Profiling patient-reported symptom recovery from oesophagectomy for patients with oesophageal squamous cell carcinoma: a real-world longitudinal study.

PURPOSE: Oesophageal squamous cell carcinoma (ESCC) patients have severe symptom burden after oesophagectomy; however, longitudinal studies of symptom recovery after surgery are scarce. This study used longitudinal patient-reported outcome (PRO)-based symptoms to identify severe symptoms and profile symptom recovery from surgery in patients undergoing oesophagectomy. METHODS: Oesophageal cancer patients (N = 327) underwent oesophagectomy were consecutively included between April 2019 and March 2020. Data were extracted from the Sichuan Cancer Hospital's Esophageal Cancer Case Management Registration Database. Symptom assessment time points were pre-surgery and 1, 3, 5, 7, 14, 21, 30, and 90 days post-surgery using the Chinese version of the MD Anderson Symptom Inventory. And each symptom was rated on an 11-point scale, with 0 being 'not present' and 10 being 'as bad as you can imagine'. The symptom recovery trajectories were profiled using mixed effect models and Kaplan-Meier analysis. RESULTS: The most-severe symptoms on day 1 after oesophagectomy were pain, fatigue, dry mouth, disturbed sleep, and distress. The severity of symptoms peaked on day 1 after surgery. The top two symptoms were fatigue (mean: 5.44 [SD 1.88]) and pain (mean: 5.23 [SD 1.29]). Fatigue was more severe 90 days after surgery than at baseline (mean: 1.77 [SD 1.47] vs 0.65 [SD 1.05]; P < .0001). Disturbed sleep and distress persisted from pre-surgery to 90 days post-surgery; average sleep recovery time was up to 20 days, and 50.58% of patients had sleep disturbances 90 days post-surgery. CONCLUSIONS: Early post-operative pain management after oesophagectomy should be considered. Characteristics and intervention strategies of post-operative fatigue, distress, and disturbed sleep in oesophageal cancer patients warrant further studies.

A prospective randomized trial comparing liposomal bupivacaine vs standard bupivacaine wound infiltration in open gynecologic surgery on an enhanced recovery pathway.

BACKGROUND: Value in healthcare is reflected by patient-centered outcomes of care per health dollar expended. Although liposomal bupivacaine is more expensive, it has been shown to provide prolonged analgesia (up to 72 hours). OBJECTIVE: This study aimed to evaluate whether the addition of liposomal bupivacaine to standard bupivacaine could decrease opioid intake and improve pain control after laparotomy for gynecologic surgery compared with standard bupivacaine alone in an enhanced recovery after surgery pathway. STUDY DESIGN: A prospective randomized controlled single-blinded trial of wound infiltration with liposomal bupivacaine plus 0.25% bupivacaine (study arm) vs 0.25% bupivacaine (control arm) was performed at a National Cancer Institute-designated tertiary referral cancer center. Participants were patients aged ≥18 years undergoing exploratory laparotomy for a gynecologic indication. All patients were treated on an enhanced recovery pathway including local wound infiltration before closure. In this study, 266 mg of liposomal bupivacaine (free base; equal to 300 mg bupivacaine HCL)+150 mg of bupivacaine mixed in the same syringe was used in the study arm, and 150 mg of bupivacaine was used in the control arm. The primary outcome was the proportion of patients who were opioid-free within 48 hours after surgery. Secondary outcomes included number of opioid-free days from postoperative day 0 to postoperative day 3, days to first opioid administration, morphine equivalent daily dose, and patient-reported outcomes collected with the MD Anderson Symptom Inventory. The MD Anderson Symptom Inventory was administered as a preoperative baseline, daily while hospitalized, and at least weekly for 8 weeks after discharge. All outcomes were prespecified before data collection. RESULTS: In this study, 102 patients were evaluated. Among them, 16.7% of patients in the study arm received no opioids up to 48 hours compared with 14.8% in the control arm (P=.99). There were no significant differences in the amount of intraoperative opioids administered or days to first opioid use. There was no significant difference between the 2 arms in median cumulative morphine equivalent daily dose (21.3 [study arm] vs 33.8 [control arm]; P=.36) or between the groups in morphine equivalent daily dose per individual day. There were no significant differences in patient-reported pain or interference with walking between the 2 arms or other patient-reported outcomes. CONCLUSION: Within an enhanced recovery after surgery pathway, adding liposomal bupivacaine to 0.25% bupivacaine wound infiltration did not decrease the proportion of patients who were opioid-free within 48 hours after surgery, did not decrease opioid intake, or did not improve patient's self-reported pain and functional recovery compared with standard bupivacaine.

Patient-Reported Outcomes Are Associated With Enhanced Recovery Status in Patients With Bladder Cancer Undergoing Radical Cystectomy.

BACKGROUND: Bladder cancer is a disease of the elderly that is associated with high morbidity in those treated with radical cystectomy. In this observational study of patients with bladder cancer undergoing radical cystectomy, we analyzed and compared patient-reported outcomes from those treated with Enhanced Recovery After Surgery (ERAS) methods versus those who received traditional perioperative care. METHODS: We enrolled patients who underwent radical cystectomy at a high-volume tertiary care referral center from November 2013 to December 2016, when the ERAS concept was being introduced into postoperative care at our institution. Patients reported symptom outcomes using the MD Anderson Symptom Inventory preoperatively and on postoperative days 1 to 5. Mann-Whitney U tests were used to compare symptom burden between the ERAS and traditional-care groups. General linear mixed-effects models were used for longitudinal data; linear regression models were used for multivariable analysis. RESULTS: Patients (N = 383) reported dry mouth, disturbed sleep, drowsiness, fatigue, pain, and lack of appetite as the most severe symptoms. Compared with the traditional-care group, the ERAS group had significantly less pain (est. = -0.98, P = .005), drowsiness (est. = -0.91, P = .009), dry mouth (est. = -1.21, P = .002), disturbed sleep (est. = -0.97, P = .01), and interference with functioning (est. = -0.70, P = .022) (adjusted for age, sex, surgical technique, and neoadjuvant chemotherapy status). CONCLUSIONS: These results suggest that ERAS practice significantly reduced immediate postoperative symptom burden in bladder cancer patients recovering from radical cystectomy, supporting the use of patient-reported symptom burden as an outcome measure in perioperative care.

Perioperative trajectory of patient reported symptoms: a pilot study in gynecologic oncology patients.

OBJECTIVE: With the growing focus on patient-centered care, patient reported outcomes (PROs) are becoming an important component to clinical trials and quality metrics. The objective of this study was to pilot the collection of patient reported symptom burden in women undergoing surgery in a gynecologic oncology practice. METHODS: Perioperative patient reported symptom burden was measured for women undergoing laparotomy on the gynecologic oncology service at the University of Texas MD Anderson Cancer Center. Symptoms were assessed using the M.D. Anderson Symptom Inventory (MDASI-OC), a 27 item tool validated for use in patients with ovarian cancer. The MDASI-OC was administered as a preoperative baseline, daily while admitted to the hospital after surgery, twice a week on the first week after discharge and then weekly until 8 weeks postoperatively. RESULTS: 29 patients were evaluable. Seventy-five percent of patients had a diagnosis of ovarian cancer. Of those patients, half underwent a primary debulking surgery and the other half had neoadjuvant chemotherapy prior to interval cytoreductive surgery. In the postoperative inpatient setting, the five symptoms with the highest overall burden were fatigue, pain, abdominal pain, dry mouth and drowsiness. Longitudinal change of the top 5 symptoms during hospitalization did not show any significant difference between those who had neoadjuvant chemotherapy and those who did not. CONCLUSION: The collection of longitudinal PROs to assess symptom burden is feasible in patients undergoing gynecologic oncology surgery. Patient reported outcomes are a crucial component of patient-centered research and the longitudinal collection and analysis of symptom burden can allow for more meaningful comparisons of surgical technique and perioperative care.

Patient-reported outcomes after oncologic hepatic resection predict the risk of delayed readiness to return to intended oncologic therapy (RIOT).

BACKGROUND: Optimal surgical recovery is critical to readiness to return to intended oncologic therapy (RIOT). The current study defined the value of patient-reported outcomes (PROs) in predicting the risk for delayed RIOT after oncologic hepatic resection. METHODS: In a prospective longitudinal study, perioperative symptoms were assessed using a valid PRO assessment tool, the MD Anderson Symptom Inventory module for hepatectomy perioperative care (MDASI-PeriOp-Hep), for 4 weeks after surgery. The timed up and go test (TUGT) was administered before surgery, by discharge day, and at the first postoperative follow-up visit. Multivariate logistic regression analysis assessed the predictive value of PROs for delayed RIOT. RESULTS: We enrolled 210 patients and analyzed 148 patients who received adjuvant chemotherapy and contributed more than 3 PRO assessments postoperatively. About 36 percent of the patients had delayed RIOT (>5 weeks, range 1-14 weeks). MDASI scores for drowsiness, fatigue, dry mouth, and interference with general activity, walking, and work on day 7 after discharge and MDASI scores for incisional tightness, fatigue, dry mouth, shortness of breath, and interference with work on day 14 after discharge were associated with delayed RIOT (all P < 0.05). Walking and general activity items on the MDASI-Interference subscale on day 7 after discharge were highly correlated with prolonged TUGT scores at discharge (P < 0.01). CONCLUSION: We defined clinically meaningful PROs on MDASI-PeriOp-Hep after hepatic resection that predicted increased risk of delayed RIOT. These findings highlight the importance PROs for monitoring symptoms and functioning 1-2 weeks after discharge to be implementing into perioperative care.

Using group-based trajectory modeling to examine heterogeneity of symptom burden in patients with head and neck cancer undergoing aggressive non-surgical therapy.

PURPOSE: Treatment-related symptom burden varies significantly among patients undergoing radiotherapy or chemoradiotherapy, yet such variation is typically not reflected in the results from single-group studies. We applied group-based trajectory modeling (GBTM) to describe the heterogeneity of symptom burden among patients with head and neck cancer and to identify subgroups with distinct symptom-development trajectories. METHODS: Patients (n = 130) were recruited pretherapy and rated multiple symptoms weekly for 10 weeks via the M. D. Anderson Symptom Inventory. With the mean of five most severe symptoms over time as an outcome measure, GBTM was used to identify patient subgroups with distinct symptom trajectories. Linear mixed-effects modeling (LMM) was applied to compare with GBTM's ability to describe the longitudinal symptom data. RESULTS: The five most severe symptoms were problems with taste, difficulty swallowing or chewing, problems with mucus, fatigue, and dry mouth. A two-group GBTM model identified 68 % of patients as having high symptom burden, associated with older age, worse baseline performance status, and chemoradiotherapy treatment. A four-group GBTM model generated one stable group (4 % of patients) and three groups varying in symptom severity with both linear and quadratic functions over time. LMM revealed symptom-change patterns similar to that produced by GBTM but was inferior in identifying risk factors for high symptom burden. CONCLUSIONS: For cancer patients undergoing aggressive therapy, GBTM is capable of identifying various symptom-burden trajectories and provides severity groupings that will aid research and may be of clinical utility. These results may be generalizable to other cancer types and treatments.

Advantages of Totally Stapled Collard Over Circular Stapled Technique for Cervical Esophagectomy Anastomosis.

BACKGROUND: The quality of life between the totally stapled Collard (TSC) and circular stapled (CS) techniques from the patient's perspective has not been assessed. This longitudinal patient-reported outcome and objective data assessment study aimed to compare the effects of TSC vs CS for cervical anastomosis with minimally invasive esophagectomy (MIE) on the quality of life. METHODS: This single-center, retrospective study included patients with esophageal cancer who underwent MIE and cervical anastomosis between April 2019 and February 2021; of whom, 105 and 216 patients received TSC and CS anastomosis, respectively. The objective metrics were evaluated based on postoperative complications. Patient-reported outcomes instruments using the European Organization for Research and Treatment of Cancer modules were assessed preoperatively. The Quality of Life Questionnaire (QLQ) Core 30 and the QLQ-Oesophagus Module 18 assessed the quality of life. Mixed-effects models examined changes in questionnaire scores. RESULTS: The stenosis rate in the TSC group was significantly lower than that in the CS group. There were no significant differences in other postoperative complications between the groups. In the QLQ Core 30 scale, the TSC group had better emotional function, less fatigue, less appetite loss, and better function than the CS group, with significant differences in different time points between the groups. QLQ-Oesophagus Module 18 revealed that the TSC group had significantly less appetite loss, dysphagia, dry mouth, pain, and obstruction, and better eating and speech than the CS group. CONCLUSIONS: TSC has significant advantages over the CS technique in lowering postoperative symptom burden and improving quality of life for cervical anastomosis on patient-reported outcomes.

Unpleasant symptoms of immunotherapy for people with lung cancer: A mixed-method study.

BACKGROUND: Immunotherapy has changed the outlook for lung cancer treatment. A closer look at the accompanying symptoms from the patient's perspective is necessary to improve their tolerance to the treatment, which is also the basis for standardized symptom management. OBJECTIVE: To describe the symptomatic experiences of patients receiving immunotherapy for lung cancer and explore whether symptoms reported during immunotherapy were associated with survival outcomes. DESIGN: Exploratory sequential mixed-method study. SETTINGS: Patients were continuously recruited from the oncology day ward of Guangdong Provincial People's Hospital between October 2019 and January 2020. PARTICIPANTS: 59 patients with advanced lung cancer and receiving immunotherapy (median [IQR] age was 64 [58-69]; 72.9 % pathological stage was IV) were included in the study. METHODS: A sequential qualitative interview on symptom experiences was conducted from the perspective of lung cancer patients in immunotherapy. Summative content analysis was used to develop a standardized symptom reporting checklist. Survival outcome follow-ups of each patient were conducted 2 years after the interview. RESULTS: 47 symptoms were extracted from the 124 interviews of 59 patients, the common symptoms including musculoskeletal pain (52.5 %), itchy skin (45.8 %), fatigue (45.8 %), cough (44.1 %), shortness of breath (32.2 %), lack of appetite (32.2 %), and rashes (32.2 %). The timing, severity, and interference of symptoms were different among patients. The symptoms of shortness of breath, fatigue and chest pain were more common in chemo-immunotherapy, while dry mouth and blurred vision were more frequent with immunotherapy. The symptoms of musculoskeletal pain, shortness of breath, lack of appetite, drowsiness and taste change were more common for those who died two years after the interviews; for those who survived, the symptoms of rash and chill were more common. CONCLUSIONS: We generated a symptom list related to lung cancer immunotherapy from the patients, provided a closer look at symptoms from the patient's perspective, and suggested differences in the presence of symptoms between the group of treatment and survival outcome. This enables clinicians and nurses to better understand and empathize with the patient's experience, so as to truly practice the essence of patient-centered care, and provide a basis for the development of standardized symptom measurement tools in the future. TWEETABLE ABSTRACT: At least 47 unpleasant symptoms were present in immunotherapy from the perspective of lung cancer patients.

Comparison of Chief Complaints and Patient-Reported Symptoms of Treatment-Naive Lung Cancer Patients Before Surgery.

BACKGROUND: Lung cancer patients without chief complaints have been increasingly identified by physical examination. This study aimed to profile and compare chief complaints with patient-reported symptoms of lung cancer patients before surgery. METHODS: Data were extracted from a multicenter, prospective longitudinal study (CN-PRO-Lung 1) in China from November 2017 to January 2020. A comparison between chief complaints and patient-reported symptoms was analyzed using the Chi-squared test. RESULTS: A total of 201 (50.8%) lung cancer patients without chief complaints were found by physical examination at admission, and 195 (49.2%) patients had chief complaints. The top 5 chief complaints were coughing (38.1%), expectoration (25.5%), chest pain (13.6%), hemoptysis (10.6%), and shortness of breath (5.3%). There were significantly more patients with chief complaints of coughing (38.1% vs 15.0%, P <0.001) and pain (20.5% vs 6.9%, P<0.001) than those with the same symptoms rated ≥4 via MD Anderson Symptom Inventory‒Lung Cancer (MDASI-LC). There were less patients with chief complaints of fatigue (1.8% vs 10.9%, P<0.001), nausea (0.3% vs 2.5%, P=0.006), and vomiting (0.3% vs 1.8%, p=0.032) than those with the same symptoms rated ≥4 via MDASI-LC. In patients without chief complaints, the five most common moderate to severe patient-reported symptoms were disturbed sleep (19.5%), distress (13.5%), dry mouth (13%), sadness (12%), and difficulty remembering (11.1%). CONCLUSION: Symptoms of lung cancer patients not included in the chief complaint could be identified via a patient-reported outcome instrument, suggesting the necessity of implementing the patient-reported outcome assessment before lung cancer surgery for better patient care.

What Do Patients With Non-Small-Cell Lung Cancer Experience? Content Domain for the MD Anderson Symptom Inventory for Lung Cancer.

PURPOSE: Symptom monitoring has demonstrated improved outcomes in patients with cancer, including quality of life, resource utilization, ability to continue treatment, and survival. The use of disease-specific patient-reported outcome (PRO) measures facilitates symptom monitoring. While the MD Anderson Symptom Inventory-Lung Cancer (MDASI-LC), a PRO measure of symptom burden in lung cancer, is psychometrically validated for use in patients with NSCLC, its content validity has not been verified through direct patient input. Our purpose is to describe the symptom experience of patients with NSCLC and to confirm that the MDASI-LC contains the key symptoms specific to NSCLC from the patient perspective. METHODS: Patients with NSCLC described their symptom experience in single qualitative interviews. Content analysis was used to define the content domain for a PRO measure of NSCLC symptom burden. RESULTS: Participants (N = 40) had a mean age of 66.1 years (standard deviation, 10.9 years); 60.0% were male, 77.5% were White, and 56.4% had stage IV disease. Thirty-two symptoms were described, with 6 reported by ≥ 20% of participants. Symptom variations were noted by treatment modality but not by stage of disease. Patients with NSCLC commonly reported shortness of breath, cough, distress, fatigue, pain, and constipation. In patients receiving chemotherapy, treatment-related symptoms, including neuropathy and sore mouth, were commonly noted. The presence of these symptoms resulted in interference with daily activities, relationships, life plans, treatment adherence, and mood. CONCLUSION: The symptoms included in the MDASI-LC are important components of the content domain of an NSCLC symptom burden measure. The presence of these symptoms affect daily life and, therefore, is of clinical consequence.

Intensity Modulated Proton Therapy Versus Intensity Modulated Photon Radiation Therapy for Oropharyngeal Cancer: First Comparative Results of Patient-Reported Outcomes.

PURPOSE: We hypothesized that patients with oropharyngeal cancer treated with intensity modulated proton therapy (IMPT) would have lower symptom burdens, as measured by patient-reported outcome (PRO) surveys, than patients treated with intensity modulated photon therapy (IMRT). METHODS AND MATERIALS: Patients were treated for oropharyngeal cancer from 2006 to 2015 through prospective registries with concurrent chemotherapy and IMPT or chemotherapy and IMRT and completed the MD Anderson Symptom Inventory for Head and Neck Cancer (MDASI-HN) module at various times before treatment (baseline), during treatment (acute phase), within the first 3 months after treatment (subacute phase), and afterward (chronic phase). Individual symptoms and the top 5 and top 11 most severe symptoms were summarized and compared between the radiation therapy modalities. RESULTS: PRO data were collected and analyzed from 35 patients treated with chemotherapy and IMPT and from 46 treated with chemotherapy and IMRT. The baseline symptom burdens were similar between both groups. The overall top 5 symptoms were food taste problems (mean score 4.91 on a 0-10 scale), dry mouth (4.49), swallowing/chewing difficulties (4.26), lack of appetite (4.08), and fatigue (4.00). Among the top 11 symptoms, changes in taste and appetite during the subacute and chronic phases favored IMPT (all P<.048). No differences in symptom burden were detected between modalities during the acute and chronic phases by top-11 symptom scoring. During the subacute phase, the mean (±standard deviation) top 5 MDASI scores were 5.15 ± 2.66 for IMPT versus 6.58 ± 1.98 for IMRT (P=.013). CONCLUSIONS: According to the MDASI-HN, symptom burden was lower among the IMPT patients than among the IMRT patients during the subacute recovery phase after treatment. A prospective randomized clinical trial is underway to define the value of IMPT for the management of head and neck tumors.

Serum interleukin-6 predicts the development of multiple symptoms at nadir of allogeneic hematopoietic stem cell transplantation.

BACKGROUND: During the time of lowest white blood cell count (nadir) of allogeneic hematopoietic stem cell transplantation (allo-HSCT), cancer patients suffer from tremendous symptom burden related to therapy that requires intensive patient care. However, the mechanism underlying the development of multiple symptoms has not been established. METHODS: To explore the role of inflammatory cytokines in the development of treatment-related symptoms, we studied dynamic changes in symptoms and in serum concentrations of inflammatory cytokines (interleukin [IL]-6, IL-8, soluble tumor necrosis factor receptor 1 [sTNF-R1], IL-1 receptor antagonist, and IL-12p40p70) from pretherapy throughout the first 30 days of allo-HSCT in 30 patients with acute myelogenous leukemia or myelodysplastic syndrome. We measured multiple symptoms repeatedly using the M. D. Anderson Symptom Inventory. Mixed-effects modeling was used to analyze longitudinal data. RESULTS: In response to conditioning and stem-cell infusion, serum levels of IL-6 and the severity of multiple symptoms increased rapidly and peaked at nadir. From baseline to nadir (approximately Day 8 post-transplantation), increase in IL-6 was significantly associated with worsening of the most severe symptoms (fatigue, poor appetite, pain, drowsiness, dry mouth, and disturbed sleep; P< .01). During the first 30 days after transplantation, increases in IL-6 (P< .001) and sTNF-R1 (P< .05) significantly predicted the increasing severity of these symptoms. CONCLUSIONS: These results suggest that release of systemic inflammatory cytokines, mainly IL-6, corresponds to an increase in treatment-related multiple-symptom burden during the nadir period of allo-HSCT.