A Patient with Four-Year Survival after Nonsmall Cell Lung Carcinoma with a Solitary Metachronous Small Bowel Metastasis

Solitary small bowel metastasis secondary to lung cancer is very uncommon. In this report, we present a patient with NSCLC and a metachronous solitary metastasis of the jejunum. She is alive without evidence of disease and doing well four years after palliative surgery, radiotherapy, and chemotherapy. To the best of our knowledge, this is the first case report describing a prolonged survival in a patient with a symptomatic solitary small bowel metastasis treated with palliative surgery, chemo- and radiotherapy instead of complete surgical resection

Current State of Dendritic Cell-Based Immunotherapy: Opportunities for in vitro Antigen Loading of Different DC Subsets?

Dendritic cell (DC) based cancer immunotherapy aims at the activation of the immune system, and in particular tumor-specific cytotoxic T lymphocytes (CTLs) to eradicate the tumor. DCs represent a heterogeneous cell population, including conventional DCs (cDCs), consisting of cDC1s, cDC2s, plasmacytoid DCs (pDCs), and monocyte-derived DCs (moDCs). These DC subsets differ both in ontogeny and functional properties, such as the capacity to induce CD4+ and CD8+ T-cell activation. MoDCs are most frequently used for vaccination purposes, based on technical aspects such as availability and in vitro expansion. However, whether moDCs are superior over other DC subsets in inducing anti-tumor immune responses, is unknown, and likely depends on tumor type and composition of the tumor microenvironment. In this review, we discuss cellular aspects essential for DC vaccination efficacy, and the most recent findings on different DC subsets that could be used for DC-based cancer immunotherapy. This can prove valuable for the future design of more effective DC vaccines by choosing different DC subsets, and sheds light on the working mechanism of DC immunotherapy

The distress thermometer as a predictor for survival in stage III lung cancer patients treated with chemotherapy

Background: Depression and Health Related Quality of Life have been associated with prognosis in lung cancer. As the Distress Thermometer measures emotional problems and may share similarities with aspects of Health Related Quality of Life, we aimed to retrospectively assess the prognostic value of the Distress Thermometer in lung cancer patients treated with chemotherapy. Methods: Patients with stage III lung cancer who were treated at the day-care oncology unit with chemotherapy containing carboplatin from 2009 to 2014 and in whom a Distress Thermometer was performed at the time of the first cycle of chemotherapy were included in this study. Results: In total, one hundred and thirteen patients were included in the analysis. In the simple Cox regression analysis, overall survival did not significantly differ according to Distress Thermometer score. No significant differences in Distress Thermometer score according to stage, histology, (intended) treatment, age, sex, and comorbidity were observed. Also in a multivariable model the Distress Thermometer was not prognostic for overall survival, whereas sex and (intended) treatment was. Conclusions: In this study no prognostic value of the Distress Thermometer could be established in patients with stage III lung cancer treated with carboplatin. Further research is warranted to address this issue

Combination Strategies to Optimize Efficacy of Dendritic Cell-Based Immunotherapy

Dendritic cells (DCs) are antigen-presenting cells (APCs) that are essential for the activation of immune responses. In various malignancies, these immunostimulatory properties are exploited by DC-therapy, aiming at the induction of effective anti-tumor immunity by vaccination with ex vivo antigen-loaded DCs. Depending on the type of DC-therapy used, long-term clinical efficacy upon DC-therapy remains restricted to a proportion of patients, likely due to lack of immunogenicity of tumor cells, presence of a stromal compartment, and the suppressive tumor microenvironment (TME), thereby leading to the development of resistance. In order to circumvent tumor-induced suppressive mechanisms and unleash the full potential of DC-therapy, considerable efforts have been made to combine DC-therapy with chemotherapy, radiotherapy or with checkpoint inhibitors. These combination strategies could enhance tumor immunogenicity, stimulate endogenous DCs following immunogenic cell death, improve infiltration of cytotoxic T lymphocytes (CTLs) or specifically deplete immunosuppressive cells in the TME, such as regulatory T-cells and myeloid-derived suppressor cells. In this review, different strategies of combining DC-therapy with immunomodulatory treatments will be discussed. These strategies and insights will improve and guide DC-based combination immunotherapies with the aim of further improving patient prognosis and care

Case Report A Patient with Four-Year Survival after Nonsmall Cell Lung Carcinoma with a Solitary Metachronous Small Bowel Metastasis

Solitary small bowel metastasis secondary to lung cancer is very uncommon. In this report, we present a patient with NSCLC and a metachronous solitary metastasis of the jejunum. She is alive without evidence of disease and doing well four years after palliative surgery, radiotherapy, and chemotherapy. To the best of our knowledge, this is the first case report describing a prolonged survival in a patient with a symptomatic solitary small bowel metastasis treated with palliative surgery, chemo-and radiotherapy instead of complete surgical resection

A population-based study describing characteristics, survival and the effect of TKI treatment on patients with EGFR mutated stage IV NSCLC in the Netherlands

INTRODUCTION: Since 2011, treatment guidelines advise targeted therapy (tyrosine kinase inhibitor, TKI) for patients with activating epidermal growth factor receptor (EGFR) mutations (EGFR+) in non-small cell lung cancer (NSCLC). We describe characteristics, first line treatment and survival of patients diagnosed with EGFR+ NSCLC in a European population, focussing on age, gender and trends over time and compare to the whole group and EGFR-. METHODS: All patients with non-squamous NSCLC stage IV, diagnosed 2011-2018, were identified from the population-based Netherlands Cancer Registry (N = 31,291). RESULTS: Among all, 7.0% were registered to be EGFR+, with highest prevalence in females 65 years to 23.6 months in the EGFR+ group <50 years treated with TKI. Over time, OS for the whole group increased by 0.6 months, of which 33% due to TKI treatment in EGFR+. The increase was strongest in females <50 years, where median OS almost doubled to 12.4 months. In the EGFR+, multivariable hazard of death was most strongly associated with the use of TKI (HR 0.45(0.41-0.49)). Of the patients with EGFR+ this space need or not, 71% received TKI treatment. Being young reduced the hazard of death (HR 0.71(95%CI:0.59-0.85)) irrespective of treatment, while male gender increased the hazard of death (HR 1.22(95%CI:1.11-1.33)). CONCLUSION: At population level, TKI treatment in patients with non-squamous NSCLC stage IV EGFR+ has very strong beneficial effects on outcome. Of the improvement in OS that was made over the years for the whole group, about one third seems to be attributed to TKI treatment in EGFR+ patients

Autologous Dendritic Cell Therapy in Mesothelioma Patients Enhances Frequencies of Peripheral CD4 T Cells Expressing HLA-DR, PD-1, or ICOS

Introduction: Malignant pleural mesothelioma (MPM) is a malignancy with a very poor prognosis for which new treatment options are urgently needed. We have previously shown that dendritic cell (DC) immunotherapy provides a clinically feasible treatment option. In the current study, we set out to assess the immunological changes induced by DC immunotherapy in peripheral blood of MPM patients.Methods: Peripheral blood was collected from nine patients enrolled in a phase I dose escalation study, before and after treatment with DCs that were pulsed with an allogeneic tumor lysate preparation consisting of a mixture of five cultured mesothelioma cell lines. We used immune profiling by multiplex flow cytometry to characterize different populations of immune cells. In particular, we determined frequencies of T cell subsets that showed single and combinatorial expression of multiple markers that signify T cell activation, maturation and inhibition. Therapy-induced T cell reactivity was assessed in peptide/MHC multimer stainings using mesothelin as a prototypic target antigen with confirmed expression in the clinical tumor lysate preparation. T cell receptor (TCR) diversity was evaluated by TCRB gene PCR assays.Results: We observed an increase in the numbers of B cells, CD4 and CD8 T cells, but not NK cells at 6 weeks post-treatment. The increases in B and T lymphocytes were not accompanied by major changes in T cell reactivity toward mesothelin nor in TCRB diversity. Notably, we did observe enhanced proportions of CD4 T cells expressing HLA-DR, PD-1 (at 2 weeks after onset of treatment) and ICOS (6 weeks) and a CD8 T cell population expressing LAG3 (2 weeks).Discussion: DC immunotherapy using allogeneic tumor lysate resulted in enhanced frequencies of B cells and T cells in blood. We did not detect a skewed antigen-reactivity of peripheral CD8 T cells. Interestingly, frequencies of CD4 T cells expressing activation markers and PD-1 were increased. These findings indicate a systemic activation of the adaptive immune response and may guide future immune monitoring studies of DC therapies

High familial burden of cancer correlates with improved outcome from immunotherapy in patients with NSCLC independent of somatic DNA damage response gene status

Family history of cancer (FHC) is a hallmark of cancer risk and an independent predictor of outcome, albeit with uncertain biologic foundations. We previously showed that FHC-high patients experienced prolonged overall (OS) and progression-free survival (PFS) following PD-1/PD-L1 checkpoint inhibitors. To validate our findings in patients with NSCLC, we evaluated two multicenter cohorts of patients with metastatic NSCLC receiving either first-line pembrolizumab or chemotherapy. From each cohort, 607 patients were randomly case-control matched accounting for FHC, age, performance status, and disease burden. Compared to FHC-low/negative, FHC-high patients experienced longer OS (HR 0.67 [95% CI 0.46-0.95], p\u2009=\u20090.0281), PFS (HR 0.65 [95% CI 0.48-0.89]; p\u2009=\u20090.0074) and higher disease control rates (DCR, 86.4% vs 67.5%, p\u2009=\u20090.0096), within the pembrolizumab cohort. No significant associations were found between FHC and OS/PFS/DCR within the chemotherapy cohort. We explored the association between FHC and somatic DNA damage response (DDR) gene alterations as underlying mechanism to our findings in a parallel cohort of 118 NSCLC, 16.9% of whom were FHC-high. The prevalence of\u2009 65\u20091 somatic DDR gene mutation was 20% and 24.5% (p\u2009=\u20090.6684) in FHC-high vs. FHC-low/negative, with no differences in tumor mutational burden (6.0 vs. 7.6 Mut/Mb, p\u2009=\u20090.6018) and tumor cell PD-L1 expression. FHC-high status identifies NSCLC patients with improved outcomes from pembrolizumab but not chemotherapy, independent of somatic DDR gene status. Prospective studies evaluating FHC alongside germline genetic testing are warranted