Systemic Therapy Decision Making in Advanced Cancer: A Qualitative Analysis of Patient-Oncologist Encounters

PURPOSE: We sought to characterize patient-oncologist communication and decision making about continuing or limiting systemic therapy in encounters after an initial consultation, with a particular focus on whether and how oncologists foster shared decision making (SDM). METHODS: We performed content analysis of outpatient oncology encounters at two US National Cancer Institute–designated cancer centers audio recorded between November 2010 and September 2014. A multidisciplinary team used a hybrid approach of inductive and deductive coding and theme development. We used a combination of random and purposive sampling. We restricted quantitative frequency counts to the coded random sample but included all sampled encounters in qualitative thematic analysis. RESULTS: Among 31 randomly sampled dyads with three encounters each, systemic therapy decision making was discussed in 90% (84 of 93) encounters. Thirty-four (37%) broached limiting therapy, which 27 (79%) framed as temporary, nine (26%) as completion of a standard regimen, and five (15%) as permanent discontinuation. Thematic analysis of these 93 encounters, plus five encounters purposively sampled for permanent discontinuation, found that (1) patients and oncologists framed continuing therapy as the default, (2) deficiencies in the SDM process (facilitating choice awareness, discussing options, and incorporating patient preferences) contributed to this default, and (3) oncologists use persuasion rather than deliberation when broaching discontinuation. CONCLUSION: In this study of outpatient encounters between patients with advanced cancer and their oncologists, when discussing systemic therapy, there exists a default to continue systemic therapy, and deficiencies in SDM contribute to this default.

Shifting Gears in Precision Oncology—Challenges and Opportunities of Integrative Data Analysis

For decades, research relating to modification of host immunity towards antitumor response activation has been ongoing, with the breakthrough discovery of immune-checkpoint blockers. Several biomarkers with potential predictive value have been reported in recent studies for these novel therapies. However, with the plethora of therapeutic options existing for a given cancer entity, modern oncology is now being confronted with multifactorial interpretation to devise “the best therapy” for the individual patient. Into the bargain come the multiverse guidelines for established and emerging diagnostic biomarkers, as well as the complex interplay between cancer cells and tumor microenvironment, provoking immense challenges in the therapy decision-making process. Through this review, we present various molecular diagnostic modalities and techniques, such as genomics, immunohistochemistry and quantitative image analysis, which have the potential of becoming powerful tools in the development of an optimal treatment regime when analogized with patient characteristics. We will summarize the underlying complexities of these methods and shed light upon the necessary considerations and requirements for data integration. It is our hope to provide compelling evidence to emphasize on the need for inclusion of integrative data analysis in modern cancer therapy, and thereupon paving a path towards precision medicine and better patient outcomes.

Total Tumor Diameter and Unilateral Multifocality as Independent Predictor Factors for Metastatic Papillary Thyroid Microcarcinoma

The purpose of this study was to assess whether total tumor diameter (TTD) and multifocality are predictors for metastatic disease in papillary thyroid microcarcinomas (PTMC). Eighty-two patients with histologically proven PTMC were retrospectively included. Patients were divided according to the presence of metastatic disease in the metastatic (n = 41) and non-metastatic (n = 41) demographic-matched group. The morphological features of PTMCs (primary tumor diameter, multifocality, TTD, number of foci, and tumor site) were compared between groups using univariate, multivariate, and receiver operating characteristic analyses. TTD (p = 0.026), TTD > 10 mm (p = 0.036), and Unilateral Multifocality (UM) (p = 0.019) statistically differed between the groups. The combination of the two independent predictors (TTD and UM) was able to assess metastatic risk with 60.98% sensitivity and 75.61% specificity. TTD and UM can be used to predict metastatic disease in PTMC, which may help to better adapt the RAI therapy decision. We believe that TTD and multifocality are tumor features that should be considered in future guidelines.

A Typical Perplexing Life-sustaining Therapy Decision at the End of life: A Case Report from Sri Lanka with Attributes Potentially worth Adopting from the UK Legislature

In many developing parts of the world, evidence on advance care planning (ACP) is either lacking or fragmented. Lack of streamlined means for ACP is known to lead to inconveniences for the clinicians as well as the patients and their families. This case report focuses on a young male diagnosed with metastatic osteosarcoma, who explicitly verbalised his wishes to be managed conservatively without involving invasive life-sustaining measures. However, the patient faced cardiopulmonary resuscitation before his demise against his wishes, which also contradicted with the medical point of view. Sri Lankan doctors face moral, ethical and legal dilemmas as they deal with terminally ill patients at the verge of their death due to the deficiencies in the medical and legislative frameworks in the country.

Systematic Analysis Identifies a Specific RNA-Binding Protein-Related Gene Model for Prognostication and Risk-Adjustment in HBV-Related Hepatocellular Carcinoma

ObjectiveIncreasing evidence shows that dysregulated RNA binding proteins (RBPs) modulate the progression of several malignancies. Nevertheless, their clinical implications of RBPs in HBV-related hepatocellular carcinoma (HCC) remain largely undefined. Here, this study systematically analyzed the associations of RBPs with HBV-related HCC prognosis.MethodsBased on differentially expressed RBPs between HBV-related HCC and control specimens, prognosis-related RBPs were screened by univariate analyses. A LASSO model was then created. Kaplan-Meier curves, ROCs, multivariate analyses, subgroup analyses and external verification were separately applied to assess the efficacy of this model in predicting prognosis and recurrence of patients. A nomogram was created by incorporating the model and clinical indicators, which was verified by ROCs, calibration curves and decision curve analyses. By CIBERSORT algorithm, the association between the risk score and immune cell infiltrations was evaluated.ResultsTotally, 54 RBPs were distinctly correlated to prognosis of HBV-related HCC. An 11-RBP model was created, containing POLR2L, MRPS12, DYNLL1, ZFP36, PPIH, RARS, SRP14, DDX41, EIF2B4, and NOL12. This risk score sensitively and accurately predicted one-, three- and five-year overall survival, disease-free survival, and progression-free interval. Compared to other clinical parameters, this risk score had the best predictive efficacy. Also, the clinical generalizability of the model was externally verified in the GSE14520 dataset. The nomogram may predict patients’ survival probabilities. Also, the risk score was related to the components in the immune microenvironment.ConclusionCollectively, RBPs may act as critical elements in the malignant progression of HBV-related HCC and possess potential implications on prognostication and therapy decision.

Proinflammatory and Hepatic Features Related to Morbidity and Fatal Outcomes in COVID-19 Patients

Objective: to screen putative associations between liver markers and proinflammatory-related features concerning infectious morbidity and fatal outcomes in COVID-19 patients. Methods: a total of 2094 COVID-19 positive patients from the COVID-DATA-SAFE-LIFES cohort (HM hospitals consortium) were classified according to median values of hepatic, inflammatory, and clinical indicators. Logistic regression models were fitted and ROC cures were generated to explain disease severity and mortality. Results: intensive care unit (ICU) assistance plus death outcomes were associated with liver dysfunction, hyperinflammation, respiratory insufficiency, and higher associated comorbidities. Four models including age, sex, neutrophils, D-dimer, oxygen saturation lower than 92%, C-reactive protein (CRP), Charlson Comorbidity Index (CCI), FIB-4 and interactions with CRP, neutrophils, and CCI explained ICU plus death variance in more than 28%. The predictive values of ROC curves were: FIB-4 (0.7339), AST/ALT ratio (0.7107), CRP (0.7003), CCI index (0.6778), neutrophils (0.6772), and platelets (0.5618) concerning ICU plus death outcomes. Conclusions: the results of this research revealed that liver and proinflammatory features are important determinants of COVID-19 morbidity and fatal outcomes, which could improve the current understanding of the COVID-19 physiopathology as well as to facilitate the clinical management and therapy decision-making of this disease under a personalized medicine scope.

Identification and Validation of a Four-Long Non-coding RNA Signature Associated With Immune Infiltration and Prognosis in Colon Cancer

The emerging evidence has demonstrated the critical roles of long non-coding RNAs (lncRNAs) as regulators in the tumor immune microenvironment (TIME). However, the tumor immune infiltration-associated lncRNAs and their clinical significance in colon cancer have not yet been thoroughly investigated. This study performed an integrative analysis of lncRNA expression profiles and immune cell infiltration profiles and identified 258 immune infiltration-associated lncRNAs. Of them, four lncRNAs (AC008494.3, LINC00926, AC022034.1, and SNHG26) were significantly and independently associated with the patient’s overall survival. Finally, we developed a tumor immune infiltration-associated lncRNA signature (TIILncSig) comprising of these four lncRNAs, which can divide colon cancer patients of The Cancer Genome Atlas (TCGA) into high-risk and low-risk groups with a significantly different outcome [Hazard ratio (HR) = 2.718, 95% CI = 1.955–3.779, p < 0.001]. Prognostic performance of the TIILncSig was further validated in another independent colon cancer cohort (HR = 1.832, 95% CI = 1.045–3.21, p = 0.034). Results of multivariate Cox regression and stratification analysis demonstrated that the TIILncSig is an independent predictive factor from other clinical features (HR = 2.687, 95% CI = 1.912–3.776, p < 0.001 for TCGA cohort and HR = 1.837, 95% CI = 1.047–3.223, p = 0.034 for GSE17538 cohort). Literature analysis provided experimental evidence supporting roles of the TIILncSig in cancer carcinogenesis and progression and immune regulation. Summary, our study will help to understand the mechanisms of lncRNAs in immune regulation in the tumor microenvironment and provide novel biomarkers or targets for prognosis prediction and therapy decision-making for patients with colon cancer.

How do specialist surgeons treat the atrophic tooth gap? A vignette-based study among maxillofacial and oral surgeons

Background There is little information available regarding the decision-making process of clinicians, especially in the choice of therapy for a severely atrophic tooth gap. The aim of this research was to use case vignettes to determine the influence of possible factors on the decision making of maxillofacial and oral surgeons. Methods A total of 250 maxillofacial (MFS) and oral (OS) surgeons in southern Germany were surveyed for atrophic single- or multiple-tooth gap with the help of case vignettes. The influence of different determinants on the therapy decision was investigated. Two case vignettes were designed for this purpose: vignette 1 with determinants “patient age” and “endocarditis prophylaxis” and vignette 2 with determinants “anxiety” and “bisphosphonate therapy”. Furthermore, the specialist designation was assessed for both. The options available to achieve a sufficient implant site were "bone split", "bone block", "augmentation with bone substitute material" and "bone resection". Therapy was either recommended or rejected based on principle. Results A total of 117 participants returned the questionnaire: 68 (58%) were OS and 49 (42%) MFS. “Patient age” and “patient anxiety” were not significantly associated with any therapy decision. However, required “endocarditis prophylaxis” led to significantly higher refusal rates for "bone split", "bone block" and "bone replacement material" and to higher rates of general refusal of a therapy. “Bisphosphonate therapy” was significantly associated with general refusal of therapy, but with no significant correlation with different therapy options. In vignette 1, OS refused therapy significantly more often than MFS, though there was no association with the specialist designation for other therapy modalities. In vignette 2, specialty was not significantly associated with the therapy decision. Conclusion “Patient age” as well as “patient anxiety” appear to have no or little influence on the treatment decision for severely atrophic single- or multiple-tooth gap by specialist surgeons. Surgeons more often refuse treatment for patients with endocarditis prophylaxis and bisphosphonate therapy.