Evidence Of Residual Tumor Research Articles

Real‑world retrospective study of early‑stage prostate cancer at a Portuguese Comprehensive Cancer Centre: The PEarlC study.

Despite the high prevalence of localised prostate cancer (LPC) and locally advanced prostate cancer (LAPC), evidence on the characteristics of patients, treatments and clinical outcomes stratified by disease risk is limited. The PEarlC study was conducted to characterise a cohort of patients with early-stage prostate cancer that included real-world clinical outcomes. Retrospective data from a cohort of patients diagnosed with LPC/LAPC between 2015 and 2017 and followed up until December 2020 at a Portuguese comprehensive cancer centre (IPO Porto) was analysed. Patients were classified as LPC (high- or non-high-risk) or LAPC according to European Association of Urology guidelines, were eligible if diagnosed at stage I-III and followed up in Urology, Medical Oncology or Radiation Oncology outpatient clinics of IPO Porto. Data was collected from the medical/administrative records database. Clinical outcomes included prostate-specific antigen (PSA) progression-free survival, metastasis-free survival, disease-free survival, progression-free survival, overall survival (OS), PSA response (palliative) and no evidence of residual tumour (prostatectomy). Time-to-event outcomes were compared between subgroups using the log-rank test. A total of 790 patients were included (54.8% non-high-risk LPC, 30.9% high-risk LPC, 14.3% LAPC) and the median follow-up was 46.7 months. Patients had a median age of 68.0 years. The majority of patients were stage II (52.9%) and Eastern Cooperative Oncology Group 0-1 (99.9%) and received treatment with curative intent (85.4%). The median was only achieved in progression-free survival (29.9 months; 95% CI, 26.5-41.0 months), as evaluated in palliative patients. At year 5, 82.9% were free of PSA progression (curative), 87.5% were metastasis-free, 83.7% were disease-free, all patients in palliative treatment progressed and the 5-year OS rate was 92.9% (CI 95%, 90.2-95.7%). Among patients with LPC, OS was worse in high-risk vs. non-high-risk patients (5-year OS rate, 88.8% vs. 96.8%; hazard ratio=3.34, CI 95%, 1.64-7.05; P=0.001). PSA response rate was 81.4% in the palliative setting. There was no evidence of residual tumour in 61.6% of patients who underwent prostatectomy. Although most patients with early-stage prostate cancer treated at IPO Porto showed positive 5-year real-world outcomes, patients with high-risk LPC showed worse OS compared with patients with non-high-risk LPC and therefore a poorer prognosis. The present large-sample real-world study is an important contribution to reducing the evidence gap on prostate cancer.

Varnishing prostate cancer acinar (adenocarcinoma of the prostate gland pt0) in prostate biopsy specimen which subsequently becomes diagnosed as no prostate cancer or pt0 prostate cancer in a prostatectomy specimen: review and update

Taking into consideration the increased undertaking of screening tests for serum prostate-specific antigen (PSA), it would be envisaged that the diagnosis of prostate cancer at an early clinical stage and small tumour-size had been appreciably increased over recent years and as a consequence, the volume of tumour within radical prostatectomy (RP) specimens had decreased in size. Pathological stage pT0 is referred to as no evidence of residual tumour within a radical prostatectomy (RP) specimen from a patient in whom biopsy-proven prostate carcinoma had been histologically confirmed as a diagnosis. This entity was given a terminology of the "vanishing cancer phenomenon" by Goldstein and associates. The pT0 stage of prostate cancer had been noted ensuing hormone therapy or prior transurethral resection of the prostate (TURP) for benign prostatic hyperplasia before the undertaking of RP. Even though much research had addressed these two scenarios of pT0 stage prostate cancer, patients that manifest with pT0 status in cases other than the aforementioned two scenarios occur on very rare occasions which had been iterated to be in between 0.2% and 0.8% of all prostate cancer patients). Only few studies had examined such patients. The clinical significance of pT0 staging has remained not to be clear. Nevertheless, many reports had documented that that pT0 stage patients do portend a highly satisfactory clinical outcome. pT0 at RP is extremely rare. Although most pT0 patients had tended to have low serum PSA levels, low clinical stage, low biopsy Gleasson Score (GS), and only one positive biopsy core, those with more aggressive characteristics could still harbour pT0 at RP. In order to prevent the undertaking of unnecessary treatment of such clinically insignificant cancers, it would be important to ascertain preoperative clinical and pathologic characteristics which might help the Urologists and oncologist to pre-operatively ascertain patients with a high probability of pT0 staging upon RP specimens. The ensuing article has discussed general overview aspects as well as miscellaneous narrations and discussions from some case reports, case series and studies related to the varnishing prostate cancer in order to provide recent educative material on the varnishing prostate cancer to all readers.

Impact of an in-consult patient decision aid on treatment choices and outcomes of management for patients with an endoscopically resected malignant colorectal polyp: a study protocol for a non-randomised clinical phase II study

IntroductionManagement of an endoscopically resected malignant colorectal polyps can be challenging due to the risk of residual tumour and lymphatic spread. International studies have shown, that of those choosing surgical...

THU023 Sparse Granulation In Growth Hormone Secreting Adenomas: Clinical Implications Of A Rare Histological Finding

Abstract Disclosure: A. Merrill: None. R. Varughese: None. G. Campbell: None. L. Belalcazar: None. Introduction: Acromegaly is an uncommon disease. Endocrinologists may be unfamiliar with the clinical implications of granularity findings on the histology of growth hormone (GH)-secreting adenomas. We present the case of a patient with acromegaly in whom a sparsely granulated (SG) histological subtype was identified post-operatively. We discuss the clinical presentation and therapeutic implications of this finding. Case Presentation: A 36-year-old man was admitted to the hospital with rectal bleeding and incidentally found to have features consistent with acromegaly. Patient reported that over 1 year he had noticed changes in his facial features, enlargement of his hands and had developed hand and knee arthralgias. During the 6 months prior to admission, he experienced worsening fatigue, but denied severe headaches or vision changes. Past medical history was significant for osteosarcoma as a young child treated with an above the knee amputation. Family history was negative for pituitary tumors or colon cancer. Physical exam revealed a blood pressure of 104/53 mmHg and an amputation-adjusted body mass index of 27.4 _kg/ m2 . He had mild frontal bossing, enlarged nose, macroglossia, swollen hands and foot. Rectal examination revealed hemorrhoids but no masses. Gross visual field deficits were identified at bedside. Laboratory findings were significant for an elevated IGF-1 at 975 ng/mL (83-240 ng/mL) and GH 45.2 ng/mL (0.3-9 ng/mL). Patient was also found to have panhypopituitarism: TSH 1.54 mIU/L (0.45-4.70 mIU/L), Free T4 0.62 ng/dl (0.78 - 2.20 ng/dL); ACTH 13.3 pg/ml (7.2 - 63.3 pg/mL), cortisol AM 3.6 ug/dL (4.5-23.0 ug/dL), peak cortisol after ACTH stimulation 16.0 ug/dL; testosterone 31.6 ng/dl (132-813 ng/dL), LH 1.75 mIU/ml (1.2-8.6 mIU/mL). His hemoglobin A1c was 5.7%. MRI of the brain revealed a large enhancing lobulated sellar/suprasellar lesion of 5.0 x 2.4 x 2.8 cm, with extension to the third ventricle and mass effect on the optic chiasm. Patient underwent partial surgical resection of the large tumor. Pathology identified a SG somatotroph tumor with most cells being negative or weakly positive for GH on immunohistochemical staining. TSH, prolactin, and ACTH stains were negative. There was evidence of residual tumor, which was located superiorly, not accessible through the transsphenoidal route.A colonoscopy and formal visual field testing are pending currently. Patient is waiting for a second surgery via craniotomy and, given the SG finding on histology, pasireotide therapy will be offered. Discussion: The sparsely granulated (SG) subtype is an uncommon variant of GH-producing. Our patient illustrates the aggressive nature of SG GH-producing adenomas. These tumors express more invasive growth and resistance to standard somatostatin analogue therapy. There is a growing recognition that adenoma granulation is an important consideration in the management of acromegaly. Presentation: Thursday, June 15, 2023

Abstract 820: Photo-activatable ON-OFF microparticles for on-demand pulsatile drug delivery in a breast cancer model

Abstract The ability to treat tumors with high efficacy in a local microenvironment, while mitigating the side effects of systemic toxicity is an area of active investigation. Towards this goal, designing a minimally-invasive local therapeutic modality, with a controlled, pulsatile drug release mechanism is an attractive proposition. In this study, a near-infrared (NIR) photo-activatable microparticle was developed for localized, pulsatile delivery of encapsulated anticancer drugs into the tumor with simultaneous thermal ablation, with controlled ON-OFF thermal cycles using NIR laser irradiation. The microparticles were fabricated using a poly(caprolactone) (PCL) matrix, containing 2D molybdenum disulfide (MoS2) nanosheets as the NIR-responsive photothermal agent, and doxorubicin or violacein, as hydrophilic and hydrophobic model anticancer drugs, respectively. Cubic microparticles of 200 µm size were fabricated by casting a polymer-MoS2-drug film on PDMS mold with loading efficiency of 2 μg MoS2 per particle, and 0.2-8 μg of drug per particle. A cytotoxicity assay was performed to test the efficacy of the loaded microparticles in reducing the viability of 4T1 murine-derived cell culture, using the ON-OFF laser switch mechanism. In order to select a suitable laser power and duration of treatment for in vivo studies, a Machine Learning algorithm based on a Random Forest classifier was trained, to arrive at the optimal treatment conditions: 0.4-0.5 W/cm2 of laser power at 808 nm, for 3 cumulative minutes of laser irradiation, to reach the target temperature of 50 °C, which activates PCL melting and subsequent drug release. The effect of pulsatile treatment was studied in vivo in a murine-derived 4T1 subcutaneous mouse model of breast cancer, using this photo-activatable ON-OFF switch mechanism, for up to 3 cycles of laser irradiation. As control groups, tumor only (no treatment), laser only (no drug or microparticle), drug only (no laser or microparticle), microparticles only (no drug or laser), and microparticles with laser (no drug) were studied. The cohorts receiving the photo-activated 3-cyclic treatment for both drugs showed increased median survival up to 40 days post tumor induction, compared to a median survival of 16 days for the control groups. Although one laser cycle was enough to trigger drug release, there was a significant shrinkage in the tumor volume noticed with 3 cycles, with eventual scarring and shedding of the tissue with no evidence of residual tumor at the primary site. While this cyclic drug release modality is very effective at treating the primary site, subsequent histopathology revealed that the aggressive tumor in some animals had metastasized to the liver and other organs. More work is ongoing to design better targeted approaches to deliver the drug-loaded microparticles to the site of metastatic tumors, to increase the survival prospects of this disease. Citation Format: Maria Kanelli, Neelkanth M. Bardhan, Morteza Sarmadi, Shahad Alsaiari, William Rothwell, Apurva Pardeshi, Angela M. Belcher, Ana Jaklenec, Robert S. Langer. Photo-activatable ON-OFF microparticles for on-demand pulsatile drug delivery in a breast cancer model [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 820.

PD13-07 MULTIPARAMETRIC MRI OF THE BLADDER AS A PREDICTIVE FACTOR OF HISTOPATHOLOGY AT RETUR IN T1GH WITH PRESENCE OF DETRUSOR MUSCLE: COULD IT HAVE A ROLE?

You have accessJournal of UrologyCME1 Apr 2023PD13-07 MULTIPARAMETRIC MRI OF THE BLADDER AS A PREDICTIVE FACTOR OF HISTOPATHOLOGY AT RETUR IN T1GH WITH PRESENCE OF DETRUSOR MUSCLE: COULD IT HAVE A ROLE? Andrea Giordano, Ettore Dalmasso, Eugenio Alessandria, Germano Chiapello, Diego Bernardi, Beatrice Carbonaro, Violino Paolo, and Ivano Morra Andrea GiordanoAndrea Giordano More articles by this author , Ettore DalmassoEttore Dalmasso More articles by this author , Eugenio AlessandriaEugenio Alessandria More articles by this author , Germano ChiapelloGermano Chiapello More articles by this author , Diego BernardiDiego Bernardi More articles by this author , Beatrice CarbonaroBeatrice Carbonaro More articles by this author , Violino PaoloViolino Paolo More articles by this author , and Ivano MorraIvano Morra More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003260.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The role of re-TUR in patients with T1 bladder tumor and muscle in TUR specimen remains controversial. Furthermore, re-TUR is an invasive procedure and a non-negligible source of logistic difficulties. On the other hand, the role of multi-parametric magnetic resonance imaging (mpMRI) for bladder cancer is growing, thanks to its high sensibility and specificity in the identification of local invasiveness of the tumor. We analyzed the role of MRI in the setting of repeated transurethral resection (reTUR) to predict absence of residual tumor (T0), persistence or understaging at first resection and we present our experience. METHODS: From April 2021 to September 2022 patients with diagnosis of T1HG bladder cancer and presence of detrusor muscle at first resection underwent a bladder MRI before reTUR, after 4 or 5 weeks from the first procedure. Ethical Committee approval has been obtained. Results were classified as no evidence of residual tumor, its evidence or understaging (according to VI-RADS score). MRI was 1.5 T. Accuracy was determined using histopathology as the reference standard. RESULTS: A total of 85 MRI was performed. 68 (80%) were classified as no residual tumor, 15 (17%) as residual tumor and 2 (3%) as suspected understaging at first resection. Accordancy with histopathology was 88%. Only in 10 (12%) cases MRI did not correctly predict results of reTUR: in 7 cases MRI classified as no residual tumors but histopathology found persistence of disease (of high grade), and 3 cases were classified as residual tumor but reTUR was negative. All 10 cases were intraoperatively macroscopically negative. The 2 cases of understaging were correctly predicted by MRI. Patients’ characteristics, tumor size, focality, site, prior recurrence rate, lymphovascular invasion, histological variants and hydronephrosis at staging CT-scan did not affect MRI accuracy. CONCLUSIONS: MRI is effective for prediction of histopathology at reTUR and could represent an effective tool in stratifying patients with T1HG who need second resection. Better instrumentation (3T-MRI), increasing experience and integration of modern prediction models can improve further our preliminary results, even including accurate cost analysis. Source of Funding: No © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e408 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Andrea Giordano More articles by this author Ettore Dalmasso More articles by this author Eugenio Alessandria More articles by this author Germano Chiapello More articles by this author Diego Bernardi More articles by this author Beatrice Carbonaro More articles by this author Violino Paolo More articles by this author Ivano Morra More articles by this author Expand All Advertisement PDF downloadLoading ...

Gastric Neuroendocrine Tumor Type 1: A Case Report

33-year-old patient who is referred to Endocrinology Outpatient Consultation in March 2021 due to the finding in gastric polyp biopsy 9 mm sessile located in greater curvature, of low-grade neuroendocrine tumor (ki-67 < 3%) without infiltration of the muscularis layer own. It is followed jointly with the Digestive Service, performing mucosectomy in April 2021 on carcinoid in major curvature of the stomach, where there is no evidence of residual tumor in the anatomo-pathological study (A-P). After completing the study with other complementary tests, gastric neuroendocrine tumor type 1 is diagnosed against the background of chronic atrophic gastritis. At present, the patient continues with periodic gastroscopic check-ups scheduled by the Digestive Service.

LBMON173 Non-functioning Seller Masses: Tumor Types, Surgical Management And Course Over Time

Abstract Introduction Pituitary adenomas (PA) are common. However, not all sellar tumors are PA. The specific diagnosis of a sellar mass can be difficult. Although there is abundant literature on PA, other types of sellar masses are not well described. In particular, their course over time and response to therapy are not well known. In this study, our objectives were to review non-functioning sellar masses treated with trans sphenoidal surgery (TSS) over the last 15 years to understand their types, success of surgery, and course over time. Patients and Methods We retrospectively reviewed all cases of non-functioning sellar masses managed at our hospital over the last 15 years (January 2007-December 2021). Out of 181 sellar masses that were resected by TSS during this period, 91 were functional PA and 90 were non-functional sellar masses. These sellar masses included non-functioning pituitary adenomas and other non-pituitary seller masses operated at our center during the above period and are the subject of this study. Results The patients included 29 (32%) females and 61 (68%) males with a median age of 41 years (range 13-75 years). The sellar masses were non-functional PA in 50 (55.6%)cases, atypical PA in 30 (33.3%) cases and non-PA in 10 (11%) cases. The 10 non-PA tumors included craniopharyngioma 3 cases, meningioma 3 cases, chordoma 1 case, giant cell tumor of the bone 1 case, spindle cell oncocytoma 1 case and Rathke cyst 1 case. The median largest tumor diameter was 3.15 cm (Interquartile range 2.2-4. 0). Only 5 cases (5.6%) were intrasellar, the other 85 cases (94.4%) had suprasellar (75 cases, 83%) and/or parasellar (32 cases, 35.6%) extension. Necrosis/cystic changes on MRI were present in 24 cases (26.7%). TSS was performed in 86 cases (95.6%) and transcranial surgery in 4 (4.4%) cases. The surgeries were complicated by transient central DI in 21 cases (23.3%), permanent CDI in 6 cases (6.7%), CSF leak in 8 cases (9%), bleeding in 2 (2.2%), stroke in 3 (3.3%) and partial or panhypopituitarism in 58 cases (64.4%). Twenty-two (24.4%) patients underwent a second TSS, 6 (6.7%) transcranial surgery, 32 (35.6%) external radiotherapy. At a median follow-up of 8.5 years (IQ range 4.63-12.18), only 19 (21%) patients had no evidence of residual tumor on follow-up MRI. The other 71 (79%) cases continued to have evidence of residual tumor, either completely intrasellar in 30 (33.3%) cases or with the suprasellar or parasellar residual component in 41 (45.6%) cases. Conclusions Non-functioning PA and other non-pituitary sellar tumors constitute 50% of sellar masses. Most are non-functioning PA, but atypical PA and other non-PA tumors can masquerade as PA. Most of these Non-functioning sellar masses are large with supra and parasellar extension. Surgery effectively reduces tumor size but is rarely curative and frequently complicated by hypopituitarism of variable severity and local complications. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Anaplastic Meningioma Who Grade III: Case Report and Review of Immunohistopathological Characteristics

Introduction: Anaplastic meningiomas constitute about 2% of all intracranial meningiomas and are known to be aggressive with a mean overall survival and mean relapse-free survival of 3.3 years and 2.7 years respectively. We treated a patient with a World Health Organization (WHO) grade III Anaplastic Meningioma, a rare histological variant of convexity meningiomas in which intraoperatively we found the tumor mass was unique of mixed characteristics particularly peritumoral subdural effusion Research Question: We show in this case report that convexity lesions presenting with subdural lesions should be highly suspected for WHO III anaplastic meningiomas backed with the immunohistopathological findings. Material and Methods: Routine computed tomography for patients with neurologic signs and symptoms which reveal a convexity peri-tumoral subdural collection should be suspected for WHO III anaplastic meningiomas. Surgery and adjuvant radiotherapy offered a good clinical outcome. Results: Postoperative the patient described a gradual improvement of the of expressive aphasia, deficits in speech, detectable personality changes or motor/sensory deficits. MRI at the three-month, six-month, one- year and two-year postoperative follow-up, revealed no evidence of residual tumor nor any observed recurrence nor recurrence of pre-operative symptoms. Discussion and Conclusion In this paper, we present the rare radiological presentation and immunohistopathological characteristics of this WHO III Grade III anaplastic meningioma. WHO III anaplastic meningiomas should be considered in the differential diagnosis of intracranial tumors which present with peritumoral subdural collection on routine contrast tomography imaging. Our findings may contribute to the literature of the histopathological nature and behavior of this tumor subtype.

Abstract 5572: T cell receptor modified with EDB-targeting ScFv and CD28 intracellular domain led to complete tumor regression in xenograft model

Abstract We explored use of chimeric antigen receptor T cell (CAR-T) for treatment of solid tumors, aiming at efficient killing of tumor cells while minimizing on-target off-tumor toxicities. We designed CAR targeting the extra domain B (EDB)-containing fibronectin, which is an oncofetal antigen widely expressed in tumor stroma and on the surface of cancer cells. Unlike membrane-spanning antigens, EDB-containing fibronectin is embedded in the extracellular matrix, and is enriched in new vasculatures and stromal tissues of tumor tissues. First, we made a second-generation EDB CAR (2G-EDB CAR) that killed EDB+ cells (U87MG, A549, and HUVEC) and showed tumor suppression in a U87MG xenograft tumor model. However, while in vitro the 2G-EDB CAR T cells were sufficiently cytotoxic, the in vivo inhibition of the tumor growth was moderate. Next we designed an EDB CAR that contained CD3ε to create 3ε-EDB CAR. We show that the 3ε-EDB CAR was incorporated into the T cell receptor (TCR) structure. The 3ε-EDB CAR completely displaced the native CD3ε in the TCR based on immune precipitation and Western analysis. The 3ε-EDB CAR was capable of inducing T cell activation and proliferation in the presence of EDB-fibronectin antigen. Further, the 3ε-EDB CAR T cells killed tumor cells containing EDB-fibronectin. In vivo, the 3ε-EDB CAR T cells demonstrated improved inhibition when compared to the 2G-EDB CAR T cells. To further enhance the EDB-targeting CAR, we added intracellular domain of CD28 to the 3ε-EDB CAR to create 3ε28-EDB CAR, and showed the 3ε28-EDB CAR was still incorporated into the TCR complex. The 3ε28-EDB CAR co-opted TCR complex and provided co-stimulatory signal upon binding of EDB antigens. Upon transduction of the 3ε28-EDB CAR into primary T cells, we observed upregulation of T cell activation markers CD25, CD69 and granzyme B in presence of the EDB antigen. We show that 3ε28-EDB CAR triggered the phosphorylation of CD3ζ, suggesting that EDB antigen stimulated co-opted TCR and signaled through the TCR-CD3 complex. T cells transduced with 3ε28-EDB CAR demonstrated stronger proliferation when activated by U87MG cells compared to 2G or 3ε-EDB CARs. Furthermore, 3ε28-EDB CAR T cells inhibited in vivo tumor growth in a dose-dependent manner, and most of the treated mice had no evidence of residual tumors. In conclusion, our results suggest that 3ε28-EDB CAR has great potential for treatment of solid tumors. Citation Format: Zhijie Zhang, Wen Qiu, Chang Liu, Muhan Wang, Yinghua Miao, Qingchao Ji, Rongchen Sun, Hongping Yin, Meijia Yang. T cell receptor modified with EDB-targeting ScFv and CD28 intracellular domain led to complete tumor regression in xenograft model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5572.

Circulating tumor DNA (ctDNA) in predicting residual disease after neoadjuvant chemoradiotherapy (nCRT) for esophageal squamous cell carcinoma (ESCC).

4044 Background: For ESCC patients who receive nCRT, high pathological complete response (pCR) rates could be achieved. An active surveillance strategy has been proposed for patients with clinically complete response (cCR) after nCRT. However, clinical assessment may misclassify non-pCR as cCR. This study aimed to investigate the value of ctDNA in predicting tumor response and residual disease after nCRT in ESCC patients. Methods: This was a side study of the prospective, diagnostic pre-SINO trial (NCT03937362). After completion of nCRT, all patients underwent one or two clinical response evaluations (CREs) before planned surgery. The first (CRE‐1) was 4–6 weeks after completion of nCRT. A second examination (CRE‐2) was 10–12 weeks after nCRT for patients without histological evidence of residual tumor at CRE1. Serial ctDNAs were analyzed by ultra-deep unique molecular identifiers -based next-generation sequencing using 168 cancer-related genes at three time points: at baseline (B0), CRE1, CRE2. pCR was defined as ypT0N0M0. cCR was defined as no evidence of residual tumor during CRE1 & CRE2 in endoscopic biopsies and endoscopic ultrasonography with fine-needle aspiration cytology. We correlated quantitative ctDNA levels and ctDNA presence with pCR and major locoregional residual disease (MLRD) ( > 10% residual carcinoma or any residual nodal disease). Results: At the time of this initial analysis, 62 consecutive ESCC patients received per-protocol treatments had sufficient sample to test ctDNA. The pCR rate was 32.3% (20/62). ctDNA was detectable in 73.77% at B0, 27.12% at CRE1 and 17.24% at CRE2. Maximum allelic fraction (maxAF) with a > 2-fold decrease post-nCRT (B0-CRE1) was seen in 67% patients with pCR, and 65.2% patients without MLRD. At B0, the high frequency mutated genes detected were TP53 (74%), PIK3CA (13%), CCND1 (11%), FGF19 (11%), FGF3 (11%), and FGF4 (11%). Baseline TP53 mutation status was significantly associated with pathological evaluations. A combining model, which incorporated both CRE1&2 positivity (cCR) and TP53 missense mutation at B0, was developed and demonstrated lower false-negative rate (FNR) in predicting non-pCR (4.9%, 2/41) and MLRD (2.8%, 1/36) compared with clinical assessment only (14.3%, 6/42) and (13.5%, 5/37), respectively. Of note, the FNR of combining clinical assessment and dynamic ctDNA change (continuous drop in maxAF ≥80% [B0-CRE1-CRE2]) was 7.3% (3/41) for non-pCR and MLRD (5.6%, 2/36). Conclusions: ctDNA testing combining with clinical assessment further optimized the tumor response and residual disease evaluations after nCRT for ESCC. ctDNA provides complementary information of response to nCRT and might become useful in an active surveillance strategy for the management of ESCC. Tumor-informed ctDNA analysis designed to track patient-specific somatic variants is ongoing. Clinical trial information: NCT03937362.

BRMP-03. Pituitary carcinoma: a case of dramatic response to immunotherapy (ipilimumab + nivolumab) after failure with temozolomide

Abstract INTRODUCTION Pituitary carcinoma (PC) accounts for just 0.1% of all pituitary tumors, often recurs following resection, and has a median reported survival of 1 year. Current treatment guidelines are not standardized but combine surgical resection, radiation therapy, and chemotherapy [1]. Temozolomide is the only chemotherapeutic with documented effectiveness, and the only recommended agent for aggressive pituitary carcinomas in ESE clinical guidelines [3]. CASE: A 57-year-old male presented with visual deterioration over a three-month period. Ophthalmologic evaluation revealed bitemporal visual field deficits. MRI brain W/WO demonstrated a sellar mass suspected to be pituitary macroadenoma with displacement of the stalk and optic nerve impingement (Figure 1a). The patient underwent stereotactic endoscopic transsphenoidal resection of the mass [2]. Postoperative MRI demonstrated gross total resection (Figure 1b). Pathology revealed a sparsely granulated corticotroph-adenoma with malignant transformation (early in-situ PC). Immunohistochemistry showed LOE of MLH1 and PMS2 in the tumor cells; Genetic analysis revealed MGMT methylation. Proton therapy was recommended given the elevated Ki67 index (75%) and p53 positivity. Before radiotherapy, there was no evidence of residual tumor or metastasis radiographically. He received 6600cGy of radiation over 33 fractions. Surveillance MRI showed recurrence at 21 months postoperatively, and temozolomide was initiated. However, MRI demonstrated marked progression after 3 cycles, and at 44 months, he developed a new 6th nerve palsy (Figure1c). Next-generation sequencing using the MSK-IMPACT platform identified somatic mutations in MLH1 Y548lfs*9 and TP53 R337C[4]. Immunotherapy with ipilimumab/nivolumab was initiated [5], and the patient noted resolution of his third nerve palsy soon after. MRI demonstrated a dramatic response with only minimal residual tumor burden (Figure1d). CONCLUSION PC is a rare tumor with frequent recurrence and a short median expected length of survival. Here we demonstrate the utility of immunotherapy in a single case report of PC. This treatment helped our patient survive well beyond the expected median life expectancy of this aggressive disease.

A scoping review on the "burned out" or "burnt out" testicular cancer: When a rare phenomenon deserves more attention.

The "burned out" or "burnt out" testicular cancer (BTC) indicates the spontaneous and complete regression of a testicular germ cell tumor in the presence of distant metastases at the diagnosis. As this condition was never reviewed systematically, a scoping review was conducted to scrutinize the available literature on clinical and histological features of BTC patients. Medline was searched from inception to 19 April 2020. A virtual cohort of 68 BTC patients was generated. Our findings highlighted some inconsistencies: BTC was diagnosed in 5,9% of patients not showing distant metastases and in 2,9% of patients who did not undergo an orchiectomy. Besides, evidence of residual tumor was found in 22,7% of testis specimens, recognized as seminoma in 40% of cases. The emerged inconsistencies may derive from the lack of an unequivocal definition of BTC. Larger collaborative studies are needed to define the best diagnostic workup and treatment for BTC patients.

RARE-10. PRIMARY INTRACRANIAL EWING SARCOMA IN A 12 MONTH OLD MALE

BackgroundEwing sarcoma (EWS) is a rare type of pediatric bone and soft tissue tumor that accounts for approximately 1% of all pediatric malignancies. It most commonly occurs in the long bones or axial skeleton, and rarely includes extraosseous sites or intracranial involvement. Reports of primary intracranial EWS are minimal. Pediatric intracranial EWS is even more rare with less than 15 cases reported. Case DescriptionWe describe the case of primary intracranial EWS in a 12 month old male. The patient’s initial MRI showed a large heterogeneous supratentorial cystic and solid mass centered in the right parietal region measuring 9.1cm x10.3cm x 7.6cm. No distant metastases were detected. The patient underwent surgical resection and pathology was consistent with a small round blue cell tumor. Further pathological evaluation revealed presence of EWSR1-FLI1 fusion and was negative for CD99, GFAP, synaptophysin, Olig2, desmin, and CAM5.2. Stains for INI1 and BRG1 were retained. The patient was treated with adjuvant chemotherapy and focal proton beam radiation (as per AEWS0031). ConclusionPrimary intracranial Ewing Sarcoma is a rare pediatric brain tumor and, to our knowledge, this would be the youngest reported case to date. This case demonstrates the successful application of a sarcoma-based regimen to a primary intracranial EWS tumor with no evidence of residual tumor on MRI at 8 months into treatment. Future studies should be directed at understanding the biology of these rare tumors and optimizing treatment approaches.

Abstract IA05: Innate immune defenses against cancer: Potential for mobilizing NK cells for cancer immunotherapy

Abstract Immunotherapies that mobilize CD8 T cells have revolutionized cancer therapy in recent years. A likely limitation of CD8 T cells in immunotherapy is that many tumors display few neoantigens and/or lack MHC I expression. Natural killer cells have emerged as exciting targets for new generations of immunotherapeutics. We investigated innate cues necessary for mobilizing spontaneous anti-tumor responses against tumors in mice and identified the cGAS-STING pathway as a critical pathway that is activated by cancer cells and mobilizes both NK cell and T cell mediated tumor rejection. Cyclic dinucleotides (CDNs) are STING agonists that, when injected into tumors, superactivate cellular immunity. We investigated the efficacy of CDNs in mobilizing anti-tumor activity in 6 independent gene edited models of MHC I-deficient tumors. Due to the absence of MHC I, CD8 T cells played no role in these responses. When transplanted syngeneic tumors of all 6 models were established and then treated intratumorally with CDNs (a single treatment, or in some cases 3 early treatments), tumor rejection rapidly ensued, which was NK-dependent and independent of CD8 T cells. In 5 of 6 MHC I-deficient tumor models tested, CDN therapy resulted in the indefinite survival of between 30% and 100% of the animals, with no evidence of residual tumors, suggesting the animals were cured. In one model (MHC I-deficient B16 melanoma cells) early rejection of the tumors was followed by relapse in all of the animals. Tumor rejection induced by CDNs was IFN-I-dependent, and conditional knockout experiments indicated that IFN-I acted directly on NK cells but also indirectly on DCs. After CDN therapy, DCs in the draining lymph nodes upregulated IL-15/IL-15R complexes on the membrane, and tumor rejection was blocked by neutralizing IL-15/IL15R. These data suggested that CDNs induce trans-presentation of IL15 by DCs to NK cells to support the tumor rejection response. CDN-induced tumor rejection was markedly enhanced by combining CDNs with IL-2 superkine (“super2”, in collaboration with C. Garcia), resulting in long-term tumor free survival in nearly all of the mice in the MHC I-deficient B16 and MC-38 models, indicating striking synergy between CDNs and super2. Our results suggest great potential for combining agonists of innate immune responses with superkines for treating cancers that are invisible to CD8 T cells, including MHC I-deficient cancers and potentially cancers with low neoantigen expression. Citation Format: David H. Raulet. Innate immune defenses against cancer: Potential for mobilizing NK cells for cancer immunotherapy [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr IA05.

Microsurgical Resection of an Intramedullary Spinal Cord Hemangioblastoma Through an Anterior Cervical Approach: 2-Dimensional Operative Video.

This video demonstrates the microsurgical removal of an intramedullary spinal cord hemangioblastoma through an anterior cervical approach. While most spinal hemangioblastomas arise from the dorsal or dorsolateral pial surface and can be safely resected through a posterior approach,1,2 ventral tumors can present a significant challenge to safe surgical removal.3-5 This patient presented with a progressively symptomatic ventral pial based hemangioblastoma at the C5-6 level with large polar cysts extending from C3 to T1. The tumor was approached through a standard anterior cervical exposure with a C5 and C6 corpectomy. Following midline durotomy, the tumor was identified and complete microsurgical resection was achieved. The principles and techniques of tumor resection are illustrated and described in the video. Following tumor resection and dural closure, a fibular allograft was inserted into the corpectomy defect and a C4-C7 fixation plate was placed. The patient was maintained in a supine position for 36 h. He was discharged home on postoperative day 3 in a cervical collar. The patient did well with near-complete recovery of neurological function. Postoperative magnetic resonance imaging at 6 wk showed a substantial resolution of the polar cysts and no evidence of residual tumor. The patient featured in this video consented to the procedure.

Transanal minimally invasive surgery for rectal neuroendocrine tumors.

There is no literature that mainly searched for rectal neuroendocrine tumor (rNET) using transanal minimal invasive surgery (TAMIS). We report our clinical experiences of TAMIS for rectal neuroendocrine tumors to evaluate the feasibility and safety. Between December 2010 and March 2020, the 25 consecutive patients with rectal neoplasma underwent the TAMIS procedure performed by single laparoscopic surgeon at the two hospitals. Of these, ten patients with rectal neuroendocrine tumors were reviewed retrospectively. The full-thickness excision down to the outer fatty tissues was completed using TAMIS technique. Clinicopathological findings, perioperative and postoperative complications were recorded. TAMIS for small rNET was successfully completed in all cases. There were seven cases with a tumor size of less than 10mm, and three cases with a tumor size between 10 and 15mm. Six patients underwent the primary tumor excision; the remaining four patients underwent resection for the scar after endoscopic procedure. The median surgical duration was 80.5 (53-124) minutes and the median blood loss was 1 (1-12) ml. All removed tumors in the 6 primary excisions were diagnosed as neuroendocrine tumor G1. The margins of specimens were completely free in all cases. Among the four patients after endoscopic procedure, all had no histological evidence of residual tumor. The median length of hospital stay was 7days postoperatively. There was no post-operative mortality or severe complication. The median length of observation was 54months. No recurrence, no local or distant metastasis and no mortality of all patients were observed. TAMIS is safety and feasible procedure for small rNET. Further experience and clinical trials are needed to fully define the advantages, disadvantages, and indications of TAMIS for rNET.

Accuracy of detecting residual disease after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma (preSINO trial): a prospective multicenter diagnostic cohort study

BackgroundAfter neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer, high pathologically complete response (pCR) rates are being achieved especially in patients with squamous cell carcinoma (SCC). An active surveillance strategy has been proposed for SCC patients with clinically complete response (cCR) after nCRT. To justify omitting surgical resection, patients with residual disease should be accurately identified. The aim of this study is to assess the accuracy of response evaluations after nCRT based on the preSANO trial, including positron emission tomography with computed tomography (PET-CT), endoscopy with bite-on-bite biopsies and endoscopic ultrasonography (EUS) with fine-needle aspiration (FNA) in patients with potentially curable esophageal SCC.MethodsOperable esophageal SCC patients who are planned to undergo nCRT according to the CROSS regimen and are planned to undergo surgery will be recruited from four Asian centers. Four to 6 weeks after completion of nCRT, patients will undergo a first clinical response evaluation (CRE-1) consisting of endoscopy with bite-on-bite biopsies. In patients without histological evidence of residual tumor (i.e. without positive biopsies), surgery will be postponed another 6 weeks. A second clinical response evaluation (CRE-2) will be performed 10–12 weeks after completion of nCRT, consisting of PET-CT, endoscopy with bite-on-bite biopsies and EUS with FNA. Immediately after CRE-2 all patients without evidence of distant metastases will undergo esophagectomy. Results of CRE-1 and CRE-2 as well as results of the three single diagnostic modalities will be correlated to pathological response in the resection specimen (gold standard) for calculation of sensitivity, specificity, negative predictive value and positive predictive value.DiscussionIf the current study shows that major locoregional residual disease (> 10% residual carcinoma or any residual nodal disease) can be accurately (i.e. with sensitivity of 80.5%) detected in patients with esophageal SCC, a prospective trial will be conducted comparing active surveillance with standard esophagectomy in patients with a clinically complete response after nCRT (SINO trial).Trial registrationThe preSINO trial has been registered at ClinicalTrials.gov as NCT03937362 (May 3, 2019).

How to differentiate spinal cord hemangiopericytoma from common spinal cord tumor?

IntroductionTumors of the spinal cord are rare and some can be confused with each other. We report a rare spinal cord solitary fibrous tumor/hemangiopericytoma (SFT/HPC), and propose keys to differentiate spinal cord tumors from each other. Case reportA 67-year-old man presented weakness with recent diffuse sensory disorders in the right lower limb. Spinal MRI revealed a T8-T9 intradural extramedullary mass with spinal cord compression. Gross total resection of a poorly vascularized intradural tumor was achieved. It was an encapsulated extramedullary tumor, which was difficult to separate from the spinal cord due to the presence of pial adhesions. Definitive diagnosis was grade 1 SFT/HPC of the spinal cord. One-year follow-up MRI revealed complete excision without any evidence of residual tumor. ConclusionSFT/HPC is a very rare spinal tumor that can be extramedullary, intramedullary or both. It may perfectly mimic meningioma. The maximal resection is the best treatment, but can be challenging because of the tumor's firm consistency and pial adherences to the spinal cord. Outcome is good in case of gross total resection, but there is a risk of very late recurrence, requiring long-term follow-up.

Follow-up of nutrition requirements of patients with head and neck cancer

Background: Head and neck cancer constitutes approximately 5.1% of all cancers worldwide. In these patients, nutritional problems present an immense and complex range of challenges. If the patient cannot swallow and the gastrointestinal tract is functioning normally, nutritional support is mainly given with enteral nutrition. The most common way to administer enteral feeding is via a polyurethane nasogastric feeding tube (NGT) or via a percutaneous endoscopic gastrostomy (PEG) tube. Objectives: Different cohorts of patients with Head & Neck cancer have been studied with the aim to identify patients requiring nutritional support and to improve the nutritional surveillance.Methods: In study I, the predictive value of systematic inflammatory and metabolic markers was prospectively studied in 21 patients undergoing RT. In Study II, a retrospective study of 151 patients with a PEG tube is presented. Study III Consecutive patients (n=147) with HEAD AND NECK cancer who were seen for nutritional control were evaluated for factors contributing to body weight loss. Study IV Using a prospective design, interviews about what in life is influenced by disease and feeding (oral feeding, NGT or PEG) were conducted. Results: In Study I, all patients lost body weight with the greatest loss at the end of RT. Highly sensitive C-reactive protein (hsCRP) increased during RT. In study II, complications were seen in 40% of the patients. In study III, lowest body weight was observed at 6 months after RT. In total, 82 patients with no evidence of residual tumour after treatment received enteral nutrition. Body weight loss was not found to be associated with post-operative infections or mortality. In Study IV, more than 45% of the patients manifested eating-related problems. Conclusion: Body weight and CRP are valuable variables to follow-up. NGT should be regarded as the first choice of enteral nutrition in patients with an expected limited time of tube feeding, whereas in patients in which prolonged treatment is needed PEG can be the choice. The extended body weight loss after treatment indicates that a pre-treatment nutritional surveillance programme is important.