Cost-Effectiveness of Positron Emission Tomography/ Computed ...

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Cost-Effectiveness of Positron Emission Tomography/ Computed Tomography in the Management of Advanced Head and Neck Cancer George Kurien, MD, Jia Hu, BA, Jeffrey Harris, MD, FRCSC, and Hadi Seikaly, MD, FRCSC ABSTRACT Background: Positron emission tomography/computed tomography (PET/CT) is a newer imaging modality that combines whole-body PET using [18F]fluorodeoxyglucose (FDG) and contrasted high-resolution CT. This has the advantage of combining the functional imaging of FDG-PET with the anatomic detail afforded by CT. Objective: To assess the cost-benefit of whole-body PET/CT as a diagnostic tool in head and neck cancer. Methods: A retrospective cohort (American Joint Committee on Cancer III-IVB squamous cell carcinoma in 2003) was reviewed for costs of diagnostic tests, distant metastases, and treatment type. This was compared to a hypothetical cohort of patients using PET/CT as a sole diagnostic tool using the current literature on test characteristics in the detection of distant metastases. The main outcome measure was the cost of the diagnostic workup, and the secondary outcome measure was the cost of the treatment. Results: The cost of the traditional workup was $450 per patient, whereas the cost of PET/CT workup was $722 per patient. The sensitivity of the traditional workup for lung metastases at 12 months was 14.3%. The average cost of curative surgery was $81,290, radiotherapy was $8,224, and chemotherapy was $1,158. In the cohort of 76 patients reviewed, improved PET/CT sensitivity would theoretically detect three more cases of metastatic disease and reduce the total cohort cost of treatment by $198,526 by relegating these patients to palliation. Conclusions: PET/CT is a more expensive test when used alone in the diagnostic workup of head and neck cancer but results in an overall cost savings by reducing the number of futile radical treatments. There is a cost benefit to the use of PET/CT as the diagnostic and staging test for head and neck cancer patients. SOMMAIRE Contexte: La tomographie par e´mission de positons associeé a` la tomodensitome´trie (TEP/TDM) est une nouvelle technique d’imagerie qui allie la TEP du corps entier, reáliseé avec du 18F-fluode´soxyglucose (FDG), a` la TDM a` haute re´solution contrasteé. La TEP/TDM a donc l’avantage d’associer les images fonctionnelles de la TEP avec les images anatomiques prećises de la TDM. Objectif: L’e´tude visait a` e´valuer le rapport couˆts-avantages de la TEP du corps entier associeé a` la TDM comme outil de diagnostic dans les cancers de la teˆte et du cou. Me´thode: Nous avons proce´de´ a` un examen re´trospectif d’une cohorte (American Joint Committee on Cancer, carcinome squameux III-IVB, en 2003) afin d’e´valuer le couˆt des examens de diagnostic, la de´tection des me´tastases e´loigneés, et le type de traitement. Cette cohorte a e´te´ compareé avec une cohorte hypothe´tique dans laquelle la TEP/TDM aurait e´te´ utiliseé comme seul outil de diagnostic, a` partir de la documentation actuelle sur les caracte´ristiques des examens relativement a` la de´tection des me´tastases e´loigneés. Le principal crite`re d’e´valuation e´tait le couˆt de l’e´laboration du diagnostic, et le crite`re secondaire e´tait le couˆt du traitement. Re´sultats: Le couˆt de l’e´laboration courante e´tait de $450 par patient, tandis que le couˆt de l’e´laboration par la TEP/TDM s’e´levait a` $722 par patient. La sensibilite´ de l’e´laboration courante a` l’e´gard des me´tastases pulmonaires, au bout de 12 mois, e´tait de 14.3%. Le couˆt moyen de la chirurgie curative e´tait de $81 290; celui de la radiothe´rapie, de $8224; et celui de la chimiothe´rapie, de $1158. Dans la cohorte de 76 patients soumise a` l’examen, la sensibilite´ ame´lioreé de la TEP/TDM aurait permis, en principe, de de´tecter

George Kurien, Jeffrey Harris, and Hadi Seikaly: Department of Surgery, and Jia Hu: Faculty of Medicine, University of Alberta, Edmonton, AB. Presented at the Canadian Society of Otolaryngology-Head and Neck Surgery 65th Annual Meeting, May 23, 2011, Victoria, BC.

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Address reprint requests to: Hadi Seikaly, MD, FRCSC, Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Alberta, 1E4.34 WC Mackenzie Health Sciences Centre, 8440 112 Street NW, Edmonton, AB T6G 2B7; e-mail: hadi.seikaly@ albertahealthservices.ca.

DOI 10.2310/7070.2011.110092 # 2011 The Canadian Society of Otolaryngology-Head & Neck Surgery

Journal of Otolaryngology-Head & Neck Surgery, Vol 40, No 6 (December), 2011: pp 468–472

Kurien et al, Cost-Effectiveness of PET/CT in Head and Neck Cancer

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trois cas supple´mentaires d’atteinte me´tastatique et de re´duire le couˆt total des traitements de $198 526 par le passage des patients touche´s aux soins palliatifs. Conclusions: Utiliseé seule dans l’e´laboration diagnostique des cancers de la teˆte et du cou, la TEP/TDM se re´ve`le un examen plus couˆteux que l’e´laboration courante mais, dans l’ensemble, elle permet de reáliser des ećonomies de couˆts en diminuant le nombre de traitements radicaux futiles. Aussi y a-t-il des couˆts et des avantages lie´s a` l’utilisation de la TEP/TDM dans le diagnostic et la stadification des cancers de la teˆte et du cou. Key words: cost-effectiveness, diagnosis, head and neck cancer, positron emission tomography/computed tomography

he past decade has seen significant advances in the treatment of head and neck cancer that have been facilitated by advances in research and technology. Despite these advances, detection of head and neck cancer is often late; consequently, up to two-thirds of patients present with advanced-stage disease (American Joint Committee on Cancer [AJCC] III–IVB). Initial staging and workup prior to consideration of therapeutic options conventionally consist of a history and head and neck examination, endoscopy, diagnostic imaging, and a general medical assessment. Accurate initial staging is essential as it determines the therapeutic options available for the patient, which could include a combination of surgery, radiotherapy, and/or chemotherapy. Traditionally, the diagnostic tests employed included computed tomography (CT) of the neck for characterization of the primary lesion and chest radiography for the detection of distant metastases. Depending on clinical suspicion for metastases, additional tests would have included CT of the chest, ultrasonography of the abdomen, magnetic resonance imaging (MRI), or wholebody positron emission tomography (PET). The presence of distant metastases at the initial staging changes treatment options from curative intent to a palliative one that may not include surgery. Positron emission tomography/computed tomography (PET/CT) is a newer imaging modality that combines whole-body PET using [18F]fluorodeoxyglucose (FDG), whole-body CT, and contrast high-definition CT of the head and neck. This has the advantage of combining the ability of FDG-PET to assess functional activity with the fine anatomic detailed afforded by CT. In the oncologic literature, PET/CT has been shown to improve diagnostic accuracy over anatomic and functional imaging independently.1–4 This diagnostic technology, however, has not gained wide acceptance owing to the increased test costs and the lack of widespread availability. We hypothesize that cost savings with PET/CT lie in detecting an increased number of distant metastases and in avoiding potentially futile surgeries in those patients. The objective of our study was to compare the cost-effectiveness

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of the traditional diagnostic workup to whole-body PET/CT (when used as a sole diagnostic tool) in the initial staging of advanced-stage head and neck cancer.

Methods The approval of the internal ethics review board of the University of Alberta was obtained. The study employed a population-based study design and consisted of four separate components: 1. A retrospective chart review was performed of all cases of advanced-stage (AJCC III–IVB) head and neck squamous cell carcinoma presenting to the practices of two head and neck surgeons (H.S., J.H.) at a tertiary care centre in one calendar year (2003). Patients without a tissue diagnosis were excluded. To ensure complete capture of patients, the comprehensive list of all patients with diagnostic codes corresponding to advanced-stage head and neck squamous cell carcinoma in 2003 was obtained from the Alberta Cancer Registry. Using this list, the surgeons’ charts were reviewed for pathology, imaging tests used in diagnostic workup, and treatment administered. Patients were followed until the last available visit, and data including the appearance of distant metastases and second primary tumours were tracked. 2. The cost of different diagnostic imaging tests was determined using estimates available from the Alberta Health Services (AHS) Diagnostic Imaging Department. An internal departmental cost per examination was calculated using data from the 2008/2009 fiscal year.5 This accounted for costs such as the radiologist’s interpretation fee, technologist’s cost, and supplies, as well as indirect expenses such as support staff. It did not include capital expenditures. 3. The cost of treatment was determined using the Alberta Case Cost Report for Hospital Activity (2005/ 2006) published by the Alberta Costing Partnership of AHS.6 This partnership between the constituent health regions and the Health Authority Funding and Financial Accountability Branch of AHS has developed

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patient-specific case costs for both inpatient and ambulatory care. Cases are grouped by linking activity data to cost data to provide appropriate summary information. Inpatient costs such as surgery and postoperative care are grouped into case mix groups (CMGs), and ambulatory care costs such as radiotherapy and chemotherapy are grouped by the Ambulatory Care Classification System (ACCS). Costing data accounted for patient-specific drug and supply costs; nonspecific drug allocation; functional centre direct costs such as cost of ward supplies, salaries of nurses, and ward administrators; and functional centre indirect costs such as facilities management, food services, and health records. Data did not account for expenditures not related to patient care, such as building improvements. To account for surgeon and anesthesiologist fees, an average fee for a prototypical head and neck squamous cell carcinoma resection and reconstruction was determined based on the AHS Schedule of Medical Benefits.7 4. A cost-benefit analysis was performed. Using the data available for the number of diagnostic tests performed using the traditional workup, an average cost of the diagnostic workup was determined. Next, the treatments instituted as a result of this workup and their corresponding costs were determined. This was then compared to a hypothetical cohort of the same characteristics using whole-body PET/CT as the sole diagnostic imaging tool. Using the sensitivity data available on PET/CT for the detection of distant metastases in head and neck squamous cell carcinoma,8 the additional number of metastases that could be detected was calculated. By switching these patients with distant metastatic disease to nonsurgical treatment, the change in the overall cost of treatment for the cohort could be calculated.

Results The retrospective chart review identified 87 patients presenting with advanced-stage head and neck squamous cell carcinoma in 2003 to the offices of both surgeons. Complete follow-up was available for 76 of these patients (87%), and complete data on the diagnostic workup was available for 49 patients. The cohort had an average age of 60 years, and 78% were male. At presentation, 31% had stage III disease and 69% had stage IV disease, with one distant metastasis detected at presentation. Surgical treatment was employed in 50 patients, with 1 patient

receiving chemoradiotherapy and surgery, 3 patients receiving surgery alone, and 46 patients receiving surgery and radiotherapy. Four patients did not receive any of the above treatments. The average follow-up was 2.93 years, with the detection of six additional metastases within 12 months. There were 14 local recurrences and 3 second primary tumours. This information is summarized in Table 1. Review of the diagnostic tests ordered showed that all 49 patients received CT of the neck, whereas chest radiography was performed in 45 patients. Non-neck CT scans ordered totalled 25, with 15 of these examining the chest. Seven MRIs, six sonograms, and three whole-body PET scans were obtained. Costs ranged from $61 for a chest radiograph to $344 for a whole-body PET scan. The cost of a whole-body PET/CT scan was $722. The number of tests, cost per examination, and total costs for the cohort are summarized in Table 2. Treatment costs were determined by identifying the CMGs most representative of the surgical procedures involved and averaging their total costs. The three CMGs identified were major head and neck procedures ($78,612), radical laryngectomy and glossectomy ($62,718), and reconstructive otolaryngologic procedures ($57,541). Average fees for two surgeons and the anesthesiologist were estimated to be $15,000. Adding this to the average hospital costs of the three CMGs, the cost per surgery was Table 1. Patient Characteristics Characteristic Total number of patients Complete follow-up Male Average age (yr) AJCC stage III AJCC stage IV Distant metastases at presentation Treatment (n 5 76) Surgery Surgery + radiotherapy Surgery + chemoradiotherapy Radiotherapy Radiotherapy + chemotherapy None Follow-up Average years Distant metastases in 12 mo Local recurrence Second primaries AJCC 5 American Joint Committee on Cancer.

n 87 76 68 60.1 23 53 1 3 46 1 8 (5 palliative) 14

2.93 6 14 3

Kurien et al, Cost-Effectiveness of PET/CT in Head and Neck Cancer

Table 2. Diagnostic Imaging Costs Diagnostic Test

n

Chest radiograph CT neck CT chest Other CT PET Ultrasonography MRI Total cost ($) Average cost for traditional workup ($) Cost for PET/CT workup ($)

45 49 15 10 3 6 7

Cost per Test ($) Total Cost ($) 61 200 200 200 344 179 342

2,745 9,800 3,000 2,000 1,032 1,074 2,394 22,045

450 722

CT 5 computed tomography; MRI 5 magnetic resonance imaging; PET 5 positron emission tomography.

determined to be $81,290. The cost of radiotherapy was $257 per visit, with an average of 32 visits, totalling $8,224. The cost of chemotherapy was $386, with an average of three cycles, giving a total of $1,158. Treatment costs are summarized in Table 3. For cost-benefit analysis from a health care insurer point of view, the average cost of the traditional workup per patient was $450. A whole-body PET/CT workup would cost an additional $272 per patient, resulting in an additional cost of $20,672 for the cohort. At 1 year, seven distant metastases, all in the lung, were identified, giving an incidence of 9.2%. This would place the sensitivity of detection of distant metastases at the initial presentation at 14.3%. Comparing this to the sensitivity of PET/CT in the detection of lung metastases in head and neck squamous cell carcinoma of 63%,8 an additional 3.4 metastases (conservatively rounded down to 3) could be detected. Table 3. Treatment Costs Treatment Type Surgical procedures (CMG) Major head and neck procedures Radical laryngectomy and glossectomy Reconstructive otolaryngologic procedures Average surgeon/anesthesia fees Average Nonsurgical procedures (ACCS) Radiotherapy Chemotherapy

Cost ($) 78,612 62,718 57,541 15,000 81,290 257 3 32 cycles 5 8,224 386 3 3 cycles 5 1,158

ACCS 5 Ambulatory Care Classification System; CMG 5 case mix group.

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Moving three additional patients from surgical treatment to nonsurgical treatment, assuming that they would receive radiotherapy—the more expensive of the two nonsurgical treatments—$219,198 could be saved. Accounting for the additional costs of the workup itself, an average of $2,612 could be saved per patient in this cohort.

Discussion The advent of FDG-PET functional imaging in the 1980s brought with it a significant change in the diagnosis and management of cancer patients. PET alone has been diagnostically effective in multiple types of malignancies9–11 but has been limited in assessment of primary lesions in head and neck cancer owing to the intricate regional anatomy and baseline physiologic uptake of FDG in the brain and various tissues of the head and neck.12 Combined PET/CT scanners have the benefit of providing anatomic and functional data simultaneously,13,14 thereby improving diagnostic accuracy. This has been demonstrated in several regions of the body,10,11,15,16 including the head and neck, where studies have shown altered clinical decision making as a result.17–19 Reluctance to more broadly adopt this technology has centred around concerns over increased capital and operating costs and a lack of widespread availability. Cost-effectiveness studies have been performed in lung, breast, colon, and pancreatic cancers, with positive results suggesting cost savings. The literature on cost-effectiveness in head and neck cancers has been limited. Senft and colleagues demonstrated that whole-body PET and chest CT had higher sensitivity, 63%, for distant metastases than either modality alone.8 This increased sensitivity of PET/ CT in detecting distant metastasis has been demonstrated to be cost-effective in pancreatic cancer patients.20 The incidence of distant metastases detection through conventional means at presentation in our study was 14%; this is in agreement with the incidence reported in the literature, which ranges from 2 to 18%.8 These low detection rates for distant metastases suggest that there is significant room for improvement for tests with superior sensitivity that can spare patients the morbidity of aggressive and futile treatment protocols. Our results demonstrate that the use of PET/CT for head and neck cancers would indeed be cost-effective. The cost of using PET/CT, although higher than conventional modalities, ultimately leads to savings because the cost of a futile surgical intervention is orders of magnitude more expensive than the testing itself. Further prospective

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studies are needed to demonstrate the cost-effectiveness of PET/CT as this can positively impact its availability as well. Some of the acknowledged weaknesses of this study include the fact that it is partially retrospective in nature and that the cost estimates are based on global figures published by government agencies. These cost figures may not be reflective of our specific patient cohort but would be representative of our patient population.

Conclusions PET/CT is a more expensive test when used as the sole entity for diagnostic workup of head and neck cancer but results in an overall cost savings by reducing the number of futile radical treatments. There is a cost benefit to the use of PET/CT as the diagnostic and staging test for head and neck cancer patients.

Acknowledgement Financial disclosure of authors and reviewers: None reported.

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