundation for TOLD T1 mapping for hypoxia biomarkers. This advancement holds the potential to facilitate a paradigm shift toward MR-guided biological adaptation and dose painting by leveraging 3D hypoxic spatial distributions and improving outcomes in conventionally challenging-to-treat cancers.

Non-small cell lung cancer and metabolism research from 2013 to 2023: a visual analysis and bibliometric study.

As one of the most prevalent primary lung tumors, non-small cell lung cancer (NSCLC) has garnered considerable research interest due to its high metastasis rates and poor prognosis outcomes. Across different cancer types, metabolic processes are required for tumors progression and growth, thus interfering with such processes in NSCLC may therapeutically viable for limiting/halting disease progression. Therefore, comprehending how metabolic processes contribute to growth and survival mechanisms in cancers, including NSCLC, may elucidate key functions underpinning tumor cell metabolism. However, no bibliometric analyses have been published in this field, therefore we address this knowledge gap here. Between 2013 and 2023 (December 28th), articles related to the NSCLC and metabolism (NSCLC-Met) field were retrieved from the Web of Science Core Collection (WoSCC). To fully dissect NSCLC-Met research directions and articles, we used the Bibliometrix package in R, VOSviewer and CiteSpace software to visually represent global trends and hotspots. Between 2013 and 2023, 2,246 NSCLC-Met articles were retrieved, with a continuous upward trend and rapid development observed year on year. Cancers published the most articles, with Cancer Research recording the highest average citation numbers. Zhang Li from China was the most prolific author, but the highest number of authors came from the USA. China, USA, and Italy were the top three countries with the highest number of published articles, with close cooperation identified between countries. Recent hotspots and research directions were reflected by "lung adenocarcinoma", "immunotherapy", "nivolumab", "checkpoint inhibitors", "blockade", and "pembrolizumab", while "gut microbiome", "egfr" and "dose painting" were important topics for researchers. From our analyses, scientists can now explore new hotspots and research directions in the NSCLC-Met field. Further in-depth research in this field will undoubtedly provide more new insights on disease diagnostics, treatment, and prognostics.

Treatment Planning Methods for Dose Painting by Numbers Treatment in Gamma Knife Radiosurgery

PURPOSEDose painting radiotherapy delivers a non-uniform dose to tumours to account for heterogeneous radiosensitivity. With recent and ongoing development of Gamma Knife (GK) machines making large-volume brain tumour treatments more practical, it is increasingly feasible to deliver dose painting treatments. The increased prescription complexity means automated treatment planning is greatly beneficial, and the impact of dose painting on SRS plan quality has not yet been studied. This research investigates the plan quality achievable for GK SRS dose painting treatments when using optimisation techniques and automated isocentre placement in treatment planning. METHODS & MATERIALSDose painting prescription functions with varying parameters are applied to convert voxel image intensities to prescriptions for ten sample cases. To study achievable plan quality and optimisation, clinically-placed isocentres are used with each dose painting prescription, and optimised using a semi-infinite linear programming formulation. To study automated isocentre placement, a grassfire sphere-packing algorithm and a clinically available Leksell Gamma Plan isocentre fill algorithm are used. Plan quality for each optimised treatment plan is measured with dose painting SRS metrics. RESULTSOptimisation can be used to find high quality dose painting plans, and plan quality is affected by the dose painting prescription method. Polynomial function prescriptions show better achievable plan quality than sigmoid function prescriptions even with high mean dose boost. Automated isocentre placement is shown as a feasible method for dose painting SRS treatment, and increasing the number of isocentres improves plan quality. The computational solve time for optimisation is within 5 minutes in most cases, which is suitable for clinical planning. CONCLUSIONSThe impact of dose painting prescription method on achievable plan quality is quantified in this study. Optimisation and automated isocentre placement are shown as possible treatment planning methods to obtain high quality plans.

Interventional radiotherapy (brachytherapy) for re-irradiation of recurrent head and neck malignancies: oncologic outcomes and morbidity.

Management of recurrent head and neck cancer (HNC) is challenging. One option in previously irradiated patients is re-irradiation using interventional radiotherapy (IRT), the modern form of brachytherapy. Re-irradiation using IRT can be delivered as an exclusive strategy for salvage or through a postoperative or perioperative approach after salvage surgery. The aim of the present study is to analyse a bicentric Italian series focusing on the use of IRT as a re-irradiation modality and assess the resulting evidence concerning oncologic outcomes and morbidity. This is a retrospective study performed in two referral centres in Italy: Policlinico Universitario Agostino Gemelli in Rome and Azienda Ospedaliera Universitaria in Sassari. All patients who had previously received a full course of external beam RT and have been re-irradiated using high-dose-rate IRT between December 2010 and June 2023 were included. Patients were retreated either by a combination of surgery and perioperative (either endocavitary or interstitial) IRT or by exclusive interstitial IRT. Thirty-four patients were included in the present series, 2 of whom underwent more than one IRT re-irradiation. Notably, no patient reported specific IRT-related toxicities. Median follow-up, excluding patients who died of HNC, was 24.5 months. Two-year local relapse-free survival was 26%, disease-specific survival 39.1%, and overall survival 36.6%. The present series is the largest reported experience of re-irradiation by IRT for HNC in Italy. The very low rate of toxicity confirms IRT as the safest re-irradiation modality. It is noteworthy to underline that IRT is a multidisciplinary strategy based on the close cooperation between surgeons and radiation oncologists during every phase, from the recommendation of treatment and implantation in the operating theatre, to its prescription and dose painting.

483: Clinical outcomes after dose painting of head and neck cancer with poor prognosis

483: Clinical outcomes after dose painting of head and neck cancer with poor prognosis

Advancements and future directions in positron emission tomography-guided radiotherapy: a narrative review.

Positron emission tomography (PET) imaging has been useful in delineating tumor volumes and allowing for improved radiation treatment. The field of PET-guided radiotherapy is rapidly growing and will have significant impact on radiotherapy delivery in the future. This narrative review provides an overview of the current state of PET-guided radiotherapy as well as the future directions of the field. For this narrative review, PubMed was searched for articles from 2010-2023. A total of 18 keywords or phrases were searched to provide an overview of PET-guided radiotherapy, radiotracers, the role of PET-guided radiotherapy in oligometastatic disease, and biology-guided radiotherapy (BgRT). The first 300 results for each keyword were searched and relevant articles were extracted. The references of these articles were also reviewed for relevant articles. In radiotherapy, 18F-2-fluoro-2-deoxy-D-glucose (F-FDG or FDG) is the major radiotracer for PET and when combined with computed tomography (CT) scan allows for anatomic visualization of metabolically active malignancy. Novel radiotracers are being explored to delineate certain cell types and numerous tumor metrics including metabolism, hypoxia, vascularity, and cellular proliferation. This molecular and functional imaging will provide improved tumor characterization. Through these radiotracers, radiation plans can employ dose painting by creating different dose levels based upon specific risk factors of the target volume. Additionally, biologic imaging during radiotherapy can allow for adaptation of the radiation plan based on response to treatment. Dose painting and adaptive radiotherapy should improve the therapeutic ratio through more selective dose delivery. The novel PET-linear accelerator hopes to combine these techniques and more by using radiotracers to deliver BgRT. The areas of radiotracer uptake will serve as fiducials to guide radiotherapy to themselves. This technique may prove promising in the growing area of oligometastatic radiation treatment. Significant challenges exist for the future of PET-guided radiotherapy. However, with the advancements being made, PET imaging is set to change the delivery of radiotherapy.

PET/SPECT/Spectral-CT/CBCT imaging in a small-animal radiation therapy platform: A Monte Carlo study-Part II: Biologically guided radiotherapy.

This study addresses the technical gap between clinical radiation therapy (RT) and preclinical small-animal RT, hindering the comprehensive validation of innovative clinical RT approaches in small-animal models of cancer and the translation of preclinical RT studies into clinical practices. The main aim was to explore the feasibility of biologically guided RT implemented within a small-animal radiation therapy (SART) platform, with integrated quad-modal on-board positron emission tomography (PET), single-photon emission computed tomography, photon-counting spectral CT, and cone-beam CT (CBCT) imaging, in a Monte Carlo model as a proof-of-concept. We developed a SART workflow employing quad-modal imaging guidance, integrating multimodal image-guided RT and emission-guided RT (EGRT). The EGRT algorithm was outlined using positron signals from a PET radiotracer, enabling near real-time adjustments to radiation treatment beams for precise targeting in the presence of a 2-mm setup error. Molecular image-guided RT, incorporating a dose escalation/de-escalation scheme, was demonstrated using a simulated phantom with a dose painting plan. The plan involved delivering a low dose to the CBCT-delineated planning target volume (PTV) and a high dose boosted to the highly active biological target volume (hBTV) identified by the 18F-PET image. Additionally, the Bayesian eigentissue decomposition method illustrated the quantitative decomposition of radiotherapy-related parameters, specifically iodine uptake fraction and virtual noncontrast (VNC) electron density, using a simulated phantom with Kidney1 and Liver2 inserts mixed with an iodine contrast agent at electron fractions of 0.01-0.02. EGRT simulations generated over 4,000 beamlet responses in dose slice deliveries and illustrated superior dose coverage and distribution with significantly lower doses delivered to normal tissues, even with a 2-mm setup error introduced, demonstrating the robustness of the novel EGRT scheme compared to conventional image-guided RT. In the dose-painting plan, doubling the dose to the hBTV while maintaining a low dose for the PTV resulted in an organ-at-risk (OAR) dose comparable to the low-dose treatment for the PTV alone. Furthermore, the decomposition of radiotherapy-related parameters in Kidney1 and Liver2 inserts, including iodine uptake fractions and VNC electron densities, exhibited average relative errors of less than 1.0% and 2.5%, respectively. The results demonstrated the successful implementation of biologically guided RT within the proposed quad-model image-guided SART platform, with potential applications in preclinical RT and adaptive RT studies.

Rethinking the potential role of dose painting in personalized ultra-fractionated stereotactic adaptive radiotherapy.

Fractionated radiotherapy was established in the 1920s based upon two principles: (1) delivering daily treatments of equal quantity, unless the clinical situation requires adjustment, and (2) defining a specific treatment period to deliver a total dosage. Modern fractionated radiotherapy continues to adhere to these century-old principles, despite significant advancements in our understanding of radiobiology. At UT Southwestern, we are exploring a novel treatment approach called PULSAR (Personalized Ultra-Fractionated Stereotactic Adaptive Radiotherapy). This method involves administering tumoricidal doses in a pulse mode with extended intervals, typically spanning weeks or even a month. Extended intervals permit substantial recovery of normal tissues and afford the tumor and tumor microenvironment ample time to undergo significant changes, enabling more meaningful adaptation in response to the evolving characteristics of the tumor. The notion of dose painting in the realm of radiation therapy has long been a subject of contention. The debate primarily revolves around its clinical effectiveness and optimal methods of implementation. In this perspective, we discuss two facets concerning the potential integration of dose painting with PULSAR, along with several practical considerations. If successful, the combination of the two may not only provide another level of personal adaptation ("adaptive dose painting"), but also contribute to the establishment of a timely feedback loop throughout the treatment process. To substantiate our perspective, we conducted a fundamental modeling study focusing on PET-guided dose painting, incorporating tumor heterogeneity and tumor control probability (TCP).

Disease Control and Late Toxicity in Adaptive Dose Painting by Numbers Versus Nonadaptive Radiation Therapy for Head and Neck Cancer: A Randomized Controlled Phase 2 Trial

Local recurrence remains the main cause of death in stage III-IV nonmetastatic head and neck cancer (HNC), with relapse-prone regions within high 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET)-signal gross tumor volume. We investigated if dose escalation within this subvolume combined with a 3-phase treatment adaptation could increase local (LC) and regional (RC) control at equal or minimized radiation-induced toxicity, by comparing adaptive 18F-FDG-PET voxel intensity-based dose painting by numbers (A-DPBN) with nonadaptive standard intensity modulated radiation therapy (S-IMRT). This 2-center randomized controlled phase 2 trial assigned (1:1) patients to receive A-DPBN or S-IMRT (+/-chemotherapy). Eligibility: nonmetastatic HNC of oral cavity, oro-/hypopharynx, or larynx, needing radio(chemo)therapy; T1-4N0-3 (exception: T1-2N0 glottic); KPS ≥ 70; ≥18 years; and informed consent. 1-year LC and RC. The dose prescription for A-DPBN was intercurrently adapted in 2 steps to an absolute dose-volume limit (≤1.75 cm3 can receive >84 Gy and normalized isoeffective dose >96 Gy) as a safety measure during the study course after 4/7 A-DPBN patients developed ≥G3 mucosal ulcers. Ninety-five patients were randomized (A-DPBN, 47; S-IMRT, 48). Median follow-up was 31 months (IQR, 14-48 months); 29 patients died (17 of cancer progression). A-DPBN resulted in superior LC compared with S-IMRT, with 1- and 2-year LC of 91% and 88% versus 78% and 75%, respectively (hazard ratio, 3.13; 95% CI, 1.13-8.71; P = .021). RC and overall survival were comparable between arms, as was overall grade (G) ≥3 late toxicity (36% vs 20%; P = .1). More ≥G3 late mucosal ulcers were observed in active smokers (29% vs 3%; P = .005) and alcohol users (33% vs 13%; P = .02), independent of treatment arm. Similarly, in the A-DPBN arm, significantly more patients who smoked at diagnosis developed ≥G3 (46% vs 12%; P = .005) and ≥G4 (29% vs 8%; P = .048) mucosal ulcers. One arterial blowout occurred after a G5 mucosal toxicity. A-DPBN resulted in superior 1- and 2-year LC for HNC compared with S-IMRT. This supports further exploration in multicenter phase 3 trials. It will, however, be challenging to recruit a substantial patient sample for such trials, as concerns have arisen regarding the association of late mucosal ulcers when escalating the dose in continuing smokers.

A Prospective Study Assessing the Efficacy and Toxicity of Stereotactic Body Radiation Therapy for Oligometastatic Bone Metastases

PurposeStereotactic body radiation therapy (SBRT) is a promising treatment for oligometastatic disease in bone due to its delivery of high dose to target tissue and minimal dose to surrounding tissue. The purpose of this study is to assess the efficacy and toxicity of this treatment in patients with previously unirradiated oligometastatic bony disease. Materials and MethodsIn this prospective phase II trial, patients with oligometastatic bone disease, defined as ≤3 active sites of disease, were treated with SBRT at XXXX between December 2016 and May 2019. SBRT dose and fractionation regimen were not protocol-mandated. Local progression-free survival (LPFS), progression-free survival (PFS), prostatic specific antigen (PSA) progression, and overall survival (OS) were reported. Treatment-related toxicity was also reported. ResultsA total of 98 patients and 126 lesions arising from various tumor histologies were included in this study. The median age of patients enrolled was 72.8 years (80.6% male, 19.4% female). Median follow-up was 26.7 months. The most common histology was prostate cancer (68.4%, 67/98). The most common dose prescriptions were 27/30 Gy in 3 fractions (27.0%, 34/126), 30 Gy in 5 fractions (16.7%, 21/126), or 30/35 Gy in 5 fractions (16.7%, 21/126). Multiple doses per treatment regimen reflect dose painting employing the lower dose to the clinical target volume (CTV) and higher dose to the gross tumor volume (GTV). Four patients (4.1%, 4/98) experienced local progression at one site for each patient (3.2%, 4/126). Among the entire cohort, 2-year LPFS (including death without local progression) was 84.8%, 2-year PFS (including deaths as well as local, distant, and PSA progression) was 47.5%, and 2-year OS was 87.3%. Twenty-six patients (26.5%, 26/98) developed treatment-related toxicities. ConclusionsOur study supports existing literature in showing that SBRT is effective and tolerable in patients with oligometastatic bone disease. Larger phase III trials are necessary and reasonable to determine long-term efficacy and toxicities.

RADT-04. DOSE PAINTING WITH THE GAMMA KNIFE LIGHTNING OPTIMIZER TO ESCALATE RADIATION DOSE TO RESIDUAL TUMOR WITHIN BRAIN METASTASIS RESECTION CAVITIES

Abstract BACKGROUND The novel Gamma Knife (GK) Lightning optimizer allows simultaneous automated optimization of multiple intracranial radiotherapy targets. We used this optimizer to create a dose-painting treatment plan where an escalated dose was prescribed to residual disease within a brain metastasis resection cavity. We validated this method by measuring dose-delivery accuracy using radiochromic film in an anthropomorphic phantom. METHODS A 15.7cc irregular contour was drawn to represent a brain metastasis resection cavity, a 2mm expansion contour created, and a 1.6cc contour drawn representing a nodule of residual disease. In GammaPlan v11.3.1, three targets were created with overlapping dose matrices. Targets were prescribed 3Gy (2mm expansion), 4Gy (resection cavity), and 5Gy (residual disease) in one fraction. On the GK Icon system, an occipital mold was made, an unexposed film placed in the phantom’s cranium, cone-beam coregistration conducted, and treatment delivered. The film was scanned and calibrated for absolute dosimetry. To evaluate dose-painting accuracy, global gamma index (GI) analyses were performed at various dose and distance tolerances, excluding points below 30% of the maximum dose. RESULTS An 18-minute treatment plan with 40 shots was created and delivered. Prescription isodose lines were 3Gy at 55% (2mm expansion, mean 4.8Gy), 4Gy at 69% (resection cavity, mean 5.2Gy), and 5Gy at 75% (residual disease, mean 6.1Gy). All target volumes had ≥ 99% prescription dose coverage and the maximum dose was 6.9Gy. Paddick conformality indices were 0.79 (2mm expansion), 0.74 (resection cavity), and 0.15 (residual disease). Gamma index pass rate/mean GI/median GI were 73%/0.68/0.55 at 1%/1mm tolerance, 85%/0.58/0.48 at 2%/1mm tolerance, and 97%/0.34/0.28 at 2%/2mm tolerance. An average of 17,883 points were evaluated per analysis. CONCLUSIONS We successfully performed GK dose painting with the Lightning optimizer, verifying dose delivery within clinically acceptable tolerances. Future work is needed to determine optimal dose levels for use in clinical practice.

Impact of attenuation correction of radiotherapy hardware for positron emission tomography-magnetic resonance in ano-rectal radiotherapy patients.

Positron Emission Tomography-Magnetic Resonance (PET-MR) scanners could improve ano-rectal radiotherapy planning through improved Gross Tumour Volume (GTV) delineation and enabling dose painting strategies using metabolic measurements. This requires accurate quantitative PET images acquired in the radiotherapy treatmentposition. This study aimed to evaluate the impact on GTV delineation and metabolic parameter measurement of using novel Attenuation Correction (AC) maps that included the radiotherapy flat couch, coil bridge and anterior coil to see if they werenecessary. Seventeen ano-rectal radiotherapy patients received a -FluoroDeoxyGlucose PET-MR scan in the radiotherapy position. PET images were reconstructed without ( ) and with ( ) the radiotherapy hardware included. Both AC maps used the same Computed Tomography image for patient AC. Semi-manual and threshold GTVs were delineated on both PET images, the volumes compared and the Dice coefficient calculated. Metabolic parameters: Standardized Uptake Values , and Total Lesion Glycolysis (TLG) were compared using paired t-tests with a Bonferroni corrected significance level of . Differences in semi-manual GTV volumes between and were approaching statistical significance (difference , ), with larger differences in low FDG-avid tumours ( ). The and GTVs were concordant with Dice coefficients (manual) and (threshold). Metabolic parameters were significantly different, with , and TLG differences of ( ), ( ) and ( ) respectively. The TLG difference resulted in 1/8 rectal cancer patients changing prognosis group, based on literature TLG cut-offs, when using rather than . This study suggests that using AC maps with the radiotherapy hardware included is feasible for patient imaging. The impact on tumour delineation was mixed and needs to be evaluated in larger cohorts. However using AC of the radiotherapy hardware is important for situations where accurate metabolic measurements are required, such as dose painting and treatmentprognostication.

Plan robustness and RBE influence for proton dose painting by numbers for head and neck cancers

PurposeTo investigate the feasibility of dose painting by numbers (DPBN) with respect to robustness for proton therapy for head and neck cancers (HNC), and to study the influence of variable RBE on the TCP and OAR dose burden. Methods and materialsData for 19 patients who have been scanned pretreatment with PET-FDG and subsequently treated with photon therapy were used in the study. A dose response model developed for photon therapy was implemented in a TPS, allowing DPBN plans to be created. Conventional homogeneous dose and DPBN plans were created for each patient, optimized with either fixed RBE = 1.1 or a variable RBE model. Robust optimization was used to create clinically acceptable plans. To estimate the maximum potential loss in TCP due to actual SUV variations from the pre-treatment imaging, we applied a test case with randomized SUV distribution. ResultsRegardless of the use of variable RBE for optimization or evaluation, a statistically significant increase (p < 0.001) in TCP was found for DPBN plans as compared to homogeneous dose plans. Randomizing the SUV distribution decreased the TCP for all plans. A correlation between TCP increase and variance of the SUV distribution and target volume was also found. ConclusionDPBN for protons and HNC is feasible and could lead to a TCP gain. Risks associated with the temporal variation of SUV distributions could be mitigated by imposing minimum doses to targets. The correlation found between TCP increase and SUV variance and target volume may be used for patient selection.

Stability of metabolic tumor volume may enable radiotherapy dose painting in anal cancer

PurposeTo evaluate the variability of the 18F-FDG-PET/CT-based metabolic tumor volume (MTV) in anal cancers during fractionated chemoradiotherapy (CRT), and assess the impact of this variability on dosimetric accuracy in MTV-targeted dose painting. MethodsEleven patients with anal squamous cell carcinoma who received fractionated chemoradiotherapy with curative intent were included. 18F-FDG PET/CT images were acquired at pre- and mid-treatment. Target volumes and organs at risk (OARs) were contoured manually on both image series. The MTV was generated from the PET images by thresholding. Treatment plans were retrospectively optimized for both image series using volumetric modulated arc therapy (VMAT). Standard plans prescribed 48.6 Gy, 54 Gy and 57.5 Gy in 27 fractions to elective regions, lymph node metastases and primary tumor, respectively. Dose painting plans included an extra dose level of 65 Gy to the MTV. Pre-treatment plans were transferred and re-calculated at mid-treatment basis. ResultsMTV decreased from pre- to mid-treatment in 10 of the 11 patients. On average, 71 % of MTVmid overlapped with MTVpre. The median and mean doses to the MTV were robust against anatomical changes, but the transferred dose painting plans had lower D98% values than the original and re-optimized plans. No major differences were found between standard and dose painting plans for OARs. ConclusionsDespite volumetric changes in the MTV, adequate dose coverage was observed in most dose painting plans. The findings indicate little or no need for adaptive dose painting at mid-treatment. Dose painting appears to be a safe treatment alternative with similar dose sparing of OARs.

Dose Painting Radiotherapy Guided by Diffusion-Weighted Magnetic Resonance vs. 18F-FDG-PET/CT in Locoregionally Advanced Nasopharyngeal Carcinoma: A Randomized, Controlled Clinical Trial

This phase II randomized controlled trial aimed at comparing the efficacy and toxicity of diffusion-weighted magnetic resonance imaging (DWI)-guided dose painting radiotherapy (DP-RT), FDG-PET/CT-guided DP-RT, and conventional MRI-based radiotherapy (RT) in locoregionally advanced nasopharyngeal carcinoma (NPC). A total of 330 patients with stage III-IVa NPC disease were randomly assigned in a 1:1:1 ratio to receive induction chemotherapy followed by concurrent chemoradiotherapy by DWI-guided DP-RT (group A, n = 110), FDG-PET/CT-guided DP-RT (group B, n = 110), or conventional MRI-based RT (group C, n = 110). All patients received volumetric modulated arc therapy (VMAT). In group A, subvolume GTVnx-DWI (gross tumor volume of nasopharynx in DWI) was defined as the areas within the GTVnx (gross tumor volume of nasopharynx) with an apparent diffusion coefficient (ADC) below the mean ADC (ADC < mean). In group B, subvolume GTVnx-PET (gross tumor volume of nasopharynx in PET images) was defined within GTVnx as the SUV50%max isocontour. The doses to GTVnx-DWI in group A and GTVnx-PET in group B were escalated to 75.2 Gy/32 fx in patients with T1-2 disease and to 77.55 Gy/33 fx in those with T3-4 disease in 2.35 Gy per fraction. In group C, planning gross tumor volume of nasopharynx (PGTVnx) was irradiated at 70.4 to 72.6 Gy/32 to 33 fx in 2.2 Gy per fraction. This trial is registered with chictr.org.cn (ChiCTR2200057476). Group A and B showed significant higher complete response (CR) rates than group C (100%, 100%, and 96.4% for group A, B and C, respectively, p = 0.036). In groups A, B and C, the 1-year local recurrence-free survival (LRFS) rates were 100%, 100%, and 94.5%, respectively (p = 0.002). The 1-year disease-free survival (DFS) rates were 100%, 99.1%, and 92.7%, respectively (p = 0.001). The 1-year distant metastasis-free survival (DMFS) rates were 100%, 99.1%, and 93.6%, respectively (p = 0.004). The 1-year overall survival (OS) rates were 100%, 100%, and 95.4%, respectively (p = 0.006). Group A and B had significantly higher 1-year LRFS, DFS, DMFS, and OS than those in group C. No significant differences were observed in LRFS, DFS, DMFS and OS between group A and B. Group B (PET/CT group) had a higher incidence of grade 3-4 acute ototoxicity (3.6%) than group A (0%) and group C (0%, p = 0.036). No significant differences in other grade 3-4 acute adverse events and late toxic effects were observed among the three groups, and no patient had grade 5 toxicities. Multivariate analysis showed that dose painting (DWI-guided DP-RT and PET/CT-guided DP-RT vs conventional MRI-based RT) was associated with improved LRFS, DFS, DMFS and OS. Both DWI-guided DP-RT and PET/CT-guided DP-RT plus chemotherapy are associated with improved LRFS, DFS, DMFS and OS compared with conventional MRI-based RT among patients with locoregionally advanced NPC. DWI-guided DP-RT does not increase toxicities, but PET/CT-guided DP-RT has higher incidence of acute ototoxicity.

VMAT TBI Technique Using Autoplanning Scripts

Evident by the Children's Oncology Group (COG) survey of pediatric total body irradiation (TBI) practice, 100% of physicians were open to refining the conventional TBI technique to lower the lung dose and 75% of respondents were interested in implementing VMAT or a 3-D CRT and IMRT system TBI. Unfortunately, only a handful of COG institutions have implemented VMAT or Tomo TBI. We created the autoplanning scripts and shared them with the public to make the VMAT TBI more wide-spread. Here, we report on our initial experience of treating Stanford VMAT TBI technique using the scripts. From October 2019 to February 2023, 75 patients were treated with VMAT TBI at our institution. Organ sparing depended on the regimen: myeloablative (lungs, kidneys, and lenses); non-myeloablative (lungs, kidneys, lenses, gonads, brain, and thyroid). Treatment planning was performed using Eclipse Scripting Application Programming Interface (ESAPI) auto-planning scripts. Data on patient, treatment details, and dosimetric indices were collected. Treatment was delivered using IGRT for every isocenter and every fraction. In-vivo measurements were performed on the matchline between the VMAT and AP/PA fields and on the testes for the first fraction. Median patient age was 13 years (range, 1 - 64). The patient height and width range were 83.6-197.3 cm and 24.9-60.3 cm, respectively. Forty-eight percent of patients were treated using myeloablative and 52% nonmyeloablative regimens. For all patients the lungs, lungs-1cm, and kidneys Dmean were consistently spared to 59.8±4.7%, 43.0±6.5%, and 70.9±7.7% of the prescription dose, respectively. Gonadal sparing (Dmean = 31.5±5.9%) was achieved for all patients with benign disease. In addition, brain and thyroid was spared for these patients. For nine patients, VMAT TBI offered additional organ sparing (liver, heart, and previously irradiated areas) and possibility to perform the simultaneously integrated boost. The average PTV D1cc was 120.3±6.6% for all patients. PTV D1cc correlated with patient height and width (R2 = 0.62 and 0.53). Sixteen patients (21.3%) with height <116cm were treated with 3-isocenter VMAT only plans, 59 patients (78.6%) were treated with 3-4 isocenter VMAT plans in head-first-supine position and 1-3 AP/PA plan in feet-first-supine position. Rotational platform was used to change the patient orientation. The average matchline dose measurement indicated patient setup was reproducible (96.1±4.5% relative to planned dose). For the first 35 patients, treatment time, including patient setup and beam-on, was 47.5±9.5 min. VMAT TBI is a modern alternative to conventional 2D TBI treatment offering the possibility of organ sparing, dose painting, and accurate treatment using IGRT. The automated scripts enable streamline planning with consistent plan quality.