Corrigendum: Systemic treatment of breast cancer. 1st Central-Eastern European professional Consensus Statement on breast cancer.

[This corrects the article DOI: 10.3389/pore.2022.1610383.].

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.

[Multicentric Hungarian results of cabozantinib therapy in patients with metastatic kidney cancer based on real-world data]. / Áttétes vesedaganatos betegek kabozantinibterápiájának multicentrikus magyarországi eredményei.

The aim of our analysis was to evaluate the efficacy of cabozantinib in patients with metastatic renal cell carcinoma. Cabozantinib therapy initiated between 01/01/2019 and 31/12/2022 was evaluated based on a retrospective review of data from 14 renal centers in Hungary. The starting dose was 60 or 40 mg. Physical examinations and laboratory tests were performed every 4 weeks and imaging studies 3-monthly. Tumor response was assessed according to RECIST 1.1, and toxicity according to NCI CTCAE 4.0. A total of 230 patient records were evaluated, 201 (87.4%) of them had clear cell RCC. Cabozantinib was administered as third, second and first-line treatment in 48.7%, 38.3% and <5% of cases, respectively. Dose reductions occurred in 62.6% and treatment interruption in 6.5%. Duration of therapy was 10.03 months, which was independent of dose reduction. Overall tumor response rate was 39.2% and clinical benefit was 82.8%. The duration of first-, second-, third- and fourth-line treatment was 11.47, 8.03, 11.57 and 10.13 months, respectively. Overall survival from the start of therapy was 22.0 months. Cabozantinib therapy in daily practice was more beneficial than according to registry study results. Dose reduction did not affect efficacy.

[Multicentric Hungarian results of cabozantinib therapy in patients with metastatic kidney cancer based on real-world data]. / Áttétes vesedaganatos betegek kabozantinibterápiájának multicentrikus magyarországi eredményei.

The aim of our analysis was to evaluate the efficacy of cabozantinib in patients with metastatic renal cell carcinoma. Cabozantinib therapy initiated between 01/01/2019 and 31/12/2022 was evaluated based on a retrospective review of data from 14 renal centers in Hungary. The starting dose was 60 or 40 mg. Physical examinations and laboratory tests were performed every 4 weeks and imaging studies 3-monthly. Tumor response was assessed according to RECIST 1.1, and toxicity according to NCI CTCAE 4.0. A total of 230 patient records were evaluated, 201 (87.4%) of them had clear cell RCC. Cabozantinib was administered as third, second and first-line treatment in 48.7%, 38.3% and <5% of cases, respectively. Dose reductions occurred in 62.6% and treatment interruption in 6.5%. Duration of therapy was 10.03 months, which was independent of dose reduction. Overall tumor response rate was 39.2% and clinical benefit was 82.8%. The duration of first-, second-, third- and fourth-line treatment was 11.47, 8.03, 11.57 and 10.13 months, respectively. Overall survival from the start of therapy was 22.0 months. Cabozantinib therapy in daily practice was more beneficial than according to registry study results. Dose reduction did not affect efficacy.

Hazai tapasztalatok metasztatikus kolorektális karcinóma bevacizumabbal kiegészített indukciós kemoterápiás kezelésével (AVACONT vizsgálat).

The primary aim of AVACONT was to collect data in the course of routine oncological care from patients with metastatic colorectal cancer (mCRC) treated with bevacizumab supplemented fluoropyrimidine-based chemotherapy doublet in an open, multicentre, observational study in Hungary. Primary endpoint of the study was to determine progression-free survival (PFS). The Full Analysis Set (FAS) comprised 280 patients. Median PFS calculated from enrolment was 270 days in the FAS population. The metastatic involvement of the liver or more than one organ significantly decreased (250 and 245 days), while a clinical response achieved significantly increased (partial response: 404, complete response: 623 days) the mPFS calculated from enrolment. PFS calculated from the start of the first-line treatment was significantly decreased by the presence of mutant RAS gene (481 vs. 395 days). The results confirm the efficacy, known prognostic factors and safety profile of bevacizumab in combination with chemotherapy dosed during standard oncology care in Hungarian centres.

Systemic Treatment of Breast Cancer. 1st Central-Eastern European Professional Consensus Statement on Breast Cancer.

This text is based on the recommendations accepted by the 4th Hungarian Consensus Conference on Breast Cancer, modified based on the international consultation and conference within the frames of the Central-Eastern European Academy of Oncology. The professional guideline primarily reflects the resolutions and recommendations of the current ESMO, NCCN and ABC5, as well as that of the St. Gallen Consensus Conference statements. The recommendations cover classical prognostic factors and certain multigene tests, which play an important role in therapeutic decision-making. From a didactic point of view, the text first addresses early and then locally advanced breast cancer, followed by locoregionally recurrent and metastatic breast cancer. Within these, we discuss each group according to the available therapeutic options. At the end of the recommendations, we summarize the criteria for treatment in certain rare clinical situations.

Pathologic Complete Response Rates After Neoadjuvant Pertuzumab and Trastuzumab with Chemotherapy in Early Stage HER2-Positive Breast Cancer - Increasing Rates of Breast Conserving Surgery: A Real-World Experience.

Purpose: The neoadjuvant use of pertuzumab and trastuzumab with chemotherapy improves the pathologic complete response (pCR) in early HER2+ breast cancer. The aim of this study was to determine the pCR rate obtained with dual HER2 blockade in routine clinical practice. The secondary and tertiary objective was to investigate the impact of neoadjuvant systemic therapy (NST) on performing breast-conserving surgery and survival data. Methods: This was a multicentre, retrospective, observational study in patients with stage II and III HER2+ early breast cancer who received pertuzumab and trastuzumab-based NST. Data were collected from patients' medical records. Results: Eighty-two patients were included in the study treated in 8 cancer centers in Hungary between March 2015 and January 2020. The study included women with a median age of 50.3 years. The majority of the patients (95%) received a sequence of anthracycline-based chemotherapy followed by docetaxel. pCR was achieved in 54% of the cases. As a result of NST a significant increase of conservative breast surgeries (33% vs. 3.6% planned, p = 0.0001) was observed. Ki67 expression and neutrophil-to-lymphocyte ratio (NLR) significantly predicted pCR. None of the variables were independent predictors of DFS. Conclusion: The pCR rate achieved in our study demonstrates the reproducibility of trial data in a real-world population. The rate of breast-conserving surgery was significantly increased.

[Linac-based stereotactic ablative radiotherapy for pancreatic cancer with intrafractional triggered imaging]. / Hasnyálmirigyrák lineáris gyorsító alapú sztereotaxiás sugárterápiája kezelés alatti tumorkövetéssel.

Our aim was to present different treatment strategies (non-gated [NG], respiratory-gated [RG] and deep inspiration breath-hold [DIBH] technique) of linac-based stereotaxic ablative radiotherapy (SABR) for pancreatic cancer in terms of use of marker, abdominal compression, image quality, and time efficiency. From October 2016 to October 2020 14 patients were treated with VMAT-based SABR (NG: 6/14, 8/14 RG RT including 3/8 DIBH SABR). Treatment verification consisted of 3D/4D CBCTs. For intrafractional tumor visualization (11/14) different type of fiducials were used. The average treatment time was the shortest with NG RT, followed by DIBH and RG RT. However, the best image quality was achieved with DIBH technique. The Krippendorff's agreement test among three independent RTTs showed that DIBH CBCT (Cone Beam CT) can produce sufficient image quality for OARs and can be used to reliably determine OARs position related to safety zone (PRV). Overall, marker-based DIBH SABR with intrafractional tumor visualization appears to be the best technique on linac at present.

[Systemic treatment of breast cancer: professional guideline]. / Az emlorák szisztémás kezelése: szakmai irányelvek.

Since the III. Breast Cancer Consensus Conference, a number of new evidence based on clinical trial results have been published which justified updating the 2016 recommendation. In addition to classical prognostic factors, some multigenic tests, which we have incorporated into the recommendation, will play an important role in therapeutic decision-making. The professional guide primarily reflects the resolutions and recommendations of the current ESMO, NCCN, ABC4, as well as the St. Gallen Consensus Conference. From a didactic point of view, the text follows first the line of early and then locally advanced breast cancer, locoregionally recurrent and metastatic breast cancer. Within these, we discuss each group according to therapeutic options.

Fulvestrant Plus Vistusertib vs Fulvestrant Plus Everolimus vs Fulvestrant Alone for Women With Hormone Receptor-Positive Metastatic Breast Cancer: The MANTA Phase 2 Randomized Clinical Trial.

IMPORTANCE: Randomized clinical trials have demonstrated a substantial benefit of adding everolimus to endocrine therapy. Everolimus inhibits the mammalian target of rapamycin complex 1 (mTORC1) complex but not mTORC2, which can set off an activating feedback loop via mTORC2. Vistusertib, a dual inhibitor of mTORC1 and mTORC2, has demonstrated broad activity in preclinical breast cancer models, showing superior activity to everolimus. OBJECTIVE: To evaluate the safety and efficacy of vistusertib in combination with fulvestrant compared with fulvestrant alone or fulvestrant plus everolimus in postmenopausal women with estrogen receptor-positive advanced or metastatic breast cancer. DESIGN, SETTING, AND PARTICIPANTS: The MANTA trial is an open-label, phase 2 randomized clinical trial in which 333 patients with estrogen receptor-positive breast cancer progressing after prior aromatase inhibitor treatment underwent randomization (2:3:3:2) between April 1, 2014, and October 24, 2016, at 88 sites in 9 countries: 67 patients were assigned to receive fulvestrant, 103 fulvestrant plus vistusertib daily, 98 fulvestrant plus vistusertib intermittently, and 65 fulvestrant plus everolimus. Treatment was continued until disease progression, development of unacceptable toxic effects, or withdrawal of consent. Analysis was performed on an intention-to-treat basis. INTERVENTIONS: Fulvestrant alone or in combination with vistusertib (continuous or intermittent dosing schedules) or everolimus. MAIN OUTCOMES AND MEASURES: The primary end point was progression-free survival (PFS). RESULTS: Among the 333 women in the study (median age, 63 years [range, 56-70 years]), median PFS was 5.4 months (95% CI, 3.5-9.2 months) with fulvestrant, 7.6 months (95% CI, 5.9-9.4 months) with fulvestrant plus daily vistusertib, 8.0 months (95% CI, 5.6-9.9 months) with fulvestrant plus intermittent vistusertib, and 12.3 months (95% CI, 7.7-15.7 months) with fulvestrant plus everolimus. There was no significant difference in PFS between those receiving fulvestrant plus daily or intermittent vistusertib and fulvestrant alone (hazard ratio, 0.88 [95% CI, 0.63-1.24]; P = .46; and hazard ratio, 0.79 [95% CI, 0.55-1.12]; P = .16). CONCLUSIONS AND RELEVANCE: The combination of fulvestrant plus everolimus demonstrated significantly longer PFS compared with fulvestrant plus vistusertib or fulvestrant alone. The trial failed to demonstrate a benefit of adding the dual mTORC1 and mTORC2 inhibitor vistusertib to fulvestrant. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02216786 and EudraCT number: 2013-002403-34.

Capecitabine in Combination with Docetaxel in First Line in HER2-Negative Metastatic Breast Cancer: an Observational Study.

Due to the limited experience with capecitabine plus docetaxel (XT) combination in the first-line treatment of metastatic breast cancer in Hungary, the main objective of the study was to analyze the effectiveness and tolerability of XT therapy. A prospective, open-label, non-randomized, single-arm, multicenter, observational study was designed. All female patients were eligible whose metastatic breast cancer could be treated with the XT protocol according to the summary of product characteristics of the drugs. The median progression free survival was 9.9 ± 3.0 months. Time to treatment failure was 4.6 ± 5.1 months on average. The overall response rate was 28.9 %, the clinical benefit rate was 73.3 %. The treatment was discontinued in 35.6 % of patients due to disease progression and in 20.0 % due to adverse events (AE). 33 patients with a total of 73 AEs have been reported, and 13 of them had serious adverse events (SAE). The efficacy and the safety profile of XT chemotherapy proven in the study are consistent with the results demonstrated in randomized trials. First-line XT chemotherapy effectively improves the PFS in metastatic breast cancer.