Fatigue, serum cytokine levels, and blood cell counts during radiotherapy of patients with breast cancer.

PURPOSE: To assess the level of fatigue during the course of adjuvant radiotherapy (RT) of breast cancer patients and its relation to anxiety, depression, serum cytokines, and blood count levels. METHODS AND MATERIALS: Forty-one patients who received adjuvant RT after breast-conserving surgery were prospectively studied. All patients underwent RT without concomitant chemotherapy. Patients rated their fatigue with two standardized self-assessment instruments, the Fatigue Assessment Questionnaire and a visual analog scale on fatigue intensity, before RT, during weeks 1-5 of RT, and 2 months after RT completion. In addition, the anxiety and depression levels were assessed with the Hospital Anxiety and Depression Scale. A differential blood cell count and the serum levels of the cytokines interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha were determined in parallel to the fatigue assessments. RESULTS: Fatigue intensity as assessed with the visual analog scale increased (p <0.001) until treatment week 4 and remained elevated until week 5. Two months after RT, the values had fallen to the pretreatment levels. Fatigue measured with the Fatigue Assessment Questionnaire did not increase significantly during treatment, but the subscores on physical (p = 0.035) and cognitive (p = 0.015) fatigue were elevated during treatment weeks 4 and 5. Affective fatigue did not change significantly. Anxiety, as rated with the Hospital Anxiety and Depression Scale, declined during RT (p = 0.002), but the Hospital Anxiety and Depression Scale depression score did not change significantly. IL-1beta, IL-6, and tumor necrosis factor-alpha levels did not change during therapy and did not correlate with fatigue. Peripheral blood cell levels declined significantly during therapy and were still low 2 months after treatment. Until treatment week 5, lymphocytes were reduced to almost 50% of their initial values. Hemoglobin levels did not correlate with fatigue. CONCLUSIONS: We observed an increase in fatigue during adjuvant RT of patients with breast cancer. Fatigue returned to pretreatment levels 2 months after treatment. No evidence was found that anxiety, depression, serum levels of IL-1beta, IL-6, tumor necrosis factor-alpha, or declining hemoglobin levels were responsible for the treatment-induced fatigue.

Daily CT planning during boost irradiation of prostate cancer. Feasibility and time requirements.

BACKGROUND: In the irradiation of prostate cancer internal organ movement leads to uncertainties in the daily localization of the clinical target volume. Therefore more or less large safety margins are added when designing the treatment portals. With daily CT planning internal organ movement can be compensated to some extent, safety margins can be reduced and irradiated normal tissue can be spared. The feasibility of daily CT-based 3D treatment planning is studied in a patient with localized prostate carcinoma using a new patient positioning system. METHODS: Daily CT planning was applied during boost irradiation of a patient with prostate cancer: After patient immobilization the pelvis was scanned in 3 mm CT slices. Planning was done with the BrainSCAN planning system for stereotactic body irradiation. The prostate was contoured in all slices and the safety margins of the micromultileafs were automatically set to the distance chosen by the physician (0.8 cm). Patient positioning was done with the BrainLAB ExacTrac positioning system on the basis of skin attached stereotactic body markers. Before each treatment verification images of the isocenter were taken. RESULTS: The total time requirement for planning and irradiation was about 1 hour 15 minutes. Patient positioning on the treatment couch took about 10 minutes. The accuracy of the positioning system was good (75% of the deviations were smaller than 3 mm). The shift of the single markers from CT scan to CT scan was more extensive than those of the center of all 7 markers combined (47% of the deviations were smaller than 3 mm). The location of the markers seems to influence the magnitude of their dislocation. CONCLUSION: Daily CT planning is feasible but time consuming. The new patient positioning system ExacTrac is an interesting tool especially for daily CT planning since conventional simulation can be omitted.

[Prostatic carcinoma: problems in the interpretation of rectal dose-volume histograms]. / Prostatakarzinom: Zur Problematik bei der Interpretation rektaler Dosis-Volumen-Histogramme.

BACKGROUND: Dose-volume histograms (DVHs) are used for the prediction and calculation of late radiation side effects. In literature the predictive value of rectal DVHs is controversially discussed. Differences in contouring might contribute to the contradicting results. In particular the cranial and caudal border of the contoured organ are not uniformly defined. PATIENTS AND METHODS: The DVHs of 12 patients who were treated with conformal radiotherapy for prostate cancer were investigated. Six of the patients suffered from mild rectal bleeding as a late side effect of radiotherapy. Six patients without rectal bleeding (minimal follow-up 30 months) matched for age, concomitant disease and treatment concept served as controls. Four different DVHs with 4 different definitions of the cranial and caudal rectal border were generated for each patient. For each of the 48 DVHs the percent volume fractions (V50, V80, V95) and absolute volume fractions (aV50, aV80, aV95) were calculated that received more than 50%, 80% and 95% of the reference dose. RESULTS: For every patient there were considerable variations in the volume fractions depending on the definition of the rectum borders (Table 1). The mean and median values of the percent and absolute volume fractions of the bleeding patients were higher than those of the non-bleeders no matter how the rectum borders were defined. None of the volume fractions could totally separate bleeding from non-bleeding patients. CONCLUSION: There is a high variability of absolute and percent volume fractions of rectal DVHs depending on how the rectal borders were defined. For the comparison and for the interpretation of rectal DVHs a uniform definition would be helpful.

Palliative radiotherapy of malignant melanoma with reactor fission neutron therapy (RENT): a prospective study.

To study the efficacy and safety of relatively low-dosed reactor fission neutron therapy (RENT) at the research reactor of the Technical University Munich, we treated 33 superficial lesions of 20 patients with advanced malignant melanoma by neutron beam alone (n = 22), mixed neutron/electron beam (n = 5), or by neutron beam after incomplete surgery (n = 6). Median tumor volume was 17.0 cm3. Median dose for neutron beam alone was 8.0 Gy and for mixed beam 3.0 Gy n + 45.3 Gy e-. Local tumor response, local control time, survival and treatment related toxicity were followed prospectively over a time period of 52 months. Overall response rate (CR;PR) after neutron beam alone and mixed beam therapy was 64% (CR: 36%) and 100% (CR: 60%), respectively. Observed differences between complete (CR) and incomplete (PR, NC) responding lesions were as follows: median tumor volume: 2.0 vs. 51.5 cm3, local control time: 13.3 vs. 3.7 months, median survival: 19.8 vs. 9.0 months. No severe acute or late sequelae could be observed. In conclusion, low-dosed RENT is an effective and well tolerated palliative treatment of superficial malignant melanoma utilizing the biologic advantage of diminished cellular repair capacity. Because melanoma lesions of small size (< or = 6 cm3) tend to respond completely, neutron beam should be performed at an early stage.

[Radiotherapy of the elderly patient. Radiotherapy tolerance and results in older patients]. / Strahlentherapie des alten Patienten. Verträglichkeit und Ergebnisse der Strahlentherapie älterer Personen.

BACKGROUND: Despite a growing number of elderly patients receiving radiation therapy little is known about side effects and outcome of irradiation in this section of the population. METHODS: In a review article epidemiologic data, aspects of radiation-biology as well as side effects and outcome of radiation therapy of elderly patients are discussed. RESULTS: Cancer incidence rises with age (Figure 1) and is exceeding 3.5% for males older than 85 years. With a life expectancy of more than 4 years, curative therapy is indicated even at this age. Furthermore several retrospective studies indicate that local control and disease-Specific survival after radiation therapy of elderly patients is comparable with that of younger persons (Tables 3 and 4). The exception contains elderly patients with Grade-III to IV gliomas or with rectal carcinoma who show a reduced survival which is perhaps caused by less aggressive combined treatment (tumor resection). Although some biological and molecular data indicate a rise in radiation sensitivity with growing age like the reduction of the capacity of some DNA-repair enzymes, there is no convincing evidence in animal studies or in retrospective clinical studies that radiation therapy is generally less well tolerated by older individuals (Tables 1 and 2). Some age-depending differences in organ toxicities are described in 3 large studies, which evaluate the data of patients who were enrolled in different EORTC-trials: Older patients suffer more of functional mucositis in case of radiation therapy to the head and neck, they have an increased weight loss and a higher frequency of late esophageal damage when irradiated in the thorax, and they show a higher prevalence of sexual dysfunction when treated with radiation therapy to the pelvis. On the other hand younger patients suffer more from acute toxicity like skin damage, nausea, and deterioration of the performance status during pelvic radiotherapy. When discussing the dose intensity of radiation therapy concomitant disease which leads to extensive atherosclerotic vessel damage should be kept in mind. Old patients should be monitored closely during therapy, since the loss of electrolytes or fluid is often not very well tolerated. CONCLUSION: The indication to radiation therapy of elderly cancer patients should take into account their performance status as well as the extent and the severity of comorbidity. Age per se is seldom a contraindication for radiation therapy. Regarding the available data in literature there is no indication for a dose reduction in radiation therapy only because of age, especially in the curative setting.

Therapy and prophylaxis of acute and late radiation-induced sequelae of the esophagus.

BACKGROUND: Radiation-induced esophagitis is a frequent acute side effect in curative and palliative radiotherapy of thoracal and cervical tumors. Late reactions are rare but might be severe. METHODS: A research for reports on prophylactic and supportive therapies of radiation-induced esophagitis was performed (Medline, Cancerlit, and others). RESULTS: Nutrition must be ensured and symptomatic relief of sequelae is important, especially in the case of dysphagia. The latter can be improved by topic or systemic analgetics. If esophageal spasm occurs, calcium antagonists might help. In case of gastro-esophageal reflux proton pump inhibitors should be used. There is no effective prophylactic measure for radiation esophagitis. Late side effects with clinical relevance are rare in conventional radiotherapy. Chronic ulcera, fistula or stenosis may develop. Before any treatment, a tumor infiltration of the esophagus should be excluded by biopsy. This can lead more often to late complications than radiation therapy itself. Nutrition should be ensured by endoscopic dilation, stent-implantation, or endoscopic percutaneous gastrostomy. Local injection of steroids might be used to avoid an early restenosis. CONCLUSIONS: An intensive symptomatic therapy of acute esophagitis is reasonable. Effective prophylaxis do not exist. Late radiation induced sequelae is rare. Therefore, a tumor recurrence should be excluded in cases of dysphagia. Securing nutrition by PEG, stent, or port is well in the fore.

Radiation proctitis. Clinical and pathological manifestations, therapy and prophylaxis of acute and late injurious effects of radiation on the rectal mucosa.

BACKGROUND: Often the rectum is the dose-limiting organ in curative radiation therapy of pelvic malignancies. It reacts with serous, mucoid, or more rarely bloody diarrhea. METHODS: A research for reports on prophylactic and supportive therapies of radiation-induced proctitis was performed (Medline, Cancerlit, and others). RESULTS: No proven effective prophylactic local or systemic therapies of radiation proctitis exist. Also, no reasonable causal medication is known. In the treatment of late radiation sequelae no clinically tested certain effective therapy exists, too. Antiinflammatory, steroidal or non-steroidal therapeutics as well as sucralfate can be used as topical measures. They will be successful in some patients. Side effects are rare and the therapy is cost-effective. Treatment failures can be treated by hyperbaric oxygen. This will achieve good clinical results in about 50% of the cases. Single or few mucosal telangiectasias with rectal bleeding can be treated sufficiently by endoscopic catheterization. CONCLUSION: Besides clinical studies acute proctitis should be treated just symptomatically. Radical surgery should be performed only when all conventional treatments have been uneffective, although no certain effective therapies of radiation-induced late proctitis exist.

[3-Dimensional irradiation planning in brain tumors. The advantages of the method and the clinical results]. / Dreidimensionale Bestrahlungsplanung bei Hirntumoren. Vorteile der Methode und klinische Ergebnisse.

PURPOSE: Radiotherapy became an important component in the treatment of brain gliomas. The aim of this study is to analyse several advantages of the three-dimensional conformal radiation therapy in comparison with a two-dimensional conventional technique and to present the clinical results of 43 patients with brain gliomas treated according to a three-dimensional planning. PATIENTS AND METHOD: Between January 1994 and December 1995, 43 patients with malignant brain gliomas (WHO III and IV) were treated in our department according to a three-dimensional treatment planning. The patients received a total irradiation dose of 60 Gy, 2 Gy/day, 5 days/week. The rate of survival was analysed in relation with the known prognostical factors: histology, Karnofsky index, age, resection status. In 10 patients a three-dimensional treatment planning was compared with a conventional two-dimensional planning: the volume of the normal brain tissue irradiated to high dose levels (95% isodose) and the normal tissue complication probability (NTCP) for the brain by Kutcher and Lyman were comparatively analysed. RESULTS: The survival rate for the whole group was 14 months. The histology of the tumor, age, Karnofsky index and resection status were important prognostical factors. The three-dimensional planning allows a 15 to 20% reduction in the volume of normal brain tissue irradiated to high dose levels (95% isodose). The NTCP is significantly lower using the three-dimensional technique (range 0.03% to 13%), in comparison with the two-dimensional conventional technique (range 0.1% to 26%). The value of NTCP increases with tumor volume. CONCLUSIONS: Concerning the tumor control and survival rate, the three-dimensional treatment planning shows no advantages compared to the standard conventional methods. The main advantage of the three-dimensional treatment planning is the possibility to spare normal brain tissue. The possibility to integrate mathematical models in the evaluation of the therapy could give this technique new dimensions.

[Abdominal irradiation in seminomas: improvement in its planning with MRT]. / Bestrahlung des Abdomens bei Seminomen: Verbesserung der Planung durch MRT.

BACKGROUND: Standard therapy for early stages of seminomas is the irradiation of the para-aortal and paracaval lymphatic vessels. PATIENTS AND METHOD: Prior to radiotherapy coronal T1-weighted MRI of the abdomen was performed including imaging of target volume and critical organs. The position and course of the large abdominal vessels are projected on simulator radiographs of the abdomen. The target volume is enclosed by blocks, which are individual formed with a 2 cm margin along the vessels. RESULTS: An irregular course of the vessels in 34% of the patients resulted in modifications of the radiation field compared with standard fields. Thus more than 10% of the volume of the left kidney could be taken out of field in 25% of the patients. Simultaneously fields were enlarged on contralateral side to make sure that the paracaval lymphatic drainage was enclosed. CONCLUSIONS: MRI-assisted planning of radiotherapy allows a more individualized treatment by visualization of the big abdominal vessels guiding the para-aortal lymphatics. The target volume is surely enclosed, healthy organs are optimal spared.