放射加博宁治疗骨转移癌的病例分析

目的:观察放疗和博宁对骨转移癌的止痛效果。方法:对100例骨转移癌患者进行回顾性分析,单纯放疗30例,博宁加放疗14例,博宁加放化疗56例。结果:全组总有效率为89%,显效率达51%。各组有效率:单放组为83-3%,博宁加放疗组为92.9%,博宁加放化组为91.1%。三组间止痛效果无显著性差异(P>0.05)。在应用博宁治疗组中有一例出现类似过敏反应症状,其他无明显毒副反应发生。结论:放射治疗骨转移癌止痛迅速而有效。博宁治疗骨转移癌止痛效果明显,尤其适合应用于多发性骨转移癌患者。二者联合应用效果更加。     

唑来膦酸延缓骨转移癌放射治疗的临床研究

目的以帕米膦酸二钠为对照,研究唑来膦酸对延缓骨转移癌放射治疗事件发生的临床疗效。方法对118例骨转移癌患者,随机分为病例组60例,对照组58例,以疼痛持续加重,X线或CT证实骨转移病灶进展或有可能导致病理性骨折而行放射治疗为观察终点,研究唑来膦酸延缓骨转移癌放射治疗事件出现时间的临床疗效。结果近期止痛有效率和获益率在唑来膦酸组分别为55.36%,65.18%;帕米膦酸组为35.19%,44.44%,P<0.05;放疗事件发生率在唑来膦酸组为34.21%,帕米膦酸钠组为54.28%,P>0.05;发生放疗事件中位时间在唑来膦酸组为121天,帕米膦酸钠组为189天,P=0.041。结论唑来膦酸近期止痛的临床有效率、获益率和总体骨相关事件(SRE)危险性降低的比例均高于帕米膦酸二钠。     

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

BackgroundThe 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 methodsWe 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.ResultsThere 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.ConclusionsPatients who report pain relief after palliative radiotherapy also present a better quality of life including physical and psychosocial aspects.     

Radiation therapy in the last month of life

Aim

We sought to survey a large, multi-center patient sample to better characterize/quantify RT utilization at the end of life.

Background

Few objective data exist for radiation therapy (RT) delivery at end of life (EOL).

Materials and methods

Data were retrieved for all patients receiving RT in calendar year 2010 in the Department of Radiation Oncology at Indiana University (IU) and Howard University (HU) hospitals. Specific attention was made of the group of patients receiving RT in the last 30 days of life.

Results

A total of 852 patients received all or part of their RT during 2010 (HU: 139, IU: 713). At time of analysis in early 2012, 179 patients had died (21%). Fifty-four patients (6.3% of total; 30% of expired patients) died within 30 days of receiving their last treatment. Twenty patients (2.3% of total; 11.2% of expired patients) received RT within their last week of life. For both sites, the median time until death from completion of therapy was 12.5 days (range 2–30 days).

Conclusions

Radiation in the last month of life is likely to provide minimal palliation or survival benefit. This, coupled with the financial implications, time investment, and physical costs, suggests that physicians and patients should more strongly consider hospice, and minimize duration of palliative RT courses as far as possible. As with chemotherapy, RT utilization at EOL should be considered for collection as an overuse metric.     

Incidence of bone metastases and survival after a diagnosis of bone metastases in breast cancer patients

Background: Bone is the most common metastatic site associated with breast cancer. Using a database of women with breast cancer treated at Guy's Hospital, London 1976–2006 and followed until end 2010, we determined incidence of and survival after bone metastases. Methods: We calculated cumulative incidence of bone metastases considering death without prior bone metastases as a competing risk. Risk of bone metastases was modelled through Cox-regression. Survival after bone metastases diagnosis was calculated using Kaplan–Meier methodology. Results: Of the 7064 women, 589 (22%) developed bone metastases during 8.4 years (mean). Incidence of bone metastases was significantly higher in younger women, tumour size >5 cm, higher tumour grade, lobular carcinoma and ≥four positive nodes, but was not affected by hormone receptor status. Median survival after bone metastases diagnosis was 2.3 years in women with bone-only metastases compared with <1 year in women with visceral and bone metastases. There was a trend for decreased survival for patients who developed visceral metastases early, and proportionately fewer patients in this group. Interpretation: Incidence of bone metastases has decreased but bone metastases remain a highly relevant clinical problem due to the large number of patients being diagnosed with breast cancer.     

Radiation therapy for bone-only metastases in breast cancer patients: A GOCO survey of current clinical practice

IntroductionThe role of radiation therapy (RT) for patients with bone-only metastatic (BOM) breast cancer has not been investigated sufficiently. The aim of this survey was to evaluate current clinical practice in treating breast cancer patients with BOM in Radiation Therapy Departments in Catalonia and Occitania within the scope of the GOCO group.Materials and methodsAn electronic questionnaire was completed by experienced radiation oncologists from fourteen RT centers. The items surveyed the professional experience, therapeutic approach, technique, dose stereotactic body RT (SBRT) availability.ResultsAll Radiation Oncology Departments (ROD) in Catalonia (12) and Occitania (2) responded to the survey. Eleven (78.5%) of the RODs advise RT for BOM as initial treatment in the oligometastatic setting. RT to asymptomatic bone oligometastases is more often restricted for “risky lesions”. The most inconsistent approaches were the treatment for asymptomatic lesions, when to treat bone metastases with respect to systemic treatment (ST) and the indication for RT after a complete response to ST.ConclusionWhile BOM breast cancer patients have a relatively good prognosis, there is a lack of consistency in their approach with RT. This can be explained by the absence of evidence-based guidelines and an incomplete availability of SBRT.     

Hippocampal dose during Linac-based stereotactic radiotherapy for brain metastases: An observational study

IntroductionAim of the present study is to evaluate homolateral and contralateral hippocampus (H-H, C-H, respectively) dose during Fractionated Stereotactic Radiotherapy (FSRT) or Radiosurgery (SRS) for brain metastases (BM).Materials & methodsPatients with BM < 5, size ≤ 30 mm, KPS ≥ 80 and a life expectancy > 3 months, were considered for SRS/FSRT (total dose 15–30 Gy, 1–5 fractions). For each BM, a Flattening Filter Free (FFF) Volumetric Modulated Arc Therapy (VMAT) plan was generated with one or two arcs. Hippocampi were not considered during optimizations phase and were contoured and evaluated retrospectively in terms of dose: the Dmedian, Dmean, D0.1cc and the V1Gy, V2Gy, V5Gy and V10Gy were analyzed.ResultsFrom April 2014 to December 2015, 81 BM were treated with FFF-FSRT/SRS. For the H-H, the average values of Dmedian, Dmean and D0.1cc were 1.5Gy, 1.54Gy and 2.2Gy, respectively, while the V1Gy, V2Gy, V5Gy and V10Gy values were 25%, 8.9%, 8.9% and 2.1%, respectively. For the C–H, the average Dmedian, Dmean and D0.1 cc were 0.7Gy, 0.7Gy, 0.9Gy, respectively, while the average values of V1Gy, V2Gy, V5Gy and V10Gy were 18%, 10.2%, 2.8% and 1.4%, respectively. Tumor dimension, tumor cranial-caudal length and the distance between BM and H-H were correlated to Dmedian, Dmean and D0.1cc. For C-H, only the distance from PTV was correlated with a dose reduction.ConclusionDuring FFF-FSRT/SRS, hippocampus received a negligible dose. Despite its clinical significance is still under evaluation, in patients with a long life expectancy, H-H should be considered during Linac-based FSRT/SRS.     

Stereotactic body radiation therapy for liver metastases: Clinical outcomes and literature review

Background and aimThe role of stereotactic body radiation therapy (SBRT) in the management of liver metastasis is increasing, using ablative doses with the goal of local control and ultimately improving survival. The aim of this study is to evaluate our initial results regarding local control, overall survival and toxicity in patients with liver metastases treated with this technique, due to the lack of evidence reported in Latin America.Materials/methodsWe performed a retrospective chart review from November 2012 to June 2018 of 24 patients with 32 liver metastases. Kaplan–Meier curves were constructed for local control and overall survival. Clinical and prognostic factors were further analyzed by independent analysis. Median follow-up period was 22 months (range, 1–65 months).ResultsMedian age was 62 years (range, 40–84 years). Colorectal carcinoma was the most common primary cancer. Overall 1-year and 2-years local control rates were 82% (95% Confidence Interval [CI], 70–98%) and 76.2% (95% CI, 45–90%), respectively. Median overall survival rate was 35 months (95%, CI 20.5–48 months). Overall 1-year and 2-year survival rates were 85.83% (95% CI, 64–99%) and 68% (95% CI, 45–84%), respectively. No acute or late grade 3 or 4 toxicity was observed during the follow-up period.ConclusionsSBRT achieves excellent local control and overall survival rates with low toxicity in patients with liver metastases. Based on our literature review, our results are consistent with larger reports. Further randomized trials are required to compare with other local therapies.     

The Italian multicentre dosimetric study for lesion dosimetry in 223Ra therapy of bone metastases: Calibration protocol of gamma cameras and patient eligibility criteria

PurposeThe aims of this work were to explore patient eligibility criteria for dosimetric studies in ²²³Ra therapy and evaluate the effects of differences in gamma camera calibration procedures into activity quantification.MethodsCalibrations with ²²³Ra were performed with four gamma cameras (3/8-inch crystal) acquiring planar static images with double-peak (82 and 154 keV, 20% wide) and MEGP collimator. The sensitivity was measured in air by varying activity, source-detector distance, and source diameter. Transmission curves were measured for attenuation/scatter correction with the pseudo-extrapolation number method, varying the experimental setup. ²²³Ra images of twenty-five patients (69 lesions) were acquired to study the lesions visibility. Univariate ROC analysis was performed considering visible/non visible lesions on ²²³Ra images as true positive/true negative group, and using as score value the lesion/soft tissue contrast ratio (CR) derived from ^99mTc-MDP WB scan.ResultsSensitivity was nearly constant varying activity and distance (maximum s.d. = 2%). Partial volume effects were negligible for object area ⩾960 mm². Transmission curve measurements are affected by experimental setup and source size, leading to activity quantification errors up to 20%. The ROC analysis yielded an AUC of 0.972 and an optimal threshold of CR of 10, corresponding to an accuracy of 92%.ConclusionThe minimum calibration protocol requires sensitivity and transmission curve measurements varying the object size, performing a careful procedure standardisation. Lesions with ^99mTc-MDP CR higher than 10, not overlapping the GI tract, are generally visible on ²²³Ra images acquired at 24 h after the administration, and possibly eligible for dosimetric studies.     

Skeletal metastases: decreasing tumor burden by targeting the bone microenvironment

Several common cancers often metastasize to the skeleton in advanced disease. Bone metastases are incurable and cause protracted, severe symptoms. Growth of tumor in bone is driven by a vicious cycle: tumor-secreted factors stimulate bone cells, which in turn release growth factors and cytokines. The bone-derived factors fuel the vicious cycle by acting back on the tumor cells. The vicious cycle offers novel targets for the treatment of advanced cancers. Treatments can inhibit bone cells (osteoclasts and osteoblasts) that are stimulated by tumor-secreted factors. Drugs can also inhibit tumor responses to factors enriched in the bone microenvironment, such as transforming growth factor-beta. Animal models show that these approaches, especially combination treatments, can reduce tumor burden. The results suggest a novel paradigm in which tumor growth can be effectively inhibited by drugs that target cells in the bone microenvironment and not the tumor cells themselves.     

Stereotactic ablative radiation therapy for spinal metastases: experience at a single Brazilian institution

BackgroundThis study aims to assess the clinical outcomes of patients with spine metastases who underwent stereotactic ablative radiation therapy (SABR) as part of their treatment. SABR has arisen as a contemporary treatment option for spinal metastasis patients with good prognoses.Materials and methodsBetween November 2010 and September 2018, Spinal SABR was performed in patients with metastatic disease in different settings: radical (SABR only), postoperative (after decompression and/or fixation surgery), and reirradiation. Local control (LC), pain control, overall survival (OS) and toxicities were reported.ResultsEighty-five patients (corresponding to 96 treatments) with spine metastases were included. The median age was 59 years (range, 23–91). In most SA BR (82.3%, n = 79) was performed as the first local spine treatment, while in 12 settings (12.5%), fixation and/or decompression surgery was performed prior to SABR. Two-year overall survival rate was 74.1%, and median survival was 19 months. The LC rate at 2 years was 72.3%. With regard to pain control, among 67 patients presenting with pain before SA BR, 83.3% had a complete response, 12.1% had a partial response, and 4.6% had progression. Vertebral compression fractures occurred in 10 patients (11.7%), of which 5 cases occurred in the reirradiation setting. Radiculopathy and myelopathy were not observed. No grade III or IV toxicities were seen.ConclusionThis is the first study presenting a Brazilian experience with spinal SA BR, and the results confirm its feasibility and safety. SABR was shown to produce good local and pain control rates with low rates of adverse events.     

Massage therapy for osteoarthritis of the knee: a randomized dose-finding trial

Background

In a previous trial of massage for osteoarthritis (OA) of the knee, we demonstrated feasibility, safety and possible efficacy, with benefits that persisted at least 8 weeks beyond treatment termination.

Methods

We performed a RCT to identify the optimal dose of massage within an 8-week treatment regimen and to further examine durability of response. Participants were 125 adults with OA of the knee, randomized to one of four 8-week regimens of a standardized Swedish massage regimen (30 or 60 min weekly or biweekly) or to a Usual Care control. Outcomes included the Western Ontario and McMaster Universities Arthritis Index (WOMAC), visual analog pain scale, range of motion, and time to walk 50 feet, assessed at baseline, 8-, 16-, and 24-weeks.

Results

WOMAC Global scores improved significantly (24.0 points, 95% CI ranged from 15.3–32.7) in the 60-minute massage groups compared to Usual Care (6.3 points, 95% CI 0.1–12.8) at the primary endpoint of 8-weeks. WOMAC subscales of pain and functionality, as well as the visual analog pain scale also demonstrated significant improvements in the 60-minute doses compared to usual care. No significant differences were seen in range of motion at 8-weeks, and no significant effects were seen in any outcome measure at 24-weeks compared to usual care. A dose-response curve based on WOMAC Global scores shows increasing effect with greater total time of massage, but with a plateau at the 60-minute/week dose.

Conclusion

Given the superior convenience of a once-weekly protocol, cost savings, and consistency with a typical real-world massage protocol, the 60-minute once weekly dose was determined to be optimal, establishing a standard for future trials.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00970008","term_id":"NCT00970008"}}NCT00970008     

Radiation techniques used in patients with breast cancer: Results of a survey in Spain

AimTo evaluate the resources and techniques used in the irradiation of patients with breast cancer after lumpectomy or mastectomy and the status of implementation of new techniques and therapeutic schedules in our country.BackgroundThe demand for cancer care has increased among the Spanish population, as long as cancer treatment innovations have proliferated. Radiation therapy in breast cancer has evolved exponentially in recent years with the implementation of three-dimensional conformal radiotherapy, intensity modulated radiotherapy, image guided radiotherapy and hypofractionation.Material and MethodsAn original survey questionnaire was sent to institutions participating in the SEOR-Mama group (GEORM). In total, the standards of practice in 969 patients with breast cancer after surgery were evaluated.ResultsThe response rate was 70% (28/40 centers). In 98.5% of cases 3D conformal treatment was used. All the institutions employed CT-based planning treatment. Boost was performed in 56.4% of patients: electrons in 59.8%, photons in 23.7% and HDR brachytherapy in 8.8%. Fractionation was standard in 93.1% of patients. Supine position was the most frequent. Only 3 centers used prone position. The common organs of risk delimited were: homolateral lung (80.8%) and heart (80.8%). In 84% histograms were used. An 80.8% of the centers used isocentric technique. In 62.5% asymmetric fields were employed. CTV was delimited in 46.2%, PTV in 65% and both in 38.5%. A 65% of the centers checked with portal films. IMRT and hypofractionation were used in 1% and in 5.5% respectively.ConclusionIn most of centers, 3D conformal treatment and CT-based planning treatment were used. IMRT and hypofractionation are currently poorly implemented in Spain.     

Human demineralised bone matrix as a bone substitute for reconstruction of cystic defects of the lower jaw

Ina retrospective study validated by a standardized clinical and radiologicalexamination, the bone regeneration in 90 patients with cystic mandibulardefectswas examined. In 50 patients bony defect reconstructions with humandemineralised bone matrix (HDBM) were carried out, while in a comparable groupof 40 patients the hollow pockets were left to regenerate bone spontaneously.The bone regeneration after the implantation of human demineralised bone matrix(HDBM) was subjected to a comparative validation. Osteoinductive proteinspresent in HDBM (bone morphogenetic proteins) can diffuse into the implant seatand induce new bone formation (osteoinduction). A markedly faster and morethorough bone regeneration was demonstrated after the surgical therapy ofcysticmandibular lesions with HDBM than without. HDBM also proved to be exceptionallybiocompatible.     

Radiosurgery for multiple brain metastases using volumetric modulated arc therapy: a single institutional series

BackgroundPatients with brain metastases (BM) live longer due to improved diagnosis and oncologic treatments. The association of volumetric modulated arc therapy (VMAT) and image-guided radiation therapy (IGRT) with brain radiosurgery (SRS) allows complex dose distributions and faster treatment delivery to multiple lesions.Materials and methodsThis study is a retrospective analysis of SRS for brain metastasis using VMAT. The primary endpoints were local disease-free survival (LDFS) and overall survival (OS). The secondary outcomes were intracranial disease-free survival (IDFS) and meningeal disease-free survival (MDFS).ResultsThe average number of treated lesions was 5.79 (range: 2–20) per treatment in a total of 113 patients. The mean prescribed dose was 18 Gy (range: 12–24 Gy). The median LDFS was 46 months. The LDFS in 6, 12, and 24 months was for 86%, 79%, and 63%, respectively. Moreover, brain progression occurred in 50 patients. The median overall survival was 47 months. The OS in 75%, 69%, and 61% patients was 6, 12, and 24 months, respectively. IDFS was 6 and 24 months in 35% and 14% patients, respectively. The mean MDFS was 62 months; it was 6 and 24 months for 87% and 83% of patients. Acute severe toxicity was relatively rare. During follow-up, the rates of radionecrosis and neurocognitive impairment were low (10%).ConclusionThe use of VMAT–SRS for multiple BM was feasible, effective, and associated with low treatment-related toxicity rates. Thus, treatment with VMAT is a safe technique to plan to achieve local control without toxicity.     

Biology of brain metastases and novel targeted therapies: Time to translate the research

Brain metastases (BM) occur in 20% to 40% of patients with cancer and result in significant morbidity and poor survival. The main therapeutic options include surgery, whole brain radiotherapy, stereotactic radiosurgery and chemotherapy. Although significant progress has been made in diagnostic and therapeutic methods, the prognosis in these patients remains poor. Furthermore, the poor penetrability of chemotherapy agents through the blood brain barrier (BBB) continues to pose a challenge in the management of this disease. Preclinical evidence suggests that new targeted treatments can improve local tumor control but our clinical experience with these agents remains limited. In addition, several clinical studies with these novel agents have produced disappointing results. This review will examine the knowledge of targeted therapies in BM. The preclinical and clinical evidence of their use in BM induced by breast cancer, non-small cell lung cancer and melanoma will be presented. In addition, we will discuss the role of antiangiogenic and radiosensitising agents in the treatment of BM and the current strategies available to increase BBB permeability. A better understanding of the mechanism of action of these agents will help us to identify the best targets for testing in future clinical studies.     

Role of whole brain radiotherapy in the management of infratentorial metastases from lung and breast cancer

BackgroundBrain metastases (BM) occur in almost one third of patients with systemic malignancies. Only a small number of studies focus on infratentorial location and whole brain radiotherapy (WBRT) as the main non-surgical management. The aim of the study was to compare the prognosis of patients treated with WBRT among patients with supra- or infratentorial lesions.Materials and methodsAt a single center, 263 patients with either breast (BC) or lung (LC) cancer, that had developed BM and received treatment with WBRT, were analyzed during an 8-year period.ResultsA total of 152 patients with BC and 111 with LC were analyzed, median age at the time of BM was 50.7 years, systemic activity other than BM was detected in 91%. Newly diagnosed BM were supratentorial in 40%, infratentorial in 10% and 51% in both locations. Median overall survival was 13 months (95% CI: 11.1–14.8 months), without significant difference between supra- or infratentorial location. WBRT alone was administered in 79% of patients, whereas WBRT with chemtoreapy was provided for 21%.ConclusionIn patients with BM from LC or BC that were not candidates for surgical resection, palliative WBRT appears to be equally effective in those with supra- or infratentorial locations.     

Autologous bone marrow mononuclear cell infusion and hyperbaric oxygen therapy in type 2 diabetes mellitus: an open-label,randomized controlled clinical trial

Background aimsThe use of bone marrow mononuclear cells (BM-MNCs) has achieved great outcomes in clinical practice. We aim to evaluate the efficacy and safety of autologous BM-MNC infusion and hyperbaric oxygen therapy (HOT) in type 2 diabetes mellitus.MethodsThis single-center, randomized, open-label, controlled clinical trial with a factorial design included two phases. The patients received standard medical therapy in the run-in phase; in the treatment phase, patients with glycated hemoglobin of 7.5–9.5% were randomly assigned into four groups and underwent BM-MNC infusion along with HOT (BM-MNC+HOT group), BM-MNC infusion (BM-MNC group), HOT (HOT group) and standard medical therapy (control group), respectively. The area under the curve of C-peptide was recorded as a primary end point. Our research is registered at ClinicalTrials.gov (NCT00767260).ResultsA total of 80 patients completed the follow-up. At 12 months after treatment, the area under the curve of C-peptide (ng/mL per 180 min) of the BM-MNC+HOT group and the BM-MNC group were significantly improved (34.0% and 43.8% from the baseline, respectively). The changes were both significant compared with that in the control group, but no remarkable change was observed in the HOT group. Treatment-related adverse events were mild, including transient abdominal pain (n = 5) and punctual hemorrhage (n = 3).ConclusionsBM-MNC infusion for type 2 diabetes mellitus improves islet function and metabolic control, with mild adverse effects. HOT does not synergize with BM-MNC infusion.     

Re-irradiation after stereotactic body radiotherapy for spine metastases from hepatocellular carcinoma: a case report

Modern radiotherapy machines with refinements in planning software and image-guidance apparatuses have made stereotactic body radiotherapy (SBRT) more widely available as an effective tool in the management of spine metastases. In conventional palliative radiotherapy, the aim has traditionally been pain relief and short-term local control. In contrast, SBRT aims to deliver an ablative dose to enhance local control, with a smaller number of fractions while sparing the organs at risk (OAR), especially the spinal cord. Recently, trials have asserted the role of spine SBRT as an effective modality for durable local control, in addition to achieving pain relief. The quality of evidence for spine SBRT data is maturing, while prospective published trials on re-irradiation SBRT in spine remain sparse. The purpose of the present case report is to share the challenges faced while salvaging a dorsal spine metastasis and ablating a new right adrenal metastatic lesion in proximity of the transplanted liver.     

Validating intramyocardial bone marrow stem cell therapy in combination with coronary artery bypass grafting, the PERFECT Phase III randomized multicenter trial: study protocol for a randomized controlled trial

For the protection of commercial interests, licensing bodies such as the EMA and health technology assessment institutions such as NICE restrict full access to unpublished evidence. Their respective policies on data transparency, however, lack a systematic account of (1) what kinds of commercial interests remain relevant after market approval has been granted, (2) what the specific types of public interest are that may override these commercial interests post approval, and, most importantly, (3) what criteria guide the trade-off between public interest and legitimate measures for the protection of commercial interest. Comparing potential commercial interests with seven specifications of relevant public interest reveals the lack of proportionality inherent in the current practices of EMA and NICE.