Analysis of temperature distributions of interstitial hyperthermia using a hot water system.

PURPOSE: Interstitial hyperthermia is being increasingly used as an adjunct to brachytherapy in the treatment of implantable tumors. Of the several interstitial hyperthermia systems available, perhaps the simplest to use are the circulating hot water systems. An analysis of the thermal distributions obtained during our initial experience with interstitial hyperthermia using steel needles and the KHS-9 hot water system was therefore undertaken. METHODS AND MATERIALS: Between September 1988 and June 1991, 23 patients were treated with interstitial Iridium-192 high dose-rate brachytherapy immediately followed by interstitial hot water hyperthermia. A total of 32 implants were performed in these patients, of whom 14 presented with primary anal carcinomas, six with recurrent gynecological tumors, and three with subcutaneous metastases from malignant melanoma. All but the patients with anal cancers had failed in previously irradiated sites. One or two heat treatments were delivered to each tumor with the goal to reach and maintain an intratumoral temperature 42.5 degrees C over a period of 40 min. Temperature measurements were carried out by mapping three-point thermocouple probes along the track of one or two needles parallel to the implanted needles. RESULTS: Minimum intratumoral temperatures exceeded 42.0 degrees C in 41%, 42.5 degrees C in 19%, 43.0 degrees C in 13%, and 44.0 degrees C in 3% of treatments. The average minimum, maximum, and mean intratumoral temperatures for all treatments were 41.7 degrees C, 43.5 degrees C, and 42.6 degrees C, respectively. CONCLUSION: The temperature profiles obtained in this series compare favorable to those reported in literature for radiofrequency local current field systems and suggest the hot water device may be an alternative heating method. It is relatively simple to use, does not require shielding of the treatment room, and can easily be adapted to currently used brachytherapy systems. Further patient accrual and longer follow-up will be needed to assess the clinical results in terms of tumor response and duration of response.

Surgical and non-surgical treatment of cancer of the oesophagus and the oesophagogastric junction: results of 200 consecutive cases.

200 consecutive, unselected patients with cancer of the oesophagus or the oesophagogastric junction (89 squamous, 110 adenocarcinoma or undifferentiated, 1 oat cell) between 1984 and 1987 were reviewed. Resection with postoperative adjuvant irradiation in the cases of squamous cell cancer, was carried out in 51 patients and non-surgical treatment [57 combined dilation and Nd-YAG-laser, 64 iridium 192 high-dose rate brachytherapy with or without 60 Gy external beam irradiation (EBR); 28 endoprostheses] was performed in the remaining 149 patients. The overall 5 year-survival rate was 9.2% (resections: 17.9%, non-resected: 5.2%). Resected nodal negative T1 or T2 patients had the best prognosis (45.8% 5-year survival). The median survival following dilation and laser was 3.4 months for all T-stages. Endoprostheses yielded a median survival of 1.7 months. Intracavitary brachytherapy gave the best palliative result with 6.5 months median survival, whereby only T1 and T2 patients benefitted from additional EBR. Histological subtype, age, sex or tumour localization did not influence survival. Multivariate analysis showed that in M0 patients the choice of treatment had a significant impact on prognosis.

Bladder and rectal dose of gynecologic high-dose-rate implants: comparison of orthogonal radiographic measurements with in vivo and CT-assisted measurements.

Bladder and rectal doses were retrospectively reviewed in 281 patients who underwent implantation of 575 gynecologic iridium-192 high-dose-rate devices. Dose measurements obtained with orthogonal radiography, in vivo thermoluminescent dosimetry, and computed tomography (CT)-assisted planning were compared. Measurements of bladder dose derived from radiographs revealed a significant difference between bladder neck dose and bladder base dose (P less than .0001). In 17% of cases, the dose to the bladder base was at least double the dose to the bladder neck. The mean dose to the rectum calculated from radiographs was 85.9% (cervix) and 90.2% (vaginal vault) of the prescribed fraction dose. The correlation coefficient factor between doses determined with orthogonal radiographs and doses determined with in vivo measurements was .9694. The dose to the bladder neck and to four rectal points determined with corresponding CT images revealed a deviation of 4% and 7%, respectively. However, calculations at the rectal wall cephalic to the specified rectal points showed higher doses to the rectum, with a ratio of 1-1.6. CT-assisted calculations at the bladder base also revealed doses that were higher than those obtained with radiographs alone by a ratio of 1.4-2.2. CT-assisted dosimetry is the method of choice.

Anti-carcinoembryonic antigen immunoscintigraphy (technetium-99m-monoclonal antibody BW 431/26) and serum CEA levels in patients with suspected primary and recurrent colorectal carcinoma.

This study comprises a total of 141 patients with suspected primary and recurrent colorectal carcinomas, in whom immunoscintigraphy with 99mTc-Mab BW 431/26 was performed. Whole-body scans were done 5.5 hr and SPECT imaging of the abdominal region was done at 6 and 24 hr postinjection of 1100 MBq 99mTc-labeled Mab (1 mg). In the course of primary tumor identification (n = 65), sensitivity of anti-CEA immunoscintigraphy was 95%, specificity 91%. In the diagnosis of early recurrences (n = 76), immunoscintigraphy was the method of choice to clarify the problem (sensitivity 94%; specificity 86%). Overall sensitivity of immunoscintigraphy in patients with suspected colorectal carcinomas and early recurrences was 95%, specificity 88%. Human anti-mouse antibodies were found in 29% (80% predominantly anti-isotypic, 20% predominantly anti-idiotypic). In contrast to anti-CEA immunoscintigraphy, the results of serum CEA levels were rather disappointing. Only 18 out of the 43 surgically verified primary colorectal carcinomas and 17 out of 32 patients with recurrences showed elevated serum CEA levels. In our clinical experience with this 99mTc-labeled anti-CEA antibody, immunoscintigraphy can play an important role in the identification of early colorectal recurrences and in postoperative colorectal cancer patients it should be performed in cases with unclear transmission computed tomography.

Consolidation radiotherapy following carboplatin-based chemotherapy in radically operated advanced ovarian cancer. A pilot study.

Adjuvant chemoradiotherapy was administered to 26 patients with stage Ic-IV ovarian cancer after radical cytoreductive surgery. All patients received six cycles of carboplatin, epirubicin, and prednimustine and had no evidence of disease after completion of chemotherapy. They received whole-abdominal radiation and radiation to the retroperitoneal lymph nodes. Five (23%) of the patients were discontinued on this protocol because of myelosuppression, progressive disease, or withdrawal. One patient had a small bowel obstruction due to intraperitoneal adhesions. The survival of 10 Stage III ovarian cancer patients who received chemoradiotherapy and were evaluable for assessment of treatment efficacy was retrospectively compared with the survival of 11 Stage III patients who received chemotherapy only. At 36 months, a slight advantage of the chemoradiotherapy versus the chemotherapy-only group was observed (p = 0.11). These preliminary results suggest that adjuvant chemoradiotherapy may prolong the "no evidence of disease" interval of radically operated ovarian cancer patients. Toxicity is acceptable when second-look surgery is avoided and when subsequent radiotherapy is limited to patients with no clinical evidence of disease.

[Value of magnetic resonance tomography after primary irradiation of carcinoma of the cervix uteri: evaluation of therapeutic success and follow-up]. / Stellenwert der Magnetresonanztomographie beim primär bestrahlten Karzinom der Cervix uteri: Therapieerfolgsbeurteilung und Nachsorge.

This study investigates the reliability of magnet resonance imaging in the evaluation of response to therapy and in follow-up after primary irradiation (RTX) of uterine cervical carcinomas in 25 patients (follow-up eleven to 39 months). Most of the tumors showed six months after RTX a significant reduction of volume and signal intensity in T2 weighted images. 20/25 (80%) showed a total tumor regression, 5/25 (20%) had a residual tumor (all of them had a primary tumor volume higher than 50 ccm). Four patients got a recurrent tumor in follow-up. Residual and recurrent tumors showed like the primary in heavily T2 weighted images significant higher signal intensity than fibrosis. Therefore posttreatment fibrosis is distinguishable from residual or recurrent neoplasm. Early radiation fibrosis (less than 6 months after RTX) showed higher signal intensity than fibrosis in later stages. This fact may be the cause of false positive results in searching for residual tumor within the first six months after RTX. Our results indicate that magnet resonance imaging is a reliable method to evaluate tumor response after radiation treatment and to detect recurrent neoplasm. The results of a greater patient population over a longer period of follow-up will be presented in future.

Total unilateral lung gangrene in Hodgkin's disease: treatment by thoracostomy.

Total gangrene of the left lung developed in a 30-year-old male patient with a pulmonary recurrence of Hodgkin's disease after mediastinal irradiation and chemotherapy. Clinically, tension pyopneumothorax and severe septic shock were present. Surgical repair was done by thoracostomy, resecting three ribs. A 2 x 0.5-cm hole in the necrotic wall of the left main bronchus was covered with an intercostal muscle bundle. The necrotic pleural surfaces were treated openly by daily change of dressings. The patient recovered satisfactorily and underwent four further courses of chemotherapy without any complications.

Radiation therapy in stage III ovarian cancer following surgery and chemotherapy: prognostic factors, patterns of relapse, and toxicity: a preliminary report.

Twenty patients with FIGO stage III epithelial ovarian cancer who had undergone maximum cytoreductive surgery (including pelvic and paraaortic lymph node dissection) and combination chemotherapy (4-10 cycles, median 6) were treated with irradiation to the abdomen and pelvis with 30 Gy followed by diaphragmatic/paraaortic and pelvis boost fields to 42 and 51.6 Gy, respectively. Second-look laparotomy was not performed. Seventeen of 20 patients completed the planned course of radiation. In 2 cases, failure to complete treatment was related to acute hematologic toxicity, and 1 patient refused further treatment. Five patients (29%) required treatment breaks ranging from 8 to 16 days (median, 12 days) due to pancytopenia. Actuarial overall survival and relapse-free survival at 3 years for the 17 patients who completed radiation was 69 and 47%, respectively, with follow-up ranging from 19 to 53 months (median: 24, mean: 27.6 months). Seven patients (41%) relapsed within the abdomen alone and 2 patients developed extraabdominal lymph node metastasis as their sole site of failure. The prognostic factors evaluated for correlation with relapse-free survival included histologic subtype, grade, amount of residual disease at the time of surgery, and nodal involvement; only residual tumor at surgery (none vs less than or equal to 2 cm or greater than 2 cm) was found to be statistically significant (P less than 0.01). Three-year overall survival correlated with amount of residual disease following the initial cytoreductive surgery. It was 100% for patients with no residual disease, 66.7% for less than or equal to 2 cm, and 26.7% for those with greater than 2 cm residual disease, respectively. Radiation treatment was well tolerated, with only one patient developing treatment-related bowel obstruction 7 months after radiation therapy. The results of this planned trimodality treatment approach compare favorably with those reported following surgery and chemotherapy, particularly in patients who have been maximally cytoreduced.

Intraoperative plus external beam irradiation in nonresectable lung cancer: assessment of local response and therapy-related side effects.

Since 1987, 24 patients with inoperable non-small-cell lung cancer (NSCLC), stage T1-3 N0-2 M0, have undergone lymph node dissection and intraoperative radiation therapy (IORT) to the primary with 10-20 Gy. Patient selection criteria were nonresectability based on severe cardiorespiratory impairment, no radiological evidence of distant metastases and a Karnofsky performance status of greater than 80. In 18 patients the IORT procedure was followed by an external beam radiation series (EBR) including the tumor with 46 Gy and the regional lymph nodes with 46/56 Gy. The tumor response was assessed by CAT-scan volumetry before the institution of IORT, 4 weeks later, before the onset of EBR, 8 weeks after the combined treatment course and on a 3 months basis thereafter. Prospectively, MRI of the thorax with/without Gadolinium-DTPA was performed to examine contrast enhancement and signal behavior of the tumor, in an attempt to differentiate residual disease compared to therapy-related collateral damage. So far, 18 patients have completed the combined treatment course with a median follow-up of 11 months (range 4.5 to 25 months). The overall local response rate (CR and PR) was 88.2%. In detail, 11 complete responses, 6 partial responses and one minimal response were observed. The overall and recurrence-free survival at 25 months was 49.6% and 83.3%, respectively.

[MR study of bone marrow changes of the spine following radiotherapy]. / MR-Untersuchung von Knochenmarksveränderungen in der Wirbelsäule nach Strahlentherapie.

MR examinations of bone marrow variations in the spine after radiotherapy were performed on 24 patients in the thoracic and lumbar vertebral column. The actinically affected bone marrow showed a characteristic increase of signal intensity in T1-weighted sequences in the sagittal plane, due to conversion of red marrow to fatty marrow. The dose in the well-defined radiation areas was between 28 and 70 Gray (Gy). The lowest dose, applied to the bone-marrow bordering on the defined radiation areas, where we still could find an increase of signal intensity, was below 2.6 to 5 Gy. MR imaging was performed between 6 and 9 month after radiotherapy.

Intraoperative radiation therapy combined with external irradiation in nonresectable non-small-cell lung cancer: preliminary report.

Twenty-one patients with nonresectable non-small-cell lung cancer (15 squamous-cell, 4 adeno, 2 large-cell; T1-T3, N0-N2, all M0) underwent lymph node dissection and intraoperative irradiation of the tumor (IORT) with doses between 10 and 20 Gy (energies: 7 to 20 MeV electron beam). Postoperatively, 46-56 Gy external beam irradiation (8 or 23 MeV photon beam) were delivered to the mediastinum and 46 Gy to the tumor bearing area. Fifteen patients were available for follow-up investigations. The CT-scan tumor volumetry 4 weeks postoperatively showed a significant overall decrease (Wilcoxon test: p less than 0.05) with eight minor responses (MR) (tumor regressions between 4 and 45%) and six partial responses (PR) (between 50 and 84%). One case was not evaluable. A second volumetry after external irradiation was done in 14 patients, 18 weeks after IORT, showing 3 complete responses, 10 partial responses (62 to 84%), and 1 minor response (28%). The recent volumetries (10 patients) between 4.5 and 16.5 months after IORT showed 7 complete responses and 3 partial responses (63 to 94%). One patient died from intrabronchial hemorrhage at 7 weeks. Three others died from unrelated causes, 6, 12 and 14 months, respectively, after IORT and in one further case the cause of death at 15 months was local tumor regrowth. Within the median time elapsed since IORT (12 months) only this one case of local regrowth and one further case of distant spread were observed.

[Intraoperative radiotherapy (IORT) at the Graz University Clinics: results of a pilot study on non-small cell lung carcinoma]. / Intraoperative Strahlentherapie (IORT) an den Universitätskliniken Graz: Ergebnisse einer Pilotstudie nichtkleinzelliger Lungenkarzinome.

A pilot study was undertaken during which 15 patients with non-small cell pulmonary carcinomas were exposed to an intraoperative irradiation; twelve out of them were submitted to an additional percutaneous photon therapy. The criteria used to select these patients were functional inoperability, exclusion of remote metastases, and a Karnofsky index greater than 70. Central and peripheral tumors of the stages T1-3, N0-2 were included into the study after histological confirmation of the diagnosis. The local regression rate of the primary tumor can be assessed quite well despite the short follow-up time of 4.5 to 16 months (10 months on an average) which does not yet allow to make a conclusion as to a prolongation of the disease-free survival time. Already two months after the end of external irradiation, a complete remission (CR) was seen in three patients (25%), a partial remission (PR) in seven patients (67%), and a minor remission (MR) in one patient. In the course of further follow-up, the number of complete remissions increased to six (50%). We are encouraged by the small morbidity and a therapeutic response higher than average to continue with this therapy method in patients who, for the time being, are still selected according to strict criteria.

[Intraoperative radiotherapy (IORT) at the Graz University Clinics: development and dosimetry of an applicator system]. / Intraoperative Strahlentherapie (IORT) an den Universitätskliniken Graz: Entwicklung und Dosimetrie eines Applikatorsystems.

The use of high energy electron beams for intraoperative radiotherapy necessitates special technical adjustments of the conventional megavolt equipment. At the University Clinic of Radiology, Division of Radiotherapy in Graz, an applicator system for electron energies up to 20 MeV and cone diameters up to 14 cm was developed. A self modified commercial operating table was used instead of the treatment couch to guarantee optimum mobility for the docking maneuver. The technical set-up of this adaptor system as well as the dosimetric considerations and calculations will be presented in detail.

Intraoperative radiation with external irradiation: an alternative for nonresectable non-small-cell lung cancer?

In 15 patients with nonresectable non-small-cell lung carcinoma (NSCLC) (10 squamous, 1 large cell, 4 adenocarcinomas; T1-T3, N0-N2, all M0), lymph node dissection and intraoperative irradiation of the tumour (IORT) with doses between 10 and 20 Gy (11-20 MeV electron beam) was performed. Four weeks postoperatively 46-56 Gy external irradiation (8 or 23 MeV photons) was delivered to the mediastinum and 46 Gy to the tumour-bearing area. Four weeks postoperatively, 8 minor responses (MR, tumour regression between 4% and 45%) and 6 partial responses (PR, 50%-84%) were found. In 1 case, CT was inconclusive. Eighteen weeks after IORT, volumetry showed 3 CR, 9 PR (62% to 94%) and 1 28% MR. One patient died from intrabronchial hemorrhage 7 weeks after IORT (50% PR). Two others (both CR) died from unrelated causes, 6 and 12 months, respectively, after IORT. One patient (62% PR) died after 14 months from an unknown cause. Another patient died at 15 months from local relapse after CR. The latest CT volume assessment between 7.5 and 21.5 months, respectively, yielded 8 CR, and 1 63% PR. One further case of local CR has developed contralateral pulmonary metastasis after 10 months. All these patients are alive and well. The median time elapsed since IORT is 12.5 months, 10 patients have survived more than 12 months.

99mTc-labeled monoclonal anti-carcinoembryonic antigen antibody (BW 431/26). Clinical results in the detection of colorectal carcinomas and recurrences.

With the introduction of 99mTc-labeled monoclonal antibodies against carcinoembryonic antigen (CEA) a clinically relevant extension can be expected in the diagnosis of colorectal tumors by immunoscintigraphy (IS). This study comprises a total of 49 patients (primary colorectal tumors, occult neoplasms, and suspicious recurrences), in whom IS with 99mTc monoclonal antibody (MAb) BW 431/26 was performed. After injection of 1100 MBq 99mTc MAb BW 431/26 a whole-body scan was performed in anterior and posterior projection 5 1/2 h later, and SPECT of the abdominal region was done after 6 and 24 h. In the course of primary tumor identification (n = 20) all coloscopically diagnosed and operatively verified carcinomas were confirmed and correctly localized by IS (n = 11). In three patients with positive IS and suspicious coloscopic findings surgery was refused by patients and relatives. In five cases IS was true negative and in 1 case false positive. In the diagnosis of recurrences (n = 29) IS showed an uptake in computer-tomographically and coloscopically suspicious areas in 17 cases. In 12 cases IS was rated negative (11 true-negative findings in scar and granulation tissue, 1 false-negative finding in para-aortal lymph nodes). Elevated serum CEA levels were found only in 17 of 31 patients with true-positive IS. In postoperative cancer care IS with 99mTc-labeled anti-CEA antibody plays a preeminent role in the exclusion or identification of colorectal recurrences.