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 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 Prolonged overall treatment time negatively affects the outcomes of stereotactic body radiotherapy for early-stage non-small-cell lung cancer: A propensity score-weighted, single-center analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253203
Author(s):  
Toshiki Ikawa ◽  
Takahiro Tabuchi ◽  
Koji Konishi ◽  
Masahiro Morimoto ◽  
Takero Hirata ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Propensity Score ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Stereotactic Body Radiotherapy ◽  
Treatment Time ◽  
Early Stage ◽  
Small Cell ◽  
Small Cell Lung ◽  
Overall Treatment Time

Previous studies have reported conflicting results for the effect of overall treatment time with stereotactic body radiotherapy on tumor control in early-stage non-small-cell lung cancer. To examine this effect, we conducted a propensity score-weighted, retrospective, observational study at a single institution. We analyzed the data of 200 patients with early-stage non-small-cell lung cancer who underwent stereotactic body radiotherapy (48 Gy in 4 fractions) at our institution between January 2007 and October 2013. Patients were grouped into consecutive (overall treatment time = 4–5 days, n = 116) or non-consecutive treatment groups (overall treatment time = 6–10 days, n = 84). The outcomes of interest were local control and overall survival. The Cox regression model was used with propensity score and inverse probability of treatment weighting. The median overall treatment times in the consecutive and non-consecutive groups were 4 and 6 days, respectively. The 5-year local control and overall survival rates in the consecutive vs. the non-consecutive group were 86.3 vs. 77.2% and 55.5 vs. 51.8%, respectively. After propensity score weighting, consecutive stereotactic body radiotherapy was associated with positive local control (adjusted hazard ratio 0.30, 95% confidence interval 0.14–0.65; p = 0.002) and overall survival (adjusted hazard ratio 0.56, 95% confidence interval 0.34–0.91; p = 0.019) benefits. The prolonged overall treatment time of stereotactic body radiotherapy treatment negatively affected the outcomes of patients with early-stage non-small-cell lung cancer. To our knowledge, this is the first study to show that in patients with early-stage non-small-cell lung cancer treated with the same dose-fractionation regimen, consecutive stereotactic body radiotherapy has a more beneficial effect on tumor control than non-consecutive stereotactic body radiotherapy.

PATRIOT Trial: Randomized phase II study of prostate stereotactic body radiotherapy comparing 11 versus 29 days overall treatment time.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 6-6 ◽  
Author(s):  
Harvey Charles Quon ◽  
Aldrich Ong ◽  
Patrick Cheung ◽  
William Chu ◽  
Hans T. Chung ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Stereotactic Body Radiotherapy ◽  
Treatment Time ◽  
Phase Ii Study ◽  
Overall Treatment Time ◽  
Randomized Phase Ii ◽  
Grade 3 ◽  
The Impact

6 Background: Stereotactic body radiotherapy (SBRT) for the treatment of prostate cancer is rapidly increasing. Reported regimens differ in time, dose, and fractionation. We report the results of a multicentre, Canadian randomized phase II study to investigate the impact of overall treatment time on quality of life (QOL) and toxicity. Methods: Men with cT1-2b, Gleason <=7, and PSA <= 20 ng/mL prostate cancer were randomly assigned to 40 Gy in 5 fractions delivered every other day (11 days) vs. once per week (29 days) using gantry-based SBRT. QOL was assessed using the Expanded Prostate Cancer Index Composite (EPIC) at baseline, weeks 2, 4, 6, 12, months 6 and 12, then annually. Toxicity was graded according to RTOG Criteria. The primary end point was the proportion of patients with a minimum clinically important change (MCIC) in bowel QOL at any time during the acute (<=12 week) period and was analyzed by Fisher’s exact test with a two-sided p < 0.05 considered significant. MCIC was defined as a decrease in EPIC score of >0.5 standard deviation of the baseline value. ClinicalTrials.gov NCT01423474. Results: 152 men from 3 centres were randomized with a median follow-up of 13.1 months. Baseline characteristics were similar in both arms except for the International Prostate Symptom Score with medians of 4 vs. 7 in the 11 and 29 day groups, respectively (p=0.02). There were significant differences between the 11 and 29 day groups in the proportion of patients with acute MCIC in bowel (90.0% vs. 69.6%, p<0.01) and urinary (95.7% vs. 74.6%, p<0.01) scores, respectively. No differences were found in acute sexual (p=0.38) or hormonal (p=0.48) QOL. Worst acute grade 1, 2, 3 toxicities were 64, 18, 0% vs. 41, 11, 0% (p<0.01) for GI and 38, 32, 1% vs. 30, 34, 3% (p=0.69) for GU in the 11 and 29 day groups, respectively. There were no late grade 3+ GI toxicities. Late grade 3 GU toxicity occurred in 1 vs. 0 patients in the 11 and 29 day arms (p=0.32). Conclusions: Prostate SBRT delivered over 29 days was associated with superior bowel and urinary QOL compared to 11 days in the first 3 months of treatment. There were few severe (grade 3+) toxicities in either group. Follow-up is continuing to compare long-term outcomes. Clinical trial information: NCT01423474.

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.

Twice- vs. thrice-weekly moderate hypofractionated radiotherapy for prostate cancer: does overall treatment time matter?

2019 ◽  
Vol 145 (6) ◽  
pp. 1581-1588
Author(s):  
Vérane Achard ◽  
Sandra Jorcano ◽  
Michel Rouzaud ◽  
Lluís Escudé ◽  
Raymond Miralbell ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Treatment Time ◽  
Hypofractionated Radiotherapy ◽  
Overall Treatment Time

scholarly journals Moderate Hypofractionated Protracted Radiation Therapy and Dose Escalation for Prostate Cancer: Do Dose and Overall Treatment Time Matter?

2016 ◽  
Vol 94 (2) ◽  
pp. 272-279 ◽  
Author(s):  
Melpomeni Kountouri ◽  
Thomas Zilli ◽  
Michel Rouzaud ◽  
Angèle Dubouloz ◽  
Dolors Linero ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiation Therapy ◽  
Dose Escalation ◽  
Treatment Time ◽  
Overall Treatment Time

Glioblastoma (GBM) in elderly patients: A randomized phase III trial comparing survival in patients treated with 6-week radiotherapy (RT) versus hypofractionated RT over 2 weeks versus temozolomide single-agent chemotherapy (TMZ).

2010 ◽  
Vol 28 (18_suppl) ◽  
pp. LBA2002-LBA2002 ◽  
Author(s):  
A. Malmstrom ◽  
B. H. Grønberg ◽  
R. Stupp ◽  
C. Marosi ◽  
D. Frappaz ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Survival Data ◽  
Treatment Time ◽  
Performance Status ◽  
Treatment Options ◽  
Single Agent ◽  
Tumor Resection ◽  
Phase Iii ◽  
Primary Study ◽  
Significant Difference

LBA2002 Background: Despite treatment advances, survival of elderly GBM patients (pts) is usually < 12 months. Hypofractionated RT is advocated in order to shorten treatment time, and chemotherapy has been proposed as an alternative to RT. In a randomized trial we compared two different RT schedules with single-agent TMZ chemotherapy. Methods: Newly diagnosed GBM pts age ≥ 60 years with PS 0-2, were randomized to either standard RT (60 Gy in 2 Gy fractions over 6 weeks) or hypofractionated RT (34 Gy in 3,4 Gy fractions over 2 weeks) or 6 cycles of chemotherapy with TMZ (200 mg/m2 day 1-5 every 28 days). Follow-up including quality of life, symptom checklist, and steroid dosing was completed at 6 weeks, 3 months, and 6 months after start of treatment. The primary study end point was overall survival (OS). Results: A total of 342 pts were included. 291 pts were randomized between the 3 treatment options, 51 pts between hypofractionated RT and TMZ. Median age was 70 years (range 60-88), 59% were male and 72% had undergone tumor resection, the remaining 28% had a diagnostic biopsy only. Performance status was 0-1 for 75% of pts. Survival data are available for 334 pts (98%), with 11 pts (3%) being alive. There was no significant difference in OS between the three treatment arms, with median survival being 8 months for TMZ, 7.5 months for hypofractionated RT and 6 months for 6 weeks RT (p=0.14). Conclusions: Elderly patients with GBM have a short survival. Time-consuming therapy that does not offer longer survival should therefore be avoided. Our study showed no advantage of standard 6 weeks RT compared to hypofractionated RT over 2 weeks or 6 cycles of TMZ chemotherapy. These results indicate that standard RT should no longer be offered to the elderly pt population with GBM. Exclusive TMZ chemotherapy may be an alternative to RT. Subgroup analyses and determination of molecular markers is ongoing. Whether outcome could be improved by concomitant chemoradiotherapy is subject of ongoing clinical trials. [Table: see text]

Phase I/II study on stereotactic hypofractionated once-weekly radiation therapy (SHORT) for localized prostate cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 130-130 ◽  
Author(s):  
Indranil Mallick ◽  
Moses Arunsingh ◽  
Sriram Prasath ◽  
B Arun ◽  
Paromita Roy ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
High Risk ◽  
Phase I ◽  
Treatment Time ◽  
Late Toxicity ◽  
Biochemical Control ◽  
Overall Treatment Time ◽  
Risk Patients ◽  
Prescription Dose

130 Background: The low α/β ratio of prostate cancer (PrCa) is well established. However, stereotactic hypofractionated radiotherapy (SRT) has been investigated primarily in highly selected patient populations with low-intermediate risk disease. We performed a clinical trial of SRT delivered in once-weekly fractions on an unselected cohort of patients with non-metastatic PrCa. Methods: In this Phase I/II study 30 patients with non-metastatic PrCa (multiparametric MRI cT1-4N0, M0, Gleason 6-10, PSA < = 60 ng/ml) were treated with SRT to a prescription dose of 35Gy in 5 fractions delivered once a week (overall treatment time 29 days). Elective nodal RT at 25Gy/5Fr was delivered in patients high-risk by NCCN criteria, and androgen deprivation therapy given to intermediate and high-risk patients. SRT was planned using volumetric intensity modulated arc therapy (VMAT) or Helical Tomotherapy (HT) with pre-defined dose-criteria. The primary endpoint was acute toxicity NCI CTC v4, and secondary endpoints were biochemical control and late toxicity. Results: Thirty patients completed treatment per-protocol. Stage T3, Gleason 8-10, and PSA > 10 was seen in 18 (60%), 7 (23%) and 24 (80%) respectively. Overall 20 (66.7%) were high-risk. Median of Mean PTV dose was 36Gy, and normal tissue constraints could be met in all patients (Table). Acute urinary toxicities (Gr 0: 1; Gr 1: 27; Gr 2: 1; Gr 3-4: 0) and acute rectal toxicities (Gr 0: 20; Gr 1: 10; Gr 2: 0; Gr 3-4: 0) were very modest. The mean IPSS scores at baseline, end of treatment and 3 months after treatment were 8.8, 14.7, and 9.9. With a median follow up of 23.7 months, the 2 year biochemical control was 96%. Late grade 2 rectal bleeding developed in 1 patient. Conclusions: Carefully planned stereotactic VMAT/HT based once-weekly SRT to a predominantly high-risk non-metastatic PrCa cohort was very well tolerated and found to be safe for clinical use. Preliminary biochemical control and late toxicity profiles are encouraging. Clinical trial information: CTRI/2016/02/006671. [Table: see text]

New advances in the diagnosis and management of hepatocellular carcinoma

BMJ ◽  
2020 ◽  
pp. m3544 ◽  
Author(s):  
Ju Dong Yang ◽  
Julie K Heimbach
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systemic Treatment ◽  
Early Stage ◽  
Treatment Options ◽  
Intermediate Stage ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Long Term Outcomes ◽  
Stage Disease

ABSTRACT Hepatocellular carcinoma is one of the leading causes of cancer related death in the world. Biannual surveillance for the disease in patients with cirrhosis and in high risk carriers of hepatitis B virus allows early stage cancer detection and treatment with good long term outcomes. Liver ultrasonography and serum α fetoprotein are the most commonly used surveillance tests. If suspicious results are found on the surveillance test, multiphasic computed tomography or magnetic resonance imaging should be undertaken to confirm the diagnosis of hepatocellular carcinoma. If radiologic tests show inconclusive results, liver biopsy or repeat imaging could be considered for confirmation of hepatocellular carcinoma. Management of the disease is complex. Patients should be evaluated by a multidisciplinary team, and the selection of treatment should consider factors such as tumor burden, severity of liver dysfunction, medical comorbidities, local expertise, and preference of patients. Early stage hepatocellular carcinoma is best managed by curative treatment, which includes resection, ablation, or transplantation. Patients with intermediate stage disease often receive locoregional treatment. Systemic treatment is reserved for patients with advanced disease. Several positive, phase III, randomized controlled trials have expanded the systemic treatment options for advanced hepatocellular carcinoma with promising long term outcomes, especially trials using combination treatments, which could also have eventual implications for the treatment of earlier stage disease.

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