"Low-Dose Involved Field Radiotherapy Induces Rapid and Lasting Remissions Without Significant Toxicity in B-Cell Lymphoma: Presented at ICML"
By Chris Berrie
LUGANO, SWITZERLAND -- June 10, 2005 -- Low-dose involved field radiotherapy (LD-IF-RT) using up to 4 Gy induces an excellent overall response rate (ORR) in patients with recurrent and/or chemotherapy-refractory B-cell lymphoma, according to a joint phase 2 trial.
Rick L. Haas, MD, principal investigator and radiation oncologist, department of radiotherapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands, reported the findings here June 10[th at the 9th International Conference on Malignant Lymphoma (ICML).
Earlier work demonstrated the excellent local disease control without significant toxicity of LD-IF-RT up to 4 Gy in patients with follicular lymphoma (FL). Other studies also demonstrated that FL is one of the most radiosensitive tumours.
"We thought that there were other indolent lymphomas that show multiple relapses during their clinical course, and so we asked ourselves whether this regimen could be provided to those patients as well," Dr. Haas said.
Therefore, Dr. Haas and colleagues conducted a joint study with the Bernard Verbeeten Institute, Tilberg, The Netherlands, to compare the efficacy of LD-IF-RT in patients with FL or other lymphomas.
Between 1997 and 2004, the researchers recruited 200 patients with a median age of 61 years (range, 31-93 years; 51% male), a median time since primary diagnosis of 49 months (range, 3-358 months), and a median number of prior chemotherapy and/or radiotherapy regimens of 2 (range, 1-11).
Bulky disease, defined as tumours 5 cm or greater in diameter, were present in 122 patients, and the range of disease pathologies was: FL (n = 123), small/chronic lymphocytic lymphomas (SLL/CLL; n = 23), marginal zone lymphomas (n = 18), mantle cell lymphomas (n = 17), diffuse large B-cell lymphomas (n = 13), and lymphocyte predominant Hodgkin's lymphomas (n = 6).
As a single population, LD-IF-RT resulted in 56% complete response (CR; n = 111), with a 90% ORR. These results were independent of patient age, sex, intensity of prior treatment, time since diagnosis, and tumour histology or size. Toxicity was either very mild or absent.
Median time to disease progression overall was 15 months, with a median time to local progression exceeding 36 months.
After cases were divided according to whether they were indolent lymphomas or follicular, the researchers found that subjects responded equally well to the treatment, with CR of 58% versus 60%, respectively; and ORR of 92% and 93%, respectively.
Aggressive subtypes (mantle cell and diffuse large-cell lymphomas; n = 30) achieved significantly lower rates of CR (37% vs 60% for FL; P =.02) and ORR (80% vs 93%; P =.04).
When broken down into individual groups, the ORR remained over 90% for FL (93%), SLL/CLL (91%), and marginal zone lymphomas (95%), with around 80% for lymphocyte-predominant Hodgkin's lymphomas (83%) and mantle cell lymphomas (82%). The DLCL group showed the lowest ORR, at 76%.
Median times to disease progression and to local progression were reduced in the aggressive subtypes (9 months, 19 months, respectively). The indolent subtypes (18 months, 24 months, respectively) were similar to FL (19 months, > 36 months, respectively).
In looking to the future, Dr Haas indicated that they now have biopsy samples from a number of these patients obtained before and after radiation treatments, and intend to use microarray analysis to determine which pathways provide this effective response.
Dr Haas considers that this fast, cheap, nontoxic, and multiply repeatable treatment with LD-IF-RT up to 4 Gy should be considered in the management of B-cell lymphoma patients with recurrent and/or chemotherapy refractory disease. His take-home message was, "Never forget low-dose radiation in haematology."
[Study title: Four Gy Involved Field Radiotherapy Induces Rapid and Lasting Remissions Without Significant Toxicity in 200 B-Cell Lymphoma Patients. Abstract 242]
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