Naoto Shikama

Lack of benefit of spinal irradiation in the primary treatment of intracranial germinoma : A multiinstitutional retrospective review of 180 patients

The current study assessed the contribution of spinal irradiation to the treatment outcome of patients with intracranial germinoma.

Experiences of 23 Patients ≥ 90 Years of Age Treated With Radiation Therapy

PURPOSE To present 23 patients > or = 90 years old treated with radiotherapy, and to retrospectively evaluate the results of radiotherapy and tolerance in these patients. METHODS AND MATERIALS The clinical records of 27 patients over 90 years of age who were treated with radiotherapy at the Department of Radiology, Shinshu University Hospital, and eight affiliated general hospitals from 1990 until 1995 were reviewed. The strategy of radiotherapy was individually planned depending on the stage of the disease and performance status (PS) of the patient; however, it was not modified, based solely on chronologic age. The overall survival rate and disease-free survival rate were determined using the Kaplan-Meier method. The Radiation Therapy Oncology Group scoring criteria of acute and late reactions of radiation therapy were used. RESULTS This group of patients accounted for 0.37% of all patients treated with radiotherapy in these hospitals. Of these, 23 patients in whom cancer was pathologically confirmed and whose follow-up data were available for retrospective analysis were included in the final evaluation of data. The age of the 23 patients ranged from 90 to 96 years (median 93). Tumor was untreated and in the early stage in five patients, locoregionally advanced in 13, recurrent in four, and systemic in one. Definitive radiation therapy was administered in 12 patients (13 sites), preoperative intent in one, and palliative intent in 10. The period of observation ranged from 2.5 to 6 years (median 18 months). Seven patients were alive for 15-67 months. Fourteen patients died because of intercurrent diseases or senility associated with active cancer, and two because of senility without evidence of cancer. The overall and relapse-free survival rates were 65% and 30% at 1 year and 30% and 21% at 2 years, respectively. Definitive radiation therapy was completed in 13 of 13 patients (100%), and local control was attained in 9 of 13 patients at 6 months (62%). Palliative radiation therapy was completed as intended in 7 of 11 (64%), and effects of palliation were observed in 9 of 11 patients (81%). Acute dermatitis, mucositis, pharyngitis, esophagitis, and cystitis of grade 2-3 related to the definitive radiation therapy were tolerable for the patients with good PS. It took 3-7 weeks (median 5) for acute moist desquamation of six lesions of skin cancer to heal. Depending on the radiation doses, grade 1-2 atrophy of skin and telangiectasia were documented for eight patients followed up for more than 1 year. A brief description of representative case is presented. CONCLUSION Patients older than 90 years with good PS may tolerate the acute effects of radiotherapy administered according to conventional fractionation schedules. Definitive radiation therapy should be considered, when applicable, even for patients older than 90 years.

Localized aggressive non-Hodgkin’s lymphoma of the nasal cavity: a survey by the Japan Lymphoma Radiation Therapy Group

PURPOSE To clarify the role of radiotherapy and chemotherapy in the treatment of patients with localized aggressive non-Hodgkins lymphomas (NHL) originating in the nasal cavity. METHODS AND MATERIALS The survey, administered at 25 Japanese institutes in 1998, enabled us to collect the clinical data for 787 patients with localized aggressive NHL who were treated between 1988 and 1992. RESULTS There were 42 patients (5%) with nasal lymphomas. Twelve of these patients received radiotherapy alone, and 30 were treated with a combination of radiotherapy and chemotherapy. The median radiation dose was 47 Gy (22-66). Twelve patients were reviewed histopathologically according to REAL (Revised European-American Classification of Lymphoid neoplasms) classification. T-cell or natural killer (NK) cell lymphomas were detected in 9 patients (75%), and diffuse large B-cell lymphomas in 3 (25%). The 5-year overall and disease-free survival (DFS) rates of all patients were 57% and 59%, respectively. The 5-year DFS rate for the 30 patients treated with the combined therapy was 64% and that for the 12 patients treated with radiotherapy alone was 46% (p = 0.021). For the 34 patients with stage-modified International Prognostic Index (m-IPI) 0-1, the 5-year DFS rates of those treated with the combined therapy and radiotherapy alone were 68% and 45%, respectively (p = 0.020), but there was no difference in DFS rate among the two groups of patients with m-IPI 2-3. The 5-year local control rates of the patients who received >46 Gy (n = 22) and < or =46 Gy (n = 20) were 95% and 76% (p = 0.087), respectively. There was no significant difference among the 5-year DFS rates (62% vs. 67%) and local control rates (87% vs. 100%) of the patients with T-cell or NK-cell lymphoma and diffuse large B-cell lymphoma. CONCLUSIONS Patients with nasal lymphomas (m-IPI 0-1) should be treated with combined therapy. For the patients with high risk (m-IPI 2-3), the effectiveness of combined therapy was not clarified because of the small number of the patients. A high radiation dose >46 Gy may need to be used to achieve good local control.

Mucosa-Adhesive Water-Soluble Polymer Film for Treatment of Acute Radiation-Induced Oral Mucositis

PURPOSE To examine the usefulness and safety of a mucosa-adhesive water-soluble polymer film (AD film) containing anesthetics and antibiotics for the treatment of acute radiation-induced oral mucositis. MATERIALS AND METHODS To prepare AD films, 600 mg of hydroxy-propyl-cellulose was dissolved in ethyl alcohol, and mixed with a solution containing tetracaine, ofloxacine, miconazole, guaiazulene, and triacetin. The gel obtained was dried to form 30 translucent round sheets (20 mg per sheet) of 7.5 cm in diameter and 0.2 mm in thickness. The AD film showed excellent adhesive and coating properties when placed on wet oral mucosa. From 1993 to 1994, we used the AD film in 25 patients with acute radiation-induced oral mucositis, in an attempt to alleviate their pain and prevent secondary oral infection. All patients had received definitive radiotherapy for oral carcinoma. Intensity and duration of oral pain from mucositis, relief rates at rest and while eating, and presence of bacterial and/or fungal infection were compared with those of 27 patients treated with topical anesthetics (viscous lidocaine, Xylocaine and/or general systemic analgesics from 1990 to 1992 (NonAD Group). RESULTS The intensity of oral pain was the same in the two groups. The mean duration of pain of the AD film Group (10 days) was significantly shortened compared with the NonAD Group (15 days). The rates of complete pain relief at rest and while eating of the AD film Group were statistically higher than those of the NonAD Group: 82% vs. 44%, and 68% vs. 22%, respectively. No secondary bacterial or fungal infections were observed in the AD film Group, whereas 4 cases of documented infections were found in the NonAD Group. No acute or chronic adverse effects of AD film were observed during the 3-year follow-up period. The rates for local control of oral carcinoma and overall survival, at the end of the follow-up period, were 96% and 87% for the AD film Group vs. 92% and 85% for the NonAD Group, respectively. CONCLUSION The AD film, containing topical anesthetics and antibiotics, proved useful to alleviate pain due to acute radiation-induced oral mucositis, maintain good peroral feeding, and prevent secondary oral infections, without inducing adverse reactions.

Prospective multi-institutional study of definitive radiotherapy with high-dose-rate intracavitary brachytherapy in patients with nonbulky (<4-cm) stage i and II uterine cervical cancer (JAROG0401/JROSG04-2)

PURPOSE To determine the efficacy of a definitive radiotherapy protocol using high-dose-rate intracavitary brachytherapy (HDR-ICBT) with a low cumulative dose schedule in nonbulky early-stage cervical cancer patients, we conducted a prospective multi-institutional study. METHODS AND MATERIALS Eligible patients had squamous cell carcinoma of the intact uterine cervix, Federation of Gynecologic Oncology and Obstetrics (FIGO) stages Ib1, IIa, and IIb, tumor size <40 mm in diameter (assessed by T2-weighted magnetic resonance imaging), and no pelvic/para-aortic lymphadenopathy. The treatment protocol consisted of whole-pelvis external beam radiotherapy (EBRT) of 20 Gy/10 fractions, pelvic EBRT with midline block of 30 Gy/15 fractions, and HDR-ICBT of 24 Gy/4 fractions (at point A). The cumulative biologically effective dose (BED) was 62 Gy(10) (α/β = 10) at point A. The primary endpoint was the 2-year pelvic disease progression-free (PDPF) rate. All patients received a radiotherapy quality assurance review. RESULTS Between September 2004 and July 2007, 60 eligible patients were enrolled. Thirty-six patients were assessed with FIGO stage Ib1; 12 patients with stage IIa; and 12 patients with stage IIb. Median tumor diameter was 28 mm (range, 6-39 mm). Median overall treatment time was 43 days. Median follow-up was 49 months (range, 7-72 months). Seven patients developed recurrences: 3 patients had pelvic recurrences (2 central, 1 nodal), and 4 patients had distant metastases. The 2-year PDPF was 96% (95% confidence interval [CI], 92%-100%). The 2-year disease-free and overall survival rates were 90% (95% CI, 82%-98%) and 95% (95% CI, 89%-100%), respectively. The 2-year late complication rates (according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer of Grade ≥ 1) were 18% (95% CI, 8%-28%) for large intestine/rectum, 4% (95% CI, 0%-8%) for small intestine, and 0% for bladder. No Grade ≥ 3 cases were observed for genitourinary/gastrointestinal late complications. CONCLUSIONS These results suggest that definitive radiotherapy using HDR-ICBT with a low cumulative dose schedule (BED, 62 Gy(10) at point A) can provide excellent local control without severe toxicity in nonbulky (<4-cm) early-stage cervical cancer.

Treatment of primary intraocular lymphoma with radiation therapy : A multi-institutional survey in Japan

This study evaluated the clinical features and treatment outcome of 15 patients with primary intraocular lymphoma. There were nine females, with a median age of 68 years. Thirteen patients presented with bilateral lesions and median time from the onset of symptoms to diagnosis was 12 months. All but one showed the B-cell phenotype. All patients received radiation therapy (RT) with a median of 41 Gy and 10 were administered chemotherapy as well. Three patients were treated with high-dose methotrexate and nine received prophylactic cranial irradiation (PCI) with a median of 30.6 Gy. Thirteen patients obtained a complete remission. The 2-year overall and disease free survival were 74% and 58%, respectively. Although only one patient experienced local recurrence, PCI did not prevent intracranial recurrence. One patient developed a grade 3 cognitive disturbance. It was concluded that ocular RT was effective to control primary lesions. However, some modifications are indispensable to improve outcomes.

Relationship of 31P MR Spectroscopy to the Histopathological Grading of Chronic Hepatitis and Response to Therapy

Purpose: In vivo phosphorus (31P MR spectroscopy (31P MRS) was performed in the human liver in order to investigate the relation between: the ratios of phosphorus metabolites in the liver; the histopathological grading of chronic hepatitis; and the response to therapy Material and Methods: Hepatic 31P MRS using the DRESS method (depthresolved surface-coil spectroscopy) was carried out in 45 patients with chronic viral hepatitis or autoimmune hepatitis, and in 16 control subjects. We measured the ratios of the peak areas of phosphomonoesters (PME), inorganic phosphate (Pi), or phosphodiesters (PDE) to the peak area of β-adenosine triphosphate (ATP) Results: The PDE/ATP ratio of patients with chronic hepatitis or liver cirrhosis was lower than that of control subjects (liver cirrhosis=0.74; chronic active hepatitis=1.13–1.21; normal=1.43); only a small difference was found in the PME/ATP and Pi/ATP ratios. There was no correlation between the spectra and histopathological grading or response to therapy, but the response to therapy was poor when a reduced PDE/ATP ratio was present Conclusion: The PDE/ATP ratio measured by 31P MRS makes it possible to identify the transition of chronic active hepatitis into liver cirrhosis with a poor response to therapy

Alternating chemoradiotherapy for nasopharyngeal cancer using cisplatin and 5-fluorouracil: a preliminary report of phase II study

5613 Background: Nasopharyngeal cancer (NPC) is characterized by a high frequency of distant metastasis and mucositis was a marked problem even when radiotherapy (RT) alone was performed. Considering these characteristics of NPC, alternating chemoradiotherapy (ALT-CRT) may be a useful method of treating NPC because sufficient amount of anti-tumor agents can be administered together with a low frequency of mucositis compared to concurrent chemoradiotherapy (CRT). METHODS The subjects consisted of 16 patients with stage II, 25 patients with stage III and 26 patients with stage IV . Using 6 MV photon, RT was performed at an exposure of 1.8Gy 5 times a week. That is, a total absorbed dose of 36 Gy was irradiated between the basal of skull and supraclavicular fossa. After decreasing the irradiation field, an absorbed dose of 30-34Gy was additionally given thereafter. One course of chemotherapy (CT) consisted of the administration of 5-FUdepends on document reviewat a dose of 800 mg/m2/24 h for 5 days (days 1-5) and CDDP at a dose of 50 mg/m2/24 h for 2 days (days 6-7), and a total of 3 courses of CT was performed. During the ALT-CRT, CT was performed initially; and 2-3 days after completing the CT, RT was performed for 4 weeks. Thereafter, CT and RT were performed alternately. RESULTS The scheduled courses of ALT-CRT were completed in 57 (87%) of 67 patients. No severe adverse effects were noted in any other patients. In these 67 patients, the overall 3-year survival rate was 93%, and the progression free survival rate was 80% (The median follow up times was 33 months). CONCLUSIONS This method of ALT-CRT yielded higher or at least similar survival rate and lower toxicities than concurrent CRT, and we believed that this method can be used in a controlled clinical trial in the future to compare therapeutic results with those of the Intergroup 0099 Trial No significant financial relationships to disclose.

Measuring Quality of Life in Patients with Breast Cancer: A Systematic Review of Reliable and Valid Instruments Available in Japan

BackgroundLittle is known about the availability and psychometric properties of instruments to measure quality of life (QOL) in clinical research on Japanese patients with breast cancer. The purpose of this systematic review is to find reliable and valid instruments available in Japan, and to summarize their characteristics.MethodsInstruments available in Japan were found through a systematic search of the literature. Each instrument identified was evaluated for item development, reliability, validity, interpretability and utility.ResultsSix questionnaires to measure health-related QOL (the QOL-ACD, the EORTC QLQ-C30, the EORTC QLQ-BR23, the FACT-B, the SF-36, the WHO/QOL-26) and five scales to quantify the psychological burden (the STAI, the POMS, the SDS, the HADS, the GHQ), for which reliability and validity have been documented, are available in Japanese. All instruments were developed in foreign countries except for the QOL-ACD. Two of the QOL questionnaires were specific to breast cancer (the EORTC QLQ-BR23, the FACT-B). Though the measurements can be interpreted in some manner, the meaning of change scores over time has been documented for only three instruments (the EORTC QLQ-C30, the FACT-B, and the GHQ).ConclusionsThe review provides grounds for designing and implementing quantitative research on QOL of breast cancer patients in Japan. Methodological challenges, however, continue, particularly for validating instruments with regard to various study populations of Japanese people and demonstrating the clinical importance of change scores.

Variability in Bladder Volumes of Full Bladders in Definitive Radiotherapy for Cases of Localized Prostate Cancer

AbstractBackground and Purpose:To evaluate variation in bladder volume of full bladders in definitive radiotherapy for localized prostate cancer and to investigate potential predictors of increased bladder volume variations.Patients and Methods:In 40 patients, the bladder volume was measured with megavoltage computed tomography (MVCT) imaging performed just before irradiation during the administration of the 1st fraction (#1), the 10th fraction (#10), the 20th fraction (#20), and the 30th fraction (#30). Patients were instructed to avoid urinating for 60–90 minutes before the planning CT (pln-CT) scan and before daily irradiation. Patients were also encouraged to drink an unspecified volume of liquid that would result in a clear but tolerable urge to urinate.Results:The population-mean bladder volume (±1SD) was 219 ml (±83 ml) at the planning CT scan (pln-CT), 186 ml (±96 ml) at #1, 149 ml (±73 ml) at #10, 137 ml (±59 ml) at #20, and 136 ml (±60 ml) at #30. The mean intrapatient variation in bladder volume (1 SD relative to the mean bladder volume of each patient) was 38% (range: 10–84%). The bladder volume at the pln-CT was correlated with the intrapatient variance in bladder volume with a correlation coefficient of 0.54 and p <0.001.Conclusion:We observed a significant decline in bladder volumes during the course of radiotherapy. The bladder volume at the pln-CT was a significant predictor of increased bladder volume variations.ZusammenfassungHintergrund und Zweck:Die Evaluierung der Schwankungen des Blasenvolumens gefüllter Blasen in der definitiven Radiotherapie bei lokalisiertem Prostatakrebs sowie die Untersuchung potenzieller Prädiktoren für erhöhte Schwankungen des Blasenvolumens.Patienten und Methoden:Das Blasenvolumen von vierzig Patienten wurde mittels Megavoltage-Computertomographie (MVCT) bestimmt, die bei der Verabreichung der 1. Fraktion (#1), der 10. Fraktion (#10), der 20. Fraktion (#20) und der 30. Fraktion (#30) kurz vor der Bestrahlung durchgeführt wurde. Die Patienten wurden angewiesen, 60–90 Minuten vor dem Planungs-CT (pln-CT)- Scan und vor der täglichen Bestrahlung nicht zu urinieren. Die Patienten wurden zudem ermuntert, eine nicht näher bestimmte Menge an Flüssigkeit zu sich zu nehmen, um einen deutlichen aber tolerierbaren Harndrang herbeizuführen.Ergebnisse:Der Mittelwert der Grundgesamtheit des Blasenvolumens (±1SA) lag beim Planungs-CT-Scan (pln-CT) bei 219 ml (±83 ml), 186 ml (±96 ml) bei #1, 149 ml (±73 ml) bei #10, 137 ml (±59 ml) bei #20 und 136 ml (±60 ml) bei #30. Der Mittelwert der Schwankung des Blasenvolumens innerhalb eines Patienten (1SA bezogen auf den Mittelwert des Blasenvolumens des einzelnen Patienten) lag bei 38 % (Spannweite: 10–84 %). Das Blasenvolumen zum Zeitpunkt des pln-CT wurde mit der Streuung des Blasenvolumens innerhalb eines Patienten korreliert, woraus sich ein Korrelationskoeffizient von 0,54 mit p <0,001 ergab.Fazit:Im Laufe der Radiotherapie konnte eine deutliche Verringerung der Blasenvolumen festgestellt werden. Das Blasenvolumen zum Zeitpunkt des pln-CT-Scans erwies sich als signifikanter Prädiktor erhöhter Schwankungen im Blasenvolumen.