Locoregional Node Involvement Research Articles

Current Preoperative Management of Vulvar Squamous Cell Carcinoma: An Overview.

Vulvar carcinoma is a rare cancer affecting the genital tract, constituting 4% of gynecological tumors. Vulvar squamous cell carcinoma (VSCC) is the most common type. Diagnosis relies on biopsy during vulvoscopy, plus imaging such as ultrasonography (USG), magnetic resonance imaging (MRI) and positron emission tomography (PET). This review aims to lay out a thorough overview as to the current preoperative management of VSCC, both in case of vulvar and lymph node involvement. The data research was conducted using the following databases: MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID and Cochrane Library from 2010 to 2024. The selection criteria included only original articles. Seventeen studies were assessed for eligibility. A concordance rate of 62.3% for vHSIL and 65.2% for carcinoma at vulvoscopy, with a sensitivity of 98%, specificity of 40%, PPV (Positive Predictive Value) of 37% and NPV (Negative Predictive Value) of 98% in identifying malignant lesions was found. Regarding the reliability of PET for staging and assessing lymph node involvement, a mean SUV (Standardized Uptake Value) for malignant vulvar lesions of 8.4 (range 2.5-14.7) was reported. In the case of MRI, useful for the evaluation of loco-regional infiltration and lymph node involvement, the ratio of the short-to-long-axis diameter and the reader's diagnostic confidence for the presence of lymph node metastasis yielded accuracy of 84.8% and 86.9%, sensitivity of 86.7% and 87.5%, specificity of 81.3% and 86.2%, PPV of 89.7% and 87.5% and NPV of 76.5% and 86.2%, respectively. A long lymph node axis >10 mm and a short diameter >5.8 mm were found to be predictors of malignancy. At USG, instead, the two main characteristics of potentially malignant lymph nodes are cortical thickness and short axis length; the combination of these ultrasound parameters yielded the highest accuracy in distinguishing between negative and positive lymph nodes. Despite the heterogeneity of the included studies and the lack of randomized clinical trials, this review provides a broad overview of the three imaging tools used for the presurgical management of VSCC. Nowadays, although MRI and PET represent the gold standard, ultrasound evaluation is taking on a growing role, as long as it is carried out by expert sonographer. The management of this rare disease should be always performed by a multidisciplinary team in order to precisely stage the tumor and determine the most suitable treatment approach.

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.

Concurrent Chemo-radiotherapy in Anal Squamous Cell Carcinoma: A Retrospective Review of a Tertiary Centre Experience.

Anal cancer is a rare form of gastrointestinal malignancy, and treatment is often confined to specialist centres. It has a high cure rate with non-surgical approach resulting in organ preservation. The current accepted schedule is chemo-radiotherapy (CRT) with 5-fluorouracil and mitomycin with radiotherapy doses between 50.4 and 53.2 Gray in 28 fractions. This study included patients who had histological confirmation of squamous cell carcinoma and had completed the full CRT course for anal cancer between 2008 and 2018 in our centre. Data was collected retrospectively assessing demographics, staging, surgery, relapse, latest follow-up, date of death, CRT regimen and TNM stage. Outcome data and stoma reversal rate were analysed. Overall, 87 patients were included in the study. At diagnosis 94.3% of patients had T2-T4 disease, and 44.8% had involvement of positive loco-regional lymph nodes. Overall survival (OS) probability at 1, 3 and 5years were 98.8%, 87.4% and 83.7%, respectively. Results also revealed a statistically significant effect of time from diagnosis to the start of radiotherapy on OS (p = 0.039). Sixty-nine (79.3%) patients achieved complete remission at last follow-up. Twenty-one patients (24%) underwent surgery for a de-functioning stoma, and only five of these patients subsequently received stoma reversal surgery. Our data reflects the efficacy of CRT as the primary modality of treatment in the management of anal squamous cell carcinoma with effective organ preservation and disease control. Early stoma reversal may also enhance quality of life.

1634P Patterns of disease recurrence in relation to the extent of lymph node sampling in patients with resected lung carcinoid: A population-based study

In patients (pts) with resected pulmonary carcinoids, recurrence of disease may occur up to 10 years after surgery, but the exact incidence remains unknown. Locoregional lymph node (LN) involvement predicts poor prognosis. We evaluated recurrence-free interval (RFI) patterns in relation to the extent of surgical LN sampling.

Immunohistochemical Tumor Characteristics of Breast Cancer according to Participation in the Mammography Screening Program

Abstract Background Breast cancer detected in participants of the German Mammography Screening Program (MSP) shows a favorable distribution of prognostic parameters and hormone receptor status compared to cancer in non-participants, even including interval cancers. The aim of our study is to examine the distribution of intrinsic breast cancer subtypes considering the proliferation marker Ki-67 in participants and non-participants in a population-based setting and to evaluate the association between Ki-67 and tumour characteristics. Methods Population based data from the Epidemiological Cancer Registry Lower Saxony is analysed in this retrospectiv observational study. 1115 cases of breast cancer (in situ and invasive, year of diagnosis 2014) among women aged 50–69 years and residing in the regions of two screening units of Lower Saxony are included (n = 285 634 biennially entitled women). The group of the participants containes cancers that are detected by screening or in the interval of 24 month after a negative screening. The group of non-participants includes all breast cancers without match with screening data. Results Considering cases with invasive breast cancer (n = 953) tumours detected in screening participants are more often diagnosed in early T stage (T1, p < 0,0001), HER2 negativ (p = 0,0336), with lower Ki-67 percentage scores (p < 0,0003) and without loco-regional lymph node involvement (p < 0,0001), compared to tumours in non-participants – even including interval cancers. Regarding grading both groups show less differences (p = 0,1718), because interval cancer are more comparable with cancers in non-participants. We find distinct differences in distribution of the intrinsic suptypes between both groups (p < 0,0003): especially in category Luminal A (38,4 % vs. 26,7 %), but also in the categories Luminal A or B (26,7 vs. 22,1 %), Luminal B (21,1 vs. 30,6 %), HER2 enriched (5,1 vs. 7,8 %) und triple-negative (8,8 vs. 12,8 %). Ki-67 is associated with all analysed prognostic factors, first of all with grading (p < 0,0001). Discussion According to the S3-Guidelines an adjuvant chemotherapy can be avoided in the majority of Luminal A type breast cancers. Assuming that both groups received a guideline-based therapy MSP participants (including interval cancers) could be treated with less aggressive systemic therapy compared with cancers in non-participants. Our results indicate for both groups that Ki-67 is a prognostic marker, which is not independent of other histopathological factors.

Role of endoscopic ultrasound in esophageal cancer.

Esophageal cancer (ECA) affects 1 in 125 men and 1 in 417 for women and accounts for 2.6% of all cancer related deaths in the United States. The associated survival rate depends on the stage of the cancer at the time of diagnosis, making adequate work up and staging imperative. The 5-year survival rate for localized disease is 46.4%, regional disease is 25.6%, and distant/metastatic disease is 5.2%. Additionally, treatment is stage-dependent, making staging all that much important. For nonmetastatic transmural tumors (T3) and/or those that have locoregional lymph node involvement (N), neoadjuvant therapy is recommended. Conversely, for those who have earlier tumors, upfront surgical resection is reasonable. While positron emission tomography/computed tomography and other cross sectional imaging modalities are exceptional for detecting distant disease, they are inaccurate in staging locoregional disease. Endoscopic ultrasound (EUS) has played a key role in the locoregional (T and N) staging of newly diagnosed ECA and has an evolving role in restaging after neoadjuvant therapy. There is even data to support that the use of EUS facilitates proper triaging of patients and may ultimately save money by avoiding unnecessary or futile treatment. This manuscript will review the current role of EUS on staging and restaging of ECA.

Nonmetastatic ypt0 rectal cancer after neoadjuvant treatment and total mesorectal excision: Lessons from a retrospective multicentric cohort of 383 patients

BackgroundA better understanding of pathological features and oncological survival in ypT0 rectal cancer after neoadjuvant chemoradiotherapy is required to improve patient selection criteria for rectal-preserving approach by local excision. Our aim was to define risk of lymph node metastasis and oncological outcomes in ypT0 rectal cancer after chemoradiotherapy and total mesorectal excision. MethodsAll consecutive patients who underwent total mesorectal excision for a nonmetastatic rectal adenocarcinoma classified ypT0 after neoadjuvant chemoradiotherapy, with or without locoregional lymph node involvement (ypN+ or ypN-), in 14 French academic centers between 2002 and 2015 were included. Data were collected retrospectively. Overall and disease-free survival were explored. ResultsAmong the 383 ypT0 patients, 6% were ypN+ (23/283). Before chemoradiotherapy, 86% (327/380) were staged cT3-T4 and 41% (156/378) were staged cN+. The risk of ypN+ did not differ between cT3-T4 and cT1-T2 patients (P = .345) or between cN+ and cN- patients (P = .384). After a median follow-up of 61.1 months, we observed 95% confidence interval (92%–97%) of 5-year overall survival and 93% confidence interval (91%–96%) of 5-year disease-free survival. In Cox multivariate analysis, overall survival was altered by intra-abdominal septic complications (hazard ratio = 2.53, confidence interval [1.11–5.78], P = .028). Regarding disease-free survival, ypN+ status and administration of adjuvant chemotherapy were associated with a reduced disease-free survival (P = .001 for both). cT3/T4 staging and cN+ staging did not modify overall survival (P = .332 and P = .450) nor disease-free survival (P = .862 and P = .124). ConclusionThe risk of lymph node metastasis and the oncological survival do not depend on the initial cT or cN staging in cases of ypT0 complete rectal tumor regression.

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.

Overlapping but Distinct Risk Factors Between Recurrent Follicular and Recurrent Papillary Thyroid Carcinomas

Overlapping but Distinct Risk Factors Between Recurrent Follicular and Recurrent Papillary Thyroid Carcinomas

P-20 Concurrent chemo-radiotherapy in anal squamous cell carcinomas: A 10-year retrospective review of a tertiary centre experience

Anal cancer is an uncommon form of gastrointestinal malignancy and treatment is often confined to specialist centres. It has a high cure rate with a non-surgical approach resulting in organ preservation. Chemo-radiotherapy (CCRT) remains the standard treatment for these cancers. The current accepted schedule is CCRT with 5FU mitomycin C (5FUMC) and radiotherapy doses between 50.4-53.2 Gray in 28 fractions. This study included patients who had histological confirmation of squamous cell carcinoma and had completed the full CCRT course in our centre for anal cancer between 2008 and 2017. The concurrent chemotherapy was mitomycin C with either 5FU or capecitabine. Some patients received neoadjuvant chemotherapy and some had adjuvant chemotherapy. Data was collected retrospectively assessing basic demographics, staging, surgery, relapse, latest follow-up, and date of death, as well as CCRT regimen. All TNM stages were included and original staging was revised on review of imaging based on TNM 8th edition. Outcome data and stoma reversal rate were analysed. Overall, 87 patients were included in the study. The median age of patients was 60 years. At diagnosis, 94.3% of patients had T2-T4 disease and 44.8% had involvement of positive loco-regional lymph nodes. Overall survival (OS) probability at 1, 3, and 5 years were 98.8%, 87.4%, and 83.7%, respectively. Results also revealed a statistically significant effect of time from diagnosis to radiotherapy start on OS (p=0.039). Sixty-nine (79.3%) patients achieved complete remission at last follow-up. Three (3.4%) patients had a local relapse and 9 (10.3%) relapsed systemically. Six patients (6.9%) had persistent disease. The mean time to relapse was 16 months, and Median OS was 52.3 months. Twenty-one patients (24%) underwent surgery for a defunctioning stoma, only five of these patients subsequently received stoma reversal. Our data reflects the efficacy of CCRT as the primary modality of treatment in the management of anal squamous cell carcinoma with effective organ preservation and disease control. Further studies with increased dose to primary may improve outcomes even further. Early stoma reversal would also improve quality of life.

Mantle Cell Lymphoma Mimicking Mucosa-Associated Lymphoid Tissue (MALT) Lymphomas: A Pathological Characterization (on behalf of the “Fondazione Italiana Linfomi (FIL) - Postgraduate Master Course”)

INTRODUCTION: Mantle Cell Lymphoma (MCL) is considered an aggressive B-cell lymphoma, but with a heterogeneous outcome and a median overall survival ranging from 3 to 5 years (yrs). Two different subsets are recognized, known as “classical” and “leukemic non-nodal” subtypes. Unfrequently MCL presents with isolated extranodal localization mimicking mucosa-associated lymphoid tissue (MALT) lymphomas; a large series of European Mantle Cell Network has been recently reported (Morello et al, ICML 2017). On the other side, pathological features of this peculiar presentation are not yet clarified.METHODS: We collected data on 34 patients (pts) with extranodal mantle cell lymphoma (EMCL) of MALT site, diagnosed between 2001 and 2016 in 10 Italian Centers of Fondazione Italiana Linfomi (FIL) network. The diagnosis of MCL was confirmed through detection of CyclinD1 overexpression and/or t(11;14). All pts were >18 yrs and HIV negative. Only minimal locoregional nodal involvement, with CT longest axis <2 cm, and bone marrow involvement with only extranodal disease were allowed. Pts with splenomegaly and leukemic disease were excluded. We performed a central pathological review of 21/34 cases (62%) in the Section of Anatomic Pathology of University of Pavia and compared their features with a cohort of nodal MCL.RESULTS: Clinical features and treatments are summarised in Table 1.Biopsied extranodal sites were as follows: 11 pts (32%) Waldeyer's ring, 11 (32%) gastrointestinal tract, 3 (9%) ocular adnexa, 3 (9%) oral cavity, 3 (9%) salivary glands, 2 (6%) thyroid and 1 (3%) liver. Detailed morphology was assessed in 28 pts: classical in 22 pts (78%), pleomorphic in 3 (11%) and blastoid in 3 (11%). CD5 expression was performed in 31 cases: 21 (68%) positive, 6 (19%) partially positive and 4 (13%) negative. Median Mib1/Ki67 was low (15%, range: 2-70%), <30% in 83% and ≥30% in 17% cases. CyclinD1 was available in 33 pts (88% positive, 3% negative, 9% partially positive) and t(11:14) in 13 pts (92% positive). SOX11 staining was performed in 21 cases: 17 (81%) resulted positive, 3 (14%) partially positive and only 1 (5%) negative. Overall, no statistically significant difference with nodal MCL series was observed, particularly regarding cytological features, CD5 and SOX11 expression and Mib1/Ki67. MIPI score was calculated in 33 pts: 15 (46%) low, 13 (39%) intermediate and 5 (15%) high; biologic-MIPI score was available in 29 pts: 7 (24%) low, 14 (48%) intermediate and 8 (28%) high.After a median follow-up of 5.1 yrs (0.5-15), overall survival (OS) was 93% at 5 yrs and 75% at 10 yrs with 4 deaths (2 for lymphoma, 2 for unknown cause). All the 12 pts treated with autologous stem cell transplantation was still alive at last follow-up. Progression-free survival (PFS) was 74% after 5 yrs and 64% after 10 yrs of follow-up. Univariate analysis results are overlapping with European series: pts with age <65 yrs (p=0.002), ECOG 0 (p=0.012), low MIPI score (p=0.005) and low biologic MIPI score (p=0.008) had a longer OS. In univariate analysis, a longer PFS was observed in pts with age <65 yrs (p=0.016), ECOG 0 (p=0.002), low MIPI score (p<0.001) and low biologic MIPI score (p=0.011). In multivariate analysis, age (p=0.022) confirmed its impact on PFS, after adjusting for biologic MIPI score.CONCLUSIONS: According to our preliminary data, we define EMCL as a subset with preferential involvement of Waldeyer's ring and gastrointestinal tract, mimicking the clinic-pathologic features of marginal zone lymphoma of extranodal sites, from which it should be differentiated via a thorough histologic characterization, and featuring the indolent course of the indolent variant of MCL. On the other hand, our cases harbored the morphologic and phenotypic features of the nodal form of MCL. On the basis, the true nature of this putative MCL subset should be deepened upon biologic characterization, including mutational and IGVH status analysis. [Display omitted] DisclosuresLoseto:gilead: Membership on an entity's Board of Directors or advisory committees; janssen: Consultancy; italfarmaco: Membership on an entity's Board of Directors or advisory committees. Arcaini:Pfizer: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sandoz: Consultancy; Gilead: Research Funding. Zaja:Novartis: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Abbvie: Honoraria; Takeda: Honoraria; Gilead: Honoraria; Janssem: Honoraria; Celgene: Honoraria, Research Funding.

Abstract PS4-27: A prospective multicenter study evaluating the impact of the 21-Gene Breast Recurrence Score® upon physician treatment decision and cost in lymph node-positive breast cancer patients in Quebec

Abstract Background: Locoregional lymph node involvement has historically been used as the most important deciding factor for the administration of chemotherapy in the adjuvant setting of breast cancer patients. The 21-gene Breast Recurrence Score® assay (the assay) is emerging as an important tool to assist with chemotherapy decisions amongst hormone receptor (HR)-positive, node-positive breast cancer (BC) patients. Previous studies have suggested that node-positive patients with low Recurrence Score (RS) results do not benefit from chemotherapy. We wanted to better understand the impact of the assay upon physician treatment decisions and treatment cost in this patient cohort. Methods: We conducted a multicenter prospective observational trial for ER/PR-positive HER2-negative BC patients that have undergone surgical treatment for T1-T3 disease and 1-3 positive lymph nodes. Physicians were required to complete a questionnaire indicating treatment choice prior to and post availability of Recurrence Score results. Patients were enrolled in the study from the time of consent to 6 months after the start of adjuvant therapy. The primary endpoint was change in the physician’s recommendation for chemotherapy prior to and post assay results. Secondary endpoints include the change in recommendation for additional growth factor (GF) supportive therapy, change in physician’s expressed level of confidence, and changes in estimated cost of recommended treatments prior to and post assay results. Results: 70 patients were enrolled between March 2018 and September 2019 at five hospital centers, as part of the McPeak Sirois Group of Quebec. The median age of the cohort was 61 years (range, 38 to 82 years). 18.5% (n=13) of the cohort consisted of patients &amp;lt; 50 years, and 81.4% (n=57) were &amp;gt; or = to 50 years. 64.3% (n=45) of the patients had one positive lymph node and 35.7% (n=25) of the patients had 2 or 3 positive lymph nodes. 25.7% (n=18) of the patients had a RS &amp;lt; 11 and 68.6% (n=48) had a RS result between 11-25. For the entire cohort, we found that the proportion of patients for whom chemo-hormonal therapy was recommended was reduced by an absolute 67.1% by knowledge of the RS result (OR (odds of having chemo-hormonal therapy post-RS recommendation versus pre-RS recommendation) = 0.03 [95% CI: 0.01-0.08]; P&amp;lt;0.0001). The RS results led to an absolute reduction in physician recommendation in chemo-hormonal therapy by 38.5% for patients &amp;lt; 50 years, and by 73.7% of patients (OR=0.02 [95% CI: 0.01-0.06]; P &amp;lt;0.0001) for patients &amp;gt; or = to 50 years. Changes in treatment recommendation were identified for patients with one positive node, 73.3% (OR=0.02 [95% CI: 0.01-0.07]; P&amp;lt;0.0001); and for patients with two or three positive nodes, 56.0% (OR=0.06 [95% CI: 0.02-0.23]; P&amp;lt;0.0001). Recommendations for GF supportive therapy due to RS results decreased by 42.6% (OR=0.16 [95% CI: 0.07-0.34]; P &amp;lt;0.0001). Moreover, RS results led to an increase in confidence in physician treatment decisions for 68.6% of patients (OR=18.3 [95% CI: 7.90-42.28]; P &amp;lt;0.0001). We found that the cost of chemotherapy, in addition to anti-emetics and GF supportive therapy, decreased by 69.9% per patient (pre-RS mean, $3,968 CAN; versus post-RS mean, $1,196 CAN) (P &amp;lt;0.0001). Conclusions: Overall, we found that the 21-gene Breast Recurrence Score® assay changed physician treatment decisions in about two-thirds of all patients with hormone receptor-positive, node-positive BC, regardless of the number of positive nodes (up to 3). The assay increased physician confidence and was associated with an important decrease in treatment cost. Taken together, the assay is a cost-effective approach that can decrease the use of chemotherapy amongst HR-positive, node-positive BC patients in Quebec. Citation Format: Saima Hassan, Rami Younan, Erica Patocskai, Louise Provencher, Brigitte Poirier, Lucas Sideris, Pierre Dubé, Jean-Francois Boileau, Catalin Mihalcioiu, André Robidoux. A prospective multicenter study evaluating the impact of the 21-Gene Breast Recurrence Score® upon physician treatment decision and cost in lymph node-positive breast cancer patients in Quebec [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-27.

Modified Inguinal Lymph Node Dissection in Groin-Negative Patients of Penile Cancer: Our Experience.

Cancer of the penis is an important health problem in India, causing significant morbidity. Involvement of locoregional lymph nodes is the most significant prognostic factor for patients with penile cancer. In this study, we reviewed clinical data of all patients who underwent modified inguinal lymph node dissection as a means to diagnose micro-metastasis in inguinal lymph nodes, and analysed the outcomes. We retrospectively reviewed the hospital clinical charts of patients treated for carcinoma of the penis. Inguinal and distant metastases were assessed by physical examination, ultrasound imaging of the inguinal region, computed tomography of the abdomen and pelvis and a chest radiograph. Patients with clinically negative inguinal lymph nodes underwent modified lymph node dissection (mILND) both to diagnose and stage the disease. Complications occurring during a 30-day period after surgery were defined as early and thereafter as late complications. A total of 40 patients with a mean age of 52.27±13.10 (range 25-73) years underwent mILND. Wedge biopsy from the primary lesion had revealed intermediate-risk disease in 22 (55%) patients and high-risk disease in 18 (45%) patients. Histopathological examination of the primary penile lesion revealed a pT1 lesion in 32 patients and a pT2 lesion in the remaining 8 patients. Fourteen (35%) of the 40 patients showed micro-metastases in the inguinal lymph nodes on frozen sections. The mean follow-up in these patients was 56.6±18.09months. There were no instances of local or systemic recurrences seen in 38 (95%) patients within 5years. Superficial lymph node dissection and where facilities are available DSLNB remain the standard of care in the management of patients with clinically groin-negative (cN0) intermediate- and high-risk groups. Modified inguinal lymph node dissection would be a safe and appropriate alternative to this in all centres that do not have access to newer modalities like DSLNB, video-endoscopic (VEIL) or robotic-assisted techniques.

Clinical and genetic risk factors define two risk groups of extracranial malignant rhabdoid tumours (eMRT/RTK).

Extracranial rhabdoid tumours are rare, highly aggressive malignancies primarily affecting young children. The EU-RHAB registry was initiated in 2009 to prospectively collect data of rhabdoid tumour patients treated according to the EU-RHAB therapeutic framework. We evaluated 100 patients recruited within EU-RHAB (2009-2018). Tumours and matching blood samples were examined for SMARCB1 mutations by sequencing and cytogenetics. A total of 70 patients presented with extracranial, extrarenal tumours (eMRT) and 30 with renal rhabdoid tumours (RTK). Nine patients demonstrated synchronous tumours. Distant metastases at diagnosis (M+) were present in 35% (35/100), localised disease (M0) with(LN+) and without (LN-) loco-regional lymph node involvement in 65% (65/100). SMARCB1 germline mutations (GLM) were detected in 21% (17/81 evaluable) of patients. The 5-year overallsurvival (OS) and event-free survival (EFS) rates were 45.8±5.4% and 35.2±5.1%, respectively. On univariate analyses, age at diagnosis (≥12 months), M0-stage, absence of synchronous tumours, absence of a GLM, gross total resection (GTR), radiotherapy and achieving a CR were significantly associated with favourable outcomes. In an adjusted multivariate model presence of a GLM, M+ and lack of a GTR were the strongest significant negative predictors of outcome. We suggest to stratify patients with localised disease (M0), GTR+ and without proof of a GLM (5-year OS 72.2±9.9%) as 'standard risk'. Patients presenting with one of the features M+ and/or GTR- and/or GLM+ belong to a high risk group (5-year, OS 32.5±6.2%). These patients need novel therapeutic strategies such as combinations of targeted agents with conventional chemotherapy or novel experimental approaches ideally within international phase I/II trials.

Conjunctival Melanoma: Outcomes Based on Age at Presentation in 629 Patients at a Single Ocular Oncology Center

To investigate the clinical features and outcomes for conjunctival melanoma based on patient age. A retrospective review of patients with conjunctival melanoma managed at a single tertiary referral center from April 18, 1974, to September 9, 2019. Clinical features and outcomes were compared by patient age category at presentation (young ≤45 years, middle-aged 46-69 years, and older ≥70 years), with Kaplan-Meier and Cox proportional hazard analysis [hazard ratio (95% confidence interval)]. There were 629 patients categorized as young in 130 (21%), middle-aged in 278 (44%), and older in 221 (35%). A comparison by age category (young vs. middle-aged vs. older) revealed that older patients had melanoma with greater number of affected quadrants (1.7 vs. 1.8 vs. 2.0, P = 0.001) and clock hours (3.9 vs. 4.2 vs. 5.2, P = 0.001). All patients were treated with surgical excision, with no difference in requirement for additional medical or radiation therapy. By 10-year Kaplan-Meier outcomes, older patients had more frequent visual acuity loss ≥3 lines (11% vs. 28% vs. 64%, P < 0.001) and local tumor recurrence (38% vs. 46% vs. 70%, P < 0.001). Hazard ratio for the oldest age group (age ≥70) revealed a 7.76-fold (3.33-18.09) increased risk for visual acuity loss (P < 0.001), and a 2.08-fold (1.32-3.28) increased risk of local tumor recurrence (P = 0.002). There was no difference by age in risk for enucleation, exenteration, locoregional lymph node involvement, distant systemic metastasis, or death. Older patients with conjunctival melanoma present with more extensive disease and have increased risk for visual acuity loss and local tumor recurrence.

RTOG 3506 (STEEL): A study of salvage radiotherapy with or without enzalutamide in recurrent prostate cancer following surgery.

TPS5601 Background: Salvage radiotherapy (SRT) is an important intervention for men with prostate cancer (PCa) who experience biochemical recurrence (BCR) after radical prostatectomy (RP). These patients are in need of cure or else they will develop metastatic disease. NRG/RTOG 9601 (WU Shipley, N Eng J Med 2017) identified a survival benefit from the addition of androgen receptor (AR) inhibition to SRT that was most prominent in men with high-risk features. Enzalutamide (Enza) is a non-steroidal anti-androgen that improves survival in castration-resistant and -sensitive PCa. We hypothesized that enhanced AR suppression with Enza would augment the benefit of SRT + androgen deprivation therapy (ADT) in BCR with high risk features. Methods: RTOG 3506 (STEEL, NCT03809000) is a randomized phase II study of SRT in BCR after RP with a serum PSA ≥ 0.2 ng/mL active in the USA and Canada. Patients are stratified by number of high-risk features including Gleason score (8-10), locoregional node involvement at RP, seminal vesicle invasion, persistently elevated PSA after RP, and PSA &gt; 0.7 ng/mL. All patients receive SRT with 2 years of ADT. The experimental arm also receives Enza 160 mg daily for 2 years. Patients are followed by PSA every 3 months. SRT can be highly individualized per treating physician beyond the mandatory treatment of the prostatic fossa. Treatment of the pelvis and/or para-aortic nodes, as well as sequential or concurrent boosts to a prostatic fossa mass and/or suspicious lymph nodes, are allowed options. This permits individualization of radiotherapy guided by CT, MRI, PET, and/or biopsy findings. The primary goal of this study is to determine whether SRT enhanced ADT with Enza, will improve progression-free survival (PFS) compared to SRT with standard ADT. PFS defined as the first occurrence of biochemical failure, clinical failure, or initiation of new anticancer treatment. STEEL is designed to demonstrate a 35% reduction in the risk of progression at 5 years. An accrual goal of 242 patients will provide 80% power with a one-sided alpha = 0.10. Secondary endpoints include disease control rates, acute and late physician- and patient-reported toxicity, and quality of life. This study was activated in February 2019. Site recruitment and activation are underway. Conclusions: There is an unmet and urgent need for individualized strategies to optimize systemic therapy used with SRT for men with BCR. Outcomes from this study will further clarify the approach to systemic therapy for SRT in high-risk BCR patients. Support: Provided by Pfizer. Clinical trial information: NCT03809000 .

Isolated Mandibular Metastasis Detected on Staging 18FDG PET/CT Scan in a Case of Carcinoma Urinary Bladder.

Isolated mandibular metastasis is very rare from carcinoma urinary bladder with no locoregional lymph node involvement. Here, we present a case where staging fluorodeoxyglucose - positron emission tomography - computed tomography (FDG PET-CT) scan showed an FDG avid primary lesion in carcinoma urinary bladder with FDG avid erosion in the right mandibular condyle. However, since no pelvic lymph nodes were involved, the mandibular lesion was kept on follow-up and cystoprostatectomy was performed. Follow-up FDG PET-CT scan after 6 months revealed an osteolytic destructive lesion in the mandible with associated soft tissue component and the biopsy confirmed this as metastatic lesion.

Prostate-Specific Membrane Antigen Ligand Positron Emission Tomography in Men with Nonmetastatic Castration-Resistant Prostate Cancer.

Systemic androgen-signaling inhibition added to ongoing androgen-deprivation therapy (ADT) improved clinical outcomes in patients with nonmetastatic castration-resistant prostate cancer without detectable metastases by conventional imaging (nmCRPC). Prostate-specific membrane antigen ligand positron emission tomography (PSMA-PET) detects prostate cancer with superior sensitivity to conventional imaging, but its performance in nmCRPC remains largely unknown. We characterized cancer burden in high-risk patients with nmCRPC using PSMA-PET. We retrospectively included 200 patients with nmCRPC, prostate-specific antigen (PSA) >2 ng/mL, and high risk for metastatic disease [PSA doubling time (PSADT) of ≤10 months and/or Gleason score of ≥8] from six high-volume PET centers. We centrally reviewed PSMA-PET detection rate for pelvic disease and distant metastases (M1). We further evaluated SPARTAN patients stratified by risk factors for PSMA-PET-detected M1 disease. PSMA-PET was positive in 196 of 200 patients. Overall, 44% had pelvic diseases, including 24% with local prostate bed recurrence, and 55% had M1 disease despite negative conventional imaging. Interobserver agreement was very high (κ: 0.81-0.91). PSA ≥ 5.5 ng/mL, locoregional nodal involvement determined by pathology (pN1), prior primary radiation, and prior salvage radiotherapy independently predicted M1 disease (all P < 0.05). PSMA-PET detected any disease in nearly all patients and M1 disease in 55% of patients previously diagnosed with nmCRPC, including subgroups with PSADT of ≤10 months and Gleason score of ≥8. The value of PSMA-PET imaging for treatment guidance should be tested in future studies.

2155 A Minimally Invasive Approach to Resection of a Duodenal Neuroendocrine Tumor Using the Full-Thickness Resection Device

INTRODUCTION: The Full-Thickness Resection Device (FTRD) allows for diagnostic and therapeutic endoscopic full-thickness resection (EFTR) of lesions that are unresectable with conventional endoscopic techniques. The device offers a minimally invasive approach to full thickness resection of intestinal and rectal lesions, and ensures safe tissue closure with over-the-scope-clip (OTSC) technology. We report a patient in whom the FTRD system was used for R0 resection of a duodenal neuroendocrine tumor. CASE DESCRIPTION/METHODS: A 68 year-old-male with history of Barrett’s esophagus was found to have a low-grade neuroendocrine tumor of the duodenal bulb on surveillance upper endoscopic screening. Computed tomography (CT) imaging of the abdomen revealed a hypervascular duodenal bulb mass, without obvious extension to the wall, lymphadenopathy, or evidence of metastasis. Endoscopic ultrasound (EUS) with fine needle aspiration (FNA), revealed a 1.2 cm mass arising from the submucosal layer with pathology indicating a low-grade neuroendocrine tumor. Due to the small tumor size, EFTR by FTRD was planned. Upon advancing the endoscope with the FTRD system attached, a non-bleeding neuroendocrine tumor was visualized (Figure 1). The mass was carefully pulled into the cap and after banding, ligation and cutting; there was a full thickness en bloc resection with all layers of the duodenum apparent (Figure 2). Pathology of the specimen documented a grade 2 neuroendocrine tumor with clean margins, confirming R0 resection (Figure 3). The patient was discharged the same day without associated complications. DISCUSSION: Upper gastrointestinal endoscopy and histologic examination are essential for diagnosis of duodenal neuroendocrine tumors, and EUS should follow for determination of size and depth of infiltration as well as determination of locoregional lymph node involvement. Multiple factors, such as tumor size, location, and grade need to be considered when determining treatment options. The FTRD system offers a novel endoscopic treatment approach to tumors extending beyond the submucosa that require full thickness resection and would otherwise require higher risk surgical intervention. The technology allows for safe tissue closure, valid histologic evaluation of the en-bloc specimen, and minimal thermal injury, thus reducing the morbidity and cost otherwise associated with surgery. Our case illustrates the successful R0 resection of a T2, grade 2 neuroendocrine tumor using the FTRD.

Clinical and molecular determinants of extrahepatic disease progression in patients with metastatic colorectal cancer with liver-limited metastases deemed initially unresectable

BackgroundNo tools to predict the probability of extrahepatic disease progression (ePD) of initially unresectable, liver-limited metastatic colorectal cancer (mCRC) are currently available. To estimate the likelihood to develop ePD and to identify clinical and molecular factors that could predict extrahepatic progression-free survival (ePFS), we conducted an observational, retrospective, multicentre cohort study.MethodsWe retrospectively identified a cohort of 225 patients with initially unresectable liver-limited disease (LLD), treated from January 2004 to December 2017 with first-line doublets or triplet plus a biological agent at two Italian institutions.Results173 (77%) patients experienced ePD which occurred within 1, 2 or 3 years from the diagnosis of mCRC in 15%, 49% and 66% of patients, respectively. Globally, 164 (73%) patients underwent a liver resection at some point of their disease history, and 54 (33%) of them underwent a subsequent locoregional treatment. Age > 70 years, locoregional nodal involvement at diagnosis of colorectal cancer and ≥4 liver metastases were significantly associated with higher risk of ePD while liver resections were associated with reduced risk of ePD. In the multivariable model, number of liver metastases (subdistribution HR, SHR 1.63, 95% CI 1.12 to 2.36; p = 0.01) and liver resections (SHR 0.43, 95% CI 0.29 to 0.63; p = 0.001) were still associated with ePD. Number of liver metastases < 4, no nodal involvement at diagnosis and liver resections were also associated with prolonged ePFS.ConclusionsThe identified clinical factors could help physicians in personalising the intensity and aggressiveness of liver-directed treatments in patients with mCRC with initially unresectable LLD.