scholarly journals Ewing Sarcoma—Diagnosis, Treatment, Clinical Challenges and Future Perspectives

2021 ◽  
Vol 10 (8) ◽  
pp. 1685
Author(s):  
Stefan K. Zöllner ◽  
James F. Amatruda ◽  
Sebastian Bauer ◽  
Stéphane Collaud ◽  
Enrique de Álava ◽  
...  
Keyword(s):  
Ewing Sarcoma ◽  
Local Treatment ◽  
Standard Of Care ◽  
Current Standard ◽  
Potential Therapeutic Target ◽  
Dismal Prognosis ◽  
Physical Burden ◽  
International Collaborations ◽  
Multiple Cycles ◽  
Tissue Cancer

Ewing sarcoma, a highly aggressive bone and soft-tissue cancer, is considered a prime example of the paradigms of a translocation-positive sarcoma: a genetically rather simple disease with a specific and neomorphic-potential therapeutic target, whose oncogenic role was irrefutably defined decades ago. This is a disease that by definition has micrometastatic disease at diagnosis and a dismal prognosis for patients with macrometastatic or recurrent disease. International collaborations have defined the current standard of care in prospective studies, delivering multiple cycles of systemic therapy combined with local treatment; both are associated with significant morbidity that may result in strong psychological and physical burden for survivors. Nevertheless, the combination of non-directed chemotherapeutics and ever-evolving local modalities nowadays achieve a realistic chance of cure for the majority of patients with Ewing sarcoma. In this review, we focus on the current standard of diagnosis and treatment while attempting to answer some of the most pressing questions in clinical practice. In addition, this review provides scientific answers to clinical phenomena and occasionally defines the resulting translational studies needed to overcome the hurdle of treatment-associated morbidities and, most importantly, non-survival.

scholarly journals Response to Immunotherapy in Combination With Mitotane in Patients With Metastatic Adrenocortical Cancer

2019 ◽  
Vol 3 (12) ◽  
pp. 2295-2304 ◽  
Author(s):  
Lia Head ◽  
Katja Kiseljak-Vassiliades ◽  
Toshimasa J Clark ◽  
Hilary Somerset ◽  
Jonathan King ◽  
...  
Keyword(s):  
Evaluation Criteria ◽  
Standard Of Care ◽  
Response Evaluation ◽  
Adrenocortical Cancer ◽  
First Line ◽  
Current Standard ◽  
Dismal Prognosis ◽  
Grade 3 ◽  
Combined Immunotherapy ◽  
First Line Treatment

Abstract Adrenocortical carcinoma (ACC) is a rare orphan disease with a dismal prognosis. Surgery remains the first-line treatment, but most patients eventually develop metastatic disease. Mitotane is often used with chemotherapy with modest success. Little information is available concerning the efficacy of immunotherapy in combination with mitotane. We conducted a retrospective review of our initial six patients with metastatic ACC, for whom mitotane alone or with chemotherapy failed, and who were subsequently treated with a combination of pembrolizumab and mitotane, between July 2016 and March 2019. Imaging was analyzed per Response Evaluation Criteria in Solid Tumours 1.1 criteria. Two patients had a partial response and four patients had stable disease (8 to 19 months). One patient had grade 3 hepatitis and pembrolizumab was discontinued after 8 months. She died with disease progression 16 months after initiating pembrolizumab. One patient developed brain metastasis after 19 months of treatment and was transitioned to hospice. One patient had focal pneumonitis after 18 months of treatment, and pembrolizumab was discontinued. Three remaining patients continue pembrolizumab plus mitotane at the time of this writing. The current standard of care for ACC is a combination of etoposide, doxorubicin, cisplatin, and mitotane with an overall survival of 14.8 months. All six patients lived for at least 16 months after starting pembrolizumab added to mitotane therapy. The therapy appeared to be effective in both microsatellite instability-high and microsatellite stable tumors, suggesting some synergistic effect with mitotane. Combined immunotherapy and mitotane should be considered in future clinical trials in patients with ACC.

scholarly journals Rationale and Clinical Implications of Fluorescein-Guided Supramarginal Resection in Newly Diagnosed High-Grade Glioma

2021 ◽  
Vol 11 ◽  
Author(s):  
Linda M. Wang ◽  
Matei A. Banu ◽  
Peter Canoll ◽  
Jeffrey N. Bruce
Keyword(s):  
Overall Survival ◽  
Surgical Resection ◽  
Local Treatment ◽  
Standard Of Care ◽  
High Grade Glioma ◽  
Extent Of Resection ◽  
Brain Parenchyma ◽  
Clinical Implications ◽  
Current Standard ◽  
Supramarginal Resection

Current standard of care for glioblastoma is surgical resection followed by temozolomide chemotherapy and radiation. Recent studies have demonstrated that >95% extent of resection is associated with better outcomes, including prolonged progression-free and overall survival. The diffusely infiltrative pattern of growth in gliomas results in microscopic extension of tumor cells into surrounding brain parenchyma that makes complete resection unattainable. The historical goal of surgical management has therefore been maximal safe resection, traditionally guided by MRI and defined as removal of all contrast-enhancing tumor. Optimization of surgical resection has led to the concept of supramarginal resection, or removal beyond the contrast-enhancing region on MRI. This strategy of extending the cytoreductive goal targets a tumor region thought to be important in the recurrence or progression of disease as well as resistance to systemic and local treatment. This approach must be balanced against the risk of impacting eloquent regions of brain and causing permanent neurologic deficit, an important factor affecting overall survival. Over the years, fluorescent agents such as fluorescein sodium have been explored as a means of more reliably delineating the boundary between tumor core, tumor-infiltrated brain, and surrounding cortex. Here we examine the rationale behind extending resection into the infiltrative tumor margins, review the current literature surrounding the use of fluorescein in supramarginal resection of gliomas, discuss the experience of our own institution in utilizing fluorescein to maximize glioma extent of resection, and assess the clinical implications of this treatment strategy.

scholarly journals A Review of Newly Diagnosed Glioblastoma

2021 ◽  
Vol 10 ◽  
Author(s):  
Bryan Oronsky ◽  
Tony R. Reid ◽  
Arnold Oronsky ◽  
Navjot Sandhu ◽  
Susan J. Knox
Keyword(s):  
Brain Tumor ◽  
Surgical Resection ◽  
Standard Of Care ◽  
Newly Diagnosed ◽  
Current Standard ◽  
Genetic Characteristics ◽  
Dismal Prognosis ◽  
Newly Diagnosed Glioblastoma ◽  
Temozolomide Chemotherapy

Glioblastoma is an aggressive and inevitably recurrent primary intra-axial brain tumor with a dismal prognosis. The current mainstay of treatment involves maximally safe surgical resection followed by radiotherapy over a 6-week period with concomitant temozolomide chemotherapy followed by temozolomide maintenance. This review provides a summary of the epidemiological, clinical, histologic and genetic characteristics of newly diagnosed disease as well as the current standard of care and potential future therapeutic prospects.

The treatment results in patients with Ewing Sarcoma: The Polish Sarcoma Group Experience.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e23503-e23503
Author(s):  
Iwona Lugowska ◽  
Paulina Jagodzinska-Mucha ◽  
Anna Raciborska ◽  
Katarzyna Bilska ◽  
Hanna Kosela-Paterczyk ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Ewing Sarcoma ◽  
Cox Model ◽  
Bone Marrow Involvement ◽  
Local Treatment ◽  
Standard Of Care ◽  
Rank Test ◽  
Treatment Results ◽  
Rare Type ◽  
Cox Analysis

e23503 Background: Ewing Sarcoma is a rare type of aggressive tumor that occurs in bones or in the soft tissue around the bones. The multidisciplinary approach chemotherapy (CHT), radiotherapy (RTH) and surgery (S) is the standard of care. The aim of our study was to analyze prognostic factors and treatment results in patients with Ewing Sarcoma. Methods: 504 patient with Ewing sarcoma treated between 1998 and 2019, F:M 1:1.34, with metastases at presentation was 195 patients (39%), axial localization was in 277 patients (55%). All patient were treated with multimodal treatment based on chemotherapy, radiotherapy and surgery. Kaplan-Meier estimator, log rank test and multivariate Cox model were used for statistical analysis. Results: Five year overall survival (5y-OS) was 54% (CI:49-60%), prognostic factors were: gender (5y-OS for females and males equal to 63% and 48%, respectively), age (5y-OS stratified patients between < 10y; 10-15y; 15-25 and 25+ was 65%, 70%, 41% and 55%;p < 0.001), metastases (5y-OS in group with M1 was 31% and in M0 - 70%; p < 0.001), type of local treatment (5y-OS in group CHT/S/RTH was 61%, CHT/S 59%, only RTH 50% and palliative treatment without local treatment equals 12%; p < 0.001). Multivariate Cox analysis revealed death hazard dependence on gender (male vs. female; HR = 1.80; p < 0.01), metastatic status (M1 vs. M0; HR = 2.91; p < 0.001), bone/bone marrow involvement (present vs. absent; HR = 2.10; p < 0.01) and chemotherapy regime (other vs. VIDE/VAI; HR = 0.69; p = 0.049). Conclusions: The treatment results in Ewing sarcoma are significantly better in children than in adults, which can be related to the more intensive chemotherapy regiments applied. The treatment should be provided in referral centers and based on up-to-dated guideline.

scholarly journals Sphingolipid Metabolism in Glioblastoma and Metastatic Brain Tumors: A Review of Sphingomyelinases and Sphingosine-1-Phosphate

Biomolecules ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1357
Author(s):  
Cyntanna C. Hawkins ◽  
Tomader Ali ◽  
Sasanka Ramanadham ◽  
Anita B. Hjelmeland
Keyword(s):  
Brain Tumors ◽  
Biological Effects ◽  
Standard Of Care ◽  
Sphingolipid Metabolism ◽  
Metastatic Brain Tumors ◽  
Current Standard ◽  
Adaptive Immune Cells ◽  
Dismal Prognosis ◽  
Wide Range ◽  
Sphingosine 1 Phosphate

Glioblastoma (GBM) is a primary malignant brain tumor with a dismal prognosis, partially due to our inability to completely remove and kill all GBM cells. Rapid tumor recurrence contributes to a median survival of only 15 months with the current standard of care which includes maximal surgical resection, radiation, and temozolomide (TMZ), a blood–brain barrier (BBB) penetrant chemotherapy. Radiation and TMZ cause sphingomyelinases (SMase) to hydrolyze sphingomyelins to generate ceramides, which induce apoptosis. However, cells can evade apoptosis by converting ceramides to sphingosine-1-phosphate (S1P). S1P has been implicated in a wide range of cancers including GBM. Upregulation of S1P has been linked to the proliferation and invasion of GBM and other cancers that display a propensity for brain metastasis. To mediate their biological effects, SMases and S1P modulate signaling via phospholipase C (PLC) and phospholipase D (PLD). In addition, both SMase and S1P may alter the integrity of the BBB leading to infiltration of tumor-promoting immune populations. SMase activity has been associated with tumor evasion of the immune system, while S1P creates a gradient for trafficking of innate and adaptive immune cells. This review will explore the role of sphingolipid metabolism and pharmacological interventions in GBM and metastatic brain tumors with a focus on SMase and S1P.

scholarly journals Endoscopic Ultrasound-Guided Intratumoural Therapy for Pancreatic Cancer

2008 ◽  
Vol 22 (4) ◽  
pp. 405-410 ◽  
Author(s):  
Brian M Yan ◽  
Jacques Van Dam
Keyword(s):  
Pancreatic Cancer ◽  
Endoscopic Ultrasound ◽  
Standard Of Care ◽  
Current Standard ◽  
Interventional Eus ◽  
Therapeutic Modalities ◽  
Dismal Prognosis ◽  
Ablative Techniques ◽  
Fine Needle Injection ◽  
Pancreatic Cancer Therapy

Pancreatic cancer is the second most frequent gastrointestinal malignancy and carries a dismal prognosis. The current standard of care includes resection, if possible, as well as systemic chemoradiation therapy. Endoscopic ultrasound (EUS) is an established technique for the diagnosis and staging of pancreatic adenocarcinoma. Interventional EUS via fine needle injection (FNI) for the treatment of pancreatic cancer is a rapidly expanding field. The present article reviews the up-to-date developments in EUS FNI for intratumoural pancreatic cancer therapy, including antitumoural agents, immunotherapy, ablative techniques and new delivery systems. The therapeutic modalities discussed are currently under development and will hopefully reach clinical practice if benefit is demonstrated through clinical trials. EUS FNI may be an exciting new technique for the delivery of desperately needed novel therapies for pancreatic cancer.

scholarly journals Effect of cisplatin-based neoadjuvant chemotherapy on survival in patients with bladder cancer: a meta-analysis

2017 ◽  
Vol 40 (2) ◽  
pp. 81 ◽  
Author(s):  
Gang Li ◽  
Hui-min Niu ◽  
Hong-tao Wu ◽  
Bao-yu Lei ◽  
Xiao-hua Wang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Meta Analysis ◽  
Local Treatment ◽  
Final Analysis ◽  
Standard Of Care ◽  
Current Standard ◽  
Pubmed Central ◽  
Similar Survival ◽  
Muscle Invasive

Purpose: Cisplatin-based neoadjuvant chemotherapy (NAC) has been shown to improve survival in patients with muscle-invasive bladder cancer (MIBC) who underwent radical cystectomy as compared with patients who underwent surgery alone. It has also been suggested as current standard of care in surgically-fit patients with MIBC. This meta-analysis assessed the effect of cisplatin-based NAC on survival in patients with bladder cancer. Source: PubMed, CENTRAL, and Embase were searched until November 22, 2016. Two-arm randomized controlled trials that compared cisplatin-based neoadjuvant chemotherapy plus local treatment versus the same local treatment without neoadjuvant chemotherapy were selected. Patients with histologically-confirmed bladder cancer (adenocarcinoma, transitional, or squamous-cell carcinoma) were included. The primary outcome was overall survival (OS). Principal findings: Of the 292 articles initially identified, 14 were included in the final analysis. Patients in the NAC group had similar OS as the local treatment (i.e., radiation therapy or cystectomy) group (pooled hazard ratio [HR] = 0.92, 95% confidence interval [CI]: 0.84 to 1.00, P=0.056). No difference in progress-free survival between two groups was observed (P=0.725). Subgroup analysis showed that OS was similar in patients treated with NAC plus radiotherapy or cystectomy compared with patients who received local treatment alone. Conclusions: Platinum-based NAC was associated with similar survival benefit as patients undergoing cystectomy and/or radiotherapy. No conclusion can be drawn about the optimal platinum-based combination to be used in the neoadjuvant setting.

Acute Rejection Following Kidney Transplantation: State-of-the-Art and Future Perspectives

2020 ◽  
Vol 26 (28) ◽  
pp. 3468-3496
Author(s):  
Emilio Rodrigo ◽  
Marcio F. Chedid ◽  
David San Segundo ◽  
Juan C.R. San Millán ◽  
Marcos López-Hoyos
Keyword(s):  
Kidney Transplantation ◽  
Acute Rejection ◽  
Rescue Therapy ◽  
Standard Of Care ◽  
Rejection Rate ◽  
New Drugs ◽  
High Dose ◽  
Current Standard ◽  
Antibody Mediated Rejection ◽  
Cellular Rejection

: Although acute renal graft rejection rate has declined in the last years, and because an adequate therapy can improve graft outcome, its therapy remains as one of the most significant challenges for pharmacists and physicians taking care of transplant patients. Due to the lack of evidence highlighted by the available metaanalyses, we performed a narrative review focused on the basic mechanisms and current and future therapies of acute rejection in kidney transplantation. : According to Kidney Disease/Improving Global Outcomes (KDIGO) guidelines, both clinical and subclinical acute rejection episodes should be treated. Usually, high dose steroids and basal immunosuppression optimization are the first line of therapy in treating acute cellular rejection. Rabbit antithymocytic polyclonal globulins are used as rescue therapy for recurrent or steroid-resistant cellular rejection episodes. Current standard-of-care (SOC) therapy for acute antibody-mediated rejection (AbMR) is the combination of plasma exchange with intravenous immunoglobulin (IVIG). Since a significant rate of AbMR does not respond to SOC, different studies have analyzed the role of new drugs such as Rituximab, Bortezomib, Eculizumab and C1 inhibitors. Lack of randomized controlled trials and heterogenicity among performed studies limit obtaining definite conclusions. Data about new direct and indirect B cell and plasma cell depleting agents, proximal and terminal complement blockers, IL-6/IL-6R pathway inhibitors and antibody removal agents, among other promising drugs, are reviewed.

scholarly journals Inhibition of Glycine Re-Uptake: A Potential Approach for Treating Pain by Augmenting Glycine-Mediated Spinal Neurotransmission and Blunting Central Nociceptive Signaling

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 864
Author(s):  
Christopher L. Cioffi
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Therapeutic Potential ◽  
Opioid Analgesic ◽  
Critical Role ◽  
Analgesic Efficacy ◽  
Standard Of Care ◽  
Current Standard ◽  
Glycine Transporters ◽  
Pathological Pain

Among the myriad of cellular and molecular processes identified as contributing to pathological pain, disinhibition of spinal cord nociceptive signaling to higher cortical centers plays a critical role. Importantly, evidence suggests that impaired glycinergic neurotransmission develops in the dorsal horn of the spinal cord in inflammatory and neuropathic pain models and is a key maladaptive mechanism causing mechanical hyperalgesia and allodynia. Thus, it has been hypothesized that pharmacological agents capable of augmenting glycinergic tone within the dorsal horn may be able to blunt or block aberrant nociceptor signaling to the brain and serve as a novel class of analgesics for various pathological pain states. Indeed, drugs that enhance dysfunctional glycinergic transmission, and in particular inhibitors of the glycine transporters (GlyT1 and GlyT2), are generating widespread interest as a potential class of novel analgesics. The GlyTs are Na+/Cl−-dependent transporters of the solute carrier 6 (SLC6) family and it has been proposed that the inhibition of them presents a possible mechanism by which to increase spinal extracellular glycine concentrations and enhance GlyR-mediated inhibitory neurotransmission in the dorsal horn. Various inhibitors of both GlyT1 and GlyT2 have demonstrated broad analgesic efficacy in several preclinical models of acute and chronic pain, providing promise for the approach to deliver a first-in-class non-opioid analgesic with a mechanism of action differentiated from current standard of care. This review will highlight the therapeutic potential of GlyT inhibitors as a novel class of analgesics, present recent advances reported for the field, and discuss the key challenges associated with the development of a GlyT inhibitor into a safe and effective agent to treat pain.

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