CLINICAL NEWS
Cooperative Oncology Group performance status score
(0-1 vs. 2-3), age (<60 vs. >60 years), and disease stage (I
vs. II) to receive either:
• R-CHOP alone (doxorubicin 50 mg/m 2 , cyclophos-
phamide 750 mg/m 2 , vincristine 1.4 mg/m 2 on day 1,
and prednisone 40 mg/m 2 on days 1-5, plus rituximab
375 mg/m 2 on day 1) at 14-day intervals, for 4 con-
secutive cycles (for those without adverse prognostic
factors) or 6 consecutive cycles (for those with ≥1
prognostic factors) (n=165)
• R-CHOP plus RT (40 Gy, in 20 fractions of 2 Gy 5
days per week) four weeks after the last R-CHOP
cycle (n=169)
At baseline, patients underwent positron emission to-
mography (PET) and computed tomography (CT) scans;
response was evaluated via PET/CT scans at two weeks
after the fourth course of R-CHOP. A total of 319 patients
were evaluable for response (159 in the R-CHOP group,
and 160 in the R-CHOP plus RT group).
The median relative dose-intensity of cytotoxic drugs
was 97 percent (95% CI 97-98) of the planned sched-
ule. There was a median of four days of delay between
cycles four and five, “mainly due to the time needed for
response assessment by PET,” the authors wrote. The
median time between R-CHOP and first day of RT was 36
days (range = 10-132 days).
During R-CHOP, 66 episodes of febrile neutropenia
were reported in 50 patients. Four severe infections and one
death due to septic shock occurred. Eighteen patients (6%)
required red blood cell transfusions. After RT, two patients
reported grade 3 mucositis and one reported jaw radione-
crosis. A few severe (n=5) and moderate
(n=8) cardiac toxicities were reported.
Most patients (n=281; 88%) achieved
a complete response (CR) after four
treatment cycles, including 137 in the
R-CHOP group and 144 in the R-CHOP
plus RT group. Another 38 patients
(12%) achieved a partial response (PR;
see TABLE 1 on page 50).
After a median follow-up of 64 months
(range = 24-132 months), the five-year
event-free survival (EFS; primary end-
point) was not statistically significant
different between the two treatment arms:
89±2.9% for R-CHOP alone and 92±2.4%
for R-CHOP plus RT (hazard ratio [HR] =
0.61; 95% CI 0.3-1.2; p=0.18).
Five-year overall survival (OS; second-
ary endpoint) also was similar between the
groups: 92±2.5% versus 96±1.7% (HR=0.62;
95% CI 0.3-1.5; p=0.28). (The study was
powered to detect differences in OS to an
upper limit of 8%.)
R-CHOP alone remained non-inferior
to R-CHOP plus RT whether patients
achieved a CR or PR, the authors added,
and EFS was significantly impacted by
patient mIPI score (HR=2.8; 95% CI 0.6-
14.1; p=0.04).
“In this selected group of limited-stage
DLBCL, the relapse rate was very low (23
patients; 13 in the R-CHOP alone arm
and 8 in the R-CHOP plus RT cohort),
with a median time of 21 months (range
= 4-93 months),” the authors reported.
Twenty-one deaths occurred (12 in the
R-CHOP arm and 9 in the R-CHOP plus
RT arm), and were related to disease pro-
gression (n=11), secondary malignancies
(n=3), accident (n=2), stroke (n=1), and
late-onset infection (n=1); the other three
deaths had unknown causes.
“This trial prompts [us] to recommend
that patients with non-bulky limited-
stage DLBCL who reach CR based on
PET evaluation after four or six R-CHOP
cycles should be spared additional RT,
thus avoiding radiation-related toxicity,”
the authors concluded. “PET could help to
deliver RT to the minority of patients with
residual PET-positive tumors.” They added
that the ongoing 09-1B LYSA (Lymphoma
Study Association) trial is investigating
whether patients with adverse prognostic
factors require six cycles of R-CHOP, or
if they can safely and effectively reduce
R-CHOP to four cycles.
The study is limited in that it only
included patients with non-bulky tumors,
so it may not be generalizable to the entire
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