Local Control Research Articles

Efficacy and Safety of Donut-Shaped Circumferential Spine CyberKnife Stereotactic Body Radiotherapy for Metastatic Spine Disease.

Spinal metastases (SM) with epidural spinal cord compression (ESCC) present a significant challenge because of the high risk of radiation-induced injury to critical structures such as the spinal cord and nerve roots. Traditional treatment approaches often avoid circumferential stereotactic body radiotherapy (SBRT) to reduce these risks. The efficacy and safety of donut-shaped circumferential SBRT, designed to target the spinal column while sparing the spinal cord, remains underexplored. The aim of this study was to evaluate the safety and efficacy of donut-shaped circumferential CyberKnife SBRT for SM, particularly in preventing radiation-induced myelopathy and achieving local tumor control (LTC). We retrospectively analyzed data from patients treated with donut-shaped circumferential SBRT between 2014 and 2023. Key parameters examined included patient demographics, ESCC grade (Bilsky), prior treatments, clinical symptoms, and treatment parameters. We focused on SBRT dosimetric data, radiation exposure to the spinal cord and cauda equina, adherence to dose-volume constraints, and post-SBRT outcomes, including myelopathy and LTC. Forty-eight lesions in 43 patients (median age: 65; range: 20-78) were reviewed. One patient required separation surgery for severe ESCC (Bilsky grade 3). The median clinical target volume was 63.77 cm3, and the median margin dose was 24 Gy. Over a median follow-up of 8 months, LTC was 91.1% at 6 months, 87.1% at 1 year, 82.8% at 3 years, and 62.1% at 5 years. The median overall survival was 17 months. Of the 21 lesions exceeding dose constraints, only one patient exhibited clinical myelopathy, which correlated with local tumor recurrence. No radiographic myelopathy or other radiation-induced complications were observed. Donut-shaped circumferential CyberKnife SBRT is a safe and effective treatment of SM, achieving high LTC with minimal radiation-induced complications, including myelopathy.

Clinical outcomes and prognostic indicators in parotid gland carcinomas: a single-center experience.

Parotid gland cancers (PGC) are a heterogeneous group with different histological types and grades. This difference has implications for patient management and adjuvant treatment decisions. This study aims to determine the poor prognostic factors affecting local control and survival in PGC. A retrospective review of 42 patients treated for malignant parotid masses between January 2008 and December 2023. Risk factors analyzed included sex, age, histological grade, tumor size, stage, nodal involvement, perineural invasion (PNI), surgical margins, and additional treatments. Of the 42 patients, 47.6% were male, and the median age was 44years. The 5-year local relapse-free survival (LRFS) was 69.7%. Positive surgical margins significantly associated with lower LRFS rate (p=.007). The 5-year disease-specific survival (DSS) was 83.9%, with surgical margin and T stage being significant prognostic factors (0.044 and 0.031, respectively). Advanced T stage was associated with a higher rate of preoperative facial nerve dysfunction (p=.004). This study underscores the critical role of comprehensive diagnostic and individualized surgical strategies in the treatment of parotid gland malignancies.

Inflammatory conditions shape phenotypic and functional characteristics of lung-resident memory T cells in mice

Lung tissue-resident memory T cells (TRM) are critical for the local control of respiratory tract infections caused by influenza A viruses (IAV). Here we compare TRM populations induced by intranasal adenoviral vector vaccines encoding hemagglutinin and nucleoprotein (NP) with those induced by an H1N1 infection in BALB/c mice. While vaccine-induced TRM express high levels of CD103 and persist longer in the lung parenchyma, short-lived, H1N1-induced TRM have a transcriptome associated with higher cytotoxic potential and distinct transcriptional profile as shown by single-cell RNA sequencing. In both the vaccine and H1N1 groups, NP-specific CD8+ T cells expand during heterologous influenza virus infection and protect the mice from disease. Meanwhile, lung inflammation in response to an infection with unrelated respiratory syncytial virus do not influence the fate of pre-existing TRM. Our preclinical work thus confirms that inflammatory conditions in the tissue shape the phenotypic and functional characteristics of TRM to serve relevant informations for optimizing mucosal vaccines.

Stereotactic radiosurgery for vestibular schwannomas in neurofibromatosis type 2: a systematic review and meta-analysis

BackgroundManagement of neurofibromatosis type 2 (NF2)- associated vestibular schwannomas (VSs) is challenging due to their multiplicity, early onset, proximity to the brainstem, unpredictable growth, and aggressive behavior. The optimal therapeutic intervention remains controversial in the literature, and the advantages and disadvantages of each treatment option should be evaluated for each patient. Stereotactic radiosurgery (SRS) has exhibited favorable results in the management of NF2-associated VSs. This systematic review and meta-analysis aimed to assess the role of SRS in NF2-associated VSs.MethodsOn August 22, 2024, four electronic databases, comprising PubMed, Embase, Scopus, and Web of Science, were comprehensively searched. Studies that assessed SRS’s radiological and clinical outcomes in NF2-associated VSs were enrolled.ResultsNineteen studies were included with 960 individuals and 1310 NF2-associated VSs. The analysis showed a pooled local control (LC) rate of 83% (95%CI:74-90%). Older age (P = 0.001), prior resection (P = 0.003), and lower tumor volume (P = 0.019) were associated with higher LC rates. The results demonstrated a pooled serviceable hearing preservation (SHP) rate of 42% (95%CI:34-51%), trigeminal nerve worsening rate of 2% (95%CI:1-4%), and a facial nerve worsening rate of 5% (95%CI:2-9%). None of the patients experienced radionecrosis (RN) following SRS. Sensitivity analyses revealed a moderate to high robustness of the results. No publication bias was identified.ConclusionSRS is an effective therapeutic modality for managing VSs, especially small—to medium-sized lesions. We showed that SRS is associated with favorable LC and SHP rates and considerably low trigeminal or facial nerve worsening and RN rates.

Impact of brain metastasis size at the time of radiotherapy on local control and radiation necrosis.

No consensus has been reached regarding whether upfront versus deferred radiation to small, asymptomatic brain metastases is most optimal. We sought to assess the relationship between tumor size at radiation and subsequent development of local recurrence and radiation necrosis to make data-driven recommendations regarding timing of radiation utilization. We identified 2268 patients with 6308 newly diagnosed brain metastases between 2010 and 2022 managed with brain-directed radiotherapy at Brigham and Women's Hospital/Dana-Farber Cancer Institute (Boston, MA). Tumors were grouped by maximal unidimensional size: <0.5cm, 0.5 to < 1cm, 1cm to < 2cm, and ≥ 2cm; local recurrence and radiation necrosis by tumor size were assessed using competing risks regression. Among metastases initially treated with stereotactic radiation or whole brain radiotherapy, lesions 1 to < 2cm (HR 2.30 [95% CI, 1.38-3.81], p = 0.001 and HR 2.61 [95% CI 1.76-3.89], p < 0.001, respectively) and ≥ 2cm (HR 3.10 [95% CI, 1.62-5.94], p < 0.001 and HR 3.03 [95% CI 1.92-4.79], p < 0.001, respectively) displayed greater local recurrence compared to tumors < 0.5cm. In addition, among patients treated with stereotactic radiation, significantly higher risk of radiographic and symptomatic necrosis was observed in tumors ≥ 0.5cm versus < 0.5cm at radiotherapy, with hazard ratios ranging from 3.27 to 18.90. Larger metastasis size is associated with markedly poorer local control and increased necrosis following brain-directed radiation, suggesting a role for earlier utilization of radiation therapy in patients with small, asymptomatic metastases and a favorable prognosis.

Verteporfin-Mediated In Situ Nanovaccine Based on Local Conventional-Dose Hypofractionated Radiotherapy Enhances Antitumor and Immunomodulatory Effect.

In situ radiotherapy is the most successful cytotoxic therapy available for the treatment of solid tumors, while high-dose radiotherapy per fraction is not yet widely and reliably used. To some extent, the major considerations of the disappointing results are on the risk of high-dose irradiation-induced damage to the surrounding normal tissues and the difficulty in distant metastasis control. To break these restraints, a gelatinase-responsive amphiphilic methoxypolyethyleneglycol-PVGLIG-polycaprolactone (mPEG-PVGLIG-PCL) nanoparticles' loading verteporfin (N@VP), a special photosensitizer that can also be excited by X-rays to produce cytotoxic singlet oxygen and greatly enhance radiotherapy efficacy, is prepared in this study. Herein, it is shown that the formed N@VP combined with conventional-dose radiation therapy (RT, 2 Gy (gray, a radiation dose unit)) can realize an antitumor effect no less than high-dose RT (8 Gy) and minimize radiation dose necessary to achieve local tumor control. Moreover, this radiosensitive nanosystem can exert excellent systemic antitumor immunity and abscopal effect, providing a preferable "in situ vaccine" strategy based on conventional-dose RT to achieve efficient systemic management of distant tumor metastasis. When combined with immunotherapy, this novel strategy for radiosensitization results in better immunotherapy sensitivity by stimulating significant immunogenic tumor cell death and synergistic antitumor immune responses.

Comparison of outcomes between total en bloc spondylectomy and palliative spinal surgery in metastatic spinal tumor patients: propensity score matching analysis

BackgroundTotal en bloc spondylectomy (TES) was considered aggressive spinal surgery aim to achieved marginal and wide surgical margin in spinal tumor treatment. However, there was limited comparison information between TES and other palliative spinal surgery treatments. This study aimed to report the comparison between TES and Palliative Spinal Surgery (PSS) in terms of clinical and oncologic outcomes.MethodsA retrospective cohort study was conducted. The medical records of Spinal Metastasis (SM) treated by a single surgeon were reviewed between January 2014 and December 2020. The propensity score matching was calculated. survivorship, local recurrence, surgical complications, operative blood loss, and time between TES and PSS were reviewed and analyzed.ResultsA total of 44 patients with a mean age of 56 were included. Twenty-two TES and 22 PSS patients were recruited into the study—no significant difference in demographics data. The TES showed significantly better survival at 6 (p = 0.010) and 12 months (p = 0.020). The local recurrence in the TES group was 4.6% (1 of 22). However, TES showed significantly longer operative time (6 h (5.5–6.5) and 3 h (2.0-3.5), p-value < 0.001) and more intraoperative blood loss (1150 mL (1000–1800) and 575 mL (350–800), p-value = 0.0002).ConclusionsTES showed better survivorship after 6 and 12 months than PSS. The TES also achieved favorable local control of tumors after surgery. Further randomized control of more patients should be conducted to clarify the benefits of TES vis-à-vis metastasis.

Combination radiation and αPD-L1 enhance tumor control by stimulating CD8+ PD-1+ TCF-1+ T cells in the tumor-draining lymph node

Combination radiotherapy (RT) and αPD-L1 therapy has potential to enhance local and distant (abscopal) tumor control, however, clinical results in humans have been variable. Using murine melanoma models, we found RT + αPD-L1 increases intra-tumor progenitor CD8+ PD-1+ TCF-1+ T cells. This increase depends on trafficking of the PD-1+ TCF-1+ cells from the tumor-draining lymph node (TdLN) to the tumor. RT alone promotes the expansion and differentiation of the TdLN derived PD-1+ TCF-1+ cells into TIM-3+ GZMB+ TCF-1- effector-like cells in the tumor with further enhancement after the addition of αPD-L1. In the TdLN, combination therapy enriches for a novel PD-1+ TCF-1+ TOX- LY6A+ subset with expression of a type I interferon and migratory signature. This subset is able to traffic to the tumor and differentiate into TIM-3+ TCF-1- cells. Finally, we found that ablation of the PD-1+ TCF-1+ T cell population attenuates the enhanced tumor control observed with combination RT + αPD-L1. These results suggest that abscopal response failures may be secondary to impaired stimulation of TdLN CD8+ PD-1 + TCF-1+ T cells or an inability of PD-1+ TCF-1+ cells in the TdLN to traffic to the tumor.

Stereotactic body radiation therapy for spinal metastases from gastrointestinal primary cancers.

Metastases from gastrointestinal (GI) primary cancers are considered relatively radioresistant. This study is one of the largest to evaluate outcomes following stereotactic body radiation therapy (SBRT) for GI cancer spinal metastases and supplements its findings with a review of the literature. A prospectively maintained single-institution database of spinal metastases treated with SBRT was analyzed. Seventy-five patients with 106 GI primary cancer spinal metastases were identified. The median single-fraction dose was 16Gy (interquartile range (IQR): 14-16). Multi-fraction regimens ranged from 18 to 35Gy over 2-5 fractions. Median follow-up was 5 months (IQR: 1-13). Cumulative incidence rates of 3-, 6-, and 12-month local failure (LF) were 5%, 9%, and 10%, respectively. Rates of 12-month LF were 6% for gastroesophageal, 10% for hepatobiliary, and 13% for colorectal cancers. Multilevel tumors ≥ 2 vertebrae were associated with LF (p = 0.006, HR: 5.61, 95% CI: 1.61-19.5). Rates of 3-, 6-, and 12-month overall survival (OS) were 68%, 50%, and 41%, respectively. Multivariable analysis showed epidural disease associated with inferior OS (p = 0.037, HR: 1.75, 95% CI: 1.04-2.96). Complete or partial pain responses for 93 tumors (88%) presenting with pain were 60%, 51%, 32%, and 32% after 1, 3, 6, and 12 months, respectively. Ten vertebral compression fractures (9%) developed following treatment. Twelve radiation toxicities (11%) were observed, with no cases of neuropathy or myelopathy. SBRT offers effective local tumor control and pain palliation with minimal toxicity for GI cancer spinal metastases, whose incidence is expected to rise with advances in screening and systemic therapies.

Living donor liver transplantation for neo-adjuvant treated, unresectable intrahepatic cholangiocarcinoma (LIVINCA): study protocol for a one-armed, mono-centric, non-randomized trial.

Background Intrahepatic cholangiocarcinoma has demonstrated a consistently increasing incidence in recent years. In cases of unresectability, palliative chemotherapy often remains the only option, typically associated with a poor prognosis. Liver transplantation might be an option for otherwise unresectable intrahepatic cholangiocarcinoma. We aim to conduct a prospective, non-randomized study to further explore the effects of living-donor liver transplantation in the treatment of unresectable neoadjuvant treated intrahepatic cholangiocarcinoma. Methods Patients with unresectable intrahepatic cholangiocarcinoma having a stable disease or tumor regression after systemic chemotherapy without an extrahepatic tumor burden are suitable for study inclusion. For a local control of the tumor, an additional local-ablative therapy in means of a selective internal radio-therapy is mandatory. The main concept of the surgical procedure is a liver transplantation using the left (segments II - IV) or the right lobe (segments V - VIII) of a living donor. In oncosurgical optimal conditions, a two-staged hepatectomy combined with the (initially) auxiliary transplantation of a left-lateral lobe of a living donor is the possible. Results The patient recruitment will start in September 2024. Conclusion The design of the LIVINCA study may provide patients with otherwise unresectable intrahepatic cholangiocarcinoma a chance for a curative treatment option. This procedure does not reduce the deceased donor organ supply because living donation is the primary treatment option in these patients. Trial registration Registered at Clinical Trials; NCT06539377; registered on August 6, 2024.

Results of the Latin American Pediatric Oncology Group (GALOP) Trial for Patients With Metastatic Ewing Sarcoma: Multicentric study of Interval-Compressed Multiagent and Metronomic Chemotherapy.

GALOP investigators developed a multicenter protocol to standardize treatment for newly diagnosed metastatic Ewing sarcoma (ES) in South America. Prospective trial. Induction chemotherapy consisted of 9 alternating interval-compressed cycles (every 14 days) of vincristine, doxorubicin, cyclophosphamide, and ifosfamide-etoposide; local and metastatic site control; and 5 consolidation cycles (every 21 days), followed by MCT with cyclophosphamide and vinblastine for 1 year. Between 2011 and 2019, 198 patients were recruited from 34 centers in Argentina, Brazil, Chile, and Uruguay. Characteristics include: male patients (60.6%), median age of 12.3 years (range, 0.8-31.1); axial primary localization (62.1%), size >8 cm (70.2%); and bone origin (71.2%). Metastatic sites were lung, extra-lung, and combined in 43.4%, 31.3%, and 25.3%, respectively. The overall response rate was 79.3%, and local treatment was performed in 85.3% of patients. With a median follow-up of 65.1 months (95% CI: 53.9-76.4), the 5-year overall survival (OS) and event-free survival (EFS) were 33.1% (95% CI: 25.9-40.4) and 27.8% (95% CI: 21.5-34.3), respectively. The 5-year OS was 44.9%, 31.3%, and 15.6% for lung, extra-lung, and combined, respectively (p < 0.001). The median interval between induction chemotherapy cycles was 17 days, with a febrile neutropenia rate of 19.3%. Metronomic chemotherapy (MCT) was administered to 100 patients (50.5%), demonstrating good tolerability, with 58 patients completing at least 75% of the scheduled cycles. The implementation of a multicenter protocol incorporating MCT for metastatic ES proved feasible across Latin America.

Immune Modulation Through Stereotactic Radiotherapy: The Role of TBX21, GATA-3, FoxP3, and RORɣt

Background and Objectives: Stereotactic radiotherapy enhances local tumor control by delivering high doses directly to the tumor. It is thought to activate the immune system via T-cells, possibly creating a systemic response. This study aims to evaluate stereotactic body radiotherapy’s (SBRT) impact on the immune system by measuring T-cell transcription factors, such as TBX21, GATA-3, FoxP3, and RORɣt. Materials and Methods: Peripheral blood samples were collected from 103 patients before SBRT and from 66 patients two months post-treatment. We measured transcription factors TBX21, GATA-3, FOXP3, and RORγt using ELISA, and performed a complete blood count and C-reactive protein analysis to rule out infections. Statistical analyses included paired t-tests and correlation analyses to assess changes before and after treatment. Results: Post-treatment, significant reductions were observed in TBX21 (Th1), GATA-3 (Th2), and FOXP3 (Treg), while RORɣt (Th17) remained stable but trended higher in lung cancer patients. No correlations were found with demographic factors. However, TBX21 levels were significantly related to the planning target volume (PTV) and biologically effective dose (BED10) in the lung region. Larger PTVs (≥16.5 cc) and higher BED10 doses (≥100 Gy) were linked to smaller reductions in TBX21 (p = 0.008, p = 0.04) and increased RORɣt levels (p = 0.01). Conclusions: Stereotactic radiotherapy reduces immunosuppressive markers like FOXP3 and GATA-3, indicating its potential to boost immune activation by suppressing Treg and Th2 cells. Larger target volumes and higher BED10 values may enhance Th1 responses through TBX21. These findings suggest that SBRT activates the immune system, and its combination with immunotherapy could be promising.

Carbon Ion Radiotherapy in the Head and Neck Cancers Treatment and its Potential Role in Personalized Treatment Approach- A Review of the Current Knowledge.

Head and neck cancer (HNC) is a complex, heterogeneous group of malignancies. In treatment a combined modality therapy with surgery, radiotherapy and chemotherapy is usually advised. The use of charged particles was a breakthrough in radiation oncology and allowed the initiation of cancer treatment with high-precision. The purpose of the work is to discuss the role of carbon ion radiotherapy in the treatment of head and neck cancers. Heavy ions such as carbon have more favorable physical and radiobiological properties than photons. The unique properties of carbon ions enable radiotherapy with dose escalation to tumors, while reducing both, radiation dose to adjacent normal tissues and radiation area. Considering its exceptional features, carbon ion radiotherapy offers promising results with acceptable toxicity regarding treatment of uncommon and rare malignancies, especially treated for a recurrent disease. HNC patients with adenoid cystic carcinoma and mucosal melanoma of the head and neck, which are considered to be radiation resistant, should benefit more from carbon ion radiotherapy than proton beam therapy or conventional photon radiotherapy. Also selected patients with other head and neck malignancies can benefit form carbon ion radiotherapy including advanced salivary gland cancer and nasopharyngeal cancer patients. Carbon ion radiotherapy offers better dose distributions, higher tumor doses, and an increased odds of local control and prolonged survival. Carbon ion radiotherapy represents a promising alternative to conventional photon RT or even proton beam therapy especially in treatment of radioresistant tumors situated close to critical organs.

Local Conditional Controlling for Text-to-Image Diffusion Models

Diffusion models have exhibited impressive prowess in the text-to-image task. Recent methods add image-level structure controls, e.g., edge and depth maps, to manipulate the generation process together with text prompts to obtain desired images. This controlling process is globally operated on the entire image, which limits the flexibility of control regions. In this paper, we explore a novel and practical task setting: local control. It focuses on controlling specific local region according to user-defined image conditions, while the remaining regions are only conditioned by the original text prompt. However, it is non-trivial to achieve it. The naive manner of directly adding local conditions may lead to the local control dominance problem, which forces the model to focus on the controlled region and neglect object generation in other regions. To mitigate this problem, we propose Regional Discriminate Loss to update the noised latents, aiming at enhanced object generation in non-control regions. Furthermore, the proposed Focused Token Response suppresses weaker attention scores which lack the strongest response to enhance object distinction and reduce duplication. Lastly, we adopt Feature Mask Constraint to reduce quality degradation in images caused by information differences across the local control region. All proposed strategies are operated at the inference stage. Extensive experiments demonstrate that our method can synthesize high-quality images aligned with the text prompt under local control conditions.

Hypo-fractionated versus single-session radiosurgery to preserve hearing in patients affected by sporadic vestibular schwannoma. The ACOUNEU randomized clinical trial.

Hypo-fractionated versus single-session radiosurgery to preserve hearing in patients affected by sporadic vestibular schwannoma. The ACOUNEU randomized clinical trial.

Reconfigurable Three‐Dimensional Superconducting Nanoarchitectures

AbstractWhen materials are patterned in 3D, there exist opportunities to tailor and create functionalities associated with an increase in complexity, the breaking of symmetries, and the introduction of curvature and non‐trivial topologies. For superconducting nanostructures, the extension to the third dimension triggers the emergence of new physical phenomena, and lead to advances in technologies. Here, 3D nanopatterning is harnessed to fabricate and control the emergent properties of a 3D superconducting nanostructure. Not only are the existence and motion of superconducting vortices demonstrated in 3D but, with numerical simulations, it is shown that the confinement leads to well‐defined bending of the vortices within the volume of the structure. This 3D confinement manifests experimentally in a strong geometrical anisotropy of the critical field, through which the reconfigurable coexistence of superconducting and normal states in the 3D superconducting architecture, and the local definition of weak links, are achieved. In this way, an intermediate regime of nanosuperconductivity is uncovered, where the vortex state is truly 3D and can be designed and manipulated by geometrical confinement. This insight into the influence of 3D geometries on superconducting properties offers a route to local reconfigurable control for future computing devices, sensors, and quantum technologies.

DiMSOD: A Diffusion-Based Framework for Multi-Modal Salient Object Detection

Multi-modal salient object detection (SOD) through the integration of additional data such as depth or thermal information has become a significant task in computer vision during recent years. Traditionally, the challenges of identifying salient objects in RGB, RGB-D (Depth), and RGB-T (Thermal) images are tackled separately. However, without intricate cross-modal fusion strategies, such approaches struggle to effectively integrate multi-modal information, often resulting in poorly defined object edges or overconfident inaccurate predictions. Recent studies have shown that designing a unified end-to-end framework to handle all three types of SOD tasks simultaneously is both necessary and difficult. To address this need, we propose a novel approach that treats multi-modal SOD as a conditional mask generation task utilizing diffusion models. We introduce DiMSOD, which enables the concurrent use of local (depth maps, thermal maps) and global controls (original images) within a unified model for progressive denoising and refined prediction. DiMSOD is efficient, only requiring fine-tuning of our newly introduced modules on the existing stable diffusion, which not only reduces the fine-tuning cost, making it more viable for practical use, but also enhances the integration of multi-modal conditional controls. Specifically, we have developed modules including SOD-ControlNet, Feature Adaptive Network (FAN), and Feature Injection Attention Network (FIAN) to enhance the model's performance. Extensive experiments demonstrate that DiMSOD efficiently detects salient objects across RGB, RGB-D, and RGB-T datasets, achieving superior performance compared to previous well-established methods.

Editing Memories Through Few Targeted Neurons

Model editing is a novel research topic in large language models (LLMs), aimed at efficiently handling various knowledge editing tasks. Since irrelevant knowledge is difficult to measure, existing editing methods often lack explicit ways to preserve it, especially for editing methods based on the fine-tuning paradigm. They generally control the locality performance of model editing by constraining the range of changes in model parameters. However, their performance improvements are not always ideal, and may even lead to a decrease in the editing reliability. In this paper, we try to explore effective editing locality control methods based on the relationship between the stored knowledge and the strongly associated model components. Based on the discovery of ``knowledge neurons'' and enough experimental results, we further explore the potential characteristics between knowledge and model components, confirm and point out: (1) only 1% neurons have significant contributions to specific knowledge storage, and (2) these targeted neurons often have a high overlap for knowledge with similar relational descriptions, which means that knowledge with similar relationships may be severely affected when these targeted neurons are modified. Based on these findings, we propose Targeted Neurons Fine-tuning with Data Augmentation (TNF-DA), which performs data augmentation based on the relational representation of edited knowledge to improve editing locality. By freezing most of the model parameters and only fine-tuning the highly contributing neurons corresponding to the edited knowledge, we obtain desirable results in terms of generalization and specificity compared with previous fine-tuning-based methods. Extensive experiments have demonstrated the superior editing performance achieved by our proposed method.

Stereotactic Body Radiation Therapy Alone or in Combination with Immunotherapy in Kidney Cancer: A Systematic Review.

Stereotactic Body Radiation Therapy Alone or in Combination with Immunotherapy in Kidney Cancer: A Systematic Review.

Nonoperative Management of Technically Resectable Pancreatic Cancer With Ablative Radiation Therapy

Surgical resection of pancreatic ductal adenocarcinoma (PDAC) modestly improves long-term survival due to the competing risk of metastatic disease. However, postoperative morbidity often interferes with administration of systemic therapy and may be unacceptable to some patients. Ablative radiation therapy (A-RT) has emerged as an effective noninvasive local treatment in many tumor types and may provide an alternative to surgery in select patients with resectable PDAC. To estimate the efficacy of A-RT in technically resectable PDAC. This cohort study of consecutive patients with histologically confirmed, radiographically resectable T1-2N0-1M0 PDAC treated with A-RT at Memorial Sloan Kettering Cancer Center between June 2016 and December 2022 were included from a prospectively maintained database. Patients were not eligible for surgery because of noncancer-related comorbidities. Data were frozen for analysis in December 2023, which took place between March and November 2024. All patients received A-RT exceeding 97.5-Gy biologically effective dose with daily computed tomography or magnetic resonance imaging guidance, motion management, and daily or selective adaptation of the dose distribution. The primary outcome was overall survival (OS). Secondary outcomes included biochemical and radiographic objective response rate, cumulative incidence of local progression, progression-free survival, and distant metastasis-free survival. Of 25 patients with radiographically resectable PDAC who received A-RT, 13 (52%) were male, and the median (IQR) age at time of A-RT was 80 (74-87) years. A total of 20 patients (80%) had a Karnofsky Performance Status score of 80 or lower. A total of 15 tumors (60%) were T2, and 4 (16%) were node positive. A total of 17 patients (68%) received induction chemotherapy for a median (range) of 2.9 (1.0-6.1) months. Radiation therapy regimens delivered with conventional linear accelerators included 75 Gy in 25 fractions among 13 patients, 67.5 Gy in 15 fractions among 9 patients, 50 Gy in 5 fractions among 2 patients (magnetic resonance imaging-guided linear accelerator), and 60 Gy in 10 for 1 patient. OS, local progression, and distant metastasis-free survival at 2 years were 43.7% (95% CI, 27.4%-69.5%), 20.8% (95% CI, 7.3%-39.0%), and 20.0% (95% CI, 9.1%-43.8%), respectively. Grade 3 acute and late gastrointestinal tract toxic effects were noted in 3 and 1 patients, respectively, with no grade 4 or higher events. In this cohort study, A-RT in patients with technically resectable PDAC led to effective local tumor control and favorable OS despite advanced age, poor Karnofsky Performance Status score, and conservative use of chemotherapy in the cohort studied. These data support a prospective study of A-RT for the management of resectable PDAC.