Larger Tumor Volume Research Articles

Retrobulbar Hemangioblastomas in von Hippel-Lindau Disease: Clinical Course and Management.

Retrobulbar hemangioblastomas involving the optic apparatus in patients with von Hippel-Lindau disease (VHL) are rare, with only 25 reported cases in the literature. To analyze the natural history of retrobulbar hemangioblastomas in a large cohort of VHL patients in order to define presentation, progression, and management. Clinical history and imaging of 250 patients with VHL in an ongoing natural history trial and 1774 patients in a neurosurgical protocol were reviewed. The clinical course, magnetic resonance images, treatment, and outcomes were reviewed for all included patients. A total of 18 patients with retrobulbar hemangioblastoma on surveillance magnetic resonance imaging met the inclusion criteria for this study. Of the 17 for whom clinical information was available, 10 patients presented with symptoms related to the hemangioblastoma, and 7 were asymptomatic. The mean tumor volume was larger for symptomatic (810.6 ± 545.5 mm3) compared to asymptomatic patients (307.6 ± 245.5 mm3; P <.05). A total of 5 of the symptomatic patients were treated surgically and all experienced improvement in their symptoms. All 3 symptomatic patients that did not undergo intervention had continued symptom progression. Long-term serial imaging on asymptomatic patients showed that these tumors can remain radiographically stable and asymptomatic for extended periods of time (101.43±71 mo). This study suggests that retrobulbar hemangioblastomas may remain stable and clinically asymptomatic for long durations. Recent growth and larger tumor volume were associated with symptom occurrence. Surgical treatment of symptomatic retrobulbar hemangioblastomas can be safe and may reverse the associated symptoms.

Prevalence and outcome of comorbidities associated with acromegaly.

Acromegaly is associated with various comorbidities, such as arterial hypertension (aHT), type 2 diabetes mellitus (DM2), obstructive sleep apnoea syndrome (OSAS), carpal tunnel syndrome (CTS) and polyposis coli. For therapeutic decisions, it is essential to know if, and to what extent, these associated morbidities are reversible or preventable. The aim of this study is to assess the prevalence and course of aHT, obesity, OSAS, CTS, DM2 and polyposis coli in acromegalic patients. The following criteria for inclusion in this database study were used: treatment for acromegaly at the authors' institutions; full endocrinological and radiological work- and follow-up; screening for aHT, DM2, CTS, OSAS, obesity and polyposis coli. All patients were followed-up for > 3months, and treatments were indicated with the intent of biochemical remission (normal IGF-1 and random growth hormone level). Sixty-three patients were included. Twelve (19%), 45 (71%) and 6 (10%) patients harboured micro-, macro- and giant adenomas, respectively. Nineteen tumours (30%) invaded the cavernous sinus. Mean tumour volume was 5.4 cm3. Mean follow-up time was 42months. Sixty-one (97%) patients had transsphenoidal surgery; two patients only had drug therapy. Surgery led to remission in 31 (51%) patients. Intracavernous growth and larger tumour volume were negative predictors for cure. Drug therapy lead to remission in 22 (73%) patients within a mean follow-up of 54months. The pretherapeutic prevalence of associated morbidities was as follows: aHT, 56%; DM2, 25%; OSAS, 29%; CTS, 29%; polyposis coli, 5%. There were neither age nor gender preferences for the respective prevalences. Surgery leads to remission of aHT and DM2 in 6% and 25%, respectively. Additional drug therapy resulted in remission of aHT, DM2 and CTS in 17%, 14% and 14%, respectively. Other associated morbidities persisted regardless of therapeutic efforts. Even if criteria for remission were not met, no new comorbidities of acromegaly developed during follow-up. Treating acromegaly may relieve threatening associated morbidities such as aHT and DM2; nevertheless, only few comorbidities are reversible, which highlights the importance of treating acromegaly as early as possible.

Abstract IA-024: Sirt2: A tumor suppressor or promotor?

Abstract SIRT2, an NAD+-dependent histone deacetylase, has been shown to play a pivotal role in various physiological processes, however, its role in cancer is currently controversial. In recent years, SIRT2 has been described as both a tumor suppressor and oncogene with divergent expression and function in various malignancies. Using murine xenograft melanoma models, our results suggest increased systemic expression of SIRT2 promotes tumor progression. In this study, SIRT2-overexpressing mice exhibited enhanced tumor growth and larger tumor volumes compared to their wild-type littermates. Mechanistically, systemic overexpression of SIRT2 reduces the number of tumor-infiltrating natural killer (NK) cells and suppresses NK cell activation and proliferation within tumor microenvironment (TME). Furthermore, despite the effect of increased tumor growth rate and tumor volume in wild-type littermate mice, NK cell depletion does not affect that in SIRT2-overexpressing mice. Lastly, pharmacological inhibition of SIRT2 increases NK cell tumor infiltration and suppresses melanoma tumor growth in mice. The findings of this study identify a dynamic functional interaction between systemic SIRT2 and NK cell activity, which promotes melanoma tumor progression. Given the recent renewed interest in NK-cell-mediated immunotherapy response, SIRT2 could present a new opportunity to mediate immunotherapy response and resistance. Citation Format: Fen Xia. Sirt2: A tumor suppressor or promotor? [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr IA-024.

Radioactive Parathyroid Adenomas on Sestamibi Scans: Low Parathyroid Hormone Secretory Potential and Large Volume.

BackgroundWe investigated the clinical characteristics of parathyroid adenomas according to radioactivity on 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) single-photon emission computed tomography/computed tomography (SPECT/CT) in primary hyperparathyroidism (PHPT) patients.MethodsThe study included 217 patients diagnosed with PHPT from 2000 to 2019 at Seoul National University Hospital who underwent 99mTc-MIBI SPECT/CT scans. On SPECT/CT, the radioactivity of parathyroid adenomas was measured as the ratio of the mean radioactivity count of the parathyroid adenoma to that of the contralateral thyroid.ResultsTumors were localized by MIBI scans in 190 patients (MIBI [+] group) and by ultrasound or parathyroid four-dimensional CT in 27 patients (MIBI [−] group). The mean age was 55 years, and mean body mass index was 23.4 kg/m2. Patients in the MIBI (+) group had higher parathyroid hormone (iPTH) and lower 25-hydroxy vitamin D levels than those in the MIBI (−) group (168.0 pg/mL [interquartile range, IQR, 111.0 to 250.7] vs. 134.7 pg/mL [IQR, 98.2 to 191.2], P=0.049; 15.4 ng/mL [IQR, 11.1 to 20.8] vs. 21.2 ng/mL [IQR, 13.9 to 24.8], P=0.012, respectively). Patients in the MIBI (+) group had larger tumor volumes, but lower iPTH/volume ratios than those in the MIBI (−) group (1,216.66 [IQR, 513.40 to 2,663.02], 499.82 mm3 [IQR, 167.77 to 1,229.80], P=0.002; 0.18 [IQR, 0.08 to 0.46], 0.40 pg/mL/mm3 [IQR, 0.16 to 1.29], P=0.016, respectively). Adenoma radioactivity was positively correlated with calcium, iPTH, and volume (r=0.180, P=0.020; r=0.208, P=0.006; r=0.288, P<0.001, respectively), but not with iPTH/volume.ConclusionParathyroid adenomas with positive MIBI scans had larger volumes and higher iPTH than adenomas with negative scans, but lower iPTH per unit volume.

Senescence, immune microenvironment, and vascularization in cardiac myxomas

AimsCardiac myxomas are rare tumors of incompletely elucidated pathogenesis. The aim of this study is to explore the possible presence of a senescence phenotype in cardiac myxomas, associated with an inflammatory and vasculogenic tumor microenvironment. Methods and resultsThis is a retrospective study of 29 cardiac myxomas with immunohistochemical detection of various inflammatory, vascular, and senescence markers. We show that all myxomas contain tumor cells in senescence overexpressing p16, and a fraction of senescent endothelial cells. Macrophages are the principal inflammatory cell population, followed by cytotoxic T cells, with fewer plasma cells, mastocytes, and B lymphocytes. These populations are found in different intratumoral localizations. Larger tumor volume is associated with a lower percentage of myxoid matrix, higher cellularity, higher macrophage, and lower number of mast cells as well as higher PD-L1 expression by inflammatory cells. Higher vascular density is associated with higher percentage of B cells, a lower number of macrophages and higher number of mastocytes, and lower PD-L1 expression by inflammatory cells. Tumors with higher vascular density and higher cellularity show higher amounts of p16 senescent endothelial cells. ConclusionsMyxoma tumor cells are in senescence and reside inside a tumor microenvironment with a distinct inflammatory profile rich in macrophages and cytotoxic T cells, and a rich vasculature, probably attributed to a senescence-associated secretory phenotype.

Surgery after sunitinib administration to improve survival of patients with advanced pancreatic neuroendocrine neoplasms.

BackgroundLittle research is available regarding the treatments combining surgical resection with systemic chemotherapy for advanced pancreatic neuroendocrine neoplasm patients. We retrospectively elucidated whether sunitinib administration before surgery in advanced pancreatic neuroendocrine neoplasm (Pan‐NEN) patients increases survival.MethodsThis study included 106 of 326 Pan‐NEN patients with distant metastases and/or unresectable locally advanced tumors who visited our department to receive sunitinib for more than 1 mo during April 2002 to December 2019. Risk factors for overall survival (OS) and disease‐free survival (DFS) were analyzed.ResultsThe median duration of preoperative sunitinib administration and observation time after sunitinib were 6 and 26.5 mo, respectively. Of 106 patients, 31 (29.2%) underwent surgery following sunitinib administration. Hepatectomy, synchronous hepatopancreatectomy, pancreatectomy, and lymphadenectomy were performed for 13, 12, 5, and 1 patient, respectively. The 5‐y OS rates in the resected and nonresected groups were 88.9% and 14.1%, respectively (P < .001). In the multivariate analysis, the absence of surgical resection following sunitinib (hazard ratio [HR], 13.1; P = .001), poor differentiation (HR, 5.5; P = .007), and bilateral liver metastases (HR, 3.7; P = .048) were independent risk factors for OS, although large liver tumor volumes were more evident in the nonresected group, as patient characteristics. The median DFS was 16.1 mo in 22 patients who underwent R0/1 resections, and risk factors for postoperative recurrence were Ki‐67 index >7.8% (HR, 7.4; P = .02) and R1 resection (HR, 4.4; P = .04).ConclusionSurgical resection after sunitinib administration improved OS in advanced Pan‐NENs.

Role of Preoperative Assessment in Predicting Tumor-Induced Plasticity in Patients with Diffuse Gliomas.

When diffuse gliomas (DG) affect the brain’s potential to reorganize functional networks, patients can exhibit seizures and/or language/cognitive impairment. The tumor–brain interaction and the individual connectomic organization cannot be predicted preoperatively. We aimed to, first, investigate the relationship between preoperative assessment and intraoperative findings of eloquent tumors in 36 DG operated with awake surgery. Second, we also studied possible mechanisms of tumor-induced brain reorganization in these patients. FLAIR-MRI sequences were used for tumor volume segmentation and the Brain-Grid system (BG) was used as an overlay for infiltration analysis. Neuropsychological (NPS) and/or language assessments were performed in all patients. The distance between eloquent spots and tumor margins was measured. All variables were used for correlation and logistic regression analyses. Eloquent tumors were detected in 75% of the patients with no single variable able to predict this finding. Impaired NPS functions correlated with invasive tumors, crucial location (A4C2S2/A3C2S2-voxels, left opercular-insular/sub-insular region) and higher risk of eloquent tumors. Epilepsy was correlated with larger tumor volumes and infiltrated A4C2S2/A3C2S2 voxels. Language impairment was correlated with infiltrated A3C2S2 voxel. Peritumoral cortical eloquent spots reflected an early compensative mechanism with age as possible influencing factor. Preoperative NPS impairment is linked with high risk of eloquent tumors. A systematic integration of extensive cognitive assessment and advanced neuroimaging can improve our comprehension of the connectomic brain organization at the individual scale and lead to a better oncological/functional balance.

A High Postoperative Serum C-reactive Protein Level Has a Negative Impact on Long-term Survival, Regardless of Postoperative Infectious Complications, in Patients Who Undergo Laparoscopic Surgery for Colorectal Cancer.

We previously showed that an elevated postoperative serum C-reactive protein (CRP) level has a negative impact on long-term survival outcomes, regardless of the occurrence of infectious complications in colorectal cancer. However, the cause of postoperative inflammation could not be properly evaluated, because patient background factors, such as the surgical approach (open/laparoscopic), were not unified. A total of 277 patients who underwent laparoscopic surgery for stage II/III colorectal cancer were enrolled. The high-CRP group had lower relapse-free and overall survival rates in comparison to the low-CRP group. A high postoperative serum CRP level was significantly associated with a larger tumor diameter and longer operation time, and tended to be associated with a higher T stage and larger amount of bleeding. Larger tumor volume, longer operation time and larger amount of bleeding were associated with the promotion of postoperative inflammation, which worsened long-term survival outcomes in colorectal cancer.

In silico dosimetry of low-dose rate brachytherapy using radioactive nanoparticles

Purpose. Nanoparticles (NPs) with radioactive atoms incorporated within the structure of the NP or bound to its surface, functionalized with biomolecules are reported as an alternative to low-dose-rate seed-based brachytherapy. In this study, authors report a mathematical dosimetric study on low-dose rate brachytherapy using radioactive NPs. Method. Single-cell dosimetry was performed by calculating cellular S-values for spherical cell model using Au-198, Pd-103 and Sm-153 NPs. The cell survival and tumor volume versus time curves were calculated and compared to the experimental studies on radiotherapeutic efficiency of radioactive NPs published in the literature. Finally, the radiotherapeutic efficiency of Au-198, Pd-103 and Sm-153 NPs was tested for variable: administered radioactivity, tumor volume and tumor cell type. Result. At the cellular level Sm-153 presented the highest S-value, followed by Pd-103 and Au-198. The calculated cell survival and tumor volume curves match very well with the published experimental results. It was found that Au-198 and Sm-153 can effectively treat highly aggressive, large tumor volumes with low radioactivity. Conclusion. The accurate knowledge of uptake rate, washout rate of NPs, radio-sensitivity and tumor repopulation rate is important for the calculation of cell survival curves. Self-absorption of emitted radiation and dose enhancement due to AuNPs must be considered in the calculations. Selection of radionuclide for radioactive NP must consider size of tumor, repopulation rate and radiosensitivity of tumor cells. Au-198 NPs functionalized with Mangiferin are a suitable choice for treating large, radioresistant and rapidly growing tumors.

Early differences in dynamic uptake of 68Ga-PSMA-11 in primary prostate cancer: A test-retest study.

IntroductionDynamic PET/CT allows visualization of pharmacokinetics over the time, in contrast to static whole body PET/CT. The objective of this study was to assess 68Ga-PSMA-11 uptake in pathological lesions and benign tissue, within 30 minutes after injection in primary prostate cancer (PCa) patients in test-retest setting.Materials and methodsFive patients, with biopsy proven PCa, were scanned dynamically in list mode for 30 minutes on a digital PET/CT-scanner directly after an intravenous bolus injection of 100 MBq 68Ga-PSMA-11. Approximately 45 minutes after injection a static whole body scan was acquired, followed by a one bed position scan of the pelvic region. The scans were repeated approximately four weeks later, without any intervention in between. Semi-quantitative assessment was performed using regions-of-interest in the prostate tumor, bladder, gluteal muscle and iliac artery. Time-activity curves were extracted from the counts in these regions and the intra-patient variability between both scans was assessed.ResultsThe uptake of the iliac artery and gluteal muscle reached a plateau after 5 and 3 minutes, respectively. The population fell apart in two groups with respect to tumor uptake: in some patients the tumor uptake reached a plateau after 5 minutes, whereas in other patients the uptake kept increasing, which correlated with larger tumor volumes on PET/CT scan. Median intra-patient variation between both scans was 12.2% for artery, 9.7% for tumor, 32.7% for the bladder and 14.1% for the gluteal muscle.ConclusionDynamic 68Ga-PSMA-11 PET/CT scans, with a time interval of four weeks, are reproducible with a 10% variation in uptake in the primary prostate tumor. An uptake plateau was reached for the iliac artery and gluteal muscle within 5 minutes post-injection. A larger tumor volume seems to be related to continued tumor uptake. This information might be relevant for both response monitoring and PSMA-based radionuclide therapies.

Dosimetric impact of random spot positioning errors in intensity modulated proton therapy plans of small and large volume tumors

To study dosimetric impact of random spot positioning errors on the clinical pencil beam scanning proton therapy plans. IMPT plans of 10 patients who underwent proton therapy for tumors in brain or pelvic regions representing small and large volumes, respectively, were included in the study. Spot positioning errors of 1 mm, -1 mm or ±1 mm were introduced in these clinical plans by modifying the geometrical co-ordinates of proton spots using a script in the MATLAB programming environment. Positioning errors were simulated to certain numbers of (20%, 40%, 60%, 80%) randomly chosen spots in each layer of these treatment plans. Treatment plans with simulated errors were then imported back to the Raystation (Version 7) treatment planning system and the resultant dose distribution was calculated using Monte-Carlo dose calculation algorithm.Dosimetric plan evaluation parameters for target and critical organs of nominal treatment plans delivered for clinical treatments were compared with that of positioning error simulated treatment plans. For targets, D95% and D2% were used for the analysis. Dose received by optic nerve, chiasm, brainstem, rectum, sigmoid, and bowel were analyzed using relevant plan evaluation parameters depending on the critical structure. In case of intracranial lesions, the dose received by 0.03 cm3 volume (D0.03 cm3) was analyzed for optic nerve, chiasm and brainstem. In rectum, the volume of it receiving a dose of 65 Gy(RBE) (V65) and 40 Gy(RBE) (V40) were compared between the nominal and error introduced plans. Similarly, V65 and V63 were analyzed for Sigmoid and V50 and V15 were analyzed for bowel. The maximum dose variation in PTV D95% (1.88 %) was observed in a brain plan in which the target volume was the smallest (2.7 cm3) among all 10 plans included in the study. This variation in D95% drops down to 0.3% for a sacral chordoma plan in which the PTV volume is significantly higher at 672 cm3. The maximum difference in OARs in terms of absolute dose (D0.03 cm3) was found in left optic nerve (9.81%) and the minimum difference was observed in brainstem (2.48%). Overall, the magnitude of dose errors in chordoma plans were less significant in comparison to brain plans. The dosimetric impact of different error scenarios in spot positioning becomes more prominent for treatment plans involving smaller target volume compared to plans involving larger target volumes. Provides information on the dosimetric impact of various possible spot positioning errors and its dependence on the tumor volume in intensity modulated proton therapy.

Tumor microenvironment characterization in triple-negative breast cancer identifies prognostic gene signature

We aimed to elucidate the landscape of tumor microenvironment (TME) in triple-negative breast cancer (TNBC). Cohorts from Gene Expression Omnibus database (N = 107) and METABRIC (N = 299) were used as the training set and validation set, respectively. TME was evaluated via single-sample gene set enrichment analysis, and unsupervised clustering was used for cluster identification. Consequently, TNBC was classified into two distinct TME clusters (Cluster 1 and Cluster 2) according to predefined immune-related terms. Cluster 1 was characterized by low immune infiltration with poor prognosis; whereas, Cluster 2 was characterized by high immune infiltration with better survival probability. Further, Cluster 1 had larger tumor volumes, while Cluster 2 had smaller tumor volumes. Finally, a TME signature for prognosis stratification in TNBC was developed and validated. In summary, we comprehensively evaluated the TME of TNBC and constructed a TME signature that correlated with prognosis. Our results provide new insights for the immunotherapy of TNBC.

Predictors of recurrence and high growth rate of residual meningiomas after subtotal resection.

The extent of resection has been shown to improve outcomes in patients with meningiomas. However, resection can be complicated by constraining local anatomy, leading to subtotal resections. An understanding of the natural history of residual tumors is necessary to better guide postsurgical management and minimize recurrence. This study seeks to identify predictors of recurrence and high growth rate following subtotal resection of intracranial meningiomas. Adult patients who underwent primary surgical resection of a WHO grade I meningioma at a tertiary care institution from 2007-2017 were retrospectively reviewed. Volumetric tumor measurements were made on patients with subtotal resections. Stepwise multivariate proportional hazards regression analyses were performed to identify factors associated with time to recurrence, as well as stepwise multivariate regression analyses to assess for factors associated with high postoperative growth rate. Of the 141 patients (18%) who underwent radiographic subtotal resection of an intracranial meningioma during the reviewed period, 74 (52%) suffered a recurrence, in which the median (interquartile range, IQR) time to recurrence was 14 (IQR 6-34) months. Among those tumors subtotally resected, the median pre- and postoperative tumor volumes were 17.19 cm3 (IQR 7.47-38.43 cm3) and 2.31 cm3 (IQR 0.98-5.16 cm3), which corresponded to a percentage resection of 82% (IQR 68%-93%). Postoperatively, the median growth rate was 0.09 cm3/year (IQR 0-1.39 cm3/year). Factors associated with recurrence in multivariate analysis included preoperative tumor volume (hazard ratio [HR] 1.008,95% confidence interval [CI] 1.002-1.013, p = 0.008), falcine location (HR 2.215, 95% CI 1.179-4.161, p = 0.021), tentorial location (HR 2.410, 95% CI 1.203-4.829, p = 0.024), and African American race (HR 1.811, 95% CI 1.042-3.146, p = 0.044). Residual volume (RV) was associated with high absolute annual growth rate (odds ratio [OR] 1.175, 95% CI 1.078-1.280, p < 0.0001), with the maximum RV benefit at < 5 cm3 (OR 4.056, 95% CI 1.675-9.822, p = 0.002). By identifying predictors of recurrence and growth rate, this study helps identify potential patients with a high chance of recurrence following subtotal resection, which are those with large preoperative tumor volume, falcine location, tentorial location, and African American race. Higher RVs were associated with tumors with higher postoperative growth rates. Recurrences typically occurred 14 months after surgery.

Current Paradigm of Treatment for Pancreatic Neuroendocrine Tumor

Pancreatic neuroendocrine tumor (PNET) refer to tumors originating from the islet of Langerhans and shows various prognosis based on the presence or absence of symptoms due to hormone secretion, the Ki-67 cell proliferation index, and the histologic grade, and according to the degree of disease progression defined by the tumor-node-metastasis (TNM) stage classification. The purpose of medical treatment for PNET is to control symptoms or inhibit tumor growth. Somatostatin analogues can be administered for the purpose of controlling symptoms caused by the secretion of specific hormones, and are accepted as effective drugs for inhibiting the progression of G1/G2 tumors based on World Health Organization (WHO) classification with a Ki-67 cell proliferation index less than 20%. Among the molecularly targeted agents, everolimus and sunitinib can be considered in patients with WHO G1/G2 PNET showing progression after somatostatin analog therapy. Cytotoxic chemotherapy is generally administered to patients with large tumor volume and rapidly progressing metastatic NET, and etoposide/cisplatin combination therapy has been considered as a standard treatment. For the patient group of Grade 3 PNET (well differentiated) newly classified by the WHO 2017 classification, guidelines for standard treatment have not yet been established. As it has been reported, studies are needed to evaluate the treatment response rate of somatostatin analogues or molecularly targeted therapies for the patient with Grade 3 PNET. It is important to consider a multidisciplinary approach with all possible treatment options including medical treatment, radical resection of primary or metastatic lesions, liver-directed therapies, and peptide receptor radionuclide therapy for the patients with PNET.

Palliative Treatment of Locally Advanced Non Metastatic Lung Cancer

Introduction: To determine the proportion and the reasons which lead to palliative treatment in patients initially a candidate for concomitant chemoradiotherapy (CCRT). Methods: A retrospective study including patients followed for locally advanced lung cancer newly diagnosed from April 1, 2016, to 12/31/2017 in the radiotherapy department of the National Oncology Institute who received palliative treatment. Results: We collected 52 patients out of a total of 225 stage III patients (23%) followed by lung cancer candidates for CCRT who had undergone palliative treatment. The mean age in our series was 61.23 years [22 - 81] with 86% male. The majority of patients (71%) had Performance Status (PS) ≤ 2. Histological confirmation was obtained by pathological examination in all our patients. It was an adenocarcinoma (ADK) in 54% of cases; squamous cell carcinoma in 46% of cases. The reasons for palliative treatment were mainly due to dosimetric constraints: large tumor volume 22/52 (42%); the tumor location close to the bone marrow in 15 of 52 (29%) patients; and general Performance Status impairment (29%) in 15 of 52 patients. Palliative treatment consisted of palliative chemotherapy in 37 of 52 patients (71%), among whom 19 (51%) were stable after 2 months of chemotherapy, in palliative dose chest radiotherapy on the pulmonary parenchyma and/or mediastinum in 10 of 52 (19%) patients, and supportive care in 5 (10 %) patients. We observed 40/52 (77%) cases of stationary course, 04/52 (8%) cases of progress to metastases, and 08/52 (15%) deaths before radiotherapy. Conclusion: A large proportion of patients followed for locally advanced non-metastatic lung cancer are not eligible for curative treatment. The reasons for the palliative treatment of patients followed for lung cancer candidates for CCRT are variable but for a large proportion of patients due to the deterioration of their state of health during their diagnostic journey. Hence, there is the need to improve the early diagnosis and early management of patients with lung cancer to avoid delayed care.

MiR-338-5p-ZEB2 axis in Diagnostic, Therapeutic Predictive and Prognostic Value of Gastric Cancer

MiRNAs have been widely reported to be involved in the occurrence and development of cancers. So far, some studies have revealed that miR-338-5p has the functions of tumorigenesis and tumor suppression. However, the role of miR-338-5p in the pathogenesis, progression and treatment of gastric cancer (GC) has not been reported. MiRNAs microarray analysis showed for the first time that miR-338-5p was significantly lower-expression in cisplin-resistant GC cells SGC7901/DDP, and cell viability assay and flow cytometry confirmed that overexpression of miR-338-5p could significantly increase cisplatin-sensitivity of SGC7901/DDP and BGC823 cells. Subsequently, we found that the expression of miR-338-5p in postoperative cancer tissues of GC patients was also significantly lower than the corresponding paracancer tissues. The expression of miR-338-5p in peripheral blood serum of GC patients is generally lower than that of healthy people. Moreover, the low expression of miR-338-5p in the cancer tissues and serum of GC patients was closely associated with larger tumor volume, lymph node metastasis, later stage, and even poorer survival, which was confirmed by close 5-year cases follow-up. ZEB2, as a predictive target of miR-338-5p, its expression was negatively regulated by miR-338-5p and can promote cisplatin-resistance in SGC7901/DDP and BGC823 cells. The expression of ZEB2 in cisplatin-resistant SGC7901/DDP cells and GC tissues were significantly higher than SGC7901 cells and paracancer tissues, respectively. Moreover, the expression of ZEB2 in tumor tissues was negatively correlated with miR-338-5p in tumor tissues and peripheral blood serum of GC patients, and the abnormally high expression of ZEB2 in prospective case studies is positively related with more serious clinical pathology and worse survival. More meaningfully, in a retrospective case study, we found that high ZEB2 expression predicts worse clinical efficacy of platinum chemotherapy. Thus, miR-338-5p-ZEB2 axis have novel diagnostic, therapeutic predictive, and prognostic value in GC patients.

Timing of glioblastoma surgery and patient outcomes: a multicenter cohort study.

BackgroundThe impact of time-to-surgery on clinical outcome for patients with glioblastoma has not been determined. Any delay in treatment is perceived as detrimental, but guidelines do not specify acceptable timings. In this study, we relate the time to glioblastoma surgery with the extent of resection and residual tumor volume, performance change, and survival, and we explore the identification of patients for urgent surgery.MethodsAdults with first-time surgery in 2012–2013 treated by 12 neuro-oncological teams were included in this study. We defined time-to-surgery as the number of days between the diagnostic MR scan and surgery. The relation between time-to-surgery and patient and tumor characteristics was explored in time-to-event analysis and proportional hazard models. Outcome according to time-to-surgery was analyzed by volumetric measurements, changes in performance status, and survival analysis with patient and tumor characteristics as modifiers.ResultsIncluded were 1033 patients of whom 729 had a resection and 304 a biopsy. The overall median time-to-surgery was 13 days. Surgery was within 3 days for 235 (23%) patients, and within a month for 889 (86%). The median volumetric doubling time was 22 days. Lower performance status (hazard ratio [HR] 0.942, 95% confidence interval [CI] 0.893–0.994) and larger tumor volume (HR 1.012, 95% CI 1.010–1.014) were independently associated with a shorter time-to-surgery. Extent of resection, residual tumor volume, postoperative performance change, and overall survival were not associated with time-to-surgery.ConclusionsWith current decision-making for urgent surgery in selected patients with glioblastoma and surgery typically within 1 month, we found equal extent of resection, residual tumor volume, performance status, and survival after longer times-to-surgery.

The clinical features, recurrence risks and surgical strategies of bone invasive pituitary adenomas

ObjectiveBone invasive pituitary adenomas (BIPAs) show obvious malignant behaviour. The aim of this study was to analyse the clinical features, prognosis, recurrence risks and surgical strategies of BIPAs. Patients and methodsClinical charts and radiological information were reviewed retrospectively in 107 consecutive cases of BIPAs. Transnasal endoscopic surgery was adopted with the goal of removing tumours. Scheduled follow-up was performed. ResultsClinical variable analyses revealed a significant correlation between bone invasive range and sex, tumour volume and tumour regrowth. Gross total resection, subtotal resection and partial resection were achieved in 26 cases (24.3 %), 28 cases (26.2 %) and 53 cases (49.5 %), respectively. There was a significant correlation between nongross total resection and female sex, young age, large tumour volume, bone invasive range, tumour regrowth and functional pituitary adenomas in BIPAs. The tumour regrowth rates at 3 years, 5 years and 10 years were 45.3 %, 76.3 % and 97.5 %, respectively. Kaplan-Meier curve analysis showed that tumour volume, bone invasion range, age, recurrent tumours and tumour resection degree were associated with BIPA regrowth. Multivariate analysis showed that tumour resection degree, bone invasive range, and tumour diameter were independent risk factors for BIPA regrowth. ConclusionBIPAs have the characteristics of high surgical risk, low GTR rate and high recurrence rate. There was a significant correlation between bone invasive range and sex, tumour volume and tumour regrowth in BIPAs. Bone invasive range is an independent risk factor for BIPA regrowth.

Correlation of Computed Tomography Parameters with Histology, Stage and Prognosis in Surgically Treated Thymomas.

Background and objectives: The histological classification and staging of thymic tumors remains a matter of debate. The correlation of computed tomography (CT) parameters with tumor histology and stage also still has to be completely assessed. The aim of this study was therefore to analyze the correlation of radiological parameters with histological and staging classifications of thymomas evaluating their prognostic role. Materials and Methods: Data of 50 patients with thymoma submitted to a complete surgical treatment between 2005 and 2015 were retrospectively analyzed. Tumors were classified according to the WHO and Suster and Moran (S&M) histological classifications and to the Masaoka–Koga and tumor, node and metastases (TNM) staging systems. The correlation of CT features with histology and stage and the prognostic role of histopathological and radiological features were assessed. Results: Five-year overall (OS) and disease-free survival (DFS) were 90.3% and 81.1%, respectively. A significant correlation of DFS with the Masaoka–Koga (p = 0.001) and TNM staging systems (p = 0.002) and with the S&M (p = 0.02) and WHO histological classifications (p = 0.04) was observed. CT scan features correlated with tumor stage, histology and prognosis. Moderately differentiated tumors (WHO B3) had a significantly higher incidence of irregular shape and contours (p = 0.002 and p = 0.001, respectively) and pericardial contact (p = 0.036). A larger tumor volume (p = 0.03) and a greater length of pleural contact (p = 0.04) adversely influenced DFS. The presence of pleural (p < 0.001) or lung invasion (p = 0.02) and of pleural effusion (p = 0.004) was associated with a significantly worse OS. Conclusions: Pre-operative CT scan parameters correlate with stage and histology, and have a prognostic role in surgically treated thymomas.

Radiomics Approach for Prediction of Recurrence in Non-Functioning Pituitary Macroadenomas.

ObjectivesA subset of non-functioning pituitary macroadenomas (NFPAs) may exhibit early progression/recurrence (P/R) after surgical resection. The purpose of this study was to apply radiomics in predicting P/R in NFPAs.MethodsOnly patients who had undergone preoperative MRI and postoperative MRI follow-ups for more than 1 year were included in this study. From September 2010 to December 2017, 50 eligible patients diagnosed with pathologically confirmed NFPAs were identified. Preoperative coronal T2WI and contrast-enhanced (CE) T1WI imaging were analyzed by computer algorithms. For each imaging sequence, 32 first-order features and 75 texture features were extracted. Support vector machine (SVM) classifier was utilized to evaluate the importance of extracted parameters, and the most significant three parameters were used to build the prediction model. The SVM score was calculated based on the three selected features.ResultsTwenty-eight patients exhibited P/R (28/50, 56%) after surgery. The median follow-up time was 38 months, and the median time to P/R was 20 months. Visual disturbance, hypopituitarism, extrasellar extension, compression of the third ventricle, large tumor height and volume, failed optic chiasmatic decompression, and high SVM score were more frequently encountered in the P/R group (p < 0.05). In multivariate Cox hazards analysis, symptoms of sex hormones, hypopituitarism, and SVM score were high risk factors for P/R (p < 0.05) with hazard ratios of 10.71, 2.68, and 6.88. The three selected radiomics features were T1 surface-to-volume radio, T1 GLCM-informational measure of correlation, and T2 NGTDM-coarseness. The radiomics predictive model shows 25 true positive, 16 true negative, 6 false positive, and 3 false negative cases, with an accuracy of 82% and AUC of 0.78 in differentiating P/R from non-P/R NFPAs. For SVM score, optimal cut-off value of 0.537 and AUC of 0.87 were obtained for differentiation of P/R. Higher SVM scores were associated with shorter progression-free survival (p < 0.001).ConclusionsOur preliminary results showed that objective and quantitative MR radiomic features can be extracted from NFPAs. Pending more studies and evidence to support the findings, radiomics analysis of preoperative MRI may have the potential to offer valuable information in treatment planning for NFPAs.