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concentration to limit toxicity is of principal ?importance. But, treatment with ICIs can ?occasionally be associated with durable remissions 9.?
Lung cancer had conventionally been well-thought-out as nonimmunogenic, and numerous ?efforts to modulate the immune system to treat lung cancer by nonspecific agents such as ?interleukin-2 (IL-2), interferon, and Bacillus Calmette–Guerin were ineffective. Efforts to ?unleash the immune system by means of several vaccines were also unsuccessful 10.?
Recent better therapeutic strategies like the commencement of the immune cascade is a ?multifaceted, multistep process 11-13. ?
Multiple agents inhibiting the PD-1/PD-L1 pathway have been approved for use as second-line ?agents in non-small cell lung cancer (NSCLC) and some of them got approved as frontline ?treatment in NSCLC patients, with some label restriction to some patients with high PD-L1 ?expression 14-16.?

Descriptive Epidemiology ?

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Races and Age risk
?
Age Lung cancer risk rises with age in both ?smokers and never smokers. The age-standardized ?death rate from lung cancer was roughly 40% higher ?among African American than white ?women who reported never smoking , ?but a statistically significant racial difference was not ?seen for never smoking women ?; there were insufficient data to measure the risk in black ?men 71. ?
Patients older than 80 years constitute 14% of all patients with lung cancer in the United ?States but account for almost a quarter of all lung cancer deaths 76, 77. ?

Genetic Factors ?
There is a genetic component to the pathogenesis of lung cancer, whether it relates to host ?susceptibility to lung cancer, with or without exposure to cigarette smoke to the ?development of certain types of lung cancer, or to an individual’s responsiveness to biologic ?therapies 73, 74.?
Smokers with history of early commencement of lung cancer in their first degree relatives ?have increased risk for lung cancer with growing older in age than smokers lacking such a ?family history 75.?
High incidence of HPV DNA in lung cancer has been reported in Asian cohorts, especially in ?nonsmokers; alternatively, studies in Western Europe failed to show an etiologic role of HPV ?in lung cancer 85-87.?

Correlation between NSCLC and smoking
Overwhelmingly, the major risk factor for lung cancer is cigarette smoking with a relative risk ?of 20 to 25 and an attributable risk of 85% to 90% 93.?
A little more than half of the lung cancers prompted by factors other than active ?smoking ?occur in never smokers 20, 21. lung cancers that happen in never smokers ?differs from ?those that are diagnosed in smokers in their molecular profile and responsiveness to the ??targeted therapies. Primary factors meticulously knotted to lung cancer in never smokers ?embrace exposure to ?known and suspected carcinogens including radon, second-hand ?tobacco smoke, and ?other indoor air pollutants 22. ?
In five researches, investigators explored indoor contact to smoke from wood, straw, ?and ?further solid fuel and lung cancer risk amongst never smoking women 22. ?
A European cohort showed similar association of solid fuel use for heating and cooking with ?lung cancer risk; OR of lung cancer in lifetime users of solid fuel was 1.80; switching to ?nonsolid fuels resulted in lowered risk. It has been suggested that the lung cancer that arise ?from wood smoke may behave differently from lung cancer due to tobacco smoke 52.?

Lung Cancer Occurrence in Never Smokers ?
Nonsmokers inhale a mixture of side stream smoke and exhaled mainstream smoke ?that is ?mostly denoted to as secondhand smoke 23. ?
Roughly 10 – 15% of all lung ?cancers arise in never smokers, making lung cancer in never ?smokers one of the ?principal causes of cancer-related mortality 24, 25 ?
The excessive and extended use of tobacco was an imperative influence in the initiation of ?lung cancer, putting in consideration that lung cancer in a nonsmoker was infrequent; and ?there could be a lag period of 10 years or more between cessation of smoking and the ?clinical onset of carcinoma 26. ?
Although more than 80% of lung cancers occur in persons with tobacco exposure, fewer than ??20% of smokers develop lung cancer 27.?
There is relative risk of 2.1 for lung cancer compared with nonsmokers, with men who ?smoked 5 or more cigars a day having the greatest risk 28. ?
The increased risk for lung cancer for the reason that pipe smoking is comparable to cigar ?smoking 29, 30. ?
Also, active pipe smoking was associated with a relative risk for lung cancer of 5.0.48 Cigar ?and pipe smokers have a larger risk for lung cancer than lifelong nonsmokers or ex-smokers ??31.?
The overall global statistics estimation is that 15% of lung cancers in men and up to 53% in ?women are not attributable to smoking, with never smokers accounting for 25% of all lung ?cancer cases globally 32.?
If lung cancer in never smokers were considered unconnectedly, it would rank as the seventh ?most common cause of cancer death globally before cervical, pancreatic, and prostate cancer ??33. ?
Regarding the demographics between smokers and nonsmokers, the best statistical analysis ?was done in North America since the fifties. ?
In the United States, one study valued that 19% of lung cancer in women and 9% of lung ?cancer in men arises in never smokers 34. ?
A series following 12,000 patients with lung cancer in California found a dramatic increase in ?broncho-alveolar carcinoma in never smokers from 19% during 1995 to 1999 to 26% during ??1999 to 2003 35.?

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