Olfactory Disorders in Oncology – an Overview

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Peer-reviewed | Manuscript received: May 26, 2014 | Revision accepted: October 06, 2014 Olfactory disorders in oncology – an overview

Sabine Chmelar, Mödling/AT, Andreas Temmel, Perchtoldsdorf/AT, Peter Kier, Wien/AT, Herman Toplak, Graz/AT, Elisabeth Pail, Bad Gleichenberg/AT

influence the sense of smell [4, 5]. Summary Whereby in hunger the olfactory function improves and the stimulus Currently olfactory disorders in cancer patients are often seen as a minor matter, threshold for odors declines [6]. but they actually deserve more attention. Literature shows that tumor diseases and their treatment can affect the olfactory perception of the patients. Olfactory disorders impair quality of life, lead to loss of appetite, decreased nutrient intake Definition of olfactory disorders and therefore are subsequently risk factors in the complex development of mal- • Table 1 provides an overview on the nutrition. different manifestations of olfactory More scientific work is needed for a better understanding of olfactory disorders disorders (dysosmia). and their impact on oncological patients, to explore new therapeutic approaches and scientifically reinforce nutritional therapeutic recommendations. As a result Scientific studies focusing on olfactory of improving the dietary condition, the therapeutic effectiveness as well as the disorders in patients with an oncolo- quality of the patients’ lives can be improved. gical primary disease cover very hete- Changes in the perception of odors by patients in oncological care are not only rogeneous patients groups in terms of burdensome for those affected, but also pose a challenge for the dietician. This ar- tumor type, stage, therapy, etc. There- ticle aims to provide an overview on the latest information concerning this topic. fore results are very hard to compare Keywords: olfactory disorders, oncology, malnutrition, quality of life, diet therapy to each other and data, such as the incidence of olfactory disorders, vary considerably [9, 10]. The olfactory sense Nutritional relevance Besides its function in food intake, olfaction is closely linked to our emo- Prevention of malnutrition, accompa- tions. On the one hand the classifi- nying an improvement of the subjec- cation in good and bad odors is ge- tive state of quality of life and an in- netically determined, e.g. to recognize crease in effectiveness of the therapy, spoiled food, on the other hand it is is a major therapeutic goal in nutri- strongly shaped by cultural influen- tion therapy of oncological patients ces on us. In addition, perception of [11–13]. Changes in odor perception the body odor of other people fulfills are – among other symptoms such as an important social function, such as alopecia (loss of hair), dysgeusia (alte- the newborn‘s capability of finding rations of the sense of taste), fatigue, Zitierweise: the mother‘s mammilla [1–3]. etc. – a strong limiting factor in every- Chmelar S, Temmel A, Kier P, day life of cancer patients [14] and Toplak H, Pail E (2015) Olfacto- The human ability of smell percep- one of many symptoms that affect ry disorders in oncology – an tion is dependent on various factors. food intake significantly [15]. A - re overview. Ernahrungs Umschau Advancing age and consumption duced sensitivity or changes in odor 62(1): 2–7 of tobacco both decrease olfactions. and flavor perception are associated Physiological factors, such as hor- with decreased nutrient intake and the This article is available online: monal status or regulatory mecha- development of food aversions [9]. DOI: 10.4455/eu.2015.002 nisms in hunger and satiety, can

2 Ernaehrungs Umschau international | 1/2015 Quantitative odor distortion hyperosmia exaggerated sense of smell normosmia normal sense of smell hyposmia decreased ability to detect odors anosmia total inability to detect odors functional significant limitation with low residual perception partial significant reduced sensitivity to one or more specific fragrances Qualitative odor distortion parosmia altered perception of smell in the presence of an odor phantosmia perception of smell without an odor present pseudosmia imaginative reinterpretation of an odor under the influence of strong emotions olfactory intolerance exaggerated subjective sensitivity to fragrances in normal sensitivity agnosia inability to classify or contrast odors, although able to detect odors

Table 1: Definition of olfactory disorders [7, 8]

Currently, odor or taste problems are might interfere with the regeneration In addition, Schiffmann supports the not routinely questioned or clarified. of the olfactory neurons from the theory that the presence of the tumor This might be due to the lack of in- basal cells [18], although the reasons leads to metabolic changes that affect struments to investigate in a brief for this are yet not fully understood. the sensory perception, or complica- and concise way whether dysosmia is Suitable explanations would be a re- tions such as stomatitis (inflammation present or not. Furthermore, the dif- duced number of receptor cells through of mucous lining of any of the struc- ferent forms of olfactory dysfunction destruction or a negative effect on cell tures in the mouth), dry mouth and in- in cancer patients complicate detec- renewal, changes in cell structure or fection might also play a role [19]. Ad- tion. In addition, the current dietary changes in receptor surface or inter- ditionally a pre-existing malnutrition of recommendations (such as choose cold ruption of neural coding [9, 19]. the patient concerned could be the cause food, avoid strong odors, etc.) are of Substances for tumor therapy, in stu- of odor and flavor changes [20]. rather trivial nature and scientifically dies repeatedly associated with smell unsubstantiated [15]. Attempts at the- and taste disorders, are doxorubicin, Methodological problems in rapy with zinc also have not shown methotrexate, cisplatin, carmustine the identification of olfactory any positive results [16]. and vincristine [19, 20]. disorders A Japanese study by Suga et al. with Smell and taste changes have a funda- 136 patients showed that a wide va- Patients’ interviews confirm that smell mental impact on the lives and the diet riety of chemotherapeutics have a ne- and taste disorders are perceived quite of the persons affected. It is not solely gative effect on olfactory performance. differently in terms of severity, effects, about the nutrient intake and food 31 % of patients who received doceta- etc. and that patients show both: either selection, but also about the social xel and fluorouracil, 22 % of patients a decreased or an increased sensitivity component of the food environment, with a paclitaxel therapy and 23 % tre- to odors. One reason for the different subsequently affecting the quality of ated with the HER-2-antibody trastu- results is the methodology of the detec- life. Early detection of smell and taste zumab reported an olfactory dysfunction of olfactory dysfunction. Patients disorders would be necessary for the tion [21]. may not be able to distinguish between timely prevention of malnutrition. A recent work by Steinbach et al. exa- taste and smell when explaining their mined the impact of carboplatin-con- subjective impressions, or by a change Explanatory theories taining chemotherapy drugs on the of olfaction they understand that smells for olfactory disorders senses of smell, taste and hearing. Du- smell different than before, but not that ring therapy the sense of smell decrea- the odor threshold changes [23, 25]. in cancer ses significantly and – as confirmed in Based on animal studies, the average other studies [22, 23] – is recovered lifetime of olfactory neurons is estimat- after about three months [24]. ed at 30 or 90 days [8, 17]. The cytotoxic effects of chemotherapy ▸

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Patients Reference Methods Results n Characteristics Ovesen et al. 1991 [29] 51 cancer of the lung, ovary determination of olfactory detection thresholds no significant differences in smell thresholds were found between patients with cancer and control patients or breast by the method of Amoore and Ollmann (n = 29) before chemotherapy and after the third cycle of chemotherapy Epstein et al. 2002 [30] 50 high-dose chemotherapy 90–100 days post transplantation 8 % smell decreased and allogeneic stem cell QOL-questionnaire (QLQ-C30) 26 % smell sensitivity increased transplantation 24 % change in smell Change in smell correlated with change in taste (p < 0.01)

Yakirevitch et al. 2005 [31] 21 chemotherapy including Sniffin‘ Sticks odor identification test kit before beginning che- A decrease in olfaction was noted in one patient (4.7 %) cisplatin motherapy, after each course and 3 weeks after the last course Yakirevitch et al. 2006 [32] 42 oncological patients in Sniffin‘ Sticks odor identification test kit 60 % (n = 25) decreased olfaction – the majority of them (n = 20) were not aware of the problem hospital treatment An earlier chemotherapy or radiotherapy had no significant influence on the olfactory score

Hutton et al. 2007 [33] 66 patients with advanced three-day dietary record 86 % (n = 57) reported some type of chemosensory abnormality, of those: cancer (locally recurrent or targeted interviews - 34 patients (52 %) had both smell and taste complaints metastatic) questionnaire about self-perceived smell and taste function - 20 patients (30 %) described only taste complaints Functional Assessment of Anorexia/Cachexia Therapy (FAA- - 3 patients (5 %) described only smell complaints CT) patients with severe chemosensory problems showed substantially lower energy intakes (by 900 –1100 kcal/d) than patients without chemosensory problems → significant major weight loss in the last 6 months. Smell and taste complaints are followed by a lower quality of life, lack of appetite, nausea and early satiety

Bernhardson et al. 2008 [26] 518 cancer patients receiving questionnaire 75 % (n = 387) reported some form of chemosensory change, of those: chemotherapy - 213 patients (41 %) had both smell and taste changes (≥ 6 weeks) - 134 patients (26 %) reported taste changes alone - 40 patients (8 %) reported smell changes alone Taste and smell changes are more prevalent in women than men (79 % vs. 59 %; p < 0.01) and showed no association with self-reported weight changes

Brisbois et al. 2011 [34] 192 advanced cancer patients questionnaire about self-perceived smell 26 % (n = 49) no change (locally recurrent, locally and taste function 42 % (n = 81) stronger sensation overall advanced or metastatic) 18 % (n = 35) weaker sensation overall three-day dietary record 14 % (n = 27) mixed sensation Edmonton Symptom Assessment Scale (ESAS) compared with patients reporting no chemosensory alterations, patients with smell and taste changes are Functional Assessment of Anorexia/Cachexia having: Therapy (FAACT) - lower energy intake (p < 0.01) - higher weight loss (p < 0.01) Patient Generated Subjective - lower QOL scores (p = 0.02) Global Assessment (PGSGA)

Tab. 2: Overview of study results on olfactory disorders in cancer patients

Current study results a dose of chemotherapy, which can be Frequent subjective complaints – based explained by the diffusion of the drug on the chemosensory perception – are a According Brisbois et al., smell and taste from the capillaries in the nasal mucous bad taste in the mouth, changes in taste changes are observed in 50–90 % of ad- into the olfactory receptors [18]. and altered sensitivity to odors. The alte- vanced stage cancer patients. The cha- Patients with smell or taste disorders red sense of olfaction – which, as already racteristics can be of both quantitative are more likely to report oral problems, shown above, is usually associated with (e.g. altered sensitivity) as well as of such as dry mouth, aphthous ulcer or a change in taste – can be expressed by qualitative nature (e.g. phantom smells) mucositis, loss of appetite, nausea and an unpleasant perception of especially [15]. Additionally, patients often de- depressive mood than patients without food odors, but also by other odors, such scribe odors during or immediately after smell and taste changes [26]. as perfume, smell of hospitals, etc. [27].

4 Ernaehrungs Umschau international | 1/2015 Patients Reference Methods Results n Characteristics Ovesen et al. 1991 [29] 51 cancer of the lung, ovary determination of olfactory detection thresholds no significant differences in smell thresholds were found between patients with cancer and control patients or breast by the method of Amoore and Ollmann (n = 29) before chemotherapy and after the third cycle of chemotherapy Epstein et al. 2002 [30] 50 high-dose chemotherapy 90–100 days post transplantation 8 % smell decreased and allogeneic stem cell QOL-questionnaire (QLQ-C30) 26 % smell sensitivity increased transplantation 24 % change in smell Change in smell correlated with change in taste (p < 0.01)

Furthermore, there are individual case olfactory function had improved in an special focus on the particular group reports, such as that of a 63-year-old extent, even without this clip sufficient of breast cancer patients. In 2007, a woman with acute lymphoblastic oral food intake was possible [26]. total of 69 breast cancer patients and leukemia and chemotherapy-associ- • Table 2 provides an overview of the 18 patients with other gynecological ated parosmia, which resulted in life- current study results. malignancies were recruited in diffe- threatening weight loss. The problem rent hospital centers in order to exa- was eventually solved temporarily mine the effects of chemotherapy on Study results with a nose clip that prevented her from olfactory performance. A smell test in breast cancer patients smelling anything at all. After nine with Sniffin’ Sticks was performed months without chemotherapy, the Steinbach et al. in Germany have a on the patients before, during, directly ▸

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after and three months after the end mean (± SD) of chemotherapy. Both, the total value and all three subtests (thresholds, week 0 8.1 (± 2.1) identification and discrimination week 9 6.1 (± 1.7) test), showed a significant reduction week 18 4.9 (± 1.3) in olfactory performance during che- week 30 7.1 (± 1.8) motherapy, wherein the threshold test was the most and the identification test the least affected [22]. Three months after chemotherapy, the olfactory performance has recovered, confirming the results from a qualitative study, also showing a recovery time of about 3.5 months after the end of chemotherapy [23]. • Figure 1 presents the thresholds of all patients over time.

In another study, Steinbach et al. re-analyzed the data of 69 breast Figure 1: Box-Whisker-Plot with odor threshold scores for all patients measured cancer patients more precisely. From before (0 weeks), during (9 weeks), directly after (18 weeks) and 3 this could be seen that before chemo- months after (30 weeks) chemotherapy. therapy the total value of the Sniffin’ There is a significant decrease in the odor threshold score during and directly after chemotherapy (p < 0.001) [22] Sticks test decreased significantly with SD = standard deviation bigger tumor size and with increasing lymph node involvement, whereas with the latter’s the patients’ age may have played a role as a potential con- dations in the future. 2 Medizinische Universität Wien founder. The presence of metastases, The identification and observation of Brunnergasse 1 9/4/4, 2380 Perchtoldsdorf/AT the resection status, or the histological these symptoms may improve the E-Mail: [email protected] 3 SMZ-Ost/Donauspital type of breast cancer had no effect on holistic approach of the medical treat- Langobardenstraße 122, 1220 Wien/AT the sense of odor or taste of the pa- ment of oncologic patients, particu- E-Mail: [email protected] tients [10]. larly in respect of olfactory disorders 4 Medizinische Universität Graz This study found no correlation bet- being one factor in the development of Auenbruggerplatz 15, 8036 Graz/AT ween the smell and taste performance malnutrition. E-Mail: [email protected] 5 FH Joanneum Bad Gleichenberg and the hormone receptor status of Kaiser-Franz-Josef-Str. 24, estrogen and progesterone and the ex- 8344 Bad Gleichenberg/AT pression of HER-2. This is in contrast E-Mail: [email protected] to a study conducted in 1985, in which Conflict of Interest The authors declare no conflict of interest estrogen-positive breast cancer patients according to the guidelines of the International had a significantly reduced olfactory Committee of Medical Journal Editors. performance compared to the matched controls, and these results did not cor- relate with estrogen-negative subjects [35]. However, this result could be explained by the higher average age in the Sabine Chmelar, MSc1 2 estrogen-positive group [10]. Univ. Prof. Dr. Andreas Temmel Dr. Peter Kier3 Univ. Prof. Dr. Hermann Toplak4 Conclusion Elisabeth Pail, MSc, MBA5

Current study results on olfactory di- 1Universitätslehrgang „Applied Nutrition sorders in oncologic patients are very Medicine“ Medizinische Universität Graz heterogeneous and raise a lot of ques- FH Joanneum Bad Gleichenberg tions. Therefore, further studies are Prießnitzgasse 19/1, 2340 Mödling/AT necessary to make proper recommen- E-Mail: [email protected]

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