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Purpose: Integrating moderate hypofractionation to the macroscopic tumor with elective nodal irradiation while sparing the organs at risk (OAR) in chemoradiotherapy of locally advanced non-small-cell lung cancer.Methods: From 2010-2018, treatment, patient and tumor characteristics of 138 patients from two radiation therapy centers were assessed. Chemoradiotherapy by intensity-modulated radiation therapy (IMRT) with a simultaneous integrated boost (SIB) to the primary tumor and macroscopic lymph node metastases was used.Results: A total of 124 (90%) patients received concurrent chemotherapy. 106 (76%) patients had UICC (Union for International Cancer Control) stage ≥IIIB and 21 (15%) patients had an oligometastatic disease (UICC stage IV). Median SIB and elective total dose was 61.6 and 50.4 Gy in 28 fractions, respectively. Furthermore, 64 patients (46%) had an additional sequential boost to the primary tumor after the SIB-IMRT main series: median 6.6 Gy in median 3 fractions. The median cumulative mean lung dose was 15.6 Gy (range 6.2-29.5 Gy). Median follow-up and radiological follow-up for all patients was 18.0 months (range 0.6-86.9) and 16.0 months (range 0.2-86.9), respectively. Actuarial local control rates at 1, 2 and 3 years were 80.4, 68.4 and 57.8%. Median overall survival and progression-free survival was 30.0 months (95% confidence interval [CI] 23.5-36.4) and 12.1 months (95% CI 8.2-16.0), respectively. Treatment-related toxicity was moderate. Radiation-induced pneumonitis grade 2 and grade 3 occurred in 13 (9.8%) and 3 (2.3%) patients.Conclusions: Chemoradiotherapy using SIB-IMRT showed promising local tumor control rates and acceptable toxicity in patients with locally advanced and in part oligometastatic lung cancer. The SIB concept, resulting in a relatively low mean lung dose, was associated with low numbers of clinically relevant pneumonitis. The overall survival appears promising in the presence of a majority of patients with UICC stage ≥IIIB disease. [ABSTRACT FROM AUTHOR]

Video-assisted thoracic surgery (VATS) has become widespread in the last 20 years, followed by robot-assisted thoracic surgery (RATS). Few studies compared the learning curve between RATS lobectomy and conventional VATS. This study included 79 RATS lobectomy cases performed in our hospital from November 2015 to October 2019. To estimate the required number for learning, the cumulative sum method, which is to plot a value obtained by sequentially accumulating a difference from a mean value was applied. As a result, the median total operative time and the median console time for all cases were 167 minutes and 138 minutes, respectively. Firstly, for our team, 28 cases were estimated to be required for learning curve for RATS lobectomy. For individual, each surgeon might be learned in only 5 to 6 cases. By contrast, the number of cases for learning VATS lobectomy which was underwent by a 'single' surgeon from 2009 was estimated to be 35 cases. The time to dock from start operation (median 14 minutes) reached plateau in 18 cases, but the time after rollout was median of 18 minutes and there was no significant change from the beginning. In conclusion, RATS lobectomy might be a technique that could be learned in a small number of cases compared to VATS. The results of this study might be helpful for certified surgeons who tried to get started with RATS and for establishing a learning program. [ABSTRACT FROM AUTHOR]

Aim: We report, herein, three cases of pleomorphic carcinoma of the lung treated with immune checkpoint inhibitors. Case 1: A 73-year-old man was diagnosed as having pleomorphic carcinoma of the lung and treated with pembrolizumab alone. However, he showed no response and died 4 months after the initiation of the treatment. Case 2: A 66-year-old man was diagnosed as having pleomorphic carcinoma of the lung. He was started on a combination regimen of pembrolizumab plus carboplatin plus nab-paclitaxel, and a remarkable response was observed. Case 3: A 49-year-old man was diagnosed as having pleomorphic carcinoma of the lung. He was started on pembrolizumab monotherapy as second-line treatment. Eleven months after the treatment initiation, computed tomography revealed the decrease of tumor diameter. Conclusion: Immune checkpoint inhibitor therapy is expected to improve the prognosis of patients with pleomorphic carcinoma of the lung. [ABSTRACT FROM AUTHOR]

Background: Time-to-treatment is defined as a quality indicator for cancer care but is not well documented. We investigated whether meeting Norwegian timeframes of 35/42 days from referral until start of chemotherapy or surgery/radiotherapy for lung cancer was associated with survival. Patients and Methods: The medical records of 439 lung cancer patients at a regional cancer center were reviewed and categorized according to treatment: (i) surgery; ii) radical radiotherapy; iii) stereotactic radiotherapy; iv) palliative treatment, no cancer symptoms; v) palliative treatment with severe cancer symptoms). Results: Proportions receiving timely treatment varied significantly at 39%, 48%, 10%, 44% and 89%, respectively (p<0.001). Overall, those starting treatment on time had the shortest median overall survival (10.6 vs. 22.6 months; p<0.001). This was also the case for palliative (5.3 vs. 11.4 months) (p<0.001) but not for curative treatment (not reached vs. 38.3 months) (p=0.038). Conclusion: Timely treatment is not necessarily associated with improved survival. [ABSTRACT FROM AUTHOR]

PURPOSE We sought to investigate the association between Medicaid expansion under the Affordable Care Act and access to stage-appropriate definitive treatment for breast, colon, non–small-cell lung, and prostate cancer for underserved racial and ethnic minorities and at minority-serving hospitals (MSHs). METHODS We conducted a retrospective, difference-in-differences study including minority patients with nonmetastatic breast, colon, non–small-cell lung, and prostate cancer and patients treated at MSHs between the age of 40 and 64, with tumors at stages eligible for definitive treatment from the National Cancer Database. We not only defined non-Hispanic Black and Hispanic cancer patients as racial and ethnic minorities but also report findings for non-Hispanic Black cancer patients separately. We examined the effect of Medicaid expansion on receipt of stage-appropriate definitive therapy, time to treatment initiation (TTI) within 30 days of diagnosis, and TTI within 90 days of diagnosis. RESULTS Receipt of definitive treatment for minorities in expansion states did not change compared with minority patients in nonexpansion states. The proportion of racial and ethnic minorities in expansion states receiving treatment within 30 days increased (difference-in-differences: 13.62%; 95% CI, 1.63 to 5.61; P < .001) compared with minority patients in nonexpansion states; there was no change for TTI within 90 days. Analysis focused on Black cancer patients yielded similar results. In analyses stratified by MSH status, there was no change in receipt of definitive therapy, TTI within 30 days, and TTI within 90 days when comparing MSHs in expansion states with MSHs in nonexpansion states. CONCLUSION In our cohort of cancer patients with treatment-eligible disease, we found no significant association between Medicaid expansion and changes in receipt of definitive treatment for breast, prostate, lung, and colon cancer for racial and ethnic minorities and at MSHs. Medicaid expansion was associated with improved TTI at the patient level for racial and ethnic minorities, but not at the facility level for MSHs. Targeted interventions addressing the needs of MSHs are still needed to continue mitigating national facility–level disparities in cancer outcomes. [ABSTRACT FROM AUTHOR]

Aims The study aimed to estimate the risk of cardiac events in immune checkpoint inhibitor (ICI)-treated patients with lung cancer or malignant melanoma. Methods and results The study included consecutive patients with lung cancer or malignant melanoma in 2011–17 nationwide in Denmark. The main composite outcome was cardiac events (arrhythmia, peri- or myocarditis, heart failure) or cardiovascular death. Absolute risks were estimated and the association of ICI and cardiac events was analysed in multivariable Cox models. We included 25 573 patients with lung cancer. Of these, 743 were treated with programmed cell death-1 inhibitor (PD1i) and their 1-year absolute risk of cardiac events was 9.7% [95% confidence interval (CI) 6.8–12.5]. Of the 13 568 patients with malignant melanoma, 145 had PD1i and 212 had cytotoxic T-lymphocyte-associated protein-4 inhibitor (CTLA-4i) treatment. Their 1-year risks were 6.6% (1.8–11.3) and 7.5% (3.7–11.3). The hazard rates of cardiac events were higher in patients with vs. without ICI treatment. Within 6 months from 1st ICI administration, the hazard ratios were 2.14 (95% CI 1.50–3.05) in patients with lung cancer and 4.30 (1.38–13.42) and 4.93 (2.45–9.94) in patients with malignant melanoma with PD1i and CTLA-4i, respectively. After 6 months, HRs were 2.26 (1.27–4.02) for patients with lung cancer and 3.48 (1.91–6.35) for patients with malignant melanoma and CTLA-4i. Conclusions Among patients with lung cancer and malignant melanoma, ICI treated had increased rates of cardiac events. The absolute risks were higher in these data compared with previous pharmacovigilance studies (e.g. 1.8% peri-/myocarditis 1-year risk). [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD), an established risk factor for lung cancer, remains largely undiagnosed and untreated before lung cancer surgery. We evaluated the effect of perioperative bronchodilator therapy on lung function changes in COPD patients who underwent surgery for non-small cell lung cancer (NSCLC). From a database including NSCLC patients undergoing lung resection, COPD patients were identified and divided into two groups based on the use of bronchodilator during the pre- and post-operative period. Changes in forced expiratory volume in 1 s (FEV1) and postoperative complications were compared between patients treated with and without bronchodilators. Among 268 COPD patients, 112 (41.8%) received perioperative bronchodilator, and 75% (84/112) were newly diagnosed with COPD before surgery. Declines in FEV1 after surgery were alleviated by perioperative bronchodilator even after adjustments for related confounding factors including surgical extent, surgical approach and preoperative FEV1 (adjusted mean difference in FEV1 decline [95% CI] between perioperative bronchodilator group and no perioperative bronchodilator group; − 161.1 mL [− 240.2, − 82.0], − 179.2 mL [− 252.1, − 106.3], − 128.8 mL [− 193.2, − 64.4] at 1, 4, and 12 months after surgery, respectively). Prevalence of postoperative complications was similar between two groups. Perioperative bronchodilator therapy was effective to preserve lung function, after surgery for NSCLC in COPD patients. An active diagnosis and treatment of COPD are required for surgical candidates of NSCLC. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy of microwave ablation (MWA) and MWA plus monochemotherapy in elderly patients with advanced non-small-cell lung cancer (NSCLC). Patients with advanced NSCLC aged ≥70 years were retrospectively enrolled. MWA was performed at the primary tumor site. The end points included progression-free survival (PFS), response to MWA and overall survival (OS). Fifty-four patients were enrolled; of these, 36 received monochemotherapy. Complete ablation was achieved in 42 patients (77.8%). The median PFS and OS were 4.9 months and 21.8 months, respectively. Univariate analyses showed that female patients had superior PFS (31.9 months [95% confidence interval (CI): 0.8–63.0]) vs. 5.0 months in male patients (95% CI: 2.0–8.0), p =.002). Female sex was associated with better OS (not reached vs. 10.8 months, 95% CI: 9.3–12.3, p =.003). Moreover, patients with primary tumor size <3.5 cm had better OS than those with tumor size ≥3.5 cm (not reached vs. 10.9 months, 95% CI: 8.2–13.6, p =.006). Multivariate analyses showed that no characteristics were independent prognostic factors of PFS, but sex and primary tumor size were independent prognostic factors of OS. MWA was effective in the treatment of elderly patients with advanced NSCLC. [ABSTRACT FROM AUTHOR]

To evaluate tumor blood flow using 15O-water positron emission tomography (PET) in patients with non-small cell lung cancer (NSCLC) before and after chemotherapy with bevacizumab, and to investigate the effects of bevacizumab on tumor blood flow changes and progression-free survival (PFS). Twelve patients with NSCLC were enrolled. Six patients underwent chemotherapy with bevacizumab and the other six without bevacizumab. 15O-water dynamic PET scans were performed within 1 week before the start of chemotherapy and within 1 week after the first day of chemotherapy. Tumor blood flow was analyzed quantitatively using a single one-tissue compartment model with the correction of pulmonary circulation blood volume and arterial blood volume via an image-derived input function. In the bevacizumab group, mean tumor blood flow was statistically significantly reduced post-chemotherapy (pre-chemotherapy 0.27 ± 0.14 mL/cm3/min, post-chemotherapy 0.18 ± 0.12 mL/cm3/min). In the no bevacizumab group, there was no significant difference between mean tumor perfusion pre-chemotherapy (0.42 ± 0.42 mL/cm3/min) and post-chemotherapy (0.40 ± 0.27 mL/cm3/min). In the bevacizumab group, there was a positive correlation between the blood flow ratio (tumor blood flow post-chemotherapy/tumor blood flow pre-chemotherapy) and PFS (correlation coefficient 0.94). Mean tumor blood flow decreases after bevacizumab administration and was positively correlated with longer PFS. [ABSTRACT FROM AUTHOR]

Background: There is currently insufficient information available on effective therapies that can be administered to patients with non‐small cell cancer (NSCLC) who develop resistance to epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs). However, sequential treatment via programmed death‐1 (PD‐1) blockade followed by EGFR‐TKI rechallenge is suggested to improve the therapeutic efficacy in such patients. Methods: A total of 75 patients with advanced NSCLC harboring sensitive EGFR mutations treated with afatinib, erlotinib, or gefitinib after EGFR‐TKI treatment failure were retrospectively analyzed. Among them, 13 patients were treated with EGFR‐TKI rechallenge immediately after the failure of PD‐1 blockade therapy (experimental group) and the remaining 62 patients did not receive PD‐1 inhibitor therapy before EGFR‐TKI rechallenge (control group). Blood samples were collected at two time points; before the initiation of anti‐PD‐1 therapy and at EGFR‐TKI rechallenge. Results: The objective response rates of EGFR‐TKI rechallenge in the experimental and control groups were 46.1% and 16.1%, respectively, with a significant difference (p = 0.026). In the experimental group, the median progression‐free survival (PFS) and overall survival (OS) after EGFR‐TKI rechallenge were 5.0 and 25.0 months, respectively, and no statistically significant difference in the percentage of lymphocytes before immune checkpoint inhibitor (ICI) therapy and EGFR‐TKIs was observed in patients with partial response (PR) and without PR after EGFR‐TKI rechallenge. In particular, the sequential treatment of PD‐1 blockade therapy followed by EGFR‐TKI rechallenge was consecutively repeated three times in two out of 13 patients in the experimental group, and EGFR‐TKI rechallenge consecutively for the third time yielded a PR without increased toxicities. Conclusions: EGFR‐TKI rechallenge immediately after PD‐1 blockade treatment was identified as an effective therapy for NSCLC patients with resistance to EGFR‐TKIs. [ABSTRACT FROM AUTHOR]

Stereotactic body radiotherapy (SBRT) applies high doses and requires advanced techniques to spare surrounding tissue in the presence of organ motion. In this work patient individual phase gating is investigated. We studied peripheral and central primary lung tumors. The internal target volume (ITV) was defined including different numbers of phases picked from a 4D Computed tomography (CT) defining the gating window (gw). Planning target volume (PTV) reductions depending on the gw were analyzed. A treatment plan was calculated on a reference phase CT (rCT) and the dose for each breathing phase was calculated and accumulated on the rCT. We compared the dosimetric results with the dose calculated when all breathing phases were included for ITV definition. GWs including 1 to 10 breathing phases were analyzed. We found PTV reductions up to 38.4%. The mean reduction of the lung volume receiving 20 Gy due to gating was found to be 25.7% for peripheral tumors and 16.7% for central tumors. Gating considerably reduced esophageal doses. However, we found that simple reduction of the gw does not necessarily influence the dose in a clinically relevant range. Thus, we suggest a patient individual definition of the breathing phases included within the gw. [ABSTRACT FROM AUTHOR]

Small cell lung cancer (SCLC) is classified as a high-grade neuroendocrine (NE) tumor, but a subset of SCLC has been termed "variant" due to the loss of NE characteristics. In this study, we computed NE scores for patient-derived SCLC cell lines and xenografts, as well as human tumors. We aligned NE properties with transcription factor-defined molecular subtypes. Then we investigated the different immune phenotypes associated with high and low NE scores. We found repression of immune response genes as a shared feature between classic SCLC and pulmonary neuroendocrine cells of the healthy lung. With loss of NE fate, variant SCLC tumors regain cell-autonomous immune gene expression and exhibit higher tumor-immune interactions. Pan-cancer analysis revealed this NE lineage-specific immune phenotype in other cancers. Additionally, we observed MHC I re-expression in SCLC upon development of chemoresistance. These findings may help guide the design of treatment regimens in SCLC. Ling Cai et al. used transcriptomic profiling data of healthy lung, patient-derived small cell lung cancer cell lines, xenografts, and primary tumors to examine a link between neuroendocrine (NE) signatures and immune gene expression. Their findings suggest that cell-autonomous immune gene repression is a shared feature between healthy and tumor cells of NE lineage and may influence tumor-immune cell interaction and response to immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Advances in curative treatment for breast, colorectal, NSCLC and prostate cancer have led to improvements in cancer survival. Cancer treatment and recovery time can vary depending on the recommended modalities and intensity of therapy. Our objective was to determine the current real world duration of curative treatments for the four common cancers.Methods: A retrospective review was completed of patients referred to BC Cancer from 2010 to 2016, ≤ 65 years old, newly diagnosed with stage I-III breast, colorectal, NSCLC or prostate cancer who received curative intent treatment. Information was collected on baseline characteristics, date of diagnosis, surgery, type, duration and intent of both radiotherapy and chemotherapy.Results: In total, 22,275 patients were included: 55.7% breast, 22.4% colorectal, 9.2% NSCLC, 12.7% prostate cancer. Stage I/II/III at diagnosis: breast 47.2/38.7/14.1%, colorectal 26.5/30.1/43.5%, NSCLC 46.5/18.1/35.4%, prostate 7.7/62.9/29.4%. Patients treated with definitive surgery only: breast 35.9%, colorectal 58%, NSCLC 52.2%, prostate 40.1%. The median duration of multimodality treatment was breast 24.6 weeks, colorectal 26.7 weeks, NSCLC 9.1 weeks, and prostate 6.0 weeks.Conclusions: Approximately half of patients who undergo curative cancer treatment require definitive radiotherapy or multimodality treatment. The median duration of therapy for the most commonly treated cancers ranged from 6.0-26.7 weeks. Multimodality curative treatment can be prolonged for selected cancers when accounting for the duration of adjuvant chemotherapy and radiotherapy and recovery time between modalities. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer-related deaths, worldwide. Non-small cell lung cancer (NSCLC) is the most prevalent lung cancer subtype. YAP and TAZ have been implicated in lung cancer by acting as transcriptional co-activators of oncogenes or as transcriptional co-repressors of tumor suppressor genes. Previously we reported that YAP and TAZ regulate microRNAs expression in NSCLC. Among the set of regulated miRNAs, the oncogenic miR-25, 93, and 106b, clustering within the MCM7 gene were selected for further studies. We firstly identified Transforming Growth Factor-β (TGF-β) Receptor 2 (TGFBR2), a member of the TGF-β signaling, as a target of the miRNA cluster, which exhibited prognostic value because of its tumor suppressor activity. We found that YAP/TAZ-mediated repression of TGFBR2 occurs both: post-transcriptionally through the miR-106b-25 cluster and transcriptionally by engaging the EZH2 epigenetic repressor that we reported here as a novel target gene of YAP/TAZ. Furthermore, we document that YAP/TAZ and EZH2 cooperate in lung tumorigenesis by transcriptionally repressing a specific subset of tumor suppressor genes, including TGFBR2. Our findings point to YAP/TAZ and EZH2 as potential therapeutic targets for NSCLC treatment. [ABSTRACT FROM AUTHOR]

Radiotherapy is a frequently used method for treatment of cancer which is regarded as one of the top two diseases causing premature death worldwide. However, radiotherapy is known to have many side effects. In this study, we evaluated biologically and histologically the possible protective effects of edaravone, the free radical scavenger and neuroprotective agent used to treat amyotrophic lateral sclerosis, on lung and small intestine against radiation-induced early side effects of 15 Gy total body irradiation in single fraction. Thirty-two rats were divided randomly into four equal groups. Groups were administered 15 Gy of external ionizing radiation to the whole body after 30 minutes of EDA administration (a dose of 500 and 50 mg/kg). Rats were sacrified at 72 h of the experiment. Tissues were separated to investigate levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPX) and malondialdehyde (MDA); and evealuate histopathological changings. The protective effect of EDA showed statistically significant in MDA, SOD and GSHPX values of lungs except CAT and statistically significant effect was observed in MDA in small intestine. Also, we showed statistically significant values with histopathological changings. Pediatric cancer patients who have a longer life expectancy are as important as their recovery from their normal life. We are expecting that EDA as a modulator of free radical scavenging pathways in many organs can reduce the side effects of radiation damage on lungs and small intestine. [ABSTRACT FROM AUTHOR]

At diagnosis, <1% of patients with non-small cell lung cancer (NSCLC) have synchronous solitary brain metastasis (SSBM). In prior cohorts without 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) staging, definitive treatment to intracranial and intrathoracic disease showed a 5-year overall survival (OS) of 11–21%. We investigated the long-term survival outcomes for patients with SSBM NSCLC, diagnosed in the FDG-PET/CT era and treated definitively with local therapies to both intracranial and intrathoracic sites of disease. This retrospective study assessed patients staged with FDG-PET/CT who received definitive lung and SSBM treatment from February 1999 to December 2017. A lung-molecular graded prognostic assessment (lung-molGPA) score was assigned for each patient using age, performance status score, and, where carried out, molecular status. Overall survival and progression-free survival (PFS) were calculated using Kaplan–Meier methods. Cox proportional hazard models determined OS and PFS prognostic factors. Forty-nine patients newly diagnosed with NSCLC and SSBM had a median age of 63 years (range 34–76). The median follow-up of all patients was 3.9 years. Thirty-three patients (67%) had ≥T2 disease, 23 (47%) had ≥N2. At 2 years, 45% of first failures were intracranial only (95% confidence interval 30–59). At 3 and 5 years, OS was 45% (95% confidence interval 32–63) and 30% (95% confidence interval 18–51), respectively. In ≥N1 disease, 5-year OS was 34% (95% confidence interval 18–63). The 3- and 5-year PFS was 8% (95% confidence interval 3–22) and 0%, respectively. Higher lung-molGPA was associated with longer OS (hazard ratio 0.26, 95% confidence interval 0.11–0.61, P = 0.002). Higher lung-molGPA (hazard ratio 0.33, 95% confidence interval 0.15–0.71, P = 0.005) and lower N-stage (hazard ratio 1.56, 95% confidence interval 1.13–2.15, P = 0.007) were associated with longer PFS. Definitive treatment of patients with NSCLC and SSBM staged with FDG-PET/CT can result in 5-year survivors, including those with ≥N1 disease. • Patients in this study had contemporary imaging with brain MRI and whole-body FDG-PET/CT. • Appropriate selection of patients presenting with solitary brain metastases for definitive treatment of the lung and brain was associated with a favourable 5-year overall survival. • Prolonged overall survival was also noted in those patients with >N1 disease. • Highlights the need for future prospective studies to guide the management of patients with oligometastatic NSCLC. [ABSTRACT FROM AUTHOR]

Patients with nonsmall cell lung cancer and limited metastatic disease have been defined as oligometastatic if local ablative therapy of all lesions is amenable. Evidence from different clinical retrospective series suggests that this subgroup harbours better prognosis than other stage IV patients. However, most reports have included patients with inconsistent numbers of metastases in different locations treated by a variety of invasive and noninvasive therapies. As long as further results from randomised clinical trials are awaited, treatment decision follows an interdisciplinary debate in each individual case. Surgery and radiotherapy should capture a dominant role in the treatment course offering the option of a curative-intended local therapy in combination with a systemic therapy based on an interdisciplinary decision. This review summarises the current treatment standard in oligometastatic lung cancer with focus on an ablative therapy for both lung primary and distant metastases in prognostically favourable locations. [ABSTRACT FROM AUTHOR]

Lung cancer is the most lethal cancer: it has a significant incidence and low survival rates. Lifestyle has an important influence on cancer onset and its progression, indeed environmental factors and smoke are involved in cancer establishment, and in lung cancer. Physical activity is a determinant in inhibiting or slowing lung cancer. Certainly, the inflammation is a major factor responsible for lung cancer establishment. In this scenario, regular physical activity can induce anti-inflammatory effects, reducing ROS production and stimulating immune cell system activity. On lung function, physical activity improves lung muscle strength, FEV1 and forced vital capacity. In lung cancer patients, it reduces dyspnea, fatigue and pain. Data in the literature has shown the effects of physical activity both in in vivo and in vitro studies, reporting that its anti-inflammatory action is determinant in the onset of human diseases such as lung cancer. It has a beneficial effect not only in the prevention of lung cancer, but also on treatment and prognosis. For these reasons, it is retained as an adjuvant in lung cancer treatment both for the administration and prognosis of this type of cancer. The purpose of this review is to analyze the role of physical activity in lung cancer and to recommend regular physical activity and lifestyle changes to prevent or treat this pathology.

The limitations of cisplatin, a standard chemotherapy for lung cancer, have been documented with serious adverse effects and drug resistance. To address the need for novel therapy, this study firstly reveals the potential of peptide from Lentinus squarrosulus (Mont.) as a chemotherapeutic adjuvant for cisplatin treatment. The purified peptide from L. squarrosulus aqueous extracts was obtained after eluting with 0.4 M NaCl through FPLC equipped with anion exchange column. Preincubation for 24 h with 5 µg/mL of the peptide at prior to treatment with 5 µM cisplatin significantly diminished %cell viability in various human lung cancer cells but not in human dermal papilla and proximal renal cells. Flow cytometry indicated the augmentation of cisplatin-induced apoptosis in lung cancer cells pretreated with peptide from L. squarrosulus. Preculture with the peptide dramatically inhibited colony formation in lung cancer cells derived after cisplatin treatment. Strong suppression on integrin-mediated survival was evidenced with the diminution of integrins (β1, β3, β5, α5, αV) and down-stream signals (p-FAK/FAK, p-Src/Src, p-Akt/Akt) consequence with alteration of p53, Bax, Blc-2 and Mcl-1 in cisplatin-treated lung cancer cells preincubated with peptide from L. squarrosulus. These results support the development of L. squarrosulus peptide as a novel combined chemotherapy with cisplatin for lung cancer treatment. [ABSTRACT FROM AUTHOR]

Background: This study compared a co‐ablation (CA) system, which is a novel ablation device, with an argon‐helium cryoablation (AHC) system. We aimed to compare the efficacy and safety of CA and AHC for the treatment of stage III–IV non‐small cell lung cancer (NSCLC). Methods: We conducted a multicenter randomized controlled trial (RCT) to determine whether CA was noninferior to AHC. The primary efficacy endpoints were the iceball coverage rate (ICR) and the disease control rate (DCR) one month after treatment. Noninferiority was declared if the lower limit of two‐sided 95% confidence interval (CI) was less than 10%. The ICR and DCR were identified by logistic regression. Treatment safety was assessed. Results: A total of 81 patients underwent randomization (41 assigned to the CA and 40 assigned to the AHC groups)and transthoracic ablation. The ICRs in the CA and AHC groups were 99.24% ± 2.18% and 98.66% ± 3.79%, respectively. Central lesions were associated with an increased risk of an incomplete ICR. The DCRs in the CA and AHC groups were 97.6% and 95%, respectively. A smaller lesion area in the CA group was significantly correlated with a better DCR. The rate of complications was 29.26% in the CA group and 30% in the AHC group. (P = 0.943). There was less probe usage per patient in the CA group. Conclusions: We determined that CA is noninferior to AHC in terms of efficacy and safety for the treatment of stage III–IV NSCLC. A smaller lesion area in the CA group was significantly correlated with a better DCR. Key points: CA was noninferior to AHC for stage III–IV NSCLC. [ABSTRACT FROM AUTHOR]

Background: Stereotactic Body Radiation Therapy (SBRT) is an innovative modality based on high precision planning and delivery. Cancer with bone metastases and oligometastases are associated with an intermediate or good prognosis. We assume that prolonged survival rates would be achieved if both the primary tumor and metastases are controlled by local treatment. Our purpose is to demonstrate, via a multicenter randomized phase III trial, that local treatment of metastatic sites with curative intent with SBRT associated of systemic standard of care treatment would improve the progression-free survival in patients with solid tumor (breast, prostate and non-small cell lung cancer) with up to 3 bone-only metastases compared to patients who received systemic standard of care treatment alone.Methods: This is an open-labeled randomized superiority multicenter phase III trial. Patients with up to 3 bone-only metastases will be randomized in a 1:1 ratio.between Arm A (Experimental group): Standard care of treatment & SBRT to all bone metastases, and Arm B (Control group): standard care of treatment. For patients receiving SBRT, radiotherapy dose and fractionation depends on the site of the bone metastasis and the proximity to critical normal structures. This study aims to accrue a total of 196 patients within 4 years. The primary endpoint is progression-free survival at 1 year, and secondary endpoints include Bone progression-free survival; Local control; Cancer-specific survival; Overall survival; Toxicity; Quality of life; Pain score analysis, Cost-utility analysis; Cost-effectiveness analysis and Budget impact analysis.Discussion: The expected benefit for the patient in the experimental arm is a longer expectancy of life without skeletal recurrence and the discomfort, pain and drastic reduction of mobility and handicap that the lack of local control of bone metastases eventually inflicts.Trials Registration: ClinicalTrials.gov NCT03143322 Registered on May 8th 2017. Ongoing study. [ABSTRACT FROM AUTHOR]

La radiothérapie stéréotaxique pulmonaire est réalisée dans l'équipe du centre Georges-François-Leclerc (CGFL) à Dijon depuis 2008 sur un accélérateur Truebeam® (Varian®) avec la technique RPM. Cinquante patients atteints d'un cancer bronchique primitif de stade T1–T2 (n = 30) ou une métastase bronchique (n = 20) ont été inclus dans l'étude. Depuis 2014, trois scanographies quadridimensionnelles successives à j1, j2 et j3, sont réalisées afin de s'assurer de la reproductibilité des ITV (Internet Target Volume). Les trois ITV sont délinéés (ITV 1,2 et 3) à partir de la MIP (Maximum Intensity Projection) de chacune des trois scanographies. Un ITV global est créé à partir des ITV des trois scanographies (fusion des MIP2 et 3 avec la MIP1). Une CBCT (Cone Beam Computerised Tomography) est réalisée au début de chaque séance d'irradiation pour positionner le patient. L'étude consistait à analyser la pertinence de la réalisation de trois scanographies différentes avant la dosimétrie pour définir l'ITV et à comparer les volumes délinéés sur les différentes CBCT à l'ITV pour s'assurer que le volume tumoral est bien inclus dans l'ITV au cours des séances. Il existe une forte corrélation entre les différents ITV 1, 2, 3 et global, ainsi qu'entre les volumes obtenus sur les différentes CBCT (p = 0,977). Le coefficient de corrélation entre les différents ITV et les volumes délinéés sur CBCT était élevé pour les lésions lobaires supérieures. En termes de tolérance, le VEMS (volume maximal expiré pendant la première seconde) ne semblait pas être un facteur significatif influant sur la corrélation entre les ITV et les volumes délinées sur CBCT. La réalisation d'une seule scanographie de centrage quadridimensionnelle est suffisante pour envisager une irradiation stéréotaxique pulmonaire, quelle que soit la localisation des lésions pulmonaires. Le coefficient de corrélation entre les ITV et les CBCT était élevé pour les lésions lobaires supérieures. Stereotactic lung radiosurgery has been carried out in the team at the Georges-François-Leclerc centre (CGFL) in Dijon since 2008 on a Truebeam® accelerator (Varian®) with the RPM technique. Fifty patients with primary T1–T2 stage lung cancer (n = 30) or lung metastasis (n = 20) were included in the study. Since 2014, 3 successive 4D scanners on D1, D2 and D3, have been produced in order to ensure the reproducibility of ITV (Internet Target Volume). The 3 ITVs are contoured (ITV 1, 2 and 3) from the MIP (Maximum Intensity Projection) of each of the 3 scanners. A global ITV is created from the ITV volumes of the 3 scanners (MIP 2 and 3 merged with MIP 1). A CBCT (Cone Beam Computerised Tomography) is performed at the start of each irradiation session to position the patient. The study consisted in analysing the relevance of the realisation of 3 different scanners before dosimetry to define the ITV and in comparing the volumes contoured on the different CBCT to the ITV to make sure that the tumour volume is well included in the ITV during the sessions. There is a strong correlation between the different ITVs 1, 2, 3 and global, as well as between the volumes obtained on the different CBCTs. The correlation coefficient between the different ITVs and the volumes contoured on CBCT was high for upper lobar lesions. In terms of tolerance, the FEV1 (Maximum volume expired during the first second) did not seem to be a significant factor influencing the correlation between the ITV and the volumes bypassed on CBCT. Performing a single 4D planification CT is sufficient to consider stereotactic lung irradiation, regardless of the location of the lung lesions. The correlation coefficient between ITV and CBCT was high for upper lobar lesions. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to build radiogenomics models from texture signatures derived from computed tomography (CT) and 18F-FDG PET-CT (FDG PET-CT) images of non-small cell lung cancer (NSCLC) with and without epidermal growth factor receptor (EGFR) mutations. Methods: Fifty patients diagnosed with NSCLC between 2011 and 2015 and with known EGFR mutation status were retrospectively identified. Texture features extracted from pretreatment CT and FDG PET-CT images by manual contouring of the primary tumor were used to develop multivariate logistic regression (LR) models to predict EGFR mutations in exon 19 and exon 20. Results: An LR model evaluating FDG PET-texture features was able to differentiate EGFR mutant from wild type with an area under the curve (AUC), sensitivity, specificity, and accuracy of 0.87, 0.76, 0.66, and 0.71, respectively. The model derived from CT texture features had an AUC, sensitivity, specificity, and accuracy of 0.83, 0.84, 0.73, and 0.78, respectively. FDG PET-texture features that could discriminate between mutations in EGFR exon 19 and 21 demonstrated AUC, sensitivity, specificity, and accuracy of 0.86, 0.84, 0.73, and 0.78, respectively. Based on CT texture features, the AUC, sensitivity, specificity, and accuracy were 0.75, 0.81, 0.69, and 0.75, respectively. Conclusion: Non-small cell lung cancer texture analysis using FGD-PET and CT images can identify tumors with mutations in EGFR. Imaging signatures could be valuable for pretreatment assessment and prognosis in precision therapy. [ABSTRACT FROM AUTHOR]

Background: Non‐small cell lung cancer (NSCLC) is one of the most malignant cancers worldwide and its pathogenesis is not completely clear. In this study, we explored the functions and mechanisms of exosomes transferring miR‐3180‐3p in NSCLC progression. Methods: The expression levels of miR‐3180‐3p in NSCLC tissues and paracarcinoma tissues was obtained from the GEO database (GEO: GSE53882). Exosomes derived from A549 cells were identified. Proliferation, migration and invasion were measured after treatment with exosomal miR‐3180‐3p or transfection using miR‐3180‐3p mimics. The relationship between miR‐3180‐3p and forkhead box P4 (FOXP4) was predicted using a bioinformatic tool and measured using a dual‐luciferase reporter gene assay and western blotting. Finally, a mouse xenograft model of NSCLC cells was established to verify the function of exosomal miR‐3180‐3p in vivo. Results: We found that miR‐3180‐3p decreased in both NSCLC cell lines and patient tissues. Overexpression of miR‐3180‐3p or treatment with exosomal miR‐3180‐3p significantly suppressed cell proliferation and metastasis in NSCLC cell lines. Subsequently, we found miR‐3180‐3p downregulated FOXP4 protein expression levels. Furthermore, the volumes and weights of nude mouse tumors expressing exosomal miR‐3180‐3p were significantly reduced. Conclusions: Exosomal miR‐3180‐3p suppresses NSCLC progression by downregulating FOXP4 expression. Key points: Significant findings of the study: We found that exosomal miR‐3180‐3p suppressed NSCLC progression and also identified a miR‐3180‐3p target gene. These findings provide a foundation to determine innovative therapeutic strategies. What this study adds: This study contributes to research investigating exosomal containing miRNAs. [ABSTRACT FROM AUTHOR]

Background: Non‐small cell lung cancer (NSCLC) accounts for 85% of lung cancer which is the most frequently diagnosed malignancy in China. Colon cancer associated transcript 1 (CCAT1) acts as an oncogene in enhancing tumor progression. However, the effects of CCAT1 in NSCLC remain unclear. The purpose of this study was to explore the role of CCAT1 in NSCLC. Methods: Wound healing and transwell assays were performed to measure cell migration. RT‐qPCR was employed to calculate the mRNA level of CCAT1 and miR‐490. Results: High expression of CCAT1 was observed in NSCLC tissues and cells, with low expression of miR‐490. CCAT1 promoted the proliferation and metastasis of H1299 and A549 cells, while miR‐490 had the opposite effect. CCAT1 could specifically bind to miR‐490 and regulate its expression. MiR‐490 partially reversed the inhibitory effect of CCAT1 on cell proliferation and metastasis. Conclusions: The CCAT1/miR‐490 molecular axis has been shown to be important for the treatment of NSCLC. [ABSTRACT FROM AUTHOR]

Non‐small cell lung cancer (NSCLC) accounts for approximately one in five cancer‐related deaths, and management requires increasingly complex decision making by health care professionals. Many centers have therefore adopted a multidisciplinary approach to patient care, using the expertise of various specialists to provide the best evidence‐based, personalized treatment. However, increasingly complex disease staging, as well as expanded biomarker testing and multimodality management algorithms with novel therapeutics, have driven the need for multifaceted, collaborative decision making to optimally guide the overall treatment process. To keep up with the rapidly evolving treatment landscape, national‐level guidelines have been introduced to standardize patient pathways and ensure prompt diagnosis and treatment. Such strategies depend on efficient and effective communication between relevant multidisciplinary team members and have both improved adherence to treatment guidelines and extended patient survival. This article highlights the value of a multidisciplinary approach to diagnosis and staging, treatment decision making, and adverse event management in NSCLC. Implications for Practice: This review highlights the value of a multidisciplinary approach to the diagnosis and staging of non‐small cell lung cancer (NSCLC) and makes practical suggestions as to how multidisciplinary teams (MDTs) can be best deployed at individual stages of the disease to improve patient outcomes and effectively manage common adverse events. The authors discuss how a collaborative approach, appropriately leveraging the diverse expertise of NSCLC MDT members (including specialist radiation and medical oncologists, chest physicians, pathologists, pulmonologists, surgeons, and nursing staff) can continue to ensure optimal per‐patient decision making as treatment options become ever more specialized in the era of biomarker‐driven therapeutic strategies. This article highlights the value of a multidisciplinary approach to diagnosis and staging, treatment decision making, and adverse event management in non‐small cell lung cancer. [ABSTRACT FROM AUTHOR]

Background: Real-world data are lacking on patients with small-cell lung cancer (SCLC) with extensive-stage SCLC (eSCLC) and poor performance status (PS). Patients & methods: Eligible patients diagnosed with eSCLC between 1 January 2008 and 31 December 2017 were included in this retrospective, observational study. Results: The study included 406 patients, with 14.3% impaired PS. Progression-free survival and overall survival were not significantly different between impaired (Eastern Cooperative Oncology Group ≥2) and not impaired patients (median, 4.5 vs 5.3 months, and 7.2 vs 8.4 months, respectively). Impaired patients used more supportive care drugs (mean, 3.0 vs 2.0; p = 0.033). Conclusion: Effectiveness outcomes among patients with and without impaired PS did not differ in the real-world setting. Progression-free survival and overall survival were similar to data from clinical trials. [ABSTRACT FROM AUTHOR]

Gefitinib is a selective tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) used for the treatment of malignant neoplasms. The most frequent skin complication during gefitinib therapy is an acneiform papulopustular eruption, usually distributed in the seborrheic areas but occasionally widespread. We report a patient with erosive pustular dermatosis of the scalp, a neutrophilmediated skin disease presenting with sterile pustules evolving into erosions and crusts on the scalp, during treatment with the EGFR inhibitor gefitinib for lung cancer. A literature review of the drug-induced cases of this rare entity is provided. [ABSTRACT FROM AUTHOR]

PURPOSE Omic-informed therapy is being used more frequently for patients with non-small-cell lung cancer (NSCLC) being treated on the basis of evidence-based decision-making. However, there is a lack of a standardized framework to evaluate those decisions and understand the association between omics-based management strategies and survival among patients. Therefore, we compared outcomes between patients with lung adenocarcinoma who received omics-driven targeted therapy versus patients who received standard therapeutic options. PATIENTS AND METHODS This was a retrospective study of patients with advanced NSCLC adenocarcinoma (N = 798) at City of Hope who received genomic sequencing at the behest of their treating oncologists. A thoracic oncology registry was used as a clinicogenomic database to track patient outcomes. RESULTS Of 798 individuals with advanced NSCLC (median age, 65 years [range, 22-99 years]; 60% white; 50% with a history of smoking), 662 patients (83%) had molecular testing and 439 (55%) received targeted therapy on the basis of the omic-data. A fast-and-frugal decision tree (FFT) model was developed to evaluate the impact of omics-based strategy on decision-making, progression-free survival (PFS), and overall survival (OS). We calculated that the overall positive predictive value of the entire FFT strategy for predicting decisions regarding the use of tyrosine kinase inhibitor-based targeted therapy was 88% and the negative predictive value was 96%. In an adjusted Cox regression analysis, there was a significant correlation with survival benefit with the FFT omics-driven therapeutic strategy for both PFS (hazard ratio [HR], 0.56; 95% CI, 0.42 to 0.74; P < .001) and OS (HR, 0.51; 95% CI, 0.36 to 0.71; P < .001) as compared with standard therapeutic options. CONCLUSION Among patients with advanced NSCLC who received care in the academic oncology setting, omics-driven therapy decisions directly informed treatment in patients and was correlated with better OS and PFS. [ABSTRACT FROM AUTHOR]

The genetic and metabolic heterogeneity of RAS-driven cancers has confounded therapeutic strategies in the clinic. To address this, rapid and genetically tractable animal models are needed that recapitulate the heterogeneity of RAS-driven cancers in vivo. Here, we generate a Drosophila melanogaster model of Ras/Lkb1 mutant carcinoma. We show that low-level expression of oncogenic Ras (RasLow) promotes the survival of Lkb1 mutant tissue, but results in autonomous cell cycle arrest and non-autonomous overgrowth of wild-type tissue. In contrast, high-level expression of oncogenic Ras (RasHigh) transforms Lkb1 mutant tissue resulting in lethal malignant tumors. Using simultaneous multiview light-sheet microcopy, we have characterized invasion phenotypes of Ras/Lkb1 tumors in living larvae. Our molecular analysis reveals sustained activation of the AMPK pathway in malignant Ras/Lkb1 tumors, and demonstrate the genetic and pharmacologic dependence of these tumors on CaMK-activated Ampk. We further show that LKB1 mutant human lung adenocarcinoma patients with high levels of oncogenic KRAS exhibit worse overall survival and increased AMPK activation. Our results suggest that high levels of oncogenic KRAS is a driving event in the malignant transformation of LKB1 mutant tissue, and uncovers a vulnerability that may be used to target this aggressive genetic subset of RAS-driven tumors. Rackley, Seong et al use a Drosophila model of Ras/Lkb1 mutant carcinoma to show that high levels of the KRAS oncogene drive the malignant transformation of LKB1 mutant tissue. This pathway could be used as a target for future therapies that aim to treat RAS-driven tumours. [ABSTRACT FROM AUTHOR]

Background: Durvalumab after concurrent chemoradiotherapy (CCRT) for locally advanced non‐small cell lung cancer (LA‐NSCLC) has been found to significantly improve overall survival (OS). However, the effect of durvalumab on local control remains unclear. Here, we evaluated the effect of the durvalumab on local control in comparison with the clinical result of patients treated with CCRT alone. Methods: A total of 120 LA‐NSCLC patients including 76 patients with CCRT alone and 44 patients with CCRT followed by durvalumab were analyzed. Baseline patient characteristics of CCRT alone cohort and durvalumab cohort were compared with student's t test or Mann–Whitney U test for continuous variables and with chi‐squared test for categorical variables. Local control (LC), progression free survival (PFS) and OS rates were estimated using the Kaplan–Meier method and compared with the log‐rank test. Results: There were 19 patients with stage II disease and 101 patients with stage III disease. Age, sex, histopathological type, T classification, N classification, clinical stage, tumor volume and dose fractionation schedule were not significantly different between the CCRT alone and durvalumab cohorts. The one‐year LC rate was significantly higher in the durvalumab cohort (86%) compared with the CCRT alone cohort (62%) (P = 0.005), whereas no significant difference was observed in either PFS (P = 0.864) or OS (P = 0.443) between the CCRT and durvalumab cohorts. Conclusions: The one‐year LC rate was significantly higher in the durvalumab cohort compared with the CCRT alone cohort. Although the follow‐up period was too short to draw definitive conclusions, the study revealed that durvalumab might have a significant effect on LC. Key points: Significant findings of the study: Effect of durvalumab on local control after chemoradiotherapy for locally advanced non‐small cell lung cancer is unclear What this study adds: The one‐year local control rate of chemoradiotherapy followed by durvalumab was significantly higher compared with chemoradiotherapy alone. [ABSTRACT FROM AUTHOR]

Lung cancer is the most commonly occurring cancer in men and the third most commonly occurring cancer in women. Contrary to other cancers, lung cancer often occurs in patients with comorbidities that can prevent the realisation of some treatments. The recommended treatment for patients presenting with stage I non-small cell lung cancer (NSCLC) is an anatomical surgical resection-lobectomy- and a systematic lymph node dissection. Many patients are, however, unfit to undergo surgery and consequently they often do not receive any curative therapy. This involves the elderly patients or patients with many co-morbidities. When an elderly patient with co-morbidities comes to the thoracic surgeon with early-stage lung cancer, if he is healthy and in good general condition he is taken to the operating room and undergoes lobectomy and lymph node dissection. If he is vulnerable and appropriate treatment is considered high risk he is treated with alternative therapies. SBRT is important alternative therapy. Stereotactic body radiation therapy (SBRT), interchangeably known as stereotactic ablative radiotherapy (SABR) is a modality that delivers ablative doses of radiation to extra-cranial targets with a degree of precision and accuracy above what can be reasonably achieved with conventionally fractionated external beam radiotherapy. Additionally, SBRT as a noninvasive therapy offers an attractive option for patients who are opposed to a surgical option. But questions have arisen regarding the suitability of SBRT for medically operable patients. Data from new trials are needed more than ever to inform and guide our multidisciplinary decisions for patients with earlystage NSCLC who are fit enough to undergo lung cancer surgery but may instead be more interestedin SBRT. In any case, good cooperation between surgeons and radiotherapists is of particular importance for the better treatment of these vulnerable patients. [ABSTRACT FROM AUTHOR]

Copyright of NaUKMA Research Papers. Biology & Ecology is the property of National University of Kyiv-Mohyla Academy, Faculty of Humanities and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Over the past decade, significant advances have been achieved in the diagnostic testing, treatment, and prognosis of advanced non--small-cell lung cancer (NSCLC). One of the most significant developments was the identification of specific gene alterations that define subsets of NSCLC. In 2007, ROS1 rearrangements were first described and observed in approximately 1%-2% of patients with NSCLC. Currently, crizotinib remains the therapy of choice for advanced ROS1-rearranged NSCLC without CNS metastases, while entrectinib has emerged as the preferred option for those with CNS metastases. The next-generation inhibitors under development are more potent, have better CNS efficacy, and can overcome important resistance mutations. In this review, we focus on the management of patients with advanced NSCLC harboring a ROS1 rearrangement. We aim to provide insight into the diagnosis, treatment approach, and emerging treatments in this subgroup of NSCLC. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors such as afatinib are used for nonsmall cell lung cancer (NSCLC) and show varying efficacy depending on EGFR gene mutation. Few studies have examined the relationship between EGFR gene mutations and the adverse events of afatinib in NSCLC. This retrospective study included 32 Japanese patients with NSCLC with EGFR gene mutation who were treated with afatinib between May 2014 and August 2018 at Kagawa University Hospital. Among the 32 Japanese patients with NSCLC treated with afatinib, 19 patients were positive for exon 19 deletion mutation (Del 19) and 13 patients were negative for Del 19. The incidence of grade = 2 skin rash was slightly higher in patients positive for Del 19 (42.1% vs. 7.7%, P = 0.050). No significant differences were detected in other adverse events between the two patient groups. Patients positive for Del 19 also showed significantly longer median progression-free survival (288 vs. 84 days, P = 0.049). Our study indicates a higher incidence of skin rash associated with afatinib treatment in Japanese patients with NSCLC positive for Del 19 compared with patients without Del 19. The Del 19 positive patient group also showed better progression-free survival. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) represents the most common histological type of lung cancer, characterized by a five-year survival rate of 15% and poor prognosis. Accumulating evidence indicates a prominent role of endoplasmic reticulum (ER) stress and the protein kinase RNA-like ER kinase (PERK)-dependent pathway of the unfolded protein response (UPR) in the pathogenesis of NSCLC. Increased expression of downstream targets of PERK was observed in various subtypes of NSCLC, and it was associated with a more aggressive phenotype, high risk of recurrence, and poor prognosis. Therefore, the present study aimed to investigate the biological effect of the selective PERK inhibitor NCI 159456 on A549 NSCLC cells and Human Pulmonary Fibroblasts (HPF) in vitro. Treatment of both normal and ER-stressed A549 cells with NCI 159456 resulted in a significant increase in the mRNA expression level of pro-apoptotic genes like activating transcription factor 4 ( ATF4) , DNA damage inducible transcript 3 ( DDIT3) , and BCL2 Associated X, Apoptosis Regulator ( BAX) as well as a decreased level of the anti-apoptotic gene B-cell lymphoma 2 (Bcl-2) . Cytotoxicity and genotoxicity analyses revealed that NCI 159456 significantly decreased viability and increased DNA damage in A549 cells under normal and ER stress conditions. Caspase-3 and reactive oxygen species (ROS) detection assays demonstrated that NCI 159456 significantly induced apoptosis and increased the ROS level in normal and ER-stressed A549 cells. Importantly, treatment with the inhibitor did not affect substantially normal HPF cells at any used concentration. The results indicate that PERK inhibitors could potentially be applied as a targeted therapy for NSCLC., Competing Interests: The authors declare no conflicts of interest.

Objective. As a first-line treatment for non-small cell lung cancer (NSCLC), the efficacy of chemotherapy is still unsatisfactory. Moxibustion has been shown to improve the side effects of radiotherapy and chemotherapy and regulate immune function. This study aimed to explore the antitumor effects and potential mechanisms of combinatorial cisplatin and moxibustion treatment for NSCLC by targeting the tumor microenvironment. Methods. Lewis lung cancer (LLC)-bearing mice were induced and treated with cisplatin or/and moxibustion at ST36 (Zusanli), and the growth, weight, and area of the tumor were evaluated. The numbers of various T cell subsets and myeloid cells in the tumor were assessed by flow cytometry, and the gene expression of related markers and cytokines was detected with real-time quantitative polymerase chain reaction (RT-qPCR). In addition, the tumor vascular structure was investigated using CD31 and α-smooth muscle actin (α-SMA) immunofluorescence staining. The expression of the vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) was detected by immunohistochemical staining. Results. Both cisplatin and moxibustion inhibited LLC tumor growth and reduced both the tumor area and weight, with the combinatorial therapy showing superior outcomes. Moxibustion upregulated the infiltration of CD4+ T cells and Th1 cells in the tumor, and the combinatorial therapy increased the proportion of CD8+ cytotoxic T cells (CTLs), CD4+T cells, Th1, Th9 cells, and M1 macrophages, as well as the expression of Cd69, Ifng, and Cd86 mRNA. The combinatorial therapy improved vascular normalization by increasing both the microvessel density (MVD) and pericyte coverage (α-SMA area density) and inhibiting the expression of the VEGF. Conclusions. Combinatorial cisplatin and moxibustion treatment inhibited the LLC tumor growth by mechanisms related to the improvement of the tumor immune microenvironment and vascular normalization, providing an effective combinatorial therapy beneficial for patients with NSCLC. [ABSTRACT FROM AUTHOR]

For stage III non-small cell lung cancer (NSCLC), approximately a third of patients survive up to 5 years, with decreasing 5-year survival rates for stage IIIB and stage IIIC disease. Although curable, stage III NSCLC encompasses a diverse range of disease presentation, with an equally complex range of multi-modal treatment options, including systemic and local therapies for distant and local disease control, respectively. This complexity results in a number of challenges for the multi-disciplinary team (MDT) in achieving optimal treatment outcomes for patients. As multi-modality treatment is the preferred treatment strategy for all stage III disease, the focus of this article is the key surgical, chemotherapy and radiotherapy clinical trials as well as guidelines that currently outline radical therapy options for patients with both potentially resectable and unresectable stage III NSCLC. [ABSTRACT FROM AUTHOR]

Background: Accurate diagnosis and staging are crucial to ensure uniform allocation to the optimal treatment methods for non-small cell lung cancer (NSCLC) patients, but may differ among multidisciplinary tumor boards (MDTs). Discordance between clinical and pathologic TNM stage is particularly important for patients with locally advanced NSCLC (stage IIIA) because it may influence their chance of allocation to curative-intent treatment. We therefore aimed to study agreement on staging and treatment to gain insight into MDT decision-making.Research Question: What is the level of agreement on clinical staging and treatment recommendations among MDTs in stage IIIA NSCLC patients?Study Design and Methods: Eleven MDTs each evaluated the same 10 pathologic stage IIIA NSCLC patients in their weekly meeting (n = 110). Patients were selected purposively for their challenging nature. All MDTs received exactly the same clinical information and images per patient. We tested agreement in cT stage, cN stage, cM stage (TNM 8th edition), and treatment proposal among MDTs using Randolph's free-marginal multirater kappa.Results: Considerable variation among the MDTs was seen in T staging (κ, 0.55 [95% CI, 0.34-0.75]), N staging (κ, 0.59 [95% CI, 0.35-0.83]), overall TNM staging (κ, 0.53 [95% CI, 0.35-0.72]), and treatment recommendations (κ, 0.44 [95% CI, 0.32-0.56]). Most variation in T stage was seen in patients with suspicion of invasion of surrounding structures, which influenced such treatment recommendations as induction therapy and type. For N stage, distinction between N1 and N2 disease was an important source of discordance among MDTs. Variation occurred between 2 patients even regarding M stage. A wide range of additional diagnostics was proposed by the MDTs.Interpretation: This study demonstrated high variation in staging and treatment of patients with stage IIIA NSCLC among MDTs in different hospitals. Although some variation may be unavoidable in these challenging patients, we should strive for more uniformity. [ABSTRACT FROM AUTHOR]

Background: Invasive mucinous adenocarcinoma (IMA) of the lung is a rare and distinct subtype of adenocarcinoma that can appear as airspace opacities on computed tomography (CT). In daily practice, we have occasionally encountered spontaneous regression of airspace opacities (SRAs) without treatment on serial CTs in patients with IMAs, which has not previously been described in the literature. Here, we describe serial CT findings with emphasis on SRAs in relation to clinicopathological features and treatment outcomes in patients with IMAs. Methods: A total of 46 patients with pathologically‐confirmed IMAs of the lung from January 2013 to June 2018 were included. Serial CT scans were reviewed and the patients were classified into SRA and no‐SRA groups according to the presence of SRA. Radiological features, clinicopathological characteristics, and treatment outcomes were compared between the SRA and no‐SRA groups. Results: A total of 32 patients were included in the no‐SRA group and 14 patients in the SRA group. IMAs in the SRA group were mostly pneumonic (P < 0.001), larger (P < 0.001), multifocal (P = 0.001), and showed higher stage (P < 0.001) on initial CT. Of seven patients who died during follow‐up, six were from the SRA group (P < 0.001). Mean overall survival for all IMAs was 86.6 months (range, 0–110 months), and the SRA group showed significantly worse overall survival (P < 0.001). Conclusions: IMAs of the lung showing SRAs on serial CTs are larger and multifocal, and tend to be pneumonic in type on initial CT. Patients present at a higher stage of disease, with higher mortality rate and reduced overall survival. Key points: Significant findings of the study: Invasive mucinous adenocarcinomas (IMAs) of the lung can show spontaneous regression of airspace opacities (SRAs) on serial CTs, without being correlated to the administration of anticancer drugs. IMAs that showed SRAs demonstrated reduced overall survival in patients. What this study adds: When airspace opacities show regression on CT, IMA should still be included in the differential diagnosis. A more careful application of RECIST 1.1 is needed in the assessment of tumor response of IMAs. [ABSTRACT FROM AUTHOR]

Background/purpose: There is a lack of data on nivolumab treatment outcomes in Taiwanese patients with advanced or recurrent non-small cell lung cancer (NSCLC) ineligible for radical radiotherapy and resistant to platinum-based chemotherapy. We investigated the safety and efficacy of nivolumab in this population.Methods: In this ongoing, multicenter, open-label, single-arm, phase II study, patients aged ≥20 years with a performance status of 0-1 and stage IIIB/IV or recurrent NSCLC received nivolumab 3 mg/kg every 2 weeks in 6-week cycles. Interim data obtained between 27 January 2016 and 21 May 2017 were analyzed. Safety, based on adverse event (AE) reporting, was the primary endpoint. Efficacy assessment parameters included overall response rate (ORR), overall survival (OS), and progression-free survival (PFS).Results: Among 53 treated patients with advanced NSCLC (median age 61.0 years; 62.3% male), mean treatment duration was 99.7 days. AEs (any grade) and serious AEs were reported by 92.5% and 47.2% of patients, respectively. Adverse drug reactions (ADRs; any) occurred in 58.5% of patients; grade ≥3 ADRs occurred in 13.2% of patients. Five deaths occurred; two cases (neoplasm progression and septic shock) were considered treatment-emergent. Common ADRs were fatigue (17.0%) and rash (13.2%). Common immune-related treatment-emergent AEs were rash (17.0%) and pruritus (13.2%). The centrally assessed ORR was 9.4% (5/53). The median OS and median PFS were 11.5 months and 1.4 months, respectively.Conclusion: Nivolumab appeared to be safe and effective in Taiwanese patients. These interim results suggest that nivolumab is a suitable treatment option for this population.Clinical Trial Registration: NCT02582125. [ABSTRACT FROM AUTHOR]

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Introduction: Lung cancer has a high mortality rate mainly due to the lack of early detection or outward signs and symptoms, thereby often progressing to advanced stages (e.g., stage IV) before it is diagnosed. However, if lung cancers can be diagnosed at an early stage and also if clinicians can prospectively identify patients likely to respond to specific treatments, then there is a very high potential to increase patients' survival. In recent years, several investigations have been conducted to identify cancer biomarkers for lung cancer risk assessment, early detection and diagnosis, the likelihood of identifying the group of patients who will benefit from a particular treatment and monitoring patient response to treatment. Materials and Methods: This paper reports on the review of 19 current clinical and emerging biomarkers used in risk assessment, screening for early detection and diagnosis and monitoring the response of treatment of non-small-cell lung cancers. Conclusion: The future holds promise for personalised and targeted medicine from prevention, diagnosis to treatment, which take into account individual patient's variability, though it depends on the development of effective biomarkers interrogating the key aberrant pathways and potentially targetable with molecular targeted or immunologic therapies. Lung cancer biomarkers have the potential to guide clinical decision-making since they can potentially detect the disease early, measure the risk of developing the disease and the risk of progression, provide accurate information of patient response to a specific treatment and are capable of informing clinicians about the likely outcome of a cancer diagnosis independent of the treatment received. Moreover, lung cancer biomarkers are increasingly linked to specific molecular pathway deregulations and/or cancer pathogenesis and can be used to justify the application of certain therapeutic or interventional strategies. [ABSTRACT FROM AUTHOR]

Background: The aim of this project was to collect real-world evidence and describe treatment patterns for stage III non-small cell lung cancer in Central and Eastern Europe. Based on real-world evidence, an expert opinion was developed, and the unmet needs and quality indicators were identified. Patients and methods: A systematic literature search and a multidisciplinary expert panel of 10 physicians from 7 countries used a modified Delphi process to identify quality indicators and unmet needs in patients with stage III non-small cell lung cancer. The profound questionnaire was used to characterize treatment patterns used for stage III non-small cell lung cancer, and a systematic review identified patterns in Central and Eastern Europe. The first questionnaire was completed by a group of medical oncologists, radiation oncologists and pneumologists. The panel of experts attended an in-person meeting to review the results of the questionnaire and to process a second round Delphi. An additional survey was then compiled and completed by the panel. Results: A complete consensus was reached by the panel of experts on a set of evidence-based clinical recommendations. The experience-based questionnaire generated a highly variable map of treatment patterns within the region. A list of unmet needs and barriers to quality care were developed with near-unanimous consent of the panel of experts. Conclusions: The current landscape of diagnostic and therapeutic approaches in Central and Eastern European countries is highly variable. We identified several significant barriers, mainly related to the availability of diagnostic and imaging methods and low rates of chemoradiotherapy with curative intention as initial treatment for unresectable stage III NSCLC. [ABSTRACT FROM AUTHOR]

Atezolizumab is a humanized anti-PD-L1 immune checkpoint antibody that is currently used in many kinds of advanced carcinoma including metastatic non-small cell lung cancer. The cutaneous side effect profile reported only 20% of the patients which had only mild maculopapular rash that required no treatment. There is no case report of anti-PD-L1 antibody-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) eruptions. To the best of our knowledge, there is no case report of atezolizumab-induced SJS or SJS/TEN induced by anti-PD-L1 immune checkpoint antibodies. We believe that our report will be useful to dermatologists who are consultants in the inpatient settings, as atezolizumab is an anti-neoplastic agent that has a potential to be used in multiple malignancies.

Epidermal growth factor receptor gene exon 20 insertion mutations are seen in ∼4–12% of patients with epidermal growth factor receptor-mutant non-small cell lung cancer. However, there is no targeted therapy approved for the treatment of non-small cell lung cancer patients with these rare epidermal growth factor receptor mutations. Previous studies revealed that epidermal growth factor receptor gene exon 20 insertion mutations are unique in their ability to activate epidermal growth factor receptor without the typical structural changes associated with the common epidermal growth factor receptor mutations, reducing the clinical efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors currently approved for non-small cell lung cancer. Therefore, there is an urgent need to identify active epidermal growth factor receptor-tyrosine kinase inhibitors and other effective treatment strategies for non-small cell lung cancer patients with epidermal growth factor receptor gene exon 20 insertion mutations. Mobocertinib is a novel irreversible epidermal growth factor receptor-tyrosine kinase inhibitor that selectively targets epidermal growth factor receptor gene exon 20 insertion mutations. Preclinical study revealed that mobocertinib inhibited the viability of epidermal growth factor receptor gene exon 20 insertion mutations-driven patient-derived xenografts and murine orthotopic tumors more potently than traditional epidermal growth factor receptor-tyrosine kinase inhibitors. In a study recently published in Cancer Discovery, Gonzalvez et al. assessed the safety, tolerability, and antitumor efficacy of mobocertinib in metastatic non-small cell lung cancer patients with epidermal growth factor receptor gene exon 20 insertion mutations. They found that non-small cell lung cancer patients with epidermal growth factor receptor gene exon 20 insertion mutations can benefit from mobocertinib treatment. Additionally, the treatment-related toxicity of mobocertinib was manageable. These findings lay the foundation for the application of mobocertinib in epidermal growth factor receptor gene exon 20 insertion-mutated non-small cell lung cancer. [ABSTRACT FROM AUTHOR]

Although physicians rely on clinical trial data to guide cancer treatment decisions, patient characteristics and outcomes often differ between real-world and clinical trial populations. We analyzed retrospective clinical data collected from a prior authorization (PA) tool linked with payer claims data to describe outcomes of first-line treatment for metastatic non-small cell lung cancer among 2,108 patients. Duration of therapy was shorter than observed in clinical trials. Healthcare costs and hospitalizations varied substantially by regimen. PA clinical data linked with administrative claims enable head-to-head comparisons of contemporary cancer treatments used in routine clinical practice, which are not available from clinical trials. [ABSTRACT FROM AUTHOR]

Blockade of the programmed cell death 1 immune inhibitory pathway has revolutionized the treatment of advanced non-small cell lung cancer and led to significant improvements in overall survival. In contrast, early-stage surgically resectable lung cancer has had few treatment advances in many years and continues to be associated with a high risk of relapse despite apparent curative resection. In this review, we discuss the many ongoing efforts to incorporate programmed cell death 1 pathway blockade into the treatment paradigm for surgically resectable lung cancer both as adjuvant and neoadjuvant therapy. We review the early-phase results from neoadjuvant clinical trials, the landscape of phase III trials that are ongoing, and look to the future of immune checkpoint blockade as a potential curative therapy for surgically resectable lung cancer. [ABSTRACT FROM AUTHOR]

Background: Although mindfulness‐based interventions have been widely examined in patients with nonmetastatic cancer, the feasibility and efficacy of these types of programs are largely unknown for those with advanced disease. We pilot‐tested a couple‐based meditation (CBM) relative to a supportive‐expressive (SE) and a usual care (UC) arm targeting psychospiritual distress in patients with metastatic lung cancer and their spousal caregivers. Patients and Methods: Seventy‐five patient‐caregiver dyads completed baseline self‐report measures and were then randomized to one of the three arms. Couples in the CBM and SE groups attended four 60‐minute sessions that were delivered via videoconference. All dyads were reassessed 1 and 3 months later. Results: A priori feasibility benchmarks were met. Although attendance was high in both groups, dyads in the CBM group indicated greater benefit of the sessions than those in the SE group (patients, CBM mean = 2.63, SE mean = 2.20, p =.003; spouses, CBM mean = 2.71, SE mean = 2.00, p =.005). Compared with the UC group, patients in the CBM group reported significantly lower depressive symptoms (p =.05; d = 0.53) and marginally reduced cancer‐related stress (p =.07; d = 0.68). Medium effect sizes in favor of the CBM compared with the SE group for depressive symptoms (d = 0.59) and cancer‐related stress (d = 0.54) were found. Spouses in the CBM group reported significantly lower depressive symptoms (p <.01; d = 0.74) compared with those in the UC group. Conclusion: It seems feasible and possibly efficacious to deliver dyadic interventions via videoconference to couples coping with metastatic lung cancer. Mindfulness‐based interventions may be of value to managing psychological symptoms in the palliative care setting. Clinical trial identification number. NCT02596490 Implications for Practice: The current randomized controlled trial has established that a mindfulness approach to the management of patients' and spouses' psychospiritual concerns is acceptable and subjectively deemed more beneficial than a supportive‐expressive treatment for patients with metastatic non‐small cell lung cancer (NSCLC). We also revealed that videoconference delivery, here FaceTime, is an acceptable approach even for geriatric patients with metastatic NSCLC and that patients and their spousal caregivers prefer a dyadic delivery of this type of supportive care strategy. Lastly, this trial has laid the foundation for the role of mindfulness‐based interventions in the palliative care setting supporting patients with advanced NSCLC and their spousal caregivers. The feasibility and efficacy of mindfulness‐based interventions for patients with advanced cancer have not been widely examined. This article describes a couple‐based Meditation intervention compared with a supportive expressive intervention and a usual care control group, targeting psychospiritual distress in patients with metastatic lung cancer and their spousal caregivers. [ABSTRACT FROM AUTHOR]