Primary Malignancy Research Articles

Establishment and Clinical Significance of the Patient-Derived Xenograft Model of Colorectal Cancer.

Patient-derived xenograft (PDX) models are widely acknowledged for their ability to reflect the heterogeneity of humancancers and can be used to improve preclinical models. In this study, we evaluatedthe factors affecting the tumor formation rate ofthe PDX colorectal cancer (CRC)model and conducted preliminary drug sensitivity tests. CRC patients who underwent elective surgery at Shaoxing People's Hospital from November 2019 to October 2020 were included. The tumor tissue obtained from surgery was transplanted to the back of NSG mice, and the PDX model was established and subcultured to the F3 generation. Factors that affected tumorigenicity were analyzed and compared histologically. Drug interventions included 5-fluorouracil, oxaliplatin, and propofol. Sixty CRC patients were included in this study, and tumorigenesis was observed in CRC tissue derived from 37 cases (62%). The primary tumor malignancy degree (tumor stage and degree of cell differentiation), preoperative carcinoembryonic antigen level, and tumor location in CRC patients could affect the tumorigenicity of the PDX model. Histopathological analysis of CRC-PDX transplanted tumor tissue was highly consistent with the patient's tumor tissue. All four chemotherapy regimens could inhibit tumor growth and cause tumor tissue damage. Propofol could inhibit diarrhea in mice and protect intestinal mucosa. The CRC-PDX model established in this study can maintain the biological characteristics of primary tumors and can be used as a reference model for the individualized treatment of CRC patients. The degree of malignancy of the primary tumor is the primary factor affecting the tumorigenesis rate of the PDX model.

Second malignancy in advanced or recurrent non-small cell lung cancer after the advent of molecular targeted drugs and immunotherapy.

This study aimed to investigate the characteristics of patients with recurrent or advanced non-small cell lung cancer (NSCLC) treated with tyrosine kinase inhibitors (TKIs) or immune-checkpoint inhibitors (ICIs) who developed secondary malignancies, as well as evaluate the impact of these secondary malignancies on the course of lung cancer. This study included 112 patients with postoperative recurrent or advanced NSCLC, who received TKIs, ICIs, or immune combination therapy as the primary treatment modality between April1, 2013, and March 31, 2020, and achieved long-term survival (≥2 years). Secondary malignancies were defined as newly diagnosed cancers in other organs occurring after NSCLC treatment initiation. Among the 112 patients, 10 (8.9%) developed 12 carcinomas, including third primary malignancies. Univariate analysis, considering secondary malignancies as the outcome, revealed a non-significant trend towards a higher incidence of secondary malignancies in smokers compared to non-smokers. This study found that 8.9% of patients with advanced NSCLC who received TKIs, ICIs, or immune combination therapy and survived ≥2 years developed secondary malignancies. This underscores the importance of early diagnosis and treatment, even during lung cancer treatment, to identify suspicious lesions in other organs either via imaging or physical examinations.

Pathways to cancer care after a suspected cancer diagnosis in the emergency department: a survey of emergency physicians across Ontario.

Little is known about how patients are managed after a suspected cancer diagnosis through the emergency department. The objective of this study was to examine the ED management, specifically referral practices, for ten suspected cancer diagnoses by emergency physicians across Ontario and to explore variability in management by cancer-type and centre. An electronic survey was distributed to emergency physicians across Ontario, asking about referral practices for patients who could be discharged from the ED with one of ten suspected cancer diagnoses. Options for referral included: in-ED consult, outpatient medical or surgical specialists, surgical or medical oncology, and specialized cancer clinics. Data were described using frequencies and proportions. Variance partition coefficients were calculated to determine variation in responses attributed to differences between hospitals, with physicians nested within hospitals. 262 physicians from 54 EDs responded. Across most cancers, emergency physicians would refer to surgical specialists for further work-up; however, this ranged from 30.2% for lung cancer to 69.5% for head and neck cancer. For patients with an unknown primary malignancy, most physicians would refer to internal medicine clinic (34.3%) or obtain an in-ED consult (25.0%). Few physicians would refer directly to surgical or medical oncology from the ED. Comments suggest this may be due to oncologists requiring tissue confirmation of malignancy. Most referrals to specialized clinics were for suspected lung (30.2%) or breast cancer (19.5%); however, these appear to only be available at some centres. Variance in referrals between hospitals was lowest for breast cancer (variance partition coefficient = 8.6%) and highest for unknown primary malignancies (variance partition coefficient = 29.8%). Physician management of new suspected cancer varies between EDs and is specific to cancer type. Strategies to standardize access to cancer care in a timely and equitable way for patients with newly suspected cancer in the ED are needed.

12556 Medullary Thyroid Cancer With Persistent Elevation Of Carcinoembryonic Antigen: Case Report

Abstract Disclosure: M.S. Campana: None. Introduction: Medullary thyroid Cancer (MTC) is a rare neuroendocrine tumor that originates from thyroid parafollicular C-cells and represents 5 % of all thyroid cancers. MTC can be sporadic (75%) or hereditary (25%) associated with multiple endocrine neoplasia type 2 syndrome (MEN2). Serum calcitonin (Ctn) and carcinoembryonic antigen (CEA) are its tumor markers. We report a case of persistently elevated CEA levels despite an undetectable Ctn in a patient with MTC after initial thyroid lobectomy. Description of the case: A 42-year-old woman self-identified a neck lump after intentional weight loss. A neck US showed a right lobe thyroid nodule which resulted as suspicious for malignancy (Bethesda V) with subsequent right lobectomy. Pathology reported a 2.6 cm unexpected MTC with negative surgical margins, extrathyroidal extension, angioinvasion, and lymphatic invasion. No cervical lymph nodes (LNs) were removed. Immunohistochemistry was positive for CEA, chromogranin A, synaptophysin, and Ctn. T2 Nx. One month after lobectomy, the Ctn was 10.5 (0-3.0 pg/mL) and CEA 205.2 (0-3.0 ng/mL Non-smoker; 0-5.0 ng/mL smoker). The patient was then referred to our clinic for further management. Laboratories showed normal serum calcium, PTH, and fractionated plasma metanephrine/normetanephrine. A 2-month post-operative Ctn was undetectable, but CEA was elevated at 24.5. Subsequently, we broaden imaging studies to include neck US, CT neck /chest with contrast, and MRI abdomen pelvis with contrast. The only remarkable finding was a 6.7 cm pelvic mass with normal Ca-125. Genetic testing was negative for germline RET, ruling out MEN2. Patient underwent completion left lobectomy with prophylactic bilateral central neck dissection. Pathology showed benign thyroid parenchyma with multinodular hyperplasia and 0/12 LNs. Because of concerning pelvic mass, the patient was referred to OB/GYN. She underwent a laparoscopic bilateral salpingo-oophorectomy. Pathology showed a follicular ovarian cyst, negative for malignancy. A year post-completion total thyroidectomy Ctn remains undetectable, and a CEA is normal at 1.3. Discussion: Because Ctn was already undetectable 1 month after lobectomy with persistent elevated CEA a complete total thyroidectomy with prophylactic bilateral central neck dissection was indicated to achieve operative cure. Ctn is specific to MTC but variable. CEA is more reproducible with less variability; however, it is not specific to MTC and can also be elevated in smokers, benign breast and genitourinary disease, emphysema, cirrhosis, and cancer of colon, rectum, liver, genitourinary, and lung. If residual disease is present, Ctn tends to be proportionally more elevated than CEA. When the opposite occurs, poorly differentiated MTC with possibility of distant metastases vs. a second primary malignancy vs. a distant benign neoplasm known to elevate CEA need to be ruled out. Presentation: 6/2/2024

Paraneoplastic Optic Neuropathy

The paraneoplastic syndrome may occur in tissues that are distant from the primary malignancy or its metastasis and may include various signs and symptoms. It can negatively affect ocular tissues, which may threaten visual acuity, especially if it affects the retina and optic nerve. When it impacts the optic nerve, it is called paraneoplastic optic neuropathy. PON is a rare, subacute and progressive disease that can frequently affects both eyes. Its signs and symptoms can be very similar to other types of optic neuritis, which can lead to confusion and misdiagnosis. In this study, we aimed to outline the clinical features, pathogenesis, diagnosis, and management of PON.

Immune-related glycosylation genes based classification predicts prognosis and therapy options of osteosarcoma

Osteosarcoma is the most common primary bone malignancy, with a very poor prognosis. Aberrant glycosylation is close involvement in osteosarcoma. Accordingly, this study aimed at investigating the role of glycosylation genes in the prognosis and therapy options of osteosarcoma. The microenvironment of osteosarcoma was assessed using estimate algorithm. A total of 20 immune-related glycosylation genes (IRGGs) was identified using Pearson correlation analysis. Accordingly, osteosarcoma patients were divided into C1 and C2 type using consensus clustering. Multiple algorithms (Xcell, MCP-counter, ssGSEA, epic, quantiseq), cancer immune cycle analysis, and GSVA were applied to estimate the immune, molecule and metabolism characteristics of osteosarcoma, indicating that C1 type was featured with high immune infiltration, high glycosylation, enriched MEK signaling, and good prognosis, while C2 type was characterized by more metastasis, enriched immunotherapy-positive gene signatures, high tumor mutation burden, and poor prognosis. Results from TIDE algorithm and immunotherapy datasets suggested the C2 type’s preference of immune checkpoint inhibitors (ICIs), while data of GDSC, CMap analysis and cell experiments indicated that C1 type was sensitivity to MEK inhibitor PD0325901. In addition, univariate Cox and Lasso analysis was combined to establish an IRGGs’ risk score containing 6 genes (B3GNT8, FUT7, GAL3ST4, GALNT14, HS3ST2, and MFNG). The data of DCA and ROC indicated its well prediction of prognosis in osteosarcoma. Finally, cellular location analysis showed that the 6 genes not only distributed in tumor cells but also in immune cells. In summary, the classification and risk score based on IRGGs effectively predicted the prognosis and therapy options of osteosarcoma. Further studies on IRGGs may contribute to the understanding of cancer immunity in osteosarcoma.

A study of the association of vitamin D receptor (VDR) as a predictive biomarker for immune checkpoint inhibitor therapy with immune invasion in colon adenocarcinoma

Colon adenocarcinoma(COAD) is a primary and aggressive malignancy with the fifth highest mortality rate among cancers, and it is important to discover new strategies. The online database was used to analyze the correlation between Vitamin D receptor (VDR) and COAD, and further explore the immune infiltration and related gene networks.The expression and methylation levels of VDR was analyzed by using Timer database, GEPIA platform and UALCAN database. GeneMANIA database was used to analyze and obtain gene networks that are closely linked to VDR. UALCAN database was used to score the gene effects of VDR in colorectal cancer cell lines. The cBioPortal database was used for the detection of gene mutations. The survival curve analysis was carried out using the GEPIA database. The relationship between VDR expression and immune cell infiltration was analyzed by using the timer database and TISIDB database. TISIDB database was used to obtain VDR-related drug targets.The expression of VDR was significantly lower in COAD(p<0.05). The methylation level of VDR was significantly higher in COAD (p<0.05). The gene mutation rate of VDR in COAD was 2 %. OS and DFS were not associated with changes in the VDR gene in patients with COAD. VDR expression was correlated with CD4+T cell infiltration, macrophage infiltration, neutrophil infiltration, and dendritic cell infiltration. VDR has a clear correlation with ADORA2A, BTLA, CD160, CD244, CD274, CD96, CSF1R, CTLA4, HAVCR2, IL10, IDO1, LAG3, LGALS9, PDCD1, PDCD1LG2, PVRL2, TGFB1, TGFBR1, TIGIT and VTCN1.The expression of VDR is associated with immune infiltration in patients with COAD. VDR may be a new candidate biomarker for determining the level of immune infiltration and predicting immune checkpoint inhibitor therapy.

8411 Ectopic ACTH-dependent Cyclical Cushing’s Syndrome- the Art of Hide-and-seek

Abstract Disclosure: H. Mon: None. A. Kapoor: None. S. Qureshi: None. M. Martineau: None. K. Meeran: None. Case report: A 72-years-old lady was admitted with hypokalaemia, hyperglycaemia with metabolic alkalosis with background hypertension, type2 diabetes, osteoporosis and right-sided breast cancer treated with chemotherapy and radiotherapy 3years ago. She was previously seen in Endocrinology Clinic for similar episode and deemed not having Cushing’s or Conn’s syndrome on workup. During this admission, although there was no obvious Cushingoid appearance, there was refractory hypokalaemia. On further exploration, there were previous admissions with similar episodes in UK and in her home country, within the same year, a few months apart. Therefore, endocrinology workup was conducted for suspected cyclical Cushing’s syndrome. It demonstrated raised 24-hour urinary free cortisol of 5643 nmol/24hour (reference range 0-164 nmol/24hours), unsuppressed low dose dexamethasone suppression test with cortisol level of 800 nmol/L and increased ACTH level of 429 ng/L. MRI (pituitary) showed no pituitary lesion with probable empty sella and CSF filled. However, CT (thorax) showed enlarging lesion (previously from 1cm to 1.6cm) in the left lower lobe, concerning lung metastasis or primary lung malignancy. PET scan showed left lower lobe nodule having low-grade activity with likelihood of indolent malignancy and appearances of physiologic adrenal hyperplasia. Management: Given persistently high cortisol levels during admission with ongoing hyperglycaemia and refractory hypokalaemia, metyrapone was started and titrated accordingly. Her clinical condition including potassium and cortisol levels effectively responded to metyrapone. Gallium scan was booked for detail localization with ongoing lung MDT (multidisciplinary team meeting) and neuroendocrine tumour MDT.However, after starting metyrapone, she had type 1 respiratory failure, not responding to initial antibiotics. After excluding other possible respiratory aetiologies, empirical treatment for Pneumocystosis pneumonia (PCP) was initiated, after which blood test for Beta-D-glucan was found out to be significantly raised, supporting the presumptive diagnosis. Conclusion: Our case highlighted the following interesting points 1. diagnostic challenges, due to the fluctuating nature of cyclical Cushing’s syndrome, presenting with recurrent hypokalaemia. 2. the interesting nature of likely ACTH-dependent cyclical Cushing’s syndrome, progressing into florid Cushing’s syndrome, with efficacy to metyrapone 3. rare and compelling combination of 3 conditions of Cyclical Cushing’s syndrome, being ectopic ACTH-dependent and complicated by Pneumocystosis pneumonia (PCP). Presentation: 6/1/2024

Role of Imaging in Screening for Hepatocellular Carcinoma.

Primary liver cancer is among the most common cancers globally. It is the sixth-most common malignancy encountered and the third-most common cause of cancer-related death. Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, accounting for about 90% of primary liver cancers. The majority of HCCs occur in patients with underlying cirrhosis, which results from chronic liver diseases such as fatty liver, hepatitis B and hepatitis C infections, and chronic alcohol use, which are the leading causes. The obesity pandemic has led to an increased prevalence of nonalcoholic fatty liver disease (NAFLD), which leads to nonalcoholic steatohepatitis and could progress to cirrhosis. As HCC is among the most common cancers and occurs in the setting of chronic liver disease in most patients, screening the population at risk could help in early diagnosis and management, leading to improved survival. Screening for HCC is performed using biochemical marker testing such as α-fetoprotein (AFP) and cross-sectional imaging. It is critical to emphasize that HCC could potentially occur in patients without cirrhosis (non-cirrhotic HCC), which can account for almost 20% of all HCCs. The lack of cirrhosis can cause a delay in surveillance, which could potentially lead to diagnosis at a later stage, worsening the prognosis for such patients. In this article, we discuss the diagnosis of cirrhosis in at-risk populations with details on the different modalities available for screening HCC in patients with cirrhosis, emphasizing the role of abdominal ultrasounds, the primary imaging modality in HCC screening.

7761 Unmasking The Uncommon: A Case Of Primary Adrenal Insufficiency Presenting As Severe Hypercalcemia

Abstract Disclosure: A. Misbah: None. Z. Al-Hiti: None. A. Saleh: None. M. Joda: None. K. Rajamani: None. Adrenal insufficiency is a recognized but uncommon cause of hypercalcemia. The exact mechanism remains unknown; however, it is thought to be a combination of the hypovolemic state in adrenal insufficiency leading to decreased urinary clearance, as well as increased bone resorption. We present a case of primary adrenal insufficiency presenting with severe hypercalcemia. A 41 year old female with a past medical history of osteopenia, recently diagnosed postural orthostatic tachycardia syndrome (POTS), and hyponatremia attributed to SIADH presented with complaints of weakness and poor oral intake. She also reported a history of nausea, vomiting, weight loss, fatigue, and dizziness, for the last few months. She reported feeling well prior to a COVID-19 infection a few months back. At presentation, she was hypotensive with a blood pressure of 70/50 mmHg, while her other vital signs were stable. She appeared ill, and was noted to have dry oral mucous membranes. There was no increased pigmentation noted on exam. Initial laboratory evaluation revealed sodium of 130 (135-145 mmol/L), potassium of 5.3 (3.5-5.1 mmol/L), and creatinine of 1.7 (0.5-0.8 mg/dL). She had severe hypercalcemia with a calcium level of 15.5 (8.3-10.6 mg/dL) and had a blood glucose level of 53 (70-100 mg/dL). Venous blood gas indicated metabolic acidosis. Morning cortisol was low at 1 (3-23 ug/dL). Serum ACTH was elevated at 775 (0-46 pg/mL). Cosyntropin stimulation test confirmed primary adrenal insufficiency. She underwent work-up for hypercalcemia, which revealed a suppressed PTH, normal levels of PTHrP, vitamin D, and vitamin A. Serum and urine protein electrophoresis was normal. She was initially managed in the ICU and received aggressive fluid resuscitation. She was started on stress dose of hydrocortisone, which was then tapered to physiological doses of oral hydrocortisone and fludrocortisone. Subsequent improvements were observed in blood pressure, laboratory abnormalities, and normalized serum calcium levels. She was discharged home on hydrocortisone and fludrocortisone. On follow-up, she was doing well with the resolution of her symptoms. This case highlights the importance of recognizing adrenal insufficiency as one of the causes of hypercalcemia. Although hypercalcemia as a consequence of adrenal insufficiency is well-documented, the exact prevalence is not known but is estimated to be around 6%. After excluding more common diseases such as primary hyperparathyroidism and malignancy, the possibility of adrenal insufficiency should be considered as a cause of hypercalcemia. Treatment involves hormone replacement as well as hydration, bringing resolution to symptoms. Her presentation was unique, also due to the fact that her initial symptoms were diagnosed as POTS as well as SIADH. Given the onset of symptoms after a COVID-19 infection a few months ago, there could also be a potential link between the two. Presentation: 6/3/2024

7639 A Rare Cause of Lung Adenocarcinoma with Metastasis to the Thyroid

Abstract Disclosure: E. Echevarria-Torres: None. C.G. Yap: None. K.E. Izuora: None. A rare cause of lung adenocarcinoma with metastasis to the thyroid. Metastasis to the thyroid gland from non-thyroid malignancies is rare. When metastasis occurs, presenting symptoms are typically nonspecific, representing a diagnostic challenge. With the goal of raising awareness, we present a case of lung adenocarcinoma with metastasis to the thyroid. An 85-year-old man with a history of hypertension, hyperlipidemia and 60 years smoking history presented to the endocrine clinic for evaluation of subclinical hyperthyroidism. On the physical exam, there was fullness in the right thyroid area which on ultrasound showing a large right thyroid nodule occupying the entire lobe. There was also a solid 4.5 cm x 3.4 cm x 4.6 cm nodule in the mid-anterior left thyroid lobe. Fine needle aspiration cytology of right nodule revealed malignant cells and cell block material positive for TTF-1 (Thyroid Transcription Factor 1) concerning for malignancy. The left thyroid nodule cytology was consistent with benign follicular nodule. Chest CT ordered for surgical planning showed right upper lobe pleural-based lung opacity measuring 3.7 cm x 2.9 cm with supra clavicular lymphadenopathy. Biopsy of lung mass and supra clavicular lymph nodes revealed primary lung adenocarcinoma involving the lymph nodes consistent with stage Iva (cT3NxM1b). The patient was referred to oncology for further management. Discussion: Metastatic lesions to the thyroid gland account for less than 1 % of all malignant thyroid tumors with most cases found on autopsy. This is hypothesized to be due to the rich blood supply and high iodine content of the thyroid gland. Thyroid metastasis usually presents several years after initial diagnosis and treatment of non- thyroid malignancy. Patients can present with enlarging thyroid nodules, neck swelling, dysphagia and, in rare instances, upper airway obstruction. We present a rare case of lung cancer with metastasis into the thyroid. The thyroid nodule initially palpated upon physical exam led to eventual thyroid ultrasound and subsequently to his diagnosis of lung adenocarcinoma after findings of lung nodule which was biopsied and showed primary lung adenocarcinoma. TTF-1 was also positive which is typically expressed by lung adenocarcinomas. Treatment for thyroid metastasis is surgery, along with treatment of primary malignancy. The earlier the diagnosis and treatment the more favorable the prognosis. Radiotherapy and chemotherapy are other means to reduce the recurrence. Thyroid hormone replacement will be warranted post operatively for hypothyroidism. We present this uncommon case to raise awareness about the presentation of thyroid metastasis to enhance timely diagnosis and intervention. Presentation: 6/1/2024

7550 Case Report On Concurrent Metastases To The Pituitary And Adrenal From A Primary Breast Cancer

Abstract Disclosure: M.V. David-santos: None. M.C. Isidro: None. Background: Metastatic Cancer to the pituitary gland is a rare condition accounting for 0.5% of all pituitary tumors. It rarely manifests clinically and is often found incidentally. Endocrine dysfunction usually arise, with 38.4% of cases presenting with Diabetes Insipidus, while 37.7% as Panhypopituitarism. On the other hand, prevalence of adrenal metastases is at 0.5 to 3.8% with 43% occurring bilaterally. Primary adrenal insufficiency occurs at 12.4% among those with bilateral metastases. Case: A 32-year old Chinese woman was diagnosed with Stage 4 breast adenocarcinoma ER PR Her2 Neu positive with metastases to the axillary lymph nodes, bone and right adrenal in July 2021. She underwent chemotherapy with Paclitaxel and Trastuzumab then radical mastectomy of the left breast in April 2022.5 months post op, PET scan was done which showed a 11 x 18 x 21 mm pituitary mass. In light of the primary malignancy, lesion was considered a metastatic focus. At that time, patient did not exhibit any neurologic symptoms such as blurring of vision or headaches. No polyuria, polydipsia, nocturia, easy fatigability, nausea or vomiting. Physical examination findings were normal. A hormonal panel showed the following: elevated Prolactin at 150 ng/ml (NV 3-20), normal plasma ACTH IRMA 10 pg/ml (NV &amp;lt; 50 pg/ml), low 8AM plasma cortisol at 1.55 ug/dL (Ref 5- 25 ug/dL), TSH was low at 0.15iIU/ml (0.27-3.75) while FT4 was normal at 0.87 ng/dl (NV 0.68 - 2.56).ACTH stimulation showed low cortisol at the 30th minute and 1st hour post ACTH infusion. Serum sodium and urine Osmolality were both normal. The hyperprolactinemia was attributed to Stalk effect, while the decreased cortisol was considered as central adrenal insufficiency. She was then started on Prednisone 5mg tab daily. Repeat TSH and FT4 5 months after showed normal TSH at 1.209, low FT4 at 5.97 pmol/L (NV 9.01-19.05). She was started on Levothyroxine 50mcg daily for the central hypothyroidism.Repeat Cranial MRI 4 months post diagnosis of the pituitary mass showed increased in its size. An endoscopic transsphenoidal resection and biopsy of the pituitary mass showed metastatic carcinoma of the pituitary gland. Staining of the sellar tumor were compatible with a metastatic carcinoma of breast origin. Intensity-modulated radiation therapy (IMRT) at 400 gray was done for 5 fractions and Trastuzumab was continued. Cranial MRI done 6 months post IMRT showed decreasing size of the pituitary mass to its latest size of 6 x 9 x 13 mm as of November 2023. Latest Whole abdominal CT scan of the adrenals showed clearing of the right adrenal Nodule. Conclusion: Breast cancer may also metastasize to endocrine organs causing hormonal dysfunction. Although curative treatment is no longer the goal for Metastatic breast cancer, prolongation of the quality of life is an important aspect to consider. Hormonal work up, surveillance and hormonal replacement can help in attaining this goal. Presentation: 6/3/2024

Imaging Features Differentiating Between Cardiac Sarcomas and Hematologic Neoplasms.

The aim of the study is to assess the efficacy of computed tomography (CT) and positron emission tomography (PET)/CT findings in differentiating between cardiac sarcoma and cardiac hematologic neoplasms, which are rare but potentially lethal primary cardiac malignancies. We searched the electronic medical record for pathology-proven cases from 2012 to 2023, finding 69 patients (46 sarcomas, 23 cardiac hematologic neoplasms). Imaging features including tumor size, atrioventricular (AV) groove involvement, right coronary artery (RCA) encasement by 180°, pericardial effusion, lymphadenopathy, and metabolic activity on fluorodeoxyglucose PET were reviewed by a radiology fellow. Statistical analysis was performed using Fisher exact test and Wilcoxon test. Cardiac sarcoma patients were younger (median age 49 years) compared to patients with cardiac hematologic malignancies (66 years, P = 0.006). While tumor size and chamber involvement were similar between the 2 categories, hematologic malignancies exhibited a notable predilection for AV groove involvement (70% vs 43%, P = 0.04) and RCA encasement (52% vs 26%, P = 0.02). Pulmonary metastases were more frequent in sarcoma cases (33% vs 4%, P = 0.006). There was no significant difference in fluorodeoxyglucose uptake. Lymphadenopathy was similar between the 2 disease groups. A decision tree constructed using AV groove involvement and patient age achieved 75% accuracy in predicting the diagnosis of the mass. Overall, there is a substantial overlap in imaging features of cardiac sarcomas and hematologic malignancies involving the heart. Involvement of the AV groove and RCA encasement can allow a radiologist to favor hematologic malignancy. Ultimately, biopsy is required to establish a diagnosis.

Anorectal melanoma: systematic review of the current literature of an aggressive type of melanoma.

Anorectal melanoma (ARM) is a rare malignancy often associated with a poor prognosis due to its late diagnosis and aggressive biological behavior. This review aims to comprehensively investigate ARM's diagnosis, management, and treatment, emphasizing its clinical characteristics, laboratory findings, and implications for patient prognosis. A systematic literature search was conducted in PubMed, Embase, and Cochrane CENTRAL databases from inception to 1 July 2024. This review synthesizes existing literature to provide a comprehensive understanding of this rare primary malignancy. A total of 110 articles reporting on 166 patients were included. Gender data were available for 131 cases, comprising 67 females (51.1%) and 64 males (48.9%). The median age was 66 years. The overall median time to diagnosis was 4 months for anal melanoma, 3 months for rectal melanoma, and 4 months for anorectal junction melanoma. The clinical presentation was nodular in 98.2% of cases. Pre-diagnosis symptoms included bleeding in 84.9% of cases, mucous elimination (6%), pain (68.7%), tenesmus (16.9%), and changes in bowel movements (28.5%). Overall survival (OS) was reported in 82 cases, with a median OS of 11 months: 11 months for anal melanoma, 7 months for rectal melanoma, and 12 months for anorectal junction melanoma. ARM is a rare and aggressive melanoma subtype often diagnosed at an advanced stage, leading to a poor prognosis. A female predominance was observed, consistent with other mucosal melanomas. Anal melanoma exhibited better progression-free survival, and OS compared to rectal and anorectal junction melanoma.

Impact of Age, Sex, and Stage on Risk of Developing Subsequent Primary Malignancies in Patients With Extramammary Paget's Disease: A Population-Based Study of the Surveillance, Epidemiology, and End Results Program.

Impact of Age, Sex, and Stage on Risk of Developing Subsequent Primary Malignancies in Patients With Extramammary Paget's Disease: A Population-Based Study of the Surveillance, Epidemiology, and End Results Program.

B-352 Effects of COVID-19 on Breast Cancer Positivity: A Retrospective and Predictive Study

Abstract Background The COVID-19 pandemic has had a significant impact on the healthcare system, resulting in overall reduction in access to healthcare services, including the suspension of screening programs and postponement of surgeries and medical treatments. The aim of this study was to evaluate the effects of the pandemic on breast cancer positivity from cases received at a laboratory in São Paulo, Brazil. Methods A retrospective analysis of a database from a pathology laboratory in São Paulo, Brazil, was performed during the 2017-2023 period and classified as following: pre-pandemic (January 2017-February 2020), pandemic (March 2020 - April-2022), and post-pandemic (May 2022-December 2023). Cases were classified as negative or positive for malignancies. Positive anatomopathological examinations (breast biopsies and surgical specimens) considered primary, metastatic mesenchymal or endothelial malignancies. The Mann-Kendall test was used to evaluate the trend, and the PACF (Partial Autocorrelation Function) correlogram was used to analyze historical memory for definition of the autoregressive model. The augmented Dickey-Fuller hypothesis test was applied to analyze whether the series is stationary or not, and the first differences test was applied. The ARIMA model was used for the estimates (1,1,1). Statistics were performed using the gretl software and pymannkendall library in the Python language. Results A total of 74,973 samples were evaluated during the 2017-2023 period. In the three-year pre-pandemic period, 32,644 tests were recorded, with an average of 29.34% positive cases. From the analysis of the pre-pandemic time series, there was a positive trend towards an increase in cases (p &amp;lt; 0.0001, z=6.1360, Tau=0.6955). In a non-pandemic scenario, from March 2020 to February 2021, the number of new tests expected would be 11,535; however, in the pandemic period, only 8,904 were observed, a 22.81% reduction on expected cases. According to the historical average positivity rate in the pre-pandemic period, the expected and observed total were, respectively, 3,384 and 2,566 positive cases for malignancy. Conclusions This study reveals a significant decrease of approximately 22.81% in new breast anatomopathological diagnoses during the COVID-19 pandemic in a laboratory in São Paulo, Brazil. For comparison purposes, we identified a 24.17% of missed opportunities on diagnoses of new malignancy-positive cases, compared to the pre-pandemic period. These findings highlight the need for strategies to mitigate the negative effects of the pandemic on the early detection and treatment of breast cancer.

The onset characteristics and prognosis of patients with radiation-associated second primary malignancy: a pancancer study in the US SEER cancer registries.

Cancer survivors have an elevated risk of developing a second primary malignancy (SPM) after radiation therapy (RT). Data on the association between RT and SPM are limited. Our aim was thus to investigate the impact of RT on the risk of developing SPMs and to evaluate the specific characteristics and prognostic outcomes. We enrolled a pancancer cohort using data from the Surveillance, Epidemiology, and End Results registries spanning from January 1973 to December 2015. Multivariable Cox and the Fine-Gray competing risk regression were employed to assess the hazard ratio (HR) and 95% confidence interval (CI) of SPMs in patients who received RT in comparison to those with no RT (NRT). Poisson regression was used to evaluate the RT-associated risks (RR) and the standardized incidence ratio (SIR) for SPMs. The analysis identified 24 types of risk-increased SPMs (RI-SPMs), including malignancies of the oropharynx, hypopharynx, larynx, esophagus, lung, breast, liver, pancreas, stomach, colon, rectum, ovary, corpus uteri, ureter, vagina, urinary bladder, penis, testis, and kidney, among others. The cumulative incidence of those with RI-SPMs was higher than that of the NRT patients (19.8% vs. 15.3%; P<0.001). The RR for RI-SPMs decreased with increasing age at FPM diagnosis (aged 20-49 years: RR 1.52; age 50-69 years: RR 1.31; age 70 years: RR 1.21), and the RR increased with longer latency period following FPM diagnosis (60-119 months: RR 1.28; 120-239 months: RR 1.24; 240-360 months: RR 1.46). The 10-year overall survival of those with RI-SPMs was significantly lower than that of the matched NRT patients (28.5% vs. 31.7%; P<0.001). Patients with RI-SPMs warrant greater attention given their time-cumulative onset risk and poor prognosis. Long-term surveillance is necessary for cancer survivors treated with RT.

Epidemiological Analysis of Cancer Patients Diagnosed With Cranial Metastasis at Initial Presentation

Introduction: Metastatic lesions are the most common brain tumors, comprising 52% of all cases. Early diagnosis is crucial to improve patient outcomes, but many cases remain undiagnosed until advanced stages. This study aimed to investigate the characteristics of patients diagnosed with brain metastasis concurrently with their primary malignancy, examine prognostic factors, and compare these findings with brain metastases of known primary origins. Method: A retrospective analysis was conducted on 184 patients between 18-80 years diagnosed with brain tumors between January 2018 and January 2019. Patient data were collected from clinical records, and statistical analyses were performed using SPSS 26.0. Results: Out of the total patients, 43% were diagnosed brain metastases. Among these, 33% had no known primary malignancy at diagnosis. In this group, 92.3% were over 50 years old, and 77% were male. The most frequent primary cancer was lung cancer (81%). Males had an average time to metastasis diagnosis approximately twice as long as females. A higher incidence of metastasis correlated with a lower Karnofsky Performance Score, indicating reduced operability and quality of life. Conclusion: Early diagnosis is critical to improving outcomes. Routine cranial imaging for patients over 50 may aid in early intervention.

The genetically predicted causal associations between circulating 3-hydroxybutyrate levels and malignant neoplasms: A pan-cancer Mendelian randomization study

The ketogenic diet or exogenous supplementation with 3-hydroxybutyrate (3HB) is progressively gaining recognition as a valuable therapeutic or health intervention strategy. However, the effects of 3HB on cancers have been inconsistent in previous studies. This study aimed to comprehensively investigate the causal effects of circulating 3HB levels on 120 cancer phenotypes, and explore the 3HB mediation effect between liver fat accumulation and cancers. Univariate Mendelian randomization (UVMR) was used in this study to investigate the causal impact of circulating 3HB levels on cancers. We conducted meta-analyses for 3HB-cancer associations sourced from different exposure data. In multivariate MR(MVMR), the body mass index, alcohol frequency and diabetes were included as covariates to investigate the independent effect of 3HB on cancer risk. Additionally, utilizing mediation MR analysis, we checked the potential mediating role of 3HB in the association between liver fat and cancer. Integrating findings from UVMR and MVMR, we observed that elevated circulating 3HB levels were associated with reduced risk of developing diffuse large B-cell lymphoma(DLBCL) (OR[95%CI]=0.28[0.14-0.57] p=3.92e-04), biliary malignancies (OR[95%CI]=0.30[0.15-0.60], p=7.67e-04), hepatocellular carcinoma(HCC) (OR[95%CI]=0.25[0.09-0.71], p=9.33e-03), primary lymphoid and hematopoietic malignancies (OR[95%CI]=0.76[0.58-0.99], p=0.045). Further UVMR analysis revealed that an increase in the percent liver fat was associated with reduced 3HB levels (Beta[95%CI]=-0.073[-0.122∼-0.024], p=0.0034) and enhanced susceptibility to HCC (OR[95%CI]=13.9[9.76-19.79], p=3.14e-48), biliary malignancies (OR[95%CI]=4.04[3.22-5.07], p=1.64e-33), nasopharyngeal cancer (OR[95%CI]=3.26[1.10-9.67], p=0.03), and primary lymphoid and hematopoietic malignancies (OR[95%CI]=1.27[1.13-1.44], p=1.04e-4). Furthermore, 3HB fully mediated the effect of liver fat on susceptibility to DLBCL (OR[95%CI]=1.076[1.01-1.15], p=0.034). Circulating 3HB is associated with a reduced susceptibility to developing DLBCL, HCC, biliary malignancies, and primary lymphoid and hematopoietic malignancies. The impaired ketogenesis induced by metabolic-dysfunction associated fatty liver disease (MAFLD) contributes to risk of DLBCL.

S2854 An Unlikely Etiology of Colon Masses in a Patient With Three Known Primary Malignancies

S2854 An Unlikely Etiology of Colon Masses in a Patient With Three Known Primary Malignancies