Xin Shelley Wang

Assessing symptom distress in cancer patients: the M.D. Anderson Symptom Inventory.

The purpose of this project was to develop the M. D. Anderson Symptom Inventory (MDASI), a brief measure of the severity and impact of cancer‐related symptoms.

Are the symptoms of cancer and cancer treatment due to a shared biologic mechanism? A cytokine-immunologic model of cancer symptoms

Cancers and cancer treatments produce multiple symptoms that collectively cause a symptom burden for patients. These symptoms include pain, wasting, fatigue, cognitive impairment, anxiety, and depression, many of which co‐occur. There is growing recognition that at least some of these symptoms may share common biologic mechanisms.

A cytokine-based neuroimmunologic mechanism of cancer-related symptoms.

While many of the multiple symptoms that cancer patients have are due to the disease, it is increasingly recognized that pain, fatigue, sleep disturbance, cognitive dysfunction and affective symptoms are treatment related, and may lead to treatment delays or premature treatment termination. This symptom burden, a subjective counterpart of tumor burden, causes significant distress. Progress in understanding the mechanisms that underlie these symptoms may lead to new therapies for symptom control. Recently, some of these symptoms have been related to the actions of certain cytokines that produce a constellation of symptoms and behavioral signs when given exogenously to both humans and animals. The cytokine-induced sickness behavior that occurs in animals after the administration of infectious or inflammatory agents or certain proinflammatory cytokines has much in common with the symptoms experienced by cancer patients. Accordingly, we propose that cancer-related symptom clusters share common cytokine-based neuroimmunologic mechanisms. In this review, we provide evidence from clinical and animal studies that correlate the altered cytokine profile with cancer-related symptoms. We also propose that the expression of coexisting symptoms is linked to the deregulated activity of nuclear factor-kappa B, the transcription factor responsible for the production of cytokines and mediators of the inflammatory responses due to cancer and/or cancer treatment. These concepts open exciting new avenues for translational research in the pathophysiology and treatment of cancer-related symptoms.

The chinese version of the brief pain inventory (BPI-C): its development and use in a study of cancer pain

&NA; We describe the development of a Chinese version of the Brief Pain Inventory (BPI‐C) and demonstrate its reliability and validity. We also report the use of the BPI‐C in a three hospital study of cancer pain and its treatment. As with other language versions of the BPI, factor analysis of the BPI‐C items results in a two factor solution that satisfies the criteria of reproducibility, interpretability and fit in a confirmatory setting. The first factor consists of the four pain severity scales, while the seven pain interference scales comprised the second factor. The BPI‐C proved to be a reliable measure of both the severity and impact of pain in patients with cancer. Coefficient alphas for the pain severity and pain interference items were 0.894 and 0.915, respectively. The sample (N = 147) was gathered at three cancer treatment hospitals in Beijing. The patients from these hospitals reported higher levels of pain severity and pain interference compared with patients in similar studies done at the same time (1991–1992) in the United States and France. This was in keeping with the finding that a larger proportion (67%) of the cancer patients in these Beijing hospitals were judged to have inadequate analgesia as assessed by the Pain Management Index (PMI), an estimate of adherence to the World Health Organization (WHO) guidelines for cancer pain management.

Stereotactic body radiation therapy for management of spinal metastases in patients without spinal cord compression: a phase 1-2 trial

BACKGROUND Spinal stereotactic body radiation therapy (SBRT) is increasingly used to manage spinal metastases, yet the techniques 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.

Fatigue and Sleep Disturbance in Patients with Cancer, Patients with Clinical Depression, and Community-Dwelling Adults

This study compared the severity of fatigue in patients with cancer to the fatigue reported by depressed psychiatric patients and community-dwelling adults. Data were collected for this study during the process of validating a new fatigue assessment tool, the Brief Fatigue Inventory (BFI). The sample included 354 cancer patients, 72 psychiatric patients, and 290 non-patient volunteers. Study subjects reported severity of fatigue and the degree to which fatigue interfered with various aspects of life. Data were also collected on sleep disturbance and demographic variables that might correlate with fatigue. The psychiatric patients reported significantly higher levels of fatigue and fatigue-related interference than the cancer patients, who reported more severe fatigue and interference than the community subjects. The sleep disturbance scores of the cancer patients and the community subjects were significantly correlated with fatigue severity. Although the majority of the psychiatric patients reported sleep disturbance, their sleep disturbance scores were not significantly associated with fatigue severity.

Management of Spinal Metastases From Renal Cell Carcinoma Using Stereotactic Body Radiotherapy

PURPOSE To evaluate the outcomes associated with stereotactic body radiotherapy (SBRT) in the management of spinal metastases from renal cell carcinoma (RCC). METHODS AND MATERIALS SBRT was used in the treatment of patients with spinal metastases from RCC. Patients received either 24 Gy in a single fraction, 27 Gy in three fractions, or 30 Gy delivered in five fractions. Effectiveness of SBRT with respect to tumor control and palliation of pain was assessed using patient-reported outcomes. RESULTS A total of 48 patients with 55 spinal metastases were treated with SBRT with a median follow-up time of 13.1 months (range, 3.3-54.5 months). The actuarial 1-year spine tumor progression free survival was 82.1%. At pretreatment baseline, 23% patients were pain free; at 1 month and 12 months post-SBRT, 44% and 52% patients were pain free, respectively. No Grade 3-4 neurologic toxicity was observed. CONCLUSIONS The data support SBRT as a safe and effective treatment modality that can be used to achieve good tumor control and palliation of pain associated with RCC spinal metastases. Further evaluation with randomized trials comparing SBRT to conventional radiotherapy may be warranted.

Single Nucleotide Polymorphism at rs1982073:T869C of the TGFβ1 Gene Is Associated With the Risk of Radiation Pneumonitis in Patients With Non–Small-Cell Lung Cancer Treated With Definitive Radiotherapy

PURPOSE In search of reliable biologic markers to predict the risk of normal tissue damage by radio(chemo)therapy before treatment, we investigated the association between single nucleotide polymorphisms (SNPs) in the transforming growth factor 1 (TGFbeta1) gene and risk of radiation pneumonitis (RP) in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Using 164 available genomic DNA samples from patients with NSCLC treated with definitive radio(chemo)therapy, we genotyped three SNPs of the TGFbeta1 gene (rs1800469:C-509T, rs1800471:G915C, and rs1982073:T869C) by polymerase chain reaction restriction fragment length polymorphism method. We used Kaplan-Meier cumulative probability to assess the risk of grade > or = 3 RP and Cox proportional hazards analyses to evaluate the effect of TGFbeta1 genotypes on such risk. RESULTS There were 90 men and 74 women in the study, with median age of 63 years. Radiation doses ranging from 60 to 70 Gy (median = 63 Gy) in 30 to 58 fractions were given to 158 patients (96.3%) and platinum-based chemotherapy to 147 (89.6%). Grade > or = 2 and grade > or = 3 RP were observed in 74 (45.1%) and 36 patients (22.0%), respectively. Multivariate analysis found CT/CC genotypes of TGFbeta1 rs1982073:T869C to be associated with a statistically significantly lower risk of RP grades > or = 2 (hazard ratio [HR] = 0.489; 95% CI, 0.227 to 0.861; P = .013) and grades > or = 3 (HR = 0.390; 95% CI, 0.197 to .774; P = 0.007), respectively, compared with the TT genotype, after adjustment for Karnofsky performance status, smoking status, pulmonary function, and dosimetric parameters. CONCLUSION Our results showed that CT/CC genotypes of TGFbeta1 rs1982073:T869C gene were associated with lower risk of RP in patients with NSCLC treated with definitive radio(chemo)therapy and thus may serve as a reliable predictor of RP.

Automated Symptom Alerts Reduce Postoperative Symptom Severity After Cancer Surgery: A Randomized Controlled Clinical Trial

PURPOSE Patients receiving cancer-related thoracotomy are highly symptomatic in the first weeks after surgery. This study examined whether at-home symptom monitoring plus feedback to clinicians about severe symptoms contributes to more effective postoperative symptom control. PATIENTS AND METHODS We enrolled 100 patients receiving thoracotomy for lung cancer or lung metastasis in a two-arm randomized controlled trial; 79 patients completed the study. After hospital discharge, patients rated symptoms twice weekly for 4 weeks via automated telephone calls. For intervention group patients, an e-mail alert was forwarded to the patients clinical team for response if any of a subset of symptoms (pain, disturbed sleep, distress, shortness of breath, or constipation) reached a predetermined severity threshold. No alerts were generated for controls. Group differences in symptom threshold events were examined by generalized estimating equation modeling. RESULTS The intervention group experienced greater reduction in symptom threshold events than did controls (19% v 8%, respectively) and a more rapid decline in symptom threshold events. The difference in average reduction in symptom interference between groups was -0.36 (SE, 0.078; P = .02). Clinicians responded to 84% of e-mail alerts. Both groups reported equally high satisfaction with the automated system and with postoperative symptom control. CONCLUSION Frequent symptom monitoring with alerts to clinicians when symptoms became moderate or severe reduced symptom severity during the 4 weeks after thoracic surgery. Methods of automated symptom monitoring and triage may improve symptom control after major cancer surgery. These results should be confirmed in a larger study.

Validation Study of the Japanese Version of the Brief Fatigue Inventory

Fatigue has been recognized as one of the most distressing symptoms in cancer patients. Concise assessment is essential to managing this symptom. To that end, the Brief Fatigue Inventory (BFI), a 9-item questionnaire, was designed to assess fatigue in cancer patients. The purpose of this study was to examine the validity and reliability of the Japanese version of this scale (BFI-J), when compared with previously validated fatigue instruments. We randomly selected 252 cancer patients and presented them with the BFI-J, along with the Cancer Fatigue Scale; Profile of Mood States fatigue, vigor, and depression subscales; and European Organization for Research and Treatment of Cancer QLQ-C30. Specifically, the reliability and construct, criterion, convergent, and discriminant validity of each instrument were evaluated. Additionally, fatigue severity classification was explored using the BFI-J. The results indicated that the BFI-J is a brief, valid, and feasible measure of fatigue for use with Japanese cancer patients.