Technical note: the calibration of 90Y-labeled SIR-Spheres using a nondestructive spectroscopic assay.

90Y-labeled SIR-Spheres are currently used to treat patients with hepatic metastases secondary to colorectal adenocarcinoma. In general, the prescribed activity is based on empirical data collected during clinical trials. The activity of the source vial is labeled by the manufacturer as 3.0 GBq +/- 10% and is not independently verified by the end user. This technical note shows that the results of a nondestructive spectroscopic assay of a SIR-Spheres sample was 26% higher than the activity stated by the manufacturer. This difference should not impact the current empirical prescription method but may be problematic for patient-specific dosimetry applications, such as image-based dosimetry.

Multi-species prostate implant treatment plans incorporating 192Ir and 125I using a Greedy Heuristic based 3D optimization algorithm.

The goals of interstitial implant brachytherapy include delivery of the target dose in a uniform manner while sparing sensitive structures, and minimizing the number of needles and sources. We investigated the use of a multi-species source arrangement (192Ir with 125I) for treatment in interstitial prostate brachytherapy. The algorithm utilizes an "adjoint ratio," which provides a means of ranking source positions and is the criterion for the Greedy Heuristic optimization. Three cases were compared, each using 0.4 mCi 125I seeds: case I is the base case using 125I alone, case II uses 0.12 mCi 192Ir seeds mixed with 125I, and case III uses 0.25 mCi 192Ir mixed with 125I. Both multi-species cases result in lower exposure of the urethra and central prostate region. Compared with the base case, the exposure to the rectum and normal tissue increases by a significant amount for case III as compared with the increase in case II, signifying the effect of slower dose falloff rate of higher energy gammas of 192Ir in the tissue. The number of seeds and needles decreases in both multi-species cases, with case III requiring fewer seeds and needles than case II. Further, the effect of 192Ir on uniformity was investigated using the 0.12 mCi 192Ir seeds in multi-species implants. An increase in uniformity was observed with an increase in the number of 0.12 mCi 1921r seeds implanted. The effects of prostate size on the evaluation parameters for multi-species implants were investigated using 0.12 mCi 192Ir and 0.4 mCi 125I, and an acceptable treatment plan with increased uniformity was obtained.

Observations on rotating needle insertions using a brachytherapy robot.

A robot designed for prostate brachytherapy implantations has the potential to greatly improve treatment success. Much of the research in robotic surgery focuses on measuring accuracy. However, there exist many factors that must be optimized before an analysis of needle placement accuracy can be determined. Some of these parameters include choice of the needle type, insertion velocity, usefulness of the rotating needle and rotation speed. These parameters may affect the force at which the needle interacts with the tissue. A reduction in force has been shown to decrease the compression of the prostate and potentially increase the accuracy of seed position. Rotating the needle as it is inserted may reduce frictional forces while increasing accuracy. However, needle rotations are considered to increase tissue damage due to the drilling nature of the insertion. We explore many of the factors involved in optimizing a brachytherapy robot, and the potential effects each parameter may have on the procedure. We also investigate the interaction of rotating needles in gel and suggest the rotate-cannula-only method of conical needle insertion to minimize any tissue damage while still maintaining the benefits of reduced force and increased accuracy.

18F-labeled resin microspheres as surrogates for 90Y resin microspheres used in the treatment of hepatic tumors: a radiolabeling and PET validation study.

(90)Y-labeled resin microspheres (SIR-Spheres) are currently used to treat patients with primary and metastatic solid liver tumors. This treatment is typically palliative since patients have exhausted all other standard treatment options. Improving the quality of life and extending patient survival are typical benchmarks for tracking patient response. However, the current method for predicting microsphere biodistributions with (99m)Tc-labeled macroaggregated albumin (MAA) does not correlate well with patient response. This work presents the development of a new (18)F-labeled resin microsphere to serve as a surrogate for the treatment microsphere and to employ the superior resolution and sensitivity of positron emission tomography (PET). The (18)F microsphere biodistributions were determined in a rabbit using PET imaging and histological review. The PET-based uptake ratio was shown to agree with the histological findings to better than 3%. In addition, the radiolabeling process was shown to be rapid, efficient and relatively stable in vivo.

A new internal pair production branching ratio of 90Y: the development of a non-destructive assay for 90Y and 90Sr.

(90)Y is utilized as a therapeutic radioisotope in radiolabeled monoclonal antibodies and in microspheres for targeted radiation therapy of the liver. Currently, the widely used dose calibrator assay of (90)Y can have uncertainties exceeding +/-10%. A non-destructive assay using spectroscopy is possible by reducing the currently published uncertainty (+/-12%) in the internal pair production branching ratio for the 0(+)-0(+) transition of (90)Zr. A high-purity germanium detector was used to determine the branching ratio to be (31.86+/-0.47) x 10(-6).

Innovations and advances in brachytherapy.

The treatment of cancer with radioactive sources using topical molds and intracavitary radium showed the efficacy of brachytherapy long before external radiation therapy became common practice. Brachytherapy is progressing in several clinical directions that reflect technological innovation as well as changes in medical care which combine to provide significant advances in the practice of brachytherapy today. A major change in brachytherapy, the development of high intensity sources, promoted clinical and technologic innovations in high dose-rate brachytherapy. Pulse dose-rate brachytherapy is the use of these sources to treat a target by using pulses of radiation for several minutes each hour with the same overall time and total dose as low dose-rate treatment. Recent novel approaches of using radiotherapy for prevention of restenosis in coronary and peripheral vessels has interested laboratory and clinical researchers. Most of the work toward new source material for brachytherapy centers around intravascular applications. Technology to support brachytherapy continues to advance rapidly. The interaction between images from diverse modalities and the various phases of the treatment planning is the basis of enhanced treatment planning procedures. Optimization in brachytherapy entails calculating the source strengths or source dwell times to satisfy a set of dose criteria to achieve the best dose distribution for a brachytherapy implant. Progress in computerization and calculation modeling has promoted this technical advance. Education and training in brachytherapy indications and techniques is mandatory to maintain high standards of brachytherapy practice.

The transit dose component of high dose rate brachytherapy: direct measurements and clinical implications.

PURPOSE: To measure the transit dose produced by a moving high dose rate brachytherapy source and assess its clinical significance. METHODS AND MATERIALS: The doses produced from source movement during Ir-192 HDR afterloading were measured using calibrated thermoluminescent dosimeter rods. Transit doses at distances of 0.5-4.0 cm from an endobronchial applicator were measured using a Lucite phantom accommodating 1 x 1 x 6 mm thermoluminescent rods. Surface transit dose measurements were made using esophageal and endobronchial catheters, a gynecologic tandem, and an interstitial needle. RESULTS: No difference was detected in thermoluminescent dosimeter rod responses to 4 MV and Ir-192 spectra (427 nC/Gy) in a range of dose between 2 and 300 cGy. The transit dose at 0.5 cm from an endobronchial catheter was 0.31 cGy/(Curie-fraction) and followed an inverse square fall-off with increasing distance. Surface transit doses ranged from 0.38 cGy/(Curie-fraction) for an esophageal catheter to 1.03 cGy/(Curie-fraction) for an endobronchial catheter. Source velocity is dependent on the interdwell distance and varies between 220-452 mm/sec. A numeric algorithm was developed to calculate total transit dose, and was based on a dynamic point approximation for the moving high dose rate source. This algorithm reliably predicted the empirical transit doses and demonstrated that total transit dose is dependent on source velocity, number of fractions, and source activity. Surface transit doses are dependent on applicator diameter and wall material and thickness. Total transit doses within or outside the desired treatment volume are typically < 100 cGy, but may exceed 200 cGy when using a large number of fractions with a high activity source. CONCLUSION: Current high dose rate brachytherapy treatment planning systems calculate dose only from source dwell positions and assume a negligible transit dose. Under certain clinical circumstances, however, the transit dose can exceed 200 cGy to tissues within and outside the prescribed treatment volume. These additional, unrecognized doses could increase potential late tissue complications, as predicted by the linear quadratic model. To enhance the clinical safety and accuracy of high dose rate brachytherapy, total transit dose should be included in calculated isodose distributions. Significant transit doses to tissues outside the treatment volume should be documented.

Sequential comparison of low dose rate and hyperfractionated high dose rate endobronchial radiation for malignant airway occlusion.

A pilot trial (S2) was conducted at the University of Wisconsin to determine the feasibility, efficacy, and toxicity of hyperfractionated high dose rate endobronchial radiation. To avoid multiple bronchoscopies, an optimized hyperfractionated schema was derived from the linear-quadratic model. Utilizing a single bronchoscopy, 31 patients with malignant airway occlusion received 4 Gy x 4 fractions over 2 days at 2 cm from source center using a high dose rate remote afterloader. Response and morbidity were compared to a previous trial (S1) in which 66 patients were treated with conventional low dose rate endobronchial radiation. Response was assessed by change in performance status, symptom resolution, percent of lifetime rendered symptom-free or improved, and radiographic reaeration. These parameters were highly comparable between the two groups. The mean ECOG performance status improved from 2.2 to 1.8 for S1 and 2.1 to 1.6 for S2; symptom improvement or resolution was noted in 78% for S1 and 79% for S2; lifetime rendered symptom-free or improved was 54% for S1 and 57% for S2; and the overall radiographic response rate was 78% for S1 and 85% for S2. The overall incidence of fistulae was 7/101. We conclude that endobronchial radiation is an effective and safe modality for palliation, and hyperfractionated high dose rate endobronchial radiation achieves responses similar to low dose rate endobronchial radiation with a similar complication rate.

A new re-entrant ionization chamber for the calibration of iridium-192 high dose rate sources.

A re-entrant (well-type) ionization chamber has been designed and fabricated at the University of Wisconsin for use with iridium-192 high dose-rate (HDR) remote after-loading brachytherapy devices. The chamber was designed to provide an ionization current of about 10(-8) ampere with a nominal 10 curie iridium-192 source. A narrow opening is provided into the sensitive volume of the chamber to insert a Nucletron MicroSelectron catheter, or catheters with similar diameters from other HDR manufacturers. The chamber exhibits a flat response (+/- 0.1%) for any source position within +/-4 mm of the chamber center. A 300 volt chamber bias yields a 99.96% ion collection efficiency. The chamber is capable of being calibrated directly with an iridium-192 source which has in turn been calibrated with thimble-type ion chambers. Reproducibility for readings in the current mode for 10 consecutive insertions of the MicroSelectron iridium-192 HDR source is within 0.02% or less. Two thimble chambers calibrated by the U.S. National Institute of Standards and Technology provide calibration traceability of iridium-192 HDR sources and re-entrant chambers to a primary national standards laboratory. Results of activity measurements of 6 commercial iridium-192 HDR sources are reported.

Radiographic visualization of vaginal cylinders in gynecologic high dose rate brachytherapy.

PURPOSE: To develop a marker system allowing an accurate determination of vaginal applicator dimensions and geometry from a radiograph. METHODS AND MATERIALS: The markers consist of two sets of gold seeds embedded into each cylinder identifying the cylinder diameter, and a thin stainless steel disk interposed between adjacent cylinders identifying their interface. An evaluation of the dosimetric properties of the markers was undertaken. An applicator was assembled using four cylinders (4 cm diameter) surrounding a stainless steel uterine tandem with a stainless steel disk 0.05 mm thick and 3.6 cm in diameter interposed between each consecutive pair of cylinders. The assembly was placed on a film and an Ir-192 high dose rate source was programmed to a single dwell position within the applicator. The markers were removed and a second film was exposed with the same dwell position and time. This procedure was repeated with various dwell positions along the applicator. A scanning densitometer was used to measure the density profiles and isodensity distributions of each film. RESULTS: The optical density profiles and isodensity distributions with and without the markers in place were identical for all source dwell positions except when the source was centered in the plane of one of the stainless steel disks, where a maximum decrease of less than 2% in the dose rate was measured. The disks had no effect on the profiles measured along axes more than 2 cm from the projection of the applicator central axis on the film. CONCLUSION: The markers provide geometrical information about the position of the applicator relative to the anatomy necessary for optimized treatment planning. Slight dose perturbations resulting from the markers do occur, but only for dwell positions that center the source in the plane of a disk, and even then only at points very close to the disk. The markers can therefore be ignored from a dosimetric point of view.

The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for carcinoma of the cervix.

PURPOSE: This report presents guidelines for using high-dose-rate (HDR) brachytherapy in the management of patients with cervical cancer, taking into consideration the current availability of resources in most institutions. METHODS: Members of the American Brachytherapy Society (ABS) with expertise in HDR brachytherapy for cervical cancer performed a literature review, supplemented their clinical experience to formulate guidelines for HDR brachytherapy of cervical cancer. RESULTS: The ABS strongly recommends that definitive irradiation for cervical carcinoma must include brachytherapy as a component. Each institution should follow a consistent treatment policy when performing HDR brachytherapy, including complete documentation of treatment parameters and correlation with clinical outcome, such as pelvic control, survival, and complications. The goals are to treat Point A to at least a total low-dose-rate (LDR) equivalent of 80-85 Gy for early stage disease and 85-90 Gy for advanced stage. The pelvic sidewall dose recommendations are 50-55 Gy for early lesions and 55-65 Gy for advanced ones. The relative doses given by external beam radiation therapy (EBRT) vs. brachytherapy depend upon the initial volume of disease, the ability to displace the bladder and rectum, the degree of tumor regression during pelvic irradiation, and institutional preference. As with LDR brachytherapy, every attempt should be made to keep the bladder and rectal doses below 80 Gy and 75 Gy LDR equivalent doses, respectively. Interstitial brachytherapy should be considered for patients with disease that cannot be optimally encompassed by intracavitary brachytherapy. While recognizing that many efficacious HDR fractionation schedules exist, some suggested dose and fractionation schemes for combining the EBRT with HDR brachytherapy for each stage of disease are presented. These recommendations are intended only as guidelines, and the suggested fractionation schemes have not been thoroughly tested. The responsibility for the medical decisions ultimately rests with the treating radiation oncologist. CONCLUSION: Guidelines are established for HDR brachytherapy for cervical cancer. Practitioners and cooperative groups are encouraged to use these guidelines to formulate their treatment and dose-reporting policies. These guidelines will be modified, as image-based treatment becomes more widely available.

Impact of "optimized" treatment planning for tandem and ring, and tandem and ovoids, using high dose rate brachytherapy for cervical cancer.

PURPOSE: Different treatment techniques are used in high dose rate (HDR) remote afterloading intracavitary brachytherapy for uterine cervical cancer. We have investigated the differences between "optimized" and "nonoptimized" therapy using both a tandem and ring (T/R) applicator, and a tandem and ovoids (T/O), applicator. METHODS AND MATERIALS: HDR afterloading brachytherapy using the Madison System for Stage IB cervical cancer was simulated for 10 different patients using both a T/R applicator and a T/O applicator. A treatment course consists of external beam irradiation and five insertions of HDR afterloading brachytherapy. Full dosimetry calculations were performed at the initial insertion for both applicators and used as a reference for the following four insertions of the appropriate applicator. Forty dosimetry calculations were performed to determine the dose delivered to Point M (similar to Point A), Point E (obturator lymph nodes), vaginal surface, bladder, and rectum. "Optimized" doses were specified to Point M and to the vaginal surface. "Nonoptimized" doses were specified to Point M only. Using the linear-quadratic equation, calculations have been performed to convert the delivered dose using HDR to the biologically equivalent doses at the conventional low dose rate (LDR) at 0.60 Gy/h. RESULTS: Major differences between "optimized" and "nonoptimized" LDR equivalent doses were found at the vaginal surface, bladder, and rectum. Overdoses at the vaginal surface, bladder, and rectum were calculated to be 208%, nil, and 42%, respectively, for the T/R applicator with "nonoptimization." However, for the T/O applicator, the overdoses were smaller, being nil, 32%, and 27%, respectively, with "nonoptimization." CONCLUSION: Doses given in high dose rate intracavitary brachytherapy border on tissue tolerance. "Optimization" of either applicator decreases the risk of a dose that may have potential for complications. Optimization of a tandem and ovoids best ensures that the doses are not diminished at the treatment sites, and that the potential for overdose is reduced.

A comparison of the efficacy and complication rates of low dose-rate versus high dose-rate brachytherapy in the treatment of uterine cervical carcinoma.

PURPOSE: To compare the outcome and complication rates for treatment of uterine cervical carcinoma with low dose-rate (LDR) vs. high dose-rate (HDR) brachytherapy at the University of Wisconsin Comprehensive Cancer Center (UWCCC). METHODS AND MATERIALS: One-hundred ninety-eight evaluable patients with cervical carcinoma, Stages IB to IIIB, treated with curative intent with a combination of megavoltage teletherapy and LDR brachytherapy from 1977 to 1988 were the subject of an initial review. In 1989, a HDR treatment program was initiated where all patients with cervical carcinoma were subsequently treated with a combination of HDR brachytherapy and teletherapy. Using the linear-quadratic model (LQ), the dose and schedule of HDR brachytherapy and teletherapy were designed to give similar tumor control and late effects as LDR therapy. Technically, the HDR schedule required meticulous attention to treatment geometry to limit severe late effects. Forty patients treated with the HDR program with 2-4 year follow-up were reviewed and compared to the previous LDR patient group. The LDR and HDR treatment groups were comparable with regards to age, weight, stage distribution, bulk of disease, and histology. RESULTS: No significant difference in survival was found between the LDR and HDR groups with 3-year actuarial overall survival being 66% and 77%, respectively. Three-year actuarial pelvic control rates were similar at 80% and 77% for the LDR and HDR groups, respectively. No significant difference in late treatment complications requiring hospitalization or surgery was found between the two treatment groups with a complication rate of 10% (20/198) for the LDR patients and 2.5% (1/40) for the HDR patients. CONCLUSION: As predicted by our LQ calculations, treatment results for LDR and HDR brachytherapy were similar with respect to survival, pelvic control and late complications in the treatment of cervical carcinoma. The HDR brachytherapy program at the UWCCC appears to be a safe and effective alternative to LDR therapy in the treatment of cervical carcinoma.

High dose rate intracavitary brachytherapy for carcinoma of the cervix: the Madison system: II. Procedural and physical considerations.

The loss in therapeutic ratio accompanying a conversion from low dose-rate (LDR) to high dose-rate (HDR) intracavitary brachytherapy (ICR) requires increased attention to the precision and accuracy of dose distribution calculations and treatment delivery. While the HDR-ICR treatment unit allows better custom-tailored dose distributions compared to LDR, it also requires more attention to detail to achieve the distribution desired. Because the relative biological effectiveness of different isodose levels in a dose distribution varies with the absolute dose (as described in Part 1 of this article), the relative dose distribution used with LDR must be modified for HDR to produce the same expected biological effect. Because of the difference in the radiobiology and physical positioning, simply duplicating applications as performed with LDR misses opportunities for dose distribution improvement as well as opens possibilities for significant complications. Due to differences in positioning the applicator (e.g., retraction of the cervix low in the pelvis instead of packing the applicator high), traditional definitions of points of interest (such as point A) apply poorly with HDR-ICR, compelling new systems of dose specification. With HDR-ICR, irreparable mistakes can happen very quickly, and quality assurance for the treatment plan and calculated dwell times prove much more important than with LDR. Key features of the dose distribution and constant relationships involving doses and dwell times help screen planned treatments for mistakes. This paper details the procedural and physical consideration of the Madison system for HDR-ICR brachytherapy for carcinoma of the cervix.

High dose rate intracavitary brachytherapy for carcinoma of the cervix: the Madison system: I. Clinical and radiobiological considerations.

The decision to use five high dose rate intracavitary (HDR-ICR) insertions at weekly intervals for invasive carcinoma of the cervix treated at the University of Wisconsin Comprehensive Cancer Center (UWCCC) was made clinically. It was based on practical considerations and on previous clinical experience worldwide which showed that between 2 and 16 insertions have been used with apparently acceptable results. Although radiobiological considerations favor a large number of small doses, such a large number of HDR-ICR insertions is not clinically practical. Our strategy was to keep the biological effects of external beam and intracavitary insertions in the same ratio as used on a large series of patients treated here with low dose rate (LDR) therapy. This means keeping the same external beam treatment scheme and finding high dose rate (HDR) doses that are biologically equivalent to the previous LDR therapy, as far as possible. External beam and HDR intracavitary dose schedules for the Madison System of treating cervical carcinoma are described in detail. Because there is more repairable damage in late-reacting normal tissues, there is a bigger loss of sparing in these tissues than in tumors when changing from LDR to HDR, so total doses should be reduced more for equal late complications than for equal tumor control. The clinical decision was made to aim at equal tumor control. The possible increase in late complications has to be avoided by reducing the doses to critical normal tissues using extremely careful anatomic positioning of the HDR sources. Critical normal tissues must be kept further away from the radiation sources so that their doses are about 20% lower than with LDR geometry. This requires an extra separation of some millimeters depending on the anatomy and geometry of the individual insertion. The strategy is that the unfavourable radiobiological effects of a few large fractions must be counteracted by better physical dose distributions with HDR-ICR than with the previous LDR insertions. These good distributions are obtainable with the short exposures at HDR.

Postoperative vaginal cuff irradiation using high dose rate remote afterloading: a phase II clinical protocol.

PURPOSE: In September 1989, a postoperative Phase II high dose rate (HDR) brachytherapy protocol was started for International Federation of Gynecology and Obstetrics (FIGO) Stage I endometrial adenocarcinoma. This review reports the overall survival, local control, and complication rates for the initial 63 patients treated in this Phase II study. METHODS AND MATERIALS: High dose rate brachytherapy was delivered using an Iridium-192 HDR remote afterloader. Sixty-three patients were entered into the Phase II protocol, each receiving two vaginal cuff treatments 1 week apart (range 4-12 days) with vaginal ovoids (diameter 2.0-3.0 cm). No patient received adjuvant external beam radiation. A dose of 32.4 Gy in two fractions was prescribed to the ovoid surface in 63 patients. The first three patients treated at our institution received 15, 16.2, and 29 Gy, respectively, to determine acute effects. RESULTS: At a median follow-up of 1.6 years (range 0.75-4.3 years) no patient has developed a vaginal cuff recurrence. One regional recurrence (1.6%) occurred at 1.2 years at the pelvic side wall. This patient is alive and without evidence of disease 7 months after completion of salvage irradiation, which resulted in the only vaginal stenosis (1.6%). Fourteen patients (22%) experienced vaginal apex fibrosis by physical exam, which was clinically symptomatic in four patients. Two patients reported stress incontinence; however, these symptoms were noted prior to their HDR therapy. One patient died 2.4 years after HDR therapy due to cardiovascular disease without evidence of cancer at autopsy. CONCLUSION: Preliminary results of our phase II HDR vaginal cuff protocol for postoperative FIGO Stage IA, Grade 3 or Stage IB, Grade 1-2 patients demonstrate that 32.4 Gy in two fractions is well tolerated by the vaginal cuff mucosa. Local control appears comparable to our prior experience and others with low dose rate (LDR) brachytherapy. Additional patient accrual and further follow-up will better determine the late morbidity, local control, and overall survival of these patients.

A solid water pelvic and prostate phantom for imaging, volume rendering, treatment planning, and dosimetry for an RTOG multi-institutional, 3-D dose escalation study. Radiation Therapy Oncology Group.

PURPOSE: With increased interest in 3-D conformal radiation therapy and dose escalation, it is necessary to provide advanced techniques to assure quality in treatment delivery. Multi-institutional trials for these newer treatment techniques require methods of verifying the consistency of treatments between the participating institutions. For this reason, a phantom was designed to address the quality and consistency of Radiation Therapy Oncology Group (RTOG) 3-D prostate treatment protocol. METHODS AND MATERIALS: A solid water pelvic and prostate phantom for imaging, volume rendering, treatment planning, and dosimetry applications for performing comprehensive quality assurance has been designed and fabricated. Its configuration was based upon CT slices obtained from a patient study. Individual slices were machined with corresponding contours of the prostate, bladder, rectum, and the left and right femurs. Most of the phantom is made of solid water (Gammex/RMI, Middleton, WI), while the femurs are made of bone-equivalent material. The CT numbers from patient images were used to adjust the solid water composition within the organ volumes, providing image contrast from the remainder of the phantom. Cylindrical insertion grooves are machined in the phantom to allow placement of ionization chambers and thermal luminal dosimeters (TLDs) for dosimetry applications. During imaging, the cavities are filled with rods fabricated from solid water material. RESULTS: The phantom is being used to evaluate the consistency of a range of processes in radiation therapy simulation, planning, and delivery of 3-D-based treatments for prostate cancer. CONCLUSION: The ultimate study objective is to use the phantom to evaluate the accuracy and consistency of treatments delivered by institutions participating in national collaborative clinical trials involving 3-D conformal dose escalation.

The adverse effect of treatment prolongation in cervical carcinoma.

PURPOSE: Proliferation of surviving tumor clonogens during a course of protracted radiation therapy may be a cause of local failure in cervical carcinoma. The effect of total treatment time was analyzed retrospectively in relation to pelvic control and overall survival for squamous cell carcinomas of the uterine cervix. METHODS AND MATERIALS: Two hundred and nine patients (Stage IB-IIIB) treated with a combination of external beam and low dose rate intracavitary irradiation were evaluable for study. Multivariate analysis and Kaplan-Meier statistical methods were used to determine the effect of treatment time on pelvic control and survival at 5 years. RESULTS: The median treatment duration was 55 days. For all stages combined, the 5-year survival and pelvic control rates were significantly different with treatment times < 55 days vs. > or = 55 days: 65 and 54% (p = 0.03), 87 and 72% (p = 0.006), respectively. By stage, a shorter treatment duration (i.e., < 55 days vs. > or = 55 days) was significant for 5-year overall survival and pelvic control for Stages IB/IIA and III, but not for Stage IIB: Stage IB/IIA (81 and 67%, 96 and 84%), Stage III disease (52 and 42%, 76 and 55%) and Stage IIB (43 and 50%, 74 and 80%, respectively). Survival decreased 0.6%/day and pelvic control decreased 0.7%/day for each additional day of treatment beyond 55 days for all stages of disease. Additionally, significant late complications were not influenced by treatment time. CONCLUSION: These results suggest that prolongation of treatment time is associated with decreased local control and survival in patients with cervical carcinoma. This is consistent with emerging data from other institutions. Therapeutic implications include avoidance of unnecessary treatment breaks, the design of fractionation schemes that decrease treatment duration, and possibly the use of tumor cytostatic drugs during conventional radiation.

Evaluation of the reconstruction of brachytherapy implants in three-dimensions from stereo radiographs.

The precision and the accuracy of the stereo-shift method for reconstruction of brachytherapy implants were evaluated. Analysis of shift films was performed by measuring the coordinates of the seeds in an experimental set-up in the laboratory, by manually calculating the coordinates of the seeds from the projection distances on the stereo-shift radiographs, and by using a computer-aided treatment planning system. The resultant reconstructed coordinates agreed well with each other. The uncertainties in precision for the coordinates were expressed as the standard deviation of the measurements. The standard deviation of the computer and manual measurements agreed well with predicted values by an analysis of the random uncertainties in the reconstruction parameters. The uncertainties were within 0.2 mm for the coordinates parallel to the plan of the film and were within 0.4 mm for the coordinate perpendicular to the plane of the shift film. The uncertainties in the accuracy of the reconstruction were compared with the values obtained in clinical practice as well as with the values reported in the literature. Suggestions are made to improve the accuracy.