Use Of Local Ablative Therapy Research Articles

Efficacy of local ablative therapies in patients with solid tumors treated with immune checkpoint inhibitors and oligoprogression: a single-center analysis.

The concept of oligoprogression reflects a situation where a limited number of metastatic tumor sites have progressed and other metastatic sites are under control with current systemic therapy. The optimal management of oligoprogression remains unclear. In this retrospective study, we evaluated the contribution of local ablative treatment approaches after oligoprogression to progression-free survival and response rates (RRs) in patients with renal cell carcinoma ( N : 5), nonsmall cell lung cancer ( N : 1) and melanoma ( N : 21) who received immunotherapy. We found that patients received local ablative therapies after oligoprogression had longer progression-free survival and higher RR compared to those who did not. Specifically, patients who received concurrent radiotherapy had a median survival time of 24.7 months compared to 14.5 months in those who did not. Our results suggest that local ablative therapies may have a beneficial impact on progression-free survival and RR in patients with oligoprogression who are being treated with immune checkpoint inhibitors. Further studies are needed to confirm these findings and determine the optimal use of local ablative therapies in this setting.

Endoscopic Ultrasound-Guided Local Ablative Therapies for the Treatment of Pancreatic Neuroendocrine Tumors and Cystic Lesions: A Review of the Current Literature.

Since its emergence as a diagnostic modality in the 1980s, endoscopic ultrasound (EUS) has provided the clinician profound access to gastrointestinal organs to aid in the direct visualization, sampling, and subsequent identification of pancreatic pathology. In recent years, advancements in EUS as an interventional technique have promoted the use of local ablative therapies as a minimally invasive alternative to the surgical management of pancreatic neuroendocrine tumors (pNETs) and pancreatic cystic neoplasms (PCNs), especially for those deemed to be poor operative candidates. EUS-guided local therapies have demonstrated promising efficacy in addressing a spectrum of pancreatic neoplasms, while also balancing local adverse effects on healthy parenchyma. This article serves as a review of the current literature detailing the mechanisms, outcomes, complications, and limitations of EUS-guided local ablative therapies such as chemical ablation and radiofrequency ablation (RFA) for the treatment of pNETs and PCNs, as well as a discussion of future applications of EUS-guided techniques to address a broader scope of pancreatic pathology.

P19.10 Evaluation of Local Therapy for Oligoprogressive Disease in Metastatic NSCLC Patients on Immunotherapy

The use of local ablative therapy to treat NSCLC with oligometastatic disease (metastatic disease present in a limited number of sites) and oligoprogressive disease (disease progression in a limited number of sites) has been explored in multiple small prospective and retrospective series. Both Gomez et al 2016 and Iyengar et al 2017 have shown the benefit of radiation therapy as consolidative therapy for oligometastatic disease treated with chemotherapy or targeted therapy. For oligoprogressive disease, numerous retrospective studies indicate a benefit with the use of local ablative therapies in patients receiving targeted therapy.

Radiation in the Treatment of Oligometastatic and Oligoprogressive Disease: Rationale, Recent Data, and Research Questions.

The use of local ablative therapy or metastasis-directed therapy is an emerging management paradigm in oligometastatic and oligoprogressive cancer. Recent randomized evidence has demonstrated that stereotactic ablative radiotherapy (SABR) targeting all metastatic deposits is tolerable and can improve progression-free and overall survival. While SABR is noninvasive, minimally toxic, and generally safe, rare grade 5 events have been reported. Given this and recognizing the often-uncertain prognosis of patients with metastatic disease, equipoise persists regarding the therapeutic window within which to deploy SABR for this indication. Ongoing phase III trials are aimed at validating the demonstrated safety, tolerability, and survival benefits while also refining patient selection, possibly with the aid of novel biomarkers. This narrative review of the role of SABR in oligometastatic and oligoprogressive disease summarizes recent randomized evidence and ongoing clinical trials, discusses our rationale for treatment and key management principles, and posits that SABR should be considered the preferred modality for multisite, metastasis-directed ablative therapy.

The Dandelion Dilemma Revisited for Oligoprogression: Treat the Whole Lawn or Weed Selectively?

Oligoprogressive disease is a relatively new clinical concept describing progression at only a few sites of metastasis in patients with otherwise controlled widespread disease. In the era of well-tolerated targeted treatments, resistance inevitably occurs and overcoming this is a challenge. Local ablative therapy for oligoprogressive disease may allow the continuation of systemic treatments by overcoming the few sub-clones that have developed resistance. Stereotactic body radiotherapy is now frequently used in treating oligometastatic disease using ablative doses with minimally invasive techniques and acceptable toxicity. We discuss the current retrospective clinical evidence base supporting the use of local ablative therapy for oligoprogression in metastatic patients on targeted treatments within multiple tumour sites. As there is currently a lack of published prospective data available, the best management for these patients remains unclear. We discuss current trials in recruitment and the potential advancements in treating this group of patients with stereotactic radiotherapy.

Clinical outcome of stereotactic body radiotherapy for lung-only oligometastatic head and neck squamous cell carcinoma: Is the deferral of systemic therapy a potential goal?

ObjectivesOligometastatic head and neck squamous cell carcinoma (HNSCC) is a rare entity with no evidence-based treatment recommendations available to support the use of local ablative therapies. The aim of our study was to report on the clinical benefit of stereotactic body radiotherapy (SBRT) for patients with lung-only oligometastases, defined by the presence of 1 to 5 pulmonary lesions. Material and MethodsSBRT was applied in case of single lesions deemed amenable to local treatment only (“de novo” pattern) or after first line chemotherapy at time of disease oligoprogression (“induced” pattern). To assess the potential deferral of systemic therapy in both time points, we analyzed time to progression (TTP) defined as the time from the last day of SBRT to disease progression or death from any cause. Cox regression analysis was performed to identify predictive factors of better outcome. ResultsTwenty-seven patients were retrospectively evaluated. The majority (81.5%) had HPV negative disease and a “de novo” oligometastatic pattern (78.6%). The median maximum lesion diameter and target size were 1.5 cm and 22.7 cc, respectively. At a median follow-up of 22 months (range 6–73), the median TTP was 10 months (95% CI: 9.5–21.1), with 1- and 2-year rates of 56.2% and 35%, respectively. The objective response rate at 3 months after SBRT was 75%. At multivariate analysis baseline T3/T4 stage had a HR for worse outcome of 5.38 (p = 0.033). Acute toxicity was minimal (G1/G2 of 14.8%). ConclusionIn properly selected oligometastatic patients, SBRT has potential for sustained deferral of systemic treatment.

Local ablative therapy of oligoprogressive TKI-treated thyroid cancer.

Metastatic cancer patients generally respond well to treatment with tyrosine kinase inhibitors (TKIs). However, TKI resistance occurs in almost all cases and often leads to a change in treatment. Recent guidelines, including thyroid cancer, raised the possibility of locally treating TKI-resistant oligoprogressive disease, i.e., one or a few progressing lesions in an otherwise treatment-responsive metastatic cancer, thereby obviating the need to change the ongoing TKI. To determine the benefits of this intervention, we reviewed studies on the use of LAT for TKI-treated oligoprogressive cancers. We found that in non-small cell lung cancer at least, LAT prolongs disease control and the duration of exposure to a TKI irrespective of the LAT used. Moreover, we reviewed the local ablative therapies (LATs) that are feasible for the local control of oligoprogressive thyroid cancer. Lastly, we report two illustrative cases of patients with oligoprogressive thyroid cancer treated with two different LATs while on therapy with TKIs. Both LATs extended the duration of disease control and the time of exposure to the ongoing TKI, thereby indicating that LAT is a favorable option for TKI-treated oligoprogressive thyroid cancer. Prospective randomized studies are needed to verify the benefit of LATs in terms of progression-free and overall survival in this increasingly frequent clinical setting.

Factors affecting local control of pulmonary oligometastases treated with stereotactic body radiotherapy

Background: Oligometastases refers to a state of limited metastatic disease. The use of local ablative therapies to patients with oligometastases can result in durable state of remission or long-term cure. Stereotactic body radiotherapy (SBRT) is a highly conformal radiation technique that delivers ablative doses to the target. The study aimed to evaluate local control (LC) and identify factors associated with poor LC in patients with pulmonary oligometastases treated with SBRT. Primary endpoint of the study was to assess LC; secondary endpoint was to determine factors associated with LC.Material and methods: Criteria used for selection of patients with oligometastases included: metastatic disease limited to a maximum of two organs and no more than five metastatic lesions at time of treatment. Peripheral tumors were treated with 51–60 Gy in three fractions or a single fraction of 30 Gy. Central tumors received a dose of 45–60 Gy in 5–8 fractions.Results: In 206 patients, 327 pulmonary oligometastases were treated with SBRT. Median follow-up was 22 months (range 2–100). LC at 2 and 3 years was 85% and 83%, respectively. On univariate analysis, biological equivalent dose assuming an α/β ratio of 10 (BED10) < 100 Gy (HR 3.09), single-fraction SBRT (HR 2.83), synchronous metastasis (HR 1.99), and pre-SBRT chemotherapy (HR 2.79) were significantly associated with inferior LC. In the multivariable analysis BED10 <100 Gy (HR 3.59), pre-SBRT chemotherapy (HR 2.61) and presence of synchronous metastasis (HR 2.21) remained independently associated with poor LC.Conclusions: SBRT achieved an excellent LC of 85% at 2 years. Although retrospective in nature, our study identified three factors associated with inferior LC. These factors may help to refine SBRT practice for pulmonary oligometastases in the future.

Managing Resistance to EFGR- and ALK-Targeted Therapies.

Targeted therapies have transformed the management of non-small cell lung cancer (NSCLC) and placed an increased emphasis on stratifying patients on the basis of genetic alterations in oncogenic drivers. To date, the best characterized molecular targets in NSCLC are the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK). Despite steady advances in targeted therapies within these molecular subsets, however, acquired resistance to therapy is near universal. Recent preclinical models and translational efforts have provided critical insights into the molecular mechanisms of resistance to EGFR and ALK inhibitors. In this review, we present a framework for understanding resistance to targeted therapies. We also provide overviews of the molecular mechanisms of resistance and strategies to overcome resistance among EGFR-mutant and ALK-rearranged lung cancers. To date, these strategies have centered on the development of novel next-generation inhibitors, rationale combinations, and use of local ablative therapies, such as radiotherapy.

Managing Resistance to EFGR- and ALK-Targeted Therapies

Targeted therapies have transformed the management of non-small cell lung cancer (NSCLC) and placed an increased emphasis on stratifying patients on the basis of genetic alterations in oncogenic drivers. To date, the best characterized molecular targets in NSCLC are the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK). Despite steady advances in targeted therapies within these molecular subsets, however, acquired resistance to therapy is near universal. Recent preclinical models and translational efforts have provided critical insights into the molecular mechanisms of resistance to EGFR and ALK inhibitors. In this review, we present a framework for understanding resistance to targeted therapies. We also provide overviews of the molecular mechanisms of resistance and strategies to overcome resistance among EGFR-mutant and ALK-rearranged lung cancers. To date, these strategies have centered on the development of novel next-generation inhibitors, rationale combinations, and use of local ablative therapies, such as radiotherapy.

National Trends of Local Ablative Therapy Among Young Patients With Small Renal Masses in the United States

To assess national trends in the usage of local ablative therapy for small renal masses (SRMs) in a cohort of young patients. Ablation of SRMs has been shown to offer cancer control with limited follow-up. Although ablation is considered effective for patients with limited life expectancy, its use among younger patients may be considered controversial. We used the National Cancer Data Base to identify patients between the ages of 40 and 65 years who were diagnosed with SRMs from 2004 to 2011. The primary outcome was the use of local ablative therapy. Multivariable logistic regression analysis was used to identify patient and hospital factors associated with ablation therapies in this cohort. During the study period, we identified 49,441 patients with SRMs, of which 2789 (5.6%) were treated with ablative therapies. The proportion of patients undergoing ablation gradually rose from 2.2% in 2004 to 6.2% in 2011 (P < .001). On multivariable analysis, patients were more likely to receive local ablation at academic hospitals (odds ratio [OR]: 1.5; P < .001) compared with community hospitals, or primarily insured by Medicaid (OR: 1.4; P < .001) or Medicare (OR: 1.3; P < .001) compared with private insurance. The use of local ablative therapies is gradually rising but has so far been limited to a small fraction of young patients with SRMs. Patients treated at high-volume, academic hospitals or insured with Medicaid or Medicare were treated to a greater degree with ablation. These results have important implications for the adoption of ablation and the need for long-term surveillance.

MP84-15 NATIONAL TRENDS OF LOCAL ABLATIVE THERAPY AMONG YOUNG PATIENTS WITH SMALL RENAL MASSES

You have accessJournal of UrologyKidney Cancer: Surgical Therapy VII1 Apr 2015MP84-15 NATIONAL TRENDS OF LOCAL ABLATIVE THERAPY AMONG YOUNG PATIENTS WITH SMALL RENAL MASSES Jonathan E. Kiechle, Shan Dong, Robert Abouassaly, Hui Zhu, Edward E. Cherullo, Nilay D. Shah, Dean Nakamoto, Marc C. Smaldone, Matthew M. Cooney, and Simon P. Kim Jonathan E. KiechleJonathan E. Kiechle More articles by this author , Shan DongShan Dong More articles by this author , Robert AbouassalyRobert Abouassaly More articles by this author , Hui ZhuHui Zhu More articles by this author , Edward E. CherulloEdward E. Cherullo More articles by this author , Nilay D. ShahNilay D. Shah More articles by this author , Dean NakamotoDean Nakamoto More articles by this author , Marc C. SmaldoneMarc C. Smaldone More articles by this author , Matthew M. CooneyMatthew M. Cooney More articles by this author , and Simon P. KimSimon P. Kim More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1982AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Ablation of small renal masses (SRM's) has been shown to offer cancer control with limited follow-up. However, the long-term oncologic outcome remains uncertain. Although ablation is considered effective for patients with limited life expectancy, its use among younger patients may be considered controversial with limited long-term oncologic follow-up. Therefore, we sought to assess national trends in the local ablative therapy of SRM's in young patients. METHODS We used the National Cancer Database to identify all patients between the ages of 40 to 65 years old diagnosed with clinically localized T1a (< 4 cm) renal cell carcinoma (RCC) from 2004 to 2011. The primary outcome was the use of local ablative therapy to treat T1a renal masses. Multivariable logistic regression analysis was used to identify patient and hospital factors associated with ablation therapies in this patient cohort. RESULTS During the study period, we identified 49,441 patients with clinical T1a renal masses between the ages of 40-65 of which 2,789 (5.6%) were treated with primary ablative therapies. The proportion of patients undergoing ablation rose from 2.2% in 2004 to 6.2% in 2011 (p<0.001 for trend). On multivariable analysis, patients were more likely to undergo local ablation at academic hospitals (OR: 1.5; p<0.001) compared to community hospitals. Similarly, patients primarily insured by Medicaid (OR: 1.4; p<0.001) or Medicare (OR: 1.3; p<0.001) were more likely to undergo ablation compared to those with private insurance. CONCLUSIONS Use of local ablative therapies is gradually rising, but still used in a small fraction of patients with T1a RCC. Patients treated at high volume, academic hospitals or insured with Medicaid or Medicare were treated to a greater degree with ablation. These results have important implications about the dissemination of ablation and need for long-term oncologic follow-up data. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e1064 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jonathan E. Kiechle More articles by this author Shan Dong More articles by this author Robert Abouassaly More articles by this author Hui Zhu More articles by this author Edward E. Cherullo More articles by this author Nilay D. Shah More articles by this author Dean Nakamoto More articles by this author Marc C. Smaldone More articles by this author Matthew M. Cooney More articles by this author Simon P. Kim More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...