Peter Hass

Local tumor control probability modeling of primary and secondary lung tumors in stereotactic body radiotherapy

BACKGROUND AND PURPOSE To evaluate whether local tumor control probability (TCP) in stereotactic body radiotherapy (SBRT) varies between lung metastases of different primary cancer sites and between primary non-small cell lung cancer (NSCLC) and secondary lung tumors. MATERIALS AND METHODS A retrospective multi-institutional (n=22) database of 399 patients with stage I NSCLC and 397 patients with 525 lung metastases was analyzed. Irradiation doses were converted to biologically effective doses (BED). Logistic regression was used for local tumor control probability (TCP) modeling and the second-order bias corrected Akaike Information Criterion was used for model comparison. RESULTS After median follow-up of 19 months and 16 months (n.s.), local tumor control was observed in 87.7% and 86.7% of the primary and secondary lung tumors (n.s.), respectively. A strong dose-response relationship was observed in the primary NSCLC and metastatic cohort but dose-response relationships were not significantly different: the TCD90 (dose to achieve 90% TCP; BED of maximum planning target volume dose) estimates were 176 Gy (151-223) and 160 Gy (123-237) (n.s.), respectively. The dose-response relationship was not influenced by the primary cancer site within the metastatic cohort. CONCLUSIONS Dose-response relationships for local tumor control in SBRT were not different between lung metastases of various primary cancer sites and between primary NSCLC and lung metastases.

Stereotactic body radiotherapy (SBRT) for medically inoperable lung metastases—A pooled analysis of the German working group “stereotactic radiotherapy”

OBJECTIVES The current literature on stereotactic body radiotherapy (SBRT) for oligometastatic disease is characterized by small patient cohorts with heterogeneous primary tumors, metastases location and dose regimes. Hence, this study established a multi-institutional database of 700 patients treated with SBRT for pulmonary metastases to identify prognostic factors influencing survival and local control. MATERIALS AND METHODS All German radiotherapy departments were contacted and invited to participate in this analysis. A total number of 700 patients with medically inoperable lung metastases treated with SBRT in 20 centers between 1997 and 2014 were included in a database. Primary and metastatic tumor characteristics, treatment characteristics and follow-up data including survival, local control, distant metastases, and toxicity were evaluated. Lung metastases were treated with median PTV-encompassing single doses of 12.5Gy (range 3.0-33.0Gy) in a median number of 3 fractions (range 1-13). RESULTS After a median follow-up time of 14.3 months, 2-year local control (LC) and overall survival (OS) were 81.2% and 54.4%, respectively. In multivariate analysis, OS was most significantly influenced by pretreatment performance status, maximum metastasis diameter, primary tumor histology, time interval between primary tumor diagnosis and SBRT treatment and number of metastases. For LC, independent prognostic factors were pretreatment performance status, biological effective dose (BED) at PTV isocenter (BEDISO) and single fraction (PTV-encompassing) dose in multivariate analysis. Radiation-induced pneumonitis grade 2 or higher was observed in 6.5% of patients. The only factor significantly influencing toxicity was BEDISO (p=0.006). CONCLUSION SBRT for medically inoperable patients with pulmonary metastases achieved excellent local control and promising overall survival. Important prognostic factors were identified for selecting patients who might benefit most from this therapy approach.

Prospective randomized trial of enoxaparin, pentoxifylline and ursodeoxycholic acid for prevention of radiation-induced liver toxicity.

Background/Aim Targeted radiotherapy of liver malignancies has found to be effective in selected patients. A key limiting factor of these therapies is the relatively low tolerance of the liver parenchyma to radiation. We sought to assess the preventive effects of a combined regimen of pentoxifylline (PTX), ursodeoxycholic acid (UDCA) and low-dose low molecular weight heparin (LMWH) on focal radiation-induced liver injury (fRILI). Methods and Materials Patients with liver metastases from colorectal carcinoma who were scheduled for local ablation by radiotherapy (image-guided high-dose-rate interstitial brachytherapy) were prospectively randomized to receive PTX, UDCA and LMWH for 8 weeks (treatment) or no medication (control). Focal RILI at follow-up was assessed using functional hepatobiliary magnetic resonance imaging (MRI). A minimal threshold dose, i.e. the dose to which the outer rim of the fRILI was formerly exposed to, was quantified by merging MRI and dosimetry data. Results Results from an intended interim-analysis made a premature termination necessary. Twenty-two patients were included in the per-protocol analysis. Minimal mean hepatic threshold dose 6 weeks after radiotherapy (primary endpoint) was significantly higher in the study treatment-group compared with the control (19.1 Gy versus 14.6 Gy, p = 0.011). Qualitative evidence of fRILI by MRI at 6 weeks was observed in 45.5% of patients in the treatment versus 90.9% of the control group. No significant differences between the groups were observed at the 12-week follow-up. Conclusions The post-therapeutic application of PTX, UDCA and low-dose LMWH significantly reduced the extent and incidence fRILI at 6 weeks after radiotherapy. The development of subsequent fRILI at 12 weeks (4 weeks after cessation of PTX, UDCA and LMWH during weeks 1–8) in the treatment group was comparable to the control group thus supporting the observation that the agents mitigated fRILI. Trial Registration EU clinical trials register 2008-002985-70 ClinicalTrials.gov NCT01149304

The influence of different signal-to-background ratios on spatial resolution and F18-FDG-PET quantification using point spread function and time-of-flight reconstruction

BackgroundF18-fluorodeoxyglucose positron-emission tomography (FDG-PET) reconstruction algorithms can have substantial influence on quantitative image data used, e.g., for therapy planning or monitoring in oncology. We analyzed radial activity concentration profiles of differently reconstructed FDG-PET images to determine the influence of varying signal-to-background ratios (SBRs) on the respective spatial resolution, activity concentration distribution, and quantification (standardized uptake value [SUV], metabolic tumor volume [MTV]).MethodsMeasurements were performed on a Siemens Biograph mCT 64 using a cylindrical phantom containing four spheres (diameter, 30 to 70 mm) filled with F18-FDG applying three SBRs (SBR1, 16:1; SBR2, 6:1; SBR3, 2:1). Images were reconstructed employing six algorithms (filtered backprojection [FBP], FBP + time-of-flight analysis [FBP + TOF], 3D-ordered subset expectation maximization [3D-OSEM], 3D-OSEM + TOF, point spread function [PSF], PSF + TOF). Spatial resolution was determined by fitting the convolution of the object geometry with a Gaussian point spread function to radial activity concentration profiles. MTV delineation was performed using fixed thresholds and semiautomatic background-adapted thresholding (ROVER, ABX, Radeberg, Germany).ResultsThe pairwise Wilcoxon test revealed significantly higher spatial resolutions for PSF + TOF (up to 4.0 mm) compared to PSF, FBP, FBP + TOF, 3D-OSEM, and 3D-OSEM + TOF at all SBRs (each P < 0.05) with the highest differences for SBR1 decreasing to the lowest for SBR3. Edge elevations in radial activity profiles (Gibbs artifacts) were highest for PSF and PSF + TOF declining with decreasing SBR (PSF + TOF largest sphere; SBR1, 6.3%; SBR3, 2.7%). These artifacts induce substantial SUVmax overestimation compared to the reference SUV for PSF algorithms at SBR1 and SBR2 leading to substantial MTV underestimation in threshold-based segmentation. In contrast, both PSF algorithms provided the lowest deviation of SUVmean from reference SUV at SBR1 and SBR2.ConclusionsAt high contrast, the PSF algorithms provided the highest spatial resolution and lowest SUVmean deviation from the reference SUV. In contrast, both algorithms showed the highest deviations in SUVmax and threshold-based MTV definition. At low contrast, all investigated reconstruction algorithms performed approximately equally. The use of PSF algorithms for quantitative PET data, e.g., for target volume definition or in serial PET studies, should be performed with caution - especially if comparing SUV of lesions with high and low contrasts.

Male breast cancer: 20-year survival data for post-mastectomy radiotherapy.

Background: The goal of this population-based study was to determine the impact of post-mastectomy radiation therapy on long-term overall survival (OS) of male patients with breast cancer. Patients and Methods: We investigated 20-year OS rates of 664 patients diagnosed with primary stage I-III breast cancer in former East Germany between 1970 and 1989. Patients had a radical mastectomy with axillary lymph node dissection without systemic adjuvant therapy. Results: Median follow-up time was 26.2 years (range 19-38 years). 52.4% of the patients had post-mastectomy radiotherapy. Radiotherapy showed different effects in each stage group after 20 years. Whereas there was an OS trend for radiotherapy to harm patients with stage I disease (hazard ratio (HR) 1.45; 95% confidence interval (CI) 0.98-2.15; p = 0.065), radiotherapy showed no benefit in patients with stage II disease (HR 0.82; 95% CI 0.62-1.1; p = 0.15). There was a significant survival benefit for patients with stage III disease receiving radiotherapy (HR 0.60; 95% CI 0.41-0.88; p = 0.008). Conclusion: Post-mastectomy radiotherapy is associated with longer OS in male patients with stage III breast cancer. Male breast cancer patients at stages I and II do not seem to benefit from radiotherapy, but obsolete irradiation techniques might explain adverse long-term effects in earlier stages.

Accuracy of applicator tip reconstruction in MRI-guided interstitial 192Ir-high-dose-rate brachytherapy of liver tumors.

BACKGROUND AND PURPOSE To evaluate the reconstruction accuracy of brachytherapy (BT) applicators tips in vitro and in vivo in MRI-guided (192)Ir-high-dose-rate (HDR)-BT of inoperable liver tumors. MATERIALS AND METHODS Reconstruction accuracy of plastic BT applicators, visualized by nitinol inserts, was assessed in MRI phantom measurements and in MRI (192)Ir-HDR-BT treatment planning datasets of 45 patients employing CT co-registration and vector decomposition. Conspicuity, short-term dislocation, and reconstruction errors were assessed in the clinical data. The clinical effect of applicator reconstruction accuracy was determined in follow-up MRI data. RESULTS Applicator reconstruction accuracy was 1.6±0.5 mm in the phantom measurements. In the clinical MRI datasets applicator conspicuity was rated good/optimal in ⩾72% of cases. 16/129 applicators showed not time dependent deviation in between MRI/CT acquisition (p>0.1). Reconstruction accuracy was 5.5±2.8 mm, and the average image co-registration error was 3.1±0.9 mm. Vector decomposition revealed no preferred direction of reconstruction errors. In the follow-up data deviation of planned dose distribution and irradiation effect was 6.9±3.3 mm matching the mean co-registration error (6.5±2.5 mm; p>0.1). CONCLUSION Applicator reconstruction accuracy in vitro conforms to AAPM TG 56 standard. Nitinol-inserts are feasible for applicator visualization and yield good conspicuity in MRI treatment planning data. No preferred direction of reconstruction errors were found in vivo.

Efficacy and safety of image-guided interstitial single fraction high-dose-rate brachytherapy in the management of metastatic malignant melanoma.

Purpose Computed tomography (CT) or magnetic resonance imaging (MRI) guided brachytherapy provides high tumor control rates in hepatocellular carcinoma (HCC) and colorectal liver metastases. In contrast to thermal ablation methods such as radiofrequency ablation (RFA), much less restrictions apply with respect to tumor location or size. In this study, we determined the efficacy and safety of CT- or MRI-guided brachytherapy in metastatic melanoma. Material and methods Fifty-two metastases of malignant melanoma in 14 patients were included in this retrospective study. Local tumor control and safety were evaluated as primary and secondary endpoints. Furthermore, we evaluated overall survival and progression free survival. Tumor locations were liver (n = 31), lung (n = 15), adrenal (n = 3), lymph nodes (n = 2), and kidney (n = 1). Treatment planning was performed using three-dimensional CT or MRI data acquired after percutaneous applicator positioning under CT or open MRI guidance. Subsequently, single fraction high-dose-rate (HDR) brachytherapy was applied using a 192Iridium source. Clinical and cross-sectional follow-up were performed every 3 months post intervention. Results The median diameter of treated lesions was 1.5 cm (range: 0.7-10 cm). Doses between 15 and 20 Gy were applied (median dose: 19.9 Gy). The mean irradiation time ranged between 7-45 minutes. After treatment, there was one patient with a cholangitis. After a median follow up of five months, the median local tumor control was 90%. The median overall survival of the patients was 8 months. The median progression free survival of the patients was 6 months. Conclusions Image-guided HDR brachytherapy is a safe and effective treatment procedure in metastatic malignant melanoma.

Extending the Frontiers Beyond Thermal Ablation by Radiofrequency Ablation: SBRT, Brachytherapy, SIRT (Radioembolization)

Metastatic spread of the primary is still defined as the systemic stage of disease in treatment guidelines for various solid tumors. This definition is the rationale for systemic therapy. Interestingly and despite the concept of systemic involvement, surgical resection as a local treatment has proven to yield long-term outcomes in a subset of patients with limited metastatic disease, supporting the concept of oligometastatic disease. Radiofrequency ablation has yielded favorable outcomes in patients with hepatocellular carcinoma and colorectal metastases, and some studies indicate its prognostic potential in combined treatments with systemic therapies. However, some significant technical limitations apply, such as size limitation, heat sink effects, and unpredictable heat distribution to adjacent risk structures. Interventional and non-invasive radiotherapeutic techniques may overcome these limitations, expanding the options for oligometastatic patients and cytoreductive concepts. Current data suggest very high local control rates even in large tumors at any given location in the human body. The article focusses on the characteristics and possibilities of stereotactic body radiation therapy, interstitial high-dose-rate brachytherapy, and Yttrium-90 radioembolization. In this article, we discuss the differences of the technical preferences as well as their impact on indications. Current data is presented and discussed with a focus on application in oligometastatic or cytoreductive concepts in different tumor biologies.

Ultrasound-assisted catheter placement in CT-guided HDR brachytherapy for the local ablation of abdominal malignancies: Initial experience

PURPOSE  To evaluate the safety and feasibility of sonographically-assisted catheter placement in interstitial high-dose-rate brachytherapy of abdominal malignancies. MATERIALS AND METHODS  In an initial cohort of 12 patients and 16 abdominal tumors (colorectal liver metastases n = 9; renal cell cancer n = 3; hepatocellular carcinoma n = 2; cholangiocellular carcinoma n = 2), initial puncture and catheter placement for CT-guided brachytherapy were performed under sonographic assistance when possible. The interventional procedure was prospectively recorded and in-patient data were collected. All data underwent descriptive statistics and comparative analysis by the Mann-Whitney test. RESULTS  In 12 out of 16 lesions (diameter 1.5 - 12.9 cm), initial puncture was successfully achieved under ultrasound guidance without utilization of CT fluoroscopy, yielding a significantly shorter mean total fluoroscopy time (14.5 vs. 105.5 s; p = 0.006). In 8 lesions visibility was rated better in ultrasound than in CT fluoroscopy (p = 0.2). No major or minor complications occurred within 30 days after treatment. CONCLUSION  Ultrasound-assisted catheter placement during interstitial CT-guided brachytherapy of abdominal tumors could improve catheter positioning and reduce radiation exposure for medical staff. KEY POINTS  Ultrasound-assisted catheter placement in CT-guided brachytherapy is safe and feasible. Ultrasound puncture may improve catheter positioning. Reduced CT fluoroscopy time can significantly help to minimize radiation exposure for medical staff. CITATION FORMAT · Damm R, El-Sanosy S, Omari J et al. Ultrasound-assisted catheter placement in CT-guided HDR brachytherapy for the local ablation of abdominal malignancies: Initial experience. Fortschr Röntgenstr 2019; 191: 48 - 53.

Stereotactic body radiotherapy (SBRT) for multiple pulmonary oligometastases: Analysis of number and timing of repeat SBRT as impact factors on treatment safety and efficacy

BACKGROUND Stereotactic body radiotherapy (SBRT) for oligometastatic disease is characterized by an excellent safety profile; however, experiences are mostly based on treatment of one single metastasis. It was the aim of this study to evaluate safety and efficacy of SBRT for multiple pulmonary metastases. PATIENTS AND METHODS This study is based on a retrospective database of the DEGRO stereotactic working group, consisting of 637 patients with 858 treatments. Cox regression and logistic regression were used to analyze the association between the number of SBRT treatments or the number and the timing of repeat SBRT courses with overall survival (OS) and the risk of early death. RESULTS Out of 637 patients, 145 patients were treated for multiple pulmonary metastases; 88 patients received all SBRT treatments within one month whereas 57 patients were treated with repeat SBRT separated by at least one month. Median OS for the total patient population was 23.5 months and OS was not significantly influenced by the overall number of SBRT treatments or the number and timing of repeat SBRT courses. The risk of early death within 3 and 6 months was not increased in patients treated with multiple SBRT treatments, and no grade 4 or grade 5 toxicity was observed in these patients. CONCLUSIONS In appropriately selected patients, synchronous SBRT for multiple pulmonary oligometastases and repeat SBRT may have a comparable safety and efficacy profile compared to SBRT for one single oligometastasis.