High Local Recurrence Rate Research Articles

Integrated Care in Specialized Networks: Leveraging Early Referrals to Reduce Local Recurrence in Soft Tissue Sarcoma

This study evaluated the impact of care pathways on the incidence of local recurrence (LR) in patients with soft tissue sarcomas (STS) and identified factors predictive of LR. It compared outcomes between patients managed entirely within a comprehensive care pathway (CCP) at the Swiss Sarcoma Network (SSN) and those who experienced fragmented care pathways (FCPs), where initial treatment occurred outside specialized centers. This prospective study utilized real-world-time data from the SSN-Sarconnector, capturing quality indicators through weekly Multidisciplinary Team/Sarcoma-Board (MDT/SB) meetings. The overall incidence of LR was 17.6% (n = 68/386), higher than rates typically reported in sarcoma center-based studies due to the inclusion of patients with prior inadequate management from real-world referrals. In a univariable logistic regression analysis, the FCP was significantly associated with higher LR rates, unplanned “whoops” resections (25.4%, n = 96), and positive surgical margins, emphasizing the detrimental impact of suboptimal initial management outside of specialized centers. Multivariable analysis confirmed that the FCP (aOR 2.7, 95% CI [1.41, 5.12], p = 0.003), tumor size (aOR 1.49, 95% CI [1.1, 2.02], p = 0.01), and biological behavior (aOR 5.84 95% CI [1.8, 18.86], p = 0.0003) are independent predictors of LR. Notably, patients referred to sarcoma centers after an initial FCP presented with inadequately managed disease, such as incomplete resections and unplanned surgeries, leading to increased complexity of subsequent treatments. These findings underscore the critical role of referral patterns on sarcoma center outcomes, highlighting the significant disparity in LR rates between institutions. The need for improved education and standardized early referral strategies at the spoke level is paramount to optimize patient outcomes and reduce the burden of LR. Enhanced spoke-level education and standardized referral protocols are critical to ensuring effective initial management and optimizing patient outcomes within specialized sarcoma networks like the SSN.

Non-invasive miRNAs for early detection and diagnosis of lacrimal adenoid cystic carcinoma.

Lacrimal adenoid cystic carcinoma (LACC) is one of the most common malignant epithelial tumors of the lacrimal gland, characterized by high rates of local recurrence, distant metastases, and tumor-related mortality. This malignancy impairs the lacrimal gland's ability to secret tears, thereby disrupting the normal function of the ocular surface. Due to ineffective diagnostic approaches and the complex anatomical location of the lacrimal gland within the orbit, many LACC patients are often diagnosed at the later stages. Therefore, it is urgent to develop a simple and convenient method for early detection of LACC through biomarker analysis by liquid biopsies, such as blood or tears. Various microRNAs (miRNAs) derived from liquid biopsies have been shown to serve as biomarkers for early diagnosis of tumors. In the present study, we screened LACC-specific miRNAs using miRNA microarray analysis in both primary and recurrent patient groups. We then validate their expression by qPCR experiments conducted in tissues, cell lines, tear fluid and serum to explore the association between these miRNAs and LACC development and prognosis. Our findings reveal that hsa-miR-200b-3p, hsa-miR-200c-3p and hsa-miR-141-3p are significantly upregulated in LACC, and the microarray data showed that these three miRNAs were significantly elevated in the recurrence group compared to the primary group. In conclusion, detecting miRNA expression in tear fluid and serum provides non-invasive biomarkers for the early diagnosis of LACC and may facilitate monitoring outcomes related to lacrimal gland diseases.

Small particle drug-eluting beads-transarterial chemoembolization combined with targeted therapy in the clinical treatment of unresectable liver cancer.

Liver cancer is a highly malignant tumor with significant clinical impact. Chemotherapy alone often yields suboptimal outcomes in both the short and long term, characterized by high rates of local recurrence and distant metastasis, leading to a poor long-term prognosis. To evaluate the clinical efficacy of small particle drug-eluting beads-transarterial chemoembolization (DEB-TACE) combined with targeted therapy for the treatment of unresectable liver cancer. We analyzed clinical data from 74 patients with unresectable liver cancer admitted between January 2019 and December 2020. Based on the different treatment regimens administered, patients were divided into the control (36 patients receiving sorafenib alone) and joint (38 patients receiving small particle DEB-TACE combined with sorafenib) groups. We compared liver function indicators [alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), albumin (ALB)] and serum tumor markers [alpha fetoprotein (AFP)] before and after treatment in both groups. Short-term efficacy measures [complete response (CR), partial response, progression disease, stable disease, objective response rate (ORR), and disease control rate (DCR)] were assessed post-treatment. Long-term follow-up evaluated median overall survival (OS), progression-free survival (PFS), and adverse reaction rates between the two groups. One month post-treatment, the joint group demonstrated significantly higher rates of CR, ORR, and DCR compared to the control group (P < 0.05). Three days after treatment, the joint group showed elevated levels of ALT, AST, and TBIL but reduced levels of ALB and AFP compared to the control group (P < 0.05). The median OS was 18 months for the control group and 25 months for the joint group, while the median PFS was 15 months for the control group and 22 months for the joint group, with significant differences observed (log-rank: χ 2 = 7.824, 6.861, respectively; P = 0.005, 0.009, respectively). The incidence of adverse reactions was not significantly different between the groups (P > 0.05). The combination of small particle DEB-TACE and sorafenib significantly improves both short- and long-term outcomes in the treatment of unresectable liver cancer while preserving liver function.

ANALYSING THE RATE OF RECURRENCE AND LEPTOMENINGEAL DISEASE IN POSTERIOR FOSSA BRAIN METASTASES FOLLOWING POSTOPERATIVE RADIOTHERAPY- SINGLE CENTRE EXPERIENCE

Abstract AIMS The management of posterior fossa brain metastases is complex and necessitates a multidisciplinary approach involving neurosurgeons and oncologists. Post-operative radiotherapy (PORT) to surgical cavity has demonstrated positive oncologic outcomes as well as preserving cognitive function when compared to conventional whole brain radiation therapy. However, larger post-operative volumes in posterior fossa and greater target volume uncertainty due to presence of pseudomeningocele may result in an increased risk of local recurrence (LR) and leptomeningeal disease (LMD). The aim of this retrospective single centre study was to determine the rates of LR and LMD in patients with posterior fossa metastases who underwent PORT to surgical cavity. METHOD Retrospective analysis of data of patient who underwent PORT in between 2017-2022, for posterior fossa brain metastases at our centre. Clinical, imaging and radiotherapy data was collected from electronic medical records. Statistical analysis was performed using SPSS Statistics version 28.0.1. RESULTS We identified 42 patients meeting the study criteria. The median age of the patients was 60.5 years. 71.4% of patients were females, while 28.6% were males. 52.4% of patients had pseudomeningocoele on their radiotherapy planning scans. The median time gap between the date of surgery and initiation of radiotherapy was 34.5 days. 20 out of 42 (47.6%) patients had local recurrence of a posterior fossa brain metastasis and 7 out of 42 (16.7%) patients developed LMD. Out of 7 patients with LMD, 4 patients had pseudomeningocoele present at the time of PORT. The timing of radiotherapy after surgery (≤4 weeks or &amp;gt;4 weeks) showed no statistically significant impact on LR (p-value: 0.413, log-rank test). CONCLUSION The risk of LR remains high despite PORT. This study highlights the challenges in management of posterior fossa metastases. High LR and LMD rates underscore the need for improved treatment strategies.

Postoperative pathological findings and prognosis of early laryngeal and pharyngeal cancer treated with transoral surgery

ObjectiveTransoral surgery for early-stage pharyngeal and laryngeal cancer provides good local control and is less invasive than external incisions. Postoperative pathological findings are considered the most important indicators for determining postoperative treatment, but detailed criteria have not been established. In this study, we evaluated the impact of postoperative pathological findings on prognosis of patients undergoing transoral surgery. MethodsThis study included patients with oropharyngeal, hypopharyngeal, and supraglottic cancer who underwent transoral surgery at Gifu University Hospital from April 2016 to December 2023. Resection margins were pathologically evaluated with horizontal and vertical margins, and vascular invasion was evaluated in three categories: lymphatic invasion, venous invasion, and perineural invasion. The correlation between each postoperative pathological finding and prognosis was evaluated. ResultsA total of 70 cases were assessed in this study. Cases of horizontal margin positive were 38.6 %, and cases of vertical margin positive were 27.1 %. Prognoses were comparable to previous reports. Despite the high margin positive rate, the 5-year overall survival rate was 77.1 %. The 5-year disease-specific survival rate was 89.7 %, and the 5-year local control rate was 85.3 %. Notably, when evaluated by margin direction, cases with positive horizontal margins had significantly worse prognoses. Although no significant correlation was found between vascular invasion and prognosis, cases of venous invasion tended to have a higher local recurrence rate. ConclusionThis study suggests that transoral surgery has good prognosis despite a high positive-margin rate. However, detailed criteria for additional treatment have not been developed, and further case accumulation is required. Intriguingly, positive horizontal margins are correlated with significantly worse prognosis. This result may be related to a high risk of multiple cancers, and careful follow-up after surgery is recommended.

Planned and Unplanned Sarcoma Resections: Comparative Analysis of Local Recurrence, Metastasis, and Mortality

Background: Sarcomas, a diverse group of malignant tumors arising from mesenchymal tissues, pose significant diagnostic and therapeutic challenges. This study compares the outcomes of planned resections (PEs) and unplanned resections (UEs) to inform better clinical practices. Methods: Data were analyzed from the Swiss Sarcoma Network (SSN), including patients with soft tissue and bone sarcomas treated at two major hospitals. This study utilized logistic regression and Cox regression models to examine the odds of UEs and their impact on local recurrence-free survival. Results: Among 429 patients registered by SSN members, 323 (75%) underwent PEs and 106 (25%) experienced UEs. PEs were associated with significantly larger tumors (94 mm vs. 47 mm, p &lt; 0.001) and higher-grade tumors (Grade 3: 50.5% vs. 37.4%, p = 0.03). Despite achieving superior resection margins (R0: 78.8% vs. 12.6%, p &lt; 0.001), PEs showed higher metastasis rates at follow-up (31.0% vs. 10.4%, p &lt; 0.001) and greater cancer-specific mortality (16.7% vs. 6.6%, p = 0.01). UEs, while linked to higher local recurrence, did not significantly affect metastasis-free survival (MFS) or overall survival (OS). Conclusions: PEs achieve superior immediate surgical outcomes but are linked to higher metastasis and cancer-specific mortality due to the advanced stage of tumors. UEs, while associated with higher local recurrence rates, do not significantly impact MFS or OS. Early detection, comprehensive diagnostics, and timely referrals to specialized sarcoma hubs are essential to avoid UEs and reduce metastatic risk. Future research should focus on developing diagnostic tools using individual tumor and patient characteristics to improve sarcoma management.

Racial and Ethnic Differences in Patient Presentation and Treatments in Head and Neck Dermatofibrosarcoma Protuberans

AbstractHead and neck dermatofibrosarcoma protuberans (HNDFSP) is a rare neoplasm with a high rate of local infiltration and local recurrence but a low rate of distant metastasis. Given the limited literature on HNDFSP and existing studies pointing to possible racial and ethnic differences, further research is needed to understand important clinical correlates that may impact treatment and prognosis. The National Cancer Database (NCDB) was queried for all cases of HNDFSP diagnosed from 2004 to 2016. Demographic characteristics of the included patients were compared using chi-squared and t-tests. Kaplan-Meier and Cox multivariable regression analyses were performed to assess survival differences. Of the 778 included patients, 526 (67.6%) patients were white, 113 (14.5%) were black, 33 (4.2%) were Asian, 87 (11.2%) were Hispanic, and 19 (2.4%) were classified as Other. White patients presented at a significantly older age (43.8 years) than did black (38.9 years) and Hispanic patients (37.9 years) (p = 0.02). White patients with HNDFSP had significantly higher income status (p = 0.0001), were more likely to be insured (p = 0.0001), and were more likely to have a high school diploma (p = 0.0001). There were no significant racial differences in 5-year (96.1%) or 10-year (92.0%) overall survival. None of the variables yielded a statistically significant value in Cox analysis. Differences exist in HNDFSP presentation between racial groups. Specifically, differences in income, insurance status, education level, and age of presentation exist between these groups. Future studies focused on morbidity are needed to better understand the consequences of these difference on HNDFSP patients.

Rare Intravascular Involvement of Pleomorphic Dermal Sarcoma Seen During Mohs Micrographic Surgery.

Pleomorphic dermal sarcoma (PDS) and atypical fibroxanthoma (AFX) are rare mesenchymal tumors that share similar clinical, histological, and immunohistochemical characteristics. Careful histopathological examination of a biopsy specimen that includes subcutaneous fat remains the preferred way to differentiate between these tumors. AFX is limited to dermal invasion, whereas PDS demonstrates deeper invasion. Moreover, PDS may present with tumor necrosis and high-grade histological findings, such as lymphovascular and perineural invasion, features absent in AFX. However, like PDS, AFX is a diagnosis of exclusion, and an exhaustive immunohistochemistry panel is recommended to distinguish these tumors from other spindled cell tumors in the differential diagnosis. The authors present the case of an 86-year-old man with biopsy-suspected AFX who was referred for Mohs micrographic surgery for tumor excision. During Mohs, the tumor was observed to have invaded deeply into the subcutaneous tissue and galeal aponeurosis, aligning more closely with a PDS. The diagnosis of PDS was confirmed using en face processing during Mohs surgery, which captured the intravascular involvement of a solitary vessel. Differentiating between PDS and AFX is important because PDS is a more aggressive tumor, with a higher rate of local recurrence and metastasis, and requires closer monitoring.

Muscle metastasis from cervical chordoma: a case report.

Chordomas are rare primary bone tumours that commonly occur in the sacrococcygeal and skull base region and have high rates of local recurrence. They have a locally aggressive course and the most common site of distant metastasis is the lung. The aim of this case report is to present the imaging findings of instance of muscle metastasis, a rare occurrence in cervical chordoma.

Outcomes following extended resection of radiation-induced angiosarcoma of the breast: a sarcoma unit experience and systematic review.

Radiation-induced angiosarcoma (RIAS) of the breast is a rare tumour with high rate of local recurrence. The aim of this study is to evaluate the outcome of radical resections. A retrospective analysis of all patients who underwent extended surgical resection for RIAS of the breast between 2013 and 2022. Included were patients who underwent radical resection, including complete resection of previously irradiated skin and underlying fascia of pectoralis major. Post-operative and long-term oncological outcomes were than analysed. A systematic review was performed using the MEDLINE database in the last 20 years. Twenty-two (n = 22) patients met the inclusion criteria. The median length of the specimen was 220 mm (range, 120-377 mm). At a median follow-up of 33.5 months (range, 7.9-102.4), 3 (13.6%) patients had both local and metastatic lung disease and 1 (4%) patient with only lung metastasis. The estimated 3- and 5-year OS was 81.1% and 57.9%, respectively. The estimated 3- and 5-year DSS was 91.7% and 65.5%, respectively. The estimated 3- and 5-year DFS rate were both 75.2%. The systematic review identified 17 studies with a recurrence rate ranging from 33% to 100%. Treatment of RIAS of the breast with an up-front locally extended approach is associated with a low rate of local recurrence compared with the reported literature.

Incremental high power radiofrequency ablation with multi-electrodes for small hepatocellular carcinoma: a prospective study

Radiofrequency ablation (RFA) offers a minimally invasive treatment for small hepatocellular carcinoma (HCC), but it faces challenges such as high local recurrence rates. This prospective study, conducted from January 2020 to July 2022, evaluated a novel approach using a three-channel, dual radiofrequency (RF) generator with separable clustered electrodes to improve RFA’s efficacy and safety. The study employed a high-power, gradual, stepwise RFA method on HCCs (≤ 4 cm), utilizing real-time ultrasound-computed tomography (CT)/magnetic resonance imaging (MRI) fusion imaging. Involving 110 participants with 116 HCCs, the study reported no major complications. Local tumor progression (LTP) and intrahepatic remote recurrence (IRR) rates were low, with promising cumulative incidences at 1, 2, and 3 years for LTP (0.9%, 3.6%, 7.0%) and IRR (13.9%, 20.5%, 31.4%). Recurrence-free survival (RFS) rates were similarly encouraging: LTP (99.1%, 96.4%, 93.0%) and IRR (86.1%, 79.5%, 68.6%). This innovative gradual, incremental high-power RFA technique, featuring a dual switching monopolar mode and three electrodes, represents an effective and safer management option for small HCCs.Trial registrationclinicaltrial.gov identifier: NCT05397860, first registered on 26/05/2022.

Perioperative, functional and oncologic outcomes of percutaneous ablation versus minimally invasive partial nephrectomy for clinical T1 renal tumors: outcomes from a pooled analysis.

The objective of this study was to perform a comprehensive pooled analysis aimed at comparing the efficacy and safety of percutaneous ablation (PCA) versus minimally invasive partial nephrectomy (MIPN), including robotic and laparoscopic approaches, in patients diagnosed with cT1 renal tumors. We conducted a comprehensive search across four major electronic databases: PubMed, Embase, Web of Science, and the Cochrane Library, targeting studies published in English up to April 2024. The primary outcomes evaluated in this analysis included perioperative outcomes, functional outcomes, and oncological outcomes. A total of 2449 patients across 17 studies were included in the analysis. PCA demonstrated superior outcomes compared to MIPN in terms of shorter hospital stays (WMD: -2.13days; 95% Confidence Interval [CI]: -3.29, -0.97; p = 0.0003), reduced operative times (WMD: -109.99min; 95% CI: -141.40, -78.59; p < 0.00001), and lower overall complication rates (OR: 0.54; 95% CI: 0.40, 0.74; p = 0.0001). However, PCA was associated with a higher rate of local recurrence when compared to MIPN (OR: 3.81; 95% CI: 2.45, 5.92; p < 0.00001). Additionally, no significant differences were observed in major complications, estimated glomerular filtration rate decline, creatinine variation, overall survival, recurrence-free survival, and disease-free survival between the two treatment modalities. PCA presents a notable disadvantage regarding local recurrence rates in comparison to MIPN. However, PCA offers several advantages over MIPN, including shorter durations of hospital stay, reduced operative times, and lower complication rates, while achieving similar outcomes in other oncologic metrics.

Musculoskeletal glomus tumor: a review of 218 lesions in 176 patients.

To review the spectrum of clinical and imaging features of glomus tumor involving the musculoskeletal system including the typically solitary forms as well as the rarer multifocal forms (glomuvenous malformation and glomangiomatosis). A retrospective review of our institutional pathology database from 1996 to 2023 identified 176 patients with 218 confirmed glomus tumors. Primary imaging studies included MRI (125), radiographs (100), clinical/intraoperative photos (77), and ultrasound (36). Lesions were divided into two groups: those that are typically solitary involving specific anatomic areas (finger, toe, soft tissue, coccyx, and bone), and those that are multifocal (glomuvenous malformation and glomangiomatosis). The finger was the most frequently involved anatomic location for the classic (sporadic) glomus tumor occurring in 51% of patients, 77% of which were women, with the nail plate involved in more of the 75% of cases. Sporadic lesions involving the skin, subcutaneous adipose tissue, and deep soft tissue were termed "soft tissue," and were identified in 39% of patients, 90% of which were in the extremities and in men in 81% of cases. The multifocal syndromic forms of glomus disease occurred in younger individuals and involved less than 6% of the study group. Patients with glomuvenous malformation presented early with predominantly cutaneous involvement, while those with glomangiomatosis present later, often with both superficial and deep involvement, and a high rate of local tumor recurrence. While glomus tumor is generally uncommon, it frequently involves the musculoskeletal extremities. Knowledge of the spectrum of characteristic locations and appearances will facilitate definitive diagnosis.

Fibrosarcomatous Transformation in Dermatofibrosarcoma Protuberans of the Male Breast and its Association with Magnetic Resonance Imaging and Immunohistopathologic Features.

Dermatofibrosarcoma Protuberans (DFSP) is a rare soft tissue sarcoma, accounting for approximately 1% of all tumors; however, DFSP of the breast is extremely rare. Moreover, DFSP generally has a low malignant potential and is characterized by a high rate of local recurrence along with a small but definite risk of metastasis. The risk of metastasis is higher in fibrosarcomatous transformation in DFSP than in ordinary DFSP. We have, herein, reported a case of a 61-year-old male patient with fibrosarcomatous transformation in DFSP. Preoperative Dynamic Contrastenhanced Magnetic Resonance Imaging (DCE-MRI) of the breast revealed an oval-shaped mass with heterogeneous internal enhancement, a large vessel embedded within, and a washout curve pattern on kinetic curve analysis. The mass exhibited a hyperintense signal on Diffusion-weighted Imaging (DWI), with a low apparent diffusion coefficient value. Histologically, the bland spindle tumor cells were arranged in a storiform pattern. Areas with the highest histological grade demonstrated increased cellularity, cytological atypia, and mitotic activity. Immunohistochemically, Ki-67 and p53 were highly expressed. Recognizing the risk and accurately diagnosing fibrosarcomatous transformation in male breast DFSP are critical for improving prognosis and establishing appropriate treatment and follow-up plans. This emphasizes the significance of combining immunohistopathological features with DCE-MRI and DWI to assist clinicians in the early and accurate diagnosis of sarcomas arising from male breast DFSP.

Myxoinflammatory fibroblastic sarcoma of the liver: Case report and literature review.

Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare low-grade malignant soft tissue sarcoma that primarily affects the distal extremities in adults, with the highest incidence in patients in their 40s and 50s. It has a high local recurrence rate and a low metastasis rate. Although MIFSs have been documented in other sites, an MIFS in the liver is highly unusual. Herein, we present a case of a patient with hepatic MIFS. The patient was a 58-year-old Chinese man with abdominal pain as the primary symptom. Abdominal computed tomography and magnetic resonance imaging revealed a mass in the right posterior lobe of the liver. The patient underwent surgical excision, and the excised specimen was identified as MIFS. Three years later, the patient returned to our hospital for abdominal pain. Computed tomography and magnetic resonance imaging revealed a mass in liver segments 2/3/4. Postoperative pathological examination of the tumor revealed the recurrence of MIFS. The patient underwent surgical resection of the MIFS. The patient received multiple pirarubicin-based chemotherapy treatments and an ALK inhibitor (anlotinib) within 6 months after surgery, but the tumor recurred. MIFS can not only occur in the proximal limbs, trunk, head, and neck but can also affect the abdominal organs. Surgical resection remains the primary treatment option for MIFS in the absence of any contraindications. Because the recurrence rate of MIFS is high, meticulous long-term monitoring is required.

Percutaneous liver-directed therapies of intrahepatic cholangiocarcinoma.

Cholangiocarcinoma is a hepatobiliary malignancy which can manifest anywhere along the biliary tree. Intrahepatic cholangiocarcinoma occurs in the liver within or beyond the second order bile ducts. The prognosis for patients with intrahepatic cholangiocarcinoma is poor, even when successfully resected there is a very high rate of local recurrence. The available systemic therapies are currently limited and have high rates of toxicity. Percutaneous and transarterial liver-directed therapies can be used to treat intrahepatic cholangiocarcinoma with results comparable to current standard of care systemic therapies in some circumstances. This manuscript will review these the techniques and efficacy of percutaneous and transarterial liver-directed therapies for intrahepatic cholangiocarcinoma.

MDB-02. RECURRNET SPINAL DESMOID FIBROMATOSIS IN A CHILD WITH APC GERMLINE MUTATION-RELATED MEDULLOBLASTOMA

Abstract BACKGROUND Familial adenomatous polyposis (FAP) is an autosomal-dominant dominant Familial Cancer Syndrome FCs Caused by Germline inactivation of adenomatous polyposis coli (APC) tumor suppressor gene, results in up-regulation of the WNT signaling pathway which increases the risk of colorectal cancer CRC, colon polyposis and extracolonic tumors like gastric and duodenal carcinomas WNT-activated Medulloblastoma MBL and Desmoid fibromatosis (DF) DF are locally aggressive soft tissue tumors with high local recurrence rates after Surgical excision role of adjuvant chemotherapy or Radiotherapy is still unclear. METHODS A 6-year-old boy product of non-consanguineous marriage with positive family HX brain tumor Diagnosed with Non-Metastatic Average Risk MBL WHO grade IV classic histology, he had craniotomy and Gross tumor resection followed by craniospinal irradiation at 23.4 Gy, plus a boost to posterior fossa/tumor bed up to 54 Gy, followed by 8 maintenance chemotherapy cycles as HIT-MED protocol Cisplatin/VCR/CCNU total. 3 years post end of therapy the pateint was in complete remission from MBL when routing MRI surveillance showed a new left paravertebral muscle lesion within the irradiation field from T1 to T4 levels which progressed gradually over a short follow-up time he had surgical resection of the tumor with Pathological diagnosis of Desmoid fibromatosis. after six months he had a second recurrence of the spinal tumor that needed a second surgical resection. Result: positive Genetic testing for Germline pathogenic mutation of APC gene exons 7 to 16 confirmed the diagnosis of autosomal familial adenomatous polyposis type 1(FAP1). Up to date, he is stable on endoscopic and MRI surveillance with radiological evidence of slow progression of the paraspinal tumor CONCLUSION Medulloblastomas associated with APC germline mutation have favorable outcomes that may need de-escalating therapeutic protocol with reduced intensity craniospinal irradiation aiming to reduce the incidence of secondary tumors after adjuvant treatment for MBL

A durable response to gemcitabine monotherapy in metastatic cardiac angiosarcoma

Introduction: Primary cardiac angiosarcoma is a rare neoplasm with high rates of local recurrence and distant metastasis for which optimum treatment is poorly defined. Case Report: We present the case of a 49-year-old man with cardiac angiosarcoma with distant metastases who exhibits durable response to gemcitabine monotherapy. At initial diagnosis, he underwent complete resection with adjuvant Adriamycin and Ifosfamide for four cycles as well as external beam radiation for possible residual disease. He had recurrence with liver and bone metastases four years later. He received Gemcitabine and Docetaxel for six cycles followed by Gemcitabine monotherapy with no evidence of recurrence for the next three years. Conclusion: This patient’s consistent response to gemcitabine maintenance therapy in metastatic cardiac angiosarcoma adds to relative paucity of data regarding the management of this rare malignancy, offering insight into best practice and hope for patients afflicted with this disease.

Ipsilateral recurrence and breast cancer outcomes in carriers of BRCA1/2 pathogenic variants according to locoregional treatments.

e12584 Background: Our previous study of 255 breast cancer (BC) patients, carriers of BRCA1/2 pathogenic variants (PV), showed that patients who underwent mastectomy without post-mastectomy radiotherapy (PMRT) had higher rates of local recurrence (LR) than those who underwent PMRT or breast-conserving therapy (BCT). Our aim was to verify our previous findings in a larger cohort. Methods: Clinical data was extracted from the medical records of BRCA1/2 mutation carriers with BC, treated at a single institution between 1/2006-12/2022. Data extracted included demographics, tumor characteristics, disease stage, surgical and oncological treatment, use of RT and disease outcomes. Results: Overall, 481 BC patients with BRCA1/2 germline mutations were identified, 20 of them presented with synchronous bilateral disease. Median follow-up time was 75.3 months (range 12.5-211). After excluding 16 patients with metastatic de novo disease and 1 patient not operated for medical reasons, 464 patients with 484 primary tumors were analyzed. Of these, 234 (48.3%) mastectomies (84% were skin- or nipple-sparing, SSM/NSM, 16% total mastectomy) and 250 (51.7%) BCT were performed. In the non-PMRT group (n=153) there was earlier disease stage at diagnosis (77.6% of tumors were Tis and T1N0) compared to the PMRT group (n=81) and BCT group (4.9% and 45%, respectively, p&lt;0.001). All had free surgical margins. LR rate in the study cohorts was 20/153 breasts (13.1%) in the non-PMRT group compared with 1/81 breasts (1.2%) in the PMRT group (p=0.003), and 16/250 (6.4%) in the BCS group (p=0.024). All but one recurrence were invasive. Cumulative incidence of LR at 5 and 10 years was 14.1% and 15.9% in the non-PMRT, compared to 4.4% and 9.4% in BCT group, respectively (p=0.034). No significant difference in overall survival was observed (p=0.39). Conclusions: BRCA1/2 PV carriers treated with mastectomy without PMRT had higher rates of LR than those who underwent mastectomy and PMRT or BCT, despite earlier stage disease. Further studies are needed to compare these outcomes to non- BRCA1/2 carriers and find means to improve local control in these patients.

P53 as a Potential Actionable Target in Myxofibrosarcoma: A Molecular and Pathologic Review of a Single-Institute Series

Myxofibrosarcoma (MFS) is a common adult soft tissue sarcoma characterized by high-local recurrence rate, poorly understood molecular pathogenesis, lack of specific prognostic markers, and effective targeted therapies. To gain further insights into the disease, we analyzed a well-defined group of 133 primary MFS cases. Immunohistochemical (IHC) staining for p53, MET, RET, and RB was performed. Twenty-five cases were analyzed by targeted resequencing of known cancer driver hotspot mutations, whereas 66 and 64 MFSs were examined for the presence of genetic variants in TP53 and MET gene, respectively. All clinical, histologic, immunostaining, and genetic variables were analyzed for their impact on 5-years overall survival (OS) and 5-years event-free survival (EFS). In our series, no grade I tumors relapsed and high grade are related to a positive MET immunostaining (P = .034). Both local recurrence (P = .038) and distal metastases (P = .016) correlated to the presence of “single nucleotide variant (SNV) plus copy number variation (CNV)” in TP53. Multivariate analysis revealed that age (>60 years), metastasis at presentation, and positive IHC-p53 signal are risk factors for a poor OS (P = .003, P = .000, and P = .002), whereas age (>60 years), synchronous metastasis, and tumor size (>10 cm) predict an unfavorable 5-years EFS (P = .011, P = .000, and P = .023). Considering the smaller series (n = 66) that underwent molecular screening, the presence of “SNV+CNV” in TP53 represents a risk factor for a worse 5-years EFS (hazard ratio, 2.5; P = .017). The present series confirms that TP53 is frequently altered in MFS (86.4% of cases), appearing to play an important role in MFS tumorigenesis and being a potentially drugable target. A positive p53 immunostainings is related to a poor diagnosis, and it is the presence of a single nucleotide genetic alterations in TP53 that is essential in conferring MFS an aggressive phenotype, thus supporting the use of molecular profiling in MFS to better define the role of p53 as a prognostic factor.