Regional Metastases Research Articles

Phase II trial of terelizumab combined with radiotherapy of locally advanced unresectable esophageal squamous cell carcinoma: TREC trial.

e16086 Background: Concurrent chemoradiotherapy (CCRT) is the standard therapy for locally advanced unresectable esophageal squamous cell cancer (ESCC)，However, some patients cannot tolerate or are unwilling to CCRT. The aim of this phase II trial was to assess the efficacy and safety of the tirelizumab combined with radiotherapy in patients of locally advanced unresectable ESCC. Methods: Key eligibility criteria were as follows: ESCC of clinical stage Ⅱ-Ⅳa; aged 18 to 90 years; cannot tolerate or are unwilling to CCRT; ECOG performance status 0 or 1; and performed radiotherapy: Involvement field irradiation, nodal GTV (GTVn) (regional lymphatic metastasis) radiotherapy dose 60Gy, the esophageal gross tumor volume (GTVt) radiotherapy dose 50Gy, if the gastroscope pathology is completely relieved, otherwise it is 60Gy. All patients registered before radiotherapy. The patient received concurrent therapy with tirelizumab (200mg every time, 3-week cycle), until the disease progresses or clinical benefits are lost (the longest time is 12 months). The primary endpoint was the esophageal gross tumor pathological complete remission rate (pCR). Results: Between 01 August 2021 and 31 December 2022, 31 patients were enrolled, and 27 completed radiotherapy and at least two times of tirelizumab treatment. Data cutoff date was 31 January 2023, median follow-up time among survivors after radiotherapy was 9 months (range 4-20). The esophageal gross tumor pCR rate was 66.7% (95% CI, 14.3%-52.3%) and treatment-related adverse events (TRAEs) of low severity (grade 1-2, 48.1%; grade 3, 7.4%; grade 4-5, no). No treatment-related mortality occurred. Two (7.4%) patients had tumor recurrence and two (7.4%) patients died (Infection and heart disease). The 1-year PFS rate, median PFS and median OS had not been reached yet. For locally advanced unresectable ESCC that can't receive CCRT, the combination of tirelizumab and radiotherapy shows promising efficacy and acceptable toxicity, providing a feasible and effective choice. The research of long-term survival analysis is under way. Conclusions: Concurrent radiotherapy with tirelizumab shows promising efficacy and controllable safety for patients with locally advanced ESCC who are unable or unwilling to undergo CCRT, and warrants further evaluation in larger studies. Clinical trial information: ChiCTR2100053182 .

A phase II trial of neoadjuvant nivolumab, docetaxel, and cisplatin therapy followed by surgery and radiation therapy for resectable high-grade salivary gland carcinoma.

TPS6110 Background: Salivary gland carcinomas (SGCs) are rare entities that contribute to approximately 5% of head and neck malignancies. The current standard therapy for resectable SGC is complete surgical resection with adjuvant radiotherapy or chemoradiotherapy. However, the patients with high-grade histological subgroup tumors have the highest risk of regional and distant metastasis as the primary cause of treatment failure.. The previous evidence demonstrates that neoadjuvant chemotherapy showed a statistically significant advantage in survival for patients with head and neck cancer. Based on the success of neoadjuvant immune checkpoint inhibitors (ICI) in preventing disease recurrence and achieving pathologic complete response (pCR) in different types of cancer, we designed this study by incorporating nivolumab combined with neoadjuvant cytotoxic chemotherapy in patients with potentially resectable high-grade SGCs. Methods: This study is the phase II, open-label, single-center study of nivolumab in combination with docetaxel, and cisplatin as a neoadjuvant therapy in high-grade resectable SGCs. All the patients must be confirmed with pre-defined high-grade histology and clinically node-positive. As the representative inclusion/exclusion criteria, all the patients must not receive prior cancer therapy in advance to study enrollment, including another kind of immunotherapy, cytotoxic chemotherapy, or radiotherapy. Three cycles of nivolumab (360mg), docetaxel (60mg per m2), and cisplatin (60mg per m2) are applied every three weeks. Three weeks after the last treatment, the patient is re-evaluated for the surgery and will undergo surgery within seven weeks after the last treatment. Based on the surgical pathologic outcome, additional radiotherapy will be initiated between 4 to 8 weeks after the surgery per the following guidance; R0: 59.4Gy/25fx; R1 or R2: 59.4Gy/25fx with optional boost 6.6Gy/3fx. The primary objective is the major pathologic response rate defined by ≤ 10% of tumors composed of viable tumors. Complete resection rate, response rate, downstaging at pathologic staging, two-year distant metastasis free-survival, disease-free survival, overall survival, safety results, surgical outcomes of facial nerve function, completeness of post-neoadjuvant surgery will be analyzed as the secondary objectives. The sample size was calculated using H0 of mPR ≤25% and H1 of mPR ≥50%, according to the one-arm binomial model (power of 90% and one-sided alpha of 0.05). A total of 50 patients will be recruited, include 40 evaluable patients. This study is currently recruiting patients at Samsung Medical Center, South Korea. The first subject received treatment in Nov. 2022 and three patients received the treatment. The time point for the primary analyses is Q3.2025. (ONO-4538-X78). Clinical trial information: NCT05727410 .

Primary Cutaneous Mucinous Eccrine Carcinoma Arising in the Lower Eyelid: A Rare Case Report

Mucinous Eccrine carcinoma (MEC) is a rare malignant tumor related to the eccrine sweat gland and is commonly located on the face, especially around the eyelids and scalp. Most of these tumors are diagnosed at age 40’s to 60’s and exhibit a wide variety of patterns in addition to the general appearance previously reported. MEC is difficult to diagnose clinically, but can be diagnosed by accompanying biopsy.We present the case of a 75-year-old man who complained of a gradually growing Left lower lid tumor of duration one year. Initially, the tumor was mistaken for an epidermal cyst and treated by surgical resection.However, biopsy findings resulted in a diagnosis of Mucinous Eccrine carcinoma. Therefore, we performed wide excision and flap reconstruction surgery. In a one year follow-up examination, the patient achieved successful functional and aesthetic results without regional or distant metastasis and recurrence.

The incidence of periocular melanoma: An epidemiologic study in Olmsted County, Minnesota

To the Editor: Melanoma arising in the periocular area presents a unique treatment challenge due to anatomic and functional constraints. To date, most information regarding periocular melanoma is gleaned from extrapolated data from other sites of the body, assuming similar biologic behavior. We aimed to identify the overall incidence, pathologic features, and surgical outcomes of periocular melanoma. Following Institutional Review Board (IRB) approval, using the Rochester Epidemiology Project (a multicenter medical records–linkage system encompassing the Olmsted County population), we identified patients with a first lifetime diagnosis of periocular melanoma between January 1, 1970, and December 31, 2020, while a local resident of Olmsted County, Minnesota. Outside (nonresident) referral cases were excluded. Periocular melanoma was defined as a melanoma arising within the orbital rim – on the upper or lower eyelid, lateral canthus, or eyebrow. A total of 10 patients with primary periocular melanoma were identified. The overall incidence rate of periocular melanoma was 0.2686 per 100,000 patient-years. Among all melanomas diagnosed during that timeframe in Olmsted County, 0.43% were periocular in location. No cases extended onto conjunctiva. The histogenic subtype was lentigo maligna in 8 (80.0%). There was 1 superficial spreading melanoma and 1 case without documentation of histogenic subtype. Incidence of in situ (50.0%) and invasive (50.0%) melanomas was equal. Among invasive melanomas, the average Breslow depth was 0.90 mm (range, 0.2-2.6 mm). Seven (70.0%) were treated with Mohs micrographic surgery (MMS). One (10%) was treated with wide local excision. The 2 cases that did not undergo further surgical treatment were both diagnosed prior to 2000 and were removed entirely via initial excisional biopsy. There was 1 regional metastasis to the parotid gland and lymph node, 2.5 years after diagnosis of a superficial spreading melanoma, Breslow 0.7 mm, status-post treatment with MMS. There were no other local or distant recurrences. There were no melanoma-specific deaths. Mean follow-up time was 7.4 years (range 3.1-13.2). This study demonstrates the relative rarity of periocular melanoma, comprising only 0.43% of all melanomas. Comparatively, basal cell carcinoma (BCC) occurs on the eyelid 16% of the time.1Salomon J. Bieniek A. Baran E. Szepietowski J.C. Basal cell carcinoma on the eyelids: own experience.Dermatol Surg. 2004; 30: 257-263PubMed Google Scholar Our study found an overall periocular melanoma incidence rate of 0.2686 per 100,000 patient-years. A previous Olmsted County cohort reported an incidence of eyelid BCC as 14.35 per 10,000 individuals per year, and an incidence of eyelid SCC as 1.37 cases per 100,000 individuals per year.2Cook Jr., B.E. Bartley G.B. Epidemiologic characteristics and clinical course of patients with malignant eyelid tumors in an incidence cohort in Olmsted County, Minnesota.Ophthalmology. 1999; 106: 746-750Abstract Full Text Full Text PDF PubMed Google Scholar The behavior of melanoma seems to parallel primary cutaneous melanoma of head and neck sites. Most tumors were associated with chronic sun exposure; 80% of cases were lentigo maligna subtype. There was 1 regional recurrence in our study, no distant recurrences, and no deaths due to melanoma. The most significant advantage of our study is in its epidemiologic design. The limitations of this study include the retrospective nature of our analysis and the homogenous demographics of Olmsted County, comprised of mostly Caucasian individuals of higher socioeconomic status.3St Sauver J.L. Grossardt B.R. Leibson C.L. Yawn B.P. Melton 3rd, L.J. Rocca W.A. Generalizability of epidemiological findings and public health decisions: an illustration from the Rochester Epidemiology Project.Mayo Clin Proc. 2012; 87: 151-160Abstract Full Text Full Text PDF PubMed Scopus (487) Google Scholar Additionally, some melanomas may have been missed if the tumor was initially labeled as another anatomic site (cheek, nose, temple, etc.) and had extension onto the lid proper. None disclosed. We would like to acknowledge Austin Todd, MS, for his assistance in statistical analysis.

One-stage reconstruction using a fibula osteocutaneous free flap and an anterolateral thigh free flap for an extensive composite defect after en bloc resection of squamous cell carcinoma on the mouth floor, mandible, and anterior neck: A CARE-compliant case report.

Although regional metastasis to the lymph nodes is common in advanced oral cancer, extensive local invasion into surrounding structures such as the mandible, skin and soft tissue of the neck, and masticator space is relatively rare. Sometimes surgical treatment cannot be performed and only palliative chemotherapy and radiation therapy are offered to preserve the quality of life of patients with advanced oral cancer. Nevertheless, the surgical resection of tumors remains the most effective treatment. This study presents a case of aggressive mouth floor cancer in which extensive composite defects on the mouth floor, oral mucosa, mandible, skin and soft tissue of the neck caused by tumor resection were reconstructed. A 66-year-old man and a 65-year-old man with no significant personal or family history visited our clinic due to a large and multiple masses on the floor of the mouth and both sides of the neck. Histopathological evaluation of the biopsy specimen revealed squamous cell carcinoma. A fibula osteocutaneous free flap and customized titanium plate were used for the intraoral lining. Mandibular reconstruction was performed using a 3D-printed bone model, and an anterolateral thigh free flap was used to resurface the anterior of the neck. Reconstruction using this method was successful, and excellent functional and aesthetic outcomes were achieved without cancer recurrence. This study show that the reconstruction of extensive composite defects of the oral mucosa, mandible, and neck soft tissue following surgical resection of mouth floor cancer can be performed in a single-stage operation. Through a single-stage reconstruction, both excellent functional aspects without cancer recurrence and satisfactory aesthetic outcomes can be obtained.

Diagnosis and treatment of primary urethral melanoma with regional lymphatic metastasis in an elderly woman: a case report and review of available therapies

BackgroundMucosal melanomas account for 17% of melanomas, and less than 1% affect the urogenital tract. Primary urethral melanoma is extremely rare; less than 200 cases have been reported so far since it was first described. The clinical presentation is usually delayed, and the prognosis is generally poor.Case presentation.An 86-year-old female was referred to urology due to the presence of a three-month-old violaceous mass in the urethral meatus protruding through the vagina. On physical examination, a pedunculated, hyperpigmented, friable, and tender lesion was seen in the urethral meatus bulging between the labia minora. After initial diagnostic studies, the patient was taken to surgical resection of the lesion. The pathology report identified the lesion as a malignant melanoma of the urethra, and staging studies revealed regional lymph node metastases. After discussing the treatment options with the patient, palliative therapy with nivolumab was started. In follow-up at 26 months, the patient had evidence of extensive lymph node involvement, but a conserved performance status and no visceral metastases.ConclusionPrimary melanoma of the female urethra is an uncommon disease with a poor prognosis. Despite the deficiency in literature regarding its management, it is important to consider patient expectations and preferences when treating this rare disease.

Quality assurance and safety of hippocampal avoidance prophylactic cranial irradiation in the multicenter randomized phase III trial (NCT01780675)

ObjectiveNCT01780675, a multicenter randomized phase III trial of prophylactic cranial irradiation (PCI) versus PCI with hippocampal sparing in small cell lung cancer (SCLC) investigated neurocognitive decline and safety. As part of quality assurance, we evaluated if hippocampal avoidance (HA)-PCI was performed according to the NCT01780675 trial protocol instructions, and performed a safety analysis to study the incidence and location of brain metastases for patients treated with HA-PCI. MethodsThis retrospective analysis evaluated the quality of the irradiation given in the randomized controlled trial (RCT) comparing SCLC patients receiving PCI with or without hippocampal avoidance, using intensity modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT). The dose distribution for each patient receiving HA-PCI was retrieved and analyzed to evaluate if the treatment dose constraints were met. A questionnaire was sent out to all participating sites, and data on radiotherapy technique, pre-treatment dummy runs, phantom measurements and treatment electronic portal imaging device (EPID) dosimetry were collected and analyzed. As part of the safety analysis, the follow-up magnetic resonance imaging (MRI) or computerized tomography (CT) scans on which cranial disease progression was first diagnosed were collected and matched to the radiotherapy planning dose distribution. The matched scans were reviewed to analyze the location of the brain metastases in relation to the prescribed dose. ResultsA total of 168 patients were randomized in the NCT01780675 trial in 10 centers in the Netherlands and Belgium from April 2013 until March 2018. Eighty two patients receiving HA-PCI without evidence of brain metastases were analyzed. All patients were treated with 25 Gy in 10 fractions. Dummy runs and phantom measurements were performed in all institutions prior to enrolling patients into the study. The radiotherapy (RT) plans showed a median mean bilateral hippocampal dose of 8.0 Gy, range 5.4–11.4 (constraint ≤ 8.5 Gy). In six patients (7.3%) there was a protocol violation of the mean dose in one or both hippocampi. In four of these six patients (4.9%) the mean dose to both hippocampi exceeded the constraint, in 1 patient (1.2%) only the left and in 1 patient (1.2%) only the right hippocampal mean dose was violated (average median dose left and right 8.9 Gy). All patients met the trial dose constraint of V115%PTV ≤ 1%; however the DmaxPTV constraint of ≤ 28.75 Gy was violated in 22.0% of the patients. The safety analysis showed that 14 patients (17.1%) developed cranial progression. No solitary brain metastases in the underdosed region were found. Two out of 11 patients with multiple brain metastasis developed metastasis in the underdosed region(s). ConclusionsThe radiotherapy quality within the HA-PCI trial is performed according to the protocol guidelines. The dose constraints to the hippocampi are met in the vast majority of cases. In all patients, the volume of the brain for which a higher dose was accepted, is according to the trial. However, within this volume there are small areas with higher doses than advised.

Insurance-Based Disparities in Guideline-Concordant Thyroid Cancer Care in the Era of De-escalation

IntroductionPrior studies have demonstrated insurance-based disparities in the treatment of well-differentiated thyroid cancer. However, it remains unclear whether these disparities have persisted in the era of the 2015 American Thyroid Association (ATA) management guidelines. The goal of this study was to assess whether insurance type is associated with the receipt of guideline-concordant and timely thyroid cancer treatment in a modern cohort. MethodsPatients diagnosed with well-differentiated thyroid cancer between 2016 and 2019 were identified from the National Cancer Database. Appropriateness of surgical and radioactive iodine treatment (RAI) was determined based on the 2015 ATA guidelines. Multivariable logistic regression and Cox proportional hazard regression analyses, stratified at age 65, were used to evaluate the associations between insurance type and appropriateness and timeliness of the treatment. Results125,827 patients were included (private = 71%, Medicare = 19%, Medicaid = 10%). Compared to privately insured patients, patients with Medicaid more frequently presented with tumors >4 cm in size (11% versus 8%, P < 0.001) and regional metastases (29% versus 27%, P < 0.001). However, patients with Medicaid were also less likely to undergo appropriate surgical treatment (odds ratio 0.69, P < 0.001), less likely to undergo surgery within 90 d of diagnosis (hazard ratio 0.80, P < 0.001), and more likely to be undertreated with RAI (odds ratio 1.29, P < 0.001). There were no differences in the likelihood of guideline-concordant surgical or medical treatment by insurance type in patients ≥65 y old. ConclusionsIn the era of the 2015 ATA guidelines, patients with Medicaid remain less likely to receive guideline-concordant, timely surgery and more likely to be undertreated with RAI compared to privately insured patients.

Resident memory T cells in the lymph node balance localized and systemic protection

Abstract The endogenous mechanisms that protect against pathogen infection in the lymph node (LN) and LN metastasis during early tumor development remain poorly understood. Resident memory T cells (Trm), which do not circulate, provide highly localized protection to both pathogens and cancer, and correlate with better clinical outcomes. Here we track LN Trm development using models of cutaneous viral infection to determine the kinetics and requirements for their differentiation. We show that after viral skin infection, Trm form in the draining LN concurrent with their establishment at the initial site of infection in skin. LN Trm formed specifically in LNs draining infected skin expressing cognate antigen and did not form in contralateral controls. These data supported a hypothesis that T cell egress out of infected skin through lymphatic vessels was necessary for LN Trm formation. Consistent with this hypothesis, LN Trm were absent from mice lacking dermal lymphatic vessels indicating that either fluid transport or cellular transport from the skin to the LN was necessary for the establishment of LN Trm. To decouple LN priming from T cell egress we resected infected skin days 5 and 20 post infection. Ear resection at 5 days post infection impaired Trm formation but circulating memory T cell responses were unaffected. We demonstrated that LN Trm are poised for cell killing as evidenced by constitutive expression of granzymes, and were able to protect against viral rechallenge. These findings indicate that LN Trm are poised to provide rapid, localized protection specific to the draining LN. These data may suggest that LN’s harbor populations capable of controlling regional cancer metastasis and pathogenic infections. Supported by grants from NIH (R01CA238163)

Clinical management of mammary carcinoma in dogs: Current scenario

Mammary carcinoma is one of the most common skin tumors of mammary gland area in canine. Fifty cases of mammary carcinoma were reported during the period of study at Teaching Veterinary Clinical Complex and Department of Veterinary Surgery and Radiology. Eighty animals were screened for selecting fifty mammary carcinoma and these are the subjects of present study population. The prevalence of tumors across the age groups were highest among 8 to 12 years, followed by 12 years and least in dogs below 8 years. Breed wise predisposition was highest among Labrador (36.67%), followed by Spitz and German shepherd (20% each), Mongrel (10%), Dachshund (6.67%), Rottweiler and beagle (3.33% each). More cases of mammary carcinoma were malignant (70%) with metastasis to regional lymph node a common finding. Malignancy criteria were size, hardness, of the tumor and metastasis to regional lymphocenter. Axillary lymph node for 1st, 2nd mammary gland tumor and inguinal, medial iliac lymph node for 2nd, 3rd, and 4th mammary gland were common site of regional metastasis. Most of the patient had clinical stage III tumor (30%) followed by stage II (23.33%). Three cases of stage IV mammary carcinoma were recorded in which three view thoracic radiography showed nodular opacities of the thorax and confirmed as positive sign of metastasis. Histopathologically, solid mammary carcinoma, fibroadenoma, adenocarcinoma were common types of carcinomas. Malignant mammary tumor dogs had significantly (p

Repeated Surgery in a Case of Epithelial-Myoepithelial Carcinoma of the Parotid Gland that was Difficult to Distinguish from Pleomorphic Adenoma.

Epithelial-myoepithelial carcinoma (EMC) of the parotid gland is a comparatively rare tumor that accounts for less than 1% of all salivary gland tumors. A patient with EMC of the parotid gland that was initially diagnosed as pleomorphic adenoma and that recurred locally during the watchful waiting period but was controlled by surgery under local anesthesia is reported. An 80-year-old man had noticed a swelling in the left infra aural region. A left parotid gland tumor was suspected, and he was referred to our department. Magnetic resonance imaging (MRI) and fine-needle aspiration cytology findings were suggestive of pleomorphic adenoma of the superficial lobe of the parotid gland, and this was therefore resected under general anesthesia. Postoperative histopathological examination, immunostaining, and genetic tests resulted in a diagnosis of EMC. Postoperative pathological review showed that part of the resection margin was positive. The possibility of recurrence was explained to the patient, and additional treatment was recommended, but since the patient did not desire this, a policy of watchful waiting was adopted. Signs of cutaneous metastasis in the left infra aural region were detected at 13 months postoperatively, and this metastasis was excised under local anesthesia. The resection margin was negative, and the patient's course remains uneventful. EMC is classified as a low-grade malignant tumor, but it requires stringent monitoring because of its frequent local recurrence. Since local control can usually be achieved by surgical treatment alone, and postoperative adjuvant therapy may not necessarily warranted.

Clinical Characteristics, Treatment, and Outcomes of Peritoneal Strumosis: A Report of Three Cases and Systematic Review.

Benign struma ovarii (SO) has a probability of metastasis named "peritoneal strumosis", which is extremely rare, such that the specific clinical characteristics, treatment options, and survival outcomes remain unclear. We screened three cases of peritoneal strumosis among 229 cases of SO treated in our hospital. Case 1 was a 36-year-old woman with extensive peritoneal seedings at initial presentation. The second one was a 49-year-old with trocar site implant 11 years after laparoscopic adnexectomy. Case 3 was a 45-year-old woman who had an isolated lesion at the anterior surface of the rectum after laparoscopic ovarian cystectomy for SO 14 years ago. These three patients underwent surgery without any adjuvant treatment and remained disease-free after 30 to 68 months. A systematic review was then conducted and another 16 cases were identified. More than half (10/19, 52.6%) of the patients had previous SO-related ovarian surgery. The median interval between prior SO-related surgery and the initial presentation of peritoneal strumosis was 10.0 years; both regional and distant metastasis, even in the liver, lung, and heart, could also be affected. Surgery was the mainstay therapy (18/19, 94.7%), in which six patients (6/19, 31.7%) were treated with total thyroidectomy (TT) followed by radioiodine (RAI) therapy. Postoperative chemotherapy was only applied in one patient, and the last one only received a diagnostic biopsy without further treatment. Recurrence was noted in two patients with a median recurrence-free survival of 12 years, where surgical excision and RAI were then performed. No death occurred after a mean follow-up of 53 months, where 12 patients achieved no evidence of disease and five were alive with the disease. Peritoneal strumosis has unpredictable biological behaviors and the crude incidence is approximately 1.3% in SO. Patients with peritoneal strumosis have excellent survival outcomes, irrespective of different treatment strategies employed. Surgery with personalized RAI should be preferred and long-term close monitoring is recommended.

Microphysiological head and neck cancer model identifies novel role of lymphatically secreted monocyte migration inhibitory factor in cancer cell migration and metabolism

Regional metastasis of head and neck cancer (HNC) is prevalent (approximately 50% of patients at diagnosis), yet the underlying drivers and mechanisms of lymphatic spread remain unclear. The complex tumor microenvironment (TME) of HNC plays a crucial role in disease maintenance and progression; however, the contribution of the lymphatics remains underexplored. We created a primary patient cell derived microphysiological system that incorporates cancer-associated-fibroblasts from patients with HNC alongside a HNC tumor spheroid and a lymphatic microvessel to create an in vitro TME platform to investigate metastasis. Screening of soluble factor signaling identified novel secretion of macrophage migration inhibitory factor (MIF) by lymphatic endothelial cells conditioned in the TME. Importantly, we also observed patient-to-patient heterogeneity in cancer cell migration similar to the heterogeneity observed in clinical disease. Optical metabolic imaging at the single cell level identified a distinct metabolic profile of migratory versus non-migratory HNC cells in a microenvironment dependent manner. Additionally, we report a unique role of MIF in increasing HNC reliance on glycolysis over oxidative phosphorylation. This multicellular, microfluidic platform expands the tools available to explore HNC biology in vitro through multiple orthogonal outputs and establishes a system with enough resolution to visualize and quantify patient-to-patient heterogeneity.

Proteomic profiling of cutaneous melanoma explains the aggressiveness of distant organ metastasis.

Despite recent developments in managing metastatic melanomas, patients' overall survival remains low. Therefore, the current study aims to understand better the proteome-wide changes associated with melanoma metastasis that will assist with identifying targeted therapies. The latest development in mass spectrometry-based proteomics, together with extensive bioinformatics analysis, was used to investigate the molecular changes in 60 formalin-fixed and paraffin-embedded samples of primary and lymph nodes (LN) and distant organ metastatic melanomas. A total of 4631 proteins were identified, of which 72 and 453 were significantly changed between the LN and distant organ metastatic melanomas compared to the primary lesions (adj. p-value <0.05). An increase in proteins such as SLC9A3R1, CD20 and GRB2 and a decrease in CST6, SERPINB5 and ARG1 were associated with regional LN metastasis. By contrast, increased metastatic activities in distant organ metastatic melanomas were related to higher levels of CEACAM1, MC1R, AKT1 and MMP3-9 and decreased levels of CDKN2A, SDC1 and SDC4 proteins. Furthermore, machine learning analysis classified the lesions with up to 92% accuracy based on their metastatic status. The findings from this study provide up to date proteome-level information about the progression of melanomas to regional LN and distant organs, leading to the identification of protein signatures with potential for clinical translation.

Cribriform adenocarcinoma of the minor salivary glands: a case report

BackgroundPolymorphous adenocarcinoma is the third most common malignant salivary gland tumor. Within polymorphous adenocarcinoma, cribriform adenocarcinoma of salivary glands is a rare subtype and resembles papillary thyroid carcinoma histopathologically. Diagnostically, cribriform adenocarcinoma of salivary glands is challenging for pathologists and surgeons alike as initial presentation and cytologic nuclear features can be easily confused with papillary thyroid carcinoma arising from a thyroglossal duct remnant or lingual thyroid.Case presentationA healthy 64-year-old Caucasian woman presented to a community otolaryngologist with a 4-year history of progressive postnasal drip, globus sensation, and eventual dysphonia. Flexible fiberoptic laryngoscopy showed a large, smooth, vallecular lesion filling the oropharynx. Computed tomography imaging of the neck showed a rounded heterogeneous mass centered within the right aspect of the oropharynx measuring 4.2 × 4.4 × 4.5 cm. Fine needle aspiration biopsy was suspicious for papillary carcinoma due to microscopic findings of malignant cells, nuclear grooves, and a powdery chromatin pattern. In the operating room, the tumor was resected en bloc using a lateral pharyngotomy approach with partial resection of the right lateral hyoid. A limited cervical lymphadenectomy was performed to facilitate the lateral pharyngotomy approach and two out of three lymph nodes demonstrated regional metastatic disease. Nuclear grooves, nuclear membrane notching, and occasional intranuclear pseudoinclusions were identified, which are overlapping histopathological characteristics of papillary thyroid carcinoma and cribriform adenocarcinoma of salivary glands. It was negative for thyroglobulin and thyroid transcription factor-1, which was in keeping with cribriform adenocarcinoma of salivary glands rather than papillary thyroid carcinoma.ConclusionIt is difficult to distinguish cribriform adenocarcinoma of salivary glands from papillary thyroid carcinoma solely by cytology, and the distinct characteristics of regional lymph node metastasis coupled with nuanced histologic differences should be emphasized in the evaluation of patients presenting with neck lymphadenopathy and an unknown primary or tongue mass. If sufficient fine needle aspiration biopsy material is available, thyroid transcription factor-1, thyroglobulin, or molecular testing may prove useful in differentiating cribriform adenocarcinoma of salivary glands from papillary thyroid carcinoma. A misdiagnosis of papillary thyroid carcinoma may lead to inappropriate treatment including unnecessary thyroidectomy. Therefore, it is critical for both pathologists and surgeons to be aware of this uncommon entity to avoid misdiagnosis and subsequent mismanagement.

Physiologic 18F-FDG muscle uptake in severe COPD: Implications for accurate lung cancer staging.

Recognizing physiologic 18F-fluorodeoxyglucose (FDG) uptake in severe COPD is crucial to avoid mistaking it for lung cancer metastasis. Correlating 18F-FDG avid lesions with co-registered computed tomography is essential for accurate lung cancer staging and preventing unnecessary interventions.

Value of clinical features combined with multimodal ultrasound in predicting lymph node metastasis in cervical central area of papillary thyroid carcinoma.

To explore the clinical features, multimodal ultrasound features and multimodal ultrasound imaging features in predicting lymph node metastasis in the central cervical region of papillary thyroid carcinoma. A total of 129 patients with papillary thyroid carcinoma (PTC) confirmed by pathology were selected from our hospital from September 2020 to December 2022. According to the pathological results of cervical central lymph nodes, these patients were divided into metastatic group and non-metastatic group. Patients were randomly sampled and divided into training group (n = 90) and verification group (n = 39) according to the ratio of 7:3. The independent risk factors for central lymph node metastasis (CLNM) were determined by least absolute shrinkage and selection operator and multivariate logistic regression. Based on independent risk factors to build a prediction model, select the best diagnostic effectiveness of the prediction model sketch line chart, and finally, the line chart calibration and clinical benefits were evaluated. A total of 8, 11 and 17 features were selected from conventional ultrasound images, shear wave elastography (SWE) images and contrast-enhanced ultrasound (CEUS) images to construct the Radscore of conventional ultrasound, SWE and CEUS, respectively. After univariate and multivariate logistic regression analysis, male, multifocal, encapsulation, iso-high enhancement and multimodal ultrasound imaging score were independent risk factors for cervical CLNM in PTC patients (p < 0.05). Based on independent risk factors, a clinical combined with multimodal ultrasound feature model was constructed, and multimodal ultrasound Radscore were added to the clinical combined with multimodal ultrasound feature model to form a joint prediction model. In the training group, the diagnostic efficacy of combined model (AUC = 0.934) was better than that of clinical combined with multimodal ultrasound feature model (AUC = 0.841) and multimodal ultrasound radiomics model (AUC = 0.829). In training group and validation group, calibration curves show that the joint model has good predictive ability for cervical CLNM of PTC patients; The decision curve shows that most of the net benefits of the nematic chart are higher than those of clinical + multimodal ultrasound feature model and multimodal ultrasound radiomics model within a reasonable risk threshold range. Male, multifocal, capsular invasion and iso-high enhancement are independent risk factors of CLNM in PTC patients, and the clinical plus multimodal ultrasound model based on these four factors has good diagnostic efficiency. The joint prediction model after adding multimodal ultrasound Radscore to clinical and multimodal ultrasound features has the best diagnostic efficiency, high sensitivity and specificity, which is expected to provide objective basis for accurately formulating individualized treatment plans and evaluating prognosis.

Radiation osteitis: incidence and clinical impact in the setting of radiation treatment for soft tissue sarcoma.

Radiotherapy is an important component of soft tissue sarcoma management. Radiation osteitis is a common radiographic finding identified in the setting of radiotherapy on magnetic resonance imaging (MRI). This study aims to identify the incidence of radiation osteitis in patients who received radiotherapy for soft tissue sarcoma and if a further workup, including a biopsy, was performed for concerning MRI findings. Medical records of patients with soft tissue sarcoma who received radiotherapy from 2008 to 2020 were retrospectively reviewed. Patients with at least one MRI of the sarcoma site following radiotherapy and information regarding radiotherapy treatments were included. MRIs of these patients were reviewed for the presence of radiation osteitis by two musculoskeletal radiologists. The clinical course of these patients including biopsy for concerning MRI findings, local recurrence, and metastasis was recorded. Thirty soft tissue sarcoma patients who received radiation for soft tissue sarcoma were included. Radiation osteitis was present in 18 patients. The time to osteitis present on MRI following radiotherapy completion was a median of 4.5 months. Biopsy for concerning MRI findings was performed in eight patients, five for local recurrence, and three for regional osseous metastasis. Three patients had confirmed osseous metastases. Although radiation osteitis is often a benign imaging finding, it can be difficult to discern these lesions from potentially malignant sites of disease. We recommend multidisciplinary management of soft tissue sarcoma at sarcoma centers to appropriately identify benign from malignant lesions and decide the necessity of a biopsy.

Abstract 2216: Construction of a prognostic 6-gene signature for breast cancer based on multi-omics data

Abstract Breast cancer (BC) is a heterogeneous disease. Distinguishing BC patients with different prognosis can help to make clinical strategies. In our study, we tried to identify novel prognostic genetic biomarkers for BC by using multi-omics data and establish a risk score (RS) signature with genetic biomarkers which have high predictive value. A combined significance (pcombined) of each gene was calculated by Fisher’s method based on the p value of the difference examination of the respective index in RNA-seq, CNV, and DNA methylation data of corresponding genes from TCGA-BRCA dataset. Genes with a pcombined &amp;lt; 0.010 were subjected to univariate cox and Lasso regression to screen out hub genes, whereby a RS signature consisted of six genes, C15orf52, C1orf228, CEL, FUZ, PAK6, and SIRPG, was established. With the Kaplan-Meier (KM) method, the receiver operating characteristic curves (ROC), multivariate cox regression, Nomogram, and decision curve analysis (DCA), the predicted performance of the RS signature was assessed in TCGA-BRCA, GSE7390, and GSE20685. The predicted performance in TNBC patients was emphatically analyzed in TCGA-BRCA and GSE103091, while immune characteristics were also explored. Basing on the data from Genomics of Drug Sensitivity in Cancer (GDSC) database and related R package, we further examined the drug sensitivity of TNBC patients with different RS. With survival rates having significant differences in all KM analyses and most area under ROCs reaching 0.700, the RS signature could distinguish the prognosis of patients, even stratified by disease stages or subtypes. The RS also showed a stronger predictive ability than traditional clinical indicators, including age, tumor topology (T), regional lymph node (N), metastasis (M), and TNM stage. The down-regulated expressions of many immune checkpoints were observed in TNBC patients with higher RS, while the sensitivity of many antitumor drugs was reduced in those with higher RS, except for BI2536 (CAS No.: 755038-02-9), which demonstrated a smaller half maximal inhibitory concentration (which mean a higher drug sensitivity) in TNBC patients with higher RS. In conclusion, the six genes RS signature established based on multi-omics data exhibited well performance in predicting the prognosis of BC patients, regardless of disease stages or subtypes. Contributing to a more personalized treatment, the RS signature might benefit the outcome of BC patients. Citation Format: Zeyu Xing, Yuting Hong. Construction of a prognostic 6-gene signature for breast cancer based on multi-omics data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2216.

P165 Distance from epicenter of tumor to nipple in predicting regional lymphnode metastasis

P165 Distance from epicenter of tumor to nipple in predicting regional lymphnode metastasis