Teresa García

Tumor-infiltrating immune cell profiles and their change after neoadjuvant chemotherapy predict response and prognosis of breast cancer

IntroductionTumor microenvironment immunity is associated with breast cancer outcome. A high lymphocytic infiltration has been associated with response to neoadjuvant chemotherapy, but the contribution to response and prognosis of immune cell subpopulations profiles in both pre-treated and post-treatment residual tumor is still unclear.MethodsWe analyzed pre- and post-treatment tumor-infiltrating immune cells (CD3, CD4, CD8, CD20, CD68, Foxp3) by immunohistochemistry in a series of 121 breast cancer patients homogeneously treated with neoadjuvant chemotherapy. Immune cell profiles were analyzed and correlated with response and survival.ResultsWe identified three tumor-infiltrating immune cell profiles, which were able to predict pathological complete response (pCR) to neoadjuvant chemotherapy (cluster B: 58%, versus clusters A and C: 7%). A higher infiltration by CD4 lymphocytes was the main factor explaining the occurrence of pCR, and this association was validated in six public genomic datasets. A higher chemotherapy effect on lymphocytic infiltration, including an inversion of CD4/CD8 ratio, was associated with pCR and with better prognosis. Analysis of the immune infiltrate in post-chemotherapy residual tumor identified a profile (cluster Y), mainly characterized by high CD3 and CD68 infiltration, with a worse disease free survival.ConclusionsBreast cancer immune cell subpopulation profiles, determined by immunohistochemistry-based computerized analysis, identify groups of patients characterized by high response (in the pre-treatment setting) and poor prognosis (in the post-treatment setting). Further understanding of the mechanisms underlying the distribution of immune cells and their changes after chemotherapy may contribute to the development of new immune-targeted therapies for breast cancer.

Elderly patients with advanced colorectal cancer derive similar benefit without excessive toxicity after first-line chemotherapy with oxaliplatin-based combinations: Comparative outcomes from the 03-TTD-01 phase III study

PURPOSE Healthy elderly patients with metastatic colorectal cancer may benefit from chemotherapy as much as the younger population. This analysis compares the outcomes of first-line oxaliplatin plus fluoropyrimidines in elderly versus young patients. PATIENTS AND METHODS 348 patients were randomized to capecitabine 1000 mg/(m2 12 h), days 1-14 plus oxaliplatin 130 mg/m2 day 1, every 3 weeks or weekly infusional 5-FU 2250 mg/m2 over 48 h plus bimonthly oxaliplatin 85 mg/m2. We evaluated response rate, time to progression, overall survival and toxicity according to age. RESULTS ORR for elderly and young patients were 34.9% and 44.7%, respectively (p=0.081). Median TTP did not differ between the two groups: 8.3 months for patients > or =70 years and 9.6 months for those <70 years (p=0.114). Median OS was 16.8 months and 20.5 months for the > or =70 and <70 years groups, respectively (p=0.74). With XELOX, mild paresthesia and an increase in transaminase levels were more frequent for young patients, whereas grade 3/4 diarrhea was higher in those > or =70 years (25% vs. 8%, p=0.005). For FUOX, only paresthesia was significantly lower in patients > or =70 years (53% vs. 71%, p=0.032). CONCLUSION Elderly patients with MCRC benefit from first-line oxaliplatin-fluoropyrimidine combinations as much as younger patients, without increased toxicity.

Impact of whole-body 18F-FDG PET on diagnostic and therapeutic management of Medical Oncology patients

AIM Most studies evaluating positron-emission tomography (PET) impact on decision making are based on questionnaires sent to referring physicians, with low response rates and potential bias. Studies directly evaluating influence of PET on routine management of Medical Oncology patients are scarce. PATIENTS AND METHODS We retrospectively studied all patients evaluated by whole-body (18)F-FDG PET during 1 year in a Haematology/Oncology Department. We collected information regarding indication, PET results, modification of diagnostic and therapeutic management and adequacy of therapeutic changes. RESULTS One hundred consecutive patients having PET were evaluated. Diagnostic strategy was modified in 63% of patients (30% avoiding biopsy). Therapeutic management was modified by PET in 34% of cases: changes were classified as adequate in 30% and as inadequate in 4% of patients. CONCLUSIONS Our study shows a major impact of PET in the diagnostic and therapeutic management of cancer patients and supports its introduction as a routine diagnostic tool in Medical Oncology.

Nomogram-based prediction of survival in patients with advanced oesophagogastric adenocarcinoma receiving first-line chemotherapy: a multicenter prospective study in the era of trastuzumab

Background:To develop and validate a nomogram and web-based calculator to predict overall survival (OS) in Caucasian-advanced oesophagogastric adenocarcinoma (AOA) patients undergoing first-line combination chemotherapy.Methods:Nine hundred twenty-four AOA patients treated at 28 Spanish teaching hospitals from January 2008 to September 2014 were used as derivation cohort. The result of an adjusted-Cox proportional hazards regression was represented as a nomogram and web-based calculator. The model was validated in 502 prospectively recruited patients treated between October 2014 and December 2016. Harrells c-index was used to evaluate discrimination.Results:The nomogram includes seven predictors associated with OS: HER2-positive tumours treated with trastuzumab, Eastern Cooperative Oncology Group performance status, number of metastatic sites, bone metastases, ascites, histological grade, and neutrophil-to-lymphocyte ratio. Median OS was 5.8 (95% confidence interval (CI), 4.5–6.6), 9.4 (95% CI, 8.5–10.6), and 14 months (95% CI, 11.8–16) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the derivation set and 4.6 (95% CI, 3.3–8.1), 12.7 (95% CI, 11.3–14.3), and 18.3 months (95% CI, 14.6–24.2) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the validation set. The nomogram is well-calibrated and reveals acceptable discriminatory capacity, with optimism-corrected c-indices of 0.618 (95% CI, 0.591–0.631) and 0.673 (95% CI, 0.636–0.709) in derivation and validation groups, respectively. The AGAMENON nomogram outperformed the Royal Marsden Hospital (c-index=0.583; P=0.00046) and Japan Clinical Oncology Group prognostic indices (c-index=0.611; P=0.03351).Conclusions:We developed and validated a straightforward model to predict survival in Caucasian AOA patients initiating first-line polychemotherapy. This model can contribute to inform clinical decision-making and optimise clinical trial design.

Role of Genetic Polymorphisms in NFKB-Mediated Inflammatory Pathways in Response to Primary Chemoradiation Therapy for Rectal Cancer

PURPOSE To investigate whether polymorphisms of genes related to inflammation are associated with pathologic response (primary endpoint) in patients with rectal cancer treated with primary chemoradiation therapy (PCRT). METHODS AND MATERIALS Genomic DNA of 159 patients with locally advanced rectal cancer treated with PCRT was genotyped for polymorphisms rs28362491 (NFKB1), rs1213266/rs5789 (PTGS1), rs5275 (PTGS2), and rs16944/rs1143627 (IL1B) using TaqMan single nucleotide polymorphism genotyping assays. The association between each genotype and pathologic response (poor response vs complete or partial response) was analyzed using logistic regression models. RESULTS The NFKB1 DEL/DEL genotype was associated with pathologic response (odds ratio [OR], 6.39; 95% confidence interval [CI], 0.78-52.65; P=.03) after PCRT. No statistically significant associations between other polymorphisms and response to PCRT were observed. Patients with the NFKB1 DEL/DEL genotype showed a trend for longer disease-free survival (log-rank test, P=.096) and overall survival (P=.049), which was not significant in a multivariate analysis that included pathologic response. Analysis for 6 polymorphisms showed that patients carrying the haplotype rs28362491-DEL/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G (13.7% of cases) had a higher response rate to PCRT (OR, 8.86; 95% CI, 1.21-64.98; P=.034) than the reference group (rs28362491-INS/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G). Clinically significant (grade ≥2) acute organ toxicity was also more frequent in patients with that same haplotype (OR, 4.12; 95% CI, 1.11-15.36; P=.037). CONCLUSIONS Our results suggest that genetic variation in NFKB-related inflammatory pathways might influence sensitivity to primary chemoradiation for rectal cancer. If confirmed, an inflammation-related radiogenetic profile might be used to select patients with rectal cancer for preoperative combined-modality treatment.

The mediating role of spirituality (meaning, peace, faith) between psychological distress and mental adjustment in cancer patients

ObjectiveThe objectives of this study were (a) to determine the psychometric properties of the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp) scale and (b) to provide that FACIT scores behave one-dimensional to establish the mediating role of spiritual well-being in psychological distress and mental adjustment in a sample of patients with non-metastatic, resected cancer.MethodA total of 504 consecutive patients completed the FACIT-Sp, Brief Symptom Inventory, and Mini-Mental Adjustment to Cancer scales. The dimensionality and structure of the scale were assessed by semi-confirmatory factor analysis; the reliability of the derived scale scores was evaluated using the omega coefficient, and regression analysis appraised the FACIT-Sp’s mediating role between psychological distress and mental adjustment.ResultsA clear and theoretically interpretable solution in two factors that agreed generally with solutions reported in other languages was obtained for the FACIT item scores and omega reliabilities of the derived Meaning/Peace (0.85) and Faith (0.86) scales were acceptable. The oblique solution in two factors was compatible with an essentially unidimensional solution of general well-being and associated strongly with psychological distress and mental adjustment. Spiritual well-being acted as a partial mediator between psychological distress and mental adjustment strategies, such as fighting spirit, hope, and cognitive avoidance.ConclusionsThe Spanish version of the FACIT-Sp scale is a reliable and valid clinical evaluation tool, and further highlights the potential clinical implications of spirituality for improving quality of life and adjustment to cancer.

Efficacy and safety of chemotherapy in older versus non-older patients with advanced gastric cancer: A real-world data, non-inferiority analysis.

OBJECTIVE Advanced gastric cancer (AGC) is a common neoplasm in older adults. Nevertheless, there are few specific management data in the literature. The aim of this study was to assess non-inferiority of survival and efficacy-related outcomes of chemotherapy used in older vs non-older patients with AGC. MATERIALS AND METHODS We recruited 1485 patients from the AGAMENON registry of AGC treated with polychemotherapy between 2008-2017. A statistical analysis was conducted to prove non-inferiority for overall survival (OS) associated with the use of chemotherapy schedules in individuals ≥70 vs.<70years. The fixed-margin method was used (hazard ratio [HR]<1.176) that corresponds to conserving at least 85% efficacy. RESULTS 33% (n=489) of the cases analyzed were ≥70 years. Two-agent chemotherapies and combinations with oxaliplatin (48% vs. 29%) were used more often in the older patients, as were modified schedules and/or lower doses. Toxicity grade 3-4 was comparable in both groups, although when looking at any grade, there were more episodes of enteritis, renal toxicity, and fatigue in older patients. In addition, toxicity was a frequent cause for discontinuing treatment in older patients. The response rate was similar in both groups. After adjusting for confounding factors, the non-inferiority of OS associated with schedules administered to the older vs. younger subjects was confirmed: HR 1.02 (90% CI, 0.91-1.14), P (non inferiority)=0.018, as well as progression-free survival: HR 0.97 (90% CI, 0.87-1.08), P(non-inferiority)=0.001. CONCLUSION In this AGC registry, the use of chemotherapy with schedules adapted to patients ≥70 years provided efficacy that was not inferior to that seen in younger cases, with comparable adverse effects.

Influence of clinical and psychological variables on coping strategies and quality of life of cancer patients: NEOCOPING study.

205 Background: NEOCOPING study analyzes the influence of clinicopathological, personal and social variables on coping strategies and quality of life (QoL) in patients with resected tumors at the time of starting adjuvant chemotherapy. METHODS NEOCOPING is a prospective, multicenter, observational study that involves 19 centers and 34 researchers. Applied main questionnaires were: Mini-Mental Adjustment to Cancer (MAC), EORTC QLQ-C30, Brief Symptom Inventory (BSI-18), Shared Decision Making Questionnaire (SDM-Q) patient and doctor, and Multidimensional Scale of Perceived Social Support (MSPSS). RESULTS Table summarizes the characteristics of the first 71 patients enrolled. The most used coping strategies were fighting spirit (X=75.8, SD=25.9) and avoidance (X=64.6, SD=25); most patients were found to have good QoL (X=76.5, SD=16.6). Most did not have psychiatric symptoms, and were pleased with family and social support perceived. Patients were very satisfied with the information received (X=83, SD=19.9), and shared opinions with the doctor (X=90, SD=22.9). QoL was significantly negatively correlated with depression (r=-.688, r=.0001), anxiety (r=.-655, p=.0001), somatization (r=-.638, p=.0001) and hopelessness (r =-.287, p =.033). Depression and somatization predicted 54.8% of the QoL of this sample (F=23,636, p=.0001). CONCLUSIONS Even though patients have a good QoL, adaptative coping strategies and no noticeable psychopathological symptoms at baseline, these symptoms may influence the well-being perception and modulate personal adaptations to the diagnosis and treatment of cancer at a curable stage. [Table: see text].