Audit of suspected chronic intestinal pseudo-obstruction in patients with gynecologic cancer.

PURPOSE: To describe chronic intestinal pseudo-obstruction (IPO) syndromes that occur after radiotherapy or chemotherapy (or both) for gynecologic cancer. METHODS: All 48 patients in the study population had a history of gynecologic cancer, treatment with radiotherapy or chemotherapy (or both), and suspected chronic IPO. The final diagnosis was based on clinical symptoms, radiographic imaging, motility studies, and surgical findings. Treatment was expectant for 27 patients and surgical for 21. RESULTS: In six of the 21 surgical patients, the final diagnosis was mechanical obstruction. In the other 15, it was IPO syndrome: six had an idiopathic dysfunction (ID) and nine had a thick fibrinous coating (FC) on the serosal surface. Intestines of these 15 patients had patent lumens but decreased motility. The ID and FC groups differed in mean age, chemotherapy administration, and mean time from radiotherapy to surgery. Symptoms improved in 67% of FC patients compared with 17% of ID patients. Among patients treated expectantly, symptoms improved in 50% of the ID patients and in 38% of the FC patients. Motility studies were useful for distinguishing ID from FC or mechanical obstruction. CONCLUSION: Clinical history and motility studies may assist in diagnosing IPO syndrome in gynecologic cancer patients treated with radiotherapy or chemotherapy (or both) and in identifying patients who might benefit from surgical intervention.

A prospective, randomized, double-blind, placebo-controlled study of orbital radiotherapy for Graves' ophthalmopathy.

CONTEXT: Although widely used for more than 85 years, the efficacy of radiotherapy for Graves' ophthalmopathy (GO) has not been established convincingly. OBJECTIVE: To evaluate the efficacy of radiotherapy for GO. DESIGN: Prospective, randomized, internally controlled, double-blind clinical trial in a tertiary care academic medical center. PARTICIPANTS: The patients were ethnically diverse males and females over age 30 seen in a referral practice. The patients had moderate, symptomatic Graves' ophthalmopathy (mean clinical activity score, 6.2) but no optic neuropathy, diabetes, recent steroid treatment, previous decompression, or muscle surgery. Forty-two of 53 consecutive patients were enrolled after giving informed consent and fulfilling study entry criteria. Eleven eligible patients declined to participate because of inconvenience, desire for alternative therapy, or concern about radiation. INTERVENTION: One randomly selected orbit was treated with 20 Gy of external beam therapy; sham therapy was given to the other side. Six months later, the therapies were reversed. MAIN OUTCOME MEASURES: Every 3 months for 1 year, we measured the volume of extraocular muscle and fat, proptosis, range of extraocular muscle motion, area of diplopia fields, and lid fissure width. Effective treatment for GO will modify one or more of these parameters. RESULTS: No clinically or statistically significant difference between the treated and untreated orbit was observed in any of the main outcome measures at 6 months. At 12 months, muscle volume and proptosis improved slightly more in the orbit that was treated first. CONCLUSIONS: In this group of patients, representative of those for whom radiotherapy is frequently recommended, we were unable to demonstrate any beneficial therapeutic effect. The slight improvement noted in both orbits at 12 months may be the result of natural remission or of radiotherapy, but the changes are of marginal clinical significance.

Is radiotherapy important for low-grade soft tissue sarcoma of the extremity?

Radiotherapy and limb-preserving surgery has replaced amputation and compartmental resection for treatment of soft tissue sarcomas. However, the role of radiotherapy in low-grade tumors remains unclear. This study reviews the outcomes of 132 patients who received multimodality treatment for low-grade soft tissue sarcoma. Large primary tumors (> 5 cm) and the absence of radiotherapy correlated with local recurrence. Radiotherapy was most effective in patients operated on with marginal margins. Patients who were treated with wide surgical margins or had small tumors (< or =5 cm) showed no benefit with adjuvant radiotherapy. Size greater than 5 cm and local recurrence correlated with metastasis. Radiotherapy appears to be important in the management of low-grade soft tissue sarcoma. The principles of local treatment for low-grade soft tissue sarcoma should be the same as for high-grade tumors with a combination of surgery and adjuvant radiotherapy. In a subset of patients with small and widely excised tumors, consideration may be given to withholding radiotherapy. Local recurrence and metastasis from low-grade soft tissue sarcoma may occur as long as 1 decade after primary tumor resection. Long-term review of patients with low-grade tumors may be indicated.

Clinicopathologic features and treatment of postirradiation sarcoma of bone and soft tissue.

BACKGROUND AND OBJECTIVES: An analysis of the clinicopathologic features and treatment of patients with postirradiation sarcoma of bone and soft tissue was performed to guide modern evaluation and management. METHODS: A retrospective analysis of 135 sarcomas in 130 patients was performed. RESULTS: The mean age of the 130 patients was 48 years, and there was a female predominance because of irradiation for carcinomas of the breast and uterus. Indication for irradiation was a soft tissue lesion (such as lymphoma or breast cancer) in 58.5% of patients and a bone lesion (such as giant cell tumor or fibrous dysplasia) in 41.5%. The latent period (interval between irradiation and discovery of the sarcoma) ranged from 4-55 years (mean, 17 years). Of the lesions, 74% were stage IIB (high-grade extra-compartmental) and 24% were stage III (metastases). Ninety-four patients received their treatment at our institution. Of the 61 patients with resectable disease, 49 had amputations and 12 had limb salvage procedures. The 5-year cumulative survival rate was 68.2% for patients with peripheral (extremities, including proximal femur and hip) resectable lesions and 27.3% for patients with central (pelvis, head/neck, and ribs) resectable lesions. The local recurrence rate correlated with the surgical margin achieved: intralesional, 73%, marginal, 64%, and wide, 23%. CONCLUSIONS: The prognosis for patients with peripheral resectable postirradiation sarcomas is good if a wide surgical margin can be achieved. This group of patients should be treated aggressively because they have a new cancer.

Ductal carcinoma in situ of the breast.

PURPOSE: The increasing incidence and biological heterogeneity of ductal carcinoma in situ (DCIS) of the breast have made the management of this entity challenging and controversial. This paper reviews data on the natural history of the disease and results obtained with various management approaches. DATA SOURCES: Computerized MEDLINE search of articles related to DCIS published since 1966. STUDY SELECTION: Randomized trials were given higher value; however, because these were relatively scarce, retrospective studies and data published in abstract form were also included. DATA EXTRACTION: The authors reviewed all sources critically. No formal statistical calculations were made. DATA SYNTHESIS: The incidence of DCIS is increasing, and a greater proportion of diagnoses are being made in asymptomatic patients. No data from randomized trials compare mastectomy and breast-conserving therapy for the treatment of DCIS. A large randomized trial comparing lumpectomy with lumpectomy plus radiotherapy showed lumpectomy plus radiotherapy to be effective for management of this disease. The presence of comedo necrosis and surgical margin status are frequently used as predictors of subsequent recurrence, although this practice is controversial. The risk for in-breast recurrence at 5 years after lumpectomy and radiotherapy is approximately 8%. With more refined molecular analysis, the relation of DCIS to invasive breast cancer will be better defined. CONCLUSIONS: Treatment strategies for DCIS have evolved, and lumpectomy followed by radiotherapy is an appropriate alternative for most patients. The use of lumpectomy alone in selected patients remains controversial.

Accelerated hyperfractionation radiation therapy after lumpectomy and axillary lymph node dissection in patients with stage I or II breast cancer: pilot study.

PURPOSE: To prospectively assess tolerance to accelerated hyperfractionation radiation therapy in patients undergoing breast-conservation therapy and to exclude, with 90% confidence, a 20% or greater risk of an acute toxic reaction of at least grade 3 (severe). MATERIALS AND METHODS: Thirty-seven patients (aged 33-80 years) with evaluatable cases received 48 Gy in twice-daily 1.6-Gy fractions to the breast and regional lymph nodes (if three or more lymph nodes were involved) and a boost of 9.6 Gy in twice-daily 1.6-Gy fractions. Acute and late effects were scored by using the Radiation Therapy Oncology Group and European Organization for the Research and Treatment of Cancer radiation morbidity criteria. RESULTS: One patient developed a grade 3 acute skin toxic reaction and another grade 3 (continuous) acute edema. There have been no grade 4 (life-threatening) acute toxic reactions, local recurrences, or cancer- or treatment-related deaths. CONCLUSION: This breast-conservation accelerated hyperfractionation radiation therapy schedule is tolerable. Additional follow-up is necessary to determine long-term morbidity and cosmesis, and further study in a larger patient group is necessary to confirm efficacy.

Intraoperative irradiation: current and future status.

Intraoperative radiation therapy (IORT) in its broadest sense refers to the delivery of irradiation at the time of an operation. This article will discusses the rationale for and results of both intraoperative electron radiation therapy and intraoperative high dose rate brachytherapy when used in conjunction with surgical exploration and resection and external beam radiation therapy and chemotherapy. Both IORT methods evolved with similar philosophies as an attempt to achieve higher effective doses of irradiation while dose limiting structures are surgically displaced.

Local control of extra-abdominal desmoid tumors.

We analyzed the records and histopathological specimens of fifty patients who had had a previously untreated desmoid tumor. The patients were followed for at least two years (average, forty-eight months). Three patients had a biopsy and were managed with observation only, and three patients had radiation therapy only. Of the remaining forty-four patients, thirty-four were managed with an operation and ten, with an operation and radiation therapy. In the group that was managed operatively without radiation therapy, the resection was wide in thirteen patients, marginal in nineteen, and intralesional in two. At the most recent follow-up examination, there had been no local recurrence in eleven of the patients who had had a wide resection, ten of the patients who had had a marginal resection, and one of the patients who had had an intralesional resection. Thus, twenty-two (65 per cent) of the thirty-four patients had no local recurrence at the time of the latest follow-up. In the group of ten patients who had been managed with an operation and radiation therapy, eight had no local recurrence: the two who had had a wide resection, three of the four who had had a marginal resection, and three of the four who had had an intralesional resection. None of the fifty patients died of the disease.

Two or six hyperthermia treatments as an adjunct to radiation therapy yield similar tumor responses: results of a randomized trial.

From March 1984 to February 1988, 70 patients with 179 separate treatment fields containing superficially located (less than 3 cm from surface) recurrent or metastatic malignancies were stratified based on tumor size, histology, and prior radiation therapy and enrolled in prospective randomized trials comparing two versus six hyperthermia treatments as an adjunct to standardized courses of radiation therapy. A total of 165 fields completed the combined hyperthermia-radiation therapy protocols and were evaluable for response. No statistically significant differences were observed between the two treatment arms with respect to tumor location; histology; initial tumor volume; patient age and pretreatment performance status; extent of prior radiation therapy, chemotherapy, hormonal therapy, or immunotherapy; or concurrent radiation therapy. The means for all fields of the averaged minimum, maximum, and average measured intratumoral temperatures were 40.2 degrees C, 44.8 degrees C, 42.5 degrees C, respectively, and did not differ significantly between the fields randomized to two or six hyperthermia treatments. The treatment was well tolerated with an acceptable level of complications. At 3 weeks after completion of therapy, complete disappearance of all measurable tumor was noted in 52% of the fields, greater than or equal to 50% tumor reduction was noted in 7% of the fields, less than 50% tumor reduction was noted in 21% of the fields, and continuing regression (monotonic regression to less than 50% of initial volume) was noted in 20% of the fields. No significant differences were noted in tumor responses at 3 weeks for fields randomized to two versus six hyperthermia treatments (p = 0.89). Cox regression analyses were performed to identify pretreatment or treatment parameters that correlated with duration of local control. Tumor histology, concurrent radiation doses, and tumor volume all correlated with duration of local control. The mean of the minimum intratumoral temperatures (less than 41 degrees C vs. greater than or equal to 41 degrees C) was of borderline prognostic significance in the univariate analysis, and added to the power of the best three covariate model. Neither the actual number of hyperthermia treatments administered nor the hyperthermia protocol group (two versus six treatments) correlated with duration of local control. The development of thermotolerance is postulated to be, at least in part, responsible for limiting the effectiveness of multiple closely spaced hyperthermia treatments.

Prognostic factors in the radiotherapy of Graves' ophthalmopathy.

Between April 1968 and February 1988, 311 patients with symptomatic and progressive Graves' ophthalmopathy were treated with megavoltage orbital radiotherapy. The patients were divided into three groups: I (156 patients) treated with 20 Gy/2 weeks; II (69 patients) treated with 30 Gy/3 weeks, and III (a most recent set of 86 patients) received 20 Gy/2 weeks. The degree of eye involvement was evaluated numerically before and after therapy for each of five parameters: soft tissue signs, proptosis, eye muscle impairment, corneal involvement, and sight loss. Pre-treatment and current thyroid diagnosis and status were also noted. To evaluate the effects of radiotherapy alone, follow-up was terminated at the time any eye surgery was done; for those not treated surgically the minimum follow-up was 12 months. Because there were significant demographic differences between the patient groups, the results of each group were analyzed separately. A stepwise linear regression analysis was performed to determine if there were any significant variables affecting outcome. Based on these data formulae were derived which enable outcome to be predicted in any patient. Before therapy more than 90% of patients in all groups had soft tissue and eye muscle involvement, whereas 65-75% had proptosis and about half 50% had some degree of sight loss. Radiotherapy arrested progression of ophthalmic parameters in all but 1-6% of the patients. Objective and symptomatic improvement was noted for all parameters assessed, but there was marked individual variability. The best responses were noted for soft tissue, corneal involvement, and sight loss; however over half the patients had some improvement in eye muscle function and proptosis. Factors which resulted in less favorable outcome included male gender, advanced age, need for concurrent therapy for hyperthyroidism, and no history of hyperthyroidism. No complications have been observed. No significant differences in outcome were observed between the two dosage schedules. Following radiotherapy 29% of patients subsequently underwent some form of eye surgery, mostly eye muscle surgery to correct diplopia. After radiotherapy corticosteroid therapy was stopped without relapse in 76%. Orbital radiotherapy can result in improvement in signs and symptoms of Graves' ophthalmopathy in the majority of patients. For the remainder of patients the disease manifestations can be stabilized to allow functional surgical correction.

Local hyperthermia and radiation therapy in the retreatment of superficially located recurrences in Hodgkin's disease.

Five patients with Hodgkin's disease, nodular sclerosing subtype, who had multiple failures after chemotherapy and radiation therapy were treated for palliation with low-dose radiation therapy and hyperthermia to seven superficially located sites of recurrence. Six of the seven areas were in previously irradiated fields and one was at the margin of the prior radiation therapy field. Local control was obtained for all lesions and was maintained for the duration of the patients survival (5 to 27 months). Four of the five patients expired with no relapse in the area of treatment. One patient remains alive and free of recurrence in his treatment fields. Temperatures were monitored using thermistors, fluoroptic systems or thermocouples manually mapped through closed-end catheters inserted into the tumor and thermal parameters and temperature distributions were calculated. Excellent heating was obtained with 46.4% of monitored intratumoral temperatures greater than or equal to 43 degrees C. The average of the monitored intratumoral temperatures for all treatments (Tave) was 43.2 degrees C; the average of the monitored intratumoral minimal temperatures for all treatments (T min) was 40.1 degrees C, and the average of all monitored intratumoral maximum temperatures (T max) was 46.7 degrees C. In comparison with temperatures obtained in 277 superficially located tumors of other histologies, Tmax was significantly higher in Hodgkin's disease lesions (p = 0.007). The difference in Tave approached significance (p = 0.058). These initial results support the role of radiation therapy and hyperthermia for palliation of isolated superficial recurrences in patients with Hodgkin's disease who have failed conventional therapies. In addition, this approach may aid in cytoreduction prior to bone marrow transplant in patients with superficially located bulky recurrent disease. Hyperthermia may also be considered in combination with chemotherapeutic agents for palliative treatment of recurrences.

The influence of initial hemoglobin and blood pressure levels on results of radiation therapy for carcinoma of the prostate.

A group of 914 patients with carcinoma of the prostate treated by definitive radiotherapy at Stanford between 1956 and 1985 was studied. Of these, the initial hemoglobin level was recorded in 656 cases and the initial blood pressure in 760 cases. End-points studied in actuarial analyses were survival, disease-specific survival, local control, freedom from distant relapse, and occurrence of late intestinal complications. Although the anemic group (Hb less than 13.5 g/dl) was correlated negatively with survival (p = 0.02), there was no correlation with disease-specific survival or local control. The conclusion was that anemia per se did not affect the outcome of radiation therapy. A pulse pressure greater than or equal to 60 mm Hg was significantly correlated with worse survival (p = 0.01) and local control (p = 0.04), but no correlation was found between systolic and diastolic blood pressure and the end-points measured. Neither anemia nor hypertension were significantly correlated with late intestinal complications.