Reversal of cranial nerve dysfunction with radiation therapy in adults with lymphoma and leukemia

doi:10.1016/0360-3016(90)90555-X

International Journal of Radiation OncologyBiologyPhysics

Volume 19, Issue 2, August 1990, Pages 439-444

https://doi.org/10.1016/0360-3016(90)90555-X Get rights and content

Abstract

Twenty patients with leukemic (8) or lymphomatous (12) meningitis and cranial nerve palsies were treated with cranial irradiation at Memorial Sloan-Kettering Cancer Center from June 1987 through December 1988. The diagnosis of malignant meningitis was confirmed by malignant or `suspicious' cerebrospinal fluid cytology in $1320$ patients. The 6th and 7th cranial nerves were most commonly involved. Multiple nerve involvement was present in $1120$ patients, for a total of 42 nerves affected. Treatment consisted of whole brain irradiation to a median dose of 2400 cGy (range: 1000–3000) at 200–300 cGy per fraction. Median survival was 7 months. Forty of 42 nerves improved, for an actuarial response rate of 95% at 3 months. The complete response rate was 44% and was better for patients with lymphoma than for those with leukemia (72% vs 19%, p = 0.04). Delaying initiation of irradiation more than 3 days after the onset of symptoms did not affect the ultimate response rate, but slightly increased the median time to response (9 days vs 14 days, p = 0.1). Radiation therapy is an effective means of reversing cranial nerve dysfunction in leukemia and lymphoma. Higher doses may be needed to increase the rate of complete response.

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Craniospinal irradiation prior to stem cell transplant for hematologic malignancies with CNS involvement: Effectiveness and toxicity after photon or proton treatment
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Citation Excerpt :
Radiation therapy is increasingly recognized as efficacious for the treatment of central nervous system (CNS) disease in hematologic malignancy patients, primarily leukemia.1 Although the natural history of leukemia/lymphoma has been known to include CNS disease,2,3 recent advances in therapy leading to overall improved hematologic malignancy outcomes have increased the rates of patients presenting with this therapeutic challenge, primarily from poor CNS penetrance of cytotoxic and targeted therapy agents.4,5 Although leukemia and lymphoma involving the CNS is generally associated with poor prognosis,4-6 a prior study demonstrated that whole brain or craniospinal irradiation (CSI) still conferred a 12-month CNS progression-free survival rate of 77% in patients affected with acute leukemia.1
Craniospinal irradiation (CSI) improves local control of leukemia/lymphoma with central nervous system (CNS) involvement; however, for adult patients anticipating stem cell transplant (SCT), cumulative treatment toxicity is a major concern. We evaluated toxicities and outcomes for patients receiving proton or photon CSI before SCT.
We identified 37 consecutive leukemia/lymphoma patients with CNS involvement who received CSI before SCT at our institution. Photon versus proton toxicities during CSI, transplant, and through 100 days posttransplant were compared using Fisher exact and Wilcoxon rank sum tests. Long-term neurotoxicity, disease response, and overall survival were analyzed.
Thirty-seven patients (23 photon, 14 proton) underwent CSI for CNS involvement of acute lymphoblastic leukemia (49%), acute myeloblastic leukemia (22%), chronic lymphocytic leukemia (3%), chronic myelocytic leukemia (14%), lymphoma (11%), and myeloma (3%). CSI was used for consolidation (30 patients, 81%) and gross disease treatment (7 patients, 19%). Median radiation dose (interquartile range) was 24 Gy (23.4-24) for photons and 21.8 Gy (21.3-23.6) for protons (P = .03). Proton CSI was associated with lower rates of Radiation Therapy Oncology Group grade 1-3 mucositis during CSI (7% vs 44%, P = .03): 1 grade 3 with protons versus 5 grade 1, 3 grade 2, and 2 grade 3 with photons. During CSI, other toxicities (infection, gastrointestinal symptoms) did not differ. Allogeneic stem cell transplant (SCT) was used in 95% of patients, with 53% of patients in remission before SCT. Myeloablative conditioning was used for 76%. During SCT admission and 100 days post-SCT, toxicities did not differ by CSI technique. Successful engraftment occurred in 95% of patients (P = .67). Progression or death occurred for 47% of patients, with only 1 CNS relapse.
In our cohort, CSI offered excellent local control for CNS-involved hematologic malignancies in the pre-SCT setting. Acute mucositis occurred less frequently with proton CSI with comparable peritransplant/long-term toxicity profile, suggesting the need to further explore the benefit/toxicity profile of this technique.
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With the increasing number of patients who undergo multiple salvage regimens and thus survive multiple systemic relapses, CNS relapse and its treatment have emerged as important components of the disease course (7-10). Previous work has been done to clarify the symptoms of CNS leukemia and the benefit of RT; however, little information exists regarding extent of the optimal RT field (11-14). To control CNS disease, RT can be focused on the base of skull, the whole brain, or the entire craniospinal axis.
To determine the benefit of radiation therapy (RT) in resolution of neurologic symptoms and deficits and whether the type of RT fields influences central nervous system (CNS) control in adults with CNS leukemia.
A total of 163 adults from 1996 to 2012 were retrospectively analyzed. Potential associations between use of radiation and outcome were investigated by univariate and multivariate analysis.
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Improvement or resolution of symptoms occurred in two thirds of deficits after RT. Comprehensive radiation to the WB or CS seems to offer a better outcome, especially in isolated CNS involvement.
Leptomeningeal Metastasis
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Focal RT has been successful at relieving pain, focal weakness, sensory loss, bowel/bladder dysfunction, focal seizures, cranial nerve palsies, and CSF flow abnormalities.122 If RT is delivered early enough and appropriately directed, neurologic abnormalities can sometimes be reversed.121,123 In one study, over two-thirds of patients receiving RT experienced regression of neurological symptoms either during or within days after RT was completed.124
Primary meningeal lymphoma of T-cell origin: A rare presentation of primary central nervous system lymphomas
2007, Clinical Lymphoma and Myeloma
Primary meningeal lymphoma is a rare clinical entity. Central nervous system infiltration by systemic lymphoma should always be excluded. Diagnosis can be difficult, and prognosis is usually poor. Most are of B-cell origin. We present the case of a young man with a primary meningeal lymphoma of T-cell origin. He was treated with systemic chemotherapy with high-dose methotrexate and cytarabine and intraventricular chemotherapy. He had a clinical improvement and a complete remission, with a long overall survival. There is no standard treatment for this rare disease. Traditionally, treatment has been based in craniospinal radiation therapy and intrathecal chemotherapy, with poor overall results. More recently, systemic chemotherapy with high-dose methotrexate has been advocated, which could avoid the long-term toxicity of craniospinal radiation therapy, and could improve the prognosis of these patients.
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^☆: Presented at the American Society for Therapeutic Radiation Oncology, San Francisco, CA, October 1989.

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Brief communicationReversal of cranial nerve dysfunction with radiation therapy in adults with lymphoma and leukemia☆

Abstract

Blood

The importance of isolated central nervous system relapse in children with acute lymphoblastic leukemia

J. Clin. Oncol.

Nonparametric estimation from incomplete observations

J. Am. Stat. Assoc.

Comparison of maintenance treatment regimens for first central nervous system relapse in children with acute lymphocytic leukemia

Cancer

Brief communication
Reversal of cranial nerve dysfunction with radiation therapy in adults with lymphoma and leukemia☆