“Although surgery for early-stage non-small-cell lung cancer (NSCLC) is known to have a substantial impact on health-related quality of life (HRQOL), there are few published studies about HRQOL in the longer term,” Dr. Patricia Kenny, of the University of Technology, Sydney, New South Wales, Australia, and colleagues write.

The researchers examined short- and long-term HRQOL and survival in the 2 years after surgery in patients with clinical stage I or II NSCLC (n = 173). The patients completed HRQOL questionnaires before surgery, at discharge, 1 month after surgery, and then every 4 months for 2 years.

Overall, 36% of patients experienced disease recurrence within 2 years. Of these, 55% received palliative radiotherapy and 24% received palliative chemotherapy. The mean time from surgery to disease recurrence was 10.7 months. Postoperative in-hospital mortality was 3%. The 2-year survival rate was 65.2%.

Of the 173 patients, 10 had no postoperative HRQOL data. The patients showed substantial deterioration across all HRQOL domains except emotional functioning after surgery. For the patients without disease recurrence, HRQOL improved in the 2 years after surgery. However, approximately half of these patients continued to experience symptoms and functional limitations. Patients who experienced disease recurrence within 2 years had some early postoperative improvement in HRQOL, with subsequent deterioration in most domains.

“These results can provide useful information for clinicians preparing patients for lung cancer surgery,” Dr. Kenny’s team writes. “Although few (if any) would decline surgery, informed decision making requires a full understanding of the potential outcomes (including HRQOL). Information about the continuing HRQOL effects can also contribute to ensuring that appropriate ongoing management and support are provided.”

CT screening of current and former smokers is used at a number of centers based on the belief that such screening will catch lung cancer at an early, more curable stage. However, there are limited data to support that screening actually improves outcomes.

In the present study, reported in the Journal of the American Medical Association for March 7, Dr. Peter B. Bach, from the Memorial Sloan-Kettering Cancer Center in New York, and colleagues assessed the outcomes of 3246 asymptomatic current or ex-smokers who were screened for lung cancer starting in 1998. The median follow-up period was 3.9 years.

Low-dose CT screening was performed on an annual basis with standard treatment applied to any detected lesions.

As noted, CT screening did increase detection of lung cancer. A total of 144 people were diagnosed with lung cancer when only 44.5 cases were expected. Similarly, 109 patients underwent lung resections, while just 10.9 cases were expected.

CT screening also did not result in detection in fewer cases of advanced lung cancer. In fact, the number diagnosed exceeded the number expected: 42 vs. 33.4. Similarly, deaths from lung cancer did not fall either: 38 occurred vs. 38.8 expected.

As Dr. Brach’s group mentions, “formulation of (a CT-based) screening policy should await the rigorous assessment that will be provided by ongoing randomized controlled trials (the National Lung Screening Trial and the NELSON Trial),” Drs. William C. Black and John A. Baron, from Dartmouth Medical School in Hanover, New Hampshire, note in a related editorial.

“Although expensive and time-consuming, rigorous trials of cancer screening are far more cost-effective than what might be the alternative – widespread adoption of costly screening interventions that cause more harm than good,” they add.

An association between textile jobs and a reduced lung cancer risk was first noted in the 1970s. The endotoxin was thought to mediate this effect by altering the innate and acquired immune systems. However, data examining the effect of endotoxin exposure on lung cancer risk have been lacking.

Dr. George Astrakianakis, from the Occupational Health and Safety Agency for Healthcare in Vancouver, British Columbia, and colleagues used various measures to quantify endotoxin exposure in 628 female textile workers in Shanghai who developed lung cancer and in 3184 controls who did not.

The researchers report their findings in the Journal of the National Cancer Institute for March 7th.

Cumulative endotoxin exposure showed a strong, significant inverse relationship with lung cancer risk, the report indicates. This was most apparent with a 20-year lag time: the highest quintile of exposure cut the risk by 40% compared with no exposure (p = 0.002).

The researchers estimate that endotoxin exposure in this cohort of workers reduced the occurrence of lung cancer by about 7.6 cases per 100,000.

“These findings indicate that endotoxin exposure is positively associated with early-stage anticarcinogenic activity in humans,” the researchers conclude. “Biologic plausibility for this association is supported by experimental research and corroborative evidence for reduced lung cancer among endotoxin-exposure in other industries.”

Dr. Jan P. van Meerbeeck, from University Hospital Ghent in Belgium, and his associates studied 332 patients with stage IIIA-N2 cancer who responded to three cycles of platinum-based chemotherapy. Patients were randomly assigned to radiotherapy (n = 165) or to surgery (n = 167).

Subjects were registered between 1994 and 2002 from 41 institutions in Europe; median follow-up was approximately 6 years. The results are published in the Journal of the National Cancer Institute for March 21.

Median survival was 17.5 months in the radiotherapy arm and 16.4 months in the surgery arm. Progression-free survival was 11.3 months and 9 months, respectively. The differences were not statistically significant.

Dr. van Meerbeeck’s group points out that surgery is of dubious value when mediastinal involvement persists after induction chemotherapy, and that the likelihood of survival is reduced if resection is incomplete.

They conclude that “in view of its low morbidity and mortality, radiotherapy is to be considered the preferred locoregional treatment” for patients with stage IIIA-N2 non-small-cell lung cancer.

In a related editorial, Dr. David H. Johnson, from Vanderbilt University School of Medicine in Nashville, Tennessee, and associates don’t totally agree, noting that some of these patients “may still be appropriately managed by resection rather than radiation.” They base this on the trial finding that local control was better in the surgical arm.

Moreover, they add, “careful interdisciplinary planning of patient care at the time of diagnosis to optimize selection of the local control modality is essential to achieving the best outcome in this patient population.”

Principal investigator Dr. Claudia I. Henschke said that when conducting such screening “it is important to follow a well-defined and well-tested algorithm — or approach — which defines who needs further workup and what and when that workup should be done.”

The study appears after a study in the March 7, 2007 issue of JAMA that found no meaningful reduction in deaths from lung cancer due to CT screening. A much larger study of 50,000 people, sponsored by the National Cancer Institute, is now underway that researchers say will be more definitive.

In the current study, Dr. Henschke, of New York Presbyterian Hospital-Weill Cornell Medical Center, and colleagues studied 6295 subjects with a median age of 66 years and a median smoking history of 40 pack-years.

Initial CT imaging led to recommendations for further workup in 906 (14.4%) of the baseline screenings and 361 (6.0%) of the 6014 annual repeat screenings.

In total, 101 patients had a diagnosis of lung cancer following the baseline screening. Another 3 participants had such a diagnosis following symptoms which appeared before the repeat screening. In all, 95 (91.3%) of these patients had no evidence of metastasis.

In the 20 patients in whom the diagnosis of lung cancer was made following the repeat screening, 17 (85%) had no evidence of metastasis.

Of a total of 134 recommended biopsies, 125 (93.3%) resulted in the diagnosis of lung cancer or another malignancy.

“These figures are very similar to those with mammography screening and quality assurance of mammography screening has proven highly successful in providing early diagnosis and early treatment for breast cancer,” Dr. Henschke said.

“We have shown that we can diagnosis lung cancer early, early treatment of early lung cancer is usually curative,” she concluded.

“Since many patients in our study had no other treatment options,” researcher Dr. Damian E. Dupuy said, “our results show the utility of lung radiofrequency ablation for this group of elderly sick people.”

Dr. Dupuy and colleagues at Brown Medical School/Rhode Island Hospital, Providence conducted a retrospective review of 153 patients (mean age, 68.5 years) with 189 primary or metastatic inoperable lung cancers. All underwent percutaneous fluoroscopic CT-guided radiofrequency ablation.

Survival rates for stage I non-small cell lung cancer ranged from 78% at 1 year to 27% at 5 years. Corresponding survival rates for colorectal pulmonary metastasis were 87% and 57%.

For tumors of 3 cm or smaller, local tumor progression-free survival rates were 83% at 1 year and 47% at 5 years. For larger tumors, these rates were significantly less, 45% and 25%.

The overall 30-day mortality rate was 3.9% (six patients). Four of these patients (2.6%) died of procedure-specific causes.

The researchers conclude that lung radiofrequency ablation appears to be safe and linked with promising long-term survival and local tumor progression outcomes, especially given the patient population treated.

“With improvements in lung cancer detection with CT screening looming on the horizon,” Dr. Dupuy added, “and improvements in image-guided ablation technology, I strongly believe that ablation may replace surgery in select populations with early stage lung cancer.”

“While waiting for a tailored, more rational approach to lung cancer treatment,” lead researcher Dr. Anna Ceribelli said, “we believe that empirical strategies using chemotherapeutic drugs are still a reasonable alternative for patients with advanced NSCLC.”

In this context, she added, “the sequential regimen evaluated in our paper, with cisplatin and gemcitabine followed by weekly docetaxel as first-line treatment appears to have a favorable cost-benefit ratio in terms of extremely manageable toxicity and activity.”

In the February 15th issue of Cancer, Dr. Ceribelli of the Regina Elena National Cancer Institute, Rome, and colleagues note that they adopted this approach in 52 patients with stage IIIb/IV disease.

Patients were given cisplatin on day 1 and gemcitabine on days 1 and 8 every 3 weeks for three cycles. Those without progression went on to receive docetaxel every week for 6 of 8 weeks for two cycles.

The overall response rate was 36.5%, the median overall survival was 11 months and the median progression-free survival was 6 months. Survival at 1 year was 48%, and at 2 years it was 25%. Corresponding progression-free survival rates were 12% and 9%.

“Both phases of the treatment were well tolerated,” the researchers report.

Given the tolerability, especially in regard to cumulative neurotoxicity, and the favorable response, concluded Dr. Ceribelli, the approach “could be considered for further evaluation.”

Incidental identification of lung tumors will be more common as imaging for coronary screening, pulmonary embolism, aortic disease, and abdominal pain increases, the investigators note.

As yet, however, screening is not recommended for lung cancer, which may be one reason why lung cancer survival is as low now as it was 30 years ago, whereas survival from other cancers has improved because of routine screening, Dr. Dan J. Raz and his associates note in the Journal of Thoracic Oncology for February.

Dr. Raz and his team identified 274 patients who underwent surgical resection of lung cancer with negative margins at their hospital between 1999 and 2004. Of these, 100 had incidentally detected tumors.

Initially, most indications for imaging were screening chest x-ray, preoperative chest x-ray, staging of another type of cancer, and evaluation of chest symptoms, such as pneumonia and MI. Other reasons included evaluation of non-chest pain, trauma, interstitial lung disease and coronary screening.

“Not surprisingly,” the investigators write, “patients with incidentally detected lung cancer had smaller cancers and earlier-stage disease.” In fact, half of all patients with stage I non-small cell lung cancer had incidentally detected lung cancers.

Of the 23 patients with bronchioloalveolar carcinoma, 65% were detected incidentally, compared with 34% of all other histologic subtypes (p = 0.003). It is not clear whether most of these would remain slow-growing and noninvasive if not treated, the authors note, or if they’re likely to evolve into adenocarcinomas.

As noted, incidental tumors were less likely to require pneumonectomy, which carries greater perioperative morbidity and mortality than lobectomy.

After adjusting for stage, the duration of survival was similar between incidental and symptomatic lung cancers. However, for the 17 lesions detected by computed tomography, the stage-adjusted hazard radio of death was 0.47 for incidental cancers, though the sample size was too small to establish statistical significance.

“Screening high-risk patients with chest CT may result in lung cancer overdiagnosis, especially in women,” Dr. Rebecca M. Lindell from the Mayo Clinic, Rochester, Minnesota said.

Dr. Lindell and associates evaluated the size, morphology, location, morphologic change, and growth rate of new and existing lung cancers detected in high-risk individuals who underwent annual screening chest CT for 5 years.

Sixty-one tumors were diagnosed in 1520 participants in the lung cancer screening study, the authors report. Thirty-one were incidence tumors and 30 were prevalence tumors.

The new cancers detected by CT were most commonly non-bronchoalveolar adenocarcinomas, the investigators say.

Mean volume doubling time in the 48 tumors that could be assessed was 518 days, the results indicate. The 13 tumors with a volume doubling time longer than 400 days were stage IA (10 tumors), IB (1 tumor), or II (2 tumors).

Eleven of the 13 overdiagnosed tumors (that is, those with a volume doubling time in excess of 400 days) occurred in women, the report indicates.

Tumors were more commonly detected in the right lung than in the left lung, the researchers note, and most tumors were in the upper lobes.

“Overdiagnosis, especially in women, may be a substantial concern in lung cancer screening,” the authors conclude.

“The effectiveness of lung cancer screening hasn’t been proven; therefore, one can not assess the cost-effectiveness yet,” Dr. Lindell added.

“With lung cancer persisting as the leading cause of cancer mortality in the US, research into the epidemiology of lung cancer in never smokers should be an important public health priority,” Dr. Heather A. Wakelee, from Stanford University School of Medicine in California, and colleagues emphasize in their report in the Journal of Clinical Oncology for February 10.

Smoking remains the main etiologic factor in lung cancer, the investigators note. As such, few studies have looked at the occurrence of this malignancy among nonsmokers.

Dr. Wakelee’s team assessed the epidemiology of lung cancer in never smokers by analyzing data from six large prospective cohorts: the Nurses’ Health Study, the Health Professionals Follow-up Study, the California Teachers Study, the Multiethnic Cohort Study, the Swedish Lung Cancer Register in the Uppsala/Orebro region, and the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study.

In never smokers between 40 and 79 years of age, the incidence rates of lung cancer in these cohorts were 14.4 to 20.8 per 100,000 person-years for women and 4.8 to 13.7 per 100,000 person-years and men.

The results also indicate that the lung cancers that affect never smokers are distinct from those typically seen in smokers. For example, cancers in never smokers respond differently to epidermal growth factor receptor inhibitors and are more likely to show adenocarcinoma histology.

The pathogenesis of lung cancer in never smokers is not completely understood, but second-hand smoke exposure probably plays a role.

“We know that secondhand smoke does increase the risk of lung cancer,” co-author Dr. Ellen Chang said in a statement. “So, it’s likely that a lot of these cases we observe are attributable to that.”