High Local Control Rates Research Articles

Phase II trial of neoadjuvant chemohormonal therapy (NAC) in prostate cancer (PC) with response assessment using PSMA PET/MRI.

334 Background: Previous studies have shown that addition of docetaxel to androgen deprivation therapy (ADT) significantly improves progression-free survival (PFS) and overall survival (OS) in men with metastatic hormone-sensitive PC. Removal of the primary may also improve outcomes by reducing tumor self-seeding. We are conducting a phase II trial in men with PC to examine the feasibility of NAC, response using PSMA PET/MRI imaging and molecular mechanisms of resistance. Methods: This is an open-label, single-arm trial. Thirty patients with newly diagnosed very high risk localized, locally advanced or oligometastatic PC will receive ADT/docetaxel for three cycles before prostatectomy. The primary endpoint is rate of complete pathologic response. Key secondary objectives include PSA recurrence at month 12 after surgery. Exploratory objectives include tumor response and response heterogeneity in primary and metastatic tumors before and after treatment assessed by PSMA PET/MRI and evaluation of gene expression signatures in cancer cells, prostate stroma, bone marrow microenvironment and circulating tumor cells. Results: To date, 26 of 30 patients have enrolled and completed treatment. Mean age was 61 and mean PSA at time of diagnosis was 32.1 ng/dl. All patients had multi-focal prostate cancer with 23/26 patients with Gleason Grade Group 5. Metastatic disease by conventional imaging was identified in 6/26 patients (5 in lymph nodes [LN] and bone, 1 in LN only). Treatment was overall well tolerated. All patients had multi-focal primary prostate cancer detected on PSMA PET/MRI. All patients had a decline in PSMA PET SUVmax in at least one intraprostatic lesion. Two patients had an increase in SUVmax in at least one intraprostatic lesion that correlated with a resistant tumor focus on histopathology. Conclusions: NAC prior to surgery generates high rates of local tumor control with a heterogeneous response between foci. Primary resistance, identified by increasing PSMA PET SUVmax, is uncommon, however incomplete responses were observed in nearly all patients, suggesting that more cycles of treatment would improve response. PSMA PET/MRI can be used to monitor response and resistance in PC. Clinical trial information: NCT03358563.

Clinical outcomes of stereotactic body radiation therapy for small hepatocellular carcinoma.

The purpose of this study was to investigate the long-term oncologic outcomes after stereotactic body radiation therapy (SBRT) for small hepatocellular carcinoma (HCC). A total of 290 patients with HCC were registered between March 2007 and July 2013. A dose of 10-15Gy per fraction was given over three to four consecutive days, resulting in a total dose of 30-60Gy. Overall and recurrence-free survivals were estimated from the date of the start of SBRT to the date of death, the last follow-up examination, or to the date of tumor recurrence. The median follow-up period of all patients was 38.2months, and the median tumor size was 1.7cm. Overall survival (OS) rate at 5years was 44.9%. Multivariate analyses revealed that age, Child-Pugh class, tumor size, and albumin levels were significant factors for OS. The 5-year local control rate was 91.3%. In multivariate analysis, tumor size and albumin were significantly associated with local tumor control. However, there was a negative correlation between total dose and tumor size in Pearson's correlation analysis (r=-0.111, P=0.046). Stereotactic body radiation therapy was an excellent ablative treatment option for patients with small HCC. Tumor size was a significant factor for local tumor control after SBRT, although the total dose was negatively correlated with tumor size. Considering the low OS rates and the high local tumor control rates, the combined SBRT and systemic therapies may be beneficial for improving survival outcomes.

Recursive partitioning model-based analysis for survival of colorectal cancer patients with lung and liver oligometastases treated with stereotactic body radiation therapy.

Liver and lung are common sites of metastases from colorectal cancer (CRC). Stereotactic body radiation therapy (SBRT) represents a valid treatment, with high rates of local control (LC). In this study, we applied recursive partitioning model-based analysis (RPA) to define class risks for overall survival (OS) and progression free survival (PFS) in oligometastatic CRC patients. In this monocentric analysis, we included patients with lung or liver metastases. Patients were candidate to SBRT if a maximum of 5 metastases. End points of the present analysis were LC, PFS, and OS. The binary classification tree approach with RPA was applied to stratify the patients into risk groups based on OS and PFS. 218 patients were treated with SBRT on 371 metastases. Majority of patients (56%) was treated on single lesion, followed by 2 (26.1%) and 3 lesions (14.7%). Median follow-up was 22.7months. Rates of LC were 84.2% at 1year and 73.8% at 3years. Rates of PFS at 1 and 3years were 42.2% and 14.9%, respectively. RPA identified 3 classes for PFS, according to age and number of metastases with 3-year PFS of 30.6%, 13.5% and 8.4%. Overall survival was 87.2% at 1year, 51.9% at 3years, and 36.8% at 5years. RPA identified 3 nodes. Class 1 included patients with liver metastases (3-year OS 35.2%). Class 2 included patients with lung metastases and DFI ≤ 48months (3-year OS 65%). Class 3 included patients with lung metastases and DFI > 48months (3-year OS 73.5%). Stereotactic body radiation therapy can be considered an effective treatment for the management of liver and lung metastases from CRC. With RPA, we identified prognostic risk class to define patients who could benefit the most from SBRT.

Upfront radiotherapy with brachytherapy for medically inoperable and unresectable patients with high-risk endometrial cancer

ObjectivesComprehensive surgery with adjuvant therapy is standard of care for high-risk endometrial cancers, whereas upfront radiotherapy with brachytherapy is indicated for inoperable/unresectable patients, irrespective of risk. We evaluated outcomes for inoperable/unresectable patients with high-risk endometrial cancer (HREC: stage III and/or grade 3) and low-risk endometrial cancer (LREC: stage I/II and grade 1/2) treated with upfront radiotherapy. MethodsTwenty-nine patients with inoperable/unresectable endometrial cancer were treated with upfront radiotherapy at an academic medical center from 2012 to 2019. Cancer-specific survival (CSS), overall survival (OS), and recurrence rates between patients with HREC and LREC were compared. ResultsMedian follow-up was 17.0 months (range 3.7–54.0). Twenty cancers were stage I + II and nine were stage III. Twenty-one cancers were grade 1 + 2 and eight were grade 3. Thirteen patients (45%) had HREC. Twenty-five patients received radiotherapy/chemoradiotherapy for primary treatment, while 4 patients received chemoradiotherapy before surgery. All patients underwent high dose rate brachytherapy (HDR) with 7 receiving HDR alone and 22 receiving external beam radiation and HDR. Two-year CSS was 100% for both HREC and LREC patients (log-rank p = 0.32). There was no OS difference between HREC and LREC patients (2-year: 73% vs. 77%; log-rank p = 0.33). Four HREC and 1 LREC patients recurred with one local recurrence in each group. There were no acute grade ≥3 and two late grade ≥3 gastrointestinal/genitourinary toxicities. ConclusionsUpfront radiotherapy for inoperable/unresectable HREC patients was well tolerated with high local control and CSS rates. Upfront radiotherapy with brachytherapy remains important even for high-risk inoperable and unresectable endometrial cancer patients.

Flattening filter free VMAT for a stereotactic, single-dose of 30 Gy to lung lesion in a 15-min treatment slot.

Cone‐beam CT‐guided single dose of lung stereotactic body radiotherapy (SBRT) treatment with a flattening filter free (FFF) beam and volumetric modulated arc therapy (VMAT) is a safe and highly effective treatment modality for selective small lung lesions. Four‐dimensional (4D) CT‐based treatment plans were generated using advanced AcurosXB algorithm for heterogeneity corrections. 6X‐FFF beam produced highly conformal radiosurgical dose distribution to the target and reduced lung SBRT fraction duration to less than 10 min for a single dose of 30 Gy, significantly improving patient comfort and clinic workflow. Early follow‐up CT imaging results (mean, 8 months) show high local control rates (100%) with no acute lung or rib toxicity. Longer clinical follow‐up in a larger patient cohort managed in this fashion is underway to further validate this treatment approach.

Intensity-modulated proton therapy using dose-painting pencil beam scanning for high-risk hepatocellular carcinoma.

558 Background: High rates of local control are achievable with hypofractionated proton therapy with passive techniques for hepatocellular carcinoma (HCC), but may have limitations when tumors are adjacent to organs-at-risk (OARs), which may result in tumor underdosage and lead to inferior local control. We present the first reported series of HCC patients treated with pencil beam scanning (PBS) intensity-modulated proton therapy (IMPT) using a simultaneous-integrated boost and protection (SIB/SIP) technique to escalate tumor dose while protecting adjacent OARs. Methods: Twenty-five HCC patients were treated between 2015-2019 with a 15-fraction regimen using IMPT SIB/SIP. SIB/SIP dose levels generally ranged from 36.0-67.5 GyRBE to minimize dose to OARs at their respective dose-limiting thresholds (e.g. luminal gastrointestinal organs, chest wall). Radiation-induced liver disease (RILD) was defined by a Child-Pugh (CP) score increase of 2 or greater and/or any RTOG grade 3 enzyme elevation. Other toxicities were graded by CTCAEv5.0. Overall survival (OS), progression-free survival (PFS), and local control were calculated using the Kaplan-Meier method. Results: Patients most commonly had BCLC stage B or C disease (84%) and CP-A (80%) and ALBI grade 2 (60%) liver function. Median gross tumor volume (GTV) size and volume were 12.3 cm (range 2.17-20.57) and 461 cc (range 4.68-2439), and 32% had gross vascular invasion. Median mean and minimum dose delivered to the gross tumor volume (GTV) was 64.0 GyRBE (EQD2 76.1, BED 91.3, range 54.3-69.6) and 45.1 GyRBE (EQD2 48.9, BED 58.7, range 33.4-67.7), respectively. Median mean dose to liver minus GTV was 15.0 GyRBE (range, 8.2-19.6). 1-year OS, PFS, and local control were 66%, 32%, and 84%, respectively. No isolated local failures occurred. Two patients experienced RILD with no RILD-related deaths. Two grade 3 non-GI toxicities occurred: 1 rib fracture and 1 pneumonitis. No acute or late GI grade ≥2 occurred. Conclusions: In our series of HCC patients with large tumors near OARs, IMPT SIB/SIP allows for tumor dose escalation while sparing of OARs and results in favorable local control and acceptable toxicities.

Local Control and Toxicity of Multilevel Spine Stereotactic Body Radiotherapy.

Spine stereotactic body radiotherapy (sSBRT) is commonly limited to 1 or 2 vertebral levels given a paucity of efficacy and toxicity data when more than 2 levels are treated. To prove our hypothesis that multilevel sSBRT could provide similar rates of local control (LC) (primary endpoint) and toxicity as single-level treatment using the same clinical target, planning target, and planning organ-at-risk volumes. We analyzed consecutive cases of sSBRT treated from 2013 to 2017. Time-to-event outcomes for single-level and multilevel cases were compared using mixed effect Cox models and differences in toxicity rates were evaluated using linear mixed effect models. All models incorporate a patient-level random intercept to account for any within-patient correlation across cases. There were 101 single-level and 84 multilevel sSBRT cases (2-7 continuous vertebral levels). One-year LC was 95% vs 85%, respectively. After adjusting for baseline covariates, dose delivered, and accounting for within-patient correlation, there was no significant difference in time to local failure (hazard ratio, HR 1.79 [0.59-5.4]; P=.30). Pain improved in 83.5% of the 139 initially symptomatic tumors. There were no significant differences in grade 2+acute or late toxicities between single-level and multilevel sSBRT. With rigorous patient immobilization, quality assurance, and image guidance, multilevel sSBRT provides high rates of LC, similar to single-level treatment, without need for larger planning volume margins. Efforts to improve prognostication and case selection for multilevel sSBRT are warranted to ensure that the benefits of improved LC over palliative radiation are justified.

Monocentric experiences of stereotactic body radiation therapy (SBRT) for advanced hepatocellular carcinomas (BCLC-C)

Hepatocellular carcinomas (HCCs) are highly malignant primary liver cancers with poor prognosis and limited treatment options in advanced stages of disease. Treatment of HCC requires interdisciplinary discussion and multimodal therapy approaches. Beside established loco-regional and systemic therapies, stereotactic body radiation therapy (SBRT) gained increasing importance over recent years. First results of early clinical studies indicate high rates of local control with a good safety profile. In the present work, we evaluated our single center experiences with SBRT in patients with advanced HCCs.Ten patients with 16 SBRTs were included and retrospectively analyzed in this case collection. All patients presented in advanced tumor stages with vascular invasion and/or metastases, but preserved liver function. Two patients were treated only with SBRT, two after TACE and six patients received SBRT in addition to systemic therapy. In most of the cases SBRT were applied to intrahepatic lesions. Large tumor thromboses, lymph nodes as well as bone metastases were irradiated in one, three and five fractions with a median overall dose of 38 Gy. We observed a good local tumor control with a good safety profile in all cases. No severe complications occurred in combination to sequential as well as additive approach to loco-regional or systemic treatments.In conclusion, our experiences confirm results of early clinical studies indicating safe use and good local control rates also in advanced stages of HCC with preserved liver function.

Does Baking Soda Function as a Magic Bullet for Patients With Cancer? A Mini Review.

Sodium bicarbonate, commonly known as baking soda, is widely used in the clinic as an antacid for treating gastric hyperacidity, among other conditions. Chao et al have reported a clinical trial about targeting intratumor lactic acidosis–transarterial chemoembolization. Based on conventional transarterial chemoembolization, the authors added a 5% sodium bicarbonate solution to cytotoxic drugs, resulting in a high local control rate. The explanation for the antitumor effects of sodium bicarbonate is related to acidosis in the tumor microenvironment. In this review, we summarize the findings from studies administering sodium bicarbonate alone or in combination with other anticancer therapies as cancer treatments, and discuss methods for safe and effective use of sodium bicarbonate in the clinic.

Safety and efficacy analysis of microwave ablation in small hepatocellular carcinomas sized below 3 cm

PurposeThe aim of this study was to investigate the efficacy and safety of microwave ablation (MWA) in small hepatocellular carcinomas sized ≤ 3 cm, determine long-term survival, and identify prognostic factors for survival rates.Material and methodsIn this study, the radiological and laboratory findings obtained from 31 consecutive patients who underwent MWA were retrospectively evaluated. The survival periods and complication rates were analysed.ResultsMicrowave ablation was applied to 42 hepatocellular carcinoma nodules in 31 patients. The mean age of the patients was 61 ± 7.3 (median 62, range 46-78) years. The mean overall survival (OS) was 47.4 ± 3.3 months. The rates of cumulative OS in the first, second, and third years were 95.2%, 91.8%, and 79.2%, respectively. The mean disease-free survival (DFS) rate was 24.1 ± 2.5 months. The cumulative DFS rates in the first, second, and third years were 75.6%, 52.5%, and 28.2%, respectively. The number of tumours and tumour distribution were determined as prognostic factors. No major complication was detected, but six patients (13.9%) developed minor complications after MWA.ConclusionsMicrowave ablation in patients with hepatocellular carcinoma is a safety treatment modality with very low rates of complications. It offers an effective treatment with a high rate of complete response and local disease control according to the short-term results. In the long term, it prolongs the survival time of the treated patients. The number of tumours and tumour distribution were determined as prognostic factors affecting survival rates.

Prevention and treatment of the toxic tumour syndrome following primary proton beam therapy of choroidal melanomas

IntroductionThe aim of this study was to evaluate the efficacy and safety of endoresection for choroidal melanoma to prevent and treat the toxic tumour syndrome (TTS).Material and methodsThirteen patients who underwent primary proton beam therapy (PBRT) for choroidal melanoma followed by endoresection were evaluated. Main outcome measures were functional and anatomical results, surgical complications, rate of local recurrence, presence or absence of metastatic spread.ResultsThe median time of the follow-up period was 61.6 months. Six patients with clinical signs of TTS and seven with large tumours to prevent TTS underwent endoresection. Tumour thickness was 5.8 to 9.3 mm (mean: 7.6), the basal diameters were 10.6 to 15.0 mm (mean: 13.4). Preoperative best corrected visual acuity (BCVA) was 6/7.5 to counting fingers and the final BCVA was 6/15 to no light perception, and was better in those treated to prevent TTS (p = 0.01). The most universal early postoperative complication was bleeding from the scleral bed. The most common late postoperative complications were epiretinal membrane formation (30.8%), cystoid macular oedema (23.1%) and silicone oil-induced glaucoma (15.4%). Two (15.4%) patients developed phthisis bulbi, neither developed local recurrence. One patient developed liver metastases.ConclusionsEndoresection for choroidal melanoma is a safe and effective procedure with a high rate of local tumour control. The procedure appears to be useful in the prophylaxis and treatment of TTS after PBRT of choroidal melanoma.

Appropriate endpoints for stereotactic body radiotherapy for bone metastasis: Classification into five treatment groups.

Treatment of bone metastasis using stereotactic body radiotherapy (SBRT) is being widely used in clinical practice. The reported clinical advantages of SBRT include high pain and local control rates, high response rates against bone metastasis from radio-resistant tumors, and safe re-irradiations. Although most reports in the literature use local control as the primary treatment endpoint, this endpoint is not appropriate because local control does not relate directly to patient benefit. Herein, we proposed five pathophysiology-based patient groups, as well as appropriate endpoints for each group.

Benefit of postoperative radiotherapy for early tumors with single ipsilateral lymph node metastasis.

Indication for postoperative radiotherapy in patients with locally circumscribed tumors (pT1-pT2) and a single ipsilateral lymph node metastasis (pN1) is debatable. The aim of this study was to evaluate the oncological long-term outcome of patients with pT1-pT2 pN1 squamous cell carcinoma (SCC) of the oral cavity, the oropharynx, and the hypopharynx without extracapsular spread (ECS) after a margin-negative surgical resection, who either received or did not receive postoperative (chemo)radiotherapy. Retrospective case series. The oncological outcome of patients with pT1-pT2 pN1 SCC without ECS was evaluated retrospectively. All patients underwent primary tumor resection that included transoral laser microsurgery and neck dissection at an academic tertiary referral center. Of 65 identified patients treated between 1986 and 2015 (18 oral cavity, 30 oropharynx, 17 hypopharynx), 21 (32%) received postoperative radiotherapy, and 44 (68%) were treated by surgery alone. The group of patients receiving postoperative treatment showed a significantly superior 5-year disease-specific (94.4% vs. 73.2%, P = .029) and recurrence-free survival (85.2% vs. 43.2%, P = .002), as well as a higher local control rate (90.2% vs. 64.9%, P = .042). The overall survival was 71.4% vs. 62.6% (P = .53). The mean follow-up was 80.7 months. Patients with locally circumscribed carcinomas and a single ipsilateral ECS-negative lymph node metastasis seem to benefit from postoperative radiotherapy. 4 Laryngoscope, 130:E530-E538, 2020.

Assessment of precision irradiation in early non-small cell lung cancer and interstitial lung disease (ASPIRE-ILD): study protocol for a phase II trial

BackgroundStereotactic ablative radiotherapy (SABR) has become an established treatment option for medically-inoperable early-stage (Stage I-IIA) non-small cell lung cancer (ES-NSCLC). SABR is able to obtain high rates of local control with low rates of symptomatic toxicity in this patient population. However, in a subset of patients with fibrotic interstitial lung disease (ILD), elevated rates of SABR-related toxicity and mortality have been described. The Assessment of Precision Irradiation in Early Non-Small Cell Lung Cancer and Interstitial Lung Disease (ASPIRE-ILD) study will conduct a thorough prospective evaluation of the clinical outcomes, toxicity, changes in diagnostic test parameters and patient-related outcomes following SABR for ES-NSCLC for patients with fibrotic ILD.MethodsASPIRE-ILD is a single-arm Phase II prospective study. The accrual target is 39 adult patients with T1–2N0M0 non-small cell lung cancer with co-existing ILD who are not candidates for surgical excision. Pathological confirmation of diagnosis is strongly recommended but not strictly required. Enrolled patients will be stratified by ILD-related mortality risk. The starting SABR dose will be 50 Gy in 5 fractions every other day (biologically effective dose: 100 Gy10 or 217 Gy3), but the radiation dose can be de-escalated up to two times to 50 Gy in 10 fractions daily (75 Gy10 or 133 Gy3) and 45 Gy in 15 fractions daily (58 Gy10 or 90 Gy3). Dose de-escalation will occur if 2 or more of the first 7 patients in a cohort experiences grade 5 toxicity within 6 months of treatment. Similarly, dose de-escalation can also occur if 2 or more of the first 7 patients with a specific subtype of ILD experiences grade 5 toxicity within 6 months of treatment. The primary endpoint is overall survival. Secondary endpoints include toxicity (CTC-AE 4.0), progression-free survival, local control, patient-reported outcomes (cough severity and quality of life), rates of ILD exacerbation and changes in pulmonary function tests/high-resolution computed tomography findings post-SABR.DiscussionASPIRE-ILD will be the first prospective study specifically designed to comprehensively evaluate the effectiveness and safety of SABR for ES-NSCLC in patients with co-existing ILD.Trial registrationClinicaltrials.gov identifier: NCT03485378. Date of registration: April 2, 2018.

Treatment approaches for radiation maculopathy and retinopathy

AbstractToday it is possible to irradiate tumours, which would have been enucleated in the past and in addition remain high local tumor control rates. This is a consequence of our increasing understanding of irradiation‐induced side effects. The development of radiation‐induced maculopathy and retinopathy remain one of the most significant risk factors for visual impairment and secondary enucleation after irradiation. Therefore, it is essential to identify patients at risk and to offer them an appropriate treatment at the right time. The use of ultra‐wide field angiography offers us the possibility to detect early stages of peripheral ischemia to sufficiently treat patients with pan‐retinal photocoagulation. The consequent use of intravitreal VEGF‐inhibitors and corticosteroids gives us the opportunity to impede or at least delay the development of visual impairment due to radiation maculopathy. If possible, one should already try and spare or at least reduce the dose to vulnerable structures without compromising the local tumor control, when choosing the source of irradiation or during the planning procedure.

High-dose intensity-modulated chemoradiotherapy in vulvar squamous cell carcinoma: Outcome and toxicity

IntroductionTo evaluate clinical outcomes, pattern of failure, and toxicity after high-dose intensity-modulated radiation therapy (IMRT) for advanced vulvar cancer. MethodsIn this IRB approved retrospective study, the charts of women with histologically confirmed, non-metastatic vulvar cancer consecutively treated at our institution from 2012 to 2018 were reviewed to identify patients that received high-dose IMRT with curative intent. The treatment compliance, toxicities, and patterns of failure were investigated. Actuarial local, regional and distant recurrence and survival were estimated using Kaplan-Meier method and compared using log rank test. ResultsTwenty-six patients were identified, 23 were unresectable, and 3 refused surgery. Fifteen patients (58%) had inguinal node metastases; 10(38%) had pelvic node metastases. Elective surgical staging of groins was performed in 9-patients. Median tumor dose was 65.4Gy. Concurrent platinum-based chemotherapy was administered in 22(84.6%) patients. Complete response (CR) was achieved in 21/26 (80.7%) patients. Five patients had persistent disease following treatment and one sustained recurrence 5-months following radiotherapy. All persistent or recurrent disease occurred inside the irradiated volume. Median follow-up was 19 months (3–52 months). Actuarial 1-year local, regional and distant controls were 72.4%, 85.4%, and 86%, respectively. One and 2-year overall survivals were 91% and 62%, respectively. Complete response at 3-months was a strong predictor for overall survival (1-yr OS 73% vs 27%, HR 7.1 (95% CI 1.2–44); p = 0.01). Lymph node metastases adversely affected overall survival (2-yr OS 49% vs. 83%, p = 0.09). Grade 3–4 late urinary and soft-tissue toxicity was seen in 5 patients. Tumor doses >66 Gy (p = 0.03) and prior pelvic radiotherapy (p = 0.002) predicted grade 3–4 toxicity. ConclusionHigh-dose IMRT for vulvar cancer achieves high rates of local control with acceptable dose dependent long-term toxicity.

Stereotactic Body Radiotherapy for Spinal Metastases at the Extreme Ends of the Spine: Imaging-Based Outcomes for Cervical and Sacral Metastases.

The unique anatomy and biomechanical features of the cervical spine and sacrum may impact treatment outcomes following spine stereotactic body radiotherapy (SBRT). Current data for spine metastases are not specific for these locations. To report imaging-based SBRT outcomes to cervical and sacral metastases. We retrospectively reviewed our prospective spine SBRT database for cervical and sacral metastases. Patients were followed at 2- to 3-mo intervals with a clinical visit and full spine magnetic resonance imaging (MRI) and we report overall survival (OS), vertebral compression fracture (VCF), and MR imaging-based local control (LC) rates. Fifty-two patients and 93 treated spinal segments were identified. Fifty-six segments were within the cervical spine and 37 within the sacrum, the median follow-up was 14.4 and 19.5 mo, and the median total dose/number of fractions was 24 Gy/2, respectively. Cumulative LC at 1 and 2 yr were 94.5% and 92.7% for the cervical cohort, and 86.5% and 78.7% in the sacral cohort, respectively. Lack of posterior spinal element involvement in the cervical spine (P<.0001) and absence of epidural disease (hazard ratio 0.275, 95% confidence interval 0.076-0.989, P=.048) in the sacral cohort predicted LC. Median OS was 16.3 and 28.5 mo in the cervical spine and sacrum cohorts, respectively. Two cases of sacral VCF, 1 brachial plexopathy, and 1 lumbar-sacral plexopathy were observed. Although high rates of LC were observed, strategies specific to the sacrum may require further optimization.

Intraoperative radiotherapy (IORT) for surgically resected brain metastases: outcome analysis of an international cooperative study.

The ideal delivery of radiation to the surgical cavity of brain metastases (BMs) remains the subject of debate. Risks of local failure (LF) and radiation necrosis (RN) have prompted a reappraisal of the timing and/or modality of this critical component of BM management. IORT delivered at the time of resection for BMs requiring surgery offers the potential for improved local control (LC) afforded by the elimination of delay in time to initiation of radiation following surgery, decreased uncertainty in target delineation, and the possibility of dose escalation beyond that seen in stereotactic radiosurgery (SRS). This study provides a retrospective analysis with identification of potential predictors of outcomes. Retrospective data was collected on patients treated with IORT immediately following surgical resection of BMs at three institutions according to the approval of individual IRBs. All patients were treated with 50kV portable linear accelerator using spherical applicators ranging from 1.5 to 4.0 cm. Statistical analyses were performed using IBM SPSS with endpoints of LC, DBC, incidence of RN, and overall survival (OS) and p < 0.05 considered significant. 54 patients were treated with IORT with a median age of 64 years. The most common primary diagnosis was non-small cell lung cancer (40%) with the most common location in the frontal lobe (38%). Median follow-up was 7.2 months and 1-year LC, DBC, and OS were 88%, 58%, and 73%, respectively. LMD was identified in 2 patients (3%) and RN present in 4 patients (7%). The only predictor of LC was extent of resection with 1-year LC of 94% for GTR versus 62% for STR (p = 0.049). IORT is a safe and effective means of delivering adjuvant radiation to the BM resection cavities with high rates of LC and low incidence of RN. Further studies are warranted directly comparing LC outcomes to SRS.

Stereotactic Radiosurgery for Large Benign Intracranial Tumors

Historically, it is stated that large intracranial tumors, herein defined as a maximum dimension of ≥3 cm or tumor volume ≥14.2 cm3, are not candidates for stereotactic radiosurgery (SRS). We report outcomes of patients with large benign intracranial tumors treated with SRS. With institutional review board approval, we retrospectively identified 74 patients with large benign intracranial tumors (59 meningiomas, 9 vestibular schwannomas, and 6 glomus jugulare tumors) treated with robotic SRS (2007-2018). Patients received definitive SRS in 47.3% of the cases, adjuvant to surgical resection in 44.6%, and salvage after past radiation treatment in 8.1%. A median tumor volume of 16.0 cm3 (range, 10.1-65.5 cm3) received a median dose of 24.0 Gy (range, 14.0-30.0 Gy) in a median of 3 fractions (range, 1-5), for a median single fraction equivalent dose (with alpha/beta of 3) of 14.8 Gy (range, 11.3-18.0 Gy). The Kaplan-Meier estimate of tumor local control (LC) was calculated from date of SRS. With a median clinical follow-up of 32.8 months (range, 0.6-125.9 months) and median radiologic follow-up of 28.5 months (range, 0.6-121.4 months), LC was 96.5% (95% confidence interval, 92.4%-100%) at 3 years and 91.7% (95% confidence interval, 87.6%-95.7%) at 5 years. Adverse radiation effect (ARE) was seen in 10 patients (13.5%) at a median of 13.5 months (range, 7.8-34.5 months). ARE occurred in 9% of those with prior treatment compared with 5% who were radiation-naïve (P= 0.23). With 236.4 person-years of follow-up, no secondary malignancies were seen. Despite the historical adage, we find that SRS provides high rates of LC for these large tumors, with rates of ARE similar to historical reports of SRS for smaller benign tumors.

Intraoperative radiotherapy (IORT) for surgically resected brain metastases: Local control and dosimetric analysis.

114 Background: The optimal use of adjuvant radiation following surgical resection of large brain metastases (BM) remains undetermined. Time to initiation following surgery and target delineation both impact local control (LC). Intraoperative radiotherapy (IORT) allows for elimination of lag time between surgery and radiation, direct cavity targeting, and safe dose escalation beyond traditional stereotactic radiosurgery (SRS). The current study provides an analysis of local disease control and dosimetric parameters related to intracranial IORT. Methods: Retrospective data was collected on patients treated with IORT immediately following surgical resection of BMs at three institutions according to the approval of individual IRBs. All patients were treated with the Zeiss Intrabeam device (Carl Zeiss Meditech, Germany) using spherical applicators ranging from 1.5 to 4.0cm with 50kV output. Statistical analyses were performed using SPSS (IBM) with endpoints of LC and incidence of RN, with p &lt; 0.05 considered significant. Dosimetric comparisons between IORT and SRS were made based on V10, V12, and dose homogeneity based on percent of GTV receiving greater than 20Gy or 30Gy. Results: 54 patients were treated with IORT with a median age of 64 years. The most common primary diagnosis was non-small cell lung cancer (40%) with the most common location in the frontal lobe (38%). Median follow-up was 7.2 months and 1-year LC rate was 88% with radiation necrosis (RN) present in 4 patients (7%). The dosimetric comparison of a single IORT case revealed non-target V10 and V12 volumes as 24.75cm3 and 14.76cm3, respectively, for the SRS treatment plan of 16Gy to the margin. The V10 and V12 for the IORT treatment plan were 20.83cm3 and 9.93cm3 with a surface dose of 30Gy. The volumes exceeding 20Gy and 30Gy in the SRS plan were 14.73cm3 and 0.328cm3, respectively, while the corresponding volumes in the IORT plan were 9.8cm3 and 0cm3. Conclusions: IORT is a safe and effective means of delivering adjuvant radiation to the BM resection cavities with a high rate of LC, low incidence of RN, increased homogeneity of target dose and ability to escalate dose beyond traditional SRS plans.