MD654Z - Method for predicting the course of II and III stage malignant melanoma - Google Patents

Method for predicting the course of II and III stage malignant melanoma

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MD654Z
MD654Z MDS20120167A MDS20120167A MD654Z MD 654 Z MD654 Z MD 654Z MD S20120167 A MDS20120167 A MD S20120167A MD S20120167 A MDS20120167 A MD S20120167A MD 654 Z MD654 Z MD 654Z
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Moldova
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malignant melanoma
tct
cells
evolution
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MDS20120167A
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Romanian (ro)
Russian (ru)
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Валериу ПАЛАДЕ
Константин ЖУКОВСКИЙ
Виктор ЧЕРНАТ
Георге ЦЫБЫРНЭ
Юлиан ЦУРКАНУ
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Валериу ПАЛАДЕ
Константин ЖУКОВСКИЙ
Виктор ЧЕРНАТ
Георге ЦЫБЫРНЭ
Юлиан ЦУРКАНУ
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Abstract

The invention relates to medicine, particularly to oncology and can be used for predicting the course of II and III stage malignant melanoma.According to the invention, the claimed method involves the clinical and paraclinical examination, where are determined the following parameters: clarification of the stage of disease (ST), presence of ulcer formation (U), tumor cell type (TCT), Clark's level of invasion (NI), tumor thickness under Breslow (GT); applied method of treatment (MT) and sex of the patient (SP), then it is calculated the discriminant function (F) by the formula:F= -6,345 + 1,386 × ST + 4,768 × MT - 2,596 × SP - 3,384 × U + 0,806 × TCT + 1,780 × NI - 1,136 × GT.In the case where F < 0 is predicted a favorable course of malignant melanoma, and when F > 0 - an unfavorable course.

Description

Invenţia se referă la medicină, în special la oncologie şi poate fi utilizată pentru pronosticarea evoluţiei melanomului malign de stadiul II şi III. The invention relates to medicine, especially to oncology and can be used to predict the evolution of stage II and III malignant melanoma.

Depistarea melanomului malign la pacient are impact negativ asupra pronosticării supravieţuirii şi până în prezent poartă un caracter controversat. Creşterea alarmantă a incidenţei, prevalenţei şi mortalităţii a fost documentată de studiile recente. Incidenţa şi rata de deces de melanom malign continuă să crească. În SUA în 2008 au fost înregistrate 62480 cazuri noi de melanom şi 8420 decese. Riscul de dezvoltare a melanomului malign este de 1 la 41 bărbaţi şi 1 la 61 femei ( Jemal A, Siegel R, Ward E, et al. Cancer Statistics, 2008. CCancer J Clin 2008, Nr. 58, p. 71-96). În studiile prospective, unii autori au raportat corelaţia între diferiţi factori de pronostic şi supravieţuirea pacientului cu melanom malign. Cu toate acestea nu au fost efectuate studii care ar fi evaluat pronosticul individual al pacientului cu melanom malign luând în consideraţie mai multe entităţi patologice importante. The detection of malignant melanoma in the patient has a negative impact on the prognosis of survival and is still controversial. The alarming increase in incidence, prevalence and mortality has been documented by recent studies. The incidence and death rate of malignant melanoma continues to rise. In the USA in 2008, 62,480 new cases of melanoma and 8,420 deaths were registered. The risk of developing malignant melanoma is 1 in 41 men and 1 in 61 women ( Jemal A, Siegel R, Ward E, et al. Cancer Statistics, 2008. CCancer J Clin 2008, No. 58, p. 71-96) . In prospective studies, some authors reported the correlation between different prognostic factors and the survival of patients with malignant melanoma. However, no studies have been conducted that would have evaluated the individual prognosis of the patient with malignant melanoma taking into account several important pathological entities.

Balch C.M., Buzaid A.C., Soong S.J. au analizat caracteristicile maladiei, supravieţuirea şi mortalitatea ţinând cont de diferiţi factori. După studii multilaterale au prezentat date de pronostic al melanomului malign în dependenţă de doi factori importanţi ca: stadiul patologiei diagnosticate şi prezenţa sau lipsa ulceraţiei. Pronosticul fiind prezentat sub formă de tabel [1]. Balch C.M., Buzaid A.C., Soong S.J. analyzed disease characteristics, survival and mortality taking into account different factors. After multilateral studies, they presented data on the prognosis of malignant melanoma depending on two important factors such as: the stage of the diagnosed pathology and the presence or absence of ulceration. The prognosis being presented in the form of a table [1].

Stadiul IA IB IIA IIB IIC IIIA IIIB IIIC Neulcerat 95% 89% 79% 67% - 67% 54% 28% Ulcerat - 91% 77% 63% 45% - 52% 24% Stage IA IB IIA IIB IIC IIIA IIIB IIIC Non-ulcerated 95% 89% 79% 67% - 67% 54% 28% Ulcerated - 91% 77% 63% 45% - 52% 24%

Montanara S., Luaschi A. şi Fedeli P. în 2005 au analizat caracteristicile maladiei, supravieţuirea şi mortalitatea în funcţie de diferiţi factori, inclusiv stadiul maladiei, grosimea tumorii primare după Breslow, ulceraţia tumorii, nivelul de invazie a tumorii după Clark. Supravieţuirea a fost estimată utilizând metoda curbelor Kaplan-Meier [2]. Curba de supravieţuire Kaplan-Meier se prezintă sub formă de grafic, unde axa absciselor indică lunile, iar axa ordonatelor procentul pacienţilor supravieţuitori. Montanara S., Luaschi A. and Fedeli P. in 2005 analyzed disease characteristics, survival and mortality according to different factors, including disease stage, primary tumor thickness according to Breslow, tumor ulceration, tumor invasion level according to Clark. Survival was estimated using the Kaplan-Meier curve method [2]. The Kaplan-Meier survival curve is presented as a graph, where the abscissa axis indicates the months, and the ordinate axis the percentage of surviving patients.

Dezavantajul acestor metode constă în faptul că pronosticul bolii s-a efectuat pentru un grup de pacienţi, fiind aplicat pentru fiecare factor de pronostic în parte. Metodele au fost utilizate la general, indicând importanţa fiecărei identităţi patologice în particular. Aceste metode nu permit pronosticarea impactului diagnosticării melanomului malign cutanat în dependenţă de anumiţi factori de risc, pentru un oarecare pacient luat în parte. The disadvantage of these methods lies in the fact that the prognosis of the disease was performed for a group of patients, being applied for each prognostic factor separately. The methods were used in general, indicating the importance of each pathological identity in particular. These methods do not allow predicting the impact of the diagnosis of malignant cutaneous melanoma depending on certain risk factors, for any individual patient.

Matematic problema fiind formalizată se reduce la deducerea unei reguli, unui criteriu de discriminare, în baza analizei datelor a două selecţii (pacienţi care au supravieţuit perioada analizată cu criteriile lor de pronostic şi pacienţi care au decedat de această maladie la fel cu criteriile fiecăruia), care permite a atribui un nou element (pacient nou internat) la una din cele două mulţimi cu o exactitate destul de bună. Folosirea analizei discriminante în studiul datelor statistice despre pacienţii trataţi ne-a permis să deducem funcţia discriminantă propusă mai jos, care reprezintă esenţa metodei de pronosticare. Mathematically, the problem being formalized is reduced to the deduction of a rule, a discrimination criterion, based on the data analysis of two selections (patients who survived the analyzed period with their prognostic criteria and patients who died of this disease with the same criteria of each one), which allows assigning a new element (new hospitalized patient) to one of the two sets with a fairly good accuracy. The use of discriminant analysis in the study of statistical data about treated patients allowed us to derive the discriminant function proposed below, which represents the essence of the forecasting method.

Conform invenţiei, metoda revendicată include examenul clinic şi paraclinic, unde se stabilesc următorii parametri: concretizarea stadiului bolii (ST), prezenţa ulceraţiei (U), tipul celular al tumorii (TCT), nivelul de invazie după Clark (NI), grosimea tumorii după Breslow (GT); metoda de tratament aplicată (MT) şi sexul pacientului (SP), apoi se calculează funcţia discriminantă (F) conform formulei: According to the invention, the claimed method includes the clinical and paraclinical examination, where the following parameters are established: concretization of the stage of the disease (ST), the presence of ulceration (U), the cell type of the tumor (TCT), the level of invasion according to Clark (NI), the thickness of the tumor according Breslow (GT); the applied treatment method (MT) and the patient's gender (SP), then the discriminant function (F) is calculated according to the formula:

F= -6,345 + 1,386 × ST + 4,768 × MT - 2,596 × SP - 3,384 × U + 0,806 × TCT + 1,780 × NI - 1,136 × GT. F= -6.345 + 1.386 × ST + 4.768 × MT - 2.596 × SP - 3.384 × U + 0.806 × TCT + 1.780 × NI - 1.136 × GT.

În cazul în care F < 0 se pronostichează o evoluţie favorabilă a melanomului malign, iar când F > 0 - o evoluţie nefavorabilă. If F < 0, a favorable evolution of malignant melanoma is predicted, and when F > 0 - an unfavorable evolution.

Rezultatul constă în creşterea exacticităţii pronosticării evoluţiei nefavorabile a melanomului malign, datorită utilizării în metoda dată a parametrilor clinici şi paraclinici. The result consists in increasing the accuracy of predicting the unfavorable evolution of malignant melanoma, due to the use of clinical and paraclinical parameters in the given method.

Avantajul constă în sporirea exactităţii şi a obiectivizării pronosticării evoluţiei nefavorabile sau favorabile la pacienţii cu melanom malign în primul an după diagnosticarea maladiei. Metoda propusă permite depistarea precoce a bolnavilor cu risc sporit de agravare, fapt ce impune o atenţie mai mare pentru această categorie de pacienţi cu corijarea la timp a programului terapeutic. The advantage consists in increasing the accuracy and objectification of predicting the unfavorable or favorable evolution in patients with malignant melanoma in the first year after the diagnosis of the disease. The proposed method allows the early detection of patients with increased risk of worsening, a fact that requires greater attention for this category of patients with timely correction of the therapeutic program.

Metoda de pronosticare a evoluţiei melanomului malign de stadiul II şi III se efectuează în felul următor: se efectuează examenul clinic şi paraclinic, unde se stabilesc următorii parametri: concretizarea stadiului bolii (ST), prezenţa ulceraţiei (U), tipul celular al tumorii (TCT), nivelul de invazie după Clark (NI), grosimea tumorii după Breslow (GT); metoda de tratament aplicată (MT) şi sexul pacientului (SP), apoi se calculează funcţia discriminantă (F) conform formulei: The method of prognosticating the evolution of stage II and III malignant melanoma is carried out in the following way: the clinical and paraclinical examination is performed, where the following parameters are established: the concretization of the stage of the disease (ST), the presence of ulceration (U), the cell type of the tumor (TCT ), invasion level according to Clark (NI), tumor thickness according to Breslow (GT); the applied treatment method (MT) and the patient's gender (SP), then the discriminant function (F) is calculated according to the formula:

F= -6,345 + 1,386 × ST + 4,768 × MT - 2,596 × SP - 3,384 × U + 0,806 × TCT + 1,780 × NI - 1,136 × GT, F= -6.345 + 1.386 × ST + 4.768 × MT - 2.596 × SP - 3.384 × U + 0.806 × TCT + 1.780 × NI - 1.136 × GT,

unde parametrii menţionaţi primesc următoarele valori: where the mentioned parameters receive the following values:

ST 1 - IIa 2 - IIb 3 - IIc 4 - IIIa 5 - IIIb 6 - IIIc MT 1 - crioexcizie 2 - excizie SP 1 - bărbat 2 - femeie U 0 - lipsă 1 - prezentă TCT 1 - celule epiteliale 2 - celule fuziforme 3 - celule mixte 4 - celule nevice 5 - celule melanocite de tip lentigo NI 1 - nivelul I 2 - nivelul II 3 - nivelul III 4 - nivelul IV 5 - nivelul V GT grosimea tumorii, mm ST 1 - IIa 2 - IIb 3 - IIc 4 - IIIa 5 - IIIb 6 - IIIc MT 1 - cryoexcision 2 - SP excision 1 - male 2 - female U 0 - absent 1 - present TCT 1 - epithelial cells 2 - fusiform cells 3 - mixed cells 4 - nevi cells 5 - lentigo-type melanocyte cells NI 1 - level I 2 - level II 3 - level III 4 - level IV 5 - level V GT tumor thickness, mm

şi în cazul în care F < 0 se pronostichează o evoluţie favorabilă a melanomului malign, iar când F > 0 - o evoluţie nefavorabilă. and if F < 0, a favorable evolution of malignant melanoma is predicted, and when F > 0 - an unfavorable evolution.

Verificarea funcţiei discriminante s-a efectuat la un lot de 26 pacienţi cu diagnosticul - melanom malign cutanat cu diferite localizări pe parcursul unui an. Rezultatul favorabil a fost considerat în cazul în care F < 0. The verification of the discriminant function was carried out in a group of 26 patients with the diagnosis - cutaneous malignant melanoma with different locations during one year. The favorable result was considered if F < 0.

Rezultatul real Rezultatul aşteptat Favorabil Nefavorabil Total Favorabil, persoane (%) 5 (83,33%) 1(16,67%) 6(100%) Nefavorabil, persoane (%) 2 (10%) 18(90%) 20(100%) Total, persoane (%) 7(26,92%) 19(73,08%) 26(100%) Actual result Expected result Favorable Unfavorable Total Favorable, persons (%) 5 (83.33%) 1(16.67%) 6(100%) Unfavorable, persons (%) 2 (10%) 18(90%) 20( 100%) Total, people (%) 7(26.92%) 19(73.08%) 26(100%)

Drept indicaţie pentru utilizarea acestei metode constituie depistarea pacienţilor cu risc sporit de evoluţie nefavorabilă a maladiei în primele 12 luni în scopul întocmirii unei tactici precoce de tratament. As an indication for the use of this method, it is the detection of patients with an increased risk of unfavorable evolution of the disease in the first 12 months in order to draw up an early treatment strategy.

Contraindicaţii pentru utilizarea acestei metode nu sunt. There are no contraindications for using this method.

Exemple concrete de realizare Concrete examples of realization

Exemplul 1 Example 1

Pacientul Ş., 77 ani, la internare - melanom malign al pielii obrazului drept. S-au înregistrat următoarele rezultate: ST - IIc - 3; MT - metoda de tratament aplicată: crioelectroexcizie - 1; SP - Genul: M - 1; U - ulceraţia: da - 1; TCT - mixte - 3; NI - nivel de ivazie Clark: III - 3; GT - grosimea tumorii Breslow: (mm): 4,0. Valoarea calculată a funcţiei discriminante F = -1,321, adică F < 0, fapt care permite pronosticarea la acest pacient a unei evoluţii favorabile a maladiei, ceea ce demonstrează coincidenţa pronosticului cu rezultatul clinic favorabil. Patient Ş., 77 years old, admitted - malignant melanoma of the skin of the right cheek. The following results were recorded: ST - IIc - 3; MT - applied treatment method: cryoelectroexcision - 1; SP - Gender: M - 1; U - ulceration: yes - 1; TCT - mixed - 3; NI - Clark invasion level: III - 3; GT - Breslow tumor thickness: (mm): 4.0. The calculated value of the discriminant function F = -1.321, i.e. F < 0, which allows the prognosis for this patient of a favorable evolution of the disease, which demonstrates the coincidence of the prognosis with the favorable clinical outcome.

Exemplul 2 Example 2

Pacientul B., 51 ani, s-a internat cu diagnosticul: melanom malign al pielii regiunii temporale. A fost aplicată metoda propusă de cercetare. S-au obţinut următoarele rezultate: ST-IIIb - 5; MT - metoda de tratament aplicată: excizie - 2; SP - genul: F - 2; U - ulceraţia; da - 1; TCT - nevice - 4; NI - nivelul de ivazie Clark: III - 3; GT - grosimea tumorii Breslow: (mm): 4,0. Patient B., 51 years old, was hospitalized with the diagnosis: malignant melanoma of the skin of the temporal region. The proposed research method was applied. The following results were obtained: ST-IIIb - 5; MT - applied treatment method: excision - 2; SP - gender: F - 2; U - ulceration; yes - 1; TCT - virgins - 4; NI - Clark invasion level: III - 3; GT - Breslow tumor thickness: (mm): 4.0.

Valoarea calculată a funcţiei discriminante F = 4,429, adică F > 0, ceea ce indică o evoluţie nefavorabilă a maladiei. Metoda aplicată a demonstrat coincidenţa pronosticului cu rezultatul real. Pacientul a decedat în primele 12 luni de supraveghere. The calculated value of the discriminant function F = 4.429, i.e. F > 0, which indicates an unfavorable evolution of the disease. The applied method demonstrated the coincidence of the prognosis with the real result. The patient died within the first 12 months of follow-up.

Exemplul 3 Example 3

Pacientul S., 71 ani, s-a internat cu diagnosticul: melanom malign al pielii în regiunea temporală dreaptă. În urma investigaţiilor efectuate s-au obţinut următoarele rezultate: ST - IIc - 3; MT - metoda de tratament aplicată: crioelectroexcizie - 1; SP - genul: M - 1; U - ulceraţia: da - 1; TCT - epiteliale - 1; NI - nivel de ivazie Clark: IV - 4, GT - grosimea tumorii Breslow: (mm): 4,0. Valoarea calculată a funcţiei discriminante F = 0,627, adică F > 0, ceea ce permite pronosticarea unei evoluţii nefavorabile a maladiei. În realitate după 12 luni de medicaţie s-a observat o ameliorare evidentă a stării pacientului. Ulterior pacientul a fost supravegheat timp de 18 luni fără date de progresare a maladiei. Patient S., 71 years old, was hospitalized with the diagnosis: malignant melanoma of the skin in the right temporal region. Following the investigations, the following results were obtained: ST - IIc - 3; MT - applied treatment method: cryoelectroexcision - 1; SP - gender: M - 1; U - ulceration: yes - 1; TCT - epithelial - 1; NI - Clark invasion level: IV - 4, GT - Breslow tumor thickness: (mm): 4.0. The calculated value of the discriminant function F = 0.627, i.e. F > 0, which allows predicting an unfavorable evolution of the disease. In reality, after 12 months of medication, an obvious improvement in the patient's condition was observed. Subsequently, the patient was monitored for 18 months without data on disease progression.

Având la bază datele obţinute pe parcursul unui an de supraveghere a pacienţilor cu melanom malign cutanat, putem conclude că metoda propusă de pronosticare a evoluţiei permite depistarea precoce a bolnavilor cu risc sporit de agravare, fapt ce impune o mai mare atenţie pentru această categorie de pacienţi cu corijarea la timp a programului terapeutic. Based on the data obtained during one year of surveillance of patients with cutaneous malignant melanoma, we can conclude that the proposed method of prognosticating the evolution allows the early detection of patients with an increased risk of worsening, a fact that requires greater attention for this category of patients with timely correction of the therapeutic program.

1. Balch C. M., Buzaid A. C., Soong S. J., et al. Final version of the American Joint Committee on Cancer stagind system for cutaneous melanoma. J. Clin. Oncol., 2001, vol. 19, p. 3635-3648 1. Balch C.M., Buzaid A.C., Soong S.J., et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J. Clin. Oncol., 2001, vol. 19, pp. 3635-3648

2. Montanara S., Luaschi A., Fideli P. et al. Malignat melanoma: analysis of survey, Ann. Oncol., 2005, 15(2S), p. 81-83 2. Montanara S., Luaschi A., Fideli P. et al. Malignant melanoma: analysis of survey, Ann. Oncol., 2005, 15(2S), pp. 81-83

Claims (1)

Metodă de pronosticare a evoluţiei melanomului malign de stadiul II şi III, care constă în aceea că se efectuează examenul clinic şi paraclinic, unde se stabilesc următorii parametri: concretizarea stadiului bolii (ST), prezenţa ulceraţiei (U), tipul celular al tumorii (TCT), nivelul de invazie după Clark (NI), grosimea tumorii după Breslow (GT); metoda de tratament aplicată (MT) şi sexul pacientului (SP), apoi se calculează funcţia discriminantă (F) conform formulei: F= -6,345 + 1,386 × ST + 4,768 × MT - 2,596 × SP - 3,384 × U + 0,806 × TCT + 1,780 × NI - 1,136 × GT, unde parametrii menţionaţi primesc următoarele valori:Method for predicting the evolution of stage II and III malignant melanoma, which consists in carrying out the clinical and paraclinical examination, where the following parameters are established: concretization of the stage of the disease (ST), the presence of ulceration (U), the cell type of the tumor (TCT ), invasion level according to Clark (NI), tumor thickness according to Breslow (GT); the applied treatment method (MT) and the patient's gender (SP), then the discriminant function (F) is calculated according to the formula: F= -6.345 + 1.386 × ST + 4.768 × MT - 2.596 × SP - 3.384 × U + 0.806 × TCT + 1.780 × NI - 1.136 × GT, where the mentioned parameters receive the following values: ST 1 - IIa 2 - IIb 3 - IIc 4 - IIIa 5 - IIIb 6 - IIIc MT 1 - crioexcizie 2 - excizie SP 1 - bărbat 2 - femeie U 0 - lipsă 1 - prezentă TCT 1 - celule epiteliale 2 - celule fuziforme 3 - celule mixte 4 - celule nevice 5 - celule melanocite de tip lentigo NI 1 - nivelul I 2 - nivelul II 3 - nivelul III 4 - nivelul IV 5 - nivelul V GT grosimea tumorii, mm şi în cazul în care F < 0 se pronostichează o evoluţie favorabilă a melanomului malign, iar când F > 0 - o evoluţie nefavorabilă. ST 1 - IIa 2 - IIb 3 - IIc 4 - IIIa 5 - IIIb 6 - IIIc MT 1 - cryoexcision 2 - SP excision 1 - male 2 - female U 0 - absent 1 - present TCT 1 - epithelial cells 2 - fusiform cells 3 - mixed cells 4 - nevi cells 5 - lentigo-type melanocyte cells NI 1 - level I 2 - level II 3 - level III 4 - level IV 5 - level V GT tumor thickness, mm and if F < 0, a favorable evolution of malignant melanoma is predicted, and when F > 0 - an unfavorable evolution.
MDS20120167A 2012-11-20 2012-11-20 Method for predicting the course of II and III stage malignant melanoma MD654Z (en)

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MD239Z (en) * 2010-02-15 2011-02-28 Государственный Медицинский И Фармацевтический Университет "Nicolae Testemitanu" Республики Молдова Method of predicting the clinical development of I stage breast cancer
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MD239Z (en) * 2010-02-15 2011-02-28 Государственный Медицинский И Фармацевтический Университет "Nicolae Testemitanu" Республики Молдова Method of predicting the clinical development of I stage breast cancer

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Title
Balch C. M., Buzaid A. C., Soong S. J., et al. Final version of the American Joint Committee on Cancer stagind system for cutaneous melanoma. J. Clin. Oncol., 2001, vol. 19, p. 3635-3648 *
Montanara S., Luaschi A., Fideli P. et al. Malignat melanoma: analysis of survey, Ann. Oncol., 2005, 15(2S), p. 81-83 *

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