N2 Nodal Involvement Research Articles

Evaluating Biomarker Dynamics in Breast Cancer Post-Neoadjuvant Chemotherapy: A Retrospective Cross-sectional Study

Background: Neoadjuvant chemotherapy (NACT) is integral to breast cancer management, yet its influence on biomarkers, notably androgen receptor (AR), remains underexplored. This study examines post-NACT alterations in receptor status, including ER, PR AR, HER2 and Ki67 index in breast cancer patients. Methods: A cross-sectional study, spanning three years at a tertiary care center, enrolled patients with invasive breast cancer undergoing mastectomy post-NACT. Pre- and post-NACT specimens underwent histological grading and immunohistochemistry for hormone status, HER2 status, and Ki67 index. Discordance between pre- and post-NACT receptor statuses and expression levels of biomarkers was assessed using McNemar’s and Wilcoxon signed rank tests respectively. Results: Among 100 patients, 35 were assessed. Mean age was 43.83 years, with prevalent T1 tumors (34.3%) and N1 nodal involvement (37.1%). Post-NACT, 54.2% showed no histological grade change. Notable alterations included changes in ER (14.2%), PR (14.2%), and HER2 status (8.57%). AR expression showed a significant change following NACT (p=0.03), while ER expression exhibited a trend towards significance (p=0.06). Ki67 index decreased in only 5.7% of cases. Conclusion: This study unveils intricate biomarker dynamics following NACT in breast cancer, with particular emphasis on AR, hitherto not evaluated. Larger investigations are imperative to elucidate clinical implications and tailor treatment strategies for breast cancer patients undergoing NACT.

What Does N2 Lymph Node Involvement Mean for Patients with Non-Small Cell Lung Cancer (NSCLC)?-A Review of Implications for Diagnosis and Treatment.

Patients with stage III NSCLC with N2 lymph node involvement carry a complex and diverse disease entity. Challenges persist in the areas of diagnosis, staging, multimodal management, and the determination of surgical indications and resectability criteria. Therefore, this review focuses on the latest updates in N2 disease staging and its prognostic and treatment implications. Emphasis is placed on the importance of accurate staging using imaging modalities such as [18F]FDG-PET/CT as well as minimally invasive mediastinal staging endoscopic techniques. The evolving role of surgery in the management of N2 disease is also explored. The benefits of neoadjuvant and adjuvant treatments have been demonstrated, along with the efficacy of a combined multimodal approach with chemo-immunotherapy in the perioperative setting, reigniting the debate of N2 disease subsets and optimal treatment options. Furthermore, this review addresses the controversies surrounding surgical approaches in upfront "borderline" resectable stage III NSCLC as well as the benefits of combined chemoradiotherapy with consolidation immunotherapy for patients with unresectable tumors. In conclusion, personalized diagnostic and treatment approaches tailored to individual patient characteristics, resource availability, and institutional expertise are essential for optimizing outcomes in patients with stage III-N2 NSCLC.

Outcomes with perioperative durvalumab (D) in pts with resectable NSCLC and baseline N2 lymph node involvement (N2 R-NSCLC): An exploratory subgroup analysis of AEGEAN.

8011 Background: In the phase 3 AEGEAN study (NCT03800134), perioperative D + neoadj chemotherapy (CT) vs neoadj CT alone significantly improved the primary EPs of event-free survival (EFS) and pathological complete response (pCR; absence of residual viable tumor [RVT] in resection specimen, incl. primary tumor and sampled lymph nodes) with manageable safety in pts with R-NSCLC (modified ITT [mITT] population). Here, we report exploratory analyses of pts in AEGEAN with baseline N2 nodal status. Methods: Pts with Tx-naïve R-NSCLC (stage II–IIIB[N2]; AJCC 8th ed) were randomized (1:1) to 4 cycles of platinum-based CT plus D 1500 mg IV or placebo (PBO) Q3W before surgery (Sx), followed by D or PBO (Q4W, 12 cycles) after Sx. The mITT population excluded pts with known EGFR/ ALK alterations. Efficacy was assessed in an mITT subpopulation with baseline N2 nodal status (per investigator). Safety was assessed in all N2 R-NSCLC pts who had ≥1 Tx dose. Results: Of 740 pts in the mITT population, 366 (49.5%) had baseline N2 nodal status (D, n = 181; PBO, n = 185). In the N2 subgroup, 83.4% in the D arm and 84.9% in the PBO arm completed 4 cycles of platinum-doublet CT; 77.9% and 77.8%, respectively, had Sx; and 73.5% and 71.9% completed Sx. In the N2 subgroup, similar to the overall mITT population, EFS was prolonged in the D vs PBO arm (HR, 0.63 [95% CI: 0.43–0.90]); rates of pCR (16.6% vs 4.9%; difference, 11.7% [95% CI: 5.6–18.4]) and major pathological response (MPR, ≤10% RVT in primary tumor; 32.6% vs 15.1%; difference, 17.5% [95% CI: 8.8–26.0]) were higher in the D vs PBO arm. While EFS benefit in the D vs PBO arm was similar among pts with single- (HR, 0.61 [95% CI: 0.39–0.94]) or multi-station N2 (HR, 0.69 [95% CI: 0.33–1.38]), pCR benefit was less pronounced in multi-station pts (difference in pCR rate, 13.9% [95% CI: 6.6–21.7] for single-station N2 vs 3.8% [95% CI: –9.2–18.8] for multi-station N2). Among pts in the N2 subgroup who had Sx, similar proportions in the D and PBO arms had open (47.5% vs 50.0%) and minimally invasive procedures (50.4% vs 46.5%); 9.2% vs 11.1% had pneumonectomy (9.2% vs 9.6% in the overall mITT population). Of pts in the N2 subgroup who completed Sx, the proportion with R0 resection in the D vs PBO arm (94.7% vs 91.7%) was similar to that in the overall mITT population. Sx was delayed in a similar proportion who had Sx in the D vs PBO arm (19.9% vs 23.6%, respectively), most commonly for logistical reasons (e.g., scheduling issues). Among 394 pts who received Tx (N2 safety analysis subset; D, n = 200; PBO, n = 194), max grade 3/4 any-cause AEs occurred in 38.5% vs 41.8% in the D and PBO arm, respectively, similar to rates in the overall safety analysis set. Conclusions: With clinically meaningful improvement in efficacy, no adverse impact on Sx outcomes and a manageable safety profile, the addition of perioperative D to neoadj CT remains a potential new Tx option for pts with N2 R-NSCLC. Clinical trial information: NCT03800134 .

Comparative Study of 3D Conformal Radiation Therapy by 3 Fields v/s 5 Fields Treatment Planning Techniques for Head and Neck Cancer

Purpose: The purpose of this study was to compare conventional 3 field versus 5 field treatment planning techniques during 3-dimensional conformal radiotherapy(3D-CRT) in respect of OAR, PTV coverage, treatment response & toxicities in head and neck Cancer. Materials and methods: This study included 50 biopsy proven and registered patients of head and neck cancer. Twenty five patients randomized to each arm. Arm A- 3D- conformal radiotherapy by 3 field delivery technique. Arm B--3D- conformal radiotherapy by 5 field delivery technique. All patients were irradiated on linear accelerator with concurrent chemotherapy in form of 3 weekly Cisplatin. Target volumes and normal structures were manually contoured on the axial slices of the planning CT scan. Patients were evaluated at end of treatment, 1st, 3rd & 6th months follow up visits. Results: At the end of treatment 22 (88%) patient in 3 field and 23 (92%) patients in 5 field had complete response. At 6 months complete response was 76% and 80 % in Arm A and B respectively (p value=0.6836). Grade 3rd xerostomia was seen 12% Vs 4% in Arm A and B respectively ( p value= 0.92 ) Mean V95 was 90.93 for conventional 3 field technique and 93.28 with 5 field technique ( p value=0.08).Conclusion: 5 field 3D-CRT technique can be used to spare parotid and other OAR and better PTV coverage specially in larynx carcinoma , patient with N2 or less nodal involvement and not involving higher neck node level.

Metastatic potential of T1a and T1b non-small cell lung cancer: analysis in the Czech population.

Lung cancer is the most common cause of cancer death in the Czech Republic, in part due to its significant metastatic potential. The aim of this study was to collect real data on the metastatic potential and clinical characteristics of T1a and T1b lung cancer in the Czech population and to investigate potential factors that would predict an increased risk of lymph node metastasis. Prospective-retrospective study conducted at the Department of Surgery of the University Hospital Ostrava during the period from January 1, 2015, to July 31, 2022. The study included patients who underwent lobectomy or bilobectomy for T1a and T1b non-small cell lung carcinoma. Out of a total of 165 patients with T1a and T1b lung carcinoma, 17.6% of patients were confirmed to have metastatic involvement of the lymph nodes (with 9.1% classified as N2 lymph node involvement). The highest percentage of positive lymph nodes was observed in patients with tumors located in the upper left lobe (29.5%) and lower right lobe (23.3%). Adenocarcinoma was the most commonly metastasizing carcinoma, with 21.1% of patients showing positive lymph nodes. Neuroendocrine carcinoma metastasized in 19.4% of cases, while squamous cell carcinoma did so in 6.8% of cases. The cumulative risk of having positive lymph nodes in T1a and T1b adenocarcinoma located in the upper left lobe reached 40.0%, of which the risk of N2 lymph node involvement was 25.0%. T1a/b non-small cell lung cancer exhibits significantly lower metastatic potential than T1c tumors and higher. Adenocarcinoma showed a 3-fold higher metastatic potential than squamous cell carcinoma, indicating the need for increased attention in the treatment of lung adenocarcinoma, especially in tumors localized in the upper left lobe, where a cumulative risk of lymph node metastasis of up to 40% was observed.

Extracapsular extension of pN2 lymph node metastases is not prognostically significant in surgically resected patients with non-small cell lung cancer.

In patients with non-small cell lung cancer (NSCLC) the pathologic lymph node status N2 is a heterogeneous entity, with different degrees of lymph node involvement representing different prognoses. It is speculated whether extra capsular nodal extension may help to define a subgroup with implications on long-term survival. We retrospectively identified 118 patients with non-small cell lung cancer (65 men, 53 women), who were treated between 2013 and 2018 and found to have pathologic N2 lymph node involvement. In all patients lung resection with systematic mediastinal and hilar lymph node dissection was performed with curative intent. In N2 lymph nodemetastases capsules of affected lymph nodes were examined microscopically as to whether extracapsular extension was present. 51 patients (43 %) had extracapsular extension (ENE). Most of these patients (n=35) only had ENE in a single lymph node (69 %). The overall 5-year survival rate was 24.6 % and progression-free survival rate 17.8 %. In the multivariate analysis OS was worse for patients with multiple affected pN2 stations, concurrent N1 metastases, increasing age, and larger tumor size. For the percentage of lymph nodes affected with ENE (of total examined) only a non-significant trend towards worse OS could be observed (p=0.06). Although we could not demonstrate significant prognostic differences between N2 extra capsular nodal involvement within our patient population, other analyses may yield different results. However, clinicians should continue performing thorough lymph nodes dissections in order to achieve local complete resection even in patients with extra capsular tumor spread.

Expression of PD-L1 in triple negative breast cancer

Introduction: The second leading cause of cancer deaths in women is breast cancer. Breast cancer awareness has increased due to mammography screenings. The aim of study is to evaluate the prevalence of PD-L1 expression in TNBC cases and to correlate it with clinicopathological parameters. Method: PDL1 expression is measured by immunohistochemical technique using Dako kits, PD-L1 IHC 22C3 pharm Dx, on 44 paraffin block samples from Duhok municipal labs. If the specimen has a combined positive score (CPS) of 10 or higher, it expresses PD-L1. Age groups, grades, kinds, stages, and PDL1, lymph node involvement are studied. Results: 44 cross-sectional patients, mean and SD (47.7±14) years old. (54.5%) of patients in middle age group, (63.6%) at grade III, majority (88.6%) have IDC type and (75%) have negative PDL1, (63.6%) have KI69 less than 20, (70.5%) at stage T2, and (45.5%) have N1 lymph node involvement. There is significant association between PDL1 and Ki67, (100%) of patients with positive PDL1 have Ki67 more than 20 while (15.2%) of patients with negative PDL1 have Ki67 more than 20. Conclusion: 75% of middle-aged individuals with grade III had negative PDL1. All PDL1-positive patients have Ki67 above 20. Different research employ 1%, 5%, or 10% cutoff values, which affects PDL1.

Lymph Node Metastases in Surgically Resected Solitary Ground-Glass Opacities: A Two-Center Retrospective Cohort Study and Pooled Literature Analysis.

An increasing body of evidence supports the noninferiority of sublobar resection compared with lobectomy in terms of survival for patients with early-stage lung cancer with ground-glass opacities (GGOs). However, few studies have focused on the incidence of lymph node (LN) metastases in these patients. We aimed to analyze N1 and N2 lymph node involvement in patients with non-small cell lung cancer (NSCLC) with GGO components stratified with different consolidation tumor ratio (CTR). We performed two-center studies by retrospectively reviewing a total of 864 patients with NSCLC with semisolid or pure GGO manifestation (diameter≤3cm). Clinicopathologic features and outcomes were analyzed. We also reviewed 35 studies to characterize the patient with NSCLC population with the GGO manifestation. In both cohorts, there was no LN involvement for pure GGO NSCLC, while solid predominant GGO exhibited a relatively high LN involvement rate. On the basis of a pooled literature analysis, the incidence of pathologic mediastinal LN was 0% and 3.8% for pure and semisolid GGOs, respectively. GGO NSCLCs with CTR≤0.5 also had rare LN involvement (0.1%). From two cohorts and pooled literature analysis, LN involvement was not observed in patients with pure GGO, and very few patients with semisolid GGO NSCLC with CTR ≤0.5 had LN involvement, revealing that it may be unnecessary to perform lymphadenectomy for pure GGOs, while mediastinal lymph node sampling (MLNS) is enough for semisolid GGOs with CTR ≤0.5. For the patients with GGO CTR >0.5, mediastinal lymphadenectomy (MLD) or MLNS should be considered.

Management of Resectable Stage III-N2 Non-Small-Cell Lung Cancer (NSCLC) in the Age of Immunotherapy.

Simple SummaryThe treatment of resectable stage III non-small-cell lung cancer with N2 lymph node involvement is usually multimodal and is generally based on neoadjuvant chemotherapy +/− radiotherapy followed by surgery, but the cure rate is still low. Immunotherapy based on anti-PD1/PD-L1 immune checkpoint inhibitors has improved survival in advanced and stage III non-resectable NSCLC patients and is being studied in earlier stages to improve the cure rate of lung cancer. In this article, we review all therapeutic approaches to stage III-N2 NSCLC, analysing both completed and ongoing studies that evaluate the addition of immunotherapy with or without chemotherapy and/or radiotherapy.Stage III non-small-cell lung cancer (NSCLC) with N2 lymph node involvement is a heterogeneous group with different potential therapeutic approaches. Patients with potentially resectable III-N2 NSCLC are those who are considered to be able to receive a multimodality treatment that includes tumour resection after neoadjuvant therapy. Current treatment for these patients is based on neoadjuvant chemotherapy +/− radiotherapy followed by surgery and subsequent assessment for adjuvant chemotherapy and/or radiotherapy. In addition, some selected III-N2 patients could receive upfront surgery or pathologic N2 incidental involvement can be found a posteriori during analysis of the surgical specimen. The standard treatment for these patients is adjuvant chemotherapy and evaluation for complementary radiotherapy. Despite being a locally advanced stage, the cure rate for these patients continues to be low, with a broad improvement margin. The most immediate hope for improving survival data and curing these patients relies on integrating immunotherapy into perioperative treatment. Immunotherapy based on anti-PD1/PD-L1 immune checkpoint inhibitors is already a standard treatment in stage III unresectable and advanced NSCLC. Data from the first phase II studies in monotherapy neoadjuvant therapy and, in particular, in combination with chemotherapy, are highly promising, with impressive improved and complete pathological response rates. Despite the lack of confirmatory data from phase III trials and long-term survival data, and in spite of various unresolved questions, immunotherapy will soon be incorporated into the armamentarium for treating stage III-N2 NSCLC. In this article, we review all therapeutic approaches to stage III-N2 NSCLC, analysing both completed and ongoing studies that evaluate the addition of immunotherapy with or without chemotherapy and/or radiotherapy.

Is Adjuvant Radiochemotherapy Always Mandatory in Patients with Resected N2 Non-Small Cell Lung Cancer?

In patients with non-small cell lung cancer (NSCLC), the pathologic union for international cancer control (UICC) stage IIIA is a heterogeneous entity, with different forms of N2-lymph node involvement representing different prognoses. Although a multimodality treatment approach, including surgery, systemic therapy, and/or radiotherapy, is almost always recommended, in this retrospective observational study, we sought to determine whether long-term survival might be possible in selected patients who are treated with complete surgical resection alone. Between 2013 and 2018, we retrospectively identified 24 patients with NSCLC (16 men and 8 women), who were found to have pathologic N2-lymph node involvement, and were treated with complete surgical lung resection and systematic mediastinal and hilar lymph node dissection but no neoadjuvant or adjuvant treatment. The most frequent reason (n = 14) for forgoing adjuvant treatment was patient refusal. The mean overall survival (OS) was 34.5 months (interquartile range [IQR]: 15.5-53.5 months). The mean disease-free survival (DFS) was 18 months (IQR: 4.75-46.75 months). We identified five patients who survived at least 5 years without recurrence (21%). In each of these cases, the nodal metastases were restricted to a single level and no extracapsular lymph node involvement were detected. Additionally, worse DFS was associated with pT3/4 (vs. a lower T-stage), as well as microscopic lymphovascular invasion. Although the small sample size precludes any definitive conclusions, it was possible to demonstrate that long-term survival without neoadjuvant and adjuvant treatment is possible in some patients if complete tumor and nodal resection is performed.

“Rectal cancer survival: A retrospective analysis of MRI features and their association with prognosis”

PurposeTo assess rectal cancer aggressiveness using magnetic resonance (MR) imaging features and to investigate their relationship with patient prognosis. Materials and methodsClinical information and Pelvic MR scans of 106 consecutive patients with primary rectal cancer (RC) were analyzed. Clinical symptoms, age, sex, tumor location, and patient´s survival were recorded. The variables investigated by MR were: depth or mural/extramural tumor involvement, distance to mesorectal margin, lymph node involvement, vascular, peritoneal or sphincter complex infiltration. The association between imaging features and disease-free survival (DFS) was also assessed using a Kaplan-Meier model. Differences between survival curves were tested for significance using the Mantel-Cox LogRank test. ResultsThe final study population was 106 patients (65 males, 41 females). The median age was 69.5 years (range, 39-92 years). No significant differences were found between death risk and sex, age or tumor location (p>0,05). However, the relative risk (RR) of tumor mortality increased significantly with the presence of the variables: vascular infiltration (×5), T4 tumors (× 4.57), N2 lymph node involvement (more than 3 affected nodes × 4.11) and mesorectal fascia involvement (× 3,77). ConclusionTumor extension, number of pathological lymph nodes, mesorectal fascia involvement and vascular infiltration values obtained on initial MR imaging staging showed a significant difference for disease-free survival in RC at six years of control.

Is sporadic colorectal cancer more aggressive in young people and should the age of colonoscopy screening be reduced?

The present study aims to report the incidence of colorectal cancer patients under 50 years of age and to compare its aggressiveness with colorectal cancer patients over 50 years of age. Recently, the incidence of colorectal cancer at younger ages has increased, and colorectal cancers in young people have a more aggressive course due to late screening programs. The files of patients who were operated for colorectal cancer were reviewed retrospectively. Information on the patients such as gender, age, BMI, type and duration of symptoms, location of the tumor, TNM staging, pathology results, operative procedure, morbidity and mortality rates were recorded. Admission complaints, symptom onset time, tumor locations, pathological findings and tumor stages were compared between patients under and over the age of 50. The incidence of colorectal cancer under 50 was 21 % (56/267). The age group of 40‒49 was found to be the most common age range under the age of 50, with a colorectal cancer rate of 68%. In patients under the age of 50, higher invasion of the tumor to the serosa, low differentiation of the tumor in terms of histological findings in a higher number of patients and higher mucin component of the tumors and higher N2 lymph node involvement ratio and the tumor was located more in the lower rectum were statistically significant when compared to patients over the age of 50 (p=0.026, p=0.018, p=0.002, p=0.042, p=0.006; respectively). The incidence of colorectal cancer has increased at younger ages and has a more aggressive course. Screening programs should be modified (Tab. 4, Fig. 2, Ref. 45).

Predictive Factors for Lymph Node Metastasis in Clinical Stage I Part-Solid Lung Adenocarcinoma

Accurate clinical staging of tumors with a small solid portion is essential for developing an appropriate treatment plan. This study evaluated predictive factors for lymph node (LN) metastasis in patients with clinical stage I part-solid lung adenocarcinoma. Medical records of patients with clinical stage I part-solid adenocarcinoma who underwent anatomic pulmonary resection with systematic node evaluation between January 2009 and June 2018 were retrospectively reviewed. To identify predictive factors for LN metastasis, univariate and multivariable logistic regression analyses were performed. Among the 593 patients in this study, the overall prevalence of LN metastasis was 3.7% (n= 22), which included 3.0% (n= 18) of patients with N1 LN metastasis and 1.5% (n= 9) of patients with N2 LN metastasis. Combined N1 and N2 nodal involvement was observed in 5 patients. Nodal metastasis was not observed in tumors with a solid portion sized 1.1 cm or smaller. The nodal metastasis rates in cT1b, cT1c, and cT2a tumors were 5.5% (13 of 237), 7.1% (6 of 84), and 13.6% (3 of 22), respectively. According to the multivariable analysis, predictive factors included the size of the solid portion (P= .015) and the high maximum standardized uptake value (SUVmax) of the primary tumor (P= .044). Large solid portion and high SUVmax of the primary tumor were predictive factors of LN metastasis in patients with clinical stage I part-solid lung adenocarcinoma. Systematic LN evaluation should be performed, especially in those who have a large solid portion and high SUVmax of the primary tumor.

The Incidence of Node-Positive Non-small-Cell Lung Cancer Undergoing Sublobar Resection and the Role of Radiation in Its Management.

Purpose: To identify the incidence, preoperative risk factors, and prognosis associated with pathologically positive lymph node (pN+) in patients undergoing a sub-lobar resection (SLR).Methods: This is a retrospective study using the National Cancer Database (NCDB) from 2004 to 2014 analyzing SLR excluding those with any preoperative chemotherapy and/or radiation, follow-up <3 months, stage IV disease, or >1 tumor nodule. Multivariable modeling (MVA) was used to determine factors associated with overall survival (OS). Propensity score matching (PSM) was used to determine preoperative risk factors for pN+ in patients having at least one node examined to assess radiation's effect on OS in those patients with pN+ and to determine whether SLR was associated with inferior OS as compared to lobectomy for each nodal stage.Results: A total of 40,202 patients underwent SLR, but only 58.3% had one lymph node examined. Then, 2,615 individuals had pN+ which decreased progressively from 15.1% in 2004 to 8.9% in 2014 (N1, from 6.3 to 3.0%, and N2, from 8.4 to 5.9%). A lower risk of pN+ was noted for squamous cell carcinomas, bronchioloalveolar adenocarcinoma (BAC), adenocarcinomas, and right upper lobe locations. In the pN+ group, OS was worse without chemotherapy or radiation. Radiation was associated with a strong trend for OS in the entire pN+ group (p = 0.0647) which was largely due to the effects on those having N2 disease (p = 0.009) or R1 resections (p = 0.03), but not N1 involvement (p = 0.87). PSM noted that SLR was associated with an inferior OS as compared to lobectomy by nodal stage in the overall patient population and even for those with tumors <2 cm.Conclusion: pN+ incidence in SLRs has decreased over time. SLR was associated with inferior OS as compared to lobectomy by nodal stage. Radiation appears to improve the OS in patients undergoing SLR with pN+, especially in those with N2 nodal involvement and/or positive margins.

Morbi-mortalité de la résection pulmonaire pour cancer par chirurgie vidéo-assistée chez l’octogénaire

Due to an increase in life expectancy, onco-pulmonologists and thoracic surgeons are more frequently faced with octogenarian patients with lung cancer. In this age group, treatment modalities may need to be revised because of the increasing presence of comorbidities. Surgery remains the reference treatment for early stage disease, but mortality rates and postoperative complications are higher in this group of patients. One of the solutions to reduce the operative risk would be to develop videoassisted thoracoscopic pulmonary resection surgery. The aim of this study was to evaluate the results of this form of lung cancer surgery in octogenarians. All patients 80 years old or more who underwent videoassisted lung cancer surgery from 2014 to 2018 at Lyon University Hospital were included. Wedge resections and diagnostic procedures were excluded. Nineteen patients (13 men, 6 women) were included. The median age was 82 years old. All patients had undergone videoassisted lobectomy. Three patients required conversion to thoracotomy (15.8%). All patients underwent complete resection (R0). One patient had N1 lymph node involvement, all others were N0. The postoperative complication rate was 68.4%, the majority of which were grade II of the Clavien classification. Perioperative mortality was 5.3%. Videoassisted lung cancer resection in a selected population of octogenarians is associated with satisfactory short-term results. It is reasonable to favour minimally invasive techniques in this population, even if the proof of their superiority has not yet been firmly established.

Adjuvant and inductive systemic treatment in non-small cell lung cancer

Alarge number of randomized trials have demonstrated an undoubted advantage of adjuvant chemotherapy in comparison to surgery alone. This is true for all lymph node positive cases of non-small cell lung cancer (NSCLC) with a tumor size of 4 cm or more. Worldwide, the application of adjuvant chemotherapy for these indications is regarded as standard treatment. Due to the positive results of adjuvant chemotherapy, nearly all studies focusing on neoadjuvant chemotherapy were stopped early because control arms with surgery alone were no longer regarded as ethically justified; however, in meta-analyses the effect of neoadjuvant chemotherapy seems be as strong as the effect of adjuvant chemotherapy. In clinical practice neoadjuvant chemotherapy is not routinely established in early stage disease. This approach is more often applied in advanced stages, such as N2 lymph node involvement or in patients where the tumor most probably requires pneumectomy for resection. In the last decade the options for systemic treatment of NSCLC have dramatically changed. In addition to chemotherapy, targeted treatment of patients with molecularly altered tumors and immunotherapy have been used very successfully in advanced stages. The options might also have ahigh impact on survival in early stages and the integration of these treatment modalities in the management of early stage disease is warranted. This article summarizes the established and new options in additive systemic treatment and presents the current state of treatment.

ES23.02 Which N2 Patients Are Candidates to Surgery in the Era If I/O?

The role of surgery in patients with pre-resection documented N2 disease remains a subject of controversy. In some institutions, any clinical N2 disease identified preoperatively is considered non-surgical and these patients are offered upfront definitive chemoradiation therapy (DefCRT) without planned resection. In other institutions, a selective approach to N2 patients will consider surgery as part of a multimodality approach where surgery may be offered first followed by adjuvant cytotoxic chemotherapy (AC) with or without sequential post-operative radiation therapy (PORT), or where surgery will be offered after induction chemotherapy or induction chemoradiation therapy. Due to variability in N2 disease presentation, factors determining this selective approach vary between institutions and may include the bulk of N2 nodal involvement (size), extent of N2 involvement (single vs multistation, microscopic vs macroscopic), the presence or absence of extracapsular nodal involvement, the need to perform a pneumonectomy or not, and mediastinal sterilization after induction therapy. Historically, response to induction therapy with clearance of N2 nodal involvement following induction therapy has been shown to bode for a better prognosis after surgical resection. Unfortunately, even after complete resection following induction therapy, many patients develop distant metastases, with brain metastases prevailing. In 2018, the PACIFIC trial showed that adding an immune checkpoint inhibitor (IO) durvalumab for up to one year after completion of DefCRT in non-surgical stages cIIIa and cIIIB patients led to a significant and unprecedented overall survival in this population of patients. (Antonia, NEJM 2018) In patients with resectable NSCLC (cIIIA and less), recent small phase I clinical trials of either single-agent induction IO (Forde, NEJM 2018) or concurrent induction chemoimmunotherapy (Provencio, JTO abst. 2018) given before surgery have demonstrated feasibility, acceptable toxicity, and unprecedented pathological response rates. It remains to be seen if these pathologic responses will translate into improved overall survival in this patient population. Extrapolating from these early observations, one may think that induction IO (likely with concurrent cytotoxic chemotherapy) may possibly allow us to offer surgery to a larger proportion of patients with clinical N2 disease in the future as we observe higher response rates to induction therapies which may translate in better survival. Others may want to extrapolate from the Pacific trial results and hypothesize that surgery followed by adjuvant IO may become a desirable option. Though encouraging, there is a paucity of data to help guide us in the incorporation of IO therapy perioperatively for patients with clinical N2 disease. As such, the role for IO in multimodality treatment for N2 disease remains undefined. Unknown are the true impacts of periop IOs in this patient population and what is the optimal combination and timing of these multimodality treatments. There are more unanswered questions than established guidelines: (1) whether “IO first then surgery” is superior to “surgery first then adjuvant IO”, (2) whether an induction IO strategy followed by resection would be superior to DefCRT followed by IO in this population of potentially resectable cN2 IIIA patients, (3) if induction IO is shown to be superior, how many cycles preop, (4) do we need to continue IOs post op, if so, for how long, (5) whether there will be a role for surgery after major response to IO, and (6) how will we select patients for resection when major pathological response rates will be in the 80% range (7) do we need to utilize biomarkers, tumor mutation burden, or genotyping in patient selection, (8) What is the best biomarker to predict response, among other questions . The easy answer at this stage is to treat these patients on trials where the impact of IOs can be rigorously studied. Ideally, I personally would want to compare: (1) Induction vs adjuvant IOs for surgical patients with cN+ disease, (2) Induction IO followed by resection vs DefCRT followed by IO. The duration of periop IO also needs to be evaluated and these studies should include cost analysis as well. For the surgeons, as systemic treatments improve, our duty is to perform sound oncological surgery with minimal morbidity and minimal to absent mortality. I believe that preop IO may allow us to consider surgical resection for a larger proportion of cIIIA N2 patients in the future. Immunotherapy, stage IIIA NSCLC, surgery

Systemic Inflammation-Immune Status Predicts Survival in Stage III-N2 Non-Small Cell Lung Cancer

Systematic inflammation-immune status has been thought to play a crucial role in tumorigenesis and progress. This study evaluated the prognostic value of systematic inflammation-immune status in patients with resected non-small cell lung cancer with pathological N2 nodal involvement (pN2-NSCLC). The relation between the preoperative systematic inflammation-immune score (SIS), defined as preoperative peripheral platelet count× neutrophil count/lymphocyte count, and prognosis was tested in a retrospective study of 660 consecutive patients with completed resected pN2-NSCLC and validated by a prospective study of 189 patients enrolled (NCT00880971). SIS of 650× 109 was an optimal cutoff point to stratify the patients with pN2-NSCLC into high (>650× 109) and low (≤650× 109) SIS groups in the training cohort. Univariate and multivariate analyses revealed that the SIS was an independent predictor for overall survival, disease-free survival, and distant metastasis-free survival. In the validation group, high SIS (>650× 109) predicted poor 5-year overall survival (hazard ratio [HR], 2.418; P=.006), disease-free survival (HR, 1.542; P= .042), and distant metastasis-free survival (HR, 1.682; P= .024). In addition to the number of positive lymph nodes, the area under the receiver operating characteristic curve of the SIS for outcomes was higher than the neutrophil count-to-lymphocyte count ratio, platelet count-to-lymphocyte count ratio, and other conventional clinicopathologic indices. The preoperative SIS is a more sensitive survival predictor than most of the other conventional clinical indices and may aid in more accurately stratifying patients for risk assessment and treatment decision.

Prognostic significance of the pattern of pathological N1 lymph node metastases for non-small cell lung cancer.

In patients with non-small cell lung cancer (NSCLC) the pathologic lymph node status N1 is a heterogeneous entity, and different forms of lymph node involvement may represent different prognoses. For methodological reasons, the 8th edition of the TNM staging system for NSCLC makes no official changes to the N descriptor. However, there is evidence that different subforms of N1 disease are associated with different prognoses, and it is now recommended that clinicians record the number of affected lymph nodes and nodal stations for further analyses. In this investigation we sought to determine whether patients with different levels and types of N1 lymph node involvement had significantly different 5-year survival rates. We retrospectively identified 90 patients with NSCLC (61 men, 29 women), who were treated between 2008 and 2012 and found to have pathologic N1 lymph node involvement and tumor sizes corresponding to T1 or T2. All patients were treated in curative intent with surgical lung resection and systematic mediastinal and hilar lymph node dissection. The overall 5-year survival rate was 56.3%. In the univariate analysis, lower tumor stage and tumor histology other than large-cell carcinoma were significantly associated with better long-term survival. Patients with solitary lymph node metastases also had longer disease-free survival than those with multiple nodal metastases. In the multivariate analysis, large-cell carcinoma and Union for International Cancer Control (UICC) stage IIB were independently associated with worse survival, while pneumonectomy, compared to lobar or sublobar resection, was independently associated with better survival. Although we did not observe significant prognostic differences between N1 subcategories within our patient population, other analyses may yield different results. Therefore, these data highlight the need for large, well-designed multicenter studies to confirm the clinical significance of N1 subcategories.

Combined Endosonographic Mediastinal Lymph Node Staging in Positron Emission Tomography and Computed Tomography Node-Negative Non–Small-Cell Lung Cancer in High-Risk Patients

Positron emission tomography (PET) with computed tomography (CT) is routinely utilized to investigate lymph node (LN) metastases in non-small-cell lung cancer. However, it is less sensitive in normal-sized LNs. This study was performed in order to define the prevalence of mediastinal LN metastases discovered on combined endosonography by endobronchial ultrasound (EBUS) and endoscopic ultrasound (EUS) fine needle aspiration in patients with a radiologically normal mediastinum. This study consists of a retrospective, single-institution, tertiary care referral center review of a prospectively maintained database. Patients were identified from a cohort between January 2009 and December 2014. One hundred and sixty-one patients with biopsy-proven, non-small-cell lung cancer were identified in whom both the preendosonography CT and PET-CT were negative for mediastinal LN metastases. Combined endosonography (EBUS + EUS-FNA) was performed in all patients. Z test was used for statistical analysis. A P value of <0.05 was considered statistically significant. A total of 161 consecutive patients were included. Patients were staged if they had central tumor, tumor size >3 cm, N1 lymph node involvement on PET-CT/CT, or if there was low SUV (<2.5) in the primary tumor. A total of 416 lymph nodes were biopsied in the 161 patients using combined endosonography; 147 with EBUS and 269 with EUS. Mean and median number of lymph nodes biopsied per patient using combined EBUS/EUS was 2.5 and 3, respectively (mean and median EBUS: 0.91 and 2.5; mean and median EUS 1.6 and 3). Endosonographic staging upstaged 13% of patients with radiologically normal lymph nodes in the mediastinum, hilum, lobar, and sublobar regions (confidence interval 8.22-19.20). Twenty-one out of 161 patients (13%) with radiologically normal mediastinum were positive on combined EBUS/EUS staging. Out of 21 patients upstaged on endosonography, 15 (71%) had tumor size >3 cm. Six (28%) had occult N1 disease. Thirteen (61%) had occult N2 disease and 2 (9%) had adrenal involvement. None of the upstaged patients had N1 LN involvement on PET-CT or CT scan. Combined endosonographic lymph node staging should be considered in the pretreatment staging of high-risk patients with non-small-cell lung cancer in the presence of radiologically normal mediastinal lymph nodes due to the significant rate of radiologically occult lymph node metastases.