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PURPOSE: To establish and validate a delta-radiomics-based model for predicting progression-free survival (PFS) in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) following induction chemotherapy (IC). METHODS AND MATERIALS: A total of 250 LA-NPC patients (training cohort: n = 145; validation cohort: n = 105) were enrolled. Radiomic features were extracted from MRI scans taken before and after IC, and changes in these features were calculated. Following feature selection, a delta-radiomics signature was constructed using LASSO-Cox regression analysis. A prognostic nomogram incorporating independent clinical indicators and the delta-radiomics signature was developed and assessed for calibration and discrimination. Risk stratification by the nomogram was evaluated using Kaplan-Meier methods. RESULTS: The delta-radiomics signature, consisting of 12 features, was independently associated with prognosis. The nomogram, integrating the delta-radiomics signature and clinical factors demonstrated excellent calibration and discrimination. The model achieved a Harrell's concordance index (C-index) of 0.848 in the training cohort and 0.820 in the validation cohort. Risk stratification identified two groups with significantly different PFS rates. The three-year PFS for high-risk patients who received concurrent chemoradiotherapy (CCRT) or radiotherapy plus adjuvant chemotherapy (RT+AC) after IC was significantly higher than for those who received RT alone, reaching statistical significance. In contrast, for low-risk patients, the three-year PFS after IC was slightly higher for those who received CCRT or RT+AC compared to those who received RT alone; however, this difference did not reach statistical significance. CONCLUSIONS: Our delta MRI-based radiomics model could be useful for predicting PFS and may guide subsequent treatment decisions after IC in LA-NPC.
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Quimioterapia de Indução , Imageamento por Ressonância Magnética , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Nomogramas , Radiômica , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Quimioterapia de Indução/métodos , Imageamento por Ressonância Magnética/métodos , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/radioterapia , Prognóstico , Resultado do TratamentoRESUMO
Locally recurrent nasopharyngeal carcinoma (NPC) presents substantial challenges in clinical management. Although postoperative re-irradiation (re-RT) has been acknowledged as a potential treatment option, standardized guidelines and consensus regarding the use of re-RT in this context are lacking. This article provides a comprehensive review and summary of international recommendations on postoperative management for potentially resectable locally recurrent NPC, with a special focus on postoperative re-RT. A thorough search was conducted to identify relevant studies on postoperative re-RT for locally recurrent NPC. Controversial issues, including resectability criteria, margin assessment, indications for postoperative re-RT, and the optimal dose and method of re-RT, were addressed through a Delphi consensus process. The consensus recommendations emphasize the need for a clearer and broader definition of resectability, highlighting the importance of achieving clear surgical margins, preferably through an en bloc approach with frozen section margin assessment. Furthermore, these guidelines suggest considering re-RT for patients with positive or close margins. Optimal postoperative re-RT doses typically range around 60 Gy, and hyperfractionation has shown promise in reducing toxicity. These guidelines aim to assist clinicians in making evidence-based decisions and improving patient outcomes in the management of potentially resectable locally recurrent NPC. By addressing key areas of controversy and providing recommendations on resectability, margin assessment, and re-RT parameters, these guidelines serve as a valuable resource for clinical experts involved in the treatment of locally recurrent NPC.
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Background: Induction chemotherapy (IC) combined with concurrent chemoradiotherapy has become the standard treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Data on the prognostic value of the lymph node-to-primary tumor ratio (NTR) of positron emission tomography (PET) standardized uptake value (SUV) for patients treated with IC were limited. Objectives: To evaluate the prognostic value of the SUV NTR for patients with LA-NPC treated with IC. Design: In all, 467 patients with pretreatment 18F-fluorodeoxyglucose PET/computed tomography (CT) scans between September 2017 and November 2020 were retrospectively reviewed. Methods: The receiver operating characteristic (ROC) analysis was used to determine the optimal cut-off value of SUV NTR. Kaplan-Meier method was used to evaluate survival rates. The recursive partitioning analysis (RPA) was performed to construct a risk stratification model. Results: The optimal cutoff value of SUV NTR was 0.74. Multivariate analyses showed that SUV NTR and overall stage were independent predictors for distant metastasis-free survival (DMFS) and regional recurrent-free survival (RRFS). Therefore, an RPA model based on the endpoint of DMFS was generated and categorized the patients into three distinct risk groups: RPA I (low risk: SUV NTR < 0.74 and stage III), RPA II (medium risk: SUV NTR < 0.74 and stage IVa, or SUV NTR ⩾ 0.74 and stage III), and RPA III (high risk: SUV NTR ⩾ 0.74 and stage IVa), with a 3-year DMFS of 98.9%, 93.4%, and 84.2%, respectively. ROC analysis showed that the RPA model had superior predictive efficacy than the SUV NTR or overall stage alone. Conclusion: SUV NTR was an independent prognosticator for distant metastasis and regional recurrence in locoregionally advanced NPC. The RPA risk stratification model based on SUV NTR provides improved DMFS and RRFS prediction over the eighth edition of the TNM (Tumor Node Metastasis) staging system.
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OBJECTIVE: To analyze the interrelation between radiation dose and radiation-induced nasopharyngeal ulcer (RINU) in locoregional recurrent nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). METHODS: Clinical data were collected from 363 patients with locoregional recurrent NPC who received re-irradiated with definitive IMRT from 2009 to 2017. Twenty-nine patients were diagnosed with RINU. Univariate and multivariate analyses were used to re-evaluate the first and second radiotherapy plans and to identify predictive dosimetric factors. RESULTS: All dosimetric parameters were notably associated with the progression to RINU (p < 0.01) using paired samples Wilcoxon signed rank tests. Multivariate analysis showed that EQD2_ [Formula: see text]D80 (dose for 80 percent volume of the unilateral nasopharynx lesion) was an independent prognostic factor for RINU (p = 0.001). The area under the ROC curve for EQD2_ [Formula: see text]D80 was 0.846 (p < 0.001), and the cutoff point of 137.035 Gy could potentially be the dose tolerance of the nasopharyngeal mucosa. CONCLUSIONS: The sum of equivalent dose in 2 Gy fractions (EQD2) in the overlapping volumes between initial and re-irradiated nasopharyngeal mucosal tissue can be effective in predicting the hazard of developing RINU in NPC patients undergoing radical reirradiation with IMRT and we propose a EQD2_ [Formula: see text]D80 threshold of 137.035 Gy for the nasopharynx.
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Neoplasias Nasofaríngeas , Lesões por Radiação , Radiodermite , Radioterapia de Intensidade Modulada , Reirradiação , Humanos , Carcinoma Nasofaríngeo/radioterapia , Radioterapia de Intensidade Modulada/efeitos adversos , Neoplasias Nasofaríngeas/patologia , Úlcera/etiologia , Dosagem Radioterapêutica , Lesões por Radiação/etiologia , Estudos Retrospectivos , Nasofaringe/patologia , Radiodermite/etiologiaRESUMO
BACKGROUND: Post-radiation nasopharyngeal necrosis (PRNN) is a severe adverse event following re-radiotherapy for patients with locally recurrent nasopharyngeal carcinoma (LRNPC) and associated with decreased survival. Biological heterogeneity in recurrent tumors contributes to the different risks of PRNN. Radiomics can be used to mine high-throughput non-invasive image features to predict clinical outcomes and capture underlying biological functions. We aimed to develop a radiogenomic signature for the pre-treatment prediction of PRNN to guide re-radiotherapy in patients with LRNPC. METHODS: This multicenter study included 761 re-irradiated patients with LRNPC at four centers in NPC endemic area and divided them into training, internal validation, and external validation cohorts. We built a machine learning (random forest) radiomic signature based on the pre-treatment multiparametric magnetic resonance images for predicting PRNN following re-radiotherapy. We comprehensively assessed the performance of the radiomic signature. Transcriptomic sequencing and gene set enrichment analyses were conducted to identify the associated biological processes. RESULTS: The radiomic signature showed discrimination of 1-year PRNN in the training, internal validation, and external validation cohorts (area under the curve (AUC) 0.713-0.756). Stratified by a cutoff score of 0.735, patients with high-risk signature had higher incidences of PRNN than patients with low-risk signature (1-year PRNN rates 42.2-62.5% vs. 16.3-18.8%, P < 0.001). The signature significantly outperformed the clinical model (P < 0.05) and was generalizable across different centers, imaging parameters, and patient subgroups. The radiomic signature had prognostic value concerning its correlation with PRNN-related deaths (hazard ratio (HR) 3.07-6.75, P < 0.001) and all causes of deaths (HR 1.53-2.30, P < 0.01). Radiogenomics analyses revealed associations between the radiomic signature and signaling pathways involved in tissue fibrosis and vascularity. CONCLUSIONS: We present a radiomic signature for the individualized risk assessment of PRNN following re-radiotherapy, which may serve as a noninvasive radio-biomarker of radiation injury-associated processes and a useful clinical tool to personalize treatment recommendations for patients with LANPC.
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Neoplasias Nasofaríngeas , Recidiva Local de Neoplasia , Humanos , Carcinoma Nasofaríngeo/genética , Estudos Retrospectivos , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/genética , Prognóstico , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/radioterapia , Imageamento por Ressonância Magnética/métodosRESUMO
PURPOSE: To identify the prognostic value of the nodal features, propose a nomogram-based N stage system and evaluate the performance of seven N stage schemes of nasopharyngeal carcinoma (NPC) patients. METHODS: Data from 1638 non-distant metastatic NPC patients were used to develop nomograms predicting 3-year and 5-year overall survival (OS) and distant metastasis-free survival (DMFS). Based on nomogram and multivariate analyses, a new N-stage scheme was proposed. The performance of the nomogram-based N staging system was assessed against five newly proposed N staging systems and the current 8th N staging system using a quantitative model to compare hazard consistency, discrimination, outcome prediction, and sample size balance. The Kaplan-Meier method with log-rank tests was used to compare survival differences. RESULTS: Nomograms to predict OS and DMFS were constructed using extranodal extension infiltrating the surrounding structures (ENEmax), maximal axial diameter (MAD), large retropharyngeal lymph nodes (RLN, minimal axial diameter > 1.5 cm), multiple central nodal necrosis (CNN), and total lymph node (LN) number and level. Multivariate analysis showed the independent prognostic value of ENEmax and MAD > 3 cm for all selected survival endpoints (p < 0.05). Large RLN and lower neck involvement were independently associated with OS (p < 0.05). We proposed using a large RLN and MAD > 3 cm as N2 factors, and ENEmax and lower neck involvement as N3 factors. Among the seven N-stage schemes, our nomogram-based N scheme and ENEmax to N3 scheme (ENE3) ranked in the top two in the overall comparison with the elevated outcome predicting value (highest c-index). However, between the N0, N1, N1, and N2 subgroups, the ENE3 scheme showed no difference in OS or DMFS (p > 0.05). CONCLUSION: The predictive model highlighted the independent prognostic value of ENEmax, cervical lymph node, MAD, and large RLN, which can be used as criteria for future N staging.
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Neoplasias Nasofaríngeas , Nomogramas , Humanos , Carcinoma Nasofaríngeo/patologia , Prognóstico , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Metástase Linfática/patologia , Imageamento por Ressonância Magnética , Linfonodos/patologiaRESUMO
BACKGROUND: To evaluate the prognostic value of plasma Epstein-Barr virus (EBV) DNA level post-induction chemotherapy (IC) for patients with nasopharyngeal carcinoma (NPC). METHODS: A total of 893 newly diagnosed NPC patients treated with IC were retrospectively reviewed. The recursive partitioning analysis (RPA) was performed to construct a risk stratification model. The receiver operating characteristic (ROC) analysis was applied to determine the optimal cut-off value of post-IC EBV DNA. RESULTS: Post-IC EBV DNA levels and overall stage were independent predictors for distant metastasis-free survival (DMFS), overall survival (OS), and progression-free survival (PFS). The RPA model base on post-IC EBV DNA and overall stage categorized the patients into three distinct risk groups: RPA I (low-risk: stage II-III and post-IC EBV DNA < 200 copies/mL), RPA II (median-risk: stage II-III and post-IC EBV DNA ≥ 200 copies/mL, or stage IVA and post-IC EBV DNA < 200 copies/mL), and RPA III (high-risk: stage IVA and post-IC EBV DNA ≥ 200 copies/mL), with 3-year PFS of 91.1%, 82.6%, and 60.2%, respectively (p < 0.001). The DMFS and OS rates in different RPA groups were also distinct. The RPA model showed better risk discrimination than either the overall stage or post-RT EBV DNA alone. CONCLUSIONS: Plasma EBV DNA level post-IC was a robust prognostic biomarker for NPC. We developed an RPA model that provides improved risk discrimination over the 8th edition of the TNM staging system by integrating the post-IC EBV DNA level and the overall stage.
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Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/patologia , Prognóstico , Herpesvirus Humano 4/genética , Infecções por Vírus Epstein-Barr/complicações , Quimioterapia de Indução , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Estudos Retrospectivos , DNA Viral , Medição de RiscoRESUMO
BACKGROUND: To review our long-term clinical experience, analyze the failure patterns, and give suggestions for target volume delineation of carcinoma showing thymus-like differentiation (CASTLE) treated with intensity-modulated radiotherapy (IMRT). METHODS: From April 2008 to May 2019, 30 patients with CASTLE treated by postoperative or radical IMRT in our center were retrospectively reviewed. A total dose of 56-60 Gy in 28-30 fractions was prescribed to patients without residual disease and 66 Gy in 33 fractions for patients with residual or unresectable disease. Survival rates were calculated using the Kaplan-Meier method. Treatment-related toxicities were graded by National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0. RESULTS: Among the 30 patients, 12 (40%) received partial resection or biopsy. Lateral lymph node metastasis was observed in 7 (23.3%) patients. During follow-up, regional lymph node recurrence occurred in 2 patients and distant metastasis in 5 patients. With a median follow-up time of 63.5 months, the 5-year local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), overall survival (OS) and progression-free survival (PFS) rates were 100, 88.9, 78.9, 93.1 and 78.9%, respectively. For patients with no lateral neck node metastasis, prophylactic radiotherapy for lateral neck nodal regions failed to improve RRFS (p = 0.381) and OS (p = 0.153). CONCLUSION: Distant metastasis was the major failure pattern for CASTLE after surgery and IMRT. For patients with no lateral neck node metastasis, the omission of irradiation for lateral neck nodal regions seems to be safe and feasible.
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Carcinoma , Radioterapia de Intensidade Modulada , Humanos , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Carcinoma/patologia , Planejamento da Radioterapia Assistida por Computador/métodos , Metástase Linfática/radioterapiaRESUMO
BACKGROUND: The role of surgery in nasopharyngeal carcinoma liver metastases (NCLM) remains elusive, and the current application is limited. We aim to investigate whether hepatic resection (HR) of NCLM improves survival compared with non-hepatic resection (NHR) treatment. METHODS: One hundred and thirty-three patients with NCLM from 2007 to 2017 were divided into two groups. Propensity score matching (PSM) analysis was used to compare the clinical outcomes. RESULTS: After PSM the median overall survival (OS) and the 1, 3 and 5-year OS rates in HR group were 32.60 months, 86.2%, 37.3% and 37.3%, respectively; while for NHR group these values were 19.57 months, 61.5%, 12.9% and 2.9%, respectively (P = 0.008). Multivariate analysis indicated hepatitis B virus infection (P = 0.029) and hepatic resection (P = 0.018) were independent prognostic factors. CONCLUSION: Our study revealed that hepatectomy yields a survival benefit safely compared with systemic treatments, especially for patients with the size of largest metastasis < 5 cm, unilobar distribution of liver tumor and received unanatomical hepatectomy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/cirurgia , Neoplasias Hepáticas/secundário , Hepatectomia , Pontuação de Propensão , Neoplasias Nasofaríngeas/cirurgia , Estudos Retrospectivos , Prognóstico , Carcinoma Hepatocelular/cirurgiaRESUMO
Nasopharyngeal carcinoma (NPC) has a 10-15% recurrence rate, while no long term or durable treatment options are currently available. Single-cell profiling in recurrent NPC (rNPC) may aid in designing effective anticancer therapies, including immunotherapies. For the first time, we profiled the transcriptomes of â¼60,000 cells from four primary NPC and two rNPC cases to provide deeper insights into the dynamic changes in rNPC within radiation fields. Heterogeneity of both immune cells (T, natural killer, B, and myeloid cells) and tumor cells was characterized. Recurrent samples showed increased infiltration of regulatory T cells in a highly immunosuppressive state and CD8+ T cells in a highly cytotoxic and dysfunctional state. Enrichment of M2-polarized macrophages and LAMP3+ dendritic cells conferred enhanced immune suppression to rNPC. Furthermore, malignant cells showed enhanced immune-related features, such as antigen presentation. Elevated regulatory T cell levels were associated with a worse prognosis, with certain receptor-ligand communication pairs identified in rNPC. Even with relatively limited samples, our study provides important clues to complement the exploitation of rNPC immune environment and will help advance targeted immunotherapy of rNPC.
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Neoplasias Nasofaríngeas , Linfócitos T CD8-Positivos , Humanos , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/terapia , Recidiva Local de Neoplasia/genética , Análise de Sequência de RNA , Microambiente Tumoral/genéticaRESUMO
BACKGROUND: The delineation of target volume after induction chemotherapy(IC) for nasopharyngeal carcinoma(NPC) is currently controversial. In this study, we aimed to analyze the long-term local control(LC) and failure patterns of T4 NPC treated with reduced target volume radiotherapy after IC. METHODS: From September 2007 to January 2013, 145 patients with T4 NPC were retrospectively reviewed. All patients received at least 1 cycle of IC followed by intensity modulated radiotherapy(IMRT). The gross tumor volume(GTV) was delineated according to the post-IC images for intracavity tumors and lymph nodes. The LC and overall survival (OS) rates were calculated using the Kaplan-Meier method. The location and extent of local failures were transferred to the pretreatment planning computed tomography (CT) for dosimetric analysis. RESULTS: With a median follow-up time of 95 months (range, 16-142 months), 23 local failures were found. The estimated 10-year LC and OS rates were 81.1%and 54.8% respectively. Among the 20 local failures with available diagnostic images, 18(90%) occurred within the 95% isodose lines and were considered in-field failures and 2(10%) were marginal. There was no outside-field failure. CONCLUSIONS: In-field failure was the major pattern of local failure for T4 NPC. IMRT with reduced target volume after IC seems to be feasible. Further researches exploring optimal volume and radiation dose for local advanced NPC in the era of IC are warranted.
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Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa. To develop these comprehensive guidelines for the diagnosis and management of NPC, the Chinese Society of Clinical Oncology (CSCO) arranged a multi-disciplinary team comprising of experts from all sub-specialties of NPC to write, discuss, and revise the guidelines. Based on the findings of evidence-based medicine in China and abroad, domestic experts have iteratively developed these guidelines to provide proper management of NPC. Overall, the guidelines describe the screening, clinical and pathological diagnosis, staging and risk assessment, therapies, and follow-up of NPC, which aim to improve the management of NPC.
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Neoplasias Nasofaríngeas , China , Humanos , Oncologia , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/terapiaRESUMO
PURPOSE: Reirradiation for locally recurrent nasopharyngeal carcinoma (NPC) is challenging because prior radiation dose delivered in the first course is often close to the tolerance limit of surrounding normal structures. A delicate balance between achieving local salvage and minimizing treatment toxicities is needed. However, high-level evidence is lacking because available reports are mostly retrospective studies on small series of patients. Pragmatic consensus guidelines, based on an extensive literature search and the pooling of opinions by leading specialists, will provide a useful reference to assist decision-making for these difficult decisions. METHODS AND MATERIALS: A thorough review of available literature on recurrent NPC was conducted. A set of questions and preliminary draft guideline was circulated to a panel of international specialists with extensive experience in this field for voting on controversial areas and comments. A refined second proposal, based on a summary of the initial voting and different opinions expressed, was recirculated to the whole panel for review and reconsideration. The current guideline was based on majority voting after repeated iteration for final agreement. RESULTS: The initial round of questions showed variations in clinical practice even among the specialists, reflecting the lack of high-quality supporting data and the difficulties in formulating clinical decisions. Through exchange of comments and iterative revisions, recommendations with high-to-moderate agreement were formulated on general treatment strategies and details of reirradiation (including patient selection, targets contouring, dose prescription, and constraints). CONCLUSION: This paper provides useful reference on radical salvage treatment strategies for recurrent NPC and optimization of reirradiation through review of published evidence and consensus building. However, the final decision by the attending clinician must include full consideration of an individual patient's condition, understanding of the delicate balance between risk and benefits, and acceptance of risk of complications.
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Internacionalidade , Carcinoma Nasofaríngeo/radioterapia , Guias de Prática Clínica como Assunto , Radioterapia de Intensidade Modulada , Reirradiação , Intervalo Livre de Doença , Humanos , Dosagem Radioterapêutica , Recidiva , Terapia de SalvaçãoRESUMO
PURPOSE: The aim of this joint guideline is to provide evidence-based recommendations to practicing physicians and other healthcare providers on definitive-intent chemoradiotherapy for patients with stage II-IVA nasopharyngeal carcinoma (NPC). METHODS: The Chinese Society of Clinical Oncology (CSCO) and ASCO convened an expert panel of radiation oncology, medical oncology, surgery, and advocacy representatives. The literature search included systematic reviews, meta-analyses, and randomized controlled trials published from 1990 through 2020. Outcomes of interest included survival, distant and locoregional disease control, and quality of life. Expert panel members used this evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS: The literature search identified 108 relevant studies to inform the evidence base for this guideline. Five overarching clinical questions were addressed, which included subquestions on radiotherapy (RT), chemotherapy sequence, and concurrent, induction, and adjuvant chemotherapy options. RECOMMENDATIONS: Evidence-based recommendations were developed to address aspects of care related to chemotherapy in combination with RT for the definitive-intent treatment of stage II to IVA NPC.Additional information is available at www.asco.org/head-neck-cancer-guidelines.
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Quimiorradioterapia/normas , Oncologia/normas , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/mortalidade , Consenso , Humanos , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/secundário , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias , Qualidade de Vida , Radioterapia (Especialidade)/normas , Resultado do TratamentoRESUMO
PURPOSE: The treatment of nasopharyngeal carcinoma requires high radiation doses. The balance of the risks of local recurrence owing to inadequate tumor coverage versus the potential damage to the adjacent organs at risk (OARs) is of critical importance. With advancements in technology, high target conformality is possible. Nonetheless, to achieve the best possible dose distribution, optimal setting of dose targets and dose prioritization for tumor volumes and various OARs is fundamental. Radiation doses should always be guided by the As Low As Reasonably Practicable principle. There are marked variations in practice. This study aimed to develop a guideline to serve as a global practical reference. METHODS AND MATERIALS: A literature search on dose tolerances and normal-tissue complications after treatment for nasopharyngeal carcinoma was conducted. In addition, published guidelines and protocols on dose prioritization and constraints were reviewed. A text document and preliminary set of variants was circulated to a panel of international experts with publications or extensive experience in the field. An anonymized voting process was conducted to rank the proposed variants. A summary of the initial voting and different opinions expressed by members were then recirculated to the whole panel for review and reconsideration. Based on the comments of the panel, a refined second proposal was recirculated to the same panel. The current guideline was based on majority voting after repeated iteration for final agreement. RESULTS: Variation in opinion among international experts was repeatedly iterated to develop a guideline describing appropriate dose prioritization and constraints. The percentage of final agreement on the recommended parameters and alternative views is shown. The rationale for the recommendations and the limitations of current evidence are discussed. CONCLUSIONS: Through this comprehensive review of available evidence and interactive exchange of vast experience by international experts, a guideline was developed to provide a practical reference for setting dose prioritization and acceptance criteria for tumor volumes and OARs. The final decision on the treatment prescription should be based on the individual clinical situation and the patient's acceptance of optimal balance of risk.
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Cooperação Internacional , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Órgãos em Risco/efeitos da radiação , Radioterapia de Intensidade Modulada , Técnica Delphi , Abordagem GRADE , Humanos , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia , Lesões por Radiação/prevenção & controle , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Carga TumoralRESUMO
BACKGROUND: The aim of this study was to investigate dosimetric factors for predicting acute lymphopenia and the survival of glioma patients with postoperative intensity-modulated radiotherapy (IMRT). METHODS: A total of 148 glioma patients were reviewed. Acute lymphopenia was defined as a peripheral lymphocyte count (PLC) lower than 1.0 × 109 /L during radiotherapy with a normal level at pretreatment. PLCs with the corresponding dates and dose volume histogram parameters were collected. Univariate and multivariate Cox regression analyses were constructed to assess the significance of risk factors associated with lymphopenia and overall survival (OS). RESULTS: Sixty-nine (46.6%) patients developed lymphopenia during radiotherapy. Multivariate analyses revealed that the risk increased with the maximal dose of the hypothalamus (HT Dmax) ≥56 Gy (58.9% vs 28.5%, P = 0.002), minimal dose of the whole brain (WB Dmin) ≥2 Gy (54.3% vs 33.9%, P = 0.006), or mean dose of the WB (WB Dmean) ≥34 Gy (56.0% vs 37.0%, P = 0.022). Patients with older age, high-grade glioma, development of lymphopenia, high HT Dmax, WB Dmin, and WB Dmean had significantly inferior OS in the multivariate analyses. CONCLUSIONS: HT Dmax, WB Dmin, and WB Dmean are promising indicators of lymphopenia and the survival of glioma patients undergoing postoperative IMRT. The necessity and feasibility of dosimetric constraints for HT and WB is warranted with further investigation.
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Encéfalo/efeitos da radiação , Glioma/complicações , Glioma/mortalidade , Hipotálamo/efeitos da radiação , Linfopenia/etiologia , Linfopenia/mortalidade , Radiometria , Idoso , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/terapia , Feminino , Glioma/diagnóstico , Glioma/terapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Radioterapia/efeitos adversos , Dosagem Radioterapêutica , Estudos RetrospectivosRESUMO
BACKGROUND: In patients with T4 nasopharyngeal carcinoma (NPC), death may occur prior to the occurrence of temporal lobe injury (TLI). Because such competing risk death precludes the occurrence of TLI and thus the competing risk analysis should be applied to TLI research. The aim was to investigate the incidence and predictive factors of TLI after intensity-modulated radiotherapy (IMRT) among T4 NPC patients. METHODS: From March 2008 to December 2014, T4 NPC patients treated with full-course radical IMRT at our center were reviewed retrospectively. A nested case-control study was designed for this cohort of patients. The cases were patients with TLI diagnosed by MRI during the follow-up period, and the controls were patients without TLI after IMRT matched 1:1 to each case by gender, age at diagnosis, intercranial involvement, and follow-up time. The end point was time to TLI or death without prior TLI. We analyzed the cumulative incidence function (CIF) and performed a competing risk regression model to identify the predictors of TLI. RESULTS: With a median follow-up of 40.1 months, 63 patients (63/506, 12.5%) developed TLI as diagnosed by MRI, and 136 deaths occurred during the period. The cumulative incidence of TLI at 5 years was 13.2%, while 26.7% died without prior TLI. The univariate analysis showed that all selected dosimetric parameters were associated with the occurrence of TLI. On multivariate analysis, D1cc and V20 remained statistically significant. Based on the area-under-the-curve (AUC) values, D1cc was considered the most predictive. The patients with D1cc > 71.14 Gy had a 7.920-fold increased risk of TLI compared with those with D1cc ≤71.14 Gy (P < 0.05). Similarly, V20 > 42.22 cc was found to result in a statistically significant higher risk of TLI (subdistribution hazard ratio [sHR] =3.123, P < 0.05). CONCLUSIONS: TL D1cc and V20 were predictive of TLI after IMRT for T4 NPC. They should be considered as first and second priorities of dose constraints of the TL. D1cc ≤71.14 Gy and V20 ≤ 42.22 cc could be useful dose-volume constraints for reducing the occurrence of TLI during IMRT treatment planning without obviously compromising the tumor coverage.
Assuntos
Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Lesões por Radiação/epidemiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Lobo Temporal/efeitos da radiação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Irradiação Craniana/efeitos adversos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/mortalidade , Lesões por Radiação/etiologia , Radiometria , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Adulto JovemRESUMO
To report long-term results of a randomized controlled trial that compared cisplatin/fluorouracil/docetaxel (TPF) induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) with CCRT alone in locoregionally advanced nasopharyngeal carcinoma (NPC). Patients with stage III-IVB (except T3-4 N0) NPC were randomly assigned to receive IC plus CCRT (n = 241) or CCRT alone (n = 239). IC included three cycles of docetaxel (60 mg/m2 d1), cisplatin (60 mg/m2 d1), and fluorouracil (600 mg/m2 /d civ d1-5) every 3 weeks. Patients from both groups received intensity-modulated radiotherapy concurrently with three cycles of 100 mg/m2 cisplatin every 3 weeks. After a median follow-up of 71.5 months, the IC plus CCRT group showed significantly better 5-year failure-free survival (FFS, 77.4% vs. 66.4%, p = 0.019), overall survival (OS, 85.6% vs. 77.7%, p = 0.042), distant failure-free survival (88% vs. 79.8%, p = 0.030), and locoregional failure-free survival (90.7% vs. 83.8%, p = 0.044) compared to the CCRT alone group. Post hoc subgroup analyses revealed that beneficial effects on FFS were primarily observed in patients with N1, stage IVA, pretreatment lactate dehydrogenase ≥170 U/l, or pretreatment plasma Epstein-Barr virus DNA ≥6000 copies/mL. Two nomograms were further developed to predict the potential FFS and OS benefit of TPF IC. The incidence of grade 3 or 4 late toxicities was 8.8% (21/239) in the IC plus CCRT group and 9.2% (22/238) in the CCRT alone group. Long-term follow-up confirmed that TPF IC plus CCRT significantly improved survival in locoregionally advanced NPC with no marked increase in late toxicities and could be an option of treatment for these patients.
Assuntos
Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Adolescente , Adulto , Quimiorradioterapia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nomogramas , Prognóstico , Reprodutibilidade dos Testes , Adulto JovemRESUMO
BACKGROUND: To analyze the prognostic value of the clinicopathological parameters of primary lesions for predicting cervical lymph node metastasis in patients with hypopharyngeal and/or supraglottic carcinoma. METHODS: We enrolled 127 patients with squamous cell carcinomas originating in the hypopharyngeal and/or supraglottic regions. RESULTS: Multivariate analysis identified the tumor depth as an independent predictive factor for lymph node metastasis (odds ratio, 4.959; 95% confidence interval, 2.290-10.739; P < 0.0001) with a predictive value of 0.966. A cutoff value of 4.5 mm was determined. CONCLUSION: The tumor depth of the primary lesion is a potent predictor of cervical lymph node metastasis in hypopharyngeal and supraglottic carcinomas. In cases with clinically negative nodal status, elective neck dissection should be adopted for patients with a tumor depth reaching 4.5 mm. Regular outpatient follow-up is recommended for patients with a tumor depth less than 1.0 mm. Close follow-up or preventative therapy should be considered between 1.0 and 4.5 mm.
Assuntos
Carcinoma/patologia , Neoplasias Hipofaríngeas/patologia , Neoplasias Laríngeas/patologia , Metástase Linfática , Carcinoma/terapia , Feminino , Humanos , Neoplasias Hipofaríngeas/terapia , Neoplasias Laríngeas/terapia , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Esvaziamento Cervical , Prognóstico , Radioterapia Adjuvante , Estudos RetrospectivosRESUMO
PURPOSE: To analyze the potential variables affecting the survival of patients undergoing primary surgery for hypopharyngeal squamous cell carcinoma. PATIENTS AND METHODS: Between August 2007 and December 2016, 93 patients with primary hypopharyngeal squamous cell carcinomas undergoing radical surgery at Fudan University Shanghai Cancer Center were reviewed. The clinicopathological features were analyzed retrospectively. The optimal cutoff values were determined based on the receiver operating characteristic curve analysis. Pearson correlation coefficients were used to assess the correlations between variables. The Kaplan-Meier and Cox proportional hazard methods were used to evaluate the impact of variables on overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). RESULTS: Cox multivariate analysis revealed that a depth of invasion (DOI) ≥ 4.3 mm was correlated with inferior OS (P=0.045), DSS (P=0.046), and DFS (P=0.046). A primary tumor volume (PTV) ≥0.36 mL was related to poor OS (P=0.018), DSS (P=0.026), and DFS (P=0.036). A lymph node density (LND) ≥0.07 was also associated with worse OS (P=0.014) and DSS (P=0.045). Moreover, additional prognostic value was observed in the combined use of PTV and LND. CONCLUSION: The DOI, PTV, and LND obtained from the surgical specimens could provide additional valuable information for prognostic stratification and allowed the more appropriate selection of suitable candidates for more aggressive adjuvant therapy.