N0 M0 Non-small Cell Lung Cancer Research Articles

Outcomes of Patients Undergoing Segmentectomy for Occult Node-Positive Clinical Stage IA Lung Cancer

BackgroundResults of recent clinical trials suggest that segmentectomy may be an acceptable alternative to lobectomy for selected patients with early-stage non-small cell lung cancer (NSCLC). Increased use of segmentectomy may result in a concomitant increase in occult node-positive (N+) disease on surgical pathology examination. The optimal management for such patients remains unknown. MethodsClinicopathologic data were abstracted from a prospective institutional database to identify patients with pathologic N+ disease after segmentectomy for cT1 N0 M0 NSCLC. Propensity score matching identified a comparable lobectomy cohort for assessment of cumulative incidence of recurrence and overall survival (OS). ResultsOf 759 included patients, 27 (4%) had nodal upstaging on the final pathology report. Of these 27 patients, 4 (15%) had skip metastasis to N2 stations, and 20 (74%) received adjuvant therapy; no completion lobectomies were performed. Ten patients (37%) had disease recurrence: 3 isolated locoregional (11%) and 7 distant (26%). The median time to recurrence among patients with recurrence was 1.8 years; OS after recurrence was 3.4 years. After 5:1 matching with 109 patients who underwent lobectomy, all variables were balanced between the groups, except pathologic N2 stage and open surgical approach. The 5-year cumulative incidence of recurrence was not significantly different between segmentectomy and lobectomy (42% vs 52%, respectively; Gray’s P = .1). The 5-year OS (63% and 50%) and rate of locoregional recurrence (12% vs 13%) were not statistically different between the groups. ConclusionsPatients with occult N+ disease after segmentectomy for cT1 N0 M0 NSCLC had limited isolated locoregional recurrences and outcomes similar to those in patients who underwent lobectomy. Lobectomy may not provide an advantage in these patients.

Impacts of Positive Margins and Surgical Extent on Outcomes After Early-Stage Lung Cancer Resection

BackgroundSublobar resection of early-stage non-small cell lung cancer (NSCLC) is increasingly considered appropriate but may compromise margins compared with lobectomy. This study evaluated resection extent, margin status, and survival in patients with clinical stage I NSCLC. MethodsPatients with clinical T1-2 N0 M0 NSCLC in the National Cancer Database (2006-2020) who were treated with primary surgery were compared stratified by margin status. The potential benefit of radiation was explored in subgroup analysis of patients who underwent sublobar resection with positive margins. ResultsPositive margins occurred in 5089 (2.8%) of 181,824 patients and were more common in sublobar resections compared with lobectomy (4.3% vs 2.4%; P < .001). Sublobar resection had the strongest association with positive margins in multivariable analysis (odds ratio, 2.06; 95% CI, 1.91-2.23; P < .001). Patients with positive margins were more likely to undergo both adjuvant chemotherapy (16% vs 13%; P < .001) and radiation (17% vs 1%; P < .001) but had worse survival in univariate analysis (44.0% 5-year overall survival vs 69.2%; P < .001) and multivariable Cox analysis (hazard ratio, 1.71; 95% CI, 1.63-1.78; P < .001) in the entire cohort, as well as in a univariate subset analysis of lobectomy (46.9% vs 70.4%; P < .001) and sublobar resection (37.5% vs 64.1%; P < .001). Postoperative radiation for patients who underwent sublobar resection with positive margins did not improve 5-year overall survival (36.3% for irradiated patients vs 38.3% for nonirradiated patients; P = .57), and patients who underwent sublobar resection with positive margins who were treated with radiation had survival inferior to that of patients who underwent lobectomy with negative margins. ConclusionsPositive margins occur more frequently after sublobar resection of clinical stage I NSCLC compared with lobectomy. Patients with positive margins have worse survival than patients who undergo complete resection and are not rescued by postoperative radiation.

Wedge Resection Versus Segmentectomy for Older Patients With Stage IA Non-Small-Cell Lung Cancer

IntroductionAnatomic lung resection remains the standard of care for early-stage non-small-cell lung cancer (NSCLC), but wedge resection may offer similar survival in older adult patients. The objective of this study was to evaluate the survival of patients aged 80 y and older undergoing wedge resection versus segmentectomy for stage IA NSCLC using a large clinical registry. MethodsPatients aged 80 y and older in the National Cancer Database who underwent wedge resection or segmentectomy for cT1a-b N0 M0 NSCLC between 2004 and 2018 were identified for an analysis. Survival was assessed using multivariable Cox proportional hazards analysis, propensity-score matching, and inverse probability weighting. A subgroup analysis of patients who underwent lymph node evaluation with their wedge resection or segmentectomy was also performed. ResultsOf the 2690 patients identified, 2272 (84%) underwent wedge resection and 418 (16%) underwent segmentectomy. Wedge resection was associated with worse 5-year overall survival relative to segmentectomy in multivariable-adjusted (adjusted Hazard Ratio: 1.26, [1.06-1.51], P = 0.01) and propensity score-matched analysis (49% [95% confidence interval {CI}: 42%-55%] versus 59% [95% CI: 52%-65%], P = 0.02). Among a subgroup of 1221 wedge resection and 347 segmentectomy patients who also received intraoperative lymph node evaluation, however, there were no significant differences in 5-year survival in multivariable-adjusted (adjusted Hazard Ratio: 1.12, [0.90-1.39], P = 0.31) or propensity score-matched analysis (55% [95% CI: 48%-62%] versus 61% [95% CI: 54%-68%], P = 0.10). ConclusionsIn this national analysis, there were no significant differences in survival between older adult patients with stage IA NSCLC who underwent wedge resection versus segmentectomy when a lymph node evaluation was performed.

Lobectomy versus segmentectomy in patients with stage T (> 2 cm and ≤ 3 cm) N0M0 non-small cell lung cancer: a propensity score matching study

BackgroundThe safety and effectiveness of lung segmentectomy in patients with early non-small cell lung cancer (NSCLC) remains controversial. We have therefore reviewed the clinicopathologic characteristics and survival outcomes of patients treated with lobectomy or segmentectomy for early T (> 2 and ≤ 3 cm) N0M0 NSCLC.MethodsWe obtained data from the Surveillance, Epidemiology, and End Results database for patients who underwent lobectomy or segmentectomy between 2004 and 2015. To reduce bias and imbalances between the treatment groups, propensity score matching analysis was performed. We used Kaplan–Meier curves to estimate overall survival (OS) and lung cancer-specific survival (LCSS). We conducted univariate and multivariate Cox proportional hazards regression analyses to identify independent prognostic factors for OS and cancer-specific survival, and applied the Cox proportional hazards model to create forest plots.ResultsBefore matching, both univariate and multivariate Cox regression analyses revealed that patients who underwent lobectomy exhibited better OS (P < 0.001) and LCSS (P = 0.001) than patients who underwent segmentectomy. However, after matching, survival differences between the groups were not significant; OS (P = 0.434) and LCSS (P = 0.593). Regression analyses revealed that age and tumor grade were independent predictors of OS and LCSS (P < 0.05).ConclusionsPatients with stage T (> 2 and ≤ 3 cm) N0M0 NSCLC undergoing segmentectomy can obtain OS and LCSS similar to those obtained with lobectomy. Further studies are required considering the solid component effects and pathologic tumor types regarding segmentectomies. Additional long-term survival and outcome analyses should be conducted with larger cohorts.

Surgical Outcomes for Early-Stage Non-Small Cell Lung Cancer at Facilities With Stereotactic Body Radiation Therapy Programs

<h3>Purpose/Objective(s)</h3> Patients undergoing surgery for early-stage non-small cell lung cancer (NSCLC) may be at high-risk for post-operative mortality. Access to stereotactic body radiation therapy (SBRT), a less invasive alternative, may facilitate more appropriate patient selection for surgery. <h3>Materials/Methods</h3> An analysis of all patients with early-stage NSCLC reported to the National Cancer Database between 2004-2015 was performed. Post-operative mortality rates were derived using vital status data. Utilization of SBRT was defined by each facility's SBRT Experience in years and SBRT-to-Surgery Volume Ratios, defined by quartiles. Multivariable logistic regression with backward elimination was used to test for the associations between facility-level SBRT utilization and post-operative mortality. Interaction testing of independent covariates was performed to assess the effect of SBRT utilization across subgroups. <h3>Results</h3> The study cohort consisted of 202,542 patients who underwent surgical resection of clinical stage T1-T2 N0 M0 NSCLC between 2004-2015. The 90-day post-operative mortality rate declined significantly during the study period from 4.6% to 2.6% (p < 0.001). During this period, the proportion of facilities that utilized SBRT increased from 4.6% to 77.5% (p < 0.001) and the proportion of patients treated with SBRT increased significantly from 0.7% to 15.4% (p < 0.001). On multivariable analysis, lower 90-day post-operative mortality rates were observed among patients who underwent resection at facilities with greater than six years of SBRT Experience (OR 0.84, CI 0.76-0.94, p = 0.003) and SBRT-to-Surgery Volume Ratios above 17% (OR 0.85, CI 0.79-0.92, p < 0.001). Additional covariates associated with 90-day mortality included higher surgical volume, geographic region, year of diagnosis, age, sex, race, insurance status, facility type, Charlson-Deyo score, clinical T stage, histology, anatomic location, surgery type, and prior malignancy. Interaction testing between these covariates was negative, demonstrating that findings were consistent across subgroups. <h3>Conclusion</h3> Patients who underwent surgical resection for early-stage NSCLC at facilities with higher SBRT Experience and SBRT-to-Surgery Volume Ratios had lower rates of post-operative mortality. These findings suggest that the availability of SBRT may improve allocation of patients to surgery or SBRT, particularly for higher-risk patients. The observation of higher post-operative mortality rates at facilities without an SBRT program merits further investigation.

Image-Guided Hypofractionated Proton Therapy in Early-Stage Non-Small Cell Lung Cancer: A Phase 2 Study.

PurposeDue to the excellent outcomes with image-guided stereotactic body radiotherapy for patients with early-stage non–small cell lung cancer (NSCLC) and the low treatment-related toxicities using proton therapy (PT), we investigated treatment outcomes and toxicities when delivering hypofractionated PT.Materials and MethodsBetween 2009 and 2018, 22 patients with T1 to T2 N0M0 NSCLC (45% T1, 55% T2) received image-guided hypofractionated PT. The median age at diagnosis was 72 years (range, 58-90). Patients underwent 4-dimensional computed tomography simulation following fiducial marker placement, and daily image guidance was performed. Nine patients (41%) were treated with 48 GyRBE in 4 fractions for peripheral lesions, and 13 patients (59%) were treated with 60 GyRBE in 10 fractions for central lesions. Patients were assessed for CTCAEv4 toxicities with computed tomography imaging for tumor assessment. The primary endpoint was grade 3 to 5 toxicity at 1 year.ResultsThe median follow-up for all patients was 3.5 years (range, 0.2-8.8 years). The overall survival rates at 3 and 5 years were 81% and 49%, respectively. Cause-specific survival rates at 3 and 5 years were 100% and 75%, respectively. The 3-year local, regional, and distant control rates were 86%, 85%, and 95%, respectively. Four patients experienced in-field recurrences between 18 and 45 months after treatment. One patient (5%) developed a late grade 3 bronchial stricture requiring hospitalization and stent.ConclusionImage-guided hypofractionated PT for early-stage NSCLC provides promising local control and long-term survival with a low likelihood of toxicity. Regional nodal and distant relapses remain a problem.

Intentional Segmentectomy for Clinical T1 N0 Non-small Cell Lung Cancer: Survival Differs by Segment

Outcomes after segmentectomy compare favorably with those after lobectomy in patients with stage I non-small cell lung cancer (NSCLC). Whether long-term outcomes vary by segmentectomy location is unclear. We investigated whether disease-free survival (DFS) and overall survival (OS) differ by segmentectomy location after intentional segmentectomy for clinical T1 N0 M0 NSCLC. Patients who received intentional segmentectomy for cT1 N0 M0 NSCLC from 2000 to 2018 were reviewed. Patients with prior lung cancer, forced expiratory volume in 1 second of less than 50%, or R1/R2 resection were excluded. Segmentectomy groups were left (L) basilar, L segment 6, L lingula, L trisegment; right (R): basilar (R_Bas), segment 6 (R_S6), and R upper. The 5- and 10-year DFS and OS were estimated using Kaplan-Meier and compared between groups using the log-rank test. Factors associated with DFS and OS were determined using Cox proportional hazards models. In total, 416 patients met the inclusion criteria. Segmentectomy groups differed with regard to surgical approach, mediastinal lymphadenectomy, lymphovascular invasion, tumor histology, margin distance, and adjuvant therapy. Long-term outcomes were worst after R_S6 resection (5-year DFS, 57.6% [95% confidence interval {CI}, 45.7%-72.7%]; OS, 66.3% [95% CI, 54.7%-80.3%]) and best after R_Bas resection (5-year DFS, 77.1% [95% CI, 59.2%-100%]; OS, 79.5% [95% CI, 60.9%-100%]). On multivariable analysis, R_S6 resection was independently associated with DFS vs R_Bas (hazard ratio, 2.89; 95% CI, 1.18-7.08; P= .02) and OS vs R_Bas (hazard ratio, 4.35; 95% CI, 1.61-11.76; P= .004). Resection of R_S6 is independently associated with worse DFS and OS in patients receiving intentional segmentectomy for cT1 N0 M0 NSCLC and may warrant more extensive resection, complete lymph node dissection, and closer postoperative surveillance.

Long-Term Prognosis After Segmentectomy for cT1 N0 M0 Non-Small Cell Lung Cancer

Prognosis beyond 5 years after segmentectomy for non-small cell lung cancer (NSCLC) has not been well studied. This study is a retrospective analysis of a previous prospective cohort study of patients with peripheral cT1 N0 M0 NSCLC who underwent segmentectomy between 2005 and 2009. Exclusion criteria were right middle lobe tumors, multiple tumors in same lobe, patients having considerable risk for segmentectomy, and patients requesting lobectomy rather than segmentectomy. The median follow-up period was 108 months. Study outcomes included overall survival, recurrence-free probability, and local recurrence. Of 179 patients with cT1 N0 M0 who were treated by segmentectomy, clinical T stages were Tis in 57 patients, T1mi or T1a in 34, T1b in 57, and T1c in 31. All tumors were pathologic N0 tumors. The 10-year recurrence-free probability rates in each clinical stage were 100% in Tis,97% in T1mi or T1a, 90% in T1b, and 69% in T1c, which were significantly lower in advanced T stages (p < 0.001). Fourteen patients (8%) experienced recurrences after segmentectomy; these were local in 8 patients (five recurrences at the surgical margin and three in the preserved lobe) and nonlocal in 6patients. Six of the eight local recurrences developed morethan 5 years after segmentectomy. All eight local recurrences were treated by local therapy, resulting in 6 patients surviving without disease at 55 months of median follow-up after the additional treatments. Although segmentectomy may be a viable curative option for treating T1 N0 M0 NSCLC, monitoring for local recurrence should be continued beyond 5 years after segmentectomy to avoid missing opportunities to effect a cure.

Radiation to the Immune System May be an Important Risk Factor for Long-term Survival after SBRT in Early Stage Non-small Cell Lung Cancer: A Role of RT Plan Optimization

Stereotactic body radiation therapy (SBRT) is the treatment of choice in patients with early stage inoperable non-small cell lung cancer (NSCLC). Local tumor control after SBRT is outstanding; however, 5-year overall survival rates remain suboptimal at less than 50%, which cannot be fully explained by known etiologies such as comorbidity, distant cancer progression or conventional toxicity. We hypothesize that radiation to normal tissue, particularly the sensitive lymphocytes in the immune system, contribute to the poor survival in these patients. Patients with T1-T2 N0 M0 NSCLC who received SBRT without previous RT and had retrievable radiotherapy (RT) plans in our modern treatment planning system were eligible. The primary endpoint was overall survival, calculated from the start of SBRT. Clinical factors included age, gender, race, tobacco history, respiratory and cardiovascular comorbidity, tumor lobar location, histology, T stage, gross tumor volume (GTV), planning target volume (PTV), and prescription dose BED10. Heart and lung were contoured consistently by one radiation oncologist according to the RTOG atlas. Effective dose to lymphocytes were computed by an in-house model. A total of 280 patients met criteria. The median follow-up was 6.7 years. The median survival time was 33 months (95% CI: 25-42 months). The 2-year, 3-year and 5-year survival rates were 63%, 53% and 45%, respectively. Univariate analysis demonstrated that age (HR=1.02, p=0.04), gender (HR=0.75 for female, p=0.07), tumor T stage (HR=1.3 for T2, 2.5 for T3, using T1 as the reference, p=0.10), KPS(HR=0.97, p<0.001), GTV (HR=1.01, p<0.001), PTV (HR=1.01, p<0.001), mean lung dose (HR=1.2, p<0.001), mean heart dose (HR=1.001, p=0.029) and EDIC were all significantly associated with overall survival. Multivariate analysis demonstrated KPS, GTV, mean lung dose, mean heart dose and EDIC were all significant as continuous variables, but only KPS, GTV, EDIC remained. A 1 Gy increase in EDIC was associated with a 46 % increase in the risk of death, or 20% reduction in 5-year survival. This study is the first to demonstrate that radiation dose to lung, heart and lymphocytes are independent factors predicting long-term overall survival after SBRT. These findings suggests that the poor survival after SBRT is likely at least in part from damage to radiation-sensitive lymphocytes and may suggest an area of further plan optimization during SBRT practice.

SUNSET: Stereotactic Radiation for Ultracentral Non–Small-Cell Lung Cancer—A Safety and Efficacy Trial

BackgroundLung stereotactic body radiotherapy (SBRT) is considered a standard curative treatment for medically inoperable early stage non–small-cell lung cancer (NSCLC). Patients with ultracentral tumors (signifying tumors whose planning target volume touches or overlaps the central bronchial tree, esophagus, or pulmonary artery) may be at higher risk of serious toxicities such as bronchial stricture and collapse, esophageal strictures, tracheal–esophageal fistula, and hemorrhage. The primary objective of the study is to determine the maximum tolerated dose of radiotherapy for ultracentral NSCLC. MethodsThis multicenter phase 1 dose-escalation study will use a time-to-event continual reassessment method (TITE-CRM). Accrual will start at level 1 (60 Gy in 8 fractions delivered daily). The model will use all available information from previously accrued patients to assign the highest dose with a predicted risk of grade 3-5 toxicity of 30% or less. All patients with newly diagnosed stage T1-3 N0M0 NSCLC (International Union Against Cancer, 8th edition) with tumor size ≤ 6 cm and meeting the criteria for ultracentral location (ie, tumors whose planning target volume touches or overlaps the central bronchial tree, esophagus, pulmonary vein, or pulmonary artery) will be eligible for this study. DiscussionIt is important to identify a safe dose-fractionation regimen for treating ultracentral tumors with SBRT. In addition, the data from this study may be informative in guiding future studies on the use of SBRT in treating malignancies within the mediastinum—for example, for salvage treatment of mediastinal lymph nodes for recurrent NSCLC or mediastinal oligometastases.

Influence of Fractionation Scheme and Tumor Location on Toxicities After Stereotactic Body Radiation Therapy for Large (≥5 cm) Non-Small Cell Lung Cancer: A Multi-institutional Analysis

Todescribe the impact of fractionation scheme and tumor location on toxicities in stereotactic body radiation therapy (SBRT) for ≥5-cm non-small cell lung cancer (NSCLC), as part of a multi-institutional analysis. Patients with primary ≥5-cm N0 M0 NSCLC who underwent ≤5-fraction SBRT were examined across multiple high-volume SBRT centers. Collected data included clinical/treatment parameters; toxicities were prospectively assessed at each institution according to the Common Terminology Criteria for Adverse Events. Patients treated daily were compared with those treated every other day (QOD)/other nondaily regimens. Stratification between central and peripheral tumors was also performed. Ninety-two patients from 12 institutions were evaluated (2004-2016), with median follow-up of 12months. In total there were 23 (25%) and 6 (7%) grade ≥2 and grade ≥3 toxicities, respectively. Grades 2 and 3 pulmonary toxicities occurred in 9% and 4%, respectively; 1 patient treated daily experienced grade 5 radiation pneumonitis. Of the entire cohort, 46 patients underwent daily SBRT, and 46 received QOD (n=40)/other nondaily (n=6) regimens. Clinical/treatment parameters were similar between groups; the QOD/other group was more likely to receive 3-/4-fraction schemas. Patients treated QOD/other experienced significantly fewer grade ≥2 toxicities as compared with daily treatment (7% vs 43%, P<.001). Patients treated daily also had higher rates of grade ≥2 pulmonary toxicities (P=.014). Patients with peripheral tumors (n=66) were more likely to receive 3-/4-fraction regimens than those with central tumors (n=26). No significant differences in grade ≥2 toxicities were identified according to tumor location (P>.05). From this multi-institutional study, toxicity of SBRT for ≥5-cm lesions is acceptable, and daily treatment was associated with a higher rate of toxicities.

Impact of whole tumor size in part-solid non-small cell lung cancer

In the recent issue of Annals of Thoracic Surgery, Hattori et al . reported the impact of the maximum tumor size and solid component size on the prognosis of patients with non-small cell lung cancer (NSCLC) (1). They evaluated 1,181 surgically resected cases of clinical N0 M0 NSCLC. The patients were divided into three groups according to the radiologically determined consolidation tumor ratio (CTR): the pure ground-glass opacity (GGO) group (CTR =0; n=168), the part-solid (0<CTR<1; n=448) group and the solid (CTR =1; n=565) group. The authors reported that the tumor size had a significantly impact on the 5-year overall survival (OS) of patients with radiologically solid tumors (≤20 mm, 83%; 21–30 mm, 75.4%; 31–50 mm, 56.2%; ≥51 mm, 45.3%; P<0.0001). In contrast, the tumor size did not influence the 5-year OS of patients with radiologically pure GGOs (100%, regardless of the tumor size) or part-solid tumors (≤20 mm, 97.7%; 21–30 mm, 94.6%; 31–50 mm, 93.4%; P=0.1028). In addition, the size of the solid component and CTR were not associated with OS in patients with part-solid tumor. They therefore concluded that the impact of maximum tumor size should only be applied to radiologically solid lung cancer (1).

Lobectomy Versus Segmentectomy in Radiologically Pure Solid Small-Sized Non-Small Cell Lung Cancer

The indication for limited resection of radiologically pure solid non-small cell lung cancer (NSCLC) is controversial owing to its invasive pathologic characteristics. This study was performed to compare the outcomes after lobectomy and segmentectomy in these NSCLC patients. We retrospectively reviewed 251 patients with radiologically pure solid cT1a N0 M0 NSCLC who underwent lobectomy or segmentectomy, and the preoperative characteristics of the patients treated with the two operative techniques were matched using propensity score methods. Overall survival (OS) and disease-free survival (DFS) curves were compared using the log rank test, and differences in survival were also evaluated by the McNemar test. The preoperative factors and surgical procedure were analyzed with the multivariate Cox proportional hazards regression model to identify independent predictors of poor OS and DFS. In the propensity score matched lobectomy and segmentectomy groups (87 patients per group), the 5-year and 10-year OS rates were 85% versus 84% and 66% versus 63%, respectively; and the 5-year and 10-year DFS rates were 80% versus 77% and 64% versus 58%, respectively. There were no significant differences between the two groups in OS or DFS by the log rank test, and also no significant differences in 3-year, 5-year, or 7-year OS or DFS by the McNemar test. Although age, smoking status, pulmonary function, and carcinoembryonic antigen were identified as significant predictors of both OS and DFS, the surgical procedure was not identified. Similar oncologic outcomes after lobectomy and segmentectomy were indicated among patients with radiologically pure solid small-sized NSCLC.

Oncologic Outcomes of Segmentectomy Versus Lobectomy for Clinical T1a N0 M0 Non-Small Cell Lung Cancer

We retrospectively compared the oncologic outcome after segmentectomy versus lobectomy in patients with clinical (c-) T1a N0 M0 non-small cell lung cancer (NSCLC) detected as a part-solid ground-glass nodule or purely solid nodule on thin-section computed tomography. From 1997 to 2010, 312 patients with c-T1a N0 M0 NSCLC were determined to require a surgical approach categorized as segmentectomy or lobectomy. Preoperatively available data were collected using logistic regression analysis, and propensity matching was performed. Factors affecting local-regional recurrence were assessed by Cox proportional hazards regression analysis and Kaplan-Meier estimates. The 5-year and 10-year overall survival rates for the 80 patients who underwent segmentectomy were 97.5% and 83.5%, respectively, compared with 87.75% and 75.0%, respectively, for the 232 patients who underwent lobectomy (p= 0.019). Local-regional recurrence as the first relapse site was found in 3 the 80 segmentectomies (3.8%) of and in 15 of the 232 lobectomies (6.5%). The difference in local-regional recurrence-free survival in patients undergoing segmentectomy compared with lobectomy was not significant (p= 0.304). In 69 propensity score-matched pairs, there was no significant difference in the overall survival (p= 0.442) or local-regional recurrence-free survival (p= 0.717) between the two groups. Multivariate analysis using the Cox proportional hazards regression model identified lymphatic invasion as the only independent factor predicting local-regional recurrence (relative risk, 10.764; 95% confidence interval, 2.98 to 57.68). Our results suggest that the oncologic outcome of segmentectomy vs lobectomy is similar in thiscohort of c-T1a N0 M0 NSCLC patients. These results will be validated by large-scale, prospective, randomized trials.

Sublobar resection is equivalent to lobectomy for T1a non–small cell lung cancer in the elderly: a Surveillance, Epidemiology, and End Results database analysis

BackgroundAnatomic lobectomy with mediastinal lymph node dissection is considered the optimal management for early stage non–small cell lung cancer (NSCLC). Limited lung resection may be preferable in the elderly population, who are more likely to have poor pulmonary reserve and multiple comorbidities. Our primary objective was to compare the survival of patients aged ≥75 y who underwent sublobar resection or lobectomy for stage IA NSCLC. Materials and methodsWe queried the Surveillance, Epidemiology, and End Results database for patients aged ≥75 y who were diagnosed with stage IA NSCLC from 1998–2007. Patients were divided into three groups based on the type of surgery performed (wedge resection, segmentectomy, and lobectomy). Kaplan–Meier analysis and Cox proportional hazard model were used for survival analysis. ResultsA total of 1640 patients were analyzed. Lobectomy was performed in 1051 patients, 119 underwent segmentectomy, and 470 patients had wedge resection. Overall and cancer-specific survival were significantly lower in the wedge resection group as compared with those in lobectomy (P < 0.05). However, for T1a tumors, no significant difference was found in risk adjusted 5-y cancer-specific survival for patients who underwent wedge resection, segmentectomy (hazard ratio, 1.009; 95% confidence interval 0.624–1.631; P = 0.972), or lobectomy (hazard ratio, 0.98; 95% confidence interval, 0.691–1.388; P = 0.908). ConclusionsSublobar resection is not inferior to lobectomy for T1a N0 M0 NSCLC in the elderly and should be considered a viable alternative in this high-risk population.

Évaluation radiologique de la réponse tumorale après radiothérapie pulmonaire en conditions stéréotaxiques

Stereotactic body radiotherapy is the treatment of choice for medically non-operable T1-T2 N0M0 non-small cell lung cancer or for slowly growing lung metastases with no evolutive primary tumour. Lung stereotactic radiotherapy provides an excellent local control rate, higher than 80%. Nevertheless, although the clinical toxicity rate is less than 5%, postradiation radiological reactions surrounding the tumour, called “radiological radiation pneumonitis”, are very frequent, which makes it difficult to evaluate the tumour response. Firstly, this review describes the lesions of acute and chronic radiation pneumonitis and the CT images suggesting a local recurrence. Then, we evaluated the place of PET after stereotactic body radiotherapy in the follow-up period. Finally, we suggest an algorithm helping physicians in the follow-up of such treated patients.

Visceral Pleural Invasion Is Not Predictive of Survival in Patients With Lung Cancer and Smaller Tumor Size

Visceral pleural invasion (VPI) is used as an indicator of adverse prognosis in non-small cell lung cancer (NSCLC). The purpose of this retrospective study was to evaluate the impact of VPI on disease-free survival (DFS) and overall survival (OS) in patients with node-negative NSCLC. Between 1998 and 2009, 1,166 patients with pathologic N0M0 NSCLC underwent surgical resection by lobectomy. Two hundred fourteen patients with VPI were compared with 952 patients without VPI. Median follow-up was 59 months. In multivariate analysis, VPI, larger tumor size, older age, female sex, and poor performance status were significantly associated with decreased OS. In contrast, larger tumor size, female sex, and poor performance, but notably not VPI, were associated with decreased DFS. After examining interactive effects of VPI and T stage subgroups, we found that VPI did not significantly affect either OS or DFS in the subgroups of patients with smaller tumor sizes-stage T1a, stage T1b, or stage T2a. In contrast, a deleterious effect of VPI on DFS was seen for tumors larger than 5 cm-stages T2b and T3-with the VPI-stage T3 interaction effect being statistically significant for DFS but not for OS. The effect of VPI on survival in NSCLC varies greatly with tumor size, with VPI not strongly associated with OS or DFS in tumors smaller than 5 cm, but showing large negative effects on DFS for stage T2b and stage T3 tumors. Using VPI to upstage T1 tumors to a higher T stage is not warranted because it would misrepresent these VPI-T stage subgroup effects.

Comparison of lobe-specific mediastinal lymphadenectomy versus systematic mediastinal lymphadenectomy for clinical stage T 1a N 0 M 0 non-small cell lung cancer

This study was to explore the appropriate extent of mediastinal lymph node dissection for clinical stage T₁a N₀ M₀ non-small cell lung cancer (NSCLC) by comparison between two modes of mediastinal lymph node dissection. A total of 96 clinical stage T₁a N₀ M₀ NSCLC cases received radical surgery were randomly divided to lobe-specific mediastinal lymphadenectomy (LL) group and systematic mediastinal lymphadenectomy (SL) group from the year 2004 to 2008. The effects of SL and LL on morbidity, N staging, overall survival (OS) and disease-free survival (DFS) were investigated. Meanwhile, associations between clinicopathological parameters and metastasis of lymph nodes were analyzed. The mean operating time and blood loss in LL group were significantly less than that in the SL group (135.48 ± 25.44 min vs. 180.85 ± 39.36 min, 155.11 ± 25.17 ml vs. 161.32 ± 28.20 ml, P < 0.05), the mean numbers of dissected lymph nodes of the SL group was significantly greater than that in the LL group (17.1 ± 3.7 vs. 9.4 ± 2.1, P < 0.05). The post-operative overall morbidity rate was higher in the SL group than that in the LL group (P < 0.05). There were no significant difference in migration of N staging, OS and DFS between two groups. The post-operative N staging, the tumor cells differentiation and the ratio of ground glass opacity (GGO) in tumor were the independent factors influencing long-term survival. Moreover, the significant correlation was seen between the metastasis of lymph nodes and clinicopathological parameters including tumor location and the GGO ratio. The LL group had similar efficacy as the SL group in the clinical stage T₁a N₀ M₀ NSCLC and there was unnecessary to perform systematic lymphadenectomy in such patients with a high ratio of GGO.

Postoperative follow-up of lung cancer: Randomized trial comparing two follow-up programs in completely resected non-small cell lung cancer (IFCT-0302).

TPS7111 Background: There are no robust data published on the follow-up after surgery for non-small cell lung cancer (NSCLC). Current international guidelines are informed by expert opinion. Most of them recommend regular follow-up with clinic visit and thoracic imaging, either chest X-ray of Chest CT-scan. The IFCT-0302 trial addresses the question whether a surveillance program with chest CT-scan and fiberoptic bronchoscopy can improve survival compared to a follow-up only based on physical examination and chest x-ray. There is no such trial ongoing over the world. Methods: The IFCT-0302 trial is a multicenter open-label controlled randomized phase III trial. The objective of the trial is to compare two follow-up programs after surgery for stage I-IIIa NSCLC. The primary endpoint is overall survival. Patients are randomly assigned to arm 1, minimal follow-up, including physical examination and chest x-ray; or arm 2, a follow-up consisting of physical examination and chest x-ray plus chest CT scan and fiberoptic bronchoscopy (optional for adenocarcinomas). In both arms, follow-up procedures are performed every 6 months during the first two postoperative years, and every year between the third and the fifth years. The main eligibility criteria include: completely resected stage I-IIIA (6th UICC TNM classification) or T4 (in case of nodules in the same lobe as the tumor) N0 M0 NSCLC, surgery within the previous 8 weeks. Patients who have received and/or who will receive pre/post-operative chemotherapy and/or radiotherapy are eligible. Statistical considerations: 1,744 patients is required. Accrual status: 1,568 patients from 119 French centers had been included. The end of accrual can be expected for September 2012. Ancillary study: Blood samples are collected in 1000 patients for genomic high density SNP micro-array analysis. This collection will contribute to the French genome wide association study (gwas) of lung cancer gene susceptibility, and the genetic factors predictive of survival and lung cancer recurrence will be analyzed.

Is completion lobectomy merited for unanticipated nodal metastases after radical segmentectomy for cT1 N0 M0/pN1-2 non–small cell lung cancer?

To examine the role of radical segmentectomy, defined as a segmentectomy with extensive hilar/mediastinal lymph node dissection and a sufficient surgical margin, for local control in cT1 N0 M0/pN1-2 non-small cell lung cancer (NSCLC), we examined the following: (1) whether metastases were observed in specimens additionally resected by completion lobectomy undertaken after segmentectomy because of pN1-2 disease and (2) prognostic outcome in patients whose operations were completed with segmentectomy regardless of pN1-2. Of 275 patients with cT1 N0 M0 NSCLC who were scheduled to undergo radical segmentectomy, 15 (6%) had a diagnosis of pN1 or N2 disease. Of these patients, 10 were additionally treated with completion lobectomy, whereas the operations of the remaining 5 were completed with segmentectomy. None of the 10 patients who underwent completion lobectomy showed residual metastases in the specimens additionally resected by completion lobectomy. Two of the 5 patients whose operations were completed with segmentectomy, regardless of N1 or N2 disease, had tumor recurrence, but their first recurrence was not local. Radical segmentectomy, with extensive hilar/mediastinal lymph node dissection and a sufficient surgical margin, may play a role in local control in patients with cT1 N0 M0/pN1-2 NSCLC.