Treatment of large osteosarcoma in children: new approach
Aim - to improve the treatment results of patients with locally advanced osteosarcoma with large volume using neoadjuvant chemotherapy (NACT) (ifosfamide at a dose of 18 g/ml) and planning of organ-conserving surgery by evaluating the state of tumor pseudocapsule. A study group included 46 children...
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
2013
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| Цитувати: | Treatment of large osteosarcoma in children: new approach / V.L. Kobys, V.F. Konovalenko, N.V. Repinа, T.S. Golovko, L.O. Gulak, T.O. Tarasova, E.V. Zaharycheva, O.F. Matyushok // Experimental Oncology. — 2013. — Т. 35, № 2. — С. 105-108. — Бібліогр.: 14 назв. — англ. |
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irk-123456789-1452142019-01-20T01:23:41Z Treatment of large osteosarcoma in children: new approach Kobys, V.L. Konovalenko, V.F. Repinа, N.V. Golovko, T.S. Gulak, L.O. Tarasova, T.O. Zaharycheva, E.V. Matyushok, O.F. Original contributions Aim - to improve the treatment results of patients with locally advanced osteosarcoma with large volume using neoadjuvant chemotherapy (NACT) (ifosfamide at a dose of 18 g/ml) and planning of organ-conserving surgery by evaluating the state of tumor pseudocapsule. A study group included 46 children aged from 7 to 18 years, mean age - 12 years. In 68 % of the patients tumor volume was larger or significantly larger than 200 ml (from 27 to 2400 ml), mean tumor volume was 342 ml. All patients have been examined by X-ray radiography, CT, Doppler ultrasound. Convenient chemotherapy consisted of methotrexate at a dose of 12 g/ml, cisplatin (120 mg/ml) in combination with doxorubicin (75 mg/ml). If such chemotherapy was considered ineffective with the use of an algorithm for determination of chemotherapy efficacy, 2 cycles of chemotherapy with ifosfamide at a dose of 18 g/ml per course have been applied. At the stage of planning of organ-conserving surgery, the state of tumor pseudocapsule was analyzed. In 6 months post-operative chemotherapy was carried out with the use of methotrexate, cisplatin with doxorubicin, ifosfamide at the same doses. Myelotoxicity of ifosfamide treatment at a dose of 18 g/ml is comparable to that of to a course of doxorubicin + cisplatin: the depth of leucopenia was significantly higher (p << 0,05), the duration of agranulocytosis is similar after such therapies. In the study group, 69,6 % patients have reached grade 3 - 4 pathomorphosis. Organ-conserving surgery was performed in 86,9 % of the patients. Local tumor recurrence was registered in 15,2 % patients of the study group. 5-year relapse-free survival was achieved in 62 +- 10 % (p = 0,02), the overall 5-year survival - 76,5 +- 9 % (p = 0,02). Conclusions: introduction of ifosfamide at a dose of 18 g/ml in the treatment scheme of pediatric patients with locally advanced osteosarcoma along with individualization of pre-oper- g/ml in the treatment scheme of pediatric patients with locally advanced osteosarcoma along with individualization of pre-oper- g/ml in the treatment scheme of pediatric patients with locally advanced osteosarcoma along with individualization of pre-oper- ml in the treatment scheme of pediatric patients with locally advanced osteosarcoma along with individualization of pre-oper- in the treatment scheme of pediatric patients with locally advanced osteosarcoma along with individualization of pre-oper- in the treatment scheme of pediatric patients with locally advanced osteosarcoma along with individualization of pre-oper- in the treatment scheme of pediatric patients with locally advanced osteosarcoma along with individualization of pre-oper- osteosarcoma along with individualization of pre-oper along with individualization of pre-operative chemotherapy, pre-oper ative analysis of NACT efficacy and the state of tumor pseudocapsule during planning stage of organconserving surgery significantly improves efficacy of the therapy in patients with large tumor volume. Key Words: osteosarcoma, children, pseudocapsule tumors, tumor volume, chemotherapy. 2013 Article Treatment of large osteosarcoma in children: new approach / V.L. Kobys, V.F. Konovalenko, N.V. Repinа, T.S. Golovko, L.O. Gulak, T.O. Tarasova, E.V. Zaharycheva, O.F. Matyushok // Experimental Oncology. — 2013. — Т. 35, № 2. — С. 105-108. — Бібліогр.: 14 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/145214 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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Digital Library of Periodicals of National Academy of Sciences of Ukraine |
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DSpace DC |
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English |
| topic |
Original contributions Original contributions |
| spellingShingle |
Original contributions Original contributions Kobys, V.L. Konovalenko, V.F. Repinа, N.V. Golovko, T.S. Gulak, L.O. Tarasova, T.O. Zaharycheva, E.V. Matyushok, O.F. Treatment of large osteosarcoma in children: new approach Experimental Oncology |
| description |
Aim - to improve the treatment results of patients with locally advanced osteosarcoma with large volume using neoadjuvant chemotherapy (NACT) (ifosfamide at a dose of 18 g/ml) and planning of organ-conserving surgery by evaluating the state of tumor pseudocapsule. A study group included 46 children aged from 7 to 18 years, mean age - 12 years. In 68 % of the patients tumor volume was larger or significantly larger than 200 ml (from 27 to 2400 ml), mean tumor volume was 342 ml. All patients have been examined by X-ray radiography, CT, Doppler ultrasound. Convenient chemotherapy consisted of methotrexate at a dose of 12 g/ml, cisplatin (120 mg/ml) in combination with doxorubicin (75 mg/ml). If such chemotherapy was considered ineffective with the use of an algorithm for determination of chemotherapy efficacy, 2 cycles of chemotherapy with ifosfamide at a dose of 18 g/ml per course have been applied. At the stage of planning of organ-conserving surgery, the state of tumor pseudocapsule was analyzed. In 6 months post-operative chemotherapy was carried out with the use of methotrexate, cisplatin with doxorubicin, ifosfamide at the same doses. Myelotoxicity of ifosfamide treatment at a dose of 18 g/ml is comparable to that of to a course of doxorubicin + cisplatin: the depth of leucopenia was significantly higher (p << 0,05), the duration of agranulocytosis is similar after such therapies. In the study group, 69,6 % patients have reached grade 3 - 4 pathomorphosis. Organ-conserving surgery was performed in 86,9 % of the patients. Local tumor recurrence was registered in 15,2 % patients of the study group. 5-year relapse-free survival was achieved in 62 +- 10 % (p = 0,02), the overall 5-year survival - 76,5 +- 9 % (p = 0,02). Conclusions: introduction of ifosfamide at a dose of 18 g/ml in the treatment scheme of pediatric patients with locally advanced osteosarcoma along with individualization of pre-oper- g/ml in the treatment scheme of pediatric patients with locally advanced osteosarcoma along with individualization of pre-oper- g/ml in the treatment scheme of pediatric patients with locally advanced osteosarcoma along with individualization of pre-oper- ml in the treatment scheme of pediatric patients with locally advanced osteosarcoma along with individualization of pre-oper- in the treatment scheme of pediatric patients with locally advanced osteosarcoma along with individualization of pre-oper- in the treatment scheme of pediatric patients with locally advanced osteosarcoma along with individualization of pre-oper- in the treatment scheme of pediatric patients with locally advanced osteosarcoma along with individualization of pre-oper- osteosarcoma along with individualization of pre-oper along with individualization of pre-operative chemotherapy, pre-oper ative analysis of NACT efficacy and the state of tumor pseudocapsule during planning stage of organconserving surgery significantly improves efficacy of the therapy in patients with large tumor volume. Key Words: osteosarcoma, children, pseudocapsule tumors, tumor volume, chemotherapy. |
| format |
Article |
| author |
Kobys, V.L. Konovalenko, V.F. Repinа, N.V. Golovko, T.S. Gulak, L.O. Tarasova, T.O. Zaharycheva, E.V. Matyushok, O.F. |
| author_facet |
Kobys, V.L. Konovalenko, V.F. Repinа, N.V. Golovko, T.S. Gulak, L.O. Tarasova, T.O. Zaharycheva, E.V. Matyushok, O.F. |
| author_sort |
Kobys, V.L. |
| title |
Treatment of large osteosarcoma in children: new approach |
| title_short |
Treatment of large osteosarcoma in children: new approach |
| title_full |
Treatment of large osteosarcoma in children: new approach |
| title_fullStr |
Treatment of large osteosarcoma in children: new approach |
| title_full_unstemmed |
Treatment of large osteosarcoma in children: new approach |
| title_sort |
treatment of large osteosarcoma in children: new approach |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| publishDate |
2013 |
| topic_facet |
Original contributions |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/145214 |
| citation_txt |
Treatment of large osteosarcoma in children: new approach / V.L. Kobys, V.F. Konovalenko, N.V. Repinа, T.S. Golovko, L.O. Gulak, T.O. Tarasova, E.V. Zaharycheva, O.F. Matyushok // Experimental Oncology. — 2013. — Т. 35, № 2. — С. 105-108. — Бібліогр.: 14 назв. — англ. |
| series |
Experimental Oncology |
| work_keys_str_mv |
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| first_indexed |
2025-07-10T21:10:35Z |
| last_indexed |
2025-07-10T21:10:35Z |
| _version_ |
1837295821711736832 |
| fulltext |
Experimental Oncology ��� �������� ���� ���ne���� �������� ���� ���ne� ���ne� ���
TREATMENT OF LARGE OSTEOSARCOMA IN CHILDREN:
NEW APPROACH
V.L. Kobys1,*, V.F. Konovalenko2, N.V. Repinа3, T.S. Golovko4,
L.O. Gulak4, T.O. Tarasova4, E.V. Zaharycheva5, O.F. Matyushok1
1Municipal Clinical Oncological Center, Kyiv, Ukraine
2R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology,
National Academy of Sciences of Ukraine, Kyiv, Ukraine
3Ukrainian Children’s Specialized Hospital “OСHMATDET”, Ministry of Health of Ukraine, Kyiv, Ukraine
4National Cancer Institute, Kyiv, Ukraine
5City Children’s Hospital № 7, Kyiv, Ukraine
Aim: To improve the treatment results of patients with locally advanced osteosarcoma with large volume using neoadjuvant chemo-
therapy (NACT) (ifosfamide at a dose of 18 g/ml) and planning of organ-conserving surgery by evaluating the state of tumor pseudo-
capsule. Patients and Methods: A study group included 46 children aged from 7 to 18 years, mean age — 12 years. In 68% of the
patients tumor volume was larger or significantly larger than 200 ml (from 27 to 2400 ml), mean tumor volume was 342 ml. All patients
have been examined by X-ray radiography, CT, Doppler ultrasound. Convenient chemotherapy consisted of methotrexate at a dose
of 12 g/ml, cisplatin (120 mg/ml) in combination with doxorubicin (75 mg/ml). If such chemotherapy was considered ineffective with
the use of an algorithm for determination of chemotherapy efficacy, 2 cycles of chemotherapy with ifosfamide at a dose of 18 g/ml per
course have been applied. At the stage of planning of organ-conserving surgery, the state of tumor pseudocapsule was analyzed.
In 6 months post-operative chemotherapy was carried out with the use of methotrexate, cisplatin with doxorubicin, ifosfamide at the
same doses. Results: Myelotoxicity of ifosfamide treatment at a dose of 18 g/ml is comparable to that of to a course of doxorubicin +
cisplatin: the depth of leucopenia was significantly higher (p < 0.05), the duration of agranulocytosis is similar after such therapies.
In the study group, 69.6% patients have reached grade 3–4 pathomorphosis. Organ-conserving surgery was performed in 86.9%
of the patients. Local tumor recurrence was registered in 15.2% patients of the study group. 5-year relapse-free survival was achieved
in 62 ± 10% (p = 0.02), the overall 5-year survival — 76.5 ± 9% (p = 0.02). Conclusions: Introduction of ifosfamide at a dose
of 18 g/ml in the treatment scheme of pediatric patients with locally advanced osteosarcoma along with individualization of pre-oper- 18 g/ml in the treatment scheme of pediatric patients with locally advanced osteosarcoma along with individualization of pre-oper-g/ml in the treatment scheme of pediatric patients with locally advanced osteosarcoma along with individualization of pre-oper-/ml in the treatment scheme of pediatric patients with locally advanced osteosarcoma along with individualization of pre-oper-ml in the treatment scheme of pediatric patients with locally advanced osteosarcoma along with individualization of pre-oper- in the treatment scheme of pediatric patients with locally advanced osteosarcoma along with individualization of pre-oper-in the treatment scheme of pediatric patients with locally advanced osteosarcoma along with individualization of pre-oper-osteosarcoma along with individualization of pre-oper- along with individualization of pre-oper-
ative chemotherapy, pre-operative analysis of NACT efficacy and the state of tumor pseudocapsule during planning stage of organ-
conserving surgery significantly improves efficacy of the therapy in patients with large tumor volume.
Key Words: osteosarcoma, children, pseudocapsule tumors, tumor volume, chemotherapy.
Up to date the treatment efficacy for patients with
locally advanced osteosarcoma with large t�mor vol�osteosarcoma with large t�mor vol�with large t�mor vol�
�me �> ��� ml� remains low compared to standard risk
patients. For example� according to the data of Bielack
et al. [�]� 4 year s�rvival of s�ch patients was 4�% while
in standard risk gro�p � year s�rvival yielded 76% [�].
It has been shown that in the cases when t�mor vol�me
is larger than ��� ml� microscopic metastatic t�mor
emboli are already fo�nd in l�ngs and bone marrow [�].
Performance of organ�conserving s�rgery is contrain� of organ�conserving s�rgery is contrain�of organ�conserving s�rgery is contrain� organ�conserving s�rgery is contrain�organ�conserving s�rgery is contrain��conserving s�rgery is contrain�conserving s�rgery is contrain� s�rgery is contrain�s�rgery is contrain� is contrain�is contrain� contrain�contrain�
dicated �pon massive m�scle inj�ry [4] or significantly
advanced soft tiss�e component ��p to 6 cm� or t�mor
vol�me larger than ��� ml [4]. Picci et al. [�] have revealed
a significant dependence of development of local t�mor
rec�rrence on s�rgical p�rity of t�mor resection margins
�pon s�rgical treatment. At the same time Li et al. [6]
have shown that the development of local rec�rrence did
not differ between the cases of wide margin resection
�> � cm� and close margin resection �from � to � mm from
t�mor edge�. T�mor pse�docaps�le is an anatomic
str�ct�re which separates t�mor and healthy tiss�es
[7]. Presently its pre�s�rgical determination with the �se
of radiological methods is still problematic. By �T it is pos� radiological methods is still problematic. By �T it is pos�radiological methods is still problematic. By �T it is pos� is still problematic. By �T it is pos�is still problematic. By �T it is pos�. By �T it is pos�By �T it is pos� �T it is pos��T it is pos� it is pos�it is pos� is pos�is pos� pos�pos�
sible to determine j�st an ossification of margin zone “soft
tiss�e�t�mor” [�]. With the �se of contrast MRT there
co�ld be determined a margin between the t�mor and
soft tiss�es� b�t it co�ldn’t be strictly differentiated with
perit�moral swelling [9� ��]. Therefore� �p to date d�ring
planning of operation the s�rgeons do not consider the
state of pse�docaps�le [��. ��]. No p�blications abo�t
organ conserving treatment of children with osteosar� conserving treatment of children with osteosar�conserving treatment of children with osteosar� treatment of children with osteosar�treatment of children with osteosar� of children with osteosar�of children with osteosar� children with osteosar�children with osteosar� with osteosar�with osteosar� osteosar�osteosar�
coma consider an importance of t�mor pse�docaps�le
identification for s�rgical planning.
Better res�lts of osteosarcoma treatment directly
depend on efficacy of chemotherapy and improve
s�rvival indexes [��] and decrease the rates of local
t�mor rec�rrence [6].
Rosen et al. [�4] have s�pposed that one of the
methods for improvement of osteosarcoma treatment
res�lts co�ld be the �se of new at the moment prepara� co�ld be the �se of new at the moment prepara�co�ld be the �se of new at the moment prepara� be the �se of new at the moment prepara�be the �se of new at the moment prepara� the �se of new at the moment prepara�the �se of new at the moment prepara� �se of new at the moment prepara��se of new at the moment prepara� of new at the moment prepara�of new at the moment prepara� new at the moment prepara�new at the moment prepara� prepara�prepara�
tion ifosfamide at high doses �from �� to �� g/mІ� and
have revealed a direct dependence between prepara�
tion dose and efficacy.
In modern literat�re there is no information on the �se
of ifosfamide at high dose ��� g/mІ� for treatment of chil� ifosfamide at high dose ��� g/mІ� for treatment of chil�at high dose ��� g/mІ� for treatment of chil� high dose ��� g/mІ� for treatment of chil�high dose ��� g/mІ� for treatment of chil� dose ��� g/mІ� for treatment of chil�dose ��� g/mІ� for treatment of chil� ��� g/mІ� for treatment of chil�g/mІ� for treatment of chil�/mІ� for treatment of chil�mІ� for treatment of chil�І� for treatment of chil�for treatment of chil�
dren with osteosarcoma. D�ring last �� years in foreign
and native literat�re there have been p�blished no res�lts
abo�t individ�alization of preoperative chemotherapy
Received: March 27, 2013.
*Correspondence: E-mail: vadym_kobys@mail.ru
Abbreviations used: NACT — neoadjuvant chemotherapy; PCT —
polychemotherapy.
Exp Oncol ����
��� �� �������
��6 Experimental Oncology ��� �������� ���� ���ne�
with the �se of radiological methods for eval�ation of its
efficacy.
The aim of this work was an improvement of treat�
ment efficacy of children with osteosarcoma.
MATERIALS AND METHODS
In the st�dy there have been analyzed clinical records
of 46 children from 7 to �� years old who �nderwent
the treatment in the Department of Pediatric Oncology
of Instit�te of Oncology �presently — National �ancer
Instit�te� Kyiv� Ukraine� in �999����6� electronic data
base which incl�ded USD�images� �T and MRT medical
comments� and the res�lts of histological st�dy of me�
dicinal t�mor pathomorphism. The protocol № �6 from
��.�9.���9 of �ommittee on Ethics of National �ancer
Instit�te — the work does not violate ethic principles.
Age and gender distrib�tion of children is presented
in Table �. �6 patients �7�%� were from �� to �6 years
old. There was eq�al n�mber of girls and boys.
Table 1. Distribution of children with osteogenic sarcoma by age and gender
Patient’s age, years Gender
7–8 9–10 11–12 13–14 15–16 17–18 Male Female
Number of pa-
tients, n
2 7 11 10 15 1 23 23
Distrib�tion of the patients by t�mor localization
is shown in Table �. In he majority of cases malignant
t�mor was localized in femoral bone �6�.�%� or in shin
bone ��4%�.
Table 2. Localization of tumor in children with osteogenic sarcoma
Localization of tumor in bones
TotalFemoral
bone
Hume-
rus
Fibular
bone
Shin
bone
Radial
bone
Number of pa-
tients, n
28 2 4 11 1 46
Initial t�mor vol�me was determined by �T data.
In �� patients �6�.�%� it was larger or significantly
larger than ��� ml. Mean t�mor vol�me was �4� ml.
In �999 we have developed a treatment protocol
for pediatric osteosarcoma patients “UNDIOR�99”.
It incl�ded the �se of preoperative chemotherapy
�neoadj�vant chemotherapy — NA�T�� analysis of effi�neoadj�vant chemotherapy — NA�T�� analysis of effi��� analysis of effi�� analysis of effi� of effi�of effi�
cacy of administered preparations� and post�operative
chemotherapy dependent on an acq�ired medicinal
t�mor pathomorphism. The scheme of chemotherapy
is presented on Fig. � and �.
Р Effective
PCT Р
Ev
al
ua
tio
n
of
c
he
m
ot
he
ra
py
ef
fic
ac
y
Su
rg
er
yМ М
А
М М А
Ifo Ifo
Ineffective
PCT
1 2 3 4 5 6 7 8 9 10 11
Weeks
Fig. 1. “UNDIOR�99” Preoperative chemotherapy. Notes: М —
methotrexate� �� g/m²; А — dox�ribicin� 7� mg/m²; Р — cisplatin�
��� mg/m²; Ifo — ifosfamide� �� g/m².
As it is shown on Fig. �� in all patients the therapy be� it is shown on Fig. �� in all patients the therapy be�it is shown on Fig. �� in all patients the therapy be� is shown on Fig. �� in all patients the therapy be�is shown on Fig. �� in all patients the therapy be� shown on Fig. �� in all patients the therapy be�shown on Fig. �� in all patients the therapy be� on Fig. �� in all patients the therapy be�on Fig. �� in all patients the therapy be� Fig. �� in all patients the therapy be�Fig. �� in all patients the therapy be�. �� in all patients the therapy be�in all patients the therapy be� all patients the therapy be�all patients the therapy be� patients the therapy be�patients the therapy be� the therapy be�the therapy be� therapy be�therapy be� be�be�
gins from do�ble co�rse of high�dose methotrexate with
7 days interval. Fo�rteen days later chemotherapy is con�. Fo�rteen days later chemotherapy is con�Fo�rteen days later chemotherapy is con� days later chemotherapy is con�days later chemotherapy is con� later chemotherapy is con�later chemotherapy is con� chemotherapy is con�chemotherapy is con� is con�is con� con�con�
tin�ed with intraveno�s bol�s administration of cisplatin
combined with doxor�bicin. At �th week of treatment
�in � weeks after cisplatin + doxor�bicin co�rse� there
is performed an analysis of treatment effectiveness by the
developed algorithm for P�T efficacy determination.
Line of chemotherapy for patients with pathomorphosis
of III–IV degree
ММ Р ММ Р ММ Р ММ Р
Line of chemotherapy for patients with pathomorphosis
of I–II degree
ММ Р ММ Ifo ММ Р ММ Ifo
12 14 16 18 20 22 24 26 28 30 32 34 36 Weeks
Fig. 2. “UNDIOR�99” Postoperative chemotherapy. Notes:
М — methotrexate� �� g/m²; А — doxor�bicin� 7� mg/m²; Р —
cisplatin� ��� mg/m²; Ifo — ifosfamide� �� g/m².
Upon establishment of efficacy of performed
chemotherapy in each individ�al patient� chemotherapy
regimen remains �nchanged� and the patient receives
the second eq�al co�rse: do�ble methotrexate�
cisplatin with doxor�bicin. In the case if performed
therapy is considered ineffective� chemotherapy line
is switched to do�ble co�rse of high�dose ifosfamide
with � week interval. Upon t�mor pathomorphism of ΙΙΙ�
ΙV grades� post�operative chemotherapy has been
performed witho�t replacement of chemoprepara� witho�t replacement of chemoprepara�witho�t replacement of chemoprepara� replacement of chemoprepara�replacement of chemoprepara� of chemoprepara�of chemoprepara� chemoprepara�chemoprepara�
tions� �pon t�mor pathomorphism of Ι�ΙΙ grades — with
addition of high�dose ifosfamide �Fig. ��.
Statistical analysis of the data was done with the
�se of comp�ter program Statistica 6.� �Statsoft Inc�
USA�: comparison of independent variables was per��: comparison of independent variables was per�comparison of independent variables was per� of independent variables was per�of independent variables was per� independent variables was per�independent variables was per� variables was per�variables was per� was per�was per� per�per�
formed by t�criterion for independent variables� analy� by t�criterion for independent variables� analy�by t�criterion for independent variables� analy� t�criterion for independent variables� analy�t�criterion for independent variables� analy��criterion for independent variables� analy�criterion for independent variables� analy� for independent variables� analy�for independent variables� analy� independent variables� analy�independent variables� analy� variables� analy�variables� analy�� analy�analy�
sis of patient’s s�rvival — by Kaplan — Meyer c�rves.
RESULTS AND DISCUSSION
An efficacy of P�T co�rse was determined by the
developed algorithm for determination of NA�T ef� algorithm for determination of NA�T ef�algorithm for determination of NA�T ef� for determination of NA�T ef�for determination of NA�T ef� determination of NA�T ef�determination of NA�T ef� of NA�T ef�of NA�T ef� NA�T ef�NA�T ef� ef�ef�
ficacy via analysis of patient’s t�mor state. This
algorithm incl�des a complex of methods: clinical
and X�ray methods� the data of �T� MRT� USVD. With
the �se of USVD the str�ct�re and vasc�larization
of t�mor soft tiss�e component were examined. Fig.
� demonstrates an initial scan of patient’s t�mor and
its scheme prior to chemotherapy. On Fig. 4 one may
see the scan of the t�mor of the same patient and its
scheme after performed preoperative chemotherapy.
There has been determined a significant decrease
of neomicrovessel n�mbers in t�mor mass and pe� neomicrovessel n�mbers in t�mor mass and pe�neomicrovessel n�mbers in t�mor mass and pe� n�mbers in t�mor mass and pe�n�mbers in t�mor mass and pe� in t�mor mass and pe�in t�mor mass and pe� t�mor mass and pe�t�mor mass and pe� mass and pe�mass and pe� and pe�and pe� pe�pe�
riphery� and formation of t�mor pse�docaps�le co�ld
be observed.
Fig. 3. Scanogram of patient М. prior to chemotherapy. Ap� of patient М. prior to chemotherapy. Ap�of patient М. prior to chemotherapy. Ap� patient М. prior to chemotherapy. Ap�patient М. prior to chemotherapy. Ap� М. prior to chemotherapy. Ap�prior to chemotherapy. Ap� chemotherapy. Ap�Ap�
proximately one h�ndred microvessels are chaotically placed
in t�mor mass and periphery� t�mor soft tiss�e component is not
separated from m�scles.
Experimental Oncology ��� �������� ���� ���ne���� �������� ���� ���ne� ���ne� ��7
Fig. 4. Scanogram of patient М. after preoperative chemotherapy.
Single microvessels in t�mor mass and periphery are vis�alized.
Pse�docaps�le of t�mor co�ld be seen �shown by arrow�. Posi�se�docaps�le of t�mor co�ld be seen �shown by arrow�. Posi� of t�mor co�ld be seen �shown by arrow�. Posi� t�mor co�ld be seen �shown by arrow�. Posi� co�ld be seen �shown by arrow�. Posi� �shown by arrow�. Posi�shown by arrow�. Posi��. Posi�Posi�
tive effect of NA�T
By the data of algorithm for determination of P�T
efficacy� effectiveness of chemotherapy co�rse
was established only in 7 ���.�%� patients� so f�r� 7 ���.�%� patients� so f�r�.�%� patients� so f�r��%� patients� so f�r�so f�r�
ther change of chemopreparation was not req�ired.
In � patient an eval�ation of treatment efficacy was not
performed beca�se of p�r�lent process in the wo�nd.
In other �� patients negative effect of performed
chemotherapy has been registered. After therapy
line switch� d�ring pre�operative combined examina� switch� d�ring pre�operative combined examina�switch� d�ring pre�operative combined examina�� d�ring pre�operative combined examina�d�ring pre�operative combined examina� pre�operative combined examina�pre�operative combined examina� combined examina�combined examina� examina�examina�
tion� chemotherapy effectiveness was doc�mented
in �6 �9�%� from �� patients and P�T efficacy in all
7 patients treated witho�t switch of chemopreparation.
In total� by the data of pre�operative combined exami� total� by the data of pre�operative combined exami�total� by the data of pre�operative combined exami�� by the data of pre�operative combined exami�by the data of pre�operative combined exami� the data of pre�operative combined exami�the data of pre�operative combined exami� data of pre�operative combined exami�data of pre�operative combined exami� of pre�operative combined exami�of pre�operative combined exami� pre�operative combined exami�pre�operative combined exami� combined exami�combined exami� exami�exami�
nation� chemotherapy was effective in 9�.�% of the
patients. By the data of medicinal pathomorphism�
an expressed degree �III�IV by Havos� was registered
only in �� patients �69.6%�. The discrepancy in de��� patients �69.6%�. The discrepancy in de� �69.6%�. The discrepancy in de�69.6%�. The discrepancy in de�.6%�. The discrepancy in de�6%�. The discrepancy in de��. The discrepancy in de�. The discrepancy in de�The discrepancy in de� discrepancy in de�discrepancy in de� in de�in de� de�de�
termination of chemotherapy efficacy with the �se
of combined examination or medicinal pathomorphism
is ca�sed by limited acc�racy of the developed method
�7�.�%�. Statistical analysis of the data for the cases
with switched chemotherapy line with the obtained
medicinal pathomorphism� has revealed a significant
dependence between these two variables �p < �.���.
So� the switch of chemotherapy line significantly af�� the switch of chemotherapy line significantly af�the switch of chemotherapy line significantly af� of chemotherapy line significantly af�of chemotherapy line significantly af� chemotherapy line significantly af�line significantly af� significantly af�significantly af� af�af�
fects medicinal pathomorphism.
Myelotoxicity of ifosfamide at the dose of �� g/mІ has
been st�died. ΙV grade le�copenia by toxicity scale
�T� N�I� was observed in ���% patients treated
with high�dose ifosfamide and in ��% patients treated
with combination of cisplatin with doxor�bicin. In other
�7% patients treated with combination of cisplatin +
doxor�bicin� there has been registered hematologic
toxicity of ΙΙΙ degree by decreased le�kocyte co�nts.
There has been performed a comparison between
maximal le�copenia and d�ration of agran�locytosis.
Maximal le�copenia rates significantly differed after
the co�rses of high�dose ifosfamide and cisplatin +
doxor�bicin combination. After high�dose ifosfamide
co�rse maximal le�copenia was more freq�ent
�р = �.�4��� b�t d�ration of agran�locytosis in these
patients didn’t differ significantly from that in children
treated with cisplatin + doxor�bicin combination
�р = �.��74�.
In the st�dy of platelet co�nts after chemotherapy
with high�dose ifosfamide or cisplatin + doxor�bicin
combination it has been shown that ΙV degree toxicity
�platelet co�nts < ��·��9/l� was observed in �6 from
�4 �67%� chemotherapy co�rses with cisplatin +
doxor�bicin combination and only in � from �4 ��%�
chemotherapy co�rses with high�dose ifosfamide.
Platelet co�nts were not decreased after �� from
�4 ��4%� chemotherapy co�rses with high�dose
ifosfamide and after 6 from �4 ���%� co�rses with
cisplatin + doxor�bicin.
There has been fo�nd no significant difference
in hemoglobin levels and erythrocyte co�nts after
chemotherapy co�rses with high�dose ifosfamide
or combination of cisplatin with doxor�bicin.
So� after high�dose ifosfamide co�rse le�copenia
intensity was higher compared to that after the co�rse
of cisplatin combined with doxor�bicin �р = �.�4����
along with this agran�locytosis d�ration was practi� with this agran�locytosis d�ration was practi�with this agran�locytosis d�ration was practi� this agran�locytosis d�ration was practi�this agran�locytosis d�ration was practi� agran�locytosis d�ration was practi�agran�locytosis d�ration was practi� d�ration was practi�d�ration was practi� was practi�was practi�
cally similar in both therape�tic gro�ps �р = �.��74��
while the rate of ΙV degree thrombocytopenia was sig� the rate of ΙV degree thrombocytopenia was sig�the rate of ΙV degree thrombocytopenia was sig� rate of ΙV degree thrombocytopenia was sig�rate of ΙV degree thrombocytopenia was sig� of ΙV degree thrombocytopenia was sig�of ΙV degree thrombocytopenia was sig� ΙV degree thrombocytopenia was sig�degree thrombocytopenia was sig� thrombocytopenia was sig�thrombocytopenia was sig� was sig�was sig� sig�sig�
nificantly higher �by �.� fold� in the case of cisplatin +
doxor�bicin combination than in the case of high�dose
ifosfamide. These data evidenced on the safety of �se
of ifosfamide at a dose of �� g/mІ and on possibility
of its �se in clinical practice.
Pse�docaps�lifero�s t�mors were st�died
by Doppler USD �sing an algorithm for determina� determina�determina�
tion of chemotherapy efficacy. It has been fo�nd that
before operation enclosed persistent pse�docaps�le
was present in �� patients of the main gro�p. In the
cases when pse�docaps�le was absent in some t�mor
region� then with the �se of USD there has been per�� then with the �se of USD there has been per�then with the �se of USD there has been per� with the �se of USD there has been per�with the �se of USD there has been per� the �se of USD there has been per�the �se of USD there has been per� �se of USD there has been per��se of USD there has been per� of USD there has been per�of USD there has been per� USD there has been per�USD there has been per� there has been per�there has been per� has been per�has been per� been per�been per� per�per�
formed skin mapping of problematic region with de� skin mapping of problematic region with de�skin mapping of problematic region with de� of problematic region with de�of problematic region with de�
termination of its depth from skin to t�mor. Sometimes
if pse�docaps�le is placed above t�mor necrosis zone
and is thin�walled� it co�ld be damaged with following
effl�x of t�mor tiss�e in the wo�nd. S�ch sit�ation
is dangero�s beca�se of possible t�mor rec�rrence.
We have performed statistical analysis of the
state of pse�docaps�le and the risk of development
of local t�mor rec�rrence. It has been estimated with
significance р = �.��� that closeness of formed t�mor
pse�docaps�le red�ces local t�mor rec�rrence after
performed radical operative treatment. Therefore� the
st�dy of t�mor pse�docaps�le with the �se of USVD
prior to the s�rgery is important for planning of the
operative treatment. We s�ppose that total absence
of t�mor pse�docaps�le sho�ld be considered as con� t�mor pse�docaps�le sho�ld be considered as con�sho�ld be considered as con� be considered as con�be considered as con� considered as con�considered as con� as con�as con� con�con�
traindication for performance of organ�conserving
operation� while its partial absence — as relative con�� while its partial absence — as relative con�while its partial absence — as relative con� partial absence — as relative con�partial absence — as relative con� absence — as relative con�absence — as relative con� — as relative con�as relative con�
traindication for performance of organ�conserving
operation which req�ires preparatory mapping of risk
zone and its radical removal.
Also� there has been analyzed the dependence
between initial t�mor vol�me and the rate of local
rec�rrence. We have performed a correlation analysis
between variables of t�mor vol�me� the rate of rec�r� variables of t�mor vol�me� the rate of rec�r�variables of t�mor vol�me� the rate of rec�r� t�mor vol�me� the rate of rec�r�vol�me� the rate of rec�r�� the rate of rec�r�the rate of rec�r�
rence or its absence. No significant correlation be�. No significant correlation be�No significant correlation be� significant correlation be�significant correlation be� correlation be�correlation be� be�be�
tween these indexes was revealed �r = �.���.
��� Experimental Oncology ��� �������� ���� ���ne�
If t�mor vol�mes were distrib�ted in gro�ps
< ��� ml or > ���; 4��; ��� ml� their correlation with
rec�rrence cases was also insignificant �r = �.��; �.�4;
�.�� respectively�.
So� these data allow concl�de that t�mor vol�me
has no infl�ence on the rate of local rec�rrence.
That’s why t�mor vol�me co�ld be considered as con�’s why t�mor vol�me co�ld be considered as con�s why t�mor vol�me co�ld be considered as con� why t�mor vol�me co�ld be considered as con�why t�mor vol�me co�ld be considered as con� t�mor vol�me co�ld be considered as con�t�mor vol�me co�ld be considered as con� vol�me co�ld be considered as con�vol�me co�ld be considered as con� co�ld be considered as con�co�ld be considered as con� be considered as con�be considered as con� considered as con�considered as con� as con�as con� con�con�
traindication for organ�preserving operation only in the
cases when it is impossible to cover endoprosthesis
or transplant with soft tiss�es.
Organ�conserving operations were performed
in �6.9% patients. Local rec�rrence was fo�nd
in ��.�% patients. An index of � year relapse�free s�r�patients. An index of � year relapse�free s�r� An index of � year relapse�free s�r�
vival was 6� ± ��% �р = �.���� overall s�rvival —76.� ±
9% �р = �.���.
In concl�sion� introd�ction of ifosfamide at the
dose of �� g/m² in the treatment scheme of pediatric
patients with local form of osteosarcoma along with
individ�alization of pre�operative chemotherapy�
pre�operative analysis of NA�T efficacy and the state
of t�mor pse�docaps�le d�ring planning stage of or� pse�docaps�le d�ring planning stage of or� d�ring planning stage of or�
gan�conserving operations significantly improved on�
cologic and f�nctional res�lts of the therapy of patients
with large t�mor vol�me �p to the indexes comparable
with standard risk gro�p.
REFERENCES
1. Bielack S, Delling G, Kotz R, et al. Cooperative osteo-
sarcoma study group trial COSS-96 of intensive, risk-stratified
chemotherapy for osteosarcoma. Intern Sarcoma Meeting
Stuttgart, 2005. 103.
2. Ferrari S, Smeland S, Mercuri M, et al. �eoad�uvant che-�eoad�uvant che-
motherapy with high-dose ifosfamide, high-dose methotrexate,
cisplatin, and doxorubicin for patients with localized osteosar-
coma of the extremity� a �oint study by the Italian and Scan-� a �oint study by the Italian and Scan- a �oint study by the Italian and Scan-
dinavian Sarcoma Groups. J Clin Oncol 2005; 23� 8845–52.
3. Bruland ØS, Høifødt H, Sæter G, et al. Hematogenous
micrometastases in osteosarcoma patients. Clin Cancer Res
2005; 11� 4666–73.
4. Surgery of soft tissue and bone sarcoma. Principles and
operative techniques. Shugabeiker PX, Malauer ММ, eds.
Moscow� Meditsina, 1996� 245–308 (in Russian).
5. Machak G�. Modern possibilities and perspectives
of combined therapy of osteogenic sarcoma. Thesis Diss
Dr Med Sci, Moskow, 2007 (in Russian).
6. Picci P, Sangiorgi L, Rougraff B, et al. Relationship
of chemotherapy-induced necrosis and surgical margins
to local recurrence in osteosarcoma. J Clin Oncol 1994;
12� 2699–05.
7. Samardziski M, Zafiroski G, Janevska V, et al. Osteo-Osteo-
sarcoma� diagnosis and treatment. J Pediatr Sci 2010; 2� 2–15.
8. Rodriguez-Galindo C, Shah �, McCarville B, et al.
Outcome after local recurrence of osteosarcoma. Cancer 2004;
100� 1928–35.
9. Machak G�, Kochergina �V, Sen’ko OV, et al. Clin-
ico-radiological criteria of risk evaluation at the background
of preoperative chemotherapy of osteosarcoma. Union Of Rus-
sian Anticancer Organizations. http�netoncology.ru/press/
articles/710/712/ (in Russian).
10. Seeger LL, Widoff BE, Bassett LW, et al. Preop-
erative evaluation of osteosarcoma� value of gadopentetate
dimeglumine-enhanced MR imaging. Am J Roentgeno 1991;
157� 347–51.
11. Wafa H, Grimer R. Surgical options and outcomes
in bone sarcoma. Expert Rev Anticancer Therapy 2006;
6� 224–29.
12. Grimer R, Athanasou �, Gerrand C, et al. UK guide-
lines for the management of bone sarcomas. Sarcoma 2010;
2010. Article ID 317462, 1–14.
13. Dahlin DC, Unni KK. Bone tumors. General aspects
and data on 8542 cases. Cancer Res 2010; 75� 567–62.
14. Rosen G, Forscher C. Current combined treat-
ment of high-grade osteosarcomas. Oncology 1995;
9� http�//www.cancernetwork.com/display/article/10165/65653
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