Whole brain radiotherapy: Prognostic factors and results of a radiation boost delivered through a conventional linear accelerator

Purpose

Assess prognostic factors for overall survival and the potential benefit of a boost in patients treated with whole brain radiation therapy (WBRT).

Methods and materials

From 2002 to 2006, a retrospective analysis was made from 250 unselected consecutive patients with secondary brain metastases from lung cancer, breast cancer and melanoma. Eighteen patients received surgery and were excluded from analysis. Four potential prognostic factors have been studied: primary tumor type, gender, number of metastases and improvement of neurological symptoms after radiation therapy. A subgroup analysis was performed to determine whether an additional boost could potentially improve outcome in patients who presented with less than three metastases, performance status <2, and no surgical resection of their metastasis.

Results

Average follow-up was 10.3 months. Median overall survival was 5.6 months and survival rates at 1 and 2 years were 22.7% and 10%, respectively. Age less than 65 (p < 0.01), neurological improvement after WBRT (p < 0.01), and presence of less than three metastases were significant factors for overall survival in multivariate analysis. When focusing on the selected subgroup (120 assessable patients), median overall survival was 4.0 months in patients with no radiation boost, versus 8.9 months in patients with radiation boost (p = 0.0024).

Conclusions

Survival and prognostic factors were similar to those found in the literature. Boost delivered after WBRT by a conventional particle accelerator could provide a benefit in selected patients, especially for centers that do not have radiotherapy techniques in stereotactic conditions. This warrants further prospective assessment.     

Patterns of distant brain recurrences after radiosurgery alone for newly diagnosed brain metastases: Implications for salvage therapy

Introduction

Single modality radiosurgery (RS) is an established treatment option for patients with brain metastases (BM) with the aim of achieving optimal local control while avoiding toxicity from whole brain radiotherapy (WBRT). Published studies generally lack detailed data on distant brain recurrence (DBR) rates and characteristics. This study describes the patterns of DBR and consequences for salvage treatment in a group of patients treated with RS alone for 1–3 BM.

Materials and methods

Between 2002 and 2012, 443 patients were treated with RS alone in doses ranging 15–24 Gy in 1–3 fractions. Patient selection for RS was performed using triple dose gadolinium-enhanced MRI scans, obtained with slice distance of 2 mm (until 2008), 1.5 mm (2008–2012), and of 1 mm (from 2012). During follow-up, a DBR was observed in 147 patients, but in 20 of these patients (14%) these “new lesions” could retrospectively be seen on the planning MRI scan. These missed metastases had a median size of 2 mm, and in order to study real DBR patterns, these patients were excluded from analysis.

Results

Actuarial DBR rates at 6, 12 and 24 months in the remaining 423 patients were 21%, 41% and 54%, respectively, with a median time to DBR of 5.6 months. In 42% of DBR, a single new lesion was seen, in 70% there were ?3 new lesions. Median diameter of the DBR was 6 mm; 97% of lesions were ?30 mm. Salvage therapy was delivered in 82% of DBR patients, consisting of WBRT (46%), repeated RS (27%), or systemic treatment (9%). A RPA classification system (DBR-RPA), based on WHO performance status and interval between initial RS and diagnosis of DBR, was developed to estimate life expectancy after the development of DBR, which can be used to guide salvage therapy.

Conclusions

In this study of patients treated with RS alone, only 25% of treated patients needed salvage treatment for DBR, and ultimately only 18% of all patients underwent WBRT at any time during follow-up. A three-monthly MRI follow-up scheme identifies DBR at an early stage with respect to size and number of lesions, and most patients were asymptomatic at radiological diagnosis.     

Low incidence of melanoma brain metastasis in the hippocampus

Aims

ANZMTG 01.07 WBRTMel is a phase 3 randomized trial to address the role of whole brain radiation therapy (WBRT) after local treatment of 1–3 melanoma brain metastases. Modern radiation therapy technologies can now conformally spare the hippocampus during WBRT and therefore potentially reduce the risk of neurocognitive deficit. The aims of this study were to report the prevalence of melanoma metastases within the hippocampal sparing region and to identify variables that correlate with the presence of metastases within the hippocampal sparing region.

Methods

The pre-local treatment MRI scans of 77 eligible WBRTMel patients were used to contour the individual metastasis and the hippocampus. The volume, location and closest distance of each metastasis to the hippocampus were recorded. Binary logistic regression was performed to assess the influence of factors on the location of a metastasis within 5 mm of the hippocampus.

Results

The median age was 61 and 66% were male. The distribution of the 115 metastases was frontal (50, 43.5%), parietal (23, 20.0%), temporal (13, 11.2%), occipital (18, 15.7%), cerebellum (10, 8.6%) and pineal gland (1, 1.0%). The median aggregate volume of the metastasis was 3516 mm³. None of the metastases were within the hippocampus. Four patients (5.2%) had metastases within 5 mm of the hippocampus. The median distance from metastasis to the nearest hippocampus was 37.2 mm. Only the total volume of metastases was a significant predictor for the risk of a metastasis within the hippocampal sparing region (OR 1.071, 95% CI: 1.003–1.144, p = 0.040).

Conclusions

This study confirmed a low incidence of melanoma metastasis in the hippocampal sparing region at diagnosis. Given the lack of randomized data on the safety and benefit of hippocampal sparing WBRT, the current WBRTMel trial provides the opportunity to explore the feasibility of this technique.     

The role of stereotactic radiosurgery in the management of patients with newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline

Question

Should patients with newly-diagnosed metastatic brain tumors undergo stereotactic radiosurgery (SRS) compared with other treatment modalities? Target population These recommendations apply to adults with newly diagnosed solid brain metastases amenable to SRS; lesions amenable to SRS are typically defined as measuring less than 3 cm in maximum diameter and producing minimal (less than 1 cm of midline shift) mass effect. Recommendations SRS plus WBRT vs. WBRT alone Level 1 Single-dose SRS along with WBRT leads to significantly longer patient survival compared with WBRT alone for patients with single metastatic brain tumors who have a KPS ≥ 70. Level 2 Single-dose SRS along with WBRT is superior in terms of local tumor control and maintaining functional status when compared to WBRT alone for patients with 1–4 metastatic brain tumors who have a KPS ≥ 70. Level 3 Single-dose SRS along with WBRT may lead to significantly longer patient survival than WBRT alone for patients with 2–3 metastatic brain tumors. Level 4 There is class III evidence demonstrating that single-dose SRS along with WBRT is superior to WBRT alone for improving patient survival for patients with single or multiple brain metastases and a KPS < 70. SRS plus WBRT vs. SRS alone Level 2 Single-dose SRS alone may provide an equivalent survival advantage for patients with brain metastases compared with WBRT + single-dose SRS. There is conflicting class I and II evidence regarding the risk of both local and distant recurrence when SRS is used in isolation, and class I evidence demonstrates a lower risk of distant recurrence with WBRT; thus, regular careful surveillance is warranted for patients treated with SRS alone in order to provide early identification of local and distant recurrences so that salvage therapy can be initiated at the soonest possible time. Surgical Resection plus WBRT vs. SRS ± WBRT Level 2 Surgical resection plus WBRT, vs. SRS plus WBRT, both represent effective treatment strategies, resulting in relatively equal survival rates. SRS has not been assessed from an evidence-based standpoint for larger lesions (>3 cm) or for those causing significant mass effect (>1 cm midline shift). Level 3: Underpowered class I evidence along with the preponderance of conflicting class II evidence suggests that SRS alone may provide equivalent functional and survival outcomes compared with resection + WBRT for patients with single brain metastases, so long as ready detection of distant site failure and salvage SRS are possible. SRS alone vs. WBRT alone Level 3 While both single-dose SRS and WBRT are effective for treating patients with brain metastases, single-dose SRS alone appears to be superior to WBRT alone for patients with up to three metastatic brain tumors in terms of patient survival advantage.     

Phase II trial of gefitinib alone without radiation therapy for Japanese patients with brain metastases from EGFR-mutant lung adenocarcinoma

Background

Brain metastases (BM) are a common in patients with lung cancer. Although whole-brain radiation therapy (WBRT) is the standard therapy, it may have a risk of decline in cognitive function of patients. In this study, we evaluated the efficacy of gefitinib alone without radiation therapy for the treatment of patients with BM from lung adenocarcinoma.

Materials and methods

Eligible patients had BM from lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutations. Gefitinib was given at 250 mg orally once a day until tumor progression or unacceptable toxicity.

Results

Forty-one patients were enrolled. The response rate was 87.8%. No patient experienced grade ≥4 toxicity. The median progression-free survival time was 14.5 months (95% CI, 10.2–18.3 months), and the median overall survival time was 21.9 months (95% CI, 18.5–30.3 months). In compared with L858R, exon 19 deletion was associated with better outcome of patients after treatment with gefitinib in both progression-free (p = 0.003) and overall survival (p = 0.025).

Conclusion

Favorable response of BM to gefitinib even without irradiation was demonstrated. Exon 19 deletion was both a predictive and prognostic marker of patients with BM treated by gefitinib.     

Salvage stereotactic radiosurgery effectively treats recurrences from whole-brain radiation therapy

BACKGROUND.

The purpose of the current study was to examine overall survival (OS) and time to local failure (LF) in patients who received salvage stereotactic radiosurgery (SRS) for recurrent brain metastases (BM) after initial management that included whole‐brain radiation therapy (WBRT).

METHODS.

The records of 1789 BM patients from August 1989 to November 2004 were reviewed. Of these, 111 underwent WBRT as part of their initial management and SRS as salvage. Patients were stratified by Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis class, primary disease, dimension of the largest metastases and number of BM at initial diagnosis, and time to first brain recurrence after WBRT. Overall survival, survival after SRS, and time to local and distant failure were analyzed.

RESULTS.

The median OS from the initial diagnosis of BM was 17.7 months. Median survival after salvage SRS for the entire cohort was 9.9 months. Median survival after salvage SRS was 12.3 months in patients who had their first recurrence >6 months after WBRT versus 6.8 months for those who developed disease recurrence ≤6 months after (P = .0061). Primary tumor site did not appear to affect survival after SRS. Twenty‐eight patients (25%) developed local recurrence after their first SRS with a median time of 5.2 months. A dose <22 grays and lesion size >2 cm were found to be predictive of local failure.

CONCLUSIONS.

In this study, patients who recurred after WBRT and were treated with salvage SRS were found to have good local control and survival after SRS. WBRT provided good initial control, as 45% of these patients failed >6 months after WBRT. Those with a longer time to failure after WBRT had significantly longer survival after SRS. Cancer 2008. © 2008 American Cancer Society.     

Additional radiation boost to whole brain radiation therapy may improve the survival of patients with brain metastases in small cell lung cancer

Background

The role of the dose escalation strategy in brain radiotherapy for small cell lung cancer (SCLC) patients with brain metastases (BMs) has not been identified. This study aims to determine whether an additional radiation boost to whole brain radiation therapy (WBRT) has beneficial effects on overall survival (OS) compared with WBRT-alone.

Methods

A total of 82 SCLC patients who were found to have BMs treated with WBRT plus a radiation boost (n =?33) or WBRT-alone (n =?49) from January 2008 to December 2015 were retrospectively analyzed. All patients were limited-stage (LS) SCLC at the time of the initial diagnosis, and none of them had extracranial metastases prior to detection of BMs. The primary end point was OS.

Results

The median OS for all of the patients was 9.6?months and the 6-, 12- and 24-months OS rates were 69.1, 42.2 and 12.8%, respectively. At baseline, the proportion of more than 3 BMs was significantly higher in the WBRT group than in the WBRT plus boost group (p?=?0.0001). WBRT plus a radiation boost was significantly associated with improved OS in these patients when compared with WBRT-alone (13.4 vs. 8.5?months; p?=?0.004). Further, the survival benefit still remained significant in WBRT plus boost group among patients with 1 to 3 BMs (13.4 vs. 9.6?months; p?=?0.022).

Conclusion

Compared with WBRT-alone, the use of WBRT plus a radiation boost may prolong survival in SCLC patients with BMs. The dose escalation strategy in brain radiotherapy for selected BMs patients with SCLC should be considered.

     

A new survival score for patients with brain metastases who received whole-brain radiotherapy (WBRT) alone

Background and purpose

Survival scores for patients with brain metastasis exist. However, the treatment regimens used to create these scores were heterogeneous. This study aimed to develop and validate a survival score in homogeneously treated patients.

Materials and methods

Eight-hundred-and-eighty-two patients receiving 10 × 3 Gy of WBRT alone were randomly assigned to a test group (N = 441) or a validation group (N = 441). In the multivariate analysis of the test group, age, performance status, extracranial metastasis, and systemic treatment prior to WBRT were independent predictors of survival. The score for each factor was determined by dividing the 6-month survival rate (in %) by 10. Scores were summed and total scores ranged from 6 to 19 points. Patients were divided into four prognostic groups.

Results

The 6-month survival rates were 4% for 6–9 points, 29% for 10–14 points, 62% for 15–17 points, and 93% for 17–18 points (p < 0.001) in the test group. The survival rates were 3%, 28%, 54% and 96%, respectively (p < 0.001) in the validation group.

Conclusions

Since the 6-month survival rates in the validation group were very similar to the test group, this new score (WBRT-30) appears valid and reproducible. It can help making treatment choices and stratifying patients in future trials.     

A meta-analysis evaluating stereotactic radiosurgery, whole-brain radiotherapy, or both for patients presenting with a limited number of brain metastases

BACKGROUND:

To perform a meta‐analysis on newly diagnosed brain metastases patients treated with whole‐brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) boost versus WBRT alone, or in patients treated with SRS alone versus WBRT and SRS boost.

METHODS:

The meta‐analysis primary outcomes were overall survival (OS), local control (LC), and distant brain control (DBC). Secondary outcomes were neurocognition, quality of life (QOL), and toxicity. Using published Kaplan‐Meier curves, results were pooled using hazard ratios (HR).

RESULTS:

Two RCTs reported on WBRT and SRS boost versus WBRT alone. For multiple brain metastases (2‐4 tumors) we conclude no difference in OS, and LC significantly favored WBRT plus SRS boost. Three RCTs reported on SRS alone versus WBRT plus SRS boost (1‐4 tumors). There was no difference in OS despite both LC and DBC significantly favoring WBRT plus SRS boost. Although secondary endpoints could not be pooled for meta‐analysis, those RCTs evaluating SRS alone conclude better neurocognition using the validated Hopkins Verbal Learning Test, no adverse risk in deteriorating Mini‐Mental Status Exam scores or in maintaining performance status, and fewer late toxicities. We conclude insufficient data for QOL outcomes.

CONCLUSIONS:

For selected patients, we conclude no OS benefit for WBRT plus SRS boost compared with SRS alone. Although additional WBRT improves DBC and LC, SRS alone should be considered a routine treatment option due to favorable neurocognitive outcomes, less risk of late side effects, and does not adversely affect the patients performance status. Cancer 2012. © 2011 American Cancer Society.     

Validation of the Disease-Specific GPA for Patients With 1 to 3 Synchronous Brain Metastases in Newly Diagnosed NSCLC

Background

The disease-specific graded prognostic assessment (DS-GPA) for brain metastases is a powerful prognostic tool but has not been validated for patients with synchronous brain metastases (SBM) in newly diagnosed non–small-cell lung cancer (NSCLC).

A clinical nomogram and recursive partitioning analysis to determine the risk of regional failure after radiosurgery alone for brain metastases

Purpose

This investigation defined patient populations at high-, intermediate-, and low-risk of regional failure (RF) after stereotactic radiosurgery (SRS) lesion treatment using clinical nomograms and recursive partitioning analysis (RPA).

Methods and materials

We created a retrospective database compiling 361 oligometastatic brain metastases patients treated with single-modality Linac-based SRS. Logistic analysis was performed to identify factors to be included in a RPA to predict for cumulative RF at 1-year. A 1-year cumulative RF clinical nomogram was constructed and validated (c-index statistic).

Results

Age, number of brain metastases, World Health Organization (WHO) performance status (PS), and maximum gross tumor volume (GTV) size were found to be statistically significant predictors of the primary outcome. RPA classifications were defined as follows: low-risk (<25% 1-year RF): solitary lesion AND age >55Y; intermediate-risk (25–40% 1-year RF): age ?55Y AND solitary lesion OR WHO ? 1 AND 2–3 lesions; and high-risk (>40% 1-year RF): WHO PS = 0 AND 2–3 lesions. These classifications were highly statistically significant (p < 0.01) for RF. A clinical nomogram (containing patient age, lesion number, largest GTV volume, and WHO PS) for the prediction of 1-year cumulative RF was created (c-index 0.69).

Conclusion

A risk-adapted treatment approach can be applied for BM radiosurgery either using RPA categories and/or nomogram-based risk estimates.     

EGFR mutated non-small cell lung cancer patients: More prone to development of bone and brain metastases?

Objectives

Both bone and brain are frequent sites of metastasis in non-small cell lung cancer (NSCLC). Conflicting data exist whether EGFR mutant (+) patients are more prone to develop brain metastases or have a better outcome with brain metastases compared to EGFR/KRAS wildtype (WT) or KRAS+ patients. For bone metastases this has not been studied.

Methods

In this retrospective case-control study all EGFR+ (exons 19 and 21) patients diagnosed at two pathology departments were selected (2004/2008 to 2012). For every EGFR+ patient a consecutive KRAS+ and WT patient with metastatic NSCLC (mNSCLC) was identified. Patients with another malignancy within 2 years of mNSCLC diagnosis were excluded. Data regarding age, gender, performance score, histology, treatment, bone/brain metastases diagnosis, skeletal related events (SRE) and subsequent survival were collected.

Results

189 patients were included: 62 EGFR+, 65 KRAS+, 62 WT. 32%, 35% and 40%, respectively, had brain metastases (p = 0.645). Mean time to brain metastases was 20.8 [±12.0], 10.8 [±9.8], 16.4 [±10.2] months (EGFR+–KRAS+, p = 0.020, EGFR+–WT, p = 0.321). Median post brain metastases survival was 12.1 [5.0–19.1], 7.6 [1.2–14.0], 10.7 [1.5–19.8] months (p = 0.674). 60%, 52% and 50% had metastatic bone disease (p = 0.528). Mean time to development of metastatic bone disease was 13.4 [±10.6], 23.3 [±19.4], 16.4 [±9.6] months (p = 0.201). Median post metastatic bone disease survival was 15.0 [10.6–20.3], 9.0 [5.2–12.9], 3.2 [0.0–6.9] months (p = 0.010). Time to 1st SRE was not significantly different.

Conclusions

Incidence of brain and bone metastases was not different between EGFR+, KRAS+ and WT patients. Post brain metastases survival, time from mNSCLC diagnosis to metastatic bone disease and 1st SRE did not differ either. Post metastatic bone disease survival was significantly longer in EGFR+ patients. Although prevention of SRE's is important for all patients, the latter finding calls for a separate study for SRE preventing agents in EGFR+ patients.     

Emerging Trends in the Management of Brain Metastases from Non-small Cell Lung Cancer

Purpose of Review

To summarize current approaches in the management of brain metastases from non-small cell lung cancer (NSCLC).

Recent Findings

Local treatment has evolved from whole-brain radiotherapy (WBRT) to increasing use of stereotactic radiosurgery (SRS) alone for patients with limited (1–4) brain metastases. Trials have established post-operative SRS as an alternative to adjuvant WBRT following resection of brain metastases. Second-generation TKIs for ALK rearranged NSCLC have demonstrated improved CNS penetration and activity. Current brain metastasis trials are focused on reducing cognitive toxicity: hippocampal sparing WBRT, SRS for 5–15 metastases, pre-operative SRS, and use of systemic targeted agents or immunotherapy.

Summary

The role for radiotherapy in the management of brain metastases is becoming better defined with local treatment shifting from WBRT to SRS alone for limited brain metastases and post-operative SRS for resected metastases. Further trials are warranted to define the optimal integration of newer systemic agents with local therapies.

     

Pulmonary resection of colorectal metastases in patients with or without a history of hepatic metastases

Introduction

In selected patients with isolated colorectal lung or liver metastases resection can provide an increase in overall survival and even cure. Here, we evaluate whether also patients with combined or sequential metastatic disease to liver and lung may still be candidates for surgical resection.

Methods

From 1997 till 2006 39 patients underwent pulmonary metastasectomy. Two subgroups were identified: resection of pulmonary metastases only (PM) and resection of hepatic and later pulmonary metastases (LPM).

Results

Patient characteristics were identical in both groups. Median follow-up in group PM was 35 months and 38 months in group LPM. Two-year survival in group PM was 61%, and in group LPM 81% (p = NS). Five-year survival was 30% and 20% in PM and LPM groups, respectively (p = NS). The median disease free survival was 12 months in the PM group and 13 months in the LPM group.The extent of pulmonary resection had no impact on survival. Complications occurred in seven patients in the PM group and two patients in the LPM group. Complication rate and severity were related to the extent of pulmonary resection. A small group of patients underwent repeated pulmonary resection without serious complications.

Conclusion

Resection of pulmonary colorectal metastases may improve survival, even in patients who underwent hepatic resection for colorectal liver metastases at an earlier stage.     

Phase II trial of patupilone in patients with brain metastases from breast cancer

Background

For patients with progressive breast cancer brain metastasis (BCBM) after whole brain radiotherapy (WBRT), few options exist. Patupilone is an epothilone that crosses the blood–brain barrier. We hypothesized that patupilone would produce a 35% 3-month CNS progression-free survival in women with BCBM after WBRT.

Methods

This multicenter phase II trial included 2 cohorts. Group A included women with progressive BCBM after WBRT. Group B was an exploratory cohort of patients with either leptomeningeal metastases or untreated brain metastases. The primary goal was to observe a 35% 3-month CNS progression-free survival in Group A. The sample size was 45 for Group A and 10 for Group B. Patients received patupilone 10 mg/m² once every 3 weeks until progression. Responses were scored according to the Macdonald criteria.

Results

Fifty-five patients (45 in Group A, 10 in Group B) enrolled. In Group A, the 3-month CNS progression-free survival was 27%, the median overall survival was 12.7 months, and the overall response rate was 9%. In Group B, which enrolled 5 patients with leptomeningeal disease and 5 with no prior WBRT, no responses occurred and 8 patients had CNS progression before 3 months. Systemic responses occurred in 15% of patients, including a complete response in liver metastases. Diarrhea occurred in 87% of patients; 25% had grade 3 and 4 adverse events.

Conclusions

Patupilone in patients with BCBM did not meet the efficacy criteria and had significant gastrointestinal toxicity. Further study of brain-penetrant agents is warranted for patients with CNS metastases from breast cancer.     

Cost-effectiveness Analysis of Stereotactic Radiosurgery Alone Versus Stereotactic Radiosurgery with Upfront Whole Brain Radiation Therapy for Brain Metastases

Aims

Stereotactic radiosurgery (SRS) alone or upfront whole brain radiation therapy (WBRT) plus SRS are the most commonly used treatment options for one to three brain oligometastases. The most recent randomised clinical trial result comparing SRS alone with upfront WBRT plus SRS (NCCTG N0574) has favoured SRS alone for neurocognitive function, whereas treatment options remain controversial in terms of cognitive decline and local control. The aim of this study was to conduct a cost-effectiveness analysis of these two competing treatments.

Is there an oligometastatic state in non-small cell lung cancer? A systematic review of the literature

Objectives

Long-term survival has been observed in patients with oligometastatic non-small cell lung cancer (NSCLC) treated with locally ablative therapies to all sites of metastatic disease. We performed a systematic review of the evidence for the oligometastatic state in NSCLC.

Materials and Methods

A systematic review of MEDLINE, EMBASE and conference abstracts was undertaken to identify survival outcomes and prognostic factors for NSCLC patients with 1–5 metastases treated with surgical metastatectomy, Stereotactic Ablative Radiotherapy (SABR), or Stereotactic Radiosurgery (SRS), according to PRISMA guidelines.

Results

Forty-nine studies reporting on 2176 patients met eligibility criteria. The majority of patients (82%) had a controlled primary tumor and 60% of studies included patients with brain metastases only. Overall survival (OS) outcomes were heterogeneous: 1 year OS: 15–100%, 2 year OS: 18–90% and 5 year OS: 8.3–86%. The median OS range was 5.9–52 months (overall median 14.8 months; for patients with controlled primary, 19 months). The median time to any progression was 4.5–23.7 months (overall median 12 months). Highly significant prognostic factors on multivariable analyses were: definitive treatment of the primary tumor, N-stage and disease-free interval of at least 6–12 months.

Conclusions

Survival outcomes for patients with oligometastatic NSCLC are highly variable, and half of patients progress within approximately 12 months; however, long-term survivors do exist. Definitive treatment of the primary lung tumor and low-burden thoracic tumors are strongly associated with improved long-term survival. The only randomized data to guide management of oligometastatic NSCLC pertains to patients with brain metastases. For other oligometastatic NSCLC patients, randomized trials are needed, and we propose that these prognostic factors be utilized to guide clinical decision making and design of clinical trials.     

Estimation of intracranial failure risk following hippocampal-sparing whole brain radiotherapy

Purpose

To estimate the risk of undertreatment in hippocampal-sparing whole brain radiotherapy (HS-WBRT).

Methods

Eight hundred and fifty six metastases were contoured together with the hippocampi in cranial MRIs of 100 patients. For each metastasis, the distance to the closest hippocampus was calculated. Treatment plans for 10 patients were calculated and linear dose profiles were established. For SCLC and NSCLC, dose–response curves were created based on data from studies on prophylactic cranial irradiation, allowing estimating the risk for intracranial failure.

Results

Only 0.4% of metastases were located inside a hippocampus in 3% of all patients. SCLC showed a relatively high rate of hippocampal metastasis (18.2% of all SCLC patients) and HS-WBRT in a commonly applied fractionation scheme would increase the risk for brain relapse by ∼4% compared to conventional WBRT. NSCLC showed a lower rate of brain metastasis in the hippocampi (2.8%) and HS-WBRT would account for a slightly increased absolute risk of 0.2%.

Conclusions

Prophylactic or therapeutic HS-WBRT is expected to be associated with a low risk of undertreatment. For SCLC, it bears a minimally elevated risk of failure compared to standard WBRT. In NSCLC, HS-WBRT is most likely not associated with a clinically relevant increase in risk of failure.     

Comparison of hepatic recurrences after resection or intraoperative radiofrequency ablation indicated by size and topographical characteristics of the metastases

Aims

Intraoperative use of radiofrequency ablation (IRFA) to treat liver metastases is controversial. The aim of this study was to compare local recurrence rate and survival after IRFA versus resection.

Methods

Three groups from 99 patients were consecutively operated on for 307 liver metastases with 2 years of follow up: group 1, IRFA alone (n = 34); group 2, IRFA plus resection (n = 28); group 3, resection alone (n = 37). The choice of IRFA or resection was made on the basis of the sizes and topographies of the metastases with the goal of achieving R0 treatment.

Results

Mortality was zero; morbidity was 9%, 11% and 11% in the three groups respectively. Median follow-up after surgery was 30 months. Total hepatic recurrences occurred in 59 (60%) patients. Median survival without hepatic recurrence was 17 months with no difference between the three groups (P = 0.474). Total local recurrence occurred in 4 (12%) patients in group 1, in 2 (8%) patients in group 2, and in 2 (6%) patients in group 3. Survival at 2 years was no different in the three groups.

Conclusion

Assessing IRFA indications by size and the topographical characteristics of the liver metastases yields identical local recurrence rates to resection after 2 years of follow up.     

The role of surgical resection in the management of newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline

Question

Should patients with newly-diagnosed metastatic brain tumors undergo open surgical resection versus whole brain radiation therapy (WBRT) and/or other treatment modalities such as radiosurgery, and in what clinical settings? Target population These recommendations apply to adults with a newly diagnosed single brain metastasis amenable to surgical resection. Recommendations Surgical resection plus WBRT versus surgical resection alone Level 1 Surgical resection followed by WBRT represents a superior treatment modality, in terms of improving tumor control at the original site of the metastasis and in the brain overall, when compared to surgical resection alone. Surgical resection plus WBRT versus SRS ± WBRT Level 2 Surgical resection plus WBRT, versus stereotactic radiosurgery (SRS) plus WBRT, both represent effective treatment strategies, resulting in relatively equal survival rates. SRS has not been assessed from an evidence-based standpoint for larger lesions (>3 cm) or for those causing significant mass effect (>1 cm midline shift). Level 3 Underpowered class I evidence along with the preponderance of conflicting class II evidence suggests that SRS alone may provide equivalent functional and survival outcomes compared with resection + WBRT for patients with single brain metastases, so long as ready detection of distant site failure and salvage SRS are possible. Note The following question is fully addressed in the WBRT guideline paper within this series by Gaspar et al. Given that the recommendation resulting from the systematic review of the literature on this topic is also highly relevant to the discussion of the role of surgical resection in the management of brain metastases, this recommendation has been included below. Question Does surgical resection in addition to WBRT improve outcomes when compared with WBRT alone? Target population This recommendation applies to adults with a newly diagnosed single brain metastasis amenable to surgical resection; however, the recommendation does not apply to relatively radiosensitive tumors histologies (i.e., small cell lung cancer, leukemia, lymphoma, germ cell tumors and multiple myeloma). Recommendation Surgical resection plus WBRT versus WBRT alone Level 1 Class I evidence supports the use of surgical resection plus post-operative WBRT, as compared to WBRT alone, in patients with good performance status (functionally independent and spending less than 50% of time in bed) and limited extra-cranial disease. There is insufficient evidence to make a recommendation for patients with poor performance scores, advanced systemic disease, or multiple brain metastases.