Stereotactic body radiation therapy for melanoma and renal cell carcinoma: impact of single fraction equivalent dose on local control

<p>Abstract</p> <p>Background</p> <p>Melanoma and renal cell carcinoma (RCC) are traditionally considered less radioresponsive than other histologies. Whereas stereotactic body radiation therapy (SBRT) involves radiation dose intensification via escalation, we hypothesize SBRT might result in similar high local control rates as previously published on metastases of varying histologies.</p> <p>Methods</p> <p>The records of patients with metastatic melanoma (n = 17 patients, 28 lesions) or RCC (n = 13 patients, 25 lesions) treated with SBRT were reviewed. Local control (LC) was defined pathologically by negative biopsy or radiographically by lack of tumor enlargement on CT or stable/declining standardized uptake value (SUV) on PET scan. The SBRT dose regimen was converted to the single fraction equivalent dose (SFED) to characterize the dose-control relationship using a logistic tumor control probability (TCP) model. Additionally, the kinetics of decline in maximum SUV (SUV_max) were analyzed.</p> <p>Results</p> <p>The SBRT regimen was 40-50 Gy/5 fractions (n = 23) or 42-60 Gy/3 fractions (n = 30) delivered to lung (n = 39), liver (n = 11) and bone (n = 3) metastases. Median follow-up for patients alive at the time of analysis was 28.0 months (range, 4-68). The actuarial LC was 88% at 18 months. On univariate analysis, higher dose per fraction (p < 0.01) and higher SFED (p = 0.06) were correlated with better LC, as was the biologic effective dose (BED, p < 0.05). The actuarial rate of LC at 24 months was 100% for SFED ≥45 Gy v 54% for SFED <45 Gy. TCP modeling indicated that to achieve ≥90% 2 yr LC in a 3 fraction regimen, a prescription dose of at least 48 Gy is required. In 9 patients followed with PET scans, the mean pre-SBRT SUV_maxwas 7.9 and declined with an estimated half-life of 3.8 months to a post-treatment plateau of approximately 3.</p> <p>Conclusions</p> <p>An aggressive SBRT regimen with SFED ≥ 45 Gy is effective for controlling metastatic melanoma and RCC. The SFED metric appeared to be as robust as the BED in characterizing dose-response, though additional studies are needed. The LC rates achieved are comparable to those obtained with SBRT for other histologies, suggesting a dominant mechanism of in vivo tumor ablation that overrides intrinsic differences in cellular radiosensitivity between histologic subtypes.</p

The role of whole brain radiation therapy in the management of newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline

QUESTION: Should patients with newly-diagnosed metastatic brain tumors undergo open surgical resection versus whole brain radiation therapy (WBRT) and/or other treatment modalities such as radiosurgery, and in what clinical settings? TARGET POPULATION: These recommendations apply to adults with a newly diagnosed single brain metastasis amenable to surgical resection. RECOMMENDATIONS: Surgical resection plus WBRT versus surgical resection alone Level 1 Surgical resection followed by WBRT represents a superior treatment modality, in terms of improving tumor control at the original site of the metastasis and in the brain overall, when compared to surgical resection alone. Surgical resection plus WBRT versus SRS + or - WBRT Level 2 Surgical resection plus WBRT, versus stereotactic radiosurgery (SRS) plus WBRT, both represent effective treatment strategies, resulting in relatively equal survival rates. SRS has not been assessed from an evidence-based standpoint for larger lesions (\u3e3 cm) or for those causing significant mass effect (\u3e1 cm midline shift). Level 3 Underpowered class I evidence along with the preponderance of conflicting class II evidence suggests that SRS alone may provide equivalent functional and survival outcomes compared with resection + WBRT for patients with single brain metastases, so long as ready detection of distant site failure and salvage SRS are possible. Note The following question is fully addressed in the WBRT guideline paper within this series by Gaspar et al. Given that the recommendation resulting from the systematic review of the literature on this topic is also highly relevant to the discussion of the role of surgical resection in the management of brain metastases, this recommendation has been included below

Forest bat population dynamics over 14 years at a climate refuge: Effects of timber harvesting and weather extremes

<div><p>Long-term data are needed to explore the interaction of weather extremes with habitat alteration; in particular, can ‘refugia’ buffer population dynamics against climate change and are they robust to disturbances such as timber harvesting. Because forest bats are good indicators of ecosystem health, we used 14 years (1999–2012) of mark-recapture data from a suite of small tree-hollow roosting bats to estimate survival, abundance and body condition in harvested and unharvested forest and over extreme El Niño and La Niña weather events in southeastern Australia. Trapping was replicated within an experimental forest, located in a climate refuge, with different timber harvesting treatments. We trapped foraging bats and banded 3043 with a 32% retrap rate. Mark-recapture analyses allowed for dependence of survival on time, species, sex, logging treatment and for transients. A large portion of the population remained resident, with a maximum time to recapture of nine years. The effect of logging history (unlogged vs 16–30 years post-logging regrowth) on apparent survival was minor and species specific, with no detectable effect for two species, a positive effect for one and negative for the other. There was no effect of logging history on abundance or body condition for any of these species. Apparent survival of residents was not strongly influenced by weather variation (except for the smallest species), unlike previous studies outside of refugia. Despite annual variation in abundance and body condition across the 14 years of the study, no relationship with extreme weather was evident. The location of our study area in a climate refuge potentially buffered bat population dynamics from extreme weather. These results support the value of climate refugia in mitigating climate change impacts, though the lack of an external control highlights the need for further studies on the functioning of climate refugia. Relatively stable population dynamics were not compromised by timber harvesting, suggesting ecologically sustainable harvesting may be compatible with climate refugia.</p></div

Time varying survival parameters and their covariate (MaxTempSumm).

<p>The value plotted over year <i>n (n</i> = 1999–2011) is survival over the year beginning with the capture event of year <i>n</i> to year <i>n</i>+1. VrU = <i>V</i>. <i>regulus</i> in unlogged; VpM = <i>V</i>. <i>pumilus</i> males; VpFU = <i>V</i>. <i>pumilus</i> females in unlogged. Note that survival values are averages over modelled estimates assuming covariation with the weather covariates.</p

Plots of estimated abundance (●) and number of residents (▲) over all four species per site with respect to capture event, numbered as in Fig 3.

<p>Plots of estimated abundance (●) and number of residents (▲) over all four species per site with respect to capture event, numbered as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0191471#pone.0191471.g003" target="_blank">Fig 3</a>.</p

Survival structure in model φ(1)p(sex+ MaxTempSumm + AvMinTempDur).

<p>The two-letter species abbreviation indicate survival rates for that species, qualified if the rate was sex specific by adding M or F and treatment specific by adding R(regrowth) or U (unlogged), e.g., CmFU, designates a survival rate for female <i>Chalinolobus morio</i> in unlogged treatments. The absence of a qualifier means the survival rate is independent of that effect. Coincidences between survival rates are expressed with equality signs. All the survival parameters in the second column were modelled as logistic regressions on the covariate MaxTempSumm with the same regression coefficient but their own intercept, independently of whether they were newly or already marked. Note that survival rates <i>within the same year</i> only apply to the capture season, and should not be extrapolated beyond this period.</p

High elevation eucalypt forest in the climate refuge study area.

<p>(a) unlogged forest catchment showing tall emergent eucalypts above a dense rainforest understorey (b) 27 year old regrowth catchment showing dense stands of mixed eucalypts and rainforest species with a small 4WD trail used for harp-trapping bats.</p

Capture frequency and counts of individual bats per species (18 of these captures occurred in 2012, the final capture event, and eight marked bats were not re-released (deaths) at earlier capture events, so of 2087 captures, 26 did not constitute releases).

<p>Capture frequency and counts of individual bats per species (18 of these captures occurred in 2012, the final capture event, and eight marked bats were not re-released (deaths) at earlier capture events, so of 2087 captures, 26 did not constitute releases).</p

Covariates employed in modelling time dependence in survival and recapture.

<p>Covariates employed in modelling time dependence in survival and recapture.</p