Final analysis of a Multicenter Single-Arm Confirmatory Trial of hypofractionated whole breast irradiation after breast-conserving surgery in Japan: JCOG0906.

OBJECTIVE: To evaluate the safety and efficacy of hypofractionated whole breast irradiation for Asian women after breast-conserving surgery. This is an updated report with 5-year follow-up. METHODS AND MATERIALS: Asian women who had invasive breast cancer with clinical tumor size ≤3 cm, pN0-1c and negative inked margins were enrolled. Hypofractionated whole breast irradiation of 42.56 Gy/16 fractions was delivered, and boost irradiation of 10.64 Gy/4 fractions was added when the surgical margin was ≤5 mm. The primary endpoint was the proportion of grade ≥ 2 late adverse reactions within 3 years. Secondary endpoints included early adverse events, overall survival, disease-free survival, ipsilateral breast relapse-free survival, late adverse reactions and cosmetic outcome. Toxicities were evaluated using CTCAE ver3.0. Cosmetic outcomes were assessed using a 4-point scale and CTCAE ver3.0 for hyper/hypopigmentation, breast nipple/areolar deformity and breast volume/deformity. RESULTS: Between February 2010 and August 2012, 312 patients were enrolled, and 306 received hypofractionated whole breast irradiation. Median follow-up was 70.5 (range 7.6-88.9) months. The proportion of grade ≥ 2 late adverse reactions within 3 years was 4.3% (90% confidence interval 2.5-6.7%). Grade 2 early adverse events occurred in 38 (12.4%); none had grade 3/4. Five-year overall survival, disease-free survival and ipsilateral breast relapse-free survival were 98.7, 95.4 and 98.0%, respectively. Of the 304 evaluable patients, 29 (9.5%; 95% confidence interval 6.5-13.4%) had grade 2/3 late adverse reactions; none had grade 4/5. At 5 years, 70/289 (24.2%) showed any worsening of breast cosmetic changes. CONCLUSIONS: Hypofractionated whole breast irradiation is considered a standard treatment for Asian women with margin-negative invasive breast cancer after breast-conserving surgery.

A phase II study of adaptive two-step intensity-modulated radiation therapy (IMRT) with chemotherapy for loco-regionally advanced nasopharyngeal cancer (JCOG1015).

BACKGROUND: A phase II study of adaptive two-step intensity-modulated radiotherapy (IMRT) with chemotherapy for nasopharyngeal cancer (NPC) (JCOG1015) was conducted to evaluate the efficacy and safety. METHODS: Patients aged 20-75 years with stages II-IVB NPC were enrolled. As adaptive two-step IMRT, computed tomography planning was performed twice before IMRT for the initial plan of 46 Gy/23 fractions and during treatment for the boost plan of 24 Gy/12 fractions with a total dose of 70 Gy. Chemotherapy (cisplatin 80 mg/m2/3-weeks × 3 courses) was administered concurrently with IMRT, followed by adjuvant chemotherapy (cisplatin at 70 mg/m2 with 5-FU 700 at mg/m2 for 5 days/4 weeks × 3 courses). RESULTS: Between 2011 and 2014, 75 patients were enrolled from 12 institutions. The 3-year overall survival (OS) for the 75 patients was 88%, and the upper and lower limits of the 95% CI of 78%-94% were higher than the expected 3-year OS of 75% for the target population adjusted by the actual proportion of stage II:III:IV = 21%:44%:35%. The 3-year progression-free survival (PFS) and loco-regional PFS were 71% [59-80%] and 77% [66-85%], respectively. Although no grade 4-5 late toxicities were observed, 15 patients (20%) developed grade 3 late toxicities. Grade 2 xerostomia was noted in 26%, 12%, and 9% at 1, 2, and 3 years after starting IMRT, respectively. CONCLUSIONS: Adaptive two-step IMRT for NPC demonstrated an excellent 3-year OS with acceptable toxicities. This method may be one treatment option for locally advanced NPC.

A primary analysis of a multicenter, prospective, single-arm, confirmatory trial of hypofractionated whole breast irradiation after breast-conserving surgery in Japan: JCOG0906.

OBJECTIVE: To evaluate the safety of hypofractionated whole breast irradiation in Japanese women after breast-conserving surgery. METHODS: Japanese women who had invasive breast cancer with a clinical tumor size ≤3 cm, pN0-1c and a negative inked margin were enrolled. Hypofractionated whole breast irradiation (42.56 Gy/16 fractions) was delivered, adding boost irradiation (10.64 Gy/4 fractions) when the surgical margin was ≤5 mm. The treatment course was meant to be completed within 29 days or 33 days (plus boost irradiation). The primary endpoint was the proportion of grade ≥2 of pre-specified late adverse reactions, including telangiectasia, ulceration, fibrosis, fracture, pneumonitis, cardiac ischemia/infarction, pericardial effusion and breast pain, within 3 years. A sample size of 310 patients was set, with one-sided alpha of 0.05, beta of 0.1, threshold value of 8% and expected value of 4%. Secondary endpoints included the proportion of treatment completion within the recommended period and early adverse events within 90 days. Adverse events/adverse reactions were evaluated using CTCAE-3.0. RESULTS: Between 2010 and 2012, 312 women were enrolled; 306 received hypofractionated whole breast irradiation, but 6 chose conventional fractionated WBI, with 301 patients (96.5%) treated within the recommended period. Grade 2 early adverse events were found in 38 patients (12.4%); none had grade 3/4. Among the 303 evaluable patients, 13 (4.3%; 90% CI 2.6-6.7) had grade 2/3 late adverse reactions, including one with grade 3 pneumonitis, which was under the threshold value. CONCLUSION: Hypofractionated whole breast irradiation is considered to be safe and one of the standard treatments for Japanese women with margin-negative invasive breast cancer after breast-conserving surgery.

Factors associated with a preference for disclosure of life expectancy information from physicians: a cross-sectional survey of cancer patients undergoing radiation therapy.

PURPOSE: This study aimed to investigate experiences and preferences for disclosure of life expectancy, agreement between them, and the factors associated with preferences for disclosure of life expectancy with physicians among cancer patients undergoing radiation therapy. METHODS: Cancer patients aged 20 years or older were consecutively sampled when they started radiation therapy at two university hospitals. Patients completed self-administered questionnaires concerning their experiences of and preferences for disclosure of life expectancy, treatment decision-making, psychological distress, physical symptoms, sociodemographic and medical factors, physician's communication style, and provision of psychological, physical, and practical support. RESULTS: Among the 226 respondents (response rate: 58%) who responded, 54% experienced disclosure of life expectancy, and 45% preferred it. The agreement is 65%. Eighty-five percent recognized their aim of radiation therapy as curative. A univariate analysis indicated that having a full/part-time job and wishing to leave treatment decisions to doctors were significantly associated with preference for disclosure of life expectancy, but psychological distress was not. A multiple regression analysis revealed that having a full-time/part-time job was significantly associated with preference of communication about life expectancy. CONCLUSIONS: Fifty-four percent of the patients experienced and 45% of the patients preferred disclosure of life expectancy. The agreement is moderate. Our results show that there was a significant association between employment status and patient's preference for disclosure of life expectancy with physicians. Communication of prognosis is difficult but whether a patient continues to work or not may be an indicator of preference.

Regulatory mechanisms of hypoxia-inducible factor 1 activity: Two decades of knowledge.

Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator of various genes related to cellular adaptive responses to hypoxia. Dysfunctions in the regulatory systems of HIF-1 activity have been implicated in the pathogenesis of various diseases including malignant tumors and, thus, elucidating the molecular mechanisms underlying the activation of HIF-1 is eagerly desired for the development of novel anti-cancer strategies. The importance of oxygen-dependent and ubiquitin-mediated proteolysis of the regulatory subunit of HIF-1 (HIF-1α) was first reported in 1997. Since then, accumulating evidence has shown that HIF-1α may become stable and active even under normoxic conditions; for example, when disease-associated genetic and functional alterations in some genes trigger the aberrant activation of HIF-1 regardless of oxygen conditions. We herein review the last two decades of knowledge, since 1997, on the regulatory mechanisms of HIF-1 activity from conventional oxygen- and proteolysis-dependent mechanisms to up-to-the-minute information on cancer-associated genetic and functional alteration-mediated mechanisms.

Final report of survival and late toxicities in the Phase I study of stereotactic body radiation therapy for peripheral T2N0M0 non-small cell lung cancer (JCOG0702).

PURPOSE: A dose escalation study to determine the recommended dose with stereotactic body radiation therapy (SBRT) for peripheral T2N0M0 non-small cell carcinomas (JCOG0702) was conducted. The purpose of this paper is to report the survival and the late toxicities of JCOG0702. MATERIALS AND METHODS: The continual reassessment method was used to determine the dose level that patients should be assigned to and to estimate the maximum tolerated dose. The starting dose was 40 Gy in four fractions at D95 of PTV. RESULTS: Twenty-eight patients were enrolled. Ten patients were treated with 40 Gy at D95 of PTV, four patients with 45 Gy, eight patients with 50 Gy, one patient with 55 Gy and five patients with 60 Gy. Ten patients were alive at the last follow-up. Overall survival (OS) for all patients was 67.9% (95% CI 47.3-81.8%) at 3 years and 40.8% (95% CI 22.4-58.5%) at 5 years. No Grade 3 or higher toxicity was observed after 181 days from the beginning of the SBRT. Compared to the toxicities up to 180 days, chest wall related toxicities were more frequent after 181 days. CONCLUSIONS: The 5-year OS of 40.8% indicates the possibility that SBRT for peripheral T2N0M0 non-small cell lung cancer is superior to conventional radiotherapy. The effect of the SBRT dose escalation on OS is unclear and further studies are warranted.

Decreased acute toxicities of intensity-modulated radiation therapy for localized prostate cancer with prostate-based versus bone-based image guidance.

BACKGROUND: Intensity-modulated radiation therapy (IMRT) is a major therapeutic option for localized prostate cancer. Image-guided radiation therapy (IGRT) allows tumor visualization and corrects the errors caused by daily internal movement of the prostate. The current study retrospectively compared the acute toxicities and biochemical tumor control outcomes of prostate IMRT achieved using two IGRT techniques: bony structure-based IGRT (B-IGRT) and prostate-based IGRT (P-IGRT). METHODS: Between February 2011 and July 2014, 96 patients with low- or intermediate-risk prostate cancer were treated using P-IGRT based on cone-beam computed tomography (CBCT; 76 Gy) without fiducial markers. This group of patients was compared with a similar cohort of 96 patients who were treated with B-IGRT (74 Gy) between July 2007 and September 2011. The planning target volume (PTV) margins were 1-3 mm smaller in the P-IGRT group than in the B-IGRT group. RESULTS: The median follow-up periods for all patients, the P-IGRT group, and the B-IGRT group were 42, 32, and 64 months, respectively. A significantly lower incidence of acute grade 2 or higher gastrointestinal toxicities was observed in the P-IGRT group compared with the B-IGRT group (3 vs. 11%; p = 0.049). The prostate-specific antigen failure-free survival rates at 3 years were 95.5 and 92.7% for the P-IGRT and B-IGRT groups, respectively (p = 0.534). CONCLUSIONS: IMRT with P-IGRT allows PTV margin reduction without sacrificing tumor control, which successfully reduces acute rectal toxicity compared with IMRT with B-IGRT.

Five-year outcomes following hypofractionated stereotactic radiotherapy delivered in five fractions for acoustic neuromas: the mean cochlear dose may impact hearing preservation.

BACKGROUND: The aim of this study was to assess the clinical outcomes of acoustic neuromas (ANs) treated with hypofractionated stereotactic radiotherapy (hypo-FSRT) prescribed at a uniform dose. METHODS: Forty-seven patients with a unilateral AN were treated consecutively with hypo-FSRT between February 2007 and March 2012. Nineteen patients maintained a serviceable hearing status at the beginning of hypo-FSRT. The prescribed dose was 25 Gy delivered in five fractions per week to the isocenter, and the planning target volume was covered by the 80% isodose line. RESULTS: The median follow-up and audiometric follow-up periods were 61 and 52 months, respectively. The estimated tumor control rate at 5 years was 90% (95% CI 76-96). The existence of the cystic component before hypo-FSRT had a significantly worse impact on tumor control (p = 0.02). The estimated hearing preservation rates at 1, 3 and 5 years were 68% (95% CI 42-84), 41% (95% CI 20-62) and 36% (95% CI 15-57), respectively. A borderline significant difference was identified in the mean biological effective dose with an α/ß value of 3 Gy (BED3) to the ipsilateral cochlea between the preserved hearing and hearing loss groups (19 Gy vs. 28 Gy) (p = 0.08). CONCLUSIONS: Hypo-FSRT delivered in five fractions for unilateral ANs may achieve excellent tumor control with no severe facial or trigeminal complications. The mean BED3 in the cochlea may impact the hearing preservation rate. Therefore, the cochlear dose should be as low as possible.

Quality assurance of geometric accuracy based on an electronic portal imaging device and log data analysis for Dynamic WaveArc irradiation.

The purpose of this study was to develop a simple verification method for the routine quality assurance (QA) of Dynamic WaveArc (DWA) irradiation using electronic portal imaging device (EPID) images and log data analysis. First, an automatic calibration method utilizing the outermost multileaf collimator (MLC) slits was developed to correct the misalignment between the center of the EPID and the beam axis. Moreover, to verify the detection accuracy of the MLC position according to the EPID images, various positions of the MLC with intentional errors in the range 0.1-1 mm were assessed. Second, to validate the geometric accuracy during DWA irradiation, tests were designed in consideration of three indices. Test 1 evaluated the accuracy of the MLC position. Test 2 assessed dose output consistency with variable dose rate (160-400 MU/min), gantry speed (2.2-6°/s), and ring speed (0.5-2.7°/s). Test 3 validated dose output consistency with variable values of the above parameters plus MLC speed (1.6-4.2 cm/s). All tests were delivered to the EPID and compared with those obtained using a stationary radiation beam with a 0° gantry angle. Irradiation log data were recorded simultaneously. The 0.1-mm intentional error on the MLC position could be detected by the EPID, which is smaller than the EPID pixel size. In Test 1, the MLC slit widths agreed within 0.20 mm of their exposed values. The averaged root-mean-square error (RMSE) of the dose outputs was less than 0.8% in Test 2 and Test 3. Using log data analysis in Test 3, the RMSE between the planned and recorded data was 0.1 mm, 0.12°, and 0.07° for the MLC position, gantry angle, and ring angle, respectively. The proposed method is useful for routine QA of the accuracy of DWA.

Long-term outcomes of intensity-modulated radiotherapy following extra-pleural pneumonectomy for malignant pleural mesothelioma.

BACKGROUND: The purpose was to evaluate safety and efficacy of intensity-modulated radiotherapy (IMRT) following extra-pleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM). MATERIAL AND METHODS: Patients with MPM of clinical stage I-III, which were macroscopic completely resected with EPP were eligible for this prospective study. The ipsilateral hemithorax was irradiated with a prescribed dose of 50.4 Gy. When the high-risk surgical margins or FDG-avid regions were identified, simultaneous integrated boost (SIB) with 56.0 Gy or 61.6 Gy was applied. RESULTS: Twenty-one patients were enrolled. SIB was applied to five patients. The planned IMRT fractions were completed in all, but four patients who suffered from severe fatigue or radiation pneumonitis. With a potential median follow-up of 6.3 years, overall survival was 37.5% at 3 years since the IMRT. The median survival time was 17.5 and 27.0 months since the IMRT and the initial treatment, respectively. Three patients have survived for more than 5 years. Distant metastasis was observed in 15 patients. Local recurrence was also observed in 2 of the 15 patients. Acute toxicities of Grade 3 or worse were observed in 15 patients, including 9 with hematological, 3 with pneumonitis and 6 with fatigue, nausea or vomiting. Five patients developed Grade 3 or worse late toxicities associated with IMRT, consisting of one with persistent Grade 4 thrombocytopenia, one with brain infarction and congestive liver dysfunction, and three with elevation of serum transaminase or biliary enzyme. No Grade 5 toxicity was observed. Patients with N2 showed significantly worse survival than those with N0-1 (18.2% vs. 60.0% at 3 years, p = .014). CONCLUSION: IMRT following EPP achieved excellent local control for MPM, that might lead to the long-term survival in selected patients. However, treatment burden including acute and late toxicities should be considered in this treatment approach.

A randomized Phase III trial of comparing two dose-fractionations stereotactic body radiotherapy (SBRT) for medically inoperable Stage IA non-small cell lung cancer or small lung lesions clinically diagnosed as primary lung cancer: Japan Clinical Oncology Group Study JCOG1408 (J-SBRT trial).

A randomized Phase III trial commenced in Japan in February 2016. Currently, 42 Gy in four fractions of stereotactic body radiotherapy prescribed at the D95% of the planning target volume, which is considered equal to the commonly used 48 Gy in four fractions at the isocenter using an old dose calculation algorithm, is the standard treatment in Japan for medically inoperable Stage IA non-small cell lung cancer and small lung lesions clinically diagnosed as primary lung cancer. This study aims to examine the superiority of 55 Gy in four fractions over 42 Gy in four fractions. A total of 750 patients are expected to be accrued in 5 years. The primary endpoint is overall survival and the secondary endpoints are progression-free survival, local progression-free survival, patterns of failure, local control period, adverse events and serious adverse events. This trial is registered at the UMIN Clinical Trials Registry as UMIN000021029 (http://www.umin.ac.jp/ctr/index.htm) the dose covering 95% of the volume (D95%) of the planning target volume.

Severe esophagitis associated with cytomegalovirus during concurrent chemoradiotherapy for esophageal cancer.

Although radiation esophagitis is one of the most common adverse events that occurs during chemoradiotherapy (CRT) in patients with esophageal cancer, CRT-associated cytomegalovirus (CMV) esophagitis is rare. CMV esophagitis typically occurs in patients with an immunosuppressed status. Here we report a case of CMV esophagitis during CRT initially treated as radiation esophagitis. A 64-year-old man with mid-thoracic esophageal cancer was admitted to our hospital with clinical stage cT4bN1M1 (supraclavicular lymph node metastasis) Stage IV according to the UICC ver. 7 guidelines, and he was administered definitive concurrent CRT. From the 39th day of CRT onwards, he presented with a sustained fever and severe odynophagia that was resistant to antibiotic therapy. An esophagoscopy revealed severe esophagitis with a circumferential ulcer throughout the entire esophagus, and CMV esophagitis was clinically suspected because of positive result of CMV antigenemia. Subsequently, antiviral therapy for CMV provided dramatic relief of his symptoms. Later, CMV DNA was confirmed with a polymerase chain reaction in the biopsy specimen.The symptoms of CMV esophagitis resemble those of radiation esophagitis and can make the diagnosis difficult. Thus, CMV esophagitis associated CRT may be overlooked or masked by radiation esophagitis and can cause a delay in healing. Therefore, CMV esophagitis may be considered when severe intractable esophagitis is observed during CRT.

Estimation of the shielding ability of a tungsten functional paper for diagnostic x-rays and gamma rays.

Tungsten functional paper (TFP) is a novel paper-based radiation-shielding material. We measured the shielding ability of TFP against x-rays and gamma rays. The TFP was supplied in 0.3-mm-thick sheets that contained 80% tungsten powder and 20% cellulose (C6 H10 O5 ) by mass. In dose measurements for x-rays (60, 80, 100, and 120 kVp), we measured doses after through 1, 2, 3, 5, 10, and 12 TFP sheets, as well as 0.3 and 0.5 mm of lead. In lead equivalence measurements, we measured doses after through 2 and 10 TFP sheets for x-rays (100 and 150 kVp), and 0, 7, 10, 20, and 30 TFP sheets for gamma rays from cesium-137 source (662 keV). And then, the lead equivalent thicknesses of TFP were determined by comparison with doses after through standard lead plates (purity >99.9%). Additionally, we evaluated uniformity of the transmitted dose by TFP with a computed radiography image plate for 50 kVp x-rays. A single TFP sheet was found to have a shielding ability of 65%, 53%, 48%, and 46% for x-rays (60, 80, 100, and 120 kVp), respectively. The lead equivalent thicknesses of two TFP sheets were 0.10 ± 0.02, 0.09 ± 0.02 mmPb, and of ten TFP sheets were 0.48 ± 0.02 and 0.51 ± 0.02 mmPb for 100 and 150 kVp x-rays, respectively. The lead equivalent thicknesses of 7, 10, 20, and 30 sheets of TFP for gamma rays from cesium-137 source were estimated as 0.28, 0.43, 0.91, and 1.50 mmPb with an error of ± 0.01 mm. One TFP sheet had nonuniformity, however, seven TFP sheets provided complete shielding for 50 kVp x-rays. TFP has adequate radiation shielding ability for x-rays and gamma rays within the energy range used in diagnostic imaging field.

Estimation of lung tumor position from multiple anatomical features on 4D-CT using multiple regression analysis.

To estimate the lung tumor position from multiple anatomical features on four-dimensional computed tomography (4D-CT) data sets using single regression analysis (SRA) and multiple regression analysis (MRA) approach and evaluate an impact of the approach on internal target volume (ITV) for stereotactic body radiotherapy (SBRT) of the lung. Eleven consecutive lung cancer patients (12 cases) underwent 4D-CT scanning. The three-dimensional (3D) lung tumor motion exceeded 5 mm. The 3D tumor position and anatomical features, including lung volume, diaphragm, abdominal wall, and chest wall positions, were measured on 4D-CT images. The tumor position was estimated by SRA using each anatomical feature and MRA using all anatomical features. The difference between the actual and estimated tumor positions was defined as the root-mean-square error (RMSE). A standard partial regression coefficient for the MRA was evaluated. The 3D lung tumor position showed a high correlation with the lung volume (R = 0.92 ± 0.10). Additionally, ITVs derived from SRA and MRA approaches were compared with ITV derived from contouring gross tumor volumes on all 10 phases of the 4D-CT (conventional ITV). The RMSE of the SRA was within 3.7 mm in all directions. Also, the RMSE of the MRA was within 1.6 mm in all directions. The standard partial regression coefficient for the lung volume was the largest and had the most influence on the estimated tumor position. Compared with conventional ITV, average percentage decrease of ITV were 31.9% and 38.3% using SRA and MRA approaches, respectively. The estimation accuracy of lung tumor position was improved by the MRA approach, which provided smaller ITV than conventional ITV.

Optimization of Couch Modeling in the Change of Dose Calculation Methods and Their Versions.

In external radiotherapy, the X-ray beam passes through the treatment couch, leading to the dose reduction by the attenuation of the couch. As a method to compensate for the reduction, radiation treatment planning systems (RTPS) support virtual couch function, namely "couch modeling method". In the couch modeling method, the computed tomography (CT) numbers assigned to each structure should be optimized by comparing calculations to measurements for accurate dose calculation. Thus, re-optimization of CT numbers will be required when the dose calculation algorithm or their version changes. The purpose of this study is to evaluate the calculation accuracy of the couch modeling method in different calculation algorithms and their versions. The optimal CT numbers were determined by minimizing the difference between measured transmission factors and calculated ones. When CT numbers optimized by Anisotropic Analytical Algorithm (AAA) Ver. 8.6 were used, the maximum and the mean difference of transmission factor were 5.8% and 1.5%, respectively, for Acuros XB (AXB) Ver. 11.0. However, when CT numbers optimized by AXB Ver. 11.0 were used, they were 2.6% and 0.6%, respectively. The CT numbers for couch structures should be optimized when changing dose calculation algorithms and their versions. From the comparison of the measured transmission to calculation, it was found that the CT numbers had high accuracy.

Comparison of the pharmacokinetics between L-BPA and L-FBPA using the same administration dose and protocol: a validation study for the theranostic approach using [18F]-L-FBPA positron emission tomography in boron neutron capture therapy.

BACKGROUND: Boron neutron capture therapy (BNCT) is a cellular-level particle radiation therapy that combines the selective delivery of boron compounds to tumour tissue with neutron irradiation. L-p-Boronophenylalanine (L-BPA) is a boron compound now widely used in clinical situations. Determination of the boron distribution is required for successful BNCT prior to neutron irradiation. Thus, positron emission tomography with [18F]-L-FBPA, an 18F-labelled radiopharmaceutical analogue of L-BPA, was developed. However, several differences between L-BPA and [18F]-L-FBPA have been highlighted, including the different injection doses and administration protocols. The purpose of this study was to clarify the equivalence between L-BPA and [19F]-L-FBPA as alternatives to [18F]-L-FBPA. METHODS: SCC-VII was subcutaneously inoculated into the legs of C3H/He mice. The same dose of L-BPA or [19F]-L-FBPA was subcutaneously injected. The time courses of the boron concentrations in blood, tumour tissue, and normal tissue were compared between the groups. Next, we administered the therapeutic dose of L-BPA or the same dose of [19F]-L-FBPA by continuous infusion and compared the effects of the administration protocol on boron accumulation in tissues. RESULTS: There were no differences between L-BPA and [19F]-L-FBPA in the transition of boron concentrations in blood, tumour tissue, and normal tissue using the same administration protocol. However, the normal tissue to blood ratio of the boron concentrations in the continuous-infusion group was lower than that in the subcutaneous injection group. CONCLUSIONS: No difference was noted in the time course of the boron concentrations in tumour tissue and normal tissues between L-BPA and [19F]-L-FBPA. However, the administration protocol had effects on the normal tissue to blood ratio of the boron concentration. In estimating the BNCT dose in normal tissue by positron emission tomography (PET), we should consider the possible overestimation of the normal tissue to blood ratio of the boron concentrations derived from the values measured by PET on dose calculation.

Stereotactic body radiotherapy versus lobectomy for operable clinical stage IA lung adenocarcinoma: comparison of survival outcomes in two clinical trials with propensity score analysis (JCOG1313-A).

OBJECTIVE: No randomized controlled trials comparing stereotactic body radiotherapy and lobectomy for operable early-stage non-small-cell lung cancer have been successfully conducted. This study compared survival outcomes in two multi-institutional clinical trials for stereotactic body radiotherapy (Japan Clinical Oncology Group JCOG0403) and lobectomy (Japan Clinical Oncology Group JCOG0201) with propensity score analysis. METHODS: Inclusion criteria were operable, cT1N0M0 and adenocarcinoma diagnosed prior to registration of each trial. Forty of 169 patients from JCOG0403 and 219 of 811 patients from JCOG0201 were included. The primary endpoint was overall survival adjusted with propensity score analysis. The patient selection factors included in the logistic model to estimate the propensity score were age, sex, tumor diameter and consolidation/tumor ratio. RESULTS: Among patient selection factors, age distribution was quite different with little overlap: the median was 79 (interquartile range: 74.5-83.5) in stereotactic body radiotherapy and 62 (interquartile range: 55-68) in lobectomy. In propensity score analysis, 21 patients from each group were matched and the hazard ratio for stereotactic body radiotherapy over lobectomy was 9.00 (95% confidence interval: 1.14-71.04). In the post hoc subgroup analysis with propensity score analysis of inverse probability of treatment weighting, patients were limited to be aged 75 or younger because JCOG0201 only included them when aged 75 or younger. Thirteen patients for stereotactic body radiotherapy and 219 for lobectomy were compared, and the hazard ratio for stereotactic body radiotherapy over lobectomy was 1.19 (95% confidence interval: 0.38-3.73). CONCLUSIONS: The point estimates of hazard ratio favored lobectomy over stereotactic body radiotherapy in the limited number of patients. A randomized controlled study is needed for valid comparison.

Feasibility evaluation of hypofractionated radiotherapy with concurrent temozolomide in elderly patients with glioblastoma.

BACKGROUND: Although hypofractionated radiotherapy (HFRT) is preferred to conventionally fractionated radiotherapy when treating elderly patients with glioblastoma, the benefits and tolerability of HFRT with concurrent temozolomide (TMZ) remain unknown for such patients. We assessed the feasibility and outcomes of elderly patients with glioblastoma treated with HFRT and concurrent TMZ. METHODS: We retrospectively reviewed the medical records of 11 patients aged ≥70 years who were treated with HFRT and concurrent TMZ. All patients had newly diagnosed and histologically confirmed glioblastoma and were treated at our institution between October 2011 and April 2015. The median age was 74 years (range, 70-85 years). Total resection/subtotal resection/biopsy were performed in 2/5/4 patients, respectively. The planning target volume included the T1-enhancing tumor and the resection cavity plus 2-cm margins, and all surrounding edema. The median prescription dose was 35 Gy (range, 35-42.5 Gy), delivered in 10 fractions. Seven patients received TMZ at 150 mg/m2 for 5 days and 4 received TMZ at 75 mg/m2 during HFRT. Overall survival (OS) was defined as the time from surgery to death or the last follow-up. RESULTS: The median follow-up period was 13.2 months. The median OS and progression-free survival (PFS) times were 13.2 and 7.0 months, respectively. One patient experienced grade 4 neutropenia, lymphocytopenia, and thrombocytopenia. No grade 3 or higher nonhematological adverse event was noted. CONCLUSION: Our analysis demonstrated the feasibility of HFRT with concurrent TMZ used to treat elderly patients with glioblastoma. Further prospective clinical trials are needed to define therapies that balance efficacy with tolerability.

Clinical effect of multileaf collimator width on the incidence of late rectal bleeding after high-dose intensity-modulated radiotherapy for localized prostate carcinoma.

BACKGROUND: Several studies have confirmed a dosimetric advantage associated with use of a smaller leaf in intensity-modulated radiation therapy (IMRT). However, no studies have identified any clinical benefits. We investigated the effect of a smaller multileaf collimator (MLC) width on the onset of late rectal bleeding after high-dose prostate IMRT. MATERIALS AND METHODS: Two hundred and five prostate cancer patients were treated with a total dose of 78 Gy in 39 fractions by use of a dynamic MLC technique; however, two different MLC were used: a 10-mm-wide device and a 5-mm-wide device. Gastrointestinal toxicity and several clinical factors were assessed. RESULTS: The 5-year actuarial risk of grade 2 or higher rectal bleeding was 6.9 % for the 10-mm-wide group (n = 132) and 1.8 % for the 5-mm-wide group (n = 73) (p = 0.04). The median estimated rectal doses for the two groups were 55.1 and 50.6 Gy (p < 0.001), respectively. Univariate analysis showed that acute toxicity, rectal V30-60, median rectal dose, normal tissue complication probability (NTCP), and MLC type were significant predictive factors for late rectal toxicity. In multivariate analysis, acute toxicity and NTCP remained significant. CONCLUSION: In our planning approach for prostate IMRT, a decrease in MLC width from 10 to 5 mm contributed to further rectal dose reduction, which was the most important predictor of late rectal toxicity.

Identification of a predictive factor for distant metastasis in esophageal squamous cell carcinoma after definitive chemoradiotherapy.

BACKGROUND AND PURPOSE: Distant metastasis (DM) after definitive chemoradiotherapy has not been a focus of research in esophageal carcinoma. At present, local-regional control is improving following advances in salvage treatments after definitive chemoradiotherapy. There is a need to focus on suppressing the development of DM. The aim of this study was to identify pre-treatment factors associated with DM after definitive chemoradiotherapy. MATERIALS AND METHODS: This study included 144 patients with thoracic esophageal squamous cell carcinoma (Stage I/II/III/IV; 35/17/69/23) (TNM 7th) who underwent definitive chemoradiotherapy; >50 Gy was prescribed to all gross tumors with concurrent administration of 5-fluorouracil ± platinum. Pre-treatment factors included age, gender, performance status, tumor location, T/N/M status, tumor length, size of metastatic lymph nodes (LN size), and the presence of intramural metastasis or multiple primary tumors. The effects of pre-treatment factors on overall survival (OS) and DM were evaluated. RESULTS: The median follow-up period was 48 months. DM occurred as an initial progression in 21 % of patients, and LN size correlated with DM development (hazard ratio [HR] = 5.12; p = 0.0013) and poor OS (HR = 2.20; p = 0.0076) in univariate and multivariate analyses. CONCLUSIONS: LN size is a quantitative pre-treatment prognostic factor that should be assessed prior to definitive chemoradiotherapy. Patients with large metastatic lymph nodes are at high risk of DM and should be monitored.