Diagnostic performance of response assessment FDG-PET/CT in patients with head and neck squamous cell carcinoma treated with high-precision definitive (chemo)radiation

doi:10.1016/j.radonc.2010.04.028

Radiotherapy and Oncology

Volume 97, Issue 2, November 2010, Pages 194-199

https://doi.org/10.1016/j.radonc.2010.04.028 Get rights and content

Abstract

Purpose

To prospectively assess diagnostic performance of response assessment fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in patients with HNSCC treated with high-precision definitive (chemo)radiation.

Methods

Fifty-seven patients treated on a prospective clinical trial having post-treatment response assessment FDG-PET/CT scans were included. Clinico-pathologic findings and follow-up information was considered as reference standard.

Results

First response assessment FDG-PET/CT was done at a median of 9 weeks (inter-quartile range 8–10 weeks) from completion of treatment. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of first response assessment FDG-PET/CT for identifying residual disease at primary site was 50%, 91.8%, 50%, 91.8%, and 86%. The corresponding figures for the neck were 62.5%, 98%, 83.3%, 94.1%, and 93%. With a median follow-up of 26 months (range 7–45 months), the 3-year loco-regional control (83.9% vs 58.3%, p = 0.001) and overall survival (68.8% vs 58.3%, p = 0.063) was significantly better in patients with negative response assessment scans.

Conclusion

The overall diagnostic accuracy of response assessment FDG-PET/CT is good, but its sensitivity and PPV is somewhat low, particularly for primary site. A negative response assessment FDG-PET/CT scan is highly suggestive of absence of viable disease that could be used to guide decision-making.

Section snippets

Materials and methods

Sixty-two, previously untreated patients with squamous cell carcinoma of the oropharynx, larynx, or hypopharynx with American Joint Committee on Cancer (AJCC) stage T1–T3, N0-2b, M0 (excepting T1 glottic larynx) were accrued between December 2005 and April 2008 on an institutional review board approved prospective phase II randomized controlled trial comparing 3D-CRT with IMRT as definitive treatment. Conformal radiotherapy was delivered in 2–3 sequential phases to a total tumor dose of 70 Gy in

Results

Two patients refused any treatment after randomization, two others completed planned treatment but refused any response assessment imaging, while one patient died within 4 weeks of completion of (chemo)radiation, leaving 57 patients who underwent response assessment FDG-PET/CT scans and constitute the dataset of this analysis. The median age of the study cohort was 54 years (range 33–65 years). The patient and the disease characteristics for the cohort are summarized in Table 1. The median SUV_max

Discussion

The primary objective of this correlative study was to evaluate the diagnostic performance of FDG-PET/CT for response assessment at the primary site and the neck nodes for early to moderately advanced squamous cell cancers of the head and neck treated with high-precision definitive (chemo)radiation. In recent times, there have been numerous reports in the indexed medical literature substantiating the clinical utility of FDG-PET and/or FDG-PET/CT in the diagnosis, staging, planning, response

Conclusions

FDG-PET/CT can help identify residual/recurrent viable tumor following definitive (chemo)radiation in HNSCC. The metabolic-anatomic information from co-registered FDG-PET/CT provides an accurate assessment of treatment response. The overall diagnostic accuracy of response assessment FDG-PET/CT is good, but its sensitivity and PPV is somewhat low in this setting, particularly for the primary site. Its NPV remains very high and a negative response assessment scan after definitive (chemo)radiation

Conflict of interest

None of the authors have any conflict of interest to declare.

Role of funding source: FDG-PET/CT scans on the study were partly supported by a philanthropic grant from an individual donor (name withheld on donor request), who had no role in the study design, conduct, collection, analysis, and interpretation of data, which was done by the authors themselves.

Presentation: Presented in part at the 2nd American Society of Therapeutic Radiology & Oncology (ASTRO) Translational Research Meeting,

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The management of the neck following radiotherapy (RT) with or without chemotherapy [(chemo)RT] for node positive (N+) mucosal head and neck cancer varies amongst institutions [1]. Institutions that direct management of the neck based on treatment response assessment with a re-staging 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scan have largely based this approach on the predictive values (PV) of this scan, in particular the high negative PV [2–4]. This approach has gained support from randomized controlled trial data, which showed non-inferior outcomes compared to planned neck dissection [5].
To assess the utility of a repeat positron emission tomography/computed tomography (PET/CT) instead of immediate neck dissection (ND) for incomplete nodal response (IR) in Human Papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPC) following chemoradiotherapy/radiotherapy [(chemo)RT].
Patients with non-distant metastatic, node positive (N+) disease treated between Jan/2005 to Jan/2016, achieved complete response at the primary with no distant relapse on a 12-week re-staging PET/CT were evaluated. Patients underwent surveillance after complete nodal response (CR). Patients with IR underwent repeat PET/CT at 16 weeks to direct neck management. Primary endpoints were CR conversion rate and subsequent regional failure following a 16-week PET/CT directed ND. Secondary endpoints were predictive values (PV) of the 12- and 16-week PET/CT for residual nodal disease, predictors for requiring the 16-week PET/CT, 5 year regional, locoregional failure free survival (FFS) and overall survival (OS).
235 patients were evaluated. Median follow up was 56 (range 19–60) months. 41 patients underwent 16-week re-staging PET/CT, 29 (71%) converted to CR. No subsequent regional failures occurred following a 16-week PET/CT directed ND. Positive and negative PV of the 12- and 16-week PET/CT for residual nodal disease was 12% & 98%, and 33% & 97%, respectively. N-category (AJCC/UICC 7th edition) predicted for requiring a 16-week PET/CT on univariate analysis (P-value 0.02). 5 year regional, locoregional FFS and OS was 95.8%, 93.4% and 90.8%, respectively.
For N+ HPV-associated OPC achieving IR on the 12-week re-staging PET/CT following (chemo)RT, a repeat 16-week PET/CT can spare patients from unnecessary surgery.
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Complementary imaging techniques that round out the clinical examination are fundamentally important in the work-up of patients with oral squamous cell carcinoma (OSCC). Above all, exact determination of primary tumour extent, metastatic spread, and treatment response highly depend on accurate imaging methods. Despite a multitude of recently published reviews, there is still an ongoing debate regarding the best imaging method. In order to update the current literature with the latest evidence, a systematic literature search via Pubmed was performed. In total, 56 studies were enrolled, 4170 patients were analysed, and twenty different imaging methods were evaluated referring to their sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV).
In summary, CT (computed tomography) and MRI (magnetic resonance imaging) currently remain the gold standard for evaluating extension of the primary tumour site. No additional evidence could be obtained for functional imaging methods displaying metastatic spread in the cervical lymph nodes, but was found for distant metastases. Furthermore, functional imaging seems to be beneficial in evaluating treatment response. There is further evidence in the accuracy of the different imaging methods found in this update that could possibly be implemented into the revision of the current guidelines and obtain a clear and coherent approach in the clinical set-up.
Change of maximum standardized uptake value slope in dynamic triphasic [<sup>18</sup>F]-fluorodeoxyglucose positron emission tomography/computed tomography distinguishes malignancy from postradiation inflammation in head-and-neck squamous cell carcinoma: A prospective trial
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[18F]-Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is a combined metabolic/anatomic imaging modality, which improves diagnostic accuracy and staging in HNSCC patients (2-11). However, its accuracy in assessing treatment response after RT is poorly optimized, with scarce prospective data (12-14). Early detection of persistent and recurrent disease is important for immediate salvage treatment.
To evaluate dynamic [¹⁸F]-fluorodeoxyglucose (FDG) uptake methodology as a post–radiation therapy (RT) response assessment tool, potentially enabling accurate tumor and therapy-related inflammation differentiation, improving the posttherapy value of FDG–positron emission tomography/computed tomography (FDG-PET/CT).
We prospectively enrolled head-and-neck squamous cell carcinoma patients who completed RT, with scheduled 3-month post-RT FDG-PET/CT. Patients underwent our standard whole-body PET/CT scan at 90 minutes, with the addition of head-and-neck PET/CT scans at 60 and 120 minutes. Maximum standardized uptake values (SUV_max) of regions of interest were measured at 60, 90, and 120 minutes. The SUV_max slope between 60 and 120 minutes and change of SUV_max slope before and after 90 minutes were calculated. Data were analyzed by primary site and nodal site disease status using the Cox regression model and Wilcoxon rank sum test. Outcomes were based on pathologic and clinical follow-up.
A total of 84 patients were enrolled, with 79 primary and 43 nodal evaluable sites. Twenty-eight sites were interpreted as positive or equivocal (18 primary, 8 nodal, 2 distant) on 3-month 90-minute FDG-PET/CT. Median follow-up was 13.3 months. All measured SUV endpoints predicted recurrence. Change of SUV_max slope after 90 minutes more accurately identified nonrecurrence in positive or equivocal sites than our current standard of SUV_max ≥2.5 (P=.02).
The positive predictive value of post-RT FDG-PET/CT may significantly improve using novel second derivative analysis of dynamic triphasic FDG-PET/CT SUV_max slope, accurately distinguishing tumor from inflammation on positive and equivocal scans.
Long-term results of positron emission tomography-directed management of the neck in node-positive head and neck cancer after organ preservation therapy
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The current study presents the long-term results from a study designed to evaluate a restaging positron emission tomography (PET) directed policy whereby neck dissections were omitted in all node positive head and neck squamous cell carcinoma (N + HNSCC) patients with PET-negative lymph nodes after definitive radiotherapy (RT), with or without chemotherapy.
A post-therapy nodal response assessment with PET and computed tomography (CT) was performed in patients who achieved a complete response at the primary site after definitive radiotherapy. Patients with PET-negative lymph nodes were observed regardless of residual CT abnormalities.
One hundred and twelve patients, the majority of whom (83 patients, 74%) had oropharyngeal primaries, were treated on protocol. Median follow-up was 62 months. Negative and positive predictive values for the restaging PET was 97.1% and 77.8% respectively, with only one patient who was PET-negative after treatment experiencing an isolated nodal relapse.
PET-guided management of the neck following organ preservation therapy effectively spares neck dissections in patients with N + HNSCC without compromising isolated nodal control or overall survival.
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The fusion imaging modality of positron-emission tomography-computed tomography (PET-CT) has emerged as an important modality in the management of recurrent head and neck tumors. The aims of this study were to assess the role of PET-CT in the detection of recurrence in treated head and neck squamous cell carcinoma (HNSCC) and compare neck PET-CT and contrast-enhanced computed tomography (CECT) in the detection of locoregional recurrence with histopathologic correlation.
The study design was prospective and the study consisted of patients with treated HNSCC referred to the Department of Radiology at Rajiv Gandhi Cancer Institute and Research Center for follow-up or for clinical suspicion of recurrence. PET-CT and CECT neck images were obtained to detect recurrence based on clinical suspicion or as routine follow-up. Comparison of CECT and PET-CT results was performed using receiver operating characteristics (ROC) curves for the detection of locoregional recurrence with histopathologic correlation.
Fifty-eight patients with treated HNSCC underwent neck PET-CT and CECT to detect recurrence based on clinical suspicion or as routine follow-up. The sensitivity and specificity of PET-CT for the detection of locoregional recurrence were 100% and 97.37%, which were considerably higher than 85% and 71.05% when using CECT. The ROC curve and its analysis showed that regional PET-CT is superior to neck CECT in the detection of locoregional recurrence (P = .02). When considering recurrence at the metastatic site, the sensitivity and specificity of PET-CT were 100% and 97.06%. PET-CT also detected second primary tumors in 2 patients.
PET-CT not only is superior to conventional CECT in the detection of recurrence at locoregional and lymph node sites, but also plays a role in the restaging of recurrent tumors and the detection of distant metastases and second primary tumors. PET-CT, if included in routine post-treatment HNSCC follow-up or in a protocol for suspected recurrence, may have a major impact on the management of patients after treatment of HNSCC.

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PET imaging in head and neckDiagnostic performance of response assessment FDG-PET/CT in patients with head and neck squamous cell carcinoma treated with high-precision definitive (chemo)radiation

Abstract

Purpose

Methods

Results

Conclusion

Section snippets

Materials and methods

Results

Discussion

Conclusions

Conflict of interest

Lancet

Radiother Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

PET Clin

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Eur J Radiol

Eur J Radiol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Oral Oncol

Int J Radiat Oncol Biol Phys

Acta Otorrinolaringol Esp

Auris Nasus Larynx

Parotid gland sparing IMRT for head and neck cancer improves xerostomia related quality of life

Radiat Oncol

Head and neck cancer: how imaging predicts treatment outcome

Cancer Imaging

PET imaging in head and neck
Diagnostic performance of response assessment FDG-PET/CT in patients with head and neck squamous cell carcinoma treated with high-precision definitive (chemo)radiation