Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: At the first interim analysis of the phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study, the addition of pembrolizumab to chemoradiotherapy provided a statistically significant and clinically meaningful improvement in progression-free survival in patients with locally advanced cervical cancer. We report the overall survival results from the second interim analysis of this study. METHODS: Eligible patients with newly diagnosed, high-risk (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA regardless of nodal status), locally advanced, histologically confirmed, squamous cell carcinoma, adenocarcinoma, or adenosquamous cervical cancer were randomly assigned 1:1 to receive five cycles of pembrolizumab (200 mg) or placebo every 3 weeks with concurrent chemoradiotherapy, followed by 15 cycles of pembrolizumab (400 mg) or placebo every 6 weeks. Pembrolizumab or placebo and cisplatin were administered intravenously. Patients were stratified at randomisation by planned external beam radiotherapy type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), cervical cancer stage at screening (FIGO 2014 stage IB2-IIB node positive vs III-IVA), and planned total radiotherapy (external beam radiotherapy plus brachytherapy) dose (<70 Gy vs ≥70 Gy [equivalent dose of 2 Gy]). Primary endpoints were progression-free survival per RECIST 1.1 by investigator or by histopathological confirmation of suspected disease progression and overall survival defined as the time from randomisation to death due to any cause. Safety was a secondary endpoint. FINDINGS: Between June 9, 2020, and Dec 15, 2022, 1060 patients at 176 sites in 30 countries across Asia, Australia, Europe, North America, and South America were randomly assigned to treatment, with 529 patients in the pembrolizumab-chemoradiotherapy group and 531 patients in the placebo-chemoradiotherapy group. At the protocol-specified second interim analysis (data cutoff Jan 8, 2024), median follow-up was 29·9 months (IQR 23·3-34·3). Median overall survival was not reached in either group; 36-month overall survival was 82·6% (95% CI 78·4-86·1) in the pembrolizumab-chemoradiotherapy group and 74·8% (70·1-78·8) in the placebo-chemoradiotherapy group. The hazard ratio for death was 0·67 (95% CI 0·50-0·90; p=0·0040), meeting the protocol-specified primary objective. 413 (78%) of 528 patients in the pembrolizumab-chemoradiotherapy group and 371 (70%) of 530 in the placebo-chemoradiotherapy group had a grade 3 or higher adverse event, with anaemia, white blood cell count decreased, and neutrophil count decreased being the most common adverse events. Potentially immune-mediated adverse events occurred in 206 (39%) of 528 patients in the pembrolizumab-chemoradiotherapy group and 90 (17%) of 530 patients in the placebo-chemoradiotherapy group. This study is registered with ClinicalTrials.gov, NCT04221945. INTERPRETATION: Pembrolizumab plus chemoradiotherapy significantly improved overall survival in patients with locally advanced cervical cancer These data, together with results from the first interim analysis, support this immuno-chemoradiotherapy strategy as a new standard of care for this population. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co.

Timing of development of osteoradionecrosis post head and neck radiotherapy: does a safe time interval exist for dental extraction?

INTRODUCTION: Risk factors for developing osteoradionecrosis (ORN) are well known, but less is known about factors influencing the interval between radiotherapy and the onset of ORN. Also, it is unknown whether there is any specific period post-radiotherapy with a reduced probability of ORN when irradiated teeth require extraction. PURPOSE: The primary aim of this study was to identify factors influencing the interval in developing ORN in the following subgroups of patients: (1) patients who spontaneously developed ORN, (2) surgical-intervention-related ORN with a particular focus on patients after mandibulectomy. The secondary aim was to attempt to identify a possible time for safer dental intervention after primary treatment. MATERIALS AND METHODS: The authors retrospectively analysed 1608 head and neck cancer (HNC) patients treated in a single centre. Time intervals were measured from the end of radiotherapy to the development of ORN and further analysed in the subgroups listed above. RESULTS: In all, 141 patients (8.8%) developed intra-oral ORN. Median time from radiotherapy to ORN development in the whole cohort was 9 months. Median interval for spontaneous ORN was 8 months, 6.5 months for intervention-related ORN, and 15 months for patients post-mandibulectomy. In patients who required dental extraction preradiotherapy, median interval of ORN onset was 5 months. CONCLUSION: In our study, a slightly higher proportion of patients with intervention developed ORN earlier in comparison with spontaneous ORN. The period from 12-18 months after radiotherapy was identified as having the highest probability of developing ORN in patients after mandibulectomy. A time for safer dental intervention after primary treatment was not identified.

Optimized target delineation procedure for the radiosurgery treatment of ventricular tachycardia: observer-independent accuracy.

Background: Part of the current stereotactic arrythmia radioablation (STAR) workflow is transfer of findings from the electroanatomic mapping (EAM) to computed tomography (CT). Here, we analyzed inter- and intraobserver variation in a modified EAM-CT registration using automatic registration algorithms designed to yield higher robustness. Materials and methods: This work is based on data of 10 patients who had previously undergone STAR. Two observers participated in this study: (1) an electrophysiologist technician (cardiology) with substatial experience in EAM-CT merge, and (2) a clinical engineer (radiotherapy) with minimum experience with EAM-CT merge. EAM-CT merge consists of 3 main steps: segmentation of left ventricle from CT (CT LV), registration of the CT LV and EAM, clinical target volume (CTV) delineation from EAM specific points. Mean Hausdorff distance (MHD), Dice Similarity Coefficient (DSC) and absolute difference in Center of Gravity (CoG) were used to assess intra/interobserver variability. Results: Intraobserver variability: The mean DSC and MHD for 3 CT LVs altogether was 0.92 ± 0.01 and 1.49 ± 0.23 mm. The mean DSC and MHD for 3 CTVs altogether was 0,82 ± 0,06 and 0,71 ± 0,22 mm. Interobserver variability: Segmented CT LVs showed great similarity (mean DSC of 0,91 ± 0,01, MHD of 1,86 ± 0,47 mm). The mean DSC comparing CTVs from both observers was 0,81 ± 0,11 and MHD was 0,87 ± 0,45 mm. Conclusions: The high interobserver similarity of segmented LVs and delineated CTVs confirmed the robustness of the proposed method. Even an inexperienced user can perform a precise EAM-CT merge following workflow instructions.

STereotactic Arrhythmia Radioablation (STAR): the Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary consortium (STOPSTORM.eu) and review of current patterns of STAR practice in Europe.

The EU Horizon 2020 Framework-funded Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary (STOPSTORM) consortium has been established as a large research network for investigating STereotactic Arrhythmia Radioablation (STAR) for ventricular tachycardia (VT). The aim is to provide a pooled treatment database to evaluate patterns of practice and outcomes of STAR and finally to harmonize STAR within Europe. The consortium comprises 31 clinical and research institutions. The project is divided into nine work packages (WPs): (i) observational cohort; (ii) standardization and harmonization of target delineation; (iii) harmonized prospective cohort; (iv) quality assurance (QA); (v) analysis and evaluation; (vi, ix) ethics and regulations; and (vii, viii) project coordination and dissemination. To provide a review of current clinical STAR practice in Europe, a comprehensive questionnaire was performed at project start. The STOPSTORM Institutions' experience in VT catheter ablation (83% ≥ 20 ann.) and stereotactic body radiotherapy (59% > 200 ann.) was adequate, and 84 STAR treatments were performed until project launch, while 8/22 centres already recruited VT patients in national clinical trials. The majority currently base their target definition on mapping during VT (96%) and/or pace mapping (75%), reduced voltage areas (63%), or late ventricular potentials (75%) during sinus rhythm. The majority currently apply a single-fraction dose of 25 Gy while planning techniques and dose prescription methods vary greatly. The current clinical STAR practice in the STOPSTORM consortium highlights potential areas of optimization and harmonization for substrate mapping, target delineation, motion management, dosimetry, and QA, which will be addressed in the various WPs.

Metastasising ameloblastoma or ameloblastic carcinoma? A case report with mutation analyses.

BACKGROUND: Ameloblastic carcinoma and metastasising ameloblastoma are rare epithelial odontogenic tumours with aggressive features. Distinguishing between these two lesions is often clinically difficult but necessary to predict tumour behaviour or to plan future therapy. Here, we provide a brief review of the literature available on these two types of lesions and present a new case report of a young man with an ameloblastoma displaying metastatic features. We also use this case to illustrate the similarities and differences between these two types of tumours and the difficulties of their differential diagnosis. CASE PRESENTATION: Our histopathological analyses uncovered a metastasising tumour with features of ameloblastic carcinoma, which developed from the ameloblastoma. We profiled the gene expression of Wnt pathway members in ameloblastoma sample of this patient, because multiple molecules of this pathway are involved in the establishing of cell polarity, cell migration or for epithelial-mesenchymal transition during tumour metastasis to evaluate features of tumor behaviour. Indeed, we found upregulation of several cell migration-related genes in our patient. Moreover, we uncovered somatic mutation BRAF p.V600E with known pathological role in cancerogenesis and germline heterozygous FANCA p.S858R mutation, whose interpretation in this context has not been discussed yet. CONCLUSIONS: In conclusion, we have uncovered a unique case of ameloblastic carcinoma associated with an alteration of Wnt signalling and the presence of BRAF mutation. Development of harmful state of our patient might be also supported by the germline mutation in one FANCA allele, however this has to be confirmed by further analyses.

HPV and RAD51 as Prognostic Factors for Survival in Inoperable Oral and Oropharyngeal Cancer in Patients Unfit for Chemotherapy Treated with Hyperfractionated Radiotherapy.

INTRODUCTION: The incidence of advanced oral cavity and oropharyngeal cancers is generally high. Treatment outcomes for patients, especially those unfit for comprehensive cancer treatment, are unsatisfactory. Therefore, the search for factors to predict response to treatment and increase overall survival is underway. OBJECTIVE: This study aimed to analyze the presence of 32 HPV genotypes in tumor samples of 34 patients and the effect of HPV status and RAD51 on overall survival. METHOD: Tumor samples of 34 patients with locally advanced oropharyngeal or oral cavity cancer treated with accelerated radiotherapy in monotherapy were analyzed using reverse hybridization and immunohistochemistry for the presence of HPV and RAD51. Its effect on overall survival was examined. RESULTS: Only two types of HPV were identified-HPV 16 (dominant) and HPV 66 (two samples). The HPV positivity was associated with a borderline insignificant improvement in 2-year (p = 0.083), 5-year (p = 0.159), and overall survival (p = 0.083). Similarly, the RAD51 overexpression was associated with borderline insignificant improvement in 2-year (p = 0.083) and 5-year (p = 0.159) survival. CONCLUSION: We found no statistically significant differences but detected trends toward improvement in the survival of HPV-positive and RAD51 overexpressing patients unfit for surgical treatment or chemotherapy treated with hyperfractionated radiotherapy. The trends, however, indicate that in a larger group of patients, the effects of these two parameters would likely be statistically significant.

Does Endoscopic Transnasal Optic Nerve Decompression Followed by Radiosurgery Improve Outcomes in the Treatment of Parasellar Meningiomas?

INTRODUCTION: The clinical management of parasellar meningiomas (PM) is challenging due to their intimate association with critical neurovascular structures. Consensus regarding the recommended treatment protocol is lacking. This study will evaluate patients' visual outcomes following endoscopic transnasal optic nerve decompression (ETOND) and will investigate the possibility of reducing the rate of complications associated with stereotactic radiosurgery (SRS). METHODS: Retrospective analysis was conducted on all patients who underwent ETOND for PM between 2013 and 2020. The study comprised 12 patients (7 women and 5 men aged 36-75 years; mean, 55.2 years; median, 57.6 years) in which 14 optic nerve decompression procedures were carried out. Patients were followed up for 6 to 86 months (mean, 29.3 months; median, 25 months). There were five cases of spheno-orbital meningioma, four cases of cavernous sinus meningioma, and one case each of petro-clival meningioma, optic nerve sheath meningioma, and planum sphenoidale/tuberculum sellae meningioma. Visual outcome was evaluated and any postoperative complications noted. RESULTS: Improvements in visual acuity were noted in 10 of 14 eyes (71.4%) 3 to 6 months postoperation. Visual acuity remained stable in the remaining four eyes. No deterioration of visual acuity was noted during the follow-up period. In total, 9 of the 12 patients underwent SRS. No tumor growth was determined, while reduction in tumor volume was noted in five patients following SRS. No complications associated with SRS or the surgical procedure were noted. CONCLUSIONS: ETOND appears to be a promising technique for increasing rates of improved visual function, while reducing the risk of post SRS-related complications. In combination with subsequent SRS, it is an ideal treatment modality in the management of parasellar meningiomas. Confirmation of our findings would require a larger, prospective multicenter study.

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

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

Accuracy of electroanatomical mapping-guided cardiac radiotherapy for ventricular tachycardia: pitfalls and solutions.

AIMS: To analyse and optimize the interobserver agreement for gross target volume (GTV) delineation on cardiac computed tomography (CCT) based on electroanatomical mapping (EAM) data acquired to guide radiotherapy for ventricular tachycardia (VT). METHODS AND RESULTS: Electroanatomical mapping data were exported and merged with the segmented CCT using manual registration by two observers. A GTV was created by both observers for predefined left ventricular (LV) areas based on preselected endocardial EAM points indicating a two-dimensional (2D) surface area of interest. The influence of (interobserver) registration accuracy and availability of EAM data on the final GTV and 2D surface location within each LV area was evaluated. The median distance between the CCT and EAM after registration was 2.7 mm, 95th percentile 6.2 mm for observer #1 and 3.0 mm, 95th percentile 7.6 mm for observer #2 (P = 0.9). Created GTVs were significantly different (8 vs. 19 mL) with lowest GTV overlap (35%) for lateral wall target areas. Similarly, the highest shift between 2D surfaces was observed for the septal LV (6.4 mm). The optimal surface registration accuracy (2.6 mm) and interobserver agreement (Δ interobserver EAM surface registration 1.3 mm) was achieved if at least three cardiac chambers were mapped, including high-quality endocardial LV EAM. CONCLUSION: Detailed EAM of at least three chambers allows for accurate co-registration of EAM data with CCT and high interobserver agreement to guide radiotherapy of VT. However, the substrate location should be taken in consideration when creating a treatment volume margin.

Real-time measurement of ICD lead motion during stereotactic body radiotherapy of ventricular tachycardia.

BACKGROUND: Here we aimed to evaluate the respiratory and cardiac-induced motion of a ICD lead used as surrogate in the heart during stereotactic body radiotherapy (SBRT) of ventricular tachycardia (VT). Data provides insight regarding motion and motion variations during treatment. MATERIALS AND METHODS: We analyzed the log files of surrogate motion during SBRT of ventricular tachycardia performed in 20 patients. Evaluated parameters included the ICD lead motion amplitudes; intrafraction amplitude variability; correlation error between the ICD lead and external markers; and margin expansion in the superior-inferior (SI), latero-lateral (LL), and anterior-posterior (AP) directions to cover 90% or 95% of all amplitudes. RESULTS: In the SI, LL, and AP directions, respectively, the mean motion amplitudes were 5.0 ± 2.6, 3.4. ± 1.9, and 3.1 ± 1.6 mm. The mean intrafraction amplitude variability was 2.6 ± 0.9, 1.9 ± 1.3, and 1.6 ± 0.8 mm in the SI, LL, and AP directions, respectively. The margins required to cover 95% of ICD lead motion amplitudes were 9.5, 6.7, and 5.5 mm in the SI, LL, and AP directions, respectively. The mean correlation error was 2.2 ± 0.9 mm. CONCLUSIONS: Data from online tracking indicated motion irregularities and correlation errors, necessitating an increased CTV-PTV margin of 3 mm. In 35% of cases, the motion variability exceeded 3 mm in one or more directions. We recommend verifying the correlation between CTV and surrogate individually for every patient, especially for targets with posterobasal localization where we observed the highest difference between the lead and CTV motion.

Osteolytic bone lesions, hypercalcemia and paraprotein, but not a myeloma: case report and review of literature.

In June 2018, 77-year-old man was referred to The Department of Haematooncology, University Hospital Ostrava, for suspicion of multiple myeloma. This was supported by laboratory findings of hypercalcemia, paraprotein IgA κ in serum and by the presence of multiple osteolytic skeletal lesions. Low number of plasma cells in bone marrow sample - cytologically (3.6 %) as well as in flow cytometry (less than 95 % clonal plasma cells out of total bone marrow plasma cells) - pointed at the direction of monoclonal gammopathy of undetermined significance (MGUS). In the course of differential diagnosis of hypercalcemia, elevated level of parathormone had been found which led to the performance of 99mTc-MIBI scintigraphy where parathyroid adenoma was discovered and later histologically verified. The final diagnosis was determined as a coincidence of MGUS and primary hyperparathyroidism. This case report also contains brief differential diagnosis of hypercalcemia and osteolytic skeletal lesions and suggestions for their diagnostic algorithms.

Stereotactic radiosurgery for ablation of ventricular tachycardia.

AIMS: Stereotactic body radiotherapy (SBRT) for ventricular tachycardias (VTs) could be an option after failed catheter ablation. In this study, we analysed the long-term efficacy and toxicity of SBRT applied as a bail-out procedure. METHODS AND RESULTS: Patients with structural heart disease and unsuccessful catheter ablations for VTs underwent SBRT. The planning target volume (PTV) was accurately delineated using exported 3D electroanatomical maps with the delineated critical part of re-entry circuits. This was defined by detailed electroanatomic mapping and by pacing manoeuvres during the procedure. Using the implantable cardioverter-defibrillator lead as a surrogate contrast marker for respiratory movement compensation, 25 Gy was delivered to the PTV using CyberKnife. We evaluated occurrences of sustained VT, electrical storm, antitachycardia pacing, and shock; time to death; and radiation-induced events. From 2014 until March 2017, 10 patients underwent radiosurgical ablation (mean PTV, 22.15 mL; treatment duration, 68 min). After radiosurgery, four patients experienced nausea and one patient presented gradual progression of mitral regurgitation. During the follow-up (median 28 months), VT burden was reduced by 87.5% compared with baseline (P = 0.012) and three patients suffered non-arrhythmic deaths. After the blanking period, VT recurred in eight of 10 patients. The mean time to first antitachycardia pacing and shock were 6.5 and 21 months, respectively. CONCLUSION: Stereotactic body radiotherapy appears to show long-term safety and effectiveness for VT ablation in structural heart disease inaccessible to catheter ablation. We report one possible radiation-related toxicity and promising overall survival, warranting evaluation in a prospective multicentre clinical trial.

Hyperfractionated stereotactic reirradiation for recurrent head and neck cancer.

PURPOSE: The goal of this work was to evaluate the efficacy and toxicity of hyperfractionated stereotactic reirradiation (re-RT) as a treatment for inoperable, recurrent, or second primary head and neck squamous cell cancer (HNSCC) that is not suitable for systemic treatment. PATIENTS AND MATERIALS: Forty patients with recurrent or second primary HNSCC were included in this study. The patients had a median gross tumor volume of 76 ml (range 14-193 ml) and a previous radiotherapy dose greater than 60 Gy. Treatment was designed to cover 95 % of the planning target volume (PTV, defined as gross tumor volume [GTV] + 3 mm to account for microscopic spreading, with no additional set-up margin) with the prescribed dose (48 Gy in 16 fractions b.i.d.). Treatment was administered twice daily with a minimum 6 h gap. Uninvolved lymph nodes were not irradiated. RESULTS: Treatment was completed as planned for all patients (with median duration of 11 days, range 9-14 days). Acute toxicity was evaluated using the RTOG/EORTC scale. A 37 % incidence of grade 3 mucositis was observed, with recovery time of ≤ 4 weeks for all of these patients. Acute skin toxicity was never observed to be higher than grade 2. Late toxicity was also evaluated according to the RTOG/EORTC scale. Mandible radionecrosis was seen in 4 cases (10 %); however, neither carotid blowout syndrome nor other grade 4 late toxicity occurred. One-year overall survival (OS) and local progression-free survival (L-PFS) were found to be 33 and 44 %, respectively. Performance status and GTV proved to be significant prognostic factors regarding local control and survival. CONCLUSION: Hyperfractionated stereotactic re-RT is a reasonable treatment option for patients with recurrent/second primary HNSCC who were previously exposed to high-dose irradiation and who are not candidates for systemic treatment or hypofractionation.

Monitoring of CRT-D devices during radiation therapy in vitro.

BACKGROUND: Using of active cardiac medical devices increases steadily. In Europe, there were 183 implants of ICD and 944 implants of PM, 119 of biventricular ICD and 41 of biventricular PM, all per million inhabitants in 2014. Healthcare environments, including radiotherapy treatment rooms, are considered challenging for these implantable devices. Exposure to radiation may cause the device to experience premature elective replacement indicator, decreased pacing amplitude or pacing inhibition, inappropriate shocks or inhibition of tachyarrhythmia therapy and loss of device function. These impacts may be temporary or permanent. The aim of this study was to evaluate the influence of linear accelerator ionizing radiation dose of 10 Gy on the activity of the biventricular cardioverter-defibrillator in different position in radiation beam. METHODS: Two identical wireless communication devices with all three leads were used for the measurement. Both systems were soused into solution saline and exposed in different position in the beam of linear accelerator per 10 Gy fractions. In comparison of usually used maximum recommended dose of 2 Gy, the radiation doses used in test were five times higher. Using the simultaneous monitoring wireless communication between device and its programmer allowed watching of the devices activities, noise occurrence or drop of biventricular pacing on the programmer screen, observed by local television loop camera. RESULTS: At any device position in radiation beam, there were no influences of the device activity at dose of 10 Gy neither a significant increase of a solution saline temperature in any of the measured positions of CRT-D systems in linear accelerator. CONCLUSIONS: The results of the study indicated, that the recommendation dose for treating the patients with implantable devices are too conservative and the risk of device failure is not so high. The systems can easily withstand the dose fractions of tens Gy, which would allow current single-dose-procedure treatment in radiation therapy. Even though the process of the random alteration of device memory and electrical components by scatter particles not allowed to specify a safe dose during ionizing radiation, this study showed that the safe limit are above the today used dose fractions.

A single reference measurement can predict liver tumor motion during respiration.

AIM: To evaluate liver tumor motion and how well reference measurement predicts motion during treatment. MATERIAL AND METHODS: This retrospective study included 20 patients with colorectal cancer that had metastasized to the liver who were treated with stereotactic ablative radiotherapy. An online respiratory tumor tracking system was used. Tumor motion amplitudes in the superior-inferior (SI), latero-lateral (LL), and anterior-posterior (AP) directions were collected to generate patient-specific margins. Reference margins were generated as the mean motion and 95th percentile of motion from measurements recorded for different lengths of time (1, 3, and 5 min). We analyzed the predictability of tumor motion in each axis, based on the reference measurement and intra-/interfraction motions. RESULTS: About 96,000 amplitudes were analyzed. The mean tumor motions were 9.9 ± 4.2 mm, 2.6 ± 0.8 mm, and 4.5 ± 1.8 mm in the SI, LL, and AP directions, respectively. The intrafraction variations were 3.5 ± 1.8 mm, 0.63 ± 0.35 mm, and 1.4 ± 0.65 mm for the SI, LL, and AP directions, respectively. The interfraction motion variations were 1.32 ± 0.79 mm, 0.31 ± 0.23 mm, and 0.68 ± 0.62 mm for the SI, LL, and AP directions, respectively. The Pearson's correlation coefficients for margins based on the reference measurement (mean motion or 95th percentile) and margins covering 95% of the motion during the whole treatment were 0.8-0.91, 0.57-0.7, and 0.77-0.82 in the SI, LL, and AP directions, respectively. CONCLUSION: Liver tumor motion in the SI direction can be adequately represented by the mean tumor motion amplitude generated from a single 1 min reference measurement. Longer reference measurements did not improve results for patients who were well-educated about the importance of regular breathing. Although the study was based on tumor tracking data, the results are useful for ITV delineation when tumor tracking is not available.

Is there an intermediate-risk non-seminoma? long-term treatment results from a single center.

PURPOSE: We retrospectively assessed the treatment results of patients with testicular non-seminoma to evaluate possible predictive and prognostic factors. METHODS: 189 patients with testicular non-seminoma treated between 2000 and 2012 were retrospectively evaluated. Treatment was based on orchiectomy plus chemotherapy (bleomycin/etoposide/cisplatin and vinblastine/ifosfamide/ cisplatin); retroperitoneal lymphadenectomy was only performed for residual disease after chemotherapy. The treatment protocol was updated regularly according to international standards. Overall survival (OS) was evaluated with the Kaplan-Meier method at a significance level of 5% according to stage, Karnofsky performance status (KPS), and chemotherapy dose intensity. RESULTS: OS differed significantly for patients at different TNM stages (p=0.000); however, detailed analysis revealed significantly worse survival only in stage IIIC (10-year OS for IIIC vs IIIA+B, 35 vs 88%, p=0.001), while the difference between IIIB and lower stages was not significant (p=0.383). Patients with no chemotherapy dose reduction had significantly higher OS than those with any kind of dose reduction (10-year OS 96 vs 0%, p=0.000). For stage IIIC disease, however, dose intensity had no influence on OS (p=0.167). KPS had no prognostic significance for OS (KPS<80 vs ≥80, p=0.627) for stage IIIA+B and for stage IIIC. CONCLUSION: The standard of care for testicular non-seminoma offers excellent prognosis with no significant differences in OS for good- and intermediate-risk patients. Reduction of chemotherapy dose negatively impacted OS in patients with stage IIIA+B and thus should be avoided.

Dosimetric comparison of MRI-based HDR brachytherapy and stereotactic radiotherapy in patients with advanced cervical cancer: A virtual brachytherapy study.

AIM: To evaluate the treatment plans of 3D image-guided brachytherapy (BT) and stereotactic robotic radiotherapy with online image guidance - CyberKnife (CK) in patients with locally advanced cervix cancer. METHODS AND MATERIALS: Ten pairs of plans for patients with locally advanced inoperable cervical cancer were created using MR based 3D brachytherapy and stereotaxis CK. The dose that covers 98% of the target volume (HR CTV D98) was taken as a reference and other parameters were compared. RESULTS: Of the ten studied cases, the dose from D100 GTV was comparable for both devices, on average, the BT GTV D90 was 10-20% higher than for CK. The HR CTV D90 was higher for CK with an average difference of 10-20%, but only fifteen percent of HR CTV (the peripheral part) received a higher dose from CK, while 85% of the target volume received higher doses from BT. We found a significant organ-sparing effect of CK compared to brachytherapy (20-30% lower doses in 0.1 cm(3), 1 cm(3), and 2 cm(3)). CONCLUSION: BT remains to be the best method for dose escalation. Due to the significant organ-sparing effect of CK, patients that are not candidates for BT could benefit from stereotaxis more than from classical external beam radiotherapy.

Hypertrophic obstructive cardiomyopathy with recurrent ventricular tachycardias: from catheter ablation and stereotactic radiotherapy to heart transplant-a case report.

Background: Management of hypertrophic obstructive cardiomyopathy (HOCM) is often challenging, depending on clinical manifestation. This case report illustrates the complex treatment of HOCM with associated recurrent ventricular arrhythmias. Case summary: A 54-year-old female with HOCM diagnosed in 2012 underwent a failed attempt for alcohol septal ablation, implantation of an implantable cardioverter-defibrillator, and repeated radiofrequency ablations (including ablation of the septal bulge to reduce LV obstruction). For ventricular tachycardia (VT) recurrences, she had stereotactic arrhythmia radioablation with subsequent epicardial cryoablation from mini-thoracotomy, and endocardial ablation with pulsed field energy. The situation was finally solved by mechanical support and heart transplantation. Discussion: A few important lessons can be learned from the case. First, radiofrequency ablation was used successfully to decrease left outflow tract obstruction. Second, stereotactic radiotherapy has been used after four previous endo/epicardial catheter ablations to decrease the recurrences of VT. Third, mini-thoracotomy was used after previous epicardial ablation with subsequent adhesions to modify the epicardial substrate with cryoenergy. Fourth, pulsed field ablation of atrial fibrillation resulted in an excellent therapeutic effect. Fifth, pulsed field ablation was also used to modify the substrate for VT, and was complicated by transient AV block with haemodynamic deterioration requiring mechanical support. Finally, a heart transplant was the ultimate solution in the management of recurrent VT.

Survival analysis after stereotactic ablative radiotherapy for early stage non-small cell lung cancer: a single-institution cohort study.

BACKGROUND: Stereotactic ablative radiotherapy (SABR) is the standard treatment for medically inoperable early-stage non-small cell lung cancer (ES-NSCLC), but which patients benefit from stereotactic radiotherapy is unclear. The aim of this study was to analyze prognostic factors for early mortality. METHODS: From August 2010 to 2022, 617 patients with medically inoperable, peripheral or central ES-NSCLC were treated with SABR at our institution. We retrospectively evaluated the data from 172 consecutive patients treated from 2018 to 2020 to analyze the prognostic factors associated with overall survival (OS). The biological effective dose was > 100 Gy10 in all patients, and 60 Gy was applied in 3-5 fractions for a gross tumor volume (GTV) + 3 mm margin when the tumor diameter was < 1 cm; 30-33 Gy was delivered in one fraction. Real-time tumor tracking or an internal target volume approach was applied in 96% and 4% of cases, respectively. In uni- and multivariate analysis, a Cox model was used for the following variables: ventilation parameter FEV1, histology, age, T stage, central vs. peripheral site, gender, pretreatment PET, biologically effective dose (BED), and age-adjusted Charlson comorbidity index (AACCI). RESULTS: The median OS was 35.3 months. In univariate analysis, no correlation was found between OS and ventilation parameters, histology, PET, or centrality. Tumor diameter, biological effective dose, gender, and AACCI met the criteria for inclusion in the multivariate analysis. The multivariate model showed that males (HR 1.51, 95% CI 1.01-2.28; p = 0.05) and AACCI > 5 (HR 1.56, 95% CI 1.06-2.31; p = 0.026) were significant negative prognostic factors of OS. However, the analysis of OS showed that the significant effect of AACCI > 5 was achieved only after 3 years (3-year OS 37% vs. 56%, p = 0.021), whereas the OS in one year was similar (1-year OS 83% vs. 86%, p = 0.58). CONCLUSION: SABR of ES-NSCLC with precise image guidance is feasible for all medically inoperable patients with reasonable performance status. Early deaths were rare in our real-life cohort, and OS is clearly higher than would have been expected after best supportive care.