Image-guided Stereotactic Body Radiotherapy Research Articles

Image-Guided Stereotactic Body Radiotherapy on Detectable Prostate Bed Recurrence after Prostatectomy in RT-Naïve Patients.

Eighty-six patients who underwent SBRT for macroscopic bed recurrence after prostatectomy were retrospectively included. Patients were treated based on mpMRI or choline/PSMA PET. The median time to biochemical relapse (BCR) after RP was 46 months, with a median PSA at restaging of 1.04 ng/mL. Forty-six patients were staged with mpMRI and choline/PSMA PET, while ten and thirty were treated based on PET and MRI only, respectively. Only one late G ≥ 2 GI toxicity was observed. With a median BCR follow-up of 14 months, twenty-nine patients experienced a BCR with a median PSA at recurrence of 1.66 ng/mL and a median survival free from the event of 40.1 months. The median time to BCR was 17.9 months. Twenty-seven patients had clinical relapse (CR), with a median CR follow-up of 16.27 months and a median time to CR of 23.0 months. Biochemical recurrence-free survival at one and two years was 88% and 66%, respectively, while clinical recurrence-free survival at one and two years was 92% and 82%, respectively. Regarding local relapses, seven were in the field of treatment, while eight of them were outside the field of treatment. Data showed that SBRT targeting only the macroscopic bed recurrence instead of the whole prostate bed is safe and effective. Additional data and longer follow-ups will provide a clearer indication of the appropriate treatment and staging methodology for these patients.

REPeated mAgnetic resonance Image-guided stereotactic body Radiotherapy (MRIg-reSBRT) for oligometastatic patients: REPAIR, a mono-institutional retrospective study

BackgroundOligo-progression or further recurrence is an open issue in the multi-integrated management of oligometastatic disease (OMD). Re-irradiation with stereotactic body radiotherapy (re-SBRT) technique could represent a valuable treatment option to improve OMD clinical outcomes. MRI-guided allows real-time visualization of the target volumes and online adaptive radiotherapy (oART). The aim of this retrospective study is to evaluate the efficacy and toxicity profile of MRI-guided repeated SBRT (MRIg-reSBRT) in the OMD setting and propose a re-SBRT classification.MethodsWe retrospectively analyzed patients (pts) with recurrent liver metastases or abdominal metastatic lesions between 1 and 5 centimeters from liver candidate to MRIg-reSBRT showing geometric overlap between the different SBRT courses and assessing whether they were in field (type 1) or not (type 2).ResultsEighteen pts completed MRIg-reSBRT course for 25 metastatic hepatic/perihepatic lesions from July 2019 to January 2020. A total of 20 SBRT courses: 15 Type 1 re-SBRT (75%) and 5 Type 2 re-SBRT (25%) was delivered. Mean interval between the first SBRT and MRIg-reSBRT was 8,6 months. Mean prescribed dose for the first treatment was 43 Gy (range 24–50 Gy, mean BEDα/β10=93), while 41 Gy (range 16–50 Gy, mean BEDα/β10=92) for MRIg-reSBRT. Average liver dose was 3,9 Gy (range 1–10 Gy) and 3,7 Gy (range 1,6–8 Gy) for the first SBRT and MRIg-reSBRT, respectively. No acute or late toxicities were reported at a median follow-up of 10,7 months. The 1-year OS and PFS was 73,08% and 50%, respectively. Overall Clinical Benefit was 54%.ConclusionsMRIg-reSBRT could be considered an effective and safe option in the multi-integrated treatment of OMD.

Cardiac migration of an implanted hepatic fiducial marker used for stereotactic body radiation therapy - A case report.

Stereotactic body radiation therapy (SBRT) has been increasingly used to treat liver malignancies because large doses of radiation can be delivered precisely to the target with a rapid dose falloff. Real-time tracking of implanted fiducial markers (FMs), combined with respiratory gating, further improves the accuracy of treatment delivery and reduces the dose to critical structures. There have been reports of migration of the FMs after implantation for SBRT. Calypso beacons, which use the electromagnetic wave reflections for the image guidance, have recently been used for image-guided liver SBRT. In the literature, there are no reports on the migration of Calypso beacons to the heart after implantation in the liver. In this report, we detail the first case of such migration. Respiratory-gated SBRT guided by the Calypso system was planned for our patient, who developed liver metastases in segments 6 and 5/4B shortly after the completion of radical chemoradiotherapy for anal squamous cell carcinoma. One of the three Calypso beacons inserted in the liver under computed tomography (CT) guidance was found to have migrated to the right ventricle, as seen in CT simulation images. SBRT was delivered with respiratory gating using the remaining two beacons. A fluoroscopic imaging performed during treatment confirmed the migrated marker to the right ventricle. Patient denied any cardiac symptoms and SBRT were delivered uneventfully. Ten months later, the patient died of disease progression.

ESTRO clinical practice guideline: Stereotactic body radiotherapy for spine metastases

Background and purposeRecent progress in diagnostics and treatment of metastatic cancer patients have improved survival substantially. These developments also affect local therapies, with treatment aims shifting from short-term palliation to long-term symptom or disease control. There is consequently a need to better define the value of stereotactic body radiotherapy (SBRT) for the treatment of spinal metastases. MethodsThis ESTRO clinical practice guideline is based on a systematic literature review conducted according to PRISMA standards, which formed the basis for answering four key questions about the indication and practice of SBRT for spine metastases. ResultsThe analysis of the key questions based on current evidence yielded 22 recommendations and 5 statements with varying levels of endorsement, all achieving a consensus among experts of at least 75%. In the majority, the level of evidence supporting the recommendations and statements was moderate or expert opinion, only, indicating that spine SBRT is still an evolving field of clinical research. Recommendations were established concerning the selection of appropriate patients with painful spine metastases and oligometastatic disease. Recommendations about the practice of spinal SBRT covered technical planning aspects including dose and fractionation, patient positioning, immobilization and image-guided SBRT delivery. Finally, recommendations were developed regarding quality assurance protocols, including description of potential SBRT-related toxicity and risk mitigation strategies. ConclusionsThis ESTRO clinical practice guideline provides evidence-based recommendations and statements regarding the selection of patients with spinal metastases for SBRT and its safe implementation and practice. Enrollment of patients into well-designed prospective clinical trials addressing clinically relevant questions is considered important.

Randomized phase II trial of MRI-guided salvage radiotherapy for prostate cancer in 4 weeks versus 2 weeks (SHORTER)

BackgroundUltra-hypofractionated image-guided stereotactic body radiotherapy (SBRT) is increasingly used for definitive treatment of localized prostate cancer. Magnetic resonance imaging-guided radiotherapy (MRgRT) facilitates improved visualization, real-time tracking of targets and/or organs-at-risk (OAR), and capacity for adaptive planning which may translate to improved targeting and reduced toxicity to surrounding tissues. Given promising results from NRG-GU003 comparing conventional and moderate hypofractionation in the post-operative setting, there is growing interest in exploring ultra-hypofractionated post-operative regimens. It remains unclear whether this can be done safely and whether MRgRT may help mitigate potential toxicity. SHORTER (NCT04422132) is a phase II randomized trial prospectively evaluating whether salvage MRgRT delivered in 5 fractions versus 20 fractions is non-inferior with respect to gastrointestinal (GI) and genitourinary (GU) toxicities at 2-years post-treatment.MethodsA total of 136 patients will be randomized in a 1:1 ratio to salvage MRgRT in 5 fractions or 20 fractions using permuted block randomization. Patients will be stratified according to baseline Expanded Prostate Cancer Index Composite (EPIC) bowel and urinary domain scores as well as nodal treatment and androgen deprivation therapy (ADT). Patients undergoing 5 fractions will receive a total of 32.5 Gy over 2 weeks and patients undergoing 20 fractions will receive a total of 55 Gy over 4 weeks, with or without nodal coverage (25.5 Gy over 2 weeks and 42 Gy over 4 weeks) and ADT as per the investigator’s discretion. The co-primary endpoints are change scores in the bowel and the urinary domains of the EPIC. The change scores will reflect the 2-year score minus the pre-treatment (baseline) score. The secondary endpoints include safety endpoints, including change in GI and GU symptoms at 3, 6, 12 and 60 months from completion of treatment, and efficacy endpoints, including time to progression, prostate cancer specific survival and overall survival.DiscussionThe SHORTER trial is the first randomized phase II trial comparing toxicity of ultra-hypofractionated and hypofractionated MRgRT in the salvage setting. The primary hypothesis is that salvage MRgRT delivered in 5 fractions will not significantly increase GI and GU toxicities when compared to salvage MRgRT delivered in 20 fractions.Trial registrationClinicalTrials.gov Identifier: NCT04422132. Date of registration: June 9, 2020.

PD-0811 Image-guided Stereotactic Body Radiotherapy for intermediate and high-risk endometrial carcinoma

PD-0811 Image-guided Stereotactic Body Radiotherapy for intermediate and high-risk endometrial carcinoma

Stereotactic ablative body radiotherapy with a central high dose using CyberKnife for metastatic lung tumors

BackgroundThe CyberKnife system features a robotically-positioned linear accelerator to deliver real-time image-guided stereotactic ablative body radiotherapy (SABR). It achieves steep dose gradients using irradiation from hundreds of different directions and increases the central dose of the gross tumor volume (GTV) without increasing the marginal dose to the planning target volume. We evaluated the effectiveness and safety of SABR with a central high dose using CyberKnife for metastatic lung tumors.MethodsA total of 73 patients with 112 metastatic lung tumors treated with CyberKnife were retrospectively analyzed. Local control, progression-free survival, and overall survival were calculated using the Kaplan–Meier method. The median age was 69.2 years. The most common primary sites were the uterus (n = 34), colorectum (n = 24), head and neck (n = 17), and esophagus (n = 16). For peripheral lung tumors, the median radiation dose was 52 Gy in 4 fractions, whereas for centrally located lung tumors, it was 60 Gy in 8–10 fractions. The dose prescription was defined as 99% of the solid tumor components of the GTV. The median maximum dose within the GTV was 61.0 Gy. The GTV and planning target volume were enclosed conformally by the 80% and 70% isodose lines of the maximum dose, respectively. The median follow-up period was extended to 24.7 months; it was 33.0 months for survivors.ResultsThe 2-year local control, progression-free survival, and overall survival rates were 89.1%, 37.1%, and 71.3%, respectively. Toxicities of grade ≥ 2 were noted as grade 2 and 3 radiation pneumonitis in one patient each. The two patients with grade 2 or higher radiation pneumonitis had both received simultaneous irradiation at two or three metastatic lung tumor sites. No toxicity of grade ≥ 2 was observed in patients with metastasis in one lung only.ConclusionsSABR with a central high dose using CyberKnife for metastatic lung tumors is effective with acceptable toxicity.Trial registrationNumber: 20557, Name: Stereotactic ablative radiotherapy using CyberKnife for metastatic lung tumor, URL: http://www.radonc.med.osaka-u.ac.jp/pdf/SBRT.pdf, Date of registration: April 1, 2021 (retrospectively registered), Date of enrollment: May 1, 2014.

PSA Kinetics and Outcomes after Magnetic Resonance Image-Guided Stereotactic Body Radiotherapy for Prostate Cancer

<h3>Purpose/Objective(s)</h3> Using moderate or ultra-hypofractionation, which is also known as stereotactic body radiotherapy (SBRT) for treatment of localized prostate cancer patients has been increased. Assessment of the efficacy of treatment response after radiotherapy relies heavily on the monitoring of prostate specific antigen (PSA) levels and PSA kinetics. The aim of our study was to evaluate tumor control outcomes with PSA response and toxicity after magnetic resonance image-guided adaptive radiotherapy (MRgRT) for prostate cancer patients. <h3>Materials/Methods</h3> A total of 95 prostate cancer patients treated with MRgRT were included in the study. Treatment was performed with IMRT (step and shoot) technique and daily plan adaptation using MRgRT. Patients received 36.25 Gy in 5 fractions, per institutional standards. Outcome measurements included tumor control evaluation with PSA levels, acute and late toxicities. Nadir PSA was defined as the lowest serum PSA value from the time of SBRT completion to date of last follow-up. Biochemical failure (BCF) was defined using the Phoenix definition (nadir + 2 ng/mL). <h3>Results</h3> The median follow-up for our cohort was 23.7 months (range; 3-41.4 months). The median age was 74 years (range; 50-87 years). The median initial PSA (iPSA) was 7.6 ng/mL (range; 2.7-44 ng/mL) for all patients. According to the NCCN guidelines, 13 (13.7%), 53 (55.8%) and 29 (30.5%) patients were in low-, intermediate- and high-risk group, respectively. Twenty-nine patients (30.5%) received androgen deprivation therapy (ADT). The median nadir PSA (nPSA) for all patients was 0.72 ng/mL (range, 0.01-4.96 ng/mL). For the entire cohort, 52.6% patients had an nPSA <1 ng/mL, with 35.8% of patients reaching an nPSA 0.5 ng/mL and 20% reaching an nPSA 0.2 ng/mL. For the patients who didn't receive ADT, median nPSA was 1.26 ng/mL (range; 0.16-4.96 ng/mL); 45.0% patients had an nPSA <1 ng/mL, with 21.3% of patients reaching an nPSA 0.5 ng/mL and 3.3% reaching an nPSA 0.2 ng/mL. For the patients who received ADT, median nPSA was 0.06 ng/mL (range; 0.01-1.55 ng/mL); 95.8% patients had an nPSA <1 ng/mL, with 87.5% of patients reaching an nPSA 0.5 ng/mL and 70.8% reaching an nPSA 0.2 ng/mL. A patient who did not yet meet the Phoenix criteria for biochemical recurrence but a PSA rising was diagnosed with two bone metastases with imaging evaluation and one patient with a nPSA and positive PSMA-PET had radical prostatectomy. MRgRT was well tolerated by all patients. There was no Grade ≥3 GU or GI toxicity. <h3>Conclusion</h3> In conclusion, MRgRT represents a new method for delivering SBRT with markerless soft tissue visualization, online adaptive planning and real-time tracking. Our study suggests that ultra-hypofractionation with MRgRT has an acceptable toxicity profile with favorable efficacy and PSA response. Further studies with longer follow-up time and larger cohorts are warranted.

A Pilot Study of Durvalumab (MEDI4736) with Tremelimumab in Combination with Image-Guided Stereotactic Body Radiotherapy in the Treatment of Metastatic Anaplastic Thyroid Cancer.

Background: Metastatic anaplastic thyroid cancer (ATC) has a poor prognosis. This pilot study aims to evaluate tremelimumab plus durvalumab with stereotactic body radiotherapy (SBRT) to improve overall survival (OS). Methods: Eligible patients received up to 4 doses tremelimumab (75 mg) given q4 weeks and up to 1 year of durvalumab (1500 mg) given q4 weeks. SBRT at 9 Gy × 3 fractions was given within the first 2 weeks of the start of treatment. Paired biopsies (pretreatment and between 3 and 10 weeks after the first dose of the drug treatment) were done in the medically qualified patients. Major inclusion criteria are metastatic ATC, Eastern Cooperative Oncology Group (ECOG) performance status 0-2, no prior immunotherapy, and last anticancer treatment >7 days before starting the study. The primary endpoint was 1 year OS with the combination of durvalumab, tremelimumab, and SBRT in metastatic ATC patients with a target of 1 year OS in ≥2 out of 12 patients. Results: A total of 13 patients signed consent but only 12 patients ultimately participated in this trial. One patient who consented to the protocol became ineligible for this study due to continued decline in performance status. Patient characteristics were as follows: male (n = 6) with a median age of 71 years (range: 49-82), and ECOG = 1. Nine patients had prior neck radiation and nine patients had prior chemotherapy. Next-generation sequencing and PD-L1 staining were done in the nine patients where tissue was available. High microsatellite instability (MSI) corresponding to mismatch repair defect was noted in two patients. There were zero confirmed responses and only one patient had stable disease and was treated with ≥4 cycles of study drugs. The median time that the patients were under treatment was 11 weeks (1-28 weeks). MSI status did not affect treatment response. High MSI patients were on treatment for 8-14 weeks before disease progression. The median OS was 14.5 weeks with only 1 patient alive beyond 1 year. The presence of a BRAF or p53 mutation did not appear to affect treatment outcome. Conclusions: Tremelimumab and durvalumab with SBRT did not improve OS for ATC. Future research is needed to examine other novel immunotherapy combinations with or without radiotherapy in the treatment of ATC. Clinical Trial Registration: NCT03122496.

High-dose hypofractionated stereotactic body radiotherapy for spinal chordoma.

Spinal chordoma is locally aggressive and has a high rate of recurrence, even after en bloc resection. Conventionally fractionated adjuvant radiation leads to suboptimal tumor control, and data regarding hypofractionated regimens are limited. The authors hypothesized that neoadjuvant stereotactic body radiotherapy (SBRT) may overcome its intrinsic radioresistance, improve surgical margins, and allow preservation of critical structures during surgery. The purpose of this study is to review the feasibility and early outcomes of high-dose hypofractionated SBRT, with a focus on neoadjuvant SBRT. Electronic medical records of patients with spinal chordoma treated using image-guided SBRT between 2009 and 2019 at a single institution were retrospectively reviewed. Twenty-eight patients with 30 discrete lesions (24 in the mobile spine) were included. The median follow-up duration was 20.8 months (range 2.3-126.3 months). The median SBRT dose was 40 Gy (range 15-50 Gy) in 5 fractions (range 1-5 fractions). Seventeen patients (74% of those with newly diagnosed lesions) received neoadjuvant SBRT, of whom 15 (88%) underwent planned en bloc resection, all with negative margins. Two patients (12%) developed surgical wound-related complications after neoadjuvant SBRT and surgery, and 4 (two grade 3 and two grade 2) experienced postoperative complications unrelated to the surgical site. Of the remaining patients with newly diagnosed lesions, 5 received adjuvant SBRT for positive or close surgical margins, and 1 received SBRT alone. Seven recurrent lesions were treated with SBRT alone, including 2 after failure of prior conventional radiation. The 2-year overall survival rate was 92% (95% confidence interval [CI] 71%-98%). Patients with newly diagnosed chordoma had longer median survival (not reached) than those with recurrent lesions (27.7 months, p = 0.006). The 2-year local control rate was 96% (95% CI 74%-99%). Among patients with radiotherapy-naïve lesions, no local recurrence was observed with a biologically effective dose ≥ 140 Gy, maximum dose of the planning target volume (PTV) ≥ 47 Gy, mean dose of the PTV ≥ 39 Gy, or minimum dose to 80% of the PTV ≥ 36 Gy (5-fraction equivalent doses). All acute toxicities from SBRT were grade 1-2, and no myelopathy was observed. Neoadjuvant high-dose, hypofractionated SBRT for spinal chordoma is safe and does not increase surgical morbidities. Early outcomes at 2 years are promising, although long-term follow-up is pending.

Bi/Se-Based Nanotherapeutics Sensitize CT Image-Guided Stereotactic Body Radiotherapy through Reprogramming the Microenvironment of Hepatocellular Carcinoma.

The particular characteristics of hypoxia, immune suppression in the tumor microenvironment, and the lack of accurate imaging guidance lead to the limited effects of stereotactic body radiotherapy (SBRT) in reducing the recurrence rate and mortality of hepatocellular carcinoma (HCC). This research developed a novel theranostic agent based on Bi/Se nanoparticles (NPs), synthesized by a simple reduction reaction method for in vivo CT image-guided SBRT sensitization in mice. After loading Lenvatinib (Len), the obtained Bi/Se-Len NPs had excellent performance in reversing hypoxia and the immune suppression status of HCC. In vivo CT imaging results uncovered that the radiotherapy (RT) area could be accurately labeled after the injection of Bi/Se-Len NPs. Under Len's unique and robust properties, in vivo treatment was then carried out upon injection of Bi/Se-Len NPs, achieving excellent RT sensitization effects in a mouse HCC model. Comprehensive tests and histological stains revealed that Bi/Se-Len NPs could reshape and normalize tumor blood vessels, reduce the hypoxic situation of the tumor, and upregulate tumor-infiltrating CD4+ and CD8+ T lymphocytes around the tumors. Our work highlights an excellent proposal of Bi/Se-Len NPs as theranostic nanoparticles for image-guided HCC radiotherapy.

A decision tool for radiographer-led abdominal image-guided stereotactic ablative body radiotherapy - Experience from a single institution.

A decision tool for radiographer-led image-guided radiotherapy (IGRT) using cone-beam CT (CBCT) for abdominal stereotactic radiotherapy was developed and successfully implemented in a single department. The confidence of 7 therapeutic radiographers when undertaking online CBCT review increased, and the pooled median online match time was reduced by 1m 8s. While this may be advantageous for abdominal SABR, further evaluation of this work in a larger cohort is required to validate these results.

Fiducial-based image-guided SBRT for pancreatic adenocarcinoma: Does inter-and intra-fraction treatment variation warrant adaptive therapy?

PurposeVariation in target positioning represents a challenge to set-up reproducibility and reliability of dose delivery with stereotactic body radiation therapy (SBRT) for pancreatic adenocarcinoma (PDAC). While on-board imaging for fiducial matching allows for daily shifts to optimize target positioning, the magnitude of the shift as a result of inter- and intra-fraction variation may directly impact target coverage and dose to organs-at-risk. Herein, we characterize the variation patterns for PDAC patients treated at a high-volume institution with SBRT.MethodsWe reviewed 30 consecutive patients who received SBRT using active breathing coordination (ABC). Patients were aligned to bone and then subsequently shifted to fiducials. Inter-fraction and intra-fraction scans were reviewed to quantify the mean and maximum shift along each axis, and the shift magnitude. A linear regression model was conducted to investigate the relationship between the inter- and intra-fraction shifts.ResultsThe mean inter-fraction shift in the LR, AP, and SI axes was 3.1 ± 1.8 mm, 2.9 ± 1.7 mm, and 3.5 ± 2.2 mm, respectively, and the mean vector shift was 6.4 ± 2.3 mm. The mean intra-fraction shift in the LR, AP, and SI directions were 2.0 ± 0.9 mm, 2.0 ± 1.3 mm, and 2.3 ± 1.4 mm, respectively, and the mean vector shift was 4.3 ± 1.8 mm. A linear regression model showed a significant relationship between the inter- and intra-fraction shift in the AP and SI axis and the shift magnitude.ConclusionsClinically significant inter- and intra-fraction variation occurs during treatment of PDAC with SBRT even with a comprehensive motion management strategy that utilizes ABC. Future studies to investigate how these variations could lead to variation in the dose to the target and OAR should be investigated. Strategies to mitigate the dosimetric impact, including real time imaging and adaptive therapy, in select cases should be considered.

Toxicity and Outcomes of Re-Irradiation for Intra-Thoracic Recurrence Using Stereotactic Body Radiation Therapy (SBRT)

Patients treated for a thoracic malignancy carry a significant risk of developing other lung lesions. Locoregional control of intrathoracic recurrences is challenging due to the impact of prior therapies on normal tissues. We examined the safety and efficacy of thoracic re-irradiation using high-precision image-guided stereotactic body radiation therapy (SBRT). Records of 24 patients with prior intra-thoracic radiation therapy (RT) who underwent SBRT for a subsequent primary, recurrent or metastatic lung tumor from April/2013 to December/2018 were retrospectively reviewed. Survival duration was calculated from the date of start of re-irradiation. Overall survival (OS) rates and local progression-free survival (LPFS) rates were estimated using the Kaplan-Meier method. Acute and late toxicities were grated per CTCAE ver4. Toxicity rates were compared using univariate Cox proportional hazard models adjusted for age, gender, Eastern Cooperative Oncology Group performance status (ECOG PS), primary site (legion and characteristics), biologically effective prescription dose (α/β = 10) (BED10), interval time between prior RT and re-irradiation, tumor size, planning target volume (PTV), the volume of normal lung receiving ≥20 Gy (V20), and the mean lung dose (MLD). The median patient age was 75 years (range 44-92 years). 16 patients received prior RT for a primary lung cancer, 7 for metastases from other histologies, and 1 for a pleural tumor. Median dose of prior RT was 60 Gy (range 45–70 Gy). Median BED10 of SBRT was 102.5 Gy (range 48-180 Gy). With a median follow-up of 20.5 months among survivors, median OS time were 29 months. 2-year OS rates and LPFS rates were 77.9% and 58.8%, respectively. Grade 2 and 3 pulmonary toxicity, including dyspnea, cough, pleural effusion, pneumonitis and pneumothorax were observed in 25% and 8.3% of patients, respectively. No grade 5 events and pulmonary hemorrhage occurred. Univariate analysis demonstrated that PTV of re-irradiation was found to be associated with Grade2 radiation pneumonitis (P = 0.02). V20 and MLD of lung at re-irradiation were not significantly associated. Salvage SBRT for intrathoracic recurrences after initial RT appears safe, with low treatment related toxicity and encouraging rates of tumor control.

Image-Guided Hypofractionated Proton Therapy in Early-Stage Non-Small Cell Lung Cancer: A Phase 2 Study.

PurposeDue to the excellent outcomes with image-guided stereotactic body radiotherapy for patients with early-stage non–small cell lung cancer (NSCLC) and the low treatment-related toxicities using proton therapy (PT), we investigated treatment outcomes and toxicities when delivering hypofractionated PT.Materials and MethodsBetween 2009 and 2018, 22 patients with T1 to T2 N0M0 NSCLC (45% T1, 55% T2) received image-guided hypofractionated PT. The median age at diagnosis was 72 years (range, 58-90). Patients underwent 4-dimensional computed tomography simulation following fiducial marker placement, and daily image guidance was performed. Nine patients (41%) were treated with 48 GyRBE in 4 fractions for peripheral lesions, and 13 patients (59%) were treated with 60 GyRBE in 10 fractions for central lesions. Patients were assessed for CTCAEv4 toxicities with computed tomography imaging for tumor assessment. The primary endpoint was grade 3 to 5 toxicity at 1 year.ResultsThe median follow-up for all patients was 3.5 years (range, 0.2-8.8 years). The overall survival rates at 3 and 5 years were 81% and 49%, respectively. Cause-specific survival rates at 3 and 5 years were 100% and 75%, respectively. The 3-year local, regional, and distant control rates were 86%, 85%, and 95%, respectively. Four patients experienced in-field recurrences between 18 and 45 months after treatment. One patient (5%) developed a late grade 3 bronchial stricture requiring hospitalization and stent.ConclusionImage-guided hypofractionated PT for early-stage NSCLC provides promising local control and long-term survival with a low likelihood of toxicity. Regional nodal and distant relapses remain a problem.

Image-guided hypofractionated double-scattering proton therapy in the management of centrally-located early-stage non-small cell lung cancer

Background The treatment of centrally-located early-stage non-small cell lung cancer (NSCLC) with image-guided stereotactic body radiotherapy (SBRT) is challenging due to the proximity of critical normal structures to the tumor target. The purpose of this study was to report the results of our experience in treating centrally-located early-stage NSCLC with hypofractionated proton therapy (PT). Material and methods Between 2009 and 2018, 23 patients with T1–T2N0M0 NSCLC (T1, 46%; T2, 54%) were treated with image-guided hypofractionated double-scattering PT. The median age at the time of treatment was 74 years (range, 58–88). Patients underwent 4-dimensional computed tomography (CT) simulation following fiducial marker placement, and daily image guidance was performed. All patients were treated with 60 GyRBE in 10 fractions. Patients were assessed for CTCAEv4 toxicities weekly during treatment, and at regular follow-up intervals with CT imaging for tumor assessment. Overall survival, cause-specific survival, local control, regional control, and metastases-free survival were evaluated using cumulative incidence with competing risks. Results Median follow-up for all patients was 3.2 years (range, 0.2–9.2 years). Overall survival rates at 3 and 5 years were 81% and 50% (95% CI, 27–79%), respectively. Cause-specific survival rates at 3 and 5 years were 81% and 71% (95% CI, 46–92%). The 3-year local, regional, and distant control rates were 90%, 81%, and 87%, respectively. Three patients (13%) experienced local recurrences as their first recurrence, at a median time of 28 months from completion of radiation (range, 18–61 months). Two patients (9%) experienced late grade 3 toxicities, including 1 patient who developed a bronchial stricture that required stent placement. Conclusion Image-guided hypofractionated PT for centrally-located early-stage NSCLC provides excellent local control with low rates of grade ≥3 toxicities. For tumors in sensitive locations, PT may provide safer treatment than photon-based treatments due to its dosimetric advantages.

Proceedings to the 6th Annual Conference of the Particle Therapy Cooperative Group North America (PTCOG-NA): 14-16 October 2019, Hosted by Miami Cancer Institute, part of Baptist Health South Florida, Miami, FL, USA.

Proceedings to the 6th Annual Conference of the Particle Therapy Cooperative Group North America (PTCOG-NA): 14-16 October 2019, Hosted by Miami Cancer Institute, part of Baptist Health South Florida, Miami, FL, USA.

Premature Termination of a Randomized Controlled Trial on Image-Guided Stereotactic Body Radiotherapy of Metastatic Spinal Cord Compression.

It is possible to plan and treat some patients with stereotactic body radiotherapy (SBRT) in a timely fashion in an acute setting. Advanced and, in some indications, already implemented technologies such as SBRT are difficult to test in a randomized trial. Stereotactic body radiotherapy (SBRT) in metastatic spinal cord compression (MSCC) could be an alternative to decompressive surgery followed by fractionated radiotherapy. In a randomized, single-institution, noninferiority trial, patients with MSCC were assigned to stereotactic body radiotherapy of 16 Gy in 1 fraction or decompression surgery followed by fractionated radiotherapy of 30 Gy in 10 fractions. Primary endpoint was ability to walk by EQ5D-5L questionnaire. Based on power calculations, 130 patients had to be included to be 89% sure that a 15% difference between the treatment arm and the experimental arm could be detected. Ten patients were accrued in 23 months, with six patients allocated to surgery and four patients to stereotactic body radiotherapy. The trial was closed prematurely because of poor accrual. One patient undergoing surgery and one patient undergoing stereotactic body radiotherapy were unable to walk at 6 weeks. Two patients were not evaluable at 6 weeks. A randomized, phase II, clinical trial comparing surgery followed by fractionated radiotherapy or image-guided SBRT of MSCC was initiated. SBRT was shown to be feasible, with three out of four patients retaining walking function. The trial was determined futile as a result of low accrual.

Bowel and bladder reproducibility in image-guided SBRT prostate: Results of a patterns of practice survey.

76 Background: Use of prostate stereotactic body radiotherapy (SBRT) as treatment for localized prostate cancer (PCa) is increasing. Given the high dose (&gt;5Gy) per fraction (Fx) being delivered, SBRT requires careful preparation and delivery to ensure accuracy and precision. Guidelines and data on best practice for bowel and bladder preparation are lacking. Therefore, we surveyed practicing radiation oncologists (RO) to document practice patterns for prostate SBRT. Methods: From June to October 2018 we completed a nationwide survey of 1395 American Society for Therapeutic Radiology and Oncology (ASTRO) members who self-identified as managing PCa. A SurveyMonkey link was sent via email, and analysis included practicing RO who treat PCa with SBRT. Results: 204 responses were received with 32% (64/204) using SBRT. 80% (51/64) provided the fractionation used: 33% (17/51) use 35Gy to 36.25Gy, and 17.6% (9/51) use &gt;40Gy in 5 Fx, and 1 used &gt;9Gy Fx. 94% use implantable devices for localization (83% fiducial markers, 17% radiofrequency transponders). 65% (42/64) use a hydrogel spacer. 75% (48/64) use daily cone beam CT (CBCT) for image guidance. The majority use a 5 mm PTV, with 3 mm posteriorly. For bladder and bowel preparation 97% (62/64) provided preferences. For bladder, 90.3% (56/62) required a comfortably full bladder for both simulation and treatment. For simulation, 92% (57/62) have a bowel protocol (BP) to optimize rectal reproducibility. 51.6% (31/62) have patients empty their bowels prior, and 51.6% (31/62) prescribe a BP. Diet alteration was recommended by 77% (48/62). 86% (53/62) used a BP during SBRT treatment. Of those using a BP, 67% (43/64) continued it throughout SBRT with 30% (19/64) continuing BP unless symptoms change management. Only 3% (2/64) stop BP after simulation. Conclusions: The variability of data in the literature on effective BP for treatment reproducibility for PCa is reflected in the varied patterns of practice seen in our survey. Consensus on bladder preparation is seen for a majority of practitioners. A variety of BP regimens are employed.

MTE07.01 From Radiation Oncology Perspective

MTE07.01 From Radiation Oncology Perspective