Incidence of Synchronous Multiple Primary Melanoma in Patients with Solitary Melanoma: a Prospective Comparative Study

Background. Malignant melanoma is steadily exaggerating over the recent decades. Nonetheless, improved systemic therapies have substantially increased life expectancy in patients with a locally advanced or disseminated disease. Higherincidence recurrent melanocytic skin lesions become essentially problematic and require more attention and control.Aim. Cross-survey on the incidence of synchronous multiple primary melanomas in patients with solitary melanoma and those with other operable solid tumours.Materials and methods. A total of 289 patients with suspected malignant pigmented skin melanoma were included in the survey. Patients were divided in two cohorts by the presence of primary skin melanoma and its tractability for radical excision. Patients with operable melanoma comprised the study cohort, and those with other solid tumours were the control.Results and discussion. The survey covered 289 patients, with 148 in the study and 141 in the control cohort. The study148 patients revealed 112 malignant pigmented melanomas, but none in the control cohort. A chi-square statistical analysis of clinical values in single and multiple melanoma cases showed a slightly higher prevalence of first-visit melanomas in patients with synchronous tumours (30% pT4 — p = 0.007).Conclusion. The observed 10% rate of second melanoma in the study cohort and a zero melanoma incidence in the control support the alternative hypothesis of a higher rate of newly detected melanomas in primarily diagnosed melanoma patients vs. those with solid tumours

Efficacy of Videoendoscopic Inguinal Femoral Lymphadenectomy for Management of Metastatic Skin Melanoma

Aim. Assessment of the utility and advantage of videoendoscopic inguinal femoral lymphadenectomy (VE-LAD) over the standard open technique (OLAD) in patients with malignant skin melanoma and metastatic lesions of regional inguinal and/or femoral lymph nodes.Materials and methods. The Saint-Petersburg Clinical Research Centre for Specialty Medical Aid in Oncology managed 86 inguinal femoral LADs in melanoma patients over 2013–2016. VE-LAD was rendered in 48 (54.7 %) cases, and OLAD otherwise.Results and discussion. A total of 72 patients were included in the study. VE-LAD was performed in 48 (54.7 %) cases, and OLAD otherwise. An average VE-LAD duration was 90 (60 to 160) min. Severe complications were observed in 4/48 (8 %) VE-LAD and 16/24 (66 %) OLAD cases, which reveals a significantly lower complication rate in the study cohort (chi-square p > 0.000). Lymphorrhoea was shorter in the study cohort (> 7 days in 5 patients vs. 3/24 and > 14 days only in 11/24 OLAD cases; chi-square p > 0.000). No significant differences in relapse-free survival were observed between the cohorts, with higher absolute values of 22.6 months in the VE-LAD (95 % CI 14.8–30.4, p = 0.087) vs. 9.4 months (95 % CI 0.0–18.9, p = 0.087) in OLAD cohort. A median OS was 52.3 months (95 % CI 30.5–74.1, p = 0.996) in the VE-LAD vs. 39.9 months (95 % CI 30.6–49.2, p = 0.996) in OLAD cohort.Conclusion. Videoendoscopic inguinal femoral lymphadenectomy allows a radical inguinal femoral lymph node removal alike in conventional surgical dissection. Our results indicate the method performance towards reduced postoperative wound complications. The oncological indicators are comparable to the traditional surgery cohort

Comprehensive Screening for COVID-19 at St. Petersburg Oncology Centre

Background. Clinical reports on the coronavirus disease 2019 (COVID-19) suggest its higher incidence and worse outcomes in cancer patients. Considering a rapid pace of the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) pandemic, more data on the risk of contagion and syndrome course is required with this patient group.Aim. Estimation of the infection rate in cancer patients managed at the Oncology Centre.Materials and methods. This retrospective study included cancer patients managed at the Oncology Centre between 9 April 2020 and 27 May 2020 and routinely tested for SARS-CoV-2 in polymerase chain reaction (PCR) assays and/or COVID-19 in chest computed tomography (CT).Results and discussion. A total of 2,628 patients were included in the study, with 119 (4.5 %) confirmed to have COVID-19; 45/119 were PCR-positive, 95/119 had viral pneumonia in CT, 21/119 were positive for both tests. A total of 47.9 % cases were asymptomatic, 11.8 % revealed a mild single-symptom disease. COVID-19 ended in death in 2 (2.5 %) of 80 cases with a known outcome. In PCR results of both patient and staff screening, the virus detection rate was 3.0 % and 2.4 %, respectively (p = 0.33).Conclusion. A COVID-19 screening revealed no significant difference in the risk of contagion between cancer patients and staff of the Oncology Centre. PCR tests may perform false negative for COVID-19 in cancer patients and should be coupled with CT scanning. The infection is asymptomatic or clinically mild in most other cases

Результаты применения иммунотерапевтических препаратов при немелкоклеточном раке легкого в реальной клинической практике

The evolution of drug therapy in solid tumors primarily leads to the increase in cancer specific survival, but inevitably raises financial burden. So far, none of the countries can venture total reimbursement with all necessary contemporary drugs for all patients. Doubling of expenses for cancer drug therapy in Russia in 2019 allowed oncologists using the most expensive treatments in more than 70 % of patients.Purpose: To evaluate efficacy of various treatment types of non‑small cell lung cancer in real clinical setting.Material and methods. We included patients with histologically verified metastatic non‑small cell lung cancer without activating mutations treated with first or second line therapy in 2018 – 2019. In total 287 patients were included: 230 — for the first line efficacy analysis, 100 — for the second. Time to disease progression, overall survival and objective response rate were evaluated.Results. The use of checkpoint inhibitors in accordance with all actual recommendations (first line pembrolizumab monotherapy in PD-L1 > 50 %, chemoimmunotherapy in first line or monotherapy in the second line irrespectively to PD-L1 status) decreased one‑year mortality from 61 % in 2018 to 33 % in 2019, but significantly increased financial cost (p < 0.000). Moreover, checkpoint inhibitors in combination with chemotherapy irrespectively of PD-L1 expression increased response rate (from 10 % and 21 % for monotherapy and platinum doublet, respectively, to 33,2 % for chemoimmunotherapy). PD‑1 inhibitors as monotherapy increased median time to disease progression (4,1 and 6,2 months for monotherapy with chemotherapy and platinum doublet, respectively, to 6,5 months and not achieved for chemoimmunotherapy and monotherapy with checkpoint inhibitors).Conclusion. More than doubling of financial costs spent for non‑small cell lung cancer treatment allowed access to contemporary treatment for all patients. Such unprecedented measures significantly improved efficacy, including double decrease of one‑year mortality. Nevertheless, rational design of regional clinical guidelines interpretation is of great importance in accurate and effective use of the healthcare budget.Совершенствование лекарственной терапии злокачественных опухолей позволяет существенно увеличить продолжительность жизни пациентов, но неминуемо ведет на ранних этапах внедрения к повышению затрат на лекарственное обеспечение. Ни одна из стран мира на настоящий момент не может позволить себе полное обеспечение новейшими лекарственными препаратами всех больных. Двукратное увеличение расходов на лекарственное лечение на территории РФ в течение 2019 года позволило обеспечить современными препаратами 70 % нуждавшихся пациентов немелколеточным раком легкого (НМРЛ).Цель. Оценить клиническую эффективность различных методов лекарственной терапии рака легкого в реальной клинической практике.Материалы и методы. В анализ включались пациенты с гистологически верифицированным неоперабельным НМРЛ, получавшие первую или вторую линию терапии в 2018–2019 гг. В исследование были включены 287 пациентов с НМРЛ: 230 больных для оценки эффективности первой линии, 100 — второй. Были оценены: время без прогрессирования, общая выживаемость, частота объективных ответов.Результаты. Применение ингибиторов контрольных точек в любом из зарегистрированных вариантов (первая линия при PD-L1 > 1 %, химиоиммунотерапия независимо от статуса PD-L1, вторая линия независимо от статуса PD-L1) позволяет снизить одногодичную летальность с 61 % до 33 %, однако приводит к достоверному увеличению затрат на лекарственное обеспечение (р< 0,000). Кроме того, использование ингибиторов контрольных точек в монорежиме у больных с высоким уровнем экспрессии PD-L1 или в комбинации с цитостатическими препаратами позволяло увеличить частоту объективных ответов (10 % и 21 % для монотерапии и платиновых дуплетов против 33,2 % для химиоиммунотерапии), медиану времени без прогрессирования (4,1 и 6,2 месяца для монотерапии и платиновых дуплетов против 6,5 месяцев для химиоиммунотерапии, тогда как медиана для монотерапии ингибиторами контрольных точек не достигнута).Выводы. Более чем 2-кратное повышение финансирования лекарственного лечения позволило обеспечить современными препаратами всех нуждавшихся пациентов НМРЛ. Подобные меры позволили достоверно увеличить продолжительность жизни больных НМРЛ. Тем не менее, рациональное использование подобных ресурсов требует выработки жестких критериев для того или иного дорогостоящего метода лечения

Оценка токсичности и эффективности терапии комбинацией FOLFIRI и афлиберцепта при метастатическом раке толстой кишки в РФ: первые результаты многоцентрового ретроспективного исследования

oai:oai.tumors.elpub.ru:article/629Purpose. To assess the incidence and severity of adverse events; to explore clinical factors associated with grade 3–4 non-hematologic toxicity; to assess the immediate efficacy and progression-free survival during treatment with the FOLFIRI regimen in combination with aflibercept in Russia.Materials and Methods. A retrospective multicenter study has been conducted with data collected from 20 clinics in 15 regions of Russia. There was no statistical hypothesis. Progression-free survival was the main efficacy criterion. The statistical analysis was performed using IBM SPPS Statistics v. 20 software.Results. FOLFIRI and Aflibercept combination was administered to 264 patients. The mean number of treatment cycles was 6 (1 to 29). The toxicity of aflibercept was addressed by dose reduction and dosing delay in 10.1 % and 11.4 % of patients, respectively, and dose reductions and dosing delays in any of FOLIFRI components were reported in 20.1 % of participants. The objective response rate was 20.3 %. The median progression-free survival in patients receiving second-line treatment was 6 months (95 % CI: 5.3–6.6 months). Seventy-two percent of patients experienced any grade of adverse events most of which were limited to grade 1–2 (62.1 %). Non-hematologic toxicity was reported in 64 % of patients (grade 3–4 in 17.9 %). Hematologic events were detected in only 17.9 % of patients. Multifactorial analysis has shown that drug therapy for concomitant diseases (OR 1.98, 95 % CI: 1.04–3.78, p = 0.037) and the number of chemotherapy lines prior to aflibercept (ОR 1.5, 95 % CI: 1.06–2.11, p = 0.02) were independent predictors of grade 3–4 non-hematologic toxicity.Conclusions. Objective response rate, progression-free survival, and frequency of toxicity-related aflibercept discontinuations in the Russian study with patients receiving aflibercept in combination with FOLFIRI regimen as a second-line treatment has shown the results that were comparable with VELOUR study. Comorbidities requiring drug treatment and the number of prior chemotherapy lines appear to be risk factors for grade 3–4 nonhematological toxicity events. Цель исследования. Оценить частоту развития и тяжесть нежелательных явлений; изучить клинические факторы, ассоциированные с развитием негематологической токсичности 3-4 степени; оценить непосредственную эффективность выживаемость без прогрессирования при применении комбинации FOLFIRI с афлиберцептом в РФ.Материалы и методы. Проведено ретроспективное многоцентровое исследование. Собраны данные 20 клиник 15 регионов РФ. Статистическая гипотеза отсутствовала. В качестве основного критерия эффективности рассматривалась выживаемость без прогрессирования. Статистический анализ проводился с помощью программ статистического пакета SPSS (IBM SPPS Statistics v. 20).Результаты. Режим FOLFIRI афлиберцепт был назначен у 264 пациентов. Среднее число составило 6 (от 1 до 29). В связи с токсичностью доза афлиберцепта в процессе терапии была редуцирована у 10,1% пациентов, задержали очередное введение афлиберцепта — у 11,4%; отсрочка и редукция доз химиопрепаратов в режиме FOLFIRI описана у 20,1 %. Частота объективных эффектов составила 20,3%. Во второй линии терапии медиана выживаемости без прогрессирования составила 6 месяцев (95% ДИ 5,3-6,6 месяцев). Нежелательные явления любой степени зарегистрированы у 72 % пациентов и чаще были ограничены 1-2 степенью (62,1%). Негематологические осложнения развились у 64% (3-4 степень — у 17,9%). Гематологические осложнения представлены только у 17,9 % пациентов. По результатам многофакторного анализа лекарственная терапия по поводу сопутствующей патологии (ОШ 1,98, 95%ДИ 1,04-3,78, р=0,037) и число линий терапии (ОШ 1,5, 95%ДИ 1,06-2,11, р=0,02), предшествующих афлиберцепту, явились независимыми предсказывающими факторами развития нежелательных явлений негематологического профиля 3-4 степени.Выводы. Частота объективных эффектов, выживаемость без прогрессирования и частота отмены афлиберцепта в связи с токсическими реакциями при применении комбинации FOLFIRI + афлиберцепт во второй линии среди пациентов в РФ аналогична результатам исследования VELOUR. Сопутствующая патология, требующая медикаментозной коррекции, и число линий терапии предшествующих афлиберцепту, по-видимому, являются факторами риска развития негематологических явлений 3-4 степени

COST-EFFICACY ANALYSIS OF GEFITINIB EFFICACY IN PATIENTS WITH NON OPERABLE NON SMALL CELL LUNG CANCER

Drug treatment of disseminated non small cell lung cancer  (NSCLC) is an actual  issue today.  Both clinical and economic efficacy analysis is needed for optimal therapy selection. We performed economic efficacy assessment of  gefitinib (G.)  therapy in patients with non operable NSCLC who hase no EGFR mutation using Markov model based  on results of clinical studies  conducted in N.N. Petrov Research Institute of Oncology.G. increases  overall survival of patients with NSCLC with EGFR mutation by 1,05 year. Cost/efficacy coefficient for  G. in patients with  EGFR mutation is 934  800  rub  per  1 acquired year  of  life. Therapy  with  G just for  patients with  genetically  proven  mutation is dominating strategy when  compared to  therapy for  all NSCLC patients  irrespectively to  mutation status (saving  211600 – 251800  rub per  1  patient taking  into  account equal clinical efficacy). Therapy  with  G. is economically  justifying  strategy when  compared to chemotherapy (additional costs coefficient 960700 – 1010000 rub per 1 gained year of life). Thus, EGFR mutation testing with subsequent G. therapy in non  operable NSCLC patients not only prolongs patient’s life but also has  acceptable level of medical expenses

Сonfirmatory study of the efficacy and tolerability of trifluridine/tipiracil (TAS-102) therapy in the Russian population with chemorefractory metastatic colorectal cancer

Introduction. Trifluridine/Tipiracil (FTD/TPI) is a new chemotherapeutic drug approved in more than 60 countries for use in patients with metastatic colorectal cancer who have registered progression or intolerance to treatment with fluoropyrimidines, oxaliplatin and irinotecan, anti-VEGRand anti-EGFR-targeted agents. This study evaluated for the first time the effectiveness and tolerability of FTD/TPI therapy in the Russian patient population.Materials and methods. A confirmatory open-label single-arm non-randomized trial was conducted in 2 clinical centres in Russia. The main criteria for inclusion were: conduction of at least the 2nd line of standard systemic therapy for metastatic colon adenocarcinoma. The primary efficacy criteria were: 2-month progression-free survival; secondary – median progressionfree survival, disease control frequency, safety assessment, overall survival. Research number: NCT03274882.Results. A total of 26 patients were included in the study; the median age was 60.5 years (30 to 78); 19 (73%) women; and 4 patients with ECOG 0 and 22 – with ECOG 1. All patients were previously treated with the inclusion of oxaliplatin, irinotecan, fluoropyrimidines, 21 (81%) – bevacizumab, 6 (23%) – anti-EGFR antibodies, and 2 (7.7%) – regorafenib. The median for treatment courses was 4 (1–21), 11 (42.3%) patients were treated for 6 months or more. The two-month progression-free survival rate was 52% with a median progreesion-free survival rate of 4 months (95% CI 1.8–7.4 months). The median of total survival rate was 11 months (95% CI 5,2–16,8 months). Disease control was achieved in 60%. Neutropenia, nausea, vomiting, anemia, weakness prevailed among undesirable events associated with treatment (≥5 patients). The majority of complications were of the 1st–2nd degree. Among the undesirable events of the 3rd–4th degree, neutropenia was more common, while in 3 patients febrile neutropenia of the 3rd degree was registered.Conclusions. In the Russian population of patients with colorectal chemorefractory cancer, the drug FTD/TPI (TAS-102) shows efficacy and tolerability comparable to the RECOURSE registration study