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.

Efficacy of the Segment-Counting Method in Predicting Lung Function and Volume Following Stapler-Based Thoracoscopic Segmentectomy.

PURPOSE: To investigate the accuracy of a segment-counting method in predicting lung function and volume after stapler-based thoracoscopic segmentectomy in comparison with lobectomy. METHODS: Between 2014 and 2018, patients who underwent these procedures were retrospectively reviewed. Thoracic computed tomography and spirometry data before and 1 year after the surgery were assessed. We evaluated the differences between the predicted values using a segment-counting method and the actual postoperative values for lung function and volume in each group. Sub-analyses were also performed to assess the impact of the number of staples and resected segments in predicting patient outcomes. RESULTS: We included 116 patients (segmentectomy, 69; lobectomy, 47). Actual postoperative lung function and volume values matched the predicted values in the stapler-based segmentectomy group, and significantly exceeded the predictions in the lobectomy group (P <0.01). Sub-analyses revealed lower postoperative lung function values than predicted existed after single segmentectomy, with an odds ratio of 3.29 (95% confidence interval: 1.02-10.70, P = 0.04) in a multivariable analysis. The degree of predicted error regarding lung function was negligible. CONCLUSIONS: The segment-counting method was useful in predicting lung function after stapler-based thoracoscopic segmentectomy. Segmentectomy rarely yielded lower-than-predicted lung function and volume values.

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.

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.

Robotic open-thoracotomy-view approach using vertical port placement and confronting monitor setting.

OBJECTIVES: Robotic lung resections (RLRs) are conventionally performed using look-up views of the thorax from the caudal side. To conduct RLR with views similar to those in open thoracotomy, we adopted a vertical port placement and confronting upside-down monitor setting, which we called robotic 'open-thoracotomy-view approach'. We herein present our experience of this procedure. METHODS: We retrospectively reviewed 58 patients who underwent RLR (43 with lobectomy; 15 with segmentectomy) with 3-arm open-thoracotomy-view approach using the da Vinci Surgical System between February 2019 and October 2020. The patient cart was rolled in from the left cranial side of the patient regardless of the side to be operated on. Robotic ports were vertically placed along the axillary line, and 2 confronting monitors and 2 assistants were positioned on each side of the patient. The right-side monitor, which was set up for the left-side assistant to view, projected the upside-down image of the console surgeon's view. RESULTS: All procedures were safely performed. The median duration of surgery and console operation was 215 and 164 min, respectively. Emergency conversion into thoracotomy and severe morbidities did not occur, and the median postoperative hospitalization duration was 3 days. In all procedures, the console surgeon and 2 assistants had direct 'bird-eye' views of the cranially located intrathoracic structures and instrument tips, which are sometimes undetectable with the conventional look-up view. CONCLUSIONS: The open-thoracotomy-view approach setting is a possible option for RLR. It offers natural thoracotomy views and can circumvent some of the known limitations of the conventional procedure.

[Recurrence of a Giant Retroperitoneal Leiomyosarcoma Six Years after the Initial Surgery].

A 51-year-old man came to our department because of a large abdominal mass. CT, MRI, and sonography revealed a large tumor adjacent to the retroperitoneal area. A resection was performed, and histologically we confirmed the diagnosis as a leiomyosarcoma originating from the retroperitoneum. Six years after the initial surgery, the patient came to our outpatient department with a complaint of nausea. A relatively large tumor was seen on a CT scan that was causing obstruction of the duodenum. Another surgery was performed with the final diagnosis as a recurrence of the leiomyosarcoma. After 3 courses of adjuvant chemotherapy with eribulin, the patient presented with abdominal distension. CT revealed a very large tumor with massive invasion to the ileum and colon. This time, we considered the tumor unresectable, and administered chemotherapy with a combination of doxorubicin and ifosfamide. However, after 1 course, the patient's condition worsened and he died of the disease 3 months after the chemotherapy.