The effect of mycophenolate mofetil on podocytes in nephrotoxic serum nephritis.

Mycophenolate mofetil (MMF) is applied in proteinuric kidney diseases, but the exact mechanism of its effect on podocytes is still unknown. Our previous in vitro experiments suggested that MMF can ameliorate podocyte damage via restoration of the Ca2+-actin cytoskeleton axis. The goal of this study was to characterize podocyte biology during MMF treatment in nephrotoxic serum (NTS) nephritis (NTN). NTN was induced in three-week old wild-type mice. On day 3, half of the mice were treated with MMF (100 mg/kgBW/d p.o.) for one week. On day 10, we performed proteomic analysis of glomeruli as well as super-resolution imaging of the slit diaphragm. For multiphoton imaging of Ca2+ concentration ([Ca2+]i), the experimental design was repeated in mice expressing podocyte-specific Ca2+ sensor. MMF ameliorated the proteinuria and crescent formation induced by NTS. We identified significant changes in the abundance of proteins involved in Ca2+ signaling and actin cytoskeleton regulation, which was further confirmed by direct [Ca2+]i imaging in podocytes showing decreased Ca2+ levels after MMF treatment. This was associated with a tendency to restoration of podocyte foot process structure. Here, we provide evidence that MPA has a substantial direct effect on podocytes. MMF contributes to improvement of [Ca2+]i and amelioration of the disorganized actin cytoskeleton in podocytes. These data extend the knowledge of direct effects of immunosuppressants on podocytes that may contribute to a more effective treatment of proteinuric glomerulopathies with the least possible side effects.

A unitary perturbation theory approach to real-time evolution problems.

We discuss a new analytical approach to real-time evolution in quantum many-body systems. Our approach extends the framework of continuous unitary transformations such that it amounts to a novel solution method for the Heisenberg equations of motion for an operator. It is our purpose to illustrate the accuracy of this approach by studying dissipative quantum systems on all timescales. In particular, we obtain results for non-equilibrium correlation functions for general initial conditions. We illustrate our ideas for the exactly solvable dissipative oscillator and, as a non-trivial model, for the dissipative two-state system.

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.

Reduction of the dose to the lens in prophylactic cranial irradiation: a comparison of three different treatment techniques and two different beam qualities.

Three treatment techniques using two beam qualities have been compared on the basis of dose to the lens in prophylactic cranial irradiation. The dose to the lens and the globe was measured with thermoluminescent crystals in an anthropomorphic phantom and calculated by a computer-assisted planning system. A comparison was made of large field and small field techniques using 60Co and 8 MV photons. Modifications to the basic techniques studied included angulation of the gantry, angulation of the couch, and placement of an additional eye block close to the surface. The dose to the lens could be reduced to four percent of the midplane dose by applying the small-field technique combined with the use of 8 MV energy photons, by placing an additional block close to the surface, and by five degree occipitally angling the gantry, as well as rotating the treatment couch to account for the divergence of the beam. The use of 60Co produced an underdosage of the posterior segment of the globe in angled treatment techniques.

Prognostic factors in patients with carcinoma of the uterine cervix treated with external beam irradiation and IR-192 high-dose-rate brachytherapy.

PURPOSE: Prognostic factors in cancer of the cervix for patients treated with external beam irradiation (EBR) and low-dose-rate (LDR) brachytherapy have been characterized. However, despite the increasing use of high-dose-rate (HDR) intracavitary placements (ICP), few studies with adequate follow-up have analyzed prognostic factors. This study investigates pretreatment and treatment factors for their correlation with treatment outcome after EBR and HDR-ICP. METHODS AND MATERIALS: Between September 1985 and December 1994, 181 patients with carcinoma of the cervix FIGO stages IB-IV received EBR and HDR brachytherapy. Hemoglobin (Hb) levels were maintained above a level of 11 g/dl during the treatment by transfusion. Patient age ranged from 34 to 84 years (median: 66). The median follow-up time for patients at risk is 69 months (range: 23-140). Pretreatment and treatment parameters analyzed to determine their prognostic value included age, FIGO stage, tumor size, tumor type and grade, pretreatment Hb level, number of HDR-ICP, total dose from HDR-ICP, overall dose to point A, and overall treatment time. Also evaluated was the prognostic value of enlarged lymph nodes noted on pretreatment CAT scan of the abdomen and pelvis. Endpoints studied in uni- and multivariate analyses were disease-specific survival (DSS), freedom from disease (FFD), pelvic control (PC), and probability of distant metastases (DM). RESULTS: At 5 years the DSS, FFD, and PC rates for all patients were 60%, 58%, and 67%, respectively. The 5-year FFD by stage was: IB: 94%; II: 63%; IIIB: 43%; and IV: 0%. The PC rates were 94%, 66%, 59%, and 0%, respectively. In univariate analysis the prognostic factors identified for FFD were FIGO stage, tumor size, initial Hb level, and enlarged pelvic and/or paraaortic nodes (all: p < 0.0001). Age was inversely correlated with outcome (p = 0.0081). The 5-year FFD rates for tumors (< 3, > or = 3 < 6, > or = 6 cm) were 97%, 65%, and 24%; patients with initial Hb levels < or = 11g/dl had a FFD of 26% versus 69% for patients with levels > 11g/dl; and those with pelvic and/or paraaortal nodes > or = 1 cm had a survival of 32% versus 68% in patients with negative readings. The same factors were also prognostically significant for DSS, PC, and DM. Patients with persistent disease or pelvic failures had a significantly higher incidence of DM than patients in whom pelvic disease was controlled (p < 0.0001).Histological and treatment parameters including overall treatment time were not of prognostic significance for any of the endpoints studied. In multivariate analysis tumor size was the most powerful parameter for DSS, FFD, PC (p < 0.0001) and DM (p = 0.0001), followed by low initial Hb level (DSS: p = 0.0004, FFD: p = 0.0009, PC: p = 0.0012, DM: p = 0.0265), and enlarged pelvic and/or paraaortic nodes which were predictive for DSS (p = 0.0210) and DM (p = 0.0011). CONCLUSION: This study confirms that prognostic factors for patients treated with HDR brachytherapy are similar to those reported in previous series that employed LDR brachytherapy. The significance of tumor size, pretreatment Hb level, and enlarged pelvic and/or paraaortic lymph nodes on CAT scan over FIGO stage of disease were demonstrated. Future prospective trials should be undertaken to confirm the validity of these factors and to elucidate their therapeutic implications.

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.

Dosimetry of intracavitary placements for uterine and cervical carcinoma: results of orthogonal film, TLD, and CT-assisted techniques.

A total of 720 192Ir high-dose-rate (HDR) applications in 331 patients with gynecological tumors were analyzed to evaluate the dose to normal tissues from brachytherapy. Based on the calculations of bladder base, bladder neck, and rectal doses derived from orthogonal films the planned tumor dose or fractionation was altered in 20.4% of intracavitary placements (ICP) for cervix carcinoma and 9.2% of ICP for treatment of the vaginal vault. In 13.8% of intracervical and 8.1% of intravaginal treatments calculated doses to both the bladder and rectum were greater than or equal to 140% of the initially planned dose fraction. Doses at the bladder base were significantly higher than at the bladder neck (p less than 0.001). In 17.5% of ICP the dose to the bladder base was at least twice as high as to the bladder neck. The ratio of bladder base dose to the bladder neck was 1.5 (+/- 1.19 SD) for intracervical and 1.46 (+/- 1.14 SD) for intravaginal applications. The comparison of calculated doses from orthogonal films with in-vivo readings showed a good correlation of rectal doses with a correlation coefficient factor of 0.9556. CT-assisted dosimetry, however, revealed that the maximum doses to bladder and rectum were generally higher than those obtained from films with ratios of 1-1.7 (average: 1.44) for the bladder neck, 1-5.4 (average: 2.42) for the bladder base, and 1.1-2.7 (average: 1.37) for the rectum. When doses to the specified reference points of bladder neck and rectum from orthogonal film dosimetry were compared with the corresponding points on CT scans, similar values were obtained for both methods with a maximum deviation of +/- 10%. Despite the determination of multiple reference points our study revealed that this information was inadequate to predict doses to the entire rectum and bladder. If conventional methods are used for dosimetry it is recommended that doses to the bladder base should be routinely calculated, since single point measurements at the bladder neck seriously underestimate the dose to the bladder. Also the rectal dose should be determined at several points over the length of the implant due to the wide range of anatomic variations possible.

Carcinoma of the cervix: analysis of complications after primary external beam radiation and Ir-192 HDR brachytherapy.

BACKGROUND AND PURPOSE: There is still a concern that the use of HDR brachytherapy might result in an increase of late tissue damage. This restrospective study evaluates the incidence and severity of late complications in patients with carcinoma of the cervix who underwent combined external beam radiation (EBR) and Ir-192 HDR brachytherapy and attempts to identify pretreatment and treatment parameters correlating with late complications. MATERIAL AND METHODS: Between 1985 and 1992, 161 patients with carcinoma of the cervix (FIGO stages IB-IVB) received EBR to the pelvis (ave, max. dose 48.8 Gy) followed by 1-6 Ir-192 HDR placements (median 2). Doses to point A ranged from 8.5 to 38.7 Gy (median 17 Gy). Parameters examined included age, diabetes, obesity, history of inflammatory bowel disease or diverticulitis, prior surgery, hemoglobin level, FIGO stage, EBR dose, technique and daily dose fraction, number of HDR treatments and total dose to point A, maximum doses to bladder and rectum delivered by brachytherapy and cumulative dose to point A. Median follow-up for all patients was 37 months. Complications were rated using an in-house scoring system and according to the French-Italian Glossary (FIG). RESULTS: Actuarial 5-year survival was 93%, 57%, 46%, and 0% for stages IB, II, IIIB, and IV, respectively. Of 161 patients, 11% developed moderate and 3.7% severe sequelae (FIG: 2.5%, 3.7%). Since some patients experienced more than one complication, the overall incidence was 13.6% and 4.9% (FIG: 3.1%, 4.9%) with respective 5-year actuarial rates of 14% and 5% for moderate, and 2% and 8% for severe bowel and genitourinary tract complications (FIG: 3.5%, 0, and 2%, 8%). All severe bowel complications occurred within 1.5 years whereas urinary tract sequelae continued to develop throughout the follow-up period. FIGO stage was associated with a significant increase in late sequelae (P = 0.015). Analysis of the remaining pretreatment and treatment parameters failed to reveal any statistically significant correlation with moderate or severe sequelae. CONCLUSION: In our series using HDR brachytherapy, complication and survival rates were comparable with other series employing either LDR or HDR procedures. Of all parameters analysed, stage of disease was the only parameter significantly correlated with complications in univariate and multivariate analysis.

Adjuvant radiotherapy in male breast cancer.

PURPOSE: To determine retrospectively the outcome of postoperative radiation therapy in male breast cancer. Local/distant control was assessed with attention to age, stage, lymph node involvement, histopathological differentiation and hormone receptor status. MATERIALS AND METHODS: Thirty-one male patients were irradiated postoperatively at the chest wall (mean dose 50 Gy) and 16 patients received radiation to regional lymph nodes. Tumour distribution by stage was: stage 0 (9.7%), stage I (22.6%), stage II (32.2%) and stage III (35.5%). Nine patients were subjected to additional hormone therapy and three patients to chemotherapy. RESULTS: Local control was achieved in 30/31 (96.8%) patients. Kaplan-Meier estimates of overall survival (OS), disease specific (DSS) and disease free survival (DFS) at 5 years were 77% (95% confidence interval (CI), 0.61-0.93), 84% (CI, 0.69-0.98) and 73% (CI, 0.57-0.91), respectively. Five-year DFS for stage 0 + I, II and III was 100, 56.3 and 67.3%, respectively. Favourable results were observed in patients with negative axillary nodes with 5-year OS/DFS of 90.9% (CI, 0.74-1.0). For lymph node positive patients DFS was 71% (CI, 0.4-1.0). Patients who presented lymph node metastases with extracapsular extension the 5-year OS was 80% (CI, 0.45-1.00), but the DFS was 0%. Stage of disease, lymph node involvement and histological differentiation were found to have statistically significant influence on DFS, but not on OS. CONCLUSION: Application of postoperative radiotherapy approved in females resulted in one local relapse in our study population. Other treatment modalities (hormone therapy/chemotherapy) should continue to be considered a necessary treatment option for appropriately selected patients.

Hyperbaric oxygen--an effective tool to treat radiation morbidity in prostate cancer.

PURPOSE: We report the results of hyperbaric oxygen therapy (HBO) used in the treatment of radiation cystitis and proctitis following irradiation of prostate cancer. MATERIALS AND METHODS: Between June 1995 and March 2000, 18 men (median age 71 years) with radiation proctitis (n=7), cystitis (n=8), and combined proctitis/cystitis (n=3) underwent HBO therapy in a multiplace chamber for a median of 26 sessions (range 2-60). The treatment schedule (2.2-2.4 atmospheres absolute, 60 min bottom time, once-a-day, 7 days a week) was set at a lower limit of 20 sessions; the upper limit was left open to symptom-related adjustment. Prior to HBO treatment, RTOG/EORTC late genitourinal (GU) morbidity was Grade 2 (n=3), Grade 3 (n=6) or Grade 4 (n=2); modified RTOG/EORTC late gastrointestinal (GI) morbidity was either Grade 2 (n=4) or Grade 3 (n=6). RESULTS: Sixteen patients underwent an adequate number of sessions. RTOG/EORTC late GU as well as modified GI morbidity scores showed a significant improvement after HBO (GI, P=0.004; GU, P=0.004; exact Wilcoxon signed rank test); bleeding ceased in five out of five patients with proctitis and in six out of eight patients with cystitis; one of those two patients, in whom an ineffective treatment outcome was obtained, went on to have a cystectomy. CONCLUSIONS: HBO treatment seems to be an effective tool to treat those patients with late GI and GU morbidity when conventional treatment has led to unsatisfactory results. Particularly in patients with radiation cystitis, HBO should not be delayed too long, as in the case of extensive bladder shrinkage improvement is hard to achieve.

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.

Postoperative radiotherapy in radically resected non-small cell lung cancer.

PURPOSE: To evaluate the value of adjuvant postoperative external-beam radiation (EBR) in patients with radically resected non-small cell lung cancer (NSCLC) pT1-3 pN0-2 compared to patients with resected NSCLC without adjuvant EBR. MATERIALS AND METHODS: In 155 patients (121 male, 34 female; mean age, 59 years) 105 lobectomies, 12 bilobectomies, and 38 pneumonectomies with radical lymph node dissection of the contralateral [corrected] side were performed. Postoperative staging was done according to the TNM system and was as follows: pT1 (n=38), pT2 (n=89), pT3 (n=28); pN0 (n=39), pN1 (n=67) and pN2 (n=49). Histopathologic study revealed 68 squamous cell carcinomas, 53 adenocarcinomas, 21 large cell carcinomas, 6 adenosquamous cell carcinomas, and 7 bronchioloalveolar cell carcinomas. All patients were randomly assigned into two treatment groups: 72 patients with no further treatment (control group), and 83 patients (EBR group) with adjuvant postoperative EBR of the bronchial stump and mediastinum (50 to 56 Gy, 8 or 23 MV photons, 2 Gy/d, 5 d/wk) beginning 4 to 6 weeks after surgery. RESULTS: The overall 5-year survival rate (median observation time, 43 months) of all patients was 24.1% (EBR group, 29.7%; control group, 20.4%; p>0.05, not significant). The relative risk of the EBR group was 0.85 with a two-sided confidence interval of 0.66 to 1.09. The overall 5-year recurrence-free survival was 20.6% (EBR, 27.1%; control group, 15.6%; p=0.07). The relative risk of the EBR group was 0.80 with a confidence interval of 0.63 to 1.01. The rate of local recurrences at the bronchial stump and/or mediastinum was significantly smaller in the EBR group (n=5) than in the control group (n=17) (p<0.01). Multivariate analysis (chi2 test) demonstrated an independent influence of postoperative EBR on the incidence of local recurrences. The incidence of distant metastases was slightly but not significantly higher in patients without EBR (38 patients) compared to those who had EBR (32 patients). CONCLUSION: High-dose postoperative EBR to the mediastinum significantly reduces the risk of local recurrence at the bronchial stump and/or mediastinum. Age, sex, histologic subtype, tumor size, surgical approach, or extent of lymph node involvement had no prognostic value--only postoperative EBR had an independent influence on the risk of local recurrence. The effect of postoperative EBR was on the verge of significance with respect to recurrence-free survival and showed the same tendency in overall survival, however with an attenuated relative risk.

Endocavitary Ir-192 radiation and laser treatment for palliation of obstructive rectal cancer.

Endoscopic laser therapy (ELT) either alone or combined with endocavitary Ir-192 radiation is performed for advanced, inoperable rectal cancer and when patients are ineligible for surgery due to severe concomitant medical illness. During the period from January 1984 to January 1997 we treated 81 patients (51 males, 30 females). Sixty-seven patients had ELT only using a ND-Yag Laser system. Twenty-five patients (average age: 80.5 years) were ineligible for surgery (Group I). Forty-two patients (74.1 years) had an advanced locally inoperable tumour (Group II). Fourteen patients (76.5 years) underwent a combined therapeutic regime with endocavitary Ir-192 afterloading following ELT (Group III). Adequate desobliteration was achieved in 100% (groups I and III) and 97% (group II) of the patients. The average interval to aftertreatment was 8.4 weeks in group I and 9.4 weeks in group II, compared to 11.5 weeks in group III. Serious complications (perianal abscess, rectovaginal fistula) occurred in 3.7%, minor complications (laser-induced bleedings, unclear fever) in 12.3%. All laser-induced bleedings could be dealt with using laser therapy. The frequency of treatment was governed by tumour mass and the patient's survival. The results suggest that additional endocavitary radiation significantly prolongs the maintenance of normal bowel function compared with laser therapy alone.

Evaluating intraoperative radiation therapy (IORT) and external beam radiation therapy (EBRT) in non-small cell lung cancer (NSCLC). Five years experience.

A pilot study on intraoperative radiation therapy (IORT) combined with external beam radiation therapy (EBRT) in nonresectable non-small cell lung cancer (NSCLC) was performed in 31 patients (mean age: 66.2 years, range: 51-80; 10 anatomically and functionally, 21 functionally, nonresectable; 20 squamous-cell, 11 adenocarcinoma). The tumor was exposed by lateral thoracotomy and a staging lymph node dissection was performed (final staging 7 T1, 16 T2, 8 T3; 11 nodal positive). Ten to 20 Gy IORT (energy: 7-20 MeV electrons) were delivered to the tumor. Unilateral continuous positive airway pressure ventilation of the diseased lung was used to reduce the amount of healthy lung tissue in the IORT port and to minimize the ventilatory movement. Secondary collimation and direct shielding of radio-sensitive structures within the IORT port by aluminium sheets were used to further reduce collateral damage. Four weeks after IORT, 46 Gy EBRT (2 Gy/day 5 times a week; 8-23 MeV photons) were administered to the mediastinum and to the tumor-bearing area on an outpatient basis. In nodal positive cases the mediastinal dose was increased to 56 Gy. Twenty-three patients were evaluable. In 13 complete, in 8 partial (50-97% regression) and in 2 minor response has been achieved. Five patients experienced a recurrence (local only: 2; local and distant: 1; distant only: 2). Twelve patients died of underlying cardio-respiratory disorders within 6 to 25 months after IORT; 7 died of cancer. The overall 5-year survival rate including the incidental deaths is 14.7%. The recurrence-free survival rate is 53.2%.

"Adjuvant" external radiation of the mediastinum in radically resected non-small cell lung cancer.

OBJECTIVE: The effect of postoperative external beam radiation in MO non-small cell lung cancer resected with curative intention was evaluated in a randomized trial. METHODS: In 155 patients (121 males, 34 females; mean age: 59 years) 105 lobectomies, 12 bilobectomies and 38 pneumonectomies with radical lymph node dissection to the contralateral side were carried out. Histology revealed squamous cell (n = 68), adeno- (n = 53), large cell (n = 21), adenosquamous (n = 6) or bronchioloalveolar type (n = 7) carcinomas. The pathologic stages T1 (n = 38), T2 (n = 89), T3 (n = 28); NO (n = 39), N1 (n = 67), and N2 (n = 49) were evenly distributed between the two treatment groups: group A (72 patients) had no further oncologic treatment, while group B (83 patients) had external beam radiation to the mediastinum (50-56 Gy, 8 or 23 MeV photons, 2 Gy/day, 5 days a week) beginning 4 weeks after the operation. RESULTS: The overall 5-year survival rate of the whole collective was 24.1% without any significant difference between the radiotherapy group B (29.7%) and the control group A (20.4%) (log-rank test: P > 0.05). The overall 5-year recurrence-free survival rate was 20.1%, with no difference between groups B and A (radiotherapy: 22.7, controls: 15.6%, long-rank test: P > 0.05). There was no difference in the incidence of distant metastases (external beam radiation: n = 32; controls: n = 38). The rate of local recurrences at the bronchial stump or in the mediastinum, however, was significantly reduced in the radiotherapy group (n = 5) compared with 17 in the controls (P < 0.01 chi-square test). A multivariate analysis confirmed the independent influence of postoperative radiotherapy on the incidence of local recurrence. CONCLUSIONS: External radiation of the mediastinum in radically resected non-small cell lung cancer reduces the risk of local recurrence, but has no influence on distant metastastic spread and overall survival.

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.

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.

Iridium-192 high dose rate brachytherapy combined with external beam irradiation in non-resectable oesophageal cancer.

Forty-eight patients with non-resectable cancer of the oesophagus and oesophagogastric junction (group A: Stage I/II: n = 32; group B: Stage III/IV: n = 16) underwent intralumenal iridium-192 high dose-rate afterloading brachytherapy (5-7 Gy/session, total dose 5-21 Gy, mean 12.4 Gy) and external beam irradiation (Karnofsky > or = 80%: 50-60 Gy/2 Gy per day; Karnofsky 60%-79%: 30 Gy/3 per day). Prolonged satisfactory palliation (intake of at least semi-solid food) was demonstrated in 96% of patients. The mean survival for group A was 19.1 months and that for group B 6.9 months, with a 12-month survival rate of 66% for group A and 0% for group B (P < 0.001). Local tumour response and complication rate were significantly dose related with a predicted response rate of 70.5% and a complication rate of 50% at extrapolated response dose (ERD) 129.3 GY3 (Gy at alpha/beta = 3).

[Metastatic involvement of the breast]. / Metastatischer Befall der Mamma.

The mammographic spectrum of metastases in the breast is illustrated by 43 cases with histologically confirmed findings. Haematogenous metastases appear as sharply demarcated foci, lymphogenous metastases produce thickening of the skin and reticular thickening of the subcutis and of the glandular tissue. Metastases from systemic haematological disease may appear in nodular or diffuse form.

[Intracranial germinoma; typical CT appearances and radiation therapy (author's transl)]. / Intrakranielles Germinom: Typisches computertomographisches Bild und Strahlentherapie.

The typical CT appearances of intracranial germinomas are described in three cases. These consist of an isodense or hyperdense tumour in the mid-line, originating from the pineal body or infundibulum, with marked increase in density on contrast enhancement. Periventricular tumour expansion in relation to the entire supratentorial ventricular system is characteristic. The rapid tumour regression after small doses of radiation is stressed and complete regression of the tumour, as seen on CT, is a sign of its radio-curability.