The Palliative Radiotherapy and Inflammation Study (PRAIS) - protocol for a longitudinal observational multicenter study on patients with cancer induced bone pain

BackgroundRadiation therapy (RT) results in pain relief for about 6 of 10 patients with cancer induced bone pain (CIBP) caused by bone metastases. The high number of non-responders, the long median time from RT to pain response and the risk of adverse effects, makes it important to determine predictors of treatment response. Clinical features such as cancer type, performance status and pain intensity, and biomarkers for osteoclast activity are proposed as predictors of response to RT. However, results are inconsistent and there is a need for better predictors of RT response. A similar argument can be stated for the development of cachexia; there are currently no predictors that can identify patients who will develop cachexia later in the cancer disease trajectory. Experimental and preclinical studies show that pain, depression and cachexia are related to inflammation. However, it is not known if inflammatory biomarkers can predict CIBP, depression or development of cachexia.MethodsThis multicenter, multinational longitudinal observational study will include 600 adult patients receiving RT for CIBP. Demographic data, clinical variables, osteoclast and inflammatory biomarkers will be assessed before start of RT, and 3, 8, 16, 24 and 52 weeks after last course of RT. The primary aim of the study is to identify potential predictors for pain relief from RT. Secondary aims are to explore potential predictors for development of cachexia, the longitudinal relationship between pain intensity and depression, and if inflammatory biomarkers are associated with changes in pain intensity, cachexia and depression during one-year follow up.DiscussionThe immediate clinical implication of the PRAIS study is to identify potential predictive factors for a RT response on CIBP, and thereby reduce non-efficacious RT. Patient benefits are fewer hospital visits, reduced risk of adverse effects and more individualized pain treatment. The long-term clinical implication of the PRAIS study is to improve the knowledge about inflammation in relation to CIBP, cachexia and depression and potentially identify associations and mechanisms that can be targeted for treatment.Trial registrationClinicalTrials.gov NCT02107664, date of registration April 8, 2014 (retrospectively registered).Trial sponsorThe European Palliative Care Research Centre (PRC), Department of Clinical and Molecular Medicine, NTNU, Faculty of medicine and Health Sciences, Trondheim, N-7491, Norway

Endpoints in clinical trials in cancer cachexia: where to start?

Purpose of review The lack of agreement and knowledge of optimal endpoints in cachexia trials have impeded progress in finding interventions counteracting the devastating effects cancer cachexia has on morbidity and mortality. An endpoint should both be sensitive enough to detect change and specific enough not to be influenced by other conditions or treatments. Recent findings There is a wealth of potential and applied endpoints in trials investigating cachexia. As of today, there is no generally acknowledged consensus, but assessments of key factors such as body composition should continue to be applied. However, the impact and effect size necessary to achieve clinical benefit using these endpoints are not clear. Further, the use of other endpoints assessing physical function, symptom evaluation and quality of life remains to be elucidated. Summary It is essential that endpoints are clinically relevant and further research is therefore needed to develop endpoints that are meaningful for patients with cachexia

Patient interpretation of the Patient-Generated Subjective Global Assessment (PG-SGA) Short Form

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Associations between hematologic toxicity and health-related quality of life during first-line chemotherapy in advanced non-small-cell lung cancer: a pooled analysis of two randomized trials

Background: Many patients experience toxicity from chemotherapy that may negatively impact their health-related quality of life (HRQoL), but side effects often go undetected by health care personnel. Our aim was to investigate whether hematologic toxicity (HT) was associated with HRQoL impairment, and, consequently, if blood counts could be used to identify patients with the highest need for supportive care during chemotherapy. Material and methods: Data from two phase III trials of first-line chemotherapy in advanced non-small-cell lung cancer (NSCLC) were analyzed (n = 873). Blood counts were measured weekly in the treatment period. We categorized patients as having severe (CTCAE grade 3–4) or non-severe (grade 0–2) HT during the first chemotherapy cycle. HRQoL was reported on the EORTC QLQ-C30 and LC13 before and at the end of the cycle. The primary endpoints were changes in global quality of life, fatigue, nausea/vomiting and dyspnea (LC13). Results: Of the 766 patients with complete data set, 177 (23%) developed severe HT during the first chemotherapy cycle. Changes in fatigue and nausea/vomiting were significantly worse for patients experiencing severe compared to patients with non-severe HT (difference in mean change of 4.9 points; p = .01, and 6.4 points; p = .01, respectively), but this association was limited to neutropenia, not thrombocytopenia or anemia. There were no significant associations between HT and global quality of life or dyspnea (difference in mean change of 2.1 points; p = .28, and 3.3 points; p = .053, respectively). Conclusions: Patients developing severe HT had worse changes in two out of four of the primary HRQoL endpoints, but the association was not strong enough to use blood counts to identify patients who need more clinical attention and supportive care during chemotherapy

Dietary treatment of weight loss in patients with advanced cancer and cachexia: A systematic literature review

Purpose A systematical literature review evaluating the effect of dietary counseling in treating weight loss and improving energy intake in patients with advanced cancer with different stages of cachexia. Principal results Five publications were retrieved, of which three were randomized. Two out of five studies showed less weight loss with dietary counseling (+1% weight gain vs. −1.5% weight loss, p = 0.03, 1.4 kg vs. −2 kg, p < 0.05), two presented positive effect on energy intake (92% of total caloric need vs. 73%, p < 0.01, 1865 ± 317 kcal vs. 1556 ± 497 kcal, ns). Conclusion Dietary counseling can effect energy intake and body weight, however, apparent heterogeneity between studies is present. Based on these results there is not enough proof of evidence that dietary counseling given to patients with cancer is beneficial for improving weight or energy balance in the different cachexia stages. Nutrition is an essential part of cachexia treatment as it is not considered possible to increase or stabilize weight if nutritional needs are not met

Patient interpretation of the Patient-Generated Subjective Global Assessment (PG-SGA) Short Form

Background: The Patient-Generated Subjective Global Assessment (PG-SGA) is a patient-reported instrument for assessment of nutrition status in patients with cancer. Despite thorough validation of PG-SGA, little has been reported about the way patients perceive, interpret, and respond to PG-SGA. The aim of this study was to investigate how patients interpret the patient-generated part of the PG-SGA, called PG-SGA Short Form. Methods: Purposive sampling was used to identify participants that had experienced weight loss and/or reduced dietary intake and/or had a low body mass index. Data were collected from 23 patients by combining observations of patients filling in the PG-SGA Short Form, think-aloud technique and structured interviews, and analyzed qualitatively using systematic text condensation. Results: Most of the participants managed to complete the PG-SGA Short Form without problems. However, participant-related and questionnaire-related sources of misinterpretation were identified, possibly causing misinterpretations or wrong/missing answers. Participants either read too fast and skipped words, or they struggled to find response options that were suitable for covering their entire situation perfectly. The word “normal” was perceived ambiguous, and the word “only” limited the participants’ possibility to accurately describe their food intake. Long recall periods in the questions and two-pieced response options made it difficult for patients to select only one option. Conclusion: The results of this study provide a unique patient perspective of using the PG-SGA Short Form and valuable input for future use and revisions of the form. The identified sources of misunderstanding could be used to develop a standardized instruction manual for patients and health care personnel using the PG-SGA Short Form

Patient interpretation of the Patient-Generated Subjective Global Assessment (PG-SGA) Short Form

Background: The Patient-Generated Subjective Global Assessment (PG-SGA) is a patient-reported instrument for assessment of nutrition status in patients with cancer. Despite thorough validation of PG-SGA, little has been reported about the way patients perceive, interpret, and respond to PG-SGA. The aim of this study was to investigate how patients interpret the patient-generated part of the PG-SGA, called PG-SGA Short Form. Methods: Purposive sampling was used to identify participants that had experienced weight loss and/or reduced dietary intake and/or had a low body mass index. Data were collected from 23 patients by combining observations of patients filling in the PG-SGA Short Form, think-aloud technique and structured interviews, and analyzed qualitatively using systematic text condensation. Results: Most of the participants managed to complete the PG-SGA Short Form without problems. However, participant-related and questionnaire-related sources of misinterpretation were identified, possibly causing misinterpretations or wrong/missing answers. Participants either read too fast and skipped words, or they struggled to find response options that were suitable for covering their entire situation perfectly. The word “normal” was perceived ambiguous, and the word “only” limited the participants’ possibility to accurately describe their food intake. Long recall periods in the questions and two-pieced response options made it difficult for patients to select only one option. Conclusion: The results of this study provide a unique patient perspective of using the PG-SGA Short Form and valuable input for future use and revisions of the form. The identified sources of misunderstanding could be used to develop a standardized instruction manual for patients and health care personnel using the PG-SGA Short Form

Combining optimal nutrition and exercise in a multimodal approach for patients with active cancer and risk for losing weight: Rationale and practical approach

Weight loss and functional decline is a common and detrimental consequence of cancer. The interventions that are offered to patients with weight loss and functional decline often seem haphazard and varying from center to center. The lack of stringent management is probably based both on lack of knowledge of existing treatment guidelines and the current weak level of evidence of clinical effects of different nutritional and exercise interventions. Some studies evaluated multimodal interventions with various treatment combinations, including nutrition and exercise, that report clinically significant effects on cachexia outcomes. As of today, however, there is a paucity of large randomized controlled trials that incorporate both a fully structured exercise program and a well-described nutritional intervention. Studies investigating combinations of several interventions in patients with active cancer and risk for losing weight are too few and too heterogeneous to enable firm conclusions about effect, optimal dose, or timing of interventions. However, data presented in this review suggest an overall benefit, especially if interventions are started before weight loss and loss of function become too severe. Thus, the aim of this review was to examine the evidence for combined treatments targeting weight loss in cancer patients

Dietary treatment of weight loss in patients with advanced cancer and cachexia: A systematic literature review

Purpose: A systematical literature review evaluating the effect of dietary counseling in treating weight loss and improving energy intake in patients with advanced cancer with different stages of cachexia. Principal results: Five publications were retrieved, of which three were randomized. Two out of five studies showed less weight loss with dietary counseling (+1% weight gain vs. −1.5% weight loss, p = 0.03, 1.4 kg vs. −2 kg, p < 0.05), two presented positive effect on energy intake (92% of total caloric need vs. 73%, p < 0.01, 1865 ± 317 kcal vs. 1556 ± 497 kcal, ns). Conclusion: Dietary counseling can effect energy intake and body weight, however, apparent heterogeneity between studies is present. Based on these results there is not enough proof of evidence that dietary counseling given to patients with cancer is beneficial for improving weight or energy balance in the different cachexia stages. Nutrition is an essential part of cachexia treatment as it is not considered possible to increase or stabilize weight if nutritional needs are not met