Hypofractionated External Beam Radiotherapy Research Articles

Patients with recurrent glioblastoma multiforme

SummaryAim: The objective of this study was to assess the feasibility, dosimetry, tolerability and efficacy of systemically administrated p-[131I] - iodo-L-phenylalanine (131IPA) combined with hypo-fractionated external beam radiation therapy (EBRT) in patients with recurrent glioblastoma multiforme (GBM). Patients, methods: Five patients (2 women, 3 men, aged 27-69) with recurrent GBM and exhaustion of regular therapy options were included. All had a positive O-(2-[18F]Fluoroethyl)- L-tyrosine positron emission tomography (FET-PET) and pretherapeutic dosimetry was performed. Tumour targeting was verified by 131IPA-SPECT up to six days after radiotracer administration. After 131IPA therapy, patients were treated with hypo-fractionated EBRT in six fractions of 5 Gy (n = 4) or in eleven fractions of 2 Gy in one case. Results: Based on the individual dosimetry, the patients received a single intravenous administration of 2 to 7 GBq of 131IPA, resulting in radiation absorbed doses to the blood of 0.80–1.47 Gy. The treatment was well tolerated; only minor complaints of nausea and vomiting that responded to ondansetron and pantoprazol were noticed in the first two patients. After preventive medication, the last three patients had no complaints during therapy. In none of the patients a decrease of leukocyte or thrombocyte counts below the baseline level or the lower normal limit was observed. Tumour doses from 131IPA were low (≤ 1 Gy) and all patients died three to eight (median 5.5) months after therapy. Conclusion: In this initial experience, treatment of GBM with 131IPA in combination with EBRT was demonstrated to be safe and well tolerated, but less effective than suggested by the animal studies.

Hypofractionated external-beam radiation therapy (HEBRT) versus conventional external-beam radiation (CEBRT) in patients with localized prostate cancer: a systematic review and meta-analysis

BackgroundThe purpose of this work was to conduct a systematic review and meta-analysis of all randomized controlled trials comparing the efficacy and side effect profile of hypofractionated versus conventional external-beam radiation therapy for prostate cancer.MethodsSeveral databases were searched, including Medline, EmBase, LiLACS, and Central. The endpoints were freedom from biochemical failure and side effects. We performed a meta-analysis of the published data. The results are expressed as the hazard ratio (HR) or risk ratio (RR), with the corresponding 95% confidence interval (CI).ResultsThe final analysis included nine trials comprising 2702 patients. Freedom from biochemical failure was reported in only three studies and was similar in patients who received hypofractionated or conventional radiotherapy (fixed effect, HR 1.03, 95% CI 0.88–1.20; P = 0.75), with heterogeneity [χ2 = 15.32, df = 2 (P = 0.0005); I2 = 87%]. The incidence of acute adverse gastrointestinal events was higher in the hypofractionated group (fixed effect, RR 2.02, 95% CI 1.45–2.81; P < 0.0001). We also found moderate heterogeneity on this analysis [χ2 = 7.47, df = 5 (P = 0.19); I2 = 33%]. Acute genitourinary toxicity was similar among the groups (fixed effect, RR 1.19, 95% CI 0.95–1.49; P = 0.13), with moderate heterogeneity [χ2 = 5.83, df = 4 (P = 0.21); I2 = 31%]. The incidence of all late adverse events was the same in both groups (fixed effect, gastrointestinal toxicity, RR 1.17, 95% CI 0.79–1.72, P = 0.44; and acute genitourinary toxicity, RR 1.16, 95% CI 0.80–1.68, P = 0.44).ConclusionHypofractionated radiotherapy in localized prostate cancer was not superior to conventional radiotherapy and showed higher acute gastrointestinal toxicity in this meta-analysis. Because the number of published studies is still small, future assessments should be conducted to clarify better the true role of hypofractionated radiotherapy in patients with prostate cancer.

Five Year Outcome of 145 Patients With Ductal Carcinoma In Situ (DCIS) After Accelerated Breast Radiotherapy

Accelerated whole-breast radiotherapy (RT) with tumor bed boost in the treatment of early invasive breast cancer has demonstrated equivalent local control and cosmesis when compared with standard RT. Its efficacy in the treatment of ductal carcinoma in situ (DCIS) remains unknown. Patients treated for DCIS with lumpectomy and negative margins were eligible for 2 consecutive hypofractionated whole-breast RT clinical trials. The first trial (New York University [NYU] 01-51) prescribed to the whole breast 42 Gy (2.8 Gy in 15 fractions) and the second trial (NYU 05-181) 40.5 Gy (2.7 Gy in 15 fractions) with an additional daily boost of 0.5 Gy to the surgical cavity. Between 2002 and 2009, 145 DCIS patients accrued, 59 to the first protocol and 86 to the second trial. Median age was 56 years and 65% were postmenopausal at the time of treatment. Based on optimal sparing of normal tissue, 79% of the patients were planned and treated prone and 21% supine. At 5 years' median follow-up (60 months; range 2.6-105.5 months), 6 patients (4.1%) experienced an ipsilateral breast recurrence in all cases of DCIS histology. In 3/6 patients, recurrence occurred at the original site of DCIS and in the remaining 3 cases outside the original tumor bed. New contralateral breast cancers arose in 3 cases (1 DCIS and 2 invasive carcinomas). Cosmetic self-assessment at least 2 years after treatment is available in 125 patients: 91% reported good-to-excellent and 9% reported fair-to-poor outcomes. With a median follow-up of 5 years, the ipsilateral local recurrence rate is 4.1%, comparable to that reported from the NSABP (National Surgical Adjuvant Breast and Bowel Project) trials that employed 50 Gy in 25 fractions of radiotherapy for DCIS. There were no invasive recurrences. These results provide preliminary evidence that accelerated hypofractionated external beam radiotherapy is a viable option for DCIS.

Treating intermediate-risk prostate cancer with hypofractionated external beam radiotherapy alone

PurposeIntermediate-risk prostate cancer has been treated in many ways; the most effective treatment is uncertain. Hypofractionated external beam radiotherapy (HyRT) is a short and convenient alternative treatment. We report our results of HyRT in intermediate-risk patients. Material and methodsEighty two patients with intermediate-risk prostate cancer were treated with 3-dimensional conformal HyRT plans to the dose of 66Gy/22 fractions prescribed at the isocenter without hormones. Intermediate-risk was defined as clinical stage T2b–T2c, or pre-treatment PSA between 10 and 20ng/mL, or Gleason Score equal 7. The planning target volume consisted of the prostate plus a uniform 7mm margin. Toxicity was prospectively graded by the Common Terminology Criteria version3. Biochemical relapse was defined as post-radiotherapy nadir PSA+2ng/mL. ResultsWith a median follow-up of 51months, 5-year actuarial biochemical recurrence free survival is 95.4%. At the last follow-up visit, grade ⩾2 late gastro-intestinal and genito-urinary toxicity rates were 2% and 7%, respectively. No patient ever developed grade 4 or 5 toxicity. ConclusionHyRT to a dose of 66Gy in 22 fractions as a single treatment modality is convenient for patients and for the health care system and appears to provide similar results to other treatment choices.

Single fraction high-dose-rate brachytherapy and hypofractionated external beam radiation therapy in the treatment of intermediate-risk prostate cancer: Long-term results.

83 Background: We present the long-term results of a cohort of patients with intermediate-risk prostate cancer (PC) treated with single fraction high-dose-rate brachytherapy (HDRB) combined with hypofractionated external beam radiation therapy (HRT). Methods: Patients with intermediate-risk PC were treated exclusively with HDRB and HRT. HDRB delivered a dose of 10 Gy to the prostate gland and HRT consisted of 50 Gy delivered in 20 daily fractions. The planning target volume was the prostate gland with a 1 cm margin all around. The first 121 consecutive patients with a minimum of 2 years post-treatment follow-up were assessed for acute and chronic toxicity and disease control. Results: The median follow-up was 62.8 months. No acute grade III or higher toxicities were seen. Grade II late GI toxicity was seen in 9 patients (7.4%) and grade III in 2 (1.6%). Grade 3 GU toxicity was seen in 2 patients (1.6%), both with urinary obstructive symptoms requiring catheterization. A repeat biopsy was offered to the first 58 consecutively treated patients, and 44 patients agreed with the procedure. A negative biopsy was found in 40 patients (91%). The biochemical relapse-free survival rate at 5 and 8 years were 90.7% and 81.4%, with 13 patients presenting biochemical failure. Among them, nine were diagnosed with distant metastasis. Prostate cancer-specific and overall survival rates at 8 years were 100% and 95.5%, respectively. Conclusions: Our program of HDRB and HRT is well tolerated, with acceptable toxicity rates. Furthermore, results from re-biopsies revealed an elevated rate of local control. These results are encouraging and confirm that the use of conformal RT techniques, adapted to specific biological features, have the potential to improve the therapeutic ratio in intermediate risk PC patients. No significant financial relationships to disclose.

Intermediate Risk Prostate Cancer Treated with Hypofractionated External Beam Radiotherapy without Androgen Deprivation: Preliminary Results and Toxicity Analysis

To report late gastrointestinal (GI) and genitourinary (GU) toxicity rates and biochemical control using hypofractionated external beam radiotherapy (HEBRT) without androgen deprivation for intermediate risk prostate cancer (PC) patients.

Health-Related Quality of Life After Single-Fraction High-Dose-Rate Brachytherapy and Hypofractionated External Beam Radiotherapy for Prostate Cancer

To investigate the change in health-related quality of life for men after high-dose-rate brachytherapy and external beam radiotherapy for prostate cancer and the factors associated with this change. Eligible patients had clinically localized intermediate-risk prostate cancer. The patients received high-dose-rate brachytherapy as a single 15-Gy implant, followed by external beam radiotherapy to 37.5 Gy in 15 fractions. The patients were monitored prospectively for toxicity (Common Terminology Criteria for Adverse Events, version 3.0) and health-related quality of life (Expanded Prostate Cancer Index Composite [EPIC]). The proportion of patients developing a clinically significant difference in the EPIC domain score (minimally important difference of >0.5 standard deviation) was determined and correlated with the baseline clinical and dosimetric factors. The study accrued 125 patients, with a median follow-up of 24 months. By 24 months, 23% had Grade 2 urinary toxicity and only 5% had Grade 2 bowel toxicity, with no Grade 3 toxicity. The proportion of patients reporting a significant decrease in EPIC urinary, bowel, sexual, and hormonal domain scores was 53%, 51%, 45%, and 40% at 12 months and 57%, 65%, 51%, and 30% at 24 months, respectively. The proportion with a >1 standard deviation decrease in the EPIC urinary, bowel, sexual, and hormonal domain scores was 38%, 36%, 24%, and 20% at 12 months and 46%, 48%, 19%, and 8% at 24 months, respectively. On multivariate analysis, the dose to 10% of the urethra was associated with a decreasing EPIC urinary domain score (p = .0089) and, less strongly (p = .0312) with a decreasing hormonal domain score. No association was found between the prostate volume, bladder dose, or high-dose volume and urinary health-related quality of life. A high baseline International Index of Erectile Function score was associated (p = .0019) with a decreasing sexual domain score. The optimal maximal dose to 10% of the urethra cutpoint for urinary health-related quality of life was 120% of the prescription dose. EPIC was a more sensitive tool for detecting the effects on function and bother than were the generic toxicity scales. The urethral dose had the strongest association with a deteriorating urinary quality of life.

Preliminary Results of Electron Intraoperative Therapy Boost and Hypofractionated External Beam Radiotherapy After Breast-Conserving Surgery in Premenopausal Women

To report the acute and preliminary data on late toxicity of a pilot study of boost with electron intraoperative therapy followed by hypofractionated external beam radiotherapy (HEBRT) of the whole breast. Between June 2004 and March 2007, 211 women with a diagnosis of early-stage breast cancer were treated with breast-conserving surgery. During surgery, an electron intraoperative therapy boost of 12 Gy was administered to the tumor bed. Adjuvant local treatment was completed with HEBRT, consisting of a course of 13 daily fractions of 2.85 Gy to the whole breast to a total dose of 37.05 Gy. Acute toxicity of the breast was evaluated at the end of HEBRT and at 1 month of follow-up. Late toxicity was recorded at 6 and 12 months of follow-up. We report the data from 204 patients. The maximal acute skin toxicity was observed at the end of HEBRT (182 patients evaluable) with 7 (3.8%) Grade 3, 52 (28.6%) Grade 2, 123 (67.6%) Grade 1, and no Grade 0 or Grade 4 cases. A total of 108 patients were evaluated for late toxicity. The recorded late skin toxicity was Grade 4 in 1 patient (0.9%), Grade 3 in 1 patient, and Grade 2 or less in 106 patients (98.2%). The results of this study have shown that electron intraoperative therapy followed by HEBRT allows for the delivery of a high dose to the tumor bed and an adequate dose to the whole breast. This treatment is feasible, compliance is high, and the rate of acute toxicity and the preliminary data on chronic toxicity seem acceptable.

Accelerated partial breast irradiation: An advanced form of hypofractionation

Altered fractionation schedules are being increasingly investigated in the treatment of breast cancer. Two such schedules that are frequently compared are hypofractionated external beam radiation therapy (HERT) and accelerated partial breast irradiation (APBI). Though these two modalities are considered separately, APBI is an actually an advanced form of hypofractionation, where acceleration of the treatment is possible due to the smaller volume being irradiated. HERT as well as APBI are investigational at present and are being tested in randomized trials. This article looks at the advantages of APBI as a hypofractionation schedule.

Toxicity after hypofractionated external beam radiotherapy (70 GY at 2.5 GY per fraction) versus standard fractionation radiotherapy (78 GY at 2.0 GY per fraction) for localized prostate cancer

Purpose/Objective: To compare the acute and late toxicity between hypofractionated external beam radiotherapy (HypoFx) delivering 70 Gy in 28 fractions and standard fractionation radiotherapy (StdFx) delivering 78 Gy in 39 fractions.