Deletion of the inhibitory co-receptor CTLA-4 enhances and invigorates chimeric antigen receptor T cells.

Chimeric antigen receptor (CAR) T cell therapy targeting CD19 has achieved tremendous success treating B cell malignancies; however, some patients fail to respond due to poor autologous T cell fitness. To improve response rates, we investigated whether disruption of the co-inhibitory receptors CTLA4 or PD-1 could restore CART function. CRISPR-Cas9-mediated deletion of CTLA4 in preclinical models of leukemia and myeloma improved CAR T cell proliferation and anti-tumor efficacy. Importantly, this effect was specific to CTLA4 and not seen upon deletion of CTLA4 and/or PDCD1 in CAR T cells. Mechanistically, CTLA4 deficiency permitted unopposed CD28 signaling and maintenance of CAR expression on the T cell surface under conditions of high antigen load. In clinical studies, deletion of CTLA4 rescued the function of T cells from patients with leukemia that previously failed CAR T cell treatment. Thus, selective deletion of CTLA4 reinvigorates dysfunctional chronic lymphocytic leukemia (CLL) patient T cells, providing a strategy for increasing patient responses to CAR T cell therapy.

Proton Beam Therapy in the Reirradiation Setting of Brain and Base of Skull Tumour Recurrences.

The therapeutic management of local tumour recurrence after a first course of radical radiotherapy is always complex. Surgery and reirradiation carry increased morbidity due to radiation-induced tissue changes. Proton beam therapy (PBT) might be advantageous in the reirradiation setting, thanks to its distinct physical characteristics. Here we systematically reviewed the use of PBT in the management of recurrent central nervous system (CNS) and base of skull (BoS) tumours, as published in the literature. The research question was framed following the Population, Intervention, Comparison and Outcomes (PICO) criteria: the population of the study was cancer patients with local disease recurrence in the CNS or BoS; the intervention was radiation treatment with PBT; the outcomes of the study focused on the clinical outcomes of PBT in the reirradiation setting of local tumour recurrences of the CNS or BoS. The identification stage resulted in 222 records in Embase and 79 in Medline as of March 2023. Sixty-eight duplicates were excluded at this stage and 56 were excluded after screening as not relevant, not in English or not full-text articles. Twelve full-text articles were included in the review and are presented according to the site of disease, namely BoS, brain or both brain and BoS. This review showed that reirradiation of brain/BoS tumour recurrences with PBT can provide good local control with acceptable toxicity rates. However, reirradiation of tumour recurrences in the CNS or BoS setting needs to consider several factors that can increase the risk of toxicities. Therefore, patient selection is crucial. Randomised evidence is needed to select the best radiation modality in this group of patients.

Assessing Equity of Access to Proton Beam Therapy: A Literature Review.

Proton beam therapy (PBT) is one of the most advanced radiotherapy technologies, with growing evidence to support its use in specific clinical scenarios and exponential growth of demand and capacity worldwide over the past few decades. However, geographical inequalities persist in the distribution of PBT centres, which translate into variations in access and use of this technology. The aim of this work was to look at the factors that contribute to these inequalities, to help raise awareness among stakeholders, governments and policy makers. A literature search was conducted using the Population, Intervention, Comparison, Outcomes (PICO) criteria. The same search strategy was run in Embase and Medline and identified 242 records, which were screened for manual review. Of these, 24 were deemed relevant and were included in this analysis. Most of the 24 publications included in this review originated from the USA (22/24) and involved paediatric patients, teenagers and young adults (61% for children and/or teenagers and young adults versus 39% for adults). The most reported indicator of disparity was socioeconomic status (16/24), followed by geographical location (13/24). All the studies evaluated in this review showed disparities in the access to PBT. As paediatric patients make up a significant proportion of the PBT-eligible patients, equity of access to PBT also raises ethical considerations. Therefore, further research is needed into the equity of access to PBT to reduce the care gap.

Outcomes of Patients Treated in the UK Proton Overseas Programme: Central Nervous System Group.

AIMS: In 2008, the UK National Health Service started the Proton Overseas Programme (POP), to provide access for proton beam therapy (PBT) abroad for selected tumour diagnoses while two national centres were being planned. The clinical outcomes for the patient group treated for central nervous system (CNS), base of skull, spinal and paraspinal malignancies are reported here. MATERIALS AND METHODS: Since the start of the POP, an agreement between the National Health Service and UK referring centres ensured outcomes data collection, including overall survival, local tumour control and late toxicity data. Clinical and treatment-related data were extracted from this national patient database. Grade ≥3 late toxicities were reported following Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 definition, occurring later than 90 days since the completion of treatment. RESULTS: Between 2008 and September 2020, 830 patients were treated within the POP for the above listed malignancies. Overall survival data were available for 815 patients and local control data for 726 patients. Toxicity analysis was carried out on 702 patients, with patients excluded due to short follow-up (<90 days) and/or inadequate toxicity data available. After a median follow-up of 3.34 years (0.06-11.58), the overall survival was 91.2%. The local control rate was 85.9% after a median follow-up of 2.81 years (range 0.04-11.58). The overall grade ≥3 late toxicity incidence was 11.97%, after a median follow-up of 1.72 years (0.04-8.45). The median radiotherapy prescription dose was 54 GyRBE (34.8-79.2). CONCLUSIONS: The results of this study indicate the safety of PBT for CNS tumours. Preliminary clinical outcomes following PBT for paediatric/teen and young adult and adult CNS tumours treated within the POP are encouraging, which reflects accurate patient selection and treatment quality. The rate of late effects compares favourably with published cohorts. Clinical outcomes from this patient cohort will be compared with those of UK-treated patients since the start of the national PBT service in 2018.

Clinico-pathological predictors of clinical complete response in rectal cancer.

PURPOSE: Prediction of clinical complete response in rectal cancer before neoadjuvant chemo-radiotherapy treatment enables treatment selection. Patients predicted to have complete response could have chemo-radiotherapy, and others could have additional doublet chemotherapy at this stage of their treatment to improve their overall outcome. This work investigates the role of clinical variables in predicting clinical complete response. METHOD: Using the UK-based OnCoRe database (2008 to 2019), we performed a propensity-score matched study of 322 patients who received neoadjuvant chemoradiotherapy. We collected pre-treatment clinic-pathological, inflammatory and radiotherapy-related characteristics. We determined the odds for the occurrence of cCR using conditional logistic regression models. We derived the post-model Area under the Curve (AUC) as an indicator of discrimination performance and stated a priori that an AUC of 0.75 or greater was required for potential clinical utility. RESULTS: Pre-treatment tumour diameter, mrT-stage, haemoglobin, alkaline phosphate and total radiotherapy depths were associated with cCR on univariable and multivariable analysis. Additionally, neutrophil to lymphocyte ratio (NLR), neutrophil-monocyte to lymphocyte ratio (NMLR), lymphocyte count and albumin were all significantly associated with cCR on multivariable analysis. A nomogram using the above parameters was developed with a resulting ROC AUC of 0.75. CONCLUSION: We identified routine clinic-pathological, inflammatory and radiotherapy-related variables which are independently associated with cCR. A nomogram was developed to predict cCR. The performance characteristics from this model were on the prior clinical utility threshold. Additional research is required to develop more associated variables to better select patients with rectal cancer undergoing chemoradiotherapy who may benefit from pursuing a W&W strategy.

Normal Tissue Complication Probability Modelling for Toxicity Prediction and Patient Selection in Proton Beam Therapy to the Central Nervous System: A Literature Review.

Normal tissue complication probability (NTCP) models can guide clinical decision making in radiotherapy. In recent years, they have been used for patient selection for proton beam therapy (PBT) for some anatomical tumour sites. This review synthesizes the published evidence regarding the use of NTCP models to predict the toxicity of PBT, for different end points in patients with brain tumours. A search of Medline and Embase using the Patients, Intervention, Comparison, Outcome (PICO) criteria was undertaken. In total, 37 articles were deemed relevant and were reviewed in detail. Nineteen articles on NTCP modelling of toxicity end points were included. Of these, 11 were comparative NTCP studies of PBT versus conventional photon radiotherapy (XRT), which evaluated differences in plan dosimetry and then assumed that XRT-derived literature estimates of NTCP would be applicable to both. Seven papers derived NTCP models based on PBT outcome data, two of which provided model parameters. Among analysed end points, the reduced risk of secondary tumours with PBT as compared with XRT is estimated - through modelling studies - to be considerable and was highlighted by most authors. For other analysed end points, the clinical benefit of PBT mainly depends on tumour location in relation to organs at risk as well as prescription doses. NTCP models can be useful tools for treatment plan comparison. However, most published toxicity data were derived from XRT cohorts; this review has highlighted the need for further studies relating dose-volume parameters to observed toxicity in PBT-treated patients. Specifically, there is a need for PBT-specific NTCP models that can be implemented in the clinical practice. NTCP models built on robust clinical data for the most common radiotherapy toxicities in the brain would potentially redefine the current indications for PBT.

A novel use for routine CBCT imaging during radiotherapy to detect COVID-19.

INTRODUCTION: Thoracic CT is a useful tool in the early diagnosis of patients with COVID-19. Typical appearances include patchy ground glass shadowing. Thoracic radiotherapy uses daily cone beam CT imaging (CBCT) to check for changes in patient positioning and anatomy prior to treatment through a qualitative assessment of lung appearance by radiographers. Observation of changes related to COVID-19 infection during this process may facilitate earlier testing improving patient management and staff protection. METHODS: A tool was developed to create overview reports for all CBCTs for each patient throughout their treatment. Reports contain coronal maximum intensity projection (MIP's) of all CBCTs and plots of lung density over time. A single therapeutic radiographer undertook a blinded off-line audit that reviewed 150 patient datasets for tool optimisation in which medical notes were compared to image findings. This cohort included 75 patients treated during the pandemic and 75 patients treated between 2014 and 2017. The process was repeated retrospectively on a subset of the 285 thoracic radiotherapy patients treated between January-June 2020 to assess the efficiency of the tool and process. RESULTS: Three patients in the n = 150 optimisation cohort had confirmed COVID-19 infections during their radiotherapy. Two of these were detected by the reported image assessment process. The third case was not detected on CBCT due to minimal density changes in the visible part of the lungs. Within the retrospective cohort four patients had confirmed COVID-19 based on RT-PCR tests, three of which were retrospectively detected by the reported process. CONCLUSION: The preliminary results indicate that the presence of COVID-19 can be detected on CBCT by therapeutic radiographers. IMPLICATIONS FOR PRACTICE: This process has now been extended to clinical service with daily assessments of all thoracic CBCTs. Changes noted are referred for oncologist review.

Safe and Ethical Artificial Intelligence in Radiotherapy - Lessons Learned From the Aviation Industry.

Ethical artificial intelligence (AI) frameworks can be the catalyst in improving the safety and wellbeing of people when developing AI systems. In 2020 Rolls-Royce released its ethical and trustworthiness toolkit, The Aletheia FrameworkTM, which helps guide organisations as they consider the ethics around the use of AI. It covers three facets: social impact, accuracy and trust, and governance - which apply across all uses of AI. By adopting AI ethics and trust frameworks, oncologists can ensure the ratio between the benefit and harms of AI can be maximised. With AI transforming every sector, collaboration across industries to share ideas and learn from each other - even unlikely partnerships between engineering and oncology - could help optimise that transition.

An NK-like CAR T cell transition in CAR T cell dysfunction.

Chimeric antigen receptor (CAR) T cell therapy has achieved remarkable success in hematological malignancies but remains ineffective in solid tumors, due in part to CAR T cell exhaustion in the solid tumor microenvironment. To study dysfunction of mesothelin-redirected CAR T cells in pancreatic cancer, we establish a robust model of continuous antigen exposure that recapitulates hallmark features of T cell exhaustion and discover, both in vitro and in CAR T cell patients, that CAR dysregulation is associated with a CD8+ T-to-NK-like T cell transition. Furthermore, we identify a gene signature defining CAR and TCR dysregulation and transcription factors, including SOX4 and ID3 as key regulators of CAR T cell exhaustion. Our findings shed light on the plasticity of human CAR T cells and demonstrate that genetic downmodulation of ID3 and SOX4 expression can improve the efficacy of CAR T cell therapy in solid tumors by preventing or delaying CAR T cell dysfunction.

The Impact of Intra-thoracic Anatomical Changes upon the Delivery of Lung Stereotactic Ablative Radiotherapy.

AIMS: So far, the impact of intra-thoracic anatomical changes (ITACs) on patients treated with stereotactic ablative radiotherapy (SABR) for early-stage non-small cell lung cancer is unknown. Studying these is important, as ITACs have the potential to impact the workflow and reduce treatment quality. The aim of this study was to assess and categorise ITACs, as detected on cone beam computed tomography scans (CBCT), and their subsequent impact upon treatment in lung cancer patients treated with SABR. MATERIALS AND METHODS: CBCTs from 100 patients treated with SABR for early non-small cell lung cancer were retrospectively reviewed. The presence of the following ITACs was assessed: atelectasis, infiltrative change, pleural effusion, baseline shift and gross tumour volume (GTV) increase and decrease. ITACs were graded using a traffic light protocol. This was adapted from a tool previously developed to assesses potential target undercoverage or organ at risk overdose. The frequency of physics or clinician review was noted. A linear mixed effects model was used to assess the relationship between ITAC grade and set-up time (time from first CBCT to beam delivery). RESULTS: ITACs were observed in 22% of patients. Twenty-one per cent of these were categorised as 'red', implying a risk of underdosage to the GTV. Most were 'yellow' (51%), indicating little impact upon planning target volume coverage of the GTV. Physics or clinician review was required in 10% of all treatment fractions overall. Three patients needed their treatment replanned. The mixed effect model analysis showed that ITACs cause a significant prolongation of set-up time (Χ2(3) = 9.22, P = 0.02). CONCLUSION: Most ITACs were minor, but associated with unplanned physics or clinician review, representing a potentially significant resource burden. ITACs also had a significant impact upon set-up time, with consequences for the wider workflow and intra-fraction motion. Detailed guidance on the management of ITACs is needed to provide support for therapeutic radiographers delivering lung SABR.

Impact of the COVID-19 pandemic on tuberculosis management in Spain.

BACKGROUND: The impact of COVID-19 on the diagnosis and management of tuberculosis (TB) patients is unknown. METHODS: Participating centres completed a structured web-based survey regarding changes to TB patient management during the COVID-19 pandemic. The study also included data from participating centres on patients aged ≥18 diagnosed with TB in 2 periods: March 15 to June 30, 2020 and March 15 to June 30, 2019. Clinical variables and information about patient household contacts were retrospectively collected. RESULTS: A total of 7 (70%) TB units reported changes in their usual TB team operations. Across both periods of study, 169 patients were diagnosed with active TB (90 in 2019, 79 in 2020). Patients diagnosed in 2020 showed more frequent bilateral lesions in chest X-ray than patients diagnosed in 2019 (P = 0.004). There was a higher percentage of latent TB infection and active TB among children in households of patients diagnosed in 2020, compared with 2019 (P = 0.001). CONCLUSIONS: The COVID-19 pandemic has caused substantial changes in TB care. TB patients diagnosed during the COVID-19 pandemic showed more extended pulmonary forms. The increase in latent TB infection and active TB in children of patient households could reflect increased household transmission due to anti-COVID-19 measures.

Evaluation of Ultra-low-dose Paediatric Cone-beam Computed Tomography for Image-guided Radiotherapy.

AIMS: In image-guided radiotherapy, daily cone-beam computed tomography (CBCT) is rarely applied to children due to concerns over imaging dose. Simulating low-dose CBCT can aid clinical protocol design by allowing visualisation of new scan protocols in patients without delivering additional dose. This work simulated ultra-low-dose CBCT and evaluated its use for paediatric image-guided radiotherapy by assessment of image registration accuracy and visual image quality. MATERIALS AND METHODS: Ultra-low-dose CBCT was simulated by adding the appropriate amount of noise to projection images prior to reconstruction. This simulation was validated in phantoms before application to paediatric patient data. Scans from 20 patients acquired at our current clinical protocol (0.8 mGy) were simulated for a range of ultra-low doses (0.5, 0.4, 0.2 and 0.125 mGy) creating 100 scans in total. Automatic registration accuracy was assessed in all 100 scans. Inter-observer registration variation was next assessed for a subset of 40 scans (five scans at each simulated dose and 20 scans at the current clinical protocol). This subset was assessed for visual image quality by Likert scale grading of registration performance and visibility of target coverage, organs at risk, soft-tissue structures and bony anatomy. RESULTS: Simulated and acquired phantom scans were in excellent agreement. For patient scans, bony atomy registration discrepancies for ultra-low-dose scans fell within 2 mm (translation) and 1° (rotation) compared with the current clinical protocol, with excellent inter-observer agreement. Soft-tissue registration showed large discrepancies. Bone visualisation and registration performance reached over 75% acceptability (rated 'well' or 'very well') down to the lowest doses. Soft-tissue visualisation did not reach this threshold for any dose. CONCLUSION: Ultra-low-dose CBCT was accurately simulated and evaluated in patient data. Patient scans simulated down to 0.125 mGy were appropriate for bony anatomy set-up. The large dose reduction could allow for more frequent (e.g. daily) image guidance and, hence, more accurate set-up for paediatric radiotherapy.

Intratumoral nanoplexed poly I:C BO-112 in combination with systemic anti-PD-1 for patients with anti-PD-1-refractory tumors.

Intratumoral therapies, especially Toll-like receptor agonists, can trigger both the innate and adaptive immune systems. BO-112 is a nanoplexed form of polyinosinic:polycytidylic acid (poly I:C) that induces local and systemic immunotherapeutic effects in mouse models. In a multicenter phase 1 clinical trial, repeated intratumoral administrations of BO-112 induced an increase in tumor cell necrosis and apoptosis, as well as augmented immune reactivity according to gene expression profiling. The first three cohorts receiving BO-112 as a monotherapy resulted in a recommended dose of 1 mg that could be safely repeated. Two grade 3 to 4 adverse reactions in the form of reversible thrombocytopenia were reported. In a fourth cohort of 28 patients with tumors that had primary resistance to anti-programmed cell death protein-1 (PD-1), the combination of intratumoral BO-112 with nivolumab or pembrolizumab was also well tolerated, and 3 patients (2 with melanoma and 1 with renal cell carcinoma) achieved partial responses, with 10 more patients having stable disease at 8 to 12 weeks. Thus, local BO-112 combined with a systemic anti-PD-1 agent might be a strategy to revert anti-PD-1 resistance.

Radio-induced cardiotoxicity: From physiopathology and risk factors to adaptation of radiotherapy treatment planning and recommended cardiac follow-up.

Cancer and cardiovascular disease (CVD) are the leading cause of mortality worldwide, and breast cancer (BC) the most common malignancy affecting women worldwide. Radiotherapy is an important component of BC treatment and participates in CVD occurrence. It seems, therefore, crucial to gather both radiation oncology and cardiology medical fields to improve the follow-up quality of our BC patients. This review aims at updating our knowledge regarding cardiotoxicities risk factors, and consequently, doses constraints in case of 3D-conformal and IMRT treatment planning. Then we will develop how to reduce cardiac exposure and what kind of cardiac follow-up we could recommend to our breast cancer patients.

Impact of Peer Review in Reducing Uncertainty in the Definition of the Lung Target Volume Among Trainee Oncologists.

AIMS: To evaluate the impact of peer review and contouring workshops on reducing uncertainty in target volume delineation for lung cancer radiotherapy. MATERIALS AND METHODS: Data from two lung cancer target volume delineation courses were analysed. In total, 22 trainees in clinical oncology working across different UK centres attended these courses with priori experience in lung cancer radiotherapy. The courses were made up of short presentations and contouring practice sessions. The participants were divided into two groups and asked to first individually delineate (IND) and then individually peer review (IPR) the contours of another participant. The contours were discussed with an expert panel consisting of two consultant clinical oncologists and a consultant radiologist. Contours were analysed quantitatively by measuring the volume and local distance standard deviation (localSD) from the reference expert consensus contour and qualitatively through visual analysis. Feedback from the participants was obtained using a questionnaire. RESULTS: All participants applied minor editing to the contours during IPR, leading to a non-statistically significant reduction in the mean delineated volume (IND = 140.92 cm3, IPR = 125.26 cm3, P = 0.211). The overall interobserver variation was similar, with a localSD of 0.33 cm and 0.38 cm for the IND and IPR, respectively (P = 0.848). Six participants (29%) carried out correct major changes by either including tumour or excluding healthy tissue. One participant (5%) carried out an incorrect edit by excluding parts of the tumour, while another observer failed to identify a major contour error. The participants' level of confidence in target volume delineation increased following the course and identified the discussions with the radiologist and colleagues as the most important highlights of the course. CONCLUSION: IPR could improve target volume delineation quality among trainee oncologists by identifying most major contour errors. However, errors were also introduced after IPR, suggesting the need to further discuss major changes with a multidisciplinary team.

Intratumor Adoptive Transfer of IL-12 mRNA Transiently Engineered Antitumor CD8+ T Cells.

Retroviral gene transfer of interleukin-12 (IL-12) into T cells markedly enhances antitumor efficacy upon adoptive transfer but has clinically shown unacceptable severe side effects. To overcome the toxicity, we engineered tumor-specific CD8+ T cells to transiently express IL-12. Engineered T cells injected intratumorally, but not intravenously, led to complete rejections not only of the injected lesion but also of distant concomitant tumors. Efficacy was further enhanced by co-injection with agonist anti-CD137 mAb or by transient co-expression of CD137 ligand. This treatment induced epitope spreading of the endogenous CD8+ T cell immune response in a manner dependent on cDC1 dendritic cells. Mouse and human tumor-infiltrating T lymphocyte cultures can be transiently IL-12 engineered to attain marked immunotherapeutic effects.

Immunotherapeutic effects of intratumoral nanoplexed poly I:C.

Poly I:C is a powerful immune adjuvant as a result of its agonist activities on TLR-3, MDA5 and RIG-I. BO-112 is a nanoplexed formulation of Poly I:C complexed with polyethylenimine that causes tumor cell apoptosis showing immunogenic cell death features and which upon intratumoral release results in more prominent tumor infiltration by T lymphocytes. Intratumoral treatment with BO-112 of subcutaneous tumors derived from MC38, 4 T1 and B16-F10 leads to remarkable local disease control dependent on type-1 interferon and gamma-interferon. Some degree of control of non-injected tumor lesions following BO-112 intratumoral treatment was found in mice bearing bilateral B16-OVA melanomas, an activity which was enhanced with co-treatment with systemic anti-CD137 and anti-PD-L1 mAbs. More abundant CD8+ T lymphocytes were found in B16-OVA tumor-draining lymph nodes and in the tumor microenvironment following intratumoral BO-112 treatment, with enhanced numbers of tumor antigen-specific cytotoxic T lymphocytes. Genome-wide transcriptome analyses of injected tumor lesions were consistent with a marked upregulation of the type-I interferon pathway. Inspired by these data, intratumorally delivered BO-112 is being tested in cancer patients (NCT02828098).

Determination of volatile compounds and their sensory impact in a biopolymer based on polylactic acid (PLA) and polyester.

Polylactic acid (PLA) is one of the most commonly used biopolymers for manufacturing food packaging; its control is very important to ensure consumers' health. In this work, a blend of PLA and polyester was studied and its volatile composition in the polymer and in the migration to food simulants was determined by gas chromatography-mass spectrometry (GC-MS) and atmospheric pressure gas chromatography-quadrupole-time of flight mass spectrometry (APGC-QTOF). The results showed that both techniques provided complementary information, to give complete information on the biopolymer's composition. Some compounds such as lactide or cyclopentanone were detected only by GC-MS while others, such as the cyclic dimer [AA-BD]2 (AA:adipic acid, BD:butanediol), were detected only by APGC-MS. In migration, lactide, AA-BD and [AA-BD]2 were identified in ethanol 95%. A GC-olfactometry study was also carried out. Some compounds showed sensory impact on the polymer odor but not in migration.

Prevalence and risk factors of multidrug-resistant tuberculosis in Cubal, Angola: a prospective cohort study.

BACKGROUND: Although the Republic of Angola is one of the 14 countries figuring in the three high tuberculosis (TB) burden country lists, the true multidrug-resistant TB (MDR-TB) situation is unknown. MATERIAL AND METHODS: Patients aged 16 years with a diagnosis of pulmonary TB were prospectively enrolled from June 2014 to July 2015. Sputum samples were collected for culture and drug susceptibility testing in all patients, and for Xpert® MTB/RIF testing in all previously treated patients and in new patients whose sputum remained smear-positive after 2 months of treatment. RESULTS: A total of 422 patients were included; Mycobacterium tuberculosis was isolated in 308 sputum samples. The prevalence of MDR-TB was 8.0% (18/225) in new patients and 71.1% (59/83) in previously treated patients. Male sex (OR 2.95, 95%CI 1.35-6.44, P = 0.007), previous anti-tuberculosis treatment (OR 20.86, 95%CI 9.53-45.67, P < 0.001), presence of pleural thickening (OR 7.68, 95%CI 1.57-37.43, P = 0.012) and duration of illness >4 months (OR 3.34, 95%CI 1.45-7.69, P = 0.005) were independent risk factors for MDR-TB. CONCLUSIONS: The prevalence of MDR-TB in Cubal, Angola, was higher than estimated by the World Health Organization for Angola and one of the highest worldwide. Facilities to diagnose and treat MDR-TB are urgently needed in Angola.