Standard therapies for prostate cancer including radiation, prostatectomy, and hormone ablation have significant toxicities and recurrence risk. HSV-tk gene therapy may be effective in combination with radiation therapy due to complementary mechanisms and distinct toxicity profiles. Mouse prostate tumors transplanted subcutaneously were treated by either gene therapy involving intratumoral injection of AdV-tk followed by systemic ganciclovir or local radiation therapy or the combination of gene and radiation therapy. Both single-therapy modalities showed a 38% decrease in tumor growth compared to controls. The combined treatment resulted in a decrease of 61%. In addition the combined-therapy group had a mean survival of 22 days versus 16.6 days for single therapy and 13.8 days for nontreated controls. To analyze systemic anti-tumor activity, lung metastases were generated by tail vein injection of RM-1 prostate cancer cells on the same day that they were injected subcutaneously. The primary tumors were treated as before with AdV-tk followed by ganciclovir, radiation, or the combination. The number of lung nodules was reduced by 37% following treatment with AdV-tk, whereas radiotherapy alone had no effect on metastatic growth. The combination led to an additional 50% reduction in lung colonization. Primary tumors that received the combination therapy had a marked increase in CD4 T cell infiltrate. This is the first report showing a dramatic systemic effect following the local combination treatment of radiation and AdV-tk. A clinical study using this strategy has been initiated and patient accrual is ongoing.

The American Association of Physicists in Medicine Task Group 43 reports, AAPM TG-43 and its update TG-43U1, provide an analytical model and a dosimetry protocol for brachytherapy dose calculations, as well as documentation and results for some sealed sources. The radionuclide 198Au (T(1/2)=2.70 days, Egamma=412 keV) has been used in the form of seeds for brachytherapy treatments including brain, eye, and prostate tumors. However, TG-43 reports have no data for 198Au seeds, and none have previously been obtained. For that reason, and because of the conversion of most treatment planning systems to TG-43 based methods, both Monte Carlo calculations (MCNP 4C2) and thermoluminescent dosimeters (TLDs) are used in this work to determine these data. The geometric variation in dose is measured using an array of TLDs in a solid water phantom, and the seed activity is determined using a high purity germanium detector (HPGe) and a well ionization chamber. The results for air kerma strength, Sk, per unit apparent activity, are 2.063 (MCNP) and 2.089 (measured) U mCi(-1), values close to those published in 1991 in the AAPM Task Group 32 report. The dose rate constant, lambda, is found equal to 1.115 (MCNP) and 1.095 (measured) cGy h(-1) U(-1). The radial dose function, g(r), anisotropy function, F(r, theta), and anisotropy factor, phi(an)(r), are also given.

Advances in imaging technology and implant technique have led to the resurgent interest and practice of brachytherapy for the treatment of prostate cancer. Brachytherapy is a form of radiation treatment in which radioactive sources are placed directly into the tumor; it offers the advantage of maximizing the radiation dose delivered to the tumor while sparing the adjacent normal tissue. Permanent implants have become an important component of radiation delivery. Interstitial gold radioisotope (Au‐198) implants for prostate cancer were introduced at Baylor College of Medicine in 1965. The rationale for using Au‐198, instead of the two most commonly used radioisotopes, Palladium‐103 (Pd‐103) and Iodine‐125 (I‐125), is discussed, and the Baylor implant technique is compared to that used in other centers. Retrospective review divides the patient population into pre‐ultrasound versus post‐ultrasound eras. Dosimetric calculation and disease control with the Au‐198 seed implant for prostatic cancer are reviewed for the two different eras; toxicity is evaluated in the post‐ultrasound era only. In the pre‐ultrasound era, 510 patients were treated with pelvic lymph node sampling and gold seed insertion of the prostate followed by external beam radiation. In the post‐ultrasound era, 54 patients were treated definitively with ultrasound‐guided transperineal Au‐198 implant followed by external beam irradiation. A small group of 30 patients in the post‐ultrasound era were evaluated for the efficacy of Au‐198 re‐implantation for locally recurrent disease. Semin. Surg. Oncol. 13:406‐418, 1997. © 1997 Wiley‐Liss, Inc.

From 1975 to 1987, 80 patients with bulky or barrel-shaped Stage IB cervical cancer were treated with preoperative irradiation and Cs-137 intracavitary implant therapy, before a planned extrafascial abdominal hysterectomy, using a consistent treatment policy. Of the hysterectomy specimens obtained, 37% were positive histologically at 89 +/- 2.3 days after the start of radiotherapy and at 4 to 6 weeks after the completion of radiation therapy. Sixty-three percent were negative after a total external and internal cervix irradiation dose of 9642 cGy at point T. The average point A dose contributed by intracavitary therapy was 2104 cGy. The survival rate at 5 years was 84%: At 10 years the survival rate was 78%. The failure pattern was analyzed for patients who had positive and negative specimens. The patients with positive specimens failed pelvically or pelvically and distantly. Patients with negative specimens failed in extrapelvic or distant metastatic sites. Preoperative radiotherapy led to excellent local and pelvic control of tumor, and the failures became predominantly distant metastases. The combined radiosurgical therapy was tolerated well and allowed surgical staging of disease. This permitted earlier and selective consideration of adjunctive therapy (i.e., paraaortic irradiation, chemotherapy, or chemoradiotherapy). The dose-response data give insight into the effects of photon radiotherapy on bulky or barrel Stage IB cervical cancers and correlate histologic status with failure pattern, outcome, and long-term survival.