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To CT or not to CT: Questioning the Cost-Effectiveness of CT Thorax in Head and Neck Cancers

To CT or not to CT: Questioning the Cost-Effectiveness of CT Thorax in Head and Neck Cancers Computed tomography (CT) scan has been an integral part of the diagnostic workup for patients with head and neck squamous cell carcinoma. Our study was designed to find out the incidence of distant metastasis and second primary tumor and to cor - relate the cost-effectiveness of CT thorax in detecting the same. This study was conducted among 326 cancer patients who visited our center with curative intent in the year 2021, with lesions in various head and neck subsites. Data were collected based on their pathological TNM staging and the presence of distant metastasis as evident on their CT thorax imaging with various variables related to the disease. Incremental cost-effectiveness ratio (ICER) was calculated for detecting a single metastatic deposit and second primary tumor in terms of Indian currency and was correlated to each subsite and stage of disease at presentation. Out of these 326 patients, 281 patients were included in our study after considering the inclusion criteria, and among these 281 patients, 235 of them underwent CT thorax for metastatic workup. No patient was found to have a second primary. Metastases were found in 12 patients. The site of primary lesion and clinical tumor (cT) staging were found to be significantly influencing the incidence of metastasis on CT thorax. ICER was least for larynx, pharynx, and paranasal sinuses and was highest for oral cavity primaries and early-stage disease. As per our observations and results of ICER, CT thorax is indeed a valuable modality but should be used judiciously when it comes to initial diagnostic workup. Keywords CT thorax · Distant metastatic workup · CT scan · Computed tomography · Second primary tumor · Cost effectiveness * Preethi S. Shetty Priya P. Sankaran preethi.sshetty@manipal.edu priya.psankaran@gmail.com Nawaz Usman G. Somu nawaz.usman@manipal.edu somu.g@manipal.edu Punit Singh Dikhit Department of Surgical Oncology, Manipal Academy dikhit.punit@gmail.com of Higher Education (MAHE), Manipal Comprehensive Diksha Dinker Cancer Care Centre, Kasturba Medical College, Manipal, dr.dikshadinker@gmail.com Karnataka 576401, India Naveena A. N. Kumar Department of Radiodiagnosis and Imaging, Manipal naveenkumar.an@manipal.edu Academy of Higher Education (MAHE), Kasturba Medical College Manipal, Manipal, Karnataka 576104, India Akhil Palod drakhilpalod@gmail.com Department of Hospital Administration, Kasturba Medical College Manipal, Manipal, Karnataka 576104, India Koteshwara Prakashini prakashini.k@manipal.edu Vol.:(0123456789) 1 3 Indian Journal of Surgical Oncology potentially deleterious effects of added radiation exposure. Introduction Henceforth, this study was conducted in order to evaluate the cost-effectiveness of CT thorax as a metastatic workup. Squamous cell carcinoma of the head and neck still remains a major health-related problem, particularly so in South Asian countries, including India. Overall disease prognosis has not improved much over the years despite the introduc- Materials and Methods tion of new diagnostic modalities and new treatment strate- gies. Around 25% of deaths in HNSCC can be attributed to The electronic medical records of patients were accessed the second primary tumor (SPT) and distant lung metasta- for the demographic details, clinical staging, CT findings, sis (DM) [1]. The most common site for DM deposit from and final tumor board decision. All patients above 18 years HNSCC is the lungs, with an incidence of around 8 to 15% of age with biopsy-proven squamous cell carcinoma (SCC) as described in multiple clinical studies [2]. Primary lung of HNC attending the Oncology out-patient department cancers, which can be included under SPT, account for about (OPD) (i.e., Surgical Oncology, Radiation Oncology, and 23% of patients with HNSCC [2]. Often, the treating surgeon Medical Oncology) between the period January 2021 and comes across situations where radical curative intent surgery December 2021 were screened for the inclusion and exclu- for locoregionally advanced cancer is ultimately a failure sion criteria (Table 1). because of an SPT or a DM focus. The CT thorax of the eligible patients was reviewed by CT scan has drastically changed the treatment strategies two radiologists (one is a tumor board member and another in the new era and is widely used in the field of oncology to independent senior radiologist) for the presence of pulmo- assess the primary site of head and neck cancer, nodal dis- nary metastases, second primary lung, mediastinal nodes, ease, and staging as a part of the established TNM staging and other site metastases. Pulmonary nodules more than 5 system. CT thorax as an imaging modality is an extremely mm, without spiculated margins, smooth located periph- useful tool for assessing primary tumor, nodal metastasis, erally, mediastinal lymph nodes >/= 10 mm, and solitary and distant metastasis. This widely available modality has spiculated lesion centrally located >/= 10 mm were noted given the surgeons the ability to prognosticate the patient as metastatic. Histologic confirmation of metastasis was during the initial screening itself. not mandatory. An important question remains as to how often one The details were then analyzed using the SPSS software needs to do pre- and postoperative screening for distant version 26. Factors influencing the incidence of metastasis metastases. Although the National Comprehensive Cancer were analyzed by logistic regression. For estimating the Network® (NCCN®) gives a picture regarding CT thorax cost-benefit analysis, the absolute cost of CECT thorax frequency and indications, these blanket guidelines can- and chest X-rays was obtained from the hospital billing not be applied to all patients, especially the patients in section. The yield of each diagnostic modality was defined the Indian subcontinent [3]. A preoperative chest X-ray is as the number of patients with metastasis divided by the warranted in all cases as a part of a presurgical workup. number of patients going through the diagnosis strategy. If the primary tumor and nodal status place the patient at Cost-effectiveness was measured using the incremental high risk for pulmonary metastasis, a preoperative com- cost-effectiveness ratio (ICER) and was calculated as puted tomography scan of the chest is indicated. As cru- shown in Fig.  1. This estimates the additional cost per cial as it may sound, in a developing country like India, it additional patient with metastasis detected by CECT tho- still contributes to burdening the vast majority of patients rax over chest X-ray. who belong to a poor socio-economic status along with the Table 1 Inclusion and exclusion Inclusion criteria Exclusion criteria criteria of the study Histopathology Squamous cell carcinoma (SCC) Other pathology, i.e., lymphoma, salivary gland tumor, and melanoma Site Oral cavity, lip, oropharynx, Nasopharyngeal, unknown primary neck, thyroid larynx, hypopharynx Primary/recurrent Primary Recurrent Mode of imaging CECT thorax PETCECT, if done as primary scan 1 3 Indian Journal of Surgical Oncology Fig. 1 Computation of cost effectiveness of CECT thorax over Chest Xray using incremental cost effectiveness ratio (ICER) The average age of the patient with or without metasta- Results sis on CT thorax was similar (59.2 +/− 11.3 years vs 56.7 +/− 11.7 years, respectively). The incidence of metastasis A total of 326 patients with biopsy-proven HNSCC on CT thorax was similar amongst the gender group too attended the Oncology OPD between January 2021 and (6% for males and 5.9% for females). The highest incidence December 2021 and were screened for eligibility for the of metastasis on CT thorax was noted amongst smokers study. Of these, 281 patients fit the aforementioned crite- (12.1%), followed by tobacco chewer (7.7%) and alcohol ria. Amongst them, 235 patients had undergone CT thorax intake (6.3%). There was no metastasis seen in patients who as a part of staging workup and, finally, 200 patients had were purely betel nut chewers. Patients with no tobacco/ locoregionally advanced clinical staging (AJCC 8th Edi- alcohol intake had an incidence of metastasis at 3.2%. tion Stage III & IV). The incidence of the metastases on CT thorax with A total of 12 patients of the 200 (6%) were found to respect to the site of primary, clinical T, and N staging has have unequivocal metastases on the CT thorax. Of these, been elaborated in Table 2. 7 (59%) had pulmonary metastasis alone, 2 (17%) had On univariate analysis, the site of the primary lesion and liver metastasis alone, and one (8%) had bony metastasis cT staging was found to be significantly influencing the inci- alone. Two patients had multiple organ metastases, i.e., dence of metastasis on CT thorax (p = 0.012 and p = 0.028, pulmonary + liver and liver + splenic metastases each. No respectively). Clinical N staging was not found to be signifi- patient was found to have a synchronous second primary. cantly affecting the development of metastasis. Furthermore, These 12 patients had a change in disease management on multivariate and logistic regression analysis, cT staging from curative to palliative intent. Table 2 Incidence of metastasis Metastasis on CECT thorax Total number on CECT thorax based on of patients (n = clinical staging and site of 200) primary Present (n = 12) Absent (n = 188) Age (in years) 59.2 +/− 11.3 56.7 +/− 11.7 P-value = 0.47 Gender P-value = 1.00   Male 10 (6%) 156 (94%) 166   Female 2 (5.9%) 10 (94.1%) 12 Habits P-value = 0.32   None 2 (3.2%) 60 (96.8%) 62   Betel nut chewing 0 21 (100%) 21   Alcohol 2 (6.3%) 30 (93.8%) 32   Tobacco chewing 4 (7.7%) 48 (92.3%) 52   Smoking 4 (12.1%) 29 (87.9%) 33 cTumor stage P-value = 0.028   Early (T1, T2) 1 (2.9%) 33 (97.1%) 34   Advanced (T3, T4) 11 (6.6%) 155 (93.4%) 166 cNodal stage P-value = 0.471   N0 1 (1.9%) 52 (98.1%) 53   N+ 11 (7.5%) 136 (92.5%) 147 Site of primary P-value = 0.012   Oral cavity and lip 4 (3.6%) 106 (96.4%) 110   Oropharynx 1 (14.3%) 6 (85.7%) 7   Larynx 4 (22.2%) 14 (77.8%) 18   Hypopharynx 2 (3.3%) 58 (96.7%) 60   Paranasal sinus 1 (20%) 4 (80%) 5 1 3 Indian Journal of Surgical Oncology alone was found to be significant (HR–4.22. CI: 1.07–16.54, Another study by Reiner et  al. to evaluate the role of p-value = 0.039). CT thorax in detecting DM foci and SPT in patients with The CECT thorax was evaluated against a chest X-ray for HNSCC involved 189 patients, of which 63 patients had cost-benefit analysis (Table  3). laryngeal primaries, 53 had pharyngeal primaries and 72 The average cost of a CECT thorax was Rs 7000 per had oral cavity primaries. Out of these patients, SPT was patient, and that of a chest X-ray was Rs 200 per patient. The detected on the CT chest in 4 patients with laryngeal malig- chest X-ray did not pick up any metastasis, while the yield of nancies and 6 patients with pharyngeal malignancies, with CECT thorax was 6%. Based on this, an ICER of Rs 113,333 no evidence of SPT in oral cavity subsets, while DM was was noted. This represents the additional cost of using CECT found in 6 patients with laryngeal malignancies, 4 patients thorax over chest X-rays to identify one additional patient of pharyngeal malignancies, and 11 patients of oral cavity with metastasis. On subgroup analysis, cT stage, location of subsets, all of which were stage IV disease. Although this the primary site was found to significantly affect the ICER. aforementioned study was designed to evaluate the efficiency The ICER was least for cT3/4 lesions (Rs 97,142 per patient) of chest X-ray in detecting lung abnormalities as compared and doubled for cT1/2 lesions. Similarly, their ICER was sig- to CT chest, and they showed that CT thorax was a superior nificantly lower for patients with oropharyngeal, laryngeal, modality, they did not evaluate the cost-effectiveness of CT and paranasal sinus primaries compared to the oral cavity scan for detecting single SPT or DM [1]. and hypo-pharyngeal primaries. Similar findings were suggested by Fukuhara et al. where the supremacy of CT chest as compared to chest X-ray was advocated but the primary subset of patients was again laryngeal malignancies, with oral cavity subsets being only Discussion about 16% of the total study group. They were able to detect 23% of lung nodules (SPT or DM), which changed the treat- The aim of our study was to evaluate the cost-effectiveness ment plan, thus advocating CT thorax during initial screen- of CT chest during initial screening to search for SPT and ing but missing on the part of cost-effectiveness based on DM foci, especially in financially constrained situations as head and neck subsites and staging [5]. seen in India. These guidelines, emphasizing the need for CT The rate of detection of distant metastasis at initial pres- chest in newly diagnosed HNSCC, have not been evaluated entation ranged between 1.5 to 20% [6, 7]. As compared to in terms of cost-effectiveness and subsite-based analysis. We these studies, in our study data the incidence of DM was came across multiple studies on detection rates of CT scans around 6% while there was no SPTs. A study by Nagarkar for SPT and DM. A study by Ong et al. where significant et al. reported findings similar to ours, with the incidence of emphasis to detect SPT and DM was given on the CT chest DM being 3.2% while not picking up SPTs [8]. Advanced T in initial screening involved around 47% of patients with and N stages were found to significantly correlate with the laryngeal malignancies while only 28% of patients belong rate of pickup of DMs. This is also echoed in the NCCN to the oral subset [4]. guidelines that mention CT thorax as a metastatic work-up in Table 3 Cost benefit analysis CECT thorax Chest X-ray ICER of CECT thorax vs chest X-ray Cost per Yield (Y ) Cost per Yield (Y ) (C – C )/(Y – Y ) T X T x T X patient (C ) patient (C ) T x All patients Rs 7000 0.06 Rs 200 0 Rs 113,333 cTumor stage   T1/2 Rs 7000 0.03 Rs 200 0 Rs 226,666   T3/4 Rs 7000 0.07 Rs 200 0 Rs 97,142 cNodal stage   N0/1 Rs 7000 0.04 Rs 200 0 Rs 170,000   N2/3 Rs 7000 0.07 Rs 200 0 Rs 97,142 Site of primary   Oral cavity and lip Rs 7000 0.04 Rs 200 0 Rs 170,000   Oropharynx Rs 7000 0.14 Rs 200 0 Rs 48,571   Larynx Rs 7000 0.22 Rs 200 0 Rs 30,909   Hypopharynx Rs 7000 0.03 Rs 200 0 Rs 226,666   Paranasal sinus Rs 7000 0.20 Rs 200 0 Rs 34,000 1 3 Indian Journal of Surgical Oncology higher T and N stages [3]. We noted a significant association patients. And only 2 of them smoked 30 pack years. This between cT stages and subsite of the primary tumor, while could explain why we did not find any second primaries N status failed to correlate significantly. These discrepancies in our study. warrant the need for reassessing the need for CT thorax as On cost effectiveness analysis, the ICER was most a routine distant metastatic workup for all HNSCC patients. efficient for subsites like larynx, oropharynx, and parana- The incidence of DM in head and neck cancers is rela- sal sinuses and for locoregionally advanced disease. Our tively small compared with other malignancies like stomach, analysis showed that the ICER of performing CT scan pancreas, lung, or breast [7]. This range of variation in the across all comers was a hefty 133,000 Indian rupees. With incidence of DM can possibly be explained by the fact that increasing cost of health care services, every screening all these studies have different numbers of populations of procedure must be justified not only based on sensitivity primary index tumors. but cost efficiency as well. Interestingly, in our study as well as in the aforemen- Luke Tan et al. published a study to evaluate the benefit tioned studies, the larynx was a common site associated with of CT chest as a screening tool in patients with HNSCC. increased risk of DM and SPT as compared to oral cavity A total of 20 patients were included in the study, and they subsites. If this associated difference was because of any concluded that even after adding an additional cost of particular habit history or any other risk factor was beyond $13,314, CT chest did not add to the extra sensitivity for the scope of our study. detecting DM and SPT [13]. NCCN guidelines recommend CT scan in locoregionally Although the efficiency and sensitivity of CT chest for advanced HNSCC . However, part of the justification for detecting DM and SPT are proven and have been included this recommendation has been the claim that CT also has in internationally accepted guidelines, the blanket use the additional advantage of picking SPTs, but on careful of CT chest for all HNSCC patients is not cost-effective evaluation of the literature, we found that the incidence of as per our experience. We found a statistically signifi- SPT was low at 1.5% in the study by Fukuhara et al. [5] and cant correlation in terms of ICER between DM and cT4 5.7% among 1086 patients in a study by Shah et al. [9]. Even oral disease with a value of 170,000/−, for oropharynx in an extensive literature review by Warren and Gates, where and hypopharynx 48,571/− and 226,666/− respectively, a total of 1259 cases were studied in detail, a total incidence for larynx 30,909/− and for paranasal sinuses 34,000/−. of 3.5% of SPT was noted. In our data of 281 patients, we Another factor that had a favorable ICER in our study was did not find even a single case of SPT, thereby questioning a nodal disease, i.e., N0/N1 disease vs N2/N3 disease, but the claim that CT thorax has the added advantage of picking this difference was statistically insignificant. up SPTs [10]. We did a cost analysis based on our findings and calcu- lated the ICER, which showed differences in cost-effective - ness based on subsites. This difference was most pronounced Conclusion in the oral cavity subsite and early-stage tumor and for N0/ N1 stage disease. The superiority of a CT chest over a con- In developing countries with limited resources and a high ventional X-ray has been established beyond doubt and this burden of disease, it is the need of the hour to cut down is reflected in the NCCN guidelines where preoperative CT on non-cost-effective diagnostic modalities. Although our chest has been advised during initial workup to look for DM, study design and findings are not robust enough to make SPT, and mediastinal lymphadenopathy [3]. However, in a rigid recommendations, they do suggest that there is a country like ours, there is a need to justify the additional scope to make CT thorax as a diagnostic modality more financial burden this approach entails. Our study data and cost-effective. CT thorax can be used in locally advanced results reflect a way that can be used for modifying existing HNSCC as a part of staging workup; however, our cost guidelines. The majority of the patient population in our analysis has not supported use in all the stages and all study comprised of the oral cavity subsite, which contrib- subsites. The need of the hour is to design larger, prefer- uted to only around 3.6% of the total detected DMs, while ably prospective studies so that we can identify the subsets laryngeal cancers contributed to 22% of the total detected that benefit most from CT scan as a screening modality for DMs. Interestingly, all the patients in oral cavity subsites metastases and avoid them in the rest, thereby decreasing who had metastatic deposits (4 patients) belong to locore- the financial burden on the healthcare and also decreasing gionally advanced stages. the deleterious effects of radiation exposure. The NLST trial showed the benefit of CT scan screen- ing in people with a high risk of lung cancer (one of their Author Contribution Conceptualization: Dr Nawaz Usman and Dr inclusion criteria was cigarette smoking for 30 pack years) Preethi S Shetty; methodology: Dr Punit S Dikhit and Dr Diksha [11, 12]. We only had smoking as a habit in 16.5% of our 1 3 Indian Journal of Surgical Oncology Dinker; formal analysis and investigation: Dr Punit S Dikhit and Dr 2. Hsu Y, Chu P, Liu J, Lan M, Chang S, Tsai T et al (2008) Role Naveena AN Kumar; writing—original draft preparation: Dr Naveena of chest computed tomography in head and neck cancer. Arch AN Kumar, Dr Punit S Dikhit, and Dr Akhil Palod; writing—review Otolaryngol-Head Neck Surg 134(10):1050 and editing: Dr Prakashini K and Dr Priya P Sankaran; Resources: Dr 3. National Comprehensive Cancer Network. Head and Neck Can- Somu G; Supervision: Dr Nawaz Usman and Dr Naveena Kumar AN. cers (Version 2.2022 — April 26, 2022). https:// www. nccn. org/ profe ssion als/ physi cian_ gls/ pdf/ head- and- neck. pdf. Accessed 1 June 2022 Funding Open access funding provided by Manipal Academy of 4. Ong T, Kerawala C, Martin I, Stafford F (1999) The role of thorax Higher Education, Manipal imaging in staging head and neck squamous cell carcinoma. J Cranio-Maxillofac Surg 27(6):339–344 Declarations 5. Fukuhara T, Fujiwara K, Fujii T, Takeda K, Matsuda E, Hasegawa K et al (2015) Usefulness of chest CT scan for head and neck Ethics Approval All human and animal studies have been approved by cancer. Auris Nasus Larynx 42(1):49–52 the appropriate ethics committee/institutional review board (IRB) of 6. Ferlito A, Shaha A, Silver C, Rinaldo A, Mondin V (2001) Inci- the KMC ethical committee board and have therefore been performed dence and sites of distant metastases from head and neck cancer. in accordance with the ethical standards laid down in the 1964 Dec- ORL. 63(4):202–207 laration of Helsinki and its later amendments, along with the ethics 7. Garavello W, Ciardo A, Spreafico R, Gaini R (2006) Risk factors committee. for distant metastases in head and neck squamous cell carcinoma. Arch Otolaryngol-Head Neck Surg 132(7):762 Consent for Publication Written informed consent for publication of 8. Raj VN, Ashvin PW, Gauri SK, Mayank P, Aditya MM (2017) their clinical details was obtained from the patient. Incidence and Prognostic Factors in Distant Metastasis from Pri- mary Head and Neck Cancer-An Institutional Experience. J Head Neck Spine Surg 1(5):555571 Conflict of Interest The authors declare no competing interests. 9. Shah S, Applebaum E (2000) Lung cancer after head and neck can- cer: role of chest radiography. Laryngoscope 110(12):2033–2036 Open Access This article is licensed under a Creative Commons Attri- 10. Warren S, Gates O (1932) Multiple primary malignant tumors: bution 4.0 International License, which permits use, sharing, adapta- a survey of the literature and a statistical study. Am J Cancer tion, distribution and reproduction in any medium or format, as long 16:1358–414 as you give appropriate credit to the original author(s) and the source, 11. The National Lung Screening Trial (2011) overview and study provide a link to the Creative Commons licence, and indicate if changes design. Radiology 258(1):243–253 were made. The images or other third party material in this article are 12. National Lung Screening Trial Research Team, Church TR, included in the article's Creative Commons licence, unless indicated Black WC, Aberle DR, Berg CD, Clingan KL, Duan F, Fager- otherwise in a credit line to the material. If material is not included in strom RM, Gareen IF, Gierada DS, Jones GC, Mahon I, Marcus the article's Creative Commons licence and your intended use is not PM, Sicks JD, Jain A, Baum S (2013) Results of initial low-dose permitted by statutory regulation or exceeds the permitted use, you will computed tomographic screening for lung cancer. N Engl J Med need to obtain permission directly from the copyright holder. To view a 368(21):1980–1991 copy of this licence, visit http://cr eativ ecommons. or g/licen ses/ b y/4.0/ . 13. Tan L, Greener C, Seikaly H, Rassekh C, Calhoun K (1999) Role of screening chest computed tomography in patients with advanced head and neck cancer. Otolaryngol-Head Neck Surg 120(5):689–692 References Publisher's Note Springer Nature remains neutral with regard to 1. Reiner B, Siegel E, Sawyer R, Brocato R, Maroney M, Hooper F jurisdictional claims in published maps and institutional affiliations. (1997) The impact of routine CT of the chest on the diagnosis and management of newly diagnosed squamous cell carcinoma of the head and neck. Am J Roentgenol 169(3):667–671 1 3 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Indian Journal of Surgical Oncology Springer Journals

To CT or not to CT: Questioning the Cost-Effectiveness of CT Thorax in Head and Neck Cancers

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Abstract

Computed tomography (CT) scan has been an integral part of the diagnostic workup for patients with head and neck squamous cell carcinoma. Our study was designed to find out the incidence of distant metastasis and second primary tumor and to cor - relate the cost-effectiveness of CT thorax in detecting the same. This study was conducted among 326 cancer patients who visited our center with curative intent in the year 2021, with lesions in various head and neck subsites. Data were collected based on their pathological TNM staging and the presence of distant metastasis as evident on their CT thorax imaging with various variables related to the disease. Incremental cost-effectiveness ratio (ICER) was calculated for detecting a single metastatic deposit and second primary tumor in terms of Indian currency and was correlated to each subsite and stage of disease at presentation. Out of these 326 patients, 281 patients were included in our study after considering the inclusion criteria, and among these 281 patients, 235 of them underwent CT thorax for metastatic workup. No patient was found to have a second primary. Metastases were found in 12 patients. The site of primary lesion and clinical tumor (cT) staging were found to be significantly influencing the incidence of metastasis on CT thorax. ICER was least for larynx, pharynx, and paranasal sinuses and was highest for oral cavity primaries and early-stage disease. As per our observations and results of ICER, CT thorax is indeed a valuable modality but should be used judiciously when it comes to initial diagnostic workup. Keywords CT thorax · Distant metastatic workup · CT scan · Computed tomography · Second primary tumor · Cost effectiveness * Preethi S. Shetty Priya P. Sankaran preethi.sshetty@manipal.edu priya.psankaran@gmail.com Nawaz Usman G. Somu nawaz.usman@manipal.edu somu.g@manipal.edu Punit Singh Dikhit Department of Surgical Oncology, Manipal Academy dikhit.punit@gmail.com of Higher Education (MAHE), Manipal Comprehensive Diksha Dinker Cancer Care Centre, Kasturba Medical College, Manipal, dr.dikshadinker@gmail.com Karnataka 576401, India Naveena A. N. Kumar Department of Radiodiagnosis and Imaging, Manipal naveenkumar.an@manipal.edu Academy of Higher Education (MAHE), Kasturba Medical College Manipal, Manipal, Karnataka 576104, India Akhil Palod drakhilpalod@gmail.com Department of Hospital Administration, Kasturba Medical College Manipal, Manipal, Karnataka 576104, India Koteshwara Prakashini prakashini.k@manipal.edu Vol.:(0123456789) 1 3 Indian Journal of Surgical Oncology potentially deleterious effects of added radiation exposure. Introduction Henceforth, this study was conducted in order to evaluate the cost-effectiveness of CT thorax as a metastatic workup. Squamous cell carcinoma of the head and neck still remains a major health-related problem, particularly so in South Asian countries, including India. Overall disease prognosis has not improved much over the years despite the introduc- Materials and Methods tion of new diagnostic modalities and new treatment strate- gies. Around 25% of deaths in HNSCC can be attributed to The electronic medical records of patients were accessed the second primary tumor (SPT) and distant lung metasta- for the demographic details, clinical staging, CT findings, sis (DM) [1]. The most common site for DM deposit from and final tumor board decision. All patients above 18 years HNSCC is the lungs, with an incidence of around 8 to 15% of age with biopsy-proven squamous cell carcinoma (SCC) as described in multiple clinical studies [2]. Primary lung of HNC attending the Oncology out-patient department cancers, which can be included under SPT, account for about (OPD) (i.e., Surgical Oncology, Radiation Oncology, and 23% of patients with HNSCC [2]. Often, the treating surgeon Medical Oncology) between the period January 2021 and comes across situations where radical curative intent surgery December 2021 were screened for the inclusion and exclu- for locoregionally advanced cancer is ultimately a failure sion criteria (Table 1). because of an SPT or a DM focus. The CT thorax of the eligible patients was reviewed by CT scan has drastically changed the treatment strategies two radiologists (one is a tumor board member and another in the new era and is widely used in the field of oncology to independent senior radiologist) for the presence of pulmo- assess the primary site of head and neck cancer, nodal dis- nary metastases, second primary lung, mediastinal nodes, ease, and staging as a part of the established TNM staging and other site metastases. Pulmonary nodules more than 5 system. CT thorax as an imaging modality is an extremely mm, without spiculated margins, smooth located periph- useful tool for assessing primary tumor, nodal metastasis, erally, mediastinal lymph nodes >/= 10 mm, and solitary and distant metastasis. This widely available modality has spiculated lesion centrally located >/= 10 mm were noted given the surgeons the ability to prognosticate the patient as metastatic. Histologic confirmation of metastasis was during the initial screening itself. not mandatory. An important question remains as to how often one The details were then analyzed using the SPSS software needs to do pre- and postoperative screening for distant version 26. Factors influencing the incidence of metastasis metastases. Although the National Comprehensive Cancer were analyzed by logistic regression. For estimating the Network® (NCCN®) gives a picture regarding CT thorax cost-benefit analysis, the absolute cost of CECT thorax frequency and indications, these blanket guidelines can- and chest X-rays was obtained from the hospital billing not be applied to all patients, especially the patients in section. The yield of each diagnostic modality was defined the Indian subcontinent [3]. A preoperative chest X-ray is as the number of patients with metastasis divided by the warranted in all cases as a part of a presurgical workup. number of patients going through the diagnosis strategy. If the primary tumor and nodal status place the patient at Cost-effectiveness was measured using the incremental high risk for pulmonary metastasis, a preoperative com- cost-effectiveness ratio (ICER) and was calculated as puted tomography scan of the chest is indicated. As cru- shown in Fig.  1. This estimates the additional cost per cial as it may sound, in a developing country like India, it additional patient with metastasis detected by CECT tho- still contributes to burdening the vast majority of patients rax over chest X-ray. who belong to a poor socio-economic status along with the Table 1 Inclusion and exclusion Inclusion criteria Exclusion criteria criteria of the study Histopathology Squamous cell carcinoma (SCC) Other pathology, i.e., lymphoma, salivary gland tumor, and melanoma Site Oral cavity, lip, oropharynx, Nasopharyngeal, unknown primary neck, thyroid larynx, hypopharynx Primary/recurrent Primary Recurrent Mode of imaging CECT thorax PETCECT, if done as primary scan 1 3 Indian Journal of Surgical Oncology Fig. 1 Computation of cost effectiveness of CECT thorax over Chest Xray using incremental cost effectiveness ratio (ICER) The average age of the patient with or without metasta- Results sis on CT thorax was similar (59.2 +/− 11.3 years vs 56.7 +/− 11.7 years, respectively). The incidence of metastasis A total of 326 patients with biopsy-proven HNSCC on CT thorax was similar amongst the gender group too attended the Oncology OPD between January 2021 and (6% for males and 5.9% for females). The highest incidence December 2021 and were screened for eligibility for the of metastasis on CT thorax was noted amongst smokers study. Of these, 281 patients fit the aforementioned crite- (12.1%), followed by tobacco chewer (7.7%) and alcohol ria. Amongst them, 235 patients had undergone CT thorax intake (6.3%). There was no metastasis seen in patients who as a part of staging workup and, finally, 200 patients had were purely betel nut chewers. Patients with no tobacco/ locoregionally advanced clinical staging (AJCC 8th Edi- alcohol intake had an incidence of metastasis at 3.2%. tion Stage III & IV). The incidence of the metastases on CT thorax with A total of 12 patients of the 200 (6%) were found to respect to the site of primary, clinical T, and N staging has have unequivocal metastases on the CT thorax. Of these, been elaborated in Table 2. 7 (59%) had pulmonary metastasis alone, 2 (17%) had On univariate analysis, the site of the primary lesion and liver metastasis alone, and one (8%) had bony metastasis cT staging was found to be significantly influencing the inci- alone. Two patients had multiple organ metastases, i.e., dence of metastasis on CT thorax (p = 0.012 and p = 0.028, pulmonary + liver and liver + splenic metastases each. No respectively). Clinical N staging was not found to be signifi- patient was found to have a synchronous second primary. cantly affecting the development of metastasis. Furthermore, These 12 patients had a change in disease management on multivariate and logistic regression analysis, cT staging from curative to palliative intent. Table 2 Incidence of metastasis Metastasis on CECT thorax Total number on CECT thorax based on of patients (n = clinical staging and site of 200) primary Present (n = 12) Absent (n = 188) Age (in years) 59.2 +/− 11.3 56.7 +/− 11.7 P-value = 0.47 Gender P-value = 1.00   Male 10 (6%) 156 (94%) 166   Female 2 (5.9%) 10 (94.1%) 12 Habits P-value = 0.32   None 2 (3.2%) 60 (96.8%) 62   Betel nut chewing 0 21 (100%) 21   Alcohol 2 (6.3%) 30 (93.8%) 32   Tobacco chewing 4 (7.7%) 48 (92.3%) 52   Smoking 4 (12.1%) 29 (87.9%) 33 cTumor stage P-value = 0.028   Early (T1, T2) 1 (2.9%) 33 (97.1%) 34   Advanced (T3, T4) 11 (6.6%) 155 (93.4%) 166 cNodal stage P-value = 0.471   N0 1 (1.9%) 52 (98.1%) 53   N+ 11 (7.5%) 136 (92.5%) 147 Site of primary P-value = 0.012   Oral cavity and lip 4 (3.6%) 106 (96.4%) 110   Oropharynx 1 (14.3%) 6 (85.7%) 7   Larynx 4 (22.2%) 14 (77.8%) 18   Hypopharynx 2 (3.3%) 58 (96.7%) 60   Paranasal sinus 1 (20%) 4 (80%) 5 1 3 Indian Journal of Surgical Oncology alone was found to be significant (HR–4.22. CI: 1.07–16.54, Another study by Reiner et  al. to evaluate the role of p-value = 0.039). CT thorax in detecting DM foci and SPT in patients with The CECT thorax was evaluated against a chest X-ray for HNSCC involved 189 patients, of which 63 patients had cost-benefit analysis (Table  3). laryngeal primaries, 53 had pharyngeal primaries and 72 The average cost of a CECT thorax was Rs 7000 per had oral cavity primaries. Out of these patients, SPT was patient, and that of a chest X-ray was Rs 200 per patient. The detected on the CT chest in 4 patients with laryngeal malig- chest X-ray did not pick up any metastasis, while the yield of nancies and 6 patients with pharyngeal malignancies, with CECT thorax was 6%. Based on this, an ICER of Rs 113,333 no evidence of SPT in oral cavity subsets, while DM was was noted. This represents the additional cost of using CECT found in 6 patients with laryngeal malignancies, 4 patients thorax over chest X-rays to identify one additional patient of pharyngeal malignancies, and 11 patients of oral cavity with metastasis. On subgroup analysis, cT stage, location of subsets, all of which were stage IV disease. Although this the primary site was found to significantly affect the ICER. aforementioned study was designed to evaluate the efficiency The ICER was least for cT3/4 lesions (Rs 97,142 per patient) of chest X-ray in detecting lung abnormalities as compared and doubled for cT1/2 lesions. Similarly, their ICER was sig- to CT chest, and they showed that CT thorax was a superior nificantly lower for patients with oropharyngeal, laryngeal, modality, they did not evaluate the cost-effectiveness of CT and paranasal sinus primaries compared to the oral cavity scan for detecting single SPT or DM [1]. and hypo-pharyngeal primaries. Similar findings were suggested by Fukuhara et al. where the supremacy of CT chest as compared to chest X-ray was advocated but the primary subset of patients was again laryngeal malignancies, with oral cavity subsets being only Discussion about 16% of the total study group. They were able to detect 23% of lung nodules (SPT or DM), which changed the treat- The aim of our study was to evaluate the cost-effectiveness ment plan, thus advocating CT thorax during initial screen- of CT chest during initial screening to search for SPT and ing but missing on the part of cost-effectiveness based on DM foci, especially in financially constrained situations as head and neck subsites and staging [5]. seen in India. These guidelines, emphasizing the need for CT The rate of detection of distant metastasis at initial pres- chest in newly diagnosed HNSCC, have not been evaluated entation ranged between 1.5 to 20% [6, 7]. As compared to in terms of cost-effectiveness and subsite-based analysis. We these studies, in our study data the incidence of DM was came across multiple studies on detection rates of CT scans around 6% while there was no SPTs. A study by Nagarkar for SPT and DM. A study by Ong et al. where significant et al. reported findings similar to ours, with the incidence of emphasis to detect SPT and DM was given on the CT chest DM being 3.2% while not picking up SPTs [8]. Advanced T in initial screening involved around 47% of patients with and N stages were found to significantly correlate with the laryngeal malignancies while only 28% of patients belong rate of pickup of DMs. This is also echoed in the NCCN to the oral subset [4]. guidelines that mention CT thorax as a metastatic work-up in Table 3 Cost benefit analysis CECT thorax Chest X-ray ICER of CECT thorax vs chest X-ray Cost per Yield (Y ) Cost per Yield (Y ) (C – C )/(Y – Y ) T X T x T X patient (C ) patient (C ) T x All patients Rs 7000 0.06 Rs 200 0 Rs 113,333 cTumor stage   T1/2 Rs 7000 0.03 Rs 200 0 Rs 226,666   T3/4 Rs 7000 0.07 Rs 200 0 Rs 97,142 cNodal stage   N0/1 Rs 7000 0.04 Rs 200 0 Rs 170,000   N2/3 Rs 7000 0.07 Rs 200 0 Rs 97,142 Site of primary   Oral cavity and lip Rs 7000 0.04 Rs 200 0 Rs 170,000   Oropharynx Rs 7000 0.14 Rs 200 0 Rs 48,571   Larynx Rs 7000 0.22 Rs 200 0 Rs 30,909   Hypopharynx Rs 7000 0.03 Rs 200 0 Rs 226,666   Paranasal sinus Rs 7000 0.20 Rs 200 0 Rs 34,000 1 3 Indian Journal of Surgical Oncology higher T and N stages [3]. We noted a significant association patients. And only 2 of them smoked 30 pack years. This between cT stages and subsite of the primary tumor, while could explain why we did not find any second primaries N status failed to correlate significantly. These discrepancies in our study. warrant the need for reassessing the need for CT thorax as On cost effectiveness analysis, the ICER was most a routine distant metastatic workup for all HNSCC patients. efficient for subsites like larynx, oropharynx, and parana- The incidence of DM in head and neck cancers is rela- sal sinuses and for locoregionally advanced disease. Our tively small compared with other malignancies like stomach, analysis showed that the ICER of performing CT scan pancreas, lung, or breast [7]. This range of variation in the across all comers was a hefty 133,000 Indian rupees. With incidence of DM can possibly be explained by the fact that increasing cost of health care services, every screening all these studies have different numbers of populations of procedure must be justified not only based on sensitivity primary index tumors. but cost efficiency as well. Interestingly, in our study as well as in the aforemen- Luke Tan et al. published a study to evaluate the benefit tioned studies, the larynx was a common site associated with of CT chest as a screening tool in patients with HNSCC. increased risk of DM and SPT as compared to oral cavity A total of 20 patients were included in the study, and they subsites. If this associated difference was because of any concluded that even after adding an additional cost of particular habit history or any other risk factor was beyond $13,314, CT chest did not add to the extra sensitivity for the scope of our study. detecting DM and SPT [13]. NCCN guidelines recommend CT scan in locoregionally Although the efficiency and sensitivity of CT chest for advanced HNSCC . However, part of the justification for detecting DM and SPT are proven and have been included this recommendation has been the claim that CT also has in internationally accepted guidelines, the blanket use the additional advantage of picking SPTs, but on careful of CT chest for all HNSCC patients is not cost-effective evaluation of the literature, we found that the incidence of as per our experience. We found a statistically signifi- SPT was low at 1.5% in the study by Fukuhara et al. [5] and cant correlation in terms of ICER between DM and cT4 5.7% among 1086 patients in a study by Shah et al. [9]. Even oral disease with a value of 170,000/−, for oropharynx in an extensive literature review by Warren and Gates, where and hypopharynx 48,571/− and 226,666/− respectively, a total of 1259 cases were studied in detail, a total incidence for larynx 30,909/− and for paranasal sinuses 34,000/−. of 3.5% of SPT was noted. In our data of 281 patients, we Another factor that had a favorable ICER in our study was did not find even a single case of SPT, thereby questioning a nodal disease, i.e., N0/N1 disease vs N2/N3 disease, but the claim that CT thorax has the added advantage of picking this difference was statistically insignificant. up SPTs [10]. We did a cost analysis based on our findings and calcu- lated the ICER, which showed differences in cost-effective - ness based on subsites. This difference was most pronounced Conclusion in the oral cavity subsite and early-stage tumor and for N0/ N1 stage disease. The superiority of a CT chest over a con- In developing countries with limited resources and a high ventional X-ray has been established beyond doubt and this burden of disease, it is the need of the hour to cut down is reflected in the NCCN guidelines where preoperative CT on non-cost-effective diagnostic modalities. Although our chest has been advised during initial workup to look for DM, study design and findings are not robust enough to make SPT, and mediastinal lymphadenopathy [3]. However, in a rigid recommendations, they do suggest that there is a country like ours, there is a need to justify the additional scope to make CT thorax as a diagnostic modality more financial burden this approach entails. Our study data and cost-effective. CT thorax can be used in locally advanced results reflect a way that can be used for modifying existing HNSCC as a part of staging workup; however, our cost guidelines. The majority of the patient population in our analysis has not supported use in all the stages and all study comprised of the oral cavity subsite, which contrib- subsites. The need of the hour is to design larger, prefer- uted to only around 3.6% of the total detected DMs, while ably prospective studies so that we can identify the subsets laryngeal cancers contributed to 22% of the total detected that benefit most from CT scan as a screening modality for DMs. Interestingly, all the patients in oral cavity subsites metastases and avoid them in the rest, thereby decreasing who had metastatic deposits (4 patients) belong to locore- the financial burden on the healthcare and also decreasing gionally advanced stages. the deleterious effects of radiation exposure. The NLST trial showed the benefit of CT scan screen- ing in people with a high risk of lung cancer (one of their Author Contribution Conceptualization: Dr Nawaz Usman and Dr inclusion criteria was cigarette smoking for 30 pack years) Preethi S Shetty; methodology: Dr Punit S Dikhit and Dr Diksha [11, 12]. We only had smoking as a habit in 16.5% of our 1 3 Indian Journal of Surgical Oncology Dinker; formal analysis and investigation: Dr Punit S Dikhit and Dr 2. Hsu Y, Chu P, Liu J, Lan M, Chang S, Tsai T et al (2008) Role Naveena AN Kumar; writing—original draft preparation: Dr Naveena of chest computed tomography in head and neck cancer. Arch AN Kumar, Dr Punit S Dikhit, and Dr Akhil Palod; writing—review Otolaryngol-Head Neck Surg 134(10):1050 and editing: Dr Prakashini K and Dr Priya P Sankaran; Resources: Dr 3. National Comprehensive Cancer Network. Head and Neck Can- Somu G; Supervision: Dr Nawaz Usman and Dr Naveena Kumar AN. cers (Version 2.2022 — April 26, 2022). https:// www. nccn. org/ profe ssion als/ physi cian_ gls/ pdf/ head- and- neck. pdf. Accessed 1 June 2022 Funding Open access funding provided by Manipal Academy of 4. Ong T, Kerawala C, Martin I, Stafford F (1999) The role of thorax Higher Education, Manipal imaging in staging head and neck squamous cell carcinoma. J Cranio-Maxillofac Surg 27(6):339–344 Declarations 5. Fukuhara T, Fujiwara K, Fujii T, Takeda K, Matsuda E, Hasegawa K et al (2015) Usefulness of chest CT scan for head and neck Ethics Approval All human and animal studies have been approved by cancer. Auris Nasus Larynx 42(1):49–52 the appropriate ethics committee/institutional review board (IRB) of 6. Ferlito A, Shaha A, Silver C, Rinaldo A, Mondin V (2001) Inci- the KMC ethical committee board and have therefore been performed dence and sites of distant metastases from head and neck cancer. in accordance with the ethical standards laid down in the 1964 Dec- ORL. 63(4):202–207 laration of Helsinki and its later amendments, along with the ethics 7. Garavello W, Ciardo A, Spreafico R, Gaini R (2006) Risk factors committee. for distant metastases in head and neck squamous cell carcinoma. Arch Otolaryngol-Head Neck Surg 132(7):762 Consent for Publication Written informed consent for publication of 8. Raj VN, Ashvin PW, Gauri SK, Mayank P, Aditya MM (2017) their clinical details was obtained from the patient. Incidence and Prognostic Factors in Distant Metastasis from Pri- mary Head and Neck Cancer-An Institutional Experience. J Head Neck Spine Surg 1(5):555571 Conflict of Interest The authors declare no competing interests. 9. Shah S, Applebaum E (2000) Lung cancer after head and neck can- cer: role of chest radiography. Laryngoscope 110(12):2033–2036 Open Access This article is licensed under a Creative Commons Attri- 10. Warren S, Gates O (1932) Multiple primary malignant tumors: bution 4.0 International License, which permits use, sharing, adapta- a survey of the literature and a statistical study. Am J Cancer tion, distribution and reproduction in any medium or format, as long 16:1358–414 as you give appropriate credit to the original author(s) and the source, 11. The National Lung Screening Trial (2011) overview and study provide a link to the Creative Commons licence, and indicate if changes design. Radiology 258(1):243–253 were made. The images or other third party material in this article are 12. National Lung Screening Trial Research Team, Church TR, included in the article's Creative Commons licence, unless indicated Black WC, Aberle DR, Berg CD, Clingan KL, Duan F, Fager- otherwise in a credit line to the material. If material is not included in strom RM, Gareen IF, Gierada DS, Jones GC, Mahon I, Marcus the article's Creative Commons licence and your intended use is not PM, Sicks JD, Jain A, Baum S (2013) Results of initial low-dose permitted by statutory regulation or exceeds the permitted use, you will computed tomographic screening for lung cancer. N Engl J Med need to obtain permission directly from the copyright holder. To view a 368(21):1980–1991 copy of this licence, visit http://cr eativ ecommons. or g/licen ses/ b y/4.0/ . 13. Tan L, Greener C, Seikaly H, Rassekh C, Calhoun K (1999) Role of screening chest computed tomography in patients with advanced head and neck cancer. Otolaryngol-Head Neck Surg 120(5):689–692 References Publisher's Note Springer Nature remains neutral with regard to 1. Reiner B, Siegel E, Sawyer R, Brocato R, Maroney M, Hooper F jurisdictional claims in published maps and institutional affiliations. (1997) The impact of routine CT of the chest on the diagnosis and management of newly diagnosed squamous cell carcinoma of the head and neck. Am J Roentgenol 169(3):667–671 1 3

Journal

Indian Journal of Surgical OncologySpringer Journals

Published: Aug 4, 2022

Keywords: CT thorax; Distant metastatic workup; CT scan; Computed tomography; Second primary tumor; Cost effectiveness

References