scholarly journals Addressing the statistical analysis dilemma that exists when analyzing clinical trial results with full efficacy using the Kaplan Meier survival analysis method

2021 ◽  
Vol 2 ◽  
Author(s):  
Pimnara Peerawaranun ◽  
Rob W. van der Pluijm ◽  
Mavuto Mukaka
Keyword(s):  
Missing Data ◽  
Confidence Intervals ◽  
Treatment Success ◽  
Exact Test ◽  
Efficacy Trials ◽  
Kaplan Meier ◽  
Clinical Trial Results ◽  
M Estimates ◽  
Cure Rates ◽  
Main Strategy

Abstract The use of a Kaplan–Meier (K–M) survival time approach is generally considered appropriate to report antimalarial efficacy trials. However, when a treatment arm has 100% efficacy, confidence intervals may not be computed. Furthermore, methods that use probability rules to handle missing data for instance by multiple imputation, encounter perfect prediction problem when a treatment arm has full efficacy, in which case all imputed values are either treatment success or all imputed values are failures. The use of a survival K–M method addresses this imputation problem in estimating the efficacy estimates also referred to as cure rates. We discuss the statistical challenges and propose a potential way forward. The proposed approach includes the use of K–M estimates as the main measure of efficacy. Confidence intervals could be computed using the binomial exact method. p-Values for comparison of difference in efficacy between treatments can be estimated using Fisher’s exact test. We emphasize that when efficacy rates are not 100% in both groups, the K–M approach remains the main strategy of analysis considering its statistical robustness in handling missing data and confidence intervals can be computed under such scenarios.

scholarly journals One-year outcomes of microhook trabeculotomy versus suture trabeculotomy ab interno

2021 ◽  
Author(s):  
Hiroshi Yokoyama ◽  
Masashi Takata ◽  
Fumi Gomi
Keyword(s):  
Survival Analysis ◽  
Clinical Success ◽  
Treatment Success ◽  
Medication Use ◽  
Glaucoma Surgery ◽  
Success Rates ◽  
Kaplan Meier ◽  
One Year ◽  
Ab Interno

Abstract Purpose To compare clinical success rates and reductions in intraocular pressure (IOP) and IOP-lowering medication use following suture trabeculotomy ab interno (S group) or microhook trabeculotomy (μ group). Methods This retrospective review collected data from S (n = 104, 122 eyes) and μ (n = 42, 47 eyes) groups who underwent treatment between June 1, 2016, and October 31, 2019, and had 12-month follow-up data including IOP, glaucoma medications, complications, and additional IOP-lowering procedures. The Kaplan–Meier survival analysis was used to evaluate treatment success rates defined as normal IOP (> 5 to ≤ 18 mm Hg), ≥ 20% reduction of IOP from baseline at two consecutive visits, and no further glaucoma surgery. Results Schlemm’s canal opening was longer in the S group than in the μ group (P < 0.0001). The Kaplan–Meier survival analysis of all eyes showed cumulative clinical success rates in S and µ groups were 71.1% and 61.7% (P = 0.230). The Kaplan–Meier survival analysis of eyes with preoperative IOP ≥ 21 mmHg showed cumulative clinical success rates in S and μ groups were 80.4% and 60.0% (P = 0.0192). There were no significant differences in postoperative IOP at 1, 3, and 6 months (S group, 14.9 ± 5.6, 14.6 ± 4.5, 14.6 ± 3.9 mmHg; μ group, 15.8 ± 5.9, 15.2 ± 4.4, 14.7 ± 3.7 mmHg; P = 0.364, 0.443, 0.823), but postoperative IOP was significantly lower in the S group at 12 months (S group, 14.1 ± 3.1 mmHg; μ group, 15.6 ± 4.1 mmHg; P = 0.0361). There were no significant differences in postoperative numbers of glaucoma medications at 1, 3, 6, and 12 months (S group, 1.8 ± 1.6, 1.8 ± 1.5, 2.0 ± 1.6, 1.8 ± 1.5; μ group, 2.0 ± 1.6, 2.0 ± 1.6, 2.1 ± 1.6, 2.2 ± 1.7; P = 0.699, 0.420, 0.737, 0.198). Conclusion S and µ group eyes achieved IOP reduction, but μ group eyes had lower clinical success rates among patients with high preoperative IOP at 12 months.

Lightbulb technique for the treatment of osteonecrosis of the femoral head

2017 ◽  
Vol 28 (3) ◽  
pp. 272-277 ◽  
Author(s):  
Cemil Yildiz ◽  
Yusuf Erdem ◽  
Kenan Koca
Keyword(s):  
Femoral Head ◽  
Disease Progression ◽  
Bone Grafting ◽  
Treatment Effectiveness ◽  
Treatment Success ◽  
Total Hip ◽  
Kaplan Meier ◽  
Grafting Technique ◽  
Stage 4 ◽  
Stage 1

Introduction: The aim of this study was to report the clinical and radiological outcomes for 21 patients (28 hips) treated for osteonecrosis of the femoral head using the lightbulb technique, a nonvascularised bone grafting technique. Methods: The study group included 14 men and 7 women, with a mean age of 33.2 (range 22-50) years, presenting with avascular necrosis of the femoral head of stage 4a or earlier, according to the Steinberg classification. Patients were treated using the nonvascularised lightbulb bone grafting technique. The primary clinical outcome was the Harris Hip Scores (HHS), while primary outcomes of treatment effectiveness and disease progression were based on radiographic evidence of disease progression and the need for total hip replacement. The rate of treatment success and failure was evaluated using the Kaplan-Meier survival analysis. Results: The mean HHS increased from 52.66 to 74.33 after treatment, with excellent-to-good outcomes obtained in 21 (75%) of the cases. Fair-to-poor results were obtained in 7 (25%) of the cases, with total hip arthroplasty subsequently required in 5 of these cases. The radiological failure rate was 50% among cases treated in Steinberg stage 1 (1/2), 42% in stage 3 (5/12), and 100% in stage 4 (2/2). Conclusions: The lightbulb technique can provide a clinically acceptable rate of successful treatment of osteonecrosis of the femoral head when used in the early stages of the disease, prior to collapse of the femoral head.

Tolerance, survival and adherence to treatment with methotrexate in patients with rheumatoid arthritis

2019 ◽  
pp. 13-17
Author(s):  
J.M. Sevillano Gutierrez ◽  
D. Capelusnik ◽  
E.E. Schneeberger ◽  
G. Citera
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Descriptive Statistics ◽  
P Value ◽  
Multiple Logistic Regression ◽  
Adherence To Treatment ◽  
Exact Test ◽  
Cumulative Survival ◽  
Kaplan Meier ◽  
Chi2 Test

Background: Methotrexate (MTX) is the most frequently used medication in patients with Rheumatoid Arthritis (RA). However, several authors have questioned its success due to the presence of adverse events and the lack of adherence. Objectives: to determine cumulative survival of MTX, frequency and type of adverse events and causes of discontinuation in patients with RA. Methods: consecutive patients 18 years and older with a diagnosis of RA (ACR/EULAR 2010 criteria), who had begun treatment with MTX during their disease were included. Sociodemographic, clinical and therapeutic data were collected. Date of initiation and suspension of MTX, route of administration, concomitant treatments, consumption of coffee and tobacco, presence of adverse events (AE) were all consigned. Adherence was evaluated using the Compliance Questionnaire Rheumatology questionnaire 5-item summary version (CQR5). Statistical analysis: descriptive statistics. Chi2 test or Fisher’s exact test; Survival of treatment by Kaplan-Meier and log Rank. Multiple logistic regression. A p value <0.05 was considered significant.

Evaluation of different MET genotypes as biomarkers for immunotherapy outcomes in NSCLC patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21032-e21032
Author(s):  
Xuanzong Li ◽  
Linlin Wang
Keyword(s):  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Rank Test ◽  
Wild Type ◽  
Exact Test ◽  
Entire Cohort ◽  
Kaplan Meier ◽  
Tumor Mutational Burden ◽  
The Difference ◽  
Nsclc Patients

e21032 Background: Previous studies suggested that MET exon 14 ( METex14) mutation regarding as a distinct subset was sensitive to MET-inhibitors, but poorly response to immunotherapy. Conversly, MET non-exon-14 (non-ex14) mutations including those undetermined functions and affecting the kinase or extracellular domains were found to be associated with the resistance to MET-inhibitors. However, therapeutic strategies for MET-non-ex14 mutant cancer are still largely unknown, and the relationship between MET-non-ex14 mutations and the efficacy of immune checkpoint inhibitors (ICIs) has never been reported. Using two public ICIs-treated cohorts, we aimed to assess the role of MET mutations including both METex14 and MET-non-ex14 mutations in NSCLC patients undergoing ICIs therapy. Methods: A total of 385 ICIs-treated NSCLC patients were enrolled to our study. MET mutations were defined as any nonsynonymous mutations, and we divided them into METex14 and MET-non-ex14 mutation subsets according to the mutated-position on MET. Kruskal-Wallis test was used to analyze the difference of tumor mutational burden (TMB) score, and the Fisher’s exact test was applied to compare the rates of durable clinical benefit (DCB). Log-rank test was used to analyze the differences between Kaplan-Meier survival curves. Results: In the entire cohort, we found that 17 patients (17/385, 4.4%) had MET mutations, most of which were pure METex14 mutations (10/17, 58.8%). The median TMB of patients in the entire NSCLC cohort was 6.89 mut/Mb. MET-non-ex14 mutant patients (7/385, 1.8%) possessed a significantly higher TMB than METex14-mutant (10/385, 2.6%) and MET wild-type (368/385, 95.6%) sub-cohorts, respectively (median TMB, 17.92 mut/Mb versus 4.17 mut/Mb, p = 0.008; 17.92 mut/Mb versus 6.96 mut/Mb, p = 0.01, respectively). DCB was more common in patients harbored MET-non-ex14 mutations than patients with METex14 mutations and MET wild-type (66.7% versus 14.3%, p = 0.103; 66.7% versus 29.9%, p = 0.075, respectively). We found that patients with MET-non-ex14 mutations had a numerically longer progression free survival (PFS) than those with METex14 mutations and MET wild-type (p = 0.169). Moreover, the PFS was significantly longer in MET-non-ex14-mutant subgroup than patients with METex14 mutations (median PFS, 9.1 versus 2.1 months, p = 0.025). Correspondingly, the overall survival (OS) was significantly longer in MET-non-ex14-mutant subgroup than their wild-type counterparts (median OS, not reached versus 11 months, p = 0.039). Additionally, patients with MET-non-ex14 mutations exhibited relatively better OS versus METex14-mutant patients (median OS, not reached versus 18 months, p = 0.175). Conclusions: MET-non-ex14 mutations were associated with higher TMB, improved DCB rate, and could act as a favorable prognostic biomarker in ICIs-treated NSCLC patients.

scholarly journals Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda

2020 ◽  
Vol 26 (10) ◽  
pp. 1602-1608 ◽  
Author(s):  
Aline Uwimana ◽  
Eric Legrand ◽  
Barbara H. Stokes ◽  
Jean-Louis Mangala Ndikumana ◽  
Marian Warsame ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Plasmodium Falciparum ◽  
Gene Editing ◽  
De Novo ◽  
Artemisinin Resistance ◽  
Clonal Expansion ◽  
Efficacy Trials ◽  
Cure Rates ◽  
Antimalarial Chemotherapy

Abstract Artemisinin resistance (delayed P. falciparum clearance following artemisinin-based combination therapy), is widespread across Southeast Asia but to date has not been reported in Africa1–4. Here we genotyped the P. falciparum K13 (Pfkelch13) propeller domain, mutations in which can mediate artemisinin resistance5,6, in pretreatment samples collected from recent dihydroarteminisin-piperaquine and artemether-lumefantrine efficacy trials in Rwanda7. While cure rates were >95% in both treatment arms, the Pfkelch13 R561H mutation was identified in 19 of 257 (7.4%) patients at Masaka. Phylogenetic analysis revealed the expansion of an indigenous R561H lineage. Gene editing confirmed that this mutation can drive artemisinin resistance in vitro. This study provides evidence for the de novo emergence of Pfkelch13-mediated artemisinin resistance in Rwanda, potentially compromising the continued success of antimalarial chemotherapy in Africa.

scholarly journals A descriptive report of outcomes of primary mucinous ovarian cancer patients receiving either an adjuvant gynecologic or gastrointestinal chemotherapy regimen

2019 ◽  
Vol 29 (5) ◽  
pp. 904-909
Author(s):  
Brooke A Schlappe ◽  
Qin C Zhou ◽  
Roisin O'Cearbhaill ◽  
Alexia Iasonos ◽  
Robert A Soslow ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Progression Free Survival ◽  
Categorical Variables ◽  
Continuous Variables ◽  
Free Survival ◽  
Exact Test ◽  
Clinical Criteria ◽  
Kaplan Meier

ObjectiveWe described progression-free survival and overall survival in patients with primary mucinous ovarian cancer receiving adjuvant gynecologic versus gastrointestinal chemotherapy regimens.MethodsWe identified all primary mucinous ovarian cancer patients receiving adjuvant gynecologic or gastrointestinal chemotherapy regimens at a single institution from 1994 to 2016. Gynecologic pathologists using strict pathologic/clinical criteria determined diagnosis. Adjuvant therapy was coded as gynecologic or gastrointestinal based on standard agents and schedules. Clinical/pathologic/treatment characteristics were recorded. Wilcoxon rank-sum test was used for continuous variables, and Fisher’s exact test for categorical variables. Progression-free and overall survival were calculated using the Kaplan-Meier method, applying landmark analysis.ResultsOf 62 patients identified, 21 received adjuvant chemotherapy: 12 gynecologic, 9 gastrointestinal. Median age (in years) at diagnosis: 58 (range 25–68) gynecologic cohort, 38 (range 32–68) gastrointestinal cohort (p=0.13). Median body mass index at first post-operative visit: 25 kg/m2(range 18–31) gynecologic cohort, 23 kg/m2(range 18–31) gastrointestinal cohort (p=0.23). History of smoking: 6/12 (50%) gynecologic cohort, 3/9 (33%) gastrointestinal cohort (p=0.66). Stage distribution in gynecologic and gastrointestinal cohorts, respectively: stage I: 9/12 (75%) and 3/9 (33%); stage II: 2/12 (17%) and 1/9 (11%); stage III: 1/12 (8%) and 5/9 (56%) (p=0.06). Grade distribution in gynecologic and gastrointestinal cohorts, respectively: grade 1: 8/12 (67%) and 1/9 (13%); grade 2/3: 4/12 (33%) and 7/9 (88%) (p=0.03). Three-year progression-free survival: 90.9% (95% CI 50.8% to 98.7 %) gynecologic, 53.3% (95% CI 17.7% to 79.6%) gastrointestinal. Three-year overall survival: 90.9% (95% CI 50.8% to 98.7%) gynecologic, 76.2% (95% CI 33.2% to 93.5%) gastrointestinal.ConclusionOngoing international collaborative research may further define associations between chemotherapy regimens and survival.

Post-That Washing Prior to Transplantation of Umbilical Cord Blood (UCB) That Were Depleted of Plasma but Not of Red Blood Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5229-5229
Author(s):  
Robert Chow ◽  
Patrick Tan ◽  
Tang-Her Jaing ◽  
Joseph Rosenthal ◽  
Auayporn Nademanee ◽  
...  
Keyword(s):  
Median Time ◽  
Relapse Rate ◽  
Survival Data ◽  
Negative Impact ◽  
Chronic Gvhd ◽  
Cell Recovery ◽  
Hematopoietic Stem ◽  
Kaplan Meier ◽  
M Estimate ◽  
M Estimates

Abstract Washing after thawing of frozen UCB used for hematopoietic stem cell transplantation (HSCT) is widely practiced for the purpose of removal of the cryoprotectant DMSO and free hemoglobin from lysed red cells. An updated retrospective audited analysis was performed on the outcomes of 208 PD UCB used in 186 patients with known thaw conditions that have engraftment and/or survival data −106 washed (W) and 80 non-washed (NW). When the DMSO dose was kept under the recommended 1 g per kg of recipient weight, the only severe adverse reaction was a seizure and encephalopathy following infusion of a NW PD UCB that resolved without any sequelae. Total nucleated cell recovery after thawing as reported by transplant centers was higher for NW (median 89% vs. 75%). The Kaplan-Meier estimate of 3-month neutrophil (ANC500) engraftment were 91±4% for NW versus 88±4% for W with median time to neutrophil of 21 versus 24 days (p = 0.02). The K-M estimate for 6-month platelet 20K engraftment were 86±6% for NW and 78±5% for W with median time to engraftment at 46 days for NW and 55 days for W (p = 0.002). Acute grade III–IV GvHD were similar at 12% (NW) and 13% (W), but extensive chronic GvHD were 4% (NW) and 19% (W). 1-year TRM were 25±5% for NW and 34±5% for W (p=0.75), with relapse rate at 16±5% for NW and 28±5% for W (p=0.09). K-M estimates of 1-year OS were 63±6% versus 53±5% (p = 0.54), and for 1-year DFS were 62±6% versus 48±5% (p = 0.23) for NW and W respectively. To our knowledge, this was the largest transplant outcome study comparing no post-thaw wash versus wash for UCB, though the conclusions are confined to PD CBU. No clear benefits of post-thaw washing were seen for PD UCB. HSCT with NW PD UCB was at least as efficacious as that using W PD UCB with respect to GvHD, TRM, relapse rate, 1-year OS and DFS. Moreover, washing may have a negative impact on neutrophil and platelet engraftment of PD UCB.

Specific Chromosomal IG Translocations Have Different Prognosis In Chronic Lymphocytic Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 582-582
Author(s):  
Florence Nguyen-Khac ◽  
CLaude Lesty ◽  
Elise Chapiro ◽  
Aurore Grelier ◽  
Isabelle Luquet ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Sex Ratio ◽  
Conflicts Of Interest ◽  
Lymphocytic Leukemia ◽  
Rank Test ◽  
Exact Test ◽  
Kaplan Meier ◽  
Trisomy 12 ◽  
Binet Stage ◽  
The Individual

Abstract Abstract 582 Chromosomal translocations (t) are usually analyzed as one group, and are associated with poor prognosis in chronic lymphocytic leukemia (CLL). Translocations involving immunoglobulin (IG) genes are recurrent, but uncommon (< 5%) in CLL. The two most frequent IG-partners are BCL2 (18q21) and BCL3 (19q13). On the behalf of the Groupe Francophone de Cytogenetique Hematologique (GFCH), we report an extensive analysis of 75 t(14;18)-CLLs, and a comparison to our previously published series of 29 t(14;19)-CLLs (Chapiro et al, Leukemia 2008). The 75 t(14;18)-CLLs or variant BCL2-t have been collected between 1985 and 2009. The morphological and immunological reviews were performed by KM, CS, and HM-B. All karyotypes were reviewed by the GFCH. Fluorescence in situ hybridization analyses were performed to detect IG and BCL2 rearrangements, trisomy 12, and deletions of 11q22 (ATM), 17p13 (TP53), 6q21, 13q14 (D13S319). IGHV mutation analyses were performed by referring laboratories. Statistical analyses were carried out using the Fisher's exact test, and continuous data using the Mann-Whitney test. Overall survival (OS) and treatment free survival (TFS) calculated from diagnosis were estimated using the Kaplan-Meier method, and the statistic significance was determined using log-rank test. Among BCL2-CLL, the sex ratio was 57M/18F, the median age at diagnosis was 66 years; of 68 patients with available data, 63 (93%) presented with Binet stage A; median lymphocytosis was 14.6×109/l. There were 47/75 (63%) “classical” CLL and 28/75 (37%) “atypical” CLL, with more than 10% of lymphoplasmacytoid cells and/or large cells. All tested cases (58/58) were CD10-, 69/73 (94%) were CD5+, and 44/63 (70%) were CD38-; 57/68 (84%) had a Matutes score > 4, 7/68 (10%) a score = 3, 4/68 (6%) a score < 3. We observed 62 t(14;18) and 13 variant translocations [11 t(18;22), 2 t(2;18)]. The karyotype was complex (> 3 abnormalities) in 15/74 (20%) cases, and the BCL2-t was isolated in 25/74 (34%) cases. There were 33/75 (44%) tri12, 32/68 (47%) del13q14, 1/72 (1%) delTP53, 0/72 (0%) delATM, 0/59 (0%) del6q21. Of 42 analyzed cases, 33 (78%) were mutated. Finally, the median time from diagnosis to first therapy was 24 months (m). Comparisons with the BCL3-CLL showed no difference in sex ratio, age, and Binet stages. The lymphocytosis was lower in BCL2-CLL (14.6 vs 24.4 x109/l, p<0.008), and splenomegaly was less frequent (3/61 (5%) vs 13/28 (46%), p<0.0001). There were more “classical” morphologies in BCL2-CLL group (63% vs 9/29 (31%), p<0.005), more Matutes score > 4 (84% vs 5/20 (25%), p<0.001), and more CD38- (70% vs 1/5 (20%), p<0.05). BCL2-t were more frequently single (35% vs 1/28 (3%), p<0.0008). There were less complex karyotypes (20% vs 13/28 (46%), p<0.02), more del13q14 (47% vs 4/27 (15%), p<0.005), and less tri12 (44% vs 20/29 (69%), p<0.03), del6q (0% vs 5/25 (20%), p<0.002) and delTP53 (1% vs 4/23 (17%), p<0.02) in BCL2-CLLs. The IGHV status of BCL2-CLLs was more frequently mutated (78% vs 2/20 (10%), p<0.0001). Finally, the TFS interval was longer in BCL2-CLLs (p<0.0001, median 48 vs 1.2 m,); and the median OS was longer (not reached with 75% alive at 204 m) (p<0.0001). Comparison to common CLL showed that BCL2-CLLs had more tri12 (p<0.00001), and lacked delATM (p<0.0001) and del6q (p<0.05). The majority were CD38-, and mutated (p<0.0001). Finally, even if the median TFS was 48m, the median OS was more than 204m, which is longer than the median OS of the prognostically most favorable subgroup reported by Döhner et al (group with isolated del13q, 133m) (Döhner et al, N Eng J Med, 2000). The presence of BCL2-t remains a favorable marker even in patients who also exhibit markers of intermediate prognosis such as tri12. Compared to BCL3-CLLs, BCL2-CLLs have a much less aggressive behavior, indicating that distinguishing the individual translocations and the cytogenetic partners would allow a better patients' stratification. Disclosures: No relevant conflicts of interest to declare.

Promoter hypermethylation of GPX3 as a predictor for chemoresistance and survival in head and neck cancer patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6027-6027 ◽  
Author(s):  
Z. Guo ◽  
Z. Chen ◽  
Z. Yang ◽  
L. Schumaker ◽  
K. J. Cullen
Keyword(s):  
Head And Neck Cancer ◽  
Survival Analysis ◽  
Relative Risk ◽  
Head And Neck ◽  
Cancer Cells ◽  
Cell Lines ◽  
Neck Cancer ◽  
Promoter Hypermethylation ◽  
Exact Test ◽  
Kaplan Meier

6027 Background: Resistance of cancer cells to cisplatin and its analogues is the major limitation in clinical application of cisplatin-based chemotherapy. The mechanisms by which cancer cells develop resistance to the drugs are still unclear, and there is no way currently to predict the drug resistance of individual tumors. By genome-wide scanning of hypermethylated genes on head and neck cancer cells, we identified glutathione peroxidase 3 (GPX3) as one of the strong candidates whose promoter hypermethylation may be associated with head and neck chemoresistance. In this study, we investigated the potential predictive value of GPX3 methylation for head and neck cancer chemoresistance and patient prognosis. Methods: Promoter methylation and expression of GPX3 gene in head and neck cancer cell lines were examined by plasmid cloning, bisulfite DNA sequencing, reverse transcription-PCR and Western blot. GPX3 methylation in primary cancer tissues was assessed by real-time methylation-specific PCR (MSP). Forty-six head and neck cancer cases, for which chemotherapy response and survival were known, were selected for analysis. Correlation of GPX3 methylation and chemoresistance was tested using two-sided Fisher’s Exact Test and its prediction for patient survival was assessed using Kaplan-Meier survival analysis. Results: Loss of GPX3 expression was observed in 4 of 8 head and neck cancer cell lines and was consistent with cisplatin resistance. Demethylating treatment of the cell lines negative for GPX3 expression significantly restored its expression. Bisulfite DNA sequencing showed that the 5’ flanking promoter region of GPX3 was heavily hypermethylated in all cell lines with expression-silencing of the gene. In the 46 head and neck cancer cases analyzed by MSP, 15 of 23 non-responding cases (65%) showed GPX3 methylation, while 4 of 23 complete and partial response cases (17%) contained low levels of GPX3 methylation (Relative Risk 3.343, two sided Fisher’s exact test, P=0.002). Kaplan-Meier survival analysis showed a relative risk of death of 1.942 in patients with GPX3 methylation. Conclusions: Our findings suggest that GPX3 methylation is a strong candidate predictor for chemoresistance and prognosis of head and neck cancer patients. No significant financial relationships to disclose.

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