Background
Application of patient-reported outcomes (PROs) in surgical oncology has been limited because of patient heterogeneity. We analyzed symptom trajectories and their associations with ...recovery outcomes after lung cancer surgery, aiming to profile the heterogeneity of patients’ experiences and to identify patients needing extensive care.
Methods
Symptoms were assessed with the MDASI-LC before surgery, daily after surgery in hospital and weekly within 1 month after discharge. Patients were clustered based on symptoms from post-operative day 1 (POD1) to POD5, using the latent-class-trajectory-model. Functional recovery was compared across the trajectories. Logistic regression was used to explore risk factors for trajectories of more severe symptoms.
Results
Based on the five most severe post-surgery symptoms (pain, fatigue, coughing, shortness of breath, and disturbed sleep), we identified three distinct symptom trajectories among 424 patients mild,
N
= 225 (53.07%); severe-to-mild,
N
= 86 (20.28%); severe,
N
= 104 (24.53%). At discharge, more ‘severe’ patients (73.96%) did not achieve a functional recovery compared with those in mild (32.54%,
P
< 0.0001) or severe-to-mild (56.96%,
P
= 0.0274) groups. Factors of significant symptom increase on POD1 were younger-than-55 (OR = 1.94 95% CI 1.30–2.93,
P
= 0.001), undergoing open or multi-port video-assisted thoracoscopic surgery (OR = 1.59 95% CI 1.05–2.41,
P
= 0.03), and using two chest tubes (OR = 1.72 95% CI 1.12–2.65,
P
= 0.01). For patients experiencing dramatic symptom increase on POD1, older age (OR = 2.51 95% CI 1.40–4.59,
P
= 0.002) was associated with ‘severe’ trajectory.
Conclusions
This study demonstrated that PRO measures were capable of profiling heterogeneous symptom trajectories after lung cancer surgery. Those in-hospital trajectories were able to differentiate patients’ responses to treatments and signal the needs for extensive post-discharge care.
We hypothesized that patients with oropharyngeal cancer treated with intensity modulated proton therapy (IMPT) would have lower symptom burdens, as measured by patient-reported outcome (PRO) surveys, ...than patients treated with intensity modulated photon therapy (IMRT).
Patients were treated for oropharyngeal cancer from 2006 to 2015 through prospective registries with concurrent chemotherapy and IMPT or chemotherapy and IMRT and completed the MD Anderson Symptom Inventory for Head and Neck Cancer (MDASI-HN) module at various times before treatment (baseline), during treatment (acute phase), within the first 3 months after treatment (subacute phase), and afterward (chronic phase). Individual symptoms and the top 5 and top 11 most severe symptoms were summarized and compared between the radiation therapy modalities.
PRO data were collected and analyzed from 35 patients treated with chemotherapy and IMPT and from 46 treated with chemotherapy and IMRT. The baseline symptom burdens were similar between both groups. The overall top 5 symptoms were food taste problems (mean score 4.91 on a 0-10 scale), dry mouth (4.49), swallowing/chewing difficulties (4.26), lack of appetite (4.08), and fatigue (4.00). Among the top 11 symptoms, changes in taste and appetite during the subacute and chronic phases favored IMPT (all P<.048). No differences in symptom burden were detected between modalities during the acute and chronic phases by top-11 symptom scoring. During the subacute phase, the mean (±standard deviation) top 5 MDASI scores were 5.15 ± 2.66 for IMPT versus 6.58 ± 1.98 for IMRT (P=.013).
According to the MDASI-HN, symptom burden was lower among the IMPT patients than among the IMRT patients during the subacute recovery phase after treatment. A prospective randomized clinical trial is underway to define the value of IMPT for the management of head and neck tumors.
Summary Background Spinal stereotactic body radiation therapy (SBRT) is increasingly used to manage spinal metastases, yet the technique's effectiveness in controlling the symptom burden of spinal ...metastases has not been well described. We investigated the clinical benefit of SBRT for managing spinal metastases and reducing cancer-related symptoms. Methods 149 patients with mechanically stable, non-cord-compressing spinal metastases (166 lesions) were given SBRT in a phase 1–2 study. Patients received a total dose of 27–30 Gy, typically in three fractions. Symptoms were measured before SBRT and at several time points up to 6 months after treatment, by the Brief Pain Inventory (BPI) and the M D Anderson Symptom Inventory (MDASI). The primary endpoint was frequency and duration of complete pain relief. The study is completed and is registered with ClinicalTrials.gov , number NCT00508443. Findings Median follow-up was 15·9 months (IQR 9·5–30·3). The number of patients reporting no pain from bone metastases, as measured by the BPI, increased from 39 of 149 (26%) before SBRT to 55 of 102 (54%) 6 months after SBRT (p<0·0001). BPI-reported pain reduction from baseline to 4 weeks after SBRT was clinically meaningful (mean 3·4 SD 2·9 on the BPI pain-at-its-worst item at baseline, 2·1 2·4 at 4 weeks; effect size 0·47, p=0·00076). These improvements were accompanied by significant reduction in opioid use during the first 6 months after SBRT (43 28·9% of 149 patients with strong opioid use at baseline vs 20 20·0% of 100 at 6 months; p=0·011). Ordinal regression modelling showed that patients reported significant pain reduction according to the MDASI during the first 6 months after SBRT (p=0·00003), and significant reductions in a composite score of the six MDASI symptom interference with daily life items (p=0·0066). Only a few instances of non-neurological grade 3 toxicities occurred: nausea (one event), vomiting (one), diarrhoea (one), fatigue (one), dysphagia (one), neck pain (one), and diaphoresis (one); pain associated with severe tongue oedema and trismus occurred twice; and non-cardiac chest pain was reported three times. No grade 4 toxicities occurred. Progression-free survival after SBRT was 80·5% (95% CI 72·9–86·1) at 1 year and 72·4% (63·1–79·7) at 2 years. Interpretation SBRT is an effective primary or salvage treatment for mechanically stable spinal metastasis. Significant reductions in patient-reported pain and other symptoms were evident 6 months after SBRT, along with satisfactory progression-free survival and no late spinal cord toxicities. Funding National Cancer Institute of the US National Institutes of Health.
Background: Radiation therapy is effective in palliating pain from bone metastases. We investigated whether 8 Gy delivered in a single treatment fraction provides pain and narcotic relief that is ...equivalent to that of the standard treatment course of 30 Gy delivered in 10 treatment fractions over 2 weeks. Methods: A prospective, phase III randomized study of palliative radiation therapy was conducted for patients with breast or prostate cancer who had one to three sites of painful bone metastases and moderate to severe pain. Patients were randomly assigned to 8 Gy in one treatment fraction (8-Gy arm) or to 30 Gy in 10 treatment fractions (30-Gy arm). Pain relief at 3 months after randomization was evaluated with the Brief Pain Inventory. The Wilcoxon–Mann–Whitney test was used to compare response to treatment in terms of pain and narcotic relief between the two arms and for each stratification variable. All statistical comparisons were two-sided. Results: There were 455 patients in the 8-Gy arm and 443 in the 30-Gy arm; pretreatment characteristics were equally balanced between arms. Grade 2–4 acute toxicity was more frequent in the 30-Gy arm (17%) than in the 8-Gy arm (10%) (difference = 7%, 95% CI = 3% to 12%; P = .002). Late toxicity was rare (4%) in both arms. The overall response rate was 66%. Complete and partial response rates were 15% and 50%, respectively, in the 8-Gy arm compared with 18% and 48% in the 30-Gy arm (P = .6). At 3 months, 33% of all patients no longer required narcotic medications. The incidence of subsequent pathologic fracture was 5% for the 8-Gy arm and 4% for the 30-Gy arm. The retreatment rate was statistically significantly higher in the 8-Gy arm (18%) than in the 30-Gy arm (9%) (P<.001). Conclusions: Both regimens were equivalent in terms of pain and narcotic relief at 3 months and were well tolerated with few adverse effects. The 8-Gy arm had a higher rate of re-treatment but had less acute toxicity than the 30-Gy arm.
The Role of Statins in Cancer Therapy Hindler, Katja; Cleeland, Charles S.; Rivera, Edgardo ...
The oncologist (Dayton, Ohio),
March 2006, 2006-Mar, 2006-03-01, 20060301, Letnik:
11, Številka:
3
Journal Article
Recenzirano
Learning Objectives
After completing this course, the reader will be able to:
Explain how statins, used in the treatment of hypercholesterolemia, may be applicable to cancer prevention.
Discuss how ...statins potentially interfere with biologic processes relevant to cancer etiology.
Outline the gaps in our understanding in this area of theoretical versus applied medicine.
Access and take the CME test online and receive 1 AMA PRA category 1 credit at CME.TheOncologist.com
Administration of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors, or statins, to ambulatory patients is associated with a lower incidence of long‐term adverse cardiovascular events, including death, myocardial infarction, stroke, atrial fibrillation, and renal dysfunction. However, increasing clinical evidence suggests that statins, independent of their effects on serum cholesterol levels, may also play a potential role in the prevention and treatment of cancer. Specifically, statins have been shown to exert several beneficial antineo‐plastic properties, including decreased tumor growth, angiogenesis, and metastasis. The feasibility and efficacy of statins for the prevention and treatment of cancer is reviewed.
Cancer and its treatment produce multiple symptoms that significantly distress patients and impair function. Symptoms caused by treatment may delay treatment or lead to premature treatment ...termination, and residual treatment-related symptoms often complicate posttreatment rehabilitation. When treatment is no longer possible, symptom control becomes the focus of cancer care. Patient ratings of symptom severity and impact are important patient-reported outcomes (PROs) in cancer clinical trials and comprise a subset of a larger domain of PROs generally referred to as health-related quality of life (HRQOL). Symptoms rarely occur in isolation; rather, there is now ample evidence that symptoms frequently occur in clusters. The impact of these multiple symptoms upon the patient can be described as “symptom burden,” a concept that encompasses both the severity of the symptoms and the patient's perception of the impact of the symptoms. The distress caused by symptoms is a subject of much investigation, and several validated measures of the severity and impact of multiple symptoms are now available. Symptom measures are generally brief, thereby reducing respondent burden, and can be administered repeatedly during a trial to give a relatively fine-grained picture of the patient's status across time. In many instances, information on trial-related changes in symptom burden, or comparison of symptom burden between arms in a clinical trial, may provide sufficient self-report data for clinical trial consumers (patients, clinicians, and regulators) to make treatment choices or to evaluate new therapies, without measuring other HRQOL domains.
Cancer therapy makes patients sick. The therapies that are available to clinicians allow them to successfully control nausea, emesis and pain. However, this is not the case for a number of other ...symptoms that include fatigue, distractibility, poor memory, and diminished interest in previously pleasurable activities. These symptoms cluster during the course of cancer therapy and impair patient quality of life, limit therapy options and do not always resolve at the cessation of treatment. It is possible to describe the intensity and temporal features of symptoms and assess their relationship with the inflammatory response that is associated with cancer and cancer therapy. At the preclinical level, sophisticated animal models still need to be deployed to study the causal role of inflammation in specific components of cancer-related symptoms. Various approaches can be optimally combined in a translational symptom research pathway to provide a framework for assessing in a systematic manner the neurobehavioral toxicity of existing and newly developed cancer therapies. Ultimately, this knowledge will allow derivation of mechanism-based interventions to prevent or alleviate cancer-related symptoms.
The standard approach for documenting symptomatic adverse events (AEs) in cancer clinical trials involves investigator reporting using the National Cancer Institute's (NCI's) Common Terminology ...Criteria for Adverse Events (CTCAE). Because this approach underdetects symptomatic AEs, the NCI issued two contracts to create a patient-reported outcome (PRO) measurement system as a companion to the CTCAE, called the PRO-CTCAE. This Commentary describes development of the PRO-CTCAE by a group of multidisciplinary investigators and patient representatives and provides an overview of qualitative and quantitative studies of its measurement properties. A systematic evaluation of all 790 AEs listed in the CTCAE identified 78 appropriate for patient self-reporting. For each of these, a PRO-CTCAE plain language term in English and one to three items characterizing the frequency, severity, and/or activity interference of the AE were created, rendering a library of 124 PRO-CTCAE items. These items were refined in a cognitive interviewing study among patients on active cancer treatment with diverse educational, racial, and geographic backgrounds. Favorable measurement properties of the items, including construct validity, reliability, responsiveness, and between-mode equivalence, were determined prospectively in a demographically diverse population of patients receiving treatments for many different tumor types. A software platform was built to administer PRO-CTCAE items to clinical trial participants via the internet or telephone interactive voice response and was refined through usability testing. Work is ongoing to translate the PRO-CTCAE into multiple languages and to determine the optimal approach for integrating the PRO-CTCAE into clinical trial workflow and AE analyses. It is envisioned that the PRO-CTCAE will enhance the precision and patient-centeredness of adverse event reporting in cancer clinical research.
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