Non-small cell lung cancer-smokers or non-smokers, does it matter?

Besides epidermal growth factor receptor (EGFR) gene mutations, clinical factors such as smoking status have been identified as predictors for survival for NSCLC patients treated with EGFR-tyrosine kinase inhibitors (TKI). However, the biological screening for EGFR gene mutations is not routinely available everywhere. Therefore, the question arises if the decision to treat patients with EGFR-TKI should be based on clinical factors, and in particular smoking status, alone. We illustrate the difficulties faced by clinicians with the case of a 56-year-old man with stage IV lung adenocarcinoma and a smoking history of 30-pack-year. This patient received erlotinib first-line after its enrolment in a clinical trial. After 4 months, he presented with a dramatic clinical and radiological response. The biological analysis of the tumour revealed an EGFR exon 19 deletion. This report emphasizes that smoking status alone appears inappropriate in selecting patients for EGFR-TKI treatment. In addition, the relatively high number of (ex-)smokers retrieved from prospective studies on NSCLC patients with tumours showing an EGFR mutation should be emphasized, as it represents up to 30% of patients. Therefore, a biological rather than a clinical selection for patients' eligibility for EGFR-TKI appears mandatory.     

A phase II trial of CHOP chemotherapy followed by yttrium 90 ibritumomab tiuxetan (Zevalin) for previously untreated elderly diffuse large B-cell lymphoma patients

Background: A prospective, single-arm, open-label, nonrandomizedphase II combination chemotherapy with cyclophosphamide, doxorubicin,vincristine, and prednisone (CHOP) plus radioimmunotherapy trialwas conducted to evaluate the efficacy and safety in untreatedelderly diffuse large B-cell lymphoma (DLBCL) patients. Patients and methods: From February 2005 to April 2006, in ourinstitute we treated 20 eligible elderly (age 60 years) patientswith previously untreated DLBCL using a novel regimen consistingof six cycles of CHOP chemotherapy followed 6–10 weekslater by ⁹⁰Y ibritumomab tiuxetan. Results: The overall response rate to the entire treatment regimenwas 100%, including 95% complete remission (CR) and 5% partialremission. Four (80%) of the five patients who achieved lessthan a CR with CHOP improved their remission status after radioimmunotherapy.With a median follow-up of 15 months, the 2-year progression-freesurvival was estimated to be 75%, with a 2-year overall survivalof 95%. The ⁹⁰Y ibritumomab tiuxetan toxicity included grade3 hematologic toxicity in 12 of 20 patients; the most commongrade 3 toxic effects were neutropenia (12 patients) and thrombocytopenia(7 patients). Transfusions of red blood cells and/or plateletswere given to one patient. Conclusion: This study has established the feasibility, tolerability,and efficacy of this regimen for elderly patients with DLBCL. Key words: Chemotherapy, DLBCL, elderly patients, yttrium 90 ibritumomab tiuxetan Received for publication April 30, 2007. Revision received July 25, 2007. Revision received September 13, 2007. Accepted for publication November 12, 2007.     

Topical anesthesia: possible risk factor for endophthalmitis after cataract extraction

PURPOSE: To assess the relationship between the risk for acute endophthalmitis after cataract extraction and whether certain factors, such as surgeon qualification, numerical order, duration of surgery, operating theater, and type of anesthesia (topical or retrobulbar), could be modified to decrease the risk. SETTING: Single-center academic practice. METHODS: Two epidemiological studies were performed: a case-control study and a retrospective cohort study. The surgical records of all patients with clinically diagnosed endophthalmitis within 30 days after cataract surgery performed between February 2002 and September 2003 were reviewed. The endophthalmitis cases were compared with 108 randomly selected controls (4 controls per case). The global incidence of endophthalmitis and the incidence according to type of anesthesia were calculated. RESULTS: Of 5011 cataract extractions performed, 27 cases of endophthalmitis occurred. The incidence was 5.39 per 1000 procedures. An independent statistically significant relationship was found between endophthalmitis and the use of topical anesthesia (odds ratio [OR], 11.8; 95% confidence interval [CI], 2.4-58.7) and surgery longer than 45 minutes (OR, 7.2; 95% CI, 1.7-29.7) but not between the other variables. The incidence of endophthalmitis was 1.8 per 1000 cataract extractions with retrobulbar anesthesia and 6.76 per 1000 with topical anesthesia (relative risk [RR], 3.76; 95% CI, 0.89-15.85). After the start of the study period was extended to May 2001, the incidence of endophthalmitis was 1.3 per 1000 cataract extractions with retrobulbar anesthesia and 8.7 per 1000 with topical anesthesia (RR, 6.72; 95% CI, 1.63-27.63). CONCLUSION: Results suggest that there may be an association between topical anesthesia and endophthalmitis after cataract extraction.     

Peripheral T-cell lymphoma with a T follicular-helper phenotype: A different entity? Results of the Spanish Real-T study

Nodal peripheral T-cell lymphoma (PTCL) with a T follicular helper phenotype (PTCL-TFH) is a new type of PTCL. We aimed to define its clinical characteristics and prognosis compared to PTCL not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL). This retrospective observational study included 175 patients diagnosed with PTCL between 2008 and 2013 in 13 Spanish sites. Patient diagnosis was centrally reviewed, and patients were reclassified according to the World Health Organization (WHO) 2016 criteria: 21 patients as PTCL-NOS, 55 as AITL and 23 as PTCL-TFH. Median follow-up was 56.07 months (95% CI 38.7–73.4). Progression-free survival (PFS) and overall survival (OS) were significantly higher in patients with PTCL-TFH than in those with PTCL-NOS and AITL (PFS, 24.6 months vs. 4.6 and 7.8 months, respectively, p = 0.002; OS, 52.6 months vs. 10.0 and 19.3 months, respectively, p < 0.001). Histological diagnosis maintained an independent influence on both PFS (hazard ratio [HR] 4.1 vs. PTCL-NOS, p = 0.008; HR 2.6 vs. AITL, p = 0.047) and OS (HR 5.7 vs. PTCL-NOS, p = 0.004; HR 2.6 vs. AITL, p = 0.096), regardless of the International Prognostic Index. These results suggest that PTCL-TFH could have more favourable features and prognosis than the other PTCL subtypes, although larger series are needed to corroborate these findings.     

Clinical and pathological characteristics of peripheral T‐cell lymphomas in a Spanish population: a retrospective study

We investigated the clinicopathological features and prognostic factors of patients with peripheral T‐cell lymphoma (PTCL) in 13 sites across Spain. Relevant clinical antecedents, CD30 expression and staining pattern, prognostic indices using the International Prognostic Index and the Intergruppo Italiano Linfomi system, treatments, and clinical outcomes were examined. A sizeable proportion of 175 patients had a history of immune‐related disorders (autoimmune 16%, viral infections 17%, chemo/radiotherapy‐treated carcinomas 19%). The median progression‐free survival (PFS) and overall survival (OS) were 7·9 and 15·8 months, respectively. Prognostic indices influenced PFS and OS, with a higher number of adverse factors resulting in shorter survival (P < 0·001). Complete response (CR) to treatment was associated with better PFS (62·6 vs. 4 months; P < 0·001) and longer OS (67·0 vs. 7·3 months; P < 0·001) compared to no CR. CD30 was expressed across all subtypes; >15% of cells were positive in anaplastic lymphoma kinase‐positive and ‐negative anaplastic large‐cell lymphoma and extranodal natural killer PTCL groups. We observed PTCL distribution across subtypes based on haematopathological re‐evaluation. Poor prognosis, effect of specific prognostic indices, relevance of histopathological sub‐classification, and response level to first‐line treatment on outcomes were confirmed. Immune disorders amongst patients require further examination involving genetic studies and identification of associated immunosuppressive factors.     

MYC protein expression and genetic alterations have prognostic impact in patients with diffuse large B-cell lymphoma treated with immunochemotherapy

MYC alterations influence the survival of patients with diffuse large B-cell lymphoma. Most studies have focused on MYC translocations but there is little information regarding the impact of numerical alterations and protein expression. We analyzed the genetic alterations and protein expression of MYC, BCL2, BCL6, and MALT1 in 219 cases of diffuse large B-cell lymphoma. MYC rearrangement occurred as the sole abnormality (MYC single-hit) in 3% of cases, MYC and concurrent BCL2 and/or BCL6 rearrangements (MYC double/triple-hit) in 4%, MYC amplifications in 2% and MYC gains in 19%. MYC single-hit, MYC double/triple-hit and MYC amplifications, but not MYC gains or other gene rearrangements, were associated with unfavorable progression-free survival and overall survival. MYC protein expression, evaluated using computerized image analysis, captured the unfavorable prognosis of MYC translocations/amplifications and identified an additional subset of patients without gene alterations but with similar poor prognosis. Patients with tumors expressing both MYC/BCL2 had the worst prognosis, whereas those with double-negative tumors had the best outcome. High MYC expression was associated with shorter overall survival irrespectively of the International Prognostic Index and BCL2 expression. In conclusion, MYC protein expression identifies a subset of diffuse large B-cell lymphoma with very poor prognosis independently of gene alterations and other prognostic parameters.