Comparison of proton-based definitive chemoradiotherapy and surgery-based therapy for esophageals cell carcinoma: a multi-center retrospective Japanese cohort study.

BACKGROUND: Proton-based, definitive chemoradiotherapy (P-CRT) for esophageal squamous cell carcinoma (ESCC) previously showed comparable survival outcomes with the surgery-based therapy, i.e., neoadjuvant chemotherapy followed by esophagectomy (NAC-S), in a single-institutional study. This study aimed to validate this message in a Japanese multicenter study. METHODS: Eleven Japanese esophageal cancer specialty hospitals have participated. A total of 518 cases with clinical Stage I-IVA ESCC between 2010 and 2019, including 168 P-CRT and 350 NAC-S patients, were enrolled and long-term outcomes were evaluated. Propensity-score weighting analyses with overlap weighting for confounding adjustment were used. RESULTS: The 3-year overall survival (OS) of the P-CRT group was equivalent to the NAC-S group (74.8% vs. 72.7%, hazard ratio [HR]: 0.87, 95% confidence interval [CI]: 0.61-1.25). Although, the 3-year P-CRT group progression-free survival (PFS) was inferior to the NAC-S group (51.4% vs. 59.6%, HR 1.39, 95% CI 1.04-1.85), the progression P-CRT group cases showed better survival than the NAC-S group (HR 0.58, 95% CI 0.38-0.88), largely because of salvage surgery or endoscopic submucosal dissection for local progression. The survival advantage of P-CRT over NAC-S was more pronounced in the cT1-2 (HR 0.61, 95% CI 0.29-1.26) and cStage I-II (HR 0.50, 95% CI 0.24-1.07) subgroups, although this trend was not evident in other populations, such as cT3-4 and cStage III-IVA. CONCLUSIONS: Proton-based CRT for ESCC showed equivalent OS to surgery-based therapy. Especially for patients with cT1-2 and cStage I-II disease, proton-based CRT has the potential to serve as a first-line treatment.

Late Changes in Renal Volume and Function after Proton Beam Therapy in Pediatric and Adult Patients: Children Show Significant Renal Atrophy but Deterioration of Renal Function Is Minimal in the Long-Term in Both Groups.

To compare late renal effects in pediatric and adult patients with malignancies after PBT involving part of the kidney. A retrospective study was conducted to assess changes in renal volume and function in 24 patients, including 12 children (1-14 years old) and 12 adults (51-80 years old). Kidney volumes were measured from CT or MRI images during follow-up. Dose-volume histograms were calculated using a treatment planning system. In children, the median volume changes for the irradiated and control kidneys were -5.58 (-94.95 to +4.79) and +14.92 (-19.45 to +53.89) mL, respectively, with a relative volume change of -28.38 (-119.45 to -3.87) mL for the irradiated kidneys. For adults, these volume changes were -22.43 (-68.7 to -3.48) and -21.56 (-57.26 to -0.16) mL, respectively, with a relative volume change of -5.83 (-28.85 to +30.92) mL. Control kidneys in children exhibited a marked increase in size, while those in adults showed slight volumetric loss. The percentage of irradiated volume receiving 10 Gy (RBE) (V10) and 20 Gy (RBE) (V20) were significantly negatively associated with the relative volume change per year, especially in children. The CKD stage based on eGFR for all patients ranged from 1 to 3 and no cases with severe renal dysfunction were found before or after PBT. Late effects on the kidneys after PBT vary among age groups. Children are more susceptible than adults to significant renal atrophy after PBT. V10 and V20 might serve as predictors of the degree of renal atrophy after PBT, especially in children. PBT has a minimal impact on deterioration of renal function in both children and adults.

Re-Irradiation With Proton Beam Therapy for Localized Perineural Spread Following Presacral Recurrence in Sigmoid Colon Cancer: A Case Report.

This report describes the effective management of localized perineural spread (PNS) to the sacral peripheral nerves following a presacral recurrence of colon cancer using proton beam therapy (PBT). The patient, a male in his 60s with a history of sigmoid colon cancer treated with laparoscopic Hartmann's procedure, presented with presacral recurrence two years post-surgery. Radical resection was deemed infeasible, leading to a combined treatment of PBT (75 Gy relative biological effectiveness (RBE) in 25 fractions) and capecitabine. However, three years post-PBT, magnetic resonance imaging revealed swelling of the left S2 nerve with abnormal fluorodeoxyglucose uptake, indicating localized PNS. Re-irradiation with PBT (75 Gy RBE in 25 fractions) was conducted, carefully considering the overlap with the previous PBT field and aiming to minimize dosage to adjacent organs. At 1.5 years post-reirradiation, the patient remained free of recurrence. This case underscores the potential efficacy of PBT and emphasizes the need for further research to assess its broader applicability in comparable situations.

Tumor Response on Diagnostic Imaging after Proton Beam Therapy for Hepatocellular Carcinoma.

BACKGROUND: Follow-up after treatment for hepatocellular carcinoma (HCC) can be mostly performed using dynamic CT or MRI, but there is no common evaluation method after radiation therapy. The purpose of this study is to examine factors involved in tumor reduction and local recurrence in patients with HCC treated with proton beam therapy (PBT) and to evaluate HCC shrinkage after PBT. METHODS: Cases with only one irradiated lesion or those with two lesions irradiated simultaneously were included in this study. Pre- and post-treatment lesions were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) by measuring the largest diameter. RESULTS: The 6-, 12-, and 24-month CR + PR rates after PBT were 33.1%, 57.5%, and 76.9%, respectively, and the reduction rates were 25.1% in the first 6 months, 23.3% at 6-12 months, and 14.5% at 13-24 months. Cases that reached CR/PR at 6 and 12 months had improved OS compared to non-CR/non-PR cases. CONCLUSIONS: It is possible that a lesion that reached SD may subsequently transition to PR; it is reasonable to monitor progress with periodic imaging evaluations even after 1 year of treatment.

A case of massive hemoptysis caused by lung cancer saved by V-V ECMO and hemostasis achieved by radiotherapy.

Massive hemoptysis is one of the fatal complications of lung cancer. There is no established standard treatment method for it, and it often causes sudden suffocation, and some cases may be difficult to save. A 63-year-old man was admitted to the hospital with dyspnea, and developed massive hemoptysis from lung cancer shortly after admission. The tumor had obstructed the right main bronchus and had invaded the right pulmonary artery. Surgery and interventional radiology were judged impossible. The patient was successfully saved by the introduction of Veno-Venous Extra Corporeal Membrane Oxygenation (V-V ECMO), and hemostasis was obtained by radiotherapy. Two months after completion of radiotherapy, he was weaned off the ventilator and discharged on his own. He died of increased peritoneal dissemination and other complications 1 year and 1 month later, but no recurrence of hemoptysis was noted until his death. We experienced a case of massive hemoptysis in which V-V ECMO and radiation therapy succeeded in saving life and stopping bleeding. The use of V-V ECMO by emergency care teams and multimodality therapy, including radiotherapy, were effective for massive hemoptysis from lung cancer.

Retrospective Analysis of the Areas Responsible for Light Flash and Odor During Proton Beam Therapy and Photon Therapy.

Background Abnormal sensations were frequently experienced by patients who received irradiation of the brain or head and neck region. We have previously suggested correlations with irradiation of the nasal cavity and retina. Purpose We performed a retrospective dose-volume histogram analysis focused on the brain and head and neck tumor to examine the relationship between these abnormal sensations and the details of irradiation. Methods Multivariate logistic regression models were applied for the presence or absence of light flash and odor. Gender, age, radiotherapy method (proton beam therapy vs. photon radiotherapy), dose of retina, optic nerve, chiasmatic gland, pituitary, nasal cavity, oral cavity, frontal lobe, parietal lobe, occipital lobe, temporal lobe, amygdala, and hippocampus were set as candidates of explanatory variables. Results Light flash and odor during radiotherapy have been suggested to be associated with younger age and retina and nasal cavity irradiation. Multivariate analyses including dose-volume histograms indicated that light flash was related to age, chiasmatic gland irradiation, and pituitary dose, and odor was related to age and nasal cavity irradiation. Conclusion Our results indicate that light flash during radiotherapy is caused by irradiation of the visual pathway and that odor is caused by irradiation of the nasal cavity or olfactory bulb.

Synchronization of light flash with the irradiation pulse in proton beam therapy: A case report.

The correlation between sensory light flash and proton beam delivery was evaluated by measuring the timing of pulse beam delivery and light flash sensing using an event recorder in an 83-year-old patient receiving proton beam therapy (PBT) for nasopharyngeal adenoid cystic carcinoma. The treatment dose was 65 Gy (RBE) in 26 fractions with 2 ports, and both beams included the visual pathway (retina, optic nerve, chiasma). Measurements were obtained in 13 of the 26 fractions. The patient sensed a light flash in all 13 fractions and pressed the recorder button for 426 of the 430 pulsed beam deliveries, giving a sensing rate of 99.1%. The median duration of button-pressing of 0.3 s was almost the same as that of the beam pulse of 0.2 s, with a reaction time lag of 0.35 s. These results suggest a consistency between light flash during PBT and the timing of irradiation.

Clinical Impact of Proton Beam Therapy for Postoperative Lymph Node Oligorecurrence of Esophageal Cancer.

BACKGROUND/AIM: Radiotherapy is a salvage therapy type for postoperative recurrence of esophageal cancer. Compared to conventional photon-based radiotherapy, proton beam therapy can reduce the irradiated dose to the surrounding organs, facilitating the management of patients who are unfit for radiotherapy. In this study, the outcomes and toxicity of proton beam therapy for postoperative lymph node oligorecurrence of esophageal cancer were investigated. PATIENTS AND METHODS: We retrospectively evaluated the clinical outcomes and toxicity of 13 sites in 11 patients treated with proton beam therapy for postoperative lymph node oligorecurrence of esophageal cancer. In total, eight men and three women with a median age of 68 years (range=46-83 years) were included. RESULTS: The median follow-up period was 20.2 months. During the follow-up period, four patients died of esophageal cancer. Eight of the 11 patients developed recurrence; of these, seven patients had recurrence outside the irradiated field, and one had recurrence inside and outside the irradiated field. The 2-year overall survival, progression-free survival, and local control rates were 48.0%, 27.3%, and 84.6%, respectively. The median survival time was 22.4 months. There were no severe acute or late adverse events. CONCLUSION: Proton beam therapy could be a safe and effective treatment method for postoperative lymph node oligorecurrence of esophageal cancer. It may be beneficial even in cases where conventional photon-based radiotherapy is difficult to administer in combination with increased doses or with chemotherapy.

Stereotactic Body Radiotherapy for Stage I Lung Cancer With a New Real-time Tumor Tracking System.

BACKGROUND/AIM: Suppression of respiratory movement is crucial for safe and effective stereotactic body radiotherapy (SBRT). SyncTraX FX4 is a novel device for synchronous respiratory irradiation. The purpose of this study was to evaluate the efficacy and toxicity of SBRT using SyncTraX FX4 for patients with lung cancer. PATIENTS AND METHODS: Patients treated with SBRT using SyncTraX FX4 between November 2017 and August 2020 were included. In all cases, fiducial markers were inserted into the lung, and the total dose administered was 55 or 60 Gy, depending on the distance from the central region of the lung. Acute and late toxicities were reported, and local control, progression-free survival, cancer-specific survival, and overall survival were analyzed. RESULTS: We evaluated 16 patients and 17 sites. The median follow-up period was 14.4 months. In both the acute and late phases, one patient experienced grade 3 radiation pneumonitis; however, grade 4 or higher toxicities were not observed. There was no local recurrence during the observation period, and the overall survival, cancer-specific survival, and progression-free survival at 2 years were 54.6%, 85.1%, and 33.7%, respectively. CONCLUSION: SBRT with SyncTraX FX4 can provide safe and effective treatment for lung cancer patients in poor condition.

A Case Report of Radiotherapy for Skull Lesions of Langerhans Cell Histiocytosis With Dural Invasion.

Background: Langerhans cell histiocytosis (LCH) is a rare disease, especially in adults. It is often associated with non-fatal bone and skin lesions and has relatively good radiosensitivity. In contrast, brain and lymph node metastases from LCH lesions are considered to be less sensitive to radiotherapy. Case Report: At our institution, 30 Gy radiotherapy was used to treat bone lesions with dural invasion in a patient with adult-onset LCH. The patient was treated with chemotherapy and radiotherapy for 21 years since the initial diagnosis. After radiotherapy, the tumor shrank rapidly, and a complete response was achieved 1 year after treatment. The patient survived without local recurrence. Conclusion: Here, we report the details of this case, along with a review of the literature. We suggest that even with invasion of the tissues around the bone lesions in LCH, local recurrence can be prevented by middle radiation doses.

A Recurrent Solitary Fibrous Tumor With an Exceptional Response to Low-Dose Radiotherapy: A Case Report and Literature Review.

Solitary fibrous tumor (SFT) is a soft tissue tumor derived from mesenchymal cells. We report a case of a giant SFT with insulin-like growth factor 2 (IGF-2) production in the pelvis of an 85-year-old male. SFT was diagnosed in surgery for a complaint of left lower abdominal distension. Subsequent tumor recurrence and progression caused rectal passage obstruction and hypoglycemia. Low-dose radiotherapy of 15 Gy in five fractions was started five years and four months after surgery, initially for a huge tumor around the rectum to improve rectal passage obstruction. The tumor volume shrank from 1054 cc before irradiation to 449 cc at one month and 396 cc at 10 months after irradiation. He had reached 90 years old at that time. Two months after the initial irradiation, similar radiotherapy of 15 Gy in five fractions was performed for a huge tumor in the right abdominal cavity. This tumor decreased from 1874 cc before irradiation to 615 cc at two months and 556 cc at seven months after irradiation. Dexamethasone (2.5 mg) was used for paraneoplastic syndrome at the time of initial radiation but was then reduced and became unnecessary two months after the second irradiation. Acute and late adverse events were mild. The patient is alive 60 months after the first irradiation. This case suggests that low-dose radiotherapy is beneficial as palliative therapy for symptom relief in patients with SFT.

A novel method for skin marking in radiotherapy: first clinical use of temporary organic tattoo seal.

An oil-based pen is widely used as a skin marker for identification of the isocenter and computed tomography (CT)-coordinate origin during radiotherapy. However, use of this pen has some disadvantages, including color loss and color migration. To address these problems, we have developed use of a temporary fashion tattoo (Inkbox) for skin marking. The utility and feasibility of Inkbox as an alternative to an oil-based pen were evaluated in this study. The study included patients from two centers who required skin marking for radiotherapy performed between December 2020 and March 2021. Skin markings were made with an oil-based pen or with Inkbox. The durability was recorded during daily irradiation. Skin markings with Inkbox were made in 32 patients. The total number of skin markings was 94: 64 with Inkbox and 30 with an oil-based pen. A questionnaire survey to evaluate each method was conducted among patients after radiotherapy. The median durations of marking were 16 and 4 days with Inkbox and an oil-based pen, respectively (p-value < 0.001). The survey showed that Inkbox had less impact on the daily lives of patients, including reduced color migration to clothes and less concern about disappearance of the marking. There were no adverse cutaneous side effects with Inkbox. The duration of marking with Inkbox is about 16 days, with little impact on daily life. These findings suggest that Inkbox is a potentially useful method of skin marking in radiotherapy.

Risk factor of pneumonitis on dose-volume relationship for chemoradiotherapy with durvalumab: Multi-institutional research in Japan.

OBJECTIVES: To estimate appropriate dose-volume parameters for avoidance of pneumonitis in use of chemoradiotherapy and durvalumab for treatment of lung cancer. MATERIALS AND METHODS: Patients with non-small cell lung cancer treated with concurrent chemoradiotherapy followed by durvalumab at 9 centers were enrolled in the study. Three-dimensional radiotherapy, intensity modulated radiotherapy, and proton beam therapy were used. The frequency and severity of pneumonitis and the dose-volume relationship for normal lung were evaluated. Univariable and multivariable analyses were conducted to identify risk factors. A covariate adjusted hazard ratio was then estimated for the percentages of normal lung volume irradiated at ≥ X Gy (Vx) (X = 5-40) and lung volume non-irradiated at ≥ X Gy (X = 5-40), with the covariates selected in the variable selection. Cumulative incidence functions and covariate adjusted hazard ratios were also estimated for dichotomized variables, with estimated cut-off points. RESULTS: A total of 91 patients were enrolled in the study. The median time from the start of radiotherapy to development of pneumonitis was 4.1 months. Pneumonitis was observed in 80 patients (88%), including grade 2 or severe pneumonitis in 31 (34%) and ≥ grade 3 pneumonitis in 11 (12%). Pneumonitis was inside the irradiation field in 73 of the 80 patients (91%). The selected factors for ≥ grade 2 pneumonitis were V20, and primary site (upper lobe) in multivariable analysis. The cut off value of V20 was 18.99%, and there was a significant difference between V20 of < 18.77 and ≥ 18.77. CONCLUSION: Though there are some limitation of this study, the basic concept of concurrent chemoradiotherapy with an emphasis on V20 remains unchanged in use of durvalumab. However, we recommend reduction of V20 to as small a value as possible in use of this therapy.

Impact of pre-brachytherapy magnetic resonance imaging on dose-volume histogram of locally advanced cervical cancer patients treated with radiotherapy including high-dose-rate brachytherapy.

PURPOSE: This study investigated the suitability of brachytherapy technique selection based on pre-brachytherapy magnetic resonance imaging (MRI) findings in cervical cancer by evaluating dose-volume histogram parameters. MATERIAL AND METHODS: We retrospectively evaluated data from 61 patients with cervical cancer who underwent pre-brachytherapy MRI within 7 days before their first high-dose-rate brachytherapy treatment, selected according to pre-brachytherapy MRI findings. Combined intracavitary brachytherapy with interstitial techniques (IC/ISBT) or interstitial brachytherapy (ISBT) were favored treatments for poor-responding tumors after concurrent chemoradiotherapy, asymmetrical tumors, bulky parametrial extensions, bulky primary disease, and extensive paravaginal or distal vaginal involvement. Intracavitary brachytherapy (ICBT) was the preferred treatment for small tumors without extensive involvement of the vagina and parametrium. RESULTS: The median tumor size was 58 mm on pre-treatment MRI and 38 mm on pre-brachytherapy MRI. On pre-brachytherapy MRI, 13 patients had a tumor with severe vaginal invasion, 15 patients presented with an asymmetrical bulky tumor, and 4 patients had bulky residual tumors. IC/ISBT or ISBT were administered to 26 patients (43%). Median equivalent dose in 2 Gy fractions of clinical target volume D90 was 70.8 Gy for all patients. Median clinical target volume D90 in each brachytherapy session exceeded the prescribed dose in both patients treated with ICBT and IC/ISBT or ISBT. Median equivalent dose in 2 Gy fractions of D2cc to the bladder, sigmoid colon, and rectum was 69.5, 52.0, and 58.4 Gy, respectively. All cases remained within the doses recommended for organs at risk. CONCLUSIONS: Pre-brachytherapy MRI may be helpful in selecting suitable candidates for each type of brachytherapy and deliver the recommended doses to the tumor and organs at risk, particularly in cases with large tumors, poor response to concurrent chemoradiotherapy, asymmetrical tumors, severe vaginal invasion, extensive parametrial invasion, and/or corpus invasion.

Long-term clinical outcomes of patients receiving proton beam therapy for caudate lobe hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) located in the caudate lobe (caudate HCC) is rare; however, patients with this type of tumour have poorer prognoses than those with HCC in other segments. Despite many published reports on the clinical usefulness of proton beam therapy (PBT) for HCC, data on the clinical outcomes of patients undergoing PBT for caudate HCC remain scarce. Therefore, the present study aimed to investigate the outcomes of this group of patients. Thirty patients with caudate HCC who underwent definitive PBT between February 2002 and February 2014 were retrospectively analysed. The total irradiation doses ranged from 55 to 77 (median 72.6) Gy relative biological dose. The median follow-up period was 37.5 (range, 3.0-152.0) months. The overall survival (OS) rates at one, three and five years were 86.6%, 62.8% and 46.1%, respectively. According to univariate and multivariate analyses, Child-Pugh A (P < 0.01), having a single tumour (P = 0.02) and a low serum alpha-fetoprotein level (AFP; P < 0.01) were significant factors predicting longer survival. The local control (LC) rates at one, three and five years were 100%, 85.9% and 85.9%, respectively, while the corresponding progression-free survival (PFS) rates were 65%, 27.5% and 22%, respectively. No grade 3 or worse adverse events were observed. PBT is effective and safe for the treatment of caudate HCC, and should therefore be considered a feasible option for intervention in patients with this disease.

Proton beam therapy for a giant hepatic hemangioma: A case report and literature review.

BACKGROUND: Hepatic hemangiomas are benign tumors with a favorable prognosis, but giant hepatic hemangiomas can cause abdominal symptoms and are indicated for treatment. Most cases are treated with surgery, but radiotherapy has also been used. However, to date, there have been no reports of proton beam therapy for a hepatic hemangioma. CASE PRESENTATION: A 46-year-old woman had a tumor of 80 × 80 mm in the left medial lobe of the liver, which was diagnosed as a giant hemangioma based on the contrast pattern. Therapy was required for a giant hepatic hemangioma with symptoms, but the patient refused blood transfusion due to religious reasons, which made surgical resection difficult. Therefore, she was referred to our hospital for proton beam therapy. At her first visit, liver function was Child-Pugh A (5 points) and there was no elevation of tumor markers. Proton beam therapy of 28.6 Gy (RBE) given in 13 fractions was performed without interruption. The only observed acute radiation toxicity was Grade 1 dermatitis. One year after proton beam therapy, the hemangioma had significantly decreased, and a complete response has been maintained for 15 years based on ultrasound and MRI. CONCLUSION: This case is the first reported use of proton beam therapy for a hepatic hemangioma. The outcome suggests that this treatment may be effective for a giant liver hemangioma.

Transitions of Liver and Biliary Enzymes during Proton Beam Therapy for Hepatocellular Carcinoma.

Proton beam therapy (PBT) is a curative treatment for hepatocellular carcinoma (HCC), because it can preserve liver function due to dose targeting via the Bragg peak. However, the degree of direct liver damage by PBT is unclear. In this study, we retrospectively analyzed liver/biliary enzymes and total bilirubin (T-Bil) as markers of direct liver damage during and early after PBT in 300 patients. The levels of these enzymes and bilirubin were almost stable throughout the treatment period. In patients with normal pretreatment levels, aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), and T-Bil were abnormally elevated in only 2 (1.2%), 1 (0.4%), 0, 2 (1.2%), and 8 (3.5%) patients, respectively, and in 8 of these 13 patients (61.5%) the elevations were temporary. In patients with abnormal pretreatment levels, the levels tended to decrease during PBT. GGT and T-Bil were elevated by 1.62 and 1.57 times in patients who received 66 Gy (RBE) in 10 fractions and 74 Gy (RBE) in 37 fractions, respectively, but again these changes were temporary. These results suggest that direct damage to normal liver caused by PBT is minimal, even if a patient has abnormal pretreatment enzyme levels.

Normal liver tissue change after proton beam therapy.

PURPOSE: Normal liver tissue changes after proton beam therapy (PBT) were investigated in patients at 1 and 2 years after the therapy. MATERIALS AND METHODS: Changes in normal liver tissue volume were examined. The dose distribution of the normal liver tissue was also simulated on the follow-up CTs. RESULTS: The normal liver tissue volume was 1149 ± 215 cm3 before treatment, 1089 ± 188 cm3 at 1 year, and 1080 ± 236 cm3 at 2 years after treatment. The normal liver tissue volume was increased in 10 and decreased in 20 patients at 2 years and was smaller than that before the treatment in total (P = 0.03). The simulated volume that received more than 30 Gray equivalent [V30 (cm3)] at 1 year was 258 ± 187 cm3 and that at 2 years (244 ± 171 cm3) was smaller than that before treatment (297 ± 140 cm3) (P = 0.03). CONCLUSIONS: The changes in the shape and volume of normal liver tissue are not constant, which cause a large dose distribution discrepancy in the normal liver for 2 years. Therefore, careful consideration of the dose distribution of normal liver tissue is required when planning re-irradiation.

Simulation study of dosimetric effect in proton beam therapy using concomitant boost technique for unresectable pancreatic cancers.

PURPOSE: The purpose of this study is to investigate the dose distribution of proton beam therapy (PBT) using a concomitant boost technique for unresectable pancreatic cancers. MATERIALS AND METHODS: This simulation study involved 36 patients with unresectable pancreatic cancer. The irradiation dose was set as 67.5 gray equivalent (GyE) with 25 fractions using concomitant boost technique. The irradiation dose was set as 50 GyE to cover the whole target and another posterior beam of 17.5 GyE was added to ensure that 10% isodose line was not delivered to the gastrointestinal (GI) tract. Dose distribution of the gross tumor volume and GI tract was examined. RESULTS: V55GyE, 60GyE, 65GyE were 80.8, 66.5, and 42.4%, respectively, and mean dose was 64.1 GyE in all patients. The distance from the GI tract showed significant difference in dose distribution (P = 0.002 in V55GyE, 0.0009 in V60GyE, 0.003 in V65GyE, and 0.02 in mean dose, respectively). Location, tumor diameter, or lymph nodes metastasis did not show any difference. CONCLUSIONS: We found that irradiated dose is closely related to the distance from the GI tract. Clinically, this protocol is expected to have outstanding effects on local control of tumors compared to conventional PBT.

The ruthenium-catalyzed reduction and reductive N-alkylation of secondary amides with hydrosilanes: practical synthesis of secondary and tertiary amines by judicious choice of hydrosilanes.

A triruthenium cluster, (mu3,eta2,eta3,eta5-acenaphthylene)Ru3(CO)7 (1) catalyzes the reaction of secondary amides with hydrosilanes, yielding a mixture of secondary amines, tertiary amines, and silyl enamines. Production of secondary amines with complete selectivity is achieved by the use of higher concentration of the catalyst (3 mol %) and the use of bifunctional hydrosilanes such as 1,1,3,3-tetramethyldisiloxane. Acidic workup of the reaction mixture affords the corresponding ammonium salts, which can be treated with a base, providing a facile method for isolation of secondary amines with high purity. In contrast, tertiary amines are formed with high selectivity by using lower concentration of the catalyst (1 mol %) and polymeric hydrosiloxanes (PMHS) as reducing agent. Reduction with PMHS encapsulates the ruthenium catalyst and organic byproducts to the insoluble silicone resin. The two reaction manifolds are applicable to various secondary amides and are practical in that the procedures provide the desired secondary or tertiary amine as a single product. The product contaminated with only minimal amounts of ruthenium and silicon residues. On the basis of the products and observed side products as well as NMR studies a mechanistic scenario for the reaction is also described.