The impact of radiosurgery fractionation and tumor radiobiology on the local control of brain metastases

2013 ◽  
Vol 119 (5) ◽  
pp. 1131-1138 ◽  
Author(s):  
Eric K. Oermann ◽  
Marie-Adele S. Kress ◽  
Jonathan V. Todd ◽  
Brian T. Collins ◽  
Riane Hoffman ◽  
...  
Keyword(s):  
Local Control ◽  
Local Tumor Control ◽  
Dose Fractionation ◽  
Tumor Control ◽  
Metastatic Tumors ◽  
Single Fraction ◽  
Frameless Radiosurgery ◽  
Whole Brain Radiation ◽  
The Impact ◽  
The Brain

Object Experience with whole-brain radiation therapy for metastatic tumors in the brain has identified a subset of tumors that exhibit decreased local control with fractionated regimens and are thus termed radioresistant. With the advent of frameless radiosurgery, fractionated radiosurgery (2–5 fractions) is being used increasingly for metastatic tumors deemed too large or too close to crucial structures to be treated in a single session. The authors retrospectively reviewed metastatic brain tumors treated at 2 centers to analyze the dependency of local control rates on tumor radiobiology and dose fractionation. Methods The medical records of 214 patients from 2 institutions with radiation-naive metastatic tumors in the brain treated with radiosurgery given either as a single dose or in 2–5 fractions were analyzed retrospectively. The authors compared the local control rates of the radiosensitive with the radioresistant tumors after either single-fraction or fractionated radiosurgery. Results There was no difference in local tumor control rates in patients receiving single-fraction radiosurgery between radioresistant and radiosensitive tumors (p = 0.69). However, after fractionated radiosurgery, treatment for radioresistant tumors failed at a higher rate than for radiosensitive tumors with an OR of 5.37 (95% CI 3.83–6.91, p = 0.032). Conclusions Single-fraction radiosurgery is equally effective in the treatment of radioresistant and radiosensitive metastatic tumors in the brain. However, fractionated stereotactic radiosurgery is less effective in radioresistant tumor subtypes. The authors recommend that radioresistant tumors be treated in a single fraction when possible and techniques for facilitating single-fraction treatment or dose escalation be considered for larger radioresistant lesions.

Local disease control after decompressive surgery and adjuvant high-dose single-fraction radiosurgery for spine metastases

2010 ◽  
Vol 13 (1) ◽  
pp. 87-93 ◽  
Author(s):  
Hugh D. Moulding ◽  
James B. Elder ◽  
Eric Lis ◽  
Dale M. Lovelock ◽  
Zhigang Zhang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Local Control ◽  
Local Tumor Control ◽  
Local Control Rate ◽  
Surgical Decompression ◽  
Local Failure ◽  
Tumor Control ◽  
High Dose ◽  
Single Fraction ◽  
Local Disease Control

Object Adjuvant radiation following epidural spinal cord decompression for tumor is a powerful tool used to achieve local disease control and preserve neurological function. To the authors' knowledge, only 1 published report addresses adjuvant stereotactic radiosurgery after this procedure, but that study used significantly lower doses than are currently prescribed. The authors review their experience using high-dose single-fraction radiosurgery as a postoperative adjuvant following surgical decompression and instrumentation to assess long-term local tumor control, morbidity, and survival. Methods A retrospective chart review identified 21 patients treated with surgical decompression and instrumentation for high-grade, epidural, spinal cord compression from tumor, followed by single-fraction high-dose spinal radiosurgery (dose range 18–24 Gy, median 24 Gy). Spinal cord dose was limited to a cord maximal dose of 14 Gy. Tumor histologies, time between surgery and radiosurgery, time to local recurrence after radiosurgery as assessed by serial MR imaging, and time to death were determined. Competing risk analysis was used to evaluate these end points. Results In this series, 20 tumors treated (95%) were considered highly radioresistant to conventional external beam radiation. The planning target volume received a high dose (24 Gy) in 16 patients (76.2%), and a low dose (18 or 21 Gy) in 5 patients (23.8%). During the study, 15 (72%) of 21 patients died, and in all cases death was due to systemic progression as opposed to local failure. The median overall survival after radiosurgery was 310 days (range 37 days to not reached). One patient (4.8%) underwent repeat surgery for local failure and 2 patients (9.5%) underwent spine surgery for other reasons. Local control was maintained after radiosurgery in 17 (81%) of 21 patients until death or most recent follow-up, with an estimated 1-year local failure risk of 9.5%. Of the failures, 3 of 4 were noted in patients receiving low-dose radiosurgery, equaling an overall failure rate of 60% (3 of 5 patients) and a 1-year local failure estimated risk of 20%. Those patients receiving adjuvant stereotactic radiosurgery with a high dose had a 93.8% overall local control rate (15 of 16 patients), with a 1-year estimated failure risk of 6.3%. Competing risk analysis showed this to be a significant difference between radiosurgical doses. One patient experienced a significant radiation-related complication; there were no wound-related issues after radiosurgery. Conclusions Spine radiosurgery after surgical decompression and instrumentation for tumor is a safe and effective technique that can achieve local tumor control until death in the vast majority of patients. In this series, those patients who received a higher radiosurgical dose had a significantly better local control rate.

scholarly journals Image-Guided Ablation for Colorectal Liver Metastasis: Principles, Current Evidence, and the Path Forward

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3926
Author(s):  
Yuan-Mao Lin ◽  
Iwan Paolucci ◽  
Kristy K. Brock ◽  
Bruno C. Odisio
Keyword(s):  
Systemic Chemotherapy ◽  
Controlled Trial ◽  
Tumor Biology ◽  
Local Tumor Control ◽  
Current Evidence ◽  
Tumor Control ◽  
Image Guided ◽  
Size Number ◽  
Vascular Structures ◽  
The Impact

Image-guided ablation can provide effective local tumor control in selected patients with CLM. A randomized controlled trial suggested that radiofrequency ablation combined with systemic chemotherapy resulted in a survival benefit for patients with unresectable CLM, compared to systemic chemotherapy alone. For small tumors, ablation with adequate margins can be considered as an alternative to resection. The improvement of ablation technologies can allow the treatment of tumors close to major vascular structures or bile ducts, on which the applicability of thermal ablation modalities is challenging. Several factors affect the outcomes of ablation, including but not limited to tumor size, number, location, minimal ablation margin, RAS mutation status, prior hepatectomy, and extrahepatic disease. Further understanding of the impact of tumor biology and advanced imaging guidance on overall patient outcomes might help to tailor its application, and improve outcomes of image-guided ablation.

Dose to neuroanatomical structures surrounding pituitary adenomas and the effect of stereotactic radiosurgery on neuroendocrine function: an international multicenter study

2021 ◽  
pp. 1-9
Author(s):  
I. Jonathan Pomeraniec ◽  
Zhiyuan Xu ◽  
Cheng-Chia Lee ◽  
Huai-Che Yang ◽  
Tomas Chytka ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Stereotactic Radiosurgery ◽  
Multicenter Study ◽  
Pituitary Adenomas ◽  
Pituitary Stalk ◽  
Tumor Control ◽  
Single Fraction ◽  
Neuroendocrine Function ◽  
Normal Pituitary Gland ◽  
The Impact

OBJECTIVE Stereotactic radiosurgery (SRS) provides a safe and effective therapeutic modality for patients with pituitary adenomas. The mechanism of delayed endocrine deficits based on targeted radiation to the hypothalamic-pituitary axis remains unclear. Radiation to normal neuroendocrine structures likely plays a role in delayed hypopituitarism after SRS. In this multicenter study by the International Radiosurgery Research Foundation (IRRF), the authors aimed to evaluate radiation tolerance of structures surrounding pituitary adenomas and identify predictors of delayed hypopituitarism after SRS for these tumors. METHODS This is a retrospective review of patients with pituitary adenomas who underwent single-fraction SRS from 1997 to 2019 at 16 institutions within the IRRF. Dosimetric point measurements of 14 predefined neuroanatomical structures along the hypothalamus, pituitary stalk, and normal pituitary gland were made. Statistical analyses were performed to determine the impact of doses to critical structures on clinical, radiographic, and endocrine outcomes. RESULTS The study cohort comprised 521 pituitary adenomas treated with SRS. Tumor control was achieved in 93.9% of patients over a median follow-up period of 60.1 months, and 22.5% of patients developed new loss of pituitary function with a median treatment volume of 3.2 cm3. Median maximal radiosurgical doses to the hypothalamus, pituitary stalk, and normal pituitary gland were 1.4, 7.2, and 11.3 Gy, respectively. Nonfunctioning adenoma status, younger age, higher margin dose, and higher doses to the pituitary stalk and normal pituitary gland were independent predictors of new or worsening hypopituitarism. Neither the dose to the hypothalamus nor the ratio between doses to the pituitary stalk and gland were significant predictors. The threshold of the median dose to the pituitary stalk for new endocrinopathy was 10.7 Gy in a single fraction (OR 1.77, 95% CI 1.17–2.68, p = 0.006). CONCLUSIONS SRS for the treatment of pituitary adenomas affords a high tumor control rate with an acceptable risk of new or worsening endocrinopathy. This evaluation of point dosimetry to adjacent neuroanatomical structures revealed that doses to the pituitary stalk, with a threshold of 10.7 Gy, and doses to the normal gland significantly increased the risk of post-SRS hypopituitarism. In patients with preserved pre-SRS neuroendocrine function, limiting the dose to the pituitary stalk and gland while still delivering an optimal dose to the tumor appears prudent.

scholarly journals Local disease control for spinal metastases following “separation surgery” and adjuvant hypofractionated or high-dose single-fraction stereotactic radiosurgery: outcome analysis in 186 patients

2013 ◽  
Vol 18 (3) ◽  
pp. 207-214 ◽  
Author(s):  
Ilya Laufer ◽  
J. Bryan Iorgulescu ◽  
Talia Chapman ◽  
Eric Lis ◽  
Weiji Shi ◽  
...  
Keyword(s):  
Low Dose ◽  
Spinal Metastases ◽  
Local Tumor Control ◽  
Surgical Decompression ◽  
Tumor Control ◽  
High Dose ◽  
Local Tumor ◽  
Single Fraction ◽  
Tumor Histology ◽  
Local Progression

Object Decompression surgery followed by adjuvant radiotherapy is an effective therapy for preservation or recovery of neurological function and achieving durable local disease control in patients suffering from metastatic epidural spinal cord compression (ESCC). The authors examine the outcomes of postoperative image-guided intensity-modulated radiation therapy delivered as single-fraction or hypofractionated stereotactic radiosurgery (SRS) for achieving long-term local tumor control. Methods A retrospective chart review identified 186 patients with ESCC from spinal metastases who were treated with surgical decompression, instrumentation, and postoperative radiation delivered as either single-fraction SRS (24 Gy) in 40 patients (21.5%), high-dose hypofractionated SRS (24–30 Gy in 3 fractions) in 37 patients (19.9%), or low-dose hypofractionated SRS (18–36 Gy in 5 or 6 fractions) in 109 patients (58.6%). The relationships between postoperative adjuvant SRS dosing and fractionation, patient characteristics, tumor histology–specific radiosensitivity, grade of ESCC, extent of surgical decompression, response to preoperative radiotherapy, and local tumor control were evaluated by competing risks analysis. Results The total cumulative incidence of local progression was 16.4% 1 year after SRS. Multivariate Gray competing risks analysis revealed a significant improvement in local control with high-dose hypofractionated SRS (4.1% cumulative incidence of local progression at 1 year, HR 0.12, p = 0.04) as compared with low-dose hypofractionated SRS (22.6% local progression at 1 year, HR 1). Although univariate analysis demonstrated a trend toward greater risk of local progression for patients in whom preoperative conventional external beam radiation therapy failed (22.2% local progression at 1 year, HR 1.96, p = 0.07) compared with patients who did not receive any preoperative radiotherapy (11.2% local progression at 1 year, HR 1), this association was not confirmed with multivariate analysis. No other variable significantly correlated with progression-free survival, including radiation sensitivity of tumor histology, grade of ESCC, extent of surgical decompression, or patient sex. Conclusions Postoperative adjuvant SRS following epidural spinal cord decompression and instrumentation is a safe and effective strategy for establishing durable local tumor control regardless of tumor histology–specific radiosensitivity. Patients who received high-dose hypofractionated SRS demonstrated 1-year local progression rates of less than 5% (95% CI 0%–12.2%), which were superior to the results of low-dose hypofractionated SRS. The local progression rate after single-fraction SRS was less than 10% (95% CI 0%–19.0%).

scholarly journals It Is Time to Reevaluate the Management of Patients With Brain Metastases

Neurosurgery ◽  
2014 ◽  
Vol 75 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Douglas Kondziolka ◽  
Steven N. Kalkanis ◽  
Minesh P. Mehta ◽  
Manmeet Ahluwalia ◽  
Jay S. Loeffler
Keyword(s):  
Brain Metastases ◽  
Cognitive Dysfunction ◽  
Clinical Care ◽  
Radiation Risk ◽  
Whole Brain Radiation ◽  
Metastatic Lesions ◽  
Response To Chemotherapy ◽  
Impact On Survival ◽  
The Impact ◽  
The Brain

Abstract There are many elements to the science that drives the clinical care of patients with brain metastases. Although part of an understanding that continues to evolve, a number of key historical misconceptions remain that commonly drive physicians' and researchers' attitudes and approaches. By understanding how these relate to current practice, we can better comprehend our available science to provide both better research and care. These past misconceptions include: Misconception 1: Once a primary cancer spreads to the brain, the histology of that primary tumor does not have much impact on response to chemotherapy, sensitivity to radiation, risk of further brain relapse, development of additional metastatic lesions, or survival. All tumor primary histologies are the same once they spread to the brain. They are the same in terms of the number of tumors, radiosensitivity, chemoresponsiveness, risk of further brain relapse, and survival. Misconception 2: The number of brain metastases matters. This number matters in terms of subsequent brain relapse, survival, and cognitive dysfunction; the precise number of metastases can also be used as a limit in determining which patients might be eligible for a particular treatment option. Misconception 3: Cancer in the brain is always a diffuse problem due to the presence of micrometastases. Misconception 4: Whole-brain radiation therapy invariably causes disabling cognitive dysfunction if a patient lives long enough. Misconception 5: Most brain metastases are symptomatic. Thus, it is not worth screening patients for brain metastases, especially because the impact on survival is minimal. The conduct and findings of past clinical research have led to conceptions that affect clinical care yet appear limiting.

Radiosurgery in patients with renal cell carcinoma metastasis to the brain: long-term outcomes and prognostic factors influencing survival and local tumor control

2003 ◽  
Vol 98 (2) ◽  
pp. 342-349 ◽  
Author(s):  
Jason P. Sheehan ◽  
Ming-Hsi Sun ◽  
Douglas Kondziolka ◽  
John Flickinger ◽  
L. Dade Lunsford
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cell Cancer ◽  
Local Tumor Control ◽  
Tumor Control ◽  
Content Type ◽  
Extracranial Disease ◽  
The Brain ◽  
Fine Print

Object. Renal cell carcinoma is a leading cause of death from cancer and its incidence is increasing. In many patients with renal cell cancer, metastasis to the brain develops at some time during the course of the disease. Corticosteroid therapy, radiotherapy, and resection have been the mainstays of treatment. Nonetheless, the median survival in patients with renal cell carcinoma metastasis is approximately 3 to 6 months. In this study the authors examined the efficacy of gamma knife surgery in treating renal cell carcinoma metastases to the brain and evaluated factors affecting long-term survival. Methods. The authors conducted a retrospective review of 69 patients undergoing stereotactic radiosurgery for a total of 146 renal cell cancer metastases. Clinical and radiographic data encompassing a 14-year treatment interval were collected. Multivariate analyses were used to determine significant prognostic factors influencing survival. The overall median length of survival was 15 months (range 1–65 months) from the diagnosis of brain metastasis. After radiosurgery, the median survival was 13 months in patients without and 5 months in those with active extracranial disease. In a multivariate analysis, factors significantly affecting the rate of survival included the following: 1) younger patient age (p = 0.0076); 2) preoperative Karnofsky Performance Scale score (p = 0.0012); 3) time from initial cancer diagnosis to brain metastasis diagnosis (p = 0.0017); 4) treatment dose to the tumor margin (p = 0.0252); 5) maximal treatment dose (p = 0.0127); and 6) treatment isodose (p = 0.0354). Prior tumor resection, chemotherapy, immunotherapy, or whole-brain radiation therapy did not correlate with extended survival. Postradiosurgical imaging of the brain demonstrated that 63% of the metastases had decreased, 33% remained stable, and 4% eventually increased in size. Two patients (2.9%) later underwent a craniotomy and resection for a tumor refractory to radiosurgery or a new symptomatic metastasis. Eighty-three percent of patients died of progression of extracranial disease. Conclusions. Stereotactic radiosurgery for treatment of renal cell carcinoma metastases to the brain provides effective local tumor control in approximately 96% of patients and a median length of survival of 15 months. Early detection of brain metastases, aggressive treatment of systemic disease, and a therapeutic strategy including radiosurgery can offer patients an extended survival.

Single-fraction radiosurgery for the treatment of renal tumors in singular renal units.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 368-368
Author(s):  
M. D. Staehler ◽  
P. Nuhn ◽  
A. Karl ◽  
M. Bader ◽  
C. Stief ◽  
...  
Keyword(s):  
Radiation Treatment ◽  
Eastern Cooperative Oncology Group ◽  
Skin Toxicity ◽  
Local Tumor Control ◽  
Renal Tumors ◽  
Tumor Control ◽  
High Dose ◽  
Local Tumor ◽  
Single Fraction ◽  
Oncological Treatment

368 Background: High-dose local radiation treatment (stereotactic radiosurgery [SRS]) was added for selected patients to improve local control and overall survival in metastases. We report on toxicity and local tumor control in patients with renal tumors who were treated with aggressive local irradiation using a single fraction SRS with the Cyberknife in singular renal units to avoid hemodialysis. Methods: n=18 patients with renal tumors and an eastern cooperative oncology group (ECOG) status of 0 or 1 were treated with SRS. Patients with surgically removable renal lesions were not included. Prior to SRS gold markers were planted into the renal parenchyma under ultrasonographic guidance. Results: Nine patients had transitional carcinoma of the renal pelvis, six patients had renal cell carcinoma and three had other tumor entities. No skin toxicity occurred after SRS, and SRS did not induce other side effects. Local tumor control 9 months after SRS was 98% (95% CI: 89-99%). There were no treatment related deaths, and late complications after SRS were not noted so far. Renal function so far remained stable without a change in serum creatinine. Conclusions: SRS for selected patients with renal tumors is safe and effective. Single-fraction delivery as an outpatient procedure allows for convenient integration of SRS into various oncological treatment concepts. Further studies are needed to determine the limits of SRS in this setting. No significant financial relationships to disclose.

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