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A prospective Phase II study for the efficacy of radiotherapy in combination with zoledronic acid in treating painful bone metastases from gastrointestinal cancers.

ABSTRACT: We investigated the efficacy of combined radiotherapy (RT) and zoledronic acid in treating painful bone metastases from gastrointestinal cancers. Sixty patients were prospectively enrolled between November 2014 and July 2016. The most common primary cancer type was hepatocellular carcinoma (HCC, n = 25), followed by colorectal cancer (n = 6). Patients received external beam RT of 30-54 Gy in 10-17 fractions or 20 Gy in 5 fractions for symptomatic bone metastases. On the first day of RT, patients received 4 mg intravenous zoledronic acid, which was repeated monthly for a total of six cycles. The mean pain score before treatment was 6.7, and it decreased to 2.8 at 1 month and 2.1 at 3 months (P < 0.001).The overall pain response rates at 1 and 3 months were 95% and 96%, respectively. Among the 24 patients who underwent magnetic resonance imaging, 71% were responders, with a complete response in 1 patient and partial in 16 patients. Combined treatment significantly decreased levels of macrophage inflammatory protein-1? and matrix metalloproteinase (MMP)-2 and -3 compared with baseline (all P < 0.05). In HCC patients, IL-6 and MMP-9 levels were significantly lower 1 month after treatment (P < 0.05). The mean quality of life (QOL) score improved from 66 to 56 at 1 month (P < 0.001) and 55 at 3 months (P = 0.016). The median survival was 7 months. In conclusion, RT with zoledronic acid decreased bone pain and improved QOL in patients with painful bone metastases from gastrointestinal cancers. Radiographic findings and serum biomarker measurements were closely correlated with therapeutic responses.

SUBMITTER: Choi J

PROVIDER: S-EPMC6430247 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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A prospective Phase II study for the efficacy of radiotherapy in combination with zoledronic acid in treating painful bone metastases from gastrointestinal cancers.

Choi Jinhyun J Lee Eun Jung EJ Yang Seung Hyun SH Im Yoo Ri YR Seong Jinsil J

Journal of radiation research 20190301 2

We investigated the efficacy of combined radiotherapy (RT) and zoledronic acid in treating painful bone metastases from gastrointestinal cancers. Sixty patients were prospectively enrolled between November 2014 and July 2016. The most common primary cancer type was hepatocellular carcinoma (HCC, n = 25), followed by colorectal cancer (n = 6). Patients received external beam RT of 30-54 Gy in 10-17 fractions or 20 Gy in 5 fractions for symptomatic bone metastases. On the first day of RT, patients ...[more]

PMID: 30445597

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Project description:ImportanceMany studies that found improved quality of life (QOL) after radiotherapy of bone metastases have small sample sizes and do not use specific questionnaires. How soon after radiotherapy one can expect an improvement in QOL is unknown.ObjectiveTo investigate QOL at days 10 and 42 after radiotherapy with a bone metastases-specific QOL tool.Design, setting, and participantsIn this secondary analysis of the NCIC Clinical Trials Group Symptom Control Trial SC.23, a double-blind randomized clinical trial that investigated dexamethasone for the prophylaxis of pain flare after radiotherapy, patients were accrued from 23 Canadian centers from May 30, 2011, to December 11, 2014, and were followed up for 42 days after treatment. Participants referred for radiotherapy for bone metastases were required to have a pain score at the site(s) of treatment of at least 2 (range, 0-10).InterventionsPatients were treated with a single 8-Gy radiotherapy dose for 1 or 2 bone metastases.Main outcomes and measuresPatients reported their worst pain score and analgesic intake at baseline and days 10 and 42 after treatment. Pain response was assessed with International Bone Metastases Consensus Endpoint Definitions. Self-reported QOL was completed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Bone Metastases Module (QLQ-BM22) and the European Organisation for Research and Treatment of Cancer Quality of Life Core 15 Palliative (QLQ-C15-PAL) at the same time points.ResultsA total of 298 patients were accrued (median age, 68.8 [range, 32-94] years at day 10 and 68.0 [range, 34-90] years at day 42). A total of 122 patients (40.9%) responded to radiotherapy at day 10 and 116 patients (38.9%) at day 42. At day 10, compared with nonresponders, patients with a pain response had a greater reduction in pain (mean reduction, 17.0 vs 1.8; P = .002) and pain characteristics (mean reduction, 12.8 vs 1.1; P = .002), as well as greater improvements in functional interference (mean increase, 11.6 vs 3.6; P = .01) and psychosocial aspects (mean increase, 1.2 points in responders vs mean decrease of 2.2 points in nonresponders, P = .04). Comparing changes in QOL from baseline to day 42, responders had significantly greater improvements in the physical (mean increase, 6.2 vs -9.0; P < .001), emotional (mean increase, 12.3 vs -5.5; P < .001), and global domains (mean increase, 10.3 vs -4.5; P < .001) of the QLQ-C15-PAL compared with nonresponders.Conclusions and relevanceForty percent of patients experienced pain reduction and better QOL at day 10 after radiotherapy with further improvements in QOL at day 42 in responders. A single 8-Gy radiotherapy dose for bone metastases should be offered to all patients, even those with poor survival.Trial registrationclinicaltrials.gov Identifier: NCT01248585.

Project description:BackgroundRadiotherapy has a good effect in palliation of painful bone metastases, with a pain response rate of more than 60%. However, shortly after treatment, in approximately 40% of patients a temporary pain flare occurs, which is defined as a two-point increase of the worst pain score on an 11-point rating scale compared to baseline, without a decrease in analgesic intake, or a 25% increase in analgesic intake without a decrease in worst pain score, compared to baseline. A pain flare has a negative impact on daily functioning and mood of patients. It is thought to be caused by periostial edema after radiotherapy. Dexamethasone might diminish this edema and thereby reduce the incidence of pain flare. Two non-randomized studies suggest that dexamethasone reduces the incidence of a pain flare by 50%. The aim of this trial is to study the effectiveness of dexamethasone to prevent a pain flare after palliative radiotherapy for painful bone metastases and to determine the optimal dose schedule.Methods and designThis study is a three-armed, double-blind, placebo-controlled multicenter trial. We aim to include 411 patients with uncomplicated painful bone metastases from any type of primary solid tumor who receive short schedule radiotherapy (all conventional treatment schedules from one to six fractions). Arm 1 consists of daily placebo for four days, arm 2 starts with 8 mg dexamethasone before the (first) radiotherapy and three days placebo thereafter. Arm 3 consists of four days 8 mg dexamethasone. The primary endpoint is the occurrence of a pain flare. Secondary endpoints are pain, quality of life and side-effects of dexamethasone versus placebo. Patients complete a questionnaire (Brief Pain Inventory with two added questions about side-effects of medication, the EORTC QLQ-C15-PAL and QLQ-BM22 for quality of life) at baseline, daily for two weeks and lastly at four weeks.DiscussionThis study will show whether dexamethasone is effective in preventing a pain flare after palliative radiotherapy for painful bone metastases and, if so, to determine the optimal dose.Trial registrationThis study is registered at ClinicalTrials.gov: NCT01669499.

Project description:BackgroundIn preclinical studies, FLASH therapy, in which radiation delivered at ultrahigh dose rates of ≥40 Gy per second, has been shown to cause less injury to normal tissues than radiotherapy delivered at conventional dose rates. This paper describes the protocol for the first-in-human clinical investigation of proton FLASH therapy.ObjectiveFAST-01 is a prospective, single-center trial designed to assess the workflow feasibility, toxicity, and efficacy of FLASH therapy for the treatment of painful bone metastases in the extremities.MethodsFollowing informed consent, 10 subjects aged ≥18 years with up to 3 painful bone metastases in the extremities (excluding the feet, hands, and wrists) will be enrolled. A treatment field selected from a predefined library of plans with fixed field sizes (from 7.5 cm × 7.5 cm up to 7.5 cm × 20 cm) will be used for treatment. Subjects will receive 8 Gy of radiation in a single fraction-a well-established palliative regimen evaluated in prior investigations using conventional dose rate photon radiotherapy. A FLASH-enabled Varian ProBeam proton therapy unit will be used to deliver treatment to the target volume at a dose rate of ≥40 Gy per second, using the plateau (transmission) portion of the proton beam. After treatment, subjects will be assessed for pain response as well as any adverse effects of FLASH radiation. The primary end points include assessing the workflow feasibility and toxicity of FLASH treatment. The secondary end point is pain response at the treated site(s), as measured by patient-reported pain scores, the use of pain medication, and any flare in bone pain after treatment. The results will be compared to those reported historically for conventional dose rate photon radiotherapy, using the same radiation dose and fractionation.ResultsFAST-01 opened to enrollment on November 3, 2020. Initial results are expected to be published in 2022.ConclusionsThe results of this investigation will contribute to further developing and optimizing the FLASH-enabled ProBeam proton therapy system workflow. The pain response and toxicity data acquired in our study will provide a greater understanding of FLASH treatment effects on tumor responses and normal tissue toxicities, and they will inform future FLASH trial designs.Trial registration: ClinicalTrials.gov NCT04592887; http://clinicaltrials.gov/ct2/show/NCT04592887.International registered report identifier (irrid)DERR1-10.2196/41812.

Project description:BackgroundThe spine is the most frequent location of bone metastases. Local treatment aims at palliation of pain and, given the increased likelihood of long-term cancer survival, at local control. Kyphoplasty and intraoperative radiotherapy (Kypho-IORT) provided instantaneous pain relief in 70% of patients at the first day after the intervention and resulted in local control rates of > 93% at 1 year in a recently conducted phase I/II trial. To assess its clinical value, we designed a phase III trial which tests Kypho-IORT against the most widespread standard-of-care, external beam radiotherapy (EBRT), in patients with painful vertebral metastases.MethodsThis phase III study includes patients ≥50 years of age with up to 4 vertebral metastases and a pain score of at least 3/10 points on the visual/numeric analogy scale (VAS). Patients randomized into the experimental arm (A) will undergo Kypho-IORT (Kyphoplasty plus IORT with 8 Gy prescribed to 13 mm depth). Patients randomized into the control arm (B) will receive EBRT with either 30 Gy in 10 fractions or 8 Gy as a single dose. The primary end point is pain reduction defined as at least - 3 points on the VAS compared to baseline at day 1. Assuming that 40% of patients in the Kypho-IORT arm and 5% of patients in the control arm will achieve this reduction and 20% will drop out, a total of 54 patients will have to be included to reach a power of 0.817 with a two-sided alpha of 0.05. Secondary endpoints are evaluation of the percentage of patients with a pain reduction of at least 3 points at 2 and 6 weeks, local tumor control, frequency of re-intervention, secondary fractures/sintering, complication rates, skin toxicity/wound healing, progression-free survival (PFS), overall survival (OS) and quality of life.DiscussionThis trial will generate level 1 evidence on the clinical value of a one-stop procedure which may provide instantaneous pain relief, long-term control and shortened intervals to further adjuvant (systemic) therapies in patients with spinal metastases.Trial registrationRegistered with ClinicalTrials.gov, number: NCT02773966 (Registration date: 05/16/2016).

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A prospective Phase II study for the efficacy of radiotherapy in combination with zoledronic acid in treating painful bone metastases from gastrointestinal cancers.

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A prospective Phase II study for the efficacy of radiotherapy in combination with zoledronic acid in treating painful bone metastases from gastrointestinal cancers.

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