PMID- 27014930
OWN - NLM
STAT- MEDLINE
DCOM- 20190513
LR  - 20201029
IS  - 1537-453X (Electronic)
IS  - 0277-3732 (Print)
IS  - 0277-3732 (Linking)
VI  - 41
IP  - 4
DP  - 2018 Apr
TI  - Impact of Radiation Therapy Dose Escalation on Prostate Cancer Outcomes and 
      Toxicities.
PG  - 409-415
LID - 10.1097/COC.0000000000000285 [doi]
AB  - OBJECTIVES: Freedom from biochemical failure (FFBF) is a common primary outcome 
      of randomized-controlled trials of prostate cancer (PCa). We aimed to determine 
      how increasing the PCa biologically equivalent dose (BED) of external radiation 
      therapy (RT) is correlated with FFBF and overall patient outcomes: overall 
      survival (OS), distant metastasis (DM), and cancer-specific mortality (CSM); as 
      well as genitourinary (GU), and gastrointestinal toxicities. MATERIALS AND 
      METHODS: We performed a meta-analysis of 6884 PCa patients from 12 
      randomized-controlled trials of external beam RT. Mixed effects regression models 
      were used to estimate weighted linear relationships between BED and observed 
      percentages of 5- and 10-year outcomes. For toxicities, a subset analysis of 
      using 3-dimensional conformal RT (3D-CRT) versus intensity-modulated RT (IMRT) 
      was performed. RESULTS: Increasing BED correlated with improved FFBF: 10-year 
      absolute improvement of 9.6% and 7.2% for low-risk and intermediate-risk 
      patients, respectively (P<0.05); but not with improvement of OS, DM, or CSM at 
      either time point. BED escalation was not correlated with increased acute 
      toxicities; it was correlated with increased late gastrointestinal toxicities in 
      patients treated with 3D-CRT (1.5% increase over BED range, P<0.01). IMRT 
      patients had significantly fewer late toxicities, despite being treated at higher 
      BED. CONCLUSIONS: RT BED escalation has resulted in significantly improved PCa 
      FFBF at up to 10 years; but not with improvement in OS, DM, or CSM. Thus, FFBF is 
      a poor surrogate of overall patient outcomes for trials of RT. Late toxicities 
      were less frequent with IMRT than with 3D-CRT, even at higher BED.
FAU - Zaorsky, Nicholas G
AU  - Zaorsky NG
AD  - Department of Radiation Oncology, Fox Chase Cancer Center.
FAU - Keith, Scott W
AU  - Keith SW
AD  - Department of Pharmacology and Experimental Therapeutics, Division of 
      Biostatistics.
FAU - Shaikh, Talha
AU  - Shaikh T
AD  - Department of Radiation Oncology, Fox Chase Cancer Center.
FAU - Nguyen, Paul L
AU  - Nguyen PL
AD  - Department of Radiation Oncology, Brigham and Women's Hospital, Boston, MA.
FAU - Horwitz, Eric M
AU  - Horwitz EM
AD  - Department of Radiation Oncology, Fox Chase Cancer Center.
FAU - Dicker, Adam P
AU  - Dicker AP
AD  - Department of Radiation Oncology, Sidney Kimmel Medical College at Thomas 
      Jefferson University, Philadelphia, PA.
FAU - Den, Robert B
AU  - Den RB
AD  - Department of Radiation Oncology, Sidney Kimmel Medical College at Thomas 
      Jefferson University, Philadelphia, PA.
LA  - eng
GR  - P30 CA006927/CA/NCI NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Am J Clin Oncol
JT  - American journal of clinical oncology
JID - 8207754
SB  - IM
MH  - Humans
MH  - Male
MH  - Meta-Analysis as Topic
MH  - Prognosis
MH  - Prospective Studies
MH  - Prostatic Neoplasms/*mortality/*radiotherapy
MH  - Radiation Injuries/etiology/*mortality
MH  - Radiotherapy Dosage
MH  - Radiotherapy, Conformal/adverse effects/*mortality
MH  - Radiotherapy, Intensity-Modulated/adverse effects/*mortality
MH  - Survival Rate
PMC - PMC7592421
MID - NIHMS1635046
COIS- Conflicts of Interest Notification: We have no conflicts of interests.
EDAT- 2016/03/26 06:00
MHDA- 2019/05/14 06:00
PMCR- 2020/10/28
CRDT- 2016/03/26 06:00
PHST- 2016/03/26 06:00 [pubmed]
PHST- 2019/05/14 06:00 [medline]
PHST- 2016/03/26 06:00 [entrez]
PHST- 2020/10/28 00:00 [pmc-release]
AID - 10.1097/COC.0000000000000285 [doi]
PST - ppublish
SO  - Am J Clin Oncol. 2018 Apr;41(4):409-415. doi: 10.1097/COC.0000000000000285.