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CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2021; 42(05): 415-425
DOI: 10.1055/s-0041-1730240
Original Article

Role of Interim PET Scan after 2 Cycles of ABVD in Pediatric Hodgkin Lymphoma: Retrospective Multicenter Study from South India

Arun Seshachalam
1   Dr. GVN Cancer Institute, Tiruchirappalli, Tamil Nadu, India
,
Shashidhar V. Karpurmath‡   *
2   Vydehi Institute of Medical Sciences and Research Centre, Bengaluru, Karnataka, India
,
Krishnakumar Rathnam‡   *
3   Meenakshi Mission Hospital and Research Center, Madurai, Tamil Nadu, India
,
Arathi Srinivasan
4   Kanchi Kamakoti CHILDS Trust Hospital, Nungambakkam, Chennai, Tamil Nadu, India
,
Julius Scott
5   Sri Ramachandra Medical Center, Porur, Chennai, Tamil Nadu, India
,
Raman S. G.
6   Madras Cancer Care Foundation, Chennai, Tamil Nadu, India
,
M. Janarthinakani
6   Madras Cancer Care Foundation, Chennai, Tamil Nadu, India
,
Krishna Prasad
7   Mangalore Institute of Oncology, Mangaluru, Karnataka, India
,
Channappa Patil
8   Apollo Hospital, Bengaluru, Karnataka, India
,
Parameswaran Anoop
8   Apollo Hospital, Bengaluru, Karnataka, India
,
Neelesh Reddy
9   Columbia Asia Hospital, Bengaluru, Karnataka, India
,
Satish Kumar Anumula
9   Columbia Asia Hospital, Bengaluru, Karnataka, India
,
Sirigeri Prabhakar Roopa
9   Columbia Asia Hospital, Bengaluru, Karnataka, India
,
Krishna Reddy Golamari
10   Manipal Hospital, Vijayawada, Andhra Pradesh, India
,
Madhav Danthala
10   Manipal Hospital, Vijayawada, Andhra Pradesh, India
,
Basawantrao Malipatil
9   Columbia Asia Hospital, Bengaluru, Karnataka, India
,
Bharath Rangarajan
11   Kovai Medical Center and Hospital, Coimbatore, Tamil Nadu, India
,
Karthik S. Udupa
12   Kasturba Medical College, Manipal, Karnataka, India
,
Manjunath Nandennavar
2   Vydehi Institute of Medical Sciences and Research Centre, Bengaluru, Karnataka, India
,
Kesavan Niraimathi
13   Fenivi Research Solutions, Chennai, Tamil Nadu, India
› Author Affiliations Funding Local investigators had the responsibility of collecting the data and entering into the database. Preexisting local resources were used to collect the required information. Hence, no funding was required for this research project
› Further Information
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Abstract

Introduction Most Indian centers use Adriamycin/Bleomycin/Vinblastine/Dacarba-zine (ABVD) chemotherapy for pediatric Hodgkin lymphoma (pHL). To reduce the late toxicity, robust predictive markers are needed to risk stratify pHL patients, thereby limiting the number of chemotherapy cycles and omitting radiation for low-risk and intensifying treatment for high-risk children.

Objective This study was conducted to analyze the outcome of pHL patients treated with ABVD and various factors predicting the outcome.

Materials and Methods This retrospective study analyzed the outcome of 113 consecutive pHL children treated with ABVD chemotherapy from 11 tertiary care centers in South India from 2009 to 2019.

Results The median duration of follow-up was 2.73 years. The median age was 13 years. B symptoms are seen in 50.5% patients, bulky disease in 23%, and stage IV in 28.3%. Of 113 pHL, 69% had a positron emission tomography (PET) and 31% had computed tomography (CT)-based staging. Stage IV (37.1%) and extranodal involvement (31.2%) were seen more often with PET than with CT staging (8.5 and 2.8%, respectively). Among 64 patients with interim PET scan after two cycles (iPET2), 20.3% did not achieve complete remission (CR) and no factors were significantly associated. The 4-year event-free survival (EFS) rate of the entire cohort was 86%. The 4-year EFS rate was 93% for patients with CR in iPET2 and 52% for patients not achieving CR. The only independent predictor of low EFS was iPET2 response (p < 0.05).

Conclusion Our study confirms the prognostic role of PET scan staging and response assessment. Not achieving CR on the iPET2 scan indicates poor prognosis and warrants clinical trial enrollment for a better outcome.

Keywords

iPET2 - pediatric Hodgkin lymphoma - prognosis - relapse - CMOG

* Both authors contributed equally to the manuscript.


Supplementary Material



Publication History

Article published online:
06 July 2021

© 2021. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

  • 1 Horning SJ, Williams J, Bartlett NL. et al. Assessment of the Stanford V regimen and consolidative radiotherapy for bulky and advanced Hodgkin’s disease: Eastern Cooperative Oncology Group pilot study E1492. J Clin Oncol 2000; 18 (05) 972-980
    CrossrefPubMedGoogle Scholar
  • 2 Radford JA, Rohatiner AZS, Ryder WDJ. et al. ChlVPP/EVA hybrid versus the weekly VAPEC-B regimen for previously untreated Hodgkin’s disease. J Clin Oncol 2002; 20 (13) 2988-2994
    CrossrefPubMedGoogle Scholar
  • 3 Chisesi T, Federico M, Levis A. et al. Intergruppo Italiano Linfomi. ABVD versus Stanford V versus MEC in unfavourable Hodgkin’s lymphoma: results of a randomised trial. Ann Oncol 2002; 13 (Suppl. 01) 102-106
    CrossrefPubMedGoogle Scholar
  • 4 Diehl V, Franklin J, Pfreundschuh M. et al. German Hodgkin’s Lymphoma Study Group. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin’s disease. N Engl J Med 2003; 348 (24) 2386-2395
    CrossrefPubMedGoogle Scholar
  • 5 Weiner MA, Leventhal B, Brecher ML. et al. Randomized study of intensive MOPP-ABVD with or without low-dose total-nodal radiation therapy in the treatment of stages IIB, IIIA2, IIIB, and IV Hodgkin’s disease in pediatric patients: a Pediatric Oncology Group study. J Clin Oncol 1997; 15 (08) 2769-2779
    CrossrefPubMedGoogle Scholar
  • 6 Maity A, Goldwein JW, Lange B, D’Angio GJ. Comparison of high-dose and low-dose radiation with and without chemotherapy for children with Hodgkin’s disease: an analysis of the experience at the Children’s Hospital of Philadelphia and the Hospital of the University of Pennsylvania. J Clin Oncol 1992; 10 (06) 929-935
    CrossrefPubMedGoogle Scholar
  • 7 Koh E-S, Tran TH, Heydarian M. et al. A comparison of mantle versus involved-field radiotherapy for Hodgkin’s lymphoma: reduction in normal tissue dose and second cancer risk. Radiat Oncol 2007; 2 (01) 13 DOI: 10.1186/1748-717X-2-13.
    CrossrefPubMedGoogle Scholar
  • 8 Brämswig JH, Höornig-Franz I, Riepenhausen M, Schellong G. The challenge of pediatric Hodgkin’s disease-where is the balance between cure and long-term toxicity?: A report of the West German multicenter studies DAL-HD-78, DAL-HD-82 and DAL-HD-85. Leuk Lymphoma 1990; 3 (03) 183-193
    CrossrefPubMedGoogle Scholar
  • 9 Schellong G. Treatment of children and adolescents with Hodgkin’s disease: the experience of the German-Austrian Paediatric Study Group. Baillieres Clin Haematol 1996; 9 (03) 619-634
    CrossrefPubMedGoogle Scholar
  • 10 Schellong G, Hörnig-Franz I, Rath B. et al. [Reducing radiation dosage to 20-30 Gy in combined chemo-/radiotherapy of Hodgkin’s disease in childhood. A report of the cooperative DAL-HD-87 therapy study]. Klin Padiatr 1994; 206 (04) 253-262
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Schellong G, Pötter R, Brämswig J. et al. The German-Austrian Pediatric Hodgkin’s Disease Study Group. High cure rates and reduced long-term toxicity in pediatric Hodgkin’s disease: the German-Austrian multicenter trial DAL-HD-90. J Clin Oncol 1999; 17 (12) 3736-3744
    CrossrefPubMedGoogle Scholar
  • 12 Donaldson SS, Kaplan HS. Complications of treatment of Hodgkin’s disease in children. Cancer Treat Rep 1982; 66 (04) 977-989 http://www.ncbi.nlm.nih.gov/pubmed/7074658 Accessed April 15 2021
    Google Scholar
  • 13 Mauz-Körholz C, Hasenclever D, Dörffel W. et al. Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin’s lymphoma: the GPOH-HD-2002 study. J Clin Oncol 2010; 28 (23) 3680-3686
    CrossrefPubMedGoogle Scholar
  • 14 Ozuah NW, Marcus KJ, LaCasce AS, Billett AL. Excellent outcomes following response-based omission of radiotherapy in children and adolescents with intermediate or high-risk Hodgkin lymphoma. J Pediatr Hematol Oncol 2018; 40 (06) e338-e342
    CrossrefPubMedGoogle Scholar
  • 15 Kapoor G, Advani SH, Dinshaw KA. et al. Treatment results of Hodgkin’s disease in Indian children. Pediatr Hematol Oncol 1995; 12 (06) 559-569
    CrossrefPubMedGoogle Scholar
  • 16 Arya LS, Dinand V, Thavaraj V. et al. Hodgkin’s disease in Indian children: outcome with chemotherapy alone. Pediatr Blood Cancer 2006; 46 (01) 26-34
    CrossrefPubMedGoogle Scholar
  • 17 Büyükpamukçu M, Varan A, Akyüz C. et al. The treatment of childhood Hodgkin lymphoma: improved survival in a developing country. Acta Oncol 2009; 48 (01) 44-51
    CrossrefPubMedGoogle Scholar
  • 18 Fadoo Z, Belgaumi A, Alam M, Azam I, Naqvi A. Pediatric lymphoma: a 10-year experience at a tertiary care hospital in Pakistan. J Pediatr Hematol Oncol 2010; 32 (01) e14-e18
    CrossrefPubMedGoogle Scholar
  • 19 Trehan A, Singla S, Marwaha RK, Bansal D, Srinivasan R. Hodgkin lymphoma in children: experience in a tertiary care centre in India. J Pediatr Hematol Oncol 2013; 35 (03) 174-179
    CrossrefPubMedGoogle Scholar
  • 20 Diefenbach CS, Li H, Hong F. et al. Evaluation of the International Prognostic Score (IPS-7) and a Simpler Prognostic Score (IPS-3) for advanced Hodgkin lymphoma in the modern era. Br J Haematol 2015; 171 (04) 530-538
    CrossrefPubMedGoogle Scholar
  • 21 Ganesan P, Dhanushkodi M, Ganesan TS. et al. Prognostic utility of the IPS 3 score for predicting outcomes in advanced Hodgkin lymphoma. Clin Lymphoma Myeloma Leuk 2019; 19 (02) 116-122
    CrossrefPubMedGoogle Scholar
  • 22 Moccia AA, Donaldson J, Chhanabhai M. et al. International Prognostic Score in advanced-stage Hodgkin’s lymphoma: altered utility in the modern era. J Clin Oncol 2012; 30 (27) 3383-3388
    CrossrefPubMedGoogle Scholar
  • 23 Tartas NE, Zerga M, Santos MI, Alfonso G, Amoroso M. International Prognostic Score (IPS) is not useful in stages I–II Hodgkin’s lymphoma (HL) - an experience of the Buenos Aires Leukemia Group (BALG). Blood 2006; 108: 11 http://www.bloodjournal.org/content/108/11/4659?sso-checked=true Accessed April 15, 2021
    CrossrefPubMedGoogle Scholar
  • 24 Schwartz CL, Chen L, McCarten K. et al. Childhood Hodgkin International Prognostic Score (CHIPS) predicts event-free survival in Hodgkin lymphoma: a report from the Children’s Oncology Group. Pediatr Blood Cancer 2017; 64: 4 DOI: 10.1002/pbc.26278.
    CrossrefPubMedGoogle Scholar
  • 25 Khedr R, Mahfouz S, Fathy H, Shalaby L. Childhood Hodgkin International Prognostic Score (CHIPS) and interim PET can predict event-free survival in Hodgkin lymphoma. Clin Lymphoma Myeloma Leuk 2019; 19: S311 DOI: 10.1016/j.clml.2019.07.279.
    CrossrefGoogle Scholar
  • 26 Metzger ML, Weinstein HJ, Hudson MM. 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) 2609-2616 DOI: 10.1001/jama.2012.5847.
    CrossrefPubMedGoogle Scholar
  • 27 Bakhshi S, Bhethanabhotla S, Kumar R. 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 (04) 577-583
    CrossrefPubMedGoogle Scholar
  • 28 Furth C, Steffen IG, Amthauer H. et al. Early and late therapy response assessment with [18F]fluorodeoxyglucose positron emission tomography in pediatric Hodgkin’s lymphoma: analysis of a prospective multicenter trial. J Clin Oncol 2009; 27 (26) 4385-4391
    CrossrefPubMedGoogle Scholar
  • 29 Hussein S. 1, Moustafa H 1, Omar W 2, El-Haddad, A 3. FDG-PET/CT in Early Assessment of Response to Therapy in Pediatric Hodgkin Lymphoma. Egyptian J.Nucl. Med., Vol 7 2013
  • 30 Ilivitzki A, Radan L, Ben-Arush M. Israel O, Ben-Barak A. Early interim FDG PET/CT prediction of treatment response and prognosis in pediatric Hodgkin disease-added value of low-dose CT. Pediatr Radiol 2013; 43 (01) 86-92
    CrossrefPubMedGoogle Scholar
  • 31 Seshachalam A, Karpurmath SV, Rathnam K. et al. Does interim PET scan after 2 cycles of ABVD predict outcome in Hodgkin lymphoma? Real-world evidence. J Glob Oncol 2019; 5 (05) 1-13
    CrossrefPubMedGoogle Scholar
  • 32 Dann EJ, Bairey O, Bar-Shalom R. et al. Modification of initial therapy in early and advanced Hodgkin lymphoma, based on interim PET/CT is beneficial: a prospective multicentre trial of 355 patients. Br J Haematol 2017; 178 (05) 709-718
    CrossrefPubMedGoogle Scholar
  • 33 Ganesan P, Kumar L, Raina V. et al. Hodgkin’s lymphoma–long-term outcome: an experience from a tertiary care cancer center in North India. Ann Hematol 2011; 90 (10) 1153-1160
    CrossrefPubMedGoogle Scholar
  • 34 Johnson P, Federico M, Kirkwood A. et al. Adapted treatment guided by interim PET-CT scan in advanced Hodgkin’s lymphoma. N Engl J Med 2016; 374 (25) 2419-2429
    CrossrefPubMedGoogle Scholar
  • 35 WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Fourth Edition - WHO - OMS -. http://apps.who.int/bookorders/anglais/detart1.jsp?codlan=1&codcol=70&codcch=4002. Accessed April 15, 2021
  • 36 Olweny CL. Cotswolds modification of the Ann Arbor staging system for Hodgkin’s disease. J Clin Oncol 1990; 8 (09) 1598 http://www.ncbi.nlm.nih.gov/pubmed/2264856 Accessed April 15, 2021
    CrossrefPubMedGoogle Scholar
  • 37 Bonadonna G, Zucali R, Monfardini S, De Lena M, Uslenghi C. Combination chemotherapy of Hodgkin’s disease with Adriamycin, bleomycin, vinblastine, and imidazole carboxamide versus MOPP. Cancer 1975; 36 (01) 252-259 http://www.ncbi.nlm.nih.gov/pubmed/54209 Accessed April 15, 2021
    CrossrefPubMedGoogle Scholar
  • 38 Canellos GP, Anderson JR, Propert KJ. et al. Chemotherapy of advanced Hodgkin’s disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med 1992; 327 (21) 1478-1484
    CrossrefPubMedGoogle Scholar
  • 39 Barrington SF, Qian W, Somer EJ. et al. Concordance between four European centres of PET reporting criteria designed for use in multicentre trials in Hodgkin lymphoma. Eur J Nucl Med Mol Imaging 2010; 37 (10) 1824-1833
    CrossrefPubMedGoogle Scholar
  • 40 Meignan M, Gallamini A, Meignan M, Gallamini A, Haioun C. Report on the First International Workshop on interim-PET scan in lymphoma. Leuk Lymphoma 2009; 50 (08) 1257-1260
    CrossrefPubMedGoogle Scholar
  • 41 Jain S, Kapoor G, Bajpai R. ABVD-based therapy for Hodgkin lymphoma in children and adolescents: lessons learnt in a tertiary care oncology center in a developing country. Pediatr Blood Cancer 2016; 63 (06) 1024-1030
    CrossrefPubMedGoogle Scholar
  • 42 Radhakrishnan V, Dhanushkodi M, Ganesan TS. et al. Pediatric Hodgkin lymphoma treated at cancer institute, Chennai, India: long-term outcome. J Glob Oncol 2016; 3 (05) 545-554
    CrossrefPubMedGoogle Scholar
  • 43 Chandra J, Naithani R, Singh V, Saxena YK, Sharma M, Pemde H. Developing anticancer chemotherapy services in a developing country: Hodgkin lymphoma experience. Pediatr Blood Cancer 2008; 51 (04) 485-488
    CrossrefPubMedGoogle Scholar
  • 44 Laskar S, Gupta T, Vimal S. et al. Consolidation radiation after complete remission in Hodgkin’s disease following six cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy: is there a need?. J Clin Oncol 2004; 22 (01) 62-68
    CrossrefPubMedGoogle Scholar
  • 45 Dinand V, Arya LS. Epidemiology of childhood Hodgkins disease: is it different in developing countries?. Indian Pediatr 2006; 43 (02) 141-147 http://www.ncbi.nlm.nih.gov/pubmed/16528110 Accessed April 15, 2021
    PubMedGoogle Scholar
  • 46 Hoppe RT, Advani RH, Ai WZ. et al. Hodgkin lymphoma version 1.2017, NCCN clinical practice guidelines in oncology. http://www.ncbi.nlm.nih.gov/pubmed/28476741 Accessed April 15, 2021 J Natl Compr Canc Netw 2017; 15 (05) 608-638
    CrossrefPubMedGoogle Scholar
  • 47 Paulino AC, Margolin J, Dreyer Z, Teh BS, Chiang S. Impact of PET-CT on involved field radiotherapy design for pediatric Hodgkin lymphoma. Pediatr Blood Cancer 2012; 58 (06) 860-864
    CrossrefPubMedGoogle Scholar
  • 48 Miller E, Metser U, Avrahami G. et al. Role of 18F-FDG PET/CT in staging and follow-up of lymphoma in pediatric and young adult patients. J Comput Assist Tomogr 2006; 30 (04) 689-694
    CrossrefPubMedGoogle Scholar
  • 49 Montravers F, McNamara D, Landman-Parker J. et al. [(18)F]FDG in childhood lymphoma: clinical utility and impact on management. Eur J Nucl Med Mol Imaging 2002; 29 (09) 1155-1165
    CrossrefPubMedGoogle Scholar
  • 50 Depas G, De Barsy C, Jerusalem G. et al. 18F-FDG PET in children with lymphomas. Eur J Nucl Med Mol Imaging 2005; 32 (01) 31-38
    CrossrefPubMedGoogle Scholar
  • 51 Totadri S, Radhakrishnan V, Ganesan TS. et al. Can radiotherapy be omitted in children with Hodgkin lymphoma who achieve metabolic remission on interim positron emission tomography? experience of a tertiary care cancer referral center. J Glob Oncol 2018; 4 (04) 1-7
    Google Scholar
  • 52 Lopci E, Burnelli R, Ambrosini V. et al. (18)F-FDG PET in Pediatric Lymphomas: a comparison with conventional imaging. Cancer Biother Radiopharm 2008; 23 (06) 681-690
    CrossrefPubMedGoogle Scholar
  • 53 Levine JM, Weiner M, Kelly KM. Routine use of PET scans after completion of therapy in pediatric Hodgkin disease results in a high false positive rate. J Pediatr Hematol Oncol 2006; 28 (11) 711-714
    CrossrefPubMedGoogle Scholar