Dose-volume histogram analysis of high dose rate intracavitary brachytherapy for uterine cervix cancer

PURPOSE: We retrospectively analyzed the relationship between dose distribution and local control using a dose-volume histogram (DVH) in patients with cancer of the uterine cervix treated by definitive radiotherapy including intracavitary brachytherapy. METHODS AND MATERIALS: Twenty-five patients with squamous cell carcinoma of the uterine cervix who underwent definitive radiotherapy between August 1987 and April 1994 were selected for the present study. They included 15 patients with local control and 10 patients with local recurrence. In principle, these patients were treated with 50 Gy of external beam pelvic radiotherapy and a point A dose of 24 Gy, in four fractions, of intracavitary brachytherapy. The DVHs of tumor volumes were calculated by superimposing three-dimensional (3D) dose distributions on computed tomography (CT) images taken before brachytherapy. RESULTS: Differential DVHs revealed a tendency for the portion of the total tumor volume to which the delivered dose was low to be larger in patients with local recurrence. The tumor volumes and the absolute dose volumes of which the absorbed dose was less than 24 Gy [DV (< 24 Gy)] were significantly larger in patients with local recurrence than those in local control patients (p = 0.02 and 0.03, respectively). The percent DV (<24 Gy) was not significantly different in the two groups. In patients with larger tumor volume, the absolute DV (<24 Gy) was also larger and a strong linear correlation was noted between them. CONCLUSIONS: The analysis of dose distribution of brachytherapy using DVH was useful to evaluate the quality of dose distribution quantitatively. The absolute dose volume was considered more important than the percent dose volume for evaluation of the clinical outcome. Our study suggested that unfavorable dose distribution for the tumor volume in brachytherapy was one of the reasons of poor local control in patients with large tumor volume.     

Zamifenacin (UK-76, 654) a potent gut M3 selective muscarinic antagonist, reduces colonic motor activity in patients with irritable bowel syndrome

PURPOSE: Retrospective studies suggest that prolonged treatment time adversely affects control rates of squamous carcinomas managed by radiotherapy. From 1989 to 1994 a prospective clinical trial was conducted to assess the feasibility and efficacy of concomitant boost accelerated superfractionated (CBASF) radiotherapy for advanced uterine cervical carcinoma. METHODS AND MATERIALS: Twenty newly diagnosed patients with FIGO stage III squamous cell carcinoma of the cervix were irradiated using a CBASF regimen. Patients received 45 Gy administered to the whole pelvis in 25 fractions in 5 weeks. On Monday, Wednesday, and Friday of the last 3 weeks, an additional 1.6 Gy boost was given 6 hours after the whole pelvis treatment. The 9 boost treatments, totaling 14.4 Gy, were given via lateral fields encompassing the parametria and primary tumor for a cumulative tumor dose of 59.4 Gy. A single low-dose rate brachytherapy procedure was performed within 1 week after the external beam radiotherapy to raise the point A dose to 85-90 Gy in 42 days. Primary endpoints of analysis were local control, complications, and patterns of failure. Results are compared with the outcomes of 21 patients treated with conventionally fractionated (CF) radiotherapy during the same years. RESULTS: Median total treatment time was 46 days in the CBASF group (range 37-62). Median follow-up interval among surviving CBASF patients is 3.8 years. The four-year actuarial local control rates are 78% and 70% in the CBASF and CF groups, respectively (p = ns). Only 2 CBASF patients required a treatment break because of acute toxicity, but severe late complications occurred in 8/20 CBASF patients for a crude rate of 40%. Distant failure was more common than local failure in the CBASF group, and para-aortic node failure occurred in six of the eight CBASF patients with distant failure. CONCLUSIONS: In the management of stage III cervix cancer, the CBASF regimen produced a trend toward improved local control when compared with the CF regimen, shifting the patterns of failure toward a higher rate of isolated distant failures. The high frequency of para-aortic node failure warrants consideration of elective treatment to this region in stage III patients treated with curative intent. Although the high local control rate of the CBASF regimen supports further investigation of accelerated treatment regimens for locally advanced cervix cancer, the unacceptable risk of late complications necessitates refinement in technique and scheduling to improve the therapeutic ratio.     

Results of postoperative radiotherapy of cervix carcinoma after radical versus non radical hysterectomy

We studied the outcome of our 68 cervix carcinoma patients treated either with: 1) radical surgery and postoperative 192Ir high-dose rate afterloading brachytherapy or postoperative radiotherapy to the whole pelvis or with 2) standard hysterectomy and postoperative radiotherapy to the whole pelvis. Forty-eight women were treated by radical hysterectomy from 1988 to 1992 and--due to risk factors--by postoperative radiotherapy (Group 1), 20 other patients (Group 2) pretreated with standard hysterectomy were admitted to the university hospital for postoperative radiotherapy of the whole pelvis. Postoperative radiotherapy consisted of 39.6 Gy total dose using the box technique, plus two afterloading applications with a single dose of 7.5 Gy and 6 Gy external beam therapy to the pelvic lymph nodes sparing the midline. Comparing the Kaplan-Meier plots of both groups, the tumor related survival curve, the locoregional control and the rates of metastatic disease were nearly identical. But in the analysis of special subgroups, patients with positive lymph nodes after standard hysterectomy and postoperative radiotherapy had a worse prognosis (75% three years' survival rate) than patients after radical surgery (86% three years' survival rate). Lymphangiosis was a negative prognostic factor for the patients pretreated with standard hysterectomy (60% versus 80% three years' survival rate), but not for patients after radical surgery (80% three years' survival rate), despite the same radiotherapy in both groups. CONCLUSION: Standard hysterectomy fails to be an adequate treatment for early cervix carcinoma because moderately dosed postoperative radiotherapy cannot achieve complete locoregional control in all cases of positive lymph nodes or invasion of lymph vessels. However, based on the empirical results of many authors and our own results, postoperative radiotherapy is further indicated in high risk cases of cervix carcinoma after radical surgery.     

Clinical stage IE primary lymphoma of the nasal cavity: radiation therapy and chemotherapy

PURPOSE: To determine the appropriate radiation therapy and chemotherapy for primary lymphoma of the nasal cavity to improve the local control and survival rates. MATERIALS AND METHODS: Of the 25 adult patients with stage IE nasal lymphoma, nine underwent local radiation therapy alone and 16 underwent radiation therapy and chemotherapy (intravenous infusion). Radiation doses to the involved area were 22-54 Gy (median dose, 49 Gy). RESULTS: The 5- and 10-year cause-specific survival rates were 91% and 73%, respectively. The 5- and 10-year disease-free survival rates were 83% and 59%, respectively. Eight patients developed recurrent disease: six at the local site, one in the cervical nodes, and one in the small intestine. Five of the six patients with local recurrence received less than 50 Gy. Four of the six patients developed recurrent disease in the treated area; the other two patients developed marginal recurrences. Prognostic factors such as age, sex, maximum tumor size, and lactate dehydrogenase level were of limited value. CONCLUSION: The most common recurrence site was the local site. To improve the local control rate, the involved area should be treated with high-dose radiation therapy. The clinical results did not demonstrate the usefulness of combination chemotherapy for stage IE nasal lymphoma.     

Extraordinary features in the Chlamydomonas reinhardtii chloroplast genome: (1). rps2 as part of a large open reading frame; (2). A C. reinhardtii specific repeat sequence

PURPOSE: To evaluate the clinical efficacy of local vaginal lidocaine application for pain relief during high-dose-rate (HDR) intracavitary brachytherapy for patients with cervical cancer, and to investigate sequential changes in serum levels of lidocaine during the procedures. METHODS AND MATERIALS: This prospective study was designed to examine the analgesic effect, physical response, and side effects of local anesthesia during HDR intracavitary brachytherapy. Forty patients were enrolled. All patients received 10-15 MV X-rays to the pelvis with a total dose of 45-59.4 Gy 5-6 weeks before undergoing HDR intracavitary brachytherapy. All patients underwent first intracavitary brachytherapy under general anesthesia. These patients were randomly allocated to receive one of two different treatment protocols as follows: (1) treatment session - control session - treatment session - control session; or (2) control session - treatment session- control session - treatment session. In the treatment sessions, topical anesthesia was administered using 4 ml of 10% lidocaine solution sprayed liberally on the cervix and vagina during intracavitary brachytherapy. In the control sessions, a placebo was administered in the same manner during brachytherapy. The Hensche's applicators for brachytherapy were inserted into the cervix and vagina 5 min after lidocaine application. The visual analogue scale (VAS) was used to assess pain and discomfort during brachytherapy. Blood pressure and heart rates were measured to evaluate the physiological response. Another prospective study was then performed to investigate the sequential changes of serum lidocaine levels during the anesthetic procedure. Eleven additional patients with similar disease state and demographic characteristics were enrolled and blood samples were obtained before, and 5, 15, 30, and 45 min after the initiation of lidocaine application. RESULTS: The mean VAS values recorded during the treatment sessions and control sessions were 49.9 +/- 24.1 versus 60.1 +/- 24.8, respectively. The value of VAS in the treatment session was significantly lower than that of the control session (p < 0.001). No statistically significant differences were found in the changes of blood pressure and heart rate and in the incidence of side effects during these two types of sessions (p > 0.05). In the drug-level study, serum levels of lidocaine reached a peak 5 min after the initiation of local anesthesia. The mean peak concentrations (Cmax) of lidocaine were 0.50 +/- 0.45 microg/ml. CONCLUSION: Local vaginal anesthesia with 10% lidocaine solution can significantly decrease the degree of painful sensation during HDR intracavitary brachytherapy, and is safe to administer for the procedure for cervical cancer.     

Value of MRI, CT and findings in staging of gynecologic malignancies

PURPOSE: The present study was designed to compare the value of MRI, CT and clinical examination in local tumor staging of gynaecologic malignancies. PATIENTS AND METHODS: 99 patients with clinically suspected carcinoma of the cervix uteri, ovarian carcinoma or tumor recurrence after gynaecologic cancer underwent all three staging modalities. Furthermore CT and MRI were compared in detecting lymph node metastasis and peritoneal implants. RESULTS: MRI was superior to CT and clinical staging in local tumor staging with an accuracy of 77% for cervical carcinoma and of 88% for recurrent tumors, whereas CT achieved an accuracy of 65% and 55% and clinical staging 60% and 63% accuracy for carcinoma of the cervix and recurrent cancer. Especially for local staging of these two tumor entities MRI is very useful. MRI and CT reached comparable results in the detection of ovarian tumors with an accuracy of 73% for MRI and 69% for CI. Both imaging modalities also showed equal results in the detection of lymph node metastasis, so that primary the cost saving use of CT tumor staging for ovarian lesions and lymph node metastasis should be favoured.     

Significance of computed tomography-measured volume in the prognosis of cervical carcinoma

BACKGROUND: Computed tomography (CT) can visualize the volume and shapes of the deep-seated tumors and is expected to predict the treatment outcome in a more quantitative manner. This study was undertaken to learn the prognostic significance of CT-provided information in the radiation therapy of carcinoma of the cervix. METHODS: One hundred thirty-one CT evaluations were systematically applied to 87 patients having carcinoma of the cervix uteri. The cervical mass volume was measured by CT at a certain phase or phases of treatment and was analyzed in relation to their local control at 3 years and the survival at 5 years. RESULTS: The initial volume, measured at the beginning of radiation therapy, was not a significant prognostic guide for the local control. However, the second volume, the volume of cervical lesion measured immediately after the completion of external irradiation, proved to be a prominent prognostic factor for both the 3-year local control and 5-year survival, regardless of the clinical stage. In 52 patients whose second volume was less than 38 cm3, 47 patients (90.4%) were locally controlled for 3 years or more after radiation therapy, whereas 17 of 23 patients (73.9%) whose second volume exceeded 38 cm3 failed in the local control. Five-year actuarial survival rate was 53.1% plus or minus 6.2% in the former group and 26.1% plus or minus 9.6% in the latter group. CONCLUSIONS: CT-aided volumetry provides for an early prediction of treatment failure in radiation therapy for cervical carcinoma.     

125I plaque therapy for uveal melanoma. Analysis of the impact of time and dose factors on local control

BACKGROUND: 125I episcleral plaque therapy has gained wide acceptance for the treatment of uveal melanoma because of its potential to preserve vision, salvage the globe, and provide good local control. A rigorous analysis of the optimum radiation dose, dose rate, and overall treatment time has not been reported with this technique. METHODS: One hundred fifty patients with uveal melanoma treated with 125I plaques between 1982 and 1990 and included in the uveal melanoma study (UMS) database of the Wills Eye Hospital were analyzed. Mean patient age was 60.7 years (range: 17.7-84.6 years). Initial mean tumor size was 9.7 x 8.5 x 3.7 mm with a range of 4.5 to 21.5 mm in basal dimension and 1.2 to 11.8 mm in height. Mean dose to the tumor apex was 94.77 gray (Gy) (29.5-141 Gy). Mean dose rate to the tumor apex was 92.9 cGy/hr (10-292 cGy/hr); the mean dose to the base was 359 Gy (181-692 Gy); the mean dose rate to the base was 348 cGy/hr (112-893 cGy/hr); and mean duration of treatment was 124.7 hours (range: 28-333 hours) RESULTS: With a median follow-up of 68 months, there have been 33 local failures. Mean time to local failure was 19 months (range: 6-78 months). Actuarial local control is 81% at 5 years. Multivariate analysis demonstrates significant correlation of local failure with larger tumor dimension (P = 0.0046), close proximity to the optic disc (P = 0.0029), lower radiation dose to the tumor apex (P = 0.03), lower radiation dose rate to the tumor apex and base (P = 0.01 and 0.03), and longer overall treatment time (P = < 0.0001). CONCLUSIONS: This retrospective analysis reinforces the importance of dose rate, minimum tumor dose, overall treatment time, maximum tumor basal dimension, and proximity to the optic nerve in the treatment of uveal melanoma.     

三维适形放疗配合腔内后装治疗宫颈癌的临床研究

Objective: The aim of our study was to evaluate the outcome and complications of cervical cancer patients undergoing conventional intracavitary brachytherapy (ICBT) treated with 3D-conformal radiotherapy (3DCRT). Methods: Sixty cervical cancer patients were divided randomly into the conformal group and the conventional group. Thirty patients treated with 3D-conformal radiotherapy in the 3DCRT group, when the whole pelvic received DT 40 Gy, a planning CT scan of each patient was obtained and the second 3DCRT therapy plan was taken. Then, continued to irradiate to 50 Gy. At last, 3DCRT was boosted at local involved volumes to the total close of 60 Gy. When 3DCRT was combined with intracavitary brachytherapy, the dose of brachytherapy to point A was 30 Gy/5 fractions. In the conventional group, after a total tumor dose of 40 Gy was delivered by the whole pelvic irradiation, the four-field technique was used to irradiate the total pelvic and regional nodes (median close of 10 Gy), and the involved volumes were boosted to 60 Gy and the dose of brachytherapy to point A was 30 Gy-36 Gy/5-6 fractions. Moreover, both groups were combined with intracavitary brachytherapy respectively. Results: The 1, 2, 3-year survival rates for the 3DCRT group and the conventional group were 96.7%, 93.3%, 90.0% and 86.6%, 76.7%,70% respectively (P = 0.04, P = 0.02 and P = 0.02). There was a statistically significant difference between the two groups.Compared to the two groups each other in toxic effects, except for the Ⅰ-Ⅱ grade rectal and bladder reaction and pelvic fibrosis which was lower in the 3DCRT group (P = 0. 007, P = 0. 006 and P = 0. 015), the side effects were similar and well tolerated in two groups. Conclusion: The all-course 3DCRT combined with intracavitary brachytherapy can be considered as an effective and feasible approach to cervical cancer and may significantly improve the survival rate and reduce the late toxicity. This new rote for 3DCRT merits need further evaluation with large patient numbers and longer follows up.     

Trends in surgical management of astrocytomas and other brain gliomas

PURPOSE: Retrospective analysis of the influence of clinical and technical factors on local control and survival after radiosurgery for brain metastasis. PATIENTS AND METHODS: From January 1994 to December 1996, 42 patients presenting with 71 metastases underwent radiosurgery for brain metastasis. The median age was 56 years and the median Karnofsky index 80. Primary sites included: lung (20 patients), kidney (seven), breast (five), colon (two), melanoma (three), osteosarcoma (one) and it was unknown for three patients. Seventeen patients had extracranial metastasis. Twenty-four patients were treated at recurrence which occurred after whole brain irradiation (12 patients), surgical excision (four) or after both treatments (eight). Thirty-six sessions of radiosurgery have been realized for one metastasis and 13 for two, three or four lesions. The median metastasis diameter was 21 mm and the median volume 1.7 cm3. The median peripheral dose to the lesion was 14 Gy, and the median dose at the isocenter 20 Gy. RESULTS: Sixty-five metastases were evaluable for response analysis. The overall local control rate was 82% and the 1-year actuarial rate was 72%. In univariate analysis, theoretical radioresistance (P = 0.001), diameter less than 3 cm (P = 0.039) and initial treatment with radiosurgery (P = 0.041) were significantly associated with increased local control. Only the first two factors remained significant in multivariate analysis. No prognostic factor of overall survival was identified. The median survival was 12 months. Six patients had a symptomatic oedema (RTOG grade 2), only one of which requiring a surgical excision. CONCLUSION: In conclusion, 14 Gy delivered at the periphery of metastasis seems to be a sufficient dose to control most brain metastases, with a minimal toxicity. Better results were obtained for lesions initially treated with radiosurgery, theoretically radioresistant and with a diameter less than 3 cm.     

Treatment of hemangioblastomas in von Hippel-Lindau disease with linear accelerator-based radiosurgery

OBJECTIVE: Stereotactic radiosurgery is increasingly being used to treat hemangioblastomas, particularly those that are in surgically inaccessible locations or that are multiple, as is common in von Hippel-Lindau disease. The purpose of this study was to retrospectively evaluate the effectiveness of radiosurgery in the treatment of hemangioblastomas. METHODS: From 1989 to 1996, 29 hemangioblastomas in 13 patients with von Hippel-Lindau disease were treated with linear accelerator-based radiosurgery. The mean patient age was 40 years (range, 31-57 yr). The radiation dose to the tumor periphery averaged 23.2 Gy (range, 18-40 Gy). The mean tumor volume was 1.6 cm3 (range, 0.07-65.4 cm3). Tumor response was evaluated in serial, contrast-enhanced, computed tomographic and magnetic resonance imaging scans. The mean follow-up period was 43 months (range, 11-84 mo). RESULTS: Only one (3%) of the treated hemangioblastomas progressed. Five tumors (17%) disappeared, 16 (55%) regressed, and 7 (24%) remained unchanged in size. Five of nine patients with symptoms referable to treated hemangioblastomas experienced symptomatic improvement. During the follow-up period, one patient died as a result of progression of untreated hemangioblastomas in the cervical spine. Three patients developed radiation necrosis, two of whom were symptomatic. CONCLUSION: Although follow-up monitoring is limited, stereotactic radiosurgery provides a high likelihood of local control of hemangioblastomas and is an attractive alternative to multiple surgical procedures for patients with von Hippel-Lindau disease.     

Preoperative criteria for identifying eloquent brain. Intracarotid amytal for language and memory testing

Purpose: to analyze the effect of overall treatment time of radiotherapy on survival and local control in locally advanced prostatic cancer in a split-course treatment setting. Methods and Materials: 168 patients with Stage C prostatic cancer treated during 1979-1989 by the split-course method where the overall treatment time is protracted. Treatment consisted of whole pelvis irradiation of 40 Gy in 4 weeks, followed by a planned 3-week interruption and an additional 26 Gy by the reduced field technique to a total dose of 66 Gy in 9 weeks and 30-33 fractions. The overall treatment time varied from 55 to 100 days. Thirty-eight percent (63) of the patients were treated primarily with radiotherapy, while the rest (105) had received androgen ablative therapy during 2 to 4.5 years before radiotherapy. To examine the effect of treatment time on local control, the patients were divided into three groups ( < or = 63 days, 64-70 days, and > 70 days) by treatment time. Results: the 5-year actuarial survival rates, calculated from the date of diagnosis, were 91% for the hormonally manipulated patients and 69% for the patients treated with radiotherapy alone. The 5-year actuarial local control rates, counted from the start of radiotherapy, were 84% for radiotherapy and 80% for the hormonally manipulated group. Overall, no significant effect of treatment time could be seen, either for radiotherapy alone or for the hormonally manipulated group. The results were similar when the material was further divided by T category and histologic grade. Conclusions: no significant effect of overall treatment time (55 to 100 days) on survival or local control was found in either group. The survival time from diagnosis was longer in the hormonally pretreated group. Apparently, with adequate doses ( > or = 65 Gy) the overall treatment time becomes less important for local control of advanced prostatic cancer, even in a split-course treatment setting.     

Combined treatment of inoperable carcinomas of the uterine cervix with radiotherapy and regional hyperthermia. Results of a phase II trial

AIM: The disappointing results for inoperable, advanced tumors of the uterine cervix after conventional radiotherapy alone necessitates improving of radiation therapy. Simultaneous chemotherapy or altered radiation fractionation, such as accelerated regimen, increase acute toxicity and treatment is often difficult to deliver in the planned manner. The purpose of this phase II study was to investigate the toxicity and effectiveness of a combined approach with radiotherapy and regional hyperthermia. PATIENTS AND METHODS: From January 1994 to October 1995 18 patients with advanced carcinomas of the uterine cervix were treated in combination with radiotherapy and hyperthermia. The patients were treated with 6 to 20 MV photons delivered by a linear accelerator in a 4-field-box technique to a total dose of 50.4 Gy in 28 fractions. In the first and fourth week 2 regional hyperthermia treatments were each applied with the Sigma-60 applicator from a BSD-2000 unit. After this a boost to the primary tumor was given with high-dose-rate iridium-192 brachytherapy by an afterloading technique with 4 x 5 Gy at point A to a total of 20 Gy and for the involved parametrium anterioposterior-posterioanterior to 9 Gy in 5 fractions. RESULTS: The acute toxicity was low and similar to an external radiotherapy alone treatment. No Grade III/IV acute toxicity was found. The median age was 47 years (range 34 to 67 years). In 16 of 18 patients a rapid tumor regression was observed during combined thermo-radiotherapy, which allowed the use of intracavitary high-dose-rate brachytherapy in these cases. Complete and partial remission were observed in 13 and 4 cases, respectively. One patient did not respond to the treatment. The median follow-up was 24 months (range 17 to 36 months). The local tumor control rate was 48% at 2 years. Median T20, T50 and T90 values were 41.7 degrees C (range 40.3 to 43.2 degrees C), 41.1 degrees C (range 39.2 to 42.5 degrees C) and 39.9 degrees C (range 37.7 to 41.9 degrees C), respectively. Cumulative minutes of T90 > 40 degrees C (Cum40T90) and cumulative minutes, which were isoeffective to 43 degrees C, were calculated (CEM43T90, CEM43T50, CEM43T20). CEM43T90 was found to be a significant parameter in terms of local tumor control for the 4 hyperthermia treatments (p = 0.019). CONCLUSIONS: This treatment modality has proved to be feasible and well tolerable. The rapid tumor shrinkage in the combined approach of radiotherapy with hyperthermia before beginning brachytherapy seems to be a good prerequisite for improving of the disappointing results in cure of advanced cancer of the uterine cervix.     

Chronic lymphocytic leukemia presenting as pyogenic arthritis of the proximal interphalangeal joint

PURPOSE: To evaluate the results of 125I brachytherapy in colorectal cancers recurrent in the pelvis and paraortics. METHODS AND MATERIALS: From September 1989 to January 1997, 29 patients with colorectal adenocarcinoma recurrent in the pelvis or the paraortic nodes were treated intraoperatively with permanent 125iodine seed implantation at the James Cancer Center of The Ohio State University (OSU). All patients had undergone prior surgery; 72% had prior EBRT. The implanted residual tumor volume was microscopic in 38% and gross in 62%. The implanted area (median 25 cc) received a median minimal peripheral dose of 140 Gy to total decay. An omental pedicle was used to minimize irradiation of the bowel. Five patients received additional postimplant EBRT (20-50 Gy; median 30 Gy). RESULTS: The 1-, 2-, and 4-year actuarial local-regional control rates were 38%, 17%, and 17%, respectively, with a median time to local failure of 11 months (95% CI 10-12 months). The first manifestation of disease progression in 52 % of the patients was local-regional. In addition, 22 patients (75%) developed distant metastases. The 1-, 2-, and 4-year actuarial overall survival rates were 70%, 35%, and 21%, (median = 18 months; 95% CI: 14-22 months). Overall survival was better for patients smaller volume implants (p = 0.007), with a lower total activity implanted (p = 0.0003), with a smaller number of implanted sites (p = 0.004), and with microscopic residual disease (p = 0.01). Patients receiving additional EBRT also had a better prognosis (p = 0.005). Local tumor progression was the cause of death in 34% of the patients who have died at the time of this report and 56% died of distant metastases. Of the patients, 13 (45%) experienced 15 toxic events, including 3 patients (10%) with enteric fistula. Neuropathy was not observed. CONCLUSIONS: 125I brachytherapy can be successfully used for salvage in patients with recurrent colorectal cancer. Patients with isolated, microscopic, or minimal gross residual disease requiring small-volume implants and those receiving additional EBRT have a better prognosis. Postimplant EBRT is now routinely added, even for previously irradiated patients, in an attempt to improve local control. Compared to IOERT and IOHDR, 125I brachytherapy is not associated with clinical neuropathy, probably due to the continuous low dose rate irradiation delivered by the 125I seeds.     

Intraoperative brachytherapy, laryngopharyngoesophagectomy, and gastric transposition for patients with recurrent hypopharyngeal and cervical esophageal carcinoma

OBJECTIVE: To evaluate the role of laryngopharyngoesophagectomy (LPE), intraoperative 125I brachytherapy (IOBT), and gastric transposition (GT) in patients with recurrent carcinoma involving the hypopharynx, or cervical esophagus. METHODS: Between 1988 and 1994 a total of 21 patients were managed with LPE/IOBT/GT. All patients had documentation of recurrent disease at the hypopharynx or cervical esophagus and had previously been treated with external-beam radiation (EBRT) to a total median dose of 60 Gy. Median age was 67 years, with 17 male patients and four female. IOBT was performed in all cases with permanent 125I implantation. Medical records were retrospectively reviewed. Overall survival, local control, and complications were evaluated. Median follow-up was 6 months. RESULTS: The median activity of 125I was 36 mCi, with a median dose of 80 Gy to the region at risk. Fifteen patients had lymph node dissections performed in conjunction with LPE, and 10 patients had nodal involvement on pathologic examination. Margins were microscopically positive in nine patients, and lymphvascular space invasion noted in 13. Actuarial survival at 1 and 3 years was 32% and 14%, respectively, with patients alive and with local control at 6, 24, 36, and 48 months (negative margins). Actuarial local control at 1 and 3 years was 63%. Complications included fistula in five patients, facial edema in four, protracted facial pain in two, cervical abscess in one, and mucosal hemorrhage in one. CONCLUSION: Patients with recurrent carcinoma of the hypopharynx or cervical esophagus after EBRT have an extremely poor prognosis. LPE, IOBT, and GT may provide very good local control for all candidates and prolonged survival for a small percentage of patients with an acceptable risk profile.     

Results of high-dose thoracic irradiation incorporating beam's eye view display in non-small cell lung cancer: a retrospective multivariate analysis

PURPOSE: To review the University of Michigan clinical experience in nonsmall cell lung cancer using high-dose thoracic irradiation (> or = 60 Gy) so that a starting dose for our prospective dose-escalation study could be determined. METHODS AND MATERIALS: Eighty-eight consecutive patients diagnosed with medically inoperable or locally advanced, unresectable nonsmall cell lung cancer were identified who were treated with thoracic irradiation alone to a minimum total dose of 60 Gy (uncorrected for lung density). All patients except four (95%) underwent computed tomography scanning for treatment planning that included beam's eye view display for tumor and critical structure localization. All patients were treated with standard fractionation in a continuous course to uncorrected total doses ranging from 60 to 74 Gy (median, 67.6 Gy). RESULTS: The median follow-up exceeds 24 months for all surviving patients (range, 12 to 78 months). The median survival time was 15 months, and the 2- and 3-year overall actuarial survival rates were 37% and 15%, respectively. Survival was significantly different between stage of disease (p = .004) and N-stage (p = .002) by univariate analysis. In a multivariate analysis, stage becomes the only characteristic significantly associated with outcome. The median time to local progression for 86 evaluable patients was 29 months. Stage (p = .0003), T-stage (p = .0095) and N-stage (p = .027) were significantly different with respect to local progression-free survival by univariate analysis. However, only stage was prognostic for local progression-free survival by multivariate analysis. There was no difference between large volume treatment (inclusion of the contralateral hilar and supraclavicular lymph nodes) and small volume treatment (exclusion of these elective nodal sites) with respect to local progression-free survival (p = .507) or survival (p = .520). With regard to dose, there was no significant difference between patients who received > 67.6 Gy and patients who received < or = 67.6 Gy with respect to local progression-free survival (p = .094) or survival (p = .142). Within the Stage III subgroup, local progression-free survival (p = .018) and survival (p = .061) were longer favoring the high-dose group of patients. Despite these doses, disease progression within the irradiated field was the predominant first site of treatment failure. CONCLUSION: This retrospective study has shown that it is feasible to deliver uncorrected tumor doses as high as 70 Gy using standard fractionation in NSCLC with acceptable morbidity. Local control remains a significant problem. These data indicate justification for a starting dose in a prospective radiation dose-escalation study.     

Postoperative radiation for cervical cancer with pathologic risk factors

PURPOSE: To examine the efficacy of postoperative radiation therapy for early-stage cervical cancer with pathologic risk factors. METHODS AND MATERIALS: We reviewed the charts of 83 patients who received postoperative radiation therapy at our facility from March 1980 to November 1993 for early stage cervix cancer with positive surgical margins, positive pelvic or periaortic lymph nodes, lymphovascular space invasion, deep invasion, or for disease discovered incidently at simple hysterectomy. Twenty-eight patients received low dose rate (LDR) intracavitary radiation with or without external beam pelvic irradiation and 55 patients received external beam pelvic irradiation with high dose rate (HDR) intracavitary implants. Of these 83 patients, 66 were evaluable--20 LDR and 46 HDR patients. All patients received 45-50 Gy external beam irradiation and 20 Gy LDR equivalent intracavitary irradiation prescribed to 0.5 cm below the mucosa. Ninety percent of the LDR group and 92% of the HDR group completed treatment within < 56 days. Treatment-related toxicities were scored according to the GOG toxicity scale. Mean and median follow-up times were 101 months and 111 months (3-172 months) for the LDR group and 42 and 40 months (3-98 months) for the HDR group. RESULTS: The 5-year disease-free survival was 89% for the LDR group and 72% for the HDR group. Local control was observed in 90% (18 out of 20) of the LDR patients and 89% (41 out of 46) of the HDR patients for an overall local control rate of 89.5%. Two of 20 LDR patients (10%) experienced recurrence (two pelvic with distant metastasis). Nine of 46 HDR patients (22%) had recurrence of disease (three pelvic, four distant metastasis, and two pelvic with distant metastasis). In the HDR group, 6 out of 16 (38%) with positive lymph nodes died of disease whereas, 27 out of 30 (90%) of the patients with negative lymph nodes remain free of disease. Three of 20 (15%) LDR patients and 4 out of 46 (9%) HDR patients experienced Grade 2 or 3 late treatment- related complications. No patient in either group had Grade 4 or 5 complications. Pathologic risk factors were analyzed. Lymph node positivity and lymphovascular space invasion were found to be significant (p = 0.01 and p = 0.02). Positive margins, deep invasion, and age were not significant. CONCLUSION: Our results demonstrate the efficacy of postoperative irradiation for cervical cancer with pathologic risk factors. Overall, the local control rate was 89.5% The HDR results demonstrate that this method can be delivered safely and effectively.     

Specificity of the BAX polymerase chain reaction system for detection of the foodborne pathogen Listeria monocytogenes

PURPOSE: The purpose of this study was to evaluate the toxicity and efficacy of twice-daily external irradiation to the pelvis and para-aortics with brachytherapy and concurrent chemotherapy for carcinoma of the cervix with positive para-aortic lymph nodes. METHODS AND MATERIALS: This study was designed to administer twice-daily radiation doses of 1.2 Gy to the pelvis and para-aortics at 4- to 6-h intervals, 5 days per week. The total external radiation doses were 24 to 48 Gy to the whole pelvis, 12 to 36 Gy parametrial boost, and 48 Gy to the para-aortics with an additional boost to a total dose of 54 to 58 Gy to the known metastatic para-aortic site. One or two intracavitary applications were performed to deliver a total minimum dose of 85 Gy to point A. Cisplatin (75 mg/m2, days 1 and 22) and 5-FU (1000 mg/m2/24 h x 4 days; days 1 and 22) were given for two or three cycles. RESULTS: Twenty-nine patients with clinical Stages I to IV carcinoma of the cervix with biopsy-proven para-aortic lymph nodes were enrolled in this study. Hyperfractionated external radiotherapy was completed in 86% (25 of 29). Brachytherapy was given in two applications to 48% (14 of 29), 31% (9 of 29) had one intracavitary application, 14% (4 of 29) had no brachytherapy, one had three applications, and one had five HDR applications. Radiotherapy was completed per protocol in 69%. Three courses of chemotherapy were given to 24% (7 of 29), 72% (21 of 29) received two courses, and one patient did not receive chemotherapy. The acute toxicity from chemotherapy was Grade 1 in 3%, Grade 2 in 17%, Grade 3 in 48%, and Grade 4 in 28%. Radiotherapy toxicity was Grade 1 in 7%, Grade 2 in 34%, Grade 3 in 21%, and Grade 4 in 28%. One Grade 5 toxicity occurred and the patient died from a myocardial infarction from chemotherapy and radiotherapy colitis during her course of therapy. The median follow-up time was 18.9 months. The overall survival estimates were 59% at 1 year and 47% at 2 years. The probability of local-regional failure was 38% at 1 year and 49% at 2 years. The probability of disease failure at any site was 45% at 1 year and 59% at 2 years. CONCLUSION: The results suggest that twice-daily external irradiation to the pelvis and para-aortics with brachytherapy and concurrent chemotherapy resulted in an unacceptably high rate (31%, 9 of 29) of Grade 4 nonhematologic toxicity. One patient died from complications of therapy. Radiotherapy was completed per protocol in 69%. The survival estimates appear no better than standard fractionation radiotherapy without chemotherapy. Additional follow-up is necessary for long-term survival estimates.     

Adjuvant radio-chemotherapy in cancer of the rectum treated with radical surgery and with high risk of recurrence. Preliminary results of a prospective study

INTRODUCTION MATERIAL AND METHODS: From January, 1990, to December, 1995, 138 consecutive patients with radically resected stage II and III rectal and rectosigmoid cancers were treated with adjuvant radiochemotherapy. Eighty-one patients with 24 months' follow-up were assessable. Low anterior resection (LAR) was performed in 64 (79%) patients and abdominoperineal resection (APR) in 17 (21%). Twentynine (36%) stage II and 52 (64%) stage III patients entered the study. Within 45-60 days from surgery all patients received 5-Fluorouracil chemotherapy at the dose of 500 mg/m2/iv/d 1-5, every 4 weeks, for six cycles. Chemotherapy cycles 3 and 4 were administered at the same daily dose on radiotherapy days 1-3 and 29-31. Radiotherapy total dose consisted of 45 Gy/1.8 Gy/day administered in 5 weeks with 18 MV photon beam to the pelvis with the four field "box" technique. Perineal scar was encompassed only after APR. A boost dose of 5.4 Gy to the tumor bed was given in 3 fractions of 1.8 Gy. Median follow-up was 37 months (range: 24-74 months). RESULTS AND DISCUSSION: Overall recurrent disease was reported in 28 of 81 patients (34%): local, systemic and both local and systemic relapses in 9 (11%), 14 (17%) and 5 (6%) cases, respectively. According to local extension, recurrence rates were 10% and 48% in stages II and III, respectively. Five-year overall and disease-free actuarial survivals were 64% and 61%, respectively. Median time to relapse was 15 months (range: 7-43 months). Significant prognostic factors for better tumor control were: stage (II vs III), disease site (proximal vs distal rectum), the surgical procedure (LAR vs APR), the number of involved nodes (< or = 4 vs > 4) and no extracapsular node invasion. The recommended dose of combined radiochemotherapy regimen used in this trial was generally well tolerated. The incidence of any grade > or = 3 acute toxicity (according to WHO grading) was 20% diarrhea, 6% tenesmus and 4% myelosuppression. Five (6%) patients had cronic diarrhea and other 3 (4%) radiotherapy-related severe late toxicity which required surgery. CONCLUSIONS: This study seems to provide similar survival and recurrence notes to other radio-chemotherapy regimens published in the literature. However, a more aggressive approach is warranted in stage III patients considering the low 5-year survival recorded.     

Risk analysis of linear accelerator radiosurgery

PURPOSE: To evaluate the toxicity of stereotactic single-dose irradiation and to compare the own results with already existing risk prediction models. METHODS AND MATERIALS: Computed tomography (CT) or magnetic-resonance (MR) images, and clinical data of 133 consecutive patients treated with linear accelerator radiosurgery were analyzed retrospectively. Using the Cox proportional hazards model the relevance of treatment parameters and dose-volume relationships on the occurrence of radiation-induced tissue changes (edema, localized blood-brain barrier breakdown) were assessed. RESULTS: Sixty-two intraparenchymal lesions (arteriovenous malformation (AVM): 56 patients, meningioma: 6 patients) and 73 skull base tumors were selected for analysis. The median follow-up was 28.1 months (range: 9.0-58.9 months). Radiation-induced tissue changes (32 out of 135, 23.7%) were documented on CT or MR images 3.6-58.7 months after radiosurgery (median time: 17.8 months). The actuarial risk at 2 years for the development of neuroradiological changes was 25.8% for all evaluated patients, 38.4% for intraparenchymal lesions, and 14.6% for skull base tumors. The coefficient: total volume recieving a minimum dose of 10 Gy (VTREAT10) reached statistical significance in a Cox proportional hazards model calculated for all patients, intraparenchymal lesions, and AVMs. In skull base tumors, the volume of normal brain tissue covered by the 10 Gy isodose line (VBRAIN10) was the only significant variable. CONCLUSIONS: These results demonstrate the particular vulnerability of normal brain tissue to single dose irradiation. Optimal conformation of the therapeutic isodose line to the 3D configuration of the target volume may help to reduce side effects.