Favorable Local Control Research Articles

RADT-50. CLINICAL OUTCOME OF DAILY 5-FRACTIONATED GAMMA KNIFE RADIOSURGERY FOR LARGE BRAIN METASTASES

Abstract INTRODUCTION With the introduction of the Gamma Knife Icon, hypo-fractionated Gamma Knife radiosurgery (GKRS) for large brain metastases (LBMs) is beginning to be performed. This study aimed to assess the clinical outcome and risk of the daily 5-fractionated GKRS for LBMs. METHODS A total of 100 patients who underwent 5-fractionated GKRS for LBMs (> 14cm3) were enrolled. Forty-six were male patients, and the median age was 60 years. Most common primary cancer sites were lung (41 non-small cell cancers), breast (24), and kidney (14). The median tumor volume was 22cm3 (14 – 69cm3) and marginal dose was 35Gy (50% isodose line) in 5 fractions. Median follow-up duration was 18 months (3 – 72 months). RESULTS The last follow-up showed local tumor control in 74 cases. The cumulative 1, 2, and 3-year local tumor control rates were 73, 65, and 60%, respectively. Eighty-six tumors showed best MRI response in a year, and median tumor volume decrease rate was 80% (22 – 100%). Thirty patients experienced dramatically tumor volume decrease (> 95%). Median progression free and overall survival were 7 and 16 months, respectively. Radiation necrosis occurred in 24 patients, of which only 9 had neurological symptoms and treated with steroid and bevacizumab. CONCLUSIONS The daily 5-fractionated GKRS for very LBMs showed favorable local tumor control and acceptable radiation necrosis, but questionable survival benefit. In the future, prospective multi-center study is needed.

RADT-32. FREQUENT MULTIFOCAL INTRATUMORAL HEMORRHAGE IN MULTIPLE BRAIN METASTASES FROM HEPATOCELLULAR CARCINOMA

Abstract OBJECTIVE Brain metastasis (BM) rarely occurs in hepatocellular carcinoma (HCC); however, it frequently causes intratumoral hemorrhage (ITH). We investigated the clinical manifestations of ITH in patients with multiple BMs from HCC (HCC-BM). METHODS Patients who underwent treatment for multiple BMs with more than two metastatic sites were retrospectively reviewed and those diagnosed with HCC-BM were further analyzed. The multifocality of hemorrhage was classified into two groups, spatial and temporal multifocality, according to the radiological findings. The characteristics of multifocal hemorrhage in HCC were compared with those of BMs from other cancer types. RESULTS Fifteen out of 636 (2.36%) cases of multiple BMs were due to HCC metastasis. Out of 15 HCC-BM cases, 13 (86.7%) presented multifocal hemorrhage and 1 presented unifocal hemorrhage during the follow-up period. Spatial and temporal multifocality were observed in 9 and 5 cases, respectively, among 13 cases of multifocal hemorrhage. Among 636 cases of multiple BMs, HCC cases showed the highest frequency of multifocal hemorrhage, and HCC was significantly associated with multifocal hemorrhage compared with other primary-site cancer types (30/621 cases, 4.8%). Out of 15 patients with multiple HCC-BMs, 12 underwent whole-brain irradiation (WBI), and their median overall survival was 147 days. In one patient (8.3%), although treatment was stopped due to neurological deterioration by ITH, local BM control was favorable after the completion of WBI, and the only cause of death in six patients who completed WBI and were radiologically followed up until death was the progression of extracranial lesions. CONCLUSIONS Multiple HCC-BMs frequently present with multifocal ITH compared with BMs from other cancer types. Despite poor treatment outcome, WBI may show favorable local control considering the potential hemorrhagic event by tiny metastases that would not be detected radiologically. Immediate commencement of treatment before hemorrhage progression will be required for the treatment of multiple HCC-BMs.

Durable local control with hypofractionated radiation therapy for unresectable or metastatic melanoma

Background and purposeAs patients with advanced melanoma live longer in the context of systemic therapy advancements, better strategies for durable control of bulky tumors are needed. In this study, we evaluated if dose-escalated hypofractionated radiation therapy (HFRT) can provide durable local control and improve tumor-associated symptoms in patients with unresectable or bulky metastatic melanoma for whom stereotactic ablative radiotherapy (RT) approaches are not feasible due to tumor size or location. Materials and methodsWe retrospectively reviewed 49 patients with unresectable or bulky metastatic melanoma who were treated to a total of 53 tumor targets with 12–17 fractions HFRT at our institution between 2015–2022. Clinical scenarios included: unresectable, locoregional only disease (26 %); oligometastatic disease (<3 total sites, 17 %); oligoprogressive disease (<3 sites progressing, 17 %); and aggressive palliation (>5 known sites of disease or with at least 3 sites progressing, 40 %). ResultsOf the 53 HFRT targets, 91 % (n = 48) had radiographic evidence of response as defined by either stabilization (6 %, n = 3), decreased size (74 %, n = 39), or decreased FDG avidity (11 %, n = 6). Of the 43 symptomatic patients, 98 % (n = 42) had symptomatic improvement. One −year local control was 79 %, with 2-year progression-free and overall survival of 33 % and 39 % respectively. The most common acute toxicities were radiation dermatitis (16 %, n = 8) or a pain flare (14 %, n = 7). Late toxicities were uncommon and typically grade 1. ConclusionHFRT provides favorable local control and symptomatic relief with limited toxicity in tumors not amenable to surgical resection or stereotactic ablative RT.

Endoscopic submucosal dissection for lesions developing in the irradiated area of head and neck cancer.

Effective treatment of lesions that develop in the irradiated area of head and neck squamous cell carcinoma is a major concern. This study aimed to clarify the efficacy and safety of endoscopic resection for such lesions. Among consecutive patients who underwent endoscopic resection for histologically proven head and neck squamous cell carcinoma between January 2014 and December 2021, those who received definitive radiotherapy/chemoradiotherapy before endoscopic resection were included in this single-center, retrospective study. Short- and long-term outcomes were evaluated. Among 422 patients who underwent endoscopic resection for 615 lesions, 43 patients with 57 lesions were eligible. All 57 lesions were treated with endoscopic submucosal dissection and en bloc resection was achieved in all lesions. Grade 3 of Common Toxicity Criteria for Adverse Events v5.0 occurred in eight (19%) patients (dysphagia, seven; stricture, three; aspiration pneumonia, two; and pharyngeal necrosis, one [some cases overlapped]), but no grade ≥4 events occurred. Enteral nutrition by gastrostomy was temporarily required in two patients owing to dysphagia and laryngeal necrosis. During the median follow-up of 40 (interquartile range, 29.5-61) months after endoscopic submucosal dissection for the lesions developed in the irradiated area, local recurrence and metachronous lesions developed in two (5%) and nine (21%) patients, respectively. However, total laryngectomies and tracheostomies were avoided in all patients. The 3-year overall and disease-specific survivals were 81% (95% confidence interval, 64%-91%) and 94% (95% confidence interval, 79%-99%), respectively. Favorable local control and safety of endoscopic submucosal dissection were demonstrated.

Intra-arterial chemoradiotherapy for oral cancer: Superiority of intensity-modulated radiation therapy over three-dimensional conformal radiation therapy

PurposeTo determine the superiority of intensity-modulated radiation therapy (IMRT) over three-dimensional conformal radiation therapy (3DCRT) in patients who underwent intra-arterial chemoradiotherapy for oral cancer. MethodsWe retrospectively analyzed patients with locally advanced oral cancer curatively treated with intra-arterial chemoradiotherapy at a single institution between 2010 and 2021. All patients treated after May 2015 underwent IMRT. Docetaxel (12 mg/m2/week) and nedaplatin (5 mg/m2/day) were administered through a shallow temporal artery using a catheter. ResultsIn total, 143 patients (IMRT: 71; 3DCRT: 72) were included in this study. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 75.7 % and 59.8 %, respectively, with no significant differences between the irradiation methods. In multivariate analysis, cervical lymph node metastasis (LNM) was the only significant poor prognostic factor contributing to OS, PFS, locoregional control (LRC), and local control (LC). In multivariate subgroup analysis of LNM cases (n = 90), IMRT contributed to favorable LRC (hazard ratio [HR]=0.4, P = 0.01) and LC (HR=0.4, P = 0.006). There was no difference in the incidence of grade ≥2 osteonecrosis of the jaw (4.2 % vs. 12.5 %, P = 0.13), xerostomia (75 % vs. 82 %, P = 0.316), or dysgeusia (80 % vs. 82 %, P = 0.834) between the IMRT and 3DCRT groups. However, the rates of xerostomia at 6 months and dysgeusia at 3 months were lower in the IMRT group (both P < 0.001). ConclusionIMRT neither improved patient survival nor significantly reduced the incidence of osteonecrosis of the jaw. However, it demonstrated favorable LRC and LC in patients with LNM, suggesting an advantage in early recovery from xerostomia and dysgeusia.

Radiotherapy for Solitary Bony or Extramedullary Plasmacytoma.

This study aimed to determine the oncological outcomes associated with curative radiotherapy for solitary bony or extramedullary plasmacytomas by drawing on clinical data from a single tertiary center. This study aimed to provide a comprehensive understanding of the efficacy of radiotherapeutic interventions and delineate the patterns of disease recurrence. Eleven consecutive patients diagnosed with solitary bony or extramedullary plasmacytomas and treated between May 2007 and November 2023 were retrospectively screened. Different radiotherapy doses and fractionations were employed, and statistical analyses were performed to assess overall survival (OS) and disease-free survival (DFS). Among the 11 patients (9 males and 2 females), primary tumors were located within the bone in seven patients, whereas extramedullary tumors were observed in four patients. The median prescribed radiation dose was 46 Gy. The 5-year OS and DFS were 83.3% and 28.9%, respectively. Progression to multiple myeloma occurred in four patients with primary bony plasmacytoma. Local control rate was 88.9%, and one patient experienced distant metastasis after 32 months. Bony plasmacytoma has a high tendency of leading to multiple myeloma rather than extramedullary plasmacytoma (5-year progression to multiple myeloma-free survival rate, 20.8% vs. 100%, p=0.08). Radiotherapy is effective for solitary plasmacytomas with favorable local control and high objective response rates. A comparison with the existing literature supports the role of radiotherapy in the management of these conditions. The differences in outcomes between bony and extramedullary plasmacytomas emphasize the need for personalized treatment approaches.

Early signs of efficacy in patients with anti-PD-1 naïve and anti-PD-1 resistant HNSCC treated with NBTXR3/SBRT in combination with nivolumab or pembrolizumab in the phase I trial Study 1100.

6035 Background: Overcoming resistance to immune checkpoint inhibitors (ICIs) is a major clinical challenge. NBTXR3, a novel radioenhancer composed of functionalized hafnium oxide nanoparticles administered by a single intratumoral injection, locally amplifies radiotherapy (RT) dose without adding toxicity to surrounding healthy tissue. NBTXR3/RT enhances tumor cell death, tumor antigen release, and effectively expands T-cell repertoire in preclinical models, thus potentially triggering local and systemic immune responses to help improve ICI treatment. NBTXR3 has demonstrated favorable local control in pts with LA-HNSCC. Here we report early outcomes from the ongoing Study 1100 trial in pts with locoregionally recurrent (LRR) or metastatic (M+) head &amp; neck squamous cell carcinoma (HNSCC) who were either naïve to or who continued anti-PD-1 therapy combined with NBTRX3/RT after primary or secondary resistance to anti-PD-1 alone. Methods: A phase I dose escalation/expansion trial [NCT03589339] evaluating NBTXR3/Stereotactic Body RT (SBRT) followed by nivolumab or pembrolizumab in 3 cohorts of pts with advanced solid tumors. Pts have H&amp;N lesions either resistant to prior ICI or naïve, or lung, liver, or soft tissue metastases from ICI-resistant advanced solid tumors. SBRT doses were: HN 35 Gy/ 5 fxns; lung 45 Gy/ 5 fxns; liver 45 Gy/ 3 fxns; soft tissue as per investigator. Primary objective is safety of NBTXR3/RT/anti-PD-1 combination and its RP2D. Secondary objectives include efficacy. Results: The RP2D was 33%. There were 55 pts with HNSCC treated in the dose escalation/expansion parts. NBTXR3 injection was feasible and safe. There were 11pts (20%) who experienced G≥3 treatment related AEs, of which 3 pts experienced G≥3 AEs (5.5%) related to NBTXR3. Preliminary results of 33 pts, who were evaluable for efficacy: are reported. 6 pts with LRR disease: (2 ICI resistant, 4 naïve);. 27 pts with M+ disease (18 ICI resistant, 9 naïve). In ICI-resistant pts, objective tumor responses were observed in 25% (5/20), and the disease control rate (DCR) was 75% (15/20). In the ICI-naïve population, objective tumor responses were observed in 54% (7/13) of pts and DCR was 77% (10/13). There were observed improvements in injected lesions as well as in some noninjected target lesions. Updated efficacy data including OS in resistant and naïve pts will be presented. Conclusions: NBTXR3/RT/anti-PD-1 combination was feasible and well tolerated. Early data suggest the addition of NBTXR3/RT to ICI showed evidence of efficacy, including in patients who failed prior ICI, opening up an opportunity to further explore the ability of NBTXR3/RT to mitigate primary or secondary resistance to ICI. Clinical trial information: NCT03589339 .

Frameless LINAC Stereotactic Radiosurgery for Brain Metastasis using VMAT: A Review of 20 Cases and Institutional Experience

Background/Objectives: Brain metastases can be treated with Stereotactic Radiosurgery (SRS), a precise radiation therapy approach. This study aimed to review the feasibility and efficacy of frameless LINAC-based SRS using Volumetric Modulated Arc Therapy (VMAT) in a group of 20 patients. Methods: Twenty patients diagnosed with brain metastases received VMAT SRS. Clinical characteristics such as demographics, gender, performance status, number of brain metastases, neurological symptoms, neurosurgical procedures, systemic status, prior treatments, lesion size, SRS dose, local control after SRS and toxicity profile were assessed. Results: The median age of patients was 49.5 years (range 32-63), with 80% being female. Most patients (85%) had ECOG scores of 0-1. The median lesion size treated was 16 mm, with a median dose of 20 Gy for the first SRS (SRS1). After SRS1, 75% of patients achieved Local Control (LC), with a median duration of LC of 7.65 months. Six patients received a second SRS (SRS2) with a median dose of 20 Gy to a different location. Two out of six patients achieved LC after SRS2. Radiation necrosis occurred in 2 cases (10%). The median follow-up time from brain metastasis to the last follow-up was 20.31 months (range 0-50.43 months). Conclusion: Frameless LINAC-based VMAT SRS appears to be a promising treatment option for brain metastases. Initial findings suggest favorable local control rates and further research is needed to optimize treatment strategies.

Frameless LINAC Stereotactic Radiosurgery for Brain Metastasis using VMAT: A Review of 20 Cases and Institutional Experience

Background/Objectives: Brain metastases can be treated with Stereotactic Radiosurgery (SRS), a precise radiation therapy approach. This study aimed to review the feasibility and efficacy of frameless LINAC-based SRS using Volumetric Modulated Arc Therapy (VMAT) in a group of 20 patients. Methods: Twenty patients diagnosed with brain metastases received VMAT SRS. Clinical characteristics such as demographics, gender, performance status, number of brain metastases, neurological symptoms, neurosurgical procedures, systemic status, prior treatments, lesion size, SRS dose, local control after SRS and toxicity profile were assessed. Results: The median age of patients was 49.5 years (range 32-63), with 80% being female. Most patients (85%) had ECOG scores of 0-1. The median lesion size treated was 16 mm, with a median dose of 20 Gy for the first SRS (SRS1). After SRS1, 75% of patients achieved Local Control (LC), with a median duration of LC of 7.65 months. Six patients received a second SRS (SRS2) with a median dose of 20 Gy to a different location. Two out of six patients achieved LC after SRS2. Radiation necrosis occurred in 2 cases (10%). The median follow-up time from brain metastasis to the last follow-up was 20.31 months (range 0-50.43 months). Conclusion: Frameless LINAC-based VMAT SRS appears to be a promising treatment option for brain metastases. Initial findings suggest favorable local control rates and further research is needed to optimize treatment strategies.

Abstract PO1-22-09: Current margin assessment practice for breast-conserving surgery in China: a single institution audit

Abstract Background The appropriate negative margin width following breast-conserving surgery (BCS) for both ductal carcinoma in situ (DCIS) and invasive carcinoma (IC) has witnessed a shift towards de-escalation in international guidelines. However, there are limited nationwide data regarding margin assessment practice for BCS in China. This study aims to clarify the current real-world status of margin assessment from a single institution audit and secondarily to update the evidence on the association between margin width and local recurrence. Methods Eligible cases were derived from an extensive series of consecutive unselected patients with early invasive breast cancer who were treated with BCS at the Department of Breast Surgery in Shanghai Cancer Center Fudan University (FUSCC) between January 2015 and December 2017. Patient demographic and clinicopathological information as well as follow-up data were extracted from the hospital's electronic medical records. Pathological evaluation of negative margins was defined as no ink on tumor for IC in accordance with the SSO/ASTRO consensus guidelines released in 2014. Where applicable, margins were categorized as tumor on ink (involved), close margins (no tumor on ink but ≤1 mm), clear margins (1-2 mm), wide margins (2-5 mm), and wider margins (&amp;gt;5 mm). The positive margin rate (PMR), reoperation rate, and ipsilateral breast recurrence (IBR) rate were calculated according to different margin widths. Multivariable analyses of factors associated with re-excision were performed using binary logistic regression. Kaplan‒Meier survival curve analysis was performed for local recurrence-free survival (LRFS). Results A total of 2707 patients were enrolled in the current study, with a total PMR of 2.7%. The distribution of margin width revealed that wider margins (&amp;gt;5 mm) were optimized by most surgical oncologists (2092/2707, 77.3%) for BCS in our center. Additionally, the reoperation rates were 1.9% in the whole population, accounting for 48.3%, 7.5%, 4.2%, 0.8%, and 0.4% in each margin group. Specifically, among 247 patients with margins ≤2 mm, 41 (16.6%) received reoperation either by margin re-excision or mastectomy. Multivariable analyses identified that lobular histology, no selective additional resection and in situ pathology of involved/close margins are independent factors of re-excision recommendation. With a median follow-up of 54.3 months, the incidence of IBR was 1.7% in the whole cohort, representing for 5.2%, 4.2%, 2.8%, 1.9%, and 1.3% in each margin group, respectively. Kaplan‒Meier survival curve analysis showed a marginally significant difference in 5-year LRFS between groups with margins &amp;gt;2 mm and margins ≤2 mm (95.9% vs 97.8%, Table 1). Conclusions A wider margin width was preferably adopted in the routine practice of BCS. Our audit was aligned with previous evidence that a minimum clear margin of 2 mm is associated with a lower reoperation rate but favorable local control. Patients with margins no more than 2 mm were more likely to have re-excision in cases of lobular histology, no selective additional resection, and in situ pathology of involved/close margins. Ipsilateral breast recurrence models by margin status Citation Format: Feilin Qu, Cheng-Jia Shen, Wen-Tao Yang, Jun-Jie Li, Guangyu Liu, Zhi-Ming Shao. Current margin assessment practice for breast-conserving surgery in China: a single institution audit [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-22-09.

Salvage Ablative Radiotherapy for Isolated Local Recurrence of Pancreatic Adenocarcinoma following Definitive Surgery.

Introduction: The rate of isolated locoregional recurrence after surgery for pancreatic adenocarcinoma (PDAC) approaches 25%. Ablative radiation therapy (A-RT) has improved outcomes for locally advanced disease in the primary setting. We sought to evaluate the outcomes of salvage A-RT for isolated locoregional recurrence and examine the relationship between subsequent patterns of failure, radiation dose, and treatment volume. Methods: We conducted a retrospective analysis of all consecutive participants who underwent A-RT for an isolated locoregional recurrence of PDAC after prior surgery at our institution between 2016 and 2021. Treatment consisted of ablative dose (BED10 98-100 Gy) to the gross disease with an additional prophylactic low dose (BED10 < 50 Gy), with the elective volume covering a 1.5 cm isotropic expansion around the gross disease and the circumference of the involved vessels. Local and locoregional failure (LF and LRF, respectively) estimated by the cumulative incidence function with competing risks, distant metastasis-free and overall survival (DMFS and OS, respectively) estimated by the Kaplan-Meier method, and toxicities scored by CTCAE v5.0 are reported. Location of recurrence was mapped to the dose region on the initial radiation plan. Results: Among 65 participants (of whom two had two A-RT courses), the median age was 67 (range 37-87) years, 36 (55%) were male, and 53 (82%) had undergone pancreaticoduodenectomy with a median disease-free interval to locoregional recurrence of 16 (range, 6-71) months. Twenty-seven participants (42%) received chemotherapy prior to A-RT. With a median follow-up of 35 months (95%CI, 26-56 months) from diagnosis of recurrence, 24-month OS and DMFS were 57% (95%CI, 46-72%) and 22% (95%CI, 14-37%), respectively, while 24-month cumulative incidence of in-field LF and total LRF were 28% (95%CI, 17-40%) and 36% (95%CI 24-48%), respectively. First failure after A-RT was distant in 35 patients (53.8%), locoregional in 12 patients (18.5%), and synchronous distant and locoregional in 10 patients (15.4%). Most locoregional failures occurred in elective low-dose volumes. Acute and chronic grade 3-4 toxicities were noted in 1 (1.5%) and 5 patients (7.5%), respectively. Conclusions: Salvage A-RT achieves favorable OS and local control outcomes in participants with an isolated locoregional recurrence of PDAC after surgical resection. Consideration should be given to extending high-dose fields to include adjacent segments of at-risk vessels beyond direct contact with the gross disease.

Monocentric Retrospective Study: Efficacy, Feasibility, and Prognostic Factors of Single-Insertion High-Dose-Rate Brachytherapy With 4 Sessions for Locally Advanced Cervical Cancer

ObjectiveThis study aims to assess the feasibility and efficacy of high-dose-rate (HDR) brachytherapy (BT) administered in a single insertion with four treatment sessions for locally advanced cervical cancer (LACC), and to identify the prognostic factors influencing outcomes. MethodsWe retrospectively analyzed the clinical data of cervical cancer patients with locally advanced disease (International Federation of Gynecology and Obstetrics 2018 (FIGO) IB-IVB), treated at our institution from January 2014 through December 2021. Each patient received definitive radiotherapy with an external irradiation dosage between 45-50.4 Gy along with concurrent chemotherapy (CCRT). HDR-BT (24 Gy) was prescribed to a high-risk clinical target volume (HR-CTV). Results139 patients were included and HDR-BT program could be fully performed in 136 patients (98%). Over a median follow-up duration of 40.5 months, the two-year local control (LC), overall survival (OS), and disease-free survival (DFS) rates stood at 79.4%, 77.7%, and 61.7% respectively, with five-year rates at 78.2%, 61.6%, and 55.7%. Multivariate analysis revealed the primary determinant of LC as the tumor's response to external beam radiotherapy (EBRT) as determined via magnetic resonance imaging (MRI) prior to BT. Parametrial involvement demonstrated a significant multivariate association with DFS (p = 0.04). Regarding OS, parametrial invasion (p = 0.01) and the tumor's response post-chemoradiotherapy (p = 0.02) emerged as significant factors. Regarding chronic toxicities, 18% (25 patients) experienced grade 3 complications. An optimal D2cc (Bowel) threshold of 70 Gy (p = 0.001) was identified to limit chronic digestive complications of grade 3 or higher. ConclusionThe implementation of single-insertion, four-session HDR-BT could be performed in 98% of the patients. It yields favorable LC and OS rates, coupled with tolerable toxicity in patients with LACC. Response to initial chemoradiotherapy evaluated on pre-BT MRI is an important prognostic factor and could help to individualized therapeutic strategies.

Assessment of minimum target dose as a predictor of local failure after spine SBRT

ObjectivesMetastasis-directed stereotactic body radiation therapy (SBRT) has demonstrated robust clinical benefits in carefully selected patients, improving local control and even overall survival (OS). We assess a large database to determine clinical and dosimetric predictors of local failure after spine SBRT. MethodsSpine SBRT treatments with imaging follow-up were identified. Patients were treated with a simultaneous integrated boost technique using 1 or 3 fractions, delivering 20–24 Gy in 1 fraction to the gross tumor volume (GTV) and 16 Gy to the low dose volume (or 27–36 Gy and 21–24 Gy for 3 fraction treatments). Exclusions included: lack of imaging follow-up, proton therapy, and benign primary histologies. Results522 eligible spine SBRT treatments (68 % single fraction) were identified in 377 unique patients. Patients had a median OS of 43.7 months (95 % confidence interval: 34.3–54.4). The cumulative incidence of local failure was 10.5 % (7.4–13.4) at 1 year and 16.3 % (12.6–19.9) at 2 years. Local control was maximized at 15.3 Gy minimum dose for single-fraction treatment (HR = 0.31, 95 % CI: 0.17 – 0.56, p < 0.0001) and confirmed via multivariable analyses. Cumulative incidence of local failure was 6.1 % (2.6–9.4) vs. 14.2 % (8.3–19.8) at 1 year using this cut-off, with comparable findings for minimum 14 Gy. Additionally, epidural and soft tissue involvement were predictive of local failure (HR = 1.77 and 2.30). ConclusionsSpine SBRT offers favorable local control; however, minimum dose to the GTV has a strong association with local control. Achieving GTV minimum dose of 14–15.3 Gy with single fraction SBRT is recommended whenever possible.

Results of Definitive (Chemo)radiotherapy Using Computed Tomography-based Brachytherapy for Cervical Cancer.

Concurrent cisplatin-based chemoradiotherapy (CCRT) is the standard treatment for locally advanced cervical cancer. Especially, CCRT with magnetic resonance imaging (MRI) or computed tomography-based image-guided brachytherapy (CT-based 3D-IGBT) for cervical cancer has resulted in good LC rates. However, progression-free survival (PFS) and overall survival (OS) rates for locally advanced cervical cancer are still low and could be improved. The aim of the study was to evaluate treatment efficacy and late toxicity of external beam radiotherapy (EBRT) and CT-based IGBT with or without concurrent chemotherapy in patients with squamous cell carcinoma of the uterine cervix and investigate patterns of failure. We retrospectively analyzed clinical data of cervical squamous cell carcinoma patients treated with definitive radiotherapy with or without concurrent chemotherapy at Saitama Medical University International Medical Center. Local control (LC), PFS, patterns of failure, and late toxicity were the evaluated outcomes. Overall, 290 patients were enrolled in the study. Median follow-up was 51.5 months. During follow-up, 74 patients developed recurrence: 10 patients with intra-pelvic failure only, 45 with extra-pelvic failure only, and 19 with both. The 3-year LC was 100% for T1b-T2a, 96.8% for T2b, 89.5% for T3b, and 88.5% for T4 disease. The 3-year PFS was 100% for stage IB-IIA, 89.0% for stage IIB, 70.7% for stage IIIB, 72.6% for stage IIIC1r, and 40.1% for stage IVA. The incidence of grade 3-4 gastrointestinal and genitourinary toxicities was 3.0% and 1.7%, respectively. Combination of EBRT and CT-based IGBT with or without concurrent chemotherapy produced favorable LC with acceptable rates of late toxicities. However, extra-pelvic failures frequently occurred and PFS was less satisfactory in patients with stage III-IVA disease, which indicated the need for additional treatment in these patients.

Carbon-ion radiotherapy for hepatocellular carcinoma with major vascular invasion: a retrospective cohort study

BackgroundMacroscopic vascular invasion (MVI) significantly impacts survival in patients with hepatocellular carcinoma (HCC), warranting systemic therapy over locoregional therapy. Despite novel approaches, HCC with MVI has a poor prognosis compared to early-to intermediate-stage HCC. This study aimed to evaluate the safety and efficacy of carbon-ion radiotherapy (C-ion RT) for HCC characterized by MVI.MethodsThis retrospective cohort study evaluated HCC patients with MVI treated using C-ion RT with a dose of 45.0–48.0 Gy/2 fractions or 52.8–60.0 Gy/4 fractions between 1995 and 2020 at our institution in Japan. We analyzed the prognostic factors and rates of local recurrence, survival, and adverse events. The local recurrence rate was determined using the cumulative incidence function, with death as a competing event. Survival rates were determined using the Kaplan–Meier method. The log-rank test for univariate analysis and the Cox proportional hazards model for multivariate analysis were used to compare subgroups.ResultsIn total, 76 patients with a median age of 71 years (range, 45–86 years) were evaluated. Among them, 68 had Child–Pugh grade A while eight had grade B disease. In 17 patients, the vascular tumor thrombus reached the inferior vena cava or main trunk of the portal vein. Over a median follow-up period of 27.9 months (range, 1.5–180.4 months), the 2-year overall survival, progression-free survival, and local recurrence rates were 70.0% (95% confidence interval [CI]: 57.7–79.4%), 32.7% (95% CI: 22.0–43.8%), and 8.9% (95% CI: 1.7–23.5%), respectively. A naïve tumor and a single lesion were significant prognostic factors for overall survival in the univariate analysis. Albumin-bilirubin grade 1 and a single lesion were independent prognostic factors in the multivariate analysis. Overall, four patients (5%) experienced grade 3 late adverse events, with no observed grade 4 or 5 acute or late adverse events.ConclusionsC-ion RT for HCC with MVI showed favorable local control and survival benefits with minimal toxicity.

Outcome After Modern Proton Beam Therapy in Childhood Craniopharyngioma: Results of the Prospective Registry Study KiProReg

BackgroundCraniopharyngiomas (CPs) are rare tumours of the sellar region often leading to significant comorbidities due to their close proximity to critical structures. Aim of this study was to analyse survival outcome and late toxicities after surgery and proton beam therapy (PBT) in childhood CPs. Patients and methodsWithin the prospective XXXX study (XXXX), data of 74 childhood patients with CP, receiving PBT between 08/2013-06/2022 were eligible. Late toxicities were analysed according to the grading system of CTCAE 4.0. Results: Median follow-up (FU) since first diagnosis was 4.3 years (range, 0.8-14.7). 75.7% of patients received PBT at time of disease progression or recurrence, whereas 24.3% as part of their primary therapy (definitive or adjuvant). Predominantly (85.1%), pencil beam scanning technique was used. Median total dose and initial tumour volume were 5400 cGyRBE (relative biological effectiveness) and 17.64 cm³ (range, 3.07-300.59), respectively. The estimated (±SE) 3-year overall survival, progression-free and cystic failure-free survival rate after PBT were 98.2% (±1.7), 94.7% (±3.0), and 76.8% (±5.4), respectively. All local failures (n=3) were in-field relapses necessitating intervention and occurred exclusively in patients receiving PBT at progression or recurrence. Early cystic enlargements after PBT were typically asymptomatic and self-limiting. Fatigue, headaches, vision disorders, obesity and endocrinopathies were the predominant late toxicities. No high grade (≥3) new-onset visual impairment or cognitive deterioration occurred compared to baseline. The presence of cognitive impairments at the end of FU correlated with size of the planning target volume (p=0.034), Dmean dose to the temporal lobes (p=0.032,p=0.045) and the number of surgical interventions prior to PBT (p=0.029). Conclusions: Our findings demonstrate favourable local control rates using modern PBT with acceptable late toxicities. Cyst growth within 12 month after radiotherapy is typically not associated with tumour progression. Longer FU has to be awaited to confirm results.

Role of stereotactic radiosurgery for recurrent skull base acinic cell carcinoma: illustrative case.

Acinic cell carcinomas (AcCCs), rare malignancies of the salivary glands, often recur and metastasize, particularly in the skull base. Conventional radical resection can be invasive for skull base AcCCs adjacent to cranial nerves and major vasculature, and the effectiveness of stereotactic radiosurgery (SRS) as an alternative is not well established. This case report details the application of SRS for recurrent skull base AcCCs. A 71-year-old male with a history of resection for a right mandibular AcCC 23 years earlier experienced tumor recurrence involving the right cavernous sinus and nasal cavity. He underwent endoscopic transnasal surgery followed by SRS targeting different tumor locations-the cavernous sinus to the pterygopalatine fossa, maxillary sinus, and clivus-each with a prescribed dose of 20 Gy to the 40% to 50% isodose line. After the first skull base metastasis, additional sessions of localized SRS after endoscopic surgery led to a 12-year survival without sequela. This is a report indicating that SRS for skull base AcCCs can achieve favorable local control, functional preservation, and long-term survival. SRS may be suitable for skull base AcCC given the lesion's tendency toward multiple local recurrences. Further investigation is needed to validate the treatment's efficacy.

The individualized delineation of clinical target volume for primary nasopharyngeal carcinoma based on invasion risk of substructures: A prospective, real-world study with a large population

Background and purposeThe delineation of clinical target volume (CTV) for primary nasopharyngeal carcinoma (NPC) is currently controversial and the international guideline still recommend a uniform border for CTV regardless of the tumor extent. We conducted this prospective, real-world study to evaluate the clinical outcomes of our individualized CTV delineation method based on distance plus substructures. Materials and MethodsWe preliminarily investigated the local extension patterns of NPC on 354 newly diagnosed patients and defined the structures surrounding the nasopharynx as Level-1 to Level-4 substructures stratified by the risk of invasion. We then enrolled patients with newly diagnosed NPC without distant metastasis to investigate our individualized CTV delineation protocol. All patients received intensity modulated radiotherapy. CTV1 and CTV2 were prescribed doses of 60 Gy and 54 Gy in 30 ∼ 33 fractions. The primary endpoint was local recurrence-free survival (LRFS); secondary endpoints included regional control and survival, estimated using the Kaplan-Meier method. The local failure patterns were also analyzed. ResultsFrom January 2008 to December 2012 and from January 2013 to September 2019, 356 and 648 patients were enrolled, named as training set and validation set, respectively. With a median follow-up of 104.6 (interquartile, 73.1–126.9) and 51.4 (39.5–78.5) months, 31 (8.7 %) and 38 (5.9 %) patients in training and validation sets experienced local recurrence, and the 5-year LRFS was 93.0 % and 93.2 %, respectively; 63 (17.7 %) and 39 (6 %) patients died in training and validation sets, and the 5-year overall survival (OS) was 88.5 % and 93.4 %, respectively. For the whole study cohort (N = 1004) with a median follow-up of 66.6 (41.5–98.0) months, the 5-year LRFS and OS was 93.2 % and 91.5 %. The grade 3 late toxicities included xerostomia, subcutaneous fibrosis, hearing impairment, trismus, visuality impairment and skin atrophy, with a total incidence of 1.5 %. Sixty-seven of 69 (97.1 %) local recurrence was in high-dose area. ConclusionOur individualized CTV delineation method can achieve favorable local tumor control and long-term survival outcomes with acceptable late toxicities.

Interferon alpha 2b or Mitomycin-C as Adjuvant Therapy of Pigmented Conjunctival Malignancy : A Literature Review

Abstract&#x0D; Introduction &amp; Objectives : To compare the efficacy and safety between Mitomycin C (MMC) and Interferon alpha-2b (IFN-α2b) eye drops as adjuvant therapy for conjunctival melanoma.&#x0D; Methods : Literature searching was conducted using PubMed, ScienceDirect, and Google Scholar. All studies that met the inclusion and exclusion criteria were categorized based on the level of evidence. The data of patients demographics, staging of disease, type of treatments, and outcomes of this review including local control rate, side effect, and recurrence and/or metastases were also reported.&#x0D; Results : From twelve articles, topical adjuvant chemotherapy with MMC and IFN α-2b showed favourable complete remission rate. Local control (complete remission) of IFN α-2b group is 46%, while in MMC group is 57%. The most side effect of MMC group were severe corneal-conjunctival irritation and corneal defect, while the IFN α-2b group showed mild side effect. Recurrency rate of IFN α-2b group and MMC group both is 35%. Metastases case of IFN α-2b group is 3.8%, while none of cases from MMC group metastases.&#x0D; Conclusion : Topical adjuvant chemotherapy with MMC and IFN α-2b showed favourable local control rate even though the recurrency rate also relatively high. Both medications showed promising results to reduce residual tumor size after wide excision surgery, preserving eye so reduce the chance of exenteration in various stages. It is important to consider adjuvant therapy following wide excision surgery as the first line treatment.

GammaTile® (GT) as a brachytherapy platform for rapidly proliferating glioblastomas: from case series to clinical trials.

Radiation plays a central role in glioblastoma treatment. Logistics related to coordinating clinic visits, radiation planning, and surgical recovery necessitate delay in radiation delivery from the time of diagnosis. Unimpeded tumor growth occurs during this period, and is associated with poor clinical outcome. Here we provide a pilot experience of GammaTile ® (GT), a collagen tile-embedded Cesium-131 (131Cs) brachytherapy platform for such aggressive tumors. We prospectively followed seven consecutive patients (2019-2023) with newly diagnosed (n = 3) or recurrent (n = 4) isocitrate dehydrogenase wild-type glioblastoma that grew > 100% in volume during the 30days between the time of initial diagnosis/surgery and the radiation planning MRI. These patients underwent re-resection followed by GT placement. There were no surgical complications. One patient developed right hemiparesis prior to re-resection/GT placement and was discharged to rehabilitation, all others were discharged home-with a median hospital stay of 2days (range: 1-5days). There was no 30-day mortality and one 30-day readmission (hydrocephalus, requiring ventriculoperitoneal shunting (14%)). With a median follow-up of 347days (11.6months), median progression free survival of ≥ 320days (10.6months) was achieved for both newly and recurrent glioblastoma patients. The median overall survival (mOS) was 304 and 347days (10 and 11.5 mo) for recurrent and newly diagnosed glioblastoma patients, respectively. Our pilot experience suggests that GT offers favorable local control and safety profile for patients afflicted with rapidly proliferating glioblastomas and lay the foundation for future clinical trial design.