Small cell carcinoma of the ovary-hypercalcemic type (SCCOHT): A review of 47 cases.

OBJECTIVE: Small cell carcinoma of the ovary-hypercalcemic type (SCCOHT) is a rare disease with a poor prognosis. SCCOHT has recently been shown to be associated with SMARCA4 gene mutations as well as molecular and genetic similarities to malignant rhabdoid tumors (MRT). The objective of our study is to describe the clinical characteristics, treatment modalities and outcomes of 47 patients with SCCOHT. METHODS: We performed a retrospective analysis of 47 patients with SCCOHT evaluated at MD Anderson Cancer Center between 1990 and 2014. Medical records were reviewed for demographic information, pathologic findings, treatment regimens and outcomes. RESULTS: Median age at diagnosis was 30 years (range 5-46). All patients underwent surgery with unilateral salpingo-oophorectomy (USO) performed in 26 patients (55%), and hysterectomy with bilateral salpingooophorectomy (BSO) in 21 patients (45%). Sixteen patients (34.0%) had stage I disease, six (12.8%) stage II, 23 (48.9%) stage III, and two patients (4.3%) had stage IV disease. Information on adjuvant treatment was available for 43 patients: 83.3% received chemotherapy alone, 9.5% chemotherapy followed by radiotherapy, 2.4% chemoradiation, and 4.8% did not receive any adjuvant therapy. Median follow-up was 13.2 months (range, 0.1 to 210.7) with a median overall survival of 14.9 months. Multi-agent chemotherapy and radiotherapy were associated with a better prognosis. CONCLUSION: Our findings suggest that aggressive therapy including multi-agent chemotherapy and possibly radiotherapy may extend survival. Further study is needed to improve outcomes in these patients including the adoption of systemic therapies used in MRT as well as the development of novel agents targeting specific mutations.

Time course and outcome of central recurrence after radiation therapy for carcinoma of the cervix.

We investigated the time course of central disease recurrence (CDR) in 2997 patients treated with radiation for stage I-II squamous cell carcinoma of the cervix. CDR rates were 6.8%, 7.8%, and 9.6%, at 5, 10, and 20 years, respectively. The risk of CDR was independently correlated with tumor size (P < 0.0001) but not with FIGO stage. The hazard rate peaked in the first year of follow-up and then fell steeply; after 3 years, the hazard rate was approximately constant at 0.2-0.4% per year. Although after 3 years the risk of CDR was low, it continued to be slightly greater for patients with tumors > or =5 cm than for those with smaller tumors (P= 0.001). Patients who had CDR < 36 months after treatment were less likely to be candidates for salvage therapy and had a poorer post-recurrence survival rate than those with recurrence > or =36 months after treatment (4.5% versus 42.1%, P < 0.0001). The higher rate of CDR in the first 3 years and the poor survival after early recurrence suggest that most early CDRs are true relapses. The relatively stable annual actuarial risk between 3 and 25 years and the better survival rate after late CDR suggest that most "recurrences" after 3 years are actually new neoplasms.

Heterogeneity of stage IIIA endometrial carcinomas: implications for adjuvant therapy.

The purpose of this study was to evaluate overall survival (OS) and determine prognostic subclassifications for stage IIIA endometrial cancer. Stage IIIA endometrial cancer patients treated at M.D. Anderson Cancer Center from 1989 to 2002 were reviewed. Clinical information was obtained from the medical record. Cox regression analyses were performed to evaluate the association of pathologic criteria and OS. Patients were divided into four groups based on this analysis: E1, endometrioid/pelvic cytology only; E2, endometrioid/adnexa +/- serosal spread; NE1, nonendometrioid/pelvic cytology only; and NE2, nonendometrioid/adenexa +/- serosal spread. Forty-nine patients were identified. By multivariate analysis, histology and extent of disease were the only factors associated with OS. Five-year OS in the four subgroups based on histology and extent of disease were: E1, 79%, E2, 65%, NE1, 64%, and NE2, 13%. Histologic subtype and extent of pelvic disease are the only prognostic factors associated with OS. Patients with endometrioid tumors and extent of pelvic disease limited to positive cytology had a favorable outcome, with or without adjuvant therapy. Future prospective clinical trials should consider subclassifying patients with stage IIIA disease to better evaluate the role of adjuvant therapy.

Utility of lymphangiography in the prediction of lymph node metastases in patients with cervical cancer.

Our objective was to assess the value of lymphangiography in selecting patients for surgical staging of locally advanced cervical cancer. We reviewed our computerized database to identify patients with cervical cancer who had abnormal findings on lymphangiography and underwent retroperitoneal lymph node dissection between September 1991 and January 1996. The records of these patients were retrospectively reviewed, and the following data were retrieved: clinical tumor stage and findings on lymphangiography at surgery, and on pathologic examination of resected lymph nodes. The lymphangiograms were reviewed and reinterpreted in blinded fashion by two of the authors. The positive and negative predictive values of lymphangiography for the presence of lymph node metastases were calculated, with findings on pathologic examination of lymph nodes used as the gold standard. The positive and negative predictive values of surgeons' clinical assessments at surgery were also calculated. Fifty patients met the selection criteria and constituted the study population. Fourteen patients (28%) had histologically negative nodes, and 36 patients (72%) had lymph node metastases. Thirty-three patients had metastases to pelvic nodes, 1515 patients had metastases to common iliac nodes, and 1616 patients had metastases to para-aortic nodes. The positive predictive value of lymphangiography for lymph node metastases was 74% for pelvic nodes, 73% for common iliac nodes, and 88% for para-aortic nodes. The negative predictive value of lymphangiography for lymph node metastasis was 76% for common iliac nodes and 77% for para-aortic nodes. Overall, 46% of the patients selected for surgical exploration had histologic findings of either common iliac or para-aortic lymph node metastases; these findings led clinicians to extend radiation fields to cover the para-aortic lymph nodes. Lymphangiography is helpful in selecting patients with cervical cancer who have a high risk of common iliac or para-aortic lymph node metastasis. However, more accurate and more readily available noninvasive methods of evaluating cervical patients for the presence of regional disease continue to be needed.

Long-term follow-up of RTOG 92-10: cervical cancer with positive para-aortic lymph nodes.

PURPOSE: The purpose of this study was to evaluate the late toxicity and efficacy of twice-daily external irradiation to the pelvis and lumbar para-aortic region with brachytherapy and concurrent chemotherapy for carcinoma of the cervix with positive para-aortic lymph nodes. PATIENTS AND METHODS: This study was designed to administer twice-daily radiation doses of 1.2 Gy to the pelvis and lumbar para-aortic lymph nodes (simultaneously) at 4-6-h intervals, 5 days per week. The total external radiation doses were 24-48 Gy to the whole pelvis, 12-36 Gy parametrial boost, and 48 Gy to the lumbar para-aortic region with an additional boost to a total dose 54-58 Gy to the positive para-aortic lymph node(s). One or two intracavitary implants were performed to deliver a minimum total dose of 85 Gy to point A. Cisplatin (75 mg/m(2); Days 1, 22, and 43) and 5-fluorouracil (1,000 mg/m(2)/24 h x 4 consecutive days, beginning on Days 1, 22, and 43) were given for two or three cycles. RESULTS: Thirty patients with clinical Stages I-IV carcinoma of the cervix with biopsy-proven para-aortic lymph node metastases were enrolled in this study. Hyperfractionated external irradiation was completed in 87% (26 of 30). Brachytherapy was given in two implants to 47% (14 of 30) and in one implant to 33% (10 of 30); 13% (4 of 30) did not receive brachytherapy, 1 patient had three implants, and 1 had five high-dose-rate implants. Radiotherapy was completed per protocol in 70%. Three cycles of chemotherapy were given to 23% (7 of 30); 73% (22 of 30) received two cycles, and 1 patient did not receive chemotherapy. The acute toxicity from chemotherapy was Grade 1 in 3%, Grade 2 in 17%, Grade 3 in 48%, and Grade 4 in 28%. Acute toxicity from radiotherapy was Grade 1 in 7%, Grade 2 in 34%, Grade 3 in 21%, and Grade 4 in 28%. Late toxicity was Grade 1 in 10%, Grade 2 in 17%, Grade 3 in 7%, and Grade 4 in 17%. Grade 5 toxicity occurred in 1 patient during the course of therapy, but none had a late Grade 5 toxicity. The median follow-up time for the 7 patients alive at the time of last follow-up was 57 months. The overall survival estimates were 46% at 2 years and 29% at 4 years. The probability of local-regional failure was 40% at 1 year and 50% at 2 and 3 years. The probability of disease failure at any site was 46% at 1 year, 60% at 2 years, and 63% at 3 years. CONCLUSION: The results suggest that twice-daily external irradiation to the pelvis and lumbar para-aortic region with brachytherapy and concurrent chemotherapy resulted in an unacceptably high rate (17%, 5 of 29) of Grade 4 late toxicity. One patient died of acute complications of therapy. The survival estimates seem no better than standard fractionation irradiation without chemotherapy.

National Institutes of Health Consensus Development Conference Statement: adjuvant therapy for breast cancer, November 1-3, 2000.

OBJECTIVE: Our goal was to provide health-care providers, patients, and the general public with an assessment of currently available data regarding the use of adjuvant therapy for breast cancer. PARTICIPANTS: The participants included a non-Federal, non-advocate, 14-member panel representing the fields of oncology, radiology, surgery, pathology, statistics, public health, and health policy as well as patient representatives. In addition, 30 experts in medical oncology, radiation oncology, biostatistics, epidemiology, surgical oncology, and clinical trials presented data to the panel and to a conference audience of 1000. EVIDENCE: The literature was searched with the use of MEDLINE(TM) for January 1995 through July 2000, and an extensive bibliography of 2230 references was provided to the panel. Experts prepared abstracts for their conference presentations with relevant citations from the literature. Evidence from randomized clinical trials and evidence from prospective studies were given precedence over clinical anecdotal experience. CONSENSUS PROCESS: The panel, answering predefined questions, developed its conclusions based on the evidence presented in open forum and the scientific literature. The panel composed a draft statement, which was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. The draft statement was made available on the World Wide Web immediately after its release at the conference and was updated with the panel's final revisions. The statement is available at http://consensus.nih.gov. CONCLUSIONS: The panel concludes that decisions regarding adjuvant hormonal therapy should be based on the presence of hormone receptor protein in tumor tissues. Adjuvant hormonal therapy should be offered only to women whose tumors express hormone receptor protein. Because adjuvant polychemotherapy improves survival, it should be recommended to the majority of women with localized breast cancer regardless of lymph node, menopausal, or hormone receptor status. The inclusion of anthracyclines in adjuvant chemotherapy regimens produces a small but statistically significant improvement in survival over non-anthracycline-containing regimens. Available data are currently inconclusive regarding the use of taxanes in adjuvant treatment of lymph node-positive breast cancer. The use of adjuvant dose-intensive chemotherapy regimens in high-risk breast cancer and of taxanes in lymph node-negative breast cancer should be restricted to randomized trials. Ongoing studies evaluating these treatment strategies should be supported to determine if such strategies have a role in adjuvant treatment. Studies to date have included few patients older than 70 years. There is a critical need for trials to evaluate the role of adjuvant chemotherapy in these women. There is evidence that women with a high risk of locoregional tumor recurrence after mastectomy benefit from postoperative radiotherapy. This high-risk group includes women with four or more positive lymph nodes or an advanced primary cancer. Currently, the role of postmastectomy radiotherapy for patients with one to three positive lymph nodes remains uncertain and should be tested in a randomized controlled trial. Individual patients differ in the importance they place on the risks and benefits of adjuvant treatments. Quality of life needs to be evaluated in selected randomized clinical trials to examine the impact of the major acute and long-term side effects of adjuvant treatments, particularly premature menopause, weight gain, mild memory loss, and fatigue. Methods to support shared decision-making between patients and their physicians have been successful in trials; they need to be tailored for diverse populations and should be tested for broader dissemination.

Sigmoid perforation following radiation therapy in patients with cervical cancer.

OBJECTIVE: We describe the clinical presentation, evaluation, management, and outcome of patients experiencing sigmoid perforation following radiation therapy for cervical cancer. METHODS: A database consisting of over 5000 patients with stage IB-IIIB cervix cancer treated between 1963 and 1992 revealed 35 patients with sigmoid perforation. Twenty-seven were diagnosed and managed at one institution, and they form the study group. RESULTS: The median age at the time of perforation was 50 years, and the median follow-up care was 78 months (range 6-396). The median time from completion of radiotherapy to perforation was 13 months (range 3-98). The mean interval from the first documented complaint to the index admission was 90 days. Nine (33%) of 27 patients were treated with high-dose radiation therapy. The most common complaint was abdominal pain in 25 (93%) patients, nausea occurred in 12 (44%) patients, weight loss in 12 (44%) patients, and vomiting in 10 (37%) patients. The pain was described as mild in 16 (73%) of 22 patients. Only 5 (18.5%) of 27 patients had physical signs of acute peritonitis, 8 (30%) of 27 patients had some form of tenderness, and 11 (41%) of 27 had a benign exam. A total of 20 (74%) patients had an abdominal radiograph, and 12 (44%) patients had a contrast enema for evaluation. Evidence of perforation was present in 5 (25%) of 20 plain abdominal radiographs and 1 (8%) of 12 contrast enemas. Following admission, 17 (63%) patients were observed initially with subsequent surgery after symptoms either failed to resolve or worsened. The median duration under observation was 4 days (range 1-23). Surgery was performed immediately in 8 patients (30%), and 2 (7%) were observed without operation. In these 2 patients, perforation was diagnosed postmortem. Seventeen (68%) of 25 patients had a localized abscess. Three of the patients who underwent immediate exploration and 7 who had surgery after a period of observation died postoperatively (10/25, 40%). Five (55%) of 9 patients in the group who received high-dose radiation therapy died because of sigmoid perforation. When the time frame of presentation was evaluated, we noted that 10 (50%) of 20 patients died between 1960 and 1979 and 1 (14%) of 7 died between 1980 and 1992. CONCLUSIONS: Sigmoid perforation following pelvic radiation for cervical cancer does not usually present with the typical signs of a ruptured viscus. A high degree of suspicion remains a priority in the care of radiated patients who present with abdominal pain given the atypical presentation of perforation in this group.

Combined radiation therapy and chemotherapy for carcinoma of the cervix.

Cervical cancer is the third most common cancer affecting women worldwide. Surgery, radiation therapy, and chemotherapy have been used in various settings in an effort to improve survival rates of patients with cervical cancer. Recent cooperative clinical trials have demonstrated a benefit from the concurrent use of chemotherapy and radiation therapy to treat cervical cancer. These studies have provided the most significant improvement in the treatment of locally advanced disease in more than 30 years. This review summarizes studies of sequential and concurrent combinations of chemotherapy and radiation therapy for the treatment of cervical cancer, as well as the recent controversies related to this treatment.

Quantification of intracavitary brachytherapy parameters and correlation with outcome in patients with carcinoma of the cervix.

PURPOSE: To quantify the M. D. Anderson criteria for acceptable implant geometry; to relate our system of intracavitary radiotherapy (ICRT) prescription to Manchester and ICRU reference doses; and to correlate these parameters with outcome measures. METHODS AND MATERIALS: The relationships between intracavitary applicators and normal structures were measured directly from localization films of 808 applications performed in 396 patients who completed definitive treatment for cervical cancer between 1990 and 1994. The distances between applicators and tissue landmarks and the doses to Manchester and normal tissue reference points were correlated with outcome. RESULTS: The median distance from the tandem to the sacrum was 4.0 cm, or one-third the distance from the pubis to the sacrum. The mean distance between the vaginal ovoids and cervical marker seeds was 7 mm, and the median distance between the tandem and the posterior edge of the ovoids was 50% of the ovoid length. In 92% of insertions, vaginal packing was posterior to or within 5 mm of a line that passed through the posterior edge of the ovoids, parallel to the tandem. The median doses to Point A and rectal, bladder, and vaginal surface reference points were 87 Gy, 68 Gy, 70 Gy, and 125 Gy, respectively. Although these reference doses were not routinely used to prescribe treatment, consistent applicator geometry and source selection resulted in a relatively narrow range of delivered doses. The average ratios between the doses at bladder or rectal reference points and Point A were somewhat greater when smaller vaginal applicators were used. Patients received a median of 5600 mgRaEq-h from ICRT. The total mgRaEq-h were correlated with but were not proportional to the dose at Point A. There were no significant correlations between the doses to standard reference points and the rates of central recurrence or major complications. CONCLUSION: When ICRT implants are carefully placed, relatively high paracentral doses can be delivered that yield a high rate of central disease control with an acceptable rate of complications. The narrow range of doses delivered to standard reference points and their inconsistent correlation with the maximum doses delivered to normal tissues probably contributed to a lack of correlation between reference doses and outcome.

Chemoradiation for carcinoma of the cervix: advances and opportunities.

Although it is possible to cure many patients with locally advanced cervical cancer using radiation therapy alone, loco-regional relapse continues to be a component of most recurrences. To improve control rates, clinicians have investigated ways of combining chemotherapy and radiation for more than 30 years. Despite encouraging results from phase II trials of neoadjuvant chemotherapy, randomized trials failed to improve on the results with radiation therapy alone. For a number of reasons, early trials of concurrent chemoradiation were inconclusive. However, recent reports of five large prospective randomized trials demonstrated dramatic improvements in survival and local control rates when cisplatin-containing chemotherapy was given during radiation therapy. These results also suggest a number of avenues for future research.

Posttherapy surveillance of women with cervical cancer: an outcomes analysis.

OBJECTIVE: The aim of this study was to develop a surveillance program that optimizes clinical outcome following primary treatment of women with cervical cancer. METHODS: The records of 1096 patients with FIGO stage IB cervical cancer treated from 1983 to 1993 were retrospectively reviewed. Recurrence was analyzed by site, presence or absence of symptoms, method of detection, and survival. Univariate and multivariate analyses using a Cox proportional hazards model were performed. RESULTS: One hundred thirty-three patients (13%) developed recurrent disease. Of these, 114 were symptomatic and 19 were asymptomatic at the time of recurrence. Thirty-seven patients recurred in the central pelvis, 21 each in the lung or pelvic wall, 22 in nodes, and 35 in other sites. The median disease-free interval was 17 months for symptomatic patients and 16 months for asymptomatic patients. The median survival from initial diagnosis was 31 months for symptomatic and 83 months for asymptomatic patients (P = 0.001). The median survival from recurrence was 11 months for symptomatic and 42 months for asymptomatic patients (P < 0.001). Multivariate analysis revealed that symptom status at time of recurrence was a significant predictor of survival, even when known prognostic factors were considered (P < 0.001). All asymptomatic pelvic recurrences were diagnosed by pelvic exam; all asymptomatic pulmonary recurrences were detected by chest radiographs. Pap smears did not detect a single asymptomatic recurrence. CONCLUSIONS: Posttherapy surveillance programs are directed toward asymptomatic patients in whom early detection of recurrence may impact survival. These data indicate that a subset of women may benefit from surveillance. A model for surveillance is proposed.

Socioeconomic characteristics of patients with squamous cell carcinoma of the uterine cervix treated with radiotherapy in the 1992 to 1994 patterns of care study.

PURPOSE: To describe the relationship between socioeconomic variables and the treatment of patients with radiotherapy for cervix cancer.40% minority patients. METHODS AND MATERIALS: Sixty-two institutions werw r andomly selected from a list of all radiotherapy facilities in the Unite d States. From these we randomly selected and reviewed 471 cases of squ amous cell carcinoma treated during 1992 to 1994. To create an addition al minority-rich sample, we randomly selected 215 additional cases from 17 randomly selected institutions that admitted >40% minority patients. The median household income of each patient's neighborhood was determined by matching her zip code to data from the 1990 United States Census. RESULTS: Pati ents who lived in low-income neighborhoods, who had only Medicaid covera ge, or who were treated at large academic or minority-rich institutions tended to have a poorer initial performance status, higher-stage or bulk y central disease, and a lower pretreatment hemoglobin level. Ability t o complete treatment did not correlate with ethnicity or income. Howeve r, noncompliant patients tended to be treated at minority-rich instituti ons and were more often < 40 or > 60 years old. Patients who completed definitive treatment were more likely to have had

Perioperative and postoperative complications of intracavitary radiation for FIGO stage I-III carcinoma of the cervix.

PURPOSE: To evaluate perioperative and postoperative complications of low-dose-rate (LDR) intracavitary radiation therapy in patients with FIGO Stage I-III carcinoma of the uterine cervix. METHODS AND MATERIALS: We retrospectively reviewed the medical and radiotherapy records of all patients treated with radiation between 1960 and 1992 at The University of Texas M. D. Anderson Cancer Center for FIGO I-III carcinomas of the cervix. Patients who had had initial hysterectomy or whose treatment did not include intracavitary irradiation were excluded. The final study included 4043 patients who had undergone 7662 intracavitary procedures. RESULTS: Eleven (0. 3%) patients had documented or suspected cases of thromboembolism resulting in 4 deaths. Of these 11 patients, 8 had clinical or radiographic evidence of tumor involving pelvic nodes or fixed pelvic wall. The risk of postoperative thromboembolism did not decrease significantly with the routine use of mini-dose heparin prophylaxis (p = 0.3). Other life-threatening perioperative complications included myocardial infarction (1 death in 5 patients), cerebrovascular accident (2 patients), congestive heart failure or atrial fibrillation (3 patients), and halothane liver toxicity (2 deaths in 2 patients). Intraoperative complications included uterine perforation (2.8%) and vaginal laceration (0.3%), which occurred more frequently in patients >/= 60 years old (p < 0.01). Fourteen percent of patients had a temperature >/= 101 degrees F during at least one hospital stay. The only correlation between minor intraoperative complications and disease-specific survival was found in patients who had Stage III disease and uterine perforation; survival was significantly (p = 0.01) decreased in these patients. CONCLUSIONS: Fatal or life-threatening complications of intracavitary treatment were very rare. Deep venous thrombosis (DVT) and pulmonary embolism (PE) did not occur in otherwise healthy patients with early disease and were rare even when disease was more advanced. Minor perioperative complications were not correlated with serious late complications or with death from disease.

Mature results of a pilot study of pelvic radiotherapy with concurrent continuous infusion intra-arterial 5-FU for stage IIIB-IVA squamous cell carcinoma of the cervix.

PURPOSE: To evaluate the long-term results of continuous infusion intra-arterial 5-fluorouracil (CI IA 5-FU) given with concurrent pelvic radiotherapy (RT) for FIGO stage IIIB-IVA carcinoma of the cervix. METHODS AND MATERIALS: Between 1965 and 1974, 27 patients with extensive FIGO Stage IIIB (22 patients) or Stage IVA (5 patients) squamous cell carcinoma of the cervix were treated with CI IA 5-FU and RT. Twenty-one patients (78%) had bilateral pelvic wall involvement, 25 (93%) had massive tumors (> or =8 cm in diameter), 7 (27%) had involvement of the lower one-third of the vagina, and 15 (56%) presented with hydronephrosis. All patients underwent routine clinical staging, transperitoneal para-aortic lymph node dissection, and bilateral hypogastric artery catheter placement. 5-FU was continuously infused at a dose rate of 10 mg/kg/day on Days 1-15 of RT. The median dose of 5-FU was 376 mg/m2/day (range 270-692). All patients received concurrent pelvic RT to a median dose of 50 Gy at 2.0 Gy per fraction. Only 4 patients received intracavitary RT. The median follow-up of surviving patients was 190 months. RESULTS: The overall 5-year survival rate was 37%. For the 22 patients with FIGO Stage IIIB disease, the 5-year survival rate was 41%. The survival rate for 18 patients treated with only external beam radiation and chemotherapy for Stage IIIB disease was 33%. Four of 10 patients treated with only 50 Gy of external beam radiation and CI IA 5-FU were long-term survivors. Acute complications, including hematologic toxicity and skin reactions, were severe, with 1 death from neutropenic sepsis. Severe late complications were only observed in patients treated with > or =60 Gy of external beam radiation. CONCLUSIONS: While this series is small, the fact that 4 patients with massive Stage IIIB tumors survived after a total radiation dose of only 50 Gy suggests that RT with CI IA 5-FU deserves further study. Modifications in dose, technique, and route of administration should reduce toxicity, and the addition of intracavitary RT should improve the local effectiveness of combined treatment.

Low dose rate brachytherapy in the treatment of cervical carcinoma.

The use of ICRT is a critical component in the successful treatment of cervical carcinoma with radiation therapy. Low dose rate ICRT allows optimization of the therapeutic ratio by utilizing physical and radiobiological principles. An optimal geometric relationship among the intracavitary applicators, the tumor, and other pelvic tissues is critically important in maximizing tumor control rates while simultaneously minimizing normal tissue complication rates. Treatment policies that have judiciously combined EBRT and LDR ICRT have achieved very high tumor control rates while maintaining acceptable complication rates. The use of HDR ICRT forfeits some of the radiobiological advantage of LDR ICRT. It remains to be determined whether this difference will have significant clinical consequences.

Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer.

BACKGROUND AND METHODS: We compared the effect of radiotherapy to a pelvic and para-aortic field with that of pelvic radiation and concurrent chemotherapy with fluorouracil and cisplatin in women with advanced cervical cancer. Between 1990 and 1997, 403 women with advanced cervical cancer confined to the pelvis (stages IIB through IVA or stage IB or IIa with a tumor diameter of at least 5 cm or involvement of pelvic lymph nodes) were randomly assigned to receive either 45 Gy of radiation to the pelvis and para-aortic lymph nodes or 45 Gy of radiation to the pelvis alone plus two cycles of fluorouracil and cisplatin (days 1 through 5 and days 22 through 26 of radiation). Patients were then to receive one or two applications of low-dose-rate intracavitary radiation, with a third cycle of chemotherapy planned for the second intracavitary procedure in the combined-therapy group. RESULTS: Of the 403 eligible patients, 193 in each group could be evaluated. The median duration of follow-up was 43 months. Estimated cumulative rates of survival at five years were 73 percent among patients treated with radiotherapy and chemotherapy and 58 percent among patients treated with radiotherapy alone (P=0.004). Cumulative rates of disease-free survival at five years were 67 percent among patients in the combined-therapy group and 40 percent among patients in the radiotherapy group (P<0.001). The rates of both distant metastases (P<0.001) and locoregional recurrences (P<0.001) were significantly higher among patients treated with radiotherapy alone. The seriousness of side effects was similar in the two groups, with a higher rate of reversible hematologic effects in the combined-therapy group. CONCLUSIONS: The addition of chemotherapy with fluorouracil and cisplatin to treatment with external-beam and intracavitary radiation significantly improved survival among women with locally advanced cervical cancer.

Radiation treatment of advanced or recurrent granulosa cell tumor of the ovary.

BACKGROUND: Because granulosa cell tumors of the ovary are rare, the optimal treatment for women with gross residual disease after primary surgery or recurrence is not known. Our objective was to review the results of radiotherapy for advanced or recurrent granulosa cell tumor of the ovary. METHODS: This retrospective review identified 34 patients with ovarian granulosa cell tumors treated with radiation at the University of Texas M. D. Anderson Cancer Center between 1949 and 1988. Fourteen received treatment for clinically measurable disease; 20 received adjuvant radiotherapy after surgery for minimal residual (<1 cm) or microscopic residual disease. The 14 patients with measurable disease formed the basis for this review. RESULTS: Ten of 14 patients were treated with moving-strip whole-abdomen radiation (27-28 Gy), 9 with 60Co, and 1 with 6-MeV photons and a pelvic boost of 28 Gy with 22-25 MeV photons. The other 4 patients were treated with pelvic radiotherapy (45-61 Gy) with 22-25 MeV photons. Six of 14 patients (43%) had a clinical complete response to radiotherapy, with a median follow-up of 13 years (range, 5-21 years). Three of 6 who responded to radiation had relapse 4-5 years later; 2 of these 3 died of disease and 1 was alive with disease at last follow-up. Three responders remain alive without evidence of disease 10-21 years after treatment. The 8 nonresponders had a median survival of 12.3 months (range, 1-60 months). CONCLUSIONS: Radiotherapy can induce a clinical response with occasional long-term remission in patients with persistent or recurrent granulosa cell tumor of the ovary.