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J Fanning

Publications and source records attributed to J Fanning.

At least 55 records · Page 3Linked to original sources

High-dose-rate brachytherapy in primary stage I and II vaginal cancer.

Thirteen patients with primary vaginal cancer were treated with external beam irradiation and high-dose-rate brachytherapy. Median age was 65 years old. Five tumors were stage I, 4 stage IIA, and 4 stage IIB. Twelve tumors were squamous and 11 were moderately or poorly differentiated. Median tumor diameter was 4 cm. Patients were treated with external beam irradiation (4500 cGy) and high-dose-rate brachytherapy (2000-2800 cGy in three to four fractions). All 13 patients had a complete response. Local control was achieved in 12 patients (92%) at a median follow-up of 2.6 years. No acute or chronic intestinal or bladder grade 3 or 4 toxicity was observed. Moderate to severe vaginal stenosis occurred in 6 patients (46%). Treatment of stage I and II primary vaginal cancer with external beam irradiation and high-dose-rate brachytherapy appears to produce a high response rate, local control, and survival with minimal complications.

Adult↗

High-dose cisplatin carboplatin chemotherapy in primary advanced epithelial ovarian cancer.

The purpose of the study was to maximize platinum dose intensity in women with ovarian cancer by combining cisplatin and carboplatin and using Day 1 and 8 scheduling. Thirty-two consecutive patients with primary stage 3 or 4 epithelial ovarian cancer underwent radical cytoreductive surgery followed by high-dose cisplatin carboplatin chemotherapy. Twenty-eight tumors (88%) were stage 3C or 4 and 20 (62%) were grade 3. Following radical cytoreductive surgery, 21 patients (66%) had less than 5 mm of residual disease. The first 2 patients treated with 75 mg/m2 cisplatin and 150 mg/m2 carboplatin on Days 1 and 8 every 28 days for 5 cycles developed severe and prolonged thrombocytopenia. As a result, the dose was reduced to 70 mg/m2 cisplatin and 100 mg/m2 carboplatin for the remaining 30 patients, representing a monthly platinum dose of 207 mg/m2. Projected platinum dose intensity was 700 mg/m2 cisplatin and 1000 mg/m2 carboplatin delivered over 16 weeks. Eleven patients (44%) received 100% and 27 patients (84%) received > 90% projected platinum dose intensity. Median projected platinum dose intensity received was 97%. Grade 4 thrombocytopenia occurred in 43 cycles (28%) and grade 3 peripheral neuropathy occurred in 15 patients (47%). Central nervous system toxicity occurred frequently: ototoxicity, 66%; decreased taste, 50%; optic toxicity, 41%; memory loss, 34%. Twenty-seven patients (84%) had a clinical complete response and 7 patients (44%) undergoing second-look laparotomy had a pathologic complete response. The majority of clinical responses were based on CA-125. Median survival has not been reached at 2.1 years. Median progression-free survival is 1.4 years. Combining cisplatin and carboplatin using Day 1 and 8 scheduling allows maximum hematologic platinum dose intensity; however, peripheral neuropathy is prohibitive. Day 1 and 8 scheduling does not appear to prevent peripheral neuropathy when delivering dose-intense platinum chemotherapy. Central nervous system toxicity of high-dose platinum is more common than previously reported.

Aged↗

Meta-analysis.

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Female↗

Monoclonal antibodies in ovarian and prostate cancer.

Radioimmunoscintigraphy (RIS)--using radiolabeled monoclonal antibodies (MoAbs) to image disease--is a growing subspecialty of nuclear medicine. RIS of the reproductive tracts of men and women has shown encouraging results in imaging both primary lesions and metastases of these cancers. Ovarian cancer is the most fatal gynecologic cancer in the United States, and prostate cancer is the most prevalent form of cancer in men. Several MoAbs against reproductive tumor antigens were used with limited success in clinical trials before 1989. Most recently, MoAbs CYT-103 (satumomab pendetide) and OV-TL 3 have shown promise as safe, sensitive imaging tools for ovarian cancer. Although to date more agents have been used to image ovarian carcinoma than prostate cancer, research has been restimulated in prostate carcinoma imaging because of development of a promising MoAb conjugate, CYT-356. Radionuclide indium-111 appears to be the most promising radiolabeled to date for ovarian and prostate carcinoma RIS performed in the United States. In future clinical trials, consideration of safety issues and a standardization of methods among institutions using RIS are needed before the use of MoAb technology in cancer imaging will become routine. Comparative studies with more traditional methods like computed tomography are needed, as well as more trials comparing radioimmunoscintigraphic findings with pathological evidence.

Female↗

In-111 CYT-103 immunoscintigraphy in the imaging of ovarian carcinoma.

Fifteen presurgical patients with a history of ovarian carcinoma were evaluated with immunoscintigraphy using the In-111-labeled monoclonal antibody conjugate CYT-103. Twelve of these patients had residual neoplasia at time of laparotomy. A single intravenous dose of the radiolabeled monoclonal antibody was given to these patients before restaging laparotomy. All patients also underwent CT scanning of the abdomen and pelvis before laparotomy. Immunoscintigraphy detected the presence of disease in 10 of 12 patients before surgery, whereas CT scanning detected disease in only 6 of these 12 women. The results of this study indicate that immunoscintigraphy using In-111 CYT-103 is more sensitive than CT and may add useful information to the preoperative evaluation of women with ovarian carcinoma.

Antibodies, Monoclonal↗

Meta-analysis of cisplatin, doxorubicin, and cyclophosphamide versus cisplatin and cyclophosphamide chemotherapy of ovarian carcinoma.

OBJECTIVE: To compare the survival with cisplatin, doxorubicin (Adriamycin), and cyclophosphamide versus that of cisplatin and cyclophosphamide in women with advanced epithelial ovarian cancer, to evaluate the effect of dose intensity, and to evaluate meta-analysis methodology. METHODS: Meta-analysis was done on 30 studies of 2060 women with stages III and IV epithelial ovarian cancer. All had 3-year survival data, adequate follow-up, no other chemotherapy, no radiation therapy, and had information for various prognostic variables (age, stage, grade, and residual disease). We used four different methods of meta-analysis: pooled published data and modified effect-size analyses of the entire group (30 studies), and pooled published data and effect-size analyses of the subset of five prospective randomized studies. RESULTS: Three-year survival for the entire group was 43% for cisplatin, doxorubicin, and cyclophosphamide versus 36% for cisplatin and cyclophosphamide; for the five prospective randomized studies, the rates were 46 and 35%, respectively. The survival advantage of cisplatin, doxorubicin, and cyclophosphamide was statistically significant when analyzed by the pooled published data and modified effect-size meta-analysis of the entire group and the pooled published data meta-analysis of the five prospective randomized studies. The effect-size meta-analysis of the five prospective studies did not reach statistical significance. Total dose intensity and doxorubicin dose intensity were not significantly associated with survival advantage in cisplatin, doxorubicin, and cyclophosphamide use. CONCLUSIONS: There seems to be a survival advantage to treatment with cisplatin, doxorubicin, and cyclophosphamide versus treatment with cisplatin and cyclophosphamide. We believe this to be due to the properties of multiagent chemotherapy (the addition of doxorubicin) rather than to increased dose intensity. In addition, we believe that physicians need to familiarize themselves with meta-analysis methodology.

Antineoplastic Combined Chemotherapy Protocols↗

Laser vaporization conization.

Laser vaporization conization is a modified technique for the diagnosis and treatment of cervical intraepithelial neoplasia. Two circles are marked on the cervix with the laser; the inner circle outlines the circumference of the conization specimen, while the outer one outlines an area 3 mm peripheral to all colposcopically abnormal tissue. The area between the circles is vaporized to 7 mm. This initial vaporization allows easier manipulation of the conization specimen. Laser conization is then performed. This technique is significantly easier to perform than laser excisional conization or combination excisional-vaporization conization and thus is ideal for teaching residents laser conization. Besides ease of performance, laser vaporization conization retains the advantages of laser vaporization and provides a specimen for pathologic review. In this study the median laser time was 14 minutes. There was minimal operative hemorrhaging, and only one patient (2%) developed a secondary cervical hemorrhage. A significant laser artifact was present in one case (2%). One case of invasive squamous cell cancer was diagnosed.

Adult↗

Cervical implantation metastasis by endometrial adenocarcinoma.

A distinct type of cervical involvement by endometrial cancer is reported and termed cervical implantation metastasis. It is believed to result from implantation of endometrial cancer on the denuded endocervix after fractional dilatation and curettage (D & C). The histologic criteria for diagnosis are: (1) the cervical implantation metastasis must be imbedded in the endocervical epithelium or superficial stroma surrounded by an implantation site of inflammatory cells and granulation tissue (free-floating cancer cells above the cervical mucosa are not acceptable as implantation tissue), (2) the histologic findings of the cervical implantation metastasis must be similar to those of the endometrial adenocarcinoma in the uterine corpus, (3) the cervical implantation metastasis must be separate from the primary tumor with no evidence of direct extension, and (4) the cervical implantation metastasis should be surrounded by nonneoplastic endocervical glands with no transition between the two. Of the 176 patients who underwent fractional D & C before hysterectomy, nine (5%) were found to have cervical implantation metastasis. No patients had cervical implantation metastasis who did not undergo fractional D & C before hysterectomy. When stratified according to stage, grade, and myometrial invasion, there was no statistically significant difference in the recurrence rate between patients with or without cervical implantation metastasis. It appears that cervical implantation metastasis does not alter prognosis or require specific treatment.

Adenocarcinoma↗

Five-year survival for cisplatin-based chemotherapy versus single-agent melphalan in patients with advanced ovarian cancer and optimal debulking surgery.

The purpose of this study was to evaluate 5-year survival and 5-year progression-free survival in previously untreated patients with advanced ovarian cancer treated with single-agent melphalan in which very few patients underwent optimal debulking surgery (less than 2 cm residual) as compared with the patients treated with Cisplatin-based chemotherapy in which most patients underwent optimal debulking surgery. Significant increases in 5-year survival and 5-year progression-free survival were noted as we changed from the melphalan trial, in which only 14% underwent optimal debulking surgery, to PAC-H, in which 57% and the PAC trial in which 90%, respectively, underwent optimal debulking surgery. However, for those patients whose tumors were optimally debulked in the three trials, there were no statistically significant differences in median survival, median progression-free survival, 5-year survival, or 5-year progression-free survival in those patients treated with melphalan, PAC-H, or PAC. Without optimal debulking surgery, Cisplatin-based multiagent chemotherapy offered a small survival advantage. These results are similar to that reported by Gruppo Interregionale Cooperativo Oncologico Ginecologia, in which survival curves were identical for all the subgroups of chemotherapy regimens for those patients with residual disease less than 2 cm at the onset of chemotherapy whether they received (1) cyclophosphamide; (2) cyclophosphamide and Adriamycin; (3) cyclophosphamide, Adriamycin, and Cisplatin; (4) cyclophosphamide, Adriamycin, and hexamethylmelamine; (5) Cisplatin and cyclophosphamide; (6) low-dose Cisplatin; (7) high-dose Cisplatin; or (8) carboplatin.

Antineoplastic Combined Chemotherapy Protocols↗

Development of lung metastases after curative intraperitoneal chemotherapy in a rat colon cancer model.

A model of colon peritoneal carcinomatosis was developed by injecting 5 x 10(7) viable tumor cells intraperitoneally into Fisher 344 rats. All 40 control rats developed bulky abdominal tumor with ascites and died of peritoneal carcinomatosis and bowel obstruction (median survival 5 weeks). One day after tumor implantation, treatment group rats received a single intraperitoneal injection of single agent or combination chemotherapy. The most active intraperitoneal single agents were 5-fluorouracil, cisplatin, and etoposide. The most active combination was 5-fluorouracil and cisplatin. Combination chemotherapy produced a significant increase in median, 10-week, and 20-week survival (vs control and single agent). Six of 11 (55%) rats treated with intraperitoneal combination chemotherapy dying between 10-20 weeks died of lung metastasis with cure of intraperitoneal tumor. The increased ability of intraperitoneal combination chemotherapy to cure intraperitoneal disease was offset by the development of lung metastasis.

Adenocarcinoma↗

Prognostic significance of the extent of cervical involvement by endometrial cancer.

The prognostic significance of the extent of cervical involvement by endometrial cancer is impossible to determine from the literature because previous reports have included fractional dilatation and curettage for staging, preoperative radiotherapy, and surgical stage III and IV disease. Therefore, we reviewed and restaged according to the new FIGO system all patients with endometrial cancer from January 1981 to December 1989. Of 180 patients undergoing hysterectomy for endometrial cancer, 20 had surgical stage II disease. No patient received preoperative radiotherapy. None of 12 patients (0%) with stage IIA disease developed recurrence, while 5 of 8 (63%) with stage IIB disease recurred (P less than 0.01). All 5 recurrences were in extrapelvic sites. Endocervical stroma invasion appears to import a statistically significant worse prognosis than endometrial glandular involvement.

Adenocarcinoma↗

Phase II trial of cisplatin, adriamycin, and etoposide for metastatic endometrial adenocarcinoma.

Twenty patients with metastatic or recurrent endometrial adenocarcinoma not amenable to surgery or radiation were treated with monthly cisplatin (20 mg/m2 x 3), etoposide (75 mg/m2 x 3), Adriamycin (40 mg/m2) (PAV) and Megace. Patient characteristics were as follows: grade 3 differentiation, 55%; papillary subtype, 15%; prior radiotherapy, 70%; prior chemotherapy, 10%; and prior hormonal therapy, 20%. Hematologic toxicity was significant but acceptable: WBC nadirs, 50%; platelet nadirs, 40%. There was no hematologic mortality. There was a 75% objective response rate and a 55% complete response rate with PAV. The median survival was 15+ months, the 2-year survival was 42%, and the 2-year progression-free survival was 20%. PAV appears to be an active combination with acceptable toxicity in the treatment of metastatic or recurrent endometrial cancer, and we believe that phase III evaluation is indicated.

Adenocarcinoma↗

Serial CA 125 levels during chemotherapy for metastatic or recurrent endometrial cancer.

The purpose of this study was to evaluate the role of serial CA 125 in monitoring disease status during chemotherapy in women with metastatic or recurrent endometrial cancer. CA 125 was measured in 21 women receiving cisplatin, etoposide, and Adriamycin for a total of 275 courses of chemotherapy (median eight). Eight of ten patients had elevated pre-therapy CA 125 levels (median 233 U/mL). CA 125 became and/or remained negative in all 20 women with responding or stable disease and was elevated in all nine patients who relapsed. The median level at the time of relapse was 56 U/mL. Levels were elevated before clinical relapse in five of nine patients (56%). Serial CA 125 may aid in the management of women receiving chemotherapy for advanced or recurrent endometrial cancer.

Aged↗

Immunotherapy of gynecologic malignancies.

Systemic Corynebacterium parvum and BCG have limited activity in gynecologic malignancies. Although intraperitoneal C. parvum is active, its toxicity is prohibitive. Intraperitoneal alpha-interferon is an active second line agent for minimal residual disease following combination chemotherapy. Intraperitoneal interferon trials are ongoing. Alpha-interferon is also active against lower genital tract condyloma acuminata. Sufficient numbers of patients have not been evaluated to determine the activity of interleukin-2(IL-2) in gynecologic malignancies. Radioisotope labeled monoclonal antibodies can image gynecologic malignancies and may have a future therapeutic role. The last decade has witnessed a substantial growth in immunotherapy and has demonstrated a role for biologic agents in cancer therapy. Continued improvement in biologic therapies should lead to major advances in gynecologic cancer diagnosis and therapy.

Female↗

Influence of grade, histologic subtype, and timing of radiotherapy on outcome among patients with stage II carcinoma of the endometrium.

In 1988, the Federation of International Gynecologic Oncologists (FIGO) adopted a new staging system mandating preradiotherapy surgical staging in endometrial cancer. To evaluate the potential impact of this recommendation on patients with cervical involvement (stage II), an analysis of 184 consecutive patients with clinical or pathologic stage II carcinoma of the endometrium treated with definitive intent at three institutions was performed. Median follow-up time was 5.7 years. Treatment consisted of total abdominal hysterectomy and bilateral salpingo-oophorectomy with preoperative radiation therapy (RT) (54%), postoperative RT (37%), or both (1%); definitive RT (7%); or radical hysterectomy (1%). The median total RT dose for combined intracavitary and external beam or either alone was 70.6 Gy with a range of 32.4-105.0 Gy. The overall 5-year survival rate and disease-free survival (DFS) rate at 5 years were 70 and 79%, respectively. Of patients treated with surgery and adjuvant radiation, 13% (22/168) had infield pelvic failure (PF) and 18% (31/168) had distant metastases (DM). Patterns of failure in patients receiving preoperative and postoperative radiotherapy are presented. Univariate analysis of pretreatment and treatment factors, including histology, grade, clinical stage, extent of cervical involvement, and timing of adjuvant radiation, revealed histology and grade to be significant predictors of DFS, PF, and DM. Clinical stage was a significant predictor of DFS only in univariate analysis. Multivariate analysis found only histology (P less than 0.001) and grade (P = 0.002) to be predictors of DFS. From this review, we conclude that histology and grade are independent predictors of DFS, and more aggressive treatment should be directed at patients with stage II endometrial cancer found to have high grade adenocarcinoma or papillary serous/clear cell histologic variants. The timing of radiotherapy was not an independent predictor of outcome; therefore, preradiotherapy surgical staging should not impact on DFS and should provide surgicopathologic information to tailor treatment and predict prognosis. The FIGO clinical staging system used in this analysis was not an independent predictor of outcome, and future multivariate analyses will be necessary to test the predictive value on outcome of the new 1988 FIGO surgical staging.

Female↗

Intraoperative frozen section diagnosis of depth of myometrial invasion in endometrial adenocarcinoma.

From January 1981 to December 1988, a prospective trial was conducted on 216 consecutive patients undergoing hysterectomy for FIGO stage I endometrial adenocarcinoma to determine the accuracy of intraoperative frozen section (IFS) diagnosis of depth of myometrial invasion. IFS and D&C diagnoses were compared to the permanent section diagnosis to determine their accuracy. Patients with an IFS or D&C diagnosis of grade 3 carcinoma, deep myometrial invasion, cervical invasion, or adnexal involvement were considered high risk for paraaortic nodal metastasis, and paraaortic lymphadenectomy was performed. IFS correctly diagnosed the depth of myometrial invasion in 194 of 204 cases (95%). The sensitivity of IFS diagnosis of deep invasion was 87%, the specificity was 99%, the positive predictive value was 98%, and the negative predictive value was 94%. Grade, subtype, cervical invasion, and adnexal involvement were also accurately diagnosed. Based on IFS and D&C diagnosis, paraaortic lymphadenectomy was performed in 32% of patients, while 68% were considered low risk and were spared paraaortic lymphadenectomy. Eight patients (5%) were incorrectly diagnosed as low risk and did not have paraaortic lymphadenectomy performed. Sixty-five of seventy-three (90%) patients considered high risk on permanent section had paraaortic lymphadenectomies performed on the basis of IFS and D&C diagnosis. Inaccurate IFS diagnosis of depth of myometrial invasion can occur when tumor involves the uterine isthmus or cornua and when tumor invades areas of adenomyosis.

Adenocarcinoma↗

Comparison of cisplatin and carboplatin cytotoxicity in human ovarian cancer cell lines using the MTT assay.

In this study, we compared the cytotoxicity of cisplatin and carboplatin against a panel of human ovarian cancer cell lines using the MTT assay, a rapid colorimetric test that can be used to evaluate the number of residual viable tumor cells following chemotherapy. The established human ovarian cancer cell line OVCAR-3 and the recently isolated and characterized A721, A90, A286, A1, and A121A cell lines were evaluated for chemosensitivity. Each cell line was treated separately with cisplatin and carboplatin at concentrations ranging from 500 to 0.16 micrograms/ml. Various chemotherapeutic exposure periods (1, 4, 24, and 48 hr) were tested to determine maximal efficacy. All cell lines were more susceptible to cisplatin than carboplatin at all drug concentrations and all exposure periods tested (P = 0.005). The overall median 50% inhibitory concentration (ID50) for cisplatin was 107 micrograms/ml compared with 490 micrograms/ml for carboplatin P = 0.005). For both cisplatin and carboplatin a 24-hr exposure was significantly more cytotoxic than a 1-hr exposure (P = 0.003 and P = 0.006, respectively). These in vitro results suggest that cisplatin is significantly more cytotoxic than carboplatin against human ovarian cancer cell lines and that cisplatin should not be replaced by carboplatin in the treatment of advanced epithelial ovarian cancer until randomized trials using maximum dosing of the cisplatin-containing regimen are performed.

Adult↗