Small lung tumor biopsy samples are feasible for high quality targeted next generation sequencing.

Next-generation sequencing (NGS) has been implemented in clinical oncology to analyze multiple genes and to guide therapy. In patients with advanced lung cancer, small biopsies such as computed tomography-guided needle biopsy (CTNB), endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and transbronchial biopsy (TBB) are less invasive and are preferable to resection to make a pathological diagnosis. However, the quality of DNA/RNA and NGS from small lung tumor biopsy samples is unknown. Between April 2017 and March 2018, 107 consecutive samples were obtained from thoracic tumors or metastatic sites for targeted NGS analysis. Fifteen samples were obtained through CTNB, 11 through EBUS-TBNA, 11 through TBB and 70 through surgical resection. All samples were formalin-fixed and paraffin-embedded. DNA and RNA quality was measured using the ddCq method and the percentage of RNA fragments above 200 nucleotides (DV200), respectively. Our custommade probes were designed to capture exon sequences of 464 cancer-related genes and transcripts of 463 genes. DNA and RNA yield from the 3 biopsy methods were similar, and less than the yield obtained from resected samples. The quality of DNA and RNA was similar across all methods. Overall, 12 of 15 CTNB samples (80%), all 11 EBUS-TBNA samples, and 9 of 11 TBB samples (82%) underwent successful NGS assays from DNA. NGS analysis from RNA was successful in all 12 CTNB samples, 9 of 11 EBUS-TBNA samples (82%), and 8 of 11 TBB samples (73%). CTNB, EBUS-TBNA and TBB mostly resulted in adequate DNA and RNA quality and enabled high-quality targeted NGS analysis.

[Reexpansion Pulmonary Edema and Atrial Fibrillation after Resection of a Giant Solitary Fibrous Tumor of the Pleura].

We report a case of giant solitary fibrous tumor( SFT) of the pleura postoperatively complicated with probable reexpansion pulmonary edema and atrial fibrillation. An 85-year-old woman was diagnosed to have a 13 cm sized intrathoracic neoplasm. Upon thoracotomy, the tumor was found to pedunculate from the right lung with no direct invasion to the surrounding structures. Complete resection of the tumor and expansion of the right lung was obtained. Histopathology revealed the tumor was a benign SFT arising from the visceral pleura. An infiltrative shadow in the right lower lung field soon after the surgery suggested a reexpansion pulmonary edema, which eventually recovered within a week. The patient suffered from a refractory atrial fibrillation that led to a congestive heart failure requiring an intensive medical treatment. It is emphasized that thoracic surgeons should be aware of these postoperative complications in treating such a case like this.

Prognostic significance of the preoperative neutrophil-to-lymphocyte ratio for complete resection of thymoma.

PURPOSE: The preoperative peripheral neutrophil-to-lymphocyte ratio (NLR) is associated with a poor prognosis for various cancers. We evaluated the prognostic role of the preoperative NLR in patients with thymoma. METHODS: We reviewed the medical records of 254 patients who underwent resection of thymic epithelial tumors at our institution. Patients were excluded if they had received steroid therapy, neoadjuvant therapy, or incomplete resection, or if they had thymic carcinoma or Good's syndrome, recurrence of thymoma, or missing data. The NLR was measured preoperatively, and outcomes of patients with a low (< 1.96) vs those with a high (≥ 1.96) NLR were compared statistically. RESULTS: Of 159 eligible patients, 59 (37.1%) had a high NLR and 100 (62.9%) had a low NLR. Overall survival (OS), recurrence-free survival (RFS), disease-specific survival (DSS), disease-related survival (DRS), and the cumulative incidence of recurrence (CIR) differed significantly between the groups. Multivariate analyses revealed that a high NLR was independently associated with disease-related survival and a cumulative incidence of recurrence. A high NLR was also associated with a higher risk of recurrence of Masaoka stage I or II thymoma. CONCLUSIONS: An elevated preoperative NLR was associated with poor outcomes after thymoma resection. Thus, the NLR may be a useful biomarker of the postoperative prognosis of thymoma.

Prediction and prioritization of neoantigens: integration of RNA sequencing data with whole-exome sequencing.

The importance of neoantigens for cancer immunity is now well-acknowledged. However, there are diverse strategies for predicting and prioritizing candidate neoantigens, and thus reported neoantigen loads vary a great deal. To clarify this issue, we compared the numbers of neoantigen candidates predicted by four currently utilized strategies. Whole-exome sequencing and RNA sequencing (RNA-Seq) of four non-small-cell lung cancer patients was carried out. We identified 361 somatic missense mutations from which 224 candidate neoantigens were predicted using MHC class I binding affinity prediction software (strategy I). Of these, 207 exceeded the set threshold of gene expression (fragments per kilobase of transcript per million fragments mapped ≥1), resulting in 124 candidate neoantigens (strategy II). To verify mutant mRNA expression, sequencing of amplicons from tumor cDNA including each mutation was undertaken; 204 of the 207 mutations were successfully sequenced, yielding 121 mutant mRNA sequences, resulting in 75 candidate neoantigens (strategy III). Sequence information was extracted from RNA-Seq to confirm the presence of mutated mRNA. Variant allele frequencies ≥0.04 in RNA-Seq were found for 117 of the 207 mutations and regarded as expressed in the tumor, and finally, 72 candidate neoantigens were predicted (strategy IV). Without additional amplicon sequencing of cDNA, strategy IV was comparable to strategy III. We therefore propose strategy IV as a practical and appropriate strategy to predict candidate neoantigens fully utilizing currently available information. It is of note that different neoantigen loads were deduced from the same tumors depending on the strategies applied.

A deep azygoesophageal recess may increase the risk of secondary spontaneous pneumothorax.

PURPOSE: The azygoesophageal recess (AER) is known as a possible cause of bulla formation in patients with spontaneous pneumothorax. However, there has been little focus on the depth of the AER. We evaluated the relationship between the depth of the AER and pneumothorax development. METHODS: We conducted a retrospective study of 80 spontaneous pneumothorax patients who underwent surgery at our institution. We evaluated the depth of the AER on preoperative computed tomography scans. RESULTS: Ruptured bullae at the AER were found in 12 patients (52.2%) with secondary spontaneous pneumothorax (SSP) and 8 patients (14.0%) with primary spontaneous pneumothorax (PSP) (p < 0.001). In patients with ruptured bullae at the AER, 10 SSP patients (83.3%) had a deep AER while only 2 PSP patients (25%) had a deep AER (p = 0.015). CONCLUSIONS: A deep AER was more frequently associated with SSP than with PSP. A deep AER may contributes to bulla formation and rupture in SSP patients.

[Tracheal Resection and Reconstruction for a Squamous Cell Carcinoma of the Trachea;Report of a Case].

We report a case of tracheal resection and reconstruction for a squamous cell carcinoma of the trachea that was found in an 82-year-old male patient who had underwent right lower lobectomy for an adenosquamous cell carcinoma 3.5 years before. He noticed bloody sputum. Chest computed tomography (CT) revealed a 15 mm tumor in the anterior wall of the trachea. A transbronchial biopsy for the tracheal tumor showed a squamous cell carcinoma. Under right thoracotomy, we resected the tumor with 3 tracheal rings. Histologically a squamous cell carcinoma was diagnozed. As there was intraepithelial spread of cancer cells in the oral margin, the tracheal tumor was suspected to be a primary tracheal tumor rather than a metastasis from lung cancer. After the surgery, combination therapies of an external radiation therapy for 50 Gy and brachytherapy 2 times for totally 8 Gy were performed as a postoperative adjuvant therapy. He does not have any signs of recurrence in 1 year and 6 months after the surgery.

Outcomes of combined modality therapy for patients with stage III or IV mediastinal malignant germ cell tumors.

PURPOSE: The treatment of primary mediastinal germ cell tumors with cisplatin-based chemotherapy followed by surgery is an established practice; however, the prognosis has remained poor. This study reviews the survival outcomes of patients with primary mediastinal germ cell tumors to evaluate the efficacy of our treatment. METHODS: We retrospectively reviewed 11 consecutive patients with primary mediastinal germ cell tumors. RESULTS: We had treated four patients with seminomas and seven patients with non-seminomas. Ten patients had undergone cisplatin-based chemotherapy. All patients underwent complete resection. Two patients showed a failure of first-line chemotherapy and thus received salvage chemotherapies, including paclitaxel plus ifosfamide followed by high-dose carboplatin plus etoposide (TI-CE) with stem cell transplantation. One of them died of relapse 29 months later; while the other patient remained disease-free for 56 months postoperatively. The postoperative overall 3-year survival rates of the patients with non-seminomas and seminomas were 83 and 100%, respectively. CONCLUSION: Complete resection after establishing normalized or decreased at a low-level serum tumor markers plateau plays a crucial role in the management of patients with primary mediastinal malignant germ cell tumors.

[Paratracheal lymph node metastasis from papillary thyroid carcinoma presented as a middle mediastinal cyst;report of a case].

The majority of middle mediastinal cysts are benign diseases. However, some cases of middle mediastinal cysts are revealed to be malignant tumor. We herein report a case of a middle mediastinal cyst, which proved to be a right paratracheal lymph node metastasis from the thyroid papillary carcinoma. The patient was a 67-year-old lady who had underwent thyroidectomy and regional lymph node dissection for papillary thyroid carcinoma 6 years before. Follow-up computed tomography revealed a growing cyst at the right-side of the intrathoracic trachea. Metastasis from thyroid cancer was suspected from her history. The right upper mediastinal lymphadenectomy through thoracoscopy was performed. Pathologically, the cyst was diagnosed as a metastasis from thyroid cancer, showing cystic change.

Modified Ravitch procedure for pectus excavatum in Marfan syndrome with annuloaortic ectasia.

OBJECTIVES: This case series aimed to determine the feasibility of simultaneous modified Ravitch and David procedures for Marfan syndrome patients with pectus excavatum and annuloaortic ectasia. METHODS: Between March 2014 and December 2019, 7 consecutive patients underwent simultaneous surgery of modified Ravitch and David procedures for pectus excavatum and annuloaortic ectasia. The completion of cardiac surgery and sternal closure were followed by the modified Ravitch procedure. The bilateral fourth to seventh costal cartilages were resected, the sternal body partially wedge resected and the sternum raised anteriorly with re-suture. An oblique incision was performed on bilateral third costal cartilages, and they were fixed on top of each other, with the medial end superior and the lateral end inferior. The sternum was raised anteriorly, bypassing the fourth to seventh rib ends through the back of the sternum with threads. The feasibility and safety of the procedure were assessed through a retrospective review of the patients' clinical charts. RESULTS: The total sample had a median age of 28 years and comprised 5 males and 2 females. There was a significant difference in the preoperative and postoperative median Haller index, which were 6.8 and 3.9, respectively. All patients were discharged without serious complications, and there was no significant recurrence of pectus excavatum at 35-92 months postoperatively. CONCLUSIONS: The results of our case series suggest the feasibility of one-stage surgery for pectus excavatum combined with cardiac surgery using the modified Ravitch procedure. Future efforts should be tailored for more uneventful postoperative clinical courses.

Basiliximab for early perioperative transplant-associated thrombotic microangiopathy after lung transplantation: a case report.

BACKGROUND: Thrombotic microangiopathy is a syndrome characterized by microangiopathic hemolytic anemia and platelet aggregation, which is caused by endothelial injury, microcirculation thrombosis, and fibrin deposition. Transplant-associated thrombotic microangiopathy rarely occurs after lung transplantation and the onset is generally later than that after bone marrow or other solid organ transplantation. The treatment is to stop administration of the causal agent, which is often a calcineurin inhibitor, such as tacrolimus and cyclosporine. We herein report the case of a patient with early post-transplant thrombotic microangiopathy after lung transplantation treated by introducing basiliximab and temporarily stopping any calcineurin inhibitors until resuming treatment with an alternative calcineurin inhibitor. CASE PRESENTATION: A 58-year-old Asian woman underwent bilateral lung transplantation for hypersensitivity pneumonitis caused by an avian antigen, or bird fancier's lung disease. Postoperatively, she was started on triple immunosuppressive therapy, which included tacrolimus, mycophenolate mofetil, and steroids. On postoperative day 6, she developed thrombocytopenia followed by fever, hemolytic anemia, renal dysfunction, and purpura on her limbs and abdomen. She was diagnosed with transplant-associated thrombotic microangiopathy, and tacrolimus was thought to be the causal agent. We stopped tacrolimus and administered basiliximab. Then, she developed oliguria and needed continuous hemodiafiltration. On postoperative day 14, the platelet count recovered and she was switched from basiliximab to cyclosporine. Using this protocol, worsening thrombotic microangiopathy and acute rejection were avoided. CONCLUSIONS: We report the case of a patient with early post-transplant thrombotic microangiopathy after lung transplantation that was treated with basiliximab. Switching from calcineurin inhibitors using basiliximab may be an option for treating thrombotic microangiopathy without increasing the risk of acute rejection.

Respiratory strength and pectoralis muscle mass as measures of sarcopenia: Relation to outcomes in resected non-small cell lung cancer.

OBJECTIVES: Physical biomarkers to stratify patients with lung cancer into subtypes predictive of outcome beyond tumor-related characteristics are underexplored. This study was designed to investigate the clinical utility of preoperative sarcopenia based on respiratory strength and pectoralis muscle mass to predict the risk of death. METHODS: This retrospective study included 346 consecutive patients undergoing curative-intent resection of non-small cell lung cancer from 2009 to 2013. Respiratory strength and muscle mass were assessed by peak expiratory flow rate and pectoralis muscle index (pectoralis muscle area/body mass index) using preoperative spirometry and chest axial images, respectively. Sarcopenia cutoff points were defined by gender-specific medians of peak expiratory flow rates and pectoralis muscle indices. Survival was compared between patients with sarcopenia and patients without. RESULTS: Sarcopenia was present in 98 patients (28.3%) and was significantly associated with advancing age (P < .001). Patients with sarcopenia exhibited worse 5-year overall survival compared with patients without sarcopenia (69.9% vs 87.2%, P < .001). Multivariate analysis revealed that sarcopenia was an independent adverse prognostic factor (hazard ratio, 1.88; 95% confidence interval, 1.09-3.24; P = .023) after adjustment for gender, age, smoking status, coronary heart disease, diffusing capacity for carbon monoxide, neutrophil-to-lymphocyte ratio, albumin, histologic type, and pathologic stage. CONCLUSIONS: Preoperative sarcopenia as identified by the criteria of low respiratory strength and reduced pectoralis muscle mass is significantly associated with poor overall survival. This may help to develop more individualized management strategies and optimize longitudinal care for patients.

Composite Clonal Analysis Reveals Transition of NSCLC Subtypes Through Accumulation of Gene Mutations: A Case Report.

We analyzed an EGFR-mutated lung cancer with a pathologic diagnosis of combined large cell neuroendocrine carcinoma with mixed adenocarcinoma subtypes. Targeted next-generation sequencing of each component suggested that mutations in RB1, TP53, and SMAD4 and apparent loss of heterozygosity of TP53 and SMAD4 accompanied the transition of different adenocarcinoma subtypes. Additional gene mutations including PTEN, MST1R, and PIK3CA were noted during transdifferentiation from acinar adenocarcinoma to large cell neuroendocrine carcinoma. Combined DNA and RNA analysis using Todai OncoPanel revealed that transdifferentiation to different pathologic subtypes occurred in a single tumor through the accumulation of gene mutations.

Simultaneous single lobar lung transplantation and contralateral lung volume reduction.

Lung transplantation (LTx) and lung volume reduction surgery are established therapies for end-stage chronic obstructive pulmonary disease. Although native lung hyperinflation is a well-known complication of unilateral LTx for chronic obstructive pulmonary disease, the unilateral procedure continues to be performed because of severe shortages of cadaveric donors. As native lung hyperinflation can adversely affect the graft, all possible protection should be provided for patients with one-lobe transplantation. We report an emphysematous juvenile patient who successfully underwent simultaneous living-donor, single-lobe LTx and volume reduction in the contralateral lung.

Transplantation of Bioengineered Lungs Created From Recipient-Derived Cells Into a Large Animal Model.

The use of bioartificial lungs may represent a breakthrough for the treatment of end-stage lung disease. The present study aimed to evaluate the feasibility of transplanting bioengineered lungs created from autologous cells. Porcine decellularized lung scaffolds were seeded with porcine recipient-derived airway and vascular cells. The porcine recipient-derived cells were collected from lung tissue obtained by pulmonary wedge resection. Following culture of autologous cells in the scaffolds, the resulting grafts were unilaterally transplanted into porcine recipients (n = 3). Allograft left unilateral lung transplantation was performed in the control group (n = 3). Left unilateral transplantation of decellularized grafts was also performed in a separate control group (n = 2). In vivo functions were assessed for 2 hours after transplantation. Histologic evaluation and immunostaining showed the presence of airway and vascular cells in the bioengineered lungs. No animals survived in the decellularized transplant group, whereas all animals survived in the bioengineered transplant and allotransplant groups. However, bioengineered lung grafts showed marked bullous changes. The oxygen exchange was comparable between the bioengineered lung graft transplant and allograft transplant groups. However, the carbon dioxide gas exchange of the bioengineered lung graft transplant group was significantly lower than that of the allograft transplant group at 2 hours after transplantation (4.10 ± 0.87 mm Hg vs 24.7 ± 10.1 mm Hg, P = 0.02). Transplantation of bioartificial lung grafts created from autologous cells was feasible in the super-acute phase. However, bullous changes and poor carbon dioxide gas exchange remain limitations of this method.

Preoperative lung surface localization for pulmonary wedge resection: a single-center experience.

BACKGROUND: Preoperative lung surface localization is effective in sublobar resection for small lung nodules. However, the efficacy may vary depending on the underlying conditions of the lung and tumor, as well as the technique. This study aimed to evaluate the efficacy and limitations of preoperative lung surface localization for wedge resection by analyzing the outcomes of computed tomography (CT)-guided percutaneous marking and virtual-assisted lung mapping (VAL-MAP). METHODS: We investigated 215 patients who underwent curative wedge resection for malignant tumors using CT-guided localization or VAL-MAP from 1998 to 2018 in our institute. Each resected nodule was assessed for successful resection, which was defined as complete resection with adequate margins. RESULTS: One-hundred-and-nineteen patients with 153 nodules were included. The overall successful resection rate was 87.6%. The successful resection rate was significantly lower for nodules with intraoperative adhesion than those without intraoperative adhesion (75.0% vs. 90.1%; P=0.034), and for tumors requiring deep resection margins (>31 mm) than those requiring shallow margins (≤31 mm) (76.7% vs. 94.6%; P=0.002). Although the successful resection rate for nodules resected using CT-guided localization was significantly lower in cases with versus without intraoperative adhesion (54.5% vs. 86.7%; P=0.048), the successful resection rate for nodules resected using VAL-MAP was not influenced by the presence or absence of adhesion (85.7% vs. 93.4%; P=0.491). CONCLUSIONS: A requirement for deeper resection and the presence of intraoperative adhesion were limitations of preoperative lung surface localization for curative pulmonary wedge resection.

Prognostic significance of low pectoralis muscle mass on preoperative chest computed tomography in localized non-small cell lung cancer after curative-intent surgery.

OBJECTIVES: The impact of sarcopenia on the outcome in patients following resection of non-small cell lung cancer is yet to be fully determined. This study aimed to evaluate the clinical utility of a computed tomography-based pectoralis muscle assessment, which reflects sarcopenia, to predict the risk of postoperative outcomes. MATERIALS AND METHODS: This retrospective study included 347 consecutive patients undergoing curative-intent resection of non-small cell lung cancer from 2009 to 2013. The pectoralis muscle index (pectoralis muscle area/body mass index) was assessed at the level of the fourth thoracic vertebra on chest axial images. The primary outcomes were compared between the lowest gender-specific quintile (sarcopenia) and the other quintiles according to the index. The prognostic significance of low pectoralis muscle index was calculated by the Cox proportional hazards regression model. A propensity score matching analysis was performed to adjust the differences in clinical characteristics. RESULTS: Sixty-nine patients were identified with sarcopenia according to the lowest gender-specific quintile of pectoralis muscle index. Patients with sarcopenia exhibited worse 5-year overall survival rate compared with patients without sarcopenia (64.2 % vs. 86.7 %, P < 0.001). Even in stage I non-small cell lung cancer, the rate of 5-year overall survival in the sarcopenia group was lower than that in the non-sarcopenia group (74.2 % vs. 92.4 %, P = 0.001). Multivariate analysis revealed that low pectoralis muscle index was independently associated with adverse overall survival (hazard ratio: 2.09, 95 % confidence interval: 1.20-3.62, P = 0.009). After propensity score matching, the prognostic impact of sarcopenia based on low pectoralis muscle index was also robust for overall survival (hazard ratio: 3.23, 95 % confidence interval: 1.38-7.60, P = 0.007). CONCLUSIONS: Low pectoralis muscle index was significantly associated with poor long-term outcomes in patients with localized non-small cell lung cancer after curative surgery. This may help assist preoperative risk stratification and longitudinal management after surgery.

ɤ-glutamyl hydroxymethyl rhodamine green fluorescence as a prognostic indicator for lung cancer.

OBJECTIVE: ɤ-glutamyltranspeptidase is an enzyme expressed in various malignancies including lung cancer. It rapidly activates non-fluorescent ɤ-glutamyl hydroxymethyl rhodamine green to highly fluorescent hydroxymethyl rhodamine green. The resultant tumor fluorescence is therefore an indicator of cellular ɤ-glutamyltranspeptidase activity. We have explored the use of ɤ-glutamyl hydroxymethyl rhodamine green as an intraoperative imaging tool for visualizing cancers. Herein, we evaluated the potential of the tumor fluorescence as a postoperative prognostic indicator. METHODS: We included patients with non-small cell lung cancer who had undergone radical resection from 2012 to 2014 in the study. We assessed the fluorescence intensity of the resected tumor and normal lung tissue by ex vivo imaging using ɤ-glutamyl hydroxymethyl rhodamine green. RESULTS: Sixty-seven patients were eligible for the study (adenocarcinomas, n = 44; squamous cell carcinoma, n = 14; other histologies, n = 8). The pathological stages were I, II, III, and IV in 39, 15, 12, and 1 patient, respectively. Based on the fluorescence of the tumor tissue, the patients were divided into high fluorescence (n = 33) and low fluorescence (n = 34) groups. The 5-year overall survival rate was significantly higher in the high fluorescence group (72.7%) compared to the low fluorescence group (47.1%, P = 0.025). Similarly, pathological stage I patients of the high fluorescence group had higher 5-year overall survival (85.7% vs. 44.4%, P = 0.009) and recurrence-free survival (76.2% vs. 44.4% P = 0.044) rates compared to those of the low fluorescence group. CONCLUSIONS: ɤ-glutamyl hydroxymethyl rhodamine green fluorescence is a good postoperative prognostic indicator in patients with non-small cell lung cancer.

Clinical Application of Next-generation Sequencing for the Diagnosis of Lung Squamous Cell Carcinoma: Is It Primary or Secondary?

An 80-year-old man with a history of cutaneous squamous cell carcinoma (SCC) was referred to our department for a solitary lung nodule. The nodule was surgically resected and diagnosed as SCC. Because the lung lesion and a previous skin lesion showed similar histological findings, the origin of the lung tumor was uncertain. Next-generation sequencing using a targeted driver oncogene panel was applied for the further examination. The lung lesion was diagnosed as primary lung SCC, as the two tumors possessed distinct somatic mutations in TP53. Recent advances in clinical sequencing have enabled us to obtain an accurate diagnosis in pathologically challenging cases.

Adoptive transfer of zoledronate-expanded autologous Vγ9Vδ2 T-cells in patients with treatment-refractory non-small-cell lung cancer: a multicenter, open-label, single-arm, phase 2 study.

BACKGROUND: Not all non-small cell lung cancer (NSCLC) patients possess drug-targetable driver mutations, and response rates to immune checkpoint blockade therapies also remain unsatisfactory. Therefore, more effective treatments are still needed. Here, we report the results of a phase 2 clinical trial of adoptive cell therapy using zoledronate-expanded autologous Vγ9Vδ2 T-cells for treatment-refractory NSCLC. METHODS: NSCLC patients who had undergone at least two regimens of standard chemotherapy for unresectable disease or had had at least one treatment including chemotherapy or radiation for recurrent disease after surgery were enrolled in this open-label, single-arm, multicenter, phase 2 study. After preliminary testing of Vγ9Vδ2 T-cell proliferation, autologous peripheral blood mononuclear cells were cultured with zoledronate and IL-2 to expand the Vγ9Vδ2 T-cells. Cultured cells (>1×109) were intravenously administered every 2 weeks for six injections. The primary endpoint of this study was progression-free survival (PFS), and secondary endpoints included overall survival (OS), best objective response rate (ORR), disease control rate (DCR), safety and immunomonitoring. Clinical efficacy was defined as median PFS significantly >4 months. RESULTS: Twenty-five patients (20 adenocarcinoma, 4 squamous cell carcinoma and 1 large cell carcinoma) were enrolled. Autologous Vγ9Vδ2 T-cell therapy was administered to all 25 patients, of which 16 completed the foreseen course of 6 injections of cultured cells. Median PFS was 95.0 days (95% CI 73.0 to 132.0 days); median OS was 418.0 days (179.0-479.0 days), and best overall responses were 1 partial response, 16 stable disease (SD) and 8 progressive disease. ORR and DCR were 4.0% (0.1%-20.4%) and 68.0% (46.5%-85.1%), respectively. Severe adverse events developed in nine patients, mostly associated with disease progression. In one patient, pneumonitis and inflammatory responses resulted from Vγ9Vδ2 T-cell infusions, together with the disappearance of a massive tumor. CONCLUSIONS: Although autologous Vγ9Vδ2 T-cell therapy was well tolerated and may have an acceptable DCR, this trial did not meet its primary efficacy endpoint. TRIAL REGISTRATION NUMBER: UMIN000006128.

Virtual-Assisted Lung Mapping 2.0: Preoperative Bronchoscopic Three-Dimensional Lung Mapping.

PURPOSE: To better determine suitable resection lines for sublobar lung resection, especially to obtain sufficient resection depth, a novel technique of virtual-assisted lung mapping (VAL-MAP) 2.0 was developed by combining multispot dye marks (conventional VAL-MAP) and a deeply placed microcoil. DESCRIPTION: With the patient under local anesthesia and sedation, multiple dye marks were bronchoscopically made on the lung surface. Microcoils were then bronchoscopically placed centrally to the tumor to indicate deep resection margins. Postmapping computed tomography confirmed the marking locations. EVALUATION: Six patients underwent VAL-MAP 2.0: 5 for wedge resection and 1 for segmentectomy. The mean diameter and depth of the targeted lesions were 10.0 ± 4.1 and 12.6 ± 10.3 mm, respectively. In total, 18 dye marks and 9 microcoils were placed without major complications. The microcoils were successfully identified with intraoperative fluoroscopy, effectively assisting the surgeons' decision regarding the deep resection lines. CONCLUSIONS: This study confirmed the safety and feasibility of VAL-MAP 2.0. This technique effectively assisted surgeons to obtain sufficient resection margins in sublobar lung resection, even when removing deeply located lesions.