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Purpose: To examine the acute urinary toxicity following transperineal prostate implant using a modified Quimby loading method with regard to time course, severity, and factors that may be associated with a higher incidence of morbidity., Methods and Materials: One hundred thirty-nine patients with prostate adenocarcinoma treated with brachytherapy from 1997 through 1999 had follow-up records available for review. Patients considered for definitive brachytherapy alone included those with prostate specific antigen (PSA) < or = 6, Gleason score (GS) < or = 6, clinical stage < T2b, and prostate volumes generally less than 40 cc. Patients with larger prostate volumes were given neoadjuvant antiandrogen therapy. Those with GS > 6, PSA > 6, or Stage > T2a were treated with external beam radiation therapy followed by brachytherapy boost. Sources were loaded according to a modified Quimby method. At each follow-up, toxicity was graded based on a modified RTOG urinary toxicity scale., Results: Acute urinary toxicity occurred in 88%. Grade I toxicity was reported in 23%, grade II in 45%, and grade III in 20%, with 14% requiring prolonged (greater than 1 week) intermittent or indwelling catheterization. Overall median duration of symptoms was 12 months. There was no difference in duration of symptoms between patients treated with I-125 or Pd-103 sources (p = 0.71). After adjusting for GS and PSA, multivariate logistic regression analysis showed higher incidence of grade 3 toxicity in patients with larger prostate volumes (p = 0.002), and those with more seeds implanted (p < 0.001). Higher incidence of prolonged catheterization was found in patients receiving brachytherapy alone (p = 0.01), with larger prostate volumes (p = 0.01), and those with more seeds implanted (p < 0.001)., Conclusion: Interstitial brachytherapy for prostate cancer leads to a high incidence of acute urinary toxicity, most of which is mild to moderate in severity. A prolonged need for catheterization can occur in some patients. Patients receiving brachytherapy alone, those with prostate volumes greater than 30 cc, and those implanted with a greater number of seeds have the highest incidence of significant toxicity.

Purpose: To determine if patients with carcinoma of the vulva, with N2/N3 lymph nodes, could undergo resection of the lymph nodes and primary tumor following preoperative chemo-radiation. METHODS AND MATERILAS: Fifty-two patients were entered in the study, but six patients did not meet the criteria of the protocol and were excluded. The remaining 46 patients are the subject of this report. Patients underwent a split course of radiation, 4760 cGy to the primary and lymph nodes, with concurrent chemotherapy, cisplatin/5-FU, followed by surgery., Results: Four patients did not complete the chemo-radiation, because three expired and one refused to complete the treatment. Four patients who completed chemo-radiation did not undergo surgery, because two of them died of non-cancer-related causes, and in the other two patients, the nodes remained unresectable. Following chemo-radiation, the disease in the lymph nodes became resectable in 38/40 patients. Two patients who completed the course of chemo-radiation did not undergo surgery as per protocol because of pulmonary metastasis. One underwent radical vulvectomy and unilateral node dissection and the other radical vulvectomy only. The specimen of the lymph nodes was histologically negative in 15/37 patients. Nineteen patients developed recurrent and/or metastatic disease. The sites of failure were as follows: primary area only, 9; lymph node area only, 1; primary area and distant metastasis, 1; distant metastasis only, 8. Local control of the disease in the lymph nodes was achieved in 36/37 and in the primary area in 29/38 of the patients. Twenty patients are alive and disease-free, and five have expired without evidence of recurrence or metastasis. Two patients died of treatment-related complications., Conclusion: High resectability and local control rates of the lymph nodes were obtained in patients with carcinoma of the vulva with N2/N3 nodes treated preoperatively with chemo-radiation.

Purpose: To determine the feasibility of using preoperative chemoradiotherapy to avert the need for more radical surgery for patients with T3 primary tumors, or the need for pelvic exenteration for patients with T4 primary tumors, not amenable to resection by standard radical vulvectomy., Methods and Materials: Seventy-three evaluable patients with clinical Stage III-IV squamous cell vulvar carcinoma were enrolled in this prospective, multi-institutional trial. Treatment consisted of a planned split course of concurrent cisplatin/5-fluorouracil and radiation therapy followed by surgical excision of the residual primary tumor plus bilateral inguinal-femoral lymph node dissection. Radiation therapy was delivered to the primary tumor volume via anterior-posterior-posterior-anterior (AP-PA) fields in 170-cGy fractions to a dose of 4760 cGy. Patients with inoperable groin nodes received chemoradiation to the primary vulvar tumor, inguinal-femoral and lower pelvic lymph nodes., Results: Seven patients did not undergo a post-treatment surgical procedure: deteriorating medical condition (2 patients); other medical condition (1 patient); unresectable residual tumor (2 patients); patient refusal (2 patients). Following chemoradiotherapy, 33/71 (46.5%) patients had no visible vulvar cancer at the time of planned surgery and 38/71 (53.5%) had gross residual cancer at the time of operation. Five of the latter 38 patients had positive resection margins and underwent: further radiation therapy to the vulva (3 patients); wide local excision and vaginectomy necessitating colostomy (1 patient); no further therapy (1 patient). Using this strategy of preoperative, split-course, twice-daily radiation combined with cisplatin plus 5-fluorouracil chemotherapy, only 2/71 (2.8%) had residual unresectable disease. In only three patients was it not possible to preserve urinary and/or gastrointestinal continence. Toxicity was acceptable, with acute cutaneous reactions to chemoradiotherapy and surgical wound complications being the most common adverse effects., Conclusion: Preoperative chemoradiotherapy in advanced squamous cell carcinoma of the vulva is feasible, and may reduce the need for more radical surgery including primary pelvic exenteration.

Purpose: Intracavitary dose prescription for cancer of the uterine cervix has been based on the use of plane orthogonal films. Computed tomography (CT) and magnetic resonance imaging can provide three-dimensional (3D) anatomic information with which more sophisticated treatment planning can be carried out. This work describes a new tandem and ovoids design that permits modern 3D dosimetry and has the same placement flexibility for the physician as the applicators currently being used., Methods and Materials: The external shape of the Fletcher-Suit-Delclos (FSD) minicolpostat tandem and ovoids system has been used as a model to build a prototype of a new applicator. The prototype colpostats are constructed out of aluminum and steel. The tandems are made of aluminum. The Fletcher shields are eliminated. A new method of using tungsten for dose attenuation and shielding has been designed. Longitudinal alignment of the tungsten shields makes the new system possible. This applicator is CT-compatible., Results: Dose calculations for the new design are compared to a commercial version of the FSD applicator. Both the aluminum prototype and a simple extension of the prototype to a plastic applicator system are considered. It is shown that the principal difference in dose is that the dose is reduced in the region inferior to the center of the ovoids. All configurations (plastic caps on or off) are equivalently shielded for the new device. In addition, an intermediate mini-ovoid configuration can be used clinically via the introduction of a D-shaped cap. The latter reduces the high dose to the vaginal mucosal surfaces., Conclusion: For a single ovoid, a comparison of dose with the FSD shows differences; however, the difference in dose is insignificant when the complete applicator, tandem, and ovoids are compared. With this new applicator, it is now possible to accumulate very accurate and detailed 3D dose-distribution data for the critical structures and other points of interest in the vicinity of the applicator. These data will permit future analysis of the correlation of dose and outcome for carcinoma of the cervix.

Purpose: A review of the Patterns of Care Studies Process Survey data on carcinoma of the cervix conducted on patients in 1978, 1983, and 1988-89 was carried out to identify changes or trends in the demographics, evaluation, and treatment that might have occurred over this time period., Methods and Materials: Patterns of Care Studies conducted surveys on patients treated by radiation therapy for cervical carcinoma in 1978, 1983, and 1988-89. These surveys have compiled demographic and treatment data on a total of 993 patients. There is outcome data for the 1978 and 1983 surveys, but not for the 1988-89 survey because follow-up has not been collected yet. The demographic and treatment delivery data on all three surveys has been reviewed and analyzed and is the subject of this study., Results: There was no difference in the age distribution at the time of diagnosis of the patients in these surveys. The percentage of black patients remained constant in the three surveys, 19%, 17%, and 21%, respectively. The percentage of white patients was 76%, 78%, and 67%, but that of nonwhite/nonblack patients was 3%, 4%, and 12% (p < 0.001). The distribution of patients by stage was similar in the first two surveys. In the third survey, there was a decrease in the percentage of patients with Stage IA and IB (first = 35%; second = 38%; third = 29%) with a concurrent increase in Stage IIIA and IIIB patients (first = 20%; second = 18%; third = 26%). The surveys showed a major change in the pretreatment evaluation tests used. There was a progressive decrease in the use of intravenous pyelogram (IVP) (86 to 42%), barium enema (58 to 32%), cystoscopy for patients Stage IIB and higher (64 to 52%), and lymphangiography (18 to 14%). The use of abdominal or pelvic computed tomography dramatically increased from 6 to 70% between the first and third surveys. The use of 60Co units decreased from 35 to 2% from the first to the third survey [6 to 0% for short source-surface distance (SSD) 60Co units]. Point dose calculations for the intracavitary therapy increased from 78% in the 1978 survey to 95% in the third survey. As determined by the total dose delivered to the paracentral points, more patients (75.1%) were treated according to the Patterns of Care recommended guidelines in the 1988-89 survey than in the 1983 survey (63.6%). Chemotherapy was given to 12% of the patients undergoing radiation therapy during the period of the third survey, but these data are not available for the first and second surveys., Conclusion: Review of the Carcinoma of the Cervix Patterns of Care studies discloses significant changes in the demographics, patient evaluation, and radiation therapy techniques during the period of the studies. The potential impact of these changes on treatment outcome cannot be determined at this time until longterm follow-up for the 1988-89 survey is available, but improvements in the processes of care should lead to improvements in outcome.

Purpose: To determine the efficacy of radiotherapy (RT) in patients with an isolated elevation of prostate specific antigen (PSA) after radical prostatectomy (RP)., Methods and Materials: Between November 1987 and May 1993, 53 patients with adenocarcinoma of the prostate were referred for pelvic RT for an elevated PSA after RP. No patient had clinically or radiographically apparent local or distant disease, nor had an undergone prior androgen ablation. Patients received a median dose of 61.2 Gy to the prostatic bed. An undetectable PSA was required to be considered disease free (NED). Univariate and multivariate analyses were performed to identify factors predictive of becoming disease free after RT., Results: The median follow-up was 15 months. Of the 53 patients, 16 (30%) became NED after RT and 15 (28%) had a declining (n = 11) or stable (n = 4) PSA at last evaluation. The median time after RT to achieve an undetectable PSA was 9.3 months. At 12 and 24 months, the actuarial disease-free survival was 30 and 23%, respectively; actuarial progression-free survival was 71 and 26%, respectively. By univariate analysis, the last PSA level before RT (i.e., the pre-RT PSA) and an undetectable PSA after RP were significant predictors of becoming NED (p = 0.0001 and 0.04, respectively). However, on multivariate analysis, only the pre-RT PSA remained significant (p = 0.01). The mean pre-RT PSA differed significantly between patients who became NED after RT and those who did not (1.5 +/- 0.2 ng/ml vs. 7.6 +/- 1.6 ng/ml, respectively; p = 0.018). Fourteen of 27 (52%) patients with pre-RT PSA levels < or = 2.5 ng/ml became NED, vs. only 2 of 26 (8%) patients with higher levels. There were no severe acute or late sequelae of RT., Conclusion: Prostatic-bed RT for an elevated serum PSA after RP is most effective in patients with a pre-RT PSA < or = 2.5 ng/ml. Patients with significantly higher PSA values are unlikely to benefit from RT, possibly due to the presence of occult distant metastases. The optimal therapy for this latter group remains to be determined.

From 1984-1990, 143 patients with squamous cell or adenocarcinoma of the esophagus were enrolled in a Phase I/II study of neoadjuvant chemotherapy followed by concurrent chemotherapy plus radiotherapy with or without subsequent esophagectomy. Patients received one cycle of Cisplatin or Carboplatin plus Etoposide for squamous cell carcinoma, or Cisplatin or Carboplatin plus 5FU for adenocarcinoma, followed by two cycles of the same chemotherapy given concurrently with 44-46 Gy over 5 weeks. Operable patients then underwent esophagectomy. Inoperable patients and those with positive surgical margins received additional irradiation (16-18 Gy). Twelve percent of the surgical group received preoperative radiotherapy doses > or = 50 Gy. Seventy-two percent (103) had clinical Stage I-III tumors and 28% (40) were clinical Stage IV (1983 American Joint Committee on Cancer criteria). Only clinical Stage I-III patients were analyzed with respect to patterns of failure. Isolated local failure occurred in 19/103 (18%) of clinical Stage I-III patients. Both local and distant relapse occurred in 15/103 (15%), and distant metastases alone occurred in 25/103 (24%). The 3-year actuarial rates of local and distant failures were 45% and 60%, respectively. Among the clinical Stage I-III patients who underwent surgery (n = 58) versus those who did not (n = 45), the 3-year actuarial local and distant failure rates were 30% versus 60% and 45% versus 45%, respectively. Multivariate analysis was performed to identify significant predictors of local control. For all clinical Stage I-III patients, treatment with surgery (p = 0.001) and with three or more cycles of chemotherapy (p = 0.02) were significant predictors of improved local control. Patients who underwent surgery were significantly younger and had a better performance status than those who did not. The improvement in local control with surgery did not translate into better survival, likely on account of a high operative mortality rate in older patients and those receiving > or = 50 Gy preoperatively. We conclude that local control remains poor with concurrent chemotherapy + radiotherapy for esophageal cancer. The addition of surgery improved local control, but distant metastases remain a problem both in this group of patients as well as those treated without esophagectomy. Efforts to improve local control appear warranted, but it remains to be demonstrated that improved local control translates into improved survival in esophageal cancer because of a high rate of distant metastases in patients whose disease is controlled in the esophagus.

A plastic intracavitary applicator system for the treatment of cancer of the uterine cervix is described. This applicator has a minicolpostat and a mechanism for affixing the tandem to the colpostats. Traditional afterloading refers only to the radioactive source. Both the source and the ovoid shield are afterloaded together in this applicator in contrast to traditional afterloading systems which afterload the source alone. A potential advantage of our applicator system is that it allows high quality CT localization because the sources and shields can be removed and the applicator is made of plastic. The advantages and disadvantages of this variation to the Fletcher system as well as other aspects of applicator design are discussed. An experimentally verified dose calculation method for shielded sources is applied to the design problems associated with this applicator. The dose distribution calculated for a source-shield configuration of the plastic applicator is compared to that obtained with a commercial Fletcher-Suit-Delclos (FSD) applicator. Significant shielding improvements can be achieved for the smallest diameter ovoid, that is, in the minicolpostat. The plastic minicolpostat dose distributions are similar to those produced by the conventional larger diameter colpostats. In particular, the colpostat shielding for rectum and bladder, which is reduced in the metal applicator's minicolpostat configuration, is maintained for the plastic minicolpostat. Further, it is shown that, if desired, relative to the FSD minicolpostat, the mucosa dose can be reduced by a suitable change of the minicolpostat source position.

Patterns of Care Study (PCS) conducted the second survey of carcinoma of the cervix in 1978. The data of this survey are derived from 565 patient questionnaires completed from 120 randomly selected facilities. Through these surveys PCS has set out to establish a profile of the practice of radiation therapy in the United States as well as determine the survival, local control rates, patterns of recurrence, complications, and relationship of these events with dose. This study deals with the patterns and sites of failure and relationship with dose to the paracentral and lateral points previously defined. The breakdown of patients according to the stage was as follows: Stage I = 203, Stage II = 243, Stage III = 115, undertermined = 4. Twenty-three percent of the patients failed within the field of irradiation, whereas 9% failed outside of the irradiated field. The infield failure rate increased as a function of stage from 9% in Stage I to 23% in Stage II and 48% in Stage III. Distant metastasis was the first site of failure in 4% of patients with Stage I, 7% for Stage II, 9% for Stage III, and 6% for the entire group. The cervix and vagina were the first site of recurrence in 20% of the patients. The cervical/vaginal recurrence rate increased as a function of stage from 7% in Stage I to 21% in Stage II, and 37% in Stage III. An analysis of the cervical/vaginal recurrences as a function of the average total dose to the paracentral points showed a decreased recurrence rate as a function of dose within the range of less than 6500 to 7999 cGy. The recurrence rate at 4 years decreased from 34% with a dose of less than 6500 cGy to 14% with a dose of 7500-7999 cGy. Above this dose level, this correlation of dose with recurrence was not observed. This correlation was also absent when the patients were studied according to the stage of the disease. The relationship of parametrial/sidewall failure and average dose to the lateral point was studied also, but no correlation was found except for patients with Stage III disease. The disease-free survival was studied for the entire group of patients and for the different stages as a function of average paracentral dose: less than 7500 cGy, 7500 to 8500 cGy, and greater than 8500 cGy. The disease-free survival was lower for the patients in the less than 7500 cGy group.(ABSTRACT TRUNCATED AT 400 WORDS)

A technique is described for the design and construction of customized templates for transperineal implants and interstitial hyperthermia of pelvic malignancies. The design of the template and the distribution of the transperineal Iridium-192 seed ribbons are based on prior optimization of the dose distribution. The target volume is defined by means of pelvic examination and pertinent radiographic studies including a CT. The pelvic CT study is obtained with a plastic obturator in the rectum or the vagina. The obturator is used as a reference structure for aligning the target contour from each image plane to form a composite 2-dimensional contour of maximum tumor extent in a plane perpendicular to the obturator. Dose distributions are calculated to determine the placement of the Iridium-192 seed ribbons in the template. Laparoscopic guidance is used for actual placement of brachytherapy source needles together with a rectal or vaginal obturator to stabilize the template and to assure that the needle placement conforms with the planned geometry. Dose distributions for 10 consecutive patients calculated for customized templates as well as for five commercially available standard templates show that the customized templates are superior to standard templates in that the planned dose distribution matches the configuration of the target volume and is more uniform than with standard templates.

An analysis has been made of 101 patients treated with radiation therapy for epidermoid carcinoma of the cervix Stage IB (FIGO) from January 1970 through December 1976. The patients were treated with a combination of intracavitary therapy and external beam therapy delivering a total combined dose of 8000 rad to the paracervical areas (Points AR and AL) and 5500 rad to the pelvic lymph nodes (Points IR and IL). The cumulative, disease-free survival at 2, 3 and 5 years was 89%, 87% and 84%. Sixteen failures were recorded in this group of patients, of which 3 were a result of loco-regional disease, 5 loco-regional disease plus distant metastasis and 8 distant metastasis only. The failure rate was greater among the patients who had lesions 4 or more cm in diameter and in patients who received doses of external beam therapy to the whole pelvis of 4000 rad or more. Eighteen patients developed complications; however, one patient had a recto-vaginal and a vesico-vaginal fistula; thus 19 complications were recorded. The complications were divided according to their severity into three groups: Grade I (mild), Grade II (moderate) and Grade III (severe). There were 10 Grade I, 4 Grade II and 5 Grade III complications.

From April 1969 through December 1980, 527 patients with epidermoid carcinoma of the cervix received radical radiation therapy at North Carolina Memorial Hospital (NCMH). The treatment was designed to deliver a combined dose (external beam plus intracavitary) of 7000-8000 cGy to Point A and 5000-6500 cGy to the pelvic lymph nodes depending upon the stage of the disease. The maximum dose to the bladder and to the rectum were calculated from the orthogonal intracavitary placement films with contrast material in these organs. Thirty-three cases of cystitis and fifty-eight cases of proctitis were recorded. The mean bladder dose for the group of patients with cystitis was higher, 6661 +/- 1309 cGy, than that for the patients without cystitis, 6298 +/- 1305 cGy, p = .19. The risk of cystitis increased as a function of bladder dose ranging from 3% for patients receiving less than or equal to 5000 cGy to the bladder to 12% for patients receiving greater than or equal to 8001 cGy to the bladder. A similar correlation was also found for rectal dose and proctitis. The mean rectal dose for the group of patients with proctitis was higher, 6907 +/- 981 cGy, than that for the patients without proctitis, 6381 +/- 1290 cGy, p = .003. The risk of proctitis increased as a function of rectal dose ranging from 2% for patients receiving less than or equal to 5000 cGy to the rectum to 18% for patients receiving greater than or equal to 8001 cGy to the rectum. A study of the severity of the cystitis as a function of bladder dose revealed a relationship between bladder dose and the severity of the complication (Grade I cystitis = 6600 +/- 1318 cGy vs Grade III cystitis = 6856 +/- 853 cGy). A dose-response relationship was found between the rectal dose and the severity of the complication (Grade I proctitis = 6810 +/- 906 cGy vs Grade III proctitis = 6997 +/- 1137 cGy). This relationship was statistically significant, p = .003. While there was no difference in the frequency of cystitis as a function of dose to the whole pelvis, the risk of proctitis did increase with increasing doses of external beam to the whole pelvis. It ranged from 3% for patients who received 2000 cGy or less to the whole pelvis to 14% for patients who received greater than 4000 cGy to the whole pelvis, p = .02.