Clinical Stage IIIA Non-small Cell Lung Cancer Research Articles

Sociodemographic factors affecting survival in stage IIIA NSCLC treated with surgery-based treatment or definitive chemoradiation with immunotherapy consolidation: An NCDB analysis.

e18555 Background: Stage IIIA non-small cell lung cancer (NSCLC) is a heterogeneous disease treated by surgery-based approach or definitive chemoradiation (CRT) and immunotherapy (ICI) consolidation. Studies have shown that black patients in general are diagnosed at advanced stages, are less likely to receive ICI, and have lower overall survival (OS) compared to whites. Importantly, ICI was shown to impart similar or even better OS among advanced-stage black NSCLC patients, compared to whites. Geographical location and socioeconomic status have also been shown to affect outcomes. There are no studies on sociodemographic factors affecting survival in stage IIIA NSCLC in the ICI era. Methods: We used National Cancer Database (NCDB) to identify 23,110 patients with clinical stage IIIA NSCLC treated with either surgery-based approach or definitive CRT followed by ICI during 2017-2019, and surgery-based treatment or CRT during 2014-2016. We analyzed age, race, sex, insurance type, income, geographic location, Charlson Comorbidity Index (CCI) and education. Kaplan-Meier (KM) plots were used to examine survival curves and descriptive analysis was performed to examine the characteristics of sociodemographic variables by the two treatment modalities. Cox regression analysis was used to identify factors associated with OS. Results: ICI maintenance improved the OS of all stage IIIA NSCLC patients after CRT during 2017-2019 compared to CRT only in 2014-2016. On multivariate analysis of surgical and CRT-ICI cohorts, blacks had slightly better OS compared to whites (HR, 95%CI, p-value) (0.89, 0.84-0.95, < 0.001) but lower than other races including Asians (0.77, 0.69-0.87, < 0.001). While there was no OS difference in the surgical arm (0.94, 0.83-1.07, p = 0.356) between black and white patients, better survival was seen in blacks in the CRT-ICI arm (0.88, 0.82-0.94, < 0.001). No significant interaction between race and CRT-ICI was identified which indicates the benefit of CRT-ICI is independent of the race effect. Other factors associated with lower OS were older age with age > 75 HR 1.00, ages 19-39 (0.47, 0.35-0.64) ages 40-64 (0.71, 0.67-0.75), ages 65-74 (0.79, 0.76-0.83), median quartile income < $40,227 (1.07, 1.01-1.14), non-metro location (1.12, 1.07-1.17), non-academic facility (1.09, 1.05-1.14), and male sex (1.24, 1.20-1.29). Insurance status had no effect on OS. Conclusions: Our study indicates that there is no survival difference between white and black patients treated with surgery, but blacks had better survival when treated with CRT-ICI. Racial disparity in NSCLC survival depends on stage and access to care. Treatment modality, income, metro location, and access to an academic center are more significant predictors of survival than race. Interestingly, health insurance had no impact on OS.

Efficacy of radiomics model based on the concept of gross tumor volume and clinical target volume in predicting occult lymph node metastasis in non-small cell lung cancer.

This study aimed to establish a predictive model for occult lymph node metastasis (LNM) in patients with clinical stage I-A non-small cell lung cancer (NSCLC) based on contrast-enhanced CT. A total of 598 patients with stage I-IIA NSCLC from different hospitals were randomized into the training and validation group. The "Radiomics" tool kit of AccuContour software was employed to extract the radiomics features of GTV and CTV from chest-enhanced CT arterial phase pictures. Then, the least absolute shrinkage and selection operator (LASSO) regression analysis was applied to reduce the number of variables and develop GTV, CTV, and GTV+CTV models for predicting occult lymph node metastasis (LNM). Eight optimal radiomics features related to occult LNM were finally identified. The receiver operating characteristic (ROC) curves of the three models showed good predictive effects. The area under the curve (AUC) value of GTV, CTV, and GTV+CTV model in the training group was 0.845, 0.843, and 0.869, respectively. Similarly, the corresponding AUC values in the validation group were 0.821, 0.812, and 0.906. The combined GTV+CTV model exhibited a better predictive performance in the training and validation group by the Delong test (p<0.05). Moreover, the decision curve showed that the combined GTV+CTV predictive model was superior to the GTV or CTV model. The radiomics prediction models based on GTV and CTV can predict occult LNM in patients with clinical stage I-IIA NSCLC preoperatively, and the combined GTV+CTV model is the optimal strategy for clinical application.

949TiP Neoadjuvant durvalumab in non-surgical early stage/locally advanced non-small cell lung cancer (NSCLC) followed by radical RT/CRT (IDEAR) study concept of a phase II investigator initiated clinical trial

Targeting the PD1/PD-L1 pathway has demonstrated activity in patients with advanced malignancies. Treatment with anti-PD1/PD-L1 blockade in advanced and locally advanced NSCLC, is already standard of care. The positive outcomes of durvalumab following CRT emphasized the potential of immunotherapy integration in multimodality treatment strategies and in earlier phases of the disease, leading to the first immune checkpoint inhibitor approval in non-metastatic setting in NSCLC. This study proposes to evaluate the safety and efficacy of an anti-PD-L1 (durvalumab) agent as neoadjuvant therapy in patients with localized NSCLC who are planned to undergo radical RT or CRT. Main inclusion criteria: ≥ 18 y/o; histologically documented NSCLC; clinical Stage IIIA NSCLC eligible for RT or clinical stage IB (≥ 4 cm)-IIIA NSCLC that are not considered for surgical treatment by the clinical team or by patient choice who, however, are eligible for radical RT or CRT; ≥ 1 measurable lesion by RECIST v1.1. This is a Phase Ib/II, single-center, open-label, single-arm study, expected to expand to other center within the country. Durvalumab will be administered as neoadjuvant therapy before standard of care RT/CRT to 30 patients with untreated NSCLC not amenable for surgery but planned to undergo radical RT or CRT. The primary endpoint is the rate of patients without Dose-Limiting Toxicity (DLT). The study will be conducted in two parts; the first, DLT will be evaluated on a total of 18 patients over 3 cohorts; the second, an expansion cohort of 12 patients will be enrolled to further evaluate the safety, efficacy and feasibility of neoadjuvant durvalumab followed by standard of care RT/CRT. A single IV infusion of durvalumab 1500 mg will be administered at Visit 1. RT/RCT will be initiated between 4-5 weeks after. Standard RT/CRT and adjuvant treatment will be offered according to clinical practice. After completion of RT/RCT patients will be treated according to standard of care. A biomarker sub-study will be performed. Tumor and immune cells phenotype, somatic genetic alterations evaluation of tumor sample and ctDNA will be assessed. NCT05267392. IPO-Porto and AstraZeneca.

Use of Surgery and Stereotactic Body Radiotherapy (SBRT) In Very Elderly Patients with Early Stage Non-Small Cell Lung Cancer (NSCLC): A National Cancer Database (NCDB) Analysis

SBRT treatment for very elderly (>80 years) patients with early stage NSCLC has been reported to be well tolerated with good short-term efficacy. Using a large hospital-based registry, we report a comparison of patterns of practice, outcomes, and prognostic factors for very elderly patients undergoing any treatment for early-stage NSCLC. The NCDB was queried for patients with clinical Stage I-IIA NSCLC with age ≥ 80 years diagnosed from 2004-2015 treated with surgery or SBRT alone. Patients were excluded if they received chemotherapy /immunotherapy or non-standard SBRT doses (i.e., > 5 fractions of RT, <30 Gy or >70 Gy total dose). Survival analyses were performed with propensity-matching, Kaplan-Meier estimates, Cox proportional hazards regression, and log-rank testing. 26039 patients met search criteria, median age 83 (80-90) years. 17141 (65.8%) patients underwent surgery, and 8898 (34.2%) underwent SBRT. Median follow up was 31 months. Median survival was 52 months for surgery and 35 months for SBRT. Of patients receiving SBRT, 2044 (23%) had a contraindication to primary surgery due to patient risk factors. 83% of patients were treated at comprehensive or academic/research cancer facilities. Age, clinical stage, tumor size, surgery type, CDCC score, BED, bronchial involvement, and type of treatment facility were predictive of median survival. BED > 154 Gy was associated with greater median survival (p<0.01). Lobectomy was associated with greater median survival vs sub-lobar resection or pneumonectomy (p<0.0001). Treatment at a community cancer program was associated with lower median survival. For Stage I tumors, surgery was associated with better median survival (56 months vs. 35 months, p < 0.0001), but for Stage IIA patients, both modalities had similar median survival (30 months vs 29 months, p = 0.04). Surgery remains the predominant treatment modality for early stage NSCLC in this very elderly patient population, and is associated with good outcomes for patients with Stage I tumors. For elderly patients who are poor surgical candidates due to medical co-morbidities SBRT is associated with reasonable median survival.

Use of surgery and stereotactic body radiotherapy (SBRT) in very elderly patients with early-stage non-small cell lung cancer (NSCLC): A national cancer database (NCDB) analysis.

e20058 Background: SBRT treatment for very elderly ( &gt; 80 years) patients with early stage NSCLC has been reported to be well tolerated with good short term efficacy. Using a large hospital based registry, we report a comparison of patterns of practice, outcomes, and prognostic factors for very elderly patients undergoing any treatment for early-stage NSCLC. Methods: The NCDB was queried for patients with clinical Stage I-IIA NSCLC with age ≥ 80 years diagnosed from 2001-2015 treated with surgery or SBRT alone. Patients were excluded if they received chemotherapy /immunotherapy or non-standard SBRT doses (i.e. &gt; 5 fractions of RT, &lt; 30 Gy or &gt; 70 Gy total dose). Survival analyses were performed with propensity-matching, Kaplan-Meier estimates, Cox proportional hazards regression, and log rank testing. Results: 26039 patients met search criteria, median age 83 (80-90) years. 17141 (65.8%) patients underwent surgery, and 8898 (34.2%) underwent SBRT. Median follow up was 31 months. Median survival was 52 and 35 months for surgery and SBRT. Of patients receiving SBRT, 2044 (23%) had a contraindication to primary surgery due to patient risk factors. Age, clinical stage, tumor size, surgery type, CDCC score, BED, bronchial involvement, and type of treatment facility were predictive of median survival. BED &gt; 154 Gy was associated with greater median survival (p &lt; 0.01). Lobectomy was associated with greater median survival vs sub-lobar resection/pneumonectomy (p &lt; 0.0001). For stage I tumors, surgery was associated with better median survival (56 vs. 35 months, p &lt; 0.0001), but for stage IIA patients both modalities had similar median survival (30 vs 29 months, p = 0.04). Conclusions: Surgery remains the predominant treatment modality for early stage NSCLC in this very elderly population, and is associated with good outcomes for patients with stage I tumors. For elderly patients who are poor surgical candidates due to medical co-morbidities SBRT is associated with reasonable median survival. With limited information on patient comorbidities, more robust studies are needed to determine the effects of patient selection on treatment outcomes in this population.

Pneumonectomy for Clinical Stage IIIA Non-Small Cell Lung Cancer: The Effect of Neoadjuvant Therapy

The role of pneumonectomy after neoadjuvant therapy for stage IIIA non-small cell lung cancer (NSCLC) remains uncertain. Patients who underwent pneumonectomy for clinical stage IIIA NSCLC were abstracted from the National Cancer Database. Individuals treated with neoadjuvant therapy, followed by resection, were compared with those who underwent resection, followed by adjuvant therapy. Logistic regression was performed to identify factors associated with 30-day mortality. A Cox proportional hazards model was fitted to identify factors associated with survival. Pneumonectomy for stage IIIA NSCLC with R0 resection was performed in 1,033 patients; of these, 739 (71%) received neoadjuvant therapy, and 294 (29%) underwent resection, followed by adjuvant therapy. The two groups were well matched for age, gender, race, income, Charlson comorbidity score, and tumor size. The 30-day mortality rate in the neoadjuvant group was 7.8% (57 of 739). Median survival was similar between the two groups: 25.9 months neoadjuvant vs 31.3 months adjuvant (p= 0.74). A multivariable logistic regression model for 30-day mortality demonstrated that increasing age, annual income of less than $35,000, nonacademic facility, and right-sided resection were associated withan elevated risk of 30-day mortality. A multivariable Cox model for survival demonstrated that increasing age was predictive of shorter survival and that administration of neoadjuvant therapy did not confer asurvival advantage over adjuvant therapy (p=0.59). Most patients who require pneumonectomy for clinical stage IIIA NSCLC receive neoadjuvant chemoradiotherapy, without an improvement in survival. In these patients, primary resection, followed by adjuvant chemoradiotherapy, may provide equivalent long-term outcomes.

The Role of Surgical Resection in Stage IIIA Non-Small Cell Lung Cancer: A Decision and Cost-Effectiveness Analysis

This study evaluated the cost-effectiveness of combination chemotherapy, radiotherapy, and surgical intervention (CRS) vs definitive chemotherapy and radiotherapy (CR) in clinical stage IIIA non-small cell lung cancer (NSCLC) patients at academic and nonacademic centers. Patients with clinical stage IIIA NSCLC receiving CR or CRS from 1998 to 2010 were identified in the National Cancer Data Base. Propensity score matching on patient, tumor, and treatment characteristics was performed. Medicare allowable charges were used for treatment costs. The incremental cost-effectiveness ratio (ICER) was based on probabilistic 5-year survival and calculated as cost per life-year gained. We identified 5,265 CR and CRS matched patient pairs. Surgical resection imparted an increased effectiveness of 0.83 life-years, with an ICER of $17,618. Among nonacademic centers, 1,634 matched CR and CRS patients demonstrated a benefit with surgical resection of 0.86 life-years gained, for an ICER of $17,124. At academic centers, 3,201 matched CR and CRS patients had increased survival of 0.81 life-years with surgical resection, for an ICER of $18,144. Finally, 3,713 CRS patients were matched between academic and nonacademic centers. Academic center surgical patients had an increased effectiveness of 1.5 months gained and dominated the model with lower surgical cost estimates associated with lower 30-day mortality rates. In stage IIIA NSCLC, the selective addition of surgical resection to CR is cost-effective compared with definitive chemoradiation therapy at nonacademic and academic centers. These conclusions are valid over a range of clinically meaningful variations in cost and treatment outcomes.

Multidisciplinary Treatment for Stage IIIA Non-Small Cell Lung Cancer: Does Institution Type Matter?

Improved survival of patients with early-stage non-small cell lung cancer (NSCLC) undergoing resection at high-volume centers has been reported. However, the effect of institution is unclear in stage IIIA NSCLC, where a variety of neoadjuvant and adjuvant therapies are used. Treatment and outcomes data of clinical stage IIIA NSCLC patients undergoing resection as part of multimodality therapy was obtained from the National Cancer Database. Multivariable regression models were fitted to evaluate variables influencing 30-day mortality and overall survival. From 1998 to 2010, 11,492 clinical stage IIIA patients underwent resection at community centers, and 7,743 patients received resection at academic centers. Academic center patients were more likely to be younger, female, non-Caucasian, have a lower Charlson-Deyo comorbidity score, and to receive neoadjuvant chemotherapy (49.6% vs 40.6%; all p < 0.001). Higher 30-day mortality was associated with increasing age, male gender, preoperative radiotherapy, and pneumonectomy. Patients undergoing operations at academic centers experienced lower 30-day mortality (3.3% vs 4.5%; odds ratio, 0.75; 95% confidence interval [CI], 0.60 to 0.93; p < 0.001). Decreased long-term survival was associated with increasing age, male gender, higher Charlson-Deyo comorbidity score, and larger tumors. Neoadjuvant chemotherapy (hazard ratio, 0.66; 95% CI, 0.62 to 0.70), surgical intervention at an academic center (hazard ratio, 0.92; 95% CI, 0.88 to 0.97), and lobectomy (hazard ratio, 0.72; 95% CI, 0.67 to 0.77) were associated with improved overall survival. Stage IIIA NSCLC patients undergoing resection at academic centers had lower 30-day mortality and increased overall survival compared with patients treated at community centers, possibly due to higher patient volume and an increased rate of neoadjuvant chemotherapy.

Trimodality therapy in the treatment of stage IIIA non-small cell lung cancer (NSCLC): Analysis of the National Cancer Database.

7514 Background: Significant controversy remains regarding the care of patients (pts) with clinical stage IIIA NSCLC. While multi-modality therapy is an acceptable strategy in selected pts, the opt...

Current status of induction treatment for N2-Stage III non-small cell lung cancer.

Locally advanced non-small cell lung cancer (NSCLC), particularly clinical Stage IIIA NSCLC with mediastinal lymph node metastasis, is known to be quite heterogeneous, comprising approximately one-fourth of cases of NSCLC. In this subset, patients with a minor tumor load in the mediastinal lymph nodes, such as microscopically or pathologically proven N2 in the resected specimens, are treated with surgery followed by adjuvant chemotherapy. Meanwhile, the current standard of care for patients with bulky or infiltrative N2 disease is concurrent chemoradiotherapy. The potential role of surgery in multi-modality treatment for clinical N2-Stage IIIA remains controversial. Several prospective clinical trials of this subset have been conducted; however, the heterogeneity of the N2 status and differences in chemotherapy regimens and/or radiation modalities between clinical trials make the results difficult to compare. No optimal chemotherapy regimen has been established to control possible micrometastasis, and radiotherapy is often used to achieve maximum local disease control and minimize post-surgical complications. This review summarizes the findings of prospective clinical trials that assessed the role of surgery in treating clinical N2-Stage IIIA patients within the last two decades and discusses the present status of induction treatment followed by surgery for clinical N2-Stage IIIA NSCLC.

National Patterns of Care and Outcomes After Combined Modality Therapy for Stage IIIA Non–Small-Cell Lung Cancer

The role of surgery in addition to chemotherapy and radiation for stage IIIA non-small-cell lung cancer (NSCLC) remains controversial. Because there are limited data on the benefit from surgery in this setting, we evaluated the use of combined modality therapy nationally and explored the outcomes with and without the addition of surgery. Patient variables and treatment-related outcomes were abstracted for patients with clinical stage IIIA NSCLC from the National Cancer Database. Patients receiving chemotherapy and radiation were compared with those undergoing chemotherapy, radiation, and surgery (CRS) in any sequence. Between 1998 and 2010, 61,339 patients underwent combined modality treatment for clinical stage IIIA NSCLC. Of these, 51,979 (84.7%) received chemotherapy and radiation while 9360 (15.3%) underwent CRS. Patients in the CRS group were younger, more likely female patients and Caucasians, and had smaller tumors and lower Charlson comorbidity scores. The 30-day surgical mortality was 200 of 8993 (2.2%). The median overall survival favored the CRS group in both unmatched (32.4 months versus 15.7 months, p < 0.001) and matched analysis based on patient characteristics (34.3 versus 18.4 months, p < 0.001). There is significant heterogeneity in the treatment of stage IIIA NSCLC in the United States. Patients selected for surgery in addition to chemoradiation therapy seem to have better long-term survival.

Induction chemotherapy with gemcitabine-carboplatin-paclitaxel (GEMCAP) in stage III non-small cell lung cancer (NSCLC).

7063 Background: The addition of gemcitabine (G) to doublet chemotherapy with carboplatin (C) and paclitaxel (P) has demonstrated to improve clinical outcome of advanced stage IIIB and IV NSCLC in a phase II-III study, albeit with significant hematologic toxicity. In a previous dose finding study, we identified a safe GEMCAP regimen based on dose-limiting toxicities. Methods: Patients aged 18-75 years, with ECOG PS 0-1, and unresectable clinical stage IIIA NSCLC, or stage IIIB suitable for definitive radiation treatment were treated in a phase II study with C AUC 5 i.v., P 175 mg/m2 i.v. on day 1, and G 800 mg/m2 i.v. on days 1 and 8, every 3 weeks for 3 cycles. Patients with stage IIIA disease in response following GEMCAP were reassessed for surgery; those with unresectable stage IIIA disease and stage IIIB, were treated with radiotherapy. Primary endpoint was response rate. Secondary endpoints included: toxicity, progression-free survival (PFS), resection rate, and overall survival (OS). Results: Of the 53 enrolled patients, 42 were males, 11 females, 29 (55%) had stage IIIA, 24 (45%) stage IIIB NSCLC, 47 (89%) had a PS 0. Forty partial responses and one complete response were observed, for an overall response rate of 80%. G3-4 and G2 toxicities, occurring in ≥ 5% of patients, included: neutropenia (19-8%), hypertransaminemia (11-2%), diarrhoea (6-0%), G3-4 toxicities; neutropenia (34%), asthenia (25%), diarrhoea (15%), peripheral neuropathy (13%), osteomialgya (11%), hypertransaminemia (6%), nausea/vomiting (9%), G2 toxicity. With a median follow-up of 20 months (range, 6-77) PFS was 10.5 months (95% CI, 9.9-11.4); OS was 21.1 months (95% CI, 19.6-22.9). Thirteen patients were operated, for a resection rate of 44%. Conclusions: The GEMCAP regimen at the dose employed produced high response and resection rate, with acceptable toxicity, as induction chemotherapy for clinical stage III NSCLC. PFS and OS compared favourably with that expected for clinical stage III disease.

Equivalent outcome of patients with clinical Stage IIIA non–small-cell lung cancer treated with concurrent chemoradiation compared with induction chemotherapy followed by surgical resection

Purpose To compare the outcome of induction chemotherapy followed by surgery (C/S) and concurrent chemoradiotherapy (CRT) for clinical Stage IIIA non–small-cell lung cancer (NSCLC). Methods and materials Between 1990 and 2000, 107 patients underwent either induction C/S ( n = 55) or concurrent CRT ( n = 52) for clinical Stage IIIA NSCLC at The University of Texas M. D. Anderson Cancer Center. Patient and tumor characteristics were balanced in the two treatment groups with respect to T and N stage, race, median age, performance status, weight loss, and histologic findings. In the C/S group, induction chemotherapy included two to four cycles of cisplatin-based chemotherapy followed by lobectomy and mediastinal lymph node dissection. Postoperative RT was delivered in 35 patients, with referral for RT made at the discretion of the treating physician. CRT consisted of three cycles of cisplatin-based chemotherapy given every 3 weeks concurrent with RT to 60–63 Gy in 30–35 fractions in 27 patients and 69.6 Gy in 58 fractions (b.i.d.) in 25 patients. Local control, overall disease-free survival, and distant metastasis-free survival rates were calculated using the Kaplan-Meier method. The median follow-up duration was 20 months in all patients and 32 months in surviving patients. Results No statistically significant differences were found in the end points measured in the two treatment groups. Specifically, the median survival time was 31 and 27 months and the 5-year overall survival rate was 33% and 30% in the C/S and CRT groups, respectively. Likewise, the 5-year local control (58% vs. 61%), disease-free (24% vs. 23%), and distant metastasis-free (44% vs. 36%) survival rates in the two groups were not significantly different. In the C/S group, postoperative RT significantly improved the 5-year local control rate from 33.8% to 81.5% ( p = 0.007) but did not significantly improve overall survival. Additionally, patients in the C/S group whose disease responded to induction chemotherapy had a significantly improved 5-year overall survival rate (50%) compared with those who had stable or progressive disease (16%, p = 0001). Conclusion Treatment of Stage IIIA NSCLC using either induction C/S or CRT resulted in similar outcomes in terms of local control and median overall, 5-year overall, distant metastasis-free, and disease-free survival. However, patients undergoing induction C/S often needed postoperative RT to achieve local control equivalent to that achieved with concurrent CRT. Advances in radiation-based treatment as reflected in this study have resulted in similar outcomes compared with modern induction C/S. To improve survival, however, newer systemic agents that reduce and control distant metastasis are required.