Role of Radiotherapy in Ovarian Cancer - Review Article
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INDIAN JOURNAL OF MEDICAL & PAEDIATRIC ONCOLOGY Vol. 28 No 4, 2007 18
Review Article
Role of Radiotherapy in Ovarian Cancer
T. KATARIA, SHRAVAN KUMAR
SUMMARY radiotherapy (RT) in the management of ovarian
cancer is controversial and not clearly
Carcinoma ovary is diagnosed at a late stage
established.2 Similarly, the potential role of RT
due to paucity of symptoms and non-
in the consolidative treatment and as salvage
availability of any specific screening tools.
therapy following CT failure remains
The available modalities of treatment viz;
controversial. In this review, we have tried to
surgery and /or chemotherapy give only 25-
analyze the existing data on the value of
40% survival in advanced stage disease. No
radiotherapy in the treatment of epithelial
large scale randomized trials are available
ovarian cancer.
to provide a guidance to role or sequence of
radiation therapy in epithelial carcinoma of EARLY STAGE EPITHELIAL OVARIAN CANCER
ovary. The article is a brief attempt to (FIGO STAGE I & II)
sensitize the readers to the non-utilized
application of an effective modality of Clinical trials have evaluated the postoperative
treatment and gain an audience to find ways impact of both radiation therapy and
of applying radiation in the era of targeted chemotherapy upon the survival of patients with
techniques along with conformal avoidance early stage disease 3-5. There have been two
that was not possible in the times of randomized studies of external-beam pelvic
orthovoltage/cobalt therapy. radiation therapy in patients with Stage I
tumours 5,6 A Princess Margaret Hospital
INTRODUCTION randomized trial of 147 patients compared
pelvic radiotherapy alone or with chlorambucil
Ovarian cancer is the fifth most common cancer
chemotherapy to whole abdomen radiotherapy,
among women with a lifetime risk of about 1 in
in patients with stages I-III disease 5. After a 7
70. It is the leading cause of death with highest
year follow-up, the 10-year difference in survival
fatality to case ratio of all the gynecologic
was significantly higher in the 76 patients
malignancies. 70-75% of the cases are diagnosed
treated with pelvis plus whole abdomen
at an advanced stage and early detection is
radiotherapy compared to the 71 patients treated
difficult. Despite advances in the treatment of
with pelvic irradiation and chlorambucil (46%
epithelial ovarian cancer in the past decade, this
vs 31%, p=0.05). The survival benefit was only
disease still poses a great challenge, 5-year
seen in patients with small macroscopic residual
survival of advanced stage ranging from 15-25%.
tumour (INDIAN JOURNAL OF MEDICAL & PAEDIATRIC ONCOLOGY Vol. 28 No 4, 2007 19
for complete surgical staging, makes it difficult radiation in eradicating residual tumours is
to draw conclusions from this study. Both studies dependent on the number of clonogenic cells
failed to demonstrate superiority for any form of present. Thus, the limitations imposed by the
therapy. While pelvic radiation produced a tolerance of the normal tissues in the abdomen,
reduction in the rate of pelvic relapses, distant particularly the gastrointestinal tract, imply
relapses occurred throughout the peritoneal that whole-abdominal irradiation would produce
cavity, leading to the same overall relapse rate. a modest improvement in tumour control in the
upper abdomen, but this benefit would be seen
Abdominal pelvic radiation therapy has only in patients with small numbers of residual
not been the subject of a Phase III trial in clonogenic cells or microscopic disease
patients with Stage I disease but has been residuum in the upper abdomen. There is little
retrospectively compared to pelvic radiation or no curative potential for abdominal
therapy or no treatment.7 No benefit was found irradiation in patients with bulky disease in the
in grade 1 patients, where the risk of relapse was upper abdomen.
under 5% overall. In grades 2 and 3, a
statistically non significant reduction in relapse CHOICE OF RADIATION TECHNIQUE
risk was observed. In patients whose tumours
were densely adherent, a significant reduction Several techniques for delivering radiation to
in relapse was associated with the use of the entire peritoneal cavity have been
abdominal pelvic radiation therapy. These developed. The two most commonly used are the
patients are more correctly classified and moving-strip technique, in which a small part
treated as having Stage II disease. of the abdomen is irradiated daily sequentially;
and the open-field technique, in which the
RADIATION THERAPY whole volume is treated daily. The moving-strip
technique was initiated in an era when
Pivotal to the use of curative radiation in radiation therapy equipment could not
ovarian cancer is recognition that ovarian adequately encompass the large volumes
cancer has a dominant route of dissemination required in one portal.9 It was justified because
throughout the peritoneal cavity and that a biologically higher dose can be delivered
tumour remains confined to the abdominal sequentially to the smaller volumes than could
cavity for extended periods of time. In fact, at be delivered simultaneously to the whole volume
first relapse, regardless of therapy, tumour is in the open-field technique. The duration of the
confined to the abdominal cavity in entire treatment course, however, using the
approximately 85% of patients. 8 Thus, for moving-strip technique was approximately
radiation to be of curative benefit, techniques twice that of the open field. Theoretically, the
that encompass the whole peritoneal cavity, prolonged treatment course might allow
rather than just the pelvis or lower abdomen accelerated proliferation of tumour 10 and
alone, are likely to be most beneficial. Several possible reseeding of tumour metastases from
studies have compared treatment using the untreated area of the peritoneum back to the
abdomino-pelvic radiation therapy with pelvic previously treated area. Given the movement of
radiation therapy alone or combined with the abdominal contents from day to day, there is
single-agent alkylating chemotherapy. 5 These also some uncertainty about the dose received
studies demonstrate a superior outcome using by mobile organs. These two techniques have
abdomino-pelvic radiation therapy for patients been compared with the commonly used
with minimal residual disease after primary radiation doses and fractionation schemes.9 In
surgery. both studies the difference in 5-year survival
between the two treatment approaches was less
The dose of radiation that can be delivered
than 1%. The analysis of the Princess Margaret
safely to the upper abdomen is considerably
Hospital study shows the two techniques to be
lower than that which would be considered
comparable in all patient subgroups, regardless
optimal and sufficient for the successful
of sta ge, histolo g y, g rade, or tumour
treatment of solid tumours. The efficacy of
residuum. 11,12 Further more, there were noINDIAN JOURNAL OF MEDICAL & PAEDIATRIC ONCOLOGY Vol. 28 No 4, 2007 20
differences in acute toxicity between the two SELECTING PATIENTS FOR ABDOMINO-
treatment techniques. Although late PELVIC RADIATION THERAPY
complications were infrequent with either
method, they were less commonly encountered Abdomino-pelvic radiation therapy has been
with the open-field technique. The open-field used during the past 15 years in all stages and
technique has become the standard in most extents of ovarian cancer. 14 From these
centers because of shorter duration of randomized and nonrandomized studies,
treatment, technical simplicity, and reduced considerable data have defined the patient and
toxicity. Variations in the open-field technique tumour factors that will predict a favorable
including adding T-shaped boost portal to the outcome after the use of abdomino-pelvic
para-aortic nodes and medial domes of the radiation therapy. Besides the general medical
diaphragm and treating the upper and lower condition of the patients and their suitability for
abdomen through separate portals. such therapy, the tumour factors that determine
While the technique of radiation is likely suitability include the extent of disease at
to continue to be that of the open field, recent presentation, the amounts and sites of residual
radiobiological information suggests theoretical disease in the pelvis and abdomen, and the
strategies to change radiation fractionation histopathological findings (grade and type) of
schemes to increase the biologically effective the tumour.
dose delivered without increasing radiation
toxicity. The effect of a simple dose escalation A multivariate analysis of pathological
using the same 1 Gy dose per fraction of prognostic factors was performed for an initial
abdominal irradiation was examined in a cohort of patients treated between 1971 and
randomized trial by Morgan et al.13 Escalation to 1978. 15 A second cohort of patients treated
a total abdominal dose of 27.5 Gy in 27 fractions between 1979 and 1985 was examined to test the
validity and reproducibility of the original
did not result in improved disease or overall
prognostic classification. The derived prognostic
survival nor was toxicity increased. Possible
classification has been used to select treatment
changes in radiation fractionation schemes
by classifying patients with ovarian cancer into
include delivering two to three fractions per day
low, intermediate, or high-risk categories. The
of fraction size less than 1 Gy. Using such a low-risk group is composed of patients with
scheme, with an open-field technique, it was Stage I ovarian cancer, who by multifactorial
possible to deliver 30.6 Gy in 0.8 Gy fractions analysis of prognosis within Stage I have been
twice daily with a pelvic boost of 1,519.2 Gy determined to have such a good survival (96%
to the pelvis; treatment was well tolerated and ± 2%) that no postoperative therapy is
did not appear to result in any increased late warranted. These patients at low risk for
toxicity. Authors used this technique to treat 15 recurrence after surgery alone are those with
patients with known residual disease after Stage I, grade 1 disease, without evidence of
induction with cis-platin based regimens. dense adherence or ascites. The remainder of
Limiting the kidney and liver doses to 20 Gy patients with Stage I disease, i.e., those with
and 30.4 Gy respectively ,all patients completed grade 2 or 3, or with dense adherence or ascites,
the planned treatment and only two patients have a significant risk of relapse and fall into the
required a treatment break for thrombo- inter mediate-risk g roup. Cur rently, the
cytopenia. No episodes of small bowel randomized studies in the management of Stage
obstruction were reported in the study. Changed I disease have failed to show a significant
fractionation schemes, with or without advantage for treatment.While a curative
accompanying “chemotherapy,” war rant benefit for abdomino-pelvic radiation therapy
exploration to determine whether they will be has not been established in Stage I disease,
of increased curative benefit in patients with except for those with dense adherence, it has
optimal disease or whether they will even be been established as curative therapy for a large
useful treatment for some patients with proportion of patients with Stage II disease
suboptimal disease. whose residuum is less than 2 cm. 16 Thus, itINDIAN JOURNAL OF MEDICAL & PAEDIATRIC ONCOLOGY Vol. 28 No 4, 2007 21
seems appropriate at this time to consider that chemotherapy or radiation therapy should
abdomino-pelvic radiation therapy or platinum- stimulate an interest in the use of radiation
based chemotherapy are both rational options therapy in ovarian cancer. While many
for management of the high-risk patient with investigators were quick to discard radiation
Stage I disease i.e., those with grade 2 or 3 therapy from the ar mamentarium for
tumours, with large-volume ascites, and/or management of ovarian cancer when cisplatin
positive peritoneal cytologic finding, and those was believed to be a promising agent for
with dense adherence. improved cure rates, it is now apparent that
decision may have been ill-conceived. It would
In selecting patients with Stages II and III now appear to be appropriate to further
disease for whom abdomino-pelvic radiation investigate the role of radiation therapy, either
therapy is appropriate, the amount and site of as a sole agent or as part of a multimodality
residual disease and the tumour grade are strong treatment in the primary management of
determinants of success of outcome. Given the ovarian cancer. With the demonstration that
restrictions on the dose deliverable to the upper paclitaxel is a highly active cytotoxic agent in
abdomen and pelvis, abdomino-pelvic ovarian cancer and that interaction may occur
irradiation should be used only in patients with between this agent and radiation it would seem
no macroscopic disease in the upper abdomen appropriate to explore their concurrent use in
and with small macroscopic (0 to 2 cm) residual ovarian cancer.20 Kong and colleagues treated
disease in the pelvis. This classification of patients with sequential chemotherapy, second-
patients into risk groups has been validated by look surgery, and whole-abdominal radiation
three other investigators in New Germany 16 therapy.21 In that study, a total dose of 30 Gy was
Haven17 and in Denmark.18 The patients in the delivered to the abdomen in 1 Gy fractions twice
intermediate-risk category constitute about 33% daily, and only one patient developed bowel
of the total patient population with ovarian obstruction. To date, no studies have been
cancer. It is in this intermediate-risk group that reported examining either the toxicity or
abdomino-pelvic radiation therapy is the most efficacy of salvage or consolidation whole
appropriate as the sole postoperative treatment abdomino-pelvic irradiation after paclitaxel-
method. These patients are mainly derived from based chemotherapy.
patients with Stages I and II disease, including
PALLIATION
those with dense adherence. Those with Stage III
disease are suitable for this treatment alone if Recurrent or persistent ovarian cancer after
their macroscopic residual tumour is less than first-line chemotherapy is incurable. Patients
2 cm, is located in the pelvis, and is grade 1. are often symptomatic, with generalized or
Using abdomino-pelvic radiation therapy, more localized abdominal symptoms from intra
than 67% of intermediate-risk patients were peritoneal disease. Usually, second, third, or
alive and disease-free 10 years after treatment, fourth-line chemotherapy is used in attempts to
with minimal late morbidity. Recognition of this prolong life and palliate symptoms. Reported
poor outcome led to examine, in a response rates range between 10% and 43% and
nonrandomized study, the use of six cycles of are associated with various toxicities. 2 2
cisplatin-based combination chemotherapy, Radiation therapy as a palliative modality in
followed by abdominopelvic radiation therapy. ovarian cancer is often neglected but may be
In these high-risk, optimally cytoreduced very useful if the sole or dominant symptomatic
patients, the sequential therapy appeared to problem for the patient is localized to a site and
improve their median survival time and relapse- volume that may be safely encompassed in a
free rate significantly, compared to that achieved radiation field. For example, a fixed pelvic mass
by radiation therapy alone.19 eroding the vaginal mucosa causing bleeding,
pain, or bowel or bladder dysfunction may occur
Sequential Chemotherapy and Radiotherapy
without obvious disseminated symptomatic
The similarity of the long-term survivals for peritoneal disease. Tumour regression or
patients treated with platinum-containing symptomatic relief can often be obtained inINDIAN JOURNAL OF MEDICAL & PAEDIATRIC ONCOLOGY Vol. 28 No 4, 2007 22
these situations from local irradiation. Similarly 9. Dembo AJ, Bush RS, Beale FA, et al. A randomized
clinical trial of moving strip versus open field whole
radiation may be employed to treat localized abdominal irradiation in patients with invasive
masses elsewhere in the abdomen, such as the epithelial cancer of ovary. Int J Radiat Oncol Biol
retroperitoneal nodes. Patients with isolated Phys 1983;9:97-102.
brain metastasis should be treated with surgical 10. Withers HR, Taylor JMG, Maciejewski B. the hazard
resection followed by whole brain irradiation of accelerated tumour clonogen repopulation during
radiotherapy. Acta Oncol 1988;27:131-46.
and chemotherapy when possible. Patients may
survive up to 3 years with this combination 11. Dembo AJ, Bush RS, Beale FA, Bean HA, Pringle JF,
Sturgeon JF. The Princess Margaret Hospital study
treatment.23 of ovarian cancer: stage I, II and asymptomatic III
presentations. Cancer Treat Rep 1979;63:249-54.
CONCLUSION
12. Dietl J, Marzusch K. Ovarian surface epithelium and
There is paucity of data on definitive role of human ovarian cancer. Gynecol Obstet Invest
radiation for management of carcinoma ovary 1993;35:129-35.
till date. The advent of organ sparing 13. Morg an L, Chafe W, Mendenhall W, Marcus R.
radiotherapy techniques in the last decade along Hyperfractionation of whole-abdomen radiation
therapy: salvage treatment of persistent ovarian
with a better understanding of ovarian cancer’s carcinoma following chemotherapy. Gynecol Oncol
natural history can be translated into 1988;31:122-36.
prospective trials with/without chemotherapy. 14. Delclos L, Smith JP. Ovarian cancer, with special
These trials may be able to harvest the benefits re g ard to types of radiother apy. NCI Mono g r
for carcinoma ovary over and above achieved 1975;42:129.
by improved surgical techniques and the 15. Dembo AJ, Bush RS, Brown TC. Clnicopathological
correlates in ovarian cancer. Bull Cancer (Paris)
available chemotherapy agents. 1982;69:292-97.
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