phosphorus-radioisotopes and Ovarian-Neoplasms

Topics: Brachytherapy; Chemotherapy, Adjuvant; Female; Humans; Neoplasm Recurrence, Local; Neoplasm Staging; Ovarian Neoplasms; Phosphorus Radioisotopes; Radiopharmaceuticals; Radiotherapy, Adjuvant

Topics: Antineoplastic Combined Chemotherapy Protocols; Chromium Compounds; Combined Modality Therapy; Female; Humans; Injections, Intraperitoneal; Neoplasm Staging; Ovarian Neoplasms; Palliative Care; Phosphates; Phosphorus Radioisotopes; Radiopharmaceuticals; Radiotherapy; Radiotherapy Dosage; Randomized Controlled Trials as Topic; Salvage Therapy; Technetium Tc 99m Sulfur Colloid

Topics: Actuarial Analysis; Antineoplastic Agents; Chemotherapy, Adjuvant; Clinical Trials as Topic; Combined Modality Therapy; Female; Humans; Infusions, Parenteral; Laparotomy; Multicenter Studies as Topic; Neoplasm Recurrence, Local; Ovarian Neoplasms; Phosphorus Radioisotopes; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic; Reoperation; Salvage Therapy; Survival Analysis; Treatment Outcome

Radiation therapy is an effective curative treatment modality in early ovarian cancer. A combination of the independent prognostic factors of grade, stage, and residual disease defines an "intermediate" risk group whose probability of long-term disease-free survival from abdomino-pelvic radiation therapy (APRT) is between 62 and 91%. This group in which abdomino-pelvic radiotherapy is recommended as the sole postoperative treatment is mainly constituted from patients with Stage II disease of all grades with no residuum or less than 2 cm residuum in the pelvis and selected optimal Stage III patients with low grade tumors. No therapy has been shown to benefit patients with Stage I grade 2 or 3 tumors, although relapse risks of 30% justify postoperative treatment in this group. APRT significantly reduced relapse risk in patients with Stages I and II disease, where tumors were densely adherent. The late toxicity of APRT is acceptable. When the abdominal dose is restricted to a total of 25 Gy and the pelvic dose to 45 Gy serious complications occur in less than 4% of patients. 32P, widely utilized in early-stage disease, has not been shown to be beneficial compared to cisplatin in a study of the Norwegian Radium Hospital. Its dosimetry precludes effective dosing of tumor at a depth of more than 1 to 2 mm from the peritoneal surface and of the retroperitoneal nodes. Its use should be abandoned. APRT is an effective anti-tumor modality in ovarian cancer and cannot be discarded. Further studies of this modality are justified. Its future exploitation lies in manipulations to increase the therapeutic ratio by either altered radiotherapy fractionation schemes and/or potential combination with radiation sensitizers.

Topics: Combined Modality Therapy; Disease-Free Survival; Female; Humans; Neoplasm Staging; Ovarian Neoplasms; Phosphorus Radioisotopes; Prognosis; Radiotherapy Dosage; Remission Induction

The optimal treatment of early-stage ovarian borderline tumors is controversial. Only a few randomized trials evaluating adjuvant treatment for this disease have been published. Between 1970 and 1988 four consecutive randomized trials, including patients with ovarian borderline tumors, were conducted at the Norwegian Radium Hospital. After surgery, 253 stage I-II borderline tumors without residual disease were randomly allocated to these protocols. The adjuvant treatment in the four trials consisted of [1] external irradiation (Ext) combined with intraperitoneal instillation of radioactive gold (198Au) or Ext alone, [2] intraperitoneal radioactive therapy followed by thio-TEPA or no further treatment, [3] thio-TEPA or no adjuvant therapy, and [4] cisplatin or 32P treatment. The patients were equally distributed according to prognostic variables within the eight randomization groups. The overall corrected and crude survival were 99 and 94%, respectively. In 83% of the patients a hysterectomy, bilateral salpingo-oophorectomy, and omentectomy was performed. None of the patients with less extensive surgery relapsed. Adjuvant therapy did not seem to improve the overall corrected survival. On the contrary, toxicity was added with small bowel complications after radiation therapy, neurotoxicity after cisplatin treatment, and bone marrow toxicity after thio-TEPA therapy. It is concluded that stage I borderline tumors should not receive any adjuvant treatment.

Topics: Adult; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Female; Humans; Middle Aged; Ovarian Neoplasms; Phosphorus Radioisotopes; Prospective Studies; Radiotherapy; Thiotepa

Intraperitoneal radioactive chromic phosphate was administered to 69 patients with Stage I and II ovarian carcinoma who had undergone comprehensive surgical staging. Intestinal obstruction requiring surgical intervention occurred in four patients and was the most severe complication. Abdominal pain was the most common post-therapy complaint. Attention to time and technique of drug administration could minimize complications.

Topics: Adolescent; Adult; Aged; Chromium; Chromium Compounds; Female; Follow-Up Studies; Humans; Injections, Intraperitoneal; Melphalan; Middle Aged; Ovarian Neoplasms; Phosphates; Phosphorus Radioisotopes; Prospective Studies; Radiotherapy

Though radiocolloids have been used for over twenty years in the treatment of ovarian cancer, no comprehensive review of the literature exists. This review incorporates the historical development of radiocolloids, discusses the physical properties and physics of the two commonly used colloids, radioactive gold (Au-198) and radioactive phosphorus (P-32), discusses instillation and distribution of intraperitoneally administered P-32, and reviews result of treatment. The conclusions reached from this review are that Au-198 is a very different radiocolloid than P-32; that the dose of clinically used P-32 is determined from an empirically determined dose of Au-198; and that the dose of 100 mCi to 150 mCi of Au-198 yields significantly greater radiation than 10 mCi to 15 mCi of P-32. The complications associated with Au-198 are results of a possibly excessive dose, with a significant gamma component, delivered over a shorter period of time. It is clear that in greater than 99% of distintegrations each beta particle is associated with a gamma component. The review of the literature also shows that no propsective randomized well controlled study has indicated the effectiveness of P-32 over other treatment modalities. The clinical applicability of P-32 awaits prospective randomized trials and the ability to accurately determine dose and dose-distribution in-vivo.

Topics: Dose-Response Relationship, Radiation; Female; Gold Radioisotopes; Humans; Ovarian Neoplasms; Phosphorus Radioisotopes

The objectives of this prospective randomized study of consolidation therapy were to evaluate recurrence-free survival (RFS), overall survival (OS), and the morbidity of intraperitoneal (IP) chromic phosphate suspension (32P) therapy in patients with stage III epithelial ovarian carcinoma who have no detectable evidence of disease at the second-look laparotomy (SLL) procedure after primary chemotherapy.. In a multi-institution clinical cooperative trial, 202 eligible patients with a negative SLL were randomly selected to receive either 15 mCi IP 32P (n = 104) or no further therapy (NFT; n = 98).. With a median follow-up of 63 months in living patients, 68 patients in the IP 32P group (65%) and 63 patients in the NFT group (64%) have developed tumor recurrence. The relative risk of recurrence is 0.90 (IP 32P to NFT) (90% confidence interval [CI], 0.68 to 1.19). The 5-year RFS rate is 42% and 36% for the IP 32P and NFT groups, respectively; the difference is not statistically significant (log-rank test, P =.27). There was no statistically significant difference in OS (P =.19). The relative risk of death is 0.85 (IP 32P to NFT) (90% CI, 0.62 to 1.16). Sixteen patients (8%) experienced grade 3 or 4 adverse effects, with eight in each respective group.. Intraperitoneal chromic phosphate did not decrease the risk of relapse or improve survival for patients with stage III epithelial ovarian cancer after a negative SLL. Despite complete pathologic remission at SLL after initial surgery and platinum-based chemotherapy, 61% of stage III ovarian cancer patients had tumor recurrence within 5 years of negative SLL. This indicates a need for more effective initial therapy and further studies of consolidation therapy.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma; Chi-Square Distribution; Chromium Compounds; Combined Modality Therapy; Female; Humans; Infusions, Parenteral; Laparotomy; Middle Aged; Neoplasm Recurrence, Local; Ovarian Neoplasms; Phosphates; Phosphorus Radioisotopes; Proportional Hazards Models; Prospective Studies; Survival Analysis; Treatment Outcome

To conduct a prospective study of intraperitoneal radioactive chromic phosphate (32P) versus cyclophosphamide-cisplatin (CP) in women with early ovarian cancer at high risk for recurrence (International Federation of Gynecology and Obstetrics stage Ia or Ib grade 3 or Ic or stage II, no macroscopic residual disease) and to compare cumulative incidence of recurrence, overall survival, and relative toxicity.. A total of 251 patients were randomly assigned to treatment with 32P or CP. Twenty-two (8.7%) were ineligible following centralized pathology review. Of the 229 patients included in the analysis, 110 received 32P, and 119 received CP.. The cumulative incidence of recurrence at 10 years was 35% (95% CI, 27% to 45%) for patients receiving 32P and 28% (95% CI, 21% to 38%) for those receiving CP. Patients receiving CP had a recurrence rate 29% lower than that of those receiving 32P (P =.15, two-tail test). The death rate for patients treated with CP was 17% lower than that for patients treated with 32P (difference not significant). Combining both arms, the 10-year cumulative incidence of recurrence for all stage I patients was 27% (95% CI, 20% to 34%) compared with 44% (95% CI, 32% to 56%) for stage II patients (P =.01). Both regimens were reasonably well tolerated, but problems with inadequate distribution (7%) and small-bowel perforation (3%) make the otherwise less toxic 32P less acceptable.. Although there are no statistically significant differences in survival, the lower cumulative recurrence seen with CP and complications of 32P administration make platinum-based combinations the preferred adjuvant therapy for early ovarian cancer patients at high-risk for recurrence.

Topics: Adenocarcinoma, Mucinous; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Endometrioid; Chemotherapy, Adjuvant; Chromium Compounds; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Cystadenocarcinoma, Serous; Disease-Free Survival; Female; Humans; Injections, Intraperitoneal; Middle Aged; Neoplasm Recurrence, Local; Ovarian Neoplasms; Phosphates; Phosphorus Radioisotopes; Prospective Studies; Survival Rate; Treatment Outcome

The purpose of this study was to evaluate the efficacy of adjuvant 32P for patients with high-risk, early-stage ovarian carcinoma. Twenty-five patients underwent apparent complete resection followed by 32P (15 mCi) at the University of Florida between 1976 and 1993. Minimum and median follow-up times were 3 and 8 years, respectively. The rate of local control at 10 years was 83%. Four of the 5 patients who experienced recurrent disease had a component of intra-abdominal disease at the time of relapse. The absolute and cause-specific survival rates at 10 years were 68% and 82%, respectively. There were no severe acute complications. Five patients experienced significant late complications, including chronic abdominal cramping that was treated conservatively (3 patients) and small bowel obstruction necessitating surgical intervention (2 patients). Adjuvant 32P results in disease control and survival rates that are similar to those observed after adjuvant chemotherapy. However, the risk of late complications, particularly small bowel obstruction, is higher.

Topics: Adult; Aged; Aged, 80 and over; Disease-Free Survival; Female; Follow-Up Studies; Humans; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Ovarian Neoplasms; Phosphorus Radioisotopes; Prognosis; Radiotherapy, Adjuvant; Survival Rate

This study addressed the technique of intraperitoneal distribution imaging (IDI). A literature search (MEDLINE database) revealed wide variations in IDI techniques without a basis for comparison. From April 1990 to September 1992, the authors studied 8 patients (age 43-65 years) with ovarian cancer. A total of 1000 ml of normal saline and 1 mCi of Tc-99m SC was infused intraperitoneally for IDI. In one patient loculation was observed, but only 250 ml of normal saline was infused with Tc-99m SC. A repeat study using our standard technique rendered free intraperitoneal distribution in this patient, as well as in the other seven cases. Some investigators recommend low volumes, but in our experience this produced the finding of pseudoloculation, which could change treatment inappropriately. Although the number of patients studied at our institution was small, administration of 1 liter intraperitoneally provided consistent IDI results.

Topics: Chromium Compounds; Female; Humans; Infusions, Parenteral; Middle Aged; Ovarian Neoplasms; Peritoneal Cavity; Phosphates; Phosphorus Radioisotopes; Radionuclide Imaging; Sodium Chloride; Technetium Tc 99m Sulfur Colloid; Tissue Distribution

The optimal treatment of early-stage ovarian borderline tumors is controversial. Only a few randomized trials evaluating adjuvant treatment for this disease have been published. Between 1970 and 1988 four consecutive randomized trials, including patients with ovarian borderline tumors, were conducted at the Norwegian Radium Hospital. After surgery, 253 stage I-II borderline tumors without residual disease were randomly allocated to these protocols. The adjuvant treatment in the four trials consisted of [1] external irradiation (Ext) combined with intraperitoneal instillation of radioactive gold (198Au) or Ext alone, [2] intraperitoneal radioactive therapy followed by thio-TEPA or no further treatment, [3] thio-TEPA or no adjuvant therapy, and [4] cisplatin or 32P treatment. The patients were equally distributed according to prognostic variables within the eight randomization groups. The overall corrected and crude survival were 99 and 94%, respectively. In 83% of the patients a hysterectomy, bilateral salpingo-oophorectomy, and omentectomy was performed. None of the patients with less extensive surgery relapsed. Adjuvant therapy did not seem to improve the overall corrected survival. On the contrary, toxicity was added with small bowel complications after radiation therapy, neurotoxicity after cisplatin treatment, and bone marrow toxicity after thio-TEPA therapy. It is concluded that stage I borderline tumors should not receive any adjuvant treatment.

Topics: Adult; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Female; Humans; Middle Aged; Ovarian Neoplasms; Phosphorus Radioisotopes; Prospective Studies; Radiotherapy; Thiotepa

The appropriate therapy for patients with localized (FIGO Stage I and II) ovarian cancer has been poorly defined for all age groups and particularly for the elderly. Few prospective randomized comparisons of adjuvant therapy after careful surgical staging have been performed. The Gynecologic Oncology Group (GOG) has performed a series of trials testing adjuvant treatment in carefully staged patients with early-stage ovarian cancer. Early trials included few elderly patients but the most recent trial (GOG 95) included 18% over the age of 65 years.. Comprehensive surgical staging defined by protocol is performed before randomization. Patients with predefined stages and histologies are included and the patients are randomized prospectively to receive either intraperitoneal phosphorus-32 or three monthly cycles of cyclophosphamide and cisplatin. Assessment of the value of this adjuvant therapy will depend on survival, disease-free survival, and relapse pattern differences between the two adjuvant therapies.. This is an ongoing clinical trial and insufficient numbers of patients have been randomized for definitive conclusions. There have been seven recurrences on both arms of the trial with a median time to recurrence of 14 months. There currently are no significant age differences between relapsed patients and disease-free patients. At this point, 12 elderly patients have been randomized to each of the arms of therapy.. Although no apparent survival differences exist for elderly patients in the most recent adjuvant chemotherapy trial of early ovarian cancer, the number of patients with cancer randomized and follow-up are insufficient to establish such a difference. Currently there is no evidence that elderly patients display a significant difference in relapse frequency or pattern.

Topics: Adult; Aged; Aged, 80 and over; Aging; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cyclophosphamide; Female; Humans; Melphalan; Middle Aged; Neoplasm Staging; Ovarian Neoplasms; Phosphorus Radioisotopes; Prospective Studies

Intraperitoneal radioactive phosphorus (phosphorus-32) has been used in ovarian cancer during the last three decades. In the current study, the survival results, the patterns of recurrence, morbidity rates, and phosphorus-32 distribution scintigrams were reviewed in 313 patients treated with phosphorus-32 colloid.. Between July 1982 and July 1988, 245 patients with epithelial ovarian carcinoma were treated with phosphorus-32 as primary adjuvant treatment; 59 patients received phosphorus-32 as consolidating therapy after negative results during second-look surgery and 9, after positive findings during second-look laparotomy. Fifty patients with negative second-look findings were assigned randomly to receive phosphorus-32 or no treatment. The phosphorus-32 distribution was studied by scintigraphic imaging in 297 patients.. The actuarial 5-year crude survival rate was 81% in the group treated with phosphorus-32 adjuvantly and 79% in the group treated after second-look surgery. Crude and disease-free survival rates were similar in both groups randomized at second-look surgery to receive either phosphorus-32 or no treatment. Phosphorus-32 scintigraphy showed major isotopic accumulations in 48 (16%) patients. There were two deaths (0.6%), which, at least partly, could be attributed to the phosphorus-32 treatment. Small bowel obstruction without tumor recurrence occurred in 22 (7%) patients (13 treated surgically and 9 medically) and was not related to any patient characteristic, including phosphorus-32 distribution.. Phosphorus-32 therapy was associated with a considerable number of bowel complications. The occurrence of small bowel obstruction could not be predicted by any patient characteristic. Without an untreated observation group, the authors were unsure whether adjuvant phosphorus-32 treatment conferred a survival advantage.

Topics: Colloids; Combined Modality Therapy; Female; Humans; Injections, Intraperitoneal; Laparotomy; Middle Aged; Neoplasm Staging; Ovarian Neoplasms; Phosphorus Radioisotopes; Prospective Studies; Radionuclide Imaging; Survival Analysis; Tissue Distribution

Thirty-four patients with epithelial carcinoma of the ovary were entered into a trial of adjuvant intraperitoneal P-32 following induction chemotherapy and a negative second-look laparotomy. The breakdown by initial Stage was Stage IC, 5; Stage II, 3; Stage III optimal, 22; and Stage III suboptimal, 4. Previous treatment consisted of 4-12 cycles (median 6) of cisplatin or carboplatin-based combination chemotherapy. Fifteen millicuries of P-32 were instilled via a Tenckhoff catheter placed at the time of second-look laparotomy. Because of a 22% incidence of bowel injury in the first 23 patients, the P-32 dose was reduced to 12 mCi in the last 11 patients. To date, there have been no bowel injuries at the lower dose. Eighteen of the 34 (53%) patients have relapsed with a median time to relapse of 20 months and a median follow-up for all patients of 31 months. There has been no difference in the relapse rate between a dose of 12 and 15 mCi. Intraperitoneal P-32 does not appear to reduce the relapse rate following a negative second-look laparotomy. The incidence of bowel injury is dose dependent and is higher than that seen in patients treated as an adjuvant following initial surgery without subsequent chemotherapy or second-look laparotomy.

Topics: Adult; Aged; Brachytherapy; Carcinoma; Chromium; Chromium Compounds; Combined Modality Therapy; Dose-Response Relationship, Radiation; Female; Humans; Intestines; Life Tables; Middle Aged; Neoplasm Staging; Ovarian Neoplasms; Peritoneal Cavity; Phosphates; Phosphorus Radioisotopes; Radiation Injuries; Reoperation; Survival Analysis

In this study, 347 patients with epithelial ovarian cancer without residual tumor after primary laparotomy, were assigned randomly to receive either intraperitoneal instillation of radioactive phosphorus (32P) or six courses of cisplatin (50 mg/m2). Patients randomized to receive 32P with extensive intraperitoneal adhesions were treated with whole-abdomen irradiation instead of 32P (n = 28). The median follow-up was 62 months. Crude and disease-free survival were similar in all groups. Late bowel complications occurred more often in patients treated with 32P compared with the cisplatin group. The estimated 5-year crude survival rate was as high as 95% in patients with borderline or well-differentiated tumors in Stage I. It is suggested that these patients can be treated adequately by operation alone. Patients with moderately or poorly differentiated cancers in Stage I disease had a 5-year crude survival rate of 75%. In these patients, the relapse risk was high enough to warrant postoperative treatment. The efficacy of adjuvant treatment in this subgroup of patients can only be established in a prospective randomized study comparing postoperative adjuvant treatment with a no-treatment arm. Because of the high number of late bowel complications after 32P treatment, it was recommended that cisplatin be used as standard adjuvant treatment for subsequent controlled studies.

Topics: Cisplatin; Combined Modality Therapy; Female; Follow-Up Studies; Humans; Middle Aged; Neoplasm Staging; Ovarian Neoplasms; Phosphorus Radioisotopes; Recurrence

Intraperitoneal radioactive chromic phosphate was administered to 69 patients with Stage I and II ovarian carcinoma who had undergone comprehensive surgical staging. Intestinal obstruction requiring surgical intervention occurred in four patients and was the most severe complication. Abdominal pain was the most common post-therapy complaint. Attention to time and technique of drug administration could minimize complications.

Topics: Adolescent; Adult; Aged; Chromium; Chromium Compounds; Female; Follow-Up Studies; Humans; Injections, Intraperitoneal; Melphalan; Middle Aged; Ovarian Neoplasms; Phosphates; Phosphorus Radioisotopes; Prospective Studies; Radiotherapy

About a third of patients with ovarian cancer present with localized disease; despite surgical resection, up to half the tumors recur. Since it has not been established whether adjuvant treatment can benefit such patients, we conducted two prospective, randomized national cooperative trials of adjuvant therapy in patients with localized ovarian carcinoma (International Federation of Gynecology and Obstetrics Stages Ia to IIc). All patients underwent surgical resection plus comprehensive staging and, 18 months later, surgical re-exploration. In the first trial, 81 patients with well-differentiated or moderately well differentiated cancers confined to the ovaries (Stages Iai and Ibi) were assigned to receive either no chemotherapy or melphalan (0.2 mg per kilogram of body weight per day for five days, repeated every four to six weeks for up to 12 cycles). After a median follow-up of more than six years, there were no significant differences between the patients given no chemotherapy and those treated with melphalan with respect to either five-year disease-free survival (91 vs. 98 percent; P = 0.41) or overall survival (94 vs. 98 percent; P = 0.43). In the second trial, 141 patients with poorly differentiated Stage I tumors or with cancer outside the ovaries but limited to the pelvis (Stage II) were randomly assigned to treatment with either melphalan (in the same regimen as above) or a single intraperitoneal dose of 32P (15 mCi) at the time of surgery. In this trial (median follow-up, greater than 6 years) the outcomes for the two treatment groups were similar with respect to five-year disease-free survival (80 percent in both groups) and overall survival (81 percent with melphalan vs. 78 percent with 32P; P = 0.48). We conclude that in patients with localized ovarian cancer, comprehensive staging at the time of surgical resection can serve to identify those patients (as defined by the first trial) who can be followed without adjuvant chemotherapy. The remaining patients with localized ovarian cancer should receive adjuvant therapy, and with adjuvant melphalan or intraperitoneal 32P should have a five-year disease-free survival of about 80 percent.

Topics: Adult; Combined Modality Therapy; Female; Humans; Melphalan; Neoplasm Staging; Ovarian Neoplasms; Phosphorus Radioisotopes; Prognosis; Prospective Studies; Randomized Controlled Trials as Topic

Two hundred fifty-seven eligible patients with stage I, IIA "high risk" ovarian carcinoma and IIB, IIIO (disease confined to pelvis), were randomized to either total abdominal radiotherapy (arm A) 2,250 rad in 20 fractions (107 patients), melphalan (arm B) 8 mg/m2/d X 4 every 4 weeks X 18 courses (106 patients), or intraperitoneal chromic phosphate (arm C) 10 to 20 mCi (44 patients). All patients were initially treated with pelvic radiotherapy; arm A, 2,250 rad in ten fractions; and arms B and C, 4,500 rad in 20 fractions. Entry to arm C was discontinued early because of toxicity. In a multifactor analysis using proportional hazards models, no significant difference in survival was observed although there was a marginally significant difference in disease-free survival (P = .015) with arm B being superior to arm A. Stage (P less than .0001), grade (P less than .0001), and histology (P less than .008) were predictors of survival in the multifactor analysis. Performance status, age, and residual disease were significant predictors in the single factor analysis but were not predictive when correction was made for the effects of stage, grade, and histology. Five-year survival rates are 62% for arm A, 61% for arm B, and 66% for arm C. Median duration of follow-up is 8 years. Long-term complications of radiotherapy were seen in 19 patients on arm A, 11 on arm B, and 11 on arm C. Four patients who had received melphalan developed either a myelodysplastic syndrome or acute leukemia. Violations in covering the whole abdominal target volume were correlated with survival.

Topics: Chromium; Chromium Compounds; Clinical Trials as Topic; Combined Modality Therapy; Female; Humans; Melphalan; Ovarian Neoplasms; Phosphates; Phosphorus Radioisotopes; Prognosis; Random Allocation

As part of a randomized trial evaluating several treatment programs in the management of poor prognosis, early stage ovarian cancer, 53 patients were randomized to receive a combination of pelvic external beam radiation, 4000 rad plus 10-20 millicuries of radioactive chromic phosphate given intraperitoneally. Only 35 patients (66%) actually received the chromic phosphate. The other 18 did not enter this phase of treatment for a variety of reasons documented in this report. Ten (29%) of the 35 patients receiving the full course of treatment had significant long term side effects with the median time to onset of symptom being 9 months after the chronic phosphate was given. There were no treatment-related deaths. The complications could not be related to the dose of the isotope, the technique of administration, nor any other definable predisposing factors. This combination is not recommended for further study.

Topics: Brachytherapy; Chromium; Chromium Compounds; Female; Humans; Melphalan; Ovarian Neoplasms; Phosphates; Phosphorus Radioisotopes

A multimodality treatment program has been applied to ovarian carcinoma at the Johns Hopkins Hospital since August 1975. Forty-nine patients were subdivided into 23 patients with maximally resected Stage III micrometastatic, and 26 patients with significant retained disease, 20 with Stage III macrometastatic and 6 with Stage IV. After initial pilot studies, those patients with minimally retained disease entered a randomized prospective study. Antiovarian antiserum was used in one arm of the study; in both study arms colloidal P-32, delayed split whole abdominal irradiation, and maintenance melphalan were used. For the 23 patients with micrometastatic disease the cumulative survival and survival without evidence of disease at four years is 78 and 34% respectively. Twenty-six patients with macrometastatic disease were treated with or without intraperitoneal antiserum and multiagent chemotherapy; their cumulative one year survival is 50%. The lack of significant toxicity of intraperitoneal antiovarian antiserum and the results of multimodality therapy indicate the feasibility of this therapeutic approach to further improve ovarian cancer therapy.

Topics: Adenocarcinoma, Mucinous; Altretamine; Antibodies, Neoplasm; Carcinoma; Cisplatin; Clinical Trials as Topic; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Female; Humans; Melphalan; Ovarian Neoplasms; Ovary; Phosphorus Radioisotopes; Prospective Studies; Random Allocation

Topics: Antigens, Neoplasm; Carcinoembryonic Antigen; Drug Therapy, Combination; Female; Humans; Immune Sera; Male; Melphalan; Neoplasm Staging; Ovarian Neoplasms; Peritoneal Neoplasms; Phosphorus Radioisotopes; Radiotherapy Dosage

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Clinical Trials, Phase III as Topic; Cyclophosphamide; Female; Humans; Neoplasm Recurrence, Local; Ovarian Neoplasms; Phosphorus Radioisotopes

Imaging modalities to evaluate ovarian/fallopian tube cancer patients for recurrence are limited. Positron emission tomography (PET), computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound lack the sensitivity to consistently detect recurrence or measurable disease in these patients. A new technique combines PET and CT (PET/CT) images to identify increased metabolic activity and to locate that signal with improved anatomic specificity. The objective of this study is to compare PET/CT, CT, and histologic findings in patients with recurrent ovarian/fallopian tube cancers.. Retrospective chart review of eight patients with primary ovarian (n = 6) or fallopian tube (n = 2) cancer was performed. All eight patients underwent initial cytoreductive surgery. Five patients initially received chemotherapy, one received radioactive phosphorus ((32)P), one received tamoxifen, and one received no therapy. Seven of eight patients had a suspected recurrence based on clinical examination, elevated CA-125 level, and/or abnormal CT findings; one patient requested a PET/CT. Histologic findings from surgery were correlated with PET/CT and CT findings.. All eight patients had positive histology, and of these, seven patients had a negative CT and five patients had lesions that were correctly identified by PET/CT.. Five of the eight (62%) patients had recurrent disease based on correlative histology with a positive PET/CT and a negative CT. These preliminary findings suggest that combined PET/CT may be an effective means of identifying patients with recurrent ovarian/fallopian tube cancer. Such patients could potentially proceed to salvage treatment and avoid the morbidity and expense of surgical assessment. Pilot studies comparing CT, PET, PET/CT, and histologic findings are underway.

Topics: Aged; Fallopian Tube Neoplasms; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Ovarian Neoplasms; Phosphorus Radioisotopes; Retrospective Studies; Risk Factors; Tomography, Emission-Computed; Tomography, X-Ray Computed

We report our experience with consolidative 32P after second-look laparotomy. Forty-three patients received consolidative 32P after platinum-based chemotherapy and a negative (39 patients, 91%) or positive (4 patients) second-look laparotomy. Thirty-one patients (72%) initially had stage III (30 patients) or stage IV (1 patient) disease; 28 patients (65%) had grade 3 tumors. Patients had follow-up from 3.5 to 14.9 years (median, 7.7 years); no patient was lost to follow-up. The 5-year rates of control of disease within the abdomen (local control) for the overall group and the subset of patients with stage II-IV disease and a negative second-look laparotomy were 65% and 69%, respectively. The corresponding 5-year survival rates were 78 and 81%, respectively. Multivariate analyses revealed that tumor found at second-look laparotomy significantly influenced the likelihood of local control and cause-specific survival. Acute side effects included cellulitis (1 patient) and ileus (3 patients). Two patients (5%) experienced severe late complications; both experienced small bowel obstruction that necessitated surgical intervention. Consolidative 32P appears to reduce the risk of recurrence and improve survival after negative second-look laparotomy. The risk of significant complications is low.

Topics: Antineoplastic Agents; Female; Humans; Laparotomy; Ovarian Neoplasms; Phosphorus Radioisotopes; Recurrence; Reoperation

A patient with postoperative Stage I ovarian carcinoma received 15 mCi of 32P-chromic phosphate suspension in normal saline intraperitoneally as part of her therapy. The following day, a portion of the infused radiopharmaceutical and normal saline had passed transdiaphragmatically into the patient's right pleural cavity. Thoracentesis removed as much fluid as possible and this fluid contained radioactive material. In the ensuing 4 yr, the patient has not manifested any detectable pleural or pulmonary abnormalities attributable to the radioactivity. Retrospective review of 100 consecutive patients receiving 32P-chromic phosphate intraperitoneal therapy resulted in 43 patients in whom the hemithoraces could be evaluated scintigraphically. Three of the 43 patients (7%) had right pleural fluid radioactivity. This is similar to the percentages reported in patients with cirrhosis with ascites in whom hepatic hydrothorax is identified.

Topics: Chromium Compounds; Extravasation of Diagnostic and Therapeutic Materials; Female; Humans; Infusions, Parenteral; Middle Aged; Ovarian Neoplasms; Peritoneal Cavity; Phosphates; Phosphorus Radioisotopes; Pleura; Pleural Effusion; Technetium Tc 99m Sulfur Colloid; Time Factors; Tissue Distribution

Trends in CA-125 levels after completion of therapy in ovarian cancer patients who received intraperitoneal radioactive chromic phosphate therapy (32P) after primary surgical resection or second-look surgery were evaluated. Ninety patients who underwent surgical exploration and 32P were reviewed. Twenty-nine patients were excluded due to insufficient number of CA-125 levels or recurrence within 12 months, with 61 patients with serial CA-125 levels and no evidence of disease for 12 months available for analysis. 32P followed initial resection in 24 patients (16 Stage I, 3 Stage II, 5 Stage III). 32P followed chemotherapy and second-look procedures in 37 patients (4 Stage I, 3 Stage II, 27 Stage III, 3 Stage IV). Elevated CA-125 levels were present in 25 (41%) patients within 12 months of 32P (46% after primary exploration, 38% after second-look). The degree of CA-125 elevation (U/ml) was 30-100 (23%), 100-200 (11%), and >200 (7%). Of the 25 patients with an elevated CA-125, the elevation persisted more than 4 months in 11 (44%). All but two patients had normal CA-125 levels by 12 months. An abnormal elevation in CA-125 was seen in 33% of patients 4 months after receiving 32P and abdominal surgery, with values ranging as high as 500 U/ml. Although elevations in CA-125 are reported following surgery alone, the duration of elevation appears to be longer with 32P. Therefore, persistent elevations of CA-125 following 32P between 4 and 12 months should be judged with caution as they may not reflect recurrent disease.

Topics: CA-125 Antigen; Chromium Compounds; Female; Humans; Injections, Intraperitoneal; Ovarian Neoplasms; Phosphates; Phosphorus Radioisotopes; Postoperative Period; Reoperation; Retrospective Studies

The use of radioactive colloidal phosphorus 32 (32P) in the treatment of epithelial ovarian cancer continues to be controversial. One institution's experience with the use of 32P in 30 patients with epithelial ovarian cancer was reviewed retrospectively. One hundred percent of attempts at placement of 32P intra-abdominally were ultimately successful. The complication rate was 11%. Mean clinical (asymptomatic) disease-free survival in patients with stage III ovarian cancer was as follows: 26 months based on absence of disease at reassessment surgery; 26 months based on microscopic residuum; and 30 months based on minimal (< 5 mm) residuum. Mean disease-free survival in patients with early-stage (stages IC through IIC) ovarian cancer was 66 months.

Topics: Brachytherapy; Disease-Free Survival; Female; Humans; Neoplasm Staging; Ovarian Neoplasms; Phosphorus Radioisotopes; Retrospective Studies

For many years, 32P-chromic phosphate (32P-CP) intraperitoneal instillations and platinum analogue chemotherapy have been used to treat disseminated ovarian cancer. To investigate possible enhancement of 32P-CP irradiation due to the concomitant administration of chemotherapy, in vitro studies were undertaken. Based on those laboratory investigations, a clinical regimen of combined 32P-CP and platinum analogue chemotherapy was developed.. In vitro enhancement of 32P-CP cytotoxicity by cisplatin was studied in cultured human ovarian adenocarcinoma (CHOA) cell lines and in a fibroblast cell strain. In addition, ovarian cancer cells obtained from the malignant abdominal ascites and pleural effusions of 10 individual patients were also studied ex vivo. As part of routine clinical care, 30 patients with disseminated ovarian adenocarcinoma underwent up to eight monthly cycles of platinum analogue chemotherapy with concomitant intraperitoneal instillation of 5 mCi of 32P-CP at each monthly chemotherapy cycle.. There was an enhanced and possibly supra-additive effect of cisplatin on the cytotoxicity from 32P-CP irradiation. For the 30 patients, the survival rate at 3 yr was 63%.. Phosphorus-32 CP low-dose intraperitoneal treatments in conjunction with platinum analogue chemotherapy is a promising approach for the treatment of disseminated intraperitoneal ovarian cancer.

Topics: Adenocarcinoma; Cell Survival; Chromium Compounds; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Female; Humans; Ovarian Neoplasms; Phosphates; Phosphorus Radioisotopes; Radiotherapy Dosage; Survival Rate; Tumor Cells, Cultured

Women diagnosed with early stage ovarian cancer may be considered for adjuvant therapy. Intraperitoneal chromic phosphate (P-32) is commonly used in these patients with few complications. A woman found to have early stage ovarian cancer was given intraperitoneal P-32 in the presence of a lingering pelvic infection, which is usually not mentioned as a contraindication to its use. Radiation damage to the small bowel and cecum developed as did damage to the ureter and bladder, which then required surgery.

Topics: Adult; Chromium Compounds; Contraindications; Cystadenoma, Mucinous; Female; Humans; Hysterectomy; Instillation, Drug; Ovarian Neoplasms; Pelvic Inflammatory Disease; Peritoneal Cavity; Phosphates; Phosphorus Radioisotopes; Radiation Injuries; Radiotherapy, Adjuvant

From 1982 through 1989, 56 patients with Stage III epithelial carcinoma of the ovary received intraperitoneal chromic phosphate following chemotherapy and second look (52 pts) or as the only postsurgical management (4 pts). Median follow-up was 48 months (range of 24 to 108 months). The 4 patients treated following primary surgery with P-32 without chemotherapy had microscopic abdominal disease (3 pts) or complete reduction of gross abdominal disease (1 pt), and their 5-year survival was 100%. Of the 52 patients treated with P-32 following PAC chemotherapy, 23 were pathologic negative, 15 had microscopic residual, and 14 had gross residual at second look. The 5-year survival following second look was 75% for negative, 48% for microscopic, and 32% for gross residual. There were 4 Grade 3 GI complications (7%). There were no complications in the 38 patients who received the P-32 within 12 hr of surgery. The use of P-32 as an adjuvant for Stage I and II epithelial carcinoma of ovary has been found to be effective in prior GOG trials. We have expanded the selection criteria in patients with Stage III carcinoma to include those who can be surgically reduced to microscopic residual at primary surgery or second look following chemo reduction. Because of multiple prognostic variables affecting survival in Stage III ovarian cancer, a randomized study with control arm would be necessary to draw firm conclusions regarding the effectiveness of P-32. The 5-year survival in this group of patients compares favorably to published reports.

Topics: Adult; Carcinoma; Combined Modality Therapy; Female; Follow-Up Studies; Humans; Infusions, Parenteral; Middle Aged; Multivariate Analysis; Neoplasm Staging; Ovarian Neoplasms; Phosphorus Radioisotopes; Prognosis; Reoperation; Retrospective Studies; Survival Rate

Intraperitoneal (IP) radioactive chromic phosphate (P32) remains investigational in the treatment of patients with ovarian and/or endometrial cancer. Single-use percutaneously placed catheters offer the advantage of therapy without additional surgery.. Between August, 1986 and October, 1992, 25 patients underwent bedside percutaneous catheter placement under local anesthesia without ultrasonographic or radiologic guidance, using a specialized central venous catheter.. Catheter insertion was successful in 22 of 25 patients (88%) with good IP distribution. Of these, 18 of 22 patients (82%) underwent successful catheter placement with one attempt and 4 of 22 (18%) after one to three additional attempts. The technical failure rate was 12%. Multiple catheter placement attempts were associated with an increased incidence of complications (r = 0.63). Bowel entry occurred in 4 of 25 patients (16%) during 5 of 43 attempts at catheter placement (12%) but was without clinical sequelae. The likelihood of bowel entry significantly increased with more than two attempts (P = 0.02). A median of 39 days (range, 7-156 days) elapsed between the preceding laparotomy and catheter insertion.. Percutaneous catheter placement is successful and well tolerated in the majority of patients and should be considered for patients receiving IP P32.

Topics: Adult; Aged; Catheterization; Catheterization, Central Venous; Chromium Compounds; Disposable Equipment; Endometrial Neoplasms; Female; Humans; Middle Aged; Ovarian Neoplasms; Phosphates; Phosphorus Radioisotopes; Retrospective Studies

Topics: Female; Humans; Lymphatic Metastasis; Neoplasm Recurrence, Local; Ovarian Neoplasms; Phosphorus Radioisotopes

Peritoneal seeding remains a prominent failure pattern in patients with invasive epithelial ovarian cancer, even following a pathologically negative second-look laparotomy (2LL). In an attempt to decrease the risk of peritoneal recurrence, we have treated patients with no clinical or histopathologic evidence of disease at 2LL with 15 mCi of chromic phosphate suspension intraperitoneally (32P).. Between 1973-1987, 69 patients with stages I-III invasive epithelial ovarian cancer in complete clinical remission were found to have no evidence of disease at 2LL. Fifty-one patients received intraperitoneal 32P. Thirty-five patients, otherwise eligible for 32P, did not receive it primarily due to other treatment protocols, peritoneal adhesions, or the recommendation that no further therapy be given following a negative 2LL. Patients in both groups were comparable with regard to stage, histology, grade, median age, residual disease following initial surgery, and chemotherapeutic regimen. The median follow-up for uncensored patients is 58 months (minimum, 18 months).. The 5-year actuarial disease-free survival rate from the date of 2LL was 86% for those receiving 32P and 67% for those not receiving 32P (P = 0.05). The corresponding 5-year overall survival rates were 90 and 78%, again favoring patients treated with 32P.. There were minimal acute side effects from 32P. Late adverse effects were similar in the two groups. Bowel complications were seen in 3 of 51 patients receiving 32P and 1 of 18 patients not receiving 32P.. We have found intraperitoneal 32P administration immediately after 2LL to be a safe and well-tolerated therapy. Our data suggest that 32P confers a survival advantage to patients with a pathologically negative 2LL. These findings suggest a continued role for second-look laparotomy with the use of 32P in selected patients.

Topics: Chi-Square Distribution; Epithelium; Female; Follow-Up Studies; Humans; Infusions, Parenteral; Instillation, Drug; Laparotomy; Ovarian Neoplasms; Peritoneal Neoplasms; Phosphorus Radioisotopes; Regression Analysis; Reoperation; Retrospective Studies; Survival Analysis; Survival Rate

Topics: Brachytherapy; Catheterization; Female; Humans; Intestine, Small; Ovarian Neoplasms; Phosphorus Radioisotopes; Technetium Tc 99m Sulfur Colloid; Tomography, Emission-Computed, Single-Photon

From 1982 through 1989, 94 patients at the University of Louisville with ovarian neoplasm had abdominal instillation of 15 mCi chromic 32P as part of their management. The timing of the 32P was immediately postoperative in 55 patients and delayed greater than 24 hr in 39 patients. This is an analysis of factors contributing to gastrointestinal (GI) complications. GI complications were graded according to RTOG guidelines. There was a total of 11 GI complications grade 3 or worse for an overall incidence of 12%. Factors analyzed include timing of 32P delivery, age, stage, number of previous surgeries, use of Hyskon at surgery, addition of external beam radiation, and subsequent use of chemotherapy. There were significantly fewer complications when 32P was given on the same day as surgery than when 32P administration was delayed more than 12 hr following surgery (4% vs 21%), P = 0.007. This difference held significance when adjusted for the number of previous surgeries, use of Hyskon, external beam radiation, and stage. None of the other factors had a significant effect on complication rate. There have been no incidences of contamination even though 32P instillation in the immediate post-operative period had increased risk of contamination due to wound leakage or reoperation. In our experience, the delivery of 32P in the immediate postoperative period resulted in a significant reduction in abdominal complications.

Topics: Actuarial Analysis; Carcinoma; Female; Humans; Instillation, Drug; Neoplasm Staging; Ovarian Neoplasms; Phosphorus Radioisotopes; Radiation Injuries; Tissue Adhesions

Forty-nine women with apparent Stage I and II ovarian carcinoma received intraperitoneal phosphate 32 as the only adjuvant therapy after primary surgery. In addition to bilateral salpingo-oophorectomy, 40 (82%) had analysis of peritoneal cytology, and 35 (71%) underwent omentectomy. Random peritoneal biopsies and retroperitoneal lymph node sampling were not done in any of these patients. The overall and disease-free survival rates were 86% and 75%, respectively, with no significant differences by stage, histologic grade, histologic type, or low-risk versus high-risk subsets recognized in patients who received comprehensive surgical staging. Seven (58%) of 12 patients had lymph node metastasis as the first site of recurrence, including two of three with late recurrences. Significant morbidity related to intraperitoneal chromic phosphate (32P) occurred in one (2%) woman. These results emphasize the need for comprehensive surgical staging of women with apparent early ovarian carcinoma to aid in the selection of appropriate initial adjuvant therapy.

Topics: Chromium; Chromium Compounds; Combined Modality Therapy; Female; Humans; Infusions, Parenteral; Neoplasm Staging; Ovarian Neoplasms; Phosphates; Phosphorus Radioisotopes; Retrospective Studies; Survival Analysis

Thirty-one patients underwent a negative second-look laparotomy between 1976 and 1986. Fourteen patients received intraperitoneal chromic phosphate (P-32) after a negative second-look laparotomy. There has been no local recurrence (zero of 14) and no deaths attributable to recurrent disease. Local control and disease-free survival are 100%, with a minimum follow-up of 2 years and a mean follow-up of 4 years. Seventeen patients received no further therapy because of patient refusal, poor diffusion, or other contraindications to P-32 installation. Four of 17 patients undergoing negative second-look procedures without the addition of P-32 have subsequently recurred. This difference is highly suggestive (P = .076). There have been no major complications with the addition of P-32. The use of intraperitoneal P-32 after negative second-look laparotomies on ovarian carcinoma is well tolerated and effective in preventing recurrence.

Topics: Female; Follow-Up Studies; Humans; Infusions, Parenteral; Laparotomy; Neoplasm Recurrence, Local; Ovarian Neoplasms; Phosphorus Radioisotopes; Reoperation

Between March 1977 and December 1985, 59 patients were treated with intraperitoneal chromic phosphate at The University of Alabama Birmingham Hospitals and its affiliates. Twenty-seven patients received primary adjuvant therapy. Thirty-two patients were treated "secondarily" after tumor recurrence or after a "positive" second-look laparotomy. Associated morbidity was noted to be 12% with reoperation required in 7%. Early stage and grade tumors demonstrate a good prognosis. Little, if any, benefit was demonstrated in "secondary" therapy of advanced stage and grade tumors.

Topics: Chromium; Chromium Compounds; Female; Humans; Instillation, Drug; Neoplasm Recurrence, Local; Ovarian Neoplasms; Peritoneal Cavity; Phosphates; Phosphorus Radioisotopes

From 1975 to 1982, 25 evaluable patients with FIGO Stage I ovarian cancer were treated with intraperitoneal chromic phosphate (32P). All patients underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy with (28%) or without (72%) omentectomy, with no other surgical staging procedures prior to referral. Patients were restaged by laparoscopy (inspection of diaphragms, abdomen, and pelvis), biopsy of suspicious lesions, and peritoneal cytologic washings prior to intraperitoneal chromic phosphate therapy. For the 25 patients, the estimated 5- and 10-year recurrence-free rates and the 5- and 10-year survival rates are 84% and 75%, respectively. Excellent 10-year recurrence-free rates were achieved for Stages IA and IC, nonruptured cysts, and Grade I and II tumors. In contrast, very low 10-year survival rates were achieved for patients with Stage IB, ruptured cysts, or Grade III tumors.

Topics: Adenocarcinoma; Adult; Aged; Chromium; Chromium Compounds; Female; Humans; Injections, Intraperitoneal; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Ovarian Neoplasms; Phosphates; Phosphorus Radioisotopes; Prospective Studies; Time Factors

Between 1973 and 1985, 118 patients in clinical remission after initial surgery and postoperative chemotherapy for epithelial ovarian carcinoma underwent second-look laparotomy at the University of North Carolina. No evidence of disease (NED) was found in 57 of these patients; 43 patients received 15 mCi of radioactive chromic phosphate (32P) suspension given intraperitoneally in the immediate postoperative period. In 29 other patients, only microscopic or minimal residual disease (nodules less than 2 cm in size) was found, seven received 32P alone, ten received 32P and further chemotherapy, and 12 received chemotherapy alone. The 4-year postsecond-look survival of the patients with NED at second-look was 89% for those receiving 32P and 67% for those who had not. The respective figures for patients with minimal residual disease at second-look are 59% versus 22%. Irrespective of treatment, a group at high risk for failure after negative second-look laparotomy has been identified; those with an initial International Federation of Gynecology and Obstetrics (FIGO) stage greater than I and histologic grade greater than 1. A comparison of our data with 18 previously published series, indicates that use of postsecond-look intraperitoneal 32P can improve the progression-free interval, and possibly overall survival, of patients with NED or minimal residual disease without adding significant complications.

Topics: Carcinoma; Chromium; Chromium Compounds; Female; Humans; Infusions, Parenteral; Laparotomy; Middle Aged; Ovarian Neoplasms; Phosphates; Phosphorus Radioisotopes; Prognosis; Reoperation

The use of intraperitoneal radioisotopes in the management of women with ovarian cancer is controversial. We analyzed the experience with intraperitoneal chromic phosphate P 32 at our institution, from October 1979 to February 1983, in 22 patients with various stages and grades of ovarian malignancy. Survival in stage I is 87.5% and in stage II, 50%. Survival is 88.9% among patients with grade 1 tumors and 33.3% for those with grade 3 lesions. Morbidity related to chromic phosphate P 32 was minimal; small bowel obstruction occurred in only one patient who had also received external pelvic irradiation. Our results suggest that chromic phosphate P 32 is a safe, well tolerated, inexpensive, and effective adjuvant to surgery in the management of selected patients with ovarian malignancy.

Topics: Adenocarcinoma; Brachytherapy; Chromium; Chromium Compounds; Cystadenocarcinoma; Endometriosis; Female; Humans; Middle Aged; Ovarian Neoplasms; Phosphates; Phosphorus Radioisotopes

From 1977 through 1984, 23 patients with persistent epithelial carcinomas of the ovary received intraperitoneal instillation with chromic phosphate P 32 suspension as salvage therapy after second- or third-look laparotomy. Patients received a median 10 cycles of chemotherapy before chromic phosphate P 32. Disease consisted of microscopic residual only in 10 patients (43%), macroscopic residual that was completely resected in eight (35%), and macroscopic residual disease in which the largest diameter was less than 0.5 cm in five patients (22%). Ten patients are free of disease at 13 to 94 months after chromic phosphate P 32 salvage therapy. Life table survival is 75% at 2 years and 57% at 4 years, with a disease-free survival rate of 54% at 2 years and 27% at 4 years. Patients with no gross residual disease had median disease-free survival of 27 months versus 9 months for patients with macroscopic residual disease (p greater than 0.1). Only three patients (13%) developed surgical bowel complications related to chromic phosphate P 32. Compared with previous studies, intraperitoneal chromic phosphate P 32 as salvage therapy for patients with minimal residual ovarian carcinoma defined at secondary surgical evaluation results in comparable survival and fewer complications than does salvage abdominopelvic irradiation and should be considered as an option to further chemotherapy in selected patients.

Topics: Actuarial Analysis; Antineoplastic Combined Chemotherapy Protocols; Brachytherapy; Carcinoma, Papillary; Chromium; Chromium Compounds; Combined Modality Therapy; Female; Humans; Neoplasm Staging; Ovarian Neoplasms; Peritoneal Cavity; Phosphates; Phosphorus Radioisotopes; Reoperation

Twenty-eight patients with ovarian carcinoma received 555 MBq of labeled chromic phosphate (P-32) intraperitoneally. Indications for treatment included a high-grade tumor, extracapsular involvement, positive cytologic findings, or residual tumor. Fifteen patients (group 1) had stage I, II, or III completely resected tumor; 13 patients (group 2) had microscopic or less than 3-mm lesions at second-look laparotomy following combination chemotherapy. A major complication occurred in one patient; two patients had minor complications. Overall, 24 of 28 patients (85.7%) were alive at 11-77 months; 23 (82.1%) had no evidence of tumor. Fifteen of 15 (100%) group 1 patients and eight of 13 (61.5%) group 2 patients did not have tumor relapse after 30 months and 28 1/2 months, respectively. P-32 was found to be an effective adjuvant treatment in a select group of patients with ovarian carcinoma who were at high risk for intraabdominal recurrence.

Topics: Brachytherapy; Carcinoma; Chromium; Chromium Compounds; Combined Modality Therapy; Female; Follow-Up Studies; Humans; Neoplasm Recurrence, Local; Neoplasm Staging; Ovarian Neoplasms; Phosphates; Phosphorus Radioisotopes; Posture; Radiotherapy Dosage

Topics: Cytodiagnosis; Female; Humans; Intraoperative Care; Ovarian Cysts; Ovarian Neoplasms; Ovary; Phosphorus Radioisotopes; Precancerous Conditions; Radionuclide Imaging

Single photon emission computed tomography (SPECT) has been shown to be of value in estimating the radiation dose to the peritoneum from 32P therapy. Simple dosimetry calculations, assuming uniform irradiation of tissue, indicate that radiation doses of approximately 40 Gy to the peritoneal surface are achieved. However, the images show that the radionuclide distribution is non-uniform, giving rise to radiation dose variations of at least a factor of 10.

Topics: Chromium; Chromium Compounds; Female; Humans; Ovarian Neoplasms; Peritoneal Neoplasms; Peritoneum; Phosphates; Phosphorus Radioisotopes; Radiation Dosage; Tomography, Emission-Computed

A retrospective study of the use of phosphorus-32 in the treatment of 73 cases of ovarian malignancy to evaluate the safety and morbidity is presented. The surgically confirmed major complication rate with P-32 alone was 4 of 54 cases (7.4%). The addition of external radiation raised the surgically confirmed complication rate to 4 of 19 cases (21%) and with the addition of those diagnosed and treated only medically the rate rose to 8 of 19 cases (42%). In Stage I cases, Grades 1 and 2, there was only 1 death in 26 patients (96%), whereas for Grade 3 tumors only 6 of 12 patients (50%) were living at the end of 2 years.

Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Ovarian Neoplasms; Phosphorus Radioisotopes; Retrospective Studies; Time Factors

Topics: Carcinoma; Combined Modality Therapy; Female; Gold Radioisotopes; Humans; Ovarian Neoplasms; Peritoneal Cavity; Phosphorus Radioisotopes; Prognosis

Systemic distribution of radioactive colloidal chromic phosphate P 32 after intraperitoneal instillation was studied in 10 patients with ovarian or endometrial malignancies. Seven patients without ascites received chromic phosphate P 32 for positive peritoneal washings, rupture of the capsule of the cyst during operation, or minimal Stage III disease. Three patients received chromic phosphate P 32 for recurrent ascites after multiple abdominal paracenteses. Blood and urine radioactivity measurements were performed at selected intervals. There was a clear statistically significant difference (p less than 0.01) between chromic phosphate P 32 activity levels in whole blood, red blood cells, and plasma in patients with and without ascites.

Topics: Adult; Aged; Ascites; Brachytherapy; Chromium; Chromium Compounds; Female; Humans; Kinetics; Middle Aged; Ovarian Neoplasms; Phosphates; Phosphorus Radioisotopes; Uterine Neoplasms

Topics: Breast Feeding; Chromium; Chromium Compounds; Cystadenocarcinoma; Female; Humans; Infant, Newborn; Milk, Human; Ovarian Neoplasms; Phosphates; Phosphorus Radioisotopes; Radiation Dosage

Topics: Adnexa Uteri; Female; Humans; Ovarian Neoplasms; Phosphorus Radioisotopes; Precancerous Conditions; Radionuclide Imaging; Uterine Neoplasms; Uterus

We compared the therapeutic efficacy of alpha and beta emitting radiocolloids for the treatment of experimental malignant ascites. 211At is an almost pure alpha-emitter. As 211At-tellurium colloid, the dose survival curve is linear and extrapolates through the origin in a manner similar to other high linear energy transfer radiations. Doses of 25 microCi were curative. Less than curative doses showed a graded prolongation of median survival. In cured mice, long term histological changes were seen in thyroid tissue. Acute changes were seen in the gastrointestinal tract as early as 2 hr after radiocolloid administration; these changes reached a plateau at 6 hr and were essentially gone 36 hr later. By comparison, radiocolloids of the beta emitters 32P, 165Dy and 90Y were not curative, but relatively large doses did substantially prolong median survival. The doses for maximal effect were 150 microCi 32P-chromic phosphate, 8000 microCi ++165Dy-ferric hydroxide macroaggregates and 200 microCi 90Y-citrate. The most compelling reason for the increased therapeutic efficacy of 211At-tellurium colloid is the direct and densely ionizing character of the emitted alpha radiations.

Topics: Alpha Particles; Animals; Ascites; Astatine; Colloids; Dysprosium; Electrons; Female; Half-Life; Intestinal Mucosa; Mice; Mice, Inbred C3H; Neoplasm Transplantation; Ovarian Neoplasms; Particle Size; Phosphorus Radioisotopes; Radioisotopes; Thyroid Gland; Yttrium Radioisotopes

Topics: Adult; Aged; Antineoplastic Agents; Chromium; Chromium Compounds; Combined Modality Therapy; Female; Humans; Injections, Intraperitoneal; Middle Aged; Ovarian Neoplasms; Phosphates; Phosphorus Radioisotopes; Prognosis

The whole-body distribution of radioactivity after intraperitoneal instillation of 32P-labelled chromic hydroxide particles has been studied in patients operated for early-stage ovarian cancer. Gamma-camera imaging of the abdominal 32P-distribution revealed that the administration procedure was critical for obtaining a homogeneous plating of the radiocolloids on the serosal surface. Dose calculations based on a uniform distribution of 32P in a capillary layer covering the intraperitoneal surface gave an estimated tissue surface dose of about 30 Gy per 370 MBq of 32P administered. The amount of 32P in peripheral blood increased for seven days after instillation followed by a continuous decrease. Bone marrow concentration was from two to five times as high as that in blood, but the total amounts were too small to give significant radiation doses. Gel chromatography showed that 33% of the activity in blood consisted of high molecular weight material, probably colloids. The remainder of the activity (67%) was attached to material of very low molecular weight, appearing as a consequence of physiological degradation of the colloids.

Topics: Abdomen; Colloids; Female; Humans; Injections, Intraperitoneal; Ovarian Neoplasms; Phosphorus Radioisotopes; Radiation Dosage; Radionuclide Imaging; Thorax; Tissue Distribution

Topics: 19-Iodocholesterol; Adolescent; Adult; Diagnosis, Differential; Female; Humans; Middle Aged; Ovarian Cysts; Ovarian Neoplasms; Ovary; Phosphorus Radioisotopes; Radionuclide Imaging; Technetium; Ultrasonography

Ovarian cancer, currently, is the leading cause of death from malignancies arising in the female genital tract. Investigators and collaborative groups are focusing on this problem in an attempt to improve patient survival. The material reviewed has attempted to gather the data that relate to the use of radioisotopes in the treatment of ovarian cancer. The conclusions reached from this review are: Dose. The initial therapeutic dose of 198Au was empirically determined by Muller. This empirically determined dose was then used to estimate a dose of 32P, based on certain assumptions about these radiocolloids that have been shown to be erroneous. It would appear that the administered dose of 100-150 mCi of 198Au yields a significantly greater tissue dose than 10-15 mCi of 32P. Complications. Complications associated with 198Au are a result of a possibly excessive dose, delivered over a shorter period of time, with a significant gamma component. It is clear that in greater than 99 per cent of disintegrations each beta particle is associated with a gamma component. Distribution, dose distribution, and dose rate. These three critical factors have recently been evaluated for intraperitoneal 32P. It would appear that distribution is non-uniform, and thus dose distribution is not homogeneous, and that dose rate is low and may be ineffective in controlling ovarian cancer. Results of treatment. It would appear from a review of the literature that no prospective randomized well-controlled study as indicated the effectiveness of 32P over other treatment modalities. There is only circumstantial evidence for its effectiveness. The clinical applicability of 32P in the treatment of Stage I ovarian cancer, as part of a treatment protocol, awaits the results of well controlled prospective clinical trials.

Topics: Brachytherapy; Female; Gold Radioisotopes; Humans; Ovarian Neoplasms; Phosphorus Radioisotopes; Radioisotopes

Topics: Adult; Breast Feeding; Chromium; Chromium Compounds; Cystadenocarcinoma; Female; Humans; Infant, Newborn; Injections, Intraperitoneal; Milk, Human; Ovarian Neoplasms; Phosphates; Phosphorus Radioisotopes; Pregnancy; Pregnancy Complications, Neoplastic

Topics: Brachytherapy; Colloids; Contrast Media; Female; Humans; Ovarian Neoplasms; Peritoneal Cavity; Phosphorus Radioisotopes; Radiography; Radionuclide Imaging; Sulfur; Technetium; Technetium Tc 99m Sulfur Colloid

Topics: Antineoplastic Agents; Castration; Drug Therapy, Combination; Female; Humans; Hysterectomy; Ovarian Neoplasms; Phosphorus Radioisotopes

New biologic information has led to a therapeutic program in Stage III ovarian cancer that considers the whole peritoneal cavity the tumor-bearing region and that uses intraperitoneal administration of ovarian cancer antiserum, intraperitoneal P-32, delayed split abdominal irradiation, and chemotherapy. The survival for those patients completing irradiation was 85%. Forty-nine patients with advanced (Stage III, IV, or recurrent) ovarian cancer have been treated with combinations of the present agents. Twenty-two patients have received intraperitoneal ovarian cancer antiserum without significant toxicity. Extensive staging has been a requirement for initial evaluation and includes maximal surgical resection, omentectomy, TAH and BSO, nodal biopsies, and peritoneal cytology. Nineteen patients had 5-mm nodules or less residual disease and were treated with colloidal P-32, abdominal irradiation, and chemotherapy; five of these patients received intraperitoneal antiserum before cytotoxic therapy. The four-year cumulative survival is 84%, and the disease-free survival 43%. A randomized prospective study is now examining the value of antiserum therapy. New experimental data from our laboratory indicate 1) the value of 2/3 biomarkers (alpha globulin and free secretory protein) in following patients for remission of disease and 2) the probability of the development of more effective antiserum with high specific titer. Studies of the radiosensitivity of ovarian cancer indicate the tumor was not different from other solid tumors. Our studies indicate the role of radiation therapy as a cytoreductive agent should be integrated in multimodality therapy and that the immune system offers new possibilities in amplifying therapeutic results.

Topics: Alpha-Globulins; Antigens, Neoplasm; Antineoplastic Agents; Biopsy; Brachytherapy; Carcinoembryonic Antigen; Cystadenocarcinoma; Female; Humans; Hysterectomy; Immunization, Passive; Neoplasm Staging; Omentum; Ovarian Neoplasms; Phosphorus Radioisotopes; Radioisotope Teletherapy

Topics: Female; Humans; Intraoperative Care; Ovarian Cysts; Ovarian Neoplasms; Phosphorus Radioisotopes; Radioisotope Dilution Technique; Uterine Neoplasms

An investigation of the efficacy of astatine-211--tellurium colloid for the treatment of experimental malignant ascites in mice reveals that this alpha-emitting radiocolloid can be curative without causing undue toxicity to normal tissue. By comparison, negatron-emitting phosphorus-32 as colloidal chromic phosphate had no antineoplastic activity. The most compelling explanation for this striking difference is the dense ionization and short range of action associated with alpha-emission. These results have important implications for the development and use of alpha-emitters as radiocolloid therapy for the treatment of human tumors.

Topics: Alpha Particles; Animals; Ascites; Astatine; Cell Survival; Chromium; Chromium Compounds; Colloids; Female; Mice; Neoplasm Transplantation; Neoplasms, Experimental; Ovarian Neoplasms; Phosphates; Phosphorus Radioisotopes; Radioisotopes; Tellurium; Transplantation, Homologous

Increasing the injection volume had no significant long-term effect on the distribution or tissue dose of intraperitoneal 32P in New Zealand white rabbits. Further, the range of doses and dose rates observed in the rabbit had little effect in vitro against either a human ovarian cancer line or an established Chinese hamster cell line. Demonstrable kill of human ovarian cancer cells was achieved, however, for initial 32P dose rates of 11 and 22 rad/h (0.11 and 0.22 Gy/h). From these results, it is estimated that administered 32P activities ranging from about 75-150 mCi (2.8-5.6 GBq) would be required for significant tumoricidal effects in ovarian cancer patients.

Topics: Animals; Autoradiography; Carcinoma; Cell Line; Chromium; Chromium Compounds; Cricetinae; Diaphragm; Dose-Response Relationship, Radiation; Female; Injections, Intraperitoneal; Ovarian Neoplasms; Phosphates; Phosphorus Radioisotopes; Radiotherapy Dosage; Rats

One hundred sixty-seven patients with clinical State I carcinoma of the endometrium were treated primarily by operation consisting of total abdominal hysterectomy, bilateral salpingo-oophorectomy, selective pelvic and para-aortic lymphadenectomy, and cytologic testing of peritoneal washings. Twenty-six (15.5%) of the 167 patients had malignant cells identified on cytologic examinations of peritoneal washings. Recurrence developed in 10 of these 26 (34.0%) compared to 14/141 (9.9%) patients with negative cytologic testing. Of the 26 patients, 13 (50%) had disease outside of the uterus at operation and seven have died of disease (54%). Thirteen patients had malignant cells in the peritoneal washings but no disease outside of the uterus and six (46%) of these have died of disseminated intra-abdominal carcinomatosis. On the basis of the poor outcome of those patients who had malignant cells in the peritoneal washings in the 167 patients studied, a plan of treating such patients with intraperitoneal radioactive chromic phosphate suspension (P-32) was instituted. Twenty-three subsequent patients with clinical Stage I carcinoma of the endometrium were found to have malignant cells in the peritoneal fluid. All 23 received intra-abdominal P-32 suspension instillation after operation. There have been three recurrences with two patients dying of disease. All of the three recurrences appeared at sites distant from the abdominal cavity. Peritoneal cytologic examination appears to be an important factor in the prognosis of endometrial cancer and, when the washings are positive for malignant cells, intraperitoneal chronic phosphate therapy appears to be efficacious.

Topics: Adenocarcinoma; Ascitic Fluid; Chromium; Chromium Compounds; Female; Humans; Lymphatic Metastasis; Neoplasm Metastasis; Ovarian Neoplasms; Phosphates; Phosphorus Radioisotopes; Prognosis; Uterine Cervical Neoplasms; Uterine Neoplasms

With an Anger camera for scintigraphic recording of bremsstrahlung radiation from phosphorus-32, the distribution of intraperitoneal colloidal chromic phosphate was followed in patients with gynecologic tumors. Sequential pelvic, abdominal, and thoracic scintiphotos over a three-week period revealed rapid and persistent focal aggregation of the radiocolloid with no change in pelvic or peritoneal radionuclide distribution patterns. Visualization of intrathoracic lymph node uptake did not correlate with the presence of diaphragmatic tumor. This study demonstrates the utility of scintigraphy for monitoring the distribution of intraperitoneal beta emitters and the need for developing alternative methods of administering these therapeutic agents to achieve more uniform patterns of distribution.

Topics: Brachytherapy; Female; Humans; Ovarian Neoplasms; Peritoneal Cavity; Phosphorus Radioisotopes; Radionuclide Imaging; Tissue Distribution; Uterine Neoplasms

Radiophosphorus (32P) has become the preferred radioisotope for intraperitoneal radiotherapy in the adjuvant treatment of ovarian cancer. In a study of the distribution and tissue dose of intraperitoneally administered 32P in rabbits, effective half-lives of 32P and the radiation dose absorbed by intra-abdominal tissues were determined. Results show that 32P is not uniformly distributed over the peritoneal surfaces and that many areas are minimally irradiated. It is concluded that a significant fraction of the 32P distribution is systemic and that the beta-ray dose for intra-abdominal tissues is much lower than suggested by theoretical models.

Topics: Animals; Autoradiography; Chromium; Female; Injections, Intraperitoneal; Models, Biological; Ovarian Neoplasms; Peritoneum; Phosphates; Phosphorus Radioisotopes; Rabbits; Radiotherapy Dosage; Time Factors; Tissue Distribution

Topics: Animals; Chromium; Dogs; Female; Lymphatic Metastasis; Neoplasm Metastasis; Ovarian Neoplasms; Peritoneal Neoplasms; Phosphates; Phosphorus Radioisotopes; Radiography; Tissue Distribution

Between January 1960 and September 1972, 104 patients with limited epithelial carcinoma of the ovary received intraperitoneal radiocolloid. Fifty-six of these patients also received external beam radiation therapy to the pelvis (pelvic RT). Five-year actuarial no-evidence-of-disease survival rates were 95% for stage Iai, 82% for Iaii, 73% for Ib, 67% for Ic, 67% for IIa, 67% for IIb without gross residual tumor (GRT), 25% for IIb with GRT, and 50% for III with minimal or no GRT. The addition of pelvic RT following radiocolloid could not be shown to affect survival of patients with Stage I and IIa tumors. Small bowel complications were related to the use of pelvic RT, however, occurring in 2.2% of patients treated with radiocolloid alone and 24% of patients treated with colloid and pelvic RT (p less than 0.005). In patients who underwent abdominal surgery following treatment of ovarian cancer, no excessive complication rate was observed. We conclude that for patients with stages Iaii through IIa, postoperative radiocolloid appears to provide the greatest chance of survival with the least chance of complication. For patients with Stage IIb and III lesions in whom there is minimal or no GRT, radiocolloid followed by pelvic RT produced survival rates comparable or superior to any other form of postoperative therapy.

Topics: Adult; Aged; Cystadenocarcinoma; Cystadenoma; Female; Gold Colloid, Radioactive; Humans; Intestine, Small; Middle Aged; Neoplasms, Multiple Primary; Ovarian Neoplasms; Peritoneal Cavity; Phosphorus Radioisotopes; Radiation Injuries; Radiotherapy, High-Energy

Topics: Antineoplastic Agents; Female; Humans; Middle Aged; Neoplasm Staging; Ovarian Neoplasms; Phosphorus Radioisotopes

At the Johns Hopkins Hospital between the years 1967 and 1973, 40 patients with primary ovarian carcinoma were treated with radioactive phosphorus. Of these, 19 were treated with external radiation in addition. The morbidity from the radioactive phosphorus alone was negligible. Dosages of less than 5000 rads to the pelvis were usually well tolerated even when given in combination with the isotope. Pathologic changes in the bowel are discussed.

Topics: Carcinoma, Papillary; Cobalt Radioisotopes; Epithelium; Female; Humans; Ovarian Neoplasms; Phosphorus Radioisotopes; Radioisotope Teletherapy; Radiotherapy Dosage; Retrospective Studies; Tennessee

Topics: Animals; Cobalt Radioisotopes; Disease Models, Animal; Female; Injections, Intraperitoneal; Mammary Neoplasms, Experimental; Mice; Mice, Inbred C3H; Neoplasm Metastasis; Neoplasm Transplantation; Osteosarcoma; Ovarian Neoplasms; Peritoneal Neoplasms; Phosphorus Radioisotopes; Radioisotope Teletherapy; Sarcoma, Experimental

The addition of intraperitoneal colloidal radioactive chromic phosphorus following total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy in women with Stage I ovarian cancer does not cause significant morbidity. Moreover, our preliminary results suggest that this regimen appears to increase the rate of local control of disease. In 21 unselected patients, there was 1 incident of small bowel obstruction. Fourteen of these patients have been followed for at least 1 1/2 years; all are alive without evidence of disease. These facts suggest that a national prospective study to investigate the efficacy of this treatment for Stage I ovarian cancer is warranted.

Topics: Adult; Aged; Castration; Colloids; Fallopian Tubes; Female; Humans; Hysterectomy; Middle Aged; Omentum; Ovarian Neoplasms; Phosphorus Radioisotopes; Postoperative Complications; Prospective Studies; Radiotherapy Dosage; Time Factors

Topics: Abdomen; Female; Humans; Injections, Intraperitoneal; Neoplasm Seeding; Ovarian Neoplasms; Pancreatic Neoplasms; Peritoneal Cavity; Phosphorus Radioisotopes; Radionuclide Imaging

Cancer of the ovary is the leading cause of death from gynecologic cancer. The constant challenge presented by ovarian cancer is that about 11,000 women die from ovarian cancer each year and the results in 1974 are no better than have been achieved in the previous two decades. Standard practice of treatment for truly invasive common epithelial ovarian cancer includes total hysterectomy, bilateral salpingo-oophorectomy, appendectomy, omentectomy, and post-surgical insertion of tubes and administration of P32 (if the disease is of limited extent). Although it is occasionally necessary to resect isolated segments of bowel, exenterative or ultraradical surgery in the management of ovarian cancer is not usually chosen because of the natural history of the disease. However, aggressive surgery is indicated not so much because it is curative, but because it potentiates other forms of treatment. All stages I through IV are treated surgically, to remove as much tumor as possible without running a risk of a gastrointestinal or genitourinary fistula. Radiation therapy has been utilized in addition to the surgical therapy in stage IV to control supraclavicular and/or inguinal node involvement. Single agent alkylating chemotherapy is chosen for the treatment of common epithelial ovarian cancers. Combination chemotherapy does not produce better results at this time, except in the treatment of embryonal tumors. The treatment of the common epithelial tumors by stage is outlined. The treatment of germ cell tumors, gonadal stromal tumors, ovarian tumors in childhood, ovarian tumors in pregnancy, as well as tumors not specific for the ovary, will also be discussed.

Topics: Adolescent; Adult; Alkylating Agents; Appendectomy; Castration; Child; Dysgerminoma; Female; Granulosa Cell Tumor; Humans; Hysterectomy; Lymphatic Metastasis; Neoplasm Metastasis; Neoplasms, Gonadal Tissue; Omentum; Ovarian Neoplasms; Pelvic Exenteration; Phosphorus Radioisotopes; Pregnancy; Pregnancy Complications; Radiotherapy; Sarcoma; Sertoli Cell Tumor; Teratoma

Topics: Adnexa Uteri; Bibliography, National; Blood Cells; Bone Marrow Cells; Chemotherapy, Cancer, Regional Perfusion; Endocrine System Diseases; Estrogens; Female; Follow-Up Studies; Humans; Hysterectomy; Kidney; Lymphography; Ovarian Neoplasms; Phosphorus Radioisotopes; Radiotherapy Dosage; Rural Population; Sex Chromatin; Thiotepa; Urban Population; USSR

Topics: Animals; Carcinoma; Carcinoma 256, Walker; Cells, Cultured; Chromatography, Thin Layer; Cyclophosphamide; Female; Humans; Mass Spectrometry; Nitrogen Mustard Compounds; Ovarian Neoplasms; Oxazoles; Phosphorus Radioisotopes; Piperazines

Topics: Alkylating Agents; Ascites; Chlorambucil; Dactinomycin; Drug Therapy, Combination; Female; Fluorouracil; Humans; Intestinal Fistula; Intestinal Obstruction; Medroxyprogesterone; Methotrexate; Ovarian Neoplasms; Patient Care Team; Phosphorus Radioisotopes; Progesterone; Radiotherapy Dosage; Thiotepa; Triaziquone; Vinblastine

Topics: Adult; Aged; Ascites; Computers; Evaluation Studies as Topic; Female; Gold Isotopes; Humans; Middle Aged; Ovarian Neoplasms; Phosphorus Radioisotopes; Portugal; Retrospective Studies

DNA was extracted from [(3)H]thymidine-labeled Marek's disease virus (MDV) and purified by two cycles of CsCl gradient centrifugation in a fixed-angle rotor. The DNA was transcribed in vitro into (32)P-labeled complementary RNA (cRNA). MDV cRNA did not hybridize with DNA from chicken embryo fibroblast cultures or from chicken spleen, but hybridized efficiently with DNA from MDV particles or MDV-infected cell cultures. Five Marek's disease tumors from different chickens and different organs (ovary, liver, testis) were all found to contain MDV DNA sequences. The relative amount of MDV DNA varied from tumor to tumor and was between 3 and 15 virus genome equivalents per cell. The content of virus DNA per cell in spleens from tumor-bearing chickens was much lower than in tumors from the same animals. MDV-infected cell cultures contained a large proportion (28-59%) of virus antigen-positive cells, as measured by immunofluorescence, but tumor cells were negative in this respect (<0.02% positive cells). These data indicate that MDV is present in a provirus form in tumor cells.

Topics: Animals; Base Sequence; Centrifugation, Density Gradient; Chick Embryo; DNA, Viral; Ducks; Embryo, Nonmammalian; Female; Fibroblasts; Fluorescent Antibody Technique; Herpesviridae; Liver Neoplasms; Male; Marek Disease; Microscopy, Electron; Neoplasms, Experimental; Nucleic Acid Hybridization; Ovarian Neoplasms; Phosphorus Radioisotopes; RNA, Viral; Testicular Neoplasms; Tritium; Virus Cultivation