Correction to: Predictive and prognostic clinical and pathological factors of nivolumab efficacy in non-small-cell lung cancer patients.

Clinical and Translational Oncology.

Molecular subtypes in early colorectal cancer associated with clinical features and patient prognosis.

PURPOSE: After surgical resection, an ample prognosis variability among stages is observed. Multiple prognostic factors are individually studied and some CRC classifiers have been proposed. Not one have been implemented into clinical practice. METHODS/PATIENTS: We classified 105 patients with resected CRC (stage I-III) into five molecular subtypes using BRAFV600E and RAS (KRAS; NRAS) status, and the expression of DNA mismatch repair (MMR) proteins (MLH1 and MSH2). Clinicopathological features and DFS) of distincts groups were evaluated. RESULTS AND CONCLUSIONS: RAS and BRAFV600E mutations were detected in 43.8 and 11.4% of patients, respectively. 19% of tumours had lack of expression of any MMR proteins reflecting a system deficiency (dMMR). Patients with any RAS mutation had lower DFS that patients with RAS wild type (wt) (40.23 vs 45.26 months; p value = 0.035). Of a total of five molecular subtypes, three were MMR proficient (pMMR): RAS mutated (39%), BRAFV600E mutated (6.7%) and RAS/BRAFV600E wt (35.2%); and two were dMMR: BRAFV600E mutated (4.8%) and BRAFV600E wt (14.3%). Left side tumours were more frequently observed in pMMR/RAS and BRAFV600E wt subtype, and right side tumours in dMMR subtypes. Among the three pMMR subtypes, a benefit survival was observed for patients without any mutation in BRAFv600E or RAS oncogenes (median of DFS = 45.5 vs 40.98 months in RAS mutated group; p = 0.084 and vs 34.13 in BRAFv600E mutated group; p = 0.031). Molecular classification using these biomarkers can be useful to identify groups with differences in prognosis.

Predictive and prognostic clinical and pathological factors of nivolumab efficacy in non-small-cell lung cancer patients.

BACKGROUND: Immunotherapy increases overall response rate (ORR) and overall survival (OS) in patients with non-small-cell lung cancer (NSCLC). Prognostic and predictive factors are a high need. PATIENTS AND METHODS: Retrospective review of NSCLC patients treated with nivolumab was performed. Analyzed variables included age, sex, stage, performance status (PS), location of metastases, presence of tumour-related symptoms and comorbidities, number of metastasis locations, previous chemotherapy, anti-angiogenic and radiotherapy treatments, and analytical data from the standard blood count and biochemistry. RESULTS: A total of 175 patients were included. Median age was 61.5 years, 73.1% were men, 77.7% were ECOG-PS 0-1, and 86.7% were included with stage IV disease. Histology was non-squamous in 77.1%. Sixty-five received nivolumab in second line (37.1%). Thirty-eight patients had brain metastasis (22%), and 39 (22.3%) liver metastasis and 126 (72%) had more than one metastatic location. The ORR was 15.7% with median Progression free survival (PFS) 2.8 months and median OS 5.81 months. Stage III vs IV and time since the beginning of the previous line of treatment ≥ 6 vs < 6 months were associated with better response. PS 2, time since the previous line of treatment < 6 vs ≥ 6 months, and more than one metastatic location were independently associated with shorter OS in multivariable analysis (7.8 vs 2.7 months, 11.2 vs 4.6 months, and 9.4 vs 5.1 month). Finally, time since the previous treatment < 6 vs ≥ 6 months and more than one metastatic location were independently associated with shorter PFS in multivariable analysis (4.3 vs 2.3 months and 4.7 vs 2.3 months). CONCLUSION: Poor PS, short period of time since the previous treatment, and more than one metastatic location were associated with poorer prognostic.

High pKDR immunohistochemical expression is an unfavourable prognostic biomarker in patients with advanced colorectal cancer treated with chemotherapy plus bevacizumab.

PURPOSE: To analyse the prognostic role of the immunohistochemical expression of pKDR in patients with advanced colorectal cancer treated with oxaliplatin and fluoropyrimidines combination chemotherapy with or without bevacizumab. METHODS: Retrospective multicentre study, carried out at four hospitals in the Valencian Community (Spain). Patients evolution was compared based on the immunohistochemical expression of pKDR, classified using 4 categories: 0 (undetectable), 1 (mild), 2 (moderate) and 3 (high intensity). Patients were divided into two groups for the analysis: group 1 with low expression (0-1) vs. group 2 with high expression (2-3). RESULTS: Histological samples for the pKDR analysis were available for 84 of the 112 patients selected. Seven (8.3 %) had undetectable or mild expression of pKDR (Group 1) and 77 (91.7 %) showed moderate or high expression of pKDR (Group 2). Response rate in Group 1 was 100 % compared to 54.2 % in Group 2 (p = 0.019). Progression-free survival (PFS) (15 vs. 12 months, p = 0.4) and overall survival (OS) (28 vs. 22 months, p = 0.09) were numerically but not significantly higher in patients from Group 1 vs. Group 2. Patients from Group 2 who received bevacizumab presented a significantly higher PFS (13 vs. 11, p = 0.015) and a numerically higher OS (23 vs. 17 months, p = 0.27) than those treated exclusively with chemotherapy. CONCLUSIONS: Our results suggest that the absence or low expression of pKDR is associated with a better prognostic profile in patients with advanced colorectal cancer treated with chemotherapy and bevacizumab. Patients with a high pKDR expression benefit from the combination of chemotherapy with bevacizumab.

[Antileukotrienes. Their use in pediatrics]. / Antileucotrienos. Su uso en pediatría.

The leukotriene antagonists have represented the first novelty in the treatment of asthma over the last 20 years. Their easy oral administration that favours a suitable completion of the treatment, especially on children, together with the proven efficiency and their apparent safety, gave rise to the fact in 1999 the asthma committee of the Spanish Society of Clinical Immunology and Paediatric Allergology (SSCIPA) in the bronchial asthma treatment guide that was presented a year ago during the XXIII National Congress of our Society, considered the antileukotrienes, together with the chromones, as important medicines for stage 2 asthma (frequent episodes) and as useful medicines to reduce the need to take corticoides in cases of persistent asthma. A year later, in our study we proposed to value too suitability or non suitability of this positioning, in the light of the new investigations published and from our own experience. We believe that the bibliography available to date shows that the agonist cysteinyl-leukotrienes are anti-inflammatory medicines, that have an efficiency similar to that of low doses of inhaled corticoids, equally efficient in controlling bronchospasm-induced exercise and they have a good safety profile. We present two studies that are the result of our own experience, one carried out on children with persistent asthma and the other on children with frequent episodic asthma, from which we can apparently deduce that both nedocromil (2 inhalations every 8 hours) and montelukast (5 mg every 24 hours) are medicines that have similar efficacy in the control of asthma. We conclude that the antileukotrienes, together with the chromones, should be seen as important medicines when treating infant asthma.