Mean Tumor Dose Research Articles

Voxel-Based Dosimetry Predicts Local Tumor Progression Post 90Y Radiation Segmentectomy of Colorectal Liver Metastases

Background Radiation segmentectomy (RS) is an alternative potential local curative treatment for selected colorectal liver metastases (CLMs) not amenable to ablation or limited resection. Purpose The aim of this study was to evaluate the dosimetric response of low volume CLMs to RS in heavily pretreated patients who are not candidates for resection or percutaneous ablation. Patients and Methods This single-center retrospective study evaluated CLMs patients treated with RS (prescribed tumor dose >190 Gy) from 2015 to 2023. RS doses to tumor(s) and margins were calculated from SPECT/CT and PET/CT images. Response and local tumor progression (LTP) were assessed using anatomic (RECIST 1.1) and metabolic (PERCIST) criteria. LTP-free survival (LTPFS) and overall survival were estimated with Kaplan-Meier methodology. Variables were assessed as predictors of LTPFS using the Cox proportional hazards model. Results Thirty-six patients underwent 38 RS procedures to treat 57 tumors. Median time from initial diagnosis to detection of liver metastases and RS were 16.4 (interquartile range: 6.5–32.2) and 26.8 (interquartile range: 12.5–40.0) months, respectively. Median overall survival after RS was 14.3 (95% confidence interval [CI]: 10.8–30.7) months. Predictors of LTPFS included tumor number(s), mean tumor dose (MTD), and margin mean absorbed dose (MMAD). Complete radiographic (hazards ratio [HR]: 1.29e-16, 95% CI: 4.06e–17-4.07e-16, P < 0.001) and metabolic response (HR: 0.38, 95% CI: 0.15–0.95, P = 0.038) correlated with prolonged LTPFS. One-year LTPFS rate was 83.3% for tumors receiving MTD ≥400 Gy and a 5-mm surrounding MMAD ≥350 Gy (P = 0.006). No instances of LTP were observed when tumors received stereotactic irradiation over 300 Gy (at least 95% of the tumor volume received ≥300 Gy). One-year LTPFS rate for tumors receiving MTD ≥400 Gy was 68.6% versus 14.3% for those that did not reach this threshold (P = 0.013). In multivariate analysis, MTD ≥400 Gy and 5-mm MMAD ≥350 Gy were independent predictors of LTPFS (HR: 0.11; 95% CI: 0.01–0.81; P = 0.03). Conclusions MTD ≥400 Gy, MMAD ≥350 Gy, and stereotactic tumor irradiation ≥300 Gy are associated with prolonged LTPFS after RS for CLMs.

Voxel-based dosimetry with integrated Y-90 PET/MRI and prediction of response of primary and metastatic liver tumors to radioembolization with Y-90 glass microspheres.

In this study, we aimed to evaluate the response of the primary and metastatic liver tumors to radioembolization with 90Y glass microspheres and investigate its correlations with dosimetric variables calculated with 90Y PET/MRI. In this ambispective study, 44 patients treated with 90Y glass microspheres and imaged with 90Y PET/MRI were included for analysis. Dosimetric analysis was performed for every perfused lesion using dose-volume histograms. Response was assessed by comparing pre-treatment and follow-up total lesion glycolysis (TLG) values derived from 18F-FDG PET imaging. The relationship between ΔTLG and log-transformed dosimetric variables was analyzed with linear mixed effects regression models. ROC analyses were performed to compare discriminatory power of the variables in predicting response and complete response. Regression and ROC analyses demonstrated that mean tumor dose and almost all D values were statistically significant predictors of treatment response and complete treatment response. Specifically, D60, D70 and D80 values exhibited significantly higher discriminatory power for predicting treatment response compared to the mean dose (Dmean) delivered to tumor. High specificity cut-off values to predict response were determined as 160.75 Gy for Dmean, 95.50 Gy for D60, 89 Gy for D70, and 59.50 Gy for D80. Similarly, high-specificity cut-off values to predict complete response were 262.75 Gy for Dmean, 173 Gy for D70, 140.5 Gy for D80, and 100 Gy for D90. In this study, we demonstrated that voxel-based dosimetry with post-treatment 90Y PET/MRI can predict response to treatment. D60, D70 and D80 variables also did have greater discriminatory power compared to Dmean in prediction of response. In addition, we present high-specificity cut-offs to predict response (CR + PR) and complete response (CR) for both Dmean and several D variables derived from dose-volume histograms.

Resin-Based 90 Y Tumor Dose as a Predictor of Duration of Response and Survival in Patients With Surgically Unresectable Hepatocellular Carcinoma : A Prospective Single-Arm Study.

Personalized dosimetry improves overall survival (OS) in patients with hepatocellular carcinoma (HCC) treated with glass 90 Y radioembolization. This study evaluated personalized tumor dose (TD) as a predictor of OS, progression-free survival (PFS), and local duration of response (DOR) in patients with surgically unresectable HCC treated with resin 90 Y radioembolization. This prospective, single-center, single-arm clinical trial (NCT04172714) evaluated the efficacy of scout activity of resin 90 Y versus 99m Tc-MAA for treatment planning. A secondary aim of this study was to evaluate personalized dosimetry as a predictor of OS, PFS, and DOR. Partition dosimetry model was utilized for nonsegmental therapies with targeted TD >200 Gy and nontumoral liver dose <70 Gy. Single compartment dose of 200 Gy was used for segmentectomies. OS, PFS, and local DOR from 90 Y was estimated using Kaplan-Meier estimation with log-rank analysis used to determine predictors of prolonged survival. Thirty patients with treatment-naive HCC and 33 tumors (19 segmental and 14 nonsegmental) were included. Overall, 18 patients underwent segmental Y90-RE and 12 underwent non-segmental/lobar therapies. The mean 90 Y TD was 493 Gy. The median follow-up since enrollment into the study was 37 months. The mean OS was 32.2 months for the entire cohort. A total of 5 patients underwent orthotopic liver transplantation post 90 Y and were excluded from further survival analysis. The mean OS for the remainder of the cohort was 30.1 months (median not reached). The mean TD >250 Gy resulted in prolonged mean OS and PFS. The median local DOR was 32.7 months with mean TD 330 Gy predicting prolonged DOR. For patients with surgically unresectable HCC treated with resin 90 Y, there is mean TD threshold predicting prolonged OS, PFS, and local DOR. Therefore, there should be further emphasis on personalized dosimetry for optimization of patient outcomes.

Efficacy of Selective Internal Radiation Therapy for Hepatocellular Carcinoma Post-Incomplete Response to Chemoembolization.

Hepatocellular carcinoma (HCC) is one of the most common neoplasms worldwide and the third most common cause of cancer-related death. Several liver-targeted intra-arterial therapies are available for unresectable HCC, including selective internal radiation therapy (SIRT) and trans-arterial chemoembolization (TACE). Those two are the most used treatment modalities in localized non-operable HCC. TACE is the treatment option for patients with stage B, according to the BCLC staging system. In contrast, SIRT does not have an official role in the treatment algorithm, but recent studies showed promising outcomes in patients treated with SIRT. Although TACE is globally a safe procedure, it might provoke several vascular complications such as spasms, inflammatory constriction, and, in severe cases, occlusion, dissection, or collateralization. Hence, it is acclaimed that those complications could restrain the targeted response of the radio-embolization when we use it as second-line therapy post TACE. In this study, we will assess the efficacity of SIRT using Yttrium 90 Microspheres post incomplete or failure response to TACE. In our retrospective study, we had 23 patients who met the inclusion criteria. Furthermore, those patients have been followed radiologically and biologically. Then, we evaluated the therapeutic effect according to the mRECIST criteria, in addition to the personalized dose analysis. We found 8 patients were treated with TheraSphere®, with a median tumor absorbed dose of 445 Gy, while 15 received SIR-Spheres® treatment with a mean tumor dose of 268 Gy. After radiological analysis, 56.5% of the patients had a complete response, and 17.3% showed partial response, whereas 13% had stable disease and 13% had progressive disease. For patients treated with SIRT after an incomplete response or failure to TACE, we found an objective response rate of 73.8%. Despite the known vascular complications of TACE, SIRT can give a favorable response.

Holmium-166 Radioembolization of Hepatic Metastases in Salvage Setting: Preliminary Findings from a Single Center Experience

Abstract Purpose The aim of this study is to report the early outcomes of holmium-166 (166Ho) radioembolization in the treatment of liver metastases. Methods Nine patients with liver metastases originating from different primary sites were treated with 166Ho radioembolization between January 2019 and February 2020. The patients were assessed for pain using a visual analog scale (VAS) and quality of life (QoL) at various intervals during hospitalization and follow-up. Toxicity that may be attributable to radioembolization was graded according to CTCAE v5.0. The tumor dosimetry and tumor response were assessed with anatomic and metabolic imaging. Results The mean tumor dose was 150 Gy, 95% confidence interval (CI) was 135.2 to 164.8, with a range of 100 to 200 Gy based on single-photon emission computed tomography (SPECT)/CT, and distribution verified with inline T2/R2* magnetic resonance imaging (MRI) maps. No early (30-day) mortality or grade greater than 2 toxicities were noted, but one patient had chylous ascites. QoL assessed with the European Quality of Life 5-Dimensions 3-Level version (EQ-5D-3L) revealed mean index scores of 0.748 (range: 0.5–1), 95% CI of 0.6 to 0.9, before the procedure, and 0.7 (range: 0.5–1) and 95% CI of 0.6 to 0.8, at 1 month. The mean VAS was 70.6, 95% CI was 65.5 to 75.6, immediately after the procedure, and decreased to the mean VAS of 65.7 and 95% CI of 55.9 to 75.5 after 1 month. Five patients showed a partial response, three showed a stable disease, and one showed progressive disease at the first 2- to 3-month imaging follow-up. Conclusion Radioembolization with 166Ho microspheres for liver metastases appears to be safe, tolerable, and effective during the short term in this small-scale study.

Single-Compartment Dose Prescriptions for Ablative 90Y-Radioembolization Segmentectomy.

Yttrium-90 (90Y) radioembolization is increasingly being utilized with curative intent. While single-compartment doses with respect to the perfused volume for the complete pathologic necrosis (CPN) of tumors have been reported, the actual doses delivered to the tumor and at-risk margins that leads to CPN have hitherto not been estimated. We present an ablative dosimetry model that calculates the dose distribution for tumors and at-risk margins based on numerical mm-scale dose modeling and the available clinical CPN evidence and report on the necessary dose metrics needed to achieve CPN following 90Y-radioembolization. Three-dimensional (3D) activity distributions (MBq/voxel) simulating spherical tumors were modeled with a 121 × 121 × 121 mm3 soft tissue volume (1 mm3 voxels). Then, 3D dose distributions (Gy/voxel) were estimated by convolving 3D activity distributions with a 90Y 3D dose kernel (Gy/MBq) sized 61 × 61 × 61 mm3 (1 mm3 voxels). Based on the published data on single-compartment segmental doses for the resected liver samples of HCC tumors showing CPN after radiation segmentectomy, the nominal voxel-based mean tumor dose (DmeanCPN), point dose at tumor rim (DrimCPN), and point dose 2 mm beyond the tumor boundary (D2mmCPN), which are necessary to achieve CPN, were calculated. The single-compartment dose prescriptions to required achieve CPN were then analytically modeled for more general cases of tumors with diameters dt = 2, 3, 4, 5, 6, and 7 cm and with tumor-to-normal-liver uptake ratios T:N = 1:1, 2:1, 3:1, 4:1, and 5:1. The nominal case defined to estimate the doses needed for CPN, based on the previously published clinical data, was a single hyperperfused tumor with a diameter of 2.5 cm and T:N = 3:1, treated with a single-compartment segmental dose of 400 Gy. The voxel-level doses necessary to achieve CPN were 1053 Gy for the mean tumor dose, 860 Gy for the point dose at the tumor boundary, and 561 Gy for the point dose at 2 mm beyond the tumor edge. The single-compartment segmental doses necessary to satisfy the criteria for CPN in terms of the mean tumor dose, point dose at the tumor boundary, and the point dose at 2 mm beyond the tumor edge were tabulated for a range of tumor diameters and tumor-to-normal-liver uptake ratios. The analytical functions that describe the relevant dose metrics for CPN and, more importantly, the single-compartment dose prescriptions for the perfused volume needed to achieve CPN are reported for a large range of conditions in terms of tumor diameters (1-7 cm) and T:N uptake ratios (2:1-5:1).

Beyond Mean Tumor Dose: The Importance of Particle Density in Radioembolization

Beyond Mean Tumor Dose: The Importance of Particle Density in Radioembolization

Yttrium-90 Radiation Segmentectomy of Hepatocellular Carcinoma: A Comparative Study of the Effectiveness, Safety, and Dosimetry of Glass-Based versus Resin-Based Microspheres

PurposeTo evaluate the differences in safety, effectiveness, and dosimetry between glass-based and resin-based ablative yttrium-90 (90Y) transarterial radioembolization (TARE) of hepatocellular carcinoma (HCC). Materials and MethodsUsing the modified Response Evaluation Criteria in Solid Tumors and Common Terminology Criteria for Adverse Events, both tumor response and adverse events (AEs) were assessed at 3 months after 90Y-TARE. Post procedure 90Y-bremsstrahlung single-photon emission computed tomography/computed tomography voxel-based dosimetry analysis was used to create tumor dose (TD) and normal tissue dose (NTD) volume histograms, and to calculate tumor particle loading and specific activity. The TD and NTD receiver operating characteristic curves evaluated the dose threshold able to predict objective (partial or complete) and complete tumor responses in addition to any-grade and grade ≥3 AE incidences. The chi-square test and Student t-test were used to assess variable differences where appropriate. ResultsBetween 2019 and 2020, 81 patients with HCC (20 in the resin-based cohort and 61 in the glass-based cohort) underwent ablative 90Y-TARE. The resin-based cohort had more males (89% vs 65%, P = .03), lower tumor-to-normal ratio (1.81 ± 0.39 vs 2.22 ± 0.94, P = .03), higher tumor particle loading (40,172 particles/mL ± 28,039 vs 17,081 particles/mL ± 12,555, P = .0001), lower specific activity (158 Bq/particle ± 3 vs 1,058 Bq/particle ± 331, P = .001), and lower mean TD (308 Gy ± 210 vs 794 Gy ± 523, P = .0002) than the glass-based cohort. No significant differences in baseline characteristics or posttreatment AEs were noted. The overall objective and complete response rates were 85% (95% resin-based vs 82% glass-based; P = .1) and 65% (95% resin-based vs 56% glass-based; P = .003), respectively. The mean TD thresholds able to predict the objective and complete responses were 176 Gy and 247 Gy for resin-based radioembolization and 290 Gy and 481 Gy for glass-based radioembolization, respectively. A maximum NTD of 999 Gy predicted any-grade AEs in glass-based ablative 90Y-TARE. ConclusionsCompared with glass-based ablative 90Y-TARE, resin-based ablative 90Y-TARE can offer comparable safety and effectiveness profiles for patients with HCC. The impact of the significantly different tumor particle loading, particle specific activities, and delivered TDs on tumor response outcomes merits further investigation.

Voxel-based dosimetry predicting treatment response and related toxicity in HCC patients treated with resin-based Y90 radioembolization: a prospective, single-arm study

BackgroundThere is an increasing body of evidence indicating Y90 dose thresholds for tumor response and treatment-related toxicity. These thresholds are poorly studied in resin Y90, particularly in hepatocellular carcinoma (HCC).PurposeTo evaluate the efficacy of prospective voxel-based dosimetry for predicting treatment response and adverse events (AEs) in patients with HCC undergoing resin-based Y90 radioembolization.Materials and methodsThis correlative study was based on a prospective single-arm clinical trial (NCT04172714), which evaluated the efficacy of low/scout (555 MBq) activity of resin-based Y90 for treatment planning. Partition model was used with goal of tumor dose (TD) > 200 Gy and non-tumoral liver dose (NTLD) < 70 Gy for non-segmental therapies. Single compartment dose of 200 Gy was used for segmentectomies. Prescribed Y90 activity minus scout activity was administered for therapeutic Y90 followed by Y90-PET/CT. Sureplan® (MIM Software, Cleveland, OH) was used for dosimetry analysis. Treatment response was evaluated at 3 and 6 months. Receiver operating characteristic curve determined TD response threshold for objective response (OR) and complete response (CR) as well as non-tumor liver dose (NTLD) threshold that predicted AEs.ResultsN = 30 patients were treated with 33 tumors (19 segmental and 14 non-segmental). One patient died before the first imaging, and clinical follow-up was excluded from this analysis. Overall, 26 (81%) of the tumors had an OR and 23 (72%) had a CR. A mean TD of 253 Gy predicted an OR with 92% sensitivity and 83% specificity (area under the curve (AUC = 0.929, p < 0.001). A mean TD of 337 Gy predicted a CR with 83% sensitivity and 89% specificity (AUC = 0.845, p < 0.001). A mean NTLD of 81 and 87 Gy predicted grade 3 AEs with 100% sensitivity and 100% specificity in the non-segmental cohort at 3- and 6-month post Y90, respectively.ConclusionIn patients with HCC undergoing resin-based Y90, there are dose response and dose toxicity thresholds directly affecting outcomes.Clinical trial number: NCT04172714.

Personalized mid-course FDG-PET based adaptive treatment planning for non-small cell lung cancer using machine learning and optimization

Objective. Traditional radiotherapy (RT) treatment planning of non-small cell lung cancer (NSCLC) relies on population-wide estimates of organ tolerance to minimize excess toxicity. The goal of this study is to develop a personalized treatment planning based on patient-specific lung radiosensitivity, by combining machine learning and optimization. Approach. Sixty-nine non-small cell lung cancer patients with baseline and mid-treatment [18]F-fluorodeoxyglucose (FDG)-PET images were retrospectively analyzed. A probabilistic Bayesian networks (BN) model was developed to predict the risk of radiation pneumonitis (RP) at three months post-RT using pre- and mid-treatment FDG information. A patient-specific dose modifying factor (DMF), as a surrogate for lung radiosensitivity, was estimated to personalize the normal tissue toxicity probability (NTCP) model. This personalized NTCP was then integrated into a NTCP-based optimization model for RT adaptation, ensuring tumor coverage and respecting patient-specific lung radiosensitivity. The methodology was employed to adapt the treatment planning of fifteen NSCLC patients. Main results. The magnitude of the BN predicted risks corresponded with the RP severity. Average predicted risk for grade 1–4 RP were 0.18, 0.42, 0.63, and 0.76, respectively (p < 0.001). The proposed model yielded an average area under the receiver-operating characteristic curve (AUROC) of 0.84, outperforming the AUROCs of LKB-NTCP (0.77), and pre-treatment BN (0.79). Average DMF for the radio-tolerant (RP grade = 1) and radiosensitive (RP grade ≥ 2) groups were 0.8 and 1.63, p < 0.01. RT personalization resulted in five dose escalation strategies (average mean tumor dose increase = 6.47 Gy, range = [2.67–17.5]), and ten dose de-escalation (average mean lung dose reduction = 2.98 Gy [0.8–5.4]), corresponding to average NTCP reduction of 15% [4–27]. Significance. Personalized FDG-PET-based mid-treatment adaptation of NSCLC RT could significantly lower the RP risk without compromising tumor control. The proposed methodology could help the design of personalized clinical trials for NSCLC patients.

Accuracy and Safety of Scout Dose Resin Yttrium-90 Microspheres for Radioembolization Therapy Treatment Planning: A Prospective Single-Arm Clinical Trial

PurposeTo compare the accuracy and safety of 0.56 GBq resin yttrium-90 (90Y) (scout90Y) microspheres with those of technetium-99m macroaggregated albumin (MAA) in predicting the therapeutic 90Y (Rx90Y) dose for patients with hepatocellular carcinoma (HCC). Materials and MethodsThis prospective single-arm clinical trial (Clinicaltrials.gov: NCT04172714) recruited patients with HCC. Patients underwent same-day mapping with MAA and scout90Y. Rx90Y activity was administered 3 days after mapping. Using paired t test and Pearson correlation, the tumor-to-normal ratio (TNR), lung shunt fraction (LSF), predicted mean tumor dose (TD), and nontumoral liver dose (NTLD) by MAA and scout90Y were compared with those by Rx90Y. Bland-Altman plots compared the level of agreement between the TNR and LSF of scout90Y and MAA with that of Rx90Y. The safety of scout90Y was evaluated by examining the discrepancy in extrahepatic activity between MAA and scout90Y. ResultsThirty patients were treated using 19 segmental and 14 nonsegmental (ie, 2 contiguous segments or nonsegmental) therapies. MAA had weak LSF, moderate TNR, and moderate TD linear correlation with Rx90Y. Scout90Y had a moderate LSF, strong TNR, strong TD, and very strong NTLD in correlation with those of Rx90Y. Furthermore, the TNR and LSF of scout90Y had a stronger agreement with those of Rx90Y than with those of MAA. In the nonsegmental subgroup, MAA had no significant correlation with the TD and NTLD of Rx90Y, whereas scout90Y had a very strong correlation with both of these factors. In the segmental subgroup, both MAA and scout90Y had a strong linear correlation with the TD and NTLD of Rx90Y. ConclusionsCompared with MAA, scout90Y is a more accurate surrogate for Rx90Y biodistribution for nonsegmental therapies.

Hearing Loss in Cancer Patients with Skull Base Tumors Undergoing Pencil Beam Scanning Proton Therapy: A Retrospective Cohort Study.

Simple SummaryMost patients with skull base tumors require radiation therapy as part of their overall treatment, preferably with protons. However, vital and healthy organs, such as the cochlea, are often located in the immediate anatomical vicinity of the tumor. Despite the high precision of the proton beam, irradiating the cochlea is often unavoidable, resulting in an increased risk of hearing loss. To assess the frequency and severity of changes in hearing after proton therapy, we performed a retrospective study in a cohort of 51 patients undergoing proton therapy for skull base tumors. We observed that a hearing threshold shift correlates to the applied radiation dose intensity to the cochlea. In addition, advancing age, hearing sensitivity before proton therapy, and the time elapsed after the end of proton therapy are independently associated with the deterioration of the hearing threshold after proton therapy. These results are essential to adequately inform patients about the treatment’s impact and side effects.To assess the incidence and severity of changes in hearing threshold in patients undergoing high-dose pencil-beam-scanning proton therapy (PBS-PT). This retrospective cohort study included fifty-one patients (median 50 years (range, 13–68)) treated with PBS-PT for skull base tumors. No chemotherapy was delivered. Pure tone averages (PTAs)were determined before (baseline) and after PBS-PT as the average hearing thresholds at frequencies of 0.5, 1, 2, and 4 kHz. Hearing changes were calculated as PTA differences between pre-and post-PBS-PT. A linear mixed-effects model was used to assess the relationship between the PTA at the follow-up and the baseline, the cochlea radiation dose intensity, the increased age, and the years after PBS-PT. Included patients were treated for chordoma (n = 24), chondrosarcoma (n = 9), head and neck tumors (n = 9), or meningioma (n = 3), with a mean tumor dose of 71.1 Gy (RBE) (range, 52.0–77.8), and a mean dose of 37 Gy (RBE) (range, 0.0–72.7) was delivered to the cochleas. The median time to the first follow-up was 11 months (IQR, 5.5–33.7). The PTA increased from a median of 15 dB (IQR 10.0–25) at the baseline to 23.8 (IQR 11.3–46.3) at the first follow-up. In the linear mixed-effect model, the baseline PTA (estimate 0.80, 95%CI 0.64 to 0.96, p ≤ 0.001), patient’s age (0.30, 0.03 to 0.57, p = 0.029), follow-up time (2.07, 0.92 to 3.23, p ≤ 0.001), and mean cochlear dose in Gy (RBE) (0.34, 0.21 to 0.46, p ≤ 0.001) were all significantly associated with an increase in PTA at follow-up. The applied cochlear dose and baseline PTA, age, and time after treatment were significantly associated with hearing loss after proton therapy.

Effect of Peptide Dose on Radiation Dosimetry for Peptide Receptor Radionuclide Therapy with 177Lu-DOTATOC: A Pilot Study.

Background:Optimal peptide concentration in treatment with 177Lu-DOTATOC/DOTATATE is a matter of debate. Most of the studies with peptide receptor radionuclide therapy mention peptide dose ranging between 100 and 250 μg. The aim of this is to identify possible differences in radiation-absorbed doses (D/Gy) to tumor and kidney as a function of the peptide mass dose in order to identify the most suitable peptide dose for treatment. The therapeutic index (Dtumor/Dkidneys) was assessed as a key parameter for the treatment response.Materials and Methods:Five patients with metastasized Grade 1 to Grade 2 neuroendocrine tumor were analyzed in this study. Patients (n = 4) received two cycles of treatment with intravenously injected 177Lu-DOTATOC containing peptide mass doses of 200 μg and 90 μg, alternatively; one patient was treated with 90 μg peptide mass in both the therapy cycles. Whole-body (head to mid-thigh) three-dimensional single-photon emission computerized tomography (3D SPECT)/CT images were acquired at 1, 4, 24, 48, and 72 h following the injection of 177Lu-DOTATOC. Attenuation correction for 3D SPECT images was performed using CT data acquired and fused with the SPECT data (SPECT/CT).Results:Overall, 28 target lesions (liver n = 17, lung n = 4, lymph nodes n = 1, and bone n = 2) were analyzed after 1st and 2nd therapy cycles. Tumor normalized absorbed doses varied by a factor of 74 between 0.35 and 26 mGy/MBq. Averaged over all patients, a higher normalized mean tumor dose (10.51 mGy/MBq) was achieved for a peptide dose of 200 μg compared to 90 μg (4.58 mGy/MBq). Kidneys doses varied by a factor of up to 4 between patients (0.25–1.0 mGy/MBq) (independent of dose cycle and peptide dose) and by a factor of up to 2 between dose cycles. The mean kidney dose was 13.7% higher for the 90 μg peptide dose compared to 200 μg. Given the higher tumor dose, the mean therapeutic index of a 200 μg mass dose was considerably higher (16.95), compared to a 90 μg mass dose (9.63). This coincided with the observation, that lesion volume reduction was more pronounced after an initial treatment with a 200 μg mass dose. Biologically effective dose was only 5. 1%–19.3% higher than the absorbed dose for individual dose cycles.Conclusions:Higher peptide dose of 200 μg appears to be more suitable than 90 μg in terms of tumor dose, kidney dose, and therapeutic index for treatment with 177Lu-DOTATOC.

Role of Resin Microsphere Y90 Dosimetry in Predicting Objective Tumor Response, Survival and Treatment Related Toxicity in Surgically Unresectable Colorectal Liver Metastasis: A Retrospective Single Institution Study.

Simple SummaryColorectal liver metastases are difficult to treat, with only a minority of patients eligible for surgical resection. Yttrium-90 selective internal radiation therapy is an alternative treatment currently used for patients who have progressed on chemotherapy. A technique called dosimetry allows clinicians to analyze how much radiation was delivered to target lesions post-treatment. The aim of this study is to evaluate the relationship of various dosimetric parameters with objective tumor response, overall survival, and treatment related toxicity with the potential goal of optimizing Yttrium-90 treatment in this patient population. Additionally, other potential predictors of survival outcomes, including clinical and demographic factors, were also evaluated. We found that delivering a mean tumor dose ≥100 Gy when using resin microspheres was significantly associated with objective tumor response and prolonged overall survival. In this study, no mean non-tumoral liver dose threshold was found to predict treatment related toxicity.Purpose: To Evaluate the correlation between tumor dosimetric parameters with objective tumor response (OR) and overall survival (OS) in patients with surgically unresectable colorectal liver metastasis (CRLM) undergoing resin-based Ytrrium-90 selective internal radiation therapy (Y90 SIRT). Materials and Methods: 45 consecutive patients with CRLM underwent resin-based Y90 SIRT in one or both hepatic lobes (66 treated lobes total). Dose volume histograms were created with MIM Sureplan® v.6.9 using post-treatment SPECT/CT. Dosimetry analyses were based on the cumulative volume of the five largest tumors in each treatment session and non-tumoral liver (NTL) dose. Receiver operating characteristic (ROC) curve was used to evaluate tumor dosimetric factors in predicting OR by Response Evaluation Criteria for Solid Tumors at 3 months post-Y90. Additionally, ROC curve was used to evaluate non-tumoral liver dose as a predictor of grade ≥ 3 liver toxicity and radioembolization induced liver disease (REILD) 3 months post Y90. To minimize for potential confounding demographic and clinical factors, univariate and multivariate analysis of survival with mean tumor dose as one of the factors were also performed. Kaplan-Meier estimation was used for OS analysis from initial Y90 SIRT. Results: 26 out of 45 patients had OR with a median OS of 17.2 months versus 6.8 months for patients without OR (p < 0.001). Mean tumor dose (TD) of the five largest tumors was the strongest predictor of OR with an area under the curve of 0.73 (p < 0.001). Minimum TD, and TD to 30%, 50%, and 70% of tumor volume also predicted OR (p’s < 0.05). Mean TD ≥ 100 Gy predicted a significantly prolonged median OS of 19 vs. 11 months for those receiving TD < 100 Gy (p = 0.016). On univariate analysis, mean TD < 100 Gy, presence of any genomic mutation, presence of MAPK pathway mutation, bilobar hepatic metastases and diffuse metastatic disease (>10 lesions per liver lobe) were found to be predictors of shorter median OS. On multivariate analysis, mean TD < 100 Gy, presence of any genomic mutation, and diffuse hepatic metastatic disease were found to be independent predictors of shorter OS. Overall, six (13.3%) patients developed grade ≥ 3 liver toxicity post Y90 of whom two (4.4%) patients developed REILD. No dose threshold predicting grade ≥ 3 liver toxicity or REILD was identified. Conclusions: Mean TD ≥ 100 Gy in patients with unresectable CRLM undergoing resin-based Y90 SIRT predicts OR and prolonged OS.

Determination of Tumor Dose Response Thresholds in Patients with Chemorefractory Intrahepatic Cholangiocarcinoma Treated with Resin and Glass-based Y90 Radioembolization.

To compare the efficacies of glass and resin-based Yttrium-90 microspheres by comparing absorbed tumor dose (TD) with both tumor response (TR) and overall survival (OS) in patients with chemorefractory intrahepatic cholangiocarcinoma (ICC). Post-Y90 treatment bremsstrahlung SPECT/CT of 38 consecutive patients receiving 45 treatments (21 resin microspheres, 24 glass microspheres) were analyzed retrospectively. MIM software v6.9.4 (MIM Software Inc, Cleveland, OH) was used to calculate targeted tumors' dose volume histogram. Modified Response Evaluation Criteria in Solid Tumors was used to evaluate tumor response 3months post-treatment. Kaplan Meier estimation was used for survival analysis. T-test was used to compare the devices on various dosimetric parameters. Thresholds for TD to predict TR with ≥ 80% specificity were as follows: mean TD (Resin: 78.9Gy; Glass: 254.7Gy), maximum TD (Resin: 162.9Gy; Glass: 591Gy), minimum TD (Resin: 53.7Gy; Glass: 149.1Gy). Microsphere type had no effect on survival from first Y90 (Resin: 11.2 mo; Glass 10.9 mo [p = 0.548]). In patients receiving resin microspheres, mean TD ≥ 75Gy or maximum TD ≥ 150Gy was associated with median OS of 20.2 mo compared to 6.5 mo for those receiving less (p = 0.001, 0.002, respectively). For patients treated with glass microspheres, those receiving a mean TD ≥ 150Gy had a median OS of 14.6 mo vs. 2.6 mo for those receiving less (p = 0.031). TD thresholds predictive of TR and OS differ significantly between glass and resin microspheres. However, microsphere type has no impact on survival in patients with chemorefractory ICC. Level 3, Retrospective Study.

What is the optimal treatment for T1N0 anal squamous cell carcinoma? Analysis of current practices in the prospective French FFCD ANABASE cohort

Introductionfor localized T1N0 squamous cell carcinoma of the anus (SCCA) standard radiotherapy (RT) may result in overtreatment and alternative strategies are debated. MethodsT1N0M0 SCCA treated between 2015 and 2020 by local excision (LE) or RT were analyzed from the French prospective FFCD ANABASE cohort. Treatment strategies, recurrence-free and colostomy-free survivals (RFS, CFS) and prognostic factors were reported. Resultsamong 1135 SCCA patients, 99 T1N0M0 were treated by LE(n = 17,17.2%), or RT (n = 82,82.8%) including RT alone (n = 65,79.2%) or chemo-RT (n = 17, 20.7%). Median follow-up was 27.2 months [0.03–54.44]. Median tumor size were 11.4 mm [0.9–20] and 15.3 mm [2–20] in the LE and RT groups respectively. Mean RT tumor dose was 59.4 Gy [18–69.4 Gy]. One patient in LE group and 9 in RT group had a pelvic recurrence, either local (60%), nodal (10%) or both (30%). RFS and CFS at 24 months were 92.2%[95%CI,83.4–96.4] and 94.6%[95%CI,86.1–98.0], at 36 months 88.1%[95%CI,77.1–94.2] and 88.5%[95%CI,77.0–94.5], in LE and RT group respectively, without any significative difference (HR = 0.57;[95%CI,0.07–4.45];p = 0.60). By univariate analysis, male gender was the only prognostic factor(HR = 5.57;95%CI, 1.76–17.63; p = 0.004). Conclusionthis cohort confirms the heterogeneity of T1N0M0 SCCA management, questioning the place of RT alone, reduced dose or RT volume, and the safety of LE.

Salvage Boron Neutron Capture Therapy for Malignant Brain Tumor Patients in Compliance with Emergency and Compassionate Use: Evaluation of 34 Cases in Taiwan.

Simple SummaryAlthough boron neutron capture therapy (BNCT) is a promising therapeutic approach for malignant brain tumors, the optimal BNCT parameters for patients with life-threatening, end-stage brain tumors remain unclear. The results of this study show that for life-threatening, end-stage brain tumor patients, BNCT is a promising therapeutic modality that is associated with an overall survival time of 7.25 months and no severe adverse events (grade ≥ 3). Remarkably, patients who achieved a complete response had overall survival times and cancer-specific survival times of up to 17.66 and 22.5 months, respectively. In addition, since these patients are usually physically weak and already on the verge of life-threatening conditions, reducing the BNCT dose still has good therapeutic outcomes. Statistical analysis revealed the optimal BNCT parameters and tumor characteristics, including a tumor-to-normal tissue (T/N) uptake ratio of ≥4, a tumor volume of <20 mL, a mean tumor dose of ≥25 Gy-E, MIB-1 ≤ 40, and a lower recursive partitioning analysis (RPA) class. The results of this study provide a reference for other clinicians or radiation oncologists conducting BNCT treatment for such patients.Although boron neutron capture therapy (BNCT) is a promising treatment option for malignant brain tumors, the optimal BNCT parameters for patients with immediately life-threatening, end-stage brain tumors remain unclear. We performed BNCT on 34 patients with life-threatening, end-stage brain tumors and analyzed the relationship between survival outcomes and BNCT parameters. Before BNCT, MRI and 18F-BPA-PET analyses were conducted to identify the tumor location/distribution and the tumor-to-normal tissue uptake ratio (T/N ratio) of 18F-BPA. No severe adverse events were observed (grade ≥ 3). The objective response rate and disease control rate were 50.0% and 85.3%, respectively. The mean overall survival (OS), cancer-specific survival (CSS), and relapse-free survival (RFS) times were 7.25, 7.80, and 4.18 months, respectively. Remarkably, the mean OS, CSS, and RFS of patients who achieved a complete response were 17.66, 22.5, and 7.50 months, respectively. Kaplan–Meier analysis identified the optimal BNCT parameters and tumor characteristics of these patients, including a T/N ratio ≥ 4, tumor volume < 20 mL, mean tumor dose ≥ 25 Gy-E, MIB-1 ≤ 40, and a lower recursive partitioning analysis (RPA) class. In conclusion, for malignant brain tumor patients who have exhausted all available treatment options and who are in an immediately life-threatening condition, BNCT may be considered as a therapeutic approach to prolong survival.

Determination of tumour dose response threshold and implication on survival in patients with HCC treated with Y90 radiation segmentectomy: a simple semi-quantitative analysis.

To evaluate the relationship between Yttrium-90 (Y90) tumour dose and response rate in patients with hepatocellular carcinoma (HCC) who undergo Y90 radiation segmentectomy (Y90-RS) and to determine implication on overall survival (OS). Post Y90-RS Bremsstrahlung single-photon emission computed tomography/CT of 105 HCC patients with 110 treatments performed with glass microspheres was retrospectively analysed. The dose-volume histogram of the targeted tumour was determined with commercially available dosimetry software. Tumour response at 3 months was evaluated using modified Response Evaluation Criteria in Solid Tumours. Tumour dose thresholds associated with the objective response with 80% specificity were then used to evaluate implication on OS using Kaplan-Meier estimation and log-rank analysis. Tumour dose thresholds to predict objective response with 80% specificity were the following: maximum tumour dose (748 Gy), mean tumour dose (568 Gy), minimum tumour dose of 30% tumour volume (608 Gy), minimum tumour dose of 50% tumour volume (565 Gy), minimum tumour dose of 70% tumour volume (464 Gy) and minimum tumour dose of 100% tumour volume (213 Gy). These parameters all significantly predicted tumour response with areas under the ROC curve of >0.6. Mean tumour dose of ≥250 Gy predicted median OS of 43.67 vs. 17.87 months for others (P = 0.026). Minimum dose ≥180 Gy to 100% of tumour volume predicted median OS of 44.93 vs. 35.87 months for others (P = 0.043). In patients with HCC undergoing Y90-RS, mean tumour dose ≥250 Gy and minimum tumour dose of ≥180 Gy to 100% of tumour volume are both significantly correlated with higher objective tumour response and prolonged survival.

Radiotherapeutic treatment options for oligotopic malignant liver lesions

BackgroundSeveral radiotherapeutic approaches for patients with oligotopic malignant liver lesions unfit for surgical resection exist. The most advanced competitive techniques are high-dose-rate (HDR) brachytherapy, Cyberknife, volume-modulated-arc therapy (VMAT) and Tomotherapy. We evaluated the optimal technique by a planning study for a single ablative dose with different lesion sizes.MethodsWe compared dose distributions of HDR-brachytherapy with stereotactic ablative radiotherapy using the Cyberknife, VMAT or Tomotherapy. Tumor-control-probabilities (TCP), normal-tissue-complication-probabilities (NTCP) were determined in a theoretical framework applying a single dose of 20 Gy (demanding 95% coverage) for intrahepatic lesions of 1–5 cm in size. We evaluated therapeutic ratios by TCP (mean dose in the lesion) relative to high-dose (conformality) or low-dose liver exposition in dependency on the lesion size for each technique. In addition, we considered treatment times and accuracy (clinical target volume vs planning target volume).ResultsHDR-brachtherapy has the highest therapeutic ratios with respect to high-dose as well as low-dose liver exposition even for extended lesions, and the Cyberknife being suited second best. However, for lesions ≥ 3 cm diameter the therapeutic ratios of all ablative techniques are increasingly converging, and better tolerance and shorter treatment times of noninvasive external techniques become more important. On the other hand, mean tumor doses of HDR-brachytherapy of near 60 Gy are unattainable by the other techniques gaining only 22–34 Gy, and the conformality of HDR-brachytherapy is still rather good for lesions ≥ 3 cm diameter.ConclusionsHDR-brachytherapy is by far the most effective technique to treat intrahepatic lesions by a single fraction, but sparing of the surroundings declines with increasing lesion size and approaches the benchmarks of external beam radiosurgery techniques. External beam radiotherapy has the advantage to use suitable fractionation schedules.

Correlation of an Index-Lesion-Based SPECT Dosimetry Method with Mean Tumor Dose and Clinical Outcome after 177Lu-PSMA-617 Radioligand Therapy.

Background: Dosimetry can tailor prostate-specific membrane-antigen-targeted radioligand therapy (PSMA-RLT) for metastatic castration-resistant prostate cancer (mCRPC). However, whole-body tumor dosimetry is challenging in patients with a high tumor burden. We evaluate a simplified index-lesion-based single-photon emission computed tomography (SPECT) dosimetry method in correlation with clinical outcome. Methods: 30 mCRPC patients were included (median 71 years). The dosimetry was performed for the first cycle using quantitative 177Lu-SPECT. The response was evaluated using RECIST 1.1 and PERCIST criteria, as well as changes in PSMA-positive tumor volume (PSMA-TV) in post-therapy PSMA-PET and biochemical response according to PSA changes after two RLT cycles. Results: Mean tumor doses as well as index-lesion doses were significantly higher in PERCIST responders compared to non-responders (10.2 ± 12.0 Gy/GBq vs. 4.0 ± 2.9 Gy/GBq, p = 0.03 and 13.7 ± 14.2 Gy/GBq vs. 5.9 ± 4.4 Gy/GBq, p = 0.04, respectively). No significant differences in mean tumor and index lesion doses were observed between responders and non-responders according to RECIST 1.1, PSMA-TV, and biochemical response criteria. Conclusion: Compared to mean tumor doses on a patient level, single index-lesion-based SPECT dosimetry correlates equally well with the response to PSMA-RLT according to PERCIST criteria and may represent a fast and feasible dosimetry approach for clinical routine.