Hydrogen bonding patterns and C-H...π interactions in the structure of the antiparkinsonian drug (R)-rasagiline mesylate determined using laboratory and synchrotron X-ray powder diffraction data.

The structure of (R)-rasagiline mesylate [(R)-RasH+·Mes-], an active pharmaceutical ingredient used to treat Parkinson's disease, is presented. The structure was determined from laboratory and synchrotron powder diffraction data, refined using the Rietveld method, and validated and optimized using dispersion-corrected DFT calculations. The unit-cell parameters obtained in both experiments are in good agreement and the refinement with both datasets converged to good agreement factors. The final parameters obtained from laboratory data were a = 5.4905 (8), b = 6.536 (2), c = 38.953 (3) Å, V = 1398.0 (4) Å3 and from synchrotron powder data were a = 5.487530 (10) Å, b = 6.528939 (12) Å, c = 38.94313 (9) Å, V = 1395.245 (5) Å3 with Z = 4 and space group P212121. Preferred orientation was properly accounted for using the synchrotron radiation data, leading to a March-Dollase parameter of 1.140 (1) instead of the 0.642 (1) value obtained from laboratory data. In the structure, (R)-RasH+ moieties form layers parallel to the ab plane connected by mesylate ions through N-H...O and C-H...O hydrogen bonds. These layers stack along the c axis and are further connected by C-H...π interactions. Hirshfeld surface analysis and fingerprint plot calculations indicate that the main interactions are: H...H (50.9%), H...C/C...H (27.1%) and H...O/O...H (21.1%).

Hospital-based proton therapy implementation during the COVID pandemic: early clinical and research experience in a European academic institution.

INTRODUCTION: A rapid deploy of unexpected early impact of the COVID pandemic in Spain was described in 2020. Oncology practice was revised to facilitate decision-making regarding multimodal therapy for prevalent cancer types amenable to multidisciplinary treatment in which the radiotherapy component searched more efficient options in the setting of the COVID-19 pandemic, minimizing the risks to patients whilst aiming to guarantee cancer outcomes. METHODS: A novel Proton Beam Therapy (PBT), Unit activity was analyzed in the period of March 2020 to March 2021. Institutional urgent, strict and mandatory clinical care standards for early diagnosis and treatment of COVID-19 infection were stablished in the hospital following national health-authorities' recommendations. The temporary trends of patients care and research projects proposals were registered. RESULTS: 3 out of 14 members of the professional staff involved in the PBR intra-hospital process had a positive test for COVID infection. Also, 4 out of 100 patients had positive tests before initiating PBT, and 7 out of 100 developed positive tests along the weekly mandatory special checkup performed during PBT to all patients. An update of clinical performance at the PBT Unit at CUN Madrid in the initial 500 patients treated with PBT in the period from March 2020 to November 2022 registers a distribution of 131 (26%) pediatric patients, 63 (12%) head and neck cancer and central nervous system neoplasms and 123 (24%) re-irradiation indications. In November 2022, the activity reached a plateau in terms of patients under treatment and the impact of COVID pandemic became sporadic and controlled by minor medical actions. At present, the clinical data are consistent with an academic practice prospectively (NCT05151952). Research projects and scientific production was adapted to the pandemic evolution and its influence upon professional time availability. Seven research projects based in public funding were activated in this period and preliminary data on molecular imaging guided proton therapy in brain tumors and post-irradiation patterns of blood biomarkers are reported. CONCLUSIONS: Hospital-based PBT in European academic institutions was impacted by COVID-19 pandemic, although clinical and research activities were developed and sustained. In the post-pandemic era, the benefits of online learning will shape the future of proton therapy education.

Practice-oriented solutions integrating intraoperative electron irradiation and personalized proton therapy for recurrent or unresectable cancers: Proof of concept and potential for dual FLASH effect.

Background: Oligo-recurrent disease has a consolidated evidence of long-term surviving patients due to the use of intense local cancer therapy. The latter combines real-time surgical exploration/resection with high-energy electron beam single dose of irradiation. This results in a very precise radiation dose deposit, which is an essential element of contemporary multidisciplinary individualized oncology. Methods: Patient candidates to proton therapy were evaluated in Multidisciplinary Tumor Board to consider improved treatment options based on the institutional resources and expertise. Proton therapy was delivered by a synchrotron-based pencil beam scanning technology with energy levels from 70.2 to 228.7 MeV, whereas intraoperative electrons were generated in a miniaturized linear accelerator with dose rates ranging from 22 to 36 Gy/min (at Dmax) and energies from 6 to 12 MeV. Results: In a period of 24 months, 327 patients were treated with proton therapy: 218 were adults, 97 had recurrent cancer, and 54 required re-irradiation. The specific radiation modalities selected in five cases included an integral strategy to optimize the local disease management by the combination of surgery, intraoperative electron boost, and external pencil beam proton therapy as components of the radiotherapy management. Recurrent cancer was present in four cases (cervix, sarcoma, melanoma, and rectum), and one patient had a primary unresectable locally advanced pancreatic adenocarcinoma. In re-irradiated patients (cervix and rectum), a tentative radical total dose was achieved by integrating beams of electrons (ranging from 10- to 20-Gy single dose) and protons (30 to 54-Gy Relative Biological Effectiveness (RBE), in 10-25 fractions). Conclusions: Individual case solution strategies combining intraoperative electron radiation therapy and proton therapy for patients with oligo-recurrent or unresectable localized cancer are feasible. The potential of this combination can be clinically explored with electron and proton FLASH beams.

Intra-Operative Electron Radiation Therapy: An Update of the Evidence Collected in 40 Years to Search for Models for Electron-FLASH Studies.

INTRODUCTION: The clinical practice and outcome results of intraoperative electron radiation therapy (IOeRT) in cancer patients have been extensively reported over 4 decades. Electron beams can be delivered in the promising FLASH dose rate. METHODS AND MATERIALS: Several cancer models were approached by two alternative radiobiological strategies to optimize local cancer control: boost versus exclusive IOeRT. Clinical outcomes are revisited via a bibliometric search performed for the elaboration of ESTRO/ACROP IORT guidelines. RESULTS: In the period 1982 to 2020, a total of 19,148 patients were registered in 116 publications concerning soft tissue sarcomas (9% of patients), unresected and borderline-resected pancreatic cancer (22%), locally recurrent and locally advanced rectal cancer (22%), and breast cancer (45%). Clinical outcomes following IOeRT doses in the range of 10 to 25 Gy (with or without external beam fractionated radiation therapy) show a wide range of local control from 40 to 100% depending upon cancer site, histology, stage, and treatment intensity. Constraints for normal tissue tolerance are important to maintain tumor control combined with acceptable levels of side effects. CONCLUSIONS: IOeRT represents an evidence-based approach for several tumor types. A specific risk analysis for local recurrences supports the identification of cancer models that are candidates for FLASH studies.

Crystal structure from X-ray powder diffraction data, DFT-D calculation, Hirshfeld surface analysis, and energy frameworks of (RS)-trichlorme-thia-zide.

The structure of racemic (RS)-trichlorme-thia-zide [systematic name: (RS)-6-chloro-3-(di-chloro-meth-yl)-1,1-dioxo-3,4-di-hydro-2H-1λ6,2,4-benzo-thia-di-azine-7-sulfonamide], C8H8Cl3N3O4S2 (RS-TCMZ), a diuretic drug used in the treatment of oedema and hypertension, was determined from laboratory X-ray powder diffraction data using DASH [David et al. (2006 ▸). J. Appl. Cryst. 39, 910-915.], refined by the Rietveld method with TOPAS-Academic [Coelho (2018 ▸). J. Appl. Cryst. 51, 210-218], and optimized using DFT-D calculations. The extended structure consists of head-to-tail dimers connected by π-π inter-actions which, in turn, are connected by C-Cl⋯π inter-actions. They form chains propagating along [101], further connected by N-H⋯O hydrogen bonds to produce layers parallel to the ac plane that stack along the b-axis direction, connected by additional N-H⋯O hydrogen bonds. The Hirshfeld surface analysis indicates a major contribution of H⋯O and H⋯Cl inter-actions (32.2 and 21.7%, respectively). Energy framework calculations confirm the major contribution of electrostatic inter-actions (E elec) to the total energy (E tot). A comparison with the structure of S-TCMZ is also presented.

Corrigendum: Practice-oriented solutions integrating intraoperative electron irradiation and personalized proton therapy for recurrent or unresectable cancers: Proof of concept and potential for dual FLASH effect.

[This corrects the article DOI: 10.3389/fonc.2022.1037262.].

Synthesis, crystal structure, Hirshfeld surface analysis and energy framework calculations of trans-3,7,9,9-tetra-methyl-10-(prop-2-yn-1-yl)-1,2,3,4,4a,9,9a,10-octa-hydro-acridine.

The title heterocyclic compound, C20H27N, has been prepared in good yield (72%) via a BiCl3-catalyzed cationic Povarov reaction between N-propargyl-4-methyl-aniline and (±)-citronellal. The X-ray single-crystal study indicates that the structure consists of mol-ecules connected by C-H⋯π contacts to produce chains, which pack in a sandwich-herringbone fashion along the b-axis direction. Hirshfeld surface analysis indicates that H⋯H inter-actions dominate by contributing 79.1% to the total surface. Energy frameworks and DFT calculations indicate a major contribution of dispersive forces to the total inter-action energy.

Intra-operative electron beam radiotherapy for newly diagnosed and recurrent malignant gliomas: feasibility and long-term outcomes.

INTRODUCTION: Intra-operative electron beam radiotherapy (IOERT) is an alternative to dose escalation for the treatment of central nervous system tumors. The objective of this study was to describe the feasibility and long-term outcomes of IOERT in the treatment of primary and recurrent gliomas. MATERIALS AND METHODS: From January 1992 through December 2002, all patients treated with IOERT at the Hospital San Francisco de Asis, Madrid/Spain were retrospectively reviewed. The selection criteria included patients with superficial tumors, KPS >70 % and lesions <6 cm. Irradiation was administered in one section. The prescribed dose considered the amount of post-resection residual tumor, previous radiotherapy and the tolerance level of brain structures exposed to IOERT. RESULTS: There were 17 patients (53 %) with newly diagnosed malignant brain gliomas and 15 patients with recurrent tumors. The delivered dose varied from 8 to 20 Gy (median 12.5 Gy) for primary and from 8 to 16 Gy (median 10 Gy) for recurrent tumors. The median overall survival for the entire cohort was 13 months (14 and 10.4 months for the primary and recurrent, respectively). Three patients presented with radionecrosis, one patient with osteomyelitis at the craniotomy bone flap, one with intracerebral hemorrhage, and another patient experienced a pulmonary embolism. CONCLUSIONS: IOERT is a feasible technique and can be viewed as a tool in the treatment of newly diagnosed or recurrent brain gliomas.