- Email: [email protected]
Radiation therapy in neuroblastoma
or estrogen therapy experience relief from pain following bilateral adrenalectomy, but whether this is due to elimination of adrenocortical androgens or to corticostrroid replacement therapy remains unclear. Objective regression of the primary tumor or metastases occurs seldom, if at all, and most adrenalectomized patients fail to survive more than one year. Somewhat more encouraging results have been reported following pituitary ablation, particularly in a short-term objective response. Both intrasellar soY, and stereotactic cryohypophysectomy have recently been tried extensively and appear to be as effective as surgical removal of the total gland. Neither adrenalectomy nor hypophysectomy are currently advocated as primary procedures in previously untreated patients, but is reserved rather for those who have relapsed and in whom the disease is progressing actively. Nonhormonal Chemotherapy Alan Yagoda, M.D. Memorial Hospital for Cancer
and Allied Diseases
Many cytotoxic agents alone, or in combination (sometimes with androgens), have been tried with some objective responses from cyclophosphamide, 5fluorouracil, and aniline mustard. Aniline mustard is unique since appropriately stained tumor cells obtained from bone marrow aspirations may be of predictive value. A review of the various cytotoxic agents used in treating prostate carcinoma was presented emphasizing the difficulties in evaluation and the need for random clinical trials.
Pediatric
Urologic
Cancer
Surgical Treatment of Wilms Tumor Willard E. Goodwin, M.D. University of California, Los Angeles, School of Medicine Surgical treatment should be prompt, radical excision of the kidney with all of its attachments, through a generous abdominal incision which also allows inspection of the opposite kidney. It is important not to try to mobilize the kidney and tumor until arterial and venous blood supply have been ligated. The kidney, including Gerota’s fascia and the upper ureter, are removed intact, and lymph nodes are dissected from the diaphragm to the aortic bifurcation. In bilateral disease (4 to 10 per cent) usually one kidney is removed, and the tumor-bearing area in the less involved kidney is marked with silver clips or wire to guide the radiologist for subsequent x-ray therapy. Preoperative irradiation is rarely indicated, but preand postoperative chemotherapy is of definite value. The most useful drugs are Actinomycin D and vincristine. The surgical treatment of nephroblastoma is not an emergency, but it should be performed promptly within a day or two of diagnosis, after chemotherapy is begun.
UROLOGY
/
MAY 1973
/
VOLUME
I, NUMBER 5
_
Chemotherapy in Wilms’ Tumor Wataru W. Sutow, M.D. M.D. Anderson Hospital and Tumor Institute The routine use of adjuvant chemotherapy has improved survival so that now, in favorable cases, a cure rate exceeding 90 per cent can be anticipated. Also, increasing numbers of children with metastatic disease are being saved. Actinomycin-D and vincristine are effective chemotherapeutic agents in treatment of this tumor. The possibility of achieving an additive therapeutic effect by the combination of the two drugs is being evaluated in a national study. The effectiveness of other drug regimens, such as high-dosage cyclophosphamide and adriamycin, remains to be established. Radiation Therapy in Management of Children with Wilms’ Tumor Guilio J. D’Angio, M.D. Memorial Hospital for Cancer and Allied Diseases The role of radiation therapy in the management of children with Wilms’ tumor is undergoing reassessment. The traditional method of treating these patients has included the routine use of postoperative radiation therapy. This has been brought into question recently, and the matter is under investigation by a national cooperative study group. However, radiation therapy undoubtedly is useful in the management of children with metastases. Treatment of Neuroblastoma Alexander H. Bill, M.D. The Children’s Orthopedic Hospital Center, Seattle
and Medical
Neuroblastoma is unusual in that spontaneous regression occurs in a small proportion of the younger patients. Additionally, the disease can be followed by the level of vanillylmandelic acid in the urine, which reflects the amount of tumor tissue. An explanation for the regression has apparently been found. It has been shown in a number of ways by a group of investigators in Seattle that (1) the lymphocytes of the patients and of some family members are lethal to neuroblastoma cells in tissue culture; and (2) possibly more important is the fact that there has been demonstrated a “blocking antibody” in the serum. This blocking antibody evidently protects the tumor cells against the patient’s immune blood cells. Treatment currently is by surgical intervention, radiation, and chemotherapy. The surgical procedure should be carried out to remove as much tumor as possible without loss of function and should be repeated if more tumor appears which can be removed. The judgment as to recurrent tumor is made by following the levels of vanillylmandelic acid, physical examination, and x-ray examination. Radiation Therapy in Neuroblastoma Guilio J. D’Angio, M.D. Memorial Hospital for Cancer and Allied Diseases The role of radiation therapy in the management of patients with neuroblastoma remains to be defined
495
with precision. The vagaries of the tumor and its clinical evolution must be understood before recommendations are made regarding therapy. A staging system, recently suggested by Evans and coworkers, demonstrates the inverse relationship between age and prognosis and identifies a subgroup of patients with disseminated disease who, paradoxically, have excellent survival expectancy. These data, together with experience accumulated by Koop were presented to support recommendations regarding radiation therapy. The withholding of radiation therapy from babies with localized tumors was defended. Chemotherapy of Neuroblastoma Donald Pinkel, M.D. St. Jude Children’s Research Hospital,
Memphis
Three drugs currently in use for chemotherapy of childhood cancer produce partial regression of tumor in some patients with neuroblastoma. Cyclophosphamide, an alkylating agent, is the most effective of the three. It produces significant objective tumor regression in approximately one half of the children. Its administration is. limited by hematopoietic suppression, impairment of nutrition, and emergence of resistant tumor. Vincristine, a natural alkaloid, and daxorubicin (Adriamycin), an antibiotic, produce significant temporary tumor regressions in approximately one fourth of the patients. Vincristine causes peripheral neuropathy, and Adriamycin causes hematosuppression and ulcerative stomatitis. Tumor resistance occurs rapidly to both drugs. The administration of cyclophosphamide and vincristine to children with regional and generalized neuroblastoma, after surgical and radiation therapy, prolongs survival. In infants less than one year of age, the prolonged survival rate is associated with a reduced mortality rate. In older children the fatality rate is not perceptibly influenced. The usefulness of these drugs as adjuvant chemotherapy after removal and/or radiotherapy of localized neuroblastoma is not known. Diagnosis and Treatment of Cancer of the Testis and Paratesticular Tissues Philip R. Exelby, M.D. Memorial Hospital for Cancer and Allied Diseases During a thirty-year period, 1942 to 1971, 63 children were treated at Memorial Hospital for cancer of the testis or paratesticular tissues. Twenty-four were diagnosed as embryonal adenocarcinoma, 14 as teratocarcinoma, and 24 paratesticular rhabdomyosarcoma. Embryonal adenocarcinoma was seen largely in infants, whereas teratocarcinoma was more common after puberty. Rhabdomyosarcoma showed a diphasic age distribution, one group occurring in infancy and early childhood and a second group in adolescence. All the tumors presented as a scrotal mass and were usually clinically indistinguishable at the time of diagnosis. Current management consists of establishing histologic diagnosis by trans-inguinal biopsy. Embryonal adenocarcinoma and teratocarcinoma are treated by
496
radical orchiectomy and retroperitoneal node dissection. Pelvic and retroperitoneal lymph node dissection should be added to orchiectomy in the boys with rhabdomyosarcoma. Postoperative irradiation therapy is given when margins of resection or lymph nodes are positive for tumor. All children would receive four-drug chemotherapy for two years following the surgical procedure. Chemotherapy of Urologic Embryonal Rhabdomyosarcoma in Children Fereshteh Ghavimi, M.D. Memorial Hospital for Cancer and Allied Diseases A review of 27 children, ages nine months to fourteen years, with the diagnosis of embryonal rhabdomyosarcoma of the genitourinary tract and pelvis, treated from 1960 to 1972 at Memorial Hospital is presented. The primary sites were: vagina 2, uterus 2, prostate 3, bladder 3, soft tissue of pelvis 6, and paratesticular 11. The patients were divided into 4 groups based on the extent of the disease at the time of admission to this hospital: I -localized tumor completely resected (13), II-tumor incompletely resected (6), III regional node involvement and incomplete resection of the tumor (5), IV-distant metastases present (3). Seventeen children are alive and free of disease from one and one-half to ten years (median four years), 12 of 13 in group I, 3 of 6 in group II, and 2 of 5 in group III. Fifteen of 17 survivors were treated with a combination of surgery * radiation therapy +- chemotherapy. Beginning in 1970 an integrated protocol of surgery, radiotherapy, and a four-drug regimen has been designed for treatment of this tumor in children. The sequence is concurrent administration of dactinomycin and radiotherapy followed by adriamycin, vincristine, and cyclophosphamide during a threemonth period. The chemotherapy is recycled for two years. Six of the 27 patients have been treated with this combination, and four of them remain free of disease from one and one-half to two and one-half years. These results suggest that early aggressive combined therapy consisting of radical surgery, postoperative radiation, and multidrug therapy can be expected to improve the survival rate. Surgery of Bladder and Prostatic Neoplasms Children H. William Clatworthy, Jr., M.D. Ohio State University College of Medicine
in
Rhabdomyosarcoma is a common malignant softtissue tumor in children, This tumor was found in the bladder or prostate in 12 of 67 patients recently treated at Children’s Hospital, Columbus, Ohio (6 are surviving). Until recently and regardless of the primary site, the reports of successful treatment of this aggressive embryonal neoplasm have been limited to a small series or to isolated cases treated by radical mutilative surgical procedures. Now, a combined therapy, which has proved effective in Wilms’ tumor, utilizing “reasonable surgical procedures” (excision of all
UROLOGY
/
MAY 1973
/
VOLUME
I, NUMBER 5
and Allied Diseases
Many cytotoxic agents alone, or in combination (sometimes with androgens), have been tried with some objective responses from cyclophosphamide, 5fluorouracil, and aniline mustard. Aniline mustard is unique since appropriately stained tumor cells obtained from bone marrow aspirations may be of predictive value. A review of the various cytotoxic agents used in treating prostate carcinoma was presented emphasizing the difficulties in evaluation and the need for random clinical trials.
Pediatric
Urologic
Cancer
Surgical Treatment of Wilms Tumor Willard E. Goodwin, M.D. University of California, Los Angeles, School of Medicine Surgical treatment should be prompt, radical excision of the kidney with all of its attachments, through a generous abdominal incision which also allows inspection of the opposite kidney. It is important not to try to mobilize the kidney and tumor until arterial and venous blood supply have been ligated. The kidney, including Gerota’s fascia and the upper ureter, are removed intact, and lymph nodes are dissected from the diaphragm to the aortic bifurcation. In bilateral disease (4 to 10 per cent) usually one kidney is removed, and the tumor-bearing area in the less involved kidney is marked with silver clips or wire to guide the radiologist for subsequent x-ray therapy. Preoperative irradiation is rarely indicated, but preand postoperative chemotherapy is of definite value. The most useful drugs are Actinomycin D and vincristine. The surgical treatment of nephroblastoma is not an emergency, but it should be performed promptly within a day or two of diagnosis, after chemotherapy is begun.
UROLOGY
/
MAY 1973
/
VOLUME
I, NUMBER 5
_
Chemotherapy in Wilms’ Tumor Wataru W. Sutow, M.D. M.D. Anderson Hospital and Tumor Institute The routine use of adjuvant chemotherapy has improved survival so that now, in favorable cases, a cure rate exceeding 90 per cent can be anticipated. Also, increasing numbers of children with metastatic disease are being saved. Actinomycin-D and vincristine are effective chemotherapeutic agents in treatment of this tumor. The possibility of achieving an additive therapeutic effect by the combination of the two drugs is being evaluated in a national study. The effectiveness of other drug regimens, such as high-dosage cyclophosphamide and adriamycin, remains to be established. Radiation Therapy in Management of Children with Wilms’ Tumor Guilio J. D’Angio, M.D. Memorial Hospital for Cancer and Allied Diseases The role of radiation therapy in the management of children with Wilms’ tumor is undergoing reassessment. The traditional method of treating these patients has included the routine use of postoperative radiation therapy. This has been brought into question recently, and the matter is under investigation by a national cooperative study group. However, radiation therapy undoubtedly is useful in the management of children with metastases. Treatment of Neuroblastoma Alexander H. Bill, M.D. The Children’s Orthopedic Hospital Center, Seattle
and Medical
Neuroblastoma is unusual in that spontaneous regression occurs in a small proportion of the younger patients. Additionally, the disease can be followed by the level of vanillylmandelic acid in the urine, which reflects the amount of tumor tissue. An explanation for the regression has apparently been found. It has been shown in a number of ways by a group of investigators in Seattle that (1) the lymphocytes of the patients and of some family members are lethal to neuroblastoma cells in tissue culture; and (2) possibly more important is the fact that there has been demonstrated a “blocking antibody” in the serum. This blocking antibody evidently protects the tumor cells against the patient’s immune blood cells. Treatment currently is by surgical intervention, radiation, and chemotherapy. The surgical procedure should be carried out to remove as much tumor as possible without loss of function and should be repeated if more tumor appears which can be removed. The judgment as to recurrent tumor is made by following the levels of vanillylmandelic acid, physical examination, and x-ray examination. Radiation Therapy in Neuroblastoma Guilio J. D’Angio, M.D. Memorial Hospital for Cancer and Allied Diseases The role of radiation therapy in the management of patients with neuroblastoma remains to be defined
495
with precision. The vagaries of the tumor and its clinical evolution must be understood before recommendations are made regarding therapy. A staging system, recently suggested by Evans and coworkers, demonstrates the inverse relationship between age and prognosis and identifies a subgroup of patients with disseminated disease who, paradoxically, have excellent survival expectancy. These data, together with experience accumulated by Koop were presented to support recommendations regarding radiation therapy. The withholding of radiation therapy from babies with localized tumors was defended. Chemotherapy of Neuroblastoma Donald Pinkel, M.D. St. Jude Children’s Research Hospital,
Memphis
Three drugs currently in use for chemotherapy of childhood cancer produce partial regression of tumor in some patients with neuroblastoma. Cyclophosphamide, an alkylating agent, is the most effective of the three. It produces significant objective tumor regression in approximately one half of the children. Its administration is. limited by hematopoietic suppression, impairment of nutrition, and emergence of resistant tumor. Vincristine, a natural alkaloid, and daxorubicin (Adriamycin), an antibiotic, produce significant temporary tumor regressions in approximately one fourth of the patients. Vincristine causes peripheral neuropathy, and Adriamycin causes hematosuppression and ulcerative stomatitis. Tumor resistance occurs rapidly to both drugs. The administration of cyclophosphamide and vincristine to children with regional and generalized neuroblastoma, after surgical and radiation therapy, prolongs survival. In infants less than one year of age, the prolonged survival rate is associated with a reduced mortality rate. In older children the fatality rate is not perceptibly influenced. The usefulness of these drugs as adjuvant chemotherapy after removal and/or radiotherapy of localized neuroblastoma is not known. Diagnosis and Treatment of Cancer of the Testis and Paratesticular Tissues Philip R. Exelby, M.D. Memorial Hospital for Cancer and Allied Diseases During a thirty-year period, 1942 to 1971, 63 children were treated at Memorial Hospital for cancer of the testis or paratesticular tissues. Twenty-four were diagnosed as embryonal adenocarcinoma, 14 as teratocarcinoma, and 24 paratesticular rhabdomyosarcoma. Embryonal adenocarcinoma was seen largely in infants, whereas teratocarcinoma was more common after puberty. Rhabdomyosarcoma showed a diphasic age distribution, one group occurring in infancy and early childhood and a second group in adolescence. All the tumors presented as a scrotal mass and were usually clinically indistinguishable at the time of diagnosis. Current management consists of establishing histologic diagnosis by trans-inguinal biopsy. Embryonal adenocarcinoma and teratocarcinoma are treated by
496
radical orchiectomy and retroperitoneal node dissection. Pelvic and retroperitoneal lymph node dissection should be added to orchiectomy in the boys with rhabdomyosarcoma. Postoperative irradiation therapy is given when margins of resection or lymph nodes are positive for tumor. All children would receive four-drug chemotherapy for two years following the surgical procedure. Chemotherapy of Urologic Embryonal Rhabdomyosarcoma in Children Fereshteh Ghavimi, M.D. Memorial Hospital for Cancer and Allied Diseases A review of 27 children, ages nine months to fourteen years, with the diagnosis of embryonal rhabdomyosarcoma of the genitourinary tract and pelvis, treated from 1960 to 1972 at Memorial Hospital is presented. The primary sites were: vagina 2, uterus 2, prostate 3, bladder 3, soft tissue of pelvis 6, and paratesticular 11. The patients were divided into 4 groups based on the extent of the disease at the time of admission to this hospital: I -localized tumor completely resected (13), II-tumor incompletely resected (6), III regional node involvement and incomplete resection of the tumor (5), IV-distant metastases present (3). Seventeen children are alive and free of disease from one and one-half to ten years (median four years), 12 of 13 in group I, 3 of 6 in group II, and 2 of 5 in group III. Fifteen of 17 survivors were treated with a combination of surgery * radiation therapy +- chemotherapy. Beginning in 1970 an integrated protocol of surgery, radiotherapy, and a four-drug regimen has been designed for treatment of this tumor in children. The sequence is concurrent administration of dactinomycin and radiotherapy followed by adriamycin, vincristine, and cyclophosphamide during a threemonth period. The chemotherapy is recycled for two years. Six of the 27 patients have been treated with this combination, and four of them remain free of disease from one and one-half to two and one-half years. These results suggest that early aggressive combined therapy consisting of radical surgery, postoperative radiation, and multidrug therapy can be expected to improve the survival rate. Surgery of Bladder and Prostatic Neoplasms Children H. William Clatworthy, Jr., M.D. Ohio State University College of Medicine
in
Rhabdomyosarcoma is a common malignant softtissue tumor in children, This tumor was found in the bladder or prostate in 12 of 67 patients recently treated at Children’s Hospital, Columbus, Ohio (6 are surviving). Until recently and regardless of the primary site, the reports of successful treatment of this aggressive embryonal neoplasm have been limited to a small series or to isolated cases treated by radical mutilative surgical procedures. Now, a combined therapy, which has proved effective in Wilms’ tumor, utilizing “reasonable surgical procedures” (excision of all
UROLOGY
/
MAY 1973
/
VOLUME
I, NUMBER 5