Presence Of Metastatic Disease Research Articles

Refractory Stage M Ganglioneuroblastoma With Bone Metastases and a Favorable, Chronic Course of Disease: Description of a Patient Cohort.

Refractory stage M neuroblastoma (NB) is associated with a poor prognosis and a progressive course of disease. Here, we describe a unique group of patients with a discrepant clinical course. Seven histologically confirmed ganglioneuroblastoma (GNB) (n=6) and differentiating NB (n=1) patients were identified who were diagnosed with stage M disease based on iodine-123-metaiodobenzylguanidine avid bone metastases. Six patients started on high-risk treatment, without tumor response (stable disease). Treatment was discontinued before the start of consolidation treatment because of refractory response in all patients. Unexpectedly, after cessation of treatment no progression of disease occurred. In 2 patients, the primary tumors expanded (>25%) very slowly during 1.5 and 3 years, and remained stable thereafter. Metabolically, a slow decrease of urinary homovanillic acid and vanillylmandelic acid levels and iodine-123-metaiodobenzylguanidine avidity was observed. All patients are alive with presence of metastatic disease after a median follow-up of 17 years (range: 6.7 to 27 y). Interestingly, at diagnosis, 6 patients were asymptomatic, 6 patients had GNB morphology, and 5 patients had meningeal metastases. These are all features seen in only a small minority of stage M patients. This GNB entity illustrates the clinical heterogeneity of neuroblastic tumors and can be used to further study the developmental origin of different NB subtypes.

Tumor Biology Impacts Survival in Surgically Managed Primary Hepatic Vascular Malignancies

BackgroundHepatic angiosarcoma (AS) and hepatic epithelioid hemangioendothelioma (HEHE) are rare primary hepatic vascular malignancies (PHVM) that remain poorly understood. To guide management, we sought to identify factors and trends predicting survival after surgical intervention using a national database. Materials and methodsIn a retrospective analysis of the National Cancer Database patients with a diagnosis of PHVM were identified. Clinicopathologic factors were extracted and compared. Overall survival (OS) was estimated and predictors of survival were identified. ResultsThree hundred ninty patients with AS and 216 with HEHE were identified. Only 16% of AS and 36% of HEHE patients underwent surgery. The median OS for patients who underwent surgical intervention was 97 months, with 5-year OS of 30% for AS versus 69% for HEHE patients (P< 0.001). Tumor biology strongly impacted OS, with AS histology (Hazard Ratio [HR] of 3.61 [1.55-8.42]), moderate/poor tumor differentiation (HR = 3.86 [1.03-14.46]) and tumor size (HR = 1.01 [1.00-1.01]) conferring worse prognosis. The presence of metastatic disease in the surgically managed cohort (HR = 5.22 [2.01-13.57]) and involved surgical margins (HR = 3.87 [1.59-9.42]), were independently associated with worse survival. ConclusionsIn this national cohort of PHVM, tumor biology, in the form of angiosarcoma histology, tumor differentiation and tumor size, was strongly associated with worse survival after surgery. Additionally, residual tumor burden after resection, in the form of positive surgical margins or the presence of metastasis, was also negatively associated with survival. Long-term clinical outcomes remain poor for patients with the above high-risk features, emphasizing the need to develop effective forms of adjuvant systemic therapies for this group of malignancies.

A Case for Worldwide Mass Immunization with MMR to Limit Deaths from COVID-19

It is generally accepted that deaths related to Covid-19 are centred on adults about their 70’s which might be reason for the association with co-morbidities like cardiovascular disease, obesity, diabetes mellitus, chronic kidney disease, chronic lung disease, smoking, cancer especially hematologic malignancies, lung cancer and presence of metastatic disease. The strength of the evidence for these associations is still being investigated. One plausible explanation for all these associations may be their increased risk for micro-thrombotic events in the microvascular circulation of vital organ systems as well as increased risk for thrombo-embolic disease in general. Male patients appear to have higher death rates in China, Italy, Denmark and the US. Black, Hispanic and South Asian patients have increased mortality in the US and this may be related to the disparities in healthcare indices in these populations as well as their higher representation in the “essential work-forces” and associated increased exposure to infection.

A population-based study on incidence, treatment, and survival in ampullary cancer in the Netherlands

IntroductionAmpullary cancer is rare and as a result epidemiological data are scarce. The aim of this population-based study was to determine the trends in incidence, treatment and overall survival (OS) in patients with ampullary adenocarcinoma in the Netherlands between 1989 and 2016. MethodsPatients diagnosed with ampullary adenocarcinoma were identified from the Netherlands Cancer Registry. Incidence rates were age-adjusted to the European standard population. Trends in treatment and OS were studied over (7 years) period of diagnosis, using Kaplan-Meier and Cox regression analyses for OS and stratified by the presence of metastatic disease. ResultsIn total, 3840 patients with ampullary adenocarcinoma were diagnosed of whom, 55.0% were male and 87.1% had non-metastatic disease. The incidence increased from 0.59 per 100,000 in 1989–1995 to 0.68 per 100,000in 2010–2016. In non-metastatic disease, the resection rate increased from 49.5% in 1989–1995 to 63.9% in 2010–2016 (p < 0.001). The rate of adjuvant therapy increased from 3.1% to 7.9%. In non-metastatic disease, five-year OS (95% CI) increased from 19.8% (16.9–22.8) in 1989–1995 to 29.1% (26.0–31.2) in 2010–2016 (logrank p < 0.001). In patients with metastatic disease, median OS did not significantly improve (from 4.4 months (3.6–5.0) to 5.9 months (4.7–7.1); logrank p = 0.06). Cancer treatment was an independent prognostic factor for OS among all patients. ConclusionBoth incidence and OS of ampullary cancer increased from 1989 to 2016 which is most likely related to the observed increased resection rates and use of adjuvant therapy.

Cáncer de mama

Breast cancer represents the main cause of death from malignant tumors in women. It is considered a multifactorial entity, linked to the hormonal and reproductive factors of the patients. The most common clinical presentation is the presence of a painless mass in the breast. The diagnosis is based on the triad of clinical assessment, imaging test and biopsy, highlighting mammography as an essential test in population screening. The prognosis depends on the biological subtype and the tumor stage at diagnosis. The objectives and the modality of treatment varies depending on the tumor stage. In the treatment of early stages, which has a curative intention, local treatment with surgery and radiotherapy is important, as well as adjuvant or neoadjuvant systemic treatment with chemotherapy, hormone therapy, biological treatment and/or combinations of them. In the presence of metastatic disease, the goal of treatment is palliative. In this situation, classic therapies with chemotherapy and hormonal therapy have been joined in recent years by the incorporation of new therapies.

Analysis of germline alterations and testing patterns in Hispanic men with prostate cancer.

Background: Little is known about the prevalence of germline alterations in Hispanic men with prostate cancer (PC). Here, we examine the rates of germline alterations in Hispanic men with PC, compare these rates to non-Hispanic white men, and examine factors associated with clinicians offering testing. Methods: Single center, retrospective analysis of patients (pts) with PC who self-identify as Hispanic and meet the NCCN criteria for germline testing. Pts who consented for testing underwent a commercial multigene germline assay. Among those tested, the proportion of pathogenic alterations and variants of uncertain significance (VUS) were computed in 20 genes associated with germline alterations in PC. This was compared to non-Hispanic white (NHW) pts who also underwent germline testing. Multivariate logistic regression was performed to assess clinical and demographic factors associated with clinicians offering germline testing and/or genetics referral. Results: We identified 136 Hispanic men with PC eligible for germline testing between 2018-2020. 26.1% (n=34) of pts underwent germline testing and among those tested, 14.7% (n=5/34) had a pathogenic alteration detected. Median age of the cohort was 70 years and 46.3% (n=63) had metastatic disease. Spanish was the primary language for 50% (n=68) and 14.0% (n=19) of pts had at least 1 first-degree relative with PC. Alterations were detected in ATM (n=2), CHEK2 (n=1), MSH2 (n=1), MSH6 (n=1). When stratified by disease status, the rate of pathogenic alterations was 7.7% (n=1/13) in localized and 19.0% (n=4/21) in metastatic disease. When compared to NHW pts who underwent testing (n=139), the rate of pathogenic alterations was not significantly different (14.7% in Hispanic vs 12.2% in NWH, p=0.77). The rate of VUS in Hispanic pts was significantly higher than NHW pts (20.6% in Hispanic vs 7.2% in NWH, p=0.047). In a multivariate model examining the factors associated with receipt of testing in Hispanic men (Table), the presence of metastatic disease and a family history of PC were positively associated with testing. Spanish as a primary language was negatively associated with testing. Age was not a significant predictor. Conclusions: Among Hispanic men who underwent germline testing, there was a similar rate of pathogenic germline alterations compared to NHW men. Among Hispanic men, primary Spanish speakers appear to have lower rates of germline testing. Bilingual strategies are needed to improve rates of testing to ensure equity in germline testing for all patients. [Table: see text]

Biological features and clinical outcome in infant neuroblastoma: a multicenter experience in Beijing.

Neuroblastoma (NB) is the most common extracranial solid tumor in childhood, with 37% of patients diagnosed during infancy. This study is aimed at evaluating the survival outcome in infants diagnosed with neuroblastoma. This was a retrospective cohort study including patients under the age of 12 months with neuroblastoma from four tertiary referral centers in Beijing, China (Beijing Children's Hospital, Beijing Tongren Hospital, Peking University First Hospital, and Capital Institute of Pediatrics). Two hundred and forty-seven infants with neuroblastoma were included (male = 132 and female = 115). 91.1% (n = 225) patients were classified as having low-risk or intermediate-risk disease and 8.9% (n = 22) as having high-risk disease. The most common metastatic site is distant lymph node (n=89, 36.0%), followed by liver (n=57, 23.1%), bone (n=42, 17.0%), bone marrow (n=37, 15.0%), soft tissue (n=25, 10%), and central nervous system (n=4, 1.6%). MYCN amplification was present in 9.9% of tumor samples, chromosome 1p or 11q aberration in 14%. Treatment involved surgery alone in 9.7% of patients (n=24, all with low-risk disease), surgery followed by adjuvant chemotherapy in 50.2% (n=124), neoadjuvant chemotherapy followed by surgery in 40.1% (n=97), and chemotherapy alone in 0.8% (n=2). 4.9% (n=12) patients died, and the major cause of death is disease progression. Three-year event-free and overall survival were 91.6%±2.1% and 97.4%±1.1%, respectively, in patients with low- or intermediate-risk disease, and 58.7%±11.5% and 63.6%±11.2%, respectively, in those with high-risk disease.Conclusions: Infants with neuroblastoma achieve a reasonable clinical outcome when treated with surgery with or without chemotherapy using a risk-stratified approach in China. Such information will facilitate counseling, therapeutic decision-making, and development of adapted standard-of-care guidelines for future patients in the country. What is Known: • NB is a disease of infancy; 37% of patients are diagnosed as infants. • Most children younger than 12 months of age have a good prognosis even in the presence of metastatic disease. What is New: • Infants with neuroblastoma achieve reasonable clinical outcome when treated with surgery with or without chemotherapy using a risk-stratified approach in China. • CNS metastasis in infants with neuroblastoma is very rare at diagnosis and had a worse prognosis than those without metastasis.

Photodynamic Therapy Using Hippo Pathway Inhibitor Verteporfin: A Potential Dual Mechanistic Approach in Treatment of Soft Tissue Sarcomas.

Simple SummaryAdvanced sarcomas have yet to undergo improved outcomes seen in other cancer subtypes. Verteporfin has the potential to show landmark change in sarcoma due to its anti-proliferative properties: inhibition of the Hippo pathway and as photodynamic therapy. The effect of verteporfin on the Hippo pathway is reviewed specifically in the setting of sarcoma due to increased activation of this pathway in multiple subtypes. Role and efficacy of photodynamic therapy in other malignancies is also reviewed, with additional discussion of preclinical studies demonstrating synergistic effects of photodynamic therapy within current sarcoma standard of care treatment. Future investigations of the feasibility of incorporating verteporfin into sarcoma treatment are discussed.Sarcoma is a widely varied and devastating oncological subtype, with overall five-year survival of 65% that drops to 16% with the presence of metastatic disease at diagnosis. Standard of care for localized sarcomas is predicated on local control with wide-local resection and radiation therapy, or, less commonly, chemotherapy, depending on tumor subtype. Verteporfin has the potential to be incorporated into this standard of care due to its unique molecular properties: inhibition of the upregulated Hippo pathway that frequently drives soft tissue sarcoma and photodynamic therapy-mediated necrosis due to oxidative damage. The initial anti-proliferative effect of verteporfin is mediated via binding and dissociation of YAP/TEAD proteins from the nucleus, ultimately leading to decreased cell proliferation as demonstrated in multiple in vitro studies. This effect has the potential to be compounded with use of photodynamic therapy to directly induce cellular necrosis with use of a clinical laser. Photodynamic therapy has been incorporated into multiple malignancies and has the potential to be incorporated into sarcoma treatment.

Risk Assessment of Visceral Sarcomas: A Comparative Study of 2698 Cases from the SEER Database.

Soft tissue sarcomas arising in visceral organs are rare and lack validated tumor-staging protocols. Clinicopathologic features and clinical outcomes of 2698 visceral sarcomas identified in the Surveillance, Epidemiology, and End Results Program (SEER) database were compared with sarcomas arising in the extremities/trunk (n = 10,237) or retroperitoneum (n = 1067) using standard statistical techniques. Important prognostic criteria for visceral sarcomas, as in other anatomic sites, included tumor size, histologic grade, and presence of metastatic disease. After adjustment for pertinent confounding factors, visceral sarcomas showed cancer-specific survival rates similar to those arising in the retroperitoneum but had worse outcomes than sarcomas in the extremities/trunk. Therefore, the prognostic performance of two different staging algorithms for retroperitoneal sarcomas was evaluated for their use in staging sarcomas of visceral organs. The current AJCC 8th edition and the recently derived Vanderbilt system for staging retroperitoneal sarcoma both showed adequate discrimination, as assessed by multiple clinical concordance indices, and no evidence of miscalibration. Therefore, the authors concluded that previously validated staging systems for retroperitoneal sarcomas based on conventional prognostic factors (histologic grade, tumor size, and presence of metastatic disease) are applicable to visceral sarcomas and should be incorporated into the next edition of the AJCC Cancer Staging Manual.

Treatment of low-risk gestational trophoblastic neoplasia.

Low-risk gestational trophoblastic neoplasia (GTN), defined as FIGO/WHO score 0-6, is highly curable with an overall survival rate, which is approximately 100%. For most low-risk GTN patients, first-line single-agent chemotherapy with either methotrexate or actinomycin-D is recommended with overall complete human chorionic gonadotrophin (hCG) response rates of 60%-90% in mostly retrospective, non-randomised studies. The few randomised trials that exist are not appropriately powered or designed to define the optimal first-line treatment. Approximately 25%-30% of low-risk patients will develop resistance to initial single-agent chemotherapy with an increase in the FIGO score, a diagnosis of choriocarcinoma, higher pre-treatment hCG and the presence of metastatic disease being associated with an increase in the risk of resistance. The optimal treatment of patients scoring WHO 5 and 6 remains poorly defined given that approximately 70%-80% of these patients develop resistance to first-line single-agent chemotherapy, and there is an urgent need to refine the FIGO/WHO scoring system so that these patients can be identified for more intensive therapy from the outset. Despite this, almost all low-risk patients who experience treatment failure with first-line monotherapy will be cured with either sequential single-agent chemotherapy or multiagent chemotherapy with or without surgery. Given the associated increased short and longer-term toxicities associated with multi-agent chemotherapy, promising strategies to reduce the exposure of women to combination chemotherapy in low-risk disease have been investigated, including the use of carboplatin and immune check-point inhibitors. Further evaluation is required to define optimal patient selection, particularly with the use of immunotherapeutic agents given their significant increased costs and lack of longer-term safety data. Although there is a clear need to revise the FIGO/WHO (2000) scoring system, consistent international use of this is recommended to facilitate the comparison of data along with future focus in the development of international collaborative translational and clinical research, including randomised controlled trials.

Outcome and prognosis for canine appendicular osteosarcoma treated with stereotactic body radiation therapy in 123 dogs.

Canine appendicular osteosarcoma is commonly treated with limb amputation; however, limb-sparing options are frequently desired or necessary for a subset of patients. We evaluated 123 patients and 130 sites treated with stereotactic body radiation therapy (SBRT). Eighty-two out of 98 dogs (84%) had maximum lameness improvement at a median of 3 weeks for a median of 6 months duration. Histopathologic evaluation of available samples from amputation or necropsy revealed >80% tumor necrosis in 50% of limbs consistent with local disease control. Of evaluable patients, 41% fractured and 21% pursued an amputation after treatment. Fine needle aspirate (n=52) and needle core biopsy (n=28) did not result in increased fracture risk compared to those without tumor sampling (n=50). Median survival time (MST) was 233 days and time to first event was 143 days. Gross tumor volume and planned target volume were significantly inversely associated with survival and tumor location was significantly associated with survival. Dogs with salvage amputation had a significantly longer MST compared to those without (346 vs 202 days; P=.04). The presence of metastatic disease at the time of treatment in 15 dogs did not significantly impact survival time (200 vs 237 days without metastasis; P=.58). Skin side effects correlated significantly with dose with 33% of patients with acute grade 3 effects developing consequential late grade 3 effects. While SBRT improves lameness in most patients, further investigation is needed to identify candidates with minimal early fracture risk prior to initiating therapy.

The Current Management of Ampullary Cancer: A Survey among Healthcare Workers Worldwide

Purpose: Ampullary adenocarcinoma (AAC) is rare. Therefore, guidelines for the management of patients diagnosed with AAC are not available. To gain insight in the current daily practice of AAC worldwide, this international survey study was performed. Methods: Surgeons and medical oncologists (in training), whom were members of the Dutch Pancreatic Cancer Group (DPCG) or the International Study Group on Ampullary Cancer (ISGACA), or contributed to (peri)ampullary cancer research, were invited through email (January till March 2021). Participants were also approached trough their colleagues and online media platforms. Results: Overall, 57 (72%) surgeons and 22 (28%) oncologists completed the survey. Most respondents work in Europe (81%), and 90% work in a pancreas expertise cancer. When choosing treatment, 94% of the respondents take patients performance status and the presence of metastatic disease into consideration. Neoadjuvant treatment is considered by 20% and adjuvant therapy by 75% of the respondents, with 71% choosing for adjuvant chemotherapeutic treatment alone and 4% choosing for combined adjuvant chemoradiation therapy. The formation of multidisciplinary teams, improvement in surgical and local procedures, increased availability of chemotherapy, and knowledge on tumor biology were interpreted as improvements in the last five years. The necessity for international registries and randomized controlled trials on neoadjuvant and adjuvant chemo(radio)therapy were mentioned frequently. Conclusion: This study highlights the worldwide variation in the management of patients diagnosed with AAC, especially regarding neoadjuvant and/or adjuvant therapy. More data, including randomized controlled trials and international registries are needed to develop evidence-based guidelines for a more standardized surgical, and oncological management.

Sporadic vs. MEN-associated pancreatic neuroendocrine tumors: multi-institutional clinicopathologic comparison

Introduction: Clinicopathologic distinctions of Multiple Endocrine Neoplasia (MEN) associated Pancreatic Neuroendocrine Tumor (PNET) are not well established. We sought to improve surgical decision making in MEN-associated PNET. Method: We reviewed a multi-institutional international PNET database for patients with MEN-associated or sporadic PNET. Clinicopathological characteristics were compared. Overall(OS) and disease-free survival(DFS) were analyzed. Propensity score matching reduced bias based on tumor size, t-stage, and age. Results: 651 patients were included(45 MEN1, 606 sporadic). Patients with MEN were diagnosed at a younger age (46vs58 years,p< 0.01), and were more often female (60vs49%,p< 0.01), multifocal (71vs19%,p< 0.01) and higher t-stage (76vs55% stage 4,p=0.034). Lymph node involvement and the presence of metastasis were similar between groups. The rate of total pancreatectomy was 5x higher in the MEN cohort (16vs3%,p=0.004). Median follow-up was 46 months. Survival analysis did not show significant differences between groups. DFS was 126 months in the MEN cohort vs.198 months in the sporadic cohort, but these curves were not statistically different (Figure). After matching was performed, survival remained similar between cohorts (OS median was not reached in either cohort, DFS 126 (MEN) vs 198 (Sporadic) months, p>0.5. Matched patients did not demonstrate differences in lymph node positivity (28vs25%,p=0.913) or presence of metastatic disease (22vs13%,p=0.29). Conclusion: MEN-associated PNET occurs more frequently in younger, female patients, and is associated with multi-focality and high t-stage. Survival for patients with MEN-associated PNET is excellent. Consideration should be given to active surveillance and/or parenchymal-sparing surgical interventions to preserve pancreatic function given the indolence of this disease.

IMbrave 151: a randomized phase II trial of atezolizumab combined with bevacizumab and chemotherapy in patients with advanced biliary tract cancer.

Background:Biliary tract cancers (BTCs) are heterogenous, highly aggressive tumors that harbor a dismal prognosis for which more effective treatments are needed. The role of cancer immunotherapy in BTC remains to be characterized. The tumor microenvironment (TME) of BTC is highly immunosuppressed and combination treatments are needed to promote effective anticancer immunity. Vascular endothelial growth factor (VEGF) drives immunosuppression in the TME by disrupting antigen presentation, limiting T-cell infiltration, or potentiating immune-suppressive cells. Many VEGF-regulated mechanisms are thought to be relevant to repressed antitumor immunity in BTC, making dual targeting of VEGF and programmed cell death protein 1 (PD-1)/PD-L1 pathways a rational approach. Gemcitabine and Cisplatin (Gem/Cis) can also modulate anticancer immunity through overlapping and complementary mechanisms to those regulated by VEGF. Anti-PD-L1/VEGF inhibition, coupled with chemotherapy, may potentiate antitumor immunity leading to enhanced clinical benefit.Methods:IMbrave 151 is a randomized, double-blind, placebo-controlled, multicenter, international phase II study to evaluate atezolizumab (a PD-L1 inhibitor) in combination with chemotherapy (gemcitabine and cisplatin) and bevacizumab (an anti-VEGF monoclonal antibody) as a first-line treatment for advanced BTC. Approximately 150 patients with previously untreated, advanced BTC will be randomized to either Arm A (atezolizumab + bevacizumab + Gem/Cis) or Arm B (atezolizumab + placebo + Gem/Cis). Randomization is stratified by the presence of metastatic disease, primary tumor location, and geographic region. The primary efficacy endpoint is investigator-assessed progression-free survival (PFS) per RECIST 1.1. Secondary endpoints include objective response rate (ORR), duration of response (DoR), disease control rate (DCR), overall survival (OS), and safety and patient reported outcomes (PROs). Tissue, blood, and stool samples will be collected at baseline and on-treatment in order to perform correlative biomarker analyses.Discussion:IMbrave 151 represents the first randomized study to evaluate combined PD-L1/VEGF blockade on a chemotherapy backbone in BTC.Trial registration:NCT identifier: NCT04677504; EUDRACT number: 2020-003759-14

A Population-based Study on Incidence, Treatment and Survival in Ampullary Cancer in the Netherlands

Purpose: Ampullary cancer is rare and as result the epidemiological data are scarce. The aim of this population-based study was to determine the trends in incidence, treatment and overall survival (OS) in patients with ampullary adenocarcinoma in the Netherlands between 1989 and 2016. Methods: Patients diagnosed with ampullary adenocarcinoma were identified from the Netherlands Cancer Registry. Incidence rates were age-adjusted to the European standard population. Trends in treatment and OS were studied over 7 years period of diagnosis, using Kaplan-Meier and Cox regression analyses for OS and stratified by the presence of metastatic disease. Results: In total, 3840 patients with ampullary adenocarcinoma were diagnosed of whom, 55.0% were male and 87.1% had non-metastatic disease. The incidence increased from 0.59 per 100,000 in 1989-1995 to 0.68 per 100,000in 2010-2016. In non-metastatic disease, the resection rate increased from 49.5% in 1989-1995 to 63.9% in 2010-2016 (p<0.001). The rate of adjuvant therapy increased from 3.1% to 7.9%. In non-metastatic disease, five-year OS (95% CI) increased from 19.8% (16.9-22.8) in 1989-1995 to 29.1% (26.0-31.2) in 2010-2016 (logrank p<0.001). In patients with metastatic disease, median OS did improve, but not significantly (from 4.4 months (3.6-5.0) to 5.9 months (4.7-7.1); logrank p=0.06). Cancer treatment was an independent prognostic factor for OS among all patients. Conclusion: Both incidence and OS of ampullary cancer increased from 1989 to 2016, which is likely related to the observed increased resection rates and use of adjuvant therapy as well as better diagnostics and centralization of pancreatic surgeries.

Melphalan, Etoposide, and Carboplatin Megatherapy with Autologous Stem Cell Transplantation in Children with Relapsing or Therapy-Resistant Extracranial Germ-Cell Tumors-A Retrospective Analysis.

Simple SummaryGerm cell tumors (GCTs) are malignancies derived from germ cells that originate in gonads or extragonadal localizations. They are considered highly curable in both children and adults even if distant metastases are present, but therapy-resistant or relapsing patients have a worse prognosis. The aim of our retrospective study was to analyze the outcome of 18 children with GCT treated with melphalan–etoposide–carboplatin high-dose chemotherapy and autologous stem cell transplantation. To date, this is one of the largest reported pediatric cohorts of GCT patients treated with megatherapy. We observed high survival rates—a five-year overall survival of 76%, and event-free survival of 70.8% without therapy-associated mortality. We concluded that this megatherapy protocol is feasible in heavily pretreated children, but the issue of precise indications for high dose chemotherapy (HDCT) is evident and must be answered in a well-designed controlled study to avoid unnecessary overtreatment.Pediatric germ cell tumors (GCTs) are a group of chemosensitive malignancies with a 90% curability rate. We report a series of children with relapsing or therapy-resistant GCT treated with melphalan–etoposide–carboplatin high-dose chemotherapy (HDCT) and autologous stem cell transplantation. This consisted of 18 children, either with GCTs after relapse (nine patients) or with an unsatisfactory response to first-line chemotherapy (nine patients), who underwent HDCT. The HDCT regimens MEC1 (carboplatin 1500 mg/m2, etoposide 1800 mg/m2, and melphalan 140 mg/m2) and MEC2 (carboplatin 800 mg/m2, etoposide 800 mg/m2, and melphalan 140 mg/m2) were each used in nine patients. The median observation time was 81 months, the 5-year overall survival (OS) was 76%, and the event-free survival (EFS) was 70.8%. Non-relapse mortality was 0%, and four patients died after HDCT due to progression of the malignancy. No difference in OS or EFS was noted between the MEC1 and MEC2 protocols. The 5-year OS and 5-year EFS were higher in children treated with autologous stem cell transplantation before the age of four years. The presence of metastatic disease or time of HDCT consolidation during first/subsequent line chemotherapy did not affect patient survival. The melphalan–etoposide–carboplatin protocol is feasible in pediatric GCT, but is associated with potentially life-threatening complications. In conclusion, the use of HDCT must be examined in well-designed clinical trials, and the identification of patients who can benefit from this approach is critical to avoid overtreatment.

Factors and Survival Implications associated with biopsy of hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is one of the few cancers that can be diagnosed based on imaging findings alone. The factors associated with the decision to perform a biopsy and the clinical impact have not been previously studied. MethodsWe collected data of patients diagnosed with HCC between 2004 and 2015 from the National Cancer Database. We assessed associations between biopsy and survival with demographic and clinical factors. ResultsWe included 160,507 patients. The median age was 62 (40–90), 74.1% were male and 74.9% were white. Over the 12-year period, 47.7% (76,524/160,517) underwent a biopsy. Factors associated with a biopsy were black race, older age, presence of metastatic disease, larger tumor size, and treatment at a community cancer center. Factors associated with increased mortality were older age, higher comorbidity index, larger tumor size, presence of metastatic disease, higher AFP and elevated bilirubin. There was a significant decreased use of biopsy over successive years (2007–2015). After adjusting for prognostic factors, biopsy had no significant impact on survival HR 1.01 (95%CI 1.00–1.03. p = 0.07). ConclusionsA significant number of patients underwent a biopsy. Performing a biopsy did not have a significant impact on survival.

Upfront Small Bowel Resection for Small Bowel Neuroendocrine Tumors With Synchronous Metastases: A Propensity-score Matched Comparative Population-based Analysis.

We examined the impact of upfront small bowel resection (USBR) for metastatic small bowel neuroendocrine (SB-NET) compared to nonoperative management (NOM) on long-term healthcare utilization and survival outcomes. The role of early resection of the primary tumor in metastatic SB-NET remains controversial. Conflicting data exist regarding its clinical and survival benefits. This is a population-based retrospective matched comparative cohort study of adults diagnosed with synchronous metastatic SB-NET between 2001 and 2017 in Ontario. USBR was defined as resection within 6 months of diagnosis. Primary outcomes were subsequent unplanned acute care admissions and small bowel-related surgery. Secondary outcome was overall survival. USBR and NOM patients were matched 2:1 using a propensity-score. We used time-to-event analyses with cumulative incidencefunctions and univariate Andersen-Gill regression for primary outcomes. E value methods assessed the potential for residual confounding. Of 1000 patients identified, 785 had USBR. The matched cohort included 348 patients with USBR and 174 with NOM. Patients with USBR had lower 3-year risk of subsequent admissions (72.6% vs 86.4%, P < 0.001) than those with NOM, with hazard ratio 0.72 (95% confidence interval 0.570.91). USBR was associated with lower risk of subsequent small bowel-related surgery (15.4% vs 40.3%, P < 0.001), with hazard ratio 0.44 (95% confidence interval 0.29-0.67). E -values indicated it was unlikely that the observed risk estimates could be explained by an unmeasured confounder. Sensitivity analysis excluding emergent resections to define USBR did not alter the results. USBR for SB-NETs in the presence of metastatic disease was associated with better patient-oriented outcomes of decreased subsequent admissions and interventions, compared to NOM. USBR should be considered for metastatic SB-NETs.

Pediatric hepatic cancer incidence and survival: 30-year trends in Ontario, Canada; the United States; and Australia.

Pediatric hepatic cancer is a rare malignancy, comprising only approximately 2% of all cancers diagnosed in children aged <15 years. The authors sought to describe trends in pediatric hepatic cancer incidence and survival in Ontario, Canada; the United States; and Australia. Children aged <15 years who were diagnosed with hepatic cancer from 1985 through 2013 were ascertained through population-based registries and followed from the time of diagnosis until December 31, 2015. Age-standardized incidence and 5-year relative survival were calculated for each jurisdiction. Multivariable flexible parametric survival models were used to explore predictors of hepatic cancer mortality. A total of 794 children were identified in Ontario (148 children), the United States (400 children), and Australia (246 children). The average annual incidence increased by 2.2% (95% CI, 0.5%-4.0%) in Australia, 2.1% (95% CI, 0.9%-3.3%) in the United States, and 1.3% (95% CI, -0.4% to 3.0%) in Ontario. The 5-year relative survival rate improved from 60% to 82% (P = .08) in Ontario and 62% to 78% (P = .02) in the United States between the diagnostic periods 1985 through 1994 and 2005 through 2013, whereas in Australia the rate remained constant (between 74% and 77%) during the study period. On multivariable analysis, there was no significant difference noted with regard to the hazard of death between jurisdictions (P = .06). Older age, the presence of metastatic disease, and being diagnosed with hepatocellular carcinoma were found to be associated with mortality. The incidence of hepatic cancer in children appears to have increased over the last 30 years in Australia and North America. Survival differences between Australia; Ontario, Canada; and the United States observed in the 1980s and 1990s were no longer apparent and only marginal geographical differences in the hazard of mortality were observed.

Malnutrition Prevalence according to the GLIM Criteria in Head and Neck Cancer Patients Undergoing Cancer Treatment.

Malnutrition is highly prevalent in people with head and neck cancer (HCN) and is associated with poorer outcomes. However, variation in malnutrition diagnostic criteria has made translation of the most effective interventions into practice challenging. This study aimed to determine the prevalence of malnutrition in a HNC population according to the Global Leadership Initiative on Malnutrition (GLIM) criteria and assess inter-rater reliability and predictive validity. A secondary analysis of data available for 188 patients with HNC extracted from two cancer malnutrition point prevalence studies was conducted. A GLIM diagnosis of malnutrition was assigned when one phenotypic and one etiologic criterion were present. Phenotypic criteria were ≥5% unintentional loss of body weight, body mass index (BMI), and subjective evidence of muscle loss. Etiologic criteria were reduced food intake, and presence of metastatic disease as a proxy for inflammation. The prevalence of malnutrition was 22.6% (8.0% moderately malnourished; 13.3% severely malnourished). Inter-rater reliability was classified as excellent for the GLIM criteria overall, as well as for each individual criterion. A GLIM diagnosis of malnutrition was found to be significantly associated with BMI but was not predictive of 30 day hospital readmission. Further large, prospective cohort studies are required in this patient population to further validate the GLIM criteria.