Development and Validation of a Preoperative Nomogram for Endoscopic Management Decision Making in Upper Urinary Tract Urothelial Carcinoma.

OBJECTIVE: We aimed to develop and validate a preoperative nomogram that predicts low-grade, non-muscle invasive upper urinary tract urothelial carcinoma (LG-NMI UTUC), thereby aiding in the accurate selection of endoscopic management (EM) candidates. METHODS: This was a retrospective study that included 454 patients who underwent radical surgery (Cohort 1 and Cohort 2), and 26 patients who received EM (Cohort 3). Utilizing a multivariate logistic regression model, a nomogram predicting LG-NMI UTUC was developed based on data from Cohort 1. The nomogram's accuracy was compared with conventional European Association of Urology (EAU) and National Comprehensive Cancer Network (NCCN) models. External validation was performed using Cohort 2 data, and the nomogram's prognostic value was evaluated via disease progression metrics in Cohort 3. RESULTS: In Cohort 1, multivariate analyses highlighted the absence of invasive disease on imaging (odds ratio [OR] 7.04; p = 0.011), absence of hydronephrosis (OR 2.06; p = 0.027), papillary architecture (OR 24.9; p < 0.001), and lack of high-grade urine cytology (OR 0.22; p < 0.001) as independent predictive factors for LG-NMI disease. The nomogram outperformed the two conventional models in predictive accuracy (0.869 vs. 0.759-0.821) and exhibited a higher net benefit in decision curve analysis. The model's clinical efficacy was corroborated in Cohort 2. Moreover, the nomogram stratified disease progression-free survival rates in Cohort 3. CONCLUSION: Our nomogram ( https://kmur.shinyapps.io/UTUC_URS/ ) accurately predicts LG-NMI UTUC, thereby identifying suitable candidates for EM. Additionally, the model serves as a useful tool for prognostic stratification in patients undergoing EM.

Assessing Therapeutic Response to Radium-223 with an Automated Bone Scan Index among Metastatic Castration-Resistant Prostate Cancer Patients: Data from Patients in the J-RAP-BSI Trial.

To evaluate the usefulness of change in the automated bone scan index (aBSI) value derived from bone scintigraphy findings as an imaging biomarker for the assessment of treatment response and survival prediction in metastatic castration-resistant prostate cancer (mCRPC) patients treated with Ra-223. This study was a retrospective investigation of a Japanese cohort of 205 mCRPC patients who received Ra-223 in 14 hospitals between July 2016 and August 2020 and for whom bone scintigraphy before and after radium-223 treatment was available. Correlations of aBSI change, with changes in the serum markers alkaline phosphatase (ALP) and prostate-specific antigen (PSA) were evaluated. Additionally, the association of those changes with overall survival (OS) was assessed using the Cox proportional-hazards model and Kaplan-Meier curve results. Of the 205 patients enrolled, 165 (80.5%) completed six cycles of Ra-223. Following treatment, ALP decline (%ALP < 0%) was noted in 72.2% (148/205), aBSI decline (%aBSI < 0%) in 52.7% (108/205), and PSA decline (%PSA < 0%) in 27.8% (57/205). Furthermore, a reduction in both aBSI and ALP was seen in 87 (42.4%), a reduction in only ALP was seen in 61 (29.8%), a reduction in only aBSI was seen in 21 (10.2%), and in both aBSI and ALP increasing/stable (≥0%) was seen in 36 (17.6%) patients. Multiparametric analysis showed changes in PSA [hazard ratio (HR) 4.30, 95% confidence interval (CI) 2.32-8.77, p < 0.0001], aBSI (HR 2.22, 95%CI 1.43-3.59, p = 0.0003), and ALP (HR 2.06, 95%CI 1.35-3.14, p = 0.0008) as significant prognostic factors for OS. For mCRPC patients treated with Ra-223, aBSI change is useful as an imaging biomarker for treatment response assessment and survival prediction.

Novel nomogram developed for determining suitability of metastatic castration-resistant prostate cancer patients to receive maximum benefit from radium-223 dichloride treatment-Japanese Ra-223 Therapy in Prostate Cancer using Bone Scan Index (J-RAP-BSI) Trial.

PURPOSE: To develop a novel nomogram for determining radium-223 dichloride (Ra-223) treatment suitability for metastatic castration-resistant prostate cancer (mCRPC) patients. METHODS: This Japanese Ra-223 Therapy in Prostate Cancer using Bone Scan Index (J-RAP-BSI) Trial was a retrospective multicenter investigation enrolled 258 mCRPC patients in Japan with Ra-223 treatment between June 2016 and August 2020, with bone scintigraphy findings before treatment, clinical data, and survival outcome available. A nomogram was constructed using prognostic factors for overall survival (OS) based on a least absolute shrinkage and selection operator Cox regression model. A sub-analysis was also conducted for patients meeting European Medicines Agency (EMA) guidelines. RESULTS: Within a median of 17.4 months after initial Ra-223 treatment, 124 patients (48.1%) died from prostate cancer. Predictive factors included (1) sum of prior treatment history (score 0, never prior novel androgen receptor-targeted agents (ARTA) therapy, never prior taxane-based chemotherapy, and ever prior bisphosphonate/denosumab treatment), (2) Eastern Cooperative Oncology Group (ECOG) performance status, (3) prostate-specific antigen doubling time (PSADT), (4) hemoglobin, (5) lactate dehydrogenase (LDH), and (6) alkaline phosphatase (ALP) levels, and (7) automated bone scan index (aBSI) value based on bone scintigraphy. The nomogram using those factors showed good discrimination, with apparent and optimism-corrected Harrell's concordance index values of 0.748 and 0.734, respectively. Time-dependent area under the curve values at 1, 2, and 3 years were 0.771, 0.818, and 0.771, respectively. In 227 patients meeting EMA recommendation, the nomogram with seven factors showed good discrimination, with apparent and optimism-corrected Harrell's concordance index values of 0.722 and 0.704, respectively. Time-dependent area under the curve values at 1, 2, and 3 years were 0.747, 0.790, and 0.759, respectively. CONCLUSION: This novel nomogram including aBSI to select mCRPC patients to receive Ra-223 with significantly prolonged OS possibility was found suitable for assisting therapeutic decision-making, regardless of EMA recommendation.

Two cases of 18F-FDG-PET/CT positive Schloffer tumor following curative surgery of colon cancer.

We report two cases of Schloffer tumor that required resection after radical colon cancer surgery because of suspected lymph node recurrence on contrast-enhanced (CE) CT and 18F-FDG-PET/CT. Case1 is a 69-year-old man with sigmoid colon cancer pStage IIA, and case2 is a 61-year-old man with descending colon cancer pStage IIIB.

Carcinoma of Unknown Original Identified as Renal Cell Carcinoma by 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Scan: A Report of Two Cases.

Imaging is useful in identifying the primary site of an unknown primary cancer, and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is an excellent imaging modality for identifying the primary lesion. However, a potential limitation is that 18F-FDG is physiologically excreted from the kidneys, thus masking renal lesions. In this report, we describe two cases of cancer of unknown origin that were detected as originating from renal cancer on 18F-FDG PET/CT. Both cases showed abnormal nodular accumulation of 18F-FDG in the kidney, which can be distinguished from the physiological excretion of 18F-FDG in the urinary tract. It is clinically crucial to be able to confirm the possibility of renal cancer, and careful observation of the urinary tract with 18F-FDG PET/CT can be useful.

Efficacy of Combination Therapy with Lenvatinib and Radioactive Iodine in Thyroid Cancer Preclinical Model.

Patients with differentiated thyroid cancer (DTC) usually have good prognosis, while those with advanced disease have poor clinical outcomes. This study aimed to investigate the antitumor effects of combination therapy with lenvatinib and 131I (CTLI) using three different types of DTC cell lines with different profiling of sodium iodide symporter (NIS) status. The radioiodine accumulation study revealed a significantly increased radioiodine uptake in K1-NIS cells after lenvatinib treatment, while there was almost no uptake in K1 and FTC-133 cells. However, lenvatinib administration before radioiodine treatment decreased radioiodine uptake of K1-NIS xenograft tumor in the in vivo imaging study. CTLI synergistically inhibited colony formation and DTC cell migration, especially in K1-NIS cells. Finally, 131I treatment followed by lenvatinib administration significantly inhibited tumor growth of the NIS-expressing thyroid cancer xenograft model. These results provide important clinical implications for the combined therapy that lenvatinib should be administered after 131I treatment to maximize the treatment efficacy. Our synergistic treatment effects by CTLI suggested its effectiveness for RAI-avid thyroid cancer, which retains NIS function. This potential combination therapy suggests a powerful and tolerable new therapeutic strategy for advanced thyroid cancer.

Self-organizing map improves understanding on the hydrochemical processes in aquifer systems.

The holistic understanding of hydrochemical features is a crucial task for management and protection of water resources. However, it is challenging for a complex region, where multiple factors can cause hydrochemical changes in studied catchment. We collected 208 groundwater samples from such region in Kumamoto, southern Japan to explicitly characterize these processes by applying machine learning technique. The analyzed groundwater chemistry data like major cations and anions were fed to the self-organizing map (SOM) and the results were compared with classical classification approaches like Stiff diagram, standalone cluster analysis and score plots of principal component analysis (PCA). The SOM with integrated application of clustering divided the data into 11 clusters in this complex region. We confirmed that the results provide much greater details for the associated hydrochemical and contamination processes than the traditional approaches, which show quite good correspondence with the recent high resolution hydrological simulation model and aspects from geochemical modeling. However, the careful application of the SOM is necessary for obtaining accurate results. This study tested different normalization approaches for selecting the best SOM map and found that the topographic error (TE) was more important over the quantization error (QE). For instance, the lower QE obtained from min-max and log normalizations showed problems after clustering the SOM map, since the QE did not confirm the topological preservation. In contrast, the lowest TE obtained from Z-transformation data showed better spatial matching of the clusters with relevant hydrochemical characteristics. The results from this study clearly demonstrated that the SOM is a helpful approach for explicit understanding of the hydrochemical processes on reginal scale that may capably facilitate better groundwater resource management.

Estimation of the degree of surgical difficulty anticipated for pancreatoduodenectomy: Preoperative and intraoperative factors.

BACKGROUND: Pancreatoduodenectomy (PD) is a technically complex procedure. Preoperative anticipation of the degree of difficulty could contribute to patient safety during trainee surgical education. METHODS: We prospectively administered a questionnaire to the chief surgeon after each PD performed between 2016 and 2018 at our institution (99 consecutive patients). The surgeon rated the difficulty of the procedure; we then analyzed this information against perioperative data. RESULTS: The difficulty of PD was ranked as simple (29.3%), moderate (40.4%), or difficult (30.3%). The difficult procedures required an operative time of 2 h longer than the simple procedures and involved an additional 800 mL of intraoperative blood loss. Postoperative complications were similar in all groups. Multivariate analysis revealed that an unrecognized tissue plane for dissection was an independent determinant of a difficult PD (odds ratio [OR]: 89.2, 95% confidence interval [CI]: 9.2-861.2; P < .001). Independent predictors of a difficult PD were a pretreatment status of borderline resectable or unresectable (OR: 21.9, CI: 5.3-90.6; P < .001) and cholangitis during the preoperative period (OR: 4.1, CI: 1.3-13.0; P = .017). CONCLUSIONS: Surgeons deem the PD procedure to be difficult when the proper tissue plane for dissection is unrecognized. Preoperative assessment of the anticipated difficulty could contribute to better operative management.

A comparison of HER2/neu accumulations of Ga-67-labeled anti-HER2 antibody with chemically and site-specifically conjugated bifunctional chelators.

Monoclonal antibodies (mAb) developed to target specific cancers have achieved considerable success to date. To further enhance therapeutic efficacy, monoclonal antibodies may be conjugated with a cytotoxic drug or radioisotope. We present the development of a new method based on site-specific conjugation (SSC) for targeting HER2. The study design involves a comparison of the accumulation of Ga-67-labeled anti-HER2 antibodies with SSC (SSC-mAb) versus conventional chemical conjugation (Chem-mAb) in HER2-positive tumors. In vitro, the HER2-binding capacity of SSC-mAb and Chem-mAb was comparable. However, in vitro, the rate of tumor accumulation increased gradually with SSC-mAb not only in the tumors but also in the blood and other organs. The SSC may improve targeted antigen-specific cancer radioimmunotherapy and may, due to higher retention, reduce the amount of treatment required.

Impact of four-dimensional cone-beam computed tomography on target localization for gastric mucosa-associated lymphoid tissue lymphoma radiotherapy: reducing planning target volume.

BACKGROUND: Radiotherapy of gastric mucosa-associated lymphoid tissue (MALT) lymphoma should be delivered to the entire stomach with planning target volume (PTV) that accounts for variations in stomach volume, respiratory movement, and patient set-up error. In this study, we evaluated whether the use of four-dimensional cone-beam computed tomography (4D-CBCT) reduces the PTV. METHODS: Eight patients underwent radiotherapy with 15 fractions of gastric MALT lymphoma using 4D-CBCT. PTV structures of 5-30 mm margins (5 mm intervals) from the clinical target volume (CTV) delineated based on the 4D-CT images (CTV-4D) were generated. For the target localization, we performed matching based on skin marking (skin matching), bone anatomy (bone matching), and stomach anatomy (4D soft-tissue matching) based on registration between planning CT and 4D-CBCT images from 10 phases. For each patient, we calculated the covering ratio (CR) of the stomach with variable PTV structures, based on the 4D-CBCT images, with a total of 150 phases [CR (%) = (number of covering phases/150 phases) × 100], for three target localization methods. We compared the CR values of the different target localization methods and defined the PTV with an average CR of ≥ 95% for all patients. RESULTS: The average CR for all patients increased from 17.9 to 100%, 19.6 to 99.8%, and 33.8 to 100%, in the skin, bone, and 4D soft-tissue matchings, respectively, as the PTV structures increased from 5 to 30 mm. The CR obtained by 4D soft-tissue matching was superior to that obtained by skin (P = 0.013) and bone matching (P = 0.008) for a PTV structure of 15 mm margin. The PTV required an additional margin of 20 mm (average CR: 95.2%), 25 mm (average CR: 99.1%), and 15 mm (average CR: 98.0%) to CTV-4D for the skin, bone, and 4D soft-tissue matchings, respectively. CONCLUSIONS: This study demonstrates that the use of 4D-CBCT reduces the PTV when applying 4D soft-tissue matching, compared to skin and bone matchings. Additionally, bone matching does not reduce the PTV as compared with traditional skin matching.

Combination therapy with lenvatinib and radiation significantly inhibits thyroid cancer growth by uptake of tyrosine kinase inhibitor.

Although surgical treatment cures >90% of differentiated thyroid cancer (DTC) patients, the remaining patients, including advanced DTC cases, have poor clinical outcomes. These patients with inoperable disease have only two choices of radioactive iodine therapy and tyrosine kinase inhibitors such as lenvatinib, which have a high incidence of treatment-related adverse events and can only prolong progression free survival by approximately 5-15 months. In this study, we investigated the antitumor effects of combination therapy with lenvatinib and radiation (CTLR) for DTC. CTLR synergistically inhibited cell replication and colony formation in vitro and tumor growth in nude mice without apparent toxicities and suppressed the expression of proliferation marker (Ki-67). CTLR also induced apoptosis and G2/M phase cell cycle arrest. Moreover, quantitative analysis of the intracellular uptake of lenvatinib using liquid chromatography and mass spectrometry demonstrated that intracellular uptake of lenvatinib was significantly increased 48 h following irradiation. These data suggest that increased membrane permeability caused by irradiation increases the intracellular concentration of levatinib, contributing to the synergistic effect. This mechanism-based potential of combination therapy suggests a powerful new therapeutic strategy for advanced thyroid cancer with fewer side effects and might be a milestone for developing a regimen in clinical practice.

A Novel Approach for Investigating Upper Airway Hyperresponsiveness Using Micro-CT in Eosinophilic Upper Airway Inflammation such as Allergic Rhinitis Model.

Airway hyperresponsiveness (AHR) has been proposed as a feature of pathogenesis of eosinophilic upper airway inflammation such as allergic rhinitis (AR). The measurement system for upper AHR (UAHR) in rodents is poorly developed, although measurements of nasal resistance have been reported. Here we assessed UAHR by direct measurement of swelling of the nasal mucosa induced by intranasal methacholine (MCh) using micro-computed tomography (micro-CT). Micro-CT analysis was performed in both naïve and ovalbumin-induced AR mice following intranasal administration of MCh. The nasal cavity was segmented into two-dimensional horizontal and axial planes, and the data for nasal mucosa were acquired for the region of interest threshold. Then, a ratio between the nasal mucosa area and nasal cavity area was calculated as nasal mucosa index. Using our novel method, nasal cavity structure was clearly identified on micro-CT, and dose-dependent increased swelling of the nasal mucosa was observed upon MCh treatment. Moreover, the nasal mucosa index was significantly increased in AR mice compared to controls following MCh treatment, while ovalbumin administration did not affect swelling of the nasal mucosa in either group. This UAHR following MCh treatment was completely reversed by pretreatment with glucocorticoids. This novel approach using micro-CT for investigating UAHR reflects a precise assessment system for swelling of the nasal mucosa following MCh treatment; it not only sheds light on the mechanism of AR but also contributes to the development of new therapeutic drugs in AR patients.

[Feasibility and Safety of Dexmedetomidine Sedation in Transarterial Embolization for Hepatocellular Carcinoma with Hepatitis C-Related Cirrhosis].

BACKGROUND: Dexmedetomidine (Precedex®)is an agonist of a2-adrenergic receptors in certain parts of the brain. It was approved for "procedural sedation in the non-intubation in under local anesthesia" in June 2013 in Japan. However, because of metabolism delay, dexmedetomidine has to be administered carefully to patients with liver dysfunction. PURPOSE: To evaluate the feasibility and safety of sedation using dexmedetomidine in percutaneous arterial chemoembolization for hepatocellular carcinoma with liver dysfunction. METHODS: Thirty consecutive cases of percutaneous arterial chemoembolization for hepatocellular carcinoma with hepatitis C-related cirrhosis(male, 23; female, 7; age, 74±5.9; weight, 62.7±12.3 kg; Child-Pugh A, 23; Child-Pugh B, 7)were analyzed retrospectively. Dexmedetomidine was administered at 3 mg/kg/h for 15 minutes as the initial loading dose and at 0.4 mg/kg/h as the maintenance dose. The sedation level was evaluated using the Ramsay sedation scale. RESULTS: In 30 of 30 cases, percutaneous arterial chemoembolization therapy could be performed with dexme- detomidine sedation. In 27 of 30 cases, the procedure was completed with the maintenance dose of 0.4 mg/kg/h. In 3 of 30 cases, the maintenance dose was increased to 0.6 mg/kg/h because of patient body motion. The mean administration time of dexmedetomidine was 82±30 minutes. The level of sedation measured with the Ramsay sedation scale at the end of the procedure was 3 points in 29 cases and 5 points in one case. Adverse events occurred in 3 of 30 cases. Intravenous drip leakage occurred in one case, vertigo occurred in one case, and vomiting occurred in one case. There were no adverse events requiring treatment. CONCLUSION: Sedation with dexmedetomidine in percutaneous arterial chemoembolization for hepatocellular carcinoma with liver dysfunction was feasible and safe.

Balloon-Occluded Antegrade Transvenous Sclerotherapy to Treat Rectal Varices: A Direct Puncture Approach to the Superior Rectal Vein Through the Greater Sciatic Foramen Under CT Fluoroscopy Guidance.

Rectal varices occur in 44.5 % of patients with ectopic varices caused by portal hypertension, and 48.6 % of these patients are untreated and followed by observation. However, bleeding occurs in 38 % and shock leading to death in 5 % of such patients. Two patients, an 80-year-old woman undergoing treatment for primary biliary cirrhosis (Child-Pugh class A) and a 63-year-old man with class C hepatic cirrhosis (Child-Pugh class A), in whom balloon-occluded antegrade transvenous sclerotherapy was performed to treat rectal varices are reported. A catheter was inserted by directly puncturing the rectal vein percutaneously through the greater sciatic foramen under computed tomographic fluoroscopy guidance. In both cases, the rectal varices were successfully treated without any significant complications, with no bleeding from rectal varices after embolization.

The effect of radiation exposure on multidrug resistance: in vitro and in vivo studies using non-small lung cancer cells.

BACKGROUND: Technetium-99m methoxyisobutylisonitrile (Tc MIBI) is a substrate with the same uptake kinetics as doxorubicin. Multidrug resistance (MDR) is a mechanism that impedes chemotherapy of non-small cell lung cancer (NSCLC). We examined the effect of radiation exposure on MDR in NSCLC and the synergy between an MDR modulator, GG918, and radiation, using (99m)Tc MIBI in vitro and doxorubicin in vivo. METHODS: In vitro NSCLC cells (H1299) were exposed to radiation (3-, 6-, and 9-Gy-irradiated groups) alongside a not-irradiated (0 Gy) group. Technetium-99 metastable methoxyisobutylisonitrile ((99m)Tc MIBI) was administered to cell suspensions at 48 h after irradiation. Cell radioactivity was measured, and C in/C out ratios were calculated and compared. NSCLC cells were also subcutaneously transplanted into the left thigh of nude mice, which were subsequently raised for 2 weeks. Two groups of mice were used: mice exposed to irradiation (9-Gy-irradiated) and those that were not (not-irradiated). Doxorubicin was administered through the caudal vein at 48 h after the irradiation. Using an in vivo imaging system, intratumoural photon counts were measured. To determine the synergy between the MDR modulator and 3- or 6-Gy irradiation, the final GG918 concentration was determined: 0.1 µM (N-H, 3-H, and 6-H groups), 0.001 µM (N-L, 3-L, and 6-L groups), and 0 µM (N-0, 3-0, and 6-0 groups). C in/C out ratios were calculated and compared among the groups. RESULTS: C in/C out after 6- or 9-Gy irradiation was significantly higher than that of the not-irradiated group (0 Gy). In vivo, fluorescence photon counts were significantly higher in the tumours of 9-Gy-irradiated mice, up to 270 min after administration of doxorubicin, as compared to the not-irradiated mice. The C in/C out ratio in the N-H, 3-H, and 6-H groups was significantly higher than that in the N-0, 3-0, and 6-0 groups. There was no significant difference between C in/C out in the N-L group and that of the N-0 group. However, the C in/C out ratio in the 3-L and 6-L groups was significantly higher than that in the 3-0 and 6-0 groups. CONCLUSIONS: Irradiation decreased MDR in NSCLC cells. In combination with a low-dose MDR modulator, GG918, MDR transport function was synergistically reduced 48 h post-irradiation.

Evaluation of an aspiration-type semiautomatic cutting biopsy needle.

PURPOSE: The purpose of this study was to evaluate an aspiration-type semiautomatic cutting biopsy needle for biopsy of bovine tissue. MATERIAL AND METHODS: Aspiration-type semiautomatic cutting biopsy needles (18 gauge × 160 mm) with aspiration (Group A), aspiration-type semiautomatic biopsy needles without aspiration (Group Wo), or normal-type semiautomatic biopsy needles (18 gauge × 150 mm) (Group N) were used in 10 biopsies each of bovine liver or lung. The specimens were weighed with an electronic balance. RESULTS: Mean (standard deviation) weights for bovine liver specimens in Groups A, Wo, and N were 6.80 (0.615) mg, 5.62 (0.843) mg, and 4.19 (0.140) mg, respectively. Mean weights of bovine lung specimens from Groups A, Wo, and N were 2.98 (0.828) mg, 2.67 (0.832) mg, and 1.94 (0.864) mg, respectively. A significant difference was seen between the 3 groups for bovine liver. However, a significant difference was only seen between Groups A and N for bovine lung. CONCLUSION: Bovine liver and lung specimens obtained using the aspiration-type semiautomatic cutting biopsy needle were heavier than those obtained using the normal-type semiautomatic biopsy needle.

Longitudinal time-dependent effects of irradiation on multidrug resistance in a non-small lung cancer cell line.

Multidrug resistance (MDR) in cancer is known to decrease the therapeutic efficacy of chemotherapy. The effects of irradiation on MDR in cancer cells remain unclear. Tc-99m methoxyisobutylisonitrile (MIBI) exhibits the same ATP-binding cassette (ABC) transporter kinetics as the chemotherapeutic compound doxorubicin. In this study, we investigated the synergistic effects of chemotherapeutics and irradiation [0 Gy: C (control) group; 3, 6, 9, 12 Gy: I (irradiation) group] in the human non-small lung cancer cell line H1299 exhibiting MDR, on MIBI and doxorubicin ABC transporter kinetics, in vitro and in vivo, respectively. In vitro, inhibition of H1299 cell proliferation by irradiation was found to be irradiation dose dependent. The degree and duration of MDR inhibition in vitro in H1299 were also dose dependent. In the cells of both the C group and 3-Gy I group, no significant difference of MIBI accumulation was observed. In the 6-Gy I group, a higher MIBI accumulation was observed at only 7 days after irradiation relative to the C group. A higher MIBI accumulation in the 9- and 12-Gy I groups with a significant difference from the C group was observed at 4 to 14 days after irradiation. A significant negative correlation between intracellular MIBI accumulation and cell replication was found. In vivo, high accumulation and retention of doxorubicin were observed in irradiated tumors in the H1299 xenograft mice group at 4 to 14 days after 9-Gy irradiation compared with the control mice group. These results provide evidence for a synergistic effect of concurrent chemotherapy and radiotherapy.