Recurrent Tumor Growth Research Articles

OTHR-01. Papillary tumor of pineal region rare pediatric CNS tumor: case series treated in King Fahad Medical City KFMC

Abstract Clinical behaviors, prognosis, and appropriate treatments of PTPR are not fully defined due to the rarity of these tumors. At diagnosis, PTPR may present with various clinical symptoms with obstructive hydrocephalus, as well as neurological signs including Parinaud’s syndrome. Radiological assessment of pineal region lesions is challenging with a wide range of potential differential diagnoses. PTPR typically presents as a heterogeneous, well circumscribed mass in the pineal region. we report 3 female pediatric cases of PTPR treated in our institution. Histological and immunohistochemical diagnosis was confirmed by analysis of genome-wide DNA methylation profiles. the first case presenting with spinal leptomeningeal dissemination with excellent tumor control with radiation therapy alone. The second patient had aggressive course with recurrent local tumor growth despite radiation therapy and 0repeated surgical resections and she responded well to Pineoblastoma like intensive chemotherapy6 repeats of alternating 4-week cycles A&B : Cycle A: Cisplatin 90 mg/m2/day, day 1 of a & oral Etoposide 35 mg/m2/day P.O. days 1-21 . Cycle B: Cyclophosphamide 1 g/m2/day, days 1 and 2, Vincristine 1.5 mg/m2, days 1, 8 . While the third patient after first near gross total surgical resection with no recurrence for 18 months without adjuvant therapy then she had local recurrence which was salvaged by second complete resection and focal radiation The proper therapeutic strategy for PTPR is not clearer and the clinical behavior of PTPRs can be compared to that of ependymoma with complete resection is the mainstay of treatment and we recommend that adjuvant therapies like radiation with or without or chemotherapy should be considered when complete surgical resection is not feasible. This case series expands on the available reports on the clinical presentations of PTPR and provides important information on the responses to different treatments modalities

Aggressive giant prolactinoma: a case report

BackgroundManaging treatment-resistant aggressive giant prolactinoma can be challenging, as the diagnosis is often complex, and treatment beyond dopamine agonists, surgery, and radiotherapy is limited.Case presentationA 21-year-old Malay woman first presented to our hospital at the age of 16 years with 1-year history of reduced vision and 2 years of amenorrhea. Her baseline prolactin level was 255,894 µIU/mL with secondary hypogonadism, and pituitary magnetic resonance imaging revealed a giant prolactinoma (2.8 × 3.2 × 4.2 cm3) with suprasellar extension and optic chiasmal compression. She was initially treated with cabergoline, and reductions in the prolactin level and tumor mass were achieved, leading to vision improvement and resumption of normal menstruation. However, she developed recurrent tumor growth and hyperprolactinemia, causing relapse of symptoms, and she needed surgery. Eventually, despite three tumor debulking surgeries and escalation of cabergoline doses up to 1 mg/day, her tumor progressed with aggressive characteristics. Following a multidisciplinary meeting, the patient is initiated on temozolomide therapy after considering the long-term side effects of radiotherapy in her case.ConclusionThis case highlights the importance of early identification of treatment-resistant prolactinoma and the need for a multidisciplinary approach in managing aggressive prolactinoma in young patients, particularly regarding timely implementation of temozolomide therapy.

Результаты хирургического лечения пациентов с нейрогенными опухолями лицевого нерва интратемпоральной локализации

Objectives. To describe surgical outcomes of neurogenic facial nerve tumors (NFNT). Patients and methods. The study included 18 patients with intratemporal NFNT, 12 women and 6 men. The average age was 41,4 ± 18,9 years (range from 3 to 66 years). To assess the facial nerve (FN) function, a 6-step House–Brackmann scale was used. Tumors were removed mainly by the transmastoid route. The translabyrinthine approach was performed in the case of a labyrinth segment of the FN involved. Two patients underwent a combined transmastoid-middle fossa approach in the case of tumor spreading into the middle cranial fossa. Facial nerve reconstruction performed by end-to-end neurorrhaphy or with the sural nerve autograft in the case of a nerve deficiency. Recurrence or continued tumor growth was monitored by contrast-enhanced MRI at the last visit. Results. The most common tumor lesions were the mastoidal (66,7%) and tympanic (55,6%) segments of the FN. Multiple-segment involvement was in 10 cases (55,6%). All patients were admitted for surgical treatment with signs of paresis of mimic muscles of II–VI degree. Improvement of the FN function was achieved in 10 patients (55,6%), in 5 cases with n.suralis autograft. In 6 cases (33,3%), the FN function remained to the preoperative level, in 3 of them, with the use of an autograft. The FN function downgraded in 2 cases (11,1%) without FN reconstruction. Recurrence or continued growth of the residual tumor was detected in 2 patients (11,1%). Hearing improvement was achieved in 12 cases (66,7%), hearing decrease was obtained in 2 cases (11,1%), in 4 cases hearing remained at the preoperative level (22,2%). Conclusion. Surgical approach should be adequate to the spread of the tumor process and consider the possibility of hearing preservation. When the geniculate node and the labyrinth segment of the FN are involved, it is advisable to use access through the middle cranial fossa with socially adequate hearing. Timely and adequate surgical treatment allows maintaining or improving the function of the facial nerve in most cases (88,9%).

CD47-targeted optical molecular imaging and near-infrared photoimmunotherapy in the detection and treatment of bladder cancer

Transurethral resection of bladder tumor (TURBT) followed by intravesical therapy remains the most effective strategy for the management of non-muscle-invasive bladder cancer worldwide. TURBT has two purposes: to remove all visible tumors and to obtain tumor specimens for histopathological analysis. However, the detection of flat and small malignant lesions under white-light cystoscopy is extremely challenging, and residual lesions are still the main reason for the high recurrence rate of bladder cancer. We hypothesized that visual enhancement of malignant lesions using targeted optical molecular imaging could potentially highlight residual tumors in the bladder during surgery, and near-infrared photoimmunotherapy (NIR-PIT) could kill exfoliated cancer cells and residual tumors. A mouse model of complete or partial bladder tumor resection was established under the guidance of optical molecular imaging mediated by indocyanine green and anti-CD47-Alexa Fluor 790, respectively. Once the tumor recurred, mouse model received repeated CD47-targeted NIR-PIT. After complete resection, there was no tumor recurrence. Furthermore, the growth rate of recurrent tumor decreased significantly after repeated NIR-PIT. Therefore, CD47-targeted optical molecular imaging can potentially assist urologists to detect and remove all tumors, and repeated NIR-PIT shows the potential to reduce tumor recurrence rates and inhibit the growth of recurrent tumor.

In situ gel implant for postsurgical wound management and extended chemoimmunotherapy against breast cancer recurrence

Postsurgical recurrence of breast cancer is closely related to the inflammatory tumor microenvironment evoked by surgical wounds. Toll-like receptor 4 (TLR4) signaling contributes to NF-κB activation thus secreting various inflammatory cytokines. Herein, we developed an in situ photo-crosslinked hydrogel (D/T gel) concurrently loaded with doxorubicin (DOX) and a TLR4 antagonist, resatorvid (TAK-242). Its therapeutic effect against breast cancer postsurgical relapse was accomplished through remodeling the proinflammatory tumor microenvironment. The obtained gel network exhibited ideal biodegradability and biocompatibility, which motivated dermal wound healing in the full thickness wound model in mice. Despite the initial burst release of DOX, D/T gels exhibited extended-release of both DOX and TAK-242 for up to 21 days in vitro. TAK-242 was demonstrated to inhibit the lipopolysaccharide-induced NF-κB activation and downregulate TLR4 levels in both RAW264.7 and 4T1 cells. In a 4T1-Luc tumor postsurgical recurrence model, D/T gel significantly suppressed recurrent tumor growth by elevating the concentrations of DOX and TAK-242 at the tumor sites and remodeling the TLR4 activation-induced proinflammatory microenvironment. Overall, the D/T gel platform technology is proven to deliver therapeutics directly to the surgical wound bed, attenuating the dual inflammatory responses induced by DOX and surgical wounding thus greatly potentiating its efficacy in preventing postsurgical tumor recurrence. Statement of significancePostsurgical recurrence of breast cancer is closely related to the inflammatory tumor microenvironment (TME) evoked by surgical wounds. Although chemotherapeutics lead to extensive residual tumor cell necrosis, multiple inflammatory cytokines are secreted simultaneously, which are conducive to tumor recurrence. In this work, a TLR4 antagonist, TAK-242, was combined with DOX to reverse the dual inflammatory TME induced by surgical wounding and chemotherapy. To elevate the concentration of therapeutics at the tumor site, a photocrosslinked hydrogel (D/T gel) implant coloaded with TAK-242 and DOX was developed and applied on the postsurgical bed. Consequently, D/T gel attenuated the dual inflammatory responses and greatly potentiated its efficacy in preventing postsurgical tumor recurrence.

Single Arm Prospective Trial on BOLD fMRI Radiation-Induced Changes in Newly Diagnosed Glioblastoma Patients

<h3>Purpose/Objective(s)</h3> Standard therapy for patients with glioblastoma (GBM) consists of maximal safe surgical resection followed by concurrent chemotherapy and radiation (CRT) to the postoperative cavity and residual disease. After CRT, patients are standardly assessed at regular intervals of approximately 1-4 months with magnetic resonance imaging (MRI) of the brain to monitor for residual or recurrent tumor growth. At present, there are no accepted MRI methods or protocols to predict response either during or after CRT. Notably, GBM is associated with vascular dysregulation, manifesting radiographically as asynchrony on resting state BOLD fMRI. However, the impact of radiation therapy on BOLD asynchrony in glioblastoma remains unknown. In this study, we sought to collect radiographic data on a cohort of patients with recently resected glioblastoma prior to the start of CRT and again during the third week of therapy. The aim of this prospective pilot study was to determine the feasibility of collecting radiographic data to inform patient outcomes and ultimately predict the interval to disease progression of GBM using pre-treatment and mid-treatment MRI acquisitions. <h3>Materials/Methods</h3> Twelve patients with newly-diagnosed histologically proven GBM were enrolled in this institutional IRB approved prospective trial between 2015 and 2017. Patients underwent two resting-state BOLD fMRI scans: one immediately prior to starting standard six weeks of radiation and another during the third week of radiation. BOLD scans were processed and linearly registered to structural images. A BOLD asynchrony map was generated by comparing the time series in each voxel to the time series of the contralesional, radiographically normal brain, such that positive values denote synchrony with the contralateral hemisphere. The 60 Gy radiation dose maps were used for the purposes of determining the total radiation dose at each voxel. <h3>Results</h3> There were 8 males and 4 females included in the analysis with a median age at diagnosis of 63 years. We divided the brain into voxels that received lower total doses of radiation (< 24 Gy) and higher total doses of radiation (> 24 Gy), and determined the mean change in the BOLD asynchrony before and during radiation for each group of voxels for each patient. The absolute change in BOLD asynchrony between the two scanning sessions was significantly higher in the regions that received higher doses of radiation (0.71 vs 0.04, <i>P</i> = 0.0007). <h3>Conclusion</h3> Here we show that radiation doses higher than 24 Gy change vascular regulation in glioblastoma patients, manifesting as altered asynchrony on resting-state BOLD fMRI. Further prospective evaluation is warranted to develop a non-invasive radiographic biomarker to predict and monitor responses to standard interventions for glioblastoma.

S1826 Case Series: Successful Endoscopic Resection of Colorectal Leiomyomas

Introduction: Colorectal leiomyomas are relatively uncommon, accounting for 3% of all gastrointestinal leiomyomas. Leiomyomas are often identified incidentally; however, some patients may present with symptoms of abdominal pain or rectal bleeding. Surgical resection was historically the standard of care for removal of these smooth muscle tumors, particularly for tumors larger than 2 cm. However, with ongoing advances in endoscopic techniques, endoscopic polypectomies have fallen into favor for management of these submucosal lesions as it is less invasive and less costly. We present two cases of colorectal leiomyomas that were successfully managed endoscopically without surgical intervention. Case Description/Methods: A 69-year-old male presented to the gastroenterology clinic for colorectal cancer screening. He endorsed 3 to 4 bouts of watery diarrhea daily and 15-pound unintentional weight loss over one year duration. A colonoscopy was subsequently performed revealing a 1cm pedunculated polyp in the descending colon [See Figure 1]. The base of the polyp was injected with 4mL of 1:100,000 epinephrine with adequate lift. A hot snare polypectomy was performed using standard ERBE settings. Pathology revealed a submucosal benign mesenchymal neoplasm. Immunohistochemical staining was strongly positive for Smooth Muscle Actin (SMA) and Desmin, solidifying the diagnosis of leiomyoma. A 41-year-old male was seen by the gastroenterology division on the inpatient service for evaluation of rectal bleeding. A colonoscopy was performed revealing a 4mm sessile polyp in the rectum that was completely removed via cold biopsy forceps [See Figure 2]. Pathology revealed a microscopic submucosal spindle cell lesion. Immunohistochemical staining was positive for SMA with no expression of CD-117 and DOG-1, supporting the diagnosis of leiomyoma. Discussion: The optimal therapeutic approach for large colorectal leiomyomas remains controversial but usually depends on the location, size, and direction of tumor growth. Our patients were managed successfully with endoscopic resection alone. Both patients had a surveillance colonoscopy that revealed no residual tumor or recurrence of tumor growth. These benign smooth muscle tumors have excellent prognosis and typically do not recur after removal. These cases support the notion that leiomyomas can often be removed endoscopically with limited morbidity and have excellent outcomes.Figure 1.: 1 cm pedunculated polyp in descending colon (case 1).Figure 2.: 4 mm sessile polyp in rectum (case 2).

Фактори ризику рецидиву неактивних аденом гіпофіза у хворих із дефіцитом гормона росту

Актуальність. На даний час залишається актуальним пошук діагностично значущих маркерів агресивності неактивних аденом гіпофіза (НАГ) для визначення подальшого прогнозу в постопераційному періоді. Аденоми гіпофіза, що не мають клінічних проявів гіперсекреції гіпофізарних гормонів, є формами доброякісних пухлин аденогіпофіза. У загальній популяції частота НАГ становить 50 випадків на 1 млн населення. Мета дослідження: визначити клініко­діагностичні маркери агресивності пухлини у хворих із НАГ і дефіцитом гормона росту і їх роль у формуванні тяжкості нейроендокринної симптоматики захворювання. Матеріали та методи. Під наглядом перебувало 87 хворих (із них чоловіків — 44, жінок — 43) із верифікованим діагнозом НАГ після трансназальної гіпофізектомії; період спостереження — від одного до трьох років. Результати. При розподілі хворих на групи залежно від гістологічної характеристики НАГ переважали пацієнти з крупноклітинною хромофобною аденомою гіпофіза (77,5 %). НАГ у жінок супроводжувалася ожирінням, первинним і вторинним гіпотиреозом, вторинним гіпогонадизмом, синдромом персистуючої галактореї — аменореї (симптоматична й ідіопатична форми), нецукровим діабетом, синдромом порожнього турецького сідла та ін. У чоловіків НАГ супроводжувалася ожирінням, первинним і вторинним гіпотиреозом, вторинним гіпогонадизмом, нецукровим діабетом, гінекомастією. Розроблена шкала маркерів агресивності НАГ дозволила ідентифікувати фактори за трьома ступенями і розробити комплекс профілактичних заходів, покликаних унеможливлювати рецидив зростання пухлини. Висновки. Маркерами агресивності перебігу НАГ є: молодий вік пацієнта, перші симптоми маніфестації хвороби, великі розміри пухлини, асиметричність і деформація гіпофіза, ознаки інвазії пухлини в сусідні тканини/артерії/кавернозний синус, наявність дрібноклітинних і/або темноклітинних хромофобних аденом, пангіпопітуїтаризм.

In situ Gel Implant for Postsurgical Wound Management and Extended-Chemoimmunotherapy Against Breast Cancer Recurrence

Postsurgical recurrence of breast cancer is closely related to the inflammatory tumor microenvironment evoked by surgical wounds. Toll-like receptor 4 (TLR4) signaling contributes to NF-κB activation thus secreting various inflammatory cytokines. Herein, we developed an in situ photo-crosslinked hydrogel (D/T gel) concurrently loaded with doxorubicin (DOX) and a TLR4 antagonist, resatorvid (TAK-242). Its therapeutic effect against breast cancer postsurgical relapse was accomplished through remodeling the proinflammatory tumor microenvironment. The obtained gel network exhibited excellent biodegradability and biocompatibility, which motivated dermal wound healing in the full thickness wound model in mice. Despite the initial burst release of DOX, D/T gels exhibited extended-release of both DOX and TAK-242 for up to 21 days in vitro . TAK-242 was demonstrated to inhibit the lipopolysaccharide-induced NF- κ B activation and downregulate TLR4 levels in both RAW264.7 and 4T1 cells. In a 4T1-Luc tumor postsurgical recurrence model, D/T gel significantly suppressed recurrent tumor growth by elevating the concentrations of DOX and TAK-242 at the tumor sites and remodeling the TLR4 activation-induced proinflammatory microenvironment. Overall, the D/T gel platform technology is proven to deliver therapeutics directly to the surgical wound bed, attenuating the dual inflammatory responses induced by DOX and surgical wounding thus greatly potentiating its efficacy in preventing postsurgical tumor recurrence.

Recurrent desmoid-type retroperitoneal fibromatosis: clinical observation

This article deals with the rare clinical observation of the patient with recurrent desmoid-type fibromatosis, who have achieved long-term stability after surgical treatment. A 24-year-old patient was diagnosed with retroperitoneal tumor which size was 8.85.613 cm in 2013, infiltrating the left psoas muscle, left kidney, left common and left external iliac arteries, descending colon and sigmoid colon. The patient underwent surgery in the volume of the tumor removal, resection of the left common iliac artery and prosthetics using GORE-TEX prosthesis, left hemicolectomy, left nephrectomy at Blokhin National Medical Research Center of Oncology. The first recurrence of the tumor was detected nine months after the surgery. Due to the subsequent growth of tumor mass, located along the left external iliac artery and in the inguinal canal, the repeated surgery was performed. Then the patient had a second relapse, and underwent surgery again. The third recurrence was detected seven months after the last surgery. During the multidisciplinary discussion, according to the absence of complaints and the small size of the recurrent tumor, as well as the absence of the risk of life-threatening complications, it was decided to stop on the observation. The patient was examined once every six months there were no data concerning recurrent tumor growth. Today, the patient is alive, does not have any complaints and is able-bodied. Our clinical observation demonstrates that active surgical tactics in case of the retroperitoneal fibromatosis recurrence not always can lead to long-term progression-free survival time and several patients can stay under the observation, using Look and Stay tactic.

G9a Promotes Breast Cancer Recurrence through Repression of a Pro-inflammatory Program

SUMMARYDysregulated gene expression is a common feature of cancer and may underlie some aspects of tumor progression, including tumor relapse. Here, we show that recurrent mammary tumors exhibit global changes in gene expression and histone modifications and acquire dependence on the G9a histone methyltransferase. Genetic ablation of G9a delays tumor recurrence, and pharmacologic inhibition of G9a slows the growth of recurrent tumors. Mechanistically, G9a activity is required to silence pro-inflammatory cytokines, including tumor necrosis factor (TNF), through H3K9 methylation at gene promoters. G9a inhibition induces re-expression of these cytokines, leading to p53 activation and necroptosis. Recurrent tumors upregulate receptor interacting protein kinase-3 (RIPK3) expression and are dependent upon RIPK3 activity. High RIPK3 expression renders recurrent tumors sensitive to necroptosis following G9a inhibition. These findings demonstrate that G9a-mediated silencing of pro-necroptotic proteins is a critical step in tumor recurrence and suggest that G9a is a targetable dependency in recurrent breast cancer.

Abstract 6247: Drug delivery with real time customizable micro-scaled continuous liquid interface printed 3D devices

Abstract Background: Surgery is a key treatment for cancer. However, local recurrence after surgery is common and can lead to significant morbidity and mortality. Current strategies to prevent recurrence include intraoperative radiation or systemic chemotherapy. We hypothesize that local chemotherapy delivery can prevent recurrence while reducing toxicity. To accomplish this, we propose to engineer 3D printed devices that can deliver chemotherapy in a localized and prolonged fashion. Methods: Paclitaxel and a cisplatin prodrug were dissolved into a liquid resin mixture of PEG550-DMA and HEMA. Custom 3D patches were printed on a Carbon 3D continuous liquid interface printer with microneedles protruding from one side of a flat surface substrate. A non-drug loaded flat backing was also printed from the same resin, and adhered to back side of the microneedle patch. Tumor growth recurrence inhibition post surgical resection was assessed in NU/NU mice in both 344SQ/Luc and A431 tumor models. Tumors were inoculated subcutaneously (106 344SQ/Luc, 5 × 105 A431) and allowed to grow until they reached 5-7mm in length. Tumors were then surgically resected and mice were either given an IV drug treatment, or had a 3D printed patch implanted in the surgical pocket. Tumor recurrence was evaluated with both luciferase bioluminescence imaging and physical measurement of tumor size. Toxicity parameters were analyzed with enzyme and CBC tests. Results: All drug loaded patches showed significant tumor growth inhibition compared to their corresponding IV drug treatment groups. While single drug loaded patches were significant in their inhibition of tumor growth compared to IV delivery of the same drug, dual drug loaded patches showed the most significant tumor inhibition compared to either single IV drug treatment or a dual IV drug treatment. There were no significant differences in measured toxicity parameters between groups. Conclusions: Our data demonstrated that local drug delivery through a customizable 3D continuous liquid interface printed drug loaded patch can improve tumor growth recurrence inhibition post surgical resection. Citation Format: C. Tilden Hagan, Cameron J. Bloomquist, Joseph M. DeSimone, Andrew Z. Wang. Drug delivery with real time customizable micro-scaled continuous liquid interface printed 3D devices [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6247.

Absence of impact of direct acting antivirals for hepatitis C virus on recurrent hepatocellular carcinoma tumor growth in the AFEF/ANRS CO22 Hepather cohort

Although it has now been excluded that direct-acting antivirals (DAA) are associated with a significant risk of hepatocellular carcinoma (HCC) in HCV-infected patients, a possible effect of DAA on tumor growth is still a subject of debate. We performed a blind comparison of the kinetics of HCC recurrence in patients after HCV treatment with or without DAA to evaluate the potential aggressiveness of HCC after DAA treatment. Thirty-nine HCV-infected patients from the AFEF/ANRS CO22 Hepather cohort who experienced HCC recurrence after so-called curative treatment were evaluated. Contrast-enhanced CT and/or MR images were read blindly 6 months before HCC recurrence and during the follow-up period. Seventeen patients who received DAA (DAA+) before HCC recurrence were compared to the 22who did not receive (DAA-), according to the LiRads and mRECIST criteria. There were 28 men and 11women, median age 62 years old, 37 (95%) with cirrhosis. DAA+ patients had a lower median MELD score (8±2 vs. 10±4, P=0.0286) than DAA- patients. The median time to HCC recurrence (time from the date of curative treatment to the diagnosis of recurrence) was not different (20 vs. 18 months) (P=0.73) between the two groups. There was no difference between the 2 groups in the overall survival and/or transplantation-free survival (P=0.71) and for the mRECIST time to progression (P=0.25). This blinded analysis of HCC recurrence after HCC treatment does not support any negative impact of DAA therapy on the severity or progression of recurrent HCC.

Nimotuzumab, an EGFR‑targeted antibody, promotes radiosensitivity of recurrent esophageal squamous cell carcinoma.

Local tumor recurrence is one of the main causes for the failure of esophageal cancer treatment following radiotherapy. Previous studies have demonstrated that epidermal growth factor receptor(EGFR)‑targeted therapy combined with radiotherapy is expected to become an effective means to control tumor recurrence. The aim of the present study was to investigate the effect and mechanism of nimotuzumab (an EGFR‑targeted antibody) in the treatment of recurrent esophageal carcinoma. The radiation responses of two esophageal squamous carcinoma cell lines, EC109 and TE‑1, with or without nimotuzumab, were first evaluated by CCK‑8 assay. Colony formation and apoptosis were used to measure anti‑proliferation effects. It was demonstrated that nimotuzumab arrested the cell cycle at the G2phase invitro. Western blotting and immunofluorescence analysis were used to determine signaling pathway changes. It was observed that nimotuzumab inhibited phosphorylation of EGFR in EC109 cells. Furthermore, recurrent tumor models were established and it was identified that the degree of tumor hypoxia was positively associated with EGFR overexpression. In EC109 cell xenografts, nimotuzumab combined with radiation led to a significant delay in recurrent tumor growth compared with that of radiation alone (P<0.001 for 0Gy pre‑irradiation, P=0.005 for 20Gy pre‑irradiation, P=0.005 for 10Gy pre‑irradiation). These results suggest that nimotuzumab combined with radiation may be an effective means to control recurrent esophageal squamous cell carcinoma with EGFR overexpression.

Inferior turbinate neoplasms

The main aim of the work was to describe a rare clinical case of osteoma of inferior turbinate. The interest of the case is that such tumors are extremely rare. A female patient of 63 years old attended an ENT clinic. She complained on absence of nasal breath at the right side and headache. After a full ENT-examination, anamnesis, and a thorough analysis of the radiation examination results (computed tomography data), a decision was made to surgical treatment. Under general anesthesia, controlled hypotension surgery was done. First step was septoplasty, then the dense bone tumor was reduced and removed. At the control examination in 3 months, the complete removal of the formation of the inferior turbinate on the right is determined. There were no signs of continued or recurrent tumor growth. Neoplasms of the nasal cavity, in particular the inferior turbinate, are extremely rare pathologies. They are mainly detected when performing anterior rhinoscopy, endoscopic examination of the nasal cavity. The result of histological examination is compact osteoma. The gigantic size of the inferior turbinate osteoma in our case is probably due to the patient's failure to consult a specialist (otorhinolaryngologist) for a long time. Surgical treatment of this pathology should consist in an endoscopic endonasal approach: this approach allows the most complete and minimally traumatic removal of the tumor.

Integration of PET-imaging into radiotherapy treatment planning for low-grade meningiomas improves outcome.

Meningiomas have an excellent survival prognosis, and radiotherapy (RT) is a central component of interdisciplinary treatment. During treatment planning, the definition of the target volume remains challenging using MR and CT imaging alone. This is the first study to analyze the impact of additional PET-imaging on local control (LC) and overall survival (OS) after high-precision RT. We analyzed 339 meningiomas treated between 2000 and 2018. For analyses, we divided the patients in low-grade (n = 276) and high-grade (n = 63) cases. We performed RT in an adjuvant setting due to subtotal resection or later due to recurrent tumor growth. The target volumes were delineated based on diagnostic CT and MRI and, if available, additional PET-imaging (low-grade: n = 164, 59.4%; high-grade: n = 39, 61.9%) with either 68Ga-Dotanoc/Dotatoc, 18F-fluoroethyltyrosine or 11C-methionine tracer. Patients were treated with fractionated stereotactic RT with a median total dose and dose per fraction of 54 Gy and 1.8 Gy, respectively. Median follow-up was 5.6 years. For low-grade meningiomas, mean OS was 15.6 years and mean LC was 16.9 years; for high-grade cases mean OS was 11.6 years, and mean LC was 11.1 years. In univariate analyses, PET-imaging had a significant impact on OS (p = 0.035) and LC (p = 0.041) for low-grade meningiomas and remained significant (p = 0.015) for LC in the multivariate analysis. For high-grade cases, PET did not influence both OS and LC. Further prognostic factors could be identified. For low-grade meningiomas, we showed that the addition of PET-imaging for target volume definition led to a significantly enhanced LC. Thus, PET improves the detection of tumor cells and helps distinguish between healthy tissue and meningioma tissue, especially during the treatment planning process.

(-)-Oleocanthal Prevents Breast Cancer Locoregional Recurrence After Primary Tumor Surgical Excision and Neoadjuvant Targeted Therapy in Orthotopic Nude Mouse Models.

Breast cancer (BC) recurrence represents a challenge for survivors who have had their primary tumors surgically excised, and/or have completed radiation, neoadjuvant, or adjuvant therapeutic regimens. Current BC treatments mostly lack the ability to reduce the risk of disease recurrence. About 70% of BC patients will subsequently suffer disease relapse, manifesting as local, regional, or distant tumor recurrence, which clearly underscores the urgent need to discover novel recurrence inhibitors. (−)-Oleocanthal (OC) is a natural phenolic, found so far exclusively in extra-virgin olive oil (EVOO). OC exerts documented bioactivities against diverse cancer types, inflammation, and neurodegenerative diseases. Herein we report the novel activity of daily oral treatment with OC (10 mg/kg) in preventing BC locoregional recurrence in a nude mouse xenograft model generated by orthotopic inoculation with BT-474 cells as a luminal type B model. We further report inhibition of tumor recurrence by OC after completion of a lapatinib neoadjuvant regimen. However, in a recurrence model of triple-negative breast cancer (TNBC), OC treatment (10 mg/kg) did not effectively prevent tumor recurrence, but rather, was seen to significantly reduce the growth of recurrent tumors as compared to vehicle control-treated animals. Inhibition of tumor recurrence was associated with significant serum level reductions of the human BC recurrence marker CA 15-3 at the study end in animals treated with OC. OC treatment upregulated the expression of the epithelial marker E-cadherin and downregulated the levels of the mesenchymal marker vimentin in recurrent tumors vs. untreated control animals. OC treatment also reduced the activation of MET and HER2 receptors, as indicated by reduced phosphorylation levels of these proteins in recurrent tumors vs. controls. Collectively, the results of our studies provide the first evidence for suppression of BC tumor recurrence by oral OC treatment in an animal model for such recurrence, and furthermore, highlight favorable prospects for this natural product to emerge as a first-in-class BC recurrence inhibitor.

SAT-490-No impact of direct-acting antivirals on recurrent hepatocellular carcinoma tumour growth in the ANRS CO22 Hepather Cohort

SAT-490-No impact of direct-acting antivirals on recurrent hepatocellular carcinoma tumour growth in the ANRS CO22 Hepather Cohort

Paclitaxel-Induced Src Activation Is Inhibited by Dasatinib Treatment, Independently of Cancer Stem Cell Properties, in a Mouse Model of Ovarian Cancer.

Approximately seventy percent of ovarian cancer patients succumb to the disease within the first 5 years of diagnosis, even after successful surgery and effective chemotherapy treatment. A small subset of chemotherapy resistant cancer stem cells (CSCs) cause relapse of ovarian cancers. This study investigated the association between paclitaxel-mediated Src activation (p-Src) and CSC populations in driving ovarian cancer progression. We demonstrate that patients with high-stage serous ovarian carcinomas have significantly elevated levels of p-Src, compared to patient with low-stage and benign ovarian tumours. Additionally, p-Src was significantly enhanced in ascites-derived tumour cells obtained from recurrent patients, compared to chemonaïve patients. Paclitaxel treatment increased Src activation in ovarian cancer cells, causing enrichment of CSC marker expression in the surviving cells in vitro and in xenografts of nude mice. Dasatinib in combination with paclitaxel significantly suppressed p-Src in ovarian cancer cell lines and xenografts but had no effect on the expression of CSC markers. However, combination of paclitaxel and Dasatinib showed lower trend in invasion in liver and pancreas, compared to paclitaxel-only treatment. The tumours treated with combination therapy also had significantly lower infiltration of mononuclear cells. Robust recurrent tumour growth was observed in all mice groups after termination of treatments. The above results suggest that Dasatinib-mediated inhibition of p-Src may not be crucial for paclitaxel-induced CSC-mediated recurrence in ovarian cancer.

Optimizing poly (ADP-ribose) polymerase inhibition through combined epigenetic and immunotherapy.

Triple‐negative breast cancer (TNBC) is an aggressive breast cancer subtype with poor survival outcomes. Currently, there are no targeted therapies available for TNBCs despite remarkable progress in targeted and immune‐directed therapies for other solid organ malignancies. Poly (ADP‐ribose) polymerase inhibitors (PARPi) are effective anticancer drugs that produce good initial clinical responses, especially in homologous recombination DNA repair‐deficient cancers. However, resistance is the rule rather than the exception, and recurrent tumors tend to have an aggressive phenotype associated with poor survival. Many efforts have been made to overcome PARPi resistance, mostly by targeting genes and effector proteins participating in homologous recombination that are overexpressed during PARPi therapy. Due to many known and unknown compensatory pathways, genes, and effector proteins, overlap and shared resistance are common. Overexpression of programmed cell death‐ligand 1 (PD‐L1) and cancer stem cell (CSC) sparing are novel PARPi resistance hypotheses. Although adding programmed cell death‐1 (PD‐1)/PD‐L1 inhibitors to PARPi might improve immunogenic cell death and be crucial for durable responses, they are less likely to target the CSC population that drives recurrent tumor growth. Lysine‐specific histone demethylase‐1A and histone deacetylase inhibitors have shown promising activity against CSCs. Combining epigenetic drugs such as lysine‐specific histone demethylase‐1A inhibitors or histone deacetylase inhibitors with PARPi/anti‐PD‐1/PD‐L1 is a novel, potentially synergistic strategy for priming tumors and overcoming resistance. Furthermore, such an approach could pave the way for the identification of new upstream epigenetic and genetic signatures.