Extranodal Rosai-Dorfman disease as a pelvic mass.

Rosai-Dorfman disease (RDD) is a rare histiocytic disorder of unknown cause. RDD most commonly involves the cervical lymph nodes, but extranodal involvement has been described. We report the case of a patient with extranodal RDD that presented as a retroperitoneal mass obstructing the left ureter. The patient underwent surgical resection of the mass, followed by a 5-month course of vinblastine. There was no evidence of progressive disease 22 months after surgery.

Progression-free interval in ovarian cancer and predictive value of an ex vivo chemoresponse assay.

The study objective was to determine the effectiveness of a phenotypic chemoresponse assay in predicting response to chemotherapy measured by progression-free interval (PFI) in a retrospective series of ovarian cancer patients whose tumor specimens had been tested with the ChemoFx assay. A statistically significant correlation between assay prediction of response and PFI was observed in 256 cases with an exact or partial match between drug(s) assayed and received. In 135 cases with an exact match, the hazard ratio for progression of the resistant group was 2.9 (confidence interval [CI]: 1.4-6.3; P < 0.01) compared to the sensitive group and 1.7 (CI: 1.2-2.5) for the intermediate compared to the sensitive group. The median PFI for patients treated with drugs assayed as resistant was 9 months, 14 months for those with drugs assayed as intermediately sensitive, and PFI had not been achieved for those with drugs assayed as sensitive. These data indicate that the ChemoFx assay is predictive of PFI in ovarian cancer. As the majority of ovarian cancers display different degrees of response to different chemotherapy agents ex vivo, the incorporation of assay information into treatment selection has the potential to improve clinical outcomes in ovarian cancer patients.

Benign metastasizing leiomyoma responsive to megestrol: case report and review of the literature.

Benign metastasizing leiomyoma (BML) is an unusual condition typically treated by surgical resection and hormonal therapy. A 37-year-old woman presented with dyspnea 6 years after uterine myomectomy. Computed tomographic scans showed pelvic and right-sided lung masses. Total abdominal hysterectomy and right salpingo-oophorectomy revealed only leiomyomas and benign ovarian cysts. Thoracotomy revealed multiple nodules consistent with leiomyomas. Estrogen and progesterone receptors on lung and uterine tissue were positive. A 21- x 18-mm residual area of neoplasm in the lung completely resolved 3 months after treatment with megestrol. The patient remains free of disease 3 years after lung resection. We present a rare case of BML in which the lung neoplasm responded to megestrol alone in the setting of intact ovarian function.

Predictive value of the ATP chemosensitivity assay in epithelial ovarian cancer.

OBJECTIVE: The aims of this study were to define the specific parameters of the ATP chemosensitivity assay which most accurately predict a patient's clinical response to chemotherapeutic agents in epithelial ovarian cancer and to assess the clinical utility of the ATP assay. METHODS: In our laboratory from 1992 to 1994, fresh tumor specimens from patients with epithelial ovarian carcinomas were assayed with the ATP chemosensitivity assay (ATP-CSA) for their in vitro responses to several chemotherapeutic agents including cisplatin, paclitaxel, and cyclophosphamide. Clinical data on 161 of those patients including all follow-up assessments were then collected, and an investigator blinded to the in vitro assay results determined the patients' responses to chemotherapy. In order to determine which parameter of the assay was the best predictor of clinical response for each drug, receiver-operator characteristic (ROC) curves were constructed for several parameters, including the amount of cell kill at particular dosage levels of drug, the slope of the dose-response curve, and the IC50, or the average concentration of drug at which 50% of the cells were nonviable. RESULTS: The specific parameter of the ATP-CSA which was most predictive of clinical response differed for each drug tested. The resulting positive predictive values for cisplatin, cyclophosphamide, and paclitaxel ranged from 70.0 to 78.3% and negative predictive values from 46.2 to 60.9%, with overall ATP-CSA positive and negative predictive values of 83.0 and 56.5%. Overall, patients whose tumors tested sensitive to an agent in vitro were almost twice as likely (83% versus 43%) to show a clinical response (RR 1.91, 95% CI 1.34-2.71). CONCLUSION: Analysis of the ROC curves in this study shows that different parameters of the ATP-CSA need to be utilized for each drug tested in order to give the best prediction of clinical chemosensitivity. Although the ATP-CSA shows predictive ability, routine use of the ATP-CSA for clinical selection of drug therapy in patients with epithelial ovarian cancer would not be warranted without a prospective study comparing chemotherapy treatment based on assay results versus clinician selection of drug.

Pelvic exenteration.

Pelvic exenterations are the most extensive surgeries performed for patients with gynecologic cancer, and the surgical team and patients have to be fully aware of the many issues that come into the discussion. This article discusses the history, indications, surgical techniques, and complications of pelvic exenteration.

[Survival tree analysis--a new method for multivariate evaluation of prognostic factors in operative cervix carcinoma]. / "Survival Tree Analysis"-eine neue Methode zur multivariaten Bewertung von Prognosefaktoren beim operablen Zervixkarzinom.

OBJECTIVE: We introduce a new multivariate analysis, not yet applied to gynecologic cancer, that includes the creation of a survival tree. The tree structured survival analysis is a statistical method designed to identify meaningful prognostic subsets in a study population, which usually do not emerge from routine proportional hazards analysis. We also applied the scoring systems from other groups to our patients and compared them with our system using a variety of statistical methods. MATERIAL AND METHODS: After excluding patients with microinvasive and small cell carcinoma, data from remaining 301 patients were analyzed. We performed an univariate and multivariate analysis. Significant single parameters and other variables considered important were chosen for multivariate analysis, including the creation of a survival tree. RESULTS: Risk factors to define prognosis best were: Depth of invasion, lymph vascular space involvement, age of 40 years and lymph node metastases. CONCLUSIONS: The presented model separates patients with early stage invasive carcinoma of the cervix into three subgroups with a significant different survival and correlates well with other models. Our new model is easy to apply and only requires depth of invasion, lymph vascular space involvement, node status and age of a patient to define the individual risk.

Limb sparing surgery for vulvar groin recurrence: a case report and review of the literature.

Hemipelvectomy was successfully avoided in a patient with extensive necrotic groin recurrence of vulvar cancer after prior radiation therapy. Tumor-free resection margins were achieved by wide excision of the recurrence including resection of the pubic bone and adjacent muscles. After resection of the femoral artery, blood supply to the leg was restored by an extra-anatomic axillopopliteal bypass. A myocutaneous flap from the contralateral rectus abdominis was used for primary wound closure. Limb salvage was achieved and the patient experienced pain relief, excellent cosmesis, and independent gait. Aspects of treatment options, even though primarily palliative, in groin recurrence of vulvar carcinoma are discussed.

Social implications of sexually transmitted cancer.

The long, tedious search for the causes of and cure for the human nemesis, cancer, has not resulted in one astounding breakthrough discovery. Instead, researchers have slowly and painstakingly made small inroads into the understanding of the way cell growth goes awry and becomes malignant, destroying tissues and, if unchecked, spreading to other organs of the body and eventually causing death. One of those inroads is the discovery that a cancer of the uterine cervix is almost certainly caused by a virus transmitted through sexual contact. This article presents the biological, clinical, and psychosocial aspects of cervical cancer. Cancer of the cervix usually is preceded by a slowly progressive preinvasive lesion, dysplasia, which can be detected by a screening test, the Papanicolaou smear, and effectively treated with organ-preserving local therapy. Because dysplasia and early invasive cancer usually develop in young women, the need for conservative management is of utmost importance to preserve a woman's ability to have children. The social and psychological impacts of a cancer occurring in young women are enormous and are further magnified by the fact that this cancer may be caused by a sexually transmitted virus. Sexual practice patterns, number of sexual partners, smoking, and other behavioral aspects contribute to the complexity of this disease. However, early detection of preinvasive and invasive cancer is possible with fairly simple and inexpensive means, and curative therapy is available. The disastrous impact of cervical cancer theoretically could be contained if patients at risk regularly participate in early detection programs. Also, the disease could, to a large extent, be prevented altogether through healthful behavior and sexual practices. The social challenge is to provide this information to the public in a nonthreatening, nonmoralistic fashion. We especially need to help young people to accept that sex within a caring, responsible relationship is a healthy human response and, at the same time, understand that there are dangers associated with transmittable diseases that can have profound effects on their ability to have children and on their lives.

Management of microinvasive cervical cancers.

The management of microinvasive carcinoma of the cervix (MIC) has been ill-defined in the past and is a persistent focus of controversy. MIC with

In vitro sensitivity of fresh ovarian carcinoma specimens to CPT-11 (irinotecan).

OBJECTIVE: Irinotecan (CPT-11) is a DNA topoisomerase I inhibitor which has shown activity in vitro against several cancer cell lines and some promising clinical responses in phase I and II trials in various solid tumors. The cytotoxicity of CPT-11 on human ovarian epithelial malignancies was tested in vitro utilizing the ATP chemosensitivity assay. Flow cytometry was also performed on the fresh carcinoma specimens. METHODS: Fresh tumor samples were obtained at laparotomy from 20 patients with primary adenocarcinoma of the ovary and 1 patient with heavily pretreated recurrent ovarian carcinoma. Tumors were plated in an in vitro system and treated with varying doses of both CPT-11 and its active metabolite SN-38 (7-ethyl-10-hydroxycamptothecin), in addition to a panel of standard chemotherapeutic agents used in treating ovarian cancer. On the sixth day after incubation, ATP levels in remaining cells were measured using a luminometer as an indication of the amount of cell kill compared to untreated controls. RESULTS: Twelve of the 21 tumors were evaluable for a response to CPT-11. Of the 12 tumors tested, 7 were found to have median effect doses of CPT-11 significantly under the clinically achievable peak plasma concentration (range 1.00 x 10(-4) to 44.67 microM) and 11 of the 12 tumors showed sensitivity to the active metabolite SN38 with median effect doses ranging from 2.00 x 10(-4) to 0.147 microM. Some of these tumors showed resistance to the standard agents, such as platinum, based on our assay. The heavily pretreated recurrent tumor tested was very sensitive to both CPT-11 and SN38 by our assay. The results of flow cytometry showed that the tumors were composed of heterogeneous populations of cells with mean S phase fractions varying from 7.0 to 17.3%. The only tumor not sensitive to SN38 showed the highest mean S phase activity of 17.3%. CONCLUSIONS: Overall, these results suggest that CPT-11 deserves further investigation as a clinically useful chemotherapeutic agent for ovarian cancer.

Amonafide in patients with leiomyosarcoma of the uterus: a phase II Gynecologic Oncology Group study.

Twenty-six evaluable patients who had leiomyosarcoma of the uterus were treated with amonafide, 300 mg/m2, for 5 consecutive days every 3 weeks. One partial response (4%) resulted. Hematologic toxicity was substantial, with grade 3 or 4 events occurring as follows: leukopenia, 12 patients (46%); thrombocytopenia, 4 patients (15%); and granulocytopenia, 7 patients (27%). One patient had transient grade 4 renal failure. Considering the poor activity and substantial toxicity that was observed, no further studies are planned by the Gynecologic Oncology Group using amonafide at this dose schedule in leiomyosarcomas.

p53 interference and growth inhibition in p53-mutant and overexpressing endometrial cancer cell lines.

BACKGROUND: The presence of p53 mutations and associated mutant p53 overexpression has been demonstrated in many cancer systems. Whether the overexpression of mutant p53 represents cause or effect, and whether p53 mutation contributes actively to the malignant phenotype is a matter of controversy. We examined the growth effects of oligonucleotides designed to interfere with p53 expression and/or activity in p53-mutant/overexpressing endometrial cancer cell lines. METHODS: Phosphorothioate oligonucleotides were used to target p53-related sequences in two p53-mutant/overexpressing endometrial cancer cell lines (KLE and RL95-2) and a normal fibroblast control. The ATP cell viability assay was used to measure growth effects after 6-day treatments with 27-mer and 14-mer sense (S) or antisense (AS) phosphorothioate oligodeoxyribonucleotides (oligos) targeting the promoter/ATG region of p53 and/or the p53 consensus (CON) DNA binding sequence. These sequences were designed to interfere with p53 expression and activity, respectively. Random sequences of the p53 27- and 14-mer were used as controls for nonspecific oligo effects, and a normal fibroblast cell line was used to compare oligo effects and serve as a negative p53 immunostaining control. RESULTS: Mean +/- SE IC50 (50% growth inhibition) of the S, AS p53, and p53 CON oligos were 4.2 +/- 1.3, 4.7 +/- 0.9, and 7.6 +/- 1.4 microM, respectively, for the two endometrial cell lines combined. The AS and S p53 oligos demonstrated dose-dependent inhibitory effects in both cell lines, while p53 CON produced variable effects alone and in combination with p53 AS. In KLE, a uniform inhibitory dose response was seen with p53 CON oligos. In RL95-2, the approximate IC50 for p53 CON was 0.5-1.0 microM, but at increasing doses above this, an inverse dose response was consistently observed. Combinations of p53 AS and p53 CON oligos produced predominantly synergistic growth inhibition. Although combinations of p53 AS and p53 CON in KLE were synergistic at low doses, antagonistic effects occurred at higher concentrations. Oligos had little effect on normal fibroblast growth, with calculated IC50 > 16 microM. Equimolar combinations of p53 S and AS were antagonistic, indicating that antiproliferative effects were sequence-specific. Random oligos demonstrated some nonspecific inhibitory effects, with >25% growth inhibition at 16 microM and beyond. Immunoperoxidase staining for mutant p53 after exposure to 16 microM concentrations of p53 AS oligos demonstrated reductions in p53 staining but persistent overexpression relative to wild-type (fibroblast) cells. CONCLUSION: Phosphorothioate oligos directed against p53 sequences in two p53-mutant endometrial cancer cell lines demonstrated antiproliferative effects. Combined anti-p53 and anti-p53 binding site oligos resulted in predominantly synergistic antiproliferative effects. The activity of sense oligos, the variable responses to p53 CON, and the persistent overexpression of mutant p53 at high concentrations of growth-inhibiting anti-p53 oligos suggest that, while promising, the antineoplastic effects of these oligos occur through complex and incompletely understood mechanisms.

Tumor heterogeneity and in vitro chemosensitivity testing in ovarian cancer.

OBJECTIVE: Our purpose was to study the heterogeneity of drug response in fresh human ovarian tumors to chemotherapeutic agents in an in vitro chemosensitivity assay. STUDY DESIGN: This assay evaluates total tumor cell kill by measuring the intracellular adenosine triphosphate levels of untreated controls and drug-exposed cells at various doses after culture for 6 days. The surviving fraction is calculated by dividing the treated values with the control values. One hundred tumors were tested against four single drugs (cisplatin, the active metabolite of cytoxan, 4-hydroxyperoxy-cyclophosphamide, Taxol, and carboplatin) and two drug combinations (cisplatin plus 4-hydroxyperoxy-cyclophosphamide; cisplatin plus Taxol). RESULTS: There is great variation in the degree of cell death for single drugs and drug combinations among the 100 tumors tested. CONCLUSION: More effective clinical response to chemotherapy may be achieved in patients with ovarian cancer by selecting the most active drugs for chemotherapy, on the basis of in vitro chemosensitivity test results for individual patients.

Radiosensitivity patterns of four human ovarian cancer cell lines in vitro.

Clinical evidence and the majority of experimental data suggest a cross-resistance between cisplatin and radiation in ovarian cancer. The authors are not aware of any report of a human ovarian cancer cell line for which the dose-response relationships to both radiation and chemotherapy including paclitaxel and cisplatin have been evaluated with the same methodology. The present study investigated the radiosensitivity profiles of four established human ovarian cancer cell lines in vitro using the ATP assay, which measures total cell kill. The CAOV-3 cell line showed the highest degree of radiosensitivity of the four cell lines. SKOV-3 cells were the most resistant. The BG-1 cell line, previously shown to be highly resistant to cisplatin but sensitive to paclitaxel, was distinctly sensitive to radiation. This was particularly true for the lower dosages (2-6 Gy). The four cell lines tested are a good representation of cell lines with different radiosensitivities. The different response patterns to cytotoxic agents and radiation, make the BG-1 cell line in particular an interesting candidate for future studies on mechanisms of resistance and combination effects between radiation and chemotherapy.

In vitro antigene therapy targeting HPV-16 E6 and E7 in cervical carcinoma.

Human papillomavirus (HPV) infection is believed to play a central role in cervical carcinogenesis. Specifically, two viral oncoproteins, E6 and E7, possess transforming ability and have been shown to interact with the cellular tumor suppressors p53 and p105, the retinoblastoma (Rb) gene product. To test the hypothesis that E6 and E7 play an active role in the maintenance of the malignant phenotype and may be ideal targets for antigene therapy, we tested the antiproliferative effects of phosphorothioate oligodeoxynucleotides (oligos) targeting HPV-16 E6 and E7 in cervical cancer cell lines and primary tumor explants. The ATP cell viability assay was used to measure growth effects of 27-mer antisense oligos targeting the ATG translational start region of HPV-16 E6 and E7 sequences in HPV-16-positive cell lines SiHa and CaSki and four advanced, primary cervical tumor explants. A random oligo sequence, an HPV-18-positive and HPV-negative cell line, one histologically confirmed endometrial and two ovarian tumors were used as negative controls. HPV type was confirmed by hybrid capture techniques. Cell lines and sterile (staging laparotomy) tumor cells were plated at 5000 cells/0.1 ml and 100,000 cells/0.5 ml in 96-well plates or soft agar, respectively, and incubated at 37 degrees C with a single treatment of oligos at 0-16 microM. E6/E7 combinations at a fixed ratio of 1:1 were used at 0-8 microM for each oligo. Cellular ATP was measured by luciferin/luciferase fluorescence on Day 6. HPV-16 E6 and E7 oligos showed antiproliferative effects in all HPV-16-positive cell lines and primary tumor explants (IC50s 6.9-9.5 microM for cell lines, 9.1-12.1 microM primary cervical tumors), while the HPV-negative C33-A cell line and HPV-18-positive cell line HeLa were relatively insensitive to the HPV-16 oligos (IC50s > 30 microM extrapolated). The endometrial and two ovarian primary tumors were also insensitive to the HPV E6 and E7 oligos (IC50s > 25 microM extrapolated). Random oligos had little effect on cell growth at concentrations up to 16 microM (< 25% inhibition), except in CaSki (@50% inhibition at 16 microM). Combinations of E6 and E7 demonstrated mixed synergistic and antagonistic effects as determined by combination indices (CI) derived from median effect parameters. In the HPV-16-positive primary cervical tumors and the cell line SiHa, E6/E7 combinations were synergistic at low doses (< 25% growth inhibitory dose range) and antagonistic at doses above this. For the HPV-16-positive cell line CaSki, however, E6/E7 combinations were antagonistic at all dose ranges. Phosphorothioate oligos directed against the viral oncogenes E6 and E7 were shown to have antiproliferative effects specific to HPV-containing cancer cells. These specific antiproliferative effects suggest that HPV-16 E6 and E7 sequences play an active role in the malignant growth properties of cervical cancer cells and may be ideal targets for antigene therapy.

Modulation of cisPlatin cytotoxicity by interleukin-1 alpha and resident tumor macrophages.

The modulation of cisPlatin cytotoxicity by interleukin-1 (IL-1 alpha) was studied in cultures of SCC-7 tumor cells with and without tumor macrophages to examine potential mechanisms for the synergistic antitumor activity of cisPlatin and IL-1 alpha in SCC-7 solid tumors. Neither IL-1 alpha nor tumor macrophages affected the survival of clonogenic tumor cells and IL-1 alpha had no direct effect on tumor cell growth in vitro. Macrophages had no direct effect on cisPlatin sensitivity (IC90 = 6.0 microM), but, the addition of IL-1 alpha (500-2000U/ml) to co-cultures of cisPlatin pretreated tumor cells and resident tumor macrophages increased cell killing (IC90 = 3.1 microM). Similar responses were seen in primary cultures treated with cisPlatin before IL-1 alpha. The modulation of cisPlatin cytotoxicity by IL-1 alpha exhibited a biphasic dose response that paralleled the IL-1 alpha dose dependent release of H2O2 by resident tumor macrophages. Further, IL-1 alpha modification of cisPlatin cytotoxicity was prompt and inhibited by catalase. CisPlatin and exogenous H2O2 (50 microM) produced more than additive SCC-7 clonogenic cell kill and hydroxyl radicals played an important role in the response. Interleukin-1 modulation of cisPlatin cytotoxicity was schedule dependent. IL-1 alpha treatment for 24 hrs, before cisPlatin, produced drug resistance (IC90 = 11.1 microM). Our study shows that IL-1 alpha can stimulate tumor macrophages to release pro-oxidants that modify cellular chemosensitivity in a schedule and dose dependent fashion. Our findings may also provide a mechanistic explantation for the synergistic antitumor activity of cisPlatin and IL-1 alpha in vivo.

Surgically defined prognostic parameters in patients with early cervical carcinoma. A multivariate survival tree analysis.

BACKGROUND: This study was performed to identify a statistical combination of independent pathologic and clinical features that best predict 5-year disease free survival (DFS) in patients with early stage cervical carcinoma treated by radical hysterectomy. The main goal of the study was to identify subsets of patients based on risk factors with maximal differences in DFS. METHODS: Three hundred and seventy patients were found for whom complete clinical and pathologic material, including cone and cervical biopsies, were available for analysis. Variables studied included age, weight, race, marital status, economic status, tumor size (TS), depth of invasion (DI), lymph-vascular space involvement (LVSI), cell type, tumor grade, lymph node metastasis (LNM), and number of lymph nodes removed. Patients with LNM, parametrial involvement, and positive or close surgical margins were offered postoperative radiation. After excluding patients with microinvasive and small cell carcinoma, data from the remaining 301 patients were submitted to univariate and multivariate analyses to define those variables that best predict DFS. RESULTS: Univariate analysis showed that, ranked by degree of significance, DI, TS, LVSI, LNM, tumor volume (TV) and clinical stage were significant in predicting survival. Significant (P < 0.05) single parameters and other variables considered important were chosen for multivariate analysis, including the creation of a survival tree. With this method, DI (< or = 6 mm and > 2 cm), LVSI, age (> or = 40 yrs), and LNM were found to be the best combination of risk factors to define prognosis. CONCLUSIONS: The multivariate survival tree analysis maximally separates patients with early stage invasive carcinoma of the cervix into 3 subgroups with 5-year DFS of 91%, 68%, and 43%, respectively. The authors excluded patients with microinvasive carcinoma (SGO, Society of Gynecologic Oncologists), who have an excellent DFS of 100%, and patients with small carcinoma, who have a poor DFS of 36.4% based on cell type alone, to define independent risk factors that maximally separate the remaining patients by DSF. The survival tree prognostic scoring system is easy to apply, and only requires DI (mm), LVSI (+, -), LNM, and age to assign an individual patient to one of three risk groups.

Lymph node metastases and prognosis in patients with stage IA2 cervical cancer.

Ninety-four patients with squamous cell carcinoma invading the cervical stroma to a depth of >3.0-5.0 mm with 7 mm or less in horizontal spread (FIGO Stage IA2) were evaluated. Depth and lateral extent of stromal invasion were verified using an ocular micrometer. Cell type and lymph vascular space invasion (LVSI) were recorded in each case. Patients were treated primarily by radical hysterectomy with pelvic lymphadenectomy, and those with lymph node metastases were offered postoperative radiation. Following treatment, patients were seen at 3-month intervals for 2 years, and every 6 months thereafter. The mean duration of follow-up was 6.9 years (range 0.4-23.5 years). Seven of 94 patients (7.4%) had lymph node metastases. Five patients had 1 positive node, 1 patient had 2 positive nodes, and 1 patient had 3 positive nodes. Five patients developed recurrent cancer and 4 died of disease. LVSI was present in 31 cases (33%). Tumor recurrence was significantly increased in patients with positive LVSI (9.7% vs 3.2%). The 5-year survival rate of patients with LVSI was 89% vs 98% in patients without this finding (P = 0.058). The 5-year survival rate of all Stage IA2 cervical cancer patients was 95%. Patients with Stage IA2 cervical cancer have a significant risk of lymph node metastases and should be treated by radical hysterectomy with pelvic lymphadenectomy. LVSI is an important prognostic variable in these patients and should be recorded in all cases.

Management of stage I-B, II-A, and II-B carcinoma of the cervix with high-dose-rate brachytherapy: initial results of an institutional clinical trial.

In 1989, the University of Miami began a program incorporating high-dose-rate (HDR) brachytherapy into the definitive treatment of patients with invasive carcinoma of the cervix. Patients received an average total dose to point A of 5,511 cGy (range 4,280-6,360 cGy) in an average of 57 days (range 39-84 days). An analysis of the first 24 cases found 11 FIGO Stage I-B, four Stage II-A, and nine Stage II-B tumors. At the end of all radiation therapy, 19/24 patients' tumors (79.2%) had undergone a clinical complete response (CR). With median follow-up of 26 months (range 14-63 months), three have relapsed locally, two regionally, and six in extrapelvic sites. Almost two-thirds of all failures occurred in patients with tumors >4 cm, who also took more than 8 weeks to complete their treatment. Overall 2-year actuarial survival for the entire study group is approximately 74%. A univariate analysis determined that clinical stage (P = 0.02), overall treatment time (P = 0.03), tumor size (P = 0.05), and response at the end of therapy (P = 0.005) were significant prognostic factors. Multivariate analysis showed that tumor response to therapy was the most important prognosticator of outcome (P = 0.001). Besides five cases of apical vaginal stenosis, there have been no reported chronic complications in this cohort of patients. A prospectively randomized trial is recommended to compare the efficacy of HDR vs. low-dose-rate brachytherapy in cervical carcinoma.