Ryuta Koike

A prospective clinical trial of tumor hypoxia imaging with 18F-fluoromisonidazole positron emission tomography and computed tomography (F-MISO PET/CT) before and during radiation therapy

To visualize intratumoral hypoxic areas and their reoxygenation before and during fractionated radiation therapy (RT), 18F-fluoromisonidazole positron emission tomography and computed tomography (F-MISO PET/CT) were performed. A total of 10 patients, consisting of four with head and neck cancers, four with gastrointestinal cancers, one with lung cancer, and one with uterine cancer, were included. F-MISO PET/CT was performed twice, before RT and during fractionated RT of approximately 20 Gy/10 fractions, for eight of the 10 patients. F-MISO maximum standardized uptake values (SUVmax) of normal muscles and tumors were measured. The tumor-to-muscle (T/M) ratios of F-MISO SUVmax were also calculated. Mean SUVmax ± standard deviation (SD) of normal muscles was 1.25 ± 0.17, and SUVmax above the mean + 2 SD (≥1.60 SUV) was regarded as a hypoxic area. Nine of the 10 tumors had an F-MISO SUVmax of ≥1.60. All eight tumors examined twice showed a decrease in the SUVmax, T/M ratio, or percentage of hypoxic volume (F-MISO ≥1.60) at approximately 20 Gy, indicating reoxygenation. In conclusion, accumulation of F-MISO of ≥1.60 SUV was regarded as an intratumoral hypoxic area in our F-MISO PET/CT system. Most human tumors (90%) in this small series had hypoxic areas before RT, although hypoxic volume was minimal (0.0–0.3%) for four of the 10 tumors. In addition, reoxygenation was observed in most tumors at two weeks of fractionated RT.

A randomized phase II study of cisplatin/5-FU concurrent chemoradiotherapy for esophageal cancer: Short-term infusion versus protracted infusion chemotherapy (KROSG0101/JROSG021)

PURPOSE A randomized phase II study was conducted to compare the toxicity and efficacy of combining short-term chemotherapy (CT) or protracted CT with radiotherapy (RT) for esophageal cancer. MATERIALS AND METHODS Eligible patients were <75 years and with performance status (PS) of 0-2, and had stages II-IVA esophageal cancer. Two cycles of cisplatin 70 mg/m(2) for 1 day and 5FU 700 mg/m(2) for 5 days (arm A) or cisplatin 7 mg/m(2) for 10 days and 5FU 250 mg/m(2) for 14 days (arm B) were given with RT of 60Gy/30 fractions/7 weeks (1-week split). RESULTS Of 91 patients enrolled, 46 were randomized to arm A and 45 to arm B. Two cycles of CT were given concurrently with RT for 89% in arm A and for 71% in arm B with significant difference (P=.031). The 2- and 5-year overall survival rates for arm A were 46% and 35%, while those for arm B were 44% and 24%, respectively, without significant difference. The 2- and 5-year progression-free survival rates for arm A were 30% and 30%, while those for arm B were 29% and 12%, respectively. CONCLUSIONS Protracted infusion CT with RT provides no advantage over standard short-term infusion CT with RT for esophageal cancer.

Long-term follow-up of a randomized phase II study of Cisplatin/5-FU concurrent chemoradiotherapy for esophageal cancer (KROSG0101/JROSG021)

OBJECTIVE Long-term survival and late toxicities of a randomized Phase II study of chemoradiotherapy for esophageal cancer were analyzed. METHODS Eligible patients were <75 years old and performance status 0-2, and had Stages II-IVA esophageal cancer. For arm A (short-term infusion), cisplatin 70 mg/m(2) Days 1 and 29 and 5-fluorouracil 700 mg/m(2) Days 1-5 and 29-33 were given concurrently with radiotherapy of 60 Gy/30 fr/7 weeks (1 week split). For arm B (protracted infusion), cisplatin 7 mg/m(2) Days 1-5, 8-12, 29-33 and 36-40, and 5-fluorouracil 250 mg/m(2) Days 1-14 and 29-42 were given with the same radiotherapy. Two cycles of consolidation cisplatin/5-fluorouracil chemotherapy were given to both arms. RESULTS Between 2001 and 2006, 91 patients were enrolled; 46 were randomized to arm A, and 45 to arm B. The 2- and 5-year overall survival rates for arm A were 46 and 35% (95% confidence interval: 22-48%), while those for arm B were 44 and 22% (11-35%), respectively. Excluding four patients with early death, seven (17%) patients in arm A and eight (18%) in arm B showed late toxicities of Grade 3 or more. Most of the toxicities were cardiac or pleural toxicities. Patients with severe late toxicities often had coexistent hypothyroidism. There were three patients with a secondary malignancy possibly related to treatment. CONCLUSIONS Low-dose protracted infusion chemotherapy with radiotherapy is not superior to full-dose short-term infusion chemotherapy with radiotherapy for esophageal cancer. Late toxicities, including cardiac and pleural toxicities, hypothyroidism and secondary malignancy, should be carefully monitored.

Treatment outcomes and dose-volume histogram analysis of simultaneous integrated boost method for malignant gliomas using intensity-modulated radiotherapy

BackgroundThe aim of this article is to report the treatment outcomes, toxicities, and dosimetric feasibility of our simultaneous-boost intensity-modulated radiotherapy (SIB-IMRT) protocol.MethodsThirteen patients with malignant gliomas treated between December 2000 and September 2004 were enrolled in this study. Two planning target volumes (PTVs) were defined in the present study. Our IMRT regimen delivered 70 Gy/28 fractions (fr)/daily; 2.5 Gy to the gross tumor volume (GTV) with a 0.5-cm margin, defined as the PTV-G, and 56 Gy/28 fr/daily, with 2.0 Gy to the surrounding edema, defined as the planning target volume annulus (PTV-a). Eleven of the 13 patients received one or two courses of nimustine hydrochloride (ACNU) (100 mg/m2) and vincristine (1.2 mg/body) and interferon-β (3 × 106 units) three times weekly during the period of radiotherapy. Adjuvant chemotherapy, ACNU (100 mg/m2) and vincristine (1.2 mg/body), was repeated every 6 weeks and interferon-β was repeated every 2 weeks. The treatment outcomes, toxicity, and dosimetric feasibility were assessed.ResultsAll the patients experienced tumor recurrence. The median progression-free survival times for patients with grade III tumors and glioblastome were 7.5 and 8.0 months, respectively. The 1-year and 2-year overall survival rates for all the patients were 77% and 31%, respectively. Four patients experienced acute grade 1/2 toxicities during the treatment. No late toxicity related to radiotherapy has been seen. Analyses with dose-volume histograms confirmed excellent conformity of dose distributions in the two target volumes, PTV-G and PTV-a, with the sparing of organs at risk.ConclusionOur IMRT regimen did not prevent tumor progression. However, the ability of IMRT to deliver highly conformative doses to two contiguous targets, GTV and the surrounding edema, justifies its application to malignant gliomas.

A Two-step Intensity-modulated Radiation Therapy Method for Nasopharyngeal Cancer: The Kinki University Experience

OBJECTIVE The aim of this study was to analyze the clinical results of our adaptive radiation therapy scheme of a two-step intensity-modulated radiotherapy (IMRT) method for nasopharyngeal cancer (NPC) at Kinki University Hospital. METHODS Between 2000 and 2007, 35 patients with Stage I-IVB NPC treated by IMRT were included. For all patients, treatment-planning computed tomography was done twice before and during IMRT to a total dose of 60-70 Gy/28-35 fractions (median 68 Gy). Chemotherapy (cisplatin 80 mg/m(2)/3 weeks x 1-3 courses) was given concurrently with IMRT for 31 patients. RESULTS The 3- and 5-year overall survival rates for the 31 patients treated with concurrent chemotherapy were 88% and 83%, respectively. The 3- and 5-year loco-regional control rates for the 31 patients were 93% and 87%, respectively. Planning target volume delineation for the primary site or involved nodes was insufficient for three early cases, resulting in marginal recurrence in the three patients (9%). Except for one patient with early death, xerostomia scores at 1-2 years were: Grade 0, 11; Grade 1, 17; Grade 2, 5; Grade 3, 1. CONCLUSIONS Excellent overall survival and loco-regional control rates were obtained by a two-step IMRT method with concurrent chemotherapy for NPC, although marginal recurrence was noted in some early cases.

Concurrent chemoradiotherapy for esophageal cancer with malignant fistula.

BACKGROUND We reviewed clinical results of chemoradiotherapy (CRT) in the treatment of patients with advanced esophageal cancer with fistulae that developed before or during CRT. METHODS AND MATERIALS The study group included 16 patients with fistulous esophageal cancer treated by means of CRT between 1999 and 2006. Nine patients had fistulae before CRT, whereas 7 developed fistulae during CRT. The group included 12 men and four women with a median age of 55 years (range, 37-77 years). There were 9 patients with Stage III disease and 7 with Stage IV disease. All tumors were squamous cell carcinomas. Two courses of concurrent chemotherapy were combined with radiation therapy; 60 Gy/30 fractions/7 weeks (1-week split). For 15 patients, low-dose protracted chemotherapy with 5-fluorouracil (250-300 mg/m(2) x 14 days) and cisplatin (7 mg/m(2) x 10 days) was administered, whereas full-dose cisplatin and 5-fluorouracil were administered to the remaining patient. RESULTS The planned dose of 60 Gy was delivered to 11 patients (69%), whereas radiation therapy was terminated early in 5 patients (40-58 Gy) because of acute toxicities, including two treatment-related deaths. Disappearance of fistulae was noted during or after CRT in 7 patients (44%). All three esophagomediastinal fistulae were closed, but only four of 13 esophagorespiratory fistulae were closed by CRT. For patients with Stage III, 1- and 2-year survival rates were 33% and 22%, respectively. Median survival time was 8.5 months. CONCLUSION Despite significant toxicity, concurrent CRT appears effective at closing esophageal malignant fistulae.

Definitive Radiation Therapy for Moderately Advanced Laryngeal Cancer: Effects of Accelerated Hyperfractionation

OBJECTIVE The purpose of this retrospective study was to analyze the results of accelerated hyperfractionation for patients with moderately advanced (T2 and T3) laryngeal cancer. METHODS Between 1998 and 2007, 9 supraglottic carcinomas (6 T2N0M0, 2 T2N2M0, 1 T3N0M0), 30 glottic carcinomas (25 T2N0M0, 5 T3N0M0), and 1 T2N0M0 subglottic carcinoma were treated with definitive radiotherapy using accelerated hyperfractionation without concurrent chemotherapy. The dose-fractionation for 35 patients was 72.8 Gy/56 fractions/5.6 weeks, and that for four patients treated between 1998 and 2001 was 72 Gy/60 fractions/6 weeks. One patient who had been treated with steroid therapy for systemic lupus erythematosus was treated by 67.8 Gy/44 fractions/4.4 weeks. RESULTS The local control and overall survival probabilities at 5 years for supraglottic carcinomas were 75% and 86%, respectively. Those for glottic carcinomas were 80% and 92%, respectively. The 5-year local control probabilities for T2 and T3 tumors were 85% and 56%, respectively. This excellent local control rate especially for T2 laryngeal carcinomas may be attributable to the effect of accelerated hyperfractionation. No late toxicities of grade 2 or more was noted among the 39 patients treated with 72.8 Gy/56 fractions or 72 Gy/60 fractions. CONCLUSION Accelerated hyperfractionation of 72.8 Gy/56 fractions/5.6 weeks using 1.3 Gy/fraction seems a safe and effective dose-fractionation for patients with moderately advanced laryngeal carcinomas.

Randomized clinical trial of postoperative strontium-90 radiation therapy for pterygia: treatment using 30 Gy/3 fractions vs. 40 Gy/4 fractions.

Background and Purpose:Postoperative adjuvant treatment with strontium-90 radiation therapy (RT) is a proven technique for reducing the recurrence of pterygium. This randomized trial was conducted to evaluate whether a total dose of 40 Gy provides a better local control rate than a total dose of 30 Gy for surgically resected pterygia.Patients and Methods:A single institutional randomized trial was conducted. Between 1999 and 2003, 74 pterygia in 71 patients were randomly allocated to 30 Gy/3 fractions/15 days (arm A) or to 40 Gy/4 fractions/22 days (arm B). Only primary pterygia for which RT could be started within 3 days of surgical resection were included. Postoperative RT was given by a strontium-90 eye applicator, and a dose of 10 Gy per fraction was delivered in weekly fractions (day 1, 8, 15, 22).Results:Of the 74 pterygia treated, 73 in 70 patients were analyzed. Of the 73 pterygia, 41 were allocated to arm A, and the remaining 32 to arm B. The 2-year local control rates for arm A and arm B were 85% and 75%, respectively, without significant difference. No serious acute and late complications were noted in either arm.Conclusion:Our new standard fractionation for postoperative RT for pterygia is 30 Gy/3 fractions.Ziel:Die postoperative adjuvante Behandlung mit Strontium-90-Strahlentherapie ist eine anerkannte Methode, um das Wiederauftreten von Pterygien zu vermeiden. Anhand der vorliegenden randomisierten Studie sollte untersucht werden, ob bei operativ entferntem Ptergium eine Dosis von 40 Gy eine bessere Kontrollrate als eine Dosis von 30 Gy bietet.Patienten und Methodik:Eine einzelinstitutionelle, randomisierte Untersuchung wurde durchgeführt. Zwischen 1999 und 2003 wurden 74 Pterygien bei 71 Patienten stichprobenartig entweder mit 30 Gy/3 Fraktionen/15 Tage (Gruppe A) oder 40 Gy/ 4 Fraktionen/22 Tage (Gruppe B) behandelt. Es wurden nur primäre Pterygien berücksichtigt, bei denen innerhalb von 3 Tagen nach der operativen Entfernung mit der RT begonnen werden konnte. Die postoperative RT wurde mit einem Strontium-90-Augenapplikator durchgeführt, und zwar in Dosen von 10 Gy pro wöchentlicher Teilbehandlung (Tag 1, 8, 15, 22).Ergebnisse:Von den 74 behandelten Pterygien wurden 73 von 70 Patienten analysiert. Von diesen 73 gehörten 41 zu Gruppe A, die übrigen 32 zu Gruppe B. Die 2-Jahres-Kontrollraten für Gruppe A und Gruppe B lagen bei 85% und 75% ohne signifikanten Unterschied. Bei keiner der beiden Gruppen wurden ernsthafte akute oder spätere Komplikationen festgestellt.Schlussfolgerung:Unsere neue Standardfraktionierung für postoperative Strahlentherapien beträgt 30 Gy/3 Fraktionen.

Randomized Clinical Trial of Postoperative Strontium-90 Radiation Therapy for Pterygia

Background and Purpose:Postoperative adjuvant treatment with strontium-90 radiation therapy (RT) is a proven technique for reducing the recurrence of pterygium. This randomized trial was conducted to evaluate whether a total dose of 40 Gy provides a better local control rate than a total dose of 30 Gy for surgically resected pterygia.Patients and Methods:A single institutional randomized trial was conducted. Between 1999 and 2003, 74 pterygia in 71 patients were randomly allocated to 30 Gy/3 fractions/15 days (arm A) or to 40 Gy/4 fractions/22 days (arm B). Only primary pterygia for which RT could be started within 3 days of surgical resection were included. Postoperative RT was given by a strontium-90 eye applicator, and a dose of 10 Gy per fraction was delivered in weekly fractions (day 1, 8, 15, 22).Results:Of the 74 pterygia treated, 73 in 70 patients were analyzed. Of the 73 pterygia, 41 were allocated to arm A, and the remaining 32 to arm B. The 2-year local control rates for arm A and arm B were 85% and 75%, respectively, without significant difference. No serious acute and late complications were noted in either arm.Conclusion:Our new standard fractionation for postoperative RT for pterygia is 30 Gy/3 fractions.Ziel:Die postoperative adjuvante Behandlung mit Strontium-90-Strahlentherapie ist eine anerkannte Methode, um das Wiederauftreten von Pterygien zu vermeiden. Anhand der vorliegenden randomisierten Studie sollte untersucht werden, ob bei operativ entferntem Ptergium eine Dosis von 40 Gy eine bessere Kontrollrate als eine Dosis von 30 Gy bietet.Patienten und Methodik:Eine einzelinstitutionelle, randomisierte Untersuchung wurde durchgeführt. Zwischen 1999 und 2003 wurden 74 Pterygien bei 71 Patienten stichprobenartig entweder mit 30 Gy/3 Fraktionen/15 Tage (Gruppe A) oder 40 Gy/ 4 Fraktionen/22 Tage (Gruppe B) behandelt. Es wurden nur primäre Pterygien berücksichtigt, bei denen innerhalb von 3 Tagen nach der operativen Entfernung mit der RT begonnen werden konnte. Die postoperative RT wurde mit einem Strontium-90-Augenapplikator durchgeführt, und zwar in Dosen von 10 Gy pro wöchentlicher Teilbehandlung (Tag 1, 8, 15, 22).Ergebnisse:Von den 74 behandelten Pterygien wurden 73 von 70 Patienten analysiert. Von diesen 73 gehörten 41 zu Gruppe A, die übrigen 32 zu Gruppe B. Die 2-Jahres-Kontrollraten für Gruppe A und Gruppe B lagen bei 85% und 75% ohne signifikanten Unterschied. Bei keiner der beiden Gruppen wurden ernsthafte akute oder spätere Komplikationen festgestellt.Schlussfolgerung:Unsere neue Standardfraktionierung für postoperative Strahlentherapien beträgt 30 Gy/3 Fraktionen.

Randomized Clinical Trial of Postoperative Strontium-90 Radiation Therapy for Pterygia@@@Eine randomisierte klinische Studie zur postoperativen Strontium-90-Strahlentherapie für Pterygien: 30 Gy/ 3 Fraktionen versus 40 Gy/4 Fraktionen: Treatment Using 30 Gy/3 Fractions vs. 40 Gy/4 Fractions

Background and Purpose:Postoperative adjuvant treatment with strontium-90 radiation therapy (RT) is a proven technique for reducing the recurrence of pterygium. This randomized trial was conducted to evaluate whether a total dose of 40 Gy provides a better local control rate than a total dose of 30 Gy for surgically resected pterygia.Patients and Methods:A single institutional randomized trial was conducted. Between 1999 and 2003, 74 pterygia in 71 patients were randomly allocated to 30 Gy/3 fractions/15 days (arm A) or to 40 Gy/4 fractions/22 days (arm B). Only primary pterygia for which RT could be started within 3 days of surgical resection were included. Postoperative RT was given by a strontium-90 eye applicator, and a dose of 10 Gy per fraction was delivered in weekly fractions (day 1, 8, 15, 22).Results:Of the 74 pterygia treated, 73 in 70 patients were analyzed. Of the 73 pterygia, 41 were allocated to arm A, and the remaining 32 to arm B. The 2-year local control rates for arm A and arm B were 85% and 75%, respectively, without significant difference. No serious acute and late complications were noted in either arm.Conclusion:Our new standard fractionation for postoperative RT for pterygia is 30 Gy/3 fractions.Ziel:Die postoperative adjuvante Behandlung mit Strontium-90-Strahlentherapie ist eine anerkannte Methode, um das Wiederauftreten von Pterygien zu vermeiden. Anhand der vorliegenden randomisierten Studie sollte untersucht werden, ob bei operativ entferntem Ptergium eine Dosis von 40 Gy eine bessere Kontrollrate als eine Dosis von 30 Gy bietet.Patienten und Methodik:Eine einzelinstitutionelle, randomisierte Untersuchung wurde durchgeführt. Zwischen 1999 und 2003 wurden 74 Pterygien bei 71 Patienten stichprobenartig entweder mit 30 Gy/3 Fraktionen/15 Tage (Gruppe A) oder 40 Gy/ 4 Fraktionen/22 Tage (Gruppe B) behandelt. Es wurden nur primäre Pterygien berücksichtigt, bei denen innerhalb von 3 Tagen nach der operativen Entfernung mit der RT begonnen werden konnte. Die postoperative RT wurde mit einem Strontium-90-Augenapplikator durchgeführt, und zwar in Dosen von 10 Gy pro wöchentlicher Teilbehandlung (Tag 1, 8, 15, 22).Ergebnisse:Von den 74 behandelten Pterygien wurden 73 von 70 Patienten analysiert. Von diesen 73 gehörten 41 zu Gruppe A, die übrigen 32 zu Gruppe B. Die 2-Jahres-Kontrollraten für Gruppe A und Gruppe B lagen bei 85% und 75% ohne signifikanten Unterschied. Bei keiner der beiden Gruppen wurden ernsthafte akute oder spätere Komplikationen festgestellt.Schlussfolgerung:Unsere neue Standardfraktionierung für postoperative Strahlentherapien beträgt 30 Gy/3 Fraktionen.