Response-based Selection Research Articles

Involved Site Radiotherapy in HPV Positive Oropharyngeal Cancer: Patterns of Failure Analysis Across Prospective De-Escalation Trials

HPV-associated oropharyngeal cancers (HPV+OPC) have a favorable prognosis with ongoing efforts to reduce long term toxicity while maintaining oncologic outcomes. One method under investigation includes lowering the elective radiation dose or in some cases omitting radiation to elective lymphatic nodal stations. Furthermore, pre-clinical evidence demonstrates that elective nodal irradiation blunts the anti-tumor immune response in head and neck cancer. This is a pooled secondary analysis reporting patterns of failure in patients (pts) with HPV+OPC enrolled on consecutive induction chemo- or chemoimmunotherapy (IC) based response-adaptive de-escalation trials and treated with involved-site radiotherapy (ISRT). Pts treated on two prospective phase II trials as well as on a prospective cohort registry were included for analysis. Pts with ≥ 50% response to IC based on RECIST 1.1 who received de-escalated definitive radiotherapy (RT) or concurrent chemoradiation (CRT) with ISRT were evaluable. Pts with locally advanced low risk or high-risk HPV+OPC (LR and HR, respectively) were eligible for enrollment. Pts were considered to have HR if at least one of the following criteria was met: T4 primary, N2c-N3 disease (AJCC 7th ed.), or > 10-20 pack years smoking. In the first trial, pts with ≥ 50% response to IC received RT to gross disease plus a 1.5 cm margin (PTV1) and to the next echelon of uninvolved nodes (PTV2). Pts with LR received 50 Gy in 2 Gy daily fractions without chemotherapy; pts with HR received 30 Gy in 1.5 Gy BID fractions to PTV2 with a 15 Gy sequential boost to PTV1 with CRT. In the subsequent trial, pts with ≥ 50% response received RT to PTV1 alone to 50 Gy in 2 Gy daily fractions; concurrent CRT was included if pts had HR. Survival was estimated using the Kaplan Meier method for progression free survival (PFS), locoregional PFS (LRPFS), and overall survival (OS). Patterns of failure analysis was performed by comparing RT plans to radiographic surveillance scans. Of 172 evaluable pts, 119 (69.2%) achieved a ≥ 50% response to IC and received definitive ISRT. 45 (37.8%) pts evaluated received RT to gross disease only plus margin without the next nodal echelon included. With a median follow up of 46 (IQR 34-65) months, 3-year PFS, LRPFS, and OS with their 95% confidence intervals were 96.2% (90.1-98.5%), 97.1% (91.1-99.0%), and 96.2% (90.3-98.6%), respectively. All locoregional failures were in-field and in the high dose region. No failures were observed in the RT omitted neck. This prospective experience demonstrates feasible volume de-escalation using IC response-based selection with progressively smaller elective volumes over time. Notably, despite a marked reduction in elective treatment volume, there were no regional out-of-field failures. IC may allow for selection of pts with favorable tumor biology and microscopic disease sterilization in the regional nodes. Further efforts at elective nodal de-escalation are needed.

Growth Performance, Lipid Deposition and Serum Biochemistry in Golden Pompano Trachinotus Ovatus (Linnaeus, 1758) Fed Diets with Various Fish Oil Substitutes

In this study, 640 golden pompano (mean initial weight of 82.85±2.36 g) were randomly allocated into 32 floating net cages. Eight experimental diets involving various lipid sources were given. They were: fish oil (FO), krill oil (KO), soybean oil (SO), corn oil (CO), 1:1 FO-SO, 1:1 FO-CO, 1:1 KO-SO and 1:1 KO-CO. The results showed that the specific growth rate in the SO, CO, 1:1 FO-SO and 1:1 KO-SO groups was significantly lower than in the FO group (P<0.05), and the 1:1 KO-CO had lower feed conversion ratio (FCR) among all the diets. The muscle fatty acid compositions were closely correlated with the fatty acid composition of the diets. Moreover, the serum MDA content of golden pompano fed the other seven diets was significantly lower than that of the fish fed the FO diet (P<0.05) except for the 1:1KO-CO diet, with the lowest MDA content, which occurred in KO diet. Accordingly, we concluded that the FO, KO, 1:1 FO-SO and 1:1 KO-CO diets resulted in improvements in growth performance in golden pompano. Moreover, KO diet regulated some physiological and biochemical indicators. This study could provide a basis for the response-based selection of optimal lipid sources.

The rat retrosplenial cortex as a link for frontal functions: A lesion analysis

Cohorts of rats with excitotoxic retrosplenial cortex lesions were tested on four behavioural tasks sensitive to dysfunctions in prelimbic cortex, anterior cingulate cortex, or both. In this way the study tested whether retrosplenial cortex has nonspatial functions that reflect its anatomical interactions with these frontal cortical areas. In Experiment 1, retrosplenial cortex lesions had no apparent effect on a set-shifting digging task that taxed intradimensional and extradimensional attention, as well as reversal learning. Likewise, retrosplenial cortex lesions did not impair a strategy shift task in an automated chamber, which involved switching from visual-based to response-based discriminations and, again, included a reversal (Experiment 2). Indeed, there was evidence that the retrosplenial lesions aided the initial switch to response-based selection. No lesion deficit was found on an automated cost-benefit task that pitted size of reward against effort to achieve that reward (Experiment 3). Finally, while retrosplenial cortex lesions affected matching-to-place task in a T-maze, the profile of deficits differed from that associated with prelimbic cortex damage (Experiment 4). When the task was switched to a nonmatching design, retrosplenial cortex lesions had no apparent effect on performance. The results from the four experiments show that many frontal tasks do not require the retrosplenial cortex, highlighting the specificity of their functional interactions. The results show how retrosplenial cortex lesions spare those learning tasks in which there is no mismatch between the internal and external representations used to guide behavioural choice. In addition, these experiments further highlight the importance of the retrosplenial cortex in solving tasks with a spatial component.

Response-based selection of barley cultivars and legume species for complementarity: Root morphology and exudation in relation to nutrient source

Phosphorus (P) and nitrogen (N) use efficiency may be improved through increased biodiversity in agroecosystems. Phenotypic variation in plants’ response to nutrient deficiency may influence positive complementarity in intercropping systems. A multicomponent screening approach was used to assess the influence of P supply and N source on the phenotypic plasticity of nutrient foraging traits in barley (H. vulgare L.) and legume species. Root morphology and exudation were determined in six plant nutrient treatments. A clear divergence in the response of barley and legumes to the nutrient treatments was observed. Root morphology varied most among legumes, whereas exudate citrate and phytase activity were most variable in barley. Changes in root morphology were minimized in plants provided with ammonium in comparison to nitrate but increased under P deficiency. Exudate phytase activity and pH varied with legume species, whereas citrate efflux, specific root length, and root diameter lengths were more variable among barley cultivars. Three legume species and four barley cultivars were identified as the most responsive to P deficiency and the most contrasting of the cultivars and species tested. Phenotypic response to nutrient availability may be a promising approach for the selection of plant combinations for minimal input cropping systems.

Advanced Colorectal Liver Metastases and Surgery After Preoperative Chemotherapy: Is Response-Based Selection Enough?

Advanced Colorectal Liver Metastases and Surgery After Preoperative Chemotherapy: Is Response-Based Selection Enough?

High Survival Rate After Two-Stage Resection of Advanced Colorectal Liver Metastases: Response-Based Selection and Complete Resection Define Outcome

Prolonged survival after two-stage resection (TSR) of advanced colorectal liver metastases (CLM) may be the result of selection of best responders to chemotherapy. The impact of complete resection in this well-selected group is controversial. Data on 890 patients undergoing resection and 879 patients who received only chemotherapy for CLM were collected prospectively. We used intent-to-treat analysis to evaluate the survival of patients who underwent TSR. Additionally, we evaluated a cohort of nonsurgically treated patients selected to mirror the TSR population: colorectal metastases with liver-only disease, objective response to chemotherapy, and alive 1 year after chemotherapy initiation. Sixty-five patients underwent the first stage of TSR; 62 patients fulfilled the inclusion criteria for the medical group. TSR patients had a mean of 6.7 ± 3.4 CLM with mean size of 4.5 ± 3.1 cm. Nonsurgical patients had a mean of 5.9 ± 2.9 CLM with mean size of 5.4 ± 3.4 cm (not significant). Forty-seven TSR patients (72%) completed the second stage. Progression between stages was the main cause of noncompletion of the second stage (61%). After 50 months median follow-up, the 5-year survival rate was 51% in the TSR group and 15% in the medical group (P = .005). In patients who underwent TSR, noncompletion of TSR and major postoperative complications were independently associated with worse survival. TSR is associated with excellent outcome in patients with advanced CLM as a result of both selection by chemotherapy and complete resection of metastatic disease.

Immune response to Newcastle disease virus in chicken lines divergently selected for cutaneous hypersensitivity

This paper describes for the first time the differential immune response to virulent Newcastle disease virus (NDV) in birds differing in cell-mediated immunity, as measured by response to phytohaemagglutinin-P. To explore potential host-pathogen interactions, peripheral blood mononuclear cells (PBMC) were collected from 40 extreme responder birds (20 birds each from high and low cell-mediated immunity lines). PBMC cultures were stimulated by virulent NDV and temporal expression profiles of interferon-gamma (IFN-gamma), and inducible nitric oxide synthase (iNOS) mRNA was evaluated by semiquantitative reverse transcription polymerase chain reaction (PCR). To further explore the correlation of iNOS mRNA expression and nitric oxide (NO) production, we assayed the culture supernatants for NO. NO production, as well as iNOS and IFN-gamma mRNA expression, was significantly (P < 0.05) higher in the line with higher cell-mediated immunity. In our study, a significant (P < 0.05) difference was observed between the lines for IFN-gamma promoter polymorphism for the TspEI site. The high cell-mediated immunity line mostly revealed the genotype (GG) with a 168-bp fragment. On the other hand, this genotype was not predominant in the low cell-mediated immunity line. Later, quantitative real-time PCR demonstrated higher (P < 0.01) IFN-gamma mRNA transcription in the genotype GG in response to NDV. This difference in promoter region may be responsible for differential IFN-gamma mRNA transcription in chicken lines. Furthermore, birds of high cell-mediated immunity line showed better adaptive immunity to booster NDV vaccination as revealed by an enhanced antibody titre. Thus, this study provides baseline data on the effect of phytohaemagglutinin-P response-based selection on immune responses to virulent NDV and the data could be of immense importance to poultry geneticist and immunologist attempting to breed poultry for disease resistance.

Temporal dynamics of parietal cortex involvement in visual search

The functional–neuroanatomic relationship that describes the involvement of the parietal cortex in visual search was investigated using repetitive transcranial magnetic stimulation (rTMS; 10 Hz, 500 ms in duration). Twelve adult participants performed feature-based visual search for a unique letter—without eye movements—under conditions that involved manipulations of search efficiency (efficient versus inefficient) and target-selection demands (set-size: 4 versus 10). rTMS was applied over the right posterior parietal cortex at the onset of the search array for all factorial conditions (0–500 ms); stimulation was additionally administered at 500 ms post-array onset (500–1000 ms) during inefficient search (set-size 10). Stimulation over the primary sensorimotor cortex served as a within-subjects control condition, and eye movements were monitored continuously. Significant increases in reaction time were restricted to parietal stimulation during inefficient search (set-size 10), with interference observed when rTMS was administered at the onset of the search array and at 500 ms post-array onset. The early effect was confined to target-present trials and the late effect was confined to target-absent trials, which may indicate temporally dissociable parietal involvement in target detection and response-based selection and/or search termination, respectively. Error rates did not vary significantly as a function of any of the independent variables. Taken together, these results are consistent with evidence from functional magnetic resonance studies indicating that inefficient feature-based visual search requires an intact parietal cortex, and also indicate that the parietal cortex is involved in inefficient search later than has been previously reported.