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The phase 3 RATIONALE-303 trial (NCT03358875) investigated the efficacy and safety of tislelizumab versus docetaxel in pretreated patients with advanced NSCLC. Here, we report the efficacy and safety results and describe the exploratory biomarker analyses.A total of 805 patients aged more than or equal to 18 years with locally advanced or metastatic squamous or nonsquamous NSCLC were randomized 2:1 to intravenous tislelizumab 200 mg or docetaxel 75 mg/mAt the prespecified interim analysis (August 10, 2020), the co-primary end point of OS in the ITT population was met, with a statistically significant and clinically meaningful improvement in OS with tislelizumab versus docetaxel (median 17.2 versus 11.9 mo, respectively; hazard ratio [HR] = 0.64, p0.0001). At the final analysis (July 15, 2021), the other co-primary end point of OS in the PD-L1 tumor cell greater than or equal to 25% population was further met (median 19.3 versus 11.5 mo, respectively; HR = 0.53, p0.0001), and OS continued to improve in the ITT population (median 16.9 versus 11.9 mo, respectively, HR = 0.66). Exploratory biomarker analyses revealed the potential association of NOTCH1-4 mutations with improved tislelizumab efficacy for both OS and progression-free survival, whereas tissue tumor mutation burden correlated with progression-free survival benefit, but not OS benefit. No new safety signals were identified.Tislelizumab was found to have a significantly improved and long-term clinical benefit in OS versus docetaxel in pretreated patients with advanced NSCLC, regardless of PD-L1 expression.

Clinical cases of uterine leiomyoma with secondary lung involvement are described. The results of X-ray, computerized tomography, and histological examination of lung specimens, as well as those of heterozygosity and microsatellite instability are presented. Our own experience and the few descriptions available to date in the literature confirm the pseudo tumorous nature of benign uterine leiomyoma with lung involvement which should be considered as nodular dyshormonal hyperplasia. The signs of genetic instability ՛s identification do not allow to differentiate clearly between the benign or malignant nature of the disease. The key role in the differential diagnosis of uterine leiomyoma with lung involvement and leiomyosarcoma belongs to unprejudiced clinical observation.

Surgical biopsy – an invasive procedure that may be accompanied by an increased risk of complications and lethality is required in approximately ⅓ cases when diagnosing interstitial lung diseases (ILD). The article summarizes the experience of using surgical diagnostic methods in patients with ILD. Methods . A retrospective analysis of the medical records of patients ( n = 104: 61 (59%) men, 43 (41%) women; at the age of 20–78 years) who were operated on for ILD for histological verification of the disease was carried out. The method of choice was video-assisted thoracic edge resection of the lung (VATER). If there are contraindications to VATER, thoracotomy was performed. Patients with spontaneous pneumothorax (SP) episodes had an anamnesis of costal pleuralectomy in order to prevent recurrence. Results . According to the examination data, the average rate of forced expiratory volume in the 1 st second during the preoperative examination was 73.8%, lung diffusion capacity – 63.2% VATER was performed for 99 (95%) patients, OPD – 4 (4%), access conversion – 1 (1%). In 10 (10 %) cases in the anamnesis or at admission is noted by SP. Postoperative complications were observed in 5 (5%) cases. All complications are eliminated without invasive procedures. There were no lethal outcomes. Conclusion . In 94% of cases of ILD, an accurate diagnosis was made using surgical methods, which was significantly reflected in the development of treatment tactics in 82 (79%) patients and allowed for effective anti-relapsing treatment in case of complication of the main disease – SP. This fact testifies to the high diagnostic significance of surgical methods in patients with ILD, and the low level of complications – about their relative safety in properly selected patients.

The analysis of literature on the possibility of performing anatomical pulmonary resections in patients with concomitant COPD was performed. According to most researchers, FEV1 and DL (CO) more than 80 % indicated a high probability of an uncomplicated postoperative period after any anatomical resection of the lung. If the specified parameters were less than 80 %, additional studies were required: functional tests (6-minute walk test, staircase test), stress testing, calculation of predicted postoperative values of respiratory function, and, if necessary, lung scintigraphy could be performed to study regional respiratory function. The decision about the possibility and need for surgical treatment should have been made individually at the threshold values of these parameters. At the same time, there is currently no system for assessing the risk of postoperative complications for a particular patient, based on all the information about it, which represents the potential for further research.The authors declare no conflict of interest.The authors confirm that they respect the rights of the people participated in the study, including obtaining informed consent when it is necessary, and the rules of treatment of animals when they are used in the study. Author Guidelines contains the detailed information.

Background Visualization of Indocyanine Green (ICG) near-infrared (NIR) fluorescence is a promising technique for biomedical applications because of its deep tissue penetration, low autofluorescence, weak dependence on ambient light, safety for patients and medical staff. Methods To apply this technique to animal studies and clinical practice, we developed multispectral NIR fluorescence imaging system FLUM-808, which can be used in experimental studies and clinical practice, in open and endoscopic surgery (fluorescence-guided surgery). The object is illuminated either directly or through an illumination channel depending on what optical instrument is used (camera lens, fiber endoscope, rigid endoscope, surgical microscope, etc.). The system is able to simultaneously display NIR images and images captured under white light. Results This article provides examples of imaging techniques used during open and endoscopic surgery with ICG as an NIR fluorescent dye and photosensitizer, demonstrates applications of the technique for experimental and clinical purposes: for intraoperative imaging of blood and lymphatic vessels; for detection of tumors and sentinel lymph nodes; for assessment of tissue, organ, or anastomotic blood supply. Conclusions This method significantly helps to accurately assign the areas of increased fluorescence to certain anatomical structures during surgery. NIR fluorescence diagnosis can be used in important experimental studies and in clinical practice. The described results of ICG studies can help in developing new fluorescence-based diagnostic and theranostic approaches employing more effective exogenous fluorophores and photosensitizers.

Background Novel adjuvant strategies are needed to optimise outcomes after complete surgical resection in patients with early-stage non-small-cell lung cancer (NSCLC). We aimed to evaluate adjuvant atezolizumab versus best supportive care after adjuvant platinum-based chemotherapy in these patients. Methods IMpower010 was a randomised, multicentre, open-label, phase 3 study done at 227 sites in 22 countries and regions. Eligible patients were 18 years or older with completely resected stage IB (tumours ≥4 cm) to IIIA NSCLC per the Union Internationale Contre le Cancer and American Joint Committee on Cancer staging system (7th edition). Patients were randomly assigned (1:1) by a permuted-block method (block size of four) to receive adjuvant atezolizumab (1200 mg every 21 days; for 16 cycles or 1 year) or best supportive care (observation and regular scans for disease recurrence) after adjuvant platinum-based chemotherapy (one to four cycles). The primary endpoint, investigator-assessed disease-free survival, was tested hierarchically first in the stage II-IIIA population subgroup whose tumours expressed PD-L1 on 1% or more of tumour cells (SP263), then all patients in the stage II-IIIA population, and finally the intention-to-treat (ITT) population (stage IB-IIIA). Safety was evaluated in all patients who were randomly assigned and received atezolizumab or best supportive care. IMpower010 is registered with ClinicalTrials.gov, NCT02486718 (active, not recruiting). Findings Between Oct 7, 2015, and Sept 19, 2018, 1280 patients were enrolled after complete resection. 1269 received adjuvant chemotherapy, of whom 1005 patients were eligible for randomisation to atezolizumab (n=507) or best supportive care (n=498); 495 in each group received treatment. After a median follow-up of 32·2 months (IQR 27·4-38·3) in the stage II-IIIA population, atezolizumab treatment improved disease-free survival compared with best supportive care in patients in the stage II-IIIA population whose tumours expressed PD-L1 on 1% or more of tumour cells (HR 0·66; 95% CI 0·50-0·88; p=0·0039) and in all patients in the stage II-IIIA population (0·79; 0·64-0·96; p=0·020). In the ITT population, HR for disease-free survival was 0·81 (0·67-0·99; p=0·040). Atezolizumab-related grade 3 and 4 adverse events occurred in 53 (11%) of 495 patients and grade 5 events in four patients (1%). Interpretation IMpower010 showed a disease-free survival benefit with atezolizumab versus best supportive care after adjuvant chemotherapy in patients with resected stage II-IIIA NSCLC, with pronounced benefit in the subgroup whose tumours expressed PD-L1 on 1% or more of tumour cells, and no new safety signals. Atezolizumab after adjuvant chemotherapy offers a promising treatment option for patients with resected early-stage NSCLC. Funding F Hoffmann-La Roche and Genentech.

Background Cosibelimab is a high affinity, fully-human IgG1 monoclonal antibody that directly binds to programmed death ligand-1 (PD-L1) and blocks its interaction with the programmed death receptor-1 (PD-1) and B7.1 receptors to restore an anti-tumor immune response. Cosibelimab has the additional benefit of a functional Fc domain capable of inducing antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity against tumor cells. Study CK-301–101 is a global, multicenter, multicohort trial that is enrolling patients (pts) with select advanced cancers, including pivotal cohorts of pts with metastatic and locally advanced cutaneous squamous cell carcinoma (cSCC) and a cohort of pts with previously untreated advanced non-small cell lung cancer (NSCLC). Methods Eligible pts were aged ≥18 years with an Eastern Cooperative Oncology Group performance status of 0–1. The cSCC cohorts enrolled pts with histologically confirmed metastatic or locally advanced cSCC not amenable to local therapy. The NSCLC cohort enrolled previously untreated NSCLC pts with advanced disease and a PD-L1 tumor proportion score of at least 50%. Pts received a fixed dose of 800 mg cosibelimab administered intravenously every two weeks. Anti-tumor activity was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and were conducted every 8 weeks for the initial 32 weeks on study, and every 12 weeks thereafter. Results As of August 2020, 114 pts (73M/41F, median age 66 years) with diverse tumor types have been enrolled and treated with cosibelimab. Among these pts, 103 (90%) experienced ≥1 treatment-emergent adverse event (AE), 42 (37%) experienced a grade ≥3 AE, and 6 (5%) experienced a grade ≥3 drug-related AE. The most common AEs were fatigue (25%), anemia (21%), rash (18%) and nausea (16%) and the most common drug-related AEs were fatigue (15%) and rash (14%). In 42 cSCC pts evaluable for response, ORR based on investigator assessment of tumor response was 55% (95% confidence interval [CI]: 39, 70), including 5 (12%) complete responses, with 20/23 (87%) responses ongoing and 10 responses ≥6 months in duration as of data cutoff. In 25 NSCLC pts evaluable for response, ORR based on investigator assessment was 44% (95% CI: 24, 65), with 5/11 (45%) responses ongoing and 10 responses ≥6 months in duration. Conclusions Cosibelimab has a predictable and manageable safety profile and demonstrated robust clinical activity in cSCC and NSCLC pts, including durable complete and partial responses. Updated results will be presented. Trial Registration NCT03212404 Ethics Approval The study was approved by an appropriate ethics committee for each participating institution. Informed consent was obtained for all subjects. Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

To develop a method for analysis of lymphatic drainage pathways from the lobe of the lung affected by non-small cell lung cancer (NSCLC) using infrared fluorescence.A study enrolled patients with NSCLC who underwent anatomic resection of the lung with systematic lymph node dissection and preliminary intraoperative peritumoral injection of indocyanine green conjugate with human albumin. Registration of fluorescence in regional lymph nodes (LN) was carried out immediately after excision of specimen using the FLUM-808 instrumental system.Infrared fluorescence was observed in 117 hilar and mediastinal lymph nodes from 43 patients (2.7 nodes per a patient). Comparison of localization of fluorescent LN with localization of tumor in various lobes established significant variability of lymphatic drainage pathways.The developed method of infrared fluorescent evaluation of lymphatic drainage in patients with NSCLC confirms the necessity of systematic lymph node dissection for adequate staging.Цель исследования - разработка метода изучения лимфооттока от пораженной немелкоклеточным раком доли легкого методом инфракрасной флуоресценции. Материал и методы. В исследование включены больные немелкоклеточным раком легкого, перенесшие анатомическую резекцию легкого с систематической лимфодиссекцией и предварительным интраоперационным перитуморальным введением конъюгата индоцианина зеленого с альбумином человека. Регистрацию флуоресценции в регионарных лимфатических узлах проводили сразу после удаления препарата при помощи инструментальной системы FLUM-808. Результаты. Инфракрасная флуоресценция зафиксирована у 43 пациентов в 117 лимфатических узлах корня легкого и средостения (в среднем - 2,7 лимфатических узла у 1 больного). Сопоставление локализации флуоресцирующих лимфатических узлов с локализацией опухоли в той или иной доле легкого установило существенную вариабельность лимфооттока. Заключение. Результаты, полученные с помощью разработанного метода инфракрасного флуоресцентного изучения лимфооттока у больных немелкоклеточным раком легкого, подтверждают необходимость выполнения систематической лимфодиссекции с целью адекватного стадирования.

Recurrent respiratory papillomatosis (RRP) is a rare disease caused by human papillomavirus. Aggressive forms of RRP require repeated cytoreductive surgery to restore airway patency. Tracheal disease is even less common and lung parenchyma is involved in less than 1% of patients. We present reports of three cases of RRP with progressive lung disease in adult patients. Keywords: Respiratory papillomatosis, Airways, Pulmonary parenchyma, Cavitation

Background: This study evaluated the distribution of epidermal growth factor receptor (EGFR) T790M mutations in treatment-naïve tumor and normal samples obtained from cancer patients. Methods: We utilized allele-specific PCR (AS-PCR), digital droplet PCR (ddPCR) and next generation sequencing (NGS) to detect EGFR T790M allele in several collections of tumor and normal human tissues. Results: AS-PCR analysis of treatment-naïve tumor samples revealed somatic T790M mutation in 3/394 (1%) non-small cell lung carcinomas (NSCLC) carrying the tyrosine kinase inhibitor (TKI)-sensitizing EGFR mutation, but in none of 334 NSCLC lacking EGFR exon 19 deletions (ex19del) or L858R substitutions and in none of 235 non-lung tumors. Use of highly sensitive and quantitative assays, such as ddPCR and NGS, produced a high number of T790M-specific signals even in presumably T790M-negative DNA specimens. This background noise was evidently higher in degraded DNA isolated from formalin-fixed paraffin-embedded tissues as compared to high molecular weight DNA. A combination of AS-PCR, ddPCR and NGS revealed mosaic EGFR T790M allele in 2/68 (3%) NSCLC treated with the first-generation TKI. Both these tumors produced evident and durable response to gefitinib. Conclusion: Detection of mosaic EGFR T790M mutation in treatment-naïve samples may be compromised by yet unresolved technical issues and may have limited clinical value.

The authors made a prospective randomized comparison of results of preoperative photodynamic therapy (PhT) with chemotherapy, preoperative chemotherapy in initial unresectable central non-small cell lung cancer in stage III. The efficiency and safety of preoperative therapy were estimated as well as the possibility of subsequent surgical treatment. The research included patients in stage IIIA and IIIB of central non-small cell lung cancer with lesions of primary bronchi and lower section of the trachea, which initially were unresectable, but potentially the patients could be operated on after preoperative treatment. The photodynamic therapy was performed using chlorine E6 and the light of wave length 662 nm. Since January 2008 till December 2011, 42 patients were included in the research, 21 patients were randomized in the group for photodynamic therapy and 21 — in group without PhT. These groups were compared according to their sex, age, stage of the disease and histological findings. After nonadjuvant treatment the remissions were reached in 19 (90%) patients of the group with PhT and in 16 (76%) patients without PhT and all the patients were operated on. The explorative operations were made on 3 patients out of 16 operated on in the group without PhT (19%). In the group PhT 14 pneumonectomies and 5 lobectomies were perfomed opposite 10 pneumonectomies and 3 lobectomies in group without PhT. The degree of radicalism of resection appears to be reliably higher in the group PhT (RO– 89%, R1–11% as against RO–54%, R1–46% in group without PhT), p=0,038. The preoperative endobronchial PhT conducted with chemotherapy was characterized by efficiency and safety, allowed the surgical treatment and elevated the degree of radicalism of this treatment in selected patients, initially assessed as unresectable.

Results From RATIONALE 303: A Global Phase 3 Study of Tislelizumab (TIS) vs Docetaxel (TAX) as Second- or Third-Line Therapy for Patients With Locally Advanced or Metastatic NSCLC Background: Anti-PD-1/L1 therapies have improved OS by 2-4 mo vs TAX in patients (pts) with advanced NSCLC who progressed after platinum regimens. TIS is an anti-PD-1 antibody engineered to minimize FcγR binding on macrophages, a mechanism of T-cell clearance and potential anti-PD-1 resistance. Methods: RATIONALE 303 (BGB-A317-303; NCT03358875) compared efficacy and safety of TIS vs TAX as 2 or 3L therapy for pts with advanced NSCLC. Patients without oncogenic driver mutation who failed at least 1 prior systemic therapy including a platinum regimen were randomized 2:1 to receive TIS 200 mg IV Q3W (Arm A) or TAX 75 mg/m2 IV Q3W (Arm B). Dual primary endpoints were OS in the ITT analysis set and OS in the PD-L1 high (≥25% TC) analysis set. A prespecified interim analysis (IA) was conducted after ≈426 deaths (76% of planned events); in the IA, formal OS superiority testing was conducted only in the ITT. The IA results are presented. Results: Overall, 805 pts were randomized (n=535, TIS; n=270, TAX); demographics were generally balanced between arms. With a 19-mo median follow-up (441 OS events), median OSITT was significantly longer in Arm A vs B (17.2 vs 11.9 mo; HR=0.64 [95% CI: 0.53, 0.78]; P Conclusions: RATIONALE 303 demonstrated that, as 2 or 3L therapy in pts with advanced NSCLC, TIS was tolerable and prolonged OS by 5-7 mo with improved PFS and ORR vs TAX regardless of histology or PD-L1 expression. ITT Analysis Set (N=805)Arm A Tislelizumab (n=535)Arm B Docetaxel (n=270)EfficacyMedian OS, mo17.211.9OS difference, mo5.3HR (95% CI)a0.64 (0.53, 0.78)P-valuea,b Citation Format: Caicun Zhou, Dingzhi Huang, Xinmin Yu, Yunpeng Liu, Yun Fan, Yongqian Shu, Zhiyong Ma, Ziping Wang, Ying Cheng, Jie Wang, Sheng Hu, Zhihua Liu, Mikhail Dvorkin, Elena Poddubskaya, Umut Disel, Andrey Akopov, Yiyuan Ma, Yan Wang, Zhenyu Pan, Cunjing Yu, Gareth Rivalland. Results from RATIONALE 303: A global phase 3 study of tislelizumab (TIS) vs docetaxel (TAX) as second- or third-line therapy for patients with locally advanced or metastatic NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT039.

OBJECTIVE. The research evaluated efficacy of combined treatment of initially nonresectable and inoperable cases of non-small cell lung cancer. The treatment consisted of preoperative endobronchial and intraoperave photodynamic therapies. MATERIAL AND METHODS. The prospective investigation included patients with central non-small cell lung cancer. These cases were initially considered as nonresectable (the trachea was involved in tumor) or inoperable (functional intolerance of pneumoectomy/ bilobectomy). Neoadjuvant chemotherapy (2-6 courses) and endobronchial photodynamic therapy (PDT) were conducted for these patients in preoperative period. PDT of resection edge was carried out during the operation and it was straight away after specimen removal and ipsilateral lymphodissection. RESULTS. The research was made on 38 patients. Lung resections underwent 30 (79 %) patients. Surgeries included 20 pneumoectomies and 10 lobectomies. Bronchial resection was performed by crossing an initially affected zone. It was noted that 5-year survival consisted of 68 %. CONCLUSIONS. Photodynamic therapy was important in combination with chemotherapy and surgical treatment of central non-small cell lung cancer. These measures allowed doctors to decrease the resection volume in part of inoperable patients or patients with initially nonresectable tumors.

Background Photodynamic therapy (PDT) has several advantages. However, one of the disadvantages is its inability to be individualized according to biological characteristics of malignant tumors. The objective of this study was to investigate a strategy for individualized endobronchial PDT in the treatment of centrally located non-small cell lung cancer. Methods New approach suggests taking fluorescence-based measurements of chlorine E6 photosensitizer (PS) accumulation in the malignant tumor tissue, and assess PS consumption rate during PDT. Two randomized groups of 45 patients took part in the comparative study of standard PDT procedure, 662 nm, pulse-periodic mode, therapeutic light (reference group – RG) versus the investigated individualized approach under fluorescence control after irradiation with violet light, 408 nm, diagnostic light (study group – SG). The PDT-treatment parameters and results of follow-up bronchoscopy were compared between the groups. Results 43 (96%) of 45 patients in SG demonstrated intense fluorescence in the area of the tracheal/bronchial tumor stenosis. 4 (9%) of 45 patients (SG) demonstrated fluorescence of mucosa areas distant from the main tumor lesion after violet light irradiation. Mean fluence during the whole PDT procedure was 95 ± 20 J/cm 2 (range 60–130 J/cm 2 ), which was significantly lower than in RG (p = 0.01). Total exposure time was significantly lower in SG (365 ± 65 s), compared with RG (690 ± 65 s), P = 0.001. According to the follow-up bronchoscopy the difference in the PDT-treatment results between the groups is statistically insignificant. Conclusions The investigated strategy suggests using fluorescence control of the efficacy of PDT-treatment (photodynamic theranostics) to optimize and individualize the PDT procedure.

OBJECTIVE. The research showed the possibility of operative treatment of patients with terminal stage of respiratory failure who underwent long-term oxygen therapy. MATERIAL AND METHODS. Surgical correction of respiratory failure was performed for two patients after clinical, functional and radio studies. RESULTS. The degree of arterial hypoxemia significantly decreased after operation due to improved ventilation of maximally saved pulmonary tissue areas. This allowed doctors to apply a situational oxygen therapy. Tolerance of physical activity reliably improved and value of BODE-index decreased. CONCLUSIONS. The terminal stage of respiratory failure couldn’t be a contraindication to surgical treatment.

The article describes an anesthetic management strategy for resection of the cervical trachea due to benign stenosis without using an endotracheal tube. The strategy includes: (1) insertion of an airway stent in the stenotic area, (2) insertion of a supraglottic airway device (SGAD), and (3) advancing a jet ventilation catheter through the SGAD. The stent is removed during surgery together with the resected part of the trachea. The technique of nonintubated tracheal resection allows the surgeon to work most comfortably and helps the anesthesiologist properly maintain the patient's vital functions in the operating room.

8500 Background: Adjuvant platinum-based chemotherapy (chemo) provides only a modest 5-year survival benefit in fully resected, high-risk early-stage NSCLC. We report the primary disease-free survival (DFS) results from the pre-planned interim analysis of IMpower010, a randomized phase 3 open-label trial of adjuvant atezolizumab (atezo; anti–PD-L1) vs best supportive care (BSC) after adjuvant chemo in patients (pts) with early-stage resected NSCLC. Methods: Eligible pts had completely resected (4-12 weeks prior to enrollment) Stage IB (≥4 cm)-IIIA NSCLC (AJCC/UICC v7) and ECOG PS 0-1. A total of 1280 pts were enrolled, and 1269 pts received up to four 21-day cycles of cisplatin-based chemo (plus pemetrexed, docetaxel, gemcitabine or vinorelbine). Of these pts (n=1269), 1005 were subsequently randomized 1:1 to 16 cycles of atezo 1200 mg Q3W or BSC. The primary endpoint of investigator-assessed DFS and secondary endpoint of overall survival (OS) were tested hierarchically: first DFS in the PD-L1 TC ≥1% (SP263) subgroup with Stage II-IIIA disease, then DFS in all randomized pts with Stage II-IIIA disease, then DFS in the ITT population (Stage IB-IIIA) and finally OS in the ITT population. Efficacy assessments were based on randomized pts. Safety was assessed in the safety-evaluable population, defined as pts who received ≥1 dose of atezo or who had ≥1 post-baseline safety assessment if randomized to the BSC arm. Results: At data cutoff (January 21, 2021), median follow-up was 32.2 months in the ITT population. Baseline characteristics were generally balanced between arms. Atezo showed statistically significant DFS benefit vs BSC in the PD-L1 TC ≥1% Stage II-IIIA and all randomized Stage II-IIIA populations; the significance boundary was not crossed for DFS in the ITT population (Table). OS data were immature and not formally tested. Pts in the atezo arm received a median of 16 (range, 1-16) atezo doses. Any-grade AEs occurred in 92.7% (atezo) and 70.7% (BSC); events were Grade 3/4 in 21.8% and 11.5%, respectively. Grade 5 treatment-related AEs occurred in 0.8% of pts in the atezo arm. AEs leading to atezo discontinuation occurred in 18.2% of atezo-treated pts. Conclusions: IMpower010 met its primary endpoint, showing DFS benefit with adjuvant atezo vs BSC after adjuvant chemo in pts with resected Stage II-IIIA NSCLC, with pronounced benefit in the PD-L1 TC ≥1% subgroup. The safety profile of atezo was consistent with prior experience of atezo monotherapy across indications and lines of therapy. Funding: F. Hoffmann-La Roche Ltd. Clinical trial information: NCT02486718. [Table: see text]

One of the disadvantages of photodynamic therapy is impossibility to specify the method according to biological features of malignant tumor such as a degree of blood supply, accumulation of photosensibilizator in tumorous tissue, proliferative activity and etc. The authors aimed to develop a mode of individualization of endobronchial photodynamic therapy of central non-small cell carcinoma of lung and assessment of method efficacy. The suggested method is based on fluorescent diagnostics of degree of accumulation of photosensibilizator in timorous tissue and the rate of its expenditure in process of performing of photodynamic therapy. There was made a comparison of parameters of methods and results of photodynamic therapy in 2 randomized groups. Each group consisted of 45 patients. The research method was applied in the main group and the standard method was used in the comparison group. It was found that the research method allowed significant reduction of duration of irradiation compared with conventional method (at the average from 690±65sec to 470±45sec, p=0,02), though the treatment results were the same. The suggested method allowed separation of group of patients with absence of fluorescence of timorous tissue. Performance of photodynamic therapy is unreasonable for these patients.

Methods of surgical interventions performing, modifications, instruments used for operation became more developed every year. In spite of this fact, tendency of increase of the rate of iatrogenic errors took place and it was possible to prevent these mistakes by application of Surgical Safety Checklist. The «checklists» are easily available, not very expensive in practice and they are simple to use. An application of such questionnaires could improve the team work and understanding between members of the crew, which could influence directly on operation outcome. The article presents the history of creation of safety list, the analysis of efficacy of «checklist» application in clinical practice in different countries, information about controversial questions in «checklist», perspectives of its application.

The article presents an assessment of postoperative period in patients with diffuse lung emphysema with large and giant bullas on the basis of surgical risk criteria, which were developed for the patients with diffuse emphysema without bullas. Retrospective study determined the group of patients who had high rate of surgical complications after bullectomy. The patients (46) were divided into 2 groups and it depended on the initial condition of the patients. There was stated, that the main criterion of surgical risk was a decrease of the level of OFL lower than 20% of the proper level in patients with large and giant bullas.

The article showed the results of ultrasonic assessment of topographic and functional diaphragm indices in patients with severe diffuse emphysema. They passed the selection for lung volume reduction surgery. The comparison of diaphragm indices was presented in patients with diffuse emphysema and control group of healthy volunteers. Dynamics of diaphragm condition was studied after surgical treatment. There wasn’t noted any statistical difference of diaphragm topographic indices as compared with the control group. There wasn’t shown a correlation between respiratory function indices and functional diaphragm indices, but it was noted a positive tendency in characteristics during quiet breathing.

Summary Objectives This report describes the result of prospective randomized trial to assess effectiveness and safety of neoadjuvant photodynamic therapy (PDT) and chemotherapy as well as possibility for further surgery for locally advanced NSCLC. Methods Patients with stage IIIA and IIIB central NSCLC (main bronchus/distal trachea involvement) who were not initially eligible for surgery but might be considered as surgery candidates after neoadjuvant therapy were enrolled in the study. They were randomized to either neoadjuvant chemotherapy and endobronchial PDT or chemotherapy alone followed by surgical resection. PDT was done with photosensitizer agent chlorine E6 and 662 nm laser light before each of the three courses of chemotherapy. Results From January 2008 to December 2011, 42 patients were assigned to PDT arm (n = 21) and No-PDT arm (n = 21). Groups were similar with respect to age, sex, tumor stage, and histology. No PDT major complications were observed. After neoadjuvant treatment partial response revealed in 19 pts (90%) in PDT arm and 16 pts (76%) in No-PDT arm (p = 0.460), these patients underwent thoracotomy. After thoracotomy tumor was unresectable in 3 pts of No-PDT arm (19%). There were 14 pneumonectomies and 5 lobectomies in PDT arm vs. 10 pneumonectomies and 3 lobectomies in No-PDT arm. Completeness of resection was significantly higher in PDT arm (R0-89%, R1-11%) vs. No-PDT arm (R0-54%, R1-46%), p = 0.038. Conclusions The study demonstrated that neoadjuvant PDT along with chemotherapy is effective, safe and it makes possible to convert to surgery candidates and to improve resection completeness in stage III central NSCLC patients.

To develop the new method of laser recanalization of airways for tumoral stenosis.It is proposed to conduct laser effect in the gas environment that does not support combustion (argon). Also the device for these AIM: is suggested. The method is called argon-laser ablation (ALA). A comparison of ALA and conventional high-energy laser exposure (LPD) was performed.ALA and LPD were used in 46 patients and 17 patients with non-small cell lung cancer. The duration of endobronchial operations and incidence of complications were significantly higher in group 2. The incidence of complete remission was significantly higher in group 1.Endobronchial argon-laser ablation of tracheal and bronchial tumors removes exophytic tumoral component in more favorable conditions compared with conventional high-energy laser exposure. Also it significantly increases an efficiency and reduces the frequency of complications.Цель исследования - разработка нового метода лазерной реканализации дыхательных путей при их опухолевых стенозах. Материал и методы. Предложено проводить лазерное воздействие в среде газа, не поддерживающего горение (аргона), а также разработано устройство для реализации метода. Способ назван аргонолазерной абляцией (АЛА). Проведено сравнение результатов АЛА и традиционного высокоэнергетического лазерного воздействия - лазерной фотодеструкции (ЛФД). Результаты. АЛА проведена 46 (1-я группа), ЛФД - 17 (2-я) больным немелкоклеточным раком легкого. Длительность эндобронхиальных операций (ЭБО) и частота осложнений оказались достоверно выше у больных 2-й группы, а частота полных ремиссий достоверно чаще имела место у больных 1-й. Вывод. Метод эндобронхиальной АЛА новообразований трахеи и крупных бронхов позволяет удалять экзофитный компонент опухоли в более благоприятных по сравнению с ЛФД условиях, способствует существенному повышению эффективности и снижению частоты осложнений.Цель исследования - разработка нового метода лазерной реканализации дыхательных путей при их опухолевых стенозах. Материал и методы. Предложено проводить лазерное воздействие в среде газа, не поддерживающего горение (аргона), а также разработано устройство для реализации метода. Способ назван аргонолазерной абляцией (АЛА). Проведено сравнение результатов АЛА и традиционного высокоэнергетического лазерного воздействия - лазерной фотодеструкции (ЛФД). Результаты. АЛА проведена 46 (1-я группа), ЛФД - 17 (2-я) больным немелкоклеточным раком легкого. Длительность эндобронхиальных операций (ЭБО) и частота осложнений оказались достоверно выше у больных 2-й группы, а частота полных ремиссий достоверно чаще имела место у больных 1-й. Вывод. Метод эндобронхиальной АЛА новообразований трахеи и крупных бронхов позволяет удалять экзофитный компонент опухоли в более благоприятных по сравнению с ЛФД условиях, способствует существенному повышению эффективности и снижению частоты осложнений.

Many of thoracic minimally invasive interventions have been proven to be possible without general anesthesia. This article presents results of video-assisted thoracic surgery (VATS) application under local anesthesia in patients with lung abscesses and discusses its indications in detail.The study involved prospective analysis of treatment outcomes for all acute infectious pulmonary destruction (AIPD) patients undergoing VATS under local anesthesia and sedation since January 1, 2010, till December 31, 2013. Patients with pulmonary destruction cavity at periphery of large size (5 cm) underwent non-intubated video abscessoscopy (NIVAS). Patients with pyopneumothorax (lung abscess penetration into pleural cavity) underwent non-intubated video thoracoscopy (NIVTS). Indications for NIVAS and NIVTS were as follows: cavity debridement and washing, necrotic sequestra removal, adhesion split, biopsy. All interventions were done under local anesthesia and sedation without trachea intubation and epidural anesthesia.Sixty-five enrolled patients had 42 NIVAS and 32 NIVTS interventions, nine patients underwent two surgeries. None of the patients required trachea intubation or epidural anesthesia. In none of our cases with conversion to thoracotomy was required. Post-surgical complications developed after 11 interventions (13%): subcutaneous emphysema (five cases), chest wall phlegmon (three cases), pulmonary bleeding (two cases), and pneumothorax (one case). One patient died due to the main disease progression. In 50 patients NIVAS and NIVTS were done within 5 to 8 days after abscess/pleural cavity draining, while in other 15 patients-immediately prior to draining; both pulmonary bleeding episodes and all cases of chest wall phlegmon took place in the latter group.NIVAS and NIVTS under local anesthesia and sedation are well tolerated by patients, safe and should be used more often in AIPD cases. Timing of NIVAS and NIVTS procedures was found to be of paramount importance for ensuring complete therapeutic effectiveness.

To analyze early postoperative period in patients with diffuse pulmonary emphysema after palliative surgical correction of respiratory failure.The study included 196 patients who underwent bullectomy (n=111) and surgical reduction of pulmonary volume (n=85).Overall morbidity and mortality were 40.8% and 12.2% respectively. Among patients older than 60 years these values were significantly higher (58.0% and 22.6% respectively). It was shown that age over 60 years is associated with high risk of complications and mortality after excision of large and giant bulls. In patients60 years morbidity is comparable after bullectomy and surgical reduction of pulmonary volume.Selection of patients for palliative surgical correction of respiratory failure is generally corresponded to that for lung transplantation. However, these methods should be considered complementary rather competing.Цель исследования - анализ раннего послеоперационного периода у пациентов с диффузной эмфиземой легких после паллиативной хирургической коррекции при дыхательной недостаточности. Материал и методы. В исследование включены 196 пациентов, которым выполнены буллэктомия (n=111) и хирургическая редукция объема легких (n=85). Результаты и обсуждение. Среди всех оперированных частота осложнений и случаев летального исхода составила 40,8 и 12,2%. В группе пациентов старше 60 лет эти показатели существенно выше (58,0 и 22,6%). Показано, что возраст пациентов старше 60 лет является критерием, связанным с высоким риском осложнений и летального исхода после удаления крупных и гигантских булл. Частота послеоперационных осложнений у пациентов моложе 60 лет после буллэктомии и хирургической редукции объема легких сопоставимы. Вывод. Отбор пациентов для паллиативной хирургической коррекции при дыхательной недостаточности в целом соответствует принципам отбора для трансплантации легких, но эти методы должны рассматриваться не как конкурирующие, а как дополняющие друг друга.

Neuroendocrine carcinomas combine a heterogeneous group of tumors occurring in lungs on a rare occasion, and in some cases, they appear to have extraordinary quick growth and extrapulmonary localization. In this case we present a 42-year-old patient who underwent a right upper lobectomy for emphysema, and 6 months later, the tumor developed again into a giant neuroendocrine carcinoma of the mediastinum.

Aim. To evaluate safety and effectiveness of combined treatment of non-small cell lung cancer (NSCLC) including chemotherapy and endobronchial PDT. Methods. Results of treatment for two groups of patients with central advanced NSCLC were compared, 75 patients in each. In arm A first line chemotherapy with endobronchial photodynamic therapy (PDT) was done, in arm B - chemotherapy only. PDT was performed with the use of chlorine based photosensitizers in the dose of 1 mg/kg body weight. Results. Investigated groups were comparable. No serious PDT complications were observed. The number of patients progression (p=0,05) was significantly different in favour of arm A. Remission in arm A was noted in 90% of patients, in arm B - in 76% (p=0,02). One-year survival was 60% and 41% for groups A and B, respectively (р=0,03). Conclusion. Combination of endobronchial PDT and chemotherapy is safe and effective, makes possible to improve results of treatment and survival in central advanced NSCLC.

Current views on mechanisms of therapeutic effect of photodynamic therapy for treating of cancer patients are represented. The history of formation and development of the method is described. The main requirements for agents used as photosensitizers are listed. Detailed review of main photosensitizers used in clinical practice in Russia and in foreign countries with their chemical structure, main spectral characteristics was performed. Methods of its application, therapeutic dose ranges, indications, specifi c pharmacokinetic properties and side-effects are briefl y outlined. Advantages and disadvantages of the most popular modern photosensitizers, main mechanisms of entry of photosensitizers of different chemical structure into cancer cells are observed. Three main possible component of anti-tumor effect: direct damage of cancer cells, impairment of vascular stroma of tumor and elimination of tumor due to immune cells are shown and closely discussed. Necrosis and apotosis of neovascular net which are main development trends of anti-tumor action for photodynamic therapy are noticed.

The authors investigated features of diagnostics and surgical treatment of lung cancer which was complicated by purulent destructive process. The possibilities of radical operative intervention were considered after preliminary adequate treatment of purulent complications in 226 patients. It was noted, that the diagnostic thoracotomy should be used in doubtful cases in order to estimate the resectability of lung cancer.

The article presents the results of the first domestic experience of intraoperative fluorescence mapping of sentinel lymph nodes in lung cancer. The research included 10 patients, who underwent surgery over the period of time from September 2013 to May 2014. After performing thoracotomy, the solution of indocyanine green (ICG) was injected using subpleural position above the tumor in 3-4 points. Fluorescence (ICG) image guided surgery was carried out by using infrared radiation (wave length 808 nm) on lung surface, root of lung, mediastinum in real time. Fluorescence lymph nodes were mapped. In case that metastatic lesions weren’t revealed in sentinel lymph nodes, they weren’t noted in other nodes. Method specificity consisted of 100%. Biopsy and histological study of sentinel lymph nodes mapped during fluorescence (ICG) image guided surgery could be useful for prevention of lymphodissection in patients with non-small cell carcinoma of lung.

An analysis of the scientific data was made. It was used the literature devoted to the intraoperative visualization of the sentinel lymph nodes in patients with lung cancer. Correct detection of such lymph nodes with following pathologic investigation allowed limiting the volume of lympho-dissection in a number of patients. There is the possibility of maximal in-depth study of the sentinel lymph nodes by purposeful application of most sensible pathologic and molecular methods for detection their micro-metastatic lesions. At the same time the treatment strategy and prognosis could be determined. The authors present the results of an application of dye techniques, radioactive preparation and fluorescence imaging for sentinel lymph node detection. Advantages and disadvantages of the methods are shown in the article. There are validated the prospects of technical development, study of information value of new applications and the most perspective method of fluorescence indocyanine green visualization by lymph outflow.