Charles W. Whitney

Randomized Comparison of Fluorouracil Plus Cisplatin Versus Hydroxyurea as an Adjunct to Radiation Therapy in Stage IIB-IVA Carcinoma of the Cervix With Negative Para-Aortic Lymph Nodes: A Gynecologic Oncology Group and Southwest Oncology Group Study

PURPOSE In 1986, a protocol comparing primary radiation therapy (RT) plus hydroxyurea (HU) to irradiation plus fluorouracil (5-FU) and cisplatin (CF) was activated by the Gynecologic Oncology Group (GOG) for the treatment of patients with locally advanced cervical carcinoma. The goals were to determine the superior chemoradiation regimen and to quantitate the relative toxicities. METHODS All patients had biopsy-proven invasive squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix. Patients underwent standard clinical staging studies and their tumors were found to be International Federation of Gynaecology and Obstetrics stages IIB, III, or IVA. Negative cytologic washings and para-aortic lymph nodes were required for entry. Patients were randomized to receive either standard whole pelvic RT with concurrent 5-FU infusion and bolus CF or the same RT plus oral HU. RESULTS Of 388 randomized patients, 368 were eligible; 177 were randomized to CF and 191 to HU. Adverse effects were predominantly hematologic or gastrointestinal in both regimens. Severe or life-threatening leukopenia was more common in the HU group (24%) than in the CF group (4%). The difference in progression-free survival (PFS) was statistically significant in favor of the CF group (P = .033). The sites of progression in the two treatment groups were not substantially different. Survival was significantly better for the patients randomized to CF (P = .018). CONCLUSION This study demonstrates that for patients with locally advanced carcinoma of the cervix, the combination of 5-FU and CF with RT offers patients better PFS and overall survival than HU, and with manageable toxicity.

Reducing Uncertainties About the Effects of Chemoradiotherapy for Cervical Cancer : A Systematic Review and Meta-Analysis of Individual Patient Data From 18 Randomized Trials

BACKGROUND After a 1999 National Cancer Institute (NCI) clinical alert was issued, chemoradiotherapy has become widely used in treating women with cervical cancer. Two subsequent systematic reviews found that interpretation of the benefits was complicated, and some important clinical questions were unanswered. PATIENTS AND METHODS We initiated a meta-analysis seeking updated individual patient data from all randomized trials to assess the effect of chemoradiotherapy on all outcomes. We prespecified analyses to investigate whether the effect of chemoradiotherapy differed by trial or patient characteristics. RESULTS On the basis of 13 trials that compared chemoradiotherapy versus the same radiotherapy, there was a 6% improvement in 5-year survival with chemoradiotherapy (hazard ratio [HR] = 0.81, P < .001). A larger survival benefit was seen for the two trials in which chemotherapy was administered after chemoradiotherapy. There was a significant survival benefit for both the group of trials that used platinum-based (HR = 0.83, P = .017) and non-platinum-based (HR = 0.77, P = .009) chemoradiotherapy, but no evidence of a difference in the size of the benefit by radiotherapy or chemotherapy dose or scheduling was seen. Chemoradiotherapy also reduced local and distant recurrence and progression and improved disease-free survival. There was a suggestion of a difference in the size of the survival benefit with tumor stage, but not across other patient subgroups. Acute hematologic and GI toxicity was increased with chemoradiotherapy, but data were too sparse for an analysis of late toxicity. CONCLUSION These results endorse the recommendations of the NCI alert, but also demonstrate their applicability to all women and a benefit of non-platinum-based chemoradiotherapy. Furthermore, although these results suggest an additional benefit from adjuvant chemotherapy, this requires testing in randomized trials.

Positive groin lymph nodes in superficial squamous cell vulvar cancer: A gynecologic oncology group study

The term microinvasive carcinoma is inappropriate when applied to all vulvar cancers less than or equal to 5 mm thick because approximately 50% of vulvar carcinomas are no thicker than 5 mm and 20% of those superficial tumors metastasize to the lymph nodes. The significant predictors of groin node metastases in patients with superficial vulvar cancer are tumor thickness, histologic grade (proportion of undifferentiated tumor pattern), capillary-like space involvement with the tumor, clitoral or perineal location, and clinically suspicious nodes, according to the linear logistic model analysis of clinicopathologic data in 272 women. No lymph node metastases occurred in approximately one fourth of patients with a combination of low-risk factors: no clinically suspicious nodes, negative capillary-like space, and nonmidline vulvar cancers that were either grade 1 and 1 to 5 mm thick or grade 2 and 1 to 2 mm thick. In contrast, all 10 patients with clinically suspicious nodes and grade 4 tumors had positive groin nodes. The risk of lymph node metastases is best determined by simultaneous evaluation of all risk factors rather than a single factor such as tumor thickness.

CA 125 serum levels correlated with second-look operations among ovarian cancer patients

CA 125, which is an antigenic determinant expressed by many epithelial ovarian cancers, is measured in serum using a solid phase immunoradiometric assay. Sera from 55 patients who were in clinical remission and underwent a second-look operation to assess disease status after chemotherapy were studied prospectively. All patients had the CA 125 assay performed within one week before their second-look operation. Twenty-four patients (44%) had no histologic or cytologic evidence of disease, seven patients (13%) had microscopic disease, 13 patients (24%) had disease measuring 1 mm to 1.5 cm, and ten patients (18%) had disease greater than or equal to 1.5 cm in maximum tumor dimension. None of the 24 patients with a negative second-look operation had a positive CA 125 antigen level (greater than or equal to 35 U/mL), compared with six of 20 patients (30%) with less than 1.5 cm disease, and six of ten (60%) with greater than or equal to 1.5 cm disease (P less than .0001). All 12 patients with an elevated CA 125 antigen level (greater than or equal to 35 U/mL) had disease discovered at their second-look operation. Thus, in this setting the predictive value of a positive CA 125 titer (greater than or equal to 35 U/mL) was 100%. The predictive value of a negative CA 125 antigen level (less than 35 U/mL) was 56%, ie, the test did not exclude the presence of disease in 44% of patients with a positive second look. The maximum tumor size associated with at least one prior negative antigen level was 1.9 cm.(ABSTRACT TRUNCATED AT 250 WORDS)

Surgical versus radiographic determination of para-aortic lymph node metastases before chemoradiation for locally advanced cervical carcinoma: a Gynecologic Oncology Group Study.

Patients with cervical cancer who had negative para‐aortic lymph nodes (PALNs) identified by pretreatment surgical staging were compared with patients who had only radiographic exclusion of PALN metastases before they received treatment with pelvic radiation and brachytherapy (RT) plus cisplatin (C)‐based chemotherapy.

The CA 125 assay as a predictor of clinical recurrence in epithelial ovarian cancer

Abstract Serum CA 125 levels were obtained from 55 women with epithelial ovarian cancer before a second-look surgical procedure and serially thereafter. All patients were clinically and radiographically free of tumor at the time of the second-look operation and were followed to clinical recurrence. Median follow-up was 12 months. CA 125 levels obtained at the second-look operation had a sensitivity and specificity for predicting clinical recurrence of 94% and 88%, respectively. Patients with an elevated CA 125 level (≥35 U/ml) had a 60% chance of clinical recurrence within 4 months, while patients with levels

Second-Look Laparotomy in Ovarian Cancer

Abstract Between July 1970 and February 1980, 160 patients were treated for malignant epithelial ovarian cancers. Twenty-seven patients underwent second-look laparotomy for evaluation of chemotherapeutic or radiation therapy effect. These patients were clinically free of disease at the time of exploratory laparotomy. Ten had persistent disease discovered at the time of second-look laparotomy while seventeen had no evidence of cancer. Fourteen of those patients with no evidence of cancer at second-look remain free of disease. Three have recurred. This study indicates that second-look laparotomy is an appropriate step in the proper care of certain patients with epithelial ovarian cancer.

Synchronous carcinomas of the uterine corpus and ovary

The coexistence of carcinoma in the endometrium and ovary is a relatively uncommon but not rare occurrence. In general it has not been possible to determine which, if any, of these tumors represent metastases from endometrium or ovary or separate primary neoplasms, and gynecologists are unable to agree upon appropriate therapy. Twenty-four women with synchronous carcinomas of the ovary and endometrium in whom disease was confined to the pelvis, diagnosed at the Milton S. Hershey Medical Center between 1970 and 1982, were identified. Thirteen women had typical endometrial adenocarcinoma and endometrioid carcinoma of the ovary (Group A), two had unusual variants of endometrial carcinoma and a similar appearing tumor in the ovary (Group B), and nine had typical endometrial adenocarcinoma with carcinomas in the ovary of differing histologic appearance (Group C). There was no significant difference in survival between women in Groups A and C (77 and 56%, respectively, mean follow-up approximately 40 months). However, deep myometrial invasion (outer third) provided a statistically significant indicator of poor prognosis (77% with deep invasion vs 17% with superficial invasion recurred or died of disease P less than 0.05, chi 2 test).

The preservation of ovarian function in young women undergoing pelvic radiation therapy

Because cervical carcinoma rarely metastasizes to the ovaries, it became logical to preserve ovarian function by the method of lateral ovarian transposition as part of the management of young women with this disease. This technique prevents castration should subsequent radiation therapy be planned or become necessary. Forty patients with carcinoma of the cervix or vagina underwent unilateral or bilateral ovarian transposition. Eighteen patients received radiation therapy. Of these, 16 had gonadotropin measurements and only 6 (37%) had levels elevated to the postmenopausal range. If patients whose ovaries were not shielded or who received paraaortic radiotherapy are excluded, then only two (17%) had elevated gonadotropin values. It is concluded that, if properly performed, lateral ovarian transposition and ovarian shielding will protect ovarian function in patients receiving pelvic radiotherapy.

Bowel obstruction in patients with ovarian carcinoma: Analysis of prognostic factors

A retrospective study was performed in which patients with both bowel obstruction and ovarian carcinoma admitted to the gynecologic oncology service at the Milton S. Hershey Medical Center between July 1, 1980, and June 30, 1987, were examined. Thirty-three patients were identified who fulfilled the inclusion criteria for bowel obstruction that did not occur in the postoperative period. Historical, physical, nutritional, and laboratory variables thought to contribute to patient survival were evaluated by a retrospective chart review. Survival time was not significantly related to presence or absence of tumor at obstruction, type of intervention whether medical or surgical, patient age, or interval from initial diagnosis of ovarian cancer to obstruction. Survival time was found to be significantly related to the prognostic index initially proposed by H. B. Krebs and D. R. Goplerud [Obstet. Gynecol. 61, 327-330 (1983)], P = 0.002. This prognostic index incorporates a multifactorial assessment of patient status including age, nutritional status, tumor spread, ascites, and prior chemotherapy and radiotherapy and can be used to evaluate patients at the time of presentation with intestinal obstruction and to help select optimal treatment for palliation.