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BACKGROUND: The use of scapular tip chimeric free flaps (STFFs) for reconstructing mandibular defects has recently become popular, but its utility relative to other bone-containing free flaps remains debatable. The aim of the report is to describe how technical modification of STFF impacted in its use for mandibular reconstruction also commenting results obtained in a unicentric series of patients. PATIENTS AND METHODS: Patients undergoing mandibular reconstruction using an STFF from January 1, 2014 to June 1, 2022 were retrospectively enrolled in this report. We collected data on chimeric flap type, bone management, vascular pedicles, and the final outcomes. In total, 31 patients (13 men and 18 women) with a mean age of 68 years were enrolled. According to the classification system of Urken, 15 patients had body defects, while 7 had ramus defects, another 7 had symphysis defects, and 2 had both ramus and bodily defects. STFF was always harvested working in two equips simultaneously, in supine position. Dissection included preparation of chimeric components of the flap as latissimus dorsi, serratus and scapular tip. After pedicle dissection scapular bone was cut basing on reconstructive needing with a rectangular (stick) shape including the border of the scapula. In cases of longer bone harvesting, circumflex pedicle was also included to perfuse the upper portion of the scapular border. In five cases, the STFF was harvested with only the scapular angle component, and was thus a composite osteomuscular flap; for the remaining 26 cases, a chimeric STFF was used. Circumflex pedicle was included for eight patients. Six of the seven patients with symphyseal defects underwent a single osteotomy. RESULTS: The average length of the harvested was 69.92 mm (maximum length = 104 mm). The average height of transplanted bone was 26.78 mm (maximum height = 44.2 mm). Mouth-opening was normal in 25 patients, limited in 6 patients, and severely impaired in no patients. The cosmetic results were rated as excellent by 20 patients, good by 8 patients, and poor by 3 patients. CONCLUSION: The STFF is an excellent option for mandibular reconstruction when other flaps are not available and for patients in poor general condition. Technical innovations here presented made possible to harvest long bone segments with accurate shape thanks to osteotomies if needed and with adequate soft tissues components of the chimeric flap, ensuring satisfactory functional and cosmetic results.
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Retalhos de Tecido Biológico , Reconstrução Mandibular , Procedimentos de Cirurgia Plástica , Masculino , Humanos , Feminino , Idoso , Retalhos de Tecido Biológico/transplante , Reconstrução Mandibular/métodos , Estudos Retrospectivos , Escápula/transplanteRESUMO
BACKGROUND: Oral squamous cell carcinoma (OSCC) treatment is based largely on the TNM stage. The eighth edition includes important new prognostic parameters (extranodal extension and depth of invasion), while it does not consider tumour molecular characteristics or minor invasion criteria (perineural and lymphovascular invasion, grading and resection margins). This study evaluated how well the TNM eighth edition predicts the biological behaviour of OSCC, considering survival and risk of locoregional recurrence. MATERIALS AND METHODS: Data from 217 patients treated for OSCC were analysed, including epidemiologic characteristics, histological features and treatment. RESULTS: No significant correlations with overall survival or tumour recurrence were found for pT stages and the type of treatment, while different pN stages had significant differences in recurrence, but not in overall survival. We found significant correlations between overall survival and tumour grade and lymphovascular and perineural invasion and a significant correlation between tumour resection margins and the risk of recurrence. CONCLUSIONS: The current TNM staging system is a necessary but not sufficient tool for predicting the overall survival and risk of recurrence of OSCC. It could be improved by considering other factors, such as minor invasion criteria and biological markers.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Estadiamento de Neoplasias , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/patologia , Margens de Excisão , Recidiva Local de Neoplasia/patologia , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/patologia , Estudos RetrospectivosRESUMO
OBJECTIVES: To identify and validate baseline magnetic resonance imaging (b-MRI) radiomic features (RFs) as predictors of disease outcomes in effectively cured head and neck squamous cell carcinoma (HNSCC) patients. MATERIALS AND METHODS: Training set (TS) and validation set (VS) were retrieved from preexisting datasets (HETeCo and BD2Decide trials, respectively). Only patients with both pre- and post-contrast enhancement T1 and T2-weighted b-MRI and at least 2 years of follow-up (FUP) were selected. The combination of the best extracted RFs was used to classify low risk (LR) vs. high risk (HR) of disease recurrence. Sensitivity, specificity, and area under the curve (AUC) of the radiomic model were computed on both TS and VS. Overall survival (OS) and 5-year disease-free survival (DFS) Kaplan-Meier (KM) curves were compared for LR vs. HR. The radiomic-based risk class was used in a multivariate Cox model, including well-established clinical prognostic factors (TNM, sub-site, human papillomavirus [HPV]). RESULTS: In total, 57 patients of TS and 137 of VS were included. Three RFs were selected for the signature. Sensitivity of recurrence risk classifier was 0.82 and 0.77, specificity 0.78 and 0.81, AUC 0.83 and 0.78 for TS and VS, respectively. VS KM curves for LR vs. HR groups significantly differed both for 5-year DFS (p<.0001) and OS (p=.0004). A combined model of RFs plus TNM improved prognostic performance as compared to TNM alone, both for VS 5-year DFS (C-index: 0.76 vs. 0.60) and OS (C-index: 0.74 vs. 0.64). CONCLUSIONS: Radiomics of b-MRI can help to predict recurrence and survival outcomes in HNSCC.
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Neoplasias de Cabeça e Pescoço , Recidiva Local de Neoplasia , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia/diagnóstico por imagem , Prognóstico , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagemRESUMO
PURPOSE: To compare diagnostic performance between computed tomography (CT) and magnetic resonance imaging (MRI) for the detection of bone infiltration from oral cancer, and to test interobserver agreement between radiologists with different expertises. MATERIALS AND METHODS: Pre-surgical CT and MRI were reviewed independently by two radiologists with different expertises in head and neck oncology. A third radiologist reviewed CT and MRI simultaneously. Interobserver agreement was calculated by Cohen test. Association between radiological evidence of bone infiltration and histological reference was tested by Fisher's exact test or Chi-squared test, as appropriate. Receiving operator curve was calculated and area under the curve (AUC) was compared between CT, MRI, and both methods together. RESULTS: Interobserver agreement was moderate: the trainee under-reported periosteal reaction on CT and inferior alveolar canal involvement on MRI. Imaging findings associated with histologic evidence of bone infiltration were: periosteal reaction and cortical erosion on CT; bone marrow involvement, contrast enhancement within bone; and inferior alveolar canal involvement on MRI. Sensitivity of MRI alone (74 %) was higher than CT (52 %). Simultaneous review of CT and MRI showed the highest specificity (91 %), with the increase of diagnostic performance in the subgroup of subjects with positive MRI (AUC = 0.689; p = 0.044). CONCLUSION: Higher expertise allows pre-surgical detection of clinically relevant signs of bone infiltration sensitivity of MRI alone is higher than CT for the detection of bone infiltration from oral cancer. In MRI positive cases, diagnostic integration with combined review of CT and MRI is suggested for optimal diagnostic performance.
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Competência Clínica , Neoplasias Mandibulares/diagnóstico por imagem , Neoplasias Mandibulares/secundário , Neoplasias Bucais/diagnóstico por imagem , Neoplasias Bucais/patologia , Meios de Contraste , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Tumour relapse is recognized to be the prime fatal burden in patients affected by head and neck squamous cell carcinoma (HNSCC), but no discrete molecular trait has yet been identified to make reliable early predictions of tumour recurrence. Expression of cell surface proteoglycans (PGs) is frequently altered in carcinomas and several of them are gradually emerging as key prognostic factors. METHODS: A PG expression analysis at both mRNA and protein level, was pursued on primary lesions derived from 173 HNSCC patients from whom full clinical history and 2 years post-surgical follow-up was accessible. Gene and protein expression data were correlated with clinical traits and previously proposed tumour relapse markers to stratify high-risk patient subgroups. RESULTS: HNSCC lesions were indeed found to exhibit a widely aberrant PG expression pattern characterized by a variable expression of all PGs and a characteristic de novo transcription/translation of GPC2, GPC5 and NG2/CSPG4 respectively in 36%, 72% and 71% on 119 cases. Importantly, expression of NG2/CSPG4, on neoplastic cells and in the intralesional stroma (Hazard Ratio [HR], 6.76, p = 0.017) was strongly associated with loco-regional relapse, whereas stromal enrichment of SDC2 (HR, 7.652, p = 0.007) was independently tied to lymphnodal infiltration and disease-related death. Conversely, down-regulated SDC1 transcript (HR, 0.232, p = 0.013) uniquely correlated with formation of distant metastases. Altered expression of PGs significantly correlated with the above disease outcomes when either considered alone or in association with well-established predictors of poor prognosis (i.e. T classification, previous occurrence of precancerous lesions and lymphnodal metastasis). Combined alteration of all three PGs was found to be a reliable predictor of shorter survival. CONCLUSIONS: An unprecedented PG-based prognostic portrait is unveiled that incisively diversifies disease course in HNSCC patients beyond the currently known clinical and molecular biomarkers.
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Antígenos/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Recidiva Local de Neoplasia/metabolismo , Proteoglicanas/metabolismo , Adulto , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Estimativa de Kaplan-Meier , Masculino , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Boca/metabolismo , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/prevenção & controle , Modelos de Riscos Proporcionais , Sindecana-2/metabolismo , Resultado do TratamentoRESUMO
PURPOSE: Given its biological and anatomic features, autologous bone is the first choice for cranioplasty after bone decompression. When autologous bone is not available or must be replaced, surgeons can choose among various materials to create an alloplastic cranioplasty. The Italian Society for Neurosurgery promoted a prospective study conducted at 4 Italian neurosurgical units to compare different methods of cranioplasty and to assess the clinical results and incidence of complications. MATERIALS AND METHODS: Patients older than 14 years who underwent repositioning of autologous bone or 3-dimensional image-guided reconstruction with prostheses made of an alloplastic material (polyetheretherketone, polymethylmethacrylate, or hydroxyapatite) after cranial decompression were enrolled prospectively from January 2008 through December 2013. The collected data included the material used to produce the prosthesis, the type of cranioplasty (primary or secondary), and complications that required surgical removal of the prosthesis (eg, infection, bone resorption, and fracture of the cranioplasty). RESULTS: Ninety-six patients met the study criteria. Fifty cases were reconstructed with hydroxyapatite, 31 with bone, 13 with polymethylmethacrylate, and 2 with polyetheretherketone. Seven patients (7.3%) developed complications related to the cranioplastic implant that required reoperation. These complications included infection (4 cases), bone resorption (2 cases), and fracture of the cranioplastic prosthesis (1 case). Statistical analysis showed a higher rate of complications with the use of autologous bone versus alloplastic materials (P = .03). Owing to the limited number of cases, no statistically meaningful complication was seen among the different alloplastic materials or when the cranioplastic implant was placed as secondary treatment. CONCLUSIONS: These data and those of other reports suggest that cranioplasty conducted using alloplastic 3-dimensional reconstruction materials have a lower rate of complications than those conducted using autologous bone.
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Procedimentos de Cirurgia Plástica/métodos , Crânio/cirurgia , Adulto , Idoso , Transplante Ósseo/efeitos adversos , Transplante Ósseo/métodos , Feminino , Humanos , Imageamento Tridimensional , Fixadores Internos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Procedimentos de Cirurgia Plástica/efeitos adversosRESUMO
The clinical applicability of radiomics in oncology depends on its transferability to real-world settings. However, the absence of standardized radiomics pipelines combined with methodological variability and insufficient reporting may hamper the reproducibility of radiomic analyses, impeding its translation to clinics. This study aimed to identify and replicate published, reproducible radiomic signatures based on magnetic resonance imaging (MRI), for prognosis of overall survival in head and neck squamous cell carcinoma (HNSCC) patients. Seven signatures were identified and reproduced on 58 HNSCC patients from the DB2Decide Project. The analysis focused on: assessing the signatures' reproducibility and replicating them by addressing the insufficient reporting; evaluating their relationship and performances; and proposing a cluster-based approach to combine radiomic signatures, enhancing the prognostic performance. The analysis revealed key insights: (1) despite the signatures were based on different features, high correlations among signatures and features suggested consistency in the description of lesion properties; (2) although the uncertainties in reproducing the signatures, they exhibited a moderate prognostic capability on an external dataset; (3) clustering approaches improved prognostic performance compared to individual signatures. Thus, transparent methodology not only facilitates replication on external datasets but also advances the field, refining prognostic models for potential personalized medicine applications.
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Neoplasias de Cabeça e Pescoço , Imageamento por Ressonância Magnética , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Imageamento por Ressonância Magnética/métodos , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/patologia , Feminino , Masculino , Reprodutibilidade dos Testes , Pessoa de Meia-Idade , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Idoso , Adulto , RadiômicaRESUMO
Introduction: Salivary gland cancers represent a rare heterogeneous group of neoplasms with complex clinicopathological characteristics and distinct biological behaviour. The appropriate diagnosis and management of parotid gland cancer are challenging and should be based on the clinical, imaging, cytological, and histological features. The present study analysed the use of preoperative fine-needle aspiration cytology (FNAC) and intraoperative frozen section (FS) to guide the appropriate surgical and postoperative treatment of parotid gland cancers. Materials and Methods: We selected 48 patients with primary malignancy of the parotid gland surgically treated between 1 January 2008 and 30 June 2017 at the Maxillo-Facial Surgery Division, University Hospital of Parma, Italy. The patients had postoperative histological diagnosis of malignant parotid cancer and were followed up for longer than 5 years. Results: The 48 patients included in this study had a mean age of 56.7 years. The most frequent type of parotid gland cancer was carcinoma ex pleomorphic adenoma (22.9%), followed by mucoepidermoid carcinoma (16.7%) and acinic cell carcinoma (14.6%). All 48 patients underwent preoperative FNAC: 29 (60.4%) and 19 (39.6%) were suggestive of malignant and benign lesions, respectively. In 31 patients, intraoperative FS was performed. Discussion: Compared to previous studies, the present study showed significantly lower diagnostic sensitivity of FNAC for parotid gland cancers. The preoperative diagnostic accuracy for suspected malignant cases may be improved by repeat analysis of the cytological specimen by experts, preoperative core needle biopsy, and/or intraoperative FS analysis of the suspected mass.
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BACKGROUND: . At present, the prognostic prediction in advanced oral cavity squamous cell carcinoma (OCSCC) is based on the tumor-node-metastasis (TNM) staging system, and the most used imaging modality in these patients is magnetic resonance image (MRI). With the aim to improve the prediction, we developed an MRI-based radiomic signature as a prognostic marker for overall survival (OS) in OCSCC patients and compared it with published gene expression signatures for prognosis of OS in head and neck cancer patients, replicated herein on our OCSCC dataset. METHODS: For each patient, 1072 radiomic features were extracted from T1 and T2-weighted MRI (T1w and T2w). Features selection was performed, and an optimal set of five of them was used to fit a Cox proportional hazard regression model for OS. The radiomic signature was developed on a multi-centric locally advanced OCSCC retrospective dataset (n = 123) and validated on a prospective cohort (n = 108). RESULTS: The performance of the signature was evaluated in terms of C-index (0.68 (IQR 0.66-0.70)), hazard ratio (HR 2.64 (95% CI 1.62-4.31)), and high/low risk group stratification (log-rank p < 0.001, Kaplan-Meier curves). When tested on a multi-centric prospective cohort (n = 108), the signature had a C-index of 0.62 (IQR 0.58-0.64) and outperformed the clinical and pathologic TNM stage and six out of seven gene expression prognostic signatures. In addition, the significant difference of the radiomic signature between stages III and IVa/b in patients receiving surgery suggests a potential association of MRI features with the pathologic stage. CONCLUSIONS: Overall, the present study suggests that MRI signatures, containing non-invasive and cost-effective remarkable information, could be exploited as prognostic tools.
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BACKGROUND AND PURPOSE: Prognosis in locally advanced head and neck cancer (HNC) is currently based on TNM staging system and tumor subsite. However, quantitative imaging features (i.e., radiomic features) from magnetic resonance imaging (MRI) may provide additional prognostic info. The aim of this work is to develop and validate an MRI-based prognostic radiomic signature for locally advanced HNC. MATERIALS AND METHODS: Radiomic features were extracted from T1- and T2-weighted MRI (T1w and T2w) using the segmentation of the primary tumor as mask. In total 1072 features (536 per image type) were extracted for each tumor. A retrospective multi-centric dataset (n = 285) was used for features selection and model training. The selected features were used to fit a Cox proportional hazard regression model for overall survival (OS) that outputs the radiomic signature. The signature was then validated on a prospective multi-centric dataset (n = 234). Prognostic performance for OS and disease-free survival (DFS) was evaluated using C-index. Additional prognostic value of the radiomic signature was explored. RESULTS: The radiomic signature had C-index = 0.64 for OS and C-index = 0.60 for DFS in the validation set. The addition of the radiomic signature to other clinical features (TNM staging and tumor subsite) increased prognostic ability for both OS (HPV- C-index 0.63 to 0.65; HPV+ C-index 0.75 to 0.80) and DFS (HPV- C-index 0.58 to 0.61; HPV+ C-index 0.64 to 0.65). CONCLUSION: An MRI-based prognostic radiomic signature was developed and prospectively validated. Such signature can successfully integrate clinical factors in both HPV+ and HPV- tumors.
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Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Humanos , Prognóstico , Estudos Retrospectivos , Estudos Prospectivos , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodosRESUMO
Central giant cell granulomas (CGCG) are rare intraosseous osteolytic lesions of uncertain aetiology. Despite the benign nature of this neoplasia, the lesions can rapidly grow and become large, painful, invasive, and destructive. The identification of molecular drivers could help in the selection of targeted therapies for specific cases. TRPV4, KRAS and FGFR1 mutations have been associated with these lesions but no correlation between the mutations and patient features was observed so far. In this study, we analysed 17 CGCG cases of an Italian cohort and identified an interesting and significant (p=0.0021) correlation between FGFR1 mutations and age. In detail, FGFR1 mutations were observed frequently and exclusively in CGCG from young (<18 years old) patients (4/5 lesions, 80%). Furthermore, the combination between ours and previously published data confirmed a significant difference in the frequency of FGFR1 mutations in CGCG from patients younger than 18 years at the time of diagnosis (9/23 lesions, 39%) when compared to older patients (1/31 lesions, 0.03%; p=0.0011), thus corroborating our observation in a cohort of 54 patients. FGFR1 variants in young CGCG patients could favour fast lesion growth, implying that they seek medical attention earlier. Our observation might help prioritise candidates for FGFR1 testing, thus opening treatment options with FGFR inhibitors.
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Granuloma de Células Gigantes , Humanos , Adolescente , Granuloma de Células Gigantes/genética , Granuloma de Células Gigantes/diagnóstico , Granuloma de Células Gigantes/patologia , Taxa de Mutação , Mutação , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genéticaRESUMO
Background: Treatment decision-making in oropharyngeal squamous cell carcinoma (OPSCC) includes clinical stage, HPV status, and smoking history. Despite improvements in staging with separation of HPV-positive and -negative OPSCC in AJCC 8th edition (AJCC8), patients are largely treated with a uniform approach, with recent efforts focused on de-intensification in low-risk patients. We have previously shown, in a pooled analysis, that the genomic adjusted radiation dose (GARD) is predictive of radiation treatment benefit and can be used to guide RT dose selection. We hypothesize that GARD can be used to predict overall survival (OS) in HPV-positive OPSCC patients treated with radiotherapy (RT). Methods: Gene expression profiles (Affymetrix Clariom D) were analyzed for 234 formalin-fixed paraffin-embedded samples from HPV-positive OPSCC patients within an international, multi-institutional, prospective/retrospective observational study including patients with AJCC 7th edition stage III-IVb. GARD, a measure of the treatment effect of RT, was calculated for each patient as previously described. In total, 191 patients received primary RT definitive treatment (chemoradiation or RT alone, and 43 patients received post-operative RT. Two RT dose fractionations were utilized for primary RT cases (70 Gy in 35 fractions or 69.96 Gy in 33 fractions). Median RT dose was 70 Gy (range 50.88-74) for primary RT definitive cases and 66 Gy (range 44-70) for post-operative RT cases. The median follow up was 46.2 months (95% CI, 33.5-63.1). Cox proportional hazards analyses were performed with GARD as both a continuous and dichotomous variable and time-dependent ROC analyses compared the performance of GARD with the NRG clinical nomogram for overall survival. Results: Despite uniform radiation dose utilization, GARD showed significant heterogeneity (range 30-110), reflecting the underlying genomic differences in the cohort. On multivariable analysis, each unit increase in GARD was associated with an improvement in OS (HR = 0.951 (0.911, 0.993), p = 0.023) compared to AJCC8 (HR = 1.999 (0.791, 5.047)), p = 0.143). ROC analysis for GARD at 36 months yielded an AUC of 80.6 (69.4, 91.9) compared with an AUC of 73.6 (55.4, 91.7) for the NRG clinical nomogram. GARD≥64.2 was associated with improved OS (HR = 0.280 (0.100, 0.781), p = 0.015). In a virtual trial, GARD predicts that uniform RT dose de-escalation results in overall inferior OS but proposes two separate genomic strategies where selective RT dose de-escalation in GARD-selected populations results in clinical equipoise. Conclusions: In this multi-institutional cohort of patients with HPV-positive OPSCC, GARD predicts OS as a continuous variable, outperforms the NRG nomogram and provides a novel genomic strategy to modern clinical trial design. We propose that GARD, which provides the first opportunity for genomic guided personalization of radiation dose, should be incorporated in the diagnostic workup of HPV-positive OPSCC patients.
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BACKGROUND: There is significant interest in treatment de-escalation for human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) patients given the generally favourable prognosis. However, 15-30% of patients recur after primary treatment, reflecting a need for improved risk-stratification tools. We sought to develop a molecular test to risk stratify HPV+ OPSCC patients. METHODS: We created an immune score (UWO3) associated with survival outcomes in six independent cohorts comprising 906 patients, including blinded retrospective and prospective external validations. Two aggressive radiation de-escalation cohorts were used to assess the ability of UWO3 to identify patients who recur. Multivariate Cox models were used to assess the associations between the UWO3 immune class and outcomes. FINDINGS: A three-gene immune score classified patients into three immune classes (immune rich, mixed, or immune desert) and was strongly associated with disease-free survival in six datasets, including large retrospective and prospective datasets. Pooled analysis demonstrated that the immune rich group had superior disease-free survival compared to the immune desert (HR = 9.0, 95% CI: 3.2-25.5, P = 3.6 × 10-5) and mixed (HR = 6.4, 95% CI: 2.2-18.7, P = 0.006) groups after adjusting for age, sex, smoking status, and AJCC8 clinical stage. Finally, UWO3 was able to identify patients from two small treatment de-escalation cohorts who remain disease-free after aggressive de-escalation to 30 Gy radiation. INTERPRETATION: With additional prospective validation, the UWO3 score could enable biomarker-driven clinical decision-making for patients with HPV+ OPSCC based on robust outcome prediction across six independent cohorts. Prospective de-escalation and intensification clinical trials are currently being planned. FUNDING: CIHR, European Union, and the NIH.
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Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Infecções por Papillomavirus/complicações , Estudos Retrospectivos , Recidiva Local de Neoplasia , Neoplasias Orofaríngeas/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Prognóstico , Biomarcadores , Papillomavirus Humano , PapillomaviridaeRESUMO
OBJECTIVES: The prognostic advantage of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) resulted in the initiation of treatment de-intensification studies. Two randomized controlled trials (RCTs) reported inferior survival of HPV-positive OPSCC treated with radiotherapy plus cetuximab compared to standard of care radiotherapy plus cisplatin. In this study we investigated whether the important role of cisplatin in the treatment of HPV-positive OPSCCs would also emerge from causal inference analyses of real-world data. MATERIAL AND METHODS: A retrospective cohort of 263 advanced-stage OPSCC-patients from 5 European clinics was studied, treated with radiotherapy (RT) alone or cisplatin-based chemoradiotherapy (CRT) based on standard clinical indications. Causal inference was applied to adjust for treatment assignment, thereby simulating a randomized setting. Average treatment effect of concurrent cisplatin on overall survival (OS) probability was estimated using Bayesian Additive Regression Trees (BART) and Bayesian logistic regression. RESULTS: Significantly better survival probabilities were found for HPV-positive OPSCC treated with CRT compared to RT alone (3-year OS probability 0.961 versus 0.798, p = 0.008). CONCLUSION: This study using causal inference of retrospective patient data confirms the important role of cisplatin in the treatment of HPV-positive OPSCC. Causal inference analyses of real-world data complements the evidence from the published RCTs.
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Cisplatino , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Carcinoma de Células Escamosas de Cabeça e Pescoço , Quimiorradioterapia , Cisplatino/uso terapêutico , Análise de Dados , Humanos , Neoplasias Orofaríngeas/tratamento farmacológico , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/complicações , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologiaRESUMO
Under common therapeutic regimens, the prognosis of human papillomavirus (HPV)-positive squamous oropharyngeal carcinomas (OPCs) is more favorable than HPV-negative OPCs. However, the prognosis of some tumors is dismal, and validated prognostic factors are missing in clinical practice. The present work aimed to validate the prognostic significance of our published three-cluster model and to compare its prognostic value with those of the 8th edition of the tumor-node-metastasis staging system (TNM8) and published signatures and clustering models. METHODS: Patients with HPV DNA-positive OPCs with locoregionally advanced nonmetastatic disease treated with curative intent (BD2Decide observational study, NCT02832102) were considered as validation cohort. Patients were treated in seven European centers, with expertise in the multidisciplinary management of patients with head and neck cancer. The median follow-up was 46.2 months (95% CI, 41.2 to 50), and data collection was concluded in September 2019. The primary end point of this study was overall survival (OS). Three-clustering models and seven prognostic signatures were compared with our three-cluster model. RESULTS: The study population consisted of 235 patients. The three-cluster model confirmed its prognostic value. Two-year OS in each cluster was 100% in the low-risk cluster, 96.6% in the intermediate-risk cluster, and 86.3% in the high-risk cluster (P = .00074). For the high-risk cluster, we observed an area under the curve = 0.832 for 2-year OS, significantly outperforming TNM 8th edition (area under the curve = 0.596), and functional and biological differences were identified for each cluster. CONCLUSION: The rigorous clinical selection of the cases included in this study confirmed the robustness of our three-cluster model in HPV-positive OPCs. The prognostic value was found to be independent and superior compared with TNM8. The next step includes the translation of the three-cluster model in clinical practice. This could open the way to future exploration of already available therapies in HPV-positive OPCs tailoring de-escalation or intensification according to the three-cluster model.
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Alphapapillomavirus , Neoplasias de Cabeça e Pescoço , Expressão Gênica , Humanos , Estadiamento de Neoplasias , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genéticaRESUMO
BACKGROUND: Locoregionally advanced head and neck squamous cell carcinoma (HNSCC) patients have high relapse and mortality rates. Imaging-based decision support may improve outcomes by optimising personalised treatment, and support patient risk stratification. We propose a multifactorial prognostic model including radiomics features to improve risk stratification for advanced HNSCC, compared to TNM eighth edition, the gold standard. PATIENT AND METHODS: Data of 666 retrospective- and 143 prospective-stage III-IVA/B HNSCC patients were collected. A multivariable Cox proportional-hazards model was trained to predict overall survival (OS) using diagnostic CT-based radiomics features extracted from the primary tumour. Separate analyses were performed using TNM8, tumour volume, clinical and biological variables, and combinations thereof with radiomics features. Patient risk stratification in three groups was assessed through Kaplan-Meier (KM) curves. A log-rank test was performed for significance (p-value < 0.05). The prognostic accuracy was reported through the concordance index (CI). RESULTS: A model combining an 11-feature radiomics signature, clinical and biological variables, TNM8, and volume could significantly stratify the validation cohort into three risk groups (p < 0â01, CI of 0.79 as validation). CONCLUSION: A combination of radiomics features with other predictors can predict OS very accurately for advanced HNSCC patients and improves on the current gold standard of TNM8.
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BACKGROUND: Despite advances in treatments, 30% to 50% of stage III-IV head and neck squamous cell carcinoma (HNSCC) patients relapse within 2 years after treatment. The Big Data to Decide (BD2Decide) project aimed to build a database for prognostic prediction modeling. METHODS: Stage III-IV HNSCC patients with locoregionally advanced HNSCC treated with curative intent (1537) were included. Whole transcriptomics and radiomics analyses were performed using pretreatment tumor samples and computed tomography/magnetic resonance imaging scans, respectively. RESULTS: The entire cohort was composed of 71% male (1097)and 29% female (440): oral cavity (429, 28%), oropharynx (624, 41%), larynx (314, 20%), and hypopharynx (170, 11%); median follow-up 50.5 months. Transcriptomics and imaging data were available for 1284 (83%) and 1239 (80%) cases, respectively; 1047 (68%) patients shared both. CONCLUSIONS: This annotated database represents the HNSCC largest available repository and will enable to develop/validate a decision support system integrating multiscale data to explore through classical and machine learning models their prognostic role.
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Big Data , Neoplasias de Cabeça e Pescoço , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Recidiva Local de Neoplasia/genética , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/genéticaRESUMO
BACKGROUND: Sentinel node biopsy (SNB) may represent an alternative to elective neck dissection for the staging of patients with early head and neck squamous cell carcinoma (HNSCC). To date, the technique has been successfully described in a number of small single-institution studies. This report describes the long-term follow-up of a large European multicenter trial evaluating the accuracy of the technique. METHODS: A total of 227 SNB procedures were carried out across 6 centers, of which 134 were performed in clinically T1/2 N0 patients. All patients underwent SNB with preoperative lymphoscintigraphy, intraoperative blue dye, and handheld gamma probe. Sentinel nodes were evaluated with hematoxylin and eosin (H&E) staining, step-serial sectioning (SSS), and immunohistochemistry (IHC). There were 79 patients who underwent SNB as the sole staging tool, while 55 patients underwent SNB-assisted elective neck dissection. RESULTS: Sentinel nodes were successfully identified in 125 of 134 patients (93%), with a lower success rate observed for floor-of-mouth tumors (FoM; 88% vs. 96%, P = 0.138). Also, 42 patients were upstaged (34%); of these, 10 patients harbored only micrometastatic disease. At a minimum follow-up of 5 years, the overall sensitivity of SNB was 91%. The sensitivity and negative predictive values (NPV) were lower for patients with FoM tumors compared with other sites (80% vs. 97% and 88% vs. 98%, respectively, P = 0.034). CONCLUSIONS: Sentinel node biopsy is a reliable and reproducible means of staging the clinically N0 neck for patients with cT1/T2 HNSCC. It can be used as the sole staging tool for the majority of these patients, but cannot currently be recommended for patients with tumors in the floor of the mouth.
Assuntos
Carcinoma de Células Escamosas/secundário , Neoplasias de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas/cirurgia , Europa (Continente) , Seguimentos , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Técnicas Imunoenzimáticas , Metástase Linfática , Prognóstico , Sensibilidade e Especificidade , Biópsia de Linfonodo Sentinela , Taxa de SobrevidaRESUMO
[This corrects the article DOI: 10.1371/journal.pone.0232639.].
RESUMO
INTRODUCTION: In this study, we investigate the role of radiomics for prediction of overall survival (OS), locoregional recurrence (LRR) and distant metastases (DM) in stage III and IV HNSCC patients treated by chemoradiotherapy. We hypothesize that radiomic analysis of (peri-)tumoral tissue may detect invasion of surrounding tissues indicating a higher chance of locoregional recurrence and distant metastasis. METHODS: Two comprehensive data sources were used: the Dutch Cancer Society Database (Alp 7072, DESIGN) and "Big Data To Decide" (BD2Decide). The gross tumor volumes (GTV) were delineated on contrast-enhanced CT. Radiomic features were extracted using the RadiomiX Discovery Toolbox (OncoRadiomics, Liege, Belgium). Clinical patient features such as age, gender, performance status etc. were collected. Two machine learning methods were chosen for their ability to handle censored data: Cox proportional hazards regression and random survival forest (RSF). Multivariable clinical and radiomic Cox/ RSF models were generated based on significance in univariable cox regression/ RSF analyses on the held out data in the training dataset. Features were selected according to a decreasing hazard ratio for Cox and relative importance for RSF. RESULTS: A total of 444 patients with radiotherapy planning CT-scans were included in this study: 301 head and neck squamous cell carcinoma (HNSCC) patients in the training cohort (DESIGN) and 143 patients in the validation cohort (BD2DECIDE). We found that the highest performing model was a clinical model that was able to predict distant metastasis in oropharyngeal cancer cases with an external validation C-index of 0.74 and 0.65 with the RSF and Cox models respectively. Peritumoral radiomics based prediction models performed poorly in the external validation, with C-index values ranging from 0.32 to 0.61 utilizing both feature selection and model generation methods. CONCLUSION: Our results suggest that radiomic features from the peritumoral regions are not useful for the prediction of time to OS, LR and DM.