Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2021; 20: 78-88
Светлоклеточная саркома почки у детей: клинические характеристики и результаты терапии
https://doi.org/10.24287/1726-1708-2021-20-4-78-88Аннотация
Светлоклеточная саркома почки (СКСП) – редкое злокачественное новообразование у детей, на долю которого приходится 2–5% всех опухолей почек. Целью исследования явилось изучение результатов терапии пациентов с СКСП, получавших лечение в условиях НМИЦ ДГОИ им. Дмитрия Рогачева. Проведен ретроспективный анализ пациентов с гистологически подтвержденным диагнозом СКСП, получавших лечение за период c января 2012 г. по февраль 2020 г. (98 мес). Данное исследование одобрено независимым этическим комитетом и утверждено решением ученого совета НМИЦ ДГОИ им. Дмитрия Рогачева. Анализировались демографические характеристики, клинические симптомы, метод постановки диагноза, объем проведенной терапии, исходы. Пациенты получали лечение по протоколам группы SIOP-RTSG (SIOP 93-01, SIOP-2001, SIOPRTSG-2016). Оценка распространенности процесса проводилась по классификации SIOP. Общая и бессобытийная выживаемость оценивались по методу Каплана–Майера. Анализ выживаемости проведен на 01.03.2021. В исследование включены 10 пациентов с СКСП. Медиана возраста на момент постановки диагноза СКСП составила 30,1 месяца (разброс 13,5–70,8 месяца). Все пациенты были лицами мужского пола. Длительность от возникновения первых симптомов/выявления опухоли до постановки диагноза составила 0,8 мес (разброс 0,1–3,2 мес). Диагноз установлен на основании клинико-рентгенологических данных (n = 9) и гистологического исследования биоптата опухоли (n = 1). Отдаленные метастазы на момент постановки диагноза выявлены у 1 (10%) пациента (локализация метастазов – легкие). Медиана объема опухоли составила 439 см3 (разброс 256–996 см3 ). Предоперационная полихимиотерапия (ПХТ) проведена всем больным (режим AV (актиномицин Д, винкристин) у 7 (70%) пациентов). При оценке динамики размеров опухоли после предоперационной ПХТ отмечено ее сокращение у 3/10 пациентов (у 1/7 при режиме AV), увеличение у 5/10 и стабилизация у 2/10 больных. Хирургическое лечение в объеме нефрэктомии проведено у всех пациентов. В 1 (10%) случае документирован интраоперационный разрыв опухоли. У 1 (10%) больного проведена торакотомия слева для исключения легочных метастазов. Распределение пациентов по локальным стадиям: I стадия – 4/10 (40%), II стадия – 2/10 (20%), III стадия – 4/10 (40%) (включая 1 больного с отдаленными метастазами). Адъювантная химиотерапия проводилась всем пациентам в соответствии со схемой лечения группы высокого риска: 7 пациентов получили 4–5-компонентный режим терапии, 3 – режим AVD (актиномицин Д, винкристин, доксорубицин). Лучевая терапия проводилась 6/10 (60%) пациентам. Исходы: 9/10 (90%) – живы, 1/10 (10%) пациент погиб (смерть, не связанная с опухолью). Трехлетняя бессобытийная выживаемость и общая выживаемость составили 78,8% (95% доверительный интервал (ДИ) 52,5–100) и 90,0% (95% ДИ 71,4–100) соответственно. Проведение комплексной интенсивной программной терапии у пациентов с СКСП позволяет добиться удовлетворительных результатов.
Список литературы
1. Gooskens S.L., Furtwängler R., Vujanic G.M., Dome J.S., Graf N., van den Heuvel-Eibrink M.M. Clear cell sarcoma of the kidney: a review. Eur J Cancer 2012; 48 (14): 2219– 26. DOI: 10.1016/j.ejca.2012.04.009
2. Kidd J.M. Exclusion of certain renal neoplasms from the category of Wilms’ tumor. Am J Pathol 1970 ;59: 16a.
3. Marsden H.B., Lawler W. Bone-metastasizing renal tumour of childhood. Br J Cancer 1978; 38: 437–41.
4. Gooskens S.L., Graf N., Furtwängler R., Spreafico F., Bergeron C., Ramírez-Villar G.L., et al. Position paper: Rationale for the treatment of children with CCSK in the UMBRELLA SIOP-RTSG 2016 protocol. Nat Rev Urol 2018; 15 (5): 309– 19. DOI: 10.1038/nrurol.2018.14
5. Vujanić G.M., Sandstedt B., Harms D., Kelsey A., Leuschner I., de Kraker J., et al. Revised International Society of Paediatric Oncology (SIOP) working classification of renal tumors of childhood. Med Pediatr Oncol 2002; 38 (2): 79–82. DOI: 10.1002/mpo.1276
6. Vujanić G.M., Gessler M., Ooms A.H.A.G., Collini P., Coulomb-l’Hermine A., D’Hooghe E., et al. Publisher Correction: The UMBRELLA SIOP-RTSG 2016 Wilms tumour pathology and molecular biology protocol. Nat Rev Urol 2019; 16 (9): 563. DOI: 10.1038/s41585- 019-0191-5
7. Nakata K., Colombet M., Stiller C.A., Pritchard-Jones K., Steliarova-Foucher E.; IICC-3 Contributors. Incidence of childhood renal tumours: An international population-based study. Int J Cancer 2020; 147 (12): 3313–27. DOI: 10.1002/ijc.33147
8. Argani P., Perlman E.J., Breslow N.E., Browning N.G., Green D.M., D’Angio G.J., et al. Clear cell sarcoma of the kidney: a review of 351 cases from the National Wilms Tumor Study Group Pathology Center. Am J Surg Pathol 2000; 24 (1): 4–18. DOI: 10.1097/00000478-200001000-00002
9. Furtwangler R., Gooskens S.L., van Tinteren H., de Kraker J., Schleiermacher G., Bergeron C., et al. Clear cell sarcomas of the kidney registered on International Society of Pediatric Oncology (SIOP) 93-01 and SIOP 2001 protocols: a report of the SIOP Renal Tumour Study Group. Eur J Cancer 2013; 49 (16): 3497–506.
10. Argani P., Pawel B., Szabo S., Reyes-Múgica M., Timmons C., Antonescu C.R. Diffuse Strong BCOR Immunoreactivity Is a Sensitive and Specific Marker for Clear Cell Sarcoma of the Kidney (CCSK) in Pediatric Renal Neoplasia. Am J Surg Pathol 2018; 42 (8): 1128–31. DOI: 10.1097/PAS.0000000000001089
11. Roy A., Kumar V., Zorman B., Fang E., Haines K.M., Doddapaneni H., et al. Recurrent internal tandem duplications of BCOR in clear cell sarcoma of the kidney. Nat Commun 2015; 6: 8891. DOI: 10.1038/ncomms9891
12. Ueno-Yokohata H., Okita H., Nakasato K., Akimoto S., Hata J., Koshinaga T., et al. Consistent in-frame internal tandem duplications of BCOR characterize clear cell sarcoma of the kidney. Nat Genet 2015; 47 (8): 861–3. DOI: 10.1038/ng.3338
13. Astolfi A., Melchionda F., Perotti D., Fois M., Indio V., Urbini M., et al. Whole transcriptome sequencing identifies BCOR internal tandem duplication as a common feature of clear cell sarcoma of the kidney. Oncotarget 2015; 6 (38): 40934–9. DOI: 10.18632/oncotarget.5882
14. Kenny C., Bausenwein S., Lazaro A., Furtwängler R., Gooskens S.L., van den Heuvel Eibrink M., et al. Mutually exclusive BCOR internal tandem duplications and YWHAE-NUTM2 fusions in clear cell sarcoma of kidney: not the full story. J Pathol 2016; 238 (5): 617–20. DOI: 10.1002/path.4693
15. O’Meara E., Stack D., Lee C.H., Garvin A.J., Morris T., Argani P., et al. Characterization of the chromosomal translocation t(10;17) (q22;p13) in clear cell sarcoma of kidney. J Pathol 2012; 227 (1): 72–80. DOI: 10.1002/path.3985
16. Han H., Bertrand K.C., Patel K.R., Fisher K.E., Roy A., Muscal J.A., et al. BCOR-CCNB3 fusion-positive clear cell sarcoma of the kidney. Pediatr Blood Cancer 2020; 67 (4): e28151. DOI: 10.1002/pbc.28151
17. Antonescu C.R., Kao Y.C., Xu B., Fujisawa Y., Chung C., Fletcher C.D.M., et al. Undifferentiated round cell sarcoma with BCOR internal tandem duplications (ITD) or YWHAE fusions: a clinicopathologic and molecular study. Mod Pathol 2020; 33 (9): 1669–77. DOI: 10.1038/s41379-020-0557-5
18. Kenny C., Grehan D., Ulas M., Banga G.B., Coulomb A., Vokuhl C., et al. Immunophenotype-Genotype Correlations in Clear Cell Sarcoma of Kidney-An Evaluation of Diagnostic Ancillary Studies. Pediatr Dev Pathol 2020; 23 (5): 345–51. DOI: 10.1177/1093526620910658
19. Ueno-Yokohata H., Okita H., Nakasato K., Hishiki T., Shirai R., Tsujimoto S., et al. Preoperative diagnosis of clear cell sarcoma of the kidney by detection of BCOR internal tandem duplication in circulating tumor DNA. Genes Chromosomes Cancer 2018; 57 (10): 525–9. DOI: 10.1002/gcc.22648
20. Kalapurakal J.A., Perlman E.J., Seibel N.L., Ritchey M., Dome J.S., Grundy P.E. Outcomes of patients with revised stage I clear cell sarcoma of kidney treated in National Wilms Tumor Studies 1–5. Int J Radiat Oncol Biol Phys 2013; 85 (2): 428–31. DOI: 10.1016/j.ijrobp.2012.04.023
21. Friesenbichler W., Lüftinger R., Kropshofer G., Henkel M., Amann G., Furtwängler R., et al. Clear cell sarcoma of the kidney in Austrian children: Long-term survival after relapse. Pediatr Blood Cancer 2021; 68 (5): e28860. DOI: 10.1002/pbc.28860
Pediatric Hematology/Oncology and Immunopathology. 2021; 20: 78-88
Clear cell sarcoma of the kidney in children: clinical characteristics and treatment results
https://doi.org/10.24287/1726-1708-2021-20-4-78-88Abstract
Clear cell sarcoma of the kidney (CCSK) is a rare malignant renal tumor in children, which accounts for 2–5% of pediatric kidney malignancies. The aim of the study was to analyze the results of therapy of patients with CCSK treated in Dmitry Rogachev National Medical Research Center оf Pediatric Hematology, Oncology and Immunology. Retrospective analysis of patients with a histologically confirmed diagnosis of CCSK treated for the period 01.2012–02.2020 (98 months) was done. The study was approved by the Independent Ethics Committee and the Scientific Council of the D. Rogachev NMRCPHOI of the Ministry of Healthcare of the Russian Federation. Demographic characteristics, clinical symptoms, methods of diagnosis, and treatment modalities were analyzed. Patients were treated according to the protocols of the SIOP-RTSG group (SIOP 93-01, SIOP-2001, SIOP-RTSG-2016). The stage was assigned according to the SIOP classification. Overall and event-free survival was assessed by the Kaplan–Mayer method. The analysis of the results was carried out on 01.03.2021. The analysis included 10 patients with CCSK. The median age at the time of diagnosis of CCSK was 30.1 months (range 13.5–70.8 months). All patients were male. The duration from the onset of the first symptoms/detection of the tumor to the diagnosis was 0.8 months (range 0.1–3.2 months). The diagnosis was established on the basis of clinical and radiological data (n = 9) and biopsy (n = 1). Distant metastases at the time of diagnosis were detected in 1 (10%) patient (localization of metastases - lungs). The median tumor volume was 439 cm3 (range 256–996 cm3 ). Preoperative chemotherapy was performed in all patients (AV regimen (actinomycin D, doxorubicin) in 7 (70%) patients). Assessment of response after preoperative chemotherapy showed tumor regression in 3/10 (in 1/7 with AV regimen), tumor progression in 5 and stable disease in 2 patients. Surgical treatment in the extent of nephrectomy was performed in all patients. In 1 (10%) case, intraoperative tumor rupture was documented. Distribution of patients by local stages: I – 4/10 (40%), II – 2/10 (20%), III – 4/10 (40%) (including 1 patient with distant metastases). In 1 patient, a left thoracotomy was performed to exclude lung metastases. Adjuvant chemotherapy was performed in all patients in accordance with the relevant protocols of the high-risk group: 7 – 4–5-drug regimen, 3 – AVD regimen (actinomycin D, vincristine, doxorubicin). Radiation therapy was performed in 6/10 (60%) patients. Outcomes: 9/10 (90%) – alive, 1/10 (10%) patient died (non-tumor-related death). 3-year event-free survival and overall survival were 78.8% (95% confidence interval (CI) 52.5–100) and 90.0% (95% CI 71.4–100) respectively. Intensive program therapy in patients with CCSK allows to achieve satisfactory results of treatment.
References
1. Gooskens S.L., Furtwängler R., Vujanic G.M., Dome J.S., Graf N., van den Heuvel-Eibrink M.M. Clear cell sarcoma of the kidney: a review. Eur J Cancer 2012; 48 (14): 2219– 26. DOI: 10.1016/j.ejca.2012.04.009
2. Kidd J.M. Exclusion of certain renal neoplasms from the category of Wilms’ tumor. Am J Pathol 1970 ;59: 16a.
3. Marsden H.B., Lawler W. Bone-metastasizing renal tumour of childhood. Br J Cancer 1978; 38: 437–41.
4. Gooskens S.L., Graf N., Furtwängler R., Spreafico F., Bergeron C., Ramírez-Villar G.L., et al. Position paper: Rationale for the treatment of children with CCSK in the UMBRELLA SIOP-RTSG 2016 protocol. Nat Rev Urol 2018; 15 (5): 309– 19. DOI: 10.1038/nrurol.2018.14
5. Vujanić G.M., Sandstedt B., Harms D., Kelsey A., Leuschner I., de Kraker J., et al. Revised International Society of Paediatric Oncology (SIOP) working classification of renal tumors of childhood. Med Pediatr Oncol 2002; 38 (2): 79–82. DOI: 10.1002/mpo.1276
6. Vujanić G.M., Gessler M., Ooms A.H.A.G., Collini P., Coulomb-l’Hermine A., D’Hooghe E., et al. Publisher Correction: The UMBRELLA SIOP-RTSG 2016 Wilms tumour pathology and molecular biology protocol. Nat Rev Urol 2019; 16 (9): 563. DOI: 10.1038/s41585- 019-0191-5
7. Nakata K., Colombet M., Stiller C.A., Pritchard-Jones K., Steliarova-Foucher E.; IICC-3 Contributors. Incidence of childhood renal tumours: An international population-based study. Int J Cancer 2020; 147 (12): 3313–27. DOI: 10.1002/ijc.33147
8. Argani P., Perlman E.J., Breslow N.E., Browning N.G., Green D.M., D’Angio G.J., et al. Clear cell sarcoma of the kidney: a review of 351 cases from the National Wilms Tumor Study Group Pathology Center. Am J Surg Pathol 2000; 24 (1): 4–18. DOI: 10.1097/00000478-200001000-00002
9. Furtwangler R., Gooskens S.L., van Tinteren H., de Kraker J., Schleiermacher G., Bergeron C., et al. Clear cell sarcomas of the kidney registered on International Society of Pediatric Oncology (SIOP) 93-01 and SIOP 2001 protocols: a report of the SIOP Renal Tumour Study Group. Eur J Cancer 2013; 49 (16): 3497–506.
10. Argani P., Pawel B., Szabo S., Reyes-Múgica M., Timmons C., Antonescu C.R. Diffuse Strong BCOR Immunoreactivity Is a Sensitive and Specific Marker for Clear Cell Sarcoma of the Kidney (CCSK) in Pediatric Renal Neoplasia. Am J Surg Pathol 2018; 42 (8): 1128–31. DOI: 10.1097/PAS.0000000000001089
11. Roy A., Kumar V., Zorman B., Fang E., Haines K.M., Doddapaneni H., et al. Recurrent internal tandem duplications of BCOR in clear cell sarcoma of the kidney. Nat Commun 2015; 6: 8891. DOI: 10.1038/ncomms9891
12. Ueno-Yokohata H., Okita H., Nakasato K., Akimoto S., Hata J., Koshinaga T., et al. Consistent in-frame internal tandem duplications of BCOR characterize clear cell sarcoma of the kidney. Nat Genet 2015; 47 (8): 861–3. DOI: 10.1038/ng.3338
13. Astolfi A., Melchionda F., Perotti D., Fois M., Indio V., Urbini M., et al. Whole transcriptome sequencing identifies BCOR internal tandem duplication as a common feature of clear cell sarcoma of the kidney. Oncotarget 2015; 6 (38): 40934–9. DOI: 10.18632/oncotarget.5882
14. Kenny C., Bausenwein S., Lazaro A., Furtwängler R., Gooskens S.L., van den Heuvel Eibrink M., et al. Mutually exclusive BCOR internal tandem duplications and YWHAE-NUTM2 fusions in clear cell sarcoma of kidney: not the full story. J Pathol 2016; 238 (5): 617–20. DOI: 10.1002/path.4693
15. O’Meara E., Stack D., Lee C.H., Garvin A.J., Morris T., Argani P., et al. Characterization of the chromosomal translocation t(10;17) (q22;p13) in clear cell sarcoma of kidney. J Pathol 2012; 227 (1): 72–80. DOI: 10.1002/path.3985
16. Han H., Bertrand K.C., Patel K.R., Fisher K.E., Roy A., Muscal J.A., et al. BCOR-CCNB3 fusion-positive clear cell sarcoma of the kidney. Pediatr Blood Cancer 2020; 67 (4): e28151. DOI: 10.1002/pbc.28151
17. Antonescu C.R., Kao Y.C., Xu B., Fujisawa Y., Chung C., Fletcher C.D.M., et al. Undifferentiated round cell sarcoma with BCOR internal tandem duplications (ITD) or YWHAE fusions: a clinicopathologic and molecular study. Mod Pathol 2020; 33 (9): 1669–77. DOI: 10.1038/s41379-020-0557-5
18. Kenny C., Grehan D., Ulas M., Banga G.B., Coulomb A., Vokuhl C., et al. Immunophenotype-Genotype Correlations in Clear Cell Sarcoma of Kidney-An Evaluation of Diagnostic Ancillary Studies. Pediatr Dev Pathol 2020; 23 (5): 345–51. DOI: 10.1177/1093526620910658
19. Ueno-Yokohata H., Okita H., Nakasato K., Hishiki T., Shirai R., Tsujimoto S., et al. Preoperative diagnosis of clear cell sarcoma of the kidney by detection of BCOR internal tandem duplication in circulating tumor DNA. Genes Chromosomes Cancer 2018; 57 (10): 525–9. DOI: 10.1002/gcc.22648
20. Kalapurakal J.A., Perlman E.J., Seibel N.L., Ritchey M., Dome J.S., Grundy P.E. Outcomes of patients with revised stage I clear cell sarcoma of kidney treated in National Wilms Tumor Studies 1–5. Int J Radiat Oncol Biol Phys 2013; 85 (2): 428–31. DOI: 10.1016/j.ijrobp.2012.04.023
21. Friesenbichler W., Lüftinger R., Kropshofer G., Henkel M., Amann G., Furtwängler R., et al. Clear cell sarcoma of the kidney in Austrian children: Long-term survival after relapse. Pediatr Blood Cancer 2021; 68 (5): e28860. DOI: 10.1002/pbc.28860
