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Papers by sofia rivera

European Journal of Cancer

Introduction: Oncology treatments are constantly and rapidly evolving. We aimed at highlighting t... more Introduction: Oncology treatments are constantly and rapidly evolving. We aimed at highlighting the latest radiation therapy practice changing trials and emerging concepts, through an overview of recent randomised clinical trials (RCTs). Materials and methods: Requests were performed in the Medline database to identify all publications reporting radiation therapy RCTs from 2018 to 2021. Results: Recent RCTs sustained the role of newer combinatorial strategies through radioimmunotherapy for early stage or metastatic lung cancer, newer pro-apoptotic agents (e.g. debio 1143 in locoregionally advanced head and neck squamous cell carcinoma) or nanoparticles (e.g. NBTXR3 in locally advanced soft-tissue sarcoma). High-tech radiotherapy allows intensifying treatments and gaining ground in some indications through the development of stereotactic body radiotherapy for example. First randomised evidence on personalised radiation therapy through imaging-based (18 FDG positron emission tomography-computed tomography for lung cancer or early stage unfavourable Hodgkin lymphoma, PMSA positron emission tomography-computed tomography or magnetic resonance imaging for high-risk prostate cancer) or biological biomarkers (PSA for prostate cancer, HPV for head and neck cancer, etc)

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Background: Moderately hypofractionated whole-breast radiotherapy (HFRT) has proven to be as safe... more Background: Moderately hypofractionated whole-breast radiotherapy (HFRT) has proven to be as safe and efficient as normofractionated radiotherapy (NFRT) in randomized trials resulting in major changes in clinical practice. Toxicity rates observed in selected clinical trial patients may differ from those observed in unselected patients with possible comorbidities and frailty in real-life. This study aimed to examine the influence of HFRT versus NFRT on acute toxicity and identify risks factors of dermatitis in real-life patients.Materials and Methods: Prospective data from breast cancer patients, treated with locoregional radiotherapy between November 2015 and February 2020 in 3 comprehensive cancer centers, were collected. Through a systematic data-farming strategy, acute toxicity evaluation forms (CTCAEv4.0) were prospectively completed and extracted electronically. The results from each center were then anonymously merged into a single database for analysis. A Chi-2 test was used ...

Cancer Research, 2022

Purpose: In this paper, we describe the methodology used, and provide a first characterization of... more Purpose: In this paper, we describe the methodology used, and provide a first characterization of the study population and radiotherapy (RT) data in CANTO-RT (CANcer TOxicities Radiotherapy), the largest available multicenter prospective cohort of early breast cancer (BC) patients treated with RT that aims to identify predictors of development, and persistence of long-term toxicities. Methods: CANTO (NCT01993498) is a French prospective clinical cohort study of 10 150 patients with stage I-III BC from 26 cancer centers. Patients matching all CANTO inclusion and exclusion criteria, who received RT and were still in follow up, in the 10 top recruiting CANTO centers, with a minimum follow up of 3 years, were selected for CANTO-RT. Eligible patients had breast/chest wall +/- lymph node RT with curative intent. Individual full DICOM RT files (CT, RT Structure, RT Dose, RT Plan) were collected, anonymized, structured and analyzed on the CANTO-RT/UNITRAD web platform using AQUILAB Share Pl...

Cancer Research, 2022

Background Fatigue is a common and disabling symptom experienced by patients (pts) after breast c... more Background Fatigue is a common and disabling symptom experienced by patients (pts) after breast cancer (BC) treatment, significantly impacting their quality of life. However, this complex and multidimensional symptom often remains poorly managed. Previous studies identified some treatment-related factors associated with increased risk of developing severe and persistent fatigue. A better understanding of the relationship between treatment modalities and fatigue may help prevention and management strategies.Multimodal BC treatment often includes radiotherapy (RT) to the breast and/or nodal areas. RT modalities are now increasingly personalized. While an association between receipt of RT and fatigue after BC was previously suggested, large-scale data analyzing the impact of distinct RT modalities on fatigue are lacking.Our aim was to assess the impact of RT modalities on fatigue one year after treatment among patients with early-stage BC. Methods CANcer TOxicity (CANTO; NCT01993498) i...

Cancer Research, 2022

Background and Objectives: Despite the proven benefits on reducing time to recurrence and improvi... more Background and Objectives: Despite the proven benefits on reducing time to recurrence and improving survival, recent studies indicate that only half or less of patients with early stage breast cancer (BC) complete their recommended full-course of adjuvant ET. Findings suggested that adherence therefore remains a challenge for both patients and professionals, with differences in representations that remain poorly understood. The main objective of this study is to investigate BC patient’s perceptions about ET. Secondary objectives are: (1): to capture potential gaps between their perceptions and the representations of their HCP (2): to explore preferences in patients regarding programs aimed to improve adherence to ET. Methods We conducted separately focus groups with patients and HCP to capture a multilevel framework regarding non-adherence. Inclusion criteria for patients’ focus groups were: non metastatic hormone-receptor positive (HR+) BC; ≥18 years old; premenopausal at time of d...

Table S3. Genes differentially expressed between relapsed tumors and non-relapsed tumors. (DOCX 2... more Table S3. Genes differentially expressed between relapsed tumors and non-relapsed tumors. (DOCX 23 kb)

Figure S1. Graphic table of contents. (PDF 561 kb)

Table S1. Breast Curie gene panel for targeted NGS. (DOCX 21 kb)

International Journal of Radiation Oncology*Biology*Physics, 2020

Cancer/Radiothérapie, 2020

Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on ... more Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

Radiotherapy and Oncology, 2021

Radiotherapy and Oncology, 2021

Purpose or Objective To limit hospital visits and transportation of the patients with early breas... more Purpose or Objective To limit hospital visits and transportation of the patients with early breast cancer (BC) especially during the covid-19 pandemic, we aimed to implement a workflow of treatment to prepare and deliver adjuvant breast radiotherapy (RT) within 1 week. Materials and Methods Based on the Fast Forward RT schedule of 5 fractions of 5.2 Gy over 5 days for adjuvant BC, we designed a workflow to perform BC RT over 1 week from the first RT consultation to the end of treatment (figure 1). Patients were seen in consultation on Monday morning. The planning CT was carried out immediately after the consultation. A deep inspiration breath-hold technique was systematically offered to all patients. Automatic delineation using an artificial Intelligence (AI) based model with ART-PlanTM software was first corrected by a junior radiation oncologist (RO) then, independently by a senior RO. As 3D conformal RT failed to achieve dose constraints of the fast forward trial in many cases (due to breast hotspots), we developed a restricted IMRT (rIMRT) technique based on 2 tangential beams (internal and external) using inverse planning restricted optimization parameters to improve the dose homogeneity. Treatment planning was semi-automated by scripting the creation and optimization steps of rIMRT plans. After validation of the reliability of rIMRT treatment delivery by patient-specific quality assurance (PSQA) with gamma index evaluation on 20 patients, we decided to abandon systematic PSQAs. In-vivo dosimetry was validated by end-to-end controls and performed for each patient during the first fraction on Monday afternoon. Daily repositioning was controlled by portal images of the largest segment of each beam. Structured baseline, end of treatment and follow up evaluation forms were used to prospectively collect toxicities and oncological outcomes at each consultation. Patient agreement for data collection and analysis was prospectively obtained. $Φg Results From February 2021 to March 2021, the 1-week breast procedure was proposed to up to 3 patients/week, >65 years, in complete resection after conservative surgery, with pT1-T3 N0 BC, without tumor bed boost or regional lymph nodes irradiation. Six out of seven patients (85.7%) accepted the 1-week breast procedure. All procedures were successfully conducted over 5 days with complete patient and RT team satisfaction. A followup of acute toxicities by online consultation on day 10, structured evaluation forms and management decision trees has been implemented for these patients. No grade >2 acute toxicities (CTACE V4.0) have been reported so far. Conclusion The successful implementation of this comprehensive 1-week breast workflow with AI based delineation and semi-automated rIMRT without PSQA demonstrates the practical feasibility of the whole procedure over 5 days reducing drastically the coming-and-going to the hospital and the overall RT management time per patient. Our work opens the way for further development of comprehensive compact workflows in various settings.

Radiotherapy and Oncology, 2021

PURPOSE To describe the quality assurance (QA) program and early toxicities in the phase III rand... more PURPOSE To describe the quality assurance (QA) program and early toxicities in the phase III randomized trial BONBIS (NCT00907868) on the role of a localized radiation boost in ductal carcinoma in situ (DCIS). MATERIALS AND METHODS From November 2008 to July 2014, 2004 patients were randomized in arm A (only whole breast radiotherapy, WBRT) and arm B (WBRT+boost). The QA program involved 44 participant centers that performed the dummy run (DR). Compliance and uniformity of clinical target volume (CTV) delineations, and dose prescription and delivery according to the BONBIS trial radiotherapy guidelines were analyzed. Acute toxicities (during and up to 3 months after radiotherapy completion, NCI-CTCAE v3.0 classification) were evaluated in 1929 patients. RESULTS The differences in whole breast CTV (CTV1) and planning target volume (PTV1) were ≤10%, and the differences in boost CTV (CTV2) and PTV (PTV2) were ≥20% compared with the reference DR values; 95% of the prescribed dose encompassed 98.7% and 100% of the median CTV1 and CTV2. Grade ≥2 breast erythema (38.3% vs. 22.4% of grade 2 and 5.4% vs. 2.1% of grade 3, p<0.001), grade ≥2 dermatitis (2.8% vs. 0.7%, p<0.001), and grade 2 hyperpigmentation (6.9% vs. 3.6%, p=0.005) were more frequent in arm B than arm A. No acute lung or cardiac toxicity was observed. Smoking history, large breast size, and large breast CTV were strong predictive factors of grade ≥2 acute skin toxicities. CONCLUSIONS The QA program showed deviations in breast and tumor bed delineation. The boost significantly increased acute skin toxicities.

Cancer/Radiothérapie, 2021

Introduction et but de l’etude Le cancer du sein inflammatoire est une entite de mauvais pronosti... more Introduction et but de l’etude Le cancer du sein inflammatoire est une entite de mauvais pronostic, representant entre 1 et 5 % des nouveaux cas de cancer du sein et correspond au stade T4d dans la derniere classification TNM. Pour les formes localisees, le traitement le plus frequemment propose est un traitement multimodal associant la chimiotherapie, la chirurgie et la radiotherapie. L’objectif de cette etude retrospective multicentrique etait d’evaluer la survie sans progression et la survie globale chez des patientes, issues de huit centres francais, atteintes d’un cancer du sein inflammatoire localise et de determiner differents facteurs pronostiques. Materiel et methodes Cette etude incluait les patientes prises en charge pour un cancer du sein inflammatoire localise (T4d, Nx, M0) entre 2010 et 2017. Les patientes ayant moins de 6 mois de suivi ont ete exclues de l’etude, sauf en cas de deces. Les taux de survie globale et de survie sans progression a 2 et 5 ans ainsi que le caractere pronostique des differents scores histologiques (Sataloff et Chevalier) ont ete determines. Resultats et analyse statistique Nous avons inclus 369 patientes atteintes d’un cancer du sein inflammatoire localise avec un âge median de 54 ± 15 ans, dont 46 (12 %) avaient plus de 70 ans. Au moment du diagnostic les patientes avaient une atteinte ganglionnaire dans 83 % des cas (57 % N1, 11 % de N2, 15 % de N3). La grande majorite des patientes ont eu une chimiotherapie premiere neoadjuvante (n = 352, 95 %), suivie d’une chirurgie (n = 325, 88 %), suivie d’une radiotherapie postoperatoire (n = 296, 80 %). Une chimiotherapie premiere neoadjuvante etait donnee chez 98 % des patientes de moins de 70 ans (n = 310) et chez 87 % des plus de 70 ans (n = 40) (p = 0,002). Seulement 32 patientes (9 %) avaient ete irradiees en situation preoperatoire, soit de maniere exclusive (n = 14, 4 %), soit de maniere concomitante a une chimiotherapie (n = 18, 5 %). Chez les patientes qui avaient recu une chimiotherapie neoadjuvante, 117 (soit 37 %) avaient eu un effet therapeutique total ou presque au niveau de la tumeur mammaire parmi les 317 patientes evaluables (TA selon Sataloff). Apres un suivi median de 50 mois (extremes : 28–74 mois), les taux de survie globale a 2 ans et 5 ans etait respectivement de 88 % (intervalle de confiance a 95 % [IC95 %] : 84–91 %] et 73 % (IC95 % : 67–78 %), tandis que les taux de survie sans progression a 2 ans et 5 ans etaient respectivement de 72 % (IC95 % : 67–76 %) et 54 % (IC95 % : 48–59 %). Un score de Sataloff TB, TC ou TD etait un facteur de risque de deces (hazard ratio [HR] : 2,1 [1,2 ;3,6], p = 0,006), de meme qu’un score de Chevalier de 2, 3 ou 4 (HR : 3,2 [1,4 ;7,3], p = 0,006). Conclusion A notre connaissance, notre etude est actuellement la plus grande serie multicentrique de patientes atteintes d’un cancer du sein inflammatoire localise. L’inclusion des patientes traitees entre 2010 et 2017 permet de refleter les pratiques therapeutiques actuelles. Malgre cela, le cancer du sein inflammatoire localise apparait encore comme une maladie de mauvais pronostic. Une mauvaise reponse histologique a la chimiotherapie neoadjuvante est dans notre etude un facteur pronostique pejoratif et invite a s’interroger sur d’eventuelles strategies d’intensification chez ces patientes.

Cancer/Radiothérapie, 2020

Cancer/Radiothérapie, 2020

Introduction et but de l’etude Plusieurs etudes de phase III randomisees ont montre la non-inferi... more Introduction et but de l’etude Plusieurs etudes de phase III randomisees ont montre la non-inferiorite de la radiotherapie hypofractionnee moderee par comparaison a l’irradiation normofractionnee en termes de survie globale, rechute locale et survenue de toxicite aigue et tardive dans le traitement adjuvant des tumeurs du sein. La radiotherapie hypofractionnee moderee est donc devenue le standard pour l’irradiation mammaire. Les donnees de vie reelle, prospectives, multicentriques et structurees pourraient contribuer a la validation des conclusions de ces essais. L’objectif de notre etude etait de comparer la toxicite aigue mammaire en vie reelle apres irradiation hypofractionnee moderee ou normofractionnee entre differents centres. Materiel et methodes Une fiche standardisee d’evaluation (FSE) prospective de la toxicite aigue a ete mise en place progressivement dans Mosaiq©. De novembre 2015 a fevrier 2020, trois centres (Gustave-Roussy, Jean-Godinot, Paul-Straus ont systematiquement complete cette fiche en fin de traitement permettant une gradation de la toxicite aigue observees selon les Common Terminology Criteria for Adverse Events (CTCAE V4). Une extraction automatique des donnees (patient, tumeur, traitement et toxicite aigue) a ensuite ete realisee. Resultats et analyse statistique Parmi 3518 patients, les dossiers de 2052 patients traites avec un complement d’irradiation du lit tumoral ont ete analyses (1343 du centre Paul-Straus [soit 65,4 %], 521 de Jean-Godinot [soit 25,4 %] et 188 de Gustave-Roussy [soit 9,2 %]) dont 645 traites par irradiation hypofractionnee moderee (majoritairement 2,67 Gy par fraction, soit 31,4 %) et 1407 par irradiation normofractionnee (soit 68,6 %). L’âge median etait de 60 ans (extremes : 24-93 ans) avec pour 97,7 % un indice de performance selon l’Organisation mondiale de la sante (OMS) de 0-1, pour 72,0 % une tumeur exprimant des recepteurs estrogeniques, 62,7 % des recepteurs a la progesterone et 9,9 % HER + + + ; majoritairement de stade T1-T2 (85,5 %), N0 (69,3 %), M0 (84,0 %). Dans chaque centre, la toxicite aigue de la radiotherapie hypofractionnee moderee n’etait pas superieure a celle de la radiotherapie normofractionnee. Apres radiotherapie hypofractionnee moderee, une difference statistiquement significative a ete observee entre les centres en termes de dermite radique de grade 2-3 (contre 0-1 ; Chi2 = 25,3 ; p Tableau 1 ). Conclusion Notre etude a mis en evidence des differences de toxicite aigue entre centres apres une irradiation mammaire avec un complement d’irradiation. Cette heterogeneite pourrait s’expliquer par des differences de population, des fluctuations d’echantillonnage, une subjectivite dans la gradation ou etre liee au traitement. La saisie prospective se poursuit, s’integrant a la pratique clinique. De nouveaux centres utilisent la fiche standardisee d’evaluation, ce qui permettra des analyses conjointes ulterieures et un suivi de la toxicite aigue.

Frontiers in Oncology, 2020

European Journal of Cancer, 2020

fraction neoadjuvant radiotherapy is under study. We sought to investigate the rate of pathologic... more fraction neoadjuvant radiotherapy is under study. We sought to investigate the rate of pathologic response and postoperative toxicities related to delaying surgery after neoadjuvant radiotherapy. Methods: Women 65 years of age or older with a new diagnosis of stage I unifocal luminal A breast cancer were eligible for inclusion. A single 20 Gy dose of radiotherapy to the primary breast tumor was given, followed by breast-conserving surgery 3 months later. The primary endpoint was the pathologic response rate assessed by microscopic evaluation using the Miller-Payne system. The secondary endpoint was the incidence of radiation toxicity, graded according to the Common Terminology Criteria for Adverse Events (CTCAE). The toxicity was planned to be assessed at 6 weeks, 4 months, 12 months and yearly for up to 5 years after radiotherapy. Results: To date, 13 patients have been successfully treated and had completed the 4-month follow-up. Median age of patients was 71 years (range: 65-83 years). Neoadjuvant radiotherapy resulted in a tumour pathologic response in 11 of 13 patients with a median residual cellularity of 1% (range: 0-10%). At the 4 months' toxicity assessment, 10 patients developed grade 1 toxicities (dermatitis, telangiectasia, fibrosis, breast pain, breast swelling and chronic mastitis), and 3 patients developed grade 2 toxicities (dermatitis, fibrosis and skin or wound infection). No grade 3 or higher toxicities were noted. Conclusion: This study demonstrates that delaying surgery after a single fraction of neoadjuvant radiotherapy can lead to a high level of pathologic response in most patients and is relatively well tolerated with acceptable toxicity. Continued follow up of our patients and subsequent larger trials are needed to better assess the late radiation toxicities as well as the optimal fractionation and timing of this novel technique in the management of earlystage breast cancer.

European Journal of Cancer

Introduction: Oncology treatments are constantly and rapidly evolving. We aimed at highlighting t... more Introduction: Oncology treatments are constantly and rapidly evolving. We aimed at highlighting the latest radiation therapy practice changing trials and emerging concepts, through an overview of recent randomised clinical trials (RCTs). Materials and methods: Requests were performed in the Medline database to identify all publications reporting radiation therapy RCTs from 2018 to 2021. Results: Recent RCTs sustained the role of newer combinatorial strategies through radioimmunotherapy for early stage or metastatic lung cancer, newer pro-apoptotic agents (e.g. debio 1143 in locoregionally advanced head and neck squamous cell carcinoma) or nanoparticles (e.g. NBTXR3 in locally advanced soft-tissue sarcoma). High-tech radiotherapy allows intensifying treatments and gaining ground in some indications through the development of stereotactic body radiotherapy for example. First randomised evidence on personalised radiation therapy through imaging-based (18 FDG positron emission tomography-computed tomography for lung cancer or early stage unfavourable Hodgkin lymphoma, PMSA positron emission tomography-computed tomography or magnetic resonance imaging for high-risk prostate cancer) or biological biomarkers (PSA for prostate cancer, HPV for head and neck cancer, etc)

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Background: Moderately hypofractionated whole-breast radiotherapy (HFRT) has proven to be as safe... more Background: Moderately hypofractionated whole-breast radiotherapy (HFRT) has proven to be as safe and efficient as normofractionated radiotherapy (NFRT) in randomized trials resulting in major changes in clinical practice. Toxicity rates observed in selected clinical trial patients may differ from those observed in unselected patients with possible comorbidities and frailty in real-life. This study aimed to examine the influence of HFRT versus NFRT on acute toxicity and identify risks factors of dermatitis in real-life patients.Materials and Methods: Prospective data from breast cancer patients, treated with locoregional radiotherapy between November 2015 and February 2020 in 3 comprehensive cancer centers, were collected. Through a systematic data-farming strategy, acute toxicity evaluation forms (CTCAEv4.0) were prospectively completed and extracted electronically. The results from each center were then anonymously merged into a single database for analysis. A Chi-2 test was used ...

Cancer Research, 2022

Purpose: In this paper, we describe the methodology used, and provide a first characterization of... more Purpose: In this paper, we describe the methodology used, and provide a first characterization of the study population and radiotherapy (RT) data in CANTO-RT (CANcer TOxicities Radiotherapy), the largest available multicenter prospective cohort of early breast cancer (BC) patients treated with RT that aims to identify predictors of development, and persistence of long-term toxicities. Methods: CANTO (NCT01993498) is a French prospective clinical cohort study of 10 150 patients with stage I-III BC from 26 cancer centers. Patients matching all CANTO inclusion and exclusion criteria, who received RT and were still in follow up, in the 10 top recruiting CANTO centers, with a minimum follow up of 3 years, were selected for CANTO-RT. Eligible patients had breast/chest wall +/- lymph node RT with curative intent. Individual full DICOM RT files (CT, RT Structure, RT Dose, RT Plan) were collected, anonymized, structured and analyzed on the CANTO-RT/UNITRAD web platform using AQUILAB Share Pl...

Cancer Research, 2022

Background Fatigue is a common and disabling symptom experienced by patients (pts) after breast c... more Background Fatigue is a common and disabling symptom experienced by patients (pts) after breast cancer (BC) treatment, significantly impacting their quality of life. However, this complex and multidimensional symptom often remains poorly managed. Previous studies identified some treatment-related factors associated with increased risk of developing severe and persistent fatigue. A better understanding of the relationship between treatment modalities and fatigue may help prevention and management strategies.Multimodal BC treatment often includes radiotherapy (RT) to the breast and/or nodal areas. RT modalities are now increasingly personalized. While an association between receipt of RT and fatigue after BC was previously suggested, large-scale data analyzing the impact of distinct RT modalities on fatigue are lacking.Our aim was to assess the impact of RT modalities on fatigue one year after treatment among patients with early-stage BC. Methods CANcer TOxicity (CANTO; NCT01993498) i...

Cancer Research, 2022

Background and Objectives: Despite the proven benefits on reducing time to recurrence and improvi... more Background and Objectives: Despite the proven benefits on reducing time to recurrence and improving survival, recent studies indicate that only half or less of patients with early stage breast cancer (BC) complete their recommended full-course of adjuvant ET. Findings suggested that adherence therefore remains a challenge for both patients and professionals, with differences in representations that remain poorly understood. The main objective of this study is to investigate BC patient’s perceptions about ET. Secondary objectives are: (1): to capture potential gaps between their perceptions and the representations of their HCP (2): to explore preferences in patients regarding programs aimed to improve adherence to ET. Methods We conducted separately focus groups with patients and HCP to capture a multilevel framework regarding non-adherence. Inclusion criteria for patients’ focus groups were: non metastatic hormone-receptor positive (HR+) BC; ≥18 years old; premenopausal at time of d...

Table S3. Genes differentially expressed between relapsed tumors and non-relapsed tumors. (DOCX 2... more Table S3. Genes differentially expressed between relapsed tumors and non-relapsed tumors. (DOCX 23 kb)

Figure S1. Graphic table of contents. (PDF 561 kb)

Table S1. Breast Curie gene panel for targeted NGS. (DOCX 21 kb)

International Journal of Radiation Oncology*Biology*Physics, 2020

Cancer/Radiothérapie, 2020

Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on ... more Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

Radiotherapy and Oncology, 2021

Radiotherapy and Oncology, 2021

Purpose or Objective To limit hospital visits and transportation of the patients with early breas... more Purpose or Objective To limit hospital visits and transportation of the patients with early breast cancer (BC) especially during the covid-19 pandemic, we aimed to implement a workflow of treatment to prepare and deliver adjuvant breast radiotherapy (RT) within 1 week. Materials and Methods Based on the Fast Forward RT schedule of 5 fractions of 5.2 Gy over 5 days for adjuvant BC, we designed a workflow to perform BC RT over 1 week from the first RT consultation to the end of treatment (figure 1). Patients were seen in consultation on Monday morning. The planning CT was carried out immediately after the consultation. A deep inspiration breath-hold technique was systematically offered to all patients. Automatic delineation using an artificial Intelligence (AI) based model with ART-PlanTM software was first corrected by a junior radiation oncologist (RO) then, independently by a senior RO. As 3D conformal RT failed to achieve dose constraints of the fast forward trial in many cases (due to breast hotspots), we developed a restricted IMRT (rIMRT) technique based on 2 tangential beams (internal and external) using inverse planning restricted optimization parameters to improve the dose homogeneity. Treatment planning was semi-automated by scripting the creation and optimization steps of rIMRT plans. After validation of the reliability of rIMRT treatment delivery by patient-specific quality assurance (PSQA) with gamma index evaluation on 20 patients, we decided to abandon systematic PSQAs. In-vivo dosimetry was validated by end-to-end controls and performed for each patient during the first fraction on Monday afternoon. Daily repositioning was controlled by portal images of the largest segment of each beam. Structured baseline, end of treatment and follow up evaluation forms were used to prospectively collect toxicities and oncological outcomes at each consultation. Patient agreement for data collection and analysis was prospectively obtained. $Φg Results From February 2021 to March 2021, the 1-week breast procedure was proposed to up to 3 patients/week, >65 years, in complete resection after conservative surgery, with pT1-T3 N0 BC, without tumor bed boost or regional lymph nodes irradiation. Six out of seven patients (85.7%) accepted the 1-week breast procedure. All procedures were successfully conducted over 5 days with complete patient and RT team satisfaction. A followup of acute toxicities by online consultation on day 10, structured evaluation forms and management decision trees has been implemented for these patients. No grade >2 acute toxicities (CTACE V4.0) have been reported so far. Conclusion The successful implementation of this comprehensive 1-week breast workflow with AI based delineation and semi-automated rIMRT without PSQA demonstrates the practical feasibility of the whole procedure over 5 days reducing drastically the coming-and-going to the hospital and the overall RT management time per patient. Our work opens the way for further development of comprehensive compact workflows in various settings.

Radiotherapy and Oncology, 2021

PURPOSE To describe the quality assurance (QA) program and early toxicities in the phase III rand... more PURPOSE To describe the quality assurance (QA) program and early toxicities in the phase III randomized trial BONBIS (NCT00907868) on the role of a localized radiation boost in ductal carcinoma in situ (DCIS). MATERIALS AND METHODS From November 2008 to July 2014, 2004 patients were randomized in arm A (only whole breast radiotherapy, WBRT) and arm B (WBRT+boost). The QA program involved 44 participant centers that performed the dummy run (DR). Compliance and uniformity of clinical target volume (CTV) delineations, and dose prescription and delivery according to the BONBIS trial radiotherapy guidelines were analyzed. Acute toxicities (during and up to 3 months after radiotherapy completion, NCI-CTCAE v3.0 classification) were evaluated in 1929 patients. RESULTS The differences in whole breast CTV (CTV1) and planning target volume (PTV1) were ≤10%, and the differences in boost CTV (CTV2) and PTV (PTV2) were ≥20% compared with the reference DR values; 95% of the prescribed dose encompassed 98.7% and 100% of the median CTV1 and CTV2. Grade ≥2 breast erythema (38.3% vs. 22.4% of grade 2 and 5.4% vs. 2.1% of grade 3, p<0.001), grade ≥2 dermatitis (2.8% vs. 0.7%, p<0.001), and grade 2 hyperpigmentation (6.9% vs. 3.6%, p=0.005) were more frequent in arm B than arm A. No acute lung or cardiac toxicity was observed. Smoking history, large breast size, and large breast CTV were strong predictive factors of grade ≥2 acute skin toxicities. CONCLUSIONS The QA program showed deviations in breast and tumor bed delineation. The boost significantly increased acute skin toxicities.

Cancer/Radiothérapie, 2021

Introduction et but de l’etude Le cancer du sein inflammatoire est une entite de mauvais pronosti... more Introduction et but de l’etude Le cancer du sein inflammatoire est une entite de mauvais pronostic, representant entre 1 et 5 % des nouveaux cas de cancer du sein et correspond au stade T4d dans la derniere classification TNM. Pour les formes localisees, le traitement le plus frequemment propose est un traitement multimodal associant la chimiotherapie, la chirurgie et la radiotherapie. L’objectif de cette etude retrospective multicentrique etait d’evaluer la survie sans progression et la survie globale chez des patientes, issues de huit centres francais, atteintes d’un cancer du sein inflammatoire localise et de determiner differents facteurs pronostiques. Materiel et methodes Cette etude incluait les patientes prises en charge pour un cancer du sein inflammatoire localise (T4d, Nx, M0) entre 2010 et 2017. Les patientes ayant moins de 6 mois de suivi ont ete exclues de l’etude, sauf en cas de deces. Les taux de survie globale et de survie sans progression a 2 et 5 ans ainsi que le caractere pronostique des differents scores histologiques (Sataloff et Chevalier) ont ete determines. Resultats et analyse statistique Nous avons inclus 369 patientes atteintes d’un cancer du sein inflammatoire localise avec un âge median de 54 ± 15 ans, dont 46 (12 %) avaient plus de 70 ans. Au moment du diagnostic les patientes avaient une atteinte ganglionnaire dans 83 % des cas (57 % N1, 11 % de N2, 15 % de N3). La grande majorite des patientes ont eu une chimiotherapie premiere neoadjuvante (n = 352, 95 %), suivie d’une chirurgie (n = 325, 88 %), suivie d’une radiotherapie postoperatoire (n = 296, 80 %). Une chimiotherapie premiere neoadjuvante etait donnee chez 98 % des patientes de moins de 70 ans (n = 310) et chez 87 % des plus de 70 ans (n = 40) (p = 0,002). Seulement 32 patientes (9 %) avaient ete irradiees en situation preoperatoire, soit de maniere exclusive (n = 14, 4 %), soit de maniere concomitante a une chimiotherapie (n = 18, 5 %). Chez les patientes qui avaient recu une chimiotherapie neoadjuvante, 117 (soit 37 %) avaient eu un effet therapeutique total ou presque au niveau de la tumeur mammaire parmi les 317 patientes evaluables (TA selon Sataloff). Apres un suivi median de 50 mois (extremes : 28–74 mois), les taux de survie globale a 2 ans et 5 ans etait respectivement de 88 % (intervalle de confiance a 95 % [IC95 %] : 84–91 %] et 73 % (IC95 % : 67–78 %), tandis que les taux de survie sans progression a 2 ans et 5 ans etaient respectivement de 72 % (IC95 % : 67–76 %) et 54 % (IC95 % : 48–59 %). Un score de Sataloff TB, TC ou TD etait un facteur de risque de deces (hazard ratio [HR] : 2,1 [1,2 ;3,6], p = 0,006), de meme qu’un score de Chevalier de 2, 3 ou 4 (HR : 3,2 [1,4 ;7,3], p = 0,006). Conclusion A notre connaissance, notre etude est actuellement la plus grande serie multicentrique de patientes atteintes d’un cancer du sein inflammatoire localise. L’inclusion des patientes traitees entre 2010 et 2017 permet de refleter les pratiques therapeutiques actuelles. Malgre cela, le cancer du sein inflammatoire localise apparait encore comme une maladie de mauvais pronostic. Une mauvaise reponse histologique a la chimiotherapie neoadjuvante est dans notre etude un facteur pronostique pejoratif et invite a s’interroger sur d’eventuelles strategies d’intensification chez ces patientes.

Cancer/Radiothérapie, 2020

Cancer/Radiothérapie, 2020

Introduction et but de l’etude Plusieurs etudes de phase III randomisees ont montre la non-inferi... more Introduction et but de l’etude Plusieurs etudes de phase III randomisees ont montre la non-inferiorite de la radiotherapie hypofractionnee moderee par comparaison a l’irradiation normofractionnee en termes de survie globale, rechute locale et survenue de toxicite aigue et tardive dans le traitement adjuvant des tumeurs du sein. La radiotherapie hypofractionnee moderee est donc devenue le standard pour l’irradiation mammaire. Les donnees de vie reelle, prospectives, multicentriques et structurees pourraient contribuer a la validation des conclusions de ces essais. L’objectif de notre etude etait de comparer la toxicite aigue mammaire en vie reelle apres irradiation hypofractionnee moderee ou normofractionnee entre differents centres. Materiel et methodes Une fiche standardisee d’evaluation (FSE) prospective de la toxicite aigue a ete mise en place progressivement dans Mosaiq©. De novembre 2015 a fevrier 2020, trois centres (Gustave-Roussy, Jean-Godinot, Paul-Straus ont systematiquement complete cette fiche en fin de traitement permettant une gradation de la toxicite aigue observees selon les Common Terminology Criteria for Adverse Events (CTCAE V4). Une extraction automatique des donnees (patient, tumeur, traitement et toxicite aigue) a ensuite ete realisee. Resultats et analyse statistique Parmi 3518 patients, les dossiers de 2052 patients traites avec un complement d’irradiation du lit tumoral ont ete analyses (1343 du centre Paul-Straus [soit 65,4 %], 521 de Jean-Godinot [soit 25,4 %] et 188 de Gustave-Roussy [soit 9,2 %]) dont 645 traites par irradiation hypofractionnee moderee (majoritairement 2,67 Gy par fraction, soit 31,4 %) et 1407 par irradiation normofractionnee (soit 68,6 %). L’âge median etait de 60 ans (extremes : 24-93 ans) avec pour 97,7 % un indice de performance selon l’Organisation mondiale de la sante (OMS) de 0-1, pour 72,0 % une tumeur exprimant des recepteurs estrogeniques, 62,7 % des recepteurs a la progesterone et 9,9 % HER + + + ; majoritairement de stade T1-T2 (85,5 %), N0 (69,3 %), M0 (84,0 %). Dans chaque centre, la toxicite aigue de la radiotherapie hypofractionnee moderee n’etait pas superieure a celle de la radiotherapie normofractionnee. Apres radiotherapie hypofractionnee moderee, une difference statistiquement significative a ete observee entre les centres en termes de dermite radique de grade 2-3 (contre 0-1 ; Chi2 = 25,3 ; p Tableau 1 ). Conclusion Notre etude a mis en evidence des differences de toxicite aigue entre centres apres une irradiation mammaire avec un complement d’irradiation. Cette heterogeneite pourrait s’expliquer par des differences de population, des fluctuations d’echantillonnage, une subjectivite dans la gradation ou etre liee au traitement. La saisie prospective se poursuit, s’integrant a la pratique clinique. De nouveaux centres utilisent la fiche standardisee d’evaluation, ce qui permettra des analyses conjointes ulterieures et un suivi de la toxicite aigue.

Frontiers in Oncology, 2020

European Journal of Cancer, 2020

fraction neoadjuvant radiotherapy is under study. We sought to investigate the rate of pathologic... more fraction neoadjuvant radiotherapy is under study. We sought to investigate the rate of pathologic response and postoperative toxicities related to delaying surgery after neoadjuvant radiotherapy. Methods: Women 65 years of age or older with a new diagnosis of stage I unifocal luminal A breast cancer were eligible for inclusion. A single 20 Gy dose of radiotherapy to the primary breast tumor was given, followed by breast-conserving surgery 3 months later. The primary endpoint was the pathologic response rate assessed by microscopic evaluation using the Miller-Payne system. The secondary endpoint was the incidence of radiation toxicity, graded according to the Common Terminology Criteria for Adverse Events (CTCAE). The toxicity was planned to be assessed at 6 weeks, 4 months, 12 months and yearly for up to 5 years after radiotherapy. Results: To date, 13 patients have been successfully treated and had completed the 4-month follow-up. Median age of patients was 71 years (range: 65-83 years). Neoadjuvant radiotherapy resulted in a tumour pathologic response in 11 of 13 patients with a median residual cellularity of 1% (range: 0-10%). At the 4 months' toxicity assessment, 10 patients developed grade 1 toxicities (dermatitis, telangiectasia, fibrosis, breast pain, breast swelling and chronic mastitis), and 3 patients developed grade 2 toxicities (dermatitis, fibrosis and skin or wound infection). No grade 3 or higher toxicities were noted. Conclusion: This study demonstrates that delaying surgery after a single fraction of neoadjuvant radiotherapy can lead to a high level of pathologic response in most patients and is relatively well tolerated with acceptable toxicity. Continued follow up of our patients and subsequent larger trials are needed to better assess the late radiation toxicities as well as the optimal fractionation and timing of this novel technique in the management of earlystage breast cancer.