Efficacy and safety of preoperative chemoradiotherapy with S-1 for advanced rectal cancer: a phase II study.

Background: Preoperative chemoradiotherapy (CRT) for patients with rectal cancer is not yet established in Japan. We aimed to evaluate the efficacy and safety of preoperative CRT with S-1, a fixed-dose combination of tegafur, gimeracil, and oteracil potassium. Materials and methods: We conducted a prospective, interventional, non-randomized single-center study. Radiotherapy was administered at a total dose of 45 Gy (1.8 Gy in 25 fractions) for five weeks. S-1 was administered orally for nine weeks (five weeks during and four weeks after radiotherapy) at a dose of 80 mg/m2/day. The endpoint was the pathological complete response (pCR) rate. Results: Twenty-eight patients were finally enrolled. The following patient characteristics were recorded: clinical Stage (II: n = 12, III: n = 16), median age (66 years, range 40-77 years), male/female ratio (20/8), and lesion site (Ra-Rb:3/Rb:23/Rb-P:2). Preoperative treatment was completed in 27 patients (96%). Treatment abandonment occurred because of diarrhea. Grade 3 or higher adverse events were observed in one (4%) patient with two events. No serious adverse events occurred in the ≥ 70 years group. The response rate was 68% in all patients and 68% among elderly patients. Radical resection was achieved in all patients, including 19 (68%) who underwent sphincter-preserving surgery. The pCR rate was 11% (three patients). The five-year disease-free survival rate was 68%, and the overall survival rate was 82%. Local recurrence occurred in only one patient five years after surgery. Conclusion: Preoperative CRT with S-1 alone may be a safe and acceptable regimen from the perspective of adverse events and oncological outcomes. Trial registration: UMIN Clinical Trial Registry: UMIN000013598. Registered 1 April 2014, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recpt-no=R000015887.

Analyses of the local control of pulmonary Oligometastases after stereotactic body radiotherapy and the impact of local control on survival.

BACKGROUND: Successful local therapy for oligometastases may lead to longer survival. The purpose of this multicentre retrospective study was to investigate factors affecting the local control (LC) of pulmonary oligometastases treated by stereotactic body radiotherapy (SBRT) and to investigate the impact of LC on survival. METHODS: The inclusion criteria included 1 to 5 metastases, the primary lesion and other extrathoracic metastases were controlled before SBRT, and the biological effective dose (BED10) of the SBRT was 75 Gy or more. The Cox proportional hazards model was used for analyses. RESULTS: Data of 1378 patients with 1547 tumours from 68 institutions were analysed. The median follow-up period was 24.2 months. The one-year, 3-year and 5-year LC rates were 92.1, 81.3 and 78.6%, respectively, and the 1-year, 3-year and 5-year overall survival rates were 90.1, 60.3 and 45.5%, respectively. Multivariate analysis for LC showed that increased maximum tumour diameter (p = 0.011), type A dose calculation algorithm (p = 0.005), shorter overall treatment time of SBRT (p = 0.035) and colorectal primary origin (p < 0.001 excluding oesophagus origin) were significantly associated with a lower LC rate. In the survival analysis, local failure (p < 0.001), worse performance status (1 vs. 0, p = 0.013; 2-3 vs. 0, p < 0.001), oesophageal primary origin (vs. colorectal origin, p = 0.038), squamous cell carcinoma (vs. adenocarcinoma, p = 0.006) and increased maximum tumour diameter (p < 0.001) showed significant relationships with shorter survival. CONCLUSIONS: Several factors of oligometastases and SBRT affected LC. LC of pulmonary oligometastases by SBRT showed a significant survival benefit compared to patients with local failure.

Pulmonary Oligometastases Treated by Stereotactic Body Radiation Therapy: A Nationwide Survey of 1,378 Patients.

AIM: This study was performed to confirm the superior overall survival (OS) after pulmonary oligo-recurrence compared to pulmonary sync-oligometastases in a large nationwide study. PATIENTS AND METHODS: Patients that met the following criteria were included: 1 to 5 lung-only metastases at the beginning of stereotactic body radiation therapy (SBRT) was performed between January 2004 and June 2015, and the biological effective dose (BED) of SBRT was 75 Gy or more. The parameters included in the analyses were age, gender, ECOG PS, primary lesion, pathology, oligoetastatic state, SBRT date, chemotherapy before SBRT, chemotherapy concurrent SBRT, chemotherapy after SBRT, maximum tumor diameter, number of metastases, field coplanarity, dose prescription, BED10, OTT of SBRT. RESULTS: In total, 1,378 patients with 1,547 tumors were enrolled. Oligo-recurrence occurred in 1,016 patients, sync-oligometastases in 118, and unclassified oligometastases in 121. The three-year OS was 64.0% for oligo-recurrence and 47.5% for sync-oligometastasis (p<0.001). In the multivariate analysis, the hazard ratio (HR) for sync-oligometastases versus oligo-recurrence was 1.601 (p=0.014). Adverse events of Grade 5 were occurred in 3 patients. CONCLUSION: This is the first nationwide to indicate that the OS of patients with pulmonary oligo-recurrence is better than that of patients with sync-oligometastases.

Japanese structure survey of radiation oncology in 2012.

This paper describes the ongoing structure of radiation oncology in Japan in terms of equipment, personnel, patient load and geographic distribution to identify and overcome any existing limitations. From March 2013 to August 2016, the Japanese Society for Radiation Oncology conducted a questionnaire based on the Japanese national structure survey of radiation oncology in 2012. Data were analyzed based on the institutional stratification by the annual number of new patients treated with radiotherapy per institution. The estimated annual numbers of new and total (new plus repeat) patients treated with radiation were 213 000 and 251 000, respectively. Additionally, the estimated cancer incidence was 865 238 cases with ~24.6% of all newly diagnosed patients being treated with radiation. The types and numbers of treatment devices actually used included linear accelerator (LINAC; n = 864), telecobalt (n = 0), Gamma Knife (n = 44), 60Co remote afterloading system (RALS; n = 23) and 192Ir RALS (n = 130). The LINAC system used dual-energy functions in 651 units, 3D conformal radiotherapy functions in 759 and intensity-modulated radiotherapy (IMRT) functions in 466. There were 792 Japan Radiological Society/Japanese Society for Radiation Oncology-certified radiation oncologists, 1061.6 full-time equivalent (FTE) radiation oncologists, 2124.2 FTE radiotherapy technologists, 181.3 FTE medical physicists, 170.9 FTE radiotherapy quality managers and 841.5 FTE nurses. The frequency of IMRT use significantly increased during this time. In conclusion, the Japanese structure of radiation oncology has clearly improved in terms of equipment and utility although there was a shortage of personnel in 2012.

Japanese Structure Survey of Radiation Oncology in 2011.

We evaluated the evolving structure of radiation oncology in Japan in terms of equipment, personnel, patient load and geographic distribution to identify and overcome any existing limitations. From March 2012 to August 2015, the Japanese Society for Radiation Oncology conducted a questionnaire based on the Japanese national structure survey of radiation oncology in 2011. Data were analyzed based on the institutional stratification by the annual number of new patients treated with radiotherapy per institution. The estimated annual numbers of new and total (new plus repeat) patients treated with radiation were 211 000 and 250 000, respectively. Additionally, the estimated cancer incidence was 851 537 cases with approximately 24.8% of all newly diagnosed patients being treated with radiation. The types and numbers of treatment devices actually used included linear accelerator (LINAC; n = 836), telecobalt (n = 3), Gamma Knife (n = 46), 60Co remote afterloading system (RALS; n = 24), and 192Ir RALS (n = 125). The LINAC system used dual-energy functions in 619 units, 3D conformal radiotherapy functions in 719 and intensity-modulated radiotherapy (IMRT) functions in 412. There were 756 JRS or JASTRO-certified radiation oncologists, 1018.5 full-time equivalent (FTE) radiation oncologists, 2026.7 FTE radiotherapy technologists, 149.1 FTE medical physicists, 141.5 FTE radiotherapy quality managers and 716.3 FTE nurses. The frequency of IMRT use significantly increased during this time. To conclude, although there was a shortage of personnel in 2011, the Japanese structure of radiation oncology has clearly improved in terms of equipment and utility.

Japanese structure survey of radiation oncology in 2010.

We evaluated the evolving structure of radiation oncology in Japan in terms of equipment, personnel, patient load, and geographic distribution to identify and overcome any existing limitations. From March 2011 to June 2013, the Japanese Society for Radiation Oncology conducted a questionnaire based on the Japanese national structure survey of radiation oncology in 2010. Data were analyzed based on the institutional stratification by the annual number of new patients treated with radiotherapy per institution. The estimated annual numbers of new and total (new plus repeat) patients treated with radiation were 211 000 and 251 000, respectively. Additionally, the estimated cancer incidence was 805 236 cases, with ~26.2% of all newly diagnosed patients being treated with radiation. The types and numbers of treatment devices actually used included linear accelerator (LINAC; n = 829), telecobalt (n = 9), Gamma Knife (n = 46), 60Co remote afterloading system (RALS; n = 28), and 192Ir RALS (n = 131). The LINAC system used dual-energy functions in 586 units, three-dimensional conformal radiotherapy functions in 663, and intensity-modulated radiotherapy (IMRT) functions in 337. There were 564 JASTRO-certified radiation oncologists, 959.2 full-time equivalent (FTE) radiation oncologists, 1841.3 FTE radiotherapy technologists, 131.3 FTE medical physicists, 121.5 FTE radiotherapy quality managers, and 649.6 FTE nurses. The frequency of IMRT use significantly increased during this year. To conclude, although there was a shortage of personnel in 2010, the Japanese structure of radiation oncology has clearly improved in terms of equipment and utility.

[Five-Year Local Control by Stereotactic Body Radiation Therapy(SBRT)for Liver Metastasis from Colorectal Cancer-A Case Report].

An 84-year-old woman presented with a 9mm sized solitary liver metastasis in liver S8 18 months after the surgery for sigmoid colon cancer. The patient was treated with stereotactic body radiation therapy(SBRT)for local control, because the patient chose not to undergo surgery or chemotherapeutic treatment for metastatic liver cancer. SBRT is a minimally invasive treatment with a very short treatment period. Therefore, it may be considered as an alternative treatment for patients who are not suitable for surgery.

Case Series of 23 Patients Who Developed Fatal Radiation Pneumonitis After Stereotactic Body Radiotherapy for Lung Cancer.

The purpose of this study was to examine the characteristics and treatment plans of patients who experienced fatal radiation pneumonitis after stereotactic body radiation therapy for primary or oligometastatic lung cancer. Records of 1789 patients treated with stereotactic body radiation therapy for primary or oligometastatic lung cancer were retrospectively reviewed to identify those who developed fatal radiation pneumonitis. Twenty-three (1.3%; 18 men and 5 women) patients developed fatal radiation pneumonitis after stereotactic body radiation therapy for lung cancer; their median age was 74 years. The mean Krebs von den Lungen-6 level and percent vital capacity were 1320 U/mL and 82%, respectively. Prestereotactic body radiation therapy computed tomography revealed pulmonary interstitial change in 14 (73.7%) of 19 patients in whom computed tomography data could be reviewed. Seven (30.4%) of 23 patients had regularly used steroids. The median time duration between stereotactic body radiation therapy commencement and pneumonia symptom appearance was 75 (range: 14-204) days. Median survival time following pneumonia symptom appearance was 53 (range: 4-802) days. The 6- and 12-month overall survival rates were 34.8% and 13.0%, respectively. The 6-month overall survival rates in patients with and without heart disease were 50.0%, 16.7%, and 46.7% for heart disease existence, respectively. There were 4 patients in whom fatal radiation pneumonitis occurred within 2 months after stereotactic body radiation therapy and who died within 1 month. Three of them had no pulmonary interstitial change before stereotactic body radiation therapy, but had heart disease. In summary, the survival time in this case series was generally short but varied widely. More than half of the patients had pulmonary interstitial change before stereotactic body radiation therapy, although immediately progressive fatal radiation pneumonitis was also observed in patients without pulmonary interstitial change. True risk factors for fatal radiation pneumonitis should be examined in a prospective study with a larger cohort.

Improvement in the measurement error of the specific binding ratio in dopamine transporter SPECT imaging due to exclusion of the cerebrospinal fluid fraction using the threshold of voxel RI count.

OBJECTIVE: In Japan, the Southampton method for dopamine transporter (DAT) SPECT is widely used to quantitatively evaluate striatal radioactivity. The specific binding ratio (SBR) is the ratio of specific to non-specific binding observed after placing pentagonal striatal voxels of interest (VOIs) as references. Although the method can reduce the partial volume effect, the SBR may fluctuate due to the presence of low-count areas of cerebrospinal fluid (CSF), caused by brain atrophy, in the striatal VOIs. We examined the effect of the exclusion of low-count VOIs on SBR measurement. METHODS: We retrospectively reviewed DAT imaging of 36 patients with parkinsonian syndromes performed after injection of 123I-FP-CIT. SPECT data were reconstructed using three conditions. We defined the CSF area in each SPECT image after segmenting the brain tissues. A merged image of gray and white matter images was constructed from each patient's magnetic resonance imaging (MRI) to create an idealized brain image that excluded the CSF fraction (MRI-mask method). We calculated the SBR and asymmetric index (AI) in the MRI-mask method for each reconstruction condition. We then calculated the mean and standard deviation (SD) of voxel RI counts in the reference VOI without the striatal VOIs in each image, and determined the SBR by excluding the low-count pixels (threshold method) using five thresholds: mean-0.0SD, mean-0.5SD, mean-1.0SD, mean-1.5SD, and mean-2.0SD. We also calculated the AIs from the SBRs measured using the threshold method. We examined the correlation among the SBRs of the threshold method, between the uncorrected SBRs and the SBRs of the MRI-mask method, and between the uncorrected AIs and the AIs of the MRI-mask method. RESULTS: The intraclass correlation coefficient indicated an extremely high correlation among the SBRs and among the AIs of the MRI-mask and threshold methods at thresholds between mean-2.0D and mean-1.0SD, regardless of the reconstruction correction. The differences among the SBRs and the AIs of the two methods were smallest at thresholds between man-2.0SD and mean-1.0SD. CONCLUSION: The SBR calculated using the threshold method was highly correlated with the MRI-SBR. These results suggest that the CSF correction of the threshold method is effective for the calculation of idealized SBR and AI values.

The use of neoadjuvant therapy for resectable locally advanced thoracic esophageal squamous cell carcinoma in an analysis of 5016 patients from 305 designated cancer care hospitals in Japan.

BACKGROUND: Recent studies have shown the benefits of neoadjuvant therapy with chemotherapy or chemoradiotherapy for resectable locally advanced thoracic esophageal squamous cell carcinoma (ESCC). The aim of our study was to elucidate the use of neoadjuvant therapy for thoracic ESCC in Japan. METHODS: Data on patients with stage IB-III thoracic ESCC were retrieved from the national database of hospital-based cancer registries combined with claims data between 2012 and 2013. These data were analyzed using a mixed-effect logistic regression analysis, with a focus on exploring patterns in the first-line treatment for ESCC, including proportion of patients who received neoadjuvant therapy, and investigating the hospital characteristics and patient factors associated with the use of neoadjuvant therapy. RESULTS: Of the 5016 patients with stage IB-III thoracic ESCC at the 305 participating hospitals, 34.2% received neoadjuvant therapy (neoadjuvant chemotherapy, 29.5%; neoadjuvant chemoradiotherapy, 4.7%). The therapy was less likely to be administered to older patients (≤64 years, 48.8%; 65-70 years, 42.0%; 70-75 years, 33.9%; 75-80 years, 22.2%; 80-85 years, 3.8%; ≥85 years, 1.4%) and at hospitals with a low volume of patients (very high, 42.1%; high, 37.5%; low, 30.7%; and very low, 26.4%). This trend was confirmed by regression analysis. CONCLUSIONS: Based on our results, in Japan, relatively few patients with resectable locally advanced thoracic ESCC receive neoadjuvant therapy, with older patients and patients at lower volume hospitals being less likely than other patients to receive the neoadjuvant therapy. We recommend that the process of treatment decision-making be assessed at both the patient and hospital levels so that patients can consider various treatment options, including neoadjuvant therapy with surgery in Japan.

Re-irradiation for oligo-recurrence from esophageal cancer with radiotherapy history: a multi-institutional study.

BACKGROUND: Neoadjuvant chemoradiotherapy following surgery has recently become a standard therapy. The purpose of the present study was to determine the effectiveness and toxicity of re-irradiation for oligo-recurrence in lymph nodes from esophageal cancer treated by definitive radiotherapy or by surgery with additional radiotherapy. METHODS: We reviewed retrospectively 248 patients treated with (chemo)radiotherapy for oligo-recurrence in lymph nodes from esophageal cancer in five Japanese high-volume centers between 2000 and 2015. Thirty-three patients in whom re-irradiation was performed were enrolled in this study, and the results for patients in whom re-irradiation was performed were compared with the results for other patients. RESULTS: Median maximum lymph node diameter was 22 mm. Median total radiation dose was 60 Gy. The median calculated biological effective dose using the LQ model with α/ß = 10 Gy (BED10) in patients in whom re-irradiation was performed was significantly lower than the median BED10 in others. There was no different factor except for BED10, histology and irradiation field between patients with a past irradiation history and patients without a past irradiation history. The median observation period in surviving patients in whom re-irradiation was performed was 21.7 months. The 3-year overall survival rate in the 33 patients with a past irradiation history was 17.9%, with a median survival period of 16.0 months. Overall survival rate and local control rate in patients with a past irradiation history were significantly worse than those in patients without a past irradiation history (log-rank test, p = 0.016 and p = 0.0007, respectively). One patient in whom re-irradiation was performed died from treatment-related gastric hemorrhage. CONCLUSIONS: Results in the present study suggested that re-irradiation for oligo-recurrence in lymph nodes from esophageal cancer treated by definitive radiotherapy or by surgery with additional radiotherapy might be acceptable but unsatisfactory.

Definitive salvage radiation therapy and chemoradiation therapy for lymph node oligo-recurrence of esophageal cancer: a Japanese multi-institutional study of 237 patients.

BACKGROUND: This study evaluated the treatment results of lymph node (LN) oligo-recurrence in esophageal cancer patients treated with salvage radiotherapy (RT) in a multi-institutional retrospective study. METHODS: Eligibility criteria for this retrospective analysis were: the primary lesion of esophageal cancer was controlled; from one to five LN recurrences; total RT dose ≥45 Gy to exclude palliative RT; without recurrence other than LN; and salvage RT for LN recurrence was given between January 2000 and April 2015. The median follow-up time for the 93 living patients was 29.6 months. RESULTS: Two hundred thirty-seven patients were matched in five hospitals. The 3-year overall survival (OS) was 37%, local control was 45%, progression-free survival was 24%, and esophageal cancer-specific survival was 42%. On univariate analysis for OS, combined chemotherapy (p = 0.000055), disease-free interval (DFI) ≥12 months (p = 0.0013), LN max diameter ≤22 mm (p = 0.0052), and Karnofsky performance status ≥80% (p = 0.030) were associated with a significantly better prognosis. On multivariate analysis, significant differences were seen for combined chemotherapy (p = 0.000018), DFI (p = 0.0027), and LN max diameter (p = 0.018). CONCLUSIONS: LN oligo-recurrence following treatment for esophageal cancer was not a terminal-stage event. Moreover, cure may be possible by chemoradiation therapy with a long DFI (≥12 months) and small size (≤22 mm).

Lung stereotactic radiotherapy for oligometastases: comparison of oligo-recurrence and sync-oligometastases.

BACKGROUND: Oligometastases can be divided into sync-oligometastases and oligo-recurrence. The difference is whether the primary site is uncontrolled or controlled. The goal of this multicenter study was to evaluate treatment outcomes and factors affecting survival after stereotactic body radiotherapy for pulmonary oligometastases. METHODS: The information after stereotactic body radiotherapy from January 2004 to April 2014 was retrospectively collected. Ninety-six patients (65 males, 31 females) were enrolled. Ten cases (10%) were sync-oligometastases, 79 cases (82%) were oligo-recurrences and 7 (7%) were unclassified oligometastases with <6 months of disease-free interval. The median disease-free interval between initial therapy and stereotactic body radiotherapy was 24 months. The median calculated biological effective dose was 105.6 Gy. RESULTS: The median follow-up period was 32 months for survivors. The 3-year overall survival and relapse-free survival rates were 53% and 32%, respectively. No Grade 5 toxicity occurred. The median overall survival was 23.9 months for sync-oligometastases and 66.6 months for oligo-recurrence (P = 0.0029). On multivariate analysis, sync-oligometastases and multiple oligometastatic tumors were significant unfavorable factors for both overall survival and relapse-free survival. CONCLUSIONS: In stereotactic body radiotherapy for oligometastatic lung tumors, the state of oligo-recurrence has the potential of a significant prognostic factor for survival.

Patterns of prescribing radiotherapy and bevacizumab in nationwide practice - analysis of 101 designated cancer care hospitals in Japan.

Radiotherapy and bevacizumab are each effective in treating patients with advanced cancer, but their concurrent use may cause serious adverse events (SAEs). Whereas sequential administration can theoretically reduce the risk of SAEs while maintaining the anticancer effects, this hypothesis remains unconfirmed, leading to variations in practice. To elucidate current practices, the patterns of care received by patients in Japan with regard to these two therapies were assessed in a large database of a hospital-based cancer registry linked with insurance claims. This database contained information on 106 057 patients diagnosed with seven major cancers in 2011 and the care they received up to the end of 2012. In total, 335 patients from 101 hospitals in the database were treated with both radiotherapy and bevacizumab. Of these patients, 50.8% had lung cancer, and 51.3% had Stage IV cancer. Of the 335 patients, 75 (22.4%) received these therapies concurrently. In patients treated sequentially, the time from the last dose of bevacizumab to the start of radiotherapy was most frequently 4-5 weeks (12.4%), whereas the time from the end of radiotherapy to the start of bevacizumab was most frequently 1-2 weeks (10.6%). The cumulative proportions of patients in these two groups receiving sequential therapies within 3 weeks were 19.0% and 26.1%, respectively. Many practices appeared to avoid the concurrent use of bevacizumab and radiation, but some provided concurrent therapy. Additional data are required to determine whether the avoidance of concurrent use should become a standard of care.

Stereotactic Body Radiotherapy Results for Pulmonary Oligometastases: A Two-Institution Collaborative Investigation.

AIM: The current study investigated outcomes and prognostic factors of pulmonary oligometastases at two Institutions. PATIENTS AND METHODS: SBRT (stereotactic body radiotherapy) as performed for pulmonary oligometastases from January 2004 to April 2014, and patients with a biologically effective dose (BED10) ≥ 75 Gy were registered in the study. Control of the primary tumor was not a criterion: we included both oligo-recurrence and sync-oligometastases. RESULTS: A total of 34 patients were enrolled in the study. The median overall survival was 20 months (range=1-119 months) and the 2-year overall survival rate was 65.7% [95% confidence interval (CI)=48.3-83.1%]. The two-year local control rate was 79.1% (95% CI=62.4-95.8%). Stratified by oligo status, the 2-year overall survival rate of the oligo-recurrence group was 68.5% (95% CI=50.3-86.7%), while that of the group with sync-oligometastases was 50.0% (95% CI=1.0-99.0%). These rates were significantly different (p=0.037). No grade 5 early- or late-adverse events were recognized in the current study. CONCLUSION: SBRT for pulmonary oligometastases achieved good results and there was no serious adverse event. The oligo-recurrence group, in particular, achieved fairly good results.

Are hospitals in Japan with larger patient volume treating younger and earlier-stage cancer patients? An analysis of hospital-based cancer registry data in Japan.

OBJECTIVE: Differences in hospital case-mix have not been adequately accounted for in hospital volume and patient outcome studies in Japan. We aimed to examine whether differences may exist by investigating the distribution of patients' stage and age across designated cancer treatment hospitals of varying patient volume across Japan. METHODS: We analyzed data of gastric, breast, colorectal, lung and liver cancer patients who were included in the national database of hospital-based cancer registries between 2008 and 2011. We investigated the association between hospital volume, cancer stage and patient age. Hospitals were classified into five groups according to patient volume. RESULTS: In total, 676 713 patients met the inclusion criteria. The proportion of patients with early-stage (tumor-node-metastasis Stage 0 or I) cancer was higher among high-volume hospitals for all cancer types except small cell lung cancer. The proportion of older patients (age >75 years) was smaller among high-volume hospitals for all cancer types. The difference in the proportion of patients with early-stage cancers between very low-volume and very high-volume hospitals was greatest for non-small cell lung cancer (26.5% for very low and 43.5% for very high). This difference for the proportion of older patients was also greatest for non-small cell lung cancer (48.9% for very low and 30.3% for very high). CONCLUSIONS: We showed that the proportions of early-stage cancer patients and younger patients are greater in higher-volume hospitals compared with lower-volume hospitals in Japan. Researchers conducting volume-outcome studies and policymakers analyzing hospital performance should be cautious when making interhospital comparisons.

Factors that delay treatment of symptomatic metastatic extradural spinal cord compression.

BACKGROUND: Treatment delays of metastatic extradural spinal cord compression (MESCC) sometimes have been reported, but reasons for its delay have remained unclear. The purpose of this study was to assess which clinical factors are associated with treatment delays in neurologically symptomatic MESCC in the hospital settings. METHODS: We reviewed medical records of MESCC patients in our institute who had at least one progressive neurological symptom (weakness, sensory changes, urinary retention, or nerve root pain), were diagnosed by magnetic resonance imaging (MRI), and were treated with at least radiotherapy. The number of days prior to treatment initiation were counted and defined as follows: from the patients' first physician visit to our hospital until MRI diagnosis [T1 (days)], from MRI diagnosis to treatment [T2 (days)], and from patients' first visit to treatment [T1+2 (days)]. Nine clinical factors that could potentially delay treatment were analyzed for each period. RESULTS: Forty-three episodes of MESCC met the inclusion criteria. Median days in T1+2 was 3 days (range: 0-22). T1 and T1+2 were significantly higher in patients with normal walking status than in those with deterioration or inabilities to walk (T1+2, 7 days versus 3 days, median, p<0.001). The number of days was higher in all periods when it included weekends (T1+2, 7 days versus 2 days, median, p<0.001). CONCLUSIONS: Our findings suggest that normal walking status at the first physician visit and inclusion of weekends during the pretreatment periods were factors that resulted in treatment delays even for MESCC patients with emergency neurological symptoms.

Phase I trial of preoperative chemoradiation therapy with S-1 for low rectal cancer.

BACKGROUND/AIMS: A phase I study was performed to evaluate the dose-limiting toxicity and the recommended dose of the oral fluoropyrimidine S-1 when administered concurrently with radiation therapy to 9 Japanese patients with low rectal cancer. METHODOLOGY: S-1 was given orally for a total of 9 weeks (4 weeks alone and 5 weeks during radiation therapy) at oral doses of 65 mg/m2/day (n = 3 patients) or 80 mg/m2/day (n = 6 patients). Radiation therapy was administered in 1.5 gray fractions five times weekly (Monday to Friday) for a total dose of 45 gray. RESULTS: All patients achieved the planned 45 gray of radiation therapy. There was no grade > or = 3 toxicity. The recommended dose of S-1 was determined to be 80 mg/m2/ day. The dose intensity of S-1 was well maintained, and the combination of S-1 plus radiation therapy was well tolerated by all patients. Sphincter-preserving procedures were possible in all but one (89%) patient. High rates of tumor shrinkage and nodular downstaging were achieved. The histological response rate was 78%, including one complete response. CONCLUSIONS: The recommended dose of S-1 with concurrent radiation therapy was 80 mg/m2/day. Pre-operative chemoradiation therapy with S-1 was feasible and well tolerated by patients with low rectal cancer.

Non-invasive objective evaluation of radiotherapy-induced dry mouth.

BACKGROUND: Dry mouth is a common complaint in patients undergoing radiotherapy. Here, we employed the oral moisture meter Mucus III to evaluate dry mouth in head and neck tumor patients before and after they underwent radiotherapy. METHODS: We recruited 17 newly diagnosed patients with pharyngeal squamous cell carcinoma or unknown primary squamous cell carcinoma, who received head and neck radiation therapy at Tokyo University Hospital in 2008-2010. The primary sites were the epipharynx (n = 1), oropharynx (n = 6), or hypopharynx (n = 5); it was unknown in five cases. Salivary function was assessed by a dry mouth questionnaire, resting saliva test, chewing gum test, and Mucus III, before (n = 17), immediately after radiotherapy (n = 10), and at 3 (n = 9) and 12 months after radiotherapy (n = 11). RESULTS: The questionnaire, resting saliva test, and chewing gum test at 3 and 12 months after radiotherapy indicated a significantly decreased resting and stimulated whole saliva flow rate than prior radiotherapy (P < 0.05 and P < 0.001). In contrast, Mucus III results showed significant worsening of xerostomia at 12 months after radiotherapy (P < 0.05). CONCLUSION: Mucus III has been proven to be an objective diagnostic tool for patients with serious dry mouth, such as in patients with Sjogren's syndrome. However, we did not find a perfect correlation between Mucus III and other objective (resting saliva and chewing gum) and subjective (questionnaire) measures of dry mouth. To precisely diagnose radiotherapy-induced dry mouth, further improvement to the method is needed.

[Current situation and future prospects of radiotherapy for malignant gliomas].

Prognosis of malignant gliomas remains poor, although adjuvant radiotherapy increases survival time. To improve treatment outcomes, high-precision radiotherapy techniques such as three-dimensional conformal radiotherapy, stereotactic irradiation, intensity modulated radiotherapy, and charged particle radiotherapy have been developed for dose distribution optimization and dose escalation. Improvements in clinical outcomes with these new treatment strategies have been reported; however, the efficacy of these treatment strategies has not yet been verified in randomized trials. Further development of radiation delivery techniques, including boron neutron capture therapy, and ways of achieving more adequate target volume delineation using modern multimodality imaging technology are currently being intensively investigated to further improve patient outcomes.