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Background: The objective of this study was to document previously unreported anemia in prostate cancer patients treated with neoadjuvant combined androgen blockade (CAB) and pelvic radiotherapy (XRT)., Methods: Four institutions treated 141 patients (mean age +/- SD, 70.9 +/- 6.5 years) with zoladex 3.6 mg injection subcutaneous depot monthly and flutamide 250 mg orally three times per day for 2 months (CAB), followed by zoladex and flutamide with concurrent XRT (65-70 Gy) for 7-8 weeks., Results: After the XRT, the patients were randomized to receive no further treatment (Z- group, 71 patients) or zoladex alone (Z+ group, 70 patients) for 2 years. Hemoglobin (Hb) levels decreased > or = 1 g/dl (mean +/- SE, 2.1 +/- 0.1 g/dl) in 98/131 patients (75%) after 2 months of CAB, and > or = 2 g/dl (3.1 +/- 0.1 g/dl; range, 0.1-6.8 g/dl) in 106/131 patients (81%) after an additional 2 months of CAB with concurrent XRT. The decrease in Hb levels paralleled the decreased in testosterone levels. No evidence of blood loss or hemolysis was found., Conclusions: There was no association between incidence or rate of Hb decrease and race, age, or pretreatment prostate-specific antigen (PSA) levels. However, the recovery from anemia after completion of CAB in African-Americans was slower than in Whites in the Z+ group (P < 0.04). Whereas grade 1 hematologic toxicity may occur in < 5% of the patients with zoladex alone, and approximately 6% with flutamide alone, in our study 81% showed mild to pronounced anemia. Since anemia has not been observed after treatment with XRT alone or XRT followed by zoladex, we conclude that the anemia was due to CAB. Recognition of this side effect should avoid unnecessary diagnostic evaluations.

Background: In this article the authors report an analysis and long term results of delayed/salvage radiation therapy administered to asymptomatic patients who had an elevated prostate specific antigen (PSA) level, many months to many years after radical prostatectomy., Methods: During 1987 to 1990, 40 asymptomatic patients were found to have an elevated PSA level 9 to 96 months after radical prostatectomy. The patients underwent transrectal needle aspiration biopsy of the urethrovesicle junction anastomosis (uvj); 28 patients had a positive biopsy and 12 patients had a negative biopsy. Delayed/salvage radiation therapy was administered to the pelvis (45 Gray [Gy]) and prostate bed (59.5 Gy), including the uvj., Results: Twenty-four of 37 patients (65%) were free of clinical disease. In 10 patients (27%), the radiation therapy resulted in a durable decrease in the elevated PSA level below a detectable level for a minimum 5-year follow-up. Five patients were alive with clinical disease. Eight died of disease. Three patients were lost to follow-up., Conclusions: This experience shows that delayed/salvage radiation therapy to the pelvis (45 Gy) and prostate bed (59.5 Gy), even many years after radical prostatectomy for pathologic stage pB, pC, and pD1 carcinoma of the prostate, was well tolerated and provided freedom from clinical disease in 24 of 37 patients (65%), and a decrease in elevated PSA level in 10 patients (27%). Delayed/salvage radiation therapy appears to be beneficial for patients who had undergone radical prostatectomy only and then developed rising PSA levels during the follow-up period.

Extramedullary myeloid cell tumors are rare manifestations of acute nonlymphocytic leukemia (ANLL). While many advances in diagnosis have been made, dilemmas remain concerning the treatment of this disease. In primary extramedullary leukemia (EML) most reports agree upon a local therapy followed by systemic chemotherapy such as is used for ANLL. However, further prophylactic local or systemic therapy with stem cell support remains controversial. A 20-year-old patient was diagnosed as having granulocytic sarcoma (GS) of the uterus without evidence of ANLL in 1991. After resection of the tumor at the uterine cervix and chemotherapy with daunorubicin 50 mg/m2 (days 1-3) and cytosine-arabinoside 200 mg/m2 (days 1-7) in September 1991, complete remission was achieved. In October 1991 cytosine-arabinoside 1000 mg/m2 every 12 h from day 1 to day 6 and amsacrine 200 mg from day 5 to day 7 were given as consolidation. Two years later relapse occurred in the adnexae. After radical hysterectomy, the same induction and consolidation chemotherapy was administrated. Subsequently, cytoxane 60 mg/m2 and fractionated total body irradiation (6 x 200 cGy) were given as conditioning and the previously cryopreserved bone marrow was reinfused. Finally, after hematopoietic engraftment, prophylactic local irradiation (4500 cGy) to the pelvis was given resulting in a disease-free long-term survival of more than 36 months after relapse. Although this experience is confined to one patient, it may contribute to the design of prospective therapeutic studies in patients with primary EML.

Background: The objective of this study was to evaluate the feasibility, morbidity, and efficacy of unilateral laparoscopic ovarian transposition on the preservation of hormonal function in premenopausal patients requiring pelvic irradiation (external and/or intracavity by brachytherapy)., Methods: This prospective study was based on 20 patients: 17 presenting with cervical cancer, 2 with Hodgkin's disease, and 1 with ependymoma of the cauda equina. The operative technique consisted of releasing the right ovary from its pelvic attachments, and placing it as high and as laterally as possible in the right paracolic gutter, after creating a pedicle on the infundibulopelvic ligament. The follow-up of ovarian function was more than 1 year for 14 patients., Results: The therapeutic protocol was not modified as a result of ovarian transposition. No intraoperative or postoperative complications were observed. The mean dose of irradiation received by the transposed ovary was 1.75 gray (Gy) (range 0.4-3.7). Mean follow-up was 2 years. Two cases of menopause (14.7%), in the only 2 patients older than 40 years, were observed among the 14 patients followed for more than 1 year. The success rate was 100% for patients younger than age 40 years., Conclusions: Laparoscopic ovarian transposition is a simple and reliable method, which does not complicate subsequent therapeutic protocol. Its short term efficiency is comparable to results obtained by laparotomy, with a lesser morbidity. Although long term evaluation is necessary, laparoscopic surgery should be considered as an alternative to laparotomy for ovarian transposition.

Most patients with ovarian cancer require further therapy with chemotherapy or radiotherapy because of the high recurrence risk following surgery alone. Radiotherapy directed to the whole abdomen and pelvis is capable of producing survival rates of 70% in carefully selected patients. Such patients have no more than microscopic residual disease in the abdomen, and small volume residual disease in the pelvis. They are selected based on a prognostic matrix which considers grade, stage and the presence of pelvic residual disease. With optimal radiotherapy technique, long term serious toxicity occurs in less than 5% of patients. Patients with macroscopic residual disease are treated with chemotherapy. Patients who obtain a complete response have been treated with consolidative whole abdominal radiotherapy, although the benefit of such an approach is unclear.

Purpose: To present the findings of the irradiated noncritical soft tissues of the female pelvis at magnetic resonance (MR) imaging within 18 months after radiation therapy (RT)., Materials and Methods: The soft tissues of the pelvis of 24 women with advanced cervical carcinoma were studied in 240 MR examinations scheduled before, three times during, and 7 weeks and 3, 6, 9, 12 and 18 months after RT. Two radiologists visually evaluated the signal intensity (SI) of the subcutaneous fat, muscles, and presacral space (PS) on T1- and T2-weighted and short inversion time inversion-recovery images., Results: SI compatible with edema appeared in the PS, pelvic muscles, and subcutaneous fat within 3 months after the end of RT and was observed in 23 (96%) of the 24 patients. During the observation period, the edema subsided. Eighteen months after treatment, edema in the PS was seen in 12 (50%) of the 24 patients., Conclusion: The soft tissues of the female pelvis showed a characteristic pattern of varying edema after irradiation.

Artificial X-rays were first produced in Germany in 1895 and used for cancer almost immediately. During the century since this remarkable discovery, radiation therapy has now become the most imporantant non-surgical modality in cancer: over 50% of all cancer patients now receive radiotherapy at some point during the illness. Radiation therapy has increasingly replaced surgical resection for primary control of a variety of solid tumours, particularly where surgical excision is accompanied by severe long-term tissue loss or psychological morbidity. Frequent examples include cancers of the breast, head and neck (especially larynx, naso- and other pharyngeal sites), and locally advanced cancer of the cervix. Combinations of surgery and radiotherapy are increasing used, for example in the preferred management of most cancers of the breast, by wide local surgical excision, breast preservation and postoperative radiotherapy. In rectal carcinoma as well, there is clear evidence of survival improvement in locally advanced cases when surgical excision is followed by routine pelvic irradiation. In other circumstances, radiation is routinely combined with chemotherapy, as for example in the standard management of small cell lung cancer. Anal carcinoma is also best treated by radical radiochemotherapy, avoiding surgical excision (with permanent colostomy) in the majority of patients. In both the developed and developing world, these are all common tumours, with the result that in 1990, almost half a million patients were treated with radiation therapy in the United States of America. Recent technical advances, both in imaging and therapy beam precision, have greatly improved the therapeutic ratio and accuracy of modern radiotherapy. Radiation therapy continues to progress on a rational scientific basis, with a secure clinical role for the foreseable future.

Objective: To compare the clinical efficacy of adjuvant chemotherapy a lone vs chemotherapy plus whole pelvic radiation therapy (RT) on recurrence rates, patterns of recurrence, and survival of patients post-RH-PLND for cervical cancer at high risk for recurrence., Methods: Prospective multicenter randomized Phase III trial. Patients with Stage IB-IIA cervical cancer undergoing RH-PLND were eligible. Risk factors include deep cervical invasion, tumor > or = 4 cm, parametrial involvement, nonsquamous histology, and/or pelvic lymph node metastasis. Chemotherapy consisted of cisplatin and bleomycin, alone or in combination with whole pelvic RT. Survival was determined by Kaplan-Meier estimate., Results: Eighty-nine patients were entered from 1987 to 1994. Seventy-five patients had a Stage IB cancer and 14 patients had Stage IIA. Twenty-five patients had > or = 3 risk factors. Forty-four patients received chemotherapy alone vs 45 patients treated with chemotherapy and RT. Nineteen patients had recurrences and 16 patients have died. Nine of 44 (20%) patients receiving chemo alone recurred compared to 10/45 (22%) patients receiving chemo and RT (P=ns). Patterns of recurrence were statistically similar between the two treatment arms, even among the subgroup of patients with > or = 3 risk factors. Both regimens were well tolerated., Conclusion: CT + RT did not prove a superior adjuvant therapy for patients at high risk of recurrence after RH-PLND for early cervical cancer in this limited trial. Recurrence rates and patterns of recurrences (local, regional, or distant) were not influenced by the addition of RT.

Purpose: To evaluate the relative frequency and magnitude of intratreatment and intertreatment displacements in the patient positioning for pelvic radiotherapy using electronic portal imaging., Methods and Materials: Five hundred ninety-four electronic portal images of seven patients treated with a four-field pelvic technique were evaluated. All patients were treated prone without an immobilization device. Two fields were treated per day, from which an average of two electronic portal images were obtained for each field. No treatment was interrupted or adjusted on the basis of these images. Each image was aligned to the corresponding simulation film to measure the displacements in the mediolateral, craniocaudal, and anteroposterior directions relative to the simulated center. The intertreatment displacement was the displacement measured from the initial image for each daily treated field. For each daily treated field the intratreatment displacement was calculated by subtracting the displacement measured on the initial image from the displacement measured on the final image., Results: The frequency of the intertreatment displacements exceeding 10 mm was 3%, 16%, and 23% for the mediolateral, craniocaudal, and anteroposterior translations, respectively. There were no intratreatment displacements exceeding 10mm (p < 0.001). The frequency of intertreatment displacements exceeded 5 mm was 40, 52, and 51% for the mediolateral, craniocaudal, and anteroposterior translations, respectively; whereas, the frequency of intratreatment displacements exceeding 5 mm was 1, 5, and 7% for the same translations, respectively (p < 0.001). The standard deviation of the intertreatment displacements was at least three times as great as the standard deviation of the intratreatment displacements for all translations. These deviations were greater than the precision limit of the measurement technique, which is approximately 1mm. Each patient had one direction where systematic error predominated in intertreatment positioning. Random error predominated for intratreatment positioning and for the other two directions in intertreatment positioning., Conclusions: During a course of pelvic radiotherapy, the frequency of intertreatment displacements exceeding 5 and 10 mm is significantly greater than the frequency of intratreatment displacements of these magnitudes. Errors in intertreatment positioning are predominantly systematic in one direction for each patient, whereas intratreatment error is predominantly random. Because patients do not move considerably during the daily treatment of a pelvic field, a single electronic portal image per daily field may be considered representative of the treated position.

Gross haematuria and severe bleeding from the large intestine occurred after pelvic radiotherapy in an 84-year-old woman with cancer of the uterus. Hyperbaric oxygenation treatment at 2 atmospheric absolute pressures for 60 minutes daily over 30 days and infusion of prostaglandin E1 abolished completely haematuria and tarry stool, and reversed the endoscopic findings of radiation cystitis and colitis.

Pelvic radiation remains the mainstay in the treatment of many malignancies. Chronic radiation injury represents an obliterative endarteritis. The purpose of our experiment was to investigate the chronic changes in blood flow that occurred in a model of pelvic radiation. Also, we investigated the potential benefits of an elemental diet, sodium meclofenamate, and vitamin A within the radiated large and small bowel. Female Sprague-Dawley rats, 200-250 g, were anesthetized and received 900 rads once a week for 5 weeks for a total of 4500 rads. Group B received sodium meclofenamate, group C elemental diet, and group D vitamin A. Group A received radiation only where control animals (group E) received anesthesia but no radiation. All animals were given treatments during the course of radiation therapy only. Blood flow was determined within the terminal ileum, proximal jejunum, and distal colon 1 week, 5 weeks, 6 months, and 1 year postradiation therapy. Blood flow was determined by strontium-labeled 15-microns microspheres. Results showed that radiation resulted in an increase in blood flow within the terminal ileum at 1 week postradiation of approximately 175% when compared to controls. Blood flow then decreased (59%) when compared to controls at 5 weeks and increased (141%) again at 6 months when compared to controls. No change in blood flow was noted at 1 year postradiation therapy. An elemental diet and sodium meclofenamate prevented these changes in blood flow at each of these times points. No change in blood flow was seen at any of the time points measured within the jejunum or colon.

In our institute, we have developed an electronic portal imaging system based on a matrix of 256 x 256 ionisation chambers. By improvements to the electronics, the system produces images with the same quality as the original system but 3-10 times faster. Software for automatic image analysis has been applied to more than 10,000 images over the last two years. Using an off-line correction strategy, the systematic patient set-up error has been limited to 5 mm or less for 98% of the patients treated for prostate cancer.

Objective: The purpose of this retrospective analysis of 34 patients with stage III ovarian carcinoma was to review results and morbidity of whole abdominal irradiation after surgery and chemotherapy., Methods and Materials: All of the 34 patients had reached a complete clinical remission after first cytoreductive surgery and chemotherapy. After second-look laparotomy each patient underwent whole abdominal irradiation. Except for two patients with chronic myelosuppression, the dose administered was of 22.5 Gy to the abdominal cavity with a boost of 22.5 Gy added to the pelvis., Results: Three and 5-year overall survival rates were 62% and 43%, respectively. Three and 5-year disease-free survival rates were 53% and 38%. Twenty-three patients (68%) developed local relapse or local disease progression. Metastasis occurred in five cases and were always associated with an abdominal cavity recurrence. Residual disease after first cytoreductive surgery appeared as a prognostic factor in univariate analysis. Patients with unresected residuum had a 5-year survival probability of 35% versus 83% for patients without residual disease. We observed 12% grade-3 intestinal toxicities and one fatal case of radiation enteritis., Conclusion: Despite its curative potential, the long term benefit of whole abdominal irradiation in the multimodality treatment of advanced ovarian carcinoma must be evaluated in well designed controlled trials.

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.

A total of 216 midstream urine (MSU) samples from 36 patients with gynecological malignancies undergoing external pelvic radiotherapy (RT) were studied periodically every week for any evidence of urinary tract infection (UTI). UTI was detected in 33.3% patients of whom 8.3% had infection at the onset of RT and the rest developed UTI during the course of therapy. All three patients who had UTI at the onset of RT underwent cystoscopy as a part of routine pretreatment workup. A higher preponderance of UTI was observed in patients of stage III carcinoma cervix (33.3%) compared to stage II (16.7%) during the course of RT. Half of the patients with UTI had repeated episodes of infection despite appropriate antibiotic treatment. The study emphasizes the importance of conducting periodic MSU examination in patients with gynecological malignancies during RT and its treatment with appropriate antibiotics to minimize the risks of further injury to the already susceptible uroepithelium following radiotherapy.

A portal imaging system has been used, in conjunction with a movie measurement technique to measure set-up errors for 15 patients treated with radiotherapy of the pelvis and for 12 patients treated with radiotherapy of the brain. The pelvic patients were treated without fixation devices and the brain patients were treated with individually-moulded plastic shells. As would be expected the brain treatments were found to be more accurate than the pelvic treatments. Results are presented in terms of five error types: random error from treatment to treatment, error between mean treatment position and simulation position, random simulation error, systematic simulator-to-treatment errors and total treatment error. For the brain patients the simulation-to-treatment error predominates and random treatment errors were small (95% < or = 3 mm, 77% < or = 1.5 mm). Vector components of the systematic simulation-to-treatment errors were 1-2 mm with maximal random simulation error of +/- 5 mm (2 S.D.). There is much interest in the number of verification films necessary to evaluate treatment accuracy. These results indicate that one check film performed at the first treatment is likely to be sufficient for set-up evaluation. For the pelvis the random treatment error is larger (95% < or = 4.5 mm, 87% < or = 3 mm). The systematic simulation-to-treatment error is up to 3 mm and the maximal random simulation error is +/- 6 mm (2 S.D.). Thus corrections made solely on the basis of a first day check film may not be sufficient for adequate set-up evaluation.

Urinary fistulae and obstruction following pelvic exenteration are frequent and life-threatening complications. They increase the mortality and morbidity rates of large exereses performed during pelvic exenteration for gynecological cancers. From a series of 97 patients who underwent pelvic exenteration for gynecological cancers we report the incidence, risk factors, and management of major urinary complications. Eighty patients had had previous surgery and/or pelvic radiation therapy at the time of pelvic exenteration. A urinary diversion was performed in 63 patients. Major early urinary complications were: urinary fistula in seven patients and ureteral obstruction in four patients (11.3% of the patients). Ten patients had a late urinary complication: stenosis of the cutaneous ureteral meatus (five), stenosis of the ureteroileal anastomosis following ileal loop (two), and urinary fistulae (three). Cancer recurrence was found in 4 of these 10 cases. Major early urinary complications were significantly increased in patients who had received previous pelvic radiation therapy (P < 0.05) and in patients who had had an intestinal conduit for urinary diversion (P < 0.05). Reoperation was done in six of seven cases of early urinary fistula (urinary undiversion four, nephrectomy one, ureteral reimplantation one). Three of four ureteral obstructions were managed with percutaneous nephrostomy and ureteral stent. We recommend the use of nonirradiated bowel segment for urinary diversion as transverse colon or jejunal conduit in patients who have received previous high doses of pelvic radiotherapy. For the management of urinary complications post pelvic exenteration, reoperation is required for most urinary fistula but ureteral obstructions can be managed with percutaneous nephrostomy and ureteral stent.

Purpose: Pelvic radiation is standard treatment for women with stage IIb to IVa cervical cancer, but treatment results are disappointing, particularly for women with bulky tumors. We investigated the role of primary chemotherapy followed by pelvic radiotherapy in a randomized trial., Patients and Methods: Two hundred sixty patients with stage IIb and IVa cervical cancer received either standard pelvic radiotherapy or primary chemotherapy with cisplatin 60 mg/m2 and epirubicin 110 mg/m2 administered at 3-week intervals for three cycles, followed by pelvic radiotherapy., Results: Ninety-nine patients have relapsed with a median follow-up duration of 1.3 years; in 62 patients, the first site of progressive disease was the pelvis. Patients who received primary chemotherapy had a significantly higher pelvic failure rate than those who received radiotherapy alone (P < .003). Seventy-six patients have died, and those who received primary chemotherapy had significantly inferior survival compared with those who received radiotherapy alone (P = .02). Tumor response following chemotherapy was observed in 63%. After radiotherapy, tumor response occurred in 72% of those who received combined modality treatment, compared with 92% of those who received radiotherapy alone., Conclusion: Primary chemotherapy with epirubicin and cisplatin, although resulting in tumor response in a significant proportion of patients, is accompanied by an inferior local control rate and survival compared with standard pelvic radiotherapy alone.

The authors describe a new technique for radioprotection of pelvic viscera by placement of expanders in the subperitoneal area before irradiation of pelvic tumors. They use round shape sub-cutaneous expanders, the volume corresponding to children's weight. Seven patients were treated with excellent results, and minor complications: 2 rectitis due to unsatisfactory displacement of rectum by the balloon. There were no complications related to the device itself. The prosthesis was easy to withdraw. This method seems a safe and effective technique in protecting viscera.

A patient with a history of pelvic radiation therapy for seminoma presented with a prostatic tumor, which appeared predominantly of high signal intensity on T2-weighted magnetic resonance images; low-signal-intensity tissue also extended to the pelvic sidewall. At surgical pathology, the tumor was determined to be radiation-induced sarcoma of the prostate, and the extraprostatic tissue was postradiation fibrosis.

Purpose: To determine whether "standard" lateral pelvic radiation therapy portals provide adequate margins for treating the external iliac lymph nodes (EILNs)., Materials and Methods: With computed tomographic (CT) data and a computerized algorithm, the course of the EILN chain was reconstructed in 48 patients. The marginal distance between a consistently localized portion of the EILNs and the anterior field border that was placed at the front of the pubic symphysis was recorded for each patient., Results: The EILNs were covered adequately in only 50% of both men and women. More adequate EILN margins were observed in (a) women older than 68 years, (b) women with small anteroposterior separations, (c) men older than 70 years, and (d) men and women with a low central obesity index. Less adequate margins were observed in men who were obese or men with large anteroposterior separations. In the study population, no correlation was observed for sex, race, or tumor site., Conclusion: The authors recommend portals that are designed specifically for patients rather than standard portals that may inadequately cover the intended targets.

Purpose: Radiotherapy induced diarrhea and convulsive pain are severe side-effects of irradiation of the pelvis and the abdomen leading often to an interruption of the treatment. Up to now these side-effects were only treated symptomatically, prophylactic therapies are not known., Patients and Methods: During the years 1992 and 1993 174 patients who obtained radiotherapy in the pelvis or the abdomen because of different malignancies were observed referring to the diarrhea-prophylactic effect of Smectite (= Skilpin). 80 patients received Smectite at the beginning of radiotherapy, 94 patients of the control group were treated with motility modifying drugs when diarrhea appeared. The following parameters were compared: Frequency, consistence and incontinence of stool, tenesmus and the onset of diarrhea., Results: 67.0% (n = 63) of the patients in the control group developed diarrhea, whereas in the pretreated Smectite-group only 37.5% of the cases (n = 30) developed diarrhea. The first appearance of diarrhea was at day 17 in the pretreated group and averagely at day 11 in the control group. 44% of the patients in the control group suffered from tenesmus versus 25% in the Smectite-group., Conclusion: In comparison to the symptomatic treatment of radiation enteritis the prophylactic application of Smectite is able to reduce the diarrhea from the beginning of radiotherapy or at least to reduce the pathological frequency of stool and therefore to increase the quality of life.

Purpose: We describe the experimental demonstration of the delivery of a three-dimensional conformal radiotherapy dose distribution using in-field modulation of nine fixed-gantry fields., Methods and Materials: Two-dimensional in-field modulation profiles, varying from field to field, were realized by quasi-dynamic multileaf collimation using the prototype of a commercially available multileaf collimator installed on a medical linear accelerator. The profiles were calculated to deliver an optimal dose distribution for a patient with a prostate carcinoma. The target volume surface was invaginated and bifurcated. The calculated dose distribution was delivered to a homogeneous polystyrene phantom consisting of 1 cm thick slices that were cut to match the patient's outer contour. Seven therapy verification films were placed between the phantom slices., Results: Analysis of the films revealed a degree of conformation of the high-dose region to the target shape that would not be possible with unmodulated conformal therapy. However, small observed spatial displacements of the dose distribution confirm the need for very accurate positioning., Conclusions: It is feasible to deliver clinically relevant, three-dimensional dose distributions that conform to invaginated and bifurcated target volumes using fields modulated by multileaf collimators.

Purpose: Radiation has become an adjunct in the treatment of pelvic malignancies. Attempts to prevent adjacent tissue injury have met with varying degrees of success, and the purpose of this study was to investigate potential radioprotective effects of an elemental diet, sodium meclofenamate, and vitamin A in an animal model of acute and chronic pelvic radiation previously described., Methods: Female Sprague-Dawley rats, 200-250 grams, were anesthetized and then received 900 rads of pelvic radiation once per week for five weeks for a total of 4500 rads. Animals were divided into five groups. Treatment groups received radiation and elemental diet, radiation and vitamin A, radiation and sodium meclofenamate. Control animals received anesthesia only and no radiation. Vitamin A was given as a supplement to (662 IU/kg) standard rat chow. Elemental diet was given as a commercially available formula, whereas sodium meclofenamate was given as a postoperative supplement (5 mg/kg/day). All animals were given these treatments during the course of radiation therapy only. Histology of distal colon was measured at one week, five weeks, six months, and one year postradiation therapy. The distal two cm of colon were removed at necropsy and fixed in 10 percent formalin at each of the above time points. Histologic grade was determined by a previously described grading scale., Results: Results showed a qualitative radiation injury that could be documented at one and five weeks postradiation. Elemental diet, vitamin A, and sodium meclofenamate prevented histologic changes that occurred at these time points. No difference in histologic grade was seen between any groups at six months and one year postradiation therapy., Conclusion: In summary, our model of pelvic radiation produces a definable radiation injury within the colon at one and five weeks postradiation. Use of elemental diet, vitamin A, and sodium meclofenamate prevented these changes.

Extended radionecrosis in the pelvic area is a disaster occurring in a minority of patients treated with radiotherapy. Extensive excisional procedures, including pelvic exenteration, have been recommended, but carry high morbidity and mortality rates. Alternative treatment strategies are needed to improve survival and increase the quality of life in these patients. We retrospectively analysed the charts of eight patients treated for radionecrosis in the pelvic area between 1985 and 1991. During this period deviatory procedures, repeated but limited debridement and the early incorporation of an omental flap in the ischemic area were used in an attempt to avoid exenteration, but effectively stop further progression of infection and necrosis. The patients underwent a median of five surgical interventions (range: 2 to 21) for 10 sites of radionecrosis. The total of 61 procedures consisted of debridement (29), omental pedicle grafting (6), deviation of urinary tract (3) or intestinal tract (4) and including procedures due to complications (21). They were hospitalized for a median duration of 95 days (range 43-155) divided over several admissions (median 3, range 2-8). One patient died of sepsis during treatment. Complete recovery was achieved in all surviving patients with a median of 12 months (range: 9 to 20 months) after initial surgery. Early surgery, the limited extent of the procedures and omental transposition were the main components of our approach. We conclude that this approach has an acceptable morbidity and mortality rate, while a relatively good quality of life is achieved.

Purpose: Recent studies have suggested that pentoxifylline, a methylxanthine, can prevent or ameliorate late radiation injury in animals and humans. Caffeine is a commonly consumed methylxanthine that provides a model for evaluating the impact of this category of drugs on radiation injury. A retrospective study was undertaken to determine if there is an association between caffeine consumption and a lower incidence of late radiation toxicity., Methods and Materials: From 1984 through 1990, 82 patients with cervical cancer and 53 patients with endometrial cancer were treated with primary or adjuvant radiation therapy at the University of Washington. Patients were interviewed regarding ingestion of caffeine-containing beverages, and average daily caffeine consumption during the time of radiotherapy was estimated. The evaluable patients (42 cervical, 31 endometrial) were stratified by quantity of caffeine consumption for correlation with the incidence of radiation toxicity., Results: Acute radiation toxicity was not associated with caffeine consumption for cervical or endometrial cancer. There was a nonstatistically significant trend toward a decrease in overall late radiation toxicity with increased caffeine intake for cervical cancer patients. Subgroup analysis revealed this trend to be attributable to a decreased incidence of severe late radiation injury in cervical cancer patients who consumed higher levels of caffeine at the time of their radiotherapy (p = 0.02). This relationship was not observable for late toxicity in the endometrial cancer patients due to the low incidence of severe late injury following radiation for that disease., Conclusions: This investigation is supportive of previous studies showing a radioprotective effect for pentoxifylline, and suggests that the mechanisms of radioprotection may be common to methylxanthines as a drug class.

Pyomyositis, an unusual infection of large skeletal muscles, developed in a woman with a history of bulky stage IIIB cervical cancer. Three years prior, the woman had undergone aggressive neoadjuvant intra-arterial chemotherapy followed by pelvic irradiation. The overwhelming majority of pyomyositis cases is caused by Staphylococcus aureus. Group B beta-hemolytic streptococcus, an organism that rarely causes this infection, was isolated in this case. Although surgical drainage is the most common approach, successful percutaneous drainage was accomplished. Pyomyositis has only recently been reported in non-tropical climates. The presentation, diagnosis, risk factors, and management of pyomyositis are discussed.

The authors describe data on the course of pregnancy, delivery and subsequent development of 20 children born to parents treated for Hodgkin's disease. Thirteen women in the clinical stage II and III were delivered of 16 infants (10 daughters and 6 sons) and three men (II A and III A) had four daughters. The parents were in one case treated by irradiation only, twice by chemotherapy only and thirteen times by a combination of irradiation and chemotherapy (COPP/ABVD). The gestation period, parameters of the infants at delivery and the subsequent physical and mental development are normal. In one instance (a girl, now ten and a half years old) the child was born with malformations of the extremities; according to the geneticist this is not related to the previous treatment of the mother. The second child (a son) of this mother is normal. The authors are of the opinion and apply it in the therapeutic protocol in patients of fertile age and do not irradiate nodes in the pelvic region. In treated patients they allow pregnancy only after three or preferably five years following terminated treatment. Survival of patients in the whole group (269 subjects) regardless of age and clinical stage is 75%. The authors are processing a data base of Hodgkin patients since 1968.

Purpose: The following study was done to evaluate the therapeutic value of radiotherapy as an adjunct to surgery for rectal cancer patients., Methods: One-hundred twenty-four patients underwent curative resection by one surgeon (RC) from 1982 to 1991. Forty patients received combined preoperative and postoperative (sandwich) radiotherapy, 30 patients received postoperative radiotherapy, and 54 patients were treated by surgery alone. During the study period sandwich radiotherapy was primarily offered as a free treatment option for patients with tumors which were believed to be transmurally invasive, whereas postoperative radiotherapy was an alternative therapeutic option offered to patients with tumor classified as Dukes B and C at histopathologic examination., Results: Operative mortality was 2 percent in the sandwich radiotherapy group vs. 7 percent in the surgery alone group. After a median follow-up of 60 months, the actuarial locoregional recurrence rate at five years was 3 percent for the sandwich radiotherapy group compared with 18 and 30 percent for the postoperative radiotherapy and surgery alone groups, respectively (P = 0.019). A multivariate analysis using the Cox model confirmed the favorable independent influence of sandwich radiotherapy on local tumor control, especially in distal tumors. The therapeutic benefit of sandwich radiotherapy translated into increased survival in the low-rectum Dukes B subgroup of patients. The actuarial five-year survival rates were 86 percent, 50 percent, and 28 percent in the sandwich radiotherapy, postoperative radiotherapy and surgery alone groups, respectively (P = 0.05)., Conclusions: Preoperative radiotherapy has a significant effect on the prognosis of rectal cancer patients.

Purpose: To assess the possible impact of various treatment factors including split-course versus continuous course treatment on the incidence of chronic bowel complications in patients receiving adjuvant pelvic radiotherapy., Methods and Materials: A retrospective review was performed of records of 153 patients treated with adjuvant external beam pelvic radiation therapy without brachytherapy for endometrial and colorectal carcinomas. Continuous course radiotherapy was administered in 91 patients (59%) and 62 patients (41%) received split course treatment with a planned 2 week mid-treatment break. Mean pelvic dose and daily fraction size were 51.4 and 1.71 Gray, respectively. Multiple patient and treatment variables were assessed for their possible relationship to chronic bowel complications. Univariate and multivariate statistical analyses were carried out., Results: Twenty-seven patients (18%) developed chronic bowel complications at a median interval of 12 months after radiotherapy. Of all factors analyzed, only the use of split course technique was associated with a significantly higher rate of chronic bowel injury and decreased complication-free survival (p = 0.009)., Conclusion: This study supports earlier suggestions that the use of split course rather than continuous course pelvic radiotherapy can increase late intestinal complication rates. Possible pathophysiologic mechanisms are discussed.

A total of 210 patients receiving pelvic radiotherapy were prescribed trimethoprim 200 mg p.o. daily for the duration of radiotherapy. It was prescribed after two mid-stream urine specimens were obtained. Two patients refused to take trimethoprim. The incidence of urinary tract infection prior to starting radiotherapy and trimethoprim was 24% (50 patients). Of these 50 initial infections, eight (16%) were resistant to trimethoprim, necessitating a change to an antibiotic to which the organism was sensitive. Persistent infection occurred in 21 of these 50 patients; 14 (67%) of these infections were resistant to trimethoprim. Of the 160 patients with no initial infection, 25 subsequently developed a urinary tract infection, in spite of prophylactic trimethoprim. Seven of these 25 infections (28%) were resistant to trimethoprim. Prophylactic trimethoprim is not worthwhile for preventing urinary tract infection during pelvic radiotherapy. Eight patients (4%) developed a rash while on trimethoprim, necessitating stopping the drug. Fastidious or anaerobic organisms were isolated in only 15 patients prior to radiotherapy and in seven patients during radiotherapy. Twenty of these 22 patients were female. The organism most commonly isolated was Streptococcus sp. The bacteriuria occurring with these organisms may have resulted from contamination from the vagina.

In a previously published study we compared the outcome probability within 3 years after diagnosis in two groups of advanced ovarian carcinoma patients in complete clinical remission with minimal or no residual disease at second look laparotomy, performed after completion of cisplatin based combination chemotherapy. One group (n = 18) received after reexploration, abdominopelvic irradiation (RT group), the other diagnosed during a later period (n = 19), received after reexploration three courses of introperitoneal cisplatin chemotherapy with systemic thiosulfate protection (IP) group). In the present study the outcome of the same patients is compared after they have all been followed for at least 5 years or till death. A clear trend towards a more favorable, through statistically not significant, 5 year survival was observed (68%), in the IP group, vs 39% in the RT group (p = 0.07). In patients with a negative second-look laparotomy, the respective 5 year survival rates were 92% and 60% (p = 0.08). While the duration of the progression-free interval was similar in both treatment groups the survival after diagnosis of recurrence was significantly better in the IP group (41% vs 0%, p = 0.03).

Thirty-five patients with persistent or recurrent epithelial ovarian cancer were treated with salvage pelvic or para-aortic radiotherapy for disease limited to the pelvis (29), para-aortic retroperitoneum (5), or vaginal cuff (1). Prior therapy included a median of 3 chemotherapeutic drugs (range, 1-7) over a median of 12 cycles (range, 5-39); 12 patients had received intraperitoneal chemotherapy. The median number of prior laparotomies was 3 (range, 2-5). Including pelvic boosts, the median dose delivered to the treatment field was 4600 cGy (range 4000-7000); 2 patients received additional treatment with a permanent 125I implant. All patients completed therapy, although 5 (14%) with grade 3 toxicity required a treatment break. Late bowel complications unrelated to recurrence occurred in 3 patients (9%). Median actuarial and progression-free survivals for all patients from start of radiotherapy were 40 and 14 months, respectively. At least 16 of 26 (62%) recurrences involved the treatment field. Multiple prognostic factors were evaluated in terms of recurrence, survival, and acute and chronic complications, but no significant prognosticators were detected. These findings indicate that limited-field salvage radiotherapy has an acceptable complication rate and may prolong the symptom-free survival interval in selected patients.

A Monte Carlo computational model has been developed for the study of the performance of anti-scatter grids in diagnostic radiology. It is used here to estimate the scatter in the image plane from soft tissue phantoms (representing the patient) and to calculate image contrast and the mean absorbed dose in the phantom. Different scattering conditions, representative of various examinations, have been investigated: adult lumbar spine; small field radiography and fluoroscopy; adult chest and paediatric pelvis and chest. For each scattering condition, the combinations of tube potential and grid ratio have been found which, for a well designed grid, result in the lowest mean absorbed dose in the phantom for a fixed contrast level. In examinations which generate large amounts of scatter, the use of high grid ratios in combination with high tube potentials is favourable with regard to both mean absorbed dose in the phantom and tube charge. When less scatter is generated, either the grid ratio or the tube potential can be varied to achieve the desired contrast level. High grid ratios require shorter exposure times, but need careful alignment in the beam to prevent primary radiation cut-off. It is shown that the air gap technique can be used to reduce patient dose in examinations with small amounts of scatter, but in combinations with a lower tube potential than when a grid is used.

During the last 3 years the Royal Marsden Hospital (RMH) has conducted a prospective randomised trial of conformal pelvic radiotherapy in which dose/volume data and acute toxicity scores have been determined prospectively. Pending completion of the trial, a preliminary analysis has been undertaken of the volume reductions achieved, and of some of the symptom scores. The average symptom score increased during radiotherapy, more markedly for bowel than bladder symptoms. In comparing total doses of 30-38 Gy with 56-65 Gy, watery bowel motions were more frequent with the higher doses (p = 0.013) but in the high-dose group neither this symptom nor tenesmus correlated with volume of rectum treated to at least 90% of the prescribed dose. We conclude that the assessment of the impact of volume on the level of acute symptoms in pelvic radiotherapy is complex, and requires analysis of a range of symptoms, dose levels and normal-tissue volumes. The degree of symptom reduction from conformal radiotherapy will emerge from the RMH randomised trial within the next 12 months.

MR images of 45 patients who had received radiation therapy for carcinoma of the anus or recurrent carcinoma of the rectum were reviewed with regard to postirradiation changes of the pelvic wall. High signal intensity in bone marrow on T1-weighted images due to fatty replacement was almost always observed. Presacral edema occurred in 7 of 36 patients who were examined 4 to 6 weeks after the end of irradiation and was more frequent at later studies. The pelvic wall muscles showed high signal intensity on T2-weighted images compatible with edema. This finding was most frequent on studies performed more than 6 weeks after the end of irradiation. The changes subsided more than a year after radiation therapy. To avoid an erroneous diagnosis of tumor infiltration into the pelvic wall, it is important to be familiar with the normal postirradiation changes of the presacral space and the muscles.

We report on 6 patients who underwent a new type of continent urinary diversion: the gastroileoileal reservoir. These are a select group of patients who presented with the short bowel syndrome, acidosis, borderline diarrhea and/or severe pelvic radiation, which precluded the use of terminal ileum and the ileocecal segment. Considering these factors, and based on the different functional properties of the stomach as well as the need for a large reservoir, a segment of stomach and proximal ileum was used to construct the reservoir. Four patients have been followed for at least 6 months, with the longest followup being 12 months. Temporary dysphagia requiring hydrogen blockers developed in 1 patient. Results indicate excellent function of the continent urinary system, lack of metabolic complications, absent diarrhea and excellent patient tolerance. This procedure could be a useful alternative in some difficult clinical situations when continent urinary diversion is desirable.

Radiation-associated pelvic wounds should be managed by complete excision of all affected tissues and reconstruction with a vascularized flap. The complex anatomy and function of the perineum and pelvis create a variety of reconstructive demands. This article attempts to demonstrate the diversity of the problems that can occur in this region as well as to describe the varied options for reconstruction.

Purpose: To evaluate the prevalence of disordered gastrointestinal function following therapeutic irradiation., Methods and Materials: Gastrointestinal function was evaluated in 30 randomly selected patients who had received pelvic irradiation for treatment of carcinoma of the cervix between 1 and 6 years previously. Each patient underwent evaluations of (a) gastrointestinal symptoms (b) absorption of bile acid, vitamin B12, lactose and fat (c) gastrointestinal transit: gastric emptying, small intestinal transit and whole gut transit and (d) intestinal permeability. Results were compared with those obtained in 18 normal volunteers., Results: Stool frequency was above the control range in five patients and had increased (p < 0.001) since radiotherapy treatment. Bile acid (p < 0.001) vitamin B12 (p < 0.01) and lactose (p < 0.01) absorption were less in the patients when compared with the control subjects. Bile acid absorption was below the control range in 14 of the 30 patients. Dietary calcium intake was lower (p < 0.05) in those patients with lactose malabsorption. Gastric emptying (p < 0.01) and small intestinal transit (p < 0.01) were more rapid in the patients. Both small intestinal (r = -0.39, p < 0.05) and whole gut (r = -0.45) transit were inversely related to stool frequency. Either bowel frequency, bile acid absorption, vitamin B12 absorption was outside the control range in 19 of the 30 patients., Conclusion: Abnormal gastrointestinal function is essentially an inevitable long-term sequel of pelvic irradiation.

Purpose: Many techniques and devices have been used in an attempt to minimize gastrointestinal morbidity of pelvic irradiation. The value of a temporary intrapelvic tissue expander to displace small bowel from pelvic radiotherapy fields was analyzed by comparing volumetric treatment parameters of patients with and without such a device., Methods and Materials: Between 1983 and 1991, 77 patients with a diagnosis of endometrial (n = 35), colorectal (n = 41), or anal carcinoma (n = 1) received adjuvant postoperative radiotherapy after undergoing treatment planning simulation with the use of small bowel oral contrast medium. Fourteen of these patients underwent surgical placement of a temporary intrapelvic tissue expander prior to radiotherapy, and 63 patients did not. Small bowel volume within the treatment portals was measured for both initial pelvic and conedown fields for all cases, and compared between the two patient groups., Results: The volume of small bowel within the initial pelvic fields receiving full dose irradiation was significantly less among patients with a tissue expander. For patients with a tissue expander, mean volume receiving full dose irradiation was 25 cm3 (median 0 cm3, range 0-297 cm3), whereas the corresponding volume was 239 cm3 (median 181 cm3, range 0-943 cm3) without a tissue expander (p < .0001). A similar reduction of irradiated small bowel volume was noted in the conedown fields with the use of a tissue expander (p = .07). Volumes receiving less than full dose irradiation were also less within the initial pelvic (p = .0001) and conedown (p = .002) fields with a tissue expander. Multivariate analysis of patient and treatment-related parameters showed the use of a tissue expander to be the only factor correlated with decreased small bowel volume within the treatment field (p = .003). Morbidity related to placement and removal of the tissue expander was acceptable. Acute radiation-related morbidity was significantly less in patients irradiated with a tissue expander in place (p < .001)., Conclusions: Placement of an intrapelvic tissue expander was correlated with decreased small bowel volume within the radiotherapy treatment field. Diminished radiation-induced acute gastrointestinal morbidity was noted with use of a tissue expander.

An electronic portal imaging device (EPID) was used to detect patient setup displacement during the course of a 3-field pelvic irradiation of two groups of patients: 10 rectal and 10 prostate carcinomas. These patients were irradiated with conventional treatment techniques in routine clinical practice. A total of 469 portal images and 60 simulator films were used to determine the values of setup deviations in the X- Y- and Z-directions of a fixed coordinate system, corresponding to the medio-lateral, cranio-caudal and antero-posterior direction, respectively. The absolute displacement averaged over all setups and patients ranged between 0.4 mm and 1.4 mm with a standard deviation (S.D.) of 1.6-3.9 mm. The overall distribution along each direction could be separated into a distribution of random deviations (S.D.s ranging from 1.2 to 2.8 mm) around the mean deviation of each patient and a distribution of the means themselves: the distribution of systematic deviations (S.D.s ranging from 1.0 to 2.6 mm). Significant gradual displacement as a function of time was detected in 5 out of the 20 patients, 2 in the rectum and 3 in the prostate group. This "time trend" was found along each of the 3 directions specified. The magnitude of the time-dependent displacement throughout the course of treatment ranged between 4 and 11 mm. It can be concluded that for treatments requiring a high level of precision, portal images should be made and analyzed during the whole treatment course in order to detect and correct significant time trends.