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Background and purpose Boron neutron capture therapy (BNCT) can be performed without reactors due to development of cyclotron-based epithermal neutron source (C-BENS), which is optimized for treatment for deeper-seated tumors. The purpose of this study was to evaluate efficacy and safety of cyclotron-based BNCT with borofalan (10B) for recurrent or locally advanced head and neck cancer. Materials and methods In this open-label, phase II JHN002 trial of BNCT using C-BENS with borofalan (10B), patients with recurrent squamous cell carcinoma (R-SCC) or with recurrent/locally advanced non-squamous cell carcinoma (R/LA-nSCC) of the head and neck were intravenously administered 400 mg/kg borofalan (10B), followed by neutron irradiation. The tumor dose was determined passively as the mucosal maximum dose of 12 Gy-Eq. The primary endpoint was the objective response rate (ORR). Post-trial observational JHN002 Look Up study was planned for evaluating locoregional progression-free survival (LRPFS). Results Eight R-SCC and 13 R/LA-nSCC patients were enrolled. All R-SCC patients had prior radiotherapy with a median dose of 65.5 Gy (range, 59.4–76.0 Gy). The ORR for all patients was 71%, and complete response/partial response were 50%/25% in R-SCC and 8%/62% in R/LA-nSCC. The 2-year overall survival for R-SCC and R/LA-nSCC were 58% and 100%, respectively. The median LRPFS was 11.5 months for R-SCC. Frequently observed adverse events included alopecia (95%), hyperamylasemia (86%), and nausea (81%). Conclusion These data suggest that BNCT using C-BENS with borofalan (10B) is a promising treatment option for patients with R-SCC or R/LA-nSCC of the head and neck.

BACKGROUND Boron neutron capture therapy (BNCT) is tumor-selective particle radiation and theoretically efficacious especially for tumors with infiltrative nature, such as glioblastoma (GBM). The aim of this study is to assess safety and efficacy of accelerator-based BNCT (AB-BNCT) using cyclotron-based neutron generator, BNCT30, and 10B-boronophenylalanine (borofalan(10B)) agent, SPM-011, in patients with recurrent malignant gliomas, chiefly GBM. METHODS The multi-institutional open-label, phase II clinical trial for recurrent 27 cases of malignant gliomas (MG) (24 cases were GBM) was conducted with above AB-BNCT system, using 500mg/kg of SPM-011 (study code, JG002). The patients were enrolled from February 2016 to June 2018. The inclusion criteria are bevacizumab-naïve MG, recurrent after standard treatment composed of XRT and chemotherapy with TMZ. Neutron-irradiation time were determined not to exceed to 8.5 Gy-Eq for scalp dose. Primary endpoint was 1-year survival rate and secondary ones were median overall survival (mOS), median progression free survival (mPFS). The results were compared to previous Japanese domestic bevacizumab trial for recurrent GBM (JO22506) which had the similar inclusion criteria with JG002. RESULTS 1-year survival rate and mOS of recurrent GBM cases in JG002 was 79.2% (95% CI:57.0–90.8) and 18.7 months (95% CI:12.9–23.4) respectively, while those of JO22506 was 34.5% (90% CI:20.0–49.0) and 10.5 months (95% CI:8.2–12.4), respectively. Median PFS of JG002 and JO22506 were 0.9 and 3.3 months, respectively. Most important adverse event in JG002 was brain edema. Brain edema in 21 out of 27 cases was treated with bevacizumab after progress disease. CONCLUSIONS AB-BNCT demonstrated acceptable safety and prolonged survival for recurrent MG chiefly GBM. AB-BNCT might produce brain edema somewhat after the treatment, which might be the unavoidable adverse event of re-irradiation for recurrent MG, however that seemed to be controlled well with bevacizumab.

The purpose of this study is to evaluate the dosimetric impact of the margin on the multileaf collimator-based dynamic tumor tracking plan. Furthermore, an equivalent setup margin (EM) of the tracking plan was determined according to the gated plan. A 4-dimensional extended cardiac-torso was used to create 9 digital phantom datasets of different tumor diameters (TDs) of 1, 3, and 5 cm and motion ranges (MRs) of 1, 2, and 3 cm. For each dataset, respiratory gating (30% to 70% phase) and tumor tracking treatment plans were prepared using 8-field 3-dimensional conformal radiation therapy by 4-dimensional dose calculation. The total lung V20 was calculated to evaluate the dosimetric impact for each case and to estimate the EM with the same impact on lung V20 obtained with the gating plan with a setup margin of 5 mm. The EMs for {TD = 1 cm, MR = 1 cm}, {TD = 1 cm, MR = 2 cm}, and {TD = 1 cm, MR = 3 cm} were estimated as 5.00, 4.16, and 4.24 mm, respectively. The EMs for {TD = 5 cm, MR = 1 cm}, {TD = 5 cm, MR = 2 cm}, and {TD = 5 cm, MR = 3 cm} were estimated as 4.24 mm, 6.35 mm, and 7.49 mm, respectively. This result showed that with a larger MR, the EM was found to be increased. In addition, with a larger TD, the EM became smaller. Our result showing the EMs provided the desired accuracy for multileaf collimator-based dynamic tumor tracking radiotherapy.

Hepatoblastoma is the most commonly occurring liver tumor in children. Preoperative chemotherapy and surgery have improved treatment outcomes; however, further improvements are required in the treatment of advanced cases. Recently, the efficacy of transarterial chemoembolization (TACE) has garnered attention. TACE increases the local concentration of drugs by transcatheterically administering antitumor agents, and induces necrosis in the tumor by embolizing the feeding artery. However, studies have revealed that tumors exhibit resistance to anticancer drugs in hypoxic environments. Metformin is a drug used to treat type 2 diabetes; however, recent reports have indicated that it may also exhibit antitumor effects in various cancer cell lines. These effects are hypothesized to be mediated by the activation of adenosine monophosphate-activated protein kinase and reduction of mammalian target of rapamycin signaling, but these effects occur at high concentrations that are not suitable for use in a clinical setting. The potential efficacy of metformin at increased physiological concentrations has not been evaluated. The present study investigated the therapeutic effect of low concentrations of metformin in combination with cisplatin on liver cancer HepG2 cells in hypoxic conditions. HepG2 cells were treated with cisplatin alone, metformin alone, or a combination of these two drugs and cultured in normoxia or hypoxia. Treatment with either 5 µM cisplatin or 1 mM metformin alone did not significantly affect cell proliferation or apoptosis in hypoxic conditions. However, when 5 µM cisplatin was combined with 1 mM metformin, a significant inhibition of cell proliferation and induction of apoptosis was observed in hypoxic HepG2 cells. In conclusion, a low concentration of metformin attenuates hypoxia-induced resistance to cisplatin in HepG2 cells. Selective delivery of an effective dose of metformin to a hepatoblastoma tumor may be achievable and clinically useful with TACE.

Background The efficacy, toxicity, and prognostic factors of high-dose proton beam therapy (PBT) for peripheral stage I non-small-cell lung cancer were assessed in this retrospective study. Materials and Methods Fifty patients with peripheral stage I non-small-cell lung cancer, two of whom had heterochronic multiple lung cancers, underwent high-dose PBT between January 2009 and September 2014. The relative biological effectiveness of the proton beam was defined as 1.1. The beam energy and spread-out Bragg peak were fine-tuned for the 90% isodose volume of the prescribed dosage to encompass the planning target volume. The cumulative survival curves were calculated using the Kaplan-Meier method. Treatment toxicities were evaluated using version 4 of the Common Terminology Criteria for Adverse Events, version 4. Results The study included 35 males and 15 females with a median age of 72.5 years. The median follow-up period was 22.8 months. The clinical stage was IA in 44 (85%) and IB in eight (15%) tumors. The total dose of PBT was 66 GyE in 10 fractions in all tumors. Three-year overall survival rate among all patients was 87.9% (95% confidence interval [CI], 94.8%-73.2%). Forty-five patients were alive, and 5 were dead. Three-year local control and progression-free survival rates were 95.7% (95% CI, 98.9%-83.8%) and 76.3% (95% CI, 86.9%-59.3%), respectively. Only one patient experienced Grade 2 pneumonitis. Conclusion High-dose PBT may be an effective and safe treatment option for patients with stage I non-small-cell lung cancer.

Purpose To evaluate, in Japan Clinical Oncology Group study 0403, the safety and efficacy of stereotactic body radiation therapy (SBRT) in patients with T1N0M0 non-small cell lung cancer (NSCLC). Methods and Materials Eligibility criteria included histologically or cytologically proven NSCLC, clinical T1N0M0. Prescribed dose was 48 Gy at the isocenter in 4 fractions. The primary endpoint was the percent (%) 3-year overall survival. The threshold % 3-year survival to be rejected was set at 35% for inoperable patients, whereas the expected % 3-year survival was 80% for operable patients. Results Between July 2004 and November 2008, 169 patients from 15 institutions were registered. One hundred inoperable and 64 operable patients (total 164) were eligible. Patients' characteristics were 122 male, 47 female; median age 78 years (range, 50-91 years); adenocarcinomas, 90; squamous cell carcinomas, 61; others, 18. Of the 100 inoperable patients, the % 3-year OS was 59.9% (95% confidence interval 49.6%-68.8%). Grade 3 and 4 toxicities were observed in 10 and 2 patients, respectively. No grade 5 toxicity was observed. Of the 64 operable patients, the % 3-year OS was 76.5% (95% confidence interval 64.0%-85.1%). Grade 3 toxicities were observed in 5 patients. No grade 4 and 5 toxicities were observed. Conclusions Stereotactic body radiation therapy for stage I NSCLC is effective, with low incidences of severe toxicity. This treatment can be considered a standard treatment for inoperable stage I NSCLC. This treatment is promising as an alternative to surgery for operable stage I NSCLC.

2536 Background: Boron neutron capture therapy (BNCT) is tumor-selective particle radiation and theoretically efficacious especially for tumors with infiltrative nature, such as glioblastoma (GBM). The aim of this study is to assess safety and efficacy of accelerator-based BNCT (AB-BNCT) using cyclotron-based neutron generator, BNCT30, and 10B-boronophenylalanine (borofalan(10B)) agent, SPM-011, in patients with recurrent malignant gliomas, chiefly GBM. Methods: The multi-institutional open-label, phase II clinical trial for recurrent 27 cases of malignant gliomas (MG) (24 cases were GBM) was conducted with above mentioned AB-BNCT system, using 500mg/kg of SPM-011 (study code, JG002). The patients were enrolled from February 2016 to June 2018. The inclusion criteria are bevacizumab-naïve MG, recurrent after standard treatment composed of XRT and chemotherapy with TMZ. Neutron-irradiation time were determined not to exceed to 8.5 Gy-Eq for scalp dose which was decided by preceding phase I trial. Primary endpoint was 1-year survival rate and secondary ones were median overall survival (mOS), median progression free survival (mPFS) and so on. The results were compared to previous Japanese domestic bevacizumab trial for recurrent GBM (JO22506) which had the similar inclusion criteria with JG002. Results: 1-year survival rate and mOS of recurrent GBM cases in JG002 was 79.2% (95% CI:57.0-90.8) and 18.7 months (95% CI:12.9-23.4) (data cutoff = 20 Jun 2019) respectively, while those of JO22506 was 34.5% (90% CI:20.0-49.0) and 10.5 months (95% CI:8.2-12.4), respectively. Median PFS of JG002 and JO22506 were 0.9 and 3.3 months, respectively. Most important adverse event in JG002 was brain edema. 21 out of 27 cases were treated with bevacizumab after progress disease. Conclusions: AB-BNCT demonstrated acceptable safety and prolonged survival for recurrent MG chiefly GBM. AB-BNCT might produce brain edema somewhat after the treatment, which might be the unavoidable adverse event of re-irradiation for recurrent MG, however that seemed to be controlled with bevacizumab. Clinical trial information: JapicCTI-194742 . [Table: see text]

Background The purpose of this study was to evaluate the impact of markerless on-board kilovoltage (kV) cone-beam computed tomography (CBCT)-based positioning uncertainty on determination of the planning target volume (PTV) margin by comparison with kV on-board imaging (OBI) with gold fiducial markers (FMs), and to validate a methodology for the evaluation of PTV margins for markerless kV-CBCT in prostate image-guided radiotherapy (IGRT). Methods A total of 1177 pre- and 1177 post-treatment kV-OBI and 1177 pre- and 206 post-treatment kV-CBCT images were analyzed in 25 patients who received prostate IGRT with daily localization by implanted FMs. Intrafractional motion of the prostate was evaluated between each pre- and post-treatment image with these two different techniques. The differences in prostate deviations and intrafractional motions between matching by FM in kV-OBI (OBI-FM) and matching by soft tissues in kV-CBCT (CBCT-ST) were compared by Bland-Altman limits of agreement. Compensated PTV margins were determined and compensated by references. Results Mean differences between OBI-FM and CBCT-ST in the anterior to posterior (AP), superior to inferior (SI), and left to right (LR) directions were − 0.43 ± 1.45, − 0.09 ± 1.65, and − 0.12 ± 0.80 mm, respectively, with R2 = 0.85, 0.88, and 0.83, respectively. Intrafractional motions obtained from CBCT-ST were 0.00 ± 1.46, 0.02 ± 1.49, and 0.15 ± 0.64 mm, respectively, which were smaller than the results from OBI-FM, with 0.43 ± 1.90, 0.12 ± 1.98, and 0.26 ± 0.80 mm, respectively, with R2 = 0.42, 0.33, and 0.16, respectively. Bland-Altman analysis showed a significant proportional bias. PTV margins of 1.5 mm, 1.4 mm, and 0.9 mm for CBCT-ST were calculated from the values of CBCT-ST, which were also smaller than the values of 3.15 mm, 3.66 mm, and 1.60 mm from OBI-FM. The practical PTV margin for CBCT-ST was compensated with the values from OBI-FM as 4.1 mm, 4.8 mm, and 2.2 mm. Conclusions PTV margins calculated from CBCT-ST might be underestimated compared to the true PTV margins. To determine a reliable CBCT-ST-based PTV margin, at least the systemic error Σ and the random error σ for on-line matching errors need to be investigated by supportive preliminary FM evaluation at least once.

Background The purpose of this study was to investigate the differences in the dosimetric advantage of using intraoperatively built custom-linked (IBCL) seeds between permanent iodine-125 (I-125) seed implantation (PI) alone and PI followed by external-beam radiation therapy (EBRT) for prostate cancer. Methods We reviewed the records of 62 patients with localized prostate cancer who received transperineal interstitial brachytherapy with I-125 using free seeds or IBCL seeds. Twenty-four low- and intermediate-risk patients underwent PI alone with the prescribed dose of 160 Gy, and 39 high-risk patients underwent PI with 110 Gy, followed by EBRT with 45 Gy (PI + EBRT). Intraoperative and post-implant dosimetric parameters 1 month after implantation were collected and analyzed. Results The numbers of patients implanted with free seeds and IBCL seeds were 14 (58.3%) and 10 (41.7%), respectively, in the PI group and 25 (65.8%) and 13 (34.2%), respectively, in the PI + EBRT group. In the PI group, although there were significant differences in prostate V100 (p = 0.003) and D90 (p = 0.009) and rectum V100 (p = 0.026) on intraoperative dosimetry, these differences were not found on post-implant dosimetry. In the PI + EBRT group, the dosimetric parameters of IBCL seeds, such as prostate V200 (p = 0.013) and V250 (p = 0.010) and urethra D30 (p = 0.038), were better than those of free seeds on intraoperative dosimetry. Furthermore, even on post-implant dosimetry, prostate D90 (p = 0.004), V150 (p = 0.001), and homogeneity index (HI, p = 0.001), as well as V200 (p = 0.001) and V250 (p = 0.020), and urethra D5 (p = 0.008) as well as D30 (p = 0.003) had a better dosimetric quality in IBCL seeds than in free seeds. There was no significant difference in the operation time between free seeds and IBCL seeds in each PI and PI + EBRT group. Conclusions Our results reveal that greater dosimetric benefits could be obtained using IBCL seeds in the case of permanent implantation with a lower prescribed dose, such as PI + EBRT, rather than PI alone.

The purpose of this study was to investigate clinical outcomes following stereotactic body radiotherapy (SBRT) for lung metastases as oligo-recurrence. From May 2003 to June 2014, records for 66 patients with 76 oligo-recurrences in the lungs treated with SBRT were retrospectively reviewed. Oligo-recurrence primary sites and patient numbers were as follows: lungs, 31; colorectal, 13; head and neck, 10; esophagus, 3; uterus, 3; and others, 6. The median SBRT dose was 50 Gy (range, 45–60 Gy) administered in a median of 5 (range, 5–9) fractions. All patients received SBRT, with no acute toxicity. Surviving patients had a median follow-up time of 36.5 months. The 3-year rates of local control, overall survival and disease-free survival were 90.6%, 76.0% and 53.7%, respectively. Longer disease-free interval from initial treatment to SBRT, and non-colorectal cancer were both associated with favorable outcomes. Disease progression after SBRT occurred in 31 patients, most with distant metastases (n = 24) [among whom, 87.5% (n = 21) had new lung metastases]. Among these 21 patients, 12 were judged as having a second oligo-recurrence. Additional SBRT was performed for these 12 patients, and all 12 tumors were controlled without disease progression. Three patients (4.5%) developed Grade 2 radiation pneumonitis. No other late adverse events of Grade ≥2 were identified. Thus, SBRT for oligo-recurrence achieved acceptable tumor control, with additional SBRT also effective for selected patients with a second oligo-recurrence after primary SBRT.

Radioactive iodine (131I) therapy in patients suffering from differentiated thyroid cancer (DTC) is a targeted treatment commonly used for thyroid ablation and locoregional and distant metastatic spread management. Despite a significant proportion of the 131I dose entering the circulation, there is currently no detailed information regarding its effect on the blood cell system. In order to assess the cytotoxic effects of 131I therapy on the circulatory system, blood cell levels, thyroid-related hormones and CD45+ cell cytotoxicity were estimated in blood collected from patients with DTC. The micronuclei (MN) frequency of the peripheral blood CD45+ cell fraction was significantly increased after 30 days of 131I therapy compared to that prior to treatment, although a strong individual variation was observed. A significantly negative correlation between MN frequency and the level of platelets and plateletcrit was observed; however, there was no such correlation with thyroid-related hormones. These resultS suggest that the correlation between MN frequency and the platelet system may serve as a biomarker of exposure and, possibly, of sensitivity in DTC patients undergoing 131I therapy following thyroid and lymph node surgery.

The purpose of this study was to investigate the relationship between tumor size and blood volume for patients with lung tumors, using dual-energy computed tomography (DECT) and a gemstone spectral imaging (GSI) viewer. During the period from March 2011 to March 2013, 50 patients with 57 medically inoperable lung tumors underwent DECT before stereotactic body radiotherapy (SBRT) of 50-60 Gy in 5-6 fractions. DECT was taken for pretreatment evaluation. The region-of-interest for a given spatial placement of the tumors was set, and averages for CT value, water density and iodine density were compared with tumor size. The average values for iodine density in tumors of ≤ 2 cm, 2-3 cm, and >3 cm maximum diameter were 24.7, 19.6 and 16.0 (100 µg/cm(3)), respectively. The average value of the iodine density was significantly lower in larger tumors. No significant correlation was detected between tumor size and average CT value or between tumor size and average water density. Both the average water density and the average CT value were affected by the amount of air in the tumor, but the average iodine density was not affected by air in the tumor. The average water density and the average CT value were significantly correlated, but the average iodine density and the average CT value showed no significant correlation. The blood volume of tumors can be indicated by the average iodine density more accurately than it can by the average CT value. The average iodine density as assessed by DECT might be a non-invasive and quantitative assessment of the radio-resistance ascribable to the hypoxic cell population in a tumor.

Incidental 18F-fluorodeoxyglucose (18F-FDG) uptake in the prostate is often experienced in clinical practice; however, it is difficult to determine whether incidental uptake is indicative of a malignancy or benign state based on the maximum standardized uptake value (SUVmax). In the present study, we investigated the clinical significance of incidental prostate uptake by 18F-FDG positron emission tomography (PET)/CT, and examined the differences between malignant and benign uptake from a clinicopathological viewpoint. We reviewed 3,236 male subjects who underwent 18F-FDG PET/CT scans at Hirosaki University Hospital (Japan) from 2008 to 2012 in order to identify cases of incidental prostate FDG uptake. The final diagnosis was made by serum prostate-specific antigen (PSA) levels, biopsy, imaging studies and clinical follow-up with PET findings. Incidental FDG uptake of the prostate was observed in 53 cases (2%). Four cases were excluded due to insufficient clinical data, and 49 cases were included in the present study. Of the 49 cases, 8 (16%) had prostate cancer, while 41 (84%) were benign. All 8 malignant cases had high uptake areas, e.g. in the prostate peripheral zone, where there was no coexistence of calcification or FDG uptake. Of the 41 benign cases, 19 had high uptake in the inner zone, 17 in the peripheral zone, and 5 in both the inner and peripheral zones. Of the 41 cases, 18 (44%) showed FDG uptake coexisting with prostatic calcification. Incidental prostate 18F-FDG uptake infrequently signifies prostate cancer; however, FDG uptake not coexisting with calcification indicates the possibility of prostate cancer and should be included in the differential diagnosis for performing other clinical examinations.

6028 Background: To assess safety and efficacy of accelerator-based boron neutron capture therapy (AB-BNCT) using cyclotron-based neutron generator, BNCT30, and 10B-boronophenylalanine (borofalan(10B)) agent, SPM-011, in patients with recurrent squamous cell carcinoma (R-HNSCC) or recurrent/locally advanced non-squamous cell carcinoma (R/LA-HNNSCC) of the head and neck. Methods: The multi-institutional open-label, a world-first phase II trial of AB-BNCT in patients with inoperable R-HNSCC which present resistance to platinum-based chemotherapy, or with inoperable R/LA-HNNSCC, was conducted to assess safety and antitumor activity of AB-BNCT with BNCT30 and SPM-011. SPM-011 was administered at 200 mg/kg/h intravenously for 2 hours, followed by neutron irradiation with continuous infusion of SPM-011 at 100 mg/kg/h. The irradiated dose for tumor was determined passively as a mucosal maximum dose was given 12 Gy-Eq in calculation with a blood boron concentration measured just before the start of neutron irradiation. Primary endpoint was objective response rate (ORR) by central review. Tumor response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) ver 1.1 every 4 weeks for the first 3 months and every 12 weeks thereafter. Results: Eight R-HNSCC and thirteen R/LA-HNNSCC patients were enrolled and received AB-BNCT. All R-HNSCC patients had prior radiotherapy with a median dose of 65.5 Gy (range 59.4–76.0). The median irradiation time was 43 min (range 26–65). The median tumor minimum dose was 31.0 Gy-Eq (range 16.1–42.6). For adverse event, nausea (81%), dysgeusia (71%), parotitis (67%) were observed more frequently. The ORR for all patients were 71.4%, and CR/PR were 50.0%/25.0% in R-HNSCC and 7.7%/61.5% in R/LA-HNNSCC. At a median follow up of 18.8 months (range 9.2–29.0), 1-year PFS and OS by investigator assessment were 70.6% and 100%, respectively. The data for antitumor activity is still immature and will be further updated. Conclusions: AB-BNCT for R-HNSCC and R/LA-HNNSCC demonstrated an acceptable safety profile and a promising antitumor activity.

The nasal type of extranodal natural killer (NK)/T-cell lymphoma (NKTCL) is a rare aggressive lymphoma with poor prognosis. The reported 5-year overall survival for patients with localized nasal NKTCL treated with cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone (CHOP) is

Purpose Radioresistance is a major cause of treatment failure of radiotherapy (RT) in human cancer. We have recently revealed that acquired radioresistance of tumor cells induced by fractionated radiation is attributable to cyclin D1 overexpression as a consequence of the downregulation of GSK3β-dependent cyclin D1 proteolysis mediated by a constitutively activated serine-threonine kinase, AKT. This prompted us to hypothesize that targeting the AKT/GSK3β/cyclin D1 pathway may improve fractionated RT by suppressing acquired radioresistance of tumor cells. Methods and Materials Two human tumor cell lines with acquired radioresistance were exposed to X-rays after incubation with either an AKT inhibitor, AKT/PKB signaling inhibitor-2 (API-2), or a Cdk4 inhibitor (Cdk4-I). Cells were then subjected to immunoblotting, clonogenic survival assay, cell growth analysis, and cell death analysis with TUNEL and annexin V staining. In vivo radiosensitivity was assessed by growth of human tumors xenografted into nude mice. Results Treatment with API-2 resulted in downregulation of cyclin D1 expression in cells with acquired radioresistance. Cellular radioresistance disappeared completely both in vitro and in vivo with accompanying apoptosis when treated with API-2. Furthermore, inhibition of cyclin D1/Cdk4 by Cdk4-I was sufficient for abolishing radioresistance. Treatment with either API-2 or Cdk4-I was also effective in suppressing resistance to cis-platinum (II)-diamine-dichloride in the cells with acquired radioresistance. Interestingly, the radiosensitizing effect of API-2 was canceled by overexpression of cyclin D1 whereas Cdk4-I was still able to sensitize cells with cyclin D1 overexpression. Conclusion Cyclin D1/Cdk4 is a critical target of the AKT survival signaling pathway responsible for tumor radioresistance. Targeting the AKT/GSK3β/cyclin D1/Cdk4 pathway would provide a novel approach to improve fractionated RT and would have an impact on tumor eradication in combination with chemotherapy.

頭頸部癌の動注併用放射線療法における動注血管選択度の違いによる治療効果と，動注手技由来合併症を検討した。対象は動注化学療法を施行した頭頸部癌93症例，全247回の動注手技。病期はIV期が過半数。動注手技により超選択的動注群67例と非選択的動注群（金属コイルでの血流改変を併用）26例に分類。このうち根治照射を併用した粘膜扁平上皮癌初回治療例（56例）で一次治療効果を検討したところ，原発巣の治療効果は超選択的動注群42例中CR 27例（64.3%），PR 15例（35.7%），非選択的動注群14例中CR 10例（71.4%），PR 4例（28.6%）で，両群間に有意差はなかった。動注手技由来合併症は全93例で検討したが，超選択的動注群で67例中4例（6.0%），非選択的動注群で26例中1例（3.8%）に生じており両群間に有意差はなかった。放射線療法併用のもと，非選択的動注療法は超選択的動注法と同等に有効な動注法である。

OBJECTIVES: The objectives of this study were to reveal the utility of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) within 7 days after chemoradiotherapy to predict prognosis in patients with postoperative recurrent esophageal cancer. MATERIALS AND METHODS: Patients scheduled to undergo concurrent chemoradiotherapy for postoperative locoregional recurrence of esophageal cancer were recruited. Selection criteria were: (1) locoregional recurrence, (2) no previous radiation therapy, (3) planning treatment with concurrent chemoradiotherapy, (4) FDG-PET performed

To investigate the relationships of plasma levels of brain natriuretic peptide (BNP) with abnormal (18)F-fluorodeoxyglucose (FDG) accumulation in the myocardium corresponding to irradiated fields and temporal changes in BNP, which is used as an index of heart remodeling, after radiotherapy for the mediastinum.Brain natriuretic peptide concentrations were measured before and after radiotherapy for thoracic esophageal cancer, and the change in BNP concentration after radiotherapy was investigated. Moreover, FDG accumulation in the myocardium was investigated in patients who had undergone FDG positron emission tomography less than 14 days before or after measurement of BNP concentration, and the Mann-Whitney U test was used to detect significant difference between BNP concentrations in patients with and without abnormal FDG accumulation corresponding to the irradiated field.There was significant difference between the levels of BNP in patients without abnormal FDG accumulation in the irradiated myocardium and in patients with abnormal FDG accumulation (p0.001). The levels of BNP in the 9-24 months after radiotherapy group and in the24 months after radiotherapy group were significantly higher than the levels in the before radiotherapy group, immediately after radiotherapy group, 1-2 months after radiotherapy group, and control group.The level of BNP was significantly increased more than 9 months after the start of radiotherapy and was significantly higher in patients who had high FDG accumulation corresponding to the irradiated field. The results of this study indicate that BNP concentration might be an early indicator of radiation-induced myocardial damage.

Introduction: Hypofractionated stereotactic radiotherapy (HypoFXSRT) has recently been used for the treatment of small lung tumors. We retrospectively analyzed the treatment outcome of HypoFXSRT for stage I non-small cell lung cancer (NSCLC) treated in a Japanese multi-institutional study. Methods: This is a retrospective study to review 257 patients with stage I NSCLC (median age, 74 years: 164 T1N0M0, 93 T2N0M0) were treated with HypoFXSRT alone at 14 institutions. Stereotactic three-dimensional treatment was performed using noncoplanar dynamic arcs or multiple static ports. A total dose of 18 to 75 Gy at the isocenter was administered in one to 22 fractions. The median calculated biological effective dose (BED) was 111 Gy (range, 57–180 Gy) based on / 10. Results: During follow-up (median, 38 months), pulmonary complications of above grade 2 arose in 14 patients (5.4%). Local progression occurred in 36 patients (14.0%), and the local recurrence rate was 8.4% for a BED of 100 Gy or more compared with 42.9% for less than 100 Gy (p 0.001). The 5-year overall survival rate of medically operable patients was 70.8% among those treated with a BED of 100 Gy or more compared with 30.2% among those treated with less than 100 Gy (p 0.05). Conclusions: Although this is a retrospective study, HypoFXSRT with a BED of less than 180 Gy was almost safe for stage I NSCLC, and the local control and overall survival rates in 5 years with a BED of 100 Gy or more were superior to the reported results for conventional radiotherapy. For all treatment methods and schedules, the local control and survival rates were better with a BED of 100 Gy or more compared with less than 100 Gy. HypoFXSRT is feasible for curative treatment of patients with stage I NSCLC.

Background Radiation-induced rib fracture after stereotactic body radiotherapy (SBRT) for lung cancer has been recently reported. However, incidence of radiation-induced rib fracture after SBRT using moderate fraction sizes with a long-term follow-up time are not clarified. We examined incidence and risk factors of radiation-induced rib fracture after SBRT using moderate fraction sizes for the patients with peripherally located lung tumor. Methods During 2003–2008, 41 patients with 42 lung tumors were treated with SBRT to 54–56 Gy in 9–7 fractions. The endpoint in the study was radiation-induced rib fracture detected by CT scan after the treatment. All ribs where the irradiated doses were more than 80% of prescribed dose were selected and contoured to build the dose-volume histograms (DVHs). Comparisons of the several factors obtained from the DVHs and the probabilities of rib fracture calculated by Kaplan-Meier method were performed in the study. Results Median follow-up time was 68 months. Among 75 contoured ribs, 23 rib fractures were observed in 34% of the patients during 16–48 months after SBRT, however, no patients complained of chest wall pain. The 4-year probabilities of rib fracture for maximum dose of ribs (Dmax) more than and less than 54 Gy were 47.7% and 12.9% (p = 0.0184), and for fraction size of 6, 7 and 8 Gy were 19.5%, 31.2% and 55.7% (p = 0.0458), respectively. Other factors, such as D2cc, mean dose of ribs, V10–55, age, sex, and planning target volume were not significantly different. Conclusions The doses and fractionations used in this study resulted in no clinically significant rib fractures for this population, but that higher Dmax and dose per fraction treatments resulted in an increase in asymptomatic grade 1 rib fractures.

Purpose: Nitroglycerin may improve the response to chemotherapy in advanced non–small cell lung cancer. The effects and mechanisms of nitroglycerin on the enhancement of chemosensitivity to docetaxel and carboplatin regimen (DCb) in patients with lung adenocarcinoma have not been reported.Experimental Design: Seventeen patients with operable lung adenocarcinoma and stable angina pectoris were selected to investigate the effects of nitroglycerin on immunoreactivity for hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), P-glycoprotein (P-gp), the production of which is regulated by HIF-1, and p53 proteins in their resected tumor by semiquantitative immunohistochemical analyses. Eight of 17 patients were treated with nitroglycerin patches before operation, but 9 of 17 patients were not. Furthermore, to study the relationship between changes in plasma VEGF levels by nitroglycerin treatment and response to DCb, 29 patients with advanced lung adenocarcinoma were treated with nitroglycerin for 3 days before chemotherapy using DCb.Results: The rates of immunoreactive cells for HIF-1α, VEGF, and P-gp in tumor tissues treated with nitroglycerin were lower than those without nitroglycerin, but those for p53 were not different between those treated with and without nitroglycerin. Furthermore, the rates of immunoreactive cells for VEGF and P-gp proteins were significantly associated with those for HIF-1α in tumor tissue. The magnitude of decrease in plasma VEGF levels after treatment with nitroglycerin was significantly associated with response to DCb in patients with advanced lung adenocarcinoma.Conclusions: Nitroglycerin treatment may improve response to DCb in patients with lung adenocarcinoma, partly through decreasing VEGF and P-gp production via reduction of HIF-1α.

Purpose: We evaluated the clinical significance of focal increased uptake in the basal myocardium on F-fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with esophageal cancer after radiotherapy. Methods and Materials: Between August 2004 and July 2005, a total of 64 patients who had been irradiated for thoracic esophageal cancer underwent FDG-PET at least three months after the completion of chemoradiotherapy. Some patients showed increased FDG uptake in the basal portion of the myocardium. To clarify the clinical significance of these findings, further examinations of hearts were performed. The dose distribution in the myocardium with high FDG uptake was also analyzed retrospectively. Results: Thirteen (20.3%) of the 64 patients showed high FDG uptake in the basal myocardium corresponding to the irradiated fields compared with FDG uptake in the myocardium outside the irradiated fields. Eight of the 13 patients consented to undergo examinations of the heart. Five of those eight patients showed low 123 I-BMIPP uptake and four showed low 201 TlCl uptake in the myocardium corresponding with high FDG uptake regions. In two patients, delayed enhancement was found in some parts of the area with high FDG uptake on Gd-DTPA magnetic resonance imaging (MRI), and the delay-enhanced lesion showed hypokinesia on cine-MRI in one patient. Conclusions: FDG-PET often shows focal increased uptake in the basal myocardium after radiotherapy for esophageal cancer. This finding indicates the possibility of radiation-induced cardiac damage, and cardiac function and symptoms of such patients should be followed carefully.

OBJECTIVE: No previous studies have reported the longitudinal health-related quality of life (HRQOL) for intensity modulated radiation therapy (IMRT). We compared HRQOL after IMRT with that after conventional and after conformal radiation therapy (XRT). METHODS: A total of 110 patients underwent XRT (34 patients underwent conventional radiation therapy and 76 underwent conformal radiation therapy) and 30 underwent IMRT for clinically localized prostate cancer between 2000 and 2002. We measured the general and disease-specific HRQOL using the Medical Outcomes Study 36-Item Health Survey and University of California, Los Angeles, Prostate Cancer Index, respectively. RESULTS: There were no significant differences in the preoperative characteristics and HRQOL scores of the two groups. Repeated measure analyses of variance revealed significantly different patterns of alteration in several general HRQOL domains between XRT and the IMRT groups. In the urinary domain, there was no difference in the alteration patterns between the two groups. The XRT group suffered worse bowel function at 3 and 6 months than the IMRT group (P < 0.05). In the XRT group, sexual function decreased at 3 months and remained substantially lower than the baseline level. However, the IMRT group showed no significant difference from the baseline level at any of the observation periods. At 18 months the XRT group showed worse sexual function than the IMRT group. CONCLUSION: The two approaches showed different longitudinal profiles regarding general and disease-specific HRQOL during the first 2 years after treatment. The IMRT approach produced little impairment in bowel and sexual function.

The aim of this study was to investigate the prognostic role of the pretreatment neutrophil-to-lymphocyte ratio (NLR) as a predictive marker prior to treatment of cervical cancer with radiation therapy (RT) alone or concurrent chemoradiation therapy (CCRT).Fifty-six patients with squamous cell carcinoma (SCC) of the uterine cervix who underwent RT or CCRT from 2005-2013 at the Hirosaki University Hospital were retrospectively identified using electronic databases. Patients were divided into a high NLR group (≥2.5) and a low NLR group (2.5). The efficacy of RT and CCRT in the two groups was compared.Of the 56 patients, 35 were in the high NLR group and 21 were in the low NLR group. In comparison to a high NLR, a low NLR was significantly associated with a complete response (P0.001). When cancer was divided into stages I/II and III/IV, patients with a low NLR had a significantly better therapeutic outcome than those with a high NLR (P0.05). Multivariate analysis showed that only the NLR was a significant prognostic factor for progression-free survival (PFS) and overall survival (OS). Patients with a high NLR had significantly shorter PFS and OS than those with a low NLR.Results showed that a low NLR before treatment could predict a good response to RT or CCRT at all stages of uterine cervical cancer. The NLR may be a promising parameter on which to base the choice of a therapeutic strategy to treat SCC of the uterine cervix.

Purpose: To analyze the outcomes of radiation therapy for patients with residual superficial esophageal cancer (rSEC) after endoscopic mucosal resection (EMR). Methods and Materials: From May 1996 to October 2002, a total of 30 rSEC patients without lymph node metastasis received radiation therapy at Tohoku University Hospital and associated hospitals. The time interval from EMR to start of radiation therapy ranged from 9 to 73 days (median interval, 40 days). Radiation doses ranged from 60 Gy to 70 Gy (mean dose, 66 Gy). Chemotherapy was used in 9 of 30 patients (30%). Results: The 2-year, 3-year, and 5-year overall survival rates and cause-specific survival rates were 91%, 82%, and 51%, respectively, and 95%, 85%, and 73%, respectively. The 2-year, 3-year, and 5-year local control rates for mucosal cancer were 91%, 91%, and 91%, respectively, and those for submucosal cancer were 89%, 89%, and 47%, respectively. These differences in survival rates for patients with two types of cancer were not statistically significant. Local recurrence and lymph node recurrence were more frequent in patients with submucosal cancer than in patients with mucosal cancer ( p = 0.38 and p = 0.08, respectively). Esophageal stenosis that required balloon dilatation developed in 3 of the 30 patients, and radiation pneumonitis that required steroid therapy developed in 1 patient. Conclusions: Radiation therapy is useful for preventing local recurrence after incomplete EMR.

Purpose: To evaluate the factors associated with acute esophagitis in lung cancer patients treated with thoracic radiotherapy. Methods and Materials: We examined 35 patients with non-small-cell lung cancer ( n = 27, 77%) and small-cell lung cancer ( n = 8, 23%) treated with thoracic radiotherapy between February 2003 and November 2004. The median patient age was 70 years (range, 50–83 years). The disease stage was Stage I in 2 patients (6%), Stage II in 1 (3%), Stage IIIa in 10 (28%), Stage IIIb in 9 (26%), and Stage IV in 9 (26%); 4 patients (11%) had recurrent disease after surgery. A median dose of 60 Gy (range, 50–67 Gy) was given to the isocenter and delivered in single daily fractions of 1.8 or 2 Gy. With heterogeneity corrections, the median given dose to the isocenter was 60.3 Gy (range, 49.9–67.2 Gy). Of the 35 patients, 30 (86%) received concurrent chemotherapy consisting of a platinum agent, cisplatin or carboplatin, combined with paclitaxel in 18 patients (52%), irinotecan hydrochloride in 7 (20%), vincristine sulfate and etoposide in 2 (5%), vinorelbine ditartrate in 1 (3%), etoposide in 1 (3%), and docetaxel in 1 patient (3%). Three of these patients underwent induction therapy with cisplatin and irinotecan hydrochloride, administered before thoracic radiotherapy, and concurrent chemotherapy. Esophageal toxicity was graded according to the Radiation Therapy Oncology Group criteria. The following factors were analyzed with respect to their association with Grade 1 or worse esophagitis by univariate and multivariate analyses: age, gender, concurrent chemotherapy, chemotherapeutic agents, maximal esophageal dose, mean esophageal dose, and percentage of esophageal volume receiving >10 to >65 Gy in 5-Gy increments. Results: Of the 35 patients, 25 (71%) developed acute esophagitis, with Grade 1 in 20 (57%) and Grade 2 in 5 (14%). None of the patients had Grade 3 or worse toxicity. The most significant correlation was between esophagitis and percentage of esophageal volume receiving >35 Gy on univariate ( p = 0.002) and multivariate ( p = 0.018) analyses. Conclusion: The percentage of esophageal volume receiving >35 Gy was the most statistically significant factor associated with mild acute esophagitis.

Purpose The prognosis and the radiosensitivity of macroscopically infiltrative type of esophageal carcinoma are worse than those of the localized type of esophageal carcinoma treated with irradiation. The aim of this study was to investigate the cause of differences in radiosensitivity and prognosis of esophageal carcinoma according to macroscopic type from the viewpoint of tumor angiogenesis. Methods and materials A total of 40 surgically resected esophageal carcinoma tissues with good material remaining were selected at random from macroscopically localized type ( n = 20) and infiltrative type ( n = 20) of esophageal carcinoma. The highest intratumoral microvascular density (h-MVD), average intratumoral microvascular density (a-MVD), Ki67 labeling index, and expression of vascular endothelial growth factor (VEGF) in each section were estimated. Results h-MVD was significantly ( p = 0.0006) greater in the infiltrative type than in the localized type, whereas a-MVD ( p = 0.0014) and Ki67 labeling index ( p = 0.022) were significantly lower in the infiltrative type than in the localized type. The expression level of VEGF was significantly ( p Conclusions The generally underdeveloped vascular densities with low proliferation activities (suggesting increase of hypoxic fraction) seemed to be one of the reasons for unfavorable radiosensitivities of infiltrative type of esophageal carcinoma. The infiltrative type of esophageal carcinoma shows a high level of VEGF expression and high activity of tumor angiogenesis. The locally enhanced neovascularization, which occurs frequently in hematogenous metastasis seemed to be one of the reasons for the unfavorable prognosis of the infiltrative type of esophageal carcinoma.

BACKGROUND Stereotactic irradiation (STI) has been actively performed using various methods to achieve better local control of Stage I nonsmall cell lung carcinoma (NSCLC) in Japan. The authors retrospectively evaluated results from a Japanese multiinstitutional study. METHODS Patients with Stage I NSCLC (n = 245; median age, 76 years; T1N0M0, n=155; T2N0M0, n=90) were treated with hypofractionated high-dose STI in 13 institutions. Stereotactic three-dimensional treatment was performed using noncoplanar dynamic arcs or multiple static ports. A total dose of 18–75 gray (Gy) at the isocenter was administered in 1–22 fractions. The median calculated biologic effective dose (BED) was 108 Gy (range, 57–180 Gy). RESULTS During follow-up (median, 24 months; range, 7–78 months), pulmonary complications of National Cancer Institute-Common Toxicity Criteria Grade > 2 were observed in only 6 patients (2.4%). Local progression occurred in 33 patients (14.5%), and the local recurrence rate was 8.1% for BED ≥ 100 Gy compared with 26.4% for < 100 Gy (P < 0.05). The 3-year overall survival rate of medically operable patients was 88.4% for BED ≥ 100 Gy compared with 69.4% for < 100 Gy (P < 0.05). CONCLUSIONS Hypofractionated high-dose STI with BED < 150 Gy was feasible and beneficial for curative treatment of patients with Stage I NSCLC. For all treatment methods and schedules, local control and survival rates were better with BED ≥ 100 Gy compared with < 100 Gy. Survival rates in selected patients (medically operable, BED ≥ 100 Gy) were excellent, and were potentially comparable to those of surgery. Cancer 2004. © 2004 American Cancer Society.

From January 1999 to November 2000, a total of 24 esophageal cancer patients (17 untreated and 7 recurrent cases) were treated with radiation therapy (60-70 Gy) combined with cis-diammine-glycolatoplatinum (Nedaplatin) (80-120 mg/body) and 5-fluorouracil (5-FU) (500-1,000 mg/body/24 h, continuous infusion for 5 days). Grade III leukocytopenia was observed in 6 (25%) of the patients. Grade III and IV thrombocytopenia was observed in one patient each. The 1-year and 2-year survival rates for definitively irradiated patients were 59% and 39%, respectively, and for patients with postoperative recurrence 69% and 69%, respectively. High-dose radiation combined with Nedaplatin and 5-FU is a safe and effective method for treating esophageal cancer.

Several studies have noted benign thecoma‑fibroma tumors with positive F‑18 fluorodeoxyglucose (FDG) accumulation mimicking malignant ovarian tumors following F‑18 FDG positron emission tomography (PET). The present study analyzed four cases with false‑positive F‑18 FDG PET/computed tomography (CT) diagnoses of thecoma‑fibroma tumors as malignant tumors due to F‑18 FDG accumulation, compared with eight cases of FDG‑positive ovarian cancers and two cases of FDG‑negative fibromas. Hypoxia inducible factor (HIF)‑1α expression was examined in the six thecoma‑fibroma tumors using reverse transcription‑polymerase chain reaction (RT‑PCR). The four F‑18 FDG‑positive cases exhibited higher cellularity, maximum standard uptake and signal intensity on T2‑weighted imaging, and gadolinium (Gd) enhancement using magnetic resonance imaging than the two FDG-negative fibroma cases. In the F‑18 FDG‑positive thecoma‑fibroma group, Ki‑67 expression was low and LAT1 expression was not identified, ruling out the diagnosis and potential for malignancy. However, considerable glucose transporter 1, HIF‑1α, and vascular endothelial growth factor expression was observed. HIF‑1α expression was elevated in all four false‑positive cases by RT‑PCR. From these results, it was hypothesized that hypoxia due to elevated cellularity may stimulate HIF‑1α expression and be associated with F‑18 FDG accumulation in F‑18‑positive thecoma‑fibroma tumors.

Hypoxia‑inducible factor 1 (HIF‑1) activates the transcription of genes that act upon the adaptation of cancer cells to hypoxia. LW6, an HIF‑1 inhibitor, was hypothesized to improve resistance to cancer therapy in hypoxic tumors by inhibiting the accumulation of HIF‑1α. A clear anti‑tumor effect under low oxygen conditions would indicate that LW6 may be an improved treatment strategy for cancer in hypoxia. In the present study, the HIF‑1 inhibition potential of LW6 on the growth and apoptosis of A549 lung cancer cells in association with oxygen availability was evaluated. LW6 was observed to inhibit the expression of HIF‑1α induced by hypoxia in A549 cells at 20 mM, independently of the von Hippel‑Lindau protein. In addition, at this concentration, LW6 induced hypoxia‑selective apoptosis together with a reduction in the mitochondrial membrane potential. The intracellular reactive oxygen species levels increased in LW6‑treated hypoxic A549 cells and LW6 induced a hypoxia‑selective increase of mitochondrial O2•‑. In conclusion, LW6 inhibited the growth of hypoxic A549 cells by affecting the mitochondria. The inhibition of the mitochondrial respiratory chain is suggested as a potentially effective strategy to target apoptosis in cancer cells.

Background To date, the different treatment modalities for high-risk prostate cancer (Pca) have not been compared in any sufficiently large-scale, prospective, randomized clinical trial. We used propensity-score matching analysis to compare the oncological outcomes of high-risk prostate cancer between patients treated with radical prostatectomy (RP) and those treated with radiation therapy (RT). Methods We studied 216 patients who received neoadjuvant therapy followed by RP (RP cohort) and 81 patients who received neoadjuvant androgen-deprivation therapy (ADT) followed by RT (RT cohort). The RP cohort received a luteinizing hormone-releasing hormone agonist and estramustine phosphate (280 mg/day) for 6 months prior to RP. The RT cohort received ADT for at least 6 months prior to RT using a 3-dimensional conformal radiotherapy technique. The total radiation dose was 70 to 76 Gy administered at 2 Gy/fraction. Results Propensity-score matching identified 78 matched pairs of patients. The 3-year overall survival rates were 98.3% and 92.1% in the RP and RT groups, respectively (P = 0.156). The 3-year biochemical recurrence-free survival rates were 86.4% and 89.4% in the RP and RT groups, respectively (P = 0.878). Conclusions Our study findings may suggest almost identical cancer control of RP and RT with appropriate neoadjuvant therapy in high-risk Pca. Therefore, issues of health-related quality of life may have an important impact on decision making in treatment of high-risk Pca.

Between 1980 and 1994, 423 patients with esophageal cancer were given curative radiation therapy. Of these patients, 31 died of massive hemorrhage and were used as the subjects of analysis in this study. The incidence of massive hemorrhage in all patients was 7% (31/423). In the 31 patients who died of massive hemorrhage, 27 had local tumors and two had no tumors at hemorrhage (two unknown cases). The mean time interval from the start of radiation to hemorrhage was 9.2 months. In 9 autopsy cases the origin of hemorrhage was a tear of the aorta in 5 cases, necrotic local tumor in 3 cases and esophageal ulcer in 1 case. The positive risk factors for this complication seemed to be excess total dose, infection, metallic stent, and tracheoesophageal fistula. Chest pain or sentinel hemorrhage proceeding to massive hemorrhage was observed in about half of the patients.

We have investigated whether a hydrophilic photosensitizer, chlorin e6Na (Ce6Na), can sensitize cells to ionizing radiation. When V79-1 cells were pretreated with Ce6Na for 2 hr before receiving a dose of 2-14 Gy of irradiation, the cells became sensitive to X-irradiation. The sensitizing effect of Ce6Na depended on the dose of Ce6Na. The sensitizing effect also depended on the length of the treatment period before X-irradiation up to 4 hr, but not on the length of a treatment period after X-irradiation. Intracellular concentrations of Ce6Na were increased linearly after incubation with Ce6Na for periods of up to 4 h. The dose-modifying factor calculated from the survival curve was 1.25.

The aim of this study was to clarify the reliability of positron emission tomography (PET) using a new hypoxic cell tracer, 1-(2-[(18)F]fluoro-1-[hydroxymethyl]ethoxy)methyl-2-nitroimidazole ((18)F-FRP170).Twelve patients with glioblastoma underwent (18)F-FRP170 PET before tumor resection. Mean standardized uptake value (SUV) and normalized SUV were calculated at regions within a tumor showing high (high-uptake area) and relatively low (low-uptake area) accumulations of (18)F-FRP170. In these areas, intratumoral oxygen pressure (tpO2) was measured using microelectrodes during tumor resection.Mean tpO2 was significantly lower in the high-uptake area than in the low-uptake area. A significant negative correlation was evident between normalized SUV and tpO2 in the high-uptake area.The present findings suggest that high accumulation on (18)F-FRP170 PET represents viable hypoxic tissues in glioblastoma.

Background To evaluate prognostic factors in salvage radiotherapy (RT) for patients with pre-RT prostate-specific antigen (PSA) < 1.0 ng/ml. Methods Between January 2000 and December 2009, 102 patients underwent salvage RT for biochemical failure after radical prostatectomy (RP). Re-failure of PSA after salvage RT was defined as a serum PSA value of 0.2 ng/ml or more above the postradiotherapy nadir followed by another higher value, a continued rise in serum PSA despite salvage RT, or initiation of systemic therapy after completion of salvage RT. Biochemical relapse-free survival (bRFS) was estimated using the Kaplan-Meier method. Multivariate analysis was performed using the Cox proportional hazards regression model. Results The median follow-up period was 44 months (range, 11-103 months). Forty-three patients experienced PSA re-failure after salvage RT. The 4-year bRFS was 50.9% (95% confidence interval [95% CI]: 39.4-62.5%). In the log-rank test, pT3-4 (p < 0.001) and preoperative PSA (p = 0.037) were selected as significant factors. In multivariate analysis, only pT3-4 was a prognostic factor (hazard ratio: 3.512 [95% CI: 1.535-8.037], p = 0.001). The 4-year bRFS rates for pT1-2 and pT3-4 were 79.2% (95% CI: 66.0-92.3%) and 31.7% (95% CI: 17.0-46.4%), respectively. Conclusions In patients who have received salvage RT after RP with PSA < 1.0 ng/ml, pT stage and preoperative PSA were prognostic factors of bRFS. In particular, pT3-4 had a high risk for biochemical recurrence after salvage RT.

Ten roentgenographically-negative lung cancers were treated with radiation. All of the patients in this study were selected in a mass screening for lung cancer using sputum cytology, and their cancerous cells were confirmed as squamous cell carcinoma by bronchoscopic biopsy. Three tumors were proved to be multi-centric. Five patients were unresectable for medical reasons, three for the multi-centric occurrence, one for another advanced carcinoma and one for the refusal of surgery. The radiation field was confined into the primary tumor only, and a total dose of 6000cGy with a fraction size of 200cGy was delivered. Relapse was found in four patients; two inside the field and two outside the field. Local control rate was 75% of eight patients who were followed for more than 26 months. There was no mediastinal lymph node metastasis in seven patients. The radiation field for the roentgenographically-negative lung cancer may be confined at the primary tumor alone. However, careful follow-up should be continued because of the high incidence of multi-centric occurrence and subsequent additional lung cancer.

Prognostic factors in esophageal carcinoma treated with irradiation were examined. The prognosis of 111 patients without metastasis who had received more than 60 Gy was analyzed. Significant associations were found between survival rates and tumor length, stage, radioresponse of the primary tumor and the s.c. X-P classification based on barium contrast radiography; superficial type (tumor limited to the surface of the esophageal wall), tumorous type (solid mass without ulceration), Ul-A type (tumor with shallow ulceration with regular margin), Ul-B type (tumor with deep ulceration or irregular ulcer margin), and funneled type (tumor invading the esophageal wall in a scirrhous pattern). In multiple regression analysis, the X-P classification had the strongest correlation with survival and the survival rates of patients with the superficial type, the tumorous type and the s.c. Ul-A type were significantly higher than those of patients with the other tumor types (p < 0.001).