The role of the nutrition in malnourished cancer patients: Revisiting an old dilemma.

BACKGROUND & AIMS: GLIM definition of malnutrition is recognised all over the world and, when is referring to cancer, it specifies that weight or muscle loss are associated with an inflammatory status. However, the real-world practice shows that GLIM definition cannot encompass all the wide and heterogenous clinical presentations of cancer patients with malnutrition, which involves many other drivers beyond inflammation. Moreover, placing an excessive emphasis on the inflammation can overshadow, in the clinical practice, the role of the nutritional support in malnourished cancer patients. The aim of this paper is not to criticize the rationale of the GLIM definition of cancer cachexia, but to show the complexity and heterogeneity of malnutrition of cancer patients and reasons why nutritional support should deserve such a better consideration among the oncologists. METHODS: Literature pertinent to pathophysiology of malnutrition of cancer patients is scrutinised and reasons for the frequent underuse of nutritional support are critically analysed. RESULTS: The appraisal of the literature shows that there are various pathophysiological patterns of malnutrition among cancer patients and inflammatory markers are not universally present in weight-losing cancer patients. Inflammation alone does not account for weight loss in all cancer patients and factors other than inflammation can drive hypophagia and weight loss, and hypophagia appears to be a primary catalyst for weight loss. Furthermore, malnutrition may be the consequence of the presence of several Nutrition Impact Symptoms or of the oncologic therapy. The nutritional support may fail to show benefits in malnourished cancer patients because the golden standard to validate a therapy relies on RCT, but it is ethically impossible to have an unfed control group of malnourished patients. Furthermore, nutritional interventions often fell short of the optimal standards, adherence to treatment plans was often poor, nutritional support was mainly reserved for very advanced patients and the primary endpoints of the studies on nutritional support were sometimes unrealistic. CONCLUSION: There is a gap between the suggestion of the guidelines which advocate the use of nutritional support to improve the compliance of patients facing intensive oncologic treatments or to prevent an early demise when patients enter a chronic phase of slow nutritional deterioration, and the poor use of nutrition in the real-world practice. This requires a higher level of awareness of the oncologists concerning the reasons for the lacking evidence of efficacy of the nutritional support and an understanding of its potential contribute to improve the outcome of the patients. Finally, this paper calls for a change of the oncologist's approach to the cancer patient, from only focusing on the cure of the tumour to taking care of the patient as a whole.

Age-related and cancer-related sarcopenia: is there a difference?

PURPOSE OF REVIEW: The aim of this review is the attempt to differentiating the pathophysiologic and clinical features of the aging-related sarcopenia from cancer-related sarcopenia. In fact, there is some controversy among the experts mainly regarding two points: is always sarcopenia, even that aging-related one, the expression of a generalized disease or may exist independently and without major alteration of the muscle function? Are always aging-related and cancer-related sarcopenia completely separated entities? RECENT FINDINGS: Literature shows that sarcopenia, defined as simple skeletal muscle mass loss, may range from a mainly focal problem which is common in many healthy elderly people, to a component of a complex multiorgan syndrome as cancer cachexia. Disuse, malnutrition and (neuro)degenerative processes can account for most of the aging-related sarcopenias while systemic inflammation and secretion of cancer-and immune-related molecules play an additional major role in cachexia. SUMMARY: A multimodal approach including physical exercise and optimized nutritional support are the key measures to offset sarcopenia with some contribution by the anti-inflammatory drugs in cancer patients. Results are more promising in elderly patients and are still pending for cancer patients where a more specific approach will only rely on the identification and contrast of the key mediators of the cachectic process.

Evolving concepts on perioperative nutrition of sarcopenic cancer patients.

The recent recognition of the association of sarcopenia with an increased risk of complications after a surgical procedure calls for rethinking the proper approach of the perioperative care in cancer patients. Sarcopenia is broadly considered in literature according to three different definitions: loss of muscle mass, loss of muscle mass plus reduced muscle function and myosteatosis. The aim of this short review on this issue is to define the excess of risk by type of primary and of surgical procedure, depending on the definition of sarcopenia, to speculate on this association (casual versus causal) and to examine the current therapeutical approaches. The analysis of the data shows that sarcopenia, defined as loss of muscle mass plus reduced muscle function, has the higher predictive power for the occurrence of postoperative complications than the two other definitions, and any definition of sarcopenia works better than the usual indexes or scores of surgical risk. Our analysis supports the concept that: a) sarcopenia is frequently associated with inflammation, but inflammation cannot be considered the only or the absolute cause for sarcopenia, b) sarcopenia is not a simple marker of risk but can have a direct role in the increase of risk. Data on perioperative care of sarcopenic cancer patients are scanty but a correct approach cannot rely on nutritional support alone but on a combined approach of optimized nutrition and exercise, hopefully associated with an anti-inflammatory treatment. This strategy should be applied proactively in keeping with the recent recommendations of the American Society of Clinical Oncology for the medical treatment of advanced cancer patients even if a clear demonstration of effectiveness is still lacking.

Supplemental parenteral nutrition in cancer care: why, who, when.

Malnutrition is an often-overlooked challenge for patients with cancer. It is associated with muscle mass reduction, poor compliance and response to cancer treatments, decreased quality of life, and reduced survival time. The nutritional assessment and intervention should be a vital part of any comprehensive cancer treatment plan. However, data on artificial nutrition supplied based on caloric needs during cancer care are scarce. In this review, we discuss the recommendations of the European and American societies for clinical nutrition on the use of nutritional interventions in malnourished patients with cancer in the context of current clinical practice. In particular, when enteral nutrition (oral or tube feeding) is not feasible or fails to meet the complete nutritional needs, supplemental parenteral nutrition (SPN) can bridge the gap. We report the available evidence on SPN in cancer patients and identify the perceived barriers to the wider application of this intervention. Finally, we suggest a 'permissive' role of SPN in cancer care but highlight the need for rigorous clinical studies to further evaluate the use of SPN in different populations of cancer patients.

Survival of the starving cancer patient: a food for thought for oncologists.

Patients with untreated malignant bowel obstruction usually survive less than 1 month and death is accounted by 3 components: the tumour, the obstruction and the starvation. The potential benefit of total parenteral nutrition cannot be investigated, for ethical reasons, through RCT which would include a non-fed control arm. We hypothesized that if literature would consistently confirm that untreated malignant small bowel obstruction patients survive less than 1 month, there would be no need of randomised clinical trial to study the effect of total parenteral nutrition in these patients and such approach could potentially become part of the armamentarium of the oncologist. We reviewed the last 40 years of the literature on patients with malignant small bowel obstruction receiving a palliative care and distinguished 3 groups: Group I (20 studies), patients with untreated tumour, obstruction and starvation; Group II (27 studies), patients with treatment of the obstruction only, and Group III (25 studies), patients with total parenteral nutrition and some control of the obstruction. Median survivals were about 1, 1.5 and > 3 months in the 3 groups, respectively. Data suggest that total parenteral nutrition might benefit these patients being associated with a longer survival and sometimes allowing for further oncologic therapies. In conclusion, a timely intervention through parenteral nutrition should have a priority indication in a selected group of patients with malignant bowel obstruction before the occurrence of an irreversible nutritional deterioration, This would allow patients with spontaneous remission to survive longer or to be occasionally candidate for further oncologic therapies.

Calorie restriction in cancer patients undergoing chemotherapy: Facts, phantasy or misunderstanding.

BACKGROUND & AIMS: Experimental studies in cancer cell lines and tumour-bearing animals support the concept that a short-period fasting could potentiate the effect of antineoplastic chemotherapy due to a particular metabolic adaptation normal cells whereas cancer cells would remain particularly sensitive to the toxic effects of the therapy. The potential of such approach is actually emphasized by the media but data in humans are very scant and many oncologists fear that peri-chemotherapy fasting might worsen the patient nutritional status. The aim of this review is to focus on the benefits versus the adverse effects of the peri-chemotherapy fasting and to clarify if discrepancy of opinions regarding this approach relies on data from clinical trials or simply on misunderstandings or prejudices. METHODS: We reviewed all the available literature regarding the peri-chemotherapy fasting in cancer patients with a special focus on compliance, adverse event prevalence and tumour response. RESULTS: Seven papers were available for the analysis. All studies included seemingly well-nourished patients and most of them had a breast or a gynaecologic cancer. Almost all concluded for the feasibility of the peri-chemotherapy fasting, with a good patient compliance. Weight loss was always reported but it was generally mild even if sometimes required a nutritional intervention between the cycles of chemotherapy. One RCT reported a better radiological response of the breast cancer at the neoadjuvant chemotherapy. CONCLUSION: Peri-chemotherapy fasting appears a safe procedure in well-nourished patients receiving a short-term chemotherapy. However claims of oncologic benefit are premature and rumors about its efficacy are presently unjustified.

Home parenteral nutrition versus artificial hydration in malnourished patients with cancer in palliative care: a prospective, cohort survival study.

OBJECTIVE: The evidence base for home parenteral nutrition (HPN) in patients with advanced cancer is lacking. To compare the survival of malnourished patients with cancer undergoing palliative care who received HPN with a homogeneous group of patients, equally eligible for HPN, who did not receive HPN. DESIGN: Prospective, cohort study; tertiary university hospital, home care, hospice. METHODS: Patients were assessed for HPN eligibility according to the guidelines. In the eligible population, who received both HPN and chemotherapy was excluded, while who received only HPN was included in the HPN+ group and who received neither HPN nor chemotherapy but artificial hydration (AH) was included in the HPN- group. RESULTS: 301 patients were assessed for HPN eligibility and 86 patients (28.6%) were excluded for having severe organ dysfunction or Karnofsky performance status <50. In outcome analysis, 90 patients (29.9%) were excluded for receiving both HPN and chemotherapy, while 125 (41.5%) were included, 89 in HPN+ group (29.5%) and 36 in HPN- group (12%). The survival of the two groups showed a significant difference favouring patients receiving HPN (median overall survival: 4.3 vs 1.5 months, p<0.001). The multivariate analysis of the risk factors for mortality showed that not receiving HPN accounted for the strongest one (HR 25.72, 95% CI 13·65 to 48.44). CONCLUSIONS: Comparative survival associated with the use of HPN versus AH showed significantly longer survival in malnourished patients with advanced cancer receiving HPN. These data support the guideline recommendation that HPN should be considered when malnutrition represents the overriding threat for the survival of these patients.

A European survey on the practice of nutritional interventions in head-neck cancer patients undergoing curative treatment with radio(chemo)therapy.

PURPOSE: As the practice of nutritional support in patients with head and neck cancer (HNC) during curative radio(chemo)therapy is quite heterogeneous, we carried out a survey among European specialists. METHODS: A 19-item questionnaire was drawn up and disseminated via the web by European scientific societies involved in HNC and nutrition. RESULTS: Among 220 responses, the first choice was always for the enteral route; naso-enteral tube feeding was preferred to gastrostomy in the short term, while the opposite for period longer than 1 month. Indications were not solely related to the patient's nutritional status, but also to the potential burden of the therapy. CONCLUSION: European HNC specialists contextualize the use of the nutritional support in a comprehensive plan of therapy. There is still uncertainty relating to the role of naso-enteral feeding versus gastrostomy feeding in patients requiring < 1 month nutritional support, an issue that should be further investigated.

Diagnostic criteria for cancer cachexia: reduced food intake and inflammation predict weight loss and survival in an international, multi-cohort analysis.

BACKGROUND: Cancer-associated weight loss (WL) associates with increased mortality. International consensus suggests that WL is driven by a variable combination of reduced food intake and/or altered metabolism, the latter often represented by the inflammatory biomarker C-reactive protein (CRP). We aggregated data from Canadian and European research studies to evaluate the associations of reduced food intake and CRP with cancer-associated WL (primary endpoint) and overall survival (OS, secondary endpoint). METHODS: The data set included a total of 12,253 patients at risk for cancer-associated WL. Patient-reported WL history (% in 6 months) and food intake (normal, moderately, or severely reduced) were measured in all patients; CRP (mg/L) and OS were measured in N = 4960 and N = 9952 patients, respectively. All measures were from a baseline assessment. Clinical variables potentially associated with WL and overall survival (OS) including age, sex, cancer diagnosis, disease stage, and performance status were evaluated using multinomial logistic regression MLR and Cox proportional hazards models, respectively. RESULTS: Patients had a mean weight change of -7.3% (±7.1), which was categorized as: ±2.4% (stable weight; 30.4%), 2.5-5.9% (19.7%), 6.0-10.0% (23.2%), 11.0-14.9% (12.0%), ≥15.0% (14.6%). Normal food intake, moderately, and severely reduced food intake occurred in 37.9%, 42.8%, and 19.4%, respectively. In MLR, severe WL (≥15%) (vs. stable weight) was more likely (P < 0.0001) if food intake was moderately [OR 6.28, 95% confidence interval (CI 5.28-7.47)] or severely reduced [OR 18.98 (95% CI 15.30-23.56)]. In subset analysis, adjusted for food intake, CRP was independently associated (P < 0.0001) with ≥15% WL [CRP 10-100 mg/L: OR 2.00, (95% CI 1.58-2.53)] and [CRP > 100 mg/L: OR 2.30 (95% CI 1.62-3.26)]. Diagnosis, stage, and performance status, but not age or sex, were significantly associated with WL. Median OS was 9.9 months (95% CI 9.5-10.3), with median follow-up of 39.7 months (95% CI 38.8-40.6). Moderately and severely reduced food intake and CRP independently predicted OS (P < 0.0001). CONCLUSIONS: Modelling WL as the dependent variable is an approach that can help to identify clinical features and biomarkers associated with WL. Here, we identify criterion values for food intake impairment and CRP that may improve the diagnosis and classification of cancer-associated cachexia.

Does nutrition support during chemotherapy increase long-term survival of cancer patients? Lessons from the past and future perspectives.

PURPOSE: The aim of this review was to analyze the potential effect of the nutritional support (oral supplementation/counseling, tube feeding, parenteral nutrition) combined with chemotherapy on long-term survival of cancer patients. METHODS: Using various electronic databases, we retrieved all English language papers on the combination nutritional support and chemotherapy and including data on long-term survival. RESULTS: 29 trials (4 non-RCT) were retrieved. No significant benefit was observed except for a longer survival in a few selected subgroups of patients, depending on the tumor stage and compliance with the nutritional support. However, no study included survival as primary endpoint or was adequately powered for this purpose, and patients were seldom affected by malnutrition, a condition which would have made them extremely vulnerable and unsafe during an intensive chemotherapy with significant gastrointestinal toxicity. Finally, nutritional regimens were often inappropriate as regards quality and quantity of nutrients or too similar in the two arms of the trial to expect a result. CONCLUSION: From the review of these trials, it appears clear that there is absence of evidence more than evidence of absence of effect of the supplemental nutritional support. This poor scenario should not discourage future large multicenter trials to assess the potential of an early versus a delayed support in mildly malnourished patients. From the practical point of view, a nutritional supplementation should be considered when severe malnutrition caused by the disease or following repeated oncologic treatments can make the patients poorly compliant with further chemotherapy cycles, as recommended by the international guidelines.

ESPEN practical guideline: Clinical Nutrition in cancer.

BACKGROUND: This practical guideline is based on the current scientific ESPEN guidelines on nutrition in cancer patients. METHODS: ESPEN guidelines have been shortened and transformed into flow charts for easier use in clinical practice. The practical guideline is dedicated to all professionals including physicians, dieticians, nutritionists and nurses working with patients with cancer. RESULTS: A total of 43 recommendations are presented with short commentaries for the nutritional and metabolic management of patients with neoplastic diseases. The disease-related recommendations are preceded by general recommendations on the diagnostics of nutritional status in cancer patients. CONCLUSION: This practical guideline gives guidance to health care providers involved in the management of cancer patients to offer optimal nutritional care.

Nutrition Information in Oncology - Extending the Electronic Patient-Record Data Set.

Electronic health records (EHRs) present extensive patient information and may be used as a tool to improve health care. However, the oncology context presents a complex content that increases the difficulties of EHR application. This study aimed at developing openEHR-archetypes representing clinical concepts in cancer nutrition-care, as well as to develop an openEHR-template including the aforementioned archetypes. The study involved the following stages: 1) a thorough literature review, followed by an expert's (nutrition guideline authors) survey, aiming to identify the main statements of published clinical guidelines on nutrition in cancer patients that were not included on the Clinical Knowledge Manager (CKM) repository; 2) modelling of the archetypes using the Ocean Archetype Software and submission to the CKM repository; 3) creating an example template with Template Designer; and 4) automatic conversion of the openEHR-template into a readily usable EHR using VCIntegrator. The clinical concepts (among 17 clinical concepts not yet available in the CKM repository) chosen for further development were: body composition, diet plan, dietary nutrients, dietary supplements, dietary intake assessment, and Malnutrition Screening Tool (MST). So far, four archetypes were accepted for review in the CKM repository and a template was created and converted into an EHR. This study designed new openEHR-archetypes for nutrition management in cancer patients. These archetypes can be included in EHR. Future studies are needed to assess their applicability in other areas and their practical impact on data quality, system interoperability and, ultimately, on clinical practice and research.

Nutritional Status in Patients with Esophageal Cancer Receiving Chemoradiation and Assessing the Efficacy of Usual Care for Nutritional Managements.

BACKGROUND: Malnutrition is prevalent in esophageal cancer patients which affects cancer prognosis. The purpose of this study was a comprehensive assessment of nutritional status during Chemoradiation (CRT). METHODS: Newly diagnosed adults with esophageal cancer were recruited for this study. Patient-Generated- Subjective Global Assessment (PG-SGA), anthropometric indices, body composition, dietary intake, laboratory tests, and nutritional-related complications were assessed before, after, and 4 to 6 weeks after CRT. RESULTS: Seventy-one cases were enrolled. The mean age was 66.8±12 years. Patients' mean weight loss was 2.42±2.4 kilograms during treatment. A significant reduction observed in mean MUAC (26.68±4.9 vs. 25.42±5.1 cm), fat mass percentage (24.11±11.8 vs. 22.8±12.5), fat free mass index (16.87±2.4 vs. 16.47±2.6 kg/m2) and hand grip strength (43.2±19 vs. 36.1±20 kg) during CRT (all p-values <0.0001). We had also a non-significant change in mean energy intake (19.5±11 vs. 18.3±11 kcal/kgw. day) and protein intake (0.56±0.4 vs. 0.66±0.5 g/kgw.day) during CRT.  In our assessment before, immediately after and 4-6 weeks following CRT, we recorded energy intake insufficiency in 55.7%, 58.7% and 27.3% and protein intake inadequacy in 89.8%, 89.1% and 72.7% of cases, respectively. The most common complications were dysphagia (56.7%), anorexia (25%), and constipation (47.9%) at admission. Dysphagia improved in some cases (42%), but anorexia (35%), early satiety (25%), Esophagitis (25%), dysosmia (21%) and dysgeusia (17%) were increased as CRT complication. yet, 25% of patients had dysphagia and 34.4% had constipation 4-6 weeks after CRT. The twelve-months mortality was significantly associated with lower BMI after CRT, primary PG-SGA score, weight loss, BMI<18.5, MUAC, physical performance, living in rural or urban areas, addiction. CONCLUSION: Our study demonstrated a high prevalence of malnutrition among esophageal cancer patients which worsened during Chemoradiotherapy. Our findings warrant early screening and monitoring of nutritional status and effective nutritional interventions with symptoms management during treatment in these patients.
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Monitoring Response to Home Parenteral Nutrition in Adult Cancer Patients.

Current guidelines recommend home parenteral nutrition (HPN) for cancer patients with chronic deficiencies of dietary intake or absorption when enteral nutrition is not adequate or feasible in suitable patients. HPN has been shown to slow down progressive weight loss and improve nutritional status, but limited information is available on the monitoring practice of cancer patients on HPN. Clinical management of these patients based only on nutritional status is incomplete. Moreover, some commonly used clinical parameters to monitor patients (weight loss, body weight, body mass index, and oral food intake) do not accurately reflect patient's body composition, while bioelectrical impedance analysis (BIA) is a validated tool to properly assess nutritional status on a regular basis. Therefore, patient's monitoring should rely on other affordable indicators such as Karnofsky Performance Status (KPS) and modified Glasgow Prognostic Score (mGPS) to also assess patient's functional status and prognosis. Finally, catheter-related complications and quality of life represent crucial issues to be monitored over time. The purpose of this narrative review is to describe the role and relevance of monitoring cancer patients on HPN, regardless of whether they are receiving anticancer treatments. These practical tips may be clinically useful to better guide healthcare providers in the nutritional care of these patients.