Annals of Oncology 11: 1615-1616. 2000.
© 2000 Kluwer Academic Publishers Printed in the Netherlands.
Clinical case
Radiation myositis: The possible role of gemcitabine
G. Ganem, P. Solal-Celigny, A. Joffroy, D. Tassy, A. Delpon & O. Dupuis
Radiation Oncology Department, Centre Jean Bernard, Le Mans, France
Key words: chemotherapy, gemcitabine, radiotherapy, radiation myositis
Introduction
In the October 1999 issue of this journal, Welsh et al. [1]
reported an intriguing case of radiation myositis.
In our center, we observed a similar case, in which a
potential role of gemcitabine is suggested.
Case presentation
A 58-year-old woman underwent surgical treatment of
a squamous-cell carcinoma of the inferior lobe of the
right lung in January 1996. The disease stage was T3N2.
The patient received post-operative radiotherapy (RT).
A cumulative dose of 45 Gy ( 5 x 2 Gy per week) was
delivered from 22 March 1996 to 24 April 1996. A boost
of 10 Gy was also delivered to the right hilar region. In
January 1997, the patient developed bone metastases.
The bone scan showed abnormal fixation in the right
pubo-ischiatic and cotyloid region and metastasis was
confirmed by magnetic resonance imaging. Radiother-
apy was delivered to opposed anterior and posterior
fields (Figure la) as a total dose of 33 Gy in 11 fractions
over 15 days. At the end of February 1997, pain had been
well controlled and the patient began a chemotherapeutic
regimen combining gemcitabine (GEM) and cisplatin
(CDDP). On February 17, 1997: GEM was administered
at a dose of 1000 mg/m2 on days 1, 8 and 15 and CDDP
at a dose of 100 mg/m2 on day 15. The patient had
received three courses by April 1997, but the CDDP dose
was reduced because of poor gastrointestinal tolerance.
At the end of May 1997, the patient developed very
painful 'cellulomyositis' of the right buttock. The bone
scan showed atypical fixation in the right gluteal muscles
that coincided with the radiation fields, together with
significant regression of the pathologic bone fixation
(Figure lb). The CT scan of the region was considered
normal. Magnetic resonance imaging showed a diffuse
hypersignal and edema on the T2-weighted images of
gluteal soft tissue, coinciding with the radiation fields
and compatible with the diagnosis of radiation myositis.
Symptomatic treatment, consisting in oral opiates, anti-
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biotics and steroids, was prescribed. The pain was very
difficult to control but was progressively alleviated over
three months. The patient's course was characterized by
progression of the bone metastases and the patient died
in January 1998.
Comments
Radiation-induced muscle injury is infrequently reported
in the literature, as Welsh et al. point out in their article
[1]. A possible determinant of radiation-related muscle
injury is a 'high' dose per fraction [2], but lesions usually
(but very infrequently) occur at a total dose of over
50 Gy.
Although there was no histological confirmation of
subacute radiation induced myositis, the case history
appeared very similar to that reported by Welsh et al. [1].
A potential role of gemcitabine was considered in view
of the similarity in the chronology of the present case
and that previously reported. Moreover, since those two
cases, at least two other reports of radiation recall have
recently been published [3,4].
The time sequence of the clinical case reported herein
is not consistent with a classic radiation recall phenom-
enon, because symptom onset occurred after the third
chemotherapeutic cycle and because radiation therapy
was delivered less than six months previously, while six
months is considered the lag time for subacute radiation
reactions [5]. Phase I—II studies evaluating combined
GEM and radiotherapy showed that GEM dose must be
considerably reduced, in comparison to combination
chemotherapy without radiation therapy, because of
severe side effects, probably related to major potentiation
of the cytotoxic effects of combined GEM and radiation
therapy [6, 7].
The mechanisms by which GEM enhances subacute
reactions to radiation therapy have yet to be elucidated.
Gemcitabine is a pyrimidine analogue like cytosine-
arabinoside. After crossing the cell membrane, GEM is
activated by deoxycytidine kinase, forming mono-, di-
and triphosphate metabolites. A deficit in that enzyme is
1616
CENTRE JEAN BERNARD
LE MANS
STUDY 13
&
(a)
CENTRE JEAN BERNARD
LE MANS
STUDY 12
(b)
Figure I. Bone scan imaging and radiation port.
the principal mode of resistance [8]. X-ray radiation may
induce increased thymide phosphorylase (dThdPase)
levels in some tumors. The later is the essential enzyme
in activation [9] of capecitabine, which is also a nucleo-
side analogue with radiosensitizing properties [10]. Those
observations are consistent with an indirect effect medi-
ated by TNF-a and induced by X-ray irradiation in
tumors and possibly host stromal normal cells. These
processes may take six days and peak nine days post-
irradiation, but have not been studied at later time
points. The mechanism has been identified as one of the
potential radiosensitization factors observed with cape-
citabine. To our knowledge, there is no data on the
influence of X-ray irradiation on intracellular deoxy-
cytidine deaminase levels in tumors, or on those in
normal tissues, and particularly the muscles.
The very intriguing points in these two clinical cases
are: 1) the time sequence; 2) the use of GEM about two
months after radiotherapy; 3) the sites of the radiation
myositis (i.e., the gluteal region) and 4) the favorable
course after about two months.
References
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Ann Oncol 1999; 10: 1105-8.
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Received 10 April 2000; accepted 11 May 2000.
Correspondence to:
G. Ganem, MD
Radiation oncology Department
Centre Jean Bernard
9 Rue Beauverger
72000 Le Mans
France
E-mail: coutard@cybercable.tm.fr