Hisayasu Nagakura

High-dose-rate versus low-dose-rate intracavitary therapy for carcinoma of the uterine cervix: a randomized trial.

This was a prospective randomized clinical trial undertaken at our institution to compare low‐dose‐rate (LDR) intracavitary radiation therapy versus high‐dose‐rate (HDR) intracavitary radiation therapy for the treatment of cervical carcinoma.

Prognostic factors of nasopharynx tumors investigated by MR imaging and the value of MR imaging in the newly published TNM staging

PURPOSE To examine the usefulness of MR imaging for predicting local control of nasopharyngeal carcinoma (NPC) and the value of MR imaging in the newly published fifth edition of the TNM classification. METHODS AND MATERIALS We studied 29 patients with NPC with MR imaging and CT before and after treatment. Staging was done according to the fourth and newly published fifth editions of the International Union Against Cancer (UICC) staging system. The radiotherapy protocol was designed to deliver 66 to 68 Gy to the primary tumor and clinically involved nodes. RESULTS MR proved better than CT at identifying obliteration of the pharyngobasilar fascia, invasion of the sinus of Morgagni, through which the cartilaginous portion of the eustachian tube and the levator veli palatini muscle pass, invasion of the skull base, and metastases to lymph nodes in the carotid and retropharyngeal spaces. All seven patients without invasion of the pharyngobasilar fascia had local control. The local control rates of patients with invasion of the skull base were not good (60 to 73%). There was no apparent relationship between tumor volume determined by T1-weighted MR images and local control when the tumor volume was more than 20 cc. The newly published N staging system appears to successfully identify the high-risk group for distant metastasis as N3. In our series, four of five patients with N3 disease developed distant metastases. CONCLUSION Deep infiltration of the tumor is a more important prognostic factor in NPC than tumor volume. Since the newly published T staging system requires a search for tumor invasion into soft tissue such as parapharyngeal space and bony structures, MR imaging may be indispensable for the newly published NPC staging system.

Treatment of Lethal Midline Granuloma Type Nasal T-Cell Lymphoma

Nasal T-cell lymphoma of the LMG type (LMG-NTL) is characterized by progressive, unrelenting ulceration, and necrosis of the nasal cavity and midline facial tissues. The clinical behavior of this tumor in 16 patients is compared with that of a nasal lymphoma of non-LMG-NTL type (non-LMG-NTL) in 8 patients and a paranasal sinus lymphoma (PSL) in 6 patients. All patients had stage I or II disease. Fourteen of the 16 patients with LMG-NTL received chemotherapy before and/or after radiotherapy. Cause-specific 5-year survival rates for patients with LMG-NTL, non-LMG-NTL, and PSL were 22%, 75%, and 67% respectively. Seven patients with LMG-NTL, had complete response, although 3 recurred, whereas it was incomplete in 9 patients. The data indicates that it is desirable to deliver 50 Gy or more to achieve in-field control of LMG-NTL.

Radiation therapy for superficial esophageal cancer: a comparison of radiotherapy methods

PURPOSE A comparison of treatment outcomes in response to various methods of radiotherapy for superficial esophageal cancer (SEC) was carried out for a large series of patients. METHODS AND MATERIALS During the period from March 1987 to November 1998, 147 patients with superficial esophageal cancer received definitive radiation therapy at nine radiotherapy institutions in Japan. Fifty-five patients were treated with external radiation therapy alone, 69 with high-dose-rate intracavitary radiation therapy with or without external radiation therapy, and 23 with low-dose-rate intracavitary radiation therapy and external radiation therapy. RESULTS The 5-year survival rates for mucosal and submucosal cancer patients were 62% and 42%, respectively. The 5-year cause-specific survival rates for mucosal and submucosal cancer patients were 81% and 64%, respectively (p = 0.013). There was no statistically significant difference in the survival rates for either mucosal or submucosal cancer patients between treatment groups. Metastasis was observed only in submucosal cancer patients. Esophageal ulcers developed only in patients who received intracavitary radiation therapy, and were especially common in patients treated with a fraction size of 5 Gy or more. CONCLUSIONS The use of intracavitary radiation therapy does not influence the survival or local control rate of SEC. Optimal radiotherapy methods for SEC should be determined by a randomized clinical trial.

Radiotherapy for Kimura's disease: the optimum dosage.

PURPOSE To evaluate retrospectively the optimum dosage of irradiation for Kimuras disease. METHODS AND MATERIALS Twenty patients with Kimuras disease were treated with radiotherapy. The sex ratio was 19 males to 1 female. The mean ages at onset, initial treatment, and radiotherapy were 26.2, 29.5, and 32.2 years, respectively. Radiotherapy was mainly applied for residual or recurrent tumors. The eosinophil count increased by more than 10% in 18 of the 20 patients. In most instances, irradiation was given through a single field with dosages ranging from 20 to 44 Gy. RESULTS At the completion of radiotherapy, a marked response in tumor size was noted in all cases. The minimum follow-up was 48 months. Local control was obtained in 23 of 31 lesions (74.1%). At dosages of < or =25 Gy, 26-30 Gy, and > 30 Gy, local control was obtained in 2 of 8 (25.0%), 9 of 10 (90.0%), and 12 of 13 sites (92.3%), respectively. CONCLUSIONS Radiotherapy is an effective treatment for Kimuras disease. This strongly suggests that no surgical procedure other than a biopsy should be carried out. The radiation field should be limited to the lesion and swelling of the adjacent lymph nodes as much as possible, with a optimum dosage of 26-30 Gy regardless of tumor size.

Radiotherapy of Vertebral Hemangiomas

Between 1975 and 1996, 14 patients (11 females, 3 males) with vertebral hemangioma received treatment with radiotherapy. Thirteen patients had a history of back pain or lumbago and 2 patients had neurological symptoms such as sensory impairment or paraplegia. The standard dose administered was 36 Gy in 18 fractions (five treatments per week). In the 13 patients with pain, this was completely or partially relieved. The condition of a man with hypesthesia of the legs deteriorated and a woman with paraplegia who was treated with decompressive laminectomy followed by radiotherapy recovered completely after irradiation. CT scan before irradiation showed thickened trabeculae as small punctate areas of sclerosis in all patients. At MR imaging before irradiation, T2-weighted MR images showed areas of high intensity in all patients and MR images demonstrated lesion enhancement. However, none of the patients who were treated successfully with radiation demonstrated any changes of the affected vertebra in the conventional radiographic films. CT scan or MR imaging, even 5 years after irradiation. Radiological imaging is indispensable for the diagnosis of vertebral hemangiomas but does not appear to be useful for evaluating the effects of radiotherapy.

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.

ACCELERATED RADIOTHERAPY FOR T1, 2 GLOTTIC CARCINOMA: ANALYSIS OF RESULTS WITH KI-67 INDEX

PURPOSE Hyperfractionated and accelerated radiotherapy without a split was performed to improve the local control probability of early glottic carcinomas. We analyzed the results of this regimen by using the Ki-67 index. METHODS AND MATERIALS Over a 12-year period, 85 T1N0M0 glottic cancers and 50 T2N0M0 glottic cancers were treated with conventional fractionation (CF) from 1984 to 1989 and with accelerated fractionation (AF) since 1990. The CF program consisted of five daily fractions of 2 Gy per week, for a total of 64 Gy. The AF program consisted of 1.72 Gy per fraction, two fractions per day, 5 days a week, for a total of 55 or 58 Gy. The specimens, taken before radiotherapy, were immunohistochemically stained with anti-Ki-67 antibody. RESULTS The 5-year local control probability for T1 tumors was 79.6 +/- 6.9% with CF treatment, whereas with AF it was 86.9 +/- 5.6%. For T2 tumors it was 62.7 +/- 12.2% with CF, whereas it was 74.7 +/- 7.8% with AF. The difference between CF and AF did not reach the point of statistical significance. However, when T1 tumors had a Ki-67 index lower than 50%, the local control rate achieved with AF was significantly better than that with CF (p = 0.018). When the tumors had a Ki-67 index that was 50% or more, there was no difference in the local control rate between CF and AF, whether they were T1 or T2. The peak mucosal reactions at the larynx and/or hypopharynx were much more severe and appeared at smaller doses and earlier in AF than in CF. The patients with AF showed no severe late complications. CONCLUSIONS AF could not obtain statistically significant improvement in local control probability of T1 or T2 glottic carcinomas.

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.

EBM-based Clinical Guidelines for Pancreatic Cancer (2013) Issued by the Japan Pancreas Society: A Synopsis

Clinical practice guidelines for pancreatic cancer based on evidence-based medicine (2006) were published by the Japan Pancreas Society (Committee for revision of clinical guidelines for pancreatic cancer) in March 2009 in Japanese, revised to Clinical Practice Guidelines for Pancreatic Cancer based on evidence-based medicine (2009) in July 2009 in Japanese and further revised to Clinical Practice Guidelines for Pancreatic Cancer (2013) in October 2013 in Japanese. These guidelines were established according to evidence-based medicine. A total of 629 papers were collected from among 4612 reports concerning pancreatic cancer listed in PubMed and Igakuchuo Zasshi between May 2007 and January 2011. This new set of guidelines was written by members of the Committee for the Revision of Clinical Practice Guidelines for Pancreatic Cancer in the Japan Pancreas Society. The guidelines provide an algorithm for the diagnosis (Fig. 1) and treatment (Fig. 2) of pancreatic cancer and address six subjects (Diagnosis, Surgery, Adjuvant therapy, Radiation therapy, Chemotherapy and stent therapy), with 35 clinical questions and 57 recommendations.