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Objective the main objective was to assess repeatability and learning effect of the six-minute walk test (6MWT) in a cohort of preoperative cancer patients referred to a prehabilitation program. As a secondary objective we aimed to identify determinants of improvement in the second test. Materials and Methods secondary analysis from a large prospective study on the implementation of a multimodal prehabilitation program in a real-life scenario. Eligible patients were assessed at baseline before starting the prehabilitation program. The 6MWT was conducted according to the American Thoracic Society (ATS)/ European Respiratory Society (ERS) guidelines with two tests being performed under identical conditions separated by 30 minutes. The distance covered (in meters) and the physiological responses (heart rate, oxygen saturation, fatigue and dyspnea) to each test were recorded and compared. Results 170 patients (60.9%) were analyzed. Repeatability of the distance covered with the 6MWT was excellent (ICC = 0.98; 95% CI: 0.92 – 0.99), but a mean increase of +19.5 meters (95% CI: 15.6 - 23.5m; p=

Spanish Ministry of Education Culture and Sport, Grant/Award Number: FPU17/00939; Universidad de Granada/CBUA, Background: Aquatic therapeutic exercise can be equally effective or even superior to land-based exercise in improving several clinical variables. However, there is still a lack of knowledge on the effects compared to land-based interventions particularly in breast cancer (BC) patients. Objective: The objective of this study is to examine the effects of aquatic therapeutic exercise on pain, shoulder mobility, lymphedema, cardiorespiratory fitness, muscle strength, body composition, pulmonary function, cancer-related fatigue (CRF) and health-related quality of life (HRQoL) and which parameters are effective compared to similar land-based interventions. Methods: The databases used were PubMed, Scopus, Web of Science, Cochrane Library and CINAHL, retrieving 145 articles. Results: Eleven studies were included. Aquatic therapeutic exercise is feasible, safe, well tolerated and achieved high percentages of adherence. As for the assessed outcomes, moderate to large improvements were found compared to usual care or to land-based physical exercise interventions in pain, shoulder range of motion, pulmonary function, HRQoL, cardiorespiratory fitness and muscle strength. Inconclusive results were found for lymphedema, body composition and CRF. Conclusions: Aquatic therapeutic exercise interventions using a combination of endurance, strength, mobility, stretching and breathing exercises resulted in improvements in common side effects of BC and its treatments. More studies on CRF, body composition and lymphedema need to be done to further evaluate the impact of the intervention on these outcomes., Spanish Ministry of Education Culture and Sport FPU17/00939, Universidad de Granada/CBUA

Estudio de los polimorfismos del gen de la timidilato sintasa y los genes reparadores del ADN ERCC1 y XRCC1 y su relación con la rdespuesta al tratamiento neoadyvante con qumiorradioterapia basada en capecitabin, en pacientes afecto de carcinoma colorrectal de localmente avanzado. Estudi dels polimorfismes del gen de la timidilato sintasa i els gens reparadors del ADN ERCC1 i XRCC1 i la seva relació amb la reposta al tractament neoadjuvant amb quimiorradioterapia basada en capacitabina, en pacients afectes de carcinoma colorrectal localmente avançat.

Colorectal cancer (CRC) brain metastases (BM) are an uncommon and late event. We aim to investigate the impact of clinical factors, treatment modalities and RAS/BRAF status on the outcomes of CRC patients with BM. We retrospectively analysed CRC patients who developed BM in our centre between January 1997 and June 2017. Clinical factors, treatment modalities, RAS/BRAF status and survival were evaluated. Twenty-eight patients were recorded; 82% had left-sided (LS) CRC and 71% had lung metastases. Median time to BM diagnosis was 36 months (m) and 93% of patients received local treatment of BM (43% whole brain radiotherapy, 50% surgery). Right-sided (RS) CRC showed shorter time to BM, not previously described (9.3 vs 46.6 m for RS and LS CRC, respectively; HR = 4.7, p = 0.006). Median overall survival (mOS) from BM treatment was 9.5 m, better in patients who underwent surgery than those treated with radiotherapy alone (12.1 vs 4.6 m, respectively; HR = 0.3, p = 0.019) and in those without progressive metastatic extracranial disease (7.2 vs 20.9 m, for progressive and non-progressive, respectively; HR = 0.3, p = 0.056). Patients with two or more metastatic extracranial locations showed worse prognosis (5.9 vs 16.3 m, for > 2 vs 0–1, respectively; HR = 3.7, p = 0.015). RAS/BRAF status did not showed prognostic value. Time to BM diagnosis is shorter in RS CRC. The presence of two or more metastatic extracranial locations and progressive metastatic extracranial disease at the time of BM diagnosis could be bad prognosis factors for CRC BM patients.

Objectives: To investigate the effects of a preoperative pulmonary rehabilitation programme in patients with lung cancer undergoing video-assisted thoracic surgery. Design: Randomized, single-blind controlled trial. Setting: Teaching hospital. Subjects: Patients with suspected or confirmed lung cancer undergoing video-assisted thoracic surgery. Intervention: Participants were randomized to either a prehabilitation group or a control group. Participants in the prehabilitation group underwent a combination of moderate endurance and resistance training plus breathing exercises three to five times per week. Main measures: The primary outcome of the study was exercise capacity. Secondary outcomes were muscle strength (Senior Fitness Test), health-related quality of life (Short-Form 36) and the postoperative outcomes. Patients were evaluated at baseline (before randomization), presurgery (only the prehabilitation group), after surgery and three months post-operatively. Results: A total of 40 patients were randomized and 22 finished the study (10 in the prehabilitation group and 12 in the control group). Three patients were lost to follow-up at three months. After the training, there was a statistically significant improvement in exercise tolerance (+397 seconds, p = 0.0001), the physical summary component of the SF-36 (+4.4 points, p = 0.008) and muscle strength ( p Conclusions: A pulmonary rehabilitation programme before video-assisted thoracic surgery seems to improve patients’ preoperative condition and may prevent functional decline after surgery. Clinical Registration Number: NCT01963923 (Registration date 10/10/2013)

Background Hepatic resection of liver metastases is considered the optimal potentially curative treatment for colorectal liver metastases. Numerous clinical and pathological factors have been proved to be prognostic. The Genetic And Morphological Evaluation (GAME) has been proposed as a preoperative prognostic tool to select patients candidates for liver resection. This study aimed to validate the utility of GAME score risk groups in patients with colorectal liver metastases that underwent hepatic resection. Methods Clinical and pathological data were collected from 142 metastatic colorectal cancer patients undergoing liver resection (48% after neoadjuvant chemotherapy) between August 1999 and February 2018 at Sant Pau Hospital. The GAME score was calculated allocating points for KRAS mutation, CEA levels, lymph node metastasis, Tumour Burden score (TBS) and extrahepatic disease. We analysed the progression free survival (PFS) and overall survival (OS) according to the GAME score risk groups. Additionally, we considered other KRAS, NRAS and BRAF mutations not included in the original GAME score. Histopathological changes in malignant tissue and liver parenchyma were documented to identify potential prognostic factors for tumor recurrence. Results The high-risk group (GAME score ≥ 4 points) had a median PFS of 15.8 months compared with 24.2 months for the low-risk group (GAME score 0–1 point; p = 0.019). The high-risk group had a medium OS of 38.6 months compared with 68.8 months for the low-risk group (p = 0.05). When all RAS and BRAF status was considered regardless of the GAME score a median OS of 66.2 months was observed in wild type tumours compared to 44.5 months for mutated tumours (p = 0.005). Histological examination showed that a mixed and infiltrative growth pattern and the absence of a fibrotic pseudocapsule or liver cell rosettes were associated with a worse outcome. Conclusions The GAME score was validated as a useful preoperative prognostic tool in our cohort of patients. However, in our series, molecular profile was a prognostic factor regardless of the GAME score. Some pathologic characteristics may help on further clinical decisions after liver resection. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Lung cancer is the leading cause of cancer-related death worldwide. For early stages of the disease, lung resection surgery remains the best treatment with curative intent, but significant morbidity is associated, especially among patients with poor pulmonary function and cardiorespiratory fitness. In those cases, the implementation of a preoperative exercise-based intervention could optimize patient's functional status before surgery and improve postoperative outcomes and enhance recovery. The aim of this systematic review is to provide the current body of knowledge regarding the effectiveness of a preoperative exercise-based intervention on postoperative and functional outcomes in patients with lung cancer submitted to lung resection surgery. A systematic review of the literature using CINAHL, EMBASE, MEDLINE, Pubmed, PEDro and SCOPUS was undertaken in September 2015 yielding a total of 1656 references. Two independent reviewers performed the assessment of the potentially eligible records against the inclusion criteria and finally, 21 articles were included in the review. Articles were included if they examined the effects of an exercise-based intervention on at least one of the selected outcomes: pulmonary function, (functional) exercise capacity, health-related quality of life (HRQoL) and postoperative outcomes (length of stay and postoperative complications). Fourteen studies were further selected for a meta-analysis to quantify the mean effect of the intervention and generate 95% confidence intervals (CIs) using the Cochrane Review Manager 5.0.25. For two of the outcomes included (exercise capacity and HRQoL), studies showed large heterogeneity and thus, a meta-analysis was considered inappropriate. Pulmonary function (forced vital capacity and forced expiratory volume in 1 s) was significantly enhanced after the intervention [standardized mean difference (SMD) = 0.38; 95% CI 0.14, 0.63 and SMD = 0.27, 95% CI 0.11, 0.42, respectively]. In comparison with the patients in the control groups, patients in the experimental groups spent less days in the hospital (mean difference = -4.83, 95% CI -5.9, -3.76) and had a significantly reduced risk for developing postoperative complications (risk ratios = 0.45; 95% CI 0.28, 0.74). In conclusion, preoperative exercise-based training improves pulmonary function before surgery and reduces in-hospital length of stay and postoperative complications after lung resection surgery for lung cancer.

Estudio de los polimorfismos del gen de la timidilato sintasa y los genes reparadores del ADN ERCC1 y XRCC1 y su relación con la rdespuesta al tratamiento neoadyvante con qumiorradioterapia basada en capecitabin, en pacientes afecto de carcinoma colorrectal de localmente avanzado. Estudi dels polimorfismes del gen de la timidilato sintasa i els gens reparadors del ADN ERCC1 i XRCC1 i la seva relació amb la reposta al tractament neoadjuvant amb quimiorradioterapia basada en capacitabina, en pacients afectes de carcinoma colorrectal localmente avançat.

Background Leucine-rich and immunoglobulin-like domains (LRIG) 1, 2, and 3 are integral membrane proteins recently discovered as regulators of the epidermal growth factor (EGF) signalling. LRIG1 negatively regulates growth factor signaling and increasing evidence indicates that LRIG1 is a tumor suppressor in certain cancer types. Lrig1 is expressed at low levels in several cancer types but is overexpressed in some colorectal tumors. We postulate that polymorphisms located in the LRIG1 gene could influence the EGFR signalling pathway and be related with the clinical outcome in metastatic colorectal cancer (mCRC). Methods We studied 126 mCRC treated with a first-line oxaliplatin/5-fluorouracil chemotherapeutic regimen. Common and putatively functional polymorphisms in the LRIG gene were selected using public literature resources and databases (NCBI, PubMed, db SNP, Ensembl and GeneCards Version 3). These germline polymorphisms were analyzed using a Fluidigm equipment in DNA samples extracted from peripheral blood. Overall survival (OS) was evaluated according to each genotype. Results Two non-synonymous (c3158A > C and c1843A > G) and two synonymous (c2221T > C and c1317C > T) common and putatively functional polymorphisms in the LRIG1 gene were selected. There were significant associations between LRIG1 c1317C > T and c3158A > C polymorphisms and clinical outcome. OS was lower for patients harboring a T/T genotype than for patients with the C/C or C/T genotypes (p= 0.01). In the case of the c3158A > C polymorphism, patients harboring a C/C genotype had a lower OS than patients with an A/A or A/C genotypes (p = 0.047). Conclusions In this study, we identified common germline variants in LRIG1 gene predicting clinical outcome in patients with mCRC receiving first-line oxaliplatin-based chemotherapy. Disclosure All authors have declared no conflicts of interest.

Background EGF (epidermal growth factor) pathway is the main target of anti-EGFR (epidermal growth factor receptor) drugs in colorectal cancer. Although K-Ras mutation has been identified as a strong predictor of resistance to anti-EGFR therapy in mCRC (metastatic colorectal cancer), not all wild type patients respond to treatment. Several ligands have been proved to bind to EGFR such as amphiregulin (AREG) and epiregulin (EREG). The aim of this study is to analyze the role of polymorphisms in these ligands as pharmacogenetic markers for anti-EGFR treatment. Methods A total of 75 refractory mCRC patients were analyzed. All patients were K-Ras and B-Raf wild type and treatment consisted of anti-EGFR antibody (cetuximab or panitumumab) plus irinotecan. DNA was extracted from peripheral blood. Tag SNPs (single nucleotide polymorphisms) for the two ligands were seleted using Hap Map database (Browser realease #27) and Haploview 4.2 Software following these criteria: MAF (minor allele frecuency) 0.1 and a r2 of 0.8. A total of 11 Tag SNPs were studied: 2 for EREG, and 9 for AREG. Genotype was performed using the BioMarkTM System (Fluidgm). Response rate was evaluated following RECIST criteria 1.1. Results Two polymorphisms in the AREG gene were found to be predictive of response to irinotecan plus anti-EGFR treatment. For the polymorphism g.75422078C > A, overall response rate (partial reponse and stable disease) was 25% for the patients with the A/A genotype, 73% for the C/A genotype and 85% for C/C (p = 0.032). Progression free survival (PFS) was 2.5 months for patients harbouring the A/A genotype compare to 8 months for the patients with A/C and C/C genotypes (p = 0.0001); overall survival was also superior for patients containing the allele C genotypes (5 months for AA and 18 months for C/A and C/C); p = 0.001. For the polymorphism g.75395312G > A, the G/G genotype overall response rate was 100% compare to 69% for the A/G and A/A genotypes (p = 0.048). PFS did not reach statistical significance for this polymorphism. None of the two Tag SNPs for the EREG ligand were found to correlate with response. Conclusions AREG polimorphisms may help to identify refractory mCRC patients who will benefit from irinotecan plus anti-EGFR treatment. Disclosure All authors have declared no conflicts of interest.