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The Lancet. Oncology Aug 2017Whole brain radiotherapy (WBRT) is the standard of care to improve intracranial control following resection of brain metastasis. However, stereotactic radiosurgery (SRS)... (Comparative Study)
Comparative Study Randomized Controlled Trial
Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial.
BACKGROUND
Whole brain radiotherapy (WBRT) is the standard of care to improve intracranial control following resection of brain metastasis. However, stereotactic radiosurgery (SRS) to the surgical cavity is widely used in an attempt to reduce cognitive toxicity, despite the absence of high-level comparative data substantiating efficacy in the postoperative setting. We aimed to establish the effect of SRS on survival and cognitive outcomes compared with WBRT in patients with resected brain metastasis.
METHODS
In this randomised, controlled, phase 3 trial, adult patients (aged 18 years or older) from 48 institutions in the USA and Canada with one resected brain metastasis and a resection cavity less than 5·0 cm in maximal extent were randomly assigned (1:1) to either postoperative SRS (12-20 Gy single fraction with dose determined by surgical cavity volume) or WBRT (30 Gy in ten daily fractions or 37·5 Gy in 15 daily fractions of 2·5 Gy; fractionation schedule predetermined for all patients at treating centre). We randomised patients using a dynamic allocation strategy with stratification factors of age, duration of extracranial disease control, number of brain metastases, histology, maximal resection cavity diameter, and treatment centre. Patients and investigators were not masked to treatment allocation. The co-primary endpoints were cognitive-deterioration-free survival and overall survival, and analyses were done by intention to treat. We report the final analysis. This trial is registered with ClinicalTrials.gov, number NCT01372774.
FINDINGS
Between Nov 10, 2011, and Nov 16, 2015, 194 patients were enrolled and randomly assigned to SRS (98 patients) or WBRT (96 patients). Median follow-up was 11·1 months (IQR 5·1-18·0). Cognitive-deterioration-free survival was longer in patients assigned to SRS (median 3·7 months [95% CI 3·45-5·06], 93 events) than in patients assigned to WBRT (median 3·0 months [2·86-3·25], 93 events; hazard ratio [HR] 0·47 [95% CI 0·35-0·63]; p<0·0001), and cognitive deterioration at 6 months was less frequent in patients who received SRS than those who received WBRT (28 [52%] of 54 evaluable patients assigned to SRS vs 41 [85%] of 48 evaluable patients assigned to WBRT; difference -33·6% [95% CI -45·3 to -21·8], p<0·00031). Median overall survival was 12·2 months (95% CI 9·7-16·0, 69 deaths) for SRS and 11·6 months (9·9-18·0, 67 deaths) for WBRT (HR 1·07 [95% CI 0·76-1·50]; p=0·70). The most common grade 3 or 4 adverse events reported with a relative frequency greater than 4% were hearing impairment (three [3%] of 93 patients in the SRS group vs eight [9%] of 92 patients in the WBRT group) and cognitive disturbance (three [3%] vs five [5%]). There were no treatment-related deaths.
INTERPRETATION
Decline in cognitive function was more frequent with WBRT than with SRS and there was no difference in overall survival between the treatment groups. After resection of a brain metastasis, SRS radiosurgery should be considered one of the standards of care as a less toxic alternative to WBRT for this patient population.
FUNDING
National Cancer Institute.
Topics: Activities of Daily Living; Adolescent; Adult; Brain Neoplasms; Cognition Disorders; Disease Progression; Disease-Free Survival; Dose Fractionation, Radiation; Female; Follow-Up Studies; Humans; Intention to Treat Analysis; Magnetic Resonance Imaging; Male; Metastasectomy; Middle Aged; Neoplasm Recurrence, Local; Quality of Life; Radiosurgery; Radiotherapy, Adjuvant; Survival Rate; Young Adult
PubMed: 28687377
DOI: 10.1016/S1470-2045(17)30441-2 -
JAMA Surgery Aug 2021Textbook outcome (TO) is a composite measure that captures the most desirable surgical outcomes as a single indicator, yet to date TO has not been defined and assessed...
IMPORTANCE
Textbook outcome (TO) is a composite measure that captures the most desirable surgical outcomes as a single indicator, yet to date TO has not been defined and assessed in the field of laparoscopic liver resection (LLR) and open liver resection (OLR).
OBJECTIVE
To obtain international agreement on the definition of TO in liver surgery (TOLS) and to assess the incidence of TO in LLR and OLR in a large international multicenter database using a propensity-score matched analysis.
DESIGN, SETTING, AND PARTICIPANTS
Patients undergoing LLR or OLR for all liver diseases between January 2011 and October 2019 were analyzed using a large international multicenter liver surgical database. An international survey was conducted among all members of the European-African Hepato-Pancreato-Biliary Association (E-AHPBA) and International Hepato-Pancreato-Biliary Association (IHPBA) to reach agreement on the definition of TOLS. The rate of TOLS was assessed for LLR and OLR before and after propensity-score matching. Factors associated with achieving TOLS were investigated.
MAIN OUTCOMES AND MEASURES
Textbook outcome, with TOLS defined as the absence of intraoperative incidents of grade 2 or higher, postoperative bile leak grade B or C, severe postoperative complications, readmission within 30 days after discharge, in-hospital mortality, and the presence of R0 resection margin.
RESULTS
A total of 8188 patients (4559 LLR; median age, 65 years [interquartile range, 55-73 years]; 2529 were male [55.8%] and 3629 OLR; median age, 64 years [interquartile range, 56-71 years]; 2204 were male [60.7%]) were included in the analysis of whom 69.1% achieved TOLS; 74.8% for LLR and 61.9% for OLR (P < .001). On multivariable analysis, American Society of Anesthesiologists grade III, previous abdominal surgery, histological diagnosis of colorectal liver metastases (odds ratio [OR], 0.656 [95% CI, 0.457-0.940]; P = .02), cholangiocarcinoma, non-CRLM, a tumor size of 30 mm or more, minor resection of posterior/superior segments (OR, 0.716 [95% CI, 0.577-0.887]; P = .002), anatomically major resection (OR, 0.579 [95% CI, 0.418-0.803]; P = .001), and nonanatomical resection (OR, 0.612 [95% CI, 0.476-0.788]; P < .001) were associated with a worse TOLS rate after LLR. For OLR, only histological diagnosis of cholangiocarcinoma (OR, 0.360 [95% CI, 0.214-0.607]; P < .001) and a tumor size of 30 mm or more (30-50 mm = OR, 0.718 [95% CI, 0.565-0.911]; P = .01; 50.1-100 mm = OR, 0.729 [95% CI, 0.554-0.960]; P = .02; >10 cm = OR, 0.550 [95% CI, 0.366-0.826]; P = .004) were associated with a worse TOLS rate.
CONCLUSIONS AND RELEVANCE
In this multicenter study, TOLS was found to be a useful tool for assessing patient-level hospital performance and may have utility in optimizing patient outcomes after LLR and OLR.
Topics: Aged; Carcinoma, Hepatocellular; Cholangiocarcinoma; Colorectal Neoplasms; Databases, Factual; Female; Gallbladder Neoplasms; Hepatectomy; Hospital Mortality; Humans; Intraoperative Complications; Laparoscopy; Liver Neoplasms; Male; Margins of Excision; Metastasectomy; Middle Aged; Neoplasm, Residual; Outcome Assessment, Health Care; Patient Readmission; Postoperative Complications; Propensity Score; Reoperation; Surveys and Questionnaires; Tumor Burden
PubMed: 34076671
DOI: 10.1001/jamasurg.2021.2064 -
The Lancet. Oncology Aug 2017After brain metastasis resection, whole brain radiotherapy decreases local recurrence, but might cause cognitive decline. We did this study to determine if stereotactic... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
After brain metastasis resection, whole brain radiotherapy decreases local recurrence, but might cause cognitive decline. We did this study to determine if stereotactic radiosurgery (SRS) to the surgical cavity improved time to local recurrence compared with that for surgical resection alone.
METHODS
In this randomised, controlled, phase 3 trial, we recruited patients at a single tertiary cancer centre in the USA. Eligible patients were older than 3 years, had a Karnofsky Performance Score of 70 or higher, were able to have an MRI scan, and had a complete resection of one to three brain metastases (with a maximum diameter of the resection cavity ≤4 cm). Patients were randomly assigned (1:1) with a block size of four to either SRS of the resection cavity (within 30 days of surgery) or observation. Patients were stratified by histology of the primary tumour, metastatic tumour size, and number of metastases. The primary endpoint was time to local recurrence in the resection cavity, assessed by blinded central review of brain MRI scans by the study neuroradiologist in the modified intention-to-treat population that analysed patients by randomised allocation but excluded patients found ineligible after randomisation. Participants and other members of the treatment team (excluding the neuroradiologist) were not masked to treatment allocation. The trial is registered with ClinicalTrials.gov, number NCT00950001, and is closed to new participants.
FINDINGS
Between Aug 13, 2009, and Feb 16, 2016, 132 patients were randomly assigned to the observation group (n=68) or SRS group (n=64), with 128 patients available for analysis; four patients were ineligible (three from the SRS group and one from the observation group). Median follow-up was 11·1 months (IQR 4·8-20·4). 12-month freedom from local recurrence was 43% (95% CI 31-59) in the observation group and 72% (60-87) in the SRS group (hazard ratio 0·46 [95% CI 0·24-0·88]; p=0·015). There were no adverse events or treatment-related deaths in either group.
INTERPRETATION
SRS of the surgical cavity in patients who have had complete resection of one, two, or three brain metastases significantly lowers local recurrence compared with that noted for observation alone. Thus, the use of SRS after brain metastasis resection could be an alternative to whole-brain radiotherapy.
FUNDING
National Institutes of Health.
Topics: Adult; Aged; Aged, 80 and over; Brain Neoplasms; Disease-Free Survival; Female; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Male; Metastasectomy; Middle Aged; Neoplasm Recurrence, Local; Radiosurgery; Radiotherapy, Adjuvant; Single-Blind Method; Survival Rate; Time Factors; Tumor Burden; Watchful Waiting; Young Adult
PubMed: 28687375
DOI: 10.1016/S1470-2045(17)30414-X -
Journal of Thoracic Disease Oct 2017Metastasectomy is the most frequent surgical resection undertaken by thoracic surgeons, being the lung the second common site of metastases. The present oncological... (Review)
Review
Metastasectomy is the most frequent surgical resection undertaken by thoracic surgeons, being the lung the second common site of metastases. The present oncological criteria for pulmonary metastasectomy are: (I) the primary cancer need to be controlled or controllable; (II) no extrathoracic metastasis-that is not controlled or controllable-exists; (III) all of the tumor must be resectable, with adequate pulmonary reserve; (IV) there are no alternative medical treatment options with lower morbidity. General favourable prognostic features in patients with pulmonary metastases are: (I) one or few metastases; (II) long disease free interval; (III) normal CEA levels in colorectal cancers. Negative predictive features in patients candidate to pulmonary metastasectomies are: (I) active primary cancer; (II) extrathoracic metastases; (III) inability to obtain surgical radicality; (IV) mediastinal lymphatic spread. The lack of controlled trials and studies limited by short follow-up and small cohorts did not allow to overcome some skepticism; moreover, the heterogeneity of these patients in terms of demographic, biologic and histologic characteristics represents a clear limit even in the largest series. On the basis of present knowledge, without results coming from on-going randomized trials, radical resection, histology, and disease free interval seem to be independent prognostic factors identifying a cohort of patients maximally benefitting from lung metastasectomy.
PubMed: 29119017
DOI: 10.21037/jtd.2017.03.175 -
Journal of Thoracic Disease Apr 2021Repeat surgical resection (redo) for pulmonary metastases is a questionable, albeit intriguing topic. We performed an extensive review of the literature, to specifically... (Review)
Review
Repeat surgical resection (redo) for pulmonary metastases is a questionable, albeit intriguing topic. We performed an extensive review of the literature, to specifically analyze results of redo pulmonary metastasectomies. We reviewed a total of 3,523 papers. Among these, 2,019 were excluded for redundancy and 1,105 because they were not completely retrievable. Out of 399 eligible papers, 183 had missing information or missing abstract, while 96 lacked data on survival. A total of 120 papers dated from 1991 onwards were finally included. Data regarding mortality, major morbidity, prognostic factors and long-term survivals of the first redo pulmonary metastasectomies were retrieved and analyzed. Homogeneity of data was affected by the lack of guidelines for redo pulmonary metastasectomy and the risks of bias when comparing different studies has to be considered. According to the histology sub-types, redo metastasectomies papers were grouped as: colorectal (n=42), sarcomas (n=36), others (n=20) and all histologies (n=22); the total number of patients was 3,015. Data about chemotherapy were reported in half of the papers, whereas targeted or immunotherapy in 9. None of these associated therapies, except chemotherapy in two records, did significantly modify outcomes. Disease-free interval before the redo procedure was the prevailing prognostic factor and nearly all papers showed a significant correlation between patients' comorbidities and prognosis. No perioperative mortality was reported, while perioperative major morbidity was overall quite low. Where available, overall survival after the first redo metastasectomy ranged from 10 to 72 months, with a 5-years survival of approximately 50%. The site of first recurrence after the redo procedure was mainly lung. Despite the data retrievable from literature are heterogeneous and confounding, we can state that redo lung metastasectomy is worthwhile when the lesions are resectable and the perioperative risk is low. At present, there are no "non-surgical" therapeutic options to replace redo pulmonary metastasectomies.
PubMed: 34012616
DOI: 10.21037/jtd-19-4064 -
Thorax Oct 2014Pulmonary metastasectomy is a commonly performed operation and is tending to increase as part of a concept of personalised treatment for advanced cancer. There have been... (Review)
Review
Pulmonary metastasectomy is a commonly performed operation and is tending to increase as part of a concept of personalised treatment for advanced cancer. There have been no randomised trials; belief in effectiveness of metastasectomy is based on registry data and surgical follow-up studies. These retrospective series are comprised predominately of solitary or few metastases with primary resection to metastasectomy intervals longer than 2-3 years. Five-year survival rates of 30-50% are recorded, but as case selection is based on favourable prognostic features, an apparent association between metastasectomy and survival cannot be interpreted as causation. Cancers for which lung metastasectomy is used are considered in four pathological groups. In non-seminomatous germ cell tumour, for which chemotherapy is highly effective, excision of residual pulmonary disease guides future treatment and in particular allows an informed decisions as to further chemotherapy. Sarcoma metastasises predominately to lung and pulmonary metastasectomy for both bone and soft tissues sarcoma is routinely considered as a treatment option but without randomised data. The commonest circumstance for lung and liver metastasectomy is colorectal cancer. Repeated resections and ablations are commonplace but without evidence of effectiveness for either. For melanoma, results are particularly poor, but lung metastases are resected when no other treatment options are available. In this review, the available evidence is considered and the conclusion reached is that in the absence of randomised trials there is uncertainty about effectiveness. A randomised controlled trial, Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC), is in progress and randomised trials in sarcoma seem warranted.
Topics: Colorectal Neoplasms; Global Health; Humans; Lung Neoplasms; Melanoma; Metastasectomy; Sarcoma; Skin Neoplasms; Survival Rate; Treatment Outcome
PubMed: 24415715
DOI: 10.1136/thoraxjnl-2013-204528 -
Annals of Thoracic and Cardiovascular... Jun 2019Pulmonary metastases are a sign of advanced malignancy and an omen of poor prognosis. Once primary tumors metastasize, they become notoriously difficult to treat and... (Review)
Review
Pulmonary metastases are a sign of advanced malignancy and an omen of poor prognosis. Once primary tumors metastasize, they become notoriously difficult to treat and interdisciplinary management often involves a combination of chemotherapy, radiotherapy, and surgery. Over the last 25 years, the emerging body of evidence has recognized the curative potential of pulmonary metastasectomy. Surgical resection of pulmonary metastases is now commonly considered for patients with controlled primary disease, absence of widely disseminated extrapulmonary disease, completely resectable lung metastases, sufficient cardiopulmonary reserve, and lack of a better alternative systemic therapy. Since the development of these selection criteria, other prognostic factors have been proposed to better predict survival and optimize the selection of surgical candidates. Disease-free interval (DFI), completeness of resection, surgical approach, number and laterality of lung metastases, and lymph node metastases all play a dynamic role in determining patient outcomes. There is a definite need to continue reviewing these prognosticators to identify patients who will benefit most from pulmonary metastasectomy and those who should avoid unnecessary loss of lung parenchyma. This literature review aims to explore and synthesize the last 25 years of evidence on the long-term survival, prognostic factors, and patient selection process for pulmonary metastasectomy.
Topics: Disease Progression; Disease-Free Survival; Forecasting; History, 20th Century; History, 21st Century; Humans; Lung Neoplasms; Metastasectomy; Pneumonectomy; Risk Factors
PubMed: 30971647
DOI: 10.5761/atcs.ra.18-00229 -
BJS Open Mar 2022Data regarding adrenal metastasectomy are limited. Here, clinical outcomes, safety, and prognostic factors in patients undergoing adrenal metastasectomy were evaluated...
BACKGROUND
Data regarding adrenal metastasectomy are limited. Here, clinical outcomes, safety, and prognostic factors in patients undergoing adrenal metastasectomy were evaluated in a large nationwide study.
METHODS
Patients undergoing adrenal metastasectomy between 2000 and 2018 were identified in the Danish National Pathology Registry. Medical records were reviewed to confirm eligibility and to collect clinical data. The primary outcome was overall survival (OS). Cox multivariable regression analyses were? adjusted for baseline factors.
RESULTS
In total, 435 patients underwent adrenal metastasectomy; the primary cancer origins were renal (n = 195, 45 per cent), lung (n = 121, 28 per cent), colorectal (n = 50, 11 per cent), and other (n = 69, 16 per cent). The median (interquartile range; i.q.r.) age was 66 (59-71) years, and 280 (64 per cent) were men. The 5-year OS was 31 per cent. The 30-day mortality was 1.8 per cent. Complications were more frequent and severe in patients who underwent open surgery compared with laparoscopic surgery (Clavien-Dindo III-V, 31.5 per cent versus 11.8 per cent respectively, P < 0.001). Factors associated with poor survival included non-radical pR2 resection (hazard ratio (HR) 3.57, 95 per cent c.i. 1.96 to 6.48), tumour size more than 50 mm (HR 1.79, 95 per cent c.i. 1.26 to 2.52), lung cancer origin (HR 1.77, 95 per cent c.i. 1.31 to 2.40), open surgical approach (HR 1.33, 95 per cent c.i. 1.04 to 1.71), presence of extra-adrenal metastases (HR 1.31, 95 per cent c.i. 1.01 to 1.71), and increasing Charlson co-morbidity index factors (HR 1.14 per one-point increase, 95 per cent c.i. 1.03 to 1.27).
CONCLUSION
Adrenal metastasectomy is safe and may result in long-term survival in a subset of patients. Non-radical resection, large tumour size, lung cancer origin, open approach, presence of extra-adrenal metastases, and co-morbidity were associated with inferior outcomes.
Topics: Adrenal Gland Neoplasms; Aged; Female; Humans; Lung Neoplasms; Male; Metastasectomy; Prognosis; Proportional Hazards Models
PubMed: 35442402
DOI: 10.1093/bjsopen/zrac047 -
Frontiers in Surgery 2022Treatment of metastatic renal cell carcinoma (mRCC) has evolved with the development of a variety of systemic agents; however, these therapies alone rarely lead to a... (Review)
Review
Treatment of metastatic renal cell carcinoma (mRCC) has evolved with the development of a variety of systemic agents; however, these therapies alone rarely lead to a complete response. Complete consolidative surgery with surgical metastasectomy has been associated with improved survival outcomes in well-selected patients in previous reports. No randomized control trial exists to determine the effectiveness of metastasectomy. Therefore, reviewing observational studies is important to best determine which patients are most appropriate for metastasectomy for mRCC and if such treatment continues to be effective with the development of new systemic therapies such as immunotherapy. In this narrative review, we discuss the indications for metastasectomies, outcomes, factors associated with improved survival, and special considerations such as location of metastasis, number of metastases, synchronous metastases, and use of systemic therapy. Additionally, alternative treatment options and trials involving metastasectomy will be reviewed.
PubMed: 35965871
DOI: 10.3389/fsurg.2022.943604 -
Current Oncology (Toronto, Ont.) Mar 2022Background: Few studies have described the characteristics and prognostic factors of patients with metastatic extrauterine leiomyosarcoma (euLMS). Therefore, we...
Background: Few studies have described the characteristics and prognostic factors of patients with metastatic extrauterine leiomyosarcoma (euLMS). Therefore, we retrospectively investigated the clinicopathological features, clinical outcomes, and prognostic factors of patients with euLMS. Methods: We recruited 61 patients with metastatic euLMS treated from 2006 to 2020 and collected and statistically analyzed information on patient-, tumor-, and treatment-related factors. The median follow-up period was 21.1 months. Results: Sixty-one patients with euLMS and a median age of 59 years were included. Furthermore, their five-year overall survival (OS) rate was 38.3%. Univariate analysis revealed that primary tumor size >10 cm, synchronous metastasis, initial metastatic sites >1, and no metastasectomy with curative intent were significantly associated with poor OS rate. Multivariate analysis identified primary tumor size >10 cm as an independent prognostic factor for poor OS. Among 24 patients who received metastasectomy with curative intent, the interval from the initial diagnosis to development of metastasis ≤6 months was significantly correlated with unfavorable OS. Among 37 patients who did not receive metastasectomy, chemotherapy after metastasis development was significantly related to better OS. Conclusions: Complete metastasectomy should be considered for metastatic euLMS treatment. Moreover, chemotherapy could prolong survival in patients with metastasis who are ineligible for metastasectomy.
Topics: Humans; Leiomyosarcoma; Metastasectomy; Middle Aged; Multivariate Analysis; Neoplasms, Second Primary; Retrospective Studies
PubMed: 35448161
DOI: 10.3390/curroncol29040187