Stage IA Non-small Cell Lung Cancer Research Articles

Long Interspersed Nuclear Element 1 Hypomethylation Is a Marker of Poor Prognosis in Stage IA Non–Small Cell Lung Cancer

Global hypomethylation and the hypermethylation of gene promoter regions are common events in tumor DNA. The aim of this study was to evaluate the prognostic significance of both global hypomethylation and gene promoter hypermethylation in DNA from non-small cell lung cancer (NSCLC). Genomic DNA was obtained from the tumor tissue of 379 NSCLC patients who underwent surgery. Methylation levels were measured by real-time PCR following bisulfite modification of DNA and were correlated with clinicopathologic parameters and patient prognosis. Methylation of long interspersed nuclear element 1 (LINE-1) was used as a surrogate marker for global methylation. Hypermethylation of the APC, CDH13, and RASSF1 promoter regions was also evaluated. Tumor tissue showed significantly higher CDH13 and RASSF1 methylation levels compared with normal lung tissue, but lower LINE-1 methylation levels. APC, RASSF1, and LINE-1 methylation levels were significant prognostic factors in univariate analysis of an initial cohort of 234 cases. APC and LINE-1 methylation remained significant prognostic factors in multivariate analysis that included age, gender, smoking history, histologic type, and pathologic stage. LINE-1 methylation showed marginally significant prognostic value in stage IA and IB disease. Expansion of the study cohort to 364 cases revealed that LINE-1 methylation had significant prognostic value for stage IA NSCLC patients in multivariate analysis. LINE-1 hypomethylation was an independent marker of poor prognosis in stage IA NSCLC. Validation of this finding in additional tumor cohorts could have clinical relevance for the management of early-stage NSCLC.

Prognostic Significance of Intratumoral Blood Vessel Invasion in Pathologic Stage IA Non-Small Cell Lung Cancer

The 5-year survival rate of pathologic stage IA non-small cell lung cancer (NSCLC) is excellent; however, up to 10% of patients with pathologic stage IA NSCLC still relapse postoperatively and die. This study retrospectively analyzed the clinicopathologic features of patients with pathologic stage IA NSCLC to identify the prognostic factors and investigate the effect of a combination of intratumoral vessel invasion and tumor size. From December 1991 to December 2003, 217 consecutive patients with stage IA NSCLC were selected, and disease-free survival (DFS) was analyzed. Intratumoral blood vessel invasion (BVI) was identified as an independent poor prognostic factor (p = 0.0006). The relative risk for patients with BVI was 4.599 times higher than that for patients without BVI (95% confidence interval, 1.913 to 11.056). According to the new T N M system, the difference in DFS between the patients with and without BVI was statistically significant, not only in tumors exceeding 2 cm (T1b with BVI vs T1b without BVI, p = 0.0020) but also in tumors smaller than 2 cm (T1a with BVI vs T1a without BVI, p < 0.0001). The survival curve of T1b patients without BVI was similar to that of T1a patients without BVI (p = 0.0892). Distant recurrence was frequently observed in both T1a and T1b patients with BVI. BVI is an independent poor prognostic factor in patients with pathologic stage IA NSCLC. These T1a and T1b patients with BVI both might benefit from adjuvant chemotherapy.

CyberKnife radiosurgery for inoperable stage IA non-small cell lung cancer: 18F-fluorodeoxyglucose positron emission tomography/computed tomography serial tumor response assessment

ObjectiveTo report serial 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) tumor response following CyberKnife radiosurgery for stage IA non-small cell lung cancer (NSCLC).MethodsPatients with biopsy-proven inoperable stage IA NSCLC were enrolled into this IRB-approved study. Targeting was based on 3-5 gold fiducial markers implanted in or near tumors. Gross tumor volumes (GTVs) were contoured using lung windows; margins were expanded by 5 mm to establish the planning treatment volumes (PTVs). Doses ranged from 42-60 Gy in 3 equal fractions. 18F-FDG PET/CT was performed prior to and at 3-6-month, 9-15 months and 18-24 months following treatment. The tumor maximum standardized uptake value (SUVmax) was recorded for each time point.ResultsTwenty patients with an average maximum tumor diameter of 2.2 cm were treated over a 3-year period. A mean dose of 51 Gy was delivered to the PTV in 3 to 11 days (mean, 7 days). The 30-Gy isodose contour extended an average of 2 cm from the GTV. At a median follow-up of 43 months, the 2-year Kaplan-Meier overall survival estimate was 90% and the local control estimate was 95%. Mean tumor SUVmax before treatment was 6.2 (range, 2.0 to 10.7). During early follow-up the mean tumor SUVmax remained at 2.3 (range, 1.0 to 5.7), despite transient elevations in individual tumor SUVmax levels attributed to peritumoral radiation-induced pneumonitis visible on CT imaging. At 18-24 months the mean tumor SUVmax for controlled tumors was 2.0, witha narrow range of values (range, 1.5 to 2.8). A single local failure was confirmed at 24 months in a patient with an elevated tumor SUVmax of 8.4.ConclusionLocal control and survival following CyberKnife radiosurgery for stage IA NSCLC is exceptional. Early transient increases in tumor SUVmax are likely related to radiation-induced pneumonitis. Tumor SUVmaxvalues return to background levels at 18-24 months, enhancing 18F-FDG PET/CT detection of local failure. The value of 18F-FDG PET/CT imaging for surveillance following lung SBRT deserves further study.

Robotic Brachytherapy and Sublobar Resection for T1 Non-Small Cell Lung Cancer in High-Risk Patients

Sublobar lung resection and brachytherapy seed placement is gaining acceptance for T1 non-small cell lung cancer (NSCLC) in select patients with comorbidities precluding lobectomy. Our institution first reported utilization of the da Vinci system for robotic brachytherapy developed experimentally in swine and applied to high-risk patients 5 years ago. We now report seed dosimetrics and midterm follow-up. Eleven high-risk patients with stage IA NSCLC who were not candidates for conventional lobectomy underwent limited resection of 12 primary tumors. To reduce locoregional recurrence, (125)I brachytherapy seeds were robotically sutured intracorporeally over resection margins to deliver 14,400 cGy 1 cm from the implant plane. Patients were followed with dosimetric computed tomography scans at 30 +/- 16 days. Survival and sites of recurrence were documented. Resected tumor size averaged 1.48 +/- 0.38 cm (range, 1.1 to 2.1 cm). Perioperative mortality was 0% and recurrence was 9% (1 of 11 [margin recurrence at 6 months with resultant mortality at 1 year]). Follow-up duration was 31.82 +/- 17.35 months. Dosimetrics confirmed 14,400 cGy delivery using 24.21 +/- 4.6 (125)I seeds (range, 17 to 30 seeds) over a planning target volume of 10.29 +/- 2.39 cc(3). Overall, 84.1% of the planning target volume was covered by 100% of the prescription dose (V100), and 88.2% was covered by 87% of the prescription dose (V87), comparable to open dosimetric data at our institution. Follow-up imaging confirmed seed stability in all patients. Robotic (125)I brachytherapy seed placement is a feasible adjuvant procedure to reduce the incidence of recurrence after sublobar resection in medically compromised patients. Tailored robotic seed placement delivers an exact dosing regimen in a minimally invasive fashion with equivalent precision to open surgery.

Promoter hypermethylation of the p16 and Wif-1 genes as an independent prognostic marker in stage IA non-small cell lung cancers

Hypermethylation of promoter CpG islands is a major inactivation mechanism of tumor suppressor genes, some of which are thought to be related to the prognosis of patients with non-small cell lung cancer (NSCLC). Therefore, hypermethylation of the specific genes may be expected to serve as a prognostic biomarker for NSCLC. In this study, the methylation status of 14 genes was analyzed in 44 stage IA NSCLC cases using methylation-specific PCR. Hypermethylation was detected in PTGER2 (70% of cases), DRM/Gremlin (66%), sFRP-2 (57%), IL-12Rbeta2 (48%), Reprimo (41%), APC (39%), CXCL12 (39%), HPP1 (30%), SPARC (30%), sFRP-5 (30%), p16 (25%), RUNX3 (20%), sFRP-1 (20%) and Wif-1 (16%). Patients with p16, sFRP-5, Wif-1 or CXCL12 methylation had a significantly shorter duration of relapse-free survival than their counterparts with an unmethylated gene (p16, P=0.011; sFRP-5, P=0.030, Wif-1, P=0.036; CXCL12, P=0.026). Also, those with methylated HPP1, p16 or Wif-1 had a significantly shorter duration of overall survival (HPP1, P=0.031; p16, P=0.026; Wif-1, P=0.008). Multivariate analysis revealed that p16 methylation in relapse-free survival and Wif-1 methylation in overall survival were the strongest independent prognostic factors (p16, P=0.036; Wif-1, P=0.035). In conclusion, the hypermethylation of the p16 and Wif-1 genes has potential as biomarkers that may be used to predict the prognosis of stage IA NSCLC.

Subdivision of the T1 Size Descriptor for Stage I Non-small Cell Lung Cancer Has Prognostic Value: A Single Institution Experience

Non-small cell lung cancer (NSCLC) staging is currently being revised by the International Association for the Study of Lung Cancer (IASLC). Among other changes, the revised staging system proposes the subdivision of the T1 tumor (<or= 3 cm) category into the following two subgroups: T1a (<or= 2 cm); and T1b (> 2 cm but <or= 3 cm). This study investigated the prognostic differences between patients in these two T1 tumor subgroups. A total of 291 patients with stage IA (T1N0M0) NSCLC who had undergone surgical resection between January 1, 1991, and December 31, 2004, were identified by the cancer registry. The mean and median follow-up times were 62 and 54 months, respectively. The patients were subdivided into T1a and T1b groups. Overall survival (OS) as well as disease-free survival (DFS) periods were determined by retrospective chart review and compared for statistical significance. Patient-specific and disease-specific information was recorded in order to identify possible confounding variables. When patients were subdivided into T1a (n = 193) and T1b (n = 98) groups, significant differences were observed in both OS (p = .023) and DFS (p = .014). No statistically significant difference was detected in the mean age, pack-year smoking history, or percent predicted FVC or FEV(1) between the T1a and T1b groups. In addition, there was no statistically significant difference in the type of surgery or nodal staging performed on the patients in the two groups. The T1 descriptor should be subdivided at 2 cm to reflect the observed prognostic differences. Our findings agree with the new staging system proposed by the IASLC, revealing its profound applicability to individual institutions.

Long-term Surgical Outcome in Patients with Lung Cancer and Coexisting Severe COPD

The functional criteria for curative surgery for patients with non-small cell lung cancer (NSCLC) and coexisting chronic obstructive pulmonary disease (COPD) remain controversial. We aimed to clarify long-term outcomes after resection. Between January 1990 and April 2005, 36 consecutive patients with NSCLC and severe COPD underwent pulmonary resection. All had severe (30-50 % pred FEV1) or very severe COPD (30 % > pred FEV1) preoperatively. Survival, short- and long-term complications were analyzed retrospectively. Prognostic factors were also analyzed. The 5-year survival rate of these patients was significantly worse than that of patients with better pulmonary function (50 % < pred FEV1) ( P < 0.0001). Patients with interstitial pneumonia (IP) had a significantly poorer prognosis ( P = 0.0099). With regard to long-term complications three months after surgery, 30 % of patients reported worsening of dyspnea, and 20 % experienced pneumonia recurrence. No deaths were related to COPD progression. Patients with stage IA NSCLC and severe COPD may undergo curative surgical resection; however, postoperative complications and long-term survival remain unsolved problems. IP is a contraindication for surgery in patients with severe COPD.

Spontaneous pneumothorax after stereotactic radiotherapy for non-small-cell lung cancer

The report presented here describes a case of spontaneous pneumothorax observed after stereotactic radiotherapy (SRT) for non-small-cell lung cancer (NSCLC). An 84-year-old man with a Stage IIB, T3N0M0 NSCLC in the right upper lobe and a Stage IA NSCLC in the right lower lobe of the lung was treated with SRT for both tumors. He received SRT with a total dose of 60.0 Gy in 10 fractions delivered to the right upper lobe, and 48.0 Gy in 4 fractions delivered to the right lower lobe. Two months after completion of the treatment, he developed spontaneous pneumothorax. He was asymptomatic and recovered with conservative management. Spontaneous pneumothorax has occasionally been reported to occur following thoracic radiotherapy for malignancy. Almost all of the reported cases are patients who had received mantle irradiation for Hodgkin's disease. We have been unable to fi nd any reports of spontaneous pneumothorax after SRT, which has recently been used for treating patients with early-stage NSCLC. Because a case of spontaneous pneumothorax after SRT was observed in our institution, its clinical course is described here along with a discussion of possible causes of spontaneous pneumothorax.

Surgical treatment for non-small cell lung cancer in octogenarians - the usefulness of video-assisted thoracic surgery

The purpose of this study was to investigate whether surgical treatment for non-small cell lung cancer (NSCLC) confers a survival benefit in octogenarians, and whether video-assisted thoracic surgery (VATS) is effective in terms of postoperative morbidity, mortality, and quality of life (QOL). Among 1684 patients with primary NSCLC who underwent pathologically complete resection, 95 were octogenarians. Operation was performed by the VATS approach (VATS group, n=58) or the standard thoracotomy (ST group, n=37). Although postoperative cardiopulmonary complications occurred in 20 cases (21.1%), all were manageable. In the ST group cardiopulmonary complications occurred more frequently than in the VATS group (P=0.030). The overall 5-year survival rate of the 95 octogenarians, including deaths from all causes, was 54.4%. The overall 5-year survival rate of patients with stage IA disease was 65.2%. These outcome data were not significantly worse than those for patients aged 79 years or under (P=0.136). There was no significant difference in overall 5-year survival rates between the ST group and the VATS group (P=0.144). The VATS approach for pulmonary resection is recommended for octogenarians with NSCLC. Surgical resection is the optimal treatment for stage IA NSCLC, and therefore, advanced age is not a contraindication for curative resection.

The maximum standardized 18F-fluorodeoxyglucose uptake on positron emission tomography predicts lymph node metastasis and invasiveness in clinical stage IA non-small cell lung cancer

In patients with clinical stage IA non-small cell lung cancer (NSCLC), we investigated whether the maximum standardized uptake value (SUVmax) of 18F-fluorodeoxyglucose (FDG) by the tumor correlated with lymph node metastasis, intratumoral lymphatic and vascular invasion of tumor cells, and pleural invasion. From April 2005 to November 2008, 58 patients underwent a lobectomy with systematic hilar and mediastinal lymph node dissection for clinical stage IA NSCLC. All patients had integrated FDG-positron emission tomography (PET)/computed tomography (CT) performed in our center as part of the preoperative workup within one month of resection. The relationships between the SUVmax and pathologic results of lymph node metastasis, intratumoral lymphatic and vascular invasion of tumor cells, and pleural invasion were examined. Compared with tumors with an SUVmax < or = 2.0, tumors with an SUVmax>2.0 had more frequent lymph node metastasis, intratumoral lymphatic and vascular invasion of tumor cells and pleural invasion (all P<0.05). Our results suggest that in patients with clinical stage IA NSCLC, SUVmax is an important predictor of tumor invasiveness.

Feasibility of video-assisted thoracoscopic surgery segmentectomy for selected peripheral lung carcinomas☆

Segmentectomy for non-small cell lung cancer (NSCLC) is believed to increase the rates of recurrence and postoperative air leak. We sought to present our clinical data and outcome of VATS (video-assisted thoracoscopic surgery) segmentectomies with systematic node dissection for selected NSCLC patients. Inclusion criteria were clinical T1N0M0 peripheral NSCLC measuring <or=2 cm (n=38) and NSCLC with interlobar invasion, which cause positive surgical margin with malignancy after lobectomy of a primary lesion and only partial resection of invasion site (n=3). Outcome variables include hospital course, complications, mortality, recurrence patterns and survival. The intersegmental border was identified using the intersegmental veins as landmark and the demarcation between the resected (inflated) and preserved (collapsed) lungs. The intersegmental plane was divided by an endoscopic stapler and electrocautery. The mean operative time and intraoperative bleeding were 220 min (range 100-306) and 183 ml (30-730), respectively. The number of stapler cartridges used for intersegmental division was 2 (1-5). Postoperative air leak (>7 days), which required no surgical intervention, occurred in two patients. The chest tube drainage duration was 3 days. There were no in-hospital deaths. The numbers of resected subsegments and reserved subsegments in comparison with lobectomy were 5 (2-13) and 5 (3-13), respectively. The FEV1.0 after VS was higher than the predictive FEV1.0 after lobectomy, if the latter was performed as standard procedure. We experienced four cases of distant metastasis after segmentectomy, but there was no case of local recurrence. The 5-year survival and recurrence-free survival rates in pathological stage IA NSCLC were 89.9% and 93.3%, respectively. VATS segmentectomy with systematic node dissection is a reasonable treatment option for selected peripheral NSCLC.

Prognostic Significance of the Number of Lymph Nodes Removed at Lobectomy in Stage IA Non-small Cell Lung Cancer

Lobectomy with mediastinal lymph node dissection is the standard of care in stage IA non-small cell lung cancer (NSCLC). We investigated whether the number of lymph nodes removed influences survival in stage IA NSCLC patients who underwent lobectomy. 2545 stage IA NSCLC patients in the California Cancer Registry who underwent lobectomy between 1999 and 2003 were analyzed. Cox proportional hazards regression was used to identify independent prognostic factors. Increasing number of lymph nodes removed was associated with statistical significant improvements in overall survival (OS) (p = 0.0001) and lung cancer-specific survival (LCSS) (p = 0.0309) of stage IA NSCLC patients who underwent lobectomy. The number of lymph nodes removed remained an independent favorable prognostic factor for OS (ptrend = 0.0001) and LCSS (ptrend = 0.0095) even after adjustment for other independent prognostic factors including age, sex, histology, histologic grade, socioeconomic status, and marital status in the Cox proportional regression analyses. Removal of 11 to 15 lymph nodes conferred the lowest hazard ratio for death [versus none; hazard ratio = 0.52; 95% confidence interval: 0.36-0.75]. The number of lymph nodes removed in stage IA NSCLC patients who underwent lobectomy is an independent prognostic factor for OS and LCSS.

Impact of number of lymph nodes (LN) examined at the time of surgical resection (Sx) on the survival of stage IA non-small cell lung cancer (NSCLC) patients (pts)

7534 Background: Despite complete Sx pts with stage IA have an approx. 5yr survival of only 61%. Better prognostic factors need to be identified in this stage. In this study we evaluated the effect of detailed surgical LN exam on Progression Free Survival (PFS) and Overall Survival (OS) of these pts. Methods: All pts with pT1pN0M0 (stage IA) NSCLC from 11/2000 to 12/2006 at OSF Saint Francis Medical Center, Peoria, IL were deemed eligible. Log rank and Cox proportional hazard model (CPHM) was used to estimate survival rates and relative risks. For the purpose of analyses, number of LN examined was broken down in 4 groups; 1–3 (group1or G1), 4–6 (G2), 7–9 (G3), > 9 lymph nodes (G4). Results: Of the 112 eligible pts, analyses were performed on 98 pts with complete data on pathologic tumor stage, number of LN, grade, differentiation and race. Demographics are as follows: median age: 71 (33–83 yrs), median follow-up time: 2.08 years (0.07–5.31 yrs). LN groups pts numbers: G1: 33 (33.7%) pts, G2; 33 (33.7%) pts, G3: 19 (19.3%) and G4: 13 (13.3%). We observed a statistically significant increasing trend in PFS with increase in number of LN examined (Log Rank p-value=0.039). No significant trend in OS was observed with increase in number of LN (log-rank p-value=0.2). 4 yr PFS for G1, G2, G3, G4 was18.1%, 67.9%, 52.6%, 72.7%. 4 yr OS for G1, G2, G3, G4 was 38.3%, 73.8%, 52.6%, 87.5%. CPHM demonstrated an increase in survival of G2, G3 and G4 as compared to G1 (PF Hazard ratios: 0.37, 0.53, 0.26; Overall Hazard Ratios: 0.44, 0.74 and 0.33 respectively). Conclusions: This data suggests that there is a significant increase in PFS survival with increase in number of LN examined at surgery in stage IA NSCLC pts. No significant financial relationships to disclose.

Does Positron Emission Tomography Prevent Nontherapeutic Pulmonary Resections for Clinical Stage IA Lung Cancer?

The American College of Surgeons Oncology Group (ACOSOG) Z0050 trial demonstrated that positron emission tomography (PET) prevents nontherapeutic thoracotomies in a substantial fraction of patients with known or suspected non-small cell lung cancer (NSCLC). However, the benefit of PET in clinical stage IA patients has been questioned due to the lower prevalence of metastases and poor ability to discriminate benign from malignant lung lesions. This study evaluates whether PET prevents nontherapeutic pulmonary resections in clinical stage IA patients by finding advanced disease or by declaring a nodule as benign. We reanalyzed all patients with clinical stage IA NSCLC from ACOSOG Z0050. The clinical, PET, and pathologic stages were compared for this prospective cohort. One hundred twenty-two clinical stage IA patients were evaluated and 78.7% (96 of 122; 95% confidence interval [CI], 70.4 to 85.6) were eventually shown to have cancer. PET correctly showed 7.4% (9 of 122; 95% CI, 3.4 to 13.5) of patients to have advanced disease (stages IIIA to IV). However, due to a high false positive rate, the positive predictive value for advanced disease was only 33.3% (9 of 27; 95% CI, 16.5 to 54.0). The negative predictive value of PET to predict benign lesions was only 57% (16 of 28; 95% CI, 37.2 to 75.5). Thus, 43% (12 of 28; 95% CI, 24.5 to 62.8) of patients with a PET negative primary lesion actually had cancer, and all of these had resectable disease (stages IA to IIB). In clinical stage IA lung cancer patients, PET prevents nontherapeutic pulmonary resections less than 10% of the time. If a strategy of no surgery and serial computed tomographic scans is chosen for PET negative lesions, over 40% of patients with NSCLC will have surgery delayed. A prospective trial comparing PET versus resection for clinical stage IA lesions would clarify the value of PET for these patients.

Prognostic Significance of the Non–Size-Based AJCC T2 Descriptors: Visceral Pleura Invasion, Hilar Atelectasis, or Obstructive Pneumonitis in Stage IB Non-small Cell Lung Cancer Is Dependent on Tumor Size

<h3>Background</h3> The T2 descriptor for staging non-small cell lung cancer (NSCLC) contains several non–size-based criteria. It remains unknown whether the prognostic significance of these non–size-based criteria is dependent on tumor size. <h3>Methods</h3> A total of 10,545 patients with stage IB NSCLC from the California Cancer Registry between 1989 to 2003 were categorized into the following three nonoverlapping criteria: (1) tumor size (T2S); (2) visceral pleura invasion, hilar atelectasis, or obstructive pneumonitis (T2P); and (3) main bronchus involvement ≥ 2 cm from the carina (T2C). Univariate survival analyses were performed using the Kaplan-Meier method. Multivariate survival analyses were performed using Cox proportional hazards ratios. <h3>Results</h3> A total of 51.1% of patients with stage IB NSCLC were staged by T2S, 43.2% by T2P, and 5.7% by T2C; 2,224 stage IB patients (total, 21.1%; 18.9% T2P + 2.2% T2C) had tumors ≤ 3 cm in size. The 5-year survival rate and the median survival time of these stage IB patients with tumors ≤ 3 cm in size were as follows: T2P, 51.2% and 64 months, respectively; T2C, 49.0% and 58 months, respectively. These values were similar to the 53.2% 5-year survival rate and 67-month median survival time for patients with stage IA NSCLC (p = 0.40). Cox proportional hazards model revealed T2P of > 3 cm was a poor prognostic factor for survival (vs T2S; hazard ratio [HR], 1.16; 95% confidence interval [CI], 1.08 to 1.24). Conversely, T2P ≤ 3 cm was a favorable prognostic factor for survival (vs T2S; HR, 0.89; 95% CI, 0.82 to 0.96). T2C was not an independent prognostic factor for survival. <h3>Conclusions</h3> Prognostic significance of the non–size-based T2 descriptor T2P is dependent on tumor size.

Sublobar resections in stage IA non-small cell lung cancer: segmentectomies result in significantly better cancer-related survival than wedge resections☆

Sublobar resections spare pulmonary function and offer a method of increasing resection rates in patients with lung cancer and limited functional operability. Previous studies demonstrated an increased local recurrence rate following wedge resections compared to segmentectomies in stage IA non-small cell lung cancer (NSCLC). However, a prognostic impact of this observation has never been shown and is still under debate. Therefore, this study has been performed to analyse the cancer-related survival of sublobar resections in stage IA patients. Over a 17-year period 87 patients underwent sublobar complete resection (R0) of stage IA NSCLC via thoracotomy. Sublobar resection was reserved for patients with cardiopulmonary impairment. Wedge resections with selective lymphadenectomy were performed in 31 patients (36%) and segmentectomies with systematic lymphadenectomy in 56 patients (64%). Patient characteristics, functional parameters, tumour specifics and follow-up duration were analysed concerning their distribution between the two groups. Kaplan-Meier curves were compared and possible joint effects between prognostic parameters were analysed by multivariate Cox regression analysis. The median follow-up duration was 45 months. There was no significant difference between the two groups in gender (p=0.11), age (p=0.08), American Society of Anesthesiology physical performance status (ASA)-score (p=0.32), forced expiratory volume in 1s FEV(1) (p=0.08), tumour size (p=0.30), histology (p=0.17), grading (p=0.12), complication rate (p=0.15) and follow-up duration (p=0.29). The mean number of dissected lymph nodes in segmentectomies (12+/-6) was higher than in wedge resections (6+/-3) (p=0.0001). The 5-year survival rate was 63%. There were significantly less locoregional recurrences (p=0.001), an equal distribution of distant metastases (p=0.53) and a better cancer-related survival (p=0.016) following segmentectomies compared to wedge resections. Cox regression analysis showed that the prognostic effect of the resection type was independent from gender, age, ASA-score, respiratory function, tumour size, tumour histology, grading and number of dissected lymph nodes (p=0.04, relative risk 1.16). Studies investigating survival after sublobar resection of stage IA NSCLC should always distinguish between anatomical segmentectomies and wedge resections. If limited functional operability requires a sublobar resection of stage IA NSCLC, segmentectomy with systematic lymphadenectomy should be preferred.

Molecular Biologic Staging of Lung Cancer

Clinical and pathologic staging of lung cancer is suboptimal in achieving the goals of assessing prognosis and selecting therapy. Although the technologic developments that allow the generalized use of proteomic and genomic analyses are relatively recent, major progress in understanding the molecular basis of lung cancer has been made. Predicting survival is only the first step in the use of genomics and proteomics. If a reliable gene array or protein profile can be identified that is associated with poor prognosis, these profiles can then be identified and become potential therapeutic targets. It is not difficult to envision the development of a simple serum test that will diagnose a lung cancer perhaps even before it is clinically apparent and at the same time identify the chemotherapeutic agents to which the tumor is sensitive, allowing individually directed treatment. Eventually, a comprehensive staging system should incorporate the prognostic information of biologic variables.

Cancer Care Ontario and American Society of Clinical Oncology Adjuvant Chemotherapy and Adjuvant Radiation Therapy for Stages I-IIIA Resectable Non–Small-Cell Lung Cancer Guideline

To determine the role of adjuvant chemotherapy and radiation therapy in patients with completely resected stage IA-IIIA non-small-cell lung cancer (NSCLC). The Cancer Care Ontario Program in Evidence-Based Care and the American Society of Clinical Oncology convened a Joint Expert Panel in August 2006 to review the evidence and draft recommendations for these therapies. Available data support the use of adjuvant cisplatin-based chemotherapy in completely resected NSCLC; however, the strength of the data and consequent recommendations vary by disease stage. Adjuvant radiation therapy appears detrimental to survival in stages IB and II, with a possible modest benefit in stage IIIA. Adjuvant cisplatin-based chemotherapy is recommended for routine use in patients with stages IIA, IIB, and IIIA disease. Although there has been a statistically significant overall survival benefit seen in several randomized clinical trials (RCTs) enrolling a range of people with completely resected NSCLC, results of subset analyses for patient populations with stage IB disease were not significant, and adjuvant chemotherapy in stage IB disease is not currently recommended for routine use. To date, very few patients with stage IA NSCLC have been enrolled onto RCTs of adjuvant therapy; adjuvant chemotherapy is not recommended in these cases. Evidence from RCTs demonstrates a survival detriment for adjuvant radiotherapy with limited evidence for a reduction in local recurrence. Adjuvant radiation therapy appears detrimental to survival in stage IB and II, and may possibly confer a modest benefit in stage IIIA.

Carbon Ion Radiotherapy for Stage I Non-small Cell Lung Cancer Using a Regimen of Four Fractions during 1 Week

A phase I/II study was first conducted for the treatment of stage I non-small cell lung cancer (NSCLC) from 1994 to 1999 to determine the optimal dose. On the basis on the results, a phase II study using a regimen of four fractions during 1 week was performed. The purpose of the present study was to determine the local control and 5-year survival rates. From December 2000 to November 2003, 79 patients with 80 primary lesions were treated. Using a fixed dose of 52.8 GyE for stage IA NSCLC and 60.0 GyE for stage IB NSCLC in four fractions during 1 week, the primary tumors were irradiated with carbon beams alone. The average age of the patients was 74.8 years. Sixty-two (78.5%) of these patients were medically inoperable. Local control and survival were determined using the Kaplan-Meier method. The data were statistically processed using the log-rank test. All patients were observed for a minimum of 3 years or until death, with a median follow-up time of 38.6 months, ranging from 2.5 to 72.2 months. The local control rate for all patients was 90% (T1: 98%, T2: 80%). The patients' 5-year lung cancer-specific survival rate was 68% (IA: 87%, IB: 42%). The overall survival was 45% (IA: 62%, IB: 25%). Half of the deaths were attributable to intercurrent diseases. No toxic reactions in the lung greater than grade 3 were detected. Carbon ion beam radiotherapy with a regimen of four fractions during 1 week has been proven as a valid alternative to surgery for stage I NSCLC and to offer particular benefits, especially for elderly and inoperable patients.

Prognostic factors for survival of stage I nonsmall cell lung cancer patients

Platinum-based adjuvant chemotherapy in randomized trials has failed to provide a survival benefit in patients with resected stage I nonsmall cell lung cancer (NSCLC). Using data from the California Cancer Registry (CCR), we explored factors that had detrimental effects on survival in patients with stage I NSCLC to identify a subset of patients at high risk for disease recurrence and subsequent mortality. Between 1989 and 2003, 19,702 incident cases of stage I NSCLC in the CCR were identified and subgrouped into stage IA and IB disease. Patient demographic factors, tumor characteristics, and treatment delivered were examined. Kaplan-Meier survival curves were calculated to estimate survival rates. Cox proportional-hazards ratios were used to identify independent prognostic factors for survival. Advanced age at diagnosis, male sex, low socioeconomic status (SES), nonsurgical treatment, and poor histologic grade (stage IA NSCLC: hazards ratio [HR], 1.13; 95% confidence interval [95% CI], 1.08-1.19; stage IB NSCLC: HR, 1.11; 95% CI, 1.07-1.16) were associated with increased mortality risk on multivariate analysis. Non-upper lobe tumor location (right middle lobe, right and left lower lobes) and tumor size > or =4 cm (vs <4 cm: HR, 1.23; 95% CI, 1.15-1.30) were additional factors that increased the risk of mortality among patients with stage IB disease. Bronchioloalveolar carcinoma and Asian ethnicity were associated with decreased mortality risk in stage I NSCLC. Stage I NSCLC with poorly differentiated histology and stage IB NSCLC with non-upper lobar tumor location or tumor size > or =4 cm carried an increased mortality risk.