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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 -
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 -
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 -
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 -
Journal of Radiation Research Jun 2023Japanese national oncological experts convened to evaluate the efficacy and safety of particle beam therapy (PT) for pulmonary, liver and lymph node oligometastases...
Comprehensive analysis of Japanese nationwide cohort data of particle beam therapy for pulmonary, liver and lymph node oligometastases: particle beam therapy versus high-precision X-ray radiotherapy.
Japanese national oncological experts convened to evaluate the efficacy and safety of particle beam therapy (PT) for pulmonary, liver and lymph node oligometastases (P-OM, L-OM and LN-OM, respectively) and to conduct a statistically comparative analysis of the local control (LC) rate and overall survival (OS) rate of PT versus those of X-ray stereotactic body radiotherapy (X-SBRT) and X-ray intensity-modulated radiotherapy (X-IMRT). They conducted [1] an analysis of the efficacy and safety of metastasis-directed therapy with PT for P-OM, L-OM and LN-OM using a Japanese nationwide multi-institutional cohort study data set; [2] a systematic review of X-ray high-precision radiotherapy (i.e. X-SBRT/X-IMRT) and PT for P-OM, L-OM and LN-OM; and [3] a statistical comparison between LC and OS of the cohort data set in PT and that of the extracted historical data set in X-SBRT/X-IMRT from the preceding systematic review. Safety was evaluated as the incidence of grade ≥ 3 adverse events, while statistical comparisons of LC and OS were conducted by estimating the incidence rate ratios (IRR) for local progression and mortality, respectively. This study demonstrated that PT provided durable LC (3-year LC rate: 72.8-83.2%) with acceptable OS (3-year OS rate: 38.5-68.1%) and risk of severe toxicity incidence of 0.8-3.5% in radical metastasis-directed therapy for P-OM, L-OM and LN-OM. Compared to LC with X-SBRT or X-IMRT, LC with PT was potentially superior for P-OM; superior for L-OM; and equivalent for LN-OM. In particular, this study demonstrated that PT may be a new treatment option for L-OM tumors measuring > 5 cm.
Topics: Humans; Cohort Studies; East Asian People; Liver; Radiosurgery; Retrospective Studies; Treatment Outcome; X-Rays; Neoplasm Metastasis
PubMed: 37053162
DOI: 10.1093/jrr/rrad004 -
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 -
Acta Oncologica (Stockholm, Sweden) Nov 2022The aim of this study was to evaluate the current role of local treatment in prostate cancer with a low metastatic burden (or oligometastatic) in relation to survival... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The aim of this study was to evaluate the current role of local treatment in prostate cancer with a low metastatic burden (or oligometastatic) in relation to survival and safety.
METHODS
We performed a meta-analysis of studies published in the MEDLINE, EMBASE, and Cochrane databases until December 2021. Studies comparing local and nonlocal treatment in patients with metastatic prostate cancer were included. The risk of bias within studies was assessed using the Newcastle-Ottawa and Cochrane risk of bias tool. Oligo-metastasis was defined as low-volume metastasis with up to five lesions. The local treatment used was radical prostatectomy or external beam radiation therapy associated with systemic therapy (i.e., androgen deprivation therapy ± abiraterone, docetaxel, enzalutamide, or apalutamide). The endpoints evaluated were overall survival, cancer-specific survival, failure-free survival, and complication rates.
RESULTS
Thirteen studies including 46,541 patients were included. The 5-year overall survival (16.0% vs. 6.5%, respectively; odds ratio (OR) 2.74; 95% confidence interval (CI), 2.18, 3.44; = 0%; < .00001) and 3-year cancer-specific survival (48.2% vs. 26.3%, respectively; OR 1.87; 95% CI: 1.44, 2.44; = 0%; < .00001) were higher in the local treatment group than that of the nonlocal treatment group. In addition, failure-free survival at 3 years was higher in the local treatment group than that of the nonlocal treatment group (40.5% vs. 28.4%, respectively; OR 1.72; 95% CI, 1.38, 2.14; = 0%; < .00001). The low complication rate of Clavien-Dindo grade ≥3 indicated that local treatment is feasible and safe in this setting.
CONCLUSION
Recent data have shown that local treatment combined with systematic therapy, might improve the overall, cancer-specific, and failure-free survivals of patients diagnosed with metastatic prostate cancer. Furthermore, local treatment is both feasible and safe. Further studies evaluating the quality of life of these patients are needed.
Topics: Male; Humans; Prostatic Neoplasms; Androgen Antagonists; Quality of Life; Prostatectomy; Docetaxel
PubMed: 36258673
DOI: 10.1080/0284186X.2022.2132113 -
Pediatric Blood & Cancer Dec 2022Survival of Wilms tumor (WT) is > 90% in high-resource settings but < 30% in low-resource settings. Adapting a standardized surgical approach to WT is challenging in...
BACKGROUND
Survival of Wilms tumor (WT) is > 90% in high-resource settings but < 30% in low-resource settings. Adapting a standardized surgical approach to WT is challenging in low-resource settings, but a local control strategy is crucial to improving outcomes.
OBJECTIVE
Provide resource-sensitive recommendations for the surgical management of WT.
METHODS
We performed a systematic review of PubMed and EMBASE through July 7, 2020, and used the GRADE approach to assess evidence and recommendations.
RECOMMENDATIONS
Initiation of treatment should be expedited, and surgery should be done in a high-volume setting. Cross-sectional imaging should be done to optimize preoperative planning. For patients with typical clinical features of WT, biopsy should not be done before chemotherapy, and neoadjuvant chemotherapy should precede surgical resection. Also, resection should include a large transperitoneal laparotomy, adequate lymph node sampling, and documentation of staging findings. For WT with tumor thrombus in the inferior vena cava, neoadjuvant chemotherapy should be given before en bloc resection of the tumor and thrombus and evaluation for viable tumor thrombus. For those with bilateral WT, neoadjuvant chemotherapy should be given for 6-12 weeks. Neither routine use of complex hilar control techniques during nephron-sparing surgery nor nephron-sparing resection for unilateral WT with a normal contralateral kidney is recommended. When indicated, postoperative radiotherapy should be administered within 14 days of surgery. Post-chemotherapy pulmonary oligometastasis should be resected when feasible, if local protocols allow omission of whole-lung irradiation in patients with nonanaplastic histology stage IV WT with pulmonary metastasis without evidence of extrapulmonary metastasis.
CONCLUSION
We provide evidence-based recommendations for the surgical management of WT, considering the benefits/risks associated with limited-resource settings.
Topics: Child; Humans; Kidney Neoplasms; Wilms Tumor; Nephrectomy; Vena Cava, Inferior; Thrombosis; Retrospective Studies
PubMed: 35929184
DOI: 10.1002/pbc.29906 -
International Journal of Radiation... 2023External beam radiation therapy (EBRT) is commonly used as a palliative treatment for bone metastases of hepatocellular carcinoma (HCC). We planned a hybrid systematic... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
External beam radiation therapy (EBRT) is commonly used as a palliative treatment for bone metastases of hepatocellular carcinoma (HCC). We planned a hybrid systematic review that meta-analyzed the efficacy and feasibility of EBRT and reviewed the literature to answer specific clinical questions.
METHODS
The PubMed, Medline, Embase, and Cochrane Library databases were searched through 1 December 2021. Primary endpoints were overall survival (OS) and response rate (RR). Secondary endpoints were comparative data, including treatment response and survival related to dose escalation, number of metastases, and fractionation scheme. Formal pooled analyses were performed on the primary endpoints, and the secondary endpoints were systematically reviewed. Complications were also reviewed.
RESULTS
Nineteen studies involving 1613 patients with HCC and bone metastases were included. The median OS was 6 months (range: 3-13 months). The pooled one-year OS was 23.1% (95% confidence interval [CI]: 18.4-28.6); pooled pain RR was 81.5% (95% CI: 76.4-85.7) and of pain complete remission was 26.5% (95% CI: 21.7-32.0). Pain response might be related to dose escalation, considering the moderate consistency of results and plausibility, with a low-quality grade of evidence. Considering the indeterminate results, we cannot suggest that dose escalation is correlated with OS. The oligometastasis status might be related to better OS, considering the high consistency of results and plausibility with low to moderate quality of evidence. Hypofractionated EBRT might yield comparable efficacy to conventional EBRT, with a low-quality grade of evidence. There were few complications of grade ≥3, except for hematologic complications, which ranged from 11.5to 34%.
CONCLUSION
EBRT is an efficient and feasible palliative option. Clinical consideration of hematologic complications is necessary. Future studies are needed to increase the quality of evidence for actual clinical questions. Reference to a system of the American Society for Radiation Oncology primary liver cancer clinical guidelines.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Radiation Oncology; Dose Fractionation, Radiation; Bone Neoplasms
PubMed: 35758976
DOI: 10.1080/09553002.2022.2094020