Altered Fractionation in Radiotherapy

1998 ◽  
Vol 84 (2) ◽  
pp. 155-159 ◽  
Author(s):  
Riccardo Valdagni
Keyword(s):  
Treatment Time ◽  
Clinical Results ◽  
Therapeutic Benefit ◽  
Phase Iii ◽  
Overall Treatment Time ◽  
Conventional Fractionation ◽  
Normal Tissues ◽  
Normal Tissue Damage ◽  
Altered Fractionation ◽  
Cell Repopulation

Differences between late-responding (slowly proliferating) normal tissues and early-responding (rapidly proliferating) normal tissues and tumor cells and the event of tumor cell repopulation occurring during treatment have essentially led to the development of altered fractionation schemes. Altered fractionation regimens mainly refer to schedules utilising two or more (small dose) fractions per day for part of or for the entire treatment course. It must be underlined that a true standard or conventional fractionation regimen does not exist: no schedule is universally recognised as the standard of reference to be compared with. However, continental European and U.S. conventional regimens are the considered control arm with which the new experimental regimens have to be compared. For this reason they are generally recognised as the standards. The basic rationale for hyperfractionated or accelerated regimens respectively lies in the possibility (a) to deliver higher total doses reducing late-responding normal tissue damage, (b) to deliver total doses in a reduced overall treatment time to defeat tumor clonogen repopulation. Multiple fractions per day should not be delivered with interfraction intervals smaller than 6 hours. Clinical results of phase I-II and limited but convincing phase III randomised trials suggest that a therapeutic benefit can be achieved with new altered regimens.

scholarly journals PPARs in Irradiation-Induced Gastrointestinal Toxicity

PPAR Research ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Christine Linard ◽  
Maâmar Souidi
Keyword(s):  
Normal Tissue ◽  
Treatment Time ◽  
Therapeutic Benefit ◽  
Gastrointestinal Toxicity ◽  
Overall Treatment Time ◽  
Inflammatory Reactions ◽  
Normal Tissues ◽  
Inflammatory Processes ◽  
Patients Experience ◽  
Abdominal Irradiation

The use of radiation therapy to treat cancer inevitably involves exposure of normal tissues. Although the benefits of this treatment are well established, many patients experience distressing complications due to injury to normal tissue. These side effects are related to inflammatory processes, and they decrease therapeutic benefit by increasing the overall treatment time. Emerging evidence indicates that PPARs and their ligands are important in the modulation of immune and inflammatory reactions. This paper discusses the effects of abdominal irradiation on PPARs, their role and functions in irradiation toxicity, and the possibility of using their ligands for radioprotection.

The PACE trial: International randomised study of laparoscopic prostatectomy vs. stereotactic body radiotherapy (SBRT) and standard radiotherapy vs. SBRT for early stage organ-confined prostate cancer.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. TPS153-TPS153 ◽  
Author(s):  
Kirsty Morrison ◽  
Alison Tree ◽  
Vincent Khoo ◽  
Nicholas John Van As ◽  
Keyword(s):  
Prostate Cancer ◽  
Stereotactic Body Radiotherapy ◽  
Treatment Time ◽  
Early Stage ◽  
Treatment Options ◽  
Therapeutic Benefit ◽  
Phase Iii ◽  
Overall Treatment Time ◽  
Multicentre Phase ◽  
Randomised Study

TPS153 Background: The development of Stereotactic Body Radiotherapy (SBRT) has provided a further treatment option for early stage prostate cancer. In addition to the benefits of an overall treatment time reduction, profound hypofractionation could result in therapeutic gain given the radiobiology of prostate cancer. Evidence suggests SBRT to be safe and effective; however randomised data is lacking comparing outcomes with standard treatment options. Aim: To assess whether SBRT offers therapeutic benefit in comparison to prostatectomy or standard radiotherapy. Methods: The PACE trial is an international multicentre phase III trial, comprising two parallel randomisation processes. Within PACE A, potential surgical candidates are randomised between radical prostatectomy and SBRT (36.25 Gy in 5 fractions). In PACE B, randomisation is between standard radiotherapy (78Gy in 39 fractions or 62Gy in 20 fractions) and SBRT (36.35Gy in 5 fractions). SBRT can be delivered using Cyberknife or gantry based techniques. Patients with low or intermediate risk prostate cancer are eligible for the trial, and are treated without the use androgen deprivation therapy. Follow up is for a period of 10 years. The aim is to recruit 234 patients to PACE A (117 in each arm) and 858 patients to PACE B (429 patients in each arm). Primary Objectives: PACE A: To determine whether there is improved quality of life after SBRT compared with surgery at 2 years post treatment, using EPIC score to measure urinary incontinence and bowel bother. PACE B: to determine whether SBRT is non-inferior to surgery in terms of freedom from biochemical/clinical failure at 5 years from randomisation. Progress: PACE A has been slower to recruit than anticipated due to the difficulties of a surgery versus radiotherapy randomisation. However, it is expected to reach target accrual, having recruited 57 patients from 3 centres. In contrast, PACE B is recruiting exceptionally well, open in 40 centres, and as of October 2017 recruited 762 patients. Accrual target is expected to be reached by the end of 2017. Clinical trial information: NCT01584258.

Altered Fractionation Schedules in Radiotherapy of Head and Neck Cancer. A Review

1992 ◽  
Vol 78 (5) ◽  
pp. 311-325 ◽  
Author(s):  
Carlo Fallai ◽  
Patrizia Olmi
Keyword(s):  
Total Dose ◽  
Head And Neck ◽  
Local Control ◽  
Randomized Trials ◽  
Treatment Time ◽  
Dose Intensity ◽  
Field Size ◽  
Overall Treatment Time ◽  
Altered Fractionation ◽  
Improvement In Survival

The authors review the main contributions of international literature to show the current status in clinical trials on unconventional fractionations of the dose in radiotherapy of head and neck cancers. Several clinical (but only a few randomized) trials have been conducted over the last 15 years using hyperfractionated (HF), accelerated (AF) or mixed (HF-AF) schedules. HF schedules have obtained promising results in terms of local control in comparison with conventional fractionation (CF) of the dose. Improvement in survival was also obtained by the random trials of Pinto and Sanchiz, whereas in EORTC trial no. 22791, the improvement in survival rate was only marginal. A significant increase in local control and, less frequently, in survival has been claimed in several studies using HF-AF. Such data still need to be confirmed by a random study, since EORTC trial 22811 showed superimposable results in comparison with CF. Selection of the most suitable cases for altered fractionation schemes is also being studied in ongoing trials of the EORTC (22851) and RTOG (90-03). As regards acute reactions during and after altered fractionation, they are more severe than after CF. Only pure HF with a dose intensity approximately comparable to CF seems to produce similar acute reactions. Several factors have been found to influence the severity of acute mucosal reactions: interfraction interval, overall treatment time, total dose, and field size. As regards late damage, genuine HF schemes seem to cause roughly equivalent late damage in comparison to CF, whereas high-dose intensity schedules have a higher rate of complications. Interfraction interval, overall treatment time, total dose, fraction size and field size can influence the risk of late sequelae. Before altered fractionations can be considered standard therapy, more data are needed, which should be provided by multicentric randomized trials, some of which are already in progress.

Treatment of cancer with radiation and drugs.

1996 ◽  
Vol 14 (12) ◽  
pp. 3156-3174 ◽  
Author(s):  
I F Tannock
Keyword(s):  
Randomized Trials ◽  
Combined Treatment ◽  
Therapeutic Index ◽  
Clinical Results ◽  
Therapeutic Benefit ◽  
Current Status ◽  
Combined Modality Treatment ◽  
Normal Tissues ◽  
Tissue Microenvironment ◽  
Meta Analyses

PURPOSE To review the current status and future prospects of combined treatment of cancer with radiation and drugs. DESIGN A review of (1) mechanisms whereby combined use of radiation and drugs might lead to improved therapeutic benefit for the treatment of cancer; (2) problems related to the design and analysis of clinical trials that evaluate combined modality treatment; and (3) clinical results of larger randomized trials that have compared combined versus single modality treatment for various types of cancer. RESULTS Improvement in the therapeutic index depends on exploitation of the biologic properties that differ between tumors and normal tissues; such properties may include mechanisms of resistance to radiation and drugs, tissue microenvironment, and cell proliferation or repopulation during radiotherapy. To detect or rule out the small but clinically important differences in outcome that might occur will require the performance of large, randomized, controlled trials or patient-based meta-analyses; single-arm studies, small randomized trials, and subgroup analyses of larger trials can generate hypotheses. Clinical gains from combined treatment have been demonstrated in a few sites, with disappointing results in others. In general, more promising results have accrued from concurrent treatment, despite greater toxicity, than from sequential use of drugs and radiation. CONCLUSION Clinical gains from combined treatment with radiation and drugs have been small. New, mechanistically based approaches to combined treatment are required.

Cetuximab versus cisplatin concurrent with IMRT in locally advanced head and neck cancer (LAHNC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e17030-e17030 ◽  
Author(s):  
S. L. Galper ◽  
H. Deshpande ◽  
M. G. Rose ◽  
R. H. Decker
Keyword(s):  
Treatment Time ◽  
Randomized Study ◽  
Locally Advanced ◽  
Late Toxicity ◽  
Distant Metastases ◽  
Overall Treatment Time ◽  
Tumor Registry ◽  
Altered Fractionation ◽  
N Stage

e17030 Background: Concurrent chemoradiation of LAHNC with cetuximab or cisplatin improves survival. The purpose of this study is to compare cetuximab chemoradiation (ExRT) with cisplatin chemoradiation (ChRT) in patients treated with IMRT. Methods: Between January 2005 and August 2008, 24 patients with LAHNC were treated with definitive chemoradiation utilizing IMRT. ExRT was reserved for those whose age or comorbidities precluded ChRT. 15 patients were treated with ChRT and 9 patients were treated with ExRT. Patient charts and Tumor Registry data were reviewed for acute and late toxicity and for local/regional failure (LRF), distant metastases and death. Results: The ExRT cohort was significantly older (median age 71 vs 58, p=0.005) and had more larynx/hypopharynx primaries (44% vs 27%). The cohorts were otherwise balanced with respect to T- and N-stage. Median follow-up for the ExRT and ChRT cohorts was 11 and 12 months, respectively. Overall treatment time in compliant patients was lower in ExRT patients (46 vs 50 days, p=0.05), reflecting increased use of accelerated radiation fractionation (66% vs 40%). See Table for toxicity outcomes. There was a trend toward increased ≥G3 acute mucositis in the ExRT group (p=0.07). However, there was less weight loss (p=0.05). There were similar acute epidermitis and hospitalizations for malnutrition/hydration rates and a nonsignificant decrease in prolonged mucosal toxicity. 1 patient developed skin necrosis and another osteoradionecrosis in the ChRT group. 1-year freedom from LRF was 89% in the ChRT group vs 56% in the ExRT group (p=0.07). Overall survival (OS) at 1 year was 100% (ChRT) vs 88% (ExRT). Conclusions: ExRT showed a trend toward worse acute mucosal toxicity but not late toxicity despite increased rates of altered fractionation with a higher daily dose. ExRT was associated with worse LRC and OS. A randomized study would best compare outcomes and toxicity profiles. Until such analysis, cetuximab should be reserved for patients unable to tolerate ChRT. [Table: see text] No significant financial relationships to disclose.

Critical impact of radiotherapy protocol compliance and quality in the treatment of retroperitoneal sarcomas: Results from the 62092-22092 STRASS trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11566-11566
Author(s):  
Rick L.M. Haas ◽  
Jean-Jacques Stelmes ◽  
Facundo Zaffaroni ◽  
Enrico Clementel ◽  
Raquel Bar Deroma ◽  
...  
Keyword(s):  
Treatment Time ◽  
Performance Status ◽  
Composite Endpoint ◽  
Target Volume ◽  
Phase Iii ◽  
Quality Assurance Program ◽  
Neoadjuvant Radiotherapy ◽  
Overall Treatment Time ◽  
Cancer Society ◽  
The Impact

11566 Background: The EORTC 22092-62092 STRASS trial failed to detect a superiority of neoadjuvant radiotherapy in patients with retroperitoneal sarcoma as compared to surgery alone. As radiotherapy (RT) was the experimental treatment, a comprehensive quality assurance program (RTQA) has been included in the study protocol in order to detect and correct potential RT deviations. We report here the overall trial RTQA results and its potential impact on patient’s outcomes in this international phase III trial. Methods: Plans from all patients randomized to the experimental preoperative RT arm were submitted to a multidisciplinary RTQA team, consisting of medical physicists and radiation-oncologists. Target volume parameters and tumor dose coverage were prospectively reviewed by the RTQA team but not all plans were made compliant. In order to evaluate the impact on oncological outcomes, a composite endpoint, overall RT compliance status, was created; patients were classified into two major groups: RT compliant (RC) group and non-compliant (NRC) group, defining whether RT was as concisely per protocol or not. This composite endpoint combined the information related to PTV coverage, target delineation, total dose received and overall treatment time. Both abdominal recurrence-free survival (ARFS) and OS were compared between RC and NRC patients using Cox’s proportional hazard model adjusted for age, sex, WHO performance status, tumor grade, histological subtype and tumor size at baseline (millimeters). Results: After final review, 75.2% (94 out of 125) of patients had compliant RT plans (65.6% were already compliant at first submission to RTQA team and 9.6% were made compliant after review). Most patients in the NRC (77.4%) had deviations linked to incorrect target volume delineations. 3-year ARFS was 67.2% (95% Confidence interval (CI): 58.0 – 77.8%) and 48.4% (34.3 – 68.2%) for RC and NRC group, respectively (adjusted HR: 2.64, 95% CI: 1.38 – 5.07, p = 0.003). Corresponding OS at 3 years was 89.9% (95% CI: 83.6 – 96.3%) and 75.4% (95% CI: 61.9 – 91.8%) in the RC and NRC group with a trend in favor of RC (adjusted HR: 2.76, 95% CI: 0.91 – 8.43, p = 0.074). Conclusions: To our knowledge, this is the first RTQA evaluation of a phase III sarcoma trial. The data suggests a significant benefit in terms of ARFS and a trend for OS in favor of the RT compliant group. RTQA in prospective clinical trials, investigating new RT techniques, dose levels and indications, continues to be an important and integral part of trial designing. Funding Source: EORTC, EORTC Cancer Research Fund, EUROSARC FP7 278472 and Kom op tegen Kanker (Stand up to Cancer), the Flemish Cancer Society.

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