Pancreatic SABR using peritumoral fiducials, triggered imaging and breath-hold.

Background: We aim to present our linear accelerator-based workflow for pancreatic stereotactic ablative radiotherapy (SABR) in order to address the following issues: intrafractional organ motion management, Cone Beam CT (CBCT) image quality, residual errors with dosimetric consequences, treatment time, and clinical results. Methods: Between 2016 and 2021, 14 patients with locally advanced pancreatic cancer were treated with induction chemotherapy and SABR using volumetric modulated arc therapy (VMAT). Internal target volume (ITV) concept (5), phase-gated (4), or breath hold (5) techniques were used. Treatment was verified by CBCT before and after irradiation, while tumor motion was monitored and controlled by kV triggered imaging and beam hold using peritumoral surgical clips. Beam interruptions and treatment time were recorded. The CBCT image quality was scored and supplemented by an agreement analysis (Krippendorff's-α) of breath-hold CBCT images to determine the position of OARs relative to the planning risk volumes (PRV). Residual errors and their dosimetry impact were also calculated. Progression free (PFS) and overall survival (OS) were assessed by the Kaplan-Meier analysis with acute and late toxicity reporting (CTCAEv4). Results: On average, beams were interrupted once (range: 0-3) per treatment session on triggered imaging. The total median treatment time was 16.7 ± 10.8 min, significantly less for breath-hold vs. phase-gated sessions (18.8 ± 6.2 vs. 26.5 ± 13.4, p < 0.001). The best image quality was achieved by breath hold CBCT. The Krippendorff's-α test showed a strong agreement among five radiation therapists (mean K-α value: 0.8 (97.5%). The mean residual errors were <0.2 cm in each direction resulting in an average difference of <2% in dosimetry for OAR and target volume. Two patients received offline adaptation. The median OS/PFS after induction chemotherapy and SABR was 20/12 months and 15/8 months. No Gr. ≥2 acute/late RT-related toxicity was noted. Conclusion: Linear accelerator based pancreatic SABR with the combination of CBCT and triggered imaging + beam hold is feasible. Peritumoral fiducials improve utility while breath-hold CBCT provides the best image quality at a reasonable treatment time with offline adaptation possibilities. In well-selected cases, it can be an effective alternative in clinics where CBCT/MRI-guided online adaptive workflow is not available.

Improved survival of non-small cell lung cancer patients after introducing patient navigation: A retrospective cohort study with propensity score weighted historic control.

OnkoNetwork is a patient navigation program established in the Moritz Kaposi General Hospital to improve the timeliness and completeness of cancer investigations and treatment. The H2020 SELFIE consortium selected OnkoNetwork as a promising integrated care initiative in Hungary and conducted a multicriteria decision analysis based on health, patient experience, and cost outcomes. In this paper, a more detailed analysis of clinical impacts is provided in the largest subgroup, non-small cell lung cancer (NSCLC) patients. A retrospective cohort study was conducted, enrolling new cancer suspect patients with subsequently confirmed NSCLC in two annual periods, before and after OnkoNetwork implementation (control and intervention cohorts, respectively). To control for selection bias and confounding, baseline balance was improved via propensity score weighting. Overall survival was analyzed in univariate and multivariate weighted Cox regression models and the effect was further characterized in a counterfactual analysis. Our analysis included 123 intervention and 173 control NSCLC patients from early to advanced stage, with significant between-cohort baseline differences. The propensity score-based weighting resulted in good baseline balance. A large survival benefit was observed in the intervention cohort, and intervention was an independent predictor of longer survival in a multivariate analysis when all baseline characteristics were included (HR = 0.63, p = 0.039). When post-baseline variables were included in the model, belonging to the intervention cohort was not an independent predictor of survival, but the survival benefit was explained by slightly better stage distribution and ECOG status at treatment initiation, together with trends for broader use of PET-CT and higher resectability rate. In conclusion, patient navigation is a valuable tool to improve cancer outcomes by facilitating more timely and complete cancer diagnostics. Contradictory evidence in the literature may be explained by common sources of bias, including the wait-time paradox and adjustment to intermediate outcomes.

Predictive value of PET/CT based metabolic information in the modern 3D based radiotherapy treatment of head and neck can-cer patients - single institute study.

OBJECTIVE: The aim of the study was to evaluate the predictive value of pretreatment positron emission tomography (PET) standardized uptake value (SUVmax), standardized uptake value corrected for lean body mass (SULpeak) value, metabolic tumour volume (MTV) and total lesion glycolysis (TLG) parameters of the primary tumour assessed with PET/computed tomography (CT) in the clinical out-come in patients diagnosed with histopathologically confirmed head and neck squamous cell carcinoma. MATERIALS AND METHODS: Retrospective evaluation was performed using PET/CT image datasets of 52 histologically proven head and neck cancer patients in 4 weeks' prior receiving definitive chemo-radiotherapy (CRT). Positron emission tomography /CT was performed before the CRT and 12 weeks after it for response evaluation. Image data was used for target volume delineation and for specify SUVmax, SULpeak, MTV and TLG parameters of the primary tumour. According to the results of the therapeutic response evaluation two patient subgroups were created in relation to the presence or absence of viable tumour. Metabolic data from pre-treatment PET/CT and therapeutic response were correlated using Kruskal-Wallis test. RESULTS: After completion of the CRT in 24/52 (46%) cases viable residual tumour was detected on restaging PET/CT, while in 28/52 (54%) patients showed complete remission. For the therapeutic success prediction assessment, we could not find any significant correlation with pre-treatment SUVmax and SULpeak values (P>0.44, P>0.33). Total lesion glycolysis provided nearly significant difference (P=0.052) and MTV had shown significant difference (P=0.001) between the two patient subgroups statistically. CONCLUSION: Simple metabolic data (SUVmax and SULpeak) from pretreatment fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT were unable to predict therapeutic response, while volumetric information containing MTV and TLG parameters proved to be more useful, thus their inclusion to risk stratification may also have additional value.

Benefits Of Timely Care In Pancreatic Cancer: A Systematic Review To Navigate Through The Contradictory Evidence.

The evidence base of policies that improve the timeliness of cancer care is under ongoing debate. Pancreatic cancer is frequently diagnosed in a stage when curative therapy is not feasible; hence, it is an important target for timelier healthcare interventions. The objectives of our research were to identify all clinical studies on pancreatic cancer care delays via a systematic literature review, to assess the study methodologies for possible biases, to conclude on the available evidence, and to formulate research recommendations on evidence gaps. Nineteen studies were identified and eight reported multivariate analyses. Although many sources of bias shifted the results towards negative or paradoxical findings, a statistically significant association of shorter delays with better clinical outcomes was demonstrated in the majority of studies reporting multivariate analyses. Noninferiority analyses were not published. Further efforts to provide timely care for pancreatic cancer patients are encouraged, and studies on the associations of delay with patient experience and healthcare resource utilization are warranted.

[F-DOPA PET/MR based target definiton in the 3D based radiotherapy treatment of glioblastoma multiforme patients. First Hungarian experiences]. / F-DOPA-jelzett PET/CT-PET/MR alapú modern 3D besugárzástervezés glioblastoma multiformés (GBM-) betegek komplex kezelésében. Az elso magyarországi tapasztalatok.

BACKGROUND AND PURPOSE: Radiotherapy plays important role in the complex oncological treatment of glioblastoma multiforme (GBM). The modern 3D radiotherapy treatments are based on cross-sectional CT and MR information, however more attention is being paid to functional hybrid imaging describing the biological and functional morphology of tumor lesions. 18F-DOPA is an amino acid tracer with high specificity and sensitivity, which may play an important role in the precise definition of target volume in the irradiation process of GBM patients. Our study presents the first experiences with 18F-DOPA based PET/CT/MR 3D irradiation planning process. METHODS: In Hungary the 18F-DOPA radiotracer has been available for clinical use since September 2017. Between September 2017 and January 2018, at the Somogy County Kaposi Mór Teaching Hospital Dr. József Baka Diagnostic, Radiation Oncology, Research and Teaching Center 3 histologically verified glioblastoma multiforme patients received 18F-DOPA based 3D irradiation treatment. In the contouring process the native planning CT scanes were fused with the PET/MR series (T1 contrast enhanced, T2 and 18F-DOPA sequences). We defined 18F-DOPA uptake volume (BTV-F-DOPA), the T1 contrast enhanced MRI volume (GTV-T1CE), and the volume of the area covered by oedema on the T2 weighted MRI scan (CTV-oedema) in all patients. We also registered the BTV-F-DOPA volumes not covered by the conventional MR based target volumes. RESULTS: Examining the 3 cases, the average volume of 18F-DOPA tumor was 22.7 cm3 (range 15.3-30.9; SD = 7.82). The average GTV T1 CE was found to be 8.7 cm3 (range 3.8-13.2; SD = 4.70). The mean CTV oedema volume was 40.3 cm3 (range 27.7-57.7; SD = 15.36). A non-overlapping target volume difference (BTV-F-DOPA not covered by CTV oedema area) was 4.5 cm3 (range 1-10.3; SD = 5.05) for PTV definition. CONCLUSION: Based on our results the tumor area defined by the amino acid tracer is not fully identical with the MRI defined T2 oedema CTV. 18F-DOPA defined BTV can modify the definiton of the PTV, and the radiotherapy treatment.

Planning, implementation and operation of a personalized patient management system for subjects with first suspect of cancer (OnkoNetwork): system description based on a qualitative study.

BACKGROUND: OnkoNetwork is a recently established integrated care model with a personalized pathway system to manage patients with first suspect of a solid tumour in secondary care, that evolved as a regional initiative in Hungary. The primary aim of OnkoNetwork is the improvement of clinical outcomes via timely access to quality assured and defragmented healthcare services. The Horizon 2020 funded SELFIE project has selected OnkoNetwork for in-depth qualitative and quantitative evaluation. The aim of this study was to provide a qualitative evaluation of OnkoNetwork along the six components of the SELFIE conceptual framework: 1) service delivery, 2) leadership and governance, 3) workforce, 4) financing, 5) technologies and medical products, and 6) information and research. METHODS: Analysis of published and grey programme documentation, followed by 20 semi-structured interviews with representatives of programme initiators, general and financial managers, involved physicians and non-physician professionals, patients and their informal caregivers. Transcripts of all interviews were analysed by Mayring's content analysis method by two independent researchers. RESULTS: This study yielded the first comprehensive description of the programme. OnkoNetwork is a blue dahila in Central and Eastern Europe, providing timely and quality-assured healthcare services for the target patients by personalized patient path monitoring and management in a financially sustainable manner without macro-level financing of its operation. Innovative professional roles were implemented for non-physicians and physicians, and a supporting information technology application was developed. CONCLUSIONS: This paper provides a systematic description of OnkoNetwork on the six components of the SELFIE conceptual framework for integrated care in multimorbidity to understand how and why OnkoNetwork was implemented and cares (better) for its patients. Because integrated care models are designed and adjusted to their specific local needs and context, those few successful and sustainable models that were established in Central and Eastern European countries represent important benchmarks for other initiatives in this region. Experience with OnkoNetwork during its planning, implementation and operation including the description of key success factors and barriers as perceived by various stakeholder groups, may support the development of further integrated care models especially in countries with similar economic status and healthcare settings.

[The predictive role of PET/CT imaging in clinical N and M staging and treatment decision process. Institutional experiences in Hungary]. / A PET/CT szerepe a sugárkezelésre kerülo betegek N és M klinikai stagingjében, a terápia meghatározásában. Intézeti tapasztalatok.

INTRODUCTION AND AIM: The aim of our study was to investigate changes in clinical staging N (lymph node) and M (distant metastasis) in patients who receive PET/CT-based 3D radiotherapy within complex oncological treatment, and compare to conventional cross-sectional imaging staging technique. We also investigated the presence of PET/CT-detected second tumors and the effect of PET/CT on therapeutic decisions. METHOD: From the 1st of January 2015 to the 30th of November 2016, 192 patients (n = 192) were treated with PET/CT-based radiation (109 head, 44 lung, 28 rectum and 11 cervical localization) in the Oncoradiology Institute of the Health Center of the University of Kaposvár. All patients received conventional cross-sectional and PET/CT imaging in accordance with the valid investigation protocol. The average time interval between the two cross-sectional investigations was 5.2 weeks. Clinical N and M staging was performed on the basis of the classification of the American Joint Committee on Cancer (AJCC) and the Union of International Cancer Control (UICC). RESULTS: By analyzing the clinical stages N and M separately, based on the results of the PET/CT studies, the N stage was changed in 77 cases and the M stage changed in 31 cases. Overall, the PET/CT study resulted in higher clinical stages in 68 (35.4%) patients and lower clinical stages in 14 (7.3%) patients. The treatment plan was changed in 9% of the patients (n = 18) (definitive versus palliative treatment) and the extension of radiotherapy treatment target volume (PTV) was indicated in 20% of the patients (n = 39) due to the change in clinical lymph node status. PET/CT also detected secondary tumors in 15 (8%) patients. CONCLUSION: Based on our results, the addition of PET/CT to conventional cross-sectional staging imaging permits a more accurate clinical classification of N and M stages and significantly influences therapeutic decisions. PET/CT imaging also provides a great help in detecting occult second tumors. The results of our Institute harmonize with the international data available in the literature. Orv Hetil. 2018; 159(39): 1593-1601.

[Hungarian clinical application opportunities of PET/MR imaging and first experiences]. / A PET/MR képalkotás magyarországi klinikai alkalmazásának lehetoségei, elso tapasztalatai.

Hungary's first and still only multimodality PET/MR device is operating in the Health Center of Kaposvár University. The aim of our review article is to present the current Hungarian PET/MR imaging application opportunities, our available initial experiences with this novel multimodality imaging technique in malignant and non-malignant diseases and further potential targeted clinical fields of use are also addressed. Orv Hetil. 2018; 159(34): 1375-1384.

Long-term follow-up results of concomitant chemoradiotherapy followed by adjuvant temozolomide therapy for glioblastoma multiforme patients. The importance of MRI information in survival: Single-center experience.

BACKGROUND AND PURPOSE: Glioblastoma multiforme (GBM) is the most common malignant primary anomaly of central nervous system. The GBM infiltrates the nearly sturctures from the initial tumor and its metastatic attribution is well known. The aim of our single-centered retrospective study was to introduce the importance of postoperative medical imaging confirmation of total tumor resection for patient with GBM combined concomitant and adjuvant chemoradiotherapy on a 10 year long patient follow up. METHODS: From January 2006 to April 2015 we registered 59 patients with newly diagnosed GBM at the University of Kaposvár Health Center Institute of Diagnostic Imaging and Radiation Oncology. The histological diagnosis was confirmed by a proficient neuropathologist (World Health Organisation WHO; grade IV astrocytoma). According to histological status if the ECOG performance status of patients allowed it the mutidisciplinary oncoteam recommended adjuvant chemoradiotherapy all features strictly by Stupp protocol. (60 Gy dose on the gross tumor volume and 2-3 cm margin for the clinical target volume with parallel 75 mg/m2 TMZ. Four weeks after monotherapial phase patients had to recieve 6 cycles of TMZ first cycle with 150 mg/m2 up to 200 mg/m2). The irradiation was carried out by a conformal three dimensional planning system. RESULTS: 59 patients with the median age of 63 (range 17-84) year. Our sample counted 34 male patients and 25 woman patients. 14 patients underwent gross total tumor resection while, 39 patients underwent partial resection and the rest from our sample 6 patients passed through biopsy. Statistical analysis showed a lengthier survival among males than females, with a median survival of 13 months for males and females, the OS of 26.209 for males, meanwhile 15.625 for females. However, the difference is not considerable (log-rank p=0.203). Our study found that the estimated survival of patients at least 50 years old is significantly shorter at a median survival of 12 months (log rank p=0.027) than that of patients below 50 years of age at a median survival of 23 months. The longest estimated median survival was calculated with patients of ECOG '0' condition (16 months). However, no significant difference was found in the estimated survival of patients of different ECOG conditions (log-rank p=0.146). Based on the extent of surgery, complete resection resulted in the longest average survival of 36.4 months, followed by 21.5 months among patients with biopsy, and 15.8 months among patients with partial resection. Different surgical procedures, however, did not result in significant differences in survival (log-rank p=0.059). The overal survival of patients who had complete resection confirmed by MRI compared with the overal survival of patients with residual tumor confirmed by MRI as well we can estimate that there is significant difference between these two groups (p=0,004). CONCLUSION: Despite complex and intense treatment, recurrence is inevitable and causes relatively rapid death. In our analysis complete resection, as defined from the neurosurgeon's report and postoperative MRI, resulted in an independently significant improvement in OS. Our results are the evidences that the treatment of patients with glioblastoma multiforme in Hungary is at least on the same level as any other developed European countries.

[Pacemaker in MR: absolute contraindication?]. / Pacemaker az MR-ben: abszolút kontraindikáció?

Due to developments in pacemaker technology, implanted pacemakers do not mean an absolute contraindication for MRI examination. However, there are several aspects of MRI examinations that should be considered for safety reasons in pacemaker patients. Based on literature data and own experiments, the safety protocol of MRI examination in pacemaker-implanted patients is described. The interaction of pacemakers--frequently implanted in Hungary--with MR scanners of 0,35 and 1,5 T was studied in vitro. In addition, the cardiac MRI examination of two pacemaker patients is presented. -ICD pacemakers showed strong interaction with static and changing magnetic field that affected pacemaker performance significantly. MRI examination can be safely performed in pacemaker-independent patients. Based on our in vitro and in vivo measurements, MRI examination is still contraindicated in pacemaker-dependent patients. In pacemaker-independent patients blood pressure, ECG monitoring and pulsoximetry are absolutely necessary, in addition, equipment for resuscitation should be available. Pacemaker should be specifically programmed before MRI examination and parameters and functionality should be checked in details afterwards.