Local control of 1–5 fraction radiotherapy regimens for spinal metastases: an analysis of the impacts of biologically effective dose and primary histology

BackgroundThis analysis evaluates the impacts of biologically effective dose (BED) and histology on local control (LC) of spinal metastases treated with highly conformal radiotherapy to moderately-escalated doses.Materials and methodsPatients were treated at two institutions from 2010–2020. Treatments with less than 5 Gy per fraction or 8 Gy in 1 fraction were excluded. The dataset was divided into three RPA classes predictive of survival (1). The primary endpoint was LC.Results223 patients with 248 treatments met inclusion criteria. Patients had a median Karnofsky Performance Status (KPS ) of 80, and common histologies included breast (29.4%), non-small cell lung cancer (15.7%), and prostate (13.3%). A median 24 Gy was delivered in 3 fractions (BED: 38.4 Gy) to a median planning target volume (PTV) of 37.3 cc. 2-year LC was 75.7%, and 2-year OS was 42.1%. Increased BED was predictive of improved LC for primary prostate cancer (HR = 0.85, 95% CI: 0.74–0.99). Patients with favorable survival (RPA class 1) had improved LC with BED ≥ 40 Gy (p = 0.05), unlike the intermediate and poor survival groups. No grade 3–5 toxicities were reported.ConclusionsModerately-escalated treatments were efficacious and well-tolerated. BED ≥ 40 Gy may improve LC, particularly for prostate cancer and patients with favorable survival.     

Stereotactic body radiation therapy (SBRT) of adrenal gland metastases in oligometastatic and oligoprogressive disease

BackgroundStereotactic body radiation therapy (SBRT) as a form of noninvasive treatment that is becoming increasingly used to manage cancers with adrenal gland metastases. There is a paucity of data on safety and efficacy of this modality. The aim of the study was to evaluate the safety and efficacy of adrenal gland SBRT in oligometastatic and oligoprogressive disease.Materials and methodsIn this retrospective study, we performed a single-institution analysis of 26 adrenal lesions from 23 patients with oligometastatic or oligoprogressive disease treated from 2013 to 2019 with the goal of achieving durable local control. Palliative cases were excluded. Radiation dosimetry data was collected. Kaplan Meier product estimator and Cox proportional hazards regression analysis were used for statistical analysis.ResultsThe median dose was 36 Gy in 3 fractions (range: 24–50 Gy and 3–6 fractions) with a median biologically effective dose (BED10) of 72 (range: 40–100). 1-year local control rate was 80% and median local control was not achieved due to a low number of failures. 1- and 2-year overall survival rates were 66% and 32%. Toxicity was mild with only one case of grade 2 nausea and no grade 3–5 toxicity. Higher neutrophil to lymphocyte ratio was associated with worse overall survival and a trend toward worse progression-free survival. In addition, worse performance status and lower BED10 were associated with worse survival. No such association could be shown for primary tumor location, histology, size or stage.ConclusionAdrenal SBRT for oligometastatic or oligoprogressive disease is a safe and effective form of treatment.     

Dependence of the safe rectum dose on the CTV–PTV margin size and treatment technique

Background

Late rectal injury is a common side effect of external beam radiotherapy for prostate cancer.

Aim

The aim of this study was to evaluate what total dose may be safely delivered for prostate patients for 3DCRT and IMRT techniques and the CTV–PTV margin.

Materials and methods

3DCRT and IMRT plans were prepared for 12 patients. For each patient PTV was defined with CTV–PTV margins of 0.4, 0.6, …, 1.0 cm, and total doses of 70, 72, …, 80 Gy, with 2 Gy dose fraction. NTCP values for the rectum were calculated using the Lyman model. Both techniques were compared in terms of population mean DVH.

Results

Significantly smaller NTCPs for IMRT were obtained. For both techniques diminishing the margin CTV–PTV of 2 mm leads to decreasing the NTCP of about 0.03. For total dose of 80 Gy the NTCP was smaller than 10% for the 4 mm margin only. The QUANTEC dose volume constraints were more frequently fulfilled for the IMRT technique than for the 3DCRT technique.

Conclusions

The IMRT technique is safer for prostate patients than the 3DCRT. If very high total doses are applied the CTV–PTV margin of 0.4 cm and the IMRT technique should be used. If the CTV–PTV margin of 0.6 cm is applied, the NTCP is smaller than 10% for the 3DCRT and IMRT techniques for the total doses smaller than 74 Gy and 78 Gy, respectively.     

Advanced dose calculation algorithms in lung cancer radiotherapy: Implications for SBRT and locally advanced disease in deep inspiration breath hold

PurposeEvaluating performance of modern dose calculation algorithms in SBRT and locally advanced lung cancer radiotherapy in free breathing (FB) and deep inspiration breath hold (DIBH).MethodsFor 17 patients with early stage and 17 with locally advanced lung cancer, a plan in FB and in DIBH were generated with Anisotropic Analytical Algorithm (AAA). Plans for early stage were 3D-conformal SBRT, 45 Gy in 3 fractions, prescribed to 95% isodose covering 95% of PTV and aiming for 140% dose centrally in the tumour. Locally advanced plans were volumetric modulated arc therapy, 66 Gy in 33 fractions, prescribed to mean PTV dose. Calculation grid size was 1 mm for SBRT and 2.5 mm for locally advanced plans. All plans were recalculated with AcurosXB with same MU as in AAA, for comparison on target coverage and dose to risk organs.ResultsLung volume increased in DIBH, resulting in decreased lung density (6% for early and 13% for locally-advanced group).In SBRT, AAA overestimated mean and near-minimum PTV dose (p-values < 0.01) compared to AcurosXB, with largest impact in DIBH (differences of up to 11 Gy). These clinically relevant differences may be a combination of small targets and large dose gradients within the PTV.In locally advanced group, AAA overestimated mean GTV, CTV and PTV doses by median less than 0.8 Gy and near-minimum doses by median 0.4–2.7 Gy.No clinically meaningful difference was observed for lung and heart dose metrics between the algorithms, for both FB and DIBH.ConclusionsAAA overestimated target coverage compared to AcurosXB, especially in DIBH for SBRT.     

Evaluation of the target dose coverage of stereotactic body radiotherapy for lung cancer using helical tomotherapy: A dynamic phantom study

AimTo evaluate the target dose coverage for lung stereotactic body radiotherapy (SBRT) using helical tomotherapy (HT) with the internal tumor volume (ITV) margin settings adjusted according to the degree of tumor motion.BackgroundLung SBRT with HT may cause a dosimetric error when the target motion is large.Materials and methodsTwo lung SBRT plans were created using a tomotherapy planning station. Using these original plans, five plans with different ITV margins (4.0–20.0 mm for superior-inferior [SI] dimension) were generated. To evaluate the effects of respiratory motion on HT, an original dynamic motion phantom was developed. The respiratory wave of a healthy volunteer was used for dynamic motion as the typical tumor respiratory motion. Five patterns of motion amplitude that corresponded to five ITV margin sizes and three breathing cycles of 7, 14, and 28 breaths per minute were used. We evaluated the target dose change between a static delivery and a dynamic delivery with each motion pattern.ResultsThe target dose difference increased as the tumor size decreased and as the tumor motion increased. Although a target dose difference of <5 % was observed at ≤10 mm of tumor motion for each condition, a maximum difference of -9.94 % ± 7.10 % was observed in cases of small tumors with 20 mm of tumor motion under slow respiration.ConclusionsMinimizing respiratory movement is recommended as much as possible for lung SBRT with HT, especially for cases involving small tumors.     

Characteristics and dosimetric impact of intrafraction motion during peripheral lung cancer stereotactic radiotherapy: is a second midpoint cone beam computed tomography of added value?

BackgroundIn our department, during lung stereotactic body radiation therapy (SBRT), all patients receive an intra-fractional midpoint cone beam computed tomography (CBCT). This study aimed to quantify the benefit of adding a second midpoint CBCT over a course of peripheral lung SBRT.Materials and methodsSix-hundred-sixty-four CBCTs from 166 patients were retrospectively analyzed. Treatments were based on the internal target volume (ITV) approach. An isotropic 0.5 cm margin was used to create the planning target volume (PTV) around the ITV. The prescribed dose was 48 Gy in 4 fractions to the PTV. Patients were divided into two groups: patients for whom the 3D-intra-fractional-variation (IFV) was < 0.5 cm (105 patients, low risk group) and patients with at least one 3D-IFV ≥ 0.5 cm (61 patients, high-risk group). Plans simulating the dosimetric impact of the IFV were created as follows: the original 2 arcs (ARC ) were copied into a new plan consisting of 4 times ARC 1 and 4 times ARC 2. The delivery of ARC 1 was always assumed to have occurred with the isocenter initially coordinated, whereas the positions of ARC 2 were modified for each arc by the measured the 3D-IFV.ResultsFor the PTV, we obtained: D99% (Gy) = 45.2 vs. 48.2 Gy (p < 0.0001); Dmean = 53 vs. 54 Gy (p < .0001) for the reconstructed vs. planned dose values, respectively. For the ITV, the changes are less pronounced: D99% (Gy) = 52.2 vs. 53.6 Gy (p = 0.0007); Dmean = 56 vs. 56.8 Gy (p = 0.0144). The V48 Gy(%)-ITV coverage did not statistically change between the delivered vs. planned dose (p = 0.1803). Regarding the organs at risk for both groups, dose-volume-histograms were near-identical.ConclusionWe demonstrated that a single CBCT is sufficient and reliable to manage the IFV during peripheral lung SBRT.     

Evaluation of volumetric modulated arc therapy (VMAT) — based total body irradiation (TBI) in pediatric patients

BackgroundThe dosimetric characterization of volumetric modulated arc therapy (VMAT)-based total-body irradiation (TBI) in pediatric patients is evaluated.Materials and methodsTwenty-two patients between the ages of 2 and 12 years were enrolled for VMAT-based TBI from 2018 to 2020. Three isocenters were irradiated over three overlapping arcs. While prescribing 90% of the TBI dose to the planning treatment volume (PTV), two fractions (2 Gy each) were delivered each day; hence 12 Gy was delivered in six fractions. During treatment optimization, the mean lung and kidney doses were set not to exceed 7 Gy and 7.5 Gy, respectively. The maximum lens dose was also set to less than 4 Gy. Patient quality assurance was carried out by comparing treatment planning system doses to the 3-dimensional measured doses by the ArcCHECK^® detector. The electronic portal imaging device (EPID) gamma indices were also obtained.ResultsThe average mean lung dose was 7.75 ± 0.18 Gy, mean kidney dose 7.63 ± 0.26 Gy, maximum lens dose 4.41 ± 0.39 Gy, and the mean PTV dose 12.69 ± 0.16 Gy. The average PTV heterogeneity index was 1.15 ± 0.03. Average differences in mean kidney dose, mean lung dose, and mean target dose were 2.79% ± 0.88, 0.84% ± 0.45 and 0.93% ± 0.47, respectively; when comparing planned and ArcCHECK^® measured doses. Only grade 1–2 radiation toxicities were recorded, based on CTCAE v5.0 scoring criteria.ConclusionsVMAT-TBI was characterized with good PTV coverage, homogeneous dose distribution, planned and measured dose agreement, and low toxicity.     

Determination of optimal planning target volume margins in patients with gynecological cancer

PurposeTo define optimal planning target volume (PTV) margins for intensity modulated radiotherapy (IMRT) ± knee-heel support (KHS) in patients treated with adjuvant radiotherapy.MethodsComputed tomography (CT) scans ± KHS of 10 patients were taken before and at 3rd and 5th week of treatment, fused and compared with initial IMRT plans.ResultsA PTV margin of 15 mm in anteroposterior (AP) and superoinferior (SI) directions and 5 mm in lateral directions were found to be adequate without any difference between ± KHS except for the SI shifts in CTV-primary at the 3rd week. Five mm margin for iliac CTV was found to be inadequate in 10–20% of patients in SI directions however when 7 mm margin was given for iliac PTV, it was found to be adequate. For presacral CTV, it was found that the most striking shift of the target volume was in the direction of AP. KHS caused significantly less volume of rectum and bladder in the treated volume.ConclusionsPTV margin of 15 mm in SI and AP, and 5 mm in lateral directions for CTV-primary were found to be adequate. A minimum of 7 mm PTV margin should be given to iliac CTV. The remarkable shifting in presacral CTV was believed to be due to the unforeseen hip malposition of obese patients. The KHS seems not to provide additional beneficial effect in decreasing the shifts both in CTV-primary and lymphatic, however it may have a beneficial effect of decreasing the OAR volume in PTV margins.     

Characterization of robust optimization for VMAT plan for liver cancer

PurposeWe investigated the feasibility of robust optimization for volumetric modulated arc therapy (VMAT) stereotactic body radiation therapy (SBRT) for liver cancer in comparison with planning target volume (PTV)-based optimized plans. Treatment plan quality, robustness, complexity, and accuracy of dose delivery were assessed.MethodsTen liver cancer patients were selected for this study. PTV-based optimized plans with an 8-mm PTV margin and robust optimized plans with an 8-mm setup uncertainty were generated. Plan perturbed doses were evaluated using a setup error of 8 mm in all directions from the isocenter. The dosimetric comparison parameters were clinical target volume (CTV) doses (D_98%, D_50%, and D_2%), liver doses, and monitor unit (MU). Plan complexity was evaluated using the modulation complexity score for VMAT (MCSv).ResultsThere was no significant difference between the two optimizations with respect to CTV doses and MUs. Robust optimized plans had a higher liver dose than did PTV-based optimized plans. Plan perturbed dose evaluations showed that doses to the CTV for the robust optimized plans had small variations. Robust optimized plans were less complex than PTV-based optimized plans. Robust optimized plans had statistically significant fewer leaf position errors than did PTV-based optimized plans.ConclusionsComparison of treatment plan quality, robustness, and plan complexity of both optimizations showed that robust optimization could be feasibile for VMAT of liver cancer.     

Setup accuracy and dose attenuation of a wooden immobilization system for lung stereotactic body radiotherapy

BackgroundWe evaluated the setup error and dose absorption of an immobilization system with a shell and wooden baseplate (SW) for lung stereotactic body radiotherapy (SBRT).Materials and methodsSetup errors in 109 patients immobilized with an SW or BodyFix system (BF) were compared. Dose attenuation rates of materials for baseplates were measured with an ion-chamber. Ionization measurements were performed from 90° to 180° gantry angle in 10° increments, with the ball water equivalent phantom placed at the center of the wood and carbon baseplates whose effects on dose distribution were compared using an electron portal imaging device.ResultsThe ratio for the anterior-posterior, cranial-caudal, and right-left of the cases within 3-mm registered shifts in interfractional setup error were 90.9%, 89.2%, and 97.4% for the SW, and 93.2%, 91.6%, and 98.0% for the BF, respectively. For intrafractional setup error, 98.3%, 97.4%, and 99.1% for the SW and 96.6%, 95.8%, and 98.7% for the BF were within 3-mm registered shifts, respectively. In the center position, the average (minimum/maximum) dose attenuation rates from 90° to 180° for the wooden and carbon baseplates were 0.5 (0.1/2.8)% and 1.0 (–0.1/10.1)% with 6 MV, respectively. The gamma passing rates of 2%/2 mm for the wooden and carbon baseplates were 99.7% and 98.3% (p < 0.01).ConclusionsThe immobilization system with an SW is effective for lung SBRT since it is comparable to the BF in setup accuracy. Moreover, the wooden baseplate had lower radiation attenuation rates and affected the dose distribution less than the carbon baseplate.     

Incorrect dosimetric leaf separation in IMRT and VMAT treatment planning: Clinical impact and correlation with pretreatment quality assurance

PurposeDynamic treatment planning algorithms use a dosimetric leaf separation (DLS) parameter to model the multi-leaf collimator (MLC) characteristics. Here, we quantify the dosimetric impact of an incorrect DLS parameter and investigate whether common pretreatment quality assurance (QA) methods can detect this effect.Methods16 treatment plans with intensity modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) technique for multiple treatment sites were calculated with a correct and incorrect setting of the DLS, corresponding to a MLC gap difference of 0.5 mm. Pretreatment verification QA was performed with a bi-planar diode array phantom and the electronic portal imaging device (EPID). Measurements were compared to the correct and incorrect planned doses using gamma evaluation with both global (G) and local (L) normalization. Correlation, specificity and sensitivity between the dose volume histogram (DVH) points for the planning target volume (PTV) and the gamma passing rates were calculated.ResultsThe change in PTV and organs at risk DVH parameters were 0.4–4.1%. Good correlation (>0.83) between the PTV_mean dose deviation and measured gamma passing rates was observed. Optimal gamma settings with 3%L/3 mm (per beam and composite plan) and 3%G/2 mm (composite plan) for the diode array phantom and 2%G/2 mm (composite plan) for the EPID system were found. Global normalization and per beam ROC analysis of the diode array phantom showed an area under the curve <0.6.ConclusionsA DLS error can worsen pretreatment QA using gamma analysis with reasonable credibility for the composite plan. A low detectability was demonstrated for a 3%G/3 mm per beam gamma setting.     

Stereotactic radiotherapy for spinal hemangioblastoma – disease control and volume analysis in long-term follow up

BackgroundThis retrospective analysis evaluated the long-term outcome of spinal stereotactic body radiotherapy (SBRT) treatment for hemangioblastomas.Materials and methodsBetween 2010 and 2018, 5 patients with 18 Von-Hippel Lindau-related pial-based spinal hemangioblastomas were treated with fractionated SBRT. After precisely registering images of all relevant datasets, we delineated the gross tumor volume, spinal cord (including intramedullary cysts and/or syrinxes), and past radiotherapy regions. A sequential optimization algorithm was used for dose determinations, and patients received 25–26 Gy in five fractions or 24 Gy in three fractions. On-line image guidance, based on spinal bone structures, and two orthogonal radiographs were provided. The actuarial nidus control, surgery-free survival, cyst/syrinx changes, and progression-free survival were calculated with the Kaplan-Meier method. Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0.ResultsThe median follow-up was 5 years after SBRT. Patients displayed one nidus progression, one need of neurosurgery, and two cyst/syrinx progressions directly connected to symptom worsening. No SBRT-related complications or acute adverse radiation-related events occurred. However, one asymptomatic radiological sign of myelopathy occurred two years after SBRT. All tumors regressed; the one-year equivalent tumor volume reduction was 0.2 mL and the median volume significantly decreased by 28% (p = 0.012). Tumor volume reductions were not correlated with the mean (p = 0.19) or maximum (p = 0.16) dose.ConclusionsSBRT for pial-based spinal hemangioblastomas was an effective, safe, viable alternative to neurosurgery in asymptomatic patients. Escalating doses above the conventional dose-volume limits of spinal cord tolerance showed no additional benefit.     

Dose measurements in a thorax phantom at 3DCRT breast radiation therapy

BackgroundThe anthropomorphic and anthropometric phantom developed by the research group NRI (Núcleo de Radiações Ionizantes) can reproduce the effects of the interactions of radiation occurring in the human body. The whole internal radiation transport phenomena can be depicted by film dosimeters in breast RT. Our goal was to provide a dosimetric comparison of a radiation therapy (RT) plan in a 4MV 3D-conformal RT (4MV-3DCR T) and experimental data measured in a breast phantom.Materials and methodsThe RT modality was two parallel opposing fields for the left breast with a prescribed dose of 2.0 Gy in 25 fractions. The therapy planning system (TPS) was performed on CA T3D software. The dose readings at points of interest (POI) pre-established in TPS were recorded. An anthropometric thorax-phantom with removal breast was used. EBT2 radiochromic films were inserted into the ipisilateral breast, contralateral breast, lungs, heart and skin. The irradiation was carried out on 4/80 Varian linear accelerator at 4MV.ResultsThe mean dose at the OAR’s presented statistically significant differences (p < 0.001) of 34.24%, 37.96% and 63.47% for ipsilateral lung, contralateral lung, and heart, respectively. The films placed at the skin-surface interface in the ipsilateral breast also showed statistically significant differences (p < 0.001) of 16.43%, −10.16%, −14.79% and 15.67% in the four quadrants, respectively. In contrast, the PTV dosimeters, representative of the left breast volume, encompassed by the electronic equilibrium, presented a non-significant difference with TPS, p = 0.20 and p = 0.90.ConclusionThere was a non-significant difference of doses in PTV with electronic equilibrium; although no match is achieved outside electronic equilibrium.     

Dosimetric comparison of dynamic conformal arc integrated with segment shape optimization and variable dose rate versus volumetric modulated arc therapy for liver SBRT

AimThe aim is a dosimetric comparison of dynamic conformal arc integrated with the segment shape optimization and variable dose rate (DCA_SSO_VDR) versus VMAT for liver SBRT and interaction of various treatment plan quality indices with PTV and degree of modulation (DoM) for both techniques.BackgroundThe DCA is the state-of-the-art technique but overall inferior to VMAT, and the DCA_SSO_VDR technique was not studied for liver SBRT.Materials and methodsTwenty-five patients of liver SBRT treated using the VMAT technique were selected. DCA_SSO_VDR treatment plans were also generated for all patients in Monaco TPS using the same objective constraint template and treatment planning parameters as used for the VMAT technique. For comparison purpose, organs at risk (OARs) doses and treatment plans quality indices, such as maximum dose of PTV (D_max%), mean dose of PTV (D_mean%), maximum dose at 2 cm in any direction from the PTV (D_2cm%), total monitor units (MU’s), gradient index R_50%, degree of modulation (DoM), conformity index (CI), homogeneity index (HI), and healthy tissue mean dose (HTMD) were compared.ResultsSignificant dosimetric differences were observed in several OARs doses and lowered in VMAT plans. The D_2cm%, R_50%, CI, HI and HTMD are dosimetrically inferior in DCA_SSO_VDR plans. The higher DoM results in poor dose gradient and better dose gradient for DCA_SSO_VDR and VMAT treatment plans, respectively.ConclusionsFor liver SBRT, DCA_SSO_VDR treatment plans are neither dosimetrically superior nor better alternative to the VMAT delivery technique. A reduction of 69.75% MU was observed in DCA_SSO_VDR treatment plans. For the large size of PTV and high DoM, DCA_SSO_VDR treatment plans result in poorer quality.