Local Tumor Control Rate Research Articles

Thermal-ablation of vertebral metastases prevents adverse events in patients with differentiated thyroid carcinoma

PurposeTo evaluate a strategy that used thermal-ablation of vertebral metastases (VM) to prevent vertebral related events (VRE) in patients with differentiated thyroid cancer (DTC). MethodsThis single center study retrospectively reviewed records and post-operative imaging of all DTC patients treated with thermal-ablation for asymptomatic VMs. Rate of local tumor control at first post-operative imaging, 12 and 24 months after thermal-ablation and rate of VREs at 12 and 24 months among the treated VMs were reported. New VMs that occurred during the follow-up and were not considered for additional thermal-ablation were moniroted and VREs were reported. ResultsThermal-ablation was used to achieve local control of 41 VMs in 28 patients. Median post-treatment follow-up was 22 months [range: 12–80] and the mean delay for first post-operative imaging was 2 months [range: 0.6–7.5]. Local control at first post-operative imaging, 12 and 24 months was achieved in 87.8%, 82.9% and 75.6%, respectively. Among the treated VMs the rates of VRE was 7.3% at 2 years, significantly lower if local control was achieved at first post-operative imaging than if it was not (0% vs 30%, p = 0.011, OR = 0.184 [95%CI = 0.094–0.360]). After thermal-ablation procedures, 19 news VMs occurred in 11 patients (39.2%) with a median interval of 8 months [range 1–26] and remained untreated. Among these untreated VMs, the rate of VREs at 2 years was significantly higher compared to the treated VMs: (36.8% vs. 7.3%, p = 0.008, OR = 0.135, [95%CI = 0.030-0.607]). Conclusionlocal tumor control of VMs using thermal-ablation decreases the risk of VREs in DTC patients.

Single-Isocenter/Multi-Lesion Synchronous Lung Stereotactic Body Radiation Therapy (SBRT): Plan Quality, Treatment Efficiency and Clinical Outcomes

Patients with multiple primary or metastatic lung lesions may not well tolerate relatively longer SBRT treatments due to distress or shortness of breath, with traditional treatment planning and delivery with individual isocenter per lesion. Treating lesions synchronously with a single-isocenter volumetric modulated arc therapy (VMAT) plan with flattening filter free (FFF) beam will decrease treatment time and improve patient comfort. We report dosimetry, treatment efficiency and early clinical outcomes of oligometastases (< 5 lesions) lung cancer patients who underwent synchronous single-isocenter/multiple-lesions VMAT lung SBRT. Fourteen patients with multiple peripherally located non-small-cell-lung cancer (NSCLC) lesions (two n = 12, three n = 1, five n = 1, total 32 lesions) were treated synchronously with highly conformal single-isocenter non-coplanar VMAT-SBRT plan (bilateral lesions n = 6, right lesions n = 5, left lesions n = 3). Single-isocenter was placed between or in the middle of all lesions. Doses were 54 Gy/50 Gy in 3/5 fractions prescribed to 70-80% isodose line. Plans were generated with Acuros-based algorithm and 6MV-FFF beam following RTOG criteria. Plan quality and delivery efficiency were reported. Outcomes evaluated include local control rates, radiation pneumonitis and rib toxicity. Kaplan-Meier (KM) estimates of time-to-local failure were investigated. Median follow-up time was 5 ± 5 months (range 1 to 15 months). Mean isocenter to tumor distance was 5.6 ± 1.9 cm. Mean combined planning target volume (PTV) was 38.7 ± 22.7 cc. All plans were accepted by treating physicians and met RTOG criteria for target coverage and organs at risk (OAR) dose. Average values of conformity index, gradient index, maximum dose at 2 cm away from the PTV and normal lung V20 were 1.05 ± 0.1, 5.1 ± 0.8, 50.1 ± 5.2% and 6.4 ± 3.1%, respectively. All OAR doses were well below RTOG criteria. Additionally, normal lung V10, V5 and mean lung dose were 18.2%, 31.0 % and 5.4 Gy, on average, respectively. Average beam on time was 3.4 ± 1.4 min. One patient died before follow up and one was lost to follow up. Of twelve patients, eleven achieved complete response to treatment with one lesion of one patient progressing. KM estimated 1-year actuarial tumor local control rate was 100%; however, 50% of the patients developed distant metastases. During the follow-up period, no patient had adverse pulmonary effects, developed grade+2 pneumonitis or had chest wall pain/rib fracture. However, four patients developed radiographic changes that were asymptomatic. Synchronous SBRT treatment to oligometastases lung lesions was fast, effective and safe, with promising early clinical outcomes in terms of local control rates and no adverse side effects to lung or ribs. Although six patients had distant failure, the local control of treated lesions could preserve the patient’s quality of life or delay chemotherapy treatment. Longer follow up of these patients is warranted.

Stereotactic Radiosurgery With and Without Checkpoint Inhibition for Patients with Metastatic Non-Small Cell Lung Cancer to the Brain: A Matched Cohort Study

Abstract INTRODUCTION Immune checkpoint inhibitors (ICIs) improve survival in patients with advanced non-small cell lung cancer (NSCLC). Clinical trials examining the efficacy of ICI in patients with NSCLC excluded patients with untreated brain metastases (BM). As stereotactic radiosurgery (SRS) is commonly employed for NSCLC-BMs, we sought to define the safety, radiologic/clinical outcomes for patients with NSCLC-BM treated with concurrent ICI/SRS. METHODS A retrospective, matched cohort study was performed on patients who underwent SRS to one or more NSCLC-derived BM. Two matched cohorts were identified: one who received ICI within 3-mo of SRS (concurrent-ICI) and one who did not (ICI-naive). Locoregional tumor control, peritumoral edema, and central nervous system adverse events were compared. RESULTS A total of 17 patients (45-BMs) and 34 patients (92-BMs) comprised the concurrent-ICI and ICI-naive cohorts, respectively. Per RANO criteria, there was no difference in overall-survival (HR 0.99, 95% CI: 0.39-2.52) or CNS progression-free-survival (HR 2.18, 95% CI 0.72-6.62) between both groups. Similarly, the 12-mo local tumor control rate was 84.9% and 76.3% for tumors in the concurrent-ICI and ICI-naive cohorts, respectively (P = .94). Nevertheless, patients receiving concurrent-ICI had increased rates of complete response for BMs treated with SRS (50% vs 15.6%; P = .012) per RANO criteria. There was a shorter median time to BM regression in the concurrent-ICI cohort (2.5-mo vs 3.1-mo, P &lt; .001). There was no increased rate of radiation necrosis or intratumoral hemorrhage in patients receiving concurrent-ICI (concurrent-ICI: 5.9%; ICI-naive: 2.9%, P = .99). There was no difference in the rate of peritumoral edema progression across both groups (concurrent-ICI: 11.1%, ICI-naive: 21.7%; P = .162). CONCLUSION The use of ICI/SRS to treat NSCLC-BM was well tolerated while providing more rapid BM regression. Concurrent-ICI did not increase rates of peritumoral edema, radiation necrosis, or intratumoral hemorrhage. Further studies are needed to evaluate whether concurrent ICI/SRS improves PFS/OS for patients with metastatic NSCLC.

Single-fraction versus hypofractionated stereotactic radiosurgery for medium-sized brain metastases of 2.5 to 3cm.

Given recently suggested utility of hypofractionated stereotactic radiosurgery (SRS) in treating large brain metastases (BMs) > 3cm, we sought to prospectively control tumor size variable to investigate the efficacy and safety of hypofractionated SRS for medium-sized BMs (2.5 to 3cm) compared with single-fraction SRS. Between 2011 and 2015, a total of 100 patients with newly diagnosed BMs (n = 105) of 2.5 to 3cm had been treated with either single-fraction (n = 67; median dose 20Gy) or hypofractionated SRS (n = 38; median cumulative dose 35Gy in 5 daily fractions). No patients received any prior or upfront whole brain radiotherapy. In each patient, treatment outcome was measured by local tumor control (LTC), overall and progression-free survival (OS and PFS), and the occurrence of radiation necrosis (RN). With a median follow-up of 14months, significant differences were observed between the single-fraction versus hypofractionated SRS groups in the incidence of RN (29.9% vs. 5.3%, P < 0.001) and LTC (1-year LTC rates 66.6% vs. 92.4%, P = 0.028). There were no differences in PFS (median 6months vs. 6months, P = 0.381) and OS (median 13months vs. 18months, P = 0.239). Treatment-related adverse events ( ≥ grade 2 toxicity by CTCAE ver. 4.0) occurred more frequently in single-fraction group, although the difference did not reach statistical significance (56.3% vs. 36.1%, P = 0.084). Our results suggest a better safety and efficacy profile of hypofractionated SRS for medium-sized BMs compared with single-fraction SRS. Further prospective studies are needed to confirm these results.

Safety and Efficacy of Percutaneous Image-guided Cryoablation of Completely Endophytic Renal Masses

ObjectiveTo evaluate the safety, efficacy, and oncologic control of percutaneous image-guided cryoablation in the treatment of completely endophytic renal masses. Percutaneous image-guided cryoablation is a minimally invasive and effective treatment for small renal masses. Image-guided cryoablation is an attractive treatment for completely endophytic tumors given the challenge in visualization of such lesions during surgical extirpation. Materials and MethodsA retrospective study evaluating percutaneous cryoablation of completely endophytic renal masses with normal overlying renal cortex was performed. From January 2003 to December 2015, 200 endophytic renal masses (RENAL score 3 – endophytic/exophytic) were identified from an internal renal ablation database. After imaging review, 49 tumors with completely intact overlying renal cortex in 47 patients were included in the study. Outcomes, including complications and oncologic efficacy were evaluated according to standard nomenclature. ResultsPatients comprised 37 men and 10 women (mean age 64.0 years) who underwent 48 cryoablation procedures to treat 49 renal masses. Mean tumor size was 2.5 ± 0.5 cm. Major complications occurred following 5 of the 48 (10%) procedures. Forty of 46 (87%) tumors with imaging follow-up were recurrence-free at a mean of 56 months. Five of six local recurrences were successfully retreated with cryoablatoin. ConclusionPercutaneous thermal ablation of completely endophytic renal masses is a relatively safe procedure associated with acceptable complication and local tumor control rates. Given the complexities associated with partial nephrectomy, percutaneous cryoablation may be considered an alternative treatment for these select patients. Long-term follow-up studies are necessary to determine the durable efficacy of this treatment.

Patient Outcomes after Reirradiation of Small Skull Base Tumors using Stereotactic Body Radiotherapy, Intensity Modulated Radiotherapy, or Proton Therapy.

Purpose The aim of this study was to evaluate outcomes of patients who received reirradiation for small skull base tumors utilizing either intensity modulated radiotherapy (IMRT), stereotactic body radiotherapy (SBRT), and proton radiotherapy (PRT). Methods Patients who received IMRT, SBRT or PRT reirradiation for recurrent or new small skull base tumors (< 60 cc) between April 2000 and July 2016 were identified. Those with < 3 months follow-up were excluded. Clinical outcomes and treatment toxicity were assessed. The Kaplan-Meier method was used to estimate the local control (LC), regional control (RC), distant control (DC), progression free survival (PFS), and overall survival (OS). Results Of the 75 patients eligible, 30 (40%) received SBRT, 30 (40%) received IMRT, and 15 (20%) received PRT. The median retreatment volume was 28 cc. The median reirradiation dose was 66 Gy in 33 fractions for IMRT/PRT, and 45 Gy in 5 fractions for SBRT. The median time to reirradiation was 41 months. With a median follow-up of 24 months, the LC, RC, DC, PFS, and OS rates were 84%, 79%, 82%, 60%, and 87% at 1 year, and 75%, 72%, 80%, 49%, and 74% at 2 years. There was no difference in OS between radiation modalities. The 1- and 2-year late Grade 3 toxicity rates were 3% and 11% respectively.. Conclusions Reirradiation of small skull base tumors utilizing IMRT, PRT, or SBRT provided good local tumor control and low rates of Grade 3 late toxicity. A prospective clinical trial is needed to guide selection of radiation treatment modalities.

Progress of cancer radiotherapy combined with immunotherapy

Radiotherapy can improve the local control rate of the tumors by destructing the tumor cells within the radiation field, can reduce the distant spread by activating the body's anti-tumor immune response through various mechanisms, and also can exert systemic anti-tumor effect synergistically assisted by immunotherapy. As a new combination therapy, a large number of studies have found that local radiotherapy combined with different immunotherapy can benefit the survival of cancer patients. The optimal efficacy is closely related to the appropriate radiotherapy dose, segmentation model and combined timing. This paper discusses the effects of radiotherapy on the immune system, the related basic and clinical researches of radiotherapy and immunotherapy, and the better way to make the combination effectively. Key words: Neoplasms; Immunotherapy; Radiotherapy

Stereotactic radiosurgery with and without checkpoint inhibition for patients with metastatic non-small cell lung cancer to the brain: a matched cohort study.

Immune checkpoint inhibitors (ICIs) improve survival in patients with advanced non-small cell lung cancer (NSCLC). Clinical trials examining the efficacy of ICIs in patients with NSCLC excluded patients with untreated brain metastases (BMs). As stereotactic radiosurgery (SRS) is commonly employed for NSCLC-BMs, the authors sought to define the safety and radiological and clinical outcomes for patients with NSCLC-BMs treated with concurrent ICI and SRS. A retrospective matched cohort study was performed on patients who had undergone SRS for one or more NSCLC-derived BMs. Two matched cohorts were identified: one that received ICI before or after SRS within a 3-month period (concurrent ICI) and one that did not (ICI naive). Locoregional tumor control, peritumoral edema, and central nervous system (CNS) adverse events were compared between the two cohorts. Seventeen patients (45 BMs) and 34 patients (92 BMs) composed the concurrent-ICI and ICI-naive cohorts, respectively. There was no statistically significant difference in overall survival (HR 0.99, 95% CI 0.39-2.52, p = 0.99) or CNS progression-free survival (HR 2.18, 95% CI 0.72-6.62, p = 0.11) between the two groups. Similarly, the 12-month local tumor control rate was 84.9% for tumors in the concurrent-ICI cohort versus 76.3% for tumors in the ICI-naive cohort (p = 0.94). Further analysis did reveal that patients receiving concurrent ICI had increased rates of CNS complete response for BMs treated with SRS (8/16 [50%] vs 5/32 [15.6%], p = 0.012) per the Response Assessment in Neuro-Oncology (RANO) criteria. There was also a shorter median time to BM regression in the concurrent-ICI cohort (2.5 vs 3.1 months, p < 0.0001). There was no increased rate of radiation necrosis or intratumoral hemorrhage in the patients receiving concurrent ICI (5.9% vs 2.9% in ICI-naive cohort, p = 0.99). There was no significant difference in the rate of peritumoral edema progression between the two groups (concurrent ICI: 11.1%, ICI naive: 21.7%, p = 0.162). The concurrent use of ICI and SRS to treat NSCLC-BM was well tolerated while providing more rapid BM regression. Concurrent ICI did not increase peritumoral edema or rates of radiation necrosis. Further studies are needed to evaluate whether combined ICI and SRS improves progression-free survival and overall survival for patients with metastatic NSCLC.

Indicator for local recurrence of hepatocellular carcinoma after proton beam therapy: analysis of attenuation difference between the irradiated tumor and liver parenchyma on contrast enhancement CT.

We aimed to identify dynamic CT features that can be used for prediction of local recurrence of hepatocellular carcinoma (HCC) after proton beam therapy (PBT). We retrospectively retrieved CT scans of patients with PBT-treated HCC, taken between January 2004 and December 2016. 17 recurrent lesions and 34 non-recurrent lesions were retrieved. The attenuation difference between irradiated tumor and irradiated parenchyma (ADHCC-IP) was compared in the two groups by using the Mann-Whitney U test. Cut-off value of ADHCC-IP was estimated by using the Youden index. The follow-up time after PBT initiation ranged from 374 to 2402 days (median, 1069 days) in recurrent lesions, and 418 to 2923 days (median, 1091.5 days) in non-recurrent lesions (p = 0.892). The time until appearance of local recurrence after PBT initiation ranged from 189 to 2270 days (median, 497 days). ADHCC-IP of recurrent lesions [mean, -21.8 Hounsfield units (HU); from -95 to -31 HU] was significantly greater than that of non-recurrent lesions (mean, -51.7 HU; from -117 to -12 HU) at 1-2 years in portal venous phase (p = 0.039). 5-year local tumor control rates were 0.93 and 0.56 in lesions with ADHCC-IP at 1-2 years in PVP < -55 and ≥ -55 HU, respectively. The attenuation difference between irradiated HCC and irradiated liver parenchyma in portal venous phase at 1-2 years after PBT can predict long-term local recurrence of HCC after treatment. We identified a cut-off value for contrast enhancement of HCC after PBT that could predict future local recurrence.

Radiation dose intensity and local tumour control of non-small cell lung cancer: A radiobiological modelling perspective

Several clinical situations call for the use of radiobiological principles as powerful clinical tools. The aim of this project is to examine the effect of radiotherapy dose intensity on local tumour control for non-small cell lung cancer (NSCLC) using the biological effective dose (BED) concept. A two-year tumour control probability (TCP) model was developed based on the linear-quadratic cell concept combined with Poisson statistics. The two-year local control outcome was analysed for the radiotherapy dose using the BEDs. The BED calculations and the TCP model were fitted to a series of NSCLC patients drawn from the literature. The investigation is based on the two-year local tumour control rate for stage I-II NSCLC for a dose fractionation size that varied from 1.5-20 Gy per fraction delivered via three radiotherapy treatments: 3D-conformal radiation therapy (3D-CRT), continuous hyperfractionated accelerated radiotherapy (CHART) and stereotactic ablative body radiotherapy (SABR). The BED values of 2,280 patients were computed and analysed as a function of local tumour control. To quantitatively assess the correlation between the BED and local tumour control, a residuals analysis and linear regression were performed. Higher radiotherapy doses were associated with improved local tumour control and survival rates for NSCLC, as suggested by the coefficient of the correlation R2 statistical test: 0.83 for the 3D-CRT and 0.91 for the SABR treatment.

Petroclival meningiomas: long-term outcomes of multimodal treatments and management strategies based on 30 years of experience at a single institution.

A thorough investigation of the long-term outcomes and chronological changes of multimodal treatments for petroclival meningiomas is required to establish optimal management strategies. The authors retrospectively reviewed the long-term clinical outcomes of patients with petroclival meningioma according to various treatments, including various surgical approaches, and they suggest treatment strategies based on 30 years of experience at a single institution. Ninety-two patients with petroclival meningiomas were treated surgically at the authors' institution from 1986 to 2015. Patient demographics, overall survival, local tumor control rates, and functional outcomes according to multimodal treatments, as well as chronological change in management strategies, were evaluated. The mean clinical and radiological follow-up periods were 121 months (range 1-368 months) and 105 months (range 1-348 months), respectively. A posterior transpetrosal approach was most frequently selected and was followed in 44 patients (48%); a simple retrosigmoid approach, undertaken in 30 patients, was the second most common. The initial extent of resection and following adjuvant treatment modality were classified into 3 subgroups: gross-total resection (GTR) only in 13 patients; non-GTR treatment followed by adjuvant radiosurgery or radiation therapy (non-GTR+RS/RT) in 56 patients; and non-GTR without adjuvant treatment (non-GTR only) in 23 patients. The overall progression-free survival rate was 85.8% at 5 years and 81.2% at 10 years. Progression or recurrence rates according to each subgroup were 7.7%, 12.5%, and 30.4%, respectively. The authors' preferred multimodal treatment strategy, that of planned incomplete resection and subsequent adjuvant radiosurgery, is a feasible option for the management of patients with large petroclival meningiomas, considering both local tumor control and postoperative quality of life.

Radioablation of Hepatic Metastases from Renal Cell Carcinoma With Image-guided Interstitial Brachytherapy.

High-dose-rate interstitial brachytherapy (iBT) has been shown to provide high tumor control rates in the treatment of primary or secondary malignancies at various sites. The objective of this study was to evaluate the efficacy and safety of image-guided iBT in patients with metastatic renal cell carcinoma (mRCC). A total of 14 patients with a cumulative number of 54 unresectable RCC liver metastases after treatment with computed tomography (CT)- or open magnetic resonance imaging (MRI)-guided iBT using an iridium-192 source (single fraction irradiation) were included in this retrospective study. Local tumor control rate was 92.6% during a median follow-up of 10.2 months (range=2.4-73.6 months). Median progression-free survival after iBT was 3.4 months (range=1.0-27.8 months). Median overall survival was 51.2 months (range=10.2-81.5 months). No severe adverse events (grade 3 or more) were recorded. Image-guided iBT is a safe and feasible treatment in patients with mRCC.

Curative-intent radiotherapy for pediatric osteosarcoma: The St. Jude experience.

Radiation therapy (RT) confers local tumor control and survival advantages in some patients with osteosarcoma, yet pediatric and adolescent and young adult (AYA) population studies are limited. Twenty-eight patients treated with curative-intent RT (median dose, 59.4Gy; range, 40-76Gy) at our institution from 1990 to 2017 were retrospectively identified. Cumulative incidence (CIN) of local failure (LF) was estimated by Gray's method and overall survival (OS) by the Kaplan-Meier method. Competing-risk regression and Cox proportional hazards models determined predictors of outcome. Toxicity was reported according to CTCAE v4.0. With a median follow-up of 99.1 months in living patients, nine patients (32.1%) developed LF. Estimated CINs of LF with competing risk of death at 5 years for the entire cohort, patients at initial diagnosis (n = 16), and recurrent/refractory patients (n = 12) were 32.7% (95% CI, 16.0-50.5%), 25.0% (95% CI, 7.3-48.0%), and 43.8% (95% CI, 13.6-71.0%), respectively (P = 0.31). Estimated 5-year OS was 42.6% (95% CI, 23.2-62.0%), 54.6% (95% CI, 29.5-79.6%), and 24.3% (95% CI, 0-52.2%), respectively (P = 0.15). No clinicopathologic features were significantly associated with LF, yet lack of chemotherapy or metastasis at the time of RT was independent significant prognostic factors of decreased OS. Eleven patients experienced RT-related morbidity, with two grade 3 toxicities and no grade 4/5 events. Curative-intent RT in pediatric and AYA patients was well tolerated and achieved a local tumor control rate of 75% in patients with primary disease. Local control rates were similar to those in primarily adult studies, with similar or lower doses.

SUN-423 Nonhemorrhagic Pituitary Apoplexy Following CABG Surgery

Introduction: Pituitary apoplexy (PA) is a rare syndrome resulting from acute infarction, hemorrhage, or edema of the pituitary gland. Due to a wide variety of nonspecific symptoms and number of precipitating triggers, diagnosis can be challenging. Thus, a high level of suspicion must be maintained. Cardiac surgery with the utilization of cardiopulmonary bypass is a unique cause of PA that has an interesting pathophysiologic mechanism as an inciting factor. Knowledge of this is important as PA is a life-threatening condition with significant morbidity and mortality, especially in the perioperative period. Case: A 68-year-old male with a history of coronary artery disease status post recent coronary artery bypass graft presented on post-operative day 2 with acute blurry vision and visual field defects and remarkably no headache. MRI Brain revealed a heterogeneous intra- and suprasellar mass measuring 2.4 x 2.7 x 2.5 cm and expansion of the sella turcica with impingement of the optic chiasm, concerning for non-hemorrhagic PA in a previously undiagnosed pituitary macroadenoma. Laboratory workup was consistent with panhypopituitarism (except for central DI) for which he was immediately started on hormone replacement therapy with hydrocortisone and levothyroxine. Due to contraindication for surgery, fractionated intensity modulated radiation therapy was initiated delivering a total of 5400cGy of radiation in 30 fractions over 6 weeks. Serial post-radiation MRIs demonstrated dramatic decrease in pituitary macroadenoma size to 1.6 x 0.5 x 1.4 cm with complete resolution of sellar expansion, optic chiasm compression and his visual symptoms. Discussion: PA is a life-threatening syndrome that typically occurs in the setting of a pre-existing pituitary adenoma. Clinical diagnosis is made based upon sudden onset of symptoms within the syndrome of panhypopituitarism. Uniquely, cardiac surgery has been postulated as a cause of PA due to acute tumor expansion from cardiopulmonary bypass dynamics, which allow for infarction as a result of hemodilution, hypotension, and/or microembolism. PA is a clinical diagnosis which requires radiological confirmation with MRI with a sensitivity of 89-94%. Cases without signs of pituitary hemorrhage have a less severe clinical presentation and a better outcome. PA must be managed urgently by hormonal replacement. Definitive treatment is with surgical decompression and transphenoidal resection or radiotherapy. Radiotherapy is an option for refractory disease or non-surgical candidates showing excellent rates of local tumor control for non-functioning adenomas in particular. Due to its associated morbidity and mortality, it is important for clinicians to recognize PA as a rare perioperative complication of CABG that requires a high level of clinical suspicion to allow for prompt radiographic workup and treatment to ensure quality patient care.

MON-440 Cyberknife Radiosurgery for Functional and Non-Functional Pituitary Adenomas: Long-Term Single-Center Experience

Background: In recent years, CyberKnife radiosurgery (CKRS) has become an accepted adjuvant treatment modality when surgery has failed to achieve biochemical control of functional pituitary adenomas or after subtotal removal of non-secretory and secretory adenomas. However, long-term experience and clinical follow-up is limited. We present a retrospective review of our institutional experience with CKRS in patients with functional and non-functional pituitary adenomas. Methods: Forty-eight patients (23M/25F, age range 24-83 years) with pituitary adenomas received CKRS. Median follow-up period was 50 months (range 1 to 123 months). Patients consisted of 31 with non-functioning adenomas, 10 with acromegaly, 5 with Cushing disease (CD) and 2 with prolactinomas. Changes in hormonal function and treatment complications were analyzed in each case. Results: The ranges of radiation doses administered and prescription isodose line were 2500-3500 cGy/5 fractions and 62-78%, respectively. Pituitary hormone secretion improved in all 17 functioning adenomas, with hormonal normalization observed in 11/17 (65%) patients over median of 14 months. In patients with nonfunctioning adenomas, 4/31 (13%) patients subsequently developed panhypopituitarism over a median duration of 16 months. Radiological data was available in 42 patients, and 11/42 (26%) patients had reduction in tumor size over median of 16.5 months, 4/42 (10%) patients had local tumor recurrence over median of 41.5 months, and 27/11 (64%) patients had stable and unchanged tumor size. Of those with local tumor recurrence, 1 patient that had CD was treated with a low dose of 2500 cGy of salvage radiation therapy, 1 patient had Crooke’s changes after a dose of 2500 cGy salvage surgery, and 2 patients had high MIB scores (> 10). Post-treatment complications included temporal radiation-induced changes (n=2), 6th nerve palsy (n=1), and secondary malignancy (n=1). No patients developed visual field deficits. Five- and 7-year local progression free survival rates were 90% and 83%, respectively. Four patients died due to the following reasons: suicide, unknown reason, previously diagnosed testicular malignancy and infield neuroendocrine malignancy. Conclusion: We describe the long-term efficacy, safety and complication profile of CKRS in the treatment of functional and non-functional pituitary adenomas in our cohort of patients. Our data demonstrated that CKRS is a safe and effective adjunct for salvage therapy in patients with pituitary adenomas that have failed first-line therapy. In functioning pituitary adenomas, hormone hypersecretion improved in all patients, with the majority of patients achieving biochemical remission. Post-radiosurgery pituitary hormone deficiencies resulting in panhypopituitarism was observed in only a minority of patients. Overall, local tumor control and survival rates were relatively high.

Progress in image-guided radiotherapy for the treatment of non-small cell lung cancer.

Lung cancer is one of the most common malignant tumors. It has the highest incidence and mortality rate of all cancers worldwide. Late diagnosis of non-small cell lung cancer (NSCLC) is very common in clinical practice, and most patients miss the chance for radical surgery. Thus, radiotherapy plays an indispensable role in the treatment of NSCLC. Radiotherapy technology has evolved from the classic two-dimensional approach to three-dimensional conformal and intensity-modulated radiotherapy. However, how to ensure delivery of an accurate dose to the tumor while minimizing the irradiation of normal tissues remains a huge challenge for radiation oncologists, especially due to the positioning error between fractions and the autonomous movement of organs. In recent years, image-guided radiotherapy (IGRT) has greatly increased the accuracy of tumor irradiation while reducing the irradiation dose delivered to healthy tissues and organs. This paper presents a brief review of the definition of IGRT and the various technologies and applications of IGRT. IGRT can help ensure accurate dosing of the target area and reduce radiation damage to the surrounding normal tissue. IGRT may increase the local control rate of tumors and reduce the incidence of radio-therapeutic complications.

Fractionated CyberKnife Stereotactic Radiotherapy for Perioptic Pituitary Adenomas

Stereotactic radiosurgery (SRS) is the reference standard for radiotherapy for pituitary adenomas but has been limited to lesions with sufficient distance (i.e., >3 mm) from the optic apparatus. We used marginless, fractionated (i.e., 25-28 fractions) stereotactic radiotherapy and the CyberKnife to treat pituitary adenomas that were not eligible for SRS. We present the clinical outcomes, including local control, endocrine function, and toxicity from modern fractionated radiotherapy. A total of 53 patients were treated for pituitary adenomas within 3 mm of the optic apparatus. The primary endpoint was tumor control with the secondary endpoints of vision and pituitary function preservation and endocrine control in hormone-secreting tumors. The tumor control rate as measured on magnetic resonance imaging as either stable or decreased in size was 98.1% (52 of 53) at a mean follow-up of 32.5 months (range, 3-77). All patients experienced preservation or improvement of their preexisting vision status. No change in pituitary function was noted in 52 of the 53 patients (98.1%). One patient experienced worsening of pituitary function secondary to pituitary apoplexy that occurred 4 months after treatment. The endocrine control rate in hormone-secreting tumors was 75% (6 of 8). Marginless, fractionated CyberKnife radiotherapy demonstrated excellent local tumor control and endocrine control rates, comparable to those with SRS, with preservation of vision in patients with adenomas in close proximity to the optic pathway.

Combination therapy with TACE + ablation versus TACE + SBRT for hepatocellular carcinoma (HCC): Comparative analysis with propensity score-weighted cohorts.

443 Background: To assess the relative efficacy and toxicity associated with TACE+Ablation (Ablation) or TACE+SBRT (SBRT) in a large cohort of patients with unresectable HCC. Methods: Patients with HCC undergoing Ablation or SBRT from 2006-2016 with available follow up were included. Treatment groups were different at baseline regarding tumor stage (BCLC A, B and C: 96%, 4%, 0% (Ablation) vs. 73%, 14% and 13% (SBRT), P &lt; 0.001) and severity of liver disease (CTP A, B, and C: 55%, 45% and 0% (Ablation) vs. 50%, 41%, and 9% (SBRT), P = 0.007). Propensity scores were calculated with age, sex, BCLC stage, CTP class, etiology of liver disease, tumor number, and diameter to balance the cohorts. Average treatment effects on survival with multivariable propensity score-weighted competing risk Cox regression models were evaluated, with BCLC stage, number of treated tumors and liver transplant as additionally controlled variables. Primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS), local tumor control and hepatotoxicity. Treatment-related hepatotoxicity was defined as a two point change in CTP within six months after treatment. Results: 192 subjects were included (101 Ablation, 91 SBRT; median age=60 years, 75% men). Liver disease included HCV (78%), alcohol (35%) and NASH (8%). Liver transplant-adjusted 1- and 2-year OS rates were significantly greater for Ablation vs SBRT (88% vs. 75% and 77% vs. 50%, P&lt;0.001). 1-and 2-year PFS rates were significantly greater for Ablation vs. SBRT (84% vs. 65% and 75% vs. 51%, P &lt; 0.001). 1- and 2- year local tumor control rates were similar with both strategies (99% vs. 91% and 94% vs. 87%, P=0.298). Propensity score-weighted multivariable analysis showed significantly higher OS (sHR: 2.31, P = 0.006) and PFS rates (sHR:1.75, P = 0.008) with Ablation compared to SBRT. Ablation was also associated with lower post-treatment hepatotoxicity compared with SBRT (5% vs. 12%, P = 0.001). Conclusions: TACE+Ablation demonstrated higher OS/PFS and lower post-treatment hepatotoxicity compared with TACE+SBRT. Local disease control up to two years was equivocal, potentially suggesting equipoise for bridge to transplant.

Salvage Stereotactic Radiosurgery in Breast Cancer Patients with Multiple Brain Metastases

The overall survival rates for breast cancer are increasing due to controlled brain disease and improved systemic treatments. This study examined neurologic outcomes, tumor control, and survival data in breast cancer patients with multiple brain metastases and who required salvage stereotactic radiosurgery (SRS) for recurrent breast cancer brain metastases. The study included 231 patients with a primary diagnosis of breast cancer who underwent SRS for more than 1 brain metastases from May 1993 and July 2007. Survival analyses via univariate and multivariate Cox regression demonstrated interactions between survival and predictor values including Karnofsky Performance Scale, Recursive Partitioning Analysis Class, number of brain metastases, whole-brain radiotherapy (WBRT), immunotherapy, and chemotherapy. Of the 231 patients, the survival rate was 53% at 1 year and 26% at 5 years from initial SRS. Controlled systemic disease, adjuvant chemotherapy, and Recursive Partitioning Analysis class II were significant predictors of increased survival, while WBRT was a significant predictor of decreased survival. The median survival in patients who received WBRT after SRS was 11 months versus 23 months in those who did not. The local tumor control rate at initial follow-up was 95%. Of these, 40% of patients underwent additional brain SRS. Following salvage SRS, 8% of patients developed symptomatic adverse radiation events; however, the development of symptomatic adverse radiation events had no effect on patient survival. This report indicated that both initial and salvage SRS procedures in breast cancer patients with multiple brain metastases are effective for local control of intracranial disease while minimizing adverse radiation effects.

Clinical efficacy and safety evaluation of pemetrexed combined with radiotherapy in treatment of patients with lung adenocarcinoma brain metastasis.

Clinical efficacy and adverse reactions of pemetrexed combined with stereotactic gamma-ray radiotherapy in the treatment of patients with lung adenocarcinoma brain metastasis in The First People's Hospital of Yunnan Province were evaluated. A total of 67 patients with lung adenocarcinoma brain metastasis in experimental group were treated with simple pemetrexed chemotherapy, and then with radiotherapy, followed by pemetrexed chemotherapy. Their treatment results were compared with those of 53 patients treated with simple gamma knife in control group. The results were analyzed by comparing the clinical efficacy, side reactions, serum level changes, and survival between the two groups. Among 67 patients in the experimental group, there were 16 cases of complete response (CR), 39 cases of partial response (PR), 7 cases of stable disease (SD) and 5 cases of progressive disease (PD), with an effective rate of 82.09% (55/67) and a tumor local control rate of 92.54% (62/67). Among 53 patients in the control group, there were 13 cases of CR, 20 cases of PR, 9 cases of SD and 11 cases of PD, with an effective rate of 62.26% (33/53) and a tumor local control rate of 79.25% (42/53). There were statistically significant differences in the effective rate and local control rate between the two groups (P<0.05). The 6-, 12- and 24-month survival rates in experimental group were higher than those in control group (P<0.05). The main adverse reactions after pemetrexed combined with radiotherapy were lower than those after simple radiotherapy (P<0.05). The expression levels of the tumor markers carcinoembryonic antigen (CEA) and cytokeratin fragment antigen 21-1 (CYFRA21-1) in the two groups of patients after treatment were lower than those before treatment (P<0.05). After treatment, the expression levels of serum CEA and CYFRA21-1 in the experimental group were significantly lower than those in the control group (P<0.05). Pemetrexed combined with radiotherapy in the treatment of lung adenocarcinoma brain metastasis is more effective than simple radiotherapy, with lighter adverse reactions, worthy of clinical application and promotion.