Local Tumor Control Research Articles

Complex Treatment of A Rare Non-Germinomatous Germ Cell Optic-Chiasmal Brain Tumor In An Adolescent Child-A Clinical Case With Literature Review

Non-germ cell tumours (NGCTs) are rare intracranial neoplasms occurring in adolescents and young adults. A multidisciplinary team including a neurosurgeon, oncologist, radiologist, pathohistologist, ophthalmologist, pediatric oncohematologist, neurologist and endocrinologist is required for diagnosis and treatment. We present a rarely diagnosed optic-chiasmal non-germinomatous germ cell tumour (NGGCT) in a 16-year-old boy, accompanied by pituitary insufficiency (diabetes insipidus and central hypothyroidism) and severely impaired vision bilaterally. The immunohistochemistry (IHC) of the tumor biopsy, as well as the level of tumor markers (human chorionic gonadotropin and alpha-fetoprotein) in the serum and cerebrospinal fluid are significant factors for determining the diagnosis-cranial GCT or cranial NGCT. Because the tumor was inoperable, we performed 3 courses of neoadjuvant chemotherapy followed by definitive radiotherapy to a total tumor dose of 55 Gy. In such rare childhood brain tumors, complex treatment achieves long-term local tumor control, requiring long-term monitoring by an ophthalmologist and endocrinologist.

Ablation of Kidney Tumors in Patients with Substantial Kidney Impairment: Current Status.

To review the current status of kidney tumor ablation in patients with substantial kidney impairment. Few reports of kidney tumor ablation in such patients have recently been published. The reported prevalence of patients with stage 4 or 5 chronic kidney disease (CKD) among patients undergoing ablation is 2.0%-10%. In patients with stage 4 or 5 CKD, local tumor control rates were 88%-100%. The effect of ablation on CKD stage is unclear, and the observed deteriorations in kidney function are consistent with both the effect of cryoablation and the natural course of advanced CKD. According to guidelines, active surveillance may be selected. The goals of treatment are complete tumor removal and maintenance of kidney function, both of which can be met by ablation. Given the limited treatment options, ablation may play a pivotal role in the management of patients with advanced CKD.

Abstract CT080: A phase I study of CPI-613 (devimistat) in combination with chemoradiation in patients with pancreatic ductal adenocarcinoma

Abstract Background: Local tumor progression is a cause of significant mortality and morbidity in patients (pts) with inoperable pancreatic ductal adenocarcinoma (PDAC). Effective approaches to achieve durable local control are urgently needed. Metabolic reprogramming and enhanced mitochondrial function are known contributors to chemo- and radio-resistance in PDAC. CPI-613, a lipoic acid analog that selectively inhibits components of the Krebs cycle in tumors, showed promising preclinical synergy in combination with gemcitabine and radiation (gem-RT). We initiated a phase I study (NCT05325281) to determine the maximum tolerated dose (MTD) of CPI-613 when used with gem-RT. Here, we present the results from the first cohort of this study. Methods: Adult pts with inoperable PDAC that, by institutional multidisciplinary review, were considered to benefit from definitive local control of the primary tumor were eligible for the study. CPI-613 was administered once weekly by intravenous infusion over ~ 2 hours at a starting dose of 500 mg/m2 and dose-escalated using a Bayesian optimal interval design. Gemcitabine was given once weekly at 400 mg/m2 and RT at 45-54 Gray (Gy) in 25-30 fractions. Results: By Jan 7, 2024, six pts were enrolled, and five completed the treatment and dose-limiting toxicity (DLT) period. Table 1 describes the characteristics of these five pts. As CPI-613 was not associated with any additional toxicities, specifically cytopenia(s), after the first two pts, the study protocol was amended to allow CPI-613 to be administered on weeks gemcitabine was held for cytopenia(s). The study, therefore, enrolled five pts in the first cohort. All pts received ≥ 16 weeks of systemic chemotherapy with at least stable disease per imaging prior to enrollment. None of the pts experienced DLTs. All treatment-related toxicities were expected from gem-RT, unrelated to CPI-613, and manageable. The trial is currently enrolling pts in the second cohort (CPI-613 dose of 1000 mg/m2). Conclusions: CPI-613 combined with gem-RT was safe and well tolerated at a dose of 500 mg/m2. Recruitment to the study is ongoing to determine the MTD of CPI-613 in combination with gem-RT. Table 1. Characteristic of Patients Sex Race Age ECOG Stage Prior chemotherapy Chemotherapy duration (weeks) M W 67 1 LA FFX 16 M W 64 1 LA GnP 35 M W 73 1 BR* GnP 16 M B 71 1 LA GnP 27 M W 80 1 Oligometastatic** GnP 18 * Medically inoperable ** Two lung metastases treated with stereotactic body radiation therapy (SBRT); BR: Borderline resectable; B: Black; FFX: FOLFIRINOX; GnP: Gemcitabine/Nab-paclitaxel; LA: Locally advanced. M: Male; W: White Citation Format: Mandana Kamgar, Husain Yar Khan, Amro Aboukameel, Sahar F. Bannoura, Brian Y. Chung, Aniko Szabo, Yiwei Li, Mohammed Najeeb Al Hallak, Philip A. Philip, Ben George, Kathleen K. Christians, Douglas B. Evans, Susan Tsai, Beth Erickson, John M. Goldberg, Asfar S. Azmi, William A. Hall. A phase I study of CPI-613 (devimistat) in combination with chemoradiation in patients with pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT080.

Abstract LB084: Radiation and anti-PD-L1 synergize by stimulating a stem-like T cell population in the tumor-draining lymph node

Abstract Radiotherapy (RT) and anti-PD-L1 synergize to enhance local and distant (abscopal) tumor control. However, clinical results in humans have been variable. With the goal of improving clinical outcomes, we investigated the underlying synergistic mechanism focusing on a TCF-1+ PD-1+ CD8+ stem-like T cell subset in the tumor-draining lymph node (TdLN). We found that RT + anti-PD-L1 induces a novel differentiation program in the TdLN stem-like population which leads to their expansion and differentiation into effector cells within the tumor. We also found that optimal synergy between RT + anti-PD-L1 is dependent on the TdLN stem-like T cell population as either blockade of TdLN egress or specific stem-like T cell depletion reduced tumor control. Together, these data demonstrate a multistep stimulation of stem-like T cells following combination therapy which is initiated in the TdLN and completed in the tumor. Citation Format: Yang Shen, Erin Connolly, Meili Aiello, Chengjing Zhou, Haorui Song, Tarralyn Clark, Patan Tippitak, Gregory B. Lesinski, Chrystal Paulos, Nikki Schmitt, Zachary S. Buchwald. Radiation and anti-PD-L1 synergize by stimulating a stem-like T cell population in the tumor-draining lymph node [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB084.

Tumor- and Radiation-Related Complications after Ruthenium-106 Brachytherapy in Small to Medium Uveal Melanomas (Part 1).

The purpose of this study was to analyze tumor-related complications after ruthenium-106 brachytherapy in patients with uveal melanoma, with respect to local tumor control, insufficient radiation response, enucleation, and metastasis rate. This retrospective study included 608 patients treated consecutively with ruthenium-106 brachytherapy between January 2008 and December 2010 at the Department of Ophthalmology, University Hospital Essen. The occurrence of radiation-induced results was analyzed by estimating the risk by applying the Kaplan-Meier method, i.e., the "time to event" analysis. The Cox model test was used for the univariate and multivariate risk factor analyses. The median follow-up was 51 months after primary treatment. Tumor recurrence was found in 21 patients (3.5%) and repeated treatment due to insufficient effect after the initial ruthenium-106 brachytherapy was performed in 40 patients (6.6%). The 5-year cumulative risk of recurrence was 4.0% and that of insufficient effect was 7.3%. Thirteen patients (2.1%) underwent a secondary enucleation; 8 because of a local recurrence and 5 because of severe post-brachytherapy complications. The cumulative enucleation risk was 2.3% after 5 years and 2.9% after 10 years, corresponding to eye preservation of 97.7 and 97.1%, respectively. In forty-two patients (7.2%), metastatic disease was diagnosed during the follow-up. The metastatic rate as calculated by the Kaplan-Meier method was 9.0, and 13.1% at 5 and 10 years, respectively. Our study demonstrated that ruthenium-106 brachytherapy is an excellent treatment option for achieving local tumor control and eye preservation in well-selected patients. The metastatic rate is in agreement with that of previous studies analyzing small to medium size uveal melanomas.

1134 A Call to Revise the Thirty-year-old SRS Dose Guidelines for Brain Metastases

INTRODUCTION: Stereotactic Radiosurgery (SRS) currently is the most widely used neurosurgical strategy for treatment of brain metastases. Many centers still rely on 30-year-old dose volume guidelines derived from RTOG 90-05. METHODS: Between 2014 and 2020 330 NSCLC patients (median age = 65 years) with 2910 brain metastases underwent Gamma knife SRS. The number of tumors treated per patient ranged from 1-56 and the total tumor cumulative volume ranged from .05 to 33.09 cc (median = 3.17). The median prescribed tumor margin dose was 18 Gy. RESULTS: Median overall survival after radiosurgery was 15.5 months. Radiological tumor progression was noted 66 out of 2910 tumors (2.27%) in 51 out of 330 patients (15.45%). Tumors were divided into 4 categories based on tumor volumes (<1.5 cc, 1.5-<5 cc, 5-<10 cc, and = 10cc). The effect of margin dose, and % tumor covered in 18 Gy, 20 Gy, and 24 Gy on local tumor control was analyzed for all 4 categories. In tumors with volumes >1.5 cc local tumor control was significantly better (P < 0.05) when =65% of the tumor volume received at least 24 Gy. No relationship was found between tumor control and 75, 90, and 100 % volumes receiving 18 or 20 Gy. CONCLUSIONS: In this study neither conformality of dose delivery nor tumor margin doses were the most important predictors of local tumor control as long as =65% of the tumor volume received at least 24 Gy. This finding can serve as a prescriptive guideline that allows margin doses below the RTOG guidelines, reduces reliance on strict conformality, and improves tumor control.

199 Gamma Knife Radiosurgery to Treat Neurofibromatosis Type 2-Associated Meningiomas: A 35 Year Experience and Paradigm for Future Treatment

INTRODUCTION: Management of neurofibromatosis type 2 (NF2)-associated meningiomas remains a case-by-case basis, and treatment options vary. METHODS: Forty-nine patients (22 male, 44.90%) with 213 NF2-associated meningiomas treated with SRS between 1987 and 2022 were retrospectively reviewed. The median age at SRS was 56 (range: 20-79) years. Twenty-nine (59.18%) patients had pre-SRS surgical resection, and 7 (14.29%) had prior radiotherapy. The median number of meningiomas per patient was 2 (range: 1-17), the median margin dose was 13 (range: 9-16) Gy, and the median cumulative tumor volume per patient was 8.30 (range: 0.10-74.26) cm3. RESULTS: Nine patients (18.37%) had local tumor progression. The 1- and 5-year local tumor control rates were 100% and 90.54%, respectively. Tumor volume < 8.30 cm3 was associated with better local tumor control (p = 0.02, HR: 1.06, 95% CI: 1.01-1.12) on multivariate analysis. Twenty-five patients (51.02%) had detection of new growing tumors (DNGT). The 1- and 5-year DNGT rates were 78.05% and 47.38%, respectively. On multivariate analysis, >2 meningiomas at SRS presentation per patient (p = 0.01, HR: 1.09, 95% CI: 1.02-1.17) was significantly associated with DNGT. Neurological symptoms improved in 20 patients (40.82%), remained stable in 28 patients (57.14%), and worsened in 1 (2.04%) patient at a median follow-up time of 81 (range: 6–267) months after SRS. Seventeen (34.69%) patients were deceased at last follow-up, and 4 patients expired due to intracranial disease progression. Two (4.08%) patients developed transient adverse radiation effects; no patients developed secondary malignancies. CONCLUSIONS: Single-session SRS can effectively be used to control tumor progression and improve neurological symptoms in NF2-associated meningioma patients while limiting adverse radiation effects.

499 Silent Corticotroph Staining Pituitary Neuroendocrine Tumors: Prognostic Significance in Radiosurgery

INTRODUCTION: There is conflicting evidence on the significance of adrenocorticotrophic hormone (ACTH) staining in the prognosis of nonfunctioning pituitary neuroendocrine tumors (NFpitNETs). METHODS: This retrospective, multicenter study included patients managed with SRS for NFpitNET residuals. The patients were divided into two cohorts: 1) silent corticotroph (SC) for NFpitNETs with positive ACTH immunostaining and 2) non-SC NFpitNETs. Rates of local tumor control, as well as the incidence of post-treatment pituitary and neurological dysfunction were documented. Factors associated with radiological and clinical outcomes were also analyzed. RESULTS: The cohort included 535 patients from fourteen centers with 84 (15.7%) patients harboring silent corticotroph NFpitNETs (SCs). At last follow-up, local tumor progression occurred in 11.9% of patients in the SC compared to 8.1% of patients in the non-SC cohort (p = 0.27). No statistically significant difference was noted in new-onset hypopituitarism rates (10.7% vs 15.4%, p = 0.25) or visual deficits (3.6% vs 1.1%, p = 0.088) between the two cohorts at last follow-up. When controlling for residual tumor volume, maximum dose, and patient age and gender, positive ACTH immunostaining did not have a significant correlation with local tumor progression (HR = 1.69, 95% CI = 0.8 - 3.61, p = 0.17). CONCLUSIONS: In contemporary radiosurgical practice with a single fraction dose of 8-25 Gy (median 15 Gy), ACTH immunostaining in NFpitNETs did not appear to confer a significantly reduced rate of local tumor control after SRS.

Radiation toxicity grading after chemoradiotherapy of canine urinary tract carcinomas: Comparing VRTOG to VRTOG_v2.0.

Radiation toxicities may be underestimated after treatment of transitional cell carcinoma in dogs' lower urinary tract. Assessing acute and late toxicities and differentiating them from progressive disease (PD) impacts further therapeutic approach. We retrospectively assessed dogs treated with definitive-intent chemoradiotherapy (12 × 3.8 Gy, various first-line chemotherapeutics). Local tumour control, radiation toxicities and survival were evaluated. We classified radiation toxicities according to the previously published radiation toxicity scheme "VRTOG" as well as the updated version, "VRTOG_v2.0". Fourteen dogs with transitional cell carcinoma of bladder ± urethra (n = 8), +prostate (n = 3) or solely urethra (n = 3), were included. Median follow-up was 298 days (range 185-1798 days), median overall survival 305 days (95%CI = 209;402) and 28.6% deaths were tumour-progression-related. Acute radiation toxicity was mild and self-limiting with both classification systems: In VRTOG, 5 dogs showed grade 1, and 1 dog grade 2 toxicity. In VRTOG_v2.0, 2 dogs showed grade 1, 3 dogs grade 2, and 3 dogs grade 3 toxicity. Late toxicity was noted in 14.2% of dogs (2/14) with the VRTOG, both with grade 3 toxicity. With VRTOG_v2.0, a larger proportion of 42.9% of dogs (6/14) showed late toxicities: Four dogs grade 3 (persistent incontinence), 2 dogs grade 5 (urethral obstructions without PD resulting in euthanasia). At time of death, 5 dogs underwent further workup and only 3 were confirmed to have PD. With the updated VRTOG_v2.0 classification system, more dogs with probable late toxicity are registered, but it is ultimately difficult to distinguish these from disease progression as restaging remains to be the most robust determinant.

Complications and local recurrence of chondrosarcoma and chordoma treated by total tumor resection in thoracic and lumbar spine

BackgroundEn bloc resection of spinal tumors is challenging and associated with a high incidence of complications; however, it offers the potential to reduce the risk of recurrence when a wide margin is achieved. This research aims to investigate the safety and efficacy of en bloc resection in treating thoracic and lumbar chondrosarcoma/chordoma.MethodsData from patients diagnosed with chondrosarcoma and chordoma in the thoracic or lumbar region, who underwent total en bloc or piecemeal resection at our institution over a 7-year period, were collected and regularly followed up. The study analyzed overall perioperative complications and compared differences in complications and local tumor recurrence between the two surgical methods.ResultsSeventeen patients were included, comprising 12 with chondrosarcoma and 5 with chordoma. Among them, 5 cases underwent intralesional piecemeal resection, while the remaining 12 underwent planned en bloc resection. The average surgical time was 684 min (sd = 287), and the mean estimated blood loss was 2300 ml (sd = 1599). Thirty-five complications were recorded, with an average of 2.06 perioperative complications per patient. 82% of patients (14/17) experienced at least one perioperative complication, and major complications occurred in 64.7% (11/17). Five patients had local recurrence during the follow-up, with a mean recurrence time of 16.2 months (sd = 7.2) and a median recurrence time of 20 months (IQR = 12.5). Hospital stays, operation time, blood loss, and complication rates did not significantly differ between the two surgical methods. The local recurrence rate after en bloc resection was lower than piecemeal resection, although not statistically significant (P = 0.067).ConclusionsThe complication rates between the two surgical procedures were similar. Considering safety and local tumor control, en bloc resection is recommended as the primary choice for patients with chondrosarcoma/chordoma in the thoracic and lumbar regions who are eligible for this treatment.

Concurrent Atezolizumab Plus Bevacizumab and High-Dose External Beam Radiotherapy for Highly Advanced Hepatocellular Carcinoma.

Atezolizumab plus bevacizumab (atezo-bev) has been recommended for advanced hepatocellular carcinoma (HCC). High-dose external beam radiotherapy (RT) is recognized for its excellent local tumor control. The efficacy and safety of concurrent atezo-bev with RT for highly advanced HCC has been minimally explored. In this preliminary retrospective study, we assessed patients with highly advanced HCC, characterized by Vp4 portal vein thrombosis or tumors exceeding 50% of liver volume, who received concurrent atezo-bev and RT (group A). Group A included 13 patients who received proton radiation at a dose of 72.6 GyE in 22 fractions, and one patient who received photon radiation at a dose of 54 Gy in 18 fractions. This group was compared with 34 similar patients treated atezo-bev alone as a control (group B). The primary objectives were to evaluate the objective response rate (ORR), overall survival (OS), and safety. Baseline characteristics were similar between groups, except for a higher incidence of Vp4 portal vein thrombosis in group A (78.6% vs. 21.4%, P = .05). Group A achieved a higher ORR (50.0% vs. 11.8%, P < .01) and a longer OS (not reached vs. 5.5 months, P = .01) after a median follow-up of 5.2 months. Multivariate analysis indicated that concurrent RT independently favored longer OS (hazard ratio: 0.18; 95% CI, 0.05-0.63, P < .01). Group A did not increase any grade adverse events (78.6% vs. 58.8%, P = .19) or severe adverse events of grade ≥ 3 (14.3% vs. 14.7%, P = .97) compared to group B. The concurrent high-dose external beam radiotherapy appears to safely enhance the effectiveness of atezolizumab plus bevacizumab for highly advanced patients with HCC. Further studies are warranted to confirm these findings.

Histology-driven hypofractionated radiation therapy schemes for early-stage lung adenocarcinoma and squamous cell carcinoma

Background and PurposeHistology was found to be an important prognostic factor for local tumor control probability (TCP) after stereotactic body radiotherapy (SBRT) of early-stage non-small-cell lung cancer (NSCLC). A histology-driven SBRT approach has not been explored in routine clinical practice and histology-dependent fractionation schemes remain unknown. Here, we analyzed pooled histologic TCP data as a function of biologically effective dose (BED) to determine histology-driven fractionation schemes for SBRT and hypofractionated radiotherapy of two predominant early-stage NSCLC histologic subtypes adenocarcinoma (ADC) and squamous cell carcinoma (SCC). Material and MethodsThe least-χ2 method was used to fit the collected histologic TCP data of 8510 early-stage NSCLC patients to determine parameters for a well-developed radiobiological model per the Hypofractionated Treatment Effects in the Clinic (HyTEC) initiative. ResultsA fit to the histologic TCP data yielded independent radiobiological parameter sets for radiotherapy of early-stage lung ADC and SCC. TCP increases steeply with BED and reaches an asymptotic maximal plateau, allowing us to determine model-independent optimal fractionation schemes of least doses in 1–30 fractions to achieve maximal tumor control for early-stage lung ADC and SCC, e.g., 30, 44, 48, and 51 Gy for ADC, and 32, 48, 54, and 58 Gy for SCC in 1, 3, 4, and 5 fractions, respectively. ConclusionWe presented the first determination of histology-dependent radiobiological parameters and model-independent histology-driven optimal SBRT and hypofractionated radiation therapy schemes for early-stage lung ADC and SCC. SCC requires substantially higher radiation doses to maximize tumor control than ADC, plausibly attributed to tumor genetic diversity and microenvironment. The determined optimal SBRT schemes agree well with clinical practice for early-stage lung ADC. These proposed optimal fractionation schemes provide first insights for histology-based personalized radiotherapy of two predominant early-stage NSCLC subtypes ADC and SCC, which require further validation with large-scale histologic TCP data.

Current perspectives on radiotherapy in hepatocellular carcinoma management: a comprehensive review.

This review examines the transformative role of external beam radiotherapy (EBRT) in managing hepatocellular carcinoma (HCC), spotlighting the progression from traditional EBRT techniques to advanced modalities like intensity-modulated radiotherapy (RT), stereotactic body RT (SBRT), and innovative particle therapy, including proton beam therapy and carbon ion RT. These advancements have significantly improved the precision and efficacy of RT, marking a paradigm shift in the multimodal management of HCC, particularly in addressing complex cases and enhancing local tumor control. The review underscores the synergistic potential of integrating RT with other treatments like transarterial chemoembolization, systemic therapies such as sorafenib, and emerging immunotherapies, illustrating enhanced survival and disease control outcomes. The efficacy of RT is addressed for challenging conditions, including advanced HCC with macrovascular invasion, and RT modalities, like SBRT, are compared against traditional treatments like radiofrequency ablation for early-stage HCC. Additionally, the review accentuates the encouraging outcomes of particle therapy in enhancing local control and survival rates, minimizing treatment-related toxicity, and advocating for continued research and clinical trials. In conclusion, the integration of RT into multimodal HCC treatment strategies, coupled with the emergence of particle therapy, is crucial for advancing oncologic management, emphasizing the need for relentless innovation and personalized treatment approaches.

Abstract 7396: Development of deep neural networks that guide more individualized radiotherapy to the lung

Abstract Introduction: Radiotherapy is dependent on an expert-based model that impedes implementation of many potentially useful applications that could aid decision makers. This model is a barrier to a learning healthcare system due to noise introduced by decision-maker variation. Surmounting this barrier will require compelling clinical outcome data and highly useful and accurate information systems. We sought to develop new augmented-intelligence capabilities to better predict both high-dose lung irradiation treatment efficacy (i.e., local tumor control) and toxicity (i.e., radiation-induced pneumonitis). Methods: We curated one of the largest datasets of lung stereotactic body radiotherapy (SBRT) datasets globally (~1200 cases). We input pre-therapy lung computed tomography (CT) images using a bounding box approach that captures the gross tumor volume and adjacent normal lung into a multi-task deep neural network to generate an image fingerprint that predicts local failures after treatment. Separately, we input axial slices from CT scans of the lung into convolutional neural network (CNN) and trained using an outcome per slice method. We then aggregated intra-patient slices into a recurrent neural network (RNN) to estimate individual patient risk for pneumonitis. We validated our findings with the independent study cohort. Risk scores for local failure and pneumonitis were combined with clinical variables to assess the relative contribution of the deep learning-derived image risk scores. Results: A total of 1045 patients met our eligibility criteria. Radiation treatments in patients with high local failure risk scores failed at a significantly higher rate than in patients with low scores; 3-year cumulative incidence of local failure in the internal study cohort was 20·3% (16·0-24·9) in patients with high scores and 5·7% (95% CI 3·5-8·8) in patients with low scores (hazard ratio [HR]=3·64 [95% CI 2·19-6·05], p&amp;lt;0·0001). Models that included the local failure risk score and clinical variables predicted treatment failures with a concordance index (C-index) of 0·72 (95% CI 0·67-0·77), a significant improvement compared with classical radiomics (p&amp;lt;0·0001) or clinical variables (p&amp;lt;0·0001) alone. Radiation pneumonitis risk scores were highly predictive of toxicity, with an accuracy and CI of 0.78 (95% CI 0.72-0.85). A model that includes dosimetry variates (V20), improved the CI to 0.85 (95% CI 0.80-0.90). Conclusions: The image-based deep learning frameworks developed herein represent the first opportunity to use medical images to individualize radiotherapy dose and toxicity predictions. Our results signify a new roadmap for deep learning-guided predictions and treatment guidance in the image-replete and highly standardized discipline of radiation oncology. A phase 2 study assessing machine-derived dose predictions is currently enrolling patients. Citation Format: Mohamed Abazeed. Development of deep neural networks that guide more individualized radiotherapy to the lung [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7396.

Abstract 5519: Enlarged metastasis-free tumor-draining lymph node is a marker of tumor invasion in local tissues with an active NK cell-mediated immunity

Abstract Background: Colorectal cancer (CRC) is the third most common cancer worldwide, accounting for about 10% of all new cancer cases. The tumor-draining lymph node (TDLN) is a key site for the development of anti-tumor immunity that has been reported to be involved in both CD8+ T and NK cells. As a major role of innate immunity, NK cells can produce IFN-γ, perforin and granzyme to eliminate tumor cells in the early stages of cancer development. This study aimed to investigate the difference of clinicopathological and immunological profiles in local tissues between CRC patients with enlarged and non-enlarged metastasis-free TDLNs. Methods: The patient cohort was obtained from the NEPDC cohort (No. 2015CB554000). A total of 45 patients with pathologically confirmed stage I-II colorectal cancer were included in this study. Based on the MRI, these patients were divided into enlarged and non-enlarged TDLN groups (lymph nodes &amp;gt;/= 5mm and lymph nodes &amp;lt; 5mm). We collected the tumor tissue and tumor-adjacent normal tissue that was 2 cm away from the tumor lesion. The genomic DNA of the tumor and tumor-adjacent normal tissues was treated with bisulfite and analyzed with the EPIC methylation array. The MeTMEC algorithm based on the methylation profile estimated subsequent cell abundance in these patient tissues. Results: The study sample was comprised of 22 enlarged TDLN and 23 non-enlarged TDLN patients. There were 4 T1-T2 and 18 T3-T4 patients in the enlarged TDLN group, with 12 T1-T2 and 11 T3-T4 patients in the non-enlarged TDLN group. The proportion of T3-T4 patients in the enlarged TDLN group was higher than that in the non-enlarged TDLN group (p=0.017, Chi-squared test), suggesting an advanced invasion in the local tissue of patients with enlarged TDLN. Then, the abundance of monocytes, dendritic cells, macrophages, neutrophils, eosinophils, Treg cells, naive T cells, memory T cells, CD8+ T cells, NK cells, and B cells in the tumor and tumor-adjacent normal tissues were inferred with the MeTMEC algorithm by using DNA methylation profile. In the T1-T2 subset, we found that the infiltration of NK cells in the tumor-adjacent normal tissues was significantly more abundant in the enlarged TDLN group compared with the non-enlarged TDLN group (p=0.021, t-test), suggesting an active immune response of NK cells for potential local tumor control. No significant difference in other immune cells was observed between the two groups. Conclusion: Enlarged TDLN indicates an advanced invasion of tumors in local tissues with an active NK cell-mediated immunity. Our findings suggest that enlarged metastasis-free TDLN might be a promising marker for NK cell-based cancer immunotherapy. Key words: Colorectal Cancer, Lymph Nodes, Natural Killer Cells Citation Format: Zixiao Wan, Huichuan Yu. Enlarged metastasis-free tumor-draining lymph node is a marker of tumor invasion in local tissues with an active NK cell-mediated immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5519.

The Added Value of Transcatheter CT Hepatic Angiography (CTHA) Image Guidance in Percutaneous Thermal Liver Ablation: An Experts' Opinion Pictorial Essay.

With the rapidly evolving field of image-guided tumor ablation, there is an increasing demand and need for tools to optimize treatment success. Known factors affecting the success of (non-)thermal liver ablation procedures are the ability to optimize tumor and surrounding critical structure visualization, ablation applicator targeting, and ablation zone confirmation. A recent study showed superior local tumor progression-free survival and local control outcomes when using transcatheter computed tomography hepatic angiography (CTHA) guidance in percutaneous liver ablation procedures. This pictorial review provides eight clinical cases from three institutions, MD Anderson (Houston, TX, USA), Gustave Roussy (Paris, France), and Amsterdam UMC (Amsterdam, The Netherlands), with the intent to demonstrate the added value of real-time CTHA guided tumor ablation for primary liver tumors and liver-only metastatic disease. The clinical illustrations highlight the ability to improve the detectability of the initial target liver tumor(s) and identify surrounding critical vascular structures, detect 'vanished' and/or additional tumors intraprocedurally, differentiate local tumor progression from non-enhancing scar tissue, and promptly detect and respond to iatrogenic hemorrhagic events. Although at the cost of adding a minor but safe intervention, CTHA-guided liver tumor ablation minimizes complications of the actual ablation procedure, reduces the number of repeat ablations, and improves the oncological outcome of patients with liver malignancies. Therefore, we recommend adopting CTHA as a potential quality-improving guiding method within the (inter)national standards of practice.

Percutaneous Image-Guided Cryoablation of Endophytic Renal Cell Carcinoma

PurposeEndophytic renal cancer treatment is a challenge. Due to difficulties in endophytic tumor visualization during surgical extirpation, image-guided percutaneous cryoablation (PCA) is an attractive alternative. The minimally invasive nature of PCA makes it favorable for comorbid patients as well as patients in which surgery is contraindicated. Oncological outcomes and complications after PCA of endophytic biopsy-proven renal cell carcinoma (RCC) were reviewed in this study.Materials and MethodsPatients were included after a multidisciplinary team conference from January 2015 to November 2021. Inclusion criteria were endophytic biopsy-proven T1 RCC treated with PCA with one year of follow-up. Complications were reported according to the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) classification system and the Clavien-Dindo classification (CDC) system. Major complications were defined as a grade ≥ 3 according to the CDC.ResultsFifty-six patients were included with a total of 56 endophytic tumors treated during 61 PCA sessions. The median RENAL nephrometry score was 9 (IQR 2), and the mean tumor size was 25.7 mm (SD ± 8.9 mm). Mean hospitalization time was 0.39 (SD ± 1.1) days. At a mean follow-up of 996 days (SD ± 559), 86% of tumors were recurrence free after one PCA. No patients progressed to metastatic disease. According to the CIRSE classification, 10.7% (n = 6) had grade 3 complications, and 5.4% (n = 3) had CDC major complications.ConclusionThis study demonstrates that PCA of endophytic biopsy-proven T1 RCC is safe with few major complications and excellent local tumor control rates at almost three-year mean follow-up.Level of Evidence 3Retrospective cohort study.Graphic

Central Neurocytoma Treated Using Supratentorial Ventricle Radiotherapy: A Single-Institution Analysis of Five Cases in Adjuvant or Salvage Settings After Surgery.

Central neurocytoma (CN) is an extremely rare tumor primarily located in the supratentorial ventricular system, categorized as a glioneuronal or neuronal tumor. This study presented a retrospective analysis of five CN patients who received adjuvant or salvage radiotherapy. Patients, aged 31-59 years, underwent radiation doses ranging from 60 Gy to 50.4 Gy over 27-30 fractions. All patients achieved effective local tumor control without severe complications. The median follow-up period was 51.7 months, demonstrating 100% overall and progression-free survival rates. Our study's clinical outcomes align with previous research, despite the limitation of a small sample size. Emphasizing the necessity for additional research, our findings added to the potential evidence of radiotherapy in managing CN. Larger, long-term studies were needed to confirm these promising results.

Indocyanine green-enhanced transpupillary thermotherapy for juxtapapillary retinal capillary hemangioblastoma.

To study the clinical presentation and treatment outcomes of indocyanine green-enhanced transpupillary thermotherapy (ICG-TTT) for treatment-naïve juxtapapillary retinal capillary hemangioblastoma (JRCH). A prospective interventional case series. The technique involved ICG dye infusion 45 seconds prior to application of TTT. The main study outcomes were local tumor control, resolution of subretinal fluid (SRF), and improvement in best-corrected visual acuity (BCVA). Eight eyes of seven patients (5 males and 2 females) were included. The mean age was 26 years (range: 5-56 years). Systemic evaluation revealed von-Hippel Lindau (VHL) disease in five patients. The most common location was the temporal aspect of the optic disc (5 eyes). The mean basal diameter was 2.9 mm (range: 1-8 mm), and tumor thickness was 1.4 mm (range: 1-4 mm). All eight eyes were treated with multiple sessions of ICG-TTT (mean: 3 sessions). Six eyes received adjuvant intravitreal injection of dexamethasone implant (4 eyes) and/or bevacizumab (4 eyes). Post treatment, six eyes (75%) had tumor regression with reduction of SRF. One eye had a partial response with persisting SRF, and one eye showed poor response to TTT for which external beam radiotherapy was performed. At the last follow-up (median: 11 months; range: 6-29 months), the BCVA remained stable in seven eyes and improved in one eye (hand motion to 20/40). Multiple ICG-TTT sessions can be considered as an alternative treatment option for JRCH with effective local tumor control and SRF resolution.

Image-Guided Thermal Ablation for Hepatic Epithelioid Hemangioendothelioma: A Multicenter Experience

PurposeTo investigate the feasibility, safety, and clinical outcomes of image-guided thermal ablation in patients with hepatic epithelioid hemangioendothelioma (HEHE). Materials and MethodsThis was a multicenter retrospective investigation of 18 patients (43.9 years [SD ± 14.8]; 6 men) who underwent image-guided thermal ablation for HEHE between January 2013 and February 2023. A total of 31 ablation sessions (24 involving microwave ablation and 7 involving radiofrequency ablation) were evaluated. The rates of technical success, adverse events, and outcomes were assessed. The Kaplan‒Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) rates. The risk factors affecting PFS were investigated using Cox proportional hazard regression analysis. ResultsThe technical success rate was 93.5% (29/31). No major adverse events occurred after ablation. Local tumor progression occurred in 2 sessions (6.5%, 2/31) after ablation, and intrahepatic distant metastasis occurred in 16 sessions (51.6%, 16/31). During the medium follow-up time of 37.2 months (range, 3–117 months), the OS and PFS rates were 87.6% and 62.2%, respectively, at 1 year; 75.5% and 37.4%, respectively, at 3 years; and 75.5% and 37.4%, respectively, at 5 years. The median OS and PFS were 90.5 months (95% CI: 68.1–112.8) and 23.8 months (95% CI: 15.4–32.2), respectively. According to the multivariate analysis, a larger tumor size (P = .026) was associated with shorter PFS. ConclusionsImage-guided thermal ablation is a feasible and safe treatment option for patients with HEHE that results in good local tumor control and a favorable long-term prognosis.