PURPOSE: The validity of tomotherapy-based simultaneous integrated boost (TOMOSIB) was assessed in terms of acute intestinal/urinary toxicity by comparing with 3-dimensional conformal radiotherapy (3DCRT) in cases of whole-pelvis radiation therapy (WPRT) for prostate cancer. MATERIALS AND METHODS: Thirty-eight consecutive patients who underwent curative WPRT were retrospectively reviewed. Twenty six (68.4%) received 3DCRT and the others (31.6%) were treated with TOMOSIB. A local boost to the prostate circumferential area was added to WPRT sequentially for 3DCRT and concomitantly for TOMOSIB. The total median prostate or prostatic bed dose was 64.8 Gy including median 45.0 Gy of WPRT. Acute toxicities were assessed according to RTOG criteria. RESULTS: Overall intestinal toxicity was lower in TOMOSIB group than 3DCRT group (p=0.008). When it was divided into rectum and non-rectum intestine (NRI), TOMOSIB showed borderline superiority only in NRI toxicity (p=0.047). For the urinary toxicity, there was no significant difference between two groups (p=0.796). On dosimetric analysis for the rectum and bladder, dose delivered to 80% (p<0.001) and volume receiving 25-40 Gy (p<0.001) were remarkably higher in 3DCRT. For the NRI, only maximum dose showed significant results between two groups (p<0.001). CONCLUSION: Intestinal toxicity should be verified with more detailed anatomic categorization such as rectum and NRI. TOMOSIB could not reduce urinary toxicity because of inevitably high dose exposure to the prostatic urethra. Current dosimetry system did not properly reflect intestinal/urinary toxicity, and suitable dosimetric guidelines are needed in TOMOSIB.
Adenocarcinoma/pathology/*radiotherapy ; Aged ; Humans ; Intestine, Small/*radiation effects ; Male ; Middle Aged ; Pelvis/*radiation effects ; Prostatic Neoplasms/pathology/*radiotherapy ; Radiation Injuries ; Radiotherapy Dosage ; Radiotherapy, Intensity-Modulated/*adverse effects/methods ; Rectum/radiation effects ; Retrospective Studies ; Urinary Bladder/*radiation effects

PURPOSE: The validity of tomotherapy-based simultaneous integrated boost (TOMOSIB) was assessed in terms of acute intestinal/urinary toxicity by comparing with 3-dimensional conformal radiotherapy (3DCRT) in cases of whole-pelvis radiation therapy (WPRT) for prostate cancer. MATERIALS AND METHODS: Thirty-eight consecutive patients who underwent curative WPRT were retrospectively reviewed. Twenty six (68.4%) received 3DCRT and the others (31.6%) were treated with TOMOSIB. A local boost to the prostate circumferential area was added to WPRT sequentially for 3DCRT and concomitantly for TOMOSIB. The total median prostate or prostatic bed dose was 64.8 Gy including median 45.0 Gy of WPRT. Acute toxicities were assessed according to RTOG criteria. RESULTS: Overall intestinal toxicity was lower in TOMOSIB group than 3DCRT group (p=0.008). When it was divided into rectum and non-rectum intestine (NRI), TOMOSIB showed borderline superiority only in NRI toxicity (p=0.047). For the urinary toxicity, there was no significant difference between two groups (p=0.796). On dosimetric analysis for the rectum and bladder, dose delivered to 80% (p<0.001) and volume receiving 25-40 Gy (p<0.001) were remarkably higher in 3DCRT. For the NRI, only maximum dose showed significant results between two groups (p<0.001). CONCLUSION: Intestinal toxicity should be verified with more detailed anatomic categorization such as rectum and NRI. TOMOSIB could not reduce urinary toxicity because of inevitably high dose exposure to the prostatic urethra. Current dosimetry system did not properly reflect intestinal/urinary toxicity, and suitable dosimetric guidelines are needed in TOMOSIB.
Adenocarcinoma/pathology/*radiotherapy ; Aged ; Humans ; Intestine, Small/*radiation effects ; Male ; Middle Aged ; Pelvis/*radiation effects ; Prostatic Neoplasms/pathology/*radiotherapy ; Radiation Injuries ; Radiotherapy Dosage ; Radiotherapy, Intensity-Modulated/*adverse effects/methods ; Rectum/radiation effects ; Retrospective Studies ; Urinary Bladder/*radiation effects

The influence of the position and radiation technique on the organs at risk (OARs) in radiotherapy of rectal cancer was evaluated. The relationship between the volume of irradiated small bowel (VSB) and acute bowel toxicity was determined. A total of 97 cases of rectal cancer were retrospectively randomized to receive radiotherapy with the designated treatment positions and radiation plans. Among 64 patients in the supine position, 32 patients were given three-dimensional conformal radiotherapy (3DCR) and 32 patients were subjected to intensity-modulated radiation therapy (IMRT) respectively. The rest 33 patients were treated with 3DCRT in the prone position with a belly board. The VSB was calculated for doses from 5 to 45 Gy at an interval of 5 Gy. With prescription dose in planned target volume (PTV) of 50 Gy, the dose distribution, conformal index for PTV (CI), dose-volume histogram (DVH) of OARs, the correlation of VSB and the acute toxicity were compared. The results were shown as follows: (1) Among the 3 methods, there were no differences in PTV's converge including V95 and D95; (2) For IMRT under a supine position, CIwas closest to 1, the mean dose of small bowel decreased (P<0.05), and the mean VSB from V30 to V45 significantly decreased (P<0.05). (3) For 3DCRT with a belly board under a prone position, the mean dose and the mean VSB from 40 to 45 Gy were less than those for 3DCRT under a supine position (P<0.05); (4) Mean proportion of VSB was significantly greater in the patients experiencing diarrhea grade 2-4 than in those with diarrhea grade 0-1 at dose levels from V30 to V45 (P<0.05). It was concluded that for the radiotherapy of rectal cancer, IMRT technique might decrease the high-dose VSB to reduce the risk of acute injury. 3DCRT with a belly board under a prone position is superior to 3DCRT under a supine position, which could be a second choice for radiation of rectal cancer.
Female ; Humans ; Intestine, Small ; pathology ; radiation effects ; Male ; Organs at Risk ; pathology ; radiation effects ; Prone Position ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted ; Radiotherapy, Conformal ; adverse effects ; Radiotherapy, Intensity-Modulated ; adverse effects ; Rectal Neoplasms ; pathology ; radiotherapy ; Urinary Bladder ; pathology ; radiation effects

Hyperthermia can enhance the radiation effect as a synergistic reaction in combined X-ray irradiation and hyperthermia; hyperthermia sensitize radilresistant S-phase cells and inhibit cellular recovery from sublethal damage. We fabricated 100 watts, 2450MHz microwave applicator for hyperthermia and planned the method and condition of heating and measured the temperature by usting Agar phantom as a preliminary test. For biological examination, 102 rats were divided into 4 groups as hyperthermia, X-ray irradiation(6Gy-15Gy), combined X-ray and hyperthermia, and normal control groups. Microscopic examination of the rectum and bladder was done and the results were as followings: 1. The microwave generator with 100 watts, 2450MHz magnetron could be heating up to 40degree-50degree C for one hour in living tissue. 2. The thermal distribution in tissue equivalent phantom with microwave can be maintained at 40degree-44degree C in area of 3cm in depth and 2-10cm in diameter. 3. In Hyperthermia alone group, there was submucosal edema of the rectum but no histologic change in the urinary bladder was seen. 4. The minimal necrosis of the mucosa was appeared in the rectum and bladder after 15days of 6Gy and 8Gy irradiation respectively. The minimal necrosis of the muscle layer of rectum and bladder was appeared after 15days of 8Gy and 60days of 10Gy irradiation respectively. 5. In combined group of radiation and hyperthermia, thermal enhancement ratio (calculated at mecrosis of mucosa and muscle layer) of rectum and bladder was 1.0, and it suggest that there is no change of tolerance dose of normal rectum and bladder.
Agar ; Animals ; Edema ; Fever* ; Heating ; Hot Temperature ; Microwaves* ; Mucous Membrane ; Necrosis ; Radiation Effects ; Rats* ; Rectum* ; Urinary Bladder*

The object of this study was to determine the radiation effect on the urinary bladder and to establish the basic date for optimal fraction schedule on the whole abdominal irradiation of the mice. Although radiation damage of the urinary bladder is one of the dose-limiting factor for treatment of lower abdominal cancer, such as uterine cervical or rectal cancer, systematic histopathological study of total dose and recovery duration is very rare, especially in conventional fractionation regimen of clinical use. Authors used 198 mice and analyzed histopathological findings according to total dose (40&50 GY) and recovery duration (1-15 weeks after completion of irradiation) The results were summarized as follows: 1. No definite difference of radiosensitivity was noted between male and female group. 2. Most of mucosal injuries were recovered within 14 weeks in 40 GY irradiated group. 3. Vascular injury and change of connective tissue were prominent and persisted even mild degree until 15 weeks after completion of irradiation in 50 GY irradiated group. 4. Although follow up duration of this study (105 days) was not enough to compare life span of mice, this study emphasized that precious schedule for treatment planning was necessary for preventing or reducing of late complication.
Animals ; Appointments and Schedules ; Connective Tissue ; Female ; Follow-Up Studies ; Humans ; Male ; Mice* ; Radiation Effects ; Radiation Tolerance ; Rectal Neoplasms ; Urinary Bladder* ; Vascular System Injuries

OBJECTIVETo evaluate the potential benefit of carbon ion radiotherapy (C-ion RT) through comparison with photon intensity-modulated radiotherapy (IMRT) in dose distribution for prostatic adenocarcinoma.

METHODSIn randomly selected 5 patients, treatment planning of C-ion RT (4 coplanar beams) and IMRT (7 coplanar fields) were worked out by computer working station. In order to make a meaningful comparison, it was defined that the 95% isodose surface had to cover 100% of the PTV in each plan; all dose was given as normalized dose with the definition of the minimum dose of the PTV being equal to 95% of prescribed dose. Dose-volume histograms (DVHs) of the tumor and organ-at-risks (OARs) were calculated. Volume irradiated more than or equal to some specified doses, conformity index ( CI) , and inhomogeneity coefficient (IC) of each treatment plan was compared, respectively.

RESULTSWith C-ion RT, the mean irradiated volumes (in %) of the rectum were significantly smaller than that with IMRT except for 95% dose level, and C-ion RT could provide complete protection to the posterior rectal wall. In addition, C-ion RT could also remarkably reduce the dose to the bladder, femoral heads and non-target normal tissues at each dose level. Dose conformation and homogeneity in the target volume of C-ion RT were better than that in IMRT (mean CI50%, 3.36 vs. 5.04, mean CI95%, 1.20 vs. 1.46, mean IC, 0.03 vs. 0.12).

CONCLUSIONCompared with IMRT, C-ion RT can obtain better dose distribution, and may reduce tumor recurrence and radiation-induced complications in prostatic adenocarcinoma.

Adenocarcinoma ; pathology ; radiotherapy ; Aged ; Carbon Radioisotopes ; therapeutic use ; Femur Head ; radiation effects ; Humans ; Male ; Prostatic Neoplasms ; pathology ; radiotherapy ; Radiotherapy Dosage ; Radiotherapy, Intensity-Modulated ; methods ; Rectum ; radiation effects ; Urinary Bladder ; radiation effects

The volumetric modulated arc therapy (VMAT) technique, in the form of RapidArc, is widely used to treat prostate cancer. The full-single arc (f-SA) technique in RapidArc planning for prostate cancer treatment provides efficient treatment, but it also delivers a higher radiation dose to the rectum. This study aimed to compare the dosimetric results from the new partial-single arc (p-SA) technique with those from the f-SA technique in RapidArc planning for prostate cancer treatment. In this study, 10 patients with low-risk prostate cancer were selected. For each patient, two sets of RapidArc plans (f-SA and p-SA) were created in the Eclipse treatment planning system. The f-SA plan was created using one full arc, and the p-SA plan was created using planning parameters identical to those of the f-SA plan but with anterior and posterior avoidance sectors. Various dosimetric parameters of the f-SA and p-SA plans were evaluated and compared for the same target coverage and identical plan optimization parameters. The f-SA and p-SA plans showed an average difference of ±1% for the doses to the planning target volume (PTV), and there were no clear differences in dose homogeneity or plan conformity. In comparison to the f-SA technique, the p-SA technique reduced the doses to the rectum by approximately 6.1% to 21.2%, to the bladder by approximately 10.3% to 29.5%, and to the penile bulb by approximately 2.2%. In contrast, the dose to the femoral heads, the integral dose, and the number of monitor units were higher in the p-SA plans by approximately 34.4%, 7.7%, and 9.2%, respectively. In conclusion, it is feasible to use the p-SA technique for RapidArc planning for prostate cancer treatment. For the same PTV coverage and identical plan optimization parameters, the p-SA technique is better in sparing the rectum and bladder without compromising plan conformity or target homogeneity when compared to the f-SA technique.
Aged ; Aged, 80 and over ; Femur Head ; radiation effects ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Organs at Risk ; radiation effects ; Penis ; radiation effects ; Prostatic Neoplasms ; pathology ; radiotherapy ; Radiometry ; methods ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted ; Radiotherapy, Intensity-Modulated ; methods ; Rectum ; radiation effects ; Urinary Bladder ; radiation effects

BACKGROUNDCaffeine suppresses ataxia telangiectasia and Rad3 related and ataxia telangiectasia mutated (ATM) activities; ATM is the major kinase for DNA damage detection. This study aimed to investigate the effects of caffeine on DNA damage responses in cells from the bladder cancer cell line RT4 those were exposed to ionizing radiation (IR).

METHODSImmunofluorescent staining was performed to investigate changes in the proteins involved in DNA damage responses with or without caffeine. A mouse xenograft model was used to study the effects of caffeine on the DNA damage responses. Western blotting was used to investigate the effects of caffeine pretreatment on the ATM-Chk2-p53-Puma axis, while real-time polymerase chain reaction (RT-PCR) assessed changes in messenger RNA levels of p53 and downstream targets responding to IR. Finally, terminal deoxynucleotidyl transferase-dUTP nick end labeling assay. Western blotting and colony formation assay were used to measure the effects of caffeine on radiation-related apoptosis. All of the data were analyzed with a two-tailed Student's t-test.

RESULTSImmunofluorescent staining showed that caffeine pretreatment profoundly suppressed the formation of γH2AXand p53-binding protein 1 foci in RT4 cells in response to irradiation. Cellular and animal experiments suggested that this suppression was mediated by suppression of the ATM-Chk2-p53-Puma DNA damage-signaling axis. RT-PCR indicated caffeine also attenuated transactivation of p53 and p53-inducible genes. The colony formation assay revealed that caffeine displayed radioprotective effects on RT4 cells in response to low-dose radiation compared to the radiosensitization effects on T24 cells.

CONCLUSIONCaffeine may inhibit IR-related apoptosis of bladder cancer RT4 cells by suppressing activation of the ATM-Chk2-p53-Puma axis.

Animals ; Apoptosis ; drug effects ; radiation effects ; Caffeine ; pharmacology ; Cell Cycle Proteins ; metabolism ; Cell Line, Tumor ; Checkpoint Kinase 2 ; metabolism ; Humans ; Immunohistochemistry ; Male ; Mice ; Mice, Nude ; Radiation, Ionizing ; Real-Time Polymerase Chain Reaction ; Signal Transduction ; drug effects ; Tumor Suppressor Protein p53 ; metabolism ; Urinary Bladder Neoplasms ; radiotherapy