Salvage reirradiation for local failure of prostate cancer after curative radiation therapy: Association of rectal toxicity with dose distribution and normal-tissue complication probability models

Abstract

PurposeThis study aimed to assess the impact of radiation dose on rectal toxicity after salvage external beam radiation therapy (EBRT) with or without a brachytherapy boost for exclusive local failures after the primary EBRT for prostate cancer.Methods and materialsFourteen patients with no severe residual late toxicity after primary EBRT ± brachytherapy were reirradiated after a median time interval of 6.1 years. The median normalized total dose in 2 Gy fractions (NTD2Gy, α/β ratio = 1.5 Gy for prostate cancer cells) was 74 Gy at primary EBRT and 85.1 Gy at reirradiation. Rectal dose-volume histograms (converted to NTD2Gy_alpha/beta = 3 Gy) and the corresponding normal-tissue complication probability (NTCP) values for gastrointestinal (GI) toxicity were evaluated for 2 groups: High GI toxicity (grade ≥3) and low GI toxicity (grade ≤2).ResultsThe 5-year grade ≥3 GI toxicity-free survival rate was 57.1%. The median rectal V70Gy and maximum dose to 1 cm3 (D1ccrect) at primary EBRT were both predictive for grade ≥3 GI toxicity (9% vs 0%; P = .04 and 72.2 Gy vs 66.8 Gy; P < .01, respectively). When adding primary radiation therapy (RT) and reirradiation plans, the median D1ccrect was 139.8 Gy versus 126.7 Gy (P < .01) for high and low GI toxicity groups. NTCP >10% at primary RT was predictive for high GI toxicity at reirradiation (P < .05).ConclusionsEven in the absence of residual toxicity after primary RT, rectal doses >70 Gy and NTCP >10% calculated for a first irradiation may be associated with a higher risk of developing high GI toxicity at reirradiation with a possible D1ccrect threshold of 130 Gy.

Assessing localized dosimetric effects due to unplanned gas cavities during pelvic MR‐guided radiotherapy using Monte Carlo simulations

“…Studies exploring dose‐volume rectal toxicity during EBRT have found that the risk of developing toxicity increases exponentially with the volume of rectal wall irradiated, with volumes of 1 cc receiving ≥70 Gy significantly increasing the risk of grade 2 or above late toxicity . Our results indicate that 1 cc of the rectal wall would receive 45% more dose than planned when a large unplanned gas cavity is present.…”

“…Studies exploring dose-volume rectal toxicity during EBRT have found that the risk of developing toxicity increases exponentially with the volume of rectal wall irradiated, with volumes of 1 cc receiving ≥70 Gy significantly increasing the risk of grade 2 or above late toxicity. [25][26][27][28] Our results indicate that 1 cc of the rectal wall would receive 45% more dose than planned when a large unplanned gas cavity is present. As it has been shown that limiting the D 1cc dose constraint to 55 Gy during pancreas chemoradiation reduces grade 2+ duodenal toxicity 47% to 9%, this approach could help to reduce risk of toxicity during MRgRT.…”

A Novel Salvage Option for Local Failure in Prostate Cancer, Reirradiation Using External Beam or Stereotactic Radiation Therapy: Systematic Review and Meta-Analysis

“…Only 1 study was prospective, 27 and the remainder were retrospective. Of the 6 articles meeting eligibility criteria but not included in the quantitative analysis, 5 studies contained a major amount of overlap with a larger and more recently published study population, 39 , 40 , 41 , 42 , 43 and 1 study further detailed toxicity of re-RT 44 of an otherwise included study. 28

Figure 1 Preferred reporting items for systematic reviews and meta-analyses diagram of study selection for our systematic review.

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“…A summary of organs at risk (OAR) constraints used for bladder and rectum is presented in Appendix E4 . Dose-volume histogram information in the cohort published by Zilli was analyzed by Dipasquale et al 44 to predict GI toxicity. This identified increasing cumulative D1cc (minimum dose to 1 cm³ of the most irradiated volume) to the rectum was associated with grade 3/4 GI toxicity, and staying below a combined threshold of 130 Gy (α/β= 3) may be a reasonable target.…”

Reirradiation for isolated local recurrence of prostate cancer: Mono-institutional series of 64 patients treated with salvage stereotactic body radiotherapy (SBRT)

“…For example, in the series presented by Loi et al, 1-year biochemical relapse-free survival was 80%, comparable with 85% 1-year biochemical progression free survival rate in our series when BED ≥130 Gy was administered. Nonetheless, we have to considered that most our patients received a relatively low dose at the first course of RT (median dose of 70.2 Gy), while for patients recently treated in the dose escalation era with higher BED at first treatment, the safe dose of re-EBRT still have to be defined, especially for the risk of late rectal toxicity 47.…”