Seagrass habitats provide important ecosystem services, including their ability to take up and store substantial amounts of organic carbon, known as 'blue carbon.' However, the paucity of geospatial ...and carbon storage information along the Pacific Coast of Canada hinders the inclusion of blue carbon storage data in conservation planning and policy development in coastal habitats. We assessed the carbon storage and accumulation rates in three eelgrass (Zostera marina) meadows in southern Clayoquot Sound on the Pacific Coast of British Columbia. The intertidal and subtidal portions of each meadow were mapped and sampled to estimate eelgrass density, biomass, and carbon, and sediment cores were analyzed to estimate sediment carbon storage and accumulation rates. Aboveground biomass measurements were consistent with estimates for Z. marina in other regions, with average aboveground carbon biomass estimates of 16.78 g C m-2 and 16.25 g C m-2 in the intertidal and subtidal areas, respectively. However, the estimated aboveground to belowground biomass ratio was an order of magnitude higher than for seagrass species in temperate/tropical areas, largely because belowground biomass was up to 10 times lower than for other Z. marina meadows, averaging 6.17 g C m-2 and 5.03 g C m-2 in the intertidal and subtidal zones, respectively. Sediment carbon concentrations did not exceed 1.30%Corg, and carbon accumulation rates ranged from 2.90-39.61 g Corg m-2 yr-1, decreasing with depth and averaging 10.8 ± 5.2 g Corg m-2 yr-1. While sediment carbon stocks were generally higher in the eelgrass meadows relative to non-vegetated reference sites, carbons stocks averaged 1343 ± 482 g Corg m-2, substantially less than global averages. These carbon results confirm that eelgrass does contribute to carbon storage in Clayoquot Sound but at lower rates than identified for more tropical seagrasses. By improving the quantification of site-specific carbon dynamics, eelgrass' role in climate change mitigation and conservation planning can be assessed.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In the randomized trial of standard- versus high-dose chemoradiotherapy for locally advanced (LA) NSCLC (Radiation Therapy Oncology Group 0617), overall survival (OS) was worse in the high-dose arm. ...Although heart dose was suggested as a contributing factor, actionable parameters have not been established. We present an analysis of clinical and dosimetric parameters affecting OS in this patient population, focusing on heart dose.
Clinical data were collected on 416 patients with LA NSCLC treated at a single institution, with a subset of 333 available treatment plans recontoured using Radiation Therapy Oncology Group 0617 normal tissue guidelines. Toxicity and dosimetry data were analyzed for 322 patients; multivariate analysis was performed on 251 patients. Dosimetric parameters of radiation to tumor and organs at risk were analyzed with clinical data pertaining to OS, disease-free survival, and toxicity.
Patients were treated with radiation therapy to prescribed doses of 50.0 to 84.9 Gy (median 66.0 Gy). Median follow-up was 14.5 months. Median OS was 16.8 months. The 1- and 2-year OS rates were 61.4% and 38.8%, respectively. On multivariate analysis, factors independently associated with worse OS were increasing heart V50 (volume receiving ≥50 Gy), heart volume, lung V5 (proportion of the lung structure excluding the target volume) receiving at least 5 Gy), bilateral mediastinal lymph node involvement, and lack of concurrent chemotherapy. When stratified by heart V50 less than 25% versus 25% or greater, the 1-year OS rates were 70.2% versus 46.8% and the 2-year OS rates were 45.9% versus 26.7% (p < 0.0001). Median heart V50 was significantly higher (20.8% versus 13.9%, p < 0.0001) for patients with cardiac toxicity with a Common Terminology Criteria for Adverse Events grade of 1 or higher.
Heart dose is associated with OS and cardiac toxicity for patients with LA NSCLC treated with chemoradiotherapy.
To determine patient, tumor, and treatment factors related to the development of late chest wall toxicity after lung stereotactic body radiotherapy (SBRT).
We reviewed a registry of 134 patients ...treated with lung SBRT to 60 Gy in 3 fractions who had greater than 1 year of clinical follow-up and no history of multiple treatments to the same lobe (n = 48). Patients were treated as per Radiation Therapy Oncology Group Protocol 0236 without specific chest wall avoidance criteria. The chest wall was retrospectively contoured. Thirty-two lesions measured less than 3 cm, and sixteen measured 3 to 5 cm. The median planning target volume was 29 cm(3).
With a median follow-up of 18.8 months, 10 patients had late symptomatic chest wall toxicity (4 Grade 1 and 6 Grade 2) at a median of 8.8 months after SBRT. No patient characteristics (age, diabetes, hypertension, peripheral vascular disease, or body mass index) were predictive for toxicity, whereas there was a trend for continued smoking (p = 0.066; odds ratio OR, 4.4). Greatest single tumor dimension (p = 0.047; OR, 2.63) and planning target volume (p = 0.040; OR, 1.04) were correlated with toxicity, whereas distance from tumor edge to chest wall and gross tumor volume did not reach statistical significance. Volumes of chest wall receiving 30 Gy (V30) through 70 Gy (V70) were all highly significant, although this correlation weakened for V65 and V70 and maximum chest wall point dose only trended to significance (p = 0.06). On multivariate analysis, tumor volume was no longer correlated with toxicity and only V30 through V60 remained statistically significant.
Tumor size and chest wall dosimetry are correlated to late chest wall toxicity. Only chest wall V30 through V60 remained significant on multivariate analysis. Restricting V30 to 30 cm(3) or less and V60 to 3 cm(3) or less should result in a 10% to 15% risk of late chest wall toxicity or lower.
Data on prevalence of brain metastases at presentation in patients with non–small-cell lung cancer are limited. We queried the National Cancer Data Base to determine prevalence, risk factors and ...outcomes of patients with non–small-cell lung cancer, presenting with brain metastases. Brain metastases were observed in 10.4% of patients, with median survival of 6 months. Risk of brain metastases at presentation may be calculated using 5 clinical variables.
Data on the prevalence of brain metastases at presentation in patients with non–small-cell lung cancer (NSCLC) are limited. We queried the National Cancer Data Base to determine prevalence, clinical risk factors, and outcomes of patients with NSCLC presenting with brain metastases.
Patients with NSCLC diagnosed between 2010 and 2012 were identified using the National Cancer Data Base. The risk of brain metastases for individual variables was summarized by odds ratios and calculated using logistic regression analysis. The Kaplan-Meier product limit method was used to calculate the median and 1-, 2-, and 3-year overall survival (OS).
Brain metastases were observed in 47,546 (10.4%) of the 457,481 patients with NSCLC overall. The prevalence of brain metastases was much higher (26%) in patients with stage IV disease at presentation. On multivariate analysis, younger age, adenocarcinoma or large cell histology, tumor size > 3 cm, tumor grade ≥ II, and node-positive disease were associated with brain metastases. The prevalence of brain metastases ranged from as low as 0.57% in patients with only 1 risk factor to as high as 22% in patients with all 5 risk factors. The median and 1-, 2-, and 3-year OS for patients with brain metastases were 6 months and 29.9%, 14.3%, and 8.4%, respectively, with the 3-year OS increasing to 36.2% in those with T1/2 and N0/1 undergoing surgery for the primary site.
In patients with NSCLC, the risk of brain metastases at presentation may be calculated based on 5 clinical variables. Selected patients with brain metastases at presentation may achieve prolonged benefit.
Summary Background We aimed to compare overall survival after standard-dose versus high-dose conformal radiotherapy with concurrent chemotherapy and the addition of cetuximab to concurrent ...chemoradiation for patients with inoperable stage III non-small-cell lung cancer. Methods In this open-label randomised, two-by-two factorial phase 3 study in 185 institutions in the USA and Canada, we enrolled patients (aged ≥18 years) with unresectable stage III non-small-cell lung cancer, a Zubrod performance status of 0–1, adequate pulmonary function, and no evidence of supraclavicular or contralateral hilar adenopathy. We randomly assigned (1:1:1:1) patients to receive either 60 Gy (standard dose), 74 Gy (high dose), 60 Gy plus cetuximab, or 74 Gy plus cetuximab. All patients also received concurrent chemotherapy with 45 mg/m2 paclitaxel and carboplatin once a week (AUC 2); 2 weeks after chemoradiation, two cycles of consolidation chemotherapy separated by 3 weeks were given consisting of paclitaxel (200 mg/m2 ) and carboplatin (AUC 6). Randomisation was done with permuted block randomisation methods, stratified by radiotherapy technique, Zubrod performance status, use of PET during staging, and histology; treatment group assignments were not masked. Radiation dose was prescribed to the planning target volume and was given in 2 Gy daily fractions with either intensity-modulated radiation therapy or three-dimensional conformal radiation therapy. The use of four-dimensional CT and image-guided radiation therapy were encouraged but not necessary. For patients assigned to receive cetuximab, 400 mg/m2 cetuximab was given on day 1 followed by weekly doses of 250 mg/m2 , and was continued through consolidation therapy. The primary endpoint was overall survival. All analyses were done by modified intention-to-treat. The study is registered with ClinicalTrials.gov , number NCT00533949. Findings Between Nov 27, 2007, and Nov 22, 2011, 166 patients were randomly assigned to receive standard-dose chemoradiotherapy, 121 to high-dose chemoradiotherapy, 147 to standard-dose chemoradiotherapy and cetuximab, and 110 to high-dose chemoradiotherapy and cetuximab. Median follow-up for the radiotherapy comparison was 22·9 months (IQR 27·5–33·3). Median overall survival was 28·7 months (95% CI 24·1–36·9) for patients who received standard-dose radiotherapy and 20·3 months (17·7–25·0) for those who received high-dose radiotherapy (hazard ratio HR 1·38, 95% CI 1·09–1·76; p=0·004). Median follow-up for the cetuximab comparison was 21·3 months (IQR 23·5–29·8). Median overall survival in patients who received cetuximab was 25·0 months (95% CI 20·2–30·5) compared with 24·0 months (19·8–28·6) in those who did not (HR 1·07, 95% CI 0·84–1·35; p=0·29). Both the radiation-dose and cetuximab results crossed protocol-specified futility boundaries. We recorded no statistical differences in grade 3 or worse toxic effects between radiotherapy groups. By contrast, the use of cetuximab was associated with a higher rate of grade 3 or worse toxic effects (205 86% of 237 vs 160 70% of 228 patients; p<0·0001). There were more treatment-related deaths in the high-dose chemoradiotherapy and cetuximab groups (radiotherapy comparison: eight vs three patients; cetuximab comparison: ten vs five patients). There were no differences in severe pulmonary events between treatment groups. Severe oesophagitis was more common in patients who received high-dose chemoradiotherapy than in those who received standard-dose treatment (43 21% of 207 patients vs 16 7% of 217 patients; p<0·0001). Interpretation 74 Gy radiation given in 2 Gy fractions with concurrent chemotherapy was not better than 60 Gy plus concurrent chemotherapy for patients with stage III non-small-cell lung cancer, and might be potentially harmful. Addition of cetuximab to concurrent chemoradiation and consolidation treatment provided no benefit in overall survival for these patients. Funding National Cancer Institute and Bristol-Myers Squibb.
Maps of nearshore marine habitat are fundamental tools for the management and conservation of coastal ecosystems. While traditional field mapping techniques, such as towed video and diver surveys, ...are still commonly employed for generating highly detailed maps of seafloor habitat, acoustic and satellite remote sensing have proven to be efficient alternatives for generating habitat maps. To date remote sensing using satellite imagery has dominated mapping efforts over coral reefs and other tropical ecosystems with fewer studies applied in temperate marine regions where acoustic studies are more common. Few studies exist that have assessed the performance of high resolution satellite imagery in mapping seafloor habitat in temperate regions. This paper compares the efficacy of high resolution satellite imagery (WorldView-2) and a single-beam acoustic ground discrimination system (QTC View V) for mapping the distribution of submerged aquatic vegetation at a site within the Gwaii Haanas National Marine Conservation Area (GHNMCA) off the north coast of British Columbia, Canada. Ground-truth data for training and validation were collected using a towed underwater video camera. Prior to classification the WorldView-2 image (8 bands, 2m resolution) was processed following orthorectification, atmospheric correction, glint correction, land and optically deep water masking. An acoustic survey was conducted using a 200kHz echosounder and data were processed and interpolated using QTC IMPACT software. The WorldView-2 imagery performed best in mapping habitat in regions shallower than 3m, obtaining a total accuracy 75%, where it could identify the distribution of green algae (Ulva spp.), brown algae (Fucus spp.) and eelgrass (Zostera marina). The 200kHz data were unable to detect the distribution of brown and green algae but were able to map the distribution of eelgrass as well as a subtidal red algae (Chondrocanthus exasperatus) (total accuracy 80%). A final habitat map containing all habitat types present at the study site was produced using the output from both datasets. The study resulted in recommendations for remote mapping of submerged vegetation in temperate coastal area.
•WV2 performed best in <3.0m depth. Able to detect eelgrass, brown and green algae•QTC5 system was capable of mapping the extent of eelgrass and subtidal red algae.•WV2: greater thematic accuracy but limited by cloud cover, depth and tidal condition•QTC5: extensive field data collection but more capable of mapping subtidal habitats
Prolonged radiation treatment (RT) time (RTT) has been associated with worse survival in several malignancies. The present study investigated whether delays during RT are associated with overall ...survival (OS) in non-small cell lung cancer (NSCLC).
The National Cancer Database was queried for patients with stage III NSCLC who had received definitive concurrent chemotherapy and fractionated RT to standard doses (59.4-70.0 Gy) and fractionation from 2004 to 2013. The RTT was classified as standard or prolonged for each treatment regimen according to the radiation dose and number of fractions. Cox proportional hazards models were used to evaluate the association between the following factors and OS: RTT, RT fractionation, demographic and pathologic factors, and chemotherapeutic agents.
Of 14,154 patients, the RTT was prolonged in 6262 (44.2%). Factors associated with prolonged RTT included female sex (odds ratio OR 1.21, P<.0001), black race (OR 1.20, P=.001), nonprivate health insurance (OR 1.30, P<.0001), and lower income (<$63,000 annually, OR 1.20, P<.0001). The median OS was significantly worse for patients with prolonged RTT than that for those with standard RTT (18.6 vs 22.7 months, P<.0001). Furthermore, the OS worsened with each cumulative interval of delay (standard RTT vs prolonged 1-2 days, 20.5 months, P=.009; prolonged 3-5 days, 17.9 months, P<.0001; prolonged 6-9 days, 17.7 months, P<.0001; prolonged >9 days, 17.1 months, P<.0001). On multivariable analysis, prolonged RTT was independently associated with inferior OS (hazard ratio 1.21, P<.0001). Prolonged RTT as a continuous variable was also significantly associated with worse OS (hazard ratio 1.001, P=.0007).
Delays during RT appear to negatively affect survival for patients with locally advanced NSCLC. We have detailed the demographic and socioeconomic barriers influencing prolonged RTT as a method to address the health disparities in this regard. Cumulative interruptions of RT should be minimized.
We report results from a prospective phase I/II trial for patients with centrally located, early-stage NSCLC receiving stereotactic body radiation therapy.
Eligible patients were medically inoperable ...with biopsy-proven NSCLC within 2 cm of the proximal bronchial tree or 5 mm of the mediastinal pleura or parietal pericardium. Phase I had four dose levels using 5 fractions: 9, 10, 11, and 12 Gy per fraction. The primary phase II objective was to determine if the maximum tolerated dose in phase I achieved local control greater than 80% at 2 years.
Seventy-four patients were enrolled; 23 to phase I and 51 to phase II. Two phase I patients treated with 10 Gy × 5 fractions developed unrelated acute grade 3 lung toxicities which resolved. The phase II dose level selected was 11 Gy × 5 fractions. The median follow-up for living phase II patients was 27 months (range, 9 to 58 months). Two-year local control using 11 Gy × 5 fractions was 85% (95% confidence interval CI: 62%–95%). Two-year overall survival was 43% (95% CI: 28%–57%). Three patients (6%, 95% CI: 1%–17%) experienced acute grade 3 and 4 cardiac or pulmonary toxicities. Of the 41 patients evaluable for late cardiac and pulmonary toxicity, 11 (27%, 95% CI: 14%–43%) developed grade 3, 5 (12%, 95% CI: 4%–26%) developed grade 4, and 1 (4%, 95% CI: 0%–13%) died of grade 5 toxicity.
Stereotactic body radiation therapy for central NSCLC using 11 Gy × 5 fractions is tolerable and has excellent local control, but is associated severe late toxicity in some patients.
To investigate the impact of modern postoperative radiotherapy (PORT) on overall survival (OS) for patients with N2 non-small-cell lung cancer (NSCLC) treated nationally with surgery and adjuvant ...chemotherapy.
Patients with pathologic N2 NSCLC who underwent complete resection and adjuvant chemotherapy from 2006 to 2010 were identified from the National Cancer Data Base and stratified by use of PORT (≥ 45 Gy). A total of 4,483 patients were identified (PORT, n = 1,850; no PORT, n = 2,633). The impact of patient and treatment variables on OS was explored using Cox regression.
Median follow-up time was 22 months. On univariable analysis, improved OS correlated with younger age, treatment at an academic facility, female sex, urban population, higher income, lower Charlson comorbidity score, smaller tumor size, multiagent chemotherapy, resection with at least a lobectomy, and PORT. On multivariable analysis, improved OS remained independently predicted by younger age, female sex, urban population, lower Charlson score, smaller tumor size, multiagent chemotherapy, resection with at least a lobectomy, and PORT (hazard ratio, 0.886; 95% CI, 0.798 to 0.988). Use of PORT was associated with an increase in median and 5-year OS compared with no PORT (median OS, 45.2 v 40.7 months, respectively; 5-year OS, 39.3% 95% CI, 35.4% to 43.5% v 34.8% 95% CI, 31.6% to 38.3%, respectively; P = .014).
For patients with N2 NSCLC after complete resection and adjuvant chemotherapy, modern PORT seems to confer an additional OS advantage beyond that achieved with adjuvant chemotherapy alone.
Definitive treatment of locally advanced non–small-cell lung cancer with radiation is challenging. During the course of treatment, anatomical changes such as tumor regression, tumor ...displacement/deformation, pleural effusion, and/or atelectasis can result in a deviation of the administered radiation dose from the intended prescribed treatment and thereby worsen local control and toxicity. Adaptive radiotherapy can help correct for these changes and can be generally categorized into 3 philosophical paradigms: (1) maintenance of prescribed dose to the initially defined target volume; (2) dose reduction to healthy organs while maintaining initial prescribed dose to a regressing tumor volume; or (3) dose escalation to a regressing tumor volume with isotoxicity to healthy organs. Numerous single institution studies have investigated these methods, and results from large prospective clinical trials will hopefully provide consensus on the method, utility, and efficacy of implementing adaptive radiation therapy (ART) in a clinical setting. Additional development into standardization and automation of the ART workflow, specifically in identifying when ART is warranted and in reducing the manual clinical effort needed to produce an adaptive plan, will be paramount to making ART feasible for the broader radiation therapy community.
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