Comorbidity in Small Cell Lung Cancer: Prognostic Impacts of Hypertension/Coronary Artery Disease, Diabetes Mellitus, and Chronic Obstructive Pulmonary Disease.

Comorbidity, the most important components of which are hypertension/coronary artery disease (HTN/CAD), diabetes mellitus (DM), and chronic obstructive pulmonary disease (COPD), is frequently encountered in small cell lung cancer (SCLC) patients. We aimed to assess the possible impacts of these major comorbidities on the prognoses of SCLC patients. A total of 378 SCLC patients were analyzed retrospectively. We did not ascertain the effect of comorbidity on survival in SCLC patients in general; and similarly, the presence of HTN/CAD and COPD did not adversely affect the outcome. However, lower survival rates were observed in patients with SCLC coexisting with DM.

Efficacy and safety profile of COVID-19 vaccine in cancer patients: a prospective, multicenter cohort study.

Aim: To compare the seropositivity rate of cancer patients with noncancer controls after inactive SARS-CoV-2 vaccination and evaluate the factors affecting seropositivity. Method: Spike IgG antibodies against SARS-CoV-2 were measured in blood samples of 776 cancer patients and 715 noncancer volunteers. An IgG level ≥50 AU/ml is accepted as seropositive. Results: The seropositivity rate was 85.2% in the patient group and 97.5% in the control group. The seropositivity rate and antibody levels were significantly lower in the patient group (p < 0.001). Age and chemotherapy were associated with lower seropositivity in cancer patients (p < 0.001). Conclusion: This study highlighted the efficacy and safety of the inactivated vaccine in cancer patients. Clinical Trials Registration: NCT04771559 (ClinicalTrials.gov).

Cancer patients are at high risk for infection with SARS-CoV-2 and of developing the associated disease, COVID-19, which therefore puts them in the priority group for vaccination. This study evaluated the efficacy and safety of inactive SARSCoV-2 vaccination, an inactivated virus vaccine, in cancer patients. The immune response rate, defined as seropositivity, was 85.2% in the cancer patient group and 97.5% in the control group. The levels of antibodies, which are blood markers of immune response to the vaccine, were also significantly lower in the patient group, especially in those older than 60 years and receiving chemotherapy. These results highlight the importance of determining the effective vaccine type and dose in cancer patients to protect them from COVID-19 without disrupting their cancer treatment.

The relationship of PET/CT SUVmax with EGFR mutation status and ALK rearrangement in lung adenocarcinoma.

OBJECTIVE: Epidermal growth factor receptor mutations (EGFRm) and rearrangement of the anaplastic lymphoma kinase gene (ALKr) can be targeted for precision therapy in lung adenocarcinoma (LADC). As molecular profiling is not available for all, patient stratification can be achieved using non-invasive and economic tools, such as positron emission tomography/computed tomography (PET/CT). We aimed to evaluate the relationships between fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT maximum standardized uptake value (SUVmax) of primary tumors (pSUVmax) and lymph nodes (nSUVmax) and the EGFRm and ALKr status in a large series of Turkish LADC patients. MATERIAL AND METHODS: In this retrospective study, medical records of histopathologically confirmed LADC patients were reviewed for demographic and clinical data. The 18F-FDG PET/CT pSUVmax nSUVmax were calculated and analyzed for their relationships with EGFRm and ALKr using multiple regression analysis. RESULTS: The study population consisted of 732 LADC patients with a mean age of 63±10 years. The frequencies of EGFRm and ALKr were 10.4% and 3.6%, respectively. Female gender, being a former- or never-smoker for EGFRm and age for ALKr were determined as independent risk factors (P<0.05). No significant differences in pSUVmax and nSUVmax were present between the patients with either EGFRm or ALKr compared to the wild-type genotype patients (P>0.05). CONCLUSION: We conclude that 18F-FDG PET/CT semi-quantitative parameter SUVmax could not be validated for the prediction of the EGFRm or the ALKr in our large series of 732 Turkish patients with LADC.

Female Patients with Small Cell Lung Cancer Have Better Survival than Males with Extensive but Not Limited Disease.

INTRODUCTION: Several previous studies have explored whether sex has prognostic significance in patients with small cell lung cancer (SCLC). In this retrospective study, we aimed to show the clinical significance of sex in SCLC patients. METHODS: A total of 378 SCLC patients were assessed retrospectively. RESULTS: Sixty-one (16.1%) patients were women; 26 of 131 (19.9%) patients had limited disease (LD-SCLC); and 14.2% of patients (35 of 247 patients) had extended disease (ED-SCLC). In all SCLC patients, regardless of stage, female patients were more likely to be nonsmokers (7.7 vs. 1%, p = 0.04 for LD-SCLC; and 11.4 vs. 1.4%, p = 0.001 for ED-SCLC) and more often to be anemic (26.9 vs. 11.4%, p = 0.04 for LD-SCLC; and 45.7 vs. 28%, p = 0.03 for ED-SCLC). While women with LD-SCLC were diagnosed younger (<60) than men (65.4 vs. 37.1%, p = 0.009), they had larger (>5 cm) tumors (69.2 vs. 42.9%, p = 0.01). Moreover, obesity (77.1 vs. 56.4%, p = 0.02) and less weight loss (88.6 vs. 73.6%, p = 0.04) were more common in women with ED-SCLC than in men. However, there were no associations between sex and significant prognostic factors, such as performance status, metastasis site, serum LDH level, response to chemotherapy, and disease recurrence. Outcomes in LD-SCLC patients were found to be similar between sexes; median overall survivals in women compared to men was 18 versus 15 months, respectively (p = 0.8). On the other hand, female patients with ED-SCLC had better survivals; median survivals for women versus men were 10 versus 7 months, respectively (p = 0.008). This significance for female ED-SCLC patients was also maintained in the multivariate analysis (p = 0.001). CONCLUSION: While the survival rates of female patients, who constitute a small proportion of SCLC patients, are no different from men in LD-SCLC, they are better in ED-SCLC.

Timing of chemotherapy after diagnosis of small cell lung cancer.

Systemic chemotherapy is the backbone of therapeutic management in small cell lung cancer (SCLC) and delay of treatment may lead to adverse patient outcomes. This study was conducted to determine the time elapsed between pathological diagnosis and initiation of chemotherapy in SCLC patients and to evaluate its clinical significance. A total of 323 pathologically confirmed SCLC patients were enrolled in the study and analyzed retrospectively. The median value of the patients' time to treatment was used as the cut-off value in distinguishing between early and late chemotherapy. The median (range) of the time interval between the pathological diagnosis and the initiation of chemotherapy was 18 days (1-257). Compared with other clinical variables, only the performance status of patients was significantly associated with the time from diagnosis to initiation of chemotherapy; patients with poor prognostic factors received chemotherapy earlier than other patients (32.9 vs 18.9%, p = 0.004, and 14.5 vs 19 days, p = 0.006). Although patients who received early treatment were found to live less, there was no statistically significant difference in overall survival in patients according to the timing of chemotherapy administration (p = 0.08). In conclusion, there are controversial results about the timing of chemotherapy administration to SCLC patients. More standardized definitions and guides for calculation of the time interval between diagnosis and treatment are needed to better understand the delays in the treatment of patients with clinically rapidly disseminating SCLC.

Clinical significances of TTF-1, neuroendocrine (chromogranin, synaptophysin, CD56), and keratin (pancytokeratin, CK7, CK5/6) marker immunostaining in small cell lung cancer.

PURPOSE: Immunohistochemistry (IHC) markers have established a role in the pathological diagnosis of small cell lung cancer (SCLC) and especially neuroendocrine markers help to differentiate SCLC from other tumors. The study aimed to evaluate the clinical role of different IHC markers in SCLC patients. METHODS: A total of 378 SCLC patients were enrolled in the study and analyzed retrospectively. TTF-1, neuroendocrine markers (chromogranin, synaptophysin, and CD56), and keratin markers (pancytokeratin, CK7 and CK5/6) were assessed. RESULTS: CD56 had the highest expression (92.3%) followed by pancytokeratin (82.8%), TTF-1 (74.8%), synaptophysin (72.7%), chromogranin (55.6%), CK7 (54.8%), and CK5/6 (9%). No differences were observed in the expression of all markers according to the stage of the disease. Extended disease SCLC (ED-SCLC) patients with synaptophysin expression had a higher response to chemotherapy compared to those without staining (p = 0.01); on the other hand, the chemotherapy response of these patients was not significantly different when they expressed CK7 (p = 0.06). Pancytokeratin expression was associated with favorable survival in both limited disease SCLC (LD-SCLC) (p = 0.02) and ED-SCLC (p = 0.005) patients. Similarly, ED-SCLC patients with CD56 staining lived longer than those without expression (p = 0.001). The lack of synaptophysin expression in LD-SCLC patients (p = 0.06) and TTF-1 expression in ED-SCLC patients (p = 0.06) were correlated with better survival rates. CONCLUSION: We conclude that IHC markers, used frequently in the diagnosis of SCLC, might also be used in clinical decision-making, since they are correlated with predictive and prognostic factors for the disease.

Prognostic significance of body mass index and serum albumin as the indicators of nutritional status in small cell lung cancer.

BACKGROUND: Body mass index (BMI) and serum albumin (ALB) level are long-established markers that reflect the nutritional status and eventually the prognosis of cancer patients. The objective of the study was to determine the clinical significance of these factors and specify their roles in outcomes compared with performance status (PS) and weight loss (WL), which are considered the most significant patient-related prognostic factors in small cell lung cancer (SCLC) treated with platinum-etoposide-based chemotherapy. METHODS: A total of 378 patients with SCLC were enrolled in the study and analyzed retrospectively. RESULTS: BMI values were similar by clinical stage, whereas the percentages of the patients with WL, low serum ALB, and particularly poor (≥2) PS were significantly higher in patients with extended disease SCLC (ED-SCLC) compared to those with limited disease SCLC (LD-SCLC). In LD-SCLC, patients with poor PS lived for a significantly shorter time than patients with good PS (HR: 7.791, p = 0.0001); however, BMI (HR: 1.035, p = 0.8), WL (HR: 0.857, p = 0.5), and ALB (HR: 0.743, p = 0.3) had no significant effect on the outcome. In ED-SCLC, PS (HR: 4.257, p = 0.0001), WL (HR: 1.677, p = 0.001), and ALB (HR: 0.680, p = 0.007) had an impact on survival, but BMI did not (HR: 0.791, p = 0.08). In LD-SCLC, the univariate analysis showed that only poor PS was correlated with increased mortality (HR: 7.791, p = 0.0001); yet it lost significance in multivariate analysis. In ED-SCLC, poor PS (HR: 4.257, p = 0.0001), WL (HR: 1.667, p = 0.001), and a low ALB level (HR: 0.680, p = 0.007) were shown to be factors for poor prognosis in the univariate analysis; yet only PS remained significant in multivariate analysis (HR: 2.286, p = 0.001). CONCLUSION: Even though BMI and serum albumin showed no prognostic value in SCLC patients treated with chemotherapy, PS was found to be the most significant prognostic factor in both LD- and ED-SCLC stages.

The Impact of Complex Loadings on the Structure of the L2-L3 Intervertebral Disc in a Sheep Spine Cadaver Model: A Biomechanical and Histological Evaluation.

Background The human vertebral column generates movements under versatile, dynamic loads. Understanding how the spine reacts to these movements and loads is crucial for developing new spine implants and surgical treatments for intervertebral disc injuries. Mechanically uni-axial compression models have been extensively studied. However, the spine's daily loading is not limited to compression, so it is crucial to measure its behavior in all movements (flexion-extension, rotation, and axial compression). Methods This study utilized L1-L5 segments from 19 healthy adult sheep spines. The L2-L3 disc of the first spine underwent only histological evaluation without biomechanical testing to define basic histological parameters. The remaining 18 were divided into three groups of six and subjected to biomechanical tests. Different mechanisms for three groups of spinal segments were prepared, and tests were performed on Shimadzu AG-IS 10 KN (Universal Drawing Press, Kyoto, Japan). An axial load (800 N) was applied to the first group, an axial load with 15 degrees of flexion to the second group, and an axial load with 10 degrees of rotation plus 15 degrees of flexion to the third group. A biomechanical evaluation of the maximum elongation amounts (MEAs) was performed and compared between the groups. Then, the L2-L3 discs were removed from the sheep spines, and a histological examination of the discs was conducted using Hematoxylin-Eosin (HE), Alcian Blue (AB), and Masson's Trichrome (MT) staining. Results The mean MEA ± Standard Deviation (Range) was 1.39 ± 0.38 (0.91-1.94) for Group 1, 2.02 ± 0.75 (0.91-3.01) for Group 2, and 2.47 ± 1.09 (0.64-3.9) for Group 3. Biomechanically, although MEAs increased from Group 1 to Group 3 (meaning that the mean MEAs increased as the number of types of applied force increased), there was no statistically significant difference between the groups regarding the MEAs (P = 0.092). Histologically, no significant differences were observed between all groups after HE staining. In all groups, hypercellularity, edema in the connective tissue, separation between tissue layers, delamination, and signs of swelling and necrosis in the cells were observed similarly. For the AB staining, there was a decrease in the glycosaminoglycan (GAG) structure in the tissue samples compared to the control tissue, but no significant differences were observed between the groups. However, it was observed that the stratification in Group 3 was slightly more deteriorated than in the other groups. For the MT staining, collagen structure deterioration was observed in all groups. It was observed that the amount of collagen was significantly reduced compared to the control tissue. Conclusion As a result, when the axial load is applied biomechanically, there is more displacement of the vertebral discs in Group 3 with multidimensional movements. Furthermore, histological studies revealed deterioration between tissue layers when exposed to complex movements, and the degradation of stratification in group 3 compared to other loading combinations in groups 2 and 3 may indicate the role of complex loads in the formation of disc herniation.

A multicenter, retrospective archive study of radiological and clinical features of ALK-positive non-small cell lung cancer patients and crizotinib efficacy.

To evaluate radiological and clinical features in metastatic anaplastic lymphoma kinase+ non-small cell lung cancer patients and crizotinib efficacy in different lines. This national, non-interventional, multicenter, retrospective archive screening study evaluated demographic, clinical, and radiological imaging features, and treatment approaches in patients treated between 2013-2017. Totally 367 patients (54.8% males, median age at diagnosis 54 years) were included. Of them, 45.4% were smokers, and 8.7% had a family history of lung cancer. On radiological findings, 55.9% of the tumors were located peripherally, 7.7% of the patients had cavitary lesions, and 42.9% presented with pleural effusion. Pleural effusion was higher in nonsmokers than in smokers (37.3% vs. 25.3%, P = .018). About 47.4% of cases developed distant metastases during treatment, most frequently to the brain (26.2%). Chemotherapy was the first line treatment in 55.0%. Objective response rate was 61.9% (complete response: 7.6%; partial response: 54.2%). The highest complete and partial response rates were observed in patients who received crizotinib as the 2nd line treatment. The median progression-free survival was 14 months (standard error: 1.4, 95% confidence interval: 11.2-16.8 months). Crizotinib treatment lines yielded similar progression-free survival (P = .078). The most frequent treatment-related adverse event was fatigue (14.7%). Adrenal gland metastasis was significantly higher in males and smokers, and pleural involvement and effusion were significantly higher in nonsmokers-a novel finding that has not been reported previously. The radiological and histological characteristics were consistent with the literature data, but several differences in clinical characteristics might be related to population characteristics.

Treatment outcomes and prognostic factors in patients with driver mutant non-small cell lung cancer and de novo brain metastases.

Central nervous system (CNS) metastases can be seen at a rate of 30% in advanced stages for patients with non-small cell lung cancer (NSCLC). Growing evidence indicates the predictive roles of driver gene mutations in the development of brain metastases (BM) in recent years, meaning that oncogene-driven NSCLC have a high incidence of BM at diagnosis. Today, 3rd generation targeted drugs with high intracranial efficacy, which can cross the blood-brain barrier, have made a positive contribution to survival for these patients with an increased propensity to BM. It is important to update the clinical and pathological factors reflected in the survival with real-life data. A multi-center, retrospective database of 306 patients diagnosed with driver mutant NSCLC and initially presented with BM between between November 2008 and September 2022 were analyzed. The median progression-free survival (mPFS) was 12.25 months (95% CI, 10-14.5). While 254 of the patients received tyrosine kinase inhibitor (TKI), 51 patients received chemotherapy as first line treatment. The median intracranial PFS (iPFS) was 18.5 months (95% CI, 14.8-22.2). The median overall survival (OS) was 29 months (95% CI, 25.2-33.0). It was found that having 3 or less BM and absence of extracranial metastases were significantly associated with better mOS and iPFS. The relationship between the size of BM and survival was found to be non-significant. Among patients with advanced NSCLC with de novo BM carrying a driver mutation, long-term progression-free and overall survival can be achieved with the advent of targeted agents with high CNS efficacy with more conservative and localized radiotherapy modalities.

Frequency of fibromyalgia in a cohort of Turkish patients with lung cancer and its effect on pain, sleep quality, fatigue and quality of life.

This study aimed to examine the frequency of fibromyalgia (FM) in patients with lung cancer and evaluate its effect on patients' pain, sleep quality, fatigue, and quality of life parameters. The study was designed as a prospective cross-sectional and a total of 116 lung cancer patients were included. FM classification was made according to the 2016 ACR criteria. All patients were evaluated using a visual analog scale, fibromyalgia impact questionnaire, multidimensional assessment of fatigue, EuroQol 5D scale, Jenkins sleep scale, and Beck depression inventory. Patients were divided into FM-positive and negative groups according to the presence of FM. Demographic and clinical parameters were investigated between the groups. FM was detected in 14 (12.2%) patients. The mean age of the patients was 62.2 ±â€…8.4 years. There was a male predominance in 93 (80.2%) patients. No statistical difference was found between the groups in terms of body mass index, age, symptom duration, chemotherapy, and radiotherapy history. A statistically significant difference was found between FM positive and negative groups in FIQ, multidimensional assessment of fatigue, JSS, EQ-5D, visual analog scale, and Beck depression inventory scores. FM is seen more frequently in patients with lung cancer and has a negative effect on sleep, quality of life, fatigue, and mental functions. We think that physicians should not ignore the presence of FM when treating patients diagnosed with lung cancer.

Primary tumor SUVmax and ratio of SUVmax to primary tumor size on pretreatment 18F-FDG-PET/CT scan in small cell lung cancer : Which is superior for the prognosis?

BACKGROUND: The prognostic impact of tumor SUVmax (t-SUVmax) in small cell lung cancer (SCLC) has been questioned with controversial results, and the significance of the ratio of tumor SUVmax to primary tumor size (SUVmax/t-size) in SCLC has yet to be clarified as well. In this study, a retrospective analysis was carried out to figure out the prognostic and predictive powers of pretreatment primary t­SUVmax and t­SUVmax/t-size ratio in patients with SCLC. METHODS: A total of 349 SCLC patients who underwent pretreatment staging with PET/CT scan were enrolled in the study and analyzed retrospectively. RESULTS: In limited disease SCLC (LD-SCLC), tumor size was significantly associated with both t­SUVmax (p = 0.02) and t­SUVmax/t-size (p = 0.0001). Furthermore, performance status, tumor size (p = 0.001), and liver metastasis were significantly associated with t­SUVmax in extended disease SCLC (ED-SCLC). Moreover, tumor size (p = 0.0001), performance status, cigarette smoking history, and pulmonary/pleural metastasis were found to be correlated with t­SUVmax/t-size. No associations were found between clinical stages and either t­SUVmax or t­SUVmax/t-size (p = 0.9 for both), and t­SUVmax and t­SUVmax/t-size values were found to have similar survival rates in both LD-SCLC and ED-SCLC patients. In univariate and multivariate analyses, both t­SUVmax and t­SUVmax/t-size were found not to be associated with overall survival (p > 0.05) CONCLUSION: This study does not advocate the use of either t­SUVmax or t­SUVmax/t-size on pretreatment 18F­FDG-PET/CT scan as prognostic and predictive tools for both LD-SCLC and ED-SCLC patients. Likewise, we did not find that t­SUVmax/t-size was superior to t­SUVmax in that respect.

Neither the presence nor the severity of hyponatremia affected the outcome of the patients with small cell lung cancer.

BACKGROUND: Hyponatremia is the most common electrolyte disorder in lung cancer, and it particularly occurs in small cell lung cancer (SCLC) patients. The prognostic significance of hyponatremia has been reported in several studies with controversial results. AIMS: We aimed in this study to investigate hyponatremia and evaluate its prognostic value in SCLC patients. METHODS: The data of 373 SCLC patients were analyzed retrospectively. Serum sodium concentrations were measured from blood samples taken from all patients before treatment. Hyponatremia was defined as a serum sodium concentration below 135 mmol/L and then assigned into two groups: mild (130 to 134 mmol/L) and severe (below ≤ 129 mmol/L) hyponatremia. RESULTS: Hyponatremia was detected in 85 (22.8%) patients (mild hyponatremia in 51 (13.7%) and severe hyponatremia in 34 (9.1%) patients). Furthermore, 26% (63 of 242) of ED-SCLC patients and 16.8% (22 of 131) of LD-SCLC patients had hyponatremia. While no clinical parameter was statistically associated with serum sodium concentrations in LD-SCLC patients, hyponatremic ED-SCLC patients were more frequently associated with weight loss (p = 0.04) and liver metastasis (p = 0.04). In LD-SCLC, the overall survival (OS) rates of patients with hyponatremia were similar to those with normonatremia (p = 0.6). Likewise, hyponatremic and normonatremic ED-SCLC patients had similar life expectancies (p = 0.1). Moreover, the severity of hyponatremia did not affect OS in either LD-SCLC (p = 0.3) or ED-SCLC (p = 0.1). CONCLUSION: Serum sodium concentration did not have an impact on survival in SCLC patients; thus, we concluded that neither the presence nor the severity of hyponatremia affected the outcome of these patients.

Is there any prognostic significance in pleural involvement and/or effusion in patients with ALK-positive NSCLC?

PURPOSE: Anaplastic lymphoma kinase (ALK) mutations occurs in approximately 3-5% of patients with non-small cell lung cancer (NSCLC). Pleural involvement/effusion is common in ALK-positive patients with NSCLC at baseline. The aim of the study was to evaluate the characteristics of ALK-positive patients who have Ple-I/E. METHODS: In this multicenter study, patients with ALK-positive NSCLC who have Ple-I/E were retrospectively analyzed. Clinical and demographic characteristics of the disease, response rates, median progression-free survival (PFS), and overall survival (OS) were evaluated in 362 ALK-positive patients with NSCLC. RESULTS: Of the patients, 198 (54.7%) were male. The median age at the time of diagnosis was 54 (range 21-85) years. All patients' histology was adenocarcinoma (100%). At baseline, 57 (15.7%) patients had Ple-I/E. There was no association between Ple-I/E and gender, lung metastasis, or distant lymphadenopathy (LAP) metastasis. The frequencies of liver, brain, and bone metastases were significantly higher in ALK-positive patients without Ple-I/E compared to those with Ple-I/E (respectively 18.2% vs 4.8%, p = 0.008; 19.1% vs 4.8%, p = 0.001; 20.6% vs 8.9%, p = 0.002). The median PFS was longer in ALK-positive patients who had Ple-I/E (18.7 vs 10.6 months, p = 0.017). Similarly, the median OS was longer in ALK-positive patients who had Ple-I/E (44.6 vs 22.6 months, p = 0.051). CONCLUSION: Brain, liver, and bone metastases were lower in ALK-positive patients with Ple-I/E. Patients presented with Ple-I/E were prone to have better PFS and OS.

Real-life comparison of afatinib and erlotinib in non-small cell lung cancer with rare EGFR exon 18 and exon 20 mutations: a Turkish Oncology Group (TOG) study.

OBJECTIVES: To compare the survival of first- and second-generation tyrosine kinase inhibitors (TKIs) in patients with rare EGFR exon 18 and exon 20 mutation-positive non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We retrospectively evaluated survival characteristics of 125 patients with EGFR exon 18 and exon 20 mutated NSCLC who received erlotinib or afatinib as first line treatment between 2012 and 2021 from 34 oncology centres. Since exon 20 insertion is associated with TKI resistance, these 18 patients were excluded from the study. RESULTS: EGFR exon 18 mutations were seen in 60%, exon 20 mutations in 16%, and complex mutations in 24% of the patients with NSCLC who were evaluated for the study. There were 75 patients in erlotinib treated arm and 50 patients in afatinib arm. Patients treated with erlotinib had progression-free survival time (PFS) of 8.0 months and PFS was 7.0 months in the afatinib arm (p = 0.869), while overall survival time (OS) was 20.0 vs 24.8 months, respectively (p = 0.190). PFS of exon 18 mutated arm was 7.0 months, exon 20 mutated arm was 4.3 months, and complex mutation positive group was 17.3 months, and this was statistically significant (p = 0.036). The longest OS was 32.5 months, seen in the complex mutations group, which was not statistically different than exon 18 and in exon 20 mutated groups (21.0 and 21.2 months, respectively) (p = 0.323). CONCLUSION: In this patient group, especially patients with complex mutations are as sensitive to EGFR TKI treatment similar to classical mutations, and in patients with rare exon 18 and exon 20 EGFR mutation both first- and second-generation EGFR-TKIs should be considered, especially as first- and second-line options.

The effect of sarcopenia on erlotinib therapy in patients with metastatic lung adenocarcinoma.

Erlotinib, a tyrosine kinase inhibitor, has been shown to improve the survival of patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer. Sarcopenia is a status with increasing importance in lung cancer, and it may predict a poor prognosis. We aimed to evaluate the impact of sarcopenia on erlotinib therapy and prognosis in patients with EGFR-mutated (exon 19 or 21 L858R) metastatic lung adenocarcinoma. Sarcopenia was defined as skeletal muscle index ≤39 cm2/m2 for women and ≤55 cm2/m2 for men. The patient characteristics, inflammation parameters, clinical and survival outcomes of the erlotinib therapy were examined according to sarcopenia status. We also analyzed the erlotinib treatment-related toxicity. Seventy-two patients were included in our retrospective study, and the mean age of the patients was 63.7 years. A total of 39 (54.2%) patients were diagnosed with sarcopenia. Patients with sarcopenia had a poor prognosis and had a shorter median progression-free survival (PFS) than patients without sarcopenia (10.5 months vs. 21.8 months, p=0.002). Sarcopenia (HR 2.08) and C-reactive protein > 6.5 mg/L (HR 2.57) were determined as independent poor prognostic factors for PFS of erlotinib therapy. Treatment-related toxicity occurred in 34.7% of patients treated with erlotinib, and sarcopenia did not significantly affect treatment-related toxicity. We also found that sarcopenia significantly affected the response to erlotinib. The expected survival outcomes may be low when erlotinib therapy is used in patients with sarcopenia and metastatic lung adenocarcinoma. This study showed that survival and clinical outcomes could be better predicted by detecting sarcopenia in patients with lung cancer using erlotinib.

Psychological impacts of COVID-19 pandemic in cancer patients on active treatment.

Introduction: Although cancer patients have a high risk of exposing COVID-19 and developing severe complications, they have to receive active treatment. We aimed to determine the psychological conditions of cancer patients and shed light on the establishment of early psychological intervention and intervention policies by making specific recommendations. Method: We consecutively evaluated 385 cancer patients under treatment. Post-traumatic stress disorder (PTSD) symptoms, depression, anxiety, stress, and associated sociodemographic/clinical characteristics were investigated. In addition, we applied depression-anxiety-stress-scale-21 (DASS-21) for the mental states of patients and Impact of Event-Scale-Revised (IES-R) for the psychological effects of Covid-19. Results: The mean age was 58 (18-88). 47.2% were psychologically distressful per DASS-21, and 39.3% were traumatic per IES-R scores. 71.9% stated the risk of getting COVID-19 was high since they had cancer, and 82% stated serious complications would develop if they had COVID-19 infection. Patients diagnosed for more than one year were more stressed, anxious, and depressive (p-value = 0.001,0.003,0.049, respectively). Singles were more stressed, depressed, and traumatized than couples (p-value = 0.001, 0.011, 0.001). In multivariate analysis, a significant correlation with being under psychiatric treatment before the pandemic was found for depression (OR: 3.743, 95 %CI: 1.790-7.827) anxiety (OR: 3.776-95 %CI: 1.945-7.332) and stress levels (OR: 4.129, 95 %CI: 1.728-9.866). Having relatives who died or received treatment for COVID-19(OR: 0.515,0.296-0.895) and being unmarried (OR: 2.445-95% CI: 1.260-4.747) predicts PTSD development. Conclusions: When the psychological effects of the COVID-19 pandemic are manifesting strongly, cancer patients' anxiety and exposure levels are high. It is of great importance that clinicians understand needs, recognize psychological distress, and direct them to relevant departments for supportive care.

The effect of paclitaxel plus carboplatin chemotherapy on subclinical cardiotoxicity in patients with non-small cell lung cancer: A speckle tracking echocardiography-based study.

BACKGROUND: Although chemotherapy-induced cardiotoxicity is an emerging problem, limited information is available on the effects of chemotherapy on left ventricular (LV) mechanical functions in patients with non-small cell lung cancer (NSCLC). OBJECTIVE: We aimed to explore chemotherapy-induced alterations in cardiac mechanical functions in patients with NSCLC using speckle tracking echocardiography (STE). METHODS: Seventy-one patients with NSCLC and 34 age and sex matched control subjects were consecutively included. Based on their good performance status (Eastern Cooperative Oncology Group performance status), 39 patients were treated with paclitaxel plus carboplatin (PC) regimen and 32 patients were treated with vinorelbine plus cisplatin (VC) regimen. All patients and controls underwent conventional two-dimensional echocardiography and STE at baseline to assess their LV functions. The echocardiographic examinations of NSCLC patients were repeated after the chemotherapy regimens. RESULTS: None of the NSCLC patients developed any signs or symptoms of clinical heart failure during or after the chemotherapy. There were not any significant differences in LV ejection fraction between NSCLC patients and controls before and after chemotherapy. There were not any significant differences in baseline LV global longitudinal strain (GLS), radial strain (RS), and circumferential strain (CS) between NSCLC patients and controls. However, all LV GLS, RS and CS significantly decreased in patients treated with the PC regimen resulting in a significant difference compared to both VC group and controls while no significant decreases were observed in strain measures in VC group. CONCLUSION: Paclitaxel plus carboplatin, but not VC, may induce subclinical cardiotoxicity in patients with NSCLC, which may be detected by STE.

Atezolizumab combined with chemotherapy in the first-line treatment of extensive-stage small cell lung cancer: a real-life data of the Turkish Oncology Group.

PURPOSE: Atezolizumab has been shown to be effective and safe in randomized trial in the first-line treatment of extensive-stage small cell lung cancer (SCLC). However, there are limited real-life data on atezolizumab. In this study, we aimed to determine the real-life efficacy and safety of atezolizumab combined with chemotherapy in the first-line treatment of extensive-stage SCLC. METHODS: This trial is a retrospective multicenter study of the Turkish Oncology Group, which included extensive-stage SCLC patients who received atezolizumab combined with chemotherapy in a first-line treatment. The characteristics of the patients, treatment and response rates, and PFS and OS are presented. Factors associated with PFS and OS were analyzed by univariate and multivariate analysis. RESULTS: A total of 213 patients at the 30 oncology centers were included. The median number of chemotherapy cycle was 5 (1-8) and atezolizumab cycle was 7 (1-32). After median 11.9 months of follow-up, median PFS and OS was 6.8 months (95%CI 5.7-7.8), and 11.9 months (95%CI 11-12.7), respectively. The ORR was 61.9%. ECOG-PS (p = 0.002) and number of metastatic sites (p = 0.001) were associated with PFS and pack-year of smoking (p = 0.05), while ECOG-PS (p = 0.03) and number of metastatic sites (p = 0.001) were associated with OS. Hematological side effects were common and toxicities were manageable. CONCLUSION: This real-life data confirm the efficacy and safety of atezolizumab in combination with chemotherapy in first-line treatment of extensive-stage SCLC.

IGFBP-4: A promising biomarker for lung cancer.

Background: Insulin-like growth factor binding protein-4 (IGFBP-4), a member of the insulin-like growth factor (IGF) family, transports, and regulates the activity of IGFs. The pregnancy-associated plasma protein-A (PAPP-A) has proteolytic activity towards IGFBP-4, and both proteins have been associated with a variety of cancers, including lung cancer. Thus, we aimed to evaluate the use of IGFBP-4 and PAPP-A as potential biomarkers for lung cancer. Methods: Eighty-three volunteers, including 60 patients with lung cancer and 23 healthy individuals, were included in this study. The patients with lung cancer were selected based on their treatment status, histological subgroup, and stage of the disease. Enzyme-linked immunosorbent assays were used to assess the serum levels of IGFBP-4 and PAPPA, whereas the IGF-1 levels were measured using a chemiluminescent immunometric assay. Results: The serum IGFBP-4 levels in all patient groups, regardless of the treatment status and histological differences, were significantly higher than those in the control group (p<0.005). However, the serum PAPP-A levels in the untreated patient group were found to be higher than those in the control group, but this difference was not statistically significant (p=0.086). Conclusions: The serum PAPP-A and IGFBP-4 levels are elevated in lung cancer. However, IGFBP-4 may have better potential than PAPP-A as a lung cancer biomarker.