Kensei Nakata

Multi-institutional Analysis of Solitary Extramedullary Plasmacytoma of the Head and Neck Treated with Curative Radiotherapy

PURPOSE The purpose of this study was to elucidate the efficacy and optimal method of radiotherapy in the management of solitary extramedullary plasmacytoma occurring in the head and neck regions (EMPHN). METHODS AND MATERIALS Sixty-seven patients (43 male and 24 female) diagnosed with EMPHN between 1983 and 2008 at 23 Japanese institutions were reviewed. The median patient age was 64 years (range, 12-83). The median dose administered was 50 Gy (range, 30-64 Gy). Survival data were calculated by the Kaplan-Meier method. RESULTS The median follow-up duration was 63 months. Major tumor sites were nasal or paranasal cavities in 36 (54%) patients, oropharynx or nasopharynx in 16 (23%) patients, orbita in 6 (9%) patients, and larynx in 3 (5%) patients. The 5- and 10-year local control rates were 95% and 87%, whereas the 5- and 10-year disease-free survival rates were 56% and 54%, respectively. There were 5 (7.5%), 12 (18%), and 8 (12%) patients who experienced local failure, distant metastasis, and progression to multiple myeloma, respectively. In total, 18 patients died, including 10 (15%) patients who died due to complications from EMPHN. The 5- and 10-year overall survival (OS) rates were 73% and 56%, respectively. Radiotherapy combined with surgery was identified as the lone significant prognostic factor for OS (p = 0.04), whereas age, gender, radiation dose, tumor size, and chemotherapy were not predictive. No patient experienced any severe acute morbidity. CONCLUSIONS Radiotherapy was quite effective and safe for patients with EMPHN. Radiotherapy combined with surgery produced a better outcome according to survival rates. These findings require confirmation by further studies with larger numbers of patients with EMPHN.

HIGH-DOSE-RATE INTRACAVITARY BRACHYTHERAPY: RESULTS OF ANALYSES OF LATE RECTAL COMPLICATIONS

PURPOSE To examine the incidence of radiation-induced late rectal complications by analyzing the data of measured rectal doses in patients with cancer of the uterine cervix treated with high-dose-rate intracavitary brachytherapy. METHODS AND MATERIALS We measured doses to the rectum in 105 patients with cancer of the cervix during high-dose-rate intracavitary brachytherapy with a semiconductor dosimeter that can measure five points in the rectum simultaneously. On the basis of these measurements, equivalent doses, to which the biologically equivalent doses were converted as if given as fractionated irradiation at 2 Gy/fraction, were calculated as components of the cumulative dose at five rectal points in intracavitary brachytherapy combined with the external whole pelvic dose. RESULTS The calculated values of equivalent doses for late effects at the rectum ranged from 15 to 100 Gy (median 60 Gy for patients who did not develop complications and 76 Gy for patients who subsequently developed Grade II or III complications). When converted to a graph of absolute rectal complication probability, the data could be fitted to a sigmoid curve. The data showed a very definite dose-response relationship, with a threshold for complications at approximately 50 Gy and the curve starting to rise more steeply at approximately 60 Gy. The steepest part of the curve had a slope equivalent to approximately 4% incidence/1 Gy increase in equivalent doses. CONCLUSION The radiation tolerance dose, 5% and 50% complication probability, was about 64 and 79 Gy, respectively. Our data almost agree with the prescribed dose for the rectum for the radiation tolerance doses on the basis of the recorded human and animal data. The probability of rectal complications increased drastically after the maximal rectal dose was >60 Gy.

A clinical study of hypoxia using endogenous hypoxic markers and polarographic oxygen electrodes.

Purpose:To examine various kinds of endogenous hypoxia markers’ expression in the tissues of uterine cervix cancer and to elucidate the characteristics and pitfalls when they are used as a hypoxia marker, by comparing these expressions with tumor oxygen partial pressure (pO2) values.Patients and Methods:Assessment of pO2 using polarographic oxygen electrodes was performed in 69 patients with cervix carcinomas. Biopsies were taken from the region of electrode measurements. Expression of endogenous hypoxic markers in biopsy specimens such as vascular endothelial growth factor, glucose transporter-1 (GLUT-1), involucrin, and osteopontin was detected by immunohistochemistry. A double immunolabeling technique with GLUT-1 and MIB-1 as a marker of proliferation was also performed.Results:There was no significant correlation between expression of endogenous hypoxic markers and pO2. The only significant association seen was between the fraction of necrosis and pO2. A significant but weak correlation was found among expression of endogenous hypoxic markers. The levels of necrosis were related negatively with levels of expression of endogenous hypoxic markers. The double immunolabeling technique with GLUT-1 and MIB-1 indicated that there were about 20% MIB-1-positive tumor cells without GLUT-1 expression in tissues adjacent to areas of necrosis.Conclusion:The existence of necrosis affected the expression of endogenous hypoxic markers. Some hypoxic tumor cells without expressions of hypoxia markers can maintain clonogenicity and influence the treatment results. The combined use of hypoxic markers is recommended because their expression is influenced by factors other than hypoxia.Ziel:Prüfung der Expression verschiedener endogener Hypoxiemarker in Zervixkarzinom-Geweben und Ermitteln ihrer Eignung als Marker zur Hypoxiemessung durch Vergleich mit den Werten des Sauerstoffpartialdrucks (pO2) im Tumor.Patienten und Methodik:Polarographische pO2-Bestimmungen wurden bei 69 Zervixkarzinom-Patientinnen durchgeführt. Es wurden aus dem Bereich der Messelektrode Biopsien genommen. In den Gewebeproben wurde immunhistologisch die Expression endogener Hypoxiemarker—wie Vascular Endothelial Growth Factor (VEGF), Glukose-Transporter-1 (GLUT-1), Involucrin und Osteopontin—nachgewiesen. Eine immunhistologische Doppelmarkierung mit GLUT-1 and MIB-1 als Proliferationsmarker wurde ebenfalls durchgeführt.Ergebnisse:Es bestand keine signifikante Korrelation zwischen der Expression endogener Hypoxiemarker und pO2. Die einzige signifikante Assoziation fand sich zwischen Nekrose-Anteil und pO2. Es zeigte sich eine signifikante, aber schwache Korrelation unter den exprimierten endogenen Hypoxiemarkern. Das Ausmaß der Nekrose korrelierte negativ mit den Spiegeln der exprimierten endogenen Hypoxiemarker. Die immunhistologische Doppelmarkierung mit GLUT-1 und MIB-1 ergab, dass etwa 20% der MIB- 1-positiven Tumorzellen in der Umgebung nekrotischer Bereiche kein GLUT-1 bildeten.Schlussfolgerung:Nekrose beeinflusst die Expression endogener Hypoxiemarker. Einige hypoxische Tumorzellen, die keine Hypoxiemarker exprimieren, können klonogen bleiben und die Behandlungsergebnisse beeinflussen. Empfohlen wird die Anwendung einer Kombination von Hypoxiemarkern, da deren Expression auch durch Hypoxie-unabhängige Faktoren beeinflusst wird.

Pancreas: imaging diagnosis with color/power Doppler ultrasonography, endoscopic ultrasonography, and intraductal ultrasonography

Recent advances of ultrasound imaging have made possible to depict various diseases and conditions of the pancreas. Color/power Doppler ultrasonography, endoscopic ultrasonography, and intraductal ultrasonography are feasible to show vascular abnormalities, differentiate the solid and cystic tumors, decide tumor extent, and help to perform interventional treatments of the pancreatic diseases. Those techniques will contribute to the more precise and easier diagnosis and to prompt decision of the treatments of the pancreatic disorders. Radiologists should recognize the diagnostic feasibility and limitations of those techniques in order to avoid unnecessary examinations on the patients, and obtain precise diagnostic images.

Results and DVH analysis of late rectal bleeding in patients treated with 3D-CRT or IMRT for localized prostate cancer

In patients undergoing radiotherapy for localized prostate cancer, dose–volume histograms and clinical variables were examined to search for correlations between radiation treatment planning parameters and late rectal bleeding. We analyzed 129 patients with localized prostate cancer who were managed from 2002 to 2010 at our institution. They were treated with 3D conformal radiation therapy (3D-CRT, 70 Gy/35 fractions, 55 patients) or intensity-modulated radiation therapy (IMRT, 76 Gy/38 fractions, 74 patients). All radiation treatment plans were retrospectively reconstructed, dose–volume histograms of the rectum were generated, and the doses delivered to the rectum were calculated. Time to rectal bleeding ranged from 9–53 months, with a median of 18.7 months. Of the 129 patients, 33 patients had Grade 1 bleeding and were treated with steroid suppositories, while 25 patients with Grade 2 bleeding received argon plasma laser coagulation therapy (APC). Three patients with Grade 3 bleeding required both APC and blood transfusion. The 5-year incidence rate of Grade 2 or 3 rectal bleeding was 21.8% for the 3D-CRT group and 21.6% for the IMRT group. Univariate analysis showed significant differences in the average values from V65 to V10 between Grades 0–1 and Grades 2–3. Multivariate analysis demonstrated that patients with V65 ≥ 17% had a significantly increased risk (P = 0.032) of Grade 2 or 3 rectal bleeding. Of the 28 patients of Grade 2 or 3 rectal bleeding, 17 patients (60.7%) were cured by a single session of APC, while the other 11 patients required two sessions. Thus, none of the patients had any further rectal bleeding after the second APC session.

Brachytherapy for Oral Tongue Cancer: An Analysis of Treatment Results with Various Biological Markers

OBJECTIVE Low-dose-rate (LDR) brachytherapy is an effective treatment for tongue cancer. However, little is known about the biological mechanism underlying this therapy, characterized by delivery of continuous exposures of LDR irradiation. It is reported that lower microvessel density (MVD), lower Ki-67 index or higher expression of endogenous hypoxic markers such as carbonic CA IX and Glut-1 are related to the poor control of tumors treated with external irradiation. To elucidate the biological characteristics of LDR brachytherapy, we analyzed our results in cases of tongue cancer treated with LDR brachytherapy by using immunohistochemical stainings with antibodies against Ki-67 and MVD, Glut-1 and CA IX. METHODS The prognostic value of Ki-67 index, MVD and the expression of CA IX and Glut-1 was assessed in 68 tongue cancers treated with LDR brachytherapy. The specimens were taken from tongue cancers before radiation therapy and immunohistochemical staining was performed. RESULTS The local recurrence-free survival rates were significantly different between T1+T2 and T3 (P = 0.00067), but not between low and high Ki-67 indexes (P = 0.54), between low and high MVD (P = 0.071), low and high CA IX indexes (P = 0.062) or low and high Glut-1 indexes (P = 0.107). T stage, the size of the tumor was the only significant factor for local control in multivariate analyses (P = 0.0377). CONCLUSION LDR could overcome the radioresistence of non-cycling and hypoxic cells; however, we cannot draw firm conclusions due to the limited number of patients.

Relation between Ku80 and microRNA-99a expression and late rectal bleeding after radiotherapy for prostate cancer

BACKGROUND AND PURPOSE Late rectal bleeding is one of the severe adverse events after radiotherapy for prostate cancer. New biomarkers are needed to allow a personalized treatment. MATERIALS AND METHODS Four patients each with grade 0-1 or grade 2-3 rectal bleeding were randomly selected for miRNA array to examine miRNA expression in peripheral blood lymphocytes (PBLs). Based on results of miRNA array, 1 of 348 miRNAs was selected for microRNA assays. Then, expression of DNA-dependent protein kinase mRNA and miR-99a was analyzed in the PBLs of 97 patients. PBLs were exposed to 4Gy of X-ray ex-vivo. RESULTS In the discovery cohort, grade 2-3 rectal bleeding was significantly higher in the Ku80 <1.09 expression group compared with ⩾1.09 group (P=0.011). In radiation-induced expression of miR-99a, grade 2-3 rectal bleeding was significantly higher in the miR-99a IR(+)/IR(-) >0.93 group compared with ⩽0.93 group (P=0.013). Most patients with grade 2-3 rectal bleeding were in the group with low Ku80 and high miR-99a expression. In the validation cohort, similar results were obtained. CONCLUSION A combination of low Ku80 expression and highly-induced miR-99a expression could be a promising marker for predicting rectal bleeding after radiotherapy.

Analysis of local control in patients with non-Hodgkin's lymphoma according to the WHO classification.

Purpose:To analyze the influence of radiotherapy doses, chemotherapy doses, and clinical parameters on in-field disease control to assess the optimal radiation doses for treatment of non-Hodgkin’s lymphoma according to the newly proposed WHO classification.Patients and Methods:Subjects consisted of 35 extranodal marginal-zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type, 75 diffuse large B-cell lymphomas (DLBCL), 14 follicular lymphomas, 17 extranodal natural killer (NK)/T-cell lymphomas, nasal type, eight unclassified peripheral T-cell lymphomas, four anaplastic large-cell lymphomas, T/null cell type, and five others. 59 patients received radiotherapy alone. 98 patients received CHOP, modified CHOP, or more intensive chemotherapy, and six patients were treated with other combination.Results:No patients with MALT lymphoma had in-field local recurrence. There were no recurrences in DLBCL patients who received chemotherapy in which the doses of adriamycin were > 200 mg/m2, nor in DLBCL patients who were treated with > 45 Gy. Only nine of 15 patients with T-cell lymphoma treated with ≤ 50 Gy and three of five patients treated with > 50 Gy had local control. The dose of adriamycin had no influence on local control of T-cell lymphoma.Conclusion:T/NK-cell lymphomas were more radioresistant than B-cell lymphomas. The prognosis for peripheral T/NK-cell lymphomas is poor even when treated by irradiation combined with chemotherapy.Ziel:Untersuchung des Einflusses der Strahlungsdosis, Chemotherapie-Intensität und klinischer Parameter auf die Kontrolle lokalisierter Herde, um optimale Parameter für die Behandlung des Non-Hodgkin-Lymphoms gemäß der vor kurzem vorgeschlagenen WHO-Klassifikation zu ermitteln.Patienten und Methodik:In die Untersuchung einbezogen wurden 35 extranodale („marginal-zone“) B-Zell-Lymphome des Mukosa-assoziierten-Lymphom-(MALT-)Typs, 75 diffuse großzellige B-Zell-Lymphome (DLBCL), 14 follikuläre Lymphome, 17 extranodale Natürliche-Killer-(NK-)/T-Zell-Lymphome (Nasaltyp), 8 unklassifizierte periphere T-Zell-Lymphome, 4 anaplastische (großzellige) Lymphome (T/null-Zell-Typ) and 5 andere. 59 Patienten erhielten ausschließlich Strahlentherapie. 98 Patienten erhielten CHOP, CHOP modifiziert oder eine intensivierte Chemotherapie, und 6 Patienten wurden mit einer anderen Kombination behandelt.Ergebnisse:Bei keinem der MALT-Lymphom-Patienten kam es zu einem Lokalrezidiv. Rezidive traten weder bei DLBCL-Patienten auf, die Chemotherapie mit Adriamycin in Dosierungen > 200 mg/m2 erhalten hatten, noch bei DLBCL-Patienten, die mit > 45 Gy behandelt worden waren. Nur bei 9 von 15 T-Zell-Lymphom-Patienten, die mit ≤ 50 Gy, und bei 3 von 5 Patienten die mit > 50 Gy behandelt worden waren, wurde eine lokale Kontrolle erreicht. Die Adriamycin-Dosis beeinflusste die lokale Kontrolle von T-Zell- Lymphomen nicht.Schlussfolgerungen:T/NK-Zell-Lymphome zeigten sich strahlungsresistenter als B-Zell-Lymphome. Die Prognose peripherer T/NK-Zell-Lymphome ist selbst bei Kombination von Strahlen- und Chemotherapie schlecht.

Hyperfractionated Accelerated Radiotherapy for T1,2 Glottic Carcinoma

Background and Purpose:Hyperfractionated accelerated radiotherapy without a split (AF) has been performed to improve the local control probability of early glottic carcinomas since 1990 in the authors’ institution. Here, they report their experience treating early glottic cancer patients with AF in a single institution who have a long follow-up period.Patients and Methods:131 T1 N0 M0 glottic cancers and 65 T2 N0 M0 glottic cancers were treated with conventional fractionation (CF) from 1984 to 1989 and with AF since 1990. CF consisted of five daily fractions of 2 Gy per week, to a total dose of 64 Gy. AF consisted of 1.72 Gy per fraction, two fractions per day, 5 days a week, to a total dose of 55 or 58.5 Gy.Results:The 5-year local control probability for T1 tumors was 94% with 58.5 Gy and 87% with 55 Gy of AF, whereas it amounted to 80% with CF. For T2 tumors, it was 56% with 58.5 Gy and 68% with 55 Gy of AF, whereas it amounted to 64% with CF. The data of T2 should be evaluated with caution due to the small number of patients. Patients with AF had more severe mucosal reactions but no severe late reactions.Conclusion:AF significantly improved the local control rates for T1 glottic cancer.Hintergrund und Ziel:Die hyperfraktionierte akzelerierte Strahlentherapie ohne Bestrahlungspause (AF) wird durchgeführt, um die lokale Kontrolle früher Glottiskarzinome zu verbessern. In diesem Beitrag geht es um die Erfahrung bei der AF-Behandlung von Patienten mit frühen Glottiskarzinomen in einer einzelnen Institution mit langen Nachuntersuchungszeiträumen.Patienten und Methodik:196 Glottiskarzinome (131 T1 N0 M0 und 65 T2 N0 M0) wurden zwischen 1984 und 1989 mit konventioneller Fraktionierung (CF) und seit 1990 mit AF behandelt. Die CF bestand aus fünf täglichen Fraktionen von 2 Gy pro Woche an 5 Tagen pro Woche bis zu einer Gesamtdosis von 64 Gy. Die AF bestand aus 1,72 Gy pro Fraktion, zwei Fraktionen pro Tag, 5 Tage pro Woche, bis zu einer Gesamtdosis von 55 oder 58 Gy.Ergebnisse:Die lokale 5-Jahres-Kontrollrate für T1-Tumoren betrug mit 58,5 Gy AF 94% und mit 55 Gy AF 87%, während sie mit CF bei 80% lag. Für T2-Tumoren betrug sie mit 58,5 Gy AF 56% und mit 55 Gy AF 68%, während sie mit CF bei 64% lag. Die T2-Daten sollten wegen der geringen Patientenzahl mit Vorsicht beurteilt werden. Patienten mit AF wiesen schwerere mukosale Reaktionen, jedoch keine schweren Spätkomplikationen auf.Schlussfolgerung:Die AF stellt eine signifikante Verbesserung der lokalen Kontrollrate für T1-Glottiskarzinome dar.

Hyperfractionated accelerated radiotherapy for T1,2 glottic carcinoma. Consideration of time-dose factors.

Background and Purpose:Hyperfractionated accelerated radiotherapy without a split (AF) has been performed to improve the local control probability of early glottic carcinomas since 1990 in the authors’ institution. Here, they report their experience treating early glottic cancer patients with AF in a single institution who have a long follow-up period.Patients and Methods:131 T1 N0 M0 glottic cancers and 65 T2 N0 M0 glottic cancers were treated with conventional fractionation (CF) from 1984 to 1989 and with AF since 1990. CF consisted of five daily fractions of 2 Gy per week, to a total dose of 64 Gy. AF consisted of 1.72 Gy per fraction, two fractions per day, 5 days a week, to a total dose of 55 or 58.5 Gy.Results:The 5-year local control probability for T1 tumors was 94% with 58.5 Gy and 87% with 55 Gy of AF, whereas it amounted to 80% with CF. For T2 tumors, it was 56% with 58.5 Gy and 68% with 55 Gy of AF, whereas it amounted to 64% with CF. The data of T2 should be evaluated with caution due to the small number of patients. Patients with AF had more severe mucosal reactions but no severe late reactions.Conclusion:AF significantly improved the local control rates for T1 glottic cancer.Hintergrund und Ziel:Die hyperfraktionierte akzelerierte Strahlentherapie ohne Bestrahlungspause (AF) wird durchgeführt, um die lokale Kontrolle früher Glottiskarzinome zu verbessern. In diesem Beitrag geht es um die Erfahrung bei der AF-Behandlung von Patienten mit frühen Glottiskarzinomen in einer einzelnen Institution mit langen Nachuntersuchungszeiträumen.Patienten und Methodik:196 Glottiskarzinome (131 T1 N0 M0 und 65 T2 N0 M0) wurden zwischen 1984 und 1989 mit konventioneller Fraktionierung (CF) und seit 1990 mit AF behandelt. Die CF bestand aus fünf täglichen Fraktionen von 2 Gy pro Woche an 5 Tagen pro Woche bis zu einer Gesamtdosis von 64 Gy. Die AF bestand aus 1,72 Gy pro Fraktion, zwei Fraktionen pro Tag, 5 Tage pro Woche, bis zu einer Gesamtdosis von 55 oder 58 Gy.Ergebnisse:Die lokale 5-Jahres-Kontrollrate für T1-Tumoren betrug mit 58,5 Gy AF 94% und mit 55 Gy AF 87%, während sie mit CF bei 80% lag. Für T2-Tumoren betrug sie mit 58,5 Gy AF 56% und mit 55 Gy AF 68%, während sie mit CF bei 64% lag. Die T2-Daten sollten wegen der geringen Patientenzahl mit Vorsicht beurteilt werden. Patienten mit AF wiesen schwerere mukosale Reaktionen, jedoch keine schweren Spätkomplikationen auf.Schlussfolgerung:Die AF stellt eine signifikante Verbesserung der lokalen Kontrollrate für T1-Glottiskarzinome dar.