Original Tumor Site Research Articles

HRD and other targetable mutations in ovarian cancer: The importance of tumor site of origin and cell type

HRD and other targetable mutations in ovarian cancer: The importance of tumor site of origin and cell type

Endoscopic surgery for squamous cell carcinoma in the nasal cavity and ethmoid sinus: A retrospective observational study

ObjectiveReports of endoscopic surgery for squamous cell carcinoma of the nasal cavity and ethmoid sinus are limited. Herein, we present a comprehensive account of the results obtained from performing endoscopic surgery based on the concept of en bloc resection. MethodsThis was a retrospective observational study of patients who underwent nasal endoscopic surgery for squamous cell carcinoma of the nasal cavity and ethmoid sinus at a hospital between July 2018 and December 2021. Primary endpoints were overall survival, relapse-free survival, and local recurrence-free survival. Data on tumor stage, tumor site of origin, postoperative treatment, and papilloma-related status were reviewed. Statistical analyses included the Kaplan–Meier method, Cox regression analysis, and Fisher's exact test. ResultsTwenty-two patients with a median age of 62 (range 27–84) years, comprising 15 male and 7 female, were included in this study, and the median duration of observation was 2.1 (range 0.6–4.3) years. The 2-year overall survival, relapse-free survival, and recurrence-free survival rates were 91.0%, 69.9%, and 79.0%, respectively. Cancer of the nasal cavity was significantly superior to that of the ethmoid sinus in terms of local recurrence-free survival (p = 0.03). The patients who underwent postoperative treatment had significantly worse recurrence-free survival rates than those who did not receive postoperative treatment (p = 0.03). ConclusionsThis study examined the results of the endoscopic treatment for squamous cell carcinoma of the nasal cavity and ethmoid sinus with the concept of en bloc resection. Patients with ethmoid sinus carcinoma had a greater risk for local recurrence, and the prognosis for patients requiring postoperative treatment was poor.

Analysis of the different pathways of ectopic recurrence of craniopharyngioma in pediatric patients: presentation of cases and review of the literature.

Craniopharyngioma is a tumor derived from the squamous epithelium of Rathke's pouch. Despite successful excision, recurrence is common, typically occurring at the original tumor site. More rarely, recurrences can manifest at distant locations. This article reports on three distinct types of ectopic recurrence and reviews the existing literature. We reviewed clinical records and neuroimaging data of craniopharyngioma patients at our institution, identifying three cases of ectopic recurrence. Additionally, we conducted a literature review of similar cases published between 1975 and 2023, focusing on historical background, pathophysiology, clinical and radiological features, and treatment options. We identified nineteen articles detailing ectopic recurrence of craniopharyngiomas in pediatric patients. The right frontal lobe was the most frequently reported site of recurrence. The shortest interval to recurrence was 11months, while the longest was 14years. Most cases were managed with surgical resection, yielding positive outcomes. In our cases, the recurrence sites were temporal intraparenchymal, intraosseous orbital, and occipital intraventricular. All were successfully treated with surgery, with no subsequent recurrences. Although craniopharyngiomas are histologically benign, they can recur locally and, more rarely, at distant sites. Surgical intervention is generally well-tolerated. Further research into tumor cell dissemination mechanisms is essential to develop strategies for preventing ectopic recurrence.

Retrospective study on the profile of patients undergoing intraoperative radiotherapy with INTRABEAM for breast cancer treatment at a Brazilian cancer center.

e12538 Background: Conservative breast therapy combined with adjuvant radiotherapy has been the preferred treatment for early-stage breast cancer for many decades. Considering that most breast cancer recurrences occur near the original tumor site, partial breast radiotherapy has become an alternative for patients in this scenario, allowing for a single-dose radiation application directly to the tumor site. This technique has advantages such as reducing local toxicity and improving the quality of life for treated patients, in addition to decreasing the waiting time for radiotherapy treatment in developing countries like ours. Our case series is the largest in Latin America to date, and we believe that reporting the results of our experience will be valuable for the scientific community and aid in treatment decision-making in low- and middle-income countries. Methods: This is a retrospective study based on data from the medical records of 209 patients with early-stage breast cancer undergoing conservative surgery and intraoperative radiotherapy at A.C. Camargo Cancer Center (São Paulo, Brazil) from 2016 to 2023. Results: In our cohort, 88.5% of tumors were invasive ductal carcinomas. The majority were T1b (41.8%), had histological grade 2 (45.4%), nuclear grade 2 (62.7%), and showed no axillary involvement (87.6%). All patients received intraoperative radiotherapy in a single dose of 20 Gy radiation at the tumor site with a voltage of 50 kV. In our study, 17.7% of patients required additional external radiotherapy due to postoperative histopathological findings inconsistent with treatment indication criteria, including 35.3% for micrometastasis and 32.4% for nodal macrometastasis, 10.8% for narrow or compromised margins, 10.8% for histological types not covered in the final report, 2.7% for multifocality, 2.7% for extensive ductal carcinoma in situ, 2.7% for negative progesterone receptor, and 2.7% for the presence of lymphatic vascular invasion. The average follow-up time for patients was 36 months. The local recurrence rate was 0.5%. Conclusions: The results of this study support established data indicating the efficacy of intraoperative radiotherapy in early-stage breast cancer treatment. Therefore, for carefully selected patients, this technique with should be considered as a treatment option. We will continue to follow this patient cohort to identify the occurrence of late recurrences and publish long-term follow-up data.

Utility of liquid biopsy for predicting cancer type and informing treatment of carcinoma with unknown primary.

e13606 Background: The advent of next-generation sequencing has greatly facilitated physicians in recommending tailored treatments for cancer patients. Despite these advancements, the dependence on the primary tumor site remains crucial for accurate diagnoses, posing a substantial obstacle in cases of carcinomas of unknown primary (CUPs) and hindering optimal patient care. To address this challenge, we propose the implementation of a machine learning model capable of identifying the tissue of origin (TOO) across 16 cancer types. Current standards gravitate to the use of tumor tissue for identifying primary tumor site. Leveraging the advantages of cell-free DNA (cfDNA), our approach provides a non-invasive and highly sensitive alternative to traditional biopsy or radiography methods. Methods: Cell-free DNA was extracted from patients diagnosed with carcinoma of known origin. The model underwent training using a dataset comprising 2,793 cfDNA samples, while the validation set consisted of 1,863 samples. The training and validation cohorts exhibited comparable demographics in terms of sex, age, and cancer types. Employing low-coverage whole genome sequencing (WGS), samples were analyzed to capture cfDNA features, including DNA fragment size distribution, copy number variation, nucleosome coverage pattern, mutational signature, and hotspot regions associated with cancer-related mutations. The final prediction model's accuracy was evaluated based on top 1 and top 2 predictions in accordance with the true tumor site of origin. Results: Overall accuracy of TOO predictions in the training cohort is 80.20% (2240/2793) for top 1 site and 90.26% (2521/2793) for top 2 sites. Overall accuracy of TOO predictions in the validation cohort is 81.80% (1524/1863) for top 1 site and 90.07% (1678/1863) for top 2 sites. Accuracy of tumor site prediction in the validation cohort is highest for lung cancer (Top 1 = 95.9%; Top 2 = 98.0%) tumor sites and lowest for biliary system and kidney tumor types (Top 1 = 54.3% & 57.4%; Top 2 = 71.6% & 63.2%). In the clinical setting, TOO estimation of 12/16 patients with CUP were identified to be in concordance with majority pathological consensus. Of note, two patients with CUP were diagnosed as lung cancer patients through TOO estimation. Molecular biomarkers of lung adenocarcinoma were also identified through targeted sequencing which corroborated the diagnosis, and chemoradiotherapy was recommended to the patient. Conclusions: We developed an accurate predictor of TOO by leveraging machine learning algorithm and incorporating cfDNA mutational, fragmentomic, and epigenetic features. Our results demonstrate high concordance between model-predicted and actual tumor sites across all examined cancer types. This model shows promise in offering valuable insights for the identification of cancers with an unknown primary origin using non-invasive cell free DNA samples.

Identifying somatic fingerprints of cancers defined by germline and environmental risk factors.

Numerous studies over the past generation have identified germline variants that increase specific cancer risks. Simultaneously, a revolution in sequencing technology has permitted high-throughput annotations of somatic genomes characterizing individual tumors. However, examining the relationship between germline variants and somatic alteration patterns is hugely challenged by the large numbers of variants in a typical tumor, the rarity of most individual variants, and the heterogeneity of tumor somatic fingerprints. In this article, we propose statistical methodology that frames the investigation of germline-somatic relationships in an interpretable manner. The method uses meta-features embodying biological contexts of individual somatic alterations to implicitly group rare mutations. Our team has used this technique previously through a multilevel regression model to diagnose with high accuracy tumor site of origin. Herein, we further leverage topic models from computational linguistics to achieve interpretable lower-dimensional embeddings of the meta-features. We demonstrate how the method can identify distinctive somatic profiles linked to specific germline variants or environmental risk factors. We illustrate the method using The Cancer Genome Atlas whole-exome sequencing data to characterize somatic tumor fingerprints in breast cancer patients with germline BRCA1/2 mutations and in head and neck cancer patients exposed to human papillomavirus.

Abstract 6778: New microplate platform with cryopreserved 3D tumor spheroids for faster and convenient pre-clinical testing

Abstract Drug discovery and safety testing depend on predictive in vitro models, including multicellular tissues with organotypic functions. While traditional 2D tumor cell cultures have been extensively used in early drug screening due to their user-friendly nature, automation compatibility, and high throughput, they fall short in representing the intricate 3-dimensional structure, physiology, and complex multicellular nature of actual tumors. However, generating such 3D tissues for each test campaign is labor intensive. In addition, not all researchers have the resources to establish these 3D models. To pave the way, we developed a new platform that offers a range of cryopreserved 3D tumor models in micro plate format allowing for high-content screening. It enables users to start testing compounds within a 3-to-5 days simply by thawing an ARCTis™ plate (Always Ready Cryo Tissues) and following clear instructions. Another advantage of these cryopreserved 3D models derives from the fact that they are made in larger batches which means the start point for compound testing is always the same. This improves data quality, maximizes the test window length, and makes the data comparable across work groups. Currently, our growing portfolio consists of 25 tumor cell lines from ATCC representing the most common solid tumors. Their functionality has been determined based on efficacy tests for each cell line with the apoptotic agent Staurosporine. Various cell lines exhibited compact spheroids with a round morphology, less compact aggregates with non-spherical morphology, or loose cell-cell interaction aggregates, which can correlate with their tumor site of origin. Upon treatment with Staurosporine the dose-response profiles indicated growth inhibition, tumor shrinkage, or tumor cell killing effects based on size assessment and cell metabolic analysis (ATP). Moreover, we demonstrated the robust performance of these assays from plates stored for up to 6 months at -80°C.In conclusion, this groundbreaking approach addresses the limitations of traditional 2D cell cultures by providing a high-throughput, in-plate frozen, 3D cell culture platform. By offering a combination of a more physiologically relevant representation of tumors with a robust frozen-storage and time flexible assay platform our method holds great promise for advancing cancer drug discovery by easing the exploration of complex drug testing screens in vitro. Citation Format: Nils Goedecke, Simon Stroebel, Simon Hutter, Tala Issa, Irina Agarkova, Laure-Anne Ligeon, Olivier Frey. New microplate platform with cryopreserved 3D tumor spheroids for faster and convenient pre-clinical testing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6778.

Case reports of BRAF V600E-mutated tumors effectively treated using the agnostic approach

A tumor-agnostic approach to cancer treatment that implies the selection of agents targeting specific genetic aberrations and signaling pathways regardless of the tumor site of origin represents a new direction in personalized oncology. Pembrolizumab is the first therapy approved for unresectable microsatellite instability-high (MSI-H) tumors of any location. In 2022, the combination of dabrafenib and trametinib was approved by the US Food and Drug Administration (FDA) for the treatment of patients with solid tumors harboring BRAF V600E mutations. Melanomas, colorectal cancers, and non-small cell lung cancers are BRAF-mutated in 60 %, 15 %, and 5–8 % of cases, respectively. BRAF-mutated glioblastoma (3 %), cholangiocarcinoma (5–7 %), pancreatic cancer (1–16 %), and Langerhans cell histiocytosis (57 %) have also been reported.We present two case reports of BRAF-mutated salivary gland and pancreatic cancers in patients with progressive disease despite standard-of-care therapy who were treated with a combination of dabrafenib and trametinib according to the agnostic approach.The presented case reports have demonstrated that the agnostic approach and treatment with BRAF / MEK inhibitors stabilize the disease in patients with BRAF-positive cancers, including those with multiple metastases, and represent an additional therapeutic option for patients with rare BRAF-mutated cancers for which very few pharmacologic options are available.

CNSC-20. MGMT PROMOTER METHYLATED HIGH GRADE GLIOMA WITH DISTANT RECURRENCE AND STABLE ORIGINAL TUMOR SITE: CASE SERIES

Abstract Recurrence pattern in high grade glioma is classified as local and distant recurrence based on distance from original resection cavity and radiation field. We report the first series of three cases of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylated high grade glioma with distant recurrence without local recurrence throughout the disease course. Patient 1: 65 year-old female with WHO grade 4 glioblastoma, isocitrate dehydrogenase enzyme (IDH) wild type (WT), MGMT methylated. She underwent gross total resection followed by Stupp protocol. Postoperative ischemic volume was < 1 ml. Distant recurrence occurred 4 months after completion of Stupp protocol. Patient 2: 55 year-old male with WHO grade 4 glioblastoma, IDH wild type, MGMT methylated. He underwent gross total resection followed by Stupp protocol. Postoperative ischemic volume was 18 ml. Distant recurrence occurred 5 months after completion of Stupp protocol. Patient 3: 31 year-old male with WHO grade 4 astrocytoma, IDH mutant, MGMT promoter methylated. He underwent gross total resection followed by Stupp protocol. Postoperative ischemic volume was 2 ml. Distant recurrence occurred 10 months after completion of Stupp protocol. Distant recurrence is more common in MGMT promoter methylated tumors. All 3 patients in our case series had poor outcomes after distant recurrence without local recurrence at the original tumor site. This observation indicates good local control in MGMT promoter methylated high grade glioma with current standard treatment. For one patient, next generation sequencing (NGS) was available for both original and recurrent tumor and did not reveal any major differences in the genetics of original tumor and distant recurrent tumor other than temozolomide induced high tumor mutational burden in the distant recurrent tumor. Understanding risk factors for distant recurrence in MGMT promoter methylated high grade gliomas and investigating correlations between recurrences will help plan therapeutic strategies to prevent distant recurrence and improve outcomes.

Accuracy of an AI prediction platform in predicting tumor origin: A real-world study.

74 Background: Only four cancers are covered by screening programs. The remaining cancers are diagnosed after a point-of-care presentation to a primavry care physician (PCP). Patients with these cancers typically present with a combination of vague and non-specific symptoms, lacking specificity to a particular tumor type. The difficulties in interpreting these symptoms by PCPs leads to increased diagnostic intervals and the use of invasive diagnostic modalities with unnecessary radiation exposure. Localizing the cancer origin is critical to reduce time to diagnosis in order to improve earlier diagnosis and survival in these cancer types. C the Signs is a clinical platform integrated with electronic health records (EHR) that uses artificial intelligence to help identify patients at risk of cancer. Used by PCPs during a point-of-care assessment, C the Signs analyses the symptoms the patient presents with, alongside clinical data in the EHR, to identify current cancer risk, predict the tumor site of origin, and recommend the most effective diagnostic or referral pathway. The aim of this study is to evaluate the accuracy of C the Signs in predicting cancer origin for patients in a real-world setting. Methods: An observational study was conducted between 1st January 2021 and 31st October 2022 in the National Health Service in England utilizing all patients who were risk-assessed with the C the Signs EHR integrated platform. There was no pre-selection criteria for the patient population assessed. All patients were followed up with for 6 months post-risk assessment to determine if they had a cancer diagnosis. Analysis was performed on the patients who were identified at risk of cancer by the C the Signs platform and subsequently diagnosed with cancer, to establish the cancer origin accuracy. Results: 111,421 patients were risk-assessed by C the Signs, of which 7,360 were diagnosed with cancer. Of the patients diagnosed with cancer, 7,257 patients were identified at risk of cancer by C the Signs (98.67%). The platform predicted cancer origin accurately in 93.2% of patients. The platform was most accurate in predicting cancer origin for brain and CNS, breast, lung, gynecological, head & neck, bowel, skin, and prostate cancers. Conclusions: This study demonstrates how a cancer prediction platform such as C the Signs can be used to accurately detect tumor origin in patients with vague symptoms and facilitate targeted investigations appropriate to the tumor type. Further research is required to identify which cancers can be most accurately detected taking a computational approach.

Identifying primary tumor site of origin for liver metastases via a combination of handcrafted and deep learning features.

Liver is one of the most common sites for metastases, which can occur on account of primary tumors from multiple sites of origin. Identifying the primary site of origin (PSO) of a metastasis can help in guiding therapeutic options for liver metastases. In this pilot study, we hypothesized that computer extracted handcrafted (HC) histomorphometric features can be utilized to identify the PSO of liver metastases. Cellular features, including tumor nuclei morphological and graph features as well as cytoplasm texture features, were extracted by computer algorithms from 175 slides (114 patients). The study comprised three experiments: (1) comparing and (2) fusing a machine learning (ML) model trained with HC pathomic features and deep learning (DL)-based classifiers to predict site of origin; (3) identifying the section of the primary tumor from which metastases were derived. For experiment 1, we divided the cohort into training sets composed of primary and matched liver metastases [60 patients, 121 whole slide images (WSIs)], and a hold-out validation set (54 patients, 54 WSIs) composed solely of liver metastases of known site of origin. Using the extracted HC features of the training set, a combination of supervised machine classifiers and unsupervised clustering was applied to identify the PSO. A random forest classifier achieved areas under the curve (AUCs) of 0.83, 0.64, 0.82, and 0.64 in classifying the metastatic tumor from colon, esophagus, breast, and pancreas on the validation set. The top features related to nuclear and peri-nuclear shape and textural attributes. We also trained a DL network to serve as a direct comparison to our method. The DL model achieved AUCs for colon: 0.94, esophagus: 0.66, breast: 0.79, and pancreas: 0.67 in identifying PSO. A decision fusion-based strategy was deployed to fuse the trained ML and DL classifiers and achieved slightly better results than ML or DL classifier alone (colon: 0.93, esophagus: 0.68, breast: 0.81, and pancreas: 0.69). For the third experiment, WSI-level attention maps were also generated using a trained DL network to generate a composite feature similarity heat map between paired primaries and their associated metastases. Our experiments revealed that epithelium-rich and moderately differentiated tumor regions of primary tumors were quantitatively similar to paired metastatic tumors. Our findings suggest that a combination of HC and DL features could potentially help identify the PSO for liver metastases while at the same time also potentially identify the spatial sites of origin for the metastases within primary tumors.

Outcome of gastric gastrointestinal stromal tumors at National Cancer Institute, Cairo University

Background The purpose of this research was to inspect the tumor landscapes, surgical particulars, and survival distribution of patients of gastric gastrointestinal stromal tumors (GIST) that were surgically removed at the National Cancer Institute, Cairo University. Materials and methods Patients who submitted an application to our clinic and were ultimately diagnosed with gastric GIST were included in this retrospective analysis. Patients’ ages and sexes were recorded, as well as their original tumor sites, histological features, staging, treatments received, treatment methods, and survival rates. Results There were a total of 23 patients, with a female to male ratio of 1 : 3, who had a diagnosis of gastric GIST. They averaged 56 years of age. Tumor sizes, on average was 11.2 cm. In 18 (78.3%) cases, the tumor was located at the distal end, whereas in 5 (21.7%) cases it was located at the proximal end. 19 patients underwent first surgery, whereas only 5 got neoadjuvant treatment focused on the primary tumor. 17 (73.9%) individuals (73.9%) had sleeve gastrectomy, making it the most prevalent operation. 7 days was the typical duration of stay in the hospital. Two patients showed postoperative gastric leakage; the first was treated conservatively, while the second was treated surgically and resulted in a total gastrectomy. With regard to risk categorization, 10 (43.5%) patients had tumors with a high level of risk, 9 (39.1%) had tumors with an intermediate risk, whereas just 4 (17.4%) had tumors with a low risk (Table 3). 16 (69.6%) patients received supplemental targeted treatment. The median duration of patient follow-up was 42.6 months, and all patients were tracked. The cumulative overall survival at 5 years was 82.1%, while the cumulative disease-free survival was 65.4%. Conclusion For individuals who need their gastric GIST removed, extensive local resection that preserves the stomach yields excellent functional and oncological results.

Feasibility study of expressing epcam + /vimentin + CTC in prostate cancer diagnosis.

Prostate cancer (PCa) is one of the most common malignancies in men and one of the leading causes of cancer-related deaths; circulating tumor cells (CTC) are malignant cells that have broken off from original tumor or metastatic sites and extravasated into the blood vessels either naturally or maybe as a consequence of surgical procedures. This study aims to explore the feasibility of liquid biopsy technique to diagnose prostate cancer. We constructed an assay platform integrating magnetic separation and fluorescence in situ hybridization (FISH) to effectively capture prostate cancer CTCs and evaluate the distribution between healthy volunteers and prostate cancer patients, respectively. There was a significant difference in the number of CTCs between the healthy population and prostate cancer patients (P < 0.001). The results of the study showed that the CTCs capture identification system has good sensitivity and specificity in identifying prostate cancer patients. The CTCs test allows us to accurately identify patients who are at high risk for prostate cancer, allowing for early intervention and treating patients effectively.

MGMT Methylated High Grade Glioma with Distant Recurrence and Stable Original Tumor Site: Case Series.

We present three cases of O6-Methylguanine-DNA Methyl-transferase (MGMT) methylated high grade gliomas with distant recurrence. All three patients had a radiographic stability of original tumor site at time of distant recurrence indicating impressive local control with Stupp protocol in patients with a MGMT methylated tumors. All patients had a poor outcome after distant recurrence. For one patient Next Generation Sequencing (NGS) was available for both original and recurrent tumor and did not reveal any difference other than high tumor mutational burden in the distant recurrent tumor. Understanding risk factors of distant recurrence in MGMT methylated tumors and investigating correlations between recurrences will help plan therapeutic strategies to prevent distant recurrence and improve survival of these patients.

Biomarker-Driven Oncology Clinical Trials: Novel Designs in the Era of Precision Medicine

Oncology drug development historically has followed a path of sequential phase I, II, and III clinical trials using traditional trial designs, with the goal of achieving regulatory approval. These studies are often conducted with inclusion criteria that limit enrollment to a single tumor type or tumor site of origin, excluding other patients who might also respond. Increased use of precision medicine targeting biomarkers or specific oncogenic mutations has led to novel clinical trial designs that can evaluate these therapies in a less limited fashion. Master protocols such as basket trials, umbrella trials, and platform trials can, for example, evaluate histology-specific therapies targeting a common oncogenic mutation across multiple tumor types or screen for the presence of multiple different biomarkers rather than a single one. In other cases, they can lead to more rapid evaluation of a drug and evaluate targeted therapies in tumor types for which they are not yet currently indicated. As the use of complex biomarker-based master protocols increases, advanced practitioners must understand these novel trial designs, their advantages and disadvantages, and how their use may advance drug development and maximize the clinical benefits of molecular precision therapy.

Significance of Distinct Liquid Biopsy Compartments in Evaluating Somatic Mutations for Targeted Therapy Selection in Cancer of Unknown Primary.

Cancer of unknown primary (CUP) accounts for 2-5% of all cancer diagnoses, wherein standard investigations fail to reveal the original tumor site. Basket trials allocate targeted therapeutics based on actionable somatic mutations, independent of tumor entity. These trials, however, mostly rely on variants identified in tissue biopsies. Since liquid biopsies (LB) represent the overall tumor genomic landscape, they may provide an ideal diagnostic source in CUP patients. To identify the most informative liquid biopsy compartment, we compared the utility of genomic variant analysis for therapy stratification in two LB compartments (circulating cell-free (cf) and extracellular vesicle (ev) DNA). CfDNA and evDNA from 23 CUP patients were analyzed using a targeted gene panel covering 151 genes. Identified genetic variants were interpreted regarding diagnostic and therapeutic relevance using the MetaKB knowledgebase. LB revealed a total of 22 somatic mutations in evDNA and/or cfDNA in 11/23 patients. Out of the 22 identified somatic variants, 14 are classified as Tier I druggable somatic variants. Comparison of variants identified in evDNA and cfDNA revealed an overlap of 58% of somatic variants in both LB compartments, whereas over 40% of variants were only found in one or the other compartment. We observed substantial overlap between somatic variants identified in evDNA and cfDNA of CUP patients. Nonetheless, interrogation of both LB compartments can potentially increase the rate of druggable alterations, stressing the significance of liquid biopsies for possible primary-independent basket and umbrella trial inclusion.

Association between GPC2 polymorphisms and neuroblastoma risk in Chinese children.

The cell surface glycoprotein glypican 2 (GPC2) has been shown to increase susceptibility to neuroblastoma, which is the most common malignancy in children. However, associations between single nucleotide polymorphism(s) of GPC2 and neuroblastoma risk remain unclarified. We conducted a case-control study to investigate two GPC2 polymorphisms (rs1918353 G>A and rs7799441 C>T) in 473 healthy controls and 402 pediatric patients with neuroblastoma. Single nucleotide polymorphism (SNP) genotyping was conducted on the samples by the TaqMan technique, and the data were subsequently analyzed by the t test, chi-squared test, and logistic regression model. In addition, we further performed stratification analysis by age, sex, tumor site of origin, or clinical stage to control confounding factors. According to the data of dominant models (GA/AA vs. GG: adjusted OR=0.99, 95% CI=0.76-1.29, p=0.943; CT/TT vs. CC: adjusted OR=0.91, 95% CI=0.70-1.19, p=0.498) or other comparisons, as well as the conjoint analysis (adjusted OR=1.22, 95% CI=0.93-1.59, p=0.152), we unfortunately proved that the analysis of single or multiple loci did not support any significant association of GPC2 polymorphisms with susceptibility to neuroblastoma. GPC2 polymorphisms (rs1918353 G>A and rs7799441 C>T) are unable to statistically affect neuroblastoma risk in Chinese children. Therefore, more samples, especially from patients of various ethnic backgrounds, are required to increase the sample size and verify the effect of GPC2 polymorphisms on neuroblastoma risk in the presence of ethnic factor.

Effects of Nutrition Management on Nutritional Status for Advanced Stage of Nasopharyngeal Carcinoma Patients Undergoing Chemoradiation : Literature Review

Malnutrition is an important clinical factor in the development and treatment of cancer. It results from a state when food intake fails to provide energy requirements. Malnutrition is very common in NPC patients because the original tumor site can significantly reduce food intake. International guidelines suggest intensive nutritional counseling (NC) and supplemental oral nutrition as nutritional interventions for head and neck cancer patients with CRT. It was also suggested that if cancer affects eating or swallowing, enteral nutrition (EN) should be given via a feeding tube. The purpose of this study was to investigate the effect of nutritional management in advanced NPC patients with CRT to evaluate nutritional status, and nutritional index and to observe nutritional status (weight, BMI, hemoglobin, albumin, prealbumin, and lymphocytes, and Quality of life (QOL). The method used is the literature review method with a systematic approach by tracing the results of experimental research in English. The articles used are focused on original empirical research articles or research articles that contain results from actual observations or experiments. The results obtained after a review of 3 articles that match the criteria Inclusion was that two studies gave results if nutritional interventions affected NPC patients after undergoing chemoradiation therapy, while one article stated that nutritional interventions did not affect NPC patients.

Tumors of the Digestive System: Comprehensive Review of Ancillary Testing and Biomarkers in the Era of Precision Medicine

Immunotherapy has remained at the vanguard of promising cancer therapeutic regimens due to its exceptionally high specificity for tumor cells and potential for significantly improved treatment-associated quality of life compared to other therapeutic approaches such as surgery and chemoradiation. This is especially true in the digestive system, where high rates of mutation give rise to a host of targetable tumor-specific antigens. Many patients, however, do not exhibit measurable improvements under immunotherapy due to intrinsic or acquired resistance, making predictive biomarkers necessary to determine which patients will benefit from this line of treatment. Many of these biomarkers are assessed empirically by pathologists according to nuanced scoring criteria and algorithms. This review serves to inform clinicians and pathologists of extant and promising upcoming biomarkers predictive of immunotherapeutic efficacy among digestive system malignancies and the ancillary testing required for interpretation by pathologists according to tumor site of origin.

Cáncer de lengua y virus del papiloma humano (VPH)

Introduction: Head & Neck squamous cell carcinoma (HNSCC) is the world’s 6th most common cancer. 400,000 HNSCC were diagnosed in 2005 throughout the world, the most frequently affected site is oral cavity. Alcoholtobacco consumption is the most important risk factor of this neoplasia; nevertheless, since 1983 it was suggested that HPV have a role in HBNSCC mainly in oropharynx (level 1 evidence). Objective: To assess HPV prevalence and types in patients with HNSCC. Material and methods: Presence of HPV was determined by polymerase chain reaction and staged by hybridization in situ. We analyzed stage, tumor site of origin, sex habits, alcohol-tobacco consumption. We performed T test and Fisher’s exact test. We performed a multiple regression analysis for variables’ adjustment. Results: 118 patients; 77 men, 41 women, the most frequent site was oral cavity. Fifty patients (42.3%) were HPV-positive, oropharyngeal and laryngeal cancer patients were the most frequently affected (55% and 50%). HPV-16 was the most frequently isolated (70%). Laryngeal cancer patients suffered the highest ratio of HPV-16 infection (68.7%). Factors associated to HPV (univariate analysis) were: age > 50 years, tobacco-alcohol consumption and male sex, in multivariate analysis none of the variables showed importance (p > 0.5); HPV infection was more frequent in patients with background of alcohol-tobacco (p = 0.6).