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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., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The quality of palliative and end-of-life (EOL) care for adolescents and young adults (AYAs) with cancer remains largely unknown. Objective: To describe caregivers of AYA cancer decedents perspectives' on EOL care quality related to EOL care communication. Design: Cross-sectional observational study. Setting/Subjects: Caregivers (n = 35) of AYAs who died from a cancer diagnosis from 2013-2016 were recruited from 3 U.S. academic medical centers. Measurements: Caregiver participants completed structured surveys (FAMCARE scale and the Toolkit After-Death Bereaved Family Member Interview) by telephone to gather perceptions of quality of EOL care of their AYA cancer decedents. Results: Caregivers reported unmet needs regarding preparation for the time of death (50%), the dying process (45%) and unmet spiritual/ religious needs (38%). Lowest quality of EOL care scores related to communication and emotional support. Conclusions: Our findings call for special focus on providing information about what to expect during the dying process and adequately addressing spiritual and religious preferences during EOL care for AYAs.

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., (© 2021. Society of Surgical Oncology.)

Chemotherapy-induced nausea and vomiting (CINV) is a common adverse event associated with many anticancer therapies and can negatively impact patients' quality of life and potentially limit the effectiveness of chemotherapy. Currently, CINV can be prevented in most patients with guideline-recommended antiemetic regimens. However, clinicians do not always follow guidelines, and patients often face difficulties adhering to their prescribed treatments. Therefore, approaches to increase guideline adherence need to be implemented. NEPA is the first and only fixed combination antiemetic, composed of netupitant (oral)/fosnetupitant (intravenous) and palonosetron, which, together with dexamethasone, constitute a triple antiemetic combination recommended for the prevention of CINV for patients receiving highly emetogenic chemotherapy and for certain patients receiving moderately emetogenic chemotherapy. Thus, NEPA offers a convenient and straightforward antiemetic treatment that could improve adherence to guidelines. This review provides an overview of CINV, evaluates the accumulated evidence of NEPA's antiemetic activity and safety from clinical trials and real-world practice, and examines the preliminary evidence of antiemetic control with NEPA in daily clinical settings beyond those described in pivotal trials. Moreover, we review the utility of NEPA in controlling nausea and preserving patients' quality of life during chemotherapy, two major concerns in managing patients with cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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.

Purpose: We performed a NCI-sponsored, prospective study of neoadjuvant FOLFIRINOX followed by chemoradiation with carboplatin/paclitaxel followed by surgery in patients with locally advanced gastric or gastroesophageal cancer., Patients and Methods: The primary objective was to determine completion rate of neoadjuvant FOLFIRINOX × 8 followed by chemoradiation. Secondary endpoints were toxicity and pathologic complete response (pCR) rate. Exploratory analysis was performed of circulating tumor DNA (ctDNA) to treatment response., Results: From October 2017 to June 2018, 25 patients were enrolled. All patients started FOLFIRINOX, 92% completed all eight planned cycles, and 88% completed chemoradiation. Twenty (80%) patients underwent surgical resection, and 7 had a pCR (35% in resected cohort, 28% intention to treat). Tumor-specific mutations were identified in 21 (84%) patients, of whom 4 and 17 patients had undetectable and detectable ctDNA at baseline, respectively. Presence of detectable post-chemoradiation ctDNA ( P = 0.004) and/or postoperative ctDNA ( P = 0.045) were associated with disease recurrence., Conclusions: Here we show neoadjuvant FOLFIRINOX followed by chemoradiation for locally advanced gastroesophageal cancer is feasible and yields a high rate of pCR. ctDNA appears to be a promising predictor of postoperative recurrence. See related commentary by Catenacci, p. 6281 ., (©2021 American Association for Cancer Research.)

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.

This paper presents an overview of the efficacy of intravenous (IV) NEPA (fixed combination of the NK 1 RA, fosnetupitant, and 5-HT 3 RA, palonosetron) relative to oral NEPA and also to historical data for other NK 1 RA regimens. Data is compiled from 5 pivotal NEPA studies in adult chemotherapy-naïve patients with solid tumors undergoing either cisplatin- or anthracycline cyclophosphamide (AC)-based chemotherapy. Additionally, data was reviewed from 10 pivotal Phase 3 studies utilizing other NK 1 RA regimens approved for clinical use. The overall (0-120 h) complete response (no emesis, no rescue use), no emesis, and no significant nausea rates for IV NEPA were similar to that of oral NEPA and were consistently numerically higher than historical NK 1 RA regimens. As a single-dose prophylactic antiemetic combination given with dexamethasone, IV NEPA is a highly effective and convenient guideline-compliant antiemetic agent which may offer a safety benefit over other IV NK 1 RA regimens due to its lack of associated hypersensitivity and injection-site reactions., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: ctDNA offers a promising, noninvasive approach to monitor therapeutic efficacy in real-time. We explored whether the quantitative percent change in ctDNA early after therapy initiation can predict treatment response and progression-free survival (PFS) in patients with metastatic gastrointestinal cancer., Experimental Design: A total of 138 patients with metastatic gastrointestinal cancers and tumor profiling by next-generation sequencing had serial blood draws pretreatment and at scheduled intervals during therapy. ctDNA was assessed using individualized droplet digital PCR measuring the mutant allele fraction in plasma of mutations identified in tumor biopsies. ctDNA changes were correlated with tumor markers and radiographic response., Results: A total of 138 patients enrolled. A total of 101 patients were evaluable for ctDNA and 68 for tumor markers at 4 weeks. Percent change of ctDNA by 4 weeks predicted partial response (PR, P < 0.0001) and clinical benefit [CB: PR and stable disease (SD), P < 0.0001]. ctDNA decreased by 98% (median) and >30% for all PR patients. ctDNA change at 8 weeks, but not 2 weeks, also predicted CB ( P < 0.0001). Four-week change in tumor markers also predicted response ( P = 0.0026) and CB ( P = 0.022). However, at a clinically relevant specificity threshold of 90%, 4-week ctDNA change more effectively predicted CB versus tumor markers, with a sensitivity of 60% versus 24%, respectively ( P = 0.0109). Patients whose 4-week ctDNA decreased beyond this threshold (≥30% decrease) had a median PFS of 175 days versus 59.5 days (HR, 3.29; 95% CI, 1.55-7.00; P < 0.0001)., Conclusions: Serial ctDNA monitoring may provide early indication of response to systemic therapy in patients with metastatic gastrointestinal cancer prior to radiographic assessments and may outperform standard tumor markers, warranting further evaluation., (©2020 American Association for Cancer Research.)

Background: NEPA, a combination antiemetic of a neurokinin-1 (NK 1 ) receptor antagonist (RA) (netupitant [oral]/fosnetupitant [intravenous; IV]) and 5-HT 3 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 NK 1 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 (NK 1 ) receptor antagonist (RA) and 5-HT 3 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 NK 1 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 NK 1 RAs, most commonly with fosaprepitant in the AC setting. Importantly, there were no injection-site or hypersensitivity reactions associated with IV NEPA., (© 2019 The Authors. The Oncologist published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

During cancer therapy, tumor heterogeneity can drive the evolution of multiple tumor subclones harboring unique resistance mechanisms in an individual patient 1-3 . Previous case reports and small case series have suggested that liquid biopsy (specifically, cell-free DNA (cfDNA)) may better capture the heterogeneity of acquired resistance 4-8 . However, the effectiveness of cfDNA versus standard single-lesion tumor biopsies has not been directly compared in larger-scale prospective cohorts of patients following progression on targeted therapy. Here, in a prospective cohort of 42 patients with molecularly defined gastrointestinal cancers and acquired resistance to targeted therapy, direct comparison of postprogression cfDNA versus tumor biopsy revealed that cfDNA more frequently identified clinically relevant resistance alterations and multiple resistance mechanisms, detecting resistance alterations not found in the matched tumor biopsy in 78% of cases. Whole-exome sequencing of serial cfDNA, tumor biopsies and rapid autopsy specimens elucidated substantial geographic and evolutionary differences across lesions. Our data suggest that acquired resistance is frequently characterized by profound tumor heterogeneity, and that the emergence of multiple resistance alterations in an individual patient may represent the 'rule' rather than the 'exception'. These findings have profound therapeutic implications and highlight the potential advantages of cfDNA over tissue biopsy in the setting of acquired resistance.

Background: Effective leadership is necessary to meet the complex care needs of patients with serious, life-limiting illness. The Cambia Health Foundation Sojourns Scholars Program is advancing leadership in palliative care through supporting emerging leaders. The 2016 Cohort has implemented a range of projects to promote their leadership development. Objective: To describe the leadership themes emerging from individual project implementation of the 2016 Sojourns Leadership. Methods: We summarize the synthesized leadership themes derived from both remote and in-person meetings and written reflections of the 2016 Cambia Sojourn Leadership Cohort. Results: The 2016 Cambia Sojourn Leadership Scholar Cohort projects are described. We identified three leadership themes related to palliative care initiatives: openness and flexibility, partnership and team building, and leveraging expertise and risk. Discussion: Unprecedented challenges in a rapidly changing health environment demand palliative care leadership to influence care quality, delivery, policy, and clinical care. Flexibility and openness; partnership and team building; and expertise to implement change emerged as critical themes to advancing the care of patients with serious, life-limiting illness. These leadership themes are consistent with both previous Cambia Sojourns Scholar cohorts and the literature, are essential for the next generation of leaders to implement new models of quality palliative care, payment for palliative care, and education for patients, caregivers, and health care providers. Conclusion: In order to design and implement quality palliative care, leadership development is essential. Use of flexibility and openness; partnership and team building; and expertise to implement change are important themes for success. Whether through the Cambia Health Foundation Sojourns Leadership Program or opportunities within professional organizations, cultivation of the next generation of leaders is critical.

Background: NEPA, an oral fixed combination of the NK1RA netupitant (300 mg) and clinically/pharmacologically distinct 5-HT3RA palonosetron (PALO, 0.50 mg), is the first fixed antiemetic combination to have been approved. A single oral NEPA capsule plus dexamethasone (DEX) given before anthracycline-cyclophosphamide (AC) and non-AC highly emetogenic chemotherapy (HEC) showed superior prevention of chemotherapy-induced nausea and vomiting (CINV) over PALO plus DEX for 5 days postchemotherapy. The safety of NEPA was well-established in the phase II/III clinical program in 1169 NEPA-treated patients. An intravenous (i.v.) formulation of the NEPA combination (fosnetupitant 235 mg plus PALO 0.25 mg) has been developed., Patients and Methods: This randomized, multinational, double-blind, stratified (by sex and country) phase III study (NCT02517021) in chemotherapy-naïve patients with solid tumors assessed the safety of a single dose of i.v. NEPA infused over 30 min before initial and repeated cycles of HEC. Patients received either i.v. NEPA or oral NEPA, both with oral DEX on days 1-4. Safety was assessed primarily by treatment-emergent adverse events (AEs) and electrocardiograms., Results: A total of 404 patients completed 1312 cycles. The incidence and type of treatment-emergent AEs were similar for both treatment groups with the majority of AEs as mild/moderate in intensity. There was no increased incidence of AEs in subsequent cycles in either group. The incidence of treatment-related AEs was similar and relatively low in both groups (12.8% i.v. NEPA and 11.4% oral NEPA during the entire study), with constipation being the most common (6.4% i.v. NEPA, 6.0% oral NEPA). No serious treatment-related AEs occurred in either group. No infusion site or anaphylactic reactions related to i.v. NEPA occurred. No clinically relevant changes in QTc and no cardiac safety concerns were observed., Conclusions: Intravenous NEPA was well-tolerated with a similar safety profile to oral NEPA in patients with various solid tumors receiving HEC.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Antiemesis address all aspects of management for chemotherapy-induced nausea and vomiting. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Antiemesis, specifically those regarding carboplatin, granisetron, and olanzapine., (Copyright © 2017 by the National Comprehensive Cancer Network.)

Background: Despite the availability of effective antiemetics and evidence-based guidelines, up to 40% of cancer patients receiving chemotherapy fail to achieve complete nausea and vomiting control. In addition to type of chemotherapy, several patient-related risk factors for chemotherapy-induced nausea and vomiting (CINV) have been identified. To incorporate these factors into the optimal selection of prophylactic antiemetics, a repeated measures cycle-based model to predict the risk of ≥ grade 2 CINV (≥2 vomiting episodes or a decrease in oral intake due to nausea) from days 0 to 5 post-chemotherapy was developed., Patients and Methods: Data from 1198 patients enrolled in one of the five non-interventional CINV prospective studies were pooled. Generalized estimating equations were used in a backwards elimination process with the P-value set at <0.05 to identify the relevant predictive factors. A risk scoring algorithm (range 0-32) was then derived from the final model coefficients. Finally, a receiver-operating characteristic curve (ROCC) analysis was done to measure the predictive accuracy of the scoring algorithm., Results: Over 4197 chemotherapy cycles, 42.2% of patients experienced ≥grade 2 CINV. Eight risk factors were identified: patient age <60 years, the first two cycles of chemotherapy, anticipatory nausea and vomiting, history of morning sickness, hours of sleep the night before chemotherapy, CINV in the prior cycle, patient self-medication with non-prescribed treatments, and the use of platinum or anthracycline-based regimens. The ROC analysis indicated good predictive accuracy with an area-under-the-curve of 0.69 (95% CI: 0.67-0.70). Before to each cycle of therapy, patients with risk scores ≥16 units would be considered at high risk for developing ≥grade 2 CINV., Conclusions: The clinical application of this prediction tool will be an important source of individual patient risk information for the oncology clinician and may enhance patient care by optimizing the use of the antiemetics in a proactive manner., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology.)

Context: As endorsed by the palliative care "Measuring What Matters" initiative, capturing patients' direct assessment of their care is essential for ongoing quality reporting and improvement. Fostering an environment where seriously ill patients feel heard and understood is of crucial importance to modern health care., Objectives: To describe the development and performance of a self-report field measure for seriously ill patients to report how well they feel heard and understood in the hospital environment., Methods: As part of a larger ongoing cohort study of inpatient palliative care, we developed and administered the following point-of-care item: "Over the past two days, how much have you felt heard and understood by the doctors, nurses and hospital staff?" (completely, quite a bit, moderately, slightly, not at all). Participants completed the measure before and the day after palliative care consultation. For the postconsultation version, we changed the time frame from "past two days" to "today.", Results: One hundred sixty patients with advanced cancer completed the preconsultation assessment, and 87% of them completed the postconsultation version. Responses encompassed full use of the ordinal scale, did not exhibit ceiling or floor effects, and showed improvement from preassessment to postassessment. The item was quick to administer and easy for patients to complete., Conclusion: The "Heard & Understood" item is a promising self-report quality measure for the inpatient palliative care setting., (Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Chemotherapy-induced nausea and vomiting (CINV) is among the most feared and debilitating adverse events experienced by cancer patients. Left unaddressed, CINV symptoms not only decrease quality of life, but may also affect patients' willingness to continue chemotherapy treatment. Detailed guidelines are available that outline best practices for prophylaxis of acute and delayed CINV. However, adherence to guideline recommendations continues to be suboptimal, and many patients still suffer unnecessarily from CINV. In addition, breakthrough/refractory CINV continues to present particular challenges. The development of effective CINV treatments with diverse mechanisms of action has expanded the options available for preventing symptoms. The US Food and Drug Administration has recently approved several new therapies for the management of CINV. NEPA is a fixed-dose combination of netupitant(300 mg) plus palonosetron (0.5 mg). In combination with dexamethasone, NEPA has demonstrated superior efficacyto palonosetron alone in patients receiving highly or moderately emetogenic chemotherapy. Rolapitant is a next generation neurokinin 1 (NK1) receptor antagonist. Both palonosetron and rolapitant have proven particularly effective in controlling delayed CINV. Regimens that combine a serotonin 5-hydroxytryptamine–3 receptor antagonist, an NK1receptor antagonist, and a corticosteroid now represent the standard of care for managing both acute and delayed CINV in patients receiving highly emetogenic chemotherapy.

Background: Dignity Therapy is a brief psychotherapy that can enhance a sense of legacy while addressing the emotional and existential needs of patients receiving hospice or palliative care. In Dignity Therapy, patients create a formalized "legacy" document that records their most cherished memories, their lessons learned in life, as well as their hopes and dreams for loved ones in the future. To date, this treatment has been studied for its impact on mitigating distress within hospice and palliative care populations and has provided mixed results. This study will instead focus on whether Dignity Therapy enhances positive outcomes in this population., Methods/design: In this study, 90 patients with cancer receiving hospice or palliative care will complete a mixed-methods randomized controlled trial of Dignity Therapy (n = 45) versus Supportive Attention (n = 45). The patients will be enrolled in the study for 3 weeks, receiving a total of six study visits. The primary outcomes examine whether the treatment will quantitatively increase levels of positive affect and a sense of life closure. Secondary outcomes focus on gratitude, hope, life satisfaction, meaning in life, resilience, and self-efficacy. Using a fixed, embedded dataset design, this study will additionally use qualitative interviews to explore patients' perceptions regarding the use of positive outcome measures and whether these outcomes are appropriately matched to their experiences in therapy., Discussion: Dignity Therapy has shown mixed results when evaluating its impact on distress, although no other study to date has solely focused on the potential positive aspects of this treatment. This study is novel in its use of mixed methods assessments to focus on positive outcomes, and will provide valuable information about patients' direct experiences in this area., Trial Registration: ISRCTN91389194.

Purpose: Dermatologic adverse events (dAEs) in cancer treatment are frequent with the use of targeted therapies. These dAEs have been shown to have significant impact on health-related quality of life (HRQoL). While standardized assessment tools have been developed for physicians to assess severity of dAEs, there is a discord between objective and subjective measures. The identification of patient-reported outcome (PRO) instruments useful in the context of targeted cancer therapies is therefore important in both the clinical and research settings for the overall evaluation of dAEs and their impact on HRQoL., Methods: A comprehensive, systematic literature search of published articles was conducted by two independent reviewers in order to identify PRO instruments previously utilized in patient populations with dAEs from targeted cancer therapies. The identified PRO instruments were studied to determine which HRQoL issues relevant to dAEs were addressed, as well as the process of development and validation of these instruments., Results: Thirteen articles identifying six PRO instruments met the inclusion criteria. Four instruments were general dermatology (Skindex-16©, Skindex-29©, Dermatology Life Quality Index (DLQI), and DIELH-24) and two were symptom-specific (functional assessment of cancer therapy-epidermal growth factor receptor inhibitor-18 (FACT-EGFRI-18) and hand-foot syndrome 14 (HFS-14))., Conclusions: While there are several PRO instruments that have been tested in the context of targeted cancer therapy, additional work is needed to develop new instruments and to further validate the instruments identified in this study in patients receiving targeted therapies., Competing Interests: AND SOURCES OF FUNDING There were no sources of funding used in this study. The authors have full control of the primary data, which is available to the journal at their request for review. Dr. Roeland has a consultant role with Cellulitix. Dr. Choi has received remuneration from Onyx Pharmaceuticals and has a consultant role with Biotest AG. Dr. Bryce has a consultant role with AstraZeneca and Roche. Dr. Gerber has a consultant role with Galderma International. He is also receiving research funding from Hoffman La Roche. Dr. Lacouture has a consultant role with AstraZeneca, Roche, Bayer, Janssen, Exelixis, Advancell, BMS, Amgen, and Genentech. He is also receiving research funding from Berg, Roche and BMS.

Stem cell transplantation (SCT) and palliative care (PC) may initially appear to be distant extremes in the continuum of care of patients with hematologic malignancies, opposed by multiple obstacles preventing their integration. Rather, we will posit that both fields share many similarities and have much to learn from one another. PC has increasing relevance in cancer care given recent studies that link PC to improved quality-of-life, survival, and decreased cost of care. Understanding modern conceptualizations of PC and its role within SCT is key. Through the report of a single academic medical center experience with an integrated SCT and PC model over the last decade, we will discuss future opportunities for strengthening collaboration between SCT and PC. PC in SCT should be considered from the day of diagnosis and tied to need, not to prognosis., (© 2015 by The American Society of Hematology. All rights reserved.)

A 36-year-old female with metastatic breast cancer involving bones, liver, lung, and pleura/chest wall with worsening back pain received weight-based intravenous (IV) ketamine and was transitioned to oral ketamine for cancer-related neuropathic pain. She had responded poorly to outpatient pain regimen of oxycodone sustained and immediate release, hydromorphone, gabapentin, and duloxetine (approximate 480 mg total oral morphine equivalents [OME]), reporting an initial pain score of 10/10. She was started on hydromorphone parenteral patient-controlled analgesia (PCA) bolus dose in addition to her outpatient regimen. Despite escalating doses of opioids and the addition of a lidocaine 5% patch, the patient's pain remained uncontrolled 6 days after admission. On hospital day 7, utilizing a hospital weight-based ketamine protocol, the patient was started on subanesthetic doses of ketamine at 0.2 mg/kg/h (288 mg/24 h) and titrated over 2 days to 0.4 mg/kg/h (576 mg/24 h). Then, a 3-day rotation from intravenous to oral ketamine was initiated, and the patient was discharged on ketamine oral solution, 75 mg every 8 hours. When the patient's dose was increased to 0.4 mg/kg/h, adequate pain relief was charted by the nurse within 120 minutes, "patient pain free and resting comfortably." Her pain continued to be well managed, with an average pain score of 5/10 with the ketamine continuous infusion and sustained with conversion to oral ketamine without any report of side effects. This was a 37% reduction in pain scores. With the patient's stabilized dose of ketamine, opioid requirements decreased by 61.4% (1017.5 mg reduction in total OME). The use of weight-based dosing of IV continuous infusion and transition to oral ketamine was effective and tolerable in the management of opioid-refractory, neuropathic cancer pain. It is hoped that this case report promotes a discussion regarding ketamine dosing in refractory neuropathic cancer pain.

Abstract The balance between patient autonomy and medical paternalism must be reexamined. The tension between autonomy and paternalism is both an ethical and practical issue. Autonomy is the current gold standard approach to patient communication and has grown to the point that patient preference dictates care, even when their choices are not possible or are medically nonbeneficial. Furthermore, we have observed a trend among physicians to avoid making difficult medical decisions by hiding behind a shield of patient autonomy. Paternalism, characterized as the antithesis of autonomy, is widely dismissed as having any role in medicine. We disagree and believe that paternalism still has an important role in medical decision making.

Allergic transfusion reactions (ATRs) are a common complication of blood transfusions. Advances in transfusion medicine have significantly decreased the incidence of ATRs; however, ATRs continue to be burdensome for patients and problematic for providers who regularly order packed red blood cells and platelet transfusions. To further decrease the frequency of ATRs, routine premedication with diphenhydramine is common practice and is part of "transfusion culture" in a majority of institutions. In this article, we review the history, practice, and literature of transfusion premedication, specifically antihistamines given the adverse-effect profile. We discuss the rationale and original academic studies, which have supported the use of premedication for transfusions for decades. However, despite the common use of premedication to prevent ATRs, recent literature has not conclusively validated its use. In addition, the existing premedication that is routinely prescribed often causes a number of adverse effects. These findings have motivated the Moores Cancer Center (University of California, San Diego) to change its current transfusion premedication practices, particularly with regard to ATRs and first-generation antihistamines. We outline the preliminary development of an evidence-based and patient-specific approach to transfusion premedication, including the challenges and steps taken to revise inpatient premedication protocols. We plan to expand this protocol to the outpatient setting at a later date. Future efforts require a prospective validation of our presented transfusion premedication guidelines.

Background: Medical management is the cornerstone of malignant bowel obstruction (MBO) therapy and may include antisecretory agents such as octreotide. Currently, no data exist regarding octreotide prescribing patterns in US academic hospitals in the palliation of inoperable MBO. The aim of this study is to collect octreotide prescribing data to shape future prospective studies., Methods: This retrospective chart review evaluated inpatient inoperable MBO admissions at a single academic US hospital between 2008 and 2011. The prescribing primary service (medical vs. surgical), inpatient day initiated, average octreotide daily dose, cumulative octreotide dose, days receiving octreotide, length of stay (LOS), subject age, cancer stage, lines of chemotherapy, cancer type, and overall survival were analyzed utilizing a Wilcoxon rank sum test, Spearman rank correlation test, Kaplan-Meier curves, log rank test, and multiple linear regression analysis when appropriate., Results: A total of 767 patients received octreotide. A cancer diagnosis was documented in 134 patients and 37 of these (24 females and 13 males; mean age, 56.7 years) had a confirmed inoperable MBO. Statistical significance was not achieved for variables analyzed. However, octreotide prescribing trends were observed for several variables: the mean LOS was equivalent on both services (16.8 vs. 17 days), mean octreotide dose was higher on the medical service (201.2 μg vs. 119 μg surgical), cumulative octreotide dose was higher on the medical service (3,558 vs. 1,884 mcg), mean day of octreotide initiation was roughly equivalent (7.9 days medical vs. 8.8 days surgical), subjects on the medical service had a decreased overall survival, and earlier octreotide initiation (defined as <7 days) was associated with a decreased overall survival., Limitation: The data were collected retrospectively, with a limited population distribution at a specific time., Conclusions: These data possibly suggest that the MBO patients on the medical vs. surgical services are distinct patient populations. MBO patients on the medical service trended to receive higher cumulative doses and have a decreased overall survival compared with surgical patients. Consequently, future studies should possibly consider these distinct study groups.

Stem cell transplantation (SCT) offers a potential cure for patients with otherwise incurable benign and malignant disorders. However, the treatment will cause considerable physical, social, psychological, and spiritual suffering. In part 1 of this review, the management of the physical symptoms was reviewed. In part 2, we discuss the approaches to managing the other aspects of distress that are primarily psychological, social, and spiritual in nature. In practice, these dimensions are not so easily distinguished; the division between physical and psychological symptoms is blurred, and physical symptoms are often interrelated with the patient's emotional status and social support.

Stem cell transplantation (SCT) offers a potential cure for patients with otherwise incurable benign and malignant disorders, but the arduous SCT process may cause considerable physical, social, psychological, and spiritual suffering. Relief of suffering associated with SCT begins by understanding the patient experience and the SCT culture. Symptom burden is the combined impact of all disease- or therapy-related symptoms on the patient's ability to function. In approaching symptom management, the division between physical and psychological symptoms is blurred; physical symptoms are often interrelated with the patient's emotional status and social support. Physical symptoms that frequently occur in SCT include pain, nausea, mucositis, diarrhea, and delirium. At the same time, SCT is recognized as one of the most stressful treatments in modern cancer care, resulting in psychological distress, social isolation, and role changes. Psychological symptoms include depression/ anxiety, grief/loss, demoralization, and anger. Based on our experience on an academic SCT ward for adults, we review physical, psychological, social, and spiritual symptoms during the course of SCT in a two-part series and offer an approach to their management. This month, in part I, we focus on physical symptoms linked to SCT. In a future issue, part II will highlight psychosocial concerns in SCT.

Malignant bowel obstruction (MBO) is a challenging complication of advanced cancer. Several pathophysiologic mechanisms are responsible for the syndrome, including mechanical compression, motility disorders, gastrointestinal secretion accumulation, decreased gastrointestinal absorption, and inflammation. The treatment of related symptoms requires a collaborative approach of surgical, interventional, and medical specialists. The surgical approach proves beneficial in selected patients with operable lesions, life expectancy greater than 2 months, and good performance status. Interventionalists place self-expanding metallic stents as a minimally invasive palliative method either as a definitive treatment or as a bridge to surgery. However, most patients with MBO are not candidates for surgery or stent placement. Medical management with opioids, antispasmodics, antiemetics, antisecretory agents, and corticosteroids is effective in controlling the symptoms associated with MBO. This article discusses the current understanding of MBO pathophysiology and emphasizes current MBO management concepts; it then reviews surgical, interventional, and medical approaches.