Traditional and new markers of infection in adult cancer patients and the possible interfering effect of underlying malignancy on these markers

Abstract The purpose of the present study was to compare the procalcitonin (PCT), neopterin, interleukin-8 (IL-8), interleukin-10 (IL-10) and interleukin-12 (IL-12) levels with those of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in cancer patients with (56) and without infection (36) and to evaluate their ability to differentiate infections from neoplastic fever (n = 10). The infection group had statistically higher levels of CRP (91 vs. 19 mg/l, p < 0.001), PCT (0.28 vs.0.12 ng/ml, p < 0.001), neopterin (12.8 pg/mL vs. 4.0 pg/mL, p < 0.001), IL-8 (27.7 vs. 16.9 pg/ml, p = 0.032), IL-10 (3.8 pg/mL vs. 1.8 pg/mL, p = 0.005) and ratios of neopterin to IL-12 (1.74 vs. 0.11, p < 0.001), and IL-10 to IL-12 (0.4 vs. 0.05, p < 0.001) than the non-infection group. After a subdivision of the study population into patients with local or advanced disease, the differences between the study groups remained statistically significant for CRP and neopterin both in local (p < 0.05 and p < 0.001) and advanced diasease (p < 0.01 and p < 0.001) and in advanced disease for PCT (p < 0.001), IL-10 (p < 0.05), IL-12 (p < 0.05), neopterin to IL-12 ratio (p < 0.01) and IL-10 to IL-12 ratio (p < 0.01). The ESR levels did not differ between the study group (50 vs. 42 p = 0.16), while the IL-12 values were lower in the infection group (10.6 pg/mL vs. 71.6 pg/mL, p = 0.007). The tumor load did not influence any of the studied infection markers within the study groups. For identifying bacteremia by area under the operating characteristics curves (AUC), the highest values were obtained for PCT (0.92) and neopterin (0.90), and slightly lower values were recorded for the ratios neopterin to IL-12 (0.79) and IL-10 to IL-12 (0.75). None of the markers or ratios were good for differentiating non-bacteremic infections from neoplastic fever, the AUC values rangin from 0.27 for ESR to 0.61 for IL-10 to IL-12 ratio. The simultaneous use of the ratio of neopterin to IL-12 with its high sensitivity (82%) and that of IL-10 to IL-12 with its high specificity (90%) should be further studied

Ruokatorvisyövän hoito kehittyy

Tiivistelmä Ruokatorvisyöpä on edelleen tappava tauti, ja vain joka kuudes potilas elää viiden vuoden kuluttua diagnoosin saamisesta. Taudin tyyppi ja levinneisyys selvitetään endoskopialla, biopsioilla ja kuvantamistutkimuksilla. Pinnallisen ruokatorvisyövän ensisijainen hoito on endoskooppinen limakalvoresektio tai endoskooppinen submukoosadissektio. Paikallinen, endoskooppiseen hoitoon soveltumaton syöpä leikataan. Suositeltava ruokatorvisyövän radikaalileikkaus on mini-invasiivinen esofagektomia. Paikallisesti edennyt syöpä hoidetaan yhdistämällä onkologinen ja leikkaushoito. Definitiivisellä kemosädehoidolla hoidetaan leikkaukseen soveltumattomat syövät. Leikatuista potilaista yli 40 % elää yli viisi vuotta. Jos tauti on levinnyt, elinajan odote on alle vuoden. Ravitsemuksesta huolehtiminen sekä kivun ja nielemisvaikeuksien hoito on keskeistä taudin kaikissa vaiheissa.Abstract Esophageal cancer continues to be a cancer of high mortality, the 5-year survival being 14 to 17%. The histological type and staging is based on endoscopy, biopsies and radiology. The first-line treatments of superficial cancers are endoscopic mucosal resection and endoscopic submucosal dissection. Local cancer that cannot be treated with endoscopy is treated operatively. Minimally invasive esophagectomy is the recommended type of radical surgery for esophageal cancer. Adjuvant therapy combined with esophagectomy is the mainstay of locally advanced cancer. Definitive chemoradiotherapy is mostly used in patients not suitable for surgery. The 5-year survival of operated esophageal cancer is over 40%. In advanced cancers, the prognosis is less than a year. Treating dysphagia, pain and nutrition is important in all stages of the disease

Assessment of chemotherapy-induced neurotoxicity using a point-of-care nerve conduction study device

Abstract Background: Management for chemotherapy-induced peripheral neuropathy (CIPN) includes prompt recognition and dose reduction or discontinuation of the neurotoxic agents. CIPN remains under-detected in routine clinical practice and better methods for its early detection are warranted. Aims: To evaluate the feasibility of a point-of-care device in the early detection of CIPN. Methods and Results: Cancer patients (n = 12) scheduled to receive neurotoxic chemotherapy docetaxel, oxaliplatin (OX), or vincristine were recruited for the pilot study (NCT04778878). The patients were assessed with a point-of-care nerve conduction study device (Mediracer® NCS), EORTC QLQ-CIPN20 and NPSI questionnaires, and healthcare professional-assessed CTCAE-based grading at baseline and thereafter every 6-weeks up to 18 weeks or until chemotherapy discontinuation. The set-up of point-of-care device was easy but it only provide successful NCS measurement results in 55% of the patients. The factors related to failed measurement were older age, more frequent comorbidities, and a history of smoking. With the follow-up measurements, decreasing median nerve mean conduction velocity and amplitude, and increasing median nerve mean distal latency were detected on OX-patients. Of the used questionnaires, NPSI was found to be non-feasible with majority of the patients failing to complete the questionnaire while CIPN20 was feasible on all the subjects. CIPN20 score did not show any changes in the follow-up. Conclusions: Point-of-care assessment for NCS was feasible but measurements frequently failed especially on patients with pre-existing high-risk for neuropathy. OX-treated showed decreasing NCS results while other measures were unable to access the change. The system should be further validated with a larger patient cohort preferably treated with OX and low-risk for pre-existing neuropathy

Quality of life with biweekly docetaxel and capecitabine in advanced gastro-oesophageal cancer

Abstract Purpose: This study aimed to evaluate the feasibility and tolerability of biweekly docetaxel with capecitabine as first-line treatment in advanced gastro-oesophageal cancer. Methods: Fifty-three patients at median age of 61 years with advanced gastric cancer were included in this prospective, non-randomized, multicentre phase II trial to receive intravenous docetaxel 50 mg/m² on days 1 and 15, and oral capecitabine 1250 mg/m² every 12 h, on days 1–7 and 15–21 of each 28-day cycle. QOL was assessed using EORTC QLQ-C30, together with the gastric module (QLQ-STO 22). Results: Forty-six patients were evaluable for QOL analyses. No deterioration in global health status was found. Social functioning scores improved, and eating difficulties and pain were alleviated during treatment. The most common grade 3 or 4 toxicity was neutropenia (47%), whereas neutropenic fever was uncommon (6%). The clinical benefit rate was 60%, including complete and partial responses as well as stabilized disease. Median overall survival was 8.8 months (95% CI 5.8–11.9 months), and median time to progression was 6.2 months (95% CI 4.9–7.5 months). Conclusions: Biweekly docetaxel with capecitabine is a feasible treatment in AGC, delivered on an outpatient basis, with no need for central venous access device. No deterioration of global health status was reported. In addition, pain and eating difficulties were alleviated during study treatment. This trial is registered at ClinicalTrials.gov, number NCT00669370

Association of insulin and cholesterol levels with peripheral nervous system function in overweight adults:a 3-year follow-up

Abstract Purpose: The purpose of this prospective 3-year follow-up was to investigate the association of glucose, insulin, and cholesterol levels with peripheral nervous system function in overweight and obese subjects. Methods: Forty nondiabetic overweight and obese adults were enrolled, of whom 29 completed the follow-up. Peripheral nervous system function was measured and defined by conduction studies of the peroneal motor nerve and the radial, sural, and medial plantar sensory nerves. Serum insulin and glucose levels were determined with an oral glucose tolerance test, and cholesterol levels were measured. The measurements were performed at baseline and after 3 years. Results: The change in serum insulin level at 120 minutes after an oral glucose tolerance test was positively associated with changes in peroneal nerve conduction velocities and F-wave mean, sural nerve conduction and medial plantar nerve conduction velocities. Action potential amplitudes decreased consistently and significantly in all sensory nerves. Conclusions: The change in serum insulin level at 120 minutes appears to be positively associated with changes in nerve conduction velocities more than 3 years but not with nerve action potential amplitudes. Significant decreases in the action potential amplitudes of all sensory nerves suggest that such changes might be the earliest detectable sign of damage to the peripheral nervous system in overweight and obese people without type 2 diabetes

Oral sea buckthorn oil attenuates tear film osmolarity and symptoms in individuals with dry eye

v2010o

KRAS-G12C mutation in one real-life and three population-based Nordic cohorts of metastatic colorectal cancer

Abstract Background: KRAS mutations, present in over 40% of metastatic colorectal cancer (mCRC), are negative predictive factors for anti-EGFR therapy. Mutations in KRAS-G12C have a cysteine residue for which drugs have been developed. Published data on this specific mutation are conflicting; thus, we studied the frequency and clinical characteristics in a real-world and population-based setting. Methods: Patients from three Nordic population-based cohorts and the real-life RAXO-study were combined. RAS and BRAF tests were performed in routine healthcare, except for one cohort. The dataset consisted of 2,559 patients, of which 1,871 could be accurately classified as KRAS, NRAS, and BRAF-V600E. Demographics, treatments, and outcomes were compared using logistic regression. Overall survival (OS) was estimated with Kaplan–Meier, and differences were compared using Cox regression, adjusted for baseline factors. Results: The KRAS-G12C frequency was 2%–4% of all tested in the seven cohorts (mean 3%) and 4%–8% of KRAS mutated tumors in the cohorts (mean 7%). Metastasectomies and ablations were performed more often (38% vs. 28%, p = 0.040), and bevacizumab was added more often (any line 74% vs. 59%, p = 0.007) for patients with KRAS-G12C- vs. other KRAS-mutated tumors, whereas chemotherapy was given to similar proportions. OS did not differ according to KRAS mutation, neither overall (adjusted hazard ratio (HR) 1.03; 95% CI 0.74–1.42, reference KRAS-G12C) nor within treatment groups defined as “systemic chemotherapy, alone or with biologics”, “metastasectomy and/or ablations”, or “best supportive care”, RAS and BRAF wild-type tumors (n = 548) differed similarly to KRAS-G12C, as to other KRAS- or NRAS-mutated (n = 66) tumors. Conclusions: In these real-life and population-based cohorts, there were no significant differences in patient characteristics and outcomes between patients with KRAS-G12C tumors and those with other KRAS mutations. This contrasts with the results of most previous studies claiming differences in many aspects, often with worse outcomes for those with a KRAS-G12C mutation, although not consistent. When specific drugs are developed, as for this mutation, differences in outcome will hopefully emerge

Health-related quality of life in metastatic colorectal cancer patients treated with curative resection and/or local ablative therapy or systemic therapy in the Finnish RAXO-study

Abstract Metastasectomy and/or local ablative therapy in metastatic colorectal cancer (mCRC) patients often provide long-term survival. Health-related quality of life (HRQoL) data in curatively treated mCRC are limited. In the RAXO-study that evaluated repeated resectability, a multi-cross-sectional HRQoL substudy with 15D, EQ-5D-3L, QLQ-C30, and QLQ-CR29 questionnaires was conducted. Mean values of patients in different treatment groups were compared with age- and gender-standardized general Finnish populations. The questionnaire completion rate was 444/477 patients (93%, 1751 questionnaires). Mean HRQoL was 0.89–0.91 with the 15D, 0.85–0.87 with the EQ-5D, 68–80 with the EQ-5D-VAS, and 68–79 for global health status during curative treatment phases, with improvements in the remission phase (disease-free >18 months). In the remission phase, mean EQ-5D and 15D scores were similar to the general population. HRQoL remained stable during first- to later-line treatments, when the aim was no longer cure, and declined notably when tumour-controlling therapy was no longer meaningful. The symptom burden affecting mCRC survivors’ well-being included insomnia, impotence, urinary frequency, and fatigue. Symptom burden was lower after treatment and slightly higher, though stable, through all phases of systemic therapy. HRQoL was high in curative treatment phases, further emphasizing the strategy of metastasectomy in mCRC when clinically meaningful

Resectability, conversion, metastasectomy and outcome according to RAS and BRAF status for metastatic colorectal cancer in the prospective RAXO study

Abstract Background: Outcomes after metastasectomy for metastatic colorectal cancer (mCRC) vary with RAS and BRAF mutational status, but their effects on resectability and conversion rates have not been extensively studied. Methods: This substudy of the prospective RAXO trial included 906 patients recruited between 2011 and 2018. We evaluated repeated centralised resectability assessment, conversion/resection rates and overall survival (OS), according to RAS and BRAF status. Results: Patients included 289 with RAS and BRAF wild-type (RAS and BRAFwt), 529 with RAS mutated (RASmt) and 88 with BRAF mutated (BRAFmt) mCRC. Metastatic prevalence varied between the RAS and BRAFwt/RASmt/BRAFmt groups, for liver (78%/74%/61%), lung (24%/35%/28%) and peritoneal (15%/15%/32%) metastases, respectively. Upfront resectability (32%/29%/15%), conversion (16%/13%/7%) and resection/local ablative therapy (LAT) rates (45%/37%/17%) varied for RASa and BRAFwt/RASmt/BRAFmt, respectively. Median OS for patients treated with resection/LAT (n = 342) was 83/69/30 months, with 5-year OS-rates of 67%/60%/24%, while systemic therapy-only patients (n = 564) had OS of 29/21/15 months with 5-year OS-rates of 11%/6%/2% in RAS and BRAFwt/RASmt/BRAFmt, respectively. Resection/LAT was associated with improved OS in all subgroups. Conclusions: There were significant differences in resectability, conversion and resection/LAT rates according to RAS and BRAF status. OS was also significantly longer for RAS and BRAFwt versus either mutant. Patients only receiving systemic therapy had poorer long-term survival, with variation according to molecular status