scholarly journals Moving Beyond Gleason Scoring

2019 ◽  
Vol 143 (5) ◽  
pp. 565-570 ◽  
Author(s):  
Brian Miles ◽  
Michael Ittmann ◽  
Thomas Wheeler ◽  
Mohammad Sayeeduddin ◽  
Antonio Cubilla ◽  
...  
Keyword(s):  
Biochemical Recurrence ◽  
Host Response ◽  
Cancer Survival ◽  
Predictive Ability ◽  
Standard Of Care ◽  
Molecular Data ◽  
Current Standard ◽  
Reactive Stroma ◽  
Response Measures ◽  
Definition Of

Context.— The combination of grading and staging is the basis of current standard of care for prediction for most cancers. D. F. Gleason created the current prostate cancer (PCa) grading system. This system has been modified several times. Molecular data have been added. Currently, all grading systems are cancer-cell based. Objective.— To review the literature available on host response measures as reactive stroma grading and stromogenic carcinoma, and their predictive ability for PCa biochemical recurrence and PCa-specific death. Data Sources.— Our own experience has shown that reactive stroma grading and the subsequently binarized system (stromogenic carcinoma) can independently predict biochemical recurrence and/or PCa-specific death, particularly in patients with a Gleason score of 6 or 7. Stromogenic carcinoma has been validated by 4 other independent groups in at least 3 continents. Conclusions.— Broders grading and Dukes staging have been combined to form the most powerful prognostic tools in standard of care. The time has come for us to incorporate measures of host response (stromogenic carcinoma) into the arsenal of elements we use to predict cancer survival, without abandoning what we know works. These data also suggest that our current definition of PCa might need some revision.

Similar Incidence of Typhlitis in Patients Receiving Various Doses of Daunorubicin or Idarubicin As Induction for Acute Myeloid Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3725-3725
Author(s):  
Amanda N Seddon ◽  
Angela G Michael ◽  
Nelly G. Adel ◽  
Martin S. Tallman ◽  
Oguz Akin ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Conflicts Of Interest ◽  
Standard Of Care ◽  
Adult Patients ◽  
Cell Transplant ◽  
Current Standard ◽  
Ileocecal Region ◽  
Concomitant Infection ◽  
Potential Factors ◽  
Definition Of

Abstract Background: The current standard of care for the treatment of patients with newly diagnosed AML is an anthracycline plus cytarabine. Both anthracyclines and cytarabine have been associated with the development of typhlitis, a serious adverse event characterized by inflammation of the bowel wall in patients with profound neutropenia, diagnosed via abdominal CT imaging and clinical symptoms. Given the paucity of available data, the aim of our study was to determine the incidence of typhlitis among AML patients receiving induction with either idarubicin 12 mg/m2 (IDA), daunorubicin 60 mg/m2 (DNA60), or daunorubicin 90 mg/m2 (DNA90). Methods: Adult patients with AML or MDS receiving either daunorubicin or idarubicin along with cytarabine as part of their induction regimen between 1/1/2009 and 6/30/2013 were included. A definition of typhlitis required CT confirmation of inflammation of the cecum, according to CTCAE version 4.03 along with clinical symptoms. Two radiologists (OA, JC) blinded to the treatment and outcomes independently reviewed CT scans. Two additional definitions including inflammation of the ileocecal region only and enterocolitis were also evaluated. All statistical analyses were performed on SAS software version 9.3. P values were calculated using Fisher Exact and Wilcoxon tests. Inter-rater reliability was assessed with Cohen’s Kappa. Results: Baseline characteristics were similar among the 3 treatment groups with the exception of age. The median age was lower in the DNA90 arm (79 years, 74 years, and 49 years in the IDA group, DNA60 group, and DNA90 group, respectively). A pre-existing GI disorder was reported in 24.1% IDA, 25.7% DNA60, and 22.4% DNA90 patients. Of the 202 total patients, the two radiologists determined that 40 (20%) and 38 (19%) developed typhlitis, based on the predefined standard. Tables 1 and 2 illustrate the relationship between treatment arm and associated incidence of typhlitis. The incidence in each treatment group did not statistically differ (p=0.23 and p=0.29). When the definition was broadened to include ileocecal region and enterocolitis, the incidence increased (Tables 1 and 2). The inter-reliability ratings of the 2 radiologists’ evaluations for each definition indicated substantial agreement (0.803 cecum, 0.834 ileocecal region only, and 0.752 enterocolitis). Neither the anthracycline chosen, nor the dose had a statistically significant impact on the incidence of typhlitis. Of all patient and treatment specific risk factors assessed for association with development of typhlitis (pre-existing GI disorder, rheumatologic disorder or cancer, prior RT, stem cell transplant or anthracycline exposure, cytarabine regimen or AML risk group), none were found to be statistically significant. In patients that developed typhlitis, approximately 56% and 51% had a concurrent documented infection around the typhlitis episode (Tables 1-2). Conclusion: To our knowledge, this is the first study to compare the incidence of typhlitis in adult patients receiving idarubicin or daunorubicin for the treatment of AML. While the cumulative incidence of typhlitis was higher than in published literature, the incidence was similar irrespective of the anthracycline chosen or dose. Of the potential factors that may have contributed to the development of typhlitis, none were significantly associated with typhlitis. All patients were managed conservatively with broad-spectrum antibiotics. A more definitive definition of typhlitis may help clinicians identify affected patients sooner and choose appropriate targeted therapy. Abstract 3725. Table 1. Association of treatment to Radiologist 1-rated typhlitis Enterocolitis Ileocecal region only Cecum No Yes P No Yes P No Yes P Treatment 0.52 0.68 0.23 DNA60 58 (78%) 16 (22%) 58 (78%) 16 (22%) 61 (82%) 13 (18%) DNA90 34 (69%) 15 (31%) 35 (71%) 14 (29%) 35 (71%) 14 (29%) IDA 58 (73%) 21 (27%) 60 (76%) 19 (24%) 66 (84%) 13 (16%) Concomitant infection Yes 11 (26%) 32 (74%) 13 (30%) 30 (70%) 19 (44%) 24 (56%) Abstract 3725. Table 2. Association of treatment to Radiologist 2-rated typhlitis Enterocolitis Ileocecal region only Cecum No Yes P No Yes P No Yes P Treatment 0.86 0.98 0.29 DNA60 57 (77%) 17 (23%) 57 (77%) 17 (23%) 62 (84%) 12(16%) DNA90 36 (73%) 13 (27%) 37 (76%) 12 (24%) 36 (73%) 13 (27%) IDA 58 (73%) 21 (27%) 61 (77%) 18 (23%) 66 (84%) 13 (16%) Concomitant infection Yes 11 (26%) 32 (74%) 13 (30%) 30 (70%) 21 (49%) 22 (51%) Disclosures No relevant conflicts of interest to declare.

scholarly journals What is a clinically meaningful survival benefit in refractory metastatic colorectal cancer?

2019 ◽  
Vol 26 (2) ◽  
Author(s):  
Y. J. Ko ◽  
M. Abdelsalam ◽  
P. Kavan ◽  
H. Lim ◽  
P. A. Tang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Clinical Benefit ◽  
Policy Decision ◽  
Standard Of Care ◽  
Current Standard ◽  
Cancer Treatments ◽  
Medical Oncologists ◽  
Definition Of

Assessment of the clinical benefit of cancer treatments can be highly subjective, influenced by both perspective and context. Such assessments are required in regulatory and policy decision-making, but consistency between jurisdictions is often lacking. Clear and consistent standards for determining when a treatment offers a meaningful benefit, relative to the current standard of care, can help to address issues of equity and transparency in health technology assessment.    For metastatic colorectal cancer (mcrc), no standardized Canadian definition of clinically meaningful benefit has yet been proposed. Colorectal Cancer Canada therefore convened a group of medical oncologists expert in colorectal cancer to review the literature about clinical significance. The resulting consensus is intended to apply to any therapeutic agent being considered in the setting of chemotherapy-refractory mcrc.    It was agreed that overall survival is the appropriate measure of clinical efficacy in chemorefractory mcrc. As quantitative targets for efficacy, an improvement of 2 months or more in median overall survival or a hazard ratio for survival of 0.75 or lower (or both) are proposed as the threshold for clinically meaningful benefit. That threshold could be influenced by a treatment’s effect on quality of life. Treatment toxicity is also relevant to the assessment of clinical benefit in this setting, specifically when significant differences in treatment tolerability are evident.

Smoldering Multiple Myeloma: When to Observe and When to Treat?

2015 ◽  
pp. e484-e492 ◽  
Author(s):  
María-Victoria Mateos ◽  
Jesús-F San Miguel
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Correct Diagnosis ◽  
Standard Of Care ◽  
Current Standard ◽  
Smoldering Multiple Myeloma ◽  
Risk Of Progression ◽  
Bone Marrow Plasma ◽  
Risk Of Disease ◽  
Definition Of

Smoldering multiple myeloma (SMM) is an asymptomatic disorder characterized by the presence of at least 3 g/dL of serum M-protein and/or 10% to 60% bone marrow plasma cell infiltration with no myeloma-defining event. The risk of progression to active multiple myeloma (MM) is not uniform and several markers are useful for identifying patients at high risk of progression. The definition of the disease has recently been revisited and patients with asymptomatic MM at 80% to 90% of progression risk at 2 years are now considered to have MM. Although the current standard of care is not to treat, a randomized trial in patients with high-risk SMM that compared early treatment versus observation demonstrated that early intervention resulted in substantial benefits in terms of time to progression and overall survival (OS). These findings highlight the need to follow a correct diagnosis by an accurate risk stratification to plan an optimized follow-up according to the risk of disease progression.

scholarly journals Clinicians' Perspectives on Cure in Adult Acute Lymphoblastic Leukemia (ALL) Patients with Minimal Residual Disease (MRD) - Findings from a UK Delphi Panel

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5865-5865
Author(s):  
David Marks ◽  
Wendy Gidman ◽  
Heather M Wieffer ◽  
Lirong Zhang ◽  
Ze Cong ◽  
...  
Keyword(s):  
General Population ◽  
Standard Of Care ◽  
Delphi Panel ◽  
Current Standard ◽  
Employment Equity ◽  
Term Survival ◽  
Equity Ownership ◽  
Definition Of ◽  
Age And Sex

Abstract Introduction The presence of MRD in patients with Philadelphia chromosome-negative (Ph-) B-cell precursor (BCP) ALL in first complete remission (CR1) is an important negative prognostic factor. Evidence suggests that long term survival can be achieved among patients with MRD. However, what constitutes 'cure' is unclear; in addition, the definition of cure could be disease and stage specific. This study aimed to better understand the concept of cure in this patient population through a Delphi consensus panel approach, considering the definition of cure, the place of hematopoietic stem cell transplant (HSCT) in the treatment pathway, and long-term mortality risk and health-related quality of life (HRQL) in those patients who achieve cure. Methods Following ethical approval a two phase Delphi panel was conducted with five hematologists / hemato-oncologists from the UK with expertise in treating adults with ALL. Participants initially completed a questionnaire, which gathered data on participants' background and experience in ALL, as well as information on ALL treatments and outcomes using semi-structured and open-ended questions. Responses to the questionnaire were then presented and discussed by all participants in a web-based meeting. Participant "poll" questions were used to establish where consensus (defined here as 80% agreement among participants) was achieved on specific statements. Results Participants had a median 16 years' experience in treating adults with ALL, and had treated a median of 12 patients with Ph- BCP-ALL in the previous 12 months. For patients with Ph− BCP-ALL who have achieved CR1 and are MRD+, participants agreed that some patients can achieve cure with current standard of care treatment. Cure was agreed to be best defined using the measure of relapse-free survival (RFS) as opposed to persistent MRD- status and overall survival. Participants reached consensus that they would begin to consider cure at 3 years' RFS in this patient population, and that cure is considered highly probable if a patient is still relapse-free at 5 years. The proportion of patients who achieve cure was agreed to be up to 30% with current standard of care treatments and HSCT, but the likelihood of cure was considered to be lower among patients who are not eligible for HSCT. Although considered part of the standard of care, participants agreed that HSCT cannot be conducted in all patients, and long-term survival has been shown to be possible with the current standard of care in a minority of patients who are MRD+ at CR1 who do not undergo HSCT. Participants agreed that, in the "cured" population, the mortality risk would be higher than in the general population. Specifically, participants reached a consensus that the mortality rate among patients who achieved cure, and who had received HSCT, was 3-4 times higher compared with the age- and sex-matched general population in UK due to the long term effects of HCST and chemotherapy. Furthermore, the after effects of chemotherapy and HSCT, were described to have an impact on the HRQL of patients who achieve cure. Consensus was reached that, on average, the HRQL of these "cured" patients would be higher than the average HRQL of patients who have just achieved MRD- status after further treatment and closer to the age- and sex-matched general population. Conclusions This study provides evidence via clinical consensus on the concept of cure in patient with BCP-ALL with MRD at CR1 in UK and confirms that cure could be achieved in this population. The implications of this research are that therapies that effectively eradicate MRD, and induce long term RFS, may potentially increase the chance of cure. Disclosures Marks: Novartis: Consultancy; Amgen: Consultancy; Pfizer: Consultancy. Cong:Amgen: Employment, Equity Ownership. Shah:Amgen, Inc.: Employment, Equity Ownership.

scholarly journals Treatment of Smoldering Multiple Myeloma: Ready for Prime Time?

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1223
Author(s):  
E. Bridget Kim ◽  
Andrew J. Yee ◽  
Noopur Raje
Keyword(s):  
Multiple Myeloma ◽  
Early Intervention ◽  
Standard Of Care ◽  
Prime Time ◽  
Current Standard ◽  
Smoldering Multiple Myeloma ◽  
Preventative Strategy ◽  
History Of ◽  
Definition Of ◽  
Delay Progression

The current standard of care for smoldering multiple myeloma (SMM) is observation until there is end-organ involvement. With newer and more effective treatments available, a question that is increasingly asked is whether early intervention in patients with SMM will alter the natural history of their disease. Herein, we review the evolving definition of SMM and risk stratification models. We discuss evidence supporting early intervention for SMM—both as a preventative strategy to delay progression and as an intensive treatment strategy with a goal of potential cure. We highlight ongoing trials and focus on better defining who may require early intervention.

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.

scholarly journals Updated Insights on EGFR Signaling Pathways in Glioma

2021 ◽  
Vol 22 (2) ◽  
pp. 587
Author(s):  
Alexandru Oprita ◽  
Stefania-Carina Baloi ◽  
Georgiana-Adeline Staicu ◽  
Oana Alexandru ◽  
Daniela Elise Tache ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
Standard Of Care ◽  
Egfr Signaling ◽  
Current Standard ◽  
Egfr Amplification ◽  
Epidermal Growth ◽  
New Diagnosis ◽  
Clear Clinical Benefit

Nowadays, due to recent advances in molecular biology, the pathogenesis of glioblastoma is better understood. For the newly diagnosed, the current standard of care is represented by resection followed by radiotherapy and temozolomide administration, but because median overall survival remains poor, new diagnosis and treatment strategies are needed. Due to the quick progression, even with aggressive multimodal treatment, glioblastoma remains almost incurable. It is known that epidermal growth factor receptor (EGFR) amplification is a characteristic of the classical subtype of glioma. However, targeted therapies against this type of receptor have not yet shown a clear clinical benefit. Many factors contribute to resistance, such as ineffective blood–brain barrier penetration, heterogeneity, mutations, as well as compensatory signaling pathways. A better understanding of the EGFR signaling network, and its interrelations with other pathways, are essential to clarify the mechanisms of resistance and create better therapeutic agents.

A comparison between 25-gauge and 22-gauge Franseen needles for endoscopic ultrasound-guided sampling of pancreatic and peripancreatic masses: a randomized non-inferiority study

Endoscopy ◽  
2021 ◽  
Author(s):  
Dongwook Oh ◽  
Joonseog Kong ◽  
Sung Woo Ko ◽  
Seung-Mo Hong ◽  
Hoonsub So ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Endoscopic Ultrasound ◽  
Care Center ◽  
Tertiary Care ◽  
Standard Of Care ◽  
Fine Needle Biopsy ◽  
Needle Aspiration ◽  
Adverse Event Rate ◽  
Current Standard ◽  
Fine Needle

Abstract Background Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) and fine-needle biopsy (FNB) are the current standard of care for sampling pancreatic and peripancreatic masses. Recently, a 22G EUS-FNB needle with Franseen geometry was developed, and this device was also introduced in a 25G platform. We compared the performance of the 25G and 22G Franseen needles for EUS-guided sampling of pancreatic and peripancreatic solid masses. Methods We conducted a parallel-group randomized non-inferiority trial at a tertiary-care center from November 2018 to May 2019. The primary outcome was the quality of the histologic core assessed using the Gerke score. The optimal histologic core is indicated by a Gerke score of 4 or 5, which enables optimal histologic interpretation. The overall diagnostic accuracy and adverse event rate were also evaluated. Results 140 patients were enrolled and randomized (1:1) to the 25G and 22G groups. Tissue acquisition by EUS-FNB was successful in all patients. The optimal histologic core procurement rate was 87.1 % (61/70) for the 25G needle vs. 97.1 % (68/70) for the 22G; difference −10 % (95 % confidence interval −17.35 % to −2.65 %). High quality specimens were more frequently obtained in the 22G group than in the 25G group (70.0 % [49/70] vs. 28.6 % [20 /70], respectively; P < 0.001). The overall diagnostic accuracy did not differ between the groups (97.4 % for 25G vs. 100 % for 22G). Conclusions The 25G Franseen needle was inferior to the 22G needle in histologic core procurement. Therefore, for cases in which tissue architecture is pivotal for diagnosis, a 22G needle, which procures relatively higher quality specimens than the 25G needle, should be used.

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