The Role of Computed Tomography in the Management of the Neck After Chemoradiotherapy in Patients With Head-and-Neck Cancer

doi:10.1016/j.ijrobp.2010.11.066

International Journal of Radiation OncologyBiologyPhysics

Volume 82, Issue 2, 1 February 2012, Pages 567-573

https://doi.org/10.1016/j.ijrobp.2010.11.066 Get rights and content

Purpose

The aim of this study was to describe the outcome in patients with head-and neck-squamous cell carcinoma (HNSCC) followed up without neck dissection (ND) after concomitant chemoradiotherapy (CRT) based on computed tomography (CT) response. The second objective was to establish CT characteristics that can predict which patients can safely avoid ND.

Methods and Materials

Between 1998 and 2007, 369 patients with node-positive HNSCC were treated with primary CRT at our institution. After a clinical and a radiologic evaluation based on CT done 6 to 8 weeks after CRT, patients were labeled with a complete neck response (CR) or with a partial neck response (PR).

Results

The median follow-up was 44 months. The number of patients presenting with N3, N2, or N1 disease were 54 (15%), 268 (72%), and 47 (13%), respectively. After CRT, 263 (71%) patients reached a CR, and 253 of them did not undergo ND. Ninety-six patients reached a PR and underwent ND. Of those, 34 (35%) had residual disease on pathologic evaluation. A regression of the diameter of ≥80% and a residual largest diameter of 15 mm of nodes had negative pathologic predictive values of 100% and 86%, respectively. The 3-year regional control and survival rates were not different between patients with CR who had no ND and patients with PR followed by ND.

Conclusion

Node-positive patients presenting a CR as determined by CT evaluation 6 to 8 weeks after CRT had a low rate of regional recurrence without ND. This study also suggests that lymph node residual size and percentage of regression on CT after CRT may be useful criteria to guide clinical decisions regarding neck surgery. Those results can help diminish the number of ND procedures with negative results and their associated surgical complications.

Introduction

Concurrent chemotherapy and radiotherapy (CRT) has become the standard of care for most cases of locally advanced head-and-neck squamous cell carcinoma (HNSCC) (1). Controversies remain concerning the role of surgery for the management of the neck with bulky lymph node involvement 2, 3, 4. Patients with a partial regional response after CRT should undergo neck dissection (ND). However, there is no consensus on the treatment of patients with a complete regional response after treatment, and we are unaware of any well-designed randomized trials available. CRT is associated with a high rate of clinical and pathologic (CR), with a low rate of relapse in the neck (5). Thus, systematic ND may expose patients to unwarranted complications with little benefit.

A critical issue in the management of the neck is the absence of universally acknowledged criteria to determine which patients can safely avoid ND. Although there are emerging data on the use of physiologic imaging modality, such as positron emission tomography (PET) 6, 7, 8, data are sparse and conflicting on the role of computed tomography (CT) scan after RT 9, 10, 11 or CRT 12, 13, 14, 15.

At the Centre hospitalier de l’Université de Montréal (CHUM), the policy is to perform a ND in patients receiving CRT only if there is demonstration of residual disease by clinical or radiologic findings. The purpose of this study was to describe the outcome in patients who are followed up without ND based on posttreatment CT response. The second objective was to establish CT characteristics that predict which patients can safely avoid ND.

Section snippets

Study design

In this single-institution retrospective study, the files of all consecutive patients receiving CRT between January 1998 and December 2007 for HNSCC were reviewed under institutional board approval. Inclusion criteria were as follows: (1) Stage III or IVA–B according to the staging criteria in the 6th edition of the American Joint Committee on Cancer; (2) oropharynx, larynx, hypopharynx, oral cavity, or unknown primary; (3) presence of cervical lymph node metastasis (levels I–V); (4)

Characteristics of patients and treatments

Table 1 summarizes the demographics, clinical characteristics, and treatment characteristics of patients included in this study. The mean age at diagnosis was 57 years. The majority of patients had oropharyngeal cancer and Stage IV disease. Twenty-nine percent of patients underwent ND, and 55% of them underwent selective ND.

Initial responses to CRT

The results from 384 consecutive patients treated for locally advanced HNSCC were reviewed (Figure). Given that the goal was to evaluate the management of the neck, we

Discussion

Management of the neck after CRT of initially bulky nodal disease is controversial 2, 3, 4. Few studies have directly compared the outcome in patients who had either planned ND or observation after CR. Some centers recommend planned ND for all patients with N2 and/or N3 disease because of suspected inferior neck control and/or survival with observation 18, 19, 20, 21, 22. It is also argued that such conduct is necessary because of the difficulty in evaluating response and residual neck disease

Conclusion

It is safe to observe node-positive patients with evidence of CR as determined by CT evaluation 6 to 8 weeks after CRT because that population has a low rate of regional recurrence. This study also suggests that lymph node residual size and percentage of regression on CT after CRT may be useful criteria to guide clinical decisions regarding neck surgery. When necessary, selective ND is safe and is not associated with increased regional recurrence. Those results can help diminish the number of

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Cited by (37)

PERCIST and Hopkins criteria and PET/CT metabolic parameters as prognostic factors in squamous head and neck cancer
2023, Revista Espanola de Medicina Nuclear e Imagen Molecular
Valorar la utilidad clínica de los criterios PERCIST, Hopkins y de los cambios en los parámetros cuantitativos de la PET/TC con [¹⁸F]FDG como factores pronósticos para la supervivencia libre de progresión (SLP) y la supervivencia cáncer específica (SCE) en pacientes con cáncer escamoso de cabeza y cuello tratados mediante quimiorradioterapia.
Se valoraron retrospectivamente 40 pacientes (34 hombres) diagnosticados de cáncer escamoso de cabeza y cuello durante un intervalo de 8 años. Se utilizaron los criterios PERCIST y Hopkins para determinar la respuesta al tratamiento. Así mismo, se cuantificaron las variaciones de los parámetros metabólicos SUV máximo (ΔSUVmax), volumen metabólico tumoral (ΔMTV) y glicólisis tumoral total (ΔTLG) entre los estudios PET/TC pre- y postratamiento. El modelo de regresión de Cox, las curvas ROC y el método de Kaplan-Meier se aplicaron para el análisis de factores pronósticos y curvas de supervivencia.
El seguimiento medio fue de 39,4 meses produciéndose 24 recidivas-progresiones y 22 muertes. Tanto los criterios PERCIST y Hopkins como los tres parámetros metabólicos fueron factores predictivos en análisis univariante y solo el ΔSUVmax en el multivariante. El análisis de supervivencia mostró curvas de SLP y SCE significativamente diferentes para los cinco parámetros considerados.
La aplicación de los criterios PERCIST y Hopkins, así como los ΔSUVmax, ΔMTV y ΔTLG de los estudios PET/TC demostraron ser factores pronósticos para la supervivencia en pacientes de nuestro entorno tratados por cáncer de cabeza y cuello. Los resultados podrían ayudar a personalizar el tratamiento.
To assess the clinical utility of PERCIST and Hopkins criteria and changes in [¹⁸F]FDG PET/CT quantitative parameters as prognostic factors for progression-free survival (PFS) and cancer-specific survival (CSS) in patients with head and neck squamous cell carcinoma treated by chemoradiotherapy.
Forty patients (34 men) diagnosed with head and neck squamous cell carcinoma were retrospectively assessed over an interval of 8 years. PERCIST and Hopkins criteria were used to assess response to treatment. Variations in the metabolic parameters maximum SUV (ΔSUVmax), metabolic tumor volume (ΔMTV) and total lesion glycolysis (ΔTLG) between pre- and post-treatment PET/CT studies were also determined. Cox regression model, ROC curves and Kaplan-Meier method were used for the analysis of prognostic factors and survival curves.
The average follow-up was 39.4 months, with 24 progressions and 22 deaths. Both PERCIST and Hopkins criteria and the three metabolic parameters were predictive factors in the univariate analysis and only ΔSUVmax in the multivariate analysis. Survival analysis showed statistically significant differences in PFS and CSS curves for the five parameters considered.
Application of PERCIST and Hopkins criteria as well as ΔSUVmax, ΔMTV and ΔTLG from PET/CT studies proved to be prognostic factors for survival in patients in our setting treated for head and neck cancer. The results could help to personalize treatment.
Diffusion tensor imaging in differentiation of residual head and neck squamous cell carcinoma from post-radiation changes
2018, Magnetic Resonance Imaging
Differentiation between residual head and neck squamous cell carcinoma and post-radiation changes is difficult with routine computed tomography and magnetic resonance imaging.
To assess the reliability and reproducibility of mean diffusivity (MD) and fractional anisotropy (FA) parameters of diffusion tensor imaging in differentiation residual head and neck squamous cell carcinoma from post-radiation changes.
A retrospective analysis of diffusion tensor imaging of 43 patients with head and neck squamous cell carcinoma cancer after radiotherapy. The MD and FA of the lesion were calculated by the same reader at two-time points.
There was a significantly lower difference (P = 0.001) in MD of both readings between residual head and neck squamous cell carcinoma (1.48 ± 0.06 and 1.47 ± 0.07 × 10⁻³ mm²/s) and post-radiation changes (1.72 ± 0.08 and 1.71 ± 0.11 × 10⁻³ mm²/s). The FA of residual head and neck squamous cell carcinoma of both readings (0.41 ± 0.09 and 0.42 ± 0.09) shows a significantly higher difference (P = 0.001) than post-radiation changes (0.17 ± 0.04 and 0.16 ± 0.03). There was excellent intra-reader agreement between both readings using MD (K = 0.958) and FA (K = 0.987). The threshold MD and FA used for differentiating the residual from post-radiation changes of both readings was 1.61, 1.65 × 10⁻³ mm²/s and 0.27, 0.25 with an area under the curve of 0.991, 0.934, 0.993 and 0.990 respectively.
MD and FA of diffusion tensor imaging are non-invasive reliable and reproducible parameters that can help in differentiation residual head and neck squamous cell carcinoma from post-radiation changes.
Viable tumor in salvage neck dissections in head and neck cancer: Relation with initial treatment, change of lymph node size and human papillomavirus
2018, Oral Oncology
To identify predictive factors for the presence of viable tumor and outcome in head and neck cancer patients who undergo therapeutic salvage neck dissections.
Retrospective analysis of 76 salvage neck dissections after radiotherapy alone (n = 22), radiotherapy in combination with carboplatin/5-fluorouracil (n = 42) or with cetuximab (n = 12).
Viable tumor was detected in 41% of all neck dissections. Univariate analysis revealed initial treatment with radiotherapy without systemic therapy (OR 6.93, 95%CI: 2.28–21.07, p < .001), increased lymph node size after initial treatment compared to pretreatment CT scan (OR 20.48, 95%CI: 2.46–170.73, p = .005), more extensive neck dissections (OR 8.40, 95%CI: 2.94–23.98, p < .001), and human papillomavirus negative cancer (OR 4.22, 95%CI: 1.10–16.22, p = .036) as predictors of viable tumor. Patients with decreased or stable, but persistently enlarged lymph node size after chemoradiation had a significantly lower chance of viable tumor (OR 0.15, 95%CI: 0.05–0.41, p < .001). Disease-specific 5-year survival was 34% in case of viable tumor, and 78% when no viable tumor was found (p < .001).
Viable tumor in salvage neck dissections is associated with reduced survival. Radiotherapy alone, human papillomavirus negative cancer and increase in lymph node size, are associated with viable tumor in salvage neck dissections. In case of decreased or stable lymph node size after chemoradiation, watchful waiting could be considered.
Multidisciplinary management of head and neck cancer: First expert consensus using Delphi methodology from the Spanish Society for Head and Neck Cancer (part 2)
2017, Oral Oncology
Citation Excerpt :
The first question is when exactly we should assess the response. Classically, the choice of a time frame depended on the optimal timing for neck dissection (ND) in case of residual neck disease (RND), which is considered between 4 and 12 weeks after CRT to allow for resolution of acute effects while preceding late fibrosis [2,3]. For many years, 8 weeks has been taken as the optimal time to perform it, however, since de introduction of PET/CT for the evaluation of response, most authors and international guidelines recommend 12 weeks, to minimize the rate of false positives caused by radiation-induced delayed inflammatory changes [4].
Head and neck cancer is one of the most frequent malignances worldwide. Despite the site-specific multimodality therapy, up to half of the patients will develop recurrence. Treatment selection based on a multidisciplinary tumor board represents the cornerstone of head and neck cancer, as it is essential for achieving the best results, not only in terms of outcome, but also in terms of organ-function preservation and quality of life. Evidence-based international and national clinical practice guidelines for head and neck cancer not always provide answers in terms of decision-making that specialists have to deal with in their daily practice. This is the first Expert Consensus on the Multidisciplinary Approach for Head and Neck Squamous Cell Carcinoma (HNSCC) elaborated by the Spanish Society for Head and Neck Cancer and based on a Delphi methodology. It offers a number of specific recommendations based on the available evidence and the expertise of our specialists to facilitate decision-making of all health-care specialists involved.
Prognostic Value of p16 Status on the Development of a Complete Response in Involved Oropharynx Cancer Neck Nodes After Cisplatin-Based Chemoradiation: A Secondary Analysis of NRG Oncology RTOG 0129
2016, International Journal of Radiation Oncology Biology Physics
Citation Excerpt :
With a proposed different failure pattern of p16-positive OPC, it is unclear whether these patients will develop more distant metastases (31) with longer follow-up. Although this study indicates that the poor prognostic outcome of viable disease in the neck is referable to p16-negative OPC, it also suggests that the accepted good outcome of a pCR (32) may be referable to p16-positive OPC. When evaluated as a whole, the 2-year LRF of patients with a pCR neck dissection was 12%, consistent with historical series in the literature (8).
To determine the relationship between p16 status and the regional response of patients with node-positive oropharynx cancer treated on NRG Oncology RTOG 0129.
Patients with N1-N3 oropharynx cancer and known p16 status who underwent treatment on RTOG 0129 were analyzed. Pathologic complete response (pCR) rates in patients treated with a postchemoradiation neck dissection (with p16-positive or p16-negative cancer) were compared by Fisher exact test. Patients managed expectantly were compared with those treated with a neck dissection.
Ninety-nine (34%) of 292 patients with node-positive oropharynx cancer and known p16 status underwent a posttreatment neck dissection (p16-positive: n=69; p16-negative: n=30). The remaining 193 patients with malignant lymphadenopathy at diagnosis were observed. Neck dissection was performed a median of 70 (range, 17-169) days after completion of chemoradiation. Neither the pretreatment nodal stage (P=.71) nor the postradiation, pre-neck dissection clinical/radiographic neck assessment (P=.42) differed by p16 status. A pCR was more common among p16-positive patients (78%) than p16-negative patients (53%, P=.02) and was associated with a reduced incidence of local–regional failure (hazard ratio 0.33, P=.003). On multivariate analysis of local–regional failure, a test for interaction between pCR and p16 status was not significant (P=.37). One-hundred ninety-three (66%) of 292 of initially node-positive patients were managed without a posttreatment neck dissection. Development of a clinical (cCR) was not significantly influenced by p16-status (P=.42). Observed patients with a clinical nodal CR had disease control outcomes similar to those in patients with a pCR neck dissection.
Patients with p16-positive tumors had significantly higher pCR and locoregional control rates than those with p16-negative tumors.
Influence of dosimetric and clinical criteria on the requirement of artificial nutrition during radiotherapy of head and neck cancer patients
2016, Radiotherapy and Oncology
Citation Excerpt :
None of these investigations had sufficient power to detect potential differences between chemotherapy regimens. As in all other investigations, gender was irrelevant for impaired deglutition [20–24,56,57]. The patient́s age is discussed controversially.
Intensification of radiotherapy and chemotherapy for head-and-neck cancer (HNC) may lead to increased rates of long term dysphagia as a severe side effect. Mucositis and consequent swallowing problems require artificial nutrition in many HNC patients undergoing radiotherapy or chemoradiation. It is unknown, which predict factors for prophylactic PEG tube insertion appear useful.
From an institutional database, 101 patients (72 male, 29 female, mean age 59.5 years) were identified who underwent radiotherapy or chemoradiation for HNC. Primary end point of the investigation was the need for artificial nutrition for more than 4 days during radiotherapy. Dose volume parameters of defined normal tissue structures potentially of relevance for swallowing ability as well as clinical factors were used to develop a predictive model using a binary multiple logistic regression model.
Whereas several dosimetric and clinical factors were significant predictors for the need of artificial nutrition on univariate analysis, on multivariate analysis only three factors remained independently significant: mean dose to the oropharynx + 1 cm circumferential margin, ECOG performance state (0–1 vs. 2–4), and the use of chemotherapy (yes vs. no).
Using a 3 parameter model we could distinguish HNC-patients with different risks for the need of artificial nutrition during radiotherapy. After independent validation, the model could be helpful to decision on prophylactic PEG tube insertion.

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Clinical InvestigationThe Role of Computed Tomography in the Management of the Neck After Chemoradiotherapy in Patients With Head-and-Neck Cancer

Purpose

Methods and Materials

Results

Conclusion

Introduction

Section snippets

Study design

Characteristics of patients and treatments

Initial responses to CRT

Discussion

Conclusion

Lancet

Semin Radiat Oncol

Lancet Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

J Oral Maxillofac Surg

Radiol Clin North Am

Int J Radiat Oncol Biol Phys

Radiother Oncol

Otolaryngol Head Neck Surg

Eur J Radiol

Planned neck dissection for patients with complete response to chemoradiotherapy: A concept approaching obsolescence

Head Neck

Planned neck dissection following chemoradiotherapy for advanced head and neck cancer: Is it necessary for all?

Head Neck

Pathology and FDG PET correlation of residual lymph nodes in head and neck cancer after radiation treatment

Am J Clini Oncol

The role of positron emission tomography scans in the management of the N-positive neck in head and neck squamous cell carcinoma after chemoradiotherapy

Laryngoscope

Clinical utility of 18F-FDG PET/CT in assessing the neck after concurrent chemoradiotherapy for locoregional advanced head and neck cancer

J Nucl Med

Lymph node-positive head and neck cancer treated with definitive radiotherapy

Cancer

Clinical Investigation
The Role of Computed Tomography in the Management of the Neck After Chemoradiotherapy in Patients With Head-and-Neck Cancer