Clinical Target Volume Coverage Research Articles

Five-Fraction Proton Therapy for Chordomas and Chondrosarcomas of the Skull Base: Preliminary Results of a Prospective Series

To describe the first series of patients with clival chordomas and chondrosarcomas treated with extremely hypofractionated proton therapy in a single institution with focus on acute tolerance and dosimetric parameters. A total of 11 consecutive patients with biopsy proven chordomas and chondrosarcomas were prospectively included in a five-fraction proton therapy protocol between June 2022 and January 2023. The inclusion criteria for this protocol were: Age > 18 yo., Karnofsky Performance Status (KPS) ≥ 70%, absence of metastases, no previous radiation courses, clinical target volume (CTV) up to 50 cc and CTV location relative to organs at risk that allowed compliance with the necessary dose restrictions for hypofractionated treatments in 5 fractions, according to the international guidelines. Treatment was delivered with a Proteus®ONE cyclotron using Pencil Beam Scanning (PBS) Intensity-Modulated Proton Therapy (IMPT). Patient setup was performed with CBCT imaging at isocenter and X-Ray obliques, allowing a robust planning with 1 mm setup uncertainty and 3.5% range uncertainty. IMPT plans were obtained with RayStation employing 4 to 6 non-coplanar beams. In 7 patients' apertures were used in 2 of the beams, to reduce lateral penumbra and to optimize dose gradient. A total of 11 patients (7 males and 5 females) with an age range between 29 and 79 yo, were included. 6 patients with classic chordomas and 5 patients with grade I-II chondrosarcomas were treated with a total dose of 37.5 GyRBE and 35 GyRBE, respectively, in 5 daily fractions. All the patients had received previous surgery with complete resection in 2 patients, subtotal resection in 7 patients and partial resection in 2 patients. Most common symptoms at diagnosis were diplopia and headache and baseline median KPS after surgery was 90% (70 - 100%). Median CTV was 30.62 cc (10.56 - 47.47 cc). Median CTV coverage was V95% = D95.5%. Median maximal dose for the brainstem was 26.5 GyRBE (30 - 24.7 GyRBE) and for the optic pathway was 20.7 GyRBE (8.9 - 23.6 GyRBE). Median follow-up was 3 months (8 - 1 months). Acute toxicity during follow-up was mild, with grade I - II headache (64%), grade I asthenia (45%), grade I nausea (27%), grade I dysphagia (18%) and reversible alopecia (45%). Only one patient showed nystagmus and mild loss of strength in left lower limb related with an ischemic brainstem lesion, in a low dose region, not clearly radiation related. 8 patients had a 3-month follow-up MRI with no signs of progression. Five-fraction proton therapy for the treatment of clival chordomas and chondrosarcomas is dosimetrically feasible and well tolerated for selected patients. Proton therapy remains a limited resource, consequently, reducing treatment time can have significant financial and psychosocial implications. Longer follow up is needed to validate these results.

Feasibility Study of Robust Treatment Planning in VMAT for Head and Neck Cancer

In general, patient positional uncertainty is considered by adding a geometrically expanded margin to clinical target volume (CTV) in photon radiation therapy. However, this method may not be suitable because image-guided radiotherapy is available. In intensity modulated proton beam therapy, robust treatment planning is currently common to take patient positional uncertainty into account in optimization rather than in margins. The purpose of this study is to assess the feasibility of clinical implementation of the method in volumetric modulated arc therapy (VMAT) for head and neck cancer. We quantitatively evaluated whether the plans with the robust optimization (Robust plans) can adequately cover CTV against patients' positional uncertainties and body shape change throughout a treatment course. Ten head and neck cancer patients were chosen, who were treated with PTV-based VMAT plans in our hospital between 2021.5-2022.4. RayStation V10A (RaySearch Laboratories, Stockholm, Sweden) was used for the robust optimization, which was applied to the CTVs with patient positional uncertainty of 5 mm in the 6-axis direction. Dose prescribed to the high- and low-risk CTVs were to 70 and 56 Gy in 35 fractions, respectively. To create the patients' CT images with residual set-up errors and body shape change at the treatment, pseudo simulation-CT images were created by deformable image registration with CBCT and simulation-CT. Dose distribution at the treatment was re-calculated by applying the plan to the pseudo simulation-CT images. The variation of D98 for the high-risk CTV from the time of treatment planning was evaluated on a weekly basis. For comparison, planning target volume (PTV) -based plans (5 mm margin circumference) were created and a similar evaluation was performed. D98 for the high-risk CTV varied between -3∼2% in the robust plan and between -5∼1% in the PTV-based plan during the treatment course. There was no significant difference in the amount of D98 variation between the two plans by t-test, except for one case with hypopharyngeal cancer. In this case, D98 for the high-risk CTV varied within ±1% with the PTV-based plan, whereas the value decreased up to 3% with the robust plan (p < 0.05). This case often had a residual setup error of approximately 5 mm at the sites related to the pitch rotation of head, suggesting that the dose distribution for the robust plan was affected by non-rigid positional errors. Patient weight loss during the treatment period was -3.5±2.4 kg, showing a weak correlation (r = -0.33) with the variation in D98 for the high-risk CTV. The robust treatment planning exhibits comparable CTV coverage to the conventional PTV-based planning against positional uncertainty and body shape change throughout a treatment period. In order to overcome set-up baseline shift by the non-rigid positional errors, re-planning should be recommended. Further planning studies will be conducted to promote clinical implementation of the method.

Characterization of Photon Intensity Modulated Radiation Therapy Robustness in Patients With Prostate Cancer as a Proposed Benchmark for Proton Therapy Robustness Evaluation

Robustness evaluation is increasingly used in particle therapy planning to assess clinical target volume (CTV) coverage in the setting of setup and range uncertainty. However, no clear standard exists as to an acceptable degree of plan robustness. The aim of this study is to quantify x-ray robustness parameters, as this could inform proton planning when held to a similar standard. Consecutive patients with prostate adenocarcinoma treated with definitive x-irradiation to the prostate alone at a single institution in 2019 were retrospectively reviewed. CTV to planned target volume (PTV) margins of 7 mm in all directions, except 4 mm posteriorly, were used in the main cohort. Plans were normalized to PTV V100% ≥ 95%. Patient setup errors were simulated by shifting the isocenter relative to the patient in each of the cardinal directions. The magnitude of each shift equaled the magnitude of the CTV to PTV expansion in that direction. Range uncertainty was set to 0%. A total of 27 patients were evaluated. The mean (SD) nominal plan CTV V100% was 99.6% (1.1%). The mean (SD) worst-case shift CTV V100% was 97.2% (2.8%). The mean (SD) nominal and worst-case CTV V95% were 100% (0%) and 99.7% (0.5%), respectively. A worst-case CTV V100% > 90% and a worst-case CTV V95% > 99% were achieved in over 95% of plans. The mean (SD) nominal and worst-case rectal V70 Gy were 2.37 cc (1.00 cc) and 11.60 cc (3.16 cc), respectively. The mean (SD) nominal and worst-case bladder V60 Gy were 7.8% (4.8%) and 14.5% (9.3%), respectively. Paired 2-tailed t tests comparing the nominal to worst-case dose-volume histograms were significant for each dosimetric parameter (P < .01). X-ray planning uses PTV margins to inherently provide robustness to patient setup errors. Although the prostate remains well covered in various setup uncertainty scenarios, organs at risk routinely exceeded nominal treatment plan institutional constraints in the worst-case scenarios. Robustness metrics obtained from x-ray plans could serve as a benchmark for proton therapy robust optimization and evaluation.

A unified path seeking algorithm for IMRT and IMPT beam orientation optimization

Objective. Fully automated beam orientation optimization (BOO) for intensity-modulated radiotherapy and intensity modulated proton therapy (IMPT) is gaining interest, since achieving optimal plan quality for an unknown number of fixed beam arrangements is tedious. Fast group sparsity-based optimization methods have been proposed to find the optimal orientation, but manual tuning is required to eliminate the exact number of beams from a large candidate set. Here, we introduce a fast, automated gradient descent-based path-seeking algorithm (PathGD), which performs fluence map optimization for sequentially added beams, to visualize the dosimetric benefit of one added field at a time. Approach. Several configurations of 2–4 proton and 5–15 photon beams were selected for three head-and-neck patients using PathGD, which was compared to group sparsity-regularized BOO solved with the fast iterative shrinkage-thresholding algorithm (GS-FISTA), and manually selected IMPT beams or one coplanar photon VMAT arc (MAN). Once beams were chosen, all plans were compared on computational efficiency, dosimetry, and for proton plans, robustness. Main results. With each added proton beam, Clinical Target Volume (CTV) and organs at risk (OAR) dosimetric cost improved on average across plans by [1.1%, 13.6%], and for photons, [0.6%, 2.0%]. Comparing algorithms, beam selection for PathGD was faster than GS-FISTA on average by 35%, and PathGD matched the CTV coverage of GS-FISTA plans while reducing OAR mean and maximum dose in all structures by an average of 13.6%. PathGD was able to improve CTV [Dmax, D95%] by [2.6%, 5.2%] and reduced worst-case [max, mean] dose in OARs by [11.1%, 13.1%]. Significance. The benefit of a path-seeking algorithm is the beam-by-beam analysis of dosimetric cost. PathGD was shown to be most efficient and dosimetrically desirable amongst group sparsity and manual BOO methods, and highlights the sensitivity of beam addition for IMPT in particular.

Robust mixed electron-photon radiation therapy planning for soft tissue sarcoma.

Mixed electron-photon beam radiation therapy (MBRT) is an emerging technique in which external electron and photon beams are simultaneously optimized into a single treatment plan. MBRT exploits the steep dose falloff and high surface dose of electrons while maintaining target conformity by leveraging the sharp penumbra ofphotons. This study investigates the dosimetric benefits of MBRT for soft tissue sarcoma (STS)patients. A retrospective cohort of 22 STS of the lower extremity treated with conventional photon-based Volumetric Modulated Arc Therapy (VMAT) were replanned with MBRT. Both VMAT and MBRT treatments were planned on the Varian TrueBeam linac using the Millenium multi-leaf collimator. No electron applicator, cutout or additional collimating devices were used for electron beams of MBRT plans. MBRT plans were optimized to use a combination of 6 MV photons and five electron energies (6, 9, 12, 16, 20 MeV) by a robust column generation algorithm. Electron beams in this study were planned at standard 100 cm source-axis distance (SAD). The dose to the clinical target volume (CTV), bone, normal tissue strip and other organs-at-risk (OARs) were compared using a Wilcoxon signed-ranktest. As part of the original VMAT treatment, tissue-equivalent bolus was required in 10 of the 22 patients. MBRT plans did not require bolus by virtue of the higher electron entrance dose. CTV coverage by the prescription dose was found to be clinically equivalent between plans of either modality: (MBRT) = 97.9 ± 0.2% versus (VMAT) = 98.1 ± 0.6% (p=0.34). Evaluating the absolute paired difference between doses to OARs in MBRT and VMAT plans, we observed lower to normal tissue in MBRT plans by 14.9 ± 3.2% ( ). Similarly, to bone was found to be decreased by 8.2 ± 4.0% ( ) of the bonevolume. For STS with subcutaneous involvement, MBRT offers statistically significant sparing of OARs without sacrificing target coverage when compared to VMAT. MBRT plans are deliverable on conventional linacs without the use of electron applicators, shortened source-to-surface distance (SSD) or bolus. This study shows that MBRT is a logistically feasible technique with clear dosimetricbenefits.

CBCT-based deformable dose accumulation of external beam radiotherapy in cervical cancer

Background: Delivered radiotherapy doses do not exactly match those planned for a course of treatment, largely due to inter-fraction changes in anatomy. In this study, accumulated delivered dose was calculated for a sample of cervical cancer patients, by deformably registering daily cone beam computed tomography (CBCT) images to the planning computed tomography (CT) scan. Planned and accumulated doses were compared for the clinical target volume (CTV), bladder, and rectum. Material and Methods: For 10 patients receiving 45 Gy in 25 fractions of external beam radiotherapy, daily dose distributions were calculated on CBCT. These images were deformed onto the planning CT and the dose was accumulated using Velocity 4.1 (Varian Medical Systems, Palo Alto, USA). The quality of deformable image registration was evaluated visually and by calculating Dice similarity coefficients and mean distance to agreement. Results: V95%>99% was achieved for the primary CTV in 9/10 patients for the planned dose distribution and 7/10 patients for the accumulated dose distribution. Primary CTV coverage by 95% of the prescription dose was reduced in one patient, due to an increase in anterior-posterior separation. Comparison of planned and accumulated dose volume histograms (DVHs) for the bladder and rectum found agreement within 5% at low and intermediate doses, but differences exceeded 20% at higher doses. Direct addition of CBCT DVHs was seen to be a poor estimate for the accumulated DVH at higher doses. Conclusion: Computation of delivered radiotherapy dose that accounts for inter-fraction anatomical changes is important for establishing dose-effect relationships. Updating delivered dose distributions after each fraction would support informed clinical decision making on any potential treatment interventions.

In silico comparison of whole pelvis intensity-modulated photon versus proton therapy for the postoperative management of prostate cancer

Background Limited data exist comparing intensity-modulated photon (IMRT) and proton (IMPT) radiation therapy when treating the prostate bed and pelvic lymph nodes in the postoperative setting for prostate cancer. The aim of this study was to evaluate dosimetric differences between IMRT and IMPT when treating with whole pelvis radiation therapy (WPRT) postoperatively. Materials and methods IMRT and IMPT plans were generated for 10 post-prostatectomy patients treated between July and August 2020. The prescription was 50 Gy radiobiologic equivalent (GyE) (proton radiobiological effective dose 1.1) to the pelvis and 70 GyE to the prostate bed in 2 GyE per fraction. Paired 2-sided Wilcoxon signed-rank tests were used to compare clinical target volume (CTV) coverage and dose to organs at risk (OARs). Results CTV coverage was met for all plans with 99% of CTVs receiving ≥99% of prescription doses. Dose to OARs was significantly higher with IMRT than IMPT for the following endpoints: bladder V5-V65; bowel V5-V45; sigmoid V5-V50; rectum V5-V70; femoral head V40 and maximum dose; bone V5-V65. Select endpoints with significant differences included bladder V30 (63.5 vs. 44.4%, p < .001), bowel V15 (949 vs. 191 cc, p = .001) and V30 (386 vs. 121 cc, p < .001), rectum V40 (81.8 vs. 32.1%, p < .001) and V50 (47.6 vs. 24.9%, p < .001), femoral head maximum doses (46.4–47.1 vs. 38.3–38.6GyE, p < .001), and bone V10 (93.3 vs. 85.4%, p < . 001). Mean doses for all OARs were significantly higher with IMRT, including bladder (41.9 vs. 29.7GyE, p < .001), bowel (21.2 vs. 5.5GyE, p < .001), and rectum (50.8 vs. 27.3GyE, p < .001). Integral dose to ‘Body – CTV’ was significantly higher with IMRT (32.8 vs. 18.4 J, p < .001). Conclusion IMPT provides comparable target coverage to IMRT when treating prostate cancer with WPRT in the postoperative setting while significantly reducing dose to OARs. These data can inform the future clinical management and delivery of post-prostatectomy irradiation for prostate cancer.

Impact of Anatomical Position Errors on Dose Distribution in Head and Neck Radiotherapy and Robust Image Registration Against Anatomical Changes.

This study pursued two goals: Firstly, to search for anatomical structures strongly correlating with dose deterioration, and secondly to investigate the effectiveness of image registration focusing on critical anatomy by comparing it with a conventional method. The aim was to achieve robust image registration to correct for anatomical changes during treatment. Twenty patients with head and neck cancer were enrolled, and 68 simulation computed tomography (CT) and rescan CT image sets were retrospectively analyzed. Forty volumetric-modulated arc therapy and intensity-modulated proton therapy plans were generated and recalculated according to the rescan CT to evaluate the dose effects of anatomical changes. Correlation coefficients were calculated for the relationships between the six-axis motion of the anatomy and the dose indices for the clinical target volume (CTV) and organs at risk. In the image registration, we compared a conventional method and target-based registration that limited the registration range to the CTV and vertebrae. The CTV coverage and spinal cord dose were correlated with the position error associated with the pitch and vertical position of the vertebrae, and the parotid gland and oral cavity dose were strongly correlated with the position error associated with the roll of the clivus and mandible. The target registration improved CTV coverage and suppressed the increase in dose to organs at risk compared with conventional methods. Monitoring vertebral alignment, the assessment and correction of positioning errors associated with the clivus and mandible position errors are important to ensure the quality of daily treatment. Target-based registration may allow for more robust image registration.

Dosimetric Comparison of Intensity-Modulated Radiation Therapy (IMRT) and Intensity-Modulated Proton Therapy (IMPT) for a Novel Oral Tongue Avoidance Concept in Low-Risk Squamous Cell Carcinoma of the Oral Tongue.

After adequate surgical resection, early-stage oral tongue cancer patients can harbor a low risk of local recurrence but remain at risk of regional recurrence. Oral tongue avoidance during adjuvant radiation therapy is an attractive potential treatment strategy to mitigate treatment toxicity. We sought to quantify the dosimetric advantages of this approach and hypothesized that intensity-modulated proton therapy (IMPT) may further reduce organs at risk doses compared with intensity-modulated radiation therapy (IMRT). Five patients with oral tongue cancer treated with postoperative radiation therapy from August 2020 to September 2021 were retrospectively reviewed. Novel clinical target volume contours, excluding the oral tongue, were generated while maintaining coverage of bilateral at-risk lymph nodes. Comparison IMRT (X) and IMPT (PBT) plans were generated using standard treatment volumes (control) and avoidance volumes (study) (n = 4 plans/patient). Dosimetric variables for organs at risk were compared using the paired t test. The prescribed dose was 60 Gy in 30 fractions. D95% clinical target volume coverage was similar between X and PBT plans for both control and study clinical target volumes. Comparing control with study plans, both X (58.9 Gy vs 38.3 Gy, P = .007) and PBT (60.2 Gy vs 26.1 Gy, P < .001) decreased the oral cavity dosemean. The pharyngeal constrictor dosemean was also reduced (P < .003). There was no difference between control and study plans for larynx (P = .19), parotid (P = .11), or mandible dose (P = .59). For study plans, PBT significantly reduced oral cavity dosemean (38.3 Gy vs 26.1 Gy, P = .007) and parotid dosemean (23.3 Gy vs 19.3 Gy, P = .03) compared with X. For control plans, there was no difference in oral cavity dosemean using PBT compared with X, but PBT did improve the parotid dosemean (26.6 Gy vs 19.7 Gy, P = .02). This study quantifies the feasibility and dosimetric advantages of oral tongue avoidance while still treating the at-risk lymph nodes for oral tongue cancer. The dosimetric difference between PBT and X was most prominent with an oral tongue-avoidance strategy.

68Ga-PSMA PET/CT-Based Atlas for Prostate Bed Recurrence After Radical Prostatectomy: Clinical Implications for Salvage Radiation Therapy Contouring Guidelines.

The aim of this study was to analyze the patterns of prostate bed (PB) recurrence in prostate cancer patients experiencing prostate-specific antigen (PSA) persistence (BCP) or biochemical recurrence (BCR) after radical prostatectomy using 68Ga-PSMA-11 PET/CT (68Ga-PSMA PET) in relation to the Radiation Therapy Oncology Group (RTOG) clinical target volumes (CTVs). Methods: This single-center, retrospective analysis included patients with BCP or BCR after radical prostatectomy and PB recurrence on 68Ga-PSMA PET. The PB recurrences were delineated by nuclear medicine physicians, the CTVs by radiation oncologists contouring guidelines on the 68Ga-PSMA PET, respectively, masked from each other. The coverage of the 68Ga-PSMA PET recurrence was categorized as PSMA recurrence completely covered, partially covered, or not covered by the RTOG-based CTV. Further, we evaluated the differences in PSMA recurrence patterns among patients with different 68Ga-PSMA PET staging (miTNM). Mann-Whitney U tests, the chi-square test, and Spearman (ρ) correlation analysis were used to investigate associations between CTV coverage and 68Ga-PSMA PET-based tumor volume, serum PSA levels, miTNM, and rectal/bladder involvement. Results: A total of 226 patients were included in the analysis; 127 patients had PSMA recurrence limited to the PB (miTrN0M0), 30 had pelvic nodal disease (miTrN1M0), 32 had extrapelvic disease (miTrN0M1), and 37 had both pelvic nodal disease and extrapelvic disease (miTrN1M1). In the miTrN0M0 cohort, the recurrence involved the rectal and bladder walls in 12 of 127 (9%) and 4 of 127 (3%), respectively. The PSMA-positive PB recurrences were completely covered by the CTV in 68 of 127 patients (53%), partially covered in 43 of 127 (34%), and not covered in 16 of 127 (13%). Full coverage was associated with a smaller tumor volume (P = 0.043), a lack of rectal/bladder wall involvement (P = 0.03), and lower miTNM staging (P = 0.035) but not with lower serum PSA levels (P = 0.979). Conclusion: Our study suggests that 68Ga-PSMA PET can be a valuable tool for guiding salvage radiation therapy (SRT) planning directed to the PB in the setting of postoperative BCR or BCP. These data should be incorporated into the redefinition of PB contouring guidelines.

Robustness of VMAT to setup errors in postmastectomy radiotherapy of left-sided breast cancer: Impact of bolus thickness.

Volumetric modulated arc therapy (VMAT) with varied bolus thicknesses has been employed in postmastectomy radiotherapy (PMRT) of breast cancer to improve superficial target coverage. However, impact of bolus thickness on plan robustness remains unclear. The study enrolled ten patients with left-sided breast cancer who received radiotherapy using VMAT with 5 mm and 10 mm bolus (VMAT-5B and VMAT-10B). Inter-fractional setup errors were simulated by introducing a 3 mm shift to isocenter of the original plans in the anterior-posterior, left-right, and inferior-superior directions. The plans (perturbed plans) were recalculated without changing other parameters. Dose volume histograms (DVH) were collected for plan evaluation. Absolute dose differences in DVH endpoints for the clinical target volume (CTV), heart, and left lung between the perturbed plans and the original ones were used for robustness analysis. VMAT-10B showed better target coverage, while VMAT-5B was superior in organs-at-risk (OARs) sparing. As expected, small setup errors of 3 mm could induce dose fluctuations in CTV and OARs. The differences in CTV were small in VMAT-5B, with a maximum difference of -1.05 Gy for the posterior shifts. For VMAT-10B, isocenter shifts in the posterior and right directions significantly decreased CTV coverage. The differences were -1.69 Gy, -1.48 Gy and -1.99 Gy, -1.69 Gy for ΔD95% and ΔD98%, respectively. Regarding the OARs, only isocenter shifts in the posterior, right, and inferior directions increased dose to the left lung and the heart. Differences in VMAT-10B were milder than those in VMAT-5B. Specifically, mean heart dose were increased by 0.42 Gy (range 0.10 ~ 0.95 Gy) and 0.20 Gy (range -0.11 ~ 0.72 Gy), and mean dose for the left lung were increased by 1.02 Gy (range 0.79 ~ 1.18 Gy) and 0.68 Gy (range 0.47 ~ 0.84 Gy) in VMAT-5B and VMAT-10B, respectively. High-dose volumes in the organs were increased by approximate 0 ~ 2 and 1 ~ 3 percentage points, respectively. Nevertheless, most of the dosimetric parameters in the perturbed plans were still clinically acceptable. VMAT-5B appears to be more robust to 3 mm setup errors than VMAT-10B. VMAT-5B also resulted in better OARs sparing with acceptable target coverage and dose homogeneity. Therefore 5 mm bolus is recommended for PMRT of left-sided breast cancer using VMAT.

Dosimetric impact of applying a model-based dose calculation algorithm for skin cancer brachytherapy (interventional radiotherapy).

Brachytherapy (BT, interventional radiotherapy) is a well-established radiotherapy technique capable of delivering high doses to tumors while sparing organs at risk (OARs). Currently, the clinically accepted dose calculation algorithm used is TG-43. In the TG-186 report, new model-based dose calculation algorithms (MBDCA), such as Elekta's advanced collapsed cone engine (ACE), have been introduced, although their clinical application is yet to be fully realized. This study aimed to investigate two aspects of TG-186: firstly, a comparison of dose distributions calculated with TG-43 and TG-186 for skin tumors; and secondly, an exploration of the impact of using a water bolus on the coverage of clinical target volume (CTV) and OARs. Ten treatment plans for high-dose-rate IRT were developed. All plans were initially calculated using the TG-43 algorithm, and were subsequently re-calculated with TG-186. In addition, one of the treatment plans was assessed with both TG-43 and TG-186, using 10 different water bolus thicknesses ranging from 0 to 5 cm. To assess dose variations, the following dose-volume histogram (DVH) parameters were compared: D2cc and D0.01cc for OARs, and V150, V100, V95 and V90 for CTV coverage. The average dosimetric results for CTV and OARs, as calculated by both algorithms, revealed statistically significant lower values for TG-186 when compared with TG-43. The presence of a bolus was observed to enhance CTV coverage for the TG-186 algorithm, with a bolus thickness of 2 cm being the point at which ACE calculations matched those of TG-43. This study identified significant differences in dosimetric parameters for skin tumors when comparing the TG-43 and TG-186 algorithms. Moreover, it was demonstrated that the inclusion of a water bolus increased CTV coverage in TG-186 calculations.

Multilayer intensity modulated contact interventional radiotherapy (brachytherapy): Stretching the therapeutic window in skin cancer.

Interventional radiotherapy (IRT, brachytherapy) is a highly effective treatment method for non-melanoma skin cancer (NMSC). Traditionally, the maximum depth of NMSC lesions considered eligible for contact IRT was 5 mm; however, following several national surveys and recent recommendations, such cut-off, lesions thicker than 5 mm may be treated by contact IRT. The use of image guidance in defining the actual depth in treating NMSC to correctly identify clinical target volume (CTV) and prevent unnecessary toxicity is of paramount importance. The aim of the paper was to describe a multilayer arrangement of catheters to treat NMSC lesions thicker than 5 mm, thus proposing an example of dynamic intensity modulated IRT, using different catheter-to-skin distance of sources to reach the best CTV coverage and maximally reduce the excess of dose to the skin.

Comparing Ultra-hypofractionated Proton versus Photon Therapy in Extremity Soft Tissue Sarcoma.

Recent single institution, phase II evidence has demonstrated the feasibility and efficacy of ultra-hypofractionated, preoperative photon therapy in 5 fractions for the treatment of soft tissue sarcoma (STS). Our purpose was to evaluate the dosimetric benefits of modern scanning beam proton therapy compared with conventional photon radiation therapy (RT) for the neoadjuvant treatment of adult extremity STS. Existing proton and photon plans for 11 adult patients with STS of the lower extremities previously treated preoperatively with neoadjuvant RT at our center were used to create proton therapy plans using Raystation Treatment Planning System v10.A. Volumes were delineated, and doses reported consistent with International Commission on Radiation Units and Measurements reports 50, 62, and 78. Target volumes were optimized such that 100% clinical target volume (CTV) was covered by 99% of the prescription dose. The prescribed dose was 30 Gy for PT and RT delivered in 5 fractions. For proton therapy, doses are reported in GyRBE = 1.1 Gy. The constraints for adjacent organs at risk (OARs) within 1 cm of the CTV were the following: femur V30Gy ≤ 50%, joint V30Gy < 50%, femoral head V30Gy ≤ 5 cm3, strip V12 ≤ 10%, and skin V12 < 50%. Target coverage goals, OAR constraints, and integral dose were compared by Student t test with P < .05 significance. A minimum 99% CTV coverage was achieved for all plans. OAR dose constraints were achieved for all proton and photon plans; however, mean doses to the femur (10.7 ± 8.5 vs 16.1 ± 7.7 GyRBE), femoral head (2.0 ± 4.4 vs 3.6 ± 6.4 GyRBE), and proximal joint (1.8 ± 2.4 vs 3.5 ± 4.4 GyRBE) were all significantly lower with PT vs intensity-modulated radiation therapy (IMRT) (all P < .05). Integral dose was significantly reduced for proton vs photon plans. Conformity and heterogeneity indices were significantly better for proton therapy. Proton therapy maintained target coverage while significantly reducing integral and mean doses to the proximal organs at risk compared with RT. Further prospective investigation is warranted to validate these findings and potential benefit in the management of adult STS.

Dosimetric impact of rotational set-up errors in high-risk prostate cancer

Abstract Introduction: Cone-beam computed tomography (CBCT) provides an excellent solution to quantitative assessment and correction of patient set-up errors during radiotherapy. However, most linear accelerators are equipped with conventional therapy tables that can be moved in three translational directions and perform only yaw rotation. Uncorrected roll and pitch result in rotational set-up errors, particularly when the distance from the isocenter to the target border is large. The aim of this study was to investigate the impact of rotational errors on the dose delivered to the clinical target volume (CTV), the planning target volume (PTV) and organs at risk (OAR). Material and methods: 30 patients with prostate cancer treated with VMAT technique had daily CBCT scans (840 CBCTs in total) prior to treatment delivery. The rotational errors remaining after on-line correction were retrospectively analysed. The sum plans simulating the dose distribution during the treatment course were calculated for selected patients with significant rotational errors. Results: The dose delivered to the prostate bed CTV reported in the sum plan was not lower than in the original plan for all selected patients. For four patients from the selected group, the D98% for prostate bed PTV was less than 95%. The V47.88Gy for pelvic lymph nodes PTV was less than 98% for two of the selected patients. Conclusions: The analysis of the dosimetric parameters showed that the impact of uncorrected rotations is not clinically significant in terms of the dose delivered to OAR and the dose coverage of CTV. However, the PTV dose coverage is correlated with distance away from the isocenter and is smaller than planned.

Spare the Bowel, Don't Spoil the Target: Optimal Margin Assessment for Online Cone Beam Adaptive Radiation Therapy (OnC-ART) of the Cervix

PurposeThe standard treatment for locally advanced cervical cancer involves pelvic chemoradiation. Intensity modulated radiation therapy planning requires expansion of the cervix and uterus clinical target volume (CTV) by 1.5 to 2 cm to account for motion. With online cone beam adaptive radiation therapy (OnC-ART), interfractional movement is accounted for, which can potentially lead to smaller CTV to planned target volume (PTV) margins. In this study, we attempted to determine the optimal CTV-to-PTV margin for adequate coverage with OnC-ART and factors that can affect CTV coverage. Methods and MaterialsA retrospective cohort of 21 patients with cervical cancer treated with definitive chemoradiation was included. Nine patients treated with nonadaptive radiation had the uterocervix contoured on pretreatment cone beam computed tomography (CBCT) and end-treatment CBCTs. Anterior-posterior, lateral, and superior-inferior shifts and the average shift in all directions were calculated. A CTV-to-PTV expansion was determined and verified on a validation cohort of 12 patients treated with OnC-ART. ResultsThe average anterior-posterior, lateral, and superior-inferior shifts with standard deviation were 0.32 ± 1.55 cm, 0.12 ± 2.31 cm, and 1.67 ± 3.41 cm, respectively. A uniform 5-mm expansion around the pretreatment CTV covered 98.85% ± 1.23% of the end-treatment CTV. This 5-mm expansion was applied to our validation cohort treated with OnC-ART, and 98.39% ± 3.0% of the end-treatment CTV was covered. Time between CBCTs >30 minutes and change in bladder volume were significantly correlated to CTV coverage. ConclusionsBased on our analysis, a CTV-to-PTV margin of 5 mm is adequate to encompass 98% of the CTV. A significantly reduced margin could potentially decrease the toxicities associated with radiation for patients with cervical cancer and lead to improved patient reported toxicity outcomes. We recommend physicians begin with a 5-mm margin and assess adequate coverage with image guidance during daily adaptation.

AI-Based Auto-Segmentation for Loco-Regional Breast Cancer Radiotherapy: Training, Validation and Clinical Implementation

<h3>Purpose/Objective(s)</h3> To train and validate a comprehensive deep-learning (DL) segmentation model for loco-regional breast cancer with the aim of clinical implementation. <h3>Materials/Methods</h3> 200 left-sided breast cancer cases from two radiotherapy centers in Norway were included in the project. In all cases, 7 clinical target volumes (CTVs) were manually delineated based on the ESTRO guidelines, in addition to 11 organs at risk (OARs). 170 patient cases were used for training, which involved neural networks of 3D CNN U-net type. The remaining 30 cases were used for model validation, which included: 1) evaluation of geometric similarity between DL structures and manually delineated structures using 95-percentile Hausdorff distance (HD95) and Dice similarity coefficient (DSC), benchmarked against inter-observer variation (IOV), 2) qualitative scoring using a 4-step scale according to clinical usability, and 3) dosimetric analysis of conformal treatment plans which were based on uncorrected DL structures. A dedicated team of 3 experienced oncologists (EO) and 3 experienced radiation therapists contributed to the manual delineations for model training and validation, while 5 EOs delineated the same 5 patient cases for evaluation of IOV. To test for difference in model performance and IOV, Mann-Whitney U test was used, while paired sample T-test was used for the dosimetric analysis of OARs. <h3>Results</h3> Geometrically, the model performed better than IOV for all CTVs and most OARs, see Table 1 for main results. Qualitatively, no or only minor corrections were required for 14 % and 71 % of the CTVs and 72 % and 26 % of the OARs, respectively. Major corrections were required for 15 % of the CTVs and 2 % of the OARs, while no structure scored as "not usable". The most frequent corrections were adjustments in the cranial and caudal parts of the structures. Dosimetrically, the CTV coverage, based on D98 > 95 %, was fulfilled for 100 % and 89 % of the breast and lymph node structures, respectively. No differences in OAR dose parameters were considered clinically relevant. The model was implemented in a commercial treatment planning system, which generates the structures in 1.5 minutes. <h3>Conclusion</h3> Convincing results from the validation process led to the decision of clinical implementation. The model is now in clinical use, and will be monitored regarding applicability, standardization and efficiency. Table 1. Geometric performance of the DL model and corresponding IOV for all CTVs and two of the OARs (median values). Bold type indicates the best metric, and underscore indicate statistical significance (p<0.05).

Dosimetric Implications of Margin-Reduced MRI-Guided Stereotactic Body Radiotherapy to the Prostate Bed Following Radical Prostatectomy: Post-Hoc Analysis of a Phase II Study

<h3>Purpose/Objective(s)</h3> Due to the highly deformable and mobile nature of the target volume and adjacent organs at risk (OARs), generous planning target volume (PTV) margins have historically been used in the context of radiotherapy after radical prostatectomy. MRI-guided radiotherapy systems have improved on-board imaging capabilities and the ability to perform automatic beam holds based on pre-specified structures. Herein, we evaluate the dosimetric implications of interfraction variations in the clinical target volumes (CTV) and OARs in patients receiving margin-reduced MRI-guided stereotactic body radiotherapy (SBRT) to the prostate bed. <h3>Materials/Methods</h3> 31 consecutive patients received MRI-guided SBRT to the prostate bed (30 – 34 Gy in 5 fractions) without adaptive planning on a phase II study. The OAR volumes, CTV, and PTV (created using a 3 mm isotropic expansion of the CTV) were retrospectively contoured on on-board 0.35T MRIs obtained prior to each fraction (n=155). Geometric comparisons were made between the initial planning contours and the 5 daily contours for each patient using change in volume and Dice similarity coefficient (DSC) calculations. Coverage of the CTV and PTV was assessed (CTV V95% >93% and PTV V95% >90%), as were bladder and rectal dose constraints (Bladder Dmax <36.7 Gy, Bladder V32.5 Gy <35%, Rectum Dmax <36.7 Gy, Rectum V27.5 Gy <45%, Rectum 32.5 Gy <30%, and Rectal Wall V24 <50%). <h3>Results</h3> The median change in volume was -24.5% (interquartile range [IQR], -35.5 – -2.2%) for the bladder, 6.95% (IQR, -6.94 – 23.0%) for the rectum, -0.2% (IQR, -8.3 – 8.7%) for the rectal wall, 0.48% (IQR, -3.87 – 7.6%) for the CTV, and -0.48% (IQR, -5.12 – 6.53%) for the PTV. The median DSC was 0.79 (IQR, 0.73 – 0.84) for the bladder, 0.76 (IQR, 0.69 – 0.81) for the rectum, 0.35 (IQR, 0.28 – 0.44) for the rectal wall, 0.89 (IQR, 0.83 – 0.93) for the CTV, and 0.90 (IQR, 0.87 – 0.95) for the PTV. 145/155 fractions (93.5%) met the CTV V95% >93% target and 134/155 fractions (86.5%) met both the CTV V95% >93% and PTV V95% >90% targets. When calculated over 5 cumulative fractions, 29/31 patients (93.5%) met the CTV goal of V95% >93%. 62/155 fractions (40%) failed at least one OAR constraint. The mean number of fractions per patient that failed at least one OAR constraint was 2/5 (median, 1; range, 0 – 5). <h3>Conclusion</h3> With MRI-guidance, a reduction of the PTV margin to 3 mm isotropically allows for adequate CTV coverage in over 90% of patients without the need for adaptive planning. However, OAR constraints are not met in 40% of delivered fractions despite meeting all dose constraints at the time of treatment planning. Online dose prediction and, if indicated, adaptive radiotherapy can optimize this to allow for improved OAR protection and potentially allow for further reductions in the PTV expansion while maintaining adequate CTV coverage.

In Silico Dosimetric Comparison of Intensity-Modulated Proton Radiotherapy (IMPT) vs. Intensity-Modulated Photon Radiotherapy (IMRT) in the Preoperative Treatment of Retroperitoneal Sarcoma

<h3>Purpose/Objective(s)</h3> With the results of the randomized STRASS trial, the benefit of preoperative radiation has been called into question in the treatment of retroperitoneal sarcoma. Given the large amount of normal tissue which often resides in close proximity to retroperitoneal sarcomas, the risk of radiation-associated toxicity is substantial, with 77% of irradiated patients experiencing grade ≥3 lymphopenia in STRASS. The exit dose and integral exposure associated with photon irradiation limits its therapeutic ratio. Our purpose was to evaluate a dosimetric comparison between ultra-hypofractionated modern scanning beam intensity-modulated proton therapy (IMPT) and intensity-modulated photon radiotherapy (IMRT) for the preoperative treatment of retroperitoneal sarcoma. We hypothesized that IMPT would significantly reduce dose to the to the liver, bowel and kidneys without sacrificing clinical target volume (CTV) coverage. <h3>Materials/Methods</h3> Ultra-hypofractionated IMRT and IMPT plans were generated using TPS on 10 patients previously treated with conventionally fractionated preoperative photon irradiation for retroperitoneal sarcoma. The prescription was 25 Gy radiobiological equivalent (GyE) to the entire CTV and 30 GyE to the margin-at-risk (CTV_Boost), all in five fractions. IMPT doses are reported in GyE = 1.1 Gy. Target coverage goals, OAR constraints, and integral dose were compared by student T-test with <i>p</i> < .050 considered significant. <h3>Results</h3> Target coverage goals, OAR constraints, and integral dose are reported in Table 1. Mean dose to liver, bowel, and ipsilateral and contralateral kidneys were all significantly lower with IMPT than IMRT, as was integral dose. <h3>Conclusion</h3> IMPT maintained target coverage while significantly reducing integral dose and mean dose to nearby OARs compared to IMRT. Further investigation is warranted to validate these dosimetric findings and potential clinical benefit in the management of retroperitoneal sarcoma.

Verification Studies Confirm Reproducibility of Post-Hysterectomy Pelvic Proton Radiotherapy

<h3>Purpose/Objective(s)</h3> Post-hysterectomy radiotherapy (RT) is associated with urinary, gastrointestinal, and hematologic toxicity. Concern for organ and target motion has limited exploration of proton RT as a tool to reduce toxicity. Attention to planning and treatment delivery is paramount given sensitivity of protons to small changes in soft tissue in the beam path. We sought to evaluate the consistency of target coverage and organ at risk (OAR) sparing in post-hysterectomy proton RT. <h3>Materials/Methods</h3> The first 10 patients treated with proton RT on an institutional prospective non-randomized trial of proton post-hysterectomy RT for endometrial cancer were included. CT simulation was performed with pelvic immobilization and a rectal balloon, which was also used for treatment. Full and empty bladder and IV contrast scans were obtained. Clinical target volumes (CTV) included the vaginal cuff, proximal 3 cm of vagina, and pelvic lymph nodes to the level of L4/L5. Prescription was 45 Gy (relative biological effectiveness (RBE) 1.1) in 25 fractions. Planning was multi-field optimization with two posterior oblique beams and a posterior beam. Plans were evaluated for robustness to ensure CTV coverage in worst case scenarios of ±5 mm isocenter shifts in x, y, and z directions and ±5% range uncertainty. A variable RBE calculation assuming a linear relationship between RBE and linear energy transfer was used to evaluate for target coverage and increased RBE within OARs. If needed, the plan was modified to limit hot spots without compromising coverage in the calculation with uniform 1.1 RBE. Patients underwent weekly CT-on-rails verification scans. Target coverage and dose to OARs were assessed at each verification and replanning was done if target coverage or OAR constraints did not meet original planning objectives. <h3>Results</h3> The first patient on the study required replan after first verification due to excess air in the rectum at simulation and verification, resulting in rectum V30Gy 90% and V40Gy 81%. After replan, subsequent verifications met objectives. Subsequent patients were planned with air in the rectum or bowel accounted for by evaluation of plans with air overridden to HU = -300 to -450 and HU = 0. Target coverage met acceptable planning parameters in all cases (Table 1). There was no statistical difference in bladder mean, V30Gy, and V45Gy; sigmoid V45Gy; rectum mean, V30Gy, and V40Gy; and small bowel V40% and V45Gy. All patients were successfully treated with protons for all planned fractions. <h3>Conclusion</h3> Proton post-hysterectomy pelvic RT with robust optimization is feasible, reproducible, and associated with appropriate target coverage and acceptable dose to organs at risk as assessed with weekly verification scans.