Hodgkin's lymphoma in elderly patients: a comprehensive retrospective analysis from the German Hodgkin's Study Group.

PURPOSE: With improved prognosis for patients with Hodgkin's lymphoma (HL), interest increasingly focuses on high-risk groups such as elderly patients. We thus performed a retrospective analysis using the German Hodgkin's Study Group (GHSG) database to determine clinical risk factors, course of treatment, and outcome in elderly HL patients in comparison with younger adults. PATIENTS AND METHODS: A total of 4,251 patients included in the GHSG studies HD5 to HD9 were analyzed, of whom 372 (8.8%) were 60 years or older and 3,879 (91.2%) were younger than 60 years. Patient characteristics, treatment results, toxicity, freedom from treatment failure (FFTF), and overall survival (OS) were compared. RESULTS: Elderly patients more often had mixed cellularity subtype, "B" symptoms, elevated erythrocyte sedimentation rate, and poorer performance status. Less frequently observed were nodular sclerosis subtype, large mediastinal mass, and bulky disease. Acute toxicity during chemotherapy was generally higher in elderly patients. This was most obvious for severe infections (grade 3 or 4; 15% v 6%) correlating with more severe leukopenia in elderly patients (grade 4; 38% v 23%). As a result, significantly fewer elderly patients received the intended full chemotherapy dose (75% v 91%). The survival analysis showed a significantly poorer treatment outcome for elderly patients in terms of 5-year OS (65% v 90%), FFTF (60% v 80%), and HL-specific FFTF (73% v 82%). CONCLUSION: Elderly patients have a poorer risk profile compared with younger HL patients and experience more severe treatment-associated toxicity. Higher mortality during treatment as well as lower dose-intensity are the major factors explaining the poorer overall outcome of elderly HL patients.

Involved-field radiotherapy is equally effective and less toxic compared with extended-field radiotherapy after four cycles of chemotherapy in patients with early-stage unfavorable Hodgkin's lymphoma: results of the HD8 trial of the German Hodgkin's Lymphoma Study Group.

PURPOSE: To investigate whether radiotherapy can be reduced without loss of efficacy from extended field (EF) to involved field (IF) after four cycles of chemotherapy. PATIENTS AND METHODS: Between 1993 and 1998, patients with newly diagnosed early-stage unfavorable HD were enrolled onto this multicenter study. Patients were randomly assigned to receive cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) + doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) for two cycles followed by radiotherapy of 30 Gy EF + 10 Gy to bulky disease (arm A) or 30 Gy IF + 10 Gy to bulky disease (arm B). RESULTS: Of 1,204 patients randomly assigned to treatment, 1,064 patients were informative and eligible for the arm comparison (532 patients in arm A; 532 patients in arm B). The median observation time was 54 months. Five years after random assignment, the overall survival (OSran) for all eligible patients was 91% and freedom from treatment failure (FFTFran) was 83%. Survival rates at 5 years after start of radiotherapy revealed no differences for arms A and B, respectively, in terms of FFTF (85.8% and 84.2%) and OS at 5 years (90.8% and 92.4%). There also were no differences between arms A and B, respectively, in terms of complete remission (98.5% and 97.2%), progressive disease (0.8% and 1.9%), relapse (6.4% and 7.7%), death (8.1% and 6.4%), and secondary neoplasia (4.5% and 2.8%). In contrast, acute side effects including leukopenia, thrombocytopenia, nausea, gastrointestinal toxicity, and pharyngeal toxicity were more frequent in the EF arm. CONCLUSION: Radiotherapy volume size reduction from EF to IF after COPP + ABVD chemotherapy for two cycles produces similar results and less toxicity in patients with early-stage unfavorable HD.

Biophysical analysis of the acute toxicity of radiotherapy in Hodgkin's lymphoma--a comparison between extended field and involved field radiotherapy based on the data of the German Hodgkin Study Group.

PURPOSE: To determine biophysical parameters from the complication probability data during and after radiotherapy of Hodgkin's lymphoma (HL), based on the number of gastrointestinal side effects that were found in the multicenter HD8 trial of the German Hodgkin Lymphoma Study Group. METHODS AND MATERIALS: Between 1993 and 1998, 1204 patients with newly diagnosed, histology-proven HL in clinical Stages I/IIA/IIB with defined risk factors and stage IIIA without risk factors were enrolled into the multicenter HD8 study. Patients were randomized to receive two cycles of COPP (cyclophosphamide, vincristine, procarbazine, prednisone) alternating with two cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) followed by radiotherapy (RT) of 30 Gy extended field plus 10 Gy to bulky disease (Arm A) or 30 Gy involved field plus 10 Gy to bulky disease (Arm B). For 910 patients, the rates of acute gastrointestinal side effects during and after RT could be determined. Comparison showed differences between Arms A and B (Grade 1-2: 16.6 vs. 3.9; Grade 3-4: 0.9 vs. 0.2; p < 0.001). From the dose-volume histograms for a "standard patient" (volume intestine 2300 cm3), we determined the normal tissue complication probability (NTCP) (V, D, m, n, TD50), the biophysical parameter TD50, and n (volume dependent) in such a manner that the observed NTCP in Arm A in cases of supradiaphragmatic involvement only and in cases of infradiaphragmatic involvement correlated with the calculated values. RESULTS: Of 1,204 patients randomized, 1,064 patients were informative for the comparison of study arms. The median observation time was 54 months. The overall survival for all eligible patients was 91%, and freedom from treatment failure was 83%. Survival rates at 5 years after start of RT revealed no differences in terms of freedom from treatment failure (85.8% in Arm A, 84.2% in Arm B) and overall survival (90.8% and 92.4%). There were also no differences between the two arms in terms of complete remission, progressive disease, relapse, death, and secondary neoplasias. In contrast, acute side effects, including leukopenia, thrombocytopenia, nausea, gastrointestinal toxicity, and pharyngeal toxicity, were more frequent in the extended field arm. Concerning gastrointestinal toxicity, the different radiation treatment volumes resulted in different NTCPs. On the basis of these findings, values of n = 0.09 and TD50 = 32 Gy were derived. However, this biophysical model is sensitive to variations of the parameters. A deviation of 1% of TD50 results in a deviation of 10% of the NTCP. CONCLUSION: Radiotherapy volume reduction from extended field to involved field after two cycles of COPP/ABVD chemotherapy gives similar results and less toxicity in patients with early-stage, unfavorable HL. Biophysical parameters could be determined from the complication probability data after RT of HL. Because of the exponential dependence, this biophysical model is unstable. It represents a "start model" until further data can be incorporated.

Three-year clinical follow-up after strontium-90/yttrium-90 beta-irradiation for the treatment of in-stent coronary restenosis.

Because late vessel failure has been speculated as a possible limitation of vascular brachytherapy, we conducted a prospective clinical evaluation at 6, 12, 24, and 36 months of follow-up after irradiation with strontium-90/yttrium-90 for in-stent restenosis, regardless of the patient's symptomatic status. We report complete 3-year follow-up data for 106 consecutive patients. The cumulative rate of death at 6, 12, 24, and 36 months was 0.9%, 0.9%, 0.9%, and 1.9% respectively. The corresponding rates for acute ST-elevation myocardial infarction were 2.8%, 4.7%, 4.7%, and 4.7%, respectively. The cumulative rate of late thrombotic occlusion at 6, 12, 24, and 36 months was 3.8%, 4.7%, 4.7%, and 4.7%, respectively. The corresponding rates of target lesion revascularization and target vessel revascularization were 8.5% and 12.3% (p = 0.046), 14.2% (p = 0.157) and 18.0% (p = 0.046), 12.3% and 18.9% (p = 0.008), and 21.7% (p = 0.083) and 29.2% (p = 0.005), respectively. The cumulative rate of all major adverse cardiovascular events at 6, 12, 24, and 36 months was 16.1%, 24.5% (p = 0.003), 27.4% (p = 0.083), and 35.8% (p = 0.003), respectively. In conclusion, these results indicate a delayed and, even in the third year after the index procedure, continued restenotic process after beta irradiation of in-stent restenotic lesions.

Chemoradiation for ductal pancreatic carcinoma: principles of combining chemotherapy with radiation, definition of target volume and radiation dose.

Review of the role of chemoradiotherapy in the treatment of locally advanced pancreatic cancer with a specific focus on the technical feasibility and the integration of chemoradiotherapy into multimodal treatment concepts. Combined chemoradiotherapy of pancreatic cancer is a safe treatment with an acceptable profile of side effects when applied with modern planning and radiation techniques as well as considering tissue tolerance. Conventionally fractionated radiation regimens with total doses of 45-50 Gy and small-volume boost radiation with 5.4 Gy have found the greatest acceptance. Locoregional lymphatic drainage should be included in the planning of target volumes because the risk of tumor involvement and local or loco-regional recurrence is high. Up to now, 5-fluorouracil has been considered the "standard" agent for concurrent chemoradiotherapy. The role of gemcitabine given concurrently with radiation has not yet been defined, since high local efficacy may also be accompanied by enhanced toxicities. In addition, no dose or administration form has been determined to be "standard" up to now. The focus of presently ongoing research is to define an effective and feasible regimen of concurrent chemoradiotherapy. While preliminary results indicate promising results using gemcitabine-based chemoradiotherapy, reliable data derived from mature phase III trials are greatly needed. Intensity-modulated radiotherapy has been developed to improve target-specific radiation and to reduce organ toxicity. Its clinical relevance still needs to be defined.

Concurrent chemoradiotherapy with gemcitabine and cisplatin after incomplete (R1) resection of locally advanced pancreatic carcinoma.

PURPOSE: To analyze, in a prospective clinical trial, the efficacy and toxicity of concurrent radiotherapy and chemotherapy with gemcitabine and cisplatin in patients with incompletely (R1) resected pancreatic cancer. METHODS AND MATERIALS: Between 2000 and 2002, a total of 30 pancreatic cancer patients were treated. Radiotherapy was performed in 15 patients up to a total dose of 45.0 Gy. An additional 15 patients received a total dose of 50.0 Gy according to the International Commission on Radiation Units and Measurements (ICRU) Report 50 reference point (equivalent to 45.0 Gy at the isodose, including 90% covering the former tumor area and local lymph nodes). Concurrent with radiotherapy, four applications of gemcitabine (300 mg/m(2)) and cisplatin (30 mg/m(2)) were administered. After chemoradiotherapy, patients received four additional courses of gemcitabine (1000 mg/m(2)) and cisplatin (50 mg/m(2)) on Days 1 and 15 in a 4-week cycle. RESULTS: The median progression-free survival was 10.6 months, and the median overall survival was 22.8 months. The 1-, 2-, and 3-year survival rate was 81%, 43%, and 26%, respectively. After completion of chemoradiotherapy, distant metastasis was observed in 14 patients during a median follow-up of 15.0 months (range, 4.6-30.0). One patient developed both local recurrence and distant metastases. Hematologic toxicities were the most prominent side effects (leukopenia Grade 3 and 4 in 53% and 7% and thrombocytopenia Grade 3 and 4 in 33% and 7% of patients, respectively). Grade 3 and 4 GI toxicity was not observed. CONCLUSION: Postoperative chemoradiotherapy with gemcitabine and cisplatin after incomplete (R1) resection of pancreatic carcinoma is safe and feasible. A prolonged progression-free survival suggests high local efficacy, translating into a benefit of overall survival. On the basis of the favorable outcome of patients receiving gemcitabine/cisplatin-based chemoradiotherapy, testing this combined treatment strategy appears warranted in a comparative trial.

Only sociodemographic variables predict quality of life after radiography in patients with head-and-neck cancer.

PURPOSE: Psychosocial factors influence patient compliance and have an effect on survival. Identifying patients at risk of decreased quality of life (QOL) with no extra expenditure in terms of hospital staff time or resources is mandatory to plan psychosocial support. METHODS AND MATERIALS: Between 1997 and 2000, 242 patients with head-and-neck cancer (30% pharyngeal, 29% oropharyngeal, and 13% laryngeal cancer) were screened. Of these, 28.5% refused to participate and 19.0% were excluded (Karnofsky performance score <50, language and cognitive deficits, death, or noncompliance). A total of 124 patients were assessed with the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire at ti1 (beginning of radiotherapy [RT]). Eighty-three patients from this group were examined, with complete data from ti1 to ti3 (6 weeks after RT). RESULTS: The QOL did not change during RT. In logistic regression analysis, medical information, in contrast to sociodemographic variables, turned out to have no influence on the ability to predict low QOL (sensitivity 80% vs. 32%). Four sociodemographic variables were entered in the regression model (children, currently employment, ethanol abuse, level of secondary education) and accounted for 26% of variance in QOL at ti3. CONCLUSION: By routinely obtaining clinical information from the patient's history, patients at risk of low QOL after RT can be identified and could benefit from early psychosocial support.

Evolution of angiographic restenosis rate and late lumen loss after intracoronary beta radiation for in-stent restenotic lesions.

The aim of this study was to investigate the time course of angiographic restenosis rate and late loss after successful percutaneous coronary intervention and vascular brachytherapy with beta-irradiation using strontium-90/yttrium-90 in 98 patients who were prospectively enrolled into a quantitative angiographic and clinical follow-up protocol at 6, 12, and 24 months after the index procedure, regardless of their symptom status. Actuarial restenosis rates measured 11.2 +/- 5% at 6 months of follow-up, 24.5 +/- 5% at 12 months, and 28.5 +/- 6% at 24 months, respectively. Late loss of the stent segment during the first 6 months measured 0.38 +/- 0.40 mm (6 to 12 months: 0.25 +/- 0.38 mm; 12 to 24 months: 0.16 +/- 0.32 mm), of the injured segment 0.27 +/- 0.21 mm (6 to 12 months: 0.21 +/- 0.26 mm; 12 to 24 months: 0.13 +/- 0.24 mm), of the irradiated segment 0.18 +/- 0.29 mm (6 to 12 months: 0.19 +/- 0.31 mm; 12 to 24 months: 0.11 +/- 0.27 mm), and of the analysis segment 0.18 +/- 0.36 mm (6 to 12 months: 0.17 +/- 0.29 mm; 12 to 24 months: 0.11 +/- 0.20 mm). Restenosis after angioplasty and beta-irradiation of in-stent restenotic lesions is not complete within 6 months but is sustained with a gradual decrease over 24 months.

Impact of barotrauma on acute and late angiographic and clinical outcomes following angioplasty and beta-irradiation of coronary in-stent restenotic lesions.

INTRODUCTION: The aim of this study was to prospectively evaluate the impact of different degrees of vessel barotrauma on the acute and 1-year clinical and angiographic outcomes of percutaneous coronary intervention (PCI) and adjunctive vascular brachytherapy (VBT) with 90Sr/90Y for in-stent restenotic lesions (ISR) in 118 patients. METHODS AND RESULTS: Sixty consecutive patients were treated according to an aggressive PCI strategy (group 1); fifty-eight were treated non-aggressively (group 2). Irradiation was performed with a manual afterloader. Clinical and angiographic baseline characteristics did not differ between groups. Group 1 yielded a higher acute lumen gain (2.3 +/- 1.2 mm versus 1.7 +/- 1.3 mm; p=0.005) and a higher prevalence of additional stent implantation (48.3% versus 22.4%; p=0.003). At follow-up, net gain (1.8 +/- 0.7 mm versus 1.4 +/- 0.8 mm; p=0.102) was equalized by a higher late loss in group 1 (0.6 +/- 0.8 mm versus 0.3 +/- 0.7 mm; p=0.036). Remaining target vessel late loss, due to edge effects, was considerably higher in group 1 than in group 2 (0.5 +/- 0.8 mm versus 0.2 +/- 0.5 mm; p<0.001), leading to a higher rate of binary angiographic restenosis (23.3% versus 6.9%; p=0.013) and target vessel revascularization (16.7% versus 5.2%; p=0.046). After excluding patients who received additional stents, the angiographic differences between groups were attenuated. CONCLUSION: Our study does not support the use of oversized balloons and high inflation pressures for the treatment of ISR when combined with VBT. Additional stent implantation combined with VBT carries a high risk of repeat revascularization in the setting of ISR and should be avoided.

Radiation therapy combined with photofrin or 5-ALA: effect on Lewis sarcoma tumor lines implanted in mice. Preliminary results.

AIMS AND BACKGROUND: Ionizing irradiation is a well-established therapeutic modality for cancer. Photodynamic therapy (PDT), especially with 5-ALA and Photofrin, is highly effective in some tumor types. Chemical modifiers, so-called radiosensitizers, are used in order to increase the efficacy of radiotherapy. Most of the known and routinely used radiosensitizers are not tumor selective, so that the normal tissue reaction toxicity is also increased. In the present study we investigated whether a porphyrin derivative that is currently used as a tumor-photosensitizing agent in photodynamic therapy (PDT) may also act as a tumor-specific radiosensitizer. MATERIALS AND METHODS: For our investigation we used Balb/c mice implanted with Lewis sarcoma and irradiated with 3 Gy combined with injection of 5-ALA or Photofrin at various concentrations before irradiation. RESULTS: 5-ALA had no effect as a radiosensitizer at any of the concentrations examined. Photofrin at a concentration of 5 mg/kg proved to be a chemical modifier of ionizing radiation, delaying tumor growth and reducing the overall tumor volume by about 50% after six days. CONCLUSION: Photofrin has marked efficacy as a radiosensitizer and can be used in the future as a selective tumor radiosensitizer.

Optimized radiation of pelvic volumes in the clinical setting by using a novel bellyboard with integrated gonadal shielding.

The purpose of this study was to determine the feasibility of a custom-made, modified bellyboard to reduce radiotherapy side effects on small bowel, bladder, skin, and male gonads. Two groups of 10 consecutive patients each were treated from January 2003 through April 2003 with neoadjuvant (45 Gy) or adjuvant (54 Gy) radio(chemo)therapy in single fractions of 5 days a week 1.8 Gy for rectal carcinoma, using a photon energy of 15 MV. One group was positioned in a prone position without an immobilization device, the other group was positioned on our bellyboard. Treatment planning was calculated by using a 4- and a 3-field box technique. Differences in the dose of organs of risk were calculated. For 1 male patient, a gonadal shielding was developed and integrated. All patients examined with the bellyboard demonstrated an anterior and cranial dislocation of the small bowel. Using a 4-field box, the mean dose to the small bowel of patients treated on our bellyboard was 56.5% as compared to 63.1% when treated without the bellyboard. When a 3-field box was used, the mean dose to the small bowel was 52.4% when the bellyboard was used, as compared to a mean dose of 63.1% without the bellyboard. Regarding the dose volume effects to the bladder, the mean dose for patients treated with a 4-field box was about 14.5% higher as compared to patients treated with a 3-field box. The mean dose to the hip joints and skin also depended on the radiation technique. The patient who received gonadal shielding received a maximal total gonadal dose of about 75.0 cGy in single fractions of maximal 3.0 cGy (TL-dosimeters). Daily setup variations evaluated by a beam's-eye view were similar in both groups and ranged from 0.5 cm 1.0 cm. For daily use, our bellyboard appears to be an ideal compromise due to effectiveness, its easy handling, and reproductive positioning; moreover, it can also be used in combination with gonadal shielding.

Two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine plus extended-field radiotherapy is superior to radiotherapy alone in early favorable Hodgkin's lymphoma: final results of the GHSG HD7 trial.

PURPOSE: To investigate whether combined-modality treatment (CMT) with two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by extended-field radiotherapy (EF-RT) is superior to EF-RT alone in patients with early favorable Hodgkin's lymphoma (HL). PATIENTS AND METHODS: Between 1993 and 1998, 650 patients with newly diagnosed, histology-proven HL in clinical stages IA to IIB without risk factors were enrolled onto this multicenter study and randomly assigned to receive 30 Gy EF-RT plus 10 Gy to the involved field (arm A) or two cycles of ABVD followed by the same radiotherapy (arm B). Results At a median observation time of 87 months, there was no difference between treatment arms in terms of complete response rate (arm A, 95%; arm B, 94%) and overall survival (at 7 years: arm A, 92%; arm B, 94%; P = .43). However, freedom from treatment failure was significantly different, with 7-year rates of 67% in arm A (95% CI, 61% to 73%) and 88% in arm B (95% CI, 84% to 92%; P

Feasibility of photofrin II as a radiosensitizing agent in solid tumors--preliminary results.

BACKGROUND: Photofrin II has been demonstrated to serve as a specific and selective radiosensitizing agent in in vitro and in vivo tumor models. We aimed to investigate the feasibility of a clinical application of Photofrin II. MATERIAL AND METHODS: 12 patients were included in the study (7 unresectable solid tumors of the pelvic region, 3 malignant gliomas, 1 recurrent oropharyngeal cancer, 1 recurrent adenocarcinoma of the sphenoid sinus). The dose of ionizing irradiation was 30-50.4 Gy; a boost irradiation of 14 Gy was added for the pelvic region. All patients were intravenously injected with 1 mg/kg Photofrin II 24 h prior to the commencement of radiotherapy. Magnetic resonance imaging (MRI) controls and in some cases positron emission tomography (PET) were performed in short intervals. The mean follow-up was 12.9 months. RESULTS: No major adverse events were noted. Minor adverse events consisted of mild diarrhea, nausea and skin reactions. A complete remission was observed in 4/12 patients. A reduction in local tumor volume of >45% was achieved in 4/12 patients. Stable disease was observed in 4/12 patients. 1 patient showed local disease progression after 5 months. CONCLUSION: The early follow- up results are encouraging regarding the feasibility of the application of Photofrin II as a radiosensitizing agent.

A new concurrent chemotherapy with vinorelbine and mitomycin C in combination with radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck.

OBJECTIVE: The purpose of this pilot study was to evaluate the feasibility and toxicity of concurrent chemotherapy with vinorelbine and mitomycin C in combination with accelerated radiotherapy (RT) in patients with locally advanced cancer of the head and neck. PATIENTS AND METHODS: Between January 2003 and March 2004, 15 patients with T4/N2-3 squamous cell carcinoma (12/15) and with N3 cervical lymph node metastases of carcinoma of unknown primary (3/15) were treated with chemotherapy and simultaneous accelerated RT. RESULTS: 11 patients completed therapy without interruption or dose reduction. Grade 3-4 acute mucosal toxicity was observed in 9/15 patients, grade 4 hematologic toxicity in 6/15 patients. At a median follow-up of 7.5 months, 2 patients have died of intercurrent disease, 2 patients have experienced local relapse; 5 patients are alive with no evidence of disease at the primary tumor site. DISCUSSION: The described regimen is highly effective, but led to remarkable side effects.

Psychosocial stress in cancer patients during and after radiotherapy.

BACKGROUND AND PURPOSE: The aim of this study was to investigate stress in tumor patients by means of a cancer-specific questionnaire in the course of radiotherapy. MATERIAL AND METHODS: Disease-specific aspects of psychosocial stress (Herschbach's Questionnaire on Stress in Cancer Patients, QSC) were self-assessed by patients with different tumor types before radiotherapy (ti1), after radiotherapy (ti2), and 6 weeks after the end of radiotherapy (ti3). We investigated 265 of 446 patients (157 male, 108 female; median age 58.6 years) with complete data of ti1-ti3. RESULTS: In the course of investigation, the most prominent stress scale of the patients proved to be physical efficiency, without significant changes during treatment and after therapy. Significant increases in stress were observed for anxiety, pain, and information at ti3 (p < 0.001, p = 0.001, p = 0.035). Women showed significantly higher stress from ti1 to ti3, younger patients displayed a decrease in anxiety, whereas elderly patients demonstrated an increase (p = 0.016). Breast cancer patients had the highest stress levels. The probability of correctly predicting increase in stress (sensitivity) was 78% and the specificity 67%. The relevant predictor variables were tumor stage, addiction to alcohol or nicotine, metabolic disorder, marital status, and age. CONCLUSION: Patients who experienced stress at the beginning of radiotherapy also had the same or increased levels of stress during and shortly after treatment and needed permanent psychosocial support to improve quality of life. The identification of patients with high stress levels at the beginning of therapy could be helpful.

Adaptive doses of irradiation-an approach to a new therapy concept for bladder cancer?

Radiation adaptive response in terms of induced radioresistance or hyperradiosensitivity, has been studied in HCV29 (human bladder epithelium) and RT4 (human bladder carcinoma) cell lines. After pre-irradiation doses of 0.05 Gy or 0.1 Gy, HCV29 cells showed induced radioresistance, whereas after pre-irradiation doses of 0.05 Gy, 0.1 Gy, 0.2 Gy, and 0.5 Gy, the RT4 cells clearly showed hyperradiosensitivity. On the basis of these results, an approach has been developed that may lead to a concept for a new radiotherapeutic regimen of bladder cancer that includes protection of normal cells, on the one hand, and the potential of tumor cell damage, on the other hand. These findings need to be confirmed in further studies for the benefit of the patients.

Prognostic implications of hemoglobin levels before and after surgery as well as before and after radiochemotherapy for head and neck tumors.

Several studies have shown that tumor cells may develop resistance to radiotherapy, proliferating under hypoxic conditions. Following surgery, patients may develop low hemoglobin levels, which may cause low oxygen conditions. This retrospective analysis was undertaken to determine the impact of low hemoglobin levels in patients with head and neck tumors treated with combined-modality therapy (surgery and postoperative radiochemotherapy). We studied 120 patients with mostly advanced head and neck tumors (88% stage III/IV) who had undergone macroscopically complete resections of their primary tumors and lymph node metastases. At 20-277 days after surgery (median: 51.3 days), these patients received postoperative chemoradiotherapy (56.7 Gy of radiation over 28-49 days and cisplatin 6 mg/m(2) body surface area on radiation treatment days with a cumulative dose of 96 mg/m(2)). Normal hemoglobin levels were considered to be 12 g/dl for females and 13 g/dl for males. Decreased hemoglobin levels before or after surgery and before or after chemoradiotherapy were correlated with the prognosis. Preoperatively, 99 of 114 patients (87%) had normal levels of hemoglobin compared with only 20 of 107 patients (19%) postoperatively. At the onset of radiochemotherapy, the hemoglobin levels of 82 of 116 patients (71%) were within the normal range. After radiochemotherapy, however, 62 of 114 patients (54%) had normal hemoglobin levels. Univariate analysis (Kaplan-Meier method and log-rank test) showed that patients with decreased pre- or postoperative hemoglobin levels had significantly worse locoregional control ( P=0.032 and P=0.0001, respectively) and lower overall survival ( P=0.0013 and P=0.0002, respectively) than patients with normal hemoglobin levels. The 3-year locoregional control rates in patients with preoperative hemoglobin levels that were normal, were reduced by 1-2 g/dl or were reduced by more than 3 g/dl, respectively, were 78%, 55% and 50%. Correlated with normal and diminished postoperative hemoglobin levels, the 3-year locoregional control rates were 90%, 84% and 50%, respectively. There was no correlation between prognosis and hemoglobin level at the onset or after radiochemotherapy. On multivariate analysis, only the postoperative hemoglobin level remained a prognostic factor for locoregional control ( P=0.0241) and overall survival ( P=0.0080). We conclude that low postoperative hemoglobin levels resulting from blood loss may influence the efficacy of postoperative radiochemotherapy in patients with head and neck cancer. Early intervention to raise the postoperative hemoglobin level may result in better tumor control and overall survival after combined-modality therapy.

[Psychometric properties of the Stress Index RadioOncology (SIRO)--a new questionnaire measuring quality of life of cancer patients during radiotherapy]. / Psychometrische Eigenschaften des Stress Index RadioOnkologie (SIRO)--ein neuer Fragebogen zur Erfassung der Lebensqualität bei Patienten unter Strahlentherapie.

PURPOSE: In the course of radiotherapy oncological patients often experience considerable psychosocial distress. For its measurement however, no specific questionnaire is available. The Stress Index RadioOncology (SIRO), which is based upon the results of extensive preliminary studies, will be made available as a screening-instrument to facilitate measurement of psychosocial distress of cancer patients, including radiotherapy-induced distress. The aim of this study is, to psychometrically evaluate the preliminary version of the questionnaire, to transfer it to the final version (SIRO) and to gain information about the psychosocial distress of radiooncological patients at the beginning of radiotherapy. PATIENTS AND METHODS: 104 cancer patients (18 to 85 years) with different diagnoses have been included in the study (Table 1). The data have been assessed by means of the preliminary version of the new questionnaire SIRO, the HADS, EORTC QLQ-C30 and LS. With 25 patients semistructured clinical interviews have been conducted. RESULTS: The requirements for reliability (Table 3) and validity (Table 4) of the SIRO have either been fulfilled or exceeded. The highest distress value has been found in the scale "Psycho-physical Distress", followed by the scale "Partnership Problems", "Radiotherapeutical Distress", and "Information Deficits" (Figure 1). On the item level, the highest distress was experienced due to reduction of efficiency and anxiety (Table 2). With regard to the radiotherapy items, patients were most distressed by fears of possible side effects and by the fact of being irradiated. Patients with palliative treatment option were higher distressed than those with curative treatment (Table 5). CONCLUSIONS: The preliminary version of the new self-report questionnaire (SIRO) has proven to be valid, reliable and practicable, and can therefore be taken unchanged to measure the psychosocial distress of radiooncological patients.