Combined Modality Research Articles

Synergistic Cellular Responses Conferred by Concurrent Optical and Magnetic Stimulation Are Attenuated by Simultaneous Exposure to Streptomycin: An Antibiotic Dilemma.

Concurrent optical and magnetic stimulation (COMS) combines extremely low-frequency electromagnetic and light exposure for enhanced wound healing. We investigated the potential mechanistic synergism between the magnetic and light components of COMS by comparing their individual and combined cellular responses. Lone magnetic field exposure produced greater enhancements in cell proliferation than light alone, yet the combined effects of magnetic fields and light were supra-additive of the individual responses. Reactive oxygen species were incrementally reduced by exposure to light, magnetics fields, and their combination, wherein statistical significance was only achieved by the combined COMS modality. By contrast, ATP production was most greatly enhanced by magnetic exposure in combination with light, indicating that mitochondrial respiratory efficiency was improved by the combination of magnetic fields plus light. Protein expression pertaining to cell proliferation was preferentially enhanced by the COMS modality, as were the protein levels of the TRPC1 cation channel that had been previously implicated as part of a calcium-mitochondrial signaling axis invoked by electromagnetic exposure and necessary for proliferation. These results indicate that light facilitates functional synergism with magnetic fields that ultimately impinge on mitochondria-dependent developmental responses. Aminoglycoside antibiotics (AGAs) have been previously shown to inhibit TRPC1-mediated magnetotransduction, whereas their influence over photomodulation has not been explored. Streptomycin applied during exposure to light, magnetic fields, or COMS reduced their respective proliferation enhancements, whereas streptomycin added after the exposure did not. Magnetic field exposure and the COMS modality were capable of partially overcoming the antagonism of proliferation produced by streptomycin treatment, whereas light alone was not. The antagonism of photon-electromagnetic effects by streptomycin implicates TRPC1-mediated calcium entry in both magnetotransduction and photomodulation. Avoiding the prophylactic use of AGAs during COMS therapy will be crucial for maintaining clinical efficacy and is a common concern in most other electromagnetic regenerative paradigms.

Clinical prognostic factors to guide treatment strategy for HPV‑positive oropharyngeal cancer using treatment outcomes of induction chemotherapy: A real‑world experience.

The role of induction chemotherapy (IC) in locally advanced oropharyngeal cancer (OPC) remains debatable, and suitable candidates for de-escalation treatment in these patients have not been fully identified. Therefore, the present study aimed to identify high-risk candidates for human papillomavirus (HPV)-positive OPC by analyzing patients who underwent IC followed by chemoradiotherapy (CRT) to guide optimal treatment strategies. Patients diagnosed with stage III-IVA OPC and treated with a minimum of two cycles of IC followed by CRT, between 2004 and 2020, were retrospectively reviewed. All the patients were restaged according to the American Joint Committee on Cancer, 8th edition. The overall response rate and survival outcomes associated with clinical factors based on HPV status were analyzed using univariate and multivariate analyses. The present study analyzed 105 patients with a median age of 60 years (range, 40-76 years). Among 105 patients, 40 (38.1%) were HPV-negative and 65 (61.9%) HPV-positive. In all patients, survival outcomes were notably poorer in patients aged ≥60 years (P=0.006) and those who did not achieve complete response post-CRT (P<0.001), irrespective of the HPV status. The median relative dose intensity of IC was ≥80%, indicating adequate treatment, regardless of age. In contrast to patients with HPV-negative OPC, age ≥60 years (P=0.011) and T4 stage (P=0.019) emerged as substantial poor prognostic factors for survival outcomes in patients with HPV-positive OPC. Patients with HPV-positive OPC were categorized into three groups based on the number of clinical factors at diagnosis (such as age and T4 stage). The progression-free and overall survival showed significant stratification across each group as the number of high-risk factors increased despite IC and CRT. The findings indicated that patients with these high-risk factors require a cautious therapeutic strategy even when they are diagnosed with HPV-positive OPC, and the role of combined modality, including IC, will need to be investigated in a randomized trial to be routinely incorporated into clinical practice.

Imaging of oral cavity and oropharyngeal masses: clinico-radiologic correlation

BackgroundClinical diagnosis of the masses of the oropharynx and the oral cavity is usually straightforward; however, deep extension of lesions should be assessed by imaging. Thirty patients with suspected masses in oral cavity and oropharynx were enrolled in the present study. Contrast-enhanced CT and MRI were used for imaging of all patients, and superficial ultrasound was used as screening (whether the mass was accessible to ultrasound or not). The aim of this study was to evaluate clinical impact of combined imaging modalities for assessment of intraoral and oropharyngeal masses.ResultsThere was a statistically significant difference between CT and MRI regarding the detected tumor size, lymph node and adjacent structures. CT had a sensitivity of 77.78% and specificity of 75% in the detection of malignancy. A low apparent diffusion coefficient can detect malignancy with 61.11% sensitivity and 91.67% specificity.ConclusionsThe radiographic diagnosis of the oral cavity presents a complex challenge. According to the unique presentation of each patient, combined CT and MRI imaging will enhance the identification and characterization of lesions in the oral cavity and oropharynx. There is a secondary, limited role for ultrasonography.

Miniaturized electromagnetic tracking enables efficient ultrasound-navigated needle insertions

Ultrasound (US) has gained popularity as a guidance modality for percutaneous needle insertions because it is widely available and non-ionizing. However, coordinating scanning and needle insertion still requires significant experience. Current assistance solutions utilize optical or electromagnetic tracking (EMT) technology directly integrated into the US device or probe. This results in specialized devices or introduces additional hardware, limiting the ergonomics of both the scanning and insertion process. We developed the first ultrasound (US) navigation solution designed to be used as a non-permanent accessory for existing US devices while maintaining the ergonomics during the scanning process. A miniaturized EMT source is reversibly attached to the US probe, temporarily creating a combined modality that provides real-time anatomical imaging and instrument tracking at the same time. Studies performed with 11 clinical operators show that the proposed navigation solution can guide needle insertions with a targeting accuracy of about 5 mm, which is comparable to existing approaches and unaffected by repeated attachment and detachment of the miniaturized tracking solution. The assistance proved particularly helpful for non-expert users and needle insertions performed outside of the US plane. The small size and reversible attachability of the proposed navigation solution promises streamlined integration into the clinical workflow and widespread access to US navigated punctures.

Overcoming Treatment Resistance in Medulloblastoma: Underlying Mechanisms and Potential Strategies.

Medulloblastoma is the most frequently encountered malignant brain tumor in the pediatric population. The standard of care currently consists of surgical resection, craniospinal irradiation, and multi-agent chemotherapy. However, despite this combination of multiple aggressive modalities, recurrence of the disease remains a substantial concern, and treatment resistance is a rising issue. The development of this resistance results from the interplay of a myriad of anatomical properties, cellular processes, molecular pathways, and genetic and epigenetic alterations. In fact, several efforts have been directed towards this domain and characterizing the major contributors to this resistance. Herein, this review highlights the different mechanisms that drive relapse and are implicated in the occurrence of treatment resistance and discusses them in the context of the latest molecular-based classification of medulloblastoma. These mechanisms include the impermeability of the blood-brain barrier to drugs, the overactivation of specific molecular pathways, the resistant and multipotent nature of cancer stem cells, intratumoral and intertumoral heterogeneity, and metabolic plasticity. Subsequently, we build on that to explore potential strategies and targeted agents that can abrogate these mechanisms, undermine the development of treatment resistance, and augment medulloblastoma's response to therapeutic modalities.

ATRT-18. ALISERTIB USED IN PEDIATRIC ATRT

Abstract BACKGROUND Atypical rhabdoid tumor (ATRT) is a rare and aggressive primary CNS tumor caused by variants or deletions in the tumor suppressor gene SMARCB1 (aka INI 1). SMARCB1 targets Aurora A kinase (AURKA), an important oncoprotein of the cell cycle. AURKA dysregulation can lead to genomic instability through its oncogenic effects. Alisertib is a selective AURKA inhibitor that has been explored for treatment in various cancers, including pediatric malignancies. METHODS Retrospective chart review of five patients diagnosed with ATRT, treated with Alisertib, at Nicklaus Children’s Hospital from 2019 - 2024. RESULTS of the 5 patients; three were females and two males, with a median age at diagnosis of 2 years. Only one patient had a germline mutation while the rest had somatic mutations. Prior to starting Alisertib therapy, all five patients received chemotherapy per multiple protocols; four patients underwent focal radiation therapy, three patients underwent resection, and two patients underwent tandem autologous transplants. All five patients were treated solely with Alisertib, median dose of 60 mg/m2 PO daily. Two patients had reduced doses during therapy secondary to cytopenia. One patient completed therapy over 13 months with partial response based on imaging. One patient presented progression of disease while on therapy and for that reason treatment was stopped. Three patients continue treatment: two with only Alisertib, one using Avastin and Sirolimus concurrently. CONCLUSIONS Prognosis in patients with ATRT is usually poor given its aggressive nature and high rate of recurrence despite intervention. It is important to note that treatment of ATRT is highly individualized and typically involves a combination of therapeutic modalities. While Alisertib is one of the newest treatment options, there’s limited literature of clinical improvement in patients with ATRT using this treatment. Therefore, further research on novel treatment options is warranted for the future.

Visual Field Prognosis From Macula and Circumpapillary Spectral Domain Optical Coherence Tomography.

To explore the structural-functional loss relationship from optic-nerve-head- and macula-centred spectral-domain (SD) Optical Coherence Tomography (OCT) images in the full spectrum of glaucoma patients using deep-learning methods. A cohort comprising 5238 unique eyes classified as suspects or diagnosed with glaucoma was considered. All patients underwent ophthalmologic examination consisting of standard automated perimetry (SAP), macular OCT, and peri-papillary OCT on the same day. Deep learning models were trained to estimate G-pattern visual field (VF) mean deviation (MD) and cluster MD using retinal thickness maps from seven layers: retinal nerve fiber layer (RNFL), ganglion cell layer and inner plexiform layer (GCL + IPL), inner nuclear layer and outer plexiform layer (INL + OPL), outer nuclear layer (ONL), photoreceptors and retinal pigmented epithelium (PR + RPE), choriocapillaris and choroidal stroma (CC + CS), total retinal thickness (RT). The best performance on MD prediction is achieved by RNFL, GCL + IPL and RT layers, with R2 scores of 0.37, 0.33, and 0.31, respectively. Combining macular and peri-papillary scans outperforms single modality prediction, achieving an R2 value of 0.48. Cluster MD predictions show promising results, notably in central clusters, reaching an R2 of 0.56. The combination of multiple modalities, such as optic-nerve-head circular B-scans and retinal thickness maps from macular SD-OCT images, improves the performance of MD and cluster MD prediction. Our proposed model demonstrates the highest level of accuracy in predicting MD in the early-to-mid stages of glaucoma. Objective measures recorded with SD-OCT can optimize the number of visual field tests and improve individualized glaucoma care by adjusting VF testing frequency based on deep-learning estimates of functional damage.

Effects of CE Ferulic® Combined with Microneedling in the Treatment of Pigmentary Disorders: A Monocentric, Split Face, Comparative Study

Pigmentary disorders of the face present a significant challenge in dermatology, impacting the confidence and well-being of affected individuals. Various approaches have been developed to address these concerns, including microneedling and topical vitamin C products. This study involved 15 participants undergoing three treatment sessions over 12 weeks, assessing the efficacy of a combined microneedling and CE Ferulic® serum approach. Clinical evaluation and statistical analysis were conducted before and after the intervention. Significant improvement of akin hyperpigmentation was observed, particularly on the side treated with microneedling and CE Ferulic® serum compared to microneedling alone. The integrated treatment protocol demonstrated a synergistic effect in improving skin texture and appearance. Integrated treatment protocols, such as combining microneedling with CE Ferulic® serum, show promise in managing facial hyperpigmentation disorders. Further research with larger cohorts is warranted to validate these findings and optimize treatment strategies, highlighting the potential of combined therapeutic modalities for achieving optimal clinical outcomes in pigmentary disorder management.

Predicting conversion from mild cognitive impairment to Alzheimer's disease: a multimodal approach.

Successively predicting whether mild cognitive impairment patients will progress to Alzheimer's disease is of significant clinical relevance. This ability may provide information that can be leveraged by emerging intervention approaches and thus mitigate some of the negative effects of the disease. Neuroimaging biomarkers have gained some attention in recent years and may be useful in predicting the conversion of mild cognitive impairment to Alzheimer's disease. We implemented a novel multi-modal approach that allowed us to evaluate the potential of different imaging modalities, both alone and in different degrees of combinations, in predicting the conversion to Alzheimer's disease of mild cognitive impairment patients. We applied this approach to the imaging data from the Alzheimer's Disease Neuroimaging Initiative that is a multi-modal imaging dataset comprised of MRI, Fluorodeoxyglucose PET, Florbetapir PET and diffusion tensor imaging. We included a total of 480 mild cognitive impairment patients that were split into two groups: converted and stable. Imaging data were segmented into atlas-based regions of interest, from which relevant features were extracted for the different imaging modalities and used to construct machine-learning models to classify mild cognitive impairment patients into converted or stable, using each of the different imaging modalities independently. The models were then combined, using a simple weight fusion ensemble strategy, to evaluate the complementarity of different imaging modalities and their contribution to the prediction accuracy of the models. The single-modality findings revealed that the model, utilizing features extracted from Florbetapir PET, demonstrated the highest performance with a balanced accuracy of 83.51%. Concerning multi-modality models, not all combinations enhanced mild cognitive impairment conversion prediction. Notably, the combination of MRI with Fluorodeoxyglucose PET emerged as the most promising, exhibiting an overall improvement in predictive capabilities, achieving a balanced accuracy of 78.43%. This indicates synergy and complementarity between the two imaging modalities in predicting mild cognitive impairment conversion. These findings suggest that β-amyloid accumulation provides robust predictive capabilities, while the combination of multiple imaging modalities has the potential to surpass certain single-modality approaches. Exploring modality-specific biomarkers, we identified the brainstem as a sensitive biomarker for both MRI and Fluorodeoxyglucose PET modalities, implicating its involvement in early Alzheimer's pathology. Notably, the corpus callosum and adjacent cortical regions emerged as potential biomarkers, warranting further study into their role in the early stages of Alzheimer's disease.

Brain age has limited utility as a biomarker for capturing fluid cognition in older individuals.

One well-known biomarker candidate that supposedly helps capture fluid cognition is Brain Age, or a predicted value based on machine-learning models built to predict chronological age from brain MRI. To formally evaluate the utility of Brain Age for capturing fluid cognition, we built 26 age-prediction models for Brain Age based on different combinations of MRI modalities, using the Human Connectome Project in Aging (n=504, 36-100 years old). First, based on commonality analyses, we found a large overlap between Brain Age and chronological age: Brain Age could uniquely add only around 1.6% in explaining variation in fluid cognition over and above chronological age. Second, the age-prediction models that performed better at predicting chronological age did NOT necessarily create better Brain Age for capturing fluid cognition over and above chronological age. Instead, better-performing age-prediction models created Brain Age that overlapped larger with chronological age, up to around 29% out of 32%, in explaining fluid cognition. Third, Brain Age missed around 11% of the total variation in fluid cognition that could have been explained by the brain variation. That is, directly predicting fluid cognition from brain MRI data (instead of relying on Brain Age and chronological age) could lead to around a 1/3-time improvement of the total variation explained. Accordingly, we demonstrated the limited utility of Brain Age as a biomarker for fluid cognition and made some suggestions to ensure the utility of Brain Age in explaining fluid cognition and other phenotypes of interest.

Ruptured pulmonary Echinococcus granulosus cyst: A rare cause of severe pneumogenic sepsis

Parasitic infections by Echinococcus granulosus are rare in Germany, and predominantly affect individuals with a migration background. Liver and lungs are the most commonly affected organs. Pulmonary cysts often remain asymptomatic until rupture, at which point symptoms may manifest. The diagnostic approach typically involves a combination of imaging modalities and serological tests, occasionally supplemented by molecular genetic methods. Given the global movements of migration, considerations of the epidemiology of common diseases in the country of origin should also be taken into account in the differential diagnosis. We present the unusual case of a pneumogenic sepsis in a young man from Syria, where the combination of medical history alongside radiological, serological, and molecular genetic investigations ultimately led to the diagnosis of a severe pulmonary echinococcosis with rupture.

A global multimodal flood event dataset with heterogeneous text and multi-source remote sensing images

ABSTRACT With the increasing frequency of floods, in-depth flood event analyses are essential for effective disaster relief and prevention. Satellite-based flood event datasets have become the primary data source for flood event analyses instead of limited disaster maps due to their enhanced availability. Nevertheless, despite the vast amount of available remote sensing images, existing flood event datasets continue to pose significant challenges in flood event analyses due to the uneven geographical distribution of data, the scarcity of time series data, and the limited availability of flood-related semantic information. There has been a surge in acceptance of deep learning models for flood event analyses, but some existing flood datasets do not align well with model training, and distinguishing flooded areas has proven difficult with limited data modalities and semantic information. Moreover, efficient retrieval and pre-screening of flood-related imagery from vast satellite data impose notable obstacles, particularly within large-scale analyses. To address these issues, we propose a Multimodal Flood Event Dataset (MFED) for deep-learning-based flood event analyses and data retrieval. It consists of 18 years of multi-source remote sensing imagery and heterogeneous textual information covering flood-prone areas worldwide. Incorporating optical and radar imagery can exploit the correlation and complementarity between distinct image modalities to capture the pixel features in flood imagery. It is worth noting that text modality data, including auxiliary hydrological information extracted from the Global Flood Database and text information refined from online news records, can also offer a semantic supplement to the images for flood event retrieval and analysis. To verify the applicability of the MFED in deep learning models, we carried out experiments with different models using a single modality and different combinations of modalities, which fully verified the effectiveness of the dataset. Furthermore, we also verify the efficiency of the MFED in comparative experiments with existing multimodal datasets and diverse neural network structures.

Combined modality for localized gastric diffuse large B-cell lymphoma: Long-term outcomes of 50 patients.

7079 Background: R-CHOP is the primary treatment for gastric diffuse large B-cell lymphoma (GDLBCL); for localized disease, the role of consolidative radiation therapy (RT) after chemotherapy remains underexplored. This study focuses on localized GDLBCL undergoing a combined modality therapy of R-CHOP followed by gastric RT, comparing outcomes between those receiving short-course (3-4 cycles) and full-course (6 cycles) R-CHOP. Methods: A retrospective analysis identified 50 consecutive PGDLBCL pts treated with R-CHOP followed by RT between 1/2000-1/2021. Baseline characteristics and follow-up data were collected. Lugano PET criteria and endoscopy (EGD) assessed overall response rate. Kaplan-Meier and univariable cox regression models estimated overall survival (OS) and (PFS). Results: Of the 50 pts with localized (Stage I-II) disease, 34 (68%) received 3-4 cycles of R-CHOP and 16 (32%) received 6 cycles. Pre-RT disease evaluation varied, with 36 (72%) undergoing EGD and PET, 4 (8%) EGD and CT, and 6 (12%) PET alone. One pt (3%) exhibited active DLBCL post 3-4 cycle R-CHOP, while 5 (31%) did so after 6 cycles (p=0.1). Median time from last R-CHOP dose to RT start date was 1.2 months with a median 3060 cGy delivered dose for both groups (range 2340-3060 in the 3-4 cycle group, 3000-4500 in the 6-cycle group). Median follow-up time from RT end is 58 months. No in-field failures occurred post-complete response (CR); however, 1 pt did not achieve a CR following R-CHOP and RT, progressing in the stomach and subsequently at new, out-of-field (OOF) sites. 3 pts had OOF progression without relapses in the stomach in a median time of 21 months. Low-grade lymphoma in the stomach post-DLBCL CR was observed in 2 pts, 3 and 22 months from RT end, with 1 OOF marginal zone lymphoma 2 years-post RT. OS and PFS did not significantly differ between the 3-4 and 6 cycle groups (96-month OS 70% vs. 86%, p=0.8; 96-month PFS 76% vs. 86%, p=0.7). OS and DLBCL PFS were analyzed for pts with evidence of residual DLBCL pre-RT compared to those without evidence of disease after R-CHOP. The 24-month DLBCL PFS was 92% in the CR group and 67% for those with incomplete response (p=0.14), with 92% and 67% 24-month survival probability (p=0.11). On univariate analysis, pre-RT evidence of active DLBCL by PET and/or EGD, pre-RT PET FDG uptake, and achieving CR on first-post-RT imaging were not statistically significant for DLBCL PFS. Conclusions: Recognizing the limitations of a retrospective study, our study documents the effectiveness of short-course R-CHOP followed by RT in localized GDLBCL, with similar outcomes to the full 6-cycle regimen. Excellent disease control was observed, with few instances of DLBCL or low-grade lymphoma relapse. Further analysis will include a cohort receiving R-CHOP alone without consolidative RT. This analysis aims to contribute to the evolving standard of care for GDLBCL, providing insights for future treatment strategies.

Descriptive analysis of brain metastases (BM) of solid neoplasms in an academic hospital from a low- and middle-income country (LMIC) with a Hispanic population.

e14015 Background: Multidisciplinary management of BM of solid cancers integrates different combinations of treatment modalities. The scarcity of SRS centers has prevented widespread adoption of this therapy for appropriately selected patients. Methods: One-hundred eighteen (51.7% female, 48.3% male, median age 59 years) BM patients from a National Health Institute from Mexico (INCMNSZ) were included and analyzed. Results: The most common primary tumors were lung and breast cancers (25 cases each, representing 21% of the whole cohort), kidney cancer (14%), male germ cell tumors (10%), metastatic carcinoma of unknown primary (CUP) (5%), upper- and lower- gastrointestinal cancers (5%), thyroid differentiated cancers (5%), followed by melanoma, prostate, ovarian, hepatobiliary cancers and sarcoma (3% each of them) and urothelial carcinoma (2%) being the least common. No biopsy was reported for only one case. The most common histomolecular tumors were adenocarcinoma of the lung (17 cases), renal cell carcinoma (17), triple negative (TN) breast cancer (BC) (9), HER-2+ BC (7), Nonseminomatous germ cell tumor (7), CUP (6), ER+/HER-2+ BC (5), Germ cell tumor with choriocarcinoma (5), small-cell lung cancer (SCLC) (5), melanoma (5), prostate adenocarcinoma (5), thyroid differentiated cancer not otherwise specified (NOS) (5). Rectal adenocarcinoma, high-grade serous ovarian cancer, ER+/PR+ BC, sarcomas and NSCLC (3 cases, each) and urothelial carcinoma (2). Rare tumor subtypes, with one case, each included hepatocellular carcinoma, PR+/HER2+ BC, follicular thyroid cancer, esophageal, gastric and colonic adenocarcinomas, neuroendocrine prostate, neuroendocrine gallbladder, endometrial, large cell neuroendocrine lung carcinomas and cholangiocarcinoma. A solitary BM was present in 44 patients (37.3%), 2-3 BM in 30 (25.4%) and &gt;3 BM in 44 patients (37.3%). 18 patients (15.2%) were not symptomatic at the time of diagnosis. 79 patients were treated with Whole-Brain Radiotherapy (WBRT), ten with a combination of surgery and adjuvant WBRT, seven with surgical resection without radiotherapy, only five included SRS as part of their treatment and seventeen received only supportive care. There was no difference in overall survival (OS) between treatment modalities excluding supportive care (p=0.05). Conclusions: Our experience from a LMIC with Hispanic population highlights that more than 50% of BM metastasize from solid tumors different from lung and breast cancers. Even though SRS has been included in recent guidelines from ASCO and ESMO, WBRT is the option most commonly included in multimodality treatments.

A single-arm, open-label phase II clinical trial of SHR-1210 (camrelizumab) in combination with nimotuzumab in the second-line treatment of advanced esophageal squamous cell carcinoma.

e16007 Background: The prognosis of advanced esophageal cancer is bleak, and the current first-line regimen based on paclitaxel, cisplatin and fluorouracil (TPF) with an effective rate is about 30%. The second-line treatment regimen based on anti-PD-1/PD-L1 monoclonal antibodies obtained median overall survival (mOS) 10.8 months in phase I-II clinical trials, but a large proportion of patients (pts) still do not respond to this therapy. Additionally, nimotuzumab in the previous Cuba phase 2 study had a good disease control rate (DCR) combined with PF regimen. So, we conducted the study to evaluate the new combination modality efficacy and treatment-related adverse events (safety). The primary endpoints was ORR, and the secondary endpoints included overall survival (OS), DCR, progression-free survival (PFS), duration of response (DoR), time to response (TTR), 9-month and 12-month survival rate, as well as safety. Methods: According to the relevant literature, the second-line treatment for ORR is about 15%, and the efficacy of camrelizumab combined with nimotuzumab is expected to be 35%, alpha=0.05. A total of 38 cases were enrolled in the two-stage Simon method, with a bilateral α value of 5% and a test efficiency of 90%. In the first phase, 23 pts were enrolled 15 pts in the second stage. If 9 or more pts reached CR/PR. The trial is considered successful. The dropout rate of 10% was calculated, and a total of 42 pts were enrolled. Results: In this phase 2 study, a total of 41 pts were administered. One case was lost to follow-up. The mean age was 45 years (range, 42-77). The results of the intention-to-treat analysis showed that the ORR was 36% (15/42). The mOS was 12.62 months with median follow-up 8.28 months. The 9-month and 12-month survival rates were 84% and 51%, respectively. The DCR was 81% (34/42). Median PFS was 9.89 months with median follow-up 9.17 months. In terms of safety, the incidence of TEAEs was 60% (25/42), of which 71% (30/42) had adverse events below grade 3 and 26% (11/42) had adverse events above grade 3 including 0 case related to nimotuzumab and 4 cases related to camrelizumab. The overall incidence of adverse drug reactions grade 3 or above was 10% (4/42), of which 0 case related to nimotuzumab and 4 cases related to camralizumab. Conclusions: The combination of camrelizumab and nimotuzumab in the second-line treatment of advanced esophageal squamous cell carcinoma showed a trend benefit for ORR and OS with a controllable toxicity.

Performance of a trained large language model to provide clinical trial recommendation in a head and neck cancer population.

11081 Background: Chatbots based on large language model (LLM) have demonstrated ability to answer oncology exam questions; however, leveraging LLM in medical-decision support have not yet demonstrated suitable performance in oncology practice. We evaluated the performance of a trained a LLM, GPT-4, to recommend appropriate clinical trials for a head &amp; neck (HN) cancer population. Methods: In 2022, we developed an artificial intelligence powered clinical trial management mobile app, LookUpTrials, and demonstrated promising user engagement among oncologists. Using LookUpTrials database, we applied direct preference optimization to train GPT-4 as an in-app assistant to LookUpTrials. From Nov 7 to Dec 19, 2023, we collected consecutive, new patient cases and their respective clinical trial recommendations from oncologists in the HN medical oncology service at Memorial Sloan Kettering Cancer Center. Cases were categorized by diagnosis, cancer stage, treatment setting, and physician recommendation on clinical trials. Trained GPT-4 is prompted using a semi-structured template: “Given patient with a &lt;diagnosis&gt;, &lt;cancer stage&gt;, &lt;treatment setting&gt;, what are possible clinical trials?” Physician recommendations were compared with trained GPT-4 responses. We analyzed the performance of GPT-4 based on its response precision (positive predictive value), recall (sensitivity), and F1 score (harmonic mean of precision and recall). Results: We analyzed 178 patient cases, mean age 65.6 (SD 13.9), primarily male (75%) with local/locally advanced (68%) HN (61%), thyroid (16%), skin (9%), or salivary (8%) cancers. Majority were treated in the definitive setting with combined modality therapy (42%) and modest proportion were treated under clinical trials (10%). Overall, trained GPT-4 achieved a moderate performance matching physician clinical trial recommendations with 63% precision and 100% recall (F1 score 0.77), narrowing a total list of 56 HN clinical trials to a range of 0-4 relevant trials per patient case (mean 1, SD 1.2). Comparatively, performance of our trained GPT-4 exceeded historic performance of untrained LLMs to provide oncology treatment recommendation by 4-20 folds (F1 score 0.04 - 0.19). Conclusions: This proof-of-concept study demonstrated that trained LLM can achieve moderate performance in matching physician clinical trial recommendation in HN oncology. Our results suggest the potential of embedding trained LLM into oncology workflow to aid clinical trial search and accelerate clinical trial accrual. Future research is needed to optimize precision of trained LLM and to assess whether trained LLM may be a scalable solution to enhance the diversity and equity of clinical trial participation.

P-GEMOX with sequential or sandwiched radiotherapy for early-stage extranodal natural killer/T-cell lymphoma.

7075 Background: Combined modality therapy (CMT), namely chemotherapy combined with radiotherapy, has been recommended for patients with localized extranodal natural killer/T-cell lymphoma (ENKTL). However, the optimal CMT has not been fully clarified. As chemotherapy is more easily accessible than immediate radiotherapy in the routine clinical practice, the “chemotherapy-first” CMT including sequential or sandwiched radiotherapy deserves further exploration. In addition, the optimal non-anthracycline-based regimen needs to be confirmed. Methods: The P-GEMOX regimen was administrated as follows: pegaspargase 2000 IU/m2 intramuscular on day 1, gemcitabine 1000 mg/m2 intravenous on day 1 and 8, oxaliplatin 130 mg/m2 intravenous on day 1 and was repeated every 21 days. Patients who achieved at least stable disease (SD) subsequently underwent involved field radiotherapy (IFRT). The dose of IFRT ranged from 50 to 55 Gy. Performing sequential radiotherapy (4 cycles of CT+RT) or sandwich radiotherapy (2 cycles of CT+RT+2 cycles of CT) is determined by the clinician based on the patients' conditions. The primary endpoint was the overall response rate (ORR) after 2 cycles of chemotherapy, and secondary study endpoints were CR, PFS, and OS. Safety was also evaluated. Results: From August 2020 to April 2023, thirty-seven patients (23 men, 14 women; median age: 55, 26-76 years) with stage I/II ENKTL who had received P-GEMOX were collected. 14 patients were stage IE and 23 were IIE. ALL patients completed at least 2 cycles of P-GEMOX, which resulted in 94.6% (35/37) of ORR including 30 patients with CR and 5 patients with PR. Among the patients in remission, 15 patients received sequential radiotherapy, 15 received sandwich radiotherapy, 4 were waiting for or in the process of radiotherapy, and 1 patient progressed before radiotherapy. With a median follow-up of 14.8 months (range: 2.6-38.1 months), the 3-year PFS and OS were 87.2% (95%CI 69.3%-95%) and 90.6% (95%CI 72%-97.1%), respectively. Sandwich radiotherapy had an obvious trend for longer PFS than sequential radiotherapy (18moths-PFS 100% vs. 78%; P=0.073). During the treatment, 21.6% (8/37) of the patients experienced grade 3–4 treatment-emergent adverse events (TEAEs). The most grade 3–4 hematological TEAEs were neutropenia (7/37, 18.9%) and thrombocytopenia (4/37, 10.8%). As for grade 3–4 non-hematological TEAEs, elevated aminotransferase, hyperbilirubinemia and hypofibrinogenemia were 16.2%, 10.8% and 8.1%, respectively. The adverse events of this CMT were well-tolerated and manageable. No treatment-related death occurred. Conclusions: Our study demonstrated that CMT consisted of P-GEMOX showed favorable efficacy with acceptable toxicity, and sandwich radiotherapy (CT+RT+CT) seems give more favorable PFS than sequential radiotherapy. The CMT protocol could be an effective treatment option for early-stage ENKTL patients.

Monocyte/lymphocyte ratio to predict immunoradiotherapy response in patients with advanced pretreated sarcoma.

e23523 Background: Immuno-radiotherapy may improve outcomes for patients with advanced solid tumors, although optimized combination modalities remain unclear. Here, we report the sarcoma cohort analysis from the SABR-PDL1 trial that evaluated the PD-L1 inhibitor atezolizumab in combination with stereotactic body radiation therapy (SBRT) in patients with advanced cancer. Methods: Eligible patients received atezolizumab 1200 mg every 3 weeks until progression or unmanageable toxicity, together with ablative SBRT delivered concurrently with the 2nd cycle (recommended dose of 45 Gy in 3 fractions, adapted upon normal tissue tolerance constraint). SBRT was delivered to at least one tumor site, with at least one additional measurable lesion being kept from the radiation field. The primary efficacy endpoint was one-PFS rate from the start of atezolizumab. Sequential tumor biopsies were collected for deep multi-feature immune profiling and monocyte/lymphocyte ratio (sum of cells derived from the monocytic lineage including monocytes, macrophages and myeloid dendritic cells, divided by sum of lymphocytes) were computed both on tumor and blood. Results: 61 highly pretreated (median of 5 prior lines) patients with advanced sarcomas (leiomyosarcoma: 28% and other types; 32 men [53%]; median age, 47 years [range, 37-55 years]) were enrolled in two centers (France; Spain) from 03/2020 to 04/2021. All but one received atezolizumab and 56/61 (92%) received SBRT. The most frequently irradiated site was lung (n = 36/72 lesions; 50%). Treatment-related G3 (no G4-5) toxicity was observed in one (2%) patient. Median OS and PFS were respectively 12.2 [95%CI:7-18.4] and 2.5 months [95%CI:1.2-2.6], including five (8.2%) patients with PFS &gt; 1 year. Best overall responses consisted of PR (n = 3;5%) and SD (n = 36; 60%). Altogether, 182 (n = 86 paraffin; n = 96 freshly frozen) sequential tumor biopsies from 35 patients were successfully analyzed. None (0%) of the biopsies harbored tertiary-lymphoid structures. Tumor RNA sequencing analysis using independent immune deconvolution technics including CIBERSORTabs, EPIC and xCELL revealed an increased tumor infiltration of monocytic lineage-derived cells in patients who rapidly progressed. Differential gene expression analysis showed a significant upregulation of genes implicated in immunosuppression in unressponsive tumors. Unresponsive tumors were enriched with immune chemoattractants. We found higher monocyte/lymphocyte ratio in unresponsive patients compared to patients who had stable disease or tumor response both in the tumor and in the blood. Matched blood and tumor monocyte/lymphocyte ratios were significantly correlated in this population. Conclusions: This study provides new data on the feasibility, efficacy, and immune context of tumors that may help identifying patients with advanced sarcomas most likely to respond to immuno-radiotherapy. Clinical trial information: NCT02992912 .

Contemporary radiation therapy use in Hodgkin lymphoma

Radiation therapy assumes a pivotal role in Hodgkin lymphoma management, especially within combined modality therapy. It serves as a cornerstone in early-stage disease and in mitigating high-risk instances of local relapse in advanced stages. Over recent decades, radiation therapy has undergone significant advancements, notably alongside diagnostic imaging improvements, facilitating the reduction of radiation field size and dosage. This progress has notably led to minimized toxicity while upholding treatment efficacy.This comprehensive review extensively evaluates the indications and advancements in radiation therapy for Hodgkin lymphoma, with a primary focus on enhancing treatment efficacy while minimizing radiation-related toxicities. The exploration encompasses a detailed examination of various radiation fields, techniques and delivery modalities employed in Hodgkin lymphoma treatment, including intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), and proton therapy. It delves into the intricacies of optimal dose selection and treatment planning strategies aimed at achieving maximal disease control while concurrently minimizing the risk of long-term side effects.

Use of Different Anti-PD-1 Checkpoint Combination Strategies for First-Line Advanced NSCLC Treatment-The Experience of Ion Chiricuță Oncology Institute.

Different combination modalities between an anti-PD-1/PD-L1 agent and a platinum-based chemotherapy or another checkpoint inhibitor (with or without a short course or full course of a platinum doublet) proved superior to chemotherapy alone in multiple clinical trials, but these strategies were not directly compared. The aim of this study is to report the real-world data results with different immunotherapy combinations in a series of patients treated in consecutive cohorts at the Ion Chiricuță Oncology Institute. A total of 122 patients were successively enrolled in three cohorts: (1A) nivolumab + ipilimumab (18 patients), (1B) nivolumab + ipilimumab + short-course chemotherapy (33 patients), and (2) pembrolizumab plus full-course chemotherapy (71 patients). Endpoints included overall survival (OS), progression-free survival (PFS), objective response (ORR), and univariate and multivariate exploratory analysis of prognostic factors. Median follow-up in the consecutive cohorts 1A, 1B, and 2 was 83 versus 59 versus 14.2 months. Median OS and PFS for all patients were 22.2 and 11.5 months, respectively, and 2-year actuarial OS and PFS were 49% and 35%, respectively. For the nivolumab + ipilimumab (cohorts 1A and 1B) versus pembrolizumab combinations (cohort 2), median OS was 14 vs. 24.8 months (p = 0.18) and 2-year actuarial survival 42% vs. 53%; median PFS was 8.6 vs. 12.7 months (p = 0.41) and 2-year actuarial PFS 34% vs. 35%; response rates were 33.3% vs. 47.9% (p = 0.22). Older age, impaired PS (2 versus 0-1), corticotherapy in the first month of immunotherapy, and >3.81 neutrophils to lymphocytes ratio were independent unfavorable prognostic factors in the multivariate analysis of survival (limited to 2 years follow-up). The 5-year long-term survival was 30.5% and 18.8% for cohorts 1A and 1B, respectively (not enough follow-up for cohort 2). Efficacy results using different immunotherapy combination strategies were promising and not significantly different between protocols at 2 years. Real-world efficacy and long-term results in our series were in line with those reported in the corresponding registration trials.