Improving Colon Cancer Prevention in Poland. A Long Way Off.

The aim of this study was to analyse knowledge on colon cancer prevention among patients of primary care and identify their sources of information. The questionnaire study was conducted among patients of 36 primary healthcare clinics in Poland between September 2018 and February 2019. Patients were interviewed separately by trained researchers. Over 39% of the primary health patients declared that their knowledge about colon cancer prevention is unsatisfactory. Information about colon cancer prevention varied according to sex, age and BMI. Men declared lower level of knowledge than women: 46% of men thought it was unsatisfactory compared with 36% of women (p = 0.003). Preventive recommendations were more often provided to patients over 60 years old (p < 0.01). Overweight and obese patients were more likely to receive recommendations on diet (p < 0.001) and physical activity (p < 0.001) than patients with normal weight. The most common source of information on colon cancer prevention was Internet (68%) and medical doctors (60%). There is a need for developing colon cancer prevention policy. Crucial aspect includes educational programs aimed at improving patient's knowledge and involving medical staff. The policymakers should pay greater attention to cancer prevention policies and medical staff involved in prevention to quality of communication to make sure patients thoroughly understand information they are provided.

Hyperthermia in rheumatic diseases. A promising approach?

Hyperthermia is a method applied in the treatment of many diseases, including rheumatic diseases. There are relatively few reports concerning the role of that method in the treatment of these diseases, and most studies have not been randomised. Hyperthermia includes directed application of thermal energy. The aim of that therapy is to overcome the body's natural thermoregulation mechanism through application of external heat sources such as electromagnetic radiation of various frequencies, or ultrasound. Usually, temperatures are used within the 38.5-43° range. Hyperthermia can be applied as topical, regional, or systemic treatment (the latter is called hyperthermia of the whole body). In rheumatology, mainly the effect of hyperthermia on the immune system of the body is used. That effect depends on the type of hyperthermia and temperatures applied. Best documented are the effects of hyperthermia in fibromyalgia and ankylosing spondylitis.

Lost in Communication: Do Family Physicians Provide Patients with Information on Preventing Diet-Related Diseases?

Diet-related diseases remain leading causes of death in most developed countries around the world. The aim of the study was to compare opinions of patients and family physicians on receiving and providing recommendations about physical activity, diet and use of medication. Methods: The questionnaire study was conducted among patients of 36 primary health care clinics in Poland between September 2018 and February 2019. Patients and physicians were interviewed separately by trained researchers. Data from 509 patients and 167 family doctors were analyzed. Results: The median age of patients was 44 years (interquartile range: 29-55) and 70% were women. The majority of physicians were women (59%) and the median age was 37 years (IQR: 31-50). There was a significant difference between physicians' declarations on providing recommendations on diet (92% vs. 39%) and activity (90% vs. 37%) versus patients' declarations on receiving them. Conclusions: The results indicate that there is significant room for improvement in providing patients with proper recommendations on diet and physical activity by their family physicians. Primary care physicians should put more emphasis on clear communication of recommendations on diet and physical activity.

A phase 1, open-label, drug-drug interaction study of rucaparib with rosuvastatin and oral contraceptives in patients with advanced solid tumors.

PURPOSE: This study aimed at evaluating the effect of rucaparib on the pharmacokinetics of rosuvastatin and oral contraceptives in patients with advanced solid tumors and the safety of rucaparib with and without coadministration of rosuvastatin or oral contraceptives. METHODS: Patients received single doses of oral rosuvastatin 20 mg (Arm A) or oral contraceptives ethinylestradiol 30 µg + levonorgestrel 150 µg (Arm B) on days 1 and 19 and continuous doses of rucaparib 600 mg BID from day 5 to 23. Serial blood samples were collected with and without rucaparib for pharmacokinetic analysis. RESULTS: Thirty-six patients (n = 18 each arm) were enrolled and received at least 1 dose of study drug. In the drug-drug interaction analysis (n = 15 each arm), the geometric mean ratio (GMR) of maximum concentration (Cmax) with and without rucaparib was 1.29 for rosuvastatin, 1.09 for ethinylestradiol, and 1.19 for levonorgestrel. GMR of area under the concentration-time curve from time zero to last quantifiable measurement (AUC0-last) was 1.34 for rosuvastatin, 1.43 for ethinylestradiol, and 1.56 for levonorgestrel. There was no increase in frequency of treatment-emergent adverse events (TEAEs) when rucaparib was given with either of the probe drugs. In both arms, most TEAEs were mild in severity and considered unrelated to study treatment. CONCLUSION: Rucaparib 600 mg BID weakly increased the plasma exposure to rosuvastatin or oral contraceptives. Rucaparib safety profile when coadministered with rosuvastatin or oral contraceptives was consistent with that of rucaparib monotherapy. Dose adjustments of rosuvastatin and oral contraceptives are not necessary when coadministered with rucaparib. ClinicalTrials.gov NCT03954366; Date of registration May 17, 2019.

Diagnostic imaging approach to gastro-entero-pancreatic carcinomas of neuroendocrine origin - single NET center experience in Poland.

AIM: The aim of the study was to review the current diagnostic approach, based on the experience of one center performed during a 4-year period, according to WHO criteria of GEP - NET. MATERIAL AND METHODS: The study group comprised case records of 134 patients with confirmed GEP-NET carcinomas (WHO groups 2-4). All patients were subjected to clinical, biochemical and imaging examinations performed as routine clinical work-up. The imaging techniques consisted of anatomical (CT, EUS) and functional approaches (SRS, mIBG and FDG PET). RESULTS: The clinical classification considered the primary origin of the tumor as follows: 49% - foregut tumors, 44% - midgut, and 7% of tumors of unknown origin. Group of patients with WHO 2 consisted of 98 (73%) subjects. Considering those with foregut tumors EUS followed by CT and SRS were used in each case. SRS and CT imaging was used to assess the extent of the tumor. Patients with midgut tumors had CT and SRS as routine diagnostic imaging examinations. Considering the above-mentioned patients, CT and SRS were used to localize the primary tumor, and assess tumor extent. Overall sensitivity of CT considering the active disease amounted to 96%, while specificity - 75%. Sensitivity of SRS was 97%, while specificity- 85%. WHO 3-29 patients, 17 foregut and 9 midgut tumors, and 3 of unknown origin. Diagnostic imaging examinations consisted of CT. Standard SRS (sst2) was negative in most cases. The aggressive behaviour of this type of tumors was detected by means of FDG-PET. Sensitivity of CT amounted to 100%, and that of SRS - 44%. Specificity of CT amounted to 67% and that of SRS - 100%. WHO 4-7 patients, including 4 foregut and 3 midgut neoplasms. The imaging approach consisted of CT/MR and in 5 cases FDG-PET. Sensitivity of CT amounted to 100%. Only one patient presented with a SRS positive study. FDG-PET sensitivity amounted to 100%. CONCLUSION: Diagnostic imaging of GEP-NET, consider anatomical and functional techniques, which should be read together. The diagnostic value of CT and SRS were similar in case of WHO 2, while in case of WHO 3 CT had a higher diagnostic accuracy. FDG-PET seems to be a very attractive imaging functional modality in case of patients with WHO 3 and WHO 4.

Preservation of duodenal passage as a determinant of short- and long-term quality of life in gastric cancer patients after total gastrectomy.

BACKGROUND: The aim of this prospective study was to compare subjective and objective quality of life (QoL) of gastric cancer patients after total gastrectomy with and without preservation of the duodenal passage during short- and long-term follow-up. METHODS: The study included 68 patients, among them 37 (54%) persons subjected to total gastrectomy with Roux-Y reconstruction (R-Y group) and 31 (46%) individuals in whom gastrectomy was followed by formation of Henley-Longmire loop (H-L group). Subjective and objective QoL was determined 1 and 10 years postsurgery. During each visit, subjective QoL was determined with EORTC QLQ-C30 questionnaire, along with markers of nutritional status and self-reported incidence of symptoms specific to postgastrectomy syndrome. RESULTS: The two groups did not differ significantly in terms of their subjective QoL and markers of nutritional status at 1 and 10 years postsurgery, and none of these parameters underwent significant changes between the first and second evaluation. Patients from R-Y group reported subjective weight loss significantly more often during both visits, and individuals from H-L group significantly more often complained on postprandial diarrhea during long-term follow-up. Moreover, both groups showed an increase in the incidence of postprandial vomiting between the first and second evaluation. CONCLUSIONS: QoL of gastric cancer patients subjected to total gastrectomy stabilizes at relatively high level within a year from the surgery. Preservation of the duodenal passage does not exert a beneficial effect on both objective and subjective QoL after total gastrectomy.

HER2 Status in Advanced or Metastatic Gastric, Esophageal, or Gastroesophageal Adenocarcinoma for Entry to the TRIO-013/LOGiC Trial of Lapatinib.

HER2/ERBB2 status is used to select patients for HER2-targeted therapy. HER2/ERBB2 amplification/overexpression of upper gastrointestinal (UGI) adenocarcinomas was determined locally or in two central laboratories to select patients for the TRIO-013/LOGiC trial of chemotherapy with or without lapatinib. Patients selected locally had central laboratory confirmation of HER2 amplification for inclusion in the primary efficacy population. HER2 was assessed with PathVysion or IQ PharmDx FISH and HercepTest immunohistochemistry assays. Associations with outcomes were retrospectively evaluated. Overall, HER2 status was determined in UGI cancers from 4,674 patients in a central laboratory for eligibility (1,995 cases) and for confirmation of local HER2 results (333 cases). Of 1,995 adenocarcinomas screened centrally, 322 (16.1%) had HER2-amplified disease with 29 (1.5%) showing HER2 genomic heterogeneity. Men and older patients had higher rates of amplification. Of 545 patients accrued to the trial (gastric, 87.3%; GEJ, 8.3% and esophageal cancer, 4.4%), 487 patients (89%) were centrally confirmed as having HER2-amplified disease. Concordance between central and local HER2 testing was 83%. Concordance between PathVysion and IQ PharmDx FISH assays was 99% and FISH in the two central laboratories was 95%. Lapatinib-treated Asian participants and those less than 60 years had significant improvement in progression-free survival (PFS), particularly among those whose cancers had 5.01-10.0 and >10.0-fold amplification of HER2 In conclusion, HER2 is commonly amplified in UGI adenocarcinomas with amplification highly correlated to overexpression, and HER2 amplification levels correlated with PFS. While HER2 genomic heterogeneity occurs, its prevalence is low. Mol Cancer Ther; 16(1); 228-38. ©2016 AACR.

Lapatinib in Combination With Capecitabine Plus Oxaliplatin in Human Epidermal Growth Factor Receptor 2-Positive Advanced or Metastatic Gastric, Esophageal, or Gastroesophageal Adenocarcinoma: TRIO-013/LOGiC--A Randomized Phase III Trial.

PURPOSE: To evaluate the efficacy of adding lapatinib to capecitabine and oxaliplatin (CapeOx) in patients with previously untreated human epidermal growth factor receptor 2 (HER2) -amplified advanced gastroesophageal adenocarcinoma. PATIENTS AND METHODS: Patients with HER2-positive advanced gastroesophageal adenocarcinoma were randomly assigned at a one-to-one ratio to CapeOx plus lapatinib 1,250 mg or placebo daily. Primary end point was overall survival (OS) in patients with centrally confirmed HER2 amplification in the primary efficacy population. RESULTS: A total of 545 patients were randomly assigned, and 487 patients comprised the primary efficacy population. Median OS in the lapatinib and placebo arms was 12.2 (95% CI, 10.6 to 14.2) and 10.5 months (95% CI, 9.0 to 11.3), respectively, which was not significantly different (hazard ratio, 0.91; 95% CI, 0.73 to 1.12). Median progression-free survival in the lapatinib and placebo arms was 6.0 (95% CI, 5.6 to 7.0) and 5.4 months (95% CI, 4.4 to 5.7), respectively (hazard ratio, 0.82; 95% CI, 0.68 to 1.00; P = .0381). Response rate was significantly higher in the lapatinib arm: 53% (95% CI, 46.4 to 58.8) compared with 39% (95% CI, 32.9 to 45.3) in the placebo arm (P = .0031). Preplanned exploratory subgroup analyses showed OS in the lapatinib arm was prolonged in Asian and younger patients. No correlation was observed between HER2 immunohistochemistry status and survival. There were increased toxicities in the lapatinib arm, particularly diarrhea. CONCLUSION: Addition of lapatinib to CapeOx did not increase OS in patients with HER2-amplified gastroesophageal adenocarcinoma. There were clear differences in the effect of lapatinib depending on region and age. Future studies could examine this correlation.

Phase III randomized controlled trial comparing the survival of patients with unresectable hepatocellular carcinoma treated with nolatrexed or doxorubicin.

PURPOSE: The study objective was to compare the overall survival (OS) of patients with unresectable or metastatic hepatocellular carcinoma (HCC) treated with nolatrexed (NOL) or doxorubicin (DOX). PATIENTS AND METHODS: Patients from North America, Europe, and South Africa (N = 445) with HCC were randomly assigned to receive NOL or DOX. Eligible patients had Karnofsky performance status (KPS) > or = 60%, Cancer of the Liver Italian Program (CLIP) score < or = 3, and adequate organ function. Primary end point was OS. Secondary end points included progression-free survival (PFS), objective response rates, and safety. The treatment groups were well-balanced with regards to age, sex, ethnic origin, and underlying liver disease. Randomization was stratified according to KPS and CLIP score. RESULTS: At the time of the final analysis, 377 patients had died. Median OS was 22.3 weeks for NOL and 32.3 weeks for DOX (P = .0068). The hazard ratio was 0.753 in favor of DOX. Objective response rate (complete response [CR] plus partial response [PR]) was 1.4% for NOL and 4.0% for DOX. Median PFS was 12 weeks for NOL and 10 weeks for DOX (P = .7091). Median time to treatment failure was 8.4 weeks for NOL and 9.1 weeks for DOX (P = .0969). Grade 3 and 4 stomatitis, vomiting, diarrhea, and thrombocytopenia were more common in the NOL arm. Alopecia was more common in the DOX arm. More patients were withdrawn from study for toxicity in the NOL arm than in the DOX arm. CONCLUSION: NOL showed minimal activity in this phase III trial. Further exploration at this dose and schedule in HCC is not warranted.

Weekly infusional high-dose fluorouracil (HD-FU), HD-FU plus folinic acid (HD-FU/FA), or HD-FU/FA plus biweekly cisplatin in advanced gastric cancer: randomized phase II trial 40953 of the European Organisation for Research and Treatment of Cancer Gastrointestinal Group and the Arbeitsgemeinschaft Internistische Onkologie.

PURPOSE: This multicentric, randomized, two-stage phase II trial evaluated three simplified weekly infusional regimens of fluorouracil (FU) or FU plus folinic acid (FA) and cisplatin (Cis) with the aim to select a regimen for future phase III trials. PATIENTS AND METHODS: A total of 145 patients with advanced gastric cancer where randomly assigned to weekly FU 3,000 mg/m2/24 hours (HD-FU), FU 2,600 mg/m2/24 hours plus dl-FA 500 mg/m2 or l-FA 250 mg/m2 (HD-FU/FA), or FU 2000 mg/m2/24 hours plus FA plus biweekly Cis 50 mg/m2, each administered for 6 weeks with a 1-week rest. The primary end point was the response rate. RESULTS: Confirmed responses were observed in 6.1% (two of 33) of the eligible patients treated with HD-FU, in 25% (12 of 48, including one complete remission [CR]) with HD-FU/FA, and in 45.7% (21 of 46, including four CRs) with HD-FU/FA/Cis. The HD-FU arm was closed after stage 1 because the required minimum number of responses was not met. The median progression-free survival of all patients in the HD-FU, HD-FU/FA, and HD-FU/FA/Cis arm was 1.9, 4.0, and 6.1 months, respectively. The median overall survival was 7.1, 8.9, and 9.7 months, and the survival rate at 1 year was 24.3%, 30.3%, and 45.3%, respectively. Grade 4 toxicities were rare. The most relevant grade 3/4 toxicities were neutropenia in 1.9%, 5.4%, and 19.6%, and diarrhea in 2.7%, 1.9%, and 3.9% of the cycles in the HD-FU, HD-FU/FA, and HD-/FU/Cis arms, respectively. CONCLUSION: Weekly infusional FU/FA plus biweekly Cis is effective and safe in patients with gastric cancer.