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Invasive cervical cancer is characterized by basement membrane-invading lesions capable of metastasizing through the lymphatic and vascular systems. Treatment methods were reviewed by panelists at the Second International Conference on Cervical Cancer (Houston, TX, April 11-14, 2002), and new opportunities for translational research were discussed. Reviews encompassed hysterectomy with or without lymph node dissection or cervical conization in cases with microinvasion and radical trachelectomy with or without lymph node dissection as fertility-sparing surgery. Chemoradiation is used to treat advanced cervical malignancies, and the risks and benefits of radiotherapy are significant. Pelvic exenteration is used to treat certain types of recurrences. Use of the Miami pouch for continent urinary diversion was highlighted. Gynecologic oncologists expect novel in vivo imaging techniques currently being developed to help guide therapy choices within the next decade. The most significant research priorities are large group-randomized trials involving fertility-sparing procedures and the management of microinvasive carcinoma (MICA); better identification of candidates for chemoradiation; and the development of innovative approaches to exenteration. Improving diagnostic technologies, refining the criteria by which therapies are chosen, and preserving fertility remain challenges in selecting the most appropriate treatment for invasive cervical cancer. Research advances in both diagnosis and treatment are expected to improve therapy and outcomes., (Copyright 2003 American Cancer Society.)

Background: Ureteral stricture is a rare late complication of curative radiotherapy for carcinoma of the cervix. A retrospective study was performed to determine the incidence and latency of radiation-induced ureteral stricture, to investigate possible contributing factors, and to compare the time course and presenting characteristics of ureteral compromise caused by late radiation injury or tumor recurrence., Methods: The records of 1784 patients with FIGO stage IB carcinoma of the cervix treated with radiotherapy at The University of Texas M. D. Anderson Cancer Center between 1960 and 1989 were reviewed. The characteristics of patients who developed ureteral stricture as a first manifestation of recurrent disease or without evidence of pelvic recurrence were compared. The risk of ureteral compromise was calculated actuarially., Results: There were 29 patients with severe radiation-induced ureteral stricture. The overall incidences of severe ureteral stenosis were 1.0, 1.2, 2.2, and 2.5% at 5, 10, 15, and 20 years, respectively, reflecting a continuous actuarial risk increase of approximately 0.15% per year. Four patients died of complications from bilateral ureteral stricture. Patients who were treated with centrally blocked external fields or who received more than two transvaginal radiation treatments were at increased risk for developing ureteral stenosis. The risk was similar for patients treated with radiation alone or followed by extrafascial hysterectomy., Conclusions: During the first 5 years after treatment, tumor recurrence is the most common cause of ureteral stricture in patients treated with radiotherapy for carcinoma of the cervix. However, radiation injury to the ureter, although rare, may not become apparent for many years, necessitating continued vigilance throughout the lives of these patients.

Background: Hyperfractionated radiation therapy (HFX), which may permit higher total doses of radiation therapy without increased toxic effects to normal tissues, has been used with pelvic tumors, but its combination with brachytherapy has not been well studied., Methods: A prospective Phase I/II trial was designed to study HFX with brachytherapy in patients with bulky Stage IB and IIA, IIB, III, and IVA carcinomas of the cervix. HFX doses of 1.2 Gy were administered to the whole pelvis twice daily at 4-6 hour intervals, 5 days per week; the total dose to the whole pelvis was 24-48 Gy. External pelvic irradiation was followed by one or two intracavitary applications to deliver the total minimum dose of 85 Gy at point A and 65 Gy to the lateral pelvic nodes., Results: Eighty-one patients were enrolled in this protocol; 14% had Stage IB, 43% stage II, 38% stage III, and 4% stage IVA carcinomas. Seventy-one patients were evaluable for HFX and brachytherapy; 38 patients received one intracavitary application, and 33 received two applications. Four patients had Grade 3 acute reactions. The cumulative rates of Grade 3-4 late toxicities were 1.9% at 1 year, and 6.3% at 2 and 3 years. Of 80 patients evaluated for response, 80% had complete disappearance of disease. Comparisons with historical rates of late toxicity with standard fractionation (STD) revealed similar results in spite of higher total doses with HFX. Comparisons between historical STD and HFX also revealed equivalent rates of pelvic tumor control, Grade 3-4 toxicity, and survival at 3 years., Conclusions: Results suggest that combined with brachytherapy, HFX at total parametrial doses 10% above those used with STD was tolerated and at least as effective as STD. Further study with higher doses and extended fields is indicated. Comparisons of long term (5-plus years) survival and late-effects rates with STD versus HFX are planned.

A retrospective chart review and questionnaire study was undertaken to look at the long-term effects of radiation therapy in ovarian dysgerminoma patients. Forty-three patients and 55 controls responded to a questionnaire that detailed bowel, bladder, thyroid, menstrual, reproductive, sexual, and growth function. Statistically significant differences in the number of bowel movements were noticed when comparing patients with controls. The authors noticed no significant differences between cases and controls in bladder function. No thyroid disorders were attributable to mediastinal radiation therapy. Most patients with intact uteri bleed monthly on hormonal replacement. Three patients with a remaining ovary and uterus resumed menstrual function after substantial doses of abdominopelvic radiation therapy. No patients have conceived. The authors noticed a slight increase in dyspareunia in the treated group, but most patients were satisfied with their sexual function. One premenarchal patient exhibited a growth disorder.

Between 1965 and 1985, 367 patients received initial treatment for adenocarcinoma of the uterine cervix at the M. D. Anderson Cancer Center (MDACC). Of the 334 patients treated with curative intent, 223 had International Federation of Gynecology and Obstetrics (FIGO) Stage I, 60 had Stage II, and 51 had Stage III/IV disease. The 5-year and 10-year relapse-free survival (RFS) rates for all patients treated for Stage I disease were 73% and 70%, respectively. RFS was strongly correlated with initial bulk of disease (P = 0.002), although locoregional control (LRC) was good in all groups: 91 patients with a normal-sized cervix (tumor less than 3 cm) had a 5-year RFS rate of 88% and an actuarial LRC rate of 94%; 102 patients with lesions 3 to 5.9 cm in diameter had an RFS rate of 64% and an LRC rate of 82%; and 22 patients with bulky lesions greater than 6 cm in diameter had a comparable LRC rate of 81%, but an RFS rate of only 45%. Decreased RFS also was strongly correlated with positive lymphangiogram (LAG) results (P = 0.02) and poorly differentiated lesions (P = 0.0014). When initial primary tumor size was taken into account, there was no significant difference in RFS or LRC between patients treated with radiation (RT) alone or RT plus extrafascial hysterectomy (R + S). The 5-year and 10-year RFS rates of 60 patients who received curative therapy for Stage II disease were 32% and 25%, respectively, with an LRC rate of 62% at 5 years. Patients with bulky Stage II disease did particularly poorly, with a 5-year RFS rate of 15%. Decreased RFS was correlated with positive LAG results and poorly differentiated tumors. Most Stage II patients whose disease relapsed died with distant metastases (73%). Forty-eight patients with Stage III/IV disease treated with curative intent had a 5-year survival rate of 31% and a 5-year pelvic disease control rate of 52%. In summary, patients with small volume Stage IB lesions have excellent LRC and survival with RT alone. RT achieves good LRC of bulkier Stage I lesions, but survival decreases with increasing primary tumor size. R + S holds no apparent advantage over RT alone. Patients with more advanced disease have a high rate of relapse with frequent distant metastasis. In particular, the survival of patients with FIGO Stage II disease is much lower than what we have observed after treatment of comparable stage squamous carcinoma.(ABSTRACT TRUNCATED AT 400 WORDS)

Between 1959 and 1975, 256 patients with pathologic Stage I uterine adenocarcinoma were treated at Stanford University Hospital, Stanford, California. One hundred ninety-three patients were initially treated with surgery, and 63 received preoperative radium, reflecting different treatment philosophies of physicians operating at Stanford. Relapse rates for the two treatment groups were 9% (17 of 193) and 14% (9 of 63), respectively (P = 0.24). In both groups of patients, relapse rates were correlated with grade, although for those treated with initial surgery myometrial invasion was a much better predictor of relapse. Only one of the 127 patients without demonstrable myometrial invasion suffered a possible relapse. Sixteen of 66 patients with myometrial invasion (24%) relapsed after treatment. A review of the histologic material revealed 26 of 256 cases with a special histologic variant termed uterine papillary serous carcinoma, which was associated with a high relapse rate (50%) and a marked tendency for upper abdominal spread. It was found that the use of preoperative intracavitary radium was not demonstrated to be of value. Histologic information obtained from the hysterectomy specimen can be used to determine patients at high risk for relapse who may benefit from adjuvant treatment based on our understanding of the natural history of endometrial carcinoma.

Twenty-nine patients had simultaneous malignant epithelial neoplasms of the uterine corpus and ovary. Three groups were defined on the basis of tumor histology: Group A: those with endometrioid carcinoma in both the uterus and ovary; Group B: those with special variants of corpus carcinoma (papillary, clear cell, mucinous) and identical neoplasms in the ovary; and Group C: those whose uterine and ovarian carcinomas were of dissimilar histologic types. Sixteen women had endometrioid carcinoma in both sites. The median age at diagnosis, 41 years, was younger than is usual for corpus or ovarian cancer. For all 16 patients, the grade of the ovarian endometrioid carcinoma was similar to that of the endometrioid carcinoma of the uterine corpus. Seven patients had bilateral ovarian neoplasms. Only one patient had myometrial invasion by the corpus carcinoma. No patient with simultaneous ovarian and uterine endometrioid carcinoma, regardless of grade, has died of cancer although one vaginal relapse was treated successfully. This excellent survival of patients with simultaneous endometrioid carcinomas is better than would be expected for either Stage III adenocarcinoma of the endometrium or Stage II ovarian carcinoma. These simultaneously occurring endometrioid neoplasms of ovary and endometrium are considered to be separate primary tumors. The morphologic reasons for this view and therapeutic implications are discussed. In contrast to the patients with endometrioid carcinoma, the eleven patients with other histologic types of carcinoma in the ovary and corpus were older (median age, 61 years) and more often postmenopausal (90%). These neoplasms were more aggressive, with frequent deep myometrial involvement (63%), tubal involvement (27%), and extension to other pelvic tissues (36%) at the time of initial diagnosis. Six of these 11 patients succumbed to their cancer despite surgical therapy and radiation. The distribution of tumor in some of these patients with nonendometrioid types of carcinoma is suggestive of a single primary with metastases. The therapeutic implications of these findings are discussed.