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      Prognostic Value of Radiological Extranodal Extension Detected by Computed Tomography for Predicting Outcomes in Patients With Locally Advanced Head and Neck Squamous Cell Cancer Treated With Radical Concurrent Chemoradiotherapy

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          Abstract

          Objective

          Extra Nodal Extension (ENE) assessment in locally advanced head and neck cancers (LAHNCC) treated with concurrent chemo radiotherapy (CCRT) is challenging and hence the American Joint Committee on Cancer (AJCC) N staging. We hypothesized that radiology-based ENE (rENE) may directly impact outcomes in LAHNSCC treated with radical CCRT.

          Materials and Methods

          Open-label, investigator-initiated, randomized controlled trial (RCT) (2012–2018), which included LAHNSCC planned for CCRT. Patients were randomized 1:1 to radical radiotherapy (66–70 grays) with concurrent weekly cisplatin (30 mg/m 2) [cisplatin radiation arm (CRT)] or same schedule of CRT with weekly nimotuzumab (200 mg) [nimotuzumab plus CRT (NCRT)]. A total of 536 patients were accrued and 182 were excluded due to the non-availability of Digital Imaging and Communications in Medicine (DICOM) computed tomography (CT) data. A total of 354 patients were analyzed for rENE. Metastatic nodes were evaluated based on five criteria and further classified as rENE as positive/negative based on three-criteria capsule irregularity with fat stranding, fat invasion, and muscle/vessel invasion. We evaluated the association of rENE and disease-free survival (DFS), loco-regional recurrence-free survival (LRRFS), and overall survival (OS).

          Results

          A total of 244 (68.9%) patients had radiologically metastatic nodes (rN), out of which 140 (57.3%) had rENE. Distribution of rENE was balanced in the two study groups CRT or NCRT (p-value 0.412). The median follow-up period was 39 months (ranging from 35.5 to 42.8 months). Complete response (CR) was seen in 204 (57.6%); incomplete response (IR), i.e., partial response plus stable disease (PR + SD), in 126 (35.6%); and progressive disease (PD) in 24 (6.8%). rENE-positive group had poor survival compared to rENE-negative group 3-year OS (46.7% vs. 63.6%), poor DFS (48.8% vs. 87%), and LRRFS (39.9% vs. 60.4%). rENE positive had 1.71 times increased risk of IR than rENE negative. Overall stage, site, clinical metastatic node (cN), response, and rENE were the significant factors for predicting OS, DFS, and LRRFS on univariate analysis. After making adjustment on multivariate analysis, rENE was an independent prognostic factor for DFS and trending to be significant for OS.

          Conclusion

          Pre-treatment rENE is an independent prognostic marker for survival in patients with LAHNSCC treated radically with CCRT that can be used as a potential predictive marker for response to treatment and hence stratify patients into responders vs. non-responders. We propose the mahajan rENE grading system applicable on CT, magnetic resonance imaging, positron emission tomography–contrast-enhanced CT, and ultrasound.

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          Most cited references32

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          Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer.

          We compared concomitant cisplatin and irradiation with radiotherapy alone as adjuvant treatment for stage III or IV head and neck cancer. After undergoing surgery with curative intent, 167 patients were randomly assigned to receive radiotherapy alone (66 Gy over a period of 6 1/2 weeks) and 167 to receive the same radiotherapy regimen combined with 100 mg of cisplatin per square meter of body-surface area on days 1, 22, and 43 of the radiotherapy regimen. After a median follow-up of 60 months, the rate of progression-free survival was significantly higher in the combined-therapy group than in the group given radiotherapy alone (P=0.04 by the log-rank test; hazard ratio for disease progression, 0.75; 95 percent confidence interval, 0.56 to 0.99), with 5-year Kaplan-Meier estimates of progression-free survival of 47 percent and 36 percent, respectively. The overall survival rate was also significantly higher in the combined-therapy group than in the radiotherapy group (P=0.02 by the log-rank test; hazard ratio for death, 0.70; 95 percent confidence interval, 0.52 to 0.95), with five-year Kaplan-Meier estimates of overall survival of 53 percent and 40 percent, respectively. The cumulative incidence of local or regional relapses was significantly lower in the combined-therapy group (P=0.007). The estimated five-year cumulative incidence of local or regional relapses (considering death from other causes as a competing risk) was 31 percent after radiotherapy and 18 percent after combined therapy. Severe (grade 3 or higher) adverse effects were more frequent after combined therapy (41 percent) than after radiotherapy (21 percent, P=0.001); the types of severe mucosal adverse effects were similar in the two groups, as was the incidence of late adverse effects. Postoperative concurrent administration of high-dose cisplatin with radiotherapy is more efficacious than radiotherapy alone in patients with locally advanced head and neck cancer and does not cause an undue number of late complications. Copyright 2004 Massachusetts Medical Society
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            Current concepts in management of oral cancer--surgery.

            Oral cancer is the sixth most common cancer worldwide, with a high prevalence in South Asia. Tobacco and alcohol consumption remain the most dominant etiologic factors, however HPV has been recently implicated in oral cancer. Surgery is the most well established mode of initial definitive treatment for a majority of oral cancers. The factors that affect choice of treatment are related to the tumor and the patient. Primary site, location, size, proximity to bone, and depth of infiltration are factors which influence a particular surgical approach. Tumors that approach or involve the mandible require specific understanding of the mechanism of bone involvement. This facilitates the employment of mandible sparing approaches such as marginal mandibulectomy and mandibulotomy. Reconstruction of major surgical defects in the oral cavity requires use of a free flap. The radial forearm free flap provides excellent soft tissue and lining for soft tissue defects in the oral cavity. The fibula free flap remains the choice for mandibular reconstruction. Over the course of the past thirty years there has been improvement in the overall survival of patients with oral carcinoma largely due to the improved understanding of the biology of local progression, early identification and treatment of metastatic lymph nodes in the neck, and employment of adjuvant post-operative radiotherapy or chemoradiotherapy. The role of surgery in primary squamous cell carcinomas in other sites in the head and neck has evolved with integration of multidisciplinary treatment approaches employing chemotherapy and radiotherapy either sequentially or concurrently. Thus, larynx preservation with concurrent chemoradiotherapy has become the standard of care for locally advanced carcinomas of the larynx or pharynx requiring total laryngectomy. On the other hand, for early staged tumors of the larynx and pharynx, transoral laser microsurgery has become an effective means of local control of these lesions. Advances in skull base surgery have significantly improved the survivorship of patients with malignant tumors of the paranasal sinuses approaching or involving the skull base. Surgery thus remains the mainstay of management of a majority of neoplasms arising in the head and neck area. Similarly, the role of the surgeon is essential throughout the life history of a patient with a malignant neoplasm in the head and neck area, from initial diagnosis through definitive treatment, post-treatment surveillance, management of complications, rehabilitation of the sequelae of treatment, and finally for palliation of symptoms.
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              Changes in the 8th Edition of the American Joint Committee on Cancer (AJCC) Staging of Head and Neck Cancer: Rationale and Implications

              The objectives of this article are to review the major changes in the staging of head and neck cancers and the rationale for the modifications. Information gathered from various institutional reports lead to a better understanding of the clinical and biological behavior of head and neck tumors, resulting in distinct outcomes, which were used to update the staging system. This article reviews the changes in the staging of head and neck cancers published in the 8 th edition of the AJCC/UICC TNM staging system.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                27 May 2022
                2022
                : 12
                : 814895
                Affiliations
                [1] 1 Department of Radiodiagnosis and Imaging, Tata Memorial Hospital, Homi Bhabha National Institute , Mumbai, India
                [2] 2 Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute , Mumbai, India
                [3] 3 Department of Head and Neck Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute , Mumbai, India
                [4] 4 Department of Radiation Oncology, Tata Memorial Hospital, Homi Bhabha National Institute , Mumbai, India
                [5] 5 Department of Pathology, Tata Memorial Hospital, Homi Bhabha National Institute , Mumbai, India
                Author notes

                Edited by: Avraham Eisbruch, University of Michigan, United States

                Reviewed by: Kee Howe Wong, Royal Marsden NHS Foundation Trust, United Kingdom; Barbara Pichi, Hospital Physiotherapy Institutes (IRCCS), Italy

                *Correspondence: Abhishek Mahajan, abhishek.mahajan@ 123456nhs.net

                This article was submitted to Head and Neck Cancer, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2022.814895
                9202501
                35719994
                169ef384-2db5-4b96-91c3-b4be9b7338f9
                Copyright © 2022 Mahajan, Chand, Agarwal, Patil, Vaish, Noronha, Joshi, Kapoor, Sable, Ahuja, Shukla, Menon, Agarwal, Laskar, D’ Cruz, Chaturvedi, Chaukar, Pai, Pantvaidya, Thiagarajan, Rane and Prabhash

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 14 November 2021
                : 13 April 2022
                Page count
                Figures: 8, Tables: 7, Equations: 0, References: 32, Pages: 14, Words: 5147
                Categories
                Oncology
                Original Research

                Oncology & Radiotherapy
                diagnostic imaging,computed tomography,extranodal extension,survival,neoplasm staging,radiology,oral cancers,squamous cell carcinoma

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