Differentiation Of Primary Tumor Research Articles

Impact of pure desmoplastic histological growth patterns in colorectal liver metastasis

BackgroundColorectal cancer (CRC) has increasingly come into worldwide cancer and almost half of patients have liver metastasis (CRLM) during the progression. Therefore, treatment of colorectal cancer liver metastasis (CRLM) is important to improve the prognosis of CRC patients. Histopathological growth patterns (HGPs) of CRLM have emerged as a reliable prognostic marker. In this study, we investigated the role of prognostic impact of pure desmoplastic HGPs (dHGPs), 100% desmoplastic, in CRLM.MethodsThe present study evaluated the HGPs in 71 patients with CRLM who underwent surgery (R0) between 1995 and 2012. HGPs were classified by international consensus guidelines with H&E stained slides. The pure dHGPs was defined as a complete peripheral fibrotic rim around the tumor.ResultsThe dHGP was present in 36.6% (n = 26) and the pure-dHGPs was present in 73% (n = 19) among dHGPs patients. Pure-dHGPs were significantly associated with sex (male), metachronous metastatic period, normal CEA level, shallow tumor invasion and less lymph node metastasis.Patients with dHGPs had longer overall survival (OS) compared to other HGPs (p < 0.05). Furthermore, pure dHGPs patients had longer OS than non-pure dHGPs (90.9% vs. 51.4%, p < 0.05). Multivariate analysis identified pure dHGPs (p = 0.04) and better primary tumor differentiation (p < 0.001) were identified as independent prognostic indicators for OS. Patients with pure dHGPs also had longer disease-free survival (DFS) compared to other HGPs (p < 0.05). Pure-dHGPs patients had longer DFS than non-pure dHGPs (63.4% vs. 28.8%, p < 0.05). Multivariate analysis identified pure dHGPs (p = 0.04) and better primary tumor differentiation (p = 0.03) as independent prognostic indicators.ConclusionsPure desmoplastic HGP might be a good prognostic marker in CRLM.

Colorectal adenocarcinoma with enteroblastic differentiation: a clinicopathological analysis of eight cases

Objective: To investigate the clinicopathological features of colorectal adenocarcinoma with enteroblastic differentiation (CAED). Methods: Eight cases of CAED diagnosed at the Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China from January 2017 to August 2023 were collected. The histopathological, immunohistochemical, molecular and prognostic features of 8 CAED cases were analyzed. The relevant studies were also reviewed. Results: Among the eight patients, there were six males and two females, with an average age of 58 years (range: 29-77 years, median age: 61.5 years). Preoperative serum alpha-fetoprotein levels were elevated in five patients (14.0-286.6 μg/L). Four tumors were located in the colon, and four tumors in the rectum. Two patients were clinically staged as advanced stage (stage Ⅳ), and distant metastasis occurred at the initial diagnosis (one case had liver metastasis, and the other had lung, bone and multiple lymph nodes metastases). Six patients were clinically staged as locally-advanced stage (Stage Ⅱ-Ⅲ). Three of them developed distant metastases after surgery (one case had liver metastasis, one case had lung metastasis, and one case had peritoneal metastasis). Additionally, two patients died at 9 months and 24 months after surgery, respectively. The tumors were composed of various proportions of adenocarcinoma components with enteroblastic differentiation (30%-100%) and classical tubular adenocarcinoma components. The component with enteroblastic differentiation exhibited morphology similar to embryonic intestinal epithelium: cuboidal or columnar tumor cells arranged in tubular, papillary, cribriform, or solid nest patterns, with clear cytoplasm. Immunohistochemical studies showed that tumor cells expressed at least one oncofetal protein (SALL4, Glypican-3, and AFP). In addition, focal squamous differentiation was observed in 3 cases (3/8). Compared to the primary tumor, both CAED and squamous differentiation components were increased in the metastatic tumors. Based on the sequencing results of KRAS, NRAS and BRAF of the primary and/or metastatic tumors, 5 cases were wild-type, while KRAS exon 2 (G13D) mutations were identified in 2 cases. Conclusions: CAED is a rare colorectal malignancy with a dismal prognosis. Accurate pathological diagnosis is prognostically valuable. The histological features of enteroblastic differentiation, elevated serum AFP levels, and the expression of oncofetal proteins play an important role in the tumor diagnosis.

Assessing the effectiveness and safety of surufatinib versus everolimus or sunitinib in advanced neuroendocrine neoplasms: insights from a real-world, retrospective cohort study using propensity score and inverse probability treatment weighting analysis.

While surufatinib, sunitinib, and everolimus have shown efficacy for advanced neuroendocrine neoplasms (NENs) in randomized controlled trials (RCTs), direct comparisons in a real-world setting remain unexplored. This gap highlights the clinical need to understand their comparative effectiveness and safety within the diverse Chinese population. Addressing this, our study provides insights into the real-world performance of these therapies, aiming to inform treatment selection and improve patient outcomes. A retrospective, observational study was conducted at Fudan University Shanghai Cancer Center, including patients with advanced NENs treated with surufatinib, sunitinib, or everolimus between July 2020 and April 2023. Eligibility criteria focused on histologically confirmed, locally advanced, unresectable, or metastatic NENs, with patients having received at least one month of targeted therapy. We employed inverse probability weighting (IPW) with the propensity score (PS) matching to adjust for the bias of baseline characteristics. The assessment of covariates included age, sex, performance status, primary tumor site, functional status, genetic mutations, tumor differentiation, Ki67 index, tumor grade, metastasis site, and previous therapies. The primary outcome was progression-free survival (PFS), and secondary outcomes included objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). The study enrolled 123, 56, and 68 locally advanced or metastatic NEN patients treated with surufatinib, sunitinib, and everolimus, respectively. Before adjusting for confounding factors, surufatinib was used less frequently as a first-line treatment compared to sunitinib and everolimus in pancreatic NENs (pNENs) (11.1% vs. 22.1%, P=0.057). Significant differences were noted in prior treatments and tumor characteristics between surufatinib and everolimus groups in extrapancreatic NENs (epNENs) (P<0.05). Post-IPW, these disparities were resolved (P>0.05). Surufatinib demonstrated superior median PFS (mPFS) in both pancreatic [8.30 vs. 6.33 months, hazard ratio (HR) 0.592, P<0.001] and epNENs (8.73 vs. 3.70 months, HR 0.608, P<0.001) compared to everolimus or sunitinib. Notably, male gender (HR 1.75, P=0.001), functional status (HR 2.09, P=0.01), Ki67 index >20% (HR 12.7, P=0.004), previous somatostatin analogue (SSA) treatment (HR 1.73, P=0.001), germline mutation (HR 5.62, P<0.001), poor differentiation (HR 7.45, P<0.001), liver metastasis (HR 1.72, P=0.001) and multiple treatment lines (HR 1.62 for 2nd line, P=0.04; HR 1.88 for ≥3rd line, P=0.01) were identified as negative prognostic factors for PFS. Conversely, dose adjustment (HR 0.63, P=0.009) and treatment with surufatinib (HR 0.58 for pNEN, P<0.001; HR 0.62 for epNEN, P=0.002) were correlated with longer PFS. In a real-world Chinese cohort, surufatinib significantly outperformed sunitinib and everolimus in prolonging PFS among advanced NEN patients, with identifiable clinical features impacting survival, and conclusions regarding superiority should be interpreted with caution due to the retrospective design. Our findings underscore the need for prospective studies to further validate these results and explore additional predictive biomarkers for personalized treatment strategies.

Second primary squamous cell carcinoma of the oral cavity - a retrospective cohort study of therapeutic procedures and oncological outcome.

In the presented study, the occurrence rates of second primary oral carcinomas and their prognostic relevance were analyzed. All patients with surgically treated oral squamous cell carcinomas within the years 2010 and 2022 in our department were included in this retrospective cohort study. Two groups were designed including patients with second primary carcinomas and patients with local tumor recurrences. Occurrence rates, tumor stages and applied therapies were assessed. Primary outcome was overall survival in dependence of the index tumor. Secondary outcomes were overall survival in dependence of local recurrences or second primary tumors. An overall number of 908 patients was included in the analysis. 98 patients (10.8%) developed a second primary oral squamous cell carcinoma. Patients with second primary tumors presented significantly (p < 0.001) better overall survival in dependence of the index tumor compared to patients suffering from local recurrences. There was no significant difference in overall survival (p = 0.4) in dependence of the date of second primary tumor or local recurrence. Patients with second primary tumors were more likely to receive surgery-based therapy compared to patients with local recurrences who more frequently received definitive radiotherapy. Our data indicates different clinical courses in terms of therapy and survival of patients suffering from second primary tumors compared to patients with local tumor recurrences. This may be due to a more aggressive biology of local recurrences and earlier detection of second primaries due to oncological follow-up of the index tumor. The differentiation of local tumor recurrences and second primary tumors is of clinical relevance, as applicable therapies and resulting prognosis may differ significantly.

Bilateral breast metastasis due to rectal cancer: A rare case report

Metastasis from solid organs to the breast is rare. Similarly, metastasis from the rectum to the breast is a quite rare clinical condition. In particular, metastasis from the rectum to the bilateral breast is much less common. We reported a women patient with bilateral breast metastasis from the rectum at the age of 58 years. Extensive metastatic mass was detected in both breasts on Positron Emission TomographyComputer Tomography and biopsy was performed separately from the masses of both breasts. CDX-2 positive, Cytokeratin 7 negative, estrogen receptors negative, progesterone receptors negative in tumoral areas immunohistochemically verified the breast metastasis of rectal adenocarcinoma. In light of this information, biopsy should be performed to direct the treatment in patients with solid organ cancer with a potential mass in the breast in need of metastasis or primary tumor differentiation.

Head to head comparison of 68Ga-DOTA-FAPI-04 vs 18F-FDG PET/CT in the evaluation of primary extrapulmonary tumors in the chest.

We conducted a prospective study using 18F-flurodeoxyglucose (18F-FDG) and 68Ga-DOTA-FAPI-04 (fibroblast-activation protein inhibitor, 68Ga-FAPI) PET/CT to diagnose, differentiate, and stage primary extrapulmonary tumors of the thorax. Fifty-four participants were undergoing 18F-FDG and 68Ga-FAPI PET/CT and divided into the benign, intermediate, and malignant based on pathology. The maximum standardized uptake value (SUVmax), the tumor-to-blood pool ratio, and tumor-to-liver ratio were compared for primary tumors, lymph nodes, and metastases between the two modalities by two independent samples t tests. One-way ANOVA was used to compare the uptake of 18F-FDG or 68Ga-FAPI among the three groups. Fifty-four participants were confirmed to have 71 primary lesions, 56 metastatic lymph nodes, and 43 metastatic lesions. 18F-FDG PET/CT could both effectively distinguish malignant lesions from non-malignant lesions, accuracies of 87.32% (p < 0.001). 68Ga-FAPI PET/CT effectively differentiated benign lesions from the non-benign, accuracy being 91.55% (p < 0.001). The accuracies of 18F-FDG and 68Ga-FAPI for detecting lymph node metastasis were 77.22% (61/79) and 87.34% (69/79) (p = 0.096). The uptake of 68Ga-FAPI in metastatic lymph nodes was significantly higher than that of the nonmetastatic (p < 0.001). The detection rate of 68Ga-FAPI PET/CT for metastatic lesions was significantly higher than that of 18F-FDG, 100% (43/43) vs. 53.49% (23/43) (p < 0.001). Compared with 18F-FDG PET/CT, 68Ga-FAPI PET/CT changed the treatment strategy of 7.4% (4/54) participants. 68Ga-FAPI PET/CT is valuable in the diagnosis and differentiation of primary extrapulmonary tumors and superior to 18F-FDG PET/CT for evaluating lymph node and distant metastasis. The application of 68Ga-FAPI PET/CT in primary extrapulmonary chest tumors is valuable, which is reflected in diagnosis, differentiation and exploration of lymph node metastasis and distant metastasis. • 68Ga-FAPI PET/CT is valuable in the diagnosis, differentiation, and staging of primary extrapulmonary tumors. • 68Ga-FAPI PET/CT is superior to 18 F-FDG PET/CT for evaluating lymph node and distant metastasis.

MRI-based radiomics nomogram for differentiation of solitary metastasis and solitary primary tumor in the spine

BackgroundDifferentiating between solitary spinal metastasis (SSM) and solitary primary spinal tumor (SPST) is essential for treatment decisions and prognosis. The aim of this study was to develop and validate an MRI-based radiomics nomogram for discriminating SSM from SPST.MethodsOne hundred and thirty-five patients with solitary spinal tumors were retrospectively studied and the data set was divided into two groups: a training set (n = 98) and a validation set (n = 37). Demographics and MRI characteristic features were evaluated to build a clinical factors model. Radiomics features were extracted from sagittal T1-weighted and fat-saturated T2-weighted images, and a radiomics signature model was constructed. A radiomics nomogram was established by combining radiomics features and significant clinical factors. The diagnostic performance of the three models was evaluated using receiver operator characteristic (ROC) curves on the training and validation sets. The Hosmer–Lemeshow test was performed to assess the calibration capability of radiomics nomogram, and we used decision curve analysis (DCA) to estimate the clinical usefulness.ResultsThe age, signal, and boundaries were used to construct the clinical factors model. Twenty-six features from MR images were used to build the radiomics signature. The radiomics nomogram achieved good performance for differentiating SSM from SPST with an area under the curve (AUC) of 0.980 in the training set and an AUC of 0.924 in the validation set. The Hosmer–Lemeshow test and decision curve analysis demonstrated the radiomics nomogram outperformed the clinical factors model.ConclusionsA radiomics nomogram as a noninvasive diagnostic method, which combines radiomics features and clinical factors, is helpful in distinguishing between SSM and SPST.

Efficacy of Immune Checkpoint Inhibitors against Advanced or Metastatic Neuroendocrine Neoplasms: A Systematic Review and Meta-Analysis.

Simple SummaryNeuroendocrine neoplasms (NENs) are relatively rare neoplasms, but their incidence is rising. Despite the recent understanding of and advances in the treatment of NENs, the clinical outcomes of patients with NENs, especially high-grade NENs, are poor. This meta-analysis was conducted to systematically evaluate the effectiveness of immune checkpoint inhibitors (ICIs) in patients with advanced or metastatic NENs. In 10 studies with 464 patients, the pooled overall response rate was 15.5% (95% confidence interval, 9.5–24.3%), but the response differed according to the primary tumor site, tumor differentiation, and drug regimen. Poorly differentiated NENs consistently showed a better overall response rate than well-differentiated NENs in multiple sensitivity analyses, suggesting that different expression of immune checkpoints and tumor mutational burden may influence the treatment efficacy of ICIs for advanced or metastatic NENs. The variation in treatment efficacy of ICIs according to tumor differentiation and drug regimen should be considered for patient-tailored management.We performed a systematic review and meta-analysis of the treatment efficacy of immune checkpoint inhibitors (ICIs) in advanced/metastatic neuroendocrine neoplasms (NENs). MEDLINE and EMBASE were searched to identify studies that provide data on treatment response and/or survival outcomes of advanced/metastatic NEN patients treated with ICIs. The overall response rate (ORR) was pooled using a random-effects model. Meta-regression was performed to explore factors influencing the ORR. Individual patient data (IPD) meta-analysis of survival was performed using stratified Cox regression. Ten studies (464 patients) were included. The overall pooled ORR was 15.5% (95% confidence interval (CI), 9.5–24.3%), and it varied according to the primary site (thoracic, 24.7%; gastro–entero–pancreatic, 9.5%), tumor differentiation (poorly differentiated, 22.7%; well-differentiated, 10.4%), and drug regimen (combination, 25.3%; monotherapy, 10.1%). All these variables significantly influenced the ORR. Tumor differentiation was associated with both overall survival and progression-free survival (hazard ratio of poorly differentiated tumors, 4.2 (95% CI, 2.0–8.7) and 2.6 (95% CI, 1.6–4.4), respectively). Thus, the treatment efficacy of ICIs for advanced/metastatic NENs varied according to primary site, tumor differentiation, and drug regimen. Poorly differentiated NENs showed a better ORR than well-differentiated NENs but had a negative impact on survival.

PARP5B is required for nonhomologous end joining during tumorigenesis in vivo.

Poly(ADP-ribose) polymerases (PARP) act as DNA damage sensors that produce poly(ADP-ribose) (PAR) chains at double-strand breaks, facilitating the recruitment of repair factors. Cancers with homologous recombination defects are sensitive to small molecule PARP inhibitors. Despite PARP5B gene copy number changes in many cancers, the effects of this genetic alteration on tumor phenotype are largely unknown. To better understand this clinical finding, we characterized a PARP5B null mutation in a carcinogen-induced in vivo head and neck squamous cell carcinoma (SCC) model. Reduced PARP5B expression inhibited tumor growth, induced primary tumor differentiation and apoptosis, and inhibited cell proliferation and metastasis. Loss of PARP5B expression-induced ataxia telangiectasia and Rad3 related (ATR) activation and depleted the cancer stem cell fraction. PARP5B null tumor cells lacked 53BP1+double-strand break foci, ATM activation, and p53 induction compared to PARP5B+/+cancers. PARP5B null SCC expresses a multiprotein complex containing PML, pRPA, Rad50, Rad51, XRCC1, proliferating cell nuclear antigen (PCNA), and Mcm2, suggesting an HR-mediated repair mechanism at DNA replication foci. Low doses of etoposide combined with the PARP5B inhibitor XAV939 induced senescence and apoptosis in human SCC lines. NBS1 overexpression in these cells inhibited the effects of low-dose etoposide/XAV939 treatment. Our results indicate that PARP5B inhibition is new targeted cancer therapy.

Clinicopathological analysis of lung metastatic tumor

Objective: To investigate the clinicopathological features and differential diagnosis of metastatic tumors in the lung. Methods: The clinicopathological data of 226 metastatic tumors in the lung were collected at Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, from January 2014 to December 2018, and the pathomorphological characteristics were analyzed. Results: There were 84 males and 142 females, with an age range from 13 to 77 years. There were 122 patients with multiple pulmonary nodules and 104 patients with solitary pulmonary nodule. The tumors of the highest frequencies were colorectal cancer (n=59), followed by trophoblast tumor (n=44), kidney cancer (n=31), breast cancer (n=20), cervix cancer (n=14), and urinary urothelium cancer (n=8). The time from the diagnosis of primary tumors to metastasis and the status of surgical treatment varied by tumor origin. The morphology of metastatic lung tumors overlapped with that of the primary tumors to some extent. The relative specific morphological characteristics and the presence of carcinoma in situ surrounding the tumors should be carefully searched for to confirm the tumor origin. The metastatic tumors of the lung had morphological characteristics, immunohistochemical TTF1 (-) and tumor of various sources, while the primary tumor differentiation had relatively specific antibodies: colorectal cancer CK20 (+), CDX2 (+), CK7 (-); malignant trophoblastic tumor, HCG (+); renal clear cell carcinoma CD10 (+), vimentin (+), CK7 (-); breast cancer, GATA3 and ER (+); cervical cancer, p16 (+); urothelial carcinoma, CK20, p63 and GATA3 (+). Conclusions: There is overlap between pulmonary metastatic tumor and primary tumor in morphology. Therefore, the diagnosis should be made by combining clinical history, pathological morphology and immunophenotypic characteristics.

A CLINICO-PATHOLOGICAL STUDY OF CARCINOMA BREAST WITH SPECIAL REFERENCE TO SERUM CEA LEVELS & ITS RELATIONSHIP WITH TREATMENT

BACKGROUND: Carcinoembryonic antigen (CEA) is used as a tumor marker for breast cancer (BC) &amp; follow up of patients pre- or post- chemotherapy. In order to better dene clinical usefulness of CEA in breast cancer patients (BCP) we determined its baseline pre-treatment levels and correlated them with main parameters of primary tumor and metastases.PATIENTS AND METHODS: The main experimental group consisted of 53 females with histologically conrmed diagnosis of BC. The obtained results have been compared with those of three follow-up groups: pre-operative, immediate post-operative and 2nd follow up Post operative patients with other types and locations of cancer. In both cancer groups the parameters of primary tumor (size, grade) and metastases (time interval to metastases, location, size) have been determined. Circulating levels of CEA were measured by the means of sandwich ELISA assay. Results were processed by means of t-test, two way analysis of variance in p value. RESULTS: Baseline levels of CEA in BCP were signicantly higher than in healthy women (p &lt; 0.0001), and in patients with other types and locations of cancer (p &lt; 0.007). There also was signicant difference (p &lt; 0.001) between serum CEA in other cancer patients and healthy women. Baseline CEA levels were in signicant positive correlation with the size of primary tumor both in all BCP (p &lt; 0.03) and in hyperCEA BCP (p &lt; 0.002), while in other cancer patients such a correlation did not exist. There was no correlation between CEA and degree of differentiation of primary tumor either in BCP or in other cancer patients. The average circulating levels of CEA in metastatic BCP were signicantly higher (p &lt; 0.03) in comparison to non-metastatic patients, while in other cancer patients such a difference did not show up. There was signicant correlation (p &lt; 0.0001) between circulating CEA and the size of metastases in all BCP and in subgroup of hyperCEA BCP, while in other cancer patients it was not a case. There was no correlation between serum CEA and other two metastatic parameters either in BCP or in other cancer patients. CEA does not have high tumor specicity for BC CONCLUSIONS: 1 since its baseline levels may be elevated in other types of cancer . Circulating levels of CEA in BCP are directly dependable on the size of both primary and metastatic tumor. CEA is a tumor antigen of less differentiated cancer cells. Circulating CEA is a good prognostic marker for patients with metastatic BC.

Role of 18F-FDG PET/CT in the differential diagnosis of primary benign and malignant unilateral adrenal tumors.

This retrospective study was performed to estimate the clinical role of whole-body positron emission tomography/computed tomography (PET/CT) using 2-[18F] fluoro-2-deoxy-D-glucose (FDG) in the differential diagnosis of primary benign and malignant unilateral adrenal tumors. A total of 64 patients (31 male, 33 female; age range: 3-76 years, mean: 48.5) with a confirmed unilateral adrenal tumor underwent 18F-FDG PET/CT examination for diagnosis and staging. The whole-body 18F-FDG PET/CT examination excluded metastasis, and all patients were confirmed by operation and biopsy pathology. Their clinical data and pathological results were collected. On visual analysis of PET/CT imaging, adrenal uptake was based on a three-scale grading system. The region of interest (ROI) was delineated in the liver and the renal lesion site. Standardized uptake value (SUV) measurements were determined on a standardized reconstruction, and the maximum values (SUVmax) of the lesion and liver were measured. The ratio of tumor to the liver was defined as T/L. Visual interpretation, SUVmax-receiver operating characteristics (ROC) method, and T/L-ROC method were used to analyze the diagnostic accuracy. A total of 64 lesions (48 benign, 16 malignant lesions) were detected. The visual analysis found that 100% of Grade I cases were benign, 90.9% of Grade II cases were benign, and 65.1% of Grade III cases were benign. The SUVmax of malignant lesions (10.0±5.8) was higher than that of benign lesions (5.4±5.3, P<0.05). The T/L was 3.39±1.79 for malignant lesions and 1.99±2.09 for benign lesions (P<0.05). In the differentiation of primary benign and malignant unilateral adrenal tumors, the sensitivity, specificity, and accuracy of the SUVmax-ROC method (cut-off value =5.65) were 81.25%, 72.91%, 75.00%, and the positive and negative predictive values were 50.00% and 92.11%, respectively. The sensitivity, specificity, and accuracy of the T/L-ROC method (cut-off value =1.52) were 93.73%, 62.50%, 70.31%, and the positive and negative predictive values were 46.88% and 96.77%, respectively. 18F-FDG PET/CT improved diagnostic accuracy in differentiating primary benign and malignant unilateral adrenal tumors. There was a high negative predictive value, and for positive prediction, other tracer imaging is needed for differential diagnosis.

Predicting Histology of Tracheobronchial Neoplasms: A CT Based Differentiation Model

Tracheobronchial (TB) tumors follow same pathological classification as lung neoplasms; however, some entities are known to favor airways. Distinction of pathological types is necessary for suggesting appropriate management strategy. To evaluate utility of multidetector CT (MDCT) in differentiation of primary TB tumors; and assess validity of a scoring system based on imaging biomarkers to differentiate tumor types. MDCT features of 45 patients were analyzed for location, shape, calcification, attenuation, parenchymal changes, bronchoceles, extraluminal extension, lymphadenopathy, metastases. The two largest groups were compared with each other and remaining entities using Chi square tests. Six-point scoring system combining the differentiating features was devised and receiver operating characteristic curve analysis performed. The most frequent type was neuroendocrine tumors (NET) (51.1%), followed by salivary gland tumors (SGT) (20%); including adenoid cystic carcinoma (ACC) (13.3%) and mucoepidermoid carcinoma (MEC) (6.7%). Comparing NETs with other entities as a whole, and independently with SGTs, significant difference was found among location (p = 0.05 and 0.001 respectively), shape (p < 0.001), calcification (p = 0.038 and 0.041 respectively), attenuation (p = 0.001 and 0.019 respectively), bronchoceles (p = 0.013 and 0.010 respectively). Significant difference was found among ACC and MEC in location (p = 0.01) and morphology (p < 0.001). On receiver operating characteristic (ROC) curve analysis of the score, areas under curve for NET, SGT and ACC were 0.913, 0.872 and 0.962 respectively. Suggested cut-off values were >3.5 for carcinoid (sensitivity 70%, specificity 91%), <2.5 for SGT (sensitivity 78%, specificity 75%), <1.5 for ACC (sensitivity 83%, specificity 92%). Use of a scoring system enables maximum diagnostic accuracy in MDCT differentiation of TB tumors.

Significance of postoperative adjuvant chemotherapy with an oxaliplatin-based regimen after simultaneous curative resection for colorectal cancer and synchronous colorectal liver metastasis: a propensity score matching analysis

BackgroundExpansion of the indication for liver resection and new regimens for systemic chemotherapy have improved postoperative outcomes for synchronous colorectal liver metastases (CRLM). However, such cases can still have a high recurrence rate, even after curative resection. Therefore, there is a need for postoperative adjuvant chemotherapy (POAC) after liver resection in patients with CRLM. There are few studies of the efficacy of POAC with an oxaliplatin-based regimen after simultaneous resection for colorectal cancer and CRLM with curative intent. The goal of the study was to compare POAC with oxaliplatin-based and fluoropyrimidine regimens using propensity score (PS) matching analysis.MethodsThe subjects were 94 patients who received POAC after simultaneous resection for colorectal cancer and synchronous CRLM, and were enrolled retrospectively. The patients were placed in a L-OHP (+) group (POAC with an oxaliplatin-based regimen, n = 47) and a L-OHP (−) group (POAC with a fluoropyrimidine regimen, n = 47). Recurrence-free (RFS), cancer-specific (CSS), unresectable recurrence-free (URRFS), remnant liver recurrence-free (RLRFS), and extrahepatic recurrence-free (EHRFS) survival were analyzed.ResultsBefore PS matching, the L-OHP (+) and (−) groups had no significant differences in RFS, CSS, URRFS, RLRFS, and EHRFS. Univariate analysis indicated significant differences in age, preoperative serum CEA (≤ 30.0 ng/mL/ > 30.0 ng/mL), differentiation of primary tumor (differentiated/undifferentiated), T classification (T1–3/T4), number of hepatic lesions and maximum diameter of the hepatic lesion between the L-OHP (+) and (−) groups. After PS matching using these confounders, RFS was significantly better among patients in the L-OHP (+) group compared with the L-OHP (−) group (HR 0.40, 95% CI 0.17–0.96, p = 0.04). In addition, there was a trend towards better RLRFS among patients in the L-OHP (+) group compared with the L-OHP (−) group (HR 0.42, 95% CI 0.17–1.02, p = 0.055). However, there were no significant differences in CSS, URRFS and EHRFS between the L-OHP (+) and (−) groups.ConclusionsPS matching analysis demonstrated the efficacy of POAC with an oxaliplatin-based regimen in RFS and RLRFS.

Amide proton transfer weighted (APTw) imaging based radiomics allows for the differentiation of gliomas from metastases

We sought to evaluate the utility of radiomics for Amide Proton Transfer weighted (APTw) imaging by assessing its value in differentiating brain metastases from high- and low grade glial brain tumors. We retrospectively identified 48 treatment-naïve patients (10 WHO grade 2, 1 WHO grade 3, 10 WHO grade 4 primary glial brain tumors and 27 metastases) with either primary glial brain tumors or metastases who had undergone APTw MR imaging. After image analysis with radiomics feature extraction and post-processing, machine learning algorithms (multilayer perceptron machine learning algorithm; random forest classifier) with stratified tenfold cross validation were trained on features and were used to differentiate the brain neoplasms. The multilayer perceptron achieved an AUC of 0.836 (receiver operating characteristic curve) in differentiating primary glial brain tumors from metastases. The random forest classifier achieved an AUC of 0.868 in differentiating WHO grade 4 from WHO grade 2/3 primary glial brain tumors. For the differentiation of WHO grade 4 tumors from grade 2/3 tumors and metastases an average AUC of 0.797 was achieved. Our results indicate that the use of radiomics for APTw imaging is feasible and the differentiation of primary glial brain tumors from metastases is achievable with a high degree of accuracy.

Discordance between central versus local response assessments in neuroendocrine tumor (NET) patients (pts) enrolled in A021202.

361 Background: Assessment of tumor response in extrapancreatic NETs with metastases can be very challenging. Previous studies suggest a high degree of discordance between local and central imaging reviews, which has implications for clinical practice and trial design. Methods: Serial images archived from a randomized phase II trial (A021202) of pazopanib vs placebo in progressive non-pancreatic NETs were evaluated by central review, with real-time review conducted at the time of locally interpreted progressive disease (PD). The primary endpoint of the trial was progression-free survival (PFS) by central review. Discordances between central (Alliance Imaging Core Laboratory) and local (investigator-reported) reviews were assessed. Scan-level and pt-level results across both treatment arms were evaluated. Kappa tests were used to test concordance based on source of review. Results: 151 pts had a total of 724 scans with response adjudication by both local and central RECIST review. Discordance was observed in both directions. Overall, 20% of scans (143/724) had discordant classifications. The most common discordances were: stable disease (SD) on local vs. PD on central review (82/143=57%), and PD on local vs. SD on central review (32/143=22%). On a pt level, 78 of 151 pts (52%) had discordant reviews; 8 had &gt;1 type of discordance. Overall, 30% of pts (N=45) had a determination of PD on central review, but SD or better on local review, potentially resulting in excessive exposure to therapy. In contrast, 20% (N=30) were classified as PD on local read but SD or better on real-time central review (which did not necessarily translate into an abbreviated course of treatment). Cohen’s kappa statistics revealed only moderate concordance between local and central reviewers both at the scan (K=0.48, 95% CI: 0.42 – 0.55) and pt (K=0.41, 95% CI: 0.32 – 0.5) levels, with no significant influence by treatment arm, primary tumor site, tumor functionality, histology, differentiation or primary disease spread. Conclusions: Discordance was observed in both directions, where 30% of pts were potentially kept on study drug too long (based on central read), and 20% would have been taken off study treatment early for local PD were it not for real-time central review. Although this bidirectional discordance did not affect the overall findings of the PFS outcome between arms in the trial, these analyses highlight the high prevalence of discordance, the potential to negatively influence treatment duration in both directions, and the need for more straightforward methods of assessing treatment response in carcinoid. Support: U10CA180821, U10CA180882, U24CA196171; NETRF Investigator Award; https://acknowledgments.alliancefound.org Clinical trial information: NCT01841736.

Extrapolating Prognostic Factors of Primary Curative Resection to Postresection Recurrences Hepatocellular Carcinoma Treatable by Radiofrequency Ablation.

Objective Recurrence after curative resection for hepatocellular carcinoma (HCC) is a major cause of death from this disease. Factors of primary curative resection are available and potential in the prognosis of follow-up treatment. Our aim was to assess the prognostic significance of primary curative resection factors in recurrent HCC patients undergoing radiofrequency ablation therapy (RFA). Methods In this retrospective study, we assessed 235 patients who underwent limited RFA of HCC recurrences (tumors ≤ 5 cm; nodules ≤ 3) after primary curative resection. Factors of primary curative resection were collected, and overall survival and recurrence-free survival were evaluated by the Kaplan-Meier method. Univariate and multivariate analyses were used to identify significant prognostic factors. Results After a median follow-up of 36 months, 54 patients died, and 128 patients had hepatic recurrence. On univariate analyses, patients whose primary tumors were less differentiated (p = 0.032 and p = 0.048) and required less time to recur (p = 0.013 and p = 0.001) after curative resection displayed poorer overall survival and higher recurrence rates following RFA. On multivariate analyses, the pathologic tumor grade (p = 0.026 and p = 0.038) and recurrence-free survival after primary curative resection (p = 0.028 and p < 0.001) emerged as independent risk factors of survival and HCC recurrence. Conclusions Primary tumor differentiation and time to recurrence after curative resection are viable prognostic factors of overall survival and further recurrence risk in patients undergoing RFA of recurrent HCC.

Acetylcholinesterase and human cancers.

The enzyme acetylcholinesterase (AChE) is a serine hydrolase whose primary function is to degrade acetylcholine (ACh) and terminate neurotransmission. Apart from its role in synaptic transmission, AChE has several "non-classical" functions in non-neuronal cells. AChE is involved in cellular growth, apoptosis, drug resistance pathways, response to stress signals and inflammation. The observation that the functional activity of AChE is altered in human tumors (relative to adjacent matched normal tissue) has raised several intriguing questions about its role in the pathophysiology of human cancers. Published reports show that AChE is a vital regulator of oncogenic signaling pathways involving proliferation, differentiation, cell-cell adhesion, migration, invasion and metastasis of primary tumors. The objective of this book chapter is to provide a comprehensive overview of the contributions of the AChE-signaling pathway in the growth of progression of human cancers. The AChE isoforms, AChE-T, AChE-R and AChE-S are robustly expressed in human cancer cell lines as well in human tumors (isolated from patients). Traditionally, AChE-modulators have been used in the clinic for treatment of neurodegenerative disorders. Emerging studies reveal that these drugs could be repurposed for the treatment of human cancers. The discovery of potent, selective AChE ligands will provide new knowledge about AChE-regulatory pathways in human cancers and foster the hope of novel therapies for this disease.

Cervical lymph node metastasis in squamous cell carcinoma of the buccal mucosa: a retrospective study on pattern of involvement and clinical analysis.

Background The study was performed with an aim to map the pattern of metastasis of squamous cell carcinomas of buccal mucosa to various cervical lymph node levels and analyze its correlation with primary tumor size and histo-pathological grading. Material and Methods 254 patients with squamous cell carcinoma of the buccal mucosa treated with surgery first approach were analyzed retrospectively. The tumor size was noted from pre-operative CT Scans and were divided into early and advanced tumors. The resected specimen was studied to note the histo-pathological grading of the squamous cell carcinoma and the metastatic deposits at various lymph node levels. Results Out of 254 patients (149 females, 105 males), 145 patients showed histo-pathologically proven metastatic deposits in one or more lymph nodes out of which there were 56 patients showing occult metastasis. 78/145 patients showed metastatic involvement of level IB and/or IA lymph nodes, 31 showed involvement of level II and/or I lymph nodes, 27 showed involvement of level III with or without involvement of level I and II and 9 showed metastasis to level IV and V lymph nodes with or without level I, II or III lymph nodes. Cervical lymph node metastasis had statistically significant association with tumor size with advanced tumors showing worse pattern of metastatic spread beyond level I and II lymph nodes. As the degree of differentiation of squamous cell carcinoma reduced, they were more prone for cervical metastasis with moderately and poorly differentiated squamous cell carcinoma showing higher involvement of level III, IV and V lymph nodes. Conclusions The majority of buccal mucosa cases showed metastasis to level I, II and III lymph nodes out of which level IB and/or IA was most frequently involved. Metastasis to level IV and V lymph nodes was rare and was seen especially in patients with advanced primary tumor and poor histo-pathologic differentiation. Key words:Oral squamous cell carcinoma (OSCC), cervical lymph node metastasis, histologic differentiation, locally advanced disease.

Prognostic factors and therapeutic effects of different treatment modalities for colorectal cancer liver metastases.

BACKGROUNDColorectal cancer (CRC) is one of the most common malignant tumors in China, and the liver is the most common metastatic site in patients with advanced CRC. Hepatectomy is the gold standard treatment for colorectal liver metastases. For patients who cannot undergo radical resection of liver metastases for various reasons, ablation therapy, interventional therapy, and systemic chemotherapy can be used to improve their quality of life and prolong their survival time.AIMTo explore the prognostic factors and treatments of liver metastases of CRC.METHODSA retrospective analysis was conducted on 87 patients with liver metastases from CRC treated at the Liaoning Cancer Hospital and Institute between January 2005 and March 2011. According to different treatments, the patients were divided into the following four groups: Surgical resection group (36 patients); ablation group (23 patients); intervention group (15 patients); and drug group (13 patients). The clinicopathological data and postoperative survival of the four groups were analyzed. The Kaplan-Meier method was used for survival analysis, and the Cox proportional hazards regression model was used for multivariate analysis.RESULTSThe median survival time of the 87 patients was 38.747 ± 3.062 mo, and the 1- and 3-year survival rates were 87.5% and 53.1%, respectively. The Cox proportional hazards model showed that the following factors were independent factors affecting prognosis: The degree of tumor differentiation, the number of metastases, the size of metastases, and whether the metastases are close to great vessels. The results of treatment factor analysis showed that the effect of surgical treatment was better than that of drugs, intervention, or ablation alone, and the median survival time was 48.83 ± 4.36 mo. The drug group had the worst prognosis, with a median survival time of only 13.5 ± 0.7 mo (P < 0.05). For patients with liver metastases of CRC near the great vessels, the median survival time (27.3 mo) of patients undergoing surgical resection was better than that of patients using other treatments (20.6 mo) (P < 0.05).CONCLUSIONPatients with a low degree of primary tumor differentiation, multiple liver metastases (number of tumors > 4), and maximum diameter of liver metastases > 5 cm have a poor prognosis. Among drug therapy, intervention, ablation, and surgical treatment options, surgical treatment is the first choice for liver metastases. When liver metastases are close to great vessels, surgical treatment is significantly better than drug therapy, intervention, and ablation alone.