Kayoko Ohnishi

Clinical outcomes of single-fraction stereotactic radiation therapy of lung tumors

The objective of the current study was to investigate the effects and the morbidities of single‐fraction stereotactic radiation therapy (SRT) for lung tumors.

Pretreatment Apparent Diffusion Coefficient of the Primary Lesion Correlates With Local Failure in Head-and-Neck Cancer Treated With Chemoradiotherapy or Radiotherapy

PURPOSE This study was performed to evaluate whether the apparent diffusion coefficient (ADC) of a primary lesion correlates with local failure in primary head-and-neck squamous cell carcinoma (HNSCC) treated with chemoradiotherapy or radiotherapy. METHODS AND MATERIALS We retrospectively studied 38 patients with primary HNSCC (12 oropharynx, 20 hypopharynx, 4 larynx, 2 oral cavity) treated with chemoradiotherapy or radiotherapy with radiation dose to gross tumor volume equal to or over 60 Gy and who underwent pretreatment magnetic resonance imaging, including diffusion-weighted imaging. Ten patients developed local failure during follow-up periods of 2.0 to 9.3 months, and the remaining 28 showed local control during follow-up periods of 10.5 to 31.7 months. The variables that could affect local failure (age, tumor volume, ADC, T stage, N stage, dose, treatment method, tumor location, and overall treatment time) were analyzed using logistic regression analyses for all 38 patients and for 17 patients with Stage T3 or T4 disease. RESULTS In univariate logistic analysis for all 38 cases, tumor volume, ADC, T stage, and treatment method showed significant (p < 0.05) associations with local failure. In multivariate analysis, ADC and T stage revealed significance (p < 0.01). In univariate logistic analysis for the 17 patients with Stage T3 or T4 disease, ADC and dose showed significant (p < 0.01) associations with local failure. In multivariate analysis, ADC alone showed significance (p < 0.05). CONCLUSIONS The results suggest that pretreatment ADC, along with T stage, is a potential indicator of local failure in HNSCC treated with chemoradiotherapy or radiotherapy.

Proton beam therapy for hepatocellular carcinoma with limited treatment options

The authors conducted a retrospective review to define the usefulness of proton beam therapy for patients who had hepatocellular carcinoma (HCC) with limited treatment options.

Proton Beam Therapy for Hepatocellular Carcinoma Patients with Severe Cirrhosis

Background and Purpose:Hepatocellular carcinoma (HCC) patients with severe cirrhosis are usually treated with supportive care because of their poor prognosis. However, the survival of severe cirrhotic patients has recently improved due to advanced treatments. The aim of this study was to define the role of proton beam therapy for HCC patients with severe cirrhosis.Patients and Methods:19 HCC patients with Child-Pugh class C cirrhosis received proton beam therapy. The hepatic tumors were solitary in 14 patients and multiple in five, and the tumor size was 25–80 mm (median 40 mm) in maximum diameter. No patient had regional lymph node or distant metastasis. Total doses of 50–84 Gy (median 72 Gy) in ten to 24 fractions (median 16) were delivered to the tumors.Results:Of the 19 patients, six, eight and four died of cancer, liver failure and intercurrent diseases, respectively, during the follow-up period of 3–63 months (median 17 months) after treatment. A remaining patient was alive with no evidence of disease 33 months after treatment. All but one of irradiated tumors were controlled during the follow-up period. Ten patients had new intrahepatic tumors outside the irradiated volume. The overall and progression-free survival rates were 53% and 47% at 1 year, respectively, and 42% each at 2 years. Performance status and Child-Pugh score were significant prognostic factors for survival. Therapy-related toxicity of grade 3 or more was not observed.Conclusion:Proton beam therapy for HCC patients with severe cirrhosis was tolerable. It may improve survival for patients with relatively good general condition and liver function.Hintergrund und Ziel:Patienten mit Leberzellkarzinom (HCC [„hepatocellular carcinoma“]) und schwerer Zirrhose werden aufgrund der schlechten Prognose gewöhnlich konservativ behandelt. Allerdings haben fortschrittliche Therapien in letzter Zeit zu einer Verbesserung der Überlebenszeit von Patienten mit schwerer Zirrhose geführt. Das Ziel der vorliegenden Studie war die Bestimmung der Rolle einer Protonentherapie für HCC-Patienten mit schwerer Zirrhose.Patienten und Methodik:19 HCC-Patienten mit Zirrhose der Child-Pugh-Klasse C wurden mit Protonenstrahlen behandelt. 14 Patienten wiesen einzelne und fünf Patienten multiple Lebertumoren auf. Hinsichtlich der Tumorgröße variierte der maximale Durchmesser dabei zwischen 25 und 80 mm (durchschnittlich 40 mm). Keiner der Patienten hatte regionäre Lymphknoten- oder Fernmetastasen in regionären oder entfernten Lymphknoten. Die Gesamtstrahlendosis betrug 50–84 Gy (durchschnittlich 72 Gy) und wurde in zehn bis 24 Fraktionen (durchschnittlich 16 Fraktionen) verabreicht.Ergebnisse:Im Nachuntersuchungszeitraum von 3–63 Monaten (durchschnittlich 17 Monate) verstarben sechs der insgesamt 19 Patienten an Krebs, acht an Leberversagen und vier an interkurrierenden Erkrankungen. Ein Patient war 33 Monate nach der Behandlung ohne Krankheitszeichen am Leben. Mit einer Ausnahme wurden alle Tumoren während der Nachuntersuchung mit entsprechenden Kontrollen verglichen. Zehn Patienten hatten intrahepatische Tumoren, die außerhalb des bestrahlten Bereichs lagen. Die Gesamt- und die progressionsfreie Überlebensrate betrugen nach 1 Jahr 53% und 47% und nach 2 Jahren 42%. Der Performance-Status und die Child-Pugh-Bewertung waren wichtige prognostische Faktoren für das Überleben.Schlussfolgerung:Die Protonentherapie war für Patienten mit Leberzellkarzinom und schwerer Zirrhose tolerabel. Die Behandlung könnte das Überleben von Patienten mit relativ gutem Allgemeinzustand und guter Leberfunktion verbessern.

Prediction of Local Failures with a Combination of Pretreatment Tumor Volume and Apparent Diffusion Coefficient in Patients Treated with Definitive Radiotherapy for Hypopharyngeal or Oropharyngeal Squamous Cell Carcinoma

Diffusion-weighted magnetic resonance imaging/Apparent diffusion coefficient/Hypopharyngeal squamous cell carcinoma/Oropharyngeal squamous cell carcinoma. Purpose: Th e purpose of this study was to investigate the clinical factors for predicting local failure after definitive radiotherapy in oropharyngeal or hypopharyngeal squamous cell carcinoma. Materials and Methods: Between July 2006 and December 2008, 64 consecutive patients with squamous cell carcinoma of the hypopharynx or the oropharynx treated with definitive radiotherapy were included in this study. Clinical factors, such as pretreatment hemoglobin (Hb) level, T-stage, gross tumor volume of primary tumors (pGTV), and maximum standardized uptake value (SUVmax) on FDG-PET, were evaluated for the correlation with local failure. A subset analysis of 32 patients with MR images including diffusionweighted images (DWI) as a pretreatment evaluation was also performed. The Kaplan-Meier curves, the log-rank test, and the Cox proportional hazards model were used to evaluate these clinical factors. Results: Eleven of 64 patients experienced local recurrence, with a median follow-up time of 15 months. In the univariate analysis, Hb level (p = 0.0261), T-stage (p = 0.012), pGTV (p = 0.0025), and SUVmax (p = 0.024) were significantly associated with local failure. In the multivariate analysis, pGTV (p = 0.0070) remained an adverse factor for local control. In the subset analysis of 32 patients with DWI, the median apparent diffusion coefficient (ADC) value of primary tumors on DWI was 0.79 × 10 –3 mm 2 /s (range, 0.40–1.60 × 10 –3 mm 2 /s). Patients with a high ADC value (> 0.79 × 10 –3 mm 2 /s) had a significantly lower local control rate than patients with a low ADC value (100% vs. 44%, p = 0.0019). The rate of local failure among patients with a large pGTV and a high ADC value was 55% (6/11), whereas no local failures occurred (0%, 0/21) among patients with a small pGTV or a low ADC. Co nclusions: These results suggest that a combination of a large tumor volume and a high ADC value could be predictive of local recurrence after definitive radiotherapy in hypopharyngeal or oropharyngeal squamous cell carcinoma.

Proton irradiation in a single fraction for hepatocellular carcinoma patients with uncontrollable ascites. Technical considerations and results.

Purpose:To present technical considerations and results of proton irradiation in a single fraction for hepatocellular carcinoma (HCC) patients with uncontrollable ascites.Patients and Methods:Three HCC patients with uncontrollable ascites underwent proton irradiation of 24 Gy in a single fraction. Hepatic tumors were solitary in two patients, and multiple in one, and tumor sizes were 30, 30, and 33 mm in maximum diameter. No patient had lymph node or distant metastases. The center position of radiation fields was determined and the beam range was adjusted, using CT data taken immediately before irradiation to compensate for changes in the volume of ascites. Adjustment of the beam range was within 6 mm in water-equivalent thickness.Results:All irradiated tumors showed objective responses, and were controlled during the follow-up period. Of the three patients, two were alive with no evidence of disease at 13 and 30 months, respectively, after treatment. The remaining patient died of ruptured esophageal varices 6 months after treatment. No therapy-related toxicity of grade 3 or more was observed.Conclusion:Proton beams were successfully adjusted immediately before irradiation. Single-dose irradiation with precisely adjusted proton beams may be tolerable for HCC patients with uncontrollable ascites.Ziel:Vorstellung technischer Überlegungen und der Ergebnisse von Protonenbestrahlungen in einer einzigen Fraktion bei Patienten mit Leberzellkarzinom (HCC [„hepatocellular carcinoma“]) und unkontrollierbarem Aszites.Patienten und Methodik:Drei HCC-Patienten mit unkontrollierbarem Aszites erhielten eine Protonenbestrahlung von 24 Gy als Einzelfraktion. Bei den Lebertumoren handelte es sich in zwei Fällen um solitäre Tumoren und in einem Fall um multiple Tumoren, deren maximaler Durchmesser jeweils 30, 30 und 33 mm betrug. Bei keinem der Patienten lagen Lymphknoten- oder Fernmetastasen vor. Das Zentrum des Bestrahlungsbereichs wurde anhand der unmittelbar vor der Bestrahlung erhobenen CT-Daten festgelegt, und der Strahlbereich wurde entsprechend eingestellt, um Änderungen im Aszitesvolumen auszugleichen. Die Einstellung des Strahlbereichs lag innerhalb einer wasseräquivalenten Schichtdicke von 6 mm.Ergebnisse:Bei allen bestrahlen Tumoren wurde eine objektive Veränderung registriert und während der Beobachtungszeit kontrolliert. Zwei der drei Patienten waren jeweils 13 und 30 Monate nach der Behandlung ohne Anzeichen der Krankheit am Leben. Der andere Patient verstarb 6 Monate nach der Behandlung an einer Ruptur ösophagealer Varizen. Therapiebezogene Toxizität eines Schweregrades von 3 oder höher wurde nicht beobachtet.Schlussfolgerung:Protonenstrahlen wurden unmittelbar vor der Bestrahlung erfolgreich eingestellt. Die Bestrahlung als Einzeldosis mit einem genau eingestellten Protonenstrahl scheint für HCC-Patienten mit unkontrollierbarem Aszites tolerierbar zu sein.

Proton Irradiation in a Single Fraction for Hepatocellular Carcinoma Patients with Uncontrollable Ascites

Purpose:To present technical considerations and results of proton irradiation in a single fraction for hepatocellular carcinoma (HCC) patients with uncontrollable ascites.Patients and Methods:Three HCC patients with uncontrollable ascites underwent proton irradiation of 24 Gy in a single fraction. Hepatic tumors were solitary in two patients, and multiple in one, and tumor sizes were 30, 30, and 33 mm in maximum diameter. No patient had lymph node or distant metastases. The center position of radiation fields was determined and the beam range was adjusted, using CT data taken immediately before irradiation to compensate for changes in the volume of ascites. Adjustment of the beam range was within 6 mm in water-equivalent thickness.Results:All irradiated tumors showed objective responses, and were controlled during the follow-up period. Of the three patients, two were alive with no evidence of disease at 13 and 30 months, respectively, after treatment. The remaining patient died of ruptured esophageal varices 6 months after treatment. No therapy-related toxicity of grade 3 or more was observed.Conclusion:Proton beams were successfully adjusted immediately before irradiation. Single-dose irradiation with precisely adjusted proton beams may be tolerable for HCC patients with uncontrollable ascites.Ziel:Vorstellung technischer Überlegungen und der Ergebnisse von Protonenbestrahlungen in einer einzigen Fraktion bei Patienten mit Leberzellkarzinom (HCC [„hepatocellular carcinoma“]) und unkontrollierbarem Aszites.Patienten und Methodik:Drei HCC-Patienten mit unkontrollierbarem Aszites erhielten eine Protonenbestrahlung von 24 Gy als Einzelfraktion. Bei den Lebertumoren handelte es sich in zwei Fällen um solitäre Tumoren und in einem Fall um multiple Tumoren, deren maximaler Durchmesser jeweils 30, 30 und 33 mm betrug. Bei keinem der Patienten lagen Lymphknoten- oder Fernmetastasen vor. Das Zentrum des Bestrahlungsbereichs wurde anhand der unmittelbar vor der Bestrahlung erhobenen CT-Daten festgelegt, und der Strahlbereich wurde entsprechend eingestellt, um Änderungen im Aszitesvolumen auszugleichen. Die Einstellung des Strahlbereichs lag innerhalb einer wasseräquivalenten Schichtdicke von 6 mm.Ergebnisse:Bei allen bestrahlen Tumoren wurde eine objektive Veränderung registriert und während der Beobachtungszeit kontrolliert. Zwei der drei Patienten waren jeweils 13 und 30 Monate nach der Behandlung ohne Anzeichen der Krankheit am Leben. Der andere Patient verstarb 6 Monate nach der Behandlung an einer Ruptur ösophagealer Varizen. Therapiebezogene Toxizität eines Schweregrades von 3 oder höher wurde nicht beobachtet.Schlussfolgerung:Protonenstrahlen wurden unmittelbar vor der Bestrahlung erfolgreich eingestellt. Die Bestrahlung als Einzeldosis mit einem genau eingestellten Protonenstrahl scheint für HCC-Patienten mit unkontrollierbarem Aszites tolerierbar zu sein.

Postoperative radiotherapy in patients with salivary duct carcinoma: clinical outcomes and prognostic factors

This study sought to investigate the clinical outcome and the role of postoperative radiotherapy for patients with salivary duct carcinoma (SDC) who had undergone surgery and postoperative radiotherapy. We performed a retrospective analysis of 25 SDC patients treated between 1998 and 2011 with surgery and postoperative radiotherapy. The median prescribed dose was 60 Gy (range, 49.5–61.4 Gy). The clinical target volume (CTV) was defined as the tumor bed in four patients, the tumor bed and ipsilateral neck in 14 patients, and the tumor bed and bilateral neck in six patients. Local control (LC), disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and prognostic variables were analyzed with the log-rank test. The 5-year LC, DFS and OS were 67%, 45% and 47%, respectively. Disease recurrence was found in 12 patients: seven as local, four as regional and eight as distant failure. Perineural and lymphovascular invasion was a significant prognostic factor for LC (P = 0.03). Local failure was common, and the presence of local recurrence significantly affected the OS (P < 0.05). We conclude that surgery and postoperative radiotherapy is expected to decrease the risk of local failure and contribute to good prognoses for patients with SDC. It might be advisable to have the CTV include the cranial nerves involved and the corresponding parts of the skull base in cases of pathologically positive perineural invasion.

A clinical evaluation of visual feedback-guided breath-hold reproducibility of tumor location

The purpose of this study was to evaluate the reproducibility of visual feedback-guided breath-hold using a machine vision system with a charge-coupled device camera and a monocular head-mounted display. Sixteen patients with lung tumors who were treated with stereotactic radiotherapy were enrolled. A machine vision system with a charge-coupled device camera was used for monitoring respiration. A monocular head-mounted display was used to provide the patient with visual feedback about the breathing trace. The patients could control their breathing so that the breathing waveform would fall between the upper and lower threshold lines. Planning and treatment were performed under visual feedback-guided expiratory breath-hold. Electronic portal images were obtained during treatment. The range of cranial-caudal motion of the tumor location during each single breath-hold was calculated as the intra-breath-hold (intra-BH) variability. The maximum displacement between the two to five averaged tumor locations of each single breath-hold was calculated as the inter-breath-hold (inter-BH) variability. All 16 patients tolerated the visual feedback-guided breath-hold maneuvers well. The intra- and inter-BH variability of all patients was 1.5 +/- 0.6 mm and 1.2 +/- 0.5 mm, respectively. A visual feedback-guided breath-hold technique using the machine vision system is feasible with good breath-hold reproducibility.

Clinical results of definitive chemoradiotherapy for patients with synchronous head and neck squamous cell carcinoma and esophageal cancer.

Objectives:To assess the efficacy and toxicity of radical chemoradiotherapy for patients with synchronous head and neck squamous cell carcinoma (HNSCC) and esophageal cancer (EC). Methods:Thirty-four patients with synchronous HNSCC and EC were treated mainly with radical chemoradiotherapy at the same time. Median external radiation dose for HNSCC and EC was 70 Gy (range, 60–70.5 Gy), except for 2 patients with tongue cancer, who underwent brachytherapy and 60 Gy (range, 45–70 Gy), respectively. Thirty-one patients were treated with concurrent chemoradiotherapy with cisplatin and/or 5-fluorouracil or TS-1 (oral anticancer agent that combines tegafur, a metabolically activated prodrug of 5-fluorouracil, with 5-chloro-2, 4-dihydoroxypyridine, and potassium oxonate). Results:Thirty-three patients completed the intended treatment. The response rate was 94%, with 26 complete responses (76%) and 6 partial responses (18%). At a median follow-up of 17.3 months, 2-year rates of overall survival, cause-specific survival, and disease-free survival were 44%, 52%, and 33%, respectively. Initial failure patterns were local failure in 14 patients (63%), regional progression in 3 patients (13%), and distant metastasis in 6 patients (27%). The most common acute toxicity was myelosuppression, with 8 patients experiencing grade 3–4 toxicity. Three patients experienced grade 3 mucositis and pharyngitis. No patients experienced late morbidity of grade 3 or higher. Conclusions:Definitive chemoradiotherapy for patients with synchronous HNSCC and EC is feasible with a low mortality rate and acceptable morbidity.