Tumor Control Outcomes Research Articles

Stereotactic radiosurgery for fourth ventricle brain metastases: tumor control outcomes and the need for CSF diversion. Patient series.

Stereotactic radiosurgery is a favorable alternative to surgery for intracranial cerebral metastases. Fourth ventricle (V4) metastases are challenging because of the location and surrounding structures, with a high risk for obstructive hydrocephalus and brainstem compression. Here, the authors evaluate the effectiveness in terms of safety, tumor control rates, and permanent cerebrospinal fluid (CSF) diversion of primary Gamma Knife radiosurgery (GKRS) in treating V4 metastases. Eleven of 1060 patients had V4 brain metastases. No patients had pre-GKRS hydrocephalus. The mean tumor volume was 3.3 cm3, treatment dose was 18 Gy to the 50.5% isodose line (average 14 shots), conformity index was 1.4, and volume of brainstem receiving greater than 12 Gy was 0.2 cm3. Eight patients had radiographic and clinical follow-ups. The average time to initial follow-up was 3.1 months. Karnofsy Performance Status did not change from the initial consultation to the post-GKRS follow-up. No patients developed hydrocephalus or required permanent CSF diversion. One patient required transient external ventricular drain placement; however, neurological symptoms resolved with steroid therapy. Seven patients received steroid therapy post-GKRS. Seven patients had radiographic disease control at the 6-month follow-up. One patient had tumor progression at 6 months and underwent surgery. Primary GKRS for V4 metastases with a close follow-up is safe and optimizes quality of life for patients with significant cancer burden. https://thejns.org/doi/10.3171/CASE24293.

Limitations of outcome prediction based on interfractional volume changes of large (≥ 10cm3) brain metastases during fractionated gamma knife radiosurgery.

This study investigated the interfractional volume changes of large (≥ 10 cm3) brain metastases (BMs) during fractionated gamma knife radiosurgery (FGKRS) to assess its predictive value for tumor control outcomes. The patients who underwent FGKRS for large BMs between January 2017 and December 2022 in our center were reviewed. The interfractional volume change was defined as the disparity in tumor volume (TV) measured between the magnetic resonance images acquired on the first treatment day and those obtained after 2 or 3 fractions during the course of FGKRS. A total of 73 lesions in 70 patients with various primary pathologies were included. Over a median follow-up period of 11months (range 1-77), the tumor control rate was 63%. Initial TV (cm3) was associated with progression free survival (PFS) and overall survival (OS) in both univariate and multivariate analyses (p = 0.01). Interfractional TV changes revealed an increase in 13 (17.8%) lesions, no change in 14 (19.2%) lesions, and a decrease in 46 (63.0%) lesions, with a mean volume reduction of 5% ± 0.12. Three cut-offs (5%, 10% and 15% volume decrement) were established and patients were divided into two groups based on each reference point. However, there were no significant differences in PFS and OS between the two groups, irrespective of the chosen cut-off value used. Interfractional volume changes of large BMs were not found to be associated with tumor control outcomes. Neither significant interfractional volume reduction nor significant volume increase necessarily predicts the tumor control, making early close monitoring essential after FGKRS.

3D small-scale dosimetry and tumor control of 225Ac radiopharmaceuticals for prostate cancer

Radiopharmaceutical therapy using α\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\upalpha$$\\end{document}-emitting 225\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{225}$$\\end{document}Ac is an emerging treatment for patients with advanced metastatic cancers. Measurement of the spatial dose distribution in organs and tumors is needed to inform treatment dose prescription and reduce off-target toxicity, at not only organ but also sub-organ scales. Digital autoradiography with α\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\upalpha$$\\end{document}-sensitive detection devices can measure radioactivity distributions at 20–40 μm\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\upmu {\\hbox {m}}$$\\end{document} resolution, but anatomical characterization is typically limited to 2D. We collected digital autoradiographs across whole tissues to generate 3D dose volumes and used them to evaluate the simultaneous tumor control and regional kidney dosimetry of a novel therapeutic radiopharmaceutical for prostate cancer, [225Ac]Ac-Macropa-PEG4-YS5, in mice. 22Rv1 xenograft-bearing mice treated with 18.5 kBq of [225Ac]Ac-Macropa-PEG4-YS5 were sacrificed at 24 h and 168 h post-injection for quantitative α\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\upalpha$$\\end{document}-particle digital autoradiography and hematoxylin and eosin staining. Gamma-ray spectroscopy of biodistribution data was used to determine temporal dynamics and 213\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{213}$$\\end{document}Bi redistribution. Tumor control probability and sub-kidney dosimetry were assessed. Heterogeneous 225\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{225}$$\\end{document}Ac spatial distribution was observed in both tumors and kidneys. Tumor control was maintained despite heterogeneity if cold spots coincided with necrotic regions. 225\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{225}$$\\end{document}Ac dose-rate was highest in the cortex and renal vasculature. Extrapolation of tumor control suggested that kidney absorbed dose could be reduced by 41% while maintaining 90% TCP. The 3D dosimetry methods described allow for whole tumor and organ dose measurements following 225\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{225}$$\\end{document}Ac radiopharmaceutical therapy, which correlate to tumor control and toxicity outcomes.

Advances in clinical research on ultrasound-guided radiofrequency ablation for papillary thyroid microcarcinoma.

Ultrasound-guided radiofrequency ablation (RFA) emerges as a minimally invasive strategy for papillary thyroid microcarcinoma (PTMC), offering advantages over traditional surgical approaches. RFA employs high-frequency electric currents under precise ultrasound guidance to ablate cancerous tissue. Clinical trials consistently demonstrate RFA's efficacy in tumor control and patient-reported outcomes. However, long-term studies are essential to validate its durability and monitor for potential complications. Collaborative efforts among various medical disciplines ensure procedural accuracy and comprehensive postoperative care. Technological innovations, such as enhanced ultrasound imaging and temperature control, promise to refine RFA's precision and effectiveness. Nevertheless, challenges persist, including the need for standardized protocols and comparative studies with traditional treatments. Future research should focus on long-term outcomes, patient selection criteria, and optimization of procedural techniques to solidify RFA's role in PTMC management. RFA presents a promising avenue for PTMC treatment, warranting further investigation and refinement in clinical practice.

Radiation Therapy Dose Response in Bulky Relapsed/Refractory Large B-Cell Lymphoma

PurposeTo assess whether a radiotherapy (RT) dose affects response in bulky tumors in relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL). MethodsData from r/r DLBCL patients treated with salvage- or palliative-intent RT (2008-2020) at a single institution were examined. Index lesion size ≥7.5 cm was defined as bulky. Equivalent doses in 2 Gray (Gy) fractions (EQD2) were calculated to compare doses between conventional and hypofractionated (HF, ≥2.5 Gy/fraction) schemes. Objective response rates (ORR) were compared using non-parametric Mann-Whitney U test or Kruskal-Wallis tests with Dunn's multiple comparison corrections. Freedom from local progression (FFLP) was assessed using Kaplan-Meier and Cox proportional hazard regression analyzes. Results183 courses of 151 unique patients were included (salvage: 37%, palliative: 63%). Non-bulky and bulky tumors were irradiated in 109 (60%) and 74 (40%) courses, respectively. Median EQD2 was 33 Gy (IQR=23-39 Gy) with HF in 84 (46%) cases. Of those with post-RT imaging (80%), the ORR was 59% with a trend towards worsened ORR in bulky tumors (50% vs. 65%, p=0.077). For bulky tumors, RT regimens with EQD2s >30 Gy were associated with better ORR (≤30 Gy vs. >30 Gy: 27% vs. 64%, p=0.0073), whereas a lower EQD2 cut-off was sufficient for non-bulky tumors (≤20 Gy vs. >20 Gy: 38% vs. 75%, p=0.0011). On multivariable regression, bulky tumor size was associated with worsened FFLP (HR=2.07, 95% CI=1.16-3.68, p=0.014), while high EQD2s >30 Gy were associated with better FFLP (HR=0.48, 95% CI=0.25-0.93, p=0.031). Bulky tumors treated with EQD2s ≤30 Gy had the lowest median FFLP (4.0 months), while EQD2s >30 Gy had an unreached median FFLP (p=0.0047). ConclusionsBulky r/r DLBCL tumors were associated with less favorable tumor control outcomes in the salvage and palliative settings. RT regimens with higher EQD2s (>30 Gy) should be considered if durable local control of bulky tumors is desired.

Pleomorphic Xanthoastrocytoma: Multi-Institutional Evaluation of Stereotactic Radiosurgery

BACKGROUND AND OBJECTIVES: Pleomorphic xanthoastrocytoma (PXA) is a rare low-grade glial tumor primarily affecting young individuals. Surgery is the primary treatment option; however, managing residual/recurrent tumors remains uncertain. This international multi-institutional study retrospectively assessed the use of stereotactic radiosurgery (SRS) for PXA. METHODS: A total of 36 PXA patients (53 tumors) treated at 11 institutions between 1996 and 2023 were analyzed. Data included demographics, clinical variables, SRS parameters, tumor control, and clinical outcomes. Kaplan-Meier estimates summarized the local control (LC), progression-free survival, and overall survival (OS). Secondary end points addressed adverse radiation effects and the risk of malignant transformation. Cox regression analysis was used. RESULTS: A total of 38 tumors were grade 2, and 15 tumors were grade 3. Nine patients underwent initial gross total resection, and 10 received adjuvant therapy. The main reason for SRS was residual tumors (41.5%). The median follow-up was 34 months (range, 2-324 months). LC was achieved in 77.4% of tumors, with 6-month, 1-year, and 2-year LC estimates at 86.7%, 82.3%, and 77.8%, respectively. Younger age at SRS (hazard ratios [HR] 3.164), absence of peritumoral edema (HR 4.685), and higher marginal dose (HR 6.190) were significantly associated with better LC. OS estimates at 1, 2, and 5 years were 86%, 74%, and 49.3%, respectively, with a median OS of 44 months. Four patients died due to disease progression. Radiological adverse radiation effects included edema (n = 8) and hemorrhagic change (n = 1). One grade 3 PXA transformed into glioblastoma 13 months after SRS. CONCLUSION: SRS offers promising outcomes for PXA management, providing effective LC, reasonable progression-free survival, and minimal adverse events.

Outcomes of Near-Total and Subtotal Resection of Sporadic Vestibular Schwannoma: A Systematic Review and Meta-Analysis.

To evaluate tumor control and facial nerve outcomes after gross-total (GTR), near-total (NTR), and subtotal resection (STR) of sporadic vestibular schwannomas (VS). PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus databases were searched in August 2021 through inception following PRISMA guidelines. English language articles reporting tumor control and facial nerve outcomes of adults (≥18 years) with NTR and STR of VS were evaluated. Study characteristics, demographics data, tumor characteristics, type of surgical intervention, and outcome measures on tumor control and facial nerve function were collected. Pooled relative risk (RR) estimates for tumor recurrence and facial nerve outcomes were calculated and stratified by extent of resection. From an initial search of 2504 articles, 48 studies were included in the analysis. When comparing 1108 patients who underwent NTR to 3349 patients with GTR, the pooled RR of recurrence in the NTR cohort was 2.94 (95% confidence interval [CI] 1.65-5.24, P = .0002). When comparing 1016 patients who underwent STR to 6171 patients with GTR, the pooled RR of recurrence in the STR cohort was 11.50 (95% CI 6.64-19.92, P < .0001). Estimates for risk of tumor regrowth for less-than-complete resection are presented. There was no elevated risk of adverse facial nerve outcome (defined as House-Brackmann grade III and above) in each category of extent of resection compared to GTR. Extent of resection predicts risk of tumor recurrence/regrowth following microsurgical resection. Favorable facial nerve outcome should be weighed against the increased risk of regrowth and the potential need for further treatment.

Long-Term Outcomes and Survival Rates of Patients Undergoing Biopsy Vs. Maximum Safe Resection for Thalamic Lesions: A Short Review on Current Evidence

The thalamic lesion is one of the most challenging tumors with significant mortality and morbidities. Current literature highlights the importance of individualized treatment strategies tailored to the specific characteristics of the lesion and the patient. In terms of efficacy, studies have demonstrated that maximal safe resection (MSR) of thalamic lesions can lead to better tumor control, prolonged progression-free survival, and improved overall survival rates compared to biopsy alone. However, the feasibility of achieving MSR is highly dependent on the location, size, and histology of the lesion, as well as the patient's functional status and overall health. Also, surgical interventions in the thalamus carry inherent risks of neurological deficits, including sensory, motor, and cognitive impairments, depending on the extent of surgical resection and proximity to eloquent neural structures. On the other hand, biopsy remains a valuable diagnostic tool for obtaining tissue samples and establishing a definitive histological diagnosis in cases where MSR is not feasible or poses a high risk of neurological complications. Indeed, biopsy is preferred in patients with advanced age, significant comorbidities, or lesions located in eloquent regions of the thalamus where aggressive surgical resection may result in considerable morbidity. Quality of life (QoL) outcomes, including functional status, symptom burden, and overall well-being, are important endpoints in evaluating the impact of treatment approaches for thalamic lesions on patients' daily activities. While MSR may offer potential long-term benefits in terms of tumor control and survival outcomes, it may also be associated with a higher risk of neurological deficits and functional impairments that can impact QoL postoperatively. Conversely, biopsy may involve less invasive procedures and shorter recovery times, resulting in better preserved functional status and improved QoL in selected patient populations.

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.

Risk-benefit analysis of surgical treatment strategies for cystic craniopharyngioma in children and adolescents.

Treatment strategies for craniopharyngiomas are still under debate particularly for the young population. We here present tumor control and functional outcome data after surgical treatment focusing on stereotactic and microsurgical procedures for cystic craniopharyngiomas in children and adolescents. From our prospective institutional database, we identified all consecutive patients less than 18 years of age who were surgically treated for newly-diagnosed cystic craniopharyngioma between, 2000 and, 2022. Treatment decisions in favor of stereotactic treatment (STX) or microsurgery were made interdisciplinary. STX included aspiration and/or implantation of an internal shunt catheter for permanent cyst drainage. Microsurgery aimed for safe maximal tumor resections. Study endpoints were time to tumor recurrence (TTR) and functional outcome including ophthalmological/perimetric, endocrinological, and body-mass index (BMI) data. 29 patients (median age 9.9 yrs, range 4-18 years) were analyzed. According to our interdisciplinary tumor board recommendation, 9 patients underwent stereotactic treatment, 10 patients microsurgical resection, and 10 patients the combination of both. Significant volume reduction was particularly achieved in the stereotactic (p=0.0019) and combined subgroups (p<0.001). Improvement of preoperative visual deficits was always achieved independent of the applied treatment modality. Microsurgery and the combinational treatment were associated with higher rates of postoperative endocrinological dysfunction (p<0.0001) including hypothalamic obesity (median BMI increase from 17.9kg/m2 to 24.1kg/m2, p=0.019). Median follow-up for all patients was 93.9 months (range 3.2-321.5 months). Recurrent tumors were seen in 48.3% and particularly concerned patients after initial combination of surgery and STX (p=0.004). In here, TTR was 35.1 ± 46.9 months. Additional radiation therapy was found indicated in 4 patients to achieve long-lasting tumor control. In children and adolescents suffering from predominantly cystic craniopharyngiomas, stereotactic and microsurgical procedures can improve clinical symptoms at low procedural risk. Microsurgery, however, bears a higher risk of postoperative endocrine dysfunction. A risk-adapted surgical treatment concept may have to be applied repeatedly in order to achieve long-term tumor control even without additional irradiation.

Does cryotherapy decrease the local recurrence rate in the treatment of an aneurysmal bone cyst? A comparative assessment.

Curettage with or without the use of adjuvants is the standard of care in the treatment of an aneurysmal bone cyst (ABC). Historically, our approach combined curettage, high-speed burr drilling, and cryoablation. However, treatments varied based on age, tumor location, and surgeon preference. We asked: (1) Does cryoablation in addition to curettage and burr drilling decrease the local recurrence rates? (2) Are there any risk factors for the local recurrence rate? (3) Does cryoablation improve postsurgical functional outcomes in these patients? Patients treated for an ABC, between January 2006 and December 2019 were included in this retrospective analysis. Patient and surgical characteristics, such as age, gender, tumor location, type of treatment, time of follow-up, recurrence rate, and functional outcome measured by the Musculoskeletal Tumor Society Score 1993 (MSTS93) score were compared between those treated with and without cryoablation. Both groups, without cryoablation (n = 88) and with cryoablation (n = 42), showed no significant difference in local recurrence rates (9.1% vs. 7.1%, p = 0.553) and functional outcomes as measured by the MSTS93 score (28.9 vs. 27.8, p = 0.262). Risk factors analyzed did not significantly affect local recurrence risk, except for secondary ABC diagnosis (p = 0.017). The cryoablation group had a more extended follow-up (45.6 vs. 73.2 months, p < 0.001), reflecting a shift in practice over time. We found no significant difference in local recurrence rate or functional outcome in patients treated with or without cryoablation. Formal curettage with additional high-speed burr drilling provides effective tumor control and favorable functional outcomes, negating the need for adjuvant cryoablation.

Whole-brain radiation therapy plus simultaneous integrated boost for brain metastases from breast cancers.

The effect of whole-brain radiation therapy (WBRT) plus simultaneous integrated boost (SIB) in brain metastasis from breast cancers has not been demonstrated. In this single-center retrospective study, we reviewed consecutive breast cancer patients who developed brain metastasis and were treated with hypofractionated radiation therapy plus WBRT using intensity-modulated radiation therapy (IMRT)-SIB approaches. We analyzed clinical outcomes, prognostic factors and patterns of treatment failure. A total of 27 patients were eligible for analysis. Four (14.8%) patients achieved clinical complete response and 14 (51.9%) had partial response of brain lesions. The other nine patients were not evaluated for brain tumor response. The median brain progression-free survival was 8.60 (95% CI [6.43-13.33]) months and the median overall survival was 16.8 (95% CI [13.3-27.7]) months. Three patients had in-field failure, five had out-field failure and two had in-field and out-field failure. WBRT plus SIB led to improved tumor control and clinical outcome in breast cancer patients with brain metastasis.

A comparative study of microsurgery and radiosurgery for acoustic neuroma: Tumor control, hearing preservation, and functional outcomes

A comparative study of microsurgery and radiosurgery for acoustic neuroma: Tumor control, hearing preservation, and functional outcomes

Long-term Outcomes from a Phase 1 Dose Escalation Study Using Stereotactic Body Radiotherapy for Patients with Low- or Intermediate-risk Prostate Cancer

BackgroundUltrahypofractionated stereotactic body radiation therapy (SBRT) has become a standard treatment intervention for localized prostate cancer. ObjectiveTo report final long-term tumor control outcomes and late gastrointestinal (GI) and genitourinary (GU) toxicities from a single-center phase 1 dose escalation study using SBRT for patients with low- or intermediate-risk prostate cancer. Design, setting and participantsBetween 2009 and 2012, 136 patients were enrolled and treated. The initial dose level was 32.5 Gy in five fractions. Doses were then sequentially escalated to 35 Gy, 37.5 Gy, and 40 Gy in five fractions delivered every other day. Outcome measurements and statistical analysisThe primary endpoint was late treatment-related toxicity. Secondary endpoints included prostate-specific antigen (PSA) failure. Results and limitationsThe median follow-up was 10.5 yr for the 32.5-Gy group, 9.9 yr for the 35-Gy group, 8.2 yr for the 37.5-Gy group, and 7.3 yr for the 40-Gy group. The 8-yr cumulative incidence of PSA failure was 26% for 32.5 Gy, 15% for 35 Gy, 3.4% for 37.5 Gy, and 6.6% for 40 Gy. Higher radiation dose (37.5–40 Gy) and favorable intermediate risk (vs unfavorable intermediate risk) were associated with better PSA recurrence rates (p = 0.011 and 0.002, respectively). The 8-yr actuarial probability rates for survival free from late grade ≥2 toxicity were 94% for GI toxicity and 86% for GU toxicity. No grade 4 events were recorded. Higher dose levels were not associated with higher rates of late grade ≥2 GI (p = 0.2) or GU (p > 0.9) toxicity. ConclusionsSBRT doses ranging from 32.5 to 40 Gy were associated with low incidence of moderate or severe toxicities. Higher doses resulted in superior disease control outcomes 8 yr after treatment. Patient summaryWe investigated the association between the radiotherapy dose used and the rate of control of prostate cancer. We found that higher doses resulted in more favorable outcomes without excess toxicity.This trial is registered on ClinicalTrials.gov as NCT00911118.

Intensified NK cell therapy in combination with low-dose chemoradiotherapy against human colorectal cancer.

The therapeutic potential of adoptive natural Killer (NK) cells immunotherapy in combination with chemoradiotherapy, the main treatment modality for colorectal cancer (CRC), has not yet been explored. Here, we aimed to investigate the efficacy of NK cells to potentiate primary tumor control and improve survival outcomes, especially in combination with low-dose chemoradiotherapy. Ex vivo activated NK cells (> 90% purity) from healthy donors were obtained. NK cells were administered intravenously to the CRC-bearing mice and intensified in vivo in combination with low-dose 5-fluorouracil (0.5mg/kg or 1mg/Kg) and irradiated tumors with low doses (2Gy or 4Gy). Real-time NK cell cytotoxicity demonstrated a synergistic killing effect of a combination of low-dose chemoradiotherapy, mainly through NKp30 and NKG2D, showing a decrease in NK cell degranulation after blocking NKG2D and NKp30. In vivo tumor characteristics after combination treatment showed decreased CD112, CD155, MICA, and MICB expression. Under the combination strategy, 70% of the mice had free lung metastasis and 90% without secondary gross tumors, indicating suppressed distant metastasis to lung and axillary regions. This combination therapy resulted in significantly synergistic antitumor activity against primary solid tumors compared to chemoradiotherapy only. Furthermore, the intensified NK cell administration showed significantly better primary tumor control and survival outcomes than the non-intensified NK cell administration in a human colorectal HT-29 model treated with low-dose chemoradiotherapy. Optimized NK cell therapy combined with low-dose chemoradiotherapy can provide effective therapeutic potential for intractable cold human colorectal cancer.

A Prospective Phase II Dose Escalation Study Using IMRT for High Risk N0M0 Prostate Cancer.

Published data supports the use of very high dose intensity modulated radiotherapy (IMRT) in achieving high efficacy and low toxicity for high-risk prostate cancer (HRPCa). This phase II multi-institutional non-randomized prospective dose escalation study using intensity modulated radiotherapy (IMRT) for high risk N0M0 prostate cancer was designed to investigate dose escalation using 1.8 Gy increments from baseline 75.6 Gy up to maximum 81 Gy, once dose volume constraints were adhered to. Inclusion criteria were patients undergoing a radical course of RT for high and very high-risk disease, defined as one or more of the criteria ≥ T3*, ≥ Gleason 8, Prostate specific antigen (PSA) > 20ng/ml. All patients received Androgen Deprivation Therapy (ADT) and none had radiological evidence of distant metastatic disease. The primary objective was to determine if dose escalated IMRT for high risk localized prostate cancer could provide freedom from biochemical relapse (BR; PSA rising > nadir +2ng/mL or initiation of salvage hormone therapy) similar to that reported in the literature. The Kaplan-Meier method was used to estimate survival times. Secondary objectives included OS, Disease Free Survival (DFS), and the incidence and severity of Genito-urinary (GU), Gastro-intestinal (GI) and erectile dysfunction (ED) toxicities (CTCAE v.3). Toxicities and performance status were collected and graded weekly during RT, 2 months after completing RT, 8 months' post RT, and 6 monthly thereafter to year five and annually thereafter to year nine. A total of 230 evaluable patients were enrolled between April 2009 and June 2016. The median follow-up was 7.3 years. The cumulative proportion of patients surviving without BR at 5 years was 91% (95% Confidence Interval (CI): 86% to 94%). Overall survival at 5 and 7 years was 92% (88% to 95%) and 89% (83% to 92%) respectively, while the cumulative proportion of patients free from disease was 89% (84% to 93%) at 5 years and 81% (75% to 86%) at 7 years. The incidence of acute G2 and G3 toxicities were; GU; 57.8% G2, 12.6% G3, GI; 15.2% G2, 0.4% G3, ED; 30.0% G2 and 61.7% G3. The incidence of late G2, G3 and G4 toxicities were; GU; 40.9% G2, 8.7% G3, GI; 36.5% G2, 2.2% G3, 0.4% G4, ED; 11.7% G2 and 86.1% G3. The percentage of patients receiving each dose level was; 3.5% received 75.6Gy in 42 fractions, 2.2% received 77.4Gy in 43 fractions, 93% received 81Gy in 45 fractions. The findings indicate that high-dose IMRT is well tolerated and is associated with excellent long-term tumor-control outcomes in patients with localized high and very high-risk prostate cancer, with 91% of patients surviving at 5 years without biochemical relapse. The rates of long term G3 GU and GI toxicity were low at 8.7% and 0.4% respectively.

Surgically Targeted Radiation Therapy (STaRT) for Brain Metastases: Initial Experience from a Prospective Multi-Institutional Registry

Resection and intraoperative brachytherapy for patients with large, operable brain metastasis allows for both relief of mass effect and the delivery of radiotherapy (RT) to the resection cavity with a favorable dosimetric profile. The objective of this study was to analyze early patterns-of-care and treatment-related toxicity outcomes for brain metastasis patients treated with surgically targeted radiation therapy (STaRT) using a novel brachytherapy carrier. Patients with brain metastasis, de novo and recurrent disease, who enrolled onto a prospective multi-institutional observational study (NCT04427384) were the subject of this analysis. Patients underwent resection and immediate implantation of bioresorbable, conformable, 20 mm x 20 mm x 4 mm collagen tile brachytherapy device(s) containing four uniform-intensity Cesium-131 sources. Toxicities were categorized using the CTCAE v5.0 adverse event (AE) criteria. From 10/2020 to 01/2023, 13 participating sites enrolled and treated 48 patients with 51 metastases (13 with de novo and 35 patients with recurrent brain metastases), and 3 patients had 2 lesions implanted at the same procedure. Median age was 61 years (range: 28-80), 52% were female, and the most common primary types were lung (56%) and breast (13%). The median maximum pre-operative dimension was 3.4 cm (range: 1.7-5.7) and median pre-operative tumor volume 13.7cm3 (range: 1.7-132). 64% had received prior RT with a median time from last RT to STaRT of 14.6 months range: 3.5-57.3). Median KPS at screening was 80 (range: 50-100), and remained stable at post op visit (80, range: 50-100), and at 3-months following treatment (80, range 50-100), respectively (p>0.05). The median time for implantation was 3 minutes (range: 0.4-30). At a median follow-up of 4 months (range: <1-18), no patient experienced a radiation-attributed AE, and only 1 attributable Gr >3 AE was noted (Gr 5 intracerebral hemorrhage deemed probably related to surgery and unrelated to the implanted device). Early results from this prospective multi-center trial demonstrate the feasibility and safety of STaRT. The lack of radiation-related AE, even with short follow-up, is intriguing given the relatively large lesion size and proportion of patients treated for recurrent, previously irradiated disease. Additional follow-up will provide data on tumor control outcomes and radiation necrosis rates using this novel technique.

Differential Response to Radiation Fractionation in Head and Neck Cancer Patient-Derived Xenografts

Despite optimal management with conventionally fractionated radiotherapy, head and neck cancer (HNC) mortality is driven by locoregional failure. With the increasing development of hypofractionated regimens in other malignancies, we sought to investigate the sensitivity of patient HNC to radiation fractionation using murine patient-derived xenografts (PDXs). We developed PDXs from three HNC patients who underwent primary surgical resection and enrolled on our IRB-approved (PRO00040992) prospective HNC tumor bank by implanting freshly resected tumors subcutaneously in the flank of NSG-SGM3 mice. PDXs from each patient were randomized to receive no radiation, 2 Gy x 5 fractions delivered daily (conventional arm) or 10 Gy in a single fraction (hypofractionation arm). Tumor volume was measured until 15 days post-RT, when mice were sacrificed. Bulk RNA sequencing analysis was performed on PDX tumors after intervention. Three PDX tumors from three unique patients (P006, P010 and P016) were successfully developed and irradiated per protocol. Unique responses to radiation were seen with each tumor: P010 showed equal sensitivity to both the conventional and hypofractionated regimens; P006 showed intermediate sensitivity to the conventional regimen with high sensitivity to hypofractionation, and P016 was resistant to conventional fractionation but showed sensitivity to hypofractionation. Concurrent with the patient-specific PDX response to fractionation, principal component analysis demonstrated that each patient PDX had a unique signature of differentially expressed genes in response to the conventional and hypofractionated regimens. HNC PDXs show differential tumor and genomic response to radiation fractionation regimens. A precision approach to radiation fractionation for HNC may improve tumor control outcomes in HNCs.

Hypofractionated Radiotherapy for Prostate Cancer (HRT20) Trial: Results

Radiotherapy is a definitive standard treatment for men with localized prostate cancer. Improvements in technology allow higher doses of radiation delivered to the prostate in less days, with lower doses to surrounding healthy tissues trying to reduce side effects. Several studies demonstrated that hypofractionated radiotherapy of 60 Gy is non-inferior to conventional radiotherapy fractionation. To report the first results in toxicity and biochemical relapse free survival of HRT20 trial after 5 years of recruitment. The HRT20 trial is registered (NCT03851926). A prospective observational study enrolled 298 men with localized prostate cancer (pT1b-T3aN0M0) started in October 2016. Median age was 75 (53-91). Median PSA was 14.5ng/ml. Using NCCN classification: 12,6% were low risk, 50.5% were intermediate and 36.9 % were high risk patients. The median duration of the treatment was 30 days (23-41) The clinical target volume (CTV) consisted of the prostate and seminal vesicles when affected. The CTV-planning target volume (PTV) margin was 0.8 cm. The primary end point evaluated assessed by CTCAE 4.0 was related later adverse events and the second end point was biochemical relapse free survival by Phoenix definition. WMAT plans calculations were carried out using the Monaco TPS version 5.10 based on a single arc arrangement. Univariate and multivariate logistic analyses were carried out. After median follow up of 56 months. The 5-year incidence rates of grade 2 and 3 late gastrointestinal toxicities were 6.3% and 3.1%, respectively, and those of grade 2 and 3 late genitourinary toxicities were 7.9% and 1%, respectively. PTV volume was found to be correlated with late rectal bleeding (p = 0.02). Also, urinary tract obstruction was correlated with PTV volume. The proportion of patients who were biochemical failure free at 5 years was 88·3% (95% CI 86·0-90·2) Multivariate analysis indicated that risk stage (p = 0.03) and number of positive needles biopsy cores (p = 0.02) were prognostic factor for biochemical relapse-free survival rates. The findings of this study indicate that hypofractionated is well tolerated and it is associated with good 5-years tumor-control outcomes in patients with localized prostate cancer. Long-term follow-up continues.

P18.03.A HYPOFRACTIONATION WITH OPTIMIZED STEREOTACTIC RADIOSURGERY PLANNING FOR SKULL BASE PERIOPTIC MENINGIOMAS

Abstract BACKGROUND Skull base perioptic meningiomas are challenging for stereotactic radiosurgery (SRS). The therapeutic window between tumor control and normal tissue complication is extremely narrow in these tumors, especially of large volume and/or in close proximity to the optic apparatus (OA). To minimize the risk of radiation toxicity, we optimized our SRS plans in terms of both steeper dose fall-off and dose-volume constraints for OA and delivered hypofractionation treatment. MATERIAL AND METHODS Thirty-one patients had been treated with hypofractionated SRS using the CyberKnife for perioptic meningiomas &amp;gt; 10 cm3 in volume (median 18.9 cm3). Tumor locations were cavernous sinus (n=7), petroclival (n=6), and tentorial edge (n=6). Optimization in SRS planning was carried in two aspects: 1) for steeper dose fall-off, multiple virtual shells outside the target were introduced and appropriate dose limits (formulated from our own Gamma Knife data) were applied; and 2) to minimize the risk of optic neuropathy, dose-volume constraints for OA (from AAPM TG101) were applied. SRS was delivered in five daily fractions with a median cumulative dose 27.8 Gy. RESULTS With a median follow-up of 33 months, tumor control was achieved in 28 of 31 patients (90.3%). Treatment response on MRI included partial response (volume decrease &amp;gt; 20%) in 17 patients, stable in 11, and progression (volume increase &amp;gt; 20%) in 3. Neurological symptoms improved in 10 patients, unchanged in 20, and worsened in 1. CONCLUSION Our current results show a promising role of hypofractionated SRS with optimization in steeper dose fall-off and dose-volume constraints for OA for large-sized skull base perioptic megningiomas in terms of both tumor control and neurological outcomes.