Starting the fight in the tumor: expert recommendations for the development of human intratumoral immunotherapy (HIT-IT).

A European Society for Medical Oncology (ESMO)-sponsored expert meeting was held in Paris on 8 March 2018 which comprised 11 experts from academia, 11 experts from the pharmaceutical industry and 2 clinicians who were representatives of ESMO. The focus of the meeting was exclusively on the intratumoral injection/delivery of immunostimulatory agents with the aim of harmonizing the standard terms and methodologies used in the reporting of human intratumoral immunotherapy (HIT-IT) clinical trials to ensure quality assurance and avoid a blurring of the data reported from different studies. The goal was to provide a reference document, endorsed by the panel members that could provide guidance to clinical investigators, pharmaceutical companies, ethics committees, independent review boards, patient advocates and the regulatory authorities and promote an increase in the number and quality of HIT-IT clinical trials in the future. Particular emphasis was placed not only on the development of precise definitions to facilitate a better understanding between investigators but also on the importance of systematic serial biopsies as a driver for translational research and the need for the recording and reporting of data, to facilitate a better understanding of the key processes involved.

HER3 expression in patients with primary colorectal cancer and corresponding lymph node metastases related to clinical outcome.

AIM: To evaluate the expression and prognostic value of the epidermal growth factor receptor HER3 in patients with primary colorectal cancer (CRC) and corresponding lymph node metastases. PATIENT AND METHODS: HER3 expression was analysed immunohistochemically (IHC) in primary tumours and in corresponding lymph node metastases from 236 patients with stage II and III CRC. In 58 primary tumours, fluorescence in situ hybridisation (FISH) detection was performed. RESULTS: HER3 was detected at high frequency in the cell membrane. Seventy percent of the primary tumours had a high HER3 expression compared to 75% in the lymph node metastases. HER3 expression in the primary tumour was an independent prognostic factor for overall survival in the entire group of patients (p=0.026) and in the subgroup of patients with colon cancer stage II (p=0.030). A high HER3 expression in the primary tumour was associated with worse clinical outcome. The expression of HER3 was homogenous within the primary tumour (r=0.9, p<0.0001) and correlated with the HER3 expression in corresponding lymph node metastases (r=0.6, p<0.0001). No gene amplification with respect to HER3 was seen in primary tumours using FISH analysis. CONCLUSION: A high HER3 expression was found in 70% of the primary CRC tumours and in 75% of the corresponding lymph node metastases. HER3 expression in the tumour was an independent prognostic factor, where a high HER3 expression was associated with worse clinical outcome. There was a correlation in HER3 expression between primary tumour and corresponding lymph node metastases.

Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): the NORDIC NEC study.

BACKGROUND: As studies on gastrointestinal neuroendocrine carcinoma (WHO G3) (GI-NEC) are limited, we reviewed clinical data to identify predictive and prognostic markers for advanced GI-NEC patients. PATIENTS AND METHODS: Data from advanced GI-NEC patients diagnosed 2000-2009 were retrospectively registered at 12 Nordic hospitals. RESULTS: The median survival was 11 months in 252 patients given palliative chemotherapy and 1 month in 53 patients receiving best supportive care (BSC) only. The response rate to first-line chemotherapy was 31% and 33% had stable disease. Ki-67<55% was by receiver operating characteristic analysis the best cut-off value concerning correlation to the response rate. Patients with Ki-67<55% had a lower response rate (15% versus 42%, P<0.001), but better survival than patients with Ki-67≥55% (14 versus 10 months, P<0.001). Platinum schedule did not affect the response rate or survival. The most important negative prognostic factors for survival were poor performance status (PS), primary colorectal tumors and elevated platelets or lactate dehydrogenase (LDH) levels. CONCLUSIONS: Advanced GI-NEC patients should be considered for chemotherapy treatment without delay.PS, colorectal primary and elevated platelets and LDH levels were prognostic factors for survival. Patients with Ki-67<55% were less responsive to platinum-based chemotherapy, but had a longer survival. Our data indicate that it may not be correct to consider all GI-NEC as one single disease entity.

Prognostic and predictive value of thymidylate synthase expression in primary colorectal cancer.

AIM: To investigate thymidylate synthase (TS) expression in primary colorectal cancer (CRC) as a prognostic and predictive marker of benefit for adjuvant chemotherapy. PATIENTS AND METHODS: TS expression was immuno0-histochemically (IHC) assessed on tumors from 1,389 patients with stage II and III CRC randomly assigned to either surgery alone or surgery plus 5-fluorouracil (5-FU)-based adjuvant chemotherapy. RESULTS: In the subgroup treated with surgery alone (n=708), TS expression was prognostic using the classification of TS 0-1 versus 2-3 (p=0.045) as well as TS classified as 0-2 versus 3 (p=0.002). A high TS expression was associated with a shorter overall survival. Among patients with TS grade 3 (n=460), the subgroup treated with adjuvant chemotherapy had a significant longer OS (p=0.005). CONCLUSION: In this study TS, immunohistochemically assessed, is a prognostic factor in CRC patients treated with surgery alone. Patients with the highest level of TS expression (grade 3) had an improved clinical outcome following adjuvant 5-FU-based chemotherapy.

The meaning of preceptorship: nurses' lived experience of being a preceptor.

AIM OF THE STUDY: This phenomenological study is aimed at illuminating nurses' lived experience of the process of preceptoring and the meaning of preceptorship in a Swedish context. METHODS: Seventeen nurses from the North of Sweden with varied previous experience of preceptorship volunteered to participate. Their narratives, describing their experience of being a personal preceptor for a student nurse during practical training on a hospital ward in the third year of a 3-year diploma programme within a university college of nursing in Sweden, were transcribed verbatim. A phenomenological-hermeneutic interpretation disclosed the themes 'sheltering the students when learning' and 'facilitating the students' learning', together with eight sub-themes, which created an understanding of the meaning of preceptorship. FINDINGS AND DISCUSSION: The meaning of preceptorship was understood as reducing the risk of the students learning helplessness and empowering the students when learning in practice. The meaning of preceptorship highlighted the need for further preceptor support and development of the role of the preceptor. On the basis of the findings, suggestions were made to increase the preceptors' awareness of values in nursing practice and use of pedagogical strategies in the process of preceptoring. Through such strategies a reciprocal development of the preceptors' and the faculty's knowledge may take place, to the best advantage of the students' learning and the development of the profession.

Nurses' lived experience of being a preceptor.

Registered nurses' lived experience of preceptorship was studied in this phenomenological study. To illuminate the meaning of registered nurses' experience of being a preceptor for student nurses, individual tape-recorded interviews were conducted with 17 registered nurses. They narrated their experience of being a personal preceptor for student nurses during practical training on a hospital unit, and the interviews transcribed verbatim were analyzed phenomenological-hermeneutically. The analysis revealed two main themes (1) including the student in their daily work and (2) increasing awareness of the process of learning, as well as six other themes, which contributed to a new comprehension of the meaning of being a preceptor. All the themes were related to the ongoing preceptor-preceptee relationship. The preceptors' thinking on past experiences and their ideas of nursing care in the future were present simultaneously. Nurses acting as preceptors were perceived as conscious individuals, demanding a balance of their daily work responsibility with increased awareness of the professional demands of nursing care. Preceptors gained increased awareness of and a desire to fulfill the student nurses' varied learning needs and increased awareness of their own learning process.

Student nurses' lived experience of preceptorship. Part 1--in relation to learning.

In this first part of a research project a phenomenological approach was applied to understanding student nurses' experience of preceptorship. The lived experience of seventeen student nurses learning within a preceptor-preceptee relationship on hospital wards formed the basis of the study. Tape-recorded interviews were conducted, transcribed and analysed. The phenomenological hermeneutic analysis revealed three themes of meaning central to the lived experience of learning. These were (a) directing learning; (b) learning in practical action and (c) feeling in learning. The themes included six sub-themes with internal variations. The results indicate that learning, as a phenomenon, could be understood as being in different modes of learning, including directing learning, learning in practical actions and feeling in learning. Each theme was also found to be inherent in the others in an ongoing changeable process. The findings were compared with Aristotle's five modes of learning and revealed that the student nurses' learning embraced scientific knowledge, technical skills, practical wisdom and limited intuition. The study may provide nurse educators with some insight into student nurses' learning by being in real-life situations and performing nursing actions within a preceptor-preceptee relationship.

Student nurses' lived experience of preceptorship. Part 2--the preceptor-preceptee relationship.

Student nurses' experience of preceptorship was the focus of this second part of a phenomenological study. The aim was to illuminate student nurses' lived experience of the preceptor-preceptee relationship on hospital wards. A phenomenological-hermeneutic analysis was made of tape-recorded interviews with seventeen student nurses. The interpretation process culminated in four themes, namely: (a) creating space for learning; (b) providing concrete illustrations; (c) exercising control and (d) seeking reflection. Each theme included sub-themes with internal variations. The theme 'creating space for learning' was understood as basic in relation to the other themes and as the foundation of student learning and preceptoring. The ongoing process of preceptoring meant that the preceptors acted as role models, were with the students and also exercised control. Control was directed both to patient safety and to student learning. The students' 'seeking reflection' included attempts to find peace and quiet either by themselves or with the preceptor. The reflection together with the preceptor facilitated the students' transformation of knowledge, from the specific situation to a general knowledge and increased the value of learning.