Comparison of split-course radiation therapy and continuous radiation therapy for unresectable bronchogenic carcinoma: 5 year results.

One hundred and eighty-eight patients with inoperable or unresectable bronchogenic carcinoma were stratified by cell type, TNM staging, and prior surgery and then randomized into two treatment groups: continuous radiation therapy and split-course radiation therapy. There was no difference in clinical or objective improvement in the two groups. Survival rates for cases of squamous cell carcinoma, small cell carcinoma, and adrenocarcinoma were the same after both regimens of therapy. Split-course therapy resulted in a significantly better survival rate in cases of large cell carcinoma but the number of cases was small. We doubt that the difference is clinically significant. Objective roentgenographic response was accompanied by improved survival in squamous cell carcinoma, but not in the other three cell types. Split-course radiation therapy is superior to continuous radiation therapy because it is better tolerated by the patient and because re-examination of the patient prior to the second half of split-course therapy permits the detection of new metastatic disease that has become manifest during the rest period and spares the patient the futile second half of radiation therapy.     

Preoperative radiation therapy in endometrial carcinoma: preliminary report of a clinical trial.

A total of 91 patients with stage I endometrial adenocarcinoma who were referred for radiation prior to hysterectomy were randomly allocated to recieve either intracavitary or external bean irradiation. Total abdominal hysterectomy was done 4-8 weeks later. The 53 patients who received intracavitary irradiation had an actuarial 5 year disease-free survival rate of 75%; the survival rate of the 38 patients in the external beam group was 48%. Nine patients in the external beam group had recurrence or metastases compared to two in the intracavitary group. These recurrences were predominantly pelvic. Complications were also more frequent in the external beam group. These results demonstrate that intracavitary radiation is superior to external beam radiation using the regiments described.     

Heavy particle radiotherapy at the University of California Lawrence Berkeley Laboratory. Clinical studies by the Northern California Oncology Group

At the university of California Lawrence Berkeley Laboratory, patients have been irradiated for 10 years with heavy ions (He, C, Ne, Si). Due to the biologic efficacy of this type of radiation as well as the possibility of a precise dose application, the tumors can be irradiated with very high doses without exposing the surrounding tissues. The experience gained in the treatment of more than 800 patients is presented. It shows that this radiation can be used to localize tumors situated near to particularly radiosensitive organs such as skull base, paraspinal region, and the eye.     

Potential therapeutic effects of contrast materials in hysterosalpingography: a prospective randomized clinical trial. Kaiser Permanente Infertility Work Group

PURPOSE: To evaluate the influence of the contrast material used in hysterosalpingography (HSG) on subsequent reproductive success, independent of other therapeutic interventions. MATERIALS AND METHODS: In a prospective, multisite, randomized trial, 666 women who had been infertile for more than 1 year and were scheduled to undergo HSG as part of their evaluation were assigned to one of three groups: those receiving water-soluble contrast material (WSCM) (n = 260), those receiving oil-soluble contrast material (OSCM) (n = 273), and those receiving both OSCM and WSCM (n = 133). Possible causes of infertility and therapeutic interventions were abstracted from the medical records. Data on conception within 1 year and the outcome of conception were ascertained from multiple sources. RESULTS: Of 666 women, 204 (30.6%) had at least one pregnancy, and 136 (20.4%) had live births. The rates of live births were 20.4% (54 of 260) after HSG with WSCM, 19.4% (53 of 273) after HSG with OSCM, and 21.8% (29 of 133) after HSG with both WSCM and OSCM. Differences in reproductive outcome among contrast material groups were not statistically significant ((chi2)8 = 6.08, P = .64). Whatever the cause of infertility, the use of different contrast materials led to no significant differences in the rates of live births. CONCLUSION: There is no evidence to suggest that the choice of contrast material affects the rate of term pregnancy.     

Combined therapy of oral cancer bleomycin and radiation: a clinical trial.

A concurrent randomised controlled clinical trial to evaluate a combination of Bleomycin and radiation as against radiation only in the treatment of advanced oral cancer has been conducted at the Cancer Institute, Madras, since 1971. All T3 and T4 previously untreated oral squamous cell carcinomas with N0, N1 and N2 regional nodes, or N3 nodes confined to the submandibular region, without systemic metastases or gross infiltration of the temporal and infratemporal fossa producing total trismus, and in decent general health were eligible for the trial. Patients with gross active pulmonary tuberculosis were excluded, as were recurrent carcinomas. Age, external fungation of growth or radiological bone invasion were no bar. Randomisation was done by the sealed envelope technique. The study group received concurrent fractionated cobalt 60 teletherapy using two opposing fields and 10-15 mg of Intra-arterial or Intravenous Bleomycin. The controls received fractionated cobalt teletherapy and i.v. or i.m. distilled water on the same protocol as the Bleomycin cases. All cases were evaluated double blind 8 weeks after the end of radiation therapy, and were classified as 'favourable response' or 'failure'. The criterion of 'favourable response' was 'total clinical healing of the tumour within the volume of irradiation with no subsequent recurrence within that volume, whatever the length of follow up'. Anything else was reported as a failure. A long term follow up of 3 years is also available. 136 cases have completed the trial. The favourable response in the study group was 77% as against 20.9% in the control group. The differential response is statistically significant. The present study is the fourth in the series of combined therapeutic trials conducted in advanced oral squamous cell carcinoma since 1958. (Krishnamurthi and Shanta, 1963, 1965, 1967 and 1971). A concurrent randomised controlled clinical trial to evaluate the combination of Bleomycin and radiation as against radiation only in treatment of advanced oral cancer has been conducted at the Cancer Institute, Madras since 1971.     

Case numbers for a randomized clinical trial of boron neutron capture therapy for Glioblastoma multiforme

Boron neutron capture therapy (BNCT) with Na₂B₁₂H₁₁SH (BSH) or p-dihydroxyborylphenylalanine (BPA), and with a combination of both, was compared to radiotherapy with temozolomide, and the number of patients required to show statistically significant differences between the treatments was calculated. Whereas arms using BPA require excessive number of patients in each arm, a two-armed clinical trial with BSH and radiotherapy plus temozolomide is feasible.     

Intensity-modulated radiation therapy for the spine at the University of California, Irvine.

Radiation treatment of malignant diseases of the spine poses unique challenges to the radiation oncology treatment team. Intensity-modulated radiation therapy (IMRT) offers the capability of delivering high doses to targets near the spine while respecting spinal cord tolerance. At the University of California, Irvine, 8 patients received a total of 10 courses to the spine for a variety of primary and metastatic malignant conditions. This paper discusses anatomical considerations, spinal cord radiation myelopathy, and treatment planning issues as it relates to the treatment of spinal cord lesions. Between October 1997 and August 2001, a total of 8 patients received 10 courses of IMRT for primary or metastatic disease of the spine. Cancers treated included metastatic lung, renal, adrenocortical cancers, and primary sarcomas and giant cell tumor. Five cases had 6 courses given for re-irradiation of symptomatic disease and 3 cases had 4 courses of IMRT as primary management of their spinal lesions. Although 3 courses were given postoperatively, these were for grossly residual disease. For the re-irradiation patients, the mean follow-up interval was 4 months. The local control was estimated at 14%. Of the patients treated with primary intent, the mean follow-up was 9 months and the local control rate 75%. No patients developed spinal cord complications.     

兆伏级锥形束CT图像引导放疗所致鼻咽癌患者剂量的探讨

目的 评价和估算兆伏级锥形束CT(MV CBCT)成像系统在图像引导放疗中所致鼻咽癌患者的辐射剂量。方法 选择MV CBCT系统头颈部8 MU扫描预案,利用0.65 cm³指型电离室和CT头部剂量体模测量出体模不同位置的吸收剂量。并利用XiO治疗计划系统模拟MV CBCT扫描过程,计算体模电离室测量点的吸收剂量和鼻咽癌患者肿瘤靶区及危及器官的吸收剂量。结果 体模不同位置吸收剂量的测量值和计算值具有很好的一致性,相对误差均小于3.5%。MV CBCT图像引导放疗所致鼻咽癌患者肿瘤靶区平均剂量为6.43 cGy,脑干、脊髓和视交叉的平均剂量分别为6.36 、6.83和6.90 cGy,左、右视神经平均剂量分别为7.70和7.53 cGy,左、右腮腺平均剂量分别为6.86和6.43 cGy。结论 使用治疗计划系统模拟MV CBCT图像采集过程估算剂量准确、可靠。在设计患者治疗计划时,要充分考虑MV CBCT图像采集过程所致患者剂量。     

Phase I/II trial of single-fraction high-dose-rate brachytherapy-boosted hypofractionated intensity-modulated radiation therapy for localized adenocarcinoma of the prostate

PurposeA Phase I/II protocol was conducted to examine the toxicity and efficacy of the combination of intensity-modulated radiation therapy (IMRT) with a single-fraction high-dose-rate (HDR) brachytherapy implant.Methods and MaterialsFrom 2001 through 2006, 26 consecutive patients were treated on the trial. The primary objective was to demonstrate a high rate of completion without experiencing a treatment-limiting toxicity. Eligibility was limited to patients with T stage ≤2b, prostate-specific antigen (PSA) ≤20, and Gleason score ≤7. Treatment began with a single HDR fraction of 6 Gy to the entire prostate and 9 Gy to the peripheral zone, followed by IMRT optimized to deliver in 28 fractions with a normalized total dose of 70 Gy. Patients received 50.4 Gy to the pelvic lymph node. The prostate dose (IMRT and HDR) resulted in an average biologic equivalent dose >128 Gy (α/β = 3). Patients whose pretreatment PSA was ≥10 ng/mL, Gleason score 7, or stage ≥T2b received short-term androgen ablation.ResultsMedian followup was 53 months (9–68 months). There were no biochemical failures by either the American Society of Therapeutic Radiology and Oncology or the Phoenix definitions. The median nadir PSA was 0.32 ng/mL. All the 26 patients completed the treatment as prescribed. The rate of Grade 3 late genitourinary toxicity was 3.8% consisting of a urethral stricture. There was no other Grade 3 or 4 genitourinary or gastrointestinal toxicities.ConclusionsSingle-fraction HDR-boosted IMRT is a safe effective method of dose escalation for localized prostate cancer.     

A prospective randomized study concerning to the point A dose in high-dose rate intracavitary radiation therapy for carcinoma of the uterine cervix.

From January 1983 through December 1987, a total of 138 patients with previously untreated carcinoma of the uterine cervix were entered into the prospective randomized study concerning the two different schedules of point A dose of remote afterloading high-dose rate intracavitary therapy (RALS) and external irradiation dose at the Center for Adult Diseases, Osaka. Group A consisted of 71 patients who were treated with fraction size of point A dose of 7.5 Gy and group B included 67 patients treated with fraction size of 6 Gy. According to the staging system of UICC (1978), 33 patients were classified into stage I, 50 patients stage II, 45 patients stage III, and ten patients stage IV. Three-year survival rates by stage and RALS schedule were in group A 80% and in group B 100% in stage I, 57% and 68% in stage II, 62% and 60% in stage III and 2/8 and 0/2 in stage IV. Survival curves showed no statistically significant difference in each stage. Late rectal and bladder complications requiring treatment (Kottmeier's grade 2 or more) after RALS developed 1.5% (2/138, group A none, group B two) and 1.5% (2/138, group A one, group B one), respectively. This result suggests that this trial is acceptable on survival as well as complication rates.     

Effects of low-dose cisplatin on 89Sr therapy for painful bone metastases from prostate cancer: a randomized clinical trial.

This study evaluated the effects of low-dose cisplatin plus 89Sr versus 89Sr alone in the treatment of painful bone metastases from prostate cancer, addressing both pain palliation and cytostatic effects. METHODS: Seventy patients with metastatic hormone-refractory prostate cancer were randomized into 2 groups: One group (arm A) received 148 MBq 89Sr plus 50 mg/m(2) cisplatin, and the other group (arm B) received 148 MBq 89Sr plus placebo. After treatment, the patients were followed up until death to evaluate the outcome variables: grade and duration of pain palliation, onset of new painful sites, changes in bone disease, global survival, serum prostate-specific antigen and alkaline phosphatase changes, and hematologic toxicity. RESULTS: Overall pain relief occurred in 91% of patients in arm A and 63% of patients in arm B (P < 0.01), with a median duration of 120 d in arm A and 60 d in arm B (P = 0.002). New painful sites on previously asymptomatic bone metastases appeared in 14% of patients in arm A and in 30% of patients in arm B (P = 0.18). The median survival without new painful sites was 4 mo in arm A and 2 mo in arm B (P = 0.04). Bone disease progression was observed in 27% of patients in arm A and in 64% of patients in arm B (P = 0.01). Median global survival after therapy was 9 mo in arm A and 6 mo in arm B (P = 0.30). Transient and moderate hematologic toxicity, as determined by World Health Organization criteria, was apparent in both arms without significant differences. CONCLUSION: The addition of a low dose of cisplatin enhances the effect of a standard dose of 89Sr without significant side effects, producing a significant improvement in pain palliation and a cytostatic effect on bone disease.     

Acute toxicity and cost analysis of a phase III randomized trial of accelerated and conventional radiotherapy for squamous carcinoma of the head and neck: a Trans-Tasman Radiation Oncology Group study

The primary purpose of the present analysis was to assess the feasibility and acute toxicity of a pure accelerated fractionation regimen in a cooperative group setting. This analysis included the first 320 patients entered on to the Trans-Tasman Radiation Oncology Group (TROG) randomized controlled trial which compared accelerated radiotherapy (ART) with conventional radiotherapy (CRT) in stage III and IV squamous cell carcinoma (SCC) of the head and neck. Patients were randomized to either 59.4 Gy in 33 fractions over 24 days (ART) or to 70 Gy 35 fractions over 49 days (CRT) after being stratified for site and stage. Accrual began in 1991 and the trial was closed on 3 April 1998 with the targeted 350 patients. The 3-year survival for the whole group was 54%, and the 3-year disease-free survival was 41%. Toxicity data were available on 303 patients (148 ART; 155 CRT). Mucosal toxicity was worse in the accelerated arm, and it peaked approximately 3 weeks earlier than the conventional arm. Skin toxicity was equivalent but occurred approximately 7 days earlier in the accelerated arm. Acute effects in both arms healed completely. Hospitalization was more common in the ART arm (71 vs 52 patients; P = 0.01) but the total bed days in hospital was not greatly different (1707 bed days for ART and 1607 bed days for CRT). Patients were more likely to require nasogastric (NG) feeding in the ART arm (49 vs 33 patients; P = 0.02). There were 1157 NG feeding days for ART and 1154 NG feeding days for CRT. The average cost of radiation treatment per patient including hospitalization, NG feeding and accommodation was $11,750 in the ART arm and $11,587 in the CRT arm. The accelerated arm has been shown to be a tolerable, practical and cost-equivalent regimen. The assessment of the therapeutic ratio of this accelerated protocol (ART) will be determined when the analysis of late effects and loco-regional control is made when the data are more mature.     

CT fluoroscopy-guided biopsy of the lung or upper abdomen with a breath-hold monitoring and feedback system: a prospective randomized controlled clinical trial

PURPOSE: To prospectively determine the clinical effectiveness of a breath-hold monitoring and feedback system in computed tomographic (CT) fluoroscopy-guided biopsies in which respiratory motion is a problem. MATERIALS AND METHODS: Institutional review board approval and oral and written informed consent were obtained. This study was HIPAA compliant. A bellows-based system was used to monitor respiration and provide patient feedback. A randomized controlled clinical trial compared intermittent mode CT fluoroscopy-guided biopsies of the lung or upper abdomen performed with (n = 56) and without (n = 57) the bellows system. Inclusion criteria for 113 patients were lesions 6 cm or smaller in maximum dimension that were not affixed to the chest or abdominal wall. Primary outcome measurements were CT fluoroscopy exposure time and patient dose. Wilcoxon rank sum, chi(2), and Fisher exact tests were used for statistical analysis. RESULTS: Median CT fluoroscopy exposure time was 12.6 seconds (range, 2.4-44.4 seconds) for the bellows group and 18.0 seconds (range, 6.0-118.0 seconds) for the nonbellows group (P = .004). Patient dose was decreased in the bellows group (median dose, 29.5 mGy; range, 4.7-135.8 mGy) versus the nonbellows group (median, 41.3 mGy; range, 11.8-155.9 mGy) (P = .01). Lesions were accessed successfully with one needle puncture attempt in 43 of 56 patients (77%) in the bellows group and 30 of 57 patients (53%) in the nonbellows group (P = .007). Pneumothorax developed in 11 of 50 patients (22%) in the bellows group who underwent lung biopsy compared with 16 of 50 (32%) patients in the nonbellows group. CONCLUSION: A breath-hold monitoring and feedback system allows depiction of mobile target lesions throughout CT fluoroscopy-guided biopsy of the lung and upper abdomen.     

Radical treatment of Hodgkin disease with radiation therapy: results of a 15-year clinical trial. The 1985 Erskine lecture

In 1970, the University of Minnesota Hospitals instituted a policy for treatment of patients with stage I, II, and IIIA Hodgkin disease that required complete staging including laparotomy and extended field or total nodal radiation. Evaluation of the results of this policy in 1974 led to modifications of treatment based on analysis of disease recurrences. Since 1974, patients with large mediastinal masses or hilar disease have been treated with whole-lung or half-lung radiation. In addition, patients with stage IIIA disease with positive spleens were treated with liver irradiation. Sixty-five patients with Hodgkin disease treated with extended or total nodal fields and 126 patients treated with the radical radiation approach are evaluated. The use of this treatment modification has changed the prognostic factors and produced an improvement in recurrence-free survival that is statistically significant. The authors suggest that radical radiation therapy is the treatment of choice in patients with stage IA, IIA, or IIIA Hodgkin disease.     

Definitive proton beam radiation therapy for inoperable gastric cancer: a report of two cases.

Proton beam radiation therapy using 250 MeV protons was carried out on two patients with early gastric cancer (T1, N0, M0). One patient was an 85-year-old man with early gastric cancer of type IIa + IIc. The other one was a 70 year old man with early gastric cancer of type IIc. In both cases histological examination of biopsy specimens showed differentiated adenocarcinoma; distant metastasis was not found by other examinations. Both patients were considered inoperable due to their poor cardiac and/or respiratory functions. Therefore, it was decided to treat them by definitive proton irradiation, delivering total doses of 86 Gy and 83 Gy, respectively. In both patients, skin erythema that did not require any special treatment was found in the irradiation field. Hematobiological examinations did not show any abnormality. Although endoscopic examination at two years after irradiation in the former case and at seven months in the latter case showed persistent gastric ulcer at the site of the cancerous lesions, cancer cells were not found histologically. Therefore, we concluded that proton irradiation therapy was useful for inoperable early gastric cancers.