Knowledge about hereditary nonpolyposis colorectal cancer; mutation carriers and physicians at equal levels

<p>Abstract</p> <p>Background</p> <p>Identification and adequate management of individuals at risk for hereditary nonpolyposis colorectal cancer (HNPCC) is crucial since surveillance programmes reduce morbidity and mortality. We investigated knowledge about key features of HNPCC in at risk individuals and physicians in surgery, gynecology and oncology.</p> <p>Methods</p> <p>Data were collected using a questionnaire which was answered by 67 mutation carriers and 102 physicians from the southern Swedish health care region. The statements were related to colorectal cancer, heredity and surveillance and the physicians were also asked questions about cancer risks and surveillance strategies.</p> <p>Results</p> <p>Both groups answered questions on colorectal cancer risk, surveillance and genetic testing well, whereas answers about inheritance and risks for HNPCC associated cancer were less accurate. Only half of the family members and one third of the physicians correctly estimated the risk to inherit an HNPCC predisposing mutation. Among family members, young age (<57 years), female sex and recent genetic counseling significantly correlated with better results. Physicians generally underestimated the risk of HNPCC associated cancers and three out of four suggested a later starting age for surveillance than recommended.</p> <p>Conclusion</p> <p>The finding of similar levels of knowledge about key features of HNPCC in at risk individuals and physicians reflect the challenge physicians face in keeping up to date on hereditary cancer and may have implications for the clinical management and professional relations with HNPCC family members.</p

Effects of Research Funding, Gender and Type of Position on Research Collaboration Networks: A Micro-level Study of Cancer Research at Lund University

The aim of this study is to analyse the extent of which different types of research funding, gender and type of position have an effect on the size and density of research collaboration networks. The material consists of 3,306 documents by scientists doing cancer research at Lund University, indexed in the Web of Science databases. The author and address fields were analysed, by studying frequencies and distribution of authors and organizations, and by conducting co-authorship analyses on the organizational level. The results show substantial differences between scientists with funding from the Swedish Cancer Society (SCS) in comparison with those without SCS funding. When comparing men and women, as well as scientists with preclinical positions and those combining clinical and pre-clinical work; there are larger differences between e.g. women with or without SCS funding than between men and women with SCS funding. The general applicability of these results might be limited; they only take one certain kind of funding into account and they analyses are performed on documents coming out of one particular context. In this case, however, the results suggest that research funding have a larger impact on the size and nature of research collaboration networks than gender or type of position

Väntetider i cancervården är en patientsäkerhetsfråga - Risken för cancerrelaterad morbiditet och sämre överlevnad behöver uppmärksammas.

Waiting times in cancer care is a patient safety risk that needs increased attention. Mechanisms and effects need to be clarified, waiting time statistics should be openly presented and evidence--based strategies should be implemented. Cancer patient pathways are implemented in Sweden during 2015-2018 and are expected to reduce waiting times for some patient groups, but cannot be expected to present a complete solution to the waiting time problem. Strategic work on waiting times requires knowledge about the differ-ent symptom profiles in various cancer types, understanding of the impact from waiting times in different cancer types and increased knowledge about the mechanisms in the health care system that cause waiting times

Patients' and physicians' disagreement on patients' understanding of clinical cancer trial information:a pairwise pilot study of mirroring subjective assessments compared with objective measurements

Background: Informed consent is a prerequisite for patients included in clinical trials. Trial design, inclusion criteria and legal requirements are increasingly complex. This complexity challenges design and delivery of written and oral trial information to ensure understandable information. To evaluate the level of concordance between patients' and informing physicians' assessments regarding patient understanding of trial information, we carried out a study based on paired questionnaire data from patients and their physicians. These assessments of patient understanding were further correlated with patients' factual knowledge of the information provided. Methods: This pilot study included patients and physicians immediately after the patients had received information on one of 23 ongoing phase III randomised cancer trials at two Swedish sites. In total, 46 patients and 17 physicians contributed data based on two new questionnaires with seven mirroring questions, where concordance was analysed with McNemar's test. These assessments of patients' self-estimated understanding were further correlated with the Patient Understanding of Research (Q-PUR) questionnaire that assesses factual knowledge of the information provided. Results: For each question, 47-61% of the patient-physician pairs were in concordance regarding their assessments of patients' 'fully understanding' or 'not fully understanding' various aspects of the trial information. For the discordant pairs, the physicians rated patient understanding lower than the patients themselves, for all seven questions. This difference was significant for five of the questions (P ≤ 0.017). The median Q-PUR knowledge score was 11 out of 12, but this score did not significantly correlate with the assessments, either from patients or from physicians. Conclusions: This study demonstrated a trend for physicians to rate the level of understanding of trial information among potential trial patients lower than the patients themselves. Application of Q-PUR revealed high knowledge scores, but without correlation to the assessments. These findings need validation in an independent setting, with an improved instrument with mirroring questions, and a better-matched measurement of patients' factual knowledge. These results suggest that physicians need to improve their ability to assess patient understanding of clinical trial information, in order to be able to tailor the patients' information individually

Delays in the Management of Retroperitoneal Sarcomas

Retroperitoneal sarcomas are rare and treatment should optimally be centralized. Despite successful centralization with 90% of the patients referred prior to surgery, delays occur, which led us to assess lead times in a population-based series. Method. Patients diagnosed with retroperitoneal sarcoma in the southern Sweden health care region 2003–2009 were eligible for the study. Data on referrals and diagnostic investigations were collected from clinical files from primary health care, local hospitals, and from the sarcoma centre. Lead times were divided into patient delays and health care delays caused by primary health care, local hospitals, or procedures at the sarcoma centre. Results. Complete data were available from 33 patients and demonstrated a median patient delay of 23 days (0–17 months) and median health care delay of 94 days (1–40 months) with delays of median 15 days at the general practitioner, 36 days at local hospitals, and 55 days at the sarcoma centre. Conclusion. Centralization per se is not sufficient for optimized and efficient management. Our findings suggest that delays can be minimized by direct referral of patients from primary health care to sarcoma centers and indicate that development of coordinated diagnostic packages could shorten delays at the sarcoma centre

Experiences from treatment-predictive KRAS testing; high mutation frequency in rectal cancers from females and concurrent mutations in the same tumor

BACKGROUND: KRAS mutations represent key alterations in colorectal cancer development and lead to constitutive EGFR signaling. Since EGFR inhibition represents a therapeutic strategy in advanced colorectal cancer, KRAS mutation analysis has quickly been introduced as a treatment-predictive test.METHODS: We used a real-time PCR based method to determine KRAS mutations in 136 colorectal cancers with mutations identified in 53 (39%) tumors.RESULTS: KRAS mutations were significantly more often found in rectal cancer (21/38, 55%) than in colon cancer (32/98, 33%) (P = 0.02). This finding was explained by marked differences mutation rates in female patients who showed mutations in 33% of the colon cancers and in 67% of the rectal cancers (P = 0.01). Concurrent KRAS mutations were identified in three tumors; two colorectal cancers harbored Gly12Asp/Gly13Asp and Gly12Cys/Gly13Asp and a third tumor carried Gly12Cys/Gly12Asp in an adenomatous component and additionally acquired Gly12Val in the invasive component.CONCLUSION: The demonstration of a particularly high KRAS mutation frequency among female rectal cancer patients suggests that this subset is the least likely to respond to anti-EGFR therapies, whereas the observation of concurrent KRAS mutations imply that repeated KRAS targeting may occur during tumor progression in a subset of colorectal cancers

Immunohistochemical Loss of the DNA Mismatch Repair Proteins MSH2 and MSH6 in Malignant Fibrous Histiocytomas

Purpose: Soft tissue sarcomas (STS) account for less than 1% of all malignancies and constitute a heterogeneous tumor entity in which malignant fibrous histiocytomas (MFH) represent one-third and are characterized by a lack of type-specific differentiation. A defective mismatch repair (MMR) system cause the familial cancer syndrome hereditary non-polyposis colorectal cancer (HNPCC), and since occasional MFH have been described in HNPCC patients we assessed the contribution of defective MMR to the development of MFH

Focus on the Tumour Periphery in MRI Evaluation of Soft Tissue Sarcoma: Infiltrative Growth Signifies Poor Prognosis

Purpose. Infiltrative microscopical peripheral growth of soft tissue sarcomas (STS) has been shown to be of prognostic importance and preoperative risk stratification could individualize neoadjuvant treatment. Patients and methods. We assessed peripheral tumour growth pattern on preoperative MRI from 78 STS. The findings were correlated to histopathology and to outcome. Results. The MRI-based peripheral tumour growth pattern was classified as pushing in 34 tumours, focally infiltrative in 25, and diffusely infiltrative in 19. All tumours with diffuse infiltration on MRI also showed microscopical infiltration, whereas MRI failed to identify infiltration in two-thirds of the microscopically infiltrative tumours. Diffusely infiltrative growth on MRI gave a 2.5 times increased risk of metastases (P = .01) and a 3.7 times higher risk of local recurrence (P = .02). Discussion. Based on this observation we suggest that MRI evaluation of STS should focus on the peripheral tumour growth pattern since it adds prognostic information of value for decisions on neoadjuvant therapies

Transcriptional impairment of β-catenin/E-cadherin complex is not associated with β-catenin mutations in colorectal carcinomas

We report the absence of β-catenin mutations in 63 sporadic colorectal carcinomas (SCRCs) with demonstrated decreased β-catenin and E-cadherin mRNA expression and E-cadherin protein expression in a subset of carcinomas examined, suggesting that β-catenin mutations are an extremely rare phenomenon in SCRCs and are not responsible for the transcriptional impairment of the β-catenin/E-cadherin adhesion complex observed in these tumours