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Background and purpose Intensity-modulated radiation therapy (IMRT) is increasingly applied in concurrent chemoradiotherapy (CCRT) for locally-advanced non-small cell lung cancer (NSCLC), with improvement of target coverage and better sparing of normal tissue. IMRT tends to have a larger low-dose irradiation volume than 3D conformal radiotherapy, but the incidence of and risk factors for pneumonitis remain unclear, especially following the approval of durvalumab. Materials and methods We retrospectively reviewed the records of NSCLC patients treated by CCRT using IMRT at seven Japanese institutions. Primary outcomes were incidence of symptomatic pneumonitis and progression-free survival (PFS). Multivariate logistic regression analysis was used to identify risk factors for ≥grade 2 pneumonitis. Results Median follow-up from the start of CCRT was 14.3 months (n = 107 patients; median age 70 years, 29% female). Median lung V5 and V20 was 49.2% and 19.5%, respectively. Durvalumab was administered to 87 patients (81%). Pneumonitis developed in 95 (89%) patients of which 53% had grade 1, 28% grade 2, 6.5% grade 3, and 0.9% grade 4. Durvalumab had been discontinued in 16 patients (18.4%) due to pneumonitis. By multivariate analysis, age ≥70 years, male sex, and V5 ≥58.9% were identified as significantly associated with ≥grade 2 pneumonitis (p = 0.0065, 0.036 and 0.0013 respectively). The median PFS from the start of CCRT was not reached (95% CI, 14.2 months to not reached) in patients receiving durvalumab. Conclusion CCRT using IMRT followed by durvalumab was generally effective and tolerable; V5

After the second war, Wilson who participated in development of the atomic bomb in Los Alamos studied peaceful use of atomic energy and proposed a property of proton beam that has potential to treat cancer. According to his proposal, the first patient was treated with proton beam therapy at the University of California Berkley in 1954. The first series of proton beam therapy for patients with esophageal cancer was reported from Japan in 1993. After that many proton facilities in Japan reported the clinical outcome of patients with esophageal cancer. Many dosimetric and clinical studies showed proton beam therapy for esophageal cancer was less toxic than photon beam therapy, however there is a paucity of randomized trials and evidence that proton beam therapy has clearly superior survival compared to photon therapy. Only one randomized trial has been conducted to study less toxicity for proton beam compared with intensity modulated radiotherapy (IMRT), which was stopped early because toxicities of IMRT were higher. A phase III study comparing overall survival between proton beam therapy and IMRT is now activated. A cost reduction for proton therapy is necessary to facilitate patient care and establishment of clinical evidence.

Definitive chemoradiation (dCRT) is the mainstay treatment for cStage IVa esophageal squamous cell carcinoma (ESCC) with good performance status (PS), according to standard practice guidelines. Salvage surgery may incur operation complications and risk of mortality. According to the esophageal cancer practice guidelines outlined by the Japan Esophageal Society, when a tumor is residual and recurrent, chemotherapy and palliative symptomatic treatment is continued. However, salvage operation has been selected as a therapeutic option for recurrent or residual tumors after dCRT. There is weak evidence for not recommending surgery for cStage IVa ESCC exhibiting residual disease following dCRT. It has been reported that during salvage surgery the only prognostic factor that is thought to be performed is complete resection (R0), but at the same time, salvage esophagectomy increases the incidence of postoperative complications and mortality. The phase II chemoselection study by Yokota T et al. in Japan showed that multidisciplinary treatment initiated by induction therapy, in which docetaxel is added to cisplatin and 5-fluorouracil, resulted in a good prognosis in the short term. In this review, we discuss the surgical strategy and future of unresectable clinical T4 (cT4) ESCC.

Carbon 11-choline positron emission tomography/computed tomography (11C-choline PET/CT) and subsequent local therapy for oligometastatic prostate cancer have been reported to be effective, but their effectiveness in castration-resistant prostate cancer (CRPC) remains unclear. Here, we evaluated the findings of 11C-choline PET/CT in CRPC patients and the efficacy of local treatments in correspondence of the pathologic choline uptake. We collected 12 cases of CRPC patients who underwent 11C-choline PET/CT between 2014 and 2016. The outcomes assessed included age, the prostate-specific antigen (PSA) value, the findings of 11C-choline PET/CT, the subsequent treatments, the PSA response following the treatments, and the progression-free survival (PFS). Seven of 12 cases (median PSA, 3.29 ng/mL) had local prostate cancer and/or one or two metastatic lesions detected by the choline PET/CT. These localized lesions were treated with radiotherapy or lymphadenectomy. PSA decreased in all the seven cases and median PSA response was 86% (range, 23–100%). Median PFS was 8.5 months (range, 2.8–25.3 months). The other five cases (median PSA, 7.41 ng/mL) had multiple metastases and systemic therapies were continued in those cases. 11C-choline PET/CT and the correspondent local treatments may play an important role in the treatment sequence of CRPC in selected patients.

We conducted a Phase II study to evaluate the usefulness of compensator-based non-coplanar intensity-modulated radiotherapy (ncIMRT) for patients with surgically inaccessible Stage I non–small-cell lung cancer (NSCLC). Patients with pathologically proven or clinically diagnosed surgically inaccessible Stage I NSCLC were enrolled in this study from May 2011 to April 2014. These patients underwent ncIMRT of 75 Gy in 30 fractions regardless of the tumor location. The primary end point was 3-year overall survival, and the secondary end points were local control rate and treatment-related toxicities. A total of 48 patients (50 tumors) were enrolled in this study. Of the 50 tumors, the Stage T1 to T2 ratio was 31 to 19, and the ratio of tumors located in the central to peripheral areas was 11 to 39. During the median follow-up time of 35.9 months, the 3-year actuarial local progression-free and overall survival rates were 82.6% and 87.1%, respectively. No patients experienced toxicities of Grade 3 or greater. Standard-fractionated ncIMRT was effective and safe for patients with surgically inaccessible stage I NSCLC, regardless of the tumor location.

Quantitative CT assessment of patients with pulmonary emphysema is used to measure pulmonary function. The present study evaluated whether the quantitative CT value can accurately estimate the risk of radiation pneumonitis (RP) after stereotactic body radiotherapy (SBRT) for non-small cell lung cancer (NSCLC) in patients with and without emphysema. A total of 80 patients with stage I NSCLC receiving SBRT at a dose of 50 or 60 Gy in five fractions at our hospital between November 2003 and October 2015 were included in the analysis. A total of 33 (41%) patients were diagnosed with emphysema on CT examination. Dosimetric parameters, quantitative CT percentage value of low attenuation area (LAA%) in the whole lung, and average whole lung CT density values were used to examine the risk of RP. Among the 80 patients, 26 (33%) and 3 (4%) experienced Grade 1 and Grade 2 RP, respectively, during the median observation period of 18.8 (1.8-106.8) months. The RP rate for patients with a LAA% (25% (P=0.037). The RP rate in subjects with an average HU value of >-790 HU was significantly higher compared with that of patients with ≤-790 HU (P=0.036). Age (hazard ratio [HR]=2.46; P=0.03) and average HU (HR=3.39; P=0.02) were significantly associated with RP, whereas mean lung dose was not identified to be significant in multivariate analysis. The quantitative CT value was associated with RP after SBRT.

The aim of this study is to clarify changes in the circumstances of cancer diagnoses during the COVID-19 pandemic in Tokyo, Japan, estimated from [(18)F]-2-fluoro-2-deoxy-D-glucose (FDG) -positron emission tomography/ computed tomography (PET/CT) for cancer patients. Cancer diagnosis in pandemic status (PANS) was evaluated by retrospective review of the findings of FDG-PET/CT examinations performed between 11 March 2020 and 28 December 2021 for initial staging and restaging for malignancy. Evaluation of cancer diagnosis in pre-pandemic status (pPANS) was conducted similarly in FDG-PET/CT examinations performed between 4 January 2018 and 10 March 2020. Of these, patients with malignant lymphoma (ML), lung cancer, esophageal cancer, and colorectal cancer who had a pathologically proven diagnosis or clinical diagnosis following therapy of the disease were selected for analysis. Initial cancer staging was determined by the diagnostic report of FDG-PET/CT. Change in cancer stage and in the number of FDG-PET/CT examinations performed was evaluated between pPANS and PANS, and according to term of the pandemic and vaccination status. The COVID-19 epidemic influenced the number of cancer patients who underwent FDG-PET/CT. There was a marked decrease in the number of cancer patients receiving FDG-PET/CT in Terms 1-3 (March 2020 to February 2021), but it recovered in Terms 4-6 (March 2021 to December 2021). There was no significant difference between PANS and pPANS in terms of the initial stage of cancer, but Stage IV ML and Stage II esophageal cancer were more frequent in PANS. Initial staging of ML, lung cancer, and esophageal cancer revealed more advanced cancer stages in Terms 4-6 compared with Terms 1-3. The number of patients receiving FDG-PET/CT in Tokyo was influenced by the COVID-19 epidemic. Staging based on FDG-PET/CT shifted to more advanced cancer stage during the pandemic compared with pre-pandemic.

Purpose The purpose of this research is to clarify the effects of low monitor unit (MU) on multileaf collimator (MLC) position accuracy and dose distribution in intensity modulated radiotherapy (IMRT) using respiratory gated. Method In the phantom experiment, irradiation without respiratory gated and respiratory gated with low MU (3, 5, and 7 MU) were performed, and positional accuracy and dose distribution of MLC were analyzed. MLC positional accuracy was calculated from the log-files and the MLC position error, gap size error, MLC leaf speed were calculated and compared with the planned value. Gamma analysis of the dose distribution obtained from the irradiated films and the dose distribution of the treatment plans were carried out. Results Without respiratory gated and respiratory gated, the frequency of gap size error that did not exceed 0.2 mm were more than 93% under all conditions. MLC position error increased with increasing MLC leaf speed. The determination coefficient of respiratory gated irradiation was lower by about 20% compared with that without respiratory gated, and variation from the approximate straight line occurs. The output difference due to low MU irradiation during respiratory gated was within 1% of the planned value. Although, the pass rate of gamma analysis differed in tumor size, the dose distribution well conformity at 96% or more for both without respiratory gated and respiratory gated. However, in the comparison of the profile in the MLC movement direction, respiratory gated irradiation at 3 MU showed a difference of about 9% at the edge of the irradiated field and about 6% at the point where the dose rapidly changed. Conclusion It was shown that MLC position accuracy due to stop and go of MLC leaf can be secured even with low MU irradiation of about 3 MU. However, attention should be paid to the dose of risk organs adjacent to the tumor margin.

Respiratory gated VMAT (volumetric modulated arc therapy) repeats rapid stop and go operations of a MLC (multileaf collimator) by turning the beam on and off by respiratory gating. The rapid stop and go operations of the MLC during respiratory gated irradiation may induce position error of the MLC and may affect output error and dose distribution. The purpose of this study was to clarify the relationship between the MLC position accuracy of the respiratory gated VMAT and the VMAT parameters. In the method, 1 arc, 2 arcs, and 4 arcs plan were created for the virtual target and irradiation was performed without the gated respiration and with the gated respiration. The respiratory gated system used a RPM (real-time position management system). The MLC position error, gap size error, and the MLC leaf speed were calculated from a log-file. In the histogram of the gap size error, the frequency of falling within the error range up to 0.2 mm was about 12 percentage points higher for the gated respiration. The MLC position error increased with increasing the MLC leaf speed. The correlation coefficient between the MLC leaf speed and the MLC position error exceeded 0.96, showing a strong correlation. Dose rate of VMAT parameters decreased with increasing arc number with the gated respiration and without the gated respiration. Gated irradiation was temporarily stopped, and it decreased by about 27% with respect to the dose rate without the gated respiration. The gantry rotation speed repeated the stop and re-rotation operations when gated irradiation was performed. For all arcs, the rotation speed decreased by about 30% compared with the rotation speed without the gated respiration. The pass rate of gamma analysis for each arc plan was about 95%. No effect on gated irradiation dose distribution was observed. Respiratory gated irradiation reduced dose rate change and gantry rotation speed of the VMAT. Reduction of the MLC leaf speed occurred, and the MLC position error and gap size error decreased. The MLC positional accuracy was secured, and it was confirmed that there was no effect on dose distribution by the respiratory gated VMAT.

The association between rectal bleeding and the received dose relative to the volume of the rectum is well established in prostate cancer patients who have undergone radiotherapy. The relative volume of the rectum is affected by the rectal anatomical volume, which depends on the definition of rectal length. Compared with the relative rectal volume, the absolute volume of the rectum may be more associated with rectal bleeding. The present study investigated the absolute volume of the rectum that may be used to predict late rectal bleeding following intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT). The cases of 82 patients of prostate cancer, who underwent IMRT and IGRT, were retrospectively evaluated by evaluating dose volume histograms. The median patient age was 73.4 years (range, 51.3–85.9 years). The median total prescribed dose was 76 Gy given in 38 fractions. The absolute and relative dose volumes of the rectum were evaluated by multivariate analysis, and the optimal dose to prevent rectal bleeding was determined. The actuarial ≥grade 1 rectal bleeding rate at 4 years was 4.5% (95% confidence interval, 1.5–13.4%) with a median observation period of 45.3 months. The absolute rectal volume (ml) treated with 60 Gy was the only significant risk factor for rectal bleeding (P

OBJECTIVE: To investigate whether patients with emphysema, as evaluated by quantitative CT image measurement, are at risk of developing radiation pneumonitis (RP) after radiotherapy (RT) for non-small cell lung cancer (NSCLC). METHODS: Between March 2011 and June 2015, 68 consecutive patients with Stage I NSCLC treated with a RT dose of 75 Gy given in 30 fractions were enrolled. The median age was 79 years and there were 45 males and 23 females. The number of patients with T(1) and T(2) were 49 and 19, respectively. The severity of emphysema was evaluated by the percentages of the low attenuation area (LAA) of ≤−860 or −950 Hounsfield unit (HU) and average HU in the whole lung. RESULTS: The mean difference percentages of LAA of ≤−860 (p = 0.0004) or −950 HU (p = 0.005) and average HU (p = 0.001) in patients with RP were significantly lower than those in patients without RP. The area under curve (AUC) of average HU was significantly higher than AUC of LAA of ≤−860 (p < 0.0001) or −950 HU (p < 0.0001). The RP rate after RT was significantly lower when the average HU values were ≤−850 HU (p = 0.0003). CONCLUSION: Patients with emphysema evaluated by average HU (≤–850 HU) in the whole lung were found to be at low risk of RP after RT. ADVANCES IN KNOWLEDGE: Quantitative measurement of average HU from CT images was predicted of RP after RT.

The aim of the present study was to establish whether intensity-modulated radiotherapy (IMRT) with concurrent gemcitabine and S-1 is a feasible treatment option for patients with locally advanced pancreatic ductal adenocarcinoma. Patients with pancreatic ductal adenocarcinoma were prospectively enrolled. An IMRT dose of 50.4 Gy in 28 fractions with concurrent gemcitabine at a dose of 600 mg/m2 and S-1 at a dose of 60 mg were administrated. Adverse events and associated dosimetric factors were assessed. Between February 2012 and January 2014, 17 patients with borderline resectable and 4 with unresectable pancreatic cancer were enrolled. None of the patients experienced grade 3 or worse nausea and vomiting. The planning target volume (≥200 vs.

The purpose of this study was to evaluate the effectiveness of CT assist for intraarterial chemotherapy in relation to the therapeutic outcomes of intraarterial chemoradiation for advanced head and neck cancer with extension across the anatomical midline (EAM).This retrospective study evaluated 64 consecutive patients. In total, 26 and 38 patients had cancer with or without EAM, respectively. These patients underwent an intraarterial cisplatin infusion (200 mg/m(2), days 1 and 35) and intravenous 5-FU infusion (800 mg/m(2), days 1-5 and 36-39) concomitantly with radiotherapy. Angiography-assisted CT was performed to confirm complete coverage during the intraarterial chemotherapy. The accuracy of diagnosing tumor vessels by digital subtraction angiography (DSA) was evaluated using receiver-operating characteristic analysis by two radiologists. The overall survival and locoregional control rates were calculated by the Kaplan-Meier method.DSA was not useful for diagnosing tumor vessels. The 2-year overall survival rates for the patients with cancer with or without EAM were 83 and 90 %, while the 2-year locoregional control rates were 95 and 82 %, respectively. Locoregional control or the overall survival rates showed no significant differences.Intraarterial chemotherapy using angiography-assisted CT during chemoradiation therapy can achieve comparable therapeutic outcomes for cancer with and without EAM.

The present study was conducted to retrospectively evaluate survival and local control with definitive brachytherapy in patients with cutaneous angiosarcoma of the scalp and/or face, and to determine the optimal radiation dose and irradiated volume. Between November, 2009 and January, 2015, 9 consecutive patients with histologically proven angiosarcoma of the scalp and/or face who received image-guided brachytherapy were retrospectively evaluated. The median age of the patients was 83.4 years (range, 67.7-91.9 years). Of the 9 patients, 8 had no lymph node metastasis and 1 patient had cervical lymph node metastasis. The patients were irradiated with a dose of 3 Gy three times per week for varying lengths of time; 4 patients received a total dose of 60 Gy, 1 received 48 Gy and the 4 remaining patients received 45 Gy. The patient who received 48 Gy also underwent additional electron therapy of 16 Gy in 8 fractions. The overall survival, progression-free survival and local progression-free rates at 3 years were 50.8% [95% confidence interval (CI): 15.6-78.1%], 37.0% (95% CI: 6.8-69.3%) and 77.8% (95% CI: 36.5-93.9%), respectively. The local progression-free rate in the 4 patients who received a total of ≥60 Gy was statistically significantly better compared with that in the 5 patients who received a dose of

Purpose The present retrospective study assessed the role of proton beam therapy (PBT) in the treatment of patients with Stage II or III non–small-cell lung cancer who were inoperable or ineligible for chemotherapy because of co-existing disease or refusal. Patients and Methods Between November 2001 and July 2008, PBT was given to 35 patients (5 patients with Stage II, 12 with Stage IIIA, and 18 with Stage IIIB) whose median age was 70.3 years (range, 47.4–85.4). The median proton dose given was 78.3 Gy (range, 67.1–91.3) (relative biologic effectiveness). Results Local progression-free survival for Stage II-III patients was 93.3% at 1 year and 65.9% at 2 years during a median observation period of 16.9 months. Four patients (11.4%) developed local recurrence, 13 (37.1%) developed regional recurrence, and 7 (20.0%) developed distant metastases. The progression-free survival rate for Stage II-III patients was 59.6% at 1 year and 29.2% at 2 years. The overall survival rate of Stage II-III patients was 81.8% at 1 year and 58.9% at 2 years. Grade 3 or greater toxicity was not observed. A total of 15 patients (42.9%) developed Grade 1 and 6 (17.1%) Grade 2 toxicity. Conclusion PBT for Stage II-III non–small-cell lung cancer without chemotherapy resulted in good local control and low toxicity. PBT has a definite role in the treatment of patients with Stage II-III non–small-cell lung cancer who are unsuitable for surgery or chemotherapy.

To determine the effectiveness of high-dose conformal radiotherapy to the involved field for patients with Stage III non-small-cell lung cancer (NSCLC).Between May 1999 and April 2006, a total of 100 consecutive patients with inoperable Stage IIIA or IIIB NSCLC with a performance score of 0 to 2 and treatment by radical radiotherapy combined with chemotherapy were included. Up to August 2002, 33 patients underwent conventional radiotherapy of 56 Gy to 66 Gy using anteroposterior opposite ports to the primary tumor and elective lymph nodes (conventional group). After September 2002, the remaining 67 patients underwent high-dose radiotherapy of 66 Gy to 84 Gy to the involved volume with three-dimensional (3-D) conformal radiotherapy (conformal group).The median survival was 13.2 months (95% confidence interval [CI], 7.5-18.5 months) in the conventional group and 17.3 months (95% CI, 10.7- 24.0 months) in the conformal group. The overall survival at 3 years were 9.1% (95% CI, -0.7-18.9%) in the conventional group and 31.0% (95% CI, 18.9-43.1%) in the conformal group; the conformal group had a significantly better overall survival (p0.05). The radiotherapy method (hazard ratio = 0.55, p0.05) and performance status (hazard ratio = 1.48, p0.05) were shown to be statistically significant independent prognostic factors.Based on the practical experience reported here, 3-D conformal radiotherapy allowed dose escalation without excessive toxicity, and may improve overall survival rates for patients with Stage III NSCLC.

To evaluate the efficacy and safety of proton-beam therapy for locoregionally advanced esophageal cancer. The subjects were 51 patients with esophageal cancer who were treated between 1985 and 2005 using proton beams with or without X-rays. All but one had squamous cell carcinoma. Of the 51 patients, 33 received combinations of X-rays (median 46 Gy) and protons (median 36 GyE) as a boost. The median total dose of combined X-rays and proton radiation for these 33 patients was 80 GyE (range 70–90 GyE). The other 18 patients received proton-beam therapy alone (median 79 GyE, range 62–98 GyE). Treatment interruption due to radiation-induced esophagitis or hematologic toxicity was not required for any patient. The overall 5-year actuarial survival rate for the 51 patients was 21.1% and the median survival time was 20.5 months (95% confidence interval 10.9–30.2). Of the 51 patients, 40 (78%) showed a complete response within 4 months after completing treatment and seven (14%) showed a partial response, giving a response rate of 92% (47/51). The 5-year local control rate for all 51 patients was 38.0% and the median local control time was 25.5 months (95% confidence interval 14.6–36.3). The results suggest that proton-beam therapy is an effective treatment for patients with locally advanced esophageal cancer. Further studies are required to determine the optimal total dose, fractionation schedules, and best combination of proton therapy with chemotherapy.

Purpose To investigate the safety and efficacy of proton beam therapy (PBT) in patients with large hepatocellular carcinoma (HCC). Methods and Materials Twenty-two patients with HCC larger than 10 cm were treated with proton beam therapy at our institution between 1985 and 2006. Twenty-one of the 22 patients were not surgical candidates because of advanced HCC, intercurrent disease, or old age. Median tumor size was 11 cm (range, 10–14cm), and median clinical target volume was 567 cm3 (range, 335–1,398 cm3). Hepatocellular carcinoma was solitary in 18 patients and multifocal in 4 patients. Tumor types were nodular and diffuse in 18 and 4 patients, respectively. Portal vein tumor thrombosis was present in 11 patients. Median total dose delivered was 72.6 GyE in 22 fractions (range, 47.3–89.1 GyE in 10–35 fractions). Results The median follow-up period was 13.4 months (range, 1.5–85 months). Tumor control rate at 2 years was 87%. One-year overall and progression-free survival rates were 64% and 62%, respectively. Two-year overall and progression-free survival rates were 36% and 24%, respectively. The predominant tumor progression pattern was new hepatic tumor development outside the irradiated field. No late treatment-related toxicity of Grade 3 or higher was observed. Conclusions The Bragg peak properties of PBT allow for improved conformality of the treatment field. As such, large tumor volumes can be irradiated to high doses without significant dose exposure to surrounding normal tissue. Proton beam therapy therefore represents a promising modality for the treatment of large-volume HCC. Our study shows that PBT is an effective and safe method for the treatment of patients with large HCC.

The authors have published a series of studies evaluating the safety and efficacy of proton beam therapy for the treatment of hepatocellular carcinoma in a variety of clinical settings. In the current study, they retrospectively reviewed their entire experience treating hepatocellular carcinoma patients with proton beam therapy at their hospital-based facility at the University of Tsukuba.From November 2001 to December 2007, 333 patients with hepatocellular carcinoma were treated with proton beam therapy at the University of Tsukuba. A total of 318 patients were included in this study. Total dose delivered and fractionation scheme were determined by protocols that varied based on location of tumor. Survival rates and prognostic factors were assessed.Overall actuarial survival rates at 1-year, 3-years, and 5-years were 89.5% (95% confidence interval [95% CI], 85.7-93.1%), 64.7% (95% CI, 56.6-72.9%), and 44.6% (95% CI, 29.7-59.5%), respectively. Child-Pugh liver function (hazards ratio [HR], 2.84; P.01), T stage (HR, 1.94; P.05), performance status (HR, 2.12; P.01), and planning target volume (HR, 2.12; P.05) significantly impacted survival. The 3-year and 5-year survival rates were 69.1% (95% CI, 59.9-78.3%) and 55.9% (95% CI, 41.5-70.3%), respectively, for patients with Child-Pugh A disease and 51.9% (95% CI, 32.3-71.5%) and 44.5% (95% CI, 23.1-65.8%), respectively, for patients with Child-Pugh B disease. The actuarial survival rates of patients with Child-Pugh class A were statistically different between groups of planned target volumeor=125 mL and125 mL (P.05).The authors have shown proton beam therapy to be both safe and effective for the treatment of patients with hepatocellular carcinoma. They strongly recommend the consideration of proton beam therapy in patients for whom other treatment options are risky or contraindicated.

The prognosis of patients with advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is extremely poor, as effective treatment options are limited. The authors performed a retrospective review to evaluate the efficacy of proton-beam therapy (PBT) for patients presenting with PVTT in the setting of HCC.Between February 1991 and September 2005, 35 patients with HCC and tumor thrombi in the main trunk or major branches of the portal vein presented for consideration of PBT. Their tumor sizes ranged from 25 mm to 130 mm (median, 60 mm). A median total dose of 72.6 GyE in 22 fractions was delivered over 31 days to a target volume that encompassed both the primary hepatic lesion and the PVTT.32 patients were progression-free during a median follow-up period of 21 months (range, 2-88 months) and three patients experienced disease progression. Local progression-free survival rates were 46% at 2 years and 20% at 5 years, and the median local progression-free survival was 21 months. Acute toxicityor = grade 3 was observed in three patients, and no patient experienced late toxicityor = grade 3. None of the patients had to discontinue treatment as a result of toxicity.PBT improved local control and significantly prolonged survival in HCC patients with PVTT.

Background There are few reports of treatment and outcome for patients with metachronous or synchronous lung and gastric cancers. To evaluate them, we conducted a retrospective study. Patients and Methods The medical records of patients with lung cancer who previously or simultaneously had gastric cancer seen in our division between January 1979 and July 2008 were reviewed. Results Forty-five (3.2%) of 1391 patients had previous or simultaneous gastric cancer. The proportion of men was higher among patients with lung cancer with gastric cancer than those without ( P = .0006). There was a significant difference in age at the time of diagnosis of lung cancer between the 45 patients with gastric cancer and the 1346 patients without it ( P = .0344). The proportion of smokers was higher among lung cancer patients with gastric cancer than those without ( P = .0015). Twenty-seven of 45 patients had smoking-related cell types of lung cancer: squamous cell carcinoma and small-cell lung cancer. The proportion of these 2 cell types was higher in patients with lung cancer with gastric cancer than those without ( P = .02). The diagnosis of gastric cancer preceded the diagnosis of lung cancer in 33 patients, and the median duration from the diagnosis of gastric cancer to that of the lung cancer was 6 years. Conclusion For patients with gastric cancer, smoking cessation, a chest radiograph at least yearly for several years, and swift evaluation of signs or symptoms that are suggestive of lung cancer should be recommended, especially in elderly men with gastric cancer and smoking habit.

Purpose: To investigate the effect of proton beam therapy (PBT) on implanted cardiac pacemaker function. Methods and Materials: After a phantom study confirmed the safety of PBT in patients with cardiac pacemakers, we treated 8 patients with implanted pacemakers using PBT to a total tumor dose of 33-77 gray equivalents (GyE) in dose fractions of 2.2-6.6 GyE. The combined total number of PBT sessions was 127. Although all pulse generators remained outside the treatment field, 4 patients had pacing leads in the radiation field. All patients were monitored by means of electrocardiogram during treatment, and pacemakers were routinely examined before and after PBT. Results: The phantom study showed no effect of neutron scatter on pacemaker generators. In the study, changes in heart rate occurred three times (2.4%) in 2 patients. However, these patients remained completely asymptomatic throughout the PBT course. Conclusions: PBT can result in pacemaker malfunctions that manifest as changes in pulse rate and pulse patterns. Therefore, patients with cardiac pacemakers should be monitored by means of electrocardiogram during PBT.

We investigated whether scintigraphy was superior to radiography for detecting migrated seeds after brachytherapy for prostate cancer.We studied 57 patients with early prostate cancer who were treated with free (125)I transperineal brachytherapy. Scintigraphy was used to detect seed migration on postoperative day (POD) 1, radiography was used on POD 2, and both tests were used on POD 30.The total number of implanted seeds in this study was 3,753 in 57 patients. Overall, there were 19 seed migrations in 12 patients. On POD 1, there were 4 seed migrations in 4 patients that were detected by scintigraphy. On POD 2, there were 10 seed migrations in 9 patients that were detected by radiography. On POD 30, 17 seed migrations were detected in 10 patients by radiography and 18 seeds migrations were detected by scintigraphy. However, 1 seed migration which was located outside of the detectable range of radiography was detected only by scintigraphy.Both scintigraphy and radiography have similar abilities to detect migrated seeds 1 month after (125)I brachytherapy for prostate cancer. While both tests have advantages and disadvantages, it is reasonable to only use radiography if scintigraphy is not available.

The purpose of this study was retrospectively to evaluate the effectiveness of fractionated stereotactic radiotherapy (FSRT) for patients who presented with intracranial metastases as the initial symptom of lung carcinoma. Fifteen patients with three or fewer brain metastases from lung carcinoma underwent FSRT receiving 42 Gy in 7 fractions or 40 Gy in 4 fractions from April 1999 to October 2002. Patients who developed new lesions were retreated with FSRT or whole brain radiotherapy (WBRT). Tumor control was obtained in 14 patients during a median period of 21.0 months (ranging from 11 to 34 months) with salvage radiotherapy whenever required. None died from brain metastasis. The median survival time was 7.0+/-3.0 months and 21.0+/-1.0 months for patients with or without extracranial metastases, respectively (p

A patient with cryptogenic organising pneumonia after radiotherapy in the thorax was dramatically dissolved by administration of corticosteroid.

Background. The amount of dehydroascorbic acid contained within total ascorbic acid (oxidized as well as non-oxidized forms) in plasma, hereafter referred to as the dehydroascorbic acid fraction, may be a measure of oxidative stress during haemodialysis. In the present study, we determined this fraction in chronic haemodialysis patients. Methods. Using high performance liquid chromatography, dehydroascorbic acid and total ascorbic acid levels were measured in 80 maintenance haemodialysis patients for a period of >2 years as well as in 49 controls, to examine a possible association of these compounds with clinical parameters and/or drugs taken by the patients. Results. Dialysis patients who had an increased plasma urate level (P

Radiotherapy has been used to treat loco-regional recurrences located at various intra-thoracic sites, but longterm survival of these patients has been rarely observed. We report herein a lung adenocarcinoma patient with locoregional recurrence, who was successfully treated with high-dose radiotherapy. The patient could survive with no evidence of recurrence 5 years after thoracic irradiation. It is probably safe to administrate high-dose radiotherapy for some loco-regional recurrent patients with favorable prognostic factors such as good PS, no body weight loss. Further studies will be required to define a favorable subset of patients most likely to benefit from an aggressive approach.

Technical aspects of fractionated stereotactic radiotherapy for solitary hepatocellular carcinoma have been investigated. Precise positioning of the patient and substantial reduction of the liver movement due to respiration were achieved by placing the patient ventrally on the treatment couch without a body cast. Repeated CT examinations were required for verification of tumor targeting. Though there were geometrical limitations on gantry rotation when the linac couch was rotated from its standard position, dose distributions obtained were found to be excellent. A patient with a small solitary lesion in the posterior segment of the liver received 52 Gy in 13 fractions over 29 days. He tolerated the treatment well without experiencing any morbidities or deterioration of liver functions. Three months later his alpha-fetoprotein value returned to normal and CT examinations revealed tumor shrinkage as well as a reduction in the viability of the tumor cells. The results suggest that it is possible to overcome technical difficulties associated with fractionated stereotactic radiotherapy of intraabdominal tumors.

Cryptogenic organizing pneumonia (COP) following radiotherapy is occasionally diagnosed as radiation pneumonitis or bacterial pneumonia. The current study presents two cases of COP following radiotherapy: A 48-year-old premenopausal female with breast cancer and an 84-year-old male with non-small cell lung cancer. In the cases of breast cancer and lung cancer, patients were first diagnosed with bacterial pneumonia and radiation pneumonitis, respectively. In the two cases, computed tomography disclosed the migration of ground glass shadows, which were finally resolved without any fibrotic changes. The two cases were finally diagnosed as COP associated with radiotherapy. When an infiltrating shadow is present outside of the irradiated field, COP must be included in the differential diagnosis.

To retrospectively investigate the biochemical outcome following delayed radiotherapy in patients with prostate cancer.From July 2000 to November 2008, 144 consecutive patients with localized prostate cancer underwent radiotherapy and androgen-deprivation therapy. Biochemical progression-free survival was compared in patients who began radiotherapy6 months (delayed group) with these who began ≤ 6 months (non-delayed group) from diagnosis by biopsy. Treatment selection bias was adjusted by the propensity score method.After a median follow-up of 64 months, the 5-year biochemical progression-free survival of the delayed and non-delayed groups was 87.4% (95% confidence interval, CI=69.7-95.1%) and 96.6% (95% CI=89.6-98.9%), respectively (p=0.03). Delayed radiotherapy was the only independent risk factor for biochemical progression (hazard ratio=3.97, 95% CI 1.07-14.7, p=0.04). The results were validated by propensity score analysis.Delaying radiotherapy by6 months increases the risk of biochemical progression in patients with localized prostate cancer.

Patients with T3 or more squamous cell esophageal cancer underwent low-dose preoperative radiotherapy with chemotherapy, to reduce local recurrence, followed by surgery. The aim was to ascertain tumor response and assess prognostic factors.Between May 2002 and June 2011, 37 consecutive patients with esophageal cancer underwent chemoradiotherapy followed by surgery. The numbers of patients in clinical stages IIA/IIIA/IIIB/IIIC were 2/24/7/4, respectively. All were given a dose of 30 Gy in 15 fractions, with concurrent chemotherapy using cisplatin and fluorouracil. Curative surgery was performed a median of 1.2 months after completion of chemoradiotherapy.Based on the findings from surgery, 26 patients (70%) achieved a stage reduction and six patients (16%) had a complete pathological response. The numbers of patients undergoing resections microscopically complete, with microscopically positive margins, and macroscopically positive margins were 33, 3, and 1, respectively. During a median follow-up period of 22.5 months, the two-year progression-free survival and overall survival were 62.1% [95% confidence interval (CI)=45.8 to 78.4%] and 71.9% [95% CI=55.1 to 88.7%], respectively. Statistically significant prognostic factors for overall survival were age [hazard ratio=6.6; 95% CI=1.1 to 38; p=0.04] and pathological T factor [hazard ratio=10.2; 95% CI=1.4 to 77; p=0.02]. No patients died as a result of surgery.Seventy percent of patients with esophageal cancer who received radiotherapy dose of 30 Gy in 15 fractions combined with chemotherapy achieved a stage reduction with low toxicity.

Pancreatic cancer shows high mortality and has a poor prognosis. Although the rate of response to all chemotherapeutic regimens is low, some patients have shown improvement of their symptoms after chemotherapy and/or radiotherapy without obvious tumor regression. We assessed the clinical benefit of systemic combined chemotherapy with 5-fluorouracil and cisplatin (FP therapy) in 21 patients with advanced cancer of the pancreas. The clinical response to FP therapy was evaluated using two parameters: pain (intensity of pain and consumption of morphine) and performance status. A patient was considered to be a clinical responder if one of two parameters was positive and the other was positive or stable. Four patients (19%) responded. Two of the responders achieved partial response according to the objective tumor response, and the remaining two showed no change. The survival period in responders was significant longer than in the other patients. The clinical response may be one parameter for evaluating the results of treatment for pancreatic cancer, and the longer survival period of the clinical responders in this study supports this notion.

This study aimed to retrospectively evaluate the efficacy of radiotherapy for primary intraocular non-Hodgkin lymphoma (PIOL). Between May 1998 and October 2010, 22 immunocompetent patients (four men, 18 women; median age 70 years, range 53-79 years) were diagnosed with PIOL. Magnetic resonance imaging showed no intracranial involvement in any patient. Patients received radiotherapy at a median total dose of 30 Gy (range 30-40 Gy). Three-year overall survival, progression-free survival and local control rates were 89% (95% confidence interval [CI]: 75, 103), 49% (95% CI: 24, 73) and 95% (95% CI: 86, 105) over a median of 36 months of observation, respectively. Twelve patients (55%) had intracranial relapse at a median of 28 months after initiation of radiotherapy. Visual acuity improved or was stable in 81% of treated eyes. The only grade ≥ 3 toxicity was cataract formation (five patients). Radiotherapy without chemotherapy for PIOL achieved high local control rates with acceptable toxicities.

In advanced-stage disease of certain thoracoabdominal tumors, proton therapy (PT) with concurrent chemotherapy may be an option to reduce side effects. Several technological developments, including a respiratory gating system and implantation of fiducial markers for image guided radiation therapy (IGRT), are necessary for the treatment in thoracoabdominal tumors. In this chapter, the role of PT for tumors of the lung, the esophagus, and liver are discussed.

We report a rare case of chronic eosinophilic pneumonia with subpleural curvilinear shadow. CT scan showed a patchy consolidation in the bilateral upper lungs. In addition, subpleural curvilinear shadow was found in the bilateral upper lungs. A bronchoalveolar lavage obtained from the right middle lobe showed 25 % eosinophils. Although very rare, we should therefore keep in mind that patients, who have patchy consolidation with areas of subpleural curvilinear shadow in the bilateral upper lungs, may have chronic eosinophilic pneumonia.

Purpose To retrospectively evaluate the effectiveness of fractionated stereotactic radiotherapy (FSRT) for craniopharyngioma. Methods and Materials Between 1999 and 2005, 16 patients with craniopharyngioma were referred to Tokyo Medical University Hospital. They received FSRT alone after histologic confirmation by needle biopsy and underwent cyst drainage via endoscopy. The median prescription dose fraction was 30 Gy in six fractions. All patients except 1 were followed up until December 2009 or death. Results The median follow-up period was 52 months (range, 4–117 months). Of the 17 patients, 3 experienced recurrence 4 to 71 months after FSRT. The 3-year local control rate was 82.4%. One patient died of thyroid cancer, and the 3-year survival rate was 94.1%. Eight patients had improved visual fields at a median of 2.5 months after FSRT, but hormonal functions did not improve in any patient. Conclusions FSRT after cyst drainage seems to be safe and effective for patients with craniopharyngiomas, and it may be a safe alternative to surgery.

Purpose To evaluate the safety and effectiveness of proton beam therapy for hepatocellular carcinoma (HCC) located adjacent to the alimentary tract. Patients and Methods Forty-seven patients (median age, 69 years; range, 43–82 years) who had HCC located within 2 cm of the alimentary tract underwent proton beam therapy. Liver damage according to the Child-Pugh classification was Class A in 35 patients, Class B in 9, and Class C in 3. Treatment protocols of the early 16 patients and the late 31 patients were 72.6 GyE in 22 fractions and 77 GyE in 35 fractions, respectively. Results During the median follow-up period of 23 months, 24 patients died; the remaining 23 patients were alive until September 2008. The median overall survival was 33.9 months (95% confidence interval [CI], 10.8–57.0 months). Actuarial overall and local progression-free survival rates at 3 years were 50.0% and 88.1%, respectively. Grade 2 and 3 alimentary tract hemorrhage was observed in 3 (6.4%) and 1 (2.1%) patients, respectively. Conclusions Our proton beam therapy strategy for HCC located adjacent to the alimentary tract seems to be effective but should be performed with caution.

Malignant myoepithelioma of the head and neck usually arises in the salivary glands. We experienced a rare case with malignant myoepithelioma in the maxillary sinus. A 47-year-old woman with malignant myoepithelioma in the maxillary sinus underwent partial maxillectomy. However, local recurrence occurred 28 months after surgery and she was subsequently treated with radiation therapy with proton beams. The recurrent tumor showed complete response and the patient was alive with no evidence of disease 30 months after irradiation. No therapy-related severe toxicities were observed. A rare case with malignant myoepithelioma in the maxillary sinus was successfully treated with radiation therapy.

To investigate technical feasibilities of noncoplanar proton-beam therapy (PBT) on dose reduction to critical organs. The degree of mechanical precision, rotational limitations of the gantry and the treatment couch were evaluated, and dose-volume histograms were compared for noncoplanar and coplanar PBT. Following these studies, three patients with tumors proximal to the optic nerve underwent noncoplanar PBT. Noncoplanar PBT offered advantage in dose reduction to the optic nerve when compared to coplanar therapy. This advantage was more significant if the tumor reduced in size during treatment. None experienced radiation injury to the optic nerve during a short follow-up time of 7–12 months. Noncoplanar PBT appears to reduce doses to organs at risk.