Colorectal cancer (CRC) is the third most common cancer worldwide and the leading cause of cancer-related deaths. Recently, several studies have demonstrated that gut microbiota can alter CRC susceptibility and progression by modulating mechanisms such as inflammation and DNA damage, and by producing metabolites involved in tumor progression or suppression. Dysbiosis of gut microbiota has been observed in patients with CRC, with a decrease in commensal bacterial species (butyrate-producing bacteria) and an enrichment of detrimental bacterial populations (pro-inflammatory opportunistic pathogens). CRC is characterized by altered production of bacterial metabolites directly involved in cancer metabolism including short-chain fatty acids and polyamines. Emerging evidence suggests that diet has an important impact on the risk of CRC development. The intake of high-fiber diets and the supplementation of diet with polyunsaturated fatty acids, polyphenols and probiotics, which are known to regulate gut microbiota, could be not only a potential mechanism for the reduction of CRC risk in a primary prevention setting, but may also be important to enhance the response to cancer therapy when used as adjuvant to conventional treatment for CRC. Therefore, a personalized modulation of the pattern of gut microbiome by diet may be a promising approach to prevent the development and progression of CRC and to improve the efficacy of antitumoral therapy.
Obesity is considered an important factor that increases the risk of colorectal cancer (CRC). So far, the association of gut microbiota with both obesity and cancer has been described independently. Nevertheless, a specific obesity-related microbial profile linked to CRC development has not been identified. The aim of this study was to determine the gut microbiota composition in fecal samples from CRC patients with (OB-CRC) and without obesity (L-CRC) compared to the microbiota profile present in non-obese healthy controls (L-HC), in order to unravel the possible relationship between gut microbiota and microbial-derived metabolite trimethylamine N-oxide (TMAO), the inflammatory status, and the intestinal permeability in the context of obesity-associated CRC. The presence of obesity does not induce significant changes in the diversity and richness of intestinal bacteria of CRC patients. Nevertheless, OB-CRC patients display a specific gut microbiota profile characterized by a reduction in butyrate-producing bacteria and an overabundance of opportunistic pathogens, which in turn could be responsible, at least in part, for the higher levels of proinflammatory cytokine IL-1β, the deleterious bacterial metabolite TMAO, and gut permeability found in these patients. These results suggest a possible role of obesity-related gut microbiota in the development of CRC, which could give new clues for the design of new diagnostic tools for CRC prevention.
In metastatic or locally advanced head and neck tumors that present in frail patients or after chemotherapy progression, radiotherapy is normally used as a palliative treatment, with a high rate of symptom palliation and improvement in quality of life. However, there is controversy about what the optimal regimen is. Moreover, despite the poor prognosis of metastatic head and neck cancer, different retrospective studies have shown that a minority of patients with oligometastatic disease experience prolonged disease-free survival after adding curative radiotherapy treatment to the metastatic disease and/or primary tumor. Different retrospective studies have identified clinical prognostic factors that may be used to select candidate patients with metastatic head and neck cancer for a radical approach with radiotherapy. The purpose of this manuscript is to review the role of radiotherapy in metastatic and locally advanced head and neck tumors.
Purpose To identify predictors of palliation for head and neck cancer treated with the “Hypo Trial” hypofractionated radiation therapy regimen in a clinical setting. Design/Method We retrospectively assessed 106 consecutive patients with incurable cancer, treated between January 2008 and December 2018. Regimen used was 30‐36Gy in 5‐6 biweekly fractions of 6Gy. Results The prescription dose was 30Gy in 57 (53.8%) patients and 36Gy in 49 (46.2%) patients. 89.6% patients completed the prescribed treatment. With a median follow‐up of 6.92 months, 79.2% of the patients experienced clinical palliation. Palliation was correlated with the radiation therapy dose (P = 0.05). Median overall and progression‐free survival (OS, PFS) were 7 and 4.63 months, respectively. Achieving palliation was associated to OS (P = 0.01). Conclusions This short palliative hypofractionated scheme resulted in a high rate of palliation, with excellent compliance and acceptable toxicity. Our results show that radiation dose is a predictive factor for palliation.
Emerging evidence has suggested that dysbiosis of the gut microbiota may influence the drug efficacy of colorectal cancer (CRC) patients during cancer treatment by modulating drug metabolism and the host immune response. Moreover, gut microbiota can produce metabolites that may influence tumor proliferation and therapy responsiveness. In this study we have investigated the potential contribution of the gut microbiota and microbial-derived metabolites such as short chain fatty acids and polyamines to neoadjuvant radiochemotherapy (RCT) outcome in CRC patients. First, we established a profile for healthy gut microbiota by comparing the microbial diversity and composition between CRC patients and healthy controls. Second, our metagenomic analysis revealed that the gut microbiota composition of CRC patients was relatively stable over treatment time with neoadjuvant RCT. Nevertheless, treated patients who achieved clinical benefits from RTC (responders, R) had significantly higher microbial diversity and richness compared to non-responder patients (NR). Importantly, the fecal microbiota of the R was enriched in butyrate-producing bacteria and had significantly higher levels of acetic, butyric, isobutyric, and hexanoic acids than NR. In addition, NR patients exhibited higher serum levels of spermine and acetyl polyamines (oncometabolites related to CRC) as well as zonulin (gut permeability marker), and their gut microbiota was abundant in pro-inflammatory species. Finally, we identified a baseline consortium of five bacterial species that could potentially predict CRC treatment outcome. Overall, our results suggest that the gut microbiota may have an important role in the response to cancer therapies in CRC patients.
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