Antonio Viudez

Pancreatic neuroendocrine tumors: Challenges in an underestimated disease

Pancreatic neuroendocrine tumours (PanNETs) are considered a relatively unusual oncologic entity. Due to its relative good prognosis, surgery remains the goal standard therapy not only in localized disease but also in the setting of locally or metastatic disease. Most of the patients are diagnosed in metastatic scenario, where multidisciplinary approach based on surgery, chemotherapies, liver-directed and/or molecular targeted therapies are commonly used. Owing to a deeper molecular knowledge of this disease, these targeted therapies are nowadays widely implemented, being the likely discovery of predictive biomarkers that would allow its use in other settings. This review is focused on describing the different classifications, etiology, prognostic biomarkers and multidisciplinary approaches that are typically used in PanNET.

Determinants of patient satisfaction with care in a Spanish oncology day hospital and its relationship with quality of life.

This study evaluates satisfaction with care (SC) in cancer patients treated at a Spanish day hospital to identify SC determinants and assess the relationship between SC and quality of life.

The cancer outpatient satisfaction with care questionnaire for chemotherapy, OUT-PATSAT35 CT: a validation study for Spanish patients

PurposeThe OUT-PATSAT35 CT questionnaire evaluates satisfaction with care expressed by cancer outpatients receiving chemotherapy. This study assesses the psychometric properties of the OUT-PATSAT35 CT when applied to a sample of Spanish patients.MethodsOne hundred seventy-six patients with different tumour sites and disease stages completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ)-C30, the OUT-PATSAT35 CT, the Oberst patients’ perception of care quality and satisfaction scales (OS) and the item on intention to recommend the hospital (IR). Psychometric evaluation of the structure, reliability and validity of the questionnaire was conducted.ResultsMultitrait scaling analysis showed that 32 of 34 item-scale correlation coefficients met the standards for convergent validity and that many of them met the standards for discriminant validity. Cronbach’s coefficients were good (0.78–0.97) for all scales except doctor availability and environment. Correlations between the QLQ-C30 and the OUT-PATSAT35 CT were low (≤0.40). Correlations between IR and the OUT-PATSAT35 CT were moderate, and correlations between this questionnaire and the OS were fairly low. Areas whose contents were more related had higher correlation coefficients (>0.50) and vice versa (<0.1). Male patients, elderly patients, those with higher education levels, those with higher scores in four OS and patients who had not received surgery showed higher satisfaction with care in several OUT-PATSAT35 CT areas.ConclusionsThe OUT-PATSAT35 CT is a reliable and valid instrument when applied to a sample of Spanish cancer patients. These results are in line with those of the validation study conducted by the authors of the questionnaire and with the validation study for Spain of the OUT-PATSAT35 RT.

Safety and clinical activity of vascular endothelial growth factor receptor (VEGFR)- tyrosine kinase inhibitors after programmed cell death 1 inhibitor treatment in patients with metastatic clear cell renal cell carcinoma

BACKGROUND Emerging agents blocking the programmed cell death 1 (PD-1) pathway show activity in metastatic clear cell renal cell carcinoma (mRCC). The aim of this study was to evaluate the efficacy and safety of vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)-tyrosine kinase inhibitor (TKI) therapy after PD-1 inhibition. PATIENTS AND METHODS Patients with mRCC treated with anti-PD-1 antibody (aPD-1) monotherapy or in combination (with VEGFR-TKI or ipilimumab) that subsequently received VEGFR-TKI were retrospectively reviewed. The efficacy end points were objective response rate (ORR) and progression-free survival (PFS) stratified by the type of prior PD-1 regimen. Safety by the type and PD-1 exposure was also evaluated. RESULTS Seventy patients were included. Forty-nine patients received prior therapy with immune checkpoint inhibitors (CPIs) alone and 21 had combination therapy of aPD-1 and VEGFR-TKI. Overall, ORR to VEGFR-TKI after PD-1 inhibition was 28% (19/68) and the median PFS was 6.4 months (mo) (4.3-9.5). ORR to VEGFR-TKI after aPD-1 in combination with VEGFR-TKI was lower than that in patients treated with VEGFR-TKI after CPI alone (ORR 10% versus 36%, P = 0.039). In the multivariable analysis, patients treated with prior CPI alone were more likely to achieve an objective response than those treated with aPD-1 in combination with VEGFR-TKI (OR = 5.38; 95% CI 1.12-26.0, P = 0.03). There was a trend toward numerically longer median PFS in the VEGFR-TKI after the CPI alone group, 8.4 mo (3.2-12.4) compared with 5.5 mo (2.9-8.3) for those who had VEGFR-TKI after aPD-1 in combination with VEGFR-TKI (P = 0.15). The most common adverse events (AEs) were asthenia, hypertension, and diarrhea. CONCLUSIONS The efficacy and safety of VEGFR-TKIs after PD-1 inhibition were demonstrated in this retrospective study. The response rate was lower and the median progression-free survival was shorter in those patients who received prior PD-1 in combination with VEGFR-TKI. PD-1 exposure does not seem to significantly influence the safety of subsequent VEGFR-TKI treatment.

Quality of life assessment by applying EORTC questionnaires to rectal cancer patients after surgery and neoadjuvant and adjuvant treatment

BACKGROUND Quality of Life (QoL) is a key element in rectal cancer (RC) patients. AIMS this study assesses QoL in a sample of RC patients in their treatment follow-up period, and compares surgery modalities. PATIENTS AND METHODS eighty four locally advanced RC patients who had received surgery and neoadjuvant chemoradiotherapy were included in the study. Of these, 70 had adjuvant chemotherapy. All patients completed the EORTC QLQ-C30 and the QLQ-CR29 once at least one year after completion of their treatment. Low anterior resection (LAR) patients also completed a Functional Evaluation questionnaire. RESULTS QoL scores in the EORTC questionnaires for the sample as a whole were high in most dimensions, in line with the general population´s QoL values, although moderate limitations (> 30 points)were observed in urinary frequency, flatulence, impotence and sexual function. The scores for the Functional Evaluation were adequate (mean combined bowel function score of 18.2). LAR patients had a higher stool frequency than those with abdominoperineal resection (APR; p < 0.001). No differences in body image were found amongst LAR and APR patients. LAR patients with a lower anastomosis had higher faecal incontinence (p = 0.02), whereas those with a reservoir had better emotional functioning (p = 0.04) and higher faecal incontinence (p = 0.03). CONCLUSIONS QoL scores and functional evaluation indicated patients had adapted to their disease and treatment. The few differences in QoL found between surgery modalities are in line with other recent studies and in contrast with earlier ones that suggested a lower QoL in APR patients.

Effects of adjuvant oxaliplatin on anal function in locally advanced rectal cancer treated with preoperative chemoradiotherapy and low anterior resection.

718 Background: The main purpose of the present study was to determine if the addition of adjuvant oxaliplatin (OXA) could have some influence on sphincter function in patients with locally advanced rectal cancer (LARC) treated with preoperative capecitabine/radiotherapy followed by lower anterior resection (LAR). Methods: Those patients with LARC treated at our center with LAR and without two-years loco-regional relapse were retrospectively analyzed independent of the type of adjuvant treatment received. Anal sphincter function was assessed by Wexner´s incontinence score (0 to 20 points, being punctuation inversely proportional to sphincter function). All questionnaires were completed between January 2010 and December 2012. Comparisons of sphincter function measured with the Wexner test between patients with and without OX were conducted with the Mann-Whitney test. Statistical analyses were conducted using IBM SPSS Statistics, version 20. Results: From 2006, 92 consecutive patients were included in our s...

Clinical guide SEOM: hepatocellular carcinoma (HCC): considerations on SBRT.

We have read with great interest the article ‘‘Clinical guide SEOM: hepatocellular carcinoma’’ [1] and we would like to suggest some considerations: Effectively, although surgical management could be considered the standard of care for localized disease, most of the patients with HCC could not be considered surgical candidates and are managed with nonsurgical locoregional interventions. In this sense, we firmly believe that different options to local ablative treatments the radiofrequency ablation (RFA), and the percutaneous ethanol injection (PEI)) could be used in this scenario, such as microwave ablation, cryoablation and, especially, stereotactic body radiation therapy (SBRT). As the author point out, RFA achieves excellent rates in terms of local control (between 70 and 90 % for small tumors, smaller than 2 cm diameter), getting complete necrosis in only 30–40 % of tumors larger than 3 cm [2]. Nowadays SBRT could be considered as an emerging noninvasive alternative to RFA with similar local control rates [3]. Unlike RFA, increasing tumor size has not been linked to an increased local failure with this innovative technique. Although non-operable patients with localized HCC are typically candidates for both SBRT and RFA, from our knowledge there is no mature data comparing these modalities. Actually there is only one ongoing randomized trial comparing both modalities in patients with hepatic metastasis (ClinicalTrials.gov Identifier: NCT01233544). Unfortunately, the ‘‘Radiofrequency Ablation Versus Stereotactic Radiotherapy in Colorectal Liver Metastases (RAS01)’’ randomized trial from Aarhus University Hospital, Dennmark, was prematurely closed because of poor recruitment. Nevertheless, increasing information about the role of SBRT in local control and survival rate in HCC are continuously published [4]. In this sense, in February 2016, Wahl and colleagues published their experience at University of Michigan with 224 patients with inoperable, non-metastatic HCC treated by SBRT or RFA from 2004 to 2012 [5]. Based on their results, both arms were comparable in most of the variables. Oneand 2-year Local-Relapse-Free Survival for patients treated with RFA were 83.6 and 80.2 % vs 97.4 and 83.8 % for SBRT. The author concluded that both, RFA and SBRT, could be considered as local treatment options for inoperable HCC even when, although when based on the retrospective nature of this data, SBRT appears to be a reasonable first-line treatment of inoperable, larger HCC. In locally non-resectable HCC and based on previous considerations we firmly believe that, SBRT should be also considered.

Retrospective analysis of pathologic response in colorectal cancer liver-only metastases following treatment with bevacizumab.

674 Background: Recent reports have shown that pathological response predicts for better outcome (overall survival) following preoperative chemotherapy and surgical resection of colorectal cancer (CRC) liver-only metastases. The aim of this retrospective analysis was to evaluate the effect of adding bevacizumab to standard chemotherapy on pathological response in patients with CRC liver only metastases. METHODS Patients with stage IV CRC with liver metastases who received neoadjuvant chemotherapy (oxaliplatin-or irinotecan-based) at two Spanish centres were analysed retrospectively. Pathological response was evaluated as follows: complete pathological response (cPR), PR1 (25% of residual tumour), PR2 (25-50% of residual tumour), PR3 (>50% of residual tumour). cPR or PR1 was considered to be a good response, and PR2 or PR3 a poor response. RESULTS A total of 81 patients were evaluated. Of these, 43 received chemotherapy alone and 38 received chemotherapy plus bevacizumab. Baseline characteristics were as follows: median age 61.0 years (range 43.0-80.0 years); male/female (67%/33%); tumour location - colon (69%) / rectum (31%); hepatic metastases - synchronous (74%) / metachronous (26%); In terms of pathological response, 58% of patients receiving bevacizumab had a good response (cPR + PR1) compared with 28% of those receiving chemotherapy alone. At the end of the analysis, 68% of patients were still alive. CONCLUSIONS Adding bevacizumab to oxaliplatin-based chemotherapy in the neoadjuvant setting improves the pathological response of liver metastases in patients with stage IV CRC. These findings indicate that pathological response might be a good indicator of outcome for patients receiving bevacizumab in the neoadjuvant setting.

Role of presurgery circulating cancer cells (CTCs) as a potential pronostic factor in patients (pts) with liver surgery (LS) of colorectal cancer (CRC) metastases (M).

518 Background: Kinetic behavior of perioperative CTCs in pts with liver CRC M has been little explored. The aim of this study was to quantified CTCs performance before, just performed and 3 months after radical LS in pts with CRC M and analyzed the surrogate role of CTCs determinations in DFS and OS. METHODS 7.5 ml of blood were drawn in CellSave tubes. CTCs were enumerated before, just performed and 3 months after radical LS. CTCs were immunomagnetically separated and fluorescently labeled using the CellSearch System (Veridex/Immunicon Corp.) Results: From February 2009 to August 2011, 30 pts with LS of CRC M were included. Median age was 59 (45-75); 63.3 % men. Kras status: 63.2% wild-type and 36.8% mutated; 46.7% with synchronous disease. Fong-Criteria (FC) distribution: 30% pts with 1 FC, 36.7% pts with 2 FC and 33.3% pts with 3 FC, of whom 56.7% received neoadjuvant (76.4% fluoropirimidines-based; 29% cetuximab-based; 47% bevacizumab-based) and 73.3% adjuvant treatment. PR and SD were observed in 68.8% and 31.3% of pts, respectively (100% DCR). In 83% of cases, limited LS were done (79.3% R0, median M resected: 2), 20% of pts with synchronous surgery of primary tumour. Of the 15 pts analysed, pCR were observed in 2 (13.3%) with 6 other pts (40%) with major pathological response. With a median of follow-up of 21 months, progression disease occurred in 9 pts (55.6% with liver progression), and 4 pts died. Median CTCs was 0 before (0-2: 85%; ≥3: 14.8%), just performed (0-2: 78%; ≥3: 21%) and 3 months after surgery (0-2: 94.1%; ≥3: 5.9%). DFS for pts with pre-surgery CTCs ≥3 was 10 months, and not reached for 0-2 CTCs group. OS has not been achieved in any CTCs group. In the multivariate analysis, with FC and pre-surgery CTCs, pre-surgery CTCs ≥3 tends to be an independent predictor of outcome (HR: 2.83; CI:0.53-15). CONCLUSIONS Independently of neoadjuvant treatment, pre-surgery CTCs levels ≥3 could be a surrogate of short DFS in pts with LS of CRC M. Our study shown a slight increase in CTCs quantification after LS, instead a significant CTCs decrease was observed after adjuvant therapy. Role of radical LS in kinetic of CTCs should continue to be analysed in future studies.

Evolution of circulating tumor cells (CTCs) during neoadjuvant treatment and radical surgery in patients (pts) with liver-only metastases of colorectal cancer (L-CRC).

e14146 Background: The presence of baseline ≥ 3 (CTCs) in 7.5 mL of blood is predictive of a poor outcome in advanced colorectal cancer (JCO, 26;19: 3213-3221, 2008). The aim of this prospectively. study was to quantified CTCs performance during neoadjuvant treatment and before/after radical surgery in pts with L-CRC. METHODS From February 2009 to October 2010, 18 pts with L-CRC were included. Median age was 61 years old (48-79), 55.6% men. K-Ras status was: 54% wild-type; 46% mutated. 7.5 mL of blood were drawn in CellSave tubes. CTCs were isolated and enumerated at baseline, before and just performed radical liver surgery. CTCs were immunomagnetically separated and fluorescently labeled using the CellSearch System (Veridex/Immunicon Corp.). RESULTS Baseline determination was < 3 CTCs in 72.2 % of pts, and increased to 77.8% just before liver surgery. A slight decreased in pts with < 3 CTCs was observed after liver surgery (70.6%). CONCLUSIONS Unlike the published data of CTCs before/after liver surgery in systemic circulation (JCO, 20;27:6160-5, 2009), our study shown a modest increased in CTCs after liver metastases resection of advanced CRC. Role of radical metastases surgery in kinetic of CTCs must be analyzed in future studies.