The Effects of GCSF Primary Prophylaxis on Survival Outcomes and Toxicity in Patients with Advanced Non-Small Cell Lung Cancer on First-Line Chemoimmunotherapy: A Sub-Analysis of the Spinnaker Study.

GCSF prophylaxis is recommended in patients on chemotherapy with a >20% risk of febrile neutropenia and is to be considered if there is an intermediate risk of 10−20%. GCSF has been suggested as a possible adjunct to immunotherapy due to increased peripheral neutrophil recruitment and PD-L1 expression on neutrophils with GCSF use and greater tumour volume decrease with higher tumour GCSF expression. However, its potential to increase neutrophil counts and, thus, NLR values, could subsequently confer poorer prognoses on patients with advanced NSCLC. This analysis follows on from the retrospective multicentre observational cohort Spinnaker study on advanced NSCLC patients. The primary endpoints were OS and PFS. The secondary endpoints were the frequency and severity of AEs and irAEs. Patient information, including GCSF use and NLR values, was collected. A secondary comparison with matched follow-up duration was also undertaken. Three hundred and eight patients were included. Median OS was 13.4 months in patients given GCSF and 12.6 months in those not (p = 0.948). Median PFS was 7.3 months in patients given GCSF and 8.4 months in those not (p = 0.369). A total of 56% of patients receiving GCSF had Grade 1−2 AEs compared to 35% who did not receive GCSF (p = 0.004). Following an assessment with matched follow-up, 41% of patients given GCSF experienced Grade 1−2 irAEs compared to 23% of those not given GCSF (p = 0.023). GCSF prophylaxis use did not significantly affect overall or progression-free survival. Patients given GCSF prophylaxis were more likely to experience Grade 1−2 adverse effects and Grade 1−2 immunotherapy-related adverse effects.

Review of Lung Cancer Patient Characteristics and Treatment Strategies in the Pandemic Covid-19 Year.

Introduction: It is estimated that delays in diagnosis due to the COVID-19 pandemic in North Macedonia could result in significant reductions in the number of potentially curative stages in lung cancer patients. Purpose: The aim of this study was to review patient characteristics and treatment strategies of lung cancer patients treated at the University Clinic of Radiotherapy and Oncology (UCRO), during the pre-pandemic year (from 1 of March 2019 to the end of February 2020) and the pandemic year (from 1 of March 2020 to the end of February 2021). Material: We analyzed eligible patients in the course of these two years according to patient characteristics and treatment strategies. Results: We have a record increasing in number of undefined lung cancer patients without any pathological or histological conformation (11% pandemic year compared to 7% in the previous year), and an increased number of stage III and IV NSCLC patients in the pandemic year 449 (87%), in comparison to the pre-pandemic year of 403 (74%) patients. We have found a decreasing number of stage II NSCLC patients in the pandemic year 82 (13%) compared to 141 (26%) patients in the pre-pandemic year. We also note a decreasing number of patients with NSCLC operated on from 218 to 123 in the pandemic group. Due to frequent check-ups for COVID-19, we report an increasing number of early stage IA and stage IB patients, treated only by surgery. Conclusions: The strict screening and admittance criteria put in place by hospitals during the pandemic might have improved the oncology treatment course of lung cancer patients.

A study of the efficacy and toxicity outcomes of extended durvalumab dosing in patients with stage III unresectable non-small cell lung cancer (NSCLC) during the COVID-19 pandemic.

BACKGROUND: Durvalumab following chemoradiation in unresectable stage III non-small cell lung cancer (NSCLC) has led to improved outcomes. The schedule of administration has been determined by pharmacokinetic studies. This study evaluates real-world efficacy and safety outcomes of extended dosing (ED) vs. standard dosing (SD) of durvalumab. METHODS: Stage III NSCLC patients treated at the Cancer center of Southeastern Ontario with consolidative durvalumab from March 2017-December 2020 were included. Patient characteristics and outcomes were evaluated through retrospective review. Comparisons were made using chi-square and t-tests. Kaplan-Meier curves were used to analyze overall survival (OS). RESULTS: A total of 35 patients were included; 15 (43%) switched to ED. Distant recurrence rates were higher in the ED group (53% vs. 20%, p = 0.07), with no differences in the sites of disease recurrence. A similar proportion of patients were alive in the ED vs. SD group (93% vs. 80%, p = 0.3), with no significant difference in OS. There were less grade 3 or greater immune-related adverse events in the ED group (0% vs. 20%). Treatment discontinuation occurred in 47% vs. 50% in the ED vs. SD groups, respectively, owing to toxicity in 20% of patients in the ED group vs. 40% in the SD group. CONCLUSIONS: Extended dosing has similar efficacy and toxicity to standard dosing; however, there was a higher rate of toxicity necessitating discontinuation in the SD group, which may have impacted the clinical decision-making to switch to ED. Our data is limited by a small sample size and should be further validated in larger cohorts.

Hypermetabolic lymphadenopathy following the administration of COVID-19 vaccine and immunotherapy in a lung cancer patient: a case report.

BACKGROUND: Given the current climate of the pandemic, lung cancer patients are especially vulnerable to complications from severe acute respiratory syndrome coronavirus 2 infection. As a high-risk population group, these patients are strongly advised to receive coronavirus disease 2019 vaccination in accordance with Center for Disease Control and Prevention guidelines to minimize morbidity and mortality. In recent years, immunotherapy has taken a preeminent role in the treatment of non-small cell lung cancer with dramatic improvement in overall survival. Reactive lymphadenopathy following the administration of a coronavirus disease 2019 vaccination can confound the radiographic interpretation of positron emission tomography-computed tomography or computed tomography scans from lung cancer patients receiving immunotherapy. CASE PRESENTATION: Here, we present a case of a 61-year-old Caucasian female and former smoker who developed cervical, hilar, supraclavicular, mediastinal, and left retroauricular lymphadenopathy following her coronavirus disease 2019 booster vaccination. At the time, she had been receiving long-term immunotherapy for the treatment of advanced lung adenocarcinoma. Biopsy was pursued owing to concerns of treatment failure and confirmed recurrent malignancy. CONCLUSION: This case report highlights the importance of lymph node biopsies in lung cancer patients who present with contralateral lymphadenopathy following coronavirus disease 2019 vaccination to rule out tumor recurrence in this deserving patient population.

A case of cytokine release syndrome accompanied with COVID-19 infection during treatment with immune checkpoint inhibitors for non-small cell lung cancer.

Cytokine release syndrome (CRS) is a systemic inflammatory disease caused by a variety of factors, including infections and certain drugs. A 70-year-old man who was diagnosed with a postoperative recurrence of lung adenocarcinoma received nivolumab, ipilimumab, pemetrexed and carboplatin every 3 weeks for two cycles followed by nivolumab and ipilimumab, which resulted in a partial response. Four days after the dose of nivolumab, the patient returned with diarrhea and fever. The patient was diagnosed with COVID-19 infection accompanied by severe colitis. Although intensive care was performed, the patient suddenly went into cardiopulmonary arrest. Examination revealed an abnormally high interleukin-6 level, suggesting CRS. This is the first report of a patient with CRS accompanied with COVID-19 infection during treatment with ICIs. Cytokine release syndrome (CRS) is a systemic inflammatory disease caused by a variety of factors, including infections and certain drugs. Here, we report a case of non-small cell lung cancer with CRS caused by COVID-19 infection during treatment with nivolumab and ipilimumab. Fever is a common event in cancer patients, especially in COVID-19-infected patients, but when fever develops during cancer immunotherapy, CRS should always be kept in mind.

Optimising tissue acquisition and the molecular testing pathway for patients with non-small cell lung cancer: A UK expert consensus statement.

Targeted therapy against actionable variants has revolutionised the treatment landscape for non-small cell lung cancer (NSCLC). Approximately half of NSCLC adenocarcinomas have an actionable variant, making molecular testing a critical component of the diagnostic process to personalise therapeutic options, optimise clinical outcomes and minimise toxicity. Recently, genomic testing in England has undergone major changes with the introduction of Genomic Laboratory Hubs, designed to consolidate and enhance existing laboratory provision and deliver genomic testing as outlined in the National Genomic Test Directory. Similar changes are ongoing in Scotland, Wales and Northern Ireland. However, multiple challenges exist with current tissue acquisition procedures and the molecular testing pathway in the UK, including quantity and quality of available tissue, adequacy rates, test availability among genomic laboratories, turnaround times, multidisciplinary team communication, and limited guidance and standardisation. The COVID-19 pandemic has added an extra layer of complexity. Herein, we summarise best practice recommendations, based on expert opinion, to overcome existing challenges in the UK. The least invasive biopsy technique should be undertaken with the aim of acquiring the greatest quality and quantity of tissue. Use of sedation should be considered to improve patient experience. Rapid on-site evaluation may also be useful to help guide adequate sampling, and liquid biopsy may be beneficial in some instances. Sample processing should be appropriate to facilitate biomarker testing, in particular, next-generation sequencing for comprehensive genomic information. Steps to optimise tissue utilisation and turnaround times, such as planning of tissue usage, limiting immunohistochemistry, tumour enrichment, and reflex testing at diagnosis, should be implemented. Guidelines for tissue acquisition and sample processing may help to improve sample adequacy to perform downstream testing. Communication among genomic laboratories will help to standardise test availability across England and local auditing could identify further areas for optimisation, including ways to improve turnaround times and adequacy rates.

Overall survival and prognostic factors in Stage I lung adenocarcinoma treated with curative intent: A real-life 19-year cohort study.

OBJECTIVES: Important differences in Stage I non-small-cell lung cancer (NSCLC) are related to the delay in the diagnosis to the treatment, hospitals' specialised status, comorbidities, tumour stage and histological type. METHODS: A 19-year retrospective cohort study was conducted, including 681 patients with NSCLC in clinical-stage IA-IB. The variables analysed were gender, age, schooling, type of health care provider, type of treatment, period of 5-year treatment, the time between first attendance to diagnosis and the time between diagnosis and treatment, and hospital's specialised status. RESULTS: Patients who underwent radiotherapy alone had three times more risk of death than those who underwent surgery alone (adjusted hazard ratio [adjHR] = 3.44; 95% confidence interval [CI]: 2.45-4.82; p <0.001). The independent risk of death factors was being treated in nonhigh complexity centres in oncology hospitals and having started the treatment more than 2 months after diagnosis (adjHR = 1.80; 95% CI: 1.26-2.56; p <0.001) and (adjHR = 2.00; 95% CI: 1.33-3.00; p <0.001), respectively. In addition, the patients diagnosed between 2011 and 2015 had a 40% lower risk of death when compared to those diagnosed between 2000 and 2005 (95% CI: 0.38-0.94; p = 0.027). CONCLUSION: The overall survival in curative intent Stage-I lung cancer patients' treatment was associated with the 5-year diagnosis group, the delayed time between diagnosis and treatment and the hospital qualification.

Practical considerations of single-fraction stereotactic ablative radiotherapy to the lung.

Stereotactic ablative radiotherapy (SABR) is a well-established treatment for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC) and pulmonary oligometastases. The use of single-fraction SABR in this setting is supported by excellent local control and safety profiles which appear equivalent to multi-fraction SABR based on the available data. The resource efficiency and reduction in hospital outpatient visits associated with single-fraction SABR have been particularly advantageous during the COVID-19 pandemic. Despite the increased interest, single-fraction SABR in subgroups of patients remains controversial, including those with centrally located tumours, synchronous targets, proximity to dose-limiting organs at risk, and concomitant severe respiratory illness. This review provides an overview of the published randomised evidence evaluating single-fraction SABR in primary lung cancer and pulmonary oligometastases, the common clinical challenges faced, immunogenic effect of SABR, as well as technical and cost-utility considerations.

Unmet needs in the management of unresectable stage III non-small cell lung cancer: a review after the 'radio talk' webinars.

INTRODUCTION: Stage III non-small cell lung cancer (NSCLC) is a variable entity, encompassing bulky primary tumors, nodal involvement, or both. Multidisciplinary evaluation is essential to discuss multiple treatment options, to outline optimal management, and to examine the main debated topics and critical issues not addressed by current trials and guidelines that influence daily clinical practice. AREAS COVERED: From March to 5 May 2021 ,meetings were scheduled in a webinar format titled 'Radio Talk' due to the COVID-19 pandemic; the faculty was composed of 6 radiation oncologists from 6 different Institutions of Italy, all of them were the referring radiation oncologist for lung cancer treatment at their respective departments and were or had been members of AIRO (Italian Association of Radiation Oncology) Thoracic Oncology Study Group. The topics covered included: pulmonary toxicity, cardiac toxicity, radiotherapy dose, fractionation and volumes, unfit/elderly patients, multidisciplinary management. EXPERT OPINION: The debate was focused on the unmet needs triggered by case reports, personal experiences and questions; the answers were often not univocal; however, the exchange of opinion and the contribution of different centers confirmed the role of multidisciplinary management and the necessity that the most critical issues should be investigated in clinical trials.

Technical aspects of the use of cytopathological specimens for diagnosis and predictive testing in malignant epithelial neoplasms of the lung.

Lung cancer is a leading cause of cancer mortality worldwide but recent years have seen a rapidly rising proportion of cases of advanced non-small cell carcinoma amenable to increasingly targeted therapy, initially based on the differential response to systemic treatment of tumours of squamous or glandular differentiation. In two-thirds of the cases, where patients present with advanced disease, both primary pathological diagnosis and biomarker testing is based on small biopsies and cytopathological specimens. The framework of this article is an overview of the technical aspect of each stage of the specimen pathway with emphasis on maximising potential for success when using small cytology samples. It brings together the current literature addressing pre-analytical and analytical aspects of specimen acquisition, performing rapid onsite evaluation, and undertaking diagnostic and predictive testing using immunocytochemistry and molecular platforms. The advantages and drawbacks of performing analysis on cell block and non-cell block specimen preparations is discussed.

Economic Evaluation of First-Line Camrelizumab for Advanced Non-small-cell Lung Cancer in China.

Background: As the first domestic PD-1 antibody approved for lung cancer in China, camrelizumab has exhibited proven effectiveness for non-small-cell lung cancer (NSCLC) patients. However, the cost-effectiveness of this new regimen remains to be investigated. Objective: To evaluate the cost-effectiveness of camrelizumab combination therapy vs. chemotherapy for previously untreated patients with advanced, non-squamous NSCLC without Alk or Egfr genomic aberrations from the perspective of China's healthcare system. Methods: Based on the CameL trial, the study developed a three-health state Markov model to evaluate the cost-effectiveness of adding camrelizumab to chemotherapy compared to chemotherapy alone in NSCLC patients. The analysis models were conducted for patients unselected by PD-L1 tumor expression (the base case) and the patient subgroup with PD-L1-expressing tumors (≥1%). Primary model outcomes included the costs in US dollars and health outcomes in quality-adjusted life-years (QALYs) as well as the incremental cost-effectiveness ratio (ICER) under a willingness-to-pay threshold of $31,500 per QALY. Additionally, a scenario analysis that adjusted within-trial crossover was employed to evaluate camrelizumab combination therapy compared to chemotherapy without subsequent use of PD1/PD-L1 antibodies. Results: Camrelizumab combination therapy was more costly and provided additional 0.11 QALYs over chemotherapy in the base case analysis (0.86 vs. 0.75 QALYs), 0.12 QALYs over chemotherapy in the subgroup analysis (0.99 vs. 0.88 QALYs), and 0.34 QALYs over chemotherapy in the scenario analysis (0.86 vs. 0.52 QALYs). Correspondingly, the ICER was $63,080 per QALY, $46,311 per QALY, and $30,591 per QALY, in the base case, the subgroup, and the scenario analysis, respectively. One-way sensitivity analyses revealed that ICERs of the base case and the subgroup analysis were most sensitive to the cost of camrelizumab, the cost of pemetrexed. Besides, the base case and subgroup analysis were more sensitive to the risk of neutrophil count decreased in the camrelizumab and the utility of stable disease, respectively. Conclusion: Although camrelizumab combination therapy is not cost-effective as first-line therapy for NSCLC patients in China in the base case, adjusting within-trial crossover would move the treatment regimen toward cost-effectiveness in the scenario analysis.

Experiences of the combined use of Favipiravir in patients using Lorlatinib and Brigatinib.

INTRODUCTION: The SARS-COV-2 (COVID-19) pandemic is challenging the management of cancer patients. In this article, we present two patients diagnosed with anaplastic lymphoma kinase (ALK) + non-small cell lung adenocarcinoma (NSCL CA), infected with COVID-19, who had a previous multi-line therapy with Brigatinib and Lorlatinib, and received Favipiravir for their current infection. CASE REPORTS: A 58-year-old man and a 65-year-old woman were diagnosed as ALK ( + ) NSCL CA. Both patients received tyrosine kinase inhibitors (TKI) for lung cancer when diagnosed with COVID-19. No adverse effects were observed with the concurrent use of Favipiravir, an antiviral drug currently used for COVID-19 and TKI. MANAGEMENT AND OUTCOME: Considering the pharmacokinetic effects of favipiravir and the ALK inhibitor TKI's used on our cases (Brigatinib-Lorlatinib), the concurrent use of these drugs was safe and prevented the delay in the primary treatment of the malignancy of our patients. DISCUSSION: To our knowledge, these are the only reported cases diagnosed as ALK ( + ) NSCL CA who received favipiravir because of COVID-19 while using TKI, and both patients recovered completely without any side effects.

Patterns of Pretreatment Diagnostic Assessment in Patients Treated with Stereotactic Body Radiation Therapy (SBRT) for Non-Small Cell Lung Cancer (NSCLC): Special Characteristics in the COVID Pandemic and Influence on Outcomes.

The pandemic raised a discussion about the postponement of medical interventions for non-small cell lung cancer (NSCLC). We analyzed the characteristics of pretreatment diagnostic assessment in the pandemic and the influence of diagnostic assessment on outcomes. A total of 96 patients with stereotactic body radiation therapy (SBRT) for NSCLC were included. The number of patients increased from mean 0.9 (2012-2019) to 1.45 per month in the COVID era (p < 0.05). Pandemic-related factors (contact reduction, limited intensive care unit resources) might have influenced clinical decision making towards SBRT. The time from pretreatment assessment (multidisciplinary tumor board decision, bronchoscopy, planning CT) to SBRT was longer during the COVID period (p < 0.05). Reduced services, staff shortage, or appointment management to mitigate infection risks might explain this finding. Overall survival, progression-free survival, locoregional progression-free survival, and distant progression-free survival were superior in patients who received a PET/CT scan prior to SBRT (p < 0.05). This supports that SBRT guidelines advocate the acquisition of a PET/CT scan. A longer time from PET/CT scan/conventional staging to SBRT (<10 vs. ≥10 weeks) was associated with worse locoregional control (p < 0.05). The postponement of diagnostic or therapeutic measures in the pandemic should be discussed cautiously. Patient- and tumor-related features should be evaluated in detail.

Postoperative Radiotherapy for Locally Advanced NSCLC: Implications for Shifting to Conformal, High-Risk Fields.

BACKGROUND: To examine the effect of radiotherapy field size on survival outcomes and patterns of recurrence in patients treated with postoperative radiotherapy (PORT) for non-small-cell lung cancer (NSCLC). METHODS: We retrospectively reviewed the records of 216 patients with T1-4 N1-2 NSCLC following surgery and PORT using whole mediastinum (WM) or high-risk (HR) nodal fields from 1998 to 2015. Survival rates were calculated using the Kaplan-Meier method. Univariate and multivariable analyses were conducted using Cox proportional hazards modeling for outcomes and logistic regression analysis for treatment toxicities. RESULTS: Median follow-up was 28 months (interquartile range [IQR] 13-75 months) and 38 months (IQR 19-73 months) for WM (n = 131) and HR (n = 84) groups, respectively. Overall survival (OS) was not significantly different between groups (median OS: HR 49 vs. WM 32 months; P = .08). There was no difference in progression-free survival (PFS), freedom from locoregional recurrence (LRR), or freedom from distant metastasis (P > .2 for all). Field size was not associated with OS, PFS, or LRR (P > .40 for all). LRR rates were 20% for HR and 26% for WM groups (P = .30). There was no significant difference in patterns of initial site of LRR between groups (P > .1). WM fields (OR 3.73, P = .001) and concurrent chemotherapy (odds ratio 3.62, P = .001) were associated with grade ≥2 toxicity. CONCLUSIONS: Locoregional control and survival rates were similar between PORT groups; an improved toxicity profile was observed in the HR group. Results from an ongoing prospective randomized clinical trial will provide further insight into the consequences of HR PORT fields.

SARS-CoV-2 Omicron variant shows less efficient replication and fusion activity when compared with Delta variant in TMPRSS2-expressed cells.

The novel SARS-CoV-2 Omicron variant (B.1.1.529), first found in early November 2021, has sparked considerable global concern and it has >50 mutations, many of which are known to affect transmissibility or cause immune escape. In this study, we sought to investigate the virological characteristics of the Omicron variant and compared it with the Delta variant which has dominated the world since mid-2021. Omicron variant replicated more slowly than the Delta variant in transmembrane serine protease 2 (TMPRSS2)-overexpressing VeroE6 (VeroE6/TMPRSS2) cells. Notably, the Delta variant replicated well in Calu3 cell line which has robust TMPRSS2 expression, while the Omicron variant replicated poorly in this cell line. Competition assay showed that Delta variant outcompeted Omicron variant in VeroE6/TMPRSS2 and Calu3 cells. To confirm the difference in entry pathway between the Omicron and Delta variants, we assessed the antiviral effect of bafilomycin A1, chloroquine (inhibiting endocytic pathway), and camostat (inhibiting TMPRSS2 pathway). Camostat potently inhibited the Delta variant but not the Omicron variant, while bafilomycin A1 and chloroquine could inhibit both Omicron and Delta variants. Moreover, the Omicron variant also showed weaker cell-cell fusion activity when compared with Delta variant in VeroE6/TMPRSS2 cells. Collectively, our results suggest that Omicron variant infection is not enhanced by TMPRSS2 but is largely mediated via the endocytic pathway. The difference in entry pathway between Omicron and Delta variants may have an implication on the clinical manifestations or disease severity.

Salvage pulmonary resection in stages IIIb-IV lung cancer after treatment with immune checkpoint inhibitors case series and literature review.

BACKGROUND AND OBJECTIVES: The role of salvage thoracic surgery in managing advanced-stage lung cancer following treatment with immune checkpoint inhibitors is currently unclear. We present a series of nine patients with advanced non-small-cell lung cancer who underwent pulmonary resection following treatment with pembrolizumab. METHODS: We performed a single-institution retrospective analysis of pulmonary resection undertaken following treatment with pembrolizumab for advanced-stage lung cancer. Nine patients met the inclusion criteria. RESULTS: In six cases, surgery was indicated for persistent localized disease after treatment, and in three cases for nonresponsive synchronous/metachronous lung nodules while on treatment for stage IV lung cancer. Dense hilar fibrosis was present in all patients. Minimal access surgery was achieved in five cases (video-assisted n = 2, robotic-assisted n = 3). There was no in-hospital mortality. One patient died within 60 days from community-acquired COVID-19 pneumonitis. Seven patients remain free of disease between 5 and 22 months follow-up. CONCLUSIONS: Pulmonary resection is safe and technically feasible following treatment with immune checkpoint inhibitors. Surgical challenges relate to postimmunotherapy fibrosis, but with increased experience and a robotic approach, minimal access surgery is achievable. Further prospective studies are required to assess the surgical impact on disease control and overall survival in this patient cohort.

Drug interaction profile of TKI alectinib allows effective and safe treatment of ALK+ lung cancer in the kidney transplant recipient.

ALK targeting with tyrosine kinase inhibitors (TKIs) is a highly potent treatment option for the therapy of ALK positive non-small cell lung cancer (NSCLC). However, pharmacokinetics of TKIs leads to clinically significant drug interactions, and the interfering co-medication may hamper the anti-cancer therapeutic management. Here, we present for the first time a drug interaction profile of ALK-TKIs, crizotinib and alectinib, and immunosuppressive agent cyclosporine A in kidney transplant recipients diagnosed with ALK+ lung cancer. Based on therapeutic drug monitoring of cyclosporin A plasma level, the dose of cyclosporine A has been adjusted to achieve a safe and effective therapeutic level in terms of both cancer treatment and kidney transplant condition. Particularly, 15 years upon the kidney transplantation, the stage IV lung cancer patient was treated with the 1st-line chemotherapy, the 2nd-line ALK-TKI crizotinib followed by ALK-TKI alectinib. The successful therapy with ALK-TKIs has been continuing for more than 36 months, including the period when the patient was treated for COVID-19 bilateral pneumonia. Hence, the therapy of ALK+ NSCLC with ALK-TKIs in organ transplant recipients treated with cyclosporine A may be feasible and effective.

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as mortality predictor of advanced stage non-small cell lung cancer (NSCLC) with COVID-19 in Indonesia.

OBJECTIVE: This study aimed to compare the mortality rate between advanced-stage non-small cell lung cancer patients (NSCLC) with and without COVID-19. This study also explores the possible laboratory characteristics used for prognostication in patients with NSCLC and COVID-19. Additionally, this study evaluated potential differences in laboratory values between the case and control groups. PATIENTS AND METHODS: This is a single-center retrospective cohort study conducted in Dharmais National Cancer Hospital, Indonesia, enrolling patients with NSCLC undergoing chemotherapy or targeted therapy between May 2020 and January 2021. All patients with NSCLC and COVID-19 in these periods were enrolled into the case group. The control group was age-matched NSCLC patients without COVID-19 that was derived from the NSCLC cohort through randomization. RESULTS: There were 342 patients with NSCLC between May 2020 and January 2021. Twenty-seven (7.9%) of the patients were infected by COVID-19. To facilitate comparison, thirty-five age-matched controls with NSCLC were selected from the cohort. The mortality rate in patients with COVID-19 was 46.2%. Eleven patients (40.7%) had severe COVID-19, of which none survived. NLR >8.35 has a sensitivity of 83.3%, specificity of 92.9%, LR+ of 12, and LR- of 0.18. The AUC was 0.946 (95% CI 0.867-1.000), p<0.001. PLR >29.14 has a sensitivity of 75.0%, specificity of 71.4%, LR+ 2.62, LR- 0.35, and AUC 0.851 (95% CI 0.706-0.996), p=0.002. Both NLR and PLR were associated with shorter time-to-mortality in the unadjusted and adjusted model CONCLUSIONS: NLR and PLR are independent predictors of mortality in COVID-19 patients with NSCLC.

Estimating the Impact of Extended Delay to Surgery for Stage I Non-small-cell Lung Cancer on Survival.

OBJECTIVE: The purpose of this study is to evaluate the impact of extended delay to surgery for stage I NSCLC. SUMMARY OF BACKGROUND DATA: During the COVID-19 pandemic, patients with NSCLC may experience delays in care, and some national guidelines recommend delays in surgery by >3 months for early NSCLC. METHODS: Using data from the National Lung Screening Trial, a multi-center randomized trial, and the National Cancer Data Base, a multi-institutional oncology registry, the impact of "early" versus "delayed" surgery (surgery received 0-30 vs 90-120 days after diagnosis) for stage I lung adenocarcinoma and squamous cell carcinoma (SCC) was assessed using multivariable Cox regression analysis with penalized smoothing spline functions and propensity score-matched analyses. RESULTS: In Cox regression analysis of the National Lung Screening Trial (n = 452) and National Cancer Data Base (n = 80,086) cohorts, an increase in the hazard ratio was seen the longer surgery was delayed. In propensity score-matched analysis, no significant differences in survival were found between early and delayed surgery for stage IA1 adenocarcinoma and IA1-IA3 SCC (all P > 0.13). For stage IA2-IB adenocarcinoma and IB SCC, delayed surgery was associated with worse survival (all P < 0.004). CONCLUSIONS: The mortality risk associated with an extended delay to surgery differs across patient subgroups, and difficult decisions to delay care during the COVID-19 pandemic should take substage and histologic subtype into consideration.

Neoadjuvant PD-1 Inhibitors and Chemotherapy for Locally Advanced NSCLC: A Retrospective Study.

BACKGROUND: Stage III non-small cell lung cancer (NSCLC) encompasses a variety of local invasion and nodal involvement and its management is still under debate. Immune checkpoint inhibitors (ICIs) have been shown to improve the survival in metastatic NSCLC, but are far from being accepted as an induction therapy. METHODS: We retrospectively collected data of all patients who received induction ICIs (nivolumab or pembrolizumab) and chemotherapy (carboplatin with paclitaxel) for stage IIIA-B NSCLC followed by surgery in our unit between January 2019 and March 2020. RESULTS: Of the 12 patients (9 men, 3 women) 6 had a squamous cell carcinoma, 4 had adenocarcinoma, 1 had an undifferentiated adenocarcinoma, and 1 had adeno-squamous carcinoma. Seven patients had stage IIIA disease and 5 had stage IIIB. After induction therapy, 6 patients had stable disease and 6 had a partial response. The median tumor reduction was 3.05 cm (range, 2.30-8.70 cm). All patients, but 1 due to the COVID-19 outbreak, had no delay in surgery. Two patients experienced myelosuppression after induction therapy, 2 had minor adverse effects. Three patients had postoperative complications not related to the induction therapy. All patients had a pathologic response: 5 complete, 4 major, and 3 partial. Eleven patients are alive (mean follow-up, 18.17 ± 4.97 months) and free of disease. CONCLUSIONS: Induction ICI chemotherapy may be a valid treatment in patients with locally advanced NSCLC, providing important tumor downstaging and rendering patients operable. In our experience patients had few side effects and a good pathologic response.