High Local Recurrence Research Articles

Necrotic related-lncRNAs: Prediction of prognosis and differentiation between cold and hot tumors in head and neck squamous cell carcinoma.

Treatment of head and neck squamous cell carcinoma (HNSCC) is a substantial clinical challenge due to the high local recurrence rate and chemotherapeutic resistance. This project seeks to identify new potential biomarkers of prognosis prediction and precision medicine to improve this condition. A synthetic data matrix for RNA transcriptome datasets and relevant clinical information on HNSCC and normal tissues was downloaded from the Genotypic Tissue Expression Project and The Cancer Genome Atlas (TCGA). The necrosis-associated long-chain noncoding RNAs (lncRNAs) were identified by Pearson correlation analysis. Then 8-necrotic-lncRNA models in the training, testing and entire sets were established through univariate Cox (uni-Cox) regression and Lasso-Cox regression. Finally, the prognostic ability of the 8-necrotic-lncRNA model was evaluated via survival analysis, nomogram, Cox regression, clinicopathological correlation analysis, and receiver operating characteristic (ROC) curve. Gene enrichment analysis, principal component analysis, immune analysis and prediction of risk group semi-maximum inhibitory concentration (IC50) were also conducted. Correlations between characteristic risk score and immune cell infiltration, immune checkpoint molecules, somatic gene mutations, and anti-cancer drug sensitivity were analyzed. Eight necrosis-associated lncRNAs (AC099850.3, AC243829.2, AL139095.4, SAP30L-AS1, C5orf66-AS1, LIN02084, LIN00996, MIR4435-2HG) were developed to improve the prognosis prediction of HNSCC patients. The risk score distribution, survival status, survival time, and relevant expression standards of these lncRNAs were compared between low- and high-risk groups in the training, testing and entire sets. Kaplan-Meier analysis showed the low-risk patients had significantly better prognosis. The ROC curves revealed the model had an acceptable predictive value in the TCGA training and testing sets. Cox regression and stratified survival analysis indicated that the 8 necrosis-associated lncRNAs were risk factors independent of various clinical parameters. We recombined the patients into 2 clusters through Consensus ClusterPlus R package according to the expressions of necrotic lncRNAs. Significant differences were found in immune cell infiltration, immune checkpoint molecules, and IC50 between clusters, suggesting these characteristics can be used to evaluate the clinical efficacy of chemotherapy and immunotherapy. This risk model may serve as a prognostic signature and provide clues for individualized immunotherapy for HNSCC patients.

Magnetic resonance imaging for prospective assessment of local recurrence of non-small cell lung cancer after stereotactic body radiation therapy

ObjectivesTo evaluate multi-parametric MRI for distinguishing stereotactic body radiation therapy (SBRT) induced pulmonary fibrosis from local recurrence (LR). Materials and methodsSBRT treated non-small cell lung cancer (NSCLC) patients suspected of LR by conventional imaging underwent MRI: T2 weighted, diffusion weighted imaging, dynamic contrast enhancement (DCE) with a 5-minute delayed sequence. MRI was reported as high or low suspicion of LR. Follow-up imaging ≥12 months or biopsy defined LR status as proven LR, no-LR or not-verified. ResultsMRI was performed between 10/2017 and 12/2021, at a median interval of 22.5 (interquartile range 10.5–32.75) months after SBRT. Of the 20 lesions in 18 patients: 4 had proven LR, 10 did not have LR and 6 were not verified for LR due to subsequent additional local and/or systemic therapy. MRI correctly identified as high suspicion LR in all proven LR lesions and low suspicion LR in all confirmed no-LR lesions. All proven LR lesions (4/4) showed heterogeneous enhancement and heterogeneous T2 signal, as compared to the proven no-LR lesions in which 7/10 had homogeneous enhancement and homogeneous T2 signal. DCE kinetic curves could not predict LR status. Although lower apparent diffusion coefficient (ADC) values were seen in proven LR lesions, no absolute cut-off ADC value could determine LR status. ConclusionIn this pilot study of NSCLC patients after SBRT, multi-parametric chest MRI was able to correctly determine LR status, with no single parameter being diagnostic by itself. Further studies are warranted.

Needle tract seeding of a sclerosing epithelioid fibrosarcoma in a biopsy tract: a case report

BackgroundA sclerosing epithelioid fibrosarcoma (SEF) is an uncommon tumor of the deep soft tissue. An SEF has been described as a low-grade tumor with high local recurrence and metastatic rates. Generally, in bone and soft tissue tumors, a resection of the biopsy route is recommended; however, there is limited evidence with respect to the dissemination of the tumor tissue during a needle biopsy.Case presentationA mass in the right pelvic cavity, with no symptoms, was observed in a 45-year-old woman during a gynecological examination. Computed tomography (CT) revealed a multilocular mass with calcification in the pelvic cavity. The magnetic resonance imaging (MRI) showed an iso-signal intensity on T1 weighted images and hypo- and iso-signal intensity on T2 weighted images. The CT-guided core needle biopsy was performed using a dorsal approach, and the biopsy diagnosis was a low-grade spindle cell tumor. The tumor was excised using an anterior approach. The tumor tissue comprised spindle cells and epithelioid cells with irregular nuclei, and the immunohistological analysis was positive for vimentin and epithelial membrane antigen, which was consistent with a diagnosis of sclerosing epithelioid fibrosarcoma. Five years after the surgery, the MRI showed a tumor recurrence in the subcutaneous tissue of the right buttock, which was consistent with the needle biopsy tract. The patient underwent a tumor excision, and the resected tumor was similar to the primary tumor.ConclusionsThe recurrent tumor was excised with a surgical margin, and the tumor specimen had the histological features of a sclerosing epithelioid fibrosarcoma. It was difficult to investigate the association of the core needle biopsy with the tumor recurrence because the approach of the biopsy tract is usually same as that used in a tumor excision. However, the present case indicated the tumor may recur in the biopsy tract of a soft tissue sarcoma. Surgeons should be aware of the possibility of disseminating tumor tissues in a needle biopsy.

Programmed cell death ligand-1 (PD-L1) expression in desmoid tumors: a retrospective study.

Desmoid tumor is a rare benign but locally aggressive monoclonal and fibroblastic proliferation. It lacks metastatic potential but is associated with a high local recurrence after surgery. It is either characterized by the Beta-catenin gene (CTNNB1) or the adenomatous polyposis coli gene (APC) mutation. The most appropriate treatment approach is watchful waiting with periodic follow-ups for asymptomatic patients. However, symptomatic patients who are not good candidates for surgery due to high morbidity risk may benefit from medical therapy. The new drugs targeting programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) display promising results in many cancer types. This study assessed the PD-L1 status of desmoid tumors in 18 patients.Biopsy and resection materials of 18 patients diagnosed with desmoid tumors between April 2016 and April 2021 were retrieved and assessed for PD-L1 expression. The prepared slides were immunohistochemically stained with PD-L1 antibody using Leica Bond® automated immunohistochemistry stainer.No positive PD-L1 staining of the desmoid tumor cells was detected in any specimens. Intratumoral lymphocytes were present in all specimens. However, five of them were positively stained for PD-L1.Based on the results of our study, anti-PD-1/PD-L1 therapy may not be a valuable option in desmoid tumor treatment due to the lack of expression of PD-L1 by desmoid tumor cells. Nevertheless, the presence of positively stained intratumoral lymphocytes may warrant further studies.

Nodular type predominance of head and neck cutaneous malignant melanoma in Asian populations leads to poor outcome and low survival.

Cutaneous malignant melanomas of the head and neck (HNM) are proposed to have notable histological and clinical differences from those at other sites (other melanoma); however, HNMs among Asians have remained poorly understood. This study aimed to investigate the clinicopathological features and prognostic factors of HNM in Asians. Asian melanoma patients who underwent surgical treatment from January 2003 to December 2020 were retrospectively reviewed. The clinicopathological features and risk factors for local recurrence, lymph node metastasis, and distant metastasis were analyzed. Among 230 patients, 28 (12.2%) were diagnosed with HNM, and 202 (87.8%) with other melanoma. The histologic subtype significantly differed as the nodular type was predominant in HNM whereas the acral lentiginous type was predominant in other melanoma ( P < 0.001). HNM was significantly associated with higher local recurrence ( P = 0.045), lymph node metastasis ( P = 0.048), distant metastasis ( P = 0.023), and lower 5-year disease-free survival ( P = 0.022) than other melanoma. Ulceration was the risk factor for lymph node metastasis based on multivariable analysis ( P = 0.013). A high proportion of HNM present as the nodular subtype in Asians, leading to poor outcomes and low survival. Therefore, more cautious surveillance, evaluation, and aggressive treatment are required.

Abstract 2419: A multimodel preclinical platform to evaluate photodynamic therapy as a strategy to reduce local recurrence in myxofibrosarcoma and osteosarcoma

Abstract Sarcomas are heterogeneous and rare malignant tumors that develop from connective tissues. Myxofibrosarcoma (MFS) and Osteosarcoma (OS) are the main representative subtypes of Soft tissues and Bone sarcomas. Conventional treatment consists of surgical resection and neo/adjuvant chemotherapy. However, a challenging clinical feature is a high local recurrence rate, calling for the development of novel strategies to eradicate MFS and OS. Fluorescence-guided surgery (FGS), coupled with photodynamic therapy (PDT), enables to detect and eradicate malignant tissues using a light-sensitive photosensitizer (PS). These compounds could be retained by neoplastic cells to a greater extent than by healthy tissue. Thus, when photoactivated, they lead to cancer cell death, minimizing normal tissues toxicity. The project aims to provide a preclinical proof of concept of FGS and PDT for MFS and OS, allowing us to pave the way for a more effective treatment strategy. A multimodel preclinical platform of MFS and OS comprising 2D, 3D-collagen based scaffold was developed. A MFS stabilized cell line (IM-MFS-1) and four OS cell lines (Saos-2, U-2 OS, MG-63, 143B) were used. NIH-3T3 fibroblast cell line was used as healthy counterpart. We tested a panel of synthetic PSs: Toluidine Blue, 5-Aminolevulinic Acid hydrochloride (ALA), Methylene Blue, Chlorin e6 (Ce6), Pheophorbide a (Pba) and Al(III) Phthalocyanine Chloride Tetrasulfonic Acid (AlPcS4) that can be photoactivated with light in the 630-660 nm wavelengths’ range. The PSs were ranked on (a) selective uptake by tumor cells, respect to healthy cells and (b) the cytotoxic effect, after photoactivation. PSs cell uptake was evaluated by Countess II FL automated cell counter. Cytotoxicity was evaluated by WST-1 and Presto Blue assays. For each PS we determined the highest concentration, causing less than 50% dark toxicity in IM-MFS-1, OS cell lines and fibroblast NIH-3T3, seeded in 2D and 3D collagen-based models. Then, we evaluated the cell viability upon light irradiation (λ=630 or 660 nm; 10 mW/cm^2, 5 min). For all PSs, dark toxicity was very low. However, only Ce6 was effectively uptaken by tumor cells (% uptake &amp;gt; 60%) and not by NIH-3T3 cells (% uptake = 27%). Moreover, upon photoactivation, Ce6 induced significantly higher cell death in cancer cells as compared to NIH-3T3 cells, e.g. 1-3% cell viability in tumor cells and 76% cell viability in NIH-3T3. Results from our multimodel platform highlight PDT as a powerful strategy for the treatment of MFS and OS. Among the screened PSs, Ce6 is the most promising, showing a remarkable selectivity in tumor cells uptake and cytotoxicity. To increase the clinical significance of our approach, we will confirm its efficacy in patient-derived primary cultures; xenograft zebrafish in vivo embryos will be used to evaluate how PDT affects the disease aggressiveness and metastatic potential. Citation Format: Chiara Spadazzi, Micaela Pannella, Chiara Bellotti, Elisa Martella, Silvia Vanni, Alessandro De Vita, Chiara Liverani, Giacomo Miserocchi, Claudia Cocchi, Chiara Calabrese, Valentina Fausti, Roberto Casadei, Federica Pieri, Ania Naila Guerrieri, Giovanni Martinelli, Greta Varchi, Enrico Lucarelli, Laura Mercatali, Toni Ibrahim. A multimodel preclinical platform to evaluate photodynamic therapy as a strategy to reduce local recurrence in myxofibrosarcoma and osteosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2419.

PD07-10 OUTCOMES OF PARTIAL NEPHRECTOMY FOR NON-METASTATIC cT2 RENAL TUMORS: RESULTS FROM A CANADIAN MULTI-INSTITUTIONAL COLLABORATIVE

You have accessJournal of UrologyCME1 Apr 2023PD07-10 OUTCOMES OF PARTIAL NEPHRECTOMY FOR NON-METASTATIC cT2 RENAL TUMORS: RESULTS FROM A CANADIAN MULTI-INSTITUTIONAL COLLABORATIVE Rahul Bansal, Raees Cassim, Ryan Sun, Ranjeeta Mallick, Antonio Finelli, Simon Tanguay, Darrel Drachenberg, Frederic Pouliot, Luke Lavallee, Alan So, Ricardo Rendon, Lori Wood, Anil Kapoor, Aly-Khan Lalani, Naveen Basappa, Lucas Dean, Bimal Bhindi, Georg Bjarnason, and Rodney Breau Rahul BansalRahul Bansal More articles by this author , Raees CassimRaees Cassim More articles by this author , Ryan SunRyan Sun More articles by this author , Ranjeeta MallickRanjeeta Mallick More articles by this author , Antonio FinelliAntonio Finelli More articles by this author , Simon TanguaySimon Tanguay More articles by this author , Darrel DrachenbergDarrel Drachenberg More articles by this author , Frederic PouliotFrederic Pouliot More articles by this author , Luke LavalleeLuke Lavallee More articles by this author , Alan SoAlan So More articles by this author , Ricardo RendonRicardo Rendon More articles by this author , Lori WoodLori Wood More articles by this author , Anil KapoorAnil Kapoor More articles by this author , Aly-Khan LalaniAly-Khan Lalani More articles by this author , Naveen BasappaNaveen Basappa More articles by this author , Lucas DeanLucas Dean More articles by this author , Bimal BhindiBimal Bhindi More articles by this author , Georg BjarnasonGeorg Bjarnason More articles by this author , and Rodney BreauRodney Breau More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003231.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The role of partial nephrectomy (PN) is not well defined for cT2 renal cell carcinoma (RCC) as compared to radical nephrectomy (RN). The aim of this study was to examine oncological outcomes of PN as compared to RN for non-metastatic cT2 RCC. METHODS: The Canadian Kidney Cancer information system was used to define patients who underwent surgery for non-metastatic cT2 RCC from January 2011 to October 2022. Patients with clear-cell, papillary, and chromophobe RCC were included. Other histology, multiple tumours, and hereditary RCC syndrome patients were excluded. Each PN patient was individually matched to RN up to 1:4 depending on availability of patients based on tumor size (+/-1cm), histology, grade (clear cell and papillary), and necrosis (clear cell). Matched patients were analyzed as clusters. RESULTS: A total of 1523 patients were identified, and 50 PN patients met study criteria who were then matched to 185 RN patients. Both groups had similar age, gender, smoking status, BMI, Charlson comorbidity index score, symptoms at presentation, baseline eGFR, hemoglobin and pathological characteristics. PN patients had smaller tumors (7.6 cm [IQR 23] vs 8.4 [IQR 2.4], p=0.0479), had higher likelihood of undergoing open surgery (72.9% vs 31.8%, p<0.0001) and less likely received adrenalectomy (2% vs 24.3%, p=0.0004). Positive surgical margin rates were similar in both groups (8.2% in PN vs 3.4% in RN, p=0.2296). Median follow up was not significantly different in either group (3.6 yrs [IQR 4.7] in PN vs 3.3 [4.7] yrs in RN, p=0.975). During the follow up period, PN patients had higher risk of local recurrence (HR 3.0, 95%CI 1.08-8.37) and lower risk of metastasis (HR 0.36, 95%CI 0.15-0.88), overall survival (HR 0.36, 95%CI 0.18-1.78) as compared to RN. Cancer specific recurrence was similar between both groups (HR 0.56 ,95%CI 0.18,1.78). PN patients preserved more GFR than RN patients (-14.4 [SD 17.9] vs -23.7[SD 15], p=0.0006). Complications rates were similar between PN and RN (18% vs 8.65%, p=0.0571). CONCLUSIONS: In this multi-institutional Canadian cohort of patients with non-metastatic cT2 RCC undergoing surgery, PN compared to RN was associated with higher local recurrence, lower risk of distant metastasis, and death from any cause with similar complications and better preservation of renal function. Despite individual patient matching, there is likely unadjusted selection bias resulting in superior cancer survival associated with PN. Source of Funding: N/A © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e166 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Rahul Bansal More articles by this author Raees Cassim More articles by this author Ryan Sun More articles by this author Ranjeeta Mallick More articles by this author Antonio Finelli More articles by this author Simon Tanguay More articles by this author Darrel Drachenberg More articles by this author Frederic Pouliot More articles by this author Luke Lavallee More articles by this author Alan So More articles by this author Ricardo Rendon More articles by this author Lori Wood More articles by this author Anil Kapoor More articles by this author Aly-Khan Lalani More articles by this author Naveen Basappa More articles by this author Lucas Dean More articles by this author Bimal Bhindi More articles by this author Georg Bjarnason More articles by this author Rodney Breau More articles by this author Expand All Advertisement PDF downloadLoading ...

Crohn's Disease-Associated Anorectal Cancer Has a Poor Prognosis With High Local Recurrence: A Subanalysis of the Nationwide Japanese Study.

Colorectal cancer (CRC) is one of the major life-threatening complications in patients with Crohn's disease (CD). Previous studies of CD-associated CRC (CD-CRC) have involved only small numbers of patients, and no large series have been reported from Asia. The aim of this study was to clarify the prognosis and clinicopathological features of CD-CRC compared with sporadic CRC. A large nationwide database was used to identify patients with CD-CRC (n = 233) and sporadic CRC (n = 129,783) over a 40-year period, from 1980 to 2020. Five-year overall survival (OS), recurrence-free survival (RFS), and clinicopathological characteristics were investigated. The prognosis of CD-CRC was further evaluated in groups divided by colon cancer and anorectal cancer (RC). Multivariable Cox regression analysis was used to adjust for confounding by unbalanced covariables. Compared with sporadic cases, patients with CD-CRC were younger; more often had RC, multiple lesions, and mucinous adenocarcinoma; and had lower R0 resection rates. Five-year OS was worse for CD-CRC than for sporadic CRC (53.99% vs 71.17%, P < 0.001). Multivariable Cox regression analysis revealed that CD was associated with significantly poorer survival (hazard ratio 2.36, 95% confidence interval: 1.54-3.62, P < 0.0001). Evaluation by tumor location showed significantly worse 5-year OS and RFS of CD-RC compared with sporadic RC. Recurrence was identified in 39.57% of CD-RC cases and was mostly local. Poor prognosis of CD-CRC is attributable primarily to RC and high local recurrence. Local control is indispensable to improving prognosis.

Absorbable 3D-printed pancreaticojejunostomy device with a dual-layer drug coating for the prevention of postoperative local recurrence of pancreatic cancer

The high local recurrence rate of pancreatic cancer after surgery is one of the important risk factors affecting patient survival. The traditionally used silicone tube stent is not only complicated to operate but also lacks antitumor properties. The purpose of this study was to develop a dual-layer drug-coated pancreaticojejunostomy device. The coating consisted of two layers, an outer basic fibroblast growth factor (bFGF) coating layer and an inner nanoparticle albumin-bound paclitaxel (nab-PTX) coating layer with chitosan as the drug-carrying medium. Due to the diffusion barrier from the outer coating, the release of nab-PTX from the inner layer was delayed and slowed down. We studied the degradation rates, mechanical properties, surface morphologies, drug release kinetics, promoting the growth of fibroblasts and antitumor properties of the coated stents. It was found that 100 ng of bFGF and 50 µg of nab-PTX were suitable drug concentrations that can effectively promote the growth of fibroblasts and inhibit pancreatic cancer cells. The results also confirmed that the dual-layer drug-coated pancreaticojejunostomy device showed good antitumor activity both in vitro and in vivo without obvious systemic toxicity. In addition, the device has a suitable degradation rate. In conclusion, this biodegradable dual-layer drug-coated pancreaticojejunostomy device can potentially inhibit the local recurrence of pancreatic cancer after surgery and promote the healing of pancreaticointestinal anastomosis. This device has great potential to treat pancreatic cancer in the future.

Abstract P2-23-03: Genomic Evaluation of Malignant Phyllodes Tumors Reveals Multiple Targetable Opportunities

Abstract Background: Malignant phyllodes tumors (MPT) are rare fibroepithelial breast tumors that disproportionately affect young women. Despite high local and distant recurrence rates, treatment is almost exclusively surgical. With no known effective chemotherapy or targeted systemic therapy options, metastatic progression portends dismal prognosis. Current national guidelines do not recommend biomarker testing in the non-metastatic setting. Management of metastatic disease follows principles of soft tissue sarcoma recommending Next-Generation Sequencing on an individual basis for patients who may qualify for clinical trials or are refractory to standard therapies. In the largest genomic profiling effort of MPT to date, we sought to describe the genomic landscape of MPTs through comprehensive genomic profiling (CGP) and immunotherapeutic biomarker analysis. Methods: Cases of sequenced MPT were identified from a CLIA-certified, CAP-accredited laboratory database (Foundation Medicine, Cambridge, MA). Cases were categorized as localized/locally recurrent or metastatic. All cases underwent CGP by DNA extraction from FFPE samples using a hybrid capture, adaptor ligation-based next generation sequencing assay, and all classes of genomic alterations, microsatellite instability (MSI), and tumor mutational burden (TMB) were evaluated. PD-L1 expression by IHC was measured by the DAKO 22C3 assay (scored CPS) or the Ventana SP142 assay (scored as IC). Patient characteristics and results of CGP of MPT were summarized by either N (%) or median (range). Factors from MPT were compared to all cases of breast carcinoma in the lab database. Fisher’s Exact Tests were used to test for differences between groups and analysis of variance was used to test for differences for continuous variables. Results: Of 135 MPT cases identified; 94 (69.6%) were localized/locally recurrent (breast, chest wall, soft tissue, skin, or lymph node) and 41 (30.4%) were metastatic (73% lung, followed by bone, liver, other intraabdominal). All patients were female with a median age of 54 years (range 14-86). The median TMB across samples was 2.5 mut/Mb and only 3 were TMB-high tumors (&amp;gt;10mut/Mb). Over 1/3 (36.8%) of samples were PD-L1+ via Ventana SP142 assay (≥1) and 21.4% were PD-L1+ via Dako 22C3 assay (CPS ≥10). All evaluable cases (N=132) were microsatellite stable. The ten most commonly altered genes included TERT-promoter (69.7%), CDKN2A (45.9%), TP53 (37.8%), NF1 (35.6%), CDKN2B (33.3%), MED12 (28.9%), MTAP (27.7%), KMT2D (22.2%), PIK3CA (20.0%), PTEN (18.5%), and RB1 (18.5%); notably distinct in frequency from the breast carcinoma cohort (Table 1). Alterations in genes affecting cell cycle regulation (i.e. CDKN2A/B and TP53) were mutually exclusive from one another (p&amp;lt; 0.001). Several tumors harbored genomic alterations with FDA-approved indications in other tumor types were found including: NF1, PIK3CA, EGFR Exon 19/20 insertions, and BRAF V600E mutations. There were no statistically significant differences between alterations in localized/locally recurrent versus metastatic specimens. Conclusions: In the largest genomic evaluation of localized/locally recurrent or metastatic MPTs to date, multiple clinically actionable mutations for further exploration were found. TERT-promoter was altered in the majority of cases. PDL-1 was expressed in over 1/3 of cases suggesting that clinical investigation of immunotherapeutic strategies is warranted. Routine sequencing of metastatic MPT may provide additional information to guide treatment decisions and clinical trial enrollment. Table 1. Frequency of Genomic Alterations identified in 135 cases of Malignant Phyllodes Tumors. Citation Format: Laura H. Rosenberger, Richard F. Riedel, Natalie A. Danziger, Ethan Sokol, Jeffrey S. Ross, Sarah L. Sammons. Genomic Evaluation of Malignant Phyllodes Tumors Reveals Multiple Targetable Opportunities [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-23-03.

Regional recurrence of malignant peripheral nerve sheath tumor in upper extremity – a rare case report

Introduction: Malignant Peripheral Nerve Sheath Tumor (MPNST) are aggressive soft tissue sarcoma (STS), originally arising from neural cell components. MPNST had a relatively high local recurrence rate of 22% and a disease survival rate of 45 - 60%. In this study, we would like to report a rare case of recurrent MPNST affecting the upper arm region, with a history of previously resected MPNST at the patient's ipsilateral elbow. Case Presentation: A 38-years old male patient complained of an enlarging mass in his left anterior axilla Patient had a history of left elbow mass 2 years before and had resected twice. Eight months afterward, a new tumor grew from his left axilla. From the physical examination, the mass was fixated and firm with an oval shape, size 8 x 6 cm. From chest CT scan examination, it appeared a soft tissue mass surrounded with stranding fat had infiltrated his left teres major muscle. The mass was removed successfully and the pathology result revealed a grade 2 MPNST. Post-operative radiotherapy was then scheduled. Among many STS, MPNSTs are notorious for having a high recurrence rate. NF1 mutation, tumors deeper than fascia, large tumors, high-grade tumors, and tumors arising from the trunk, head, and neck are related to poor prognosis in MPNST. Surgeons' inadequate knowledge, unplanned resections, and their dependency on radiotherapy are other iatrogenic factors for recurrences. Conclusion: MPNST has high recurrent risk, especially in high-grade tumors, large or deep tumors, surgery with positive resection margins, and NF1 mutations. The primary option for treatment is surgery and radiation therapy.

Clinical analysis of 312 patients with stage IB1-IIA2 cervical squamous cell carcinoma and research on the influencing factors of postoperative recurrence

ObjectiveTo investigate the influencing factors of the recurrence of IB1-IIA2 cervical squamous cell carcinoma after surgical treatment, and to explore the relationship between high-risk human papillomavirus (HR-HPV) infection and postoperative cervical squamous cell carcinoma recurrence.MethodsPatients (n = 312) diagnosed with stage IB1-IIA2 cervical cancer and treated by radical hysterectomy and lymphadenectomy at this hospital were accrued between January 2014 and December 2016. The clinical data of these patients were analysed, and the association among clinicopathological factors, the association among clinicopathological factors, HPV infection and recurrences was investigated through Cox regression.ResultsThe median follow-up time was 59.2 months (with a range of 14–77.9 months). The pre-operative HPV infection rate was 85.3% (266/312), and 74 patients had a high level of HPV-DNA (> 5 × 106 copy number / 104 cells). Twenty-nine patients had a postoperative persistent high level of HPV-DNA (9.3%). On multivariate analysis, deep 1/3 stromal invasion (hazard ratio [HR] 114.79, 95% confidence interval [CI] 2.821–4670.111, p = 0.012*) and postoperative persistence of high HPV-DNA levels within 12 months (HR 269.044, 95% CI 14.437–5013.754, p < 0.001*) and 24 months (HR 31.299, 95% CI 1.191–822.215, p = 0.039*) were associated with a higher local recurrence rate.ConclusionContinuous high HPV-DNA levels within 24 months of an operation and deep 1/3 interstitial infiltration were independent risk factors for local recurrences of cervical cancer.

Cancer stem cell-derived extracellular vesicles preferentially target MHC-II-macrophages and PD1+ T cells in the tumor microenvironment.

Immunotherapy is an approved treatment option for head and neck squamous cell carcinoma (HNSCC). However, the response rate to immune checkpoint blockade is only 13% for recurrent HNSCC, highlighting the urgent need to better understand tumor-immune interplay, with the ultimate goal of improving patient outcomes. HNSCC present high local recurrence rates and therapy resistance that can be attributed to the presence of cancer stem cells (CSC) within tumors. CSC exhibit singular properties that enable them to avoid immune detection and eradication. How CSC communicate with immune cells and which immune cell types are preferentially found within the CSC niche are still open questions. Here, we used genetic approaches to specifically label CSC-derived extracellular vesicles (EVs) and to perform Sortase-mediated in vivo proximity labeling of CSC niche cells. We identified specific immune cell subsets that were selectively targeted by EVCSC and that were found in the CSC niche. Native EVCSC preferentially targeted MHC-II-macrophages and PD1+ T cells in the tumor microenvironment, which were the same immune cell subsets enriched within the CSC niche. These observations indicate that the use of genetic technologies able to track EVs without in vitro isolation are a valuable tool to unveil the biology of native EVCSC.

Therapie von Lebermetastasen

BackgroundThe liver is the main destination for distant metastases of gastrointestinal as well as other malignancies. Consequently, the therapy of liver metastases plays a key role in oncological treatment strategies.ObjectivesIn this review, the current treatment options and multimodal therapy strategies for liver metastases are presented.Materials and methodsCurrent literature and national/international consensus guidelines are reviewed and general treatment options for liver metastases are summarized and then presented for the respective malignancies.ResultsAccording to treatment strategy and prognosis, liver metastases are divided into three categories: colorectal liver metastases (CRLM), neuroendocrine liver metastases, and non-colorectal non-neuroendocrine liver metastases which include liver metastases of all other malignancies. Due to their highest incidence, CRLM are of major interest. The individual treatment is chosen according to patient’s oncological situation, liver function, and comorbidities.ConclusionsSurgery is the best curative treatment option. Thus, all patients should be evaluated for surgery in specialized oncological boards. Despite higher local recurrence, local ablation methods are good alternative options for small and limited metastases. Systemic treatments and radiation are implemented in palliative settings as well as multimodal treatment strategies with the goal of cure.

P463 Crohn’s disease–associated anorectal cancer has a poor prognosis with high local recurrence: a subanalysis of the Nationwide Japanese Study

Abstract Background Cancer is the worst prognostic factor for patients with Crohn’s disease (CD). Previous studies of CD-associated colorectal cancer (CRC) have involved only small numbers of patients, and no large series have been reported. The aims of this study are to clarify the prognosis and clinicopathological features of CD-CRC compared with sporadic CRC using a large nationwide database from the Japanese Society for Cancer of the Colon and Rectum. Methods A large nationwide database covering data from 1980 to 2020 was used to identify patients with CD-CRC (n=233) and sporadic CRC (n=129,783). The clinicopathological features, 5-year overall survival (OS), and 5-year recurrence free survival (RFS) for patients with CD-CRC were compared with these outcomes in sporadic CRC. The data were further analyzed based on tumor location in the colon (CC) or anus/rectum (RC). Propensity score (PS) matching was used to account for selection bias. A binomial logistic regression model was used to estimate the PS, using the nine effective covariates: age at cancer diagnosis, sex, CEA, surgical treatment, adjuvant chemotherapy, tumor depth, lymph node metastasis, distant metastasis, and residual tumor. Results Compared with sporadic cases, patients with CD-CRC were younger, more often had RC, multiple lesions, and mucinous adenocarcinoma. R0 resection was less common with CD-CRC (77.43%) vs sporadic CRC (90.99%; P&amp;lt;0.001). Five-year OS was worse with CD-CRC vs sporadic CRC (53.99% vs 71.17%, P&amp;lt;0.001). Evaluation by tumor location showed significantly worse 5-year OS and RFS with CD-RC compared with sporadic RC, whereas 5-year OS and RFS in CD-CC vs sporadic CC was comparable. A higher recurrence was found with CD-RC (39.57%) compared with sporadic RC (21.97%, P&amp;lt;0.001), but the recurrence rates did not differ between CD-CC and sporadic CC. The most frequent sites of recurrence in CD-RC were local. Following PS matching, 5-year RFS with CD-RC was significantly worse than with sporadic RC (52.41% vs 78.74%, P&amp;lt;0.001), but 5-year RFS did not differ between CD-CC and sporadic CC (81.07% vs 82.04%, P=0.900). Conclusion Poor prognosis with CD-CRC is attributable primarily to RC and high local recurrence. Local control is indispensable to improving prognosis.

Outcome After Surgical Treatment of Dermatofibrosarcoma Protuberans (DFSP): Does it Require Extensive Follow-up and What is an Adequate Resection Margin?

Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous tumour of indeterminate malignant potential. The mainstay treatment for DFSP is surgical resection. Given the reported high local recurrence rate, the ideal resection margin for DFSP is unclear. The purpose of this study was to ascertain the local recurrence and metastatic rate of DFSP and DFSP with fibrosarcomatous degeneration (FS-DFSP), with specific attention to margin status in an attempt to address the issue of margin adequacy. Patients treated for DFSP at a single sarcoma centre were identified from a prospective database. DFSP and FS-DFSP patients with and without prior surgery were included. Patients were followed after surgery to monitor complications, local recurrence and metastasis. The study included 200 patients: 166 patients with DFSP and 34 patients with FS-DFSP. In the DFSP group, nine patients (5.4%) had positive margins, one case (0.6%) developed local recurrence (LR) and no patients developed distant metastases. In the FS-DFSP group, seven patients (20.6%) had positive margins, six patients (17.6%) developed localrecurrence (LR) and eight patients (23.5%) developed distant metastases, of which three (37.5%) were in the lungs, one (12.5%) in bone and four (50%) in other soft tissue sites. Local recurrence and metastases are extremely rare in patients with DFSP. Achieving a negative as opposed to a wide surgical margin may be sufficient to avoid local recurrence of most DFSP. We suggest that no ongoing surveillance for local or systemic relapse is required for DFSP patients after negative margin resection. For FS-DFSP, we recommend the same surveillance schedule, based on tumour grade, as other soft tissue sarcoma.

Intraoperative Evaluation of Soft Tissue Sarcoma Surgical Margins with Indocyanine Green Fluorescence Imaging.

Soft tissue sarcomas (STS) are rare malignant tumors often associated with poor outcomes and high local recurrence rates. Current tools for intraoperative and definitive margin assessment include intraoperative frozen section and permanent pathology, respectively. Indocyanine green dye (ICG) is a historically safe fluorophore dye that has demonstrated efficacy for intraoperative margin assessment in the surgical management of both breast and gastrointestinal cancers. The utility of ICG in the surgical management of sarcoma surgery has primarily been studied in pre-clinical mouse models and warrants further investigation as a potential adjunct to achieving negative margins. This study is a prospective, non-randomized clinical study conducted on patients with confirmed or suspected STS. Patients younger than 18 years, with a prior adverse reaction to iodine or fluorescein, or with renal disease were excluded from the study. Intravenous ICG was infused approximately three hours prior to surgery at a dosage of 2.0-2.5 mg/kg, and following tumor resection, the excised tumor and tumor bed were imaged for fluorescence intensity. When scanning the tumor bed, a threshold of 77% calibrated to the region of maximum intensity in the resected tumor was defined as a positive ICG margin, according to published protocols from the breast cancer literature. ICG results were then compared with the surgeon's clinical impression of margin status and permanent pathology results. Out of 26 subjects recruited for the original study, 18 soft tissue sarcomas (STS) were included for analysis. Three subjects were excluded for having bone sarcomas, and five subjects were excluded due to final pathology, which was ultimately inconsistent with sarcoma. The average age of patients was 64.1 years old (range: 28-83), with an average ICG dose of 201.8 mg. In 56% (10/18) of patients, ICG margins were consistent with the permanent pathology margins, with 89% specificity. The use of ICG as an intraoperative adjunct to obtaining negative margins in soft tissue sarcoma surgery is promising. However, studies with larger sample sizes are warranted to further delineate the accuracy, optimal dosage, timing, and types of sarcoma in which this diagnostic tool may be most useful.

Long-Term Efficacy and Toxicity of Intensity-Modulated Radiotherapy in Bulky Cervical Cancer.

Treatment of bulky cervical cancer is associated with both high adverse effects and local recurrence rates with traditional box method radiotherapy. Intensity-modulated radiotherapy (IMRT) has been adopted for the treatment of cervical cancer in order to deliver more precise radiation doses to the target region. We retrospectively enrolled a total of 98 patients with cervical cancer ≥4 cm who completed IMRT and point A-based brachytherapy treatment. The median follow-up time of the cohort was 6.84 years, with the 5-year OS and DFS being 66.33% and 75.12%, respectively. In addition, 7.14% of patients experienced local recurrence, 12.24% had distant recurrence, 6.12% had both local and distant recurrence, and 3.06% had persistent disease. In the univariate analysis, lymph node metastasis, higher creatinine levels, higher initial CA-125 and receiving chemotherapy other than cisplatin were all associated with a worse PFS. A tumor size ≥6 cm was associated with an increased incidence of higher grade of acute diarrhea. Grade 3 late radiation proctitis and cystitis developed in 11.22% and 13.27% of patients, respectively. The local recurrence rates and overall efficiencies were not inferior to other studies involving traditional pelvic external beam radiation therapy with concurrent chemotherapy. The safety and efficacy of IMRT for bulky cervical cancer were acceptable.

Perineural Invasion Predicts Local Recurrence and Poor Survival in Laryngeal Cancer.

(1) Background: Perineural invasion (PNI) in head and neck cancer is associated with a poor prognosis; however, the effect of PNI on the prognosis of laryngeal cancer remains under debate. This retrospective study aimed to investigate the effect of PNI in fresh or salvaged larynges on survival in patients who had undergone laryngectomy for squamous cell carcinoma. (2) Methods: This study enrolled 240 patients diagnosed with laryngeal cancer who had undergone open surgery at Seoul St. Mary's Hospital, Korea. The effects of PNI, other histopathologic factors, and treatment history on survival and recurrence patterns were assessed. (3) Results: PNI was observed in 30 of 240 patients (12.5%). PNI (HR: 3.05; 95% CI: 1.90-4.88; p = 0.01) was a significant predictor of poor 5-year disease-free survival. In fresh cases, preepiglottic invasion (HR: 2.37; 95% CI: 1.45-3.88; p = 0.01) and PNI (HR: 2.96; 95% CI: 1.62-2.96; p = 0.01) were negative prognostic factors for 5-year disease-free survival. In the salvage group, however, only PNI (HR: 2.74; 95% CI: 1.26-5.92; p = 0.01) was a significant predictor of disease-free survival. Further, PNI significantly influenced high local recurrence (HR: 5.02, 95% CI: 1.28-9.66; p = 0.02). (4) Conclusions: Independent of treatment history, PNI is a prognostic factor for poor survival and local recurrence in laryngeal cancer.

Oncological and functional outcome in a rare case of clear cell chondrosarcoma of the proximal femur

Chondrosarcomas are the second most common bone sarcomas, accounting for less than 0.5% of all cancers. The treatment plan can be improved by analyzing clinical characteristics and treatment patterns. The rarity and slow-growing nature of this tumour often lead to prolonged symptoms and also initial misdiagnosis with avascular necrosis of the femur, benign bone lesions like chondroblastoma. The initial reports of this patient suggested avascular necrosis of the femur head. His pain became severe and further investigations were done, MRI confirmed the diagnosis of Chondrosarcoma. An image-guided core needle biopsy suggested Clear Cell Chondrosarcoma (CCC). Wide local resection with negative margins forms the mainstay of treatment since intralesional procedures predispose to a high local recurrence rate. A prolonged follow-up is required since late local recurrences of tumour and distant metastases are common.