Assessment of Quality of Life in Patients Treated with Chemo and Radiotherapy for Gastric Cancer

FACULTY OF MEDICINE – UNIVERSITY OF PORTO Department of Biostatistics and Medical Informatics Introdução à Medicina 2005/2006

Assessment of Quality of Life in Patients treated with Chemo and Radiotherapy for Gastric Cancer

Catarina Costa Dalila Ruivo Mafalda Couto Manuel António Campos [email protected] [email protected] [email protected] [email protected] Márcio Tavares Margarida Leite Maria Alexandra Maria Brandão Rodrigues [email protected] [email protected] [email protected] [email protected] Maria João Abreu Mariana Ferreira Nuno Soares Tiago Meirinhos [email protected] [email protected] [email protected] [email protected] Supervisors: Altamiro da Costa Pereira, MD, PhD, [email protected]; Mário Dinis Ribeiro, MD, PhD, [email protected]; Cláudia Camila Dias, MSc, [email protected]; Class: 14

Abstract Introduction: Gastric cancer is one of the most frequent types of cancer. There is a variety of effective treatment options for gastric cancer. Thus, there is a decreasing in the death rate of this type of cancer. At the same time, the Quality of Life (QoL) of the patients after treatment, when compared with QoL before treatment, acquires a large relevance. Aim: To review which instruments were used to measure the QoL in patients with gastric cancer submitted to chemo and radiotherapy and to summarize QoL measures across studies. Methods: A systematic review was conducted on Medline. The query used was: ″Gastric cancer AND (Quality of Life OR Psychology) AND (Radiotherapy OR Chemotherapy)”. After the literature search, the titles of all the articles found were read and then all the abstracts were read too. Then the inclusion and exclusion criteria were defined and applied to the articles. Results: Starting with one hundred and sixteen articles, twenty were unavailable, so, ninety six were submitted to our selection using the defined criteria. In the end, only eleven were fully analyzed. The instruments used to access QoL (in almost every cases EORT-QLQ C30, but also HADS and RSCL) are all validated. Although they have a scale, the values obtained are not showed in the articles. Only qualitative analyses are presented. The patients submitted to the treatments in study have gastric cancer in an advanced stage, many times metastic Conclusion: It is clear that QoL isn’t the main concern of these papers. More research is needed in this area, to analyse the effects of chemo and radiotherapy in these patients. The major problem is lack of qualitative values (although their existence). Beside, when used alone, chemo and radiotherapy are used as palliative treatments. Because of that fact, maybe the instruments used aren’t the most appropriate choice, since there are validated instruments specifically developed for patients under palliation. Key-words: Gastric cancer [MeSH], Quality of Life [MeSH], radiotherapy [MeSH], chemotherapy [MeSH], systematic review [MeSH].

Introduction FACULTY OF MEDICINE – UNIVERSITY OF PORTO Department of Biostatistics and Medical Informatics Introdução à Medicina 2005/2006

Stomach cancer is a malignant cell growth that begins in the cells of the stomach and invades the surrounding healthy cells [1]. Stomach adenocarcinoma is the most common type of gastric cancer (95% of the cases) [2]. The exact causes of stomach cancer are not fully understood [3]. It has a high incidence in world population and Portugal is the European country where there are more people affected. Its death rate is high but has decreased due to scientific development [4]; therefore QoL is an increasing concern. Treatment for gastric cancer often involves surgery, usually a partial or a total gastrectomy (removal of stomach tissue). Chemotherapy and radiotherapy are also a standard treatment [45]. These multiple treatments have different consequences in the QoL of the patients. QoL cannot be universally defined [5] but Schipper et al. suggested that QoL is the functional effect of illness and its consequent therapy upon a patient, as perceived by the patient [6]. Functional effects can be divided in three major categories: physiological, psychological and social [5]. Is important to clarify not only if chemo and radiotherapy are worthy options to prolong the life expectancy of the patients, but also the life changes that come with the treatment. Analyse differences of the median of survival between the group submitted to chemo and radiotherapy and the control group is effective to prove the efficacy of a specific drug. However, only patients under that kind of treatment can provide us the information necessary to realise if that drug is really efficient. That information is collected using instruments to measure QoL. So, it is extremely important make sure that the best choice is made, that the instrument is reproducible and valid. Otherwise the results obtained won’t improve the knowledge of the area in study. The purpose of this paper is to summarize (estimate in a single value) the QoL of patients with gastric cancer after treatment with chemo and radiotherapy, carrying on a meta-analysis. As a secondary aim we pretend clarify validity/validation of instruments used and summarize (estimate in a single value) the QoL of patients with gastric cancer according to instrument.

Participants and Methods 1. Systematic Review and meta-analysis FACULTY OF MEDICINE – UNIVERSITY OF PORTO Department of Biostatistics and Medical Informatics Introdução à Medicina 2005/2006

A systematic review was conducted by an overview of primary studies made in this area. Then we tried to make a mathematical synthesis of the results of the included articles, i.e., a meta-analysis. 2. Search Strategy (Limits) Literature searches were conducted in Medline until September 2005. In our first attempt the query used was - "stomach neoplasm AND quality of life AND (radiotherapy AND chemotherapy)" - and we only obtained 15 articles. With the following query - "stomach neoplasm AND quality of life AND (radiotherapy OR chemotherapy)" - we achieved 98 articles. We moved on to another query - "gastric cancer AND quality of life AND (radiotherapy OR chemotherapy)" - which resulted in 108 articles. Finally, we tried another query - "gastric cancer AND (quality of life or psychology) AND (radiotherapy OR chemotherapy") - which become the basis of our work with a total of 116 articles. This query, without any kind of language limitations, resulted in 320 articles. From these number, 158 (49%) were in Japanese; 116 (36%) in English; 8 (3%) in German; 4 (1%) in Italian; 3 (1%) in French; 3 (1%) in Russian and 1 was in Spanish; 27 (8%) were in other languages. The search was then limited to: articles referent to “Humans”, written in “English” and “with available abstracts”. Articles were included or excluded after defining the proper criteria. The articles found were read by six reviewers organized in three different groups. In case of disagreement, was asked the opinion of a third reviewer. a) Inclusion and Exclusion criteria Paper inclusion criteria Included were articles with more than one participant, in witch QoL was evaluated by the patients, who had gastric cancer and were submitted to chemo or radiotherapy. QoL must be measured with an appropriate instrument. (see Figure 1) Paper exclusion criteria Excluded were articles based on mixed diagnostic groupings (in the article these have to be approached separately) and those in which QoL was measure but only symptoms were studied. Articles that referred to patients submitted to a surgery during or before treatment were also excluded. (see Figure 1) FACULTY OF MEDICINE – UNIVERSITY OF PORTO Department of Biostatistics and Medical Informatics Introdução à Medicina 2005/2006 b) Validation Paper of Questionnaires A second search was conducted, to discover if the instruments used in the included articles were valid. To find the validation papers the questionnaire was searched through Google. (see Table 1) 3. Statistical Analysis For the recording of the data from the articles found was made a Database through “SPSS 14.0 for Windows” software. About each article found were retained the title, names of first and second author, name of the journal where it was published, volume and year of publication. The database also gives information about the inclusion and exclusion criteria for each article read, data related to the criteria and if the article was included or not. For the included articles was also recorded the type of study, the number of patients, the used instrument and if it is validated or not. (see Tables 2 and 3)

Results One hundred and sixteen articles were found. However, our results are only referred to ninety seven articles because we didn’t have access to nineteen articles. 1. Articles included The titles and abstracts of all the articles were read and evaluated by reviewers. These articles were essentially meta-analysis and clinical trials. Then, the articles were totally read and, due to the application of the inclusion and exclusion criteria, the number of included articles decreased to eleven. A scheme of the process is presented below, on Figure 1. FACULTY OF MEDICINE – UNIVERSITY OF PORTO Department of Biostatistics and Medical Informatics Introdução à Medicina 2005/2006

Search in PubMed

116 articles were 19 were not available found

97 articles were analised

38 articles were excluded because they did not evaluate QOL (2, 4, 7, 8, 9, 20, 23, 24, 33, 36, 42, 47, 48, 51, 52, 53, 54, 55, 70, 72, 74, 75, 76, 81, 89, 90, 91, 93, 94, 97, 99, 100, 102, 105, 107, 109, 112, 113)

31 articled were excluded because QOL was not evaluated by the patient ( 5, 16, 17, 21, 22, 27, 29, 30, 32, 34, 40, 41, 46, 50, 56, 64, 66, 68, 73, 78, 82, 85, 86, 87, 88, 95, 96, 98, 114, 115, 116)

6 were excluded because the patients were not treated with chemo or radiotherapy ( 19, 31, 45, 77, 80, 83)

4 articles were excluded because the patients didin´t have gastric cancer (13, 25, 28, 108)

2 articles were excluded because patients were submitted to a surgery durins treatment (59, 60)

2 articles were excluded because studies were based on mixed diagnostic groups (6, 106)

2 were excluded because the authors did not use na instrument to use the qol (10, 101)

1 articles were excluded because they had only one participant (12)

11 articles were included (3, 11, 14, 35, 37, 39, 43, 65, 79, 84, 92)

Figure 1. Description of the articles selection. 2. Questionnaires FACULTY OF MEDICINE – UNIVERSITY OF PORTO Department of Biostatistics and Medical Informatics Introdução à Medicina 2005/2006

The questionnaires used in all the included articles have a validation paper. In the following table the instrument and the validation paper are presented. Table 1. Questionnaires present in the included articles and their respective validation papers. Questionnaire Name of the validation paper First author EORTC QLQ-C30 Validation of the european organization for research and McLachlan SA treatment of cancer quality of life questionnaire (QLQ-C30) as a measure of psychosocial function in breast cancer patients Rotterdam Symptom Checklist Validation of a modified Rotterdam Symptom Checklist for use Stein KD with cancer patients in the United States HADS The Hospital Anxiety And Depression Scale Zigmond AS

3. Summary of the extracted data The results obtained with the analysis of the included articles (see Table 2) showed that a quantitative measurement of QoL wasn’t made. Thus, we used the given qualitative measurement, and divided it into three different categories related with an increasing, decreasing or no different QoL after treatment with chemo or radiotherapy in gastric cancer. That is showed on Table 3. Table 2. Global features of the included articles.

Measure of Questionnaire Validation Name of First Year of Number of Age of the central Type of used Validation Second Diagnostic paper the article Author publication participants participants tendenc study to evaluate paper questionnaire y QLQ used Quality of life in patients with advanced Locally Clinical EORTC-QLQ- gastric cancer treated Park SH 2005 43 59,0 Median advanced or Yes HADS Yes Trial C30 with second-line metastic disease chemotherapy Quality of life in patients with gastroenteropancreatic Teunissen Metastic tumor Clinical EORTC-QLQ- 2004 50 58,3 Mean Yes No No tumors treated with JJ (GEP) Trial C30 [177Lu- DOTA0,Tyr3]octreotate Multivariate prognostic factor analysis in locally advanced and metastatic esophago- Randomized gastric cancer--pooled Inoperable EORTC-QLQ- Chau I 2004 1080 62,0 Median Controlled Yes No No analysis from three adenocarcinoma C30 Trial multicenter, randomized, controlled trials using individual patient data A multicentre, randomised phase III trial comparing protracted venous infusion (PVI) 5- Locally Randomized Tebbutt EORTC-QLQ- fluorouracil (5-FU) 2002 254 72,0 Mean advanced or Controlled Yes No No NC C30 with PVI 5-FU plus metastic disease Trial mitomycin C in patients with inoperable oesophago-gastric cancer. Marimastat as maintenance therapy for Locally Randomized Bramhall EORTC-QLQ- patients with advanced 2002 369 68,0 Mean advanced or Controlled Yes No No SR C30 gastric cancer: a metastic disease Trial randomised trial. Prospective randomized Ross P 2002 580 58,5 Mean Inoperable Randomized EORTC-QLQ- Yes No No trial comparing adenocarcinoma Controlled C30 mitomycin, cisplatin, Trial and protracted venous- infusion fluorouracil FACULTY OF MEDICINE – UNIVERSITY OF PORTO Department of Biostatistics and Medical Informatics Introdução à Medicina 2005/2006

(PVI 5-FU) With epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer. Alternative methods of interpreting quality of Randomized Advanced EORTC-QLQ- life data in advanced Nordin K 2001 120 64,0 Mean Controlled Yes No No gastric cancer C30 gastrointestinal cancer Trial patients. Evaluation of clinical benefit of Randomized Hoffman Advanced EORTC-QLQ- chemotherapy in 1998 61 64,0 Median Controlled Yes No No K gastric cancer C30 patients with upper Trial gastrointestinal cancer. Randomized comparison between Locally Randomized chemotherapy plus best Glimelius EORTC-QLQ- 1997 61 64,0 Mean advanced or Controlled Yes No No supportive care with B C30 metastic disease Trial best supportive care in advanced gastric cancer. Epirubicin, cisplatin, and protracted venous infusion of 5- fluorouracil for Locally Clinical EORTC-QLQ- esophagogastric Bamias A 1996 235 59,0 Mean advanced or Yes No No Trial C30 adenocarcinoma: metastic disease response, toxicity, quality of life, and survival. A phase II study in advanced gastro- esophageal cancer using Locally Rotterdam Findlay Clinical epirubicin and cisplatin 1994 139 60,0 Mean advanced or Symptom Yes No No M Trial in combination with metastic disease Checklist continuous infusion 5- fluorouracil (ECF).

Table 3. Features of the included articles related with QoL measurement. Base Final Name of First Year of First value value Percentage Second Parameter Results the article Author publication Parameter of of of patients QoL QoL Quality of life in patients Patients not QoL increases with with advanced gastric cancer Patients submitted to Park SH 2005 submitted to 56,9 69,4 37,0 second-line treated with second-line second-line chemotherapy chemotherapy chemotherapy chemotherapy Quality of life in patients Patients not Patients treated with QoL increases in patients with gastroenteropancreatic Teunissen 2004 submitted to [177Lu- 69,0 78,2 No values treated with [177-Lu- tumors treated with [177Lu- JJ chemotherapy DOTA0,Tyr3]octreotate DOTA0,Tyr3]octreotate DOTA0,Tyr3]octreotate Multivariate prognostic factor analysis in locally advanced and metastatic Patients submitted to Patients not esophago-gastric cancer-- fluoreouracil-based No No Chau I 2004 submitted to No values No differences in QoL pooled analysis from three combination values values chemotherapy multicenter, randomized, chemotherapy controlled trials using individual patient data A multicentre, randomised Patients phase III trial comparing submitted to protracted venous infusion protracted (PVI) 5-fluorouracil (5-FU) Tebbutt Patients submitted to PVI No No 2002 venous infusion No values No differences in QoL with PVI 5-FU plus NC 5-FU plus mitomycin C values values (PVI) 5- mitomycin C in patients with fluorouracil (5- inoperable oesophago- FU) gastric cancer. Marimastat as maintenance therapy for patients with Bramhall Patients submitted to No No 2002 Placebo No values No differences in QoL advanced gastric cancer: a SR chemotherapy values values randomised trial. Prospective randomized trial Patients comparing mitomycin, submitted to cisplatin, and protracted mitomycin, Patients submitted to QoL increases if we use venous-infusion fluorouracil cisplatin, and No No Ross P 2002 epirubicin, cisplatin, and No values epirubicin, cisplatin, and (PVI 5-FU) With epirubicin, protracted values values PVI 5-FU PVI 5-FU cisplatin, and PVI 5-FU in venous-infusion advanced esophagogastric fluorouracil cancer. (PVI 5-FU) Alternative methods of Patients interpreting quality of life submitted to Patients submitted to QoL increases in No No data in advanced Nordin K 2001 chemotherapy chemotherapy with best No values chemotherapy with best values values gastrointestinal cancer without best supportive care supportive care patients. supportive care Evaluation of clinical benefit of chemotherapy in patients Hoffman Best supportive Chemotherapy and best No No 1998 61,0 No differences in QoL with upper gastrointestinal K care suportive care values values cancer. FACULTY OF MEDICINE – UNIVERSITY OF PORTO Department of Biostatistics and Medical Informatics Introdução à Medicina 2005/2006

Randomized comparison between chemotherapy plus QoL increases in Glimelius Best supportive Chemotherapy and best No No best supportive care with 1997 55,0 chemotherapy with best B care suportive care values values best supportive care in supportive care advanced gastric cancer. Epirubicin, cisplatin, and protracted venous infusion Patients of 5-fluorouracil for submitted to a Patients submitted to a No No QoL increases in both esophagogastric Bamias A 1996 treatment with venous infusion of 5- No values values values groups adenocarcinoma: response, epirubicin and fluorouracil toxicity, quality of life, and cisplatin survival. A phase II study in advanced Patients submitted to a gastro-esophageal cancer Patients not treatment with epurubicin using epirubicin and Findlay 1994 submitted to the and cisplatin in 27,9 28,0 No values No differences in QoL cisplatin in combination with M treatment combination with infusion continuous infusion 5- 5-fluorouracil fluorouracil (ECF).

Discussion Although incidence of gastric carcinoma is on the decline, it remains the second most common cause of death from malignant diseases. Nevertheless, incidence rates differ from one geographical region to another, being rather high in Japan, China, Columbia, and Costa Rica, and comparatively low in the United States [122]. QoL should be measured by an adequate instrument. The proper instrument for this is a questionnaire. Nowadays, there are multiple options available to serve that purpose. Although, there are many aspects to consider when the time to choose arrives. The most important one is to make sure that the questionnaire chosen is the best for the group of people in study. Beside, the questionnaire should be validated, because that proves it’s reproducibility and guarantees that it is proper for the matter in study. 1. Articles Review

Having in mind the main aim of the current study -to assess QoL in patients treated with chemo and radiotherapy for gastric cancer- papers dealing with the theme were analysed. A great amount of information could not be used due to language limitations. Nowadays, Japan is the country most motivated to investigate this issue, wich is reflected in the number of papers published. This fact is understandable due to the high incidence of this disease in this country, although is important to mention it has been progressively decreasing [122]. From that analysis is possible to infer that the most part of the research made about this issue focus mainly surgery as a treatment. A fact that is understandable since surgery is FACULTY OF MEDICINE – UNIVERSITY OF PORTO Department of Biostatistics and Medical Informatics Introdução à Medicina 2005/2006 a potentially curative for this kind of pathology [26]. Beside, some articles found mentioned chemo and radiotherapy as treatment, but as an adjuvant therapy (after the patients were submitted to surgery). So it was impossible to distinguish if the differences in QoL results, before and after treatment, were due to chemo and radiotherapy, surgery, or both. Even the articles which refer chemo and radiotherapy as a single treatment, in many cases didn’t use a proper instrument for its measurement. Its major concern is to assess if the patients survival time has increased after treatment. There are also thirty six articles that only make the analysis of the patient’s symptoms; this does not clearly contribute to an assessment of QoL, as it is supposed to be measured as perceived by the patient. Other studies predict the survival time of the patients only. These articles weren’t used for this reason. In spite of the fact that all the included articles evaluated QoL with an adequate instrument, that measurement was merely qualitative; this clearly prevented us from going into a meta-analysis, which was the second goal of this work. 2. Limitations to our work After extract all the data necessary from the papers in study was possible to understand the impossibility to perform a meta-analysis. In spite of all the included articles have used a validated instrument to assess QoL, only a qualitative value was presented. Besides, the number of papers included was very small. It is yet impossible to determine a median value to QoL in patients treated with chemo and radiotherapy in gastric cancer. Is important to emphasise that scientists are trying to develop new combinations of drugs and test their effects. So, the main objective today is to realize what the best combination available is. From that point of view is understandable that the evaluation of QoL appears qualitatively because there are two drugs being compared. And the QoL of the patients differs from one combination to another. In future studies, the values obtained from the measure of QoL should be given as results, so readers could understand what “QoL increased when patients were treated with this combination” really means. With that kind of approach, those results could be used for further investigation. FACULTY OF MEDICINE – UNIVERSITY OF PORTO Department of Biostatistics and Medical Informatics Introdução à Medicina 2005/2006

3. Questionnaires Description - EORTC (European Organisation for Research and Treatment of Cancer) QLQ-C30 The 30-item Quality-of-Life Questionnaire-Cancer (QLQ-C30) is a multidimensional self-report measure of quality of life designed for use with clinical trials [124]. It reports functional (physical, role, social, cognitive, and emotional) and financial aspects of QoL as well as symptoms, global health, and global quality of life. Items are scaled from 0 (lowest on functional and symptom items) to 100 (best functioning but most symptoms). This questionnaire is translated into other languages. Validity was evaluated with 305 patients in 13 countries. Generally 11 minutes are needed to complete the questionnaire [123]. This instrument is validated [125]. - RSCL (Rotterdam Symptom Checklist) The 30-item Rotterdam Symptom Checklist is a Cancer-specific questionnaire to measure psychological and physical distress in cancer patients participating in clinical research. Patients are asked to indicate the degree to which they have been bothered by the indicated symptoms in the past week. Over the last years RSCL has been used in numerous studies of oncology. This questionnaire is validated and available in other languages [126] [127]. - HADS (Hospital Anxiety and Depression Scale) The 14-item Hospital Anxiety and Depression Scale questionnaire is a self screening questionnaire for depression and anxiety [128]. It reports seven items for anxiety and seven for depression. The patients shouldn’t take too long giving their replies: their immediate reaction to each item will probably be more sincere.

4. Questionnaires review Nowadays, chemo and radiotherapy given at an advanced stage of gastric cancer (often metastic), when they are not combined with other treatments, are considered palliative treatments [75]. Patients studied in the selected papers are at a final stage. The review we carried on indicates that the used questionnaires have not been exclusively conceived to be applied to palliative patients. In fact, many of the items (questions or statements) aren’t appropriate to these patients and are totally disconnected from their FACULTY OF MEDICINE – UNIVERSITY OF PORTO Department of Biostatistics and Medical Informatics Introdução à Medicina 2005/2006 real health condition. Here are some of the questions we found: “Do you have any trouble doing strenuous activities, like carrying a heavy shopping or a suitcase?”, “Do you have any trouble taking a long walk?”, “Where you limited in doing your work or other daily activities?”, “Where you limited in pursing your hobbies or other leisure time activities?” [EORTC QLQ-C30]; “Lack of sexual interest” was also mentioned [Rotterdam symptom checklist]. Being palliative patients, their scale of QoL should probably be different from the one conceived for a patient with gastric cancer at an early stage. In fact, the latter still have other optional treatments and their QoL can still be compared to the one of someone who doesn’t suffer from this kind of pathology. 5. Questionnaires to be applied in patients under palliation Another finding of this review showed that there are validated questionnaires proper to palliative patients, available in several languages. Despite, neither of them achieved the status of being a generally recommended instrument. These have more adequate questions, like: “Approximately how many hours per day (8 a.m. to 8 p.m.) have you been lying down?”, “How much help have you needed with dressing and hygiene?”, “How much pain have you had last week?” and “How many days during the past week have you spent in a hospital/nursing home?” [The AQEL questionnaire for assessment of patient’s quality of life in palliative care] [123]. The time frame chosen for the questions is often one to few weeks ago since this type of patients nearing the end of life can have “good” days and “bad” days alternatively. Therefore, a time frame of one or a few days may by chance cover only one extreme [123]. Besides, the ideal response format has verbal extreme values, for example, 1 is defined as “no pain” and 10 as the “worst possible pain”. This choice is based on the literature [123] and makes the assisted completion easier in case of patients that are too weak to hold the pencil. The items should represent physical, psychological, social, existential, global aspects of quality of life and accessibility of medical care [123] [129]. - AQEL (Assessment of Quality of life at the End of Life) The 36-item Assessment of Quality of life at the End of Life questionnaire was made to assess patient's quality of life in palliative care. Their items are divided by the mode of administration: 19+3 (complementary questions) self administered and 14 proxy- administered (spouse). They measure the physical, psychological, social, existential, FACULTY OF MEDICINE – UNIVERSITY OF PORTO Department of Biostatistics and Medical Informatics Introdução à Medicina 2005/2006 and global aspects of quality of life. Their main headings are pathologies connected with neoplasms. It’s only available in English and Swedish [123]. This instrument is validated [123]. - EORTC (European Organisation for Research and Treatment of Cancer) QLQ-C15-PAL The 15-item EORTC QLQ-C15-PAL is a questionnaire developed to assess the quality of life of palliative care cancer patients. Depending on the type of study in question, it may be supplemented by additional items, modules or questionnaires [130]. The QLQ- C15-PAL includes those elements of the QLQ-C30 identified as most relevant and important for palliative care, i.e., physical and emotional function, pain, fatigue, nausea/vomiting, appetite, dyspnoea, constipation, sleeping difficulties, and overall QoL. The QLQ-C15-PAL is recommended for use in patients with advanced, incurable, and symptomatic cancer with a median life expectancy of a few months. However, this instrument isn’t recommended for patients receiving palliative, anti-cancer treatments including chemotherapy, radiotherapy, endocrine treatments, or palliative surgery. These patients generally have a better prognosis and are able to complete the EORTC QLQ- C30 [129]. This is a validated questionnaire [130]. - PQLI (Palliative Care Quality of Life Instrument) The 28-item Palliative Care Quality of Life Instrument is a reliable and valid measure for the assessment of quality of life in patients with advanced stage cancer. It’s a questionnaire composed by six multi-item scales (two functional scales, one symptom scale, one choice of treatment scale and one psychological scale) and a single item scale (overall quality of life). The average time required to complete the questionnaire is approximately 8 minutes [131]. This is a validated questionnaire [131]. - FLIC (Functional Living Index Cancer) The 22-item Functional Living Index Cancer questionnaire is a cancer-specific, functionally-oriented quality of life instrument. Their categories are: physical well- being and ability, emotional state, sociability, family situation and nausea. This questionnaire allows assessing the effect of the symptoms of cancer and its treatment on functional ability in all areas of life. The questionnaire is completed in less than ten FACULTY OF MEDICINE – UNIVERSITY OF PORTO Department of Biostatistics and Medical Informatics Introdução à Medicina 2005/2006 minutes and is available in other languages [131]. This is a validated questionnaire [132] [133]. - McGill Quality of Life Questionnaire The 16-item McGill Quality of Life Questionnaire is designed specifically to measure quality of life for people with life-threatening illness. This instrument is acceptable to oncology outpatients [134]. Four subscales were identified through factor analysis: physical symptoms, psychological symptoms, outlook on life, and meaningful existence. Both the sub-scale scores and the overall score can range from 0 to 10, facilitating the identification of specific domains that need attention relative to overall quality of life. This questionnaire differs from most others in three ways: the existential domain is measured; the physical domain is important but not predominant; positive contributions to quality of life are measured. It is available in many languages and takes between 10 and 30 minutes to be completed [135]. This questionnaire is validated [136]. - POS (Palliative Care Outcome Scale) The 12 item Palliative Care Outcome Scale questionnaire was made to help clinical practitioners meet people's palliative care needs. It’s applied to terminal patients with generic neoplasms. It is a multidimensional instrument covering physical, psychosocial, spiritual, organizational, and practical concerns. Generally, this questionnaire is well accepted by the patients and their questions are understandable. This is a validated instrument, available in other languages [137]. 6. Final remarks There are many differences between a patient with gastric cancer in an early stage and in an advanced stage. Nowadays, there are questionnaires specific to terminal patients. In the present study we’ve described some of the validated options available. It isn’t clear yet witch one is the best option, but is extremely important that investigators start to apply the same questionnaire. Only with a unique scale it is possible to clarify the results obtained trough the different papers. The differences in the questionnaires are particularly clear in the physical and emotional dimensions, witch is understandable, given the limitations of each stage. Nowadays, only a few papers focus only the advanced stage of gastric cancer. Generally a study that mentions chemo and radiotherapy as the only treatment, also studies the FACULTY OF MEDICINE – UNIVERSITY OF PORTO Department of Biostatistics and Medical Informatics Introdução à Medicina 2005/2006 other treatments and consequently, every stages of the disease. That isn’t the best approach, since the most adequate instruments are not the same to every stage. Ideally there would be studies only about patients in an advanced stage of the disease, since the most adequate instruments are not the same. When that is not possible, more than one kind of instrument should be used, in order to achieve better conclusions. The main concern of the studies that focus this stage of the disease is the survival time of the patients submitted to the different treatments. Beside, there isn’t agreement if chemo and radiotherapy treatments are better than supportive care alone. QoL is still a minor issue, what is intriguing since these patients have the pathology in an incurable stage; so, provide them the best QoL possible should be the major objective of the medical care. From that point of view, assess QoL is essential to help physicians choosing the treatment for their patients. In many cases, only an analysis of the changes in physic symptoms is carried on (a task that any physician can perform): The patient should be perceived as a person in every dimensions of the concept. So, QoL needs to be determined covering as many aspects of that concept (not only the physical condition), using the most accurate instrument as possible. And we must not forget that QoL just makes sense only when evaluated by the person. Acknowledgments We acknowledge to Professor Dr. Altamiro da Costa Pereira for the helpful commentaries. They really contributed for us to perform it better. We are also very grateful to Professor Dr. Mário Dinis Ribeiro and Dr. Camila for the continuous help given through this year. Not forgetting all the authors that have promptly furnished the articles necessary for the success of our work.

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