Cancer-associated Symptoms Research Articles

Cancer and systemic inflammation: treat the tumour and treat the host

Determinants of cancer progression and survival are multifactorial and host responses are increasingly appreciated to have a major role. Indeed, the development and maintenance of a systemic inflammatory response has been consistently observed to confer poorer outcome, in both early and advanced stage disease. For patients, cancer-associated symptoms are of particular importance resulting in a marked impact on day-to-day quality of life and are also associated with poorer outcome. These symptoms are now recognised to cluster with one another with anorexia, weight loss and physical function forming a recognised cluster whereas fatigue, pain and depression forming another. Importantly, it has become apparent that these symptom clusters are associated with presence of a systemic inflammatory response in the patient with cancer. Given the understanding of the above, there is now a need to intervene to moderate systemic inflammatory responses, where present. In this context the rationale for therapeutic intervention using nonselective anti-inflammatory agents is clear and compelling and likely to become a part of routine clinical practice in the near future. The published literature on therapeutic intervention using anti-inflammatory agents for cancer-associated symptoms was reviewed. There are important parallels with the development of useful treatments for the systemic inflammatory response in patients with rheumatological disease and cardiovascular disease.

Berberine enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in breast cancer

Berberine (BBR) has been used for the treatment of bacterial and fungal infections and also for cancer-associated symptoms such as diarrhea. Furthermore, it has been reported that BBR may have direct antitumor effects. Although evidence supports the theory that tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a promising candidate for treating cancer, its usage may be limited due to the resistance to the TRAIL-induced apoptosis of cancer cells. In the present study, the effect of BBR on TRAIL-induced antitumor effects was investigated in vitro using recombinant TRAIL and in vivo using a 4T1 murine breast cancer model in combination with anti-DR5 (death-inducing TRAIL receptor) monoclonal antibody therapy. BBR sensitized human breast cancer cell lines to TRAIL-mediated apoptosis in vitro. The combination of BBR and recombinant TRAIL significantly activated caspase-3 and PARP cleavage in TRAIL-resistant MDA-MB-468 cells. Furthermore, BBR in combination with TRAIL more effectively induced apoptosis compared with coptisine (COP), which is structurally related to BBR. In a murine 4T1 breast cancer model, BBR treatment enhanced the efficacy of anti-DR5 antibody therapy against primary tumor growth and lung metastasis. Thus, BBR may become a new adjuvant for overcoming the resistance of cancer cells to TRAIL/DR5-mediated therapy.

Lung Cancer and Paraneoplastic Neurologic Syndromes. Case Report and Review of the Literature

Address for correspondence: Dr Marco Rossato, MD, PhD, University of Padova, Department of Medicine, DIMED, Clinica Medica 3, 35128 Padova, Italy Clinical Pra ● Paraneoplastic syndromes refer to cancer-associated signs and symptoms arising in organs that are remote from the cancer and unrelated to metastases. ● Paraneoplastic neurological syndromes are rare, affecting only 0.01% of patients with cancer. About 3-5% of patients with small-cell lung cancer present paraneoplastic neurological syndromes. ● Generally paraneoplastic neurologic syndromes are due to the production of antibodies against neural antigens expressed by the tumor and that are present in normal neuronal tissues. ● Here we describe the case of a male patient with distal polyneuropathy due to production of auto-antibodies versus myelin associated glycoprotein (MAG) and nonsmall-cell lung cancer expressing MAG on cancer cells. ● The tumor and the immune system are both implicated in the development of paraneoplastic neurological syndromes that are generally thought to

Towards the use of cannabinoids as antitumour agents

Various reports have shown that cannabinoids (the active components of marijuana and their derivatives) can reduce tumour growth and progression in animal models of cancer, in addition to their well-known palliative effects on some cancer-associated symptoms. This Opinion article discusses our current understanding of cannabinoids as antitumour agents, focusing on recent insights into the molecular mechanisms of action, including emerging resistance mechanisms and opportunities for combination therapy approaches. Such knowledge is required for the optimization of preclinical cannabinoid-based therapies and for the preliminary clinical testing that is currently underway.

Yoga Breathing for Cancer Chemotherapy–Associated Symptoms and Quality of Life: Results of a Pilot Randomized Controlled Trial

Many debilitating symptoms arise from cancer and its treatment that are often unrelieved by established methods. Pranayama, a series of yogic breathing techniques, may improve cancer-related symptoms and quality of life, but it has not been studied for this purpose. A pilot study was performed to evaluate feasibility and to test the effects of pranayama on cancer-associated symptoms and quality of life. This was a randomized controlled clinical trial comparing pranayama to usual care. The study was conducted at a university medical center. Patients receiving cancer chemotherapy were randomized to receive pranayama immediately or after a waiting period (control group). The pranayama intervention consisted of four breathing techniques taught in weekly classes and practiced at home. The treatment group received pranayama during two consecutive cycles of chemotherapy. The control group received usual care during their first cycle, and received pranayama during their second cycle of chemotherapy. Feasibility, cancer-associated symptoms (fatigue, sleep disturbance, anxiety, depression, stress), and quality of life were the outcomes. Class attendance was nearly 100% in both groups. Sixteen (16) participants were included in the final intent-to-treat analyses. The repeated-measures analyses demonstrated that any increase in pranayama dose, with dose measured in the number of hours practiced in class or at home, resulted in improved symptom and quality-of-life scores. Several of these associations--sleep disturbance (p=0.04), anxiety (p=0.04), and mental quality of life (p=0.05)--reached or approached statistical significance. Yoga breathing was a feasible intervention among patients with cancer receiving chemotherapy. Pranayama may improve sleep disturbance, anxiety, and mental quality of life. A dose-response relationship was found between pranayama use and improvements in chemotherapy-associated symptoms and quality of life. These findings need to be confirmed in a larger study.

An Exploratory Pilot Study of Palliative Medicine Compared to Anesthesia–Pain Consultation for Pain in Patients with Cancer

Oncologists often manage cancer-associated symptoms including pain. When symptoms are severe, anesthesia-pain medicine (APM) and/or palliative medicine (PM) can effectively treat symptoms. Nevertheless, symptom management may be suboptimal, leading to diminished quality of life (QOL). We assessed the value of PM vs. APM consultation in cancer patients referred for pain management alone. Patients referred to an APM-based Cancer Pain Clinic (CPC) over an 8-month period were evaluated by PM or APM based on the first available appointment. Symptoms and QOL were assessed by the MD Anderson Symptom Inventory and Linear Analog Self-Assessment at baseline and 4-6 weeks after initial encounter. Data were analyzed on an available-case basis. Sixty-two patients (37 PM, 25 APM) completed the initial survey, with 48 patients (31 PM, 17 APM) completing followup. Mean pain score improved from 7.97 to 5.47 in the PM group (P < 0.0001) and from 7.1 to 4.5 (P = 0.29) in the APM group. The PM group demonstrated a clinically significant improvement in 8/19 symptoms vs. 3/19 in the APM group and in 3/5 QOL parameters in the PM group vs. 1/5 in the APM group. Our small sample size weakens our power and ability to detect significant differences between the groups. Only one follow-up symptom-assessment point was obtained. PM consultation is as effective as APM in improving cancer pain but may be more effective with symptom management and improving QOL.

An exploratory pilot study of palliative medicine versus anesthesia-pain consultation for cancer pain.

e19564 Background: Cancer-associated symptoms may be well managed by oncologists, though anesthesia-pain medicine (APM) and/or palliative medicine (PM) possess expertise in assessing and treating difficult symptoms. We compared PM vs. APM consultation in patients referred for “cancer pain management.” Methods: Patients referred to Anesthesia Cancer Pain Clinic over an 8-month period were evaluated by PM or APM randomly based on provider availability. PM and APM groups at baseline were comparable. Surveys including MD Anderson Symptom Inventory (MDASI) and Linear Analog Self Assessment were completed by all patients at baseline. Surveys were used by PM providers to assist with symptom and quality of life (QOL) assessment and treatment planning, but were not reviewed by APM providers. Follow up survey was completed by patients in person or by telephone 4-6 weeks after initial encounter as able. Data were analyzed on available-case basis with Wilcoxon Rank Sum test. Results: Sixty-two patients (37 PM, 25 APM, median age 61.2 y) completed initial survey with 48 (31 PM, 17 APM) completing follow up survey (6 unavailable, others expired—median survival 29 d). Mean pain score improved from 8 to 5.4 in PM group (P<0.001), 7.1 to 5.4 in the APM group (p<0.28). Disturbed sleep, anorexia, and mood showed statistically significant improvement in PM group, while others had a trend toward significance. Between PM and APM, a trend toward statistical significance was noted in nausea, disturbed sleep, and walking. PM demonstrated clinical significance (minimal important difference for MDASI = 1.2 point change) with 9/19 symptoms (PM) vs. 2/19 (APM). Twenty-four of 62 patients have since died with median survival 44 d. Conclusions: Cancer patients experience multiple symptoms including pain that adversely impact QOL. Though exploratory in design, these data suggest cancer pain and symptoms, QOL, and goals of care not requiring procedural intervention may be best suited for PM consultation over APM. Collective mortality in both groups was 39% at 157 d (range 6-157 d), suggesting poor prognosis in referred patients. Misconceptions of what PM entails may affect referral pattern; educational efforts are ongoing. No significant financial relationships to disclose.

Evidence-Based Recommendations for Cancer Fatigue, Anorexia, Depression, and Dyspnea

PURPOSE The experience of patients with cancer often involves symptoms of fatigue, anorexia, depression, and dyspnea. METHODS We developed a set of standards through an iterative process of structured literature review and development and refinement of topic areas and standards and subjected recommendations to rating by a multidisciplinary expert panel. Results For fatigue, providers should screen patients at the initial visit, for newly identified advanced cancer, and at chemotherapy visits; assess for depression and insomnia in newly identified fatigue; and follow up after treatment for fatigue or a secondary cause. For anorexia, providers should screen at the initial visit for cancer affecting the oropharynx or gastrointestinal tract or advanced cancer, evaluate for associated symptoms, treat underlying causes, provide nutritional counseling for patients undergoing treatment that may affect nutritional intake, and follow up patients given appetite stimulants. For depression, providers should screen newly diagnosed patients, those started on chemotherapy or radiotherapy, those with newly identified advanced disease, and those expressing a desire for hastened death; document a treatment plan in diagnosed patients; and follow up response after treatment. For general dyspnea, providers should evaluate for causes of new or worsening dyspnea, treat or symptomatically manage underlying causes, follow up to evaluate treatment effectiveness, and offer opioids in advanced cancer when other treatments are unsuccessful. For dyspnea and malignant pleural effusions, providers should offer thoracentesis, follow up after thoracentesis, and offer pleurodesis or a drainage procedure for patients with reaccumulation and dyspnea. CONCLUSION These standards provide a framework for evidence-based screening, assessment, treatment, and follow-up for cancer-associated symptoms.

Early clinical detection of ovarian cancer: a review of the evidence

Subjective and objective evidence suggest that a third to half of patients developing ovarian cancer report symptoms at 3 or more months prior to diagnosis. Early ovarian cancer-associated symptoms constitute a constellation of mostly nongynecological complaints, suggesting a visceral disturbance, which do not point immediately to a pelvic origin. Abdominal bloating and pain predominate with recent onset and multiple symptomatic episodes. Gastrointestinal and urinary symptoms and fatigue/malaise may be part of the symptom complex. Women aged 50 years and older with this constellation of symptoms should have medical evaluation and, if symptoms are unexplained or persist, should undergo pelvic imaging (e.g., transvaginal ultrasound) and serum CA125.

Regression of chemotherapy-refractory metastatic tumor from CD117-negative prostate sarcoma with imatinib mesylate plus thalidomide

9557 Background: Chemoresistant relapsing prostate sarcoma has no standard treatment and the prognosis is extremely poor. Imatinib mesylate may target on tyrosine kinases of platelet-derived growth factor receptor (PDGFR) which has been shown to be important in tumor growth of certain types of soft tissue sarcoma. Thalidomide, itself a potent immunomodulatory agent has exhibited clinical activity in several malignant neoplasms which have been linked to abnormal angiogenesis and tumor vasculature. Case Report: A 38-year-old man who underwent radical cystoprostatectomy in June 2004 for a stage III high-grade soft tissue sarcoma of spindle and round cell type of prostate staged pT2b(8cm) pN0(0/26) M0, received adjuvant radiotherapy up to 6,660 cGy/37Fx postoperatively. Immunohistochemistry study showed vimentin+, CD34+, CD117−, desmin+, SMActind- and S-100−. Distant relapse in lungs was noted in April 2005. Shortly later massive pleural effusion developed. Three cycles of salvage chemotherapy with MAID were given. Tumor assessment disclosed Progressive Disease status and metastatic tumors were chemoresistant. Imatinib mesylate 400 mg once a day plus thalidomide with increment dose to 200 mg/day was chosen as biologic treatment for his devastating condition after an informed consent was obtained. PDGFR immunohistochemistry staining of the paraffin block and gene sequencing are planned. Results: Marked tumor regression reaching very good partial remission and resolution of pleural effusion without recurrence. Dramatic improvement in terms of performance status and cancer-associated symptoms are obvious. Except for skin changes and mild periorbital edema from imatinib, no other significant adverse reactions were noted. Postulated mechanism of action may suggest PDGFR tyrosine kinase inhibition as well as antiangiogenesis. Conclusions: We documented a case of undifferentiated sarcoma of prostate with pulmonary metastases which were refractory to MAID chemotherapy but subsequently regressed on a combination of double biologic agents, imatinib mesylate plus thalidomide. No significant financial relationships to disclose.

The impact of ”laying on of hands” on well being in patients with advanced cancer

18566 Background: To determine whether the impact of “laying on of hands” on well being of patients with advanced cancer is more efficient when performed by a person with “healing powers” as compared to an actor. Methods: A total of 80 patients was registered to participate in a randomized, single-blind phase III trial to evaluate the difference in efficacy of “laying on of hands” by either a “healer” or a sham person (actor). Both arms were designed to consist of a total of 40 patients, divided into 5 groups including 8 patients each. Each patient should receive treatment for 5 minutes, 3 times a week. A “Well-being scale” was used to measure differences in treatment outcomes. The primary and secondary endpoint evaluated the difference in the total sum score of the “Well-being scale” between the two arms on day 10 or day 5, respectively. Results: The first run was unblinded by the “healer”. Hence, only the second run was available for comparison. There was no significant difference in sum-score values between the “healer” and the actor (p = 0.34) with regard to the primary endpoint or the secondary endpoint (p = 0.94). After the second run, the “healer” quit and a major protocol violation occurred. Despite this major obstacle, the study was completed by the actor as a descriptive, explorative study. There was a significant decrease in total sum score values after each single treatment (day 1, 3 and 5, p &lt; 0.0001, respectively) for all patients. In addition, a significant improvement in symptoms could be found on day 5 (p &lt; 0.001) after treatment and day 10 (p = 0.0002) as compared to day 1 before treatment. Conclusions: “Laying on of hands” resulted in a significant improvement of cancer or cancer-therapy associated symptoms. The magnitude of improvement obtained was similar when “treatment” was provided by a self declared “healer” or an actor, although the comparison was hampered by protocol vialotions by the “healer”. No significant financial relationships to disclose.

Patient Appointment Process, Symptom Control and Prediction of Follow-up Compliance in a Palliative Care Outpatient Clinic

Activities and outcomes in an outpatient palliative care clinic (PCC) have attracted little attention in the literature. We describe the results of our patient appointment scheduling process, our efficacy in relieving cancer-associated symptoms and an analysis of risk factors for patient non-compliance with the appointment schedule. Over a one-year study period, 730 first-time appointments were scheduled and 73.1% of them were kept. Only patients who had kept 3 consecutive visits (n = 203) were included in the symptom control analysis. All symptoms except constipation, physical weakness, and anxiety improved significantly with palliative care. History of alcohol abuse was not associated with poorer pain control. A low Karnofsky index and high anxiety levels were identified as risk factors for early withdrawal from the PCC scheduled appointment. These data indicate that the PCC is an effective place for symptom management, but specific organizational strategies are needed to encourage patients to comply with scheduled appointments.

Importance of cancer-associated symptoms on prognosis of patients with metastatic renal cell carcinoma: A single-center experience

4801 Background: Metastatic renal cell carcinoma (mRCC) has a poor prognosis, but survival is quite different among different subgroups of patients, it doesn’t matter how they were treated. Some clinical and biochemical prognostic factors have been published. Objective: To evaluate the prognostic impact of cancer - related symptoms present at the diagnosis of mRCC. Methods: We analyzed the clinical records of patients with histologically confirmed mRCC who have been seen in our center from January 2000 to May 2004. Results: 43 patients with mRCC, 29 men and 14 female, the median age was 57 years (39–78y), the most common sites of metastases were bone (33%), lung (32%), retroperitoneal nodes (23%), liver (18%), brain (9%), soft tissue (9%) and other (<5%), most of the patients had two or more sites of metastases. 10/43 patients (23.2%), were asymptomatic at the diagnosis. 27 patients received specific oncologic treatment (immunotherapy, RT,CH) and 16 only symptomatic medication. 30 patients have died (69.7%). The median survival was 22 months in patients who were asymptomatic and 6.3 months in patients with symptoms (ECOG >1) at the diagnosis. 8/13 patients alive were asymptomatic at the diagnosis, their median survival is 23.7 months and only 4 (50%) received specific treatment (3RT,1CH). Conclusions: mRCC has an unpredictable evolution, only a minority of treated patients experience a favorable response with “standard” therapy, patients who are symptomatic at the diagnosis have the poorest survival, performance status (ECOG) is the strongest prognostic factor. No significant financial relationships to disclose.

N-3 Polyunsaturated fatty acids throughout the cancer trajectory: influence on disease incidence, progression, response to therapy and cancer-associated cachexia

Evidence from epidemiological studies suggests that diets rich in n-3 PUFA may be associated with reduced cancer risk. These observations have formed the rationale for exploring the mechanisms by which n-3 PUFA may be chemoprotective and have resulted in significant advances in our mechanistic understanding of n-3 PUFA action on tumour growth. Various interrelated and integrated mechanisms may be at work by which n-3 PUFA influence cancer at all stages of initiation, promotion, progression, and neoplastic transformation. More recently, experimental studies have reported enhanced tumour cell death with chemotherapy when fish oil is provided while toxic side effects to the host are reduced. Furthermore, cancer-associated wasting has been shown to be attenuated by fish oil supplementation. Clinical evidence suggests that the n-3 PUFA status of newly diagnosed cancer patients and individuals undergoing chemotherapy is low. Therefore, both the disease itself and therapeutic treatments may be contributing factors in the decline of n-3 PUFA status. Dietary supplementation to maintain and replenish n-3 PUFA status at key points in the cancer disease trajectory may provide additional health benefits and an enhanced quality of life. The present review will focus on and critically examine current research efforts related to the putative anti-cancer effects of n-3 PUFA and their suggested ability to palliate cancer-associated and treatment-associated symptoms.

Impact of tumor-associated symptoms on the prognosis of patients with renal cell carcinoma: a single-center experience of 683 patients

Objectives To evaluate the impact of cancer-associated symptoms present at the diagnosis of renal cell carcinoma (RCC) on the prognosis of patients. Increasing numbers of RCC are currently detected incidentally by routine ultrasonography. Methods From January 1994 to December 2000, 693 operations for RCC in 683 consecutive patients have been performed at our institution. Overall, tumor-specific, and progression-free survival were investigated using the Kaplan-Meier method. For multivariate analysis regarding tumor-specific survival, the Cox regression model, including risk ratios, was used. A receiver operating characteristics curve regarding the sensitivity and specificity for the association between tumor size and symptoms was used. Results Of the 683 patients, 417 patients were male and 266 female. The mean patient age was 62 years (range 16 to 88). Of the 683 patients, 141 (20.8%) presented with symptoms suspicious for cancer. The 5-year overall, progression-free, and cancer-specific survival rates were 82%, 79%, and 86%, respectively, for asymptomatic patients compared with 60%, 55%, and 65%, respectively, for patients with symptoms at diagnosis ( P <0.0001, log-rank test). The cutoff value of 5 cm for the tumor diameter to result in symptoms was chosen on the receiver operating characteristic curve. Multivariate analysis found tumor grade ( P = 0.001), tumor stage ( P = 0.001), presence of symptoms ( P = 0.013), and tumor diameter ( P = 0.005) to be independent prognostic parameters for cancer-specific survival. Conclusions Tumors larger than 5 cm were significantly more likely to cause symptoms compared with smaller tumors in our series. In multivariate analysis, patients presenting with symptoms suspicious for cancer at the diagnosis of RCC had a 1.8-fold greater risk of dying of cancer compared with patients without symptoms.

Long-Term Safety and Clinical Effectiveness of Controlled-Release Metoclopramide in Cancer-Associated Dyspepsia Syndrome: A Multicentre Evaluation

Patients with cancer frequently report gastrointestinal symptoms such as anorexia, early satiety, nausea, vomiting, and bloating. A reduction of the severity of some of these symptoms would benefit the patient by enhancing quality of life and improving their treatment. Forty-eight patients (25 female and 23 male; mean age 63 +/- 11 years) with a minimum two-week history of cancer-associated gastrointestinal symptoms were assigned to a single, open-label treatment group and received controlled-release metoclopramide 20 mg-80 mg q12h for a maximum period of 12 weeks (mean 46 +/- 35 days). There was a 40%-60% decrease in the severity of nausea over the first two weeks of treatment, and an approximate 50% reduction in severity of vomiting over the first four weeks of treatment. Appetite and bloating also improved, although smaller and less consistent changes were observed. Patient ratings of overall clinical effectiveness with respect to relief from symptoms and tolerability of side effects indicated that controlled-release metoclopramide was highly and moderately effective in 36% and 30% of the patients, respectively. Controlled-release metoclopramide is a useful treatment for the management of gastrointestinal symptoms associated with the cancer-associated dyspepsia syndrome including nausea, vomiting, loss of appetite, and bloating.

The EORTC QLQ-LC13: A modular supplement to the EORTC core quality of life questionnaire (QLQ-C30) for use in lung cancer clinical trials: Bergman B, Aaronson NK, Ahmedzai S, Kaasa S, Sullivan M. Department of Pulmonary Medicine, Renstromska Hospital, P.O. Box 17301, S-402 64 Goteborg. Eur J Cancer Part A Gen Top 1994;30:635–642

The EORTC Study Group on Quality of Life has developed a modular system for assessing the quality of life of cancer patients in clinical trials composed of two basic elements: (1) a core quality of life questionnaire, the EORTC QLQ-C30, covering general aspects of health-related quality of life, and (2) additional disease- or treatment-specific questionnaire modules. Two international field studies were carried out to evaluate the practicality, reliability and validity of the core questionnaire, supplemented by a 13-item lung cancer-specific questionnaire module, the EORTC QLQ-LC13. In this paper, the results of an evaluation of the QLQ-LC13 are reported. The lung cancer questionnaire module comprises both multi-item and single-item measures of lung cancer-associated symptoms (i.e. coughing, haemoptysis, dyspnoea and pain) and side-effects from conventional chemo- and radiotherapy (i.e. hair loss, neuropathy, sore mouth and dysphagia). It was administered to patients with non-resectable lung cancer recruited from 17 countries. In total, 883 and 735 patients, respectively, completed the questionnaire prior to and once during treatment. The symptom measures discriminated clearly between patients differing in performance status. All item scores changed significantly in the expected direction (i.e. lung cancer symptoms decreased and treatment toxicities increased) during treatment. With one exception (problems with a sore mouth), the change of toxicity measures over time was related specifically to either chemo- or radiotherapy. However, the single item on neuropathy did not measure adequately the full range of symptoms. The hypothesised scale structure of the questionnaire was partially supported by the data. The multi-item dyspnoea scale met the minimal standards for reliability (Cronbach alpha coefficient > 0.70), while the pain items did not form a scale with reliability estimates acceptable for group comparisons. In conclusion, the results form international field testing lend support to the EORTC QLQ-LC13 as a clinically valid and useful tool for assessing disease- and treatment-specific symptoms in lung cancer patients participating in clinical trials, when combined with the EORTC core quality of life questionnaire. In a few areas, however, the questionnaire module could benefit from further refinements. In addition, its performance over a longer period of time still needs to be investigated.

The EORTC QLQ-LC13: a modular supplement to the EORTC core quality of life questionnaire (QLQ-C30) for use in lung cancer clinical trials

The EORTC Study Group on Quality of Life has developed a modular system for assessing the quality of life of cancer patients in clinical trials composed of two basic elements: (1) a core quality of life questionnaire, the EORTC QLQ-C30, covering general aspects of health-related quality of life, and (2) additional disease- or treatment-specific questionnaire modules. Two international field studies were carried out to evaluate the practicality, reliability and validity of the core questionnaire, supplemented by a 13-item lung cancer-specific questionnaire module, the EORTC QLQ-LC13. In this paper, the results of an evaluation of the QLQ-LC13 are reported. The lung cancer questionnaire module comprises both multi-item and single-item measures of lung cancer-associated symptoms (i.e. coughing, haemoptysis, dyspnoea and pain) and side-effects from conventional chemo- and radiotherapy (i.e. hair loss, neuropathy, sore mouth and dysphagia). It was administered to patients with non-resectable lung cancer recruited from 17 countries. In total, 883 and 735 patients, respectively, completed the questionnaire prior to and once during treatment. The symptom measures discriminated clearly between patients differing in performance status. All item scores changed significantly in the expected direction (i.e. lung cancer symptoms decreased and treatment toxicities increased) during treatment. With one exception (problems with a sore mouth), the change of toxicity measures over time was related specifically to either chemoor radiotherapy. However, the single item on neuropathy did not measure adequately the full range of symptoms. The hypothesised scale structure of the questionnaire was partially supported by the data. The multi-item dyspnoea scale met the minimal standards for reliability (Cronbach α coefficient >0.70), while the pain items did not form a scale with reliability estimates acceptable for group comparisons. In conclusion, the results from international field testing lend support to the EORTC QLQ-LC13 as a clinically valid and useful tool for assessing disease- and treatment-specific symptoms in lung cancer patients participating in clinical trials, when combined with the EORTC core quality of life questionnaire. In a few areas, however, the questionnaire module could benefit from further refinements. In addition, its performance over a longer period of time still needs to be investigated.