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.

The effect of whole-brain radiation (WBI) and Karnofsky performance status (KPS) on survival of patients receiving stereotactic radiosurgery (SRS) for second brain metastatic event.

OBJECTIVE: The objective of the present study is to analyze prognostic factors affecting survival of patients receiving stereotactic radiosurgery (SRS) for second brain metastatic event (SBME) following initial treatment with whole brain irradiation (WBI), surgical resection, or previous SRS. METHODS: The 88 patients treated with SRS for SBME at Philadelphia CyberKnife between January 2006 and October 2013 were included in the study group. Cox proportional-hazards regression was used to identify prognostic factors that significantly impacted survival from the time of SRS for SBME. Independent variables considered in survival analysis included primary disease, first brain metastatic event (FBME) treatment type, age, gender, number of brain metastases at SBME, Karnofsky performance status (KPS), recursive partitioning analysis (RPA), and presence of extracranial metastasis. RESULTS: The median survival for all patients was 7.31 months. Log-rank comparison of Kaplan-Meier survival curves revealed significant impact by Karnofsky performance status (p = 0.003), RPA class (p = 0.008), age (p = 0.014), and FBME treatment type (p = 0.010). Median survival was longer for patients who had not previously received WBI (14.7 months). Median survival was further increased in patients who had not received previous WBI and demonstrated KPS scores of 70-100 (19.5 months). Patients who received WBI prior to SBME treatment experienced a pronounced decrement in median survival (5.7 months), yet patients in this group who demonstrated strong KPS scores (80-100) experienced significantly increased survival (15.5 months). CONCLUSIONS: The outcomes of SRS for SBME are most favorable for patients who have not received previous WBI or who have maintained higher performance status despite previous WBI.

Impact of improved irradiation technique, age, and lymph node sampling on the severe complication rate of surgically staged endometrial cancer patients: a multivariate analysis.

PURPOSE: Limited information is available regarding factors that predispose to complications following postoperative pelvic radiotherapy (RT) for endometrial cancer. To address this issue, patients with clinically staged I/II endometrial cancer who received postoperative RT following total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH/BSO) with or without lymph node sampling (LNS) were studied. PATIENTS AND METHODS: From 1960 through 1990, 235 patients with adenocarcinoma of the endometrium received postoperative RT after surgical staging. Multiple factors were evaluated to determine associations with severe complications. Pretreatment factors included age, stage, comorbidities. Treatment-related factors consisted of LNS, total RT dose, volume of RT fields, dose per fraction, total number of RT fields, number of RT fields treated per day, machine energy, and addition of vaginal implant. RESULTS: The 5-year actuarial risk of a severe complication was 5.5%. Factors associated with an increased risk of complications in univariate analysis included age more than 65 years (11% v 2%), use of only one portal per day (40% v 3%), use of anteroposterior/posteroanterior fields (23% v 4%), total dose > or = 50 Gy (8% v 2%), and LNS (11% v 3%). In a multivariate analysis, only older age, LNS, and the use of one field per day were significant. Increased risks associated with a total dose > or 50 Gy and the anteroposterior/posteroanterior technique were entirely attributable to the use of one field per day. A subanalysis among patients who had adequate RT techniques (eg, multiple fields treated per day) showed a significant increase in complications (7% v 1%) for those with and without LNS, respectively. CONCLUSIONS: Severe complications associated with adjuvant RT for endometrial cancer were increased among patients who were older or underwent LNS or received suboptimal RT technique. Pelvic RT using proper methods can be delivered with acceptable risks.

Radiotherapy for the treatment of locally recurrent cervical cancer.

Following radical hysterectomy for stage I-IIA cervical carcinoma, 10%-15% of women will have a recurrence. Sixty percent of these recurrences will be located in the pelvis alone. The treatment of a localized pelvic recurrence depends on a number of factors, but primarily the history of previous radiation therapy (RT) to the pelvis and the location of the recurrence. For patients without a history of prior treatment, RT with or without chemotherapy can lead to disease-free survival rates of 20%-50% and local control rates of 20%-60%, and should be considered first-line treatment. For those with a history of previous RT and sidewall or nodal recurrences, a combination of surgery and brachytherapy or intraoperative radiotherapy may improve survival for these women who were previously considered incurable. However, this requires special expertise and technology not available at most centers.

Optimizing radiation parameters for cervical cancer.

The treatment of cervical cancer has become increasingly sophisticated with evidence-based guidelines generated from randomized trials directing combined modality programs. The radiotherapeutic guidelines have been derived largely from single institutional experiences coupled with data from the Patterns of Care Studies. The design of external-beam fields has improved because of a better understanding of the anatomy of the cervix, uterus, parametrium, and draining lymph nodes from surgical, lymphangiogram, computed tomography scan, and magnetic resonance imaging series. An improvement in survival and local control with dose intensity (a reduction in overall treatment time and increase in overall dose) has been shown for cervical cancer, especially for locally advanced disease, and these series are highlighted. The use of intracavitary radiation, which is technically accurate, dramatically improves outcome and allows for dose intensity. Alternative brachytherapy techniques, such as high-dose-rate, and interstitial, are discussed. Ways to improve the therapeutic ratio for radiation, including biological factors, are reviewed. More research is necessary to understand the complex dose distribution of external-beam and intracavitary brachytherapy and its relationship to tumor control.

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.

Inaccuracies in using the lumpectomy scar for planning electron boosts in primary breast carcinoma.

PURPOSE: To determine the accuracy of using the lumpectomy scar, specifically the midpoint or center of the scar, to define the tumor bed in the electron beam boost for the treatment of early stage breast carcinoma. METHODS AND MATERIALS: Electron boost simulation films from 316 cases of early breast carcinoma treated with lumpectomy and radiotherapy were reviewed. For each case which had surgically placed lumpectomy bed clips (N = 316), four clinical set-up methods ("hypothetical fields") of several field sizes were compared to the actual location of the tumor bed (as defined by the surgical clips). Each method was based on using the center of the scar as the center of the field and is described as follows: Method 1 uses a standard circular cone of a given diameter, method 2 also uses circular cones, but the diameter is based on the scar length; method 3 uses an oval field in which a constant margin is kept around the scar; method 4 results in an oblong field in which a 2 cm margin is placed on the lateral edge of the scar, but a larger margin around the center of the scar. The adequacy of each of these popular clinical set-up techniques was then analyzed for the population as a whole. "Inadequate" coverage was defined as any portion of the field edge coming within 1 cm of at least one surgical clip. RESULTS: (1) Method 1: Inadequate coverage was found in 43%, 26%, and 17% of cases, using 7, 8, and 9 cm cones, respectively. (2) Method 2: Inadequate coverage was found in 88%, 61%, 36% and 20% of cases, with field size = scar length + 0, 2, 3, and 4 cm, respectively. (3) Method 3: Inadequate coverage was found in 34%, 17%, and 10% of cases, using 3, 3.5, and 4 cm margins, respectively. (4) Method 4: Inadequate coverage was found in 36% and 24% of cases using 3.5 and 4 cm margins around the scar center, respectively. Inadequate coverage was found in 51% and 42% of cases using margins equal to one-half the scar length or one-half the scar length + 1 cm, respectively. CONCLUSION: We conclude that the lumpectomy scar is often a poor indicator of the location of the underlying tumor bed as defined by surgical clips. We recommend the use of clip placement and simulation of the electron boost to maximize target definition.

Pretreatment and treatment factors associated with improved outcome in squamous cell carcinoma of the uterine cervix: a final report of the 1973 and 1978 patterns of care studies.

The Patterns of Care Study (PCS) conducted two national surveys of patients treated in 1973 and 1978 for squamous cell cancer of the uterine cervix. In addition, a survey of patients treated in 1973 from selected large facilities was conducted to establish outcome with "optimal" radiotherapy. The large facility survey consistently reported improved outcome compared to both national average surveys when analyzed by stage and other significant pretreatment factors. That improved outcome was associated with the paracentral (PCS point A) dose and the use of intracavitary irradiation. In this study, we report the pretreatment and treatment factors associated with improved outcome in squamous cell carcinoma of the uterine cervix by analysis of the 1973 and 1978 PCS data. Pretreatment factors associated with improved pelvic control in multivariate analysis include higher Karnofsky Performance Status (KPS) (Stage I and II), older age (Stage I and II), unilateral parametrial involvement (Stage IIB), and unilateral sidewall involvement (Stage III). The only treatment factor associated with improved pelvic control in multivariate analysis is the use of intracavitary irradiation. However, a dose response for infield pelvic control was demonstrated only in Stage III cervix cancer with the highest rate of pelvic control with paracentral (PCS point A) dose greater than 8500 cGy. Multivariate analysis revealed that unilateral parametrial involvement for Stage IIB and unilateral sidewall involvement for Stage III are significant positive prognostic factors with respect to survival after treatment with radiotherapy. No FIGO substage significantly affected survival after radiotherapy. Although FIGO staging is the single most important pretreatment prognostic factor with respect to survival and infield pelvic failure, FIGO substaging deserves reappraisal and further refinement. Major complications were seen in only 9.5% of patients treated with radiotherapy and were stage but not survey related. There is a significant relationship between PCS point A dose and complications with the highest rate of complications for PCS point A dose greater than 8500 cGy. A significant relationship between lateral (external iliac lymph nodes or PCS point P) dose and major complications is also found, and doses greater than 5000 cGy are associated with a significant increase in complications. The PCS has established two sequential national benchmarks of treatment outcome for squamous cell carcinoma of the uterine cervix treated with radiotherapy with respect to survival, infield pelvic control, and complications.(ABSTRACT TRUNCATED AT 400 WORDS)

Tumor and treatment factors improving outcome in stage III-B cervix cancer.

This report reviews 271 patients with Stage III-B squamous cell cancer of the uterine cervix from three national surveys conducted by the Patterns of Care Study. A progressive increase in local control and survival is seen among the three surveys which parallels a progressive increase in paracentral (point A) dose and use of intracavitary treatment. Multivariate analysis reveals extent of pelvic disease (unilateral sidewall vs. bilateral sidewall vs. lower 1/3 vagina) and use of intracavitary treatment to be the only significant tumor and treatment factors associated with local control and survival. With aggressive radiotherapy, local control rates exceeding 65% and survival of 50% at 4 years can be anticipated at the expense of a small increase in complications.

Prognostic value of CA 19-9 levels in patients with carcinoma of the pancreas treated with radiotherapy.

PURPOSE: CA 19-9 has been identified as a tumor marker for pancreatic carcinoma and has been shown to have some utility in predicting outcome in surgically treated patients. The purpose of this study was to evaluate its usefulness as a prognostic indicator in patients treated with radiotherapy. MATERIALS AND METHODS: A retrospective review of all patients treated with radiotherapy of definitive intent (n = 104) for carcinoma of the pancreas at Fox Chase Cancer Center from 1980-1994 was undertaken. Patients were categorized into four groups: Planned preoperative radiation with resection (n = 25); planned preoperative radiation without successful resection (n = 35); postoperative radiation (n = 21); and radiation without planned resection (n = 23). For each group, except those treated without planned resection, median dose for external beam radiotherapy was 50.4 Gy (range = 21.6-63.0 Gy). Those in the remaining fourth group were treated with a median dose of 55.8 Gy (range = 36.0-60.4 Gy). 97% of patients in the first three groups were also treated with 5-FU-based chemotherapy, as were 61% of those in the fourth group. Pretreatment and follow-up CA 19-9 levels were available for 69 patients. RESULTS: Median survival time for all groups was 10 months (range = 1-67 months). Univariate analysis showed significant differences in survival among the groups: Preop with resection 22 months; preop without resection 10 months, postop 17 months; and without planned resection 12 months (p = 0.0005). Overall, patients who underwent resection had a median survival time of 19 months, compared to 11 months in those who did not (p = 0.0006). CA 19-9 level at diagnosis was found to be a significant prognostic indicator on univariate analysis, with a median survival time of 8 months in those having a level greater than the median of 680 U/ml, compared to 20 months in those who did not (p = 0.0003). Similarly, the posttreatment nadir was significant, with a median survival time of 11 months in those with levels above the median of 162.5 U/ml, vs. 26 months in those with levels below 162.5 U/ml (p = 0.001). The median survival time for patients whose CA 19-9 levels decreased in response to treatment by more than 75% was 23 months (range = 6-34 months) vs. 8 months (range = 3-21) in those with 75% or less response (p = 0.003). On stepwise multivariate analysis, pretreatment CA 19-9 level was found to be a significant predictor of survival (p = 0.005). Other potential indicators of outcome, including age, gender, KPS, prediagnosis weight loss, location of tumor, clinical TNM staging, size of lesion, vascular involvement on angiography, and sequence of radiation with respect to resection, were evaluated and were not found to be significant. CONCLUSION: CA 19-9 was demonstrated to be a useful prognostic indicator in patients treated with radiotherapy; other, more traditional, indicators of outcome were of less utility.

The influence of treatment time on outcome for squamous cell cancer of the uterine cervix treated with radiation: a patterns-of-care study.

PURPOSE: To analyze the effect of total treatment time on infield pelvic control and survival for squamous cell carcinoma of the uterine cervix using the combined 1973 and 1978 Patterns of Care (PCS) data base. METHODS AND MATERIALS: Eight hundred thirty-seven evaluable patients were analyzed for the effect of total treatment time on outcome. The Kaplan-Meier method was used to estimate time-to-outcome annual rates. Comparisons of time to failure were performed with the log rank test. Multivariate analysis was performed using the Cox regression analysis. RESULTS: A highly significant decrease in survival (p = .0001) and pelvic control (p = .0001) was demonstrated as the total treatment time was increased from < 6, 6 to 7.9, 8 to 9.9, and 10+ weeks. Stage III accounted for the majority of the adverse effect from the prolongation of total treatment time. Multivariate analysis of total treatment time in addition to previously reported significant pretreatment and treatment factors from the PCS data base revealed three independent factors for infield recurrence, namely Stage I versus II versus III (p = .0001), total treatment time < 6 versus 6 to 7.9 versus 8 to 9.9 versus 10+ weeks (p = .003), and age > 50 versus < or = 50 years (p = .01). When the analysis was performed by stage to evaluate the effect of overall treatment time with respect to the extent of pelvic disease as defined by PCS, total treatment time continued to be an independent prognosticator for infield pelvic control (p = .01) and survival (p = .02) for Stage III but not Stages I and II. CONCLUSION: This study demonstrates a significant adverse effect on survival and pelvic control with prolongation of the total radiation treatment time for Stage III squamous cell cancer of the uterine cervix in multivariate analysis. In the future design of clinical trials, limitations on total treatment time should be rigorously controlled, and the effect of variations in this important factor by altered fractionation schemes should be studied.

Perioperative morbidity of intracavitary gynecologic brachytherapy.

PURPOSE: To define the incidence and severity of perioperative morbidity and its subsequent management with standard tandem and ovoid insertions and to evaluate pretreatment and treatment factors associated with an increased risk of perioperative morbidity. METHODS AND MATERIALS: Ninety-five tandem and ovoid insertions were performed at the Fox Chase Cancer Center between 1985 and 1992 for cervical (n = 91) and endometrial (n = 4) cancer. Patients were placed on antibiotics in 19%, usually for a positive routine preoperative urine culture, but no patient was given prophylactic antibiotic therapy. Deep-vein thrombosis prophylaxis was practiced for 70% of implants and included subcutaneous heparin (40%), graduated compression elastic stockings (16%), and external pneumatic calf compression (14%). All patients were placed on prophylactic diphenoxylate hydrochloride, with doses ranging from three to eight tablets/day. RESULTS: Intraoperative complications were seen in 3% of implants and included two perforations and a vaginal laceration in two patients. Twenty-four percent of implants (16 patients) developed temperatures of > 100.5 (range 100.6 to 103), although only one patient required implant removal because of fever. Management of fever included antibiotics in 35% and acetaminophen only in 65%. Five implants (5%) were removed emergently secondary to presumed sepsis (n = 1), exacerbation of chronic obstructive pulmonary disease, hypotension, change in mental status (n = 3), and myocardial infarction/congestive heart failure (n = 1). No patient developed a deep-vein thrombosis, pulmonary embolism, gastrointestinal obstruction, or died of a postoperative complication. Univariate analysis of pretreatment and treatment factors revealed older age (p < 0.005) and spinal/epidural anesthesia (p < 0.02) to be associated with increased perioperative morbidity, and older age (p < 0.05) and higher ASA classification (p < 0.02) to be associated with severe complications requiring removal of implant. Multivariate analysis revealed only older age (p < 0.01) to be significantly related to perioperative morbidity. CONCLUSIONS: Fever of > 100.5 was seen in 24% of implants and can be managed successfully without removal of the implant in 96% of cases. Use of antibiotics preoperatively and intraoperatively did not reduce the risk of perioperative temperature elevation. Use of routine diphenoxylate hydrochloride prophylaxis was tolerated without ileus or gastrointestinal obstruction clinically. Although routine deep-vein thrombosis prophylaxis is reasonable, our data would support a low risk of deep-vein thrombosis for untreated patients. Severe perioperative morbidity necessitated premature implant removal in only 5% of cases and was related to older age in multivariate analysis.

Analysis of complications in patients with endometrial carcinoma receiving adjuvant irradiation.

We analyzed the complications in 310 patients with pathologically documented endometrial carcinoma who received adjuvant radiation therapy (RT) at Fox Chase Cancer Center between 1970 and 1986. Variables included timing of treatment, technique, total dose, age, diabetes, previous abdominal surgery, hypertension, prior bowel pathology, and lymphadenectomy. According to the FIGO (1985) system, 258 patients had Stage I disease, 48 had Stage II, and one had Stage III. One hundred seventy patients received preoperative (preop) RT, 138 received postoperative (postop) RT, and 2 received preop and postop RT. A 4-field technique was used for 212 of 235 patients receiving external-beam (EX) RT, and 75 patients were treated with intracavitary (IC) RT only. Median follow-up was 5.5 years. Actuarial survival of all 310 patients was 78% at 5 years. Thirty-two complications occurred, involving the rectum, small bowel, femur, or lower extremity. Complications were graded according to the ECOG scoring system as grade 2 (mild) and grades 3, 4, or 5 (serious). One of 75 patients treated with IC RT only experienced a grade-2 complication (proctitis). Of 71 patients receiving 4-field EX RT only, 25 preop (16%) and 14 postop (14%) patients had complications. Of 139 patients treated with both EX and IC RT, grade-2 complications were seen in 5% of 87 preop patients and 12% of 52 postop patients (p = 0.17), whereas serious complications were observed in 4% of each group. Univariate analysis of the variables of interest revealed that the incidence of complications was associated with a lymphadenectomy (p = .03), use of external RT (p less than .01), and decreasing age (p = .04). Multivariate analysis confirmed that use of external RT was the most significant predictor for complications. In conclusion, similar complication rates were found in patients treated with either preop or postop 4-field EX RT. While pelvic RT clearly decreases pelvic relapse in patient with endometrial carcinoma, the risk benefit ratio for treatment of these patients should be carefully considered when recommending adjuvant RT for pelvic control.

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.

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.

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.

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.

Vaginal stenosis and sexual function following intracavitary radiation for the treatment of cervical and endometrial carcinoma.

PURPOSE: This study was designed to document the incidence and degree of vaginal stenosis, sexual activity, and satisfaction in women treated with intracavitary radiation therapy for cervical or endometrial carcinoma. METHODS AND MATERIALS: The incidence of vaginal stenosis in 90 patients treated for either cervical carcinoma (n = 42) or endometrial carcinoma (n = 48) with standard doses of intracavitary radiation from 1989 to 1992 with at least 6 months follow-up was recorded. Vaginal length was measured using a modified vaginal dilator calibrated in centimeters. Semistructured patient interviews documented pretreatment and posttreatment sexual activity and sexual satisfaction. RESULTS: Vaginal length was found to be dependent on diagnosis (cervical vs. endometrial), stage (I vs. II/III), and follow-up interval (6-12 months, 12-24 months, and > 24 months). Slightly more women reported sexual activity post vs. pretreatment (31% active pretreatment vs. 43% active posttreatment). However, 22% of women reported a decrease in sexual frequency and 37% reported a decrease in sexual satisfaction. Reports for all parameters were worse for women treated for cervical carcinoma vs. women treated for endometrial carcinoma with the exception of dyspareunia. CONCLUSION: High-dose radiation for either cervical or endometrial carcinoma at standard doses with or without hysterectomy can cause a decrease in vaginal length as compared to the normal vaginal length of 8 to 9 cm documented by Masters and Johnson. Women treated with intracavitary implants remained as sexually active postimplant as preimplant, however, coital frequency and sexual satisfaction decreased while dyspareunia increased. The decrease in vaginal length may explain in part the decrease in sexual satisfaction but cause and effect have not been established.

Endometrial cancer with para-aortic adenopathy: patterns of failure and opportunities for cure.

PURPOSE: To examine the outcome of patients with advanced endometrial cancer whose para-aortic involvement was diagnosed pathologically or lymphographically. METHODS AND MATERIALS: Fifty patients from four institutions were treated between 1959 and 1990 with preoperative, post-operative, and primary radiotherapy. Para-aortic disease was diagnosed pathologically in 26 patients and lymphographically in the remaining 24 patients. Pathologically diagnosed patients underwent debulking of grossly involved nodes. All patients received external beam treatment through pelvic and para-aortic portals. Median prescribed dose to the pelvic and para-aortic fields was 50 and 47 Gy, respectively. Those treated with primary or pre-operative irradiation also received intrauterine brachytherapy. RESULTS: The actuarial 5-year disease-free survival was 46% for all patients. Para-aortic failure was significantly decreased among patients undergoing lymph node resection (13% versus 39%, respectively). Relapse-free survival and pelvic control tended to improve among patients receiving surgery plus irradiation in comparison to those treated by irradiation alone. Distant metastases were most common among patients with high grade lesions. CONCLUSIONS: Long-term disease-free survival is achievable in endometrial cancer patients with para-aortic lymphadenopathy who are treated with extended-field radiotherapy. Cure is mot attainable among patients with well differentiated, early clinical stage disease who receive combined modality treatment. Survival and local failure are similar for radiologically and pathologically diagnosed patients; however, para-aortic failure as a component of local failure was increased in patients who did not undergo surgical debulking of the adenopathy.

The results of radiotherapy for orbital pseudotumor.

Between January 1982 and March 1987, 23 patients (26 orbits) were treated for orbital pseudotumor with radiation therapy at the Department of Radiation Oncology, Hospital of the University of Pennsylvania. The patients were referred for clinical relapse after steroid taper in 70%, no response to steroids in 17%, and no steroid treatment (refused or contraindicated) in 13%. Presenting symptoms/signs included soft tissue swelling in 92% of orbits, pain in 92%, proptosis in 85%, and extraocular muscle dysfunction or ptosis in 69%. Decreased visual acuity was seen in only 19% of orbits. Biopsy was performed in nine patients. Treatment consisted of 2000 cGy in 2 weeks in 10 fractions for all patients. Median follow-up was 41 months, with a mean of 53 months, and a range of 21-92 months. Complete response was documented in 87% of orbits with soft tissue swelling, 82% with proptosis, 78% with extraocular muscle dysfunction, and 75% with pain. Of the five patients with visual acuity defects, three experienced complete recovery. There was no difference in complete response in patients biopsied versus those not biopsied. Overall, 17 orbits have remained in complete orbital response with no further steroid requirement (66%). Three orbits suffered local relapse at some point following radiation therapy and were retreated with steroids. These three orbits had durable local control off steroids at last follow-up (11%). Therefore, 77% of orbits attained durable local control and were steroid independent with radiation therapy alone or radiation therapy followed by steroids for relapse. Only one patient developed systemic lymphoma with follow-up. No pretreatment clinical factor reached statistical significance with respect to prognosis following radiation therapy at the less than or equal to .05 level. There were no significant acute or chronic side effects secondary to treatment. Steroids should continue to be first line treatment for orbital pseudotumor, but radiation therapy has a well-defined role in cases of steroid failure or in patients unable to tolerate steroid therapy.