Effect of prior antibiotic or chemotherapy treatment on immunotherapy response in non-small cell lung cancer.

BACKGROUND: Treatment outcomes of advanced non-small cell lung cancer (NSCLC) have substantially improved with immune checkpoint inhibitors (ICI), although only approximately 19% of patients respond to immunotherapy alone, increasing to 58% with the addition of chemotherapy. The gut microbiome has been recognized as a modulator of ICI response via its priming effect on the host immune response. Antibiotics as well as chemotherapy reduce gut microbial diversity, hence altering composition and function of the gut microbiome. Since the gut microbiome may modify ICI efficacy, we conducted a retrospective study evaluating the effects of prior antibiotic or chemotherapy use on NSCLC patient response to ICI. METHODS: We retrospectively evaluated 256 NSCLC patients treated between 2011-2017 at Moffitt Cancer Center with ICI ± chemotherapy, examining the associations between prior antibiotic or chemotherapy use, overall response rate and survival. Relative risk regression using a log-link with combinatorial expectation maximization algorithm was performed to analyze differences in response between patients treated with antibiotics or chemotherapy versus patients who didn't receive antibiotics or chemotherapy. Cox proportional hazards models were constructed to evaluate associations between risk factors and overall survival. RESULTS: Only 46 (18% of 256) patients used antibiotics prior to and/or during ICI treatment, and 146 (57%) had prior chemotherapy. Antibiotic users were 8% more likely to have worse overall response rate (RR:1.08; CI:0.93-1.26; p = 0.321), as well as a 35% worse overall survival (HR:1.35; CI:0.91-2.02; p = 0.145), although results were not statistically significant. However, prior use of chemotherapy was significantly associated with poor ICI response (RR:1.24; CI:1.05-1.47; p = 0.013) and worse overall survival (HR:1.47; CI:1.07-2.03; p = 0.018). CONCLUSIONS: Patients receiving antibiotics prior to and/or during ICI therapy might experience worse treatment outcomes and survival than unexposed patients, although these associations were not statistically significant and hence warrant further prospective study. Prior chemotherapy significantly reduced ICI response and overall survival. Antibiotic or chemotherapy exposure may negatively impact ICI response, perhaps through disruption of the eubiotic gut microbiome.

Emerging Approaches to Complement Low-Dose Computerized Tomography for Lung Cancer Screening: A Narrative Review.

Lung cancer screening by low-dose computed tomography (LDCT) can save lives. Nevertheless, the test suffers from low accuracy. Improving its accuracy will reduce unnecessary invasive procedures and allow lung cancer treatment to be delivered sooner. This review describes the principles, advantages, and disadvantages of selected emerging modalities potentially useful to improve the accuracy of LDCT. A literature search was conducted using PubMed and Google scholar for relevant publications. We identified four key emerging approaches: radiomics, breath analysis, urine test, and blood test. Radiomics, which uses a computer program to extract various radiological features from radiographic images, holds the potential to improve the accuracy of LDCT. However, to date, there remains no adequately validated system. Breath analysis and urine tests represent a noninvasive and convenient means of screening by detecting substances such as volatile organic compounds associated with lung cancer. However, the results can be confounded by diets, medications, and concurrent medical conditions. Finally, a blood test to screen for protein biomarkers or methylation profiles such as Galleri® has high specificity. However, its sensitivity is low, especially for detecting early-stage lung cancer. Furthermore, the cost for mass public use can be significant. Based on our review, blood tests may have potential for future clinical utility. Its high specificity may be useful to rule in a suspicious lung nodule as malignant, so that other additional tests can be omitted. Data from a well-designed clinical trial will be needed to understand the clinical utility of this strategy.

Outcomes of Intraocular Metastasis From Lung Cancer in the Era of Targeted Therapy: A Systematic Review and Pooled Analysis.

INTRODUCTION: Metastasis to intraocular structures is a serious problem in lung cancer. Due to its rarity, however, limited information is available regarding the outcomes of treatment and prognosis. Literature often suggests a poor prognosis. We review current literature on the outcomes of systemic therapy and prognostic factors. METHODS: We conducted a systematic review of English literature published during 2009 to 2022 identified via Medline and Google Scholar search. Publications reporting on tumor response in the eyes or overall survival of patients with intraocular metastasis due to lung cancer were included. Pooled analysis of patients receiving systemic therapy was performed, utilizing individual-level patient data. RESULTS: A total of 79 publications contributed 92 patients into the analysis. Choroid was the most affected intraocular structure, in 82% of patients. Histology was small cell in 13% and non-small cell in 87%. Targeted therapy was utilized in 45% of patients. A pooled analysis demonstrated that the median overall survival was 27 months (95% CI: 21.8-32.2). Visual response among those with reported assessment showed that 92% of them had stable or improved vision while 8% experienced worsening of vision. Several factors including the year of treatment, age, targeted therapy, and radiation showed a significant association with survival. The strongest predictor of improved survival was the receipt of targeted therapy, with a hazard ratio of 0.31 (95% CI: 0.14-0.71), P = .005. CONCLUSIONS: For lung cancer patients with intraocular metastasis, systemic therapy can produce a favorable outcome. Particularly when a targeted therapy is feasible, long-term survival can be achieved.

Characteristics and Outcomes of Lung Cancer Screening Among Individuals With or Without Cancer History.

BACKGROUND: Lung cancer screening with low-dose computed tomography (LDCT) can reduce mortality from lung cancer. Individuals with previous malignancy are at an increased risk of lung cancer but are often underrepresented in clinical trials. This study compares the outcomes of LDCT screening among individuals with and without cancer history. MATERIALS AND METHODS: The study cohort included consecutive participants undergoing LDCT screening at a tertiary care cancer institution. Abnormal screening result was defined as having Lung-RADS 3 or 4 at baseline (T0). Participant information was prospectively collected and predicted risk of lung cancer was calculated per the PLCOm2012 model. RESULTS: A total of 454 participants underwent LDCT screening. Abnormal screening result occurred in 57 (13.2%) participants at T0, and lung cancer was diagnosed in 11 (2.4%) participants. Among 153 individuals with cancer history, abnormal result occurred in 9.8%, compared with 15.4% among those without cancer history (P = .11). Lung cancer was diagnosed in 1.3%, compared with 3.5% (P = .22). The predicted risk of lung cancer at 6 years was higher among individuals with cancer history than those without: 4.8% versus 2.2% (P < .001). In a multivariable analysis, cancer history significantly reduced the likelihood of abnormal screening (odds ratio, 0.49; 95% confidence interval, 0.26-0.94; P = .03). We observed a higher proportion of participants who had a previous CT scan available for comparison at T0 among individuals with cancer history than those without: 43.1% versus 9.1% (P < .001). CONCLUSIONS: In this single-institutional study, individuals with cancer history were significantly less likely to have abnormal screening results than those without cancer history.

Sweet's syndrome associated with hematological malignancies.

BACKGROUND: Sweet's syndrome, or acute febrile neutrophilic dermatosis, is often mistaken for a skin infection given its similar clinical presentation. OBJECTIVE: To describe the clinical presentations and management of a rare dermatologic condition associated with hematological malignancies. METHODS: Case series; Chart review of patients at Moffitt Cancer Center between 2017 and 2020. RESULTS: The subjects are a 79 year-old man (Patient 1) with Myelodysplastic Syndrome (MDS), a 66 year-old woman (Patient 2) with Acute Myeloid Leukemia (AML), a 56 year-old man (Patient 3) with AML, and a 69 year-old man (Patient 4) with MDS. Patient 1 was initially misdiagnosed with neutropenic fever. Patient 2 was incidentally discovered to have erythematous skin lesions prior to initiating chemotherapy. Before starting second line chemotherapy, patient 3 developed pathergy at the site of a PICC line. Patient 4 developed erythema around a newly placed port before initiating chemotherapy. Only patients 1 and 3 received glucocorticoids. Patients 2, 3, and 4 were able to initiate chemotherapy without further complications. LIMITATIONS: Heterogeneity of subjects in terms of prognostic factors, stage at diagnosis, and treatment strategies. CONCLUSION: Early recognition and treatment of malignancy-associated Sweet's syndrome is imperative to limit patient morbidity and expeditiously provide anti-cancer treatments.

Complete Tumor Response of Tracheal Squamous Cell Carcinoma After Treatment With Pembrolizumab.

Persistent carcinoma of the trachea is an uncommon thoracic malignancy with limited treatment options. To our knowledge pembrolizumab, an immunotherapy targeting programmed death 1, has not been previously reported as an effective therapy for tracheal carcinoma. Here we describe a case of recurrent tracheal squamous cell carcinoma refractory to photodynamic therapy, radiotherapy, and cryotherapy. Programmed death ligand 1 was positive in 90% to 95% of tumor cells. A complete tumor response was observed after three months of treatment with pembrolizumab. No adverse events were reported at the 11-month follow-up. Based on our experience, pembrolizumab represents another viable treatment option for tracheal carcinoma.

Ipilimumab/Nivolumab-related Opsoclonus-Myoclonus-Ataxia Syndrome Variant in a Patient with Malignant Pleural Mesothelioma.

INTRODUCTION: Ipilimumab and nivolumab are immune-checkpoint inhibitors commonly used for melanoma. The combination is being investigated for its efficacy against several types of cancer, including malignant pleural mesothelioma. Although immune-related adverse events have been reported in patients receiving immune-checkpoint inhibitors, opsoclonus-myoclonus-ataxia syndrome has never been previously described. CASE PRESENTATION: We describe a 74-year-old male with malignant pleural mesothelioma who presented with opsoclonus and marked truncal ataxia ∼10 weeks following immunotherapy with ipilimumab and nivolumab. No myoclonus was present. Oligoclonal bands were detected in cerebrospinal fluid. Treatment with methylprednisolone and intravenous immunoglobulin along with clonazepam and valproic acid resulted in a rapid clinical improvement. A follow-up visit 2 months afterward showed a resolution of opsoclonus and he was able to walk with cane. CONCLUSIONS: A variant of opsoclonus-myoclonus-ataxia syndrome may occur following treatment with ipilimumab and nivolumab.