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Background The feasibility of marker-less stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) has not yet been established, and, thus, was examined in the present study. Material and methods We retrospectively investigated patients who received marker-less SBRT for locally untreated HCC tumors between July 2005 and December 2018. Radiotherapy planning CT was performed under fixation with vacuum cushions and abdominal compression. The clinical target volume (CTV) was equivalent to the gross tumor volume (GTV). The internal target volume (ITV) margin to CTV was determined from calculations based on the motion of the diaphragm. The planning target volume (PTV) margin to ITV was 5-6 mm. In the set-up, radiotherapy planning CT and linac-integrated cone-beam CT performed in the same imaging and fixation settings were merged by referring to the anatomical components surrounding target tumors. The primary endpoint was the 3-year cumulative local tumor progression rate. The upper limit of the 95% confidence interval for the 3-year cumulative local tumor progression rate was less than 7.0%, which was interpreted as favorable local control and feasible for marker-less SBRT. Local tumor progression was assessed by mRECIST. Results We reviewed 180 patients treated with 35-40 Gy/5 fractions. The median follow-up time for the local tumor progression of censored tumors was 32.3 months (range, 0.3-104). The 3-year cumulative local tumor progression rate was 3.0% (95% CI, 1.1-6.5%). The 3-year overall survival rate was 71.6% (95% CI, 63.5-78.2%). Regarding acute hematologic toxicities, grade 3 hypoalbuminemia and thrombocytopenia were detected in 1 (0.6%) and 5 (2.9%) patients, respectively. Treatment-related death from SBRT was not observed. SBRT was initiated within 7 days after radiotherapy planning CT for 84% (152/180) of patients. Conclusions Marker-less SBRT for HCC achieved favorable local control that fulfilled the threshold. This result suggests that marker-less SBRT with appropriate settings is a feasible treatment strategy.

Background International guidelines recommend brachytherapy for patients with dysphagia from esophageal cancer, whereas brachytherapy is infrequently used to palliate dysphagia in some countries. To clarify the availability of palliative treatment for dysphagia from esophageal cancer and explain why brachytherapy is not routinely performed are unknown, this study investigated the use of brachytherapy and external beam radiotherapy for dysphagia from esophageal cancer. Methods Japanese Radiation Oncology Study Group members completed a survey and selected the treatment that they would recommend for hypothetical cases of dysphagia from esophageal cancer. Results Of the 136 invited facilities, 61 completed the survey (44.9%). Four (6.6%) facilities performed brachytherapy of the esophagus, whereas brachytherapy represented the first-line treatment at three (4.9%) facilities. Conversely, external beam radiotherapy alone and chemoradiotherapy were first-line treatments at 61 and 58 (95.1%) facilities, respectively. In facilities that performed brachytherapy, the main reason why brachytherapy of the esophagus was not performed was high invasiveness (30.2%). Definitive-dose chemoradiotherapy with (≥50 Gy) tended to be used in patients with expected long-term survival. Conclusions Few facilities routinely considered brachytherapy for the treatment of dysphagia from esophageal cancer in Japan. Conversely, most facilities routinely considered external beam radiotherapy. In the future, it will be necessary to optimize external beam radiotherapy.

Evidence regarding postoperative radiation therapy (PORT) for metastases to the long bones is lacking. Characterizing the current practice patterns and identifying factors that influence dose-fractionation schedules are essential for future clinical trials. An internet-based survey of the palliative RT subgroup of the Japanese Radiation Oncology Study Group was performed in 2017 to collect data regarding PORT prescription practices and dose-fractionation schedules. Responders were also asked to recommend dose-fractionation schedules for four hypothetical cases that involved a patient with impending pathological fractures and one of four clinical features (poor prognosis, solitary metastasis, radio-resistant primary tumor or expected long-term survival). Responders were asked to indicate their preferred irradiation fields and the reasons for the dose fractionation schedule they chose. Responses were obtained from 89 radiation oncologists (67 institutions and 151 RT plans) who used 22 dose-fractionation schedules, with the most commonly used and recommended schedule being 30 Gy in 10 fractions. Local control was the most common reason for preferring longer-course RT. High-dose fractionated schedules were preferred for oligometastasis, and low-dose regimens were preferred for patients with a poor prognosis; however, single-fraction RT was not preferred. Most respondents recommended targeting the entire orthopedic prosthesis. These results indicated that PORT using 30 Gy in 10 fractions to the entire orthopedic prosthesis is preferred in current Japanese practice and that single-fraction RT was not preferred. Oligometastasis and poor prognosis influenced the selection of high- or low-dose regimens.

Purpose Improving pain interference in daily activities, rather than mere pain reduction, is a desirable endpoint for palliative radiation therapy. The association between pain response and pain interference has been studied almost exclusively in patients with painful bone metastases (PBMs), whereas nonindex pain has scarcely been explored in palliative radiation therapy. We investigated whether index and nonindex pain endpoints are associated with pain interference changes in patients with both PBMs and painful non-bone-metastasis tumors (PNTs). Methods and Materials Brief pain inventory data collected at baseline and at 2 months post-treatment were used to calculate differences in pain interference scores. Pain response in terms of the index pain was assessed using the international consensus endpoint. Patients were diagnosed with predominance of other pain (POP) if nonindex pain of malignant or unknown origin was present and had a greater pain score than the index pain. Results Of 302 patients, 127 (42%) had PBMs and 175 (58%) had PNTs. The median pain interference score, which is based on the mean of the 7 subscale items, decreased to a greater extent among responders than among nonresponders (PBM group: –3.43 vs –0.57 [P = .005]; PNT group: –2.43 vs –0.29 [P < .001]). Moreover, patients without POP experienced a greater reduction in their median pain interference score than did those with POP (PBM group: –2.71 vs +0.43 [P = .004]; PNT group: –2.00 vs +1.57 [P = .007]). The Jonckheere-Terpstra test showed a significant trend across 4 pain response categories in patients with PBMs and those with PNTs (P < .001 for both). Conclusions The index and nonindex pain endpoints were positively and negatively associated with improvement in pain interference, respectively. There was no apparent difference between patients with PBMs and PNTs in terms of the associations of these endpoints with pain interference.

Highlights • The frequency of use of the ICT has risen in research for PBMs. • The frequency of the ICT use has been considerably limited for PNTs. • None of the journal articles had investigated non-index pain., Background and purpose Consistent assessment of the pain response is essential for adequately comparing treatment efficacy between studies. We studied the assessment of pain endpoints in radiotherapy for painful bone metastases (PBMs) and painful non-bone-metastasis tumors (PNTs). Material and methods We performed a literature search in the Green (Radiotherapy and Oncology) and Red (International Journal of Radiation Oncology * Biology * Physics) Journals for full-length original articles published between 2009 and 2018. We only included articles that assessed palliation of tumor-related pain after radiotherapy. The data obtained included the definitions of pain response and assessment of non-index pain (pain other than that related to the irradiated tumors). Results Among the 1812 articles identified using the journals’ search function, 60 were included in the analysis. Thirty percent of the PBM articles and approximately half of the PNT articles did not report on analgesic use. Among the prospective studies, 68% of the articles on PBMs and 10% of the articles on PNTs used the International Consensus Endpoint. The PBM articles published in 2014–2018 utilized the International Consensus Endpoint more frequently than those published in 2009–2013 (p = 0.049). No articles reported information on non-index pain. Conclusions After the initial publication of the International Consensus Endpoint, the frequency of its use appears to have risen in PBM research; however, its use in PNT studies has been considerably limited. The International Consensus Endpoint should be consistently utilized in future studies on radiotherapy for painful tumors. Since none of the journal articles had investigated non-index pain, this issue may also needs to be addressed.

The purpose of this study was to clarify the opinions of radiation oncologists in Japan regarding treatment for lung cancer complicated with interstitial lung disease (ILD) by a questionnaire survey, and the risk of acute exacerbation (AE) after radiotherapy. Questionnaires were sent to all of the facilities in which radiation therapy is performed for lung cancer in Japan by using the mailing list of the Japanese Society for Radiation Oncology (JASTRO). The questionnaire survey was conducted to clarify who judges the existence of ILD, the indications for radiation therapy in cases of ILD-combined lung cancer, and the ratio of ILD-combined lung cancer in lung cancer patients treated with radiation therapy. Patients with ILD-combined lung cancer who received radiotherapy during the period from April 2014 to March 2015 were retrospectively analysed. Any cases of AE without any other obvious cause were included. ILD confirmation was performed by central radiologists using computed tomography images. A total of 47 facilities responded to the questionnaire. Radiation therapy was an option in cases of ILD-combined lung cancer in 39 (83%) of the facilities. The indication for radiation therapy was based on image findings in 35 (90%) of the 39 facilities in which radiation therapy was acceptable or was a choice in some cases of ILD. The final indication was based on the opinion of the pulmonologist in 29 (74%) of those 39 facilities. In fiscal year 2014, a total of 2128 patients in 38 facilities received chest irradiation. Seventy-eight (3.7%) of those 2128 patients had ILD-combined lung cancer. Sixty-seven patients were included in patient analysis. AE occurred in 5 patients (7.5%), and one of those 5 patients (20.0%) died from radiation-induced AE. The median period from radiotherapy to AE was 4 months (range, 2–7 months). The following four independent risk factors for AE were identified in univariate analysis: non-advanced age (

Immune checkpoint inhibitors may enhance the efficacy of radiotherapy (RT) in cancer treatment but the effect remains unknown in metastatic gastric cancer (mGC). This study aimed to compare the tumor shrinkage by palliative RT for mGC patients with or without previous exposure to anti-PD-1 therapy. Data of 36 mGC patients who had received palliative RT from April 2013 to May 2019 were analyzed. Primary tumor responses were evaluated through a volumetric measurement-based method using computed tomography (CT) and endoscopic responses were evaluated in patients who underwent endoscopy before and after RT. Tumor microenvironment (TME) immune status was investigated by analyzing tumor-infiltrating lymphocytes by flow cytometry. Among 36 patients, 18 had previous exposure to anti-PD-1 before RT showing no significant differences in baseline characteristics with the other 18 patients without exposure to anti-PD-1 treatment. Tumor responses were observed in 28% (5/18) and none (0/18) in the anti-PD-1-exposed vs. naive group, respectively (P = 0.045). Five out of eight patients in the anti-PD-1-exposed group, who underwent endoscopy after RT showed partial response, but none in the anti-PD-1-naive patients showed response (P = 0.026). Increase in the CD8+ T cell/effector regulatory T cell ratio in TILs after anti-PD-1 therapy was noted in three responders to RT, but not in the other three non-responders. Prior exposure to anti-PD-1 therapy increases tumor response to RT. Immune profiling suggests that anti-PD-1 therapy may enhance the efficacy of RT by immunoactivation in the TME.

Palliative radiotherapy seems to be rarely performed for incurable gastric cancer. In this first multicenter study, we examined the effectiveness of palliative radiotherapy and investigated whether biologically effective dose (BED) is associated with survival, response, or re-bleeding. Eligibility criteria included blood transfusion or hemoglobin levels

PURPOSE/OBJECTIVE(S) In the largest prospective study to date, we examined the effectiveness of palliative radiation therapy for bleeding gastric cancer, and the association of the biologically effective dose (BED) with survival, bleeding response, or re-bleeding. MATERIALS/METHODS We recruited patients with incurable gastric cancer for whom palliative radiation therapy was planned. Eligibility criteria included blood transfusion or hemoglobin levels < 8.0 g/dL. The primary endpoint was the intention-to-treat (ITT) response rate at four weeks. Response entailed all of the following criteria: 1) hemoglobin levels ≥ 8.0 g/dL, 2) seven consecutive days from enrollment to blood sampling without blood transfusion, and 3) no salvage treatment (surgery, endoscopic treatment, transcatheter embolization, or reirradiation) for bleeding gastric cancer. Re-bleeding was defined as the need for blood transfusion or salvage treatment. Response was assessed at 2, 4, and 8 weeks after enrollment; re-bleeding was assessed monthly during the 6-month follow-up. Sample size was designed with the probability of obtaining a 90% confidence interval (CI) ≤ ± 15% being set at 0.8, assuming a per-protocol (PP) response rate of 70% at 4 weeks. RESULTS We enrolled 55 patients from 15 institutions. A median total radiation dose of 20 Gy (range, 8-45 Gy) was delivered in a median of five fractions. Of the 55 patients, 38 responded to treatment; of the 38 responders, 19 (50%) died and 12 (32%) experienced re-bleeding. The ITT response rates were 47%, 53% (95% CI, 39%-66%), and 49% at 2, 4, and 8 weeks, respectively. The PP response rates were 55%, 78%, and 90% at 2, 4, and 8 weeks, respectively. Restricted mean response and re-bleeding time up to 8 months were 2.3 months and 0.8 months, respectively. The median overall survival was 3.8 months (median follow-up, 12.1 months). The multivariable Cox model showed that neither response (a time-dependent covariate) (hazard ratio [HR], 1.04; 95% CI, 0.44-2.48) nor BED (alpha/beta = 10) (HR, 0.98; 95% CI, 0.95-1.02) were significant predictors of overall survival. The multivariable Fine-Gray model showed that BED was not a significant predictor of response (subdistribution HR, 1.02; 95% CI, 0.99-1.06). The univariable Cox model on transition hazard from response to re-bleeding showed that BED was not significantly associated with re-bleeding (HR, 0.98; 95% CI, 0.92-1.04). Grade 1, 2, 3, and ≥ 4 radiation-related adverse events were reported in 11, 9, 1, and 0 patients, respectively. CONCLUSION The PP bleeding response rate increased to 90% during the 8-week follow-up period. The frequent occurrence of death from shortly after enrollment lowered the ITT response rate and shortened the duration of response. BED was not significantly associated with survival, bleeding response, or re-bleeding.

OBJECTIVE This is an ancillary study of a multi-institutional randomized non-inferiority phase III trial of accelerated fractionation (AF) versus standard fractionation (SF) radiation therapy for T1-2N0M0 glottic cancer (JCOG0701). Biopsy specimens of tumors from the patients enrolled in the JCOG0701 are collected and the association between clinical outcomes and histopathologic features such as expression of epithelial cell adhesion molecule (EpCAM), p53, and p16 were investigated. METHODS Five slices of undyed slides from biopsy specimens were sent to the National Cancer Center Hospital and all the specimens were assessed for the expression of EpCAM, p53, and p16. The primary objective was to investigate the association between 3-year progression-free survival (PFS) and expression of EpCAM, p53, and p16. RESULTS A total of 88 out of 370 patients were enrolled in this ancillary study. The 3-year PFS for tumors with strong expression of EpCAM was 70.6% (95% CI 43.1%-86.6%), while that of tumors without strong expression of EpCAM was 77.5% (95% CI 65.9%-85.5%) with no remarkable difference between groups (P = .67). Likewise, there was no significant difference in 3-year PFS between tumors regardless of p53 or p16 status. However, in a subgroup analysis for 17 patients with a strong expression of EpCAM, AF showed better 3-year PFS than SF (100% vs 54.5%, P = .07). CONCLUSIONS From the current study, it could not be concluded that EpCAM, p16, and p53 were prognostic factors for early-stage glottic cancer after primary radiation therapy. AF might be an appropriate fractionation for tumors with a strong expression of EpCAM. LEVEL OF EVIDENCE 3 Laryngoscope, 131:1522-1527, 2021.

The purpose of this study was to compare hybrid intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (Hybrid IMRT/VMAT), with non-coplanar (nc) IMRT and nc-VMAT treatment plans for unresectable olfactory neuroblastoma (ONB). Hybrid IMRT/VMAT, nc-IMRT and nc-VMAT plans were optimized for 12 patients with modified Kadish C stage ONB. Dose prescription was 65 Gy in 26 fractions. Dose–volume histogram parameters, conformation number (CN), homogeneity index (HI), integral dose and monitor units (MUs) delivered per fraction were assessed. Equivalent uniform dose (EUD) and normal tissue complication probability (NTCP) based on the EUD model (NTCPLogit) and the Lyman–Kutcher–Burman model (NTCPLKB) were also evaluated. We found that the Hybrid IMRT/VMAT plan significantly improved the CN for clinical target volume (CTV) and planning treatment volume (PTV) compared with the nc-VMAT plan. In general, sparing of organs at risk (OARs) is similar with the three techniques, although the Hybrid IMRT/VMAT plan resulted in a significantly reduced Dmax to contralateral (C/L) optic nerve compared with the nc-IMRT plan. The Hybrid IMRT/VMAT plan significantly reduce EUD to the ipsilateral (I/L) and C/L optic nerve in comparison with the nc-IMRT plan and nc-VMAT plan, but the difference in NTCP between the three technique was

Background: Radiobiological model-based studies of photon-modulated radiotherapy for pancreatic cancer have reported reduced gastrointestinal (GI) toxicity, although the risk is still high. The purpose of this study was to investigate the potential of 3D-passive scattering proton beam therapy (3D-PSPBT) in limiting GI organ at risk (OAR) toxicity in localized pancreatic cancer based on dosimetric data and the normal tissue complication probability (NTCP) model.Methods: The data of 24 pancreatic cancer patients were retrospectively analyzed, and these patients were planned with intensity-modulated radiotherapy (IMRT), volume-modulated arc therapy (VMAT), and 3D-PSPBT. The tumor was targeted without elective nodal coverage. All generated plans consisted of a 50.4-GyE (Gray equivalent) dose in 28 fractions with equivalent OAR constraints, and they were normalized to cover 50% of the planning treatment volume (PTV) with 100% of the prescription dose. Physical dose distributions were evaluated. GI-OAR toxicity risk for different endpoints was estimated by using published NTCP Lyman–Kutcher–Burman (LKB) models. Analysis of variance (ANOVA) was performed to compare the dosimetric data, and ΔNTCPIMRT−PSPBT and ΔNTCPVMAT−PSPBT were also computed.Results: Similar homogeneity and conformity for the clinical target volume (CTV) and PTV were exhibited by all three planning techniques (P > 0.05). 3D-PSPBT resulted in a significant dose reduction for GI-OARs in both the low-intermediate dose range (below 30 GyE) and the highest dose region (Dmax and V50 GyE) in comparison with IMRT and VMAT (P < 0.05). Based on the NTCP evaluation, the NTCP reduction for GI-OARs by 3D-PSPBT was minimal in comparison with IMRT and VMAT.Conclusion: 3D-PSPBT results in minimal NTCP reduction and has less potential to substantially reduce the toxicity risk of upper GI bleeding, ulceration, obstruction, and perforation endpoints compared to IMRT and VMAT. 3D-PSPBT may have the potential to reduce acute dose-limiting toxicity in the form of nausea, vomiting, and diarrhea by reducing the GI-OAR treated volume in the low-to-intermediate dose range. However, this result needs to be further evaluated in future clinical studies.

This study aimed to evaluate the imaging findings and prognostic factors after whole-brain radiotherapy in patients with carcinomatous meningitis from breast cancer. A retrospective analysis of imaging data and prognostic factors was performed in patients treated with whole-brain radiotherapy or whole-brain/spine radiotherapy immediately after the first diagnosis of carcinomatous meningitis from breast cancer at our hospital from January 1, 2010 to December 31, 2018. Statistical significance was set at P

Background The purpose of this study was to determine the potential of escalated dose radiation (EDR) robust intensity-modulated proton radiotherapy (ro-IMPT) in reducing GI toxicity risk in locally advanced unresectable pancreatic cancer (LAUPC) of the head in term of normal tissue complication probability (NTCP) predictive model. Methods For 9 patients, intensity-modulated radiotherapy (IMRT) was compared with ro-IMPT. For all plans, the prescription dose was 59.4GyE (Gray equivalent) in 33 fractions with an equivalent organ at risk (OAR) constraints. Physical dose distribution was evaluated. GI toxicity risk for different endpoints was estimated using published NTCP Lyman Kutcher Burman (LKB) models for stomach, duodenum, small bowel, and combine stomach and duodenum (Stoduo). A Wilcoxon signed-rank test was used for dosimetry parameters and NTCP values comparison. Result The dosimetric results have shown that, with similar target coverage, ro-IMPT achieves a significant dose-volume reduction in the stomach, small bowel, and stoduo in low to high dose range in comparison to IMRT. NTCP evaluation for the endpoint gastric bleeding of stomach (10.55% vs. 13.97%, P = 0.007), duodenum (1.87% vs. 5.02%, P = 0.004), and stoduo (5.67% vs. 7.81%, P = 0.008) suggest reduced toxicity by ro-IMPT compared to IMRT. ∆NTCP IMRT – ro-IMPT (using parameter from Pan et al. for gastric bleed) of ≥5 to ro-IMPT/NTCPIMRT) reduction was noted (0.16–0.81) for all GI-OARs except for duodenum (> 1) with endpoint grade ≥ 3 GI toxicity (using parameters from Holyoake et al.). Conclusion With similar target coverage and better conformity, ro-IMPT has the potential to substantially reduce the risk of GI toxicity compared to IMRT in EDR of LAUPC of the head. This result needs to be further evaluated in future clinical studies.

Purpose Palliative radiotherapy is the standard of care for bone metastases. However, skeletal-related events, defined as a pathologic fracture, paraplegia, surgery or radiotherapy for local recurrence, or severe pain in previously irradiated bone with radio-resistant histology type still present high incidence. The primary objective of this study was to determine whether zoledronic acid hydrate and palliative radiotherapy could prevent local skeletal-related events. Methods Eligible patients with bone metastases from renal cell carcinoma were treated with zoledronic acid hydrate every 3 or 4 weeks and concurrent palliative radiotherapy of 30 Gy in 3 Gy fractions. The criteria for radiotherapy were established by the treating physician, but patients with complicated bone metastases (impending pathological fracture or spinal cord compression) which needed immediate surgery were excluded. The primary endpoint was the local skeletal-related event-free survival rate at 1 year. Results Twenty-seven patients were included in the study. The median age was 65 (range, 50–84) years. Radiotherapy dose was 30 Gy for all patients except 1 whose radiotherapy was terminated due to brain metastasis progression at 18 Gy. Zoledronic acid hydrate was administered in a median of 12 (range, 0–34) times. The median follow-up period was 12 months and 19 months in patients who were still alive. Of 27 patients in the efficacy analysis, the 1-year local skeletal-related event-free rate was 77.6% (80% confidence interval, 66.2–89.0). Common grade 3 toxicities were hypocalcemia (1 [4%]), sGPT level increase (1 [4%]) and sGOT level increase (1 [4%]). There was no grade 4 or 5 toxicity. Conclusion Zoledronic acid hydrate administration and palliative radiotherapy were a well-tolerated and promising treatment reducing skeletal-related events for bone metastases from renal cell carcinoma.

This study sought to evaluate the impact of prophylactic cranial irradiation (PCI) on the pattern of brain recurrence after radical treatment in patients with limited-disease small-cell lung cancer (LD-SCLC). Patients treated with radiotherapy and chemotherapy between January 2006 and December 2014 at a single institution were retrospectively examined. Radiotherapy was performed using accelerated hyperfractionated radiotherapy (twice daily, 45 Gy in 30 fractions) or conventional fractionated radiotherapy (once daily, 50 Gy in 25 fractions). The chemotherapy regimen consisted of intravenous platinum–etoposide. A total of 162 patients were included and the median follow-up duration was 38 months. Ninety-three patients underwent PCI, and the 3-year overall survival (OS) rates were 14% among patients without PCI and 41% among those with PCI (P < 0.001). The frequency of brain metastases as a first recurrence site (BMFR) was significantly lower among patients who underwent PCI, compared with those who did not (P = 0.002). The median time to the l of BMFR was significantly shorter among patients without PCI than among those with PCI (P = 0.012). In addition, 68% of the BMFR patients who did not undergo PCI exhibited five or more lesions, while only 12% of BMFR patients who did undergo PCI exhibited five or more lesions (P < 0.001). PCI had a significant positive impact on patient prognosis after radical treatment for LD-SCLC, and the difference in the number of, and time to the appearance of, BMFR between patients treated with PCI and those treated without PCI might affect the clinical outcomes.

Some patients undergoing breast reconstruction require post-mastectomy radiation therapy, but the metallic ports used in temporary tissue expanders attenuate the X-rays. In this study, we evaluated by the film method, the attenuation of 4 MV and 6 MV X-rays after passing through a metallic port, with the aim of identifying a useful method for determining the appropriate density to use in the radiation treatment planning system (RTPS), taking into account the distance between the metallic port and the targets. Radiochromic film was used to measure depth doses after the X-rays passed through the metallic port. The physical density allotted to the metal port portion was varied on the RTPS within the range 1–16 g/cm3, and the physical density values were calculated that best reproduced the depth–dose distribution extrapolated from the film method. When the metallic port was orientated perpendicularly, the attenuation of the X-rays peaked at ~7% at both 4 MV and 6 MV. In the parallel orientation, the X-rays were attenuated by up to ~40% at 4 MV and by up to ~30% at 6 MV. We estimated the optimum physical density to be 9.8 g/cm3, which yielded the best fit with the actual measurements. We demonstrated the most likely range for the target depth from the CT images of actual patients and, within this range, we identified the optimum physical density at which the measured and calculated values were most consistent with each other.

We conducted a retrospective, nationwide multicenter study to evaluate the clinical outcomes of proton beam therapy for bone sarcomas of the skull base and spine in Japan. Eligibility criteria included: (i) histologically proven bone sarcomas of the skull base or spine; (ii) no metastases; (iii) ≥20 years of age; and (iv) no prior treatment with radiotherapy. Of the 103 patients treated between January 2004 and January 2012, we retrospectively analyzed data from 96 patients who were followed-up for >6 months or had died within 6 months. Seventy-two patients (75.0%) had chordoma, 20 patients (20.8%) had chondrosarcoma, and four patients (7.2%) had osteosarcoma. The most frequent tumor locations included the skull base in 68 patients (70.8%) and the sacral spine in 13 patients (13.5%). Patients received a median total dose of 70.0 Gy (relative biological effectiveness). The median follow-up was 52.6 (range, 6.3–131.9) months. The 5-year overall survival, progression-free survival, and local control rates were 75.3%, 49.6%, and 71.1%, respectively. Performance status was a significant factor for overall survival and progression-free survival, whilst sex was a significant factor for local control. Acute Grade 3 and late toxicities of ≥Grade 3 were observed in nine patients (9.4%) each (late Grade 4 toxicities [n = 3 patients; 3.1%]). No treatment-related deaths occurred. Proton beam therapy is safe and effective for the treatment of bone sarcomas of the skull base and spine in Japan. However, larger prospective studies with a longer follow-up are warranted.

To clarify the efficacy and toxicity of post-mastectomy radiation therapy (PMRT) without usage of a bolus, we identified 129 consecutive patients who received PMRT at the National Cancer Center Hospital East between 2003 and 2012. Seven of the 129 patients who received breast reconstruction before PMRT were excluded. All patients received PMRT of 6 MV photons, without usage of a bolus. The median follow-up duration for all eligible patients was 47.7 months (range: 4.0–123.2). Local, locoregional and isolated locoregional recurrence was found in 12 (9.8%), 14 (11%) and 5 patients (4.1%), respectively. The 3- and 5-year cumulative incidence of local recurrence, locoregional recurrence and isolated locoregional recurrence was 9.2 and 10.7%, 10.8 and 12.4%, and 4.3 and 4.3%, respectively. Although Grade 2 dermatitis was found in 11 patients (9.0%), no Grade 3–4 dermatitis was found. On univariate analysis, only a non-luminal subtype was a significant predictor for local recurrence (P

To clarify the frequency and predictors of detecting early locoregional recurrence/disease progression (LR/DP) during the interval between surgery and postoperative adjuvant radiotherapy with/without chemotherapy in patients with oral squamous cell carcinoma. Data on 65 patients who had undergone the initial radical surgery for previously untreated oral squamous cell carcinoma which were scheduled to receive adjuvant radiotherapy with/without chemotherapy were reviewed. Of the 65 patients, 63 (97%) were margin-positive/close and/or extracapsular extension-positive (hereinafter, high-risk factors). Eighteen (28%) patients had abnormal findings suggestive of LR/DP on postoperative imaging. Fifteen (23%) patients were diagnosed with LR/DP and treatment policy was changed. Univariate and multivariate analyses revealed higher frequencies of abnormal findings suggestive of LR/DP (univariate/multivariate analysis, p = 0.020/0.036), diagnosing of LR/DP, and changing the treatment policy (univariate/multivariate analysis, p = 0.042/0.046), among the patients who underwent postoperative diagnostic imaging tests or radiotherapy-planning contrast-enhanced (CE) CT without diagnostic imaging tests as compared with those who underwent radiotherapy-planning non-CECT without such tests. The frequency of detecting of early LR/DP before postoperative adjuvant treatment in oral squamous cell carcinoma patients with high-risk factors was high. Furthermore, postoperative diagnostic imaging tests and radiotherapy-planning CECT may be useful to detect early LR/DP in oral squamous cell carcinoma patients before postoperative adjuvant therapy.

INTRODUCTION To clarify the efficacy and safety of hypofractionated proton beam therapy (PBT) for centrally located lung cancer. METHODS We retrospectively reviewed 39 patients who received hypofractionated [≧3 Gy (relative biological effectiveness: RBE)/fraction] PBT for centrally located cT1-2N0M0 (8th edition) lung cancer between 1999 and 2015. A tumour within 2 cm of the proximal bronchial tree was defined as a centrally located tumour. RESULTS Twenty-four patients (62%) were treated with 80 Gy (RBE) in 20 fractions (112 Gy10 ), whereas eight (21%) were treated with 66 Gy (RBE) in 10 fractions (109.56 Gy10 ). The median follow-up period for censored patients was 48 months (range: 4-140). The 2-year progression-free survival (PFS) and overall survival (OS) rates were 86 and 100% for T1 disease and 56 and 94% for T2 disease, respectively. Patients who received 110 Gy10 or higher showed significantly better PFS than those who received less than 110 Gy10 , while no significant difference was noted in OS between the two groups. The sites of the first progression were local in six patients (27%), regional in seven (32%), distant in seven (32%), and local and distant in two (9%). Among the 13 patients with loco-regional recurrence, only two (15%) received treatments with curative intent. Dyspnoea of grade 3 was noted in one patient (3%), and pneumonitis of grade 2 was noted in four patients (10%). CONCLUSION Hypofractionated PBT may be a very safe and effective treatment option for centrally located early lung cancer.

OBJECTIVE To evaluate the feasibility of postoperative intensity-modulated radiotherapy for head and neck cancer by investigating the patterns of failure after this therapy. METHODS A retrospective chart review was performed. RESULTS Between March 2006 and December 2013, 122 consecutive patients with head and neck squamous cell carcinoma were treated by surgery followed by postoperative intensity-modulated radiotherapy. In regard to the site of the primary tumor, 59 (48%) patients had cancer of the oral cavity, 31 (26%) patients had cancer of the hypopharynx, 14 (11%) patients had cancer of the oropharynx, 10 (8%) patients had cancer of the larynx and 8 (7%) patients had cancer of unknown primary. The median follow-up period of the surviving patients was 54 months (range, 25-115). Concurrent chemotherapy was administered in 76 patients (62%). The median prescribed radiation dose was 66 Gy. The 3-year overall survival, progression-free survival, distant metastasis free survival and loco-regional control rates were 59%, 48%, 52.4% and 71%, respectively. Of the 122 patients, 32 developed loco-regional recurrence as the initial recurrence, including in-field recurrence in 26 patients, marginal recurrence in five patients and out-field recurrence in seven patients. Of the five patients with marginal recurrence, four have had two or more surgeries before the intensity-modulated radiotherapy and three had oral cavity cancer. Severe adverse events were not frequent, occurring at a frequency of

100 Background: Chemoradiotherapy (CRT) followed by curative resection in patients (pts) with local recurrence after radical surgery for primary rectal cancer is the preferred strategy if radiotherapy (RT) was not previously performed. In VOLTAGE-A study, nivolumab plus surgery following CRT showed a promising pathologic complete response (pCR) rate of 30% in pts with microsatellite-stable (MSS) advanced primary rectal cancer. The treatment sequence was prospectively investigated in pts with Locally Recurrent Rectal Cancer (LRRC) in VOLTAGE-B. Methods: Pts with pelvic LRRC without previous RT were included. Five cycles of nivolumab (240 mg q2 weeks) plus curative surgery following CRT (50.4 Gy with capecitabine 1,650 mg/m2) were performed. The pCR rate using AJCC tumor regression grading and curative resection rate were key endpoints. Planned sample size in VOLTAGE-B was set 10 pts in an exploratory manner. Results: From May to Oct 2018, 10 pts were included. Median age was 65 and 8 were male. Curative resection was performed in nine pts with MSS. One had a newly diagnosed supraclavicular lymph node metastasis before surgery. As one pt with AJCC grade 0, seven with grade 2, and one with grade 3, were observed, pCR rate was 10%. As of cut-off date of Apr 2019, three pts showing recurrence out of the nine pts were observed. Nivolumab-related adverse events (AEs) were only one pt with grade 1 hyperthyroidism and one with grade 1 erythema. Grade 3/4 surgery-related AEs were observed in six pts, including two pts with ileus and two with pelvic infections. No treatment-related deaths were observed. Conclusions: The pCR rate of 10% with acceptable toxicity was shown in MSS LRRC pts treated with nivolumab plus curative surgery following CRT. Translational research exploring better predictors of efficacies of study treatment are ongoing. Clinical trial information: NCT02948348.

Background The purpose of this study was to perform a dosimetric comparison between proton beam therapy (PBT) and photon radiation therapy in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who were treated with PBT in our institution. In addition, we evaluated the correlation between toxicities and dosimetric parameters, especially the doses to normal lung or heart tissue, to clarify the clinical advantage of PBT over photon radiation therapy. Methods A total of 37 consecutive patients with Stage III thoracic ESCC who had received PBT with or without concurrent chemotherapy between October 2012 and December 2015 were evaluated in this study. The dose distributions of PBT were compared with those of dummy 3-dimensional conformal radiation therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT), focusing especially on the doses to organs at risk, such as normal lung and heart tissue. Results Of the 37 patients, the data from 27 patients were analyzed. Among these 27 patients, four patients (15%) developed grade 2 pericardial effusion as a late toxicity. None of the patients developed grade 3 or worse acute or late pulmonary and cardiac toxicities. When the dosimetric parameters between PBT and planned 3DCRT were compared, all the PBT domestic variables for the lung dose except for lung V10 GyE and V15 GyE were significantly lower than those for the dummy 3DCRT plans, and the PBT domestic variables for the heart dose were also significantly lower than those for the dummy 3DCRT plans. When the PBT and IMRT plans were compared, all the PBT domestic variables for the doses to the lung and heart were significantly lower than those for the dummy IMRT plans. Regarding the correlation between the grades of toxicities and the dosimetric parameters, no significant correlation was seen between the occurrence of grade 2 pericardial effusion and the dose to the heart. Conclusions When the dosimetric parameters of the dose distributions for the treatment of patients with locally advanced stage III ESCC were compared between PBT and 3DCRT or IMRT, PBT enabled a significant reduction in the dose to the lung and heart, compared with 3DCRT or IMRT.

Congenital tracheal stenosis (CTS) is a rare disorder almost always diagnosed in infancy due to respiratory failure and other cardiopulmonary abnormalities. We experienced a 42-year-old female undiagnosed with CTS until difficult intubation upon surgery. Chest X-ray and computed tomography (CT) images revealed bronchial narrowing, which could already be seen prior to intubation, but was left unnoticed. Difficult airway management is a potentially lethal airway emergency. This life-threatening situation is preventable with the appropriate awareness. We report this clinically valuable case for the safety of future patient care. In English and Japanese literature, there are only 12 reported cases of CTS diagnosed in the adult. Ours and six previous cases were discovered with difficult intubation, a preventable life-threatening airway emergency. Pre-intubation images should be examined carefully for the possibility of CTS, as its frequency may be underestimated. Moreover, in treatment resistant recurrent asthmatic episodes, CTS should be kept in mind.

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.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.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, p0.001). The number of days was higher in all periods when it included weekends (T1+2, 7 days versus 2 days, median, p0.001).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.

Drug resistance often critically limits the efficacy of molecular targeted drugs. Although pharmacological inhibition of phosphatidylinositol 3-kinase (PI3K) is an attractive therapeutic strategy for cancer therapy, molecular determinants for efficacy of PI3K inhibitors (PI3Kis) remain unclear. We previously identified that overexpression of insulin-like growth factor 1 receptor (IGF1R) contributed to the development of drug resistance after long-term exposure to PI3Kis. In this study, we examined the involvement of basal IGF1R expression in intrinsic resistance of drug-naïve cancer cells to PI3Kis and whether inhibition of IGF1R overcomes the resistance. We found that cancer cells highly expressing IGF1R showed resistance to dephosphorylation of Akt and subsequent antitumor effect by ZSTK474 treatment. Knockdown of IGF1R by siRNAs facilitated the dephosphorylation and enhanced the drug efficacy. These cells expressed tyrosine-phosphorylated insulin receptor substrate 1 at high levels, which was dependent on basal IGF1R expression. In these cells, the efficacy of ZSTK474 in vitro and in vivo was improved by its combination with the IGF1R inhibitor OSI-906. Finally, we found a significant correlation between the basal expression level of IGF1R and the inefficacy of ZSTK474 in an in vivo human cancer panel, as well as in vitro. These results suggest that basal IGF1R expression affects intrinsic resistance of cancer cells to ZSTK474, and IGF1R is a promising target to improve the therapeutic efficacy. The current results provide evidence of combination therapy of PI3Kis with IGF1R inhibitors for treating IGF1R-positive human cancers.

Purpose To clarify the efficacy of palliative radiotherapy for the relief of symptoms due to skin invasion in patients with breast cancer. Materials and methods We conducted a multi-institutional prospective observational study of patients who received palliative radiotherapy for skin invasion due to a primary lesion or chest wall recurrence. Bleeding/discharge, offensive odor, pain and QOL scores were evaluated before and 1, 3 and 6 months after radiotherapy. Results Twenty-one patients were assessed. Sixteen patients (76%) received 36 Gy in 12 fractions. The mean (±1 SD) score of bleeding/discharge was 1.90 ± 0.89 before radiotherapy, 1.50 ± 0.74 at 1 month, 0.47 ± 0.58 at 3 months, and 0.82 ± 1.04 at 6 months (P = 0.001). The mean score of offensive odor was 1.21 ± 1.38 before radiotherapy, 0.71 ± 0.92 at 1 month, 0.20 ± 0.41 at 3 months, and 0.27 ± 0.62 at 6 months (P = 0.008). The mean score of pain was 2.90 ± 1.22 before radiotherapy, 3.05 ± 1.36 at 1 month, 3.29 ± 1.10 at 3 months, and 3.31 ± 1.54 at 6 months (P = 0.431). The mean total score of QOL-ACD/QOL-ACD-B was 126.2 ± 24.5 before radiotherapy, 130.3 ± 26.3 at 1 month, 136.2 ± 26.6 at 3 months, and 126.6 ± 32.8 at 6 months (P = 0.178). Conclusion Palliative radiotherapy for skin invasion in patients with breast cancer might be effective, especially for the relief of bleeding/discharge and offensive odor.

Although a few investigators have demonstrated the effect of concurrent chemoradiotherapy (CRT) for postoperative recurrent non-small cell lung cancer (NSCLC), the outcome of this treatment remains unclear. The aim of this study was to elucidate the efficacy and tolerability of concurrent CRT with cisplatin (CDDP) and vinorelbine (VNR) in patients with postoperative locoregional recurrent NSCLC. A total of 40 patients who had received concurrent CRT with CDDP and VNR between January 1999 and December 2014 were retrospectively analyzed. Patients were treated with CDDP (80 mg/m2 on day 1) and VNR (20 mg/m2 on days 1 and 8) every 4 weeks. Radiotherapy was administered concurrently during cycle 1. The delivered x-ray radiation dose was 60 Gy in all 37 patients who received x-ray radiotherapy; 3 patients received proton beam radiation (66 Gy [RBE] in 1 patient and 60 Gy [RBE] in 2 patients). The objective response rate was 85% (95% confidence interval [CI], 70.9%–92.9%). The median progression-free survival was 20.3 months (95% CI, 12.9 months–not reached). The 2-year survival rate was 78.9% (95% CI, 63.0%–89.1%). The most common grade ≥3 toxicity was neutropenia (18%). No grade ≥3 radiation pneumonitis and no treatment-related deaths were observed. Our study revealed that concurrent CRT with CDDP and VNR was active and safe for patients with postoperative locoregional recurrent NSCLC. Salvage CRT for postoperative locoregional recurrent NSCLC might be a promising treatment for selected patients.

Background/aim We assessed the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) in patients with squamous cell carcinoma of the cervical esophagus. Patients and methods We retrospectively analyzed 37 patients treated with definitive CCRT. The patients received radiotherapy at a fraction dose of 2 Gy (total; 60 or 70 Gy) and concurrent chemotherapy. Adjuvant chemotherapy consisted of 1 to 2 cycles of 5-fluorouracil plus cisplatin or nedaplatin. Results The median follow-up was 119.0 months, the 10-year overall survival, progression-free survival and laryngectomy-free survival rates were 35.6, 19.9 and 30.2% respectively. In the univariate analysis, T stage (T4 vs. T1-3) was the only prognostic factor for PFS. The most common acute toxicity was leukocytopenia (Grade 3; 27%). As for late toxicities, 4 patients (11%) developed Grade 2 or 3 esophageal strictures. Conclusion The results of this study demonstrated that CCRT yielded satisfactory clinical outcomes with acceptable toxicities.

Volumetric-modulated arc therapy (VMAT) is a widespread intensity-modulated radiation therapy (IMRT) method, however, VMAT requires adaptation of the radiation treatment planning system (RTPS) and linear accelerator (linac); these upgrades are quite expensive. The Smart Arc of Pinnacle(3) (Philips), which is the software used in VMAT calculations, can select constant dose rate (CDR) mode. This approach has a low initial cost because the linac upgrade is not required. The objective of this study was to clarify the utility of CDR mode for prostate IMRT. Pinnacle(3) and Clinac 21EX linac (Varian, 10 MV X-rays) were used for planning. The plans were created for 28 patients using a fixed multi-field IMRT (f-IMRT), VMAT and CDR techniques. The dose distribution results were classified into three groups: optimal, suboptimal and reject. For the f-IMRT, VMAT and CDR results, 25, 26 and 21 patients were classified as 'optimal', respectively. Our results show a significant reduction in the achievement rate of 'optimal' for a CDR when the bladder volume is100 cm(3). The total numbers of monitoring units (MUs) (average ± 1σ) were 469 ± 53, 357 ± 35 and 365 ± 33; the average optimization times were ∼50 min, 2 h and 2 h 40 min, and the irradiation times were ∼280 s, 60 s and 110 s, respectively. CDR can reduce the total MUs and irradiation time compared with f-IMRT, and CDR has a lower initial cost compared with VMAT. Thus, for institutions that do not currently perform VMAT, CDR is a useful option. Additionally, in the context of patient identification, bladder volume may be useful.

Background Although several studies suggested that immune checkpoint inhibitors may enhance an efficacy of radiotherapy (RT), it remains unclear in patients (pts) with advanced gastric cancer (AGC). Methods Total 34 AGC pts treated with RT for the primary gastric lesion from April 2013 to March 2019 were analyzed in this study. Pts were divided into two groups according to whether they had received nivolumab before RT or not. Primary tumor responses were assessed according to volumetry on CT scan with tumor response as > 70% decrease in tumor volume. Endoscopic responses were evaluated in pts who underwent endoscopy after RT. Tumor infiltrating lymphocytes (TILs) were also analyzed to examine the tumor microenvironmental immune status in the pts. Results Among 34 pts, 16 pts had received nivolumab before RT. There were no significant differences in baseline characteristics between nivolumab-exposed and nivolumab-naive groups. 70% tumor reductions by RT were observed in 25% (4/16) in nivolumab-exposed group but no patients (0/18) in nivolumab-naive group (P = 0.039). Among pts who received endoscopy after RT, four of seven pts in nivolumab-exposed group experienced partial response, while no response was observed among 10 nivolumab-naive pts (P = 0.015). TILs were evaluated in pts whose tumor samples were available. CD8+ T cells/effector regulatory T cells (eTreg cells) ratio in TILs was markedly increased after nivolumab in pts who achieved response, but not observed in pts who had no tumor reduction. A significant increase of CD8+ T cells/eTreg cells ratio after nivolumab treatment was observed in nivolumab-exposed pts (n = 15), whereas such a tendency was not observed in nivolumab-naive pts (n = 10). Conclusions RT to primary gastric cancer significantly led to tumor response in nivolumab-exposed pts compared with nivolumab-naive pts. Immune profiling suggested that nivolumab might enhance the sensitivity to RT by immunoactivation via increasing CD8+ T cell/eTreg cell ratio.

Purpose This study aims to clarify the time-course of gas accumulation in the rectum during treatment as guidance for the management of rectal volumes. Materials and Methods We reviewed 2042 sets (35.2 sets per patient) of anteroposterior and right–left mega voltage (MV) images obtained for daily set-up from 58 patients who underwent radical external beam radiotherapy for localised prostate cancer. The patients were instructed to take magnesium oxide tablets during radiotherapy. They were also encouraged to avoid foods that might cause intestinal gas during radiotherapy. Gas accumulation in the rectum was graded into three classes by the same radiation oncologist. If no gas was seen in the rectum, it was classified as grade 0. A small amount of gas was classified as grade 1, whereas a marked amount of gas that required removal was classified as grade 2. Results Of the 2042 sets of MV images, grades 1 and 2 gas accumulation were seen in 332 (16%) and 156 (8%), respectively. By the trend test, gas accumulation significantly decreased towards the end of treatment (P = 0.02 for grade 1 or 2 and P = 0.02 for grade 2). On multivariate analysis, we did not identify any significant independent predictors for either baseline gas accumulation or gas reduction. Conclusion Gas accumulation tended to decrease until the end of treatment. This tendency should be reconfirmed by other institutions.

Objective To assess the feasibility of proton beam therapy for the patients with locally advanced non-small lung cancer. Methods The dosimetry was analyzed retrospectively to calculate the doses to organs at risk, such as the lung, heart, esophagus and spinal cord. A dosimetric comparison between proton beam therapy and dummy photon radiotherapy (three-dimensional conformal radiotherapy) plans was performed. Dummy intensity-modulated radiotherapy plans were also generated for the patients for whom curative three-dimensional conformal radiotherapy plans could not be generated. Results Overall, 33 patients with stage III non-small cell lung cancer were treated with proton beam therapy between December 2011 and August 2014. The median age of the eligible patients was 67 years (range: 44-87 years). All the patients were treated with chemotherapy consisting of cisplatin/vinorelbine or carboplatin. The median prescribed dose was 60 GyE (range: 60-66 GyE). The mean normal lung V20 GyE was 23.6% (range: 14.9-32%), and the mean normal lung dose was 11.9 GyE (range: 6.0-19 GyE). The mean esophageal V50 GyE was 25.5% (range: 0.01-63.6%), the mean heart V40 GyE was 13.4% (range: 1.4-29.3%) and the mean maximum spinal cord dose was 40.7 GyE (range: 22.9-48 GyE). Based on dummy three-dimensional conformal radiotherapy planning, 12 patients were regarded as not being suitable for radical thoracic three-dimensional conformal radiotherapy. All the dose parameters of proton beam therapy, except for the esophageal dose, were lower than those for the dummy three-dimensional conformal radiotherapy plans. In comparison to the intensity-modulated radiotherapy plan, proton beam therapy also achieved dose reduction in the normal lung. None of the patients experienced grade 4 or worse non-hematological toxicities. Conclusions Proton beam therapy for patients with stage III non-small cell lung cancer was feasible and was superior to three-dimensional conformal radiotherapy for several dosimetric parameters.

Summary Objective The aim of this study was to describe a case series of three simultaneous cases of spontaneous pneumomediastinum (SPM) with epidural pneumatosis during vocal training. Methods A report of three cases with chart review was performed. Literature review was carried out using PubMed. Results This was an extremely rare case series where at least three of the 20 participants of a vocal training in a self-development seminar developed SPM, epidural pneumatosis, pneumothorax, and subcutaneous emphysema. All cases improved with bed rest. Simultaneous cases of SPM have been reported in the past. However, the cause of simultaneous occurrence has not been explained clearly. In our cases, continuous excessive vocal training may have caused intrathoracic pressure to rise, causing SPM at a high prevalence. Epidural pneumatosis is a rare finding. Studies on epidural pneumatosis complicating SPM are limited. Air is said to easily pass through the cervical region owing to the close proximity between the mediastinum and the upper spine, resulting in epidural pneumatosis. Elevated intrathoracic pressure while the glottis is closed may worsen the risk for epidural pneumatosis. In this seminar, continuous effortful vocal training at full pitch with few pauses for breath may have contributed to this simultaneous occurrence. Conclusions We report three simultaneous cases of SPM and epidural pneumatosis due to demanding vocal training. Further research on this subject is desired to identify risk factors.

In this paper, we suggest a new method for verifying the motion of a binary multileaf collimator (MLC) in helical tomotherapy. For this we used a combination of a cylindrical scintillator and a general-purpose camcorder. The camcorder records the light from the scintillator following photon irradiation, which we use to track the motion of the binary MLC. The purpose of this study is to demonstrate the feasibility of this method as a binary MLC quality assurance (QA) tool. First, the verification was performed using a simple binary MLC pattern with a constant leaf open time; secondly, verification using the binary MLC pattern used in a clinical setting was also performed. Sinograms of simple binary MLC patterns, in which leaves that were open were detected as "open" from the measured light, define the sensitivity which, in this case, was 1.000. On the other hand, the specificity, which gives the fraction of closed leaves detected as "closed", was 0.919. The leaf open error identified by our method was -1.3 +/- 7.5%. The 68.6% of observed leaves were performed within +/- 3% relative error. The leaf open error was expressed by the relative errors calculated on the sinogram. In the clinical binary MLC pattern, the sensitivity and specificity were 0.994 and 0.997, respectively. The measurement could be performed with -3.4 +/- 8.0% leaf open error. The 77.5% of observed leaves were performed within +/- 3% relative error. With this method, we can easily verify the motion of the binary MLC, and the measurement unit developed was found to be an effective QA tool., Article, JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS. 13(1):27-43 (2012)

BACKGROUND The purpose of this study was to compare the prevalence of treatment techniques including intensity-modulated radiation therapy and image-guided radiation therapy in external-beam radiation therapy for prostate cancer in Japan. METHODS A national survey on the current status of external-beam radiation therapy for prostate cancer was performed in 2010. We sent questionnaires to 139 major radiotherapy facilities in Japan, of which 115 (82.7%) were returned. RESULTS Intensity-modulated radiation therapy was conducted at 67 facilities (58.3%), while image-guided radiation therapy was conducted at 70 facilities (60.9%). Simulations and treatments were performed in the supine position at most facilities. In two-thirds of the facilities, a filling bladder was requested. Approximately 80% of the facilities inserted a tube or encouraged defecation when the rectum was dilated. Some kind of fixation method was used at 102 facilities (88.7%). Magnetic resonance imaging was routinely performed for treatment planning at 32 facilities (27.8%). The median total dose was 76 Gy with intensity-modulated radiation therapy and 70 Gy with three-dimensional radiation therapy. The doses were prescribed at the isocenter at the facilities that conducted three-dimensional radiation therapy. In contrast, the dose prescription varied at the facilities that conducted intensity-modulated radiation therapy. Of the 70 facilities that could perform image-guided radiation therapy, 33 (47.1%) conducted bone matching, 28 (40.0%) conducted prostate matching and 9 (12.9%) used metal markers. Prostate or metal marker matching tended to produce a smaller margin than bone matching. CONCLUSIONS The results of the survey identified current patterns in the treatment planning and delivery processes of external-beam radiation therapy for prostate cancer in Japan.

To evaluate variation in bladder volume of full bladders in definitive radiotherapy for localized prostate cancer and to investigate potential predictors of increased bladder volume variations. In 40 patients, the bladder volume was measured with megavoltage computed tomography (MVCT) imaging performed just before irradiation during the administration of the 1st fraction (#1), the 10th fraction (#10), the 20th fraction (#20), and the 30th fraction (#30). Patients were instructed to avoid urinating for 60–90 minutes before the planning CT (pln-CT) scan and before daily irradiation. Patients were also encouraged to drink an unspecified volume of liquid that would result in a clear but tolerable urge to urinate. The population-mean bladder volume (±1SD) was 219 ml (±83 ml) at the planning CT scan (pln-CT), 186 ml (±96 ml) at #1, 149 ml (±73 ml) at #10, 137 ml (±59 ml) at #20, and 136 ml (±60 ml) at #30. The mean intrapatient variation in bladder volume (1 SD relative to the mean bladder volume of each patient) was 38% (range: 10–84%). The bladder volume at the pln-CT was correlated with the intrapatient variance in bladder volume with a correlation coefficient of 0.54 and p

The locoregional recurrence of breast cancer is not a sign of distant metastases, and a substantial proportion of cases are cured by salvage therapy. Patients with locoregional recurrence should not be treated with palliative intent as if they have visceral metastases. The recommended treatment for ipsilateral breast recurrence after breast conservative therapy is a mastectomy. For patients who suffer from isolated chest wall recurrence after mastectomy, a surgical approach is recommended. Neoadjuvant chemotherapy is considered for patients with unresectable disease in order to render the disease resectable. For patients with isolated chest wall recurrence who have received no prior radiotherapy, postoperative radiotherapy involving the chest wall and regional lymph nodes is recommended. Patients with isolated axillary lymph node recurrence should be treated with axillary dissection or resection. Although the effectiveness of systemic therapy for patients with locoregional recurrence is unclear, there is a trend toward treating patients with supraclavicular lymph node recurrence with radiotherapy plus systemic therapy. Pain relief and the eradication of other distressing symptoms resulting from inoperable disease are achieved in two-thirds to three-quarters of patients by radiotherapy with or without systemic therapy. New anti-cancer agents and molecular target therapies should be evaluated with the objective of improving the treatment outcome of patients with locoregional recurrence. A combination of approaches is required for treatment of patients with locoregional recurrence, and a multidisciplinary tumor board should be organized at each institute.

Objective To evaluate Japanese tolerability to pilocarpine of 5 mg t.i.d. Methods From January 2006 to July 2006, 39 patients with xerostomia received 5 mg t.i.d. pilocarpine for at least for 12 weeks unless they had experienced unacceptable adverse effects. All patients received radiotherapy that included the parotid glands in the radiation field >50 Gy. The body weights of the patients ranged from 42 to 73 kg (median 60 kg). Results Thirty-six of the 39 patients were evaluable. The tolerated rate was only 47%. Of the 25 patients whose body weights were less than 65 kg, the tolerated rate was 36%, whereas the rate of the 11 patients whose body weights were 65 kg or above was 72% (p = 0.050). The most common adverse effect was sweating with an incidence of 64%. Response rate, which was defined as the total number of patients with an increase of at least 25 mm from the baseline in the VAS score divided by the number of maintaining patients among those who started pilocarpine after more than 4 months from the start of radiotherapy, was 40% at 12 weeks (n = 15). Conclusion For Japanese, 5 mg t.i.d. pilocarpine caused a high incidence of unacceptable adverse effects. A lower dose of pilocarpine needs to be considered.

Aim: This study was conducted to evaluate the effect of external radiation therapy on lymph node metastases from hepatocellular carcinoma (HCC). Methods: A total 28 patients with cytopathologically proven HCC were subjected to radiation therapy over a 5-year period, and treatment was continued in all cases. All patients underwent irradiation with a total dose ranging between 46 and 60 Gy in daily 2.0-Gy fractions, five times a week. Results: Among the metastatic lesions treated, 18 (64%) and five (18%) patients achieved partial responses and complete responses, respectively. The 1- and 2-year overall survival rates and the median survival time were 53% and 33%, respectively, and 13 months in patients given external beam radiation therapy (EBRT) for a non-palliative, near-cure intent (n = 21). Conclusions: Although lymph node metastasis from HCC is sensitive to EBRT, the intent of EBRT should be limited to palliation. For palliative purposes, it is useful in treatment with 50 Gy in 25 fractions for these patients.

This multicenter prospective study ( Japanese Radiation Oncology Study Group: JROSG 05-5) aimed to evaluate the effectiveness of postoperative radiotherapy (PORT) in patients with ductal carcinoma in situ (DCIS) with an involved surgical margin or close margin widths of ≤1 mm or less. PORT consisted of whole-breast irradiation (50 Gy in 25 fractions) followed by boost irradiation (10 Gy in 5 fractions). Eligibility criteria were as follows: (i) DCIS without an invasive carcinoma component, (ii) age between 20 and 80 years old, (iii) involved margin or close margin widths of ≤1 mm, (iv) refusal of re-resection, (v) performance status of 0–2, and (vi) written informed consent. The primary endpoint was ipsilateral breast tumor recurrence (IBTR), and secondary endpoints were overall survival (OS), relapse-free survival (RFS), recurrence patterns, and adverse events. A total of 37 patients from 12 institutions were enrolled from January 2007 to May 2009. The median follow-up time was 62 months (range, 28–85 months). The median pathological tumor size was 2.5 cm (range, 0.3–8.5 cm). Of the 37 patients, 21 had involved margins, and 16 had close margins. The 5-year IBTR, OS and RFS rates were 6% (95% confidence interval [CI]: 2–21), 97% (95% CI: 83–99) and 91% (95% CI: 77–97), respectively. Two patients developed local recurrence at the original site after 39 and 58 months. No severe adverse events were found. Our study suggests that this PORT regimen could be a treatment option for patients with DCIS with involved margin or close margin who don't desire re-resection.

Purpose: To analyze the outcomes of patients with early hypopharyngeal cancer treated with radical radiotherapy (RT). Methods and Materials: Ten institutions combined the data from 115 patients with Stage I–II hypopharyngeal squamous cell carcinoma treated with definitive RT between 1990 and 2001. The median patient age was 67 years; 99 patients were men and 16 were women. Of the 115 patients, 39 had Stage I and 76 had Stage II disease. Conventional fractionation was used in 98 patients and twice-daily RT in 17 patients; chemotherapy was combined with RT in 57 patients. The median follow-up period was 47 months. Results: The overall and disease-specific 5-year survival rate for 95 patients without synchronous malignancies was 66.0% and 77.4%, respectively. The 5-year disease-specific survival rate by T stage was 95.8% for patients with T1 disease and 70.1% for patients with T2 disease ( p = 0.02). Of the 115 patients, local control with laryngeal voice preservation was achieved in 34 of 39 patients with T1 lesions, including 7 patients successfully salvaged, and in 56 of 76 patients with T2 lesions. Sixty-five patients (56.5%) had synchronous or metachronous cancers. Of the 115 patients, 19 died of hypopharyngeal cancer, 10 died of second primary cancers, and 14 died of other causes during the study and follow-up periods. Conclusions: Patients with early hypopharyngeal cancer tended to have a good prognosis after RT. However, second malignancies had an adverse effect on the overall outcomes of patients with early hypopharyngeal cancer.

In this study we analyzed our cases of localized aggressive lymphoma treated in our institution during the last 20 years to compare the finding of this study with those of previous studies. Forty patients with Ann Arbor stage I-II aggressive lymphoma were treated with 3-6 cycles of a CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisolone) and radiation therapy (30 or 40 Gy with involved field). Between 1985 and 2003, 40 patients with stage I (N = 25) or stage II (N = 15) disease were treated. Chemotherapy mainly preceded radiotherapy, although the sequence of radiotherapy and chemotherapy was determined by individual physicians and patients' choice. Median and mean age was 50.5 and 48.6 years, respectively, at the time of diagnosis, with a male to female ratio of 19:21. Analyses were undertaken to determine (1) response to treatment according to age, international prognostic index (IPI), lactate dehydrogenase (LDH) value, serum interleukin 2 receptor (sIL-2R) value, cell type, stage, extent of maximum local disease, with or without mediastinal lymph nodes, number of sites, anatomic distribution, and irradiation dose, and (2) relapse patterns. Complete follow-up was obtained in all patients. The follow-up period of surviving 33 patients ranged from 24.7 to 180 months with a median of 69 and a mean of 72.7 months. A complete remission (CR) was achieved in 37 patients (93%). A study of relapse patterns after a CR showed that four patients had a first relapse within a radiation field and the other one patient had an extranodal distant relapse. Significant prognostic factors were not identified by multivariate analysis. Combined chemotherapy and radiation therapy is safe, highly effective, and probably curative for most patients with stage I-II aggressive lymphoma.

Aim: We describe the clinical presentation, evaluation, management and outcome of patients experiencing small bowel perforation following radiation therapy for cervical cancer. Methods and Materials: A database consisting of 95 Japanese women with stage 0–4 A cervix cancer treated between 1991 and 2004 contained seven patients (7.4%) with small bowel perforation. Results: The median age at the time of perforation was 72.5 years (range 62–78). The median time from completion of radiotherapy to perforation was 6 months (range 2–58). Surgery (one small bowel resection and anastomosis with diversion; six small bowel resection and anastomosis) was performed immediately in all seven patients. One of seven patients died of small bowel perforation (i.e. mortality rate was 14%). Bowel adhesion was detected during the operation in only three cases (43%). Signs of peritonitis were absent in six cases (86%). Severe abdominal pain was seen in all seven patients. The perforation site was ileum in all seven cases. In all patients, pathological changes were compatible with postirradiation injury of the gastrointestinal tract. Conclusions: The presenting complaints of patients with bowel perforation following radiotherapy vary, and signs of peritonitis may be absent. Emergency physicians must be alert for these complications in patients who have been treated with radiotherapy.

Intensity-modulated radiation therapy (IMRT) allows greater dose conformity to the tumor target. However, IMRT, especially static delivery, usually requires more time to deliver a dose fraction than conventional external beam radiotherapy (EBRT). The authors have been using a “two-axis dynamic arc therapy” (2A-DAT) technique for prostate cancer treatment to make a concave dose distribution to spare the rectum and bladder while working with limited time and human resources. The objectives of this study were to (1) clinically implement the 2A-DAT technique, (2) evaluate the dosimetry in comparison with IMRT, and (3) analyze the initial treatment outcome. The 2A-DAT consists of two dynamic arc therapies (DATs) with half rotation around two isocenters each in two separate symmetrical rhombi. Treatment planning is forward and on a trial-and-error basis. Thirty-four patients received 2A-DAT with a median prescribed dose of 70 Gy. Although inferior in dose uniformity, the 2A-DAT provided equivalent sparing of normal structures to IMRT. Daily fraction delivery time for the 34 patients ranged from 6.4 to 9.6 minutes, with an average of 7.4 minutes. Five-year survival and five-year prostate specific autigen (PSA) failure-free survival were 89.3% and 79.5%, respectively. Three patients developed grade 2 procitis. This technique is a possible alternative to IMRT in EBRT of prostate cancer

To evaluate the treatment outcome of preoperative neoadjuvant radiotherapy combined with chemotherapy (CTx) for 17 esophageal cancer patients. Between 1992 and 2004, patients with locally advanced esophageal cancer (stage III or IV) before curative-intent surgery received radiotherapy (RT) combined with CTx (Cisplatin: 75 mg/m2, bolus infusion, and 5-fluorouracil (5-FU): 1,000 mg/m2/24 h, continuous infusion for 4 days) at a median total dose of 30 Gy (n=17). The median survival period was 13.8 months. The overall survival rates at 1, 2, and 3 years were 75%, 40%, and 20%, respectively. According to univariate analysis, no factor of worse prognosis was found. Pathological markedly (Grade 3) or moderately (Grade 2) effects were observed in 4 patients (24%) and 8 patients (47%), respectively. These results indicate that, although this regimen was effective in terms of pathological effect, it is unclear whether it made a contribution to the improvement of survival rate.

Purpose: To evaluate the treatment outcome of concurrent chemoradiation therapy (cCRT) for 13 clinically confirmed T1 esophageal cancer patients. Methods: Between June 2000 and February 2004, patients with T1 esophageal cancer (tumor invading lamina propria or submucosa) received cCRT (50.4 Gy; CDDP: 75 mg/m2, day 1, bolus; 5-FU: 1000 mg/m2, days 1 to 4, continuous) (n = 13, T1 group). This treatment regimen was compared with the following 2 other groups treated during the same period: one was treated with radiation therapy alone for T1 disease (n = 5, RT-alone group); and the other group of patients consisted of those with T2 disease (tumor invading muscularis propria) who received the same cCRT regimen as the first T1 group (n = 9, T2 group). Results: The overall survival rates at 1 and 3 years were in the T1 group, 75% and 75%; in the T2 group, 75% and 45% (P =0.2890); and in the RT-alone group, 60% and 40% (P = 0.2978). No treatment-related mortalities occurred in the T1 and RT-alone groups, but one patient in the T2 group died of radiation-induced pneumonitis. Conclusions: Although this study was not randomized, the results showed that cCRT is a safe and effective method for treating patients with superficial esophageal cancer.