Stereotactic body radiotherapy (SBRT) for oligometastatic lung tumors from colorectal cancer and other primary cancers in comparison with primary lung cancer

Purpose

To analyze local control of oligometastatic lung tumors (OLTs) compared with that of primary lung cancer after stereotactic body radiotherapy (SBRT).

Materials and methods

Retrospective record review of patients with OLTs who received SBRT with 50 Gy in 5 fractions. Local control rates (LCRs), toxicities, and factors of prognostic significance were assessed.

Results

Twenty-one colorectal OLTs, 23 OLTs from other origins, and 188 primary lung cancers were included. Multivariate analysis revealed only tumor origin was prognostically significant (p < 0.05). The 1-year/2-year LCRs in colorectal OLTs and OLTs from other origins were 80%/72% and 94%/94%, respectively. The LCR in colorectal OLTs was significantly worse than that in OLTs from the other origins and primary lung cancers with pathological and clinical diagnosis (p < 0.05, p < 0.0001 and p < 0.005). Among 44 OLT patients, Grades 2 and 3 radiation pneumonitis were identified in 2 and 1 patients, respectively. No other toxicities of more than Grade 3 occurred.

Conclusion

SBRT for OLTs is tolerable. The LCR for OLTs from origins other than colorectal cancer is excellent. However, LCR for colorectal OLTs is worse than that from other origins. Therefore dose escalation should be considered to achieve good local control for colorectal OLTs.     

Surgical and ablative therapies for the management of adrenal ‘oligometastases’ – A systematic review

Background

We systematically reviewed the literature on the use of surgery, stereotactic ablative body radiotherapy (SABR) and percutaneous catheter ablation (PCA) techniques for the treatment of adrenal metastases to develop evidence-based recommendations.

Methods

A systematic review of the MEDLINE database was performed using structured search terms following PRISMA guidelines. Eligible publications were those published from 1990 to 2012, written in English, had at least five patients treated for adrenal metastasis and reported on patient clinical outcomes (local control, survival and treatment related complications/toxicity). Where possible, pooled 2-year local control and overall survival outcomes were analysed.

Results

Our search strategy produced a total of 45 papers addressing the three modalities – 30 adrenalectomy, nine SABR and six PCA (818, 178 and 51 patients, respectively). There was marked heterogeneity in outcome reporting, patient selection and follow-up periods between studies. The weighted 2-year local control and overall survival for adrenalectomy were 84% and 46%, respectively, compared with 63% and 19%, respectively for the SABR cohort. Only one study of PCA with five patients analysed clinical outcomes, reporting an actuarial local control of 80% at 1 year. Treatment related complications/toxicities were inconsistently reported.

Conclusion

There is insufficient evidence to determine the best local treatment modality for isolated or limited adrenal metastases from any primary tumour. Published data suggests adrenalectomy to be a reasonable treatment approach for isolated adrenal metastasis in suitable patients. SABR is a valid alternative in cases when surgery is not feasible or the operative risk is unacceptable. PCA cannot be recommended until there are more robust studies which include long-term oncological outcomes.     

Oligometastatic disease,the curative challenge in radiation oncology

The concept of oligometastatic disease was first described by Hellman and Weichselbaum in 1995. The mere insight of this concept led to the hypothesis that this disease may be cured using local ablative weapons. Surgery has already demonstrated this hypothesis. Surgery limitations, either technical or due to refusal or associated comorbidity, have led to implement alternative ablative options such as stereotactic body radiation therapy (SBRT). SBRT evolved from (stereotactic radiosurgery) because of the need to irradiate extracranial lesions and has been shown to be safe and effective. SBRT achieves local control rates ranging from 70%-90%, but highly variable survival rates depending on the group analyzed. Series with heterogeneous metastatic sites and tumor origin have reported 20% survival rates at 2-3 years, similar to those achieved with surgery. Despite its excellent results, SBRT still faces significant clinical challenges. Its optimal integration with systemic treatment is unknown, and response assessment is very difficult. However, the greatest challenge lies in selection of patients most likely to remain oligometastatic, those who will most benefit from the technique. Biomarkers, molecular signatures, that accurately predict the biological behavior of malignancy are needed. The expression profile of specific miRNAs has been shown to have a potential in this regard.     

局部治疗在乳腺癌局限性肝转移中的作用

肝脏是乳腺癌远处转移最常见的部位之一。全身治疗是乳腺癌肝转移的标准治疗,但结果并不理想。转移性乳腺癌中存在一类特殊的亚群,即局限性转移。局部治疗,包括转移灶切除术、射频消融、放射治疗等,结合全身治疗可给该部分患者带来生存获益。现就近年来有关乳腺癌局限性肝转移局部治疗的研究结果作一综述。     

Oligometastases in prostate cancer: Ablative treatment

Technological advances in radiotherapy have led to the introduction of techniques such as stereotactic body radiation therapy (SBRT), allowing the administration of ablative doses. The hypothesis that oligometastatic disease may be cured through local eradication therapies has led to the increasing use of SBRT in patients with this type of disease. At the same time, scientific advances are being made to allow the confirmation of clinically suspected oligometastatic status at molecular level. There is growing interest in identifying patients with oligometastatic prostate cancer (PCa) who may benefit from curative intent metastasis-directed therapy, including SBRT. The aim is to complement, replace or delay the introduction of hormone therapy or other systemic therapies. The present review aims to compile the evidence from the main ongoing studies and results on SBRT in relation to oligometastatic PCa; examine aspects where gaps in knowledge or a lack of consensus persist (e.g., optimum schemes, response assessment, identification and diagnosis of oligometastatic patients); and document the lack of first-level evidence supporting the use of such techniques.     

Stereotactic body radiation therapy for lung metastases

Introduction

Stereotactic body radiation therapy (SBRT) has an emerging role in patients affected with pulmonary metastases. Purpose of this study was to evaluate efficacy and tolerability of SBRT in a cohort of patients treated between 2003 and 2009 at our institution.

Methods

A total of 61 patients with oligometastatic lung tumors (single pulmonary nodules in 73.7%) were included in the study. SBRT was performed with a stereotactic body frame and a 3D-conformal technique. Fifty-one patients received 26 Gy in 1 fraction, 22 a dose of 45 Gy in 3 fractions and 3 a dose of 36 Gy in 4 fractions. Primary tumor was lung cancer in 45.7% of patients, colorectal cancer in 21.3% and a variety of other origins in 33%. The primary endpoint was local control, secondary endpoints were survival and toxicity.

Results

After a median follow-up interval of 20.4 months, local control rates at 2 and 3 years were 89% and 83.5%, overall survival 66.5% and 52.5%, cancer-specific survival 75.4% and 67%, progression-free survival 32.4% and 22.3%. Tumor volume was significantly associated to survival, with highest rates in patients with single small tumors. Median survival time was 42.8 months, while median progression-free survival time was 11.9 months. Toxicity profiles were good, with just one case of grade III toxicity (pneumonitis).

Conclusion

This study shows that SBRT is an effective and safe local treatment option for patients with lung metastases. Definitive results are strictly correlated to clinical selection of patients.     

Long-term Outcome of Surgery or Stereotactic Radiotherapy for Lung Oligometastases

Local treatment for pulmonary oligometastases (one to five lesions) using metastasectomy or stereotactic ablative radiotherapy (SABR) was investigated in a cohort that received multidisciplinary tumor board–based treatment decisions. The first choice of treatment was surgery; SABR was recommended in cases of adverse clinical factors. Propensity score–adjusted and unadjusted overall survival was the primary end point; local control and time to failure of a local-only treatment strategy were also analyzed. With a minimum follow-up time of 5.8 years, the 5-year overall survival rate was 41% for surgery (n = 68) and 45% for SABR (n = 42). Again not different for the two modalities, 40% of patients were free from failure of a local-only treatment strategy, and 20% were free from any progression at 5 years. The 5-year local control rate was 83% for SABR and 81% for surgery. Despite treatment selection clearly disadvantaging SABR against surgery, even unadjusted outcome was not better when pulmonary oligometastases were surgically removed rather than irradiated.     

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.     

Management of oligometastatic non-small cell lung cancer patients: Current controversies and future directions

Oligometastatic non-small cell lung cancer (NSCLC) describes an intermediate stage of NSCLC between localized and widely-disseminated disease. This stage of NSCLC is characterized by a limited number of metastases and a more indolent tumor biology. Currently, the management of oligometastatic NSCLC involves radical treatment (radiotherapy or surgery) that targets the metastatic lesions and the primary tumor to achieve disease control. This approach offers the potential to achieve prolonged survival in patients who, in the past, would have only received palliative measures. The optimal therapeutic strategies for the different scenarios of oligometastatic disease (intracranial vs extracranial disease, synchronous vs metachronous) remain undefined. Given the lack of head-to-head studies comparing radiotherapy to surgery in these patients, the decision to apply surgery or radiotherapy (with or without systemic treatment) must be based on prognostic factors that allow us to classify patients. This classification will allow us to select the most appropriate therapeutic strategy on an individualized basis. In the future, the molecular or microRNA profiles will likely improve the treatment selection process. The objective of the present article is to review the most relevant scientific evidence on the management of patients with oligometastatic NSCLC, focusing on the role of radiotherapy and surgery. We also discuss areas of controversy and future directions.     

Oligometastatic breast cancer treated with curative-intent stereotactic body radiation therapy

Purpose Prospective pilot study to assess patient outcome after stereotactic body radiation therapy (SBRT) for limited metastases from breast cancer. Methods Forty patients with ≤5 metastatic lesions received curative-intent SBRT, while 11 patients with >5 lesions, undergoing SBRT to ≤5 metastatic lesions, were treated with palliative-intent. Results Among those treated with curative-intent, 4-year actuarial outcomes were: overall survival of 59%, progression-free survival of 38% and lesion local control of 89%. On univariate analyses, 1 metastatic lesion (versus 2–5), smaller tumor volume, bone-only disease, and stable or regressing lesions prior to SBRT were associated with more favorable outcome. Patients treated with palliative-intent SBRT were spared morbidity and mortality from progression of treated lesions, though all developed further metastatic progression shortly (median 4 months) after enrollment. Conclusions SBRT may yield prolonged survival and perhaps cure in select patients with limited metastases. Palliative-intent SBRT may be warranted for symptomatic or potentially symptomatic metastases.     

Radiothérapie en conditions stéréotaxiques des tumeurs bronchopulmonaires

Stereotactic radiotherapy for lung cancer is a technique that is now well established in the therapeutic arsenal. Protocols are effective, with very high local control rate and an acceptable rate of survival if one takes into account the patient's age and comorbidities. Complications are rare. This review of the literature analyses the whole process of the therapeutic indications and future prospects.     

Central thoracic lesions treated with hypofractionated stereotactic body radiotherapy

Purpose

To investigate the toxicity and outcome after moderately hypofractionated stereotactic body radiotherapy (SBRT) for central thoracic lesions.

Methods

Fifty-three patients undergoing 63 courses of SBRT for central thoracic lesions were retrospectively reviewed. Ninety-eight lesions received 30-63 Gy in 2.5-5.0 Gy fractions using the Novalis ExacTrac^® patient positioning platform.

Results

The 2-year lesion local control was 73%. Larger lesion volume was associated with poorer local control. The 2-year overall survival of patients with Stage I NSCLC, Stages II-III NSCLC and limited metastatic disease was 72%, 12% and 49%, respectively. There were four patient deaths from pulmonary causes, potentially grade 5 toxicities, though three had comorbid pulmonary conditions which may have contributed to the cause of death. One patient died from hemoptysis after undergoing two courses of SBRT to a mediastinal lesion. Most other deaths were attributable to metastatic progression.

Conclusions

Moderately hypofractionated SBRT to central thoracic lesions is effective with respect to local control and toxicity. Further dose escalation can provide an opportunity for better tumor control. Even with less aggressive dose fractionation, pulmonary deaths can occur, though it is difficult to ascertain the extent to which SBRT contributed to the death of patients with comorbid pulmonary conditions.     

Stereotactic Radiosurgery and Stereotactic Body Radiotherapy in the Management of Oligometastatic Disease

Stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT) represent non-invasive, efficacious and safe radiation treatments for the ablation of intracranial and extracranial metastases. Although the use of SRS has been established by level 1 evidence for patients presenting with up to three or four brain metastases for at least a decade, the paradigm of ablating a limited number of extracranial metastases (typically up to five, known as oligometastatic disease) has yet to be proven beyond the few reported but highly encouraging phase II randomised trials. In this overview, we summarise the phase III randomised controlled trials evaluating SRS for intact brain metastases and postoperative surgical cavities and introduce the limited literature and future concepts for treating patients with more than five intracranial metastases. Next, we summarise the published phase II randomised controlled trials specific to SBRT and oligometastatic disease, while briefly describing and contrasting the technical principles and biological mechanisms of SBRT versus conventional radiation. Phase III evidence for SBRT is needed, and we summarise ongoing trials in this overview. Ultimately, SRS and SBRT have become cornerstone therapeutic options for patients with oligometastatic disease and the future is bright for these patients, considering that not so long ago they were considered incurable and relegated to palliation alone.