Cost-effectiveness analysis of PET-CT-guided management for locally advanced head and neck cancer

doi:10.1016/j.ejca.2017.07.054

European Journal of Cancer

Volume 85, November 2017, Pages 6-14

https://doi.org/10.1016/j.ejca.2017.07.054 Get rights and content

Highlights

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A Markov model was used to assess the impact of positron-emission tomography–computed tomography (PET-CT)-guided management for head and neck cancer.
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PET-CT was found to be cost-effective over a lifetime horizon from a United Kingdom secondary care perspective.
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PET-CT is expected to reduce per-patient secondary care lifetime costs by £1485.
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PET-CT is expected to increase per-patient quality-adjusted life years (QALYs) by +0.13 QALYs.

Abstract

Background

A recent large United Kingdom (UK) clinical trial demonstrated that positron-emission tomography–computed tomography (PET-CT)-guided administration of neck dissection (ND) in patients with advanced head and neck cancer after primary chemo-radiotherapy treatment produces similar survival outcomes to planned ND (standard care) and is cost-effective over a short-term horizon. Further assessment of long-term outcomes is required to inform a robust adoption decision. Here we present results of a lifetime cost-effectiveness analysis of PET-CT-guided management from a UK secondary care perspective.

Methods

Initial 6-month cost and health outcomes were derived from trial data; subsequent incidence of recurrence and mortality was simulated using a de novo Markov model. Health benefit was measured in quality-adjusted life years (QALYs) and costs reported in 2015 British pounds. Model parameters were derived from trial data and published literature. Sensitivity analyses were conducted to assess the impact of uncertainty and broader National Health Service (NHS) and personal social services (PSS) costs on the results.

Results

PET-CT management produced an average per-person lifetime cost saving of £1485 and an additional 0.13 QALYs. At a £20,000 willingness-to-pay per additional QALY threshold, there was a 75% probability that PET-CT was cost-effective, and the results remained cost-effective over the majority of sensitivity analyses. When adopting a broader NHS and PSS perspective, PET-CT management produced an average saving of £700 and had an 81% probability of being cost-effective.

Conclusions

This analysis indicates that PET-CT-guided management is cost-effective in the long-term and supports the case for wide-scale adoption.

Introduction

Chemo-radiotherapy (CRT) has become a mainstay of primary treatment for many patients with squamous-cell carcinoma of the head and neck. However, for patients with advanced nodal disease (stage N2 or N3), there remains variation in subsequent treatment management. Evidence of persistent disease in nodes after neck dissection (ND) in up to 40% of patients, combined with some evidence of a survival advantage resulting from surgery, has led to many centres maintaining ND as the preferred treatment strategy [1], [2], [3]. However, in the 30–45% of patients exhibiting complete response on imaging after CRT, less than 10% go on to experience disease recurrence [4], [5]; combined with recent improvements in imaging technology, this has led to the sporadic adoption of image-guided treatment strategies in some countries as a means of sparing low-risk patients from the morbidity and expense of unnecessary surgery.

A recent United Kingdom (UK) clinical trial (PET-Neck) was conducted to assess the clinical utility and cost-effectiveness of a combined 18F-fluorodeoxyglucose positron-emission tomography and computed tomography (PET-CT)-guided management for patients with advanced squamous-cell carcinoma [6]. The study found that over the trial 2-year follow-up period, overall survival (OS) was similar among patients in the PET-CT arm compared to those who underwent planned ND (84.9% versus 81.5%, respectively). In addition, mainly as a result of fewer operations (54 versus 221), the intervention was associated with a 2-year cost-saving of £1492. Combined with a small increase (+0.08) in quality-adjusted life years (QALYs), PET-CT-guided management was found to be cost-effective over the 2-year trial horizon.

Uncertainty remains over the long-term cost-effectiveness of image-guided management. Initial cost-savings associated with PET-CT (largely attributable to the lower procedural cost compared to ND; currently £649 versus £3548, respectively in the UK [7]) may not translate into long-term cost-savings if surgery is merely delayed or if the rate of late-stage recurrence events requiring more aggressive treatments is increased. Wide-scale adoption of new and potentially expensive technologies requires robust evidence on both long-term clinical effectiveness and cost-effectiveness, and local decision makers need to have a clear idea of financial implications. Full consideration of the downstream cost consequences of PET-CT, as well as the impact on patient mortality and quality of life, therefore, needs to be addressed.

Here we report results of the PET-Neck study lifetime cost-effectiveness analysis that, together with previously published clinical outcomes [6], provides vital evidence for the viability of a PET-CT-guided management strategy for this patient group.

Section snippets

Clinical trial

The PET-Neck study was a UK pragmatic multi-centre phase III randomised non-inferiority trial (ISRCTN 13735240). Full details of the trial have been previously published [6]. Briefly, between October 2007 and August 2012, 564 adult patients with head and neck (including oropharyngeal, laryngeal, oral, hypopharyngeal or occult) squamous-cell carcinoma with nodal stage N2 or N3 and no distant metastasis (stage M0) disease were recruited across 43 UK National Health Service (NHS) hospitals.

Results

PET-CT-guided management was associated with a per-patient lifetime NHS secondary care cost-saving of £1485 (i.e. $2133) (95% confidence interval [CI]: −2815 to 159) and a health gain of 0.13 (95% CI: −0.49 to 0.79) QALYs compared to planned ND (see Table 2: lifetime cost-effectiveness results and Fig. 2: scatter plot).¹

Discussion

In addition to verifying the effects on survival and recurrence rates, research into long-term health economic implications is critical to determine the overall value of treatment strategies by weighing up both cost and health outcomes at all points along the patient pathway. This evaluation provides the first confirmation that PET-CT-guided management is likely to provide a cost-effective alternative to planned ND within a randomised setting in the longer term and from a UK health care

Conflict of interest statement

None declared.

Role of the funding source

This work was supported by an academic grant from the National Institute for Health Research Health Technology Assessment Programme [06/302/129]. This paper presents independent research commissioned by the National Institute of Health Research (NIHR) under its Health Technology Assessment Programme. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

MESH headings

Positron-emission tomography–computed tomography; Head and neck neoplasms; Technology assessment, Biomedical; Cost-benefit analysis; Models, Economic.

Ethics

Ethical approval for the PET-Neck clinical trial was provided by the Oxfordshire Multi-Research Ethics Committee in May 2007 (Ref No: 07/Q1604/35).

Disclaimer

This paper presents independent research commissioned by the National Institute of Health Research (NIHR) under its Health Technology Assessment Programme. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

Acknowledgements

This work was supported by an academic grant from the National Institute for Health Research Health Technology Assessment Programme [06/302/129].

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Cited by (23)

Cost of Illness of Head and Neck Cancer in Sweden
2024, Value in Health
Head and neck cancer (HNC) is the sixth most common cancer worldwide. The condition and its treatment often lead to marked morbidities and, for some patients, premature death. Inferentially, HNC imposes a significant economic burden on society. This study aims to provide a comprehensive and detailed estimation of the cost of illness of HNC for Sweden in 2019.
This is a prevalence-based cost of illness study. Resource utilization and related costs are quantified using national registry data. A societal perspective is applied, including (1) direct costs for healthcare utilization, (2) costs for informal care from family and friends, and (3) costs for productivity loss due to morbidity and premature death. The human capital approach is used when estimating productivity losses.
The societal cost of HNC for Sweden in 2019 was estimated at €92 million, of which the direct costs, costs for informal care, and costs for productivity loss represented 34%, 2%, and 64%, respectively. Oral cavity cancer was the costliest HNC, followed by oropharyngeal cancer, whereas nasopharyngeal cancer was the costliest per person. The cost of premature mortality comprised 60% of the total cost of productivity loss. Males accounted for 65% of direct costs and 67% of costs for productivity loss.
The societal cost of HNC is substantial and constitutes a considerable burden to Swedish society. The results of the present study may be used by policymakers for planning and allocation of resources. Furthermore, the information may be used for future cost-effectiveness analyses.
The Effects of Human Papillomavirus Status and Treatment on the Positive Predictive Value of Post-radiotherapy <sup>18</sup>F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography in Advanced Head and Neck Squamous Cell Carcinoma
2023, Clinical Oncology
The high negative predictive value of post-chemoradiation (CRT) positron emission tomography-computed tomography (PET-CT) is well established in head and neck squamous cell cancers (HNSCC). The positive predictive value (PPV) remains under scrutiny, with increasing evidence that it is affected by several factors. The aim of this study was to assess the PPV of post-treatment PET-CT for residual nodal disease when stratified by treatment modality and tumour human papillomavirus (HPV) status.
This was a retrospective cohort study in a tertiary oncology centre carried out between January 2013 and December 2019. Patients were radically treated with radiotherapy only/CRT for node-positive HNSCC. PET-CT nodal responses were categorised as complete, equivocal (EQR) or incomplete (ICR), and outcomes extracted from electronic records.
In total, 480 patients were evaluated, all had a minimum potential follow-up of 2 years, with a median of 39.2 months. The PPV of 12-week PET-CT was significantly different between HPV-positive (22.5%) and HPV-unrelated (52.7%) disease, P < 0.001. It was also significantly different between the CRT (24.8%) and radiotherapy-only (51.1%) groups, P = 0.001. The PPV of an EQR was significantly less than an ICR, irrespective of HPV status and primary treatment modality. In HPV-positive disease, the PPV of an EQR was 9.0% for the CRT group compared with 21.4% for radiotherapy only, P = 0.278. The PPV in those who achieved an ICR was 34.2% in the CRT group, significantly lower than 70.0% in the radiotherapy-only group, P = 0.03.
The PPV of 12-week PET-CT is significantly lower for HPV-positive compared with HPV-unrelated HNSCC. It is poorer in patients with HPV-positive disease treated with CRT compared with radiotherapy alone.
PET/CT and PET/MRI Evaluation of Post-treatment Head and Neck
2023, Seminars in Roentgenology
Positron Emission Tomography-Computed Tomography Surveillance after (Chemo)Radiotherapy in Advanced Head and Neck Squamous Cell Cancer: Beyond the PET-NECK Protocol
2020, Clinical Oncology
Citation Excerpt :
The PET-NECK study [11] showed the validity of an imaging-based surveillance approach with neck dissections only carried out in patients where there was concern about residual disease after (chemo)radiotherapy. 18-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) scanning 12 weeks after radiotherapy for HNSCC compared with planned neck dissections resulted in a reduction in the number of neck dissections carried out (54 versus 221), with non-inferior survival (2-year overall survival rate: 84.9% and 81.5%, respectively) [11], and was more cost-effective [12]. Thus, PET-CT surveillance after radiotherapy for those with N2–3 disease is now routine practice.
To evaluate the implementation of 18-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) surveillance after (chemo)radiotherapy, to compare outcomes for those who achieved a complete (CR), equivocal (EQR) and incomplete (ICR) nodal response on 12-week PET-CT according to their human papillomavirus (HPV) status, and to assess the safety of ongoing surveillance beyond 12 weeks in the HPV-positive EQR group.
All patients with node-positive head and neck squamous cell carcinoma (HNSCC) treated with (chemo)radiotherapy between January 2013 and September 2017 were identified. PET-CT responses were classified as CR, ICR or EQR. Patient outcomes were obtained from electronic records.
In total, 236 patients with a minimum of 2 years of follow-up were identified. The mean age was 59 years; 79.3% had N2 disease; 77.1% of patients had oropharyngeal cancer and 10.1% had squamous cell carcinoma of unknown primary, of whom 82.0% (169) were HPV positive; 78.0% received chemoradiotherapy. The median time from the end of radiotherapy to PET-CT was 91 days. Of the HPV-related HNSCC, 60.4% achieved CR, 29.0% EQR and 10.6% ICR. With a median follow-up of 41.7 months, there was no difference in survival between patients with HPV-related HNSCC achieving CR and EQR (median overall survival not reached for both, P = 0.67) despite the omission of immediate neck dissection in 98.0% of the EQR group.
Patients with HPV-positive HNSCC who have achieved EQR have comparable survival outcomes to those who achieved a CR despite the omission of immediate neck dissections; this shows the safety of ongoing surveillance beyond 12 weeks in this group of patients.
Unilateral or bilateral irradiation in cervical lymph node metastases of unknown primary? A retrospective cohort study
2019, European Journal of Cancer
Citation Excerpt :
Head and neck cancer of unknown primary (CUP) represents 1%–4% of head and neck tumours [1,2]. Their diagnostic workup includes fine-needle aspiration (FNA) of the node(s), positron-emission tomography–computed tomography (PET-CT) and panendoscopy usually with tonsillectomy and/or mucosectomy [3–11], as well as human papilloma virus (HPV) and Epstein–Barr virus (EBV) testing since the 2017 tumour-node-metastasis (TNM) classification [12]. Neck dissection is used both as a diagnostic and therapeutic modality.
Patients with cervical lymphadenopathy of unknown primary carcinoma (CUP) usually undergo neck dissection and irradiation. There is an ongoing controversy regarding the extent of nodal and mucosal volumes to be irradiated. We assessed outcomes after bilateral or unilateral nodal irradiation.
This retrospective multicentre study included patients with CUP and squamous cellular carcinoma who underwent radiotherapy (RT) between 2000 and 2015.
Of 350 patients, 74.5% had unilateral disease and 25.5% had bilateral disease. Of 297 patients with available data on disease and irradiation sides, 61 (20.5%) patients had unilateral disease and unilateral irradiation, 155 (52.2%), unilateral disease and bilateral irradiation and 81 (27.3%), bilateral disease and bilateral irradiation. Thirty-four (9.7%) and 217 (62.0%) patients received neoadjuvant and/or concomitant chemotherapy, respectively. Median follow-up was 37 months. Three-year local, regional, locoregional failure rates and CUP-specific survival were 5.6%, 11.7%, 15.0% and 84.7%, respectively. In patients with unilateral disease, the 3-year cumulative incidence of regional/local relapse was 7.7%/4.3% after bilateral irradiation versus 16.9%/11.1% after unilateral irradiation (hazard ratio = 0.56/0.61, p = 0.17/0.32). The cumulative incidence of CUP-specific deaths was 9.2% after bilateral irradiation and 15.5% after unilateral irradiation (p = 0.92). In multivariate analysis, mucosal irradiation was associated with better local control, whereas no neck dissection, ≥N2b and interruption of RT for more than 4 days were associated with poorer regional control. Toxicity was higher after bilateral irradiation (p < 0.05). No positron-emission tomography–computed tomography, largest node diameter, ≥N2b, neoadjuvant chemotherapy and interruption of RT were associated with poorer cause-specific survival.
Bilateral nodal irradiation yielded non-significant better nodal and mucosal control rates but was associated with higher rates of severe toxicity.
Pitfalls of post-treatment PET after de-intensified chemoradiotherapy for HPV-associated oropharynx cancer: Secondary analysis of a phase 2 trial
2018, Oral Oncology
Citation Excerpt :
The management of the neck after definitive chemoradiation (CRT) for oropharynx cancer has evolved from planned neck dissection for all patients towards imaging-based surveillance, reserving neck dissection only for those with concern for residual disease. The safety of this approach was recently confirmed by Mehanna et al. in a large randomized trial showing equivalent survival, better quality of life [1], and higher cost-effectiveness [2] in patients with N2 disease randomized to surveillance PET vs. neck dissection. However, there are no consistent standards regarding who to select for neck dissection based on these post-treatment PET scans.
We evaluated patterns of nodal response and positive predictive value (PPV) of 3 month post-treatment PET in patients with HPV-associated oropharyngeal cancer treated on a multi-institutional de-intensification trial.
Eligibility criteria included: (1) T0-3, N0-2c, M0, (2) HPV+/p16+ oropharyngeal squamous cell carcinoma, and (3) ≤10 pack-years smoking or ≤30 pack-years and abstinent ≥5 years. Patients received 60 Gy radiation alone (T0-2, N0-1) or with concurrent weekly cisplatin 30 mg/m² and surveillance PET three months post-radiation. Nodal responses were categorized as complete (CR), equivocal (ER), or incomplete (IR) using both local and central radiographic review. A “true positive” was ER/IR with clinical/radiographic progression or positive pathology.
79 node-positive pts (84% N2) were analyzed. Distribution of nodal CR, ER, and IR was 44 (56%), 27 (34%), and 8 (10%), respectively. 29 (37%) had ER/IR in pre-treatment node-positive neck levels, whereas 14 (18%) had ER/IR in pre-treatment node-negative levels. Of patients with ER/IR, 5 were observed clinically, 19 received repeat imaging, and 11 received either biopsy (1) or neck dissection (10). The PPV was 9% for ER/IR and 13% for IR, with 3 patients found to have persistent disease on neck dissection. There was no difference in nodal relapse rate in patients with nodal CR vs. nodal ER/IR.
Post-treatment PET may not accurately predict the presence of persistent disease in patients with favorable-risk oropharynx cancer. These results support close surveillance rather than surgical evaluation in most favorable-risk patients.

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Original ResearchCost-effectiveness analysis of PET-CT-guided management for locally advanced head and neck cancer

Highlights

Abstract

Background

Methods

Results

Conclusions

Introduction

Section snippets

Clinical trial

Results

Discussion

Conflict of interest statement

Role of the funding source

MESH headings

Ethics

Disclaimer

Acknowledgements

Int J Radiat Oncol Biol Phys

Ann Oncol

Unresectable primary tumor of head and neck: does neck dissection combined with chemoradiotherapy improve survival?

J Craniofac Surg

The role of cervical lymphadenectomy after aggressive concomitant chemoradiotherapy: the feasibility of selective neck dissection

Arch Otolaryngol Head Neck Surg

Intensive chemoradiotherapy as a primary treatment for organ preservation in patients with advanced cancer of the head and neck: efficacy, toxic effects, and limitations

Arch Otolaryngol Head Neck Surg

Postradiotherapy neck dissection for lymph node–positive head and neck cancer: the use of computed tomography to manage the neck

J Clin Oncol

PET-CT surveillance versus neck dissection in advanced head and neck cancer

N Engl J Med

Reference costs 2013–2014

Guide to the methods of technology appraisal 2013

R: a language and environment for statistical computing

Modeling valuations for EuroQol health states

Med Care

Original Research
Cost-effectiveness analysis of PET-CT-guided management for locally advanced head and neck cancer