Stage IIIA Non-small Cell Lung Research Articles

Lung autotransplantation combined with postoperative chemotherapy and immunotherapy: a three-year follow-up case report

BackgroundLung cancer remains a leading cause of cancer-related mortality worldwide. Autotransplantation has emerged as a potential surgical intervention in select cases, with the aim of achieving curative outcomes. This case report describes a novel approach combining lung autotransplantation with postoperative chemotherapy and immunotherapy, delineating the patient's journey over a period of three years.Case presentationWe report on a 37-year-old patient with stage IIIA non-small cell lung cancer (NSCLC) who underwent lung autotransplantation. Despite the complexity of the procedure, the patient had a favorable postoperative course. Adjuvant therapy included a PD-1 inhibitor and a standard chemotherapy regimen. The patient’s follow-up involved regular clinical assessment, imaging, and functional status evaluation, demonstrating a remarkable disease-free survival at the three-year mark postoperatively.ConclusionThis case highlights the potential for lung autotransplantation coupled with immunotherapy and chemotherapy to yield significant long-term survival benefits in patients with NSCLC. The favorable outcome suggests that this integrative treatment strategy warrants further investigation and may offer hope to patients with similarly advanced lung cancer.

Predicting therapeutic response to neoadjuvant immunotherapy based on an integration model in resectable stage IIIA (N2) non-small cell lung cancer

ObjectiveAccurately predicting response during neoadjuvant chemoimmunotherapy for resectable non-small cell lung cancer (NSCLC) remains clinically challenging. In this study, we investigate the effectiveness of blood-based tumor mutational burden (bTMB) and a deep learning (DL) model in predicting major pathologic response (MPR) and survival from a phase II trial. MethodsBlood samples were prospectively collected from 45 stage IIIA (N2) NSCLC patients undergoing neoadjuvant chemoimmunotherapy. An integrated model, combining the CT-based DL score, bTMB, and clinical factors, was developed to predict tumor response to neoadjuvant chemoimmunotherapy. ResultsAt baseline, bTMB were detected in 77.8% (35 of 45) of patients. Baseline bTMB ≥11 Muts/Mb was associated with significantly higher MPR rates (77.8% vs. 38.5%, p = 0.042), and longer disease-free survival (DFS, p = 0.043), but not overall survival (p = 0.131), compared to bTMB < 11 Muts/Mb in 35 patients with bTMB available. The developed DL model achieved an area under the curve (AUC) of 0.703 in all patients. Importantly, the predictive performance of the integrated model improved to an AUC of 0.820 when combining the DL score with bTMB and clinical factors. Baseline circulating tumor DNA (ctDNA) status was not associated with pathological response and survival. Compared to ctDNA residual, ctDNA clearance before surgery was associated with significantly higher MPR rates (88.2% vs. 11.1%, p < 0.001) and improved DFS (p = 0.010). ConclusionsThe integrated model shows promise as a predictor of tumor response to neoadjuvant chemoimmunotherapy. Serial ctDNA dynamics provide a reliable tool for monitoring tumor response.

Longitudinal quality of life after sublobar resection and stereotactic body radiation therapy for early-stage non-small cell lung cancer.

Many patients with early-stage lung cancer are not candidates for lobectomy because of various factors, with treatment options including sublobar resection or stereotactic body radiation therapy (SBRT). Limited information exists regarding patient-centered outcomes after these treatments. Subjects with stage I-IIA non-small cell lung cancer (NSCLC) at high risk for lobectomy who underwent treatment with sublobar resection or SBRT were recruited from five medical centers. Quality of life (QOL) was compared with the Short Form 8 (SF-8) for physical and mental health and Functional Assessment of Cancer Therapy-Lung (FACT-L) surveys at baseline (pretreatment) and 7 days, 30 days, 6 months, and 12 months after treatment. Propensity score methods were used to control for confounders. Of 337 subjects enrolled before treatment, 63% received SBRT. Among patients undergoing resection, 89% underwent minimally invasive video-assisted thoracic surgery or robot-assisted resection. Adjusted analyses showed that SBRT-treated patients had both higher physical health SF-8 scores (difference in differences [DID], 6.42; p=.0008) and FACT-L scores (DID, 2.47; p=.004) at 7 days posttreatment. Mental health SF-8 scores were not different at 7 days (p=.06). There were no significant differences in QOL at other time points, and all QOL scores returned to baseline by 12 months for both groups. SBRT is associated with better QOL immediately posttreatment compared with sublobar resection. However, both treatment groups reported similar QOL at later time points, with a return to baseline QOL. These findings suggest that sublobar resection and SBRT have a similar impact on the QOL of patients with early-stage lung cancer deemed ineligible for lobectomy.

NEOADJUVANT CHEMORADIOTHERAPY IN THE MULTIMODALITY TREATMENT OF STAGE IIIA(N2) NON-SMALL CELL LUNG CANCER (NSCLC)

Summary. The choice of optimal treatment for stage IIIA(N2) non-small cell lung cancer (NSCLC) remains controversial, since the five-year survival rate of this category of patients cannot meet modern medical requirements and patient expectations even after radical surgery and chemotherapy (CT). Accordingly, the analysis of available clinical data and the search for the most effective multimodal treatment option are constantly ongoing. The main treatment strategy for stage IIIA(N2) NSCLC is surgery with induction CT. As part of a comprehensive clinical approach, neoadjuvant CT (NCT) is used to eliminate distant micrometastases, leading to increased survival in an independent operation. Meanwhile, induction with concurrent chemoradiotherapy (CRT) followed by surgery resulted in a 30% to 40% improvement in 5-year survival. Aim: to evaluate the results of treatment of patients with stage IIIA(N2) NSCLC after the use of various methods of neoadjuvant and adjuvant therapy in case of surgical intervention. Object and methods: the effect of NCRT was performed in 37 patients with stage IIIA(N2) NSCLC in selected tumors of the lungs and the middle of the National Cancer Institute. This group of patients was planned for multimodal treatment, which included 3 or 4 cycles of chemotherapy with platinum-based drugs following the regimens of cisplatin + docetaxel or carboplatin + paclitaxel with one-hour radiotherapy (RT), consisting of sessions in the or classical fractionation with a single dose of 2 Gy, SOD up to 50 Gy with subsequent surgery. The number of CT cycles (3 or 4) depended on the result of the control observation of the dynamics of regression of the tumor process. In the core of the vicoristan group, there was the first control group of stage IIIA(N2) NSCLC patients with NCT (n = 194). This group of patients was given 3 or 4 courses of CT using a regimen similar to the main group: cisplatin / carboplatin + docetaxel / paclitaxel, and in the second control group – similar to the number of courses and drugs, neoadjuvant CT and RT in SOD 50 Gy in adjuvant regimen (n = 60) with further surgical treatments. All patients, depending on the prevalence of the tumor process, underwent radical surgery in the form of lobectomy, bilobectomy or pneumonectomy with mediastinal lymphodissection. Results: median survival in the main group was 30.12 months, in the first control group (NCT) – 23.68 months and the second control group (NCT + adjuvant RT) – 23.23 months, respectively. In the main group, 5 (14.7%) patients were diagnosed with a complete morphological response of the primary tumor and a complete morphological response of the tumor tissue in the regional lymph nodes. In addition to the complete morphological response of the primary tumor and metastatic mediastinal lymph nodes (tumor cells were not detected in histological preparations), in 5 (14.7%) cases, a pronounced morphological response of a highly differentiated tumor was detected (residual viability of tumor tissue to 12±5%). These patients had a higher median survival (45 and 39 months, respectively) compared to controls. Conclusion: the treatment regimen with NCRT is more promising for increasing patient survival.

EP08.02-34 Evaluation of Treatment Strategies for Patients with Stage IIIA Non-Small Cell Lung Cancer in the Immunotherapy Era

EP08.02-34 Evaluation of Treatment Strategies for Patients with Stage IIIA Non-Small Cell Lung Cancer in the Immunotherapy Era

Effectiveness comparison of third-generation EGFR-TKI as initial and sequential therapy in adjuvant treatment for EGFR mutation-sensitive stage IIIA non-small cell lung cancer after surgery

IntroductionAlthough third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) Osimertinib has been approved as adjuvant therapy for resected stage IIIA non-small cell lung cancer (NSCLC) with EGFR-sensitive mutations, the optimal treatment sequencing of EGFR-TKIs, particularly whether Osimertinib should be the initial or sequential therapy following the first-generation EGFR-TKIs remains uncertain. MethodsA retrospective analysis was conducted on a cohort of patients with EGFR-mutated stage IIIA NSCLC who received treatment with either first-generation EGFR-TKIs or Osimertinib (third-generation) alone, or in sequential combination, at a single institution. The data analysis involved using the Kaplan-Meier method, log-rank test, and Cox regression. ResultsOut of the total 148 patients with stage IIIA NSCLC included in the study, 76 individuals underwent treatment with either first-generation EGFR-TKIs (referred to as subgroup “1″) or exclusively Osimertinib (subgroup “0 + 3″), or a sequential combination of the two (subgroup “1 + 3″) following surgery. Both univariate and multivariate analyses demonstrated that there were no discernible disparities in terms of disease-free survival and overall survival between subgroup " 1″ and " 1 + 3,” nor between subgroup " 0 + 3″ and “1 + 3". ConclusionThe findings from this study indicate that the introduction of third-generation EGFR-TKI Osimertinib did not yield enhanced survival benefits when compared to the first-generation drug in patients with stage IIIA completely resected NSCLC who were administered EGFR-TKIs as part of their postoperative adjuvant treatment. Additionally, within the observed sample size of this cohort, the sequential use of Osimertinib alongside first-generation EGFR-TKI did not demonstrate superiority over using either the first-generation EGFR-TKI or Osimertinib alone in terms of postoperative survival.

Stage IIIA Non-Small Cell Lung Cancer Treatment and Outcomes: A Single Institution Retrospective Analysis

Treatment of locally advanced non-small cell lung cancer (NSCLC) remains challenging, with a multitude of treatment options available for Stage III patients. We hypothesized that Stage IIIA outcomes differ by treatment received. We performed a retrospective review of NSCLC patients ≥18 years old with Stage IIIA disease treated 1/1/2010-03/01/2022. Demographics, treatment received, treatment outcomes, and failure patterns were collected. Progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier analysis. Kruskal-Wallis ANOVA was used to compare groups. Of 352 patients identified, 160 had Stage IIIA NSCLC with a median follow-up of 29.1 months. Patients had a median age of 63 years, 79 (49.4%) were male, and 137 (85.6%) were current/former smokers (with 30 median pack-years). Patients were treated as follows: 17 (11%) surgery alone (S), 91 (57%) definitive radiation ± chemotherapy (CRT), 52 (33%) neoadjuvant therapy followed by surgery (Neo). 6 (12%) of the Neo group received chemoimmunotherapy, and 21 (51%) of the 41 CRT patients received adjuvant immunotherapy. Between the three groups, there were no significant differences in tumor size as measured by T-staging (p = 0.83) and baseline FEV1/FVC (p = 0.92). Median PFS was 33.5mo (95% CI 13.2-NA) for group S, 18.4mo (95% CI 12.7-42.2) for CRT, and 19.7mo (95% CI 13.9-NA) for Neo with no significant intergroup difference (p = 0.72). Median OS was 33.5mo (95% CI 13.2-NA) for S, 48.7mo (95% CI 36.0-88.9) for CRT, and 50.9mo (95% CI 41.9-NA) for Neo with no significant intergroup difference (p = 0.94). Among the 17 primary surgical patients, 11 (65%) experienced failure: 6 (35%) local, 5 (29%) regional, and 7 (41%) distant. Among the 91 CRT patients, 57 (63%) experienced failure: 40 (44%) local, 35 (38%) regional, and 28 (31%) distant. Among the 52 Neo patients, 26 (50%) experienced failure: 14 (27%) local, 15 (29%) regional, and 17 (33%) distant. There were no significant differences in rates of local failure (p = 0.26), regional failure (p = 0.59), distant failure (p = 0.79), or any failure (p = 0.41) among the three treatment groups. The most common locations for distant failure were pleural effusions (n = 15, 29%), CNS (n = 14, 27%), and bone (n = 11, 21%). In this single institution retrospective study, we find no significant differences in PFS, OS, and failure patterns between patients with Stage IIIA NSCLC treated with definitive (chemo)radiation and neoadjuvant therapy. Numeric improvement in PFS in surgery-only patients is consistent with expected patient selection of this group. Further work in the immunotherapy era is needed.

Long-Term Outcomes of Selected Patients with IIIA-N2 Non-small Cell Lung Cancer Receiving Upfront Surgical Resection.

Stage IIIA non-small cell lung cancer (NSCLC) is a diverse group that requires multimodality treatment. The aim of this study was to report the long-term outcomes for patients with IIIA-N2 disease. We conducted a retrospective review of cases with IIIA-N2 (T1-2N2) NSCLC who underwent upfront surgery. Kaplan-Meier curves and Cox proportional hazard analyses were used to assess the impact of various variables on survival. A total of 475 patients were ultimately included. With a median follow-up time of 108 months, the 5- and 10-year overall survival (OS) rates were 42.2% and 27.7%, respectively. R0 resection was found to be associated with improved progression-free survival (PFS) and OS compared with R1/R2 resection (p=0.041 for PFS; p=0.015 for OS). Patients with single-station N2 disease demonstrated significantly better PFS and OS than those with multiple-station N2 disease (p<0.001 for PFS; p=0.002 for OS). Following surgical resection, adjuvant therapy was significantly correlated with prolonged PFS and OS compared with those patients without any treatment. However, there was no significant difference in PFS and OS between chemotherapy and radiochemotherapy (p=0.915 for PFS; p=0.287 for OS). Patients with EGFR exon 19 deletion had significantly improved OS compared with those with L858R (p=0.040). Our study shows promising long-term outcomes for selected patients with stage IIIA-N2 NSCLC treated with upfront surgery followed by adjuvant therapy, especially those with R0 resection and single-station N2. This study sheds light on the potential management and treatment options for this challenging population.

Neoadjuvant Camrelizumab Plus Platinum-Based Chemotherapy vs Chemotherapy Alone for Chinese Patients With Resectable Stage IIIA or IIIB (T3N2) Non–Small Cell Lung Cancer

The benefit of neoadjuvant camrelizumab plus chemotherapy for resectable stage IIIA or IIIB non-small cell lung cancer (NSCLC) remains unknown. To assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy vs chemotherapy alone for patients with resectable stage IIIA or IIIB NSCLC. In this randomized phase 2 clinical trial conducted at 2 hospitals in China, patients aged 18 to 70 years with resectable stage IIIA or IIIB (T3N2) NSCLC were enrolled between April 7, 2020, and January 12, 2022. Patients were randomly assigned to receive 3 cycles of camrelizumab (200 mg) plus chemotherapy (nab-paclitaxel, 130 mg/m2, and platinum [cisplatin, 75 mg/m2; carboplatin, area under the curve, 5; or nedaplatin, 100 mg/m2]) or chemotherapy alone, followed by surgery after 4 to 6 weeks. The primary end point was the pathologic complete response (pCR) rate. Secondary end points included the major pathologic response (MPR) rate, objective response rate (ORR), event-free survival (EFS), and safety. Disease-free survival (DFS, defined as the time from surgery to disease recurrence or death from any cause) was analyzed post hoc. Efficacy was assessed on a modified intention-to-treat basis. Ninety-four Chinese patients were randomized, and 88 (93.6%; median age, 61 years [IQR, 54-65 years]; 74 men [84.1%]) received allocated neoadjuvant treatment (43 received camrelizumab plus chemotherapy, and 45 received chemotherapy alone). Among these 88 patients, the pCR rate was 32.6% (14 of 43; 95% CI, 19.1%-48.5%) with camrelizumab plus chemotherapy vs 8.9% (4 of 45; 95% CI, 2.5%-21.2%) with chemotherapy alone (odds ratio, 4.95; 95% CI, 1.35-22.37; P = .008). The MPR rates were 65.1% (95% CI, 49.1%-79.0%) with camrelizumab plus chemotherapy and 15.6% (95% CI, 6.5%-29.5%) with chemotherapy alone. The radiographic ORRs were 72.1% (95% CI, 56.3%-84.7%) with camrelizumab plus chemotherapy and 53.3% (95% CI, 37.9%-68.3%) with chemotherapy alone. With a median follow-up of 14.1 months (IQR, 9.2-20.9 months), the median EFS and DFS were not reached in either group. The most common neoadjuvant treatment-related adverse events of grade 3 or higher were decreased white blood cell count (6 of 43 [14.0%] in the camrelizumab plus chemotherapy group vs 2 of 45 [4.4%] in the chemotherapy group) and decreased neutrophil count (3 of 43 [7.0%] in the camrelizumab plus chemotherapy group vs 5 of 45 [11.1%] in the chemotherapy group). No treatment-related deaths were reported. This randomized clinical trial found that among patients with resectable stage IIIA or IIIB (T3N2) NSCLC, camrelizumab plus chemotherapy, compared with chemotherapy alone, significantly improved the pCR rate with manageable toxic effects. ClinicalTrials.gov Identifier: NCT04338620.

The prognosis of clinical stage IIIa non-small cell lung cancer in Taiwan.

Lung cancer is the leading cause of cancer death. The treatment of stage IIIa remained the most controversial of all stages of non-small cell lung cancer (NSCLC). We reported on the heterogenicity and current treatment strategies of stage IIIa NSCLC in Taiwan. This study is a retrospective analysis using data from the Taiwan Society of Cancer Registry between January 2010 and December 2018. 4232 patients with stage IIIa NSCLC were included. Based on cell type, the best 5-year OS (40.40%) occurred among adenocarcinoma victims. The heterogenicity of T1N2 had the best 5-year OS (47.62%), followed by T4N0 (39.82%), and the others. Patients who underwent operations had better 5-year OS (over 50%) than those who did not (less than 30%). Segmentectomy (75.28%) and lobectomy (54.06%) showed better 5-year OS than other surgical methods (less than 50%). In multivariable analysis, young age, female, lower Charlson Comorbidity Index score, adenocarcinoma cell type, well differentiated, T1N2/T4N0 heterogenicity, treatment with operation, and segmentectomy/lobectomy/bilobectomy were significant factors. In conclusions, the heterogenicity of T1N2 had the best outcomes followed by T4N0. Patients received surgical treatment revealed much better outcomes than those did not. As always, multimodal therapies with individualized treatment tend to provide better survival outcomes.

Alectinib-induced rash unresponsive to desensitization: a case report and literature review

BackgroundSince the inception of targeted therapies in treating lung cancer, providers have had to be aware of a new host of side effects when selecting management options for patients. Although targeted therapies are creating increased hope for patients with non-small cell lung cancers (NSCLC), understanding their side effects presents a challenge for providers. Alectinib, a second-generation tyrosine kinase inhibitor, is a targeted therapy used in patients with non-small cell lung cancer found to have anaplastic lymphoma kinase (ALK) mutations. Alectinib is the focus of this case report and literature review as we seek to understand side effects providers may encounter when prescribing these therapies.Case presentationWe begin our report with the case of a 63-year-old Hispanic female with stage IIIA non-small cell lung cancer found to have the ALK genomic alteration. She was started on Alectinib, and on Day 11, she developed a severe maculopapular rash requiring hospitalization. After complete resolution, desensitization with Alectinib was attempted but unsuccessful.ConclusionsDespite the unsuccessful desensitization of this patient, it is important to report this rare side effect in order to better understand how providers can pursue management. Case reports such as this can aid providers in potentially preventing, treating, and rechallenging patients on targeted therapies in the future.

Five-year survival of resectable stageIIIA non-small cell lung cancer in Brazil.

In stageIIIA non-small cell lung cancer (NSCLC), surgery plays a role in terms of multimodal treatment. Surgery rates have increased in recent years, mainly due to the combination of more accurate imaging tools, electromagnetic navigation bronchoscopy, robotic bronchoscopy, robotic surgery, and a wide range of challenging clinical scenarios to lead surgeons and oncologists to include surgery as an option in therapeutic management. To assess the prognostic factors, the 5-year overallsurvival (OS) and cancer-specific survival (CSS) of patients with resectable stageIII-NSCLC. Patients'information was extracted from 76 Hospitals'Cancer Registry. OSand CSS were constructed using the Kaplan-Meier method, and the log-rank test was used to assess differences between curves. In addition, Cox regression was conducted to evaluate the patients'characteristics leading to better OS and CSS. Overall, 433 stageIII NSCLC surgical patients followed over 19 years were included. The median age was 61.29 ± 9.62 years, 58.4% male, 50.1% with adenocarcinoma, 29.3% with squamous cell carcinoma, 3.7% with large-cell lung carcinoma, and 16,9% with other lung cancer types. The 5-year OS was 30.6% (95% confidence interval [CI]: 27.4-36.1), and the CSS was 35.0% (95%CI: 29.4-41.0). In the Cox multivariate regression, squamous cell carcinoma was associated with reduced OS (hazard ratio [HR]: 1.40; 95%CI: 1.07-1.83; p=0.014) and CSS (HR: 1.56; 95%CI: 1.17-2.08; p = 0.002), in comparison with adenocarcinoma. The 2015-2019 quinquennial had a 50% reduction in HR (0.49; 95%CI: 0.29-0.81; p = 0.006), and the 2010-2014 group had a 40% reduction (0.59; 95%CI: 0.42-0.83; p = 0.006) in comparison with the 2000-2004 patients'group. The OS and CSS of patients with resectable stageIII NSCLC have improved over the past 19 years in our region. Squamous cell carcinoma was associated with increased mortality risk from any cause or specific cancer.

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, &lt; 0.001) but lower than other races including Asians (0.77, 0.69-0.87, &lt; 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, &lt; 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 &gt; 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 &lt; $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.

Prospective Feasibility and Phase 1/2 Trial of Preoperative Proton Beam Therapy With Concurrent Chemotherapy for Resectable Stage IIIA or Superior Sulcus Non-Small Cell Lung Cancer

This is the first prospective clinical trial (NCTXXXX) evaluating proton beam therapy (PBT) with concurrent chemotherapy as part of trimodality management for resectable stage IIIA or superior sulcus non-small cell lung cancer (NSCLC). The starting PBT dose level was 50.4 Gy in 1.8 Gy fractions (feasibility study), followed by sequential dose escalation to determine maximum tolerated dose (MTD) of PBT based on dose-limiting toxicities (DLTs) (phase I/II study). DLTs were defined as 30-day postoperative mortality, grade ≥4 hematologic toxicity requiring >14-day treatment breaks, or any grade ≥3 non-hematologic/esophagitis/pneumonitis toxicities attributable to PBT. Primary outcomes included feasibility, MTD, and pathologic complete response (pCR) rate. Twenty patients underwent neoadjuvant PBT and chemotherapy, of which 19 subsequently underwent surgery. There were 13 patients in the feasibility study (at 50.4 Gy) and 6 in the phase I/II study (at 59.4 Gy). The trial closed early due to slow accrual prior to reaching the MTD. Treatment was deemed feasible. There were no DLTs, including no post-operative deaths within 30 days. Two patients (10%) experienced PBT-related acute grade 3 adverse events (post-operative atrial fibrillation and esophagitis/dysphagia); no grade 4-5 acute non-hematologic adverse events were noted. Overall and nodal pCR rates were 5/19 (26%) and 8/18 (44%), respectively; nodal pCR was 4/13 (31%) at 50.4 Gy versus 4/5 (80%) at 59.4 Gy (p=0.12). Median follow-up was 8.5 years. Median and 5-year progression-free survival were 1.8 years and 25%, and median and 5-year overall survival were 3.6 years and 40%, respectively. Eleven patients experienced disease failure, most with a distant component (10 of 11). Concurrent PBT and chemotherapy is feasible as part of trimodality management with favorable oncologic outcomes and low toxicity rates.

NCCN Highlights Best Practices for Challenges in Oncology

NCCN Highlights Best Practices for Challenges in Oncology

116P Survival outcome of chemotherapy in stage IIIA and IIIB non-small cell lung cancer

116P Survival outcome of chemotherapy in stage IIIA and IIIB non-small cell lung cancer

307P Differential expression profiling of transcripts in stage IIIA non-small cell lung cancer (NSCLC) of smokers and non-smokers cases of north India: A geneto-environmental study

Several epidemiological and experimental studies suggest that the etiology of many chronic illnesses is caused by the joint effect between genetics and the environment. Smoking tobacco is the major hazard feature for lung cancer in Indian subcontinent especially men, compare to woman where, other important risk factors i.e., exposure to agents and level of pollutions are responsible. So, the aim of the study is to compare the expression level of transcript-based biomarkers IDH1, CEA, Cyfra21-1, and TPA in NSCLC fifty tumor tissue stage IIIa patients compared to control benign tissues of smokers and non-smokers cases living in areas with air quality categorized as poor (AQI 201–300) or moderate (AQI 101–200).

State of the art and new perspectives in surgical treatment of lung cancer: a narrative review.

Lung cancer is the leading cause of cancer-related deaths worldwide, and its incidence has increased over the past two decades. The standard care for stage I, stage II, and selected cases of stage IIIA non-small cell lung cancer (NSCLC) is surgical resection; in some cases, patients may be offered adjuvant systemic therapy after surgical resection. Patients with lung cancer presenting with distant metastases belong to stage IV: in this setting, some carefully selected patients may benefit from surgery within a multimodality approach. We performed a comprehensive, non-systematic review of the latest literature to define the present role of surgery in lung cancer treatment. The literature review disclosed a pivotal role of surgery in early stage lung cancer and a complimentary role in locally advanced lung cancer; in very selected cases, surgery might be considered in oligometastatic disease. Surgical treatment of lung cancer still plays a pivotal role in early stages of the disease while, in locally advanced stages, it may contribute to improve overall survival in combination with medical treatments and radiotherapy. More recently, an effective role of surgery has been advocated in carefully selected oligometastatic patients with encouraging initial results.

Adjuvant radiation therapy improves survival in stage IIIA (N2) non-small cell lung cancer with persistent N2 disease after neoadjuvant chemotherapy

ObjectivesRole of adjuvant radiation therapy in stage III (N2) non-small cell lung cancer has been controversial over the decades. Recent large, randomized trials have demonstrated that adjuvant radiation did not improve overall survival or disease-free survival; however, the trials either excluded or enrolled very few cases that have undergone neoadjuvant chemotherapy. Role of adjuvant radiation after neoadjuvant chemotherapy remains unclear. Whether the use of adjuvant radiation is associated with improved overall survival in those who have received neoadjuvant chemotherapy, especially in a subgroup of patients with persistent N2, is unknown. Materials and methodsPatients with clinical stage III (N2) non-small cell lung cancer diagnosed from 2004 through 2017 were queried to National Cancer Database. Eligibility criteria included completely resected (R0), pathological diagnosis, neoadjuvant multi-agent chemotherapy, information regarding post-surgical N2 status (persistent versus downstaged to pN0-1), adjuvant radiation (45 Gy+ versus none), and American Joint Commission on Cancer staging version (6th versus 7th). Those who have received neoadjuvant radiation with any dose or adjuvant radiation with less than 45 Gy total dose were excluded. Kaplan-Meier and log-rank tests were used for survival analyses. Propensity-score matching analysis was used for validation. All statistical analyses were two-sided, and p < 0.05 was required for statistical significance. ResultsA total of 1,855 patients met the eligibility criteria for analysis. In the overall cohort, there was a significant difference in overall survival between persistent N2 (Cohort P: N = 854, median survival 50.7 months) and downstaged N (Cohort D: N = 1,001, median survival 82.7 months). The use of adjuvant radiation showed a non-significant detrimental effect in overall survival in the overall and Cohort D (univariate p-values 0.27 and 0.077, respectively); however, both univariate and multivariate analyses demonstrated a significant improvement in overall survival in Cohort P (p = 0.004 and 0.028, respectively). These findings are also verified by propensity-score matching analysis (p = 0.0347). ConclusionsThis large-scale retrospective analysis suggests that adjuvant radiation may still have a role in persistent N2 disease after neoadjuvant chemotherapy. Further investigations are warranted.

Chirurgie beim nichtkleinzelligen Lungenkarzinom im Stadium III N2 innerhalb multimodaler Konzepte

Stage IIIA non-small cell lung cancer comprises an inhomogeneous group of patients with both locoregional (N1) and ipsilateral mediastinal (N2) lymph node metastasis. Close collaboration between surgeons, thoracic oncologists, and radiotherapists allows selected patients to be offered multimodal treatment with curative intent despite N2 metastasis. Individual outcomes can be further improved by integration of novel multimodal treatment options into established therapeutic strategies. Targeted therapies and antibodies for checkpoint inhibition have already gained entry into standard adjuvant lung cancer treatment. Promising results of ongoing phase III trials investigating neoadjuvant chemoimmunotherapy highlight the necessity of reviewing the role of immunomodulatory drugs in the context of operable lung cancer. Approval of corresponding agents for perioperative systemic treatment of patients with nonmetastatic lung cancer is expected in the near future.