Hypofractionation In Patients Research Articles

Preliminary results of hypofractionated radiotherapy in breast cancer in Chandigarh, India: single-centre, non-inferiority, open-label, randomised, phase 3 trial

Globally, most of the randomised trials with hypofractionation in patients with breast cancer have used 3-dimensional conformal radiotherapy technique (3D-CRT). As facilities for 3D-CRT technique may not be available in low-resource settings, there is a need to see if hypofractionation is feasible and safe with 2-dimensional (2-D) technique. In this study, we compared a 3-week radiation schedule with a 2-week schedule of hypofractionated radiotherapy in patients with breast cancer with 2-D technique. The current study was an open-label, randomised, phase 3 trial. Patients with breast cancer, stage I-III, post mastectomy or after breast conservative surgery who needed adjuvant locoregional radiotherapy were randomised in the Department of Radiotherapy & Oncology, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, India; to 34Gy in 10 fractions over 2 weeks (2-week arm) or 35Gy in 15 fractions over 3 weeks to the chest wall and 40Gy/15#/3wks to breast and supraclavicular fossa (3-week arm). Boost dose when indicated was 8-10Gy/2-4#/2-4 days in both the arms. Patients were planned on a 2-dimensional (2D) simulator with 2 tangential fields to breast/chest wall and incident supraclavicular fossa field. Acute toxicity was assessed using the Radiation Therapy Oncology Group (RTOG) grading scale. Assessments were carried out weekly during radiotherapy and at 4 weeks after treatment by the physician. Cosmetic outcome was assessed using the Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/RTOG scale. The toxicity rates between the two arms were compared using Fisher's exact tests. The trial was approved by institutional ethics committee and registered with ClinicalTrials.gov, number NCT04075058. This study included 1121 eligible patients from June 2015 to December 2020. Median follow-up was 35 months (6-84 months). Mean age was 48 years (24-75 years). The patient characteristics were comparable between the two arms except for more mastectomies in the 3-week arm and more node-positive patients in the 2-week arm. There were more oestrogen receptor-positive tumors in the 3-week arm. Acute skin toxicities were comparable between the two arms. Grade 2 and 3 skin toxicity was 100 (18%) and 82 (15%); and 16 (3%) and 12 (2%) in the 3-week and 2-week arm (p=0.21), respectively. Cosmetic outcome was assessed as Excellent or Good for 89% of patients in the 3-week arm as compared to 94% in the 2-week arm (p=0.004). The two radiation schedules were comparable in terms of acute skin toxicity. The cosmetic outcome was better with the 2-week schedule. The preliminary findings indicate 2-week radiotherapy schedule with 2-D technique was better than the 3-week schedule in patients with breast cancer. However, disease outcomes and late-term toxicities need to be further checked. This study was funded by Science and Engineering Research Board (SERB), India.

Conventional versus hypofractionated postmastectomy proton radiotherapy in the USA (MC1631): a randomised phase 2 trial

Proton therapy is under investigation in breast cancer as a strategy to reduce radiation exposure to the heart and lungs. So far, studies investigating proton postmastectomy radiotherapy (PMRT) have used conventional fractionation over 25-28 days, but whether hypofractionated proton PMRT is feasible is unclear. We aimed to compare conventional fractionation and hypofractionation in patients with indications for PMRT, including those with immediate breast reconstruction. We did a randomised phase 2 trial (MC1631) at Mayo Clinic in Rochester (MN, USA) and Mayo Clinic in Arizona (Phoenix, AZ, USA) comparing conventional fractionated (50 Gy in 25 fractions of 2 Gy [relative biological effectiveness of 1·1]) and hypofractionated (40·05 Gy in 15 fractions of 2·67 Gy [relative biological effectiveness of 1·1]) proton PMRT. All patients were treated with pencil-beam scanning. Eligibility criteria included age 18 years or older, an Eastern Cooperative Oncology Group performance status of 0-2, and breast cancer resected by mastectomy with or without immediate reconstruction with indications for PMRT. Patients were randomly assigned (1:1) to either conventional fractionation or hypofractionation, with presence of immediate reconstruction (yes vs no) as a stratification factor, using a biased-coin minimisation algorithm. Any patient who received at least one fraction of protocol treatment was evaluable for the primary endpoint and safety analyses. The primary endpoint was 24-month complication rate from the date of first radiotherapy, defined as grade 3 or worse adverse events occurring from 90 days after last radiotherapy or unplanned surgical interventions in patients with immediate reconstruction. The inferiority of hypofractionation would not be ruled out if the upper bound of the one-sided 95% CI for the difference in 24-month complication rate between the two groups was greater than 10%. This trial is registered with ClinicalTrials.gov, NCT02783690, and is closed to accrual. Between June 2, 2016, and Aug 23, 2018, 88 patients were randomly assigned (44 to each group), of whom 82 received protocol treatment (41 in the conventional fractionation group and 41 in the hypofractionation group; median age of 52 years [IQR 44-64], 79 [96%] patients were White, two [2%] were Black or African American, one [1%] was Asian, and 79 [96%] were not of Hispanic ethnicity). As of data cutoff (Jan 30, 2023), the median follow-up was 39·3 months (IQR 37·5-61·2). The median mean heart dose was 0·54 Gy (IQR 0·30-0·72) for the conventional fractionation group and 0·49 Gy (0·25-0·64) for the hypofractionation group. Within 24 months of first radiotherapy, 14 protocol-defined complications occurred in six (15%) patients in the conventional fractionation group and in eight (20%) patients in the hypofractionation group (absolute difference 4·9% [one-sided 95% CI 18·5], p=0·27). The complications in the conventionally fractionated group were contracture (five [12%] of 41 patients]) and fat necrosis (one [2%] patient) requiring surgical intervention. All eight protocol-defined complications in the hypofractionation group were due to infections, three of which were acute infections that required surgical intervention, and five were late infections, four of which required surgical intervention. All 14 complications were in patients with immediate expander or implant-based reconstruction. After a median follow-up of 39·3 months, non-inferiority of the hypofractionation group could not be established. However, given similar tolerability, hypofractionated proton PMRT appears to be worthy of further study in patients with and without immediate reconstruction. The Department of Radiation Oncology, Mayo Clinic, Rochester, MN, the Department of Radiation Oncology, Mayo Clinic, Phoenix, AZ, USA, and the US National Cancer Institute.

Abstract P1-10-03: Ultra-hypofractionated Radiotherapy for Breast Cancer: A Brazilian Single-Institutional Series

Abstract INTRODUCTION Extreme hypofractionation in patients with early-stage breast cancer has been studied in randomized phase III non-inferiority trials. There is scarce data on this strategy in Latin American patients. OBJECTIVES To describe the profile of patients diagnosed with breast cancer treated with radiotherapy with an ultra-hypofractionated regimen (5 fractions of 5.2 Gy, in one week), as well as the dosimetric aspects and acute toxicity related to the treatment. METHOD Retrospective cohort through a Brazilian uni-institutional series, with analysis of pathological, dosimetric, and toxicity variables. RESULTS Between May 2020 and March 2022, 67 patients were included, with a median age at diagnosis of 71 years (41-93). Regarding staging, 25.8% had in situ tumors, 60.6% of patients were IA, and only 3% were stage IIA. Nineteen percent of patients had histological grade 3; 24.6%, had nuclear grade 3. Hormone receptors were positive in 92.1% of patients. The mean ki67 was 19%, and HER2 was negative at 84.5%. All patients underwent conservative surgery, and 5 underwent reconstruction with autologous flaps. Fifty-one patients underwent hormone therapy and only 2 underwent adjuvant chemotherapy. All but two patients were treated with the conformal technique (VMAT was used due to unfavorable anatomy). The mean volume of the irradiated breast was 926 cm3 (ranging from 920 to 932 cm3). Regarding the constraints of the organs at risk, the average V8Gy of the ipsilateral lung was 11.4%, ranging from 0 to 24%. In the heart, the average volumes receiving 1.5Gy and 7Gy were, respectively, 9.2% and 0.7%. No patient had acute toxicity greater than grade 2. The effects on the skin appeared on average 20 days after the end of treatment, with resolution in a maximum of 3 months. The median follow-up time was 10 months (3 - 26). We did not observe any case of local-recurrence, of breast-cancer-related death. CONCLUSION Although our follow-up time is premature, we have found that ultra-hypofractionated radiotherapy was feasible, tolerable, and safe, for patients with early breast cancer. Also, the constraints on the organs at risk were respected. There were no high-grade acute toxicities. Besides convenience, ultra-hypofractionation can improve access to radiotherapy in resource-scarce settings. Citation Format: Leticia Hernandes de Brito, Felipe Cicci Farinha Restini, Maria Thereza Mansur Starling, Gabriela Silva Moreira de Siqueira, Gustavo Nader Marta, Heloisa de Andrade Carvalho, Samir Abdallah Hanna. Ultra-hypofractionated Radiotherapy for Breast Cancer: A Brazilian Single-Institutional Series [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-10-03.

Stereotactic Radiotherapy after Radical Prostatectomy in Patients with Prostate Cancer in the Adjuvant or Salvage Setting: A Systematic Review.

Simple SummaryStereotactic body radiotherapy, a type of high-precision radiotherapy delivering high doses within few treatment sessions has proven to be effective and well tolerated in prostate cancer patients treated with definite radiotherapy. This systematic review summarizes the available data and analyzes whether this modern treatment may routinely be offered to prostate cancer patients after radical prostatectomy.(1) Background: Prostate cancer is the most common cancer in men and can be treated with radical prostatectomy (RPE) or radiotherapy in the primary setting. Stereotactic radiotherapy (SBRT) has proven to be effective and well tolerated in this setting. However, if SBRT is an equally promising treatment option if applied in the adjuvant or salvage setting after RPE remains unknown. (2) Methods: We searched the PubMed and Embase databases with the following full-text queries in August 2021 for any combination of the terms “SBRT”, “prostate”, “adjuvant”, “postoperative”, “salvage”, “stereotactic radiotherapy”, “prostate bed”. There were no limitations regarding publication date or language. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. (3) Results: We identified 11 individual studies that were included in this systematic review. Three publications included patients without prior radiotherapy and the remaining eight patients with prior radiotherapy. In all but two publications the radiation target was the macroscopic recurrence. SBRT was overall well tolerated with acceptable rates of acute and late gastrointestinal or genitourinary toxicity. Quality of life was published for two phase I trials with good results. There was a very heterogeneous reporting on biochemical control after SBRT. (4) Conclusions: At this point, ultra-hypofractionated RT using SBRT to the prostate bed remains experimental and its use should be restricted to clinical trials. Given the biological rationale for extreme hypofractionation in patients with prostate cancer and the acceptable toxicity rates that have been reported, further exploration of this field is warranted.

Disease Control After Hypofractionation Versus Conventional Fractionation for Triple Negative Breast Cancer: Comparative Effectiveness in a Large Observational Cohort

Questions remain about whether moderately hypofractionated whole-breast irradiation is appropriate for patients with triple-negative breast cancer. Using the prospective database of a multicenter, collaborative quality improvement consortium, we identified patients with node-negative, triple-negative breast cancer who received whole-breast irradiation with either moderate hypofractionation or conventional fractionation. Using inverse probability of treatment weighting (IPTW), we compared outcomes using the Kaplan-Meier product-limit estimation method with Cox regression models estimating the hazard ratio for time-to-event endpoints between groups. The sample included 538 patients treated at 18 centers in 1 state in the United States, of whom 307 received conventionally fractionated whole-breast irradiation and 231 received moderately hypofractionated whole-breast irradiation. The median follow-up time was 5.0 years (95% confidence interval [CI], 4.77-5.15 years). The 5-year IPTW estimates for freedom from local recurrence were 93.6% (95% CI, 87.8%-96.7%) in the moderate hypofractionation group and 94.4% (95% CI, 90.3%-96.8%) in the conventional fractionation group. The hazard ratio was 1.05 (95% CI, 0.51-2.17; P=.89). The 5-year IPTW estimates for recurrence-free survival were 87.8% (95% CI, 81.0%-92.4%) in the moderate hypofractionation group and 88.4% (95% CI 83.2%-92.1%) in the conventional fractionation group. The hazard ratio was 1.02 (95% CI, 0.62-1.67; P=.95). The 5-year IPTW estimates for overall survival were 96.6% (95% CI, 92.0%-98.5%) in the moderate hypofractionation group and 93.4% (95% CI, 88.7%-96.1%) in the conventional fractionation group. The hazard ratio was 0.65 (95% CI, 0.30-1.42; P=.28). Analysis of outcomes in this large observational cohort of patients with triple-negative, node-negative breast cancer treated with whole-breast irradiation revealed no differences by dose fractionation. This adds evidence to support the use of moderate hypofractionation in patients with triple-negative disease.

Radiation dose to the heart with hypofractionation in patients with left breast cancer

Abstract Introduction In this study we compared radiation dose received by organs at risk (OARs) after breast conservation surgery(BCS) and mastectomy in patients with left breast cancer. Materials and methods Total 30 patients, 15 each of BCS and mastectomy were included in this study. Planning Computerised Tomography (CT) was done for each patient. Chest wall, whole breast, heart, lungs, LAD, proximal and distal LAD, and contra lateral breast was contoured for each patient. Radiotherapy plans were made by standard tangent field. Dose prescribed was 40Gy/16#/3 weeks. Mean heart dose, LAD, proximal and distal LAD, mean and V5 of right lung, and mean, V5, V10 and V20 of left lung, mean dose and V2 of contra lateral breast were calculated for each patient and compared between BCS and mastectomy patients using student’s T test. Results Mean doses to the heart, LAD, proximal LAD and distal LAD were 3.364Gy, 16.06Gy, 2.7Gy, 27.5Gy; and 4.219Gy, 14.653Gy, 4.306Gy, 24.6Gy, respectively for mastectomy and BCS patients. Left lung mean dose, V5, V10 and V20 were 5.96Gy, 16%, 14%, 12.4%; and 7.69Gy, 21%, 18% and 16% in mastectomy and BCS patients, respectively. There was no statistical significant difference in the doses to the heart and left lung between mastectomy and BCS. Mean dose to the right lung was significantly less in mastectomy as compared to BCS, 0.29Gy vs. 0.51Gy, respectively (p = 0.007). Mean dose to the opposite breast was significantly lower in patients with mastectomy than BCS (0.54Gy Vs 0.37Gy, p = 0.007). The dose to the distal LAD was significantly higher than proximal LAD both in BCS (24.6Gy Vs 4.3Gy, p = <0.0001) and mastectomy (27.5Gy Vs 2.7Gy, p = <0.0001) patients. Conclusion There was no difference in doses received by heart and left lung between BCS and mastectomy patients. Mean doses to the right lung and breast were significantly less in mastectomy patients.

Late-term effects of hypofractionated chest wall and regional nodal radiotherapy with two-dimensional technique in patients with breast cancer

PurposeHypofractionated radiotherapy (RT) is becoming a new standard in postoperative treatment of patients with early stage breast cancer after breast conservation surgery. However, data on hypofractionation in patients with advanced stage disease who undergo mastectomy followed by local and regional nodal irradiation (RNI) is lacking. In this retrospective study, we report late-term effects of 3 weeks post-mastectomy hypofractionated local and RNI with two-dimensional (2D) technique in patients with stage II and III breast cancer. MethodsBetween January 1990 and December 2007, 1,770 women with breast cancer who were given radical treatment with mastectomy, systemic therapy and RT at least 10 years ago were included. RT dose was 35 Gy/15 fractions/3 weeks to chest wall by two tangential fields and 40 Gy in same fractions to supraclavicular fossa (SCF) and internal mammary nodes (IMNs). SCF and IMNs dose was prescribed at dmax and 3 cm depth, respectively. Chemotherapy and hormonal therapy was given in 64% and 74% patients, respectively. Late-term toxicities were assessed with the Radiation Therapy Oncology Group (RTOG) scores and LENT-SOMA scales (the Late Effects Normal Tissue Task Force-Subjective, Objective, Management, Analytic scales). ResultsMean age was 48 years (range, 19 to 75 years). Median follow-up was 12 years (range, 10 to 27 years). Moderate/marked arm/shoulder pain was reported by 254 (14.3%) patients. Moderate/marked shoulder stiffness was reported by 219 (12.3%) patients. Moderate/marked arm edema was seen in 131 (7.4%) patients. Brachial plexopathy was not seen in any patient. Rib fractures were noted in 6 (0.3%) patients. Late cardiac and lung toxicity was seen in 29 (1.6%) and 23 (1.3%) patients, respectively. Second malignancy developed in 105 (5.9%) patients.ConclusionRNI with 40 Gy/15 fractions/3 weeks hypofractionation with 2D technique seems safe and comparable to historical data of conventional fractionation (ClinicalTrial.gov Registration No. NCT04175821).

Quality of life after breast-conserving therapy and adjuvant radiotherapy for non-low-risk ductal carcinoma in situ (BIG 3-07/TROG 07.01): 2-year results of a randomised, controlled, phase 3 trial

BIG 3-07/TROG 07.01 is an international, multicentre, randomised, controlled, phase 3 trial evaluating tumour bed boost and hypofractionation in patients with non-low-risk ductal carcinoma in situ following breast-conserving surgery and whole breast radiotherapy. Here, we report the effects of diagnosis and treatment on health-related quality of life (HRQOL) at 2 years. The BIG 3-07/TROG 07.01 trial is ongoing at 118 hospitals in 11 countries. Women aged 18 years or older with completely excised non-low-risk ductal carcinoma in situ were randomly assigned, by use of a minimisation algorithm, to tumour bed boost or no tumour bed boost, following conventional whole breast radiotherapy or hypofractionated whole breast radiotherapy using one of three randomisation categories. Category A was a 4-arm randomisation of tumour bed boost versus no boost following conventional whole breast radiotherapy (50 Gy in 25 fractions over 5 weeks) versus hypofractionated whole breast radiotherapy (42·5 Gy in 16 fractions over 3·5 weeks). Category B was a 2-arm randomisation between tumour bed boost versus no boost following conventional whole breast radiotherapy, and category C was a 2-arm randomisation between tumour bed boost versus no boost following hypofractionated whole breast radiotherapy. Stratification factors were age at diagnosis, planned endocrine therapy, and treating centre. The primary endpoint, time to local recurrence, will be reported when participants have completed 5 years of follow-up. The HRQOL statistical analysis plan prespecified eight aspects of HRQOL, assessed by four questionnaires at baseline, end of treatment, and at 6, 12, and 24 months after radiotherapy: fatigue and physical functioning (EORTC QLQ-C30); cosmetic status, breast-specific symptoms, arm and shoulder functional status (Breast Cancer Treatment Outcome Scale); body image and sexuality (Body Image Scale); and perceived risk of invasive breast cancer (Cancer Worry Scale and a study-specific question). For each of these measures, tumour bed boost was compared with no boost, and conventional whole breast radiotherapy compared with hypofractionated whole breast radiotherapy, by use of generalised estimating equation models. Analyses were by intention to treat, with Hochberg adjustment for multiple testing. This trial is registered with ClinicalTrials.gov, NCT00470236. Between June 1, 2007, and Aug 14, 2013, 1208 women were enrolled and randomly assigned to receive no tumour bed boost (n=605) or tumour bed boost (n=603). 396 of 1208 women were assigned to category A: conventional whole breast radiotherapy with tumour bed boost (n=100) or no boost (n=98), or to hypofractionated whole breast radiotherapy with tumour bed boost (n=98) or no boost (n=100). 447 were assigned to category B: conventional whole breast radiotherapy with tumour bed boost (n=223) or no boost (n=224). 365 were assigned to category C: hypofractionated whole breast radiotherapy with tumour bed boost (n=182) or no boost (n=183). All patients were followed up at 2 years for the HRQOL analysis. 1098 (91%) of 1208 patients received their allocated treatment, and most completed their scheduled HRQOL assessments (1147 [95%] of 1208 at baseline; 988 [87%] of 1141 at 2 years). Cosmetic status was worse with tumour bed boost than with no boost across all timepoints (difference 0·10 [95% CI 0·05-0·15], global p=0·00014, Hochberg-adjusted p=0·0016); at the end of treatment, the estimated difference between tumour bed boost and no boost was 0·13 (95% CI 0·06-0·20; p=0·00021), persisting at 24 months (0·13 [0·06-0·20]; p=0·00021). Arm and shoulder function was also adversely affected by tumour bed boost across all timepoints (0·08 [95% CI 0·03-0·13], global p=0·0033, Hochberg adjusted p=0·045); the difference between tumour bed boost and no boost at the end of treatment was 0·08 (0·01 to 0·15, p=0·021), and did not persist at 24 months (0·04 [-0·03 to 0·11], p=0·29). None of the other six prespecified aspects of HRQOL differed significantly after adjustment for multiple testing. Conventional whole breast radiotherapy was associated with worse body image than hypofractionated whole breast radiotherapy at the end of treatment (difference -1·10 [95% CI -1·79 to -0·42], p=0·0016). No significant differences were reported in the other PROs between conventional whole breast radiotherapy compared with hypofractionated whole breast radiotherapy. Tumour bed boost was associated with persistent adverse effects on cosmetic status and arm and shoulder functional status, which might inform shared decision making while local recurrence analysis is pending. National Health and Medical Research Council, Susan G Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society.

Abstract IA31: Radiation therapy in lung cancer: Recent trends and future directions

Abstract Radiation techniques for lung cancer have evolved substantially over the past decade. While previously many patients were treated with 3D conformal therapy, with large uniform margins placed to estimate respiratory motion in the “average” tumor, patients are now simulated with sophisticated, real-time monitoring of internal motion such that treatment volumes can be individualized to maximize normal tissue sparing through image-guided radiation therapy (IGRT). In addition, many patients are now treated with intensity-modulated radiation therapy (IMRT), which has served to drastically improve conformality in select cases and increase the proportion of patients in which high doses are achievable. Concurrent with these advances, proton beam therapy (PBT) has been implemented in a limited number of centers, with the hope of utilizing the dosimetric distribution advantage of the Bragg Peak to further reduce toxicity. The role of PBT in both early-stage and locally advanced non-small cell lung cancer continues to be defined, as results from a phase II multicenter randomized trial predominantly in patients with stage II-III disease did not demonstrate superiority with PBT and concurrent chemotherapy when compared to similar regimens with IMRT. Finally, there have been much data produced with regard to dosing regimens. In early-stage disease, there has been increased implementation of stereotactic ablative body radiation (SABR), with prospective data emerging for both peripheral and central lesions. In the locally advanced setting, results from RTOG 0617 demonstrated no difference when comparing 60 Gy vs. 74 Gy in the setting of chemoradiation. There has also been a trend towards hypofractionation for patients who are unable to tolerate concurrent chemoradiation or those with oligometastatic disease, yet the benefit of hypofractionated radiation sequentially vs. combined modality treatment will need to be further assessed in prospective randomized trials, particularly in the era of immunotherapy. Citation Format: Daniel R. Gomez. Radiation therapy in lung cancer: Recent trends and future directions [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr IA31.

Moderate Hypofractionation in Patients with Low-risk Prostate Cancer: Long-term Outcomes.

To evaluate outcomes in patients with low-risk prostate cancer treated with hypofractionated radiotherapy (HyRT). Between April 2004 and December 2015, 175 patients with low-risk prostate cancer were treated with HyRT 60 Gy in 20 fractions with or without image guidance and reduction of margin from clinical target volume to planning target volume. The median follow-up was 66 months. The 8-year overall survival for the whole patient cohort was 88.9%. The 8-year biochemical no evidence of disease was higher in patients treated with image-guided HyRT (98.8% vs. 88%, p=0.023). During treatment, patients treated with image-guided HyRT presented a lower rate of grade 1-2 gastrointestinal toxicity (25.3% vs. 42.2%, p=0.001). At the last follow-up, the grade 1 Gastro-intestinal toxicity rate was 4.0% and the grade 1-2 genito-urinary toxicity rate was 25.1%. Our study demonstrated the efficacy of the schedule used with a low rate of acute and late toxicities. Therefore, reduction of margins with image-guided HyRT is safe.

Hypofractionated radiation therapy for prostate cancer: The McGill University Health Center experience

PurposeIn 2002, at the McGill University Health Centre, we began a program of hypofractionated radiotherapy for patients with low risk prostate cancer as an alternative to conventionally fractionated radiotherapy. Material and methodsOur initial hypofractionation regimen was 66Gy given in 22 fractions, prescribed to the isocenter, delivered with 3D-conformal radiotherapy plan. The clinical target volume was the prostate gland and the planning target volume consisted of the clinical target volume plus a 7-mm margin in all directions. Hormonal therapy was not given to any patient. ResultsThe long-term results for this group of patients confirmed the feasibility, good tolerance and excellent disease control of the regimen with the extra-benefit of being convenient to both patients and the health system by shortening treatment duration. The outcomes of this approach stimulated us to use hypofractionation in patients with intermediate-risk. Analysis of 100 intermediate-risk patients receiving our hypofractionated radiotherapy regimen (no hormones) shows, at median follow-up of 75 months, 8-year biochemical recurrence free and cancer specific survival rates of 90% and 95%, respectively, with acceptable toxicity. DiscussionOur technique changed from 3D to intensity modulated radiotherapy with the dose adjusted to 60Gy in 20 fractions. Lastly, we have expanded the program to high-risk patients where IMRT treatments are given to the pelvic nodes (44Gy in 20 fractions) with a simultaneous integrated boost delivery to the prostate (60Gy in the same 20 fractions). Our long-term results have shown that moderate hypofractionated radiotherapy for prostate cancer is safe and provides good tumor control comparable to high-dose conventionally fractionated radiotherapy. This hypofractionated regimen has been routinely used in our institution.

Napromienianie dwa razy dziennie podwyższoną dawką frakcyjną chorych z przerzutami nowotworów złośliwych do mózgu. Wyniki końcowe prospektywnego badania klinicznego w nierandomizowanej grupie chorych

Aim To evaluate the morbidity and effectivness of twice a day hypofractionation in patients with brain metastases. Material / methods Between 1992 and 2000, 116 patients with brain metastases have been treated with whole brain radiotherapy alone and only in 33 patients radiotherapy was applied as adjuvant treatment after surgery. Radiotherapy was given in two of 3 Gy fractions daily with minimum 6 hours intervals between fractions to total dose of 39 Gy. Mean age of treated patients was 55 years. All patients were in general performance status evaluated according to the Karnofsky Performance Scale of at least 50. Results Early tolerance of treatment was acceptable. Of 116 patients only 20 patients were treated with supportive treatment (anti-oedema drugs). Improvement of the neurological status was obtained in 26 patients (22%). The one-year overall survival was 21%. The one–year survival without clinical progression of disease was observed in 10% of all treated patients. Patients with solitary brain metastases treated with surgery and radiotherapy showed the best results. Conclusions Our results showed that twice a day hypo-fractionation radiotherapy for patients with brain metastases is well tolerated and may provides benefit.

Hypofractionation in glioblastoma multiforme

Purpose: To compare conventional fractionation with hypofractionation in patients with a glioblastoma multiforme. Endpoints of the analysis are overall survival and palliative effect. Materials and methods: From 1988 to 1998, 155 patients with pathologically confirmed glioblastoma multiforme were prospectively analysed. Patients without irradiation and patients receiving an interstitial boost were excluded from this analysis. Three different radiation schemes were used in subsequent periods; 33×2, 8×5 and 4×7 Gy. In the last 5 years a scheme of 4×7 Gy conformal irradiation was given to poor prognosis patients. The more favourable group received the conventionally fractionated scheme up to 66 Gy. Results: Median survival was 7, 5.6 and 6.6 months for the 33×2, 8×5 and 4×7 Gy, respectively. In general, patients in the hypofractionation group had far worse prognostic factors compared with patients treated with the conventional scheme. The period of neurological improvement or stabilisation was similar between the 4×7 and 33×2 Gy group. Conclusion: An extreme hypofractionation scheme of 4×7 Gy conformal irradiation in poor prognostic glioblastoma patients is well tolerated, convenient for the patient and provides equal palliation without negative effects on survival compared with conventional fractionation.