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BACKGROUND: Data suggest an association between positron emission tomography/CT (PET/CT) metabolic metrics and tumor microenvironment in several malignancies, and a potential role of PET/CT to monitor response to immunotherapy. OBJECTIVE: To evaluate the correlation between tumor loco-regional extension and tumor-infiltrating lymphocyte infiltration in locally advanced cervical cancer prior to concurrent chemo-radiotherapy.The secondary objective was to assess the association between tumor-infiltrating lymphocytes and PET/CT metabolic metrics. METHODS: Patients with locally advanced cervical cancer and negative para-aortic extensions on PET/CT were included. Two senior nuclear medicine physicians specializing in gynecologic oncology reviewed all PET/CT exams, and extracted tumor maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis, as well as pelvic lymph node involvement. One senior gynecologic oncology pathologist assessed intraepithelial tumor-infiltrating lymphocytes and stromal tumor-infiltrating lymphocytes. Intraepithelial tumor-infiltrating lymphocytes were categorized following previous studies as <1% and >1%. The cut-off for stromal tumor-infiltrating lymphocytes was chosen empirically: intermediate <60% and high >60%. RESULTS: 86 patients were included. Intraepithelial tumor-infiltrating lymphocytes were not significantly associated with tumor metabolic metrics. Intraepithelial tumor-infiltrating lymphocytes were not significantly associated with maximum standard uptake value (p=0.16), or metabolic tumor volume (p=0.19). Tumors with <1% intraepithelial tumor-infiltrating lymphocytes score were associated with a higher MRI tumor size (≥ median) (63.3% vs 39.3%, p=0.04). Patients with pelvic lymph node uptake were significantly more frequent in patients with high stromal tumor-infiltrating lymphocytes score (≥60%) (61.5% vs 31.7%, p=0.009). CONCLUSIONS: Poor or absent intraepithelial tumor-infiltrating lymphocytes were associated with more advanced disease at diagnosis and larger tumor size. Tumor-infiltrating lymphocytes were not associated with tumor metabolic activity. Intraepithelial and stroma tumor-infiltrating lymphocytes are not redundant and should be assessed separately. Further work is needed to evaluate the association between tumor metabolic profile and immune populations, including different T-cell subtypes for patient selection for immunotherapy strategies.
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Neoplasias de los Genitales Femeninos , Neoplasias del Cuello Uterino , Humanos , Femenino , Tomografía Computarizada por Tomografía de Emisión de Positrones , Linfocitos Infiltrantes de Tumor , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/terapia , Neoplasias del Cuello Uterino/metabolismo , Neoplasias de los Genitales Femeninos/patología , Tomografía de Emisión de Positrones , Ganglios Linfáticos/patología , Estudios Retrospectivos , Fluorodesoxiglucosa F18 , Radiofármacos , Microambiente TumoralRESUMEN
BACKGROUND: Retroperitoneal sarcomas are tumours with a poor prognosis. Upfront characterisation of the tumour is difficult, and under-grading is common. Radiomics has the potential to non-invasively characterise the so-called radiological phenotype of tumours. We aimed to develop and independently validate a CT-based radiomics classification model for the prediction of histological type and grade in retroperitoneal leiomyosarcoma and liposarcoma. METHODS: A retrospective discovery cohort was collated at our centre (Royal Marsden Hospital, London, UK) and an independent validation cohort comprising patients recruited in the phase 3 STRASS study of neoadjuvant radiotherapy in retroperitoneal sarcoma. Patients aged older than 18 years with confirmed primary leiomyosarcoma or liposarcoma proceeding to surgical resection with available contrast-enhanced CT scans were included. Using the discovery dataset, a CT-based radiomics workflow was developed, including manual delineation, sub-segmentation, feature extraction, and predictive model building. Separate probabilistic classifiers for the prediction of histological type and low versus intermediate or high grade tumour types were built and tested. Independent validation was then performed. The primary objective of the study was to develop radiomic classification models for the prediction of retroperitoneal leiomyosarcoma and liposarcoma type and histological grade. FINDINGS: 170 patients recruited between Oct 30, 2016, and Dec 23, 2020, were eligible in the discovery cohort and 89 patients recruited between Jan 18, 2012, and April 10, 2017, were eligible in the validation cohort. In the discovery cohort, the median age was 63 years (range 27-89), with 83 (49%) female and 87 (51%) male patients. In the validation cohort, median age was 59 years (range 33-77), with 46 (52%) female and 43 (48%) male patients. The highest performing model for the prediction of histological type had an area under the receiver operator curve (AUROC) of 0·928 on validation, based on a feature set of radiomics and approximate radiomic volume fraction. The highest performing model for the prediction of histological grade had an AUROC of 0·882 on validation, based on a radiomics feature set. INTERPRETATION: Our validated radiomics model can predict the histological type and grade of retroperitoneal sarcomas with excellent performance. This could have important implications for improving diagnosis and risk stratification in retroperitoneal sarcomas. FUNDING: Wellcome Trust, European Organisation for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group, the National Institutes for Health, and the National Institute for Health and Care Research Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research.
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Leiomiosarcoma , Liposarcoma , Neoplasias Retroperitoneales , Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Masculino , Femenino , Anciano , Adulto , Persona de Mediana Edad , Anciano de 80 o más Años , Leiomiosarcoma/patología , Estudios Retrospectivos , Sarcoma/patología , Liposarcoma/diagnóstico por imagen , Liposarcoma/patología , Neoplasias de los Tejidos Blandos/patología , Neoplasias Retroperitoneales/patología , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Positron emission tomography/computed tomography (PET/CT) fails to detect approximately 25% of aortic lymph node metastasis in patients with PET/CT stage IIIC1 cervical cancer. Surgical staging could lead to treatment modification and to improved para-aortic and distant control. PRIMARY OBJECTIVES: To demonstrate if chemoradiation with tailored external beam radiation field based on surgical staging and pathologic examination of the para-aortic lymph node is associated with improved 3-year disease-free survival compared with patients staged with PET/CT staging only. STUDY HYPOTHESIS: Surgical staging followed by tailored chemoradiation will improve disease-free survival while avoiding unnecessary prophylactic extended-field chemoradiation in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC1 cervical cancer. TRIAL DESIGN: This is an international multicenter, randomized, phase III study. Eligible patients will be randomized 1:1 between PET/CT staging followed by chemoradiation (control arm), or surgical staging followed by tailored chemo-radiation (experimental arm). Randomization will be stratified by tumor stage according to TNM classification, center, and adjuvant treatment. MAJOR INCLUSION/EXCLUSION CRITERIA: Main inclusion criteria are histologically proven PET/CT FIGO stage IIIC1 cervical cancer. Main exclusion criteria include unequivocal positive common iliac or para-aortic lymph node at pre-therapeutic imaging PET/CT. PRIMARY ENDPOINTS: The primary endpoint is disease-free survival defined as the time from randomization until first relapse (local, regional, or distant), or death from any cause. SAMPLE SIZE: 510 eligible patients ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: The estimated date for completing accrual will be Q2 2027. The estimated date for presenting results will be Q4 2030. TRIAL REGISTRATION NUMBER: NCT05581121.
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Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/cirugía , Neoplasias del Cuello Uterino/patología , Metástasis Linfática/patología , Recurrencia Local de Neoplasia/patología , Escisión del Ganglio Linfático/métodos , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/patología , Estadificación de Neoplasias , Estudios RetrospectivosRESUMEN
BACKGROUND: To assess the impact of PET/CT functional parameters on survival, locoregional, and distant failure according to the most distant level of lymph node [18F]FDG uptake in patients with locally advanced cervical cancer (LACC). METHODS: Retrospective study including 148 patients with LACC treated with concurrent chemoradiotherapy after PET/CT and para-aortic lymph node (PALN) surgical staging. Two senior nuclear medicine physicians reviewed all PET/CT exams and retrieved tumor and lymph node metabolic parameters: SUVmax, MTV, TLG. Oncological outcomes according to metabolic parameters and level of lymph node spread on PET/CT were assessed. RESULTS: In patients without lymph node uptake on PET/CT, high MTV values of the cervical tumor were associated with DFS (HR = 5.14 95%CI = [2.15-12.31]), OS (HR = 6.10 95%CI = [1.89-19.70]), and time to distant (HR = 4.73 95%CI = [1.55-14.44]) and locoregional recurrence (HR = 5.18 95%CI = [1.72-15.60]). In patients with pelvic lymph node (PLN) uptake but without PALN uptake on [18F]FDG-PET/CT, high MTV values of the cervical tumor were associated with DFS (HR = 3.17 95%CI = [1.02-9.83]) and OS (HR = 3.46 95%CI = [0.96-12.50]), and the number of PLN fixations was associated with DFS (HR = 1.30 95%CI = [1.10-1.53]), OS (HR = 1.35 95%CI = [1.11-1.64]), and time to distant (HR = 1.35 95%CI = [1.08-1.67]) and locoregional recurrence (HR = 1.31 95%CI = [1.08-1.59]). There was no significant association between cervical tumor metabolic or lymph node metrics and survival outcome in patients with PALN uptake. CONCLUSIONS: Cervical MTV is more accurate than SUVmax to predict survival outcome in patients with locoregional disease confined to the pelvis and should be implemented in routine clinical practice. Prognostic value of metabolic metrics disappears with PALN uptake, which is associated with distant failure in nearly half of patients.
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Fluorodesoxiglucosa F18 , Neoplasias del Cuello Uterino , Femenino , Fluorodesoxiglucosa F18/metabolismo , Humanos , Ganglios Linfáticos/patología , Recurrencia Local de Neoplasia/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía de Emisión de Positrones , Pronóstico , Radiofármacos/metabolismo , Estudios Retrospectivos , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/terapiaRESUMEN
PURPOSE: Women's sexual health and wellbeing with cervical or vaginal cancer may be largely affected by complications from external beam radiotherapy (EBRT) and utero-vaginal brachytherapy (BT), of which vaginal stenosis is the main complication. The objective of this study was to assess the impact of support by a nurse sexologist on sexuality, vaginal side-effects, and the quality of clinical follow-up in patients treated with brachytherapy for cervical or vaginal cancer. METHODS: We performed a retrospective study of the sexuality of women treated for cervical or vaginal cancer. Data from patients with cervical or vaginal cancer who underwent brachytherapy between 2013 and 2017 were collected at Institut Universitaire de Cancer de Toulouse-Oncopôle (IUCT-Oncopôle). Patients were divided into two groups: group A (intervention group) received support from a nurse sexologist and group B (control group) did not. The chi-square test and a logistic multivariate model were used for data analysis. RESULTS: A total of 156 patients were included in this study, including 57.7% who were followed by a nurse sexologist. We observed low compliance in using vaginal dilators after brachytherapy and/or radiotherapy over time regardless of the group, and patients' sexual activity was inadequately addressed. Information regarding the resumption of sexuality 2 months after treatment was missing in 1.1% of patients in group A and in 36.4% of patients in group B. Multivariate analysis showed that patients in group A had a lower risk of developing vaginal stenosis with OR crude = 0.5 (95% CI = 0.25-0.92) and OR adj. = 0.5 (95% CI = 0.26-1.09) compared with those in group B. CONCLUSION: This retrospective study highlights the lack of information collected by physicians during follow-up concerning the sexuality of patients with cervical or vaginal cancer treated by EBRT and BT. The support offered by nurse sexologists in improving patients' sexual activity and reducing their physical side-effects such as vaginal stenosis is likely to be beneficial. A prospective study is currently being conducted to validate the present findings.
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Braquiterapia/efectos adversos , Sistemas de Apoyo Psicosocial , Conducta Sexual/psicología , Sexualidad/estadística & datos numéricos , Neoplasias del Cuello Uterino/radioterapia , Neoplasias Vaginales/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma in Situ/radioterapia , Constricción Patológica/epidemiología , Constricción Patológica/etiología , Dilatación , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Enfermeras y Enfermeros , Cooperación del Paciente , Estudios Prospectivos , Estudios Retrospectivos , Sexología/métodosRESUMEN
BACKGROUND: Pathological complete response to preoperative treatment in adults with soft-tissue sarcoma can be achieved in only a few patients receiving radiotherapy. This phase 2-3 trial evaluated the safety and efficacy of the hafnium oxide (HfO2) nanoparticle NBTXR3 activated by radiotherapy versus radiotherapy alone as a pre-operative treatment in patients with locally advanced soft-tissue sarcoma. METHODS: Act.In.Sarc is a phase 2-3 randomised, multicentre, international trial. Adults (aged ≥18 years) with locally advanced soft-tissue sarcoma of the extremity or trunk wall, of any histological grade, and requiring preoperative radiotherapy were included. Patients had to have a WHO performance status of 0-2 and a life expectancy of at least 6 months. Patients were randomly assigned (1:1) by an interactive web response system to receive either NBTXR3 (volume corresponding to 10% of baseline tumour volume at a fixed concentration of 53·3âg/L) as a single intratumoural administration before preoperative external-beam radiotherapy (50 Gy in 25 fractions) or radiotherapy alone, followed by surgery. Randomisation was stratified by histological subtype (myxoid liposarcoma vs others). This was an open-label study. The primary endpoint was the proportion of patients with a pathological complete response, assessed by a central pathology review board following European Organisation for Research and Treatment of Cancer guidelines in the intention-to-treat population full analysis set. Safety analyses were done in all patients who received at least one puncture and injection of NBTXR3 or at least one dose of radiotherapy. This study is registered with ClinicalTrials.gov, number NCT02379845, and is ongoing for long-term follow-up, but recruitment is complete. FINDINGS: Between March 3, 2015, and Nov 21, 2017, 180 eligible patients were enrolled and randomly assigned and 179 started treatment: 89 in the NBTXR3 plus radiotherapy group and 90 in the radiotherapy alone group. Two patients in the NBTXR3 group and one patient in the radiotherapy group were excluded from the efficacy analysis because they were subsequently discovered to be ineligible; thus, a total of 176 patients were analysed for the primary endpoint in the intention-to-treat full analysis set (87 in the NBTXR3 group and 89 in the radiotherapy alone group). A pathological complete response was noted in 14 (16%) of 87 patients in the NBTXR3 group and seven (8%) of 89 in the radiotherapy alone group (p=0·044). In both treatment groups, the most common grade 3-4 treatment-emergent adverse event was postoperative wound complication (eight [9%] of 89 patients in the NBTXR3 group and eight [9%] of 90 in the radiotherapy alone group). The most common grade 3-4 adverse events related to NBTXR3 administration were injection site pain (four [4%] of 89) and hypotension (four [4%]) and the most common grade 3-4 radiotherapy-related adverse event was radiation skin injury in both groups (five [6%] of 89 in the NBTXR3 group and four [4%] of 90 in the radiotherapy alone group). The most common treatment-emergent grade 3-4 adverse event related to NBTXR3 was hypotension (six [7%] of 89 patients). Serious adverse events were observed in 35 (39%) of 89 patients in the NBTXR3 group and 27 (30%) of 90 patients in the radiotherapy alone group. No treatment-related deaths occurred. INTERPRETATION: This trial validates the mode of action of this new class of radioenhancer, which potentially opens a large field of clinical applications in soft-tissue sarcoma and possibly other cancers. FUNDING: Nanobiotix SA.
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Hafnio/uso terapéutico , Nanopartículas/uso terapéutico , Óxidos/uso terapéutico , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Sarcoma/terapia , Neoplasias de los Tejidos Blandos/terapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radioterapia/métodos , Adulto JovenRESUMEN
PURPOSE: The aim of this study was to retrospectively study survival and long-term morbidities of children with nasopharyngeal carcinoma (NPC) treated by induction chemotherapy and concurrent chemoradiation (CRT). The total dose of radiation was adapted to the response following neoadjuvant chemotherapy. METHODS: Children with non-metastatic NPC treated in France between 1999 and 2015 were retrospectively included in the study. The strategy combined neoadjuvant platinum-based chemotherapy, followed by adapted CRT to tumor response. RESULTS: In total, 95 patients (median age 15 years [range, 7-23 years], male-to-female ratio 1.8) with undifferentiated NPC were included; 59% of patients had TNM stage IV. Intensity-modulated radiotherapy (IMRT) was delivered to 57 patients (60%), while the other patients were treated with conformal RT (3D-RT). After a median follow-up of 4.5 years [range, 3.6-5.5 years], 13 relapses and seven deaths had occurred. The 3year overall and relapse-free survival (RFS) were 94% [95% CI, 85-97%] and 86% [77-92%], respectively. The locoregional failure rate was 6% [95% CI, 2-14]. Long-term treatment-related sequelae of grade 2+ were reported by 37 (50%) patients; odynophagia was significantly reduced treated by IMRT vs. conventional 3D-RT (7% vs. 55%, pâ¯= 0.015). Using a reduction dose of 59.4â¯Gy, 54â¯Gy, and 45â¯Gy, respectively, to the primary, involved, and uninvolved neck nodes, after a favorable tumor response, was not associated with an increased locoregional failure rate. CONCLUSIONS: The survival rates for NPC have been considerably improved by means of multimodal therapy, but long-term locoregional morbidity remains common. Use of IMRT may induce less residual odynophagia. Radiation dose reduction adapted to chemotherapy response does not have a negative impact on outcome. These findings support the use of an RT protocol adapted to the tumor response to neoadjuvant chemotherapy for a long-lasting improvement in the patient's quality of life.
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Quimioradioterapia/métodos , Quimioterapia de Inducción , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia , Adolescente , Niño , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Francia , Humanos , Masculino , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/patología , Estadificación de Neoplasias , Radioterapia de Intensidad Modulada , Estudios Retrospectivos , Insuficiencia del Tratamiento , Adulto JovenRESUMEN
PURPOSE: Aim of the study was to assess impact of pretherapeutic FDG-PET/CT metabolic parameters on response to chemoradiotherapy (CRT) and survival in locally advanced cervical cancer (LACC) patients without paraaortic lymph node involvement. METHODS: LACC patients treated with CRT without macrometastatic involvement after paraaortic surgical staging were included. All patients had received at least 45 Gy radiotherapy and five cycles of platinum-based chemotherapy. High-risk histologies were excluded. Two senior nuclear physician experts in gynaecologic oncology reviewed all PET/CT exams, and extracted tumor SUVmax, MTV, and TLG (standardized uptake value, metabolic tumor volume, and total lesion glycolysis respectively). Response to CRT was assessed with a pelvic MRI done after 45 Gy. Medical charts were reviewed for clinical, pathology, and survival data. RESULTS: Ninety-three patients were included in the study. The overall survival (OS) rates at 2 and 5 years were 83.0% [95%CI: 72.5-89.8] and 71.2% [57.5-81.2] respectively. The RFS rates at 2 and 5 years were 72.5% [61.5-80.9] and 64.4% [52.3-74.2] respectively. Higher cervical SUVmax and TLG were significantly associated with poor response to CRT. In multivariate analysis, cervical SUVmax was the main predictive factor for OS. CONCLUSION: Cervical tumor SUVmax was demonstrated to be a non-invasive prognostic biomarker for response to treatment and survival in LACC patients without paraaortic involvement. SUVmax and other PET/CT metabolic parameters require further prospective investigation to help tailoring of local treatment.
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Aorta/patología , Quimioradioterapia , Ganglios Linfáticos/patología , Metástasis Linfática , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/terapia , Adulto , Anciano , Biomarcadores de Tumor , Supervivencia sin Enfermedad , Femenino , Fluorodesoxiglucosa F18 , Humanos , Persona de Mediana Edad , Análisis Multivariante , Metástasis de la Neoplasia , Tomografía Computarizada por Tomografía de Emisión de Positrones , Pronóstico , Radiofármacos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: Tumor volume and regression after external beam radiotherapy have been shown to be accurate parameters to assess treatment response via magnetic resonance imaging (MRI). The aim of the study was to evaluate the prognostic value of tumor size reduction rate after external beam radiotherapy and chemotherapy prior to brachytherapy. METHODS: Patients with locally advanced cervical cancer treated at two French comprehensive cancer centers between 1998 and 2010 were included. Treatment was pelvic external beam radiotherapy with platinum based chemotherapy followed by brachytherapy. Records were reviewed for demographic, clinical, imaging, treatment, and follow-up data. Anonymized linked data were used to ascertain the association between pre-external and post-external beam radiotherapy MRI results, and survival data. RESULTS: 185 patients were included in the study. Median age at diagnosis was 45 years (range 26-72). 77 patients (41.6%) were International Federation of Gynecology and Obstetrics stage IB2-IIA disease and 108 patients (58.4%) were stage IIB-IVA. Median tumor size after external beam radiotherapy and chemotherapy was 2.0 cm (range 0.0-8.0) and median tumor size reduction rate was 62.4% (range 0.0-100.0%). Tumor size and tumor reduction rate at 45 Gy external beam radiotherapy MRI were significantly associated with local recurrence free survival (P<0.001), disease free survival, and overall survival (P<0.05). Tumor reduction rate ≥60% was significantly associated with a decreased risk of relapse and death (HR (95% CI) 0.21 (0.09 to 0.50), P=0.001 for local recurrence free survival; 0.48 (0.30 to 0.77) P=0.002 for disease free survival; and 0.51 (0.29 to 0.88), P=0.014 for overall survival). CONCLUSIONS: Tumor size reduction rate >60% between pre-therapeutic and post-therapeutic 45 Gy external beam radiotherapy with concurrent chemotherapy was associated with improved survival. Future studies may help to identify patients who may ultimately benefit from completion surgery, adjuvant chemotherapy, and closer follow-up.
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Recurrencia Local de Neoplasia/patología , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/terapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Braquiterapia , Quimioradioterapia , Supervivencia sin Enfermedad , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/radioterapiaRESUMEN
BACKGROUND: Providing early and better care in onco-sexuality and a better understanding of the sexual health care needs of patients before they start treatment is required. OBJECTIVE: To assess sexual quality of life and need for sexology care of patients when they are starting radiotherapy. DESIGN: We performed a cross-sectional study of adult patients with cancer admitted for radiotherapy treatment in a regional comprehensive cancer center. METHODS: We selected all consecutive adult patients scheduled to start radiotherapy within a 3-month period and excluded patients who could not complete the questionnaires. Patients were asked to complete the Sexual Quality of Life Questionnaire (SQoL) and a needs-assessment questionnaire. OUTCOMES: Total score on the SQoL and willingness (yes or no) to get help for a sexual problem. RESULTS: The study sample was composed of 77 men and 123 women. The average SQoL scores were 68.4 ± 20.9 and 47.1 ± 13.0 for men and women, respectively (P < .001). Of sexually active patients, 58% had decreased frequency of intercourse or had completely stopped sexual activity after their cancer diagnosis. Half the participants wanted care for their sexual concerns. The proportion desiring specific types of care varied from 28.5% (couple counseling) to 54.5% (sexual physician) with variation by sex or type of cancer. Furthermore, 11.5% of participants declared their willingness to join support groups. CLINICAL IMPLICATIONS: Early interventions before radiotherapy could improve sexual quality of life, particularly in women. STRENGTHS AND LIMITATIONS: Strengths are the SQoL validated in men and women, the original window for assessment, and the study location. Limitations are the monocentric design, the potential recall bias for data before cancer diagnosis, and the fact that some patients had treatments before radiotherapy. CONCLUSION: Our data suggest the need to examine the sexual health trajectory in a prospective fashion from diagnosis to survivorship. Almont T, Delannes M, Ducasson A, et al. Sexual Quality of Life and Needs for Sexology Care of Cancer Patients Admitted for Radiotherapy: A 3-Month Cross-Sectional Study in a Regional Comprehensive Reference Cancer Center. J Sex Med 2017;14:566-576.
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Neoplasias/psicología , Calidad de Vida/psicología , Conducta Sexual/psicología , Disfunciones Sexuales Fisiológicas/psicología , Disfunciones Sexuales Psicológicas/psicología , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/radioterapia , Estudios Prospectivos , Radioterapia/efectos adversos , Disfunciones Sexuales Fisiológicas/etiología , Disfunciones Sexuales Psicológicas/etiología , Encuestas y Cuestionarios , SobrevivientesRESUMEN
INTRODUCTION: Neuroblastoma (NB) is the most frequent indication for extracranial pediatric radiotherapy. As long-term survival of high-risk localized NB has greatly improved, we reviewed treatment-related late toxicities in pediatric patients who received postoperative radiotherapy (RT) for localized NB within two French prospective clinical trials: NB90 and NB94. PATIENTS AND METHODS: From 1990-2000, 610 children were enrolled. Among these, 35 were treated with induction chemotherapy, surgery, and RT. The recommended RT dose was 24 Gy at ≤ 2 years, 34 Gy at > 2 years, ± a 5 Gy boost in both age groups. RESULTS: The 22 patients still alive after 5 years were analyzed. The median follow-up time was 14 years (range 5-21 years). Late effects after therapy occurred in 73 % of patients (16/22), within the RT field for 50 % (11/22). The most frequent in-field effects were musculoskeletal abnormalities (n = 7) that occurred only with doses > 31 Gy/1.5 Gy fraction (p = 0.037). Other effects were endocrine in 3 patients and second malignancies in 2 patients. Four patients presented with multiple in-field late effects only with doses > 31 Gy. CONCLUSION: After a median follow-up of 14 years, late effects with multimodality treatment were frequent. The most frequent effects were musculoskeletal abnormalities and the threshold for their occurrence was 31 Gy.
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Neuroblastoma/radioterapia , Traumatismos por Radiación/etiología , Radioterapia Adyuvante , Adolescente , Niño , Preescolar , Fraccionamiento de la Dosis de Radiación , Femenino , Francia , Amplificación de Genes , Humanos , Lactante , Masculino , Proteína Proto-Oncogénica N-Myc , Neoplasia Residual/mortalidad , Neoplasia Residual/radioterapia , Neoplasias Inducidas por Radiación/etiología , Neuroblastoma/genética , Neuroblastoma/mortalidad , Proteínas Nucleares/genética , Proteínas Oncogénicas/genética , Estudios Prospectivos , Dosificación Radioterapéutica , Análisis de SupervivenciaRESUMEN
Objective: As craniospinal irradiation (CSI) is delivered more frequently by helical tomotherapy (HT) with few reports about late effects, we analysed all patients treated in our centre over an 11-year period. Methods and materials: Our study included all patients that underwent CSI by HT, between September 2009 and January 2020, in the Department of Radiation Oncology of the Toulouse Cancer Institute. Acute radiotherapy toxicities were reported and medium- to long-term outcomes analysed. Results: Among the 79 patients included, 70.9 % were younger than 18 years at diagnosis, the median age was 13 (range: 1-52) at the time of radiation therapy, 67.1 % of patients had medulloblastoma. Half of them (49.4 %) had a metastatic disease at diagnosis. The median dose of CSI was 36 Gy (range, 18-36). Seventy-seven patients received a radiation boost to the original location of the primary tumour (97.5 %), 32 patients also received a boost to their metastatic sites (40.5 %). Median follow-up was 55.5 months (95 %CI = [41.2; 71.8]). The 3-year event-free survival rate was 66.3 % (95 %CI = [54.2; 75.9]). Most patients presented with acute haematological toxicities during CSI (85.9 %), predominantly severe thrombocytopenia (39.7 %). Among the 64 patients assessed for medium- and long-term outcomes, 52 survived and 47 were alive and disease-free at the latest follow-up visit on record. There were 3.8 % secondary tumours: two meningiomas and one diffuse intrinsic pontine glioma. Adult and paediatric patients respectively presented with secondary cataract (4.3 % vs 22.0 %), persistent hearing disorders (26.1 % vs 29.3 %), pulmonary or cardiac late effects (4.3 % vs 2.4 %), hormonal pituitary gland deficiencies (30.0 % vs 56.8 %) and psycho-cognitive disorders (56.5 % vs 53.7 %). Conclusion: CSI dispensed by HT, did not result in any additional acute or late toxicities when compared to 3D-CSI. There was no increase in the secondary tumour rate compared to that reported in the literature.
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While treatment of localized cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) is based on surgery, brachytherapy, which delivers a high dose of radiation to tumor tissue while sparing healthy tissue, is an alternative. Since the withdrawal of iridium wires from the market, brachytherapy has mainly been performed with high-dose-rate iridium-192 (HDR). This study evaluated the efficacy of HDR brachytherapy in terms of local control, survival, toxicity, and quality of life in patients with facial periorificial cutaneous SCC or BCC treated in our center between 2015 and 2021. Sixty-seven patients were treated for SCC (n = 49) or BCC (n = 18), on the nose (n = 29), lip (n = 28), eyelid (n = 7), or ear (n = 3). The majority had Tis or T1 tumors (73.1%). After a median follow-up of 28 months, 8 patients had a local recurrence. The local control rate at 3 years was 87.05% (95% CI 74.6-93.7). All patients developed grade 1-2 acute radio-mucositis or radiodermatitis and one experienced reversible grade 3 acute radio-mucositis. Of the 27 patients who completed the quality-of-life questionnaire, 77.8% recommended the treatment. This study confirms that HDR brachytherapy for facial cutaneous carcinomas provides good local control, good tolerance, and satisfactory functional outcome.
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PURPOSE: Memory is one of the main specific cognitive domains impaired with attention and processing speed after a pediatric brain tumor. This work explored the long-term impact of radiotherapy in children with posterior fossa tumor (PFT) on brain connectivity in neural circuits involved in memory using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: A total of 20 irradiated and 15 non-irradiated PFT survivors, and 21 healthy controls, prospectively included in the IMPALA study (NCT04324450), performed memory tests assessing episodic, procedural, and working memories and were subjected to an rs-fMRI. We manually contoured main structures involved in memory to explore connectivity at rest in a seed-to-voxel analysis. The groups were compared and differences in connectivity were correlated with behavioral scores and irradiation doses. RESULTS: The performance of all mnesic tasks was lower in PFT survivors with a greater alteration in working and episodic memory in irradiated patients. Irradiated survivors had atypical connectivities in all memory circuits compared to controls and in cortico-caudate and cortico-cerebellar circuits compared to non-irradiated survivors. Non-irradiated survivors had only atypical connectivities in the cortico-cerebellar circuits compared to controls. In irradiated survivors, atypical connectivities in cortico-hippocampal circuits were linked with episodic memory scores and dose of irradiation to the left hippocampus and in cortico-striatal circuits with procedural memory scores and dose of irradiation to the striatum. CONCLUSION: The results of this study highlight that irradiation has a long-term impact on brain connectivity in brain circuits involved in memory after pediatric PFT with a specific radiation-dose effect in supratentorial structures.
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Neoplasias Encefálicas , Neoplasias Infratentoriales , Niño , Humanos , Atención , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/patología , Neoplasias Infratentoriales/diagnóstico por imagen , Neoplasias Infratentoriales/radioterapia , Neoplasias Infratentoriales/patología , Imagen por Resonancia Magnética , Memoria a Corto Plazo , Estudios Prospectivos , Estudios de Casos y ControlesRESUMEN
BACKGROUND AND PURPOSE: Ependymoma is the third most frequent childhood braintumor. Standard treatment is surgery followed by radiation therapy including proton therapy (PBT). Retrospective studies have reported higher rates of brainstem injury after PBT than after photon therapy (XRT). We report a national multicenter study of the incidence of brainstem injury after XRT versus PBT, and their correlations with dosimetric data. MATERIAL AND METHODS: We included all patients aged < 25 years who were treated with PBT or XRT for intracranial ependymoma at five French pediatric oncology reference centers between 2007 and 2020. We reviewed pre-irradiation MRI, follow-up MRIs over the 12 months post-treatment and clinical data. RESULTS: Of the 83 patients, 42 were treated with PBT, 37 with XRT, and 4 with both (median dose: 59.4 Gy, range: 5360). No new or progressive symptomatic brainstem injury was found. Four patients presented asymptomatic radiographic changes (punctiform brainstem enhancement and FLAIR hypersignal), with median onset at 3.5 months (range: 3.09.4) after radiation therapy, and median offset at 7.6 months (range: 3.77.9). Two had been treated with PBT, one with XRT, and one with mixed XRT-PBT. Prescribed doses were 59.4, 55.8, 59.4 and 54 Gy. CONCLUSION: Asymptomatic radiographic changes occurred in 4.8% of patients with ependymoma in a large national series. There was no correlation with dose or technique. No symptomatic brainstem injury was identified.
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Neoplasias Encefálicas , Tronco Encefálico , Ependimoma , Terapia de Protones , Humanos , Ependimoma/radioterapia , Ependimoma/diagnóstico por imagen , Terapia de Protones/efectos adversos , Estudios Retrospectivos , Femenino , Masculino , Niño , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/diagnóstico por imagen , Adolescente , Preescolar , Tronco Encefálico/efectos de la radiación , Tronco Encefálico/diagnóstico por imagen , Adulto Joven , Francia , Fotones/uso terapéutico , Fotones/efectos adversos , Traumatismos por Radiación/etiología , Imagen por Resonancia Magnética , Lactante , Dosificación RadioterapéuticaRESUMEN
PURPOSE: To evaluate efficacy and feasibility of high-dose intensity-modulated radiotherapy (RT) with pre-operative helical tomotherapy, delivering 54 Gy/30 fractions in patients with retroperitoneal liposarcomas (RPLS). MATERIALS AND METHODS: Patients with operable, biopsy-proven, RPLS were included in this phase II multicenter study (ClinicalTrials.gov: NCT01841047). The primary objectives were to analyze loco-regional relapse free survival (LRFS), overall survival (OS) and toxicities, graded according to CTCAE V3.0. RESULTS: From April 2009 to September 2013, 48 patients were included. Histological types were: 20 well differentiated and 28 dedifferentiated liposarcomas. Median clinical target volume (CTV) was 2570 cc (range, 230-8734 cc). The radio-surgical schedule was completed as planned in all patients apart from one. A monobloc wide excision was achieved for all patients. Surgical margins were R0 (16; 34%), R1 (28; 60%), R2 (2; 4%) or missing (1, 2%).With a median follow-up of 5.5 years, 3-year LRFS rate was 74.2% (95%CI: [59.1%; 84.5%]). At 5 years, cumulative incidence of loco-regional relapse for well differentiated and dedifferentiated RPLS was 10% and 18%, respectively. The 5-year OS was 73.9% [95%CI: 58.7-84.3%]. During RT, the most common grade 3-4 adverse events were hematological (N = 20; 41.6%). After surgery and during follow-up, 17 patients (35.4%) presented a grade 3-4 toxicity. Two patients (4.1%) died due to a duodenal toxicity. Nine second cancers were observed. CONCLUSION: From this phase II trial of preoperative RT in RPLS patients, the dose level proposed cannot be considered safe, leading to non-negligible toxicity and second cancers rates. Our results, combined with STRASS-1 study, suggest that the ideal indication of RT for patients with RPLS still remains to be determined.
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Liposarcoma , Neoplasias Primarias Secundarias , Radioterapia de Intensidad Modulada , Humanos , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodos , Neoplasias Primarias Secundarias/etiología , Recurrencia Local de Neoplasia/patología , Liposarcoma/radioterapia , Liposarcoma/cirugía , Liposarcoma/etiologíaRESUMEN
French recommendations for clinical practice, Nice/Saint-Paul-de-Vence 2022-2023: Management of advanced cervical cancer The prognosis of cervical cancer remained pejorative until recently, first-line treatment consisting of platinum-based chemotherapy, associated with bevacizumab whenever possible, without any other therapeutic innovation for several years. However in 2022, immunotherapy appeared in the therapeutic landscape. Pembrolizumab can now be prescribed, thanks to the early access status granted by the HAS in September 2022, in patients with PD-L1 positive tumors. In parallel, bevacizumab generic is now reimbursed, allowing its association with chemotherapy on top of pembrolizumab, if indicated. For patient relapsing after platinium salts, and who never received immunotherapy, cemiplimab could be delivered and reimboursed since spring 2023, whatever could be PD-L1 status. Pretherapeutic work-up includes imaging combining MRI and PET/CT or CT of the chest, abdomen and pelvis, as well as evaluation of PD-L1 status on tumor and immune cells to define the CPS score that will determine eligibility to pembrolizumab treatment (CPS > 1). Possibilities of locoregional treatment depend on individual situations and are discussed on a case-by-case basis in multidisciplinary meetings. Early supportive care is always recommended and inclusion in clinical trials must be systematically considered.
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BACKGROUND: Using adaptive radiotherapy (ART), to determine objective clinical criteria that identify extremity soft tissue sarcoma (ESTS) patients requiring adaptation of their preoperative radiotherapy (RT) plan. PATIENTS AND METHODS: We included 17 patients with a lower extremity ESTS treated between 2019 and 2021 with preoperative RT, using helicoidal intensity-modulated RT (IMRT) tomotherapy, before surgical resection. We collected clinical, tumor parameters and treatment data. Repositioning was ascertained by daily Megavoltage computed tomography (MVCT) imaging. Using the PreciseART technology we retrospectively manually delineated at least one MVCT for each patient per week and recorded volume and dosimetric parameters. A greater than 5% change between target volume and planned target volume (PTV) dosimetric coverage from the initial planning CT scan to at least one MVCT was defined as clinically significant. RESULTS: All 17 patients experienced significant tumor volume changes during treatment; 7 tumors grew (41%) and 10 shrank (59%). Three patients (18%), all undifferentiated pleomorphic sarcomas (UPS) with increased volume changes, experienced significant reductions in tumor dose coverage. Seven patients required a plan adaptation, as determined by practical criteria applied in our departmental practice. Among these patients, only one ultimately experienced a significant change in PTV coverage. Three patients had a PTV decrease of coverage. Among them, 2 did not receive plan adaptation according our criteria. None of the patients with decreased tumor volumes had reduced target volume coverage. Monitoring volume variations by estimating gross tumor volume (GTV) on MVCT, in addition to axial and sagittal linear tumor dimensions, appeared to be most effective for detecting reductions in PTV coverage throughout treatment. CONCLUSIONS: Variations in ESTS volume are evident during preoperative RT, but significant dosimetric variations are rare. Specific attention should be paid to grade 2-3 UPSs during the first 2 weeks of treatment. In the absence of dedicated software in routine clinical practice, monitoring of tumor volume changes by estimating GTV may represent a useful strategy for identifying patients whose treatment needs to be replanned.
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Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Dosificación Radioterapéutica , Carga Tumoral , Estudios Retrospectivos , Planificación de la Radioterapia Asistida por Computador/métodos , Sarcoma/diagnóstico por imagen , Sarcoma/radioterapia , Sarcoma/cirugía , Neoplasias de los Tejidos Blandos/diagnóstico por imagen , Neoplasias de los Tejidos Blandos/radioterapia , Neoplasias de los Tejidos Blandos/cirugía , Extremidades/diagnóstico por imagen , Extremidades/patologíaRESUMEN
PURPOSE: Half of the children and adolescents treated for intracranial ependymoma experience recurrences that are not managed in a standardized manner. This study aimed to retrospectively evaluate recurrence treatments. METHODS AND MATERIALS: We assessed overall survival (OS) and progression-free survival (PFS) after a first relapse in a population of patients from the Pediatric Ependymoma Photons Protons and Imaging study (PEPPI study) who were treated with surgery and radiation therapy in French Society of Childhood Cancer reference centers between 2000 and 2013. Data were analyzed using the Cox model as well as a landmark analysis at 4 months that accounted for the guarantee-time bias. RESULTS: The median follow-up of the whole population of 202 patients was 105.1 months, with a 10-year OS of 68.2% and PFS of 45.5%. Among the 100 relapse cases, 68.0% were local relapses, 20.0% were metastatic, and 12.0% were combined (local and metastatic). Relapses were treated by surgery (nâ¯=â¯79) and/or reirradiation (nâ¯=â¯52) and/or chemotherapy (nâ¯=â¯22). The median follow-up after relapse was 77.8 months. The OS and PFS at 5 years were 43.1% and 16.2%, respectively. After surgery or radiation therapy of the first relapse, OS and PFS were more favorable, whereas treatments that included chemotherapy with or without focal treatment were associated with worse OS and PFS. In the multivariate analysis, stereotactic hypofractionated reirradiation after surgery was associated with a significantly better outcome (OS, Pâ¯=â¯.030; PFS, Pâ¯=â¯.008) and chemotherapy with a worse outcome (OS, Pâ¯=â¯.028; PFS, Pâ¯=â¯.033). CONCLUSIONS: This analysis of relapse treatments within the PEPPI study determined that irrespective of whether the relapse was localized or metastatic, treatments that included surgery and/or reirradiation had better outcomes.
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Neoplasias Encefálicas , Ependimoma , Niño , Humanos , Adolescente , Estudios Retrospectivos , Recurrencia Local de Neoplasia , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/tratamiento farmacológico , Modelos de Riesgos ProporcionalesRESUMEN
INTRODUCTION: Limb-sparing surgery combined with radiation has become the standard treatment for soft tissue sarcomas. Despite the many advantages of reconstruction procedures, such as muscle-sparing flap and local reconstruction, the use of pedicled perforator flaps remains non-consensual due to doubts about their reliability when associated with radiotherapy. This study evaluated their surgical reliability in reconstructive surgery for limb and trunk soft tissue sarcomas, in terms of healing time, wound disorders, and postoperative complications, regardless of radiation timing. PATIENTS AND METHODS: We realized a retrospective, observational, bi-center study (Cancer University Institute of Toulouse Oncopole, France and Bergonié Institute Bordeaux, France) and describes pedicled perforator flaps performed between January 2015 and January 2021. RESULTS: A total of 74 flaps were included. The median age of the population was 70-year-old. The group consisted of 68.8% (n = 51/74) propeller flaps. We found a partial necrosis rate of 28.4% (n = 21/74), scar disunion of 48.6% (n = 36/74), local infection of 10.8% (n = 8/74), and venous congestion of 13.5% (n = 10/74). Only 16.2% (n = 12/74) required secondary surgical repair to a local complication. The average length of stay was 7.3 days [1.0-25.0]. The mean operating time of our flaps was 133.4 min [38.0-280.0]. CONCLUSIONS: Pedicled perforator flaps are a surgical technique that can be used in reconstructive surgery for limb and trunk soft tissue sarcomas in adults, regardless of radiation timing. However, these flaps carry a high rate of postoperative complications so they should be reserved for expert surgeons in referral centers.