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Radiation Oncology (London, England) Mar 2021Due to improved imaging sensitivity, the term "oligometastatic" prostate cancer disease is diagnosed more often, leading to an increasing interest in metastasis-directed...
BACKGROUND
Due to improved imaging sensitivity, the term "oligometastatic" prostate cancer disease is diagnosed more often, leading to an increasing interest in metastasis-directed therapy (MDT). There are two types of radiation based MDT applied when treating oligometastatic disease: (1) stereotactic body radiation therapy (SBRT) generally used for bone metastases; or (2) SBRT for isolated nodal oligometastases combined with prophylactic elective nodal radiotherapy. This review aims to summarize current evidence data, which may shed light on the optimal management of this heterogeneous group of patients.
METHODS
A systematic review of the Medline database through PubMed was performed according to PRISMA guidelines. All relevant studies published up to November 2020 were identified and screened. Fifty-six titles were included. Besides outcome parameters, different prognostic and predictive factors were assessed, including site of metastases, time between primary treatment and MDT, use of systemic therapies, hormone sensitivity, as well as pattern of recurrence.
FINDINGS
Evidence consists largely of retrospective case series and no consistent precise definition of oligometastasis exists, however, most investigators seem to acknowledge the need to distinguish between patients presenting with what is frequently called "synchronous" versus "metachronous" oligometastatic disease. Available data on radiotherapy as MDT demonstrate high local control rates and a small but relevant proportion of patients without progressive disease after 2 years. This holds true for both hormone sensitive and castration resistant prostate cancer diseases. The use of Ga-PSMA PET/CT for staging increased dramatically. Radiation doses and field sizes varied considerably among the studies. The search for relevant prognostic and predictive factors is ongoing.
CONCLUSIONS
To our best knowledge this review on oligometastatic prostate cancer included the largest number of original articles. It demonstrates the therapeutic potential and challenges of MDT for oligometastatic prostate cancer. Prospective studies are under way and will provide further high-level evidence.
Topics: Bone Neoplasms; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Prostatic Neoplasms; Radiosurgery; Radiotherapy Dosage
PubMed: 33750437
DOI: 10.1186/s13014-021-01776-8 -
Lung Cancer (Amsterdam, Netherlands) Aug 2023A systematic review of treatment characteristics, outcomes, and treatment-related toxicities of stereotactic body radiation therapy (SBRT) for pulmonary oligometastases...
PURPOSE
A systematic review of treatment characteristics, outcomes, and treatment-related toxicities of stereotactic body radiation therapy (SBRT) for pulmonary oligometastases served as the basis for development of this International Stereotactic Radiosurgery Society (ISRS) practice guideline.
METHODS
In accordance with PRISMA guidelines, a systematic review was performed of retrospective series with ≥50 patients/lung metastases, prospective trials with ≥25 patients/lung metastases, analyses of specific high-risk situations, and all randomized trials published between 2012 and July 2022 in the MEDLINE or Embase database using the key words "lung oligometastases", "lung metastases", "pulmonary metastases", "pulmonary oligometastases", "stereotactic body radiation therapy (SBRT)" and "stereotactic ablative body radiotherapy (SBRT)". Weighted random effects models were used to calculate pooled outcomes estimates.
RESULTS
Of the 1884 articles screened, 35 analyses (27 retrospective-, 5 prospective, and 3 randomized trials) reporting on treatment of >3600 patients and >4650 metastases were included. The median local control was 90 % (Range: 57-100 %) at 1 year and 79 % (R: 70-96 %) at 5 years. Acute toxicity ≥3 was reported for 0.5 % and late toxicity ≥3 for 1.8 % of patients. A total of 21 practice recommendations covering the areas of staging & patient selection (n = 10), SBRT treatment (n = 10), and follow-up (n = 1) were developed, with agreements rates of 100 %, except for recommendation 13 (83 %).
CONCLUSION
SBRT represents an effective definitive local treatment modality combining high local control rates with low risk of radiation-induced toxicities.
Topics: Humans; Lung Neoplasms; Radiosurgery; Retrospective Studies; Prospective Studies; Radiation Injuries; Lung
PubMed: 37390723
DOI: 10.1016/j.lungcan.2023.107284 -
European Journal of Cancer (Oxford,... May 2022Local treatment (metastasectomy or stereotactic radiotherapy) for oligometastatic disease (OMD) in patients with esophagogastric cancer may improve overall survival... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Local treatment (metastasectomy or stereotactic radiotherapy) for oligometastatic disease (OMD) in patients with esophagogastric cancer may improve overall survival (OS). The primary aim was to identify definitions of esophagogastric OMD. A secondary aim was to perform a meta-analysis of OS after local treatment versus systemic therapy alone for OMD.
METHODS
Studies and study protocols reporting on definitions or OS after local treatment for esophagogastric OMD were included. The primary outcome was the maximum number of organs/lesions considered OMD and the maximum number of lesions per organ (i.e. 'organ-specific' OMD burden). Agreement was considered to be either absent/poor (< 50%), fair (50%-75%), or consensus (≥ 75%). The secondary outcome was the pooled adjusted hazard ratio (aHR) for OS after local treatment versus systemic therapy alone. The ROBINS tool was used for quality assessment.
RESULTS
A total of 97 studies, including 7 study protocols, and 2 prospective studies, were included. OMD was considered in 1 organ with ≤ 3 metastases (consensus). 'Organ-specific' OMD burden could involve bilobar ≤ 3 liver metastases, unilateral ≤ 2 lung metastases, 1 extra-regional lymph node station, ≤ 2 brain metastases, or bilateral adrenal gland metastases (consensus). Local treatment for OMD was associated with improved OS compared with systemic therapy alone based on 6 non-randomized studies (pooled aHR 0.47, 95% CI: 0.30-0.74) and for liver oligometastases based on 5 non-randomized studies (pooled aHR 0.39, 95% CI: 0.22-0.59). All studies scored serious risk of bias.
CONCLUSIONS
Current literature considers esophagogastric cancer spread limited to 1 organ with ≤ 3 metastases or 1 extra-regional lymph node station to be OMD. Local treatment for OMD appeared associated with improved OS compared with systemic therapy alone. Prospective randomized trials are warranted.
Topics: Esophageal Neoplasms; Humans; Metastasectomy; Neoplasm Metastasis; Prospective Studies; Radiosurgery; Stomach Neoplasms
PubMed: 35339868
DOI: 10.1016/j.ejca.2022.02.018 -
European Journal of Cancer (Oxford,... May 2023Local treatment improves the outcomes for oligometastatic disease (OMD, i.e. an intermediate state between locoregional and widespread disseminated disease). However,...
BACKGROUND
Local treatment improves the outcomes for oligometastatic disease (OMD, i.e. an intermediate state between locoregional and widespread disseminated disease). However, consensus about the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer is lacking. The aim of this study was to develop a multidisciplinary European consensus statement on the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer.
METHODS
In total, 65 specialists in the multidisciplinary treatment for oesophagogastric cancer from 49 expert centres across 16 European countries were requested to participate in this Delphi study. The consensus finding process consisted of a starting meeting, 2 online Delphi questionnaire rounds and an online consensus meeting. Input for Delphi questionnaires consisted of (1) a systematic review on definitions of oligometastatic oesophagogastric cancer and (2) a discussion of real-life clinical cases by multidisciplinary teams. Experts were asked to score each statement on a 5-point Likert scale. The agreement was scored to be either absent/poor (<50%), fair (50%-75%) or consensus (≥75%).
RESULTS
A total of 48 experts participated in the starting meeting, both Delphi rounds, and the consensus meeting (overall response rate: 71%). OMD was considered in patients with metastatic oesophagogastric cancer limited to 1 organ with ≤3 metastases or 1 extra-regional lymph node station (consensus). In addition, OMD was considered in patients without progression at restaging after systemic therapy (consensus). For patients with synchronous or metachronous OMD with a disease-free interval ≤2 years, systemic therapy followed by restaging to consider local treatment was considered as treatment (consensus). For metachronous OMD with a disease-free interval >2 years, either upfront local treatment or systemic treatment followed by restaging was considered as treatment (fair agreement).
CONCLUSION
The OMEC project has resulted in a multidisciplinary European consensus statement for the definition, diagnosis and treatment of oligometastatic oesophagogastric adenocarcinoma and squamous cell cancer. This can be used to standardise inclusion criteria for future clinical trials.
Topics: Humans; Delphi Technique; Neoplasms; Europe
PubMed: 36947929
DOI: 10.1016/j.ejca.2023.02.015 -
Defining oligometastatic pancreatic cancer: a systematic review and critical synthesis of consensus.ESMO Open Dec 2023Small retrospective series suggest that local consolidative treatment (LCT) may improve survival in oligometastatic pancreatic ductal adenocarcinoma (PDAC). However, no...
BACKGROUND
Small retrospective series suggest that local consolidative treatment (LCT) may improve survival in oligometastatic pancreatic ductal adenocarcinoma (PDAC). However, no uniform definition of oligometastatic disease (OMD) in PDAC exists; this impedes meaningful conclusions.
PATIENTS AND METHODS
A systematic literature search using PubMed, Web of Science, and Cochrane CENTRAL registries for studies and protocols reporting on definitions and/or LCT of OMD in PDAC was performed. The primary endpoint was the definition of OMD. Levels of agreement were categorized as consensus (≥75% agreement between studies), fair agreement (50%-74%), and absent/poor agreement (<50%).
RESULTS
After screening of 5374 abstracts, the full text of 218 studies was assessed, of which 76 were included in the qualitative synthesis. The majority of studies were retrospective (n = 66, 87%), two were prospective studies and eight were study protocols. Studies investigated mostly liver (n = 38, 51%) and lung metastases (n = 15, 20%). Across studies, less than one-half (n = 32, 42%) reported a definition of OMD, while 44 (58%) did not. Involvement was limited to a single organ (consensus). Additional criteria for defining OMD were the number of lesions (consensus), metastatic site (poor agreement), metastatic size (poor agreement), treatment possibilities (poor agreement), and biomarker response (poor agreement). Liver OMD could involve three or fewer lesions (consensus) and synchronous disease (fair agreement), while lung metastases could involve two or fewer lesions and metachronous disease (consensus). The large majority of studies were at a high risk of bias or did not include any control groups.
CONCLUSION
Definitions of OMD were not used or varied widely between studies hampering across-study comparability and highlighting an unmet need for a consensus. The present study is part of a multistep process that aims to develop an interdisciplinary consensus on OMD in pancreatic cancer.
Topics: Humans; Retrospective Studies; Prospective Studies; Consensus; Lung Neoplasms; Pancreatic Neoplasms
PubMed: 37988953
DOI: 10.1016/j.esmoop.2023.102067 -
Advances in Radiation Oncology Jul 2024Initial studies investigating the combination of local and systemic treatments in advanced esophageal cancer (EC) have conflicting conclusions regarding survival... (Review)
Review
PURPOSE
Initial studies investigating the combination of local and systemic treatments in advanced esophageal cancer (EC) have conflicting conclusions regarding survival benefits. The objective of this systematic review and meta-analysis is to assess the efficacy of the addition of local therapy to systemic treatments in patients with advanced EC.
METHODS AND MATERIALS
A systematic literature search was conducted in the PubMed, EMBASE, and CENTRAL databases. Key eligibility criteria included studies that enrolled patients with histologically confirmed EC or esophagogastric junction cancer with metastasis or recurrence and compared survival benefits between the combined local and systemic treatment group and the systemic treatment alone group. Survival outcomes, represented by hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS), were pooled using a random effects model. The MINORS score was adopted for quality assessment. Risk of bias was statistically examined by Begg's and Egger's tests.
RESULTS
A total of 1 randomized controlled trial (RCT) and 10 qualified retrospective studies including 14,489 patients were identified. Addition of local therapy to systemic treatment significantly improved PFS (HR, 0.52; 95% CI, 0.37-0.73; < .001) and OS (HR, 0.69; 95% CI, 0.58-0.81; < .0001) compared with systemic treatment alone. The subgroup analysis revealed that combined local and systemic treatment conferred a significant survival advantage in both patients with oligometastasis (PFS: HR, 0.45; 95% CI, 0.31-0.64; < .0001; OS: HR, 0.62; 95% CI, 0.48-0.79; < .0001) and recurrence (OS: HR, 0.55; 95% CI, 0.37-0.81; = .002).
CONCLUSIONS
In conclusion, addition of local treatment to systemic therapy can improve survival in patients with advanced EC, particularly in those with oligometastasis or recurrent diseases.
PubMed: 38826154
DOI: 10.1016/j.adro.2024.101522 -
European Journal of Cancer (Oxford,... Jun 2024The OligoMetastatic Esophagogastric Cancer (OMEC) project aims to provide clinical practice guidelines for the definition, diagnosis, and treatment of esophagogastric...
INTRODUCTION
The OligoMetastatic Esophagogastric Cancer (OMEC) project aims to provide clinical practice guidelines for the definition, diagnosis, and treatment of esophagogastric oligometastatic disease (OMD).
METHODS
Guidelines were developed according to AGREE II and GRADE principles. Guidelines were based on a systematic review (OMEC-1), clinical case discussions (OMEC-2), and a Delphi consensus study (OMEC-3) by 49 European expert centers for esophagogastric cancer. OMEC identified patients for whom the term OMD is considered or could be considered. Disease-free interval (DFI) was defined as the time between primary tumor treatment and detection of OMD.
RESULTS
Moderate to high quality of evidence was found (i.e. 1 randomized and 4 non-randomized phase II trials) resulting in moderate recommendations. OMD is considered in esophagogastric cancer patients with 1 organ with ≤ 3 metastases or 1 involved extra-regional lymph node station. In addition, OMD continues to be considered in patients with OMD without progression in number of metastases after systemic therapy. F-FDG PET/CT imaging is recommended for baseline staging and for restaging after systemic therapy when local treatment is considered. For patients with synchronous OMD or metachronous OMD and a DFI ≤ 2 years, recommended treatment consists of systemic therapy followed by restaging to assess suitability for local treatment. For patients with metachronous OMD and DFI > 2 years, upfront local treatment is additionally recommended.
DISCUSSION
These multidisciplinary European clinical practice guidelines for the uniform definition, diagnosis and treatment of esophagogastric OMD can be used to standardize inclusion criteria in future clinical trials and to reduce variation in treatment.
Topics: Humans; Esophageal Neoplasms; Stomach Neoplasms; Europe; Consensus; Neoplasm Metastasis; Delphi Technique
PubMed: 38678762
DOI: 10.1016/j.ejca.2024.114062 -
World Journal of Gastrointestinal... Sep 2019Oesophageal cancer is the eighth most common cancer worldwide. The prognosis of oesophageal cancer patients still remains poor. The 5-year survival rate rarely exceeds...
BACKGROUND
Oesophageal cancer is the eighth most common cancer worldwide. The prognosis of oesophageal cancer patients still remains poor. The 5-year survival rate rarely exceeds 5% in case of metastatic disease. Some patients may however present with oligometastasis which can be treated with loco-regional therapy.
AIM
To assess the current practice regarding the management of patients with oligometastatic oesophageal cancer and identify prognostic factors affecting survival following treatment for oligometastasis.
METHODS
A systematic search of the literature was performed in Cochrance Library, MEDLINE and EMBASE databases from September 1950 to January 2019. Relevant electronic databases were searched for studies assessing the clinical outcome of oligometastasis.
RESULTS
A total of 14 publications were included, of which 12 studies assessing metachronous oligometastasis and 2 on synchronous oligometastasis. All included articles evaluated the specific outcomes of metastasis, management modality and survival outcomes. The majority of the patients presented with oesophageal squamous cell carcinoma. The median disease free interval (time to recurrence) in patients was 19.6 mo and the overall survival reached 30.8 months. Unfavourable prognostic factors were assessed in eight studies and included time to recurrence < 12 mo, large diameter pulmonary lesions (> 20 mm), disease free interval (DFI) < 12 mo, extra-pulmonary metastasis, primary tumour pathological stage III/IV.
CONCLUSION
Oligometastatic oesophageal cancer in selected patients is amenable to loco-regional treatment, and the overall survival of this patient cohort may be improved with patient and tumour-specific treatments.
PubMed: 31558978
DOI: 10.4251/wjgo.v11.i9.741 -
Cancers Jul 2023To analyze the efficacy and safety of surgery compared to radiosurgery (RS), combined or not with whole brain radiotherapy (WBRT), for localized metastatic brain... (Review)
Review
To analyze the efficacy and safety of surgery compared to radiosurgery (RS), combined or not with whole brain radiotherapy (WBRT), for localized metastatic brain disease. A systematic review with meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The inclusion criteria were limited to randomized controlled trials (RCTs) that compared surgery and RS for patients with up to 3 metastases (median diameter ≤ 4 cm). The primary outcomes were represented by overall survival (OS) and local brain progression-free survival (PFS), with the rate of complications as a secondary outcome. The pooled estimates were calculated using random forest models. The risk of bias was evaluated using the RoB2 revised tool and the certainty of the evidence was assessed according to the GRADE guidelines. In total, 11,256 records were identified through database and register searches. After study selection, 3 RCTs and 353 patients were included in the quantitative synthesis. Surgery and RS represented the main intervention arms in all the included RCTs. A low level of evidence suggests that RS alone and surgery followed by WBRT provide an equal rate of local brain PFS in patients with localized metastatic brain disease. There is a very low level of evidence that surgery and RS as main interventions offer equivalent OS in the population investigated. A reliable assessment of the complication rates among surgery and RS was not achievable. The lack of high-certainty evidence either for superiority or equivalence of these treatments emphasizes the need for further, more accurate, RCTs comparing surgery and RS as local treatment in patients with oligometastatic brain disease.
PubMed: 37568618
DOI: 10.3390/cancers15153802 -
European Urology Oncology Oct 2020Metastasis-directed therapy (MDT) in the form of stereotactic ablative radiation therapy (SABR), or in combination with surgical metastasectomy, may have a role in...
Targeting Oligometastasis with Stereotactic Ablative Radiation Therapy or Surgery in Metastatic Hormone-sensitive Prostate Cancer: A Systematic Review of Prospective Clinical Trials.
CONTEXT
Metastasis-directed therapy (MDT) in the form of stereotactic ablative radiation therapy (SABR), or in combination with surgical metastasectomy, may have a role in cancer control and disease progression.
OBJECTIVE
To perform a systematic review of MDT (surgery or SABR) for oligometastatic (up to 10 metastases, recurrent or de novo) hormone-sensitive prostate cancer in addition to or following primary prostate gland treatment.
EVIDENCE ACQUISITION
Medline, Embase, Cochrane Review Database, and clinical trial Databases were systematically searched for clinical trials reporting oncological outcomes and safety. The risk of bias was assessed with the Cochrane 2.0 or ROBINS-I tool.
EVIDENCE SYNTHESIS
From 1025 articles identified, four clinical trials met the prespecified criteria. These included two randomised and two nonrandomised clinical trials (n=169). Baseline prostate-specific antigen level, age, and metastasis ranged from 2.0 to 17.0 ng/ml, 43 to 75 yr, and one to seven lesions, respectively. Nodal, bone, nodal and bone, and visceral metastases were present in 49.7% (84/169), 33.7% (57/169), 15.9% (27/169), and 0.5% (1/169) of patients, respectively. Diagnostic conventional imaging was used in 43.7% (74/169) and positron emission tomography/computerised tomography in 56.2% (95/169) of patients. SABR and surgical metastasectomy with SABR were used in 78.3% (94/120) and 21.6% (26/120) of patients, respectively. Early progression-free survival ranged from 19% to 60%. Local control was reported as 93-100%. Grade II and III SABR toxicities were reported in 8% (8/100) and 1% (1/100) of patients, respectively. Grade IIIa and IIIb surgical complications were reported in 7.69% (2/26) and 0% (0/26) of patients, respectively.
CONCLUSIONS
MDT is a promising experimental therapeutic approach in men with hormone-sensitive oligometastatic prostate cancer. Randomised comparative studies are required to ascertain its role and optimal timing in oligometastatic recurrence and efficacy in de novo synchronous disease.
PATIENT SUMMARY
We looked at the evidence regarding the use of surgery or radiotherapy at target areas of cancer spread in men with newly diagnosed or relapsed advanced (metastatic) prostate cancer. Evidence supports both treatment options as promising approaches, but further large trials are required.
Topics: Ablation Techniques; Clinical Trials as Topic; Humans; Male; Neoplasm Metastasis; Prospective Studies; Prostatic Neoplasms; Radiosurgery
PubMed: 32891600
DOI: 10.1016/j.euo.2020.07.004