Late Tumor Recurrence Research Articles

Postpubertal-Type Teratoma of the Retroperitoneal Space as a Late Recurrence of a Testicular Germ Cell Tumor: A Case Report With Clinical Insight

Postpubertal-Type Teratoma of the Retroperitoneal Space as a Late Recurrence of a Testicular Germ Cell Tumor: A Case Report With Clinical Insight

Treatment of Primary Cardiac Tumors in Children: A Single Center 18-Year Experience.

This study aimed to compare the clinical characteristics and courses of pediatric patients with cardiac tumors in nonoperative and operative groups to help guide treatment decisions. We reviewed the medical records of patients diagnosed with primary pediatric cardiac tumors at our institution between 2003 and 2020. Demographic data, clinical characteristics, and follow-up data between the operation and nonoperation groups were compared. A total of 56 patients were included in the study. Thirteen patients underwent surgery. The median age was 1.4 months (range, 1 to 18 years). The patients in the operation group had more frequent symptoms or signs, such as desaturation, respiratory difficulty, murmur, a higher mass area/chamber area (MC) ratio, decreased ventricular contractility, and significant ventricular outflow tract obstruction (VOTO). An MC ratio of 0.568 was the cutoff value for differentiating patients with symptoms or signs of heart failure and decreased ventricular contractility. At the last follow-up, all patients had good ventricular contractility except one patient in the operative group with fibroma. In the non-operative group, rhabdomyomas often regressed spontaneously, while fibromas often increased in size. Two patients in the nonoperative group died. In the operative group, there was no early or late mortality or tumor recurrence. In this study, patients had good outcomes with or without surgery, even when the tumor was large, or surgery was performed in early infancy.

Abstract PO2-20-09: Hiding in plain sight: A heterogeneous response in a patient with metastatic HR+/HER2- breast cancer

Abstract INTRODUCTION: Metastatic breast cancer is an infamously heterogeneous disease—characterized by a range of clinical presentations and treatment responses. In light of this heterogeneity, ASCO guidelines recommend patients with new, accessible metastatic tumors undergo a biopsy to inform treatment decisions. Here, we present a patient with HR+/HER2- disease with a long history of unusually heterogeneous responses—and a repeat metastatic biopsy that provided an answer. CASE: A 55-year-old woman presented for consultation of treatment-refractory metastatic breast cancer. She was originally diagnosed with a right-sided Stage III HR+/HER2- invasive ductal carcinoma (IDC) at the age of 33. Upon staging, she was incidentally found to have a right lower-lobe lung carcinoid tumor that was removed by lobectomy. She underwent a partial mastectomy, axillary lymph node dissection, followed by adjuvant chemo- and radiation therapy. She tolerated one week of tamoxifen which was discontinued due to adverse effects. Fifteen years later, screening mammography revealed a suspicious lesion in the right breast—biopsy consistent with a new IDC. She underwent bilateral mastectomies which showed a pT1cNxM0 G2 IDC with associated DCIS (ER+/PR+/HER2 IHC 2+, FISH-negative, Oncotype RS 12). Genetic testing was negative. The patient trialed adjuvant tamoxifen, which was discontinued due to repeat adverse effects. Two years later, rising tumor markers prompted restaging scans that demonstrated an enlarging liver lesion. Liver biopsy was consistent with metastatic adenocarcinoma of the breast (ER+/PR+/HER2 IHC 0), GATA3 positive. Patient was started on letrozole with lupron and palbociclib with disease control for two years until progression in the bone, prompting a switch of letrozole to fulvestrant with continued palbociclib. Her disease was stable for two additional years until progression of multiple liver lesions. She was then started on single-agent paclitaxel. At this point, she was seen in our office for consultation and next-line therapy options. Repeat staging scans showed heterogeneous response in the liver with overall progression. ctDNA testing revealed a mutation in MEN1 (p.Q354*, 2.8% VAF) without other actionable alterations. Patient opted to enroll into a clinical trial of an experimental ER-antagonist but experienced progression of her liver lesions on first staging scans. A second liver biopsy was performed on a progressive lesion which showed ER-/PR-/HER2- disease. She opted to enroll into a Phase 1b/2 trial with sacituzumab govitecan-hziy in combination with a PARPi. Staging scans again showed a mixed response in the liver. Given a history of mixed responses and discordant receptor staining, the differential diagnosis included loss of hormone receptor expression in the breast carcinoma versus metastases from an occult neoplasm. Additional immunohistochemical studies were performed on a subsequent liver biopsy showing positivity for chromogranin, synaptophysin, and INSM1, and negative results for ER, PR, GATA3, and TRPS1. Next-generation sequencing of the progressive lesion revealed a MEN1 SNV (p.Q354*, VAF 82%) as well as loss of 11q (MEN1 locus) suggestive of biallelic loss of MEN1—providing molecular evidence of a metastatic carcinoid tumor. A history of mixed response in the liver was concluded to be two coexisting neoplasms—a metastatic HR+/HER2- breast cancer as well as a late recurrence of a right-lower lobe carcinoid tumor from 22 years prior. DISCUSSION: The unanticipated discovery of an occult, coexisting neoplasm in the setting of a metastatic HR+/HER2- breast cancer illustrates the value of meticulous pathological review, repeat molecular testing and the use of next-generation diagnostic tools such as tumor sequencing in the advanced setting—particularly when a clinical story defies conventional expectations—to personalize care and optimize oncologic management in the face of complex biology. Citation Format: Nolan Priedigkeit, Jane Brock, Olivia Cunningham, Molly Skeffington, Melissa Hughes, Nancy Lin, Susan Lester, Heather Parsons. Hiding in plain sight: A heterogeneous response in a patient with metastatic HR+/HER2- breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-20-09.

Major Histocompatibility Class-I (MHC-I) downregulation in glioblastoma is a poor prognostic factor but not a predictive indicator for treatment failure

BackgroundMHC-I expression is a crucial factor in cancer immunity, and its regulations can impact tumor progression and recurrence. The mechanism through which glioblastoma use MHC-I to avoid immunosurveillance has been rarely investigated. MethodsA retrospective cohort of 35 patients with IDH-mutant WHO-Grade 4 astrocytoma and IDH-wildtype glioblastoma were examined for MHC-I using protein and gene expression assays. The association between IDH mutation, TP53 mutation, and MHC-I expression with recurrence-free interval were investigated. ResultsThe average patients’ age was 49.6 year. IDH was wildtype in 13 tumors. MHC-I protein expression was absent in 30 tumors, faint in 4 tumors, and membrane bound dense expression in single tumor. MHC-I expression was upregulated in 10 tumors and 25 tumors showed MHC-I downregulation. P53 was positively expressed in 19 cases and lost in 13 cases. A significant statistical difference was observed in the RFI between tumors with distinct MHC-I expression and IDH-mutation [p-value = 0.008]. IDH-wildtype tumors with upregulated MHC-I expression showed late tumor recurrence compared to IDH-wildtype tumors with downregulated MHC-I expression. There was insignificant statistical difference in RFI among patients with varying degree of MHC-I expression, who received TMZ or TMZ and other chemotherapies [P-value = 0.44] ConclusionsGlioblastoma with upregulated MHC-I showed a delayed tumor recurrence in comparison to those with downregulated MHC-I expression. However, downregulated MHC-I may not necessarily be an indicator of poor problems.

The synergistic effect of IDH mutation and NDRG-2 dysregulation in the progression of WHO-grade 4 astrocytomas

BackgroundNDRG2 is a tumour suppressor gene involved in tumor growth inhibition. Its effect on tumour recurrence remains controversial. The aim of this study is to explore the dual effect of IDH mutation and NDRG2 dysregulation in WHO-Grade 4 astrocytoma recurrence. MethodsA group of 36 patients with WHO-Grade 4 astrocytoma were examined for NDRG2 expression using protein and gene expression assays. The relationship between IDH, NDRG2 protein and gene expressions, and recurrence-free interval [RFI] was explored. ResultsThe mean patients age in this study was 45-years with 21 males and 15 females. IDH was mutant in 22 tumors. NDRG2 protein expression was low in 23 tumors, and high in 13 tumors. NDRG2 gene expression was upregulated in 4 tumors and 32 tumors showed NDRG2 gene downregulation. The consistency between two tasting methods of NDRG2 expression was 52.8%. There was a significant statistical difference in RFI among tumors with varying NDRG2 gene expression and IDH mutation [p-value= 0.021]. IDH-mutant tumours with downregulated NDRG2 expression showed late recurrence compared to IDH-wildtype glioblastoma. ConclusionsIDH-mutant WHO Grade-4 astrocytoma with downregulated NDRG2 gene are associated with late tumor recurrence. IDH mutations cause excessive accumulation of D-2-hydroxyglutarate, that may inhibit the activity of TET proteins, potentially leading to DNA hypermethylation and gene silencing.

Tumor Recurrence versus Radiation-induced Stroke in a Child with a History of Medulloblastoma

Children with a history of central nervous system neoplasia, submitted to radiotherapy, have an increased risk of vascular complications that can be, clinically and imagiologically, very similar to a tumor recurrence. We describe the case of an 11-year-old child who, 10 years after diagnosis and treatment of a medulloblastoma, suddenly developed right hemiparesis. The initial imaging findings did not allow the exclusion of tumor recurrence, making a differential diagnosis with recent ischemic injury. Due to clinical and imaging worsening, the patient started chemotherapy, suspended after the first cycle, due to clear neurological improvement. One month after the onset of symptoms, patient was clinically stable, having undergone a new magnetic resonance imaging, revealing a chronic evolution of the lesion, suggestive of a vascular etiology. This case explores the differential diagnosis of late tumor recurrence in children undergoing radiotherapy, highlighting the importance of etiological identification in therapeutic guidance.

Dynamic interplay between corticosteroid treatment and the role of SRC-1 gene dysregulation in the progression of WHO-Grade 4 Astrocytoma

BackgroundCorticosteroid is commonly used before surgery to control cerebral oedema in brain tumours and is frequently continued throughout treatment. Its long-term effect of on the recurrence of WHO-Grade 4 astrocytoma remains controversial. The interaction between corticosteroid, SRC-1 gene and cytotoxic T-cells has never been investigated.MethodsA retrospective cohort of 36 patients with WHO-Grade 4 astrocytoma were examined for CD8 + T-cell and SRC-1 gene expressions through IHC and qRT-PCR. The impact of corticosteroid on CD8+T-cells infiltration, SRC-1 expression, and tumour recurrence was analyzed.ResultsThe mean patients age was 47-years, with a male to female ratio 1.2. About 78% [n = 28] of the cases showed reduced or no CD8+T-cell expression while 22% [n = 8] of cases have showed medium to high CD8+T-cell expression. SRC-1 gene was upregulated in 5 cases [14%] and 31 cases [86%] showed SRC-1 downregulation. The average of total days and doses of administered corticosteroid from the preoperative period to the postoperative period was at range of 14–106 days and 41–5028 mg, respectively. There was no significant statistical difference in RFI among tumours expressing high or low CD8+T-cells when corticosteroid was administered in recommended or exceeded doses [p-value = 0.640]. There was a significant statistical difference in RFI between CD8+T-Cell expression and SRC-1 gene dysregulation [p-value = 002]. Tumours with high CD8+T T-cell expression and SRC-1 gene downregulation had late recurrence.ConclusionsCorticosteroid treatment can directly affect the SRC-1 gene regulation but does not directly influence cytotoxic T-cells infiltration or tumor progression. However, SRC-1 gene downregulation can facilitate late tumor recurrence.

Laser interstitial thermal therapy in the treatment of brain metastases: the relationship between changes in postoperative magnetic resonance imaging characteristics and tumor recurrence.

Laser interstitial thermal therapy (LITT) has been used to treat brain metastases (BMs) in several countries, and its safety and effectiveness have been confirmed. In most cases, magnetic resonance imaging (MRI) reveals an increase in tumor volume with an enhanced margin after LITT. However, little is known about the relationship between this MRI change and tumor recurrence. We report the first case series of BMs treated by LITT in China to evaluate the clinical characteristics and predictive factors of tumor recurrence. Patients with less than four brain metastatic lesions and a Karnofsky performance status (KPS) > 70 were eligible for study inclusion. Standard LITT procedures were performed, and a follow-up MRI was performed to analyze the radiographic changes, especially the volume ratio of the enhanced margin and the whole lesion on MRI at 30days postoperatively. All the volume-related data were delineated and calculated using 3D Slicer software. Related predictors were also collected to evaluate the correlation with local tumor control. Eighteen patients with nineteen lesions were enrolled for treatment and follow-up. Primary tumor histology included pulmonary carcinoma (n = 11) and breast cancer (n = 4). On average, the tumor size measured 3.01 cm3 (range, 0.40-7.40 cm3), the total ablation time was 13.58min (range, 2.88-37.15min), and the complete ablation rate was 92.4% (range, 29.2-100%). Comparing 3s0-day follow-up MRI results with preoperative MRI findings, 18 lesions showed a 2.28-fold (range, 1.21-4.88) volume increase; all the lesions displayed an enhanced component with a volume ratio of 42.35% (range, 10.14-100%). Five patients experienced tumor recurrence, and the local tumor control rates at 90days and 180days of follow-up were 68.4% and 66.7%, respectively. Univariate analysis indicated that the primary tumor, ablation rate, and enhanced volume ratio (EVR) > 40% in the 30-day MRI were associated with tumor recurrence, whereas multivariate analysis showed that only EVR > 40% was a predictive factor of local control. LITT is a minimally invasive method used to ablate brain metastases which can be used as the first-line treatment for BM patients under certain indications. After LITT, most tumors showed volume enlargement on the 30-day MRI scan, and EVR > 40% on the 30-day MRI may indicate late tumor recurrence.

The effect of chemotherapies on the crosstalk interaction between CD8 cytotoxic T-cells and MHC-I peptides in the microenvironment of WHO grade 4 astrocytoma.

CD8 + T-cells and MHC-I have been detected in brain gliomas with a significant outcome. The effect of chemotherapies on the crosstalk interaction between CD8 + T-cells and MHC-I has never been explored. The protein expression profiling of CD8 cytotoxic T-cells and the gene expression assay of MHC-I in 35 patients diagnosed with WHO grade 4 astrocytoma were performed. The impact of these two factors on tumor recurrence was analyzed. IDH was wildtype in 13 tumors. MHC-I protein expression was absent or low in 34 tumors and dense in a single case. MHC-I gene expression was upregulated in 10 tumors and 25 tumors showed MHC-I gene downregulation. Temozolomide (TMZ) was given to 24 patients and 11 patients received TMZ plus other chemotherapies. No statistically significant association was observed between IDH mutation and CD8 + T-cells ( p = 0.383). However, this association was significant in recurrence-free interval (RFI) ( p = 0.012). IDH-wildtype tumors with highly infiltrated CD8 + T-cells or IDH-mutant tumors with low CD8 + T-cells showed late tumor recurrence. There was a statistically significant difference in RFI between tumors with different MHC-I expression and CD8 + T-cell counts after treatment with TMZ or TMZ plus ( p = 0.026). No association between IDH mutation and CD8+ cytotoxic T-cell was found. IDH is directly linked to tumor recurrence regardless of CD8 + T-cells infiltration. TMZ plus other adjuvants is proved to be more effective in improving patient survival and delaying tumor recurrence, as compared to using TMZ alone. Nonetheless, none-TMZ adjuvants may increase tumor sensitization to cytotoxic T-cells more than TMZ.

Efficacy of Obturator Nerve Block During Transurethral Resection on Non-muscle invasive Intermediate and High Risk Lateral Wall Bladder Tumours: A Prospective Randomized Controlled Study.

We aimed to investigate the effects of obturator nerve block (ONB) on obturator reflex, incomplete resection, perforation, progression and recurrence of tumor, presence of muscle tissue in the specimen, need for a second transurethral resection (TURBT) of bladder tumors, and postoperative complications in patients who underwent TURBT for intermediate-high risk lateral wall non-muscle invasive bladder cancers (NMIBC). Patients were assigned to one of two groups by drawing lots: ONB or none ONB. Early and late recurrence, tumor progression, obturator reflex beat, incomplete resection, perforation, presence of muscle layer in pathology, second TURBT application, operation time, postoperative hospital stay, and complications were compared between the two groups. The median follow-up time of the study was32 (23-41) months. Interquartile range (IQR) was 9. Tumor recurrence at the 3rd month cystoscopy controls was observed in 5 (9.8%) patients in the ONB group, while it was observed in 11 (20.8%) patients in the nONB group (p=0.01). Late tumor recurrence was observed in 10 patients (19.6%) in the ONB group, and in 20 patients (37.7%) in the nONB group (p=0.041). The RFS rate at 12th month was 84% in the ONB group, 69% in the nONB group, 79% in the ONB group at 36th month, and 58% in the nONB group at 36 months, the PFS rate was 94% in the ONB group, while it was 85% in the nONB group (p=0.041). Our study showed that ONB decrease the early and late recurrence and increase recurrence free survival in patients with intermediate-high risk lateral wall bladder cancer.

Adult-Type Granulosa Cell Tumor, an Unusual Site of Recurrent Tumor at The Sigmoid Colon: A Case Report and Literature Review

Granulosa cell tumor constitutes approximately 1% of all ovarian tumors. Extraovarian spread can occur as a late recurrence. The authors reported a case of 41-year-old woman with adult-type granulosa cell tumor at sigmoid colon. The patient visited the outpatient department for a yearly medical check-up with no specific complaints. She had a history of ovarian cystectomy 12 years prior. A mass in left pelvic cavity was revealed upon transvaginal ultrasonography and computer tomography (CT). At the time of laparoscopy, a well-defined subserosa mass was detected at the antimesenteric side of the sigmoid colon. The right and left ovaries appeared grossly normal. The tumor was successfully removed with laparoscopic sigmoidectomy. The pathologic findings were that of adult-type granulosa cell tumor, which was corresponding to the previous diagnosis made in the ovarian cystectomy specimen 12 years ago. The authors presented this case as an example of late recurrence of ovarian granulosa cell tumor in sigmoid colon, which could potentially be mistaken as other usual colonic tumors in the absence of previous history of ovarian tumor. Keywords: Colonic granulosa cell tumor; Extraovarian granulosa cell tumor; Sex cord-stromal tumor

LGG-15. Late mortality and morbidity of adult survivors of childhood glioma treated across three decades: a report from the Childhood Cancer Survivor Study

PURPOSE: Pediatric low-grade glioma therapy has evolved to delay or eliminate radiation. The impact of therapy changes on long-term outcomes remains unknown. METHODS: Cumulative incidence of late mortality (death >5 years from diagnosis), subsequent neoplasms (SNs), and chronic health conditions (CHCs, CTCAE grading criteria) were evaluated in the Childhood Cancer Survivor Study among 5-year survivors of glioma diagnosed 1970-1999. Outcomes were evaluated by diagnosis decade and by treatment exposures received ≤5 years following diagnosis (surgery-only, chemotherapy ± surgery, and cranial radiation ± surgery or chemotherapy). Relative risk (RRs) with 95%CIs estimated long-term outcomes using multivariable piecewise exponential models. RESULTS: Among 2,684 eligible survivors (age at diagnosis (median [range]), 7 years [0-20 years]; time from diagnosis, 24 years [5-48 years]), exposure to cranial radiation decreased [51% (1970s), 45% (1980s), 25% (1990s)] along with late tumor recurrence (>5 & ≤15 years from diagnosis) [9.8% (1970s), 8.8% (1980s), 5.0% (1990s)]. The 15-year cumulative incidence of late mortality was 10.3% (1970s), 6.5% (1980s), and 6.0% (1990s) (p<0.001, comparison of cumulative incidence curves). The 15-year cumulative incidence of grade 3-5 CHCs was 19.7% (1970s), 17.8% (1980s), and 14.2% (1990s) (p<0.0001). A reduction in SN incidence was not observed. In multivariable analyses excluding treatment exposure, later diagnosis (1990s vs. 1970s) was associated with lower risk of late mortality, grade 3-5 CHCs and SNs. Inclusion of treatment exposure in the model attenuated the effect of diagnosis decade. Radiation or chemotherapy exposure increased risk compared to surgery alone for late mortality (radiation RR 4.95, 95%CI 3.79-6.47; chemotherapy RR 2.88, 95%CI 1.85-4.48), CHCs (radiation RR 4.02, 95%CI 3.28-4.94; chemotherapy RR 1.66, 95%CI 1.13-2.45), and SNs (radiation RR 4.02, 95%CI 3.06-6.13, chemotherapy RR 2.08, 95%CI 1.03-4.23)). CONCLUSION: Late mortality and CHCs decreased in childhood glioma survivors diagnosed from 1970-1999 largely due to therapy changes, particularly avoidance of cranial radiation, without increased late recurrence.

Impact of Time to Recurrence on Survival Outcome of Salvage Liver Transplantation

BackgroundSalvage liver transplantation (SLT) is the ideal treatment for patients with recurrent hepatocellular carcinoma (HCC) and liver cirrhosis. The optimal timing for offering SLT was controversial. This study aimed at investigating the impact of time to recurrence and other prognostic factors on survival outcome after SLT. MethodsBetween May 2000 and April 2019, patients who had undergone hepatectomy or ablation for HCC and later received SLT in Queen Mary Hospital were included. Clinico-pathological data during primary treatment and SLT were retrospectively reviewed. Kaplan–Meier analysis and log-rank test were used to determine overall and disease-free survival after SLT. Prognostic factors affecting overall and disease-free survival were determined by multivariate analysis using Cox regression analysis. P-value of less than 0.05 was considered statistically significant. ResultsFifty-three patients were identified within the specified period including 22 patients in early recurrence group (ER group, time to recurrence within 1 year) and 31 patients in late recurrence group (LR group, time to recurrence more than 1 year). The 1-, 5-, and 10-year overall survival after primary treatment was 100%, 76.6%, and 61.1% in the ER group and 100%, 90%, and 76.4% in the LR group (p = 0.59). There were no statistical differences in overall survival (p = 0.84) and disease-free survival (p = 0.85) after SLT between ER and LR group. Pre-transplant alpha-fetoprotein > = 400 ng/mL (p = 0.007) and macrovascular invasion in explant (p = 0.002) were independent risk factors for shorter overall survival after primary treatment. ConclusionTime to recurrence after primary treatment of HCC did not affect survival outcome after SLT. With careful patient selection, SLT could be offered to patient with early or late tumor recurrence.

Comparison of long-term survivals following hepatectomy for hepatocellular carcinoma according to the time-point of recurrence and treatment modalities for recurrent disease

Abstract Objective Disease recurrence following curatively intended hepatectomy for hepatocellular carcinoma (HCC) limits oncologic outcome. Based on the extent, location and time-point of tumor recurrence, different therapeutic modalities are available to treat recurrent HCC. Therefore, our aim was to investigate the role of these treatments and the time-point of recurrence on long-term survival. Methods Clinicopathological data of patients, who underwent hepatectomy for HCC at a major hepatobiliary center in Switzerland between 2012 and 2019, were assessed. Patients suffering tumor recurrence were stratified according to the treatment modalities for recurrent HCC including surgical treatment (repeat hepatectomy or liver transplantation), interventional treatment, and conservative treatment (chemotherapy or best supportive care). Groups were compared regarding to overall survival (OS). Additionally, long-term outcomes were compared between patients with early (≤ 12 months) and late (&amp;gt; 12 months) tumor recurrence. Results During the study period, 159 patients underwent hepatectomy for HCC. Median follow-up time was 53 months. After a median time of seven (1-64) months, 74 patients were diagnosed with tumor recurrence (47 %). The majority of patients developed early recurrence (n = 49) and 58 patients had intrahepatic recurrence only. Treatment options were re-resection, liver transplantation, interventional methods, and palliative therapy in 5, 15, 23, and 31 patients, respectively. Surgical treatment was significantly associated with improved OS compared to interventional and conservative treatment (5-year OS: 84% vs. 39% vs. 30%, p &amp;lt; 0.0001). OS was significantly better among patients with late recurrence compared to patients with early recurrence, irrespective of the treatment modality used for the recurrent disease (5-year OS: 70% vs. 38%, p = 0.008). Conclusion Repeat hepatectomy or liver transplantation for recurrent HCC following hepatectomy is associated with better long-term survival compared to interventional or conservative therapies, especially for patients with late tumor recurrence. Patients with intrahepatic HCC recurrence should be evaluated according to the extent of tumor burden, liver function, and functional status to identify the best candidates for a surgical treatment.

The Impact of IDH1 Mutation and MGMT Promoter Methylation on Recurrence-Free Interval in Glioblastoma Patients Treated With Radiotherapy and Chemotherapeutic Agents.

The aim of this study is to investigate the relationship between isocitrate dehydrogenase-1 (IDH1) mutation and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation with recurrence-free interval in glioblastoma patients treated with chemoradiotherapies. Clinical data were collected from 82 patients with totally resected glioblastoma and treated with adjuvant therapies from 2014 to 2019. IDH1 mutation was assessed by immunohistochemistry and MGMT promoter methylation was assessed by different sequencing methods. IDH1 mutation was present in 32 cases and 50 cases were IDH1 wildtype; 54 and 28 patients had unmethylated and methylated MGMT promoter, respectively, Of the 82 patients, 62 patients received chemoradiotherapy while 20 patients only received radiation. Approximately, 61% of patients had a tumor recurrence after 1 year, and 39% showed a recurrence before 1 year of treatment. There was no significant relationship between IDH1 mutation and MGMT promoter methylation (p-value = 0.972). Patients with IDH1 mutation and their age <50 years showed a significant difference in recurrence-free interval (p-value = 0.014). Difference in recurrence-free interval was also statistically observed in patients with unmethylated MGMT promoter and treated with chemoradiotherapies (p-value = 0.031), by which they showed a late tumor recurrence (p-value = 0.016). This revealed that IDH1 mutation and MGMT methylation are independent prognostic factors in glioblastoma. Although IDH1-mutant glioblastomas showed late tumor recurrence in patients less than 50 years old, the type of treatment modalities may not show additional beneficial outcome. Patients with unmethylated MGMT and IDH1 mutation, treated with different chemoradiotherapies, showed a late tumor recurrence.

Postoperative Trends and Prognostic Values of Inflammatory and Nutritional Biomarkers after Liver Transplantation for Hepatocellular Carcinoma

Simple SummaryInflammatory biomarkers have a strong prognostic value in surgically treated patients with hepatocellular carcinoma (HCC), but the underlying pathogenic mechanism has not been completely clarified. Conversely, nutritional biomarkers predict the outcomes after hepatic resection for HCC but not after liver transplantation (LT). Indeed, the impact of LT on the recipient’s nutritional status is heterogeneous, while the data on the patient’s outcome after LT in terms of inflammatory status are limited. Therefore, to address these unsolved questions, we conducted a retrospective analysis on 324 HCC patients treated with LT, exploring the postoperative trend up to 1 year post-LT and the prognostic value of the Platelet-to-Lymphocyte Ratio (PLR), Neutrophil-to-Lymphocyte Ratio (NLR), Controlling Nutritional Status (CONUT), Prognostic Nutritional Index (PNI). It was found that at 1 year post-LT, the nutritional status of liver-transplanted HCC patients significantly improved while their inflammatory state tended to persist. Consequently, post-LT PLR and NLR maintained a prognostic value for LT outcome while post-LT CONUT and PNI acquired it.Preoperative inflammatory biomarkers such as the Platelet-to-Lymphocyte Ratio (PLR) and the Neutrophil-to-Lymphocyte Ratio (NLR) strongly predict the outcome in surgically treated patients with hepatocellular carcinoma (HCC), while nutritional biomarkers such as the Controlling Nutritional Status (CONUT) and the Prognostic Nutritional Index (PNI) show an analogue prognostic value in hepatic resection (HR) but not in liver transplant (LT) cases. Data on the impact of LT on the inflammatory and nutritional/metabolic function are heterogeneous. Therefore, we investigated the post-LT trend of these biomarkers up to postoperative month (POM) 12 in 324 HCC patients treated with LT. Inflammatory biomarkers peaked in the early post-LT period but at POM 3 leveled off at values similar (NLR) or higher (PLR) than pre-LT ones. CONUT and PNI worsened in the early post-LT period, but at POM 3 they stabilized at significantly better values than pre-LT. In LT recipients with an overall survival >1 year and no evidence of early HCC recurrence, 1 year post-LT NLR and PNI independently predicted patient overall survival, while 1 year post-LT PLR independently predicted late tumor recurrence. In conclusion, at 1 year post-LT, the nutritional status of liver-transplanted HCC patients significantly improved while their inflammatory state tended to persist. Consequently, post-LT PLR and NLR maintained a prognostic value for LT outcome while post-LT CONUT and PNI acquired it.

Inflection of Akt/mTOR/STAT-3 cascade in TNF-α induced protein 8 mediated human lung carcinogenesis

Lung cancer is the leading cause of cancer-related death across the globe. Despite the marked advances in detection and therapeutic approaches, management of lung cancer patients remains a major challenge to oncologists which can be mainly attributed to late stage diagnosis, tumor recurrence and chemoresistance. Therefore, to overthrow these limitations, there arises a vital need to develop effective biomarkers for the successful management of this aggressive cancer type. Notably, TNF-alpha induced protein 8 (TIPE), a nuclear factor-kappa B (NF-κB)-inducible, oncogenic molecule and cytoplasmic protein which is involved in the regulation of T lymphocyte-mediated immunity and different processes in tumor cells such as proliferation, cell death and evasion of growth suppressors, might serve as one such biomarker which would facilitate effective management of lung cancer. Expression studies revealed this protein to be significantly upregulated in different lung cancer types, pathological conditions, stages and grades of lung tumor compared to normal human lung tissues. In addition, knockout of TIPE led to the reduced proliferation, survival, invasion and migration of lung cancer cells. Furthermore, TIPE was found to function through modulation of Akt/mTOR/STAT-3 signaling cascade. This is the first report which shows the involvement of TIPE in tobacco induced lung carcinogenesis. It positively regulated nicotine, NNK, NNN, and BaP induced proliferation, survival and migration of lung cancer cells possibly via Akt/STAT-3 signaling. Thus, this protein possesses important role in the pathogenesis of lung tumor and hence it can be targeted for developing newer therapeutic interventions for the clinico-management of lung cancer.

Efficacy and safety of flexible endoscopic intervention via laryngeal mask airway for endobronchial hamartoma removal

Objective To evaluate the clinical characteristics, efficacy and safety of flexible endoscopic intervention for endobronchial hamartoma. Material and methods Thirteen patients with endobronchial hamartoma who underwent flexible endoscopic intervention at a single center were analyzed retrospectively. The clinical characteristics and efficacy of flexible endoscopic intervention were described. Results Nine patients were cured after one single flexible endoscopic intervention, three patients underwent second flexible endoscopic interventions due to late tumor recurrence, while one patient who eventually became stable with a 40% stenosis of the airway lumen, received a third intervention because of two relapses. Pneumothorax occurred in one patient who was cured after oxygen therapy. There were no serious complications such as massive hemorrhage, airway perforation, airway ignition and suffocation associated with the therapy. Conclusions Flexible endoscopic intervention appeared to be safe and effective for the treatment of patients with endobronchial hamartoma.

Is follow-up still mandatory more than 5 years after surgery for colorectal cancer?

The aim of this study was to assess if to prolong follow-up (FU) more than 5years after surgery for colorectal cancer (CRC) is justified or not. Patients who underwent surgery for a CRC before 2013 and without any tumor recurrence (or synchronous metastases) during the first 5years after surgery were identified from our database and included. Between 1996 and 2012, 121 patients operated for rectal (RC) (median of FU of 84months; range 60-211) and 97 with colonic cancer (CC) (median of FU of 78months; range 60-139), without any tumor recurrence (or synchronous metastases) during the first 5years after surgery, presented a late tumor recurrence: 13/121 RC (10.7%) versus 2/97 CC (2.1%) (p = 0.014); 8/13 recurrences in RC (61.5%) were observed after neoadjuvant radiochemotherapy, and 9/13 (69.2%) in pN0 tumors. Among the 13 recurrences, 3 had both local and metastatic recurrences (23%), 5 an isolated local recurrence (38.5%) and 5 an isolated metastatic recurrence (38.5%). After surgery for CC, the 2 recurrences were observed in patients with T3N0 tumors. After surgery for a CRC, in patients without tumor recurrence during the first 5years after surgery, follow-up after 5years must be continued in rectal cancer patients because of a 10.7% rate of late recurrence. On the opposite, after surgery for colon cancer the 2% rate of late recurrence after 5years suggested that only patients with pT3-T4 colonic cancer could probably be followed more than 5years after surgery.

Primary osteosarcoma in elderly patients: A report of three cases.

Osteosarcoma is the most common type of primary malignant bone tumor in children and young adults. However, primary osteosarcoma in elderly patients is rare. The present study reports 3 cases of advanced osteosarcoma in elderly patients. The pathological findings in all 3 cases confirmed the diagnosis of primary osteosarcoma. Notably, each patient received different treatment options. Chemoradiotherapy was recommended in case 1 due to the age of the patient. However, the patient requested to be discharged and was lost to follow-up. Conversely, in case 2, the 62-year-old female patient underwent systemic chemotherapy, but no surgical treatment, and in case 3, the 51-year-old male patient underwent complete tumor resection and received systemic chemotherapy for late tumor recurrence. Early diagnosis of osteosarcoma in elderly patients is difficult, and misdiagnosis or a missed diagnosis is common. In clinical practice, bone tumors in elderly patients should be investigated carefully. Imaging examinations are essential for diagnosis, and biopsy is required for confirmation. However, the efficacy of chemotherapy for elderly patients with primary osteosarcoma remains uncertain. Collectively, due to the small number of reports of osteosarcoma in the elderly population, the 3 cases in the present study raise awareness of this rare condition.