Comparison of the effectiveness of integrative immunomodulatory treatments and conventional therapies on the survival of selected gastrointestinal cancer patients.

In the last decade, the use of immunomodulating treatments (IMT) at integrative oncology providers (IOP) increased. IMTs are used to modulate the tumor microenvironment, which might lead to increased response-to-treatment, and the indication of immune checkpoint inhibitors might also be widened. The efficacy and safety of IMTs in advanced/metastatic gastrointestinal cancers were compared with conventional chemo(radio)therapy (CT). 21 colorectal- (CRC), 14 pancreatic- (PC), 5 cholangiocellular- (CCC), 5 gastric- (GC) and 4 esophageal cancer (EC) patients received IMT. IMT and CT were compared in CRC and PC. CT was administered at an academic oncology center. After the initiation of IMT, a median survival of ~ 20 (CRC, PC and EC) and ~ 10 months (CCC and GC) was observed. Of the IMTs, locoregional modulated electro-hyperthermia had the most positive effect on overall survival (HR: 0.3055; P = 0.0260), while fever-inducing interleukin-2, and low-dose ipilimumab showed a positive tendency. IMT was superior to CT in PC (HR: 0.1974; P = 0.0013), while modest effect was detected in CRC (HR: 0.7797; P = 0.4710). When the whole study population was analyzed, IMTs showed minimal effect on patient survival, still CT had the greatest effect if introduced as early as possible (HR: 0.0624; P < 0.0001). The integrative IMTs in the presented form have mild impact on gastrointestinal cancer patients' survival, however, we observed its benefit in PC, which warrants further investigations.

Prognostic factors and mitotane treatment of adrenocortical cancer. Two decades of experience from an institutional case series.

Objectives: This study aimed to characterise the clinicopathological features and prognostic factors of a large cohort of Hungarian patients with adrenocortical cancer diagnosed between 2000-2021. Patients and methods: This retrospective study included seventy-four patients (27 men and 47 women) with histologically confirmed adrenocortical cancer in a single tertiary referral endocrine centre. Descriptive statistics were performed, providing summaries of selected clinical and pathological parameters. Clinicopathological factors contributing to overall survival were analysed. Results: The median age of patients was 48,5 years (17-84 years) at diagnosis. The majority of cases were diagnosed at ENSAT stage II (39,2%) and stage IV (33,8%). At diagnosis, the median tumour size was 9,0 cm (4,5-20 cm). In 47 patients (71,6%), the tumour was hormonally active. The median overall survival and the 5-year survival rate were 23,5 months (95% CI, 17-30,5 months) and 18,3%, respectively. Primary tumour resection was performed in 68 patients (91,8%); R0 surgical resection was achieved in 30 patients. In univariate Cox regression model, tumours with stages III and IV, high proliferative activity (Ki67-index > 10%), R1-R2 surgical resection state and hormonal activity were associated with poorer survival. Cortisol excess, both isolated and combined with androgen production, was associated with poorer survival. Fifty-five patients were treated with mitotane. The overall survival of patients achieving therapeutic mitotane plasma concentration was significantly better compared to those who never reached it [27.0 (2-175) months vs 18.0 (2-83) months; p<0.05)]. The median age, the distribution of gender, ENSAT stage, resection state and Ki67-index did not differ between these two groups. The time needed to reach the therapeutic range of serum mitotane was 96.5 days (95% CI, 75-133 days). Conclusion: Our results confirm previous data that disease stage, mitotic activity, the resection state and the mitotane treatment achieving therapeutic concentration are the most critical parameters influencing the prognosis of adrenocortical cancer. Our data suggest that hormonal activity may be more frequent than described previously, and it is a strong and independent prognostic factor of overall survival. To our knowledge, this is the first single-centre study confirming the prognostic importance of achieving therapeutic mitotane concentration.

Longitudinal changes in personalized platelet count metrics are good indicators of initial 3-year outcome in colorectal cancer.

BACKGROUND: Platelet count or complete blood count (CBC)-based ratios including lymphocyte-to-monocyte (LMR), neutrophil-to-lymphocyte (NLR), hemoglobin-to-platelet (HPR), red blood cell count distribution width-to-platelet (RPR), and platelet-to-lymphocyte (PLR) ratio are good predictors of colorectal cancer (CRC) survival. Their change in time is not well documented, however. AIM: To investigate the effect of longitudinal CBC ratio changes on CRC survival and their possible associations with clinicopathological properties, comorbidities, and anamnestic data. METHODS: A retrospective longitudinal observational study was conducted with the inclusion of 835 CRC patients, who attended at Semmelweis University, Budapest. CBC ratios and two additional newly defined personalized platelet count metrics (pPLTD and pPLTS, the platelet counts relative to the measurement at the time of CRC diagnosis and to the one 4-6 wk after tumor removal surgery, respectively) were recorded. RESULTS: The 835 CRC patients had a total of 4608 measurements (5.52 visits/patient, in average). Longitudinal survival models revealed that the increases/decreases in LMR [hazard ratio (HR): 0.4989, P < 0.0001], NLR (HR: 1.0819, P < 0.0001), HPR (HR: 0.0533, P = 0.0038), pPLTD (HR: 4.9229, P < 0.0001), and pPLTS (HR: 4.7568, P < 0.0001) values were poor prognostic signs of disease-specific survival. The same was obtained for all-cause mortality. Most abnormal changes occurred within the first 3 years after the diagnosis of CRC. RPR and PLR had an only marginal effect on disease-specific (P = 0.0675) and all-cause mortality (Bayesian 95% credible interval: 0.90-186.05), respectively. CONCLUSION: LMR, NLR, and HPR are good metrics to follow the prognosis of the disease. pPLTD and pPLTS perform just as well as the former, while the use of RPR and PLR with the course of the disease is not recommended. Early detection of the abnormal changes in pPLTD, pPLTS, LMR, NLR, or HPR may alert the practicing oncologist for further therapy decisions in a timely manner.

Personalized Indicator Thrombocytosis Shows Connection to Staging and Indicates Shorter Survival in Colorectal Cancer Patients with or without Type 2 Diabetes.

BACKGROUND: Pre- and postoperative thrombocytosis was reported to have significant effect on patient survival. However, the definition of thrombocytosis throughout the literature is not unified. METHODS: A retrospective longitudinal observational study has been conducted with the inclusion of 150 colorectal cancer (CRC) patients and 100 control subjects. A new measure of platelet changes at an individual level, named personalized indicator thrombocytosis (PIT) was defined, including 4 anemia adjusted variants. RESULTS: In concordance with the literature, PIT values of control subjects showed a slow decrease in platelet counts, while PIT values of CRC patients were significantly higher (p < 0.0001). More advanced staging (p < 0.0001) and both local (p ≤ 0.0094) and distant (p ≤ 0.0440) metastasis are associated with higher PIT values. Higher PIT values suggested shorter survival times (p < 0.0001). Compared to conventional, a PIT-based definition resulted in approximately 3-times more patients with thrombocytosis. 28% and 77% of the deceased patients had conventional- and PIT-based thrombocytosis, respectively. CONCLUSIONS: Compared to conventional thrombocytosis, as an individual metric, PIT values may indicate the condition of patients more precisely. Possible future applications of PIT may include its usage in therapy decision and early cancer detection; therefore, further investigations are recommended.

[Survival impact of diabetes and paraneoplastic thrombocytosis in women with breast cancer]. / A cukorbetegség és a daganatos thrombocytosis túlélésre gyakorolt hatásának vizsgálata emlotumoros nokben.

Introduction: Thrombocytosis and type 2 diabetes have negative effect on the survival of tumor patients. Previously, their joint effect has not been studied in breast cancer. Aim: The aim of our retrospective study was to investigate the occurrence and effects of thrombocytosis and/or type 2 diabetes in breast cancer patients who attended the 2nd Department of Internal Medicine or the 1st Department of Surgery, Semmelweis University, between 2014 and 2017. Laboratory and anamnestic data were compared at the time of tumor diagnosis between diabetic and non-diabetic groups. Survival analysis was performed to study the effects of thrombocytosis and/or type 2 diabetes. Method: 274 study participants were followed until 31 December 2018, or until their last appearance at the University, or until their death. Results: 5% of the patients had elevated platelet counts (over 400 G/L), and 52 were diabetics. Diabetics were significantly older (non-diabetics: 56.8 ± 13.8 years, diabetics: 67.8 ± 11.0 years, p<0.0001). Triple negative subtype (p = 0.0366), and T1 stage (50%) were present more often in non-diabetics. Stage T2 was more common in diabetic patients (51.9%). Type 2 diabetes was associated with a shorter survival time (p = 0.0032). Thrombocytosis did not affect patient survival. Conclusion: At the diagnosis of breast cancer, existing type 2 diabetes is associated with a more severe clinicopathological stage and shorter survival. We recommend that during routine diabetes controls, women should be made aware of the importance of mammography screening. Moreover, diabetes should be considered as a risk factor; after 30 years of age, diabetics should be screened at least every two years. Orv Hetil. 2019; 160(51): 2012-2020.