Introduction: Follicular lymphoma（FL) often involves lymph nodes and the bone marrow and is
widely regarded as a systemic and advanced-stage disease when it is diagnosed in more than
two-thirds of patients at initial presentation. Follicular lymphoma Grade 1 or 2 with
indolent histologic characteristics is presently not considered curable in the majority of
patients though it is very sensitive to both chemotherapy and radiotherapy. The policy
treated for patients with stage III and IV FL, which recommended by NCCN, is suggested
regimens, clinical trial or local RT (palliation) based on the previous results that similar
efficacy was obtained after management by chlorambucil single-agent therapy,
polychemotherapy, immunochemotherapy, RT or CMT(RT and Chemotherapy). Patients with
advanced-stage disease tend to have frequent relapses and the interval between subsequent
relapses tends to shorten over time. However, they usually have a relatively long life
expectancy, with a median survival ranging from 6 to 10 years. Try to change the natural
history of FL and have a long term PFS are the goals of treatment for advanced stage FL.
Since the treatment strategy, watch and wait, was managed in Standford in the 1980s, several
prospective randomized trials have failed to demonstrate a survival advantage with immediate
treatment versus a "watch and wait" approach in patients with advanced stage, low tumor
burden FL. Though many systemic therapy options are available for patients with stage III and
IV FL, there is no consensus as to which first-line treatment should be provided to those
patients. "Watch and wait" as a approach is still recommended to the patients even in the
rituximab era. GELA provided the indications for treatment, when the treatment a patient
should be initiated.
The role of traditional RT with or without chemotherapy in advanced stage FL is not definite.
FL is considered to be one of the most radiosensitive tumors. However, a significant
proportion of patients relapse with systemic disease outside of radiation fields and no
difference in OS were observed in advanced patients between RT alone and CMT. The
complications related to traditional RT, including cardiovascular disease and disorders of
blood cell production, were needed to emphasize for those indolent advanced patients who need
frequent palliative management and can long-term survive with NHL. In order to decrease the
late complications after Large-field RT, reduction of irradiation field and smaller
therapeutic doses of radiation were commonly managed.
Many trials that patients with advanced or recurrent FL managed with very low-dose (4Gy)
limited-field RT have shown that high response rates and durable remission can be achieved.
The response rates (either a complete or partial response) reported in previous study that
low-dose involved-field RT (LD-IFRT) is given in 2 daily fractions (2×2 Gy) is 81% to 92%.
The median time to first recurrence was 14 to 15 months. The median overall survival for
patients with a positive response was 41 months. The median time to in-field progression was
21months, and the median time to out-field progression was 8 months. The predominant mode of
tumor cell death after low-dose RT may be by apoptosis.
Two phase III trials have been designed to assess the further role of LD-IFRT. However, the
results have failed to demonstrate the lasting response rate (RR) with LD-IFRT versus in
other approaches. The HOVON 47/EORTC 20013 Intergroup study (www.hovon.nl) which compares
LD-IFRT to chlorambucil chemotherapy in previously untreated FL patients, the main end points
including progression-free survival and quality of life are evaluating. However, the trial
was closed in 2005 after 21 cases included because of the clinical adoption of rituximab. The
age of most eligible patients was older than 65 years. Another trial, Follicular Radiotherapy
Trial (CRUK- FORT), launched recently in the United Kingdom is randomizing patients with FL
needing RT to 24 Gy in 12 fractions versus 4 Gy in 2 fractions as either definitive or
palliative treatment for FL. A significantly lower overall response rate (81% vs 74%) and
2-year local progression-free rate (94% vs 80%) were found in the 4Gy group. Over half of the
patients in the clinic trial were on stage I and stage II. Moreover, the histologies included
many other pathologic subtypes of indolent lymphoma besides follicular Grade 1 or 2.
The role of prognostic factors for treatment efficacy is not consensus. Histology has been
shown to significantly influence response rates. Compared to other subtypes of indolent
lymphoma, the higher response rate of low-dose involved-field radiotherapy (LD-IFRT) as
palliative treatment for indolent lymphoma has been explored in follicular lymphoma.
Age at diagnosis, and prior systemic therapy are more estimated. In the retrospective review
by Girinsky et al. 48 patients with indolent lymphoma treated with LD-IF-RT, factors that
were significantly associated with lack of response including bulky tumor (>5 cm), higher
number of prior chemotherapy regimens, and age＞65 years. Haas et al. reported their
experience of 109 patients with recurrent indolent B-cell NHL treated with LD-IF-RT. Patients
with only one or two lymphoma sites and disease size of ＜5 cm were significantly more likely
to achieve a CR.
The management for advanced FL patients with relapse disease after initial management can be
affected by significant toxicity associated with Chemotherapy and Radiotherapy. The role of
low-dose involved-field radiotherapy (LD-IFRT) as palliative treatment for advanced FL has
been explored. LD-IFRT for selected patients including advanced FL, aged lower than 65 years
and disease size of ＜5 cm may have excellent effection in achieving repeated remissions with
limited associative toxicity and may postpone the need for systemic therapy. The management
is valuable assessed.