Biomedical subjects
P DePriest
Publications and source records attributed to P DePriest.
A feasibility study of 252Cf neutron brachytherapy, cisplatin + 5-FU chemo-adjuvant and accelerated hyperfractionated radiotherapy for advanced cervical cancer.
PURPOSE: To evaluate the feasibility and toxicity of 252Cf neutron brachytherapy combined with hyperaccelerated chemoradiotherapy for Stage III and IV cervical cancers. METHODS AND MATERIALS: Eleven patients with advanced Stage IIIB-IVA cervical cancers were treated with 252Cf neutron brachytherapy in an up-front schedule followed by cisplatin (CDDP; 50 mg/m2) chemotherapy and hyperfractionated accelerated (1.2 Gy bid) radiotherapy given concurrently with intravenous infusion of 5-Fluorouracil (5-FU) (1000 mg/m2/day x 4 days) in weeks 1 and 4 with conventional radiation (weeks 2, 3, 5, and 6). Total dose at a paracervical point A isodose surface was 80-85 Gy-eq by external and intracavitary therapy and 60 Gy at the pelvic sidewalls. RESULTS: Patients tolerated the protocol well. There was 91% compliance with the chemotherapy and full compliance with the 252Cf brachytherapy and the external beam radiotherapy. There were no problems with acute chemo or radiation toxicity. One patient developed a rectovaginal fistula (Grade 3-4 RTOG criteria) but no other patients developed significant late cystitis, proctitis or enteritis. There was complete response (CR) observed in all cases. With mean follow-up to 26 months, local control has been achieved with 90% actuarial 3-year survival with no evidence of disease (NED). CONCLUSION: 252Cf neutrons can be combined with cisplatin and 5-FU infusion chemotherapy plus hyperaccelerated chemoradiotherapy without unusual side effects or toxicity and with a high local response and tumor control rate. Further study of 252Cf neutron-chemoradiotherapy for advanced and bulky cervical cancer are indicated. We found chemotherapy was more effective with the improved local tumor control.
Clinical evaluation of 252Cf neutron intracavitary therapy for primary endometrial adenocarcinoma.
BACKGROUND: A pilot feasibility study of the neutron-emitting radioisotope 252Cf was done on patients with uterine adenocarcinoma and medically inoperable disease or unfavorable G3 histologic findings. METHODS: 252Cf intracavitary therapy was combined with 40-45 Gy of fractionated whole-pelvis photon therapy. In select patients, hysterectomy was performed. RESULTS: Thirty-one patients with Stage I-III adenocarcinoma of the corpus uteri were treated with 252Cf neutron brachytherapy. The patients treated often were in poor general medical condition and had multiple chronic medical illnesses for which conventional radiation and surgery usually would not be recommended. 252Cf allowed short implant treatment time (hours), was usable in a small number of insertions (the average number of insertions was two), and was useful for treating large volume tumors. Stage and grade of the tumor were important determinants of patient survival. The 5-year actuarial survival was 83% for patients with Stage I disease but only 37% for those with Stage II disease (primarily adenosquamous cell carcinomas). The 5-year survival was 100% for patients with Grade 1 tumors, 88% for those with Grade 2 tumors, and 21% for those with Grade 3 tumors. CONCLUSION: 252Cf neutron brachytherapy was found to be an effective and well-tolerated therapy for endometrial carcinoma. The excellent therapeutic efficacy and good patient tolerance make it suitable for additional evaluation in future Phase II-III trials.
Schedule in Cf-252 neutron brachytherapy: complications after delayed implant therapy for cervical cancer in a phase II trial.
The objective of this study was to review severe complication frequency in a protocol study using a defined prescribed dose combined with fractionated whole pelvis radiotherapy to 40-45 Gy. The method used a dose of Cf neutrons to 35 Gy equivalents (relative biological effectiveness or RBE adjusted) to a total tumor dose of 80 Gy-eq in one to four implant sessions. Compliance was excellent, and most patients received two implants to 35 (0.4) (SE) Gy-eq in two sessions plus external radiation to a total point A or paracervical region dose of 80 (0.3) Gy-eqs. In patients who received delayed implants, the severe complication rate (pelvic necrosis, fistulas) was significantly greater (40% versus 3%). We postulate that neutron brachytherapy caused tumors to regress rapidly and completely, which allowed the neutron dose to adjacent radiosensitive organs (bladder, rectum, sigmoid colon, and bowel) to become excessive. The delayed Cf implant apparently contributed to the greater risk for normal tissue complications.
The growth response of BG-1 ovarian carcinoma cells to estradiol, 4OH-tamoxifen, and tamoxifen: evidence for intrinsic antiestrogen activation.
The influence of estrogen (E) and antiestrogen (AES) on the in vitro growth of BG-1 ovarian carcinoma cells, which express steroid receptors was examined (K. R. Geisinger, T. E. Kute, M. J. Pettenati, C. E. Welander, Y. Dennard, L. A. Collins, and M. E. Berens, Characterization of a human ovarian carcinoma cell line with estrogen and progesterone receptors, Cancer 63, 280-288, 1989). All determinations were simultaneously referenced under similar conditions to MCF-7 cells, a well-established cell line for modeling hormonal responses in breast cancer. In "complete" media containing fetal calf serum (FCS, 10%), MCF-7 cell numbers increased approximately 7 x in 7 days, remaining at this level Days 8-15. In contrast, BG-1 cells achieved similar numbers by Day 7, but showed apparent exponential growth over Days 8-15 to 15-20 x. Phenol red-free media containing 10% FCS (less than 20 pg estradiol (E2)/ml by RIA) was used to assess responses to E and AES. Growth of both MCF-7 and BG-1 cells slowed in E-free media. E2 (10 nM) stimulated the growth of both cell lines, yet was responsible for exponential increases during Days 8-15 only in BG-1 cell numbers (50-70 x). The metabolically active AES (4OH-tamoxifen, 50 nM) reduced E2-stimulated MCF-7 growth to 3-4 x, while tamoxifen (50 nM) had no effect. Rescue with 10 microM E2 fully overcame the AES inhibition of MCF-7 proliferation. In contrast, BG-1 cells experienced significant E2-stimulated growth reductions in the presence of either 4OH-tamoxifen or tamoxifen. E2 was observed to rescue BG-1 cells from both of these antagonists. We conclude that BG-1 ovarian carcinoma cells respond in vitro to E and AES. Moreover, by virtue of responses to tamoxifen, BG-1 cells may have an intrinsic capacity to hydroxylate tamoxifen to its active metabolite. This property of ovarian carcinoma cells might be worth exploiting in the design of more effective combination chemotherapy regimens.