Food experience in cancer patients undergoing antineoplastic therapies - Affective responses to food and inputs for new tailor-made food solutions

Although the advances in cancer management, particularly with the advent of immunotherapy, chemotherapy remains the most widely used treatment approach. However, its limited selectivity leads to cytotoxic effects also on rapidly renewing cells, including taste and olfactory receptors. Chemosensory alterations represent therefore a frequent side effect, affecting up to 93% of patients undergoing chemotherapy. Despite this high rate these alterations are considered “orphan symptoms”, as they are generally unaddressed in clinical practice. Yet chemosensory alterations, may impact the patient's daily eating experience by altering the palatability of foods, leading to aversion for certain dishes and changes in food preferences and behaviors. Furthermore, the loss of the ability to enjoy favorite foods can exacerbate emotional responses and trigger concern and anxiety in patients, making participation in social gatherings more challenging, worsening the quality of life. The unexpected occurrence of chemosensory alterations can lead to significantly different, and sometimes opposing, outcomes: on the one hand, loss of appetite, reduced food intake, failure to meet nutritional needs, and consequent weight loss; on the other, satisfaction of specific food cravings, increased caloric intake, and consequent weight gain. Both scenarios place patients at high risk of malnutrition. Nutritional support is not used as routinely as an adjunct to antineoplastic therapies as chemosensory alterations are often considered as unavoidable side effects of treatment. In addition, the accessibility to a variety and attractive food products is limited for oncological patients. Although a variety of oral nutritional supplements are currently available on the market, there is a notable lack of food products specifically designed for cancer patients experiencing chemosensory alterations. Furthermore, the dietary advice currently offered in oncology is often generic and non-personalized, failing to adequately address the individual sensory and nutritional challenges patients face during treatment. Given the complexity and multidimensional nature of chemosensory alterations in cancer patients and considering their significant impact on both nutritional status and emotional well-being, a deeper understanding of this phenomenon is essential. Such understanding is necessary to develop personalized nutritional interventions that effectively meet patients' specific needs, improve their quality of life, and help restore the pleasure of eating. The overall goal of this thesis is therefore to explore the phenomenon of chemosensory alterations as a side effect of anticancer treatment and to understand the impact of these disturbances on the daily eating experience and quality of life, focusing on food preferences, emotional responses to foods, eating habits, and nutritional status. This impact also varies according to individual differences (e.g., food neophobia, disgust sensitivity, PROP responsiveness). This will allow us to develop personalized recommendations and input for new products and recipes tailored to the needs of cancer patients, improving their eating experience, nutritional status, and quality of life. The data of the thesis were collected as part of the larger ongoing ALTERTASTE project on a total of 71 patients with a mean age of 50.5 ± 12.6 years, treated with platinum-based or taxane-based chemotherapy for breast, bladder, prostate or testicle cancer. Patients were followed longitudinally across multiple session: before the treatment (T0), 58 patients after the 1st cycle (T1), 66 patients after the 2nd cycle (T2), 57 patients after the 4th cycle (T4), 42 patients at (T6), 33 patients at (T8), 56 patients at (TF). Chemosensory perception was measured using suprathreshold aqueous solutions at lower/higher concentration presented for basic tastes (sweet, salty, sour, bitter) and a pungent sensation. Self-reported chemosensory alterations are collected using an adapted version of the Italian Chemotherapy Induced Taste Alteration Scale. Self-reported taste/smell ability and chemestetic perception during treatment were collected using an adapted version of a questionnaire set up to measure chemosensory changes due to COVID-19, together with a questionnaire developed for the study assessing changes in hedonic responses to basic tastes and changes in eating habits (use/liking of condiments) during treatment. Food Preference and Emotion Questionnaire (FP&EQ) was a new tool developed specifically for the study, in order to track any changes in preferences and emotions elicited by foods differing in key sensory properties during the whole treatment period. Food involvement of patients was assessed using the subscale “Preparation and eating” of the Food Involvement Scale. Body composition (weight, fat mass, lean mass) was determined through a bioelectrical impedance analysis device (TANITA, model BC-613). To understand the impact on quality of life the European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC-QLQ 30) was used. PROP responsiveness, food neophobia and sensitivity to disgust were measured to investigate their role in the development of chemosensory alteration during therapy and in food preferences and emotional responses. Finally, qualitative semi-structured interviews allowed for further insight into chemosensory alterations and their impact on the eating experience. The study shows that chemotherapy induced a variety of chemosensory alterations, detected through both sensory tests and self-reported questionnaire. Although the ability to correctly identify basic tastes and pungent in aqueous solutions remained generally preserved, a significant reduction in the perception of intensity was observed, especially for sweet and salty, even in the early stages of treatment, at both the lower and higher concentrations. From a self-report perspective, the alterations emerged very early. Already after the first cycle, 39.7% of patients reported general alterations/parageusia/increased perception and 44.8% reported phantogeusia. The decline in basic taste perception was particularly reported after the second cycle, affecting half of the sample. These alterations tended to increase during treatment, with subsequent recovery three months after the end of chemotherapy. PROP responsiveness remained stable throughout treatment and reflected individual differences in taste and trigeminal sensitivity. Patients High PROP responders reported more severe taste alterations, particularly phantogeusia, at certain stages of therapy, although there was no consistent association over time, suggesting that increased taste sensitivity may enhance the perception of sensory changes. Regarding food experience, patients showed highly heterogeneous responses to chemosensory alterations. Although no immediate changes in food preferences emerged after the first cycle of therapy, emotions associated with habitually liked foods began to worsen early on, especially in the Sweet vs. Bitter dimension of FP&EQ, both basic tastes influenced by changes in liking. As treatment progressed, changes in food preferences were observed, especially in patients with general taste alterations/parageusia/increase in taste perception. The preference changes regarded particularly Texture and Flavor dimensions. Some patients preferred more flavorful foods or additional seasonings to compensate for a reduced or altered taste perception, while others showed the opposite tendency, turning to milder foods to avoid unpleasant or distorted sensations. This variability reflects the adoption of personal and non-unique coping strategies aimed at rediscovering the food pleasure and preventing weight loss. At the same time, patients with chemosensory alterations reported worse quality of life across several domains, including physical condition, fatigue, social and emotional functioning, and experienced more pronounced treatment-related symptoms, such as nausea, vomiting, and loss of appetite. These findings indicate that taste perception disorders have consequences that extend well beyond the experience of eating, affecting general well-being, while not affecting body composition. The "ideal snack" analysis indicated that chemosensory changes did not result in distinct sensory preference profiles across the different types of changes. Overall, salty snacks were consistently preferred throughout treatment, with crunchy and tasty identified as the most desirable attributes. Conversely, pasty, liquid, or excessively soft textures were generally avoided, likely reflecting the high prevalence of oral discomfort, already reported by 47.9% of patients before treatment and increasing to 81% after the first cycle and 87.9% after the second. These findings highlight the importance of prioritizing flavor intensity and texture in dietary interventions for patients undergoing chemotherapy, supporting the development of personalized sensory and nutritional strategies. Based on data collected through questionnaires and interviews, it was possible to identify different profiles of chemosensory alterations. However, these profiles did not translate into homogeneous patterns, as the response to these alterations was often highly individual, with patients adopting personal strategies, sometimes compensatory or, conversely, avoidance, to maintain the pleasure of food during treatment. From the analysis of these alterations and their impact on the eating experience, personalized sensory and nutritional recommendations were developed, based on taste-odor integration, with the aim of improving palatability without impacting health through increased salt or sugar intake. The recommendations were translated into practical advice and recipes adapted to individual profiles, providing a basis for the development of tailor-made dietary solutions aimed at preserving the pleasure of food and supporting nutritional status during therapy.