Recommendations on the use of item libraries for patient-reported outcome measurement in oncology trials: findings from an international, multidisciplinary working group.

The use of item libraries for patient-reported outcome (PRO) measurement in oncology allows for the customisation of PRO assessment to measure key health-related quality of life concepts of relevance to the target population and intervention. However, no high-level recommendations exist to guide users on the design and implementation of these customised PRO measures (item lists) across different PRO measurement systems. To address this issue, a working group was set up, including international stakeholders (academic, independent, industry, health technology assessment, regulatory, and patient advocacy), with the goal of creating recommendations for the use of item libraries in oncology trials. A scoping review was carried out to identify relevant publications and highlight any gaps. Stakeholders commented on the available guidance for each research question, proposed recommendations on how to address gaps in the literature, and came to an agreement using discussion-based methods. Nine primary research questions were identified that formed the scope and structure of the recommendations on how to select items and implement item lists created from item libraries. These recommendations address methods to drive item selection, plan the structure and analysis of item lists, and facilitate their use in conjunction with other measures. The findings resulted in high-level, instrument-agnostic recommendations on the use of item-library-derived item lists in oncology trials.

Development and validation of a patient-reported outcome measure to assess symptom burden after chimeric antigen receptor T-cell therapy.

This cross-sectional study aimed to develop and validate a patient-reported outcomes (PROs) assessment tool to assess symptom burden and daily functioning in patients after chimeric antigen receptor (CAR) T-cell therapy, the MD Anderson Symptom Inventory (MDASI-CAR). The items were generated based on literature review, content elicitation interviews with patients, and clinician's review. The patients completed the MDASI core and module, single-item quality-of-life (QoL) measure and Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29). The psychometric validation analysis was based on the acceptability after item reduction process. The final 10 MDASI-CAR module items included tremors, fever/chills, headache, balance, dizziness, attention, difficulty speaking, coughing, sexual dysfunction, and diarrhoea with high internal consistency (Cronbach's alpha: MDASI Core, 0.865; MDASI Interference, 0.915; CAR-T module, 0.746). The MDASI-CAR has excellent known-group validity that was demonstrated by differentiate patients based on patient's performance status (Cohen's d for MDASI core = -1.008, interference = -0.771, module = -0.835). Criterion validity was demonstrated by the significant correlations between the MDASI-CAR composite score, the single QoL item and the relevant domains on PROMIS-29 (all p < 0.05). This study established the MDASI-CAR module as a reliable and valid PRO tool for monitoring symptom burden after CAR T-cell therapy in patients with haematological malignancies. The findings need to be validated with a longitudinal design.

Symptom Trajectories Informing Patient Care After Lung Cancer Surgery: A Longitudinal Patient-Reported Outcome Study.

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.

Should We Use COMM (Current Opioid Misuse Measure) to Screen for Opioid Abuse in Patients With Cancer Pain?

BACKGROUND: Growing concerns about opioid use disorder (OUD) and the resulting decrease in opioid availability for patients with cancer pain highlight the need for reliable screening tools to identify the subset of patients at increased risk for aberrant opioid use. Our study examines the utility of Current Opioid Misuse Measure (COMM) recommended by the NCCN Clinical Practice Guidelines in Oncology for Adult Cancer Pain. PATIENTS AND METHODS: We analyzed prospectively collected patient-reported outcomes of 444 consecutive patients with cancer seen in pain clinics of a cancer center at 2 time points within 100 days. The relationship of COMM to other OUD screening tools, pain, opioid doses, patient demographics, and mortality was examined using univariate and multivariable logistic regression. We also examined individual items of COMM for face validity. RESULTS: Among 444 patients who completed pain surveys at 2 time points, 157 (35.4%) did not complete COMM surveys. Using a COMM cutoff of ≥13, a total of 84 patients (29.3%; 84/287) scored positive for aberrant drug use. As patients remained on opioids for 49 to 100 days, the likelihood of improving COMM score (turning from positive to negative) was 6.1 times greater than the reverse. The number of patients with COMM ≥13 was 3.8 times higher than the number of patients with CPT diagnostic codes for OUD, 5.3 times higher than those with a positive urine drug screening, and 21 times higher than those with a positive CAGE (Cut Down, Annoyed, Guilty, Eye-Opener Questionnaire) score. COMM ≥13 was not associated with pain relief response (worst pain intensity score ≥2 points on the Brief Pain Inventory), opioid doses, gender, or age. Contrary to the intended use of COMM to identify aberrant opioid use, COMM ≥13 predicted mortality: patients with COMM ≥13 were 1.9 times more likely to die within 12 months. CONCLUSIONS: Our study found that using COMM in a cancer population may significantly overestimate the risk of opioid misuse. Using COMM without modifications can create an additional barrier to cancer pain management, such as limiting appropriate opioid use.

Patient-reported symptoms at discharge and risk of complications after gynecologic surgery.

OBJECTIVE: Current gaps in knowledge limit clinicians from fully implementing patient-reported outcomes in routine post-operative care. METHODS: This prospective study assessed symptoms via the gynecologic module of the MD Anderson Symptom Inventory (MDASI-PeriOp-GYN) in patients who underwent open laparotomy. RESULTS: At discharge, patient-reported moderate to severe (≥4 on a 0-10 scale) abdominal bloating or abdominal cramping, combined with length of stay of ≥4 days, were found to be associated with a higher risk of 30-day post-operative grade II-IV complications by the Clavien-Dindo system (all p values <0.01). Also, length of stay of ≥4 days and moderate to severe urinary urgency at discharge were found to be associated with the need for re-admission (all p values <0.01). CONCLUSION: This study defined the clinically meaningful symptoms that related to the risk of developing important complications after discharge from major open gynecological surgery.These findings support the integration of assessment of patient-reported outcomes into patient-centered post-operative care.

Development and Validation of a Patient-reported Outcome Measure for Gastrointestinal Obstruction in the Setting of Advanced Malignancy.

OBJECTIVE: We sought to construct a valid and reliable patient-reported outcome measure for patients with advanced malignancy and GIO. BACKGROUND: Bowel obstruction is the most common indication for palliative surgical consultation in patients with advanced cancer; however, no validated patient-reported outcome measures exist for this population. METHODS: A total of 125 patients with GIO and 64 patients without GIO who underwent palliative surgical consultation completed the MDASI-GIO questionnaire and a single global quality-of-life question. Summary statistics were used to assess the symptom burden of GIO patients. Outcome measures were validity (construct and criterion) and reliability (internal and test-retest) for the MDASI-GIO. RESULTS: The majority of patients rated the severity of each of the 5 following GIO-specific symptoms as moderate to severe (rating of ≥5 on a 0 to 10 scale): "being unable to eat'' (72%), "being unable to have a bowel movement'' (65%), "abdominal discomfort'' (62%), "stomach feeling full'' (55%), and "abdominal cramping'' (54%). The MDASI-GIO subscale Cronbach coefficient alpha values were 0.80-0.91, and intraclass correlations were 0.72-0.84. Correlations between MDASI-GIO subscales and global quality of life were -0.39 to-0.49 ( P < 0.001 for all comparisons). GIO patients had significantly worse symptoms and higher interference than did non-GIO patients (all P < 0.05) with effect-size differences of ≥0.36, supporting known-group validity. CONCLUSIONS: The MDASI-GIO shows initial validity and reliability for assessing the severity of symptoms of patients with GIO and the interference of these symptoms in patients' daily functioning.

Establishment of Minimal Clinically Important Improvement for Patient-Reported Symptoms to Define Recovery After Video-Assisted Thoracoscopic Surgery.

PURPOSE: The aim of this study was to define a threshold of minimal clinically important improvement (MCII) for interpreting patient condition following video-assisted thoracoscopic surgery (VATS). METHODS: Patients undergoing VATS were recruited for this multicenter, prospective, observational cohort study. Symptoms were measured using the MD Anderson Symptom Inventory-Lung Cancer Module perioperatively. To define MCIIs, we first identified index symptoms, defined as the most severe symptoms showing the largest reduction from day 1 post-surgery to discharge. MCIIs for each index symptom were then obtained via an anchor-based approach. Symptom recovery was defined as an MCII after post-surgery day 1. Cox regression models were used to identify risk factors for unrecovered index symptoms. RESULTS: Using 366 patients, we identified pain and fatigue as index symptoms after VATS. MCII was defined as a 30% reduction in pain or fatigue. At discharge, 22.6% of patients had not recovered from pain and 22.4% had not recovered from fatigue. Cox models found that risk factors for unrecovered pain were Charlson Comorbidity Index score ≥1 (hazard ratio [HR] 1.36, 95% confidence interval [CI] 1.04-1.77; p = 0.02) and preoperative neoadjuvant therapy (HR 2.78, 95% CI 1.13-6.83; p = 0.02). Malignancy was a risk factor for unrecovered fatigue (HR 1.47, 95% CI 1.02-2.13; p = 0.04). CONCLUSION: Pain and fatigue can be used as index measures for symptom recovery in patients following VATS. A 30% MCII represented meaningful recovery after VATS and could identify patients who may need extensive care after discharge.

Effects of patient-reported outcome assessment order.

BACKGROUND: In clinical trials and clinical practice, patient-reported outcomes are almost always assessed using multiple patient-reported outcome measures at the same time. This raises concerns about whether patient responses are affected by the order in which the patient-reported outcome measures are administered. METHODS: This questionnaire-based study of order effects included adult cancer patients from five cancer centers. Patients were randomly assigned to complete questionnaires via paper booklets, interactive voice response system, or tablet web survey. Linear Analogue Self-Assessment, Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events, and Patient-Reported Outcomes Measurement Information System assessment tools were each used to measure general health, physical function, social function, emotional distress/anxiety, emotional distress/depression, fatigue, sleep, and pain. The order in which the three tools, and domains within tools, were presented to patients was randomized. Rates of missing data, scale scores, and Cronbach's alpha coefficients were compared by the order in which they were assessed. Analyses included Cochran-Armitage trend tests and mixed models adjusted for performance score, age, sex, cancer type, and curative intent. RESULTS: A total of 1830 patients provided baseline patient-reported outcome assessments. There were no significant trends in rates of missing values by whether a scale was assessed earlier or later. The largest order effect for scale scores was due to a large mean score at one assessment time point. The largest difference in Cronbach's alpha between the versions for the Patient-Reported Outcomes Measurement Information System scales was 0.106. CONCLUSION: The well-being of a cancer patient has many different aspects such as pain, fatigue, depression, and anxiety. These are assessed using a variety of surveys often collected at the same time. This study shows that the order in which the different aspects are collected from the patient is not important.

Assessment of physical function by subjective and objective methods in patients undergoing open gynecologic surgery.

OBJECTIVE: To evaluate the utility of patient-reported outcomes (PROs) to measure physical functioning in perioperative care for patients with gynecological (GYN) tumors. METHODS: 180 patients with GYN tumors undergoing open surgery participated in this longitudinal study. The physical functioning was measured by a subjective PRO tool, the Interference subscales of the MD Anderson Symptom Inventory (MDASI-I); as well as by an objective tool, the Timed Up & Go test (TUGT), perioperatively. Longer time (>20 s) needed to complete the TUGT was defined as "Prolonged". Patients completed EuroQoL-5D as well. The association between the scores of MDASI-I items and TUGT was assessed via the Spearman correlation coefficient. The known-group validity was assessed using the t-test and Cohen's D effect size. RESULTS: Compliance rates at preoperative, discharge and postoperative time points of MDASI-I were 98%, 95%, 96%; while TUGT completion rates were 92%, 75%, and 80%, respectively. Patients who had refused TUGT at discharge reported a significantly worse "MDASI-general activity" score compared to patients who completed TUGT (mean score of 7.00 vs. 5.38, P = 0.020). Patient-reported "Walking" on MDASI-I significantly differentiated patients with prolonged vs. those with frail/normal TUGT at discharge (mean score of 4.89 vs. 2.79, Cohen's d effect size = 0.82, P < 0.001). MDASI-I demonstrated excellent known-group validity per performance status and for the EuroQoL-5D subscales. CONCLUSION: Patient-reported physical functioning impairment after GYN surgery correspond with observed worse scores of the objective functioning measure test (TUGT). MDASI-I assessment represents a feasible and valid tool to evaluate functional status and warrants further implementation in the perioperative setting.

Symptom burden and its functional impact in patients with "symptomatic" relapsed or refractory multiple myeloma.

PURPOSE: Relapsed or refractory multiple myeloma (RRMM) is labeled "symptomatic" based on laboratory values, but not relevant to quantitative measure of patient's perspectives. This study aimed to describe symptom burden, health status, and quality of life in RRMM patients. METHODS: The cross-sectional study included 184 MM patients (141 RRMM cases and 43 MM patients on follow-up without diagnosis/treatment of RRMM disease as controls), while 64 RRMM patients also provided longitudinal patient-reported outcomes (PROs) data. Symptomatic status was based on clinical measures of disease activity. PROs included the MD Anderson Symptom Inventory multiple myeloma module (MDASI-MM), single-item quality of life (SIQOL), and EuroQol-5D (EQ-5D). Wilcoxon rank test and effect size were used for comparisons. Regression models were used to describe symptom trajectory and to identify predictors of high symptom burden during 3 months of RRMM therapy. RESULTS: Most patients were clinically identified as symptomatic (93%). RRMM patients tended to report more severe symptoms, with significantly lower QOL scores and more severe fatigue, poor appetite, and lower enjoyment of life compared with controls (all p < 0.05). In RRMM patients, lower hemoglobin and higher B-2 microglobulin levels significantly correlated with higher burdens of fatigue, pain, and muscle weakness and also with lower QOL and EQ-5D scores (all p < 0.05). During RRMM therapy, being female, with any comorbidity, ≥ 65 years old, and ≥ 5 years MM history, contributed to high symptoms burden and poor QOL status (each p < 0.05). CONCLUSIONS: MDASI-MM modules were sensitive to detect the RRMM-related symptoms burden, which correlated with objective clinical measures. RRMM patients reported a more compromised QOL.

Minocycline for symptom reduction in patients with multiple myeloma during maintenance therapy: a phase II placebo-controlled randomized trial.

BACKGROUND: Patients with multiple myeloma (MM) experience substantial cancer/treatment-related symptom burden during maintenance therapy. This is a phase II randomized, double-blinded, placebo-controlled clinical trial to examine the effect of minocycline for symptom reduction by its potential anti-inflammatory effect. METHODS: Eligible MM patients for maintenance therapy were randomized to receive minocycline (100 mg twice daily) or placebo. The MD Anderson Symptom Inventory for MM (MDASI-MM) was used to assess multiple symptoms weekly during the trial. Clinician-rated toxicities and blood samples were prospectively collected. The effect size, area under the curve (AUC), and t tests were used to determine the symptom burden between treatment groups and identify the 5 most-severe MDASI-MM symptoms. The longitudinal analysis compared the changes in symptom severity and associated inflammatory markers between groups over time. RESULTS: Sixty-nine evaluable MM patients (33 from the intervention group and 36 from the placebo group) were included. No grade 3+ adverse events related to study medication were noted. The AUCs for the 5 worst MDASI-MM symptoms (fatigue, pain, disturbed sleep numbness/tingling, and drowsiness) were not significantly different between two arms. Regardless of group assignment, pain reduction was positively associated with decreased serum levels of soluble tumor necrosis factor-α receptors 1 and 2 during therapy (all P < 0.05). CONCLUSIONS: This pPhase II randomized study observed no statistically significant positive signal impact from minocycline on symptom reduction or inflammatory markers during maintenance therapy for MM, although using minocycline was feasible and had a low toxicity profile.

Composite grading algorithm for the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

BACKGROUND: The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events is an item library designed for eliciting patient-reported adverse events in oncology. For each adverse event, up to three individual items are scored for frequency, severity, and interference with daily activities. To align the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events with other standardized tools for adverse event assessment including the Common Terminology Criteria for Adverse Events, an algorithm for mapping individual items for any given adverse event to a single composite numerical grade was developed and tested. METHODS: A five-step process was used: (1) All 179 possible Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events score combinations were presented to 20 clinical investigators to subjectively map combinations to single numerical grades ranging from 0 to 3. (2) Combinations with <75% agreement were presented to investigator committees at a National Clinical Trials Network cooperative group meeting to gain majority consensus via anonymous voting. (3) The resulting algorithm was refined via graphical and tabular approaches to assure directional consistency. (4) Validity, reliability, and sensitivity were assessed in a national study dataset. (5) Accuracy for delineating adverse events between study arms was measured in two Phase III clinical trials (NCT02066181 and NCT01522443). RESULTS: In Step 1, 12/179 score combinations had <75% initial agreement. In Step 2, majority consensus was reached for all combinations. In Step 3, five grades were adjusted to assure directional consistency. In Steps 4 and 5, composite grades performed well and comparably to individual item scores on validity, reliability, sensitivity, and between-arm delineation. CONCLUSION: A composite grading algorithm has been developed and yields single numerical grades for adverse events assessed via the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events, and can be useful in analyses and reporting.

International standards for the analysis of quality-of-life and patient-reported outcome endpoints in cancer randomised controlled trials: recommendations of the SISAQOL Consortium.

Patient-reported outcomes (PROs), such as symptoms, function, and other health-related quality-of-life aspects, are increasingly evaluated in cancer randomised controlled trials (RCTs) to provide information about treatment risks, benefits, and tolerability. However, expert opinion and critical review of the literature showed no consensus on optimal methods of PRO analysis in cancer RCTs, hindering interpretation of results. The Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data Consortium was formed to establish PRO analysis recommendations. Four issues were prioritised: developing a taxonomy of research objectives that can be matched with appropriate statistical methods, identifying appropriate statistical methods for PRO analysis, standardising statistical terminology related to missing data, and determining appropriate ways to manage missing data. This Policy Review presents recommendations for PRO analysis developed through critical literature reviews and a structured collaborative process with diverse international stakeholders, which provides a foundation for endorsement; ongoing developments of these recommendations are also discussed.

Factors affecting symptom presentation in an early-phase clinical trials clinic patient population.

Increasing numbers of oncology therapies are being approved based on early-phase single-arm studies. Yet, little is known regarding the use of patient-reported outcomes in single-arm oncology trials testing novel therapies. We examined patient-reported symptom severity and symptom interference with activity- (WAW: work, general activity, walking) and mood-(REM: relations with others, enjoyment of life, mood) related functioning, and their association with factors known to influence symptom severity reporting, in early-phase clinical trials clinic patients. Patients completed the validated MD Anderson Symptom Inventory, containing 13 severity items and six interference items, each rated on a 0-10 scale (higher scores = worse symptom severity/interference). Performance status (ECOG-PS) and age were ascertained. Multiple linear regression was performed. In 248 phase I patients (51% female, 90% ECOG 0-1, and 74% ≤65 years), 67% of patients had ≥seven concurrent symptoms of any severity level, and 51% of patients described ≥three concurrent symptoms as moderate-to-severe (severity rating ≥ 5). Composite symptom severity, WAW and REM were worse in patients with ECOG-PS ≥ 2 vs. 0-1, and worse in patients with ECOG-PS = 1 than in patients with ECOG-PS = 0. Compared with patients over 65y, adolescent and young adult (AYA) patients (18y-39y) and patients aged 40y to 65y had worse composite symptom severity. As expected, being employed full-time/retired was associated with better symptom profiles in phaseI patients. The variation of symptom burden by performance status and age suggest that these factors need to be considered in the design of early-phase trials, particularly if patient-reported symptoms are used as primary/secondary/exploratory endpoints.

Validation study of the Japanese version of MD Anderson Symptom Inventory for Brain Tumor module.

OBJECTIVE: The MD Anderson Symptom Inventory for Brain Tumor (MDASI-BT) module is a widely used instrument for measuring symptom burden and interference of daily activities in brain tumor patients. This study aims to develop and validate its Japanese version (MDASI-BT-Japanese). METHODS: Following forward and backward translation of the original MDASI-BT into Japanese, understandability and feasibility were assessed by cognitive debriefing. Subsequently, patients with brain tumors were asked to fill out MDASI-BT-Japanese and European Quality of Life-5 Dimensions (EQ-5D). Feasibility, reliability and validity of MDASI-BT-Japanese were assessed. RESULTS: Cognitive debriefing confirmed overall ease of completion and good understandability. The study population composed of 140 patients with brain tumors (most commonly gliomas). The mean symptom severity score and mean interference score were 1.9 ± 1.7 and 2.8 ± 2.7, respectively. The top items included distress and drowsiness for symptom severity and general activity and work for interference. The median time required was 4 minutes (range, 0.5-30), and missing values were seen in 1%. Internal consistency was proven by excellent Cronbach's coefficient alpha (0.94 for symptom severity, 0.92 for interference). Test-retest reliability was assessed with acceptable intra-class correlation coefficient (mean, 0.76). Correlation efficient ranged between 0.7 and 0.9 for convergent validity. Known-group validity was confirmed by significantly different mean symptom severity score and mean interference score among patients with different performance status. As evidence of concurrent validity, MDASI-BT-Japanese correlated with EQ-5D in the hypothesized magnitude and direction. CONCLUSIONS: The newly developed MDASI-BT-Japanese has demonstrated feasibility, reliability and validity in evaluation of clinical benefit in Japanese-speaking brain tumor patients.

Patient-reported outcomes in light of supportive medications in treatment-naïve lung cancer patients.

PURPOSE: The impact of supportive medications on patient-reported outcomes (PROs) has not been systematically evaluated. We describe the supportive medications used by treatment-naïve lung cancer patients and assess their association with PROs from MD Anderson Symptom Inventory (MDASI). METHODS: Treatment-naïve lung cancer patients who completed PROs from MDASI at the initial visit to MD Anderson Cancer Center were included. Medications from the initial visit were abstracted from the electronic medical records system and categorized into therapeutic classes based on U.S. Pharmacopeia v7.0. A chi-square or Mann-Whitney U test was conducted as appropriate. RESULTS: Among 459 patients, ~ 50% took any analgesics and 25% were on opioids. One-third of patients with moderate-severe pain were not on any analgesics. Patients taking opioids had significantly worse median pain scores (6 vs. 0) compared with those not taking any analgesics (p < 0.0001). Higher proportion of patients with moderate-severe pain took opioids compared with those with mild pain (52% vs. 16%, p < 0.0001). Patients on opioids also reported significantly worse scores for five other cancer-specific core symptoms and all six symptoms rating interference with daily life. Only 15% of patients with higher composite score for depression-related symptoms were on antidepressants. However, patients taking antidepressants did not significantly differ in any individual MDASI symptom scores compared with those not on antidepressants (p = 0.4858). CONCLUSIONS: Our results suggest a need for better screening for pain and depression and optimization of pain management in treatment-naïve lung cancer patients since their poor functional status may result in suboptimal cancer therapy.

Minocycline for symptom reduction during radiation therapy for head and neck cancer: a randomized clinical trial.

PURPOSE: Local/systemic symptoms during cancer therapy may be exacerbated by dysregulated inflammation and its downstream toxic effects. Minocycline can suppress proinflammatory cytokine release; therefore, we investigated its potential to reduce patient-reported symptom severity during radiotherapy (RT) for head and neck cancer (HNC). METHODS: Eligible patients for this blinded, placebo-controlled trial were adults with T0-3, N-any, and M0 HNC receiving single-modality RT. Participants were randomized 1:1 to either minocycline (200 mg/day) or placebo during RT. The primary endpoint was the area under the curve (AUC) of 5 prespecified symptoms (pain, fatigue, disturbed sleep, poor appetite, difficulty swallowing/chewing) during RT, assessed with the MD Anderson Symptom Inventory for HNC (MDASI-HN). RESULTS: We analyzed data from 20 evaluable patients per arm. Overall, 75% had oropharyngeal cancer and 78% were male. No grade 3+ adverse events potentially related to study medication were observed. Two minocycline patients required a feeding tube during RT vs 5 placebo patients (P = 0.21). The average daily AUC during RT for the 5 MDASI-HN symptoms was 3.1 (SD = 1.0) for minocycline and 3.7 (SD = 1.7) for placebo (P = 0.16); the 0.37 effect size was less than our 0.70 target. AUC comparisons for several individual symptoms and symptom interference favored minocycline but were not statistically significant. The greatest numerical differences occurred for systemic symptoms, larger toward treatment end, and in early post-RT recovery. CONCLUSIONS: Minocycline was feasible, well tolerated, and achieved a positive signal toward reducing patient-reported symptom severity during RT for HNC, particularly for systemic symptoms. This justifies additional study and informs future trial design.

Interpreting Patient-reported Outcome Scores for Clinical Research and Practice: Definition, Determination, and Application of Cutpoints.

OBJECTIVES: Cutpoints are specific numeric values used to create discrete categories for patient-reported outcome (PRO) items or scales. Cutpoints are widely used in both clinical research and practice. This article offers a definition for cutpoints, describes strategies for determining actionable cutpoints, and discusses considerations related to interpreting cutpoints in clinical applications. METHODS: We clarify the definition of cutpoints for PRO measures and summarize the major statistical approaches for identifying cutpoints, including multivariate analysis of variance and receiver operating characteristic and regression modeling. DISCUSSION: We review issues related to cutpoint determination and interpretation that should be considered when integrating PROs into clinical research and practice, including the selection of anchors, variability of cutpoints, and clinical burden that may be generated when a cutpoint is used as a threshold for further clinical action. KEY POINTS: Cutpoints are widely used to categorize PRO responses in both clinical research and practice. Cutpoints can be derived for PRO measures regardless of the response scale used; however, the mild, moderate, and severe categories generated from numeric cutpoints are distinct from the mild, moderate, and severe categories found in some PRO measures that use verbal descriptors as response options. Bootstrap analysis is recommended to quantify the variability of cutpoints. The application of cutpoints is limited by how well the anchors are chosen and how cutpoints developed using group-level data are applied at the individual level.

Validation and application of a module of the MD Anderson Symptom Inventory for measuring perioperative symptom burden in patients with gynecologic cancer (the MDASI-PeriOp-GYN).

OBJECTIVE: Using patient-reported outcomes (PROs) in perioperative care is increasingly common. We report the development, validation, and application of an MD Anderson Symptom Inventory version for use in patients undergoing surgery for gynecologic cancer or benign conditions (MDASI-PeriOp-GYN). METHODS: Our process included: (1) generating PeriOp-GYN-specific candidate items from qualitative interviews with patients, followed by input from an expert panel; (2) dropping items that lacked independent clinical relevance; (3) validating psychometric properties (reliability, validity) of the resulting MDASI-PeriOp-GYN; and (4) conducting cognitive debriefing interviews with patients to confirm ease of comprehension, relevance, and acceptability. RESULTS: Qualitative interviews with 40 patients generated 9 new PeriOp-GYN symptom items (bloating, abdominal cramping, constipation, hot flashes, dizziness, grogginess/confusion, urinary pain, difficulty urinating, and diarrhea) that, along with the core MDASI items, formed the new MDASI-PeriOp-GYN. A total of 150 patients (minimally invasive surgery (MIS) = 69, open surgery = 81) participated in the validation study; 121 patients also provided retest data. Cronbach alphas were 0.89 for symptoms and 0.86 for interference. Test-retest reliability was 0.88 for all symptom severity items. Known-group validity was supported by the detection of significant differences in symptom and interference levels by performance status (P < 0.01) and for all symptoms by surgery type (P < 0.01). Cognitive debriefing with 20 of the 150 patients demonstrated that the MDASI-PeriOp-GYN is an easy-to-use and understandable tool. CONCLUSIONS: The MDASI-PeriOp-GYN is a valid, reliable, concise tool for measuring symptom severity and functional interference in patients undergoing gynecologic surgery and can be useful in assessing postoperative symptom burden via PROs.

Adult Cancer Pain, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology.

In recent years, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Adult Cancer Pain have undergone substantial revisions focusing on the appropriate and safe prescription of opioid analgesics, optimization of nonopioid analgesics and adjuvant medications, and integration of nonpharmacologic methods of cancer pain management. This selection highlights some of these changes, covering topics on management of adult cancer pain including pharmacologic interventions, nonpharmacologic interventions, and treatment of specific cancer pain syndromes. The complete version of the NCCN Guidelines for Adult Cancer Pain addresses additional aspects of this topic, including pathophysiologic classification of cancer pain syndromes, comprehensive pain assessment, management of pain crisis, ongoing care for cancer pain, pain in cancer survivors, and specialty consultations.