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The discovery of human epidermal growth factor receptor 2 (HER2) overexpression in 15-20% of gastric adenocarcinomas has been a key advance in the global care of this disease. Validated by the ToGA trial in the first-line setting of advanced HER2-positive (+) gastric cancer (GC), trastuzumab, an anti-HER2 monoclonal antibody (mAb), was the first therapeutic agent to significantly improve the prognosis of these patients. Since these results, many attempts have been made to improve the clinical outcomes of patients with HER2+ GC. However, all the other HER2-targeting molecules have failed to show a survival benefit in large phase III studies. The value of continuing trastuzumab after disease progression has been suggested by several retrospective studies. However, recent results of a randomized phase II trial showed no benefit from this strategy. On the other hand, novel therapeutic methods, such as immunotherapy, are emerging as new tools in the strategy of care of advanced GC, even if their benefit in the specific HER2+ population remains undetermined. Furthermore, substantial progress has been made in the understanding of the mechanisms leading to resistance to anti-HER2 therapies, and in the screening methods to detect them, thus opening new perspectives. The aim of this review was firstly to summarize the existing data on the specific strategy of care of HER2+ advanced GC, and secondly, to describe current knowledge regarding the potential mechanisms of resistance to HER2-targeting therapies. Lastly, we report the prospects for overcoming these potential obstacles, from future therapeutic strategies to new detection methods.

Background: The correlation between immune cells and the Lauren classification subtypes and their prognostic impact in advanced gastric cancer (AGC) are unknown., Methods: Circulating natural killer (NK) cells, CD4 + and CD8 + T cells, regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) were quantified in peripheral blood mononuclear cells (PBMCs) from 67 patients with untreated AGC enrolled in the PRODIGE 17-ACCORD 20 trial. CD56 + cells (NK), CD8 + , and FoxP3 +  (Treg) tumor-infiltrating lymphocytes (TILs) were assessed in tumor samples., Results: Circulating NK and Treg proportions were significantly lower in patients with diffuse/mixed-type AGC (n = 27) than those with intestinal type (n = 40; median 6.3% vs 11.5%; p = 0.02 and median 3.3% vs 5.2%; p = 0.03, respectively). Proportions of circulating MDSC, CD4 + and CD8 + T cells were not associated with one pathological type. Among tumor-infiltrating cells, CD8 + T cells, but not NK or FoxP3 + cells, were significantly lower in diffuse/mixed-type AGC (median 21 vs 59 cells/field; p = 0.009). Patients with high circulating NK cell counts (> 17%) had a better overall survival than those with < 17% (HR 0.40; 95% CI [0.15-1.06]; p = 0.04). Patients with high CD8 + TIL counts (> 31 cells/field) had significantly longer overall survival (HR 0.44; 95% CI [0.21-0.92]; p = 0.02). The prognostic value of CD8 + TILs was maintained after adjustment for confounding factors, including the Lauren classification (HR = 0.42; 95% CI [0.18-0.96]; p = 0.039)., Conclusion: Diffuse/mixed-type AGC has lower rates of CD8 + TILs and circulating NK cells and Tregs than the intestinal type. This "cold tumor" phenotype may be associated with a worse outcome.

Most western countries have guidelines on anal cancer screening for men who have sex with men (MSM) living with HIV. However, adherence to these guidelines has been studied poorly. This cross-sectional study reports anal cancer screening uptake and identifies the factors associated with a previous screening in MSM living with HIV in a Paris Hospital (France). A total of 410 outpatients completed a self-administered questionnaire on anal cancer screening. The median age was 50 years and the median time from HIV diagnosis was 14.2 years. Overall, 82.2% of patients were aware of anal cancer screening and, of these, 56.7% had already undergone a screening test. The absence of history of screening (43.3%) was most often explained by lack of time (31.3%) or information (28.2%). Among patients familiar with the anal screening procedure, those older than 50 years (adjusted odds ratio=2.4, 95% confidence interval=1.3-4.7, P=0.007) and informed by healthcare providers (adjusted odds ratio=8.2, 95% confidence interval=2.5-32.0, P=0.001) were more likely to have already been screened. To date, adherence to anal cancer screening in MSM living with HIV appears to be inadequate to enable diagnosis of cancer at its early stages. Encouraging physicians to inform MSM living with HIV about anal cancer screening, irrespective of their age, could be an effective strategy to improve anal cancer screening uptake.

Purpose: This study aimed to estimate the accuracy of dual-phase C-arm cone beam computed tomography (CBCT) for the detection of colorectal cancer liver metastases, as compared with multidetector computed tomography (MDCT)., Materials and Methods: Between March 2014 and December 2016, 49 consecutive patients referred for intra-arterial treatment for colorectal cancer liver metastases were enrolled in a single-center observational study. All patients were examined with MDCT and with dual-phase C-arm cone beam computed tomography performed after iodine injection in the proper hepatic artery before intra-arterial treatment. Two blinded observers independently reviewed all examinations. Diagnostic accuracy was determined using both a six-cell matrix method and a "worst-case scenario.", Results: Readers identified at MDCT 264 colorectal liver metastases and 43 other liver lesions. The early and late arterial phase showed 240 and 277 liver lesions respectively. A certainty of the diagnosis was obtained in 63% and 85% at the early (EAP) and late arterial phase (LAP), respectively. Streak artifacts or liver segment truncation, or inadequate enhancement was responsible for the inability to see or to correctly adjudicate a lesion to a diagnosis in 27% and 15% of the cases at the EAP and LAP. The "worst-case scenario" yielded a Se and Sp of 58% and 51%, respectively, at EAP and 84% and 70%, respectively, at LAP., Conclusion: On CBCT, EAP showed limited accuracy. LAP provided the best tumor detectability., Key Points: • The early arterial phase (EAP) yielded poor accuracy: Se = 58% and Sp = 51% (p < 0.0001). • The late arterial phase (LAP) phase yielded good accuracy: Se = 84% and Se = 70% (p = 0.02). • The probability of a correct diagnosis at the EAP was 60%.

Purpose: To determine whether intraprocedural C-arm cone-beam CT (CBCT) parenchymal blood volume (PBV) can predict the response of colorectal cancer liver metastases (CRCLM) 2 months after irinotecan drug-eluting bead (DEBIRI) chemoembolization., Materials and Methods: This single-center observational study was compliant with the Helsinki Declaration and approved by our institutional review board. Thirty-four consecutive CRCLM patients referred for DEBIRI chemoembolization were enrolled between March 2015 and December 2016. Tumor size was assessed at baseline and 2 months after DEBIRI chemoembolization by multidetector CT (Response Evaluation Criteria in Solid Tumors RECIST 1.0), and PBV was measured before and after DEBIRI chemoembolization. Two independent readers reviewed all data. We determined the potential correlation (Spearman's rank correlation) between intraprocedural PBV values and tumor response at 2 months. The relationship between tumor response and PBV was studied using a mixed model. A logistic regression model was applied to study the relationship between patient "Responder/Non-responder" and PBV., Results: There was a strong correlation between baseline PBV or the percent change of PBV and the 2-month tumor response (rho = - 0.8587 (p = 0.00001) and rho = 0.8027 (p = 0.00001), respectively). The mixed model showed that an increase of 1 ml/1000 ml in PBV of a tumor before DEBIRI chemoembolization led to a 0.54 mm decrease in diameter (p < 0.005). A 1% decrease in PBV after DEBIRI chemoembolization resulted in tumor shrinkage of 0.75 mm (p < 0.005). The logistic regression model showed that patients with a 1% smaller mean decrease of PBV after DEBIRI chemoembolization had a 10% lower likelihood of achieving disease control (OR = 0.9, 95% confidence interval (CI) = 0.81-1; p = 0.0493)., Conclusion: Intraprocedural PBV may predict tumor response to DEBIRI chemoembolization., Key Points: • There is a strong relationship between the parenchymal blood volume (PBV) of colorectal liver metastases before DEBIRI chemoembolization and tumor response at 2 months. • Higher PBV values before DEBIRI chemoembolization correlate with greater tumor shrinkage, but only if the PBV decreases by more than 70% after DEBIRI chemoembolization. • Each increase of 1% in the mean decrease of PBV after DEBIRI chemoembolization resulted in a 10% lower likelihood of achieving disease control (OR = 0.9, 95% confidence interval (CI) = 0.81-1; p = 0.0493).

Background: Triplet chemotherapy, with docetaxel-5FU-oxaliplatin (TEFOX), has yielded promising results in patients with advanced and operable gastric adenocarcinoma. This may prove useful in treating signet ring cell carcinoma (SRCC), which is known to be chemoresistant and has a poor prognosis. We therefore evaluated TEFOX in patients with untreated advanced SRCC., Methods: Patients with metastatic or locally advanced non-resectable SRCC were treated with TEFOX. Chemotherapy was administered every 14 days, with combined docetaxel (50 mg/m 2 ) and oxaliplatin (85 mg/m 2 ) followed by 5FU (2400 mg/m 2 )., Results: Among 65 patients enrolled, including 17 with linitis plastica, ORR and DCR were 66.1% and 87.6%, respectively. Median PFS and OS were 9.7 months (95% CI [6.9-11.4]) and 14.3 months (95% CI [11.6-21.6]) respectively. Twenty-six patients (40%) initially considered as unresectable had secondary resection (n = 24) or radiotherapy (n = 2) with curative intent, with median PFS and OS of 12.4 and 26.2 months, respectively., Conclusions: TEFOX appears to be effective as first-line treatment in advanced gastric SRCC and has an acceptable safety profile. It allowed a curative intent approach in 40% of patients. Considering the low chemosensitivity of SRCC reported with other chemotherapy regimens and pending for randomised studies, TEFOX might be an option in advanced gastric SRCC.

Background: There is no consensus on screening strategy of high-grade intraepithelial neoplasia (HGAIN). Guidelines range from clinical examination with digital anorectal examination followed by standard anoscopy (SA), to anal cytology (Pap)+/- HPV genotyping. We compared screening strategy yields based on Pap, SA, and HPV-16 genotyping alone or in combination in HIV-MSM., Methods: Pap, SA, and HPV-16 genotyping were performed in all HIV-MSM attending a first anal cancer screening consultation in Paris, France. High-resolution anoscopy, the gold standard to detect HGAIN, was performed in the case of HPV-16 positivity or abnormal cytology. Yield was defined as the number of patients with HGAIN relative to the total number of patients screened., Results: On 212 patients, the complete strategy (SA + Pap + HPV genotyping) yield (12.7%) was significantly higher than that of SA (3.3%, p < 0.001) and HPV-16 alone (6.6%, p < 0.05). Although none of the other strategies were significantly different from the complete strategy, Pap + HPV-16 and Pap + SA had closer yields (about 11%), with OR = 0.83 (95% CI [0.44;1.57]) and 0.87 (95% CI [0.46;1.64]), respectively., Conclusions: Pap combined with HPV-16 genotyping or SA tended towards higher yields compared to Pap alone, and closer to that of the complete strategy.

Competing Interests: T. Voron déclare n’avoir aucun lien d’intérêts. S. Pernot déclare des liens ponctuels (interventions et/ou prise en charge lors de congrès) avec Amgen, Sanofi, BTG, Merck et Bayer.

Background: The identification of dynamic biomarkers in advanced gastric and oesogastric junction adenocarcinoma (GOA) could help to tailor strategies for each patient. Enumeration of circulating tumour cells (CTCs) is approved by the US Food and Drug Administration in breast, colon and prostate cancer but is not in advanced GOA. Our study aims to establish the optimal threshold and the clinical significance of CTC count in advanced GOA before and during treatment., Methods: One hundred six patients with untreated advanced GOA were included in the ancillary study of the PRODIGE 17-ACCORD 20 trial. CTCs were detected in the peripheral blood using the CellSearch system on day 0 (D0) and day 28 (D28). The prognostic value of CTCs at D0 and D28 was analysed by testing several thresholds., Results: At baseline, median CTC count was 1 (range, 0-415). While CTCs ≥1, 2 or 3 at D0 were all significantly associated with worse overall survival (OS) and progression-free survival (PFS), CTCs ≥2 were the optimal threshold, on D0 or D28. CTCs ≥2 at D28 were also predictive of disease control. Taking into account both D0 and D28 CTC count defined 3 groups (low/low, high/low and low-high/high) with significantly different PFS (p = 0.0002) and OS (p = 0.003)., Conclusion: Quantification of CTCs at baseline and during treatment may be a useful prognostic tool in advanced GOA, as it is associated with worse PFS and OS. A threshold ≥2 CTCs seems to have the best discriminant value. Change in CTC count between baseline and D28 could help to tailor treatment to each individual patient., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The objective of the treatment of colorectal cancer patients with unresectable liver metastases should be clearly defined at the outset. Potentially resectable patients should be distinguished from clearly unresectable patients. In defining resectability, it is important to take into account both anatomic characteristics and patient characteristic (comorbidities, symptoms, age). According to this evaluation, treatment should be tailored to each patient. The most widely accepted standard is doublet cytotoxic regimen plus biotherapy (anti-EGFR or anti-VEGF antibodies according to RAS status, but some patients could benefit from an intensified regimen, as triplet chemotherapy ± bevacizumab, or intraarterial treatments (hepatic arterial infusion, radioembolization or chemoembolization), in order to allow resectability. It is therefore very important to discuss the treatments with a multidisciplinary team, including an experienced surgeon, an interventional radiologist and an oncologist. On the other hand, some patients could benefit in terms of quality of life and decreased toxicity from less intense treatment when resection is not an objective. First-line monotherapy or a maintenance strategy with biotherapy and/or cytotoxics could be discussed with these patients, and treatment holidays should be considered in selected patients. Finally, in patients with secondary resection of liver metastases, specificity should be considered in choosing the best adjuvant treatment, such as response to preoperative treatment and individual risk of relapse, which many in some cases justify intensification with hepatic arterial infusion in an adjuvant setting.