Abstract Background The attitude towards malnutrition varies considerably among oncologists and many malnourished cancer patients receive inadequate nutritional support. Methods Between January and ...July 2015, the Italian Society of Medical Oncology (AIOM) and the Italian Society of Artificial Nutrition and Metabolism (SINPE) conducted a national web-based exploratory survey, to investigate the attitude of oncologists towards malnutrition, and the management of nutritional support, before publication of an inter-society consensus document. Results Of the 2375 AIOM members, 135 (5.7%) participated in the survey, with a satisfactory distribution across all Italian regions. Nutritional assessment and support were routinely integrated into patient care for 38 (28%) responders. According to 66 (49%) participants, nutritional assessment was carried out only upon patients’ request (n=62), or not at all (n=4). Clinical nutritionists were reported to be available by 88 (65%) participants. For 131 responders (97%), nutritional status was decisive (n=63) or often crucial (n=68) in assessing whether anti-cancer treatment was practicable or would be tolerated. Conclusions The low response rate may reflect the lack of awareness and consideration of nutritional issues among Italian oncologists. Although malnutrition and nutritional support seemed to be perceived by the responders as relevant factors for the efficacy of oncologic treatments, it seems that nutritional care practices may well be inappropriate. The lack of collaboration between oncologists and clinical nutritionists may be the first obstacle to overcome. Educational inter-society initiatives aimed at improving nutritional support management for cancer patients in Italy appear urgently needed.
The use of novel targeted anticancer agents has led to overall improvement in the prognosis of many patients affected by various malignancies, but has also been associated with an increased risk of ...poorly characterized toxic effects to different organs, including the kidneys. The high prevalence of kidney impairment in the general population complicates the issue further. Nephrologists most frequently work with patients with cancer when they are asked to investigate kidney function to assess the need for dose adjustments in anticancer therapy. A thorough knowledge of the renal safety profile of novel life-prolonging anticancer therapies, specific features of their metabolism, and pharmacokinetic and pharmacodynamic properties (under normal circumstances as well as in the setting of renal replacement therapy) is, therefore, necessary to preserve kidney function as far as possible and to ensure optimum treatment. In this Review we summarize the present knowledge of renal toxic effects from novel targeted anticancer agents and discuss whether the management of patients' treatment needs to be modified. We also advocate the development of a new onconephrology subspeciality.
Scientific research has often investigated the role of diet as a risk factor for cancer development. It is well known that cancer has a multifactorial origin in which several factors are involved: ...genetic predisposition, dietary factors, personal habits, and infectious and environmental factors. In this Commentary, the role of diet in cancer is discussed following the scientific evidence suggesting that excessive consumption of red meat and processed foods is correlated with a greater risk of contracting cancer. Nevertheless, public health strategies on nutrition in cancer prevention are struggling to take off. The decision to pursue a healthier diet, along with a healthier lifestyle, often comes when the cancer diagnosis is made and not before. On the other hand, scientific evidence demonstrates how nutritional support is increasingly important during oncological treatments. This paper highlights how far we are still from the global adoption of a healthy and sustainable food style from a health, economic, social and environmental perspective. Additionally, it highlights the ancient vision of the role of nutrition on cancer development in which diet is seen only as a possible risk factor, underestimating the protective role in terms of cancer prevention and the modulatory one once the oncological diagnosis has been made.Scientific research has often investigated the role of diet as a risk factor for cancer development. It is well known that cancer has a multifactorial origin in which several factors are involved: genetic predisposition, dietary factors, personal habits, and infectious and environmental factors. In this Commentary, the role of diet in cancer is discussed following the scientific evidence suggesting that excessive consumption of red meat and processed foods is correlated with a greater risk of contracting cancer. Nevertheless, public health strategies on nutrition in cancer prevention are struggling to take off. The decision to pursue a healthier diet, along with a healthier lifestyle, often comes when the cancer diagnosis is made and not before. On the other hand, scientific evidence demonstrates how nutritional support is increasingly important during oncological treatments. This paper highlights how far we are still from the global adoption of a healthy and sustainable food style from a health, economic, social and environmental perspective. Additionally, it highlights the ancient vision of the role of nutrition on cancer development in which diet is seen only as a possible risk factor, underestimating the protective role in terms of cancer prevention and the modulatory one once the oncological diagnosis has been made.
Background:
Knowledge about cancer-related malnutrition and the use of clinical nutrition (CN) in the real-world setting are lacking. We investigated diagnosis and treatment frequency of malnutrition ...in a multinational survey to identify unmet needs in cancer patients’ care.
Methods:
Retrospective analyses were conducted on data from three administrative healthcare datasets from France (n = 570,727), Germany (n = 4642) and Italy (n = 58,468). Data from France described frequency and timing of malnutrition diagnosis in hospitalized gastrointestinal cancer patients. The German data detailed home parenteral nutrition (HPN) use in cancer patients with stage III/IV cancers. The Italian data analysed three cohorts: metastatic with CN, metastatic without CN, and patients without metastatic disease.
Results:
In France, malnutrition diagnosis at first hospitalization occurred in 10% of patients, 13% were subsequently diagnosed, and 77% had no malnutrition diagnosis. In Germany, 16% of patients received HPN. Patients started HPN around 3 months before death. In Italy, 8.4% of metastatic cancer patients received CN; average time between metastasis diagnosis and first CN prescription was 6.6 months. Average time between first CN prescription and death was 3.5 months.
Conclusions:
These data indicate that in the real-world clinical practice, cancer-related malnutrition is under-recognized and undertreated. CN often appears to be prescribed as an end-of-life intervention or is not prescribed at all.
Appropriate CN use remains challenging, and current practice may not allow optimal oncologic outcomes for patients at nutritional risk. Improving awareness of malnutrition and generating further evidence on clinical and economic benefits of CN are critical priorities in oncology.
Despite advances in their diagnosis and treatment, pediatric cancers remain among the leading causes of death in childhood. The development of immunotherapies and other forms of targeted therapies ...has significantly changed the prognosis of some previously incurable cancers in the adult population. However, so far, the results in pediatric cohorts are disappointing, which is mainly due to differences in tumor biology, including extreme heterogeneity and a generally low tumor mutational burden. A central role in the limited efficacy of immunotherapeutic approaches is played by the peculiar characteristics of the tumor microenvironment (TME) in pediatric cancer, with the scarcity of tumor infiltration by T cells and the abundance of stromal cells endowed with lymphocyte suppressor and tumor-growth-promoting activity. Thus, progress in the treatment of pediatric solid tumors will likely be influenced by the ability to modify the TME while delivering novel, more effective therapeutic agents. In this review, we will describe the TME composition in pediatric solid tumors and illustrate recent advances in treatment for the modulation of immune cells belonging to the TME.
The activating natural cytotoxicity receptor NKp30 is critical for natural killer (NK) cell function and tumor immune surveillance. The natural cytotoxicity receptor‐3 (NCR3) gene is transcribed into ...several splice variants whose physiological relevance is still incompletely understood. In this study, we investigated the role of NKp30 and its major ligand B7 homolog 6 (B7‐H6) in patients with hepatocellular carcinoma (HCC). Peripheral blood NK cell phenotype was skewed toward a defective/exhausted immune profile with decreased frequencies of cells expressing NKp30 and natural killer group 2, member D and an increased proportion of cells expressing T‐cell immunoglobulin and mucin‐domain containing‐3. Moreover, NKp30‐positive NK cells had a reduced expression of NCR3 immunostimulatory splice variants and an increased expression of the inhibitory variant in patients with advanced tumor, resulting in deficient NKp30‐mediated functionality. Tumor‐infiltrating lymphocytes showed a prevalent inhibitory NKp30 isoform profile, consistent with decreased NKp30‐mediated function. Of note, there were significant differences in the cytokine milieu between the neoplastic and the surrounding non‐neoplastic tissue, which may have further influenced NKp30 function. Exposure of NK cells to B7‐H6‐expressing HCC cells significantly down‐modulated NKp30, that was prevented by small interfering RNA–mediated knockdown, suggesting a role for this ligand in inhibiting NKp30‐mediated responses. Interestingly, B7‐H6 expression was reduced in HCC tissue and simultaneously augmented as a soluble form in HCC patients, particularly those with advanced staging or larger nodule size. Conclusion: These findings provide evidence in support of a role of NKp30 and its major ligand in HCC development and evolution.
Purpose
CXCR1, one of the receptors for CXCL8, has been identified as a druggable target on breast cancer cancer stem cells (CSC). Reparixin (R), an investigational oral inhibitor of CXCR1, was ...safely administered to metastatic breast cancer patients in combination with paclitaxel (P) and appeared to reduce CSC in a window-of-opportunity trial in operable breast cancer. The fRida trial (NCT02370238) evaluated the addition of R to weekly as first-line therapy for metastatic (m) TNBC.
Subjects and Methods
Subjects with untreated mTNBC were randomized 1:1 to R or placebo days 1–21 in combination with weekly P 80 mg/m
2
on days 1, 8, 15 of 28-day cycles. The primary endpoint was PFS by central review.
Results
123 subjects were randomized (62 to R + P and 61 to placebo + P). PFS was not different between the 2 groups (median 5.5 and 5.6 months for R + P and placebo + P, respectively; HR 1.13,
p
= 0.5996). ALDH
+
and CD24
−
/CD44
+
CSC centrally evaluated by IHC were found in 16 and 34 of the 54 subjects who provided a metastatic tissue biopsy at study entry. Serious adverse events (21.3 and 20% of subjects) and grade ≥ 3 adverse reactions (ADR) (9.1 and 6.3% of all ADRs) occurred at similar frequency in both groups.
Conclusion
fRida is the first randomized, double-blind clinical trial of a CSC-targeting agent in combination with chemotherapy in breast cancer. The primary endpoint of prolonged PFS was not met.
Clinical Trial Registration/Date of Registration
NCT01861054/February 24, 2015.
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