Amanda

Cihon
Appl Onc II
4/22/2013
Hodgkins Lymphoma Treatment in the Elderly Population

Of all Hodgkins lymphoma (HL) patients 20% are older patients

greater than sixty years old.1(1522) The standard care for these patients is
chemotherapy with ABVD (doxorubicin, bleomycin, vinblastine, decarbazine)
but not much is known about treatment with ABVD or other forms of
treatment for the older age range. For that reason it is necessary to study
new forms of treatment that may better suit the elderly generation with HL.
The following three journals will compare different treatment methods for the
elderly with advance stage and early stage HL, all agreeing that more
research needs to be done in order to find better treatment options.
The German Hodgkin Study Group (GHSG) created two trials, HD10 and
HD11, which compared the results of methods of delivery with ABVD with
radiation therapy and BEACOOP (bleomycin, etoposide, doxorybicin,
cyclophosphamide, vincristine, procarbazine, prednisone) with radiation
therapy. The GHSG used these two trials to compare the feasibility, efficacy,
and safety of four trial groups in patients 60-75 years old to the effects seen
in younger patients. Patients with first diagnosis of favorable or unfavorable
early stage HL were enrolled and their results were compared.
In the GHSG HD10 and HD11 trials 1,299 patients were enrolled. Of
that 1,299, 117 were greater than 60 years old and were assigned to one of
the trial groups. The different groups were four cycles of ABVD followed by
1

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Cihon
Appl Onc II
4/22/2013

20 or 30 Gy of involved field radiotherapy (IFRT), two cycles of ABVD followed

by IFRT, or four cycles of BEACOOP followed by IFRT.1(p1523) Feasibility, safety,
and efficacy were assessed in each group. Feasibility was evaluated
according to protocol adherence, safety by toxicity, and treatment associated
deaths.1(p1523) For feasibility 86% of older patients in the four cycle ABVD
group received treatment according to protocol, dropping out of protocol due
to toxicity. The older population also had lower relative dose intensity (RDI)
than younger due to dose reductions and treatment delays. The mean RDI
for older patients was 83% with only 59% of patients achieving at least 80%
of treatment compared to 85% of younger having an RDI of 80%. Treatment
delay was 2.2 weeks in the older and 1.2 weeks in the younger. To measure
the amount of safety, toxicity and treatment associated deaths were used.
There were 68% of older who had toxicities of WHO grade 3 and 4 which
included grade 4 for 18%. Six patients (5%) died as a result of acute
toxicity.1(p1525) Efficacy was measured by response rates, overall survival (OS),
and progression free survival.1(p1523) It was attained during the final restaging
three months after the end of therapy and 89% of older patients had
complete response (CR). With four cycles of ABVD the CR rate was
significantly lower in older patients than younger. The over survival (OS) and
progression free survival (PFS) of five years was estimated at 81% for the
older.1(p1526) When taking account for all of the results and study found the

Amanda
Cihon
Appl Onc II
4/22/2013

feasibility, safety, and efficacy were lower for older patients than for
younger.
The GHSG HD10 and HD11 trials were one of the few trials on ABVD in
older patients. They had some limitations that affected the reliability. The
analysis lacked a comprehensive geriatric assessment and a restriction to
early stage patients. Because of these limitations, the results only held true
for a selected part of the older population and only allowed for indirect
conclusions on the general population with HL.1(p1528) In order to fully see the
effects in older patients they would need a higher age range and also need
to test on advance stage patients.
This analysis challenged the standard treatment of early stage HL in
older patients with ABVD by showing that it has feasibility and treatment
related mortality in patients aged 60-75. By showing that the standard
treatment needs more work makes it even more necessary to study new
treatment strategies that better suit the specific needs of older patients with
early stage HL.1(p1528)
The German Hodgkin Study Group also held the first prospectively
randomized multicenter study for older HL patients called HD9elderly.2(p128) For
this randomized trial, two treatment methods were compared for treatment
of advanced stage HL, BEACOOP baseline and COPP-ABVD
(cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin,
3

Amanda
Cihon
Appl Onc II
4/22/2013

bleomycin, vinblastine, decarbazine). BEACOOP baseline showed an

improvement in the younger patients therefor was chosen to be tested on
the older population against the standard COPP-ABVD method. Patients in the
HD9elderly trial were randomized into two treatment groups to try and develop
a new way to treat advanced stage HL.
The HD9elderly trial consisted of 68 patients between the ages of 66-75.
To be considered advanced stage, patients had to be stage IIB with large
mediastinal mass and/or extranodal involvement and/or spleen involvement,
stage III, or stage IV. Of the 68 patients, 26 received 8 alternating courses of
COPP-ABVD and 42 received 8 courses of BEACOPP baseline.2(p125,126) Success
of the trial was determined by restaging after four and eight cycles of chemo
or a final restaging was done 4-8 weeks post radiation therapy if radiation
therapy was given.2(p126) The trial was to compare the feasibility, toxicity, and
efficacy of the standard COPP-ABVD treatment to that of the more aggressive
BEACOPP baseline regime in elderly patients.2(p125)
Out of the 68 patients in the trial, 41 received full planned number of
treatment cycles with a greater percentage receiving the full amount of
COPP-ABVD cycles. Early termination during chemo or before radiation
therapy occurred in 50% of both COPP-ABVD and BEACOPP baseline. Many
patients finished BEACOPP baseline prematurely due to high toxicity.2(p126)
Severe toxicity of WHO grade IV occurred in 87% of patients being treated

Amanda
Cihon
Appl Onc II
4/22/2013

with BEACOPP and 44% of COPP-ABVD. There were also 11 toxic related
deaths of which most came from the BEACOPP baseline group.2(p127) Complete
responses (CR) occurred in 76% of all patients and showed no difference
between groups. After a follow up of a median of 80 months, 11 patients
relapsed and an overall 37 patients were deceased.2(p128)
The HD9elderly exhibited that COPP-ABVD and BEACOPP had similar
success in treating HL with toxicity being significantly higher with BEACOPP.
The study was carried out well besides the low amount of participants.
Having only 68 patients in the trial does not necessarily mean that it can
count for all the elderly. Having a low sample size affects the validity of the
study. In order to improve it, the study would need to be carried out with a
larger sample size in order to say that it accounts for elderly HL patients as a
whole.
For older patients with advanced stage HL the outcome is pretty dismal
no matter what form of treatment. With different treatments though, side
effects can be much less harsh. HD9elderly tried to find a more effective
treatment with BEACOPP baseline since it had worked with younger patients.
The BEACOPP treatment failed in the elderly due to their different biological
responses to chemo. There was no difference in overall response and early
progression rates and no difference in treatment outcome between the two
groups. The difference occurred in acute toxicity and toxic deaths that

Amanda
Cihon
Appl Onc II
4/22/2013

elderly patients suffered in the BEACOPP baseline group.2(p128) The GHSG

HD9elderly trial demonstrated that intensified chemo regimes are effective on
the elderly but causes significantly more toxicity leading to treatment related
mortality. Therefore, it is unable to be considered as an alternate form of
treatment. The study also proved that more research needs to be done on
treatments of advanced stage HL elderly patients.2(p130)
The first two trials have showed the high toxicity rate chemo regimes
have on the older population of HL patients with early and late stage
disease. Treating with radiation therapy alone can decrease some of the
toxicities caused by chemo or combined modality treatment. A populationbased cohort study was conducted to see if radiation therapy could be
considered as a first line treatment for newly diagnosed early stage HL in
elderly patients.
The goal of the study was to evaluate the relapse rate, outcomes, and
predictors of prognosis in early stage elderly HL patients.3(p1290) There were
308 patients included in the study, 22% of which were greater than or at age
60 years old. All patients were referred to, seen, and treated with radiation
therapy at one center limiting the discrepancies that can come about from
different cancer facilities. The variables considered were age, gender,
histological subtype, time of relapse, stage, B symptoms at relapse, and lab
tests at relapse and were analyzed as individual and as a whole. The

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Cihon
Appl Onc II
4/22/2013

surviving patients were followed for another 20 years which allowed

information collected to also include patients outside the clinical trial.3(p1291)
Out of the 308 patients, 272 (80%) achieved complete remission (CR)
with only a slightly significant difference in age, greater than or at 60 years
old (82%) and less than 60 years was 90%. The relapse rates were similar for
the young and older patients but were found to decrease slightly for patients
with lymphocyte predominant compared to other subtypes.3(p1291) The second
CR for relapse patients decreased significantly for older patients treated
initially with radiation therapy with 43% for older than 60 years and 85% for
younger than 60 years old. When the variables were looked at
simultaneously for relapse, it was due to old age.3(p1292) Older patients had a
sooner latency period of 3 years between completed radiation therapy and
second cancer but had no association of previous radiation fields to second
malignancy as the younger patients did. This suggests that elderly patients
had second malignancies from old age instead of previous radiation
therapy.3(1294) Patients who relapsed and were treated with rescue chemo
compared favorably with those treated initially with chemo with or without
radiation therapy. After 20 years of observation time 60% of the patients
remained in CR.3(1294)
Although the study showed favorable results, it had some limitations.
With such a long study period of 20-30 years, improvements could have been

Amanda
Cihon
Appl Onc II
4/22/2013

made in radiation therapy that were not taken account for in the trial. This
serves as a disadvantage for this study in that it reduces the reliability of the
study because it cannot be considered true for every time the study is done.
The trial showed no relation of mortality to initial radiation therapy
treatment in elderly patients. With only radiation therapy initially there was a
highly sustained CR rate and no cause of a second malignancy. Even with a
second malignancy the prognosis was about the same whether treatment
was initially with or without radiation therapy. The study showed that relapse
rates, outcomes, and predictors were comparable with radiation therapy
alone initially proving it to be an effective treatment approach in older
patients with early stage HL.
In my clinical practice, I normally do not see older patients being
treated for HL since the standard treatment is with ABVD. After researching
the topic though I think more effort should be put into what we can do to
treat the patients with radiation therapy. It is shown that the elderly have
more toxicity with ABVD and other forms of chemo than they do with
radiation therapy and still have a comparable CR rate with radiation alone.
The quality of life post treatment with radiation therapy or chemo or both is
necessary to consider before choosing a treatment approach for early or late
stage elderly Hodgkins lymphoma patients.

Amanda
Cihon
Appl Onc II
4/22/2013

References
1) Boll, B., H. Gorgen, M. Fuchs, A. Pluetschow, H. T. Eich, M. J. Bargetzi, E.
Weidmann, C.
Junghanss, R. Greil, A. Scherpe, O. Schmalz, D. A. Eichenauer, B.
Von Tresckow, A. Rothe, V. Diehl, A. Engert, and P. Borchmann.
"ABVD in Older Patients With Early-Stage Hodgkin Lymphoma
Treated Within the German Hodgkin Study Group HD10 and HD11
Trials." Journal of Clinical Oncology 31.12 (2013): 1522-529. 20
Apr. 2013. Web. 22 Apr. 2014.
2) Ballova, V. "A Prospectively Randomized Trial Carried out by the
German Hodgkin Study
Group(GHSG) for Elderly Patients with Advanced Hodgkin's
Disease Comparing
BEACOPP Baseline and COPP-ABVD (study HD9elderly)." Annals
of Oncology 16.1 (2005): 124-31. PubMed. 16 Jan. 2005. Web. 22 Apr.
2014.
3) Landgren, O. "A Population-based Cohort Study on Early-stage Hodgkin
Lymphoma
Treated with Radiotherapy Alone: With Special Reference to Older
Patients." Annals of Oncology 17.8 (2006): 1290-295. 1 June
2006. Web. 22 Apr.
2014.
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Cihon
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