Long-term Local Control Rates Research Articles

Fractionated Photofrin-Mediated Photodynamic Therapy Significantly Improves Long-Term Survival

This study investigates the effect of fractionated (two-part) PDT on the long-term local control rate (LCR) using the concentration of reactive oxygen species ([ROS]rx) as a dosimetry quantity. Groups with different fractionation schemes are examined, including a 2 h interval between light delivery sessions to cumulative fluences of 135, 180, and 225 J/cm2. While the total treatment time remains constant within each group, the division of treatment time between the first and second fractionations are explored to assess the impact on long-term survival at 90 days. In all preclinical studies, Photofrin is intravenously administered to mice at a concentration of 5 mg/kg, with an incubation period between 18 and 24 h before the first light delivery session. Fluence rate is fixed at 75 mW/cm2. Treatment ensues via a collimated laser beam, 1 cm in diameter, emitting light at 630 nm. Dosimetric quantities are assessed for all groups along with long-term (90 days) treatment outcomes. This study demonstrated a significant improvement in long-term survival after fractionated treatment schemes compared to single-fraction treatment, with the optimal 90-day survival increasing to 63%, 86%, and 100% vs. 20%, 25%, and 50%, respectively, for the three cumulative fluences. The threshold [ROS]rx for the optimal scheme of fractionated Photofrin-mediated PDT, set at 0.78 mM, is significantly lower than that for the single-fraction PDT, at 1.08 mM.

Long-Term Safety and Efficacy of SAbR for Metastatic RCC.

Metastasis-directed stereotactic ablative radiation (SAbR) in metastatic renal cell carcinoma (mRCC) has been shown to prolong time to systemic therapy start/change. However, there is a paucity of data on the durability of local control by SAbR and long-term side effects, limiting its investigation in prospective trials. Here we report the long-term local control rates of SAbR for mRCC, focusing on factors that lead to local failure where dose escalation may be beneficial. We retrospectively reviewed 354 metastatic RCC patients who received SAbR to 902 lesions between 2005 and September 2021. Acute and late adverse events and their Common Terminal Criteria for Adverse Events (CTCAE) v. 5.0 grades were collected. RECIST v. 1.1 was used to evaluate treatment response. LC was estimated using the cumulative incidence function, with death as a competing risk. Local control (LC) was calculated using the Kaplan-Meier method. Lesions were followed for a median of 16 months; 136 lesions had >36 months of follow-up. The most common radiation prescription was 36 Gy in 3 fractions, and the median biological effective dose was 72 Gy10. 3-year local control was 80% (95% CI 75, 83). 3-year LC differed according to lesion location, ranging from 65% (95% CI 52, 75) in the spine to 93% (95% CI 80, 98) in the lungs. Radiation-induced adverse events were experienced by 101 patients: 79 had an acute (≤90 days of SAbR) grade 1-2 toxicity; 20 had an acute grade 3-4 toxicity; 59 had a late grade 1-2 toxicity; 15 had a late grade 3-4 toxicity. The most common acute grade 1-2 toxicity was pain (n = 32), followed by nausea (n = 22) and fatigue (n = 16). There were 7 occurrences of acute grade 3-4 pain, 4 of nausea, and 2 fractures. The most common late grade 1-2 toxicity was fracture (n = 16), followed by pain (n = 15) and pneumonitis (n = 12). Hyperglycemia was the only late grade 3-4 toxicity that occurred more than once (n = 2). SAbR offers durable LC of mRCC lesions with an acceptable toxicity profile. LC was affected by treated lesion location, with bone (including long bones and ribs) and spine locations experiencing less durable LC, corresponding to locations that received lower-BED treatments.

Stereotactic Body Radiotherapy (SBRT) for Breast Cancer Spinal Metastases is Associated with Low Rates of Long-Term Local Failure (LF) and Vertebral Compression Fracture (VCF) Independent of Molecular Status

There is limited outcome data specific to breast cancer spinal metastases following spine SBRT. This study aims to report outcomes specific to breast cancer spinal metastases receiving spine SBRT and determine the implication of biomarker status. We have been maintaining a prospective database since the inception of the spine SBRT program. A retrospective review identified 168 breast cancer patients with 409 spinal segments treated with spine SBRT between January 2008 and January 2023. Molecular subtypes were grouped based on luminal A, luminal B, basal, and HER2 enriched. Patients were followed with q3-monthly full-spine MRI and a clinical assessment. The primary endpoint was MRI-based local failure (LF), and secondary endpoints were overall survival (OS) and vertebral compression fracture (VCF). The median follow-up was 33 months (range, 3.3-123 months). Amongst the 168 patients, the majority were ECOG 0 or 1 (95%), neurologically intact (94%), polymetastatic (74%), and either luminal A (71%) or luminal B (8%). A total of 17% of patients were HER2+ve versus 83% HER2-ve. Of 409 treated segments the majority (76%) had no prior radiation or surgery (de novo), were SINS stable (60%), had either no or low-grade epidural disease (86%) and treated with 24-28 Gy in 2 fractions (73%). The LF and OS rates at 1, 3, and 5 years were 5%, 11%, and 14%, respectively, and 91%, 65%, and 45%, respectively, independent of molecular subtype on univariate analyses. The cumulative risk of VCF at 2 and 5 years was 7% and 10%, respectively. We observe, in the largest breast cancer spine cohort to date, excellent long-term local control rates independent of molecular sub-group, and acceptable VCF rates.

Management of chordoma and chondrosarcoma with definitive dose-escalated single-fraction spine stereotactic radiosurgery.

The management of chordoma or chondrosarcoma involving the spine is often challenging due to adjacent critical structures and tumor radioresistance. Spine stereotactic radiosurgery (SSRS) has radiobiologic advantages compared with conventional radiotherapy, though there is limited evidence on SSRS in this population. We sought to characterize the long-term local control (LC) of patients treated with SSRS. We retrospectively reviewed patients with chordoma or chondrosarcoma treated with dose-escalated SSRS, defined as 24Gy in 1 fraction to the gross tumor volume. Overall survival (OS) was calculated by Kaplan-Meier functions. Competing risk analysis using the cause-specific hazard function estimated LC time. Fifteen patients, including 12 with chordoma and 3 with chondrosarcoma, with 22 lesions were included. SSRS intent was definitive, single-modality in 95% of cases (N = 21) and post-operative in 1 case (5%). After a median censored follow-up time of 5 years (IQR 4 to 8 years), median LC time was not reached (IQR 8 years to not reached), with LC rates of 100%, 100%, and 90% at 1 year, 2 years, and 5 years. The median OS was 8 years (IQR 3 years to not reached). Late grade 3 toxicity occurred after 23% of treatments (N = 5, fracture), all of which were managed successfully with stabilization. Definitive dose-escalated SSRS to 24Gy in 1 fraction appears to be a safe and effective treatment for achieving durable local control in chordoma or chondrosarcoma involving the spine, and may hold particular importance as a low-morbidity alternative to surgery in selected cases.

GPP04 Presentation Time: 8:30 AM: What is Appropriate Target Delineation for MRI-Based Brachytherapy for Medically Inoperable Endometrial Cancer?

<h3>Purpose</h3> While the incidence of medically inoperable endometrial cancer (MIEC) is anticipated to rise within the growing elderly population, practice patterns demonstrate persistent underutilization of brachytherapy (BT). Contemporary Image-guided BT (IGBT) offers superior target dose escalation while sparing adjacent organs at risk. However, the volumetric target of IGBT techniques is not well established. We propose a high-risk CTV (HRCTV) concept and report associated rates of local control and toxicity. <h3>Materials and Methods</h3> A retrospective review identified all patients with MIEC receiving definitive external beam radiotherapy (EBRT) followed by MRI-based IGBT at a single institution. BT dose was prescribed to a HRCTV defined as gross tumor volume plus endometrial cavity with a planning goal of a summed equivalent dose at 2Gy/fraction (EQD2) D90 of 85Gy or greater. An additional intermediate-risk volume (IRCTV) was developed by global 5mm expansion upon this HRCTV, removing any volume entering into organs at risk (OAR). The myometrium and uninvolved uterine body was not defined as target volume. OARs including rectum, bladder, sigmoid and bowel were limited to EQD2 constraints directly adapted from cervical cancer. Late gastrointestinal (GI), genitourinary (GU), and vaginal toxicity events were graded using CTCAE, version 5.0. Clinical endpoints including local progression-free survival (LPFS), progression-free survival (PFS), and overall survival (OS) were estimated via the Kaplan Meier method. <h3>Results</h3> 32 patients received MRI-based HDR-BT for MIEC between 12/2015 and 8/2020, with a median follow up of 19.8 months (IQR 8.9 - 27.6 months). Patients were a median 71.5 years at diagnosis (range, 43 - 91 years), with a median ECOG 1 performance status (IQR 1 - 2). FIGO stages included 1A (56%), IB (16%), II (3%), III (22%), and IV (3%). Common histologies included endometrioid (56%), serous adenocarcinoma (22%), and carcinosarcoma (13%). All patients completed EBRT (45 Gy/25 fractions, 69%; 50.4 Gy/28 fractions, 16%; other, 16%) followed by MRI-guided HDR-BT (27.5 Gy/5 fractions, 66%; 28 Gy/4 fractions, 28%; other, 6%). Composite dosimetry included the following median EQD2 values: D90 HRCTV 91.3 Gy (IQR 88.2 - 96.4 Gy), D98 HRCTV 78.2 Gy (73.7 - 82.6 Gy), D90 IRCTV 73.4 Gy (69.9 - 76.0 Gy), D2cc Bladder 72.9 Gy (66.7 - 76.4 Gy), D2cc Rectum 57.0 Gy (52.1 - 66.0 Gy), D2cc Sigmoid 65.0 Gy (63.3 - 70.3 Gy), D2cc Bowel 60.2 Gy (53.2 - 66.0 Gy), and D2cc Vagina 82.9 Gy (79.9 - 90.6 Gy). 16% of patients received hormonal therapy, and 3% of patients received chemotherapy. Figure 1 provides LPFS, PFS, and OS. There were 14 (44%) total deaths, 3 local recurrences (9%), 3 nodal recurrences (9%), and 5 distant recurrences (16%). 2-year LPFS was 88.8%, and 2-year OS was 65.8%, with no locoregional or distant progression observed beyond 24 months post-BT. For the 3 patients with local progression, median D90 HRCTV was 99.2 Gy (range 77.9 - 103.5 Gy), D98 HRCTV 80.2 Gy (68.6 - 89.4 Gy), and D90 IRCTV 73.3 Gy (66.0 - 83.5 Gy). For patients with stage I/II disease (n=24), LPFS was 100% at 12 months and 94% (95% CI 81.9 - 100%) at 24 months. 23 (72%) patients experienced no RT-related toxicity. Two grade 3+ toxicities (6%) were observed: one grade 3 vomiting event prompting hospitalization and one grade 5 GI bleed presumed secondary to RT-induced proctitis in the setting of longstanding clopidogrel use. <h3>Conclusions</h3> Patients with MIEC receiving definitive EBRT followed by MRI-based IGBT demonstrated high rates of long-term local control with a favorable toxicity profile, when dose was prescribed to the MRI-defined GTV and endometrial cavity. These data compare favorably to historical controls despite a significant proportion of patients with locally advanced disease and/or aggressive histology.

Long-Term Results of Two Novel Weekly High Dose Palliative Radiotherapy Schedules in Un-Resectable or Metastatic Breast Cancers: Should We Clinically Chase Statistical Significance?

<h3>Purpose/Objective(s)</h3> In a developing country like India, large fungating breast cancers are not uncommon. This causes much deterioration in the quality of life attributed to the pain, growth of maggots, bleeding and discharge from the tumor. Surgery is often not feasible, and chemotherapy hardly brings any response in such aggressive lesions. Our initial results were presented in the last two consecutive ASTRO conferences. Our first paper showed the feasibility and safety of extreme hypo-fractionated radiotherapy (8 Gy weekly x 5 fractions) while the second one compared the toxicity and response outcomes of 40 Gy (8 Gy weekly x 5 fractions) versus 24 Gy (8 Gy x 3). This paper presents the long-term local control and survival rates between the two groups. <h3>Materials/Methods</h3> A total of 54 patients were enrolled in the study. 24 patients received 5 fractions of weekly 8 Gy to the involved breast, while 30 patients received 3 fractions of the same dose. Early and late toxicities were assessed using RTOG toxicity criteria and Harvard 4-point cosmesis respectively. All patients were planned with tangential photon beams, ensuring that the lungs and the heart are outside our treatment field. <h3>Results</h3> Out of the fifty-four patients, 45 (83%) patients were upfront metastatic, while the remaining were unresectable post-neoadjuvant chemotherapy. Thirty-eight (70%) of the patients were hormone receptor-negative, 23 (42%) patients were Her 2 Neu positive which were almost equally distributed between both arms. Overall, 44 patients (81%) had extensive skin involvement including ulcerations, fungating mass, extensive peud' orange and satellite nodules. All these patients were treated with bolus over the skin. The median largest size was 8cm (3.3cm-16cm). 25 patients (46%) succumbed to their disease, within a year of treatment, as expected in such an aggressive cohort. As reported earlier, 52% of the patients had greater than grade 2 dermatitis in the 40 Gy arm versus none of the patients who had dermatitis grade 2 or above in the 24 Gy arm (p=0.051). Again, as reported earlier, the cosmesis was significantly worse in the 40 Gy arm with 25 % of patients reporting fair or poor cosmesis as compared to none in the 24 Gy arm (p=0.052). Nine (37%) progressed in the 40 Gy arm, versus 16 (53%) in the 24 Gy arm with a median progression-free survival of 11.3months versus 13.6 months, favoring the arm with 40 Gy (p=0.04). There was a trend to increased overall survival in the 40 Gy arm (25 months versus 18 months), although this was not statistically significant (p=0.5). <h3>Conclusion</h3> This unique study compares two novel high doses of palliative radiotherapy for fungating, unresectable and chemo-resistant malignancies of the breast. The 24 Gy regimen can be safely used, with minimal concerns of toxicity and cosmesis. Although the toxicities and deterioration of cosmesis were higher for the 40 Gy arm, the statistically significant local disease control may warrant the use of this higher dose which may be individualized based on the size and nature of the lesion.

CT-based image-guided brachytherapy in uterine cervical cancer: Effect of tumor dose and volume on local control

To determine the optimal primary tumor dose for cervical cancer treatment using computed tomography (CT)-based image-guided brachytherapy (IGBT). We retrospectively reviewed 171 patients with cervical cancer who underwent both external beam radiation therapy (EBRT) and IGBT between May 2015 and December 2019. Majority of EBRT plan included central shielding technique. CT-based IGBT was performed weekly a median of three times. Magnetic resonance imaging preceded the first and third session of IGBT for target delineation. The median age of the patients was 64 years (range: 30-91 years). The median follow-up time for living patients was 43 months (range: 6-76 months). The 3-year local control rates according to the International Federation of Gynecology and Obstetrics (FIGO, 2008) stages were 89%, 100%, 92%, 89%, 78%, and 100% for stages IB, IIA, IIB, IIIA, IIIB, and IVA, respectively. The median EBRT dose to the central pelvis and parametrium/pelvic wall was 41.4 Gy and 50.4 Gy, respectively. Patients who received a cumulative 2 Gy equivalent dose (EQD2) (α/β = 10 Gy) of high-risk clinical target volume (HR CTV) D90% ≥ 75 Gy achieved a long-term local control rate of 93%, compared with 80% in those who received <75 Gy (p = 0.02). This is one of the largest CT-based IGBT series examining the treatment of cervical cancer based on the tumor dose-volume relationship. An HR CTV D90% ≥75 Gy was significantly associated with favorable local control in this study.

Local control and failure patterns after intensity modulated radiotherapy with reduced target volume delineation after induction chemotherapy for patients with T4 nasopharyngeal carcinoma

BackgroundThe delineation of target volume after induction chemotherapy(IC) for nasopharyngeal carcinoma(NPC) is currently controversial. In this study, we aimed to analyze the long-term local control(LC) and failure patterns of T4 NPC treated with reduced target volume radiotherapy after IC. MethodsFrom September 2007 to January 2013, 145 patients with T4 NPC were retrospectively reviewed. All patients received at least 1 cycle of IC followed by intensity modulated radiotherapy(IMRT). The gross tumor volume(GTV) was delineated according to the post-IC images for intracavity tumors and lymph nodes. The LC and overall survival (OS) rates were calculated using the Kaplan-Meier method. The location and extent of local failures were transferred to the pretreatment planning computed tomography (CT) for dosimetric analysis. ResultsWith a median follow-up time of 95 months (range, 16–142 months), 23 local failures were found. The estimated 10-year LC and OS rates were 81.1%and 54.8% respectively. Among the 20 local failures with available diagnostic images, 18(90%) occurred within the 95% isodose lines and were considered in-field failures and 2(10%) were marginal. There was no outside-field failure. ConclusionsIn-field failure was the major pattern of local failure for T4 NPC. IMRT with reduced target volume after IC seems to be feasible. Further researches exploring optimal volume and radiation dose for local advanced NPC in the era of IC are warranted.

Deviation From Consensus Contouring Guidelines Predicts Inferior Local Control After Spine Stereotactic Body Radiotherapy

<h3>Purpose/Objective(s)</h3> Stereotactic body radiotherapy (SBRT) is increasingly utilized for the treatment of spine metastasis. Although consensus guidelines for spine SBRT target delineation have been published, data regarding their impact on patient outcomes are limited. The goal of this study is to analyze predictive factors for long-term local control (LC) in a large, mature series. <h3>Materials/Methods</h3> Patients with de novo metastasis of the spine treated at an academic institution between 2009 and 2020 were retrospectively reviewed. Patients with prostate and hematologic malignancies were excluded. Variables examined included primary tumor type, prior surgery and radiation, location, disease extension into the epidural space and paraspinal soft tissue, adherence of target volume to consensus guidelines (retrospectively reviewed from treatment plans), and prescribed dose and fractionation. Target lesions and epidural disease (ED) were identified on MRIs obtained at the time of treatment planning within 4 weeks of SBRT delivery. ED was graded as minimal (Bilsky grade 0-1a), low grade (LG-ED, Bilsky grade 1b) and high grade (HG-ED, Bilsky grade 1c-3). Univariable and multivariable Cox proportional hazard models were constructed using the Fine and Gray competing risk method with death as a competing risk for local progression. <h3>Results</h3> A total of 360 discrete lesions in 283 patients were treated with SBRT. The majority of lesions received 24-27Gy in 2-3 fractions. At median follow up of 14.6 months (range 1.2-131.3), 68 lesions had local progression, with 1 and 2-year LC rate of 87.6% (95% CI 82.6-91.2%) and 73.8% (95% CI 66.3-80.0%), respectively. In total, 58 deviations (16.1%) from consensus contouring guidelines were identified. Targets treated before 2012 and sacral lesions were more likely to deviate from guidelines. On univariable analysis, deviation from guidelines was associated with inferior LC (hazard ratio [HR] 2.68, 95% confidence interval [CI] 1.65-4.34, <i>P</i> < 0.001). One-year LC was 89.6% (95% CI 84.1-93.3%) for targets that adhered to guidelines, vs 78.2% (95% CI 63.3-87.7%) for those with deviations. Other factors associated with inferior LC included ED (univariable HR 4.10 for LG-ED, 95% CI 1.77-9.53, <i>P</i> = 0.001; HR 4.24 for HG-ED, 95% CI 1.90-9.45, <i>P</i> < 0.001), gastrointestinal (GI) primary (HR 2.45, 95% CI 1.36-4.40, <i>P</i> = 0.003) and paraspinal extension (HR 2.46, 95% CI 1.43-4.22, <i>P</i> = 0.001). On multivariable analysis, deviation from guidelines (HR 2.56, 95% CI 1.55-4.22, <i>P</i> < 0.001), ED (HR 3.38 for LG-ED, 95% CI 1.43-7.96, <i>P</i> = 0.005; HR 3.45 for HG-ED, 95% CI 1.52-7.86, <i>P</i> = 0.003), GI primary (HR 2.19, 95% CI 1.19-4.02, <i>P</i> = 0.01) and paraspinal extension (HR 2.24, 95% 1.29-3.87, <i>P</i> = 0.004) demonstrated significant association with progression. <h3>Conclusion</h3> SBRT provides durable tumor control for spine metastasis. These data support the use of consensus contouring guidelines to maximize the likelihood of LC.

Neoadjuvant Concurrent Radiotherapy and Chemotherapy in Early Breast Cancer Patients: Long-Term Results of a Prospective Phase II Trial.

Simple SummaryThe originality of this prospective study is to use radiation therapy in association with chemotherapy before surgery and permit patients to preserve their breasts or to undergo immediate reconstruction. This neoadjuvant strategy can therefore allow one-stage breast reconstructive surgery, the so-called “reverse technique”.Background: Neoadjuvant concurrent radiochemotherapy makes it possible to increase the breast conservation rate. This study reports the long term outcome of this treatment. Methods: From 2001 to 2003, 59 women with T2–3 N0–2 M0 invasive breast cancer (BC) not amenable to upfront breast conserving treatment (BCS) were included in this prospective, non-randomized phase II study. Chemotherapy (CT) consisted of four cycles of continuous 5-FU infusion and Vinorelbine. Starting concurrently with the second CT cycle, normofractionated RT was delivered to the breast and LN. Breast surgery was then performed. Results: Median follow-up (FU) was 13 years [3–18]. BCS was performed in 41 (69%) patients and mastectomy in 18 patients, with pathological complete response rate of 27%. Overall and distant-disease free survivals rates at 13 years were 70.9% [95% CI 59.6–84.2] and 71.5% [95% CI 60.5–84.5] respectively. Loco regional and local controls rates were 83.4% [95% CI 73.2–95.0] and 92.1% [95% CI 83.7–100], respectively. Late toxicity (CTCAE-V3) was assessed in 51 patients (86%) with a median follow-up of 13 years. Fifteen presented grade 2 fibrosis (29.4%), 8 (15.7%) had telangiectasia, and 1 had radiodermatitis. Conclusions: This combined treatment provided high long-term local control rates with limited side-effects.

Risk factors of recurrence after postoperative electron beam radiation therapy for keloid: Comparison of long-term local control rate.

To investigate the new risk factors for keloid recurrence after postoperative electron beam radiotherapy (RT) and evaluate the effectiveness of tranilast in combination with electron beam RT by comparing the local control rate. Identifying patients at high risk of recurrence after postoperative RT for keloids remains a challenge. Besides, no study examined the effectiveness of tranilast in combination with RT after surgery for the prevention of keloids recurrence. This study included 75 lesions in 59 consecutive patients who had undergone postoperative RT at our institute. The follow-up period and prescription of tranilast were examined beside several potential risk factors, such as multiple lesions, size, and shape. The median follow-up was 72 months (range, 6-147 months). Twenty-one lesions in 17 patients recurred in a median of 12 months after treatment (range, 1-60 months). Local control rates of all 75 lesions were estimated as 93%, 78%, 70%, and 68% at 1, 2, 5, and 10 years. Multiple lesions constituted a significant risk of recurrence (P = 0.03). A larger long axis was significantly related to the recurrence (P < 0.01). Irregular shape was associated with a significantly worse local control rate (P = 0.02). There was no significant difference in the local control rate between patients receiving tranilast and those who did not (P = 0.52). Multiple lesions and irregular shape were risk factors of keloid recurrence after postoperative electron beam RT. The effectiveness of tranilast was not demonstrated in the study.

ESTRO IORT Task Force/ACROP recommendations for intraoperative radiation therapy with electrons (IOERT) in breast cancer

The aim of this review is to provide a comprehensive overview of the role of intraoperative radiation therapy with electrons (IOERT) in breast conserving therapy (BCT), both as partial breast irradiation (PBI) as well as anticipated boost (“IOERT-Boost”). For both applications, the criteria for patient selection, technical details/requirements, physical aspects and outcome data are presented. IOERT as PBIThe largest evidence comes from Italian studies, especially the ELIOT randomized trial. Investigators showed that the rate of in-breast relapses (IBR) in the IOERT group was significantly greater than with whole breast irradiation (WBI), even when within the pre-specified equivalence margin. Tumour sizes >2 cm, involved axillary nodes, Grade 3 and triple negative molecular subtypes emerged as statistically significant predictors of IBR. For patients at low risk for in-breast recurrence (ASTRO/ESTRO recommendations), full dose IOERT was isoeffective with standard WBI. Hence, several national guidelines now include this treatment strategy as one of the standard techniques for PBI in carefully selected patients. IOERT BoostThe largest evidence for boost IOERT preceding WBI comes from pooled analyses performed by the European Group of the International Society of Intraoperative Radiation Therapy (ISIORT Europe), where single boost doses (mostly around 10 Gy) preceded whole-breast irradiation (WBI) with 50 Gy (conventional fractionation). At median follow-up periods up to ten years, local recurrence rates around 1% were observed for low risk tumours. Higher local relapse rates were described for grade 3 tumours, triple negative breast cancer as well as for patients treated after primary systemic therapy for locally advanced tumours. Even in this settings, long-term (>5y) local tumour control rates beyond 95% were achieved. These encouraging results are interpreted as being attributable to utmost precision in dose delivery (by avoiding a “geographic and/or temporal miss”), and the possible radiobiological superiority of a single high dose fraction, compared to the conventionally fractionated boost.IOERT also showed favourable results in terms of cosmetic outcome, assumedly thanks to the small treated volumes combined with complete skin sparing.

Analysis of long-term outcome of image-guided volumetric modulated arc therapy (VMAT) for primary malignant tumor of the cervical spine

ABSTRACT Objective Retrospective analysis of the long-term clinical outcome and acute toxicity of the primary malignant tumor of cervical spine receiving CBCT image-guided VMAT. Methods Thirty patients with primary malignant tumor of the cervical spine included in our center, from December 2013 to January 2016, 28 patients were retrospectively studied. The prescription dosage 95% PTV volume dose was 44 Gy, 2.0 Gy/fraction, and a total of 22 times. The median PGTV synchronized volume dose was 60 Gy (45–62.1 Gy), median 2.5 Gy (2–2.7 Gy)/fraction. In volumetric modulated, two arc volumetric modulated arc therapy (VMAT) was used, with spinal cord dosage DMAX< 45 Gy. Early response rate and acute toxicities were analyzed. Result The follow-up duration was 6–76 months (median 53 months). At the end of follow-up of June 1, 2019, 78.6% (22/28) patients were still alive. 3 and 5-y local control rates were 67.3% and 56.5% while 3 and 5-y OS were both 78.6% in the whole group of patients, respectively. Fourteen patients with chordoma 5-y local control rates and OS were 57.1% and 85.7%, respectively. Nine patients with giant-cell tumor of bone had a 5-y local control rate and OS were 77.8% and 85.7%, respectively. The response rate for moderate pain or above was 80% (8/10). Eleven patients (39.3%) suffered from grade 1 acute skin toxicity. Twenty-four patients (85.7%) had grade 1/2 mucositis. No radiation-induced spinal cord injury was found. Conclusion The image-guided VMAT for primary malignant tumor of the cervical spine provided a satisfactory long-term local control rate.

Modern Radiation Therapy for Pituitary Adenoma: Review of Techniques and Outcomes.

Pituitary adenomas are benign tumors arising in the adenohypophysis and comprise 8%-20% of all reported primary brain tumors in the west. Transsphenoidal surgery with an aim to achieve complete tumor resection is the recommended first-line treatment for nonfunctioning as well as secretory pituitary adenoma. External beam radiation therapy (RT) has been demonstrated to be an effective treatment modality for pituitary adenoma, uncured by surgery and/or medical therapy, providing excellent long-term local control (>90%), but lower and variable rates (50%-80%) of biochemical remission in secretory tumors. The adoption of pituitary RT in the community has been limited due to concerns regarding potential late toxicity and long latency in normalization of hormonal hypersecretion. Over the years, technological advances in RT planning and delivery have resulted in progressive conformation of high doses to the target tissues while sparing adjacent neurovascular structures providing a favorable therapeutic index. The choice of RT technique should be based on size, site, and availability of infrastructure and expertise, with no significant differences between fractionated approaches and stereotactic radiosurgery (SRS). In contemporary clinical practice, the recommended dose of fractionated RT for pituitary adenoma is 45-50.4Gy in 25-28 fractions delivered over 5-6 weeks using modern high-precision techniques. The recommended dose of SRS given in a single fraction is 12-14Gy for nonfunctioning adenomas and 16-20Gy for secretory tumors. Late toxicity of pituitary RT includes hypopituitarism, neurocognitive impairment, neuropsychological dysfunction, optic neuropathy, cerebrovascular accidents, and second malignant neoplasms. Hence, RT in pituitary adenoma should be offered only to patients with residual, recurrent, progressive, or high-risk tumors with careful assessment of the benefit-risk ratio by an experienced multidisciplinary neurooncology team.

Neuroimaging and Stereotactic Body Radiation Therapy (SBRT) for Spine Metastasis.

Historically, management options for spinal metastases include surgery for stabilization and decompression and/or external beam radiation therapy (EBRT). EBRT is palliative in nature, as it lacks accurate targeting such that the prescribed radiation doses must be limited in order to maintain safety. Modern advancement in imaging and radiotherapy technology have facilitated the development of stereotactic body radiation therapy (SBRT), which provides increased targeted precision for radiation delivery to tumors resulting in lower overall toxicity, particularly to regional structures such as the spinal cord and esophagus, while delivering higher, more effective, and radically ablative radiation doses.Over the past decade, SBRT has been increasingly utilized as a method of treating spinal metastases either as the primary modality or following surgical intervention in both de novo and reirradiation setting. Numerous studies suggest that SBRT is associated with an 80% to 90% rate of 1-year local control across clinical scenarios. For example, studies of SBRT as the primary treatment modality suggest long-term local control rate of 80% to 95% for spinal metastases. Similarly, SBRT in the adjuvant setting following surgery is associated with local control rates ranging from 70% to 100%. Furthermore, because SBRT allows for lower dose to the spinal cord, it has also been used in patients who have had prior radiation therapy, with studies showing 66% to 93% local control in this scenario.

MTE07.01 From Radiation Oncology Perspective

MTE07.01 From Radiation Oncology Perspective

Five-year Long-term Outcomes of Stereotactic Body Radiation Therapy for Operable Versus Medically Inoperable Stage I Non–small-cell Lung Cancer: Analysis by Operability, Fractionation Regimen, Tumor Size, and Tumor Location

BackgroundStereotactic body radiation therapy (SBRT) is standard for medically inoperable stage I non–small-cell lung cancer (NSCLC) and is emerging as a surgical alternative in operable patients. However, limited long-term outcomes data exist, particularly according to operability. We hypothesized long-term local control (LC) and cancer-specific survival (CSS) would not differ by fractionation schedule, tumor size or location, or operability status, but overall survival (OS) would be higher for operable patients. Patients and MethodsAll consecutive patients with stage I (cT1-2aN0M0) NSCLC treated with SBRT from June 2009 to July 2013 were assessed. Thoracic surgeon evaluation determined operability. Local failure was defined as growth following initial tumor shrinkage or progression on consecutive scans. LC, CSS, and OS were calculated using Cox proportional hazards regression. ResultsA total of 186 patients (204 lesions) were analyzed. Most patients were inoperable (82%) with Eastern Cooperative Oncology Group performance status of 1 (59%) or 2 (26%). All lesions received biological effective doses ≥ 100 Gy most commonly (94%) in 3 to 5 fractions. The median follow-up was 4.0 years. LC at 2 and 5 years were 95.6% (95% confidence interval, 92%-99%) and 93.7% (95% confidence interval, 90%-98%), respectively. Compared with operable patients, inoperable patients did not have significant differences in 5-year LC (93.1% vs. 96.7%; P = .49), nodal failure (31.4% vs. 11.0%; P = .12), distant failure (12.2% vs. 10.4%; P = .98), or CSS (80.6% vs. 91.0%; P = .45) but trended towards worse OS (34.2% vs. 45.3%; P = .068). Tumor size, location, and fractionation did not significantly influence outcomes. ConclusionsSBRT has excellent, durable LC and CSS rates for early-stage NSCLC, although inoperable patients had somewhat lower OS than operable patients, likely owing to greater comorbidities.

Local control and fracture risk following stereotactic body radiation therapy for non-spine bone metastases

AimsTo report local control and toxicity rates for patients treated with stereotactic body radiotherapy (SBRT) for non-spine bone metastases. Methods and materialsEighty-one patients with 106 non-spine bone metastases were treated between 2011 and 2014 and retrospectively reviewed. Indications included: oligometastases (63%), oligoprogression (17.3%), retreatment (2.4%) or other (17.3%). Cumulative incidence function was used to assess local recurrence and fracture probability. Bivariate relationships were investigated based on selected patient, tumour and dose–volume factors. ResultsMean follow-up was 13 months (range, 0.25–45.6) and the median patient age was 66.4 years (range, 36–86). Most patients were male (60.5%) and the predominant histology prostate cancer (32%). Bone metastases were most commonly located in the pelvis (41.5%) and almost half sclerotic. The most common prescriptions were 30 Gy/5 (30.2%) and 35 Gy/5 (42.5%). The cumulative incidence of local recurrence at 6,18 and 24 months respectively was 4.7%, 8.3% and 13.3% with a mean time to local recurrence of 11.8 months (range, 3.9–23.4). A significant association was found between local recurrence and volume of the PTV (p = 0.02), with larger PTVs having a greater risk of local failure. Fracture was observed radiographically in the treatment volume in 9/106 (8.5%) of treated lesions and the mean time to fracture was 8.4 months (range, 0.7–32.5 months). With respect to predictors, a trend was observed for lytic lesions (p = 0.11) and female gender (p = 0.09). ConclusionsThe results of this study confirm that SBRT yields high rates of long-term local control for non-spine bone metastases with a low fracture risk.

Fractionated stereotactic radiotherapy for optic nerve gliomas

Optic nerve gliomas represent approximately 5% of all pediatric intracranial tumors. Due to the highly variable clinical course optimal treatment is still discussed controversial. Since they often have little or no growth potential there is a strong recommendation for wait-and-see strategies. In patients with progressive loss of vision or local tumor progression in MR imaging, fractionated radiotherapy provides the greatest possibility of vision preservation. Radiotherapy plays an important role in these challenging tumors achieving high long-term local control rates and improved or stable visual function in approximately 90% of the cases. Recommended dose prescriptions vary between 45 and 54 Gy in standard fractionation. However, in children less than 5 years of age the role of radiotherapy is unclear. Here, chemotherapy is often used to delay radiotherapy treatment to avoid neuropsychological morbidity after irradiation during neurodevelopment. Typical late complications of radiotherapy include endocrinopathy, vasculopathy, cognitive deficits and cataracts, especially in younger patients. Modern high-precision radiotherapy techniques like fractionated stereotactic radiotherapy (FSRT) are capable to achieve high local control rates with reduced treatment related late morbidity. Prospective randomised trials are needed to further define the role of modern radiotherapy techniques, especially in younger patients in a multimodal treatment approach.

Radiotherapy in patients with vestibular schwannoma and neurofibromatosis type 2: clinical results and review of the literature.

To evaluate the long-term outcome of patients with vestibular schwannoma (VS) and neurofibromatosis type 2 (NF2) treated with fractionated stereotactic radiotherapy (FSRT) or stereotactic radiosurgery (SRS). Sixteen VS in 14 patients with NF2 were treated with FSRT (n = 14) and SRS (n = 2). Patients with tumor progression and/or progression of clinical symptoms were selected for treatment. For patients treated with FSRT a median total dose of 57.6 Gy was prescribed with a median fractionation of 5 × 1.8 Gy per week. For patients who underwent SRS a median single dose of 17 Gy was prescribed to the 80% isodose. FSRT and SRS were well tolerated. Local control rate was 94% for a median follow-up time of 131 months; 2- and 5-year progression-free survival were 100%. The probability of maintaining the pretreatment hearing level was 44%. Useful hearing preservation was 33%. Cranial nerve toxicity was moderate. Trigeminal nerve function worsened in 2 patients (12%) and facial nerve function in 3 patients (19%). One patient developed a new tinnitus. FSRT and SRS are both safe and effective noninvasive and minimally invasive treatment options for patients with VS in the setting of NF2. The long-term local control rates are excellent. Functional hearing preservation is worse in patients with VS and NF2 than in patients with sporadic VS.