Cervical cancer was treated with a combination of external beam and intracavitary radiation during a 10-year period at Wayne State University. Data were collected for 216 patients treated radically with external beam radiation (EBRT) and low-dose-rate brachytherapy for cervical cancer between 1980 and 1991 at Wayne State University. Patient distribution by stage was IB, 20.8%; IIA, 7.4%; IIB, 26.9%; IIIA, 1.8%; IIIB, 40.7%; and IVA, 2.3 %. Survival curves were constructed using Kaplan-Meier methods and differences between groups were tested for significance using the log-rank test. Multivariate analysis was done using the Cox proportional hazards model. With a median follow-up of 114 months, actuarial disease-free survival for all patients was 60% at 5 years and 55% at 10 years. Actuarial 5-year survival for Stage IB was 79%; for Stage II, 59%; and for Stage III, 53%. There were 14/216 (6%) of patients with severe late complications. On univariate analysis, race was found to be statistically significant, with Caucasian patients having better survival than African American (P = 0.03). The survival for patients treated in shorter overall times was significantly higher (P<0.001), especially with treatment completion in under 58 days. The stepwise Cox multivariate analysis provided the following significant results: race (African American vs. Caucasian; P = 0.04, RR = 1.6), Stage (II vs. I, P = 0.004, RR = 2.6), Stage (III vs. I; P = 0.004, RR = 2.5), and overall treatment time (P = 0.006, RR = 1.62). Rates of local control, survival, and complications among women treated with combined external beam and intracavitary radiation for cervix cancer were similar to those of prior retrospective studies.

Purpose: To introduce and clinically validate a preprocessing algorithm that allows clinical images from an electronic portal imaging device (EPID) to be displayed on any computer monitor, without loss of clinical usability. The introduction of such a system frees EPI systems from the constraints of fixed viewing workstations and increases mobility of the images in a department.Methods and Materials: The preprocessing algorithm, together with its variable parameters is introduced. Clinically, the algorithm is tested using an observer study of 316 EPID images of the pelvic region in the framework of treatment of carcinoma of the cervix and endometrium. Both anterior-posterior (AP/PA) and latero-lateral (LAT) images were used. The images scored were taken from six different patients, five of whom were obese, female, and postmenopausal. The result is tentatively compared with results from other groups. The scoring system, based on the number of visible landmarks in the port, is proposed and validated. Validation was performed by having the observer panel score images with artificially induced noise levels. A comparative study was undertaken with a standard automatic window and leveling display technique. Finally, some case studies using different image sites and EPI detectors are presented.Results: The image quality for all images in this study was deemed to be clinically useful (mean score > 1). Most of the images received a score which was second highest (AP/PA landmarks greater than or equal to 6 and LAT landmarks greater than or equal to 5). Obesity, which has been an important factor determining the image quality, was not seen to be a factor here. Compared to standard techniques a highly significant improvement was determined with regard to clinical usefulness. The algorithm performs fast (less than 9 seconds) and needs no additional user interaction in most of the cases. The algorithm works well on both direct detection portal imagers and camera-based imagers whether analog or digital cameras.Conclusions: We have demonstrated that it is possible to preprocess EPIs in such a way that the clinically relevant landmarks are easily detected on a generic computer screen. The algorithm is system-independent and fast. This allows for the encoding of EPIs in more generalized commercial formats so that distribution of images is facilitated. (C) 1999 Elsevier Science Inc.

Purpose: To retrospectively evaluate the outcome and risk factors in patients treated with radiation for endometrial cancer at time of recurrence.Materials and Methods: Three hundred ninety-nine women were treated with radiation therapy for endometrial cancer at KCI/WSU from January 1980 to December 1994. Of these, 26 patients treated primarily with surgery received radiation therapy at the time of recurrence. Median time to recurrence after surgery was 8 months, with all recurrences occurring within 24 months. Twenty-four patients had recurrences in the vaginal cuff, vagina, or pelvis. These patients received external-beam radiation to the pelvis (45.00-50.40 Gy) and periaortic lymph nodes (45.00-50.00 Gy), along with a boost given by external-beam radiation or brachytherapy (16.00-30.00 Gy). Mean follow-up was 15 months (range 1-85 months).Results: The 2-year survival was 50% and median survival was 16 months (survival range 1-85 months). Of 26 patients, 54% (14) failed locally following radiation therapy. Factors indicative of poor survival included histology (sarcoma, poorly differentiated adenocarcinoma), grade, and lymph node positivity. Histological differentiation influenced local control; lymphovascular space invasion was of borderline significance with regard to local control.Conclusion: Local control and survival for surgically treated endometrial cancer patients who receive radiation at the time of recurrence are poor, with the exception of those patients with recurrent disease limited to the vagina. Early detection of recurrence may improve outcome. Pathologic risk factors may identify those patients at risk for extrapelvic recurrence. Alternative treatment modalities need to he developed for this high-risk group of patients. (C) 1998 Elsevier Science Inc.

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 COG 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. (C) 1997 Elsevier Science Inc.

Background: High-dose-rate (HDR) brachytherapy has been the preferred treatment for cervical cancer at Wayne State University since 1987. The outcome of the first 105 patients treated is analyzed. Purpose: To determine clinical efficacy of the HDR modality. Methods: We reviewed 105 patients and evaluated the 88 patients treated for cervical carcinoma with HDR and external beam radiotherapy (EBRT) from August 1987 to December 1992. Patients received initial external radiation to the pelvis (total dose of 19.8 to 39.6 Gy in 11 to 22 fractions), followed by outpatient HDR brachytherapy (3 fractions/week, 386 cGy/fraction to Point A, total of 8 to 12 fractions) and concurrent daily EBRT (1.8 to 2.0 Gy) to lateral parametria. During the HDR period of treatment, step wedge transmission blocks were used to shield central pelvic tissue while treating peripheral pelvic tissues with EBRT. Patient distributions were as follows: 25, IB/IIA; 35, IIB/IIIA; and 28, IIIB/IVA. There were 56 African American and 32 Caucasian patients with mean age of 55 (range 19–89). The median follow-up was 33 months (range 20 to 76 months). Kaplan–Meier analysis was performed. Results: Three-year survival rates were 88%, IB/IIA; 69%, IIB/IIIA; 56%, IIIB/IVA; and 72% overall. Local control was achieved in 71/88 (80%) of patients. Failure site was cervix or within the pelvis in 12 patients, distant metastasis only 17 patients, and combined local and distant in 5 patients. Of the failures, 82% (28/34) died within 2 years. There were 3 grade III/IV complications (3.4%). Conclusion: Results compare favorably with previous LDR experience.

BACKGROUND:This retrospective analysis examines the frequency, distribution, and the pattern of disease progression of bone metastasis in patients treated for cervical cancer and the use and results of palliative intent radiation therapy.METHODS:Charts, films, and other available records were reviewed for the 41 patients with bone metastasis of the 496 patients with invasive cervical cancer treated at the Gershenson Radiation Oncology Center, Detroit, Michigan, from 1980 through 1989.RESULTS:Several patterns of bone metastasis were observed: (1) direct extension into bone from the parametrial extensions of the primary or recurrent pelvic tumor, (2) direct extension into bone from parenchymal metastasis to distant lymph nodes or lung, (3) regional hematogenous metastasis compatible with Batson's venous plexus distribution, and (4) systemic hematogenous metastasis to distant bones. Eighty percent of the patients were irradiated, and of those, 70% experienced pain relief.CONCLUSIONS:Bone metastasis in patients with cervical cancer is an infrequent but significant occurrence with associated severe dysfunction, other signs of local and distant failure, and short life expectancy. Radiation therapy provides moderate palliation for treatable patients.

Neoadjuvant chemotherapy with cisplatin and mitomycin-C was used in the primary treatment of 17 patients with locally advanced cervical cancer (stages Ib-IIIb; tumor diameter greater than 5 cm) prior to definitive local treatment with radical hysterectomy or radiotherapy. Thirteen of the seventeen patients (76.5%) responded to initial chemotherapy, permitting a radical hysterectomy in ten patients. At histologic examination of the surgically resected primary tumor and lymph nodes, complete pathologic responses were found in 2 patients and partial pathologic responses in 8 patients. The median follow-up time is 14.5 months with a median survival for all patients of 52 weeks. All responders are alive. No therapy-related deaths, major complications, or delay in treatment occurred. Neoadjuvant chemotherapy with mitomycin-C and cisplatin is feasible and may be of benefit for patients with locally advanced cervical cancer.

This paper presents early results of a trial of a three-fractions-per-day (TID) regimen that is more convenient to schedule than the Continuous Hyperfractionated Accelerated Radiotherapy (CHART) protocol currently being tested in Europe. The treatment schedule used in the CHART regimen has been modified from 36 fractions of 1.5 Gy TID in 12 days to 72 fractions of 1.1 Gy in 24 treatment days, with all fractions delivered during normal working hours. With no weekend treatments, the entire course of radiotherapy is completed in less than 5 weeks. The doses used were determined using the L-Q model, with correction for incomplete repair between fractions and for accelerated repopulation of cancer cells. Comparison with historical controls shows statistically significant improvements both in CR rates for the primary tumor and in acute toxicity, as measured by reduced treatment interruptions. L-Q model calculations predict that, compared to the highest dose achieved in previous studies without exceeding tolerance, we are able to obtain a 12% increase in bioeffect dose to the primary tumor due to accelerating the treatment. An analysis of the potential tumoricidal effectiveness of this new treatment regimen shows that it should be better than several other accelerated fractionation schedules being tested for all values of Tot. For short Tpot times, the advantage may be as much as one log cell kill, corresponding to a 10–15% potential improvement in local control.

The experience at the Gershenson Radiation Oncology Center of 32 cases of metastases to the eye or orbit from breast cancer are presented with a review of the literature. The 32 patients were referred for radiation therapy in the period of 1980-1991. Eighteen patients had metastasis to the choroid, 2 patients had involvement of other parts of the eye (anterior chamber +/- choroid), and 11 patients had orbital metastasis. In one patient, the diffuse nature of the disease prevents subsite assignment. Ten of the patients with eye metastases also had brain or meningeal metastases (8 patients concurrent with eye metastases). Four of the 32 patients had bilateral choroidal metastases. A complete course of radiation therapy was delivered to 28 patients, one patient was not treated and 3 patients received only partial treatment because of general deterioration due to other widespread metastases from breast cancer. Of 21 evaluable patients, 15 had definite improvement. There was no progression of the eye metastases in the other 6 patients. The rest (7 patients) were lost to detailed follow-up of the response of the eye metastases. Four patients are still alive without any severe long-term side-effects. The diagnosis, treatment and outcome is presented with a review of the literature. The importance of emergency treatment for rapidly progressing lesions is stressed as well as the need for detailed treatment planning, careful delivery of daily treatments with a high degree of reproducibility and precision to prevent possible damage to sensitive normal structures.

Wayne State University was the site of one of the initial experiences with combination chemotherapy, radiation, and surgery for carcinoma of the thoracic esophagus. This review analyzes all the patients seen with thoracic esophageal carcinoma from 1980 to 1984 inclusive, plus an additional 22 patient pilot study. The great majority of patients seen were treated with combination radiation and chemotherapy, which may have a greater applicability than dose esophagectomy. Eighty-nine patients completed planned preoperative treatment consisting of (5-FU cisplatin and radiation therapy). Of these patients, 39 patients refused or were not offered surgery, and 4 patients are still alive and well several years from treatment initiation. Fifty patients underwent esophagectomy. Twelve of this patients were free of tumor at esophagectomy, and 4 of these are still alive and well several years from treatment. One patient with residual tumor in the esophagectomy specimen alone is still alive. Because of disappointing results and surgical mortality risk, 22 patients were entered on the pilot study, increasing the tumor dose of 5,000 cGy, and increasing chemotherapy to 4 courses. Six patients are still alive in this small series. Since the results of radiation and chemotherapy combination approximates that of best prior trials of radiation therapy alone, a randomized study has been initiated comparing these treatment plans to determine if the combination of radiation and chemotherapy is superior to radiation alone.

Surgical extirpation of the primary tumor with its regional draining lymphatics is the primary treatment of colorectal carcinoma. The outlines of standard therapy are established but particulars have not been defined, especially regarding the issue of adequate clear margins in rectal lesions and the efficacy of extended lymphatic resections. As earlier disease is discovered, the execution of well-designed prospective studies evaluating rectum-sparing operations will be required to settle these issues.