Tumor Location Research Articles

First Bite Syndrome in Transoral Surgery for Oropharyngeal Cancer.

First bite syndrome (FBS) is a rare complication of transoral surgery (TOS) for oropharyngeal cancer (oropharyngeal squamous cell carcinoma [OPSCC]). Risk factors for developing this complication are not well described. In this study, we attempt to identify risks for developing FBS in TOS. Retrospective chart review. Tertiary care medical center. This study was exempted by the Mayo Clinic institutional review board. We performed a review from January 2017 to November 2022 of all patients who underwent TOS for OPSCC by a single provider. Exclusion criteria included less than 6 months follow up, prior treatment of head and neck cancer, or incomplete records. Demographic data, comorbidities, tumor characteristics, surgical details, adjuvant treatment details, functional outcomes, and oncologic outcomes were assessed. Fisher's Exact test and Kruskal-Wallis rank sum test were used to identify significant variables, and multivariable logistic regression was used to address confounding. One hundred andone patients were identified. Eighty-nine met the inclusion criteria. The mean follow-up was 34 months (median 33). Seven patients (7.9%) developed FBS. Palatine tumor primary (P = .041), resection of styloglossus/stylopharyngeus (P = .039), and parapharyngeal fat manipulation (P = .015) were associated with the presence of FBS. After adjusting for tumor location, manipulation of parapharyngeal fat maintained significance (P = .025). T and N staging, tumor volume, adjuvant radiation, and ligation of lingual/facial arteries were not associated with the development of FBS. Eighty-six percent(6/7) of patients had aresolution of FBS at an average of 11.3 months. Manipulation of the parapharyngeal space is independently associated with developing FBS in TOS in our cohort. Further confirmatory studies are warranted.

Newly Designed Quasi-intrinsic Photosensitizers for Fluorescence Image-Guided Two-Photon Photodynamic Therapy with Type I/II Photoreactions.

In this work, a set of quasi-intrinsic photosensitizers are theoretically proposed based on the 2-amino-8-(1'-β-d-2'-deoxyribofuranosyl)-imidazo[1,2-α]-1,3,5-triazin-4(8H)-one (P), which could pair with the 6-amino-5-nitro-3-(1'-β-d-2'-deoxyribofuranosyl)-2(1H)-pyridone (Z) and keep the essential structural characters of nucleic acid. It is revealed that the ring expansion and electron-donating/electron-withdrawing substitution bring enhanced two-photon absorption and bright photoluminescence of these monomers, thereby facilitating the selective excitation and tumor localization through fluorescence imaging. However, instead of undergoing radiative transition (S1 → S0), the base pairing induced fluorescence quenching and rapid intersystem crossing (S1 → Tn) are observed and characterized by the reduced singlet-triplet energy gaps and large spin-orbit coupling values. To ensure the phototherapeutic properties of the considered base pairs in long-lived T1 state, we examined the vertical electron affinity as well as vertical ionization potential for production of superoxide anions via Type I photoreaction, and their required T1 energy (0.98 eV) to generate singlet oxygen 1O2 via Type II mechanism.

A Computational Framework for the Administration of 5-Aminovulinic Acid Before Glioblastoma Surgery.

5-Aminolevulinic Acid (5-ALA) is the only fluorophore approved by the FDA as an intraoperative optical imaging agent for fluorescence-guided surgery in patients with glioblastoma. The dosing regimen is based on rodent tests where a maximum signal occurs around 6h after drug administration. Here, we construct a computational framework to simulate the transport of 5-ALA through the stomach, blood, and brain, and the subsequent conversion to the fluorescent agent protoporphyrin IX at the tumor site. The framework combines compartmental models with spatially-resolved partial differential equations, enabling one to address questions regarding quantity and timing of 5-ALA administration before surgery. Numerical tests in two spatial dimensions indicate that, for tumors exceeding the detection threshold, the time to peak fluorescent concentration is 2-7h, broadly consistent with the current surgical guidelines. Moreover, the framework enables one to examine the specific effects of tumor size and location on the required dose and timing of 5-ALA administration before glioblastoma surgery.

Survival after Resection of Malignant Peripheral Nerve Sheath Tumors: introducing and validating a novel type-specific prognostic model

Abstract Background This study aimed to assess the performance of currently available risk calculators in a cohort of patients with malignant peripheral nerve sheath tumors (MPNST) and to create an MPNST-specific prognostic model including type-specific predictors for overall survival (OS). Methods This is a retrospective multicenter cohort study of patients with MPNST from eleven secondary or tertiary centers in The Netherlands, Italy and the USA. All patients diagnosed with primary MPNST who underwent macroscopically complete surgical resection from 2000-2019 were included in this study. A multivariable Cox proportional hazard model for OS was estimated with pre-specified predictors (age, grade, size, NF-1 status, triton status, depth, tumor location and surgical margin). Model performance was assessed for the Sarculator and PERSARC calculators by examining discrimination (C-index) and calibration (calibration plots and observed-expected statistic; O/E-statistic). Internal-external cross-validation by different regions was performed to evaluate the generalizability of the model. Results A total of 507 patients with primary MPNSTs were included from 11 centers in 7 regions. During follow-up (median 8.7 years), 211 patients died. The C-index was 0.60 (95% CI 0.53-0.67) for both Sarculator and PERSARC. The MPNST-specific model had a pooled C-index of 0.69 (95%CI 0.65-0.73) at validation, with adequate discrimination and calibration across regions. Conclusions The MPNST-specific MONACO model can be used to predict 3-, 5-, and 10-year OS in patients with primary MPNST who underwent macroscopically complete surgical resection. Further validation may refine the model to inform patients and physicians on prognosis and support them in shared decision-making.

Risk factors for domain-specific neurocognitive outcome in pediatric survivors of a brain tumor in the posterior fossa - Results of the HIT 2000 trial.

Neurocognition can be severely affected in pediatric brain tumor survivors. We analyzed the association of cognitive functioning with radiotherapy dose, postoperative cerebellar mutism syndrome (pCMS), hydrocephalus, intraventricular methotrexate (MTX) application, tumor localization and biology in pediatric survivors of a posterior fossa tumor. Subdomain-specific neurocognitive outcome data from 279 relapse-free survivors of the HIT-2000 trial (241 medulloblastoma and 38 infratentorial ependymoma) using the Neuropsychological Basic Diagnostic (NBD) tool based on Cattell-Horn-Carroll's model for intelligence were analyzed. Cognitive performance 5.14 years (mean; range=1.52-13.02) after diagnosis was significantly below normal for all subtests. Processing speed and psychomotor abilities were most affected. Influencing factors were domain-specific: CSI-dose had strong impact on most subtests. pCMS was associated with psychomotor abilities (β=-0.25 to -0.16) and processing speed (β=-0.32). Postoperative hydrocephalus correlated with crystallized intelligence (β=-0.20) and short-term memory (β=-0.15), age with crystallized intelligence (β=0.15) and psychomotor abilities (β=-0.16 and β=-0.17). Scores for fluid intelligence (β=-0.23), short-term memory (β=-0.17) and visual processing (β=-0.25) declined, and scores for selective attention improved (β=0.29) with time after diagnosis. Dose of CSI was strongly associated with neurocognitive outcome. Low psychomotor abilities and processing speed both in patients treated with and without CSI suggest a strong contribution of the tumor and its surgery on these functions. Future research therefore should analyze strategies to both reduce CSI-dose and toxicity caused by other treatment modalities.

Emerging Treatments Targeting the Tumor Microenvironment for Advanced Chondrosarcoma.

Chondrosarcoma (ChS), a malignant cartilage-producing tumor, is the second most frequently diagnosed osseous sarcoma after osteosarcoma. It represents a very heterogeneous group of malignant chemo- and radiation-resistant neoplasms, accounting for approximately 20% of all bone sarcomas. The majority of ChS patients have a good prognosis after a complete surgical resection, as these tumors grow slowly and rarely metastasize. Conversely, patients with inoperable disease, due to the tumor location, size, or metastases, represent a great clinical challenge. Despite several genetic and epigenetic alterations that have been described in distinct ChS subtypes, very few therapeutic options are currently available for ChS patients. Therefore, new prognostic factors for tumor progression as well as new treatment options have to be explored, especially for patients with unresectable or metastatic disease. Recent studies have shown that a correlation between immune infiltrate composition, tumor aggressiveness, and survival does exist in ChS patients. In addition, the intra-tumor microvessel density has been proven to be associated with aggressive clinical behavior and a high metastatic potential in ChS. This review will provide an insight into the ChS microenvironment, since immunotherapy and antiangiogenic agents are emerging as interesting therapeutic options for ChS patients.

Outcomes after laparoscopic or open liver resection for nonalcoholic fatty liver disease-associated hepatocellular carcinoma: a propensity score-matching study.

Laparoscopic liver resection (LLR) is rapidly gaining popularity; however, its efficacy for nonalcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC) (NAFLD-HCC) has been not evaluated. The purpose of this study was to compare short- and long-term outcomes between LLR and open liver resection (OLR) among patients with NAFLD-HCC. We used a single-institution database to analyze data for patients who underwent LLR or OLR for NAFLD-HCC from January 2007 to December 2022. We performed propensity score-matching analyses to compare overall postoperative complications, major morbidities, duration of surgery, blood loss, transfusion, length of stay, recurrence, and survival between the two groups. Among 210 eligible patients, 46 pairs were created by propensity score matching. Complication rates were 28% for OLR and 11% for LLR (p = 0.036). There were no significant differences in major morbidities (15% vs. 8.7%, p = 0.522) or duration of surgery (199 min vs. 189 min, p = 0.785). LLR was associated with a lower incidence of blood transfusion (22% vs. 4.4%, p = 0.013), less blood loss (415 vs. 54 mL, p < 0.001), and shorter postoperative hospital stay (9 vs. 6 days, p < 0.001). Differences in recurrence-free survival and overall survival between the two groups were not statistically significant (p = 0.222 and 0.301, respectively). LLR was superior to OLR for NAFLD-HCC in terms of overall postoperative complications, blood loss, blood transfusion, and postoperative length of stay. Moreover, recurrence-free survival and overall survival were comparable between LLR and OLR. Although there is a need for careful LLR candidate selection according to tumor size and location, LLR can be regarded as a preferred treatment for NAFLD-HCC over OLR.

Predicting therapeutic clinical trial enrollment for underrepresented patients in neuro-oncology using supervised machine learning.

1614 Background: Despite the unique ability of machine learning (ML) techniques to uncover complex interactive effects in datasets, studies exploring predictors of clinical trial enrollment have largely used standard statistical methods to discern associations. Furthermore, there have been limited applications of ML to close existing disparities in clinical trial enrollment of underrepresented patients in neuro-oncology. This study aims to use supervised machine learning to define and validate primary contributors of therapeutic clinical trial enrollment for a) all patients, b) women and c) NIH-designated minority patients with low- and high-grade glioma. Methods: Adult glioma patients who received care from the UCSF Brain Tumor Center between 1997- 2017 were identified in a prospective registry. Bootstrap forest (BF) and Recursive Partitioning (RP) models were created by randomly dividing patients in a 70/30 split into development (DEV) and validation (VAL) cohorts among all patients, women, and NIH-designated minority patients, separately. Model performance was assessed using the area under the curve (AUC) in the DEV and VAL cohorts. Results: Among 1042 patients, 350 patients (33.6%) enrolled in a therapeutic clinical trial. There were 445 women (42.7%), of which 144 (32.4%) enrolled, and 141 minority patients (13.5%), of which 39 (27.7%) enrolled. For all patients, in order of decreasing influence, the BF model selected median neighborhood household income, age, neighborhood poverty level, distance from hospital, tumor location, tumor volume, treatment with chemotherapy, occupation, KPS, insurance status, employment status, seizure at presentation, and volumetric extent of resection (EOR) to predict trial enrollment (DEV AUC: 0.984; VAL AUC: 0.746). For women, the BF model selected distance from hospital, age, household income, neighborhood poverty level, tumor location, treatment with chemotherapy, and KPS for trial prediction (DEV AUC: 0.972; VAL AUC: 0.746), whereas for minority patients, the BF model selected neighborhood poverty level, age, occupation, distance from hospital, tumor volume, insurance status, employment status, and EOR to predict trial enrollment (DEV AUC: 0.9830; VAL AUC: 0.769). The RP model for women designated those with non-White race as less likely to enroll (DEV AUC: 0.735; VAL AUC: 0.665) while the RP model for minority patients characterized those who preferred a non-English language or who were divorced or widowed as less likely to enroll (DEV AUC: 0.775; VAL AUC: 0.601). Conclusions: Supervised machine learning models achieved similar predictive performance among patient subgroups, while uncovering interactions between gender identity, minority status, and sociodemographic variables. These findings can guide targeted recruiting efforts to advance equitable trial enrollment for women and minorities.

Genetic Prognostic Factors in Adult Diffuse Gliomas: A 10-Year Experience at a Single Institution.

Gliomas are primary brain lesions involving cerebral structures without well-defined boundaries and constitute the most prevalent central nervous system (CNS) neoplasms. Among gliomas, glioblastoma (GB) is a glioma of the highest grade and is associated with a grim prognosis. We examined how clinical variables and molecular profiles may have affected overall survival (OS) over the past ten years. A retrospective study was conducted at Sina Hospital in Tehran, Iran and examined patients with confirmed glioma diagnoses between 2012 and 2020. We evaluated the correlation between OS in GB patients and sociodemographic as well as clinical factors and molecular profiling based on IDH1, O-6-Methylguanine-DNA Methyltransferase (MGMT), TERTp, and epidermal growth factor receptor (EGFR) amplification (EGFR-amp) status. Kaplan-Meier and multivariate Cox regression models were used to assess patient survival. A total of 178 patients were enrolled in the study. The median OS was 20 months, with a 2-year survival rate of 61.0%. Among the 127 patients with available IDH measurements, 100 (78.7%) exhibited mutated IDH1 (IDH1-mut) tumors. Of the 127 patients with assessed MGMT promoter methylation (MGMTp-met), 89 (70.1%) had MGMT methylated tumors. Mutant TERTp (TERTp-mut) was detected in 20 out of 127 cases (15.7%), while wildtype TERTp (wildtype TERTp-wt) was observed in 107 cases (84.3%). Analyses using multivariable models revealed that age at histological grade (p < 0.0001), adjuvant radiotherapy (p < 0.018), IDH1 status (p < 0.043), and TERT-p status (p < 0.014) were independently associated with OS. Our study demonstrates that patients with higher tumor histological grades who had received adjuvant radiotherapy exhibited IDH1-mut or presented with TERTp-wt experienced improved OS. Besides, an interesting finding showed an association between methylation of MGMTp and TERTp status with tumor location.

Evolving Standards of Care in the Management of Localized Colorectal Cancer.

The treatment of patients with localized rectal cancer is complex and requires input from a multidisciplinary team. Baseline local staging and mismatch repair protein testing are vital to develop individualized treatment plans. There are multiple options in terms of treatment modalities and sequencing, including transanal excision, short-course radiation, long-course chemoradiation, chemotherapy doublet or triplet, nonoperative management, and immune checkpoint blockade for patients with mismatch repair deficient tumors. While localized colon cancer is typically treated with surgical resection and consideration of adjuvant chemotherapy, emerging data suggest that neoadjuvant chemotherapy may be beneficial in patients with higher-risk disease. Quality-of-life considerations are imperative to prevent potential chronic effects on psychosocial health, neuropathy, fertility, and bowel, bladder, and sexual function. The omission of radiation or surgery can mitigate these toxicities without diminishing oncologic outcomes. The optimal treatment plan and sequence is not a one-size-fits-all approach but rather should be personalized to the patient's disease burden, tumor location, comorbidities, and preferences.

Targeted treatment in inflammatory myofibroblastic tumors in children.

10046 Background: Inflammatory myofibroblastic tumors (IMTs) and epithelioid inflammatory myofibroblastic sarcoma (EIMS)-a variant of IMT, are rare mesenchymal neoplasms in children. Surgical resection has been the mainstay of treatment, however it may cause morbidities due to the size, location, invasiveness of the tumor. With the identification of targetable molecular alterations, targeted treatment has begun to be used in inoperable/relapsed/refractory cases. Methods: Files of children with IMT diagnosed and treated between 1990-2023 were retrospectively evaluated for demographic, clinical, molecular characteristics, treatment and outcome. Results: The mean age of 8 patients (5 male, 3 female) at diagnosis was 9 years (8 months-17 years). Six had IMT and two EMS. Tumor localization was intestine, retroperitoneum, lower extremity in two patients each; liver and back in one each. None had metastatic at diagnosis. Three of the six patients (one EMS) who underwent only surgical resection had negative surgical margins (one after re-resection) and are under follow-up with no evidence of disease (NED). Molecular analysis was performed in six patients. ALK was positive in the tumor tissue of five patients. One patient with an inoperable local recurrence received chemotherapy, had a life-threatening infection and resistant hypercalcemia. The molecular analysis by next-generation sequencing revealed a YWHAE-ROS fusion and she was treated by ceritinib, after which a significant (&gt;90%) tumor shrinkage occurred and hypercalcemia resolved. She is currently in remission and continuing treatment. The patient with a positive surgical margin experienced local and metastatic (lung, liver) recurrences during follow-up and was treated with chemotherapy containing vincristine, actinomycin-D, and cyclophosphamide, the patient died due to progressive disease. In a patient with an unresectable tumor and ALK positivity, crizotinib treatment was initiated. After a treatment duration of seven months with crizotinib, the tumor completely regressed and treatment was stopped. On follow-up, local recurrence was detected after two months of cessation of crizotinib, crizotinib was restarted, considering the infiltrative appearance of the tumor and possible morbidities if operated. Two months after readministering crizotinib, complete response was achieved once again. The patient is continuing treatment with crizotinib. Thus, 7/8 patients are alive with NED for a median of 99 (9-174) months. Conclusions: Inflammatory myofibroblastic tumor and epithelioid inflammatory myofibroblastic sarcoma are rare in children. Surgery is the mainstay of treatment. The effectiveness of chemotherapy is yet unclear despite its use in inoperable cases. Molecular analysis of tumor tissue is highly recommended as targets such as ALK rearrangements or ROS fusions may enable the use of targeted treatments with fewer side effects.

State-of-the-Art Management of Colorectal Cancer: Treatment Advances and Innovation.

Colorectal cancer (CRC) remains a significant global health challenge, ranking among the leading causes of cancer-related morbidity and mortality worldwide. Recent advancements in molecular characterization have revolutionized our understanding of the heterogeneity within colorectal tumors, particularly in the context of tumor sidedness. Tumor sidedness, referring to the location of the primary tumor in either the right or left colon, has emerged as a critical factor influencing prognosis and treatment responses in metastatic CRC. Molecular underpinnings of CRC, the impact of tumor sidedness, and how this knowledge guides therapeutic decisions in the era of precision medicine have led to improved outcomes and better quality of life in patients. The emergence of circulating tumor DNA as a prognostic and predictive tool in CRC heralds promising advancements in the diagnosis and monitoring of the disease. This innovation facilitates better patient selection for exploration of additional treatment options. As the field progresses, with investigational agents demonstrating potential as future treatments for refractory metastatic CRC, new avenues for enhancing outcomes in this challenging disease are emerging.

Epidemiological profile of Ophir Loyola Cancer Hospital: A snapshot of the incidence of solid neoplasms in the eastern Amazon.

e22515 Background: The geographical distribution of cancer is a major concern in global public health, associated with this reality, the susceptibility of a population is closely linked to risk factors and carcinogenic profiles in different groups, which explain the heterogeneous prevalence and incidences among countries. In Brazil the region delimited by the Legal Amazon has a distinct epidemiological profile with a high prevalence of breast cancer and a low survival rate compared to countries with the highest human development index. Furthermore, the North and The Northeast has more than half of the country's penile cancer cases. In Pará, Ophir Loyola Cancer Hospital(OLCH) accounts for 71.11% of hospital visits in the state. The results of this study indicate the importance of OLCH as the reference center in Pará for the care and treatment of cancer patients. Methods: This was an ecological, exploratory, and mixed descriptive studythat investigated the epidemiological profile of patients with cancer treated at OLCH from January to December 2020. Sociodemographic data at admission were the primary variables, which were analyzed according to spatial distribution. Results: In this study, the data of 2952 patients were analyzed, with the majority being between the ages of 50 and 79 years (62.47%), and diagnosed but without previous treatment (87.30%). The most common cancers were breast (16.50%), cervical (13.40%), stomach (8.98%), and prostate (7.72%). The spatial distribution of the total number of cases, by the location of the primary solid tumor, was heterogeneous with regard to the number of cases per municipality. In Tucuruí Lake and Carajás, thyroid cancer was the second most frequent neoplasms, and in the Lower Amazon, it was the third most frequent . Previous studies have indicated the high mining activity in Carajás and the Lower Amazon with a strong relationship between methyl mercury and Mercury contamination in the Tapajós River and the adjacent gold extraction territory and and fish contamination. In some regions of Pará, cervical cancer is more prevalent than breast câncer in womans, which is different from the national data where it ranks second or third in the female population. Within the relationship between females and males, there was a higher proportion of cases of stomach cancer among men, representing the second more prevalent tumor in men, indicating a high incidence of gastric cancer in the region. Conclusions: The care profile at OLCH showed a high incidence of solid malignancies compared to other regions of Brazil, such as gastric cancer, cervical and thyroid cancer, indicating environmental and sociocultural influences on the carcinogenic profile present in the Eastern Amazon. Just as a heterogeneous incidence of tumors was seen in the regions of Pará.

Therapeutic Outcome of Multidisciplinary Treatment in Unresectable Biliary Tract Cancer: A Multicenter Retrospective Analysis.

There is little established evidence regarding treatment strategies for unresectable biliary tract cancer (BTC). This study aimed to clarify the situation of multidisciplinary treatment for unresectable BTC in the 2000s when there was no international standard first-line therapy. We retrospectively reviewed 315 consecutive patients with unresectable BTC who had been treated at seven tertiary institutions in Kanagawa Prefecture, Japan between 1999 and 2008. The unresectable factors were as follows: locally advanced, 101 cases (32.1%); hematogenous metastases, 80 cases (25.4%); and peritoneal dissemination, 30 cases (9.5%). Chemotherapy or radiation therapy was administered to 218 patients (69.2%). The best supportive care was provided in 97 cases (30.8%). The most common regimen was gemcitabine monotherapy, followed by gemcitabine combination therapy and S-1 monotherapy. The 1- and 2-year survival rates of all patients were 34.6% and 12.2%, respectively. The median survival time (MST) was 8 months in all patients. The 1-year survival rate was 65%, and the MST was 12 months among the locally advanced patients, whereas patients with peritoneal dissemination had the worst outcome; the 1-year survival rate was 7%, and the MST was 5 months. Among treated 90 cases of perihilar cholangiocarcinoma, patients who received chemoradiotherapy (n = 24) had a significantly better outcome than those who received chemotherapy alone (MST: 20 vs. 11 months, P < 0.001). Unresectable BTC has heterogeneous treatment outcomes depending on the mode of tumor extension and location. Multidisciplinary treatment seems useful for patients with locally advanced BTC, whereas patients with metastatic disease still have a poor prognosis.

Radiologic-Pathologic Correlation of Cardiac Tumors: Updated 2021 WHO Tumor Classification.

Cardiac tumors, although rare, carry high morbidity and mortality rates. They are commonly first identified either at echocardiography or incidentally at thoracoabdominal CT performed for noncardiac indications. Multimodality imaging often helps to determine the cause of these masses. Cardiac tumors comprise a distinct category in the World Health Organization (WHO) classification of tumors. The updated 2021 WHO classification of tumors of the heart incorporates new entities and reclassifies others. In the new classification system, papillary fibroelastoma is recognized as the most common primary cardiac neoplasm. Pseudotumors including thrombi and anatomic variants (eg, crista terminalis, accessory papillary muscles, or coumadin ridge) are the most common intracardiac masses identified at imaging. Cardiac metastases are substantially more common than primary cardiac tumors. Although echocardiography is usually the first examination, cardiac MRI is the modality of choice for the identification and characterization of cardiac masses. Cardiac CT serves as an alternative in patients who cannot tolerate MRI. PET performed with CT or MRI enables metabolic characterization of malignant cardiac masses. Imaging individualized to a particular tumor type and location is crucial for treatment planning. Tumor terminology changes as our understanding of tumor biology and behavior evolves. Familiarity with the updated classification system is important as a guide to radiologic investigation and medical or surgical management. ©RSNA, 2024 Supplemental material is available for this article.

Evaluation of tumor immune microenvironment for PD-L1 score and tumor infiltrating lymphocytes in high grade osteosarcomas and their correlation with disease progression.

e23510 Background: Tumor Immune Micro-environment is being increasingly recognised as a potential target for improving overall survival for osteosarcomas, especially in the metastatic setting. Our study purpose was to evaluate the PD- L1 (Programmed cell Death- Ligand 1) expression in neoplastic cells well as Tumor Infiltrating Lymphocyte (TIL) density of osteosarcoma specimens and correlate it with oncological outcomes. Materials &amp; Methods: A prospective cohort study was conducted between March 2017 and March 2022 among osteosarcoma patients who underwent primary biopsy and neo-adjuvant chemotherapy followed by surgical excision at our centre. We excluded patients who had alternative diagnoses such as low grade osteosarcoma, secondary osteosarcoma, recurrent osteosarcoma as well as patients who had undergone initial treatment (chemotherapy/ surgery) outside our institute. De-paraffinized sections (4μ) incubated with primary antibody (PDL1) and a universal secondary detection kit used. Average percentage of positive cells calculated from at least 10 representative fields at 400X magnification. Positive staining was considered when ≥1% cells showed positivity. IHC scoring of PD-L1 was graded as negative, low positive and high positive. We calculated the number of TILs under 400X magnification in ten fields and then took their average. TILs staining was scored semi quantitatively using a 3 tiered scale. Results: Forty patients who fulfilled the inclusion &amp; exclusion criteria were included in the study with most common age group being 10 to 19 years (27 patient, 68%). The male: female ratio was 1.6: 1 and the most common location of tumor was distal femur. Majority of patients had the histological subtype of conventional osteosarcoma (37 patients, 92.5%). Lung metastasis was present at time of initial diagnosis in 27 patients (67.5%). At the end of 2 years, 27 patients were alive (60%) while 13 patients had died due to disease. PD-L1 expression was negative in 17.5%, low positive in 15% and high positive in 67.5%. Among TIL category, 19 patients belonged to category 1, 10 belonged to category 2 &amp; 11 belonged to category 3. There was significant correlation between PD-L1 expression score &amp; TIL category. PD-L1 score did not correlate with percentage of necrosis following chemotherapy, metastasis on presentation or overall survival. Conclusions: PD-L1 score had significant correlation with density of Tumor Infiltrating lymphocytes (TIL). However, PD-L1 score did not correlate with overall survival, tumor-free survival, progression of metastasis or local recurrence.

Real-world clinical effectiveness and treatment patterns in the early-stage esophageal/gastroesophageal junction cancer (EC/GEJC) population treated in the community oncology setting in the United States.

e23273 Background: Definitive chemoradiotherapy (dCRT) is the recommended treatment for patients with early-stage EC/GEJC not eligible for surgery. There have been improvements with treatment for esophageal cancer, but the overall 5-year survival rates remain low at approximately 20%. This study examined patient characteristics, current treatment patterns and outcomes with dCRT regimens in the US community oncology setting. Methods: This was a retrospective observational cohort study using structured and unstructured electronic health records data of 300 adult patients with locally advanced/unresectable EC/GEJC who initiated dCRT (index date) within The US Oncology Network between 1 January 2015 and 30 June 2021. Patients were followed through 31 December 2022, last patient record or death, whichever occurred first. Descriptive analyses were conducted to evaluate patient and treatment characteristics. Kaplan-Meier methods were used to assess overall survival (OS) and real-world event-free survival (EFS) from index date. Results: Median age at index was 73 years; three-fourths of patients were male (74.3%), and three-fourths were Caucasian (73.7%). Stage III was the most common stage at initial diagnosis, followed by stage II and stage IVA (55.7%, 34.7%, and 5.3% respectively). The majority of the initial tumor location at diagnosis was esophageal (70.7%) whereas 29.3% were GEJ. Most patients had a baseline ECOG score of 0-1 (63.3%). Median (IQR) follow-up time to death or censor was 10.5 (4.0, 21.0) months from index. The most common initial regimen received was carboplatin+paclitaxel (87%), followed by cisplatin+fluorouracil (9%). Almost all patients received chemoradiotherapy concurrently (99.7%). Median radiation dose was 5040 cGy. Median duration of index treatment was 1.4 months. One-fifth of patients went on to receive a second treatment (21.7%). One-half of patients died before the end of the study observation period (53.7%), and 66% of patients experienced a clinical event (progression, locoregional recurrence, metastatic recurrence or death). Median (95% CI) OS and EFS were 18.1 (13.3, 21.8) and 8.9 (7.7, 10.6) months, respectively. Conclusions: Our study showed that patients mostly received carboplatin+paclitaxel as chemotherapy and did not receive further lines of treatments. Over 60% of patients experienced disease progression with a median survival of a year and a half. These clinical outcomes are poor for early esophageal cancer and support the development of more effective therapies to improve outcomes.

FS-1502 in patients with HER2 high expression, locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma: An open-label, multicenter, phase II study.

e15000 Background: FS-1502 is an antibody-drug conjugate composed of an anti-HER2 antibody, linker, and Monomethylauristatin F. In this study, we conducted an open-label, multicenter, two-cohort phase II trial to evaluate the efficacy and safety of FS-1502 in HER2- positive locally advanced or metastatic gastric or gastroesophageal junction cancer. Methods: Pts with HER2-positive (IHC 3+ or 2+/FISH+) who had received ≥1 prior treatment regimens were eligible and received FS-1502 2.3 mg/kg alone every 3 weeks. The study consists of Cohort 1 for pts received ≥2 lines of previous therapy and Cohort 2 for pts only received first-line of previous therapy, respectively. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression free survival (PFS), overall survival (OS), duration of response, disease control rate, and safety. Results: At data cutoff (Dec 24,2023), 46 pts were enrolled (intent-to-treat [ITT]), 35 pts were confirmed HER2-positive (IHC 3+ or IHC 2+/ISH+, Efficacy Evaluable Set [ES]) by central laboratory. In the ES, the median age was 58.3 years, 48.6% were IHC3+ and primary tumor location in 77.1% of pts was GC. 45.7% (16/35) pts had assigned to cohort 1 and 54.3% (19/35) pts had assigned to cohort 2. In cohort 1, median study follow-up time was 10.1 months, the investigator-assessed ORR was 37.5% (95% CI, 15.2-64.6), median PFS and OS were 4.3 months (95% CI, 1.5-5.8 months) and 10.0 months (95% CI,5.1-NA months), respectively. In cohort 2, median study follow-up time was 12.5 months, the investigator-assessed ORR was 52.6% (95% CI, 28.9-75.6). PFS and OS were 4.4 months (95% CI, 3.0-7.3 months) and 14.6 months (95% CI, 8.7-NA months), respectively. Grade≥3 treatment-related TEAEs were reported in 12 (26.1%) pts, ≥5% were hypokalemia (6.5%) and fatigue(6.5%). No adverse events leading to drug discontinuation or death. Efficacy and safety data are shown in table. Conclusions: FS-1502 showed promising activity with tolerable and manageable safety profile, which warrants further development in HER2-postive, advanced gastric or gastroesophageal junction adenocarcinoma who had received ≥1 prior treatment regimens. [Table: see text]

Interpectoral nodal dissection for invasive breast cancer: A retrospective single institution study from India.

e12585 Background: Interpectoral lymph nodes are one of the axillary lymphatic drainage sites in breast carcinoma. Usually dissection of Interpectoral nodes (IPN) avoided during axillary dissection as they are not the primary lymphatic drainage site. Our study aims to identify the rate of positivity of Interpectoral nodes in invasive breast cancer, predictors of IPN positivity in relation to tumour location, size, grade and hormone receptor status and to evaluate the need for IPN clearance during axillary dissection. Methods: A retrospective analysis of histopathology reports of 367 patients who underwent Axillary dissection in a single centre from Jan 2017-Dec 2022 for breast cancer was analysed. Inclusion criteria: Female Patients with operable Invasive Breast cancer with node positive axilla who underwent axillary dissection (upfront and post chemotherapy). Exclusion criteria: metastatic breast cancer, node-negative patients/sentinel lymph node biopsy, inadequate nodal dissection, and incomplete clinicopathological information. Data was analysed looking for presence of nodes in interpectoral tissue in Axillary dissection and to identify the positivity of interpectoral lymph nodes in specimens. Results: Interpectoral nodal dissection was done in n=216 of the 367 patients. The clinicopathological characters are described in Table. IPN were identified in 35% (n=77) of the 216 Axillary dissection specimens. IPN were positive in 7.8% (17 of 216) of patients who had interpectoral nodal dissection. 22% of the interpectoral lymph nodes removed were positive. As regards tumour size, Rotter's nodes were identified commonly in T3 and T4 tumours and positive in people with N2 and N3 disease. By multivariate analysis, T stage and N stage were the most important determinants of IPN yield and positivity. Site of tumour, neoadjuvant therapy, molecular subtype or Ki 67 were not found to be associated with either presence or positivity of interpectoral nodes. In 5 cases IPN positivity upstaged the nodal stage and in 1 patient it was the only positive node. Conclusions: As IPN is positive in most LABC, whenever axillary dissection is done in such cases Interpectoral nodes can be safely removed while dissecting level III nodes. Nodal recurrence is the most common site of recurrence post mastectomy and hence Interpectoral nodes need to be routinely removed in patients undergoing Axillary dissection for operable breast cancer to enable accurate staging and to prevent local or systemic failure. [Table: see text]

Deciphering pediatric low-grade glioma trajectories: Deep learning–based volumetrics for patients under surveillance.

2066 Background: Pediatric low-grade gliomas (pLGGs) have heterogeneous clinical presentations and prognoses. Given the morbidity of treatment, some suspected pLGGs, especially those found incidentally, are surveilled without treatment, though the natural histories of these tumors have yet to be systematically studied. We leveraged deep learning and multi-institutional data to methodically analyze longitudinal volumetric trajectories of pLGGs on surveillance, yielding insights into their growth trajectories and clinical implications. Methods: We conducted a pooled, retrospective study of pLGG patients diagnosed between 1992 and 2020 from two sources (Dana-Farber Cancer Institute/Boston Children’s Hospital and the Children's Brain Tumor Network), who were surveilled untreated for at least one-year post-diagnosis and who had linked clinical data and longitudinal MRI available. We applied a validated pLGG deep learning segmentation algorithm to longitudinal T2-weighted MRIs and calculated the 3-dimensional volumes at each timepoint. We evaluated individual tumor trajectories, curve shape, treatment initiation, and risk factors such as age, sex or tumor location for radiographic progression and regression (defined as volumetric change &gt;=25% and &lt;=-25% respectively) with univariable and multivariable logistic regression. Unsupervised time-series K-means and density-based spatial clustering with dynamic time wrapping were conducted to uncover volumetric phenotypes and a hybrid statistical time-series algorithm combining auto-regressive integrated moving average and generalized autoregressive conditional heteroskedasticity was evaluated to predict future volumetric changes. Results: Of 1774 scans from 129 patients (median follow-up of 4.0 years and median age of 13.9 years), baseline tumor median volume was 5.8 cm3 (range: 0.01-108.1), with 33 cortical (25.5%), 21 brainstem (16.2%), and 21 (16.2%) cerebellar locations. At the last follow-up, 33.8% of tumors progressed, 35.8% were stable, and 30.2% had regressed. Treatment was initiated for 46.5% of the tumors, of which 70.4% underwent surgery. Risk factors such as adolescent age, larger baseline volume size, cortical location and symptomatic presentation were most associated with progression ( p&lt;0.05 for each). Clustering revealed three distinct volumetric phenotypes with diverging natural histories, corresponding to progression, stability or regression. The hybrid forecasting showed average root-mean-squared error values of &gt;1 cm3 (std. &gt;0.18 cm3) at training and testing combined. Conclusions: Deep learning auto-segmentation enables longitudinal, volumetric tracking of pLGG, yielding novel insights into the clinical trajectories of untreated tumors on surveillance, allowing a classification into progressors, regressors and stables.