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The presence of subsolid nodules (SSNs) in the lung can be considered a biomarker of cancer risk, and should be managed with active surveillance rather than early resection, according to a European research group.

Analysis of 9.3 years of follow-up from the ongoing Multicenter Italian Lung Detection (MILD) trial showed that a lung cancer-specific mortality in patients with SSNs (sometimes called ground-glass opacities) was significantly increased with a hazard ratio of 3.80 compared to those without lung nodules.

However, the hazard ratio for lung cancer diagnosis in patients with SSNs was 6.77, with 73% of cancers not arising from SSNs, Mario Silva of the University of Parma, Italy, and colleagues reported online in the .

After a median active surveillance period of 77 months, most of the participants with SSNs who were diagnosed with lung cancer developed a cancer elsewhere in the lungs, the researchers said. The lung cancer specific survival in participants with SSN-derived lung cancer was 100% compared to 63.6% for lung cancers not derived from SSNs, extrapulmonary cancer, and non-neoplastic disease.

The findings also indicated that techniques other than visual detection by a radiologist may prove helpful in finding smaller nodules and perhaps lung cancers at an earlier stage, the study authors said.

"These results demonstrate the safety of active surveillance for conservative management of [SSNs] until signs of solid component growth," they wrote.

In patients with multiple comorbidities and more aggressive lung cancers, this conservative approach to management of SNNs will reduce unnecessary surgery and risk of cardiopulmonary damage, Silva and colleagues said. "We suggest that subjects with SSNs might be a suitable target population for pharmacological smoking-cessation and chemoprevention trials."

The researchers emphasized that prolonged follow-up is crucial due to the high risk of cancer elsewhere in the lung as well as extrapulmonary cancer. The median time to diagnosis after SSN discovery was 52 months, the study showed.

The protocol has used long-term surveillance to monitor SSNs since 2005, the study authors said. "Such a conservative strategy for slow-growing tumors enabled us to evaluate the progression rate of [SSNs] and their long-term outcome, as reported in a previous paper analyzing the first 5-year followup."

When asked to comment, Hossein Borghaei, DO, MS, chief of thoracic medical oncology at Fox Chase Cancer Center in Philadelphia, said that at this point, the lack of prospective data from large randomized studies means that "management of these nodules is decided on a case-by-case basis and by the individual treating physicians."

Borghaei agreed with the study authors that clinicians "will be seeing more and more of these cases as lung cancer screening becomes more commonplace." However, he told 番茄社区app, "additional data is needed for us to establish clear guidelines for the management of these abnormalities seen on CT images."

In patients with a history of lung cancer as well as in those without, "we often debate if an intervention is needed at the time of detection of a nodule," said Borghaei. "Clearly, in a patient with a history of lung cancer there is more concern about a recurrence or emergence of another lung cancer."

At Fox Chase, these cases are discussed at multi-disciplinary tumor board conferences, he said. Once consensus is reached, the treatment plan is presented to the patient. "This approach is preferred because the radiologists, pulmonologists, surgeons, radiation and medical oncologists are all looking at the same data and discussing the same patient simultaneously," he explained.

For the current study, 2,303 patients were randomized to the volumetric thin-slice low-dose computed tomography (LDCT) arm of the ongoing MILD study. SSNs were detected in 16.9% (389). The median age of the participants was 58.1 years and the median cumulative tobacco exposure was 43.6 pack years.

When compared to patients with solid nodules, those with SSNs were significantly more likely to be female (40.4% versus 29.5%), active smokers (73.8% versus 66.8%), and eligible by National Lung Screening Trial selection (58.9% versus 52.8%) defined as an age ≥55 years and a smoking history of ≥30 pack-years.

All SSNs were classified into non-solid nodules (NSNs) or part-solid nodules (PSN). The volume of SSNs, measured using semi-automatic , included the whole non-solid component (NSN and PSN) and the solid component (PSN).

NSNs and PSNs with a solid component <5 mm were managed conservatively with annual LDCT, regardless of the size of the non-solid component. Management of a PSN with a new or growing solid component with a diameter ≥5 mm was determined by a multidisciplinary team.

The volume of SSNs and the frequency of lung cancer in other sites of the lung showed a non-statistically significant higher frequency in participants with SSN volume above median (7.2%) compared with those below (4.1%).

"The relatively small number of this population might have limited the statistical power of such association," the researchers pointed out. More investigation in larger populations should address this, they added.

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