Metastasectomy is a recommended and widely used operation for pulmonary metastases from colorectal cancer (CRC). The main disadvantage of pulmonary metastasectomy is the high rate of metastasis recurrence, which occurs in almost half of patients. To suppress residual pulmonary microfoci, isolated lung chemoperfusion (ILuP) is used, but its effectiveness has not been studied.The results of pulmonary metastasectomy were studied in 160 patients. In 65 patients of the main group, open metastasectomy with isolated chemoperfusion of the lungs was performed; in 95 patients of the control group, standard open or thoracoscopic metastasectomy was performed. The study design included 1:1 pseudorandomization using the nearest neighbor method. For 17 patients who underwent standard metastasectomy and then metastasectomy with ILuP for recurrent pulmonary metastases, these patients themselves were used as the nearest neighbor. For the remaining patients, the matching pairs were selected by the Propensity Score Matching method. After balancing the sample, the main and control groups comprised 41 pairs of observations, which were subjected to further analysis with assessment of relapse-free pulmonary survival according to Kaplan-Meier. Factors influencing survival were studied in the Cox's model.The median recurrence-free survival in patients of the main group who underwent metastasectomy with ILuP was 22.3 months versus 9.1 months in the control group. One-year recurrence-free survival in the main group was 77.5 ±  6.6% versus 38.1 ± 9.1% in the control group.Isolated lung chemoperfusion increases median recurrence-free survival after pulmonary metastasectomy by more than one year for colorectal cancer.

В данном разделе указаны критерии оценки клинической значимости применения дорогостоящей противоопухолевой лекарственной терапии в соответствии со шкалой, разработанной экспертной группой (см. стр. 7). В тексте они обозначены, как магнитуда клинической значимости (МКЗ).

8057 Background: The nonrandomized phase 2 KEYNOTE-799 study (NCT03631784) of pembro + cCRT in previously untreated unresectable, locally advanced, stage III NSCLC demonstrated an ORR of 70.5% in cohort A (squamous and nonsquamous) and 70.6% in cohort B (nonsquamous only) after median follow-up of 18.5 mo and 13.7 mo, respectively. We present outcomes with ⁓4 y of follow-up and analysis of ctDNA. Methods: Eligible patients (pts) were aged ≥18 y with unresectable confirmed stage IIIA–C NSCLC (per AJCC v8), measurable disease per RECIST v1.1, and ECOG PS 0 or 1. Pts in cohort A (squamous and nonsquamous) received carboplatin + paclitaxel and pembro 200 mg for one 3-wk cycle, followed by carboplatin + paclitaxel QW for 6 wks + 2 cycles of pembro 200 mg Q3W + standard thoracic radiotherapy (TRT). Pts in cohort B (nonsquamous only) received 3 cycles of cisplatin, pemetrexed, and pembro 200 mg Q3W + standard TRT in cycles 2 and 3. All pts received 14 additional cycles of pembro. Primary endpoints were ORR per RECIST v1.1 by BICR and incidence of grade ≥3 pneumonitis (per NCI CTCAE v4.0). As an exploratory endpoint, tumor ctDNA was assessed in available plasma samples collected at baseline and cycle 7 using the Signatera ctDNA assay. Results: Of 214 pts enrolled, including 112 in cohort A and 102 in cohort B. Median (range) time from first dose to database cutoff (Oct 16, 2023) was 54.1 (49.2–59.4) and 49.3 (38.4–59.1) mo, respectively. ORR was 71.4% in cohort A and 74.5% in cohort B (Table). Grade ≥3 pneumonitis (primary endpoint) occurred in 9 pts (8.0%) in cohort A and 7 (6.9%) in cohort B. Grade 3–5 treatment-related AEs occurred in 73 pts (65.2%) in cohort A and 52 (51.0%) in cohort B. Of ~136 samples sent for sequencing, 73 pts (~53.7%) had samples evaluable for ctDNA at baseline. ORR was 68.7% in pts with ctDNA detectable (n = 67) vs 50.0% in pts with ctDNA non-detectable samples (n = 6) at baseline. Among 46 pts with ctDNA detectable at baseline and evaluated at cycle 7, 32 (69.6%) had cleared ctDNA at cycle 7; these pts had better trends in PFS and OS vs pts who had not cleared ctDNA at cycle 7 (n = 14). Conclusions: With ~4 y of follow-up, pembro + cCRT continues to demonstrate durable antitumor activity and manageable safety in previously untreated unresectable, locally advanced stage III NSCLC. ctDNA was evaluable in ~half of the samples assessed; most pts with detectable ctDNA at baseline had cleared ctDNA at cycle 7. Clinical trial information: NCT03631784 . [Table: see text]

An anastomosis forming between right upper lobe bronchus, trachea and left main bronchus.

Background: Bronchoplastic resections are now widely used as a surgical treatment for resectable central lung cancer. However, bronchial dehiscence is one of the most life-threatening complications, making it important to identify its risk factors to separate patients who require more attention during the postoperative period. Methods: The data of 285 patients who underwent bronchoplasty from 2006 to 2021 were retrospectively reviewed. We collected demographic characteristics, history of neoadjuvant therapy, preoperative assessment, perioperative outcomes, and postoperative complications to investigate different variables as risk factors for bronchial dehiscence by univariate and multivariate analyses. Results: Bronchial dehiscence was diagnosed in 12 patients (4.2%) with a mean presentation on postoperative day 10 (range: 1–24 days). By multivariate analysis, current smoking (odds ratio (OR): 4.8, 95% confidence interval (CI): 1.1–20.1, p = 0.032), chronic obstructive pulmonary disease (OR: 6.5, 95% CI: 1.2–33.8, p = 0.027), bronchoplastic right lower lobectomy (OR: 12.9, 95% CI: 2.4–69.7, p = 0.003), and upper sleeve bilobectomy with segmentectomy S6 by performing an anastomosis between right main bronchus and bronchus of basal pyramid (OR: 30.4, 95% CI: 3.4–268.1, p = 0.002) were confirmed as relevant risk factors for developing bronchial dehiscence. Conclusions: Current smoking, COPD, bronchoplastic RLL, and upper bilobectomy with segmentectomy S6 by performing an anastomosis between RMB and bronchus of BP were identified with the occurrence of bronchial dehiscence after sleeve resection.

11568 Background: The combination of pulmonary metastasectomy (ME) with isolated lung chemoperfusion (ILuP) has shown promising results, however, a direct comparison of the clinical outcomes obtained by ME plus ILuP versus ME alone is complicated. The heterogeneity of patients in terms of cancer types, number of metastases and composition of prior systemic therapy adds to the difficulties of this analysis. Methods: Patients who initially received ME alone, and then ME plus normothermic ILuP after the disease relapse, were considered. The aim of the study was to compare the time to pulmonary disease progression (TTP) after the first and second interventions (TTP1 and TTP2, respectively) in the same subjects. Results: Of 225 patients who underwent ME plus ILuP in 2007 - 2020, we selected 48 patients who received this treatment due to pulmonary disease progression after ME alone. There were 16 patients with soft tissue sarcoma, 8 patients with osteosarcoma, 14 colorectal cancer cases and 10 patients with other tumor types. The mean number of metastases was 2.94 before ME alone and 4.33 before ME plus ILuP. Cisplatin was used in 30 patients at a mean dose of 191.8 mg, and melphalan was utilized in 18 subjects at a mean dose of 44.1 mg. The median follow-up was 31.1 months. The median TTP1 was 6.9 months, and the median TTP2 was 19.0 months (p <0.0001). TTP2/TTP1 ratio equal or above 1.5 was observed in 34 out of 48 patients (71%). Conclusions: This is the first study comparing the results of ILuP plus ME versus ME alone in the same patients. The data obtained strongly support the feasibility of adding isolated lung chemoperfusion to surgery in patients amenable to excision of lung metastases.

Objective. To assess the overall and disease-free survival rates in patients with EGFR-mutated lung adenocarcinoma, who underwent surgery after achieving the objective response to tyrosine kinase inhibitor (TKI) therapy. Material and Methods. The overall and disease-free survival rates were analyzed in 18 patients with EGFR-positive lung adenocarcinoma, which was inoperable at presentation due to locally advanced disease or the evidence of distant metastasis. In accordance with the clinical standards, patients were recommended for TKI therapy. Surgical resection was performed after achieving the objective tumor response to TKI therapy. The control group included 23 patients with EGFR mutation-positive lung adenocarcinoma, who did not undergo surgery after receiving TKI therapy. Results. The study revealed a statistically significant effect of surgical resection on the overall survival (OS) in patients with EGFR mutation-positive stage III–IV lung adenocarcinoma after response to TKI therapy (p=0.004). However, there was no statistically significant effect on the disease-free survival (DFS) (p=0.40). There was a tendency to increase in the median OS in patients of the study group (46 months) compared to that in patients of the control group (26 months). Surgery in the study group was characterized with some technical difficulties associated with severe fibrosis. However, this did not affect the duration of surgery and the volume of blood loss. Conclusion. Tumor resection in patients with EGFR mutation-positive stage III–IV lung adenocarcinoma is feasible and safe, but requires highly qualified team surgeons in well-equipped medical centers. Our study revealed that the combination of EGFR-TKI and tumor resection provided better PFS and OS than EGFR-TKI alone. However, further studies are required.

The tasks of surgical treatment include oncological radicality, resectability, safety. Surgical approach and esophagectomy techniques, risks and benefits of lymphadenectomy volume, the need for sufficient clearance from the tumor, the functional and anatomical features of gastric conduit, the advantages and disadvantages of the gastric conduit routes and the level of anastomosis formation, neoadjuvant therapy should be considered. The study included 300 cases who experienced extended hybrid or complete minimally invasive esophagectomy with gastric conduit reconstruction. Prospective arm included 119 patients who experienced surgery in 2018-2022 when surgery type selection was worked out by algorithm; retrospective arm included 126 subjects with surgery performed in 2012-2017, when proposed algorithm had not been implemented. The population of the arms was similar by the age, sex, amount, staging, histology, type of surgery (p>0,05). The analyzed results were depended on: the surgical approach (minimally invasive, hybrid minimally invasive), esophagectomy technique (by McKeown, Lewis), lymph node dissection volume (2S, 2F, 3F), clearance from the tumor, the width of gastric conduit (wide or narrow), the route of the gastric conduit (retrosternal and right intrapleural), the level of anastomosis formation (neck and pleural cavity, the neoadjuvant therapy program (the fact of radiation therapy). Adverse events were assessed by Katayama-Clavien-Dindo scale. The algorithm of surgery type selection was worked out. Only the upper thorax esophageal cancer is reasonable for McKeown procedure with cervical anastomosis and narrow gastric conduit. Due to perfusion disorders provoked by radiation therapy and distance from the blood supply point cervical anastomosis leak is a frequent complication but can be cured as salivary fistula after proper drainage. The analyzed data insisted to refuse unreasonable McKeown procedure and narrow gastric conduit formation: 64 procedures performed before the algorithm implementation and only 25 after it. This is one of the reasons in anastomotic leak rate decrease. The middle thorax esophageal cancer should be operated by Lewis procedure with anastomosis in thoracic aperture with wide gastric conduit. Lower thorax cancer is also operated with Lewis procedure, but anastomosis should be formed at the level of tracheal bifurcation. Abdominal and cardioesophageal cancer require resection of small curvature with anastomosis formed below tracheal bifurcation. R0 resection rate achieved 99 % in algorithm group and 98 % in the group without algorithmic surgery tactic selection (p>0,05). Postoperative mortality reduced from 11,5 % in 2012-2017 to 5,9 % (p < 0,05). Anastomotic leakage decreased from 19,8 % with 7,1 % mortality rate among the cases of the retrospective group to 13,4 % with 4,2 % mortality rate among the cases of the prospective group (p < 0,05). The overall complication rate measured by Katayama-Clavien-Dindo scale becomes less with percentage 56 % and 45,5 % respectively (p < 0,05). There was no statistical validity achieved in comparison of recurrence free survival and overall survival between arms grouped by the stage respectively. The implementation of the algorithm improves the results of surgical treatment of the esophageal cancer. It brought the reduction of general and esophagectomy-specific postoperative complications, especially anastomotic leakage, postoperative mortality, also brought the increase of oncological radicality.

Увеличение продолжительности жизни больных операбельным немелкоклеточным раком легкого (НМРЛ) после комплексного лечения сопряженно с нарушениями психологического и физического функционирования, снижающими общее качество жизни. В статье приводится оценка эффективности реабилитационных программ у больных операбельным НМРЛ с учётом рекомендованных технологий (РТ) физической и реабилитационной медицины (персонализированный подход) в сравнении со стандартным подходом к реабилитации. Материалы и методы. В исследование были включены 240 пациентов с операбельным НМРЛ в возрасте от 45 до 71 года (медиана 60,2 года), получавших реабилитацию в рамках комбинированного/комплексного лечения в ФГБУ «НМИЦ онкологии им. Н.Н. Петрова» Минздрава России в период с 2017 по 2022 гг. Пациентам в экспериментальной группе применялась персонализированная модель реабилитации. Согласно дизайну исследования в контрольную группу (стандартные реабилитационные мероприятия) были подобраны попарно пациенты, соответствующие больным экспериментальной группы по основным характеристикам: полу, возрасту, функциональному состоянию, гистологическому подтипу, стадии заболевания, объёму лечения. Динамика показателей пациентов была исследована в пред-/послеоперационный период, непосредственно после реализации программ реабилитации и через 1 год, включала оценку показателей клинического статуса (Шкала mMRC, Шкала COMP, ВАШ, 6-минутный тест ходьбы), функциональных (ФВД) и психофизиологических показателей (Шкала MFI-20, Шкала HADS), показателей качества жизни (EORTC-QLQ30). Результаты. Анализ показателей эффективности реабилитации больных НМРЛ показал, что в экспериментальной группе (персонализированная модель реабилитации), реабилитация была эффективна у 86 % пациентов, в то время как в контрольной группе (стандартные программы реабилитации) — в 76 % случаев. Основными детерминантами, влияющими на формирование лечебного эффекта после применения реабилитационных программ, составленных с учётом выбранных РТ, являются параметры функции внешнего дыхания (ЖЕЛ — жизненная емкость легких, МОС — максимальная объемная скорость на выдохе, СОС — средняя объемная скорость при выдохе), показатели теста 6-минутной ходьбы, шкал выраженности одышки (Modified Medical Research Council, mMRC) и выполнения повседневной деятельности (Canadian Occupational Performance Measure, COMP). Вывод. Выделенные детерминанты позволят заблаговременно спрогнозировать эффективность реабилитационных технологий у конкретной модели пациентов операбельным НМРЛ с учётом исходных параметров.

Creating a disease models based on real-world clinical data from the moment of diagnosis is an important task of the healthcare system, it allows to simulate the quantitative need for hospitalizations with various options for necessary treatment and calculate the approximate amount of necessary funding.The study aimsto build a model calculating the necessary volumes of medical care and funding for inpatient treatment of patients with lung cancer.Materials and methods.Anonymized data from the territorial compulsory medical insurance fund and the Department of high-tech medical care for all cases of lung cancer and metastases of any localization (ICD-10: C34 and C77-78) for residents of St. Petersburg, who received medical care from 2011 to 2020. Data from the population cancer registry database for all lung cancer patients in St. Petersburg since 2000.Results.More than 75 % of hospitalizations occur within 1 year from the moment of diagnosis: 68 % — chemotherapeutic treatment, 17 % — surgery, 3 % — radiotherapy. In the first year, 1 patient with stages I and II has an average of 2 hospitalizations, III and IV — 3. The calculated by the model number of hospitalizations in the 2 236 lung cancer patients in 5 years is 7 108. Payment for inpatient care based on the tariffs of the federal fund of 2022 and the number of newly diagnosed lung cancer diagnoses for five years will cost the healthcare system 1.1 billion RUR, and more than 74 % of this amount is the cost of 1 year of treatment. During the 5 years, surgery will cost 145 million RUR, chemotherapy — more than 898 million RUR, and radiotherapy — 37 million RUR.Conclusion.The developed on the real-world clinical data model can be used to calculate the necessary healthcare needs and its costs.

IMpower010 showed significant DFS benefit with atezo after adjuvant chemo in resected NSCLC (Felip Lancet 2021). At the interim DFS analysis, the significance boundary was crossed for the stage II-IIIA PD-L1 TC ≥1% population (stratified HR, 0.66; 95% CI: 0.50, 0.88), with greatest benefit in the PD-L1 TC ≥50% subgroup (unstratified HR, 0.43; 95% CI: 0.27, 0.68). Here we present further analyses in PD-L1 TC ≥50% stage II-IIIA NSCLC pts.

The study objective – to analyze the treatment results and prognostic factors of survival in patients with locally advanced laryngeal cancer who received surgical treatment and chemoradiotherapy.Materials and methods. The retrospective study included patients with locally advanced laryngeal cancer treated at the N. N. Petrov National medical Research Center of Oncology, Ministry of Health of Russia in the period from 2009 to 2018. The patients included in the study were divided into 2 equal groups (74 patients were included in each group) depending of treatment: surgery with postoperative radiation therapy combined with chemotherapy (group 1) and concurrent chemoradiation therapy and subsequent surgical treatment in case of incomplete response to treatment or disease progression (group 2). The endpoints of the study were general and relapse-free survival.Results. One hundred and forty-eight patients were included in the study: 74 patients in group 1 and 74 patients in the group 2. The median overall survival in the surgical treatment group was 45 months, in the chemoradiotherapy group – 44.6 months, and the overall 5-year survival for the group 1 and the group 2 were 39.3 (95 % confidence interval (CI) 26.1–59.2), and 59.2 % (95 % CI 45.3–77.2), respectively. The relapse-free 5-year survival rate for the surgical treatment group and the chemoradiotherapy group was 36.8 (95 % CI 25.1–53.8), and 53.9 % (95 % CI 40.7–71.4), respectively.Conclusion. There were no significant differences in overall and relapse-free survival. Metastatic lesion of the neck lymph nodes (N2–3), invasion of laryngeal cartilage, invasion of the thyroid gland and the spread of the tumor to the larynx are statistically significantly associated with lower overall and relapse-free survival.

Introduction. Lung cancer (LC) is one of the leading causes of mortality in Russia and in all other the world. Late detection of LC is a healthcare system issue because of most of patients are asymptomatic. Aim. The aim of the study was to analyze the structure of healthcare resources in the group of patients with non-small cell LC (NSCLC) in St. Petersburg. Materials and methods. The database of electronic medical records was created by combining the information from National cancer register and governmental medical insurance system, which included the patient with NSCLC diagnosed between 2011 and 2020 years. The data about the high technology medical services received by patients was added in the database as well. Results. None of the existing electronic medical records system is able to make visible all the medical services received by a specific patient. The combined database gives the possibility to follow-up the history of around 8000 patients with NSCLC in St. Petersburg. Conclusions. When building the hospital model of the NSCLC patient aiming the rational planning of healthcare resources the stage of the disease is the most important because it is strongly linked with the healthcare resources provided to the patient.

Objective. Analyze the frequency and prognostic factors of complications in patients with locally advanced cervical esophageal cancer after pharyngolaryngoesophagectomy with simultaneous reconstruction of the defect.Material and methods. The retrospective study included patients with a verified locally advanced cervical esophageal cancer who were treated at the N. N. Petrov National Research Institute of Oncology in the period from 2009 to 2018, who underwent surgical treatment followed by chemoradiotherapy. The end point of the study was the frequency of postoperative complications.Results. Forty-eight patients were included in the study. All patients underwent laryngopharyngoesophagectomy with simultaneous reconstruction of the digestive tract. Forty-one patients (85.4 %) underwent the reconstructive stage using a narrow gastric stalk, and a wide gastric stalk and a small intestine graft were used in 5 (10.4 %) and 2 (4.2 %) patients, respectively. The average duration of the operation was 390 (337.5–525.0) minutes, the volume of blood loss was 300 (200–500) ml, and the average time of hospitalization and the patient’s stay in the intensive care unit was 21.5 (16.00–36.00) and 3 (1.000–6.75) days, respectively. Complications within 30 days after surgical treatment were observed in 54.1 % of patients, while anastomosis failure, fistula formation and pneumonia were observed in 22.9 %, 12.5 % and 18.8 % of cases, respectively. Factors slightly increasing the likelihood of pneumonia in the early postoperative period were: duration of surgery [OR = 1.0 (95 % CI: 1.00–1.01), p = 0.0131] and intraoperative blood loss [OR = 1.0 (95 % CI: 1.00–1.01), p = 0.0017].Conclusion. The overall complication rate after pharyngolaryngoesophagectomy with simultaneous repair of the defect by bioengineered graft was 54.1 %. Intraoperative blood loss and duration of surgery were associated with an increased risk of complications.

Purpose/Objective(s) Primary analysis (database cutoff, Oct 28, 2020) of the global KEYNOTE-799 study (NCT03631784) in patients (pts) with unresectable, locally advanced stage III NSCLC, showed that pembrolizumab (pembro; anti–PD-1) + cCRT resulted in an ORR of 70.5% in cohort A (n = 112; squamous and nonsquamous) and 70.6% in cohort B (n = 102; nonsquamous only) and grade ≥3 pneumonitis in 9 (8.0%) and 7 (6.9%) pts, respectively. We evaluated outcomes with 1 y of additional follow-up. Materials/Methods In this nonrandomized, phase 2 study, eligible pts were aged ≥18 y with previously untreated, unresectable, pathologically confirmed, stage IIIA-C NSCLC with measurable disease per RECIST v1.1. Pts in cohort A (squamous and nonsquamous) received carboplatin AUC 6 + paclitaxel 200 mg/m2 and pembro 200 mg for one 3-wk cycle, followed by carboplatin AUC 2 + paclitaxel 45 mg/m2 QW for 6 wks + 2 cycles of pembro 200 mg Q3W + standard thoracic radiotherapy (TRT). Pts in cohort B (nonsquamous) received 3 cycles of cisplatin 75 mg/m2, pemetrexed 500 mg/m2, and pembro 200 mg Q3W + standard TRT in cycles 2 and 3. All pts received 14 additional cycles of pembro 200 mg Q3W. Primary endpoints were ORR per RECIST v1.1 by blinded independent central review and the incidence of grade ≥3 pneumonitis (per NCI CTCAE v4.0). Results Of 216 pts enrolled, 112 in cohort A and 102 in cohort B received treatment. Median (range) time from first dose to database cutoff (Oct 18, 2021) was 30.2 (25.3–35.5) mo in cohort A and 25.4 (14.5–35.2) mo in cohort B. ORR (95% CI) was 71.4% (62.1%–79.6%) and 75.5% (66.0%–83.5%), respectively. Median duration of response (DOR) and OS were not reached (NR) in both cohorts; median PFS was 30.6 mo in cohort A, and NR in cohort B (Table). ORR was 66.7% in pts with PD-L1 TPS <1% and 77.3% in pts with PD-L1 TPS ≥1% in cohort A and 78.6% and 72.5%, respectively, in cohort B. ORR was similar by histology (squamous, 72.0%; nonsquamous, 74.1%). Grade ≥3 pneumonitis occurred in 16 pts (7.5%) overall; 9 pts (8.0%) in cohort A and 7 (6.9%) in cohort B. Treatment-related grade ≥3 AEs occurred in 64.3% and 51.0% of pts in cohort A and B, respectively. Data on TRT, including techniques utilized and details for organs at risk with and without pneumonitis, will be presented. Conclusion With >2 y of follow-up, pembro + cCRT continues to demonstrate robust and durable responses, regardless of PD-L1 TPS and tumor histology, promising survival outcome and manageable safety in pts with previously untreated, locally advanced stage III NSCLC.