Xiaoduan Weng

HPV Prevalence and Prognostic Value in a Prospective Cohort of 255 Patients with Locally Advanced HNSCC: A Single-Centre Experience.

Background. HPV is a positive prognostic factor in HNSCC. We studied the prevalence and prognostic impact of HPV on survival parameters and treatment toxicity in patients with locally advanced HNSCC treated with concomitant chemoradiation therapy. Methods. Data on efficacy and toxicity were available for 560 patients. HPV was detected by PCR. Analysis was performed using Kaplan-Meier survival curves, Fishers test for categorical data, and log-rank statistics for failure times. Results. Median follow-up was 4.7 years. DNA extraction was successful in 255 cases. HPV prevalence was 68.6%, and 53.3% for HPV 16. For HPV+ and HPV−, median LRC was 8.9 and 2.2 years (P = 0.0002), median DFS was 8.9 and 2.1 years (P = 0.0014), and median OS was 8.9 and 3.1 years (P = 0.0002). Survival was different based on HPV genotype, stage, treatment period, and chemotherapy regimen. COX adjusted analysis for T, N, age, and treatment remained significant (P = 0.004). Conclusions. Oropharyngeal cancer is increasingly linked to HPV. This study confirms that HPV status is associated with improved prognosis among H&N cancer patients receiving CRT and should be a stratification factor for clinical trials including H&N cases. Toxicity of CRT is not modified for the HPV population.

Prevalence of K-RAS Codons 12 and 13 Mutations in Locally Advanced Head and Neck Squamous Cell Carcinoma and Impact on Clinical Outcomes

Background. RAS gene mutations have an impact on treatment response and overall prognosis for certain types of cancer. Objectives. To determine the prevalence and impact of K-RAS codons 12 and 13 mutations in patients with locally advanced HNSCC treated with primary or adjuvant chemo-radiation. Methods. 428 consecutive patients were treated with chemo-radiation therapy and followed for a median of 37 months. From these, 199 paraffin embedded biopsy or surgical specimens were retrieved. DNA was isolated and analyzed for K-RAS mutational status. Results. DNA extraction was successful in 197 samples. Of the 197 specimens, 3.5% presented K-RAS codon 12 mutations. For mutated cases and non-mutated cases, complete initial response to chemoradiation therapy was 71 and 73% (P = 0.32). LRC was respectively 32 and 83% (P = 0.03), DFS was 27 and 68% (P = 0.12), distant metastasis-free survival was 100 and 81% (P = 0.30) and OS was 57 and 65% (P = 0.14) at three years. K-Ras codon 13 analysis revealed no mutation. Conclusion. K-RAS codon 12 mutational status, although not associated with a difference in response rate, may influence the failure pattern and the type of therapy offered to patients with HNSCC. Our study did not reveal any mutation of K-RAS codon 13.

Prevalence of α-Globin Gene Deletions Among Patients with Unexplained Microcytosis in a North-American Population

Increasing multi-ethnicity is likely to make α-thalassemia (α-thal) more prevalent in Western metropolitan areas. Multiplex polymerase chain reaction (m-PCR) allows rapid and precise identification of most of α-thal carriers. With this method, we sought to determine the prevalence of α-thal and the corresponding genotype, among all non repetitive consecutive blood samples that had an unexplained microcytosis. These specimens had been sent to the hematology laboratory for a blood count analysis, found to be microcytic, and secondarily tested for ferritin level and hemoglobin (Hb) high performance liquid chromatography (HPLC) profile. Five hundred and sixteen microcytic blood samples were evaluated and 197 samples with normal ferritin and Hb HPLC were studied by m-PCR. Among 196 interpretable PCRs, 48 α-thal cases (24.5%) were identified: 28 with a single α-globin gene deletion and 20 with two α-globin gene deletions. Of these 20 cases, six showed two deletions in cis. None of the erythrocytic parameters studied predicted the presence of α-thal deletions. We conclude that a significant proportion (24.5%) of blood counts with microcytosis not explained by an iron deficiency, an inflammatory state or an abnormal Hb on HPLC, are caused by an α-globin gene deletion. The pertinence of genetic counseling for α-thal based on molecular diagnosis should be evaluated more formally in urban centers where this genetic condition is likely to have an increasing prevalence and clinical relevance.

Severe agranulocytosis in a patient with metastatic non-small-cell lung cancer treated with nivolumab.

Immune checkpoint inhibitors are novel agents in the process of revolutionising cancer care. These agents have become a very appealing therapeutic alternative since they are much better tolerated than cytotoxic therapy, due to their relatively favorable toxicity profile. However, adverse events associated with these agents usually involve the immune system and can have serious implications jeopardising survival. Herein we report the first case of immune-mediated agranulocytosis due to Nivolumab therapy. The patient suffered from Staphylococcus infection during her agranulocytosis which only responded to high dose corticosteroid therapy.

Mutations in NSCLC and their link with lung cancer-associated thrombosis: A case-control study☆

INTRODUCTION The association of venous thromboembolic events (VTE) and lung cancer is highly prevalent. Additionally, the occurrence of a VTE with cancer has been associated with a worse prognosis and a poor quality of life. Underlying cancer biological features such as tumour mutations may contribute to VTE risk and cancer prognosis. Since preclinical data suggest a link between thrombosis and KRAS mutations in tumours, we aimed to validate this association in a patient registry cohort. METHODS A retrospective case control study was performed using the CHUM NSCLC registry. Cases had VTE occurring 6months previous to or after a diagnosis of NSCLC. Diagnosis of VTE (venous thrombosis, pulmonary embolism, and migratory superficial thrombophlebitis) was confirmed by a review of the imaging reports. Controls were patients with NSCLC without thrombosis matched for age and stage (I-IIIA/IIIB-IV). Exclusion criteria included insufficient tissue for KRAS/EGFR mutation analysis or insufficient clinical information. RESULTS Between Jan 2000 and Dec 2009 a total of 57 cases with VTE and 102 controls without VTE were included. The OR for thrombosis in KRAS and EGFR mutated NSCLC patients are respectively 2.67 (1.12-6.42; p=0.014) and 0.99 (0.27-3.48; p=0.99). CONCLUSIONS KRAS mutation is associated with an increased risk of VTE in this NSCLC cohort. These findings are consistent with preclinical studies. Prospective data on VTE rates from clinical trials with molecularly defined NSCLC are needed to confirm these findings.

Treatment with hydroxyurea in a patient compound heterozygote for a high oxygen affinity hemoglobin and β‐thalassemia minor

Compound heterozygotes for β-thalassemia and high oxygen affinity hemoglobin (Hb) have been documented, but experience in the management of such rare cases is minimal. Although hydroxyurea (HU) has never been used in a heterozygote with high oxygen affinity Hb and β-thalassemia, we hypothesized that it would decrease erythrocytosis through a lowered production of abnormal cells and increase of P 50 by induction of fetal hemoglobin (HbF). We present the case of a patient with compound high oxygen affinity Hb mutation with β-thalassemia. PCR analysis revealed combined Hb Regina and IVS1-110 G/A mutations. Treatment with HU caused a decrease in Ht (61.1% to 38.6%) and erythrocyte volume (74.87 mUkg to 40.65 mUkg), as well as an increase in P 50 (6 mmHg to 10 mmHg ) and HbF level (3.6% to 29.8%) at 12-month follow-up. Effects of HU on 2,3 DPG and HbNO levels did not appear to be predictable. Corroboration with other cases is needed to establish solid evidence on the clinical efficacy of HU in this population.

A New Insertion Mutation in the β-Globin Gene [Codons 45/46 (+A)] Resulting in a β-Thalassemia Minor Phenotype

The β-globin gene of 306 newly diagnosed β-thalassemia (thal) minor patients were sequenced. Analysis revealed that only one amongst all the identified mutations had not been previously reported. This new mutation, causing a β+-thal minor phenotype, was found in a patient of Arabic origin. The insertion frameshift mutation (+A) between codons 45 and 46 [codons 45/46 (+A)] results in a premature termination signal at codon 52. No truncated β-globin or abnormal hemoglobin (Hb) was identified.

Case report: Efficacy of ponatinib in a case of chronic myeloid leukemia with a complicated clonal evolution including a myelodysplastic syndrome

Abstract Chronic myeloid leukemia (CML) is characterised by the presence of the Philadelphia chromosome (Ph), which results in the production of the constitutively active tyrosine kinase BCR-ABL1, with tyrosine kinase inhibitors (TKI)