Fine-needle aspiration cytology in the management of gynecologic neoplasms

SOCIETY OF GYNECOLOGIC management of GTD patients requires a multidiscipline approach that in many cases can best be achieved at specialized treatment centers. 18. Concomitant

Whole Abdominal Radiation and Intraperitoneal Cisplatin Chemotherapy in Advanced Ovarian Carcinoma: A Pilot Study. L. KING, L. ADCOCK, G. DOWNEY, R. POTISH, G. OAKLEY, L. CARSON, K. PREM, AND L. Twmos, University of Minnesota

Women’s Cancer Center, Minneapolis, Minnesota 55455. As the use of cisplatin-based chemotherapy for ovarian carcinoma has not significantly improved S-year survival as compared to either whole abdominal radiation (WAR) or single agent chemotherapy, a pilot study to assess the feasibility of combined radiation and chemotherapy was undertaken. Eleven previously untreated patients with Stage III and IV ovarian carcinoma were entered in a pilot project using whole abdominal radiation (WAR), 2000 rad, and intraperitoneal (ip) cisplatin (toxicity was graded according to GOG criteria). Toxicity was moderate to severe; 64% of patients had Grade 3-4 hematologic toxicity and 36% of patients required hospitalization for sepsis. All patients experienced moderate gastrointestinal toxicity. Weight loss was significant during treatment, with the average percentage of total body weight loss being 13.5%. Of nine evaluable patients, 67% demonstrated an initial response to therapy. At present, with follow-up of 8-16 months, 33% are clinically free of disease, with the remainder having recurrence of, progression of, or death from disease. In conclusion, toxicity appears to be additive with the combined use of WAR and ip cisplatin. Initial response rate to therapy was good but further assessment of therapeutic efficacy needs additional follow-up and study. Significance of the Tumor Marker Squamous-Cell Carcinoma Antigen in Diagnosis and Follow-up of Cervical Cancer. G. CROMBACH, H. W~~RZ, F. HERRMANN, R. KREIENBERG,V. M~BUS, P. SCHMIDT-RHODE, G. STURM, H. CAFFIER, H. KAESEMANN, AND P. G. KNAPSTEIN, University of Mainz, West Germany.

19. Clinical

SCC (squamous-cell carcinoma) antigen is a subfraction of tumor antigen TA-4 isolated from cervical squamous-cell carcinomas. Serum concentrations of SCC antigen were measured by radioimmunoassay in 382 control subjects, 70 women with cervical intraepithelial neoplasia (GIN), 517 with cervical carcinoma, and 203 with other gynecological carcinomas. Elevated SCC antigen levels (2.5 rig/ml) were found in 4% of normal controls, in 7% of women with CIN I-III, in 2-23% with various forms of genital adenocarcinomas, in 55% with primary cervical SCC, and in 76% of those with recurrent cervical squamouscell carcinoma. The positivity rate of the antigen was correlated with tumor stage (FIGO) and lymph node involvement of primary cervical squamous-cell carcinomas. During long-term follow-up serum levels of SCC antigen were found to be concordant with tumor activity in 74% of cases. Patients with still elevated marker levels after therapy had twice the recurrence rate of women with normal serum values. Routine determination of SCC antigen during follow-up of cervical cancer is recommended. 20. Patterns of Care Studies in III-B Cervix Cancer: Tumor and Treatment Factors Improving Outcome. R. LANCIANO, K. MARTZ, L. COIA, AND G. HANKS, Fox Chase Cancer Center, Philadelphia,

Pennsylvania 19111. This report reviews 271 patients with Stage III-B squamous cell cancer of the uterine cervix from three national surveys. One survey was conducted in five large facilities to establish outcome with “optimal” radiation therapy (RT). The other two surveys were designed to establish the national average for RT in 1973 and 1978. There was a progressive increase in local control from 45 to 67% (P < 0.01) and survival from 33 to 51% (P = 0.03) as seen among the three surveys.

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ONCOLOGISTS-ABSTRACTS

Patterns of treatment among the three surveys demonstrated a progressive increase in median point A dose (P < 0.01) and use of intracavitary radiation (ic) (P < 0.01) which parallels the improved LC and S. Multivariate analysis revealed bulk of disease (unilateral sidewall vs bilateral sidewall vs lower one-third vagina) to be the most significant tumor factor with respect to LC (P < 0.01) and S (P < 0.001). Multivariate analysis showed the use of ic was the most significant treatment factor with respect to LC (P < 0.001) and S (P < 0.001). There has been an improvement in the national average from 1973 to 1978 which has not yet reached the success of the large facilities. New treatment strategies for Stage III-B cervix cancer must include ic with high point A dose and should stratify based on tumor bulk. Survey (4 year)

1973 large facility 1978 natural average 1973 national average

sew

LC(%)

Point A dose

ic(%)

51 40 33

67 50 45

8476 8042 7375

85 79 65

21. Experience with the Endo-Pap Device for the Cytological

Detection of Uterine Cancer and Its Precursors: A Comparison of the EndoPap Sampler with Fractional Curettage/Hysterectomy. J. LAPOLLA, S. NICOSIA, C. SONGSTER,P. TOWNSEND, W. ROBERTS, M. HOFFMAN, J. FIORICA, E. RUFFOLO, AND D. CAVANAGH, University

of South Florida, Tampa, Florida 33612. The value of the Endo-Pap endometrial cell sampler in the cytological assessment of the endometrium was compared with fractional curettage or hysterectomy in 250 symptomatic women (67 corpus cancer, 32 endometrial hyperplasia, 12 ovarian/fallopian tube cancer, 23 cervical cancer, 116 benign disease). Satisfactory material for the diagnosis of the endometrial state was obtained in 98%. Fifty-nine of 66 women with primary cancer of the uterine corpus had atypical or worse endometrial cytology (sensitivity 0.89). The causes for a false negative result were sampling error (3) and cancer within a small residual (< 1 cm) focus or polyp (4). The sensitivity for the detection of hyperplasia with Endo-Pap sampling was 0.65 (20/31). Of the 11 patients with a false negative cytology, 8 had mild or focal cystic hyperplasia. For 6 patients with atypical adenomatous hyperplasia, the sensitivity was 1.00. Eleven patients with ovarian or fallopian tube carcinoma had normal endometrial histology and in 5 (Four-Stage IC or greater, OneStage IA) abnormal uterine cytology was present. Ninety-six percent of uterine cervical cancers were detected by Endo-Pap cytologic sampling. The specificity of the cytologic diagnosis of benign conditions was 0.74. The Endo-Pap endometrial sampler is an inexpensive device for outpatient cytological assessment of the endometrium. The method has a reasonably high sensitivity to detect uterine cancers and preinvasive endometrial lesions with a high risk of progression to carcinoma. 22. Fine-Needle Aspiration Cytology in the Management of Gynecologic Neoplasms. L. J. LAYFIELD, J. M. HEAPS, AND J. S. BEREK,

UCLA School of Medicine, Los Angeles, California 90024. Between 1984and 1988,62 fine-needle aspirations (FNA) of palpable lesions were obtained from 59 gynecologic-oncology patients seen at the UCLA Medical Center. Sites of aspiration included abdomen, cervix, vagina, superficial lymph nodes, and pelvic masses. Confirmatory open biopsy (41 aspirates) or adequate clinical follow-up (17 aspirates) was obtained in 55 patients (58 aspirates). In the biopsied cases, FNA correctly established the diagnosis of malignancy in 19 of 26 cases resulting in a predictive value for a positive test of 100% and a predictive value for a negative test of 82%. Initial surgical biopsy had been incorrectly benign in 4 of these cases which were shown to be malignant by FNA and subsequent clinical findings. In 7 cases, FNA failed to diagnose the malignancy revealed by open biopsy. Two of

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SOCIETY OF GYNECOLOGIC

ONCOLOGISTS-ABSTRACTS

these falsely negative FNAs had been reported as insufficient while the remaining five were from poorly palpable surgical biopsy but with adequate clinical follow-up, FNA correctly predicted subsequent clinical course in 15 patients (88%). In this study, no false positive FNA results were correlated with FNA. Aspiration cytology was associated with a specificity of 100% and a diagnostic sensitivity of 65%. Negative FNAs obtained from clinically suspicious lesions should be followed by reaspiration or surgical biopsy.

were used; complications included infections in 3 pts, extravasation in 2 pts requiring catheter removal in 4 pts. Median follow-up for all pts is 17 months (l-39). Among pts receiving IPPC as primary therapy 62% are alive at 24 months and 2 (28.5%) are NED. Among those getting salvage therapy, 13% survive at 24 months and 2 (16%) are NED. Median PFI for the former group was 10 months (3-35). MST for the latter was 8.8 months (l-39). IPPC is well tolerated and possesses activity which warrants further trials.

23. A Longitudinal Study of the Distribution of Intraperitoneally Administered Fluids as Determined by Radionuclide Scanning. C. LEVENBACK, J. CURTIN, S. RUBIN, S. YEH, H. HOSKINS, D. CHAPMAN, W. JONES, T. HAKES, M. MAFXMAN, B. REICHMAN, AND J. L. LEWIS, JR., Memorial Sloan-Kettering Cancer Center, New York, New York 10021.

25. Intraperitoneal (ip) Mitoxantrone (M) in Refractory Ovarian Carcinoma (ROC). M. MARKMAN, M. GEORGE,T. HAKES, B. REICHMAN, W. HOSKINS, S. RUBIN, L. ALMADRONES, AND J. L. LEWIS, JR., Memorial Sloan-Kettering Cancer Center, New York, New York 10021.

Intraperitoneal (ip) chemotherapy holds promise for improved results in patients with ovarian cancer. Adhesions resulting from tumor, surgery, or the ip chemotherapy itself may limit distribution of ip fluids. We assessed changes in the distribution of ip-administered fluids over time using radionuclide scanning. Sixteen patients on prospective ip chemotherapy protocols had scans at least 4 weeks apart. Thirteen patients had three scans and three patients had two scans. Normal saline (500-1000 ml) with 99mTc-labeled human serum albumin was given through ip catheters and scanning performed. Scan results were reported as percentages of total activity per quadrant. “Normal” distribution was assumed to be 25% per quadrant. “Abnormal” was arbitrarily assigned as less than 16% per quadrant, a 40% decline. No correlation was found between scan findings and the following clinical features using multiple regression analysis: number of prior ovarian cancer laparotomies, amount of residual disease, and time interval between scans. No significant changes in mean activity per quadrant were observed over the course of the study. The total number of abnormal quadrants per scan was: scan 1, 13/64 (20%); scan 2, 13/64 (20%); scan 3, 17/52 (33%). The number of patients with at least one abnormal quadrant per scan was: scan 1, 9/16 (56%); scan 2, 9/16 (56%); and scan 3, 11/13 (85%). The changes in distribution of ip fluids observed during this preliminary analysis did not reach statistical significance. Changes in distribution over time and the relationship of distribution to the efficacy of ip therapy will be evaluated further as more patients are accrued. 24. Intraperitoneal Cisplatin Plus Intravenous Cyclophosphamide (ZPPC) in Ovarian Carcinoma. K. LOOK, G. SUTTON, F. STEHMAN, AND C. EHRLICH, Indiana University School of Medicine, Indianapolis, Indiana 46202. From July 1985 to September 1988, 19 patients (pts) with ovarian cancer received intravenous cyclophosphamide (750 mg/m* Day 1) and intraperitoneal cisplatin (200 mg/m’ Day 2) every 3 weeks. Sodium thiosulfate, 7.5 g/m” iv bolus followed by 2 g/m’/h infusion, was given with cisplatin as a nephroprotector. Seven pts received IPPC as primary therapy and 12 received it as salvage. All but 3 pts had FIG0 Stage III disease. One hundred two courses were given (median 6 per pt, range 1 to 8). The median cisplatin dose was 1885 mg (320-3200) and the median cyclophosphamide dose was 4875 mg (700-I 1,500). The median progression free interval (PFI) was 6.5 months (l-35) in the 8 pts with ascites and 11 months (3-39) in the 11 pts without ascites. In the 12 salvage pts the median PFI fell from 12 months in those with no ascites (N = 5) to 2 months in the 7 pts with ascites (<0.05). Ten pts were evaluable for control of ascites. In the pts with persistent ascites (N = 5) the median survival time (MST) was 6 months versus 23+ months in those with control of ascites (P < 0.05). GOG grade 3 to 4 hematologic toxicity occurred in 7 pts (36.8%); grade 1 or 2 renal toxicity occurred in 3 pts (15.7%); grade 1 neurotoxicity occurred in 2 pts (10.5%). Portacath (N = 13) and Tenckhoff (N = 6) catheters

To assess both the safety and clinical utility of ip M in ROC, 31 patients (pts) were treated with this agent monthly for 6 months. Pts without clinical evidence of disease at the completion of therapy underwent a laparotomy to assess response. The initial dose selected (30 mg/m’) resulted in unacceptable abdominal pain. At 20 mg/m’ pain was less severe but narcotic analgesia was still frequently required. Six pts experienced bowel obstruction either during or following the completion of therapy. Dense adhesion formation was noted at response laparatomy in most pts. Median follow-up from treatment initiation is 18+ months (range 12+ -26 + months). Eleven pts have died; 6 (5 CR)/18 (33%) pts whose largest tumor diameter was ~1 cm responded, compared to 1 (0 CR)/11 (9%) pts whose largest tumor diameter was >l cm. Two pts were not evaluable for response (1 removed for toxicity while NED; 1 refused surgical assessment). Three pts who had previously failed to respond to ip cisplatin responded to ip M. With a median follow-up from surgery of 13+ months (range 8 + -17 +) 2/5 pts in CR have relapsed (9 and 20 months from surgery). In conclusion, ip M results in surgically defined responses in pts with ROC. It is hoped that further modifications in this treatment regimen will result in less local toxicity while maintaining or improving therapeutic efficacy. 26. Phase 2 Trial of Intraperitoneal (ip) Cisplatin (C) and Ara-C (A) in Refractory Ovarian Carcinoma (ROC). M. MARKMAN, T. HAKES, B. REICHMAN, W. JONES, W. HOSKINS, S. RUBIN, L. ALMADRONES, E. L. YORDAN, JR., J. H. ERIKSSON,AND J. L. LEWIS, JR., Memorial Sloan-Kettering Cancer Center, New York, New York 10021and Rush-Presbyterian-St. Luke’s Medical Center, Chicago, Illinois 60612. Preclinical evaluation has suggested impressive synergy between C and A in ovarian carcinoma. To define the efficacy of this regimen in ROC, 39 pts were treated on a 2- or 3-day ip regimen of C-A repeated monthly x 5 courses. Pts in a clinical CR underwent a laparotomy to define response. The initial 3-day program (C 35 mg/m*/day, A 300 mg/day) resulted in excessive marrow suppression. With the 2-day regimen (C 50 mg/m*/day, A 300 mg/day) toxicity was acceptable but marrow suppression remained dose limiting. Additional toxicity has included mild to moderate abdominal pain and frequent fever (secondary to A). Ten pts are currently not evahrable for response (8 remain on therapy; 1 refused surgery; 1 removed for toxicity while NED); 11/29 (38%) evaluable pts have responded, including 10 (5 CR)/17 pts (59%) with no tumor nodule >l cm in diameter and only 1 (0 CR)/12 pts (8%) with any lesion >1 cm. Median follow-up from treatment initiation is 12+ months (range (3+-18+ months). In conclusion, ip C-A results in a high surgically defined response rate in pts with small volume ROC but demonstrates minimal activity in pts with any bulky intraabdominal disease. 27. Stage I-R Adenocarcinoma of the Cervix: Clinicopathologic Correlations. R. MCLELLAN, A. HALLUM, J. CURR~E,R. KUmAN,