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1.
Strahlenther Onkol ; 199(10): 901-909, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37256301

RESUMEN

BACKGROUND: Our study aims to identify predictive factors of moderate to severe (grade ≥ 2) late toxicity after reirradiation (reRT) of recurrent head and neck carcinoma (HNC) and explore the correlations between dose organs at risk (OAR) and grade ≥ 2 toxicity. MATERIAL AND METHODS: Between 09/2007 and 09/2019, 55 patients were re-irradiated with IMRT or proton therapy with curative intent for advanced HNC. Our study included all patients for whom data from the first and second irradiations were available. Co-variables, including interval to reRT, size of re-irradiated PTV, and dose to OAR, were analyzed as potential predictors for developing moderate to severe long-term toxicity with death as a competing risk. Receiver-operator characteristics (ROC) analysis assessed the association between dose/volume parameters and the risk of toxicity. RESULTS: Twenty-three patients participated in our study. After a median follow-up of 41 months, 65% of the patients experienced grade ≥ 2 late toxicity. The average dose to pharyngeal constrictor muscles (PCM) at the time of reRT showed an association with the risk of grade ≥ 2 dysphagia: AUC = 0.78 (95% CI: 0.53-1), optimal cut-off value = 36.7 Gy (sensitivity 62%/specificity 100%). The average dose to the oral cavity at the time of reRT showed an association with the risk of grade ≥ 2 dysgeusia: AUC = 0.96 (0.89-1), optimal cut-off value = 20.5 Gy (sensitivity 100%/specificity 88%). CONCLUSION: Our analysis depicted an association between the dose to OAR and the risk of developing moderate to severe dysphagia and dysgeusia and proposed new dose constraints for PCM (36.7 Gy) and oral cavity (20.5 Gy).


Asunto(s)
Carcinoma , Trastornos de Deglución , Neoplasias de Cabeza y Cuello , Terapia de Protones , Radioterapia de Intensidad Modulada , Reirradiación , Humanos , Radioterapia de Intensidad Modulada/efectos adversos , Reirradiación/efectos adversos , Terapia de Protones/efectos adversos , Disgeusia , Trastornos de Deglución/etiología , Neoplasias de Cabeza y Cuello/radioterapia , Carcinoma/radioterapia , Boca , Músculos , Dosificación Radioterapéutica , Recurrencia Local de Neoplasia/radioterapia
2.
Eur J Nucl Med Mol Imaging ; 50(2): 559-571, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36282298

RESUMEN

PURPOSE: To evaluate whether radiomics from [18F]-FDG PET and/or MRI before re-irradiation (reRT) of recurrent head and neck cancer (HNC) could predict the occurrence and the location "in-field" or "outside" of a second locoregional recurrence (LR). METHODS: Among the 55 patients re-irradiated at curative intend for HNC from 2012 to 2019, 48 had an MRI and/or PET before the start of the reRT. Thirty-nine radiomic features (RF) were extracted from the re-irradiated GTV (rGTV) using LIFEx software. Student t tests and Spearman correlation coefficient were used to select the RF that best separate patients who recurred from those who did not, and "in-field" from "outside" recurrences. Principal component analysis involving these features only was used to create a prediction model. Leave-one-out cross-validation was performed to evaluate the models. RESULTS: After a median follow-up of 17 months, 40/55 patients had developed a second LR, including 18 "in-field" and 22 "outside" recurrences. From pre-reRT MRI, a model based on three RF (GLSZM_SZHGLE, GLSZM_LGLZE, and skewness) predicted whether patients would recur with a balanced accuracy (BA) of 83.5%. Another model from pre-reRT MRI based on three other RF (GLSZM_ LZHGE, NGLDM_Busyness, and GLZLM_SZE) predicted whether patients would recur "in-field" or "outside" with a BA of 78.5%. From pre-reRT PET, a model based on four RF (Kurtosis, SUVbwmin, GLCM_Correlation, and GLCM_Contrast) predicted the LR location with a BA of 84.5%. CONCLUSION: RF characterizing tumor heterogeneity extracted from pre-reRT PET and MRI predicted whether patients would recur, and whether they would recur "in-field" or "outside".


Asunto(s)
Neoplasias de Cabeza y Cuello , Reirradiación , Humanos , Fluorodesoxiglucosa F18 , Recurrencia Local de Neoplasia/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/radioterapia , Imagen por Resonancia Magnética
3.
Eur J Nucl Med Mol Imaging ; 50(13): 4024-4035, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37606858

RESUMEN

PURPOSE: To determine if pretreatment [18F]FDG PET/CT could contribute to predicting complete pathological complete response (pCR) in patients with early-stage triple-negative breast cancer (TNBC) undergoing neoadjuvant chemotherapy with or without pembrolizumab. METHODS: In this retrospective bicentric study, we included TNBC patients who underwent [18F]FDG PET/CT before neoadjuvant chemotherapy (NAC) or chemo-immunotherapy (NACI) between March 2017 and August 2022. Clinical, biological, and pathological data were collected. Tumor SUVmax and total metabolic tumor volume (TMTV) were measured from the PET images. Cut-off values were determined using ROC curves and a multivariable model was developed using logistic regression to predict pCR. RESULTS: N = 191 patients were included. pCR rates were 53 and 70% in patients treated with NAC (N = 91) and NACI (N = 100), respectively (p < 0.01). In univariable analysis, high Ki67, high tumor SUVmax (> 12.3), and low TMTV (≤ 3.0 cm3) were predictors of pCR in the NAC cohort while tumor staging classification (< T3), BRCA1/2 germline mutation, high tumor SUVmax (> 17.2), and low TMTV (≤ 7.3 cm3) correlated with pCR in the NACI cohort. In multivariable analysis, only high tumor SUVmax (NAC: OR 8.8, p < 0.01; NACI: OR 3.7, p = 0.02) and low TMTV (NAC: OR 6.6, p < 0.01; NACI: OR 3.5, p = 0.03) were independent factors for pCR in both cohorts, albeit at different thresholds. CONCLUSION: High tumor metabolism (SUVmax) and low tumor burden (TMTV) could predict pCR after NAC regardless of the addition of pembrolizumab. Further studies are warranted to validate such findings and determine how these biomarkers could be used to guide neoadjuvant therapy in TNBC patients.


Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Neoplasias de la Mama Triple Negativas/diagnóstico por imagen , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Fluorodesoxiglucosa F18 , Terapia Neoadyuvante/métodos , Proteína BRCA1 , Radiofármacos/uso terapéutico , Estudios Retrospectivos , Proteína BRCA2
4.
Eur J Nucl Med Mol Imaging ; 48(11): 3560-3570, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33774685

RESUMEN

PURPOSE: We evaluated whether biomarkers on baseline [18F]-FDG PET/CT are associated with recurrence after surgery in patients with invasive breast cancer of no special type (NST). METHODS: In this retrospective single-center study, we included consecutive patients with non-metastatic breast cancer of NST who underwent [18F]-FDG PET/CT before treatment, including surgery, between 2011 and 2016. Clinicopathological data were collected. Tumor SUVmax, total metabolic tumor volume (TMTV), and spleen- and bone marrow-to-liver SUVmax ratios (SLR, BLR) were measured from the PET images. Cut-off values were determined using predictiveness curves to predict 5-year recurrence-free survival (5y-RFS). A multivariable prediction model was developed using Cox regression. The association with stromal tumor-infiltrating lymphocytes (TILs) levels (low if <50%) was studied by logistic regression. RESULTS: Three hundred and three women were eligible, including 93 (31%) with triple-negative breast carcinoma. After a median follow-up of 6.2 years, 56 and 35 patients experienced recurrence and death, respectively. The 5y-RFS rate was 86%. In multivariable analyses, high TMTV (>20 cm3) and high SLR (>0.76) were associated with shorter 5y-RFS (HR 2.4, 95%CI 1.3-4.5, and HR 1.9, 95%CI 1.0-3.6). In logistic regression, high SLR was the only independent factor associated with low stromal TILs (OR 2.8, 95%CI 1.4-5.7). CONCLUSION: High total metabolic tumor volume and high spleen glucose metabolism on baseline [18F]-FDG PET/CT were associated with poor 5y-RFS after surgical resection in patients with breast cancer of NST. Spleen metabolism was inversely correlated with stromal TILs and might be a surrogate for an immunosuppressive tumor microenvironment.


Asunto(s)
Neoplasias de la Mama , Fluorodesoxiglucosa F18 , Biomarcadores , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Femenino , Humanos , Recurrencia Local de Neoplasia/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Pronóstico , Estudios Retrospectivos , Bazo/diagnóstico por imagen , Carga Tumoral , Microambiente Tumoral
7.
Cancer Treat Rev ; 124: 102684, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38278078

RESUMEN

BACKGROUND: Radiation therapy (RT) is essential in treating advanced lung cancer, but may lead to radiation pneumonitis (RP). This systematic review investigates the use of pulmonary function tests (PFT) and other parameters to predict and mitigate RP, thereby improving RT planning. METHODS: A systematic review sifted through PubMed and on BioMed Central, targeting articles from September 2005 to December 2022 containing the keywords: Lung Cancer, Radiotherapy, and pulmonary function test. RESULTS: From 1153 articles, 80 were included. RP was assessed using CTCAEv.4 in 30 % of these. Six studies evaluated post-RT quality of life in lung cancer patients, reporting no decline. Patients with RP and chronic obstructive pulmonary disease (COPD) generally exhibited poorer overall survival. Notably, forced expiratory volume in one second (FEV1) and diffusing capacity of the lung for carbon monoxide (DLCO) declined 24 months post-RT, while forced vital capacity (FVC) stayed stable. In the majority of studies, age over 60, tumors located in the lower part of the lung, and low FEV1 before RT were associated with a higher risk of RP. Dosimetric factors (V5, V20, MLD) and metabolic imaging emerged as significant predictors of RP risk. A clinical checklist blending patient and tumor characteristics, PFT results, and dosimetric criteria was proposed for assessing RP risk before RT. CONCLUSION: The review reveals the multifactorial nature of RP development following RT in lung cancer. This approach should guide individualized management and calls for a prospective study to validate these findings and enhance RP prevention strategies.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Neumonitis por Radiación , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Pulmón/patología , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patología , Estudios Prospectivos , Calidad de Vida , Neumonitis por Radiación/etiología , Neumonitis por Radiación/prevención & control , Neumonitis por Radiación/patología , Medición de Riesgo
8.
Int J Radiat Biol ; 100(1): 79-86, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37526368

RESUMEN

BACKGROUND: To investigate the outcomes of patients who underwent curative reirradiation (reRT), with intensity-modulated radiation therapy (IMRT) or proton therapy (PT) for unresectable recurrent or second primary head and neck adenoid cystic carcinoma (HNACC). METHODS: Ten patients, mostly KPS 90%, were reirradiated (3/10 with IMRT and 7/10 with PT) at a median maximum dose to the CTV of 64.2 Gy from July 2011 to November 2021. Locations at the time of reRT were mainly the sinus (4/10) and the salivary glands (including the parotid and submandibular gland, 3/10). CTCAEv5 was used to assess acute and late toxicities. Follow-up was the time between the end of reRT and the date of last news. RESULTS: The median time between the two irradiations was 53.5 months (IQR: 18-84). After a median follow-up of 26 months (range, 12.5-51.8 months), six patients had developed a locoregional recurrence (LR), of which four occurred within the previously irradiated volume. Two and three-year locoregional failure-free survival (LFFS) and overall survival (OS) were 55.6% [95%CI: 31-99.7%], and 41% [18.5-94%] and 66.7% [42-100%] and 44.4% [21.4-92.3%], respectively. LFFS and OS were significantly better in the subgroup of sinus tumors (p = .013) and the subgroup of patients re-irradiated more than two years after the first course of irradiation (p = .01). Seven patients had impairments before the start of reRT, including hearing impairment (3/10) and facial nerve impairment (3/10). The most severe late toxicities were brain necrosis (2/10), osteoradionecrosis (1/10) and vision decreased (1/10). CONCLUSION: Curative reRT for HNACC is possible for selected cases, but the LR rate in the irradiated field and the risk of severe toxicity remain high. Improved selection criteria and more carefully defined target volumes may improve outcome in these patients. A further study including larger cohort of patients would be useful to confirm these results.


Asunto(s)
Carcinoma Adenoide Quístico , Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Reirradiación , Humanos , Carcinoma Adenoide Quístico/radioterapia , Carcinoma Adenoide Quístico/etiología , Reirradiación/efectos adversos , Reirradiación/métodos , Carcinoma de Células Escamosas/radioterapia , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/etiología , Neoplasias de Cabeza y Cuello/radioterapia
9.
Eur J Nucl Med Mol Imaging ; 40(8): 1206-13, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23640467

RESUMEN

PURPOSE: Inflammatory breast cancer (IBC) is the most aggressive type of breast cancer with a poor prognosis. Locoregional staging is based on dynamic contrast-enhanced (DCE) CT or MRI. The aim of this study was to compare the performances of FDG PET/CT and DCE CT in locoregional staging of IBC and to assess their respective prognostic values. METHODS: The study group comprised 50 women (median age: 51 ± 11 years) followed in our institution for IBC who underwent FDG PET/CT and DCE CT scans (median interval 5 ± 9 days). CT enhancement parameters were net maximal enhancement, net early enhancement and perfusion. RESULTS: The PET/CT scans showed intense FDG uptake in all primary tumours. Concordance rate between PET/CT and DCE CT for breast tumour localization was 92%. No significant correlation was found between SUVmax and CT enhancement parameters in primary tumours (p > 0.6). PET/CT and DCE CT results were poorly correlated for skin infiltration (kappa = 0.19). Ipsilateral foci of increased axillary FDG uptake were found in 47 patients (median SUV: 7.9 ± 5.4), whereas enlarged axillary lymph nodes were observed on DCE CT in 43 patients. Results for axillary node involvement were fairly well correlated (kappa = 0.55). Nineteen patients (38%) were found to be metastatic on PET/CT scan with a significant shorter progression-free survival than patients without distant lesions (p = 0.01). In the primary tumour, no statistically significant difference was observed between high and moderate tumour FDG uptake on survival, using an SUVmax cut-off of 5 (p = 0.7 and 0.9), or between high and low tumour enhancement on DCE CT (p > 0.8). CONCLUSION: FDG PET/CT imaging provided additional information concerning locoregional involvement to that provided by DCE CT on and allowed detection of distant metastases in the same whole-body procedure. Tumour FDG uptake or CT enhancement parameters were not correlated and were not found to have any prognostic value.


Asunto(s)
Carcinoma/diagnóstico , Neoplasias Inflamatorias de la Mama/diagnóstico , Imagen Multimodal , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Adulto , Femenino , Fluorodesoxiglucosa F18 , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Pronóstico , Radiofármacos
10.
Clin Nucl Med ; 48(5): e228-e229, 2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-36854307

RESUMEN

ABSTRACT: A 73-year-old woman was referred for 68 Ga-DOTATOC PET/CT staging of a grade 2 pancreatic neuroendocrine tumor, which showed the primary pancreatic tumor, liver metastases, one left pleural metastasis, and high uptake in a mass of the right triceps brachii muscle. Two years before, she underwent 18 F-FDG PET/CT and 111 In-pentetreotide scan, respectively, with low and high uptake of each radiotracer in the triceps mass. Histopathological analysis revealed a solitary fibrous tumor. Immunohistochemistry showed no staining for SSTR-2 and SSTR-5, suggesting tumor overexpression of another somatostatin receptor. This case highlighted a potential pitfall on 68 Ga-DOTATOC PET/CT.


Asunto(s)
Hemangiopericitoma , Tumores Neuroendocrinos , Compuestos Organometálicos , Neoplasias Pancreáticas , Tumores Fibrosos Solitarios , Femenino , Humanos , Anciano , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Octreótido , Tomografía de Emisión de Positrones/métodos , Neoplasias Pancreáticas/patología , Receptores de Somatostatina , Tumores Neuroendocrinos/diagnóstico por imagen , Tumores Neuroendocrinos/patología
11.
J Clin Med ; 12(17)2023 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-37685551

RESUMEN

BACKGROUND: [18F]FDG PET/CT is used for staging and could also provide information associated with clinical outcomes. The objective of this study was to determine the clinical utility of biomarkers measured using [18F]FDG PET/CT to predict the absence of pathological complete response (no-pCR) and recurrence. METHODS: In this retrospective study, we included patients with non-special-type breast carcinoma who underwent [18F]FDG PET/CT before neoadjuvant chemotherapy between 2011 and 2019. Clinicopathological data were collected. Tumor SUVmax and total metabolic tumor volume (TMTV) were measured from PET images. The association between biomarkers and no-pCR was studied using logistic regression. The cut-off value was determined using the area under the ROC Curve. To predict 3-year recurrence-free survival (RFS), we used a multivariable Cox model, and the cut-off value was determined using time-dependent ROC and predictiveness curves. RESULTS: Two hundred and eighty-six patients were included in the analysis. One hundred and twelve patients had a pCR (39.2%). The pCR rate was significantly higher in patients with a high nuclear grade (p < 0.01), HER2+ and TNBC subtypes (p < 0.01), high Ki67 (p < 0.01), and low TMTV (p < 0.01). A high TMTV value (>9.0 cm3) was significantly associated with no-pCR in the whole cohort (OR = 2.4, 95% CI: 1.3-4.2, p < 0.01). After a median follow-up of 4.5 years, 65 patients experienced recurrence and 39 patients died. High TMTV (>13.5 cm3) was associated with shorter RFS (HR = 4.0, 95% CI: 1.9-8.4, p < 0.01). CONCLUSION: High TMTV in pre-therapeutic imaging is associated with no-pCR and recurrence. It can help in identifying high-risk patients and be considered as an intensified or alternative adjuvant therapy for closely monitoring patients.

12.
Cancers (Basel) ; 15(8)2023 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-37190152

RESUMEN

Background: We aimed to evaluate the prognostic value of imaging biomarkers on 18F-FDG PET/CT in extensive-stage small-cell lung cancer (ES-SCLC) patients undergoing first-line chemo-immunotherapy. Methods: In this multicenter and retrospective study, we considered two cohorts, depending on the type of first-line therapy: chemo-immunotherapy (CIT) versus chemotherapy alone (CT). All patients underwent baseline 18-FDG PET/CT before therapy between June 2016 and September 2021. We evaluated clinical, biological, and PET parameters, and used cutoffs from previously published studies or predictiveness curves to assess the association with progression-free survival (PFS) or overall survival (OS) with Cox prediction models. Results: Sixty-eight patients were included (CIT: CT) (36: 32 patients). The median PFS was 5.9:6.5 months, while the median OS was 12.1:9.8 months. dNLR (the derived neutrophils/(leucocytes-neutrophils) ratio) was an independent predictor of short PFS and OS in the two cohorts (p < 0.05). High total metabolic tumor volume (TMTVhigh if > 241 cm3) correlated with outcomes, but only in the CIT cohort (PFS for TMTVhigh in multivariable analysis: HR 2.5; 95%CI 1.1-5.9). Conclusion: Baseline 18F-FDG PET/CT using TMTV could help to predict worse outcomes for ES-SCLC patients undergoing first-line CIT. This suggests that baseline TMTV may be used to identify patients that are unlikely to benefit from CIT.

13.
J Clin Med ; 12(15)2023 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-37568284

RESUMEN

HER2 (Human Epidermal Growth Factor Receptor 2)-positive breast cancer is characterized by amplification of the HER2 gene and is associated with more aggressive tumor growth, increased risk of metastasis, and poorer prognosis when compared to other subtypes of breast cancer. HER2 expression is therefore a critical tumor feature that can be used to diagnose and treat breast cancer. Moving forward, advances in HER2 in vivo imaging, involving the use of techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT), may allow for a greater role for HER2 status in guiding the management of breast cancer patients. This will apply both to patients who are HER2-positive and those who have limited-to-minimal immunohistochemical HER2 expression (HER2-low), with imaging ultimately helping clinicians determine the size and location of tumors. Additionally, PET and SPECT could help evaluate effectiveness of HER2-targeted therapies, such as trastuzumab or pertuzumab for HER2-positive cancers, and specially modified antibody drug conjugates (ADC), such as trastuzumab-deruxtecan, for HER2-low variants. This review will explore the current and future role of HER2 imaging in personalizing the care of patients diagnosed with breast cancer.

14.
Nat Commun ; 14(1): 3698, 2023 06 22.
Artículo en Inglés | MEDLINE | ID: mdl-37349318

RESUMEN

Concurrent chemoradiotherapy (CRT) with blockade of the PD-1 pathway may enhance immune-mediated tumor control through increased phagocytosis, cell death, and antigen presentation. The NiCOL phase 1 trial (NCT03298893) is designed to determine the safety/tolerance profile and the recommended phase-II dose of nivolumab with and following concurrent CRT in 16 women with locally advanced cervical cancer. Secondary endpoints include objective response rate (ORR), progression free survival (PFS), disease free survival, and immune correlates of response. Three patients experience grade 3 dose-limiting toxicities. The pre-specified endpoints are met, and overall response rate is 93.8% [95%CI: 69.8-99.8%] with a 2-year PFS of 75% [95% CI: 56.5-99.5%]. Compared to patients with progressive disease (PD), progression-free (PF) subjects show a brisker stromal immune infiltrate, higher proximity of tumor-infiltrating CD3+ T cells to PD-L1+ tumor cells and of FOXP3+ T cells to proliferating CD11c+ myeloid cells. PF show higher baseline levels of PD-1 and ICOS-L on tumor-infiltrating EMRA CD4+ T cells and tumor-associated macrophages, respectively; PD instead, display enhanced PD-L1 expression on TAMs, higher peripheral frequencies of proliferating Tregs at baseline and higher PD-1 levels at week 6 post-treatment initiation on CD4 and CD8 T cell subsets. Concomitant nivolumab plus definitive CRT is safe and associated with encouraging PFS rates. Further validation in the subset of locally advanced cervical cancer displaying pre-existing, adaptive immune activation is warranted.


Asunto(s)
Neoplasias Pulmonares , Neoplasias del Cuello Uterino , Humanos , Femenino , Nivolumab/uso terapéutico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Antígeno B7-H1 , Receptor de Muerte Celular Programada 1 , Quimioradioterapia , Neoplasias Pulmonares/tratamiento farmacológico
15.
J Neurosurg ; 139(5): 1270-1280, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37029667

RESUMEN

OBJECTIVE: Chordomas are rare bone neoplasms characterized by a high recurrence rate and no benefit from any approved medical treatment to date. However, the investigation of molecular alterations in chordomas could be essential to prognosticate, guide clinical decision-making, and identify theranostic biomarkers. The aim of this study was to provide a detailed genomic landscape of a homogeneous series of 64 chordoma samples, revealing driver events, theranostic markers, and outcome-related genomic features. METHODS: The authors conducted whole-exome sequencing (WES), targeted next-generation sequencing, and RNA sequencing of 64 skull base and spinal chordoma samples collected between December 2006 and September 2020. Clinical, histological, and radiological data were retrospectively analyzed and correlated to genetic findings. RESULTS: The authors identified homozygous deletions of CDKN2A/2B, PIK3CA mutations, and alterations affecting genes of SWI/SNF chromatin remodeling complexes (PBRM1 and ARID1A) as potential theranostic biomarkers. Using matched germline WES, they observed a higher frequency of a common genetic variant (rs2305089; p.(Gly177Asp)) in TBXT (97.8%, p < 0.001) compared to its distribution in the general population. PIK3CA mutation was identified as an independent biomarker of short progression-free survival (HR 10.68, p = 0.0008). Loss of CDKN2A/2B was more frequently observed in spinal tumors and recurrent tumors. CONCLUSIONS: In the current study, the authors identified driver events such as PBRM1 and PIK3CA mutations, TBXT alterations, or homozygous deletions of CDKN2A/2B, which could, for some, be considered potential theranostic markers and could allow for identifying novel therapeutic approaches. With the aim of a future biomolecular prognostication classification, alterations affecting PIK3CA and CDKN2A/2B could be considered as poor prognostic biomarkers.


Asunto(s)
Cordoma , Neoplasias de la Base del Cráneo , Neoplasias de la Columna Vertebral , Humanos , Pronóstico , Cordoma/patología , Neoplasias de la Columna Vertebral/genética , Medicina de Precisión , Estudios Retrospectivos , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Biomarcadores , Neoplasias de la Base del Cráneo/patología , Base del Cráneo/patología , Fosfatidilinositol 3-Quinasa Clase I/genética
16.
Eur J Nucl Med Mol Imaging ; 39(3): 450-60, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22183107

RESUMEN

PURPOSE: The purpose of this pilot study was to assess whether outcome in metastatic or recurrent breast cancer patients is related to metabolic response to endocrine therapy determined by (18)F-FDG PET/CT. METHODS: The study group comprised 22 patients with breast cancer (age 58 ± 11 years, mean ± SD) who were scheduled to receive endocrine therapy. They were systematically assessed by PET/CT at baseline and after a mean of 10 ± 4 weeks for evaluation of response after induction. All patients demonstrated FDG-avid lesions on the baseline PET/CT scan. The metabolic response was assessed according to EORTC criteria and based on the mean difference in SUV(max) between the two PET/CT scans, and the patients were classified into four groups: complete or partial metabolic response, or stable or progressive metabolic disease (CMR, PMR, SMD and PMD, respectively). All patients were followed in our institution. RESULTS: Metastatic sites were localized in bone (n = 15), lymph nodes (n = 11), chest wall (n = 3), breast (n = 5), lung (n = 3), soft tissue (n = 1) and liver (n = 1). PMR was observed in 11 patients (50%), SMD in 5 (23%) and PMD in 6 (27%). The median progression-free survival (PFS) times were 20, 27 and 6 months in the PMR, SMD and PMD groups, respectively. PFS in the SMD group differed from that in the PMR and SMD groups (p < 0.0001). CONCLUSION: Metabolic response assessed by FDG PET/CT imaging in patients with metastatic breast cancer treated with endocrine therapy is predictive of the patients' PFS.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Fluorodesoxiglucosa F18 , Hormonas/uso terapéutico , Imagen Multimodal , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Mucina-1/sangre , Metástasis de la Neoplasia , Proyectos Piloto , Recurrencia , Resultado del Tratamiento
17.
Med Phys ; 49(6): 3816-3829, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35302238

RESUMEN

BACKGROUND: Translation of predictive and prognostic image-based learning models to clinical applications is challenging due in part to their lack of interpretability. Some deep-learning-based methods provide information about the regions driving the model output. Yet, due to the high-level abstraction of deep features, these methods do not completely solve the interpretation challenge. In addition, low sample size cohorts can lead to instabilities and suboptimal convergence for models involving a large number of parameters such as convolutional neural networks. PURPOSE: Here, we propose a method for designing radiomic models that combines the interpretability of handcrafted radiomics with a sub-regional analysis. MATERIALS AND METHODS: Our approach relies on voxel-wise engineered radiomic features with average global aggregation and logistic regression. The method is illustrated using a small dataset of 51 soft tissue sarcoma (STS) patients where the task is to predict the risk of lung metastasis occurrence during the follow-up period. RESULTS: Using positron emission tomography/computed tomography and two magnetic resonance imaging sequences separately to build two radiomic models, we show that our approach produces quantitative maps that highlight the signal that contributes to the decision within the tumor region of interest. In our STS example, the analysis of these maps identified two biological patterns that are consistent with STS grading systems and knowledge: necrosis development and glucose metabolism of the tumor. CONCLUSIONS: We demonstrate how that method makes it possible to spatially and quantitatively interpret radiomic models amenable to sub-regions identification and biological interpretation for patient stratification.


Asunto(s)
Neoplasias Pulmonares , Sarcoma , Humanos , Neoplasias Pulmonares/patología , Imagen por Resonancia Magnética/métodos , Redes Neurales de la Computación , Tomografía Computarizada por Tomografía de Emisión de Positrones
18.
J Nucl Med ; 63(8): 1231-1238, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-34857663

RESUMEN

We aimed to predict the presence of vaccine-induced hypermetabolic lymph nodes (v-HLNs) on 18F-FDG PET/CT after coronavirus disease 2019 (COVID-19) vaccination and determine their association with lymphocyte counts. Methods: In this retrospective single-center study, we included consecutive patients who underwent 18F-FDG PET/CT imaging after messenger RNA- or viral vector-based COVID-19 vaccination between early March and late April 2021. Demographics, clinical parameters, and absolute lymphocyte count (ALC) were collected, and their association with the presence of v-HLNs in the draining territory was studied by logistic regression. Results: In total, 260 patients were eligible, including 209 (80%) women and 145 (56%) with breast cancer. The median age was 50 y (range, 23-96 y). The messenger RNA vaccine had been given to 233 (90%). Ninety (35%) patients had v-HLNs, with a median SUVmax of 3.7 (range, 2.0-26.3), and 74 (44%) displayed lymphopenia, with a median ALC of 1.4 × 109/L (range, 0.3-18.3 × 109/L). An age of no more than 50 y (odds ratio [OR], 2.2; 95% CI, 1.0-4.5), the absence of lymphopenia (OR, 2.2; 95% CI, 1.1-4.3), and less than a 30-d interval from the last vaccine injection to the 18F-FDG PET/CT (OR, 2.6; 95% CI, 1.3-5.6) were independent factors for v-HLNs on multivariate analysis. In breast cancer patients, the absence of lymphopenia was the only independent factor significantly associated with v-HLNs (OR, 2.9; 95% CI, 1.2-7.4). Conclusion: Patients with a normal ALC after COVID-19 vaccination were more likely to have v-HLNs on 18F-FDG PET/CT, both of which might be associated with a stronger immune response to vaccination.


Asunto(s)
Neoplasias de la Mama , Vacunas contra la COVID-19 , COVID-19 , Ganglios Linfáticos , Linfopenia , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Femenino , Fluorodesoxiglucosa F18 , Humanos , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Estudios Retrospectivos , Vacunación/efectos adversos , Adulto Joven , Vacunas de ARNm/efectos adversos
19.
Head Neck ; 44(11): 2452-2464, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35875934

RESUMEN

PURPOSE: To analyze outcomes of patients treated with curative reirradiation (reRT), with intensity-modulated radiation therapy (IMRT) or proton therapy (PT) for recurrent head and neck squamous cell carcinoma (HNSCC). MATERIALS: Among the 55 patients reirradiated for head and neck cancer from 30/08/2012 to 08/04/2019, 23 had HNSCC and received IMRT (52.2%) or PT (47.8%) at a median maximum dose to the CTV of 66 Gy. RESULTS: After a median follow-up of 41.3 months, 18 patients developed a locoregional recurrence (LR), of which eight (44.4%) occurred within the previously reirradiated volume. Two-year locoregional failure-free survival and overall survival were 18.3%[95%CI:7.1%-47.1%] and 42.5%[95%CI:26.2%-69.1%], respectively. Disease-free survival was significantly longer in the PT group (p = 0.031). Main late grade ≥2 toxicities were dysphagia and trismus. CONCLUSION: Curative reRT in HNSCC is possible for selected cases, but the LR rate in the irradiated field and the risk of toxicity grade ≥2 remain high.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Terapia de Protones , Radioterapia de Intensidad Modulada , Reirradiación , Neoplasias de Cabeza y Cuello/etiología , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Recurrencia Local de Neoplasia , Terapia de Protones/efectos adversos , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada/efectos adversos , Reirradiación/efectos adversos , Carcinoma de Células Escamosas de Cabeza y Cuello/etiología , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia
20.
J Surg Oncol ; 103(6): 602-6, 2011 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-21480254

RESUMEN

Hybrid systems associating the sharpness of anatomic images coming from computed tomography (CT) and radionuclide functional imaging (SPET or PET) are opening a new era in oncology. This multimodal imaging method is now routinely used for the diagnosis, extent, follow up, treatment response and detection of occult disease in different types of malignancies with a significant impact on the treatment strategy leading for a change for more than 68% of all investigated patients.


Asunto(s)
Neoplasias/diagnóstico por imagen , Tomografía de Emisión de Positrones , Tomografía Computarizada de Emisión de Fotón Único , Adulto , Anciano , Fluorodesoxiglucosa F18 , Humanos , Persona de Mediana Edad , Tumores Neuroendocrinos/diagnóstico por imagen , Radiofármacos , Sensibilidad y Especificidad , Neoplasias de la Tiroides/diagnóstico por imagen
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