Institutional experience in the treatment of colorectal liver metastases with stereotactic body radiation therapy

AimTo investigate whether the impact of dose escalation in our patient population represented an improvement in local control without increasing treatment related toxicity.Materials and methodsA cohort of consecutive patients with colorectal liver metastases treated with stereotactic body radiation therapy (SBRT) between December 2002 and December 2013 were eligible for this study. Inclusion criteria were a Karnofsky performance status ≥80% and, according to the multidisciplinary tumor board, ineligibility for surgery or radiofrequency ablation. Exclusion criteria were a lesion size >6[[ce:hsp sp="0.25"/]]cm, more than 3 metastases, and treatment delivered with other fractionation scheme than 3 times 12.5[[ce:hsp sp="0.25"/]]Gy or 16.75[[ce:hsp sp="0.25"/]]Gy prescribed at the 65–67% isodose. To analyze local control, CT or MRI scans were acquired during follow-up. Toxicity was scored using the Common Toxicity Criteria Adverse Events v4.0.ResultsA total of 40 patients with 55 colorectal liver metastases were included in this study. We delivered 37.5[[ce:hsp sp="0.25"/]]Gy to 32 lesions, and 50.25[[ce:hsp sp="0.25"/]]Gy to 23 lesions. Median follow-up was 26 and 25 months for these two groups. Local control at 2 and 3 years was 74 and 66% in the low dose group while 90 and 81% was reached in the high dose group. No significant difference in local control between the two dose fractionation schemes could be found. Grade 3 toxicity was limited and was not increased in the high dose group.ConclusionsSBRT for colorectal liver metastases offers a high chance of local control at long term. High irradiation doses may contribute to enhance this effect without increasing toxicity

A method to assess the clinical significance of unclassified variants in the BRCA1 and BRCA2 genes based on cancer family history

Introduction Unclassified variants (UVs) in the BRCA1/BRCA2 genes are a frequent problem in counseling breast cancer and/or ovarian cancer families. Information about cancer family history is usually available, but has rarely been used to evaluate UVs. The aim of the present study was to identify which is the best combination of clinical parameters that can predict whether a UV is deleterious, to be used for the classification of UVs. Methods We developed logistic regression models with the best combination of clinical features that distinguished a positive control of BRCA pathogenic variants (115 families) from a negative control population of BRCA variants initially classified as UVs and later considered neutral (38 families). Results The models included a combination of BRCAPRO scores, Myriad scores, number of ovarian cancers in the family, the age at diagnosis, and the number of persons with ovarian tumors and/ or breast tumors. The areas under the receiver operating characteristic curves were respectively 0.935 and 0.836 for the BRCA1 and BRCA2 models. For each model, the minimum receiver operating characteristic distance (respectively 90% and 78% specificity for BRCA1 and BRCA2) was chosen as the cutoff value to predict which UVs are deleterious from a study population of 12 UVs, present in 59 Dutch families. The p. S1655F, p. R1699W, and p. R1699Q variants in BRCA1 and the p. Y2660D, p. R2784Q, and p. R3052W variants in BRCA2 are classified as deleterious according to our models. The predictions of the p. L246V variant in BRCA1 and of the p. Y42C, p. E462G, p. R2888C, and p. R3052Q variants in BRCA2 are in agreement with published information of them being neutral. The p. R2784W variant in BRCA2 remains uncertain. Conclusions The present study shows that these developed models are useful to classify UVs in clinical genetic practic

Accelerated high-dose radiotherapy alone or combined with either concomitant or sequential chemotherapy; treatments of choice in patients with Non-Small Cell Lung Cancer

<p>Abstract</p> <p>Background</p> <p>Results of high-dose chemo-radiotherapy (CRT), using the treatment schedules of EORTC study 08972/22973 or radiotherapy (RT) alone were analyzed among all patients (pts) with Non Small Cell Lung Cancer (NSCLC) treated with curative intent in our department from 1995–2004.</p> <p>Material</p> <p>Included are 131 pts with medically inoperable or with irresectable NSCLC (TNM stage I:15 pts, IIB:15 pts, IIIA:57 pts, IIIB:43 pts, X:1 pt).</p> <p>Treatment</p> <p>Group I: Concomitant CRT: 66 Gy/2.75 Gy/24 fractions (fx)/33 days combined with daily administration of cisplatin 6 mg/m²: 56 pts (standard).</p> <p>Group II: Sequential CRT: two courses of a 21-day schedule of chemotherapy (gemcitabin 1250 mg/m²d1, cisplatin 75 mg/m2 d2) followed by 66 Gy/2.75 Gy/24 fx/33 days without daily cisplatin: 26 pts.</p> <p>Group III: RT: 66 Gy/2.75 Gy/24 fx/33 days or 60 Gy/3 Gy/20 fx/26 days: 49 pts.</p> <p>Results</p> <p>The 1, 2, and 5 year actuarial overall survival (OS) were 46%, 24%, and 15%, respectively.</p> <p>At multivariate analysis the only factor with a significantly positive influence on OS was treatment with chemo-radiation (P = 0.024) (1-, 2-, and 5-yr OS 56%, 30% and 22% respectively). The incidence of local recurrence was 36%, the incidence of distant metastases 46%.</p> <p>Late complications grade 3 were seen in 21 pts and grade 4 in 4 patients. One patient had a lethal complication (oesophageal). For 32 patients insufficient data were available to assess late complications.</p> <p>Conclusion</p> <p>In this study we were able to reproduce the results of EORTC trial 08972/22973 in a non-selected patient population outside of the setting of a randomised trial. Radiotherapy (66 Gy/24 fx/33 days) combined with either concomitant daily low dose cisplatin or with two neo-adjuvant courses of gemcitabin and cisplatin are effective treatments for patients with locally advanced Non-Small Cell Lung Cancer. The concomitant schedule is also suitable for elderly people with co-morbidity.</p

Ecological Thresholds in the Savanna Landscape: Developing a Protocol for Monitoring the Change in Composition and Utilisation of Large Trees

BACKGROUND: Acquiring greater understanding of the factors causing changes in vegetation structure -- particularly with the potential to cause regime shifts -- is important in adaptively managed conservation areas. Large trees (> or =5 m in height) play an important ecosystem function, and are associated with a stable ecological state in the African savanna. There is concern that large tree densities are declining in a number of protected areas, including the Kruger National Park, South Africa. In this paper the results of a field study designed to monitor change in a savanna system are presented and discussed. METHODOLOGY/PRINCIPAL FINDINGS: Developing the first phase of a monitoring protocol to measure the change in tree species composition, density and size distribution, whilst also identifying factors driving change. A central issue is the discrete spatial distribution of large trees in the landscape, making point sampling approaches relatively ineffective. Accordingly, fourteen 10 m wide transects were aligned perpendicular to large rivers (3.0-6.6 km in length) and eight transects were located at fixed-point photographic locations (1.0-1.6 km in length). Using accumulation curves, we established that the majority of tree species were sampled within 3 km. Furthermore, the key ecological drivers (e.g. fire, herbivory, drought and disease) which influence large tree use and impact were also recorded within 3 km. CONCLUSIONS/SIGNIFICANCE: The technique presented provides an effective method for monitoring changes in large tree abundance, size distribution and use by the main ecological drivers across the savanna landscape. However, the monitoring of rare tree species would require individual marking approaches due to their low densities and specific habitat requirements. Repeat sampling intervals would vary depending on the factor of concern and proposed management mitigation. Once a monitoring protocol has been identified and evaluated, the next stage is to integrate that protocol into a decision-making system, which highlights potential leading indicators of change. Frequent monitoring would be required to establish the rate and direction of change. This approach may be useful in generating monitoring protocols for other dynamic systems

The Effects of Herbivory by a Mega- and Mesoherbivore on Tree Recruitment in Sand Forest, South Africa

Herbivory by megaherbivores on woody vegetation in general is well documented; however studies focusing on the individual browsing effects of both mega- and mesoherbivore species on recruitment are scarce. We determined these effects for elephant Loxodonta africana and nyala Tragelaphus angasii in the critically endangered Sand Forest, which is restricted to east southern Africa, and is conserved mainly in small reserves with high herbivore densities. Replicated experimental treatments (400 m2) in a single forest patch were used to exclude elephant, or both elephant and nyala. In each treatment, all woody individuals were identified to species and number of stems, diameter and height were recorded. Results of changes after two years are presented. Individual tree and stem densities had increased in absence of nyala and elephant. Seedling recruitment (based on height and diameter) was inhibited by nyala, and by elephant and nyala in combination, thereby preventing recruitment into the sapling stage. Neither nyala or elephant significantly reduced sapling densities. Excluding both elephant and nyala in combination enhanced recruitment of woody species, as seedling densities increased, indicating that forest regeneration is impacted by both mega- and mesoherbivores. The Sand Forest tree community approached an inverse J-shaped curve, with the highest abundance in the smaller size classes. However, the larger characteristic tree species in particular, such as Newtonia hildebrandtii, were missing cohorts in the middle size classes. When setting management goals to conserve habitats of key importance, conservation management plans need to consider the total herbivore assemblage present and the resulting browsing effects on vegetation. Especially in Africa, where the broadest suite of megaherbivores still persists, and which is currently dealing with the ‘elephant problem’, the individual effects of different herbivore species on recruitment and dynamics of forests and woodlands are important issues which need conclusive answers