M. Yondorf

Phase I/II study of resection and intraoperative cesium-131 radioisotope brachytherapy in patients with newly diagnosed brain metastases.

OBJECT Resected brain metastases have a high rate of local recurrence without adjuvant therapy. Adjuvant whole-brain radiotherapy (WBRT) remains the standard of care with a local control rate > 90%. However, WBRT is delivered over 10-15 days, which can delay other therapy and is associated with acute and long-term toxicities. Permanent cesium-131 ((131)Cs) implants can be used at the time of metastatic resection, thereby avoiding the need for any additional therapy. The authors evaluated the safety, feasibility, and efficacy of a novel therapeutic approach with permanent (131)Cs brachytherapy at the resection for brain metastases. METHODS After institutional review board approval was obtained, 24 patients with a newly diagnosed metastasis to the brain were accrued to a prospective protocol between 2010 and 2012. There were 10 frontal, 7 parietal, 4 cerebellar, 2 occipital, and 1 temporal metastases. Histology included lung cancer (16), breast cancer (2), kidney cancer (2), melanoma (2), colon cancer (1), and cervical cancer (1). Stranded (131)Cs seeds were placed as permanent volume implants. The prescription dose was 80 Gy at a 5-mm depth from the resection cavity surface. Distant metastases were treated with stereotactic radiosurgery (SRS) or WBRT, depending on the number of lesions. The primary end point was local (resection cavity) freedom from progression (FFP). Secondary end points included regional FFP, distant FFP, median survival, overall survival (OS), and toxicity. RESULTS The median follow-up was 19.3 months (range 12.89-29.57 months). The median age was 65 years (range 45-84 years). The median size of resected tumor was 2.7 cm (range 1.5-5.5 cm), and the median volume of resected tumor was 10.31 cm(3) (range 1.77-87.11 cm(3)). The median number of seeds used was 12 (range 4-35), with a median activity of 3.82 mCi per seed (range 3.31-4.83 mCi) and total activity of 46.91 mCi (range 15.31-130.70 mCi). Local FFP was 100%. There was 1 adjacent leptomeningeal recurrence, resulting in a 1-year regional FFP of 93.8% (95% CI 63.2%-99.1%). One-year distant FFP was 48.4% (95% CI 26.3%-67.4%). Median OS was 9.9 months (95% CI 4.8 months, upper limit not estimated) and 1-year OS was 50.0% (95% CI 29.1%-67.8%). Complications included CSF leak (1), seizure (1), and infection (1). There was no radiation necrosis. CONCLUSIONS The use of postresection permanent (131)Cs brachytherapy implants resulted in no local recurrences and no radiation necrosis. This treatment was safe, well tolerated, and convenient for patients, resulting in a short radiation treatment course, high response rate, and minimal toxicity. These findings merit further study with a multicenter trial.

Administration of concurrent vaginal brachytherapy during chemotherapy for treatment of endometrial cancer.

PURPOSE To evaluate the tolerability and toxicity of administering vaginal brachytherapy (VB) concurrently during chemotherapy compared with the sequential approach for patients with endometrial cancer. METHODS AND MATERIALS A retrospective analysis of 372 surgically staged patients with endometrial cancer American Joint Committee on Cancer 2009 stages I to IV treated with adjuvant postoperative radiation therapy (RT) at our institution from 2001 to 2012 was conducted. All patients received VB+external beam RT (EBRT)+6 cycles of adjuvant carboplatin- and paclitaxel-based chemotherapy. The VB mean dose was 15.08 Gy (range, 15-20 Gy), with 3 to 4 weekly applications, and the EBRT mean dose was 45 Gy delivered with 3-dimensional or intensity modulated RT techniques. Hematologic, gastrointestinal (GI), and genitourinary (GU) toxicities were assessed by Common Toxicity Criteria (CTC) and compared between sequential and concurrent chemotherapy and VB schedules. RESULTS Among patients who received RT and adjuvant chemotherapy, 180 of 372 patients (48%) received RT sandwiched between cycles 3 and 4 of chemotherapy. A separate group of 192 patients (52%) were treated with VB during the first 3 cycles of chemotherapy, with a weekly application on nonchemotherapy days, and received the EBRT portion in a sandwiched fashion. Patients treated with VB during chemotherapy had a decreased overall treatment time by 4 weeks (P<.001; 95% confidence interval: 3.99-4.02) and sustained no difference in CTC-graded acute hematologic, GI, or GU toxicities in comparison with the patients treated with VB and chemotherapy in a sequential manner (P>.05). CTC grade 3 or 4 hematologic, GI, and GU toxicities were zero. CONCLUSIONS VB during chemotherapy is well tolerated, decreases overall treatment time, and does not render more toxicity than the sequential regimen.

Surgical Technique and Clinically Relevant Resection Cavity Dynamics Following Implantation of Cesium-131 Brachytherapy in Patients With Brain Metastases

BACKGROUND: Cesium-131 (Cs-131) brachytherapy is used to reduce local recurrence of resected brain metastases. To ensure dose homogeneity and reduce risk of radiation necrosis, interseed distance and cavity volume must remain stable during delivery. OBJECTIVE: To investigate the efficacy of the “seeds-on-a-string” technique with intracavitary fibrin glue in achieving cavity volume stability. METHODS: We placed intraoperative Cs-131 brachytherapy in 30 cavities postresection of brain metastases. Seeds-on-a-string were placed like barrel staves within the cavity with fibrin glue. Serial magnetic resonance imaging occurred postoperatively. Preoperative tumor volumes were compared with postoperative cavity volumes to evaluate volume stability. Thirty patients who underwent postresective stereotactic radiosurgery (SRS) were used as a control group for volumetric comparison. RESULTS: Cs-131 and SRS patients exhibited consistent cavity shrinkage over the median 110-day follow-up (P < .001), with total median shrinkage of 56.5% (Cs-131) and 84.8% (SRS). During the first month when ≈88% of Cs-131 dosage is delivered, however, there was nonsignificant volume decrease in the Cs-131 group (median 22.0%; P = .06), whereas SRS patients showed significantly more shrinkage (46.7%; P = .042). No events of radiation necrosis occurred in either group. CONCLUSION: Cs-131 patients exhibited significantly less cavity shrinkage than SRS patients during the first critical month with 88% Cs-131 dose delivery. This significant difference in shrinkage suggests that the intracavitary seeds-on-a-string technique facilitates increased cavity stability, promoting more homogenous dose delivery. ABBREVIATIONS: Cs-131, Cesium-131 FLAIR, fluid-attenuated inversion recovery I-125, Iodine-125 SRS, stereotactic radiosurgery WBRT, whole brain radiotherapy

Phase I/II Study of Neurosurgical Resection and Intra-operative Cesium-131 Radio-isotope Brachytherapy in Patients with Newly Diagnosed Brain Metastases

OBJECT Resected brain metastases have a high rate of local recurrence without adjuvant therapy. Adjuvant whole-brain radiotherapy (WBRT) remains the standard of care with a local control rate > 90%. However, WBRT is delivered over 10-15 days, which can delay other therapy and is associated with acute and long-term toxicities. Permanent cesium-131 ((131)Cs) implants can be used at the time of metastatic resection, thereby avoiding the need for any additional therapy. The authors evaluated the safety, feasibility, and efficacy of a novel therapeutic approach with permanent (131)Cs brachytherapy at the resection for brain metastases. METHODS After institutional review board approval was obtained, 24 patients with a newly diagnosed metastasis to the brain were accrued to a prospective protocol between 2010 and 2012. There were 10 frontal, 7 parietal, 4 cerebellar, 2 occipital, and 1 temporal metastases. Histology included lung cancer (16), breast cancer (2), kidney cancer (2), melanoma (2), colon cancer (1), and cervical cancer (1). Stranded (131)Cs seeds were placed as permanent volume implants. The prescription dose was 80 Gy at a 5-mm depth from the resection cavity surface. Distant metastases were treated with stereotactic radiosurgery (SRS) or WBRT, depending on the number of lesions. The primary end point was local (resection cavity) freedom from progression (FFP). Secondary end points included regional FFP, distant FFP, median survival, overall survival (OS), and toxicity. RESULTS The median follow-up was 19.3 months (range 12.89-29.57 months). The median age was 65 years (range 45-84 years). The median size of resected tumor was 2.7 cm (range 1.5-5.5 cm), and the median volume of resected tumor was 10.31 cm(3) (range 1.77-87.11 cm(3)). The median number of seeds used was 12 (range 4-35), with a median activity of 3.82 mCi per seed (range 3.31-4.83 mCi) and total activity of 46.91 mCi (range 15.31-130.70 mCi). Local FFP was 100%. There was 1 adjacent leptomeningeal recurrence, resulting in a 1-year regional FFP of 93.8% (95% CI 63.2%-99.1%). One-year distant FFP was 48.4% (95% CI 26.3%-67.4%). Median OS was 9.9 months (95% CI 4.8 months, upper limit not estimated) and 1-year OS was 50.0% (95% CI 29.1%-67.8%). Complications included CSF leak (1), seizure (1), and infection (1). There was no radiation necrosis. CONCLUSIONS The use of postresection permanent (131)Cs brachytherapy implants resulted in no local recurrences and no radiation necrosis. This treatment was safe, well tolerated, and convenient for patients, resulting in a short radiation treatment course, high response rate, and minimal toxicity. These findings merit further study with a multicenter trial.

Radiation Exposure and Safety Precautions Following 131Cs Brachytherapy in Patients with Brain Tumors

Abstract Cesium‐131 (131Cs) brachytherapy is a safe and convenient treatment option for patients with resected brain tumors. This study prospectively analyzes radiation exposure in the patient population who were treated with a maximally safe neurosurgical resection and 131Cs brachytherapy. Following implantation, radiation dose rate measurements were taken at the surface, 35 cm, and 100 cm distances. Using the half-life of 131Cs (9.69 d), the dose rates were extrapolated at these distances over a period of time (t = 30 d). Data from dosimetry badges and rings worn by surgeons and radiation oncologists were collected and analyzed. Postoperatively, median dose rate was 0.2475 mSv h−1, 0.01 mSv h−1, and 0.001 mSv h−1 and at 30 d post-implant, 0.0298 mSv h−1, 0.0012 mSv h−1, and 0.0001 mSv h−1 at the surface, 35 cm, and 100 cm, respectively. All but one badge and ring measured a dose equivalent corresponding to ~0 mSv h−1, while 1 badge measured 0.02/0.02/0.02 mSv h−1. There was a significant correlation between the number of seeds implanted and dose rate at the surface (p = 0.0169). When stratified by the number of seeds: 4–15 seeds (n = 14) and 20–50 seeds (n = 4) had median dose rates of 0.1475 mSv h−1 and 0.5565 mSv h−1, respectively (p = 0.0015). Using National Council on Radiation Protection guidelines, this study shows that dose equivalent from permanent 131Cs brachytherapy for the treatment of brain tumors is limited, and it maintains safe levels of exposure to family and medical personnel. Such information is critical knowledge for the neurosurgeons, radiation oncologists, nurses, hospital staff, and family as this method is gaining nationwide popularity.

Phase I/II study of resection and intraoperative cesium-131 radioisotope brachytherapy in patients with newly diagnosed brain metastases: Clinical article

OBJECT Resected brain metastases have a high rate of local recurrence without adjuvant therapy. Adjuvant whole-brain radiotherapy (WBRT) remains the standard of care with a local control rate > 90%. However, WBRT is delivered over 10-15 days, which can delay other therapy and is associated with acute and long-term toxicities. Permanent cesium-131 ((131)Cs) implants can be used at the time of metastatic resection, thereby avoiding the need for any additional therapy. The authors evaluated the safety, feasibility, and efficacy of a novel therapeutic approach with permanent (131)Cs brachytherapy at the resection for brain metastases. METHODS After institutional review board approval was obtained, 24 patients with a newly diagnosed metastasis to the brain were accrued to a prospective protocol between 2010 and 2012. There were 10 frontal, 7 parietal, 4 cerebellar, 2 occipital, and 1 temporal metastases. Histology included lung cancer (16), breast cancer (2), kidney cancer (2), melanoma (2), colon cancer (1), and cervical cancer (1). Stranded (131)Cs seeds were placed as permanent volume implants. The prescription dose was 80 Gy at a 5-mm depth from the resection cavity surface. Distant metastases were treated with stereotactic radiosurgery (SRS) or WBRT, depending on the number of lesions. The primary end point was local (resection cavity) freedom from progression (FFP). Secondary end points included regional FFP, distant FFP, median survival, overall survival (OS), and toxicity. RESULTS The median follow-up was 19.3 months (range 12.89-29.57 months). The median age was 65 years (range 45-84 years). The median size of resected tumor was 2.7 cm (range 1.5-5.5 cm), and the median volume of resected tumor was 10.31 cm(3) (range 1.77-87.11 cm(3)). The median number of seeds used was 12 (range 4-35), with a median activity of 3.82 mCi per seed (range 3.31-4.83 mCi) and total activity of 46.91 mCi (range 15.31-130.70 mCi). Local FFP was 100%. There was 1 adjacent leptomeningeal recurrence, resulting in a 1-year regional FFP of 93.8% (95% CI 63.2%-99.1%). One-year distant FFP was 48.4% (95% CI 26.3%-67.4%). Median OS was 9.9 months (95% CI 4.8 months, upper limit not estimated) and 1-year OS was 50.0% (95% CI 29.1%-67.8%). Complications included CSF leak (1), seizure (1), and infection (1). There was no radiation necrosis. CONCLUSIONS The use of postresection permanent (131)Cs brachytherapy implants resulted in no local recurrences and no radiation necrosis. This treatment was safe, well tolerated, and convenient for patients, resulting in a short radiation treatment course, high response rate, and minimal toxicity. These findings merit further study with a multicenter trial.

SU‐E‐T‐259: Dosimetric Comparison of Cs‐131 Vs. I‐125 Vs. Pd‐103 Intraoperative Brachytherapy in Patients with Resected Brain Metastasis

Purpose: Cs‐131, I‐125 and Pd‐103, have been used for permanent implant brachytherapy. Cs‐131 has shorter half‐life — 9.7 days as compared to I‐125 and Pd‐103 — 59.4 and 17.0 days, respectively. It is likely more biologically efficient for tumor cell kill as the initial dose rate from Cs‐131(23.9 cGy/h) is 4 times higher than that of I‐125(5.8 cGy/h) and twice of Pd‐103(13.62 cGy/h). These isotopes differ in their average gamma‐ray energies (30.4keV, 28.5keV and 20.8keV, respectively). This study examines the dosimetric differences amongst these isotopes when used as a permanent implant for patients with resected brain metastasis with regard to exposure of normal brain tissue and the potential for developing radiation necrosis (RN). Methods: 24 patients with a single newly diagnosed and resected brain metastasis were implanted with Cs‐131. Post‐op dosimetry plans were generated for Cs‐131, I‐125 model #6711 and Pd‐103 model #200. The prescription dose was 80 Gy to 5mm depth from the surface cavity. The mean air kerma strength for the Cs‐131, I‐125 and Pd‐103 seeds were 2.4U, 0.6985U and 2.11U respectively. The volume of brain tissue exposed to radiation at 100%, 80% and 50% isodose lines were compared for each isotope. Results: Significantly larger volume of brain tissue exposed to radiation, with the use of I‐125 when compared to both Cs‐131 (p less than 0.00005) and Pd‐103 (p less than 0.00004). There is no significant difference when comparing Cs‐131 to Pd‐103 (p=0.26605). Conclusion: In this analysis, we report that Cs‐131 and Pd‐103 expose less normal brain tissue to radiation when compared to I‐125, thus providing a dosimetric superiority and subjecting less tissue to RN. In addition, Cs‐131 has the shortest T1/2 and in our trial with a median follow up of 10 months, all 24 patients have 100% local control while experiencing 0% incidence of RN.

Phase I/II Study of Neurosurgical Resection and Intraoperative Cesium-131 Radio-isotope Brachytherapy in Patients With Newly Diagnosed Brain Metastases

Object—Resected brain metastases have a high rate of local recurrence without adjuvant therapy. Adjuvant whole brain radiotherapy (WBRT) remains the standard of care with the rate of local control >90%. However, WBRT is delivered over 10–15 days, which can delay other therapy and is associated with acute and long-term toxicities. Intra-operative permanent Cesium-131 (Cs-131) implants can be performed at the time of surgery, thereby avoiding any additional therapy. We evaluate the safety, feasibility and efficacy of a novel treatment approach of brain metastases with a permanent intra-operative Cs-131 brachytherapy. Methods—After IRB approval, 24 patients with a newly diagnosed metastasis to the brain (n=24) were accrued on a prospective protocol between 2010 and 2012. There were 10 frontal, 7 parietal, 4 cerebellar, 2 occipital, and 1 temporal metastases. Histology included lung (16), breast (2), kidney (2), melanoma (2), colon (1), and cervix (1). Cs-131 stranded seeds were placed as a permanent volume implant. Prescription dose was 80Gy at 5mm depth from the resection cavity surface. Distant metastases were treated with stereotactic radiosurgery (SRS) or WBRT, depending on the number of lesions. Primary end point was resection cavity freedom from progression (FFP). Secondary end points included distant metastases FFP, median survival, overall survival (OS), and toxicity. Correspondence to: A.Gabriella Wernicke, M.D., M.Sc, Weill Medical College of Cornell University, Stich Radiation Oncology, 525 East 68th Street, New York, New York 10065, Telephone: (212) 746-3641, Facsimile: (212) 746-8749, gaw9008@med.cornell.edu. Portions of this work were presented as an oral presentation at ASTRO’s 54th Annual Meeting, Boston, MA, October 28–31, 2012 Disclosure: All the authors declare that they have no personal financial or institutional conflict of interest in any of the materials discussed in this article. NIH Public Access Author Manuscript J Neurosurg. Author manuscript; available in PMC 2015 August 01. Published in final edited form as: J Neurosurg. 2014 August ; 121(2): 338–348. doi:10.3171/2014.3.JNS131140. N IH -P A A uhor M anscript N IH -P A A uhor M anscript N IH -P A A uhor M anscript Results—Median follow-up was 19.3 months (range, 12.89 – 29.57 months). Median age was 65 years (range, 45–84 years). Median volume of resected tumor was 10.31 cc (range, 1.77 87.11 cc). Median number of seeds employed was 12 (range, 4–35) with median activity per seed of 3.82 mCi (range, 3.31–4.83 mCi) and total activity of 46.91 mCi (range, 15.31–130.70 mCi). Local recurrence FFP was 100%. There was 1 adjacent leptomeningeal recurrence, resulting in a 1-year regional FFP of 93.8% (95% CI = 63.2%, 99.1%). Distant metastasis FFP was 48.4% (95% CI = 26.3%, 67.4%). Median OS was 9.9 months (95% CI = 4.8 months, upper limit not estimated) and 1-year OS was 50.0% (95% CI = 29.1%, 67.8%). Complications included cerebrospinal fluid leak (1), seizure (1), infection (1). There was no radiation necrosis. Conclusions—Cs-131 post-resection permanent brachytherapy implants resulted in no local recurrences and no radiation necrosis. This treatment approach was safe, well tolerated, and convenient for patients, resulting in a short radiation treatment course, high response rates, and minimal toxicity. These results merit further study with a multicenter trial.