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Frontiers in Oncology 2020Both stereotactic body radiotherapy (SBRT) and radiofrequency ablation (RFA) are effective local treatments for hepatocellular carcinoma (HCC), but whether RFA is...
Both stereotactic body radiotherapy (SBRT) and radiofrequency ablation (RFA) are effective local treatments for hepatocellular carcinoma (HCC), but whether RFA is superior to SBRT is still controversial. Therefore, we performed a meta-analysis to compare the treatment outcomes of SBRT with RFA as curable or bridge intention. We searched online databases for studies that compared treatment outcomes for SBRT and RFA. Eligibility criteria included evaluation of local control, overall survival (OS), transplant rate, and post-transplant pathological necrosis. As no randomized clinical trials met the criteria, 10 retrospective studies with a total of 2,732 patients were included. Two studies were in favor of SBRT in local control, two studies preferred RFA in OS, and others reported comparable outcomes for both. SBRT demonstrated significantly higher 1- and 3-year local control than RFA [odds ratio (OR) 0.42, 95% CI 0.24-0.74, = 0.003; and OR 0.54, 95% CI 0.37-0.80, = 0.002, respectively]. However, SBRT reported significantly shorter 1- and 2-year OS (OR 1.52, 95% CI 1.21-1.90, = 0.0003; and OR 1.66, 95% CI 1.38-2.01, < 0.00001, respectively). As bridge treatment, no significant difference was shown in transplant rate and post-transplant pathological necrosis rate (OR 0.57, 95% CI 0.32-1.03, = 0.060; and OR 0.49, 95% CI 0.13-1.82, = 0.290, respectively). This study demonstrates SBRT is able to complete a better local control for HCC than RFA, though the OS is inferior to RFA because of tumor burden or liver profiles of the enrolled studies. Well-designed, randomized, multicenter trials will be required to further investigate the conclusion.
PubMed: 33194569
DOI: 10.3389/fonc.2020.01639 -
International Journal of Radiation... May 2021Dose escalation improves localized prostate cancer disease control, and moderately hypofractionated external beam radiation is noninferior to conventional fractionation....
PURPOSE
Dose escalation improves localized prostate cancer disease control, and moderately hypofractionated external beam radiation is noninferior to conventional fractionation. The evolving treatment approach of ultrahypofractionation with stereotactic body radiation therapy (SBRT) allows possible further biological dose escalation (biologically equivalent dose [BED]) and shortened treatment time.
METHODS AND MATERIALS
The American Association of Physicists in Medicine Working Group on Biological Effects of Hypofractionated Radiation Therapy/SBRT included a subgroup to study the prostate tumor control probability (TCP) with SBRT. We performed a systematic review of the available literature and created a dose-response TCP model for the endpoint of freedom from biochemical relapse. Results were stratified by prostate cancer risk group.
RESULTS
Twenty-five published cohorts were identified for inclusion, with a total of 4821 patients (2235 with low-risk, 1894 with intermediate-risk, and 446 with high-risk disease, when reported) treated with a variety of dose/fractionation schemes, permitting dose-response modeling. Five studies had a median follow-up of more than 5 years. Dosing regimens ranged from 32 to 50 Gy in 4 to 5 fractions, with total BED (α/β = 1.5 Gy) between 183.1 and 383.3 Gy. At 5 years, we found that in patients with low-intermediate risk disease, an equivalent doses of 2 Gy per fraction (EQD2) of 71 Gy (31.7 Gy in 5 fractions) achieved a TCP of 90% and an EQD2 of 90 Gy (36.1 Gy in 5 fractions) achieved a TCP of 95%. In patients with high-risk disease, an EQD2 of 97 Gy (37.6 Gy in 5 fractions) can achieve a TCP of 90% and an EQD2 of 102 Gy (38.7 Gy in 5 fractions) can achieve a TCP of 95%.
CONCLUSIONS
We found significant variation in the published literature on target delineation, margins used, dose/fractionation, and treatment schedule. Despite this variation, TCP was excellent. Most prescription doses range from 35 to 40 Gy, delivered in 4 to 5 fractions. The literature did not provide detailed dose-volume data, and our dosimetric analysis was constrained to prescription doses. There are many areas in need of continued research as SBRT continues to evolve as a treatment modality for prostate cancer, including the durability of local control with longer follow-up across risk groups, the efficacy and safety of SBRT as a boost to intensity modulated radiation therapy (IMRT), and the impact of incorporating novel imaging techniques into treatment planning.
Topics: Dose-Response Relationship, Radiation; Humans; Linear Models; Male; Models, Biological; Models, Theoretical; Probability; Prostatic Neoplasms; Radiation Dose Hypofractionation; Radiosurgery; Relative Biological Effectiveness; Risk; Time Factors; Treatment Outcome; Urethra
PubMed: 32900561
DOI: 10.1016/j.ijrobp.2020.08.014 -
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 -
The British Journal of Radiology Dec 2020In contrast to traditional views of incurability, patients with oligometastatic disease present with an opportunity for disease eradication with aggressive treatment.... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
In contrast to traditional views of incurability, patients with oligometastatic disease present with an opportunity for disease eradication with aggressive treatment. There is mounting evidence in support of the role of stereotactic body radiotherapy (SBRT) in oligometastatic prostate cancer (OMPC).
METHODS
MEDLINE and EMBASE were queried for prospective cohort studies reporting the outcomes of metachronous OMPC treated with SBRT. The primary outcome was overall local control. Secondary outcomes included androgen deprivation therapy-free survival (ADTFS), biochemical recurrence free survival (BCFS), and progression-free survival (PFS). When appropriate, these endpoints were combined in a meta-analysis.
RESULTS
We screened 356 abstracts and identified 10 studies to include in our analysis, with a total of 653 patients and 1,111 lesions. The maximum number of lesions included in any single study ranged from 3 to 5. PET-CT staging occurred in 92.4% of all patients. SBRT dose varied, with BED ranging from 152 to 408. Only one Grade 3 bone toxicity was observed. Meta-analysis reported an overall local control rate of 97% (95% CI, 94-100). Median ADTFS was 24.7 months (95% CI, 20.1-29.2 months). Two-year BCFS, PFS, and ADTFS were 33% (95% CI, 11-55), 39% (95% CI, 24-54), and 52% (95%CI, 41-62), respectively. Patients treated with SBRT were half as likely to experience PSA progression than those on observation when looking at randomized control trial data alone.
CONCLUSION
SBRT appears to be effective in controlling overall disease burden in metachronous OMPC patients and is associated with minimal significant toxicity. The current prospective literature is scarce, and further prospective data are needed to guide treatment recommendations.
ADVANCES IN KNOWLEDGE
This study provides a comprehensive summary of the prospective evidence reporting the outcomes of SBRT in the management of OMPC patients. We quantify the rates of local control, biochemical-free recurrence, progression-free survival, and ADT-free survival through meta-analysis.
Topics: Humans; Male; Neoplasm Metastasis; Prospective Studies; Prostatic Neoplasms; Radiosurgery
PubMed: 32822547
DOI: 10.1259/bjr.20200496 -
Minerva Urologica E Nefrologica = the... Oct 2020The aim of this review was to summarize the available evidence on the role of metastasis-directed therapy (MDT) and/or prostate-targeted therapy (PTT) in the setting of...
INTRODUCTION
The aim of this review was to summarize the available evidence on the role of metastasis-directed therapy (MDT) and/or prostate-targeted therapy (PTT) in the setting of oligometastatic prostate cancer (PCa).
EVIDENCE ACQUISITION
We searched PubMed, the Web of Science, and the Cochrane Library databases. The following keywords were used: ("prostate cancer" OR "prostate carcinoma" OR "prostate neoplasm" OR "prostate tumor") AND ("oligometastatic" OR "oligometastasis" OR "PSMA") AND ("surgery" OR "prostatectomy" OR "radical prostatectomy" OR "cytoreductive" OR "local treatment" OR "radiotherapy" OR "stereotactic" OR "stereotaxic") AND ("survival" OR "mortality").
EVIDENCE SYNTHESIS
After evaluating the selection criteria, 81 studies were evaluated for our endpoints. We included 22 studies for PTT of synchronous mPCa. There have been no randomized studies on cytoreductive prostatectomy (cRP). Four prospective studies showed that cRP was feasible but did not contribute to a positive effect on overall survival (OS). Regarding PTT-radiotherapy, two randomized controlled phase 3 trials showed that OS was improved in men with a low metastatic burden. Regarding MDT of metachronous lymph node recurrence, we included 29 retrospective studies. For MDT of oligometastases, we included 30 studies. One randomized phase 2 trial showed that androgen deprivation therapy-free survival improved with stereotactic body radiation therapy compared to that with surveillance; however, benefits on OS remain unclear.
CONCLUSIONS
We performed a comprehensive overview of the current literature on MDT and PTT. The feasibility of MDT and PTT is supported by several retrospective studies. Nevertheless, there remains a lack of high-quality trials to prove its survival benefits. Results from ongoing prospective trials data are awaited.
Topics: Humans; Male; Molecular Targeted Therapy; Neoplasm Metastasis; Neoplasm Recurrence, Local; Prostatic Neoplasms
PubMed: 32550632
DOI: 10.23736/S0393-2249.20.03779-0 -
The Cochrane Database of Systematic... May 2020This is an updated version of the original Cochrane Review published in Issue 8, 2016. High grade glioma (HGG) is a rapidly growing brain tumour in the supporting cells... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This is an updated version of the original Cochrane Review published in Issue 8, 2016. High grade glioma (HGG) is a rapidly growing brain tumour in the supporting cells of the nervous system, with several subtypes such as glioblastoma (grade IV astrocytoma), anaplastic (grade III) astrocytoma and anaplastic (grade III) oligodendroglioma. Studies have investigated the best strategy to give radiation to people with HGG. Conventional fractionated radiotherapy involves giving a daily radiation dose (called a fraction) of 180 cGy to 200 cGy. Hypofractionated radiotherapy uses higher daily doses, which reduces the overall number of fractions and treatment time. Hyperfractionated radiotherapy which uses a lower daily dose with a greater number of fractions and multiple fractions per day to deliver a total dose at least equivalent to external beam daily conventionally fractionated radiotherapy in the same time frame. The aim is to reduce the potential for late toxicity. Accelerated radiotherapy (dose escalation) refers to the delivery of multiple fractions per day using daily doses of radiation consistent with external beam daily conventionally fractionated radiotherapy doses. The aim is to reduce the overall treatment time; typically, two or three fractions per day may be delivered with a six to eight hour gap between fractions.
OBJECTIVES
To assess the effects of postoperative external beam radiation dose escalation in adults with HGG.
SEARCH METHODS
We searched CENTRAL, MEDLINE Ovid and Embase Ovid to August 2019 for relevant randomised phase III trials.
SELECTION CRITERIA
We included adults with a pathological diagnosis of HGG randomised to the following external beam radiation regimens: daily conventionally fractionated radiotherapy versus no radiotherapy; hypofractionated radiotherapy versus daily conventionally fractionated radiotherapy; hyperfractionated radiotherapy versus daily conventionally fractionated radiotherapy or accelerated radiotherapy versus daily conventionally fractionated radiotherapy.
DATA COLLECTION AND ANALYSIS
The primary outcomes were overall survival and adverse effects. The secondary outcomes were progression free survival and quality of life. We used the standard methodological procedures expected by Cochrane. We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
Since the last version of this review, we identified no new relevant trials for inclusion. We included 11 randomised controlled trials (RCTs) with 2062 participants and 1537 in the relevant arms for this review. There was an overall survival benefit for people with HGG receiving postoperative radiotherapy compared to the participants receiving postoperative supportive care. For the four pooled RCTs (397 participants), the overall hazard ratio (HR) for survival was 2.01 favouring postoperative radiotherapy (95% confidence interval (CI) 1.58 to 2.55; P < 0.00001; moderate-certainty evidence). Although these trials may not have completely reported adverse effects, they did not note any significant toxicity attributable to radiation. Progression free survival and quality of life could not be pooled due to lack of data. Overall survival was similar between hypofractionated and conventional radiotherapy in five trials (943 participants), where the HR was 0.95 (95% CI 0.78 to 1.17; P = 0.63; very low-certainty evidence. The trials reported that hypofractionated and conventional radiotherapy were well tolerated with mild acute adverse effects. These trials only reported one participant in the hypofractionated arm developing symptomatic radiation necrosis that required surgery. Progression free survival and quality of life could not be pooled due to the lack of data. Overall survival was similar between hypofractionated and conventional radiotherapy in the subset of two trials (293 participants) which included participants aged 60 years and older with glioblastoma. For this category, the HR was 1.16 (95% CI 0.92 to 1.46; P = 0.21; high-certainty evidence). There were two trials which compared hyperfractionated radiotherapy versus conventional radiation and one trial which compared accelerated radiotherapy versus conventional radiation. However, the results could not be pooled. The conventionally fractionated radiotherapy regimens were 4500 cGy to 6000 cGy given in 180 cGy to 200 cGy daily fractions, over five to six weeks. All trials generally included participants with World Health Organization (WHO) performance status from 0 to 2 and Karnofsky performance status of 50 and higher. The risk of selection bias was generally low among these RCTs. The number of participants lost to follow-up for the outcome of overall survival was low. Attrition, performance, detection and reporting bias for the outcome of overall survival was low. There was unclear attrition, performance, detection and reporting bias relating to the outcomes of adverse effects, progression free survival and quality of life.
AUTHORS' CONCLUSIONS
Postoperative conventional daily radiotherapy probably improves survival for adults with good performance status and HGG compared to no postoperative radiotherapy. Hypofractionated radiotherapy has similar efficacy for survival compared to conventional radiotherapy, particularly for individuals aged 60 years and older with glioblastoma. There are insufficient data regarding hyperfractionation versus conventionally fractionated radiation (without chemotherapy) and for accelerated radiation versus conventionally fractionated radiation (without chemotherapy). There are HGG subsets who have poor prognosis even with treatment (e.g. glioblastoma histology, older age and poor performance status). These HGG individuals with poor prognosis have generally been excluded from randomised trials based on poor performance status. No randomised trial has compared comfort measures or best supportive care with an active intervention using radiotherapy or chemotherapy in these people with poor prognosis. Since the last version of this review, we found no new relevant studies. The search identified three new trials, but all were excluded as none had a conventionally fractionated radiotherapy arm.
Topics: Adult; Age Factors; Aged; Brain Neoplasms; Cranial Irradiation; Disease-Free Survival; Dose Fractionation, Radiation; Glioma; Humans; Middle Aged; Quality of Life; Randomized Controlled Trials as Topic; Survival Analysis
PubMed: 32437039
DOI: 10.1002/14651858.CD011475.pub3 -
The Cochrane Database of Systematic... Jan 2020This is an update of the review originally published in 2011 and first updated in 2015. In most people with low-grade gliomas (LGG), the primary treatment regimen... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This is an update of the review originally published in 2011 and first updated in 2015. In most people with low-grade gliomas (LGG), the primary treatment regimen remains a combination of surgery followed by postoperative radiotherapy. However, the optimal timing of radiotherapy is controversial. It is unclear whether to use radiotherapy in the early postoperative period, or whether radiotherapy should be delayed until tumour progression occurs.
OBJECTIVES
To assess the effects of early postoperative radiotherapy versus radiotherapy delayed until tumour progression for low-grade intracranial gliomas in people who had initial biopsy or surgical resection.
SEARCH METHODS
Original searches were run up to September 2014. An updated literature search from September 2014 through November 2019 was performed on the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 11), MEDLINE via Ovid (September 2014 to November week 2 2019), and Embase via Ovid (September 2014 to 2019 week 46) to identify trials for inclusion in this Cochrane review update.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that compared early versus delayed radiotherapy following biopsy or surgical resection for the treatment of people with newly diagnosed intracranial LGG (astrocytoma, oligodendroglioma, mixed oligoastrocytoma, astroblastoma, xanthoastrocytoma, or ganglioglioma). Radiotherapy may include conformal external beam radiotherapy (EBRT) with linear accelerator or cobalt-60 sources, intensity-modulated radiotherapy (IMRT), or stereotactic radiosurgery (SRS).
DATA COLLECTION AND ANALYSIS
Three review authors independently assessed the trials for inclusion and risk of bias, and extracted study data. We resolved any differences between review authors by discussion. Adverse effects were also extracted from the study report. We performed meta-analyses using a random-effects model with inverse variance weighting.
MAIN RESULTS
We included one large, multi-institutional, prospective RCT, involving 311 participants; the risk of bias in this study was unclear. This study found that early postoperative radiotherapy was associated with an increase in time to progression compared to observation (and delayed radiotherapy upon disease progression) for people with LGG but did not significantly improve overall survival (OS). The median progression-free survival (PFS) was 5.3 years in the early radiotherapy group and 3.4 years in the delayed radiotherapy group (hazard ratio (HR) 0.59, 95% confidence interval (CI) 0.45 to 0.77; P < 0.0001; 311 participants; 1 trial; low-quality evidence). The median OS in the early radiotherapy group was 7.4 years, while the delayed radiotherapy group experienced a median overall survival of 7.2 years (HR 0.97, 95% CI 0.71 to 1.33; P = 0.872; 311 participants; 1 trial; low-quality evidence). The total dose of radiotherapy given was 54 Gy; five fractions of 1.8 Gy per week were given for six weeks. Adverse effects following radiotherapy consisted of skin reactions, otitis media, mild headache, nausea, and vomiting. Rescue therapy was provided to 65% of the participants randomised to delayed radiotherapy. People in both cohorts who were free from tumour progression showed no differences in cognitive deficit, focal deficit, performance status, and headache after one year. However, participants randomised to the early radiotherapy group experienced significantly fewer seizures than participants in the delayed postoperative radiotherapy group at one year (25% versus 41%, P = 0.0329, respectively).
AUTHORS' CONCLUSIONS
Given the high risk of bias in the included study, the results of this analysis must be interpreted with caution. Early radiation therapy was associated with the following adverse effects: skin reactions, otitis media, mild headache, nausea, and vomiting. People with LGG who underwent early radiotherapy showed an increase in time to progression compared with people who were observed and had radiotherapy at the time of progression. There was no significant difference in overall survival between people who had early versus delayed radiotherapy; however, this finding may be due to the effectiveness of rescue therapy with radiation in the control arm. People who underwent early radiation had better seizure control at one year than people who underwent delayed radiation. There were no cases of radiation-induced malignant transformation of LGG. However, it remained unclear whether there were differences in memory, executive function, cognitive function, or quality of life between the two groups since these measures were not evaluated.
Topics: Brain Neoplasms; Disease-Free Survival; Glioma; Humans; Postoperative Care; Progression-Free Survival; Radiosurgery; Radiotherapy; Randomized Controlled Trials as Topic; Time Factors; Watchful Waiting
PubMed: 31958162
DOI: 10.1002/14651858.CD009229.pub3 -
Neuro-oncology Practice Dec 2019Because less-invasive techniques can obviate the need for brain biopsy in the diagnosis of primary central nervous system lymphoma (PCNSL), it is common practice to wait... (Review)
Review
BACKGROUND
Because less-invasive techniques can obviate the need for brain biopsy in the diagnosis of primary central nervous system lymphoma (PCNSL), it is common practice to wait for a thorough initial work-up, which may delay treatment. We conducted a systematic review and reviewed our own series of patients to define the role of LP and early brain biopsy in the diagnosis of PCNSL.
METHODS
Our study was divided into 2 main sections: 1) systematic review assessing the sensitivity of cerebrospinal fluid (CSF) analysis on the diagnosis of PCNSL, and 2) a retrospective, single-center patient series assessing the diagnostic accuracy and safety of early biopsy in immunocompetent PCNSL patients treated at our institution from 2012 to 2018.
RESULTS
Our systematic review identified 1481 patients with PCNSL. A preoperative LP obviated surgery in 7.4% of cases. Brain biopsy was the preferred method of diagnosis in 95% of patients followed by CSF (3.1%). In our institutional series, brain biopsy was diagnostic in 92.3% of cases (24/26) with 2 cases that required a second procedure for diagnosis. Perioperative morbidity was noted in 7.6% of cases (n = 2) due to hemorrhages after stereotactic brain biopsy that improved at follow-up.
CONCLUSIONS
The diagnostic yield of CSF analyses for PCNSL in immunocompetent patients remains exceedingly low. Our institutional series demonstrates that early biopsy for PCNSL is safe and accurate, and may avert protracted work-ups. We conclude that performing an early brain biopsy in a suspected case of PCNSL is a valid, safe option to minimize diagnostic delay.
PubMed: 31832211
DOI: 10.1093/nop/npz015 -
Journal of Thoracic Oncology : Official... Aug 2019The safety and effectiveness of stereotactic ablative radiotherapy (SABR) in patients with ultra-central lung tumors is currently unclear. We performed a systematic...
INTRODUCTION
The safety and effectiveness of stereotactic ablative radiotherapy (SABR) in patients with ultra-central lung tumors is currently unclear. We performed a systematic review to summarize existing data and identify trends in treatment-related toxicity and local control following SABR in patients with ultra-central lung lesions.
METHODS
We performed a systematic review based on the Preferred Reporting Items for Systemic Reviews and Meta-Analyses guidelines using the PubMed and Embase databases. The databases were queried from dates of inception until September 27, 2018. Studies in the English language that reported treatment-related toxicity and local control outcomes post-SABR for patients with ultra-central lung lesions were included. Guidelines, reviews, non-peer reviewed correspondences, studies focused on re-irradiation, and studies with fewer than five patients were excluded.
RESULTS
A total of 446 studies were identified, with 10 meeting all criteria for inclusion. The total sample size from the identified studies was 250 ultra-central lung patients and all studies were retrospective in design. Radiotherapy dose and fractionation ranged from 30 to 60 Gy in 3 to 12 fractions, with biologically effective doses (BED) ranging from 48 to 138 Gy (median, 78-103 Gy). Median treatment-related grade 3 or greater toxicity was 10% (range, 0-50%). Median treatment-related mortality was 5% (range, 0-22%), most commonly from pulmonary hemorrhage (55%). High-risk indicators for SABR-related mortality included gross endobronchial disease, maximum dose to the proximal bronchial tree greater than or equal to 180 Gy (BED, corresponding to 45 Gy in 5 fractions or 55 Gy in 8 fractions), peri-SABR bevacizumab use, and antiplatelet/anticoagulant use. Median 1-year local control rate was 96% (range, 63%-100%) and 2-year local control rate was 92% (range, 57%-100%).
CONCLUSIONS
SABR for ultra-central lung lesions appears feasible but there is a potential for severe toxicity in patients receiving high doses to the proximal bronchial tree, those with endobronchial disease, and those receiving bevacizumab or anticoagulants around the time of SABR. Prospective studies are required to establish the optimal doses, volumes, and normal tissue tolerances for SABR in this patient population.
Topics: Dose Fractionation, Radiation; Female; Humans; Lung Neoplasms; Male; Radiosurgery; Retrospective Studies
PubMed: 31075543
DOI: 10.1016/j.jtho.2019.04.018 -
International Journal of Molecular... May 2019Immune checkpoint inhibitors (ICI) have represented a revolution in the treatment of non-small-cell lung cancer (NSCLC). To improve these results, combined approaches...
Stereotactic Ablative Radiotherapy Combined with Immune Checkpoint Inhibitors Reboots the Immune Response Assisted by Immunotherapy in Metastatic Lung Cancer: A Systematic Review.
Immune checkpoint inhibitors (ICI) have represented a revolution in the treatment of non-small-cell lung cancer (NSCLC). To improve these results, combined approaches are being tested. The addition of stereotactic ablative radiotherapy (SABR) to ICI seems promising. A systematic review was performed in order to assess the safety and efficacy of SABR-ICI combination. MEDLINE databases from 2009 to March 3, 2019 were reviewed to obtain English language studies reporting clinical outcomes of the combination of ICI-SABR in NSCLC. 18 out of the 429 initial results fulfilled the inclusion criteria and were selected for review. Eighteen articles, including six prospective studies, describing 1736 patients treated with an ICI-SABR combination fulfilled the selection criteria. The reported mean rates for local control and distant/abscopal response rates were 71% and 41%, respectively. Eleven studies reported progression-free survival and overall survival, with a mean of 4.6 and 12.4 months, respectively. Toxicity rates were consistent with the ones attributable to ICI treatment alone. The ICI-SABR combination has a good safety profile and achieves high rates of local control and greater chances of obtaining abscopal responses than SABR alone, with a relevant impact on PFS. More studies are needed to improve patient selection for an optimal benefit from this approach.
Topics: Carcinoma, Non-Small-Cell Lung; Combined Modality Therapy; Humans; Immunotherapy; Lung Neoplasms; Neoplasm Metastasis; Radiosurgery; Treatment Outcome
PubMed: 31052488
DOI: 10.3390/ijms20092173