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Prophylactic pelvic girdle irradiation in the treatment of prostatic carcinoma
Inr. J. Radiation Oncology Btol. Phys.. Vol 7. pp. 81 l-81 9 Pnnkd in Ihe U.S.A. All rights merved.
03~3016/81/060817-03502.00/0 Pras Ltd. Copyright 8 198
I Pcrprnon
??Brief Communication PROPHYLACTIC
PELVIC GIRDLE IRRADIATION IN THE TREATMENT OF PROSTATIC CARCINOMA
TAPAN Virginia Commonwealth
A.
HAZRA,
M.D.
AND SHANKAR GIRI,
M.D.
University, Medical College of Virginia, Department of Radiology, Division of Radiation Therapy and Oncology, Rikhmond, VA 23298
This is a report of a pilot study of the effectiveness of irrailiation therapy to the pelvic girdle in decreasing the incidence of hony metastases in patients with prostatic cancer4Thirty-two patients were entered in the study; none of them failed in the pelvic bones total tumor dose of 6800 rad was delivered, the non-conventionalfractionation scheme used in this pelvic nodes received 5000 rad and the pelvic girdle 800 rad. study diminishes tbe incidence of osseous unacceptable bowel injury. Forty-three’percentof patients bad pro&is and 20 % Prostatic, Prophylactic, Axial.
important route involved in the metastatic spread; (4) the radiobiological evidence’ suggested that a single dose of 300 rad has a cell lethality of 90% however at 800 rad, the cell kill is 99.5% or better. If the above assumptions regarding the metastatic spread from carcinoma of the prostate to the bone and the ability of 800 rad to kill 99.5% of cells are true, then a single dose of 800 rad to the pelvic girdle along with irradiation to the prostate and the regional nodes should result in an improved disease free survival rate. Furthermore, such a study will also result in information regarding the cascade process of metastatic spread, tolerance of small and large bowel, and tolerance of the bladder to non-conventional fractionation schedule.
INTRODUCTION The role of radiation therapy in the control of localized prostatic cancer has been demonstrated by various authors.6.7.8*‘0In spite of adequate local control, most patients with carcinoma of the prostate fail with bony metastasis. Minimal information is available regarding the role of extended field’” or prophylactic axial skeletal irradiation therapy in diminishing the incidence of skeletal metastasis and improving the survival rate. A pilot study was designed in October of 1976 at our Center to study the effectiveness of a single dose of radiation therapy to the pelvic girdle (pelvic bones, upper end of femur, and lower lumbar spine), in combination with irradiation to the prostate gland and the regional nodes, in improving local control and preventing osseous metastasis. The basis for this study were (1) Batson’s postulation’ that metastatic disease to the bones from prostatic carcinoma occurs through the vertebral venous plexus and its extensive communication with the caval system; (2) Franks4 in an autopsy series, demonstrated that an overwhelming majority of patients with osseous metastasis have involvement of the pelvic girdle; (3) Varkarakis et al..‘* suggested that prostatic carcinoma spreads by a cascade phenomenon and that there are.two major routes of metastatic spread: one involves the lymphatic system with spread to the regional lymph nodes, the other involves a venous system with metastatic spread to the pelvic bones. On the basis of the limited material. they could not conclude which was the more
METHODS AND MATERIALS Thirty-two patients with histologically proven adenocarcinoma of the prostate were entered into the study between October, 1976 to November, 1977. All patients were followed for at least 30 months after completion of treatment, or until death. Patient characteristics There were 17 white patients and 15 black patients. Over 80% of the patients were older than 60 years. Following a complete history and physical examination, a metastatic work-up which included routine blood chemistries, X ray studies, a technitium polyphosphate bone stun, and a lymphangiogram was carried out. Four
Supported in part by Grant #5-R-25CA22032-4 Awarded by National Cancer Institute, Department of Health, Education and Welfare Reprint requests to: T,A. Hazra, M.D., Professor and Chair-
man, Radiation Therapy and Oncology, Medical College of Virginia, Box 533, Richmond, VA 23298. Accepted for publication 3 I March 198 I.
817
818
Radiation Oncology 0 Biology 0 Physics
patients had a staging laparotomy. A system of staging as advocated by Whitmore’ was used. Two patients had Stage A disease (clinically latent), nine patients had Stage B disease (tumor confined with the capsule of the prostate), 17 patients had Stage C disease (extracapsular extension or invasion into the seminal vesicles) and all four patients who had staging laparotomy were staged as D, because of involvement of pelvic lymph nodes. Irradiation technique
A single midplane dose of 800 rad was delivered to the pelvic girdle by means of anterior/posterior parallel opposing fields. After a rest period of seven days, radiation therapy to the prostate and the regional nodes was started. A midplane dose of 5000 rad in 25 fractions of 200 each was delivered to the pelvis by a four field technique. All fields were treated daily. The volume irradiated extended from the upper border of the first sacral vertebra to 2.5 ems. below the caudal border of the prostate. Following this a booster dose of 1000 rad in five fractions in five days were delivered to the prostate and the immediate periprostatic tissue. Thus the total tumor dose was 6800 rad. Most patients received treatment by means of a IO MeV linear accelerator except a few who were treated with a cobalt 60 teletherapy unit. RESULTS Thirty of the 32 patients completed their treatment. Of the two patients who did not complete the prescribed treatment, one had to discontinue therapy because of severe diarrhea at. 3000 rad and the other developed diarrhea and rectal bleeding at 3500 rad; his treatment was also discontinued. There were three (10%) deaths amongst the 30 patients who completed their treatment. One patient with Stage C disease developed proctitis six months after completion of therapy and a colostomy was performed. Three months later, as a result of continued rectal bleeding, a resection of the Hartman pouch was attempted. The patient died post-operatively from pulmonary embolism. At autopsy no residual tumor in the prostate or the regional nodes was found. The second patient had Stage C disease and developed metastasis to the left supraclavicular node three months after completion of therapy. He received palliative radiotherapy to the left supraclavicular fossa. Two months after completion of the palliative treatment he developed metastasis to the ribs and skull. At this time he was found to have paralysis of the left hypoglossal nerve, the exact etiology of which could not be determined. Four months after rib and skull metastasis the patient developed bleeding in the rectum along with metastasis to the upper lumbar spine. He then underwent a bilateral orchiectomy with a poor clinical response. He died of pulmonary embolism five months later. The third patient had Stage B disease and developed left side pleural effusion three months after completion of therapy. No tumor cells were found in the pleural fluid. Six months later the patient developed bilateral lower urinary tract obstruction presumably because of the progression of his prostatic cancer. While under
June 1981, Volume7, Number 6 investigation the patient died of a myocardial infarction. One of the three patients developed metastasis within the irradiated pelvic bones. Of the 30 patients who were followed for a minimum of thirty months, two have failed with bony metastasis outside the treated area. One patient failed both locally and with distant bony metastasis. The remaining 28 patients have excellent local control with no evidence of distant metastasis. The acute radiation reactions seen in our patients were minimal and included transient diarrhea, minimal dysuria and lower abdominal discomfort. Major late complications occurred in 19 patients within 6-9 months of completion of therapy and were of sudden onset. These complications consisted of severe rectal problems in the form of bleeding and stricture, necessitating colostomy in six (20%) patients. The remaining 13 patients responded to conservative management. DISCUSSION Ray and Bagshaw” reported the results of treatment with radiation therapy at their institution. In their series of 430 patients, 120 (27.9%) patients failed, the majority of failures occurring within two years. Of these, 60% of patients failed with distant metastasis, 35% failed both locally and distally, and only 9% failed locally. In most of the patients the site of metastasis was usually the pelvic bones. In the present study, four patients (13.3%) failed and the site of failure was outside the field of radiation. One patient failed locally. Of all the patients who failed distally, the site of the first failure was to the bones outside the irradiated volume. No patient developed metastasis either to the lungs or to the liver without a bony metastasis. This lends further credence to the report of Varkarakis et aI.” that the cascade phenomenon is involved in the metastatic spread of carcinoma of the prostate. It appears from the present pilot study that a single fraction of 800 rad to the bony pelvis decreases the incidence of metastatic disease. Four patients developed metastasis outside the radiated volume mainly to the upper lumbar spine. The drawback of this study has been the unacceptable delayed bowel injury. Thirteen patients (43%) had proctitis and six patients (20%) required colostomy because of the progressiveness and severity of the proctitis. In almost all patients, the sigmoid colon showed severe radiation changes. There was no small bowel injury. In conclusion, we feel that a single fraction of 800 rad can prevent subsequent local osseous metastasis. The failure of four patients in the upper lumbar spine indicates that this region has to be included with the pelvic bones in the initial treatment portals. The bowel complications with the present fractionation scheme are unacceptable and can be minimized with more individualized treatment techniques. We feel that development of bony metastases in the pelvic girdle can be forestalled by prophylactic treatment.
Pelvic girdle irradiation in prostatic cancer 0 T.A. HAZRAANDS. GIRI
819
REFERENCES 1. Bagshaw, M.A., Pistenma, D.A., Ray, G.R., Castellino, R.A., Meares, E.H.: Evaluation of extended field radiotherapy for prostatic neoplasm. Progress Report. Cancer Treat. Rep. 61: 297-306,
1977.
2. Batson, O.V.: The role of vertebral veins in metastatic processes. Ann. Int. Med. 16: 38-45, 1942. 3. Fitzpatrick, P.J., Rider, W.D.: Half body radiotherapy. int. J. Radiat. Oncol. Biol. Phys. 1: 197-207, 1976. 4. Franks, L.M.: The spread of prostatic carcinoma to the bones. J. Path. Bact. 66: 91-93, 1953. 5. George, F.W., Cariton, C.E.. Jr., Dyhuizen, R.F.. Dillon, J.R.: Cobalt 60 telecurietherapy in the definitive treatment of carcinoma of the prostate-A preliminary report. J. Vrol. 93: 102-109.1965. 6. Harisiadis, L., Veenema, F.J., Senyszyn, J.J., Puchner. P.J., Tretter, P., Romas, N.A., Chang, C.H., Lattimer, J.K., Tannenbaum, M.: Carcinoma of the prostate. Treatment with external radiotherapy. Cancer 41: 2131-2142, 1978. 7. Hazra, T.A.: Radiotherapy in the treatment of locally
infiltrating carcinoma of the prostate. J. Urof. 108: 460461. 1972. 8. Hiiaris, B.S., Whitmore, W.F., Batata, M., Barzell, W.: Behavioral patterns of prostate adenocarcinoma following an I- 125 implant and pelvic node dissection. int. J. Radiat. Oncol. Biol. Phys. 2: 631-637, 1977. 9. McCulloch, E.A., Till, J.E.: The sensitivity
10.
11.
12.
13.
of cells from normal mouse bone marrow to gamma radiation in vitro and in vivo. Radiut. Res. 16: 822-832. 1962. Pistenma, D.A., Ray, F.R., Bagshaw, M.A.: The role of megavoltage radiation in the treatment of prostatic carcinoma. Semin. Oncol. 3: 115-l 22, 1976. Ray, G.R., Bagshaw, M.A.: The role of radiation therapy in the definitive treatment of adenocarcinoma of the prostate. Ann. Rev. Med. 26: 567-588, 1975. Varkarakis, M.J., Winterberger, A.R., Gaeta, J., Moore, R.H., Murphy, G.P.: Lung metastases in prostatic carcinoma, clinical significance. Urology 3: 447-452, 1974. Whitmore, W.F., Jr.: Hormone therapy in prostatic cancer. Am. J. Med. 21: 697-7 13, 1956.
03~3016/81/060817-03502.00/0 Pras Ltd. Copyright 8 198
I Pcrprnon
??Brief Communication PROPHYLACTIC
PELVIC GIRDLE IRRADIATION IN THE TREATMENT OF PROSTATIC CARCINOMA
TAPAN Virginia Commonwealth
A.
HAZRA,
M.D.
AND SHANKAR GIRI,
M.D.
University, Medical College of Virginia, Department of Radiology, Division of Radiation Therapy and Oncology, Rikhmond, VA 23298
This is a report of a pilot study of the effectiveness of irrailiation therapy to the pelvic girdle in decreasing the incidence of hony metastases in patients with prostatic cancer4Thirty-two patients were entered in the study; none of them failed in the pelvic bones total tumor dose of 6800 rad was delivered, the non-conventionalfractionation scheme used in this pelvic nodes received 5000 rad and the pelvic girdle 800 rad. study diminishes tbe incidence of osseous unacceptable bowel injury. Forty-three’percentof patients bad pro&is and 20 % Prostatic, Prophylactic, Axial.
important route involved in the metastatic spread; (4) the radiobiological evidence’ suggested that a single dose of 300 rad has a cell lethality of 90% however at 800 rad, the cell kill is 99.5% or better. If the above assumptions regarding the metastatic spread from carcinoma of the prostate to the bone and the ability of 800 rad to kill 99.5% of cells are true, then a single dose of 800 rad to the pelvic girdle along with irradiation to the prostate and the regional nodes should result in an improved disease free survival rate. Furthermore, such a study will also result in information regarding the cascade process of metastatic spread, tolerance of small and large bowel, and tolerance of the bladder to non-conventional fractionation schedule.
INTRODUCTION The role of radiation therapy in the control of localized prostatic cancer has been demonstrated by various authors.6.7.8*‘0In spite of adequate local control, most patients with carcinoma of the prostate fail with bony metastasis. Minimal information is available regarding the role of extended field’” or prophylactic axial skeletal irradiation therapy in diminishing the incidence of skeletal metastasis and improving the survival rate. A pilot study was designed in October of 1976 at our Center to study the effectiveness of a single dose of radiation therapy to the pelvic girdle (pelvic bones, upper end of femur, and lower lumbar spine), in combination with irradiation to the prostate gland and the regional nodes, in improving local control and preventing osseous metastasis. The basis for this study were (1) Batson’s postulation’ that metastatic disease to the bones from prostatic carcinoma occurs through the vertebral venous plexus and its extensive communication with the caval system; (2) Franks4 in an autopsy series, demonstrated that an overwhelming majority of patients with osseous metastasis have involvement of the pelvic girdle; (3) Varkarakis et al..‘* suggested that prostatic carcinoma spreads by a cascade phenomenon and that there are.two major routes of metastatic spread: one involves the lymphatic system with spread to the regional lymph nodes, the other involves a venous system with metastatic spread to the pelvic bones. On the basis of the limited material. they could not conclude which was the more
METHODS AND MATERIALS Thirty-two patients with histologically proven adenocarcinoma of the prostate were entered into the study between October, 1976 to November, 1977. All patients were followed for at least 30 months after completion of treatment, or until death. Patient characteristics There were 17 white patients and 15 black patients. Over 80% of the patients were older than 60 years. Following a complete history and physical examination, a metastatic work-up which included routine blood chemistries, X ray studies, a technitium polyphosphate bone stun, and a lymphangiogram was carried out. Four
Supported in part by Grant #5-R-25CA22032-4 Awarded by National Cancer Institute, Department of Health, Education and Welfare Reprint requests to: T,A. Hazra, M.D., Professor and Chair-
man, Radiation Therapy and Oncology, Medical College of Virginia, Box 533, Richmond, VA 23298. Accepted for publication 3 I March 198 I.
817
818
Radiation Oncology 0 Biology 0 Physics
patients had a staging laparotomy. A system of staging as advocated by Whitmore’ was used. Two patients had Stage A disease (clinically latent), nine patients had Stage B disease (tumor confined with the capsule of the prostate), 17 patients had Stage C disease (extracapsular extension or invasion into the seminal vesicles) and all four patients who had staging laparotomy were staged as D, because of involvement of pelvic lymph nodes. Irradiation technique
A single midplane dose of 800 rad was delivered to the pelvic girdle by means of anterior/posterior parallel opposing fields. After a rest period of seven days, radiation therapy to the prostate and the regional nodes was started. A midplane dose of 5000 rad in 25 fractions of 200 each was delivered to the pelvis by a four field technique. All fields were treated daily. The volume irradiated extended from the upper border of the first sacral vertebra to 2.5 ems. below the caudal border of the prostate. Following this a booster dose of 1000 rad in five fractions in five days were delivered to the prostate and the immediate periprostatic tissue. Thus the total tumor dose was 6800 rad. Most patients received treatment by means of a IO MeV linear accelerator except a few who were treated with a cobalt 60 teletherapy unit. RESULTS Thirty of the 32 patients completed their treatment. Of the two patients who did not complete the prescribed treatment, one had to discontinue therapy because of severe diarrhea at. 3000 rad and the other developed diarrhea and rectal bleeding at 3500 rad; his treatment was also discontinued. There were three (10%) deaths amongst the 30 patients who completed their treatment. One patient with Stage C disease developed proctitis six months after completion of therapy and a colostomy was performed. Three months later, as a result of continued rectal bleeding, a resection of the Hartman pouch was attempted. The patient died post-operatively from pulmonary embolism. At autopsy no residual tumor in the prostate or the regional nodes was found. The second patient had Stage C disease and developed metastasis to the left supraclavicular node three months after completion of therapy. He received palliative radiotherapy to the left supraclavicular fossa. Two months after completion of the palliative treatment he developed metastasis to the ribs and skull. At this time he was found to have paralysis of the left hypoglossal nerve, the exact etiology of which could not be determined. Four months after rib and skull metastasis the patient developed bleeding in the rectum along with metastasis to the upper lumbar spine. He then underwent a bilateral orchiectomy with a poor clinical response. He died of pulmonary embolism five months later. The third patient had Stage B disease and developed left side pleural effusion three months after completion of therapy. No tumor cells were found in the pleural fluid. Six months later the patient developed bilateral lower urinary tract obstruction presumably because of the progression of his prostatic cancer. While under
June 1981, Volume7, Number 6 investigation the patient died of a myocardial infarction. One of the three patients developed metastasis within the irradiated pelvic bones. Of the 30 patients who were followed for a minimum of thirty months, two have failed with bony metastasis outside the treated area. One patient failed both locally and with distant bony metastasis. The remaining 28 patients have excellent local control with no evidence of distant metastasis. The acute radiation reactions seen in our patients were minimal and included transient diarrhea, minimal dysuria and lower abdominal discomfort. Major late complications occurred in 19 patients within 6-9 months of completion of therapy and were of sudden onset. These complications consisted of severe rectal problems in the form of bleeding and stricture, necessitating colostomy in six (20%) patients. The remaining 13 patients responded to conservative management. DISCUSSION Ray and Bagshaw” reported the results of treatment with radiation therapy at their institution. In their series of 430 patients, 120 (27.9%) patients failed, the majority of failures occurring within two years. Of these, 60% of patients failed with distant metastasis, 35% failed both locally and distally, and only 9% failed locally. In most of the patients the site of metastasis was usually the pelvic bones. In the present study, four patients (13.3%) failed and the site of failure was outside the field of radiation. One patient failed locally. Of all the patients who failed distally, the site of the first failure was to the bones outside the irradiated volume. No patient developed metastasis either to the lungs or to the liver without a bony metastasis. This lends further credence to the report of Varkarakis et aI.” that the cascade phenomenon is involved in the metastatic spread of carcinoma of the prostate. It appears from the present pilot study that a single fraction of 800 rad to the bony pelvis decreases the incidence of metastatic disease. Four patients developed metastasis outside the radiated volume mainly to the upper lumbar spine. The drawback of this study has been the unacceptable delayed bowel injury. Thirteen patients (43%) had proctitis and six patients (20%) required colostomy because of the progressiveness and severity of the proctitis. In almost all patients, the sigmoid colon showed severe radiation changes. There was no small bowel injury. In conclusion, we feel that a single fraction of 800 rad can prevent subsequent local osseous metastasis. The failure of four patients in the upper lumbar spine indicates that this region has to be included with the pelvic bones in the initial treatment portals. The bowel complications with the present fractionation scheme are unacceptable and can be minimized with more individualized treatment techniques. We feel that development of bony metastases in the pelvic girdle can be forestalled by prophylactic treatment.
Pelvic girdle irradiation in prostatic cancer 0 T.A. HAZRAANDS. GIRI
819
REFERENCES 1. Bagshaw, M.A., Pistenma, D.A., Ray, G.R., Castellino, R.A., Meares, E.H.: Evaluation of extended field radiotherapy for prostatic neoplasm. Progress Report. Cancer Treat. Rep. 61: 297-306,
1977.
2. Batson, O.V.: The role of vertebral veins in metastatic processes. Ann. Int. Med. 16: 38-45, 1942. 3. Fitzpatrick, P.J., Rider, W.D.: Half body radiotherapy. int. J. Radiat. Oncol. Biol. Phys. 1: 197-207, 1976. 4. Franks, L.M.: The spread of prostatic carcinoma to the bones. J. Path. Bact. 66: 91-93, 1953. 5. George, F.W., Cariton, C.E.. Jr., Dyhuizen, R.F.. Dillon, J.R.: Cobalt 60 telecurietherapy in the definitive treatment of carcinoma of the prostate-A preliminary report. J. Vrol. 93: 102-109.1965. 6. Harisiadis, L., Veenema, F.J., Senyszyn, J.J., Puchner. P.J., Tretter, P., Romas, N.A., Chang, C.H., Lattimer, J.K., Tannenbaum, M.: Carcinoma of the prostate. Treatment with external radiotherapy. Cancer 41: 2131-2142, 1978. 7. Hazra, T.A.: Radiotherapy in the treatment of locally
infiltrating carcinoma of the prostate. J. Urof. 108: 460461. 1972. 8. Hiiaris, B.S., Whitmore, W.F., Batata, M., Barzell, W.: Behavioral patterns of prostate adenocarcinoma following an I- 125 implant and pelvic node dissection. int. J. Radiat. Oncol. Biol. Phys. 2: 631-637, 1977. 9. McCulloch, E.A., Till, J.E.: The sensitivity
10.
11.
12.
13.
of cells from normal mouse bone marrow to gamma radiation in vitro and in vivo. Radiut. Res. 16: 822-832. 1962. Pistenma, D.A., Ray, F.R., Bagshaw, M.A.: The role of megavoltage radiation in the treatment of prostatic carcinoma. Semin. Oncol. 3: 115-l 22, 1976. Ray, G.R., Bagshaw, M.A.: The role of radiation therapy in the definitive treatment of adenocarcinoma of the prostate. Ann. Rev. Med. 26: 567-588, 1975. Varkarakis, M.J., Winterberger, A.R., Gaeta, J., Moore, R.H., Murphy, G.P.: Lung metastases in prostatic carcinoma, clinical significance. Urology 3: 447-452, 1974. Whitmore, W.F., Jr.: Hormone therapy in prostatic cancer. Am. J. Med. 21: 697-7 13, 1956.