Judith A. Stitt

Code of practice for brachytherapy physics: Report of the AAPM Radiation Therapy Committee Task Group No. 56

Recommendations of the American Association of Physicists in Medicine (AAPM) for the practice of brachytherapy physics are presented. These guidelines were prepared by a task group of the AAPM Radiation Therapy Committee and have been reviewed and approved by the AAPM Science Council.

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.

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.

Late injury of cancer therapy on the female reproductive tract

The purpose of this article is to review the late effects of cancer therapy on the female reproductive tract. The anatomic sites detailed are the vulva, vagina, cervix, uterus, fallopian tubes, and ovaries. The available pathophysiology is discussed. Clinical syndromes are presented. Tolerance doses of irradiation for late effects are rarely presented in the literature and are reviewed where available. Management strategies for surgical, radiotherapeutic, and chemotherapeutic late effects are discussed. Endpoints for evaluation of therapeutic late effects have been formulated utilizing the symptoms, objective, management, and analytic (SOMA) format. Late effects on the female reproductive tract from cancer therapy should be recognized and managed appropriately. A grading system for these effects is presented. Endpoints for late effects and tolls for the evaluation need to be further developed.

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.

Consensus guidelines for high dose rate remote brachytherapy in cervical, endometrial, and endobronchial tumors*

PURPOSE A large number of medical centers have recently instituted the use of High Dose-Rate Afterloading Brachytherapy (HDRAB). There is wide variation in treatment regimens, techniques, and dosimetry being used and there are no national standard protocols or guidelines for optimal therapy. METHODS AND MATERIALS The Clinical Research Committee (CRC) of the American Endocurietherapy Society (AES) met to formulate consensus guidelines for HDRAB in cervical, endometrial, and endobronchial tumors. CONCLUSION Each center is encouraged to follow a consistent treatment policy in a controlled fashion with complete documentation of treatment parameters and outcome including efficacy and morbidity. Until further clinical data becomes available, the linear quadratic model can be used as a guideline to formulate a new HDR regimen exercising caution when changing from a Low Dose Rate (LDR) to a HDRAB regimen. The treatments should be fractionated as much as practical to minimize long term morbidity. As more clinical data becomes available, the guidelines will mature and be updated by the Clinical Research Committee of the AES.

Analysis of treatment delivery errors in brachytherapy using formal risk analysis techniques

PURPOSE To identify hazardous situations in treatments, analyze the nature of errors committed, and assess the value of several analysis techniques. MATERIALS AND METHODS The study applied several risk analysis techniques to brachytherapy events (misadministrations) reported to the U.S. Nuclear Regulatory Commission and the International Atomic Energy Agency. RESULTS (1) Events usually have multiple causes. (2) Failure to consider human performance in the design of equipment led to a large fraction of the events. (3) Verification procedures often were ineffectual. (4) Many events followed the failure of persons involved to detect that the situation was abnormal, often even though many indications pointed to that fact. Once the event was identified, the response often included actions appropriate for normal conditions, but inappropriate for the conditions of the event. (5) Events tended to happen most with actions having the least time available. (6) Lack of training and procedures covering unusual conditions frequently contributed to events. (7) New procedures or new persons joining a case in the middle present increased hazards. CONCLUSIONS Risk analysis tools common in industry provide useful information for error reduction in medical settings, although not as effectively, and modification of such techniques could improve their efficacy.

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.

Resource utilization. High dose rate versus low dose rate brachytherapy for gynecologic cancer.

A comparative analysis of anesthesia use, perioperative morbidity and mortality, capital, and treatment cost of high dose rate versus low dose rate intracavitary brachytherapy for gynecologic malignancy is presented. To assess current anesthesia utilization, application location, and high dose rate afterloader availability for gynecologic brachytherapy in private and academic practices, a nine-question survey was sent to 150 radiotherapy centers in the United States, of which 95 (63%) responded. Of these 95 respondents, 95% used low dose rate brachytherapy, and 18% possessed high dose rate capability. General anesthesia was used in 95% of programs for tandem + ovoid and in 31% for ovoids-only placement. Differences among private and academic practice respondents were minimal. In our institution, a cost comparison for low dose rate therapy (two applications with 3 hospital days per application, operating and recovery room use, spinal anesthesia, radiotherapy) versus high dose rate treatment (five outpatient departmental applications, intravenous anesthesia without an anesthesiologist, radiotherapy) revealed a 244% higher overall charge for low dose rate treatment, primarily due to hospital and operating room expenses. In addition to its ability to save thousands of dollars per intracavitary patient, high dose rate therapy generated a “cost-shift,” increasing radiotherapy departmental billings by 438%. More importantly, perioperative morbidity and mortality in our experience of 500+ high dose rate applications compared favorably with recently reported data using low dose rate intracavitary treatment. Capital investment, maintenance requirements, and depreciation costs for high dose rate capability are reviewed. Application of the defined “revenue-cost ratio” formula demonstrates the importance of high application numbers and consistent reimbursement for parity in high dose rate operation. Logically, inadequate third-party reimbursement (e.g., Medicare) reduces high dose rate parity and threatens the future availability of high dose rate technology.