Masahiko Oguchi

Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2010 for the treatment of colorectal cancer

Colorectal cancer is a major cause of death in Japan, where it accounts for the largest number of deaths from malignant neoplasms among women and the third largest number among men. Many new methods of treatment have been developed during recent decades. The Japanese Society for Cancer of the Colon and Rectum Guidelines 2014 for treatment of colorectal cancer (JSCCR Guidelines 2014) have been prepared as standard treatment strategies for colorectal cancer, to eliminate treatment disparities among institutions, to eliminate unnecessary treatment and insufficient treatment, and to deepen mutual understanding among health-care professionals and patients by making these guidelines available to the general public. These guidelines have been prepared as a result of consensuses reached by the JSCCR Guideline Committee on the basis of careful review of evidence retrieved by literature searches and taking into consideration the medical health insurance system and actual clinical practice in Japan. They can, therefore, be used as a guide for treating colorectal cancer in clinical practice. More specifically, they can be used as a guide to obtaining informed consent from patients and choosing the method of treatment for each patient. As a result of the discussions of the Guideline Committee, controversial issues were selected as clinical questions, and recommendations were made. Each recommendation is accompanied by a classification of the evidence and a classification of recommendation categories, on the basis of consensus reached by Guideline Committee members. Here we present the English version of the JSCCR Guidelines 2014.

Phase I/II Study of Concurrent Chemoradiotherapy for Localized Nasal Natural Killer/T-Cell Lymphoma: Japan Clinical Oncology Group Study JCOG0211

PURPOSE To explore a more effective treatment for localized nasal natural killer (NK)/T-cell lymphoma, we conducted a phase I/II study of concurrent chemoradiotherapy. PATIENTS AND METHODS Treatments comprised concurrent radiotherapy (50 Gy) and 3 courses of dexamethasone, etoposide, ifosfamide, and carboplatin (DeVIC). Patients with a newly diagnosed stage IE or contiguous IIE disease with cervical node involvement and a performance status (PS) of 0 to 2 were eligible for enrollment. The primary end point of the phase II portion was a 2-year overall survival in patients treated with the recommended dose. RESULTS Of the 33 patients enrolled, 10 patients were enrolled in the phase I portion and a two thirds dose of DeVIC was established as the recommended dose. Twenty-seven patients (range, 21 to 68; median, 56 years) treated with the recommended dose showed the following clinical features: male:female, 17:10; stage IE, 18; stage IIE, 9; B symptoms present, 10; elevated serum lactate dehydrogenase, 5; and PS 2, 2. With a median follow-up of 32 months, the 2-year overall survival was 78% (95% CI, 57% to 89%). This compared favorably with the historical control of radiotherapy alone (45%). Of the 26 patients assessable for a response, 20 (77%) achieved a complete response, with one partial response. The overall response rate was 81%. The most common grade 3 nonhematologic toxicity was mucositis related to radiation (30%). No treatment-related deaths were observed. CONCLUSION Concurrent chemoradiotherapy using multidrug resistance-nonrelated agents and etoposide is a safe and effective treatment for localized nasal NK/T-cell lymphoma and warrants further investigation.

Radiotherapy for extranodal, marginal zone, B-cell lymphoma of mucosa-associated lymphoid tissue originating in the ocular adnexa: a multiinstitutional, retrospective review of 50 patients.

Due to the small number of patients and differences in the pathologic classification in most radiotherapy series, information regarding the adequacy of tumor control in patients with ocular‐adnexal marginal zone B‐cell lymphoma of mucosa‐associated lymphoid tissue (MALT lymphoma) is limited.

Late toxicity after definitive concurrent chemoradiotherapy for thoracic esophageal carcinoma.

PURPOSE To evaluate late cardiopulmonary toxicities after concurrent chemoradiotherapy (CCRT) for esophageal carcinomas. METHODS AND MATERIALS From February 2002 through April 2005, 74 patients with clinical Stage I-IVB carcinoma of the esophagus were treated with CCRT. Sixty-nine patients with thoracic squamous cell carcinoma were the core of this analysis. Patients received 60 Gy of radiation therapy in 30 fractions over 8 weeks, including a 2-week break, and received 2 cycles of fluorouracil/cisplatin chemotherapy concomitantly. Initial radiation fields included primary tumors, metastatic lymph nodes, and supraclavicular, mediastinal, and celiac nodes areas. Late toxicities were assessed with the late radiation morbidity scoring scheme of the Radiation Therapy Oncology Group/European Organiation for Research and Treatment of Cancer. RESULTS The median age was 67 years (range, 45-83 years). The median follow-up time was 26.1 months for all patients and 51.4 months for patients still alive at the time of analysis. Five cardiopulmonary toxic events of Grade 3 or greater were observed in 4 patients, Grade 5 heart failure and Grade 3 pericarditis in 1 patient, and Grade 3 myocardial infarction, Grade 3 radiation pneumonitis, and Grade 3 pleural effusion. The 2-year cumulative incidence of late cardiopulmonary toxicities of Grade 3 or greater for patients 75 years or older was 29% compared with 3% for younger patients (p = 0.005). CONCLUSION The CCRT used in this study with an extensive radiation field is acceptable for younger patients but is not tolerated by patients older than 75 years.

Is postoperative radiotherapy for thymoma effective

OBJECTIVE The authors determined the effect of postoperative mediastinal irradiation in preventing local and pleural recurrence of thymoma. SUMMARY BACKGROUND DATA The role of mediastinal irradiation after incomplete resection or biopsy of an invasive thymoma is well established. However, routine use of adjuvant mediastinal irradiation for patients with thymoma after complete resection remains controversial. METHODS During the 19-year period from 1973 to 1992, operations were performed on 89 patients with thymoma. Of these 89 patients, 80 patients who underwent gross complete tumor resection including adjacent tissues that appeared to be invaded by tumor were selected for this study. The effects of postoperative mediastinal irradiation on the recurrence rate of thymoma were analyzed according to histologic type, clinical stage, and whether adhesions to or invasion of the pleura or pericardium were present. RESULTS Recurrence of thymoma was observed in 13 of 80 (16.3%) patients. No recurrence was observed in 23 patients with noninvasive thymoma. In patients with invasive thymoma whose tumor was macroscopically adherent to the pleura but not microscopically invasive (p1), recurrence was observed in 4 of 11 patients (36.4%) when mediastinal irradiation was not performed, but in none of 10 patients who received mediastinal irradiation. However, in patients with microscopic pleural invasion (p2), a high recurrence rate was observed with mediastinal irradiation (40%, 6/15 patients) or without mediastinal irradiation (30%, 3/10 patients). Postoperative mediastinal irradiation for patients with microscopical invasion to pericardium (c2) did not decrease the recurrence rate. Analysis of the mode of recurrence showed that mediastinal irradiation may have been effective in preventing local recurrence, but it did not control the pleural dissemination that was observed in 12 of 13 recurrent cases. CONCLUSIONS Mediastinal irradiation is not necessary for patients with noninvasive thymoma. In patients with invasive thymoma, postoperative mediastinal irradiation is effective in preventing recurrence in patients with p1 thymoma, but not in patients with p2 or c2 tumors. Further adjuvant therapy should be performed to supplement mediastinal irradiation in patients with p2 or c2 thymoma, even after complete resection.

Phase II study of concurrent chemoradiotherapy with high-dose-rate intracavitary brachytherapy in patients with locally advanced uterine cervical cancer: Efficacy and toxicity of a low cumulative radiation dose schedule ☆

OBJECTIVE A multicenter phase II trial was conducted to assess the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) with high-dose-rate intracavitary brachytherapy (HDR-ICBT) using a low cumulative prescribed dose schedule in patients with locally advanced uterine cervical cancer. METHODS The Japanese Gynecologic Oncology Group (JGOG) study JGOG1066 enrolled patients with FIGO stages III-IVA uterine cervical cancer who had no para-aortic lymphadenopathy (>10 mm) assessed by CT. Patients received definitive radiotherapy (RT) consisting of external beam whole pelvic RT and HDR-ICBT. The cumulative linear quadratic equivalent dose (EQD2) was 62-65 Gy prescribed at point A. Cisplatin 40 mg/m(2) weekly was administered concurrently with RT for 5 courses. RESULTS Of the 72 patients registered, 71 were eligible. With a median follow-up of 28 months, the 2-year progression-free survival rate and pelvic disease progression-free rate were 66% (95% CI, 54% to 76%) and 73% (95% CI, 61% to 82%), respectively. Progression-free survival decreased significantly with increased central tumor size (P=0.036). The 2-year cumulative late complication rates were 24% for all grades, 9% for grade 1, 12% for grade 2, 3% for grade 3, and 0 for grades 4/5. CONCLUSIONS The JGOG1066 demonstrated that CCRT using HDR-ICBT with a low cumulative RT dose schedule achieved comparable outcome as those achieved with global dose schedules (EQD2=85 Gy) with a lower incidence of late toxicity for locally advanced uterine cervical cancer in a Japanese population.

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.

Clinicopathologic study of 53 metaplastic breast carcinomas: their elements and prognostic implications

Metaplastic carcinoma of the breast is a relatively rare cancer and includes various histologic types. In this cancer, metaplastic elements are heterogeneous and sometimes mixed. We investigated, by histopathologic means, these elements and clinical implications that could indicate the clinical course (including the prognosis). Fifty-three metaplastic breast carcinoma cases and their prognoses were investigated by initially examining the presence or absence of spindle-cell elements, and then the presence or absence of other elements. Spindle cells were classified as high or low grade. The number of spindle-cell-positive cases was 24 (45%) of 53. The 24 spindle-cell (+) cases were subdivided into 12 high-grade (HGsp) (distant metastatic rate per 100 person-years, 13.27) and 12 low-grade (LGsp) (0.00) patients. Spindle-cell (-) cases were subdivided into 22 pure squamous cell carcinomas (5.93) and 7 matrix-producing carcinomas (0.00). There were significant differences among the 4 groups with regard to the disease-free period (P = .0081, log-rank test). The distant metastatic risks in the HGsp and pure squamous cell carcinomas groups were significantly higher than that in the matrix-producing carcinoma + LGsp group (nonmetastatic groups) after controlling for the effects of tumor size and lymph node metastasis (P = .019 and P = .016, respectively, Poisson regression model). The presence of high-grade spindle cells was related to the prognosis, and some histologic subtypes may be important with respect to the prognosis. The presence of high-grade spindle cells in metaplastic breast carcinoma may indicate aggressive behavior.

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.

TUMOR BULK AS A PROGNOSTIC FACTOR FOR THE MANAGEMENT OF LOCALIZED AGGRESSIVE NON-HODGKIN'S LYMPHOMA: A SURVEY OF THE JAPAN LYMPHOMA RADIATION THERAPY GROUP

PURPOSE To identify the prognostic factors that specifically predict survival rates of patients with localized aggressive non-Hodgkins lymphoma (NHL). METHODS AND MATERIALS The survey was carried out at 25 radiation oncology institutions in Japan in 1998. The 5-year event-free (EFS) and overall survival rates (OAS) were calculated, and univariate and multivariate analyses were done to identify which of the following factors, namely, gender, age, performance status (PS), serum lactate dehydrogenase (LDH) level, Stage (I vs. II), tumor bulk (maximum diameter), and treatment, were significant from the viewpoint of prognosis. RESULTS A total of 1141 patients with Stage I and II NHL were treated by the Japanese Lymphoma Radiation Therapy Group between 1988 and 1992. Of them, 787 patients, who were treated using definitive radiotherapy with or without chemotherapy for intermediate- and high-grade lymphomas in working formulation, constituted the core of this study. Primary tumors arose mainly from extranodal organs (71%) in the head and neck (Waldeyers ring: 36% and sinonasal cavities: 9%). The factors associated with poorer prognosis were age over 60 years old (p < 0. 0001), radiation therapy alone (p < 0.0001), PS = 2-4 (p = 0.0011), (sex male, p = 0.0078), a bulky tumor more than 6 cm in maximum diameter (p = 0.0088), elevated LDH (p = 0.0117), and stage II (p = 0.0642). A median dose of 42 Gy was delivered mainly to the involved fields. Short-course chemotherapy was provided in 549 (70%) patients. The 5-year OAS and EFS rates for all patients were 71% and 67%, respectively. According to the stage-modified International Prognostic Index, the 5-year EFS of the patients with risk factors from 0 to 1 was 76%, 61% for patients with two risk factors, and 26% for patients with three or more risk factors. CONCLUSION Extranodal presentation, especially Waldeyers ring and sinonasal cavities, is encountered more frequently in Japan than in Western countries. Tumor bulk is an important prognostic factor in patients with localized aggressive extranodal NHL. Short course chemotherapy followed by radiation therapy was associated with prolonged survival in patients with localized aggressive NHLs of extranodal origin and 0-1 risk factor.