Kia Homayounfar

805 Background: Multidisciplinary Tumor Boards (MDT) have been advocated as standard of care in modern oncology. German cancer guidelines for metastasized colorectal cancer (mCRC) recommend discussing every patient (pt) with colon cancer (CC) after primary surgery and every pt with clinical stage IV CC as well as every rectal cancer (RC) pt prior to any therapy in a MDT. In this study we evaluated how extensive this approach has been implemented in clinical routine and how MDT discussion influences treatment decisions within a representative region with established access to MDTs for all actors. Methods: All major institutions treating oncological pts in southern Lower Saxony and Northern Hesse (N = 11) were invited to participate in the study. Pts with mCRC and diagnosis of the first metastasis between 01/2011 and 12/2013 were eligible. A standardized pt report form was developed and data were collected in a GCP-conform EDC-system named secuTrial. Results: A university medical center, 4 teaching hospitals, 1 communal hospital and 3 oncological focus practices participated in the study. In total, 470 pts (CC n = 278, RC n = 192) with a median age of 70 (range 22-92) years were enrolled. 286 (60.9%) pts had synchronous and 184 (39.1%) pts had metachronous metastases. Discussion within an MDT was performed in 141 (62.9%) of 224 CC pts after primary surgery and in 70 (38.3%) of 183 pts with clinical stage IV CC prior to any therapy. In RC pts, MDT discussion prior to any therapy happened in 91 (47.4%) pts. Curative resection of metastases was performed in 193 (41.1%) cases. Pts > 70 years (n = 250) received significantly more often chemotherapy ± surgery when presented in an MDT (85.8% versus 64.4%, p = 0.0002). In pts with single organ metastases the resection rate was not significantly different (48.4% versus 56.9%, p = 0.1574) but preoperative chemotherapy was more often indicated (56.7% versus 33.3%, p = 0.0056) when pts were discussed in a MDT. Conclusions: In clinical routine MDT discussion is not as established as advocated by national guidelines. Treatment decisions differ depending on MDT discussion especially in older pts and those with single organ metastases.

BACKGROUND: In previous work, a single administration of anticarcinoembryonic antigen (anti‐CEA) ¹³¹I‐labetuzumab radioimmunotherapy (RIT) after complete resection of colorectal liver metastases was well tolerated and significantly improved survival compared with controls. In the current phase 2 trial, the authors studied repeated RIT in the same setting, examining safety, feasibility, and efficacy.METHODS: Sixty‐three patients (median age, 64.5 years) received RIT at 40 to 50 millicuries/m² per dose. Before the receipt of RIT, restaging was performed with computed tomography/magnetic resonance imaging and ¹⁸F‐fluorodeoxyglucose–positron emission to confirm that patients were “truly adjuvant.” Patients who had elevated serum CEA levels or radiographically inconclusive new lesions were classified as “possibly nonadjuvant,” but they also received RIT. Time to progression (TTP), overall survival (OS), and cause‐specific survival (CSS) were calculated. The median follow‐up was 54 months.RESULTS: After the first course of RIT, 14 of 63 patients experienced National Cancer Institute Common Toxicity Criteria grade 4 hematotoxicity; 19 patients did not receive the second course of RIT because of impaired performance status (N = 5) or relapse (N = 14). After the second course of RIT, 9 of 44 patients experienced National Cancer Institute Common Toxicity Criteria grade 4 hematotoxicity. Five patients developed myelodysplastic syndrome (MDS) from 22 to 55 months after their last RIT. The median TTP, OS, and CSS for all patients were 16, 55, and 60 months, respectively. The “truly adjuvant” patients (N = 39) had an improved median TTP (not reached vs 6.1 months; hazard ratio, 0.12; P < .001), OS (75.6 vs 33.4 months; hazard ratio, 0.44; P = .014), and CSS (not reached vs 41.4 months; hazard ratio,0.42; P = .014) compared with “possibly nonadjuvant” patients (N = 24).CONCLUSIONS: Repeated RIT with ¹³¹I‐labetuzumab is feasible but is associated with hematotoxicity. Survival is very encouraging, especially for “truly adjuvant” patients. However, the maximum safe dose of ¹³¹I‐labetuzumab is a single administration of 50 millicuries/m². Cancer 2017;123:638–649. © 2016 American Cancer Society.

Hintergrund Verdrängungswettbewerb, Kostendruck, Generation Y, Ärztemangel und Feminisierung beeinflussen das Personalmanagement in der Viszeralchirurgie. Die Einschätzung der Istsituation durch die Abteilungsleiter (AL) sowie die Übertragbarkeit von Strategien aus Industrie und Dienstleistungsgewerbe (ID) wurden bisher nicht untersucht. Material und Methoden Mittels eines standardisierten Fragebogens mit 43 Items wurden AL an Universitätskliniken und Krankenhäusern mit ≥ 800 Planbetten befragt (n = 100). Geschlossene Fragen wurden anhand einer 5-stufigen Likert-Skala gestaltet. Zehn Personalverantwortliche (PV) aus ID wurden zur Teilnahme an einem 45-minütigen Telefoninterview eingeladen. Ergebnisse An der Befragung nahmen 37 AL teil, davon 15 Lehrstuhlinhaber. Initiativbewerbung (100%) sowie Stellenanzeigen (78%) und Ansprache von PJ-Studenten (78%) waren die häufigsten Wege der Personalgewinnung. Einen standardisierten Vorbereitungsbogen für Vorstellungsgespräche nutzten nur 17% der AL. Fachkompetenz (MW 2,2 ± 0,9), Sozialkompetenz (MW 1,9 ± 0,6) und gute Deutschkenntnisse (MW 1,8 ± 0,8) wurden als bedeutsame Voraussetzungen für eine Einstellung genannt. Referenzen und Zeugnissen (MW 3,2 ± 0,9) wurde wenig Bedeutung beigemessen. Die Mitarbeiterförderung wurde für sehr wichtig gehalten (MW 1,1 ± 0,2), ein fester Zeitrahmen für die Weiterbildung jedoch nur bedingt zugesichert (MW 3,0 ± 1,5). Transparente Anforderungsprofile für einen Aufstieg (MW 2,5 ± 1,1) und unterschiedliche Karrieremodelle (MW 2,7 ± 1,2) waren wenig vorhanden. Am Telefoninterview nahmen 6 PV teil. Die Mitarbeiterabwerbung (75%), Internet-Plattformen (75%), Werbung auf Messen (75%) sowie Anwerbung von Auszubildenden (50%), Stellenanzeigen (50%) und Social Media (50%) waren häufig genannte Wege der Personalgewinnung. Fach- und Führungskarrieren sind oft voneinander getrennte Karrierepfade, wobei Sozialkompetenz entscheidend für die Besetzung von Führungspositionen ist. Schlussfolgerung In der Viszeralchirurgie sind Initiativbewerbung, Stellenanzeige und PJ-Studenten die Hauptwege zur Personalgewinnung. Diversifizierte Fach- und Führungskarrieren sind bisher nicht etabliert. In ID erfolgreiche Maßnahmen wie aktives Scouting sowie Social Media sollten ebenso evaluiert werden wie diversifizierte Karrieremodelle. Background Cut-throat competition, cost pressure, generation Y, shortage of qualified staff and feminisation influence human resources management in visceral surgery. The assessment of the current situation by chief surgeons (CS) as well as proof of transferability of strategies from industry and service business (ISB) have not yet been investigated. Material and Methods The CS of university hospitals and large referral centres (> 800 beds) were interviewed (n = 100) on the basis of a standardised questionnaire including 43 items. Closed questions were designed with a 5-point Likert scale and their analysis was presented as means (MW) and standard deviations (±). Ten human resources manager (HMR) of ISB were invited to participate in 45-minute telephone interviews. Results Thirty-seven CS participated in the survey, 15 of whom were full professors. Unsolicited applications (100%), job advertisements (78%) and direct approaches to final year students (78%) were the most common ways of recruitment. Only 17% of CS used a standardised form for preparation. Professional expertise (MW 2.2 ± 0.9), social skills (MW 1.9 ± 0.6) and excellent German language skills (MW 1.8 ± 0.8) were named as important qualifications for employment, while references and certificates were regarded as being less important (MW 3.2 ± 0.9). Personal development was regarded as important (MW 1.1 ± 0.2), but a defined period for residency was not guaranteed (MW 3.0 ± 1.5). Transparent selection criteria for career opportunities (MW 2.5 ± 1.1) and different career models (MW 2.7 ± 1.2) were only rarely available. Six HRM participated in the interviews. Active head-hunting (75%), Internet platforms (75%), presentations at conferences (75%), as well as hiring trainees (50%), job advertisements (50%) and social media (50%) were established options to find qualified employees. Professional and management careers were often separate career paths, while social expertise was regarded as being crucial for filling management positions. Conclusion In visceral surgery, unsolicited applications, job advertisements and direct approaches to final year students are the most common ways for recruitment. Diversified professional and management careers are not yet established. Recruiting strategies that are successful in ISB – such as active scouting and use of social media – should be evaluated for visceral surgery, as well as diversified career models.

575 Background: The development of metachronous distant metastasis is – despite remarkable progress - still a challenging problem after multimodality treatment of rectal cancer. The host immune response has been identified as a valid prognostic marker in primary colon cancer but not in rectal cancer after neoadjuvant chemoradiotherpy so far. Methods: We analysed the mRNA and protein expression of the B- and T-cell chemokines CXCL13 and CXCL9 as well as the B-cell marker IGHM in 77 rectal cancer specimens undergoing preoperative chemoradiotherapy and investigated the role of the host immune response on the occurrence of distant metastasis and survival. Results: The intratumoral mRNA expression levels of the T-cell activator CXCL9 (p < 0.001) as well as the B-cell chemokine CXCL13 (p < 0.01) were inversely correlated with the development of distant metastasis. Patients with high CXCL9 (p < 0.0001) or CXCL13 expression (p < 0.01) had a significantly prolonged DFS. Moreover, patients with high mRNA levels of both CXCL9 and CXCL13 had an excellent DFS compared to patients without expression of any of the chemokines (p < 0.0001). Additionally, CXCL9 expression was correlated with an improved CSS (p < 0.05). There was no significant correlation between the B-cell marker IGHM and metastasis or survival. Conclusions: The host immune response represented by intratumoral expression levels of the lymphocyte-activating chemokines CXCL9 and 13 is associated with reduced rates of distant metastases and improved survival in rectal cancers after multimodality treatment. Further investigations are needed to prospectively validate these results and characterize the underlying cellular and molecular mechanisms.

Background Multidisciplinary discussion of the treatment of patients with colorectal liver metastases (CRLM) is advocated currently. The aim of this study was to investigate medical oncologists' and surgeons' assessment of resectability and indication for chemotherapy, and the effect of an educational intervention on such assessment. Methods Medical histories of 30 patients with CRLM were presented to ten experienced medical oncologists and 11 surgeons at an initial virtual tumour board meeting (TB1). Treatment recommendations were obtained from each participant by voting for standardized answers. Following lectures on the potential of chemotherapy and surgery, assessment was repeated at a second virtual tumour board meeting (TB2), using the same patients and participants. Results Overall, 630 answers (21 × 30) were obtained per tumour board meeting. At TB1, resectability was expected more frequently by surgeons. Participants changed 56·8 per cent of their individual answers at TB2. Assessment shifted from potentially resectable to resectable CRLM in 81 of 161 and from unresectable to (potentially) resectable CRLM in 29 of 36 answers. Preoperative chemotherapy was indicated more often by medical oncologists, and overall was included in 260 answers (41·3 per cent) at TB1, compared with only 171 answers (27·1 per cent) at TB2. Medical oncologists more often changed their decision to primary resection in resectable patients (P = 0·006). Postoperative chemotherapy was included in 51·9 and 52·4 per cent of all answers at TB1 and TB2 respectively, with no difference in changes between medical oncologists and surgeons (P = 0·980). Conclusion Resectability and indication for preoperative chemotherapy were assessed differently by medical oncologists and surgeons. The educational intervention resulted in more patients deemed resectable by both oncologists and surgeons, and less frequent indication for chemotherapy.

567 Background: Even though treatment options for coloretal cancer liver metastases have improved with the implementation of multimodal strategies and new agents, progression of distant metastases is still limiting the prognosis of affected patients. In this context we investigated the expression of HER2 and HER3 in patients with metastatic colorectal cancer and primary tumors. Methods: In this study 226 consecutive patients with hepatic metastases of colorectal cancer were included. HER2 and HER3 expression were determined in the tissue from resected metastases and—if available—in primary tumors. Immunohistochemical scoring (IHC 0 to IHC 3) and S-ISH-amplification-detection (for HER2) were used to determine the HER2 and HER3 status. Results: A positive HER2 status was found in 8.4% of all hepatic metastases; an overexpression of HER-3 in 74,8% of all cases. There was a high congruence of the expression pattern of HER2 and HER3 between hepatic metastases and available primary tumors (>90%). Conclusions: HER2 amplification and HER3 overexpression is detectable in a significant proportion of hepatic metastases of colorectal cancer. These results suggest that innovative new targeted treatment agents might be possible opportunities for the specific therapy of patients with HER2/HER3 positive metastatic colorectal cancer and should be further assessed within prospective clinical trials.

546 Background: Preoperative radiochemotherapy (RCT) followed by total mesorectal excision (TME) has improved local tumor control and led to a significant tumor downstaging. For patients with pathologic complete response (ypT0) as well as residual tumor restricted only to the bowel wall (ypT1-2) local excision has increasingly been discussed to avoid significant morbidity and functional deficits associated with TME. Therefore we investigated the incidence, distribution and tumor-related localization of mesorectal lymph node (LN) metastases in TME specimens with ypT0, ypT1-2 and ypT3-4 rectal cancers, respectively. Methods: TME specimens from 81 patients with locally advanced rectal cancer treated with neoadjuvant RCT within the phase III German Rectal Cancer Trial CAO/ARO/AIO-04 were evaluated. The entire mesorectal compartment was screened microscopically after complete paraffin embedding. The number and localization of all detectable LN metastases was specified in relation to the primary tumor. Results: Whereas 50 patients (62%) had ypT3-4 carcinomas after neoadjuvant RCT 20 patients (25%) presented with residual tumor within the bowel wall (ypT1-2). 11 patients (14%) had pathologic complete response (ypT0). 28 ± 13.7 LN were detected per specimen. 25 patients (31%) had residual LN metastases after RCT. Although the incidence was higher in the ypT3-4 group (40% ypN+) still 25% of patients in the ypT1-2 group had a mean number of 2.2 residual LN metastases. 55% of these metastases were located afar from the primary lesion in the proximal mesorectum. No patient with ypT0 status had residual LN metastases. Conclusions: Even in patients with good response and tumors restricted only to the bowel wall (ypT1-2) after RCT there is a considerable risk for residual LN metastases. The majority of metastases were located clearly outside the tumor region. Local excision of residual rectal cancer would be accompanied by a higher rate of local failure and radical surgery with TME should remain the standard treatment in those patients.

Purpose Surgery is the standard of care for resectable colorectal liver metastases (CRC-LM). Unfortunately, 60 % of patients develop secondary metastatic recurrence (SMR) after R0-resection of CRC-LM. We investigated the impact of surgical re-intervention and chemotherapy (Ctx) on survival in a consecutive series of patients with SMR. Methods From 01/2001 to 11/2011, 104 out of 178 consecutive patients with R0-resection of CRC-LM developed SMR and were evaluated. The impact of surgical and Ctx re-interventions on recurrence free (RFS) and cancer-specific survival (CSS) was analyzed. Median follow-up was 28.0 (95 %CI: 19.4–37.4) months. Results SMR occurred in 81 patients at a single site (49× liver, 18× lung, 14× other) and in 23 patients at multiple sites. Forty-two patients were scheduled for primary surgery. Fifty-three patients were classified as non-resectable and treated with median 5.0 [IQR, 3.0–10.0] cycles of Ctx, combined with an EGFR/VEGF-antibody in 27 patients. Nine patients received best supportive care only. R0/R1 resection could be achieved in 35 patients primarily and even in 8 patients secondarily after Ctx. Surgical morbidity and mortality were 16 and 0 %, respectively. The 5-year RFS rates for patients with R0 versus R1-resection were 22 and 24 % (p = 0.948). The 5-year CSS rate for R0/R1-resected patients was 38 % versus 10 % for those patients treated by Ctx alone (p < 0.001). Conclusion In SMR, surgical re-intervention is feasible and safe in a remarkable number of patients and offers significantly longer CSS compared to patients without resection.