Abstract
Aim: Determination of the optimal nutritional parameter to provide useful information for the individual patient and assessing the impact of nutritional status have on the prognosis of head and neck cancer. Patients and Methods: Firstly a retrospective study analysed the outcome of 110 patients in relation to initial weight loss and weight loss at the end of radiotherapy. A second study investigated the changing bioimpedance (BIA) data of 27 survivors and 39 patients who died between their first and last measurement during nutritional therapy (at least four weeks). Results: A critical initial weight loss is 10 kg or more at the point of diagnosis. At the end of radiotherapy the body mass reduction should be less than 15 kg. Raw data of BIA reflect the changing nutritional status at the end of life. We observed a stabilized phase angle in survivors (4.7° to 5.2°) whereas patients who died exhibited a significant lower phase angle (4.6° to 3.7°, p<0.05). Conclusion: The prognosis of head and neck cancer patients is highly related to their nutritional status. Specific nutritional anamnesis (initial weight loss, total weight loss, body mass index) and additional biophysical measurements such as BIA are recommended to monitor the individual status during the follow-up.
Head and neck cancer is newly diagnosed for 14000 patients in Germany per year. The treatment includes surgery, radiotherapy, and treatment with chemotherapeutics or antibodies. A common side-effect of therapy is the development of dysphagia and other disturbances of daily nutrition intake (1).
Currently there are no good markers of the prognosis of cancer disease. Tumour markers have been investigated and have a high specificity, but low sensitivity (2). Hence, other clinical and non-clinical signs, which allow to specify the prognosis of an individual are sought. Therefore, we performed two analyses in a group of patients with head and neck cancer patients in order to describe the relation between nutrition and prognosis of individual patients.
Some years ago we tried to describe a critical point of no return in regard to the loss of body mass (3). These earlier data will be presented as the first part of this article as study 1. The second part will report new biophysical measurements of impedance in cancer patients during their disease course.
Patients and Methods
Study 1. 110 patients were included to a retrospective analysis of total survival and disease free survival in relation to the initial loss of body weight (time of diagnosis) as well as the loss of body weight until the end of radiotherapy. All patients were treated at the departments of ORL (Chair: PD Dr. Klaus Küttner) and radiotherapy (Chair: PD Dr. Dietmar Fröhlich) of the Municipal Hospital Suhl. All patients suffered from squamous cell carcinoma of the head and neck region and had shown an advanced stage of the disease. The standard therapy regimen included laser surgery plus neck dissection plus simultaneous radio-chemotherapy with a total dose of 60-70 Gy and carboplatin as radio-sensitizer. If the tumour was not resectable, the patients received simultaneous radio-chemotherapy only.
Table I summarizes the biometric data of the included patients, the performed therapies, and the tumour localizations.
The regional tumour data base of the state of Thuringia was used to obtain official information about the survival of each patient included. Anamnesis data were recorded from the individual data files at the both Departments, resulting in individual data sets for each patient, including three parameters: survival time, initial weight loss, weight loss by the end of treatment. All data were used for Kaplan-Meier calculations performed by MW, statistican of the Thuringian Tumour Registry at Suhl. The following procedure was used to find out the critical level of weight loss: The study population was divided into two groups with weight loss less and more of the possible critical point and the median survival time and 5-year-survival were compared. We defined the critical level of weight loss as the weight loss with disadvantages in survival time and survival percentage.
Study 2. A total of 66 patients were included for the measurement of bioimpedance (BIA) during their consultations of the Outpatient clinic of the Department of Otolaryngology at the Nordhausen Municipal Hospital. These patients were treated by the Departments of Otolaryngology, Head Neck Surgery (JB) and Radiotherapy (WO) at Nordhausen between 2008 and 2010. The patients suffered from SCC of the head and neck at an advanced stage of the disease. The basic therapy strategy was similar to the regimen described above.
BIA was performed every four weeks during the regular follow up visits after finishing baseline treatment. Measurements were carried out by qualified staff. BIA produced resistance, and reactance as raw data and both were used to calculate the phase angle as the specific parameter. All patients were participators of nutritional support therapies because of malnutrition and/or dysphagia. Between 2009 and 2011, we performed BIA in 66 male patients with head and neck cancer, 27 (41%) were still under follow-up observation, and 39 (59%) of the patients had already died. We analyzed the first and the last measurement of bioimpedance of each patient (interval at least 4 weeks). All BIAs were performed with Biacorpus RX4000 (MediCal GmbH, Karlsruhe, Germany). Table II summarizes biometric data of the included patients per group.
The relation between BIA data and prognosis of cancer disease was analyzed by comparing the phase angle of the first and last measurement in the group of surviving patients, as well as in the group of patients who had already died, using Mantel-Haenssel χ2-test for dependent study populations.
Results
Table III shows the overall survival rates and survival times according to the different critical points of initial weight loss. Reflecting the p-values, an initial weight loss of 5 kg or more is critical for the individual prognosis of the patient.
Table IV shows the overall survival rates and survival times according to the different critical points of total weight loss at the end of radiotherapy. Reflecting the p-values, a total weight loss of 12.5 kg or more is critical for the outcome of the individual patient.
As shown in Figure 1, only a quarter of all head and neck cancer patients were well nourished.
Figure 2 shows the different development of the BIA phase angle in survivors and patients who died during nutritional therapy. The survivors benefited from nutritional support and the nutritional status improved or stabilized at the second measurement. In dying patients a statistically significant decreasing phase angle was found despite nutritional therapy (p<0.05).
Table V summarizes the development of body mass index (BMI) between the time points of BIA measurement.
Discussion
Poor nutritional status is related to poor prognosis of cancer disease (4). This well known phenomenon was seen in both of our studies. The consequence is that structured support is required for patients with nutritional problems. Which diagnostic measurements are able to give us the most relevant information? The WHO and others have defined cachexia as a BMI <18.5 kg/m2. This definition was a consensus of the members of international organizations, but it does not reflect the special situation of patients with chronic diseases such as cancer (5). Malnutrition of a patient should be defined as an unwanted weight loss of >5% (or >10%) in three (or six) months, or a reduction of BMI to less than 21 kg/m2, or specific laboratory changes (C-reactive protein, albumin, protein, trace elements, vitamins) on the basis of dysphagia or other disturbances of natural nutrition (6). Reflecting this definition, it is possible that patients with higher body weight may become malnourished. These are our high-risk patients in daily work.
Specific nutritional anamnesis seems to be the first essential step in nutritional therapy. An initial weight loss of 10 kg or more is related to higher mortality, as well as a total weight loss of 15 kg or more at the end of baseline therapy. Both values are calculated as critical points and such losses should be avoided.
In order to standardize the nutritional anamnesis, we have introduced the usage of screening tools at our Department. We use the Nutritional Risk Score 2002 (NRS 2002) (7) as such a tool for each of our tumour patients.
The anamnesis should be completed by measuring body mass and length and a second objective measurement value. Possible methods are the measured dynamic hand craft (manual force measurement), the defined skin fold measurement or the bioimpedance analysis. In our experience, dynamic hand craft is a very sensitive method with high inter-individual differences. The measurement of skin folds is easy but needs time. It is possible to obtain sufficient data about body cell mass by skin fold measurements (8). Similar data are produced by BIA (9).
BIA has to be performed in a standardized manner (electrodes at each extremity, 5 cm distance between the electrodes). The patient should be in a still position for 5-10 minutes. The measured data include reactance, resistance and phase angle of the patient. All parameters reflect the personal distribution between water, and cellular parts of the body. A phase angle <5° characterizes a patient who develops malnutrition. A phase angle <4° is characteristic of malnourished high-risk patients. The raw data allow the calculation of an individual Piccoli vectograph (10). This vectograph is very helpful to visualize the personal nutritional situation and to discuss the consequences with the patient and his relatives.
Our presented data have shown the high sensitivity of BIA changes related to progressive tumour disease. Similar reports were made by Ott et al. who measured raw BIA data in patients with HIV syndrome and described a high predictability of the method regarding the survival of included patients (11). The BIA method should be used in daily practice as a simple measurement procedure providing additional information of the patient's general status.
Figure 3 shows the performance of BIA by our staff during the weekly visit of ambulant patients. Laboratory data are useful but not obligatory. The C-reactive protein has shown to be the most sensitive parameter regarding sarcopenia (12). Decreased protein or albumins are characteristic as well as disturbed homeostasis of the trace elements selenium or zinc (13).
Footnotes
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The article is dedicated to Professor Manfred Anke, the pioneer of nutritional research in Thuringia.
- Received February 13, 2012.
- Revision received April 27, 2012.
- Accepted April 27, 2012.
- Copyright© 2012 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved