Judith A. Paice

American Society of Clinical Oncology Provisional Clinical Opinion: The Integration of Palliative Care Into Standard Oncology Care

PURPOSE An American Society of Clinical Oncology (ASCO) provisional clinical opinion (PCO) offers timely clinical direction to ASCOs membership following publication or presentation of potentially practice-changing data from major studies. This PCO addresses the integration of palliative care services into standard oncology practice at the time a person is diagnosed with metastatic or advanced cancer. CLINICAL CONTEXT Palliative care is frequently misconstrued as synonymous with end-of-life care. Palliative care is focused on the relief of suffering, in all of its dimensions, throughout the course of a patients illness. Although the use of hospice and other palliative care services at the end of life has increased, many patients are enrolled in hospice less than 3 weeks before their death, which limits the benefit they may gain from these services. By potentially improving quality of life (QOL), cost of care, and even survival in patients with metastatic cancer, palliative care has increasing relevance for the care of patients with cancer. Until recently, data from randomized controlled trials (RCTs) demonstrating the benefits of palliative care in patients with metastatic cancer who are also receiving standard oncology care have not been available. RECENT DATA Seven published RCTs form the basis of this PCO. PROVISIONAL CLINICAL OPINION Based on strong evidence from a phase III RCT, patients with metastatic non-small-cell lung cancer should be offered concurrent palliative care and standard oncologic care at initial diagnosis. While a survival benefit from early involvement of palliative care has not yet been demonstrated in other oncology settings, substantial evidence demonstrates that palliative care-when combined with standard cancer care or as the main focus of care-leads to better patient and caregiver outcomes. These include improvement in symptoms, QOL, and patient satisfaction, with reduced caregiver burden. Earlier involvement of palliative care also leads to more appropriate referral to and use of hospice, and reduced use of futile intensive care. While evidence clarifying optimal delivery of palliative care to improve patient outcomes is evolving, no trials to date have demonstrated harm to patients and caregivers, or excessive costs, from early involvement of palliative care. Therefore, it is the Panels expert consensus that combined standard oncology care and palliative care should be considered early in the course of illness for any patient with metastatic cancer and/or high symptom burden. Strategies to optimize concurrent palliative care and standard oncology care, with evaluation of its impact on important patient and caregiver outcomes (eg, QOL, survival, health care services utilization, and costs) and on society, should be an area of intense research. NOTE ASCOs provisional clinical opinions (PCOs) reflect expert consensus based on clinical evidence and literature available at the time they are written and are intended to assist physicians in clinical decision making and identify questions and settings for further research. Because of the rapid flow of scientific information in oncology, new evidence may have emerged since the time a PCO was submitted for publication. PCOs are not continually updated and may not reflect the most recent evidence. PCOs cannot account for individual variation among patients and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It is the responsibility of the treating physician or other health care provider, relying on independent experience and knowledge of the patient, to determine the best course of treatment for the patient. Accordingly, adherence to any PCO is voluntary, with the ultimate determination regarding its application to be made by the physician in light of each patients individual circumstances. ASCO PCOs describe the use of procedures and therapies in clinical trials and cannot be assumed to apply to the use of these interventions in the context of clinical practice. ASCO assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of ASCOs PCOs, or for any errors or omissions.

Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline

PURPOSE To provide evidence-based guidance on the optimum prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathies (CIPN) in adult cancer survivors. METHODS A systematic literature search identified relevant, randomized controlled trials (RCTs) for the treatment of CIPN. Primary outcomes included incidence and severity of neuropathy as measured by neurophysiologic changes, patient-reported outcomes, and quality of life. RESULTS A total of 48 RCTs met eligibility criteria and comprise the evidentiary basis for the recommendations. Trials tended to be small and heterogeneous, many with insufficient sample sizes to detect clinically important differences in outcomes. Primary outcomes varied across the trials, and in most cases, studies were not directly comparable because of different outcomes, measurements, and instruments used at different time points. The strength of the recommendations is based on the quality, amount, and consistency of the evidence and the balance between benefits and harms. RECOMMENDATIONS On the basis of the paucity of high-quality, consistent evidence, there are no agents recommended for the prevention of CIPN. With regard to the treatment of existing CIPN, the best available data support a moderate recommendation for treatment with duloxetine. Although the CIPN trials are inconclusive regarding tricyclic antidepressants (such as nortriptyline), gabapentin, and a compounded topical gel containing baclofen, amitriptyline HCL, and ketamine, these agents may be offered on the basis of data supporting their utility in other neuropathic pain conditions given the limited other CIPN treatment options. Further research on these agents is warranted.

Validity of a verbally administered numeric rating scale to measure cancer pain intensity

The ability to quantify pain intensity is essential when caring for individuals in pain in order to monitor patient progress and analgesic effectiveness. Three scales are commonly employed: the simple descriptor scale (SDS), the visual analog scale (VAS), and the numeric (pain intensity) rating scale (NRS). Patients with English as a second language may not be able to complete the SDS without translation, and visually, cognitively, or physically impaired patients may have difficulty using the VAS. The NRS has been found to be a simple and valid alternative in some disease states; however, the validity of this scale administered verbally, without visual cues, to oncology patients has not yet been established. The present study examined validity of a verbally administered 0-10 NRS using convergence methods. The correlation between the VAS and the NRS was strong and statistically significant (r = 0.847, p < 0.001), supporting the validity of the verbally administered NRS. Although all subjects were able to complete the NRS and SDS without apparent difficulty, 11 subjects (20%) were unable to complete the VAS. The mean opioid intake was significantly higher for the group that was unable to complete the VAS (mean 170.8 mg, median 120.0 mg, SD = 135.8) compared to the group that had no difficulty with the scale (mean 65.6 mg, 33.0 mg, SD = 99.7) (Mann-Whitney test, p = 0.0065). The verbally administered 0-10 NRS provides a useful alternative to the VAS, particularly as more contact with patients is established via telephone and patients within the hospital are more acutely ill.

Intraspinal morphine for chronic pain : A retrospective, multicenter study

Intraspinal opioids are frequently used in the treatment of cancer and noncancer pain, but few studies have evaluated the efficacy of this technique. This multicenter, retrospective study surveyed physicians in the United States regarding their standard practices when using intraspinal opioids delivered via an implanted drug administration device. Thirty-five physicians (50.0%) responded, providing 429 usable patient forms (52.4%), which sought information about screening, outcomes, dosing, and adverse effects. Patients with malignant (32.7%) and noncancer (67.3%) pain had been treated for an average of 14.6 +/- 0.57 months (range, 8-94 months) at the time of form completion. For all patients, the mean percent relief was 61.0% +/- 1.35%. Patients with somatic pain tended to have greater relief, as measured by a global rating of pain relief, than did patients with other types of pain (Mann-Whitney test, P = 0.0003). After titration during the first 3 months, intrathecal morphine doses increased only twofold from 6.84 +/- 0.65 mg/day at 3 months to 13.19 +/- 1.76 mg/day at 24 months. Compared to those with noncancer pain, malignant pain patients had a higher average initial dose. The average dose used by cancer patients escalated quickly and then stabilized, whereas the average doses used by noncancer pain patients exhibited a more gradual, linear increase in dose. Long-term adverse drug effects were uncommon, but system malfunction, usually catheter related, occurred in 21.6% of patients. Prospective, randomized, controlled clinical studies of long-term efficacy and adverse effects are warranted.

Integration of Palliative Care Into Standard Oncology Care: American Society of Clinical Oncology Clinical Practice Guideline Update

Purpose To provide evidence-based recommendations to oncology clinicians, patients, family and friend caregivers, and palliative care specialists to update the 2012 American Society of Clinical Oncology (ASCO) provisional clinical opinion (PCO) on the integration of palliative care into standard oncology care for all patients diagnosed with cancer. Methods ASCO convened an Expert Panel of members of the ASCO Ad Hoc Palliative Care Expert Panel to develop an update. The 2012 PCO was based on a review of a randomized controlled trial (RCT) by the National Cancer Institute Physicians Data Query and additional trials. The panel conducted an updated systematic review seeking randomized clinical trials, systematic reviews, and meta-analyses, as well as secondary analyses of RCTs in the 2012 PCO, published from March 2010 to January 2016. Results The guideline update reflects changes in evidence since the previous guideline. Nine RCTs, one quasiexperimental trial, and five secondary analyses from RCTs in the 2012 PCO on providing palliative care services to patients with cancer and/or their caregivers, including family caregivers, were found to inform the update. Recommendations Inpatients and outpatients with advanced cancer should receive dedicated palliative care services, early in the disease course, concurrent with active treatment. Referral of patients to interdisciplinary palliative care teams is optimal, and services may complement existing programs. Providers may refer family and friend caregivers of patients with early or advanced cancer to palliative care services.

Adverse effects associated with the intrathecal administration of ziconotide

The omega-conopeptide, ziconotide, is an N-type calcium-channel blocker that has been shown to produce antinociception in animals using formalin and hot-plate tests. Initial reports of intrathecal administration of ziconotide in cancer and AIDS patients whose pain was unrelieved with opioids demonstrated analgesic efficacy. Although adverse effects were reported, these appeared to be easily managed through dose reduction or symptomatic treatment. This clinical report describes the experiences of three patients with serious adverse effects associated with intrathecal ziconotide.

Barriers to Cancer Pain Relief: Fear of Tolerance and Addiction

The purposes of this study were to (a) test the feasibility of the Cancer Total Quality Pain Management (TQPM) Patient Assessment Tool in a population of oncology inpatient and outpatients; and (b) identify factors associated with poor pain relief. The Cancer TQPM Tool was adapted from the American Pain Societys Quality Assurance Standards on Acute Pain and Cancer Pain and was tested in a convenience sample of 200 patients. The majority of patients reported that the TQPM Tool was easy to understand and to use, providing evidence for the feasibility of the tool. Factors associated with higher pain intensity included the inpatient setting, the presence of metastatic disease, hesitancy in bothering the nurse, and concerns regarding tolerance and addiction. Although there was a strong relationship between concern about addiction and concern about tolerance, fear of tolerance appeared to have a greater effect on pain intensity scores than did fear of addiction. The findings from this study suggest that the Cancer TQPM Patient Assessment Tool can be used effectively in both inpatients and outpatients to determine outcomes and the quality of cancer pain management, as well identify factors associated with poor pain control. Clinical implications include more effective education of patients and caregivers, including equivalent emphasis on tolerance and addiction.

Brain activity for spontaneous pain of postherpetic neuralgia and its modulation by lidocaine patch therapy

Abstract Postherpetic neuralgia (PHN) is a debilitating chronic pain condition, yet there is a lack of knowledge regarding underlying brain activity. Here we identify brain regions involved in spontaneous pain of PHN (n = 11) and determine its modulation with Lidoderm therapy (patches of 5% lidocaine applied to the PHN affected body part). Continuous ratings of fluctuations of spontaneous pain during fMRI were contrasted to ratings of fluctuations of a bar observed during scanning, at three sessions: (1) pre‐treatment baseline, (2) after 6 h of Lidoderm treatment, and (3) after 2 weeks of Lidoderm use. Overall brain activity for spontaneous pain of PHN involved affective and sensory‐discriminative areas: thalamus, primary and secondary somatosensory, insula and anterior cingulate cortices, as well as areas involved in emotion, hedonics, reward, and punishment: ventral striatum, amygdala, orbital frontal cortex, and ventral tegmental area. Generally, these activations decreased at sessions 2 and 3, except right anterior insular activity which increased with treatment. The sensory and affective activations only responded to the short‐term treatment (6 h of Lidoderm); while the ventral striatum and amygdala (reward‐related regions) decreased mainly with longer‐term treatment (2 weeks of Lidoderm). Pain properties: average magnitude of spontaneous pain, and responses on Neuropathic Pain Scale (NPS), decreased with treatment. The ventral striatal and amygdala activity best reflected changes in NPS, which was modulated only with longer‐term treatment. The results show a specific brain activity pattern for PHN spontaneous pain, and implicate areas involved in emotions and reward as best reflecting changes in pain with treatment.

Core competencies for pain management: Results of an interprofessional consensus summit

Objective The objective of this project was to develop core competencies in pain assessment and management for prelicensure health professional education. Such core pain competencies common to all prelicensure health professionals have not been previously reported. Methods An interprofessional executive committee led a consensus-building process to develop the core competencies. An in-depth literature review was conducted followed by engagement of an interprofessional Competency Advisory Committee to critique competencies through an iterative process. A 2-day summit was held so that consensus could be reached. Results The consensus-derived competencies were categorized within four domains: multidimensional nature of pain, pain assessment and measurement, management of pain, and context of pain management. These domains address the fundamental concepts and complexity of pain; how pain is observed and assessed; collaborative approaches to treatment options; and application of competencies across the life span in the context of various settings, populations, and care team models. A set of values and guiding principles are embedded within each domain. Conclusions These competencies can serve as a foundation for developing, defining, and revising curricula and as a resource for the creation of learning activities across health professions designed to advance care that effectively responds to pain.

Antinociception induced by electrical stimulation of spinally projecting noradrenergic neurons in the A7 catecholamine cell group of the rat

&NA; Recent anatomical evidence indicates that the pontine A7 catecholamine cell group provides the major noradrenergic innervation of the spinal cord dorsal horn (laminae I–IV). The experiments described in this report were designed to determine if these neurons modulate nociception at the level of the spinal cord. To this end, the antinociceptive effect of electrical stimulation applied at various sites along several tracks through the dorsolateral pontine tegmentum was determined in lightly anesthetized rats. The latency of the withdrawal response of the hind feet to noxious radiant thermal stimulation applied to the dorsal surface was used as a measure of nociception. The results indicated that the most potent and consistent antinociception was produced at sites near the A7 cell group. In addition, intrathecal injection of &agr;‐noradrenergic antagonists blocked the antinociception produced by electrical stimulation at sites near the A7 group. These observations indicate that the antinociception produced by stimulation near the A7 cell group was mediated by spinally projecting noradrenergic neurons. The results of these experiments provide evidence that pontospinal noradrenergic neurons located in the A7 cell group are important components of the descending neuronal system that modulates nociception.