Why is Lung Cancer High in Non-Smoking Women?

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Why is Lung Cancer High in Non-Smoking Women?

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Why is Lung Cancer High in Non-Smoking Women? Two Key Screening Recommendations for Low-Risk Individuals!

When it comes to lung cancer, many people immediately associate it with smoking, and it’s likely that you’ve cautioned your smoking friends and family members about it.

However, surprisingly, non-smoking lung cancer is one of the top seven causes of cancer-related deaths globally.

This is particularly true in Asia, where about 60%-80% of female lung cancer patients have never smoked [1].

However, non-smoking Asian women are not typically considered a high-risk group for lung cancer screening.

Current lung cancer screening research and guidelines still mainly rely on age and smoking history, as seen in the U.S. National Lung Screening Trial (NLST), which targets high-risk individuals based on these factors [2].

Consequently, in the United States, low-dose chest CT (LDCT) screening is currently only offered to current or former smokers [3].

In China, according to the latest “Chinese Lung Cancer Low-Dose CT Screening Guidelines (2023 Edition),” non-smoking females are also not emphasized as a high-risk group [2].

The TALENT study, focused on non-smoking high-risk individuals in Taiwan, reported a lung cancer detection rate of 2.6%, significantly higher than the 1.1% reported in the NLST study [4,5]. So, what is the specific lung cancer detection rate among non-smoking Asian women?

Preliminary results of the FANSS study released,Lung cancer detection rate among Asian non-smoking women reaches 1.5%

Preliminary results from the FANSS study, announced at the 2023 World Conference on Lung Cancer (WCLC) held in Singapore from September 9 to 12, revealed a lung cancer detection rate of 1.5% among non-smoking Asian women [6].

FANSS is a prospective, multicenter study conducted in Taiwan, aiming to include 1,000 participants who are non-smoking Asian females aged 40-74 with no history of lung cancer or any cancer treatment within the past 5 years. After collective decision-making, participants undergo LDCT or plasma ctDNA testing. The main goal of the study is to establish a clinical, demographic, and radiological database for non-smoking Asian women receiving LDCT screening to assess the feasibility of lung cancer screening (Figure 1).

As of January 15, 2023, 221 participants have signed informed consent forms, with 201 of them receiving baseline LDCT examinations. The median age of participants is 56.6 years (range 40-74), with 89% coming from China. Among the participants, 47% are passive smokers, and 49% are non-passive smokers.

Among the 201 participants who completed LDCT, 43.3% had Lung-RADS 1, 49.8% had Lung-RADS 2, 3.0% had Lung-RADS 3, 1.5% had Lung-RADS 4A, and 2.0% had Lung-RADS 4B. Three patients were diagnosed with lung adenocarcinoma (2 in stage IIB and 1 in stage IIIC), resulting in a lung cancer detection rate of 1.5% (Figure 2). All patients underwent surgical resection, tested positive for EGFR mutations, and are currently receiving adjuvant osimertinib therapy (Figure 3).

In FANSS, the detection rate of invasive lung adenocarcinoma among non-smoking Asian women is comparable to that of the TALENT study but higher than that of the NLST study. Importantly, FANSS defines a positive screening as Lung-RADS 3 or 4, solid or part-solid nodules ≥6 mm, and ground-glass opacities (GGO) ≥30 mm. If aligned with the TALENT study’s criteria of GGO ≥5, it’s estimated that 1/4 to 1/3 of the population could have invasive lung adenocarcinoma (2-3 cases), potentially increasing the lung cancer detection rate to 2.5%-2.9% (Figure 4).

FANSS study data suggest that lung cancer screening is feasible for non-smoking Asian women, with preliminary results showing a detection rate of 1.5%, similar to the TALENT study. In the future, it’s worth exploring and considering expanding lung cancer screening guidelines to include non-smoking populations [6].

Factors Possibly Contributing to High Incidence of Lung Cancer in Non-Smoking Women

The mechanisms behind the high incidence of lung cancer in non-smoking Asian women are not yet fully understood. Several studies suggest that this phenomenon may be related to the following factors:

1. Genetic Variations:

A genome-wide association study identified new lung cancer susceptibility loci closely associated with non-smoking female lung cancer patients in Asia [7].

2. Family Heredity:

Research in China showed that non-smoking women with a family history of lung cancer had a 1.5-fold higher risk compared to those without such a history. The risk increased with the number of relatives affected by lung cancer [8].

3. Secondhand Smoke:

Many non-smoking lung cancer patients, particularly females, had exposure to secondhand smoke. Exposure to secondhand smoke, especially from spouses in the home and workplaces, increased the risk of lung cancer in non-smoking individuals [9].

4. Indoor Air Pollution:

A case-control study in China found that lung cancer in non-smoking women was closely related to various indoor air pollution sources, including exposure to environmental tobacco smoke at work, frequent cooking, using solid fuels for cooking, and heating [10].

Two Screening Recommendations for Low-Risk Individuals, Including Non-Smoking Women

Currently, there are no guidelines recommending routine lung cancer screening for low-risk individuals, including non-smoking women. This hesitation primarily stems from concerns about the radiation exposure from CT scans and the potential for overdiagnosis and overtreatment. However, the goal of screening low-risk individuals is not to perform more CT scans but rather to reduce the frequency of CT scans through careful and standardized follow-up processes to minimize radiation exposure. Additionally, overdiagnosis and overtreatment can be controlled reasonably, and avoiding necessary actions is not advisable [11].

For low-risk individuals, a review article by Professor Chen Haiquan and colleagues from Fudan University Affiliated Cancer Hospital, published in the “Chinese Journal of Cancer,” suggests two strategies [11]:

Strategy 1: Shift Baseline CT to Around Age 30

The age of 30 serves as the starting point for all lung cancer studies. Shifting the baseline CT to an earlier age is mainly aimed at detecting early-stage lung cancer as early as possible and laying a quantitative foundation for subsequent screening plans.

The primary difference between lung cancer in low-risk and high-risk individuals lies in the younger age and less aggressive biological behavior of tumor populations. Therefore, the timing of the first CT scan needs to be advanced to ensure broader coverage.

Strategy 2: Extend Follow-Up Intervals

After the first LDCT, it is recommended to adjust the follow-up intervals based on age and other risk factors (Figure 6). The goal is to minimize the number of follow-up CT scans and increase the chances of detecting cancer progression.

For individuals under 50, the interval can be extended to 5-10 years. However, for those aged 50-60 without other risk factors, the interval is 5 years, but if atleast one other risk factor is present, the interval is reduced to 3 years.

If nodules are discovered during the first LDCT scan, the patient should undergo further nodule assessment and diagnosis [11].

In conclusion, there is a need for increased attention to lung cancer in low-risk individuals, including non-smoking Asian women.

In clinical practice, a balanced, appropriate, non-conservative, and non-aggressive strategy should be considered, and LDCT screening should be conducted sensibly.

This approach will lead to early diagnosis and treatment for more patients and ultimately improve survival rates [11].

References:

[1] Sun S, Schiller JH, Gazdar AF. Lung cancer in never smokers-a different disease[J]. Nat Rev Cancer. 2007 Oct;7(10):778-90.

[2] China Lung Cancer Early Diagnosis and Treatment Expert Group, Western China Lung Cancer Research Collaborating Center. China Lung Cancer Low-dose CT Screening Guidelines (2023 Edition). Chinese Journal of Lung Cancer, 2023, 26(1): 1-9.

[3] https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/lung-cancer-screening.

[ 4] Yang P. 2021 WCLC. https://www.jto.org/article/S1556-0864(21)00360-9/fulltext.

[ 5] National Lung Screening Trial Research Team. Results of initial low-dose computed tomographic screening for lung cancer[J]. N Engl J Med. 2013 May 23;368(21):1980-91.

[6] Shum E, Li W, Bell J, et al. Preliminary Results from the Female Asian Nonsmoker Screening Study (FANSS). 2023 WCLC. OA16.04.

[7] Lan Q, Hsiung CA, Matsuo K, et al. Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia[J]. Nat Genet. 2012 Dec;44(12):1330- 5.

[ 8] Wang F, Tan F, Wu Z, et al. Lung cancer risk in non-smoking females with a familial history of cancer: a multi-center prospective cohort study in China[J]. J Natl Cancer Cent. 2021; 1(3): 108-114.

[9] Zhang Yachen, Liang Di, Jin Jing, et al. Research progress on risk factors for lung cancer in non-smokers [J]. Cancer Prevention and Treatment Research, 2017, 44(7): 501-505.

[10] Mu L, Liu l, Niu RG, et al. Indoor air pollution and risk of lung cancer among Chinese female non-smokers[J]. Cancer Causes Control. 2013 Mar;24(3):439-50.

[ 11] Zhou Yaodong, Chen Zongwei, Chen Haiquan. Lung cancer screening strategy for non-high-risk groups [J]. Chinese Journal of Cancer, 2020, 30(10): 726-732.

(source:internet, reference only)

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