Longitudinal perioperative patient-reported outcomes in open compared with minimally invasive hysterectomy.

BACKGROUND: There are few prospective studies in the gynecologic surgical literature that compared patient-reported outcomes between open and minimally invasive hysterectomies within enhanced recovery after surgery pathways. OBJECTIVE: This study aimed to compare prospectively collected perioperative patient-reported symptom burden and interference measures in open compared with minimally invasive hysterectomy cohorts within enhanced recovery after surgery pathways. STUDY DESIGN: We compared patient-reported symptom burden and functional interference in 646 patients who underwent a hysterectomy (254 underwent open surgery and 392 underwent minimally invasive surgery) for benign and malignant indications under enhanced recovery after surgery protocols. Outcomes were prospectively measured using the validated MD Anderson Symptom Inventory, which was administered perioperatively up to 8 weeks after surgery. Cohorts were compared using Fisher exact and chi-squared tests, adjusted longitudinal generalized linear mixed modeling, and Kaplan Meier curves to model return to no or mild symptoms. RESULTS: The open cohort had significantly worse preoperative physical functional interference (P=.001). At the time of hospital discharge postoperatively, the open cohort reported significantly higher mean symptom severity scores and more moderate or severe scores for overall (P<.001) and abdominal pain (P<.001), fatigue (P=.001), lack of appetite (P<.001), bloating (P=.041), and constipation (P<.001) when compared with the minimally invasive cohort. The open cohort also had significantly higher interference in physical functioning (score 5.0 vs 2.7; P<.001) than the minimally invasive cohort at the time of discharge with no differences in affective interference between the 2 groups. In mixed modeling analysis of the first 7 postoperative days, both cohorts reported improved symptom burden and functional interference over time with generally slower recovery in the open cohort. From 1 to 8 postoperative weeks, the open cohort had worse mean scores for all evaluated symptoms and interference measures except for pain with urination, although scores indicated mild symptomatic burden and interference in both cohorts. The time to return to no or mild symptoms was significantly longer in the open cohort for overall pain (14 vs 4 days; P<.001), fatigue (8 vs 4 days; P<.001), disturbed sleep (2 vs 2 days; P<.001), and appetite (1.5 vs 1 days; P<.001) but was significantly longer in the minimally invasive cohort for abdominal pain (42 vs 28 days; P<.001) and bloating (42 vs 8 days; P<.001). The median time to return to no or mild functional interference was longer in the open than in the minimally invasive hysterectomy cohort for physical functioning (36 vs 32 days; P<.001) with no difference in compositive affective functioning (5 vs 5 days; P=.07) between the groups. CONCLUSION: Open hysterectomy was associated with increased symptom burden in the immediate postoperative period and longer time to return to no or mild symptom burden and interference with physical functioning. However, all patient-reported measures improved within days to weeks of both open and minimally invasive surgery and differences were not always clinically significant.

Patient-reported outcome measures in surgical patients with upper gastrointestinal cancers: A qualitative interview study.

BACKGROUND AND OBJECTIVES: Patients with pancreatic and gastroesophageal (PGE) cancers experience high symptom burden, but patient experience throughout multimodality treatment remains unclear. We aimed to delineate the experience and symptom burden of patients throughout their perioperative course. METHODS: Qualitative interviews were performed with 17 surgical patients with PGE cancer. Interview transcripts were analyzed and symptoms were ranked by frequency. An expert panel assessed the relevance of these symptom inventory items. RESULTS: Of the 17 patients included, 35% (n = 6) underwent gastrectomy, 30% (n = 5) underwent esophagectomy, and 35% (n = 6) underwent pancreatectomy; 76% (n = 13) received neoadjuvant systemic chemotherapy and/or chemoradiation. Overall, 32 symptoms were reported, and 19 were reported by over 20% of patients. An expert panel rated nine symptoms to be relevant or very relevant to PGE surgical patients. These symptoms (difficulty swallowing, heartburn/reflux, diarrhea, constipation, flushing/sweating, stomach feeling full, malaise, dizziness, or feeling cold) were added to the core MD Anderson Symptom Inventory (MDASI) if they were commonly reported or reached a threshold relevancy score. CONCLUSIONS: In this qualitative study, we developed a provisional symptom inventory for patients undergoing surgery for PGE cancer. This symptom inventory module of the MDASI for PGE surgical patients will be psychometrically tested for validity and reliability.

Trans-pacific multicenter collaborative study of minimally invasive proximal versus total gastrectomy for proximal gastric and gastroesophageal junction cancers.

BACKGROUND: The current standard operation for proximal gastric and gastroesophageal junction (P/GEJ) cancers with limited esophageal extension is total gastrectomy (TG). TG is associated with impaired appetite and weight loss due to the loss of gastric functions such as production of ghrelin and with anemia due to intrinsic factor loss and vitamin B12 malabsorption. Theoretically, proximal gastrectomy (PG) can mitigate these problems by preserving gastric function. However, PG with direct esophagogastric reconstruction is associated with severe postoperative reflux, delayed gastric emptying, and poor quality of life (QoL). Minimally invasive PG (MIPG) with antireflux techniques has been increasingly performed by experts but is technically demanding owing to its complexity. Moreover, the actual advantages of MIPG over minimally invasive TG (MITG) with regards to postoperative QoL are unknown. Our overall objective of this study is to determine the short-term QoL benefits of MIPG. Our central hypotheses are that MIPG is safe and that patients have improved appetite after MIPG with effective antireflux techniques, which leads to an overall QoL improvement when compared with MITG. METHODS: Enrollment of a total of 60 patients in this prospective survey-collection study is expected. Procedures (MITG versus MIPG, antireflux techniques for MIPG [double-tract reconstruction versus the double-flap technique]) will be chosen based on surgeon and/or patient preference. Randomization is not considered feasible because patients often have strong preferences regarding MITG and MIPG. The primary outcome is appetite level (reported on a 0-10 scale) at 3 months after surgery. With an expected 30 patients per cohort (MITG versus MIPG), this study will have 80% power to detect a one-point difference in appetite level. Patient-reported outcomes will be longitudinally collected (including questions about appetite and reflux), and specific QoL items, body weight, body mass index and ghrelin, albumin, and hemoglobin levels will be compared. DISCUSSION: Surgeons from the US, Japan, and South Korea formed this collaboration with the agreement that the surgical approach to P/GEJ cancers is an internationally important but controversial topic that requires immediate action. At the completion of the proposed research, our expected outcome is the establishment of the benefit and safety of MIPG. TRIAL REGISTRATION: This trial was registered with Clinical Trials Reporting Program Registration under the registration number NCI-2022-00267 on January 11, 2022, as well as with ClinicalTrials.gov under the registration number NCT05205343 on January 11, 2022.

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.

Opioid-sparing anesthesia and patient-reported outcomes after open gynecologic surgery: a historical cohort study.

PURPOSE: Dexmedetomidine and ketamine may be administered intraoperatively as continuous infusions to provide opioid-sparing anesthesia. Recent evidence has yielded controversial results regarding the impact of opioid-free anesthesia on postoperative complications, and there is a gap in knowledge regarding patient-reported outcomes (PROs). This study aimed to determine the impact of opioid-sparing anesthesia and opioid-based anesthesia on PROs among gynecologic patients within an enhanced recovery after surgery (ERAS) program. METHODS: We formed a single-center historical cohort from patients enrolled in another study who underwent open gynecologic surgery on an ERAS program from November 2014 to December 2020 (n = 2,095). We identified two cohorts based on the type of balanced anesthesia administered: 1) opioid-sparing anesthesia defined as the continuous infusion of dexmedetomidine and ketamine (adjuvants) during surgery or 2) opioid-based anesthesia (no adjuvants). We measured the quality of postoperative recovery using the MD Anderson Symptom Inventory (MDASI), a 29-item validated tool that was administered preoperatively, daily while admitted, and weekly after discharge until week 6. The primary outcome was interference with walking. We matched both cohorts and used a multilevel linear mixed-effect model to evaluate the effect of opioid-sparing anesthesia on the primary outcome. RESULTS: In total, 498 patients were eligible (159 in the opioid-sparing anesthesia cohort and 339 in the opioid-based anesthesia cohort), of whom 149 matched pairs were included in the final analysis. Longitudinal assessment showed no significant or clinically important difference in interference with walking (P = 0.99), general activity (P = 0.99), or other PROs between cohorts. Median [interquartile range (IQR)] intraoperative opioid administration (expressed as morphine milligram equivalents [MME]) among matched patients in the opioid-sparing anesthesia cohort was 30 [25-55] mg vs 58 [8-70] mg in the opioid-based anesthesia cohort (P < 0.01). Patients in the opioid-sparing anesthesia cohort had a lower opioid consumption in the postanesthesia care unit than those in the opioid-based anesthesia cohort (MME, 3 [0-10] mg vs 5 [0-15] mg; P < 0.01), but there was no significant difference between cohorts in total postoperative opioid consumption (MME, 23 [0-94] mg vs 35 [13-95] mg P = 0.053). CONCLUSIONS: In this single-center historical cohort study, opioid-sparing anesthesia had no significant or clinically important effects on interference with walking or other PROs in patients undergoing gynecologic surgery compared with opioid-based anesthesia. Opioid-sparing anesthesia was associated with less short-term opioid consumption than opioid-based anesthesia.

RéSUMé: OBJECTIF: La dexmédétomidine et la kétamine peuvent être administrées en peropératoire sous forme de perfusions continues pour fournir une anesthésie avec épargne opioïde. Des données probantes récentes ont présenté des résultats controversés concernant l'impact d'une anesthésie sans opioïdes sur les complications postopératoires, et il existe une lacune dans les connaissances concernant les issues rapportées par les patients (IRP). Cette étude visait à déterminer l'impact d'une anesthésie avec épargne opioïde et d'une anesthésie à base d'opioïdes sur les IRP chez les patientes de chirurgie gynécologique dans le cadre d'un programme de Récupération rapide après la chirurgie (ERAS ­ Enhanced Recovery After Surgery). MéTHODE: Nous avons formé une cohorte historique monocentrique composée de patientes inscrites à une autre étude qui ont bénéficié d'une chirurgie gynécologique avec laparotomie dans le cadre d'un programme d'ERAS entre novembre 2014 et décembre 2020 (n = 2095). Nous avons identifié deux cohortes en fonction du type d'anesthésie équilibrée administrée : 1) anesthésie avec épargne opioïde, définie comme une perfusion continue de dexmédétomidine et de kétamine (adjuvants) pendant la chirurgie, ou 2) anesthésie à base d'opioïdes (sans adjuvants). Nous avons mesuré la qualité de la récupération postopératoire à l'aide de l'inventaire des symptômes MDASI, un outil validé comportant 29 éléments qui a été administré avant l'opération, quotidiennement pendant l'admission et chaque semaine après le congé jusqu'à la semaine 6. Le critère d'évaluation principal était l'interférence avec la marche. Nous avons apparié les deux cohortes et utilisé un modèle linéaire à effets mixtes à plusieurs niveaux pour évaluer l'effet de l'anesthésie avec épargne opioïde sur le critère d'évaluation principal. RéSULTATS: Au total, 498 patientes étaient éligibles (159 dans la cohorte d'anesthésie avec épargne opioïde et 339 dans la cohorte d'anesthésie à base d'opioïdes), dont 149 paires appariées ont été incluses dans l'analyse finale. L'évaluation longitudinale n'a révélé aucune différence significative ou cliniquement importante dans l'interférence avec la marche (P = 0,99), l'activité générale (P = 0,99), ou d'autres IRP entre les deux cohortes. L'administration médiane d'opioïdes peropératoires [écart interquartile (ÉIQ)] (exprimée en équivalents de morphine en milligrammes [EMM]) chez les patientes appariées de la cohorte d'anesthésie avec épargne opioïde était de 30 [25-55] mg vs 58 [8­70] mg dans la cohorte d'anesthésie à base d'opioïdes (P < 0,01). Les patientes de la cohorte d'anesthésie avec épargne opioïde avaient une consommation d'opioïdes plus faible en salle de réveil que celles de la cohorte d'anesthésie à base d'opioïdes (EMM, 3 [0-10] mg vs 5 [0­15] mg; P < 0,01), mais il n'y avait pas de différence significative entre les cohortes dans la consommation totale d'opioïdes postopératoires (EMM, 23 [0-94] mg vs 35 [13­95] mg; P = 0,053). CONCLUSION: Dans cette étude de cohorte historique monocentrique, l'anesthésie avec épargne opioïde n'a eu aucun effet significatif ou cliniquement important sur l'interférence avec la marche ou d'autres IRP chez les patientes bénéficiant d'une chirurgie gynécologique par rapport à l'anesthésie à base d'opioïdes. L'anesthésie avec épargne opioïde était associée à une consommation d'opioïdes moindre à court terme que l'anesthésie à base d'opioïdes.

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.

In Search of the Optimal Outcome Measure for Patients with Advanced Cancer and Gastrointestinal Obstruction: A Qualitative Research Study.

BACKGROUND: Gastrointestinal obstruction (GIO) is the most common indication for palliative surgical consultation in patients with advanced cancer. The purpose of this study is to delineate the symptom burden and experience of these patients. PATIENTS AND METHODS: Twenty patients with advanced cancer and GIO described symptoms at time of surgical consultation. We analyzed the content of interview transcripts and ranked symptoms by frequency and according to an assessment of relevance conducted by an expert panel (surgeons, palliative care physicians, nurses, and patients/caregivers). RESULTS: Among the 20 study patients, malignancy types included colorectal (n = 9), gastric (n = 4), urothelial/renal (n = 3), and other (n = 4), whereas sites of obstruction were the small bowel (n = 11), gastric outlet (n = 3), and large bowel (n = 6). Thirteen patients (65%) had received chemotherapy within 6 weeks. Imaging evidence of a primary/recurrent tumor was documented in 13 patients (65%), carcinomatosis in 11 (55%), and ascites in 16 (80%). Thirty patient symptoms were identified on qualitative interviewing. Seven GIO-specific items were identified as relevant by the expert panel and will be added to the core symptom assessment inventory for further testing. CONCLUSIONS: We identified symptoms of importance that can be used to assess outcome after treatment of patients with advanced cancer and GIO. Testing for validity and reliability will be required before formal survey development.

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.

Tyrosine kinase inhibitor interruptions, discontinuations and switching in patients with chronic-phase chronic myeloid leukemia in routine clinical practice: SIMPLICITY.

SIMPLICITY (NCT01244750) is an observational study exploring tyrosine kinase inhibitor (TKI) use and management patterns in patients with chronic phase-chronic myeloid leukemia in the US and Europe in routine clinical practice. Herein we describe interruptions, discontinuations and switching of TKI therapy during the initial 2 years of treatment among 1121 patients prospectively enrolled between October 1, 2010 and March 7, 2017. Patient characteristics were broadly similar between the imatinib (n = 370), dasatinib (n = 376), and nilotinib (n = 375) cohorts. Treatment interruptions occurred in 16.4% (year 1) and 4.0% (year 2) of patients, mainly attributed to hematologic intolerances. Treatment discontinuations occurred in 21.8% (year 1) and 10.2% (year 2) of patients, with the highest rate within the first 3 months for intolerance. Switching of TKI was seen in 17.8% (year 1) and 9.5% (year 2) of patients. Significant associations were found between TKI switching and female gender (year 1), age ≥65 years at diagnosis (year 2) and treatment with imatinib (year 2). Intolerance was the most common reason given for patients discontinuing and for switching TKI therapy; however resistance was also cited. Lack of response monitoring in routine clinical practice may have resulted in lower identification of resistance in this dataset. Data from SIMPLICITY suggest that, in routine clinical practice, intolerance and resistance to TKIs influence decisions to change treatment. Changes in TKI therapy are frequent, with nearly a third of patients discontinuing their first-line TKI.

What symptoms are important to patients? Developing a symptom burden measure for women with breast cancer.

PURPOSE: The American Cancer Society predicted that 266,120 women would be diagnosed with breast cancer in 2018. Women experience significant symptom burden in response to tumor and treatment-related adverse effects, particularly in advanced disease. Use of valid and reliable patient-reported outcomes (PRO) symptom measures may assist clinicians in systematically monitoring and managing symptoms. The MD Anderson Symptom Inventory (MDASI) is a brief PRO measure of cancer symptom burden; specific symptoms can be added to the core symptoms to produce disease- and treatment-specific modules. The purpose of this study was to describe the patient symptom experience, define the content domain, and generate items for a breast cancer-specific MDASI module for measuring symptom burden in women with breast cancer. METHODS: Women with breast cancer were qualitatively interviewed about their experiences of disease and treatment. Descriptive exploratory analysis identified symptoms and symptom interference to define the symptom burden of breast cancer. An expert panel rated the relevance of the identified symptoms to patients with breast cancer. RESULTS: A conceptual model of breast cancer symptom burden was developed from interviews with 36 women (mean age of 57.9 years, 86.1% had stages I-III, and 52.8% were on chemotherapy and/or radiation therapy) across the breast cancer disease and treatment trajectory. Thirty-six symptoms and 6 interference categories were identified. Symptoms specific to treatment modalities and breast cancer met the criteria for inclusion in the provisional instrument for psychometric testing. CONCLUSIONS: We generated an instrument with content validity for measuring symptom burden specific to women with breast cancer.

Concept domain validation and item generation for the Treatment-Induced Neuropathy Assessment Scale (TNAS).

PURPOSE: Treatment-induced peripheral neuropathy (TIPN) is a difficult problem experienced by patients with cancer that can interfere with their ability to receive optimal therapy. The Treatment-Induced Peripheral Neuropathy Scale (TNAS) is a patient-reported outcome (PRO) measure developed to assess TIPN symptom burden. However, PRO validation is an ongoing process. The aim of this qualitative study was to define the conceptual model, establish content domain validity, and refine items for the TNAS based on patient input. METHODS: Patients who received bortezomib, oxaliplatin, or platinum-taxane combination therapy reported their experience of TIPN in single qualitative audiotaped interviews. Themes of the TIPN experience were identified by descriptive analysis of the transcribed interviews. RESULTS: Three groups of 10 patients each who had received bortezomib, oxaliplatin, or platinum-taxane combination therapy, for a total of 30 patients, reported their experiences. Two themes reported by patients were TIPN sensations and functional interference. Five sensations (numbness, tingling, pain, heat or burning, and coldness) and five functional impacts (using hands, walking, maintaining balance or falling, wearing shoes, and sleeping) were reported by at least 20% of patients and were selected for inclusion in the TNAS v3.0 for additional psychometric testing. CONCLUSIONS: The assessment of TIPN must be convenient, reliable, and practical for patients, who are the most reliable source of information about symptoms. The TNAS, developed with direct patient input, provides an easily administered and conceptually valid method of patient report of TIPN burden for use in research and practice.

Assessment of baseline symptom burden in treatment-naïve patients with lung cancer: an observational study.

BACKGROUND: Patients with newly diagnosed lung cancer who have not yet begun treatment may already be experiencing major symptoms produced by their disease. Understanding the symptomatic effects of cancer treatment requires knowledge of pretreatment symptoms (both severity and interference with daily activities). We assessed pretreatment symptom severity, interference, and quality of life (QOL) in treatment-naïve patients with lung cancer and report factors that correlated with symptom severity. METHODS: This was a retrospective analysis of data collected at initial intake. Symptoms/interference were rated on the MD Anderson Symptom Inventory (MDASI) between 30 days prediagnosis and 45 days postdiagnosis. We examined symptom severity by disease stage and differences in severity by histology. Linear regression analyses identified significant predictors of severe pain and dyspnea. RESULTS: Of 460 eligible patients, 256 (62%) had adenocarcinoma, 30 (7%) had small cell carcinoma, and 100 (24%) had squamous cell carcinoma; > 30% reported moderate-to-severe (rated ≥ 5, 0-10 scale) pretreatment symptoms. The most-severe were fatigue, disturbed sleep, distress, pain, dyspnea, sadness, and drowsiness. Symptoms affected work, enjoyment of life, and general activity (interference) and physical well-being (QOL) the most. Patients with advanced disease (n = 289, 63%) had more-severe symptoms. Cancer stage was associated with pain severity; both histology and cancer stage were associated with severe dyspnea. CONCLUSION: One third of lung cancer patients were symptomatic at initial presentation. Quantification of pretreatment symptom burden can inform patient-specific palliative therapy and differentiate disease-related symptoms from treatment-related toxicities. Poorly controlled symptoms could negatively affect treatment adherence and therapeutic outcomes.

Outcomes of switching to dasatinib after imatinib-related low-grade adverse events in patients with chronic myeloid leukemia in chronic phase: the DASPERSE study.

Chronic, low-grade adverse events are common in patients with chronic myeloid leukemia who are treated with imatinib. These events may decrease patient quality of life and adherence, and may ultimately contribute to a suboptimal response. Alternative, second-generation tyrosine kinase inhibitors, such as dasatinib, are available with the potential to reduce adverse events, improve tolerability, and support long-term treatment goals. We present the final, primary analysis of DASPERSE/CA180-400 (NCT01660906), an open-label, multicenter, phase IV study designed to determine whether chronic, low-grade nonhematologic adverse events in imatinib-treated patients improve after switching to dasatinib, without affecting efficacy. Of the 121 chronic, grade 1/2, imatinib-related adverse events identified at baseline in 39 patients, 77% resolved or improved within 3 months after switching to dasatinib. Dasatinib maintained a consistent safety profile; headache (33%), pleural effusion (26%), fatigue (23%), and rash (23%) were the most common treatment-related adverse events after the switch. Patients either maintained (56%) or improved (44%) their molecular response on dasatinib. Patients who switched to dasatinib also experienced improved patient-reported symptom burden from baseline as assessed by the MD Anderson Symptom Inventory for chronic myeloid leukemia (on a 1-10 scale, mean change in disease-specific score was - 2.24 and core symptom severity score was - 1.06). Overall, the efficacy and quality of life/symptom burden improved in many patients, despite the onset of dasatinib-related adverse events in most patients. This suggests that imatinib-treated patients with chronic, low-grade adverse events could benefit from switching to treatment with dasatinib.

Modification of existing patient-reported outcome measures: qualitative development of the MD Anderson Symptom Inventory for malignant pleural mesothelioma (MDASI-MPM).

PURPOSE: Malignant pleural mesothelioma (MPM) is an aggressive cancer of the lung pleura. The MD Anderson Symptom Inventory (MDASI) is a patient-reported outcome (PRO) measure of symptom burden, the combined impact of disease-related and treatment-related symptoms on functioning. Validated PRO measures may require modification for use in specific study populations. We sought to modify the MDASI for patients with MPM and create a fit-for-purpose symptom-burden measure for use in a clinical trial, according to US Food and Drug Administration guidance on PRO utilization to support labeling claims. METHODS: A literature review for MPM symptoms was conducted. Patients with MPM were qualitatively interviewed about experiences of disease and treatment. Descriptive analysis identified symptoms and interference with functioning to define MPM-related symptom burden. An expert panel rated the relevance of identified symptoms to patients with MPM. Patients who received the investigational drug in a previous Phase I study were interviewed for drug-specific symptoms. RESULTS: Literature review and interviews of 20 patients identified 31 MPM-related symptoms. A conceptual model of MPM-related symptom burden was developed. After expert-panel relevance review, five MPM-specific items and the 13 core MDASI symptoms met criteria for inclusion in a provisional MDASI-MPM for psychometric testing. Interviews with six patients identified six drug-specific symptoms; three were mentioned by multiple patients. Of these three, one was not in the core MDASI. CONCLUSIONS: The MDASI-MPM has established content validity and, with the addition of one symptom item, is ready for psychometric testing as fit-for-purpose for a clinical trial of an investigational agent.

Higher Stem Cell Dose Infusion after Intensive Chemotherapy Does Not Improve Symptom Burden in Older Patients with Multiple Myeloma and Amyloidosis.

Autologous hematopoietic stem cell transplantation (ASCT) for multiple myeloma (MM) is associated with high symptom burden, particularly for older patients and those with amyloid light-chain (AL) amyloidosis. Symptom burden peaks during leukopenia. We hypothesized that higher doses of CD34(+) stem cells would be associated with an improved symptom outcome. Patients undergoing ASCT for MM who were ≥60 years old or had AL amyloidosis were randomized to receive either a standard (4 to 6 × 10(6) cells/kg) or high dose (10 to 15 × 10(6) cells/kg) of CD34(+) cells after melphalan 200 mg/m(2). Symptom burden was assessed via the MD Anderson Symptom Inventory MM module. Eighty patients were enrolled. Median CD34(+) cell doses were 5.1 × 10(6) cells/kg (standard dose) and 10.5 × 10(6) cells/kg (high dose). The most severe symptoms during the first week were fatigue, lack of appetite, drowsiness, disturbed sleep, and pain. The area under the curve for the mean composite severity score of these symptoms was similar between treatment arms (P = .819). Median times to neutrophil, lymphocyte, and platelet engraftment were also similar between groups. IL-6 increased similarly for both groups throughout the ASCT course. Infusion of higher autologous stem cell dose after high-dose chemotherapy does not yield a difference in symptom burden or engraftment time in the first few weeks after ASCT.

Prechemotherapy Touch Sensation Deficits Predict Oxaliplatin-Induced Neuropathy in Patients with Colorectal Cancer.

OBJECTIVE: We examined the emergence of chemotherapy-induced peripheral neuropathy (CIPN), a dose-limiting toxicity of oxaliplatin, over the course of oxaliplatin-based chemotherapy for colorectal cancer (CRC). Predicting which patients will likely develop CIPN is an ongoing clinical challenge. METHODS: Oxaliplatin-naïve patients with CRC underwent quantitative sensory testing (QST) before beginning oxaliplatin-based chemotherapy and then rated CIPN-related symptoms via the MD Anderson Symptom Inventory (MDASI) weekly for 26 weeks. Mixed modeling examined the value of QST for predicting higher CIPN (MDASI numbness/tingling) during treatment. Trajectory analysis identified a patient subgroup with consistently higher CIPN symptoms. RESULTS: Numbness/tingling was the most frequent, most severe symptom, with 51% of patients clustering into a high CIPN subgroup. Touch sensation deficits (Bumps Detection test) significantly predicted the development of more severe numbness/tingling [estimate (est) = 0.106, p = 0.0003]. The high CIPN subgroup reported increased pain (est = 0.472, p < 0.0001) and interference with walking (est = 0.840, p < 0.0001). In the high CIPN subgroup, patient-reported numbness/tingling worsened rapidly in weeks 0-5 (est = 0.57, p < 0.0001) and then more gradually in weeks 6-26 (est = 0.07, p < 0.0001). CONCLUSION: Prechemotherapy screening with a simple, easily administered objective measure of touch sensation deficits (Bumps Detection test) and monitoring of patient-reported numbness/tingling during the first 2-3 chemotherapy cycles may support improved personalized care of CRC patients with oxaliplatin-induced CIPN.

Patient and health care provider perceptions of cancer-related fatigue and pain.

PURPOSE: In 1997, Vogelzang et al. reported that 61 % of patients with cancer indicated fatigue impacted daily life more than pain, and only 37 % of oncologists shared this perception. We provide an update to this study, which can help prioritize symptom assessment and management in the clinic. Study aims were to determine and compare perceptions of patients with cancer and health care providers (HCPs) of the impact of fatigue and pain. METHODS: A random sample of patients with cancer was recruited in the USA by Harris Poll Online and Schlesinger Associates. Oncology HCPs were recruited by Food and Drug Research, Inc. and Toluna, Inc. RESULTS: From June to November 2012, 550 of 1122 eligible patients (49 %), 400 of 533 eligible oncologists (75 %), and 400 of 617 eligible oncology nurses (65 %) completed a survey. Of patients, 58 % reported that fatigue affected their daily lives more than pain while undergoing treatment with chemotherapy versus 29 % of oncologists and 25 % of oncology nurses that had this perception. Ninety-eight percent of patients reported experiencing fatigue, whereas 72 % of oncologists and 84 % of oncology nurses thought this was the case. Eighty-six percent of patients reported pain while undergoing treatment with chemotherapy, whereas 36 % of oncologists and 51 % of oncology nurses believed this occurred. Nausea and vomiting felt by HCPs were the most concerning symptoms for patients (88 %). CONCLUSIONS: This study shows the importance of assessing symptoms by direct patient report during chemotherapy treatment. HCPs continue to underestimate the prevalence and importance of fatigue and pain for patients with cancer, a finding that may alter the management of treatment-related symptoms and may influence the development of patient symptom management plans.

Racial/ethnic disparities in inflammatory gene single-nucleotide polymorphisms as predictors of a high risk for symptom burden in patients with multiple myeloma 1 year after diagnosis.

BACKGROUND: This study was conducted to determine whether any regulatory single-nucleotide polymorphism (SNP) in an inflammatory gene was associated with a high symptom burden in patients 1 year after the diagnosis of multiple myeloma (MM). METHODS: MM patients rated symptoms with the MD Anderson Symptom Inventory multiple myeloma module (MDASI-MM) and provided buccal-swab DNA samples. SNPs for 4 cytokine genes (interleukin 6 [IL6] -174G>C, IL1ß -511C>T, tumor necrosis factor α [TNFα] -308G>A, and IL10 -1082G>A) were tested. Logistic regression models were used to identify SNPs that might predict moderate/severe symptoms (rated ≥ 4 on the MDASI-MM 0-10 scale). For the evaluation of the relationship between SNPs and overall symptom burden, a 2-step cluster analysis was used to divide patients into subgroups with high or low symptom levels. RESULTS: Forty-one percent of the 344 patients enrolled had a high overall symptom burden. The most prevalent moderate/severe symptoms were fatigue (47%), pain (42%), numbness (38%), and bone aches (32%). For non-Hispanic whites, the IL1ß -511 CC genotype was associated with a high overall symptom burden (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.25-4.72; P = .004), whereas the IL6 -174 GG genotype predicted less moderate/severe fatigue (OR, 0.53; 95% CI, 0.29-0.88; P = .013). For other patients, the IL6 -174 GG genotype predicted moderate/severe pain (OR, 3.36; 95% CI, 1.23-13.64; P = .010). CONCLUSIONS: These results support growing evidence showing that inflammation is associated with cancer-related symptoms, and they suggest that racial/ethnic factors contribute to this association.

Measuring the symptom burden associated with the treatment of chronic myeloid leukemia.

We developed a module of the MD Anderson Symptom Inventory (MDASI) for patients with chronic myeloid leukemia (CML). To develop the MDASI-CML, we identified CML-specific symptoms from qualitative interviews with 35 patients. A list of candidate symptoms was reduced by a panel of patients, caregivers, and clinicians to the 13 core MDASI symptom items and 6 CML-specific items; these items were subsequently administered to 30 patients. Cognitive debriefing confirmed that the items were clear, relevant, and easy to use. One additional CML-specific symptom item was added, for a total of 7. The refined MDASI-CML was administered to 152 patients once every 2 weeks for 1 year. The content, concurrent, known-group, and construct validity of the MDASI-CML were evaluated. The internal consistency and test-retest reliabilities of the module were adequate. Longitudinal analysis showed relatively stable symptom severity scores over time. The most severe symptoms were fatigue, drowsiness, disturbed sleep, muscle soreness and cramping, and trouble remembering things. Approximately one-third of the patients who completed the MDASI-CML reported persistent moderate-to-severe symptoms. The MDASI-CML is a valid and reliable symptom assessment instrument that can be used in clinical studies of symptom status in patients with CML.

Inflammatory Breast Cancer: Understanding the Patient Experience.

BACKGROUND: Inflammatory breast cancer (IBC) is an aggressive, locally advanced cancer with a 5-year survival rate of approximately 40%. Although patients with IBC likely experience significant and variable symptom burden from diagnosis through survivorship, the description of the symptom burden in this population is limited. OBJECTIVES: The purpose of this study was to describe the experience of patients with IBC and define the content domain for a patient-reported outcome measure of IBC symptom burden. METHODS: Twenty patients with IBC described their experience in single qualitative interviews. Content analysis was used to define the symptom burden content domain. Relevance ratings by a panel of experts reduced the number of items for a preliminary patient-reported outcome symptom burden measure. RESULTS: The mean (SD) participant age was 52.8 (12.0) years; 50.0% had distant metastatic disease, and 85.0% were currently receiving treatment. Content analysis revealed 45 symptoms, with 20 symptoms reported by greater than or equal to 20% of participants. All participants described localized disease-related symptoms. Treatment-related symptoms varied among participants based on the modalities received. CONCLUSION: Patients with IBC experience symptom burden that is distinct from the symptom burden experienced by patients with non-IBC. IMPLICATIONS FOR PRACTICE: Differentiating the disease-related symptoms of IBC may assist clinicians in making timely and accurate diagnoses for IBC. A disease- and treatment-specific measure of the symptom burden of IBC should be incorporated in clinical practice to allow for regular assessment and evaluation of symptom burden and implementation of evidence-based interventions for symptom management.