An Integrated Care Approach to Improve Well-Being in Breast Cancer Patients.

BACKGROUND: Breast cancer (BC) treatment has recently been revolutionized by the introduction of newer targeted agents, that helped tailoring therapies around the single patient. Along with increased survival rates, a careful evaluation of diet, lifestyle habits, physical activity, emotional and psychological experiences linked to the treatment journey, is now mandatory. However, a true proposal for an omnicomprehensive and "integrative" approach is still lacking in literature. METHODS: A scientific board of internationally recognized specialists throughout different disciplines designed a shared proposal of holistic approach for BC patients. RESULTS: A narrative review, containing information on BC treatment, endocrinological and diet aspects, physical activity, rehabilitation, integrative medicine, and digital narrative medicine, was developed. CONCLUSIONS: In the context of a patient-centered care, BC treatment cannot be separated from a patient's long-term follow-up and care, and an organized interdisciplinary collaboration is the future in this disease's cure, to make sure that our patients will live longer and better. TRIAL REGISTRATION: NCT05893368: New Model for Integrating Person-based Care (PbC) in the Treatment of Advanced HER2-negative Breast Cancer (PERGIQUAL). Registration date: 29th May 2023.

Clinical Impact of Highly Purified, Whey Proteins in Patients Affected With Colorectal Cancer Undergoing Chemotherapy: Preliminary Results of a Placebo-Controlled Study.

Background and Aims: Sarcopenia, the loss of both lean body and skeletal muscle mass, may interfere in cancer patients outcome. As investigated, whey proteins could prevent the onset of sarcopenia. We have conducted a study to evaluate the effects of whey protein in colorectal cancer patients, undergoing 5-fluorouracil-based chemotherapy. Methods: After written informed consent, patients were blind randomized 1:1 to whey protein (ProLYOtin; arm A) versus placebo (arm B). The patients were assessed both physically and nutritionally before chemotherapy and after 3 (T2) and 6 months (T3) by body impedance assessment, L3-computed tomography scan, Mini Nutritional Assessment (MNA), and Malnutrition Universal Screening Tool (MUST) tests. Results: Forty-seven patients were included in this preliminary analysis. Baseline characteristics were well balanced between the 2 arms. During chemotherapy, 33 patients were reevaluated: anthropometric parameters (lean body mass from 68.5% to 71.2% vs 68.7% to 66.3%, and sarcopenia from 84% to 54% and 83% to 77% from baseline to T2 evaluation in arms A and B, respectively), nutritional status (MNA >24 = 100% [A] vs 73.7% [B]), and toxicity (no adverse effects in 86% [A] vs 29% [B] and 94% [A] vs 29% [B] for hematological and gastrointestinal toxicities, respectively) resulted to be significantly different. At univariate analysis, a condition of malnutrition risk according to MUST (relative risk [RR] = 7.5, P = .02) or MNA (RR = 1.45, P = .02) and ProLYOtin intake (RR = 0.12, P = .01) were found to be significantly predictive of chemotherapy toxicity. Conclusions: At present, our study shows how whey protein could be an important therapeutic option to improve nutritional status, and particularly to prevent severe toxicity during chemotherapy.

Evaluation of 5-fluorouracil degradation rate and Pharmacogenetic profiling to predict toxicity following adjuvant Capecitabine.

BACKGROUND: On account of the lack of predictive biomarkers of toxicity, we investigated whether polymorphisms of genes involved in fluoropyrimidine metabolism and 5-fluorouracil (5-FU) degradation rate were associated with outcomes of adjuvant capecitabine in patients with early stage gastrointestinal cancers. METHODS: Genotyping of DPYD GIVS14A, MTHFR C677T and A1298C SNPs were performed by pyro-sequencing technology. PCR analysis was used for genotyping TYMS-TSER. We also evaluated the 5-FU degradation rate, which determines the amount of drug consumed by PBMC in a time unit. Association of these variables with clinical outcome was evaluated using multivariate logistic regression analysis. RESULTS: One hundred forty-two patients with early stage colon (39%), rectal (28%), stomach (20%) and pancreatic (13%) cancer, treated with adjuvant capecitabine, were included in this retrospective analysis. Seventy and 20% of the patients suffered from at least one G1-4 and G3-4 adverse events, respectively. According to the 5-FU degradation rate, three and 13 patients were assigned as poor (<0.86 ng/mL/106 cells/min) and ultra-rapid (>2.1 ng/mL/106 cells/min) metabolizers, respectively. At a multivariate logistic regression analysis, an altered 5-FU degradation rate (values <0.86 or >2.10 ng/mL/106 cells/min) was associated with grade 3-4 adverse events (OR = 2.09, 95% CI: 1.14-3.82, P = 0.01). No correlation was reported between toxicity and gene polymorphisms except for hand-foot syndrome that was more frequent in the MTHFR 1298CC homozygous variant genotype (OR = 2.03, 95% CI 1.04-3.96, P = 0.03). CONCLUSIONS: 5-FU degradation rate may be regarded as possible predictive biomarker of capecitabine toxicity in early stage gastrointestinal cancer.

5-Fluorouracil degradation rate could predict toxicity in stages II-III colorectal cancer patients undergoing adjuvant FOLFOX.

5-Fluorouracil is commonly used for gastrointestinal cancer treatment in an adjuvant setting; however, the toxicity can lead to a reduction, delay, or discontinuation of treatment. We retrospectively investigated the association between the 5-fluorouracil degradation rate (5-FUDR) and genetic polymorphisms of TSER, DPYD, and MHTFR with toxicity in colorectal cancer patients treated with adjuvant FOLFOX. Pretreatment 5-FUDR and MTHFR A1298T or C677T, TSER, and DPYD gene polymorphisms were characterized in stages II-III colorectal cancer patients. Patients were classified into three metabolic classes according to the 5-FUDR value. Association with toxicities was evaluated retrospectively using logistic regression analysis. Overall, 126 patients were selected (35 women, 91 men). Seven patients were poor metabolizers, 116 patients were normal metabolizers and three patients were ultra-rapid metabolizers. The median 5-FUDR was 1.53 ng/ml/10 cells/min (range: 0.42-2.57 ng/ml/10 cells/min). Severe, rate-limiting toxicities (grades 3-4) were encountered in 22.2% of patients. No associations between MTHFR or TSER polymorphisms and toxicity were detected, whereas 5-FUDR showed a statistically significant association with toxicity (P=0.0047). The DPYD heterozygous mutation was detected in only one patient, who showed grade 4 hematological toxicity and a lower 5-FUDR value. The 5-FUDR value seems not to be affected by MTHFR and TSER polymorphisms. Compared with the available pharmacogenomics tests, the pretreatment evaluation of 5-FUDR increases the proportion of identified colorectal patients at high risk for severe toxicity. Thus, it appears to be a suitable pretreatment toxicity biomarker in a subgroup of patients in whom dose-intensity maintenance is the key factor.

Standard versus limited colon resection for high risk T1 colon cancer. A matched case-control study.

BACKGROUND AND AIMS: The National Comprehensive Cancer Network (NCCN) recommends a colectomy in presence of high risk T1 colon polyps considering the risk of incomplete lymph node dissection or presence of residual disease. We evaluated the outcomes of segmental versus standard colon resection for high risk T1 colon cancers, in order to demonstrate if segmental colectomy (SegCR) allows same short-term and oncological results compared to standard radical colectomy (StaCR). METHODS. A matched case-control study on patients who had undergone segmental versus standard colon resection was performed. One-hundred and two patients with high risk T1 colon cancer after endoscopic polypectomy, divided in 2 homogeneous groups of 51 cases, were analyzed and intra-operative, post-operative and oncological data were compared. RESULTS. Segmental colectomy allowed less operative time and intra-operative blood loss compared to StaCR (p < 0.001). Hospital stay after SegCR was shorter compared to StaCR (p < 0.001). No differences were found in terms of overall morbidity and mortality rates. Five-year actuarial overall, disease-free and disease-specific survival after StaCR were similar to SegCR (87%, 96% and 95% vs. 88%, 97% and 94%, respectively, p = 0.51, p=0.33, p=0.78). CONCLUSIONS. According to our findings, SegCR can be a valid alternative to StaCR for high risk T1 colon polyps. Segmental colectomy allows better peri-operative outcomes compared to StaCR ensuring the same oncological long-term outcomes.