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Original ResearchFree Access

Use of Preoperative FDG PET/CT and Survival of Patients with Resectable Non–Small Cell Lung Cancer

Published Online:Jun 21 2022https://doi.org/10.1148/radiol.212798

Abstract

Background

The added value of preoperative PET/CT for the overall survival of patients with resectable non–small cell lung cancer (NSCLC) is unknown.

Purpose

To investigate the association of the use of preoperative PET/CT on survival of patients with resectable stage I–IIIB NSCLC.

Materials and Methods

In this retrospective study, patients with resectable stage I–IIIB NSCLC who underwent thoracic surgery from January 1, 2009, to December 31, 2018, from the Taiwan Cancer Registry were included. The last follow-up date was December 31, 2019. Patients were categorized into two groups according to whether they underwent preoperative metabolic imaging with fluorine 18 fluorodeoxyglucose PET/CT. Patients who did not undergo preoperative imaging were used as the control group. The primary outcome of interest was all-cause mortality. Patients in both groups were propensity score matched at a ratio of 1:1. Matching variables used were sex, age, histologic findings, American Joint Committee on Cancer clinical stage, cT stage, cN stage, current and past smoker history, adjuvant chemotherapy, adjuvant chemoradiation, Charlson comorbidity index, and hospital type. Survival curves were generated using the Kaplan-Meier method and compared using the log-rank test.

Results

In the matched cohort, 6754 patients (3349 men, mean age ± SD: 64 years ± 11) underwent PET/CT and 6754 did not (3362 men, mean age: 64 years ± 11). In adjusted analysis, patients with stage IIIA or IIIB NSCLC and preoperative PET/CT had a lower risk of death versus those without PET/CT (for stage IIIA: hazard ratio [HR] = 0.90 [95% CI: 0.79, 0.94], P = .02; for stage IIIB: HR = 0.80 [95% CI: 0.71, 0.90], P < .01). There was no improvement in a lower risk of death for patients with stage I–II NSCLC (after multivariable adjustment, the HR was 1.19 [95% CI: 0.89, 1.30], P = .65).

Conclusion

Use of preoperative PET/CT was associated with lower risk of death in patients with stage IIIA–IIIB non–small cell lung cancer compared with those without preoperative PET/CT.

© RSNA, 2022

Online supplemental material is available for this article.

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Summary

Use of preoperative PET/CT was associated with lower risk of death in patients with stage IIIA–IIIB non–small cell lung cancer.

Key Results

  • ■ In 6754 propensity score–matched patients with non–small cell lung cancer (NSCLC), use of preoperative fluorodeoxyglucose (FDG) PET/CT was associated with a lower risk of death in patients with stage IIIA–IIIB NSCLC compared with those without PET/CT (hazard ratio [HR]: 0.90, P = .02).

  • ■ Use of preoperative FDG PET/CT was not associated with a lower risk of all-cause mortality in patients with stage I–II NSCLC (HR: 1.19, P = .65).

Introduction

Metabolic imaging with fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT has high sensitivity and specificity for helping diagnose lung cancer with distant metastases, including bone metastases (1). PET/CT is increasingly being used for the clinical staging and evaluation of possible metastatic disease, including osseous metastasis from lung cancer, and PET/CT is extensively used for pretreatment evaluation according to the National Comprehensive Cancer Network clinical practice guidelines (2–4). For lung cancer, although PET/CT is possibly less sensitive (especially for osteoblastic foci) and more expensive, it is more specific than bone scans for helping detect bone metastases (2,3).

A major benefit of 18F-FDG PET/CT over bone scans is its ability to screen for distant metastases at sites other than bone (5,6). Hence, consensus-based National Comprehensive Cancer Network guidelines recommend the use of integrated PET/CT to evaluate distant metastases at all sites, including bone, in patients newly diagnosed with non–small cell lung cancer (NSCLC) and small cell lung cancer (4). On the basis of National Comprehensive Cancer Network guidelines between 2009 and 2018 (7), initial surgery followed by adjuvant treatment, rather than chemotherapy or chemoradiotherapy alone, is recommended for patients with clinical stage I–II disease. Stage III NSCLC includes a highly heterogeneous group of patients with differences in the extent and location of disease. According to the American Joint Committee on Cancer (AJCC), 8th edition, surgery or concurrent chemoradiotherapy is recommended for cN2 disease, but not multistation N2 disease, in stage III NSCLC chemoradiotherapy. In Taiwan, some surgeons still choose surgery for cN2 NSCLC. Therefore, in Taiwan, patients with stage III N2 NSCLC have a choice of radiation therapy or surgery for their treatment options. Specifically, patients with stage IIIB (cT3–4, cN2) NSCLC may receive treatment using either thoracic surgery or chemoradiotherapy, which is not the standard of care in the United States.

Despite the widespread use of whole-body PET/CT as a routine staging tool, its value is not universally recognized (8–10). Although whole-body PET/CT is more accurate than CT for detecting occult disease, a randomized trial that included a small sample size and a short follow-up period reported that its use did not improve survival (8). Moreover, evidence regarding whether PET/CT can reduce the risk of futile thoracotomy is conflicting (8–10). Thus, PET/CT should be considered as a staging modality for the diagnosis of occult disease, although PET/CT does not increase survival in NSCLC; however, studies on this topic that have included an adequate sample size and follow-up period are lacking.

The value of routine PET/CT use in the evaluation of resectable NSCLC remains controversial. There are no large randomized controlled trials demonstrating that routine use of PET/CT improves survival or reduces the rate of NSCLC. The purpose of this study was to conduct a propensity score–matched study to investigate the use of preoperative PET/CT in relationship to survival for patients with resectable NSCLC.

Materials and Methods

Study Design and Patient Data Source

This retrospective study was conducted using data from the Health and Welfare Data Center established by Taiwan’s Ministry of Health and Welfare. The Health and Welfare Data Center consolidates data gathered by the Taiwanese government from various sources. These data are then deidentified and made available for research purposes based on case-by-case approval. In particular, we used the Taiwan Cancer Registry, which includes the detailed staging and treatment information of patients with cancer, the Cause of Death database, which lists all death certificates issued in Taiwan (11), and the National Health Insurance Research Database, which contains billing information on all National Health Insurance–reimbursed examinations, medications, and treatments. We are confident the finding “no evidence of death” is equivalent to “evidence of life” because all death certificates are issued by this governmental system and are required for property inheritance, abandonment of inheritance to the court, and burial in Taiwan and/or cremation. The National Health Insurance program has been implemented since 1995 and covers more than 99% of Taiwan’s population. Since July 2004, the National Health Insurance has been reimbursing the cost of 18F-FDG PET examinations performed for the initial staging of lung cancer when optimal staging is not achieved through conventional CT. All databases in the Health and Welfare Data Center are linked through a common but anonymized identifier to ensure privacy. The requirement for informed consent was waived due to the retrospective and deidentified nature of this study.

The study protocols were reviewed and approved by the institutional review board of Tzu-Chi Medical Foundation (IRB109–015-B).

Study Sample

We consecutively selected patients aged at least 20 years who underwent thoracic surgical resection of pathologically proven NSCLC between January 1, 2009, and December 31, 2018. The study flowchart is presented as Figure 1.

Study flowchart of patients newly diagnosed with non–small cell lung cancer (NSCLC) between 2009 and 2018.

Figure 1: Study flowchart of patients newly diagnosed with non–small cell lung cancer (NSCLC) between 2009 and 2018.

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Covariates and Outcome Definition

We extracted data regarding sex, age, histologic findings, AJCC clinical stage, cT stage, cN stage, smoking history, adjuvant chemotherapy, adjuvant chemoradiation, Charlson comorbidity index (CCI), hospital type (medical center or nonmedical center), and disease status at the last follow-up date from the Taiwan Cancer Registry. Clinical stages were based on the AJCC 8th edition for NSCLC. Age was analyzed as a continuous variable. We selected patients with squamous cell carcinoma, adenocarcinoma, or others (large cell carcinoma, adenosquamous carcinoma, sarcomatoid carcinoma, and carcinoid tumor). All patients with nonmetastatic resectable NSCLC underwent thoracic surgery and adjuvant treatments, such as adjuvant chemotherapy and chemoradiation, based on National Comprehensive Cancer Network guidelines (4). Resectability was verified by the professional thoracic surgeons, and thoracic surgery was performed for all patients in our study. The index date was the date of thoracic surgery. Thoracic surgery procedures included in this study were lobectomy, segmentectomy, wedge resection, and pneumonectomy. Patients underwent lymphadenectomy per clinical routine as needed.

From the National Health Insurance Research Database, we identified patients who underwent 18F-FDG PET/CT examinations within 0–90 days before the index date (thoracic surgery). Patients with a record of 18F-FDG PET/CT were considered to have undergone preoperative PET/CT, whereas those without records were considered to have not undergone preoperative PET/CT. For the non-PET group, clinical stages were determined with CT, contrast-enhanced brain MRI, and bronchoscopy. For the PET group, staging was determined with chest-abdomen-pelvis CT, contrast-enhanced brain MRI, bronchoscopy, and PET/CT. The professional nuclear medicine physicians and radiologists who are licensed in Taiwan officially interpreted and reported all the images. The Taiwan Cancer Registry Database requires that all PET/CT reports are reviewed and reported by trained nuclear medicine physicians. Moreover, the Taiwan Cancer Registry Administration randomly reviews reports of images by means of peer review to verify the accuracy of diagnoses, and hospitals with outlier charges or practices may be audited and subsequently be heavily penalized if malpractice or discrepancies are identified. The primary outcome of interest was all-cause mortality, which was calculated from the initial date to the date of death. Information on overall survival was obtained from the Cause of Death database. Patients whose death records could not be found were considered alive and censored on the last day of the database record (December 31, 2019).

Propensity Score Matching

After adjusting for confounders, an author (S.Y.W., with 11 years of experience) used a Cox proportional hazards model to model time from the index date to all-cause mortality for patients with NSCLC who underwent thoracic surgery. We used a propensity score–matching design to reduce confounding factors and to estimate the preoperative PET/CT directionality of the possible survival correlation. Matching variables used were sex, age, histologic findings, AJCC clinical stage, cT stage, cN stage, smoker history, adjuvant chemotherapy, adjuvant chemoradiation, CCI, and hospital type (medical or nonmedical center). However, a residual imbalance was still noted in some covariates, such as cT stage, cN stage, and current smoker status (12). Comorbidities for CCI calculation were determined according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes in the main diagnosis of inpatient records or those in outpatient records if the number of outpatient visits was at least two within 1 year. Comorbidities with onset 12 months before the index date were recorded. We matched the cohorts at a ratio of 1:1 by using the greedy method, and covariates were matched with a propensity score within a caliper of .2 (13).

Medical Center versus Nonmedical Center Treatment

In Taiwan, medical centers have dedicated thoracic oncology treatment teams of radiologists, oncologists, radiation therapists, and thoracic surgeons, while not all nonmedical centers have these.

Statistical Analysis

Continuous data are presented as means ± SDs or medians and IQRs, as applicable, whereas categorical data are presented as numbers and percentages. The distribution of patient characteristics was compared using the χ2 test for categorical variables and the two-tailed Student t test or Kruskal-Wallis test for continuous variables.

Survival curves were generated using the Kaplan-Meier method and compared using the log-rank test. The adjusted Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% CI and to estimate the correlation of covariates on overall survival. We examined the interaction effect by adding clinical stages multiplied by predictor in univariable and multivariable models via PROC PHREG (SAS, version 9.4) and estimated crude HR stratified by clinical stages. The martingale residuals show little skewed results, but there is no distinguishable observation in the residual plots. For the supremum test, P = .0530 for proportion hazards assumption. Our models have evidence for multicollinearity, model saturation, and possible evidence of the violation of the proportional hazards assumption. We determined the interaction effect between clinical stages and the use of preoperative PET scan (Table E1 [online]) and analyses by clinical stage. Stratified analysis to determine the effect of preoperative PET/CT on various AJCC clinical stages (II, IIIA, and IIIB) was performed to investigate the association of preoperative PET/CT on overall survival across various subgroups. Sample size of different AJCC stages is shown in Table 1. All statistical analyses were performed using SAS (version 9.4; SAS Institute). A two-sided P < .05 was considered to indicate a statistically significant difference.

Table 1: Demographic Characteristics of Patients with Resectable NSCLC Who Underwent or Did Not Undergo Preoperative PET/CT before Thoracic Surgery (after Propensity Score Matching)

Table 1:

Results

Patient Characteristics

A total of 19 439 patients met the inclusion criteria before propensity score matching (Table 1). After propensity score matching, a final cohort of patients underwent preoperative PET/CT (6754 patients [3349 men and 3405 women], mean age: 64 years ± 11) and those who did not (6754 patients [3362 men and 3405 women], mean age: 64 years ± 11). A total of 6754 patients with NSCLC who underwent thoracic surgery were included in both the case and control groups (Fig 1). Most of the covariates were balanced between the case and control groups, but more patients had advanced cT stages, advanced cN stages, and a history of smoking in the preoperative PET/CT group than in the non–preoperative FDG PET/CT group. All covariates had absolute standardized mean difference less than .1 (Table 1), and data balance was achieved after propensity score matching (14). The median follow-up periods of the preoperative PET/CT and non–preoperative FDG PET/CT groups were 61 and 60 months, respectively.

Predictors of Survival

The findings of univariable and multivariable analyses did not reveal an association between preoperative PET/CT and improved survival (in the adjusted model, the HR was 0.92 [95% CI: 0.86, 1.09; P = .51]) (Table 2). Known prognostic factors, namely, male sex (P < .01), age greater than 60 years (P < .01), advanced cT (P < .01) and cN (P < .01) stage, current and past smoker status (P < .01), CCI of at least 1 (P < .01), and treatment at a nonmedical center (P < .01), were associated with poor overall survival in univariable analysis. In multivariable analysis, after adjustment for covariates, sex, age, histologic findings, AJCC clinical stage, cT and cN stages, smoking habits, adjuvant chemotherapy, adjuvant chemoradiation, CCI, and hospital type remained independently associated with poor overall survival.

Table 2: Cox Proportional Hazards Regression Analysis of the Risk of All-Cause Mortality among Propensity Score–matched Patients with Resectable NSCLC Who Underwent or Did Not Undergo Preoperative PET/CT before Thoracic Surgery

Table 2:

Stratified Analysis of the Effect of Preoperative PET/CT

We performed stratified analysis to determine the effect of preoperative PET/CT on various AJCC clinical stages. We stratified the AJCC clinical stages (I–II, IIIA, and IIIB) by using a Cox regression model and adjusted for sex, age, histologic findings, AJCC clinical stage, cT and cN stages, current smoker status, adjuvant chemotherapy, adjuvant chemoradiation, CCI, and hospital type (Table 3). The largest correlation between preoperative PET/CT and all-cause mortality was observed in patients with stage IIIB NSCLC undergoing thoracic surgery (after multivariable adjustment, the HR was 0.80 [95% CI: 0.71, 0.90]; P < .01), followed by patients with stage IIIA NSCLC receiving thoracic surgery (in the adjusted model, the HR was 0.90 [95% CI: 0.79, 0.94]; P = .02). Among the patients in the preoperative and non–preoperative FDG PET/CT groups, the 5-year overall survival was 57.1% and 54.5%, respectively, for those with stage IIIA disease (P = .03) and 50.4% and 41.4% for those with stage IIIB disease (P < .01) (Fig 2). Among the patients with early-stage (I–II) NSCLC receiving thoracic surgery, we found no evidence of an association between the case and control groups for overall survival (after multivariable adjustment, the HR was 1.19 [95% CI: 0.89, 1.30]; P = .65).

Table 3: Cox Proportional Hazards Regression Analysis of the Risk of All-Cause Mortality among Propensity Score–matched Patients with Resectable NSCLC Who Underwent or Did Not Undergo Preoperative PET/CT before Thoracic Surgery, Stratified by Clinical Stage

Table 3:
Kaplan-Meier curves show overall survival for propensity score–matched patients with (A) clinical stage I–II and (B) clinical stage IIIA resectable non–small cell lung cancer (NSCLC) who underwent or did not undergo preoperative PET/CT before thoracic surgery. (C) Kaplan-Meier curves show overall survival for propensity score–matched patients with clinical stage IIIB NSCLC.

Figure 2: Kaplan-Meier curves show overall survival for propensity score–matched patients with (A) clinical stage I–II and (B) clinical stage IIIA resectable non–small cell lung cancer (NSCLC) who underwent or did not undergo preoperative PET/CT before thoracic surgery. (C) Kaplan-Meier curves show overall survival for propensity score–matched patients with clinical stage IIIB NSCLC.

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We noted progressively increasing rates of PET/CT utilization for staging in later years: 5% in 2009–2011, 27% in 2012–2014, and 42% in 2015–2018. However, the association between the utilization of PET for staging and the survival of patients with stage IIIA–IIIB disease remained relatively unchanged: 0.84 in 2009–2011, 0.84 in 2012–2014, and 0.85 in 2015–2018 (data not shown). Furthermore, we found no evidence of an association between the case and control groups for overall survival of patients with stage I–II disease as a function of time: 1.07 in 2009–2011 (P = .81), 1.14 in 2012–2014 (P = .79), and 1.15 in 2015–2018 (P = .64).

Change of Stage

Table E2 (online) shows the change of stage (the consistency between clinical stages and pathologic stages) for patients with thoracic surgery. The more consistent clinical and pathologic stages for clinical stage IIIA–IIIB in the PET group represent more accurate stages for advanced clinical stages than the non-PET group.

Interaction Effect between Clinical Stages and PET Scan

There is significant interaction effect between clinical stages and preoperative PET/CT (Table E1 [online]), and the analyses stratified by clinical stage was indispensable.

Discussion

The indication for the use of fluorodeoxyglucose (FDG) PET/CT as a staging tool is commonplace, but large-scale randomized controlled trials evaluating whether routine FDG PET/CT can improve survival or reduce the need for thoracotomy are lacking. We conducted a propensity score–matching study to investigate the use of preoperative PET/CT on the survival of patients with resectable non–small cell lung cancer (NCSLC) at different clinical stages. We attempted to clarify the indications for the optimal use of preoperative PET/CT in patients with resectable NSCLC based on American Joint Committee on Cancer 8th edition clinical staging. Preoperative PET/CT was associated with a lower risk of death in patients with stage IIIA–IIIB NSCLC (for stage IIIA: adjusted hazard ratio [HR] = 0.90 [95% CI: 0.79, 0.94], P = .02; for stage IIIB: adjusted HR = 0.80 [95% CI: 0.71, 0.90], P < .01) but not in patients with stage I–II NSCLC (adjusted HR: 1.19 [95% CI: 0.89, 1.30]; P = .65). Better survival was noted in tertiary medical centers; hospital status (medical centers or nonmedical centers) was the most important selection bias in the use of PET/CT due to lack of PET/CT facilities at nonmedical centers in Taiwan.

Prior randomized clinical trials with smaller sample sizes have suggested that the use of PET/CT reduced the number of futile thoracotomies, although PET/CT did not improve survival (8,9). Our findings indicated that preoperative PET/CT did not improve survival in our propensity score–matched population with resectable NSCLC (for all clinical stages, including stage I–IIIB in the adjusted model, the HR was 0.92 [95% CI: 0.86, 1.09]; P = .51); this result is in agreement with those of previous studies (8,9). This finding can be attributed to the relatively low sensitivity and specificity of PET, which can result in false-negative results and miss occult cancer, especially in patients with early-stage NSCLC (15), thus leading to false-positive results or missed opportunities for potentially curative thoracotomy (8,16).

The longer overall survival of the patients with stage IIIA–IIIB NSCLC in the preoperative PET/CT group can be attributed to a higher staging accuracy for advanced stages compared with those in the non–preoperative FDG PET/CT group. The recurrence-free survival in the PET/CT group is also superior to that in the non–PET/CT group (data not shown because the end point is overall survival). Our findings agree with those of previous studies (8,15,16). Whether PET/CT is useful for identifying occult metastasis in patients with clinical early-stage NSCLC who have a low risk of occult metastasis remains unclear (15). PET/CT can be beneficial for patients with clinical stage IIIA–IIIB disease with a high risk of occult stage IV disease (8,16).

In accordance with the findings of a previous study (16), our results indicate that PET/CT might be unnecessary in early clinical stages; either cervical mediastinoscopy or surgical resection of the primary tumor with mediastinal sampling at the time of surgery should be directly performed. Although PET/CT might be beneficial for patients with resectable advanced IIIA–IIIB NSCLC, PET/CT can further reduce the risk of unnecessary surgery; this finding is consistent with those of previous studies (8,16). On the basis of our results, preoperative PET/CT should be encouraged in patients with stage IIIA–IIIB NSCLC to reduce the risk of unnecessary surgery and more accurately stage advanced disease. A multidisciplinary approach is considered essential for the management of stage III disease (2–4). Some experts offer thoracic surgery in some selected patients (single-station N2 disease <3 cm) (17). It seems that the IIIB group had survival benefits with preoperative PET/CT because preoperative PET/CT can help identify the T3N2 group in those patients who can undergo resection versus those who should not undergo surgery but instead undergo definitive chemoradiotherapy, which is now followed by programmed cell death ligand-1. Moreover, we suggest excluding preoperative PET/CT in those with resectable stage I–II NSCLC because errors associated with PET/CT (eg, false-positive findings) can occur with benign FDG-avid lesions, such as those due to infections, inflammation, and granulomatous disease, resulting in missed opportunities for potentially curative thoracotomy (18).

Prior studies that have evaluated the association between preoperative PET scanning and therapeutic outcomes in NSCLC have reported conflicting results (8,9,19–21). Although two studies have indicated that the use of PET as a staging modality could reduce the rate of futile thoracotomies in this population (8,9), three studies have reported no difference in the same population (19–21). This conflict may be explained by specific details of the individual studies, including use of PET versus PET/CT and inclusion of patients with high-risk (advanced NSCLC [stage IIIA–IIIB] diagnosed with chest CT) versus low-risk (early-stage NSCLC [stage I–II] diagnosed with chest CT) metastatic disease (8,9,19–21). Small sample reports and case series have suggested that when PET/CT is used as a staging modality for NSCLC, unsuspected metastases are detected in 6%–36% of patients (22,23). In addition, their discovery can result in stage migration (upstage or downstage) and changes in the management of 19%–22% of patients (23–25). If preoperative PET/CT is performed in patients with stage I–II NSCLC, most of the cases that are upstaged based on PET/CT findings should be confirmed through tissue sampling to avoid missing the opportunity for a surgical cure (18). False-positive upstaging of early-stage NSCLC might be contributing to patients with early-stage NSCLC missing the opportunity for a surgical cure.

This study has several limitations. First, all patients with resectable NSCLC were enrolled from an Asian population in Taiwan. Treatment plans before and after PET/CT were not available. Propensity score matching cannot control for factors not accounted for in the model and is predicated on an explicit selection bias of those who could be matched (ie, those who could not be matched are not part of the scope of inference). In this retrospective analysis, resectability criteria likely vary by thoracic surgeons. Third, the reason for use of PET/CT is unclear in a retrospective analysis, which may lead to selection bias. Fourth, the effects of PET/CT might be underestimated because some of these patients were considered as the non–PET/CT controls, when in fact they may have undergone PET/CT and it was just not recorded. Finally, although differences between groups were statistically significant at P < .05, the overall effect size of the intervention (PET/CT) was small.

In conclusion, we showed a lower risk of death associated with the use of fluorine 18 (18F)–fluorodeoxyglucose (FDG) PET/CT for patients with stage IIIA and IIIB non–small cell lung cancer. The use of this examination allowed for better staging concordance between the clinical and final pathologic stage. We found no benefit for the use of 18F-FDG PET/CT in clinical stage I and II disease. A large randomized controlled trial would be necessary to confirm these findings.

Disclosures of conflicts of interest: W.M.C. No relevant relationships. M.C. No relevant relationships. J.G.H. No relevant relationships. T.S.L. No relevant relationships. B.C.S. No relevant relationships. S.Y.W. Member of Taiwan Radiological Society and Taiwan Society for Therapeutic Radiology and Oncology.

Author Contributions

Author contributions: Guarantors of integrity of entire study, J.G.H., T.S.L., B.C.S., S.Y.W.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; agrees to ensure any questions related to the work are appropriately resolved, all authors; literature research, W.M.C., J.G.H., S.Y.W.; clinical studies, W.M.C., B.C.S., S.Y.W.; statistical analysis, M.C., T.S.L., B.C.S., S.Y.W.; and manuscript editing, J.G.H., S.Y.W.

Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, supports work of S.Y.W. (Funding Numbers: 10908, 10909, 11001, 11002, 11003, 11006, and 11013).

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Article History

Received: Nov 5 2021
Revision requested: Dec 15 2021
Revision received: Mar 30 2022
Accepted: Apr 5 2022
Published online: June 21 2022
Published in print: Oct 2022