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Background and Objectives: Treatment of advanced lung cancer (LC) has become increasingly personalized over the past decade due to an improved understanding of tumor molecular biology and antitumor immunity. The main task of a pulmonologist oncologist is to establish a tumor diagnosis and, ideally, to confirm the stage of the disease with the least invasive technique possible. Materials and Methods: The paper will summarize published reviews and original papers, as well as published clinical studies and case reports, which studied the role and compared the methods of invasive pulmonology diagnostics to obtain adequate tumor tissue samples for molecular analysis, thereby determining the most effective molecular treatments. Results: Bronchoscopy is often recommended as the initial diagnostic procedure for LC. If the tumor is endoscopically visible, the biopsy sample is susceptible to molecular testing, the same as tumor tissue samples obtained from surgical resection and mediastinoscopy. The use of new sampling methods, such as cryobiopsy for peripheral tumor lesions or cytoblock obtained by ultrasound-guided transbronchial needle aspiration (TBNA), enables obtaining adequate small biopsies and cytological samples for molecular testing, which have until recently been considered unsuitable for this type of analysis. During LC patients' treatment, resistance occurs due to changes in the mutational tumor status or pathohistological tumor type. Therefore, the repeated taking of liquid biopsies for molecular analysis or rebiopsy of tumor tissue for new pathohistological and molecular profiling has recently been mandated. Conclusions: In thoracic oncology, preference should be given to the least invasive diagnostic procedure providing a sample for histology rather than for cytology. However, there is increasing evidence that, when properly processed, cytology samples can be sufficient for both the cancer diagnosis and molecular analyses. A good knowledge of diagnostic procedures is essential for LC diagnosing and treatment in the personalized therapy era. [ABSTRACT FROM AUTHOR]

Background and Objectives: Treatment of advanced lung cancer (LC) has become increasingly personalized over the past decade due to an improved understanding of tumor molecular biology and antitumor immunity. The main task of a pulmonologist oncologist is to establish a tumor diagnosis and, ideally, to confirm the stage of the disease with the least invasive technique possible. Materials and Methods: The paper will summarize published reviews and original papers, as well as published clinical studies and case reports, which studied the role and compared the methods of invasive pulmonology diagnostics to obtain adequate tumor tissue samples for molecular analysis, thereby determining the most effective molecular treatments. Results: Bronchoscopy is often recommended as the initial diagnostic procedure for LC. If the tumor is endoscopically visible, the biopsy sample is susceptible to molecular testing, the same as tumor tissue samples obtained from surgical resection and mediastinoscopy. The use of new sampling methods, such as cryobiopsy for peripheral tumor lesions or cytoblock obtained by ultrasound-guided transbronchial needle aspiration (TBNA), enables obtaining adequate small biopsies and cytological samples for molecular testing, which have until recently been considered unsuitable for this type of analysis. During LC patients’ treatment, resistance occurs due to changes in the mutational tumor status or pathohistological tumor type. Therefore, the repeated taking of liquid biopsies for molecular analysis or rebiopsy of tumor tissue for new pathohistological and molecular profiling has recently been mandated. Conclusions: In thoracic oncology, preference should be given to the least invasive diagnostic procedure providing a sample for histology rather than for cytology. However, there is increasing evidence that, when properly processed, cytology samples can be sufficient for both the cancer diagnosis and molecular analyses. A good knowledge of diagnostic procedures is essential for LC diagnosing and treatment in the personalized therapy era.

Objective: To evaluate the impact of sequential (first- to third-generation) epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment on top-corrected QT interval (top-QTc) in non-small cell lung cancer (NSCLC) patients. Methods: We retrospectively reviewed the medical records of NSCLC patients undergoing sequential EGFR-TKI treatment at Shanghai Chest Hospital between October 2016 and August 2021. The heart rate (HR), top-QT interval, and top-QTc of their ECGs were extracted from the institutional database and analyzed. Logistic regression was performed to identify predictors for top-QTc prolongation. Results: Overall, 228 patients were enrolled. Compared with baseline (median, 368 ms, same below), both first-generation (376 ms vs. 368 ms, p < 0.001) and sequential third-generation EGFR-TKIs (376 ms vs. 368 ms, p = 0.002) prolonged top-QT interval to a similar extent (p = 0.635). Top-QTc (438 ms vs. 423 ms, p < 0.001) and HR (81 bpm vs.79 bpm, p = 0.008) increased after first-generation EGFR-TKI treatment. Further top-QTc prolongation (453 ms vs. 438 ms, p < 0.001) and HR increase (88 bpm vs. 81 bpm, p < 0.001) occurred after treatment advanced. Notably, as HR elevated during treatment, top-QT interval paradoxically increased rather than decreased, and the top-QTc increased rather than slightly fluctuated. Moreover, such phenomena were more significant after treatment advanced. After adjusting for confounding factors, pericardial effusion and lower serum potassium levels were independent predictors of additional QTc prolongation during sequential third-generation EGFR-TKI treatment. Conclusion: First-generation EGFR-TKI could prolong top-QTc, and sequential third-generation EGFR-TKI induced further prolongation. Top-QT interval paradoxically increased and top-QTc significantly increased as HR elevated, which was more significant after sequential EGFR-TKI treatment. Pericardial effusion and lower serum potassium levels were independent predictors of additional QTc prolongation after sequential EGFR-TKI treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: The following paper was developed as a reference for healthcare workers who are looking for information on advanced non-small cell lung cancers that lack driver mutations and their treatment with immunotherapy. The aim of the present study is to provide a reliable data source based on a review of the most current papers on the PD-1/PD-L1 and CTLA-4 inhibitors, as well as their use in medical practice. From a complete literature review, we were able to present in this paper what is most current in the treatment with immunotherapy for advanced non-small cell lung cancer (NSCLC). Especially the use of immunotherapy, particularly inhibitors of PD-1 (programmed cell death protein 1), PDL-1 (programmed cell death protein ligand 1), and CTLA-4 (cytotoxic T-lymphocyte antigen 4). Since 2015, these drugs have transformed the treatment of advanced NSCLC lacking driver mutations, evolving from second-line therapy to first-line, with excellent results. The arrival of new checkpoint inhibitors such as cemiplimab and the use of checkpoint inhibitors earlier in the therapy of advanced and metastatic cancers has been making the future prospects for treating NSCLC lacking driver mutations more favorable and optimistic. In addition, for those patients who have low PDL-1 positivity tumors, the combination of cytotoxic chemotherapy, VEGF inhibitor, and immunotherapy have shown an important improvement in global survival and progression free survival regardless the PDL-1 status. We also explored the effectiveness of adding radiotherapy to immunotherapy and the most current results about this combination. One concern that cannot be overlooked is the safety profile of immune checkpoint inhibitors (ICI) and the most common toxicities are described throughout this paper as well as tumor resistance to ICI. [ABSTRACT FROM AUTHOR]

Purpose: Timely access to supportive and palliative care (PC) remains a challenge. A proposed solution is to trigger an automatic referral process to PC by pre-determined clinical criteria. This study sought to co-design with patients and providers an automatic PC referral process for patients newly diagnosed with stage IV lung cancer. Methods: In Step 1 of this work, nine one on one phone interviews were conducted with advanced lung cancer patients on their perspectives on the acceptability of phone contact by a specialist PC provider triggered by an automatic referral process. Interviews were thematically analysed. Step 2: Patient advisors, healthcare providers (oncologists, nurses from oncology and PC, clinical social worker, psychologist), and researchers were invited to join a working group to provide input on the development and implementation of the automatic referral process. The group met biweekly (virtually) over the course of six months. Results: From interviews, the concept of an automatic referral process was perceived to be acceptable and beneficial for patients. Participants emphasized the need for timely support, access to peer and community resources. Using these findings, the co-design working group identified eligibility criteria for identifying newly diagnosed stage IV lung cancer patients using the cancer centre electronic health record, co-developed a telephone script for specialist PC providers, handouts on supportive care, and interview and survey guides for evaluating the implemented automatic process. Conclusion: A co-design process ensures stakeholders are involved in program development and implementation from the very beginning, to make outputs relevant and acceptable for stage IV lung cancer patients. [ABSTRACT FROM AUTHOR]

From a complete literature review, we were able to present in this paper what is most current in the treatment with immunotherapy for advanced non-small cell lung cancer (NSCLC). Especially the use of immunotherapy, particularly inhibitors of PD-1 (programmed cell death protein 1), PDL-1 (programmed cell death protein ligand 1), and CTLA-4 (cytotoxic T-lymphocyte antigen 4). Since 2015, these drugs have transformed the treatment of advanced NSCLC lacking driver mutations, evolving from second-line therapy to first-line, with excellent results. The arrival of new checkpoint inhibitors such as cemiplimab and the use of checkpoint inhibitors earlier in the therapy of advanced and metastatic cancers has been making the future prospects for treating NSCLC lacking driver mutations more favorable and optimistic. In addition, for those patients who have low PDL-1 positivity tumors, the combination of cytotoxic chemotherapy, VEGF inhibitor, and immunotherapy have shown an important improvement in global survival and progression free survival regardless the PDL-1 status. We also explored the effectiveness of adding radiotherapy to immunotherapy and the most current results about this combination. One concern that cannot be overlooked is the safety profile of immune checkpoint inhibitors (ICI) and the most common toxicities are described throughout this paper as well as tumor resistance to ICI.

Background: Immune checkpoint inhibitors (ICIs) have shown unprecedented clinical benefit in cancer immunotherapy and are rapidly transforming the practice of advanced lung cancer. However, resistance routinely develops in patients treated with ICIs. We conducted this retrospective study to provide an overview on clinical characteristics of ICI resistance, optimal treatment beyond disease progression after prior exposure to immunotherapy, as well as potential prognostic factors of such resistance. Methods: 190 patients diagnosed with unresectable lung cancer who received at least one administration of an anti-programmed cell death 1 (PD-1)/antiprogrammed cell death-ligand 1(PD-L1) at any treatment line at Zhongshan Hospital Fudan University between Sep 2017 and December 2019 were enrolled in our study. Overall survival (OS) and progression-free survival (PFS) were analyzed. Levels of plasma cytokines were evaluated for the prognostic value of ICI resistance. Results: We found that EGFR/ALK/ROS1 mutation and receiving ICI treatment as second-line therapy were risk factors associated with ICI resistance. Patients with bone metastasis at baseline had a significantly shorter PFS1 time when receiving initial ICI treatment. Whether or not patients with oligo-progression received local treatment seemed to have no significant effect on PFS2 time. Systemic therapies including chemotherapy and anti-angiogenic therapy rather than continued immunotherapy beyond ICI resistance had significant effect on PFS2 time. TNF, IL-6 and IL-8 were significantly elevated when ICI resistance. Lower plasma TNF level and higher plasma IL-8 level seemed to be significantly associated with ICI resistance. A nomogram was established to prognosis the clinical outcome of patients treated with ICIs. Conclusion: Patients with EGFR/ALK/ROS1 mutation, or those receiving ICI treatment as second-line therapy had higher risk of ICI resistance. Patients with bone metastasis had poor prognosis during immunotherapy. For those patients with oligo-progression after ICI resistance, combination with local treatment did not lead to a significantly longer PFS2 time. Chemotherapy and anti-angiogenic therapy rather than continued immunotherapy beyond ICI resistance had significant effect on PFS2 time. Levels of plasma cytokines including TNF, IL-6 and IL-8 were associated with ICI resistance. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with advanced small-cell lung cancer (SCLC) have a considerable symptom burden and may require extensive care. A crucial element of treatment for these patients is the integration of specialized palliative care (SPC). Timely integration of SPC for patients with advanced non-small cell lung cancer (NSCLC) improved quality of life and prolonged survival in large prospective trials. This study provides retrospective data for patients with SCLC with, and without SPC. The results and conclusions indicate that patients with advanced SCLC should participate in a consultation with a SPC team in a timely manner to ensure a benefit of SPC for this patient group. Timely integration of specialized palliative care (SPC) has been shown to improve cancer patients' quality of life (QoL) and reduced the use of medical services. To evaluate the level of integration of SPC services for patients with advanced small-cell lung cancer (SCLC), we retrospectively analyzed medical records of patients from 2019 to 2021. Regarding the timing of referral to SPC services, we defined four cutoffs for early referral according to the current literature: (a) SPC provided ≤ 60 days after diagnosis; (b) SPC provided ≥ 60 days before death; (c) SPC provided ≥ 30 days before death; and (d) SPC provided ≥ 130 days before death. One hundred and forty-three patients (94.1%) were found to have locally advanced (stage III) or metastatic (stage IV) disease. Sixty-eight were not referred to SPC services (47.6%), whereas 75 patients received SPC (52.4%). We found a significantly higher number of referrals to SPC services for patients with higher ECOG (Eastern Cooperative Oncology Group) (i.e., ECOG ≥ 2) (p = 0.010) and patients with stage IV disease (p ≤ 0.001). The median overall survival (OS) for SCLC stage III/IV patients (n = 143) who did not receive SPC treatment was 17 months (95% CI 8.5–25.5), while those who did receive SPC treatment had a median OS of 8 months (95% CI 6.2–9.8) (p = 0.014). However, when we evaluated patients receiving SPC treatment in a timely manner before death as suggested by the different cutoffs indicated in the literature, they lived significantly longer when referred at a minimum of ≥60 or ≥130 days before death. Based on our findings, we suggest that patients with advanced SCLC should participate in a consultation with a SPC team in a timely manner to ensure a benefit of SPC for this patient group. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was set to investigate the prognostic role of plasmatic levels of heat shock protein 90 alpha (HSP90α) at diagnosis in advanced lung cancer patients treated with Programmed cell death protein 1 (PD-1)/Programmed cell death-Ligand protein 1 (PD-L1) inhibitors plus chemotherapy. Methods: A total of 137 advanced lung cancer patients treated with PD-1/PD-L1 inhibitors plus chemotherapy admitted to the Guangxi Medical University Cancer Hospital were enrolled in this study. Smooth curve fitting was conducted to address the nonlinearity of HSP90α and progression-free survival (PFS) and overall survival (OS). We calculated the inflection point using a recursive algorithm. Kaplan–Meier survival analysis and Cox proportional hazards regression model were used to assess the prognostic value of HSP90α for PFS and OS. Subgroup analysis was performed to evaluate the relationship between high HSP90α and disease progression and death risk. Results: The average age of patients was 58.6 ± 9.8 years, and 73.7% of them were men. We divided patients according to their plasmatic levels of HSP90α into low (HSP90α <52.7 ng/ml) group and high (HSP90α ≥52.7 ng/ml) group. Kaplan–Meier analysis showed a shorter PFS and OS for the high group with log-rank P < 0.05. Univariate and multivariate analyses indicated that high HSP90α was associated with an increased risk of disease progression and death after fully adjusting potential confounders with hazard ratio (HR) 1.8 (95% CI = 1.0–3.2) and HR 2.4 (95% CI = 1.1–5.1), respectively (P < 0.05). After stratification by subgroup analysis, the relationship between high HSP90α and the risk of disease progression and death was consistent across all patient subgroups. Conclusion: Plasmatic levels of HSP90α at diagnosis can be considered a potential independent prognostic marker of advanced lung cancer patients treated with PD-1/PD-L1 inhibitors plus chemotherapy. A further large-scale prospective validation study is needed to determine whether these results are widely applicable. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that the skeletal muscle index at the third lumbar vertebra (L3 SMI) had reasonable specificity and sensitivity in nutritional assessment and prognostic prediction in digestive system cancers, but its performance in lung cancer needs further investigation.Methods: A retrospective study was performed on 110 patients with advanced lung cancer. The L3 SMI, the Patient-Generated Subjective Global Assessment score (PG-SGA score), body mass index (BMI), and serological indicators were analyzed. According to PG-SGA scores, patients were divided into severe malnutrition (≥9 points), mild to moderate malnutrition (≥3 points and ≤ 8 points), and no malnutrition (≤2 points) groups. Pearson correlation and logistic regression analysis were adopted to find factors related to malnutrition, and a forest plot was drawn. The receiver operating characteristic (ROC) curve was performed to compare the diagnostic values of malnutrition among factors, which were expressed by the area under curve (AUC).Results: 1. The age of patients in the severe malnutrition group, the mild to moderate malnutrition group, and the no malnutrition group significantly differed, with mean ages of 63.46 ± 10.01 years, 60.42 ± 8.76 years, and 55.03 ± 10.40 years, respectively (OR = 1.062, 95%CI: 1.008 ~ 1.118, P = 0.024; OR = 1.100, 95%CI: 1.034 ~ 1.170, P = 0.002). Furthermore, the neutrophil to lymphocyte ratio (NLR) of the severe malnutrition group was significantly higher than that of the no malnutrition group, with statistical significance. The difference between the mild to moderate malnutrition group and the no malnutrition group were not statistically significant, with NLR of 4.07 ± 3.34 and 2.47 ± 0.92, respectively (OR = 1.657,95%CI: 1.036 ~ 2.649, P = 0.035). The L3 SMI of patients in the severe malnutrition and mild to moderate malnutrition groups were significantly lower than that of the patients in the no malnutrition group, with statistical significance. The L3 SMI of patients in the severe malnutrition group, mild to moderate malnutrition group, and no malnutrition group were 27.40 ± 4.25 cm2/m2, 38.19 ± 6.17 cm2/m2, and 47.96 ± 5.02 cm2/m2, respectively (OR = 0.600, 95%CI: 0.462 ~ 0.777, P < 0.001; OR = 0.431, 95%CI: 0.320 ~ 0.581, P < 0.001). 2. The Pearson correlation analysis showed that the PG-SGA score positively correlated with age (r = 0.296, P < 0.05) but negatively correlated with L3 SMI (r = - 0.857, P < 0.05). The L3 SMI was also negatively correlated with age (r = - 0.240, P < 0.05). 3. The multivariate analysis showed that the L3 SMI was an independent risk factor for malnutrition (OR = 0.446, 95%CI: 0.258 ~ 0.773, P = 0.004; OR = 0.289, 95%CI: 0.159 ~ 0.524, P < 0.001).Conclusion: 1. The differences in the L3 SMI was statistically significant among advanced lung cancer patients with different nutritional statuses. 2. In the nutritional assessment of patients with lung cancer, the L3 SMI was consistent with the PG-SGA. 3. The L3 SMI is an independent predictor of malnutrition in patients with advanced lung cancer. [ABSTRACT FROM AUTHOR]