Efimia Boutsikou

Treatment of non-small cell lung cancer (NSCLC)

Radical surgery is the standard of care for fit stage I non-small cell lung cancer (NSCLC) patients. Adjuvant treatment should be offered only as part of an investigation trial. Stage II and IIIA adjuvant cisplatin-based chemotherapy remains the gold standard for completely resected NSCLC tumors. Additionally radiotherapy should be offered in patients with N2 lymph nodes. In advanced stage IIIB/IV or inoperable NSCLC pts, a multidisciplinary treatment should be offered consisted of 4 cycles of cisplatin-based chemotherapy plus a 3(rd) generation cytotoxic agent or a cytostatic (anti-EGFR, anti-VEGFR) drug.

Malignant pleural mesothelioma: current and future perspectives

Mesothelioma still remains an occupational related cancer with severe outcome. It is usually diagnosed at advanced stage since it does not demonstrate early symptoms. Several efforts have been made towards removing all materials inducing mesothelioma in the work setting and new work protection measures have been applied. Although we have new targeted treatments and radical surgery as arrows in the quiver, the type of mesothelioma and early diagnosis still remain the best treatment approach. Novel treatment modalities have been explored and several others are already on the way. In the current review we will present current data for mesothelioma and future perspectives.

Immunomodifiers in combination with conventional chemotherapy in small cell lung cancer: a Phase II, randomized study

Purpose To evaluate the effect of immunotherapy on response, survival, and certain immune markers in patients with small cell lung cancer (SCLC) who are receiving chemotherapy. Patients and methods Patients with SCLC (n = 164) were assigned to receive either chemotherapy alone (group A) or a combination of chemotherapy and immunotherapy as follows: interferon α (IFN-α; 3 million IU) 3 times per week (group B); IFN-γ (3 million IU) 3 times per week (group C); and IFN-α and IFN-γ (1.5 million IU of each) 3 times per week (group D). Chemotherapy was the same for all groups and consisted of eight cycles with carboplatin 5.5 mg/m2 intravenously on day 1, ifosfamide 3.5 mg/m2 intravenously on day 1, and etoposide 200 mg/m2 total dose taken orally on days 1 through 3, every 28 days. Patients completing chemotherapy were restaged, and those who were found to have limited disease received primary site and prophylactic cranial irradiation. Immunotherapy was continued throughout these treatments and during the follow-up period. Blood was taken before each course of chemotherapy and during follow-up to measure CD3+ lymphocytes, CD3+CD4+ lymphocytes, CD3+CD8+ lymphocytes, natural killer cells, and natural killer T cells. Results Differences in response and survival were not significantly different when all patients were considered. However, among patients with limited disease, Kaplan–Meier analysis disclosed a survival benefit for group B (P , 0.05). The analysis of immunologic measurements revealed that the improvement of immune markers was always accompanied by clinical improvement, whereas deterioration of all markers was accompanied by disease progression (result not statistically significant except for group C; P , 0.05). Conclusion Among cytokines used in the study, only IFN-α seems to confer a survival benefit to patients with SCLC with limited disease. However, immunotherapy remains a challenge in the treatment of lung neoplasms and should be further explored.

New dilemmas in small-cell lung cancer TNM clinical staging

Background Many patients with limited disease (LD) behave similarly to those with extensive disease (ED) from a prognostic point of view. On the other hand, a proportion of patients with ED small-cell lung cancer (SCLC) behave similarly to those with LD. Patients and methods In this retrospective study analysis, 764 patients with proven SCLC were included and managed with the same therapeutic protocols. Of these patients, 278 (36.4%) had LD, while 486 (63.6%) had ED. Results No statistically significant difference was observed for survival for IA and IB disease stages (P = 0.254) and between IIA and IIB stages (P = 0.256) according to the new tumor, node, metastasis (TNM) staging classification classification. In addition, no statistical significant difference was observed for survival between patients with (IIA + IIB) and IIIA (P = 0.951), (IIA + IIIA, P = 0.658), and (IIB + IIIA, P = 0.573) stages. Statistical significant difference was observed for survival among the LD SCLC patients with (IA + IB), (IIA + IIB + IIIA), and IIIB stages (P < 0.001). Similarly, statistical significance was observed for ED SCLC patients with (IIA + IIB + IIIA), IIIB, and IV stages (P < 0.001). Conclusions Although stratification of SCLC patients in LD and ED is generally satisfactory, the TNM staging system is recommended for more detailed prognostic information and treatment evaluation in these patients.

Tumour necrosis factor, interferon-gamma and interleukins as predictive markers of antiprogrammed cell-death protein-1 treatment in advanced non-small cell lung cancer: a pragmatic approach in clinical practice:

Background: The emergence of novel antiprogrammed cell death protein-1 (PD-1) inhibitors in non-small cell lung cancers (NSCLC) has revolutionized the therapeutic landscape of this disease. Although overall survival (OS) has improved in the first- and second-line therapy settings for advanced NSCLC, the benefit is not universal. In a climate of global scrutiny for healthcare costs and potential for toxicities related to immunotherapy, appropriate patient selection is crucial. The aim of this study was to evaluate potential prognostic and predictive biomarkers interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α) and a panel of interleukins (ILs) in the peripheral blood, and assess any correlation with response to anti-PD-1 inhibition, progression-free survival and OS in NSCLC patients. Methods: We prospectively studied 26 NSCLC patients that received immunotherapy (either pembrolizumab or nivolumab). IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10 and IL-12 were analyzed by flow cytometry at the time of diagnosis and at 3 months after initiation of anti-PD-1 inhibition. Results: Increased cytokine values (IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-6 and IL-8) at the time of diagnosis and at 3 months after initiation of treatment were significantly correlated with improved response to immunotherapy and prolonged OS. There was no correlation between cytokine levels and programmed cell death ligand-1 (PD-L1) expression. Conclusions: Increased IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10 and IL-12 levels resulted in better response to NSCLC anti-PD-1 inhibition and longer survival, and this could potentially play an important role in selecting patients that would benefit from anti-PD-1 inhibitors.

042. Denosumab-associated osteonecrosis of the jaw in NSCLC patient: a case report

Background Osteonecrosis of the jaw (ONJ) following bisphosphonate use is well documented. However, to our knowledge, there are few cases reported on ONJ related to the use of other pharmaceutical agents, such as denosumab—a receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor that has recently been approved for the prevention of SRE in patients with osteoporosis and solid tumors with metastases to bone.