Primary CNS lymphoma (PCNSL) is a rare and aggressive brain tumour that is uniformly fatal. The rarity of the disease and the poor response to treatment makes it difficult to reach a consensus with regards to treatment options. In this review, the authors have discussed different treatment modalities used in the management of PCNSL including chemotherapy, surgery and radiation, as well as the results of recent clinical trials on treatment options for PCNSL

Ahmed, Syed Ijlal

Jabbar, Adnan

Laghari, Abid

Shamim, Muhammad Shahzad

English

eCommons@AKU

eCommons@AKUSection of Haematology/Oncology Department of MedicineMarch 2018Treatment options for Primary CNS LymphomaAbid LaghariAga Khan University, abid.laghari@aku.eduSyed Ijlal AhmedAga Khan UniversityAdnan JabbarAga Khan University, adnan.jabbar@aku.eduMuhammad Shahzad ShamimAga Khan University, shahzad.shamim@aku.eduFollow this and additional works at: https://ecommons.aku.edu/pakistan_fhs_mc_med_haematol_oncolPart of the Cardiology Commons, Oncology Commons, and the Surgery CommonsRecommended CitationLaghari, A., Ahmed, S. I., Jabbar, A., Shamim, M. (2018). Treatment options for Primary CNS Lymphoma. JPMA. The Journal of thePakistan Medical Association, 68(3), 499-500.Available at: https://ecommons.aku.edu/pakistan_fhs_mc_med_haematol_oncol/40AbstractPrimary CNS lymphoma (PCNSL) is a rare and aggressivebrain tumour that is uniformly fatal. The rarity of thedisease and the poor response to treatment makes itdifficult to reach a consensus with regards to treatmentoptions. In this review, the authors have discusseddifferent treatment modalities used in the managementof PCNSL including chemotherapy, surgery and radiation,as well as the results of recent clinical trials on treatmentoptions for PCNSL.Keywords: Primary CNS Lymphoma, Cerebralmalignancy, Chemotherapy, RadiotherapyIntroductionThe incidence of primary CNS lymphoma (PCNSL) has beenon the rise since the 1970s, even in immuno-competentpatients. The risk is 2-6% in patients with acquiredimmunodeficiency syndrome, and will probably increasewith improving life expectancy in these patients.Transplant patients have a cumulative risk of 1-5% fordeveloping PCNSL. Similarly, patients with congenitalimmune deficiency carry a risk of 4%. Moreover, PCNSL mayalso present as a secondary malignancy. In addition to ageand performance status, which are well known prognosticfactors, symptoms, tumour volume, presence of meningealdissemination and serum LDH level also significantlyinfluence survival in these patients.1 Chemo-radiationtherapy has remained the mainstay of management inpatients with PCNSL and is associated with reasonableefficacy but with high incidence of neurotoxicity. As aconsequence, a difficulty in PCNSL treatment is the choicebetween strategies designed to intensify therapy toimprove the cure rate, versus strategies of treatment de-escalation to avoid severe neurotoxicity.2 In this review, theauthors have discussed the various options for themanagement of PCNSL including chemotherapy, surgeryand radiation therapy, alone or in combination.Review of EvidencePrimary CNS lymphoma was conventionally treated bycorticosteroids and whole brain radiotherapy (WBRT). In1990, Deangelis et al., introduced a protocol that includedintrathecal and systemic methotrexate along with cranialradiotherapy. This vigorous multi-modality regimenshowed improved survival rate over conventionaltherapy.3 Ferreri et al., based their phase II trial onMATILDE regimen which included high dosemethotrexate combined with CNS penetratingchemotherapeutic agents (cytarabine, idarubicin andthiotepa) followed by response tailored radiotherapy.They concluded that this regimen increased the survivalwith reduction in neurological adverse effects of WBRTand intrathecal chemotherapy.4 Follow up of this trial alsosupported the initial findings and suggested animprovement in disease remission at 12 years.5 In anotherstudy, authors concluded that intra-venous nimustine(ACNU), a drug that crosses the blood brain barrier,combined with WBRT improved the survival ofimmunocompetent patients with PCNSL. However, it wasassociated with bone marrow suppression and late onsetneurotoxicity especially in elderly population.6Ghesquieres et al., in a prospective multicenter trial alsoshowed that combination therapy in the form of C5Rprotocol (methotrexate, doxorubicin, vincristine,cyclophosphamide and cytarabine with XRT) is a bettermanagement option for younger immunocompetentpatients but the results were not promising in elderlypopulation because of leukoencephalopathy andcognitive decline.7 Morris et al., also found combinationtherapy as a superior option, and used rituximab,methotrexate, procarbazine, vincristine for induction andthen consolidation with reduced dose of XRT andcytarabine with high response rate, long term diseasecontrol and minimal neurotoxicity.8 Hirono et al.,suggested that stereotactic radiosurgery followed by highdose methotreaxate improves overall survival with thepreservation of daily activities compared to WBRT innewly diagnosed PCNSL.9The recently published trial assessed the tolerability andefficacy of adding rituximab with or without thiotepa tomethotrexate-cytarabine combination therapy (theMATRix regimen), followed by a second randomizationcomparing consolidation with whole-brain radiotherapyor autologous stem cell transplantation in patients withVol. 68, No. 3, March 2018497EVIDENCE BASED NEURO-ONCOLOGYTreatment options for Primary CNS LymphomaAltaf Ali Laghari, Syed Ijlal Ahmed, Adnan Jabbar, Muhammad Shahzad ShamimAga Khan University Hospital, Karachi, Pakistan.Correspondence:Muhammad Shahzad Shamim.Email: shahzad.shamim@aku.eduprimary CNS lymphoma. With the limitations of arandomized phase 2 study design, the IELSG32 trialprovides a high level of evidence supporting the use ofMATRix combination as the new standard chemo-immunotherapy for patients aged up to 70 years withnewly diagnosed primary CNS lymphoma and as thecontrol group for future randomized trials.10 In aprospective observational cohort study, Alvarez-Pinzon etal., compared high dose methotrexate alone withcombination of high dose methotrexate and SRS. Theyconcluded that combination therapy is useful in localcontrol of the newly diagnosed or relapsed cases withoutsignificant neurotoxicity.11Conventionally, the role of surgery is limited to biopsy ofthe lesion for histopathological diagnosis. However,recently Sonabend et al., suggested surgical resection asan alternative treatment option in selected patients. Intheir series, even though the complication rates werecomparable to other intracranial high-grade lesions, theauthors were not able to prove the superiority of surgeryto other therapeutic modalities in the treatment ofPCNSL.12ConclusionThere appear variations in the management of PCNSL andpreferences dictate the use of methotrexate, otherchemotherapeutics, and radiotherapy as managementoptions. Most authors have advocated combination ofchemotherapy and radiotherapy more successful thanany of these treatments alone. The role of stereotacticradiosurgery as co-adjuvant with methotrexate is alsoemerging as useful tool in disease control, better survivaland lesser complications in recent studies. It is ofsignificant value that better survival rates of PCNSLpatients can be obtained by employing multidisciplinarytreatment options.References1. Hayabuchi N, Shibamoto Y, Onizuka Y. Primary central nervoussystem lymphoma in Japan: a nationwide survey. Int J RadiatOncol Biol Phys. 1999; 44: 265-72.2. Ferreri AJ, Marturano E. Primary CNS lymphoma. Best Pract ResClin Haematol. 2012; 25: 119-30.3. DeAngelis LM, Yahalom J, Heinemann MH, Cirrincione C, ThalerHT, Krol G. Primary CNS lymphoma: combined treatment withchemotherapy and radiotherapy. Neurology. 1990; 40: 80-6.4. Ferreri AJ, Dell'Oro S, Foppoli M, Bernardi M, Brandes AA, Tosoni A,et al. MATILDE regimen followed by radiotherapy is an activestrategy against primary CNS lymphomas. Neurology. 2006; 66:1435-8.5. Ferreri AJ, Ciceri F, Brandes AA, Montanari M, Balzarotti M, SpinaM, et al. MATILDE chemotherapy regimen for primary CNSlymphoma: results at a median follow-up of 12 years. Neurology.2014; 82: 1370-3.6. Sonoda Y, Matsumoto K, Kakuto Y, Nishino Y, Kumabe T,Tominaga T, et al. Primary CNS lymphoma treated with combinedintra-arterial ACNU and radiotherapy. Acta Neurochir (Wien).2007; 149: 1183-97. Ghesquieres H, Ferlay C, Sebban C, Perol D, Bosly A, Casasnovas O,et al. Long-term follow-up of an age-adapted C5R protocolfollowed by radiotherapy in 99 newly diagnosed primary CNSlymphomas: a prospective multicentric phase II study of theGroupe d'Etude des Lymphomes de l'Adulte (GELA). Ann Oncol.2010; 21: 842-50.8. Morris PG, Correa DD, Yahalom J, Raizer JJ, Schiff D, Grant B, et al.Rituximab, methotrexate, procarbazine, and vincristine followedby consolidation reduced-dose whole-brain radiotherapy andcytarabine in newly diagnosed primary CNS lymphoma: finalresults and long-term outcome. J Clin Oncol. 2013; 31: 3971-9.9. Hirono S, Iwadate Y, Higuchi Y, Serizawa T, Nagano O, Matsutani T,et al. Stereotactic radiosurgery in combination with up-front high-dose methotrexate as a first-line treatment for newly diagnosedprimary central nervous system lymphoma. J Neurooncol. 2015;123: 237-44.10. Ferreri AJ, Cwynarski K, Pulczynski E, Ponzoni M, Deckert M, PolitiLS, et al. Chemoimmunotherapy with methotrexate, cytarabine,thiotepa, and rituximab (MATRix regimen) in patients withprimary CNS lymphoma: results of the first randomisation of theInternational Extranodal Lymphoma Study Group-32 (IELSG32)phase 2 trial. The Lancet Haematology. 2016; 3: e217-e27.11. Alvarez-Pinzon AM, Wolf AL, Swedberg H, Coy SR, Valerio JE.Primary Central Nervous System Lymphoma (PCNSL): Analysis ofTreatment by Gamma Knife Radiosurgery and Chemotherapy in aProspective, Observational Study. Cureus. 2016; 8: e697.12. Cloney MB, Sonabend AM, Yun J, Yang J, Iwamoto F, Singh S, et al.The safety of resection for primary central nervous systemlymphoma: a single institution retrospective analysis. JNeurooncol. 2017; 132: 189-97.J Pak Med Assoc498 Treatment options for Primary CNS LymphomaFigure: MRI brain T1WI with gadolinum enhancement showing large enhancingabnormal signal intensity lesion in the right occipital lobe involving part of splenium ofcorpus callosum and wrapping the right occipital horn. Later, neuronavigation guidedstereotactic biopsy proved PCNSL.

Treatment options for Primary CNS Lymphoma

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Treatment options for Primary CNS Lymphoma

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