Quality of life improvement in patients with bone metastases undergoing palliative radiotherapy.

Background: The aim of the study was to analyze the impact of palliative radiotherapy on quality of life (QoL) in patients with symptomatic bone metastases. Materials and methods: We present the results from a prospective multicentric study including 128 patients who provided pre- and post-radiotherapy (one month after treatment) brief pain inventory (BPI) assessments. Worst pain was recorded using the BPI (range: 0-10). Pain response was described according to the International Bone Metastases Consensus on palliative radiation. Regarding QoL, for each pre- and post-radiation BPI-questionnaire, scores from the interference domains were summed and averaged to obtain an overall interference score. Results: There was a significant correlation between radiation treatment response and improvement in all functional interference domains except sleeping. Patients > 75 years old presented a significantly higher improvement in general activity, mood and relationships with others compared to patients ≤ 75 years old. Patients presenting a baseline pain score ≥ 8 showed a higher improvement in the general activity item (p = 0.049). There was no statistically significant association between pretreatment ECOG, chemotherapy, primary tumor location and radiation schedule with any of the functional interference items. Conclusions: Patients who report pain relief after palliative radiotherapy also present a better quality of life including physical and psychosocial aspects.

Pain response and quality of life assessment in patients with moderate/severe neuropathic pain due to bone metastasis undergoing treatment with palliative radiotherapy and tapentadol: A prospective multicentre pilot study.

INTRODUCTION: To assess pain response rate (RR) and quality of life (QoL), in patients with moderate/severe neuropathic pain (NP) due to bone metastasis (BM) undergoing palliative 3D radiotherapy plus tapentadol. METHODS: We conducted a prospective multicentre pilot study. Patients were assessed before radiotherapy using the validated questionnaire (Douleur Neuropathique en 4 questions). Response to radiotherapy (8 Gy-30 Gy/1-10fr) at one and two months was assessed according the International Bone Metastases Consensus criteria. INCLUSION CRITERIA: radiological evidence of BM, NP according to DN4 (cut-off score ≥ 4), no spinal cord compression, worst pain score ≥ 5/10. Nonparametric Mann-Whitney U test compared changes in QoL among response groups. RESULTS: Seventeen patients (13 men, 4 woman), median age 67 years (42-81), were included. Pre-treatment median pain severity was 7.5 (5-10). Median dose of tapentadol administered before radiotherapy was 100 mg/24 h (100-300 mg). Overall RR 1 month after radiotherapy was 10/16 = 62.5%: 3/16 (18.8%) achieving a complete response (CR) and 7/16 (43.8%) a partial response (PR). Overall RR 2 months after RT was 5/10 (50%): 10% a CR and 40% a PR. ITT RR for this study at 1 and 2 months was 10/17 = 59% and 5/17 = 29%, respectively. Patients responding to radiotherapy had significant improvement in EORTC QLQ-C30 emotional functioning (EF) (p = 0.025) and fatigue symptom scale scores (p = 0.035) one month after radiotherapy. Painful site symptom QLQ-BM22 scores improved 2 months after radiotherapy (p = 0.024). CONCLUSIONS: Palliative radiotherapy plus tapentadol shows an acceptable pain response and QoL improvement especially regarding EF, fatigue and painful site symptom scales in patients with moderate/severe NP due to BM. Therefore, it could be an alternative to manage NP in daily practice.

Intraoperative radiation therapy (IORT) for soft tissue sarcoma - ESTRO IORT Task Force/ACROP recommendations.

PURPOSE: To describe guidelines for the use of intraoperative radiation therapy (IORT) in the treatment of soft-tissue sarcomas (STS). METHODS: A panel of experts in the field performed a systematic literature review, supplemented their clinical experience and developed recommendations for the use of IORT in the treatment of STS. RESULTS: Based on the evidence from the systematic literature review and the clinical experience of the panel members, recommendations regarding patient selection, incorporation into multimodal treatment concepts and the IORT procedure itself are made. The rationale for IORT in extremity and retroperitoneal STS is summarized and results of the major series in terms of patient and treatment characteristics, oncological outcome and toxicity are presented. We define surgical factors, volumes for irradiation, technical requirements, dose prescription, recording and reporting, treatment delivery and care during the course of IORT covering the main IORT techniques used for the treatment of STS. In extremity STS, evidence originates from a few small prospective and mainly from retrospective single centre studies. Based on those reports, IORT containing-approaches result in very high local control rates with low rates of acute and late toxicity. In retroperitoneal sarcomas, evidence is derived from one prospective randomized trial, a few prospective and a large number of retrospective studies. The randomized trial compared IORT combined with moderate doses of postoperative external-beam radiation therapy (EBRT) to high-dose postoperative EBRT alone after gross total resection, clearly favouring the IORT-containing approach. These results have been confirmed by the prospective and retrospective studies, which similarly showed high local control rates with acceptable toxicity, mainly favouring combinations of preoperative EBRT and IORT. CONCLUSIONS: IORT-containing approaches result in high rates of local control with low to acceptable toxicity rates. Based on the available evidence, we made recommendations for the use of IORT in STS. Clinicians and researchers are encouraged to use these guidelines in clinical routine as well as in the design of future trials.

Analysis of predictors of pain response in patients with bone metastasis undergoing palliative radiotherapy: Does age matter?

INTRODUCTION: To evaluate whether age is a predictor of pain response after radiotherapy for painful bone metastasis (BM). METHODS: Between June 2010 and June 2014, 204 patients with BM undergoing palliative radiotherapy participated in a multicentre prospective study. Patients completed the Brief Pain Inventory (BPI) to rate the intensity pain (from 0 to 10) at baseline and 4 weeks after radiotherapy. To determine which variables predicted pain response and particularly whether age is a predictor, logistic regression analysis was used. Baseline variables considered were: age (≤65/66-75/>75 years), sex, Eastern Cooperative Oncology Group performance status (0-1/≥2), pretreatment pain score (≤4/5-7/≥8), radiotherapy (single/multiple fraction), primary tumour location, visceral metastases (yes/no), concomitant systemic chemotherapy and bisphosphonate use (yes/no). RESULTS: Pain response was assessed in the 128 patients who completed BPI pretreatment and at 4 weeks after radiotherapy. According to univariate analysis, pain response was better in over 75-year-olds than younger patients: (OR, 3.2; 95% CI, 1.1-9.1; P = 0.031). Response was better in patients receiving multiple fractions rather than a single fraction of 8 Gy (OR, 2.8; 95% CI, 1.2-6.1; P = 0.01), and in patients with a pretreatment pain score ≥8 vs ≤7 (OR, 2.4; 95% CI, 1.1-5.0; P = 0.017). No other variables were significant. Multivariate analysis showed that treatment schedule (OR, 3.4; 95% CI 1.4-7.9; P = 0.004) and pre-radiotherapy pain score (OR, 2.8; 95% CI 1.3-6.3; P = 0.009) were the only independent predictors of pain response. CONCLUSION: All patients with painful bone metastasis should be referred for palliative radiotherapy to relieve the pain regardless of age. Therefore, an older age should not be a reason to withhold palliative radiation treatment.

Incidence of pain flare following palliative radiotherapy for symptomatic bone metastases: multicenter prospective observational study.

BACKGROUND: Palliative radiotherapy (RT) is an effective treatment for symptomatic bone metastases. Pain flare, a transient worsening of the bone pain after RT, has been described in previous reports with different incidence rates. The aim of the study was to prospectively evaluate the incidence of pain flare following RT for painful bone metastases and evaluate its effects on pain control and functionality of the patients. METHODS: Between June 2010 and June 2014, 204 patients were enrolled in this study and 135 patients with complete data were evaluable. Pain flare was defined as a 2- point increase in worst pain score as compared with baseline with no decrease in analgesic intake or a 25% increase in analgesic intake as compared with baseline with no decrease in worst pain score. All pain medications and worst pain scores were collected before, daily during, and for 10 days after RT. The Brief Pain Inventory (BPI) was filled out on the pretreatment and at the 4 weeks follow-up visit. RESULTS: There were 90 men (66.7%) and 45 women (33.3%). Mean age was 66 years (SD 9.8). The most common primary cancer site was lung in 42 patients (31.1%), followed by prostate in 27 patients (20.0%). Forty-two patients (31.1%) patients received a single fraction of 8 Gy and 83 (61.5%) received 20 Gy in five fractions. The overall pain flare incidence across all centers was 51/135 (37.7%). The majority of pain flares occurred on days 1-5 (88.2%). The mean duration of the pain flare was 3 days (SD: 3). There were no significant relationships between the occurrence of pain flare and collected variables. All BPI items measured four weeks after end of RT showed significant improvement as compared with pretreatment scores (p < 0.001). No significant differences in BPI time trends were found between patients with and without flare pain. CONCLUSION: Pain flare is a common event, occurring in nearly 40% of the patients that receive palliative RT for symptomatic bone metastases. This phenomenon is not a predictor for pain response.

Interval between neoadjuvant treatment and definitive surgery in locally advanced rectal cancer: impact on response and oncologic outcomes.

PURPOSE: The optimal waiting period between neoadjuvant treatment completion and surgery in locally advanced rectal cancer (LARC) is controversial. The specific purpose of this study was to evaluate the effect of prolonging this interval on the pathologic response, postoperative morbidity, and long-term oncologic outcomes. METHODS: Retrospective data analysis is reported from LARC patients who had been treated with chemoradiation followed by surgery and intra-operative radiotherapy, between February 1995 and December 2012. In total, two groups were studied, according to the time elapsed between neoadjuvant treatment and surgery: conventional interval (CI; <6 weeks) and delayed interval (DI; ≥6 weeks). Clinicopathological data related to tumor response, postoperative morbidity, and oncologic outcomes were compared. RESULTS: This study included 335 consecutive LARC patients. There was a higher proportion of patients with clinical staging nodal involvement (cN+) in the DI group (76.6 vs. 64.1 %; p = 0.01). The pathologic complete response (pCR) was not significantly different among groups (8.8 vs. 12.1 %; p = 0.34). Longer intervals did not affect complication incidence or severity or hospital admission length. Certain postneoadjuvant tumor effect parameters were significantly increased in the DI group, including N-downstaging and T-downsizing. After a median follow-up of 71 months, patients in the DI group presented with superior 5-year overall survival (OS) (55.9 vs. 70.4 %, p = 0.014); however, no statistically significant differences were observed in 5-year disease-free survival (DFS) or 5-year local control (LC) (69.9 vs. 74.9 %, p = 0.223; 90.4 vs. 94.5 %, p = 0.123, respectively). CONCLUSIONS: A modest surgical interval delay (≥6 weeks) did not increase postoperative complications and was identified as a favorable prognostic factor for OS, although no differences were observed in pCR, LC, or DFS. Innovative multidisciplinary strategies incorporating further time extension of the surgical interval can be safely explored.

Post hoc analysis of pregabalin vs. non-pregabalin treatment in patients with cancer-related neuropathic pain: better pain relief, sleep and physical health.

BACKGROUND AND PURPOSE: A previous study of cancer-related neuropathic pain (NP) found that a 10-fold increase in pregabalin (PGB) use increased patients' satisfaction with treatment. Further research of PGB vs. non-pregabalin (non-PGB) treatment was carried out to assess if the use of more specific NP-targeting drugs, such as PGB, in combined therapy, in patients with cancer-related NP, provides better health outcomes. PATIENTS AND METHODS: Post hoc analysis of PGB- vs. non- PGB-treated patients in a 2-month epidemiological, prospective, multicentre study to assess NP prevalence and management in cancer pain patients visiting radiotherapy oncologic units. Patients undertook the Brief Pain Inventory (BPI), Hospital Anxiety and Depression Scale (HADS), the Medical Outcomes Sleep Scale (MOS-Sleep) and the short form (SF-12) Health Survey. RESULTS: A total of 273 patients with no previous PGB treatment: 162 were treated with PGB polytherapy and 111 with other treatments. At 8 weeks, satisfaction with treatment was 92.6% (PGB) vs. 78.9% (non-PGB), p=0.0024, and benzodiazepine use 37.8% (non-PGB) vs. 19.8% (PGB), p=0.0009. The decreases in BPI total pain intensity and total interference with activities and in MOS overall sleep problems index were significantly larger in the PGB group. CONCLUSIONS: The addition of more specific NP-targeting drugs to usual treatment, such as PGB, in NP cancer patients provides more satisfaction with treatment and better outcomes in terms of pain intensity, interference with activities and sleep than treatments without specific NP-targeting drugs. Anxiolytic profile of PGB could allow for less use of benzodiazepines.