Metastasis-directed Therapy in Prostate Cancer: Prognostic Significance of the ESTRO/EORTC Classification in Oligometastatic Bone Disease

AimsOligometastatic disease (OMD) represents a spectrum of clinical scenarios and various classification systems have been proposed. Bone-only OMD can occur in patients with advanced prostate cancer and validated decision-making tools are needed to assist patient selection for metastasis-directed therapy. The aim of the present study was to determine the prognostic utility of a classification system for OMD.Materials and methodsA retrospective review was conducted of all patients with bone-only oligometastatic prostate cancer treated with stereotactic body radiotherapy (SBRT) since November 2011. SBRT was delivered using CyberKnife® and gantry-based linear accelerator platforms. All patients were classified into oligometastatic states based on the European Society for Radiotherapy and Oncology/European Organisation for Research and Treatment of Cancer (ESTRO/EORTC) classification system. Kaplan–Meier and Cox regression analyses were carried out to determine the prognostic utility of this classification system.ResultsIn total, 105 patients with 145 osseous metastases were treated over 119 sessions. The median follow-up after SBRT was 23 months (interquartile range 10–39.8). Twelve patients had died after a median time of 31 months. The 3-year metastatic progression-free survival was 23% (95% confidence interval 13–32) and the 3-year overall survival was 88% (95% confidence interval 80–96). Patients in a metachronous oligometastatic state were 4.50 (95% confidence interval 1.19–17.10, P = 0.03) times more likely to experience metastatic progression compared with those with synchronous oligometastases, and 6.69 (95% confidence interval 1.05–42.50, P = 0.04) times more likely to experience any failure. Hazard ratio magnitudes increased for patients in a repeat oligometastatic state. The multivariate model for both metastatic progression-free survival and failure-free survival found prostate-specific antigen doubling time <4 months (P = 0.002; P = 0.05) to independently predict for progression.ConclusionThe ESTRO/EORTC classification of OMD predicts for progression in patients treated with SBRT for bone-only oligometastatic prostate cancer at our institution. Further validation in prospective series over multiple tumour sites is needed. These characterisation factors should be assessed in patients considered for metastasis-directed therapy together with established prognostic features.     

Immunotherapy as Single Treatment for Patients With NSCLC With Brain Metastases: A Systematic Review and Meta-Analysis—the META-L-BRAIN Study

IntroductionBrain metastases (BMs) occur in 40% of patients with lung cancer. The activity of immunotherapy in these patients, however, remains controversial, as the cornerstone treatment is radiotherapy (RT). Because RT is associated with adverse events that may impair the quality of life, the possibility of substituting it with a single systemic approach is attractive. Therefore, we performed a systematic review and meta-analysis to evaluate the potential benefit of immune checkpoint inhibitors (ICIs) in patients with NSCLC with untreated BM (unBM).MethodsStudies that enrolled patients with NSCLC treated with ICIs and specifically allowed for unBM were identified by searching the EMBASE, PubMed, Cochrane, and other databases. The outcomes evaluated were intracerebral overall response rate (icORR) and intracerebral disease control rate (icDCR) for unBM, and grades 3 and 4 toxicity rate.ResultsWe included 12 studies with a total of 566 individuals in the final analysis. Anti–programmed cell death protein-1 therapy seems to be active in the central nervous system, with an icORR of 16.4% (95% confidence interval [CI]: 9.8%–24%; I² = 33.17%) and an icDCR of 45% (95% CI: 33.4%–56.9%; I² = 46.91%). In the meta-analysis for icORR (risk ratio = 1.26, 95% CI: 0.57–2.79) and icDCR (risk ratio = 0.88, 95% CI: 0.55–1.43) we did not observe any difference among patients with BM who were treated with RT before ICI start and those who were treated with ICI only.ConclusionsICI seems to be effective as a single treatment for active BM in selected patients with advanced NSCLC.     

Postural balance and oculomotor control are influenced by neck kinaesthetic functions in elite ice hockey players

BackgroundResearch indicates that neck kinaesthetic awareness plays an important role in oculomotor and balance control, however the relationship has not been studied in athletes. As performance in ice hockey demands visual perception acuity during skating, while constantly shifting between unilateral and bilateral stances in sports specific posture more in-depth relationship should be studied.Research questionWhat is the relationship between neck kinaesthetic awareness, postural balance and eye movement control in professional ice hockey players and non-trained individuals?MethodsIn this observational study, centre-of-pressure was measured using force plate in twenty-eight hockey players and thirty non-trained participants during different stances in eyes-opened and eyes-closed conditions. Butterfly test and Head-to-Neutral Relocation test were performed to assess neck kinaesthesia. Horizontal smooth pursuit eye movements were measured using video-oculography. Linear regression was used to determine the relationship between neck kinaesthesia, body sway and oculomotor control.ResultsTime-on-target in Butterfly test was able to predict low to medium proportions of variance in amplitude and velocity parameters for single leg stances in hockey players (R² = .220–.698). Head-to-Neutral Relocation test was able to predict low to medium proportion of variance in average eye movement velocity during first 100 milliseconds of smooth pursuit initiation for both groups (R² = .262–.541).SignificanceFindings from our study suggest that cervical spine afferent input plays an important role in maintaining unilateral postural balance in hockey players, with less evidence presented in controls. Sports specific posture or upper body loading could lead to adaptations in neck proprioception, not frequently considered when searching for balance related injury risk factors or performance deficits. Our study suggests, that in addition to balance control, neck kinaesthesia can also affect oculomotor performance which was present in both groups. This is especially evident when initiating changes in eye movement direction.     

以就业为导向的脊柱相关疾病的推拿教学策略

目的培养脊柱及相关疾病推拿治疗的应用型人才。方法采用编写应用型教材、把教室转移到诊室和示教室、教材-案例“逼真”教学法、创造学生在临床真实环境下的动手操作机会和产-学-研相结合教学法等手段和方法,在内容改革上纳入目前医院和社会机构多使用的规划教材之外的手法技术、现代康复技术和世界各地的脊柱手法技术,拓宽知识面,与临床应用接轨;发挥考试的导向功能,通过改革考试和评价方法,切实培养应用型人才。结果教学效果良好,有效提升了学生临床适应能力和社会生存能力。结论以就业为导向的脊柱及相关疾病的推拿教学模式值得进一步探索。     

A Pre-implementation Study of Volumetric Modulated Arc Therapy for Same-day Planning and Treatment of Vertebral Bone Metastases Within a Rapid-access Palliative Radiotherapy Programme

AimsWe aimed to develop a process for same-day contouring, planning, quality assurance and delivery of volumetric modulated arc therapy (VMAT) for vertebral bone metastases within our institution's rapid-access palliative radiotherapy programme.Materials and methodsTwo thoracic (T6–7, T3–7) and two lumbar (L2–3, L1–5) targets were contoured on computed tomography images acquired from an anthropomorphic phantom and five patient scans. Inverse planning aimed to provide coverage of a prescribed dose of 8 Gy with a combined lung V2Gy < 25% and a combined kidney mean dose <2 Gy. Serial plans were created to identify an efficient combination of six main planning variables specific to our treatment planning system: (i) voxel size (3 mm versus 5 mm), (ii) Monte Carlo statistical uncertainty (1% per calculation versus 3% per control point), (iii) fluence smoothing (medium versus high), (iv) number of iterations of segment shape changes during optimisation (1 versus 5), (v) dose calculation algorithm (Monte Carlo versus pencil beam) and (vi) number of arcs (single versus multiple). Contouring, planning, quality assurance and treatment delivery were timed.ResultsThe combination of planning variables deemed efficient and appropriate was: a 3 mm voxel size, statistical uncertainty of 1% per calculation, medium fluence smoothing, five iterations of segment shape changes, Monte Carlo dose calculation and single full arc delivery. Patient scan contouring times ranged from 7 to 9 min (T6–7), 11–13 min (T3–7), 5–7 min (L2–3) and 8–10 min (L1–5) and planning times ranged from 9 to 15 min (T6–7), 13–25 min (T3–7), 18–25 min (L2–3) and 21–31 min (L1–5). Physics quality assurance times ranged from 15 to 21 min and beam-on times ranged from 3 to 6 min.ConclusionsThe combined elements of VMAT for thoracic and lumbar vertebral bone metastases were completed in under 2 h. This new process makes same-day contouring, planning, quality assurance and treatment delivery of VMAT feasible within our rapid-access palliative radiotherapy programme.     

The impact of PRODIGE 7 on the current worldwide practice of CRS-HIPEC for colorectal peritoneal metastases: A web-based survey and 2021 statement by Peritoneal Surface Oncology Group International (PSOGI)

IntroductionThe PRODIGE 7-trial investigated the additional value of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to cytoreductive surgery (CRS) for patients with colorectal peritoneal metastases (CPM). The results of PRODIGE 7 were presented at the 2018 ASCO meeting showing that 30 min oxaliplatin-based HIPEC did not improve overall survival. The current study investigated the impact of PRODIGE 7 on the worldwide practice of CRS and HIPEC.Materials and methodsCRS-HIPEC experts from 19 countries were invited through the Peritoneal Surface Oncology Group International (PSOGI) to complete an online survey concerning the current CRS-HIPEC practice in their hospital and country, and were asked to appraise the effect of PRODIGE 7.ResultsThe survey was completed by 18/19 experts. Although their personal opinions of CRS-HIPEC were barely influenced by PRODIGE 7, they reported a substantial impact on daily practice. This included a switch towards Mitomycin-C based HIPEC-regimens and prolongation of HIPEC perfusion time, a reduction in the number of referrals from non-HIPEC centers, a reduction in national consensus, the removal of HIPEC from national guidelines, and a reduced reimbursement rate.ConclusionThe PRODIGE 7 has had a major impact on the practice of CRS-HIPEC for CPM worldwide. HIPEC remains an attractive option with potential for control and eradication of disease and further studies into the optimal HIPEC-regimen are urgently needed. Meanwhile, given the complexity of the treatment of patients with CPM, and the proven benefits of optimal CRS, referral of patients with potentially resectable CPM to expert centers is recommended whilst the precise role of HIPEC is further evaluated.     

A guide to assessing post-operative complications following en bloc spinal resection

En-bloc resection of spinal tumours is a complex procedure with significant morbidity and mortality. The extensive resection leaves a large soft tissue and osseous defect requiring reconstruction. Following en-bloc resection, there may be complications relating to both the removal of the tumour and the subsequent reconstruction. This paper outlines the imaging appearances of the frequently encountered complications in our experience. The primary aim is to improve the confidence of the radiologist when reporting imaging following spinal en-bloc resection, however we believe this is also useful for the spinal and orthopaedic surgeons in assessing the patients following en block resection.     

Treatment of metachronous colorectal cancer metastases in the Netherlands: A population-based study

BackgroundThis study aimed to describe the treatment of metachronous colorectal cancer metastases in a recent population-based cohort.MethodPatients with stage I-III colorectal cancer (CRC), diagnosed between January 1st and June 30th^, 2015 who were surgically treated with curative intent were selected from the Netherlands Cancer Registry. Follow-up was at least 3 years after diagnosis of the primary tumour. Treatment of metachronous metastases was categorized into local treatment, systemic treatment, and best supportive care. Overall survival was estimated using Kaplan-Meier method.ResultsOut of 5412 patients, 782 (14%) developed metachronous metastases, of whom 393 (50%) underwent local treatment (LT) with or without systemic therapy, 30% of patients underwent only systemic therapy (ST) and 19% only best supportive care (BSC). The most common metastatic site was the liver (51%) followed by lungs (33%) and peritoneum (22%). LT rates were 69%, 66%, and 44% for liver-only, lung-only and, peritoneal-only metastases respectively. Patients receiving LT and ST were significantly younger than patients receiving LT alone, while patients receiving BSC were significantly older than the other groups (p < 0.001). Patients with liver-only or lung-only metastases had a 3-year OS of 50.2% (43.3–56.7 95% CI) and 61.5% (50.7–70.6 95% CI) respectively. Patients with peritoneal-only disease had a lower 3-year OS, 18.1% (10.1–28.0 95% CI).ConclusionPatients with metastases confined to the liver and lung have the highest rates of local treatment for metachronous metastatic colorectal cancer. The number of patients who underwent local treatment is higher than reported in previous Dutch and international studies.     

Metastatic adult-type non-rhabdomyosarcoma soft tissue sarcomas in children and adolescents: A cohort study from the European paediatric Soft tissue sarcoma Study Group

Background

Limited data exist on the clinical behavior of pediatric non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) with distant metastases at onset, and a clear standard of care has not yet been defined.

Methods

This cohort study reports on pediatric adult-type metastatic NRSTS enrolled in two concurrent prospective European studies, i.e., the randomized BERNIE study and the single-arm MTS 2008 study developed by the European paediatric Soft tissue sarcoma Study Group. Treatment programs were originally designed for patients with metastatic rhabdomyosarcoma, i.e., nine courses of multidrug chemotherapy (with or without bevacizumab in the BERNIE study), followed by 12 cycles of maintenance therapy, whereas radiotherapy and/or surgery (on primary tumor and/or metastases) were delayed until after seven courses of chemotherapy had been administered.

Results

The study included 61 patients <21 years old treated from July 2008 to December 2016. The lung was the site of metastases in 75% of the cases. All patients received multi-agent chemotherapy, 44% had local therapy to primary tumor, and 18% had treatment of metastases. Median time to progression/relapse was 6 months. A high rate of tumor progression was observed during the initial part of the chemotherapy program. With a median follow-up of 41.5 months (range, 2–111 months), 3-year event-free survival and overall survival were 15.4% (95% confidence interval [CI], 7.6–25.7) and 34.9% (95% CI, 22.7–47.5), respectively. There were no statistically significant differences in outcome depending on the type of treatment administered.

Conclusions

The study confirmed the overall poor outcome for patients with metastatic NRSTS, whose treatment remains a challenge.

Plain Language Summary

• Pediatric non-rhabdomyosarcoma soft tissue sarcomas form a heterogeneous group of rare tumors.
• Although recent international studies have defined the standard of care for patients with localized disease, limited data are available on the clinical behavior of patients with distant metastases.
• This study on 61 metastatic cases treated on two prospective European protocols confirms that the chances of survival of such patients are often dismal and a standard treatment is still lacking.