Ichiro Ogino

Late rectal complication following high dose rate intracavitary brachytherapy in cancer of the cervix.

PURPOSE To examine the incidence of radiation-induced late rectal complications using a rectal reference point in patients with cancer of the uterine cervix. METHODS AND MATERIALS The subjects were 253 patients with cancer of the cervix who underwent high dose rate intracavitary brachytherapy (HDR-ICR). The rectal point (RP) was defined according to the criteria recommended in the ICRU Report 38. The time-dose factor (TDF) and the biologically effective dose (BED) were calculated as components of the cumulative reference rectal dose using the rectal reference point dose in intracavitary brachytherapy combined with the external whole pelvis dose. RESULTS Statistical comparison of factors affecting the incidence of late rectal complication was conducted using data for 161 patients. The incidence of late rectal complications in the 161 patients was 9 patients (5.6%) for grade 1, 51 patients (31.7%) for grade 2, 11 patients (6.8%) for grade 3, and 13 patients (8.1%) for grade 4. The TDF and BED values were significantly correlated with the incidence of late rectal complication, and also showed strong correlation (r = 0.976) with each other. Grade 4 rectal complication was not observed in any patients with TDF below 130 or BED below 147. The calculated incidence of complications ranged from 5 to 10% at TDF values from 104 to 124 and at BED values from 119 to 146. CONCLUSION These data regarding the incidence of rectal complication may be useful in reducing the incidence of late rectal complications arising after HDR-ICR treatment of cervical uterine cancer by adjusting the dose per fraction and number of fractions of HDR-ICR in individual patients and by improving the technique of inserting the intracavitary radiation apparatus.

Pelvic insufficiency fractures in postmenopausal woman with advanced cervical cancer treated by radiotherapy.

PURPOSE To assess the predisposing factors and clinical characteristics of pelvic insufficiency fractures (PIF) in postmenopausal women with pelvic irradiation. MATERIAL AND METHODS A total 335 postmenopausal patients with cervical cancer of the intact uterus treated with radiation therapy between 1983 and 1998 were reviewed. Total external dose was delivered between 45 and 50.4 Gy with parallel opposed anteroposterior portals. Total brachytherapy dose at point A was delivered between 10 and 36 Gy. PIF were diagnosed by bone scintigraphy and confirmed by computed tomography. The cumulative incidence of symptomatic PIF was estimated by actuarial methods. Potential risk factors (age, weight, type II diabetes, delivery, menopause, total external dose, total brachytherapy dose) were assessed. RESULTS Fifty-seven (17.0%) of 335 patients were diagnosed as having PIF. Forty-seven patients were symptomatic and ten were asymptomatic. Parameters carrying a significant association with PIF were body weight 49 kg or below (P=0.044) in stepwise logistic regression analysis. The cumulative incidence of symptomatic PIF at 5 years was 17.9% calculated by the Kaplan-Meier method. A body weight of 49 kg or below and more than three deliveries were identified as having a significant effect on symptomatic PIF in univariate analysis (P=0.021, P=0.003, log-rank test) and Cox life table regression analysis (P=0.038, P=0.013). Five patients required narcotic agents and eight patients required hospital admission. CONCLUSIONS We should consider reducing the dose contribution to the sacrum and sacroilac joints, without underdosing the tumor, especially in postmenopausal women with many deliveries or low body weight.

Reduction of Prostate Motion by Removal of Gas in Rectum During Radiotherapy

PURPOSE To evaluate the prostate and seminal vesicle motion in patients during both simulation and radiotherapy by rectal gas removal. METHODS AND MATERIALS A total of 34 patients were treated in a whole pelvic radiotherapy (WPRT) arm and 42 patients in a non-WPRT arm. Of the 76 patients, 42 (26 in the non-WPRT arm and 16 in the WPRT arm) were instructed to insert their index finger and wash their rectums to evacuate their rectal gas. In addition to the planning computed tomography scan, three subsequent computed tomography scans were obtained during RT. The organs were outlined on each computed tomography image. Changes in the position of the prostate and seminal vesicles were analyzed using the center of mass (COM) coordinate system. The time trend, overall variations, systematic variations, and random variations were analyzed. RESULTS The average cross-sectional area in the rectal gas removal group was significantly smaller than in all patients and in the WPRT arm. The vector of the prostate and seminal vesicle displacement for the rectal gas removal group was significantly smaller than in all patients. With rectal gas removal, the 95% confidence limit of the prostate displacement vector was reduced by 2.3 mm in the non-WPRT arm and 2.9 mm in the WPRT arm. The 95% confidence limit of the seminal vesicle displacement vector was reduced by 0.3 mm in the non-WPRT arm and 4.4 mm in the WPRT arm. CONCLUSIONS Using rectal gas removal, the cross-sectional area could be decreased, resulting in reduced motion and margins for the prostate and seminal vesicles. This is especially important for WPRT patients who require RT to the prostate, seminal vesicles, and pelvic lymph nodes.

FDG-PET scanning after radiation can predict tumor regrowth three months later.

PURPOSE Positron emission tomography (PET) with 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) is well known for providing excellent clinical information regarding malignant tumors. We investigated whether dual-time FDG-PET performed immediately post radiation could predict early regrowth of malignant tumors. MATERIALS AND METHODS Twenty patients with malignant tumors were included in this study. All patients received radiation, and each underwent FDG-PET before the initiation of therapy and within 10 days of completing their course of irradiation. PET images after irradiation were obtained at 60 min and 180 min post FDG injection. For 26 lesions in 20 patients, standardized uptake value (SUV) before and after treatment was calculated and then correlated with postradiation tumor response and outcome at 3 months status post irradiation. RESULTS Retention index [RI = (SUV on delayed image - SUV on early image)/SUV on early image] after irradiation showed a significant difference between patients with residual tumor and those without residual tumor at 3 months status post irradiation (p < 0.0025). All 9 lesions in 6 patients with residual tumors showed more than 0.1 of RI, whereas none of the lesions with less than 0.1 of RI revealed residual tumors. CONCLUSIONS Dual-time FDG-PET imaging just after irradiation is potentially useful for predicting early regrowth of malignant tumors.

Role of Radiotherapy as Curative Treatment of Extramammary Paget’s Disease

PURPOSE Extramammary Pagets disease (EMPD) is a relatively rare malignancy that usually arises in the genital areas. Wide surgical excision remains the standard and most reliable curative treatment of EMPD. However, surgery is sometimes not possible, because many patients are elderly, and complete excision can be difficult owing to the tumor location. We, therefore, performed a review to determine the role of radiotherapy (RT) for EMPD. METHODS AND MATERIALS A total of 22 patients with EMPD in their external genitalia (4 men and 18 women, age 52-94 years at RT) underwent RT with curative intent. Nine patients had regional lymph node metastases. A total dose of 45-70.2 Gy (median, 60) was delivered to the pelvis, including the tumors, in 25-39 fractions (median, 33). RESULTS In all but 3 patients, the irradiated tumors were controlled during a follow-up period of 8-133 months (median, 42). Of the 22 patients, 13 developed recurrences, including local progression within the radiation field in 3 and lymph node and/or distant metastases outside the radiation field in 10, at 3-43 months after treatment. The 2- and 5-year local progression-free rates were 91% and 84%, respectively. Of the 22 patients, 7 patients had died at 33-73 months after RT. The cause of death was tumor progression in 4, infectious pneumonia in 2, and renal failure in 1 patient. The overall and cause-specific survival rates were 100% for both at 2 years and 53% and 73% at 5 years, respectively. No therapy-related Grade 3 or greater toxicity was observed. CONCLUSIONS RT is safe and effective for patients with EMPD. It appears to contribute to prolonged survival as a result of good tumor control.

Noninvasive and Curative Radiation Therapy for Sebaceous Carcinoma of the Eyelid

PURPOSE Sebaceous carcinoma of the eyelid is a rare malignancy. Surgical excision remains the standard and most reliable curative treatment. However, surgery is sometimes not possible because many patients are elderly, and it frequently causes functional and cosmetic impairment of the eyelid. We therefore carried out a study to determine the role of radiation therapy in relation to sebaceous carcinoma of the eyelid. METHODS AND MATERIALS Thirteen patients with sebaceous carcinoma of the eyelid underwent radiation therapy with curative intent. There were 6 men and 7 women, and their ages at irradiation ranged from 60 to 85 years (median, 78 years). Only 1 patient had cervical lymph node metastasis, and none of the patients had distant metastasis. A total dose of 50 to 66.6 Gy (median, 60 Gy) was delivered to tumor sites in 22 to 37 fractions. RESULTS All irradiated tumors were controlled at a median follow-up period of 55 months. Only 1 patient had recurrence of cervical lymph node metastasis outside the radiation field, at 22 months after irradiation. The 5-year local progression-free and disease-free rates were 100% and 89%, respectively. The overall and disease-free survival rates at 5 years were 100% and 89%, respectively. Although acute and transient therapy-related reactions of Grade 2 or less were observed, there were no severe toxicities of Grade 3 or greater. CONCLUSIONS Radiation therapy is a safe and effective treatment for patients with sebaceous carcinoma of the eyelid. It appears to contribute to prolonged survival as a result of good tumor control, and it also facilitates functional and cosmetic preservation of the eyelid.

Analysis of prognostic factors in stage IIB–IVA cervical carcinoma treated with radiation therapy: Value of computed tomography

PURPOSE To define the influence of the tumor size measured by computed tomography (CT) and lymph node involvement detected by CT in patients treated with radiation therapy for Stage IIB-IVA carcinoma of intact uterine cervix. METHODS AND MATERIALS This was a retrospective analysis of 233 patients with uterine cervical cancer managed with both external irradiation and high-dose-rate intracavitary brachytherapy (HDR-ICR) at Kanagawa Cancer Center. The results were analyzed for the end points of absolute survival (AS), disease-free survival (DFS), pelvic control (PC), and central control (CC). The parameters of stage, CT-measured anterior-posterior (AP) cervix size, and CT-detected lymph node metastases were evaluated using univariate and multivariate analysis. RESULTS The stage, AP cervix size, and lymph node involvement were significant pretreatment factors in univariate analysis with respect to AS, DFS, PC, and CC. Multivariate analysis confirmed that significant risk was associated with certain prognostic parameters. Those in terms of AS, in order of decreasing significance, were lymph node involvement, AP cervix size, age, and total HDR-ICR dose. When DFS was studied, lymph node involvement and AP cervix size were demonstrated to have a significant effect. Stage and lymph node involvement significantly affected PC. CONCLUSION Because the International Federation of Gynecological Obstetrics staging system fails to incorporate important prognostic information about tumor volume and lymph node involvement, CT-detected lymph node metastases as well as CT-measured cervix size should be determined as complementary additional prognostic measures.

Treatment Effects and Sequelae of Radiation Therapy for Orbital Mucosa-Associated Lymphoid Tissue Lymphoma

PURPOSE Among extranodal lymphomas, orbital mucosa-associated lymphoid tissue (MALT) lymphoma is a relatively rare presentation. We performed a review to ascertain treatment efficacy and toxicity of radiation therapy for orbital MALT lymphoma. We also evaluated changes in visual acuity after irradiation. METHODS AND MATERIALS Thirty patients with orbital MALT lymphoma underwent radiation therapy with curative intent. Clinical stages at diagnosis were stage IEA in 29 patients and stage IIEA in 1 patient. Total doses of 28.8 to 45.8 Gy (median, 30 Gy) in 15 to 26 fractions (median, 16 fractions) were delivered to the tumors. RESULTS All irradiated tumors were controlled during the follow-up period of 2 to 157 months (median, 35 months) after treatment. Two patients had relapses that arose in the cervical lymph node and the ipsilateral palpebral conjunctiva outside the radiation field at 15 and 67 months after treatment, respectively. The 5-year local progression-free and relapse-free rates were 100% and 96%, respectively. All 30 patients are presently alive; the overall and relapse-free survival rates at 5 years were 100% and 96%, respectively. Although 5 patients developed cataracts of grade 2 at 8 to 45 months after irradiation, they underwent intraocular lens implantation, and their eyesight recovered. Additionally, there was no marked deterioration in the visual acuity of patients due to irradiation, with the exception of cataracts. No therapy-related toxicity of grade 3 or greater was observed. CONCLUSIONS Radiation therapy was effective and safe for patients with orbital MALT lymphoma. Although some patients developed cataracts after irradiation, visual acuity was well preserved.

High-dose-rate Intracavitary Brachytherapy Combined with External Beam Radiotherapy for Stage IIIb Adenocarcinoma of the Uterine Cervix in Japan: A Multi-Institutional Study of Japanese Society of Therapeutic Radiology and Oncology 2006–2007 (Study of JASTRO 2006–2007)

OBJECTIVE The current study was a retrospective questionnaire survey of stage IIIb adenocarcinoma of the uterine cervix treated with high-dose-rate intracavitary brachytherapy combined with external beam radiation therapy in Japan aimed to investigate the optimal dose on the basis of the biological effective dose and prognostic factors. METHODS Between 1990 and 2000, 61 patients with stage IIIb adenocarcinoma of the uterine cervix underwent high-dose-rate intracavitary brachytherapy combined with external beam radiation therapy in 19 major hospitals in Japan. This retrospective questionnaire survey was performed by mail including survey charts to be fulfilled by radiation oncologists in these 19 major hospital. Fifty had only adenocarcinoma components and 11 had adenosquamous cell carcinoma components. All patients were treated with high-dose-rate intracavitary brachytherapy combined with external beam radiation therapy. Total biological effective dose (T-BED(10)) was calculated from the sum of the biological effective doses of the external beam radiation therapy and the intracavitary brachytherapy. Thirty-two patients underwent chemotherapy. RESULTS The 5-year overall survival rate of all patients was 20.2%. Stratified by total biological effective dose, the 5-year overall survival rate was 0% for T-BED(10) <75 Gy, 24.7% for T-BED(10) between 75 and 100 Gy and 0% for T-BED(10) >110 Gy (P = 0.15). Stratified by histopathology, the 5-year overall survival rate was 22.1% for adenocarcinoma and 13.6% for adenosquamous cell carcinoma (P = 0.43). Stratified by chemotherapy, the 5-year overall survival rate was 20.3% in patients who received chemotherapy and 20.4% in patients who did not receive chemotherapy (P = 0.96). CONCLUSIONS The 5-year overall survival rate of stage IIIb adenocarcinoma of the uterine cervix in this retrospective questionnaire survey was 20.2%. The optimal T-BED(10) and evident prognostic factors were not clear from this questionnaire survey.

Treatment Outcomes, Growth Height, and Neuroendocrine Functions in Patients With Intracranial Germ Cell Tumors Treated With Chemoradiation Therapy

PURPOSE We carried out a retrospective review of patients receiving chemoradiation therapy (CRT) for intracranial germ cell tumor (GCT) using a lower dose than those previously reported. To identify an optimal GCT treatment strategy, we evaluated treatment outcomes, growth height, and neuroendocrine functions. METHODS AND MATERIALS Twenty-two patients with GCT, including 4 patients with nongerminomatous GCT (NGGCT) were treated with CRT. The median age at initial diagnosis was 11.5 years (range, 6-19 years). Seventeen patients initially received whole brain irradiation (median dose, 19.8 Gy), and 5 patients, including 4 with NGGCT, received craniospinal irradiation (median dose, 30.6 Gy). The median radiation doses delivered to the primary site were 36 Gy for pure germinoma and 45 Gy for NGGCT. Seventeen patients had tumors adjacent to the hypothalamic-pituitary axis (HPA), and 5 had tumors away from the HPA. RESULTS The median follow-up time was 72 months (range, 18-203 months). The rates of both disease-free survival and overall survival were 100%. The standard deviation scores (SDSs) of final heights recorded at the last assessment tended to be lower than those at initial diagnosis. Even in all 5 patients with tumors located away from the HPA, final height SDSs decreased (p = 0.018). In 16 patients with tumors adjacent to the HPA, 8 showed metabolic changes suggestive of hypothalamic obesity and/or growth hormone deficiency, and 13 had other pituitary hormone deficiencies. In contrast, 4 of 5 patients with tumors away from the HPA did not show any neuroendocrine dysfunctions except for a tendency to short stature. CONCLUSIONS CRT for GCT using limited radiation doses resulted in excellent treatment outcomes. Even after limited radiation doses, insufficient growth height was often observed that was independent of tumor location. Our study suggests that close follow-up of neuroendocrine functions, including growth hormone, is essential for all patients with GCT.