GTV Volume Research Articles

Fraction Size, Total Dose and Respiratory Control Impact Local Control in Adrenal SBRT

Stereotactic body radiotherapy (SBRT) is an effective treatment for oligometastatic disease in multiple sites, however, the optimal radiation dose for long term local control of adrenal metastases has not yet been determined. The aim of this study is to evaluate outcomes of adrenal SBRT and to evaluate factors that correlate with local control MATERIALS/METHODS: After IRB approval, a retrospective data review of patients treated with SBRT on adrenal metastases was conducted, at a medical center in Israel between 2015 and 2021. Biologic Equivalent Dose (BED) were calculated using an alpha beta ration of 10. Kaplan Meier and Cox regression were calculated to describe the hazard ratio for local control and survival using statistical software. Fifty-eight cases of adrenal SBRT were identified. The average age was 67 years (ranging 42-92). Forty-three percent of primary tumor was non-small cell lung cancer. The lesions were equally distributed between the right and left adrenal gland. Six patients had bilateral radiation treatment. Fifty-eight percent of the cases were in the setting of oligometastatic disease (less than 5 lesions) with the rest having progression in the adrenal. PET-CT scans were available for follow up in 55% of patients and CT in the rest. The average GTV volume was 42 cm2 respiratory control through 4D and breath hold was performed in 86% of cases. The median follow up time, for local control, was 10 months with a range of 1-54 mos. Univariate analysis local control, during the last follow up, was seen in 74% of cases. Total dosage was equal to or above 72 Gy and dosage per fraction was equal to or above 8 Gy. The use of respiratory motion was found significant for local control. Only a fraction size equal to or above 8 Gy and a total dosage equal to and above 72 Gy were found significant for local failure (HR = 0.26, p = 0.024 and HR = 0.28, p = 0.019). With multivariable analysis the dosage per fraction ≥8 Gy continued to be significant after adjusting for total dose, histology, side, and motion management. Two patients had clinical signs of adrenal insufficiency and both received bilateral adrenal radiation. Bowel toxicity was low: 1 patient had >G3 toxicity. In the largest single institution series reported to date, we found unilateral adrenal SBRT to be safe, however, bilateral treatment harbors a risk of adrenal insufficiency. Dose per fraction ≥8 Gy was the most powerful predictor of local control, and a total dose ≥72gy and motion management were also significant. In conclusion, we propose a treatment regimen with a fraction size of at least 8 Gy and a total dosage of at least 72 Gy for evaluation, in a prospective clinical trial.

Automatic Prediction of Metastasis-Free Survival (MFS) Using Prostate-Specific Membrane Antigen (PSMA) PET for Oligometastatic Castration-Sensitive Prostate Cancer (omCSPC)

Recent data have shown the promise of metastasis-directed therapy (MDT) to improve outcomes in omCSPC patients. Response biomarkers are still needed to identify patients at an early time point who will not respond to the treatment. We have shown that PSMA PET-CT SUVmax changes over time may be a useful response biomarker that correlates with MFS, an important endpoint in these omCSPC patients. This study investigated radiomic imaging biomarkers derived from PSMA-PET acquired pre- and post-MDT for MFS prediction, which may provide better features to discriminate response in the future to improve the outcome of these patients. We accrued an international multi-institutional cohort of omCSPC patients treated with stereotactic ablative radiation therapy (SABR) MDT. The cohort includes 32 patients from Institution 1 (USA) and 38 patients from Institution 2 (Europe). Both pre- and 6-month post-treatment PSMA-PET/CT were acquired. Combat was used for data harmonization in the image domain to minimize imaging variations across institutions. We defined the GTV volume as zone 1 and a 3-5 mm expansion ring area outside the GTV as zone 2 for radiomics analysis. 874 radiomics features (214 original and 660 wavelet filtered features) were extracted from both zones using open-source software and used together for MFS prediction. Function Chi2 was used to select the most significant five features. Several machine learning models (Random Forest, Logistic regression, Support Vector Machine, Naïve Bayesian) were implemented to predict MFS. The models were tested using both a leave-one-out strategy and cross-validation across the two institutions. In the leave-one-out biomarker using 70 patients, random forest achieved the best accuracy, with MFS predicted correctly for 56 (80% of 70) patients. The five radiomic features identified based on their ability to predict MFS included Entropy, Skewness, and Compactness from zone 1, Skewness, and Mesh volume from zone 2. In the cross-institution tests, random forest predicted MFS correctly for 24 (75% of 32) patients when being trained using 38 Institution 2 patients and validated against 32 Institution 1 patients. Vice versa, the model predicted MFS correctly for 28 (74% of 38) patients when being trained using Institution 1 patients and validation using Institution 2 patients. The five features identified for prediction included Entropy and Skewness from both zones and Flatness from zone 1. Our study demonstrated the promise of using pre- and post-MDT PSMA-PET-based imaging radiomic biomarkers for MFS prediction for omCSPC patients. Imaging biomarkers predictive of MFS were identified in both GTV and the ring area outside GTV. Over 74% prediction accuracy was achieved in the cross-institution validation test. The model provides a valuable tool for prognosis prediction early following MDT, which opens up a unique opportunity for monitoring or treatment interventions for patients identified with poor prognoses to improve outcomes.

Dosimetric Impact of Setup Errors in Single-Isocenter VMAT Radiosurgery for Brain Metastases

In stereotactic radiosurgery (SRS) and fractionated stereotactic radiosurgery (fSRS) of brain metastases (BM) using single-isocenter VMAT, intra-fraction positioning errors may affect target coverage. This study aims to investigate geometric and dosimetric accuracy in single and multiple BM treatments. Seventy patients with single (n = 38) and multiple (n = 32) BM treated with 15-21 Gy in 1 (n = 59) or 27 Gy in 3 (n = 11) fractions using coplanar FFF-VMAT technique were analyzed. PTV was defined by a 2 mm isotropic GTV expansion. Pre-treatment setup errors were evaluated with CBCT and corrected with a robotic six degrees-of-freedom couch. For each fraction, intra-fractional errors were measured by post-treatment CBCT and applied to the planning CT. Plans involving translations and rotations (Fx-plan) were recalculated with Monte Carlo TPS. Original and Fx-plans were compared in terms of target and brain dose parameters, performing the Wilcoxon-Mann-Whitney test (alpha = 0.05). The relationships of the BM volume, maximum dimension, distance-to-isocenter (for multiple BM cases only) and barycenter shift with the difference in target coverage between the two plans were investigated. The median post-treatment 3D error and maximum rotational error over all 129 BM were 0.5 mm [0.1-2.7] and 0.3° [0.0-1.3], respectively. The resulting median BM barycenter shift was 0.5 mm [0.1-2.7]. The percentage of fractions in which at least one BM barycenter shifted by more than 2 mm from the planned position was 4% and 1% for single and multiple BM cases, respectively. The median single GTV volume was 0.27 cc [0.01-10.48], while the PTV had a median volume of 1.05 cc [0.12-17.05]. The median BM maximum dimension was 10.7 mm [2.9-34.1] and for multiple BM the median distance-to-isocenter was 5.15 cm [0.89-7.52]. For single BM patients, the GTV D95% was never reduced by > 5%, while PTV D95% reductions > 1% occurred in only 11 (29%) PTV. For multiple BM patients, the target statistics were slightly worse, with dose deficits larger than 5% and 1% occurring respectively in 2 BM and 34 (37%) PTV. Anyway, the majority of single and multiple BM had a loss of coverage for both GTV and PTV below 1% in Fx-plans. Larger than 5% brain V12 Gy (SRS) and V20 Gy (fSRS) increases were observed for only one single BM patient. None of the two dosimetric comparisons resulted statistically significant (p>0.05). The differences in target coverage showed a moderate-to-strong correlation only with the BM barycenter shift in both cases (R2 = 0.70-0.73 for single and R2 = 0.44-0.50 for multiple BM). Due to the optimal patient setup, as well as the full six degrees-of-freedom corrections, the safety PTV margin, and the fast beam delivery, the dosimetric effects of residual setup and patient motion errors for both single and multiple BM cases were negligible. These findings warrant a potential reduction in the PTV margin with this treatment technique.

Impact of magnetic resonance imaging-related geometric distortion of dose distribution in fractionated stereotactic radiotherapy in patients with brain metastases.

The geometric distortion related to magnetic resonance (MR) imaging in adiagnostic radiology (MRDR) and radiotherapy (MRRT) setup is evaluated, and the dosimetric impact of MR distortion on fractionated stereotactic radiotherapy (FSRT) in patients with brain metastases is simulated. An anthropomorphic skull phantom was scanned using a1.5‑T MR scanner, and the magnitude of MR distortion was calculated with (MRDR-DC and MRRT-DC) and without (MRDR-nDC and MRRT-nDC) distortion-correction algorithms. Automated noncoplanar volumetric modulated arc therapy (HyperArc, HA; Varian Medical Systems, Palo Alto, CA, USA) plans were generated for 53patients with 186 brain metastases. The MR distortion at each gross tumor volume (GTV) was calculated using the distance between the center of the GTV and the MR image isocenter (MIC) and the quadratic regression curve derived from the phantom study (MRRT-DC and MRRT-nDC). Subsequently, the radiation isocenter of the HA plans was shifted according to the MR distortion at each GTV (HADC and HAnDC). The median MR distortions were approximately 0.1 mm when the distance from the MIC was < 30 mm, whereas the median distortion varied widely when the distance was > 60 mm (0.23, 0.47, 0.37, and 0.57 mm in MRDR-DC, MRDR-nDC, MRRT-DC, and MRRT-nDC, respectively). The dose to the 98% of the GTV volume (D98%) decreased as the distance from the MIC increased. In the HADC plans, the relative dose difference of D98% was less than 5% when the GTV was located within 70 mm from the MIC, whereas the underdose of GTV exceeded 5% when it was 48 mm (-26.5% at maximum) away from the MIC in the HAnDC plans. Use of adistortion-correction algorithm in the studied MR diagnoses is essential, and the dosimetric impact of MR distortion is not negligible, particularly for tumors located far away from the MIC.

PREDICTORS OF TUMOR DYNAMICS DURING A COURSE OF 30-FRACTION RADIOTHERAPY FOR GLIOBLASTOMA

Abstract We aim to identify predictors of tumor dynamics during radiotherapy for glioblastoma. METHODS: This is a prospective serial MRI study in patients with glioblastoma. MRIs were obtained at radiotherapy planning (F0), fraction-10 (F10), and fraction-20 (F20). The tumor dynamics metrics (relative to F0) assessed included: relative gross tumor volume (GTV) changes (Vrel) and migration distance (dM). RESULTS: 129 patients were included in this study. Median GTV was 20.9cc at F0, 17.6cc at F10 (Vrel 0.85), and 16.1cc at F20 (Vrel 0.78). Patients with no corpus-callosum involvement (CCI) (vs with CCI) had more marked GTV volume reduction: Vrel 0.82 vs 1.02 at F10 (P=0.05), and Vrel 0.77 vs 0.88 at F20 (P=0.03). Patients with gross total resection (GTR) had more marked GTV volume reduction (vs subtotal resection (STR) vs biopsy (Bx)): Vrel 0.78, 0.85 and 1.07 at F10 (P=0.001), and Vrel 0.69, 0.80, 1.04 at F20 (P=0.001). The median dM were 4.7mm at both F10 and F20. Patients with CCI had larger dM (vs no CCI): 41% vs 12% had dM&amp;gt;10mm at F10 (P=0.01), and 45% vs 9% had dM&amp;gt;10mm at F20 (P&amp;lt;0.001). At F20, 0%, 25% and 19% of patients with GTR, STR and Bx had dM&amp;gt;10mm (P=0.002). Age, sex, MGMT methylation and IDH-mutation status were not associated with tumor dynamics during treatment. CONCLUSION: CCI and extent of surgery predict for tumor dynamics, which may allow us to better select patients who benefit the most from re-planning/ treatment adaptation during radiotherapy.

Dosimetric analysis of stereotactic radiosurgery planning techniques in different treatment devices in trigeminal nerve irradiation

This study aims to search for a cheaper and easily accessible alternative to Cyberknife, which is frequently used as a stereotactic radiosurgery device in the treatment of trigeminal neuralgia.Using tomography images of 20 trigeminal neuralgia patients treated with CyberKnife treatment devices, stereotactic planning techniques were applied retrospectively to the same patients on Tomotherapy and Versa HD treatment devices. Each patient was planned to receive a dose of 60 Gy in a single fraction.Treatment plans were evaluated in terms of the minimum, mean, and maximum doses received by the GTV in all three devices, as well as the percentage of the GTV volume that could receive 60 Gy. D98%, D90%, D50%, D30%, D10%, and conformity index (CI) and homogeneity index (HI) were also evaluated for GTV. The maximum doses of brainstem, D1%, D2%, D5%, and D10% were evaluated. Other critical organs: optic chiasm, optic nerves, cochlea's, eyes, and lenses were evaluated for their maximum dose. In addition, the volumes of 50% and 20% isodoses in healthy tissue were compared.While the Cyberknife device is superior in terms of brain stem doses, Versa HD device stands out in terms of maximum doses of optical structures.

Interobserver Variability in Contouring Hepatocellular Carcinoma at a Tertiary Center.

The optimal imaging test for delineation of the gross tumor volume (GTV) in hepatocellular carcinoma has not been defined. The hypothesis is that magnetic resonance imaging (MRI) allows for better visualization of the extent of tumor and will optimize the accuracy of tumor delineation for liver stereotactic radiotherapy compared with computed tomography (CT) only. We evaluated the interobserver agreement in GTV of hepatocellular carcinoma in a multicenter panel and compared MRI and CT in GTV delineation. After the institutional review boards approved the study, we analyzed anonymous CT and MRI obtained from five patients with hepatocellular carcinoma. Eight radiation oncologists at our center used CT and MRI to delineate five GTVs of liver tumors. In both CT and MRI, the GTV volumes were compared. The median GTV volume on MRI was 2.4 cm3 (range=0.59-15.6 cm3) compared to 3.5 cm3 (range=0.52-24.9 cm3) on CT (p=0.36). The GTV volume as defined on MRI was larger or at least as large as the GTV volume on CT in two cases. Variance and standard deviation between observers in CT and MRI were minor (6 vs. 7.87 cm3, and 2.5 vs. 2.8 cm3 respectively). In cases with well-defined tumors, CT is easier and reproducible. In cases with no defined tumor in CT, other tools are needed and MRI can be complementary. The interobserver variability in target delineation of hepatocellular carcinoma in this study is noteworthy.

Deep learning based automated delineation of the intraprostatic gross tumour volume in PSMA-PET for patients with primary prostate cancer

PurposeWith the increased use of focal radiation dose escalation for primary prostate cancer (PCa), accurate delineation of gross tumor volume (GTV) in prostate-specific membrane antigen PET (PSMA-PET) becomes crucial. Manual approaches are time-consuming and observer dependent. The purpose of this study was to create a deep learning model for the accurate delineation of the intraprostatic GTV in PSMA-PET. MethodsA 3D U-Net was trained on 128 different 18F-PSMA-1007 PET images from three different institutions. Testing was done on 52 patients including one independent internal cohort (Freiburg: n = 19) and three independent external cohorts (Dresden: n = 14 18F-PSMA-1007, Boston: Massachusetts General Hospital (MGH): n = 9 18F-DCFPyL-PSMA and Dana-Farber Cancer Institute (DFCI): n = 10 68Ga-PSMA-11). Expert contours were generated in consensus using a validated technique. CNN predictions were compared to expert contours using Dice similarity coefficient (DSC). Co-registered whole-mount histology was used for the internal testing cohort to assess sensitivity/specificity. ResultsMedian DSCs were Freiburg: 0.82 (IQR: 0.73–0.88), Dresden: 0.71 (IQR: 0.53–0.75), MGH: 0.80 (IQR: 0.64–0.83) and DFCI: 0.80 (IQR: 0.67–0.84), respectively. Median sensitivity for CNN and expert contours were 0.88 (IQR: 0.68–0.97) and 0.85 (IQR: 0.75–0.88) (p = 0.40), respectively. GTV volumes did not differ significantly (p > 0.1 for all comparisons). Median specificity of 0.83 (IQR: 0.57–0.97) and 0.88 (IQR: 0.69–0.98) were observed for CNN and expert contours (p = 0.014), respectively. CNN prediction took 3.81 seconds on average per patient. ConclusionThe CNN was trained and tested on internal and external datasets as well as histopathology reference, achieving a fast GTV segmentation for three PSMA-PET tracers with high diagnostic accuracy comparable to manual experts.

Automated tracking of morphologic changes in weekly magnetic resonance imaging during head and neck radiotherapy.

Anatomic changes during head and neck radiotherapy can impact dose delivery, necessitate adaptive replanning, and indicate patient-specific response to treatment. We have developed an automated system to track these changes through longitudinal MRI scans to aid identification and clinical intervention. The purpose of this article is to describe this tracking system and present results from an initial cohort of patients. The Automated Watchdog in Adaptive Radiotherapy Environment (AWARE) was developed to process longitudinal MRI data for radiotherapy patients. AWARE automatically identifies and collects weekly scans, propagates radiotherapy planning structures, computes structure changes over time, and reports important trends to the clinical team. AWARE also incorporates manual structure review and revision from clinical experts and dynamically updates tracking statistics when necessary. AWARE was applied to patients receiving weekly T2-weighted MRI scans during head and neck radiotherapy. Changes in nodal gross tumor volume (GTV) and parotid gland delineations were tracked over time to assess changes during treatment and identify early indicators of treatment response. N=91 patients were tracked and analyzed in this study. Nodal GTVs and parotids both shrunk considerably throughout treatment (-9.7±7.7% and -3.7±3.3% per week, respectively). Ipsilateral parotids shrunk significantly faster than contralateral (-4.3±3.1%vs. -2.9±3.3% per week, p=0.005) and increased in distance from GTVs over time (+2.7±7.2% per week, p<1×10-5 ). Automatic structure propagations agreed well with manual revisions (Dice=0.88±0.09 for parotids and 0.80±0.15 for GTVs), but for GTVs the agreement degraded 4-5weeks after the start of treatment. Changes in GTV volume observed by AWARE as early as one week into treatment were predictive of large changes later in the course (AUC=0.79). AWARE automatically identified longitudinal changes in GTV and parotid volumes during radiotherapy. Results suggest that this system may be useful for identifying rapidly responding patients as early as one week into treatment.

Efficacy and safety of CT-guided 125I seed implantation by coplanar template as a salvage therapy for vertebral metastases after failure of external beam radiation therapy: a retrospective study.

To evaluate the efficacy safety of computed tomography (CT)-guided 125I seed implantation by coplanar template for vertebral metastases after failure of external beam radiation therapy (EBRT). Retrospective analysis of the clinical outcomes of 58 patients with vertebral metastases after failure of EBRT, who underwent 125I seed implantation as a salvage treatment with a CT-guided coplanar template-assisted technique from January 2015 to January 2017. The mean post-operative NRS score decreased significantly at T4w (3.5 ± 0.9, p<0.01), T8w (2.1 ± 0.9, p<0.01), T12w (1.5 ± 0.7, p< 0.01) and T6m (1.2 ± 0.6, p< 0.01) respectively. The local control rates after 3, 6, 9 and 12 months were 100% (58/58), 93.1% (54/58), 87.9% (51/58), and 81% (47/58), respectively. The median overall survival time was 18.52months (95% CI, 16.24-20.8), and 1- and 2-year survival rates were 81% (47/58) and 34.5% (20/58), respectively. By performing a paired t-test analysis, there was no significant difference in D90, V90, D100, V100, V150, V200, GTV volume, CI, EI and HI between preoperative and postoperative (p>0.05). 125I seed implantation can be used as a salvage treatment for patients with vertebral metastases after failure of EBRT.

Integrating CT-based radiomic model with clinical features improves long-term prognostication in high-risk prostate cancer.

High-risk prostate cancer (PCa) is often treated by prostate-only radiotherapy (PORT) owing to its favourable toxicity profile compared to whole-pelvic radiotherapy. Unfortunately, more than 50% patients still developed disease progression following PORT. Conventional clinical factors may be unable to identify at-risk subgroups in the era of precision medicine. In this study, we aimed to investigate the prognostic value of pre-treatment planning computed tomography (pCT)-based radiomic features and clinical attributes to predict 5-year progression-free survival (PFS) in high-risk PCa patients following PORT. A total of 176 biopsy-confirmed PCa patients who were treated at the Hong Kong Princess Margaret Hospital were retrospectively screened for eligibility. Clinical data and pCT of one hundred eligible high-risk PCa patients were analysed. Radiomic features were extracted from the gross-tumour-volume (GTV) with and without applying Laplacian-of-Gaussian (LoG) filter. The entire patient cohort was temporally stratified into a training and an independent validation cohort in a ratio of 3:1. Radiomics (R), clinical (C) and radiomic-clinical (RC) combined models were developed by Ridge regression through 5-fold cross-validation with 100 iterations on the training cohort. A model score was calculated for each model based on the included features. Model classification performance on 5-year PFS was evaluated in the independent validation cohort by average area-under-curve (AUC) of receiver-operating-characteristics (ROC) curve and precision-recall curve (PRC). Delong's test was used for model comparison. The RC combined model which contains 6 predictive features (tumour flatness, root-mean-square on fine LoG-filtered image, prostate-specific antigen serum concentration, Gleason score, Roach score and GTV volume) was the best-performing model (AUC = 0.797, 95%CI = 0.768-0.826), which significantly outperformed the R-model (AUC = 0.795, 95%CI = 0.774-0.816) and C-model (AUC = 0.625, 95%CI = 0.585-0.665) in the independent validation cohort. Besides, only the RC model score significantly classified patients in both cohorts into progression and progression-free groups regarding their 5-year PFS (p< 0.05). Combining pCT-based radiomic and clinical attributes provided superior prognostication value regarding 5-year PFS in high-risk PCa patients following PORT. A large multi-centre study will potentially aid clinicians in implementing personalised treatment for this vulnerable subgroup in the future.

Comparison of the Incidence Rate of Radiation Pneumonitis Observed in Patients with Advanced Lung Adenocarcinoma Treated with Simultaneous Thoracic Radiotherapy and 1G/2G/3G EGFR-TKIs.

The present study aimed to evaluate the incidence rate of radiation pneumonitis (RP) in patients with advanced lung adenocarcinoma treated with first-generation (1G), second-generation (2G), or third-generation (3G) epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) combined with thoracic radiotherapy (TRT). Patients with advanced lung adenocarcinoma simultaneously treated with 1G/2G/3G EGFR-TKIs and TRT between 2015-2021 at Shandong Cancer Hospital and Institute were screened. The incidence rate of clinical and imaging RP was compared between the three groups. A total of 200 patients treated with EGFR-TKIs were enrolled in this study, including 100 patients who were treated with 1G EGFR-TKIs, 50 patients who were treated with 2G EGFR-TKIs, and 50 patients who were treated with 3G EGFR-TKIs (patients matched in a 2:1:1 ratio for tumor characteristics). The overall incidence of clinical RP in the 1G, 2G, and 3G EGFR-TKI groups were 29%, 48%, and 28% (p=0.043), respectively, and that of imaging RP were 33%, 58%, and 36% (p=0.010), respectively. The incidence of RP with a clinical grade ≥3 in the three groups were 14%, 28%, and 12% (p=0.055), respectively, and that with an imaging grade ≥3 in the three groups were 11%, 32%, and 10% (p=0.002), respectively. The incidence of clinical RP was higher in the CFRT group than in the SBRT group, with an overall clinical grade of 38% vs 10% (p<0.001) and imaging grade of 46% vs 10% (p<0.001), respectively. In the multivariate analysis, only GTV volume was an independent predictive factor for all risks of clinical and imaging RP. V20 and grouping of 1G/2G/3G EGFR-TKIs were other independent predictive factors for the risk factors of RP for imaging grades. Compared with 2G EGFR-TKIs combined with TRT, 1G or 3G EGFR-TKIs combined with TRT achieved a lower incidence of RP.

Role of palliative SBRT in barcelona clinic liver cancer-stageC hepatocellular carcinoma patients.

To evaluate the role of palliative stereotactic body radiation therapy (SBRT) in Barcelona Clinic Liver Cancer stage‑C (BCLC-C) hepatocellular carcinoma (HCC) patients who are not suitable for other loco-regional therapies. It is an observational retrospective study done between May 2020 and September 2021. The data were collected from 35patients of advanced HCC who underwent SBRT. Patients of Child Pugh status (CPs) A5-B7 and with aliver reserve of ≥ 700cc were included. Local control (LC), overall survival (OS) and adverse events including decompensation were carefully recorded. In the cohort, Portal vein and IVC tumor thrombosis were present in 33(94.3%) and 8(22.85%) patients, respectively. Lung and nodal metastasis were found in 11(31.4%) and 21(60%) of patients, respectively. The median gross tumor volume (GTV) was 563cc (range 80-1925cc). The median SBRT dose prescription was 35 Gy (range 25-40 Gy) in 5-10 fractions. Post radiation therapy, there was improvement in pain and discomfort in24 out of29 (82.75%) and18 out of23 (78%) patients respectively. Also bone metastasis related pain was improved in all3 (100%) patients. One year LC, and OS were 80% and 30% respectively. On multivariate analysis, the GTV volume > 750cc and PIVKA-II > 8000 mAU/ml remained the predictor factor for poor OS. Post SBRT, change in child-pugh score by 1point was observed in 7patients (20%) which was managed conservatively. SBRT is asafe and feasible option for BCLC‑C HCC. It not only improves the quality of life by symptom control but also results in good LC and OS with acceptable toxicity. SBRT should be considered in amultidisciplinary fashion for patients presenting with advanced HCCs.

Combined biology-guided radiotherapy and Lutetium PSMA theranostics treatment in metastatic castrate-resistant prostate cancer.

Lutetium-177 [177Lu]-PSMA-617 is a targeted radioligand that binds to prostate-specific membrane antigen (PSMA) and delivers radiation to metastatic prostate cancer. The presence of PSMA-negative/FDG-positive metastases can preclude patients from being eligible for this treatment. Biology-guided radiotherapy (BgRT) is a treatment modality that utilises tumour PET emissions to guide external beam radiotherapy. The feasibility of combining BgRT and Lutetium-177 [177Lu]-PSMA-617 for patients with PSMA-negative/FDG-positive metastatic prostate cancer was explored. All patients excluded from the LuPSMA clinical trial (ID: ANZCTR12615000912583) due to PSMA/FDG discordance were retrospectively reviewed. A hypothetical workflow where PSMA-negative/FDG-positive metastases would be treated with BgRT whilst PSMA-positive metastases would be treated with Lutetium-177 [177Lu]-PSMA-617 was considered. Gross tumour volume (GTV) of PSMA-negative/FDG-positive tumours were delineated on the CT component of the FDG PET/CT scan. Tumours were deemed suitable for BgRT if (1) normalised SUV (nSUV), defined as the ratio of maximum SUV (SUVmax) inside the GTV to mean SUV inside a 5 mm/10 mm/20mm margin expansion of the GTV, was larger than a pre-specified nSUV threshold and (2) there was no PET avidity inside the margin expansion. In 75 patients screened for Lutetium-177 [177Lu]-PSMA-617 treatment, 6 patients were excluded due to PSMA/FDG discordance and 89 PSMA-negative/FDG-positive targets were identified. GTV volumes ranged from 0.3 cm3 to 186 cm3 (median GTV volume = 4.3 cm3, IQR = 2.2 cm3 - 7.4 cm3). SUVmax inside GTVs ranged between 3 and 12 (median SUVmax = 4.8, IQR = 3.9 - 6.2). With nSUV ≥ 3, 67%/54%/39% of all GTVs were suitable for BgRT within 5 mm/10 mm/20mm from the tumour. Bone and lung metastases were the best candidates for BgRT (40%/27% of all tumours suitable for BgRT with nSUV ≥ 3 within 5mm from the GTV were bone/lung GTVs). Combined BgRT/Lutetium-177 [177Lu]-PSMA-617 therapy is feasible for patients with PSMA/FDG discordant metastases.

Why subclinical involvement is prescribed the same high dose as gross tumor volume: A study on high-dose clinical target volume in intensity-modulated radiotherapy plan of nasopharyngeal carcinoma.

Most nasopharyngeal carcinoma (NPC) protocols define primary gross tumor volume (GTVnx) plus a range from 2 to 5 mm as the high-dose clinical target volume (hd-CTV). However, in China, hd-CTV is defined as GTVnx plus 0 mm. A total of 40 patients with newly diagnosed nonmetastatic NPC (T1-T4 ten cases each) treated with IMRT were consecutively enrolled. Real and virtual treatment plans were designed according to the definitions of hd-CTV recommended by China and Radiation Therapy Oncology Group (RTOG), respectively. The hd-CTV in China was significantly smaller than that of RTOG. Exposure doses to 5 mm subclinical involvement and OARs as well as NTCP in the China treatment plan were significantly lower than those of RTOG. It could be recommended to divide the hd-CTV into GTV and subclinical target volume and to prescribe different doses for the GTV and subclinical involvement in the IMRT plan of NPC.

Identifying predictors of on-table adaptation for pancreas stereotactic body radiotherapy (SBRT)

PurposeTo identify any clinical or dosimetric parameters that predict which individuals may benefit from on-table adaptation during pancreas stereotactic body radiotherapy (SBRT) with MRI-guided radiotherapy. Methods and materialsThis was a retrospective study of patients undergoing MRI-guided SBRTfrom 2016 to 2022.Pre-treatment clinical variables and dosimetric parameters on the patient’s simulation scan were recorded for each SBRT course, and their ability to predict for on-table adaptation was analyzed using ordinal logistic regression. The outcome measure was number of fractions adapted. ResultsSixty-three SBRT courses consisting of 315 fractions were analyzed. Median prescription dose was 40 Gy in five fractions (range, 33–50 Gy); 52% and 48% of courses were prescribed ≤40 Gy and >40 Gy, respectively. The median minimum dose delivered to 95% (D95) of the gross tumor volume (GTV) and planning target volume (PTV) was 40.1 Gy and 37.0 Gy, respectively. Median number of fractions adapted per course was three, with 58% (183 out of 315) total fractions adapted. On univariable analysis, the prescription dose (>40 Gy vs ≤40 Gy), GTV volume, stomach V20 and V25, duodenum V20 and dose maximum, large bowel V33 and V35, GTV dose minimum, PTV dose minimum, and gradient index were significant determinants foradaptation (all p < 0.05). On multivariable analysis, only the prescription dose was significant (adjusted odds ratio 19.7, p = 0.005), but did not remain significant after multiple test correction (p = 0.08). ConclusionsThe likelihood of needing on-table adaptation could not be reliably predicted a priori using pre-treatment clinical characteristics, dosimetry to nearby organs at risk, or other dosimetric parameters based on the patient’s anatomy at the time of simulation, suggesting the critical importance of day-to-day variations in anatomy and increasing access to adaptive technology for pancreas SBRT. A higher (ablative) prescription dose was associated with increased use of adaptation.

Use of a neural network-based prediction method to calculate the therapeutic dose in boron neutron capture therapy of patients with glioblastoma.

Boron neutron capture therapy (BNCT) is a binary radiotherapy based on the 10 B(n, α)7 Li capture reaction. Nonradioactive isotope 10 B atoms which selectively concentrated in tumor cells will react with low energy neutrons (mainly thermal neutrons) to produce secondary particles with high linear energy transfer, thus depositing dose in tumor cells. In clinical practice, an appropriate treatment plan needs to be set on the basis of the treatment planning system (TPS). Existing BNCT TPSs usually use the Monte Carlo method to determine the three-dimensional (3D) therapeutic dose distribution, which often requires a lot of calculation time due to the complexity of simulating neutron transportation. A neural network-based BNCT dose prediction method is proposed to achieve the rapid and accurate acquisition of BNCT 3D therapeutic dose distribution for patients with glioblastoma to solve the time-consuming problem of BNCT dose calculation in clinic. The clinical data of 122 patients with glioblastoma are collected. Eighteen patients are used as a test set, and the rest are used as a training set. The 3D-UNET is constructed through the design optimization of input and output data sets based on radiation field information and patient CT information to enable the prediction of 3D dose distribution of BNCT. The average mean absolute error of the predicted and simulated equivalent doses of each organ are all less than 1Gy. For the dose to 95% of the GTV volume (D95 ), the relative deviation between predicted and simulated results are all less than 2%. The average 2mm/2% gamma index is 89.67%, and the average 3mm/3% gamma index is 96.78%. The calculation takes about 6h to simulate the 3D therapeutic dose distribution of a patient with glioblastoma by Monte Carlo method using Intel Xeon E5-2699 v4, whereas the time required by the method proposed in this study is almost less than 1 s using a Titan-V graphics card. This study proposes a 3D dose prediction method based on 3D-UNET architecture in BNCT, and the feasibility of this method is demonstrated. Results indicate that the method can remarkably reduce the time required for calculation and ensure the accuracy of the predicted 3D therapeutic dose-effect. This work is expected to promote the clinical development of BNCT in the future.

Feasibility study of deep learning-based markerless real-time lung tumor tracking with orthogonal X-ray projection images.

The feasibility of a deep learning-based markerless real-time tumor tracking (RTTT) method was retrospectively studied with orthogonal kV X-ray images and clinical tracking records acquired during lung cancer treatment. Ten patients with lung cancer treated with marker-implanted RTTT were included. The prescription dose was 50Gy in four fractions, using seven- to nine-port non-coplanar static beams. This corresponds to 14-18 X-ray tube angles for an orthogonal X-ray imaging system rotating with the gantry. All patients underwent 10 respiratory phases four-dimensional computed tomography. After a data augmentation approach, for each X-ray tube angle of a patient, 2250 digitally reconstructed radiograph (DRR) images with gross tumor volume (GTV) contour labeled were obtained. These images were adopted to train the patient and X-ray tube angle-specific GTV contour prediction model. During the testing, the model trained with DRR images predicted GTV contour on X-ray projection images acquired during treatment. The predicted three-dimensional (3D) positions of the GTV were calculated based on the centroids of the contours in the orthogonal images. The 3D positions of GTV determined by the marker-implanted RTTT during the treatment were considered as the ground truth. The 3D deviations between the prediction and the ground truth were calculated to evaluate the performance of the model. The median GTV volume and motion range were 7.42 (range, 1.18-25.74) cm3 and 22 (range, 11-28) mm, respectively. In total, 8993 3D position comparisons were included. The mean calculation time was 85ms per image. The overall median value of the 3D deviation was 2.27 (interquartile range: 1.66-2.95) mm. The probability of the 3D deviation smaller than 5mm was 93.6%. The evaluation results and calculation efficiency show the proposed deep learning-based markerless RTTT method may be feasible for patients with lung cancer.

A novel approach for dose painting radiotherapy of brain metastases guided by mr perfusion images.

To investigate the feasibility and dosimetric index features of dose painting guided by perfusion heterogeneity for brain metastasis (BMs) patients. A total of 50 patients with single BMs were selected for this study. CT and MR simulation images were obtained, including contrast-enhanced T1-weighted images (T1WI+C) and cerebral blood flow (CBF) maps from 3D-arterial spin labeling (ASL). The gross tumor volume (GTV) was determined by fusion of CT and T1WI+C images. Hypoperfused subvolumes (GTVH) with less than 25% of the maximum CBF value were defined as the dose escalation region. The planning target volume (PTV) and PTVH were calculated from GTV and GTVH respectively. The PTVN was obtained by subtracting PTVH from PTV, and conventional dose was given. Three kinds of radiotherapy plans were designed based on the CBF values. Plan 1 was defined as the conventional plan with an arbitrary prescription dose of 60 Gy for PTV. For dose painting, Plan 2 and Plan 3 escalated the prescription dose for PTVH to 72 Gy based on Plan 1, but Plan 3 removed the maximum dose constraint. Dosimetric indices were compared among the three plans. The mean GTV volume was 34.5 (8.4-118.0) cm3, and mean GTVH volume was 17.0 (4.5-58.3) cm3, accounting for 49.3% of GTV. Both conventional plan and dose painting plans achieved 98% target coverage. The conformity index of PTVH were 0.44 (Plan1), 0.64 and 0.72 (Plan 2 and Plan 3, P<0.05). Compared to Plan 1, the D2%, D98% and Dmean values of the PTVH escalated by 20.50%, 19.32%, and 19.60% in Plan 2 and by 24.88%, 17.22% and 19.22% in Plan 3 respectively (P<0.05). In the three plans, the index of achievement value for PTVH was between 1.01 and 1.03 (P<0.05). The dose increment rates of Plan 2 and Plan 3 for each organs at risk (OARs) was controlled at 2.19% - 5.61% compared with Plan 1. The doses received by OARs did not significantly differ among the three plans (P >0.05). BMs are associated with significant heterogeneity, and effective escalation of the dose delivered to target subvolumes can be achieved with dose painting guided by 3D-ASL without extra doses to OARs.

Hypofractionated concurrent chemoradiotherapy related lymphopenia and its association with survival in locally advanced non-small cell lung cancer patients.

To evaluate longitudinal changes of concurrent chemoradiotherapy (CCRT) related lymphopenia and its association with survival in locally advanced non-small cell lung cancer (LA-NSCLC) patients. Total lymphocyte count (TLC) at baseline, weekly intervals during CCRT and monthly intervals up to 12 months after CCRT were documented. The Common Terminology Criteria for Adverse Events version 5.0 was used to grade the severity of lymphopenia. Cox regression analysis was performed to evaluate the association between overall survival (OS) and CCRT related lymphopenia at different timepoints. Logistic regression model was used to determine the clinical factors associated with TLC level. 381 LA-NSCLC patients treated with definitive CCRT without consolidation therapy (NCT02573506/NCT02577341) between 2011 to 2020 were analyzed. With a median follow-up of 45.8 months, the median OS was 41.0 months for all patients. Univariable analysis demonstrated that the 3 weeks during CCRT Grade (G) 4 lymphopenia (P=0.018), 2 months after CCRT G1-4 lymphopenia (P=0.004), 6 months after CCRT (6m-post-CCRT) G1-4 lymphopenia (P=0.001), and TLC nadir (P=0.020) were significantly associated with poorer OS. Multivariable analysis suggested that 6m-post-CCRT G1-4 lymphopenia (HR 2.614; P=0.041) were one of the independent predictors of OS. Further analysis inferred that radiation dose (OR: 1.328; P=0.005), GTV volume (OR: 1.004; P=0.036), and baseline TLC (OR: 0.288; P=0.001) were associated with 6m-post-CCRT lymphopenia. The persistent lymphopenia at 6 months after CCRT was an independent prognostic factor of OS in LA-NSCLC patients. Higher radiation dose, larger gross tumor volume and lower baseline TLC were significantly related to 6m-post-CCRT lymphopenia.