Clinical Oncology 23 (2011) 476e481

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Clinical Oncology
journal homepage: www.elsevier.com/locate/clon

Original Article
A Hypofractionated Radiotherapy Regimen (0-7-21) for Advanced
Gynaecological Cancer Patientsq
Jing Yan *, M. Milosevic *y, A. Fyles *y, L. Manchul *y, V. Kelly *y, W. Levin *y
* Radiation Medicine Program, Princess Margaret Hospital, Toronto, ON, Canada
y
Department of Radiation Oncology, University of Toronto, ON, Canada

Received 28 June 2010; received in revised form 10 November 2010; accepted 5 January 2011

Abstract
Aims: To evaluate the efficacy of a palliative three fraction radiation regimen delivered on days 0, 7 and 21 (0-7-21 regimen) for advanced stage gynaecological
cancer patients.
Materials and methods: Fifty-one patients with advanced gynaecological cancer who were treated with the 0-7-21 regimen between 1998 and 2008 were
identified. The median follow-up period was 1.4 months (range 0.2e33.4). Treatment completion data, symptomatic response, toxicity and survival were
retrospectively analysed.
Results: Forty-eight patients received at least two of the three planned fractions. Complete and partial responses of vaginal bleeding were seen in 92% of
26 evaluable patients. Complete and partial responses of pain were seen in 76% of 25 evaluable patients. Eighteen of the 33 evaluable patients experienced grade
1/2 acute toxicity. No patients experienced grade 3/4 toxicity. Grade 1/2 and grade 3 late toxicity occurred in four and one of 12 evaluable patients, respectively.
Grade 5 toxicity was assigned in two patients. It was uncertain whether these deaths were radiation related or due to tumour progression. Eleven patients
survived longer than 12 months.
Conclusions: The 0-7-21 regimen provided effective and rapid symptomatic relief with acceptable toxicity, and offered the advantage of convenience for most
patients. It offers an alternate treatment option for carefully selected patients with incurable gynaecological malignancies.
Ó 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Key words: 0-7-21 radiotherapy; advanced gynaecological cancer; hypofractionation; palliation

Introduction Various hypofractionated radiation therapy regimens have

Radiation therapy is an effective treatment modality for
the palliation of pelvic symptoms due to gynaecological
malignancies [1,2]. Appropriate treatment prescriptions
need to consider the potential toxicities, the patients’
anticipated life expectancies, their mobility and ability to
attend the treatment facility [2]. Short course treatment
regimens can significantly reduce the physical inconve-
nience and the time commitment for the patient and
caregivers [3]. In addition, it might be more acceptable, for
those patients with impaired mobility or who need to travel
long distances or have psychosocial challenges [4].
q Presented at the 27th European Society for Therapeutic Radiology and
Oncology Annual Scientific Meeting, Goteborg, Sweden, 11e14 September 2008.
Author for correspondence: W. Levin, Room 5-959, Department of Radia-
tion Oncology, Princess Margaret Hospital, 620 University Avenue, M5G 2M9,
Toronto, ON, Canada. Tel: þ1-416-946-2127; Fax: þ1-416-946-4442.
E-mail address: Wilfred.Levin@rmp.uhn.on.ca (W. Levin).
been described that provide palliation for patients with
locally advanced pelvic malignancies and poor performance
status [5,6]. Boulware et al. [7] described the use of 10 Gy
fractions to the whole pelvis (once per month to a maximum
total dose of 30 Gy) for advanced gynaecological cancers. This
regimen was well tolerated and achieved adequate palliative
responses [4,8e10]. The addition of concomitant misonida-
zole to 10 Gy fractions as described in a Radiation Therapy
Oncology Group (RTOG) phase II trial resulted in unaccept-
ably high toxicities to patients with advanced pelvic malig-
nancies [11].
A radiation therapy prescription that delivered a total
tumour dose of 24 Gy in three equal fractions with intervals
of 7 days between fractions 1 and 2, and 14 days between
fractions 2 and 3 (0-7-21 regimen) has been successfully
used in a small group of locally advanced prostate cancer
patients with haematuria [12]. 750 cGy  five weekly doses
administered to the whole pelvis in patients with advanced

0936-6555/$36.00 Ó 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.clon.2011.01.001
 J. Yan et al. / Clinical Oncology 23 (2011) 476e481 477

gynaecological tumours was reported in a randomised trial for Adverse Events v3.0 (CTCAE) and classified as early or
[13]. Other regimens include 17 Gy in two fractions over 3 late according to the time of onset. The maximum toxicity
days, 21 Gy in three fractions given on alternate days or scores were assigned. Descriptive statistics were used to
30e36 Gy in five to six fractions given once or twice per summarise the treatment outcome and toxicities.
week for patients with advanced bladder cancer [14e19].
The 0-7-21 regimen is a radiation therapy option
commonly used for diverse palliative clinical scenarios at Results
our institution. This study serves to report our experiences
with this regimen in women with advanced gynaecological Patient and disease characteristics for the 51 patients are
cancers with respect to patient selection and treatment summarised in Table 1. The main symptoms requiring
compliance, symptom control, radiation-induced morbidity palliation were vaginal bleeding and pelvic pain.
and survival. The radiation therapy details are summarised in Table 2.
Treatment field arrangements, radiation therapy modality
and tumour dose were selected at the discretion of the
Materials and Methods treating physician. Thirty-three patients were treated with
anterior and posterior parallel opposing fields using 6 or
After local research ethics board approval, a retrospective 18 MV photons. The high dose volume typically included
chart review was conducted at our institution for all the primary tumour alone.
advanced stage gynaecological cancer patients, between
1998 and 2008, who received palliative radiation therapy. In
total, 55 patients who were prescribed the 0-7-21 regimen Table 1
were identified from our departmental records. Four Patient characteristics (n ¼ 51)
patients were excluded from the analysis because their
Characteristics Number
medical charts were not available. All patients were
Age (years)
considered to have incurable cancer with a life expectancy
Median 72.5
less than 1 year using available therapies, as well as they
Range 32e93
were deemed unlikely to comply with the requirements of
Tumour site (n)
radical treatment by virtue of major co-morbidities.
Uterus 18
After the initial consultation with the radiation oncologist,
Cervix 13
the patients gave informed consent for palliative treatment. Ovary 4
The intention was to give a maximum of three fractions if Vagina 6
needed to maximise the palliation effect. All patients were Vulva 10
assessed before each treatment fraction to determine Overall stage (n)
whether they should proceed with the subsequent treat- Stage III 4
ments. Reasons for discontinuation were achievement of Stage IVA 9
symptom palliation, deterioration of performance status, Stage IVB 14
worsening symptoms, severe radiotherapy-related toxicity or Recurrence 11
tumour progression. Treatment was continued in patients Recurrence and distant metastasis 10
with persistent symptoms and mild toxicity. In patients with Unknown 3
significant tumour response, the treatment fields were Histology (n)
modified to treat smaller volumes to minimise the risks of Squamous cell carcinoma 24
normal tissue toxicity. Adenocarcinoma 19
Carcinosarcoma 2
On completion of the radiation therapy the patients were
Sarcoma 1
offered a 4 week follow-up appointment. Routine follow-up
Melanoma 3
radiological imaging was not scheduled. Follow-up care was Unknown 1
conducted by community care nurses, palliative care teams
Primary symptoms requiring palliation
or family physicians.
Vaginal bleeding 21
Data were abstracted from the physician notes in the Pelvic pain 14
hospital clinical records. Four categories of response were Vaginal bleeding and pelvic pain 11
assigned according to clinical description, namely complete Other 5
response, partial response, no change and deteriorating Co-morbidities
symptoms as they applied to the index symptoms of vaginal Medical* 17
bleeding or pelvic pain. Acute toxicity was defined as Mobilityy 11
toxicity that occurred within 90 days of completing radia- Psychiatricz 9
tion treatment. Only patients who survived 90 days or more Drug addiction 3
were analysed for late effects. Treatment-related side- * Diabetes mellitus, hypertension, cardiovascular disease.
effects were recorded by the treating oncologist in clinical y
Arthritis, osteoporosis, hemiplegia or poor performance status.
notes. The toxicities were retrospectively graded by a single z
Schizophrenia, dementia, depression and organic brain
observer (JY) based on the Common Terminology Criteria syndrome.
478 J. Yan et al. / Clinical Oncology 23 (2011) 476e481

Table 2 Table 4
Radiation treatment details Acute and late radiation-induced toxicities

Dose fraction size No. (%) Acute side-effects Late side-effects

600 cGy 2 (3.9%) (n ¼ 33) (n ¼ 12)
700 cGy 44 (86.2%)
None 14 6
800 cGy 5 (9.8%)
Gastrointestinal
Number of fractions
Grade 1/2 10 1
One 3 (5.9%)
Grade 3/4 e e
Two 19 (37.3%)
Grade 5 1 1
Three 29 (56.9%)
Genitourinary
Radiation technique
Grade 1/2 1 2
AP/PA POP 33 (64.7%)
Grade 3/4 e e
Four-field box 10 (19.6%)
Grade 5 e e
Three field 4 (7.8%)
Skin
Direct apposition 2 (3.9%)
Grade 1/2 7 e
Other 2 (3.9%)
Grade 3/4 e e
Radiation modality
Grade 5 e e
6/18 MV EBRT 49 (96.1%)
Bone
Electrons 2 (3.9%)
Grade 1/2 e 1
AP/PA POP, anterior posterior parallel opposed pair; EBRT, external Grade 3/4 e 1
beam radiotherapy. Grade 5 e e

All patients were clinically assessed before each treat-

septic shock. This event was assigned as a grade 5. Fourteen
ment fraction. Among the 51 patients, radiation therapy
patients had no acute toxicities.
was discontinued after one fraction in three patients
There were only 12 patients with adequate documenta-
because of deterioration in performance status and frailty.
tion regarding late complications. Grade 1/2 gastrointes-
Forty-eight patients had at least two fractions (29 patients
tinal, genitourinary or bone toxicities were reported in four
received all three fractions). The third planned fraction was
patients. Grade 3 bone toxicity, sacral insufficiency fracture,
discontinued in 19 patients (37%) because adequate pallia-
occurred in one patient. One patient died after surgery of
tion had been achieved in seven patients, significant acute
bowel obstruction of undetermined causes. This was also
toxicities occurred in four patients, performance status
assigned as grade 5.
deteriorated in four patients, no response in one patient and
In preparation of this analysis, the patients’ family
reasons were not stated for three patients.
physicians were contacted to update patient status where
Symptomatic responses were assessed during the course
they were lost to follow-up. Eighteen patients were
of treatment and are summarised in Table 3. Information on
confirmed dead at a median time of 7.4 months (range
vaginal bleeding was available in 26 patients. Ninety-two
0.6e99 months) from the radiation therapy start date.
per cent (24/26) of patients had significant improvement.
Other than the deaths of two patients that could not be
Information on pain was available in 25 patients. Changes in
reliably ascribed to disease progression or radiation therapy
pain were assessed as complete, partial or no response
complication, all the deaths were due to progressive cancer
in 20, 56 and 12%, respectively. Pain symptoms worsened in
or co-morbid medical conditions. Eleven patients survived
12% (3/25).
more than 12 months, median survival 20.2 months (range
The length of follow-up was measured from the date of
12.9e99). All patients had clinically detectable persistent
the last radiation therapy fraction. The median follow-up
disease except one who had a significant partial regression,
for all patients was 1.4 months (range 0.2e33.4). The side-
as demonstrated on magnetic resonance imaging 12
effects are summarised in Table 4. The acute toxicity data
months after radiation treatment.
were available for 33 patients. Grade 1/2 toxicities included
diarrhoea, proctitis, abdominal pain, nausea, urinary
frequency and perineal skin reactions and were reported in Discussion
18 patients. One patient developed large bowel obstruction
2 months after radiation. She died after surgery due to
This retrospective study examined our 10-year institu-
tional experience involving 51 patients with incurable
gynaecological cancers in which we used the 0-7-21 radiation
Table 3
therapy regimen. The 0-7-21 regimen was the maximum
Symptom control
intended prescription. The indication for treatment was
Symptom relief Bleeding (n ¼ 26) Pain (n ¼ 25) palliation of symptoms and if this was achieved after two
Complete response 16 (61.5%) 5 (20%) fractions the treatment was discontinued to minimise the
Partial response 8 (30.8%) 14 (56%) risks of late toxicity and to retain normal tissue tolerance so
No change 2 (7.7%) 3 (12%) that additional radiation therapy could be given later if
Deteriorating symptoms 0 (0%) 3 (12%)
needed.
Table 5
Literature review: Hypofractionated RT prescriptions for palliation of pelvic malignancies

Reference Site No. patients Dose (Gy) Fraction size Symptom control (bleeding)
[7] Gynaecological 86 30 10 Gy/fraction, 1 fraction: 39/86 (45%) complete or partial response
every 3e4 weeks 2 fractions: 47/55 (85%) complete or partial response
3 fractions: 20/20 (100%) complete or partial response
[9] Gynaecological 30 30 10 Gy/fraction, every month 30/30 (100%) alleviation of symptoms
[8] Gynaecological 27 30 10 Gy/fraction, every month 22/22 (100%) complete response
[10] Gynaecological 42 30 10 Gy/fraction, every month 18/30 (60%) complete response

J. Yan et al. / Clinical Oncology 23 (2011) 476e481

9/30 (30%) partial response
3/30 (10%) no response
[11] Gynaecological, colorectal, 142 30 10 Gy/fraction, every month 3 fractions: 41% complete or partial response
genitourinary
[4] Gynaecological 64 30 10 Gy/fraction, every month 53/59 (90%) complete or partial response
[22] All types of pelvic cancer 144 44.4 3.7 Gy, twice a day  2, repeat 10% complete response, 22% partial response;
every month 24% no change
[23] All types of pelvic cancer 136 44.4 3.7 Gy, twice a day  2, 97% (71/73) complete or partial response
repeat every
month or every 2 weeks
[18] Bladder 41 17 versus 45 8.5 Gy, every other day  2 17 Gy: 59% clearance of haematuria
versus 3.75 Gy,12 fractions, 45 Gy: 16% clearance of haematuria
over 26 days
[16] Bladder 65 30 or 36 6 Gy every week  5 or 6 92% complete response of haematuria
[15] Bladder 65 30 6 Gy every week  5 62% (23/37) complete response
[19] Bladder 162 21 7 Gy, every other day  3 27/52 (52%) complete or partial response
[12] Prostate 13 24 8 Gy, 0-7-21 1 fraction: 11/13 complete response
[14] Bladder 272 35 versus 21 3.5 Gy, every day  10 versus Symptomatic improvement at end of treatment
(53% versus 50%)
7 Gy, every other day  3 Symptomatic improvement at 3 months
(71% versus 64%)
Present study Gynaecological 51 18, 21 or 24 6e8 Gy, 0-7-21 16/26 (62%) complete response; 8/26 (31%)
partial response

479
480 J. Yan et al. / Clinical Oncology 23 (2011) 476e481
Various published hypofractionated palliative regimens
for the pelvis are presented in Table 5. We observed
complete or partial relief of vaginal bleeding in 92% of the
26 assessable patients in this study. Our results are
comparable with others who used a 10 Gy single fraction of
pelvic radiation therapy in gynaecological cancer patients
[4,7,10]. They reported symptomatic relief of vaginal
bleeding in 85e100% of patients when treated with two or
three 10 Gy fractions. We observed a reduction in pain, but
it was difficult to interpret because of the concomitant use
of analgesics. Detailed information on analgesic usage was
not collected in this study.
The risks of developing both acute and late treatment-
related toxicities are of concern when using high dose per
fraction radiation therapy. The risks of manifesting long-term
toxicity increase with prolonged survival. Some authors have
recommended that only patients with life expectancies of less
than 9 months or a year should be treated with the 10 Gy
single-fraction protocols [4,10]. Between 18 and 24 Gy in
three fractions is equivalent to 24e36 Gy10 when an a/b ratio
of 10 Gy for early effects is used; EQD2 is 36e48 Gy3 when an
a/b ratio of 3 Gy for late effects is used [20]. The EQD2 for acute
effects is relatively low. Our prescription does not exceed the
late normal tissue constraints of 50 to 70e80 Gy EQD2 as
reported in many publications [21]. The deaths of two
patients could not be confidently attributed to either radia-
tion toxicity or disease progression. From our results, the
acute toxicity rate was acceptable. The late toxicity data must
be interpreted with caution due to the inadequate follow-up
information inherent in a retrospective analysis of palliative
treatments. On the basis of the theoretical EQD2 calculation, it
might be possible to offer additional radiation therapy to
patients who have a recurrence of the original symptoms or
progression of locoregional disease.
Eleven patients (21.6%) survived longer than 1 year. This
was similar to the findings of Onsrud et al. [4] where 28% of
their patients with advanced gynaecological cancers who
received 10 Gy single-fraction irradiation lived longer than
1 year. This reflects the challenge of reliably predicting the
life expectancy of patients when choosing non-curative
radiation therapy prescriptions. ‘Treatment decision-
making’ to determine which patients are candidates for
hypofraction radiation therapy should be on the basis of an
integrated clinical judgment [2,4,10]. For the 11 long
survivors, symptom palliation was maintained during the
follow-up period in 6 patients, whereas one patient
relapsed 33.2 months after treatment. Of these 11 patients,
three were known to have received systemic therapy, either
chemotherapy or hormonal therapy.
Most patients were treated with simple, wide two-field
techniques without normal tissue shielding. In the latter
part of the study period, conformal techniques were applied
for patients to provide normal tissue sparing. We were not
able to discern whether the use of conformal fields affected
toxicity, but advances in both conformal planning and
image-guided radiation therapy delivery certainly warrant
study in the palliative radiotherapy setting.
When considering palliative radiotherapy prescriptions,
the risks of complications must be balanced against the
anticipated benefit, as well as patient comfort and conve-
nience. In the phase II and III RTOG 8502 trial [22,23], efforts
were made to reduce late toxicity by modifying a single large
fraction (10 Gy) to a twice daily fractionation scheme (3.7 Gy
twice a day  four fractions for each cycle). This cycle was
repeated at varying intervals to a total dose of 44.4 Gy in 12
fractions. It was concluded that the incidence of serious late
complications was substantially reduced, but it required
a significant time commitment from the patients and
frequently required hospital inpatient admissions for out of
town patients. Conversely, a prospective, randomised trial
was carried out to explore reducing the number of patient
visits for radiation therapy in locally advanced, inoperable
bladder cancer. It compared regimens of either 35 Gy in 10
fractions versus 21 Gy in three fractions delivered on alter-
nate days [14]. The palliative effect, overall survival rates and
incidence of toxicities were similar for the two groups.
The 0-7-21 regimen seems to be comparable with these
fractionation schemes in terms of palliative effect and late
morbidity (Table 5). From our perspective, the advantages
of the 0-7-21 regimen are that although there may be no
substantive differences in efficacy from other regimens, the
short intervals between fractions allow these patients to be
reassessed for cancer progression and treatable side-effects.
The maximum side-effects occur in the 2 weeks after frac-
tion 2. Reassessment on day 21 gives flexibility to continue
treatment or not. After fraction 3 the treatment is complete.
The timing facilitates patient independence to remain at
home, time for recovery between fractions and the ability to
keep close contact with the treatment facility.
To our knowledge, this is the only study to document the
0-7-21 regimen for patients with advanced gynaecological
cancer. We acknowledge the limitations of this study due to
its small sample size and retrospective data collection.
Moreover, most patients were referred to palliative care
teams, community care or family physicians after completing
the palliative radiotherapy. This resulted in a limited number
of patients who had ‘adequate’ follow-up, which prevented
a comprehensive assessment of the late toxicities and
symptom response rates. However, this analysis does include
all eligible patients treated using this regimen over a 10-year
period at our institution.
Conclusions
In patients with advanced stage gynaecological cancer
who have limited life expectancy and who are judged
unsuitable for radical treatment due to poor performance
status or other physical or psycho-social circumstances, the
0-7-21 regimen provides effective palliation of symptoms,
especially bleeding, with high acceptability by patients for
its convenience and their ability to live at home.
Acknowledgement
The authors acknowledge the contributions of the
Radiation Therapist Writing Group at the Princess Margaret
Hospital.
 J. Yan et al. / Clinical Oncology 23 (2011) 476e481
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