Appropriate Use of Radiation Therapy
ADRENAL METASTASES
Palliative radiotherapy for symptomatic adrenal metastases.
Soffen EM, Solin LJ, Rubenstein JH, Hanks
GE, Cancer 1990 Mar 15;65(6):1318-1320
Ten of 16 patients were treated with 3000 cGy to opposed anterior and posterior fields
(300-cGy fractions [four patients] and 250-cGy fractions [six patients]). The remaining
six patients were treated with a variety of techniques, with total doses ranging from 2925
cGy to 4500 cGy. The patients were analyzed for response at their first follow-up visit (2
to 4 weeks after treatment). The overall response rate was 75% (12 of 16 patients).
Six patients (38%) had complete pain relief without medication that lasted until death.
Two patients had marked pain relief, but still required analgesics. Four patients had
marked or moderate pain relief that did not continue through follow-up. Four patients had
minimal to no response. All patients were observed until death, with a median survival
time after irradiation of 3 months (range, 0.5 to 11 months).
Radiation therapy for adrenal metastases
Soejima T, Hirota S, Hishikawa Y, Hamanaka A, Ozawa Z, Endo M, Kojima Y, Kozuma K, Suzuki
Y, Obayashi K, Takada Y Nippon
Igaku Hoshasen Gakkai Zasshi 1997 Oct;57(12):801-804
Fourteen patients, 13 with primary lung carcinoma and one with primary unknown
carcinoma, received radiation therapy for adrenal metastases from 1984 to 1995. Total
dose ranged from 16 Gy to 60 Gy, and fractional dose from 1.6 Gy/ Fr to 3 Gy/Fr. RESULTS:
Partial response of the local tumor was recognized in 2 of 7 patients by CT imaging. Pain
relief was obtained in 7 of 8 patients. Median survival was 3 months, and 6-month survival
was 28.6% in all patients. CONCLUSION: Radiation therapy is useful for the purpose
of pain relief in adrenal metastases.
BONE METASTASES
The palliation of symptomatic osseous metastases: final results of the
Study by the Radiation Therapy Oncology Group.
Tong D, Gillick L, Hendrickson FR Cancer
1982 Sep 1;50(5):893-899
Ninety percent of patients experienced some relief of pain and 54% achieved
eventual complete pain relief. Important prognosticators included the initial pain
score and the site of the primary lesions. Administration of steroid or chemotherapy
during the one-month on-study period did not influence the frequency of pain relief. The
low-dose, short-course schedules were as effective as the high-dose protracted programs.
Reanalysis of the RTOG study of the palliation of symptomatic osseous
metastasis.
Blitzer PH Cancer 1985 Apr 1;55(7):1468-1472
This is a reanalysis of the data from the Radiation Therapy Oncology Group (RTOG) study of
the palliation of metastasis to bone. The RTOG multicenter clinical trial studied pain
relief in 759 patients randomly assigned to a variety of dose-fractionation schedules: 270
cGy X 15 fractions, 300 X 10, 300 X 5,400 X 5, and 500 X 5. The multivariate
statistical technique of logistic regression was used. The results differed from a
previous report in that number of fractions was statistically significantly related to
complete combined relief (that is, absence of pain and cessation of the use of
narcotics). The conclusion is that protracted dose-fractionation schedules are
more effective than short course schedules.
Single-dose half-body irradiation for palliation of multiple bone
metastases from solid tumors. Final Radiation Therapy Oncology Group report.
Salazar OM, Rubin P, Hendrickson FR, Komaki R, Poulter C, Newall J, Asbell SO, Mohiuddin
M, Van Ess J
Cancer 1986 Jul 1;58(1):29-36
This is the final analysis of Protocol #78-10 which explored increasing single-doses of
half-body irradiation (HBI) in patients with multiple (symptomatic) osseous metastases. When
given as palliation, HBI was found to relieve pain in 73% of the patients. In 20% of the
patients the pain relief was complete; over two thirds of all patients achieved better
than 50% pain relief. The HBI pain relief was dramatic with nearly 50% of all responding
patients doing so within 48 hours and 80% within one week from HBI treatment.
Furthermore, the pain relief was long-lasting and continued without need of retreatment
for at least 50% of the remaining patient's life. These results compare favorably with
those obtained by the Radiation Therapy Oncology Group (RTOG) using several conventional
daily fractionated schemes on similar patients in a prior study (RTOG #74-02). HBI
achieves pain relief sooner and with less evidence of pain recurrence in the irradiated
area than conventionally treated patients. The most effective and safest of the HBI
doses tested were 600 rad for the upper HBI and 800 rad for the lower or mid-HBI. There
were excellent responses found in practically all tumors treated, but especially breast
and prostate among which over 80% of all patients experienced pain relief, 30% in a
complete fashion. Single-dose HBI emerges as one of the safest, fastest, and more
effective palliative tools for intractable cancer pain in modern radiation oncology.
Fractionated half-body irradiation for pain palliation in widely
metastatic cancers: comparison with single dose.
Salazar OM, DaMotta NW, Bridgman SM, Cardiges NM, Slawson RG, Int J Radiat Oncol Biol
Phys 1996 Aug 1;36(1):49-60
PURPOSE: To explore fractionated half-body irradiation (HBI) for pain palliation and
determine if it is more efficient and effective than single dose The HBI fields were 28%
upper, 25% mid, and 47% lower; three patients had both upper and lower HBI. An initial
performance status (PS) 3&4 with a life expectancy < 3 months was found in 50% of
patients. The HBI techniques used on consecutive patients were: single dose (SD) in 54%
with escalating doses of 4-10 Gy; split-course (SC) in 12% with two 4 Gy single doses
separated by 2 weeks; and daily fractionated (DF) in 34% with five fractions of 3 Gy each.
There were 68 of 75 HBI (91%) given for pain control purposes. RESULTS: The percent
total (complete) pain relief was SD-73(32), SC-50(13), and DF-96(49). Time to maximum and
(complete) relief was: SD 5 days each and DF HBI 7(11) days. Pain-free survival (PFS) was
short but so was overall survival (OS). PFS was SD-5, SC-4.5, and DF-19 weeks. The percent
of the remaining patient's life spent pain free without retreatment (NPR) was SD-38,
SC-34, and DF-68. Differences in pain relief, PFS, OS, and NPR were significant
and carried over primary tumor types; prostate, breast, and surprisingly GI were very
responsive (90, 84, and 83%, respectively). Despite lack of premedication in DF-HBI,
toxic reactions were identical to SD-HBI with premedication. CONCLUSION: HBI is still the
most effective and efficient way to palliate pain from widely disseminated cancer.
Fractionating HBI eliminates need for the premedication and close patient monitoring
required for SD-HBI. It also allows for an increase in total dose which can produce better
responses in pain relief, duration of relief, PFS, OS, and quality of life.
Strontium-89--precursor targeted therapy for pain relief of blastic
metastatic disease.
Robinson RG Cancer 1993 Dec 1;72(11 Suppl):3433-3435
Strontium-89 is a radioactive calcium analog that provides an energetic beta particle for
radiation therapy of osteoblastic disease. Strontium-89 is used as palliative therapy with
the primary goal being pain relief. More than 500 patients with painful blastic
metastatic disease were treated at University of Kansas Medical Center Improvement
(decrease in pain, increase in physical activity level) was noted in 80% of patients with
prostate carcinoma and 81% of patients with metastatic breast cancer to bone.
Marrow toxicity levels were acceptable. The therapy can be repeated at 3-month intervals.
Strontium-89 is a safe and effective systemic therapy for painful blastic metastatic
disease. There is no longer any reason why the vast majority of persons with painful
blastic metastatic disease should continue to hurt.
BRAIN METASTASES
An overview of radiotherapy trials for the treatment of brain metastases.
Berk L Oncology (Huntingt) 1995 Nov;9(11):1205-1212
Critical analysis of relevant randomized trials indicated that radiation therapy can
effectively palliate the symptoms of brain metastases. Prognostic factors for improved
survival are good performance status and the absence of a non-central nervous system
tumor. The most efficient treatment protocol is controversial, but the literature
supports the use of 20 Gy in five fractions for the treatment of patients with a poor
prognosis. Patients with a solitary brain metastasis and no systemic disease benefit
from resection of the brain metastasis followed by postoperative radiation.
Radiotherapy for cerebral metastases.
Sneed PK, Larson DA, Wara WM Neurosurg Clin N Am 1996 Jul;7(3):505-515
Whole brain radiotherapy (WBRT) for patients with unresected brain metastases results in symptomatic
response in about 50% of patients and improvement in median survival to 3 to 6
months. Most patients with brain metastases are appropriately treated with a
conventional palliative course of 30 Gy in 10 fractions over 2 weeks,
although accelerated hyperfractionation with 32 Gy to the whole brain plus a boost to at
least 54.4 Gy at 1.6 Gy twice daily yields better results for patients with solitary
metastases. Patients with a life-expectancy of greater than 6 months should receive at
most that or equal to 2.0 Gy per fraction to minimize the risk of radiation-induced
leukoencephalopathy and dementia. Patients with good performance status, absent or
controlled primary tumor, and no extracranial metastases might benefit from surgical
resection or radiosurgery (with or without adjunctive WBRT) to improve local control.
A randomized phase III study of accelerated hyperfractionation versus
standard in patients with unresected brain metastases: a report of the Radiation Therapy
Oncology Group (RTOG) 9104.
Murray KJ, Scott C, Greenberg HM, Emami B, Seider M, Vora NL, Olson C, Whitton A, Movsas
B, Curran W Int J Radiat Oncol Biol Phys 1997 Oct 1;39(3):571-574
PURPOSE: To compare 1-year survival and acute toxicity rates between an accelerated
hyperfractionated (AH) radiotherapy (1.6 Gy b.i.d.) to a total dose of 54.4 Gy vs. an
accelerated fractionation (AF) of 30 Gy in 10 daily fractions in patients with unresected
brain metastasis. Of the 429 eligible and analyzable patients, the median survival time
was 4.5 months in both arms. The 1-year survival rate was 19% in the AF arm vs. 16% in
the AH arm. No difference in median or 1-year survival was observed among patients with
solitary metastasis between treatment arms. This randomized comparison could not
demonstrate any improvement in survival when compared to a conventional regimen of 30 Gy
in 10 fractions. Therefore, this accelerated hyperfractionated regimen to 54.4 Gy
cannot be recommended for patients with intracranial metastatic disease.
Analysis of outcome in patients reirradiated for brain metastases.
Wong WW, Schild SE, Sawyer TE, Shaw EG Int J Radiat Oncol Biol Phys 1996
Feb 1;34(3):585-590
This retrospective study examines our experience with reirradiation of patients for
progressive brain metastases after an initial+ course of WBRT. The median dose of the
first course of irradiation was 30 Gy (range: 1.5-50.6 Gy). The median dose of the second
course of irradiation was 20 Gy (range: 8.0-30.6 Gy). RESULTS: Twenty-three patients
(27%) had resolution of neurologic symptoms, 37 patients (43%) had partial improvement of
neurologic symptoms, and 25 patients (29%) had either no change or worsened after
reirradiation. The median survival following reirradiation was 4 months (range:
0.25-72 months). The majority of patients had no significant toxicity secondary to
reirradiation. Reirradiation should be offered to patients who develop progressive brain
metastases.
HEPATIC METASTASES
A comparison of misonidazole sensitized radiation therapy to radiation
therapy alone for the palliation of hepatic metastases: results of a Radiation Therapy
Oncology Group randomized prospective trial.
Leibel SA, Pajak TF, Massullo V, Order SE, Komaki RU, Chang CH, Wasserman TH, Phillips TL,
Lipshutz J, Durbin LM, nt J Radiat Oncol Biol Phys 1987 Jul;13(7):1057-1064
Two hundred fourteen patients were accessioned to this study of whom 187 were evaluable.
Radiation therapy was delivered to the whole liver to a dose of 21.0 Gy in 7 fractions.
The addition of misonidazole did not significantly improve the therapeutic response to
radiation therapy in any of the parameters studied. Hepatic irradiation was
effective in relieving abdominal pain with 80% of the symptomatic patients achieving
improvement following therapy. Pain was completely relieved in 54% of these patients.
Palliation of pain was prompt, occurring within a median of 1.7 weeks from the
initiation of treatment, and 94% of patients who improved did so within 6 weeks of
treatment. The median duration of response was 13.0 weeks in the symptomatic
patients; 52% of those surviving 3 months remained improved. KPS improved in 28% of
patients. Serial CT scans revealed a partial response in 7% and a marginal response in 13%
of patients. One patient had a complete response to treatment. The median survival
of patients treated in this series was 4.2 months There was no significant
treatment related morbidity. Radiation therapy remains an excellent palliative tool for
the management of patients with symptomatic hepatic metastases. Further research must
continue to identify new methods of selectivity enhancing the tumor response to radiation
therapy.
LUNG CANCER
Palliative radiotherapy for inoperable carcinoma of the lung: final
report of a RTOG multi-institutional trial.
Simpson JR, Francis ME, Perez-Tamayo R, Marks RD, Rao DV, Int J Radiat Oncol Biol Phys
1985 Apr;11(4):751-758
Between June 1973 and February 1979,
409 patients with inoperable advanced non-oat cell carcinoma of the lung were
randomized on RTOG protocol 73-02. Three treatment arms were evaluated: 40 Gy split
course, 30 Gy continuous course, and 40 Gy continuous course. Patients were also
randomized to receive cytoxan or no further therapy following irradiation. Three hundred
sixteen patients were evaluable. Palliation of symptoms was achieved in 60% with 1/4
of the patients becoming symptom-free. Complete regression of local and regional tumor was
produced in 15% and partial regression in 26%. There is no significant difference
between the treatment arms in these objective response rates. Median survival times
were approximately 6 months. Significant toxicity occurred in fewer than 6% of
patients.
A randomized study on palliative radiation therapy for inoperable non
small cell carcinoma of the lung.
Teo P, Tai TH, Choy D, Tsui KH, Int J Radiat Oncol Biol Phys 1988 May;14(5):867-871
Between October 1981 and November 1984, 291 patients with inoperable advanced non-small
cell carcinoma of the lung (NSCLC) were randomized to a two-arm study. Without
correction for lung attenuation 45 Gy/18 fractions/4 1/2 weeks were given in arm 1 and
31.2 Gy/4 fractions/4 weeks were given in arm 2. Prognosis was poor with an overall median
survival of 20 weeks and was similar in both arms. Radiological tumor response was
also similar: 53% in arm 1 and 50% in arm 2. However arm 1 was superior than arm
2 in achieving symptom palliation, 71% vs 54%, p less than 0.02. Treatment
complications were mild and included mainly radiation oesophagitis and pneumonitis and
pulmonary fibrosis. Treatments in both arms were equally well tolerated.
PELVIC CANCERS
Palliative radiotherapy for ovarian cancer.
Adelson MD, Wharton JT, Delclos L, Copeland L, Gershenson D, Int J Radiat Oncol Biol
Phys 1987 Jan;13(1):17-21
Large single-fraction irradiation is effective palliation for advanced ovarian cancer.
It has an acceptable complication rate and requires only a limited number of visits (i.e.,
one treatment per 4-week course) to administer. Forty-two patients received single or
multiple fractions of (three maximum) 10 Gray (Gy) to the pelvis. Forty patients had
received preirradiation chemotherapy. Tumor size before and after radiotherapy was
evaluable in 34 patients and decreased in 25. Bleeding decreased or stopped in 15 of 21
patients, and pain lessened or ceased in 11 of 20 patients. Thirteen patients had
surgical procedures performed after irradiation therapy. Ten had gastrointestinal
procedures, and in six radiation injury was believed to be the main contributor to
complication. Hemorrhagic cystitis or proctitis occurred 6 to 18 months after irradiation
in four patients. Three of these four patients received three 10 Gy fractions. The safest
and most efficient dose may be one or two fractions, since three 10 Gy fractions may not
increase palliation.
Palliation of advanced pelvic malignant disease with large fraction
pelvic radiation and misonidazole: final report of RTOG phase I/II study.
Spanos WJ Jr, Wasserman T, Meoz R, Sala J, Kong J, Stetz J, nt J Radiat Oncol Biol Phys
1987 Oct;13(10):1479-1482
Between October 1979 and June 1982 forty-six patients were entered on a non-randomized
Phase I-II protocol for the evaluation of Misonidazole combined with high dose per
fraction radiation for the treatment of advanced pelvic malignancies. Pelvic
radiation consisted of 1000 cGy in one fraction repeated at 4-week intervals for a
total of three treatments. The distribution of histology consisted of 20
gynecologic, 24 bowel, and 2 prostate malignancies. Of the thirty-seven patients
completing the three treatments; there were 6 complete responses (14% CR), 10
partial responses (27% PR) 19 minimal or no response (32% NR), and 4 unevaluable.
One patient remains NED 5.5 years following radiation. Radiation toxicity was significant
for late bowel damage. There were 4 (11%) Grade 3 and 7 (19%) Grade 4 gastro-intestinal
(GI) toxicities. Because of the GI complication rate, this protocol for palliation
of advanced pelvic malignancies has been replaced by a protocol that uses 4 fractions over
2 days (b.i.d.) of 370 cGy per fraction repeated at 3-week intervals for a total of 3
courses.
Late effect of multiple daily fraction palliation schedule for advanced
pelvic malignancies (RTOG 8502).
Spanos WJ Jr, Clery M, Perez CA, Grigsby PW, Doggett RL, Poulter CA, Steinfeld AD, Int
J Radiat Oncol Biol Phys 1994 Jul 30;29(5):961-967
Prospective evaluation of a palliative radiation schedule for advanced pelvic malignancies
was conducted from 1985 to 1989 by RTOG 8502. The dose was 44.40 Gy in 12 fractions
(3.7 Gy BID) with a rest after 14.80 Gy and 29.60 Gy. The pilot part of the study
allowed for a variable rest interval of 3-6 weeks. The rest interval was then randomized
between 2 and 4 weeks to determine effect on tumor control. No difference in tumor control
was identified The crude late complications rate is 6%. Actuarial analysis using
cumulative incidence shows 6.9% by 18 months. This represents a significant decrease in
late complications from 49% seen with higher dose per fraction (10 Gy x 3) piloted by
Radiation Therapy Oncology Group (7905) for a similar group of patients. Long-term
analysis of late complication indicates this schedule can be used in the pelvis with
relatively low incidence of complication. This schedule has significant logistic benefits
and has been shown to produce good tumor regression and excellent palliation of symptoms.
Radiation palliation of cervical cancer.
Spanos WJ Jr, Pajak TJ, Emami B, Rubin P, Cooper JS, Russell AH, Cox JD, J Natl Cancer
Inst Monogr 1996;21:127-130
Two radiation schedules have been reported on for the treatment of advanced pelvic disease
including cervical cancer. The large single-dose schedule consisted of 10-Gy fractions
repeated at monthly intervals to a maximum of 30 Gy. This schedule has produced good
palliative results with symptomatic improvement in approximately 50% of patients and
objective response in 35%-80%. However, severe late toxicity was shown to be as high as
42% (actuarial). The second schedule tested by the Radiation Therapy Oncology Group
consisted of 3.7-Gy fractions given twice a day for 2 days (14.8 Gy) repeated after
2-4 weeks for a maximum of 44.4 Gy. There were 284 patients accrued, and the subgroup of
61 cervical cancer patients is analyzed in this article. The subjective response (50%-100%
complete response) and objective response (53%) were similar to those observed with the
large single-fraction schedule. The late toxicity was significantly lower (7%-actuarial).
For patients who may survive 6 months or longer, this second schedule is preferable.
Phase II study of multiple daily fractionations in the palliation of
advanced pelvic malignancies: preliminary report of RTOG 8502.
Spanos W Jr, Guse C, Perez C, Grigsby P, Doggett RL, Poulter C, Int J Radiat Oncol Biol
Phys 1989 Sep;17(3):659-661
This Phase II protocol was designed around the format of a previously reported study for
the palliation of advanced pelvic malignancies (RTOG 7905). The large dose per fraction
(1000 cGy) of the first study unexpectedly demonstrated frequent late gastrointestinal
toxicity and was replaced in the present study by 2 days of twice daily fractionation (370
cGy/fraction totaling 1480 cGy/course) based on linear quadratic consideration of
acute and late toxicities. The interval between courses of 4 weeks was retained and the
total dose for three courses was 4440 cGy. A total of 152 patients were entered of
which 142 have sufficient follow-up information for analysis. Fifty-nine percent of the
patients completed all three courses, 20% completed two courses, and 20% received only one
course. The primary sites were: gynecological (39.4%); colorectal (32.4%); genitourinary
(24.7%); and other (2.8%). The best overall response was: complete remission (10%);
partial remission (22%); no change (24%); progression (10%); and unknown (27%). For the
patients completing all three courses, the response was: complete remission (14%); partial
remission (31%); no change (40%); progression (7%); and unknown (8%). Median survival
was 4.5 months and the actuarial survival at 12 months is 19%.
Palliative reirradiation for recurrent rectal cancer.
Lingareddy V, Ahmad NR, Mohiuddin M, Int J Radiat Oncol Biol Phys 1997 Jul 1;38(4):785-790
PURPOSE: The purpose of this study was to analyze the efficacy and acute and late toxicity
of reirradiation for recurrent rectal cancer. . Median initial RT dose to the
pelvis was 50.4 Gy. Median reirradiation dose was 30.6 Gy. The RTOG Grade 3 acute
toxicity rate was 31%. The RTOG Grade 3 and 4 late toxicity rates were 23 and 10%,
respectively. On multivariate analysis, the only factor associated with reduced late
toxicity was hyperfractionated delivery of reirradiation. Bleeding, pain, and mass
effect were palliated completely in 100, 65, and 24% of instances, respectively, and the
majority of responding patients were palliated until death. The overall median survival
time from retreatment was 12 months. The 2- and 3-year overall actuarial survival
rates were 25 and 14%, respectively.