Latha Kadalayil - Academia.edu (original) (raw)

Papers by Latha Kadalayil

Clinical Epigenetics

Background Seasonal variations in environmental exposures at birth or during gestation are associ... more Background Seasonal variations in environmental exposures at birth or during gestation are associated with numerous adult traits and health outcomes later in life. Whether DNA methylation (DNAm) plays a role in the molecular mechanisms underlying the associations between birth season and lifelong phenotypes remains unclear. Methods We carried out epigenome-wide meta-analyses within the Pregnancy And Childhood Epigenetic Consortium to identify associations of DNAm with birth season, both at differentially methylated probes (DMPs) and regions (DMRs). Associations were examined at two time points: at birth (21 cohorts, N = 9358) and in children aged 1–11 years (12 cohorts, N = 3610). We conducted meta-analyses to assess the impact of latitude on birth season-specific associations at both time points. Results We identified associations between birth season and DNAm (False Discovery Rate-adjusted p values < 0.05) at two CpGs at birth (winter-born) and four in the childhood (summer-bor...

Lancet Oncology, Mar 1, 2017

Background Guidelines for anal cancer recommend assessment of response at 6-12 weeks after starti... more Background Guidelines for anal cancer recommend assessment of response at 6-12 weeks after starting treatment. Using data from the ACT II trial, we determined the optimum timepoint to assess clinical tumour response after chemoradiotherapy. Methods The previously reported ACT II trial was a phase 3 randomised trial of patients of any age with newly diagnosed, histologically confirmed, squamous cell carcinoma of the anus without metastatic disease from 59 centres in the UK. We randomly assigned patients (by minimisation) to receive either intravenous mitomycin (one dose of 12 mg/m² on day 1) or intravenous cisplatin (one dose of 60 mg/m² on days 1 and 29), with intravenous fluorouracil (one dose of 1000 mg/m² per day on days 1-4 and 29-32) and radiotherapy (50•4 Gy in 28 daily fractions); and also did a second randomisation after initial therapy to maintenance chemotherapy (fluorouracil and cisplatin) or no maintenance chemotherapy. The primary outcome was complete clinical response (the absence of primary and nodal tumour by clinical examination), in addition to overall survival and progression-free survival from time of randomisation. In this post-hoc analysis, we analysed complete clinical response at three timepoints: 11 weeks from the start of chemoradiotherapy (assessment 1), 18 weeks from the start of chemoradiotherapy (assessment 2), and 26 weeks from the start of chemoradiotherapy (assessment 3) as well as the overall and progression-free survival estimates of patients with complete clinical response or without complete clinical response at each assessment. We analysed both the overall trial population and a subgroup of patients who had attended each of the three assessments by modified intention-to-treat. This study is registered at controlled-trials. com, ISRCTN 26715889.

Pediatric Allergy and Immunology, Apr 1, 2022

Epigenomics, Apr 1, 2021

Aim: Agreement in DNA methylation (DNAm) at the genome scale between blood leukocytes (BL) and br... more Aim: Agreement in DNA methylation (DNAm) at the genome scale between blood leukocytes (BL) and bronchial epithelial cells (BEC) is unknown. We examine as to what extent DNAm in BL is comparable with that in BEC and serves as a surrogate for BEC. Methods: Overall agreement (paired t-tests with false discovery rate adjusted p-value >0.05) and consistency (Pearson's correlation coefficients >0.5) between two tissues, at each of the 767,412 CpGs, were evaluated. Results & Conclusion: We identified 247,721 CpGs showing overall agreement and 47,371 CpGs showing consistency in DNAm. Identified CpGs are involved in certain immune pathways, indicating the potential of using blood as a biomarker for BEC at those CpGs in lower airwayrelated diseases. CpGs showing overall agreement and those without overall agreement are distributed differently on the genome.

Clinical & Experimental Allergy, Nov 25, 2020

Background-Underlying biological mechanisms involved in sex differences in asthma status changes ... more Background-Underlying biological mechanisms involved in sex differences in asthma status changes from pre-to post-adolescence are unclear. DNA methylation (DNAm) has been shown to be associated with the risk of asthma. Objective-We hypothesized that asthma acquisition from pre-to post-adolescence was associated with changes in DNAm during this period at asthma-associated cytosine-phosphateguanine (CpG) sites and such an association was sex-specific. Methods-Subjects from the Isle of Wight birth cohort (IOWBC) with DNAm in blood at ages 10 and 18 years (n=124 females, 151 males) were studied. Using a training-testing approach, epigenome-wide CpGs associated with asthma were identified. Logistic regression was used to examine sex-specific associations of DNAm changes with asthma acquisition between ages 10 and 18 at asthma-associated CpGs. The ALSPAC birth cohort was used for independent replication. To assess functional relevance of identified CpGs, association of DNAm with gene expression in blood was assessed. Results-We identified 535 CpGs potentially associated with asthma. Significant interaction effects of DNAm changes and sex on asthma acquisition in adolescence were found at 13 of the 535 CpGs in IOWBC (p-values<1.0×10-3). In the replication cohort, consistent interaction effects were observed at 10 of the 13 CpGs. At 7 of these 10 CpGs, opposite DNAm changes across adolescence were observed between sexes in both cohorts. Conclusion-Gender-reversal in asthma acquisition is associated with opposite changes in DNAm (males vs females) from pre-to post-adolescence at asthma-associated CpGs. These CpGs are potential biomarkers of sex-specific asthma acquisition in adolescence.

A reduction in monomer consumption in the solid phase synthesis of oligodeoxyribonucleotides has ... more A reduction in monomer consumption in the solid phase synthesis of oligodeoxyribonucleotides has been achieved by introducing a repeat coupling approach. Additionally, a method of anion exchange HPLC- purification of the synthesized nucleotides at room temperature has been developed in which a highly volatile buffer was used as the eluent. An alternative approach of HPLC purification of oligonucleotides is also reported.

Briefings in Bioinformatics, Aug 28, 2014

Copy number variants (CNVs) play important roles in a number of human diseases and in pharmacogen... more Copy number variants (CNVs) play important roles in a number of human diseases and in pharmacogenetics. Powerful methods exist for CNV detection in whole genome sequencing (WGS) data, but such data are costly to obtain. Many disease causal CNVs span or are found in genome coding regions (exons), which makes CNV detection using whole exome sequencing (WES) data attractive. If reliably validated against WGS-based CNVs, exome-derived CNVs have potential applications in a clinical setting. Several algorithms have been developed to exploit exome data for CNVdetection and comparisons made to find the most suitable methods for particular data samples.The results are not consistent across studies. Here, we review some of the exome CNV detection methods based on depth of coverage profiles and examine their performance to identify problems contributing to discrepancies in published results. We also present a streamlined strategy that uses a single metric, the likelihood ratio, to compare exome methods, and we demonstrated its utility using the VarScan 2 and eXome Hidden Markov Model (XHMM) programs using paired normal and tumour exome data from chronic lymphocytic leukaemia patients. We use array-based somatic CNV (SCNV) calls as a reference standard to compute prevalence-independent statistics, such as sensitivity, specificity and likelihood ratio, for validation of the exome-derived SCNVs.We also account for factors known to influence the performance of exome read depth methods, such as CNV size and frequency, while comparing our findings with published results.

EMBO Reports, Oct 1, 2000

The Rel/NF-κB transcription factor Relish plays a key role in the humoral immune response in Dros... more The Rel/NF-κB transcription factor Relish plays a key role in the humoral immune response in Drosophila. We now find that activation of this innate immune response is preceded by rapid proteolytic cleavage of Relish into two parts. An Nterminal fragment, containing the DNA-binding Rel homology domain, translocates to the nucleus where it binds to the promoter of the Cecropin A1 gene and probably to the promoters of other antimicrobial peptide genes. The Cterminal IκB-like fragment remains in the cytoplasm. This endoproteolytic cleavage does not involve the proteasome, requires the DREDD caspase, and is different from previously described mechanisms for Rel factor activation.

Familial studies were among the first to indicate that breast cancer prognosis has a heritable co... more Familial studies were among the first to indicate that breast cancer prognosis has a heritable component. Subsequently many variants associated with prognosis have been identified using a range of techniques including genome-wide association studies (GWAs). Despite these advances, much of the heritability remains unexplained. In young women, breast cancer is characterised by a higher incidence of adverse pathological features, unique tumour gene expression profiles and worse survival. In addition, the association of risk with conventional epidemiological exposures is less clear in women with early onset. We hypothesise that some of these difference between early and late onset could be influenced by germline variation. To identify additional variants that influence breast cancer prognosis we conducted a two stage meta-analysis of four GWAs consisting of 6,042 patients from the UK (POSH), Finland (HEBCS), Germany (SUCCESS-A) and Australia (ABCFS). Cox-regression analyses were used to investigate overall survival (OS, n=1,101 events) and disease-free survival (DFS, n=1,316 events) with correction for oestrogen status (ER). These survival analyses were repeated in a subset of patients with early onset (aged ≤40 at diagnosis, n=2,315 patients, OS n=604 events, DFS n=716 events). Meta-analysis identified two intronic SNPs in ADAMTSL1 that were associated exclusively with early onset DFS, rs715212 (Pmeta=3.54x10-5) and rs10963755 (Pmeta=3.91x10-4) without heterogeneity between cohorts. Multivariable Cox-regression demonstrated that the effect of these SNPs were independent of the classical prognostic factors. Most importantly, rs715212 reached genome-wide significance (Pmultivariate=5.37x10-8) in the multivariate model. ADAMTSL1 encodes a glycoprotein that forms part of the extracellular matrix (ECM) and may function in cell-cell or cell-matrix interactions or may regulate other ADAMTS proteases. Previous studies have shown that ADAMTSL1 is hypermethylated in ER positive breast cancer tumours. Using GTEx to perform eQTL analysis, we found that rs715212 is associated with the expression of several biologically relevant genes AREG (P=0.035), TNF (P=0.015), FASLG (P=0.0031) and EGF (P=0.0018) in breast mammary tissue. Interestingly, separate studies have shown that AREG is overexpressed in ER-positive breast tumours from pre-menopausal women versus post-menopausal women. Furthermore, AREG is differentially expressed between parous and non-parous mammary glands and is persistently downregulated by parity, which suggests it may contribute to the susceptibility of the nulliparous gland to breast cancer. We conclude that rs715212 is associated with an increased risk of disease progression in patients with early onset and speculate that this could be due to an interaction with the expression of AREG. Note: This abstract was not presented at the meeting. Citation Format: Latha Kadalayil, Sofia Khan, Heli Nevanlinna, Peter A. Fasching, Fergus J. Couch, John Hopper, Jianjun Liu, Tom Maishman, Lorraine Durcan, Carl Bloomqvist, Andy Collins, Dianna Eccles, William Tapper. A meta-analysis of genome-wide association studies identifies novel loci that influence breast cancer prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1322. doi:10.1158/1538-7445.AM2017-1322

Journal of Clinical Oncology, May 20, 2012

4029 Background: Concurrent chemoradiation (CRT) is standard treatment for patients with squamous... more 4029 Background: Concurrent chemoradiation (CRT) is standard treatment for patients with squamous cell carcinoma of the anus. Although the majority of patients achieve long term disease control, locoregional failure is either detected early (failure to enter complete remission) or at a later date as locoregional recurrence. We explore the pattern and timing of disease recurrence within a phase III trial (ACT II), which mandated standardised radiation fields and doses (50.4Gy in 28 daily fractions). Methods: The UK ACT II trial recruited a total of 940 patients (2000 -2008) and compared cisplatin with mitomycin when combined with 5flurouracil CRT and two cycles of maintenance chemotherapy versus no maintenance using a factorial 2x2 design. Patient characterstics: T1/2 52%, T3/4 46%; N+ 32% N0 62%. The loco-regional response to treatment was assessed by clinical examination at 11, 18 and 26 weeks after CRT. Clinical examination was performed every two months for year 1; 3-monthly for year 2; then 6-monthly for years 3-5. CT scans of chest/abdomen/pelvis were performed at 6,12 24 months. Sites of failure were recorded on a case record form (primary site [PS], inguinal [ING], pelvic nodes [PEL], metastatic [METS]. Results: After a median follow up of 5 years, the crude pelvic failure (PF) rate is 18% (163/924). Of the 163 PF, 133 pts (82%) were pelvic only and 30 (18%) had PF + metastasis. 93% of all pelvic recurrences were detected during the first three years (54% yr 1, 26% yr 2 and 13% yr 3). The pattern was similar for PF only and PF + mets (data not shown). Only 46 (4%) of patients had [METS] as the first disease related event. 117/133 (88%) patients with PF only are evaluable for analysis of the pattern of failure., 53% occurred at the primary site (PS) only, 23% were PS + nodal (5% [ING] 13% [PEL] and 5% [ING+PEL], and 25% nodal only (6% [ING],14% [PEL] and 5% [ING+PEL]). Conclusions: The ACT II trial results with mature follow-up demonstrate a low rate of pelvic failure. Intensive follow up to detect potentially salvageable pelvic failure should be restricted to a maximum of three years in future trials as only 7% of relapses occur beyond this time point.

British Journal of Cancer, May 21, 2013

Background: We investigated the feasibility of dose-dense neoadjuvant chemotherapy (NACT) with pa... more Background: We investigated the feasibility of dose-dense neoadjuvant chemotherapy (NACT) with paclitaxel and carboplatin before radical chemoradiation (CRT) and assessed the response rate to such a regimen. Methods: CxII is a single-arm phase II trial of 46 patients, with locally advanced cervical cancer (stage Ib2-IVa). Patients received dose-dense carboplatin (AUC2) and paclitaxel (80 mg m À 2) weekly for six cycles followed by CRT (40 mg m À 2 of weekly cisplatin, 50.4 Gy, 28 fractions plus brachytherapy). The primary end point was response rate 12 weeks post-CRT. Results: Baseline characteristics were: median age at diagnosis 43 years; 72% squamous, 22% adenocarcinoma and 7% adenosquamous histologies; FIGO stage IB2 (11%), II (50%), III (33%), IV (7%). Complete or partial response rate was 70% (95% CI: 54-82) post-NACT and 85% (95% CI: 71-94) post-CRT. The median follow-up was 39.1 months. Overall and progression-free survivals at 3 years were 67% (95% CI: 51-79) and 68% (95% CI: 51-79), respectively. Grade 3/4 toxicities were 20% during NACT (11% haematological, 9% non-haematological) and 52% during CRT (haematological: 41%, non-haematological: 22%). Conclusion: A good response rate is achieved by dose-dense weekly NACT with carboplatin and paclitaxel followed by radical CRT. This treatment regimen is feasible as evidenced by the acceptable toxicity of NACT and by the high compliance to radiotherapy (98%).

Nucleic Acids Research, Mar 15, 1997

The GATA motif is a well known positive cis-regulatory element in vertebrates. In this work we re... more The GATA motif is a well known positive cis-regulatory element in vertebrates. In this work we report experimental evidence for the direct participation of a GATA motif in the expression of the Drosophila antibacterial peptide gene Cecropin A1. Previously we have shown that a κB-like site is necessary for Cecropin A1 gene expression. Here we present evidence that the Drosophila Rel protein which binds to the κB-like site requires an intact GATA site for maximal Dif-mediated transactivation of the Cecropin A1 gene. We show that a Drosophila blood cell line contains factors binding specifically to the GATA motif of the Cecropin A1 gene. The GATA binding activity is likely to include member(s) of the GATA family of transcriptional regulators. We show that the promoters of several inducible insect immune genes possess GATA sites 0-12 base pairs away from κB-like sites in functionally important promoter regions. Clusters of GATA and κB sites are also observed in the promoters of two important mammalian immune genes, namely IL6 and IL3. The consistent proximity of GATA and κB sites appears to be a common theme in the immune gene expression of insects and mammals.

The EMBO Journal, Jul 15, 1999

Insects possess a powerful immune system, which in response to infection leads to a vast producti... more Insects possess a powerful immune system, which in response to infection leads to a vast production of different antimicrobial peptides. The regulatory regions of many immunity genes contain a GATA motif in proximity to a κB motif. Upon infection, Rel proteins enter the nucleus and activate transcription of the immunity genes. High levels of Rel protein-mediated Cecropin A1 expression previously have been shown to require the GATA site along with the κB site. We provide evidence demonstrating that the GATA motif is needed for expression of the Cecropin A1 gene in larval fat body, but is dispensable in adult fat body. A nuclear DNA-binding activity interacts with the Cecropin A1 GATA motif with the same properties as the Drosophila GATA factor Serpent. The GATAbinding activity is recognized by Serpent-specific antibodies, demonstrating their identity. We show that Serpent is nuclear in larval fat body cells and haemocytes both before and after infection. After overexpression, Serpent increases Cecropin A1 transcription in a GATA-dependent manner. We propose that Serpent plays a key role in tissue-specific expression of immunity genes, by priming them for inducible activation by Rel proteins in response to infection.

Variations in the CLL DNA methylome reflect modifications that occur during normal B cell maturat... more Variations in the CLL DNA methylome reflect modifications that occur during normal B cell maturation, along with IGHV mutated (M-CLL) and unmutated CLL (U-CLL), retaining an imprint of the DNA methylation signature of memory (m-CLL) and naive B cells (n-CLL), respectively, with a third intermediate epigenetic subgroup (i-CLL) (1-3). To further test the clinical utility of DNA methylation signatures, we performed the first analysis of patients entering clinical trials; we tested treatment-naive CLL patients [n=605] randomized to CLL4 (chemotherapy, CT) (4), ARCTIC and ADMIRE (both chemo-immunotherapy, CIT) (5, 6). We identified n-, i- and m-CLL in 49.3% (n=299), 32.0% (n=195) and 18.5% (n=112) of our patients, respectively. Fewer m-CLL patients were identified in our study compared to published data reflecting the progressive nature of our cohort, with 80% (n=245/305, P<0.001) of U-CLL cases exhibiting the n-CLL signature (i-CLL: 17% and m-CLL: 3%). For M-CLL cases, 9%, 50% and 41% exhibited the n-, i- and m-CLL epigenetic signature, respectively. 68% (80/117, p<0.001) of cases with del(11q), 77% (41/53, p<0.001) with trisomy 12, and 68% (38/56, p=0.03) with TP53 lesions were n-CLL. Cases with NOTCH1 (p=0.01) and SF3B1 (p=0.02) mutations were also enriched in n-CLL. Next, we investigated the impact of methylation signatures on progression-free (PFS) and overall survival (OS). In CT patients, n-, i- and m-CLL patients exhibited a median PFS of 23, 34 and 35 months, and OS of 63, 66 and 106 months, respectively. n-CLL showed significantly shorter PFS than i-CLL (HR 0.64, p<0.001) and m-CLL (HR 0.52, p<0.001), and had the shortest OS, again compared to i-CLL (HR 0.73, p=0.01) and m-CLL (HR 0.33, p<0.001). Ten-year OS differed according to epigenetic signature (P<0.001) and was reached by only 14% of n-CLL patients. Multivariate Cox proportional analysis, controlling for confounding variables (incl. clinical features, IGHV status, TP53, NOTCH1 and SF3B1) in 278 patients, showed that m-CLL was an independent prognostic factor for OS (HR 0.46, p<0.01). In 247 CIT patients, univariate analysis showed that the i- (HR:0.57, p=0.05) and m-CLL (HR:0.3, p=0.002) subgroups displayed longer PFS. In a multivariate model, including TP53 lesions and IGHV status (239 patients), the m-CLL subgroup retained independent prognostic significance (HR:0.25, p<0.001). In conclusion, we provide important evidence that DNA methylation analysis may aid in the identification of patients destined to demonstrate durable remissions when treated with these agents. References: 1. Kulis, M. et al. Nat Genet 44, 1236-1242 (2012). 2. Queiros, A.C. et al. Leukemia 29, 598-605 (2015). 3. Oakes CC, et al. Nat Genet. 2016 Mar;48(3):253-64. 4. Catovsky, D. et al. Lancet 370, 230-239 (2007). 5. Howard, D.R. et al. Leukemia Nov;31(11):2416-2425 (2017). 6. Munir, T. et al. Leukemia Oct;31(10):2085-2093 (2017). Citation Format: Tomasz K. Wojdacz, Harindra E. Amarasinghe, Matthew JJ Rose-Zerilli, Alice Beattie, Jade Forster, Latha Kadalayil, Stuart Blakemore, Helen Parker, Marta Larrayoz, Ruth Clifford, Zadie Davis, Monica Else, Dena Cohen, Andrew J. Steele, Richard Rosenquist, Andrew Collins, Andrew Pettitt, Peter Hillmen, Christoph Plass, Anna Schuh, Daniel Catovsky, David G. Oscier, Christopher C. Oakes, Jonathan C. Strefford. The clinical importance of DNA methylation signatures in chronic lymphocytic leukemia patients treated with chemo-immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3306.

The New England Journal of Medicine, Feb 14, 2013

This letter provides quality-of-life results from the authors' article in a form that is cons... more This letter provides quality-of-life results from the authors' article in a form that is consistent with the concomitantly published results of another trial. The two studies have consistent results, not only in terms of ablation success rates but also quality-of-life scores.

Lancet Oncology, 2010

Background Between 1990 and 2000, we examined the eff ect of timing of non-platinum chemotherapy ... more Background Between 1990 and 2000, we examined the eff ect of timing of non-platinum chemotherapy when combined with radiotherapy. We aimed to determine whether giving chemotherapy concurrently with radiotherapy or as maintenance therapy, or both, aff ected clinical outcome. Here we report survival and recurrence after 10 years of follow-up. Methods Between Jan 15, 1990, and June 20, 2000, 966 patients were recruited from 34 centres in the UK and two centres from Malta and Turkey. Patients with locally advanced head and neck cancer, and who had not previously undergone surgery, were randomly assigned to one of four groups in a 3:2:2:2 ratio, stratifi ed by centre and chemotherapy regimen: radical radiotherapy alone (n=233); radiotherapy with two courses of chemotherapy given simultaneously on days 1 and 14 of radiotherapy (SIM alone; n=166); or 14 and 28 days after completing radiotherapy (SUB alone, n=160); or both (SIM+SUB; n=154). Chemotherapy was either methotrexate alone, or vincristine, bleomycin, methotrexate, and fl uorouracil. Patients who had previously undergone radical surgery to remove their tumour were only randomised to radiotherapy alone (n=135) or SIM alone (n=118), in a 3:2 ratio. The primary endpoints were overall survival (from randomisation), and event-free survival (EFS; recurrence, new tumour, or death; whichever occurred fi rst) among patients who were disease-free 6 months after randomisation. Analyses were by intention to treat. This trial is registered at www.Clinicaltrials.gov, number NCT00002476. Findings All 966 patients were included in the analyses. Among patients who did not undergo surgery, the median overall survival was 2•6 years (99% CI 1•9-4•2) in the radiotherapy alone group, 4•7 (2•6-7•8) years in the SIM alone group, 2•3 (1•6-3•5) years in the SUB alone group, and 2•7 (1•6-4•7) years in the SIM+SUB group (p=0•10). The corresponding median EFS were 1•0 (0•7-1•4), 2•2 (1•1-6•0), 1•0 (0•6-1•5), and 1•0 (0•6-2•0) years (p=0•005), respectively. For every 100 patients given SIM alone, there are 11 fewer EFS events (99% CI 1-21), compared with 100 given radiotherapy, 10 years after treatment. Among the patients who had previously undergone surgery, median overall survival was 5•0 (99% CI 1•8-8•0) and 4•6 (2•2-7•6) years in the radiotherapy alone and SIM alone groups (p=0•70), respectively, with corresponding median EFS of 3•7 (99% CI 1•1-5•9) and 3•0 (1•2-5•6) years (p=0•85), respectively. The percentage of patients who had a signifi cant toxicity during treatment were: 11% (radiotherapy alone, n=25), 28% (SIM alone, n=47), 12% (SUB alone, n=19), and 36% (SIM+SUB, n=55) among patients without previous surgery; and 9% (radiotherapy alone, n=12) and 20% (SIM alone, n=24) among those who had undergone previous surgery. The most common toxicity during treatment was mucositis. The percentage of patients who had a signifi cant toxicity at least 6 months after randomisation were: 6% (radiotherapy alone, n=13), 6% (SIM alone, n=10), 4% (SUB alone, n=7), and 6% (SIM+SUB, n=9) among patients who had no previous surgery; and 7% (radiotherapy alone, n=10) and 11% (SIM alone, n=13) among those who had undergone previous surgery. The most common toxicity 6 months after treatment was xerostomia, but this occurred in 3% or less of patients in each group. Interpretation Concurrent non-platinum chemoradiotherapy reduces recurrences, new tumours, and deaths in patients who have not undergone previous surgery, even 10 years after starting treatment. Chemotherapy given after radiotherapy (with or without concurrent chemotherapy) is ineff ective. Patients who have undergone previous surgery for head and neck cancer do not benefi t from non-platinum chemotherapy.

Annals of Allergy Asthma & Immunology, Feb 1, 2023