Isolated Splenic Metastasis of Primary Lung Cancer Presented as Metachronous Oligometastatic Disease—A Case Report

Modern oncology practice and new antitumor drugs prolonged disease-free intervals in patients with lung cancer. Patients with distant metastatic disease are treated only with palliative intent. The International Association for the Study of Lung Cancer, in the 8th edition of the TNM classification, for the first time includes oligometastatic disease as a clinical state that describes the patients with distant metastasis, limited in number and organ sites, who may have more indolent biology. In this paper, we present a case of a 56-year-old man who was admitted to our clinic regarding a radiologically diagnosed splenic lesion of uncertain nature, and who underwent a left upper lobectomy for primary lung cancer 12 years before. After a detailed radiological diagnosis, it was concluded that it is highly suspected metastatic lesion of the spleen and the patient underwent a splenectomy. While no definitive protocols exist on the management of isolated splenic metastasis from lung cancer, splenectomy, in suitable patients, with reasonable survival expectations, improves patient disease-free survival and can prevent potentially life-threatening complications, such as splenic rupture. 18F-FDG PET has very high sensitivity and specificity for differentiating benign and malignant splenic lesions especially in patients who are in the follow up protocol due to primary malignancy.

Time for an individualized approach to first-line management of follicular lymphoma

Follicular lymphoma is a heterogeneous B-cell lymphoma both in presentation and at progression. For most patients it is a chronic, relapsing indolent disease with overall survival expectations now potentially beyond 20 years. However, in a significant minority (~20%) who experience early progression or histological transformation after treatment, the disease no longer has an indolent behavior. This review looks at the development of prognostic indices, staging and therapies for follicular lymphoma, identifying where the data can, and cannot, guide the multidisciplinary team to determine an individualized approach to first-line therapy. A nuanced patient- and disease-specific approach is necessary to maximize disease response and survival while minimizing therapeutic toxicity.

M6a Regulator-Associated Methylation Modification Patterns Shape Tumor Microenvironment Characteristics in Hepatocellular Carcinoma

Although substantial achievements in the tumor microenvironment (TME) of hepatocellular carcinoma (HCC) have led to fundamental improvements both in the basic research and clinical management, the potential mechanisms and regulatory relationships between m6A regulators and the TME are still unknown. We first conducted unsupervised clustering on the samples according to the core m6A expression, and then compared the signaling pathways, differential genes (DEGs), and TME between the m6A phenotypes, and re-validated the relationship between m6A regulators and TME by single cell sequencing. Then, the geneCluster was obtained by another unsupervised clustering of the DEGs, and the clinical as well as TME traits were evaluated among the geneClusters. Finally, the m6A scores of individual patients were calculated by principal component analysis (PCA) to verify the correlation from multiple perspectives, including survivals, clinical characters, mutations, TME, immunotherapy, and chemotherapy. Through a comprehensive analysis of 729 samples, we classified HCC patients into three m6A clusters and three geneClusters. Each group exhibited remarkable variations in terms of signaling pathways, clinical traits, and survival expectations. Notably, the m6A phenotypes corresponded to three different types of TME, namely immune-inflamed, immune-excluded, and immune-desert, respectively. In addition, the m6A regulator can accurately reflect the individualized microenvironment in HCC, and present supreme expression levels in the stromal microenvironment. However, the m6A score system is able to make accurate predictions not only in terms of clinical traits, survival prediction, and TME mentioned above, but also in the sensitivity of HCC patients to immunotherapy and chemotherapy. This study revealed the uniqueness and pluripotency of m6A regulators in the TME of HCC by combining single-cell sequencing and bulk sequencing. The quantified m6A modification indices were able to accurately predict patient survival expectations, clinical traits, TME, and sensitivity to immunotherapy and chemotherapy.

Accuracy incentives and framing effects to minimize the influence of cognitive bias among advanced cancer patients

Many patients with advanced illness have unrealistic survival expectations, largely due to cognitive biases. Studies suggests that when people are motivated to be accurate, they are less prone to succumb to these biases. Using a randomized survey design, we test whether offering advanced cancer patients ( n = 200) incentives to estimate their prognosis improves accuracy. We also test whether presenting treatment benefits in terms of a loss (mortality) rather than a gain (survival) reduces willingness to take up a hypothetical treatment. Results are not consistent with the proposed hypotheses for either accuracy incentives or framing effects.

CheckMate 8KX: Phase 1/2 multitumor preliminary analyses of a subcutaneous formulation of nivolumab (± rHuPH20).

2575 Background: Immunotherapy has transformed cancer survival expectations. Nivolumab (NIVO), a programmed death-1 inhibitor, is approved for intravenous (IV) administration across multiple cancers. BMS is developing a subcutaneous (SC) NIVO formulation with a permeation enhancer, recombinant human hyaluronidase PH20 enzyme (rHuPH20), to allow for more rapid delivery and the potential to decrease treatment burden. We report the first data on pharmacokinetics (PK), pharmacodynamics, safety, and immunogenicity for SC NIVO + rHuPH20. Methods: CheckMate 8KX is a phase 1/2 study in checkpoint inhibitor-naïve patients (pts) who were ≥ 18 years of age, ECOG PS 0–1, with metastatic/unresectable solid tumors and measurable disease. The primary objective was to describe SC NIVO PK; secondary objectives were safety and immunogenicity. Additional analyses compared exposures to historical IV NIVO (Zhao X, et al. J Clin Oncol 2020;31:302–309). In cycle 1, pts in Part A received SC NIVO 720 mg + rHuPH20, and pts in Part B received SC NIVO 720 mg, SC NIVO 960 mg + rHuPH20, or SC NIVO 960 mg. For cycles 2+, pts in Parts A and B received IV NIVO 480 mg every 4 weeks (Q4W). Pts still on study switched to Part C, SC NIVO 1200 mg + rHuPH20 until end of therapy. In Part D, pts received de novo SC NIVO 1200 mg + rHuPH20 Q4W. Results: Patient characteristics varied by age, weight, tumor type, and prior treatment. NIVO exposures increased with increasing SC dose (Table). For 960 mg and 1200 mg NIVO + rHuPH20, Cavg and Ctau were above geometric mean exposures for IV NIVO 3 mg/kg every 2 weeks (Q2W), and Cmax was below IV NIVO 10 mg/kg Q2W. In Part C (n = 28), 13 (46.4%) pts experienced any-grade TRAEs with no new/worsening grade 3+ TRAEs or TRAEs leading to discontinuation/death; 7 (25.0%) reported grade 1 local site reactions. In Part D (n = 36), 27 (75.0%) pts experienced any-grade TRAEs, 4 (11.1%) grade 3/4 TRAEs, 2 (5.6%) serious grade 3/4 TRAEs with 1 leading to discontinuation, and no treatment-related deaths; 10 (27.8%) reported grade 1 local site reactions. Anti-NIVO antibodies (Ab) were observed with SC NIVO but not associated with altered PK/safety, or neutralizing Ab. Exploratory biomarker data found increased CD8+ tumor-infiltrating lymphocytes and PD-L1 tumor expression in post-treatment biopsies, similar to IV NIVO. Conclusions: Exposures associated with SC NIVO + rHuPH20 doses investigated in CheckMate 8KX were well tolerated, with a safety profile consistent with IV NIVO. Data support evaluation of SC NIVO + rHuPH20 in a phase 3 study. Clinical trial information: NCT03656718. [Table: see text]

Subjective survival expectations and morbidity patterns of European citizens aged 50 years and older

Οι προσδοκίες των ανθρώπων για την μελλοντική επιβίωση τους μεταβάλλονται κατά τη διάρκεια της ζωής τους. Κάποιοι είναι σταθερά πιο αισιόδοξοι και πιστεύουν ότι οι πιθανότητες της μελλοντικής επιβίωσης τους είναι υψηλές. Η συστηματική διερεύνηση των χαρακτηριστικών τόσο των αισιόδοξων όσο και των απαισιόδοξων ανθρώπων μπορεί να αποκαλύψει τους λόγους διαφορών της αναμενόμενης Υποκειμενικής Επιβίωσης.Τα αποτελέσματα αυτής της διατριβής δείχνουν ότι υπάρχουν κοινοί παράγοντες που επηρεάζουν τις Υποκειμενικές Πιθανότητες Επιβίωσης. Αφενός, παράγοντες όπως ένας μεγάλος αριθμός παιδιών, υψηλότερη κοινωνικό-οικονομική κατάσταση, συχνή σωματική δραστηριότητα, συχνή κατανάλωση φρούτων ή λαχανικών και αυγών ή οσπρίων καθώς και καλύτερη ποιότητα ζωής σχετίζονται με υψηλότερες Υποκειμενικές Πιθανότητες Επιβίωσης, νεανική Βιολογική Ηλικία καθώς και μακροζωία. Από την άλλη πλευρά, παράγοντες όπως κακή υγείας, περισσότεροι περιορισμοί στις Δραστηριότητες της καθημερινής ζωής, μεγαλύτερος αριθμός χρόνιων ασθενειών, κακή μνήμη, κακές δεξιότητες γραφής και κατάθλιψη σχετίζονται με χαμηλότερες Υποκειμενικές Πιθανότητες Επιβίωσης, εξελιγμένη Βιολογικής Ηλικίας και υψηλότερη θνησιμότητα.Ένας από τους ερευνητικούς στόχους της παρούσας διατριβής είναι η εξέλιξη μιας καινοτόμου μεθόδου για την εκτίμηση της «Υποκειμενική Ηλικία Επιβίωσης», με βάση τις Υποκειμενικές Πιθανότητες Επιβίωσης και τους πινάκες θνησιμότητας του γενικού πληθυσμού. Τα αποτελέσματα της διατριβής δείχνουν σαφώς ότι τόσο οι Υποκειμενικές Πιθανότητες Επιβίωσης όσο και η «Υποκειμενική Ηλικία Επιβίωσης» είναι ανεξάρτητοι παράγοντες που προβλέπουν θνησιμότητα. Αυτό συνεπάγεται ότι οι δύο ποσότητες αυτές περιλαμβάνουν «πληροφορίες επιβίωσης» σημαντικές για την πρόβλεψη της πραγματικής επιβίωσης και μπορούν να χρησιμοποιηθούν για την εκτίμηση Δεικτών Γήρανσης του πληθυσμού. Τέλος, τα πρότυπα της «Υποκειμενικής Ηλικίας Επιβίωσης» είναι επίσης συγκρίσιμα με τα πρότυπα της Βιολογικής Ηλικίας και της Υποκειμενικής Ηλικίας.Η εισαγωγή της έννοιας «Υποκειμενική Ένταση Θνησιμότητας» επιτρέπει τον επαν-υπολογισμό των Υποκειμενικών Πιθανοτήτων Επιβίωσης για μικρότερο χρονικό ορίζοντα εκτίμησης. Για παράδειγμα οι συμμετέχοντες στο SHARE Wave 6 εκτιμούν την πιθανότητα επιβίωσης τους για τα επόμενα 14 έτη, κατά μέσο όρο. Ωστόσο, για την εκτίμηση της ακρίβειας των Υποκειμενικών Πιθανοτήτων Επιβίωσης μικρότεροι χρονικοί ορίζοντες εκτίμησης απατούνται (π.χ. 2 έτη μέχρι το επόμενο SHARE Wave). Οι Υποκειμενικές Πιθανότητες Επιβίωσης με μικρότερο χρονικό ορίζοντα εκτιμώνται με την χρήση της «Υποκειμενική Ένταση Θνησιμότητας».Τα αποτελέσματα δείχνουν ότι αφενός οι Υποκειμενικές Πιθανότητες Επιβίωσης που αντιστοιχούν σε χρονικό ορίζονται 2 ετών (μέχρι το SHARE Wave 7) και αφετέρου η «Υποκειμενική Ηλικία Επιβίωσης», είναι ανεξάρτητοι παράγοντες που προβλέπουν θνησιμότητα και περιλαμβάνουν πληροφορίες σημαντικές για την πρόβλεψη της πραγματικής επιβίωσης.

Racial Differences in the Impact of Subjective Life Expectancy on Advance Care Planning

The need for advance care planning (ACP) is heightened during the COVID-19 pandemic, especially for older Blacks and Latinx persons who are at a disproportionate risk of death from both infectious and chronic disease. A potentially important yet underexplored explanation for well-documented racial disparities in ACP is subjective life expectancy (SLE), which may impel or impede ACP. Using Health and Retirement Study data (n=7484), we examined the extent to which perceived chances of living another 10 years (100, 51-99, 50, 1-49, or 0 percent) predict three aspects of ACP (living will (LW), durable power of attorney for health care designations (DPAHC), and discussions). We use logistic regression models to predict the odds of each ACP behavior, adjusted for sociodemographic, health, and depressive symptoms. We found modest evidence that SLE predicts ACP behaviors. Persons who are 100% certain they will be alive in ten years are less likely (OR = .68 and .71, respectively) whereas those with pessimistic survival prospects are more likely (OR = 1.23 and 1.15, respectively) to have a LW and a DPAHC, relative to those with modest perceived survival. However, upon closer inspection, these patterns hold only for those whose LW specify aggressive measures versus no LW. We found no race differences for formal aspects of planning (LW, DPAHC) although we did detect differences for informal discussions. Blacks with pessimistic survival expectations are more likely to have discussions, whereas Latinos are less likely relative to whites. We discuss implications for policies and practices to increase ACP rates.

Cohort profile: the mature adults cohort of the Malawi longitudinal study of families and health (MLSFH-MAC)

PurposeThe Mature Adults Cohort of the Malawi Longitudinal Study of Families and Health (MLSFH-MAC) contributes to global ageing studies by providing a rare opportunity to study the processes of individual and population ageing, the public health and social challenges associated with ageing and the coincident shifts in disease burdens, in a low-income, high HIV prevalence, sub-Saharan African (SSA) context.ParticipantsThe MLSFH-MAC is an open population-based cohort study of mature adults aged 45+ years living in rural communities in three districts in Malawi. Enrolment at baseline is 1266 individuals in 2012. Follow-ups were in 2013, 2017 and 2018 when the cohort size reached 1626 participants in 2018.Findings to dateSurvey instruments cover ageing-related topics such as cognitive and mental health, non-communicable diseases (NCDs) and related health literacy, subjective survival expectations, measured biomarkers including HIV, grip strength, hypertension, fasting glucose, body mass index (BMI), broad individual-level and household-level social and economic information, a 2018 qualitative survey of mature adults and community officials, 2019 surveys of village heads, healthcare facilities and healthcare providers in the MLSFH-MAC study areas. Across many domains, MLSFH-MAC allows for comparative research with global ageing studies through harmonised measures and instruments. Key findings to date include a high prevalence of depression and anxiety among older adults, evidence for rapid declines in cognitive health with age, a low incidence of HIV among mature adults, rising prevalence of HIV due to increased survival of HIV-positive individuals and poor physical health with high NCD prevalence.Future plansAn additional wave of MLSFH-MAC is forthcoming in 2021, and future expansions of the cohort are planned. MLSFH-MAC data will also be publicly released and will provide a wealth of information unprecedented for ageing studies in a low-income SSA context that broadly represents the socioeconomic environment of millions of individuals in south-eastern Africa.

Xeloda Oral, Trastuzumab, and Pertuzumab Combined Drug Therapy Reduced Cervical Lymphadenopathy and Dermal Involvement in Patient With Recurrent Breast Cancer: Case Report

We report the case of a 42-year-old woman who was diagnosed with breast cancer that recurred 3 years later, with supraclavicular lymphadenopathy and dermal involvement. The main drug used in the therapy was trastuzumab; however, the association of this drug with docetaxel was not able to decrease or cease the effect of the inflammatory BCA component with erythema and thickening of the skin as well as the supraclavicular lymphadenopathy previously diagnosed. Thus, a combined therapy was required. The patient was started on 6 cycles (1 per month) of trastuzumab subcutaneous 600 mg, pertuzumab intravenous 840 mg (as an attack dose, later on 420 mg), and xeloda oral 1000 mg. As a result, the patient showed a significant improvement in erythema and thickening of the skin in the neck and the right part of her trunk, besides decrease in supraclavicular lymphadenopathy. After 6 cycles, her skin was almost restored. Intravenous trastuzumab can be an effective single agent; however, its association with other chemotherapies—such as pertuzumab—can present a synergic effect, which can increase the survival expectations of metastatic HER2+ patients. Additionally, as reported in the literature, the use of xeloda plays a key role in restoring the skin health of patients with breast cancer presenting with skin metastasis. Our findings suggest that trastuzumab, pertuzumab, and xeloda combined therapy, following the schedule and posology handled in this study, can be a good treatment for recurrent HER2+ breast cancer with signs of supraclavicular lymphadenopathy and severe inflammatory BCA component with erythema and thickening of the skin.