Nutritional deterioration is so frequently encountered in cancer patients and is often accepted as a part of the disease and its treatment [27, 28]. The purpose of nutritional assessment in cancer patients is to discover mild or moderate malnutrition before the patients become overtly wasted in order to prevent further deterioration and improve their quality of care. Conventionally, nutritional status assessed by anthropometric measurement and laboratory assessment [29]. However, in clinical settings, some of the anthropometric measurements and laboratory assessments are not ideal because they are neither accurate nor convenient [30].
Hence, the current study strongly aimed to evaluate the nutritional status of cancer patients at the baseline before the initiation of the first cycle of chemotherapy and after the completion of chemotherapy regimen using SGA and anthropometric measurements (Height, Weight, BMI, TSF, MAC and MAMC). In this study, SGA showed that the majority (80.3%) of patients enrolled in the study were malnourished after the completion of chemotherapy regimen, of which 41.0% were severely malnourished and 39.3% were moderately or suspected of being malnourished. In comparison, 36.0% of patients were malnourished at the baseline before the initiation of the first cycle of chemotherapy, of which 15.6% were severely malnourished and 20.3% were moderately or suspected of being malnourished. The difference between the proportions of SGA categories at the baseline and after the completion of chemotherapy regimen was statistically significant (p < 0.001). These findings are not unexpected as patients with cancer have the highest incidence of malnutrition (40%-80%) amongst hospital inpatients [31]. Cancer patients are especially at risk for malnutrition since they have elevated metabolic requirements due to tumor burden, poor or insufficient oral intake due to chemotherapy induced emesis and inherently altered taste and smell [32, 33].
As far as we are aware, various nutritional methods have been used to assess the nutritional status of patients with cancer and under various conditions (specific type of cancer, postoperative, both before and after surgery, prior to chemotherapy) [16, 28, 30, 34, 35, 36, 37]. However, there is no study in the literature assessing the nutritional status of patients with various types of cancer at the baseline before the initiation of the first cycle of chemotherapy and after the completion of chemotherapy regimen, making it difficult to compare our findings with findings of different studies.
A cross-sectional study conducted by Montoya et al. on 88 cancer patients admitted for chemotherapy to determine the overall prevalence of malnutrition using SGA reported that approximately half (47.6%) of cancer patients admitted for chemotherapy were malnourished or at a high risk for further deterioration of nutritional status [37]. Another a cross-sectional study assessing the risk of malnutrition and nutritional status of 65 hospitalized patients with cancer (lymphoma, breast, prostate, oesophagus, lung, sarcoma and myeloma) using SGA reported that 75% of patients were malnourished [16, 34]. Wu and Yin et al.’s study conducted to investigate the role of SGA in nutritional assessment among patients with gastrointestinal cancer revealed that the prevalence of malnutrition among patients was 48.2% [30]. A retrospective clinical epidemiologic study conducted by Gupta and his colleagues among 234 colorectal cancer patients aged 29–82 years to evaluate the prognostic significance of SGA in advanced colorectal cancer reported that the prevalence of malnutrition was 52% [35]. Furthermore, Ryu and his colleagues reported that the prevalence of malnutrition among gastric cancer patients using SGA was 31% at admission prior to surgery and 80% at 6 months after surgery [28].
Weight loss is common in cancer patients and is often a symptom already present at diagnosis. Weight loss is an independent predictor of survival in patients with cancer, and it has been associated with poorer physical function, increased psychological distress and reduced quality of life [38]. In current study, a significant difference in mean body weight between at the baseline and after the completion of chemotherapy regimen was observed, the mean body weight of patients reduced significantly after the completion of chemotherapy regimen (71.62 kg at the baseline→ 66.13 kg after the completion of chemotherapy regimen, p < 0.001). In concordance with our results, a prospective study conducted among 30 cancer patients of various sites (cervix, breast, stomach, ovary, thyroid, esophagus and larynx) between 30 and 70 years of age and scheduled for first cycle of chemotherapy to determine the nutritional status of patients receiving chemotherapy before the initiation of chemotherapy and on the third week after the first cycle of chemotherapy found that 90% of patients suffered from weight loss 3 weeks after the first cycle of chemotherapy, irrespective of the type of cancer [39].
Bincy and his colleagues in their study reported that the mean weight reduced 3weeks after the first cycle of chemotherapy (55.96 kg before chemotherapy→54.36 kg 3weeks after 1st cycle of chemotherapy), but these changes in weight were not statistically significant (Bincy and Chacko, 2014). In Bincy et al.’s study [39], no statistically significant difference in mean body weight between before chemotherapy and 3 weeks after the first cycle of chemotherapy may be due to that the nutritional assessment was carried out on the third week after the first cycle of chemotherapy and not after the completion of all scheduled cycles of chemotherapy regimen.
The findings of this study revealed a significant reduction in the mean height of patients between at the baseline and after the completion of chemotherapy regimen (163.57 cm→162.60 cm after the completion of chemotherapy regimen, p = 0.007). In fact, a reduction in the mean height of patients after the completion of chemotherapy is due to evident deformities in the spinal cord of patients (e.g., kyphosis). This means that our height measurements after the completion of chemotherapy were inaccurate.
In terms of BMI of the patients, 54% of patients were obese or overweight at the baseline before the initiation of the first cycle of chemotherapy in comparison to 46.6% were obese or overweight after the completion of chemotherapy regimen. In 2016, an estimated 1.97 billion adults and over 338 million children and adolescents were overweight or obese globally [40]; this is related to the individual choices of diet, lifestyle and physical activity, which can be controlled to some extent; an obesogenic environment of sociocultural, economic and marketing challenges to the achievement of healthy ways of life [41]; low cost, widely available energy-dense food and drink, combined with few opportunities to easily engage in physical activity, stacking the odds against successful weight management for the majority of the population [42]. The WCRF/AICR in the third expert report, “Diet, Nutrition, Physical Activity and Cancer: a Global Perspective” showed that being overweight or obese is a cause of 12 cancers. There is convincing evidence that greater body fatness is a cause of cancers of the oesophagus, pancreas, liver, colorectal, endometrial, breast (postmenopausal) and kidney. Greater body fatness is also probably a cause of cancers of the mouth, pharynx and larynx, stomach, gallbladder, ovary and prostate (advanced) [43]. Accordingly, the WCRF/AICR recommended to keep weight within the healthy range (BMI of 18.5-24-9 kg/m2) and avoid weight gain in adult life [43].
In this study, a significant difference in mean BMI between at the baseline and after the completion of chemotherapy regimen was observed, the mean BMI reduced significantly after the completion of chemotherapy regimen (26.82 kg/m2 at the baseline→25.06 kg/m2 after the completion of chemotherapy regimen, p < 0.001). Similarly, Bincy and his colleagues reported a significant difference in mean BMI of patients between before chemotherapy and 3 weeks after the first cycle of chemotherapy (23.17 kg/m2 before chemotherpay→22.54 kg/m2 3weeks after the 1st cycle of chemotherapy, p < 0.01) [39].
Other notable findings, the current study reported a significant difference in mean TSF, MAC and MAMC between at the baseline before the initiation of the first cycle of chemotherapy and after the completion of chemotherapy regimen. TSF, an established measure of fat stores. In this study, the mean TSF reduced significantly after the completion of chemotherapy regimen (18.71 mm at the baseline→14.89 mm after the completion of chemotherapy regimen, p < 0.001), pointing to evidence of subcutaneous fat loss among cancer patients. MAMC is a good indicator of muscle mass and can be used as a proxy of wasting. MAMC is an early indicator of nutritional depletion, provides an estimate of somatic protein reserve and may be a valuable auxiliary tool for prognosis as an indicator of proteolysis and cachexia [44]. Furthermore, MAMC is a significant predicator of all-cause mortality [45], physical performance and function, quality of life (QoL) and mental health [46, 47, 48]. The current study reported a significant difference in MAMC between at the baseline and after the completion of chemotherapy regimen (23.24 cm at the baseline→21.96 cm after the completion of chemotherapy regimen, p < 0.001), highlighting to evidence of nutritional depletion and muscle wasting among cancer patients. In line with our findings, Bincy and his colleagues also found a significant decrease in mean TSF, MAC and MAMC between before chemotherapy and 3 weeks after the first cycle of chemotherapy (14.54 mm vs 14.41 mm, 27.46 cm vs 27.27 cm and 22.90 cm vs 22.76 cm, respectively), p < 0.01 [39].
In this a prospective study evaluating the nutritional status of 64 adult newly diagnosed cancer patients at the baseline before commencing the first cycle of chemotherapy and after the completion of chemotherapy regimen, an interesting observation was that, although the mean BMI was within the normal range, a high prevalence of malnutrition was detected using SGA. BMI and SGA are not concordant, reflecting the limitations of markers of nutritional status. While with SGA malnutrition was detected in patients with normal to high BMI, with BMI normal and/or overnutrition (BMI > 18.5 kg/m2) was diagnosed. At a time, thirty-six percent of patients at the baseline were malnourished or at risk of malnutrition using SGA, 7.9% of the same patients were underweight and/or malnourished using BMI (BMI < 18.5 kg/m2). Similarly, after the completion of chemotherapy regimen, 80% of the same patients were malnourished or at high risk of malnutrition using SGA, whilst 10.3% were underweight and/or malnourished using BMI. This means that malnutrition can be masked by excessive adiposity, SGA can detect malnutrition even among overweight or obese subjects and before BMI drops below 18.5–24.9 kg/m2 and thus using BMI alone is not sufficient to detect malnutrition.
Moreover, in the current study, an important issue deserved greater attention is that, weight was not measured for cancer patients with edema and ascites. Ascites and edema in cancer patients may also mask weight loss; it may even result in weight gain. Additionally, for some cancer patients with poor QoL, critically ill and spend most of their time in bed or totally bedridden, anthropometry (Height, Weight, BMI, TSF, MAC and MAMC) were impossible to measured.
In this a prospective study 45 patients out of a total 64 patients were evaluated at the baseline (pre) and after the completion of chemotherapy regimen (post) for vitamin B12, HoloTC, vitamin B6 and folate as well as vitamin B12- related metabolites MMA and Hcy. Our results reported a significant difference in serum vitamin B12, MMA and Hcy concentrations between at the baseline and after the completion of chemotherapy regimen. Serum vitamin B12 concentration reduced significantly after the completion of chemotherapy regimen, whilst vitamin B12- related metabolites MMA and Hcy significantly elevated after the completion of chemotherapy regimen. Based on these results, our study asserts the presence of functional vitamin B12 deficiency among cancer patients. It is important to note that MMA is clearly more specific to vitamin B12 deficiency compared to Hcy. A deficiency of vitamin B12 at the tissue level can lead to elevation of both MMA and Hcy even when serum vitamin B12 concentrations are within the reference range [49]. Meanwhile, inadequate levels of folate, vitamin B12, vitamin B6, and riboflavin may all result in high levels of homocysteine [50, 51].
Consistent with our study, Vashi et al.’s a cross sectional study conducted among cancer patients to evaluate the prevalence of vitamin B12 deficiency using serum vitamin B12, MMA and Hcy [52]. Vashi et al. found that the prevalence of vitamin B12 deficiency was 8.9% using a cut off point for vitamin B12 deficiency < 300 pg/ml, whilst using MMA and Hcy levels, the respective prevalence rates were 10.8% and 17.4%, respectively, suggesting that using serum vitamin B12 testing alone can lead to an under diagnosis of vitamin B12 deficiency by up to 16% [52]. Additionally, Vashi et al. suggested MMA to have the best discriminatory power in predicting vitamin B12 deficiency, such as 8.5% of a total sample classified as B12 deficient based on MMA but vitamin B12 sufficient based on serum vitamin B12. The prevalence of vitamin B12 deficiency, using serum MMA in conjugation with serum B12 was 17.4% versus 8.9% using serum vitamin B12 alone [52].
Similarly, in a retrospective study of 241 cancer patients with advanced malignancy performed by Solomon and his colleagues, MMA, Hcy and B12 were measured in 240(99%), 191(79%) and 225(93%) of these 241 cancer patients, respectively [53]. Solomon et al. reveled that B12 levels were low (≤ 300 pg/ml) in 17% and high (> 900 pg/ml) in 30% (of them 16% with B12 values ≥ 1500 pg/ml) of tested patients. MMA and Hcy values were elevated in 38% and 23% of tested patients, respectively [53]. It is also of note that both metabolites (MMA and Hcy) were elevated along together in only 23% of patients among them both metabolites were measured, while isolated elevations of MMA (in 55% of patients) were significantly more frequent than isolated elevations in Hcy (in 22% of patients), p < 0.001 [53]. Solomon et al. also reported that elevation of MMA and/or Hcy values, consistent with functional vitamin B12 deficiency, occurred in more than half of patients studied even when B12 values were markedly elevated (≥ 1500 pg/ml) [53].
Our findings of a significant difference in serum HoloTC, vitamin B6 and folate concentrations between at the baseline and after the completion of chemotherapy regimen is in agreement with a clinical study of a single breast cancer patient [54], which found a pronounced HoloTC deficiency after completion of full chemotherapy regimen (107 pmol/l at the baseline→29 pmol/l after the completion of chemotherapy regimen, reference range > 35 pmol/l). Similarly, in this a clinical study of a single breast cancer patient by schloss and his colleague’s, vitamin B6 and folate reduced after the completion of chemotherapy regimen, but not less than the reference range [54].
The present study showed that serum albumin concentration reduced significantly after the completion of chemotherapy regimen, and this is a matter of great health concern given an increased risk of malnutrition, inflammation, mortality, as well as increased risk of chemotherapy toxicity and early termination of chemotherapy. Consistent with our findings, a prospective study conducted among 30 newly diagnosed patients of various sites by Bincy et al. reported that all patients had a reduction in serum albumin level before and 3weeks after chemotherapy, but remained within normal range [39]. Another study by Usharani et al. reported a significant decrease in albumin before chemotherapy and 3 weeks after chemotherapy [55].
In this prospective study, considering 64 adult newly diagnosed cancer patients, there is a significant difference Hb and HCT values between at the baseline before the initiation of the first cycle of chemotherapy and after the completion of chemotherapy regimen. The results reported drastic reduction in Hb and HCT values after the completion of chemotherapy regimen (12.0→9.6 g/dL, p < 0.001), (4.40→3.27×106/L, p < 0.001) and (35.28→29.15%), respectively. The present study, based on its findings, suggests cancer-related anemia. Anemia is the most frequently encountered hematologic abnormality in cancer patients and even more frequent in cancer patients receiving myelosuppressive chemotherapy, radiation therapy or both [56]. The incidence and severity of anemia, varies significantly [57, 58, 59], depend on the type and extent of the malignancy; the type, schedule, and intensity of cancer therapy. It is also may be a result of nutritional deficiencies, bleeding, hemolysis, marrow infiltration by tumor, and/or inflammatory cytokines associated with chronic disease [56, 60]. Similar to our results, Bincy et al.’s a prospective study showed significant decrease in hemoglobin levels (p < 0.01) before and 3weeks after the first cycle of chemotherapy [39].
Another noteworthy finding, a significant difference in red cell indices (MCV and MCH) values. Our results showed that MCV and MCH values significantly elevated after the completion of chemotherapy regimen (81.6→93.7 fL, p < 0.001) and (27.2→30.2 Pg, p < 0.001), respectively, suggesting the development of macrocytic anemia among cancer patients after the completion of chemotherapy regimen. Ideally, elevation of MMA, a best indicator of functional vitamin B12 deficiency, accompanied by a reduction in Hb and HCT values and elevation in MCV and MCH values, consistent with functional vitamin B12 deficiency related anemia among cancer patients after the completion of chemotherapy regimen. In other words, our study emphasizes functional vitamin B12 deficiency related anemia among cancer patients after the completion of chemotherapy regimen. In a brief, functional vitamin B12 deficiency is the main cause of macrocytic anemia among cancer patients.
In the present study, current dietary intake of patients which were assessed by 24HR, showed a significant reduction in their intake. Dietary intake in terms of macronutrients and micronutrients changed significantly after the completion of chemotherapy regimen. It’s expected that changes in dietary intake of patients, a reduction in macronutrient and micronutrient intake, predict a high probability of nutrient inadequacy in patients and can predict depletion in supplies of serum and tissues during their treatment period and after the completion of chemotherapy regimen. Herein our findings previously mentioned assert albumin, vitamin B12, vitamin B6 and folate deficiency after the completion of chemotherapy regimen.
As mentioned in the previous investigations, diminished nutrient intake may be attributed to anti-cancer therapy, cancer itself or other factors related to host and tumor site interaction [61]. Chemotherapy treatment may have an influence on the energy requirements of the patients and put them in a catabolic state, on the one hand, and impair their dietary intake as a result of chemotherapy‐related side effects such as nausea, vomiting, loss of appetite and taste changes, on the other hand [62, 63, 64]. Chemotherapy-induced nausea and vomiting (CINV) are considered symptoms that influence nutrient intake and that can result in malnutrition [29, 65, 66]. A retrospective study of 13 patients diagnosed with bone and soft tissue sarcomas and received consecutive-day chemotherapy reported that CINV was associated with decreased dietary energy intake during chemotherapy [67].
The current study asserts a significant change in each of the macronutrient (protein, fat and carbohydrate) and total energy intake after the completion of chemotherapy regimen. In a similar trend, a statistically significant difference demonstrated for most of micronutrient intake (calcium, iron, phosphorus, zinc, thiamin, riboflavin, vitamin B6, vitamin B12, folate and niacin), but no significant difference found for vitamin A and vitamin C. In this study, protein intake as a component of total energy intake significantly declined after the completion of chemotherapy regimen. Lower protein and energy intake is well proven to be in relation to lower micronutrient intake [68]. Gudny Geirsdottir and his colleagues found a significant negative nitrogen balance in lung, breast and colon cancer patients under chemotherapy despite their normal energy and protein intake [69]. Thus, our findings of dietary changes, macro- and micronutrient reduction, after the completion of chemotherapy regimen accompanied by a significant reduction in serum vitamin B12, MMA, Hcy, HoloTC, vitamin B6, folate and albumin and C score by SGA “malnutrition” assert that these cancer patients have a deteriorated nutritional status.
A reduction in micronutrient (B2, B3, B6, B12 and folate) intake can be attributed to the decreased total energy intake, as the resources of B vitamins are mainly whole grains, which were reduced in patient’s dietary intake due to several gastrointestinal symptoms including intake-limiting CINV, appetite loss, taste changes and other oral intake difficulties [70]. Moreover, lower intake of dark green vegetables, nuts and dairy products which are rarely part of a hospital-based diet, could also result in the poor quality of diet. Another important point that emerged during the study was doctor’s recommendations regarding restricting intake of fresh vegetables. Patients were told the reason is because of their vulnerability to the infection due to a general weakened immune system during induction therapy. Physicians had microbial safety concerns in case these vegetables had not been properly washed. More important than that, advices that given to cancer patients either by doctors, internet or TV to limit intake of animal products, mainly red meat, poultry and dairy products which are the natural source of vitamin B12.
Consistent to our findings, a review by Strohle et al. of cancer patients has found a deteriorated dietary intake in terms of macro- and micronutrients due to the side effects of treatment‐induced nutrition impact symptoms such as anorexia, nausea and vomiting [71]. A study on dietary intake of newly diagnosed acute lymphoblastic and myelogenous leukemia patients reported a further reduction in macro‐ and micronutrient intake (vitamin B1, B3, B6 and iron), after the first induction of chemotherapy, which can, to some extent, be attributed to the drug side effects [72].
Additionally, a prospective study conducted by Custodia and his colleagues among 55 women diagnosed with breast cancer to evaluate the treatment impact on the diet and nutritional status of women with breast cancer using 24HR and anthropometric measurements showed that chemotherapy interferes in patients diet generating a negative impact on diet quality, with a significant reduction in the intake of macro and micronutrients, with a high prevalence of inadequacy, of up to 100% for calcium, iron, phosphorus, magnesium, niacin, riboflavin, thiamin, vitamin B6, vitamin C and zinc [73]. In this latter study, they concluded that if the decreased dietary intake resulting in malnutrition is not compensated by early intervention, further failure in QoL and treatment outcome can be expected. The same conclusion was also derived elsewhere [74].