Individual radiosensitivity measured with lymphocytes may predict the risk of acute reaction after radiotherapy.

PURPOSE: We tested whether the chromosomal radiosensitivity of in vitro irradiated lymphocytes could be used to predict the risk of acute reactions after radiotherapy. METHODS AND MATERIALS: Two prospective studies were performed: study A with 51 patients included different tumor sites and study B included 87 breast cancer patients. Acute reaction was assessed using the Radiation Therapy Oncology Group score. In both studies, patients were treated with curative radiotherapy, and the mean tumor dose applied was 55 Gy (40-65) +/- boost with 11 Gy (6-31) in study A and 50.4 Gy +/- boost with 10 Gy in study B. Individual radiosensitivity was determined with lymphocytes irradiated in vitro with X-ray doses of either 3 or 6 Gy and scoring the number of chromosomal deletions. RESULTS: Acute reactions displayed a typical spectrum with 57% in study A and 53% in study B showing an acute reaction of Grade 2-3. Individual radiosensitivity in both studies was characterized by a substantial variation and the fraction of patients with Grade 2-3 reaction was found to increase with increasing individual radiosensitivity measured at 6 Gy (study A, p = 0.238; study B, p = 0.023). For study B, this fraction increased with breast volume, and the impact of individual radiosensitivity on acute reaction was especially pronounced (p = 0.00025) for lower breast volume. No such clear association with acute reaction was observed when individual radiosensitivity was assessed at 3 Gy. CONCLUSION: Individual radiosensitivity determined at 6 Gy seems to be a good predictor for risk of acute effects after curative radiotherapy.

High accuracy of virtual simulation with the laser system Dorado CT4.

PURPOSE: To evaluate the accuracy of virtual simulation, which is less time-consuming than physical simulation, with the new laser system Dorado CT4 in 96 prostate cancer patients. PATIENTS AND METHODS: Virtual simulation was based on a spiral scan with 8 mm reconstruction index and 8 mm slice thickness in 64 patients (group A), and 3 mm reconstruction index and 3 mm slice thickness in 32 patients (group B). Both groups were evaluated for impact on maximum difference (Deltamax) regarding the isocenters obtained from virtual simulation versus those obtained from physical simulation. RESULTS: In the entire cohort, mean differences were as follows: Deltamax 5.7 +/- 3.5 mm, Deltax (left/right) 2.8 +/- 2.9 mm, Deltay (anterior/posterior) 4.5 +/- 3.8 mm, and Deltaz (cranial/caudal) 2.1 +/- 2.2 mm. In group A, mean values were Deltamax 6.2 +/- 3.8 mm, Deltax 2.9 +/- 3.1 mm, Deltay 4.9 +/- 4.2 mm, and Deltaz 2.3 +/- 2.3 mm. In group B, mean values were Deltamax 4.8 +/- 2.8 mm, Deltax 2.7 +/- 2.7 mm, Deltay 3.7 +/- 2.7 mm, and Deltaz 1.7 +/- 2.0 mm. Time of radiotherapy (primary vs. salvage RT) and radiation regimen (external-beam radiotherapy [EBRT] vs. high-dose-rate brachytherapy [HDR-BT] plus EBRT) had no significant impact on Deltamax. CONCLUSION: Virtual simulation with the new laser system Dorado CT4 was very precise for both primary and salvage RT in the treatment of prostate cancer patients. High precision was achieved for both EBRT and HDR-BT plus EBRT. Virtual simulation should be performed with a planning CT with 3 mm reconstruction index and 3 mm slice thickness for high accuracy.

Experiences with a new high-dose-rate brachytherapy (HDR-BT) boost technique for T3b prostate cancer.

PURPOSE: Experiences with a new high-dose-rate brachytherapy (HDR-BT) boost technique in 41 patients with stage T3b prostate cancer are presented. PATIENTS AND METHODS: The patients received 18 Gy of HDR-BT (9 Gy on days 1 + 8) plus 50.4 Gy of EBRT. 20 patients (group A) had BT applicators placed into the prostate alone resulting in 18 Gy to prostate and 0 Gy (tip) to 12 Gy (base) to seminal vesicles (SV). The cumulative EQD2 (equivalent dose in 2-Gy fractions, alpha/beta 1.5 Gy) to the SV was 47.5-73.3 Gy. 21 patients (group B) had BT applicators placed into both prostate and SV resulting in 18 Gy to prostate and to > 80% (but not 100%) of the SV (cumulative EQD2 81.5-101.5 Gy). Both groups were compared for acute and late toxicity and for biochemical relapse-free survival (bRFS). RESULTS: The 3-year bRFS was 57% for group A and 79% for group B patients (p = 0.29). A grade 3 acute toxicity (CTC 2.0) was not observed. Grade 2 acute toxicity (proctitis, cystitis, skin toxicity) was comparable in both groups. A grade 3 late toxicity did not occur. Impotence rates were 35% in group A and 24% in group B, respectively (p = 0.73). CONCLUSION: The new HDR-BT technique (group B) was associated only with minor acute and late toxicity and appears to result in better bRFS than the conventional HDR-BT technique (group A). The results must be confirmed in a prospective trial.

Epoetin alfa improves survival after chemoradiation for stage III esophageal cancer: final results of a prospective observational study.

PURPOSE: This prospective, nonrandomized study evaluates the effectiveness of epoetin alfa to maintain the hemoglobin levels at 12 to 14 g/dL (optimal range for tumor oxygenation) during chemoradiation for Stage III esophageal cancer and its impact on overall survival (OS), metastatic-free survival (MFS), and locoregional control (LC). METHODS AND MATERIALS: Ninety-six patients were included. Forty-two patients received epoetin alfa (150 IU/kg, 3 times a week) during radiotherapy, which was started at hemoglobin less than 13 g/dL and stopped at 14 g/dL or higher. Hemoglobin levels were measured weekly during RT. RESULTS: Both groups were balanced for age, sex, performance status, tumor length/location, histology, grading, T-stage/N-stage, chemotherapy, treatment schedule, and hemoglobin before RT. Median change of hemoglobin was +0.3 g/dL/wk with epoetin alfa and -0.5 g/dL/wk without epoetin alfa. At least 60% of hemoglobin levels were 12 to 14 g/dL in 64% and 17% of the patients, respectively (p < 0.001). Patients who received epoetin alfa had better OS (32% vs. 8% at 2 years, p = 0.009) and LC (67% vs. 15% at 2 years, p = 0.001). MFS was not significantly different (42% vs. 18% at 2 years, p = 0.09). CONCLUSIONS: The findings suggest that epoetin alfa when used to maintain the hemoglobin levels at 12 to 14 g/dL can improve OS and LC of Stage III esophageal cancer patients.

Well-differentiated neurocytoma: what is the best available treatment?

Most neurocytomas are well differentiated, being associated with better long-term survival than the more aggressive atypical lesions. Atypical neurocytomas are characterized by an MIB-1 labeling index >3% or atypical histologic features. This analysis focuses on well differentiated neurocytomas in order to define the optimal treatment. A case with a follow-up of 132 months is presented. The patient developed two recurrences two and four years after first surgery, each showing an increasing proliferation activity. Furthermore, all published well-differentiated neurocytoma cases were reviewed for surgery, radiotherapy, and prognosis. Additional relevant data were obtained from the authors. Complete resection (CTR), complete resection plus radiotherapy (CTR + RT), incomplete resection (ITR), and incomplete resection plus radiotherapy (ITR + RT) were compared for outcome by using the Kaplan-Meier method and the log-rank test. Data were complete in 301 patients (CTR, 108; CTR + RT, 27; ITR, 81; ITR + RT, 85). Local control and survival were better after CTR than after ITR (P < 0.0001 and P = 0.0085, respectively). Radiotherapy improved local control after ITR (P < 0.0001) and after CTR (P = 0.0474), but not survival (P = 0.17 and P = 1.0, respectively). In the ITR + RT group, doses < or =54 Gy (n = 33) and >54 Gy (n = 32) were not significantly different for local control (P = 0.88) and survival (P = 0.95). The data demonstrated CTR to be superior to ITR for local control and survival. After CTR and ITR, radiotherapy improved local control, but not survival. A radiation dose of 54 Gy appeared sufficient. Application of postoperative radiotherapy should be decided individually, taking into account the risk of local failure, the need for another craniotomy, and potential radiation toxicity.

Comparison of 1 x 8 Gy and 10 x 3 Gy for functional outcome in patients with metastatic spinal cord compression.

PURPOSE: Since life expectancy is markedly reduced in patients with metastatic spinal cord compression (MSCC), a short and effective radiation schedule is desired. This study investigates a reduction of the overall treatment time to only one day by comparing 1 x 8 Gy to the multi-fractionated 10 x 3 Gy for functional outcome. METHODS AND MATERIALS: Data of 204 patients, treated for MSCC with either 1 x 8 Gy (n = 96) or 10 x 3 Gy (n = 108), were analyzed retrospectively. Motor function and ambulatory status were evaluated before and up to 24 weeks after RT. A multivariate analysis (nominal regression) was performed including radiation schedule, performance status, age, irradiated vertebra, and relevant prognostic factors (histology, ambulatory status, time of developing motor deficits). Improvement of motor deficits was selected as basic category and compared with no change and deterioration. RESULTS: Univariate analysis showed no significant difference between the schedules for post-treatment motor function and ambulatory rates. Multivariate analysis demonstrated a significant effect on functional outcome for the prognostic factors, but not for the radiation schedule (p = 0.853 for no change, p = 0.237 for deterioration). CONCLUSIONS: Our data suggest the two fractionation schedules to be comparably effective for functional outcome. Thus, 1 x 8 Gy should be considered for patients with a poor survival prognosis.

Effectiveness and toxicity of single-fraction radiotherapy with 1 x 8 Gy for metastatic spinal cord compression.

Toxicity and functional outcome were evaluated in 199 MSCC-patients irradiated with 1 x 8 Gy. Motor function improved in 54/199 patients (27%). Patients who regained walking ability were 20/78 (26%). Long-term-survivors (> or =12 months) who needed re-irradiation for in-field-recurrence were 19/65 (29%). Acute toxicity was mild, late toxicity not observed. A randomised trial comparing single-fraction RT to multi-fraction RT is mandatory.

Neutron therapy, prognostic factors and dedifferentiation of adenoid cystic carcinomas (ACC) of salivary glands.

PURPOSE: Analysis of the efficacy of fast neutron radiotherapy in the treatment of adenoid cystic carcinomas (ACC) of the salivary glands, identification of prognostic variables and dedifferentiation after radiotherapy. PATIENTS AND METHODS: Histological slides of primary and recurrent lesions of 71 patients were reviewed to confirm the diagnosis and to analyse subtypes. Median follow-up was 52 months. Local control rate and overall survival were analysed in multivariate analysis. Complications are also described. RESULTS: Primary vs. recurrent therapy (p=0.001), margin-status (p=0.01) and subtype (p=0.019) influenced overall survival. Primary vs. recurrent therapy (p=0.001), margin-status (p=0.018) and T-stage (p=0.043) influenced local control rate. Dedifferentiation was seen in only 1/17 cases. CONCLUSION: The calculated prognostic factors illustrate the importance of a radical primary therapy. Histological subtype is a significant additional factor for overall survival and, in case of dedifferentiation, it is a strong predictor of a detrimental outcome.

Role of radiotherapy in the treatment of motor dysfunction due to metastatic spinal cord compression: comparison of three different fractionation schedules.

PURPOSE: The optimum fractionation schedule for radiotherapy (RT) of metastatic spinal cord compression (MSCC) is still debated in the literature. Several reports have compared different fractionation schedules for pain relief. To our knowledge, this retrospective analysis is the first to compare three different schedules for functional outcome. METHODS AND MATERIALS: For posttreatment functional and ambulatory outcome, three schedules, 30 Gy in 10 fractions (n = 93), 37.5 Gy in 15 fractions (n = 80), and 40 Gy in 20 fractions (n = 74), were compared. Motor function was evaluated by a 6-point scale before and at the end of RT and 3, 6, and 12 months later. A multivariate analysis was performed for functional outcome, including fractionation schedule and the three relevant prognostic factors (primary tumor type, time of developing motor deficits before RT, and ambulatory status). RESULTS: No significant difference was observed for posttreatment motor function or ambulatory rates among the three schedules. According to the multivariate analysis, the radiation schedule had no significant impact on functional outcome (p = 0.223) in contrast to the three prognostic factors (p <0.001, p <0.001, and p = 0.012). CONCLUSION: The three fractionation schedules were comparable for functional outcome. The least time-consuming schedule (30 Gy in 10 fractions) should be considered for patients with a markedly reduced life expectancy.

Is there a dose-effect relationship for the treatment of symptomatic vertebral hemangioma?

PURPOSE: Symptomatic vertebral hemangiomas are rare vascular lesions. Radiotherapy is the most common treatment. Because of a lack of information in the literature, uncertainty exists about the total radiation dose to be applied. METHODS AND MATERIALS: Individual data from our own and published patients with symptomatic vertebral hemangioma treated with radiotherapy alone were obtained. The data were pooled, and the impact of the total dose on complete pain relief was evaluated using the chi-square test. Because different single-fraction doses were used, the equivalent dose in 2-Gy fractions (EQD(2)) was used for the analysis. RESULTS: Complete data could be obtained from 117 patients. Patients were categorized according to total dose (EQD(2)) into two groups of similar size (Group A: 20-34 Gy, n = 62; and Group B: 36-44 Gy, n = 55). Radiation-induced complete pain relief was achieved in 39% (24/62) of the patients in Group A and in 82% (45/55) of the patients in Group B. The difference was statistically significant (p = 0.003). CONCLUSIONS: The data suggest a dose-effect relationship in the radiotherapy of symptomatic vertebral hemangiomas. We recommend a total radiation dose 36-40 Gy with a dose per fraction of 2.0 Gy.

Long-term radiation sequelae after breast-conserving therapy in women with early-stage breast cancer: an observational study using the LENT-SOMA scoring system.

PURPOSE: To evaluate the long-term toxicity after breast-conserving therapy in women with early-stage breast cancer. METHODS AND MATERIALS: Late toxicity according to the late effects of normal tissue-subjective, objective, management, and analytic (LENT-SOMA) criteria and cosmetic outcome (graded by physicians) were evaluated in 590 of 2943 women with early-stage breast cancer who were irradiated between 1983 and 1995 using the following fractionation schedules: group A, 1983-1987, 2.5 Gy 4x/wk to 60 Gy; group B, 1988-1993, 2.5 Gy 4x/wk to 55 Gy, group C, 1994-1995, 2.0 Gy 5x/wk to 55 Gy. RESULTS: LENT-SOMA Grade 3-4 toxicity was observed as follows: group A (median follow-up 171 months; range 154-222 months), fibrosis 16% (7 of 45), telangiectasia 18% (8 of 45), and atrophy 4% (2 of 45); group B (median follow-up 113 months; range 78-164 months), pain 2% (8 of 345), fibrosis 10% (34 of 345), telangiectasia 10% (33 of 345), arm edema 1% (2 of 345), and atrophy 8% (27 of 345); and group C (median follow-up 75 months, range 51-96 months, n = 200), occurrence of Grade 3-4 late morbidity

Increasing the rate of late toxicity by changing the score? A comparison of RTOG/EORTC and LENT/SOMA scores.

PURPOSE: The Radiation Therapy Oncology Group (RTOG) and Late Effects Normal Tissue Task Force subjective, objective, management, and analytic (LENT/SOMA) scores were compared in a group of breast cancer patients. The impact of the classification system on grading late effects was evaluated. MATERIALS AND METHODS: Telangiectasia, skin pigmentation, and fibrosis were scored according to both LENT/SOMA and RTOG criteria. The results were compared with respect to up- or downgrading and correlated (Spearman's rho). Other side effects were recorded using LENT/SOMA criteria. Interobserver variability was calculated with Cohen's kappa. Two hundred fifty-nine subsequent relapse-free patients who underwent breast-conserving therapy between 1981 and 1995 were examined. The median dose of radiotherapy to the breast was 55 Gy. Adjuvant chemotherapy was given to 31 patients and tamoxifen to 52 patients. The median follow-up was 8 years. RTOG skin and s.c. tissue scales and LENT/SOMA breast and pigmentation scales were used. Two doctors examined 45 patients jointly. RESULTS: Of all patients, 20% had telangiectasia, 22% pigmentation, 43% fibrosis, 4% breast edema, 77% retraction/atrophy, and 54% pain. In comparison, when LENT/SOMA criteria were used, telangiectasia and pigmentation were upgraded in 34% and 36%, respectively, and telangiectasia was downgraded in 45%. Fibrosis correlated well (Spearman's rho 0.78, p = 0.01). An additional 356 side effects, mainly retraction/atrophy were observed in 226 patients using LENT/SOMA criteria. Interobserver variability was similar for both classification systems and ranged from Cohen's kappa 0.3 (retraction) to 0.91 (telangiectasia). CONCLUSIONS: LENT/SOMA criteria seem to be the better tool in grading and recording late radiation toxicity compared with the RTOG scale. There was some upgrading with the RTOG score when skin toxicity is evaluated. In contrast, fibrosis scores correlated very well. Adjustments of the LENT/SOMA scoring system should be considered to standardize reporting of late radiation morbidity.

Cosmesis from the patient's and the doctor's view.

PURPOSE: Long-term cosmesis from the patient's perspective is compared to the doctor's appraisal. Factors that determine judgment of cosmesis are analyzed. Also, a patient questionnaire was designed to screen for normal tissue reactions and is evaluated. METHODS AND PATIENTS: With structured questions, patients rated their satisfaction considering cosmesis, the difference in overall appearance, and specific changes of the breast. Two doctors rated cosmesis and radiation late effects (LENT/SOMA). Ratings were compared, and the relative impact of single items was studied. Two hundred eighty-seven patients with unilateral breast carcinoma were examined after a median follow-up of 8 years. They were treated between 1981 and 1995 with lumpectomy and radiotherapy of the breast with 1.8-2.5 Gy fractions with a median total dose of 55 Gy (range: 50-65 Gy). RESULTS: One hundred sixty-one patients rated cosmesis as satisfying, 73 patients rated it as acceptable, and 25 patients as poor. Eighty-nine patients noted severe changes of appearance. Severe firmness and extensive scars were the most frequent complaint; the most important single item for judging cosmesis as poor was highly visible scars. Generally, doctors rated cosmesis less favorably (satisfactory, 150 patients; poor, 43 patients). Severe fibrosis was more important than discoloration of the breast or scars. Correlation between patients' and doctors' rating of cosmesis was modest (Cohen's weighted kappa 0.29), whereas the doctor's rating correlated well (0.55). Specificity and sensitivity of the questionnaire item for severe fibrosis (using doctors' judgments as gold standard) was 0.8; Cohen's weighted kappa was 0.34 (95% confidence interval: 0.21-0.48). CONCLUSION: Rating of cosmesis is subjective. Patients' satisfaction with cosmesis is greater than the doctors' and is determined not only by radiation late effects, but also by factors unrelated to the appearance of the breast. Severe fibrosis may be detected by a patient questionnaire.

Radiotherapy after high-dose chemotherapy and peripheral blood stem cell support in high-risk breast cancer.

PURPOSE: To assess the toxicity and efficacy of radiotherapy with respect to locoregional control after adjuvant high-dose chemotherapy for patients with breast cancer. At first, radiotherapy was withheld because of toxicity concerns, but it was introduced in 1995 because of reported high locoregional relapse rates. METHODS AND MATERIALS: Between 1992 and 1998, 40 patients with Stage II-III high-risk breast cancer received adjuvant high-dose chemotherapy consisting of thiotepa, mitoxantrone, and cyclophosphamide and peripheral blood stem cell support after four cycles of induction chemotherapy. The chest wall or breast, as well as the supraclavicular nodes, were irradiated with electrons and photons to a median dose of 50.4 Gy in 20 patients. Six additional patients received only supraclavicular irradiation to a median dose of 50.4 Gy. Acute toxicity was scored clinically. Pulmonary function tests were performed in 14 irradiated patients before high-dose chemotherapy and 1.1-4.4 years (median 1.6) after irradiation. The median follow-up time of living patients was 33 vs. 67 months in irradiated (n = 26) and nonirradiated (n = 14) patients, respectively. RESULTS: G2 and G3 hematologic toxicity occurred in 1 patient each. No clinical pneumonitis or clinical impairment of lung function was observed. After 1-2 years, the lung function tests showed only minor changes in 4 patients. The 3-year locoregional control rate was 92% in the irradiated patients vs. 58% in the nonirradiated patients (p = 0.049, actuarial analysis). CONCLUSION: In this series, adjuvant radiotherapy after adjuvant chemotherapy for breast cancer appeared well tolerated, with improved local regional control and without significant side effects. Longer follow-up and more patient accrual, as well as Phase III trials, are necessary for confirmation.

Serious adverse effects of amifostine during radiotherapy in head and neck cancer patients.

BACKGROUND AND PURPOSE: Amifostine has been shown to protect against xerostomia induced by radiotherapy for head and neck cancer, but its impact on the therapeutic index is unknown. This is the first report focusing on amifostine related adverse effects leading to discontinuation of amifostine treatment. PATIENTS AND METHODS: Thirty-nine patients from two centers irradiated for head and neck cancer received i.v.-infusions of amifostine prior to each radiation fraction. In a phase III study, two daily amifostine doses, 200 mg/m(2) (n = 21) and 340 mg/m(2) (n = 18), were compared for protection against radiation induced toxicity. Total radiation dose was 60-70Gy (2Gy per fraction), nine patients received concurrent chemotherapy with cisplatin/5-FU. amifostine was usually discontinued after >1 episode of serious toxicity during subsequent treatment sessions. RESULTS: In 16/39 patients (41%) amifostine was discontinued due to severe adverse effects, which led to discontinuation of the phase III study. In four of 16 patients radiotherapy was delayed due to amifostine related adverse effects for 1-3 days. Discontinuation occurred more often in patients receiving chemotherapy. The results led to a literature review for amifostine treatment during radiotherapy in head and neck cancer patients. Regarding our series and published series using an amifostine schedule comparable to ours, total discontinuation rate was 27% (57/214). Discontinuation was significantly influenced by chemotherapy (P = 0.007) but not by amifostine dose (P = 0.156). CONCLUSION: Daily i.v. administration of amifostine during radiotherapy in head and neck cancer is associated with a high rate of serious adverse effects leading to discontinuation of amifostine treatment and sometimes delay of radiotherapy.

Is there a life-long risk of brachial plexopathy after radiotherapy of supraclavicular lymph nodes in breast cancer patients?

BACKGROUND AND PURPOSE: To contribute to the question whether the risk of radiation-related brachial plexopathy increases, remains constant or decreases with time after treatment. PATIENTS AND METHODS: Between 12/80 and 9/93, 140 breast cancer patients received supraclavicular lymph node irradiation using a telecobalt unit. Total dose was 60 with 3Gy per fraction at a depth of 0.5 cm and 52 with 2.6Gy per fraction to the brachial plexus at a depth of 3 cm. Twenty-eight women received chemotherapy, 34 tamoxifen. Brachial plexopathy was graded using a modified LENT-SOMA score. Actuarial complication-free survival and overall survival were obtained from Kaplan-Meier analysis. The impact of chemotherapy or tamoxifen was tested using the chi2 test. The annual incidence of radiation-related brachial plexopathy was assessed by exponential regression as described by Jung et al. [Radiother Oncol 61 (2001) 233]. RESULTS: Actuarial overall survival was 67.1% after 5 years, 54.0% after 10 years, 49.9% after 15 years, and 44.0% after 20 years. In 19/140 patients, brachial plexopathy grade>/=1 occurred after a median interval of 88 (30-217) months. The percentage of patients being free from plexopathy was 96.1% after 5 years, 75.5% after 10 years, 72.1% after 15 years, and 46.0% after 19 years, respectively. A significant impact of type of surgery, chemotherapy or tamoxifen was not observed. The annual incidence of brachial plexopathy was 2.9% for grade>/=1 lesions and 0.8% for grade>/=3 lesions. The rates did not change significantly with time. CONCLUSIONS: The risk of brachial plexopathy after supraclavicular lymph node irradiation in breast cancer patients remains constant for a considerable portion of the patient's life.

Individual radiosensitivity measured with lymphocytes may be used to predict the risk of fibrosis after radiotherapy for breast cancer.

BACKGROUND AND PURPOSE: To analyse the relationship of individual cellular radiosensitivity and fibrosis after breast conserving therapy. A new model was used describing the percentage of patients developing fibrosis per year and per patient at risk. PATIENTS AND METHODS: In a retrospective study, 86 patients were included, who had undergone breast conserving surgery and irradiation of the breast with a median dose of 55 Gy (54-55 Gy) given at 2.5 Gy/fraction (n=57) or 2 Gy/fraction (n=29). Median age was 62 years (range 44-86) and median follow-up was 7.5 years (range 5-17). Patients were examined for fibrosis according to the LENT/SOMA score. For analysis, fibrosis was classified as grade 0 and grade 1 (G0-1) or present grade 2 and grade 3 (G2-3). The time to complete development of fibrosis was determined by analysis of yearly mammograms. Individual cellular radiosensitivity was determined by scoring lethal chromosomal aberrations in in vitro irradiated (6 Gy) lymphocytes using metaphase technique. Patients with low/intermediate cellular radiosensitivity were compared with patients with high cellular radiosensitivity using actuarial methods. RESULTS: Ten patients developed fibrosis at 1-8 years after radiotherapy. Individual cellular radiosensitivity was described by normal distribution of lethal chromosomal aberrations, the average was 5.47 lethal aberrations per cell (standard deviation (SD) 0.71). Cellular radiosensitivity was defined as low/intermediate (< or =6.18 lethal aberrations) in 73 patients and high (>6.18 lethal aberrations; mean+SD) in 13 patients. In both groups, the actuarial rate of fibrosis-free patients decreased exponentially with time after radiotherapy. Patients with high cellular radiosensitivity showed a 2.3-fold higher annual rate for fibrosis than patients with intermediate and low radiosensitivity (3.6 versus 1.6% per year). CONCLUSIONS: In breast cancer patients, high individual cellular radiosensitivity as determined by the number of lethal chromosome aberrations in in vitro irradiated lymphocytes might be associated with an enhanced annual rate of fibrosis.

Indicators of late normal tissue response after radiotherapy for head and neck cancer: fibroblasts, lymphocytes, genetics, DNA repair, and chromosome aberrations.

PURPOSE: To investigate the relationship between late tissue response after radiotherapy, cellular sensitivity and DNA repair capacity measured in dermal fibroblasts and chromosomal aberrations measured in lymphocytes. The study was in particular designed to compare cellular parameters of patients with maximum differences in late tissue reactions. MATERIALS AND METHODS: The study was performed with 16 pair-wise matched head and neck cancer patients 2-7 years after curative therapy exhibiting maximum differences (grade 1 vs. grade 3) in late normal tissue reactions. Clinical endpoints were fibrosis, telangiectasia, mucositis and xerostomia using the radiation therapy oncology group score. Patients with grade 3 reactions were tested for mutations in ataxia telangiectasia (AT), Nijmegen Breakage Syndrome (NBS), MRE11, RAD50 and DNA ligase IV genes by means of polymerase chain reaction-single-strand conformation polymorphism and sequencing analysis. Skin fibroblasts obtained from biopsies were used to determine the cellular sensitivity by colony formation and the induction and repair of DNA double-strand breaks (dsb) using constant-field gel electrophoresis. Lymphocytes were taken to measure chromosomal damage either in metaphase using conventional chromosome analysis or in G(0) using premature chromosome condensation (PCC)-technique. RESULTS: Patients with extreme late reactions (grade 3) showed no evidence for an AT, NBS, MRE11 or RAD50 mutation. Studies with fibroblasts revealed that extreme late reactions were associated neither with a pronounced cellular radiosensitivity nor with a difference in dsb repair capacity. In contrast, there was a significant difference in chromosomal damage measured in lymphocytes. After in vitro irradiation with 6Gy, lymphocytes taken from overreacting patients showed on average a significantly higher number of lethal aberrations than lymphocytes isolated from patients with mild reactions (7.2+/-0.8 vs. 5.0+/-0.3). Similar differences were found for PCC fragments. CONCLUSION: This study suggests that lymphocytes are more promising than fibroblasts to predict patient's normal tissue response after radiotherapy.

Emergency localization of radioactive seeds lost during intracoronary brachytherapy.

Recently, it has been reported that brachytherapy catheters ruptured in vivo. Localization of lost beta-radiation-emitting seeds is a problem because no appropriate technique is available that is rapid and precise. We developed a technique to localize beta-emitting seeds utilizing the effect that beta-radiation induces bremsstrahlung. The loss of a single radioactive source was simulated in an Alderson Phantom representing a human body. The beta-induced bremsstrahlung could be detected selectively by a gamma-camera. The position of the radioactive seed could be located within 5 min with an accuracy of +/- 0.5 cm. The result of this study suggests that in an emergency case of loss of a brachytherapy source, a commercially available gamma-camera can be a valuable tool to detect lost beta-radiation-emitting seeds rapidly and precisely. In addition, the technique minimizes the patient's as well as the surgeon's exposure to radiation and reduces the extent of surgical trauma.

Evaluation of prognostic factors and two radiation techniques in patients treated with surgery followed by radio(chemo)therapy or definitive radio(chemo)therapy for locally advanced head-and-neck cancer.

BACKGROUND AND PURPOSE: Conventional radiotherapy (RT) still is the standard technique for head-and-neck cancer in many centers worldwide, whereas other centers replaced this technique by 3-D conformal RT, which is associated with more appropriate dose distributions. Comparative studies regarding outcome and toxicity are lacking. This study compared both techniques for overall survival (OS), metastases-free survival (MFS), loco-regional control (LC), and toxicity in stage III/IV head-and-neck cancer. PATIENTS AND METHODS: Data of 345 patients irradiated for stage III/IV squamous cell head-and-neck cancer were retrospectively analyzed. Patients received conventional RT (group A, n = 166) or 3-D conformal RT (group B, n = 179). Both techniques were compared for outcomes and toxicity. Eleven further potential prognostic factors were investigated: age, gender, performance status, tumor site, grading, T-stage, N-stage, AJCC-stage, chemotherapy, surgery, pre-RT hemoglobin. RESULTS: 3-year-OS was 62% in group A and 57% in group B (p = 0.15). 3-year-MFS was 67% and 76% (p = 0.46), 3-year-LC was 65% and 68%, respectively (p = 0.71). On multivariate analysis, gender (p = 0.005), performance status (p < 0.001), T-stage (p = 0.002), and N-stage (p < 0.001) were associated with OS. MFS was influenced by performance status (p < 0.001) and N-stage (p < 0.001), LC by gender (p = 0.021), T-stage (p < 0.001), and pre-RT hemoglobin level (>or= 12 better than < 12 g/dl, p = 0.004). Grade 2-3 xerostomia was less frequent with 3-D conformal RT (43% vs. 58%, p = 0.06). Otherwise, toxicities were similar. CONCLUSION: Both RT techniques resulted in similar treatment outcomes. Because xerostomia was less with 3-D conformal RT, this technique appeared beneficial for patients, in whom one parotid gland can be spared. Outcome was associated with gender, performance status, tumor stage, and pre-RT hemoglobin.