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Background: Surgical-pathological risk factors were evaluated by weighting the magnitude of significance of multiple risk factors correlating to survival and treatment response in cervical cancer., Methods: Multivariate analysis was performed for survival outcomes entering seven pathological factors obtained from 540 radical hysterectomy specimens in stage IA2-IIB cervical cancer cases. Hazard ratio (HR) in each risk factor was determined, and the sum of HR scores for the corresponding risk factors was determined per case. Survival curves and postoperative treatment response (concurrent chemoradiotherapy (CCRT) vs radiotherapy alone) were evaluated based on the extent of HR-weighted scores., Results: Hazard ratios for risk factors relating to disease-free survival (DFS) was: lympho-vascular space invasion 3.95, nodal metastasis 3.88, adenocarcinoma 3.40, large tumour 2.36, positive margin 1.99, deep stromal invasion 1.29, and parametria invasion 1.21. The HR-weighted scoring method showed a high predictive value for recurrence (area-under-curve 0.836, P<0.001). Hazard ratio-weighted scores were negatively correlated to DFS, and the cases with score 12.5 showed 5-year DFS rate of 23.8%. Tumours with larger score offset the benefits of CCRT over radiotherapy alone for postoperative adjuvant treatment (P<0.001)., Conclusion: Surgical-pathological risk factors provide valuable information for survival and management of early-stage cervical cancer when number and significance of risks are weighted.

Objective: To determine if the quantity of lymph vascular space invasion (LVSI) correlates with time to recurrence in women with early-stage squamous carcinoma of the cervix., Methods: 101 consecutive women with Stages IA2, IB, and IIA squamous carcinoma of the cervix who had undergone radical hysterectomy between 1991 and 1997, with previously reported histopathologic quantification of LVSI by four methods, were prospectively followed. The outcome measure was time to recurrence. Univariate and stratified log-rank test analysis was performed to test the association of time to recurrence with prognostic factors. Further analysis was focused on recurrence in those patients who had negative surgical margins and whose tumors contained LVSI, incorporating the four quantification measures., Results: Nineteen (19%) women had cancer recurrence. The presence of LVSI (P = 0.05), cervical stromal invasion (P = 0.01), parametrial involvement (P < 0.001), and positive margins (P < 0.0001) were significantly related to time to recurrence on univariate analysis. In patients whose tumors had negative surgical margins and contained LVSI (65%), percentage of all sections with LVSI >29% and total number of foci with LVSI >5 were significantly related to time to recurrence (P = 0.006). When stratifying for cervical stromal invasion, lymph node status, and parametrial involvement in this group, percentage of all sections with LVSI >29% and total number of foci with LVSI >5 were significantly related to time to recurrence (P = 0.05)., Conclusion: The quantity of LVSI, as defined by the percentage of all sections with LVSI and total number of foci with LVSI, is an independent prognostic factor for time to recurrence in women with early-stage squamous carcinoma of the cervix.

A 51-year-old man with type IV skin presented for evaluation of a generalized rash associated with multiple ulcerated, nodular lesions on his legs. The nodular lesions occurred approximately 18 months after the initial onset of generalized rash, which had been diagnosed as plaque/patch stage mycosis fungoides. He continued to develop further nodular lesions on his trunk in the weeks following presentation. The nodular lesions were shown to be squamous-cell carcinoma on histopathology. He had received only topical hydrocortisone prior to the development of the second cutaneous malignancy and had no past exposure to carcinogens. His squamous cell carcinomas were treated with surgical excision and split-skin grafting. He received total skin electron-beam therapy to treat the mycosis fungoides. Second malignancy in mycosis fungoides is a recognized phenomenon and usually occurs after potentially carcinogenic therapy. This case demonstrates the occurrence of second malignancy in the absence of a precipitating factor, suggesting that there are innate, immune-mediated mechanisms in the development of cancer in patients with mycosis fungoides.

Objective: The aim of this study was to determine the response rate and toxicity of cis-platinum and gemcitabine in advanced, recurrent, or persistent squamous cell carcinoma of the cervix., Methods: From July 1997 to January 1999, we conducted a Phase II trial in patients with advanced, persistent, or recurrent carcinoma of the cervix. The schedule employed 1250 mg/m(2) of gemcitabine on days 1 and 8 and 50 mg/m(2) of cis-platinum on day 1 in a 21-day cycle. Eligibility criteria were a GOG performance status of 0-2, adequate bone marrow reserve, serum creatinine less than 1.8 mg%, and a lesion which could be measured in two dimensions. None of the patients had received prior chemotherapy other than radiation sensitizers. Standard GOG toxicity and response criteria were used., Results: Nineteen patients were enrolled into the trial. Two patients were inevaluable because of inadequate trial of drug. Seventeen patients were evaluable for response and toxicity. The median age of the patients was 47 years (range 24-72). The median number of cycles delivered was 5 (range 2-8). The incidence of grade 4 neutropenia and anemia was 2.4 and 1.2%, respectively. Two patients developed a single episode of grade 3 gastrointestinal toxicity. The overall response rate was 41% (7/17). There was 1 complete response of 14 months duration and 6 partial responses. Among those patients not previously irradiated, the response rate was 57% (4/7). Among the radiated patients, the response rate was 30% (3/10) with all responses occurring in the radiation field., Conclusion: This combination of cis-platinum and gemcitabine is a well-tolerated regimen which exhibits high activity in advanced, recurrent, or persistent squamous cell cervical cancer., (Copyright 2000 Academic Press.)

Objective: To determine if the quantity of lymph-vascular space invasion influences the risk of pelvic nodal metastases in women with early-stage cervical squamous carcinoma., Methods: Between 1991 and 1997, 105 women with stages IA2, Ib, and IIa squamous carcinoma of the cervix underwent radical hysterectomy and pelvic lymphadenectomy. The histopathology slides were prospectively reviewed. If lymph-vascular space invasion (LVSI) was present, the amount was quantified in four ways: percentage of cervical histopathologic sections containing LVSI, percentage of sections with tumor containing LVSI, total number of foci of LVSI, and maximal number of foci of LVSI in 10 high-powered fields. These measures of LVSI were correlated with the risk of nodal metastases., Results: Seventy-three (70%) women had tumors with LVSI. Of these, 23 had pelvic nodal metastases. All women with nodal metastases had tumors with LVSI. Using logistic regession, independent predictors of nodal metastases were depth of cervical stromal invasion (P = 0.01) and tumor size (P = 0.04). LVSI was also a significant predictor of nodal metastases based on the Mantel-Haenszel test (P = 0.01). In women whose tumors contained LVSI, logistic regression identified tumor size (P = 0.004) and LVSI in > 45% of all cervical histopathologic sections (P = 0.002) as significant predictors of nodal metastases., Conclusion: The quantity of LVSI, as defined by the percentage of all cervical histopathologic sections containing LVSI, correlates significantly with the risk of nodal metastases in women with early-stage squamous carcinoma of the cervix.

Objective: To quantify the risk of residual invasion when cervical conization reveals microinvasive squamous carcinoma and to determine whether any factors affect this risk., Methods: We reviewed the charts and histopathology slides of 87 women who underwent a conization that contained microinvasive squamous carcinoma, followed by either a repeat conization or hysterectomy. Depth of invasion, number of invasive foci, and status of the internal margin and post-conization endocervical curettage (ECC) were assessed. The findings were correlated with the presence of residual invasion., Results: Significant predictors of residual invasion included status of the internal margin (residual invasion present in 22% of women with an involved margin versus 3% with a negative margin; P < .03) and the combined status of the internal margin and post-conization ECC (residual invasion in 4% of patients if both negative, 13% if one positive, and 33% if both positive; P < .015). Depth of invasion and number of invasive foci in the conization specimen were not significant. The power of this study to detect a 25% difference in the risk of residual invasion was 73% for depth of invasion and 75% for number of invasive foci., Conclusion: Women with microinvasive squamous carcinoma in a conization specimen in which both the internal conization margin and post-conization ECC are negative have a low risk of residual invasion and are candidates for follow-up or simple hysterectomy. If either the internal margin or the post-conization ECC contains dysplasia or carcinoma, the risk of residual invasion is high and warrants repeat conization before definitive treatment planning.

Objective: To report our experience with invasive carcinoma of the cervix during pregnancy, assessing maternal morbidity due to treatment delay and reporting maternal and fetal outcome., Methods: Twenty-seven patients with invasive cervical cancer, who were pregnant at the time of diagnosis or treatment, were identified from review of morbidity and mortality statistics between January 1, 1980 and December 31, 1991. All medical records were examined retrospectively., Results: The incidence of cervical carcinoma in our population was 1.2 cases per 10,000 pregnancies. Most patients had stage I lesions. The predominant histologic cell type was squamous cell carcinoma, followed by adenosquamous carcinoma and adenocarcinoma. Eight patients with stage Ia or Ib cervical cancer postponed therapy to optimize fetal outcome, with a mean diagnosis-to-treatment interval of 144 days (range 53-212). Nineteen patients elected immediate treatment, with a mean diagnosis-to-treatment interval of 17 days (range 2-42). Fetal outcome was uniformly good for the delayed-treatment group. Nine fetal deaths and two neonatal deaths occurred in the immediate-treatment group. All patients who delayed therapy are free of disease after a median follow-up of 23 months., Conclusion: Deliberate delay of therapy to achieve fetal maturity appears to be a reasonable option for patients with stage I cervical cancer complicating pregnancy.

Between June 20, 1977 and February 5, 1983, the Gynecologic Oncology Group entered 1180 women with clinical stage I or II (occult) endometrial carcinoma into a surgical-pathological staging study. Eight hundred ninety-five patients with endometrioid or adenosquamous carcinoma were evaluable for this study which relates surgical-pathological parameters and postoperative treatment to recurrence-free interval and recurrence site. Proportional hazards modeling of time to recurrence was performed. For patients without metastasis determined by surgical-pathological staging the greatest determinant of recurrence was grade 3 histology adenocarcinoma grade 3, relative risk (RR) = 15; adenosquamous carcinoma grade 3, RR = 8.1; all adenocanthomas, RR = 1.0). Of 48 patients with histologically documented aortic node metastases, 47 had one or more of the following features: (1) grossly positive pelvic nodes, (2) grossly positive adnexal metastasis, or (3) outer one-third myometrial invasion. Pelvic radiation was administered to 48.0% and vaginal brachytherapy alone to 10.2% of patients postoperatively; 41.8% received no adjuvant radiation therapy. None of three recurrences in the vaginal implant group were vaginal or pelvic; 7.4% (7 of 95) of recurrences in the pelvic radiation therapy (RT) group were vaginal and 16.8% were pelvic; 18.2% (8 of 44) of recurrences in the no adjuvant radiation group were vaginal and 31.8% pelvic. Because of the high degree of selection bias no valid comparisons can be made of recurrence-free interval in these groups. The 5-year recurrence-free interval for patients with negative surgical-pathological risk factors (other than grade and myoinvasion) was 92.7%; involvement of the isthmus/cervix 69.8%; positive pelvic cytology 56.0%; vascular space invasion 55.0%; pelvic node or adnexal metastases 57.8%; and aortic node metastases or gross laparotomy findings 41.2%. It is not clear that cervix invasion per se diminishes survival, because it is more often associated with poor tumor differentiation (34.7% versus 24.0%, grade 3) and deep myoinvasion (47.0 vs 18.6%) than cases without cervix invasion. The relapse rate among cervix-positive and -negative cases with grade 3 lesions and deep myoinvasion is not dramatically different (48.8% vs 39.8%). The proportion of failures which were vaginal/pelvic (34.6% for the surgery only group compared to 12.5% of the RT group) appears to favor the use of adjuvant radiation for patients with more than one-third myoinvasion and grade 2 or 3 tumor. There were 97 patients in the study group with malignant cytology of which 29.1% had regional/distant failure, which compares to 10.5% of the cytology-negative patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Serial carcinoembryonic antigen (CEA) assays were performed on 10 patients with primary invasive squamous cell carcinoma of the cervix, 7 patients with recurrent squamous cell carcinoma of the cervix, and 5 patients with invasive squamous carcinoma of the vulva. Plasma CEA determinations were accomplished by radioimmunoassay, using a modification of Hanson's method. In 8 of the 10 patients with invasive squamous cell carcinoma of the cervix, positive CEA values dropped to normal ranges during the course of radiotherapy, usually in the first 4 weeks of treatment. A similar decrease in patients' serum values was seen after surgical extirpation of recurrent squamous cell carcinoma of the cervix by pelvic exenteration. Serum values also dropped to within normal limits in a limited number of patients with squamous cell carcinoma of the vulva after complete removal of all gross disease. Persistence of disease was associated with all gross disease. Persistence of disease was associated with chronically elevated values. A suggestion is made that patients with elevated CEA values may be followed with serial determinations to substantiate complete eradication of their disease.

Results were evaluated for 651 consecutive patients with invasive cancer of the intact uterine cervix. From 1963 through 1967 319 patients were treated primarily with the older Los Angeles County Hospital system of orthovoltage radiation and intracavitary radium therapy. Thereafter, 1968--1974, 332 patients were treated primarily with a newer modified M. D. Anderson Tumor Institute system of megavoltage radiation and afterloading intracavitary radium therapy. Age distribution and histology were similar for both groups, but clinical stage was slightly more advanced for patients treated earlier. Crude and net 5 year survival rates were 36% and 49% for the early group and 54% and 67% for the later group. Net 5 year survival rates for the earlier group by stage were: stage I, 74%; II, 62%; III, 23%; and IV, 6%. Survival rates for the later group were: I, 81%; II 76%; III, 50%; and IV, 15%. We believe this improvement can be attributed to more effective intracavitary radium therapy for handling local cancer and to delivery of cancericidal doses of radiation to regional nodes with the megavoltage radiation apparatus, as well as to the greater cooperative efforts put forth in the management of County Hospital patients.

This study reviewed 20 cases of extensive squamous carcinoma in situ of the vulva and posterior perineum. Two patients had concurrent, overt invasive carcinoma of the vulva, 14 patients had concurrent extensive vulvar carcinoma in situ, three patients had previous skinning vulvectomy for carcinoma in situ, and one patient had prior treatment for invasive vulvar cancer. Six patients had microinvasive carcinoma in the perianal region, which was unsuspected in five of the women. Nineteen of the 20 patients had involvement of the anal canal, and eight patients had disease extending to, or above, the pectinate line. Nineteen patients were managed by regional resection of the involved perianal/anal skin and mucosa with split thickness skin graft. Routine resection of the anal mucosa to the pectinate line was performed, with margin checks when there was dysplasia in the anal canal. The only noteworthy, long-term adverse effect of resecting the anal mucosa and replacing it with a split thickness skin graft was occasional incontinence of flatus in three of the 19 patients. The skinning procedure with split thickness skin graft produced excellent functional and cosmetic results.

Single-agent chemotherapy of advanced and recurrent squamous carcinoma of the female genital tract has been largely ineffective. Combination-drug therapy which has augmented the efficacy of chemotherapy in numerous solid and nonsolid human tumors is usually attended by a degree of toxicity that has discouraged its use against malignancies exhibiting a poor response to single agents. A seven-drug regimen consisting of cyclophosphamide, 5-fluorouracil, actinomycin D, vincristine, cytosine arabinoside, methotrexate, and bleomycin administered during a 24 hour period at 4 week intervals was selected for clinical trial against squamous malignancies of the female genitalia because of its proved broad-spectrum activity among solid tumors and its low incidence of serious toxicity. Severe bone marrow depression occurred during only two of 98 drug cycles involving 23 patients. An objective tumor response was observed in nine of 18 evaluable patients. This regimen appears to be useful in the palliative management of squamous carcinoma of the female genital tract.

Ninety-six patients with cervical cancer underwent surgical staging prior to radiation therapy. An equal number of patients were explored by transperitoneal and extraperitoneal surgery. Three different extraperitoneal approaches were utilized. All patients had bilateral paraaortic lymphadenectomy and selective pelvic nodal sampling. Intraperitoneal cytology and selected biopsies were performed. A 52% correlation existed between clinical and surgical staging. Radiotherapeutic treatment decisions were subsequently based on findings at operative staging. Nine percent of patients undergoing transperitoneal staging experienced a small bowel injury after radiation requiring surgical correction. No patients undergoing extraperitoneal surgery experienced postradiation small bowel morbidity. Extended field radiation was administered to 17% of patients, and a 30% five-year disease-free survival rate was observed. Although prognostic stratification is enhanced with surgical staging, using current radiotherapy techniques, the majority of patients with paraaortic nodal metastases will fail treatment. Based on our experience, only 2.5% of patients in a Stage IIB-IVA category will benefit from radiotherapeutic treatment decisions made as a consequence of staging laparotomy.