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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 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.

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

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.

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.

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.

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.

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.