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Dose-painting after multi-block endoscopic endonasal surgery in sinonasal tumours: protocol for the SinocaRT randomised phase II trial

Por: Thariat · J. · Clarisse · B. · Carsuzaa · F. · Lequesne · J. · Leconte · A. · Larnaudie · A. · Bouter · J. · Liem · X. · Humbert · M. · Patron · V.
Introduction

Sinonasal carcinomas are rare malignancies with an overall poor prognosis. These tumours arise in close proximity to vital structures, critical organs and cranial nerves involved in essential sensory and endocrine functions. Although multimodal treatment strategies combining surgery and radiotherapy (RT) are required to maximise the chances of cure while sparing surrounding tissues and reducing the risk of recurrence, they are associated with substantial cumulative morbidity. Building on high conformality and steep gradients of modern dose-painting RT, multidisciplinarity can be exploited on technical inter-disciplinary aspects. In particular, minimally morbid endoscopic endonasal multi-block surgery (EES), together with accurate histosurgical mapping, can be leveraged to individualise target tumour subvolumes delineation by risk level to avoid unnecessarily large irradiation and reduce the morbidity of RT while maintaining or improving local tumour control.

Methods and analysis

We designed a randomised multicentre phase II study to assess whether EES-based histosurgical mapping delineation and optimisation using a dose-painting approach can reduce treatment-related toxicity compared with standard intensity-modulated RT using conventional delineation in sinonasal carcinomas. The primary endpoint is the proportion of patients free from severe clinically significant radiation-induced toxicity involving the nasal mucosa, eyes, auditory system, endocrine system and/or brain within 3 months following RT completion. Secondary objectives include assessing the proportion of patients free from severe toxicities at 12 months, tumour control, quality of life, tolerance profile, RT plan quality and the association of histoclinical characteristics and radiomic features with toxicities. To ensure tumour control and avoid quality biases on toxicity outcomes, multidisciplinary volume delineation with the surgeon, as well as prospective individual case review (ICR) of the first 2 cases for each centre and both technique arms, and retrospective ICR for all cases, will be conducted.

Eligible patients will be 1:1 randomised between dose-painting based on histosurgical mapping (experimental arm) or standard delineation/optimisation (control arm), with stratification according to RT modality (photons or protons). We plan to enrol 52 patients. RT will start no earlier than 4 weeks and no later than 8 weeks after surgery, and will be delivered over a 7-week period. Patients will be followed-up for 18 months after completion of RT. We hypothesise that dose-painting RT, which relies on extensive interdisciplinary optimisation, will enable a selective de-escalation of irradiated volumes, which should translate into lower treatment-related toxicities.

Ethics and dissemination

Ethical approval was obtained from the Comité de Protection des Personnes Nord-Ouest IV (N°ID-RCB: 2022-A02011-42; cppnordouestiv@univ-lille.fr) on 12 April 2023, and authorisation from the National Agency for Medical and Health Products Safety on 15 May 2023. The most recent amendment (V2) was approved on 25 January 2024. Written informed consent will be obtained from all participants. Final trial results will be published in peer-reviewed journals and adhere to International Committee of Medical Journal Editors guidelines.

Trial registration number

NCT05943119.

Unveiling the burden of long covid in hospital and community settings: findings from the Post-Acute Sequelae of SARS-CoV-2 Network (PASCNET) cohort study in Italys pandemic epicentre

Por: Antolini · L. · Valsecchi · M. G. · Bussi · A. · La Piana · G. · Pagani · E. · Pascarella · M. G. · Patroni · A. · Pellegrino · I. · Pozzi · A. · Sorlini · M. · Ticozzelli · M. · Villa · M. · Zappa · M. · Russo · A. G. · Lucifora · C.
Objectives

Post-COVID-19 condition (PCC) has emerged as a major public health concern. We aimed to estimate the 1-year incidence of PCC in adults with confirmed SARS-CoV-2 infection in Lombardy, Italy, comparing community-managed and hospitalised patients and to assess the prognostic value of the National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) score to support estimation of long-term PCC prevalence.

Design

Retrospective-prospective observational cohort study enrolling patients infected between 1 March 2020 and 31 December 2022. The study visit was conducted between 16 January and 23 December 2024.

Setting

Multicentre study involving seven public hospitals and general practitioners across Lombardy.

Participants

Randomly sampled adults aged 18–70 years with confirmed SARS-CoV-2 infection. Hospitalised patients (HP) were admitted for COVID-19; general practitioner patients (GPP) were managed in the community. The total sample comprised: 1162 (546 HP, 616 GPP).

Intervention

This is an observational study with no active intervention.

Primary and secondary outcome measures

Primary outcome: 1-year incidence of PCC retrospectively assessed at the study visit.

Secondary outcomes: symptom profiles, long-term PCC prevalence at the study visit and predictive value of the NIH RECOVER score.

Results

Median age was 57.1 years in HP and 42.9 years in GPP; 66.1% of HP and 47.7% of GPP were male. PCC developed in 280 patients (223 HP, 57 GPP). The 1-year cumulative incidence was 39.9% in HP (95% CI 35.9% to 44.1%) and 9.1% in GPP (95% CI 7.1% to 11.7%). The NIH RECOVER score was associated with PCC at 1 year (OR 1.18, 95% CI 1.14 to 1.21). Model-based long-term PCC prevalence was 31.8% in HP and 6.3% in GPP.

Conclusions

PCC remained frequent and heterogeneous, particularly among previously HP. In this cohort, the NIH RECOVER score showed prognostic value for estimating longer-term PCC burden. These findings underscore the need for structured long-term follow-up across both hospital and primary care settings.

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