Simona Carnio

Extending Survival of Stage IV Non-Small Cell Lung Cancer☆

Most of patients with newly diagnosed non-small cell lung cancer (NSCLC) present with locally advanced or metastatic disease. In this setting the goal of treatment is to prolong survival and to control disease- and treatment-related symptoms. Currently systemic cytotoxic chemotherapy remains the first-line treatment for most patients with stage IV NSCLC, but preferred treatments are now defined by histology and based on the presence of specific molecular abnormalities. In first-line the combination of platinum plus pemetrexed with or without bevacizumab is a reasonable choice in patients with non-squamous NSCLC. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) as first-line therapy are the recommended for patients with EGFR-sensitizing mutations. A small-molecule TKI of anaplastic lymphoma kinase (ALK), crizotinib, showed pronounced clinical activity in the treatment of patients with NSCLC positive for EML4-ALK and it has rapidly entered into daily clinical practice. Currently no agents are specifically approved for the treatment of squamous cell carcinoma of the lung. Second-line treatments include docetaxel, pemetrexed, or erlotinib as single agents. There is a growing evidence that cytotoxics are better than EGFR-TKIs in EGFR wild-type patients. In the setting of the third line, the only approved agent is erlotinib. In elderly patients with good performance status (PS), doublet chemotherapy including platinum should not be excluded, especially for those patients 70-75 years of age without comorbidities. The better selection of patients, the identification of specific predictive biomarkers, a reasonable sequencing of all active and available treatments, including targeted therapies and cytotoxic, may significantly contribute to extend the natural history of stage IV NSCLC.

Prognostic and predictive biomarkers in early stage non-small cell lung cancer: tumor based approaches including gene signatures.

In early stage non-small cell lung cancer (NSCLC) large randomized trials have demonstrated that in patients with radically resected disease adjuvant chemotherapy improves 5-year survival rates. However, a customization of systemic treatment is needed to avoid treatments in patients cured by surgery alone or to justify the use of adjuvant chemotherapy in high risk patients, including those in stage IA. Recently, the possibility of identifying prognostic and predictive factors related to the genetic signatures of the tumor that could affect adjuvant and neo-adjuvant treatment choices for resectable non-small cell lung cancer (NSCLC) has been of interest. This review summarizes the current status and future opportunities for clinical application of genotyping and genomic tests in early NSCLC.

Moving from histological subtyping to molecular characterization: new treatment opportunities in advanced non-small-cell lung cancer

Over the last 10 years, the systemic treatment of advanced non-small-cell lung cancer has progressively moved away from the ‘one-size-fits-all’ approach to histological subtyping. Currently, there is a progressive implementation of targeted therapies based on specific molecular characteristics such as the EGF receptor sensitizing mutations and the anaplastic lymphoma kinase rearrangements. Despite the availability of effective agents against these abnormalities, acquired resistance is still a major issue. A new generation of tyrosine kinase inhibitors for EGF receptor and anaplastic lymphoma kinase targeting acquired resistance mechanisms have been recently investigated. Several promising tyrosine kinase inhibitors that hit other targets are also in clinical development, including: rat sarcoma gene/MEK, BRAF1, PIK3A, c-mesenchymal-epithelial transition, c-ros oncogene 1, rearranged during transfection, human EGFR 2, FGFR, VEGFR, PDGFR and discoidin death receptor 2. Furthermore, new advances in immunology have been achieved through the discovery of vaccines and immune checkpoint pathways such as the cytotoxic T-lymphocyte-associated antigen-4, programmed cell death protein 1 and its ligands.

Patients' Attitudes and Physicians' Perceptions Toward Maintenance Therapy for Advanced Non–Small-cell Lung Cancer: A Multicenter Italian Survey

Introduction Pemetrexed maintenance therapy (MT) after induction with platinum‐based chemotherapy has recently become a common treatment strategy for advanced nonsquamous non–small‐cell lung cancer (NSCLC). However, the benefits of MT should be weighed with consideration of the patients’ perceptions and preferences. The aim of the present study was to evaluate patients’ attitudes toward MT and to describe physicians’ awareness of their patients’ inclinations. Materials and Methods We administered a 12‐question anonymous survey and the Distress Thermometer Questionnaire to patients with advanced or recurrent nonsquamous NSCLC. The survey was also distributed to the referring physicians. Results From December 2014 to July 2015, 92 patients and 37 physicians were enrolled. All 92 patients completed the questionnaire at T0 (before starting chemotherapy) and 56.5% also did so at T1 (after completion of induction). The physicians completed the survey only at T0. Most patients had a positive attitude toward MT at both T0 (78.9%) and T1 (86.5%), and 100% of the physicians thought their patients would be in favor of MT. The physicians believed that their patients’ attitudes toward MT would decrease proportionally with the reduction in the magnitude of the overall survival increase and expected benefits. The decrease expected by the physicians was much greater than that reported by the patients. This was especially true for an overall survival increase as small as 1 month (51.9% of patients accepting MT vs. 13.5% supposed by physicians) or when the only treatment benefit was radiologic tumor stabilization (69.3% of patients accepting MT vs. 37.8% supposed by physicians). Conclusion NSCLC patients have a generally positive attitude toward MT, which is not directly proportional to the expected benefits and greater than the attitude expected by physicians. Micro‐Abstract One question is how long patients with advanced non–small‐cell lung cancer wish to receive therapy. The perceptions of > 100 patients and physicians were analyzed to compare different prognostic conditions. The patients’ attitudes were generally positive and not directly linked to the expected benefits, suggesting that other factors in conjunction with the clinical assessment, such as the doctor–patient relationship, should be considered to understand patients’ motivations.

Fatigue in lung cancer patients: symptom burden and management of challenges

Lung cancer (LC) remains the most common cause of cancer death in several countries across the world. Fatigue is the most frequently reported symptom in LC patients throughout the entire course of disease, and all international guidelines recommend early screening for cancer-related fatigue (CRF) and symptoms that can affect patients’ quality of life. In patients with LC, fatigue belongs to the symptom cluster of pain, depression, and insomnia, which are commonly observed simultaneously, but are typically treated as separate although they may have common biological mechanisms. The treatment of CRF remains one of the difficult areas in the oncology field: scarce evidence supports pharmacological therapies, while some interesting data arising indicates alternative remedies and physical exercise seem to be one of the most effective approaches for CRF at any stage of LC.

Chemotherapy-induced nausea and vomiting (CINV) in patients with advanced lung cancer during the first-line treatment: assessment by physicians, nurses, and patients from an Italian multicenter survey

PurposeChemotherapy-induced nausea and vomiting (CINV) still represents a common side-effect of chemotherapy, and often, its perception differs between patients and healthcare professionals. The aim of this study was to evaluate the agreement on the perception of CINV and other items among clinicians, patients, and nurses.MethodsThis observational prospective study was part of an evaluation program promoted by the Women Against Lung Cancer in Europe (WALCE) Onlus. From August 2015 to February 2016, a survey was administered in 11 oncologic institutions to 188 stage IV lung cancer patients and to their oncologists and nurses during first-line chemotherapy. Our survey investigated 11 aspects: anxiety, mood, weakness, appetite, nausea, vomiting, pain, drowsiness, breath, general condition, and trust in treatments. These items were assessed through Numerical Rating Scale at four consecutive evaluations: at T0 (immediately prior to the first cycle), at T1 (immediately prior to the second cycle), at T2 (immediately prior to the third cycle), and at T3 (immediately prior to the fourth cycle). Clinician versus patient (CvP), nurse versus patient (NvP), and clinician versus nurse (CvN) agreements were estimated applying Weighted Cohen’s kappa. A multivariate logistic model and generalized equation estimates were applied to evaluate factors possibly influencing CINV development.ResultsThe incidence of patients reporting CINV varied from 40% at T0 to 71% at T3. Both CvP and NvP agreement on the investigated items were mainly moderate, slightly increasing over time, and becoming substantial for some items, in particular for NvP. Pre-chemotherapy anxiety in its mild, moderate, and severe manifestations, as well as mild, moderate, and severe anxiety experienced after chemotherapy start, exposed patients to a higher risk of anticipatory and acute/delayed CINV, respectively.ConclusionsDespite clinical staff awareness of patients’ status and perceptions, CINV still represents a clinical problem. This study confirms that particular attention should be paid to anxiety due to its key role in CINV development.

A challenge to overcome: the maintenance of the global quality of life in patients with advanced or metastatic non-small cell lung cancer

ABSTRACT Introduction: The global quality of life (QoL) in patients with advanced or metastatic non-small cell lung cancer (NSCLC) is a major clinical problem. Often the QoL’s data from clinical trials do not reflect the real life. Further improvements are needed to get reproducible methods to assess patients’ QoL within oncology units in daily clinical practice. Areas covered: This review explored QoL’s aspects of NSCLC patients through a collection of articles published in the last five years on PubMed. The aim was to highlight the importance of QoL and its management in these patients. Expert commentary: A better interpretation of clinical trials’ results is necessary, to identify more adequately the risks/benefits profile of the chosen treatment. The introduction of the early palliative care (EPC) and the conduction of studies focused on survival objectives as well as on QoL might be a valuable help to improve NSCLC management.

How to Personalize Perioperative Chemotherapy in Early Non-small Cell Lung Cancer?

Disseminated micrometastatic disease often limits the effectiveness of aggressive locoregional treatment strategies in operable non-small cell lung cancer (NSCLC). The perioperative chemotherapy (neo- and adjuvant chemotherapy) results in a minimal survival advantage and is associated with a significant toxicity in a subgroup of patients. A proportion of early-stage patients are cured by local treatment modality alone and associated systemic treatment ends in a possible overtreatment, while in other patients, with the same pathological stage, systemic treatment is not effective at all. Therefore, there is a critical need to individualize systemic treatment in early-stage NSCLC. When treatment personalization is considered, two are the main goals: from one side, to reduce toxicity and, on the other, to improve efficacy outcomes. Currently new prospective trials for early stage are ongoing. In these studies patients are randomized to experimental treatment with cytotoxic or targeted agents that are customized by molecular pathways, genomic characterization, and/or immunological targets. Hopefully, awaited results from these trials will provide us new information for the management of stages I–III NSCLC.

Multidisciplinary management of non small cell lung cancer (NSCLC) in stage III: clinical case description. Recommendations and state of the art

Lung cancer is the leading cause of cancer death in industrialized countries with progressive increase of its mortality rate. Non Small Cell Lung Cancer (NSCLC ) is approximately 80-85% of all lung cancers, being adenocarcinoma and squamous cell carcinoma the most common histologies. The majority of the patients with stage III clinical stage, presents a mediastinal lymph node involvement described with computed tomography (TC) and/or positron emission tomography (PET). The current approach to patients with NSCLC is multidisciplinary, especially for those staged as potentially operable, both for staging and for a correct definition of best treatment strategy. Updated international and national Guidelines and recommendations can provide valuable support to the clinician. The case described concerns the accidental detection of a tumour in the lung in a 58-year-old man with arterial hypertension controlled with ACE inhibitors. The treatments agreed after a multidisciplinary approach are cisplatin and docetaxel, the surgical resection, and the radiotherapy. After three months the patient has neither metastasis nor relapse.