ABSTRACT
BACKGROUND: Clinicians regularly prescribe opioids to manage acute and chronic cancer pain, frequently to address acute postoperative pain, and occasionally to manage chronic non-cancer pain. Clinical efficacy may be suboptimal in some patients due to side effects and/or poor response, and opioid rotation/switching (conversions) is frequently necessary. Despite the widespread practice, opioid conversion ratios are inconsistent between clinicians, practices, and countries. Therefore, we performed a scoping systematic review of opioid conversion studies to inform an international eDelphi guideline. METHODS: To ensure a comprehensive review, we conducted a systematic search across multiple databases (OVID Medline, PsycINFO, Embase, EBM-Cochrane Database of Systematic Reviews and Registered Trials, LILACS, IMEMR, AIM, WPRIM) using studies published up to June 2022. Additionally, we performed hand and Google Scholar searches to verify the completeness of our findings. Our inclusion criteria encompassed randomized and non-randomized studies with no age limit, with only a few pediatric studies identified. We included studies on cancer, non-cancer, acute, and chronic pain. The level and grade of evidence were determined based on the Multinational Supportive Care in Cancer (MASCC) criteria. RESULTS: Our search yielded 21,118 abstracts, including 140 randomized (RCT) and 68 non-randomized (NRCT) clinical trials. We compared these results with recently published conversion ratios. Modest correlations were noted between published reviews and the present scoping systematic review. CONCLUSION: The present scoping systematic review found low-quality evidence to support an opioid conversion guideline. We will use these data, including conversion ratios and type and route of administration, to inform an eDelphi guideline.
Subject(s)
Analgesics, Opioid , Cancer Pain , Humans , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/therapeutic use , Cancer Pain/drug therapy , Chronic Pain/drug therapy , Practice Guidelines as Topic , Dose-Response Relationship, Drug , Acute Pain/drug therapyABSTRACT
BACKGROUND: The relationship between CINV duration and recurrence in subsequent cycles is largely unstudied. Our objective was to determine if patients experiencing CINV in their first cycle of chemotherapy (C1) would face increased risk of CINV in later cycles and whether the duration of the CINV would predict increased risk of recurrence. PATIENTS AND METHODS: Using data from a previously reported phase III trial, we assessed patients' recurrence of breakthrough CINV after antiemetic prophylaxis for anthracycline+cyclophosphamide (AC) for breast cancer, comparing C1 short CINV vs. extended CINV as a secondary analysis. Complete response (CR) and CINV duration were primary and secondary endpoints, respectively. CR was considered prophylaxis success; lack of CR was considered treatment failure (TF). RESULTS: Among 402 female patients, 99 (24.6%) had TF in C1 (TF1). The remaining 303 patients (CR1) had ≥93% CR rates in each subsequent cycle, while the 99 patients with TF1 had TF rates of 49.8% for cycles 2-4 (P < .001). The 51 patients with extended TF (≥3 days) in C1 had recurrent TF in 73/105 later cycles (69.5%, P < .001), while the 48 patients with short TF (1-2 days) in C1 had recurrent TF in 33/108 later cycles (30.6%). The relative risk of recurrence after C1 extended TF was 2.28 (CI 1.67-3.11; P < .001) compared to short TF. CONCLUSIONS: Prophylaxis success in C1 led to >90% repeat success across cycles of AC-based chemotherapy. For patients with breakthrough CINV, extended duration strongly predicted recurrent CINV. The duration of CINV should be closely monitored, and augmenting antiemetic prophylaxis considered for future cycles when extended CINV occurs.
Subject(s)
Antiemetics , Antineoplastic Agents , Humans , Female , Vomiting/chemically induced , Vomiting/prevention & control , Vomiting/drug therapy , Nausea/chemically induced , Nausea/prevention & control , Nausea/drug therapy , Cyclophosphamide/adverse effects , Antineoplastic Agents/therapeutic useABSTRACT
BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and dose-limiting side effect of systemic cancer therapy. In many cancer survivors, CIPN persists after treatment ends and is associated with functional impairments, abnormal gait patterns, falls, and diminished quality of life. However, little is known regarding which patients are most likely to develop CIPN symptoms that impair mobility and increase fall risk, when this risk develops, or the optimal timing of early intervention efforts to mitigate the impact of CIPN on functioning and fall risk. This study will address these knowledge gaps by (1) characterizing trajectories of symptoms, functioning, and falls before, during, and after treatment in adults prescribed neurotoxic chemotherapy for cancer; and (2) determining the simplest set of predictors for identifying individuals at risk for CIPN-related functional decline and falls. METHODS: We will enroll 200 participants into a prospective, observational study before initiating chemotherapy and up to 1 year after completing chemotherapy. Eligible participants are aged 40-85 years, diagnosed with stage I-III cancer, and scheduled to receive neurotoxic chemotherapy. We perform objective assessments of vibratory and touch sensation (biothesiometry, tuning fork, monofilament tests), standing and dynamic balance (quiet stance, Timed-Up-and-Go tests), and upper and lower extremity strength (handgrip dynamometry, 5-time repeated chair stand test) in the clinic at baseline, every 4-6 weeks during chemotherapy, and quarterly for 1 year post-chemotherapy. Participants wear devices that passively and continuously measure daily gait quality and physical activity for 1 week after each objective assessment and self-report symptoms (CIPN, insomnia, fatigue, dizziness, pain, cognition, anxiety, and depressive symptoms) and falls via weekly electronic surveys. We will use structural equation modeling, including growth mixture modeling, to examine patterns in trajectories of changes in symptoms, functioning, and falls associated with neurotoxic chemotherapy and then search for distinct risk profiles for CIPN. DISCUSSION: Identifying simple, early predictors of functional decline and fall risk in adults with cancer receiving neurotoxic chemotherapy will help identify individuals who would benefit from early and targeted interventions to prevent CIPN-related falls and disability. TRIAL REGISTRATION: This study was retrospectively registered with ClinicalTrials.gov (NCT05790538) on 3/30/2023.
Subject(s)
Antineoplastic Agents , Neoplasms , Neurotoxicity Syndromes , Peripheral Nervous System Diseases , Adult , Humans , Antineoplastic Agents/adverse effects , Hand Strength , Neoplasms/complications , Observational Studies as Topic , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/diagnosis , Peripheral Nervous System Diseases/drug therapy , Prospective Studies , Quality of Life , Middle Aged , Aged , Aged, 80 and overABSTRACT
PURPOSE: Chemotherapy-induced nausea and vomiting (CINV)'s impact on work loss remains poorly described. We evaluated associations between the duration of CINV episodes, CINV-related work loss (CINV-WL), and CINV-related activity impairment (CINV-AI) in patients with breast cancer receiving highly emetogenic chemotherapy. METHODS: We analyzed data from a prospective CINV prophylaxis trial of netupitant/palonestron and dexamethasone for patients receiving an anthracycline and cyclophosphamide (AC) for breast cancer (NCT0340371). Over the observed CINV duration (0-5 days), we analyzed patient-reported CINV-WL and CINV-AI for the first two chemotherapy cycles. We categorized patients as having either extended (≥ 3 days) or short (1-2 days) CINV duration and quantified its impact on work using the Work Productivity and Activity Impairment Questionnaire (WPAI). RESULTS: Overall, we captured data for 792 cycles in 402 women, including 136 (33.8%) employed patients with 35.3% reporting CINV. Of those with CINV, patients reported CINV-WL in 26 cycles and CINV-AI in 142 cycles. Of those with CINV, 55.3% of extended CINV cycles experienced CINV-WL compared to 16.7% of short CINV cycles (p < 0.001). The relative risk of CINV-WL between extended and short CINV was 3.32 (p < 0.01) for employed patients. The mean difference in CINV-AI scores (higher = worse) between extended and short duration CINV was 5.0 vs. 3.0 (p < 0.001). CONCLUSION: Extended (≥ 3 days) CINV was associated with more than triple the risk of CINV-WL and higher CINV-AI compared with short CINV.
Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/drug therapy , Prospective Studies , Vomiting/chemically induced , Vomiting/prevention & control , Nausea/chemically induced , Nausea/prevention & control , AnthracyclinesABSTRACT
BACKGROUND: The optimal timing of chemoradiotherapy (CRT) for patients with localized gastric cancer remains unclear. This study aimed to compare the survival outcomes between neoadjuvant and postoperative CRT for patients with gastric and gastroesophageal junction (GEJ) cancer. METHODS: This retrospective study analyzed 152 patients with gastric (42%) or GEJ (58%) adenocarcinoma who underwent definitive surgical resection and received either neoadjuvant or postoperative CRT between 2005 and 2017 at the authors' institution. The primary end point of the study was overall survival (OS). RESULTS: The median follow-up period was 37.5 months. Neoadjuvant CRT was performed for 102 patients (67%) and postoperative CRT for 50 patients (33%). The patients who received neoadjuvant CRT were more likely to be male and to have a GEJ tumor, positive lymph nodes, and a higher clinical stage. The median radiotherapy (RT) dose was 50.4 Gy for neoadjuvant RT and 45.0 Gy for postoperative RT (p < 0.001). The neoadjuvant CRT group had a pathologic complete response (pCR) rate of 26% and a greater rate of R0 resection than the postoperative CRT group (95% vs. 76%; p = 0.002). Neoadjuvant versus postoperative CRT was associated with a lower rate of any grade 3+ toxicity (10% vs. 54%; p < 0.001). The multivariable analysis of OS showed lower hazards of death to be independently associated neoadjuvant versus postoperative CRT (hazard ratio [HR] 0.57; 95% confidence interval [CI] 0.36-0.91; p = 0.020) and R0 resection (HR 0.50; 95% CI 0.27-0.90; p = 0.021). CONCLUSIONS: Neoadjuvant CRT was associated with a longer OS, a higher rate of R0 resection, and a lower treatment-related toxicity than postoperative CRT. The findings suggest that neoadjuvant CRT is superior to postoperative CRT in the treatment of gastric and GEJ cancer.
Subject(s)
Esophageal Neoplasms , Stomach Neoplasms , Chemoradiotherapy , Esophageal Neoplasms/therapy , Female , Humans , Male , Neoadjuvant Therapy , Retrospective Studies , Stomach Neoplasms/therapyABSTRACT
BACKGROUND: Studies evaluating antiemetic prophylaxis have primarily focused on the solid tumor setting and single-day regimens. This study evaluates antiemetic prophylaxis and chemotherapy induced nausea and vomiting (CINV) in patients with lymphoma receiving a multiday doxorubicin-cyclophosphamide containing regimen. METHODS: This was a retrospective, single center, cohort study evaluating patients with aggressive non-Hodgkin B-cell lymphoma receiving dose-adjusted R-EPOCH in the hospital. Data was collected from the electronic medical record from April 2016 to September 2019. Complete response over 120 hours was the primary outcome. Secondary outcomes included complete response during the acute and delayed phases as well as complete control. RESULTS: A total of 73 patients who received dose adjusted R-EPOCH were identified. Most patients (n = 39, 53%) were male with a the median age was 63 years (range: 21-81). Most patients received ondansetron 16 mg once daily (n = 48, 66%) on days 1-5 as antiemetic prophylaxis with a minority receiving either dexamethasone (n = 8) or an NK1 antagonist (n = 13) in addition to ondansetron. Complete response rate was 32% and the complete response in the acute and delayed phase was also 32%. CONCLUSION: Control of CINV in patients with lymphoma hospitalized to receive dose-adjusted R-EPOCH was suboptimal, with only 32% of patients achieving complete response. Nearly three-quarters of patients received only a 5HT3 receptor antagonist as scheduled antiemetic therapy without an NK1 receptor antagonist. This data supports the importance of improving awareness of regarding multiday CINV guidelines and ensuring timely update and implementation of these evidence-based guidelines.
Subject(s)
Antiemetics , Antineoplastic Agents , Lymphoma, B-Cell , Antiemetics/therapeutic use , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols , Cohort Studies , Cyclophosphamide/adverse effects , Doxorubicin/adverse effects , Etoposide , Humans , Incidence , Lymphoma, B-Cell/drug therapy , Male , Middle Aged , Nausea/chemically induced , Nausea/drug therapy , Nausea/epidemiology , Prednisone , Retrospective Studies , Rituximab/adverse effects , Vincristine , Vomiting/chemically induced , Vomiting/drug therapy , Vomiting/epidemiologyABSTRACT
BACKGROUND: Patient-reported outcomes (PROs) assessing quality of life (QOL) and symptom burden correlate with clinical outcomes in patients with cancer. However, to the authors' knowledge, data regarding associations between PROs and treatment response are lacking. METHODS: The authors prospectively approached consecutive patients with advanced gastrointestinal cancer who were initiating a new treatment. Prior to treatment, patients reported their QOL (Functional Assessment of Cancer Therapy-General [FACT-G], 4 subscales: Functional, Physical, Emotional, Social; higher scores indicate better QOL) and symptom burden (Edmonton Symptom Assessment System [ESAS], Patient Health Questionnaire-4 [PHQ-4]; higher scores represent greater symptoms). Regression models were used to examine associations of baseline PROs with treatment response (clinical benefit or progressive disease [PD] at time of first scan), healthcare utilization, and survival. RESULTS: From May 2019 to April 2020, a total of 112 patients with advanced gastrointestinal cancer were enrolled. For treatment response, 64.3% had CB and 35.7% had PD. Higher baseline ESAS-Physical (odds ratio, 1.04; P = .027) and lower FACT-G Functional (odds ratio, 0.92; P = .038) scores were associated with PD. Higher ESAS-Physical (hazard ratio [HR], 1.03; P = .044) and lower FACT-G Total (HR, 0.96; P = .005), FACT-G Physical (HR, 0.89; P < .001), and FACT-G Functional (HR, 0.87; P < .001) scores were associated with a greater hospitalization risk. Lower FACT-G Total (HR, 0.96; P = .009) and FACT-G Emotional (HR, 0.86; P = .012) scores as well as higher ESAS-Total (HR, 1.03; P = .014) and ESAS-Physical (HR, 1.04; P = .032) scores were associated with worse survival. CONCLUSIONS: Baseline PROs are associated with treatment response in patients with advanced gastrointestinal cancer, namely physical symptoms and functional QOL, in addition to health care use and survival. The findings of the current study support the association between PROs and important clinical outcomes, including the novel finding of treatment response.
Subject(s)
Gastrointestinal Neoplasms/epidemiology , Patient Reported Outcome Measures , Treatment Outcome , Adult , Aged , Aged, 80 and over , Female , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/therapy , Humans , Male , Middle Aged , Progression-Free Survival , Quality of Life , Surveys and QuestionnairesABSTRACT
BACKGROUND: Weight loss is common in advanced gastric and gastroesophageal junction adenocarcinoma (G/GEA); however, the prognostic implications of weight loss during the first cycle (C1) of chemotherapy remain poorly characterized. In this study, we investigated the impact of early weight loss during systemic treatment as a potential prognostic factor for overall survival (OS) in patients with advanced G/GEA. MATERIALS AND METHODS: We performed a post hoc analysis of three phase III studies of ramucirumab. Patients were categorized into two groups: weight loss of ≥3% and <3% based on weight change during C1 (3-4 weeks) of treatment. OS by weight groups was assessed for each study and as a pooled meta-analysis. The effect of C1 weight change on patient survival was evaluated using univariate and multivariate Cox models. RESULTS: A total of 1,464 patients with weight data at the end of C1 were analyzed: REGARD (n = 311), RAINBOW (n = 591), and RAINFALL (n = 562). For all three studies, there were fewer patients in the weight loss ≥3% than <3% group. OS was numerically shorter for patients with weight loss of ≥3% than for patients with weight loss of <3% during C1 irrespective of treatment arm. Similar treatment independent effects of early weight loss on OS were observed in the meta-analysis. Overall, early weight loss ≥3% was associated with shorter survival in patients receiving active drug as well as placebo/best supportive care. CONCLUSION: This large post hoc analysis demonstrated that weight loss of ≥3% during C1 was a negative prognostic factor for OS in patients with advanced G/GEA. IMPLICATIONS FOR PRACTICE: This comprehensive analysis examining early weight loss during systemic treatment as a predictor of survival outcomes in patients with advanced gastric and gastroesophageal junction adenocarcinoma (G/GEA) includes a large sample size, reliable on-treatment data reported in well-conducted phase III clinical trials, and global representation of cancer patients with advanced G/GEA. Understanding the impact of on-treatment weight loss is clinically relevant and may represent an opportunity for targeted interventions.
Subject(s)
Stomach Neoplasms , Antineoplastic Combined Chemotherapy Protocols , Clinical Trials, Phase III as Topic , Esophagogastric Junction , Humans , Paclitaxel/therapeutic use , Prognosis , Stomach Neoplasms/drug therapy , Weight LossABSTRACT
PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) contributes to avoidable acute care, a metric now tracked in Medicare's oncology outcome measure. CINV is preventable, yet guidelines are often not followed. We sought to quantify acute care involving CINV and other avoidable toxicities after highly emetogenic chemotherapy (HEC) to identify excess risk and assess clinician adherence to antiemesis guidelines for HEC. MATERIALS AND METHODS: We retrospectively evaluated U.S. electronic health records (2012-2018) using Medicare's OP-35 outcome measure to identify avoidable acute care involving any of 10 toxicities, including CINV, after HEC regimens relative to non-HEC. Antiemetic guideline adherence was defined as use ofneurokinin-1 (NKl) receptor antagonists Q5 (RAs) plus 5-hydroxytryptamine type 3 RA+ dexamethasone at HEC initiation. RESULTS: Among 17,609 patients receiving HEC, acute care rates associated with HEC chemotherapy included 32% cisplatin, 31% carboplatin, and 21% anthracycline/cyclosphospharnide (AC), with 76% meeting the criteria as avoidable events. Oxaliplatin rates were 29%. Avoidable acute care occurred 1.83 times (95% confidence interval, 1.76-1.91, p < .0001) as often after HEC versus non-HEC excluding oxaliplatin; CINV-related acute care occurred 2.29 times as often. Nonadherence to antiemesis guidelines occurred in 34% and 24% of cisplatin and AC courses, respectively, because of omission of a NKl RA. CONCLUSIONS: Patients treated with HEC regimens experienced high avoidable acute care use, 1.8 times the risk seen for other chemotherapy. Nonadherence to guideline-directed antiemetic prophylaxis highlights the need to ensure adherence to antiemetic guidelines, including the use of NKl RA in HEC. IMPLICATIONS FOR PRACTICE: After survival, perhaps the most important goal in oncology is limiting avoidable acute care, a goal now used by Medicare to impact cancer reimbursement. This study found that patients treated with highly emetogenic chemotherapy (HEC) regimens had high rates of avoidable acute care use, 1.8 times the risk seen for other chemotherapy. A substantial proportion of the avoidable acute care involved chemotherapy-induced nausea and vomiting. Results showed that incomplete adherence to national antiemetic guidelines for HEC regimens primarily driven by omission of upfront neurokinin-1 receptor antagonist use, suggesting that improved adherence can meaningfully resolve this gap in quality and cost of care.
Subject(s)
Antiemetics , Antineoplastic Agents , Neoplasms , Aged , Antiemetics/therapeutic use , Antineoplastic Agents/adverse effects , Humans , Medicare , Nausea/chemically induced , Nausea/drug therapy , Nausea/prevention & control , Neoplasms/drug therapy , Oxaliplatin/therapeutic use , Retrospective Studies , United States , Vomiting/chemically induced , Vomiting/drug therapy , Vomiting/prevention & controlABSTRACT
BACKGROUND: Survival in patients with metastatic colorectal cancer (mCRC) has been associated with tumor mutational status, muscle loss, and weight loss. We sought to explore the combined effects of these variables on overall survival. MATERIALS AND METHODS: We performed an observational cohort study, prospectively enrolling patients receiving chemotherapy for mCRC. We retrospectively assessed changes in muscle (using computed tomography) and weight, each dichotomized as >5% or ≤5% loss, at 3, 6, and 12 months after diagnosis of mCRC. We used regression models to assess relationships between tumor mutational status, muscle loss, weight loss, and overall survival. Additionally, we evaluated associations between muscle loss, weight loss, and tumor mutational status. RESULTS: We included 226 patients (mean age 59 ± 13 years, 53% male). Tumor mutational status included 44% wild type, 42% RAS-mutant, and 14% BRAF-mutant. Patients with >5% muscle loss at 3 and 12 months experienced worse survival controlling for mutational status and weight (3 months hazard ratio, 2.66; p < .001; 12 months hazard ratio, 2.10; p = .031). We found an association of >5% muscle loss with BRAF-mutational status at 6 and 12 months. Weight loss was not associated with survival nor mutational status. CONCLUSION: Increased muscle loss at 3 and 12 months may identify patients with mCRC at risk for decreased overall survival, independent of tumor mutational status. Specifically, >5% muscle loss identifies patients within each category of tumor mutational status with decreased overall survival in our sample. Our findings suggest that quantifying muscle loss on serial computed tomography scans may refine survival estimates in patients with mCRC. IMPLICATIONS FOR PRACTICE: In this study of 226 patients with metastatic colorectal cancer, it was found that losing >5% skeletal muscle at 3 and 12 months after the diagnosis of metastatic disease was associated with worse overall survival, independent of tumor mutational status and weight loss. Interestingly, results did not show a significant association between weight loss and overall survival. These findings suggest that muscle quantification on serial computed tomography may refine survival estimates in patients with metastatic colorectal cancer beyond mutational status.
Subject(s)
Colorectal Neoplasms , Weight Loss , Aged , Antineoplastic Combined Chemotherapy Protocols , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Female , Humans , Male , Middle Aged , Muscle, Skeletal , Mutation , Proto-Oncogene Proteins B-raf/genetics , Retrospective StudiesABSTRACT
BACKGROUND: Adolescents and young adults (AYAs; aged 15-39 years) with cancer frequently receive intensive measures at the end of life (EoL), but the perspectives of AYAs and their family members on barriers to optimal EoL care are not well understood. METHODS: We conducted qualitative interviews with 28 bereaved caregivers of AYAs with cancer who died in 2013 through 2016 after receiving treatment at 1 of 3 sites (University of Alabama at Birmingham, University of Iowa, or University of California San Diego). Interviews focused on ways that EoL care could have better met the needs of the AYAs. Content analysis was performed to identify relevant themes. RESULTS: Most participating caregivers were White and female, and nearly half had graduated from college. A total of 46% of AYAs were insured by Medicaid or other public insurance; 61% used hospice, 46% used palliative care, and 43% died at home. Caregivers noted 3 main barriers to optimal EoL care: (1) delayed or absent communication about prognosis, which in turn delayed care focused on comfort and quality of life; (2) inadequate emotional support of AYAs and caregivers, many of whom experienced distress and difficulty accepting the poor prognosis; and (3) a lack of home care models that would allow concurrent life-prolonging and palliative therapies, and consequently suboptimal supported goals of AYAs to live as long and as well as possible. Delayed or absent prognosis communication created lingering regret among some family caregivers, who lost the opportunity to support, comfort, and hold meaningful conversations with their loved ones. CONCLUSIONS: Bereaved family caregivers of AYAs with cancer noted a need for timely prognostic communication, emotional support to enhance acceptance of a poor prognosis, and care delivery models that would support both life-prolonging and palliative goals of care. Work to address these challenges offers the potential to improve the quality of EoL care for young people with cancer.
Subject(s)
Caregivers , Hospice Care , Neoplasms , Terminal Care , Adolescent , Adult , Bereavement , Humans , Neoplasms/therapy , Quality of Life , Young AdultABSTRACT
BACKGROUND: Low muscle mass (quantity) is common in patients with advanced cancer, but little is known about muscle radiodensity (quality). We sought to describe the associations of muscle mass and radiodensity with symptom burden, healthcare use, and survival in hospitalized patients with advanced cancer. METHODS: We prospectively enrolled hospitalized patients with advanced cancer from September 2014 through May 2016. Upon admission, patients reported their physical (Edmonton Symptom Assessment System [ESAS]) and psychological (Patient Health Questionnaire-4 [PHQ-4]) symptoms. We used CT scans performed per routine care within 45 days before enrollment to evaluate muscle mass and radiodensity. We used regression models to examine associations of muscle mass and radiodensity with patients' symptom burden, healthcare use (hospital length of stay and readmissions), and survival. RESULTS: Of 1,121 patients enrolled, 677 had evaluable muscle data on CT (mean age, 62.86 ± 12.95 years; 51.1% female). Older age and female sex were associated with lower muscle mass (age: B, -0.16; P<.001; female: B, -6.89; P<.001) and radiodensity (age: B, -0.33; P<.001; female: B, -1.66; P=.014), and higher BMI was associated with higher muscle mass (B, 0.58; P<.001) and lower radiodensity (B, -0.61; P<.001). Higher muscle mass was significantly associated with improved survival (hazard ratio, 0.97; P<.001). Notably, higher muscle radiodensity was significantly associated with lower ESAS-Physical (B, -0.17; P=.016), ESAS-Total (B, -0.29; P=.002), PHQ-4-Depression (B, -0.03; P=.006), and PHQ-4-Anxiety (B, -0.03; P=.008) symptoms, as well as decreased hospital length of stay (B, -0.07; P=.005), risk of readmission or death in 90 days (odds ratio, 0.97; P<.001), and improved survival (hazard ratio, 0.97; P<.001). CONCLUSIONS: Although muscle mass (quantity) only correlated with survival, we found that muscle radiodensity (quality) was associated with patients' symptoms, healthcare use, and survival. These findings underscore the added importance of assessing muscle quality when seeking to address adverse muscle changes in oncology.
Subject(s)
Muscle, Skeletal , Neoplasms , Sarcopenia , Aged , Female , Hospitalization , Humans , Male , Middle Aged , Muscle, Skeletal/diagnostic imaging , Muscle, Skeletal/pathology , Neoplasms/diagnostic imaging , Neoplasms/therapyABSTRACT
Aim: In the absence of comparative studies, guidelines consider neurokinin 1 receptor antagonists (RAs) as interchangeable. We evaluated the pooled efficacy from three cisplatin registration trials, each with arms containing netupitant/palonosetron (NEPA), a fixed neurokinin 1 RA (netupitant)/serotonin Type 3 (5-HT3) RA (palonosetron) combination, and an aprepitant (APR) regimen. Materials & methods: Efficacy data were pooled for rates of complete response (CR: no emesis/no rescue medication), complete protection (CR + no significant nausea), total control (CR + no nausea) and no significant nausea during acute (0-24 h), delayed (>24-120 h) and overall (0-120 h) phases post chemotherapy. Results: Among 621 NEPA and 576 APR patients, response rates were similar for the acute phase, and generally favored NEPA during delayed and overall phases. CR rates for NEPA versus APR were 88.4 versus 89.2%, 81.8 versus 76.9% (p < 0.05) and 78.4 versus 75.0% during the acute, delayed and overall phases, respectively. Conclusion: Oral NEPA administered on day 1 was more effective than a 3-day APR regimen in preventing delayed nausea and vomiting associated with cisplatin.
Lay abstract Oral netupitant/palonosetron (NEPA) is an innovative product that combines two drugs (netupitant and palonosetron) in a single capsule to prevent nausea and vomiting associated with certain types of chemotherapy. In this paper we pooled together the results of three studies comparing the efficacy of NEPA to two drugs from the same classes administered separately (aprepitant regimen) in patients with various solid tumors receiving cisplatin, a type of chemotherapy with a high likelihood of causing nausea and vomiting. In summary, NEPA was more effective than the aprepitant regimen in preventing nausea and vomiting in the later days (days 35) following chemotherapy.
Subject(s)
Antiemetics/administration & dosage , Antineoplastic Agents/adverse effects , Nausea/epidemiology , Neoplasms/drug therapy , Vomiting/epidemiology , Administration, Oral , Adult , Aprepitant/administration & dosage , Cisplatin/adverse effects , Clinical Trials, Phase II as Topic , Clinical Trials, Phase III as Topic , Drug Administration Schedule , Drug Combinations , Female , Humans , Isoquinolines/administration & dosage , Male , Middle Aged , Multicenter Studies as Topic , Nausea/chemically induced , Nausea/prevention & control , Pyridines/administration & dosage , Quinuclidines/administration & dosage , Randomized Controlled Trials as Topic , Vomiting/chemically induced , Vomiting/prevention & controlABSTRACT
BACKGROUND: Selecting study endpoints in prospective cancer cachexia trials remains poorly defined. The aim of this study was to further evaluate associations in changes in weight, body composition, functional outcomes, and patient-reported outcomes (PROs) in patients with metastatic cancer. METHODS: We completed a 2-year (2016-2018) observational study in patients with metastatic solid cancer and ECOG performance status 0 to 2 while receiving chemotherapy and/or immunotherapy. We completed assessments at study enrollment and 3 months from enrollment. We analyzed longitudinal changes in weight and body composition using validated methods. Functional assessments included the 6-Min Walk Test, Timed Up and Go Test, and Short Physical Performance Battery. PROs included the Functional Assessment of Anorexia/Cachexia Therapy and Functional Assessment of Cancer Therapy Fatigue. We analyzed changes in body composition and functional assessment using paired t tests. Additionally, we utilized linear regression models to assess relationships between changes in body composition and function outcomes and PROs, adjusting for age and sex. RESULTS: A total of 57 patients completed baseline assessments, but 19 patients did not complete 3-month assessments (5 died, 1 hospice, 13 withdrew). Of the 38 patients with complete data, the mean age was 61.8 years and 47% were female. Metastatic cancer types included 71% gastrointestinal, 13% lung, and 8% gynecologic. Half received chemotherapy, 16% immunotherapy, and 34% a combination. From enrollment to 3 months, we did not observe a change in weight or skeletal muscle but did find an increase in total adipose tissue (16.9 ± 52.4 cm2, 95% CI - 33.79-0.63; p = 0.059; ~ 1.5 pounds). We did not observe any association with changes in weight with any functional outcomes or PROs. However, greater losses in skeletal muscle were associated with greater declines in physical function (6-Min Walk Test [B = 0.04, p = 0.01], Short Physical Performance Battery [B = 2.44, p < 0.01]). CONCLUSIONS: Patients with metastatic cancer receiving cancer-directed therapy may not experience a change in body weight. However, we found an association between losses in skeletal muscle and greater declines in physical function. Therefore, when selecting study endpoints, prospective cancer cachexia studies may consider selecting changes in body composition over weight.
Subject(s)
Cachexia/etiology , Neoplasms, Second Primary/diagnostic imaging , Neoplasms/complications , Female , Humans , Male , Middle AgedABSTRACT
BACKGROUND: To the authors' knowledge, end-of-life (EOL) care outcomes among adolescents and young adults (AYAs) with cancer who are living in poverty remain poorly understood. The primary aim of the current study was to examine the effect of poverty on EOL care for AYA patients with cancer. METHODS: The authors conducted a multisite, retrospective study of AYA patients with cancer aged 15 to 39 years who died between January 2013 and December 2016 at 3 academic sites. Medical record-based EOL care outcomes included hospice referral, palliative care (PC) consultation, cancer treatment within the last month of life, and location of death. Two measures of poverty were applied: 1) zip code with a median income ≤200% of the federal poverty level; and 2) public insurance or lack of insurance. Logistic regression analyses were conducted. RESULTS: A total of 252 AYA cancer decedents were identified. Approximately 41% lived in a high-poverty zip code and 48% had public insurance or lacked insurance; approximately 70% had at least 1 poverty indicator. Nearly 40% had a hospice referral, 60% had a PC consultation (76% on an inpatient basis), 38% received EOL cancer treatment, and 39% died in the hospital. In bivariable analyses, AYA patients living in low-income zip codes were found to be less likely to enroll in hospice (P ≤ .01), have an early PC referral (P ≤ .01), or receive EOL cancer treatment (P = .03), although only EOL cancer treatment met statistical significance in multivariable models. No differences with regard to location of death (P = .99) were observed. CONCLUSIONS: AYA patients with cancer experience low rates of hospice referral and high rates of in-hospital death regardless of socioeconomic status. Future studies should evaluate early inpatient PC referrals as a possible method for improving EOL care.
Subject(s)
Hospitalization/statistics & numerical data , Neoplasms/therapy , Poverty/statistics & numerical data , Terminal Care/statistics & numerical data , Adolescent , Adult , Female , Hospice Care/methods , Hospice Care/statistics & numerical data , Hospital Mortality , Humans , Male , Palliative Care/methods , Palliative Care/statistics & numerical data , Referral and Consultation/statistics & numerical data , Retrospective Studies , Social Class , Terminal Care/methods , Young AdultABSTRACT
BACKGROUND: NEPA, a combination antiemetic of a neurokinin-1 (NK1 ) receptor antagonist (RA) (netupitant [oral]/fosnetupitant [intravenous; IV]) and 5-HT3 RA, palonosetron] offers 5-day CINV prevention with a single dose. Fosnetupitant solution contains no allergenic excipients, surfactant, emulsifier, or solubility enhancer. A phase III study of patients receiving cisplatin found no infusion-site or anaphylactic reactions related to IV NEPA. However, hypersensitivity reactions and anaphylaxis have been reported with other IV NK1 RAs, particularly fosaprepitant in patients receiving anthracycline-cyclophosphamide (AC)-based chemotherapy. This study evaluated the safety and efficacy of IV NEPA in the AC setting. MATERIALS AND METHODS: This phase IIIb, multinational, randomized, double-blind study enrolled females with breast cancer naive to highly or moderately emetogenic chemotherapy. Patients were randomized to receive a single 30-minute infusion of IV NEPA or single oral NEPA capsule on day 1 prior to AC, in repeated (up to 4) cycles. Oral dexamethasone was given to all patients on day 1 only. RESULTS: A total of 402 patients were included. The adverse event (AE) profiles were similar for IV and oral NEPA and consistent with those expected. Most AEs were mild or moderate with a similarly low incidence of treatment-related AEs in both groups. There were no treatment-related injection-site AEs and no reports of hypersensitivity or anaphylaxis. The efficacy of IV and oral NEPA were similar, with high complete response (no emesis/no rescue) rates observed in cycle 1 (overall [0-120 hours] 73.0% IV NEPA, 77.3% oral NEPA) and maintained over subsequent cycles. CONCLUSION: IV NEPA was highly effective and safe with no associated hypersensitivity and injection-site reactions in patients receiving AC. IMPLICATIONS FOR PRACTICE: As a combination of a neurokinin-1 (NK1 ) receptor antagonist (RA) and 5-HT3 RA, NEPA offers 5-day chemotherapy-induced nausea and vomiting prevention with a single dose and an opportunity to improve adherence to antiemetic guidelines. In this randomized multinational phase IIIb study, intravenous (IV) NEPA (fosnetupitant/palonosetron) was safe and highly effective in patients receiving multiple cycles of anthracycline-cyclophosphamide (AC)-based chemotherapy. Unlike other IV NK1 RAs, the IV NEPA combination solution does not require any surfactant, emulsifier, or solubility enhancer and contains no allergenic excipients. Hypersensitivity reactions and anaphylaxis have been reported with other IV NK1 RAs, most commonly with fosaprepitant in the AC setting. Importantly, there were no injection-site or hypersensitivity reactions associated with IV NEPA.
Subject(s)
Antiemetics , Breast Neoplasms , Anthracyclines/adverse effects , Antibiotics, Antineoplastic/therapeutic use , Antiemetics/adverse effects , Breast Neoplasms/drug therapy , Cyclophosphamide/adverse effects , Female , Humans , Nausea/chemically induced , Nausea/drug therapy , Nausea/prevention & control , Quinuclidines/therapeutic use , Vomiting/chemically induced , Vomiting/drug therapyABSTRACT
BACKGROUND: Metastatic esophagogastric cancers (EGCs) have a poor prognosis with an approximately 5% 5-year survival. Additional treatment approaches are needed. c-MET gene-amplified tumors are an uncommon but potentially targetable subset of EGC. Clinical characteristics and outcomes were evaluated in patients with MET-amplified EGC and compared with those without MET amplification to facilitate identification of these patients and possible treatment approaches. PATIENTS AND METHODS: Patients with locally advanced or metastatic MET-amplified EGC at Massachusetts General Hospital (MGH) were identified using fluorescent in situ hybridization analysis, with a gene-to-control ratio of ≥2.2 defined as positive. Non-MET-amplified patients identified during the same time period who had undergone tumor genotyping and treatment at MGH were evaluated as a comparison group. RESULTS: We identified 233 patients evaluated for MET amplification from 2002 to 2019. MET amplification was seen in 28 (12%) patients versus 205 (88%) patients without amplification. Most MET-amplified tumors occurred in either the distal esophagus (n = 9; 32%) or gastroesophageal junction (n = 10; 36%). Of MET-amplified patients, 16 (57%) had a TP53 mutation, 5(18%) had HER2 co-amplification, 2 (7.0%) had EGFR co-amplification, and 1 (3.5%) had FGFR2 co-amplification. MET-amplified tumors more frequently had poorly differentiated histology (19/28, 68.0% vs. 66/205, 32%; p = .02). Progression-free survival to initial treatment was substantially shorter for all MET-amplified patients (5.6 vs. 8.8 months, p = .026) and for those with metastatic disease at presentation (4.0 vs. 7.6 months, p = .01). Overall, patients with MET amplification had shorter overall survival (19.3 vs. 24.6 months, p = .049). No difference in survival was seen between low MET-amplified tumors (≥2.2 and <25 MET copy number) compared with highly amplified tumors (≥25 MET copy number). CONCLUSION: MET-amplified EGC represents a distinct clinical entity characterized by rapid progression and short survival. Ideally, the identification of these patients will provide opportunities to participate in clinical trials in an attempt to improve outcomes. IMPLICATIONS FOR PRACTICE: This article describes 233 patients who received MET amplification testing and reports (a) a positivity rate of 12%, similar to the rate of HER2 positivity in this data set; (b) the clinical characteristics of poorly differentiated tumors and nodal metastases; and (c) markedly shorter progression-free survival and overall survival in MET-amplified tumors. Favorable outcomes are reported for patients treated with MET inhibitors. Given the lack of published data in MET-amplified esophagogastric cancers and the urgent clinical importance of identifying patients with MET amplification for MET-directed therapy, this large series is a valuable addition to the literature and will have an impact on future practice.
Subject(s)
Esophageal Neoplasms , Gene Amplification , Stomach Neoplasms , Adult , Aged , Esophageal Neoplasms/genetics , Esophageal Neoplasms/therapy , Esophagogastric Junction , Female , Humans , In Situ Hybridization, Fluorescence , Male , Massachusetts , Middle Aged , Prognosis , Proto-Oncogene Proteins c-met , Stomach Neoplasms/genetics , Stomach Neoplasms/therapy , Treatment OutcomeABSTRACT
BACKGROUND: Clinician adherence to antiemetic guidelines for preventing chemotherapy-induced nausea and vomiting (CINV) caused by highly emetogenic chemotherapy (HEC) remains poorly characterized. The primary aim of this study was to evaluate individual clinician adherence to HEC antiemetic guidelines. PATIENTS AND METHODS: A retrospective analysis of patients receiving HEC was conducted using the IBM Watson Explorys Electronic Health Record Database (2012-2018). HEC antiemetic guideline adherence was defined as prescription of triple prophylaxis (neurokinin-1 receptor antagonist [NK1 RA], serotonin type-3 receptor antagonist, dexamethasone) at initiation of cisplatin or anthracycline + cyclophosphamide (AC). Clinicians who prescribed ≥5 HEC courses were included and individual guideline adherence was assessed, noting the number of prescribing clinicians with >90% adherence. RESULTS: A total of 217 clinicians were identified who prescribed 2,543 cisplatin and 1,490 AC courses. Patients (N=4,033) were primarily women (63.3%) and chemotherapy-naïve (92%) with a mean age of 58.6 years. Breast (36%) and thoracic (19%) cancers were the most common tumor types. Guideline adherence rates of >90% were achieved by 35% and 58% of clinicians using cisplatin or AC, respectively. Omission of an NK1 RA was the most common practice of nonadherence. Variation in prophylaxis guideline adherence was considerable for cisplatin (mean, 71%; SD, 29%; coefficient of variation [CV], 0.40) and AC (mean, 84%; SD, 26%; CV, 0.31). CONCLUSIONS: Findings showed substantial gaps in clinician adherence to HEC CINV guidelines, including a high variability across clinicians. Clinicians should review their individual clinical practices and ensure adherence to evidence-based CINV guidelines to optimize patient care.
Subject(s)
Antiemetics/therapeutic use , Guideline Adherence/standards , Nausea/drug therapy , Vomiting/drug therapy , Antiemetics/pharmacology , Female , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
Breakthrough chemotherapy-induced nausea and vomiting (CINV) is nausea and/or vomiting occurring within 5 days of chemotherapy administration despite using guideline-directed prophylactic antiemetic agents. It is highly prevalent (30-40%), usually requiring immediate treatment or "rescue" medication. If breakthrough CINV occurs, antiemetic guidelines recommend using an antiemetic agent from a different class not used in prophylaxis, along with intravenous hydration and/or dexamethasone. Data supporting these guideline recommendations are limited. Importantly, costs associated with breakthrough CINV can be substantial (i.e., unscheduled hydrations). Two retrospective analyses evaluating guideline-adherent CINV prophylaxis suggest that the initial antiemetic selection may decrease breakthrough CINV. Here we review optimal CINV prophylactic strategies and introduce unscheduled hydration as a potential important surrogate for breakthrough CINV aligning with cost-effective cancer care.
Subject(s)
Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Fluid Therapy , Nausea/etiology , Nausea/therapy , Vomiting/etiology , Vomiting/therapy , Antiemetics/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Clinical Decision-Making , Clinical Trials, Phase III as Topic , Disease Management , Humans , Nausea/prevention & control , Treatment Outcome , Vomiting/prevention & controlABSTRACT
PURPOSE: Opioid-induced constipation (OIC) is a distressing physical symptom for patients with cancer taking opioids. Total opioid consumption may contribute to developing worsening OIC-related symptoms. We completed a retrospective analysis examining the association of total daily opioid consumption on self-reported constipation in patients with cancer. METHODS: In over 5 clinic visits, we collected self-reported constipation scores and 24-h oral morphine equivalents (OME). We examined the association between OME and the presence of constipation (i.e., score > 3) and the relationship of OME between patients with or without constipation. RESULTS: Of 297 patients with cancer, we observed 57.8% with constipation and 42.4% without constipation at the first clinic visit. Age was similar in both groups (54.2 ± 14.5 vs. 56.4 ± 14.8 years [mean ± SD]) and the majority of patients were women (63.7% vs. 61.1%). The most common cancer type in patients with constipation was non-colorectal gastrointestinal (n = 25, 14.6%), while in patients without constipation was colorectal gastrointestinal (n = 25; 19.8%). Across visits, we observed weak or no association between OME and self-reported constipation (r = 0.01-0.27). At the first visit, higher mean OME was seen in patients who self-reported constipation (133.4 vs 76; p < 0.05). Age, sex, metastatic disease, and stimulant laxative use were not associated with constipation. CONCLUSIONS: We observed weak to no association between OME and constipation in patients with cancer. These results suggest a lack of a clear association between total opioid consumption and self-reported constipation.