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.

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.

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.

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.

Prognostic factors for local control and survival after radiotherapy of metastatic spinal cord compression.

PURPOSE: To evaluate potential prognostic factors for local control and survival after radiotherapy of metastatic spinal cord compression (MSCC). PATIENTS AND METHODS: The following potential prognostic factors were investigated retrospectively in 1,852 patients irradiated for MSCC: age, sex, performance status, primary tumor, interval between tumor diagnosis and MSCC (< or = 15 v > 15 months), number of involved vertebrae (one to two v > or = three), other bone metastases, visceral metastases, pretreatment ambulatory status, time of developing motor deficits before radiotherapy (faster, 1 to 14 v slower, > 14 days), and radiation schedule (short-course v long-course radiotherapy). RESULTS: On univariate analysis, improved local control of MSCC was associated significantly with favorable histology (breast cancer, prostate cancer, lymphoma/myeloma), no visceral metastases, and long-course radiotherapy. On multivariate analysis, absence of visceral metastases and radiation schedule maintained significance. On univariate analysis, improved survival was associated significantly with female sex, favorable histology, no visceral or other bone metastases, good performance status, being ambulatory before radiotherapy, longer interval between tumor diagnosis and MSCC, and slower development of motor deficits before radiotherapy. Long-course radiotherapy showed a trend. On multivariate analysis, histology, visceral metastases, other bone metastases, ambulatory status before radiotherapy, interval between tumor diagnosis and MSCC, and time of developing motor deficits maintained significance. CONCLUSION: Poorer local control after radiotherapy for MSCC is associated with visceral metastases and short-course radiotherapy. Long-course radiotherapy seems preferable for patients with more favorable prognoses, given that these patients may live long enough to develop MSCC recurrences. Long-term survival after radiotherapy for MSCC may be predicted if several prognostic factors are considered.

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.

Hyperfractionated-accelerated radiotherapy followed by radical surgery in locally advanced tumors of the oral cavity.

PURPOSE: To evaluate the outcome of hyperfractionated-accelerated radiotherapy and subsequent planned primary tumor resection and radical neck dissection in locally advanced tumors of the oral cavity. PATIENTS AND METHODS: This retrospective analysis evaluates 126 subsequent patients who were treated between 1988 and 1997 for locally advanced tumors of the oral cavity (with extension into the oropharynx in 17 patients), 34 (27%) AJCC stage III and 92 (73%) stage IV. Primary tumor and nodal metastases were irradiated with 1.4 Gy bid to a median total dose of 72.8 Gy (range 58.8-75.6 Gy). Then, planned radical surgery of the primary site according to the initial tumor extent and cervical nodes was performed. Median follow-up of living patients was 6 years (range 1-11 years). RESULTS: 4 weeks after radiotherapy, 14 patients (11%) had complete tumor remission, 92 (73%) partial remission, 15 (12%) no change, and five (4%) progressive disease. Complete resection was achieved in 117 (93%) patients (nine incomplete resections). 5-year locoregional control rate was 62 +/- 9%, overall survival 36 +/- 9%. Surgery-related morbidity occurred in 42 patients (33%; mainly delayed wound healing and fistulae), overall severe treatment-related morbidity in 46 patients (36%). 24/84 relapse-free patients (29%) required a percutaneous gastrostomy or nasal tube > or = 1 year after therapy. CONCLUSION: In this study, the outcome of combined curative radiotherapy and planned surgery of the primary tumor and neck nodes was comparable to reported results of hyperfractionated radiotherapy with or without salvage surgery of the neck nodes with respect to locoregional control and overall survival. Planned surgery carries a substantial risk of morbidity and seems to offer no benefit in comparison to salvage surgery of the neck nodes only. Therefore, salvage surgery is preferred.

Late effects and cosmetic results of conventional versus hypofractionated irradiation in breast-conserving therapy.

BACKGROUND AND PURPOSE: Breast irradiation after lumpectomy is an integral component of breast-conserving therapy (BCT). As the prognosis is general good following BCT, late morbidity and cosmesis are important. The present study compares two different radiation schedules with respect to these two endpoints. PATIENTS AND METHODS: 129 breast cancer patients (pT1-2 pN0-1 cM0) were irradiated between 09/1992 and 08/1994 with either a 22-day fractionation schedule (2.5 Gy to 55 Gy, 4x/week, n = 65) or with a conventional fractionation schedule (28 days, 2.0 Gy to 55 Gy, 5x/week, n = 64), both without additional boost. The equivalent dose of 2-Gy fractions (EQD2) was 55 Gy and 62 Gy, respectively. Late toxicity, assessed according to the LENT-SOMA criteria, and cosmetic outcome, graded on a 5-point scale, were evaluated after a median of 86 months (range 72-94 months) in tumor-free breast cancer patients. RESULTS: LENT-SOMA grade 2/3 toxicity (2.5 Gy vs. 2.0 Gy): breast pain (18% vs. 11%; p = 0.3), fibrosis (57% vs. 16%; p < 0.001), telangiectasia (22% vs. 3%; p = 0.002), atrophy (31% vs. 3%; p < 0.001). Medication to breast pain was taken by 8% versus 9% of patients. Cosmesis was very good/good/acceptable in 75% versus 93% (2.5 Gy vs. 2.0 Gy; p = 0.006). CONCLUSION: Late morbidity was significantly frequent and cosmesis was significantly worse after hypofractionated radiotherapy (2.5 Gy to 55 Gy). However, morbidity was not associated with major implications on daily life.

[Effectiveness and toxicity of reirradiation (Re-RT) for metastatic spinal cord compression (MSCC)]. / Effektivität und Toxizität einer Re-Bestrahlung (Re-RT) bei metastatisch bedingter Rückenmarkkompression (MBRK).

BACKGROUND AND PURPOSE: Radiation myelopathy is a serious late toxicity after radiotherapy (RT) of metastatic spinal cord compression (MSCC). The risk of myelopathy depends on the equivalent dose in 2-Gy fractions (EQD2). Many radiation oncologists are concerned about spinal Re-RT, because it may result in a high cumulative EQD2. This study investigates effectiveness and feasibility of Re-RT for in-field recurrence of MSCC. PATIENTS AND METHODS: 74 patients, irradiated between 01/1995 and 12/2003 for MSCC, were reirradiated for in-field recurrence of MSCC (Table 1). Primary RT was performed with 1 x 8 Gy (n = 34), 5 x 4 Gy (n = 28), 10 x 3 Gy (n = 4), 15 x 2.5 Gy (n = 4), or 20 x 2 Gy (n = 4). Recurrence occurred after median 6 months (2-40 months). Re-RT was performed with 1 x 8 Gy (n = 35), 5 x 3 Gy (n = 16), 5 x 4 Gy (n = 13), 10 x 2 Gy (n = 4), 12 x 2 Gy (n = 3), or 17 x 1.8 Gy (n = 3). Cumulative EQD2 (alpha/beta = 2 Gy) was 39-40 Gy (n = 21), 49-50 Gy (n = 41), 56-60 Gy (n = 6), or > 60 Gy (n = 6). Follow-up after Re-RT was median 9 months (2-52 months). RESULTS: Re-RT led to an improvement of motor function in 29/74 patients (39%; Figures 1 to 3). On multivariate analysis, outcome was significantly influenced by type of primary tumor (p = 0.013) and by the time of developing motor deficits before Re-RT (p = 0.037), but not by radiation schedule (p = 0.560), by ambulatory status before Re-RT (p = 0.471), by cumulative EQD2 (p = 0.795), nor by the interval between primary RT and Re-RT (p = 0.420; Table 2). Radiation myelopathy was not observed in the whole series. CONCLUSION: Re-RT is an effective treatment for an in-field recurrence of MSCC. After a cumulative EQD2 < or = 50 Gy, radiation myelopathy appears unlikely.

Results of three dimensional conformal radiotherapy and hormonal therapy for local recurrence after radical prostatectomy.

BACKGROUND AND PURPOSE: Analysis of treatment results of combined three-dimensional conformal radiotherapy (3DCRT) and hormonal therapy in patients with locally recurrent prostate cancer after radical prostatectomy. PATIENTS AND METHODS: Between 1992 and 1998, 24 patients presented with a rising prostate-specific antigen (PSA) between 4 and 152 months following radical prostatectomy and a local recurrence demonstrated by imaging. Recurrence was biopsy-proven in 13 cases. All patients were treated with 3DCRT to a total dose of 60-70 Gy. 21 patients (88%) received adjuvant hormone therapy up to a maximum of 6 months. RESULTS: All patients showed a response in PSA values after therapy. Median follow-up is 43 months. Overall survival is 80% and 67% at 3 and 5 years, respectively. Biochemical control rates are 53% and 38% at 3 and 5 years, respectively. 14 patients developed a second PSA relapse. Acute and late toxicities, classified with the RTOG score, were moderate. CONCLUSION: Radiotherapy and short-term adjuvant hormone therapy represent an effective and well-tolerated treatment for locally recurrent prostate cancer after radical prostatectomy resulting in good local control. Long-term prognosis in terms of biochemical control and disease-specific survival remains poor.

Is grading of breast fibrosis with mammography feasible?

PURPOSE: To establish a grading system for mammographic fibrosis and correlate it with clinical fibrosis. PATIENTS AND METHODS: Analogous to the LENT/SOMA scale a four-tiered scoring scale of breast fibrosis in mammography (G0 = absent, G1 = barely increased density, G2 = definitely increased density to G3 = very marked density) was established by two observers in a group of 16 patients. Reference mammograms were selected. Independently and blinded to clinical results, three observers scored the fibrosis in mammograms of further 31 patients examined by one radiation oncologist in a cross-sectional follow-up study. Pretreatment parenchyma density was judged according to the American College of Radiology (ACR). Interobserver correlation of mammography scoring as well as correlation of mammography and clinical findings were calculated with Cohen's weighted kappa. All patients had breast-conserving surgery and axillary resection for breast carcinoma T1-2N0-1. The breast was irradiated to a median reference dose of 55 Gy (range 50-60 Gy) with 2 Gy five times weekly or 2.5 Gy four times weekly. Two patients received chemotherapy, 14 patients tamoxifen. Median age was 55 years, median follow-up 8 years (4-15 years). RESULTS: 14 of 31 patients had clinical fibrosis, twelve G1 and two G2. In mammography, mild fibrosis (G1) was seen in 12/12/18 patients (observer 1/2/3) and moderate fibrosis (G2) in 9/10/2 patients. Interobserver correlation for observers 1 and 2 who had developed the score was fair (Cohen's weighted kappa 0.64, 95% confidence interval 0.4-0.88). However, it was weak for observer 3 (0.36 and 0.42, respectively) who relied on reference mammograms only. Independent interobserver correlation of pretreatment breast density was good for all observers (Cohen's weighted kappa 0.73-0.8). The correlation of fibrosis by mammography and palpation was weak (Cohen's weighted kappa 0.32-0.42). CONCLUSION: Grading fibrosis as depicted by mammography is possible, especially if observers prepare by jointly analyzing a training group. It may be useful to study treatment effects, e. g., of fractionation or drugs, because retrospective and repeated analysis is possible. The correlation of mammography with clinical grading should be further evaluated with more objective clinical reference tools.

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.

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.

Prognostic factors in the nonsurgical treatment of esophageal carcinoma with radiotherapy or radiochemotherapy: the importance of pretreatment hemoglobin levels.

BACKGROUND: The current study was performed to evaluate prognostic factors for overall survival (OS), distant metastasis (DM), and local failure (LF) in patients with Stage II/III esophageal carcinoma. METHODS: The following potential prognostic factors were retrospectively investigated in 124 patients treated with radiotherapy (RT) alone or with radiochemotherapy: age, gender, performance status, tumor location, tumor length, histology, histologic grade, T classification, N classification, International Union Against Cancer stage, chemotherapy, RT dose, and pre-RT hemoglobin level. RESULTS: Using univariate analysis (Kaplan-Meier method), pre-RT hemoglobin level, RT dose, tumor length, chemotherapy, and performance status were significantly associated with OS. Hemoglobin levels of 12.1-14.0 g/dL were associated with the best OS, followed by >/= 14.1 g/dL and /= 14 g/dL and

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.

Reducing the overall treatment time for radiotherapy of metastatic spinal cord compression (MSCC): 3-year results of a prospective observational multi-center study.

BACKGROUND: This prospective multi-center study investigates a reduction of the overall treatment time for radiotherapy of MSCC, which is important for these mostly disabled patients. PATIENTS AND METHODS: Two standard fractionation schedules, 30 Gy/10 fractions/2 weeks (n = 71) and 40 Gy/20 fractions/4 weeks (n = 65) were compared for functional outcome and ambulatory status. Motor function was graded using an 8-point-scale before RT, at the end and at 6, 12 and 24 weeks after RT. A multi-variate analysis was performed for functional outcome. Included variables were the fractionation schedule and the three relevant prognostic factors. These factors are the type of primary tumor, the time of developing motor deficits before RT and the pre-treatment ambulatory status. RESULTS: The ambulatory rates were 49% in the 30 Gy group and 52% in the 40 Gy group before RT (P = 0.888), and 56% and 60% after RT (P = 0.888). Improvement of motor function occurred in 45% of the 30 Gy group and 40% of the 40 Gy group (P = 0.752). The relevant prognostic factors were comparably distributed in both groups. According to the multivariate analysis, a slower development of motor deficits (P < 0.001), a favorable histology (P = 0.040) and being ambulatory (P = 0.045) were associated with better functional outcome, whereas the fractionation schedule had no significant impact (P = 0.311). CONCLUSIONS: The data suggest both schedules to be comparably effective for functional outcome. Thus, 30 Gy/10 fractions/2 weeks should be applied instead of 40 Gy/20 fractions/4 weeks. The reduction of the overall treatment time from 4 to 2 weeks means less discomfort for the paraparetic or paraplegic patient.

A prospective evaluation of two radiotherapy schedules with 10 versus 20 fractions for the treatment of metastatic spinal cord compression: final results of a multicenter study.

BACKGROUND: The optimal treatment of patients with metastatic spinal cord compression (MSCC) is still being debated. The current observational multicenter study, performed prospectively by the authors, evaluated two radiotherapy (RT) schedules and prognostic factors with respect to functional outcome METHODS: In the current study, 214 patients with MSCC were irradiated between April 2000 and September 2003 with 30 gray (Gy) per 10 fractions per 2 weeks (n = 110) or with 40 Gy per 20 fractions per 4 weeks (n = 104). Motor function and ambulatory status were evaluated before RT and until 6 months after RT. The following potential prognostic factors were investigated: RT schedule, performance status, age, number of irradiated vertebrae, type of primary tumor, pretreatment ambulatory status, and length of time developing motor deficits before RT. RESULTS: Both groups were balanced for patient characteristics and potential prognostic factors. Motor function improved in 43% of patients after 30 Gy and in 41% of patients after 40 Gy (P = 0.799). Posttreatment ambulatory rates were 60% and 64% (P = 0.708), respectively. A multivariate analysis demonstrated that a slower progression of motor deficits before RT (P < 0.001), a favorable histology of the primary tumor (P < 0.001), and being ambulatory before RT (P = 0.035) were associated with a better functional outcome. RT schedule (P = 0.269) and other variables had no significant impact. Acute toxicity was mild, and late toxicity was not observed during the period of follow-up. Follow-up was 12 (6-28) months in patients surviving >/= 6 months. CONCLUSIONS: Thirty gray per 10 fractions was preferable to 40 Gy per 20 fractions, because it was associated with similar outcome, less treatment time, and lower costs. The type of tumor, pretreatment ambulatory status, and length of time developing motor deficits before RT were relevant prognostic factors and should be considered in future studies.

Radiation-induced plexopathy and fibrosis. Is magnetic resonance imaging the adequate diagnostic tool?

PURPOSE: To investigate magnetic resonance imaging (MRI) features of radiation-induced plexopathy (RIP) and radiation-induced fibrosis frequently associated with RIP. PATIENTS AND METHODS: Seven patients with late radiation sequelae in the supraclavicular region were examined with MRI after a median interval of 7 years (range, 5-18 years) following radiotherapy and 4-7 years after the onset of RIP. Four patients had RIP plus severe soft-tissue fibrosis, two RIP without soft-tissue fibrosis (n = 2/6), and one patient fibrosis without RIP. Patients underwent surgery of breast cancer (n = 6) or chest wall relapse (n = 1) and radiotherapy to the supraclavicular fossa with cobalt with an anterior portal in fractions of 1.7-2.6 Gy to 43-51.6 Gy in 3 cm depth. All patients were relapse-free at the time of MRI. Fibrosis and RIP were scored clinically (RTOG classification). Fibrosis of the supraclavicular and/or axillary region was marked in three and mild in two patients. RIP was mild, marked and severe in two patients each. MRI was performed with a 1.5-T unit including coronal STIR, coronal and transversal T2-weighted, transversal T1-weighted and fat-saturated post-contrast (gadolinium-DTPA) spin echo sequences. RESULTS: The brachial plexus appeared normal in all patients, but subtle changes of adjoining tissue (slight, linear signal intensity in T2-weighted images or contrast enhancement surrounding the plexus) were detected in patients with RIP (n = 4/6) and the patient without RIP (n = 1). However, alterations of the soft tissue (marked signal intensity in T2-weighted sequences) correlated well with the clinical degree of fibrosis and were restricted to areas of marked to severe fibrosis (n = 3/3). CONCLUSION: Reliable MRI signs of RIP could not be identified. The severity of fibrosis closely corresponded to MRI features. The role of MRI in the diagnostic work-up of RIP is, therefore, the exclusion of tumor relapse.

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.