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.

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.

Figo IIIB squamous cell carcinoma of the cervix: an analysis of prognostic factors emphasizing the balance between external beam and intracavitary radiation therapy.

PURPOSE: To define patient, tumor, and treatment factors that influence the outcome of patients with FIGO Stage IIIB squamous cell carcinoma of the intact uterine cervix. METHODS AND MATERIALS: The records of 1,096 patients treated with radiation therapy between 1960 and 1993 for FIGO Stage IIIB squamous cell carcinoma of the intact uterine cervix were reviewed retrospectively. Of these, 983 (90%) were treated with curative intent and 113 were treated only to achieve palliation of symptoms. Of 907 patients who completed the intended curative treatment, 641 (71%) were treated with a combination of external beam irradiation (EBRT) and intracavitary irradiation (ICRT) and 266 (29%) were treated with EBRT only. The median duration of treatment for these 907 patients was 51 days. Between 1966 and 1980, only 52% of patients who completed treatment with curative intent received ICRT, compared with 92% of patients treated during 1981-1993, an increase that reflects an evolution in the philosophy of treatment for advanced tumors. In general, the intensity of ICRT correlated inversely with the dose of EBRT to the,central pelvis. Median follow-up of surviving patients was 134 months. RESULTS: For 983 patients treated with initial curative intent, disease-specific survival (DSS) was significantly worse for those who were < 40 years old, had experienced more than a 10% weight loss, or had a hemoglobin level < 10 g/dl before or during radiation therapy. Tumor factors that correlated with a relatively poor DSS were bilateral pelvic wall involvement, clinical tumor diameter > or = 8 cm, hydronephrosis, lower vaginal involvement, and evidence of lymph node metastases on lymphangiogram (p < 0.01 in all cases). For the 907 patients who completed treatment with curative intent, 641 who had ICRT had a DSS of 45% at 5 years, compared with 24% for those treated with EBRT alone (p < 0.0001). Those who received > 52 Gy of EBRT to the central pelvis had DSS rates of 27-34%, compared with 53% for patients treated with lower doses of EBRT to the central pelvis and more intensive ICRT (p < 0.0001). At 5 years, the actuarial risk of major complications was also greater for patients treated with > 52 Gy of EBRT to the central pelvis (57-68%), compared with those who had 48-52 Gy (28%) and those who had < or = 47 Gy of EBRT to the central pelvis (15%) (p < 0.0001). Outcome was also compared for four time periods during which different treatment policies were in place for patients with Stage IIIB disease. The highest DSS (51%) and lowest actuarial complication rate (17%) were achieved during the most recent period (1981-1993) when modest doses of EBRT were combined with relatively intensive ICRT (p < 0.01 for both comparisons). CONCLUSION: Aggressive use of ICRT, carefully balanced with pelvic EBRT, is necessary to achieve the best ratio between tumor control and complications for patients with FIGO Stage IIIB carcinoma of the cervix. In our experience, the highest DSS rates and the lowest complication rates were achieved with a combination of 40-45 Gy of EBRT combined with ICRT.

Patterns of radiotherapy practice for patients with squamous carcinoma of the uterine cervix: patterns of care study.

PURPOSE: To determine the impact of research findings and evolving technology on the patterns of radiotherapy practice for patients with carcinoma of the uterine cervix. METHODS AND MATERIALS: Sixty-two radiation therapy facilities participated in the study after having been selected from a random sample, proportionally stratified according to practice type, of all United States facilities. Each facility submitted a list of patients treated during 1992-1994 with radiation for squamous carcinoma of the cervix. Cases for review were randomly selected from each institution after excluding those of patients who had distant metastases or initial hysterectomy. A total of 471 patients' records were reviewed in the treating institutions to obtain information about patients' characteristics, diagnostic evaluation, tumor extent, treatment approach, and radiotherapy techniques. RESULTS: Of the 61 facilities that treated eligible cases of intact cervical cancer during the 3-year survey period, 35 (57%) treated fewer than three eligible patients per year. Thirty-four (83%) of 41 non-academic facilities vs. 1 (5%) of 20 academic facilities treated fewer than three patients per year. FIGO stages were I, II, III, and IV in 32%, 40%, 24%, and 3% of patients, respectively. Computed tomography (CT) was the most common method of lymph node evaluation, but surgical evaluation, which was performed in 76 (16%) patients, had increased from previous surveys. Fields were designed using a dedicated simulator in 95% of patients; a dedicated CT unit was used for treatment planning in 119 (30%) cases. External beam irradiation was most often given using a four-field technique at 180 cGy per day on a 10-20 MV linear accelerator. The average daily fraction size had decreased from previous surveys, and 13% of patients were treated with daily doses of 170 cGy or less. Most patients were treated with a combination of external beam and low dose-rate (LDR) intracavitary irradiation. Of 425 patients who had treatment with curative intent that included brachytherapy, 362 (85%) had LDR brachytherapy, 45 (11%) had high dose-rate (HDR) brachytherapy, 3 had a combination of HDR and LDR, and 15 had incomplete information about the brachytherapy dose-rate. Forty-six (23%) of 197 patients with Stages I-IIA disease were treated with radiation followed by extrafascial hysterectomy. Of 111 patients treated with curative intent for Stage III-IV disease, 72 (65%) had a combination of external beam and intracavitary radiation therapy, 22 (20%) had external beam plus interstitial brachytherapy, and 17 (15%) were treated with external beam irradiation only. For patients who completed treatment with curative intent and did not have adjuvant hysterectomy or HDR brachytherapy, the median total dose at point A was 82.5 Gy. For all patients who completed treatment with radiation alone, the median total duration of treatment was 63 days; more than 70 days were taken to complete treatment in 33% of cases. Twenty-nine percent of patients received chemotherapy, usually concurrent with their radiation therapy. Only 27% of these patients were on investigational protocols. CONCLUSIONS: Greater participation in well-designed prospective trials might help clinicians address important clinical questions and reduce current inconsistencies in the use of adjuvant treatments. Radiation oncologists should take steps to avoid unnecessary treatment protraction and to improve patient compliance. Future studies will be needed to determine whether the small number of cases being treated in most nonacademic facilities will influence the outcome for patients with invasive cervical carcinoma.

Radiation therapy of pelvic recurrence after radical hysterectomy for cervical carcinoma.

OBJECTIVES: To evaluate the efficacy of radiation therapy and potential prognostic factors in patients treated for pelvic recurrence of cervical carcinoma after radical hysterectomy. MATERIALS: The records of 50 patients treated between 1964 and 1994 for an isolated pelvic recurrence of cervical carcinoma a median of 10.5 months after initial radical hysterectomy were retrospectively reviewed. Patients were categorized according to the extent of disease on clinical examination as group 1, mucosal involvement only (5); group 2, paravaginal extension (11); group 3, central recurrence with pelvic wall extension (13); and group 4, recurrences limited to the pelvic sidewall (21). Seven patients with group 3 or 4 disease who had a poor performance status were treated with palliative intent using hypofractionated radiotherapy. The remaining 43 patients were treated with curative intent, 33 with radiotherapy only and 10 with a combination of cisplatin-based chemotherapy and radiotherapy. Survival rates were calculated from the date of initial recurrence. Median follow-up of surviving patients was 109 months. RESULTS: The overall 5-year survival rate was 33% for all 50 patients (median survival, 18 months), 39% for the 43 patients treated with curative intent, and 25% for patients with isolated sidewall recurrences treated with curative intent. The survival rate was 69% for patients with group 1 and 2 disease and 18% for those treated with curative intent for group 3 disease (P = 0.07). The survival rate was better for patients with recurrent squamous carcinomas (51%) than for those with adenocarcinomas (14%) (P = 0. 05). Three group 4 patients who survived more than 5 years were treated with external-beam radiation alone. Eight-one percent of patients who had a second recurrence had evidence of disease progression. Three patients experienced late treatment complications. CONCLUSIONS: Patients who experience an isolated recurrence of cervical cancer after initial radical hysterectomy have an excellent prognosis if disease does not involve the pelvic wall. Occasional long-term survivors of recurrent disease involving the pelvic wall justify an aggressive treatment approach.

Twice-daily fractionation of external irradiation with brachytherapy and chemotherapy in carcinoma of the cervix with positive para-aortic lymph nodes: Phase II study of the Radiation Therapy Oncology Group 92-10.

PURPOSE: The purpose of this study was to evaluate the toxicity and efficacy of twice-daily external irradiation to the pelvis and para-aortics with brachytherapy and concurrent chemotherapy for carcinoma of the cervix with positive para-aortic lymph nodes. METHODS AND MATERIALS: This study was designed to administer twice-daily radiation doses of 1.2 Gy to the pelvis and para-aortics at 4- to 6-h intervals, 5 days per week. The total external radiation doses were 24 to 48 Gy to the whole pelvis, 12 to 36 Gy parametrial boost, and 48 Gy to the para-aortics with an additional boost to a total dose of 54 to 58 Gy to the known metastatic para-aortic site. One or two intracavitary applications were performed to deliver a total minimum dose of 85 Gy to point A. Cisplatin (75 mg/m2, days 1 and 22) and 5-FU (1000 mg/m2/24 h x 4 days; days 1 and 22) were given for two or three cycles. RESULTS: Twenty-nine patients with clinical Stages I to IV carcinoma of the cervix with biopsy-proven para-aortic lymph nodes were enrolled in this study. Hyperfractionated external radiotherapy was completed in 86% (25 of 29). Brachytherapy was given in two applications to 48% (14 of 29), 31% (9 of 29) had one intracavitary application, 14% (4 of 29) had no brachytherapy, one had three applications, and one had five HDR applications. Radiotherapy was completed per protocol in 69%. Three courses of chemotherapy were given to 24% (7 of 29), 72% (21 of 29) received two courses, and one 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%. Radiotherapy toxicity was Grade 1 in 7%, Grade 2 in 34%, Grade 3 in 21%, and Grade 4 in 28%. One Grade 5 toxicity occurred and the patient died from a myocardial infarction from chemotherapy and radiotherapy colitis during her course of therapy. The median follow-up time was 18.9 months. The overall survival estimates were 59% at 1 year and 47% at 2 years. The probability of local-regional failure was 38% at 1 year and 49% at 2 years. The probability of disease failure at any site was 45% at 1 year and 59% at 2 years. CONCLUSION: The results suggest that twice-daily external irradiation to the pelvis and para-aortics with brachytherapy and concurrent chemotherapy resulted in an unacceptably high rate (31%, 9 of 29) of Grade 4 nonhematologic toxicity. One patient died from complications of therapy. Radiotherapy was completed per protocol in 69%. The survival estimates appear no better than standard fractionation radiotherapy without chemotherapy. Additional follow-up is necessary for long-term survival estimates.