Distant Lymph Node Involvement Research Articles

237. THE PROGNOSTIC VALUE OF NODAL SKIP METASTASIS IN PATIENTS WITH ESOPHAGEAL CANCER

Abstract Background Nodal skip metastasis (NSM), a common form of lymphatic spread in esophageal cancer (EC), refers to metastatic involvement of distant lymph nodes (LNs) without prior engagement of adjacent LNs. Previous studies examining the association between NSM and survival outcomes in EC patients have yielded inconsistent and even contradictory results. This systematic review and meta-analysis aim to assess the prognostic value of NSM and summarize NSM definitions used in prior studies. Methods Four databases were employed for this meta-analysis. The relationship between NSM and overall survival (OS) was assessed using pooled hazard ratios (HRs) and their 95% confidence intervals (CIs). Sensitivity analysis and funnel plots were utilized to evaluate publication bias. Results This meta-analysis incorporated nine studies, and the pooled results revealed no significant association between NSM and OS (HR = 0.99, 95% CI: 0.75–1.31; P = 0.951). Sub-group analyses based on histological features, method of lymphadenectomy, node staging system, and NSM definitions also failed to identify a significant association between NSM and OS. Conclusions Based on the available evidence, NSM cannot be considered a prognostic factor for EC patients. Future studies examining the prognostic value of NSM should focus on employing three-field lymphadenectomy with an adequate number of harvested LNs. NSM definitions based on lymph node station and anatomical compartment could both serve as feasible classifications for EC.

Heterogeneity of claudin 18.2 expression in metastatic gastric cancer

Claudin 18.2 has emerged as a viable therapeutic target in gastric cancer (GC), but little is known about the heterogeneity of its expression in GC. This study investigated the heterogeneity of claudin 18.2 expression in 166 patients with metastatic GC whose surgical or paired primary–metastatic specimens were available. The prevalence of claudin 18.2 positivity (moderate-to-strong expression in ≥ 75% by the 43-14A clone) was 47.0%. Claudin 18.2-positive tumors exhibited more frequent peritoneal metastasis and a lower incidence of hepatic and distant lymph node involvement. Survival outcomes were comparable between patients with claudin 18.2-positive and -negative tumors. Intratumoral heterogeneity was noted in 38.5% of surgical specimens. Paired primary-metastatic site analysis revealed that 25.2% of patients had discordant results for claudin 18.2 positivity. Across different metastatic organ categories, peritoneal lesions showed the highest positivity rate (44.3%) and positive concordance rate (31.4%), whereas liver lesions had the lowest positivity rate (17.9%) and concordance rate (12.8%). In conclusion, claudin 18.2 expression exhibits intratumoral and intrapatient spatial heterogeneity in metastatic GC. Claudin 18.2 positivity is associated with more frequent peritoneal metastasis, and peritoneal lesions are more likely to have positively concordant claudin 18.2 results with the primary site than other metastatic sites.

Prognostic value of tumour-related factors associated with canine retroperitoneal hemangiosarcoma in comparison with other anatomic presentations: A retrospective observational study.

Dogs with retroperitoneal hemangiosarcoma (HSA) exhibit variable postoperative median survival times (MST). To retrospectively evaluate the prognostic value of selected tumour-related factors, such as tumour size, rupture, invasion into adjacent tissue, involvement of lymph node and distant metastasis, they were analysed in dogs with retroperitoneal HSA. Ten dogs with retroperitoneal HSA managed solely with surgical excision were reviewed and compared with spleen (71) and liver (9) HSA. The Kaplan-Meier method and log-rank analysis were used compare MSTs between factors. Multivariable Cox proportional-hazard analysis was used to compare differences between arising sites. Retroperitoneal HSA showed comparatively longer postoperative MST compared with that of spleen and liver HSA and demonstrated significantly longer MST (p=0.003) for tumours ≥5cm (195 days) than <5cm (70 days). Spleen HSA revealed significantly shorter MSTs in involvement of distant lymph nodes (23 days) and distant metastasis (39 days) than those in negative (83 days, p=0.002 and 110 days, p<0.001, respectively). Liver HSA also revealed significantly shorter MST (16.5 days compared with 98 days, p=0.003) for distant metastasis. Additionally, hazard ratios (HRs) and their forest plot for overall HSA revealed as poor prognostic factors, arising sites (spleen; HR 2.78, p=0.016 and liver; HR 3.62, p=0.019), involvement of distant lymph nodes (HR 2.43, p=0.014), and distant metastasis (HR 2.86, p<0.001), and as better prognostic factor of tumour size ≥5cm (HR 0.53, p=0.037). In combination with overall HSA, retroperitoneal HSA shows comparatively longer postoperative MST compared to spleen and liver HSA, associated with tumour size ≥5cm suggesting better prognostic factor.

Survival outcome and optimal candidates of primary tumor resection for patients with metastatic medullary thyroid cancer.

Medullary thyroid cancer (MTC) often exhibits aggressive growth with distant organ metastasis, leading to poor survival. The question of whether primary tumor resection (PTR) is beneficial for patients with metastatic MTC remains a subject of debate. In this study, we evaluated the prognostic significance of organ-specific metastases and the number of metastatic organs in these patients, and we also conducted an analysis to determine the therapeutic value of PTR in managing this rare malignancy. Patients initially diagnosed with metastatic MTC were identified within the Surveillance, Epidemiology, and End Results (SEER) database. Univariable and multivariable Cox proportional hazards regression models were performed to identify survival predictors. Survival outcomes were calculated using the Kaplan-Meier method and compared using the log-rank tests. A total of 186 patients with metastatic MTC at initial diagnosis from 2010 to 2020 were included. Bone, lung and liver were the most common metastatic organs. Patients with brain metastasis had significantly worse overall survival (OS) (p = 0.007) and cancer-specific survival (CSS) (p = 0.0013). Among all patients, 105 (56.45%) underwent PTR, and this group showed reduced overall mortality (OM) and cancer-specific mortality (CSM) (all p < 0.05). When analyzing different metastatic patterns, PTR significantly lowered the risk of OM and CSM for patients with bone, lung, liver, or distant lymph node (DLN) involvement (all p < 0.05). Additionally, among patients with one or two metastases, those undergoing surgical resection were significantly associated with favorable OS (p = 0.008) and CSS (p = 0.0247). PTR may confer therapeutic benefits for carefully selected individuals with metastatic MTCs. To integrate these insights into clinical decision-making settings, it is imperative to undertake multicenter prospective studies in the future.

Camrelizumab plus apatinib and SOX as first-line treatment in patients with alpha-fetoprotein–producing gastric or gastroesophageal junction adenocarcinoma: A single-arm, multi-center, phase 2 trial.

351 Background: Patients (pts) with AFP-producing G/GEJ adenocarcinoma generally respond poorly to first-line standard chemotherapy. We aimed to assess the efficacy and safety of first-line camrelizumab plus apatinib given concurrently with chemotherapy, followed by camrelizumab plus apatinib in AFP-producing G/GEJ adenocarcinoma pts. Methods: In this open-label, single-arm, multi-center, phase 2 trial (NCT04609176), pts with aged ≥18 years, clinical stage III-IV, unresectable/recurrent or metastatic G/GEJ adenocarcinoma with no prior systemic therapy, serum AFP &gt; 2×ULN or AFP positive by the IHC staining method were enrolled. Pts received 4 cycles of standard S-1 plus oxaliplatin (SOX) and camrelizumab (200mg, iv, d1, q3w) plus apatinib (250mg, po, qd). Pts without disease progression then continued to receive camrelizumab plus apatinib for up to 24 months, or until progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per RECIST v1.1; secondary endpoints included the duration of response (DoR), disease control rate (DCR), progression free survival (PFS), overall survival (OS) and safety. Results: A total of 36 pts were enrolled and received treatment between Dec 4, 2020 and Aug 4, 2023. 35 pts were evaluable for tumor response. Median age was 63 years (range: 28, 78), with 30 pts (83.3%) were male. 13 pts (36.1%) presented with GEJ. 34 pts (94.5%) were diagnosed with stage IV. 20 pts (55.6%) had distant lymph node involvement, 18 (50.0%) had liver metastasis, 8 (22.2%) had peritoneal metastasis, and 2 (5.6%) had lung metastasis. Median serum AFP level was 739.8 ng/ml (range: 77.7, 321847.0). At data cut-off (Sep 1, 2023), the median follow-up duration was 6.4 months (range: 0.7, 27.0). Efficacy was assessed in the FAS population (n = 36). 2 pts showed complete response (CR, all confirmed), 22 had partial response (PR, 18 confirmed) and 7 had stable disease (SD). In consequent, the unconfirmed ORR was 66.7% (24/36) and DCR was 86.1% (31/36), with a confirmed ORR of 55.6% (20/36). The median PFS and OS were still immature. However, the estimated 12-month PFS rate was 42.1%. Any grade treatment-related adverse events (TRAEs) occurred in 33 pts (91.7%) and grade ≥ 3 in 13 (36.1%) pts. The most common grade ≥ 3 TRAEs were decreased neutrophil count (13.9%), hypertension (8.3%) and diarrhea (5.6%). 16 pts (44.4%) experienced immune-related adverse events (irAEs) of any grade. No new safety signals were reported. Conclusions: In AFP-producing G/GEJ adenocarcinoma pts who had not previously received systemic therapy, camrelizumab plus apatinib with SOX followed by camrelizumab plus apatinib showed promising antitumor activity and acceptable safety profile. Clinical trial information: NCT04609176 .

Linking EMT Status of Circulating Tumor Cells to Clinical Outcomes in Lung Cancer.

Lung cancer (LC) remains a leading cause of cancer-related mortality worldwide, with its prognosis influenced by complex biological factors. This study delves into the clinical relevance of circulating tumor cells (CTCs) and their Epithelial-Mesenchymal Transition (EMT) status in LC patients. We enrolled 30 newly diagnosed LC patients and utilized the CanPatrol technique for the separation and categorization of CTCs from peripheral blood samples. Immunofluorescent staining identified epithelial (CK8/18/19, EpCAM), mesenchymal (Vimentin, Twist), and leukocyte (CD45) markers in these cells. Fluorescence microscopy analyzed the slides, and RECIST 1.1 criteria assessed treatment response. Spearman's method was used to correlate CTCs' EMT states with their count and clinical characteristics. Our findings reveal three distinct CTC groups: epithelial (E-CTCs), hybrid epithelial/mesenchymal (E/M-CTCs), and mesenchymal (M-CTCs). Significant statistical differences were observed in stages III-IV vs I-II, tumor sizes T3-T4 vs T1-T2, and in the presence or absence of distant metastasis and lymph node involvement. Notably, the count of E/M-CTCs was positively correlated with TNM staging, tumor size, lymph node, and distant metastasis. Changes in M-CTC count pre- and post-treatment closely mirrored disease progression and control, showing considerable consistency with RECIST criteria. In conclusion, the EMT status of CTCs, especially E/M-CTCs, holds predictive value for LC staging, tumor size, and metastasis. Dynamic monitoring of M-CTCs can accurately reflect disease progression.

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: Outcomes for high-risk pediatric and adolescent and young adult (AYA) classic Hodgkin lymphoma (cHL) improved substantially with the addition of brentuximab vedotin (Bv) to AVEPC (adriamycin, vincristine, etoposide, prednisone, cyclophosphamide) chemotherapy. As patients with stage IV disease have poor outcomes, we evaluated the prognostic implications of sites contributing to stage IV disease. Methods: On AHOD1331 (NCT02166463), patients age 2–21 years with high-risk cHL (stage IIB with bulk, IIIB, IVA, and IVB) were randomized to 5 cycles of AB (bleomycin)VE-PC versus Bv-AVE-PC, and consolidative radiotherapy based on interim response and large mediastinal adenopathy at diagnosis. Patients with stage IV disease, as determined by protocol defined and centrally reviewed PET-CT, were identified. Stage IV was defined as disseminated involvement of ≥1 extralymphatic organ or tissues (with or without lymph node involvement) or isolated extralymphatic organ involvement with distant nodal involvement. E-lesions were distinguished from sites of stage IV involvement in the lung, but any liver and/or bone marrow involvement, regardless of contiguity, was considered stage IV. Central review was performed to confirm institutional classification of stage, upstaging 33 patients to stage IV and downstaging 17 among the 353 enrolled and stratified as Stage IV by the institution. Baseline characteristics and progression-free survival (PFS) were compared by pattern of metastatic involvement (lung only, bone only, bone marrow only, or multi-site, defined as >1 site of involvement). Results: 369 patients (median age 15 years, range 3–22) with stage IV disease treated on AHOD1331 were included, of which 183 (50%) were treated with ABVE-PC and 186 (50%) with Bv-AVE-PC. Patterns of disease included: isolated involvement of lung (185; 50%); bone marrow (5; 1%); or bone (8; 2%), and 171 (46%) had multi-site involvement. B symptoms were present in 80% and 88% with bone marrow or bone involvement respectively, 50% of those with lung, and 57% with multi-site disease. The 3 year-PFS (95% CI) by site of involvement was: 88.0% (82.3, 91.9) for lung, 100% for isolated bone marrow or bone, and 82.5% (75.8, 87.5) for multi-site (p = 0.21). Bv-AVE-PC significantly improved PFS among stage IV patients compared to ABVE-PC (3-year PFS 90.2% vs. 81.5%, p = 0.01). Among those with isolated lung involvement, there was a non-significant increased PFS with Bv (3-year PFS 91.2% vs. 84.7%, p = 0.16), while those with multi-site metastatic disease experienced significantly improved PFS with Bv (3 year-PFS 88.1% vs. 77.1%, p = 0.05). Conclusions: Among pediatric and AYA patients with stage IV cHL, PFS was notably improved with Bv among patients with multi-site metastatic involvement. These results will help guide future efforts to understand strategies to improve outcomes among children with stage IV disease. The research was funded by: Supported in part by grants from the National Institutes of Health (U10CA098543, U10CA180899, and U10CA180886; all to the Children’s Oncology Group), the Quality Assurance Review Center (U10CA29511), Imaging and Radiology Oncology Core Rhode Island (U24CA180803), and St. Baldrick’s Foundation (to the Children’s Oncology Group) Keywords: Hodgkin lymphoma, molecular targeted therapies, Lymphoid Cancers - Other No conflicts of interests pertinent to the abstract.

Primary Bone Lymphoma of the Knee: A Rare Entity

Introduction: The World Health Organization (WHO) defined primary bone lymphoma as a single bone lesion with or without regional lymph node involvement or multiple bone lesions without distant visceral or lymph node involvement. It is a rare entity; indeed, primary bone lymphomas represent 1-3% of non-Hodgkin's lymphomas, 5% of extra-nodal non-Hodgkin's lymphomas and 3% of primary bone tumors [2, 3]. Objective: The objective of our work is to clarify the imaging of a rare entity of primary bone lymphoma in a 6-year-old boy, who had been complaining for 1 month of pain in his right lower limb without functional impotence. Case Report: A 6 year old boy, who had been complaining for 1 month of pain in his right lower limb without functional impotence or other associated signs. The clinical examination revealed a child in good general condition, apyretic, with a limp when walking, limitation of all the articular amplitudes of the left he knee, a swelling of the homolateral thigh with discreet quadricipital amyotrophy. Examination of the lymph nodes did not identify any adenopathies. Standard radiographs of the left knee showed multiple lesions involving the lower extremities of the femur and the upper extremities of the tibia, with confluent intraspongiosa and areas of osteocondensation associated with localized cortical fracture without periosteal reaction. The biological workup revealed no abnormalities, including an LDH in the normal range. An MRI of the right thigh was requested for a better characterization of the lesion and to establish a locoregional extension assessment. It showed a large epiphyseal-metaphyseal lesion process of the lower end of the femur and epiphyseal-metaphyseal of the upper end of the left tibia in T1 hyposignal, locally infiltrating T2 heterogeneous hyper signal with vascular enclosure and popliteal ADPs. The CT scan was requested as part of the extension work-up and did not reveal any secondary lesion. The patient underwent a bone ........

Metastatic rhabdomyosarcoma with exclusive distant lymph node involvement: A European Pediatric Soft tissue sarcoma Study Group (EpSSG) report.

The prognosis of patients with metastatic rhabdomyosarcoma (RMS) is not uniformly poor. Tumors with nodal involvement beyond the first lymph node station are currently considered to have distant metastases. The aim of this study is to evaluate the characteristics and outcome of RMS patients with distal nodal involvement as the only site of metastasis. This study included all patients with a diagnosis of RMS and distant nodal involvement as the only metastatic site, enrolled in the European Pediatric Soft tissue sarcoma Study Group (EpSSG) protocols. Treatment comprised chemotherapy, surgery, and/or radiotherapy. The main outcome measures were event-free survival (EFS) and overall survival (OS). A total of 22 patients (median age 7.1years, range 1.4-16.7) fit the inclusion criteria. The extremities were the most common primary tumor site (59%). Twenty-one patients had regional and distant nodal involvement, 12 were PAX3/7-FOXO1 positive. Twenty patients had radiotherapy including 16 to the nodal metastatic area. After a median follow-up of 53.9months (range 22.8-110.5), 15 patients remain in complete remission, seven had progressive disease or relapse, and six of them died. The 3-year EFS and OS were 67.1% (95% confidence interval [CI]: 42.9-82.9) and 71.9% (95% CI: 47.7-86.3), respectively. Patients with fusion-negative tumors had better outcomes than those with fusion-positive tumors (3-year EFS 100% vs. 46.6%; p=.04). In our experience, patients with RMS and distant lymph node involvement as the only site of metastasis present an outcome superior than other metastatic patients and comparable to patients with locoregional nodal involvement. In particular, excellent outcomes were seen in the limited number of patients with fusion-negative tumors.

Interim PET-CT Scan to Improve Risk Modeling for Patients with Extranodal Natural Killer/T-Cell Lymphoma Treated with Non-Anthracycline Containing L-Asparaginase Based Regimen

Background Extranodal natural killer/T-cell lymphoma (ENKTL) is a rare and distinct subtype of non-Hodgkin lymphoma characterized by predominant involvement of the nasal cavity and nasopharynx and the application of L-asparaginase (L-asp) based non-anthracycline containing induction therapy has improved clinical outcomes of the patients. Currently, prognostic index of natural killer lymphoma plus Epstein-Barr virus is widely used to evaluate prognosis of patients with ENKTL. In this study, we evaluated the value of interim fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) for the better prognostication of ENKTL patients. Methods Patients with histologic diagnosis of ENKTL from May 2009 to May 2020 treated with L-asp based non-anthracycline containing induction regimen and who had interim PET-CT analysis at Asan Medical Center, Seoul, Korea were included. Response was assessed using the Deauville 5-point scales (DS). Progression-free survival (PFS) was defined as time from the induction therapy to disease progression or any cause of death, and overall survival (OS) was defined as time from the induction therapy to any cause of death. Survival curves were estimated by Kaplan-Meier method and compared using log-rank test. Key baseline characteristics and candidate prognostic factors including age, Eastern Cooperative Oncology Group performance status, Epstein-Barr virus (EBV) detection from blood at baseline, distant lymph node (LN) involvement, initial stage, location of disease (nasal vs. non-nasal), and serum lactate dehydrogenase level were included in the univariate analysis. In the multivariate analysis, variables exhibiting a potential association with survival (p < 0.05) in the univariate analysis were included. Results A total of 58 patients were included in the analysis. Median age was 55 years (range, 19-80), 34 patients (58.6%) were male, 19 patients (32.8%) had non-nasal disease and 43 patients (74.1%) had stage 4 disease at diagnosis. Among 43 patients with stage 4 disease, 19 patients (44.2%) received VIDL regimen consisting of etoposide, ifosfamide, dexamethasone and L-asp while 23 patients (55.8%) received SMILE regimen consisting of ifosfamide, etoposide, methotrexate, dexamethasone and L-asp as induction treatment. All 15 patients with stage 1 or 2 disease received combined modality treatment with cisplatin-based concurrent chemoradiation and L-asp containing chemotherapy. With median follow-up duration of 52.7 months (95% confidence interval [CI] 37.7-81.3), median PFS and OS were 9.9 months (95% CI 4.8-28.6) and 25.6 months (95% CI 13.3-not applicable), respectively. Thirty-two patients (55.2%) had interim PET-CT DS (iDS) of 4-5. Patients with iDS 4-5 showed significantly worse outcomes in terms of both PFS and OS compared to patients with iDS 1-3 with hazards ratio (HR) of 2.13 (95% CI 1.11-4.06, p = 0.019) and 2.51 (95% CI 1.19-5.33, p = 0.013), respectively. The 2-years PFS rates for patients with iDS 4-5 and iDS 1-3 were 27.3% (95% CI 15.3-44.8) and 49.0% (95% CI 32.9-69.3), respectively. The 2-years OS rates were 35.6% (95% CI 22.1-54.0) and 64.3% (95% CI 48.0-86.2), respectively. In the univariate analysis, age, EBV detection from blood at baseline, initial stage, location of disease (nasal vs. non-nasal), distant LN involvement and iDS showed potential association (p < 0.05) with OS. In multivariate analysis, iDS were independently associated with OS with HR of 3.96 (iDS 4-5 vs. 1-3, 95% CI 1.76-8.94, p < 0.001), along with location of disease with HR of 4.03 (non-nasal vs. nasal, 95% CI 1.83-8.91, p < 0.001). Conclusion The interim PET-CT response based on the DS is useful for predicting OS of patients with ENKTL in the era of non-anthracycline-based L-asp containing induction therapy.

The Prognostic Value of Nodal Skip Metastasis in Patients with Esophageal Cancer: A Systematic Review and Meta-Analysis.

Esophageal cancer (EC) is the sixth leading cause of cancer deaths worldwide. Nodal skip metastasis (NSM), a common form of lymphatic spread in EC, can be defined as the metastatic involvement of distant lymph nodes (LNs) without prior involvement of adjacent LNs. The results of the previous studies investigating the association between NSM and survival outcomes in patients with EC were inconsistent and even contradictory. The aim of this systematic review and meta-analysis is to investigate the prognostic value of NSM and to summarize the NSM definitions of EC in previous studies. Four databases were used in this meta-analysis. The association between NSM and overall survival (OS) was evaluated by using pooled HRs and their 95% confidence interval (CI). The sensitivity analysis and funnel plot were used to assess the publication bias. Nine studies were included in this meta-analysis. The pooled results of meta-analysis indicated that there was no significant association between NSM and OS (HR = 0.99, 95% CI: 0.75-1.31; P = 0.951). Meanwhile, according to the results of sub-group analysis on the basis of histological feature, method of lymphadenectomy, node staging system, and NSM definitions, no significant association was found between NSM and OS. On the basis of available evidences, NSM could not be used as a prognostic factor for patients with EC. For future studies investigating the prognostic value of NSM, only three-field lymphadenectomy with adequate harvested LNs can be performed. NSM definitions based on lymph node station and anatomical compartment could both be feasible classification for EC.

S1879 A Diagnostically Challenging Case of Primary Pancreatic Lymphoma

Introduction: Primary Pancreatic Lymphoma (PPL) is the exceedingly rare instance of extranodal Non-Hodgkin's Lymphoma developing mainly in the pancreas. We report a diagnostically challenging case of a patient presenting with a rapidly growing pancreatic mass, found to have PPL. Case Description/Methods: A 48-year-old female with past history of tobacco use presented with several months of cramping abdominal pain following COVID-19 infection. She denied weight loss, fevers, or night sweats. Her physical exam, CBC, CMP, lipase, LDH, and CA 19-9 were unremarkable. An abdominal ultrasound revealed a 2.8 x 1.9 x 3 cm cystic mass of the pancreatic head, most congruent with a pseudocyst. Worsening abdominal pain prompted repeat ultrasound one month later, which showed a doubling in size. Endoscopic ultrasound (EUS) with fine needle aspiration of the cystic mass and surrounding lymph nodes yielded cystic contents and reactive lymphadenopathy. Two months later, her abdominal pain worsened and repeat imaging showed further doubling in size with encasement of the celiac plexus. A second FNA performed via EUS redemonstrated cystic contents. An ultrasound-guided core needle biopsy of the mass revealed necrotic CD30+ diffuse large B cell lymphoma (DLBCL). PET scan was suggestive of stage IV PPL (Figure). Imaging also identified an inguinal lymph node that returned as CD10+ BCL6+ high grade follicular lymphoma, which was thought to be a distinct lesion. She was started on R-CHOP. Her clinical course was complicated by the formation and subsequent rupture of a splenic artery pseudoaneurysm, gastrointestinal bleeding, anuric kidney injury, and intestinal ischemia. She ultimately transitioned to comfort care. Discussion: Primary pancreatic lymphoma comprises 0.6% of extranodal lymphomas and 0.2% of primary pancreatic tumors. The clinical presentation is often vague and includes abdominal pain, B symptoms, jaundice, or bowel obstruction. The diagnostic criteria according to the WHO requires that the (1) majority of tumor burden be localized to the pancreas and (2) existing nearby and distant lymph node involvement should be secondary to pancreatic presentation. A biopsy is required to diagnose PPL, which is histologically most often DLBCL. Our case highlights the challenges associated with diagnosing PPL despite two EUS with FNA. Although rare, one should proceed with a high index of suspicion for PPL in any patient presenting with a rapidly enlarging pancreatic mass.Figure 1.: CT image of necrotic pancreatic mass.

Capecitabine in pretreated metastatic pulmonary lymphoepithelioma-like carcinoma: A retrospective study.

9093 Background: Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare disease, sharing common histological features with the undifferentiated subtype of nasopharyngeal carcinoma (NPC), and being under-represented in non-small cell lung cancer trials and clinical guidelines. While gemcitabine-based platinum doublet chemotherapy is more established in 1st line treatment of stage IV disease, there is limited evidence for subsequent treatment strategy. Oral capecitabine is one of the active agents in metastatic NPC, and was observed to have encouraging outcomes in pulmonary LELC. Methods: All consecutive patients with pulmonary LELC in 2010 – 2019 treated in a tertiary institution were reviewed. Patients with metastatic disease who progressed after gemcitabine-based platinum doublets and treated with capecitabine were included. Capecitabine was given at 1250 mg/m2 twice daily for 14 days followed by 7 days of rest in each cycle. Treatment response was monitored by clinical history, physical examination and imaging. Treatment was continued till drug holiday, intolerance or disease progression. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Clinical predictors for PFS and OS were analyzed using log-rank test and the Cox proportional hazard model. Results: Of the 140 LELC patients identified, 36 patients satisfied the above inclusion criteria (14 male, 22 female). Median age was 58.6 years old (range 41.5 – 75.6). All patients had an ECOG performance score of 0 or 1. 16 patients (44.4%) received 2 or more lines of prior systemic treatment. Median capecitabine cycles received was 5 (range 2 – 68). Objective response rate was 27.8% (complete response: 5.6%; partial response: 22.2%), disease control rate was 75.0%. With a median follow-up of 15.3 months (range 1.8 – 82.6), the median PFS and OS were 5.4 months (95% CI, 2.1 – 8.8) and 15.4 months (95% CI, 10.0 – 20.7) respectively. Capecitabine was generally well tolerated, with 22.2% grade 3 or above side effects, and 5.6% treatment termination due to intolerance. Bone and distant lymph node (LN) involvement were significant predictors of poorer PFS on multivariate analyses (bone: HR 3.24, 95% CI 1.44 – 7.29, p=0.004; distant LN: HR: 2.62, 95% CI 1.14 – 6.02, p=0.024). Age, sex, smoking history, number of treatment lines, and other sites of disease involvement were not significant predictors. Conclusions: This is to date the largest reported cohort of capecitabine in pre-treated metastatic pulmonary LELC. Capecitabine is effective and well tolerated, and should be considered as a treatment option after 1st line platinum-based chemotherapy. Future studies are warranted to delineate the optimal treatment pathway of this rare disease entity.

Myriad Manifestations of Gallbladder Carcinoma on Multidetector Computed Tomography: Retrospective Study of 230 Patients from Tertiary Care Centre of North India

Background: Gallbladder carcinoma is endemic in India. Though imaging findings of gallbladder carcinoma are very well-described in the literature, the research question that guided this study was to evaluate various imaging manifestations of the disease in this particular geographic region of North India which is a highly endemic region for gallbladder cancer and compare with studies from other parts of the world. Aims and Objective: The purpose of the study was to retrospectively analyse spectrum of findings on Multidetector Computed Tomography (MDCT) in histologically proven gallbladder carcinoma detected at a tertiary care centre from the NorthIndia. The primary objective was to define the various patterns of growth while the secondary objective was to analyse the specific prevalence and patterns of spread of the disease. Materials and Methods: We retrospectively studied contrast enhanced Computed Tomography (CECT) findings in 230 patients of histologically proven gallbladder carcinoma. Patients with previous cholecystectomy or biliary intervention were excluded. Results: In our study, focal or asymmetrical wall thickening of the gallbladder was the most common growth pattern seen in 140(61%) patients. Contiguous infiltration of liver was seen in 190 (83%) cases. Regional nodal involvement was observed in 90 (39%) patients, while 100 (43%) patients had both regional &amp; distant nodal involvement. Liver and peritoneal metastases were noted in 71 (31%) patients and 96 (42%) patients respectively. Majority (81%) of patients had stage IV disease. Conclusion: MDCT provides comprehensive information regarding the local extent as well as distant spread of gallbladder carcinoma. Asymmetric gall bladder wall thickening in this geographical region must be considered suspicious and should evoke histopathological analysis to exclude malignancy.

A real-world, population-based study for the outcomes of patients with metastatic colorectal cancer to the liver with distant lymph node metastases treated with metastasectomy.

Aim: To assess the impact of metastasectomy on survival outcomes of patients with concurrent liver and distant nodal metastases. Materials & methods: Surveillance, Epidemiology, and End Results (SEER) database was accessed and patients with colorectal liver metastases (with or without distant lymph node involvement) were reviewed. Kaplan-Meier survival estimates were then used to assess the impact of the presence of distant lymph node metastases as well as the impact of metastasectomy on overall and cancer-specific survival. A propensity score matching was then conducted between patients with distant lymph node metastases who had surgery versus those who did not have surgery. Results: A total of 15,325 patients were included in the current analysis including 1603 patients who have liver and distant nodal metastases (10.5%) and 13,722 patients who have liver metastases only (89.5%). The following factors were associated with better overall survival (OS): younger age (hazard ratio [HR] with increasing age: 1.024; 95% CI: 1.022-1.025), white race (HR for African-American race vs white race: 1.233; 95% CI: 1.175-1.295), distal site of the primary (HR: 0.808; 95% CI: 0.778-0.840), absence of distant lymph nodes (HR: 0.697; 95% CI: 0.659-0.737), metastasectomy (HR for no metastasectomy vs metastasectomy: 1.954; 95% CI: 1.858-2.056). Within the postpropensity cohort, metastasectomy was associated with improved OS among patients with concurrent distant lymph node and liver metastases (median OS of 20 vs 11 months; p < 0.001). Conclusion: Metastasectomy seems to be associated with improved survival among patients with concurrent lymph node and liver metastases. It is unclear if improved survival is related to the surgical intervention or to the fact that surgically treated patients have a better baseline general condition and hence improved outcomes.

Clinicopathological Profile of Thyroid Carcinoma in Young Patients: An Indonesian Single-Center Study.

Introduction Thyroid cancer is the third most common cancer that occurs in children and adolescents. Papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy. Although the mortality rate of thyroid malignancy in children is usually low, the disease recurrence is higher in children with more severe clinical presentation than in adults. This study aimed to determine the demographic and clinicopathological characteristics and outcome of pediatric and adolescent patients with thyroid malignancy in Indonesia. Methods The retrospective study included all patients diagnosed with thyroid carcinoma aged <20 years, from January 1, 2015, to December 31, 2019. Twenty-nine subjects fulfilled the inclusion and exclusion criteria. We retrieved baseline characteristics, pathology features, TSH and fT4 status, radioactive iodine therapy data, and patients' outcomes. Then, data were analyzed using the chi-square or Fisher's exact method. Results We identified 29 eligible subjects, including 3 boys and 26 girls. The most common type of thyroid carcinoma was PTC (96.5%), and follicular type (31%) was the predominant variant of PTC. Lymph node involvement occurred in 24% of patients, while distant metastasis occurred in 17.2% of patients with PTC. Twenty-four (82.7%) patients had stage 1 disease. Disease recurrence was recorded in 31% of patients during the study period with a median follow-up time of 24 months. Conclusion PTC is the most frequent type of thyroid carcinoma among children and adolescents. This malignancy has a low mortality rate, but the recurrence rate remains high among younger patients than adults even during a short-term follow-up analysis. Distant metastasis and lymph node involvement are commonly found in this age group.

Nutrition-Incorporated Pink-E Predicts Survival of Extranodal NK/T-Cell Lymphoma

▪Introduction: Patients with aggressive lymphomas are at high risk of losing body resources, resulting in malnutrition, immunodeficiency, impaired life quality and inferior outcomes. Nutritional status is closely associated with the development and treatment arrangements of malignancies, but often neglected in the prognostic assessment. Thus, this study aimed to explore the prognostic significance of nutrition-related parameters in extranodal NK/T-cell lymphoma (ENKTL), an aggressive lymphoma with dismal outcomes.Methods: We retrospectively analyzed patients diagnosed with ENKTL between 2011 and 2020 from Shandong Provincial Hospital and Affiliated Hospital of Qingdao University. The observation endpoints were overall survival (OS) and progression-free survival (PFS). Univariate (UVA) and multivariate (MVA) Cox regression analyses were conducted to examine the significance of variables at diagnosis on OS and PFS. A reformative nutrition assessment-incorporated score system was constructed based on the MVA results. Its performance was tested in the training and validation cohort from multiple aspects, including calibration, discrimination and clinical utility.Results: A total of 160 patients with a median age of 50 (39, 58.75) years and male predominance (67.5%) were included. The prognostic significance of two emerging nutritional indexes, prognostic nutritional index (PNI) and controlling nutritional status (CONUT) score, was assessed. UVA analysis showed PNI was a meaningful marker to OS (HR 2.275, P=0.014) but not to PFS (HR 1.653, P=0.089) while CONUT score was a significant predictor not only to OS (HR 29.385, P＜0.001) but to PFS (HR 12.516, P＜0.001). MVA analysis further verified that CONUT score could independently predict OS (HR 10.247, P=0.001) and PFS (HR 5.587, P=0.001) in addition to prognostic index of natural killer lymphoma plus EBV (PINK-E), another independent marker (PINK-E=2, HR 3.842, P=0.034, PINK-E=3/4/5, HR 9.185, P=0.006 for OS; PINK-E=2, HR 2.308, P=0.06, PINK-E=3/4/5, HR 4.535, P=0.004 for PFS) (Figure 1).Based on this finding, a modified prognosis scoring tool, CONUT-PINK-E, was developed from the training cohort (TC) and tested in the independent external validation cohort (VC). The novel model contains six factors, age≥60 years old, Ann Arbor III/IV stage, distant lymph node involvement, non-nasal type, detectable EBV-DNA in blood and CONUT score≥5 (moderate and severe malnutrition). CONUT-PINK-E differentiated patients into low-, intermediate- and high-risk grades according to the imparities of survival probability revealed by Kaplan-Meier curves. Significant survival differences existed among three risk grades that the median OS was 74, 36, 5 months and median PFS was 31, 14, 4 months, respectively, for the low-, intermediate-, high-risk group (P＜0.001) in TC and the corresponding data were 72, 26, 7 months and 35, 14, 4 months in VC (P＜0.001, Figure 2).Subsequently, the superiority of CONUT-PINK-E was examined by comparison with international prognostic index (IPI), Korean Prognostic Index (KPI), Prognostic index of natural killer lymphoma (PINK) and PINK-E. The 1- to 5-year time-dependent areas under receiver operating characteristic curve (AUCs) hinted that CONUT-PINK-E (TC: 0.832-0.961, VC: 0.773-0.937) possessed higher discrimination than IPI (TC: 0.710-0.785, P<0.001; VC: 0.646-0.840, P<0.001), KPI (TC: 0.659-0.826, P<0.001; VC: 0.623-0.691, P<0.001), PINK (TC: 0.802-0.865, P<0.001; VC: 0.663-0.842, P<0.001) and PINK-E(TC: 0.815-0.902, P<0.001; VC: 0.741-0.894, P<0.001) (Figure 3A, 3B). Decision curve analysis plainly showed CONUT-PINK-E brought higher clinical net benefits than IPI, KPI, PINK and PINK-E in forecasting OS and PFS of ENKTL (Figure 3C, 3D). In addition, net reclassification index (NRI) and integrated discrimination improvement (IDI) conformably demonstrated that CONUT-PINK-E achieved significant improvements than the prior stratification tools.Conclusion: This is the first time that CONUT score was recognized capable of acting as an independent prognostic marker in newly-diagnosed ENKTL patients. More importantly, the first risk score covering nutritional status assessment for ENKTL, CONUT-PINK-E, was proposed and presented striking performance. The newly-built model could deliver vital reference to the risk stratification and comprehensive managements of ENKTL patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Role of 18F-FDG-PET/CT in the staging of metastatic rhabdomyosarcoma: a report from the European paediatric Soft tissue sarcoma Study Group

BackgroundInitial staging of rhabdomyosarcoma is crucial for prognosis and to tailor the treatment. The standard radiology workup (SRW) includes magnetic resonance imaging, chest computed tomography (CT) and bone scintigraphy, but 18 Fluorine-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) (18F-FDG-PET/CT (PET-CT)) use is increasing. The aim of this study was to evaluate the impact of PET-CT in the initial staging of patients with metastatic rhabdomyosarcoma enrolled in the European protocol MTS2008. MethodsTwo authors retrospectively reviewed the SRW and PET-CT reports comparing the number and sites of metastases detected. For bone marrow involvement, PET-CT and bone marrow aspirates/biopsies were compared. ResultsAmong 263 metastatic patients enrolled from October 2008 to December 2016, 121 had PET-CT performed at diagnosis, and for 118 of 121 patients, both PET-CT and radiological reports were available for review. PET-CT showed higher sensitivity than SRW in the ability to detect locoregional (96.2% versus 78.5%, P value = 0.0013) and distant lymph node involvement (94.8% versus 79.3%, P value = 0.0242), but sensitivity was lower for intrathoracic sites (lung 79.6% versus 100%, P value = 0.0025). For bone metastasis, PET-CT was more sensitive than bone scintigraphy (96.4% versus 67.9%, P value = 0.0116). The PET-CT sensitivity and specificity to detect marrow involvement were 91.8% and 93.8%, respectively. The mean number of metastatic sites was 1.94 (range 0–5) with PET-CT and 1.72 (range 0–5) with SRW. In four patients (3.4%), PET-CT changed the staging from localised to metastatic disease. ConclusionPET can identify metastatic disease not evident on SRW in a small number of patients. This is because of its higher ability to recognise lymph node and bone involvement. Chest CT remains essential to detect lesions in intrathoracic sites, which can be performed in a one stop-shot routine examination or on a dedicated chest CT scan. PET-CT could replace bone scintigraphy to study bone involvement.

Site-specific metastases of gallbladder adenocarcinoma and their prognostic value for survival: a SEER-based study

BackgroundGallbladder cancer is a rare but highly malignant cancer, which often progresses to a metastatic stage when diagnosed because of its asymptomatic manifestation. In this study, we intended to analyze the prognostic value of metastatic gallbladder adenocarcinoma (GBA) with site-specific metastases.MethodsUsing the Surveillance, Epidemiology, and End Results (SEER) database, GBA patients diagnosed with metastases between 2010 and 2016 were selected to identify the prognosis according to the isolated metastatic sites, including liver, lung, bone, brain and distant lymph nodes (DL). Kaplan–Meier methods were used for survival comparisons and multivariable Cox regression models were constructed to find out independent factors that associated with survival.ResultsData from 1526 eligible patients were extracted from the SEER database. Among the patients, 788 (51.6%) had isolated liver metastases, 80 (5.2%) had isolated distant nodal involvement, 45 (2.9%) had isolated lung metastases, 21 (1.4%) had isolated bone metastases, 2 (0.1%) had isolated brain metastases and 590 (38.7%) had multiple metastases. No significant survival difference was shown between patients with single or multisite metastases (P > 0.05). Patients with isolated lung or DL metastases had significant better survival outcomes than those with isolated bone metastases (P < 0.05). Multivariate analysis showed that performing surgery at primary site, receiving chemotherapy were associated with better OS and CSS for patients with isolated liver or DL metastases.ConclusionsThe study showed that different metastatic sites affect survival outcomes in metastatic GBA patients. Highly selected subset of patients with liver or DL metastases might benefit from surgery at primary site.

Primary Mediastinal (Thymic) Large B-Cell Lymphoma: Fidelity of Diagnosis Using WHO Criteria

PurposeDiagnosing primary mediastinal (thymic) large B-cell lymphoma (PMBCL) is challenging because it is a clinicopathologic entity that shares characteristics with other lymphomas and lacks pathognomonic features. We sought to investigate the fidelity between a working diagnosis of PMBCL at our institution and the clinicopathologic criteria established within the 2017 World Health Organization (WHO) classification. Patients and MethodsMedical records and archived tissue of patients treated for stage I-II PMBCL from 1998 to 2018 were retrospectively reviewed for clinical and pathologic conformity with current WHO criteria. Disease was characterized as definitely PMBCL if all of the following were present: anterior mediastinal mass with or without lymph node involvement, no extranodal disease, B-cell antigen expression, Epstein-Barr virus negativity, and at least one supportive feature: female gender under age 40, bulky primary tumor, CD30 weakly positive, compartmentalizing alveolar fibrosis, lack of surface immunoglobulin expression, and MUM1 or CD23 positivity. Disease without supportive features or other pathologic findings more suggestive of other entities was characterized as equivocal for PMBCL. Lack of an anterior mediastinal mass, presence of distant lymph node involvement or extranodal disease, lack of B-cell antigen expression, or Epstein-Barr virus positivity were characterized as definitely not PMBCL. Clinical management and outcomes were also assessed. ResultsOf 63 patients treated for presumed stage I-II PMBCL, 58 (92%) met the criteria for PMBCL. The most common reason for a discordant diagnosis was lack of an anterior mediastinal mass (n = 3). Two additional patients were characterized as having disease equivocal for PMBCL. In retrospect, one patient most likely had a mediastinal gray zone lymphoma due to CD15 positivity and another diffuse large B cell, not otherwise specified, at pathologic review. Five-year progression-free and overall survival were 67% (95% confidence interval, 54-77) and 81% (95% confidence interval, 68-89), respectively, for all patients. ConclusionDespite the complexity of the clinicopathologic criteria of PMBCL, most patients (92%) who were treated for stage I-II PMBCL at our institution appear to have been accurately diagnosed.