Treatment Of Recurrent Tumors Research Articles

High cellular plasticity state of medulloblastoma local recurrence and distant dissemination.

Medulloblastoma (MB), a heterogeneous pediatric brain tumor, poses challenges in the treatment of tumor recurrence and dissemination. To characterize cellular diversity and genetic features, we comprehensively analyzed single-cell/nucleus RNA sequencing (sc/snRNA-seq), single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq), and spatial transcriptomics profiles and identified distinct cellular populations in SHH (sonic hedgehog) and Group_3 subgroups, with varying proportions in local recurrence or dissemination. Local recurrence showed higher cycling tumor cell enrichment, whereas disseminated lesions had a relatively notable presence of differentiated subsets. Chromosomal alteration evaluation revealed distinct genetic subclones during MB progression, such as chr7q gain and chr11 loss in Group_3 disseminations. A subpopulation termed "high cellular plasticity (HCP)" emerged during MB progression and was associated with increased dividing potential and chromatin accessibility, contributing to recurrence. Inhibiting HCP-associated markers, like protein tyrosine phosphatase receptor type Z1 (PTPRZ1), efficiently suppressed MB progression in preclinical models. These findings address critical gaps in understanding the cellular diversity, chromosomal alterations, and biological dynamics of recurrent MB, offering potential therapeutic insights.

Protocol for open-label, randomised, controlled trial of intensive surveillance vs. standard postoperative follow-up in patients undergoing surgical resection for oesophageal and gastric cancer (SARONG trial).

TPS416 Background: Despite recent improvements in oncological and surgical treatment for patients with oesophageal and gastric cancer, 60% of patients with locally advanced disease who are treated with a curative intent will develop tumour recurrence and die within three years of completing treatment. In the absence of robust scientific evidence national or international guidelines have failed to reach consensus on the optimal surveillance strategy after primary treatment of oesophageal or gastric cancer. Methods: The primary research question of the proposed randomised controlled trial (RCT) is does the routine use of a structured follow-up program with regular radiological and endoscopic investigations improve survival in patients who have had surgical treatment for oesophageal or gastric cancer with curative intent? We aim to assess whether structured follow-up, including radiological and endoscopic investigations after completing curatively intended treatment, improves survival in patients with oesophageal or gastric cancer. The secondary aims of this RCT are to determine the impact of a structured post-treatment surveillance upon the detection and treatment of cancer recurrence and health-related quality of life, including anxiety and to assess the cost-effectiveness. We will undertake a national prospective, multi-centre, randomised controlled trial of structured follow-up including radiological and endoscopic investigations versus standard clinical follow-up. The setting will be at least 24 large oesophago-gastric cancer UK cancer centres. We will aim to recruit 952 oesophageal and gastric cancer patients receiving surgical resection for curatively intended treatment of oesophageal or gastric cancer +/- neoadjuvant/adjuvant chemo(radio or immuno)therapy. At 4-12 weeks after surgery for oesophageal or gastric cancer, patients will be assessed for eligibility for inclusion in the trial. Patients will be randomised 1:1 to receive either intensive follow-up for up to 3-years, with clinical and computerised tomography (CT) investigation every 6 months, and an endoscopy at 12 months or to current standard NHS follow-up, i.e. clinical review at 6 and 12 months followed by targeted investigation as required based upon the onset of new symptoms. The primary outcome is 3-year all-cause mortality and secondary outcomes include health-related quality of life (including anxiety), 3-year disease-specific mortality, pattern and treatment of tumour recurrence, and cost-effectiveness of follow-up in both study arms. The findings of this RCT will inform national and international guidelines for patients with oesophageal and gastric cancer, as this will be the first RCT to provide robust evidence concerning the value of surveillance in this population. Clinical trial information: 14417629.

Denosumab salvage therapy in an 11-year-old boy with locally recurrent unresectable giant cell tumor of the lumbar spine after surgery

Giant cell tumors (GCTs) of the bone are locally aggressive primary bone tumors with a benign character. Spinal involvement is rare which accounts for approximately 5% of all primary bone tumors and it is quite rare in the lumbar spine. An 11-year-old boy patient presented with pain of low back and bilateral low extremities. Lumbar CT and MRI revealed a lytic lesion of the L4 vertebra corpus. The patient earned remarkable and timely recovery with 2 surgical interventions and the use of denosumab. Surgical resection for GCTs is still preferable as the initial treatment, denosumab should be utilized after tumor resection whether based on the purpose of prevention or treatment of tumor recurrence.

The role of liquid biopsy in the diagnosis of glioblastoma progression

Purpose: to summarize available data on the diagnostic value of various circulating biomarkers for the detection of glioblastoma recurrence. Material and Methods. A literature search was conducted using PubMED ExoCarta and SILVA databases. Results. Glioblastoma multiforme (GBM) is the most common glioma in adults with an unfavorable prognosis. Treatment of tumor recurrence can improve the survival of patients. Neuroimaging is the standard method of diagnosing brain tumor recurrence. However, a neuroimaging method to clearly distinguish between pseudo progression and tumor progression has not been found to date. Current molecular tumor profling relies heavily on tissue resection or biopsy. Tissue profling has several disadvantages in the central nervous system’s tumors, including the challenge associated with invasive biopsy, the heterogeneous nature of many malignancies where a small biopsy can under represent the mutational profle. Liquid biopsy is a promising method in diagnosing malignant tumors. Blood collection is a simple, minimally invasive procedure, but cerebrospinal fuid allows tumor markers to be detected more confdently. However, collection of cerebrospinal fuid is a complex and invasive procedure that can be accompanied by serious complications. Conclusion. Biological fuid markers such as circulating tumor cells, extracellular vesicles, cell-free DNA and cell-free RNA allow for the detection of GMB, determination of molecular genetic features of cancer during response to therapy, and early detection of GBM recurrence.

Abstract 3710: Synergistic cell death induction in ovarian cancer by cisplatin and ABT-199 is mediated by expression of NOXA

Abstract Ovarian cancer is among the top ten leading causes of cancer death in women worldwide with a mortality rate of roughly 5% among all cancer deaths. So far, there are no recommended screening tests for the early detection of ovarian cancer. Therefore, patients are frequently diagnosed at late stages of ovarian cancer, which is associated with unfavorable 5-year survival. Patients suffering from ovarian cancer often show a good response to initial therapy with platinum-based compounds and/or taxanes subsequent to resection of the affected tissue. Unfortunately, ovarian cancer shows a high frequency of relapse and after chemotherapy persistent tumor cells re-expand and successively evolve into therapy-resistant tumors. We recently reported that cisplatin (cisPt) treatment of ovarian cancer cells enhances mitochondrial content and mitochondrial reactive oxygen species (Kleih et al. 2019). We therefore speculated that the enhanced mitochondrial content primes cisPt-treated cells for apoptosis induced by BH3 mimetic drugs, such as Venetoclax (ABT-199), that act on anti-apoptotic Bcl-2 proteins at the outer mitochondrial membrane. To explore this hypothesis, we investigated whether the combined administration of cisPt and ABT-199 leads to a synergistic cell death induction in ovarian cancer cells with different cisPt resistance and mitochondrial content. Detection of cell death by flow cytometric measurements of the mitochondrial membrane potential and exposure of phosphatidylserine demonstrated a synergistic cell death induction by cisPt and ABT-199 in OVCAR4 and OVCAR8 cells, irrespective of the cisPt resistance. Interestingly, Western blot analysis revealed that ABT-199 induced the accumulation of the BH3-only protein NOXA in both cancer cell lines. Accumulation of NOXA was dependent on ABT-199-mediated activation of the stress-responsive transcription factor ATF4. Knock-down experiments showed that apoptosis of cisPt-resistant OVCAR8 cells by the combined treatment with ABT-199 and cisPt was entirely dependent on NOXA. Moreover, also cisPt-sensitive OVCAR4 cells revealed an initially reduced apoptosis induction by the NOXA knock-down. Our data therefore elucidate the molecular mechanism of the synergistic efficacy of cisPt/ABT-199 combination therapies, which should be promising especially for the treatment of recurrent tumors developing reduced sensitivity to cisPt-based treatments. Citation Format: Benjamin Schaefer, Sandra Weller, Tobias B. Beigl, Klaus Schulze-Osthoff, Hans-Georg Kopp, Walter E. Aulitzky, Frank Essmann. Synergistic cell death induction in ovarian cancer by cisplatin and ABT-199 is mediated by expression of NOXA [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 3710.

Oncologic follow-up in head and neck cancer patients

Despite medical treatment according to evidence-based guidelines, approximately 25-30% of all head and neck tumor patients suffer adisease relapse, depending on tumor stage and entity. The primary goal of systematic follow-up examinations is early detection and treatment of recurrent tumors or metachronous secondary tumors, but it also serves to rule out distant metastasis. Secondary goals are the diagnosis and management of treatment-associated side effects to optimize quality of life. Because of an especially high relapse risk in the first 2years after treatment, close-knit clinical controls are recommended, e.g., quarterly. Later on, the clinical control interval can be extended to 6months. Cross-sectional diagnostic imaging of the primary tumor region is performed annually and when screening for possible distant metastases, or upon clinical suspicion of recurrence. After 5years without tumor recurrence, the structured clinical follow-up is usually completed.

The role of extracellular vesicles in the diagnosis of glioblastoma progression

The article reviews studies highlighting the role of extracellular molecules in non-invasive diagnosis of glioblastoma recurrence. Glioblastoma is the most common malignant tumor of the brain characterized by fatal outcome prognosis. Current treatment of tumor recurrence allows to increase patient survival, improve functional outcome and decrease caregivers» load. The standard method of recurrence diagnosis is neuroimaging which at early stages cannot distinguish between tumor recurrence and post-radiation changes. Currently in oncology, liquid biopsy and marker detection in circulating extracellular vesicles are considered promising approaches allowing to obtain early and differential tumor diagnosis, determine dynamic molecular and genetic status of the tumor, diagnose tumor recurrence at early stages. In this context, the most promising approach to glioblastoma diagnosis is associated with studying of expression of glial fibrillary acidic protein (GFAP), epidermal growth factor receptor (EGFR), its mutant variant EGFRvIII, podoplanin (PDPN) and isocitrate dehydrogenase 1 (IDH1) in extracellular vesicles; for primary glioblastoma diagnosis and early recurrence: studying of microRNA-210, -301a, -222, -123-3p, -21; for control of immunotherapy effectiveness in patients with recurrent forms of glioblastoma after standard treatment: evaluation of СD9+ / GFAP+ / survivin+ exosomes in plasma.

Radiotherapy for patients with locoregional and oligometastatic relapses of prostate cancer after radical prostatectomy

Materials and methods. In our study, 21 patients with recurrent prostate cancer after radical prostatectomy and oligometastases were treated by salvage radiation therapy, which included radiotherapy treatment of recurrent tumors, regional pelvic lymph nodes, the prostate bed and stereotactic body radiation therapy to detected solitary metastases.Results. The average follow-up period was 19 ± 3.5 months. At the same time, 12 (57 %) of 21 patients are currently under observation for more than 1 year, and 1 patient for more than 5 years without signs of a biochemical recurrence. The indicator of biochemical control of the disease was 86 % (18 / 21 patients) with an average follow-up period of 19 months.Conclusion. It seems to us that further study of this problem can replace today's palliative standard of treatment for this special category of patients — hormonal and chemotherapy treatment, which has low effectiveness at a high incidence of toxicity.

The clinical outcome of recurrent sacral chordoma with further surgical treatment.

Case series.To analyze the clinical results and related factors of further surgical treatment for recurrent sacral chordomas.Chordomas are rare primary malignant tumors with a high recurrence rate. The treatment of recurrent tumors is difficult and controversial. Contamination by previous operations and disturbed local anatomical structures may increase the risk of reoperation. Most previous studies have focused on the primary tumor; there are very few reports on the clinical diagnosis, treatment, and prognosis of recurrent sacral chordomas.Thirty-four patients with recurrent sacral chordomas from 1979 to 2014 were included in this study. The patients comprised 25 men and 9 women with an average age of 50.7 (24–75) years. The average time until recurrence was 19.4 (4–51) months postoperatively, and 85.3% of the recurrent tumors were located in bone. The patients had an average of 1.2 (1–3) recurrences before further operations were performed in our hospital. The mean maximum tumor diameter was 8.1 (4.6–12.0) cm. Thirty-one patients underwent further tumor resection in our hospital. The postoperative recurrence, metastasis, and survival results were followed and analyzed.The mean follow-up after surgical treatment of recurrence was 49.6 (12–144) months. Nine patients (37.5%) developed recurrence again after an average of 26.7 months. The 3-year and 5-year recurrence-free survival rate was 69.4% and 63.1%, respectively. Multivariate analysis showed that the tumor level within the sacrum (P = .001) and the surgical margin (P = .001) were significant recurrence-related factors. Four patients (16.7%) developed lung metastasis. Eighteen patients were alive at last follow-up. The 5-year and 10-year survival rate after surgical treatment of recurrence was 67.3% and 53.9%, respectively.Most recurrent tumors are located in bone, and a safe osteotomy margin is important. The surgical margin is the only controllable factor of further tumor recurrence. Some patients with recurrence achieve long survival and obtain a clinical benefit from repeated operations if complete resection is achieved.

THE VALUE OF PROGNOSTIC FACTORS FOR GLIOBLASTOMA TREATED WITH CONCURRENT THERMOCHEMORADIOTHERAPY

The treatment of patients with glioblastoma continues to be one of the greatest challenges. Glioblastoma is the most aggressive malignant primary brain tumor and is the most lethal among all cancers. Despite advances in the standard treatment, the prognosis for patients with glioblastoma remains poor, therefore, the development of novel treatment strategies is required.Material and methods.Our study included 30 patients with newly diagnosed glioblastoma, who underwent concurrent chemoradiotherapy and local hyperthermia.Results.The median disease-free and overall survival rates were 9.6 months and 23 months, respectively. The analysis of clinical, molecular-genetic and prognostic factors related to treatment modality showed statistically significant differences in survival between patient groups representing different times for starting adjuvant therapy after surgery. The median disease-free survival was significantly higher in patients who received chemoradiotherapy with local hyperthermia within 6 weeks after surgery than in patients who started adjuvant treatment earlier. The overall survival rate was statistically higher in patients receiving a special treatment for tumor recurrence compared to that in patients receiving symptomatic therapy. The evaluation of molecular-genetic prognostic factors showed no statistically significant differences in survival among patients with methylated and nonmethylated MGMT promoter. The presence of IDH1 mutations was identified in only one case. Evaluation of prognostic factors does not allow identification of clinical and molecular biological factors that group patients with hypersensitivity to the proposed treatment regimen. However, high rates of overall and disease-free survival, even in patients with non-methylated MGMT, allow us to recommend this treatment modality for patients with newly diagnosed glioblastoma.

Supratentorial Extraventricular Ependymoma: Retrospective Analysis of 15 Patients at a Single Institution

Supratentorial extraventricular ependymoma (STEE) is an extremely rare central nervous system (CNS) neoplasm, the clinical characteristics and optimal treatment of which remain unclear. We retrospectively analyzed the clinical characteristics and treatment outcomes of 15 patients with STEE. Fifteen patients with STEE were identified, and their clinical, radiologic, and surgical records were reviewed. The 15 patients included 6 males (40%) and 9 females (60%), with a median age of 15 years. Nine patients (60%) underwent gross total resection, 5 patients (33.3%) underwent subtotal resection, and 1 patient (6.7%) underwent biopsy. Eight patients received adjuvant radiotherapy, and 3 received adjuvant chemotherapy. The 5-year overall survival (OS) rates of patients with World Health Organization (WHO) grade II and grade III STEE were 100% and 30%, respectively, and the corresponding 2-year progression-free survival (PFS) rates were 77.8% and 20%. The differences in OS and PFS rates between WHO grades II and III STEE were statistically significant (P < 0.01 and 0.02, respectively). Anaplastic histology (WHO grade III) was a poor prognostic factor for PFS (P= 0.04). The recurrence pattern was local recurrence in all patients; all cases were treated primarily by redo surgery. Three patients with recurrent WHO grade II STEE were alive at more than 64, 52, and 44 months after redo surgery. STEE is an extremely rare CNS neoplasm. The histological grade of STEE is an important prognostic factor. Microsurgical resection might play a major role in both initial treatment and treatment of recurrent tumors.

What Is the Success of Repeat Surgical Treatment of a Local Recurrence After Initial Wide Resection of Soft Tissue Sarcomas?

Treatment for patients with locally recurrent soft tissue sarcomas after wide resection is challenging, and few studies have examined the results of treating these patients. In treatment of recurrent tumors, it has been reported that positive margins are correlated to local rerecurrence, but the relationship between surgical margin and survival remains controversial and risk factors for local recurrences after wide resection of soft tissue sarcomas are not well established. This study examined clinical outcomes and factors associated with survival and local rerecurrence in patients with local recurrence after initial surgical treatment who underwent another resection with a goal of negative margins. The purpose of this study was to determine (1) oncologic outcomes (survival rates and local rerecurrence-free rates) of surgical treatment for patients with local recurrence after wide resection; (2) whether factors associated with survival and local rerecurrence-free rates can be determined; and (3) the proportion of patients treated by amputation at final followup. Between 1992 and 2013, we treated 530 patients with soft tissue sarcoma without metastasis. Of those, 26 (5%) were lost before 3 years of followup but were not known to have died. Of the remainder, 59 have had a local recurrence. Of those with a local recurrence, 34 (58%) were treated with wide resection, whereas 25 (42%) were treated with nonsurgical treatment including chemotherapy and radiotherapy. During that period, our general indications for wide resection were patients (1) without distant metastasis; or (2) without distant lymph node metastasis, and contraindications were distant organ metastasis and/or distant lymph node metastasis. Of those treated with wide resection, 30 (88%) were available for followup. We conducted a retrospective analysis of these 30 patients with local recurrence (17 men, 13 women) who had previously undergone wide resection. Patient followup ranged from 1 to 12 years (median, 5 years). Survivorship (including overall survival and survival free from repeat recurrence) was ascertained by the Kaplan-Meier method. Factors associated with survival were evaluated by the log-rank test. Amputations were performed when limb-sparing surgery was deemed unsuitable because of extensive involvement of the limb by tumor, including invasion of multiple muscle compartments and neurovascular components. Survivorship free from amputation was ascertained by the Kaplan-Meier method. Overall 5- and 10-year Kaplan-Meier survival rates after resection were 70% (95% confidence interval [CI], 50%-91%) and 44% (95% CI, 12%-76%), respectively, and 12 patients (40%) developed distant metastases after the second operation. Ten patients (33%) had additional local recurrences, and overall 5- and 10-year local rerecurrence-free rates were 66% (95% CI, 48%-85%) and 50% (95% CI, 18%-81%), respectively. A positive margin was associated with further recurrence (5-year local rerecurrence-free rates of positive margin: 20% [95% CI, 0%-52%], negative margin: 89% [95% CI, 74%-100%], p < 0.01) and with survival (5-year survival rates of positive margin: 36% [95% CI, 0%-75%], negative margin: 91% [95% CI, 74%-100%], p < 0.01). The survival rate was lower in patients with recurrence developing after 2 years (5-year survival rates of within 2 years: 46% [95% CI, 2%-90%], after 2 years: 83% [95% CI, 62%-100%], p = 0.01). The overall 5- and 10-year amputation-free rates were 86% (95% CI, 74%-99%) and 81% (95% CI, 67%-96%), respectively. A surgical procedure with negative margins appears to be important for reducing the likelihood of local recurrences and improving survival of patients with rerecurrence after wide resection of soft tissue sarcomas. Although these findings need to be confirmed in larger studies, it appears that when tumor recurrence is evident within 2 years from the primary surgery, it is associated with a poor prognosis. Local recurrence within 2 years after wide resection may also be an indicator of aggressive tumor biology. Level IV, therapeutic study.

Clinical and genetic analysis of recurrent adult-type granulosa cell tumor of the ovary: Persistent preservation of heterozygous c.402C>G FOXL2 mutation.

BackgroundAdult-type granulosa cell tumors of the ovary (aGCTs) are rare tumors that represent 2–5% of ovarian malignancies. The prognosis of this tumor is favorable, and it is characterized by slow progression. 10–30% of these tumors recur after 4–7 years of the primary surgery and the 5-year survival rate from the first recurrence is 55%, for the incompletely resected patients. At this time, complete resection is the only prognostic factor for better outcome, and establishing a novel strategy for identification and/or treatment of recurrent tumors is crucial. After the discovery of heterozygous c.402C>G FOXL2 mutations in 97% of cases of aGCT, much effort has been made to find the role of the mutation on the pathogenesis of aGCT, however, little is known about the role of the mutation in disease progression.MethodsWe analyzed the clinical data of 56 aGCT patients to find a marker of recurrence. In particular, we compared the FOXL2 status in 5 matched primary and recurrent samples by immunohistochemistry, and TaqMan allelic discrimination assay to address the role of FOXL2 in potential mechanisms of recurrence.ResultsThe clinical data analysis was consistent with complete resection as an indicator of disease eradication, though the sample size was limited. The genetic analysis showed all the samples, including recurrent tumor samples up to 14 years after the primary surgery, expressed heterozygous c.402C>G FOXL2 mutation and the FOXL2 protein expression.ConclusionThis report describes the preservation of heterozygous c.402C>G FOXL2 mutation in recurrent aGCTs. This finding adds further credence to the concept that the c.402C>G FOXL2 mutation is oncogenic and integral to this disease.

A case of long-term survival after surgical resection for solitary adrenal recurrence of esophageal squamous carcinoma

BackgroundEsophageal carcinomas are highly malignant tumors with a high frequency of lymph node and distant organ metastasis. Treatment for recurrent tumors is generally decided on an individual basis. Although multidisciplinary treatments involving chemotherapy, surgical resection, and radiation are performed, the prognosis remains poor. Here, we report a case of prolonged recurrence-free survival (38 months) after esophageal carcinoma surgery and subsequent laparoscopic adrenalectomy for right adrenal metastasis.Case presentationAn 83-year-old man was diagnosed with type 3 esophageal squamous cell carcinoma (T3N1M0, cStage IIIA, UICC-7), spreading from the lower thoracic esophagus to the abdominal esophagus. He underwent thoracoscopic esophagectomy with a two-field lymph node dissection followed by substernal gastric tube reconstruction. The final diagnosis was moderately differentiated squamous cell carcinoma (T3N2M0, fStage IIIB). Adjuvant chemotherapy was not administered because of the advanced age and postoperative condition of the patient. Computed tomography (CT) at 14 months postoperatively showed a mass with a 2-cm diameter at the right adrenal gland. Positron emission tomography (PET)/CT revealed a high fluorodeoxyglucose (FDG) uptake in the mass. It was suspected that the mass was a metastatic lesion secondary to the primary esophageal carcinoma. No metastases to lymph nodes or other distant organs were identified. The patient underwent laparoscopic right adrenalectomy. The histopathological examination revealed moderately differentiated squamous cell carcinoma, suggesting metastasis from the primary esophageal carcinoma. He has survived without recurrence for 38 months since laparoscopic adrenalectomy to remove the right adrenal metastastic mass after the esophageal carcinoma surgery.ConclusionsWe describe a very elderly male who survived laparoadrenalectomy for right adrenal metastasis following esophageal cancer surgery without recurrence for 38 months postoperatively. Therefore, surgical resection might be an option for solitary adrenal recurrence.

EP-1413: IORT for treatment of recurrent tumors - A single institution analysis

EP-1413: IORT for treatment of recurrent tumors - A single institution analysis

Reoperative endoscopic endonasal surgery for residual or recurrent pituitary adenomas.

OBJECTIVE Regrowth of the lesion after surgical removal of pituitary adenomas is uncommon unless subtotal resection was originally achieved in the first surgery. Treatment for recurrent tumor can involve surgery or radiotherapy. Locations of residual tumor may vary based on the original approach. The authors evaluated the specific sites of residual or recurrent tumor after different transsphenoidal approaches and describe the surgical outcome of endoscopic endonasal transsphenoidal reoperation. METHODS The authors analyzed a prospectively collected database of a consecutive series of patients who had undergone endoscopic endonasal surgeries for residual or recurrent pituitary adenomas after an original transsphenoidal microscopic or endoscopic surgery. The site of the recurrent tumor and outcome after reoperation were noted and correlated with the primary surgical approach. The chi-square or Fisher exact test was used to compare categorical variables, and the Mann-Whitney U-test was used to compare continuous variables between surgical groups. RESULTS Forty-one patients underwent surgery for residual/recurrent pituitary adenoma from 2004 to 2015 at Weill Cornell Medical College. The previous treatment was a transsphenoidal microscopic (n = 22) and endoscopic endonasal (n = 19) surgery. In 83.3% patients (n = 30/36) there was postoperative residual tumor after the initial surgery. A residual tumor following endonasal endoscopic surgery was less common in the sphenoid sinus (10.5%; 2/19) than it was after microscopic transsphenoidal surgery (72.7%; n =16/22; p = 0.004). Gross-total resection (GTR) was achieved in 58.5%, and either GTR or near-total resection was achieved in 92.7%. Across all cases, the average extent of resection was 93.7%. The rate of GTR was lower in patients with Knosp-Steiner Grade 3-4 invasion (p < 0.0005). Postoperative CSF leak was seen in only one case (2.4%), which stopped with lumbar drainage. Visual fields improved in 52.9% (n = 9/17) of patients and were stable in 47% (n = 8/17). Endocrine remission was achieved in 77.8% (n = 14/18) of cases, 12 by surgery alone and 2 by adjuvant medical (n = 1) and radiation (n = 1) therapy. New diabetes insipidus occurred in 4.9% (n = 2/41) of patients-in one of whom an additional single anterior hormonal axis was compromised-and 9.7% (n = 4/41) of patients had a new anterior pituitary hormonal insufficiency. CONCLUSIONS Endonasal endoscopic reoperation is extremely effective at removing recurrent or residual pituitary adenomas that remain after a prior surgery, and it may be preferable to radiation therapy particularly in symptomatic patients. Achievement of GTR is less common when lateral cavernous sinus invasion is present. The locations of residual/recurrent tumor were more likely sphenoidal and parasellar following a prior microscopic transsphenoidal surgery and sellar following a prior endonasal endoscopic surgery.

CD55 is a HIF-2α marker with anti-adhesive and pro-invading properties in neuroblastoma.

CD55 has been revealed to have an important role in tumor genesis, and presence of small populations of cells with strong CD55 expression would be sufficient to predict poor prognosis of several tumors. In our study we revealed that CD55 is a novel target of hypoxia-inducible factor HIF-2α in neuroblastoma (NB) cells. We show that HIF-2α expression is sufficient to sustain stem-like features of NB cells, whereas CD55 protein upon HIF-2α expression contributes to growth of colonies and to invasion of cells, but not to stemness features. Interestingly, in NB tissues, CD55 expression is limited to quite a small population of cells that are HIF-2α positive, and the gene expression of CD55 in the NB data set reveals that the presence of CD55high affects prognosis of NB patients. The functional characterization of CD55-positive populations within heterogeneous NB monoclonal cell lines shows that CD55 has pro-invading and anti-adhesive properties that might provide the basis for the ability of solid tumors to survive as microscopic residual disease. The easy accessibility to CD55 membrane antigen will offer the possibility of a novel antibody approach in the treatment of recurrent tumors and will provide a ready target for antibody-based visualization in NB diagnosis and prognosis.

Anti-tumor enhancement of Fei-Liu-Ping ointment in combination with celecoxib via cyclooxygenase-2-mediated lung metastatic inflammatory microenvironment in Lewis lung carcinoma xenograft mouse model.

BackgroundFei-Liu-Ping (FLP) ointment is an oral prescription medication that has been widely applied to treat lung cancer patients in China. Regulation of the metastatic microenvironment is an important therapeutic approach for prevention and treatment of tumor recurrence and metastasis. The advantage of Traditional Chinese Medicine management of lung cancer lies in the prevention of recurrence and metastasis. Our previous study has demonstrated that FLP ointment could regulate lung inflammatory microenvironment in vitro. However, the effects of FLP on the tumor microenvironment in vivo are still poorly understood. The objective of this study is to investigate the effect of FLP alone or in combination with celecoxib in the prevention of lung cancer progression by Cyclooxygenase (Cox)-2 mediated tumor inflammatory microenvironment in vivo.Methods120 Lewis lung carcinoma xenograft mice were divided equally into four groups: vehicle, FLP, celecoxib, and FLP plus celecoxib. The dynamic growth of the xenografted tumors was observed using an in vivo fluorescence imaging system. Mice were sacrificed on day 14, day 21, and day 28, and tumor specimens and lung tissues were harvested to detect the metastasis-associated protein expression.ResultsTumor inhibition rate was 15.4, 44.2, 47.4 % at day 14, 37.3, 34.7, 61.5 % at day 21, and 15.5, 10.3, 32.5 % at day 28 after treatment of FLP, celecoxib, and FLP plus celecoxib, respectively. Upon treatment of FLP and celecoxib together, lung metastasis rate was 30 % (8 metastatic nodules) lower than other groups. FLP inhibited Cox-2 expression in a time-dependent manner. Moreover, FLP inhibited N-cadherin, matrix metalloproteinases (MMP)-9, and Vimentin expression. Treatment of FLP in combination with celecoxib was more effective than FLP or celecoxib alone in inhibiting vascular endothelial growth factor, platelet-derived growth factor receptors β, microsomal Prostaglandin E synthase-1, MMP-2, MMP-9, N-cadherin, and Vimentin expression, but increased E-cadherin expression.ConclusionsFLP inhibited tumor growth and metastasis in a Lewis lung xenograft mice model through the Cox-2 pathway. FLP in combination with celecoxib enhanced the antitumor growth and anti-metastasis effects. Traditional Chinese herbs combined with anti-inflammatory drugs might offer a promising strategy to prevent tumor metastasis.

Recurrence of hepatocellular cancer after resection: patterns, treatments, and prognosis.

We sought to determine the factors associated with survival after recurrence of hepatocellular cancer (HCC) after resection and the outcome of our prospectively applied treatment protocol. Very little is known about the prognosis of HCC that recurs after resection and the outcomes associated with treatments applied to recurrent tumors. A total of 661 HCC patients undergoing resection from January 1988 to January 2011 were reviewed to identify those with recurrence. Single recurrences with preserved liver function, and no portal hypertension were treated with resection. Patients with multiple intrahepatic tumors or poor liver function and no major comorbidities were listed for transplantation. Patients with up to 3 tumors, each 4 cm or smaller, and not eligible for transplantation, received ablation. Patients not eligible for ablation received embolization. Other treatments such as systemic therapy and radiation were used in remaining patients, but not in a systematic manner. Recurrent HCC developed in 356 (54%) patients at a median time of 22 months from primary resection. Median survival from time of recurrence to death was 21 months. Variables independently associated with survival from recurrence included time from primary resection to recurrence, alpha-fetoprotein more than 100 ng/mL at recurrence, recurrent tumor larger than 3 cm, BCLC stage at recurrence, and type of treatment rendered for the recurrence. All variables except treatment modality were significantly correlated with characteristics of the original primary tumor. Most of the variables associated with outcome after recurrence are linked to the primary tumor at initial presentation. Nevertheless, meaningful survival can be achieved with appropriate treatment of recurrent tumors.

Abstract T P366: Moyamoya Following Treatment of Intracranial Tumors

Introduction: We present our experience with the management of patients initially diagnosed with intracranial tumor who subsequently developed moyamoya following tumor treatment. Hypothesis: We hypothesized that moyamoya associated with brain tumors would demonstrate similar radiographic findings and response to surgery as idiopathic moyamoya and that radiotherapy would increase stroke risk. Methods: Single institution series reviewing all moyamoya cases from 1985-2014 to identify those initially diagnosed with intracranial tumor who subsequently developed moyamoya. Results: 26 patients (12M/14F) diagnosed with 27 intracranial tumors later developed moyamoya. Average age at tumor diagnosis was 4.6yr (range 0.5 - 14.7) and 9.8yr at moyamoya diagnosis (range 5.0 - 19.7). 21 tumors had radiotherapy, 16 chemotherapy, and 14 surgical resection, 2 of whom underwent surgery alone without adjuvant therapy. Radiotherapy patients had moyamoya diagnosed 3.9yr after radiation (range 0.2 - 13.8). All patients (100%) presenting with stroke had radiation. Initial moyamoya symptoms included TIA (58%), stroke (42%), and seizure (19%); moyamoya was incidental discovery in 23%. 13 patients (50%) had stroke on imaging; their average Suzuki grade was 3. 45 pial synangiosis were performed, 19 with bilateral surgery. Postoperative complications included stroke in 2 patients (4.4% per operation). 2 patients had a stroke during follow up unrelated to moyamoya but rather from small vessel disease in the brain stem resulting from radiotherapy. Postoperative arteriograms demonstrated Matsushima grade A/B collaterals in 75% of patients studied (n=24 hemispheres). Eight patients required further treatment for tumor recurrence or progression. Conclusions: In conclusion, pediatric brain tumor patients develop moyamoya arteriopathy clinically and radiographically similar to idiopathic moyamoya. Radiotherapy is associated with increased incidence of radiographic stroke in this cohort. Secondary injury from radiation may occur in the posterior fossa, but ischemia from moyamoya in the cerebral hemispheres can be corrected with revascularization conferring durable protection from stroke.