Extensive Local Invasion Research Articles

Paraganglioma With Intracranial Invasion Demonstrated on 68Ga-DOTATATE PET/CT.

68Ga-DOTATATE PET/CT demonstrates superior sensitivity compared with other cross-sectional and functional imaging techniques in detecting head and neck paragangliomas. It is the primary recommended imaging modality for the evaluation of head and neck paragangliomas, especially in patients suspected of having locally aggressive, multifocal, or metastatic disease, as well as those being considered for targeted peptide-receptor therapy. Herein, we demonstrate the 68Ga-DOTATATE PET/CT findings of a skull base paraganglioma with extensive local invasion and intracranial extension.

Primary Small Cell Carcinoma of Left Maxillary Sinus: A Case Report of Rare Tumor on Rare Location

Introduction: Primary extrapulmonary small cell carcinoma (EPSCC) is a rare and aggressive tumor with diverse clinical manifestations. In the realm of head and neck pathology, EPSCC most commonly presents in the larynx or oral cavity. Sinonasal small cell neuroendocrine carcinoma represents a particularly infrequent and aggressive neoplasm affecting the nasal cavity and paranasal sinuses. Case Presentation: Here in, we are presenting a case of a 40-year-old nonsmoking male with left maxillary sinus EPSCC, demonstrating extensive local invasion and regional lymphadenopathy. The patient presented with nasal obstruction, ocular swelling, visual loss, and multiple neck swellings. Diagnosis was challenging, requiring a multidisciplinary approach and histopathological confirmation. Immunohistochemistry revealed positive cytokeratin AE1/AE3 and synaptophysin markers validating the diagnosis of small cell carcinoma. Conclusion: This case underscores the diagnostic complexities and highlights the importance of swift intervention and a multidisciplinary treatment approach for optimizing patient outcomes in rare and aggressive tumors like EPSCC. Early detection and prompt management are crucial in resource-limited settings to mitigate morbidity and mortality.

12205 Challenging Case Of Anaplastic Thyroid Cancer With Unusual Histological Features: A Diagnostic Dilemma With High Grade Sarcoma

Abstract Disclosure: B. Gautam: None. B. Tiwari: None. M.S. Hossain: None. S. Hossain: None. S.C. Kumar: None. H. liao: None. Introduction: Anaplastic thyroid carcinoma (ATC) is a rare but highly aggressive thyroid cancer accounting for < 2% of cases, characterized by its rapid growth, extensive local invasion, and poor prognosis. Distinguishing ATC from other high-grade sarcomas, such as leiomyosarcoma, is challenging due to shared morphological features and overlapping immunoprofiles. We present a case involving a 73-year-old male presenting with rapidly growing neck mass, leading to diagnostic challenges differentiating between ATC and high-grade sarcomas. Case presentation: A 73-year-old male presented to ED with a rapidly growing painful neck mass for last 3 months, associated with dysphagia, dyspnea & dysphonia. He denied any fever, chills, weight loss and symptoms of hyperthyroidism or hypothyroidism. No personal or family history of thyroid cancer. On physical exam: vitals were normal, Neck exam revealed a left sided neck mass, mobile with deglutition, hard in consistency associated with hoarseness of voice. No stridor or wheeze noted on auscultation. Physical exam was otherwise normal. Laboratory tests showed normal CBC, CMP and TSH 1.45 mIU/L, T4 9.7 ug/dl. CT neck with contrast showed 5.4 x 5.6 x 8.2 cm large lobulated left thyroid mass with rightward airway deviation & substernal extension. Ultrasonogram of thyroid showed 9.6 x 5.3 x 3.3 cm left thyroid lobe with internal calcifications & extrathyroidal extension with several abnormal appearing cervical lymph node, largest measuring 4.9 x 2.4 x 3.3 cm. CT chest/abdomen/pelvis with contrast showed multiple bilateral lung nodules measuring up to 1.5 cm and 1.4 x 1.3 cm left gluteal soft tissue mass. IR-guided left neck mass biopsy was suggestive of primary spindle cell neoplasm with initial immunoprofiles consistent with a high-grade sarcoma, favoring leiomyosarcoma. Given the rapid growth of the neck mass with associated dyspnea, left thyroidectomy was performed and surgical pathology was suggestive of a high-grade sarcoma. However, subsequent pathology review made a final diagnosis of ATC, based on morphologic & immunohistochemical profile showing tumor cells strongly positive for p53 and Desmin with few cells positive for PAX-8, Cam 5.2 and CD68, and negative thyroglobulin, TTF-1, CK7, CK20, CK MNF116, pancytokeratin AE1/AE3 and CK5/6. Thyroseq revealed a distinctive molecular profile specifically positive for TERT and TP53 supporting diagnosis of ATC. Discussion: This case highlights the diagnostic dilemma posed by the resemblance between ATC and high-grade sarcomas due to overlapping clinical, morphological and immunohistology features. While both malignancies may exhibit similar morphological features, specific immunohistochemistry profiles along with molecular testing aid in distinguishing between them and guiding appropriate treatment strategies. Presentation: 6/1/2024

Chronic Invasive Fungal Sinusitis Mimicking Malignancy Post-Radiotherapy: A Case Report.

Invasive fungal sinusitis is a life-threatening form of fungal rhinosinusitis. Due to the aggressive clinical presentation and radiological appearance, there is diagnostic difficulty in differentiating invasive fungal sinusitis from a malignant process. This is even more challenging in oncological patients who have undergone previous head and neck radiotherapy, due to possibility of a recurrence of primary malignancy and radiation-induced neoplasms. We report a rare case of invasive fungal sinusitis mimicking a malignancy in a post-radiotherapy patient.Our patient was a 68-year-old male, 25-years post-radiotherapy for nasopharyngeal carcinoma. He presented with a 3-month history of purulent sputum and right facial paraesthesia. Magnetic resonance imaging showed an irregular destructive enhancing mass of the greater wing of right sphenoid and pterygoid bone with extensive extension into nearby structures. In view of extensive local and bony invasion, and a history of radiotherapy, initial suspicions were that of primary malignancy, specifically radiation-induced sarcoma, and recurrence of nasopharyngeal carcinoma. He underwent transpterygoid biopsy of the lesion, and histopathology demonstrated Aspergillus species, with no malignancy identified.Our report highlights the diagnostic difficulties in the post-radiotherapy cancer patient presenting with symptoms suggestive of aggressive sino-nasal disease. Invasive fungal sinusitis closely mimics the clinical and radiological findings of several neoplastic processes. We discuss the clinical and radiological characteristics of pathologies that may mimic invasive fungal sinusitis. Histological examination remains the gold standard for diagnosis, and early fungal staining is crucial. Furthermore, one should not presume the initial histopathological diagnosis to be confirmatory of isolated fungal disease. Repeat radiological investigations for disease resolution and histopathologic re-evaluation if required should be performed, keeping in mind possibility of coexisting malignancy.

Anaplastic thyroid cancer: A review of recent evidence and summary of an Australian institutional protocol.

Anaplastic thyroid cancer (ATC), a rare and highly aggressive malignancy, is characterized by an exceptionally poor prognosis, where the majority of patients present with extensive local invasion and/or distant metastases. 20-30% of ATCs harbor the BRAF-V600E mutation. Neoadjuvant BRAF-targeted therapy may have the potential to downstage and facilitate surgical resection for patients with locally advanced and unresectable primary tumors with BRAF mutation and may convey a survival advantage in those with metastatic disease. There is emerging evidence to support the use of other targeted agents, including multikinase inhibitors, as well as the incorporation of immunotherapy into the treatment regimen. Rapid molecular and pathological diagnosis and expert multidisciplinary discussion at specialized treatment centers are critical to expedite investigations and initiate treatment for this complex and rapidly progressive disease.

Immunotherapy-based neoadjuvant therapy followed by concurrent chemoradiotherapy in locally advanced and advanced cervical cancer: A real-world study.

e17509 Background: Locally advanced and advanced cervical cancer (CC), characterized by extensive local invasion and potential distant metastasis, present substantial clinical challenges. Although concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced CC, a considerable proportion (23%-34%) of treated pts experienced recurrence or subsequent metastasis. Recently, neoadjuvant therapy (NAT) has been proposed to increase the radiosensitivity and decreases the fraction of hypoxic cells. Particularly, immunotherapy (IO)-based NAT has shown high activity in treating CC. Moreover, IO plus CRT has shown promise in enhancing both local control and systemic response. Hence, we analyzed the efficacy and safety of IO-based NAT followed by CCRT for locally advanced and advanced CC in a real-world setting. Methods: This study retrospectively analyzed data from pts with locally advanced and advanced CC who underwent IO-based NAT followed by CCRT at Shengjing Hospital of China Medical University from January 2022 to January 2024. Outcome measures included complete response (CR), partial response (PR), objective response rate (ORR), progression free survival (PFS), and safety. Tumor responses after neoadjuvant or CCRT therapy were evaluated using RECIST v1.1 and PFS was analyzed with the Kaplan-Meir method. Safety was assessed by adverse events (AEs) referring to CTCAEs v 5.0. Results: A total of 20 pts (median age 57 years, range, 39-72) were included in this analysis, with 15% at stage IIIB, 60% at IIIC, 10% at IVA, and 15% at IVB. Eight (40%) pts received 1 cycle of neoadjuvant IO, 8 (40%) received 1-4 cycles of neoadjuvant IO + chemotherapy, and 4 (20%) received 2 cycles of neoadjuvant IO + bevacizumab (Bev) + chemotherapy. After NAT, all 20 pts received CCRT. In the overall population, ORR after NAT was 55% (11/20), with 5% CR and 50% PR. Regarding different IO-based NAT regimens, objective responses were achieved in 1 of 8 (12.5%) pts receiving neoadjuvant IO, 6 of 8 (75%) pts receiving neoadjuvant IO + chemotherapy, and 4 of 4 (100%) pts receiving neoadjuvant IO + Bev + chemotherapy. After CCRT, 6 (30%) pts had a CR and 7 (35%) pts had a PR, resulting in an ORR of 65.0%. At a median follow-up of 14.9 months, the median PFS was not reached, with a 12-month and 24-month PFS rates of 68% and 56%, respectively. The most common treatment-related AEs during NAT were white blood cell count decreased (50%) and neutrophil count decreased. Conclusions: IO-based NAT followed by CCRT were effective and well-tolerated for pts with locally advanced and advanced CC. This treatment modalities may provide a potential therapeutic strategy for locally advanced and advanced CC.

Diagnosis and Management of Verrucous Carcinoma of the Esophagus

Verrucous esophageal carcinoma is an extremely rare subtype of squamous cell carcinoma of the esophagus that is characterized by a friable exophytic mass but is often deceptively low-grade and superficially well-differentiated on mucosal biopsies, making pathologic diagnosis challenging. Distant metastasis is rare in these tumors. Therefore, early diagnosis is crucial as surgical resection is frequently curative. Conversely, delay in diagnosis can lead to extensive local invasion and result in severe morbidity and death. In this article, we will outline the history of verrucous esophageal carcinoma, review the current clinical understanding based on cases of verrucous carcinoma described thus far, and discuss recent advances in understanding of the pathogenesis of verrucous esophageal carcinoma that may aid in molecular diagnostics.

The dopamine receptor D1 inhibitor, SKF83566, suppresses GBM stemness and invasion through the DRD1-c-Myc-UHRF1 interactions.

Extensive local invasion of glioblastoma (GBM) cells within the central nervous system (CNS) is one factor that severely limits current treatments. The aim of this study was to uncover genes involved in the invasion process, which could also serve as therapeutic targets. For the isolation of invasive GBM cells from non-invasive cells, we used a three-dimensional organotypic co-culture system where glioma stem cell (GSC) spheres were confronted with brain organoids (BOs). Using ultra-low input RNA sequencing (ui-RNA Seq), an invasive gene signature was obtained that was exploited in a therapeutic context. GFP-labeled tumor cells were sorted from invasive and non-invasive regions within co-cultures. Ui-RNA sequencing analysis was performed to find a gene cluster up-regulated in the invasive compartment. This gene cluster was further analyzed using the Connectivity MAP (CMap) database. This led to the identification of SKF83566, an antagonist of the D1 dopamine receptor (DRD1), as a candidate therapeutic molecule. Knockdown and overexpression experiments were performed to find molecular pathways responsible for the therapeutic effects of SKF83566. Finally, the effects of SKF83566 were validated in orthotopic xenograft models in vivo. Ui-RNA seq analysis of three GSC cell models (P3, BG5 and BG7) yielded a set of 27 differentially expressed genes between invasive and non-invasive cells. Using CMap analysis, SKF83566 was identified as a selective inhibitor targeting both DRD1 and DRD5. In vitro studies demonstrated that SKF83566 inhibited tumor cell proliferation, GSC sphere formation, and invasion. RNA sequencing analysis of SKF83566-treated P3, BG5, BG7, and control cell populations yielded a total of 32 differentially expressed genes, that were predicted to be regulated by c-Myc. Of these, the UHRF1 gene emerged as the most downregulated gene following treatment, and ChIP experiments revealed that c-Myc binds to its promoter region. Finally, SKF83566, or stable DRD1 knockdown, inhibited the growth of orthotopic GSC (BG5) derived xenografts in nude mice. DRD1 contributes to GBM invasion and progression by regulating c-Myc entry into the nucleus that affects the transcription of the UHRF1 gene. SKF83566 inhibits the transmembrane protein DRD1, and as such represents a candidate small therapeutic molecule for GBMs.

Canine phaeochromocytoma: a guide to diagnosis and treatment

Phaeochromocytomas are neuroendocrine tumours arising from chromaffin cells of the adrenal medulla. Clinical signs are primarily associated with excessive catecholamine secretion and, to a lesser extent, with the space-occupying or invasive nature of the tumour. The diagnosis of phaeochromocytoma relies on clinical suspicion, biochemical testing, diagnostic imaging and histopathology. Biochemical testing mainly depends on the measurement of levels of plasma or urinary metanephrines, with normetanephrine demonstrating superior diagnostic performance compared to metanephrine. Adrenalectomy is the treatment of choice, but may not be possible in cases with extensive local invasion, concurrent disorders or distant metastasis. Contrast-enhanced computed tomography is recommended for surgical planning and metastasis screening. Vascular invasion is frequently observed, yet surgery remains a viable option in many cases. Recent studies question the necessity of alpha-blockade before surgery, and randomised controlled clinical trials are necessary to evaluate this. Long-term survival is often seen in dogs that survive the perioperative period. For patients in which surgery is not deemed feasible, medical treatment with tyrosine-kinase inhibitors may be considered. Given the current scarcity of effective medical treatment, there is an urgent need to identify novel therapeutic options. This review provides recommendations on the diagnosis and management of canine phaeochromocytoma.

Prevalence and interpretation of AFF immunostain of DEK::AFF2 fusion-associated papillary squamous cell carcinoma in a retrospective cohort of recurrent sinonasal papillomas.

DEK::AFF2 fusion-associated papillary squamous cell carcinoma is a novel entity characterized by its unique translocation and malignant clinical course. In this study, AFF immunohistochemistry (IHC) was performed in recurrent sinonasal papillomas for reviewing the prevalence of undiagnosed DEK::AFF2 carcinomas and to investigate the performance of AFF IHC in diagnosis of DEK::AFF2 carcinomas. Recurrent sinonasal papillomas after surgical excision in a two-decade period were retrieved. Histologic slides were reviewed for features of DEK::AFF2 carcinoma. AFF IHC was performed, and cases with any (> 1%) nuclear positivity were validated by DEK break apart fluorescence in situ hybridization. Totally 43 cases were included, comprising 28 inverted, 6 exophytic, one oncocytic, and 8 non-specified sinonasal papillomas. Five (11.6%) cases exhibited positivity to AFF IHC. Three cases exhibited patchy weak to moderate staining intensity predominantly in a granular cytoplasmic pattern. Two cases exhibited strong and diffuse (> 90%) nuclear staining. Cases showing weak staining were negative for DEK rearrangement, while those with strong staining were positive. Both cases of DEK::AFF2 carcinoma showed aggressive behavior with extensive local invasion and nodal metastasis. Background stromal plasma cells, when present, consistently showed strong and diffuse staining. AFF IHC was further performed in plasmacytoma samples as control and showed strong and diffuse immunoreactivity. A significant minority of recurrent sinonasal papillomas represent DEK::AFF2 carcinomas. Granular, cytoplasmic, or incomplete AFF staining should be considered as negative. In view of the rarity of DEK::AFF2 carcinomas, plasma cells and plasma cell neoplasms are potential for internal and surrogate external controls.

More aggressive biological behavior in pediatric than in adult papillary thyroid carcinoma

ObjectivePapillary thyroid carcinoma (PTC) remains a common malignancy of the endocrine system in children and adolescents. This study aimed to investigate the differences in clinical characteristics between children and adults with PTC. MethodsA total of 360 patients [ 308 adults (≥20 years) and 52 children and adolescents (<20 years)] with PTC who underwent thyroid surgery in our center from 2017 to 2022 were retrospectively analyzed. Statistical analysis and comparisons of the clinicopathological data and tumor characteristics between children and adults were performed. ResultsAmong all enrolled patients, the mean tumor diameter was 26.21 ± 12.72 mm in the pediatric group, while that in the adult group was 11.62 ± 10.21 mm, which was a significant difference (p < 0.001). Pediatric patients were more prone to central lymph node metastasis (90.38% vs. 49.35%, p<0.001), lateral lymph node metastasis (78.85% vs. 45.7%, p<0.001), capsular invasion (90.38% vs. 63.96%, p<0.001) and extrathyroidal extension (61.54% vs. 15.26%, p＜0.001) than adult patients. However, the pediatric group had a lower BRAFV600E mutation rate (54.76% vs. 87.7%, p < 0.001) and lower incidence of Hashimoto's thyroiditis (15.38% vs. 30.84%, p = 0.023) than the adult group. There were no significant differences in clinicopathological factors, such as sex, multifocality and hypothyroidism. ConclusionsPediatric patients were more likely to present with advanced disease at diagnosis, including larger tumor volume, more lymph node metastasis, more extensive local invasion, and lower rates of BRAF mutation and concomitant Hashimoto's thyroiditis. Therefore, appropriate surgical management and comprehensive treatment decisions are needed for pediatric patients with PTC.

Dermatofibrosarcoma Protuberans; Case Report in a Pediatric Patient

Dermatofibrosarcoma protuberans (DFSP) is a rare and locally aggressive mesenchymal neoplasm arising from the dermal and subcutaneous tissues. It typically manifests as a slow-growing, firm, protuberant or plaque-like lesion on the skin. DFSP predominantly affects young to middle-aged adults, with a slight predilection for females. This tumor exhibits a distinctive infiltrative growth pattern, characterized by tumor cells invading the surrounding tissues, including the deep subcutaneous layers and the underlying fascia. Histopathologically, DFSP presents characteristic features, such as the presence of spindle-shaped tumor cells arranged in a "storiform" pattern, as well as the presence of a prominent "honeycomb" appearance due to the presence of multinucleated giant cells. Immunohistochemical staining is essential to confirm the diagnosis, with positivity for CD34 being a hallmark of DFSP. Although DFSP rarely metastasizes, its extensive local invasion and high recurrence rate necessitate a wide surgical excision with clear margins as the mainstay of treatment. The use of Mohs micrographic surgery or adjuvant radiation therapy has demonstrated favorable outcomes in cases with challenging anatomical locations or microscopically positive margins. Imatinib mesylate, a tyrosine kinase inhibitor, has also emerged as a promising systemic therapy for advanced or unresectable DFSP, particularly cases with the COL1A1-PDGFB gene fusion, which represents the molecular hallmark of DFSP. Early diagnosis and appropriate management are crucial to achieving optimal outcomes in DFSP. This article provides a comprehensive review of the clinical, histopathological, and molecular aspects of DFSP, highlighting the significance of a multidisciplinary approach to ensure accurate diagnosis and tailored therapeutic strategies for patients affected by this rare dermatological neoplasm.

Paravertebral paraganglioma with spinal extension: a case report

BackgroundParagangliomas are rare neuroendocrine tumors. While paragangliomas of the spine are rare, those located in non-cauda equina areas with spinal canal extension are even rarer.Case presentationWe present a case of a 23-year-old female of African descent with a primary thoracic paraganglioma with intervertebral extension resulting in displacement and compression of the spinal cord and extensive local invasion of the surrounding structures. This paraganglioma was functional with typical symptoms of catecholamine excess. Despite the aggressive nature of the paraganglioma, the patient only had isolated sensory symptoms in the left shoulder. Adequate alpha and beta-blockade were instituted prior to her undergoing surgery with near-total resection and complete preserved neurology. There was no underlying pathogenic genetic mutation found.ConclusionsEven though rare, paraganglioma should be considered in the differential diagnosis of spinal tumors. Genetic testing should be performed in patients with paragangliomas. One should exercise extreme caution in treating such rare tumors that may cause neurological deficits and careful surgical planning should be undertaken to avoid possible catastrophic complications.

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.

Intra-abdominal Cystic Lymphangiomas: The Vanderbilt Experience

IntroductionLymphangiomas are rare, cystic tumors that represent congenital malformation of the lymphatic vessels. We reviewed our institution's experience treating abdominal lymphangiomas with the purpose of describing the clinical features, management, and outcomes of this rare pathology. MethodsThis is a single-institution, institutional review board-approved retrospective review of abdominal lymphangiomas presenting between January 2010 and February 2021. The diagnosis of lymphangioma was made on histopathology from either endoscopic or excisional biopsy of the lesion. Demographics, diagnostic imaging, histopathologic characteristics, and outcomes were analyzed. ResultsWe identified 48 patients, of whom 29 (60%) were female, >18 y (38; 79%), with a mean age of 43 y at the time of diagnosis (range, 4 d-87 y). Tumors ranged in size from <1 cm to 30 cm. Only 1/3 were symptomatic, most commonly with abdominal pain (9; 19%) On preoperative imaging, mural nodules or thickened walls were present in one case, in which pathology was consistent with benign lymphangioma. The majority of lymphangiomas were associated with the small bowel or its mesentery (31; 65%), followed by the colon/omentum (7; 15%). Most patients underwent surgical excision (29; 60%) with incomplete excision in one patient due to extensive local invasion, and three (10%) patients required multivisceral resection. The median duration of the follow-up was 13 mo (range, 1-105 mo), during which time, none of the patients developed malignancy. ConclusionsMost abdominal lymphangiomas arise from the small bowel and are found incidentally and have a favorable prognosis. Resection should be reserved for symptomatic lesions or when there is a diagnostic uncertainty.

Primary Tumor Recurrence after Chemoradiotherapy in Limited Stage Small Cell Lung Cancer

<h3>Purpose/Objective(s)</h3> Accounting for 13-15% of lung cancer, small cell lung cancer (SCLC) is typically characterized by more extensive local invasion and more frequent metastases compared with other subtypes. Although SCLC is sensitive to chemoradiotherapy, 25% of the patients with limited stage SCLC would meet local regional relapse. Although thoracic radiation had significantly improved local control, primary tumor recurrence is common in clinic. So far, we had little acquaintance of the local relapse details to help us to make progress in the thoracic radiation. To investigate the patterns of patients with local regional recurrence and the prognosis of primary tumor recurrence, we proposed this study. <h3>Materials/Methods</h3> We searched patients with pathological diagnosis of SCLC, with disease of limited stage, received systemic chemotherapy and thoracic intensity modulate radiotherapy at our center with available follow-up records between August 1^st, 2006 and May 31^st,2014. Patients with intrapulmonary recurrence or regional lymph nodes recurrence by the last follow up time, without diffused lung metastasis were selected. All the patients received involved field thoracic radiotherapy with dose of 2Gy per fraction per day. Data regarding patient demographics and treatments. The first local recurrent sites were recorded. Local regional relapse time was calculated from the first day of the treatment delivery to the diagnosis of primary tumor or regional lymph nodes. Overall survival was calculated from the first day of the diagnosis of local relapse to the death using Kaplan Meir Method. <h3>Results</h3> We identified 482 patients with a diagnosis of limited stage SCLC. Among these, 125 patients fulfilled the eligibility criteria. The median dose of radiotherapy is 60Gy. The median local relapse time was 12.97 months. Primary tumor recurrence, ipsilateral hilar and/or mediastinal lymph node recurrence, contralateral hilar and/or lymph node recurrence, and supraclavicular lymph node recurrence, were observed in 92 patients (73.6%), 49 patients (39.2%), 1 patient (0.8%) and 13 patients (10.4%), respectively. There were 26 patients with multisite local recurrence. Out-field relapse was observed in 6 patients (4.8%). The median follows up time was 34.7 months. After second line therapies, the median survival time for these patients diagnosed as recurrent disease was 10.5 months. Of the 92 patients with primary tumor recurrence, 25 patient received re-radiation and 39 patients also met distant metastasis. Median survival time of patients with primary tumor recurrence is slightly shorter than the others (9.9months vs. 12.0months). <h3>Conclusion</h3> For patients with limited stage SCLC who received chemoradiotherapy, primary tumor recurrence is still the leading course in local regional relapses and accompanied by worse survival. Accordingly, simultaneous integrated boost might be taken into consideration to primary tumor. Involved field radiation is reasonable with low out-field local recurrence.

Sinonasal Undifferentiated Carcinoma with Failed Response to Induction Chemotherapy.

Sinonasal undifferentiated carcinoma (SNUC) is a rapidly growing malignancy with a propensity for extensive local invasion. Multimodal therapy, including surgery, radiotherapy, and chemotherapy, is the standard approach to treatment, but the optimal sequence and combination of these modalities are uncertain. Induction chemotherapy is being increasingly utilized based on recent reports that show better outcomes for patients who respond to chemotherapy and the ability to determine further course of treatment. We present a unique case of a patient with locally advanced SNUC that did not respond to induction chemotherapy and a review of the available literature relating to the management of this rare malignancy.

Abstract 1743: Identification of mesothelin binding peptide for targeted therapy against pancreatic cancer

Abstract Pancreatic cancer is the main cause of cancer-related deaths worldwide and is difficult to diagnose before the extensive local invasion and distant organ metastasis. Mesothelin is abnormally overexpressed in tumors such as ovary cancer and pancreatic cancer. Studies show a significant link between mesothelin overexpression and short survival in patients with pancreatic cancer. In this study, we screened a phage displayed-peptide library for peptides that selectively bind to mesothelin using mesothelin-overexpressing cells. After five rounds of screening, we selected a 9-mer peptide (named MSLN-Pep) that preferentially bound to mesothelin-high pancreatic cancer cells such as ASPC-1 and Panc-1 cells over mesothelin-low cells such as HEK 293 cells. MSLN-Pep was efficiently internalized into ASPC-1 cells and inhibited the cell migration and invasion while little affected the phosphorylation of Akt. Moreover, a MSLN-Pep-guided proapoptotic peptide (MSLN-Pep-KLA) exerted selective cytotoxicity against pancreatic cancer cells over mesothelin-low cells. MSLN-Pep-KLA when combined with gemcitabine, a chemotherapeutic agent against pancreatic cancer, sensitized ASPC-1 cells to the gemcitabine treatment. These results suggest that MSLN-Pep is a promising tool for a targeted therapy against pancreatic cancer expressing mesothelin at high levels. Citation Format: Min-Sung Park, Byungheon Lee. Identification of mesothelin binding peptide for targeted therapy against pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1743.

P39.01 Long-Term Outcomes and Characteristics of Unresectable Locally Advanced Thymic Malignancies

Surgical resection of patients with thymic malignancies with extensive local invasion can be challenging, and the benefit resulting from an incomplete resection is unclear. We sought to define the characteristics, treatment approaches and reasons for unresectability in patients with localized, unresectable thymic tumors and analyze their long-term outcomes Retrospective review of patients with localized, unresectable thymic tumors treated at our institution between 1996-2019. Patients who had surgical exploration only without any resection, surgical exploration with incomplete (R2) resection, and patients who were deemed unresectable and treated non-operatively were included in the study cohort. We analyzed demographics, radiographic findings, pathology, treatment details, and patterns of progression and survival. Descriptive statistics and Kaplan-Meier survival analyses were performed Fifty-nine patients were treated over the study period, 32 with thymoma (54%), 23 with thymic carcinoma (39%) and 4 with thymic carcinoid (7%). Almost all patients were TNM Stage III or IV. Nine patients (15%) were treated non-surgically (NS) and underwent definitive radiation therapy or chemoradiotherapy alone, 14 (24%) patients had surgical exploration only (EO) without resection, and 36 (61%) patients had surgical exploration with incomplete resection (IR). Among the patients who were explored (EO and IR), the most common intraoperative finding was invasion of great vessels or the myocardium (66%), disseminated pleural or lung metastases (14%), or both local invasion and intrathoracic dissemination (14%). Among the NS group, patients were deemed unsuitable for surgery due to the presence of unresectable metastases (22%), great artery involvement (56%), great vein involvement (11%), or severe comorbidities (11%). Forty-one patients (69%) developed progression (31 loco-regional; 10 distant) while 18 patients (31%) had stable disease during the observation period. Patients with unresectable thymoma had significantly longer overall survival (OS, p=0.02) compared to thymic carcinoma (median OS thymoma = 7.5 years; thymic carcinoma = 3.2 years). There was no significant difference in OS (p=0.2; Figure) or PFS (p=0.1) between IR and NS/EO patients. The median OS for IR patients was 4.6 years and 6.9 years for NS/EO patients. The median PFS was 0.8 years for patients in the IR group, and 1.6 years for those who had no resection (NS/EO) Despite the presence of unresectable locally advanced disease, patients with advanced thymic malignancies exhibited long-term survival regardless of the primary treatment modality. In our series, patients who underwent incomplete surgical resections did not appear to fare any better than patients who underwent exploration only or non-operative treatment

Synchronous Malignant Pheochromocytoma With Renal Cell Carcinoma: A Case Report

Introduction: In the US, Pheochromocytoma/paraganglioma incidence is estimated to be 2–8 per 1 million people each year with around 100–200 of these cases being malignant. Malignant pheochromocytoma is defined by documented presence of metastases or evidence of extensive local invasion. There are certain genetic syndromes which are also associated with renal cell carcinoma, including SDHB mutations type 4, VHL disease and familial pheochromocytoma. These syndromes are important to recognize as they may signify a worse prognosis. Here, we describe a case of co-occurrence of malignant PC with renal cell carcinoma.Case Report: A 53-year-old Hispanic male with history of HTN and recently diagnosed metastatic pheochromocytoma was admitted for surgical debulking of the left retroperitoneal/adrenal and renal masses. Symptoms began five months prior after he presented with an ischemic stroke in the setting of labile hypertension. He was diagnosed with a 6.3 x 4.6 x 6.8 cm incidental left retroperitoneal mass and suspicious left renal mass on CT imaging but also noted several lytic bony lesions concerning for bone metastasis. A spinal biopsy was obtained which was consistent with a well-differentiated metastatic neuroendocrine tumor. Laboratory evaluation was notable for Chromogranin A level of 6959ng/mL (25–140). He was started on Lanreotide. Given persistently difficult to control HTN he underwent work up for secondary hypertension. Hormonal evaluation was notable for plasma free metanephrine of 534pg/mL (<57pg/mL), normetanephrine 6155pg/mL(<148pg/mL), and total metanephrine of 6689pg/mL (205pg/mL) consistent with metastatic Pheochromocytoma. After appropriate alpha blockade he underwent left adrenalectomy, nephrectomy and liver tumor microwave ablation. Pathology was consistent with an 8.7cm pheochromocytoma with extensive retroperitoneal soft tissue invasion and PASS score of 9 as well as a 3.6 cm renal cell (clear cell-papillary type) carcinoma. On follow up, Plasma metanephrine decreased significantly postoperatively to a free metanephrine of 28pg/ml, normetanephrine 1153pg/ml, and total metanephrine of 1181pg/mL. He was referred for genetic testing but unfortunately, he was readmitted one month later with cerebral hemorrhage and expired.Conclusion: Advancements in genetics have led to improved understanding of the molecular etiologies of pheochromocytomas. A number of genetic defects are associated with PC and RCC, including SDHB mutations type 4, VHL and familial pheochromocytoma. Our case underscores the high morbidity and mortality in patients with metastatic PC with RCC and perhaps the catastrophic outcomes in such patients. Assessing patient’s genetics in these cases is now the standard of care, however further research studies are warranted to better understand the significance of tumor genetics on prognosis and management.