Survey of current practices from an international task force for gynecological stereotactic ablative radiotherapy.

BACKGROUND: Stereotactic Ablative Radiotherapy (SABR) is an effective treatment that improves local control for many tumours. However, the role of SABR in gynecological cancers (GYN) has not been well-established. We hypothesize that there exists considerable variation in GYN-SABR practice and technique. The goal of this study is to describe clinical and technical factors in utilization of GYN-SABR among 11 experienced radiation oncologists. MATERIALS AND METHODS: A 63 question survey on GYN-SABR was sent to 11 radiation oncologists (5 countries) who have published original research, conducted trials or have an established program at their institutions. Responses were combined and analyzed at a central institution. RESULTS: Most respondents indicated that salvage therapy (non-irradiated or re-irradiated field) for nodal (81%) and primary recurrent disease (91%) could be considered standard options for SABR in the setting of inability to administer brachytherapy. All other indications should be considered on clinical trials. Most would not offer SABR as a boost in primary treatment off-trial without absolute contraindications to brachytherapy. Multi-modality imaging is often (91%) used for planning including PET, CT contrast and MRI. There is a wide variation for OAR tolerances however small bowel is considered the dose-limiting structure for most experts (91%). Fractionation schedules range from 3 to 6 fractions for nodal/primary definitive and boost SABR. CONCLUSIONS: Although SABR has become increasingly standard in other oncology disease sites, there remains a wide variation in both clinical and technical factors when treating GYN cancers. Nodal and recurrent disease is considered a potential indication for SABR whereas other indications should be offered on clinical trials. This study summarizes SABR practices among GYN radiation oncologists while further studies are needed to establish consensus guidelines for GYN-SABR treatment.

Is there a role for a brachytherapy vaginal cuff boost in the adjuvant management of patients with uterine-confined endometrial cancer?

PURPOSE/OBJECTIVE: Many patients who have uterine-confined endometrial cancer with prognostic factors predictive of recurrence are treated with adjuvant pelvic radiation. The addition of a brachytherapy vaginal cuff boost is controversial. MATERIALS AND METHODS: Between 1983 and 1993, 270 patients received adjuvant postoperative pelvic irradiation following hysterectomy for Stage I or II endometrial cancer. Group A includes 173 patients who received external beam irradiation alone (EBRT), while group B includes 97 patients who received EBRT with a vaginal brachytherapy application. The median dose of EBRT was 45 Gy. Vaginal brachytherapy consisted of a low dose rate ovoid or cylinder in 41 patients, a high dose rate cylinder in 54 patients, and a radioactive gold seed implant in two patients. The median follow-up time was 64 months. The two groups were compared in terms of age, histologic grade, favorable versus unfavorable histology, capillary space invasion, depth of myometrial invasion, and pathologic stage. RESULTS: Chi-square analysis revealed that the only difference between the two groups was the presence of more Stage II patients in group B (38% versus 14%). No difference was detected for 5 year pelvic control and disease-free survival rates between groups A and B. CONCLUSION: There is no suggestion that the addition of a vaginal cuff brachytherapy boost to pelvic radiation is beneficial for pelvic control or disease-free survival for patients with Stage I or II endometrial cancer. Prospective randomized trials designed to study external irradiation alone versus external beam treatment plus vaginal brachytherapy are unlikely to show a positive result. Because EBRT provides excellent pelvic control, protocol development for uterine-confined corpus cancer should focus on identifying patients at risk for recurrence as well as other means of augmenting EBRT (e.g. addition of chemotherapy) in order to improve disease free survival in those subgroups.

Which prognostic factors influence the outcome of patients with surgically staged endometrial cancer treated with adjuvant radiation?

PURPOSE: Despite the fact that retrospective reviews have documented pelvic failure rates ranging from 15-20% in patients with high-risk uterine-confined endometrial cancer who have received no or "inadequate" RT, the role of RT has been questioned. We sought to analyze pelvic control and disease-free survival for a large data base of women with corpus cancers managed with initial surgery followed by adjuvant irradiation. METHODS AND MATERIALS: Between 1983 and 1993, 294 patients received adjuvant postoperative RT from one of three academic radiation practices. RT consisted of vaginal brachytherapy alone in 28 patients, pelvic RT in 173 patients, pelvic RT with vaginal brachytherapy in 97 patients, and whole abdominal RT in 2 patients. Lymph nodes were evaluated in 49%. The median number of pelvic and periaortic LN in the pathology specimen were 6 and 4, respectively. Median follow up was 63 months. RESULTS: 5-year disease-free survival (DFS) rate and pelvic control rates were 86 and 95%, respectively. Patient-related, treatment-related, and tumor-related characteristics were assessed for the effect on time to relapse. Unfavorable histology, older age, and capillary space invasion were univariately associated with decreased DFS and pelvic control. Pathologic Stage II patients had significantly worse DFS than Stage I patients. Multivariate analysis revealed that age, capillary space invasion, and histology were jointly predictive of disease free survival. CONCLUSION: The excellent pelvic control and disease-free survival of patients with uterine-confined disease in this series suggest that adjuvant RT should continue for patients with high risk disease. This analysis of a large group of postoperatively treated patients will provide a basis for determining alternative treatment strategies for patients who have an increased risk of disease recurrence despite RT.

The relationship of local and distant failure from endometrial cancer: defining a clinical paradigm.

PURPOSE: Recently, statistical methods have been developed to rigorously assess the relationship between local and distant failures. Such methodology has successfully been applied to a variety of tumors including those arising in the prostate, breast, and cervix. To date, no published data are available to generate a hypothesis to characterize the relationship between local and distant failure for endometrial cancer. The present analysis was undertaken to determine the effect of locoregional control on subsequent metastatic dissemination among women with pathologically staged endometrial cancer treated by hysterectomy followed by adjuvant radiotherapy. METHODS: The series consisted of 394 patients with FIGO stages I-III endometrial cancer who were surgically staged prior to irradiation [median external beam dose 45 Gy +/- brachytherapy (median vaginal surface dose, 30 Gy)]. The duration of follow-up ranged from 2 to 151 months, with a median of 62 months. Multiple factors were evaluated to determine the associations with distant relapse including FIGO pathological stage, grade, histopathologic subtype (adeno vs papillary/papillary-serous/clear cell), depth of myometrial penetration, age, and local disease status. Time-dependent survival models were generated to assess the influence of local failure on distant metastases. RESULTS: For the entire series, the 5-year actuarial rates of local and distant failures were 9 and 20%, respectively. Women who failed locally had nearly a fourfold risk of failing distantly compared to those who remained locally controlled (P = 0.02). Moreover, the earlier a local failure developed (e.g., within 1 year vs within 3 years), the more likely it was to be associated with distant metastases (P < 0. 05). The univariate correlations of other factors with the 5-year rate of freedom from distant relapse also disclosed significant associations for grade, histology (adenoca vs papillary/papillary-serous/clear cell), and FIGO path stage. In multivariate analysis, only local control, low grade (grade 1 and 2), and early pathological stage were independently related to the likelihood of achieving freedom from distant relapse. CONCLUSIONS: Distant dissemination of endometrial cancer may develop secondary to local failure. Optimization of local control is therefore necessary if long-term cure is to be achieved. The limits of the current database cannot establish whether local failure is a cause of distant spread or a high-risk marker for metastases; however, ongoing national cooperative trials may resolve this controversy.

Efficacy of a belly board device with CT-simulation in reducing small bowel volume within pelvic irradiation fields.

PURPOSE/OBJECTIVE: Acute and chronic small bowel toxicity associated with pelvic irradiation limits dose escalation for both chemotherapy and radiotherapy for rectal cancer. Various surgical and technical maneuvers including compression and belly board devices (BBD) have been used to reduce small bowel volume in treatment fields. However, quantitative dose volume advantages of such methods have not been reported. In this study, the efficacy of BBD with CT-simulation is presented with dose-volume histogram (DVH) analyses for rectal cancer. METHODS AND MATERIALS: Twelve consecutive patients referred to our department with rectal cancer were included in this study. Patients were given oral contrast 1.5 h prior to scanning and instructed not to empty their bladder during the procedure. The initial CT scan without BBD was taken in the prone position with an immobilization cast. A second CT study was performed with a commercially available BBD consisting of an 18-cm thick hard sponge with an adjustable opening (maximum 42 x 42 cm2). All patients were positioned prone over the BBD so that the opening was above the treatment volume and usually extended from the diaphragm to the bottom of the fourth lumbar spine. Image fusion between both sets of CT scans (with and without BBD) was performed using common bony landmarks to maintain the same target volume. The critical structures including small bowel and bladder were delineated on each slice for DVH analysis. On each study, a three-field optimized plan with conformal blocks in beams-eye-view was generated for volumetric analysis. The DVHs with and without BBD were evaluated for each patient. RESULTS: The median age and body weight of 12 patients (4 females and 8 males) were 57.5 years and 82.7 kg, respectively. The changes in posterior-anterior (PA) and lateral separation with and without BBD at central axis slices were analyzed. The changes in lateral separation were minimal (<0.8 cm); however, the PA separation was reduced by 11.3 +/- 3.3% when BBD was used. The reduction in PA separation was directly related to the reduction in small bowel volume. The small bowel volume was significantly reduced with a median reduction of 70% (range 10-100%) compared to the small bowel volume without BBD. The small bowel volume reduction did not correlate either with body weight, age, gender, or sequence of radiation treatment with surgery (pre-op vs. post-op). The DVH analysis of small bowel with BBD showed significant volume reduction at each dose level. For 50% patients, the DVH analysis demonstrated an increase in bladder volume with BBD. All patients treated with the BBD completed their treatment without any break and without significant acute gastrointestinal or genitourinary toxicity. CONCLUSIONS: For rectal cancers, small bowel is the dose-limiting structure for acute and chronic toxicity. The use of the BBD should improve the tolerance of aggressive combined modality treatment by reducing the small bowel volume within the pelvis compared to the prone position alone. The BBD provides an easy, economical, comfortable, and noninvasive technique to displace small bowel from pelvic treatment fields. The small bowel volume is dramatically reduced at each dose level. The volume reduction does not correlate with gender, age, weight, pelvic separation, and sequence of radiation treatment vs. surgery.

Intra- and perioperative complications associated with tandem and colpostat application for cervix cancer.

PURPOSE: The purpose of this study was to chronicle the acute morbidity associated with the implantation of tandems and colpostats in women with carcinoma of the cervix; to determine factors that predispose to the development of such complications; and to assess whether the use of ultrasound allowed the apparatus to be safely implanted in women at relatively high risk for perforation of hollow viscous organs. METHODS: A database from two Philadelphia institutions was used to assess the aforementioned factors among 143 tandems/colpostats inserted into 100 women with cervix cancer. Twenty patients had insertion under ultrasound guidance because of stenotic cervical os, fibrosis from external-beam irradiation, indeterminate orientation of endometrial cavity axis, or previous perforation. Univariate and multivariate analyses were performed to identify predictors of intra- and perioperative complications. RESULTS: Intraoperative complications occurred in 7 of 143 placements (5%). These included uterine perforations (n = 4), vaginal lacerations (n = 2), and one instance of bladder perforation. Only older age, whether entered as a continuous or a dichotomous variable, was associated statistically with these complications. Perioperative complications (e.g., fever, bowel obstruction, exacerbation of chronic obstructive pulmonary disease, cardiac complication) occurred in 54 of 143 implanted women. In univariate analysis, older age and underlying chronic obstructive pulmonary disease (COPD) appeared to be associated with perioperative complications. A multivariate analysis showed that underlying COPD predisposed to perioperative complications during the first implant and that age over 60 years independently predicted for complications during any implant. CONCLUSIONS: Intraoperative complications are relatively rare events. Ultrasonography seems to allow safe intrauterine insertion of the tandem despite the selection of difficult cases for this adjunctive imaging tool. Patient age over 60 years independently predicts for perioperative complications. COPD predicts for perioperative complications during the first but not the second implant, implying that physicians are able to optimize the medical management of pulmonary disease to allow a second implant to be performed more safely.

Improved outcome in patients treated with postoperative radiation therapy for pathologic stage I/II endometrial cancer.

PURPOSE: To evaluate prognostic factors and treatment outcome for high risk pathological Stage I and II endometrial cancer patients treated with consistent postoperative radiation therapy (RT) in a single institution and to compare these results to series where RT was variably applied. METHODS AND MATERIAL: Between 1986 and 1993, 98 pathologic Stage I and II endometrial cancer patients received postoperative RT at the Fox Chase Cancer Center. Papillary serous and clear cell histologies were excluded. Fifty-five patients underwent lymph node evaluation. In 17 patients, RT consisted of intracavitary brachytherapy alone to a median dose of 21 Gy, and in 81 patients, RT consisted of external beam RT to a median dose of 45 Gy followed by intracavitary brachytherapy to a median dose of 12 Gy. Intracavitary brachytherapy generally consisted of three high dose rate implants with the dose prescribed to a depth of 0.5 cm. Median follow up was 47 months. RESULTS: The 5-year overall survival (OS), disease free survival (DFS), and freedom from pelvic recurrence (FPR) rates were 83, 85, and 89%, respectively. Pelvic recurrence either as the sole pattern of failure or combined with distant metastases was seen in 2 and 7% of patients, respectively. Distant metastases alone occurred in 4% of the patients. Univariate analysis of prognostic factors including age, grade, capillary lymphatic space invasion, depth of myometrial invasion, type of lymph node evaluation, pathologic stage, the use of brachytherapy and the number of risk factors was performed for OS, DFS, FPR, and FDM. Capillary lymphatic space invasion was the only statistically significant predictor for reduced DFS. Absence of lymph node dissection as well as a higher number of risk factors showed a trend toward poorer DFS (p = 0.06 for both). Multivariate analysis revealed older age to be the only factor significant for reduced DFS, with the presence of capillary lymphatic space invasion and the absence of a lymph node dissection showing a trend toward poorer outcome (p = 0.07). CONCLUSIONS: The results of this study suggest a continued role for the use of postoperative RT in the treatment of patients with high risk endometrial cancer and will be compared to other series with similar high-risk factors.

Wound complications after resection and immediate postoperative brachytherapy in the management of soft-tissue sarcomas.

BACKGROUND: When used as the sole source of postoperative radiotherapy, brachyradiation therapy (BRT) (4,500-6,000 cGy) should be delayed beyond the fourth postoperative day to minimize wound complications. However, when 1,000-2,000 cGy BRT are given as a "boost" to the tumor bed, it is unclear if a similar treatment delay is necessary. The purpose of this review was to determine the incidence of wound complications when BRT (1,000-2,000 cGy) is administered < or = 48 h after soft-tissue resection. METHODS: The results of treatment in 21 patients with soft-tissue sarcomas of the extremity and superficial trunk treated with resection, immediate postoperative brachytherapy, and external beam radiation were reviewed. All patients were followed through the completion of radiation (median follow-up 30 months). A median of seven (range 3-24) after-loading catheters were placed at the time of resection and were loaded with iridium-192 a median of 2 days postoperative to deliver 1,000-2,000 cGy radiation. RESULTS: Eight patients (38%) experienced minor wound complications (seromas, wound separation, and flap edge necrosis) within 30 days of operation. There were no early complications that required reoperation or delayed further therapy. CONCLUSIONS: Brachytherapy (1,000-2,000 cGy) can be administered < or = 48 h postoperatively with a low risk of major wound complications. Minor wound complications are common but do not delay further treatment.

Bony landmarks are not an adequate substitute for lymphangiography in defining pelvic lymph node location for the treatment of cervical cancer with radiotherapy.

PURPOSE: Curative radiotherapy (RT) for carcinoma of the cervix requires adequate irradiation of regional lymph node groups. The best nonsurgical method of defining lymph node anatomy in the pelvis remains the lymphangiogram (LAG). This study was designed to determine if bony landmarks could accurately substitute for LAG as a means of determining lymph node position for the purpose of pelvic RT treatment planning. METHODS AND MATERIALS: The post-LAG simulation films of 22 patients treated at the Fox Chase Cancer Center for cervical cancer were examined. On anterior/posterior (A/P) simulation films, the distance of lymph nodes was determined from the top, middle, and bottom of the sacroiliac joint, and at the pelvic rim, 1 and 2 cm above the acetabulum. On lateral (LAT) simulation films, lymph node position was measured at points 0, 4, and 8 cm along a line from the bottom of L5 to the anterior aspect of the pubic symphysis. Positive values represent lateral and anterior distances relative to the reference point on A/P and LAT films, respectively. Negative values represent distances in the opposite direction. The adequacy of standard pelvic fields as defined by the Gynecologic Oncology Group (GOG) (A/P: 1.5 cm margin on the pelvic rim; LAT field edge is a vertical line anterior to the pubic symphysis) was also examined. Data are expressed as the mean +/- two standard deviations, (i.e. 95% confidence level). RESULTS: On A/P simulation films, the distance of visualized lymph nodes had mean values of -1.6 +/- 1.7 cm (range -4.1 to -0.4 cm), -1.3 +/- 1.5 cm (range -3.4 to 0.0 cm), and 1.2 +/- 1.8 cm (range -1.0 to 2.6 cm) from the sacro-iliac (SI) joint at the superior, middle, and inferior points, respectively. The mean distance of the nodes from the pelvic rim at points 1 and 2 cm above the acetabulum was 0.3 +/- 1.2 cm (range -0.6 to 1.8 cm) and 0.2 +/- 1.8 cm (range -1.6 to 2.1 cm), respectively. On LAT simulation films, the distance of lymph nodes from points 0, 4, and 8 cm from the previously described reference line had mean values of 2.0 +/- 1.0 cm (range 1.3 to 3.0 cm), 0.9 +/- 3.9 cm (range -1.9 to 5.1 cm), and 1.8 +/- 2.1 cm (range -0.8 to 3.5 cm), respectively. Ten of 22 (45%) patients would have had inadequate nodal irradiation if their fields had been designed according to standard GOG parameters. In all cases, these incompletely irradiated lymph nodes were from the lowest of the lateral external iliac group. CONCLUSION: Great variability in pelvic lymph node location is demonstrated when LAG is used to directly visualize their location. Bony structures are inaccurate landmarks for pelvic lymph node position. The GOG standard pelvic fields are not consistently adequate to cover all lateral external iliac lymph nodes, although the clinical significance of this subgroup of lymph nodes is not known. At this time, LAG remains the ideal radiographic modality to define anatomic location of regional lymph nodes for pelvic RT treatment planning. The clinical importance of the most lateral group of external iliac lymph nodes in various stages of cervical cancer represents a potential area of future research.

The efficacy of cranial irradiation in ovarian cancer metastatic to the brain: analysis of 32 cases.

OBJECTIVE: To determine the role of irradiation in the management of brain metastases from epithelial ovarian cancer. METHODS: Tumor registries from five university cancer centers were searched to identify ovarian cancer patients with brain metastases. During a 30-year period (1965-1994), 4027 ovarian cancer patients were evaluated, 32 of whom were found to have cerebral metastases. Each received fractionated whole-brain irradiation (median dose 30 Gy, range 20-52.5). Five patients received concomitant chemotherapy with whole-brain irradiation. RESULTS: The median survival time for the whole population was 4 months. For the entire series, symptomatic response (complete response and partial response) was achieved in 23, 16 of whom were palliated until death. Patients with higher Karnofsky performance status (70 or above versus below 70) were more likely to derive a palliative response and attained a statistically significant survival advantage. No other factor predicted the likelihood of deriving a palliative response or a survival advantage after treatment. CONCLUSIONS: In this large review of patients with cerebral metastases from ovarian cancer, we found that most of those treated with whole-brain irradiation achieved palliation until death. Nearly all women with high performance status derived durable palliation from cerebral irradiation. Whole-brain irradiation was an effective means of palliating ovarian cancer metastatic to the brain and provided a favorable alternative to other means of management.

Postoperative radiation therapy for surgically staged endometrial cancer: impact of time factors (overall treatment time and surgery-to-radiation interval) on outcome.

PURPOSE: To evaluate the impact of prolonged overall radiation treatment (RT) time and surgery-to-radiation interval on local control (LC) and disease-specific survival (DSS) of surgically staged endometrial cancer patients in relation to known prognostic factors. METHODS AND MATERIALS: Between 1971 and 1993, 195 endometrial cancer patients received postoperative RT at the Fox Chase Cancer Center. All patients underwent total abdominal hysterectomy (TAH), with 38% also having lymph node sampling. All patients received whole pelvic external beam RT to a median dose of 45 Gy (range 40 to 60 Gy). Sixty-nine percent received a vaginal cuff boost with either low dose rate or high dose rate brachytherapy. Tumor and treatment factors were analyzed for impact on LC and DSS. Median follow-up was 47 months (range: 6 to 187 months). RESULTS: The overall actuarial 5-year LC rate was 85%. In multivariate analysis, tumor grade, pathologic stage, external radiation dose, and surgical lymph node evaluation were independent prognostic variables for improved LC. Surgery-to-radiation interval of greater than 6 weeks was a marginally significant factor for decreased LC (p = 0.06). Overall RT time and external beam treatment time did not appear to impact LC rates. The overall actuarial 5-year DSS rate was 86%. In multivariate analysis, depth of myometrial invasion, tumor grade, and pathologic stage were independent prognostic variables for DSS. In addition, a surgery-to-radiation interval of greater than 6 weeks was significantly associated with decreased DSS (p < 0.005). CONCLUSIONS: Surgery-to-radiation interval of greater than 6 weeks is a significant independent prognostic variable for decreased DSS and a marginally significant variable for decreased LC in patients irradiated postoperatively for endometrial cancer. Other time factors (overall RT time and external beam treatment time) did not appear to impact outcome. Based on this analysis, postoperative radiation therapy for endometrial cancer should be initiated within 6 weeks following surgery.

Polarographic needle electrode measurements of oxygen in rat prostate carcinomas: accuracy and reproducibility.

PURPOSE: The oxygenation status of tumors may be important for predicting tumor response to therapy. Previous studies with the anaplastic (R3327-AT) and well-differentiated (R3327-H) Dunning rat prostate tumors using indirect assays of tumor oxygenation indicated the relative hypoxic and radioresistant nature of the anaplastic tumor. We now report direct measurements of oxygen in these tumors made with the pO2 histograph to determine: (a) whether a significant difference in oxygenation status could be detected between them: (b) whether sequential measurements on the same tumor gave similar values; and (c) whether tumor oxygenation correlated with tumor volume. METHODS AND MATERIALS: R3327-AT and R3327-H tumors were grown in Fischer X Copenhagen rat to volumes of 1.0-7.0 cm3. Electrode measurements (100-200) were made in tumors in anesthetized animals along two parallel tracks. Repeat measurements were made at 1-5 days along different parallel tracks. Oxygen partial pressures of muscle tissue were measured and served as a normal tissue control. Statistical analyses were applied to determine whether tumor oxygen levels were different between the two tumor histologies, whether sequential measurements in the same tumor were reproducible, and whether tumor oxygenation correlated with tumor volume. RESULTS: The average median pO2 of the well-differentiated (n = 15) and the anaplastic (n = 15) tumors was 6.0 mmHg (SE +/- 1.3) and 2.2 mmHg (SE +/- 0.3), respectively. The average median pO2 of normal rat muscle (n = 15) was 23.6 mmHg (SE +/- 2.0). These values represent highly significant differences in oxygen concentration between the two tumors and rat muscle. The differences in average mean pO2 values were also highly significant. Repeat measurements in the same tumors on different days gave average median values of 4.7 and 2.2 mmHg in the R3327-H (n = 15) and R3327-AT (n = 15) tumors, respectively. For these repeat measurements, median pO2 values decreased in 15 and increased in 15 tumors, and were not significantly different from the first measurements. The average differences observed in median pO2 were 37% (SE +/- 7) and 58% (SE +/- 10) for the R3327-H and R3327-AT tumors, respectively. No significant correlation was observed between pO2 levels and the tumor volumes investigated in this study. CONCLUSIONS: The median pO2 values of the anaplastic Dunning tumors were significantly lower than those of the well-differentiated tumors (p < 0.001). Oxygen levels in both tumors were significantly lower than those measured in normal rat muscle (p < 0.00005). Repeat measurements of median pO2 in the same tumors were not significantly different for either tumor model (p > 0.5). The changes observed in pO2 distributions within individual tumors from day to day may indicate true dynamics of its oxygenation status and/or the limits of electrode measurements, by sampling along only two insertion sites. The electrode measurements of pO2 in these tumor models are reproducible and confirm previously detected oxygenation differences between the anaplastic and well-differentiated tumors.

Management of extremity soft tissue sarcomas with limb-sparing surgery and postoperative irradiation: do total dose, overall treatment time, and the surgery-radiotherapy interval impact on local control?

PURPOSE: To evaluate potential prognostic factors in the treatment of extremity soft tissue sarcomas that may influence local control, distant metastases, and overall survival. METHODS AND MATERIALS: Sixty-seven patients with extremity soft tissue sarcomas were treated with curative intent by limb-sparing surgery and postoperative radiation therapy at the Fox Chase Cancer Center or the Hospital of the University of Pennsylvania, between October 1970 and March 1991. Follow-up ranged from 4-218 months. The median external beam dose was 60.4 Gy. In 13 patients, interstitial brachytherapy was used as a component of treatment. RESULTS: The 5-year local control rate for all patients was 87%. The 5-year local control rate for patients who received < or = 62.5 Gy was 78% compared to 95% for patients who received > 62.5 Gy had larger tumors (p = 0.008) and a higher percentage of Grade 3 tumors and positive margins than patients who received < or = 62.5 Gy. The 5-year local control rate for patients with negative or close margins was 100% vs. 56% in patients with positive margins (p = 0.002). Cox proportional hazards regression analysis was performed using the following variables as covariates: tumor dose, overall treatment time, interval from surgery to initiation of radiation therapy, margin status, grade, and tumor size. Total dose (p = 0.04) and margin status (p = 0.02) were found to significantly influence local control. Only tumor size significantly influenced distant metastasis (p = 0.01) or survival (p = 0.03). CONCLUSION: Postoperative radiation therapy doses > 62.5 Gy were noted to significantly improve local control in patients with extremity soft tissue sarcomas. This is the first analysis in the literature to demonstrate the independent influence of total dose on local control of extremity soft tissue sarcomas treated with adjuvant postoperative irradiation.

Treatment-related myelodysplastic syndrome following abdominopelvic radiotherapy for endometrial cancer.

A patient with grade II endometrial adenocarcinoma underwent TAH/BSO. The tumor penetrated 50% of the myometrium. A lesion from the serosa of the sigmoid colon was removed and contained metastatic adenocarcinoma. Metastatic tumor was also found in the common iliac lymph nodes. Postoperatively the patient was treated with abdominopelvic radiotherapy to 30 Gy. The pelvis was boosted to a dose of 46.2 Gy. The vaginal apex was then treated with three applications of high-dose-rate brachytherapy to a total dose of 12 Gy. The patient was doing well with no evidence of recurrence 52 months following treatment when she was diagnosed with a myelodysplastic syndrome. Cytogenetic analysis revealed aberrations of chromosomes 5 and 7, which is highly suggestive of a treatment-related process. Myelodysplasia induced by radiotherapy alone is an unusual but recognized event.

Improved treatment planning for the Syed-Neblett template using endorectal-coil magnetic resonance and intraoperative (laparotomy/laparoscopy) guidance: a new integrated technique for hysterectomized women with vaginal tumors.

The Syed template (Alpha-Omega Services, Bellflower, CA) represents an advance in interstitial gynecologic brachytherapy; however, its appeal is diminished by inaccuracies in target definition secondary to suboptimal imaging of gynecologic tumors and the risk of viscus perforation during a "blind" procedure. Magnetic resonance (MR) scanning with an endorectal coil and computed tomography were studied as a possible tool to improve target definition and maximize treatment planning with Syed templates. Abdominopelvic contents could be visualized directly through a laparotomy incision or indirectly with a laparoscopic video display to allow further target definition and minimize complications associated with blind procedures after hysterectomy. The synthesis of these techniques with Syed template applications was attempted to potentiate the utility of this brachytherapy system. Five patients with apical vaginal tumors which arose after previous hysterectomies (two endometrial cancer recurrences, one recurrent uterine sarcoma, two primary vaginal cancers) were referred for radiotherapy. In three cases, external beam pelvic radiotherapy (median dose, 45 Gy; range, 45-50.4 Gy) was delivered initially. In all cases, the Syed applicator was used for the brachytherapy component of the treatment. In two cases, high-resolution MR images (400 x 400 microns) of the vaginal apex were obtained after insertion of an endorectal surface coil. The images defined the relationships between the template, target volume, bladder, rectum, and intestine. The other three cases were planned with computerized tomography (CT). In all cases, intraoperative examination of the abdominopelvic contents was provided when laparotomy and/or laparoscopy was performed by the surgical team. The median brachytherapy dose prescribed to the isodose envelope covering the target volume was 40 Gy (range, 31-50 Gy). In all cases, the target volumes could be encompassed by the 60 cGy/hr isodose line. Tumor volume estimation was better with MR than CT. Procedure time was shorter with laparoscopy than with laparotomy. In two cases, bowel displacement was performed (one tissue expander, one omental sling) to prevent viscus perforation by interstitial needles. Four of five patients responded completely to the treatment. In three cases, local control was maintained at a median follow-up of 11 months. In conclusion, endorectal coil MRI may be advantageous to CT of the pelvis in that it allows preplanning to be achieved with greater precision and with less planning time. Major intraoperative complications (i.e., perforation of hollow viscus organs) can be avoided when the course of interstitial catheters is visualized from above by the surgical team.(ABSTRACT TRUNCATED AT 400 WORDS)

The management of early ovarian cancer.

Approximately one third of patients with epithelial ovarian cancer present with localized or early-stage disease. Prognostic features identify certain subsets of patients with good risk characteristics who do not require adjuvant treatment after comprehensive surgical staging and cytoreduction. Only a minority of patients undergo such a complete procedure, which often results in understaging of these patients. In the United States, patients with poor prognostic features, such as stage IC to II disease, poorly differentiated histologic grade, clear cell histology, dense adhesions, and large volume ascites, have received adjuvant chemotherapy. Single-agent or combination chemotherapy, whole abdominal irradiation, and intraperitoneal phosphorus 32 have been evaluated, although no modality has been shown to improve overall survival. Randomized trials investigating the optimal therapy or whether any therapy is truly effective are in progress. Until the completion of these trials, the most common postoperative adjuvant therapy in these patients in this country remains combination chemotherapy.

Management of retroperitoneal sarcomas: does dose escalation impact on locoregional control?

PURPOSE: Only 50% of patients with retroperitoneal sarcomas undergo complete resection and of these, 47% develop local tumor recurrence. To determine whether irradiation with dose escalation improves locoregional control, we reviewed the experience with adjuvant radiotherapy in the treatment of retroperitoneal sarcomas at the Fox Chase Cancer Center and the Hospital of the University of Pennsylvania. METHODS AND MATERIALS: Twenty-one patients with retroperitoneal sarcomas were treated with curative intent with surgical resection and radiation therapy at Fox Chase Cancer Center or the Hospital of the University of Pennsylvania between May 1965 and July 1992. Follow-up ranged from 14-340 months. Nineteen patients were treated postoperatively and 2 preoperatively. Radiation doses were between 36.0 Gy and 90.0 Gy (median 54.0 Gy). RESULTS: The 2-year rates of local control and survival were 72% and 69%, respectively. Tumor size, stage, grade, and histology did not influence local control. Two of eight patients (25%) who received a total dose of > 55.2 Gy experienced local failure compared to 5 of 13 (38%) who received < or = 55.2 Gy. One patient experienced a small bowel obstruction that required surgical intervention. There were no other severe complications. CONCLUSION: Postoperative treatment with radiotherapy using a dose > 55.0 Gy is recommended for patients with retroperitoneal sarcomas following surgical resection due to the significant likelihood of local recurrence. Innovative adjuvant radiation techniques to escalate doses to greater than 55.0 Gy including intraoperative radiation therapy, brachytherapy, or use of small bowel exclusion devices to reduce small bowel toxicity should be considered for retroperitoneal sarcomas.

Recurrent ovarian cancer. Effective radiotherapeutic palliation after chemotherapy failure.

BACKGROUND: Recurrent ovarian cancer after frontline chemotherapy is incurable; however, palliation of focal lesions often is needed to alleviate symptoms. Because published response rates to palliative irradiation (RT) among patients failing cisplatin-based chemotherapy are scarce, the authors attempted to define the palliative role of radiotherapy for symptomatic, localized ovarian cancer recurrences. Factors predicting a response to RT also were sought. METHODS: Between 1987 and 1993, 33 patients with ovarian cancer were irradiated at 47 sites with palliative intent after failing cisplatin-based chemotherapy regimens. Sites irradiated included the pelvis (n = 33), abdomen (n = 5), chest (n = 4), brain (n = 3), and other (n = 2). Median RT dose was 35 Gy (range: 7.5-45 Gy). The median fraction size was 2.5 Gy (range, 1-5 Gy). To determine dose effectiveness, the biologic effective dose (BED) was calculated according to the following formula: BED = total dose (1 + fractional dose/alpha/beta) using an alpha/beta value of 10. The median BED10 was 44 (range, 9-72). RESULTS: For the entire group, complete palliative response was 51% and overall palliative response was 79%. The median duration of palliation was 4 months, which reflected palliation until death in 90% of cases. The overall response rates by symptoms were: pulmonary symptom relief in 75%, vaginal bleeding control in 90%, rectal bleeding control in 85%, pain relief in 83%, and neurologic symptoms controlled in 50%. The likelihood of obtaining complete symptomatic response was significantly increased among those with high Karnofsky performance status (KPS > or = 70 vs. KPS < 70; 69% vs. 36%, P < 0.03) and among those who received a higher biologically effective dose of irradiation (BED10 > or = 44 vs. BED10 < 44; 68% vs 35%, P < 0.03). Complete palliative response rates were not influenced by histologic differentiation, the number of previously administered cisplatin regimens, or patient age. Treatment-related acute morbidities included diarrhea in 5 of 38 (13%) patients treated through abdominal or pelvic fields, and esophagitis in 2 of 5 treated through thoracic portals. Only one severe late morbidity (small bowel obstruction) was observed. CONCLUSIONS: Durable palliation of patients with ovarian cancer that recurs after cisplatin-based chemotherapy can be achieved with local radiotherapy, especially among patients with high performance status. Biologically effective doses of at least 44 Gy10 (e.g., 3500 cGy/14 fractions = BED10 of 44) should be sought to maximize the probability of complete response. Such dose-fractionation schedules can be delivered expeditiously with acceptable tolerance. These results are comparable to the published experience of second-line chemotherapy in the treatment of focally symptomatic ovarian cancer recurrences.