A YY1 bridge for X inactivation.

Xist RNA inactivates one mammalian X chromosome (the Xi) by associating with it in cis. The mechanism of this interaction is unresolved. Jeon and Lee (2011) now show that YY1 binds both Xist RNA and DNA, thereby providing a mechanism to anchor Xist to the Xi and facilitate X chromosome inactivation.

Microscopy of Woven and Nonwoven Face Covering Materials: Implications for Particle Filtration.

A suite of natural, synthetic, and mixed synthetic-natural woven fabrics, along with nonwoven filtration layers from a surgical mask and an N95 respirator, was examined using visible light microscopy, scanning electron microscopy, and micro-X-ray computed tomography (µXCT) to determine the fiber diameter distribution, fabric thickness, and the volume of solid space of the fabrics. Nonwoven materials exhibit a positively skewed distribution of fiber diameters with a mean value of ≈3 µm, whereas woven fabrics exhibit a normal distribution of diameters with mean values roughly five times larger (>15 µm). The mean thickness of the N95 filtration material is 1093 µm and is greater than that of the woven fabrics that span from 420 to 650 µm. A new procedure for measuring the thickness of flannel fabrics is proposed that accounts for raised fibers. µXCT allowed for a quantitative nondestructive approach to measure fabric porosity as well as the surface area/volume. Cotton flannel showed the largest mean isotropy of any fabric, though fiber order within the weave is poorly represented in the surface electron images. Surface fabric isotropy and surface area/volume ratios are proposed as useful microstructural quantities to consider for future particle filtration modeling efforts of woven materials.

The need for ambulatory emergency oncology: exemplified by the management of immune checkpoint inhibitor toxicity.

Cancer patients seeking emergency care can be vulnerable in increasingly overcrowded Emergency Departments and timely delivery of care is often aspirational rather than reality in many acute care systems. Ambulatory emergency care and its various international models are recognized as contributing to the safety and sustainability of emergency care services. This schema can logically be extended to the emergency oncology setting. The recent proliferation of immune checkpoint inhibitors (ICIs) has led to another opportunity for the management of oncologic complications in the ambulatory emergency care setting. More nuanced risk stratification of currently perceived high-risk toxicities may also afford the opportunity to personalize acute management. Virtual wards, which predominantly provide virtual monitoring only, and hospital at home services, which provide more comprehensive in-person assessment and interventions, may be well suited to supporting care for ICI toxicity alongside hospital-based assessment. Emergency management guidelines for immune-mediated toxicities will increasingly need to be both pragmatic and deliverable, especially as larger numbers of patients will present outside cancer centers. Identifying and modelling those suitable for emergency ambulatory care is integral to achieving this.

Improved outcomes with early immunosuppression in patients with immune-checkpoint inhibitor induced myasthenia gravis, myocarditis and myositis: a case series.

PURPOSE: Myasthenia gravis (MG) is a rare but life-threatening complication of immune-checkpoint inhibitor (ICI) therapy and often co-presents with myositis and myocarditis. Previous case series of ICI-related MG have reported high mortality rates. We present a series of ten patients from a tertiary oncology centre outlining outcomes of an early multi-modal immunosuppression strategy. METHODS: We reviewed The Christie Hospital database of immunotherapy-related toxicity from 2017 to 2020. Symptom severity was assessed using the Myasthenia Gravis Foundation of America (MGFA) classification. RESULTS: Ten patients with ICI-related MG were identified. All patients presented following 1 (n = 4) or 2 (n = 6) cycles of ICI. Symptom progression was rapid with a median of 3 days from onset of symptoms to admission. Concomitant myositis and myocarditis were observed in nine patients. AChR or MuSK autoantibodies were positive in six patients. All patients received urgent treatment with intravenous methylprednisolone (IVMP) and eight received intravenous immunoglobulin (IVIG). A single patient died from myasthenia-related symptoms; the remaining 9 patients were successfully discharged. CONCLUSION: In our cohort, we demonstrate good outcomes associated with early intensive immunosuppressive treatment with IVIG and IVMP. An agreed national treatment protocol or clinical discussion forum would be beneficial.

Low-cost and clinically applicable copy number profiling using repeat DNA.

BACKGROUND: Somatic copy number alterations (SCNAs) are an important class of genomic alteration in cancer. They are frequently observed in cancer samples, with studies showing that, on average, SCNAs affect 34% of a cancer cell's genome. Furthermore, SCNAs have been shown to be major drivers of tumour development and have been associated with response to therapy and prognosis. Large-scale cancer genome studies suggest that tumours are driven by somatic copy number alterations (SCNAs) or single-nucleotide variants (SNVs). Despite the frequency of SCNAs and their clinical relevance, the use of genomics assays in the clinic is biased towards targeted gene panels, which identify SNVs but provide limited scope to detect SCNAs throughout the genome. There is a need for a comparably low-cost and simple method for high-resolution SCNA profiling. RESULTS: We present conliga, a fully probabilistic method that infers SCNA profiles from a low-cost, simple, and clinically-relevant assay (FAST-SeqS). When applied to 11 high-purity oesophageal adenocarcinoma samples, we obtain good agreement (Spearman's rank correlation coefficient, rs=0.94) between conliga's inferred SCNA profiles using FAST-SeqS data (approximately £14 per sample) and those inferred by ASCAT using high-coverage WGS (gold-standard). We find that conliga outperforms CNVkit (rs=0.89), also applied to FAST-SeqS data, and is comparable to QDNAseq (rs=0.96) applied to low-coverage WGS, which is approximately four-fold more expensive, more laborious and less clinically-relevant. By performing an in silico dilution series experiment, we find that conliga is particularly suited to detecting SCNAs in low tumour purity samples. At two million reads per sample, conliga is able to detect SCNAs in all nine samples at 3% tumour purity and as low as 0.5% purity in one sample. Crucially, we show that conliga's hidden state information can be used to decide when a sample is abnormal or normal, whereas CNVkit and QDNAseq cannot provide this critical information. CONCLUSIONS: We show that conliga provides high-resolution SCNA profiles using a convenient, low-cost assay. We believe conliga makes FAST-SeqS a more clinically valuable assay as well as a useful research tool, enabling inexpensive and fast copy number profiling of pre-malignant and cancer samples.

Pandemic fluoroquinolone resistant Escherichia coli clone ST1193 emerged via simultaneous homologous recombinations in 11 gene loci.

Global growth in antibiotic resistance is a major social problem. A high level of resistance to fluoroquinolones requires the concurrent presence of at least 3 mutations in the target proteins-2 in DNA gyrase (GyrA) and 1 in topoisomerase IV (ParC), which occur in a stepwise manner. In the Escherichia coli chromosome, the gyrA and parC loci are positioned about 1 Mb away from each other. Here we show that the 3 fluoroquinolone resistance mutations are tightly associated genetically in naturally occurring strains. In the latest pandemic uropathogenic and multidrug-resistant E. coli clonal group ST1193, the mutant variants of gyrA and parC were acquired not by a typical gradual, stepwise evolution but all at once. This happened as part of 11 simultaneous homologous recombination events involving 2 phylogenetically distant strains of E. coli, from an uropathogenic clonal complex ST14 and fluoroquinolone-resistant ST10. The gene exchanges swapped regions between 0.5 and 139 Kb in length (183 Kb total) spread along 976 Kb of chromosomal DNA around and between gyrA and parC loci. As a result, all 3 fluoroquinolone resistance mutations in GyrA and ParC have simultaneously appeared in ST1193. Based on molecular clock estimates, this potentially happened as recently as <12 y ago. Thus, naturally occurring homologous recombination events between 2 strains can involve numerous chromosomal gene locations simultaneously, resulting in the transfer of distant but tightly associated genetic mutations and emergence of a both highly pathogenic and antibiotic-resistant strain with a rapid global spread capability.

A comparative analysis of whole genome sequencing of esophageal adenocarcinoma pre- and post-chemotherapy.

The scientific community has avoided using tissue samples from patients that have been exposed to systemic chemotherapy to infer the genomic landscape of a given cancer. Esophageal adenocarcinoma is a heterogeneous, chemoresistant tumor for which the availability and size of pretreatment endoscopic samples are limiting. This study compares whole-genome sequencing data obtained from chemo-naive and chemo-treated samples. The quality of whole-genomic sequencing data is comparable across all samples regardless of chemotherapy status. Inclusion of samples collected post-chemotherapy increased the proportion of late-stage tumors. When comparing matched pre- and post-chemotherapy samples from 10 cases, the mutational signatures, copy number, and SNV mutational profiles reflect the expected heterogeneity in this disease. Analysis of SNVs in relation to allele-specific copy-number changes pinpoints the common ancestor to a point prior to chemotherapy. For cases in which pre- and post-chemotherapy samples do show substantial differences, the timing of the divergence is near-synchronous with endoreduplication. Comparison across a large prospective cohort (62 treatment-naive, 58 chemotherapy-treated samples) reveals no significant differences in the overall mutation rate, mutation signatures, specific recurrent point mutations, or copy-number events in respect to chemotherapy status. In conclusion, whole-genome sequencing of samples obtained following neoadjuvant chemotherapy is representative of the genomic landscape of esophageal adenocarcinoma. Excluding these samples reduces the material available for cataloging and introduces a bias toward the earlier stages of cancer.

Rapid and Extensive Expansion in the United States of a New Multidrug-resistant Escherichia coli Clonal Group, Sequence Type 1193.

We describe the rapid and ongoing emergence across multiple US cities of a new multidrug-resistant Escherichia coli clone-sequence type (ST) 1193-resistant to fluoroquinolones (100%), trimethoprim-sulfamethoxazole (55%), and tetracycline (53%). ST1193 is associated with younger adults (age <40 years) and currently comprises a quarter of fluoroquinolone-resistant clinical E. coli urine isolates.

Properties of Pertechnic Acid.

Dilute aqueous pertechnic acid has long been known as strong monoprotic acid that behaves as a simple pertechnetate ion in aqueous solution. As pertechnic acid concentrates by evaporation, it becomes yellow and then dark red, and dark-red crystalline material may ultimately be obtained. We show that as pertechnic acid concentrates, at least three compounds are formed: a yellow viscous liquid, a colorless (not red) crystalline solid, and a small amount of an intensely colored red-purple compound. The colorless crystalline compound melts at 118 °C and can be melted and recrystallized several times with little decomposition. The red-purple compound is apparently not stable at room temperature and quickly decomposes if it is isolated. UV-vis spectra show that Beer's law does not hold as pertechnic acid concentrates by evaporation. We report densities, 99Tc nuclear magnetic resonance spectra, and ultraviolet-visible absorption spectra for highly pure aqueous pertechnic acid (accompanied by the other technetium compounds that form) ranging from 1 to 14 M in technetium concentration.

Predictive factors of thromboembolic complications in patients with esophagogatric adenocarcinoma undergoing preoperative chemotherapy.

BACKGROUND: Thromboembolic events (TEEs) represent a significant treatment and disease complication for cancer patients. In the present study we assessed the incidence of TEEs in patients receiving preoperative chemotherapy for esophagogastric adenocarcinoma. The risk factors for TEE development and their impact on prognosis were further analyzed. MATERIAL AND METHODS: Data from 590 patients with esophagogastric adenocarcinoma, who received preoperative epirubicin-cisplatin with capecitabine (ECX) or 5-fluorouracil (ECF) between 2009 and 2016 in three UK hospitals were retrospectively collected. RESULTS: Twenty-one percent had stomach primary and 98% received ECX chemotherapy. In total, 52 patients (9%) had a venous and 22 (4%) an arterial event. Of those patients with venous TEEs (vTTEs), 39 had pulmonary embolism and 13 deep vein thrombosis, whereas in patients with arterial TEEs (arTTEs), 7 developed a myocardial infarct, 8 developed limb ischemia, 4 developed cerebrovascular accidents and 3 developed superior mesenteric artery thrombosis. ArTEEs were associated with a much higher inoperability rate compared to cases without TEE or with vTEE (77% vs. 20% vs. 31%, respectively, p < .001). Independent risk factors of vTEEs were primary site being the stomach (Odds ratio [OR] 3.24, 95%CI 1.72-6.12, p < .001), being overweight (OR 3.11, 95%CI 1.33-7.26, p = .009) or obese (OR 4.52, 95%CI 1.85-11.09, p = .001) and the presence of central venous access device (OR 3.40, 95%CI 1.00-11.55, p = .050). In contrast, anticoagulant treatment was independently associated with a lower risk of vTEE (OR 0.22, 95%CI 0.06-0.83, p = .026). Khorana score of 4-5 was an independent risk factor of arTEE (OR 6.38, 95%CI 1.85-22.04, p = .003). Finally, arTEEs were an independent poor prognostic factor for OS, when adjusted for baseline patient, tumor and treatment characteristics (Hazard ratio 3.02, 95%CI 1.85-4.95, p < .001). CONCLUSION: Preoperative ECX/ECF chemotherapy for patients with resectable esophagogastric adenocarcinoma was associated with relatively high incidence of TEEs. However, only arTEEs affected patient survival outcomes.

Natural alteration of 6Li alumino-silicate glass.

Understanding the chemical durability of neutron shielding materials is necessary when assessing their long-term service potential. In this study, the chemical durability of a 6Li enriched neutron shielding glass that has been exposed to natural, near-operational conditions is assessed by Prompt Gamma Activation Analysis (PGAA) and Neutron Depth Profiling (NDP). These non-destructive, nuclear analysis techniques are sensitive to 6Li, and PGAA is uniquely able to detect H in low quantities in solids. It was determined that the enriched alumino-silicate glass can alter within 2 months of exposure to the natural environment. This exposure resulted in an average surface alteration layer thickness of ≈22 µm. The alteration layer contained ≈47% less 6Li than the bulk glass. Alternatively, a 3 years exposed sample of the glass had a surface alteration depth of ≈30 µm and 6Li depletion levels in the alteration layer were between 47% and 75% less 6Li than the bulk glass. When the alteration layer on the 3 years sample was removed, the H content of the glass's surface was nearly eliminated. This sample also showed variable Li concentrations throughout the alteration volume, which contrasts with near static Li concentration in the alteration volume of the 2 months sample. From these findings it was determined that the depletion in Li at the surface of the glass will not affect the glass's neutron shielding properties, but it may change the mechanical stability of the glass's surface and, due to increased H content in the alteration layer, make it an inappropriate material for the lining of certain neutron analysis instruments.

Chemical Trends in Solid Alkali Pertechnetates.

Insight into the solid-state chemistry of pure technetium-99 (99Tc) oxides is required in the development of a robust immobilization and disposal system for nuclear waste stemming from the radiopharmaceutical industry, from the production of nuclear weapons, and from spent nuclear fuel. However, because of its radiotoxicity and the subsequent requirement of special facilities and handling procedures for research, only a few studies have been completed, many of which are over 20 years old. In this study, we report the synthesis of pure alkali pertechnetates (sodium, potassium, rubidium, and cesium) and analysis of these compounds by Raman spectroscopy, X-ray absorption spectroscopy (XANES and EXAFS), solid-state nuclear magnetic resonance (static and magic angle spinning), and neutron diffraction. The structures and spectral signatures of these compounds will aid in refining the understanding of 99Tc incorporation into and release from nuclear waste glasses. NaTcO4 shows aspects of the relatively higher electronegativity of the Na atom, resulting in large distortions of the pertechnetate tetrahedron and deshielding of the 99Tc nucleus relative to the aqueous TcO4-. At the other extreme, the large Cs and Rb atoms interact only weakly with the pertechnetate, have closer to perfect tetrahedral symmetry at the Tc atom, and have very similar vibrational spectra, even though the crystal structure of CsTcO4 is orthorhombic while that of RbTcO4 is tetragonal. Further trends are observed in the cell volume and quadrupolar coupling constant.

Significance of baseline FDG-PET/CT scan as a method of staging regional lymph nodes in patients with operable distal oesophageal or gastroesophageal junction adenocarcinoma.

BACKGROUND: The new American Joint Committee on Cancer eighth edition (AJCC8) staging is the first to describe separate clinical and pathology staging systems, but still has low performance to predict prognosis in patients with oesophageal/gastroesophageal junction (O/GOJ) adenocarcinoma, who are candidates for surgery. Recent studies have demonstrated that O/GOJ cancer patients with 18F-fluorodeoxyglucose (FDG) avid regional lymph nodes (RLNs) may have poor prognosis. The aim of our study was to examine whether the baseline assessment of the FDG uptake of RLN improves the prognostic accuracy of the new AJCC8 staging. PATIENTS AND METHODS: This single-centre retrospective study included patients with operable FDG avid O/GOJ adenocarcinoma treated with perioperative chemotherapy. All patients were reclassified according to the new AJCC8 clinical staging. Prognostic factors for time-to-progression (TTP) and overall survival (OS) were explored. RESULTS: Of 430 patients included in the study, 180 (41.9%) had FDG avid RLN at baseline PET/CT scan before starting perioperative chemotherapy. The presence of FDG avid RLN was significantly and independently associated with shorter TTP and OS, especially in clinical stage III patients (p < .001 in both cases). Stage III patients with FDG avid RLN had similar TTP and OS to those with stage IVA. Classifying stage III patients with FDG avid RLN into stage IVA led to a significant improvement of the prognostic accuracy of the new AJCC8 clinical staging system (Harrell's concordance index improved from 0.555 to 0.588, p < .001). Of 430 patients starting perioperative chemotherapy, 332 underwent radical tumour resection. The presence of FDG avid RLN before starting perioperative chemotherapy could additionally predict a significantly shorter postoperative time-to-relapse and OS (p < .001 in both cases). CONCLUSIONS: We propose that the incorporation of RLN status (by FDG PET/CT scan) into the AJCC8 staging system of O/GOJ adenocarcinoma improves its prognostic accuracy and may also improve treatment stratification.

Chromatin regulators of genomic imprinting.

Genomic imprinting is an epigenetic phenomenon in which genes are expressed monoallelically in a parent-of-origin-specific manner. Each chromosome is imprinted with its parental identity. Here we will discuss the nature of this imprinting mark. DNA methylation has a well-established central role in imprinting, and the details of DNA methylation dynamics and the mechanisms that target it to imprinted loci are areas of active investigation. However, there is increasing evidence that DNA methylation is not solely responsible for imprinted expression. At the same time, there is growing appreciation for the contributions of post-translational histone modifications to the regulation of imprinting. The integration of our understanding of these two mechanisms is an important goal for the future of the imprinting field. This article is part of a Special Issue entitled: Chromatin and epigenetic regulation of animal development.

Mobile element insertions are frequent in oesophageal adenocarcinomas and can mislead paired-end sequencing analysis.

BACKGROUND: Mobile elements are active in the human genome, both in the germline and cancers, where they can mutate driver genes. RESULTS: While analysing whole genome paired-end sequencing of oesophageal adenocarcinomas to find genomic rearrangements, we identified three ways in which new mobile element insertions appear in the data, resembling translocation or insertion junctions: inserts where unique sequence has been transduced by an L1 (Long interspersed element 1) mobile element; novel inserts that are confidently, but often incorrectly, mapped by alignment software to L1s or polyA tracts in the reference sequence; and a combination of these two ways, where different sequences within one insert are mapped to different loci. We identified nine unique sequences that were transduced by neighbouring L1s, both L1s in the reference genome and L1s not present in the reference. Many of the resulting inserts were small fragments that include little or no recognisable mobile element sequence. We found 6 loci in the reference genome to which sequence reads from inserts were frequently mapped, probably erroneously, by alignment software: these were either L1 sequence or particularly long polyA runs. Inserts identified from such apparent rearrangement junctions averaged 16 inserts/tumour, range 0-153 insertions in 43 tumours. However, many inserts would not be detected by mapping the sequences to the reference genome, because they do not include sufficient mappable sequence. To estimate total somatic inserts we searched for polyA sequences that were not present in the matched normal or other normals from the same tumour batch, and were not associated with known polymorphisms. Samples of these candidate inserts were verified by sequencing across them or manual inspection of surrounding reads: at least 85 % were somatic and resembled L1-mediated events, most including L1Hs sequence. Approximately 100 such inserts were detected per tumour on average (range zero to approximately 700). CONCLUSIONS: Somatic mobile elements insertions are abundant in these tumours, with over 75 % of cases having a number of novel inserts detected. The inserts create a variety of problems for the interpretation of paired-end sequencing data.

Xaml1/Runx1 is required for the specification of Rohon-Beard sensory neurons in Xenopus.

Lower vertebrates develop a unique set of primary sensory neurons located in the dorsal spinal cord. These cells, known as Rohon-Beard (RB) sensory neurons, innervate the skin and mediate the response to touch during larval stages. Here we report the expression and function of the transcription factor Xaml1/Runx1 during RB sensory neurons formation. In Xenopus embryos Runx1 is specifically expressed in RB progenitors at the end of gastrulation. Runx1 expression is positively regulated by Fgf and canonical Wnt signaling and negatively regulated by Notch signaling, the same set of factors that control the development of other neural plate border cell types, i.e. the neural crest and cranial placodes. Embryos lacking Runx1 function fail to differentiate RB sensory neurons and lose the mechanosensory response to touch. At early stages Runx1 knockdown results in a RB progenitor-specific loss of expression of Pak3, a p21-activated kinase that promotes cell cycle withdrawal, and of N-tub, a neuronal-specific tubulin. Interestingly, the pro-neural gene Ngnr1, an upstream regulator of Pak3 and N-tub, is either unaffected or expanded in these embryos, suggesting the existence of two distinct regulatory pathways controlling sensory neuron formation in Xenopus. Consistent with this possibility Ngnr1 is not sufficient to activate Runx1 expression in the ectoderm. We propose that Runx1 function is critically required for the generation of RB sensory neurons, an activity reminiscent of that of Runx1 in the development of the mammalian dorsal root ganglion nociceptive sensory neurons.

Intensive care unit requirements in patients treated with immune checkpoint inhibitors.

OBJECTIVE: To determine the proportion of emergency patients treated with immune checkpoint inhibitors (ICIs) that require critical care admission and their requirements. DESIGN: Prospective case series. METHODS: Analysis of acutely unwell patients treated with ICIs attending a tertiary UK cancer hospital between May 2018 and May 2022. The primary outcome measure was the percentage of patients treated with ICI therapy requiring ICU admission. The secondary outcome measure was whether this need was driven by an immune-mediated toxicity. RESULTS: Eighteen (1.2%) patients of the 1561 acutely admitted patients treated with ICI therapy required an admission to ICU. Ten (55.5%) patients were admitted due to an immune-mediated toxicity; four due to pneumonitis and four due to myasthenia gravis. Seven of 10 survived their ICU admission with 6 surviving at least 6-month post-ICU discharge. CONCLUSIONS: Only a small minority of emergency admissions in patients treated with ICIs require admission to ICU. This series adds further evidence that patients with organ failure due to immune-mediated toxicity may achieve good outcomes from ICU admission.

Selection of Chemotherapy in Advanced Poorly Differentiated Extra-Pulmonary Neuroendocrine Carcinoma.

Extra-pulmonary poorly differentiated neuroendocrine carcinoma is rare, and evidence for treatment has been limited. In this article, the evidence behind the cytotoxic chemotherapy choices used for metastatic or unresectable EP-PD-NEC is reviewed. In the first-line setting, etoposide and platinum chemotherapy or irinotecan and platinum have been demonstrated to be equivalent in a large phase III trial. Questions remain regarding the optimal number of cycles, mode of delivery, and the precise definition of platinum resistance in this setting. In the second-line setting, FOLFIRI has emerged as an option, with randomized phase 2 trials demonstrating modest, but significant, response rates. Beyond this, data are extremely limited, and several regimens have been used. Heterogeneity in biological behaviour is a major barrier to optimal EP-PD-NEC management. Available data support the potential role of the Ki-67 index as a predictive biomarker for chemotherapy response. A more personalised approach to management in future studies will be essential, and comprehensive multi-omic approaches are required to understand tumour somatic genetic changes in relation to their effects on the surrounding microenvironment.

Low muscle mass measured at T12 is a prognostic biomarker in unresectable oesophageal cancers receiving chemoradiotherapy.

BACKGROUND AND PURPOSE: Low muscle mass is an imaging biomarker of patient frailty that has been associated with increased toxicity and decreased survival in a number of cancers. Patients with unresectable oesophageal cancer receive chemoradiotherapy as standard of care. Muscle mass is not yet an established prognostic marker in this population. Muscle mass is usually assessed by segmenting skeletal muscle at the L3 vertebral level. But radiotherapy planning scans for oesophageal cancers do not always image this level, which has limited previous studies of body composition. Skeletal muscle is known to regulate immune function, but the association of muscle mass with lymphopenia in cancer patients has not been shown. MATERIALS AND METHODS: We retrospectively analyse 135 oesophageal cancer patients who received chemoradiotherapy and investigate the prognostic value of skeletal muscle area assessed at T12. We also examine the association between muscle mass and radiation-induced lymphopenia. RESULTS: We find that low muscle mass is associated with poorer overall survival (hazard ratio [95% confidence interval]: 0.72 [0.53-0.97]). However, this effect interacts with body mass index (BMI) such that the prognostic value of low muscle mass is removed by high BMI. In our study, patients with low muscle mass were more prone to radiation-induced lymphopenia (75% vs. 50% in patients with high muscle mass). A significant decrease in circulating lymphocytes was associated with poorer overall survival (hazard ratio [95% confidence interval]: 0.68 [0.47-0.99]). CONCLUSION: Our study shows that assessing muscle mass at T12 is feasible and provides prognostic information. Low muscle mass at T12 is associated with poorer overall survival and increased risk of radiation-induced lymphopenia. Muscle mass provides additional information over performance status and BMI. Low BMI patients are most affected by low muscle mass, highlighting the importance of close nutritional support in this population.