Impact of intrapulmonary tumour location of non-small-cell lung cancer on surgical outcomes for segmentectomy.

OBJECTIVES: While segmentectomy is considered a viable option for small peripheral non-small-cell lung cancer, its efficacy for central lesions remains uncertain. This study aimed to assess the oncological outcomes of segmentectomy for central lesions compared to peripheral ones. METHODS: We retrospectively examined 338 clinical stage IA non-small-cell lung cancer patients who underwent thoracoscopic anatomical segmentectomy at our institution from January 2013 to December 2021. Patients were divided into 2 groups based on intrapulmonary tumour location: inner two-thirds (central group, n = 82) and outer one-third (peripheral group, n = 256). RESULTS: The gender, body mass index, performance score, smoking, comorbidities and preoperative pulmonary function were similar in both groups. On computed tomography images, tumour diameter and consolidation-to-tumour ratio were comparable between the groups. The central group had significantly greater tumour-to-pleura distances [mm, 23 (18-27) vs 11 (8-14); P < 0.001], shorter margin distances [mm, 20 (15-20) vs 20 (20-20); P < 0.001] and larger resected lung volumes based on subsegment count [4 (3-6) vs 3 (3-5); P = 0.004] than the peripheral group. Surgery duration, bleeding, hospitalization or drainage period, mortality, readmission and pathological stage were equivalent between the groups. The central group showed significantly more postoperative pleural effusions (5% vs 1%; P = 0.03) than the peripheral group, with no adverse impact on postoperative pulmonary functions. During the follow-up period, local-only recurrence rates were 0% and 8% in the respective groups (Gray test P = 0.07), and total recurrence rates were 6% and 11% (Gray test P = 0.70), with no significant differences. Moreover, no significant inter-group difference in overall survival rates was observed (82% vs 93%; P = 0.15). CONCLUSIONS: Segmentectomy may be a promising therapeutic option for early-stage non-small-cell lung cancer located in the inner two-thirds of the parenchyma.

NOTCH1 and CREBBP co-mutations negatively affect the benefit of adjuvant therapy in completely resected EGFR-mutated NSCLC: translational research of phase III IMPACT study.

The phase III IMPACT study (UMIN000044738) compared adjuvant gefitinib with cisplatin plus vinorelbine (cis/vin) in completely resected epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). Although the primary endpoint of disease-free survival (DFS) was not met, we searched for molecular predictors of adjuvant gefitinib efficacy. Of 234 patients enrolled in the IMPACT study, 202 patients were analyzed for 409 cancer-related gene mutations and tumor mutation burden using resected lung cancer specimens. Frequent somatic mutations included tumor protein p53 (TP53; 58.4%), CUB and Sushi multiple domains 3 (CSMD3; 11.8%), and NOTCH1 (9.9%). Multivariate analysis showed that NOTCH1 co-mutation was a significant poor prognostic factor for overall survival (OS) in the gefitinib group and cAMP response element binding protein (CREBBP) co-mutation for DFS and OS in the cis/vin group. In patients with NOTCH1 co-mutations, gefitinib group had a shorter OS than cis/vin group (Hazard ratio 5.49, 95% CI 1.07-28.00), with a significant interaction (P for interaction = 0.039). In patients with CREBBP co-mutations, the gefitinib group had a longer DFS than the cis/vin group, with a significant interaction (P for interaction = 0.058). In completely resected EGFR-mutated NSCLC, NOTCH1 and CREBBP mutations might predict poor outcome in patients treated with gefitinib and cis/vin, respectively.

Neoadjuvant nivolumab plus chemotherapy in resectable non-small-cell lung cancer in Japanese patients from CheckMate 816.

In the open-label, phase III CheckMate 816 study (NCT02998528), neoadjuvant nivolumab plus chemotherapy demonstrated statistically significant improvements in event-free survival (EFS) and pathological complete response (pCR) versus chemotherapy alone in patients with resectable non-small-cell lung cancer (NSCLC). Here we report efficacy and safety outcomes in the Japanese subpopulation. Patients with stage IB-IIIA, resectable NSCLC were randomized 1:1 to nivolumab plus chemotherapy or chemotherapy alone for three cycles before undergoing definitive surgery within 6 weeks of completing neoadjuvant treatment. The primary end-points (EFS and pCR) and safety were assessed in patients enrolled at 16 centers in Japan. Of the Japanese patients randomized, 93.9% (31/33) in the nivolumab plus chemotherapy arm and 82.9% (29/35) in the chemotherapy arm underwent surgery. At 21.5 months' minimum follow-up, median EFS was 30.6 months (95% confidence interval [CI], 16.8-not reached [NR]) with nivolumab plus chemotherapy versus 19.6 months (95% CI, 8.5-NR) with chemotherapy; hazard ratio, 0.60 (95% CI, 0.30-1.24). The pCR rate was 30.3% (95% CI, 15.6-48.7) versus 5.7% (95% CI, 0.7-19.2), respectively; odds ratio, 7.17 (95% CI, 1.44-35.85). Grade 3/4 treatment-related adverse events were reported in 59.4% versus 42.9% of patients, respectively, with no new safety signals identified. Neoadjuvant nivolumab plus chemotherapy resulted in longer EFS and a higher pCR rate versus chemotherapy alone in Japanese patients, consistent with findings in the global population. These data support nivolumab plus chemotherapy as a neoadjuvant treatment option in Japanese patients with resectable NSCLC.

Divided method of intercostal nerve block reduces ropivacaine dose by half in thoracoscopic pulmonary resection while maintaining the postoperative pain score and 4-h mobilization: a retrospective study.

PURPOSE: This study investigated whether the divided method of multi-level intercostal nerve block (ML-ICB) could reduce the ropivacaine dose required during thoracoscopic pulmonary resection, while maintaining the resting postoperative pain scores. METHODS: This retrospective, single-cohort study enrolled 241 patients who underwent thoracoscopic pulmonary resection for malignant tumors between October 2020 and March 2022 at a cancer hospital in Japan. ML-ICB was performed by surgeons under direct vision. The differences in intraoperative anesthetic use and postoperative pain-related variables at the beginning and end of surgery between group A (single-shot ML-ICB; 0.75% ropivacaine, 20 mL at the end of the surgery) and group B (divided ML-ICB, performed at the beginning and end of surgery; 0.25% ropivacaine, 30 mL total) were assessed. The numerical rating scale (NRS) was used to evaluate pain 1 h and 24 h postoperatively. RESULTS: Intraoperative remifentanil use was significantly lower in group B (14.4 ± 6.4 µg/kg/h) than in group A (16.7 ± 8.4 µg/kg/h) (P = 0.02). The proportion of patients with NRS scores of 0 to 3 at 24 h was significantly higher in group B (85.4%, 106/124) than in group A (73.5%, 86/117) (P = 0.02). The proportion of patients not requiring postoperative intravenous rescue drugs was significantly higher in group B (78.2%, 97/124) than in group A (61.5%, 72/117) (P < 0.01). CONCLUSION: The divided method of ML-ICB could reduce the intraoperative remifentanil dose, decrease the postoperative pain score at 24 h, and curtail postoperative intravenous rescue drug use, despite using half the total ropivacaine dose intraoperatively.

Thoracoscopic Anatomical Sublobar Resection Including Subsegmentectomy for Non-Small Cell Lung Cancer.

BACKGROUND: Among anatomical sublobar resection techniques for non-small cell lung cancer (NSCLC), the clinical benefit of subsegmentectomy remains unclear. We investigated whether anatomical sublobar resection including subsegmentectomy-segmental resection with subsegmental additional resection or subsegmental resection alone-is an effective and feasible surgical procedure for NSCLC. METHODS: We retrospectively reviewed data of 285 patients with clinical stage I NSCLC who underwent anatomical sublobar resection at our institution from January 2013 to March 2021 and compared surgical outcomes between patients who underwent anatomical sublobar resection including (IS; n = 50) and excluding (ES; n = 235) subsegmentectomy. RESULTS: No significant intergroup differences were noted in terms of age, sex, smoking, comorbidities, tumor size or location, consolidation tumor ratio, and preoperative pulmonary function. The IS group had more preoperative computed tomography-guided markings (34 vs. 15%; p = .004) and smaller resected lung volumes converted to the total subsegment number [3 (2-4) vs. 3 (3-6); p = .02] than the ES group. No significant differences in margin distance [mm, 20 (15-20) vs. 20 (20-20); p = .93], readmission rate (2% vs. 3%; p > .99), and intraoperative (8% vs. 7%; p = .77) or postoperative (8% vs. 10%; p = .80) complication rates were observed, and the 5-year local recurrence-free survival (91% vs. 90%; p = .92) or postoperative pulmonary function change were comparable between both groups. CONCLUSIONS: Although further investigations are required, anatomical sublobar resection including subsegmentectomy for clinical stage I NSCLC could be an acceptable therapeutic option.

Port Placement Variations for Robotic Lung Resection: Focusing on Their History, Conventional Look-Up-View and Horizontal Open-Thoracotomy-View Techniques, and More.

This is a narrative review that summarizes the variations in approaches and port placements used for performing robotic lung resections on the da Vinci Surgical Platforms. Currently, the four-arm, look-up-view method, in which the intrathoracic cranial side is viewed from the caudal side, is considered the mainstream approach worldwide. Several variations were devised from this conventional technique, including the so-called horizontal open-thoracotomy-view techniques in which the intrathoracic craniocaudal axis is aligned with the horizontal direction of the console monitor, and fewer port and incision techniques. In September 2022, 166 reports were surveyed using a PubMed English literature search, and this review finally included 30 reports describing the approaches. We categorized the variations into four-phase groups considering advent histories: (I) early era, three-arm technique with utility incisions; (II) four-arm, total port technique without robotic staplers; (III) four-arm technique using robotic staplers; (IV) maximizing the functional features of the Xi, significant alterations in viewing directions, and reducing ports, including the ultimate uniport technique. To comprehensibly visualize these variations for practical use, we created elaborate illustrations based on the literature. The familiarity of thoracic surgeons with the variations and characteristics allows them to choose the optimal procedure that best suits each patient and their preferences.

Three-Arm Robotic Lung Resection via the Open-Thoracotomy-View Approach Using Vertical Port Placement and Confronting Monitor Setting: Focusing on Segmentectomy.

To perform robotic lung resections with views similar to those in thoracotomy, we devised a vertical port placement and confronting upside-down monitor setting: the three-arm, robotic "open-thoracotomy-view approach (OTVA)". We described the robotic OTVA experiences focusing on segmentectomy and its technical aspects. We retrospectively reviewed 114 consecutive patients who underwent robotic lung resections (76 lobectomies and 38 segmentectomies) with OTVA using the da Vinci Xi Surgical System between February 2019 and June 2022. To identify segmental boundaries, we administered indocyanine green intravenously and used the robotic fluorescence imaging system (Firefly). In all procedures, cranial-side intrathoracic structures, which are often hidden in the conventional look-up-view method, were well visualized. The mean durations of surgery and console operation were 195 and 140 min, respectively, and 225 and 173 min, for segmentectomy and lobectomy, respectively. In segmentectomy, console operation was significantly shorter (approximately 30 min, p < 0.001) and two more staplers (8.2 ± 2.3) were used compared with lobectomy (6.6 ± 2.6, p = 0.003). In both groups, median postoperative durations of chest tube placement and hospitalization were 0 and 3 days, respectively. This three-arm robotic OTVA setting offers natural thoracotomy views and can be an alternative for segmentectomy and lobectomy.

Postoperative surveillance using low-dose computed tomography for non-small-cell lung cancer.

OBJECTIVES: We retrospectively analysed the surgical prognosis of patients with pathological stage I non-small-cell lung cancer (NSCLC) who after complete resection underwent low-dose computed tomography (LDCT) or conventional CT as postoperative surveillance. METHODS: We investigated 416 patients who underwent lobectomy or segmentectomy between January 2013 and December 2016. We compared the prognosis between the LDCT and conventional CT groups using the propensity score-matched analysis. RESULTS: The median follow-up period was 57 months. Cancer recurrence occurred in 47 patients (11.3%). In the entire cohort (n = 416), recurrence-free survival (RFS) and overall survival (OS) were better in the LDCT group (P = 0.001 and 0.002, respectively). Both intrathoracic recurrence and distant metastasis were higher in the conventional group (P = 0.015 and 0.009, respectively). However, there was no statistical difference in the factors leading to recurrence detection (routine radiological examination, symptoms and elevated tumour markers: all P > 0.05). Both groups were matched using a ratio of 1:1. The area under the receiver operating characteristic curve was 0.788. A total of 226 patients were successfully matched. After matching, there was no statistical difference between the 2 groups for RFS and OS (P = 0.263 and 0.226). There were also no statistical differences in recurrence rate, the factors leading to recurrence detection or recurrence site (all P > 0.05). CONCLUSIONS: After using propensity score matched, RFS and OS did not differ significantly between LDCT and conventional CT groups. Retrospective comparisons suggest no disadvantages of using LDCT for postoperative surveillance of pathological stage I NSCLC. Further validation will be needed in the future.

Synchronous driver gene alterations (EGFR L858R, T790M, and ROS1) rearrangements in a patient with early-stage lung adenocarcinoma.

Concurrent EGFR mutation and ROS1 rearrangement is a rare event in early-stage non-small-cell lung cancer. In addition, a co-occurring de novo EGFR T790M mutation in such a case is extremely rare. We encountered a 72-year-old woman who developed 3 early-stage lung lesions synchronously, one each harboring EGFR L858R, ROS1 rearrangement, and EGFR L858R and de novo T790M. These three nodules were pathologically time-matched lepidic predominant adenocarcinoma with small invasive lesions, which may reflect the concept of field cancerization with driver mutations.

Preoperative percutaneous needle indigo carmine and lipiodol mixture marking in lung segmentectomy.

OBJECTIVES: For successful nodule localization and appropriate surgical margin distances in pulmonary segmentectomy for patients with lung malignancies, the effectiveness and feasibility of preoperative marking using an indigo carmine and lipiodol mixture remain unclear. METHODS: Patients who underwent thoracoscopic pulmonary segmentectomy with (marking group, n = 69) and without (non-marking group, n = 265) preoperative marking at our institution from January 2013 to March 2020 were retrospectively reviewed and compared in terms of surgical outcomes. All markings were performed using a fine needle to percutaneously inject an indigo carmine and lipiodol mixture under the guidance of computed tomography fluoroscopy. RESULTS: Successful localization was achieved in 66 (96%) patients, of whom 62 (94%) underwent dye pigmentation and 4 (6%) underwent intraoperative fluoroscopy. On images, the marking group showed a significantly longer distance between the lung surface and tumour [mm, 9 (1-17) vs 0 (0-10); P < 0.01] and smaller maximum tumour size [mm, 16 (11-21) vs 17 (13-23); P = 0.03] and consolidation tumour ratio [0.4 (0.3-1) vs 0.8 (0.4-1); P < 0.01] than the non-marking group. Both groups had comparable operative outcomes, perioperative complications, pulmonary function changes and surgical margin distances [mm, 20 (15-21) vs 20 (15-20); P = 0.96] without any local recurrence on the surgical margin. Propensity score-matching analysis also showed similar findings for both groups. CONCLUSIONS: Thoracoscopic pulmonary segmentectomy with preoperative marking using an indigo carmine and lipiodol mixture may be an acceptable therapeutic option for small malignancies located in deep lung parenchyma.

New evaluation of the tumor immune microenvironment of non-small cell lung cancer and its association with prognosis.

BACKGROUND: A better understanding of the tumor immune microenvironment (TIME) will facilitate the development of prognostic biomarkers and more effective therapeutic strategies in patients with lung cancer. However, little has been reported on the comprehensive evaluation of complex interactions among cancer cells, immune cells, and local immunosuppressive elements in the TIME. METHODS: Whole-exome sequencing and RNA sequencing were carried out on 113 lung cancers. We performed single sample gene set enrichment analysis on TIME-related gene sets to develop a new scoring system (TIME score), consisting of T-score (tumor proliferation), I-score (antitumor immunity) and S-score (immunosuppression). Lung cancers were classified according to a combination of high or low T-score, I-score, and S-scores (eight groups; G1-8). Clinical and genomic features, and immune landscape were investigated among eight groups. The external data sets of 990 lung cancers from The Cancer Genome Atlas and 76 melanomas treated with immune checkpoint inhibitors (ICI) were utilized to evaluate TIME scoring and explore prognostic and predictive accuracy. RESULTS: The representative histological type including adenocarcinoma and squamous cell carcinoma, and driver mutations such as epidermal growth factor receptor and TP53 mutations were different according to the T-score. The numbers of somatic mutations and predicted neoantigens were higher in Thi (G5-8) than Tlo (G1-4) tumors. Immune selection pressure against neoantigen expression occurred only in Thi and was dampened in Thi/Ilo (G5-6), possibly due to a reduced number of T cells with a high proportion of tumor specific but exhausted cells. Thi/Ilo/Shi (G5) displayed the lowest immune responses by additional immune suppressive mechanisms. The T-score, I-score and S-scores were independent prognostic factors, with survival curves well separated into eight groups with G5 displaying the worst overall survival, while the opposite group Tlo/Ihi/Slo (G4) had the best prognosis. Several oncogenic signaling pathways influenced on T-score and I-scores but not S-score, and PI3K pathway alteration correlated with poor prognosis in accordance with higher T-score and lower I-score. Moreover, the TIME score predicted the efficacy of ICI in patients with melanoma. CONCLUSION: The TIME score capturing complex interactions among tumor proliferation, antitumor immunity and immunosuppression could be useful for prognostic predictions or selection of treatment strategies in patients with lung cancer.

Randomized Phase III Study of Gefitinib Versus Cisplatin Plus Vinorelbine for Patients With Resected Stage II-IIIA Non-Small-Cell Lung Cancer With EGFR Mutation (IMPACT).

PURPOSE: To investigate the efficacy of gefitinib as an adjuvant therapy for non-small-cell lung cancer patients with EGFR mutation. PATIENTS AND METHODS: IMPACT (WJOG6410L; University Hospital Medical Information Network Clinical Trials Registry: UMIN000006252), a randomized, open-label, phase III study, included patients with completely resected pathologic stage II-III non-small-cell lung cancer harboring EGFR mutations (exon 19 deletion or L858R) during September 2011 to December 2015. Patients were randomly assigned to receive gefitinib (250 mg once daily) for 24 months or cisplatin (80 mg/m2 on day 1) plus vinorelbine (25 mg/m2 on days 1 and 8; cis/vin) once every 3 weeks for four cycles. The primary end point was disease-free survival (DFS). RESULTS: Overall, 234 patients were randomly assigned. Among 232 eligible patients (116 each; excluding two who withdrew consent), the median DFS was 35.9 and 25.1 months in the gefitinib and cis/vin groups, respectively. However, Kaplan-Meier curves crossed around 4 years after surgery with no statistically significant difference (stratified log-rank P = .63; hazard ratio by stratified Cox proportional hazards model = 0.92; 95% CI, 0.67 to 1.28). Overall survival (OS) was also not different (stratified log-rank P = .89; hazard ratio = 1.03; 95% CI, 0.65 to 1.65), with the 5-year OS rates being 78.0% and 74.6% in the gefitinib and cis/vin groups, respectively. Treatment-related deaths occurred in 0 and three patients in the gefitinib and cis/vin groups, respectively. CONCLUSION: Although adjuvant gefitinib appeared to prevent early relapse, it did not prolong DFS or OS. However, similar DFS and OS may justify adjuvant gefitinib in the selected patient subsets, especially those deemed ineligible for platinum-doublet adjuvant therapy; however, this was not a noninferiority trial.

Emergency rollout and conversion procedures during the three-arm robotic open-thoracotomy-view approach.

OBJECTIVES: To conduct robotic lung resections (RLRs) with views similar to those in open-thoracotomy surgery (OTS), we adopted a vertical port placement and confronting upside-down monitor setting: the robotic open-thoracotomy-view approach (OTVA). We herein discuss the procedures for emergency rollout and conversion from the robotic OTVA to OTS or video-assisted thoracoscopic surgery (VATS). METHODS: We retrospectively reviewed the cases of 88 patients who underwent RLR with three-arm OTVA using the da Vinci Xi Surgical System between February 2019 and July 2021. Robotic ports were vertically placed along the axillary line, and 2 confronting monitors and 2 assistants were positioned on each side of the patient. Three possible conversions were prepared: (i) emergency thoracotomy using an incision along the ribs in a critical situation, (ii) cool conversion using vertical incision thoracotomy in a calmer condition and (iii) conversion to confronting VATS. All staff involved in the surgery repeatedly rehearsed the emergency rollout in practice. RESULTS: No emergent or cool conversion to OTS occurred. Two patients (2.3%) experienced confronting VATS conversions. One patient underwent an urgent conversion for a moderate haemorrhage from a pulmonary artery branch during left upper lobectomy in the introduction phase. Another patient underwent a calmer conversion during an extended RS6 + S10a segmentectomy, where staples could not be inserted appropriately due to lung lacerations. In all patients, postoperative courses were uneventful. CONCLUSIONS: The OTVA setting is a possible option for RLRs. This report describes the emergent rollout and subsequent conversion procedures for this method.

Intraoperative Multimodal Approach for Pain After Thoracoscopic Pulmonary Resection.

BACKGROUND: The optimal preemptive analgesia for thoracoscopic surgery remains unclear. We evaluated the utility of intraoperative intravenous analgesia on postoperative pain and the postoperative course in patients who underwent thoracoscopic lobectomy. METHODS: We retrospectively reviewed 228 consecutive patients who underwent single-lobe thoracoscopic lobectomy for malignant pulmonary tumors between October 2017 and December 2019. Instead of epidural anesthesia, intercostal nerve blocks were performed from the thoracic cavity. We assessed the differences in the clinical and perioperative parameters including postoperative pain among the following: (1) N group (nonintraoperative intravenous analgesia), (2) A group (1000 mg acetaminophen), and (3) AF group (1000 mg acetaminophen with 50 mg flurbiprofen axetil). The numerical rating scale (NRS) was used to assess pain. RESULTS: Receiver operating characteristic curve analysis revealed that the optimal cutoff pain score for the additional analgesic within 12 h postsurgery was 3.5 (area under the curve = 0.771; sensitivity = 63%; specificity = 19.4%; 95% confidence interval [CI] = 0.703-0.839; p < 0.01). Less pain scores on the surgical day were related to the AF group (NRS; N, 3 ± 2.6; A, 3 ± 2.4; AF, 2 ± 1.9; p = 0.008, respectively). No pain or mild pain (NRS = 0-2) on the operative day was strongly associated with the AF group (N = 36.4%; A = 46.4%; AF = 70.5%; p = 0.005). None of the patients experienced complications associated with intraoperative intravenous analgesia. CONCLUSION: The combined use of intravenous analgesics (acetaminophen and flurbiprofen axetil) and intercostal nerve blocks is a safe and feasible preemptive analgesic approach for thoracoscopic lobectomy.

Permissible Outcomes of Lobe-Specific Lymph Node Dissection for Elevated Carcinoembryonic Antigen in Non-Small Cell Lung Cancer.

Background and Objectives: Lobe-specific nodal dissection (L-SND) is currently acceptable for the dissection of early-stage non-small cell lung cancer (NSCLC) but not for cancers of more advanced clinical stages. We aimed to assess the efficacy of L-SND, compared to systemic nodal dissection (SND). Materials and Methods: We retrospectively collected the clinical data of patients with carcinoembryonic antigen (CEA) abnormality who underwent complete resection of NSCLC via lobectomy or more in addition to either SND or L-SND at two cancer-specific institutions from January 2006 to December 2017. Results: A total of 799 patients, including 265 patients who underwent SND and 534 patients who underwent L-SND, were included. On multivariate analysis, thoracotomy, more than lobectomy, cN1-2, advanced pathological stage, adjuvant treatment, and EGFR or ALK were strongly associated with SND. No significant differences were found in overall survival, disease-free survival, and overtime survival after propensity adjustment (p = 0.09, p = 0.11, and p = 0.50, respectively). There were no significant differences in local (p = 0.16), regional (p = 0.72), or distant (p = 0.39) tumor recurrence between the two groups. Conclusions: SND did not improve the prognosis of NSCLC patients with CEA abnormality. Complete pulmonary resection via L-SND seems useful for NSCLC patients with CEA abnormality.

Positive Correlation Between the Number of Circulating Tumor Cells in the Pulmonary Vein and Tumor Spread Through Air Spaces in Resected Non-small Cell Lung Cancer.

BACKGROUND/AIM: Circulating tumor cells (CTCs) is one of the promising markers that predict dissemination and metastases. This study aimed to identify the relationship between CTCs in pulmonary vein (PuV) and spread through air space (STAS) in non-small cell lung cancers. MATERIALS AND METHODS: We applied a cytology-based microfluidic platform for rare cell isolation. Twenty-four patients were enrolled. RESULTS: The rate of CTC detection in PuV was 79.2%, and STAS was observed in 54.2% of the samples. When the definitive cut-off value was 1 CTC/1 ml, of the 14 CTC-PuV-high cases, 11 (78.6%) were STAS-positive, whereas 2 of the 10 (20.0%) CTC-PuV-low cases were STAS-positive, and the difference between the two groups was statistically significant (p=0.02). CTC-PuV-high exhibited a significantly poorer survival (p<0.01). CONCLUSION: The higher frequency of STAS is significantly associated with a higher number of CTCs in PuV, and the combination of STAS and CTC was significantly associated with poor prognosis.

Prognostic Radiological Tools for Clinical Stage IA Pure Solid Lung Cancer.

In this study, we analyzed prognostic radiological tools and surgical outcomes for radiologically pure solid adenocarcinomas (AD) and squamous cell carcinoma (SQ) in clinical stage IA. We retrospectively investigated 130 patients who underwent surgical resections. We assessed the predictive risk factors for recurrence and pathological lymph node metastasis (LNM). There was no statistical difference in recurrence free survival (RFS) or cancer-specific survival (CSS) between AD and SQ groups (p = 0.642 and p = 0.403, respectively). In the whole cohort, tumor size on lung window and mediastinal settings, and tumor disappearance ratio using high-resolution computed tomography (HRCT) were not prognostic parameters (p = 0.127, 0.066, and 0.082, respectively). The maximal standardized uptake value (SUVmax) using positron emission tomography-CT was associated with recurrence (p = 0.016). According to the receiver operating characteristic curve, the cut-off value of SUVmax for recurrence was 4.6 (p = 0.016). The quantitative continuous variables using any radiological tools were not associated with LNM. However, tumor diameter on mediastinal setting ≥8 mm with SUVmax ≥2.4 could be a risk factor for LNM. Pure solid AD and SQ were equivalent for the RFS and CSS. SUVmax was useful to predict recurrence. The tumor diameter on a mediastinal setting and SUVmax were useful in predicting pathological LNM.

Survival benefit of immune checkpoint inhibitor monotherapy in patients with non-small cell lung cancer recurrence after completely pulmonary resection.

BACKGROUND: Selected patients in non-small cell lung cancer (NSCLC) responded to the treatment of immune checkpoint inhibitors (ICIs) have the survival benefit for advanced stages or metastatic status. METHODS: We investigated whether a response to ICI monotherapy since 2016 influences the survival of NSCLC patients with recurrence after completely pulmonary resection between 2009 and 2017. Disease control rate (DCR) was calculated as complete plus partial response plus stable disease during more than 6 months. RESULTS: Thirty-five patients (mean age 67 years, range 46-79 years, 60% male) were included in the study. The most frequent histology and pathological stage were adenocarcinoma (60%) and IIB (45.7%), respectively. ICI was used at a median of second-line treatment. The DCR and median progression-free survival were 42.8% and 2.5 (95% CI: 1.6-3.4) months, respectively. The therapeutic outcome from recurrence was 47.5%. Multivariate analysis revealed a significant impact of DCR on favorable therapeutic outcome (P=0.04). A serial increase (pre- to post-surgery to ICI initiation) of C-reactive protein (CRP) and prognostic nutritional index (PNI) was associated with treatment response (both P=0.01). CONCLUSIONS: These results suggest that a response to ICI monotherapy significantly contributes to a survival benefit regardless of therapeutic lines in NSCLC patients with recurrence after completely pulmonary resection, and the therapeutic response is strongly associated with a serial increase in CRP or decrease in prognostic nutritional index.