Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2023; 22: 158-169
Диагностическая роль позитронно-эмиссионной томографии, совмещенной с компьютерной томографией, с 18F-фтордезоксиглюкозой и сцинтиграфии костей скелета у детей и молодых взрослых с костными саркомами: систематический обзор и метаанализ
https://doi.org/10.24287/1726-1708-2023-22-4-158-169Аннотация
Остеосаркома и саркома Юинга являются наиболее часто встречающимися первичными злокачественными заболеваниями костной ткани у детей. Точная диагностика и стадирование этих опухолей играют решающую роль в выборе оптимального лечения и прогнозировании исходов. В последние годы позитронно-эмиссионная томография, совмещенная с компьютерной томографией (ПЭТ/КТ), с 18F-фтордезоксиглюкозой (18F-ФДГ) все чаще используется в диагностике костных сарком для определения распространенности процесса совместно со сцинтиграфией костей скелета (СК) или вместо нее, но вопросы о диагностической значимости этих методов и выборе лучшего метода для ведения детей с костными саркомами остаются открытыми. Мы провели систематический обзор и метаанализ, чтобы сравнить диагностическую роль ПЭТ/КТ с 18F-ФДГ и СК у детей и молодых взрослых с костными саркомами при стадировании и рестадировании. Данное исследование было выполнено в соответствии с рекомендациями Кокрановского сообщества PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Двумя независимыми исследователями проведен поиск проспективных и ретроспективных исследований, оценивающих чувствительность и специфичность ПЭТ/КТ с 18F-ФДГ и СК в стадировании и рестадировании детей и молодых взрослых с костными саркомами, опубликованных за последние 15 лет. Качество включенных исследований было оценено с использованием инструмента QUADAS2. С применением программных пакетов STATA 17 и инструмента RevMan 5.3 рассчитывались сводные ROC-кривые для оценки общей диагностической ценности ПЭТ/КТ и СК. Оценка убедительности доказательств проводилась по системе GRADE. В данный систематический обзор и метаанализ были включены 8 исследований (530 пациентов с костными саркомами). Включенные исследования представляли 11 когорт пациентов (остеосаркома – 5 когорт, 305 пациентов; саркома Юинга – 6 когорт, 225 пациентов). Наши результаты показали, что ПЭТ/КТ с 18F-ФДГ обладает высокой чувствительностью в стадировании и рестадировании костных сарком – 94% (95% доверительный интервал (ДИ) 89–97). С другой стороны, СК показала меньшую чувствительность – 69% (95% ДИ 58–79), разница средних – 25% (95% ДИ 18,89–31,00), p < 0,001. Кроме того, наши результаты показали, что специфичность ПЭТ/КТ с 18F-ФДГ и СК была сопоставима – 96% (95% ДИ 83–99) и 92% (95% ДИ 82–97) соответственно, p = 0,15. Все результаты были подтверждены в анализе подгрупп пациентов с остеосаркомой и саркомой Юинга. На основании результатов нашего систематического обзора и метаанализа можно сделать вывод, что ПЭТ/КТ с 18F-ФДГ является более чувствительным методом для стадирования и рестадирования костных сарком у детей и молодых взрослых по сравнению с СК. Однако оба метода обладают высокой специфичностью. Учитывая полученные результаты метаанализа, будущие клинические исследования у детей с костными саркомами должны быть направлены на дальнейший набор данных по определению диагностической роли ПЭТ/КТ с 18F-ФДГ и СК как для детей с остеосаркомой, так и детей с саркомой Юинга для определения четких показаний и выбора наилучшего метода визуализации метастатического поражения костей скелета в целях разработки оптимального диагностического протокола.
Список литературы
1. Siegel R.L., Miller K.D., Wagle N.S., Jemal A. Cancer statistics, 2023. CA Cancer J Clin 2023; 73 (1): 17–48.
2. Шалыга И.Ф., Ачинович С.Л., Козловская Т.В., Мартемьянова Л.А., Турченко С.Ю., Авижец Ю.Н. Саркома Юинга. Проблемы здоровья и экологии 2018; 1 (55): 101–5.
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4. Anninga J.K., Gelderblom H., Fiocco M., Kroep J.R., Taminiau A.H.M., Hogendoorn P.C.W., Egeler M.R. Chemotherapeutic adjuvant treatment for osteosarcoma: Where do we stand? Eur J Cancer 2011; 47 (16): 2431–45.
5. Kaste S.C., Pratt C.B., Cain A.M., Jones-Wallace D.J., Rao B.N. Metastases detected at the time of diagnosis of primary pediatric extremity osteosarcoma at diagnosis: Imaging features. Cancer 1999; 86 (8): 160–8.
6. Esiashvili N., Goodman M., Marcus R.B. Changes in incidence and survival of ewing sarcoma patients over the past 3 decades: Surveillance epidemiology and end results data. J Pediatr Hematol Oncol 2008; 30 (6): 425–30.
7. Luetke A., Meyers P.A., Lewis I., Juergens H. Osteosarcoma treatment–where do we stand? A state of the art review. Cancer Treat Rev 2014; 40 (4): 523–32.
8. Ferrari S., Mercuri M., Bacci G., Bielack S.S., Jürgens H. Comment on “prognostic factors in high-grade osteosarcoma of the extremities or trunk: An analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols”. J Clin Oncol 2002; 20 (12): 2910–1.
9. Meyers P.A., Heller G., Healey J., Huvos A., Lane J., Marcove R., et al. Chemotherapy for nonmetastatic osteogenic sarcoma: The memorial sloan-kettering experience. J Clin Oncol 1992; 10 (1): 5–15.
10. Ferrari S., Bacci G., Picci P., Mercuri M., Briccoli A., Pinto D., et al. Long-term follow-up and post-relapse survival in patients with nonmetastatic osteosarcoma of the extremity treated with neoadjuvant chemotherapy. Ann Oncol 1997; 8 (8): 765–71.
11. Kempf-Bielack B., Bielack S.S., Jürgens H., Branscheid D., Berdel W.E., Exner G.U., et al. Osteosarcoma relapse after combined modality therapy: An analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS). J Clin Oncol 2005; 23 (3): 559–68.
12. Goorin A.M., Harris M.B., Bernstein M., Ferguson W., Devidas M., Siegal G.P.,et al. Phase II/III trial of etoposide and high-dose ifosfamide in newly diagnosed metastatic osteosarcoma: A pediatric oncology group trial. J Clin Oncol 2002; 20 (2): 426–33.
13. Grier H.E., Krailo M.D., Tarbell N.J., Link M.P., Fryer C.J.H., Pritchard D.J., et al. Addition of Ifosfamide and Etoposide to Standard Chemotherapy for Ewing’s Sarcoma and Primitive Neuroectodermal Tumor of Bone. N Engl J Med 2003; 348 (8): 694–701.
14. Womer R.B., West D.C., Krailo M.D., Dickman P.S., Pawel B.R., Grier H.E., et al. Randomized controlled trial of interval-compressed chemotherapy for the treatment of localized ewing sarcoma: A report from the children’s oncology group. J Clin Oncol 2012; 30 (33): 4148–54.
15. Moher D., Liberati A., Tetzlaff J., Altman D.G. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 2009; 62 (10): 1006–12.
16. Whiting P.F., Rutjes A.W.S., Westwood M.E., Mallett S., Deeks J.J., Reitsma J.B., et al. Quadas-2: A revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 2011; 155 (8): 529–36.
17. Egger M., Smith G.D., Schneider M., Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315 (7109): 629–34.
18. Brozek J.L., Akl E.A., Jaeschke R., Lang D.M., Bossuyt P., Glasziou P., et al. Grading quality of evidence and strength of recommendations in clinical practice guidelines: Part 2 of 3. the GRADE approach to grading quality of evidence about diagnostic tests and strategies. Allergy Eur J Allergy Clin Immunol 2009; 64 (8): 1109–16.
19. Foroutan F., Guyatt G., Zuk V., Vandvik P.O., Alba A.C., Mustafa R., et al. GRADE Guidelines 28: Use of GRADE for the assessment of evidence about prognostic factors: rating certainty in identification of groups of patients with different absolute risks. J Clin Epidemiol 2020; 121: 62–70.
20. Ulaner G.A., Magnan H., Healey J.H., Weber W.A., Meyers P.A. Is methylene diphosphonate bone scan necessary for initial staging of Ewing sarcoma if 18F-FDG PET/CT is performed? AJR Am J Roentgenol 2014; 202 (4): 859–67.
21. Tal A.L., Doshi H., Parkar F., Abraham T., Love C., Ye K., et al. The Utility of 18FDG PET/CT Versus Bone Scan for Identification of Bone Metastases in a Pediatric Sarcoma Population and a Review of the Literature. J Pediatr Hematol Oncol 2021; 43 (2): 52–8.
22. Ruggiero A., Lanni V., Librizzi A., Maurizi P., Attinà G., Mastrangelo S., et al. Diagnostic Accuracy of 18F-FDG PET/CT in the Staging and Assessment of Response to Chemotherapy in Children With Ewing Sarcoma. J Pediatr Hematol Oncol 2018; 40 (4): 277–84.
23. Quartuccio N., Fox J., Kuk D., Wexler L.H., Baldari S., Cistaro A., Schöder H., et al. Pediatric bone sarcoma: diagnostic performance of 18F-FDG PET/CT versus conventional imaging for initial staging and follow-up. AJR Am J Roentgenol 2015; 204 (1): 153–60.
24. Newman E.N., Jones R.L., Hawkins D.S. An evaluation of [F-18]-fluorodeoxy-D-glucose positron emission tomography, bone scan, and bone marrow aspiration/biopsy as staging investigations in Ewing sarcoma. Pediatr Blood Cancer 2013; 60 (7): 1113–7.
25. Hurley C., McCarville M.B., Shulkin B.L., Mao S., Wu J., Navid F. et al. Comparison of (18)F-FDGPET-CT and Bone Scintigraphy for Evaluation of Osseous Metastases in Newly Diagnosed and Recurrent Osteosarcoma. Pediatr Blood Cancer 2016; 63 (8): 1381–6.
26. Byun B.H., Kong C.B., Lim I., Kim B. I., Woon Choi C., Seok Song W., et al. Comparison of (18) F-FDG PET/CT and (99 m)Tc-MDP bone scintigraphy for detection of bone metastasis in osteosarcoma. Skeletal Radiol 2013; 42 (12): 1673–81.
27. Aryal A., Kumar V.S., Shamim S.A., Gamanagatti S., Khan S.A. What Is the Comparative Ability of 18F-FDG PET/CT, 99mTc-MDP Skeletal Scintigraphy, and Whole-body MRI as a Staging Investigation to Detect Skeletal Metastases in Patients with Osteosarcoma and Ewing Sarcoma? Clin Orthop Relat Res 2021; 479 (8): 1768–79.
28. Younis M.H., Abu-Hijleh H.A., Aldahamsheh O.O., Abualruz A., Thalib L. Meta-Analysis of the Diagnostic Accuracy of Primary Bone and Soft Tissue Sarcomas by 18F-FDGPET. Med Princ Pract 2020; 29 (5): 465–72.
29. Seth N., Seth I., Bulloch G., Hang Yue Siu A., Guo A., Chatterjee R., et al. 18F-FDG PET and PET/CT as a diagnostic method for Ewing sarcoma: A systematic review and meta-analysis. Pediatr Blood Cancer 2022; 69 (3): e29415.
30. Yang H.L., Liu T., Wang X.M., Xu Y., Deng S.M. Diagnosis of bone metastases: A meta-analysis comparing 18FDG PET, CT, MRI and bone scintigraphy. Eur Radiol 2011; 21 (12): 2604–17.
Pediatric Hematology/Oncology and Immunopathology. 2023; 22: 158-169
The diagnostic roles of fused 18F-fluorodeoxyglucose positron emission tomography/computed tomography and bone scintigraphy in children and young adults with bone sarcomas: a systematic review and meta-analysis
https://doi.org/10.24287/1726-1708-2023-22-4-158-169Abstract
Osteosarcoma and Ewing sarcoma are the most common primary malignant bone diseases in children. An accurate diagnosis and staging of these tumors play a pivotal role in choosing the optimal treatment and predicting outcomes. In recent years, fused 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) has been increasingly used in the diagnosis of bone sarcomas. It is frequently applied in conjunction with, or as a replacement for bone scintigraphy (BS), in order to determine the extent of the disease. However, the questions on the diagnostic significance of these methods and the choice of the most effective approach to the management of children with bone sarcomas still remain unanswered. We conducted a systematic review and meta-analysis to compare the diagnostic roles of 18F-FDG PET/CT and BS in staging and restaging of bone sarcomas in children and young adults. The study was carried out in accordance with the Cochrane PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Two independent researchers looked for prospective and retrospective studies evaluating the sensitivity and specificity of 18F-FDG PET/CT and BS in staging and restaging of bone sarcomas in children and young adults, published over the last 15 years. The quality of the included studies was assessed using the QUADAS-2 tool. Summary Receiver Operating Characteristic curves were calculated using STATA 17 software packages and the RevMan 5.3 tool to evaluate the overall diagnostic value of PET/CT and BS. The certainty of evidence was evaluated using the GRADE system. This systematic review and meta-analysis included 8 studies (530 patients with bone sarcomas). These studies used 11 patient cohorts (osteosarcoma: 5 cohorts, 305 patients; Ewing sarcoma: 6 cohorts, 225 patients). We discovered that 18F-FDG PET/CT had high sensitivity in staging and restaging of bone sarcomas (94% (95% confidence interval (CI) 89–97)). On the other hand, BS demonstrated lower sensitivity (69% (95% CI 58–79), the mean difference being 25% (95% CI 18.89–31.00), p < 0.001). At the same time, the specificity of 18F-FDG PET/CT and the specificity of BS were found to be comparable (96% (95% CI 83–99) and 92% (95% CI 82–97) respectively, p = 0.15). All the results were confirmed in a subgroup analysis of patients with osteosarcoma and Ewing sarcoma. The results of our systematic review and meta-analysis lead us to conclude that 18F-FDG PET/CT is a more sensitive method for staging and restaging of bone sarcomas in children and young adults, compared to BS. However, both methods have high specificity. Considering our findings, future clinical research in children with bone sarcomas should be aimed at further data collection to clarify the diagnostic roles of 18F-FDG PET/CT and BS both in children with osteosarcoma and in children with Ewing sarcoma, in order to identify clear indications and choose the best imaging method for detecting metastatic bone lesions, with the aim of developing an optimal diagnostic strategy.
References
1. Siegel R.L., Miller K.D., Wagle N.S., Jemal A. Cancer statistics, 2023. CA Cancer J Clin 2023; 73 (1): 17–48.
2. Shalyga I.F., Achinovich S.L., Kozlovskaya T.V., Martem'yanova L.A., Turchenko S.Yu., Avizhets Yu.N. Sarkoma Yuinga. Problemy zdorov'ya i ekologii 2018; 1 (55): 101–5.
3. [Electronic resource] Soft Tissue Cancer – Cancer Stat Facts. URL: https://seer.cancer.gov/statfacts/html/soft.html (accessed June 14, 2023).
4. Anninga J.K., Gelderblom H., Fiocco M., Kroep J.R., Taminiau A.H.M., Hogendoorn P.C.W., Egeler M.R. Chemotherapeutic adjuvant treatment for osteosarcoma: Where do we stand? Eur J Cancer 2011; 47 (16): 2431–45.
5. Kaste S.C., Pratt C.B., Cain A.M., Jones-Wallace D.J., Rao B.N. Metastases detected at the time of diagnosis of primary pediatric extremity osteosarcoma at diagnosis: Imaging features. Cancer 1999; 86 (8): 160–8.
6. Esiashvili N., Goodman M., Marcus R.B. Changes in incidence and survival of ewing sarcoma patients over the past 3 decades: Surveillance epidemiology and end results data. J Pediatr Hematol Oncol 2008; 30 (6): 425–30.
7. Luetke A., Meyers P.A., Lewis I., Juergens H. Osteosarcoma treatment–where do we stand? A state of the art review. Cancer Treat Rev 2014; 40 (4): 523–32.
8. Ferrari S., Mercuri M., Bacci G., Bielack S.S., Jürgens H. Comment on “prognostic factors in high-grade osteosarcoma of the extremities or trunk: An analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols”. J Clin Oncol 2002; 20 (12): 2910–1.
9. Meyers P.A., Heller G., Healey J., Huvos A., Lane J., Marcove R., et al. Chemotherapy for nonmetastatic osteogenic sarcoma: The memorial sloan-kettering experience. J Clin Oncol 1992; 10 (1): 5–15.
10. Ferrari S., Bacci G., Picci P., Mercuri M., Briccoli A., Pinto D., et al. Long-term follow-up and post-relapse survival in patients with nonmetastatic osteosarcoma of the extremity treated with neoadjuvant chemotherapy. Ann Oncol 1997; 8 (8): 765–71.
11. Kempf-Bielack B., Bielack S.S., Jürgens H., Branscheid D., Berdel W.E., Exner G.U., et al. Osteosarcoma relapse after combined modality therapy: An analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS). J Clin Oncol 2005; 23 (3): 559–68.
12. Goorin A.M., Harris M.B., Bernstein M., Ferguson W., Devidas M., Siegal G.P.,et al. Phase II/III trial of etoposide and high-dose ifosfamide in newly diagnosed metastatic osteosarcoma: A pediatric oncology group trial. J Clin Oncol 2002; 20 (2): 426–33.
13. Grier H.E., Krailo M.D., Tarbell N.J., Link M.P., Fryer C.J.H., Pritchard D.J., et al. Addition of Ifosfamide and Etoposide to Standard Chemotherapy for Ewing’s Sarcoma and Primitive Neuroectodermal Tumor of Bone. N Engl J Med 2003; 348 (8): 694–701.
14. Womer R.B., West D.C., Krailo M.D., Dickman P.S., Pawel B.R., Grier H.E., et al. Randomized controlled trial of interval-compressed chemotherapy for the treatment of localized ewing sarcoma: A report from the children’s oncology group. J Clin Oncol 2012; 30 (33): 4148–54.
15. Moher D., Liberati A., Tetzlaff J., Altman D.G. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 2009; 62 (10): 1006–12.
16. Whiting P.F., Rutjes A.W.S., Westwood M.E., Mallett S., Deeks J.J., Reitsma J.B., et al. Quadas-2: A revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 2011; 155 (8): 529–36.
17. Egger M., Smith G.D., Schneider M., Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315 (7109): 629–34.
18. Brozek J.L., Akl E.A., Jaeschke R., Lang D.M., Bossuyt P., Glasziou P., et al. Grading quality of evidence and strength of recommendations in clinical practice guidelines: Part 2 of 3. the GRADE approach to grading quality of evidence about diagnostic tests and strategies. Allergy Eur J Allergy Clin Immunol 2009; 64 (8): 1109–16.
19. Foroutan F., Guyatt G., Zuk V., Vandvik P.O., Alba A.C., Mustafa R., et al. GRADE Guidelines 28: Use of GRADE for the assessment of evidence about prognostic factors: rating certainty in identification of groups of patients with different absolute risks. J Clin Epidemiol 2020; 121: 62–70.
20. Ulaner G.A., Magnan H., Healey J.H., Weber W.A., Meyers P.A. Is methylene diphosphonate bone scan necessary for initial staging of Ewing sarcoma if 18F-FDG PET/CT is performed? AJR Am J Roentgenol 2014; 202 (4): 859–67.
21. Tal A.L., Doshi H., Parkar F., Abraham T., Love C., Ye K., et al. The Utility of 18FDG PET/CT Versus Bone Scan for Identification of Bone Metastases in a Pediatric Sarcoma Population and a Review of the Literature. J Pediatr Hematol Oncol 2021; 43 (2): 52–8.
22. Ruggiero A., Lanni V., Librizzi A., Maurizi P., Attinà G., Mastrangelo S., et al. Diagnostic Accuracy of 18F-FDG PET/CT in the Staging and Assessment of Response to Chemotherapy in Children With Ewing Sarcoma. J Pediatr Hematol Oncol 2018; 40 (4): 277–84.
23. Quartuccio N., Fox J., Kuk D., Wexler L.H., Baldari S., Cistaro A., Schöder H., et al. Pediatric bone sarcoma: diagnostic performance of 18F-FDG PET/CT versus conventional imaging for initial staging and follow-up. AJR Am J Roentgenol 2015; 204 (1): 153–60.
24. Newman E.N., Jones R.L., Hawkins D.S. An evaluation of [F-18]-fluorodeoxy-D-glucose positron emission tomography, bone scan, and bone marrow aspiration/biopsy as staging investigations in Ewing sarcoma. Pediatr Blood Cancer 2013; 60 (7): 1113–7.
25. Hurley C., McCarville M.B., Shulkin B.L., Mao S., Wu J., Navid F. et al. Comparison of (18)F-FDGPET-CT and Bone Scintigraphy for Evaluation of Osseous Metastases in Newly Diagnosed and Recurrent Osteosarcoma. Pediatr Blood Cancer 2016; 63 (8): 1381–6.
26. Byun B.H., Kong C.B., Lim I., Kim B. I., Woon Choi C., Seok Song W., et al. Comparison of (18) F-FDG PET/CT and (99 m)Tc-MDP bone scintigraphy for detection of bone metastasis in osteosarcoma. Skeletal Radiol 2013; 42 (12): 1673–81.
27. Aryal A., Kumar V.S., Shamim S.A., Gamanagatti S., Khan S.A. What Is the Comparative Ability of 18F-FDG PET/CT, 99mTc-MDP Skeletal Scintigraphy, and Whole-body MRI as a Staging Investigation to Detect Skeletal Metastases in Patients with Osteosarcoma and Ewing Sarcoma? Clin Orthop Relat Res 2021; 479 (8): 1768–79.
28. Younis M.H., Abu-Hijleh H.A., Aldahamsheh O.O., Abualruz A., Thalib L. Meta-Analysis of the Diagnostic Accuracy of Primary Bone and Soft Tissue Sarcomas by 18F-FDGPET. Med Princ Pract 2020; 29 (5): 465–72.
29. Seth N., Seth I., Bulloch G., Hang Yue Siu A., Guo A., Chatterjee R., et al. 18F-FDG PET and PET/CT as a diagnostic method for Ewing sarcoma: A systematic review and meta-analysis. Pediatr Blood Cancer 2022; 69 (3): e29415.
30. Yang H.L., Liu T., Wang X.M., Xu Y., Deng S.M. Diagnosis of bone metastases: A meta-analysis comparing 18FDG PET, CT, MRI and bone scintigraphy. Eur Radiol 2011; 21 (12): 2604–17.
