Hugh M. Shingleton

Results and complications of operative staging in cervical cancer: Experience of the Gynecologic Oncology Group

Abstract A multiinstitutional study by the Gynecologic Oncology Group (GOG) has confirmed that clinical staging often is inaccurate in determining the extent of disease in patients with cervical cancer. The finding of positive paraaortic nodes in 29% of patients with Stage II, III, and IV tumors supports this conclusion. In this series, the incidence of paraaortic nodal metastases could not be correlated with the histologic grade of the tumors . With positive paraaortic nodes, conventional treatment limited to the pelvis can be expected to fail, but it is still not clear how many patients can be salvaged by treatment to extended paraaortic radiation fields . Longer periods of follow-up in patients whose treatment plans were based on surgical staging information will be required.

Cis‐platinum in treatment of advanced or recurrent squamous cell carcinoma of the cervix: A phase ii study of the gynecologic oncology group

Thirty‐four patients with advanced or recurrent squamous cell carcinoma of the cervix no longer amenable to control with surgery and/or radiotherapy were treated with cis‐platinum 50 mg/m2 intravenously every three weeks. Among 22 patients who had received no prior chemotherapy, three complete and eight partial responses were observed (response rate 50%), whereas only two partial responses were observed among 12 patients who had received prior chemotherapy (response rate 17%). The observed response rate was marginally significantly higher among those with no prior chemotherapy (P = 0.059). The overall frequency of response was 38% (13/34). Responses were observed in those with pelvic (7/20) as well as extrapelvic disease (6/14). Adverse effects included primarily leukopenia (11/34), thrombocytopenia (13/34), nausea and vomiting (29/34), and azotemia (17/34). Adverse effects were generally mild to moderate and hence tolerable. Cis‐platinum thus appears to be a highly active agent in the treatment of squamous cell carcinoma of the cervix at the dose and schedule tested.

Hydroxyurea or placebo combined with radiation to treat stages iiib and iv cervical cancer confined to the pelvis

Abstract In a prospective study by the Gynecologic Oncology Group (GOG), 104 evaluable patients with cervical squamous cell carcinoma Stages IIIB and IVA were randomly assigned to treatment with hydroxyurea or placebo in combination with radiation. There were no deaths resulting from the treatment. Hematologic toxicity was more common and more severe in patients who received hydroxyurea. Response was evaluated in terms of complete tumor regression, duration of progression-free interval and survival probability. By all those parameters the response was significantly better in the groups of patients receiving hydroxyurea.

Adenocarcinoma of the cervix: I. Clinical evaluation and pathologic features

A series of 137 patients with primary adenocarcinoma of the cervix is presented with emphasis on clinical and histologic features. Adenocarcinoma has several distinct histologic patterns that may occur in a pure form but often occur (44%) in combinations of two or more patterns. Mixtures of adenocarcinoma and squamous cell carcinoma occur in one third of the patients and squamous intraepithelial neoplasia occurs in one tenth. Transmission electron microscopy is helpful in classifying poorly differentiated tumors. Preliminary recurrence/survival data suggest that the identification of patterns and subpatterns has no prognostic significance, nor is there evidence that adenocarcinoma (or adenosquamous carcinoma) metastasizes earlier, metastasizes more frequently, or is more radioresistant. For most patients, treatment may be the same as that for squamous cell carcinoma but a few selected patients with bulky central lesions may benefit from combined therapy consisting of whole-pelvis irradiation and conservative hysterectomy.

Identification of prognostic factors and risk groups in patients found to have nodal metastasis at the time of radical hysterectomy for early-stage squamous carcinoma of the cervix☆

In a retrospective study conducted at the University of Alabama at Birmingham, the University of Michigan, and the Mayo Clinic, 185 patients with previously untreated FIGO stage IB and IIA squamous cell carcinoma of the cervix were found to have nodal metastasis at the time of radical hysterectomy and pelvic lymphadenectomy. Of these patients, 103 received adjuvant pelvic irradiation. Cancer recurred in 76 patients; the median time to recurrence was 3.1 years. The prognostic significance of patient age, clinical stage, lesion diameter, number and location of nodal metastases, and use of adjuvant radiation therapy was determined by multivariate analysis. Only patient age (P = 0.0006), lesion diameter (P less than 0.0001), and number of nodal metastases (P = 0.0004) were noted to be significant factors in determining overall survival. Rates of recurrence were also related to these factors. Employment of these significant variables led to identification of four risk groups. In general, patients with small cervical lesions (diameter less than 1 cm) and no more than two nodes with metastases fell into the low-risk category; those patients with large cervical lesions (diameter greater than 4 cm) and more than two involved nodes fell into the high-risk category. All other patients were categorized into intermediate-risk groups. Ten-year survival was 92% in the low-risk group (n = 13), 70% in the low-intermediate-risk group (n = 66), 56% in the high-intermediate-risk group (n = 66), and 13% in the high-risk group (n = 20). This risk group classification identifies subgroups of early-stage cervical carcinoma patients found to have nodal metastasis at the time of radical hysterectomy that warrant appropriately selected adjuvant therapy.

Value of adjuvant whole-pelvis irradiation after Wertheim hysterectomy for early-stage squamous carcinoma of the cervix with pelvic nodal metastasis: A matched-control study☆

In a retrospective study, 185 patients with previously untreated stage IB or IIA (International Federation of Gynecology and Obstetrics) squamous cell carcinoma of the cervix were found to have pelvic nodal metastasis at the time of Wertheim hysterectomy and bilateral pelvic lymphadenectomy. Of these patients, 103 received adjuvant whole-pelvis irradiation and 82 received no adjuvant therapy. Median dose of pelvic irradiation was 5000 cGy. Among the irradiated patients, in 75% the dose was 5000 cGy or greater. Matching irradiated and nonirradiated patients according to stage, tumor size, and number and location of positive nodes yielded 60 pairs. Mean length of follow-up was 3.9 years for the 60 irradiated patients and 5.8 years for the non-irradiated patients. Kaplan-Meier overall and cancer-specific survival estimates for the two groups were not significantly different (P greater than 0.30). During the follow-up period, 21 surgery-only patients and 22 patients treated with adjuvant radiotherapy had recurrence, but adjuvant radiotherapy decreased the proportion of recurrences occurring in the pelvis alone--27% compared with 67% in the surgery-only group (P = 0.01).

Complications of combined radical hysterectomy—Postoperative radiation therapy in women with early stage cervical cancer

Fifty patients with cervical cancer were treated with radical hysterectomy and lymphadenectomy followed by postoperative radiation therapy for high risk factors (nodal metastases, lymphvascular space invasion, close or involved margins) at the University of Alabama at Birmingham Medical Center from 1969 to 1984. Fifteen (30%) of the patients treated had serious complications, 8 (16%) requiring an operation, and 1 (2%) dying as a result of treatment-related problems. This combined modality approach is associated with significant complications.

Clinical and histopathologic factors predicting recurrence and survival after pelvic exenteration for cancer of the cervix

&NA; Between September 1969 and January 1, 1986, 143 pelvic exenterations for recurrent cervical cancer were performed by the gynecologic oncologists at the University of Alabama at Birmingham. Of this group, 78 patients underwent total pelvic exenteration, 63 patients had anterior exenteration, and two had posterior exenteration. The overall operative mortality rate was 6.3%, mostly associated with total pelvic exenteration. The 5‐year survival rates were 50% overall, 63% with anterior exenteration and 42% with total exenteration. Univariate and multivariate analyses were performed to identify clinical and histopathologic factors predictive of prolonged survival. Using three clinical factors (duration from initial radiation therapy to exenteration, size of the central mass, and presence of preoperative sidewall fixation), low‐, intermediate‐, and high‐risk groups were constructed; the 5‐year survival rates for these groups were 82, 46, and 0%, respectively. Inclusion of one histopathologic factor (margin status of the surgical specimen) added to the ability to predict 2‐ and 5‐year survival rates. The best candidates for cure by pelvic exenteration were those with recurrent small (less than 3 cm), mobile central masses who were a year or longer from the time of their previous radiation therapy. Attempts to resect bulky pelvic recurrences that impinge on the pelvic sidewall, especially in the case of persistent or early recurrent disease (within 6 months), or continuation of exenterative procedures in women known to have nodal metastases or extrapelvic spread, are generally futile. For those women falling between the two extremes, sound clinical and operative judgment is imperative in regard to selecting the treatment offering the best quality of life. (Obstet Gynecol 73:1027, 1989)

Primary Surgical Therapy of Ovarian Cancer: How Much and When

From July 1975 through December 1985, 328 patients with ovarian malignancies were treated. Of these, 302 had epithelial invasive malignancies and constitute the study group. The impact of the operative procedure, findings, and subsequent treatment is evaluated. Patients who underwent extensive debulking procedures such as bowel resection and peritoneal stripping did not have improved survival compared with those patients who did not undergo these procedures and yet had residual disease remaining (P = 0.7 and P = 0.34). Reoperating patients felt to be unresectable at the time of referral did not increase survival over reoperating patients after an attempt at chemotherapeutic reduction (P = 0.34).

c-myc amplification in ovarian cancer

The c-myc oncogene codes for a DNA binding protein that appears to play an important role in the regulation of cell growth. c-myc gene amplification has been documented to occur in both hematopoietic and solid neoplasms and often indicates more biologically aggressive tumors. Southern hybridization analysis was performed on high-molecular-weight DNA isolated from primary ovarian carcinomas. Major structural rearrangements of c-myc were not detected. Five of seventeen (29.4%) tumor samples demonstrated amplification of the myc oncogene. The 5 patients with ovarian carcinomas associated with c-myc amplification exhibited a median survival of 17 months. Of the 12 patients without evidence of tumor-associated c-myc amplification, 5 have exhibited disease-free survival for an average of 36.8 months and are currently alive. The remaining 7 patients, the majority of whom had advanced-stage, poorly differentiated lesions with a normal c-myc copy number, exhibited a median survival of 9 months. There was no apparent relationship between c-myc amplification, grade of tumor differentiation, and response to platinol-based chemotherapy. These data do not suggest a prognostic role for c-myc amplification in primary ovarian cancer. However, c-myc amplification is a common finding in advanced-stage ovarian cancer.