Search

We carried out the first multi-institutional prospective study on accelerated partial breast irradiation (APBI) via multicatheter interstitial brachytherapy in a shorter period for early breast cancer in Japan.Patient eligibility criteria included positive hormone receptors, tumors ≤ 3 cm and TNM stage pN0M0. After breast-conserving surgery (Japanese cylindrical resection) and histological confirmation of negative surgical margins and the absence of lymph node metastasis, applicator implantation was performed either postoperatively or intraoperatively. High-dose-rate brachytherapy of 36 Gy in 6 fractions was delivered.Forty-six patients from six institutions received this treatment regimen, and the median follow-up time was 60 months (range 57-67 months). The median resected breast tissue volume was 81 cmThis study showed excellent local control and survival results with minimal late sequelae.

We initiated the first multi-institutional prospective study of accelerated partial breast irradiation for early breast cancer in Japan. Our early clinical results showed that the treatment methods were technically reproducible between institutions and showed excellent disease control at a median follow-up of 26 months in our previous report. At present, total 46 patients from six institutions underwent the treatment regimen from October 2009 to December 2011, and the median follow-up time was 60 months (range, 57-67 months). In 46 patients, we experienced one patient who had rib fracture as a late complication. The dose-volume histogram (DVH) result of this patient was analyzed. The D0.01cc, D0.1cc, and D1cc values of the patient were 913, 817, and 664 cGy per fraction, respectively. These values were the highest values in 46 patients. The average D0.01cc, D0.1cc, and D1cc values of the other 45 patients were 546, 500, and 419, respectively, cGy per fraction. From this result, DVH values showing high-dose irradiated volume (D0.01cc, D0.1cc, and D1cc) seem to be a good predictive factor of rib fracture for accelerated partial breast irradiation. However, further investigation is necessary because of the small number of patients investigated.

Background The purpose of this study was to evaluate the efficacy and toxicities of proton beam therapy combined with intra-arterial infusion chemotherapy via superficial temporal and occipital arteries for recurrent oral cavity squamous cell carcinoma (SCC). Methods Between October 2009 and June 2013, 46 patients with recurrent oral cavity SCC were treated by proton beam therapy combined with intra-arterial infusion chemotherapy of cisplatin (CDDP) and docetaxel. Treatment consisted of proton beam therapy (28.6–74.8 GyE in 13–34 fractions) and intra-arterial infusion chemotherapy (CDDP, 30–50 mg/body/week; docetaxel, 5–25 mg/body/week). Results One-year and 2-year overall survival (OS) rates were 65% and 46%, respectively. One-year and 2-year local control rates were 81% and 70%, respectively. Conclusion These findings suggest that proton beam therapy combined with intra-arterial infusion chemotherapy could be applied effectively and safely for patients with recurrent oral cavity SCC. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

The effect of proton beam therapy (PBT) on various cancers is controversial. We aimed to evaluate the efficacy and safety of PBT with alternating chemoradiotherapy (ACRT) for patients with stage I–III esophageal cancer. Two cycles of systemic chemotherapy with a continuous infusion of 5‐fluorouracil (5‐FU) on days 1–5 and a 5h infusion of nedaplatin (NDP) on day 6 were accompanied by thoracic irradiation using X‐ray therapy and PBT. During the first half of the treatment, X‐rays were delivered to the prophylactic area. During the second half of the treatment, proton beams were used to irradiate the involved field. To reduce the dose of cardiac irradiation, proton beams were delivered with posterior and posterior oblique angles. Between January 2009 and December 2012, 47 patients were enrolled in this study. The median follow‐up duration was 29 months for all patients and 40 months for survivors. The 3 year overall survival rate, progression‐free survival rate, and local control rate were 59.2%, 56.3%, and 69.8%, respectively. With respect to grade 3–4 late toxicities, there were no pleural or pericardial effusions, but two patients (4.3%) had esophageal stenosis, one patient (2.1%) had fistula, and two patients (4.3%) developed radiation pneumonitis. PBT with ACRT might have the potential to reduce the risk of cardiac damage and might become one of the primary methods of esophageal cancer treatment.

Background. In an aging society, increasing number of older patients are diagnosed with esophageal cancer. The purpose of this study was to assess the clinical efficacy and safety of proton beam therapy for older patients with esophageal cancer. Patients and methods. Older patients (age: ≥ 65 years) newly diagnosed with esophageal cancer between January 2009 and June 2013 were enrolled in this study. All patients underwent either proton beam therapy alone or proton beam therapy with initial X-ray irradiation. Toxicities were evaluated using the Common Terminology Criteria for Adverse Events version 4.0. Results. Twenty patients were eligible for this study and all completed the treatment. The median age was 78 years (range: 65–89 years) and the median follow-up time was 26.5 months (range: 6–62 months). Seven patients had lymph node metastases and 10 had stage II/III cancer. The median dose of proton beam therapy was 72.6 Gy relative biological dose effectiveness (RBE) (range: 66–74.8 Gy [RBE]) for proton beam therapy alone and 33 Gy (RBE) (range: 30.8–39.6 Gy [RBE]; total dose range: 66.8–75.6 Gy [RBE]) for proton beam therapy with initial X-ray irradiation. The 2-year overall survival rate was 81.8% (95% confidence interval [CI]: 62.4%–100%), and the 2-year local control rate was 89.4% (95% CI: 75.5%–100%). Grade 2 or 3 toxicities occurred in some cases; however, no grade 4 or 5 toxicity was observed. Conclusions. High-dose (66–75.6 Gy [RBE]) proton beam therapy without chemotherapy was an efficacious and safe treatment for older patients with esophageal cancer.

A Japanese prospective multi-institutional feasibility study on accelerated partial breast irradiation using interstitial brachytherapy was performed. The first clinical results were reported with a median follow-up of 26 months. Forty-six female breast cancer patients with positive hormone receptors and tumors ≤3 cm, pN0M0, completed the protocol treatment. After breast-conserving surgery and histological confirmation of negative surgical margins and pN0, brachytherapy applicators were implanted either postoperatively (n = 45) or intraoperatively (n = 1). High-dose-rate brachytherapy of 36 Gy/6 fractions was delivered. All clinical data were prospectively collected using case report forms and the Common Terminology Criteria for Adverse Events ver.3.0. At the median follow-up of 26 months, no breast cancer recurrence of any type was observed. Sequelae ≥G2 were dermatitis (G2, 7 %), fibrosis (G2, 11 %; G3, 4 %), fracture (G2, 2 %), pain (G2, 7 %; G3, 2 %), and soft tissue necrosis (G2, 6 %). Cosmetic outcomes evaluated by excellent/good scores were 100 % at pre-therapy (n = 46), 94 % at 12 months (n = 46), and 81 % at 24 months (n = 36), respectively. Disease control and sequelae were satisfactory due to the strict eligibility and protocol-defined treatment parameters. The cosmetic outcomes were comparable to those of previous Japanese breast-conserving therapy series.

We conducted a preliminary retrospective evaluation of the efficacy and toxicity of proton-beam therapy (pbt) for stage iii non-small-cell lung cancer. Between January 2009 and August 2013, 27 patients (26 men, 1 woman) with stage iii non-small-cell lung cancer underwent pbt. The relative biologic effectiveness value of the proton beam was defined as 1.1. The beam energy and spread-out Bragg peak were fine-tuned such that the 90% isodose volume of the prescribed dose encompassed the planning target volume. Of the 27 patients, 11 underwent neoadjuvant chemotherapy. Cumulative survival curves were calculated using the Kaplan&ndash, Meier method. Treatment toxicities were evaluated using version 4 of the Common Terminology Criteria for Adverse Events. Median age of the patients was 72 years (range: 57&ndash, 91 years), and median follow-up was 15.4 months (range: 7.8&ndash, 36.9 months). Clinical stage was iiia in 14 patients (52%) and iiib in 13 (48%). The median dose of pbt was 77 GyE (range: 66&ndash, 86.4 GyE). The overall survival rate in the cohort was 92.3% at 1 year and 51.1% at 2 years. Locoregional failure occurred in 7 patients, and distant metastasis, in 10. In 2 patients, initial failure was both locoregional and distant. The 1-year and 2-year rates of local control were 68.1% and 36.4% respectively. The 1-year and 2-year rates of progression-free survival were 39.9% and 21.4% respectively. Two patients experienced grade 3 pneumonitis. For patients with stage iii non-small-cell lung cancer, pbt can be an effective and safe treatment option.

Background. Evidence has suggested that radiation therapy with a lower dose per fraction may be a reasonable option for the treatment of centrally located non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the safety and efficacy of two proton beam therapy (PBT) protocols for stage I NSCLC and to determine prognostic factors.Material and methods. This study included patients clinically diagnosed with stage I NSCLC. Based on the location of the tumor, one of the two PBT protocols was administered. Patients with peripherally located tumors were given 66 Gy relative biological dose effectiveness (RBE) over 10 fractions (Protocol A) while patients with centrally located tumors were given 80 Gy (RBE) over 25 fractions (Protocol B).Results. Between January 2009 and May 2012, 56 eligible patients were enrolled (protocol A: 32 patients; protocol B: 24 patients). The three-year overall survival (OS), progression-free survival (PFS), and local control (LC) rates were 81.3% [95% confidence interval (CI) 75.9–86.7%], 73.4% (95% CI 67.2–79.6%), and 96.0% (95% CI 93.2–98.8%), respectively. There were no significant differences in outcomes between the two protocols. Late grade 2 and 3 pulmonary toxicities were observed in nine patients (13.4%) and one patient (1.5%), respectively; no grade 4 or 5 toxicities were observed. Sex, age, performance status, T-stage, operability, and tumor pathology were not associated with OS and PFS. Only maximum standardized uptake value (SUVmax; < 5 vs. ≥ 5) was identified as a significant prognostic factor for OS and PFS.Conclusion. Both high-dose PBT protocols achieved high LC rates with tolerable toxicities in stage I NSCLC patients, and SUVmax was a significant prognostic factor.

We conducted a multi-institutional prospective study on accelerated partial breast irradiation (APBI) using interstitial brachytherapy. The clinical results over a minimum follow-up period of 30 months are presented here. Forty-six patients with breast cancer were treated with breast-conserving surgery and postoperative APBI. After confirmation of negative surgical margins and negative lymph nodes, a high-dose-rate brachytherapy protocol of 36 Gy/6 fractions was carried out. All clinical data were prospectively collected using the Common Terminology Criteria for Adverse Events ver. 3.0. No recurrence was observed. Cumulative rates of grade 2 or higher late sequelae were 25% for fibrosis, 2% for fractures, 9% for pain, and 9% for soft tissue necrosis. Rates of excellent or good cosmetic results as assessed by the physician and patient were 93 and 89% at the 12-month follow-up and 76 and 74% at the 30-month follow-up, respectively. Large volumes of resected tissue in small breasts were associated with fibrosis of grade 2 or higher. APBI in Japanese women provides satisfactory clinical results except for cosmetic outcomes. There is some difficulty with the assessment of fibrosis and cosmetic outcomes, especially in patients with small breasts. UMIN000001677.

Although the outcome of surgery for locally advanced pancreatic cancer remains poor, it is improving, with 5-year survival up to about 10% in Japan. The preliminary results of our multi-institutional randomized controlled trial revealed better survival after surgery than after radiochemotherapy. We report the final results of this study after 5 years of follow-up. Patients with preoperative findings of pancreatic cancer invading the pancreatic capsule without involvement of the superior mesenteric or common hepatic arteries, or distant metastasis, were included in this randomized controlled trial, with their consent. If the laparotomy findings were consistent with these criteria, the patient was randomized to a surgery group or a radiochemotherapy group (5-fluorouracil 200 mg/m2/day and 5040 Gy radiotherapy). We compared the mean survival time, 3-and 5-year survival rates, and hazard ratio. The surgery and radiochemotherapy groups comprised 20 and 22 patients, respectively. Patients were followed up for 5 years or longer, or until an event occurred to preclude this. The surgery group had significantly better survival than the radiochemotherapy group (P < 0.03). Surgery increased the survival time and 3-year survival rate by an average of 11.8 months and 20%, respectively, and it halved the instantaneous mortality (hazard) rate. Locally invasive pancreatic cancer without distant metastases or major arterial invasion is treated most effectively by surgical resection.

Background In Japan, breast-conserving surgery with closed cavity has generally been performed for breast cancer patients, and accelerated partial breast irradiation (APBI) is considered difficult because Asian females generally have smaller breast sizes than Western females. Therefore, common identification of target and treatment plan method in APBI is required. A prospective multicenter study was conducted in Japan to determine institutional compliance with APBI using high-dose-rate interstitial brachytherapy (ISBT) designed for Japanese female patients. Methods For this study, 46 patients were recruited at eight institutions from January 2009 to December 2011. The reproducibility of the ISBT–APBI plan was evaluated using three criteria: (1) minimum clinical target volume dose with a clip dose ≥ 6 Gy/fraction, (2) irradiated volume constraint of 40-150 cm3, and (3) uniformity of dose distribution, expressed as the dose non-uniformity ratio (DNR, V150/V100)

The purpose of this study was to evaluate the efficacy and toxicities of proton beam therapy combined with intra-arterial infusion chemotherapy via superficial temporal and occipital arteries for recurrent oral cavity squamous cell carcinoma (SCC).Between October 2009 and June 2013, 46 patients with recurrent oral cavity SCC were treated by proton beam therapy combined with intra-arterial infusion chemotherapy of cisplatin (CDDP) and docetaxel. Treatment consisted of proton beam therapy (28.6-74.8 GyE in 13-34 fractions) and intra-arterial infusion chemotherapy (CDDP, 30-50 mg/body/week; docetaxel, 5-25 mg/body/week).One-year and 2-year overall survival (OS) rates were 65% and 46%, respectively. One-year and 2-year local control rates were 81% and 70%, respectively.These findings suggest that proton beam therapy combined with intra-arterial infusion chemotherapy could be applied effectively and safely for patients with recurrent oral cavity SCC. © 2016 Wiley Periodicals, Inc. Head Neck 38:1145-1151, 2016.

OBJECTIVE This study aimed to evaluate the efficacy and toxicity of proton beam therapy combined with cisplatin intra-arterial infusion via a superficial temporal artery as treatment for maxillary sinus carcinoma. METHODS Twenty-six patients with confirmed maxillary sinus carcinoma were enrolled in this study from May 2009 to April 2011. Patients underwent proton beam therapy and intra-arterial infusion chemotherapy with cisplatin. RESULTS The median total dose was 70.4 GyE per 32 fractions, and the median dose of cisplatin was 300 mg/body for six cycles of intra-arterial infusion. The 3-year overall survival rate was 58% for all patients (n = 26), 58% for patients with stage T4 disease (n = 12), 57% for patients with

Background To evaluate the feasibility and efficacy of docetaxel consolidation therapy after concurrent chemoradiotherapy for unresectable stage III non–small cell lung cancer (NSCLC). Patients and Methods The eligibility criteria included unresectable stage III NSCLC, no previous treatment, age between 20 and 74 years, and performance status 0 or 1. Treatment consisted of cisplatin (80 mg/m 2 on days 1, 29, and 57), vinorelbine (20 mg/m 2 on days 1, 8, 29, 36, 57, and 64), and thoracic radiotherapy (TRT) (60 Gy/30 fractions over 6 weeks starting on day 2), followed by consolidation docetaxel (60 mg/m 2 every 3 to 4 weeks for three cycles). Results Of 97 patients who were enrolled in this study between 2001 and 2003, 93 (76 males and 17 females with a median age of 60) could be evaluated. Chemoradiotherapy was well tolerated; three cycles of chemotherapy and 60 Gy of TRT were administered in 80 (86%) and 87 (94%) patients, respectively. Grade 3 or 4 neutropenia, esophagitis, and pneumonitis developed in 62, 11, and 3 patients, respectively. Docetaxel consolidation was administered in 59 (63%) patients, but three cycles were completed in only 34 (37%) patients. The most common reason for discontinuation was pneumonitis, which developed in 14 (24%) of the 59 patients. During consolidation therapy, grade 3 or 4 neutropenia, esophagitis, and pneumonitis developed in 51, 2, and 4 patients, respectively. A total of four patients died of pneumonitis. We calculated a V 20 (the percent volume of the normal lung receiving 20 Gy or more) on a dose–volume histogram in 25 patients. Of these, five patients developed grade 3 or more severe radiation pneumonitis. A median V 20 for these five patients was 35% (range, 26–40%), whereas the median V 20 for the remaining 20 patients was 30% (range, 17–35%) ( p = 0.035 by a Mann–Whitney test). The response rate was 81.7% (95% confidence interval [CI], 72.7–88.0%), with 5 complete and 71 partial responses. The median progression-free survival was 12.8 (CI, 10.2–15.4) months, and median survival was 30.4 (CI, 24.5–36.3) months. The 1-, 2-, and 3-year survival rates were 80.7, 60.2, and 42.6%, respectively. Conclusion This regimen produced promising overall survival in patients with stage III NSCLC, but the vast majority of patients could not continue with the docetaxel consolidation because of toxicity.

下垂体転移による尿崩症を合併した肺腺癌の一例を報告する.症例は63歳の男性で, 1日4-5lの多飲.多尿を主訴に受診した.尿比重1.003, 尿浸透圧102mOsm/kg, 血清浸透圧298mOsm/kg, 血清ADH0.7pg/mlで, 飲水制限試験にて血清浸透圧313mOsm/kg, 尿浸透圧137mOsm/kgで, 尿浸透圧/血清浸透圧は1以下のままでかつADH値も0.8pg/mlと無反応であることより尿崩症と診断した.下垂体前葉ホルモン値には異常を認めなかった.血清CEA高値で, 胸部異常影を認め精査にて肺腺癌と診断した.頭部単純X線ではトルコ鞍底・鞍背の骨破壊像を認めた.頭部MRI (T1強調像) では下垂体後葉に腫瘤影と骨破壊像を認め, 同部の高信号の消失も認めた.肺腺癌の下垂体転移と診断し, トルコ鞍部に放射線照射後, シスプラチンとイリノテカンの抗癌剤治療を施行したが, 症状の改善および腫瘍の縮小は認められなかった.

Background We examined the efficacy and toxicity of proton beam therapy (PBT) for treating advanced cholangiocarcinoma. Methods The clinical data and outcomes of 28 cholangiocarcinoma patients treated with PBT between January 2009 and August 2011 were retrospectively examined. The Kaplan–Meier method was used to estimate overall survival (OS), progression-free survival (PFS), and local control (LC) rates, and the log-rank test to analyze the effects of different clinical and treatment variables on survival. Acute and late toxicities were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Results The median age of the 17 male and 11 female patients was 71 years (range, 41 to 84 years; intrahepatic/peripheral cholangiocarcinoma, n = 6; hilar cholangiocarcinoma/Klatskin tumor, n = 6; distal extrahepatic cholangiocarcinoma, n = 3; gallbladder cancer, n = 3; local or lymph node recurrence, n = 10; size, 20–175 mm; median 52 mm). The median radiation dose was 68.2 Gy (relative biological effectiveness [RBE]) (range, 50.6 to 80 Gy (RBE)), with delivery of fractions of 2.0 to 3.2 Gy (RBE) daily. The median follow-up duration was 12 months (range, 3 to 29 months). Fifteen patients underwent chemotherapy and 8 patients, palliative biliary stent placement prior to PBT. OS, PFS, and LC rates at 1 year were 49.0%, 29.5%, and 67.7%, respectively. LC was achieved in 6 patients, and was better in patients administered a biologically equivalent dose of 10 (BED10) > 70 Gy compared to those administered 70 Gy. Gastrointestinal toxicities, especially those of the duodenum, are dose-limiting toxicities associated with PBT, and early metastatic progression remains a treatment obstacle.

Small-field radiotherapy based on a 6-MeV linac and a conventional head mold is investigated as an alternative to radiosurgery with stereotactic frames. The system requires no additional device and allows fractionated treatment. The dose distributions obtained are comparable to those reported with a Gamma Unit. Overall positioning errors are within 2 nun. Using this approach, seven patients with brain tumors who could not have been treated otherwise, underwent fractionated radiotherapy with total accumulated doses ranging from 70 to 108 Gy. The treatment was tolerated well with no acute toxicity or adverse effect encountered during the follow-up period of 8–14 months. All of the patients remained free from disease progression in the treated volumes. Although the follow-up is brief, the preliminary results suggest that this is a simple and inexpensive but effective system for the treatment of small intracranial malignancies.

By comparing the incidence of major radiation injury, we estimated doses clinically equivalent for high-dose-rate (HDR) to conventional low-dose-rate (LDR) intracavitary irradiation in patients with Stages IIb and IIIb cancer of the uterine cervix. We reviewed a total of 300 patients who were treated with external beam therapy to the pelvis (50 Gy in 5 weeks) followed either by low-dose-rate (253 patients) or high-dose-rate (47 patients) intracavitary treatment. The high-dose-rate intracavitary treatment was given 5 Gy per session to point A, 4 fractions in 2 weeks, with a total dose of 20 Gy. The low-dose-rate treatment was given with one or two application(s) delivering 11-52 Gy to the point A. The local control rates were similar in both groups. The incidence of major radiation injury requiring surgical intervention were 5.1% (13/253) and 4.3% (2/47) for low-dose-rate and high-dose-rate groups, respectively. The 4.3% incidence corresponded to 29.8 Gy with low-dose-rate irradiation, thus, it was concluded that the clinically equivalent dose for high-dose-rate irradiation was approximately 2/3 (20/29.8) of the dose used in low-dose-rate therapy.

It is unlikely that adjuvant chemoradiotherapy applied to the pancreatic bed alone significantly improves the survival of patients with resectable pancreatic cancer. The aim of the present study was to determine whether prophylactic hepatic irradiation (PHI) improved patient outcome after the curative resection of pancreatic cancer. The study population was comprised of 34 patients (PHI group) who were administered PHI after curative resection of pancreatic cancer between September 1994 and December 2003. The whole liver was irradiated with a total dose of 19.8–22.0 Gy under continuous infusion of 5-fluorouracil. The cumulative rate of liver metastasis and the survival outcomes of the PHI group were compared with those of 31 patients without PHI (non-PHI group) who underwent curative resection of pancreatic cancer. The planned PHI was completed for 32 of the 34 patients. Two patients developed complications that might have been PHI-related. One developed liver abscesses which were successfully managed by percutaneous drainage. The other died of liver failure without recurrence 11 months after the operation. The cumulative incidence of liver metastasis was significantly lower for the PHI group than the non-PHI group (P = 0.0455). Patients in the PHI group also survived significantly longer compared to those in the non-PHI group (P = 0.0002). The present findings suggest that PHI is well tolerated and is a potentially effective treatment strategy after curative resection of pancreatic cancer, thereby providing the basis for a randomized controlled trial.

PURPOSE: To evaluate the efficacy and toxicity of high-dose thoracic radiotherapy (TRT) alternating with chemotherapy (CH) for unresectable stage III non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Forty-one patients received TRT with 1.5 Gy twice daily, 5 days a week, on weeks 1, 2, 5, 6, and 9, up to a total dose of 66 to 72 Gy, alternating with cisplatin 80 mg/m2 on day 1 and vindesine 3 mg/m2 on days 1 and 8, repeated every 4 weeks, for two or three courses beginning on week 3. RESULTS: The median (range) total dose of TRT and number of CH courses were 72 Gy (16.5 to 72 Gy) and three (zero to three), respectively. Delay in TRT ≥ 5 days was observed in 24 (75%) of 32 patients who completed the projected treatment, due to leukopenia in 12, esophagitis in seven, infection in two, and other causes in three patients. Partial responses were obtained in 36 patients (88%). The median survival time and 3- and 5-year survival rates were 18.4 months, 24%, and 10%, respectively. Grade 3 or 4 leukopenia and esophagitis developed in 32 and seven patients, respectively. Grade 3 or 4 late esophageal toxicity developed in two patients. CONCLUSION: Alternating high-dose TRT and CH for stage III NSCLC produced a high response rate with median and long-term survival comparable to prior trials utilizing standard approaches in this population. Acute and late esophageal toxicity was observed and interruption of TRT was required in most of the patients.

A multi-institutional study on simultaneous intraluminal thermobrachytherapy (SITB) for advanced esophageal cancer was conducted in Japan. In this study, brachytherapy was administered by a small radioactive source stepping through a catheter in the esophagus, and hyperthermia was also applied by an endoesophageal coil. However, experimental or clinical findings on the spatial distribution of its antitumor effects around the esophagus are not available. Therefore, we developed an in vitro model of SITB using a high-dose-rate iridium-192 stepping source and two human cancer cell lines (WiDr and A549), and determined the spatial distribution of the antitumor effects. According to this model, the antitumor effects steeply decreased as the source-cell distance increased when cells of both cell lines were irradiated with 5 Gy without heat. When WiDr cells, a more resistant cell line to radiation and heat, were simultaneously irradiated and heated for 30 min at 44 degrees C, the effects decreased much less steeply as the distance increased. For A549 cells, a more sensitive cell line, irradiation with hyperthermia even at 42 degrees C made the decrease in the effects smaller. The largest antitumor effects can be expected at 5 - 10 mm beneath the esophageal mucosa, where the endoesophageal coil can heat tissues most effectively. SITB can induce larger antitumor effects than brachytherapy alone, especially in submucosal disease, which would favor treatment of advanced cancer.

We investigated the clinical usefulness of radiation therapy by external beam irradiation and endobronchial brachytherapy for the treatment of roentogenographically occult lung cancer.From 1995 to 1996, five patients were treated with radiation therapy. We analyzed their treatment outcomes. The follow-up period varied from 3.0 to 3.8 years or until death. External beam radiation (40 Gy/20 fractions/4 weeks) was delivered to the tumor site alone, and not prophylactically given to the mediastinum. Endobronchial brachytherapy using high dose rate iridium (Ir)-192 was concurrently administered principally to a total dose of 18 Gy on the bronchial mucosa in three weekly fractions of 6 Gy each.Complete remission was obtained in all patients. Two patients died of intercurrent diseases at 12 and 21 months without any evidence of recurrence. The disease has been also controlled in the other three cases. With the above doses, three small tumors1 cm were controlled without adverse effect. In two tumors, the dose reference points were set 2-7 mm beneath the mucosa, and larger doses were administered by brachytherapy. An applicator acting as a spacer was not used in these cases. The tumors were controlled, although the irradiated bronchi showed severe stenosis in 6 months following the treatment. However, the patients were asymptomatic and did not need further intervention.External beam irradiation combined with endobronchial brachytherapy was useful for the treatment of roentogenographically occult lung cancer as an alternative to surgery. Further investigation is needed to determine the optimal doses of radiation therapy.

The authors report a case of recurrent thymoma displaying endobronchial polypoid growth. Initially, the patient had invasive thymoma with intracaval growth into the right atrium. He was treated with multimodality therapy consisting of chemotherapy, surgical resection, and radiotherapy (50.4 Gy). Both 3 years and 6 years after the initial treatment, the tumor recurred outside the reconstructed superior vena cava. The patient was treated with repeated radiotherapy (50.4 Gy and 40 Gy), and remission was achieved. Eight years after the first therapy, an endobronchial polypoid lesion was detected in the right upper lobe bronchus and was histologically found to be thymoma. Endobronchial high-dose rate brachytherapy (20 Gy at 3 mm/5 fractions) was carried out for palliation because the recurrent tumor occurred outside of the superior vena cava area, which had been reirradiated. After the treatment, the endobronchial tumor shrunk remarkably in size without adverse effects. No tumor regrowth has been noted after a follow-up of 10 months.

6086 Background: The standard treatment for locally advanced tongue cancer is surgery. However, the patient’s quality of life is lost. As a newly non-operative treatment, we report the efficacy and toxicity of proton beam therapy combined with selective intra-arterial infusion chemotherapy (PBT-IACT) for locally advanced tongue cancer. Methods: Between February 2009 and August 2012, 45 cases of stage III-IV(M0) squamous cell carcinoma of the tongue (28 men and 17 women) were treated by PBT-IACT at Southern TOHOKU Proton Therapy Center. Median age was 58 years (range:24-83 years), and clinical stage III/IVA/IVB were 11/32/2 respectively. In case of surgery, the patients required subtotal or total resection of the tongue. Initially, 2 courses of systemic chemotherapy and prophyractic whole neck irradiation (36Gy/20fr.) were performed. Subsequently, for gross tumor targets, PBT (33Gy/15fr.) and IACT were administered via the superficial temporal artery by continuous infusion of cisplatin with sodium thiosulphate. For PBT, 1 or 2 portals of 210 MeV proton beam were arranged in optimal angles to avoid overdosing the risk organ. Systemic chemotherapy was performed only for age of 70 years or younger. Results: The median follow-up was 27 months (range:8-48 months). Over all survival (OS), disease-free survival (DFS), and local control (LC) rates at 2 years were 88%,78%, 80%, respectively. LC of cervical lymph node metastases at 2 years was 86%. As the early toxic event, grade 3 mucositis (32/45) and blood/bone marrow toxicity (22/45) were observed. Within 6 months after this therapy, mandibular osteomyelitis occurred in 1 case. Conclusions: PBT-IACT appeared to be safe and has a good LC rate for locally advanced tongue cancer. Furthermore, it is not inferior to surgery and can be one of the new effective treatment options for locally advanced tongue cancer.

device was used for both preand post-implant planning. Stranded seeds were created and intraoperatively placed in real time using the INSTANT (tm) device. A total dose of 25 Gy was delivered to the biopsy cavity with 1.0cm margin over the life of the isotope. The patients wore a shielded bra for six weeks after the procedure. Pre-planning utilized ultrasound and CT while post planning utilized CT only at one week. A second CT was performed 6 weeks after the seed implant to verify seed stability. Results: Cosmetic results were excellent with no evidence of needle marks by 6 weeks post procedure. Patient tolerance was exceptional, returning to work within 3 days of the procedure with minimal to no breast discomfort. No acute erythema and no radiation mysositis observed over the first 3 months after the procedure. Conclusions: Permanent Pd seed implantation as boost therapy appears to be safe. It is inexpensive and is well tolerated. A similar technique has been described by Pignol, et al for the sole local mangement of early stage breast cancer and the technique described in this paper could easily by adjusted to provide the sole local management for early stage breast cancer as well.

We treated 154 patients with T1 glottic carcinoma with 6 MeV X rays through 16 cm 2 parallel-opposing open fields on a free set-up delivering a median dose of 67 Gy in 623 weeks. Observed and relative 5-year survival rates for all patients were 87% and 100%, respectively. The local control rate at 5 years was 89%. Of 18 patients who clinically had local recurrence, 17 were salvaged by a secondary treatment. There were no complications requiring medical or surgical attention. A tendency toward increasing local control rates with increasing total doses was observed in the range between 57.5 Gy and 72.5. No significant correlation was found between local control rates and field size, daily dose, or the technique used. A tendency toward a lower local control rate was noted for patients whose anterior commissures were grossly involved; however, it is not known if this could be attributed to the use of 6 MeV X rays. The results are comparable to those obtained with 60 Co as reported in the literature. It is concluded that 6 MeV X rays on a free set-up delivering 65–70 Gy in 623–7 weeks can be used satisfactorily for the treatment of early glottic carcinoma.

Treatment results of 244 patients with stage I-II cancer of the mobile tongue were analyzed according to the modalities employed (implantation, surgery, cryosurgery and intraoral irradiation). Overall local control rates at three years were 90 ± 3% for implant, 89 ± 7 % for cryosurgery, and 84 ± 9 % for surgery. Local control rates in stage II patients treated with intraoral electron irradiation, however, were only 50 ± 13%. Five-year survival rates were 72 ± 3% with no significant differences observed in patients with either stage I or stage II regardless of treatment modality. Sixty percent (29/48) of the patients with local recurrences were salvaged by the second treatment. Since the local control and survival achieved by these modalities were similar, with the exception of patients with stage II treated by intraoral electron irradiation, we recommend interstitial implantation with iridium, intraoral electron irradiation or surgery for patients with T1 tumors, and iridium implantation or surgery for patients with T2 tumors. For those with superficial lesions measuring 5 mm or less in thickness, cryosurgery is being offered as an alternative. The patient can choose the treatment modality taking into account his/her age, sex and profession.

Nineteen patients with soft tissue sarcoma were treated by a combination modality of hyperthermia and radiation or chemotherapy. There were 26 treatment sites. The size of the tumours ranged from 2.5 x 2 cm to 24 x 26 cm. Hyperthermic treatments were given twice a week, for a total of five to 14 sessions. Twenty-one tumours were treated by hyperthermia combined with radiotherapy, 2 Gy daily, five times a week, for a total of 40-78 Gy. Three tumours were treated by hyperthermia and arterial infusion of adriamycin, 100-120 mg in five or six treatments. For the superficial tumours the complete response rate was 40 per cent, and for the deep-seated tumours 6.2 per cent. Among the 12 tumours with no response, nine in which the treatment was evaluated as effective histologically (necrosis of the tumour) and by X-ray CT findings (development of a prominent hypodensity area) were included. Six cases were studied to correlate the X-ray CT findings, angiography and histological findings before and after hyperthermic treatment. The data were also used to interpret the thermal curve. The increased hypodensity area was roughly proportional to the development of necrosis, but there was one case in which hypodensity was not correlated with the necrosis. On the contrary, even in the contrast-enhanced area around the tumour in which the presence of residual tumour was strongly suspected clinically, no tumour cells were visualized. Clinical evaluation of the effect by size of the tumour can be supplemented by CT findings and histology, but should be cautiously adopted.

Eighty-four patients with previously untreated invasive carcinoma of the uterine cervix were treated by high-dose-rate intracavitary irradiation using a remotely controlled afterloading system (Ralstron) with or without external irradiation at the National Cancer Center Hospital, Tokyo, between 1977 and 1981. Survival rates and local control rates were comparable to those for 372 patients treated by low-dose-rate intracavitary irradiation with or without external irradiation from 1972 to 1981 at the hospital. The incidence of major complications was 5.1 and 2.4% for the patients treated by low-dose-rate intracavitary irradiation and by high-dose-rate irradiation, respectively. The results are comparable to those reported by other institutions. We have abandoned the conventional low-dose-rate intracavitary irradiation with the impression that the high-dose-rate remotely controlled afterloading system is a good alternative to the conventional one.