Skip to main content

Advertisement

SpringerLink
Log in

Impact of acute hematological toxicity on treatment interruptions during cranio-spinal irradiation in medulloblastoma: a tertiary care institute experience

  • Clinical Study
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

To analyze treatment interruptions due to acute hematological toxicity in patients of medulloblastoma receiving cranio-spinal irradiation (CSI). Prospectively collected data from case records of 52 patients of medulloblastoma treated between 2011 and 2014 was evaluated. Blood counts were monitored twice a week during CSI. Spinal irradiation was interrupted for patients with ≥grade 2 hematological toxicity and resumed after recovery to grade 1 level (TLC >3000; platelet count >75,000). Treatment interruptions and hematological toxicity were analyzed. Median age was 11 years. All patients received adjuvant CSI of 36 Gy, followed by boost of 18 Gy to posterior fossa, at 1.8 Gy per fraction. Concurrent chemotherapy was not given. Adjuvant chemotherapy was given after CSI for high risk patients. Spinal fields were interrupted in 73.1% of patients. Cause of first interruption was leucopenia in 92.1%, thrombocytopenia in 2.6%, and both in 5.3%. Median number of fractions at first interruption was 8, with 25% of interruptions in first week. Median duration for hematological recovery after nadir was 5 days for leucopenia and 3 days for thrombocytopenia. Half of the patients had at least 2 interruptions, and 19% subsequently developed grade 3 toxicity. On multivariate analysis, significant correlation with duration of delay was observed for pre-treatment haemoglobin, number of fractions at first interruption, grade and duration of recovery of leucopenia. Acute hematological toxicity with CSI is frequently under-reported. Patients with low pre-treatment hemoglobin, early onset leucopenia, profound leucopenia and prolonged recovery times are at a higher risk of having protracted courses of irradiation. Frequent monitoring of blood counts and timely interruption of spinal fields of irradiation at grade 2 level of hematological toxicity minimizes the risk of grade 3 and grade 4 toxicity, while reducing the interruptions in irradiation of the gross tumour bed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Halperin EC, Perez CA, Brady LW (2008) Perez and Brady’s principles and practice of radiation oncology. Lippincott Williams & Wilkins, Philadelphia

    Google Scholar 

  2. Bailey CC, Gnekow A, Wellek S, Jones M, Round C, Brown J, Phillips A, Neidhardt MK (1995) Prospective randomised trial of chemotherapy given before radiotherapy in childhood medulloblastoma. International Society of Paediatric Oncology (SIOP) and the (German) Society of Paediatric Oncology (GPO): SIOP II. Med Pediatr Oncol 25(3):166–178

    Article  CAS  PubMed  Google Scholar 

  3. Thomas PR, Deutsch M, Kepner JL, Boyett JM, Krischer J, Aronin P, Albright L, Allen JC, Packer RJ, Linggood R, Mulhern R (2000) Low-stage medulloblastoma: final analysis of trial comparing standard-dose with reduced-dose neuraxis irradiation. J Clin Oncol 18(16):3004–3011

    Article  CAS  PubMed  Google Scholar 

  4. Bouffet E, Bernard JL, Frappaz D, Gentet JC, Roche H, Tron P, Carrie C, Raybaud C, Joannard A, Lapras C, Choux M (1992) M4 protocol for cerebellar medulloblastoma: supratentorial radiotherapy may not be avoided. Int J Radiat Oncol* Biol* Phys 24(1):79–85

    Article  CAS  Google Scholar 

  5. Carrie C, Muracciole X, Gomez F, Habrand JL, Benhassel M, Mege M, Mahé M, Quetin P, Maire JP, Soum F, Baron MH (2005) Conformal radiotherapy, reduced boost volume, hyperfractionated radiotherapy, and online quality control in standard-risk medulloblastoma without chemotherapy: results of the French M-SFOP 98 protocol. Int J Radiat Oncol* Biol* Phys 63(3):711–716

    Article  Google Scholar 

  6. Ellison DW, Kocak M, Dalton J, Megahed H, Lusher ME, Ryan SL, Zhao W, Nicholson SL, Taylor RE, Bailey S, Clifford SC (2010) Definition of disease-risk stratification groups in childhood medulloblastoma using combined clinical, pathologic, and molecular variables. J Clin Oncol 29:1400–1407

    Google Scholar 

  7. Packer RJ, Goldwein J, Nicholson HS, Vezina LG, Allen JC, Ris MD, Muraszko K, Rorke LB, Wara WM, Cohen BH, Boyett JM (1999) Treatment of children with medulloblastomas with reduced-dose craniospinal radiation therapy and adjuvant chemotherapy: a Children’s Cancer Group Study. J Clin Oncol 17(7):2127–2136

    Article  CAS  PubMed  Google Scholar 

  8. Packer RJ, Zhou T, Holmes E, Vezina G, Gajjar A (2012) Survival and secondary tumors in children with medulloblastoma receiving radiotherapy and adjuvant chemotherapy: results of children’s oncology group trial A9961. Neuro-oncology 15:97–103

    Google Scholar 

  9. Mulhern RK, Kepner JL, Thomas PR, Armstrong FD, Friedman HS, Kun LE (1998) Neuropsychologic functioning of survivors of childhood medulloblastoma randomized to receive conventional or reduced-dose craniospinal irradiation: a Pediatric Oncology Group study. J Clin Oncol 16(5):1723–1728

    Article  CAS  PubMed  Google Scholar 

  10. Taylor RE, Bailey CC, Robinson K, Weston CL, Ellison D, Ironside J, Lucraft H, Gilbertson R, Tait DM, Walker DA, Pizer BL (2003) Results of a randomized study of preradiation chemotherapy versus radiotherapy alone for nonmetastatic medulloblastoma: the International Society of Paediatric Oncology/United Kingdom Children’s Cancer Study Group PNET-3 Study. J Clin Oncol 21(8):1581–1591

    Article  CAS  PubMed  Google Scholar 

  11. Paulino AC, Wen BC, Mayr NA, Tannous R, Loew TW, Goldman FD, Meeks SL, Ryken TC, Buatti JM (2003) Protracted radiotherapy treatment duration in medulloblastoma. Am J Clin Oncol 26(1):55–59

    Article  PubMed  Google Scholar 

  12. Cox JD, Stetz J, Pajak TF (1995) Toxicity criteria of the radiation therapy oncology group (RTOG) and the European organization for research and treatment of cancer (EORTC). Int J Radiat Oncol* Biol* Phys 31(5):1341–1346

    Article  CAS  Google Scholar 

  13. Ellis RE (1961) The distribution of active bone marrow in the adult. Phys Med Biol 5(3):255

    Article  CAS  PubMed  Google Scholar 

  14. Mauch P, Constine L, Greenberger J, Knospe W, Sullivan J, Liesveld JL, Deeg HJ (1995) Hematopoietic stem cell compartment: acute and late effects of radiation therapy and chemotherapy. Int J Radiat Oncol* Biol* Phys 31(5):1319–1339

    Article  CAS  Google Scholar 

  15. Mell LK, Kochanski JD, Roeske JC, Haslam JJ, Mehta N, Yamada SD, Hurteau JA, Collins YC, Lengyel E, Mundt AJ (2006) Dosimetric predictors of acute hematologic toxicity in cervical cancer patients treated with concurrent cisplatin and intensity-modulated pelvic radiotherapy. Int J Radiat Oncol* Biol* Phys 66(5):1356–1365

    Article  Google Scholar 

  16. Ahmed RS, Kim RY, Duan J, Meleth S, Jennifer F, Fiveash JB (2004) IMRT dose escalation for positive para-aortic lymph nodes in patients with locally advanced cervical cancer while reducing dose to bone marrow and other organs at risk. Int J Radiat Oncol* Biol* Phys 60(2):505–512

    Article  Google Scholar 

  17. Lujan AE, Mundt AJ, Yamada SD, Rotmensch J, Roeske JC (2003) Intensity-modulated radiotherapy as a means of reducing dose to bone marrow in gynecologic patients receiving whole pelvic radiotherapy. Int J Radiat Oncol* Biol* Phys 57(2):516–521

    Article  Google Scholar 

  18. Jefferies S, Rajan B, Ashley S, Traish D, Brada M (1998) Haematological toxicity of cranio-spinal irradiation. Radiother Oncol 48(1):23–27

    Article  CAS  PubMed  Google Scholar 

  19. Aghili M, Kazemian A, Meysami AP (2005) Hematological toxicities and treatment interruption due to craniospinal irradiation. Iran J Radiat Res (Print) 3(2):95–99

    Google Scholar 

  20. Kortmann RD, Kühl J, Timmermann B, Mittler U, Urban C, Budach V, Richter E, Willich N, Flentje M, Berthold F, Slavc I (2000) Postoperative neoadjuvant chemotherapy before radiotherapy as compared to immediate radiotherapy followed by maintenance chemotherapy in the treatment of medulloblastoma in childhood: results of the German prospective randomized trial HIT’91. Int J Radiat Oncol* Biol* Phys 46(2):269–279

    Article  CAS  Google Scholar 

  21. Chang EL, Allen P, Wu C, Ater J, Kuttesch J, Maor MH (2002) Acute toxicity and treatment interruption related to electron and photon craniospinal irradiation in pediatric patients treated at the University of Texas MD Anderson Cancer Center. Int J Radiat Oncol* Biol* Phys 52(4):1008–1016

    Article  Google Scholar 

  22. Cox MC, Kusters JM, Gidding CE, Schieving JH, van Lindert EJ, Kaanders JH, Janssens GO (2015) Acute toxicity profile of craniospinal irradiation with intensity-modulated radiation therapy in children with medulloblastoma: a prospective analysis. Radiat Oncol 10(1):1

    Article  Google Scholar 

  23. Kusters JM, Louwe RJ, van Kollenburg PG, Kunze-Busch MC, Gidding CE, van Lindert EJ, Kaanders JH, Janssens GO (2011) Optimal normal tissue sparing in craniospinal axis irradiation using IMRT with daily intrafractionally modulated junction(s). Int J Radiat Oncol* Biol* Phys 81(5):1405–1414

    Article  Google Scholar 

  24. Guerra JL, Marrone I, Jaen J, Bruna M, Sole C, Sanchez-Reyes A, Rivin E, Ortiz MJ, Calvo F, Matute R (2014) Outcome and toxicity using helical tomotherapy for craniospinal irradiation in pediatric medulloblastoma. Clin Translat Oncol 16(1):96–101

    Article  Google Scholar 

  25. Brown AP, Barney CL, Grosshans DR, McAleer MF, De Groot JF, Puduvalli VK, Tucker SL, Crawford CN, Khan M, Khatua S, Gilbert MR (2013) Proton beam craniospinal irradiation reduces acute toxicity for adults with medulloblastoma. Int J Radiat Oncol* Biol* Phys 86(2):277–284

    Article  Google Scholar 

  26. Barney CL, Brown AP, Grosshans DR, McAleer MF, de Groot JF, Puduvalli V, Tucker SL, Crawford CN, Gilbert MR, Brown PD, Mahajan A (2014) Technique, outcomes, and acute toxicities in adults treated with proton beam craniospinal irradiation. Neuro-oncology 16(2):303–309

    Article  CAS  PubMed  Google Scholar 

  27. Dinh J, Stoker J, Georges RH, Sahoo N, Zhu XR, Rath S, Mahajan A, Grosshans DR (2013) Comparison of proton therapy techniques for treatment of the whole brain as a component of craniospinal radiation. Radiat Oncol 8(1):1

    Article  Google Scholar 

  28. Mac Manus MP, Clarke J, McCormick D, Abram WP (1993) Use of recombinant granulocyte-colony stimulating factor to treat neutropenia occurring during craniospinal irradiation. Int J Radiat Oncol* Biol* Phys 26(5):845–850

    Article  CAS  Google Scholar 

  29. Mac Manus MP, McCormick D, Trimble A, Abram WP (1995) Value of granulocyte colony stimulating factor in radiotherapy induced neutropenia: clinical and laboratory studies. Eur J Cancer 31(3):302–307

    Article  Google Scholar 

  30. Marks LB, Friedman HS, Kurtzberg J, Oakes WJ, Hockenberger BM (1992) Reversal of radiation-induced neutropenia by granulocyte colony-stimulating factor. Med Pediatr Oncol 20(3):240–242

    Article  CAS  PubMed  Google Scholar 

  31. Lyman GH, Kuderer NM, Djulbegovic B (2002) Prophylactic granulocyte colony-stimulating factor in patients receiving dose-intensive cancer chemotherapy: a meta-analysis. Am J Med 112(5):406–411

    Article  CAS  PubMed  Google Scholar 

  32. Clark OA, Lyman GH, Castro AA, Clark LG, Djulbegovic B (2005) Colony-stimulating factors for chemotherapy-induced febrile neutropenia: a meta-analysis of randomized controlled trials. J Clin Oncol 23(18):4198–4214

    Article  CAS  PubMed  Google Scholar 

  33. Sung L, Nathan PC, Alibhai SM, Tomlinson GA, Beyene J (2007) Meta-analysis: effect of prophylactic hematopoietic colony-stimulating factors on mortality and outcomes of infection. Ann Intern Med 147(6):400–411

    Article  PubMed  Google Scholar 

  34. Janssens P, Mitine C, Beauduin M, Scalliet P (1994) Is there potential for granulocyte or granulocyte-macrophage colony stimulating factors in radiotherapy?. Eur J Cancer 30(5):642–645

    Article  Google Scholar 

  35. National Comprehensive Cancer Network (2014) NCCN clinical practice guidelines in oncology (NCCN Guidelines): Myeloid growth factors (version 2.2014)

  36. Crawford J, Caserta C, Roila F, ESMO Guidelines Working Group (2010) Hematopoietic growth factors: ESMO clinical practice guidelines for the applications. Ann Oncol 21(suppl 5):v248-51

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiotherapy & Oncology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

    Narendra Kumar, Raviteja Miriyala, Pragyat Thakur, Renu Madan, Budhi Yadav & Ankita Gupta

  2. Department of Neurosurgery, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

    Pravin Salunke

Authors
  1. Narendra Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Raviteja Miriyala
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pragyat Thakur
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Renu Madan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pravin Salunke
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Budhi Yadav
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ankita Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Narendra Kumar.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kumar, N., Miriyala, R., Thakur, P. et al. Impact of acute hematological toxicity on treatment interruptions during cranio-spinal irradiation in medulloblastoma: a tertiary care institute experience. J Neurooncol 134, 309–315 (2017). https://doi.org/10.1007/s11060-017-2524-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-017-2524-7

Keywords

Search

Navigation