Breanne Lechner

Cut points for mild, moderate, and severe pain among cancer and non-cancer patients: a literature review

Defining cut points (CPs) for varying levels of pain intensity is important for assessing changes in patients functional status, and guiding the development and evaluation of treatment options. We aimed to summarize CPs identified in the literature for mild, moderate, and severe pain on the numeric rating scale (NRS), and recommend optimal CPs for cancer and non-cancer patients. We searched MEDLINE and EMBASE (inception to May 2015) for studies that used CPs to classify pain intensity on the NRS among patients with cancer or non-cancer conditions leading to acute or chronic pain. A CP was defined as the upper bound of a mild or moderate pain category. Of 1,556 identified articles, 27 were included for review. Among patients with cancer pain, mild-moderate pain CPs ranged from 1 to 4 (mean, 3.5±1.08), with CP4 being the most recommended CP (80%). For moderate-severe pain, CPs ranged from 4 to 7 (mean, 6.2±0.92), and CP6 (50%) was the optimal CPs. Among patients with non-cancer pain, mild-moderate pain CPs ranged from 2 to 5 (mean, 3.62±0.78), and CP4 was the most frequently used CP (52.9%). For moderate-severe non-cancer pain, CPs ranged from 4 to 8 (mean, 6.5±0.99), and CP6 (41.2%) was the most frequently recommended CP. A wide range of CPs for mild, moderate, and severe pain categories were identified in the literature among both cancer and non-cancer patient populations. Further studies are needed to delineate more accurate and precise CPs for pain intensity.

Does Pregabalin Still Have a Role in Treating Cancer-Induced Bone Pain?

Bone metastases are common in patients with advanced cancer and often cause cancer-induced bone pain (CIBP), which can significantly affect patients’ quality of life. Although radiotherapy is effective for CIBP, many patients do not attain complete relief of their symptoms after treatment. In the article that accompanies this editorial, Fallon et al conducted a randomized controlled trial (RCT) evaluating the efficacy of pregabalin in patients receiving radiotherapy for CIBP. A total of 233 patients were randomized to either pregabalin or placebo. There was no statistically significant difference in treatment response, defined as reduction in worst pain with stable or reduced opioid dose, average pain, pain interference, and quality of life between the two arms. Fallon et al concluded that the routine use of pregabalin in patients receiving radiotherapy for CIBP is not warranted. We applaud the investigators for their efforts but caution readers about two important issues in the design of the trial that may limit the generalizability of the study results. One issue is whether the study targeted the right patients. Pregabalin is a drug that binds to the a2-d subunit of calcium channels and there is evidence from reported RCTs supporting its use in neuropathic pain caused by diabetic peripheral neuropathy (DPN), postherpetic neuralgia (PHN), spinal cord injury, and fibromyalgia. Per the pregabalin product monograph, these conditions are the recommended indications for its use as an analgesic. Given its proven effectiveness in treating the aforementioned conditions, pregabalin is also prescribed for neuropathic and nonneuropathic CIBP as an off-label indication. Although there is preclinical evidence in animal models that CIBP is responsive to neuropathic agents, the only RCT investigating the efficacy of pregabalin in CIBP was terminated early because an interim analysis revealed that the study was underpowered to show the intended treatment effect. Thus, the role of pregabalin in the treatment of all neuropathic and nonneuropathic CIBP remains to be determined. The Fallon et al trial excluded patients who were already receiving pregabalin or gabapentin; this would eliminate patients with neuropathic pain features, because many of these patients would be started on neuropathic agents already. These excluded patients are, in fact, the ideal target group who would potentially benefit the most from pregabalin. It is unclear how many of the enrolled patients had a neuropathic component to their CIBP, because this was not formally assessed or documented. The estimated incidence of neuropathic pain features in patients receiving palliative radiotherapy to bonemetastases is 17% to 20% and the incidence of neuropathic pain in the Fallon et al study would be even lower. If pregabalin were more effective in CIBP with neuropathic features, its true treatment effect would have been underestimated as a result of potential exclusion from this trial. Of 1,970 patients screened in the study, 1,737 were excluded because they did not meet the inclusion criteria. Only 233 patients were randomized and the trial failed to meet its target accrual of 260 patients. Given that 88% of the screened patients were excluded and the difficulty with accrual, leading to early termination, the generalizability of the trial result is limited. The second issue is whether the study captured the right end points. The primary end point of the trial was a reduction of two or more points on a 0 to 10 numerical rating scale (NRS) for worst pain measured at 4 weeks, accompanied by a stable or reduced opioid medication dose, compared with baseline. However, previous studies have shown that a significant portion of patients with CIBP will respond to radiotherapy after 4 weeks. The Bone Pain Trial from the United Kingdom showed that 1 month after randomization, only 54% of patients in the single 8-Gy arm had an improvement in pain relief. However, 8 weeks and 12 weeks following randomization, 68% and 75% of patients had an improvement in pain relief, respectively. Similarly, the Dutch Bone Metastasis Study showed that 4 weeks after randomization, the mean pain score in the single 8-Gy arm decreased from 7.2 to 5.1. However, 8 weeks and 12 weeks following randomization, the mean pain score further decreased to 4.2 and 3.9, respectively. Therefore, the end point at 4 weeks does not appear to capture the full treatment effect of radiotherapy. In the only radiation trial that selectively included patients with neuropathic pain, a fractionated course of radiotherapy (20 Gy in five fractions) might have been more effective than a single-fraction treatment, although the results were not statistically significant. The investigators suggested a dose-escalation trial of 30 Gy versus 8 Gy for further investigation. In the Fallon et al study, both 8 Gy in one fraction and 20 Gy in five fractions were allowed. Given the uncertainty in the optimal radiation prescription parameters for neuropathic pain, radiation dose should ideally be stratified in the analysis.

Psychometric validation of the Brain Symptom and Impact Questionnaire (BASIQ) version 1.0 to assess quality of life in patients with brain metastases

OBJECTIVE To test the reliability, clinical and psychometric validity of the Brain Symptom and Impact Questionnaire (BASIQ) in patients with brain metastases. METHODS Brain metastases patients were interviewed using the BASIQ, Functional Assessment of Cancer-Brain (FACT-Br) and FACT-General (FACT-G) at baseline, with a follow-up assessment at 1 month. RESULTS Forty patients had complete one data and the median age was 64 years. Patients with higher KPS, ECOG of 2, primary breast cancer, or >3 brain metastases, scored higher on the symptom scale of the BASIQ. All subscales showed no significant change in patient symptoms from baseline to follow-up. CONCLUSION This study supports that the reliability, clinical and psychometric validity of BASIQ to be used in brain metastases patients.

Re-irradiation for painful bone metastases: evidence-based approach

The prognosis of patients with bone metastases has improved with the advent of increasingly effective systemic treatment and better supportive care. A growing number of bone metastases patients now outlive the duration of benefits from their initial treatment of radiotherapy (RT) while some patients fail to initially respond to RT. As such, re-irradiation (re-RT) may be required. The current review updates the literature on findings in the area of re-RT. In particular, the recent publication of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) Symptom Control (SC20) trial shows that an 8 Gy treatment in a single fraction for re-RT is non-inferior and less toxic than 20 Gy in multiple fractions. Furthermore, patients responding to re-RT have experienced superior quality of life (QoL) and complain of less functional interference from pain; this provides a strong case in support of bone metastases patients being offered re-treatment. However, despite such findings, some specific patients will never respond to initial radiation or re-RT. New evidence suggests significant differences in bone markers between responders and non-responders, thus opening the possibility for further research into the use of such biomarkers for predicting prognosis and for the guidance of consequent treatment decisions.

Latest advances in the management of radiation-induced pain flare, nausea and vomiting

Palliative radiotherapy (RT) is an effective treatment for symptomatic bone metastases. However, pain flare, nausea and vomiting are common adverse effects associated with this treatment. The management of pain flare and radiation-induced nausea and vomiting (RINV) are important endpoints in palliative care. Our report documents the incidence, clinical importance, and advances in the management of these two adverse-effects. We recommend that antiemetic prophylaxis be given based on emetic risk category as outlined in the American Society of Clinical Oncology (ASCO) guidelines. Newer antiemetics investigated in the chemotherapy setting should also be studied in the radiation setting. As there are no guidelines for the use of pain flare prophylaxis at present, further research in this area is needed.

Comparison of the EORTC STO-22 and the FACT-Ga quality of life questionnaires for patients with gastric cancer

This review compares the development, characteristics, validity, and reliability of two well-known quality of life (QOL) assessment tools used in patients with gastric cancer: the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Stomach (EORTC QLQ-STO22) and the Functional Assessment of Cancer Therapy-Gastric (FACT-Ga). A literature search was conducted using MEDLINE, EMBASE, and Cochrane CENTRAL (inception to April 2015) to identify studies that discussed the development, characteristics, validity and reliability of the EORTC QLQ-STO22 or the FACT-Ga. The QLQ-STO22 was developed with collaboration with patients, healthcare professionals and literature review and was mainly field tested in European countries. Conversely, items on the FACT-Ga were generated from interviews with patients and healthcare professionals concurrently in North America and Asia. While both modules involve a 7-day recall period and use Likert scales, the QLQ-STO22 and FACT-Ga differ in terms of QOL domain focus, quantity and presentation of items, response options, and scoring. However, both tools show good internal consistency, test-retest reliability, sensitivity to change and construct validity. In addition, both questionnaires have been internationally validated within a large sample of patients undergoing a variety of treatments, thus demonstrating their cross-cultural applicability. The EORTC QLQ-STO22 and FACT-Ga are both valid and reliable tools with unique strengths and weaknesses. Selection between instruments should consider specific patient characteristics and goals of the study.

Olanzapine for the prophylaxis and rescue of chemotherapy-induced nausea and vomiting (CINV): a retrospective study

BACKGROUND While the efficacy of olanzapine in the prophylaxis of chemotherapy-induced nausea and vomiting (CINV) has been documented, the literature on the use of olanzapine as a rescue medication for breakthrough CINV has been scarce. The following study retrospectively evaluated the safety and efficacy of olanzapine for the treatment of breakthrough CINV. The efficacy and safety of olanzapine in the prophylactic setting was also examined in a smaller cohort. METHODS Electronic medical records of adult patients aged >17 years receiving a prescription for olanzapine from the Odette Cancer Centre Pharmacy at Sunnybrook Hospital between January 2013 and June 2015 were reviewed retrospectively. Inclusion criteria required receiving one or more doses of olanzapine for the rescue or prophylaxis of CINV and documentation of the outcome. RESULTS A total of 154 patients and 193 treatment cycles were included in the breakthrough setting, while a total of 16 patients and 20 treatment cycles were included in the prophylaxis setting. In the breakthrough setting, 88% of cases experienced improved nausea, while 21% of cases reported improved vomiting. In the prophylactic setting, 100% of cases experienced improved nausea, while 65% achieved improved vomiting. A total of 43% of cases in the breakthrough setting and 65% of cases in the prophylactic setting experienced sedation. CONCLUSIONS Olanzapine is effective in improving CINV in both the prophylactic and breakthrough settings. The safety, efficacy, and appropriate dosage of olanzapine for the rescue of breakthrough CINV should be prospectively evaluated in a randomized controlled trial (RCT).

The Brain Symptom and Impact Questionnaire in brain metastases patients: a prospective long-term follow-up study

AIMS To assess the ability of the Brain Metastases Symptom and Impact Questionnaire (BASIQ) in evaluating symptoms and impact on daily life. PATIENTS & METHODS Patients with brain metastases completed BASIQ, Functional Assessment of Cancer Therapy-General, FACT-Brain at baseline and at 1, 2 and 3 months follow-ups. RESULTS Thirty-six patients completed all follow-ups. BASIQ correlated well (r ≥ 0.40) with FACT subscales, except for social/family and emotional wellbeing. Linear regression analysis found no significant changes in quality of life (QOL) over time in both the BASIQ and FACT scales. Therefore, the two questionnaires coincide as both detected nonchanges. CONCLUSION The ability of the BASIQ in evaluating symptoms and impact on over longer assessment periods was supported by the FACT questionnaires.

Challenges of Bone Metastases Treatment in Elderly Patients

Cancer rates are increasing, with the majority of cancer patients being over the age of 65. As the global population ages and life expectancies increase, the number of elderly patients requiring treatment also increases, thus the added challenges of treating elderly patients need to be addressed. This chapter outlines the challenges of palliative radiotherapy for elderly patients with bone metastases. We will begin with defining the term elderly, and outline the recent demographic details of patients with cancer. An update on the current status of elderly patients in clinical trials and discussion of factors that may affect enrolment of these patients into trials will be given. With an emphasis on palliative clinical trials, we will discuss methods to promote accrual of elderly patients in this setting. A review of the safety and efficacy of treatment in the elderly is also given, and palliative radiotherapy for the treatment of elderly patients with bone metastases is determined to be an advisable treatment and should be recommended to patients regardless of age. Physical burden of treatment in elderly patients can be alleviated by hypofractionated treatments, as multiple trials and meta-analyses have demonstrated their equivalence in pain control. In elderly patients, palliative radiotherapy may be more beneficial than other treatment options, as opioid-related adverse events are greater in this population. Physicians should continue to encourage elderly participation in clinical trials as this data forms the basis of treatment guidelines. Radiation oncologists are encouraged to offer elderly patients single treatments for bone metastases to reduce the physical burden of multiple treatments.