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BACKGROUND: Hypofractionated stereotactic radiotherapy (hFSRT) is a salvage option for recurrent glioblastoma (GB) which may synergize anti-PDL1 treatment. This phase I study evaluated the safety and the recommended phase II dose of anti-PDL1 durvalumab combined with hFSRT in patients with recurrent GB. METHODS: Patients were treated with 24 Gy, 8 Gy per fraction on days 1, 3, and 5 combined with the first 1500 mg Durvalumab dose on day 5, followed by infusions q4weeks until progression or for a maximum of 12 months. A standard 3 + 3 Durvalumab dose de-escalation design was used. Longitudinal lymphocytes count, cytokines analyses on plasma samples, and magnetic resonance imaging (MRI) were collected. RESULTS: Six patients were included. One dose limiting toxicity, an immune-related grade 3 vestibular neuritis related to Durvalumab, was reported. Median progression-free interval (PFI) and overall survival (OS) were 2.3 and 16.7 months, respectively. Multi-modal deep learning-based analysis including MRI, cytokines, and lymphocytes/neutrophil ratio isolated the patients presenting pseudoprogression, the longest PFI and those with the longest OS, but statistical significance cannot be established considering phase I data only. CONCLUSION: Combination of hFSRT and Durvalumab in recurrent GB was well tolerated in this phase I study. These encouraging results led to an ongoing randomized phase II. (ClinicalTrials.gov Identifier: NCT02866747).
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Neoplasias Encefálicas , Glioblastoma , Radiocirurgia , Reirradiação , Humanos , Glioblastoma/tratamento farmacológico , Glioblastoma/radioterapia , Resultado do Tratamento , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/radioterapia , Radiocirurgia/efeitos adversos , CitocinasRESUMO
PURPOSE: To develop machine learning models to predict para-aortic lymph node (PALN) involvement in patients with locally advanced cervical cancer (LACC) before chemoradiotherapy (CRT) using 18F-FDG PET/CT and MRI radiomics combined with clinical parameters. METHODS: We retrospectively collected 178 patients (60% for training and 40% for testing) in 2 centers and 61 patients corresponding to 2 further external testing cohorts with LACC between 2010 to 2022 and who had undergone pretreatment analog or digital 18F-FDG PET/CT, pelvic MRI and surgical PALN staging. Only primary tumor volumes were delineated. Radiomics features were extracted using the Radiomics toolbox®. The ComBat harmonization method was applied to reduce the batch effect between centers. Different prediction models were trained using a neural network approach with either clinical, radiomics or combined models. They were then evaluated on the testing and external validation sets and compared. RESULTS: In the training set (n = 102), the clinical model achieved a good prediction of the risk of PALN involvement with a C-statistic of 0.80 (95% CI 0.71, 0.87). However, it performed in the testing (n = 76) and external testing sets (n = 30 and n = 31) with C-statistics of only 0.57 to 0.67 (95% CI 0.36, 0.83). The ComBat-radiomic (GLDZM_HISDE_PET_FBN64 and Shape_maxDiameter2D3_PET_FBW0.25) and ComBat-combined (FIGO 2018 and same radiomics features) models achieved very high predictive ability in the training set and both models kept the same performance in the testing sets, with C-statistics from 0.88 to 0.96 (95% CI 0.76, 1.00) and 0.85 to 0.92 (95% CI 0.75, 0.99), respectively. CONCLUSIONS: Radiomic features extracted from pre-CRT analog and digital 18F-FDG PET/CT outperform clinical parameters in the decision to perform a para-aortic node staging or an extended field irradiation to PALN. Prospective validation of our models should now be carried out.
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Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias do Colo do Útero , Feminino , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/patologia , Estudos Retrospectivos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Imageamento por Ressonância MagnéticaRESUMO
PURPOSE: In this work, we addressed fully automatic determination of tumor functional uptake from positron emission tomography (PET) images without relying on other image modalities or additional prior constraints, in the context of multicenter images with heterogeneous characteristics. METHODS: In cervical cancer, an additional challenge is the location of the tumor uptake near or even stuck to the bladder. PET datasets of 232 patients from five institutions were exploited. To avoid unreliable manual delineations, the ground truth was generated with a semi-automated approach: a volume containing the tumor and excluding the bladder was first manually determined, then a well-validated, semi-automated approach relying on the Fuzzy locally Adaptive Bayesian (FLAB) algorithm was applied to generate the ground truth. Our model built on the U-Net architecture incorporates residual blocks with concurrent spatial squeeze and excitation modules, as well as learnable non-linear downsampling and upsampling blocks. Experiments relied on cross-validation (four institutions for training and validation, and the fifth for testing). RESULTS: The model achieved good Dice similarity coefficient (DSC) with little variability across institutions (0.80 ± 0.03), with higher recall (0.90 ± 0.05) than precision (0.75 ± 0.05) and improved results over the standard U-Net (DSC 0.77 ± 0.05, recall 0.87 ± 0.02, precision 0.74 ± 0.08). Both vastly outperformed a fixed threshold at 40% of SUVmax (DSC 0.33 ± 0.15, recall 0.52 ± 0.17, precision 0.30 ± 0.16). In all cases, the model could determine the tumor uptake without including the bladder. Neither shape priors nor anatomical information was required to achieve efficient training. CONCLUSION: The proposed method could facilitate the deployment of a fully automated radiomics pipeline in such a challenging multicenter context.
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Processamento de Imagem Assistida por Computador , Redes Neurais de Computação , Algoritmos , Teorema de Bayes , Humanos , Tomografia por Emissão de PósitronsRESUMO
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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Háfnio/uso terapêutico , Nanopartículas/uso terapêutico , Óxidos/uso terapêutico , Radiossensibilizantes/uso terapêutico , Sarcoma/terapia , Neoplasias de Tecidos Moles/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radioterapia/métodos , Adulto JovemRESUMO
PURPOSE: The aim of this study was to validate previously developed radiomics models relying on just two radiomics features from 18F-fluorodeoxyglucose positron emission tomography (PET) and magnetic resonance imaging (MRI) images for prediction of disease free survival (DFS) and locoregional control (LRC) in locally advanced cervical cancer (LACC). METHODS: Patients with LACC receiving chemoradiotherapy were enrolled in two French and one Canadian center. Pre-treatment imaging was performed for each patient. Multicentric harmonization of the two radiomics features was performed with the ComBat method. The models for DFS (using the feature from apparent diffusion coefficient (ADC) MRI) and LRC (adding one PET feature to the DFS model) were tuned using one of the French cohorts (n = 112) and applied to the other French (n = 50) and the Canadian (n = 28) external validation cohorts. RESULTS: The DFS model reached an accuracy of 90% (95% CI [79-98%]) (sensitivity 92-93%, specificity 87-89%) in both the French and the Canadian cohorts. The LRC model reached an accuracy of 98% (95% CI [90-99%]) (sensitivity 86%, specificity 100%) in the French cohort and 96% (95% CI [80-99%]) (sensitivity 83%, specificity 100%) in the Canadian cohort. Accuracy was significantly lower without ComBat harmonization (82-85% and 71-86% for DFS and LRC, respectively). The best prediction using standard clinical variables was 56-60% only. CONCLUSIONS: The previously developed PET/MRI radiomics predictive models were successfully validated in two independent external cohorts. A proposed flowchart for improved management of patients based on these models should now be confirmed in future larger prospective studies.
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Quimiorradioterapia , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Viés , Intervalo Livre de Doença , Feminino , Fluordesoxiglucose F18 , Humanos , Pessoa de Meia-Idade , Recidiva , Resultado do Tratamento , Neoplasias do Colo do Útero/patologiaRESUMO
PURPOSE: In inflammatory breast cancer, radiation therapy intensification is considered a standard of care by some teams, although the level of evidence remains low. We sought to analyze the impact of radiation therapy modalities on the risk of loco-regional and distant relapse. METHODS AND MATERIALS: This retrospective multicenter study included patients with localized inflammatory breast cancer treated between 2010 and 2017. Standard postmastectomy radiation therapy consisted of daily fractions to a total dose of 50 Gy equivalent without a boost or bolus, while intensified radiation therapy referred to the use of a boost or bolus. The cumulative incidence curves of locoregional and distant recurrence were displayed using the competing risk method. RESULTS: Of the 241 included patients, 165 were treated with standard and 76 with intensified radiation therapy. There was significantly more nodal involvement in the intensified group. With a median follow-up of 40 months postradiation therapy, there was no difference between standard versus intensified radiation therapy regarding the cumulative incidence of locoregional (P = .68) or distant recurrence (P = .29). At 5 years, the risks of locoregional and distant recurrence were 12.1% (95% CI, 7.5; 17.7) and 29.4% (95% CI, 21.8; 37.3) for patients treated with standard radiation therapy and 10.4% (95% CI, 4.4; 19.3) and 21.4% (95% CI, 12.6; 31.9) for those treated with intensified radiation therapy. In multivariate analyses, triple-negative subtype and absence of complete pathologic response were associated with a higher risk of loco-regional recurrence. Radiation therapy intensification had no significant impact on locoregional and distant recurrence. For patients with a non-complete pathologic response (n = 172, 71.7%), no significant differences were observed between the 2 groups for loco-regional (P = .80) and distant (P = .39) recurrence. Severe toxicity rates were similar in both groups. CONCLUSIONS: Contrary to other important series, this large retrospective multicentric study did not show a locoregional or distant control benefit of intensified radiation therapy. Pooled prospective studies and meta-analyses of intensified radiation therapy are warranted to endorse this approach.
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The sentinel lymph node technique is minimally invasive and used routinely by surgeons, reducing the need for morbid extensive lymph node dissections, which is a significant advantage for cancer staging and treatment decisions. The sentinel lymph node could also help radiation oncologists to identify tumor drainage for each of their patients, leading to a more personalized radiotherapy, instead of a probabilistic irradiation based on delineation atlases. The aim is both to avoid recurrence in unexpected areas and to limit the volume of irradiated healthy tissues. The aim of our study is to evaluate the impact of sentinel lymph node mapping for radiation oncologists. This concept, relying on sentinel lymph node mapping for treatment planning, is known as lymph-flow-guided radiotherapy. We present an up-to-date narrative literature review showing the potential applications of the sentinel lymph node technique for radiotherapy, as well as the limits that need to be addressed before its routine usage.
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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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Lipossarcoma , Segunda Neoplasia Primária , Radioterapia de Intensidade Modulada , Humanos , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Segunda Neoplasia Primária/etiologia , Recidiva Local de Neoplasia/patologia , Lipossarcoma/radioterapia , Lipossarcoma/cirurgia , Lipossarcoma/etiologiaRESUMO
PURPOSE: Act.In.Sarc (NCT02379845) demonstrated that the first-in-class radioenhancer NBTXR3, activated by preoperative radiation therapy (RT), doubled the rate of pathologic complete response after resection compared with preoperative RT alone in adult patients with locally advanced soft tissue sarcoma of the extremity or trunk wall (16.1% vs 7.9%, P = .045), and more patients achieved R0 resections (77.0% vs 64.0%, P = .042). These are the toxicity and health-related quality of life (HRQoL) results. METHODS AND MATERIALS: Act.In.Sarc randomized eligible patients 1:1 to either NBTXR3 (single intratumoral injection, volume equivalent to 10% of baseline tumor volume, at 53.3 g/L) activated by external-beam RT (arm A) or external-beam RT alone (arm B) (50 Gy in 25 fractions), followed by surgery in both arms. Here, we report the safety analyses in the all-treated population with a long-term follow-up of at least 2 years, and HRQoL in the intention-to-treat full analysis set. RESULTS: During the on-treatment period, serious adverse events (SAEs) of all grades related to NBTXR3 occurred in 10.1% (9/89) of patients (arm A), and SAEs related to RT occurred in 5.6% (5/89) (arm A) versus 5.6% (5/90) (arm B); postsurgery hospitalization owing to SAEs occurred in 15.7% (14/89) (arm A) versus 24.4% (22/90) (arm B). During the follow-up period, posttreatment SAEs (regardless of relationship) occurred in 13.5% (12/89) (arm A) versus 24.4% (22/90) (arm B). NBTXR3 did not negatively affect HRQoL; during the follow-up period, there was an improvement in most mean Toronto extremity salvage, EuroQoL 5-dimension (EQ-5D), EQ5D02-EQ visual analog scale, reintegration to normal living index, and musculoskeletal tumor rating scale scores. CONCLUSIONS: NBTXR3 did not negatively affect safety or HRQoL. Long-term safety results reinforce the favorable benefit-risk ratio of NBTXR3 plus RT.
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Antineoplásicos , Sarcoma , Neoplasias de Tecidos Moles , Adulto , Antineoplásicos/uso terapêutico , Humanos , Terapia Neoadjuvante , Qualidade de Vida , Compostos Radiofarmacêuticos/uso terapêutico , Sarcoma/tratamento farmacológico , Sarcoma/radioterapia , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/radioterapia , Neoplasias de Tecidos Moles/cirurgiaRESUMO
PURPOSE: To facilitate the demonstration of the prognostic value of radiomics, multicenter radiomics studies are needed. Pooling radiomic features of such data in a statistical analysis is however challenging, as they are sensitive to the variability in scanner models, acquisition protocols and reconstruction settings, which is often unavoidable in a multicentre retrospective analysis. A statistical harmonization strategy called ComBat was utilized in radiomics studies to deal with the "center-effect". The goal of the present work was to integrate a transfer learning (TL) technique within ComBat-and recently developed alternate versions of ComBat with improved flexibility (M-ComBat) and robustness (B-ComBat)-to allow the use of a previously determined harmonization transform to the radiomic feature values of new patients from an already known center. MATERIAL AND METHODS: The proposed TL approach were incorporated in the four versions of ComBat (standard, B, M, and B-M ComBat). The proposed approach was evaluated using a dataset of 189 locally advanced cervical cancer patients from 3 centers, with magnetic resonance imaging (MRI) and positron emission tomography (PET) images, with the clinical endpoint of predicting local failure. The impact performance of the TL approach was evaluated by comparing the harmonization achieved using only parts of the data to the reference (harmonization achieved using all the available data). It was performed through three different machine learning pipelines. RESULTS: The proposed TL technique was successful in harmonizing features of new patients from a known center in all versions of ComBat, leading to predictive models reaching similar performance as the ones developed using the features harmonized with all the data available. CONCLUSION: The proposed TL approach enables applying a previously determined ComBat transform to new, previously unseen data.
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Colo do Útero/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/normas , Aprendizado de Máquina/normas , Neoplasias do Colo do Útero/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Colo do Útero/patologia , Quimiorradioterapia/métodos , Conjuntos de Dados como Assunto , Sistemas de Apoio a Decisões Clínicas/normas , Sistemas de Apoio a Decisões Clínicas/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Interpretação de Imagem Assistida por Computador/estatística & dados numéricos , Aprendizado de Máquina/estatística & dados numéricos , Imageamento por Ressonância Magnética/normas , Imageamento por Ressonância Magnética/estatística & dados numéricos , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/normas , Tomografia por Emissão de Pósitrons/estatística & dados numéricos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/normas , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Resultado do Tratamento , Neoplasias do Colo do Útero/terapia , Adulto JovemRESUMO
Glioblastoma (GBM) is frequent in elderly patients, but their frailty provokes debate regarding optimal treatment in general, and the standard 6-week chemoradiation (CRT) in particular, although this is the mainstay for younger patients. All patients with newly diagnosed GBM and age ≥ 70 who were referred to our institution for 6-week CRT were reviewed from 2004 to 2018. MGMT status was not available for treatment decision at that time. The primary endpoint was overall survival (OS). Secondary outcomes were progression-free survival (PFS), early adverse neurological events without neurological progression ≤ 1 month after CRT and temozolomide hematologic toxicity assessed by CTCAE v5. 128 patients were included. The median age was 74.1 (IQR: 72-77). 15% of patients were ≥ 80 years. 62.5% and 37.5% of patients fulfilled the criteria for RPA class I-II and III-IV, respectively. 81% of patients received the entire CRT and 28% completed the maintenance temozolomide. With median follow-up of 11.7 months (IQR: 6.5-17.5), median OS was 11.7 months (CI 95%: 10-13 months). Median PFS was 9.5 months (CI 95%: 9-10.5 months). 8% of patients experienced grade ≥ 3 hematologic events. 52.5% of patients without neurological progression had early adverse neurological events. Post-operative neurological disabilities and age ≥ 80 were not associated with worsened outcomes. 6-week chemoradiation was feasible for "real-life" elderly patients diagnosed with glioblastoma, even in the case of post-operative neurological disabilities. Old does not necessarily mean worse.
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Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Fatores Etários , Idoso , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/diagnóstico , Quimiorradioterapia , Feminino , Seguimentos , Glioblastoma/diagnóstico , Humanos , Masculino , Análise de Sobrevida , Temozolomida/efeitos adversos , Temozolomida/uso terapêuticoRESUMO
PURPOSES: Firstly, to evaluate the impact of completion hysterectomy after chemoradiation and image-guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer. Secondly, to assess a potential differential dose-effect relationship for the rectum and bladder according to the realization of hysterectomy. MATERIAL AND METHODS: Two cohorts of patients were identified, differing by the realization of completion hysterectomy. Inclusions were limited to FIGO stage I-II, with no para-aortic involvement. All patients received a combination of pelvic chemoradiation followed by IGABT. Their outcomes and morbidity were reviewed. Log-rank tests were used to compare survivals. Probit analyses were performed to study dose-volume effect relationships. RESULTS: The two cohorts comprised 54 patients in the completion surgery group and 157 patients in the definitive radiotherapy group. They were well balanced, except for the mean follow-up, significantly longer in the post hysterectomy cohort and the use of PET-CT in the work-up, more frequent in the definitive radiotherapy cohort. Although less local relapses were reported in the hysterectomy group, the 5-year disease-free and overall survival did not differ between groups. The cumulative incidence of severe late morbidity was significantly increased in the hysterectomy cohort: 22.5% versus 6.5% at 5years (p=0.016). Dose-volume effects were observed for the bladder, with the D2cm3 corresponding with a 10% probability of late severe morbidity urinary events (ED10) of 67.8Gy and 91.9Gy in the hysterectomy and definitive radiotherapy cohorts, respectively. A D90 CTVHR of 85Gy (planning aim) corresponded with a 93.3% rate of local control in the definitive radiotherapy cohort whereas it corresponded with a 77.3% chance to have a good histologic response (complete response or microscopic residual disease) in the hysterectomy group. CONCLUSION: No benefit from completion hysterectomy in terms of overall or disease-free survival rates was observed, which was moreover responsible for an increase of the severe late morbidity. The realization of post-radiation hysterectomy resulted in a shift of the ED10 of 24.1Gy.
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Radioterapia Guiada por Imagem/métodos , Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Braquiterapia/efeitos adversos , Braquiterapia/métodos , Quimiorradioterapia , Terapia Combinada , Intervalo Livre de Doença , Relação Dose-Resposta à Radiação , Feminino , Humanos , Histerectomia/efeitos adversos , Histerectomia/métodos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Estadiamento de Neoplasias , Neoplasia Residual , Radiometria/métodos , Radioterapia Conformacional/métodos , Radioterapia Guiada por Imagem/efeitos adversos , Reto/efeitos da radiação , Resultado do Tratamento , Bexiga Urinária/efeitos da radiação , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/patologiaRESUMO
INTRODUCTION: Hypofractionated stereotactic radiation therapy (HSRT) for vertebral metastases gives good results in terms of local control but increases the risk of fracture in the treated volume. Preclinical and clinical studies have shown that zoledronate not only reduces the risk of fracture and stimulates osteoclastic remodeling but also increases the immune response and radiosensitivity. This study aimed to evaluate the tolerability and effectiveness of zoledronate in association with radiation therapy. PATIENTS AND METHODS: We conducted a multicenter phase 1 study that combined HSRT (3 × 9 Gy) and zoledronate in patients with vertebral metastasis (NCT01219790). The principal objective was the absence of spinal cord adverse reactions at 1 year. The secondary objectives were acute tolerability, the presentation of a bone event, local tumor control, pain control, progression-free survival, and overall survival. RESULTS: Thirty patients (25 male, 5 female), median age 66 years, who were followed up for a median period of 19.2 months, received treatment for 49 vertebral metastases. A grade 3 acute mucosal adverse event occurred in 1 patient during the treatment and in 2 more at 1 month. No late neurologic adverse events were reported at 1 year. The mean pain scores diminished significantly at 1 month (1.35; P=.0125) and 3 months (0.77; P<.0001) compared with pain scores at study entry (2.49). Vertebral collapse in the irradiated zone occurred in 1 (2%) treated vertebra. Control of local disease was achieved in 94% of irradiated patients (3 local recurrences). CONCLUSION: The combination of zoledronate and HSRT in the treatment of vertebral metastasis is well tolerated and seems to reduce the rate of vertebral collapse, effectively relieve pain, and achieve good local tumor control with no late neurologic adverse effects.
Assuntos
Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Imidazóis/efeitos adversos , Hipofracionamento da Dose de Radiação , Radiocirurgia/métodos , Neoplasias da Coluna Vertebral/radioterapia , Neoplasias da Coluna Vertebral/secundário , Idoso , Conservadores da Densidade Óssea/administração & dosagem , Terapia Combinada , Difosfonatos/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Imidazóis/administração & dosagem , Estimativa de Kaplan-Meier , Masculino , Medição da Dor , Medula Espinal/efeitos da radiação , Neoplasias da Coluna Vertebral/mortalidade , Ácido ZoledrônicoRESUMO
PURPOSE: To identify the prognostic role of adjuvant abdominal radiation therapy (RT) on oncologic outcomes as a part of multimodal treatment in the management of desmoplastic small round cell tumor (DSRCT) and to determine its impact according to the quality of surgical resection. METHODS AND MATERIALS: All patients treated for primary abdominal DSRCT in 8 French centers from 1991 to 2014 were included. Patients were retrospectively staged into 3 groups: group A treated with adjuvant RT after cytoreductive surgery, group B without RT after cytoreductive surgery, and group C by exclusive chemotherapy. Peritoneal progression-free survival (PPFS), progression-free survival (PFS), and overall survival (OS) were evaluated. We also performed a direct comparison between groups A and B to evaluate RT after cytoreductive surgery. Radiation therapy was also evaluated according to completeness of surgery: complete cytoreductive surgery (CCS) or incomplete cytoreductive surgery (ICS). RESULTS: Thirty-seven (35.9%), thirty-six (34.9%), and thirty (28.0%) patients were included in groups A, B, and C, respectively. Three-year OS was 61.2% (range, 41.0%-76.0%), 37.6% (22.0%-53.1%), and 17.3% (6.3%-32.8%) for groups A, B, and C, respectively. Overall survival, PPFS, and PFS differed significantly among the 3 groups (P<.001, P<.001, and P<.001, respectively). Overall survival and PPFS were higher in group A (RT group) compared with group B (no RT group) (P=.045 and P=.006, respectively). Three-year PPFS was 23.8% (10.3%-40.4%) for group A and 12.51% (4.0%-26.2%) for group B. After CCS, RT improved PPFS (P=.024), but differences in OS and PFS were not significant (P=.40 and P=.30, respectively). After ICS, RT improved OS (P=.044). A trend of PPFS and PFS increase was observed, but the difference was not statistically significant (P=.073 and P=.076). CONCLUSIONS: Adjuvant RT as part of multimodal treatment seems to confer oncologic benefits for patients treated for abdominal DSRCT after cytoreductive surgery and perioperative chemotherapy.
Assuntos
Neoplasias Abdominais/radioterapia , Tumor Desmoplásico de Pequenas Células Redondas/radioterapia , Neoplasias Abdominais/mortalidade , Neoplasias Abdominais/cirurgia , Adolescente , Adulto , Criança , Pré-Escolar , Terapia Combinada , Tumor Desmoplásico de Pequenas Células Redondas/mortalidade , Tumor Desmoplásico de Pequenas Células Redondas/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radioterapia Adjuvante , Estudos RetrospectivosRESUMO
BACKGROUND: Infiltrating squamous cell carcinoma (SCC) of the lower lip is a highly curable cancer. We retrospectively analyzed oncologic, functional, and cosmetic outcomes after interstitial low-dose rate brachytherapy at 58 Gy (50-62) of lower lip SCC treated in our institution. METHODS: There were 89 patients (44 T1, 33 T2, 2 T3, and 10 after wedge-excision). All tumors were N0 at the time of treatment. We calculated survival rates and assessed functional and cosmetic results de visu. RESULTS: After a median follow-up of 36 months (range, 9-127), 5-year local control rate was 95% and 5-year disease-free survival was 82%. Only 6 patients (5 T2 and 1 T3) developed secondary cervical nodal involvement. Sixty-one patients were reassessed and 11 patients presented mild functional troubles. Cosmetic results were good (77%) or fair (21%). CONCLUSION: Brachytherapy provided a high local disease control rate, excellent functional results, and good cosmetic outcomes for SCCs of the lip. Risk of cervical node involvement was low with small tumors.