Pre- and on-treatment lactate dehydrogenase as a prognostic and predictive biomarker in advanced non-small cell lung cancer.

BACKGROUND: The survival outcomes of patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) are variable. This study investigated whether pre- and on-treatment lactate dehydrogenase (LDH) could better prognosticate and select patients for ICI therapy. METHODS: Using data from the POPLAR and OAK trials of atezolizumab versus docetaxel in previously treated advanced NSCLC, the authors assessed the prognostic and predictive value of pretreatment LDH (less than or equal to vs greater than the upper limit of normal). They further examined changes in on-treatment LDH by performing landmark analyses and estimated overall survival (OS) distributions according to the LDH level stratified by the response category (complete response [CR]/partial response [PR] vs stable disease [SD]). They repeated pretreatment analyses in subgroups defined by the programmed death ligand 1 (PD-L1) status. RESULTS: This study included 1327 patients with available pretreatment LDH. Elevated pretreatment LDH was associated with an adverse prognosis regardless of treatment (hazard ratio [HR] for atezolizumab OS, 1.49; P = .0001; HR for docetaxel OS, 1.30; P = .004; P for treatment by LDH interaction = .28). Findings for elevated pretreatment LDH were similar for patients with positive PD-L1 expression treated with atezolizumab. Persistently elevated on-treatment LDH was associated with a 1.3- to 2.8-fold increased risk of death at weeks 6, 12, 18, and 24 regardless of treatment. Elevated LDH at 6 weeks was associated with significantly shorter OS regardless of radiological response (HR for CR/PR, 2.10; P = .04; HR for SD, 1.50; P < .01), with similar findings observed at 12 weeks. CONCLUSIONS: In previously treated advanced NSCLC, elevated pretreatment LDH is an independent adverse prognostic marker. There is no evidence that pretreatment LDH predicts ICI benefit. Persistently elevated on-treatment LDH is associated with worse OS despite radiologic response.

Polygenic risk of paclitaxel-induced peripheral neuropathy: a genome-wide association study.

BACKGROUND: Genetic risk factors for chemotherapy-induced peripheral neuropathy (CIPN), a major dose-limiting side-effect of paclitaxel, are not well understood. METHODS: We performed a genome-wide association study (GWAS) in 183 paclitaxel-treated patients to identify genetic loci associated with CIPN assessed via comprehensive neuropathy phenotyping tools (patient-reported, clinical and neurological grading scales). Bioinformatic analyses including pathway enrichment and polygenic risk score analysis were used to identify mechanistic pathways of interest. RESULTS: In total, 77% of the cohort were classified with CIPN (n = 139), with moderate/severe neuropathy in 36%. GWAS was undertaken separately for the three measures of CIPN. GWAS of patient-reported CIPN identified 4 chromosomal regions that exceeded genome-wide significance (rs9846958, chromosome 3; rs117158921, chromosome 18; rs4560447, chromosome 4; rs200091415, chromosome 10). rs4560447 is located within a protein-coding gene, LIMCH1, associated with actin and neural development and expressed in the dorsal root ganglia (DRG). There were additional risk loci that exceeded the statistical threshold for suggestive genome-wide association (P < 1 × 10-5) for all measures. A polygenic risk score calculated from the top 46 ranked SNPs was highly correlated with patient-reported CIPN (r2 = 0.53; P = 1.54 × 10-35). Overlap analysis was performed to identify 3338 genes which were in common between the patient-reported CIPN, neurological grading scale and clinical grading scale GWAS. The common gene set was subsequently analysed for enrichment of gene ontology (GO) and Reactome pathways, identifying a number of pathways, including the axon development pathway (GO:0061564; P = 1.78 × 10-6) and neuronal system (R-HSA-112316; adjusted P = 3.33 × 10-7). CONCLUSIONS: Our findings highlight the potential role of axon development and regeneration pathways in paclitaxel-induced CIPN.

PD-L1 expression as a prognostic marker in patients treated with chemotherapy for metastatic non-small-cell lung cancer.

Background: In metastatic non-small-cell lung cancer (mNSCLC), PD-L1 expression is associated with benefit from immune checkpoint inhibitor (ICI) therapy. However, the significance of PD-L1 expression in chemotherapy-treated patients is uncertain. Methods: Using the chemotherapy control arm of first-line randomized trials, a meta-analysis of the association between efficacy outcomes and PD-L1 status was performed, stratified by assay due to inter-assay differences. Results: Across 12 trials and 4378 patients, overall survival (OS) was superior in high PD-L1 versus negative tumors and low versus negative according to 22C3/28-8 assays. When classified by SP142 assay, no significant difference in response or survival was seen between PD-L1 groups. Conclusion: In mNSCLC, high PD-L1-expressing tumors are associated with longer OS and improved objective rate when treated with chemotherapy. Inter-assay variability impacts outcome results.

Biomarkers are naturally occurring cancer traits that can predict certain events. PD-L1 expression is a biomarker used in advanced lung cancer to predict benefit from immunotherapy. However, the association between PD-L1expression and chemotherapy is unclear. The authors analyzed data from 14 large clinical trials and found that PD-L1 expression could also be used to define a type of lung cancer that responds better to chemotherapy.

Dose modification for haematological toxicity: a survey of Australian medical oncologists.

BACKGROUND: Evidence supporting dose modifications to reduce serious treatment-related adverse events of antineoplastic therapy is limited and frequently based on clinical trial protocols, which are not always generalisable to community patients. eviQ is an online resource with treatment protocols and recommendations for dose modification formulated by expert opinion and evidence-based review. Original recommended haematological thresholds to delay treatment were: neutrophil count <1.5 × 109 /L and platelet count <100 × 109 /L. AIMS: To evaluate the current practices of Australian medical oncologists with regard to haematological dose modifications for antineoplastic treatments, and to determine rates of adherence to eviQ recommendations. METHODS: An online survey regarding haematological dose modifications was distributed to over 400 Medical Oncology Group of Australia members and eviQ medical oncology reference committee members via email. Responses were collated on 18 December 2017. RESULTS: Of 153 respondents, 67% indicated that they did not follow the eviQ haematological dose modification guidelines; 8% delayed curative intent treatment at neutrophil counts <1.5 × 109 /L, compared with 36% for palliative treatment; most delayed treatment at neutrophil counts <1.0 × 109 /L (94% curative and 97% palliative respectively). 70% of clinicians delayed palliative treatment at platelet counts <100 × 109 /L, compared to 34% with curative treatment. No respondents indicated the original haematological cut-off levels were too aggressive. CONCLUSION: The majority of responding medical oncologists indicated that they did not follow the eviQ haematological dose modification guidelines, which were viewed as too conservative. Subsequent to this survey, eviQ reviewed and updated haematological dose modification recommendations.

Balance Deficits and Functional Disability in Cancer Survivors Exposed to Neurotoxic Cancer Treatments.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) persists after treatment in up to 40% of cancer survivors and has been linked with increased balance deficits, disabilities, and fall occurrences. This study aimed to comprehensively assess the links between CIPN, balance deficits, and functional disability and to inform the development of clinical screening tools for patients at risk of these events. PATIENTS AND METHODS: A total of 190 cancer survivors exposed to neurotoxic chemotherapies (age, 57 ± 13 years; average time from completion of neurotoxic therapy, 12 ± 11 months) attended a neurology research clinic for a single cross-sectional assessment of patient-reported and objective CIPN, standing balance in 4 conditions of increasing difficulty, and functional disability. RESULTS: Most patients (68%) reported CIPN symptoms at assessment. Symptomatic patients displayed increased functional disability (F=39.4; P<.001) and balance deficits (F=34.5; P<.001), with degree of balance impairments consistent with a healthy elderly population (age ≥65 years) reporting multiple falls over the subsequent year. Increasing CIPN severity correlated with increasing functional disability (clinically assessed R2=0.46; patient-reported R2=0.49; P<.001) and balance deficits (clinically assessed R2=0.41; patient-reported R2=0.30; P<.001). A 5-factor model of key independent correlates-patient-reported numbness/tingling, weakness, and balance deficit; age; and vibration perception-was strongly linked to balance deficits (R2=0.46; P<.001) and functional disability (R2=0.56; P<.001). CONCLUSIONS: This study confirms links between increasing CIPN severity and increasing balance deficits and functional disability using comprehensive CIPN assessment methodology. The extent of balance deficits in patients with CIPN underscores the functional consequences of neurotoxicity. A 5-factor model provides a foundation for clinical screening tools to assess balance deficits and functional disability in patients exposed to neurotoxic chemotherapies.

Predictive value of PD-L1 and other clinical factors for chemoimmunotherapy in advanced non-small-cell lung cancer.

We investigate if PD-L1 expression and other clinical characteristics predict chemoimmunotherapy (CIT) benefits versus chemotherapy in advanced non-small-cell lung cancer. We performed a meta-analysis of randomized controlled trials of CIT versus chemotherapy identified through electronic searches. In seven randomized controlled trials (n = 4170), CIT prolonged progression-free survival over chemotherapy (hazard ratio [HR]: 0.62; 95% CI: 0.58-0.67; p < 0.00001). The treatment benefits differed between PD-L1-high (HR: 0.41; 95% CI: 0.34-0.49) and PD-L1 low (HR: 0.63; 95% CI: 0.55-0.72; interaction-p = 0.00002) and PD-L1-high and PD-L1-negative (HR: 0.72; 95% CI: 0.65-0.80; interaction-p < 0.00001). Similar benefits were observed regardless of gender, EGFR/ALK status and histological subtype. PD-L1 status is predictive of CIT benefit and may assist patient selection and design of future trials.

Emergency department presentations in early stage breast cancer patients receiving adjuvant and neoadjuvant chemotherapy.

(Neo)adjuvant chemotherapy for early stage breast cancer is associated with side-effects, resulting in increased emergency department (ED) presentations. Treatment-related toxicity can affect quality of life, compromise chemotherapy delivery and treatment outcomes, and increase healthcare use. We performed a retrospective study of ED presentations in patients receiving curative chemotherapy for early breast cancer to identify factors contributing to ED presentations. Of 102 patients, 39 (38%) presented to ED within 30 days of chemotherapy, resulting in 63 ED presentations in total. Most common reasons were non-neutropenic fever (17 presentations/27%), neutropenic fever (15/24%), pain (9/14%), drug reaction (6/10%) and infection (4/6%). Factors significantly associated with ED presentation were adjuvant chemotherapy timing compared to neoadjuvant timing (P = 0.031), prophylactic antibiotics (P = 0.045) and docetaxel-containing regimen (P = 0.018).

Alectinib is effective, safe and tolerable in an adolescent with stage IVB ALK-rearranged adenocarcinoma of the lung.

Anaplastic lymphoma kinase (ALK) inhibitors such as crizotinib and alectinib have been shown to have significant activity in ALK-rearranged non-small cell lung cancers (NSCLC). There are no data for alectinib's safety or efficacy in younger patients, though it is superior to crizotinib in adult trials. We present a 14-year old girl diagnosed with stage IV-B ALK-positive adenocarcinoma of the lung after presenting with cough and fever. She was commenced on alectinib at adult dose and has had sustained complete metabolic remission for 9 months. She is the youngest patient with lung adenocarcinoma to be treated with alectinib.

Optimal clinical assessment strategies for chemotherapy-induced peripheral neuropathy (CIPN): a systematic review and Delphi survey.

BACKGROUND/PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a prominent side effect of the treatment of cancer. Despite this frequent complication, there has been no comprehensive review and quality appraisal of CIPN assessments. The purpose of this study is to provide a definitive quality appraisal of CIPN assessment strategies for clinical use. METHODS: Relevant studies were identified through database searches of Medline, Embase, CINAHL, and Cochrane. CIPN assessment strategies from included articles were extracted and initially rated by an oncologist and neurophysiologist according to criteria related to assessment depth, comprehensiveness, appropriateness, and reliability. The six highest scoring assessment strategies were the focus of a two-round Delphi survey of a working party of 32 physicians, nurses, and consumers to achieve consensus on the highest rated assessments for each criterion. RESULTS: The database search yielded 117 distinct CIPN assessments that were extracted from 2373 articles. Three patient-reported outcome surveys and three clinician-based assessments were included in the Delphi survey. No consensus was generated regarding the best overall CIPN assessment, although good (≥70%) consensus was achieved regarding the best assessment within each criterion. The Participant Neurotoxicity Questionnaire (PNQ) was rated the highest overall and patient-reported outcome (PRO) assessment, while the Total Neuropathy Score clinical version (TNSc) was the highest rated clinician-based assessment. CONCLUSIONS: A diverse range of CIPN assessments currently exists. While several assessments assess CIPN symptoms with adequate comprehensiveness, depth, language, and feasibility, the consensus 'gold standard' clinical assessment remains to be established.

Paclitaxel-induced neuropathy: potential association of MAPT and GSK3B genotypes.

BACKGROUND: Paclitaxel treatment produces dose-limiting peripheral neurotoxicity, which adversely affects treatment and long-term outcomes. In the present study, the contribution of genetic polymorphisms to paclitaxel-induced neurotoxicity were assessed in 21 patients, focusing on polymorphisms involved in the tau-microtubule pathway, an important target of paclitaxel involved in neurotoxicity development. METHODS: Polymorphisms in the microtubule-associated protein tau (MAPT) gene (haplotype 1 and rs242557 polymorphism) and the glycogen synthase kinase-3ß (GSK3ß) gene (rs6438552 polymorphism) were investigated. Neurotoxicity was assessed using neuropathy grading scales, neurophysiological studies and patient questionnaires. RESULTS: A significant relationship between the GSK-3B rs6438552 polymorphism and paclitaxel-induced neurotoxicity was evident. CONCLUSIONS: Polymorphisms in tau-associated genes may contribute to the development of paclitaxel-induced neurotoxicity, although larger series will be necessary to confirm these findings.

Genetic associations between human-directed behavior and intraspecific social aggression in growing pigs.

This study estimated the genetic parameters for human-directed behavior and intraspecific social aggression traits in growing pigs, and explored the phenotypic correlations among them. Data on 2,413 growing pigs were available. Pigs were mixed into new social groups of 18 animals, at 69 ± 5.2 d of age and skin lesions (SL) were counted 24 h (SL24h) post-mixing. Individual behavioral responses to isolation in a weighing crate (CRATE) or when alone in an arena while a human directly approached them (IHAT) were assessed within 48 h post-mixing. Additionally, pigs were tested for behavioral responses to the presence of a single human observer walking in their home pen in a circular motion (WTP) within one (T1) and 4 wk post-mixing (T2) noting pigs that followed, nosed or bit the observer. Animal models were used to estimate genetic and phenotypic parameters for all studied traits. Heritabilities (h2) for SL, CRATE and IHAT responses were low to moderate (0.07 to 0.29), with the highest h2 estimated for speed of moving away from the approaching observer. Low but significant h2 were estimated for nosing (0.09) and biting (0.11) the observer at T2. Positive high genetic correlations (rg) were observed between CRATE and IHAT responses (0.52 to 0.93), and within SL traits (0.79 to 0.91) while positive low to high correlations between the estimated breeding values (rEBV) were estimated within the WTP test (0.24 to 0.59) traits. Positive moderate rg were observed between CRATE and central and posterior SL24h. The rEBV of CRATE and IHAT test responses and WTP test traits were low, mostly negative (-0.21 to 0.05) and not significant. Low positive rEBV (0.06 to 0.24) were observed between SL and the WTP test traits. Phenotypic correlations between CRATE and IHAT responses and SL or WTP test traits were mostly low and not significant. Under the conditions of this study, h2 estimates for all studied traits suggest they could be suitable as a method of phenotyping aggression and fear/boldness for genetic selection purposes. Additionally, genetic correlations between aggression and fear indicators were observed. These findings suggest selection to reduce the accumulation of lesions is likely to make pigs more relaxed in a crate environment, but to alter the engagement with humans in other contexts that depends on the location of the lesions under selection.

We estimated genetic and phenotypic correlations and heritabilities for temperament indicators in growing pigs such as fearfulness (i.e., vocal and physical withdrawal response to an approaching human while isolated in an arena; attempts to escape from a weigh crate); boldness (i.e., biting, following or nosing a human walking inside their home pen) and aggression (i.e., skin lesions). Our results indicate that the studied traits were heritable, and some of these traits could potentially be useful for genetic selection. Additionally, genetic correlations were observed between aggression and fear indicators; pigs with a higher count of skin lesions on their flanks, backs, hind quarters and rear legs 24 h post-mixing (i.e., likely subordinate pigs) tended to display more distress while in isolation in a weigh crate, and were less likely to willingly approach a human. The three boldness indicators were associated, indicating that pigs biting the observer were also those that followed and nosed the observer, suggesting a general increase in exploratory drive and/or a reduction in fearfulness in these animals. These findings suggest that selection to reduce lesions to the rear of the body could have a desirable impact on other important behavioral indicators.

The effect of the proportion of Modern European ancestry on grower and sow performance of pigs in smallholder systems in Uganda.

Several factors, including breed, lead to divergent performance of pigs for production and reproduction traits in different environments. A recent genomics study showed that Modern European (ME) pig breeds contribute to the ancestry of smallholder pigs in the Hoima and Kamuli districts, Uganda. These pigs were also involved in a longitudinal study with several traits recorded, including 540 body weights (WT) of 374 growing pigs, 195 records of total number of piglets born alive (TBA) of 157 sows, and 110 total number weaned (TNW) records of 94 sows. Linear mixed-effects models were used to test for the significance of environmental effects, including housing system, geographic location, and the season when the events occurred as well as animal-specific effects like age, sex, parity, and farrow-to-weaning interval. Stepwise model reduction starting from models with all main effects and pairwise interactions was applied. The final models were then expanded to include proportions of Modern European (ME) ancestry for the subset of animals genotyped, following genomic ancestry analysis based on a Porcine 50K SNP Chip. ME ancestry proportions ranged from 0.02 to 0.50 and were categorized into three classes (low/medium/high ME) based on 33.3% quantiles. The effects of ME classes on WT and TBA were not significant. ME showed a significant effect on TNW. Sows with a high proportion of ME weaned 2.4 piglets more than the low group, the medium ME group being intermediate. This study used genomic data to investigate the effects of genetic ancestry on the performance of smallholder pigs in Uganda. The proportion of Modern European ancestry did not exceed 0.50, therefore not allowing for the comparison of local versus pure "exotic" types of pigs. For the range of ancestries observed, which is the relevant one for current smallholder systems in Uganda, differences were small for the body weight of growing pigs and the number of piglets born alive, while higher proportions of ME ancestry resulted in significantly more piglets weaned. The availability of genotypes of a higher number of growing pigs would have been beneficial for drawing conclusions on the effect of ME ancestry on the growth rates of smallholder pigs in Uganda.

Physical activity behaviors in cancer survivors treated with neurotoxic chemotherapy.

AIM: There are many barriers to physical activity among cancer survivors. Survivors treated with neurotoxic chemotherapy may develop chemotherapy-induced peripheral neuropathy (CIPN) and experience additional barriers related to sensorimotor and mobility deficits. This study examined physical activity behaviors, including physical activity predictors, among cancer survivors treated with neurotoxic chemotherapies. METHODS: A cross-sectional study of 252 participants, 3-24 months after neurotoxic chemotherapy, was undertaken. Physical activity was self-reported (IPAQ). CIPN was self-reported (FACT/GOG-Ntx-13), clinically graded (NCI-CTCAE), and objectively measured using neurological grading scales and neurophysiological techniques (tibial and sural nerve conduction studies). Balance (Swaymeter) and fine motor skills (grooved pegboard) were assessed. Regression models were used to identify clinical, demographic and CIPN predictors of walking and moderate-vigorous physical activity. RESULTS: Forty-four percent of participants did not meet recommended physical activity guidelines (≥150 min/week). Sixty-six percent presented with CIPN. Nineteen percent of participants with CIPN reported that symptoms interfered with their ability to be physically active. A lower proportion of survivors aged ≥60, with grade ≥1 CIPN or BMI ≥30, reported meeting physical activity guidelines (all p < .05). Regression models identified older age, higher BMI, and patient-reported CIPN associated with lower walking, while higher BMI and females were associated with lower moderate-vigorous physical activity. Neurologically assessed CIPN did not associate with walking or moderate-vigorous physical activity. CONCLUSION: Cancer survivors exposed to neurotoxic chemotherapy have low physical activity levels. Further work should examine the factors causing physical activity limitations in this cohort and designing interventions to improve physical function and quality of life in survivors.

Genetic Associations of Novel Behaviour Traits Derived from Social Network Analysis with Growth, Feed Efficiency, and Carcass Characteristics in Pigs.

Reducing harmful aggressive behaviour remains a major challenge in pig production. Social network analysis (SNA) showed the potential in providing novel behavioural traits that describe the direct and indirect role of individual pigs in pen-level aggression. Our objectives were to (1) estimate the genetic parameters of these SNA traits, and (2) quantify the genetic associations between the SNA traits and commonly used performance measures: growth, feed intake, feed efficiency, and carcass traits. The animals were video recorded for 24 h post-mixing. The observed fighting behaviour of each animal was used as input for the SNA. A Bayesian approach was performed to estimate the genetic parameters of SNA traits and their association with the performance traits. The heritability estimates for all SNA traits ranged from 0.01 to 0.35. The genetic correlations between SNA and performance traits were non-significant, except for weighted degree with hot carcass weight, and for both betweenness and closeness centrality with test daily gain, final body weight, and hot carcass weight. Our results suggest that SNA traits are amenable for selective breeding. Integrating these traits with other behaviour and performance traits may potentially help in building up future strategies for simultaneously improving welfare and performance in commercial pig farms.

Generalizability of immune checkpoint inhibitor trials to real-world patients with advanced non-small cell lung cancer.

INTRODUCTION: Based on data from randomized controlled trials (RCTs), immune checkpoint inhibitors (ICI) are standard-of-care in advanced non-small cell lung cancer (aNSCLC). However, trial eligibility criteria are restrictive, and participants and outcomes may not represent the wider population. We aim to assess the generalizability of key phase III RCTs to real-world patients. METHODS: Among aNSCLC patients enrolled in the Embedding Research (and Evidence) in Cancer Healthcare (EnRICH) program between 26/6/17-18/2/21, we assessed the proportion of patients who fulfilled key trial eligibility criteria: performance status (PS) 0-1, normal laboratory results, no EGFR/ALK mutations, no exclusionary comorbidities (previous cancer, conditions necessitating steroid use, autoimmune diseases, HIV, hepatitis B/C, tuberculosis, interstitial lung disease, organ transplantation). We defined patients who met all assessed criteria as trial-typical and describe ICI uptake and overall survival (OS). RESULTS: Of 454 patients (median age 71 years, 42.1% female), 30% were trial-typical. Less than half received ICI (47.6%), with trial-typical patients more likely to receive ICI (69.1% vs 38.4%, adjusted odds ratio 3.77, 95% CI 2.40-5.91). Median OS was 10.2 and 5.4 months in patients receiving first- and second-line ICI, respectively. Rationalizing trial criteria to include patients with PS ≤ 2 and exclude those with targetable mutations, steroid use, autoimmune diseases, interstitial lung disease, tuberculosis or organ transplantation increased the proportion of trial-typical patients to 57.3%. CONCLUSIONS: Landmark phase III RCTs in aNSCLC have limited generalizability. OS of real-world patients receiving ICI is shorter than reported in trials. Novel ICI trials should consider broader eligibility criteria to improve their generalizability.

Early, progressive, and sustained dysfunction of sensory axons underlies paclitaxel-induced neuropathy.

Paclitaxel is used in the adjuvant treatment of breast cancer. It induces disabling and potentially long-lasting sensory neuropathy. This study systematically and prospectively investigated sensory function, using clinical grading scales, quantitative sensory testing, and neurophysiological and nerve excitability studies in 28 patients with early-stage breast cancer. After administration of 529 ± 41 mg/m(2) paclitaxel, 71% of patients developed neuropathic symptoms by 6 weeks of treatment. Early and progressive increases in stimulus threshold (P < 0.05) and reduction in sensory amplitudes from 47.0 ± 3.3 µV to 42.4 ± 3.4 µV (P < 0.05) occurred by 4 weeks, with a further reduction by final treatment (33.7 ± 3.0 µV, P < 0.001). The majority of patients (63%) did not experience recovery of neuropathic symptoms at follow-up. Axonal disruption did not relate to membrane conductance dysfunction. We found that paclitaxel produces early sensory dysfunction and leads to persistent neuropathy. Importantly, significant axonal dysfunction within the first month of treatment predated symptom onset, suggesting a window for neuroprotective therapies.

A Mix of Old British and Modern European Breeds: Genomic Prediction of Breed Composition of Smallholder Pigs in Uganda.

Pig herds in Africa comprise genotypes ranging from local ecotypes to commercial breeds. Many animals are composites of these two types and the best levels of crossbreeding for particular production systems are largely unknown. These pigs are managed without structured breeding programs and inbreeding is potentially limiting. The objective of this study was to quantify ancestry contributions and inbreeding levels in a population of smallholder pigs in Uganda. The study was set in the districts of Hoima and Kamuli in Uganda and involved 422 pigs. Pig hair samples were taken from adult and growing pigs in the framework of a longitudinal study investigating productivity and profitability of smallholder pig production. The samples were genotyped using the porcine GeneSeek Genomic Profiler (GGP) 50K SNP Chip. The SNP data was analyzed to infer breed ancestry and autozygosity of the Uganda pigs. The results showed that exotic breeds (modern European and old British) contributed an average of 22.8% with a range of 2-50% while "local" blood contributed 69.2% (36.9-95.2%) to the ancestry of the pigs. Runs of homozygosity (ROH) greater than 2 megabase (Mb) quantified the average genomic inbreeding coefficient of the pigs as 0.043. The scarcity of long ROH indicated low recent inbreeding. We conclude that the genomic background of the pig population in the study is a mix of old British and modern pig ancestries. Best levels of admixture for smallholder pigs are yet to be determined, by linking genotypes and phenotypic records.