Presence Of Metastatic Disease Research Articles

Benefits of Dual-Layer Spectral CT Imaging in Staging and Preoperative Evaluation of Pancreatic Ductal Adenocarcinoma.

Imaging of pancreatic malignancies is challenging but has a major impact on the patients therapeutic approach and outcome. In particular with pancreatic ductal adenocarcinoma (PDAC), usually a hypovascularized tumor, conventional CT imaging can be prone to errors in determining tumor extent and presence of metastatic disease. Dual-layer spectral detector CT (SDCT) is an emerging technique for acquiring spectral information without the need for prospective patient selection or specific protocols, with a detector capable of differentiating high- and low-energy photons to acquire full spectral images. In this review, we present the diagnostic benefits and capabilities of modern SDCT imaging with a focus on PDAC. We highlight the most useful virtual reconstructions in oncologic imaging and their benefits in staging and assessment of resectability in PDAC, including the assessment of tumor extent, vascular infiltration, and metastatic disease. We present imaging examples on a latest-generation SDCT scanner.

Survival Among Post-Operative Non-Small Cell Lung Cancer Patients Receiving Chemoradiotherapy; A Retrospective Analysis

Background: Despite being the second most frequent malignancy, lung cancer is the main reason for cancer-related fatalities. In this study, patients who underwent surgery for Non-Small Cell Lung Cancer and received adjuvant chemoradiotherapy will be evaluated. Patients and Methods: The data of 123 eligible patients who were operated with the diagnosis of Non-Small Cell Lung Cancer between 2000 and 2020 and who were treated with adjuvant chemoradiotherapy were retrospectively analyzed. Results: Of the 123 patients that were included in the study, 111 (90%) were males and 12 (10%) were females. The mean age was 62.11±8.92 (range:33-77) years. According to histological types, 65 (53%) patients were squamous cell carcinoma, 54 (44%) patients were adenocarcinoma and 4 (3%) patients were large cell carcinoma. Fifty-nine (48%) patients had undergone right lobectomy, 43 (35%) patients left lobectomy, 7 (6%) patients right pneumonectomy and 14 (11%) patients had left pneumonectomy. Mean OS time of all patients was 63.34±5.98 (51.62-75.07) months. One, 2, 3 and 5-year survival rates were 89.9%, 66.9%, 56.3% and 40.9%, respectively. There was a significant correlation between the T stage (p=0.05) of the disease and the chemotherapy protocol (p=0.046) and survival. Conclusion: Complete surgical resection remains the most effective treatment for patients with operable Non-Small Cell Lung Cancer. The high risks of distant recurrence brought on by the presence of metastatic disease that went unnoticed prior to surgery, however, restrict the effectiveness of surgical resection. Therefore, postoperative chemoradiotherapy employing constrained areas and contemporary approaches can be advantageous.

Cancer treatment delays among cancer patients living with HIV during the COVID-19 pandemic in the United States.

The COVID-19 pandemic led to care disruptions across the cancer continuum. It is unknown if immunosuppressed patients with cancer, who may be at higher risk for complications of SARS-CoV-2 infection, are disproportionately impacted. Thus, we aimed to compare delays in cancer treatment initiation between people living with HIV (PLWH) and cancer, the general cancer population (GCP), and patients with cancer and a history of solid organ transplant (SOT). Comparisons were made across the period 2 years preceding the pandemic versus the first year of the pandemic. We used data from a real-world electronic health record-derived de-identified database (2018-2021) comprised of US patients with cancer from 800 sites of care across the country. We included patients with 19 different cancer types. We calculated time to cancer treatment initiation (TTI) as the difference between the date of cancer diagnosis and the earliest date that cancer treatment was recorded. The sample included 181 PLWH, 65,073 GCP patients, and 195 patients with a SOT. Difference-in-difference regression models adjusted for age, sex, and presence of metastatic disease at cancer diagnosis revealed a significant increase in delayed TTI among PLWH compared to the GCP during COVID-19 versus prior to COVID-19, with delays increasing by approximately 1 month during the pandemic (DID: 32.6 days [8.9-56.3]; p = 0.007). The increase in TTI for PLWH was observed across treatment modalities, including surgery (DID: 55.1 [28.8-81.3], p < 0.001) and systemic therapy (DID: 30.4 [4.6-56.3], p = 0.021). PLWH experienced significant delays in cancer treatment initiation after diagnosis during the first year of COVID-19, delays that may negatively impact cancer outcomes. These data warrant patient and provider attention as the pandemic continues to impact the US healthcare system.

Medulloblastoma

In the 5th edition of the WHO classification, medulloblastomas, which are representative pediatric brain tumors, are categorized into four groups: WNT, SHH-TP53 wild, SHH-TP53 mutant, and non-WNT/non-SHH, based on their molecular background. While the histopathological findings still hold importance in predicting prognosis, the histopathological classification is no longer utilized in this edition. SHH medulloblastomas are further subdivided into two groups based on the presence or absence of TP53 mutation, as their clinical characteristics and prognosis differ. Group 3 and Group 4 medulloblastomas, recognized as distinct molecular groups in clinical practice, are combined into a single group called "non-WNT/non-SHH", because they lack specific molecular pathway activation. Furthermore, based on methylation profiling, dividing SHH medulloblastoma into four subgroups and non-WNT/non-SHH medulloblastoma into eight subgroups was proposed. Understanding the unique clinical characteristics and prognosis associated with each group is crucial. However, it is important to acknowledge that our current understanding of prognosis is based on treatment approaches guided by clinical risk factors such as postoperative residual tumor volume and the presence of metastatic disease. This molecular-based classification holds promise in guiding the development of optimal treatment strategies for patients with medulloblastoma.

Management of Medullary Thyroid Cancer: Patterns of Recurrence and Outcomes of Reoperative Surgery.

There remains uncertainty regarding the optimal extent of initial surgery and management of recurrent disease in medullary thyroid cancer (MTC). We aim to describe the patterns of disease recurrence and outcomes of the reoperative surgery in a cohort of consecutively treated patients at a specialized tertiary referral center. A retrospective cohort study of 235 surgically treated patients with MTC at a tertiary referral center was performed using prospectively collected data. In the study period 1986-2022, 235 patients underwent surgery for MTC. Of these, 45 (19%) patients had reoperative surgery for cervical nodal recurrence at a median (range) 2.1 (0.3-16) years following the index procedure. After a median follow-up of 4 years, 38 (84%) patients remain free of structural cervical recurrence, although 15 (33%) underwent 2 or more reoperative procedures. No long-term complications occurred after reoperative surgery. Local cervical recurrence was independently predicted by pathologically involved nodal status (OR 5.10, P = .01) and failure to achieve biochemical cure (OR 5.0, P = .009). Local recurrence did not adversely affect overall survival and was not associated with distant recurrence (HR 0.93, P = .83). Overall survival was independently predicted by high pathological grade (HR 10.0, P = .002) and the presence of metastatic disease at presentation (HR 8.27, P = 0018). Loco-regional recurrence in MTC does not impact overall survival, or the development of metastatic disease, demonstrating the safety of the staged approach to the clinically node-negative lateral neck. When recurrent disease is technically resectable, reoperative surgery can be undertaken with minimal morbidity in a specialized center and facilitates structural disease control.

Multidisciplinary Approach to the Diagnosis of Occult Primary Neuroendocrine Neoplasm: A Clinical Challenge.

Approximately 11% to 14% of subjects with neuroendocrine neoplasms (NENs) have metastatic lesions with unknown primary origin (UPO), with the majority of UPO-NENs found in the small bowel. Herein, we assessed the available literature on UPO-NENs, focusing on clinical presentation and diagnostic techniques to identify the primary site. The identification of the primary tumor is important as it affects the prognosis; however, the clinical presentation can be non-specific in non-functioning forms. In the presence of metastatic disease, the histological sample is fundamental to obtain immunohistochemical markers that might orientate the clinician in the search for the primary tumor through radiology, functional imaging and endoscopic techniques. In summary, multidisciplinary management plays a key role in UPO-NENs, even more than in other NENs. Molecular biology and gene-expression profiling represent areas of great interest which might be developed in the near future for both the diagnosis and the treatment of these neoplasms.

SP6.5 Outcomes in Oesophagogastric Cancer up to 18 months following the COVID-19 pandemic

Abstract Aims COVID-19 has negatively influenced oesophago-gastric (OG) cancer prognosis with stage migration described during the first six months of the pandemic. This study investigated the medium term effect of the national lockdown on diagnosis, management and outcomes. Methods A retrospective cohort study of all newly diagnosed OG cancers in a single regional MDT between 1 October 2019 and 30 September 2021. Patients were divided into four 6-month period based upon date of first MDT discussion in relation to the first UK national lockdown: pre-lockdown, 0-6, 6-12 and 12-18 months post-lockdown. Electronic health records were reviewed and results compared. Result 664 patients with OG cancers were included. Median age was 71 years (62-77) and 445 (67%) were male. 502 (76%) had adenocarcinoma. Compared with pre-lockdown, patients in the 0-6-months group were significantly older (p&amp;lt;0.05), symptomatic (p&amp;lt;0.05), and had stage migration with increased metastatic disease (p&amp;lt;0.05), palliative treatment intent (p&amp;lt;0.001) and reduced survival (p&amp;lt;0.05). Compared with pre-lockdown, there was no difference in patients presenting in the 12-18 months group in terms of age (p=0.927), sex (p=0.461), performance status (p=0.666), presence of metastatic disease (p=0.971) and treatment intent (p=0.123). However, more patients in this group were symptomatic (p=0.025), presented as emergencies (p=0.032) and had a poorer overall survival (p&amp;lt;0.05). Conclusion Patients presenting 12-18 months after the initial lockdown are still experiencing poorer overall survival than those pre-pandemic. Identification and addressment of the factors contributing to the continued poor outcomes following COVID-19 is urgently required to return overall patient survival to the pre-pandemic level.

Genetic mutations in smoking-associated prostate cancer.

Tobacco smoking is known to cause cancers potentially predisposed by genetic risks. We compared the frequency of gene mutations using a next generation sequencing database of smokers and nonsmokers with prostate cancer (PCa) to identify subsets of patients with potential genetic risks. Data from the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (GENIE) registry was analyzed. The GENIE registry contains clinically annotated sequenced tumor samples. We included 1832 men with PCa in our cohort, categorized as smokers and nonsmokers, and compared the frequency of mutations (point mutations, copy number variations, and structural variants) of 47 genes with more than 5% mutation rate between the two categories and correlated with overall survival using logistic regression analysis. Overall, 1007 (55%) patients were nonsmokers, and 825 (45%) were smokers. The mutation frequency was significantly higher in smokers compared to nonsmokers, 47.6% and 41.3%, respectively (p = 0.02). The median tumor mutational burden was also significantly higher in the samples from smokers (3.59 mut/MB) compared to nonsmokers (1.87 mut/MB) (p < 0.001). Patients with a smoking history had a significantly higher frequency of PREX2, PTEN, AGO2, KMT2C, and a lower frequency of adenomatous polyposis coli (APC) and KMT2A mutations than compared to nonsmokers. The overall mortality rate (28.5% vs. 22.8%) was significantly higher among smokers (p = 0.006). On a multivariate logistic regression analysis, the presence of metastatic disease at the time of diagnosis (OR: 2.26, 95% CI: 1.78-2.89, p < 0.001), smoking history (OR: 1.32, 95% CI: 1.05-1.65, p = 0.02), and higher frequency of PTEN somatic gene mutation (OR: 1.89, 95% CI: 1.46-2.45, p < 0.001) were independent predictors of increased overall mortality among patients with PCa. Patients with PTEN mutation had poorer overall survival compared to men without PTEN mutations: 96.00 (95% CI: 65.36-113.98) and 120.00 (95% CI: 115.05-160.00) months, respectively (p < 0.001) irrespective of smoking history although the G129R PTEN mutation was characteristically detected in smokers. PCa patients with a tobacco smoking history demonstrated a significantly higher frequency of somatic genetic mutations. Whereas mutations of PREX2, KMT2C, AGO2, and PTEN genes were higher in smokers, the APC and KMT2A mutations were higher in nonsmokers. The PTEN somatic gene mutation was associated with increased overall mortality among patients with PCa irrespective of smoking history. We found that G129R PTEN mutation known to reduce the PTEN phosphatase activity and K267Rfs*9 a frameshift deletion mutation in the C2 domain of PTEN associated with membrane binding exclusively detected in smokers and nonsmokers, respectively. These findings may be used to further our understanding of PCa associated with smoking.

Extremity Rhabdomyosarcoma-An Integrated Clinicopathologic and Genomic Study to Improve Risk Stratification.

Extremity rhabdomyosarcoma (RMS) is associated with a very poor outcome compared with other sites, mainly because of its high incidence of alveolar histology and regional lymph node involvement. To better define prognostic markers in this clinical subset, we investigated our experience of 61 patients with extremity RMS treated at our tertiary cancer center for the past 2 decades. The patients had a median age of 8 years at diagnosis, equal gender distribution, and two-thirds occurred in the lower extremity. Most (85%) patients had FOXO1 fusion-positive alveolar RMS (ARMS), with 70% having a PAX3::FOXO1 transcript. Remaining were seven patients with fusion-negative embryonal RMS (ERMS) and two with MYOD1-mutant spindle cell/sclerosing RMS (SRMS). In 40% of the patients, material was available for DNA-based targeted sequencing using MSK-IMPACT cancer gene panel. One-third of patients presented with localized disease at diagnosis while the remaining had regional nodal (18%) or distant metastases (51%). Metastatic disease, high-risk group, and age 10 years or older significantly affected the overall survival (OS; hazard ratio [HR], 2.68 [P = .004], 2.78 [P = .010] and 2.26 [P = .034], respectively). Although the presence of metastatic disease had a dismal impact on 5-year EFS and OS (19% and 29%, respectively), nodal involvement had a comparatively lower impact on 5-year EFS and 5-year OS (43% and 66%, respectively). PAX3::FOXO1 ARMS had worse prognosis and afflicted older children compared with PAX7::FOXO1 (HR = 3.45, P = .016). The most common events in the ARMS group included MED12 alterations, CDK4 amplifications, and CDKN2A deletions (8%-17%). The latter two abnormalities were mutually exclusive, enriched for acral and high-risk lesions, and correlated with poor outcome on OS (P = .02). Our data provide rationale for considering the integration of molecular abnormalities to refine risk stratification in extremity RMS.

Alliance A022101: A pragmatic, randomized phase III trial evaluating total ablative therapy for patients with limited metastatic colorectal cancer: Evaluating Radiation, Ablation, and Surgery (ERASur).

TPS3629 Background: For patients with oligometastatic colorectal cancer (CRC), aggressive local therapy of isolated metastases, particularly in the liver, has been associated with long-term progression-free survival and overall survival (OS) primarily based on retrospective evidence. However, in patients with limited metastatic CRC that is deemed inoperable or those with additional disease outside of the liver or lungs, the role of local ablative therapies, including microwave ablation (MWA) and stereotactic body radiation therapy (SBRT), to render patients disease free is less clear. Further, despite the long history of treating oligometastatic CRC with local therapy, which is provider biased and not evidence based, questions remain regarding the benefit of extending the paradigm of metastatic directed therapy to patients with more extensive disease. This trial seeks to use a pragmatic multimodality approach that mirrors the current clinical dilemma. This study is designed to evaluate the safety and efficacy of adding total ablative therapy (TAT) of all sites of disease to standard of care systemic treatment in those with limited metastatic CRC. Methods: A022101 is a National Clinical Trials Network randomized phase III study planned to enroll 364 patients with newly diagnosed metastatic CRC (BRAF wild-type, microsatellite stable) with ≤4 sites of metastatic disease on baseline imaging. Liver-only metastatic disease is not permitted, and lesions must be amenable to any combination of surgical resection, MWA, and/or SBRT with SBRT required for at least one lesion. Patients receive first-line systemic therapy for 4-6 months and are then randomized 1:1, stratified by number of metastatic organ sites (1-2 vs. 3-4), timing of metastatic disease diagnosis (de novo vs. secondary), and presence of metastatic disease outside the liver and lungs in at least one site. Patients in Arm 1 will receive TAT which consists of treatment of all metastatic sites with SBRT ± MWA ± surgical resection followed by standard of care systemic therapy. Patients in Arm 2 will continue with standard of care systemic therapy alone. The primary endpoint is OS. Secondary endpoints include event-free survival, treatment-related toxicities, and local recurrence with exploratory biomarker analyses. The study needs 346 evaluable patients combined in the 2 arms to demonstrate an improvement in OS with a hazard ratio of 0.7 to provide 80% power with a one-sided alpha of 5%. The trial utilizes a group sequential design with two interim analyses (25% and 50% of events) for futility. The trial activated in January 2023 and recruitment is ongoing. Support: U10CA180821, U10CA180882; https://acknowledgments.alliancefound.org. U10CA180820 (ECOG-ACRIN); U10CA180868 (NRG); U10CA180888 (SWOG); Clinicaltrials.gov identifier: NCT05673148 Clinical trial information: NCT05673148 .

Abstract #1398490: The Enigma of Malignant Struma Ovarii

Struma ovarii is a rare form of ovarian germ cell tumor with at least 50% of mature thyroid tissue. Most of them are benign with malignant transformation occurring in only < 5% of tumors. Malignant struma ovarii presenting with follicular-type carcinoma is extremely rare. We present an interesting case of malignant struma ovarii with follicular carcinoma. 66-year-old female was referred with a diagnosis of malignant struma ovarii. She was previously evaluated at emergency room when she presented with right lower quadrant abdominal pain. CT scan done at that time revealed 6.5 cm right adnexal lesion which increased from 3.9 cm from 13 years ago. She subsequently underwent total abdominal hysterectomy with bilateral salpingo-oopherectomy with pathology showing 10.5 cm poorly differentiated follicular thyroid carcinoma with in struma ovarii component of an ovarian teratoma. There was capsular and focal angioinvasion. PET/CT done later was negative for malignancy and the thyroid ultrasound showed no thyroid nodules or neck adenopathy. Laboratory examination revealed TSH and free T4 levels within normal range. She underwent total thyroidectomy and then underwent recombinant human thyrotropin stimulated radioactive iodine treatment with 150 mCi of I-131. Post therapy whole body scan showed increased radiotracer activity in the left pelvic region for which additional SPECT-CT was performed which confirmed that the increased radiotracer activity along the anterior aspect of the left superior iliac bone was misregistered bowel and there was no destructive osseous lesion involving the left iliac bone on the corresponding CT. There is no other evidence of focal iodide activity to suggest extra-thyroidal disease. She is being continued on levothyroxine 100 mcg. Post treatment stimulated thyroglobulin levels were 0.7 ng/mL with negative thyroglobulin antibodies. Because of its rarity and absence of consensus on diagnosis and treatment, there are no established guidelines for management of malignant struma ovarii. The decision to perform thyroidectomy and administer radioiodine after oophorectomy are based on the reports from case series and depends on the presence of metastatic disease and the risk of recurrence. In our patient, large size of the tumor and presence of poorly differentiated follicular carcinoma indicated higher risk of recurrence warranting total thyroidectomy and radioiodine treatment. As she had good treatment response, goal of levothyroxine therapy is to maintain between 0.1-0.5 mU/L. Monitoring of serum stimulated thyroglobulin annually is recommended for 2 years after surgery and, if negative, unstimulated levels annually thereafter.

MP17-19 GENE MUTATIONS AMONG PROSTATE CANCER PATIENTS WITH A SMOKING HISTORY

You have accessJournal of UrologyCME1 Apr 2023MP17-19 GENE MUTATIONS AMONG PROSTATE CANCER PATIENTS WITH A SMOKING HISTORY Ahmed El-shafie, Allison H. Feibus, Mohammed Al-Toubat, Navid Lelani, SeyedBehzad Jazayeri, Kashyap Koul, Robert A. Marino, Mark Bandyk, Joseph Costa, and K. C. Balaji Ahmed El-shafieAhmed El-shafie More articles by this author , Allison H. FeibusAllison H. Feibus More articles by this author , Mohammed Al-ToubatMohammed Al-Toubat More articles by this author , Navid LelaniNavid Lelani More articles by this author , SeyedBehzad JazayeriSeyedBehzad Jazayeri More articles by this author , Kashyap KoulKashyap Koul More articles by this author , Robert A. MarinoRobert A. Marino More articles by this author , Mark BandykMark Bandyk More articles by this author , Joseph CostaJoseph Costa More articles by this author , and K. C. BalajiK. C. Balaji More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003237.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Tobacco smoking has been established as a risk factor for a majority of cancers, representing one of the most important modifiable risk factors. However, the association between smoking and prostate cancer (PCa) remains unclear. We compared gene mutations using a next generation sequencing (NGS) database of smokers and non-smokers with PCa. METHODS: Data is derived from the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (GENIE) registry. We included 1832 men with PCa in our study cohort, categorized as either smokers or non/never smokers. We compared the frequency of mutations (point mutations, copy number variations and structural variants) of 47 genes between the 2 groups. We also studied the association of the gene mutations with overall survival. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with mortality. RESULTS: Within the study cohort, 1007 (55%) patients were non-smokers and the remaining 825 (45%) were smokers. Patients with a smoking history had a higher percentage of somatic mutations in PREX2 (p=0.018), PTEN (p=0.02), AGO2 (p=0.03), and KMT2C (p=0.04) compared to non-smokers. In contrast, non-smokers had a higher percentage of somatic mutations in APC (p=0.02) and KMT2A (p=0.04) compared to smokers. The mortality rate was significantly higher among the smoker population (p=0.006). The presence of metastatic disease at the time of diagnosis (OR 2.26, p<0.001), smoking history (OR 1.32, p=0.02), and PTEN somatic gene mutation (OR 1.89, p<0.001) were independent predictors of mortality among patients diagnosed with PCa (Table 1). CONCLUSIONS: PCa patients with a tobacco smoking history had significantly higher somatic mutations of PREX2, KMT2C, AGO2, and PTEN genes. Moreover, PTEN somatic gene mutation is linked to mortality among patients with PCa (Figure 1). Source of Funding: none © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e220 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ahmed El-shafie More articles by this author Allison H. Feibus More articles by this author Mohammed Al-Toubat More articles by this author Navid Lelani More articles by this author SeyedBehzad Jazayeri More articles by this author Kashyap Koul More articles by this author Robert A. Marino More articles by this author Mark Bandyk More articles by this author Joseph Costa More articles by this author K. C. Balaji More articles by this author Expand All Advertisement PDF downloadLoading ...

Breast-like cancer of unknow primary : Implications for radiological diagnostics

Cancer of unknown primary (CUP) is defined by the presence of metastatic disease with an undetectable primary tumor at the time of presentation despite standard-of-care imaging. Although the prognosis of most CUP patients is poor, certain subgroups with more favorable prognosis have been defined. Women with isolated axillary lymph node metastases and confirmed histologic adenocarcinoma or poorly differentiated subtype, no other distant metastases, and no evidence of aprimary cancer including primary breast carcinoma evaluated by clinical examination, computed tomography of thorax and abdomen, mammography, breast ultrasound, and breast magnetic resonance imaging (MRI) represent apotentially curable subgroup of patients with CUP. Breast MRI is the most important radiological modality in the diagnostic workup of breast-like CUP to exclude aprimary cancer in the breast. Breast-like CUP patients are treated according to guidelines for patients with node-positive breast cancer. Standard-of-care adjuvant systemic therapy should be given. Axillary lymph node dissection (ALND) is indicated. If no primary cancer in the breast is detected, surgery of the ipsilateral breast should not be performed. Radiotherapy of the ipsilateral breast and supra-/infraclavicular lymph nodes should be discussed.

Immune checkpoint inhibitors and Chimeric Antigen Receptor (CAR)-T cell therapy: Potential treatment options against Testicular Germ Cell Tumors.

Germ cell tumors (GCTs) represent a heterogeneous neoplasm family affecting gonads and rarely occurring in extragonadal areas. Most of patients have a good prognosis, often even in the presence of metastatic disease; however, in almost 15% of cases, tumor relapse and platinum resistance are the main challenges. Thus, novel treatment strategies with both improved antineoplastic activity and minor treatment-related adverse events compared with platinum are really expected. In this context, the development and the high activity demonstrated by immune checkpoint inhibitors in solid tumors and, subsequently, the interesting results obtained from the use of chimeric antigen receptor (CAR-) T cell therapy in hematological tumors, have stimulated research in this direction also in GCTs. In this article, we will analyze the molecular mechanisms underlying the immune action in the development of GCTs, and we will report the data from the studies that tested the new immunotherapeutic approaches in these neoplasms.

Orthotopic Implantation of Patient-Derived Cancer Cells in Mice Recapitulates Advanced Colorectal Cancer.

Over the last decade, more sophisticated preclinical colorectal cancer (CRC) models have been established using patient-derived cancer cells and 3D tumoroids. Since patient derived tumor organoids can retain the characteristics of the original tumor, these reliable preclinical models enable cancer drug screening and the study of drug resistance mechanisms. However, CRC related death in patients is mostly associated with the presence of metastatic disease. It is therefore essential to evaluate the efficacy of anti-cancer therapies in relevant in vivo models that truly recapitulate the key molecular features of human cancer metastasis. We have established an orthotopic model based on the injection of CRC patient-derived cancer cells directly into the cecum wall of mice. These tumor cells develop primary tumors in the cecum that metastasize to the liver and lungs, which is frequently observed in patients with advanced CRC. This CRC mouse model can be used to evaluate drug responses monitored by microcomputed tomography (µCT), a clinically relevant small-scale imaging method that can easily identify primary tumors or metastases in patients. Here, we describe the surgical procedure and the required methodology to implant patient-derived cancer cells in the cecum wall of immunodeficient mice.

Is there a Role for Primary Surgical Resection in the Palliative Rectal Cancer Setting: A Systematic Re-view

Introduction: There are over 42,000 new cases of colorectal cancer diagnosed every year in the UK alone, a third of those being rectal in origin. Although there has been significant progress in the treatment of rectal cancer, overall, 5-year survival can still be as low as 17% for those with advanced disease. We aimed to assess the impact on of overall survival and quality of life of primary tumour resection in the palliative setting. Method: A literature search was performed using Pubmed and Cochrane databases in March 2022. Bias was assessed using the Joanna Briggs institute checklist. Results: Seven papers were included in the review; all retrospective cohort. A total of 809 patients underwent rectal resection in the presence of metastatic disease +/- adjuvant therapy. The median age was 61years, 59.7% male. 68.6% of patients presented with liver metastasis at the time of diagnosis. The most commonly reported symptoms preoperatively were bleeding and tenesmus. 4-50% of patients in each cohort underwent neoadjuvant therapy. Highest 30-day mortality reported was 7.3%. Both studies comparing resection v none demonstrated a higher overall survival for those undergoing surgery, with one showing 1year overall survival 65v20%. Quality of life was not addressed across the literature. Conclusion: Although there is some evidence to show a favourable overall survival for patients undergoing primary tumour resection in the palliative setting, this data is mainly old and across a heterogeneous population. A larger scale prospective study would be required to assess its potential role and impact upon quality of life.

Wilms tumor in children: A multivariate analysis of prognostic factors, with emphasis on inferior vena cava/right atrium extension. Results from a single-center study

BackgroundTo identify prognostic factors for overall survival through the analysis of 132 patients with Wilms tumor followed at a single center, with emphasis on the inferior vena cava/right atrium extension. MethodsRetrospective analysis of overall survival using logistic regression models and including age, sex, clinical features, associated syndromes, comorbidities, tumor size before chemotherapy, stage, presence of metastatic disease and its site, invasion of adjacent structures, inferior vena cava/right atrium extension, laterality, tumor histology, chemotherapy protocol, and radiotherapy as potential risk factors. ResultsFrom January 2000 through November 2021, 132 patients met the inclusion criteria, 64 females and 68 males; 15 (11.4%) patients presented with tumoral extension to inferior vena cava/right atrium and 44 had metastatic disease (33.3%). Based on logistic regression, the factors correlating to a fatal outcome were male sex (p = 0.046), high risk histology (p = 0.036), and the presence of metastatic disease (p = 0.003). None of the patients presenting inferior vena cava/right atrium extension died (p = 0.992). In a specific analysis of metastatic sites, hepatic metastasis alone showed correlation with a fatal outcome (p = 0.001). ConclusionThese results underline the importance of identifying and treating metastatic disease and high-risk tumors. The female gender as a potential driver for a less aggressive disease is a new finding that deserves further investigation. The accurate identification of inferior vena cava/right atrium extension, subsequent preoperative chemotherapy, and resection with a skilled team promoted survival rates of all patients. Level of evidenceII.

Best practices in surgical and nonsurgical management of head and neck Merkel cell carcinoma: An update.

Merkel cell carcinoma (MCC) is a rare, highly aggressive cutaneous neuroendocrine carcinoma. Controversy exists regarding optimal management of MCC as high-quality randomized studies and clinical trials are limited, and physicians are bound to interpret highly heterogeneous, retrospective literature in their clinical practice. Furthermore, the rising incidence and notably poor prognosis of MCC urges the establishment of best practices for optimal management of the primary tumor and its metastases. Herein, we summarized the relevant evidence and provided an algorithm for decision-making in MCC management based on the latest 2021 National Comprehensive Cancer Network guidelines. Additionally, we report current active MCC clinical trials in the United States. The initial management of MCC is dependent upon the pathology of the primary tumor and presence of metastatic disease. Patients with no clinical evidence of regional lymph node involvement generally require sentinel node biopsy (SLNB) while clinically node-positive patients should undergo fine needle aspiration (FNA) or core biopsy and full imaging workup. If SLNB or FNA/core biopsy are positive, a multidisciplinary team should be assembled to discuss if additional node dissection or adjuvant therapy is necessary. Wide local excision is optimal for primary tumor management and SLNB remains the preferred staging and predictive tool in MCC. The management of MCC has progressively improved in the last decade, particularly due to the establishment of immunotherapy as a new treatment option in advanced MCC. Ongoing trials and prospective studies are needed to further establish the best practices for MCC management.

Prevalence, characteristics and mortality of cancer patients undergoing pericardiocentesis in the United States between 2004 and 2017.

Pericardiocentesis is undertaken in patients with cancer for diagnostic and therapeutic purposes. However, there are limited data on the frequency, characteristics and mortality of patients with different cancers undergoing pericardiocentesis. All hospitalisations of adult cancer patients (≥18 years) in the US National Inpatient Sample between January 2004 and December 2017 were included. The cohort was stratified by discharge code of pericardiocentesis and cancer, using the International Classification of Diseases. The prevalence of pericardiocentesis, patient characteristics, cancer types and in-hospital all-cause mortality were analysed between cancer patients undergoing pericardiocentesis versus not. A total of 19,773,597 weighted cancer discharges were analysed, out of which 18,847 (0.1%) underwent pericardiocentesis. The most common cancer types amongst the patients receiving pericardiocentesis were lung (51.3%), haematological (15.9%), breast (5.4%), mediastinum/heart (3.2%), gastroesophageal (2.2%) and female genital cancer (1.8%), whilst 'other' cancer types were present in 20.2% patients. Patients undergoing pericardiocentesis had significantly higher mortality (15.6% vs. 4.2%, p < 0.001) compared to their counterparts. The presence of metastatic disease (aOR 2.67 95% CI 1.79-3.97), weight loss (aOR 1.48 95% CI 1.33-1.65) and coagulopathy (aOR 3.22 95% CI 1.63-6.37) were each independently associated with higher mortality in patients who underwent pericardiocentesis. Pericardiocentesis is an infrequent procedure in cancer patients and is most commonly performed in patients with lung, haematological and breast cancer. Cancer patients undergoing pericardiocentesis have increased mortality, irrespective of the underlying cancer type.

Extended radical cholecystectomy with curative potential for well selected locally advanced carcinoma gall bladder: a case report and review of literature

Gallbladder cancer is an aggressive malignancy that is associated with a poor prognosis. While surgical resection provides the only curative option, the majority of patients are not considered resectable due to locally advanced disease and presence of metastatic disease at the time of presentation. Here we presented a case of 46-year-old female with symptoms and initial workup suggestive of obstructive jaundice with cholestasis. PET-CT demonstrated heterogeneously enhancing mass lesion arising from neck of gallbladder and involving adjacent liver parenchyma with FDG avid para-aortic nodes. Liver biopsy confirmed adenocarcinoma, ERCP revealed tight hilar structure and CBD stent was placed. Patient was diagnosed with cT4, N2 carcinoma gall bladder and received two cycles of neoadjuvant chemotherapy (NACT) with gemcitabine and cisplatin. In view of localized and stable disease following NACT, patient underwent radical cholecystectomy with wide liver resection involving segment 4b and 5 with hepatoduodenal, portocaval and aortocaval lymph node dissection. Patient had post-operative complications, managed conservatively. On follow up patient had improved appetite, gained weight adequately, received adjuvant chemotherapy and is disease free till date. Carefully selected patients may benefit from an aggressive surgical approach following upfront systemic chemotherapy.