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NEOADJUVANT  PHOTODYNAMIC  THERAPY  IN  THE  SURGICAL  TREATMENT  OF  PATIENTS  WITH CUTANEOUS  MELANOMA
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NEOADJUVANT PHOTODYNAMIC THERAPY IN THE SURGICAL TREATMENT OF PATIENTS WITH CUTANEOUS MELANOMA

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M.Y. Myasnyankin

M.Y. Myasnyankin
NEOADJUVANT PHOTODYNAMIC THERAPY IN THE SURGICAL TREATMENT OF PATIENTS WITH CUTANEOUS MELANOMA

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NEOADJUVANT  PHOTODYNAMIC  THERAPY  IN  THE  SURGICAL  TREATMENT  OF  PATIENTS  WITH CUTANEOUS  MELANOMA NEOADJUVANT PHOTODYNAMIC THERAPY IN THE SURGICAL TREATMENT OF PATIENTS WITH CUTANEOUS MELANOMA Presentation Transcript

  • N. N. Petrov Oncology Scientific-research InstituteN. N. Petrov Oncology Scientific-research InstituteI.I. Mechnikov Northwest State Medical UniversityI.I. Mechnikov Northwest State Medical UniversityNEOADJUVANT PHOTODYNAMIC THERAPY IN THENEOADJUVANT PHOTODYNAMIC THERAPY IN THESURGICAL TREATMENT OF PATIENTS WITHSURGICAL TREATMENT OF PATIENTS WITHCUTANEOUS MELANOMACUTANEOUS MELANOMA  Moscow 2013Moscow 2013Head:M.D., Professor G. I. GaftonRapporteur:M.Y. Myasnyankin
  • BackgroundBackground The significant increase in the morbidity rate of theThe significant increase in the morbidity rate of thepopulation of melanoma of the skin, as well as thepopulation of melanoma of the skin, as well as thedelay in the diagnosis of primary tumor dictates thedelay in the diagnosis of primary tumor dictates theneed to develop new methods of systemneed to develop new methods of systemneoadjuvant the treatment of patients.neoadjuvant the treatment of patients. In this respect, a promising, it is the use ofIn this respect, a promising, it is the use ofneoadjuvant photodynamic therapy (PDT) inneoadjuvant photodynamic therapy (PDT) inpatients with melanoma of the skin.patients with melanoma of the skin.
  • AimAim To study of the impact of neoadjuvant PDT onTo study of the impact of neoadjuvant PDT onthe indices of T - and B-cellar immune answer inthe indices of T - and B-cellar immune answer inthe surgical treatment of patients with melanomathe surgical treatment of patients with melanomaof the skin of the I-III stage.of the skin of the I-III stage.
  • Objectives of the studyObjectives of the study To study the induction of apoptosis melanomaTo study the induction of apoptosis melanomacells of human skin under the influence of PDTcells of human skin under the influence of PDTin the experiment in vitroin the experiment in vitro Evaluate the impact of operations with orEvaluate the impact of operations with orwithout PDT on the immunocompetent cells ofwithout PDT on the immunocompetent cells ofperipheral blood in patients with localizedperipheral blood in patients with localizedmelanoma skinmelanoma skin
  • Scientific innovationScientific innovationIn this workIn this work :: developed an original technique of neoadjuvant PDT indeveloped an original technique of neoadjuvant PDT inthe treatment of localized cutaneous melanomathe treatment of localized cutaneous melanoma(prepared by the application for an invention)(prepared by the application for an invention) explore various modes of FD-effects of usingexplore various modes of FD-effects of usingphotoditazini in experiments in vitrophotoditazini in experiments in vitro studied immunological parameters in patients withstudied immunological parameters in patients withlocalized form of melanoma of the skin, receivinglocalized form of melanoma of the skin, receivingneoadjuvant photodynamic therapy and surgicalneoadjuvant photodynamic therapy and surgicaltreatmenttreatment
  • Research designResearch designIn accordance with the objectives of the research,In accordance with the objectives of the research,the work was divided into two parts:the work was divided into two parts:experimentalexperimental andand clinicalclinical
  • Method of experimental studiesMethod of experimental studies For experimental in vitro studies using a cellularFor experimental in vitro studies using a cellularline melanoma of a skin of the person (Mel 226).line melanoma of a skin of the person (Mel 226).
  • .. The level of apoptosis was assessed by theThe level of apoptosis was assessed by theapoptosis index (AI)apoptosis index (AI)::the number of apoptotic cellsthe number of apoptotic cellsAI = ________________________ х 100%AI = ________________________ х 100%total number of cellstotal number of cells
  • AI considered separately for all the analyzed cells:AI considered separately for all the analyzed cells:  cells with a green staining, which are at the stage of earlycells with a green staining, which are at the stage of earlyapoptosis (Annexin+, PI -), (1a);apoptosis (Annexin+, PI -), (1a);cells with double staining (Annexin+, PI+) - late stage ofcells with double staining (Annexin+, PI+) - late stage ofapoptosis (1b)apoptosis (1b)Fig. 1. The cells at the stage of «early» apoptosis (1A) and «late» apoptosis (1B)Fig. 1. The cells at the stage of «early» apoptosis (1A) and «late» apoptosis (1B)а b
  • Methodology of clinical studiesMethodology of clinical studies In a clinical study included patients whoIn a clinical study included patients whoreceived treatment in «Oncology researchreceived treatment in «Oncology researchInstitute. N.N. Petrov» of the Ministry of healthInstitute. N.N. Petrov» of the Ministry of healthof Russia from July 2012 and January 2013of Russia from July 2012 and January 2013
  • .. The scheme of the study:The scheme of the study:1)1) Evaluation of IP → Operation → 7 days:Evaluation of IP → Operation → 7 days:evaluation of IPevaluation of IP2)2) Evaluation of IP → PDT → Operation → 7 days:Evaluation of IP → PDT → Operation → 7 days:evaluation of IPevaluation of IP3)3) IP - immune statusIP - immune status
  • Characteristics of patientsCharacteristics of patientsCharacteristicsPathiens Total1 2abs. % (ДИ) abs. % (ДИ) abs. %number of patients 9 16 25 100Ageaverageinterval5439-875334-855634-87menwomen4544(12-77)56(23-88)31319(4-41)81(59-96)71828(10-46)72(54-90)StagiesIIIIII52256 (23-88)22 (3-53)22 (3-53)106063 (39-86)37 (14-61)0 (0-6)158260 (41-79)32 (14-50)8 (1-22)..
  • Methods of statistical processingMethods of statistical processingof the dataof the data For statistical processing of the data usedFor statistical processing of the data usedmethods of descriptive statistics: the calculationmethods of descriptive statistics: the calculationof the 95% confidence interval (CI) for AI andof the 95% confidence interval (CI) for AI andthe criterion of characters Уилкоксона forthe criterion of characters Уилкоксона fordependent observationsdependent observations Calculations have been carried out using theCalculations have been carried out using theSPSS v.17. The study was accepted significanceSPSS v.17. The study was accepted significancelevel p≤0,05level p≤0,05
  • The resultsThe results (1)(1)Fig.2. AI in 1 hour after PD-exposure exposure 6 min. (a) and 10 min. (b):Fig.2. AI in 1 hour after PD-exposure exposure 6 min. (a) and 10 min. (b):the early and the late apoptosisthe early and the late apoptosisа б
  • The resultsThe results (2)(2)Fig.3. AI 4 hours after the PD-exposure exposure 6 min. (a) and 10 min.Fig.3. AI 4 hours after the PD-exposure exposure 6 min. (a) and 10 min.(b): the early and the late apoptosis(b): the early and the late apoptosisа б
  • Evaluation of the undesirableEvaluation of the undesirablephenomena PDTphenomena PDT Of the complications and adverse events inOf the complications and adverse events inpatients receiving neoadjuvant PDT, there was apatients receiving neoadjuvant PDT, there was alocal hyperemia in the «zone illumination»local hyperemia in the «zone illumination»
  • The content of the main subpopulations of lymphocytes in the blood ofThe content of the main subpopulations of lymphocytes in the blood ofpatients with localized melanoma of the skin prior to treatment, and the 7-patients with localized melanoma of the skin prior to treatment, and the 7-th day after operationth day after operationLymphocytic gate Group Before theoperationM±mAfter the operationM±mрCD3+CD19-PDT(-) 1.32±0.16 1.50±0.6 0.036PDT(+) 1.2±0.09 1.3±0.4 0.18CD3+CD4+PDT(-) 0.83±0.1 0.95±0.4 0.092PDT(+) 0.72±0.05 0.91±0.3 0.02CD3+CD8+PDT(-) 0.46±0.09 0.48±0.24 0.263PDT(+) 0.47±0.06 0.47±0.2 0.19CD3+CD4+CD8+PDT(-) 0.02±0.01 0.02±0.02 0.063PDT(+) 0.02±0.01 0.03±0.04 0.75CD3-CD19+PDT(-) 0.18±0.04 0.23±0.1 0.31PDT(+) 0.16±0.01 0.19±0.08 0.02CD3+CD4+HLADR+PDT(-) - - -PDT(+) 0.03±0.004 0.05±0.009 0.05
  • ConclusionsConclusions (1)(1) The increase of concentration of photoditaziniThe increase of concentration of photoditazinidoes not lead to an increase in the number ofdoes not lead to an increase in the number ofcells at early stage of apoptosis (p>0.05).cells at early stage of apoptosis (p>0.05).
  • ConclusionsConclusions (2)(2) The prolonging exposure time leads to increaseThe prolonging exposure time leads to increasein the late forms of apoptosis (p<0.05)in the late forms of apoptosis (p<0.05)
  • Conclusions (3)Conclusions (3) The use of photoditazini in the dose of 50 mgThe use of photoditazini in the dose of 50 mgfollowed by irradiation (662 nm, 400 j) 2 days priorfollowed by irradiation (662 nm, 400 j) 2 days priorto surgical intervention contributes to theto surgical intervention contributes to theactivation of T - and b-cellular link of the immuneactivation of T - and b-cellular link of the immunesystem (p<0.05)system (p<0.05)
  • The main task of any medical practiceThe main task of any medical practiceis the memory of what medicineis the memory of what medicineshould serve the benefit of the sickshould serve the benefit of the sickpeople.people.«Вопросы хирургической«Вопросы хирургическойдеонтологии»деонтологии»Н.Н.Петров, 1956 г.Н.Н.Петров, 1956 г.
  • M.D., Professor G. I. GaftonM.D., Professor G. I. GaftonSenior laboratory assistant of the Department ofSenior laboratory assistant of the Department ofOncologyOncology1976-19811976-19811 University named after academician I. P.1 University named after academician I. P.Pavlova, Leningrad, St. L. TolstoyPavlova, Leningrad, St. L. TolstoyJunior researcherJunior researcher1981-19911981-19911 University named after academician I. P.1 University named after academician I. P.Pavlova, Leningrad, St. L. TolstoyPavlova, Leningrad, St. L. TolstoySenior researchSenior researchofficerofficer1991-20031991-20031 University named after academician I. P.1 University named after academician I. P.Pavlova, Leningrad, St. L. TolstoyPavlova, Leningrad, St. L. TolstoyDepartment headDepartment heada total of Oncology and urologya total of Oncology and urologyfrom 2003 - «scientific research Institute offrom 2003 - «scientific research Institute ofOncology named N.N. Petrov» of the Ministry ofOncology named N.N. Petrov» of the Ministry ofhealth of Russia, St. Petersburg, str. Leningrad,health of Russia, St. Petersburg, str. Leningrad,etc. 68etc. 68