Delaying skeletal-related events in a randomized phase 3 study of denosumab versus zoledronic acid in patients with advanced cancer: an analysis of data from patients with solid tumors

Purpose

Bone complications of metastatic disease, including skeletal-related events (SREs), impair patients' functioning and quality of life. In a randomized, phase 3 trial of 1,776 patients with metastases from solid tumors (except breast or prostate) or multiple myeloma, denosumab was non-inferior to zoledronic acid (ZA) in delaying or preventing SREs. This ad hoc analysis reports outcomes in the subgroup of 1,597 patients with solid tumors, excluding patients with multiple myeloma.

Methods

Patients received monthly subcutaneous denosumab 120 mg or intravenous ZA 4 mg, adjusted for creatinine clearance, with calcium and vitamin D supplementation recommended. Endpoints included times to first on-study SRE, first-and-subsequent SREs, and pain worsening.

Results

Denosumab significantly delayed time to first on-study SRE compared with ZA (HR, 0.81; 95 % CI, 0.68–0.96) and time to first-and-subsequent SREs (RR, 0.85; 95 % CI, 0.72–1.00). Denosumab also significantly delayed time to development of moderate or severe pain (HR, 0.81; 95 % CI, 0.66–1.00), pain worsening (HR, 0.83; 95 % CI, 0.71–0.97), and worsening pain interference in patients with no/mild baseline pain (HR, 0.77; 95 % CI, 0.61–0.96). Adverse event rates were 96 % in both groups. Grade 3 or 4 hypocalcemia, mostly without clinical sequelae, was more frequent in denosumab-treated patients (denosumab 4 %, ZA 2 %). Osteonecrosis of the jaw occurred infrequently (denosumab 0.8 %, ZA 1.1 %).

Conclusions

Denosumab was more effective in delaying or preventing SREs in patients with bone metastases from solid tumors and also prevented pain progression compared to ZA in this ad hoc analysis.     

Patients with bone metastases from solid tumors initiating treatment with a bone-targeted agent in 2011: a descriptive analysis using oncology clinic data in the US

Purpose

Three bone-targeted agents (BTAs) are approved in the USA for prevention of bone complications among solid tumor patients with bone metastases: two intravenous bisphosphonates (IV BP) (pamidronate and zoledronic acid), and one subcutaneous receptor activator of nuclear factor-kappaB (RANK) ligand inhibitor (denosumab). Using electronic medical record data from outpatient community and hospital-affiliated oncology clinics, we examined the characteristics of patients who initiated treatment with a BTA in 2011 and followed them for a maximum of 12 months.

Methods

Adult patients with bone metastasis secondary to solid tumors newly treated with a BTA during 2011 were identified from the Oncology Services Comprehensive Electronic Records (OSCER) database. We examined patient characteristics at BTA initiation, treatment patterns, and compliance during a 12-month period. Sensitivity analyses were performed in a subgroup of patients who had confirmed 12 months of follow-up data.

Results

Denosumab patients (N?=?1,594) were older (65 % ≥65 years vs. 60 % ≥65 years), further along in their disease progression (time since bone metastasis diagnosis: 16 % ≥2 years vs. 10 % ≥2 years), less likely to switch BTA (overall: 6 vs. 14 %; subgroup: 8 vs. 19 %), and more compliant with treatment (overall: median doses of 7 vs. 4; subgroup: 11 vs. 8) compared to IV BP patients (N?=?1,975). Findings were consistent across gender, age, tumor type, naïve, and transition strata.

Conclusions

Patients receiving denosumab and IV BPs may differ. Despite higher age and more advanced disease, patients treated with denosumab are more likely to stay on treatment and have better compliance.     

Reducing the burden of bone metastases

Background

Bone metastases occur frequently in patients with solid tumours such as those of the prostate, breast and lung, and are associated with an increased risk of skeletal-related events (SREs). This article reviews the personal, social and economic burdens of bone metastases and SREs, and approaches to treatment.

Methods

PubMed searches were conducted using a broad range of search terms. Articles identified were refined by author review of abstracts. Additional material was identified by searching recent relevant congress abstracts.

Results

Bone metastases often decrease quality of life, but quantitative data on the extent of this effect are limited. Data from the USA demonstrate a significant financial burden associated with bone metastases; similar trends are now being uncovered in Europe as the number of assessments of health economics and healthcare resource utilisation in the region increases. The bisphosphonate zoledronic acid reduces the incidence of SREs compared with placebo. Recent phase 3 studies have shown that therapy with the RANK ligand inhibitor denosumab is superior to zoledronic acid for preventing or delaying SREs in patients with bone metastases from solid tumours. Denosumab also has a comparable safety profile to bisphosphonates, with reduced risk of renal toxicity and acute phase reactions. Data from Europe suggest that denosumab is cost-effective for the prevention of SREs compared with zoledronic acid. Additionally, several new experimental bone-targeted agents show promise.

Conclusion

Recent progress may help to reshape evidence-based guidelines to improve patient care and reduce the economic burden of bone metastases.     

Zoledronic acid concurrent with either high- or reduced-dose palliative radiotherapy in the management of the breast cancer patients with bone metastases: a phase IV randomized clinical study

Introduction

In this prospective study, the efficacy and safety of radiotherapy combined with zoledronic acid was evaluated.

Materials and methods

Breast cancer patients with painful bone metastases were randomized to either high- or reduced-dose radiotherapy. All patients received zoledronic acid (4 mg) every 28 days from the beginning of radiotherapy. Analgesic and pain scores in addition to visual analog score (VAS) for treatment satisfaction and whole-body bone scintigraphy were evaluated.

Results and conclusion

No significant differences could be found in analgesic or pain scores and bone scintigraphy results between the groups. Our results suggest that reduced-dose radiotherapy produces similar response rates and response durations when used concomitantly with zoledronic acid.     

Randomized controlled trial of standardized education and telemonitoring for pain in outpatients with advanced solid tumors

Purpose

Previous studies have not defined the role of telemonitoring with educational tools in outpatients with advanced cancers. We tested the effectiveness of standardized education and telemonitoring for improving pain, distress, anxiety, depression, quality of life (QoL), and performance in outpatients with advanced cancers.

Methods

A total of 108 patients were randomly assigned to receive pain education alone (control arm) or pain education plus telemonitoring (experimental arm). Nursing specialists provided video-assisted educational material in both arms and daily telemonitoring for the first week in the experimental arm. Assessment was performed at baseline and 1 week and included evaluations of pain (Brief Pain Inventory, BPI), distress (Distress Thermometer, DT), anxiety, and depression (Hospital Anxiety and Depression Scale, HADS), QoL (QLQ-C30), and a Karnofsky score.

Results

Overall (n?=?108), pain intensity was significantly improved at 1 week, including worst pain (7.3 to 5.7, P?<?0.01) and average pain (4.6 to 3.8, P?<?0.01). Additionally, anxiety (HADS score?≥?11, 75 % to 56 %, P?<?0.01), depression (HADS score?≥?11, 73 % to 51 %, P?<?0.01), QoL (fatigue and insomnia), and the Karnofsky score (32 to 66, P?<?0.01) were also significantly improved at 1 week. However, the level of distress did not improve. The telemonitoring plus standardized education group showed more significant improvement in portion of pain >4 on VAS scale (35 % vs. 19 %, P?=?0.02).

Conclusions

Standardized pain education using nursing specialists is an efficient way to improve not only pain itself but also anxiety, depression, performance, and QoL. The addition of telemonitoring helps to improve pain management in the outpatient setting.     

A systematic review and meta-analysis on the use of traditional Chinese medicine compound kushen injection for bone cancer pain

Purpose

Bone cancer pain presents a clinical challenge with limitations of current treatments. Compound kushen injection (CKI) is a well-known traditional Chinese medicine (TCM) formulation in treatment of patients with bone cancer pain. The objective of this study is to assess the efficacy and safety of CKI for bone cancer pain.

Methods

A systematic literature search was conducted in nine databases until December 2012 to identify randomized controlled trials (RCTs) of CKI versus current western therapies for bone cancer pain. The primary outcome was total pain relief rate. The secondary outcomes were the quality of life and adverse events at the end of treatment course. The methodological quality of RCTs was assessed independently using six-item criteria according to the Cochrane Collaboration, and the level of evidence was assessed by the GRADE approach. All data were analyzed using Review Manager 5.1.0.

Results

Seven RCTs with 521 patients from 2010 to 2012 were identified. Compared with radiotherapy or bisphosphonates, seven RCTs showed significant effects of CKI for improving pain relief in patients with bone cancer pain (n?=?521, risk ratio (RR)?=?1.25, 95 % CI (95 % confidence intervals (CI)), 1.13 to 1.38, p?<?0.0001)), three RCTs for improving Karnofsky scoring (KPS) increase rate (n?=?305, RR?=?1.62, 95 % CI, 1.32 to 1.99, p?<?0.00001), 1 RCT for increasing KPS scores (n?=?78, mean difference (MD)?=?10.43, 95 % CI 4.76 to 16.10, p?=?0.0003). 4 RCTs reported adverse effects in both the treatment and control groups. The patients treated with CKI achieved statistically significant reductions of incidences of leukopenia (n?=?276, RR?=?0.32, 95 % CI, 0.21 to 0.47, p?<?0.00001) and nausea (n?=?78, RR?=?0.15, 95 % CI, 0.06 to 0.34, p?<?0.00001). No severe adverse events were found and no treatment was stopped because of adverse events of CKI in the treatment groups. However, the studies were deemed to have a high risk of bias.

Conclusion

This systematic review showed positive but weak evidence of CKI for bone cancer pain because of the poor methodological quality and the small quantity of the included trials. Future rigorously designed RCTs are required.     

Interpreting results from oncology clinical trials: a comparison of denosumab to zoledronic acid for the prevention of skeletal-related events in cancer patients

Background

Critically reviewing the design, endpoints, and results of clinical trials can be challenging to health care professionals. This paper will review the basic methods of presenting clinical outcomes in randomized trials and will focus on the number needed to treat (NNT) concept. NNT will then be applied to the case of bone-targeted therapies denosumab and zoledronic acid, which are used for the prevention of skeletal-related events (SREs) in a variety of disease sites.

Methods

A Medline search was performed to identify randomized trials comparing denosumab to zoledronic acid for the prevention of SREs in patients with advanced breast, prostate, and other cancer sites. The data were extracted, and point estimates for the primary and secondary trial endpoints were converted into the NNT parameter.

Results

NNT represents the number of patients that need to be treated with a new intervention in order to avoid one additional patient developing the event and is a powerful approach that can be used to make sense of numerical results from clinical trials. In patients with advanced breast, prostate, and other cancer sites, 18, 22, and 21 patients, respectively, would need to be treated with denosumab for at least 24?months to avoid one patient developing an SRE.

Conclusions

The NNT approach is a simple and effective method to express the findings of randomized trials in a clinically meaningful way. In this analysis, the incremental benefits of denosumab would be realized when a minimum of 18 to 22 patients are treated for a prolonged duration. Clinicians would have to weigh the costs and benefits between denosumab and zoledronic acid when bone-targeted therapy is indicated.     

Prevalence of anxiety and depression and their risk factors in Chinese cancer patients

Purpose

This paper aimed to obtain information on the levels of anxiety and depression among cancer patients in China. The factors influencing these psychological problems were also analyzed.

Methods

A total of 1,217 cancer patients were interviewed, and each participant was asked to complete a self-administered questionnaire. The anxiety status, depression status, disease stage, tumor site, pain status, and performance status of the patients during the week prior to the interview were assessed.

Results

The anxiety and depression prevalence rates were 6.49 and 66.72 %, respectively. The prevalence rates of depression were 60.62 % for head and neck cancer, 77.19 % for lung cancer, 57.9 % for breast cancer, 75.81 % for esophagus cancer, 63.40 % for stomach cancer, 68.42 % for liver cancer, 54.37 % for colorectal cancer, and 71.13 % for cervix cancer. The factors influencing depression of patients were performance status (P?<?0.0001), pain (P?=?0.0003), age (P?<?0.0001), and education level (P?<?0.0001). The risk factors of anxiety were performance status (P?=?0.0007), age (P?<?0.0001), and gender (P?<?0.0001).

Conclusions

Depression was a more important psychological problem than anxiety in cancer patients. Compared with 3.8 % of the prevalence of depression in normal population, depression level was high among Chinese cancer patients. Patients with lung, esophagus, and cervix cancers were the high-risk groups for depression. Poor performance status, pain, old age, and low-level education were the predicting factors for depression.     

An Observational Study of Concomitant Use of Emerging Therapies and Denosumab or Zoledronic Acid in Prostate Cancer

Purpose

This observational study of oncologic clinical practices was designed to describe real-world patterns of use of emerging therapies (abiraterone acetate, cabazitaxel, enzalutamide, radium-223, sipuleucel-T) in patients with castration-resistant prostate cancer and to characterize their concomitant use with denosumab or zoledronic acid.

Radiosynthesis of [124I]Iodometomidate and Biological Evaluation Using Small-Animal PET

Purpose

The application of radiolabelled inhibitors of cytochrome P450 enzymes is a novel approach for molecular imaging of adrenocortical masses to detect adrenal tumours. One potential tracer is radiolabelled iodometomidate (IMTO) with a common option for scintigraphic diagnosis and therapeutic applications. The aim of this study was to radiolabel iodometomidate with the positron-emitting radionuclide iodine-124 (¹²⁴I) for the investigation of the biological behaviour and pharmacokinetics with positron emission tomography (PET).

Procedures

[¹²⁴I]IMTO has been synthesized by oxidative radioiodo-destannylation, purified via semi-preparative HPLC and formulated in acetate-buffered saline, which contained ascorbic acid and ethanol to avoid radiolytic decomposition. Biological evaluation was performed in rats which received 5.5?±?0.7 MBq [¹²⁴I]IMTO in vivo. The radioactivity distribution (n?=?3) has been dynamically imaged from 0–120 min after intravenous (i.v.) injection by small-animal PET. Regions of interest have been defined manually in the reconstructed PET images, and the activity concentration was expressed as percent injected dose per gram tissue (%ID/g).

Results

[¹²⁴I]IMTO was prepared with a radiochemical yield of 83?±?5 % (n?=?3) and a radiochemical purity of >97 %. The final formulation of [¹²⁴I]IMTO was stable for up to 48 h at room temperature. Two hours after i.v. administration in rats, radioactivity concentration in the adrenal glands were 2.1?±?0.3 %ID/g, which was sufficient to achieve highest-contrast adrenal PET images.

Conclusions

In the present study, the biological characteristics of radioiodinated metomidate were evaluated. [¹²⁴I]IMTO appears as an attractive PET tracer for imaging of adrenals.     

Phase II study of glucosamine with chondroitin on aromatase inhibitor-associated joint symptoms in women with breast cancer

Purpose

Many women with hormone receptor-positive breast cancer discontinue effective aromatase inhibitor (AI) treatment due to joint symptoms.

Methods

We conducted a single-arm, open-label, phase II study evaluating glucosamine-sulfate (1,500 mg/day)?+?chondroitin-sulfate (1,200 mg/day) for 24 weeks to treat joint pain/stiffness in postmenopausal women with early stage breast cancer who developed moderate-to-severe joint pain after initiating AIs. The primary endpoint was improvement in pain/stiffness at week 24 assessed by the Outcome Measure in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) criteria. Secondary endpoints assessed changes in pain, stiffness, and function using the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index for hips/knees and the Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands (M-SACRAH) for hands/wrists. The Brief Pain Inventory (BPI) assessed pain interference, severity, and worst pain.

Results

Of 53 patients enrolled, 39 were evaluable at week 24. From baseline to week 24, 46 % of patients improved according to OMERACT-OARSI criteria. At week 24, there were improvements (all P?<?0.05) in pain and function as assessed by WOMAC and M-SACRAH, and in pain interference, severity, and worst pain as assessed by BPI. Estradiol levels did not change from baseline. The most commonly reported side effects were headache (28 %), dyspepsia (15 %), and nausea (17 %).

Conclusions

In this single-arm study, 24 weeks of glucosamine/chondroitin resulted in moderate improvements in AI-induced arthralgias, with minimal side effects, and no changes in estradiol levels. These results suggest a need to evaluate efficacy in a placebo-controlled trial.     

Prevalence of hepatic lesion types defined by T2-weighted and dynamic gadolinium-enhanced MR imaging in patients with metastasized neuroendocrine tumors

Purpose

Identifying liver metastases from neuroendocrine tumors (NETs) is a pretherapeutic challenge in patients who are candidates for liver resection. The aims of our study are to characterize and determine the frequency of different MRI characteristics of liver metastases caused by NETs in a lesion-by-lesion analysis and to determine the frequency of monomorphous and polymorphous metastases in a patient-by-patient analysis.

Methods

This retrospective study involved 47 patients with liver metastases arising from histologically confirmed NETs. In a lesion-by-lesion analysis, we classified these metastases according to their MRI characteristics as follows: hypervascular lesions with homogeneous or peripheral enhancement, hypovascular lesions, pure cystic lesions, and mixed solid/cystic lesions. In the patient-by-patient analysis, we distinguished patients whose metastases had the same MRI characteristics from patients with mixed lesion characteristics.

Results

A total of 376 metastases were analyzed. Of these, 84.3% (n = 317) were hypervascular, with 51.9% showing homogeneous enhancement and 32.4% (n = 122) showing peripheral enhancement. Another 7.4% (n = 28) were hypovascular, 5.3% (n = 20) were pure cystic, and 2.9% (n = 11) were mixed solid/cystic. After excluding three patients with solitary lesions, 40.9% of patients (n = 18) had mixed-type lesions, consisting of hypervascular lesions with either homogeneous or peripheral enhancement in 27.3% of cases (n = 12), while 59.1% of patients (n = 26) had identical lesions.

Conclusion

Approximately 15% of metastases have atypical MRI characteristics and are either hypovascular or cystic. Metastases with different MRI characteristics coexist in 40% of patients.

     

Quality of life outcomes in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: a controlled comparison

Purpose

Tyrosine kinase inhibitors (TKIs) are now standard treatment for chronic myeloid leukemia (CML). While TKIs have less toxicity than previous treatments, they have side effects that can impact quality of life (QOL).

Methods

This study compared CML patients taking a TKI for an average of 4.01 years (range 0.50–9.79 years) to age- and gender-matched controls with no history of cancer on measures of symptom burden, depression, fatigue, sleep, and health-related QOL.

Results

Compared to controls (n?=?62), CML patients (n?=?62) taking a TKI (imatinib 55 %, nilotinib 31 %, and dasatinib 14 %) reported significantly worse fatigue severity (p?<?.001), fatigue interference (p?<?.001), depression (p?=?.007), symptom burden (p?<?.001), and physical QOL (p?<?.001). TKI patients were also more likely meet established cutoffs for clinically meaningful fatigue (p values?<?.001) and depression (p?=?.004). There were no differences in mental QOL or sleep (p values?>?.010). Regarding specific symptoms, TKI patients were more likely to report nausea, diarrhea, itching, skin changes, swelling of arms or legs, and not looking like themselves (p values?<?.001).

Conclusions

These data suggest the need for interventions to address QOL in CML patients taking TKIs.     

Fast-track rehabilitation program and conventional care after esophagectomy: a retrospective controlled cohort study

Purpose

The purpose of this article is to evaluate fast-track rehabilitation program and conventional care after esophagectomy using a retrospective controlled cohort study in esophageal cancer patients.

Methods

Fifty-five patients underwent fast-track rehabilitation program and 57 patients underwent conventional care after esophagectomy. Fast-track rehabilitation program was performed to patients who have early movement, epidural analgesia control, fluid infusion volume control and enteral nutrition for early discharge. The other 57 patients underwent conventional care after esophagectomy. The average of hospital stay and complications were calculated in the patients between the two groups.

Results

The median length of hospital stay in the patients was significantly shorter after fast-track rehabilitation program than after conventional care (7.7 vs 14.8 day, P?<?0.01). The percentage of patients who developed complications was significantly lower 30 day after fast-track rehabilitation program than after conventional care (29.1 vs 47.4 %, P?<?0.05). 87.3 % in patients of the fast-track rehabilitation program group and 54.4 % in those of the conventional care group reported excellent to very good satisfaction with their pain control (P?=?0.000).

Conclusions

The fast-track rehabilitation program results in fewer complications, less postoperative pain, a reduction in the hospital length of stay, and quicker return to work and normal activities after esophagectomy.     

A prospective,open-label,multicenter study of the clinical efficacy of extended-release hydromorphone in treating cancer pain inadequately controlled by other analgesics

Purpose

The objective of this study was to evaluate whether extended-release hydromorphone (osmotic-controlled release oral delivery system [OROS] hydromorphone) treatment provided pain relief in cancer patients whose pain was inadequately controlled by other analgesics.

Methods

In this prospective, open-label, multicenter trial, patients who have sustained cancer pain with other analgesics were enrolled. After the baseline evaluation (visit 1), OROS hydromorphone was administered. Two evaluations (visits 2 and 3) were made: 29?±?7 and 57?±?7 days later, respectively. The primary end point was the pain intensity difference (PID) at visit 3 relative to visit 1 (expressed as percent PID).

Results

In total, 879 patients were screened and 432 completed all three visits. Of the 874 full analysis set patients, 343 (39.2 %) improved by more than 30 % PID. Of the 432 per-protocol patients, 282 (65.3 %) improved by more than 30 % PID. At visits 2 and 3, the degree of sleep disturbance, the number of awakenings, and the degree of sleep satisfaction were significantly better than at visit 1 (all P?<?0.0001 for both visit 1–visit 2 and visit 1–visit 3). However, this pain relief was not associated with improved quality of life (P?=?0.326 and P?=?0.055 for visit 1–visit 2 and visit 1–visit 3, respectively).

Conclusions

This study suggested that active pain management using the strong opioid OROS hydromorphone was beneficial in the management of cancer pain that was not controlled by other analgesics.     

Testing the ‘teachable moment’ premise: does physical activity increase in the early survivorship phase?

Purpose

Little is known about objectively measured physical activity during the early survivorship period. This study measured physical activity, fatigue, and quality of life (QOL) in breast cancer patients over the first year after completion of chemotherapy and compared results to a matched non-cancer group.

Methods

Data was obtained from 24 breast cancer subjects (mean ± SD) 50.9?±?12.8 years at time points of 6 weeks, 6 months and 1 year after completion of adjuvant chemotherapy and from 20 matched women. The following variables were assessed, physical activity (RT3 accelerometer and International Physical Activity Questionnaire), quality-of-life (EORTC QLQ C-30) and fatigue (Brief Fatigue Inventory).

Results

At 6 weeks after completion of chemotherapy, high levels of sedentary behaviour were found (6.8?±?1.9 h sedentary per day), which did not improve, and was no different to the comparison group (6.5?±?1.4 h). Less light activity was performed in the cancer cohort compared to the comparison group (p?=?0.003). Body mass index (BMI) increased significantly in the cancer cohort (p?=?0.015) and 1 year after chemotherapy finished only 13 % (n?=?3) had a BMI <25, while the comparable value was 45 % (n?=?9) in the non-cancer group. The QOL domain of cognitive function improved over the first 6 months (p?=?0.034) but physical functioning declined (p?=?0.008) over this time period. Fatigue did not change, and at the 1-year time point, 38 % of the cancer patients (n?=?11) reported high levels of fatigue.

Conclusion

This study highlighted the unchanging sedentary behaviour and weight gain of breast cancer survivors during the first year after completion of chemotherapy, which may inform rehabilitation models in this population.     

Important and relevant symptoms including pain concerns in hepatocellular carcinoma (HCC): a patient interview study

Purpose

We examined the health-related quality of life (HRQOL) and pain experiences of patients with hepatocellular carcinoma (HCC) and assessed content validity of existing patient-reported pain items for patients with HCC.

Methods

Semi-structured interviews to elicit symptoms, side effects and concerns were conducted with ten patients with HCC. Symptom and side effect importance was ranked on a 0 to 10 scale. Patients completed pain items from the Functional Assessment of Cancer Therapy—Hepatocellular (FACT-Hep) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire—Hepatocellular-18 (EORTC QLQ-HCC18).

Results

Mean age was 58 years (range 33–77). Spontaneously reported symptoms included fatigue (n?=?5), diarrhea (n?=?5), skin toxicities (n?=?5), and loss of appetite (n?=?4). Upon questioning, nine of ten patients reported experiencing pain over the course of their treatment. Over half of the importance rankings given for pain were 8 or higher on a 0 to 10 scale. Abdomen (n?=?7) and lower back (n?=?3) were the most common sites of pain. Pain onset varied from 6 months pre-diagnosis to over 2 years post-diagnosis. All patients indicated that FACT-Hep and EORTC items adequately assessed their pain.

Conclusions

Results support the content validity of FACT-Hep pain items for patients with HCC. The finding that patients typically did not spontaneously report pain but often ranked it as very important for their HRQOL upon questioning suggests a need for systematic, routine pain and other symptom assessment and management as an integral component of patient care in advanced HCC.     

Health-related quality of life and inflammatory markers in malignant pleural mesothelioma

Purpose

Malignant pleural mesothelioma (MPM) is a highly aggressive and symptomatic disease. We examined the relationship between health-related quality of life (HRQoL) and inflammatory markers, and the prognostic role of HRQoL in MPM patients.

Methods

MPM patients from two parallel phase II studies (thalidomide alone or thalidomide with chemotherapy) were included. HRQoL was assessed at baseline using the modified Lung Cancer Symptom Scale (LCSS). Baseline inflammatory markers and cytokines were measured. Spearman correlation was used to examine the relationship between inflammatory markers and HRQoL measures. The prognostic value of the HRQoL domains was examined using Cox proportional hazard model.

Results

Sixty-three patients were included: median age 61 years (range 44–79); 82 % male; 77 % Eastern Cooperative Oncology Group (ECOG) performance status 0–1; 44 % epithelial histology subtype. Baseline systemic symptoms of anorexia and fatigue, the summation symptoms of overall symptomatic distress, interference with normal activity and global QoL and the aggregate score of total LCSS score were all associated with elevated neutrophil-to-lymphocyte ratio, C-reactive protein and vascular endothelial growth factor levels at baseline (rho?≥?0.25; p?<?0.05). Baseline anorexia, fatigue, cough, dyspnoea, pain, overall symptomatic distress, interference with normal activity, global QoL and total LCSS score were all significantly related to survival (p?<?0.05) after adjusting for established prognostic factors (age, gender, histological subtype and performance status) and treatment effect.

Conclusions

In conclusion, HRQoL seems to relate to a patient's systemic inflammatory status and is associated with survival in MPM patients.     

Oral health conditions affect functional and social activities of terminally ill cancer patients

Purpose

Oral conditions are established complications in terminally ill cancer patients. Yet despite significant morbidity, the characteristics and impact of oral conditions in these patients are poorly documented. The study objective was to characterize oral conditions in terminally ill cancer patients to determine the presence, severity, and the functional and social impact of these oral conditions.

Methods

This was an observational clinical study including terminally ill cancer patients (2.5–3-week life expectancy). Data were obtained via the Oral Problems Scale (OPS) that measures the presence of subjective xerostomia, orofacial pain, taste change, and the functional/social impact of oral conditions and a demographic questionnaire. A standardized oral examination was used to assess objective salivary hypofunction, fungal infection, mucosal erythema, and ulceration. Regression analysis and t test investigated the associations between measures.

Results

Of 104 participants, most were ≥50 years of age, female, and high-school educated; 45 % were African American, 43 % Caucasian, and 37 % married. Oral conditions frequencies were: salivary hypofunction (98 %), mucosal erythema (50 %), ulceration (20 %), fungal infection (36 %), and other oral problems (46 %). Xerostomia, taste change, and orofacial pain all had significant functional impact; p?<?.001, p?=?.042 and p?<?.001, respectively. Orofacial pain also had a significant social impact (p?<?.001). Patients with oral ulcerations had significantly more orofacial pain with a social impact than patients without ulcers (p?=?.003). Erythema was significantly associated with fungal infection and with mucosal ulceration (p?<?.001).

Conclusions

Oral conditions significantly affect functional and social activities in terminally ill cancer patients. Identification and management of oral conditions in these patients should therefore be an important clinical consideration.