Intracavitary Radiation Therapy for Recurrent Cystic Brain Tumors with Holmium-166-Chico : A Pilot Study

OBJECTIVE: Intracavitary injection of beta-emitting radiation source for control of cystic tumors has been tried with a benefit of localized internal radiation. The authors treated cystic brain tumor patients with Holmium-166-chitosan complex (Ho-166-chico), composed of a beta-emitting radionuclide Holmium-166 and biodegradable chit polymer, and evaluated the safety and effective measurement for response. METHODS: Twenty-two patients with recurrent cystic brain tumor and/or located in a deep or eloquent area were enrolled in this pilot study. The cyst volume and wall thickness were determined on CT or MRI to assess radiological response. The activity of Ho-166-chico injected via Ommaya reservoir was prescribed to be 10-25 Gy to the cyst wall in a depth of 4 mm. RESULTS: There was neither complications related to systemic absorption nor leakage of Ho-166-chico in all 22 patients. But, two cases of oculomotor paresis were observed in patients with recurrent craniopharyngioma. Radiological response was seen in 14 of 20 available follow-up images (70%). Seven patients of 'evident' radiological response experienced more than 25% decrease of both cyst volume and wall thickness. Another 7 patients with 'suggestive' response showed decrease of cyst volume without definitive change of the wall thickness or vice versa. All patients with benign tumors or low grade gliomas experienced symptomatic improvement. CONCLUSION: Ho-166-chico intracavitary radiation therapy for cystic tumor is a safe method of palliation without serious complications. The determination of both minimal effective dosage and time interval of repeated injection through phase 1 trial could improve the results in the future.

Relationship between 252Cf neutron ray intracavitary irradiation and esophageal carcinoma extensive infiltration on CT / 中华放射医学与防护杂志

Objective To explore the relationship between esophageal carcinoma extensive infiltration and lesion length and 252 Cf intracavitary brachytherapy,and to evaluate its prognostic influence.Methods Thirty-two patients with esophageal carcinoma were treated by external beam and 252Cf intracavitary radiation.The patients were first treated with conventional fractionated radiation to a dose of 38 Gy over 4 weeks,with 5 daily fractions of 2 Gy per week,and then treated with external and intracavitary radiation concomitantly (4.0 Gy per fraction,once a week on every Saturday to 12 Gy in 3 fractions).The total dose of external irradiation was 50 Gy.Results The local control rate (LCR) at 1,3 and 5 years was 93.75％,76.70％ and 65.75％ in the patients with ≤5 cm lesion (NMT5 group),and 60.94％,27.08％ and 27.08％ in the patients with ＞5 cm lesion (MT5 group),respectively (x2 =7.01,P ＜ 0.05).The 1-,3-and 5-year survival rate (SR) was 93.75％,56.25％ and 43.75％ in the NMT5 group,and 75.00％,18.75％,12.50％ in the MT5 group,respectively (x2 =5.96,P ＜ 0.05).The LCR at 1,3 and 5 years was 92.31％,73.85％ and 61.54％ in the patients with ≤1.5 cm infiltration depth (NMT1.5 group),and 67.67％,35.45％ and 35.45％ in the patients with ＞ 1.5 cm infiltration depth (MT1.5 group),respectively (x2 =3.87,P ＜ 0.05).The 1-,3-and 5-year SR was 92.31％,61.54％ and 46.15％ in the NMT1.5 group,and 73.68％,21.05％ and 15.79％ in the MT1.5 group,respectively (x2 =6.24,P ＜ 0.05).LCR and SR in the patients with ≤5 cm lesion and ≤2 cm infiltration depth were significantly better than those with ＞ 5 cm lesion and ＞ 2 cm infiltration depth (x2 =10.09,7.97,P ＜ 0.05).Conclusions The patients with ≤5 cm lesion length or those with ≤ 1.5 cm infiltration depth,might become the most adaptable indication for 252 Cf intracavitary radiation.In addition,those patients with ≤2 cm infiltration depth and ≤5 cm lesion length were also suitable for 252Cf intracavitary radiation.

Prognostic factors for primary vaginal carcinoma managed with radiotherapy : a study of 83 cases / 中华放射肿瘤学杂志

Objective To analyze the clinical and histopathologic characteristics and prognostic factors for primary carcinoma of the vagina managed with radiotherapy at a single institution . Methods Eighty-three patients with primary vaginal carcinoma were treated with definitive radiation therapy between 1980 and 2007 were retrospectively analyzed. Radiotherapy was delivered with external beam radiation alone in 11 patients, intracavitary after-loading radiation alone in 7 patients, and external beam combined with After-loading radiation in 65 patients. The median radiation dose was 75 Gy. Fifty-one patients received more than 75 Gy. Thirty-one patients received combined chemotherapy. Of them, 16 received intravenous neoadjuvant or adjuvant chemotherapy, 8 received intra-arterial chemotherapy and 7 received concomitant chemotherapy. Patients were staged acoording to FIGO staging system. Nineteen patients had stage Ⅰ ;31 had stage Ⅱ, 25 had stage Ⅲ and 8 had stage Ⅳ diseases. Fifty-three patients had squamous cell carcinoma, 22 had adenocarcinoma, 2 had adenosquamous cell carcinoma,3 had papillary serous carcinoma,2 had clear-cell carcinoma and 1 had undifferentiated carcinoma. Thirty-nine patients had grade 1 and 44 had grade 2 and/or grade 3 diseases. Results The follow-up rate was 89%. Thirty-five and 31 patients had minimum followed-up time of 3 and 5 years respectively. The 3-and 5-year overall survival rates were 51% and 42% respectively. Univariate analysis showed that FIGO stage ( x2 = 11.30,P= 0. 010), histopathology type (x2=5.76,P=0.016),pathologic grade (x2=5.76,P=0.016), tumor size (x2=4.81,P=0. 020), tumor site ( x2=23.50,P =0. 000), external beam combined with intracavitary irradiation ( x2 =29. 76,P =0. 000) correlated with overall survival rate. Cox multivariate analysis showed only FIGO stage ( x2 = 5.93, P = 0. 015 ) and tumor size ( x2 = 8.48, P= 0. 004 ) were independent prognostic factors affecting overall survival. Serious complications were developed in 12% ( 10/83 ) of the patients. One patient suffered from vesicovaginal fistula and 3 from rectovaginal fistula. Twenty-eight patients had local or distant relapses, and the 3-year overall survival rate was 14% after salvage therapy. Conclusions Radiotherapy is effective for early stage primary vaginal carcinoma. FIGO stage and tumor size were independent prognostic factors affecting overall survival. The role of chemotherapy for advanced disease needs further study.

Rectal Complication Following Radical Radiotherapy in Carcinoma of the Uterine Cervix / 대한방사선종양학회지

PURPOSE: This study evaluated the late rectal complications in cervix cancer patients following treatment with external beam radiotherapy (EBRT) and high dose rate intracavitary radiation (HDR ICR). The factors affecting the risk of developing late rectal complications and its incidence were analyzed and discussed. MATERIALS AND METHODS: The records of 105 patients with cervix cancer who were treated with radical radiotherapy using HDR ICR between July, 1995 and December, 2001 were retrospectively reviewed. The median dose of EBRT was 50.4 Gy (41.4~56.4 Gy) with a daily fraction size of 1.8 Gy. A total of 5~7 (median: 6) fractions of HDR ICR were given twice weekly with a fraction size of 4~5 Gy (median: 4 Gy) to A point using an Ir (Iridium)-192 source. The median dose of ICR was 24 Gy (20~35 Gy). During HDR ICR, the rectal dose was measured in vivo by a semiconductor dosimeter. The median follow-up period was 32 months, ranging from 5 to 84 months. RESULTS: Of the 105 patients, 12 patients (11%) developed late rectal complications; 7 patients with grade 1 or 2, 4 patients with grade 3 and 1 patient with grade 4. Rectal bleeding was the most frequent chief complaint. The complications usually began to occur 5~32 (median: 12) months after the completion of radiotherapy. Multivariate analysis revealed that the measured cumulative rectal BED over 115 Gy3 (Deq over 69 Gy) and the depth (D) of a 5 Gy isodose volume more than 50 mm were the independent predictors for late rectal complications. CONCLUSION: With evaluating the cumulative rectal BED and the depth of a 5 Gy isodose volume as predictors, we can individualize treatment planning to reduce the probability of late rectal complications.

Study of Patient's Position to Reduce Late Complications in High Dose Rate Intracavitary Radiation of the Uterine Cervix Cancer / 대한방사선종양학회지

PURPOSE: Radiation proctitis and radiation cystitis are frequent and problematic late complications in patients treated with radiation for the uterine cervix cancer. Authors tried to find out the better patient's position in high dose rate intracavitary radiation to reduce the radiation dose of bladder and rectum. MATERIALS AND METHODS: In 13 patients, Foley catheters were inserted to patients' bladder and rectum and were ballooned with radioopaque dye. After insertion of a tandem and two ovoids, semi-orthogonal anteroposterior and lateral films were taken in both lithotomy and supine position. The rectal point and bladder point were defined according to the criteria recommended in the ICRU Report 38 with modification. Using these films, all patients' bladder and rectal dose were calculated in both positions (the radiation dose of A point was set to 400 cGy). And also, the distance of bladder and rectum from uterine cervical os was calculated in both positions. RESULTS: The average radiation dose of rectum was 240.7 cGy in lithotomy position and 278.3 cGy in supine position, and the average radiation dose of bladder was 303.5 cGy in lithotomy position and 255.8 cGy in supine position. After the paired t-test, the radiation dose of rectum in lithotomy position was marginally significantly lower than that in supine position, while the radiation dose of bladder in lithotomy position was significantly higher than that in supine position. On the other hand, the average distance between rectum and cervical os was 35.2 mm in lithotomy position and 32.3 mm in supine position. and the average distance between bladder and cervical os was 30.4 mm in lithotomy position and 34.0 mm in supine posi-tion. After the paired t-test, the distance between rectum and cervical os in lithotomy position was significantly longer than that in supine position, while the distance between bladder and cervical os in lithotomy position was significantly shorter than that in supine position. CONCLUSION: The radiation dose of bladder can be reduced in supine position and the radiation dose of rectum can be reduced in lithotomy position, so we can choose appropriate position in each patient.

Beta Dosimetry in Intraperitoneal Administration of 166Ho-chitosan Complex / 대한핵의학회잡지

Intraperitoneal adminstration of radioisotopes is suggested to treat the metastatic ovarian cancer in the pertioneal cavity. Administering beta-emitting radioisotopes into the pertioneal cavity allows the maximum energy delivery to the cancerous cells of the pertioneal wall surface while sparing the normal cells located in deep site of the peritoneal wall. In this study, dose estimates of the peritoneal wall are provided to be used for prescribing the amount of 166Ho-chitosan complex administered. The 166Ho-chitosan complex diffused in the peritoneal fluid may attach to the peritoneal wall surface. The attachment fraction of 166Ho-chitosan complex to the peritoneal wall surface is obtained by simulating the ascites with Fischer rats. Both volume source in the peritoneal fluid and the surface source over the peritoneal wall surface are counted for the contribution to the peritoneal wall dose. The Monte Carlo code EGS4 is used to simulate the energy transfer of the beta particles emitted from 166Ho. A plane geometrical model of semi-infinite volume describes the peritoneal cavity and peritoneal wall. A semi-infinite plane of 10 micrometer in thickness at every 1 mm of depth in the peritoneal wall is taken as the target in dose estimation. Greater han 98 percents of attachment fraction has been observed from the experiments with Fischer rats. Given 1.3 microcurie/cm2 and 2.4 microcurie/ml of uniform activity density, absorbed dose is 123 Gy, 8.59 Gy, 3.00 Gy, 1.03 Gy, and 327 Gy at 0 mm, 1 mm, 2 mm, 3 mm, and 4 mm in depth to the peritoneal wall, respectively.

Late Rectal Complication in Patients Treated with High Dose Rate Brachytherapy for Stage IIB Carcinoma of the Cervix / 대한치료방사선과학회지

PURPOSE: This paper reports a dosimetric study of 88 patients treated with a combination of external radiotherapy and high dose rate ICR for FIGO stage IIB carcinoma of the cervix. The purpose is to investigate the correlation between the radiation doses to the rectum. external radiation dose to the whole pelvis. ICR reference volume. TDF, BED and the incidence of late rectal complications, retrospectively METHODS AND MATERIALS: From November 1989 through December 1992, 88 patients with stage IIB cervical carcinoma received radical radiotherapy at Department or Radiation Oncology in Yonsei University Hospital. Radiotherapy consisted of 44-54 Gy(median 49 Gy) external beam irradiation plus high dose rate intracavitary brachy therapy with 5 Gy per fraction twice a week to a total dose of 30 Gy on point A. The maximum dose to the rectum by contrast(r,R) and reference rectal dose by ICRU 38(dr, DR) were calculated. The ICR reference volume was calculated by Gamma Dot 3.11 HDR planning system, retrospectively. The time-dose factor(TDF) and the biologically effective dose (BED) were calculated. RESULTS: Twenty seven(30.7%) of the 88 patients developed late rectal complications : 12 patients(13.6%) for grade 1, 12 patients(13.6%) for grade 2 and 3 patients(3.4%) for grade 3. We found a significant correlation between the external whole pelvis irradiation dose and grade 2, 3 rectal complicaition. The mean dose to the whole pelvis for the group of patients with grade 2, 3 complication was higher, 4093.3+/-453.1 cGy, than that for the patients without complication 3873.8+/-415.6 (0.05p<0.1). The gradual increase in the frequency of grade 2, 3 rectal compication increased as a function of the dose of external beam therapyto the whole pelvis(midline shielding start dose) and total rectal dose. The mean total rectal dose by rectal barium(R) for the group of patients with grade 2, 3 rectal complication was higher, 7163.0+/-838.5 cGy, than that for the patients without rectal complication, 6772.7+/-884.0(p<0.05). There was no correlation of the rate of grade 2, 3 rectal complication with the ICR rectal doses(r,dr), ICR reference volume, TDF and BED. CONCLUSION: This investigation has revealed a significant correlation between the dose calculated at the rectal dose by ICRU 38(DR) or the most anterior rectal dose by contrast(R), dose to the whole pelvis and the incidence of grade 2,3 late rectal complications in patients with stage IIB cervical cancer undergoing external beam radiotherapy and HDR ICR. Thus there rectal reference points doses and whole pelvis dose appear to be useful prognostic indicators of late rectal complication in high dose rate ICR treatment in cervical carcinoma.

The Results of Radiation Therapy Alone vs Radiation Plus Chemotherapy of Uterine Cervix Cancer / 대한치료방사선과학회지

PURPOSE: Radiation therapy(RT) is conventionally standard treatment for locally advanced stage for uterine cervix cancer. Recently to improve treatment results, combined chemotherapy and radiation therapy was tried. We retrospectively analysed our experience of 122 patients. Comparision of the results in 45 patients treated with RT alone and 77 patients treated with RT plus chemotherapy was made. MATERIALS AND METHODS: from January 1985 to December 1991, 122 patients with cervix cancer were treated with whole pelvic external RT and ICR(34 1 ICR, 77 2 ICR, 11 high dose rate ICR) in our department. Forty five patients were treated with RT alone, and 77 patients were treated with combined plus chemotherapy. Mean age was 58 eyars(range:29-81). Histologic types were 111 squamous cell carcinoma, large cell carcinoma, 3 adenocarcinoma, and 2 adenosquamous cell carcinoma. According to the FIGO stage 6 had stage IA94.9%, 11 had IIA(9.0%), 37 had IIB(30.3%), 3 had IIA(2.5%), 63 had IIB(51.6%), and 2 had stage IV(1.6%). In 77 patients with RT plus chemotherapy, 36 patients were treated with VBP(vinblastin, bleoycin, cisplainum), 39 patients with cisplatinum plus 5-FU and 2 patients with 5-FU. RESULTS: Complete response after external RT(3960cGy-5500cGy)was achieved in 61 patients(50%). He actuarial 5 year and 9 year survival rate was 57.8% and 53.9%, respectively. Five year actuarial survival rate was 63.1% with RT alone(n=45) and 55.9% with RT plus chemotherapy(n=77). Ther 5 year survival rate was 35.5% for 1 course of ICR and 67% for 2 courses of ICR. There was statistically significant advantage of survival with RT alone group who wre treated with 2 coursed of ICR and dose to the A point> or=8000cGy(4/25 died). In RT plus chemotherapy group, dose response was not seen and there was no differnce in 5 year survival between 1 course and 2 course of ICR(50% vs 56.8%), and dose to point A less than 8000cGy and more than 8000 cGy(55.6% vs 55.7%). There was no significant difference in survival between RT alone and RT plus chemotherapy for patients with tumor size greater than 3cm in size. Five year survival rate for early stage (Stage IB and IIA) with RT alone group and with RT plus chemotherapy group was 60% and 77.0%, respectively. In advanced stage (stage IIB, IIIA, IIIB, IVA) the 5 year actuarial survival rate were 62.6%, for RT alone group vs 53.6 for RT plus chemotherapy group. CONCLUSION: Present study demonstrates that there is no survival advantage with adding chemotherapy in advanced stage of uterine cervix cancer. RT alone is considered as treatment of choice for patients with locally advanced cervix cancer. There was increased survival in RT alone group treated with RT dose above 8000 cGy to point A and 2 course of ICR, but 2 course of ICR and RT dose above 8000 cGy to point A did not affect survival advantage in RT plus chemotherapy group.

The Rofe of High Dose Rate(HDR) Intracavitary Radiation Therapy for the Management of Nasopharyngeal Carcinoma / 대한치료방사선과학회지

From September 1989 to June 1992, 22 patients with nasopharyngeal carcinoma were treated in Asan Medical Center with an external beam of 60 Gy followed by a boost dose of 15 Gy HDR brachytherapy. There were 5 females and 17 males with median age of 44 years (range: 20-69 years). All patients were histologically confirmed and staged by physical examination, CT scan and/or MRI. By the AJCC TNM staging system, there were 2 patients with stage II (T2NO), 4 with stage III(T3NO, T1-3N1), and 16 with stage IV(T4 or N2-3). Four patients received chemotherapy with 5-FU and cisplatin prior to radiotherapy. All patients were followed up periodically by a telescopic examination and radiologic imaging study of CT scan or MRI with a median follow-up time of 13 months (range: 3-34 mouths). Twenty ore patients showed a complete response one month after completing therapy and one patient showed a complete response after three months. At the time of this analysis, seventeen patients remain alive without evidence of disease, but four patients developed distant metastasis and one patient died a month after treatment. The local control rate was 100% in a median follow-up time of 13 months. The two year overall and disease free survival rates by the Kaplan-Meier method were 94% and 67%, respectively. Serious radiation sequelae have not been observed yet. Although longer follow-up is needed, this retrospective analysis suggests that HDR brachytherap given as a boost therapy for nasoharyngeal carcinoma may improve the local control. To reduce the incidence of distant metastasis, we need to develop a more effective systemic chemotherapy.

The Results of Curative Radiation Therapy for 49 Patients of the Uterine Cervical Carcinomas / 대한치료방사선과학회지

Fifty patients with carcinoma of the uterine cervix received curative radiotherapy by external irradiation of the whole pelvis and intracavitary radiation at the Department of Therapeutic Radiology, Kangnam St. Mary's Hospital from September,1983 to October, 1986. External beam whole pelvic irradiation was done first up to 4500-5940 cGy in 5 weeks to 6.5 weeks, followed by an intracavitary radiation. Total dose of radiation to point A varied from 6500 cGy to l1344 cGy (average 6764 cGy). Of the 50 patients, one patient was lost to follow up and follow up period of the remaining 49 patients ranged from 3 months to 93 months (median 32 months). According to FIGO classification, 6 (12.2%) were in stage Ib, 6(12.2%) in stage Ia, 25 (51%) in stage IIb, 7 (14%,) in stage III, and 5 (10.2%) in stage IV. Age of the patients ranged from 33 to 76 years (Median 60 years). Pathologically, fourty six(94%) patients had squamous cell carcinoma, 2 (4% had adenocarcinoma, and 1 (2%) had adenosquamous cell carcinoma. Overall response rate was 84%. 5-year survival rate was 49% for entire group (75% for stage Ib, 83% for Stage IIa, 42.5% for stage IIb, 25% for stage III, 40% for stage IV). Complications were observed in 11(22.4%) patients, who revealed rectal complications with most common frequency. Others were self limiting trifle ones such as wet desquamation, fatigue, mild leukopenia, etc. The correlation of the survival rate with various factors (age, dose, Hb level, pelvic Iymph node status, performance status, local recurrence) was evaluated but showed no statistical significance except the age and local recurrence in this series; survival of patients less than 50 years of age was worse than that of the older, and the presence of local recurrence had worse prognosis(p< 0.05).