T1N0M0 Non-small Cell Lung Cancer Research Articles

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.

No prognostic impact of staging bone scan in patients with stage IA non-small cell lung cancer.

To investigate the survival benefit of preoperative bone scan in asymptomatic patients with early-stage non-small cell lung cancer (NSCLC). This retrospective study included patients with radical resection for stage T1N0M0 NSCLC between March 2013 and December 2018. During postoperative follow-up, we monitored patient survival and the development of bone metastasis. We compared overall survival, bone metastasis-free survival, and recurrence-free survival in patients with or without preoperative bone scan. Propensity score matching and inverse probability of treatment weighting were used to minimize election bias. A total of 868 patients (58.19 ± 9.69years; 415 men) were included in the study. Of 87.7% (761 of 868) underwent preoperative bone scan. In the multivariable analyses, bone scan did not improve overall survival (hazard ratio [HR] 1.49; 95% confidence intervals [CI] 0.91-2.42; p = 0.113), bone metastasis-free survival (HR 1.18; 95% CI 0.73-1.90; p = 0.551), and recurrence-free survival (HR 0.89; 95% CI 0.58-1.39; p = 0.618). Similar results were obtained after propensity score matching (overall survival [HR 1.28; 95% CI 0.74-2.23; p = 0.379], bone metastasis-free survival [HR 1.00; 95% CI 0.58-1.72; p = 0.997], and recurrence-free survival [HR 0.76; 95% CI 0.46-1.24; p = 0.270]) and inverse probability of treatment weighting. There were no significant differences in overall survival, bone metastasis-free survival, and recurrence-free survival between asymptomatic patients with clinical stage IA NSCLC with or without preoperative bone scan.

Time between imaging and surgery is not a risk factor for upstaging of clinical stage IA non-small-cell lung cancer.

The timing of preoperative imaging in patients with lung cancer is a debated topic, as there are limited data on cancer progression during the interval between clinical staging by imaging and pathological staging after resection. We quantified disease progression during this interval in patients with early stage non-small-cell lung cancer (NSCLC) to better understand if its length impacts upstaging. We retrospectively reviewed our institutional database to identify patients who underwent surgery for clinically staged T1N0M0 NSCLC from January 2015 through September 2022. Tumour upstaging between chest computed tomography (CT) and surgery were analysed as a function of time (<30, 30-59, ≥60 days) for different nodule subtypes. We analysed data across 3 timeframes using Pearson's chi-squared and analysis of variance tests. During the study period, 622 patients underwent surgery for clinically staged T1N0M0 NSCLC. CT-to-surgery interval was <30 days in 228 (36.7%), 30-59 days in 242 (38.9%) and ≥60 days in 152 (24.4%) with no differences in patient or nodule characteristics observed between these groups. T-stage increased in 346 patients (55.6%) between CT imaging and surgery. Among these patients, 126 (36.4%) had ground-glass nodules, 147 (42.5%) had part-solid nodules and 73 (21.1%) had solid nodules. CT-to-surgery interval length was not associated with upstaging of any nodule subtype (full-cohort, P = 0.903; ground-glass, P = 0.880; part-solid, P = 0.858; solid, P = 0.959). This single-centre experience suggests no significant association between tumour upstaging and time from imaging to lung resection in patients with clinical stage IA NSCLC. Further studies are needed to better understand the risk factors for upstaging.

Assessing Patterns of Practice in Early-Stage Lung Cancer Radiation Therapy: Findings from a Large Statewide Consortium Study on Hypofractionation

There are many different acceptable radiation dose and fractionation regimens for the treatment of early-stage non-small cell lung cancer (NSCLC), including hypofractionation (HypoRT). There are limited data supporting when to use HypoRT. We investigated which factors led physicians to choose HypoRT rather than stereotactic body radiation therapy (SBRT) or conventional fractionation (CRT) for early-stage NSCLC patients in a statewide consortium. We examined patients with T1-3N0M0 NSCLC treated at multiple institutions in a statewide consortium from January 2012-July 2022. We classified treatments as SBRT if 5 fractions or fewer, HypoRT if 6-20 fractions, and CRT if 1.8-2 Gy per fraction (Gy/Fx) for 25 or greater fractions. We excluded patients between 20 and 25 fractions as most appeared to be CRT that did not finish treatment (5% of total). We then performed a classification tree using age, race, gender, smoking status, T stage, PTV within 2cm of esophagus, PTV within 2cm of heart, and concurrent chemotherapy as covariates with a three-variable output (SBRT, HypoRT, and CRT). We excluded ECOG as it was not significant on initial analysis and was missing for 100 patients. We also reran the classification tree without CRT as an output to better discriminate between SBRT and HypoRT. A total of 418 patients were included in the analysis. 184 patients had T1, 123 with T2, and 111 with T3 tumors. In total, 228 patients underwent SBRT (median 50 Gy), 51 patients HypoRT (median 60 Gy), and 139 CRT (median 63 Gy). Covariates significant for discriminating between all three treatment regimens included T2, T3 vs T1, PTV within 2cm of the esophagus, and T3 vs T2. 94% of T1 patients were treated with SBRT. Among T2 and T3 patients, those within 2cm of the esophagus were significantly more likely to be treated with CRT or HypoRT (80% vs 15%). Patients with T3 tumor not within 2cm of the esophagus, were more likely to be treated with CRT or HypoRT than the T2 patients (85% vs 36%). Patients treated with CRT were also more likely to receive chemotherapy, particularly for T3 tumors (80% received concurrent chemotherapy). Excluding CRT as an output variable, proximity to the heart became significant in addition to the other previously described covariates. Notably, the branch with the highest likelihood of HypoRT were patients with T2/T3 tumors within 2 cm of both the esophagus and heart (94% HypoRT vs 6% SBRT). Patients with tumors not close to central structures but with T3 rather than T2 tumors were more likely to be treated with HypoRT as well (62% vs 38%). Based on this large prospective real-world data of early-stage NSCLC, larger tumors and those located near central structures are more likely to be treated with HypoRT. The patient's age, performance status, race, and smoking status were not significant in this analysis. Additional analysis on outcomes and toxicity related to treatments is underway.

Change in Quality of Life after Stereotactic Body Radiation Therapy (SBRT) on a Prospective Trial of Peripheral Stage I or II Non-Small Cell Lung Cancer Predicts Survival

We previously reported the results of a randomized, multi-institutional phase II clinical trial evaluating one versus three fractions of SBRT for peripheral Stage I to II non-small cell lung cancer (NSCLC). A secondary objective to compare quality of life (QOL) data and its association with survival outcomes is reported. Medically inoperable patients with biopsy-proven peripheral T1-2N0M0 NSCLC were enrolled. Patients were randomized to 30 Gy in 1 fraction (arm 1) or 60 Gy in 3 fractions (arm 2) and stratified by performance status. QOL scores from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and EORTC QLQ Lung Cancer-Specific Module (EORTC QLQ-LC13) questionnaires were required at baseline and each follow-up visit. Univariate models were generated to evaluate associations between QOL scores and survival with 95% confidence intervals (CI) calculated at each time point. Among 98 patients enrolled (49 in each arm), 88 patients had data available for QOL analysis. At 6 month follow up, patients with stable or decreased (n = 49) versus those with increased global QOL scores (n = 27) had worse progression-free survival (HR [Hazards' Ratio] 2.32 [CI, 1.14-4.73], p = 0.021) and overall survival (HR 2.13 [CI, 1.01-4.51], p = 0.048). Similar results persisted at the 12 month follow up for progression-free survival (HR 3.90 [CI, 1.52-10.04], p = 0.016) and overall survival (HR 3.25 [CI, 1.25-8.43], p = 0.016). Median overall survival for patients with stable or decreased global QOL versus increased global QOL at 6 month follow up was 39.0 vs 60.3 months (p = 0.032). Change in QOL is an early predictor of survival following SBRT for patients with peripheral early-stage NSCLC.

Development and validation of prognostic nomogram for T1-3N0M0 non-small cell lung cancer after curative resection

BackgroundRadical resection plus lymph node dissection is a common treatment for patients with T1-3N0M0 non-small cell lung cancer (NSCLC). Few models predicted the survival outcomes of these patients. This study aimed to developed a nomogram for predicting their overall survival (OS).Materials and methodsThis study involved 3002 patients with T1-3N0M0 NSCLC after curative resection between January 1999 and October 2013. 1525 Patients from Sun Yat-sen University Cancer Center were randomly allocated to training cohort and internal validation cohort in a ratio of 7:3. 1477 patients from ten institutions were recruited as external validation cohort. A nomogram was constructed based on the training cohort and validated by internal and external validation cohort to predict the OS of these patients. The accuracy and practicability were tested by Harrell's C-indexes, calibration plots and decision curve analyses (DCA).ResultsAge, sex, histological classification, pathological T stage, and HI standard were independent factors for OS and were included in our nomogram. The C-index of the nomogram for OS estimates were 0.671 (95% CI, 0.637–0.705),0.632 (95% CI, 0.581–0.683), and 0.645 (95% CI, 0.617–0.673) in the training cohorts, internal validation cohorts, and external validation cohort, respectively. The calibration plots and DCA for predictions of OS were in excellent agreement. An online version of the nomogram was built for convenient clinical practice.ConclusionsOur nomogram can predict the OS of patients with T1-3N0M0 NSCLC after curative resection. The online version of our nomogram offer opportunities for fast personalized risk stratification and prognosis prediction in clinical practice.

Pretreatment and Posttreatment Tumor Metabolic Activity Assessed by FDG-PET/CT as Predictors of Tumor Recurrence and Survival Outcomes in Early-Stage Non-Small Cell Lung Cancer Treated With Stereotactic Body Radiation Therapy

Stereotactic body radiation therapy (SBRT) is considered the standard of care for medically inoperable early-stage non-small cell lung cancer. There is mixed evidence on the prognostic significance of tumor metabolic activity assessed by positron emission tomography combined with computed tomography (PET/CT) using F-18 fluorodeoxyglucose (FDG). The objectives of this study were to evaluate the maximum standardized uptake value (SUVmax) pretreatment and at 3 and 6 months after SBRT for prediction of tumor control and survival outcomes. Consecutive patients from a single institution with T12N0M0 non-small cell lung cancer receiving primary treatment with SBRT with pretreatment FDG-PET/CT (n=163) and follow-up FDG-PET/CT at 3 or 6 months (n=71) were included. Receiver operator characteristic analysis was performed to dichotomize variables for Kaplan-Meier survival analysis. Multivariate analysis was performed with Cox proportional hazards regression. Median follow-up was 19 months. For the whole cohort, 1-year and 2-year local control, progression-free survival (PFS), and overall survival (OS) were 95.0% and 80.3%, 87.1% and 75.4%, and 67.0% and 49.6% respectively. The following pre-SBRT SUVmax cutoffs were significant: SUV > 4.0 for distant failure-free survival (adjusted hazard ratio [aHR], 3.33, P=.006), >12.3 for PFS (aHR, 2.80, P=.011), and >12.6 for OS (aHR, 3.00, P=.003). SUVmax decreases of at least 45% at 3 months (aHR, 0.15, P=.018), and 53% at 6 months (aHR, 0.12, P=.046) were associated with improved local failure-free survival. Pre-SBRT SUVmax cutoffs can predict distant failure, PFS, and OS. At both 3 and 6 months after SBRT, cutoffs for percentage change in SUVmax can potentially stratify risk of local recurrence.

SWOG/NRG S1914: A Randomized Phase III Trial of Induction/Consolidation Atezolizumab + SBRT vs. SBRT Alone in High Risk, Early-Stage NSCLC (NCT#04214262)

<h3>Purpose/Objective(s)</h3> Stereotactic radiotherapy (SBRT) is the standard of care for early stage, medically inoperable non-small cell lung cancer (NSCLC). While rates of in-field control exceed 90% in prospective trials, rates of regional and distant control after SBRT remain suboptimal, and adjuvant chemotherapy is rarely used in this typically frail patient population. SWOG/NRG S1914 is a randomized phase III trial testing the addition of neoadjuvant, concurrent, and adjuvant atezolizumab to SBRT for early-stage NSCLC. <h3>Materials/Methods</h3> Eligible patients have T1-3N0M0 NSCLC ≤7cm and are medically inoperable or declined surgery. Patients must have at least one risk factor suggestive of increased risk of recurrence: tumor diameter ≥2 cm, SUV_max ≥6.2, or moderately/poorly/undifferentiated differentiated histology. Patients are randomized 1:1 to standard-of-care SBRT or to neoadjuvant, concurrent, and adjuvant atezolizumab 1200 mg IV Q3 week with SBRT initiated with cycle 3. Standard SBRT schedules of 3-5 fractions with a BED ≥100 are permitted. Stratification factors include location (central versus peripheral), size (<4 cm versus ≥4cm), and Zubrod performance status (0-1 vs 2). The primary objective of the study is to compare overall survival between the arms. The accrual goal is 480 patients to achieve 432 eligible patients based on a design with 80% power to rule out a null hazard ratio at the 1-sided 0.025 level, if the true hazard ratio were 0.70. The estimated duration of accrual and follow-up are 60 and 36 months, respectively and includes 4 interim analyses evaluating early stopping for futility or efficacy. Secondary objectives include comparisons of progression free survival (PFS), distant, locoregional and local failure rates, toxicity, and quality of life (EORTC QLQ-C30 and EORTC QLQ-LC13). <h3>Results</h3> Enrollment began 08/13/2020. As of 02/23/2022, 284 sites have been approved to enroll patients. 80 patients have enrolled and undergone randomization. <h3>Conclusion</h3> SWOG/NRG S1914 is a randomized phase III trial testing the addition of neoadjuvant, concurrent, and adjuvant atezolizumab to SABR in early-stage NSCLC.

Isolated Nodal Recurrence After Definitive Stereotactic Ablative Radiation Therapy for Non-Small Cell Lung Cancer

PurposeStereotactic ablative radiation therapy (SABR) results in high rates of primary tumor control for early-stage non-small cell lung cancer (NSCLC). For patients with isolated hilar or mediastinal nodal recurrence (INR) after SABR, the optimal salvage treatment strategy is unclear. The purpose of this study was to determine the rate of INR after SABR for early-stage NSCLC and to describe patterns of care and treatment outcomes after salvage therapy. Methods and MaterialsThis retrospective cohort study included 342 patients with stage T1-3N0M0 NSCLC treated with definitive SABR from 2003 to 2018. We evaluated the incidence of INR and baseline factors between patients who did and did not experience INR. Among patients who experienced INR, we described treatment patterns and outcomes including overall survival (OS) and progression free survival (PFS) from the time of nodal failure using the Kaplan-Meier method. ResultsWith a median follow-up of 3.3 years, the 3-year INR rate was 10.6% (95% CI, 6.6%-13.4%). Among the 34 patients experiencing INR, the 3-year rates of OS and PFS were 39.3% (24.4%-63.3%) and 26.7% (14.1%-0.3%), respectively. The 34 patients with INR were treated with radiation therapy alone (26.7%), concurrent chemoradiation therapy (43.3%), chemotherapy alone (13.3%), or observation (16.7%). Patients treated with concurrent chemoradiation therapy had the best survival outcomes, with a 3-year OS and PFS of 81.5% (61.1%-100.0%) and 63.9% (40.7%-100.0%), respectively. Of the patients treated with salvage radiation therapy or concurrent chemoradiation therapy, 14.3% experienced grade 3 toxic effects, and no patients had grade ≥4 toxic effects. ConclusionsIn this study, INR occurred in approximately 10% of patients treated with SABR for early-stage NSCLC. The highest rates of OS and PFS among patients with INR were observed in those treated with salvage chemoradiation therapy.

Who are the real high-risk patients with pathological T2N0M0 non-small-cell lung cancer that can benefit from adjuvant chemotherapy?

BackgroundThe benefit of adjuvant chemotherapy (ACT) in pathological T2N0M0 non-small-cell lung cancer (NSCLC) patients is not clear.MethodsOne thousand and fifty pathological T2N0M0 NSCLC patients were included and divided into two groups: with and without ACT. A propensity score matching analysis was carried out to minimize selection bias. The significance of ACT in high-risk patients was further analyzed. The Kaplan–Meier method and Cox proportional hazards model were used to assess the impact of ACT on the overall survival (OS), disease-free survival (DFS), and cancer-specific survival.ResultsFor the entire cohort, 31.9% (335/1050) of patients received ACT. After propensity score matching, 325 pairs of patients were matched. OS and DFS were comparable between groups in the original or matched cohort, which was confirmed by the multivariate analysis (all P > 0.05). In high-risk patients, the data suggest that ACT could improve OS and DFS only in patients with tumours >4 cm (OS: P = 0.003; DFS: P = 0.013). ACT could significantly improve the 5-year OS in patients with wild-type epidermal growth factor receptor (EGFR) (P = 0.022). ACT, however, could not improve cancer-specific survival in any subgroup, including patients with tumours >4 cm or wild-type EGFR (all P > 0.05). For patients with other high-risk factors, ACT failed to benefit patients in long-term outcomes.ConclusionsIn resected pT2N0M0 NSCLC patients, those with tumours >4 cm and wild-type EGFR are real high-risk patients and could gain survival benefit from ACT. Further prospective study is needed to confirm the definition.

Proton Beam Therapy in Elderly Patients With cT1-3N0M0 Non-small Cell Lung Cancer.

To investigate the outcomes of elderly patients with cT1-3N0M0 non-small cell lung cancer (NSCLC) undergoing proton beam therapy (PBT). Between 2009 and 2019, 110 patients receiving hypofractionated PBT for cT1-3N0M0 NSCLC were retrospectively reviewed. The median follow-up was 36.5 months (range=4.9-131.0 months). In the elderly group (80 years or older), the 3-year overall survival and progression-free survival rates were 79.8% and 73.9%, respectively, and the corresponding rates in the younger group were 80.5% and 61.2%, respectively. Grade 3 radiation pneumonitis (RP) was observed in 4.4% patients in the young group, whereas no grade 3 RP was observed in the elderly group. Age was not a risk factor for symptomatic RP. There were no significant differences in the survival and adverse events between the elderly and younger groups. PBT may be a reasonable approach for treating lung cancer in elderly patients with T1-3N0M0 NSCLC.

Wedge resection before lobectomy for patients with T1N0M0 non-small cell lung cancer: a propensity score matching analysis.

BackgroundWhether wedge resection of a tumor before lobectomy (Wed + Lob) can improve the prognosis of non-small cell lung cancer (NSCLC) has yet to be determined comprehensively. This study aimed to compare the effects of Wed + Lob with those of direct lobectomy (Lob) on survival and tumor cell dissemination in patients with T1N0M0 NSCLC.MethodsA cohort of 813 patients with T1N0M0 NSCLC who underwent lobectomy at a single center in China was investigated. After propensity score matching, the overall survival (OS) and disease-free survival (DFS) of patients were estimated using Kaplan-Meier plots. Associations between surgical strategies and patient survival were computed as hazard ratios and 95% confidence intervals using Cox proportional hazards regression models. Changes in folate receptor-positive circulating tumor cells (FR+ CTCs) after lobectomy were analyzed in another cohort from our hospital.ResultsA total of 401 Wed + Lob cases were matched with 255 Lob cases according to their propensity scores. Although no significant differences were found in OS, multivariate analysis showed that patients with T1N0M0 NSCLC in the Wed + Lob group had significantly improved DFS (HR =0.583; P=0.012) compared to those in the Lob group. After surgery, a decrease in FR+ CTCs was observed in 21 of 23 patients (91.3%) in the Wed + Lob group and in 16 of 23 patients (69.6%) in the Lob group [mean changes: 6.10 (±7.80) FU per 3 mL vs. 1.31 (±4.39) FU per 3 mL; P=0.014].ConclusionsWed + Lob may improve DFS and reduce tumor cell dissemination in patients with T1N0M0 NSCLC.

No Prognostic Impact of Staging Brain MRI in Patients with Stage IA Non-Small Cell Lung Cancer.

Background Although various guidelines discourage performing brain MRI for staging purposes in asymptomatic patients with clinical stage IA non-small cell lung cancer (NSCLC), evidence regarding their postoperative survival is lacking. Purpose To investigate the survival benefit of performing brain MRI in asymptomatic patients with early-stage NSCLC. Materials and Methods Patients who underwent curative resection between February 2009 and March 2016 for clinical TNM stage T1N0M0 NSCLC were retrospectively included. Patient survival and development of brain metastasis during postoperative surveillance were documented. The cumulative survival rate and incidence of brain metastasis were compared between patients who underwent surgery with or without staging brain MRI by using Cox regression and a Fine-Gray subdistribution hazard model, respectively, for multivariable adjustment. Propensity score matching and inverse probability of treatment weighting were applied for confounder adjustment. Results A total of 628 patients (mean age, 64 years ± 10 [SD]; 319 men) were included, of whom 53% (331 of 628) underwent staging brain MRI. In the multivariable analyses, brain MRI did not show prognostic benefits for brain metastasis-free survival (hazard ratio [HR], 1.06; 95% CI: 0.69, 1.63; P = .79), time to brain metastasis (HR, 1.60; 95% CI: 0.70, 3.94; P = .29), and overall survival (HR, 0.86; 95% CI, 0.54, 1.37; P = .54). Consistent results were obtained after propensity score matching (brain metastasis-free survival [HR, 0.97; 95% CI: 0.60, 1.57; P = .91], time to brain metastasis [HR, 1.29; 95% CI: 0.50, 3.33; P = .60], and overall survival [HR, 0.89; 95% CI: 0.53, 1.51; P = .67]) and inverse probability of treatment weighting. Conclusion No difference was observed between asymptomatic patients with clinical stage IA non-small cell lung cancer who underwent staging brain MRI and those who did not in terms of brain metastasis-free survival, time to brain metastasis, and overall survival. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Bizzi and Pascuzzo in this issue.

A Comparative Study of Patients With Early-Stage Non-Small Cell Lung Cancer Treated With Stereotactic Body Radiation Therapy Using CyberKnife and Linear Accelerator–Based Volumetric Modulated Arc Therapy

PurposeStereotactic body radiation therapy (SBRT) has become the standard of care for medically inoperable early-stage non-small cell lung cancer. We investigated 2 modalities of lung SBRT, CyberKnife (CK) and volumetric modulated arc therapy (VMAT), for differences in dosimetric parameters, tumor control, and clinical outcomes. Methods and MaterialsPatients who underwent SBRT for T1-2N0M0 non-small cell lung cancer from 2012 to 2018 were included. Dosimetric parameters for target volume coverage and organ-at-risk dose distribution were collected. Survival outcomes were evaluated using the Kaplan-Meier method with log-rank test. A multivariate Cox proportional hazards model was analyzed for local, regional, and distant tumor control; overall survival (OS) and progression-free survival; and radiation pneumonitis. ResultsTwo hundred twenty-seven patients (142 CK, 85 VMAT SBRT) met inclusion criteria. Overall, the local, regional, and distant control rates were 89.3%, 86.3%, and 87.4% at 2 years, and the OS was 67.5% and 32.8% at 2 and 5 years, respectively. VMAT delivered higher maximum doses to the gross tumor volume and planning target volume and had a lower lung and heart V5. Although there was no difference in local or distant failure, progression-free survival, or OS, VMAT was associated with superior freedom from regional failure (adjusted hazard ratio, 0.26; P = .045). With no difference between treatment modalities, 11.9% of patients developed grade 1 to 2 radiation pneumonitis. There were no grade 3+ events of radiation pneumonitis. ConclusionsThis study revealed that VMAT and CK provided comparable local and distant control and survival outcomes; however, VMAT exhibited better regional control. Further study in this regard is imperative.

Role of stereotactic body radiotherapy for early-stage non-small-cell lung cancer in patients borderline for surgery due to impaired pulmonary function.

Stereotactic body radiotherapy (SBRT) is recommended only for inoperable patients with early-stage (e-stage) non-small-cell lung cancer (NSCLC). We compared outcomes between surgery and SBRT in patients borderline for surgery due to impaired pulmonary function (PF). We reviewed single-institution retrospective data of 578 patients with clinically T1-2N0M0 NSCLC treated by surgery or SBRT between 2004 and 2014, and extracted a cohort with borderline impaired PF for surgery, which was defined as predicted postoperative (PPO) forced expiratory volume in 1 s (FEV1 ) of<50% and ≥30%. Overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) were compared between surgery and SBRT using propensity score-matching (PSM) to avoid bias. Among a total of 116 eligible patients with a median PPO FEV1 of 45%, PSM identified 25 patients from each group with similar characteristics. The median age, pretreatment FEV1 , and follow-up durations for the surgery and SBRT groups were 75 and 74 years, 58% and 56%, and 56 and 60 months, respectively. The 5-year OS, CSS, and DFS rates of the surgery versus SBRT groups were 60%versus 63%, 76%versus 81%, and 52%versus 48%, respectively (p=0.97, 0.81, and 0.99). The surgical mortality was 4.0%, but no treatment-related death was observed after SBRT. The incidence of ≥ grade 2 adverse events after surgery was double that after SBRT (40%versus 20%, p=.22). Our study suggests that SBRT is a reasonable option for patients with e-stage NSCLC and impaired PF who are considered borderline candidates for surgery.

A standard for hilar and intrapulmonary lymph node dissection and pathological examination in early non-small cell lung cancer.

BackgroundThere is considerable variation in the staging of lymph nodes (LNs) as part of tumor, node, metastasis (TNM) staging of non-small cell lung cancer (NSCLC). A new dissection and pathological examination standard for hilar and intrapulmonary LNs needs to be established for patients with early-stage T1–3N0M0 NSCLC.MethodsThis study involved 3,002 patients with T1–3N0M0 NSCLC who underwent radical lobectomy or total pneumonectomy in the thoracic departments of 11 Chinese institutions between January 1999 and October 2013. The Cox model was applied for univariate and multivariate analyses in the examination of station 10, 11 LN and station 12, 13, 14 LN. A hilar and intrapulmonary standard (HI standard) was then established based on univariate and multiple-factor analyses conducted using the Cox model.ResultsAmong the 3,002 patients enrolled in the study, 2,609 underwent at least one examination of station 10, 11 LN (A1), while 393 did not undergo examination of station 10, 11 LN (A0). The A0 and A1 groups had 5-year survival rates of 76% and 80%, respectively (P=0.018). Further, 1,764 patients underwent at least one examination of station 12, 13, 14 LN (B1), while 1,238 patients did not (B0). The B0 and B1 groups had 5-year survival rates of 77% and 82%, respectively (P=0.008). In total, 1,269 patients attained the HI standard (C1), and 1,733 did not (C0). The C0 and C1 groups had 5-year survival rates of 77% and 83%, respectively (P<0.001).ConclusionsThe HI standard can improve both the prognosis and survival rates of patients with T1–3N0M0 NSCLC. This will provide important guidance for pulmonary LN dissection and pathological examination in NSCLC cases.

Lobectomy versus segmentectomy: a propensity score-matched comparison of postoperative complications, pulmonary function and prognosis.

OBJECTIVESTo demonstrate the differences in clinical outcomes between lobectomy and segmentectomy for non-small cell lung cancer using propensity score matching.METHODSA single-centre, retrospective, matched cohort study was conducted in clinical T1N0M0 non-small cell lung cancer patients treated by surgery between 2012 and 2019. Differences in freedom from recurrence, overall survival, postoperative complications, chest drainage and preservation of pulmonary function between lobectomy and segmentectomy were evaluated using the propensity score model. Matched variables of patients were age, sex, comorbidity index and pulmonary function. Matched variables of tumours were tumour size, T-stage, fluorodeoxyglucose uptake on positron emission tomography, histopathology, lobe site and tumour distance ratio from the hilum.RESULTSOf the 112 patients treated by lobectomy and 233 patients treated by segmentectomy, 93 patients each from both groups were selected after the matching. The median tumour distance ratio from hilum was 0.7 in lobectomy and 0.8 in segmentectomy group (P = 0.59), i.e. almost outer third tumour location. There were no significant differences in freedom from recurrence (P = 0.38), overall survival (P = 0.51), postoperative complications (P = 0.94), drainage period (P = 0.53) and prolonged air leakage (P = 0.82) between the two. Median preservation of pulmonary function was 93.2% after segmentectomy, which was significantly higher than 85.9% after lobectomy (P < 0.001).CONCLUSIONSFreedom from recurrence, overall survival, postoperative complications and chest drainage were similar between segmentectomy and lobectomy. Segmentectomy could be one of the options for clinical T1N0M0 non-small cell lung cancer located outer third as well as being able to preserve pulmonary function better than lobectomy.Clinical trial registrationName: Retrospective analysis of segmentectomy and lobectomy for cT1N0M0 non-small cell lung cancerDate of approval: February 2014Number of IRB approval: 14-003.

Tumor Control and Survival Outcomes Based on Maximum Standardized Uptake Value on FDG-PET/CT in T1-2 NSCLC Treated With SBRT

<h3>Purpose/Objective(s)</h3> Stereotactic body radiotherapy (SBRT) is standard of care in medically inoperable early-stage non-small cell lung cancer (NSCLC). Assessment of maximum standardized uptake value (SUVmax) on FDG-PET/CT before and after SBRT may stratify tumor control and survival outcomes. <h3>Materials/Methods</h3> Retrospective chart review identified patients with T1-2N0M0 NSCLC who were only treated with SBRT between 2012 and 2019. Pretreatment SUVmax and percent change in SUVmax at 3 and 6 months following SBRT were assessed as independent predictors of local control (LC), regional failure-free survival (RFFS), distant failure-free survival (DFFS), progression-free survival (PFS), and overall survival (OS). Receiver operator characteristic (ROC) analysis yielded optimal cut points for comparison. Survival analyses were performed with Kaplan-Meier estimates with log rank testing, and Cox proportional hazards models including age, sex, T stage, histology, and performance status. <h3>Results</h3> 71 (43.6%) out of 163 patients underwent repeat PET/CT within 6 months of SBRT completion. Median follow-up was 19 months (range 1 – 94 months). For the whole cohort, 1-year and 2-year LC, PFS, and OS were 95.0% and 80.3%, 75.9% and 47.7%, and 87.1% and 67.0%, respectively. For DFFS, pretreatment SUVmax greater than 4 had an aHR of 3.33 (95% CI 1.42 – 7.84, <i>P</i> = 0.006). Pre-SBRT SUVmax over 12.3 had an aHR of 2.80 (95% CI 1.3 – 6.2, <i>P</i> = 0.011) for PFS, and a cut point of 12.6 had an aHR of 3.00 (95% CI 1.6 – 5.8, <i>P</i> = 0.003) for OS. Pretreatment SUVmax did not significantly predict LC or RFFS. At 3 months following SBRT, an SUVmax decrease of at least 45% was associated with improved LC (aHR = 0.15, 95% CI 0.02 – 0.91, <i>P</i> = 0.018). A 6-month SUVmax decrease of more than 53% was associated with better LC (<i>P</i> = 0.038), and a decrease over 11% was associated with improved RFFS (aHR = 0.12, 95% CI 0.02 – 0.96, <i>P</i> = 0.046). Change in SUVmax was not significantly associated with DFFS, PFS, or OS at either time point. No factors other than performance status for PFS and OS were significant. <h3>Conclusion</h3> At 3 and 6 months following SBRT, cut points for percentage change in SUVmax can stratify risk of local recurrence and possibly regional recurrence. Pretreatment SUVmax cutoffs can predict distant failure, progression-free survival, and overall survival in early-stage NSCLC.

Role of Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer in Borderline Patients for Surgery due to Impaired Pulmonary Function

Stereotactic body radiotherapy (SBRT) is recommended only for inoperable patients with early stage (e-stage) non-small cell lung cancer (NSCLC). We compared outcomes between surgery and SBRT in borderline patients for surgery due to impaired pulmonary function (PF).In our institution, operable patients (i.e., sufficient PF and no serious comorbidity) were generally selected for surgery after discussion among the multidisciplinary team. The inoperable patients decided after discussion among the multidisciplinary team and those who refused surgery were usually selected for SBRT. The total dose of 44 or 48 Gy for tumors with a maximum diameter < 1.5 cm, 48 or 50 Gy for tumors of 1.5-3 cm, and 52 Gy for tumors > 3 cm was prescribed to the isocenter of the planning target volume. Surgery included lobectomy, sub lobar resection (SLR), and wedge resection (WR) by video-assisted thoracic surgery or open thoracotomy at the thoracic surgeons' discretion. We reviewed single-institutional retrospective data of 578 patients with clinically T1-2N0M0 NSCLC treated by surgery or SBRT between 2004 and 2014, and extracted a cohort with borderline impaired PF for surgery, which was defined as predicted postoperative (PPO) forced expiratory volume in 1 second (FEV1) of < 50% and ≥ 30%. Overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) were compared between surgery and SBRT using propensity score-matching (PSM) to avoid bias.Among a total of 116 eligible patients with a median PPO FEV1 of 45%, PSM identified 25 patients from each group with similar characteristics. After PSM, 17 (68%), 3 (12%), and 5 (20%) patients underwent lobectomy, SLR, and WR, respectively. The median age, pretreatment FEV1, and follow-up durations for the surgery and SBRT groups were 75 and 74 years, 58% and 56%, and 56 and 60 months, respectively. The 5-year OS, CSS, and DFS rates of the surgery vs SBRT groups were 60% vs 63%, 76% vs 81%, and 52% vs 48%, respectively (P = 0.97, 0.81, and 0.99). Among the matched patients, one patient died of massive hemorrhage during lobectomy. The 90-day surgical mortality was 4.0% (1 of 25), but no treatment-related death was observed after SBRT. In the surgery group after PSM, 10 (40%) patients had grade 2 or greater adverse events. In the SBRT group after PSM, 5 (20%) patients had treatment-related grade 2 or greater adverse events. After PSM, the incidence of grade 2 or greater adverse events in the surgery group was twice as high as that in the SBRT group, but this difference was not significant by the χ2 test (40% vs 20%, P = 0.22).Although surgery and SBRT had similar survivals, fewer adverse events were observed after SBRT. Our current study suggests that SBRT is a reasonable option for impaired PF patients borderline for surgery in e-stage NSCLC. However, a prospective study of this specific population is warranted in order to improve patient selection for SBRT or surgery.

Risk stratification and adjuvant chemotherapy after radical resection based on the clinical risk scores of patients with stage IB-IIA non-small cell lung cancer

IntroductionDespite the heterogeneity among patients with stage IB-IIA non-small cell lung cancer (NSCLC), clinically applicable models to identify patients most suitable for receiving adjuvant chemotherapy (ACT) are limited. We aimed to develop a model for risk stratification and the individualized application of ACT. MethodsBetween January 2008 and March 2018, patients with T2N0M0 NSCLC at Sun Yat-sen University Cancer Center were retrospectively enrolled. Survival curves were estimated by Kaplan-Meier method and compared with log-rank test. Cox regression models were used to identify prognostic factors for disease-free survival (DFS) and overall survival (OS). Propensity score matching (PSM) was implemented. Subgroup analysis was performed based on clinical risk score (CRS) value and epidermal growth factor receptor (EGFR) mutation status. ResultsOf 1063 patients with T2N0 NSCLC enrolled, 272 patients received ACT. Before PSM, patients with high CRS (>1) had a significantly worse OS and DFS outcomes. In the PSM, the baseline characteristics of the 270 pairs of patients were well matched. ACT was associated with improved OS outcomes for patients with a high CRS, while ACT was associated with improved OS and DFS outcomes in patients with wild-type EGFR. The interaction analysis showed an apparent interaction effect between ACT and EGFR-activating mutations as well as chemotherapy regimens and histology. ConclusionsThe CRS can predict the prognosis of patients with stage IB-IIA NSCLC. ACT could improve the outcome of patients with a high CRS. Patients with non-squamous cell histology receiving pemetrexed plus platinum might benefit more, but not those with EGFR-activating mutations.