Phase I/II trial of definitive carbon ion radiotherapy for prostate cancer: evaluation of shortening of treatment period to 3 weeks.

BACKGROUND: The purpose of this study was to evaluate the feasibility of a new shortened 3-week treatment schedule of carbon ion radiotherapy (CIRT) for prostate cancer. METHODS: Beginning in May 2010, patients with T1b-T3bN0M0, histologically proven prostate adenocarcinoma were enrolled in the phase II trial of CIRT. Patients received 51.6 GyE in 12 fractions over 3 weeks (protocol 1002). The primary end point was defined as the incidence of late adverse events that were evaluated based on the Common Terminology Criteria for Adverse Events version 4.0. Biochemical failure was determined using the Phoenix definition (nadir +2.0 ng ml(-1)). RESULTS: Forty-six patients were enrolled, and all patients were included in the analysis. The number of low-, intermediate-, and high-risk patients was 12 (26%), 9 (20%), and 25 (54%), respectively. The median follow-up period of surviving patients was 32.3 months. Two patients had intercurrent death without recurrence, and the remaining 44 patients were alive at the time of this analysis. In the analysis of late toxicities, grade 1 (G1) rectal haemorrhage was observed in 3 (7%) patients. The incidence of G1 haematuria was observed in 6 (13%) patients, and G1 urinary frequency was observed in 17 (37%) patients. No ⩾G2 late toxicities were observed. In the analysis of acute toxicities, 2 (4%) patients showed G2 urinary frequency, and no other G2 acute toxicities were observed. CONCLUSIONS: The new shortened CIRT schedule over 3 weeks was considered as feasible. The analysis of long-term outcome is warranted.

Quantitative autistic traits ascertained in a national survey of 22 529 Japanese schoolchildren.

OBJECTIVE: Recent epidemiologic studies worldwide have documented a rise in prevalence rates for autism spectrum disorders (ASD). Broadening of diagnostic criteria for ASD may be a major contributor to the rise in prevalence, particularly if superimposed on an underlying continuous distribution of autistic traits. This study sought to determine the nature of the population distribution of autistic traits using a quantitative trait measure in a large national population sample of children. METHOD: The Japanese version of the Social Responsiveness Scale (SRS) was completed by parents on a nationally representative sample of 22 529 children, age 6-15. RESULTS: Social Responsiveness Scale scores exhibited a skewed normal distribution in the Japanese population with a single-factor structure and no significant relation to IQ within the normal intellectual range. There was no evidence of a natural 'cutoff' that would differentiate populations of categorically affected children from unaffected children. CONCLUSION: This study provides evidence of the continuous nature of autistic symptoms measured by the SRS, a validated quantitative trait measure. The findings reveal how paradigms for diagnosis that rest on arbitrarily imposed categorical cutoffs can result in substantial variation in prevalence estimation, especially when measurements used for case assignment are not standardized for a given population.

Effect of dietary Rhodobacter capsulatus on lipid fractions and egg-yolk fatty acid composition in laying hens.

The present study was conducted to investigate the effect of dietary Rhodobacter capsulatus on lipid fractions and egg-yolk fatty acid composition in laying hens. Thirty-six laying hens (30 weeks old) were randomly assigned into two dietary groups fed diets with (0.04%) or without (control) R. capsulatus for a 60-day feeding trial. Dietary R. capsulatus decreased (p < 0.05) serum and hepatic cholesterol and increased (p < 0.05) the excreta cholesterol, and resultant lower (p < 0.05) cholesterol contents in egg yolk. The concentration of polyunsaturated fatty acids (PUFA) and ratio to saturated fatty acids in egg yolk was improved (p < 0.05) by dietary R. capsulatus. The concentration of hepatic bile acid was increased (p < 0.05) and excreta bile acid was decreased (p < 0.01) in the laying hens fed R. capsulatus diet. The incorporation of 1-(14) C-palmitic acid into hepatic lipids and lipid fractions was increased (p < 0.05) in laying hens fed R. capsulatus diet. Moreover, dietary R. capsulatus did not appear to cause any adverse effects on laying hen performances. Therefore, dietary supplementation of R. capsulatus in layer diets may be a feasible means of producing eggs with lower cholesterol and higher PUFA contents for health conscious consumers.

Hypocholesterolemic effect of karaya saponin in Japanese laying quails (Coturnix coturnix japonica).

The effect of karaya saponin supplementation on the serum and egg yolk cholesterol and fatty acid composition in egg yolk were investigated in Japanese quails. A total of 80 Japanese quails aged 5 weeks were equally divided into four groups of 20. Four levels (0, 25, 50 and 75 mg/kg feed) of karaya saponin were included in the basal diet and experiment was lasted for 6 weeks. The cholesterol fractions in the egg yolk and serum were measured by enzymatic assay, and the fatty acid composition in egg yolk was determined by gas chromatography. The results revealed that the supplementation of 75 mg/kg karaya saponin significantly reduced (p < 0.05) cholesterol and triglycerides concentration in serum and egg yolk. High-density lipoprotein-cholesterol was increased, low-density lipoprotein-cholesterol and the atherogenic index were decreased (p < 0.05) by the dietary supplementations. Hepatic cholesterol was reduced (p < 0.05) by the 25 mg/kg karaya saponin. A higher degree of yolk colour was improved (p < 0.05) when 75 mg/kg saponin was supplemented in the diet. The concentration of polyunsaturated fatty acids (PUFA) in egg yolk was increased (p < 0.05) in a dose-dependent manner in quails fed the supplemented diet than the control diet. The ratio of PUFA to saturated fatty acids in egg yolk was improved (p < 0.05) by 75 mg/kg feed karaya saponin-supplemented diet. Therefore, the dietary supplementation of 75 mg/kg karaya saponin may be a feasible means of producing quail eggs with lower cholesterol and higher PUFA content for health conscious consumers.

Effect of dietary karaya saponin on serum and egg yolk cholesterol in laying hens.

1. The objective of the study was to investigate the effect of dietary karaya saponin on cholesterol deposition in laying hens. 2. A total of 40 Boris Brown hens were randomly assigned at 20 weeks of age to 4 treatment groups and fed on diets supplemented with 0 (control), 25, 50 or 75 mg/kg karaya saponin for an 8-week experimental period. 3. After 8 weeks of dietary supplementation, karaya-saponin-treated groups had significantly lower serum cholesterol (23·0%) and triglycerides but increased high density lipoproteins cholesterol concentration than controls, irrespective of karaya saponin content in the diet. Egg yolk cholesterol and triglycerides were also significantly reduced by dietary karaya saponin. Hepatic cholesterol and triglycerides were significantly reduced by karaya saponin but bile acids concentration in the faeces and liver were significantly increased by karaya saponin. The concentrations of oleic, linoleic and linolenic acids in the yolk were greater in hens receiving karaya saponin than in controls. Karaya saponin significantly increased egg production, feed efficiency and yolk colour compared with controls. Karaya saponin tended to increase egg weight, feed consumption, Haugh units, albumen weight and yolk index. 4. In conclusion, karaya saponin is a potential agent for reducing yolk cholesterol concentration together with an overall increase of production performance and improvement in egg quality.

Effects of karaya saponin and Rhodobacter capsulatus on yolk cholesterol in laying hens.

1. It has been reported that karaya saponin and Rhodobacter capsulatus individually have hypocholesterolaemic activity in laying hens. This study focuses on the effect of adding karaya saponin with R. capsulatus to hen's diet with regard to serum and egg yolk cholesterol and triglycerides. 2. A total of 56 Boris Brown laying hens were divided into 7 groups at 20 weeks of age. Combinations of 25, 50, 75 mg kg(-1) karaya saponin and R. capsulatus 200 and 400 mg kg(-1) were used as treatment groups. 3. After 8 weeks of supplementation, the effects of all the combinations of karaya saponin and R. capsulatus on serum and egg yolk cholesterol, triglycerides, and high-density lipoprotein (HDL)-cholesterol were greater than either karaya saponin or R. capsulatus alone. The combination of karaya saponin 50 mg kg(-1)+ R. capsulatus 400 mg kg(-1) exhibited the greatest reduction of serum (325%) and yolk (225%) cholesterol and the greatest increase of faecal, liver bile acids and yolk fatty acid (oleic, linoleic and linolenic) concentrations. In addition, egg production and yolk colour were significantly improved by the combined use of karaya saponin and R. capsulatus supplementation. 4. Therefore, the dietary supplementation of karaya saponin and R. capsulatus may lead to the production of a low-cholesterol egg, with production performance maintained at a standard level.

Effect of glutathione on the development of rat embryos following microinsemination.

PURPOSE: The present study was carried out to evaluate the role of glutathione on rat embryo developmental potential after ICSI. We observed the effects of glutathione on the development of non-treated rat embryos, ICSI embryos and embryos with sham injection treatment. The development of glutathione-microinjected embryos was also observed. METHODS: Oocytes and fertilized embryos were obtained from superovulated Wistar-Imamichi rats and cultured in mR1ECM medium. Oocytes and embryos were then allowed to develop to assess the effect of glutathione on the development rate in intact embryos, micro-injected embryos and ICSI embryos. RESULTS: (1) In the intact embryo, the proportion of blastocyst stage development increased when 0.01 mM GSH was added to the medium compared to the control. (2) Microinjection of glutathione (GSSG, GSH) into the embryo increased development at each stage, and the addition of 0.2 nM GSSG or GSH significantly increased blastocyst development, in comparison to that of the control (P < 0.05). (3) Compared to the control, all the GSSG and GSH concentrations improved damaged blastocyst development, where 0.01 mM GSH improved significantly (P < 0.05). (4) The addition of glutathione in the medium increased the rate of blastocyst development after ICSI. A significantly higher number of TE and total cells were obtained in the micro-injected embryo with both of the 0.02 mM GSSG and GSH treatments (P < 0.05). CONCLUSIONS: The addition of glutathione into the culture media can improve early embryo development and is capable of repairing the damage of ICSI rat embryos.

The beneficial effect of fructose and glucose on in vitro maturation and the fertilization of porcine oocytes.

PURPOSE: This study was conducted to investigate the effects of supplementing fructose in the culture medium on in vitro maturation (IVM), in vitro fertilization (IVF), and metabolism of porcine oocytes. METHODS: Porcine oocytes were matured in vitro in modified North Carolina State University 37 medium (NCSU-37) and then supplemented with either glucose (5.5 mM), fructose (5.5 mM), or glucose (2.75 mM) plus fructose (2.75 mM). The maturation and fertilization of oocytes, and the incorporation and oxidation of 14C-glucose, 14C-fructose, and 14C-methionine in oocytes at different stages of development were examined. RESULTS: The supplementation of glucose plus fructose significantly promoted (P < 0.05) oocytes germinal vesicle break down (GVBD), maturation to metaphase II (MII), penetration by spermatozoa, and male pronuclear formation compared with glucose. The incorporation and oxidation of 14C-methionine into the oocyte significantly increased (P < 0.05) with glucose plus fructose supplementation than glucose. A significantly higher (P < 0.05) rate of incorporation and oxidation was achieved with 14C-fructose compared to 14C-glucose. CONCLUSIONS: Glucose plus fructose supplementation improved maturation, penetration by spermatozoa, male pronuclear formation, and energy metabolism by porcine oocytes.

Comparison between 3-D and z-axis automatic tube current modulation technique in multidetector-row CT.

In this study, the 3-D automatic tube current modulation (3-D ATCM) technique was compared with the z-axis ATCM technique on multidetector-row CT. Absorbed dose measurements were performed by inserting an ion chamber into the phantoms, and objective image noise shown as the standard deviation of CT value in Hounsfield units was measured on the obtained images. The ratio of absorbed doses with 3-D ATCM technique to z-axis ATCM technique was 94.7% using an elliptical cylinder phantom with an inner cylinder phantom and 96.3% using an elliptical cylinder phantom without an inner cylinder phantom. Differences in objective noise between the 3-D ATCM technique and z-axis ATCM technique were within a tolerable range compared with the setting noise index. Therefore, the 3-D ATCM technique effectively optimises the radiation dose, while maintaining an appropriate image quality compared with z-axis ATCM technique.

Effect of dietary Rhodobacter capsulatus on cholesterol concentration and fatty acid composition in broiler meat.

The study was designed to investigate the effects of dietary Rhodobacter capsulatus on cholesterol concentration and fatty acid composition in broiler meat. A total of 45 two-week-old male broiler chicks were randomly assigned into 3 treatment groups and fed ad libitum diets supplemented with 0 (control), 0.02, and 0.04% R. capsulatus for a 6-wk feeding period. The results of this study revealed that the supplementation of 0.04% R. capsulatus in diet reduced (P < 0.05) cholesterol and triglyceride concentrations in broiler meat. The concentrations (expressed as a percentage of total fatty acids) of oleic acid (18:1), linoleic acid (18:2), and linolenic (18:3) acid in thigh muscle and breast muscle were higher (P < 0.05) in the broilers fed the 0.04% R. capsulatus supplemented diet than in the broilers fed the control diet. The ratio of unsaturated fatty acids to saturated fatty acids was greater (P < 0.05) in both muscles of broilers fed the 0.04% R. capsulatus supplemented diet than the control diet. In addition, the concentrations of serum cholesterol and triglyceride, and hepatic cholesterol and triglyceride were also reduced (P < 0.05) by dietary R. capsulatus. Compared with the control diet, the 0.04% R. capsulatus supplemented diet reduced (P < 0.05) the ratio of low-density lipoprotein-cholesterol to high-density lipoprotein-cholesterol. Moreover, the supplementation of R. capsulatus in broiler diets did not show any adverse effect on production performance. Therefore, these results conclude that the application of R. capsulatus into diet may be feasible to reduce cholesterol concentration and improve the ratio of unsaturated fatty acids to saturated fatty acids in broiler meat.

Effect of dietary Rhodobacter capsulatus on egg-yolk cholesterol and laying hen performance.

The present study was conducted to investigate the effects of dietary Rhodobacter capsulatus on the laying hen. A total of forty 23-wk-old Hy-Line Brown laying hens were randomly assigned into 4 treatment groups (10 laying hens/group) and fed diets supplemented with 0 (control), 0.01, 0.02, and 0.04% R. capsulatus during the 60-d feeding period. Dietary supplementation of R. capsulatus (0.04%) reduced (P < 0.05) cholesterol and triglycerides concentration in serum (15 and 11%), as well as in egg-yolk (13 and 16%) over a 60-d feeding period. Cholesterol and triglycerides concentrations in serum as well as egg-yolk were changed linearly in accordance with increasing levels of dietary R. capsulatus. Supplementation of R. capsulatus in diets increased high-density lipoprotein cholesterol level and decreased (P < 0.05) atherogenic index in serum. Yolk color was improved (P < 0.05) in the group fed the 0.04% R. capsulatus supplemented diet compared with the control group. Hepatic cholesterol and triglycerides were reduced (P < 0.05) by 0.04% R. capsulatus. Moreover, the supplementation of R. capsulatus in layer diets did not appear to cause any adverse effects on egg production, shell weight, shell thickness, Haugh unit, yolk index, and feed conversion efficiency compared with the same parameters for the control laying hens. It is postulated that known and unknown factors are present in R. capsulatus presumably responsible for the hypocholesterolemic effect on laying hens. Therefore, the dietary supplementation of R. capsulatus may lead to the development of low-cholesterol chicken eggs as demanded by health-conscious consumers.

Overexpression of mitochondrial manganese superoxide dismutase protects against radiation-induced cell death in the human hepatocellular carcinoma cell line HLE.

We investigated the potential role of mitochondrial manganese superoxide dismutase (Mn-SOD) in protective activity against irradiation by analyzing cell viability by a colony formation assay and by detecting apoptosis in stably human Mn-SOD gene-transfected HLE, a hepatocellular carcinoma cell line. We found that overexpression of Mn-SOD reduced the levels of reactive oxygen species in the mitochondria and intracellular phospholipid peroxidation product (4-hydroxy-2-nonenal) and prevented cell death. The production of intracellular nitric oxide after irradiation was not changed by Mn-SOD overexpression. The results suggested that Mn-SOD might play an important role in protecting cells against radiation-induced cell death by controlling the generation of mitochondrial reactive oxygen species and intracellular lipid peroxidation.

Radiological protection in ion beam radiotherapy: practical guidance for clinical use of new technology.

Recently introduced technologies in radiotherapy have significantly improved the clinical outcome for patients. Ion beam radiotherapy, involving proton and carbon ion beams, provides excellent dose distributions in targeted tumours, with reduced doses to the surrounding normal tissues. However, careful treatment planning is required in order to maximise the treatment efficiency and minimise the dose to normal tissues. Radiation exposure from secondary neutrons and photons, particle fragments, and photons from activated materials should also be considered for radiological protection of the patient and medical staff. Appropriate maintenance is needed for the equipment and air in the treatment room, which may be activated by the particle beam and its secondary radiation. This new treatment requires complex procedures and careful adjustment of parameters for each patient. Therefore, education and training for the personnel involved in the procedure are essential for both effective treatment and patient protection. The International Commission on Radiological Protection (ICRP) has provided recommendations for radiological protection in ion beam radiotherapy in Publication 127 Medical staff should be aware of the possible risks resulting from inappropriate use and control of the equipment. They should also consider the necessary procedures for patient protection when new technologies are introduced into clinical practice.

Quantitative dose-response analysis of salivary function following radiotherapy using sequential RI-sialography.

A total of 216 99mTc-pertechnetate-sialographies, by applying stimulations by citric acid, were performed for studying radiation effects on the salivary glands in 145 patients. From a scintigram of the salivary gland, the time-activity-curves were obtained for analysis of salivary function. The shape of the time-activity-curve with respect to stimulus-response pattern was classified into four types according to the degree of radiation-induced dysfunction. We found that the acid stimulation was enhancing accumulation of the isotope into the salivary gland as well as influencing salivary discharge. A ratio (Rc) of pre- and post-stimulation counts permitted a construction of quantitative dose-response curves; the curve for the parotids had a slight rise of Rc's over 0-20 Gy, whereas that for the submandibular glands had a significant rise over 10-30 Gy; in both glands the rise of Rc's was followed by a steep fall. The parotids appeared to be more sensitive to radiation than the submandibular glands at 0-3 months following 20-70 Gy, but after 3 months both glands were similarly impaired. The gland volume irradiated was also of great importance in determining the degree of salivary dysfunction. The maximum uptakes averaged per unit area (salivary-to-background ratio) and determined during the initial 30 minutes were greater in the submandibular than in the parotid glands following greater than 20 Gy. In both glands the maximum uptakes were gradually impaired with time over 3-36 months following 50-70 Gy.

Indications of particle radiation therapy in the treatment of carcinoma of the esophagus.

Studies were made to evaluate the role of radiations in the treatment of carcinoma of the esophagus to confirm indications for charged particles. Results of the studies showed that prognosis of the patients treated with radiations depend strongly on length of tumor as well as on invasion of tumor cells into the adventitia of the esophagus. It was concluded that patients suffering from carcinoma of the esophagus less than 8 cm length are indicated for particle radiations.

High linear energy transfer carbon radiation effectively kills cultured glioma cells with either mutant or wild-type p53.

PURPOSE: A mutation in the p53 gene is believed to play an important role in the radioresistance of many cancer cell lines. We studied cytotoxic effects of high linear energy transfer (LET) carbon beams on glioma cell lines with either mutant or wild-type p53. METHODS AND MATERIALS: Cell lines U-87 and U-138 expressing wild-type p53 and U-251 and U-373 expressing mutant p53 were used. These cells were irradiated with 290 MeV/u carbon beams generated by the Heavy Ion Medical Accelerator in the National Institute of Radiologic Science or X-rays. A standard colony-forming assay and flow cytometric detection of apoptosis were performed. Cell cycle progression and the expression of p53, p21, and bax proteins were examined. RESULTS: High LET carbon radiation was more cytotoxic than low LET X-ray treatment against glioma cells. The effects of the carbon beams were not dependent on the p53 gene status but were reduced by G(1) arrest, which was independent of p21 expression. The expression of bax remained unchanged in all four cell lines. CONCLUSION: These results indicate that high LET charged particle radiation can induce cell death in glioma cells more effectively than X-rays and that cell death other than p53-dependent apoptosis may participate in the cytotoxicity of heavy charged particles. Thus, it might prove to be an effective alternative radiotherapy for patients with gliomas harboring mutated p53 gene.

Relationship between p21/WAF-1/CIP-1 and apoptosis in cervical cancer during radiation therapy.

PURPOSE: P21/WAF-1/CIP-1 was not considered to be involved in the regulation of apoptosis, an important indicator of radiosensitivity. However, it has been reported recently that apoptosis was suppressed when p21 expressed. The purpose of this study was to clarify the relationship between p21 and apoptosis and to evaluate the role of p21 in cervical cancer during radiation therapy (RT). METHODS AND MATERIALS: Twenty-one patients with cervical cancer were treated by RT. Tissue samples were obtained from cervical tumors of all patients before RT, and 6 hours after the fifth dose of 1.8 Gy (5th Dose). Samples were subjected to nick end labeling for apoptosis and immunohistochemical staining for p21 and p53 antigen expression. RESULTS: The mean apoptotic index, p21 labeling index and p53 labeling index were 0.27%, 9.24% and 6.60%, respectively, before RT and increased significantly to 1.20%, 17.5% and 13.9%, respectively, after 5th Dose. The apoptotic index at 5th Dose was inversely correlated with the p21 labeling index (r = -0.50, p = 0.025). Furthermore, a positive correlation was observed between the p21 and p53 labeling indices both before RT and at 5th Dose (r = 0.52, p = 0. 02; r = 0.63, p < 0.01, respectively). CONCLUSION: Our results demonstrate that apoptosis and expression of p21 and p53 were induced in cervical cancer during RT. p21 expression was dependent on p53 expression and moreover, it is suggested-that p21 might be a potential suppressor of radiation-induced apoptosis in cervical cancer during RT.

The value of treatment planning using CT and an immobilizing shell in radiotherapy for paranasal sinus carcinomas.

This article describes a method which uses CT scans and immobilizing shells radiation treatment planning (CT-assisted planning) for paranasal sinus carcinomas and the value of this method on the treatment outcome. Results of the treatment for 82 patients who had CT-assisted planning were compared with that of 88 patients who had no such treatment planning. It has been concluded that the combined use of CT and the shell in treatment planning permitted a 3-dimensional localization of both the tumor and critical normal structures with great accuracy, leading to an improved long-term survival and a reduced complication rate. The multivariate regression analysis for predicting significant prognostic factors also confirmed the valuable role of CT in terms of survival and primary tumor control. The actuarial 5-year survival rate was 51% in all patients, whereas, by using CT-assisted planning, it was improved to 61%. The improved survival was observed among the patients with tumors of the suprastructures where tumors were located adjacent to the critical organs (brain and eye). Major complications attributable to radiation have included instances of brain and ocular damage. CT-assisted planning, however, has been proven effective in avoiding brain necrosis and preserving eye sight.

Progesterone receptor is a favorable prognostic factor of radiation therapy for adenocarcinoma of the uterine cervix.

PURPOSE: The prognostic significance of the expression of estrogen receptors (ER) and progesterone receptors (PgR) in adenocarcinoma of the uterine cervix has been controversial. Hence, the relationship between the expression of the hormone receptors and clinical outcome was evaluated for patients with adenocarcinoma treated with radiation therapy alone. MATERIALS AND METHODS: This study involved 66 patients with cervical adenocarcinoma consisting of 44 adenocarcinomas and 22 adeno-squamous cell carcinomas. They received radiation therapy at the National Institute of Radiological Sciences Hospital between 1962 and 1993. The mean age of the patients was 62. 0 +/- 12.0 years (range, 36-82 years). The numbers of patients with Stage I, II, III, and IV diseases were 7, 17, 27, and 15, respectively. Their ER and PgR statuses were investigated immunohistochemically using biopsy specimens excised from the cervical tumors before radiation therapy. RESULTS: ER staining was positive in 12 patients (19%). ER status did not correlate with the 5-year cause-specific, local-control, and disease-free survivals. PgR staining was positive in 12 patients (19%). The disease-free survival rate of PgR-positive patients was significantly higher than that of PgR-negative patients (p = 0.044). Although PgR status did not reach statistical significance in relation to the 5-year cause-specific survival and local-control survival, the better survival was due to less local recurrence rather than to less distant metastasis. CONCLUSION: The present study suggested that PgR status was associated with prognosis after radiation therapy for adenocarcinoma of the uterine cervix.

X-rays vs. carbon-ion tumor therapy: cytogenetic damage in lymphocytes.

PURPOSE: To measure chromosomal aberrations in peripheral blood lymphocytes from cancer patients treated with X-rays or carbon ions (C-ions). METHODS AND MATERIALS: Blood samples from patients diagnosed for esophageal or uterine cervical cancer were obtained before, during, and at the end of the radiation treatment. The novel technique of interphase chromosome painting was used to detect aberrations in prematurely condensed chromosomes 2 and 4. The fraction of aberrant lymphocytes was measured as a function of the dose to the tumor volume. For comparison, blood samples were also exposed in vitro to X-rays or to carbon ions accelerated at the HIMAC. RESULTS: C-ions were more efficient than X-rays in the induction of chromosomal aberrations in vitro. In patients with similar pathologies, tumor positions, and radiation field sizes, however, C-ions induced a lower fraction of aberrant lymphocytes than X-rays during the treatment. The initial slope of the dose-response curve for the induction of chromosomal aberrations during the treatment was correlated to the relative decrease in the number of white blood cells and lymphocytes during the treatment. CONCLUSION: C-ions induce a lower level of cytogenetic damage in lymphocytes than X-rays, reducing the risk of bone marrow morbidity.