PURPOSE Approximately 15% to 43% of esophageal adenocarcinomas (EACs) are human epidermal growth factor receptor 2 (HER2) positive. Because dual-agent HER2 blockade demonstrated a survival benefit in breast cancer, we conducted a phase II feasibility study of trastuzumab and pertuzumab added to neoadjuvant chemoradiotherapy (nCRT) in patients with EAC. PATIENTS AND METHODS Patients with resectable HER2-positive EAC received standard nCRT with carboplatin and paclitaxel and 41.4 Gy of radiotherapy, with 4 mg/kg of trastuzumab on day 1, 2 mg/kg per week during weeks 2 to 6, and 6 mg/kg per week during weeks 7, 10, and 13 and 840 mg of pertuzumab every 3 weeks. The primary end point was feasibility, defined as ≥ 80% completion of treatment with both trastuzumab and pertuzumab. An exploratory comparison of survival with a propensity score–matched cohort receiving standard nCRT was performed, as were exploratory pharmacokinetic and biomarker analyses. RESULTS Of the 40 enrolled patients (78% men; median age, 63 years), 33 (83%) completed treatment with trastuzumab and pertuzumab. No unexpected safety events were observed. R0 resection was achieved in all patients undergoing surgery, with pathologic complete response in 13 patients (34%). Three-year progression-free and overall survival (OS) were 57% and 71%, respectively (median follow-up, 32.1 months). Compared with the propensity score–matched cohort, a significantly longer OS was observed with HER2 blockade (hazard ratio, 0.58; 95% CI, 0.34 to 0.97). Results of pharmacokinetic analysis and activity on [18F]fluorodeoxyglucose positron emission tomography scans did not correlate with survival or pathologic response. Patients with HER2 3+ overexpression or growth factor receptor–bound protein 7 (Grb7) –positive tumors at baseline demonstrated significantly better survival ( P = .007) or treatment response ( P = .016), respectively. CONCLUSION Addition of trastuzumab and pertuzumab to nCRT in patients with HER2-positive EAC is feasible and demonstrates potentially promising activity compared with historical controls. HER2 3+ overexpression and Grb7 positivity are potentially predictive for survival and treatment response, respectively.

The tumor microenvironment plays an important role in the initiation and progression of pancreatic adenocarcinoma (PDAC). In this systematic review, we provide an overview of clinical trials with stroma-targeting agents. We systematically searched MEDLINE/PubMed and the EMBASE database, using the PRISMA guidelines, for eligible clinical trials. In total, 2330 records were screened, from which we have included 106 articles. A meta-analysis could be performed on 51 articles which describe the targeting of the vascular endothelial growth factor (VEGF) pathway, and three articles which describe the targeting of hyaluronic acid. Anti-VEGF therapies did not show an increase in median overall survival (OS) with combined hazard ratios (HRs) of 1.01 (95% confidence interval (CI) 0.90–1.13). Treatment with hyaluronidase PEGPH20 showed promising results, but, thus far, only in combination with gemcitabine and nab-paclitaxel in selected patients with hyaluronic acid (HA)high tumors: An increase in median progression free survival (PFS) of 2.9 months, as well as a HR of 0.51 (95% CI 0.26–1.00). In conclusion, we found that anti-angiogenic therapies did not show an increased benefit in median OS or PFS in contrast to promising results with anti-hyaluronic acid treatment in combination with gemcitabine and nab-paclitaxel. The PEGPH20 clinical trials used patient selection to determine eligibility based on tumor biology, which underlines the importance to personalize treatment for pancreatic cancer patients.

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First-line triplet chemotherapy including a taxane may prolong survival in patients with metastatic esophagogastric cancer. The added toxicity of the taxane might be minimized by using nab-paclitaxel. The aim of this phase I study was to determine the feasibility of combining nab-paclitaxel with the standard of care in the Netherlands, capecitabine and oxaliplatin (CapOx). Patients with metastatic esophagogastric adenocarcinoma received oxaliplatin 65 mg/m2 on days 1 and 8, and capecitabine 1000 mg/m2 bid on days 1–14 in a 21-day cycle, with nab-paclitaxel on days 1 and 8 at four dose levels (60, 80, 100, and 120 mg/m2, respectively), using a standard 3 + 3 dose escalation phase, followed by a safety expansion cohort. Baseline tissue and serum markers for activated tumor stroma were assessed as biomarkers for response and survival. Twenty-six patients were included. The first two dose-limiting toxicities (i.e., diarrhea and dehydration) occurred at dose level 3. The resulting maximum tolerable dose (MTD) of 80 mg/m2 was used in the expansion cohort, but was reduced to 60 mg/m2 after three out of eight patients experienced diarrhea grade 3. The objective response rate was 54%. The median progression-free (PFS) and overall survival were 8.0 and 12.8 months, respectively. High baseline serum ADAM12 was associated with a significantly shorter PFS (p = 0.011). In conclusion, albeit that the addition of nab-paclitaxel 60 mg/m2 to CapOx may be better tolerated than other taxane triplets, relevant toxicity was observed. There is a rationale for preserving taxanes for later-line treatment. ADAM12 is a potential biomarker to predict survival, and warrants further investigation.

Gender disparities in scientific publications have been identified in oncological research. Oral research presentations at major conferences enhance visibility of presenters. The share of women presenting at such podia is unknown. We aim to identify gender‐based differences in contributions to presentations at two major oncological conferences. Abstracts presented at plenary sessions of the American Society of Clinical Oncology (ASCO) Annual Meetings and European Society for Medical Oncology (ESMO) Congresses were collected. Trend analyses were used to analyze female contribution over time. The association between presenter's sex, study outcome (positive/negative) and journals' impact factors (IFs) of subsequently published papers was assessed using Chi‐square and Mann–Whitney U tests. Of 166 consecutive abstracts presented at ASCO in 2011–2018 (n = 34) and ESMO in 2008–2018 (n = 132), 21% had female presenters, all originating from Northern America (n = 17) or Europe (n = 18). The distribution of presenter's sex was similar over time (p = 0.70). Of 2,425 contributing authors to these presented abstracts, 28% were women. The proportion of female abstract authors increased over time (p < 0.05) and was higher in abstracts with female (34%) compared to male presenters (26%; p < 0.01). Presenter's sex was not associated with study outcome (p = 0.82). Median journals' IFs were lower in papers with a female first author (p < 0.05). In conclusion, there is a clear gender disparity in research presentations at two major oncological conferences, with 28% of authors and 21% of presenters of these studies being female. Lack of visibility of female presenters could impair acknowledgement for their research, opportunities in their academic career and even hamper heterogeneity in research.

10523 Background: Gender discrepancies have been identified in authorships of scientific publications, grant applications, and peer review in many disciplines, including oncology. The exact share of women presenting results of oncological studies at large conferences is unknown, while the oral presentation of a study at such a podium enhances the international visibility and recognition of the presenting person. Therefore, we aim to identify gender-based differences in contributions to presentations at two major oncological conferences. Methods: We collected consecutive abstracts presented at the plenary sessions of the American Society of Clinical Oncology (ASCO) Annual Meetings and presidential sessions of the European Society for Medical Oncology (ESMO) Congresses. Sex of the presenters and abstract authors, study results (positive vs. negative), and subsequently published papers were identified. Chi square tests were used to compare the distribution of sex over time. The association between presenter’s or last author’s sex and study outcome and impact factors were analyzed using Chi square tests and Mann-Whitney U tests, respectively. Results: Of available abstracts presented at ASCO between 2011 and 2018 (N = 34), and ESMO between 2008 and 2018 (N = 132), presenters were female in 24% and 21%, respectively. Female last authors were seen in 21% and 20% of these ASCO and ESMO abstracts. Of all contributing authors to these ASCO (N = 569) and ESMO (N = 1851) abstracts, 31% and 27% were female, respectively. The distribution of male and female ASCO and ESMO presenters (P = 0.580, P = 0.707, respectively) and abstract authors (P = 0.429, P = 0.062) was similar over the years. Of all abstracts, sex of the presenter or last abstract author were not associated with study outcomes (P = 0.718, P = 0.4331), nor with impact factor of subsequently published papers (P = 0.209, P = 0.661). Conclusions: There is a clear gender disparity in the presentation of oncological research at two main conferences, with less than a third of abstract authors female and less than a quarter of these studies presented by a woman. The lack of visibility of female researchers at presentations on these conferences could impair the acknowledgement for their research, opportunities in their academic career, and even hamper heterogeneity and outcomes in research.

PurposeAn acute coronary syndrome (ACS) is characterized by a multi-level inflammatory response, comprising activation of bone marrow and spleen accompanied by augmented release of leukocytes into the circulation. The duration of this response after an ACS remains unclear. Here, we assessed the effect of an ACS on the multi-level inflammatory response in patients both acutely and after 3 months.MethodsWe performed 18F-DPA-714 PET/CT acutely and 3 months post-ACS in eight patients and eight matched healthy controls. DPA-714, a PET tracer binding the TSPO receptor and highly expressed in myeloid cells, was used to assess hematopoietic activity. We also characterized circulating monocytes and hematopoietic stem and progenitor cells (HSPCs) by flow cytometry in 20 patients acutely and 3 months post-ACS and in 19 healthy controls.ResultsIn the acute phase, patients displayed a 1.4-fold and 1.3-fold higher 18F-DPA-714 uptake in, respectively, bone marrow (p = 0.012) and spleen (p = 0.039) compared with healthy controls. This coincided with a 2.4-fold higher number of circulating HSPCs (p = 0.001). Three months post-ACS, 18F-DPA-714 uptake in bone marrow decreased significantly (p = 0.002), but no decrease was observed for 18F-DPA-714 uptake in the spleen (p = 0.67) nor for the number of circulating HSPCs (p = 0.75).Conclusions18F-DPA-714 PET/CT reveals an ACS- triggered hematopoietic organ activation as initiator of a prolonged cellular inflammatory response beyond 3 months, characterized by a higher number of circulating leukocytes and their precursors. This multi-level inflammatory response may provide an attractive target for novel treatment options aimed at reducing the high recurrence rate post-ACS.Electronic supplementary materialThe online version of this article (10.1007/s00259-018-4038-8) contains supplementary material, which is available to authorized users.