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Prognostic value of scalene node biopsy in cervical cancer
268
SOCIETY OF GYNECOLOGIC
ONCOLOGISTS-ABSTRACTS
grossly examined, and the depth of invasion was estimated as either less than 50% or greater than or equal to 50% of the myometrium. With grade 1 and grade 2 lesions, pelvic and paraaortic lymph nodes were sampled in only those patients estimated to have 50% or greater myometrial invasion. All patients with a grade 3 lesion had nodal sampling regardless of the depth of invasion. This technique is one method to identify certain patients with Stage I endometrial adenocarcinoma who should have a sampling of the pelvic and paraaortic lymph nodes. 54. Radical Hysterectomy and Pelvic Lymphadenectomy for Stage IB Carcinoma of the Cervix: 21 Years Experience. L. ARTMAN, W. HOSKINS, M. BIBRO, P. HELLER, E. WEISER, D. BARNHILL, AND R. PARK, Division of Gynecologic Oncology, Uniformed Services University of the Health
Sciences, Bethesda, Maryland 20814. From September 1971through December 1982, 156 patients with Stage IB carcinoma of the cervix underwent radical hysterectomy and pelvic lymphadenectomy at two of the teaching hospitals of the Uniformed Services University of the Health Sciences. Records were retrospectively analyzed and independent pathologic review was performed. In this series IB carcinoma was defined as squamous carcinoma confined to the cervix with invasion greater than 5 mm from the basement membrane or any adenocarcinoma confined to the cervix. The average age was 38.3 years. The histologic types were squamous 71%. adenocarcinoma 16.5%, and adenosquamous 10%. The mean operating time was 5 hr 40 min with an average blood loss of 1800 ml. There were 2 ureterovaginal and 2 vesicovaginal tistulae for an overall rate of 2.6%. Actuarial survival for these 156 patients is 84.3%. Although the survival for patients with pure squamous lesions was 90% during the period of study, the actuarial survival for patients with an adenomatous component from 1972through 1982 was only 62%. Additionally these patients constituted 50% of those dying of disease. This extends the previous series of Park et al. (1973) of 126 cases collected from 1961 to 1971 to 282 cases. In comparing the two IO-year periods, no significant differences were found in operative technique or complications, but there was a change in the incidence of adenocarcinoma and mixed cell types and in survival. A relatively higher incidence of more aggressive tumors may indicate the need for different therapeutic approaches in the future. 55. Treatment of a Syngeneic Rat Tumor with Magnetically Responsive Albumin Microspheres Labeled with Adriamycin or Protein A. M. RETTENMAIER, J. STRATTON, P. DISAIA, M. BERMAN, A. SENYEI, AND K. WIDDER, University of California, Irvine, Department of OB/GYN, Division
of GYN/Oncology,
Orange, California 92668.
The tumoricidal activity of magnetically responsive albumin microspheres (MRAM) tagged with either Adriamycin or Protein A was tested against an induced mammary adenocarcinoma, 13762, implanted subcutaneously in the tail of female Fischer-344 rats. MRAM containing Fe 304 particles were prepared by an emulsion polymerization method and tagged with either doxyrubicin or Protein A. Microspheres with an average diameter of 1 pm were produced in a concentration of 10’ microspheres per milligram. A single bolus of microspheres was injected either directly into the tail artery and localized to the implanted tumor, using a permanent bipolar adjustable gap magnet with a field strength of 8000 Oe; or directly into the femoral vein without magnetic localization. Three separate control groups consisted of animals treated with (1) intravenously or (2) intraarterially administered blank microspheres, and (3) a no-treatment group. Survival in bott.’ the Adriamycin- and Protein Atreated animals was significantly greater than in the three control groups (P < 0.05). Animals treated with intraarterial localized Adriamycin MRAM had significantly prolonged time to progression when compared to all other groups (P < 0.05). Tumor growth rate was significantly depressed in all intraarterial magnetically localized groups (Adriamycin, Protein A, and blank) when compared to intravenously administered nonlocalized groups (P < 0.05). Magnetically responsive albumin microspheres appear to be an effective delivery system for cytotoxic agents and biologic response modifiers. Significant tumoricidal activity was seen when MRAM labeled with doxyrubicin or Protein A were magnetically localized to a syngeneic rat adenocarcinoma. 56. Prognostic Value of Scalene Node Biopsy in Cervical Cancer. J. AXELROD, R. FRUCHTER, AND J. BOYCE, Downstate Medical Center, Brooklyn, New York 11203.
SOCIETY OF GYNECOLOGIC
ONCOLOGISTS-ABSTRACTS
269
This study concerns itself with the practical importance of metastasis to the scalene node in the length of survival and development of distant metastasis. Sixty-two patients (pts) had scalene node biopsies (SNB). Ten nodes were positive (pas) and 52 were negative (neg). Patients were divided into six groups (Gp)-Gp 1: neg SNB, no paraaortic node biopsy (PNB) (18 pts); Gp 2: neg SNB followed by pos PNB (12 pts); Gp 3: neg SNB followed by pos PNB (6 pts): Gp 4: neg PNB followed by neg SNB (II pts); Gp 5: pos PAN followed by neg SNB (5 pts): Gp 6: pos SNB (IO pts). Mean survival for neg nodes was 20-22.3 months, while for pos nodes (SNB or PNB) was 6-14 months. Distant metastases were seen in all categories except Gp 2: however they were in greater frequency in those pts with pos PNB or pos SNB (Gp 3,5, and 6-3/6, 2/S, and 3/10. respectively) compared to those with neg nodes (Gp I, 2, and 4-3/18. 2/12, and O/l I. respectively). The data suggest that although pts with pos PNB have a poorer survival than pts with neg PNB, pos SNB does not cause a further decline in survival. Also, since distant metastases are as frequent in pts with pos PNB/neg SNB as those with pos SNB, patients with pos PNB/neg SNB should be considered as candidates for systemic chemotherapy. Lymph Node Germinal Centers curd Metctstutic Cuncer. C. B. Bovo AND M. ASHRAF, Department of Pathology and the Gynecologic Oncology Section of Department of Obstetrics and Gynecology, West Virginia University Medical Center, Morgantown, West Virginia 26506-
57. Paruaortic
6302
The observation that germinal centers within paraaortic lymph nodes examined at frozen section could be predictive of metastatic cancer within the nodes was tested by reviewing the tissue removed from 124 women having lymphadenectomies during surgical evaluation or treatment of gynecologic cancer. Sixty-nine cases of cervical cancer with acceptable lymph node tissue revealed a 98%~ predictive value that the absence of germinal centers meant the absence of metastatic cancer in that node. Thirty percent of lymph nodes containing germinal centers harbored metastatic carcinoma (7 of 24 cases). Forty-nine cases of endometrial cancer with lymph nodes examined intraoperatively gave a 100% predictive value for germinal center negative nodes. None of 35 such nodes had metastatic cancer. Four of I4 nodes with germinal centers (28.5%) had metastases. A fifth case was predicted and found on permanent sections. The observation concerning paraaortic germinal centers will be valuable during the intraoperative evaluation of the patient with gynecologic cancer. 58. A Preliminrrry fntruperitoneul
Report on the Toxicity and Phrrnnucokinetics of Comhinrrtion Systemic, clnd Chemotherapy in Adwnced Epitlzeliul Ovtrricrn Cuwer-. G. DEPPE, V. MALVIYA.
D. DECKER, L. EVANS, J. YOUNG. AND B. Oncology, Detroit. Michigan 48201
SCHILCHER,
Wayne State University. Division Gyni
In order to determine the pharmacokinetics and extent of toxicity with combination systemic and intraperitoneal chemotherapy, 5 previously untreated patients wtih advanced ovarian cancer received intraperitoneal doxorubicin and intravenous cyclophosphamide and cisplatin following maximum debulking surgery. lntraperitoneal doxorubicin was administered in escalating doses (20-40 mg) in 2 liters of dialysate as a 4-hr, 2-liter dwell, via Tenckhoff catheter on Day I, every 3 weeks. Cisplatin. 50 mg/m’, and cyclophosphamide, 500 mg/m’, were given intravenously on Day 2 every 3 weeks. Dosages were escalated until the first evidence of toxicity was noted. Patients who were clinically free of disease following this regimen underwent a laparoscopy after 4 courses and a second-look laparotomy after 8 courses of chemotherapy. The dose-limiting toxicity of doxorubicin was chemical peritonitis with severe abdominal pain. No patient was able to tolerate more than 40 mg of intraperitoneal doxorubicin. Other toxicities observed were systemic myelosuppression, obstructed catheter. catheter exit site infection, abdominal discomfort, vomiting, and alopecia. Adriamycin concentrations in plasma and peritoneal fluid were measured by high-performance liquid chromatography (HPLC) using fluorescence detection. Of the administered dose, 4-20s was recovered in the peritoneal fluid after 4 hr. The peak plasma concentration of 54 ? 33 rig/ml of Adriamycin occurred within I hr after intraperitoneal instillation of the dialysate and decreased to 4.2 2 I .9 g/ml by 24 hr. The preliminary data reported here supports further investigation of the delivery of intraperitoneal chemotherapy in combination with systemic chemotherapy in patients with advanced ovarian cancer.
SOCIETY OF GYNECOLOGIC
ONCOLOGISTS-ABSTRACTS
grossly examined, and the depth of invasion was estimated as either less than 50% or greater than or equal to 50% of the myometrium. With grade 1 and grade 2 lesions, pelvic and paraaortic lymph nodes were sampled in only those patients estimated to have 50% or greater myometrial invasion. All patients with a grade 3 lesion had nodal sampling regardless of the depth of invasion. This technique is one method to identify certain patients with Stage I endometrial adenocarcinoma who should have a sampling of the pelvic and paraaortic lymph nodes. 54. Radical Hysterectomy and Pelvic Lymphadenectomy for Stage IB Carcinoma of the Cervix: 21 Years Experience. L. ARTMAN, W. HOSKINS, M. BIBRO, P. HELLER, E. WEISER, D. BARNHILL, AND R. PARK, Division of Gynecologic Oncology, Uniformed Services University of the Health
Sciences, Bethesda, Maryland 20814. From September 1971through December 1982, 156 patients with Stage IB carcinoma of the cervix underwent radical hysterectomy and pelvic lymphadenectomy at two of the teaching hospitals of the Uniformed Services University of the Health Sciences. Records were retrospectively analyzed and independent pathologic review was performed. In this series IB carcinoma was defined as squamous carcinoma confined to the cervix with invasion greater than 5 mm from the basement membrane or any adenocarcinoma confined to the cervix. The average age was 38.3 years. The histologic types were squamous 71%. adenocarcinoma 16.5%, and adenosquamous 10%. The mean operating time was 5 hr 40 min with an average blood loss of 1800 ml. There were 2 ureterovaginal and 2 vesicovaginal tistulae for an overall rate of 2.6%. Actuarial survival for these 156 patients is 84.3%. Although the survival for patients with pure squamous lesions was 90% during the period of study, the actuarial survival for patients with an adenomatous component from 1972through 1982 was only 62%. Additionally these patients constituted 50% of those dying of disease. This extends the previous series of Park et al. (1973) of 126 cases collected from 1961 to 1971 to 282 cases. In comparing the two IO-year periods, no significant differences were found in operative technique or complications, but there was a change in the incidence of adenocarcinoma and mixed cell types and in survival. A relatively higher incidence of more aggressive tumors may indicate the need for different therapeutic approaches in the future. 55. Treatment of a Syngeneic Rat Tumor with Magnetically Responsive Albumin Microspheres Labeled with Adriamycin or Protein A. M. RETTENMAIER, J. STRATTON, P. DISAIA, M. BERMAN, A. SENYEI, AND K. WIDDER, University of California, Irvine, Department of OB/GYN, Division
of GYN/Oncology,
Orange, California 92668.
The tumoricidal activity of magnetically responsive albumin microspheres (MRAM) tagged with either Adriamycin or Protein A was tested against an induced mammary adenocarcinoma, 13762, implanted subcutaneously in the tail of female Fischer-344 rats. MRAM containing Fe 304 particles were prepared by an emulsion polymerization method and tagged with either doxyrubicin or Protein A. Microspheres with an average diameter of 1 pm were produced in a concentration of 10’ microspheres per milligram. A single bolus of microspheres was injected either directly into the tail artery and localized to the implanted tumor, using a permanent bipolar adjustable gap magnet with a field strength of 8000 Oe; or directly into the femoral vein without magnetic localization. Three separate control groups consisted of animals treated with (1) intravenously or (2) intraarterially administered blank microspheres, and (3) a no-treatment group. Survival in bott.’ the Adriamycin- and Protein Atreated animals was significantly greater than in the three control groups (P < 0.05). Animals treated with intraarterial localized Adriamycin MRAM had significantly prolonged time to progression when compared to all other groups (P < 0.05). Tumor growth rate was significantly depressed in all intraarterial magnetically localized groups (Adriamycin, Protein A, and blank) when compared to intravenously administered nonlocalized groups (P < 0.05). Magnetically responsive albumin microspheres appear to be an effective delivery system for cytotoxic agents and biologic response modifiers. Significant tumoricidal activity was seen when MRAM labeled with doxyrubicin or Protein A were magnetically localized to a syngeneic rat adenocarcinoma. 56. Prognostic Value of Scalene Node Biopsy in Cervical Cancer. J. AXELROD, R. FRUCHTER, AND J. BOYCE, Downstate Medical Center, Brooklyn, New York 11203.
SOCIETY OF GYNECOLOGIC
ONCOLOGISTS-ABSTRACTS
269
This study concerns itself with the practical importance of metastasis to the scalene node in the length of survival and development of distant metastasis. Sixty-two patients (pts) had scalene node biopsies (SNB). Ten nodes were positive (pas) and 52 were negative (neg). Patients were divided into six groups (Gp)-Gp 1: neg SNB, no paraaortic node biopsy (PNB) (18 pts); Gp 2: neg SNB followed by pos PNB (12 pts); Gp 3: neg SNB followed by pos PNB (6 pts): Gp 4: neg PNB followed by neg SNB (II pts); Gp 5: pos PAN followed by neg SNB (5 pts): Gp 6: pos SNB (IO pts). Mean survival for neg nodes was 20-22.3 months, while for pos nodes (SNB or PNB) was 6-14 months. Distant metastases were seen in all categories except Gp 2: however they were in greater frequency in those pts with pos PNB or pos SNB (Gp 3,5, and 6-3/6, 2/S, and 3/10. respectively) compared to those with neg nodes (Gp I, 2, and 4-3/18. 2/12, and O/l I. respectively). The data suggest that although pts with pos PNB have a poorer survival than pts with neg PNB, pos SNB does not cause a further decline in survival. Also, since distant metastases are as frequent in pts with pos PNB/neg SNB as those with pos SNB, patients with pos PNB/neg SNB should be considered as candidates for systemic chemotherapy. Lymph Node Germinal Centers curd Metctstutic Cuncer. C. B. Bovo AND M. ASHRAF, Department of Pathology and the Gynecologic Oncology Section of Department of Obstetrics and Gynecology, West Virginia University Medical Center, Morgantown, West Virginia 26506-
57. Paruaortic
6302
The observation that germinal centers within paraaortic lymph nodes examined at frozen section could be predictive of metastatic cancer within the nodes was tested by reviewing the tissue removed from 124 women having lymphadenectomies during surgical evaluation or treatment of gynecologic cancer. Sixty-nine cases of cervical cancer with acceptable lymph node tissue revealed a 98%~ predictive value that the absence of germinal centers meant the absence of metastatic cancer in that node. Thirty percent of lymph nodes containing germinal centers harbored metastatic carcinoma (7 of 24 cases). Forty-nine cases of endometrial cancer with lymph nodes examined intraoperatively gave a 100% predictive value for germinal center negative nodes. None of 35 such nodes had metastatic cancer. Four of I4 nodes with germinal centers (28.5%) had metastases. A fifth case was predicted and found on permanent sections. The observation concerning paraaortic germinal centers will be valuable during the intraoperative evaluation of the patient with gynecologic cancer. 58. A Preliminrrry fntruperitoneul
Report on the Toxicity and Phrrnnucokinetics of Comhinrrtion Systemic, clnd Chemotherapy in Adwnced Epitlzeliul Ovtrricrn Cuwer-. G. DEPPE, V. MALVIYA.
D. DECKER, L. EVANS, J. YOUNG. AND B. Oncology, Detroit. Michigan 48201
SCHILCHER,
Wayne State University. Division Gyni
In order to determine the pharmacokinetics and extent of toxicity with combination systemic and intraperitoneal chemotherapy, 5 previously untreated patients wtih advanced ovarian cancer received intraperitoneal doxorubicin and intravenous cyclophosphamide and cisplatin following maximum debulking surgery. lntraperitoneal doxorubicin was administered in escalating doses (20-40 mg) in 2 liters of dialysate as a 4-hr, 2-liter dwell, via Tenckhoff catheter on Day I, every 3 weeks. Cisplatin. 50 mg/m’, and cyclophosphamide, 500 mg/m’, were given intravenously on Day 2 every 3 weeks. Dosages were escalated until the first evidence of toxicity was noted. Patients who were clinically free of disease following this regimen underwent a laparoscopy after 4 courses and a second-look laparotomy after 8 courses of chemotherapy. The dose-limiting toxicity of doxorubicin was chemical peritonitis with severe abdominal pain. No patient was able to tolerate more than 40 mg of intraperitoneal doxorubicin. Other toxicities observed were systemic myelosuppression, obstructed catheter. catheter exit site infection, abdominal discomfort, vomiting, and alopecia. Adriamycin concentrations in plasma and peritoneal fluid were measured by high-performance liquid chromatography (HPLC) using fluorescence detection. Of the administered dose, 4-20s was recovered in the peritoneal fluid after 4 hr. The peak plasma concentration of 54 ? 33 rig/ml of Adriamycin occurred within I hr after intraperitoneal instillation of the dialysate and decreased to 4.2 2 I .9 g/ml by 24 hr. The preliminary data reported here supports further investigation of the delivery of intraperitoneal chemotherapy in combination with systemic chemotherapy in patients with advanced ovarian cancer.