Treatment options beyond immunotherapy in patients with wild-type lung adenocarcinoma: a Delphi consensus.

PURPOSE: Immunotherapy-based approaches are standard first-line treatments for advanced/metastatic lung cancer or for chemoradiotherapy consolidation in locally advanced disease. Uncertainty on how to treat patients at disease progression prompted us to develop a consensus document on post-immunotherapy options in Spain for patients with advanced wild-type lung adenocarcinoma. METHODS: After extensive literature review, a 5-member scientific committee generated 33 statements in 4 domains: general aspects (n = 4); post-durvalumab in locally advanced disease (n = 6); post-first-line immunotherapy ± chemotherapy in advanced/metastatic disease (n = 11); and post-first-line platinum-based chemotherapy in advanced/metastatic disease (n = 12). A panel of 26 lung cancer experts completed 2 Delphi iterations through an online platform rating their degree of agreement/disagreement (first-round scale 1-5 and second-round scale 1-4, 1 = strongly disagree, 4/5 = strongly agree) for each statement. Second-round consensus: ≥ 70% of responses were in categories 1/2 (disagreement) or 3/4 (agreement). RESULTS: Consensus was reached for 2/33 statements in the first Delphi round and in 29/31 statements in the second round. Important variables informing treatment at disease progression with an immunotherapy-based treatment include: disease aggressiveness, previous treatment, accumulated toxicity, progression-free interval, PD-L1 expression, and tumour mutational burden. A platinum-based chemotherapy should follow a first-line immunotherapy treatment without chemotherapy. Treatment with docetaxel + nintedanib may be appropriate post-durvalumab in refractory patients or following progression to first-line chemotherapy + immunotherapy, or second-line chemotherapy after first-line immunotherapy, or first-line chemotherapy in some patients with low/negative PD-L1 expression, or second-line immunotherapy after first-line chemotherapy. CONCLUSIONS: To support decision making following progression to immunotherapy-based treatment in patients with advanced wild-type lung adenocarcinoma, a consensus document has been developed.

SEOM clinical guidelines for the treatment of non-small cell lung cancer (2018).

Non-small cell lung cancer (NSCLC) accounts for up to 85% of all lung cancers. The last few years have seen the development of a new staging system, diagnostic procedures such as liquid biopsy, treatments like immunotherapy, as well as deeper molecular knowledge; so, more options can be offered to patients with driver mutations. Groups with specific treatments account for around 25% and demonstrate significant increases in overall survival, and in some subgroups, it is important to evaluate each treatment alternative in accordance with scientific evidence, and even more so with immunotherapy. New treatments similarly mean that we must reconsider what should be done in oligometastatic disease where local treatment attains greater value.

A consensus statement on the gender perspective in lung cancer.

Lung cancer is the most common cancer globally and has the highest mortality. Although this disease is not associated with a particular gender, its incidence is rising among women, who are diagnosed at an increasingly younger age compared with men. One of the main reasons for this rise is women taking up smoking. However, many non-smoking women also develop this disease. Other risk factors implicated in the differential development of lung cancer in women are genetic predisposition, tumour histology and molecular profile. Proportionally more women than men with lung cancer have a mutation in the EGFR gene. This consensus statement reviews the available evidence about the epidemiological, biological, diagnostic, therapeutic, social and psychological aspects of lung cancer in women.

Long-term survival in advanced non-squamous NSCLC patients treated with first-line bevacizumab-based therapy.

BACKGROUND/AIM: First-line bevacizumab-based therapies have been shown to improve clinical outcomes in patients with non-squamous non-small-cell lung cancer (NSCLC). We aimed to descriptively analyse patients with non-squamous NSCLC who received a long-term period of maintenance bevacizumab. PATIENTS AND METHODS: This retrospective study included 104 patients who had already reached a progression-free survival (PFS) of at least 9 months. RESULTS: Median overall survival and PFS were 30.7 and 15.1 months, respectively. The overall response rate was 83 %. Weight loss ≤5 %, ECOG PS = 0, or low number of metastatic sites seem to be predictive factors of good evolution. The incidence of bevacizumab-related adverse events appeared to be similar as the previous studies. CONCLUSION: Our findings show that there is a long-term survivor group whom the administration of bevacizumab resulted in a relevant prolongation of response without new safety signals. Due to the population heterogeneity, it was not possible to identify the standardised predictive factors.

Thyroid cancer: SEOM clinical guidelines.

Thyroid cancer (TC) is the most common type of endocrine malignancy and accounts for nearly 3% of all malignancies. The incidence of TC in Spain was 5/100,000 in women and 1.9/100,000 in men in 2013. The diagnosis of TC usually follows the identification of a thyroid nodule on physical examination or as an incidental finding on diagnostic imaging performed for other reasons. In most of the cases, the prognosis is excellent but despite low mortality rates, local recurrence occurs in up to 20%, and distant metastases can occur in approximately 10% at 10 years. The better knowledge of molecular biology of TC has allowed to the development of new targeted agents directed to the main pathways involved in TC pathogenesis. Knowing all these new strategies will help us face the therapeutic management of TC more effectively.

Concurrent radiotherapy plus epidermal growth factor receptor inhibitors in patients with human papillomavirus-related head and neck cancer.

PURPOSE: Concurrent radio-chemotherapy (RT-CT) is the standard treatment for locally advanced head and neck squamous cell carcinoma (LA-HNSCC), but RT plus epidermal growth factor receptor (EGFR) inhibitors is an effective option when CT is not appropriate. Human papillomavirus (HPV) is associated with an improved prognosis in LA-HNSCC; however, it has not been fully studied as a prognostic factor after RT + EGFR inhibitors. EXPERIMENTAL DESIGN: Immunohistochemical expression of p16INK4A and PCR of HPV16 DNA were retrospectively analyzed in tumor blocks from 52 stage III/IV LA-HNSCC patients treated with RT + EGFR inhibitors. Disease-free survival (DFS) and overall survival (OS) were analyzed by the Kaplan-Meier method. RESULTS: DNA of HPV16 was found in six of 52 tumors (12 %) and p16 positivity in eight tumors (15 %). After a median follow-up time of 45 months (6-110), p16-positive patients treated with RT + EGFR inhibitors showed an improved DFS (2-year DFS 75 vs. 44 %, HR 0.25, 95 % CI 0.06-0.99, p = 0.047) compared with p16-negative patients. These differences were outperformed when compared by HPV16 status (2-year OS rates of 83 vs. 58 %, HR 0.17, 95 % CI 0.02-0.99, p = 0.049 and 2-year DFS rates of 83 vs. 45 %, HR 0.17, 95 % CI 0.02-0.99, p = 0.049). In the Cox regression analysis with OS as the end point, ECOG 0-1 was the only prognostic factor independently associated with a good prognosis in the multivariable analysis. CONCLUSION: In this study, p16/HPV16-positive patients with LA-HNSCC treated with RT + EGFR inhibitors showed a better survival, not confirmed in multivariate analysis.

SEOM clinical guidelines for the treatment of non-small cell lung cancer (NSCLC) 2013.

Lung cancer remains the most commonly diagnosed cancer worldwide and the leading cause of cancer-related mortality. More than 80 % of all newly diagnosed cases of lung cancer are non-small cell lung cancer (NSCLC). Despite recent advances, 40 % of patients still have advanced disease at the moment of diagnosis. Clinical information, pathological diagnosis and molecular assessment are needed to guide the systemic therapy, whereas discussion within an experienced team is key to adequately select the most appropriate multidisciplinary strategies. The purpose of this article is to provide updated recommendations for the management of these patients.

Immunohistochemical expression of cyclooxygenase-2 in patients with advanced cancer of the larynx who have undergone induction chemotherapy with the intention of preserving phonation.

INTRODUCTION: Cyclooxygenase-2 (COX2) is an enzyme that plays a role in different stages of the carcinogenic process and has prognostic and predictive values that have not yet been established. The objective of this study was to evaluate the role of COX2 overexpression in advanced squamous cell carcinoma of the larynx that has been treated with a phonation conservation protocol. MATERIALS AND METHODS: This study included a retrospective analysis of 59 patients with resectable tumours that were treated with chemotherapy (CT) and/or radiation therapy (RT). The expression levels of COX2, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and vascular endothelial growth factor receptor (VEGFR-2) in collected biopsy specimens were determined via immunohistochemistry. RESULTS: Forty-four percent of the included samples demonstrated overexpression of COX2. In the statistical analysis, COX2 overexpression did not correlate with other clinical or treatment efficacy prognostic factors; however, the median global survival (OS) of patients whose tumours expressed COX2 was 79 months, whereas COX2-negative patients had a median OS of only 38 months, although this finding did not reach statistical significance. The other analysed biological parameters did not demonstrate a significant relationship with COX2. CONCLUSIONS: COX2 overexpression was a common finding in our study. The results obtained did not reveal relationships with established prognostic categories; however, the difference in survival between patients with and without COX2 expression justifies the need for future prospective studies that utilise a larger patient sample size.

SEOM guidelines for the management of non-small-cell lung cancer (NSCLC).

Lung cancer is currently the most common malignancy and also the leading cause of mortality related to cancer in the world [1]. The crude incidence of lung cancer in the EU is 52.5/100,000/year, while the mortality 48.7/100,000/year. Among men the rates are 82.5 and 77.0/100,000/year, and among women 23.9 and 22.3/100,000/year, respectively. Non-small-cell lung cancer (NSCLC) accounts for 80% of all cases. In Spain, there were 16,879 deaths in men, with a mean age of 68 years, and 2634 deaths in women, with a mean age of 66 years. The incidence of lung cancer in Spain was 68.3/100,000 among men and 13.8/100,000 among women, according to the latest data published in the year 2006 by the Instituto Nacional de Estadística. About 90% of lung cancer mortality among men (and 80% among women) is attributable to smoking.