BACKGROUND: In the two European Union (EU)-funded projects, PCM4EU (Personalized Cancer Medicine for all EU citizens) and PRIME-ROSE (Precision Cancer Medicine Repurposing System Using Pragmatic Clinical Trials), we aim to facilitate implementation of precision cancer medicine (PCM) in Europe by leveraging the experience from ongoing national initiatives that have already been particularly successful. PATIENTS AND METHODS: PCM4EU and PRIME-ROSE gather 17 and 24 partners, respectively, from 19 European countries. The projects are based on a network of Drug Rediscovery Protocol (DRUP)-like clinical trials that are currently ongoing or soon to start in 11 different countries, and with more trials expected to be established soon. The main aims of both the projects are to improve implementation pathways from molecular diagnostics to treatment, and reimbursement of diagnostics and tumour-tailored therapies to provide examples of best practices for PCM in Europe. RESULTS: PCM4EU and PRIME-ROSE were launched in January and July 2023, respectively. Educational materials, including a podcast series, are already available from the PCM4EU website (http://www.pcm4eu.eu). The first reports, including an overview of requirements for the reimbursement systems in participating countries and a guide on patient involvement, are expected to be published in 2024. CONCLUSION: PCM4EU and PRIME-ROSE were launched in January and July 2023, respectively. Educational materials, including a podcast series, are already available from the PCM4EU website (http://www.pcm4eu.eu). The first reports, including an overview of requirements for the reimbursement systems in participating countries and a guide on patient involvement, are expected to be published in 2024. CONCLUSION: European collaboration can facilitate the implementation of PCM and thereby provide affordable and equitable access to precision diagnostics and matched therapies for more patients.

• MeSH
• Evropská unie MeSH
• individualizovaná medicína * metody   MeSH
• klinické zkoušky jako téma organizace a řízení   MeSH
• lidé MeSH
• nádory * terapie   MeSH
• přehodnocení terapeutických indikací léčivého přípravku MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH

• MeSH
• akutní myeloidní leukemie * epidemiologie   terapie   MeSH
• lidé MeSH
• registrace MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH

INTRODUCTION: BCR-ABL1-like acute lymphoblastic leukemia (ALL) is a high-risk disease with a complex genomic background. Though extensively studied, data on the frequency and mutual associations of present mutations are still incomplete in adult patients. This retrospective study aims to map the genomic landscape of B-other ALL in a cohort of adult patients with a focus on the BCR-ABL1-like ALL subtype. METHODS: We analyzed bone marrow and peripheral blood samples of adult B-other ALL patients treated consecutively at three major Czech teaching hospitals. Samples were analyzed by cytogenetic methods, gene expression profiling, multiplex ligation-dependent probe amplification (MLPA), and next-generation sequencing (NGS). RESULTS: Fifty-eight B-other ALL patients (not BCR-ABL1, KMT2A-rearranged, ETV6-RUNX1, TCF3-PBX1, or iAMP21) were included in the study. Median follow-up was 23.8 months. Samples from 33 patients were available for a gene expression analysis, 48.9% identified as BCR-ABL1-like ALL. Of the BCR-ABL1-like ALL cases, 18.8% harbored IGH-CRLF2 and 12.5% P2RY8-CRLF2 fusion gene. We observed a higher MRD failure rate in BCR-ABL1-like than in non-BCR-ABL1-like ALL patients after the induction treatment (50.0 vs. 13.3%, p=.05). There was a trend to worse progression-free and overall survival in the BCR-ABL1-like group, though not statistically significant. Deletions in IKZF1 gene were found in 31.3% of BCR-ABL1-like cases. Patients with concurrent IKZF1 and CDKN2A/B, PAX5 or PAR1 region deletions (IKZF1plus profile) had significantly worse progression-free survival than those with sole IKZF1 deletion or IKZF1 wild-type (p=.02). NGS analysis was performed in 54 patients and identified 99 short variants in TP53, JAK2, NRAS, PAX5, CREBBP, NF1, FLT3, ATM, KRAS, RUNX1, and other genes. Seventy-five of these gene variants have not yet been described in B-cell precursor ALL to date. CONCLUSION: This study widens existing knowledge of the BCR-ABL1-like and B-other ALL genomic landscape in the adult population, supports previous findings, and identifies a number of novel gene variants.

• MeSH
• akutní lymfatická leukemie * genetika   MeSH
• dospělí MeSH
• genomika MeSH
• kohortové studie MeSH
• lidé MeSH
• retrospektivní studie MeSH
• stanovení celkové genové exprese MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The purpose of this study was to estimate the additional risk of side effects attributed to internal mammary node irradiation (IMNI) as part of regional lymph node irradiation (RNI) in breast cancer patients and to compare it with estimated overall survival (OS) benefit from IMNI. MATERIAL AND METHODS: Treatment plans (n = 80) with volumetric modulated arc therapy (VMAT) were calculated for 20 patients (4 plans per patient) with left-sided breast cancer from the prospective GATTUM trial in free breathing (FB) and in deep inspiration breath hold (DIBH). We assessed doses to organs at risk ((OARs) lung, contralateral breast and heart) during RNI with and without additional IMNI. Based on the OAR doses, the additional absolute risks of 10-year cardiac mortality, pneumonitis, and secondary lung and breast cancer were estimated using normal tissue complication probability (NTCP) and risk models assuming different age and risk levels. RESULTS: IMNI notably increased the mean OAR doses. The mean heart dose increased upon IMNI by 0.2-3.4 Gy (median: 1.9 Gy) in FB and 0.0-1.5 Gy (median 0.4 Gy) in DIBH. However, the estimated absolute additional 10-year cardiac mortality caused by IMNI was <0.5% for all patients studied except 70-year-old high risk patients (0.2-2.4% in FB and 0.0-1.1% in DIBH). In comparison to this, the published oncological benefit of IMNI ranges between 3.3% and 4.7%. The estimated additional 10-year risk of secondary cancer of the lung or contralateral breast ranged from 0-1.5% and 0-2.8%, respectively, depending on age and risk levels. IMNI increased the pneumonitis risk in all groups (0-2.2%). CONCLUSION: According to our analyses, the published oncological benefit of IMNI outweighs the estimated risk of cardiac mortality even in case of (e.g., cardiac) risk factors during VMAT. The estimated risk of secondary cancer or pneumonitis attributed to IMNI is low. DIBH reduces the estimated additional risk of IMNI even further and should be strongly considered especially in patients with a high baseline risk.

• MeSH
• celková dávka radioterapie * MeSH
• kritické orgány MeSH
• lidé MeSH
• nádory prsu radioterapie   MeSH
• nemoci srdce mortalita   MeSH
• plánování radioterapie pomocí počítače MeSH
• prospektivní studie MeSH
• radiační poranění mortalita   MeSH
• radioterapie škodlivé účinky   mortalita   MeSH
• senioři MeSH
• srdce účinky záření   MeSH
• zadržování dechu MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Introduction: Within an International Atomic Energy Agency (IAEA) co-ordinated research project (CRP), a remote end-to-end dosimetric quality audit for intensity modulated radiation therapy (IMRT)/ volumetric arc therapy (VMAT) was developed to verify the radiotherapy chain including imaging, treatment planning and dose delivery. The methodology as well as the results obtained in a multicentre pilot study and national trial runs conducted in close cooperation with dosimetry audit networks (DANs) of IAEA Member States are presented.Material and methods: A solid polystyrene phantom containing a dosimetry insert with an irregular solid water planning target volume (PTV) and organ at risk (OAR) was designed for this audit. The insert can be preloaded with radiochromic film and four thermoluminescent dosimeters (TLDs). For the audit, radiotherapy centres were asked to scan the phantom, contour the structures, create an IMRT/VMAT treatment plan and irradiate the phantom. The dose prescription was to deliver 4 Gy to the PTV in two fractions and to limit the OAR dose to a maximum of 2.8 Gy. The TLD measured doses and film measured dose distributions were compared with the TPS calculations.Results: Sixteen hospitals from 13 countries and 64 hospitals from 6 countries participated in the multicenter pilot study and in the national runs, respectively. The TLD results for the PTV were all within ±5% acceptance limit for the multicentre pilot study, whereas for national runs, 17 participants failed to meet this criterion. All measured doses in the OAR were below the treatment planning constraint. The film analysis identified seven plans in national runs below the 90% passing rate gamma criteria.Conclusion: The results proved that the methodology of the IMRT/VMAT dosimetric end-to-end audit was feasible for its intended purpose, i.e., the phantom design and materials were suitable; the phantom was easy to use and it was robust enough for shipment. Most importantly the audit methodology was capable of identifying suboptimal IMRT/VMAT delivery.

• MeSH
• celková dávka radioterapie MeSH
• fantomy radiodiagnostické * MeSH
• jaderná energie MeSH
• kritické orgány * MeSH
• lidé MeSH
• mezinárodní agentury MeSH
• pilotní projekty MeSH
• plánování radioterapie pomocí počítače metody   MeSH
• počítačová rentgenová tomografie MeSH
• radiometrie metody   normy   MeSH
• radioterapie s modulovanou intenzitou metody   normy   MeSH
• revize kvality lékařské péče metody   normy   MeSH
• studie proveditelnosti MeSH
• zajištění kvality zdravotní péče MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Background and purpose: A collaborative network between proton therapy (PT) centres in Trento in Italy, Poland, Austria, Czech Republic and Sweden (IPACS) was founded to implement trials and harmonize PT. This is the first report of IPACS with the aim to show the level of harmonization that can be achieved for proton therapy planning of head and neck (sino-nasal) cancer.Methods: CT-data sets of five patients were included. During several face-to-face and online meetings, a common treatment planning protocol was developed. Each centre used its own treatment planning system (TPS) and planning approach with some restrictions specified in the treatment planning protocol. In addition, volumetric modulated arc therapy (VMAT) photon plans were created.Results: For CTV1, the average Dmedian was 59.3 ± 2.4 Gy(RBE) for protons and 58.8 ± 2.0 Gy(RBE) for VMAT (aim was 56 Gy(RBE)). For CTV2, the average Dmedian was 71.2 ± 1.0 Gy(RBE) for protons and 70.6 ± 0.4 Gy(RBE) for VMAT (aim was 70 Gy(RBE)). The average D2% for the spinal cord was 25.1 ± 8.5 Gy(RBE) for protons and 47.6 ± 1.4 Gy(RBE) for VMAT. The average D2% for chiasm was 46.5 ± 4.4 Gy(RBE) for protons and 50.8 ± 1.4 Gy(RBE) for VMAT, respectively. Robust evaluation was performed and showed the least robust plans for plans with a low number of beams.Discussion: In conclusion, several influences on harmonization were identified: adherence/interpretation to/of the protocol, available technology, experience in treatment planning and use of different beam arrangements. In future, all OARs that should be included in the optimization need to be specified in order to further harmonize treatment planning.

• MeSH
• fotony terapeutické užití   MeSH
• kochlea účinky záření   MeSH
• kritické orgány * účinky záření   MeSH
• larynx účinky záření   MeSH
• lidé MeSH
• mezinárodní spolupráce * MeSH
• mozkový kmen účinky záření   MeSH
• nádory hlavy a krku diagnostické zobrazování   radioterapie   MeSH
• nádory nosu diagnostické zobrazování   radioterapie   MeSH
• nádory vedlejších dutin nosních diagnostické zobrazování   radioterapie   MeSH
• nervus opticus účinky záření   MeSH
• parotis účinky záření   MeSH
• plánování radioterapie pomocí počítače metody   MeSH
• počítačová rentgenová tomografie MeSH
• protonová terapie metody   MeSH
• radioterapie s modulovanou intenzitou metody   MeSH
• tumor burden MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Geografické názvy
• Evropa MeSH

UNLABELLED: The International Atomic Energy Agency (IAEA) has a long tradition of supporting development of methodologies for national networks providing quality audits in radiotherapy. A series of co-ordinated research projects (CRPs) has been conducted by the IAEA since 1995 assisting national external audit groups developing national audit programs. The CRP 'Development of Quality Audits for Radiotherapy Dosimetry for Complex Treatment Techniques' was conducted in 2009-2012 as an extension of previously developed audit programs. MATERIAL AND METHODS: The CRP work described in this paper focused on developing and testing two steps of dosimetry audit: verification of heterogeneity corrections, and treatment planning system (TPS) modeling of small MLC fields, which are important for the initial stages of complex radiation treatments, such as IMRT. The project involved development of a new solid slab phantom with heterogeneities containing special measurement inserts for thermoluminescent dosimeters (TLD) and radiochromic films. The phantom and the audit methodology has been developed at the IAEA and tested in multi-center studies involving the CRP participants. RESULTS: The results of multi-center testing of methodology for two steps of dosimetry audit show that the design of audit procedures is adequate and the methodology is feasible for meeting the audit objectives. A total of 97% TLD results in heterogeneity situations obtained in the study were within 3% and all results within 5% agreement with the TPS predicted doses. In contrast, only 64% small beam profiles were within 3 mm agreement between the TPS calculated and film measured doses. Film dosimetry results have highlighted some limitations in TPS modeling of small beam profiles in the direction of MLC leave movements. DISCUSSION: Through multi-center testing, any challenges or difficulties in the proposed audit methodology were identified, and the methodology improved. Using the experience of these studies, the participants could incorporate the auditing procedures in their national programs.

• MeSH
• dozimetry MeSH
• fantomy radiodiagnostické MeSH
• lidé MeSH
• mezinárodní agentury MeSH
• plánování radioterapie pomocí počítače metody   normy   MeSH
• radiometrie přístrojové vybavení   metody   normy   MeSH
• řízení kvality MeSH
• termoluminiscenční dozimetrie přístrojové vybavení   metody   normy   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

BACKGROUND: Adult Langerhans cell histiocytosis is a rare disorder with diverse clinical manifestations and inconsistent treatment outcomes to conventional therapeutic regimens. Cladribine (2-chlorodeoxyadenosine) repeatedly proved effective in cases of relapsed multifocal and multisystem disease forms. In this retrospective study we present an analysis of cladribine in frontline systemic therapy. MATERIAL AND METHODS: A cohort of seven male patients with biopsy proved multisystem (six cases) and multifocal (one case) Langerhans cell histiocytosis received cladribine at a dose of 5 mg/m(2) subcutaneously (five cases) or by two-hour intravenous infusion (two cases) over five consecutive days, every four weeks for a median of four courses (range 4-6). The treatment was enhanced with cyclophosphamide (300 mg intravenously on days 1-5 in cycles 4-6) and corticoids (dexamethasone 24 mg orally or methylprednisolone 250 mg intravenously on days 1-5 in cycles 4-6) in two patients, with radiotherapy (20 Gy on skin or bone lesions) in three patients and with photochemotherapy (psoralen plus ultraviolet A light, PUVA) on skin lesions in one patient. RESULTS: All patients achieved clinically relevant treatment response confirmed by positron emission tomography (PET). Durable complete remissions were maintained in six patients (86%), including two patients with hypophysis involvement, with the median follow-up of 37 months (range 15-94; 49.8 ± 35.2 [ 6 ]). One patient had an aggressive, early relapsing disease requiring further treatment lines. The treatment-related toxicities consisted of transient bone marrow suppression affecting the leukocytes predominantly. Grade 3 lymphopenia occurred in five patients (71%) and grade 3 neutropenia in one patient (14%). CONCLUSION: Cladribine, both as a single agent as well as in combination with an alkylating cytostatic and corticoids, represents an effective treatment option with favorable toxicity profile for adult patients with multisystem or aggressive multifocal form of Langerhans cell histiocytosis.

• MeSH
• antitumorózní látky alkylující terapeutické užití   MeSH
• antitumorózní látky terapeutické užití   MeSH
• cyklofosfamid terapeutické užití   MeSH
• dospělí MeSH
• fotochemoterapie * MeSH
• glukokortikoidy terapeutické užití   MeSH
• histiocytóza z Langerhansových buněk farmakoterapie   radioterapie   MeSH
• kladribin terapeutické užití   MeSH
• kohortové studie MeSH
• kombinovaná farmakoterapie MeSH
• kombinovaná terapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• pozitronová emisní tomografie MeSH
• retrospektivní studie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• antitumorózní látky * terapeutické užití   MeSH
• dospělí MeSH
• histiocytóza z Langerhansových buněk diagnóza   farmakoterapie   MeSH
• indukce remise MeSH
• lidé MeSH
• lokální recidiva nádoru diagnóza   farmakoterapie   MeSH
• thalidomid * analogy a deriváty   terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH

• MeSH
• fatální výsledek MeSH
• karcinom z renálních buněk patofyziologie   sekundární   MeSH
• lidé MeSH
• nádory ledvin patofyziologie   patologie   MeSH
• nádory plic patofyziologie   sekundární   MeSH
• nefrektomie MeSH
• počítačová rentgenová tomografie MeSH
• psoriáza chirurgie   patofyziologie   MeSH
• senioři MeSH
• spontánní regrese nádoru MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH