Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2024; 23: 45-55
Визуальная и количественная оценка промежуточной ПЭТ/КТ с 18F-фтордезоксиглюкозой у детей с лимфомой Ходжкина
https://doi.org/10.24287/1726-1708-2024-23-1-45-55Аннотация
Использование риск-адаптивной терапии у пациентов с лимфомой Ходжкина (ЛХ) позволяет выполнить деэскалацию протокола лечения и тем самым снизить частоту отдаленных побочных эффектов. Наличие метаболической ремиссии по результатам промежуточной (после 2 блоков химиотерапии) позитронно-эмиссионной томографии, совмещенной с компьютерной томографией (ПЭТ/КТ), является прогностическим фактором, влияющим на дальнейшую тактику лечения.
Общепринятая визуальная оценка по 5-балльной шкале (Deauville score, DS) промежуточной ПЭТ/КТ может быть подвержена неточностям. Одним из предложенных способов решения этой проблемы может быть использование количественного метода оценки (qPET).
Целью нашего исследования стало сравнение частоты несоответствия значений DS при использовании визуальной (vDS) и количественной (qDS) оценки выявленных очагов на изображениях промежуточной ПЭТ/КТ у детей с ЛХ.
Настоящее исследование одобрено независимым этическим комитетом и утверждено решением ученого совета НМИЦ ДГОИ им. Дмитрия Рогачева. Ретроспективно с использованием qPET были проанализированы результаты промежуточных ПЭТ/КТ у 115 пациентов с ЛХ (медиана возраста – 14 лет) и определена qDS. У всех пациентов были доступны инициальная ПЭТ/КТ для сравнения и данные истории болезни. Все исследования были выполнены в НМИЦ ДГОИ им. Дмитрия Рогачева в период с июня 2016 г. по март 2023 г. Результаты нашей работы показали, что при вышеуказанном подходе (наличие инициальной ПЭТ/КТ и доступа к истории болезни) расхождение в баллах между vDS и qDS составляло около 30 %. Отсутствие различий было отмечено только при установлении DS4 и DS5. В других случаях использование vDS привело к изменению балла у 31 (27,0 %) пациента (в 25 случаях было выставлено 2 балла по qDS против 3 баллов по vDS; в 6 – 3 балла по qDS против 4 баллов по vDS). Факторами, независимо связанными с бессобытийной выживаемостью, являлись значение vDS (отношение рисков 2,49 (1,26–4,93); p = 0,009), а также наличие объемной опухолевой массы (отношение рисков 3,12 (1,10–9,64); p = 0,048). Проведенный нами сравнительный анализ выявил различия в результатах, полученных при использовании vDS и qDS, но ни в одном случае при таком подходе не было отмечено занижения балла при оценке по vDS и, как следствие, не было деэскалации терапии. При хорошем сокращении объема опухоли по данным КТ, но сомнительных результатах оценки промежуточной ПЭТ/КТ по vDS (особенно при DS4 или DS3) следует использовать программное обеспечение для оценки по qDS.
Список литературы
1. Friedman D.L., Chen L., Wolden S., Buxton A., McCarten K., FitzGerald T.J., et al. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk hodgkin lymphoma: a report from the Children’s Oncology Group Study AHOD0031. J Clin Oncol 2014; 32 (32): 3651–8. DOI: 10.1200/JCO.2013.52.5410
2. Mauz-Körholz C., Metzger M.L., Kelly K.M., Schwartz C.L., Castellanos M.E., Dieckmann K., et al. Pediatric Hodgkin Lymphoma. J Clin Oncol 2015; 33 (27): 2975–85. DOI: 10.1200/JCO.2014.59.4853
3. Castellino S.M., Geiger A.M., Mertens A.C., Leisenring W.M., Tooze J.A., Goodman P., et al. Morbidity and mortality in long-term survivors of Hodgkin lymphoma: a report from the Childhood Cancer Survivor Study. Blood 2011; 117 (6): 1806–16. DOI: 10.1182/blood-2010-04-278796
4. Bhakta N., Liu Q., Yeo F., Baassiri M., Ehrhardt M.J., Srivastava D.K., et al. Cumulative burden of cardiovascular morbidity in paediatric, adolescent, and young adult survivors of Hodgkin’s lymphoma: an analysis from the St Jude Lifetime Cohort Study. Lancet Oncol 2016; 17 (9): 1325–34. DOI: 10.1016/S1470-2045(16)30215-7
5. Metzger M.L., Weinstein H.J., Hudson M.M., Billett A.L., Larsen E.C., Friedmann A., et al. Association between radiotherapy vs no radiotherapy based on early response to VAMP chemotherapy and survival among children with favorable-risk Hodgkin lymphoma. JAMA 2012; 307 (24): 2609–16. DOI: 10.1001/jama.2012.5847
6. Morton L.M., Onel K., Curtis R.E., Hungate E.A., Armstrong G.T. The Rising Incidence of Second Cancers: Patterns of Occurrence and Identification of Risk Factors for Children and Adults. Am Soc Clin Oncol Educ Book 2014: e57–67. DOI: 10.14694/EdBook_AM.2014.34.e57
7. Schaapveld M., Aleman B.M.P., van Eggermond A.M., Janus C.P.M., Krol A.D.G., van der Maazen R.W.M., et al. Second Cancer Risk Up to 40 Years after Treatment for Hodgkin’s Lymphoma. N Engl J Med 2015; 373 (26): 2499–511. DOI: 10.1056/NEJMoa1505949
8. Cheson B.D., Fisher R.I., Barrington S.F., Cavalli F., Schwartz L.H., Zucca E., et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 2014; 32 (27): 3059–67. DOI: 10.1200/JCO.2013.54.8800
9. Kostakoglu L., Cheson B.D. Current role of FDG PET/CT in lymphoma. Eur J Nucl Med Mol Imaging 2014; 41 (5): 1004–27. DOI: 10.1007/s00259-013-2686-2
10. Radford J., Illidge T., Counsell N., Hancock B., Pettengell R., Johnson P., et al. Results of a trial of PET-directed therapy for early-stage Hodgkin’s lymphoma. N Engl J Med 2015; 372 (17): 1598–607. DOI: 10.1056/NEJMoa1408648
11. Coyle M., Kostakoglu L., Evens A.M. The evolving role of response-adapted PET imaging in Hodgkin lymphoma. Ther Adv Hematol 2016; 7 (2): 108–25. DOI: 10.1177/2040620715625615
12. Bakhshi S., Bhethanabhotla S., Kumar R., Agarwal K., Sharma P., Thulkar S., et al. Posttreatment PET/CT Rather Than Interim PET/CT Using Deauville Criteria Predicts Outcome in Pediatric Hodgkin Lymphoma: A Prospective Study Comparing PET/CT with Conventional Imaging. J Nucl Med 2017; 58 (4): 577–83. DOI: 10.2967/jnumed.116.176511
13. Kelly K.M. Hodgkin lymphoma in children and adolescents: improving the therapeutic index. Blood 2015; 126 (22): 2452–8. DOI: 10.1182/blood-2015-07-641035
14. Kelly K.M., Cole P.D., Pei Q., Bush R., Roberts K.B., Hodgson D.C., et al. Response-adapted therapy for the treatment of children with newly diagnosed high risk Hodgkin lymphoma (AHOD0831): a report from the Children’s Oncology Group. Br J Haematol 2019; 187 (1): 39–48. DOI: 10.1111/bjh.16014
15. Meignan M., Gallamini A., Haioun C. Report on the First International Workshop on Interim-PET-Scan in Lymphoma. Leuk Lymphoma 2009; 50 (8): 1257–60. DOI: 10.1080/10428190903040048
16. Kluge R., Chavdarova L., Hoffmann M., Kobe C., Malkowski B., Montravers F., et al. Inter-Reader Reliability of Early FDG-PET/CT Response Assessment Using the Deauville Scale after 2 Cycles of Intensive Chemotherapy (OEPA) in Hodgkin’s Lymphoma. PLoS One 2016; 11 (3): e0149072. DOI: 10.1371/journal.pone.0149072
17. Hasenclever D., Kurch L., Mauz-Körholz C., Elsner A., Georgi T., Wallace H., et al. qPET – a quantitative extension of the Deauville scale to assess response in interim FDG-PET scans in lymphoma. Eur J Nucl Med Mol Imaging 2014; 41 (7): 1301–8. DOI: 10.1007/s00259-014-2715-9
18. Mauz-Körholz C., Landman-Parker J., Balwierz W., Ammann R.A., Anderson R.A., Attarbaschi A., et al. Response-adapted omission of radiotherapy and comparison of consolidation chemotherapy in children and adolescents with intermediate-stage and advanced-stage classical Hodgkin lymphoma (EuroNet-PHL-C1): a titration study with an open-label, embedded, mult. Lancet Oncol 2022; 23 (1): 125–37. DOI: 10.1016/S1470-2045(21)00470-8
19. Barrington S.F., Mikhaeel N.G., Kostakoglu L., Meignan M., Hutchings M., Müeller S.P., et al. Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on Malignant Lymphomas Imaging Working Group. J Clin Oncol 2014; 32 (27): 3048–58. DOI: 10.1200/JCO.2013.53.5229
20. Engert A., Haverkamp H., Kobe C., Markova J., Renner C., Ho A., et al. Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin’s lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial. Lancet 2012; 379 (9828): 1791–9. DOI: 10.1016/S0140-6736(11)61940-5
21. Gallamini A., Patti C., Viviani S., Rossi A., Fiore F., Di Raimondo F., et al. Early chemotherapy intensification with BEACOPP in advanced-stage Hodgkin lymphoma patients with a interim-PET positive after two ABVD courses. Br J Haematol 2011; 152 (5): 551–60. DOI: 10.1111/j.1365-2141.2010.08485.x
22. Cheson B.D., Kostakoglu L. FDG-PET for Early Response Assessment in Lymphomas: Part 1-Hodgkin Lymphoma. Oncology (Williston Park) 2017; 31 (1): 45–9.
23. Koga Y., Baba S., Fukano R., Nakamura K., Soejima T., Maeda N., et al. The Effect of Interim FDG-PET-guided Response-Adapted Therapy in Pediatric Patients with Hodgkin’s Lymphoma (HL-14): Protocol for a Phase II Study. Acta Med Okayama 2018; 72 (4): 437–40. DOI: 10.18926/AMO/56185
24. Ansell S.M. Hodgkin lymphoma: A 2020 update on diagnosis, risk-stratification, and management. Am J Hematol 2020; 95 (8): 978–89. DOI: 10.1002/ajh.25856
25. Han E.J., O J.H., Yoon H., Jung S.E., Park G., Choi B.O., et al. FDG PET/CT response in diffuse large B-cell lymphoma: Reader variability and association with clinical outcome. Medicine (Baltimore) 2016; 95 (39): e4983. DOI: 10.1097/MD.0000000000004983
26. Georgi T.W., Kurch L., Hasenclever D., Warbey V.S., Pike L., Radford J., et al. Interobserver variability in interim PET assessment in Hodgkin lymphoma-reasons and solutions. PLoS One 2023; 18 (3): e0283694. DOI: 10.1371/journal.pone.0283694
27. Georgi T.W., Zieschank A., Kornrumpf K., Kurch L., Sabri O., Korholz D., et al. Automatic classification of lymphoma lesions in FDG-PET-Differentiation between tumor and non-tumor uptake. PLoS One 2022; 17 (4): e0267275. DOI: 10.1371/journal.pone.0267275
Pediatric Hematology/Oncology and Immunopathology. 2024; 23: 45-55
Visual and quantitative assessment of interim 18F-fluorodeoxyglucose-positron emission tomography/computed tomography in children with Hodgkin lymphoma
https://doi.org/10.24287/1726-1708-2024-23-1-45-55Abstract
The use of risk-adaptive therapy in patients with Hodgkin lymphoma (HL) makes it possible to de-escalate treatment protocols, thereby decreasing the incidence of long-term adverse effects. Metabolic remission as detected by interim positron emission tomography/computed tomography (PET/CT) performed after 2 cycles of chemotherapy is a prognostic factor that could guide further treatment. The generally accepted Deauville 5-point scale (DS) used for the visual assessment of interim PET/CT scans may be prone to inaccuracies. One of the suggested ways to address this problem is to use a quantitative evaluation method (qPET).
The aim of our study was to determine the level of discrepancy between DS assigned after visual (vDS) and quantitative (qDS) assessment of detected lesions on interim PET/CT images in children with HL.
The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Interim PET/CT scans of 115 patients with HL (the median age was 14 years) were retrospectively analyzed using the quantitative (qPET) method to determine qDS. Baseline PET/CT scan findings and medical history data were available for all patients. All imaging studies were performed at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology between June 2016 and March 2023. Our results showed that with the above approach (availability of initial PET/CT scans and access to the patient’s medical history), discordance between vDS and qDS was about 30%. There was no difference in the patients with a DS of 4 and 5. In other cases, in 31 (27%) patients, vDS and qDS differed by one score: 25 patients with a qDS of 2 had a vDS of 3; 6 patients with a qDS of 3 had a vDS of 4. Factors independently associated with event-free survival were vDS (hazard ratio (HR) 2.49 (1.26–4.93), p = 0.009) and the presence of a bulky tumor (HR 3.12 (1.10–9.64), p = 0.048). Our comparative analysis revealed a discrepancy between the findings obtained by the visual and quantitative assessment methods. In our study, there were no cases of vDS underestimation and, as a consequence, no patients underwent treatment de-escalation. In HL patients with good tumor volume reduction on CT but ambiguous results of interim PET/CT evaluation performed using the vDS (especially in case of DS4 or DS3), quantification software should be used.
References
1. Friedman D.L., Chen L., Wolden S., Buxton A., McCarten K., FitzGerald T.J., et al. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk hodgkin lymphoma: a report from the Children’s Oncology Group Study AHOD0031. J Clin Oncol 2014; 32 (32): 3651–8. DOI: 10.1200/JCO.2013.52.5410
2. Mauz-Körholz C., Metzger M.L., Kelly K.M., Schwartz C.L., Castellanos M.E., Dieckmann K., et al. Pediatric Hodgkin Lymphoma. J Clin Oncol 2015; 33 (27): 2975–85. DOI: 10.1200/JCO.2014.59.4853
3. Castellino S.M., Geiger A.M., Mertens A.C., Leisenring W.M., Tooze J.A., Goodman P., et al. Morbidity and mortality in long-term survivors of Hodgkin lymphoma: a report from the Childhood Cancer Survivor Study. Blood 2011; 117 (6): 1806–16. DOI: 10.1182/blood-2010-04-278796
4. Bhakta N., Liu Q., Yeo F., Baassiri M., Ehrhardt M.J., Srivastava D.K., et al. Cumulative burden of cardiovascular morbidity in paediatric, adolescent, and young adult survivors of Hodgkin’s lymphoma: an analysis from the St Jude Lifetime Cohort Study. Lancet Oncol 2016; 17 (9): 1325–34. DOI: 10.1016/S1470-2045(16)30215-7
5. Metzger M.L., Weinstein H.J., Hudson M.M., Billett A.L., Larsen E.C., Friedmann A., et al. Association between radiotherapy vs no radiotherapy based on early response to VAMP chemotherapy and survival among children with favorable-risk Hodgkin lymphoma. JAMA 2012; 307 (24): 2609–16. DOI: 10.1001/jama.2012.5847
6. Morton L.M., Onel K., Curtis R.E., Hungate E.A., Armstrong G.T. The Rising Incidence of Second Cancers: Patterns of Occurrence and Identification of Risk Factors for Children and Adults. Am Soc Clin Oncol Educ Book 2014: e57–67. DOI: 10.14694/EdBook_AM.2014.34.e57
7. Schaapveld M., Aleman B.M.P., van Eggermond A.M., Janus C.P.M., Krol A.D.G., van der Maazen R.W.M., et al. Second Cancer Risk Up to 40 Years after Treatment for Hodgkin’s Lymphoma. N Engl J Med 2015; 373 (26): 2499–511. DOI: 10.1056/NEJMoa1505949
8. Cheson B.D., Fisher R.I., Barrington S.F., Cavalli F., Schwartz L.H., Zucca E., et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 2014; 32 (27): 3059–67. DOI: 10.1200/JCO.2013.54.8800
9. Kostakoglu L., Cheson B.D. Current role of FDG PET/CT in lymphoma. Eur J Nucl Med Mol Imaging 2014; 41 (5): 1004–27. DOI: 10.1007/s00259-013-2686-2
10. Radford J., Illidge T., Counsell N., Hancock B., Pettengell R., Johnson P., et al. Results of a trial of PET-directed therapy for early-stage Hodgkin’s lymphoma. N Engl J Med 2015; 372 (17): 1598–607. DOI: 10.1056/NEJMoa1408648
11. Coyle M., Kostakoglu L., Evens A.M. The evolving role of response-adapted PET imaging in Hodgkin lymphoma. Ther Adv Hematol 2016; 7 (2): 108–25. DOI: 10.1177/2040620715625615
12. Bakhshi S., Bhethanabhotla S., Kumar R., Agarwal K., Sharma P., Thulkar S., et al. Posttreatment PET/CT Rather Than Interim PET/CT Using Deauville Criteria Predicts Outcome in Pediatric Hodgkin Lymphoma: A Prospective Study Comparing PET/CT with Conventional Imaging. J Nucl Med 2017; 58 (4): 577–83. DOI: 10.2967/jnumed.116.176511
13. Kelly K.M. Hodgkin lymphoma in children and adolescents: improving the therapeutic index. Blood 2015; 126 (22): 2452–8. DOI: 10.1182/blood-2015-07-641035
14. Kelly K.M., Cole P.D., Pei Q., Bush R., Roberts K.B., Hodgson D.C., et al. Response-adapted therapy for the treatment of children with newly diagnosed high risk Hodgkin lymphoma (AHOD0831): a report from the Children’s Oncology Group. Br J Haematol 2019; 187 (1): 39–48. DOI: 10.1111/bjh.16014
15. Meignan M., Gallamini A., Haioun C. Report on the First International Workshop on Interim-PET-Scan in Lymphoma. Leuk Lymphoma 2009; 50 (8): 1257–60. DOI: 10.1080/10428190903040048
16. Kluge R., Chavdarova L., Hoffmann M., Kobe C., Malkowski B., Montravers F., et al. Inter-Reader Reliability of Early FDG-PET/CT Response Assessment Using the Deauville Scale after 2 Cycles of Intensive Chemotherapy (OEPA) in Hodgkin’s Lymphoma. PLoS One 2016; 11 (3): e0149072. DOI: 10.1371/journal.pone.0149072
17. Hasenclever D., Kurch L., Mauz-Körholz C., Elsner A., Georgi T., Wallace H., et al. qPET – a quantitative extension of the Deauville scale to assess response in interim FDG-PET scans in lymphoma. Eur J Nucl Med Mol Imaging 2014; 41 (7): 1301–8. DOI: 10.1007/s00259-014-2715-9
18. Mauz-Körholz C., Landman-Parker J., Balwierz W., Ammann R.A., Anderson R.A., Attarbaschi A., et al. Response-adapted omission of radiotherapy and comparison of consolidation chemotherapy in children and adolescents with intermediate-stage and advanced-stage classical Hodgkin lymphoma (EuroNet-PHL-C1): a titration study with an open-label, embedded, mult. Lancet Oncol 2022; 23 (1): 125–37. DOI: 10.1016/S1470-2045(21)00470-8
19. Barrington S.F., Mikhaeel N.G., Kostakoglu L., Meignan M., Hutchings M., Müeller S.P., et al. Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on Malignant Lymphomas Imaging Working Group. J Clin Oncol 2014; 32 (27): 3048–58. DOI: 10.1200/JCO.2013.53.5229
20. Engert A., Haverkamp H., Kobe C., Markova J., Renner C., Ho A., et al. Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin’s lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial. Lancet 2012; 379 (9828): 1791–9. DOI: 10.1016/S0140-6736(11)61940-5
21. Gallamini A., Patti C., Viviani S., Rossi A., Fiore F., Di Raimondo F., et al. Early chemotherapy intensification with BEACOPP in advanced-stage Hodgkin lymphoma patients with a interim-PET positive after two ABVD courses. Br J Haematol 2011; 152 (5): 551–60. DOI: 10.1111/j.1365-2141.2010.08485.x
22. Cheson B.D., Kostakoglu L. FDG-PET for Early Response Assessment in Lymphomas: Part 1-Hodgkin Lymphoma. Oncology (Williston Park) 2017; 31 (1): 45–9.
23. Koga Y., Baba S., Fukano R., Nakamura K., Soejima T., Maeda N., et al. The Effect of Interim FDG-PET-guided Response-Adapted Therapy in Pediatric Patients with Hodgkin’s Lymphoma (HL-14): Protocol for a Phase II Study. Acta Med Okayama 2018; 72 (4): 437–40. DOI: 10.18926/AMO/56185
24. Ansell S.M. Hodgkin lymphoma: A 2020 update on diagnosis, risk-stratification, and management. Am J Hematol 2020; 95 (8): 978–89. DOI: 10.1002/ajh.25856
25. Han E.J., O J.H., Yoon H., Jung S.E., Park G., Choi B.O., et al. FDG PET/CT response in diffuse large B-cell lymphoma: Reader variability and association with clinical outcome. Medicine (Baltimore) 2016; 95 (39): e4983. DOI: 10.1097/MD.0000000000004983
26. Georgi T.W., Kurch L., Hasenclever D., Warbey V.S., Pike L., Radford J., et al. Interobserver variability in interim PET assessment in Hodgkin lymphoma-reasons and solutions. PLoS One 2023; 18 (3): e0283694. DOI: 10.1371/journal.pone.0283694
27. Georgi T.W., Zieschank A., Kornrumpf K., Kurch L., Sabri O., Korholz D., et al. Automatic classification of lymphoma lesions in FDG-PET-Differentiation between tumor and non-tumor uptake. PLoS One 2022; 17 (4): e0267275. DOI: 10.1371/journal.pone.0267275
