Fractionated radiotherapy (RT) is widely used in cancer therapy for its advantages in the preservation of normal tissues. However, repopulation of surviving tumor cells during fractionated RT limits the efficacy of RT. In fact, repopulating tumors often acquire radioresistance and this is the major cause of failure of RT. We have recently demonstrated that human tumor cells acquire radioresistance when exposed to fractionated radiation (FR) of X-rays every 12 hours for 1 month. The acquired radioresistance was associated with overexpression of cyclin D1, a result of a series of molecular changes; constitutive activation of DNA-PK and AKT with concomitant down-regulation of glycogen synthase kinase-3β (GSK3β) which results in suppression of cyclin D1 proteolysis. Aberrant cyclin D1 overexpression in S-phase induced DNA double strand breaks which activated DNA-PK and established the vicious cycle of cycling D1 overexpression. This overexpression of cyclin D1 is responsible for the radioresistance phenotype of long-term FR cells, since this phenotype was completely abrogated by treatment of FR cells by the API-2, an AKT inhibitor or by a Cdk4 inhibitor. Thus, targeting the AKT/GSK3β/cyclin D1/Cdk4 pathway can be an efficient modality to suppress acquired radioresistance of tumor cells. In this article, I overview the newly discovered molecular mechanisms underlying acquired radioresistance of tumor cells induced by FR, and propose a strategy for eradication of tumors using fractionated RT by overcoming tumor radioresistance.

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Local recurrence and distant metastasis frequently occur after radiation therapy for cancer and can be fatal. Evidence obtained from radiochemical and radiobiological studies has revealed these problems to be caused, at least in part, by a tumor-specific microenvironment, hypoxia. Moreover, a transcription factor, hypoxia-inducible factor 1 (HIF-1), was identified as pivotal to hypoxia-mediated radioresistance. To overcome the problems, radiation oncologists have recently obtained powerful tools, such as "simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT), which enables a booster dose of radiation to be delivered to small target fractions in a malignant tumor", "hypoxia-selective cytotoxins/drugs", and "HIF-1 inhibitors" etc. In order to fully exploit these innovative and interdisciplinary strategies in cancer therapy, it is critical to unveil the characteristics, intratumoral localization, and dynamics of hypoxia/HIF-1-active tumor cells during tumor growth and after radiation therapy. We have performed optical imaging experiments using tumor-bearing mice and revealed that the locations of HIF-1-active tumor cells changes dramatically as tumors grow. Moreover, HIF-1 activity changes markedly after radiation therapy. This review overviews 1) fundamental problems surrounding tumor hypoxia in current radiation therapy, 2) the function of HIF-1 in tumor radioresistance, 3) the dynamics of hypoxic tumor cells during tumor growth and after radiation therapy, and 4) how we should overcome the difficulties with radiation therapy using innovative interdisciplinary technologies.

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In this study we first evaluated the general radioprotective efficacy of Se, Zn and Mn (4 μg/ml each) plus Lachesis muta venom (4 ng/ml) combination (O-LM) by determining survival on rats irradiated with lethal doses of gamma-rays. The aim of the second part of the study was to investigate the O-LM ability to prevent ionizing radiation-induced damage on small intestine, bone marrow and submandibular glands. Hence, histological characteristics and functional studies, together with proliferation and apoptotic marker levels on whole body irradiated rats with a 5 Gy dose were evaluated. Results show that all animals of the untreated group died after whole body irradiation with 8 and 10 Gy while 60 day-survival was more than 80% and 40% in O-LM-treated animals, respectively. Histopathological examinations revealed a high degree of small intestine and submandibular gland radioprotection 3 days post-irradiation. O-LM inhibited histological damage on small intestine, restoring the radiation-induced reduction in villous height and crypt number. O-LM prevented radiation-induced loss of salivary gland function and morphological alterations. These effects were associated to a complete inhibition of radiation-induced apoptosis. Furthermore, studies performed 30 days post-irradiation revealed that O-LM significantly improved bone marrow repopulation, increasing all medullar progenies to the extent of the non-irradiated animals, and completely prevented permanent submandibular gland alterations. Based on the present results and taking into account that O-LM is being safely administered in phase I clinical trial as an immunomodulator, we conclude that O-LM is a non-toxic promising approach to achieve radioprotection for patients undergoing radiotherapy.

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The effect of hyperoxygenation with carbogen (95% O₂ + 5% CO₂) inhalation on RIF-1 tumor pO₂ and its consequence on growth inhibition with fractionated radiotherapy is reported. The temporal changes in the tumor pO₂ were assessed by in vivo Electron Paramagnetic Resonance (EPR) oximetry in mice breathing 30% O₂ or carbogen and the tumors were irradiated with 4 Gy/day for 5 consecutive days; a protocol that emulates the clinical application of carbogen. The RIF-1 tumors were hypoxic with a tissue pO₂ of 5–9 mmHg. Carbogen (CB) breathing significantly increased tumor pO₂, with a maximum increase at 22.9–31.2 min on days 1–5, however, the magnitude of increase in pO₂ declined on day 5. Radiotherapy during carbogen inhalation (CB/RT) resulted in a significant tumor growth inhibition from day 3 to day 6 as compared to 30%O₂/RT and carbogen (CB/Sham RT) groups. The results provide unambiguous quantitative information on the effect of carbogen inhalation on tumor pO₂ over the course of 5 days. Tumor growth inhibition in the CB/RT group confirms that the tumor oxygenation with carbogen was radiobiologically significant. Repeated tumor pO₂ measurements by EPR oximetry can provide temporal information that could be used to improve therapeutic outcomes by scheduling doses at times of improved tumor oxygenation.

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The study aimed to detect features of human serum proteome that were associated with exposure to ionizing radiation. The analyzed group consisted of 46 patients treated with radical radiotherapy for larynx cancer; patients were irradiated with total doses in a range from 51 to 72 Gy. Three consecutive blood samples were collected from each patient: before the start, 2 weeks after the start, and 4–6 weeks after the end of radiotherapy. The low-molecular-weight fraction of the serum proteome (2,000–13,000 Da) was analyzed by the MALDI-ToF mass spectrometry. Proteome profiles of serum samples collected before the start of radiotherapy and during the early stage of the treatment were similar. In marked contrast, mass profiles of serum samples collected several weeks after the end of the treatment revealed clear changes. We found that 41 out of 312 registered peptide ions changed their abundance significantly when serum samples collected after the final irradiation were compared with samples collected at the two earlier time points. We also found that abundances of certain serum peptides were associated with total doses of radiation received by patients. The results of this pilot study indicate that features of serum proteome analyzed by mass spectrometry have potential applicability as a retrospective marker of exposure to ionizing radiation.

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Our previous animal study had demonstrated that partial liver irradiation (IR) could stimulate regeneration in the protected liver, which supported the measurements adopted in radiotherapy planning for hepatocellular carcinoma. The purpose of this present study is to investigate whether cirrhotic liver repopulation could be triggered by partial liver IR. The cirrhosis was induced by thioacetamide (TAA) in rats. After cirrhosis establishment, TAA was withdrawn. In Experiment 1, only right-half liver was irradiated with single doses of 5 Gy, 10 Gy and 15 Gy, respectively. In Experiment 2, right-half liver was irradiated to 15 Gy, and the left-half to 2.5 Gy, 5 Gy and 7.5 Gy, respectively. The regeneration endpoints, including liver index (LI); mitotic index (MI); liver proliferation index (LPI); PCNA-labeling index (PCNA-LI); serum HGF, VEGF, TGF-α and IL-6, were evaluated on 0 day, 30-day, 60-day, 90-day, 120-day and 150-day after IR. Serum and in situ TGF-β1 were also measured. In both experimental groups, the IR injuries were sublethal, inducing no more than 9% animal deaths. Upon TAA withdrawal, hepatic regeneration decelerated in the controls. In Experiment 1 except for LI, all other regeneration parameters were significantly higher than those in controls for both right-half and left-half livers. In Experiment 2 all regeneration parameters were also higher compared with those in controls for both half livers. Serum HGF and VEGF were increased compared with that of controls. Both unirradiated and low dose-irradiated cirrhotic liver were able to regenerate triggered by sublethal partial liver IR and higher doses and IR to both halves liver triggered a more enhanced regeneration.

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The objective of our study was to describe the dose gradient characteristics of Linac-based stereotactic radiosurgery using Paddick's gradient index (GI) and to elucidate the factors influencing the GI value. Seventy-three plans for brain metastases using the dynamic conformal arcs were reviewed. The GI values were calculated at the 80% and 90% isodose surfaces (IDSs) and at the different target coverage IDSs (D99, D95, D90, and D85). The GI values significantly decreased as the target coverage of the reference IDS increased (the percentage of the IDS decreased). There was a significant inverse correlation between the GI values and target volume. The plans generated with the addition of a 1-mm leaf margin had worse GI values both at the D99 and D95 relative to those without leaf margin. The number and arrangement of arcs also affected the GI value. The GI values are highly sensitive to (1) the IDS selection variability for dose prescription or evaluation, (2) the target volume, and (3) the planning method. To objectively compare the quality of dose gradient between rival plans, it would be preferable to employ the GI defined at the reference IDS indicating the specific target coverage (e.g., D95), irrespective of the intended marginal dose. The modified GI (mGI), defined in this study, substituting the denominator of the original GI with the target volume, would be useful to compensate for the false superior GI value in cases of target over-coverage with the reference IDS and to objectively evaluate the dose gradient outside the target boundary.

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The atomic bombs in Hiroshima and Nagasaki led to two different types of radiation exposure; one was direct and brief and the other was indirect and persistent. The latter (so-called exposure to residual radiation) resulted from the presence of neutron activation products in the soil, or from fission products present in the fallout. Compared with the doses from direct exposures, estimations of individual doses from residual radiation have been much more complicated, and estimates vary widely among researchers. The present report bases its conclusions on radiation doses recorded in tooth enamel from survivors in Hiroshima. Those survivors were present at distances of about 3 km or greater from the hypocenter at the time of the explosion, and have DS02 estimated doses (direct exposure doses) of less than 5 mGy (and are regarded as control subjects). Individual doses were estimated by measuring CO₂^– radicals in tooth enamel with the electron spin resonance (ESR; or electron paramagnetic resonance, EPR) method. The results from 56 molars donated by 49 survivors provided estimated doses which vary from –200 mGy to 500 mGy, and the median dose was 17 mGy (25% and 75% quartiles are –54 mGy and 137 mGy, respectively) for the buccal parts and 13 mGy (25% and 75% quartiles: –49 mGy and 87 mGy, respectively) for the lingual parts of the molars. Three molars had ESR-estimated doses of 300 to 400 mGy for both the buccal and lingual parts, which indicates possible exposures to excess doses of penetrating radiation, although the origin of such radiation remains to be determined. The results did not support claims that a large fraction of distally-exposed survivors received large doses (e.g. 1 Gy) of external penetrating radiation resulting from residual radiation.

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The aim of this study was to examine biological effects of nitric oxide (NO) on radiosensitivity and chromosome aberrations in different phases of the cell cycle in human cancer cells with a wild-type p53 (wtp53) genotype. H1299/wtp53 cells were pre-treated with isosorbide dinitrate (ISDN) at different concentrations or pre-irradiated with a low dose of X-rays, and then exposed to a high dose of X-rays. Cell synchronization was achieved with serum starvation. Cellular radiosensitivity, cell cycle distributions, and chromosome aberrations were assayed with colony-forming assays, flow cytometry and chromosome banding techniques, respectively. After treatment with ISDN at a low concentration or after an exposure to 0.02 Gy of X-rays, radioresistance and a reduction in the number of chromosome aberrations were observed mainly 17.5 h after plating mitotic cells. This radioadaptation effect was observed during a clearly shortened G₂/M phase and a slightly prolonged S phase. In contrast, in the presence of a high concentration of ISDN, radiosensitization and the enhancement of chromosome aberrations were detected principally 17.5 h after plating mitotic cells, and this radiosensitization was observed during a significantly prolonged G₂/M phase and a slightly shortened S phase. A range of concentrations of NO induced opposing effects on radiosensitivity and chromosome aberrations in human non-small cell lung cancer cells bearing wtp53 gene status, and these different effects produced by NO depended on the cell cycle phase.

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Vitamin D has a selective radio and chemosensitizing effect on tumor cells. In vitro and in vivo studies have shown that vitamin D inhibits collagen gel construction, induces type II pneumocyte proliferation and surfactant synthesis in the lungs, and decreases vascular permeability caused by radiation. The aim of this experimental study was to determine if vitamin D has a protective effect against radiation-induced pulmonary damage. Adult Wistar rats were divided into 4 groups. Group 1 was comprised of control animals. Group 2, which was administered 0.25 μg/kg/day of vitamin D3 for 8 weeks, was the vitamin D control group. Rats in groups 3 and 4 were given 20 Gy right hemithorax radiotherapy, and in addition group 4 was given vitamin D3 treatment, which began the day before the radiotherapy and continued for 8 weeks. At the 8^th and the 12^th weeks of the study 4 rats from each group were sacrificed. Right lungs were dissected for light and electron microscopic study. The electron microscopy examinations revealed statistically significant differences between group 3 and 4, and in group 4 there was less interstitial inflammation and collagen deposition, and the alveolar structure and the cells lining the alveolar walls were protected. These results confirm that vitamin D has a protective effect against radiation-induced pulmonary toxicity. These findings should be evaluated with further clinical studies.

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Growing evidence has demonstrated that, as an endogenous signaling gasotransmitter, hydrogen sulfide (H₂S) plays an important role in regulating numerous biological functions. The role of H₂S in hypoxia-induced radioresistance on hepatoma cells was investigated in the present work. Results showed that, when HepG2 cells were maintained in hypoxia circumstances for 4 h, the cellular radioresistance was extensively increased so that the oxygen enhancement ratio of the survival fraction approached 2.68. Under this hypoxic condition, when the cells were treated with DL-propargylglycine (PPG) and aminooxyacetic acid (AOAA), a specific inhibitor of H₂S synthase of cystathionine-γ-lyase (CSE) and cystathionine-β-synthase (CBS) respectively, radiation responses including cell killing, micronuclei (MN) formation, and caspase-3 activity were significantly enhanced. However, treatment of cells with low concentrations of NaHS (≤ 100 μM) protected cells from these radiation damages. Western bolting assay showed that CSE and CBS were over-expressed in the irradiated hypoxic cells in a dose dependent manner. Moreover, when the hypoxic HepG2 cells were treated with NaHS together with glibenclamide, a specific inhibitor of K⁺_ATP channels, the role of exogenous H₂S in radioprotection was partly eliminated. This study demonstrated that H₂S contributed to hypoxia-induced radioresistance probably via the opening of K⁺_ATP channels, which suggests that the endogenous H₂S synthase could be a potential radiotherapeutic target for a hypoxic tumor.

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During the Chernobyl Nuclear Power Plant (CNPP) accident on 26 April 1986, large amounts of radionuclides were released and spread to vast areas. Inhabitants residing around CNPP have been exposed to external and internal irradiation due to the long half-life of ¹³⁷Cs (30 years). In this study, we screened for internal whole-body ¹³⁷Cs concentration using a whole-body counter in the Zhitomir state of Ukraine. The total number of participants was 144,972 (96,149 females and 48,823 males). The median body burden of ¹³⁷Cs per body weight decreased from 1996 to 2008. In particular, after 2003, more than half of subjects had internal exposure doses below the detectable level. A weak seasonal effect was found in measurement data from 1997 to 1999, but no such effects were observed in later years. We also calculated annual dose for each year and confirmed that doses have been decreasing gradually. In particular, after 2003, the annual effective dose decreased to 0.1 mSv y^–1 for 95% of the participants. Only two persons were found to have received more than 5 mSv y^–1 since 2007. Although the health effects of ¹³⁷Cs body burden due to the Chernobyl accident remain uncertain, further screening is needed to monitor the health status and to allay the anxiety of inhabitants in the contaminated areas around CNPP.

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Intracavitary brachytherapy using tandem and ovoids is an important component of definitive treatment for cervical cancer. In the present study, we analyzed the dose-volume histograms (DVHs) of the tumor volume and organs at risk including the sigmoid colon by CT-based treatment planning for high dose rate (HDR) intracavitary brachytherapy (ICBT) in cervical cancer. Seventeen patients with carcinoma of the cervix uteri were treated with external beam radiotherapy plus concurrent chemotherapy. For brachytherapy, the planning procedure started by performing a conventional plan which prescribed a dose of 6.5–7 Gy per fraction to point A, then optimized the dose based on CT imaging. Volumes and DVHs were calculated for the HR-CTV, bladder, rectum and sigmoid colon. The mean BED_2Gy total doses of post-optimized plans of HR-CTV, bladder, rectum and sigmoid colon were: 89.6, 94.1, 74.0 and 69.8 Gy, respectively. For conventional plans, the calculated mean BED_2Gy total doses of HR-CTV, bladder, rectum and sigmoid colon were 92.2, 120.1, 75.7 and 78.3 Gy, respectively. This study showed statistical significant higher BED_2Gy total doses for bladder and sigmoid colon (p < 0.001) using conventional plans versus post-optimized, CT-based plans, while no difference between HR-CTV and rectum BED_2Gy total doses could be detected. After a median follow-up of nineteen months, all seventeen patients had a clinical complete response. Two patients developed distant metastasis. Compared with conventional treatment, CT based brachytherapy planning was very effective in reducing doses to OARs, especially bladder and sigmoid colon whilst maintaining a high therapeutic dose for tumor target volumes in the treatment of cervical carcinoma.

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The study was performed to evaluate radiotherapy for patients with intramedullary spinal cord metastasis (ISCM) and to identify the clinical features of ISCM. The subjects were 18 patients (8 men, 10 women) with ISCM who underwent radiotherapy between September 2002 and February 2008. The primary lesions were lung cancer in 8 patients (2 small cell, 6 non-small cell), breast cancer in 6, malignant melanoma in 2, renal cell carcinoma in 1, and rectal cancer in 1 patient. Diagnosis, symptoms and survival of these patients were compared with those for 544 patients with vertebral metastases who underwent radiotherapy at the same institute between September 2002 and November 2006. In the 18 patients with ISCM, the 6-month survival rate after radiotherapy was 36% and the median survival period was 4.0 months. Ten patients had neurological improvement or pain relief after radiotherapy. Brain metastases were six fold more frequent in the patients with ISCM than in those with vertebral metastasis [89% vs. 15%, p = 0.001]. At the time of radiotherapy, back pain in patients with vertebral metastasis was more frequent [97% vs. 33%, p = 0.001] but neurological deficits were less common [24% vs. 100% , p = 0.001]. Most ISCM cases were diagnosed by contrast-enhanced MRI, with detection by contrast-enhanced CT in only 3/18 cases (17%). ISCM has a poor prognosis and most patients have neurological deficits that impair quality of life. Early diagnosis by MRI is important for suspected ISCM to allow initiation of radiotherapy before development of neurological deficits.

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In this study, a novel combination treatment of armed oncolytic adenovirus expressing interleukin 12 (IL-12) and granulocyte-macrophage colony-stimulating factor (GM-CSF) with radiation was investigated for antitumor and antimetastatic effect in a murine hepatic cancer (HCa-I) model. Tumor bearing syngeneic mice were treated with radiation, armed oncolytic virus Ad-ΔE1Bmt7 (dB7) expressing both IL-12 and GM-CSF (armed dB7), or a combination of both. The adenovirus was administered by intratumoral injection 1 × 10⁸ PFU per tumor in 50 μl of PBS four times every other day. Tumor response to treatment was determined by a tumor growth delay assay. Metastatic potential was evaluated by a lung metastasis model. To understand the underlying mechanism, the level of apoptosis was examined as well as the change in microvessel density and expression of immunological markers: CD4+, CD8+ and Cd11c. The combination of armed dB7 and radiation resulted in significant growth delay of murine hepatic cancer, HCa-1, with an enhancement factor of 4.3. The combination treatment also resulted in significant suppression of lung metastasis. Increase of apoptosis level as well as decrease of microvessel density was shown in the combination treatment, suggesting an underlying mechanism for the enhancement of antitumor effect. Expression of immunological markers: CD4+, CD8+ and Cd11c also increased in the combination treatment. This study showed that a novel combination treatment of radiotherapy with armed oncolytic adenovirus expressing IL-12 and GM-CSF was effective in suppressing primary tumor growth.

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Purpose: To determine the results and long-term changes in radiation toxicity of stage I-II buccal mucosa cancer patients treated by low-dose-rate (LDR) brachytherapy with ¹⁹⁸Au grains. Materials and Methods: A total of 133 stage I-II buccal mucosa carcinomas patients received ¹⁹⁸Au grain implantation brachytherapy between January 1982 and July 2005: 75 of them were treated by ¹⁹⁸Au grain implantation alone and 58 were treated by ¹⁹⁸Au implantation in combination with external irradiation. The average ¹⁹⁸Au-grain dose was 70 Gy in 7 days. Gross tumor areas ranged from 2.4 cm² to 9 cm², and the clinical target areas ranged from 6 cm² to 15 cm². Results: The follow-up periods ranged from 3 months to 20 years (mean: 5 years 11 months and median: 5 years 1 months). Failure at the site of the primary lesion occurred in 17 patients. Post-treatment mucosal ulceration developed in 15 patients, and all were cured within 25 months by conservative treatment. Osteoradionecrosis was diagnosed in 8 patients, but only one patient required surgical treatment. No severe complications or aggravation of complications developed more than 10 years after treatment. Conclusions: The results of low-dose-rate (LDR)-brachytherapy (BT) alone and LDR-BT in combination with external irradiation at a total dose of 25 Gy were acceptable from the standpoint of cure rate and QOL.

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To evaluate the intra- and interfractional gastric motion using repeated CT scans, six consecutive patients with gastric lymphoma treated at our institution between 2006 and 2008 were included in this study. We performed a simulation and delivered RT before lunch after an overnight fast to minimize the stomach volume. These patients underwent repeated CT scanning at mild inhale and exhale before their course of treatment. The repeated CT scans were matched on bony anatomy to the planning scan. The center of stomach was determined in the X (lateral), Y (superior-inferior), and Z (ventro-dorsal) coordinate system to evaluate the intra- and interfractional motion of the stomach on each CT scan. We then calculated the treatment margins. Each patient was evaluated four to five times before their course of RT. The average intrafractional motions were –12.1, 2.4 and 4.6 mm for the superior-inferior (SI), lateral (LAT), and ventro-dorsal (VD) direction. The average interfractional motions of the center of the stomach were –4.1, 1.9 and 1.5 mm for the SI, LAT and VD direction. The average of the vector length was 13.0 mm. The systematic and random errors in SI direction were 5.1, and 4.6 mm, respectively. The corresponding figures in LAT and VD directions were 10.9, 5.4, 10.0, and 6.5 mm, respectively. Thus, the 15.9, 31.0 and 29.6 mm of margins are required for the SI, LAT, and VD directions, respectively. We have demonstrated not only intrafractional stomach motion, but also interfractional motion is considerable.

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This study aims to assess the efficacy and toxicity of definitive radiotherapy for early-stage endometrial carcinoma. The correlation between CT-based dosimetric parameters and clinical outcomes is also evaluated. Between 2002 and 2006, 10 medically inoperable patients with T1-2 endometrial carcinoma were treated with radiotherapy alone. A combination of external beam radiotherapy (EBRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT) was used for 9 patients, and one was treated with HDR-ICBT alone. Dose prescription of HDR-ICBT was determined in reference to CT images at brachytherapy, and a total dose of 22–24 Gy in 4 fractions was delivered to the outer perimeter of the uterine corpus. Dose-volume parameters of the gross tumor volume (GTV), clinical target volume (CTV), and organs at risk were assessed retrospectively using the dose-volume histograms derived from the CT image-based treatment planning system. After a median follow-up of 55 months, 9 patients were alive without evidence of recurrence. One patient died from liver cirrhosis 17 months after radiotherapy. Severe acute and late toxicities were not observed in any of the patients. Average minimum dose to 90% of GTV and CTV (D90) was 88.0 and 45.9 Gy_EQD2, respectively. The minimum dose delivered to 2 cc of the most irradiated volumes of the rectum and sigmoid colon (D_2cc) was 78.9 and 65.9 Gy_EQD2, respectively. These patients developed Grade 1 late complications. In this study, stage I–II endometrial carcinoma was well-controlled locally with minimum late toxicity by radiotherapy alone with HDR-ICBT. 3D image-based brachytherapy may potentially deliver a sufficiently high dose to the whole tumor without significant increase in dose to surrounding normal tissues.

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The objectives of this study were to determine the tolerability of combined use of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) with external beam radiation therapy (EBRT) and to access the efficacy in patients with locally advanced or metastatic bladder cancer. From December 2000 to November 2010, 30 eligible patients were enrolled in this study. After receiving one cycle of MVAC treatment, all patients received EBRT with a half dose of MVAC treatment followed by two more cycles of chemotherapy. A standard fractionation with daily dose of 1.8–2.0 Gy was used, with the total dose up to 60 Gy over 5–6 weeks. The four-field box technique was utilized for radiation fields. Thirteen patients (43%) had complete response and 11 (37%) had partial response, with an overall response rate of 80%. The median overall survival and progression-free survival was 25.5 months and 12.8 months, respectively. In the complete-response patients, median overall survival was 37.1 months. Grade 3 or 4 neutropenia occurred in 25 patients (83%), but there were no severe infections. One patient (3%) had hemorrhagic radiation cystitis. There were no treatment-related deaths. Combined use of MVAC treatment with EBRT is a favorable therapeutic option for patients with advanced or metastatic bladder carcinoma. Given the safety and benefit profile found in this study, appropriate case selection is warranted in the future.

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Computed tomography (CT)/magnetic resonance imaging (MRI) fusion is considered to be the best method for postimplant dosimetry of permanent prostate brachytherapy; however, it is inconvenient and costly. In T2*-weighted image (T2*-WI), seeds can be easily detected without the use of an intravenous contrast material. We present a novel method for postimplant dosimetry using T2*-WI/T2-weighted image (T2-WI) fusion. We compared the outcomes of T2*-WI/T2-WI fusion-based and CT/T2-WI fusion-based postimplant dosimetry. Between April 2008 and July 2009, 50 consecutive prostate cancer patients underwent brachytherapy. All the patients were treated with 144 Gy of brachytherapy alone. Dose-volume histogram (DVH) parameters (prostate D90, prostate V100, prostate V150, urethral D10, and rectal D2cc) were prospectively compared between T2*-WI/T2-WI fusion-based and CT/T2-WI fusion-based dosimetry. All the DVH parameters estimated by T2*-WI/T2-WI fusion-based dosimetry strongly correlated to those estimated by CT/T2-WI fusion-based dosimetry (0.77 ≤ R ≤ 0.91). No significant difference was observed in these parameters between the two methods, except for prostate V150 (p = 0.04). These results show that T2*-WI/T2-WI fusion-based dosimetry is comparable or superior to MRI-based dosimetry as previously reported, because no intravenous contrast material is required. For some patients, rather large differences were observed in the value between the 2 methods. We thought these large differences were a result of seed miscounts in T2*-WI and shifts in fusion. Improving the image quality of T2*-WI and the image acquisition speed of T2*-WI and T2-WI may decrease seed miscounts and fusion shifts. Therefore, in the future, T2*-WI/T2-WI fusion may be more useful for postimplant dosimetry of prostate brachytherapy.

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