Risk as a pattern over time: Delineation of time-dependent risk factors in biological,psychological, and social variables in cancer patients

Background

Survival in cancer patients is associated with a multitude of biological, social, and psychological factors. Although it is well established that all these factors add to overall mortality, it is not well understood how the predictive power of these parameters changes in a comprehensive model and over time.

Methods

Patients who attended the authors’ outpatient clinic were invited to participate. The authors followed 5180 mixed cancer patients (51.1% female; mean age, 59.1 years [SD = 13.8]) for up to 16 years and analyzed biological (age, sex, cancer site, anemia), psychological (anxiety, depression), and social variables (marital status, education, employment status) potentially predicting overall survival in a Cox proportional hazards model.

Results

The median survival time for the entire sample was 4.3 years (95% confidence interval, 4.0–4.7). The overall survival probabilities for 1 and 10 years were 76.8% and 38.0%, respectively. Following an empirical approach, the authors split the time interval into five periods: acute, subacute, short-term, medium-term, and long-term. A complex pattern of variables predicted overall survival differently in the five periods. Biological parameters were important throughout most of the time, social parameters were either time-independent predictors or tended to be more important in the longer term. Of the psychological parameters, only depression was a significant predictor and lost its predictive power in the long-term.

Conclusions

The findings of this study allow the development of comprehensive patient-specific models of risk and resilience factors addressing biopsychosocial needs of cancer patients, paving the way for a personalized treatment plan that goes beyond biomedical cancer care.     

The role of conventional radiography to assess the outcome of oncologic skeletal reconstructions of lower limbs aided by vascularized fibular autograft

IntroductionVascularized fibular autografts (VFA) are used in the oncologic skeletal reconstructions of long bones, alone or combined with massive bone allografts (MBA). Data regarding the role of imaging in assessing these complex skeletal reconstructions are lacking, and have mainly focused on Computed Tomography (CT). Our aim was to evaluate if early conventional radiography (CR) findings are correlated with the outcome of these skeletal reconstructions.Materials and methodsAll consecutive patients who underwent oncologic resection of lower limbs long bones followed by VFA reconstruction were included in this single-center retrospective study. We compared the CR obtained immediately after surgery with the CR at the 6-month control, as well as the CR at 6 months with the CT at 6 months when available. The following scores were assigned to the VFA: 0 (unchanged), 1 (osteopenia-cortical bone thinning), 2 (increase in bone density-cortical thickening). We then investigated whether this score correlated with the implant outcome within 12 months (optimal integration, suboptimal integration, integration requiring further surgery or lack of integration) using Kaplan-Meier and Cox regression analyses, considering the occurrence of integration and the duration time before the surgical removal of the whole bone reconstruction.ResultsForty-five patients were included (32 men [71.1%], mean age 14.6 years), 26 affected by osteosarcoma, 14 by Ewing sarcoma, 3 by adamantinoma and 2 operated for the failure of previous reconstructions for bone sarcoma. VFA changes on 6-month CR were significantly associated with optimal integration of the implants (log-rank P = 0.0137, multivariate Hazard ratio = 7.62, 95% confidence interval = 1.13–51.25). None of the other clinical and surgical features were associated with the implant outcome. The findings on 6-month CR and CT follow-up were not significantly different. CT at 6 months was available in 36 patients (80.0%).ConclusionThe assessment of VFA morphological changes on CR performed at 6 months can predict the outcome of the skeletal implant. This data should be considered for clinical decision-making, selecting patients requiring additional images (CT), and possible subsequent revision surgical procedures.     

Emerging innovations in cold plasma therapy against cancer: A paradigm shift

Cancer is one of the major causes of mortality, accounting for ～ 9.5 million deaths globally in 2018. The spectrum of conventional treatment for cancer includes surgery, chemotherapy and radiotherapy. Recently, cold plasma therapy surfaced as a novel technique in the treatment of cancer. The FDA approval of the first trial for the use of cold atmospheric plasma (CAP) in cancer therapy in 2019 is evidence of this. This review highlights the mechanisms of action of CAP. Additionally, its applications in anticancer therapy have been reviewed. In summary, this article will introduce the readers to the exciting field of plasma oncology and help them understand the current status and prospects of plasma oncology.     

Role of surgical treatments in high-grade or advanced gastroenteropancreatic neuroendocrine neoplasms

Over the last 40 years, the incidence and prevalence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) have continued to increase. Compared to other epithelial neoplasms in the same organ, GEP-NENs exhibit indolent biological behavior, resulting in more chances to undergo surgery. However, the role of surgery in high-grade or advanced GEP-NENs is still controversial. Surgery is associated with survival improvement of well-differentiated high-grade GEP-NENs, whereas poorly differentiated GEP-NENs that may benefit from resection require careful selection based on Ki67 and other tissue biomarkers. Additionally, surgery also plays an important role in locally advanced and metastatic disease. For locally advanced GEP-NENs, isolated major vascular involvement is no longer an absolute contraindication. In the setting of metastatic GEP-NENs, radical intended surgery is recommended for patients with low-grade and resectable metastases. For unresectable metastatic disease, a variety of surgical approaches, including cytoreduction of liver metastasis, liver transplantation, and surgery after neoadjuvant treatment, show survival benefits. Primary tumor resection in GEP-NENs with unresectable metastatic disease is associated with symptom control, prolonged survival, and improved sensitivity toward systemic therapies. Although there is no established neoadjuvant or adjuvant strategy, increasing attention has been given to this emerging research area. Some studies have reported that neoadjuvant therapy effectively reduces tumor burden, improves the effectiveness of subsequent surgery, and decreases surgical complications.     

Differences in Evidentiary Requirements Between European Medicines Agency and European Health Technology Assessment of Oncology Drugs—Can Alignment Be Enhanced?

ObjectivesNational health technology assessments (HTAs) across Europe show differences in evidentiary requirements from assessments by the European Medicines Agency (EMA), affecting time to patient access for drugs after marketing authorization. This article analyzes the differences between EMA and HTA bodies’ evidentiary requirements for oncology drugs and provides recommendations on potential further alignment to minimize and optimally manage the remaining differences.MethodsInterviews were performed with representatives and drug assessment experts from EMA and HTA bodies to identify evidentiary requirements for several subdomains and collect recommendations for potentially more efficiently addressing differences. A comparative analysis of acceptability of the evidence by EMA and the HTA bodies and for potential further alignment between both authorities was conducted.ResultsAcceptability of available evidence was higher for EMA than HTA bodies. HTA bodies and EMA were aligned on evidentiary requirements in most cases. The subdomains showing notable differences concerned the acceptance of limitation of the target population and extrapolation of target populations, progression-free survival and (other) surrogate endpoints as outcomes, cross-over designs, short trial duration, and clinical relevance of the effect size. Recommendations for reducing or optimally managing differences included joint early dialogues, joint relative effectiveness assessments, and the use of managed entry agreements.ConclusionsDifferences between assessments of EMA and HTA bodies were identified in important areas of evidentiary requirements. Increased alignment between EMA and HTA bodies is suggested and recommendations for realization are discussed.     

Second primary malignancies after ovarian cancer: A SEER-based analysis (1975–2016)

ObjectiveTo investigate the risk of occurrence of second primary malignancies (SPMs) in survivors of ovarian cancer (OC) using large data from the Surveillance, Epidemiology, and End Results (SEER) database.Materials and methodsMultiple primaries standardized incidence ratios (MP-SIRs) to calculate the risk of developing second primary malignancies after a diagnosis of ovarian cancer.ResultsOf our included 59,880 women with OC, 3972 cases (6.6%) developed 4495 s primary malignancies over an average follow-up period of 114.39 (±102.66) months. Overall, the risk of occurrence of second primary malignancies after a diagnosis of OC was greater than what would be expected for a reference US population (SIR = 1.05, 95%CI = 1.02–1.08, p-value < 0.05). The occurrence of second myeloid malignancies and second thyroid cancer were most notable across our latency periods. Among the most significant second primary malignancies by latency were malignancies of the appendix (SIR = 14.04, 95%CI = 5.65–28.93, p-value <0.05) at 2–11 months, the small intestine (SIR = 3.15, 95%CI = 1.76–5.2, p-value <0.05) at 12–59 months, and the urinary bladder (SIR = 1.63, 95%CI = 1.3–2.02, p-value <0.05) after 10 years of an OC diagnosis.ConclusionWomen with OC are at significant risk for the development of second primary malignancies across all sites, as compared to a reference US population, and may benefit from second primary malignancies site-specific screening post-diagnosis.