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The Characteristics and Survival of Second Primary Lung Cancer After Hodgkin’s Lymphoma: A Comparison With First Primary Lung Cancer Using the Seer Database

Ling Lin, Daquan Wang, Haizhu Chen

Abstract

Objective

The study aimed to compare the characteristics and prognosis between patients with second primary lung cancer following Hodgkin’s lymphoma and those with primary lung cancer.

Materials and methods

Using the SEER 18 database, the characteristics and prognosis were compared between the second primary non-small cell lung cancer following Hodgkin’s lymphoma (HL-NSCLC) (n = 466) and the first primary non-small cell lung cancer (n = 469,851)(NSCLC-1), as well as between the second primary small cell lung cancer following Hodgkin’s lymphoma (n = 93) (HL-SCLC) and the first primary small cell lung cancer (n = 94,168) (SCLC-1). Comparisons of categorical variables were performed using Chi-square or Fisher’s test. Continuous variables were compared using the Mann-Whitney U test. Overall survival (OS) was estimated using the Kaplan-Meier method, and the difference between groups was analyzed by log-rank test.

Introduction

Hodgkin’s lymphoma (HL) can be diagnosed at any age and it is most common in young adults [1]. Over the past decades, the remarkable progress in the treatment of HL has greatly improved survival outcomes, which makes HL one of the most curable cancers [2, 3]. With the combination of multi-agent chemotherapy and radiotherapy, the overall survival (OS) rates at 5 and 10 years for HL are 86% and 80%, respectively [1]. However, the prolonged survival following effective HL treatment has been accompanied by increased risk of subsequent malignancies, cardiovascular disease or other late effects [4–7]. According to the cancer databases from North America and Europe, approximately 6.6% to 12% of HL survivors developed second primary cancers during further follow-up, and lung cancer (LC) accounted for the most frequent type of solid tumors [6, 8–10]. A study from Sweden reported 2.39-fold increased risk of developing a second cancer among HL survivors, with a 3.3-fold increased risk of developing second lung cancer [9]. Lung cancer accounted for a large proportion of late deaths among HL survivors [11].

Materials and methods

Study population

The SEER 18 Program database (Case Listing and Frequency Sessions: Incidence-SEER 18 Research Data + Hurricane Katrina Impacted Louisiana Cases, November 2018 Sub (1975–2016 varying)) (https://seer.cancer.gov/data-software/documentation/seerstat/nov2018) was used for patient collection in this study. This database contained the data of patients diagnosed between 1975 and 2016. Tumor histology was classified with the third edition of the International Classification of Diseases for Oncology (ICD-O-3). This study was approved by the Ethics Committee of National Cancer Institute (SEER Program), with an approval number of SAR0040750. This observational study used de-identified and publicly available data from SEER and thus did not require formal consent from patients.

Fig 1 showed the case selection diagram. Firstly, the ICD-O-3 histology codes of HL were used to select HL patients, including nodular sclerosis (9663, 9664, 9665, 9667), classical Hodgkin lymphoma (9650), lymphocyte-rich (9651), mixed cellularity (9652), lymphocyte-depleted (9653, 9655) and nodular lymphocyte predominant (9659). A total of 58208 patients with HL were identified after the first step. Secondly, the variable of “Sequence number” was collected for these HL patients, and only the patients with “Sequence number” of “1st of 2 or more primaries” were included. A total of 5881 patients who developed subsequent cancer following the first primary HL were identified after the second step.

Results

Patient characteristics at time of HL diagnosis

A total of 466 HL survivors developed NSCLC following HL, with a median latency of 10.3 years (range, 0.2–39.7 years), and 93 survivors developed SCLC following HL, with a median latency of 9.8 years (range, 0.34–35.1 years). Table 1 shows patient characteristics at time of HL diagnosis according to subsequent lung cancer stage. Patients with shorter latency from HL to lung cancer had earlier lung cancer stage, and the median latencies were 7, 10.1 and 15 years for localized, regional and distant stage groups, respectively(P<0.001). The age of patients at HL diagnosis was significantly different between the three stage groups, with median age of 55, 52 and 43 years for localized, regional and distant stage groups, respectively (P<0.001). Additionally, the HL patients diagnosed in 2000–2016 had earlier stage of lung cancer than those diagnosed in 1975–1999 (P = 0.002). In contrast, among the three stage groups for HL-SCLC, the distributions of latency, age, year at HL diagnosis and HL chemotherapy were similar.

Discussion

Due to the rarity of HL-LC, it is difficult to thoroughly investigate this disease entity in large series. Until now, few studies have reported the characteristics and outcomes of HL-LC. In this large population-based study, we performed a direct comparison of the characteristics and survival between the HL-LC group and the LC-1 group. The survival outcomes of HL-SCLC were described for the first time. We demonstrated that HL-NSCLC patients had an inferior OS compared with NSCLC-1 patients (P = 0.006), whereas no significant difference in OS was observed between HL-SCLC patients and SCLC-1 patients (P = 0.390). Besides, this study explored the prognostic factors affecting OS for HL-NSCLC and HL-SCLC, which might provide guidance for monitoring and treating these patients.

Conclusion

In conclusion, patients who developed second primary lung cancer after Hodgkin’s lymphoma had worse prognosis than those with primary lung cancer. The percentage of deaths from lung cancer in the HL-NSCLC group was lower than that in the NSCLC-1 group. However, patients with HL-SCLC patients shared similar characteristics and survival outcomes with SCLC-1 patients. Further studies are warranted to elucidate the molecular biology of HL-LC patients.

Citation: Lin L, Wang D, Chen H (2023) The characteristics and survival of second primary lung cancer after Hodgkin’s lymphoma: A comparison with first primary lung cancer using the SEER database. PLoS ONE 18(5): e0285766. https://doi.org/10.1371/journal.pone.0285766

Editor: Wen-Wei Sung, Chung Shan Medical University, TAIWAN

Received: September 6, 2022; Accepted: April 29, 2023; Published: May 17, 2023

Copyright: © 2023 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: This study’s data cannot be shared publicly by the authors because it is from Surveillance, Epidemiology, and End Results (SEER) databases. The data set is publicly available via the NCI’s SEER program upon signing a Data Use Agreement with the NCI (https://seer.cancer.gov/data/access.html). Anyone who want to access SEER data must sign this agreement and gain approval from NCI. Request forms may be accessed at https://seer.cancer.gov/seertrack/data/request. The authors did not have any special access privileges beyond that of others who follow this NCI access process. Any interested researchers can replicate our study by directly obtaining the data from the SEER database and following the protocol in our Methods section after gaining access.

Funding: The authors received no specific funding for this work.

Competing interests: The authors have declared that no competing interests exist.

Abbreviations: CI, confidential interval; CT, computed tomography; HL, Hodgkin’s lymphoma; HL-LC, the second primary lung cancer following Hodgkin’s lymphoma; HL-NSCLC, the second primary non-small cell lung cancer following Hodgkin’s lymphoma; HL-SCLC, the second primary small cell lung cancer following Hodgkin’s lymphoma; HR, hazard ratio; ICD-O-3, the third edition of the International Classification of Diseases for Oncology; LC, lung cancer; LC-1, the first primary lung cancer; NHL, non-Hodgkin’s lymphoma; NSCLC, non-small cell lung cancer; NSCLC-1, the first primary non-small cell lung cancer; OS, overall survival; SCC, squamous cell carcinoma; SCLC, small cell lung cancer; SCLC-1, the first primary small cell lung cancer; SEER, Surveillance, Epidemiology, and End Results

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0285766#sec019

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