Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC.

BACKGROUND: Among patients with resected, epidermal growth factor receptor (EGFR)-mutated, stage IB to IIIA non-small-cell lung cancer (NSCLC), adjuvant osimertinib therapy, with or without previous adjuvant chemotherapy, resulted in significantly longer disease-free survival than placebo in the ADAURA trial. We report the results of the planned final analysis of overall survival. METHODS: In this phase 3, double-blind trial, we randomly assigned eligible patients in a 1:1 ratio to receive osimertinib (80 mg once daily) or placebo until disease recurrence was observed, the trial regimen was completed (3 years), or a discontinuation criterion was met. The primary end point was investigator-assessed disease-free survival among patients with stage II to IIIA disease. Secondary end points included disease-free survival among patients with stage IB to IIIA disease, overall survival, and safety. RESULTS: Of 682 patients who underwent randomization, 339 received osimertinib and 343 received placebo. Among patients with stage II to IIIA disease, the 5-year overall survival was 85% in the osimertinib group and 73% in the placebo group (overall hazard ratio for death, 0.49; 95.03% confidence interval [CI], 0.33 to 0.73; P<0.001). In the overall population (patients with stage IB to IIIA disease), the 5-year overall survival was 88% in the osimertinib group and 78% in the placebo group (overall hazard ratio for death, 0.49; 95.03% CI, 0.34 to 0.70; P<0.001). One new serious adverse event, pneumonia related to coronavirus disease 2019, was reported after the previously published data-cutoff date (the event was not considered by the investigator to be related to the trial regimen, and the patient fully recovered). Adjuvant osimertinib had a safety profile consistent with that in the primary analysis. CONCLUSIONS: Adjuvant osimertinib provided a significant overall survival benefit among patients with completely resected, EGFR-mutated, stage IB to IIIA NSCLC. (Funded by AstraZeneca; ADAURA ClinicalTrials.gov number, NCT02511106.).

Effects of a 12-Week Multimodal Exercise Intervention Among Older Patients with Advanced Cancer: Results from a Randomized Controlled Trial.

BACKGROUND: Older patients with cancer are at risk of physical decline and impaired quality of life during oncological treatment. Exercise training has the potential to reduce these challenges. The study aim was to investigate the feasibility and effect of a multimodal exercise intervention in older patients with advanced cancer (stages III/IV). PATIENTS AND METHODS: Eighty-four older adults (≥65 years) with advanced pancreatic, biliary tract, or non-small cell lung cancer who received systemic oncological treatment were randomized 1:1 to an intervention group or a control group. The intervention was a 12-week multimodal exercise-based program including supervised exercise twice weekly followed by a protein supplement, a home-based walking program, and nurse-led support and counseling. The primary endpoint was change in physical function (30-second chair stand test) at 13 weeks. RESULTS: Median age of the participants was 72 years (interquartile range [IQR] 68-75). Median adherence to the exercise sessions was 69% (IQR 21-88) and 75% (IQR 33-100) for the walking program. At 13 weeks, there was a significant difference in change scores of 2.4 repetitions in the chair stand test, favoring the intervention group (p < .0001). Furthermore, significant beneficial effects were seen for physical endurance (6-minute walk test), hand grip strength, physical activity, symptom burden, symptoms of depression and anxiety, global health status (quality of life), and lean body mass. No effects were seen for dose intensity, hospitalizations, or survival. CONCLUSION: A 12-week multimodal exercise intervention with targeted support proved effective in improving physical function in older patients with advanced cancer during oncological treatment.

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.

The aggregate index of systemic inflammation may predict mortality in COVID-19 patients with chronic renal failure.

OBJECTIVE: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), was first detected in December 2019 and then spread globally, resulting in a pandemic. Initially, it was unknown if chronic kidney disease (CKD) contributed to the mortality caused by COVID-19. The immunosuppression associated with this disease may minimize the COVID-19-described hyper-inflammatory state or immunological dysfunction, and a high prevalence of comorbidities may lead to a poorer clinical prognosis. Patients with COVID-19 have abnormal circulating blood cells associated with inflammation. Risk stratification, diagnosis, and prognosis primarily rely on hematological features, such as white blood cells and their subpopulations, red cell distribution width, mean platelet volume, and platelet count, in addition to their combined ratios. In non-small-cell lung cancer, the aggregate index of systemic inflammation (AISI), (neutrophils x monocytes x platelets/lymphocytes) is evaluated. In light of the relevance of inflammation in mortality, the objective of this study is to determine the impact of AISI on the hospital mortality of CKD patients. PATIENTS AND METHODS: This study is an observational retrospective study. Data and test outcomes of all CKD patients, stages 3-5, hospitalized for COVID-19 and followed between April and October 2021 were analyzed. RESULTS: Patients were divided into two groups according to death (Group 1-Alive, Group 2-Died). Neutrophil count, AISI and C-reactive protein (CRP) levels were increased in Group-2 [10.3±4.6 vs. 7.65±4.22; p=0.001, 2,084.1 (364.8-2,577.5) vs. 628.9 (53.1-2,275); p=0.00 and 141.9 (20.5-318) vs. 84.75 (0.92-195); p=0.00; respectively]. Receiver operating characteristic (ROC) analysis demonstrated 621.1 as a cut-off value for AISI to predict hospital mortality with 81% sensitivity and 69.1% specificity [area under ROC curve 0.820 (95% CI: 0.733-0.907), p<.005]. Cox regression analysis was used to analyze the effect of risk variables on survival. In survival analysis, AISI and CRP were identified as important survival predictors [hazard ratio (HR): 1.001, 95% CI: 1-1.001; p=0.00 and HR: 1.009, 95% CI: 1.004-1.013; p=0.00]. CONCLUSIONS: This study demonstrated the discriminative effectiveness of AISI in predicting disease mortality in COVID-19 patients with CKD. Quantification of AISI upon admission might assist in the early detection and treatment of individuals with a bad prognosis.

Follow-Up Imaging Guidelines for Patients with Stage III Unresectable NSCLC: Recommendations Based on the PACIFIC Trial.

The PACIFIC trial showed a survival benefit with durvalumab through five years in stage III unresectable non-small cell lung cancer (NSCLC). However, optimal use of imaging to detect disease progression remains unclearly defined for this population. An expert working group convened to consider available evidence and clinical experience and develop recommendations for follow-up imaging after concurrent chemotherapy and radiation therapy (CRT). Voting on agreement was conducted anonymously via online survey. Follow-up imaging was recommended for all suitable patients after CRT completion regardless of whether durvalumab is received. Imaging should occur every 3 months in Year 1, at least every 6 months in Year 2, and at least every 12 months in Years 3-5. Contrast computed tomography was preferred; routine brain imaging was not recommended for asymptomatic patients. The medical oncologist should follow-up during Year 1 of durvalumab therapy, with radiation oncologist involvement if pneumonitis is suspected; medical and radiation oncologists can subsequently alternate follow-up. Some patients can transition to the family physician/community primary care team at the end of Year 2. In Years 1-5, patients should receive information regarding smoking cessation, comorbidity management, vaccinations, and general follow-up care. These recommendations provide guidance on follow-up imaging for patients with stage III unresectable NSCLC whether or not they receive durvalumab consolidation therapy.

Not Feeling Swell: Superior Vena Cava (SVC) Syndrome Falsely Attributed to COVID-19 Vaccine Reaction.

BACKGROUND: The mass immunization campaign against Coronavirus disease 2019 (COVID-19) has resulted in more patients presenting to the emergency department (ED) with concern for a vaccine reaction. CASE REPORT: A 68-year-old man presented to the ED reporting an allergic reaction to the COVID-19 vaccine. He initially noted swelling of his face, neck, and right arm after receiving the first dose of the vaccine. After his second dose of the vaccine, the swelling became more pronounced and prompted him to seek care. On examination, he had fullness of the neck and engorgement of the left external jugular vein, which were exacerbated when the patient raised his arms above his head, consistent with Pemberton's sign. Apart from the swelling of the head and neck, there were no other findings consistent with an allergic reaction. The presence of Pemberton's sign prompted a computed tomography scan of the chest with contrast, which revealed a paratracheal mass measuring 4.5 × 2.0 cm with marked narrowing of the superior vena cava (SVC). The patient was admitted to the hospital for SVC syndrome, and further workup revealed a non-small cell lung cancer. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Patients may misattribute their symptoms to a COVID vaccine reaction when they are, in fact, experiencing a more serious underlying disease. This case highlights the importance of a thorough physical examination and maintaining a broad differential diagnosis. In this case, the presence of Pemberton's sign raised suspicion for SVC syndrome, and prompted further workup.

Risk factors and actionable molecular signatures in COVID-19-associated lung adenocarcinoma and lung squamous cell carcinoma patients.

The molecular mechanism of the pathological impact of COVID-19 in lung cancer patients remains poorly understood to date. In this study, we used differential gene expression pattern analysis to try to figure out the possible disease mechanism of COVID-19 and its associated risk factors in patients with the two most common types of non-small-cell lung cancer, namely, lung adenocarcinoma and lung squamous cell carcinoma. We also used network-based approaches to identify potential diagnostic and molecular targets for COVID-19-infected lung cancer patients. Our study showed that lung cancer and COVID-19 patients share 36 genes that are expressed differently and in common. Most of these genes are expressed in lung tissues and are mostly involved in the pathogenesis of different respiratory tract diseases. Additionally, we also found that COVID-19 may affect the expression of several cancer-associated genes in lung cancer patients, such as the oncogenes JUN, TNC, and POU2AF1. Moreover, our findings suggest that COVID-19 may predispose lung cancer patients to other diseases like acute liver failure and respiratory distress syndrome. Additionally, our findings, in concert with published literature, suggest that molecular signatures, such as hsa-mir-93-5p, CCNB2, IRF1, CD163, and different immune cell-based approaches could help both diagnose and treat this group of patients. Altogether, the scientific findings of this study will help formulate appropriate management measures and guide the development of diagnostic and therapeutic measures for COVID-19-infected lung cancer patients.

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.

Thymosin alpha 1 - Reimagine its broader applications in the immuno-oncology era.

Thymosin alpha 1 (Tα1) is a highly conserved 28 amino-acid peptide naturally occurring in the thymus and plays critical roles in T cell maturity and differentiation. Its synthetic form, thymalfasin, has been approved by various regulatory agencies in the treatment of hepatitis B viral infection and as an enhancer of vaccine response in immune-compromised populations. In China, it has also widely utilized in patients with cancer and severe infections, as well as the emergency use during (Severe Acute Respiratory Syndrome)SARS and COVID-19 pandemic as an immune-regulator. Recent studies showed that Tα1 could significantly improve overall survival (OS) in patients with surgically resectable non-small cell lung cancer (NSCLC) and liver cancers in the adjuvant setting. For patients with locally advanced, unresectable NSCLC, Tα1 could significantly reduce chemoradiation-induced lymphopenia, pneumonia, and trending improvement of OS. Preclinical evidence are emerging to demonstrate that Tα1 may augment efficacy of cancer chemotherapy by reversing efferocytosis-induced M2 polarization of macrophages via activation of a TLR7/SHIP1 axis and enhancing anti-tumor immunity by turning "cold-tumors" to "hot-tumors"; a protective role in reducing colitis caused by immune check-point inhibitors (ICIs). Potential enhancement of ICIs' clinical efficacies has also been indicated. ICIs have transformed ways treating patients with cancer but limitations such as relatively low response rates and certain safety issues remains. Given the roles of Tα1 in regulating cellular immunities and exceptional safety profiles demonstrated in decades clinical uses, we believe that it is plausible to explore implications of Tα1 the immune-oncology setting by combining with ICI-based therapeutic strategies. Background Activities of Tα1. Tα1 is a biological response modifier which activates various cells in the immune system [1-3]. Tα1 is therefore expected to have clinical benefits in disorders where immune responses are impaired or ineffective. These disorders include acute and chronic infections, cancers, and vaccine non-responsiveness. In severe sepsis, for example, sepsis-induced immunosuppression is increasingly recognized as the overriding immune dysfunction in these vulnerable patients [4] and there is now agreement that many patients with severe sepsis survive the first critical hours of the syndrome but eventually die later due to patients' immunosuppression which make the system difficulty to fight the primary bacterial infection, decreased resistance to secondary nosocomial infections, and reactivation of viral infections [5]. Tα1 has been shown to restore immune functions and help to reduce mortality in patients with severe sepsis.

Viral Vectors in Gene Therapy: Where Do We Stand in 2023?

Viral vectors have been used for a broad spectrum of gene therapy for both acute and chronic diseases. In the context of cancer gene therapy, viral vectors expressing anti-tumor, toxic, suicide and immunostimulatory genes, such as cytokines and chemokines, have been applied. Oncolytic viruses, which specifically replicate in and kill tumor cells, have provided tumor eradication, and even cure of cancers in animal models. In a broader meaning, vaccine development against infectious diseases and various cancers has been considered as a type of gene therapy. Especially in the case of COVID-19 vaccines, adenovirus-based vaccines such as ChAdOx1 nCoV-19 and Ad26.COV2.S have demonstrated excellent safety and vaccine efficacy in clinical trials, leading to Emergency Use Authorization in many countries. Viral vectors have shown great promise in the treatment of chronic diseases such as severe combined immunodeficiency (SCID), muscular dystrophy, hemophilia, ß-thalassemia, and sickle cell disease (SCD). Proof-of-concept has been established in preclinical studies in various animal models. Clinical gene therapy trials have confirmed good safety, tolerability, and therapeutic efficacy. Viral-based drugs have been approved for cancer, hematological, metabolic, neurological, and ophthalmological diseases as well as for vaccines. For example, the adenovirus-based drug Gendicine® for non-small-cell lung cancer, the reovirus-based drug Reolysin® for ovarian cancer, the oncolytic HSV T-VEC for melanoma, lentivirus-based treatment of ADA-SCID disease, and the rhabdovirus-based vaccine Ervebo against Ebola virus disease have been approved for human use.

Impact of extended interval dosing of immune checkpoint inhibitors in lung cancer patients during the COVID-19 pandemic.

BACKGROUND: The COVID 19-pandemic has led physicians to change their approach to treating non-small cell lung cancer (NSCLC) to reduce hospital stays for patients. OBJECTIVES: We aimed to assess the toxicity and efficacy of extended interval (EI) dosing of immune checkpoint inhibitors (ICIs) compared to standard dosing (SD). METHODS: In this retrospective two-center study, we included patients with stage III/IV NSCLC who were treated with ICIs with or without maintenance pemetrexed during the month before March 2020. Adverse events and efficacy were collected until June 2021. Toxicity and survival were assessed using multivariate Cox models. RESULTS: Among the 134 patients identified (8 stage III and 126 stage IV; 66 first line and 60 second or subsequent lines), 70.9% received EI dosing. In the EI group, 12.6% of patients developed grade 3 or 4 immune-related adverse events versus 15.4% in the SD group (P- value = 0.8). Treatment was definitively discontinued due to toxicity in 9 patients in the EI group and in 5 in the SD group (P-value =0.5). Overall survival was not associated with dosage regimen or toxicity analyzed as a time-dependent variable. CONCLUSIONS: Our study suggests that EI dosing of ICIs did not affect toxicity and overall survival in lung cancer patients.

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis.

INTRODUCTION: Pembrolizumab (Keytruda) is a monoclonal antibody against the programmed cell death-1 (PD-1) receptor on lymphocytes, which is one of the immune checkpoint inhibitors (ICIs) approved for multiple solid and hematologic malignancies. Although ICIs have proven to be more effective and less toxic compared to chemotherapy, there are reports of adverse side effects with ICIs. For example, pneumonitis is a potentially lethal side effect occurring in 1%-5% of patients who received ICIs in clinical trials, and there are case reports with clinical and radiological features of checkpoint inhibitor-pneumonitis (CIP). CASE REPORT: We report an unusual case of pneumonitis with atypical imaging in a patient who received pembrolizumab for metastatic p16-positive squamous cell carcinoma of the base of the tongue. We discuss the approach to the recognition and management of atypical CIP in patients on pembrolizumab with the intent to standardize workup and increase awareness among healthcare providers in the new era of immunotherapy. MANAGEMENT AND OUTCOME: Serologic workup including laboratory studies for complete blood count (CBC), lactate, procalcitonin, SARS-CoV-2 (COVID-19), Legionella, Cytomegalovirus (CMV), Coccidioides, Coxiella, and viral respiratory panel were negative for infectious processes. Since CIP was suspected, the patient was started on steroid therapy. Interval computed tomography (CT) of the chest without contrast showed a resolution of pneumonitis. DISCUSSION: In this case report, we discuss our workup of CIP and initial testing to rule out other possible causes of the patient's symptoms and radiographic findings, and management of the patient's diagnosis of atypical CIP which led to complete clinical recovery from CIP.

The Impact of COVID-19 on Lung Cancer Incidence in England: Analysis of the National Lung Cancer Audit 2019 and 2020 Rapid Cancer Registration Datasets.

BACKGROUND: The COVID-19 pandemic has caused significant disruption to health-care services and delivery worldwide. The impact of the pandemic and associated national lockdowns on lung cancer incidence in England have yet to be assessed. RESEARCH QUESTION: What was the impact of the first year of the COVID-19 pandemic on the incidence and presentation of lung cancer in England? STUDY DESIGN AND METHODS: In this retrospective observational study, incidence rates for lung cancer were calculated from The National Lung Cancer Audit Rapid Cancer Registration Datasets for 2019 and 2020, using midyear population estimates from the Office of National Statistics as the denominators. Rates were compared using Poisson regression according to time points related to national lockdowns in 2020. RESULTS: Sixty-four thousand four hundred fifty-seven patients received a diagnosis of lung cancer across 2019 (n = 33,088) and 2020 (n = 31,369). During the first national lockdown, a 26% reduction in lung cancer incidence was observed compared with the equivalent calendar period of 2019 (adjusted incidence rate ratio [IRR], 0.74; 95% CI, 0.71-0.78). This included a 23% reduction in non-small cell lung cancer (adjusted IRR, 0.77; 95% CI, 0.74-0.81) and a 45% reduction in small cell lung cancer (adjusted IRR, 0.55; 95% CI, 0.46-0.65) incidence. Thereafter, incidence rates almost recovered to baseline, without overcompensation (adjusted IRR, 0.96; 95% CI, 0.94-0.98). INTERPRETATION: The incidence rates of lung cancer in England fell significantly by 26% during the first national lockdown in 2020 and did not compensate later in the year.

N-Containing α-Mangostin Analogs via Smiles Rearrangement as the Promising Cytotoxic, Antitrypanosomal, and SARS-CoV-2 Main Protease Inhibitory Agents.

New N-containing xanthone analogs of α-mangostin were synthesized via one-pot Smiles rearrangement. Using cesium carbonate in the presence of 2-chloroacetamide and catalytic potassium iodide, α-mangostin (1) was subsequently transformed in three steps to provide ether 2, amide 3, and amine 4 in good yields at an optimum ratio of 1:3:3, respectively. The evaluation of the biological activities of α-mangostin and analogs 2-4 was described. Amine 4 showed promising cytotoxicity against the non-small-cell lung cancer H460 cell line fourfold more potent than that of cisplatin. Both compounds 3 and 4 possessed antitrypanosomal properties against Trypanosoma brucei rhodesiense at a potency threefold stronger than that of α-mangostin. Furthermore, ether 2 gave potent SARS-CoV-2 main protease inhibition by suppressing 3-chymotrypsinlike protease (3CLpro) activity approximately threefold better than that of 1. Fragment molecular orbital method (FMO-RIMP2/PCM) indicated the improved binding interaction of 2 in the 3CLpro active site regarding an additional ether moiety. Thus, the series of N-containing α-mangostin analogs prospectively enhance druglike properties based on isosteric replacement and would be further studied as potential biotically active chemical entries, particularly for anti-lung-cancer, antitrypanosomal, and anti-SARS-CoV-2 main protease applications.

Impact of COVID-19 Pandemic on Non-Small Cell Lung Cancer Care.

We assessed the impact of COVID-19 on healthcare visits, timing of stage IV NSCLC diagnosis and immunotherapy initiation, and rates of switching to extended dosing schedules of immunotherapies among patients with stage IV NSCLC. This retrospective study examined electronic health record data of adult patients receiving treatment for stage IV NSCLC within The US Oncology Network and Onmark. Endpoints were compared for February-July 2019 (before COVID) vs. February-July 2020 (during COVID). The study found rapid decreases in numbers of patients with clinic/vital visits, immunotherapy initiations, and new diagnoses of stage IV NSCLC during April-May 2020 vs. April-May 2019. The rate of delays of immunotherapy administrations and proportions of patients with such delays increased from February to March of 2020. These patterns may have resulted from the increase in COVID-19 cases during this period and the corresponding quarantine and lockdowns. However, when comparing pre COVID-19 and during COVID-19 for May and after, the differences in delay of immuno-oncology administrations became less marked, likely due to lifting of lockdowns. The rate of switching from shorter to longer dosing schedules increased from May-July 2020. This was mainly attributed to pembrolizumab, likely due to FDA approval of the pembrolizumab 6W dosing schedule in April 2020.

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.

Survival outcomes following treatment delays among patients with early-stage female cancers: a nationwide study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) severely hindered the timely receipt of health care for patients with cancer, especially female patients. Depression and anxiety were more pronounced in female patients than their male counterparts with cancer during treatment wait-time intervals. Herein, investigating the impact of treatment delays on the survival outcomes of female patients with early-stage cancers can enhance the rational and precise clinical decisions of physicians. METHODS: We analyzed five types of cancers in women from the Surveillance, Epidemiology, and End Results (SEER) program between Jan 2010 and Dec 2015. Univariate and multivariate Cox regression analyses were used to determine the impacts of treatment delays on the overall survival (OS) and cancer-specific survival (CSS) of the patients. RESULTS: A total of 241,661 females with early-stage cancer were analyzed (12,617 cases of non-small cell lung cancer (NSCLC), 166,051 cases of infiltrating breast cancer, 31,096 cases of differentiated thyroid cancer, 23,550 cases of colorectal cancer, and 8347 cases of cervical cancer). Worse OS rates were observed in patients with treatment delays ≥ 3 months in stage I NSCLC (adjustedHazard ratio (HR) = 1.11, 95% Confidence Interval (CI): 1.01-1.23, p = 0.044) and stage I infiltrating breast cancer (adjustedHR = 1.23, 95% CI 1.11-1.37, p < 0.001). When the treatment delay intervals were analyzed as continuous variables, similar results were observed in patients with stage I NSCLC (adjustedHR = 1.04, 95% CI 1.01-1.06, p = 0.010) and in those with stage I breast cancer (adjustedHR = 1.03, 95% CI 1.00-1.06, p = 0.029). However, treatment delays did not reduce the OS of patients with differentiated thyroid cancer, cervical cancer, or colorectal cancer in the early-stage. Only intermediate treatment delays impaired the CSS of patients with cervical cancer in stage I (adjustedHR = 1.31, 95% CI 1.02-1.68, p = 0.032). CONCLUSION: After adjusting for confounders, the prolonged time from diagnosis to the initiation of treatment (< 6 months) showed limited negative effects on the survival of most of the patients with early-stage female cancers. Whether our findings serve as evidence supporting the treatment deferral decisions of clinicians for patients with different cancers in resource-limited situations needs further validation.

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.

Antibody Response to COVID-19 mRNA Vaccine in Patients With Lung Cancer After Primary Immunization and Booster: Reactivity to the SARS-CoV-2 WT Virus and Omicron Variant.

PURPOSE: To examine COVID-19 mRNA vaccine-induced binding and neutralizing antibody responses in patients with non-small-cell lung cancer (NSCLC) to SARS-CoV-2 614D (wild type [WT]) strain and variants of concern after the primary 2-dose and booster vaccination. METHODS: Eighty-two patients with NSCLC and 53 healthy volunteers who received SARS-CoV-2 mRNA vaccines were included in the study. Blood was collected longitudinally, and SARS-CoV-2-specific binding and neutralizing antibody responses were evaluated by Meso Scale Discovery assay and live virus Focus Reduction Neutralization Assay, respectively. RESULTS: A majority of patients with NSCLC generated binding and neutralizing antibody titers comparable with the healthy vaccinees after mRNA vaccination, but a subset of patients with NSCLC (25%) made poor responses, resulting in overall lower (six- to seven-fold) titers compared with the healthy cohort (P = < .0001). Although patients age > 70 years had lower immunoglobulin G titers (P = < .01), patients receiving programmed death-1 monotherapy, chemotherapy, or a combination of both did not have a significant impact on the antibody response. Neutralizing antibody titers to the B.1.617.2 (Delta), B.1.351 (Beta), and in particular, B.1.1.529 (Omicron) variants were significantly lower (P = < .0001) compared with the 614D (WT) strain. Booster vaccination led to a significant increase (P = .0001) in the binding and neutralizing antibody titers to the WT and Omicron variant. However, 2-4 months after the booster, we observed a five- to seven-fold decrease in neutralizing titers to WT and Omicron viruses. CONCLUSION: A subset of patients with NSCLC responded poorly to the SARS-CoV-2 mRNA vaccination and had low neutralizing antibodies to the B.1.1.529 Omicron variant. Booster vaccination increased binding and neutralizing antibody titers to Omicron, but antibody titers declined after 3 months. These data highlight the concern for patients with cancer given the rapid spread of SARS-CoV-2 Omicron variant.

Severe Post-COVID-19 Organizing Pneumonia during Cancer Immunochemotherapy.

A 44-year-old man developed coronavirus disease 2019 (COVID-19) pneumonia during immunochemotherapy consisting of carboplatin, paclitaxel, and pembrolizumab for non-small cell lung cancer. Low-grade fever, followed by mild hypoxemia, and febrile neutropenia, were observed, and granulocyte colony-stimulating factor (G-CSF) was administered until the recovery of neutropenia, when he developed a high fever, severe hypoxemia, and hypotension accompanied by consolidation in the bilateral lungs. His conditions promptly improved after treatment including hydrocortisone and the primary and metastatic tumors remained regressed for 10 months without further treatment. Post-COVID-19 organizing pneumonia during cancer immunochemotherapy can be aggravated by immune-checkpoint inhibitors and G-CSF.