CLO19-026: Determining the Treatment Decision of Tumors With Mixed Response

2019 ◽  
Vol 17 (3.5) ◽  
pp. CLO19-026
Author(s):  
Candice Baldeo ◽  
Tasneem Kaleem ◽  
Ricardo Paz-Fumagalli ◽  
John Copland ◽  
Michael Menefee

Introduction: Individuals receiving systemic anticancer therapies for advanced solid tumors routinely undergo imaging studies to assess the efficacy of the treatment. Mixed response (MR) to cancer therapy is a common but poorly described phenomenon. There is a paucity of data regarding both the incidence and possible mechanisms of this clinical quandary. Potential etiologies include tumor heterogeneity, differences in tumor microenvironment, and discrepancies in drug delivery to different tumor deposits. It is also possible that MR simply reflects differences in the rate of resistance emerging. MR represents a therapeutic dilemma for the clinician. Methods: Mixed tumor response was defined as: One tumor decreasing in size; one tumor increasing in size (classified as RECIST response/progressions), One tumor stable; another tumor progressing, One tumor stable; another tumor responding, New tumor; another tumor responding or remaining stable. Between 2015 and 2017, 120 restaging CT scans were reviewed of patients who had received at least 1 line of therapy for advanced cancer diagnosis which showed MR; hematologic malignancies were excluded. Charts were reviewed to determine the clinical decision that was made at the time of the MR. Results: A total of 120 scans with MR were reviewed from various solid tumor diagnoses. 38 scans were excluded due to loss of follow-up or death. Of the remaining 82 scans, therapy was switched in 30, the same therapy was continued in 50, and an additional agent was added to the current treatment in 2 cases (Table). Of the patients in which treatment was switched, 20% (6/30) showed response to treatment on the following scan. Of the cases that were kept on current treatment, none showed response on the following restaging scan which was done 6–8 weeks later. There were 4 (10%) deaths prior to the next scan in the group that had treatment switched and similarly 5 deaths (10%) prior to the next scan in the group in which treatment remained the same. Conclusion: MR is associated with a poor prognosis, irrespective of treatment decisions. These data are retrospective and our sample size is small, so definitive conclusions cannot be drawn. However, changing therapy when a MR is observed may be of benefit to some patients. A prospective evaluation to more accurately describe and understand the MR phenomenon is warranted.

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Sameera Shuaibi ◽  
Abdelrahman AlAshqar ◽  
Munirah Alabdulhadi ◽  
Wasl Al-Adsani

Abstract Introduction Renal echinococcosis is of rare occurrence, and although often asymptomatic, it can present with various mild to drastic presentations, of which hydatiduria is pathognomonic. Diagnosis can be preliminarily established by imaging, and treatment is primarily surgical. We present a patient with renal echinococcosis treated successfully with exclusive antiparasitic pharmacotherapy after refusing surgery despite extensive renal involvement. We hope through this report to help establish future solid guidelines regarding this uncommon therapeutic approach. Case presentation This is a case of a 49-year-old Syrian shepherd presenting with flank pain and passage of grape-skin-like structures in urine. A diagnosis of renal echinococcosis with hydatiduria and significant parenchymal destruction was established based on exposure history, positive serology, imaging findings, and renal scintigraphy. After proper counseling, the patient refused nephrectomy and was therefore started on dual pharmacotherapy (albendazole and praziquantel) and is having an uneventful follow-up and a satisfactory response to treatment. Conclusion This case embodies the daily challenges physicians navigate as they uphold the ethical principles of their practice and support their patients’ autonomy while delivering the best standards of care and consulting the scientific evidence. Although surgery is the cornerstone of renal echinococcosis treatment, treating physicians should be prepared to tackle situations where surgery cannot be done and offer the best next available option for patients who refuse surgery. As data on exclusive pharmacotherapy are limited, future research should thoroughly investigate the efficacy of this uncommon approach and outline reliable recommendations, facilitating future clinical decision-making in this avenue.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11012-11012
Author(s):  
Markus Wallwiener ◽  
Andreas D. Hartkopf ◽  
Sabine Riethdorf ◽  
Martin Sprick ◽  
Christoph Wolfram Domschke ◽  
...  

11012 Background: To prospectively assess the prognostic value of CTC counts at baseline and after one cycle of therapy and their kinetics for response, progression-free (PFS), and overall survival (OS) in MBC. Methods: MBC patients underwent CTC enumeration (CellSearch, Veridex) at baseline (CTCBL), after one cycle of a new line of therapy (CTC1C), and at progression (CTCPD). CTC status was classified as negative (neg (−)) or positive (pos (+)) for <5 and ≥5 CTC/7.5 ml peripheral blood, respectively. CTC kinetics (CTCKIN) from CTCBL to CTC1C were classified as favorable if CTCs remained neg (neg>neg) or became neg (pos>neg), or as unfavorable (neg>pos or pos>pos). Tumor response was assessed every 2–3 months using RECIST criteria. CTC status and kinetics were associated with outcome using log-rank and Fisher’s exact tests. Results: Of 326 patients enrolled (median age (range) at first diagnosis: 50 (23–81) years), 115/326 (35%) were CTCBL+, 51/162 (31%) were CTC1C+, and 39/108 (36%) were CTCPD+. Median follow-up was 15.9 months (mos). Median PFS and OS were significantly reduced in CTCBL+ compared to CTCBL− patients (PFS, 4.3 vs. 7.1 mos, p = .019; OS, 15.0 mos vs. not reached (nr), p <.001) and for CTC1C+ compared to CTC1C− patients (p <.001 for PFS and OS). CTCKIN were predictive of progressive disease as best response (neg>neg, 33%; pos>neg, 38%; pos>pos, 60%; neg>pos, 75%; p = .040). PFS and OS for patients with unfavorable CTCKIN were significantly shorter than for favorable CTCKIN (PFS, 3.7 vs. 6.8 mos, p <.001; OS, 7.8 mos vs. nr, p <.001). Conclusions: CTC at baseline, CTC after one cycle and CTC kinetics are highly predictive of outcome in MBC. Serial CTC enumeration could serve as a useful adjunct to standard diagnostic tests in tailoring therapy. Further details of CTCPD will be presented at the meeting. Clinical trial information: S-295/2009.


2021 ◽  
Author(s):  
P.K.A. Kearns ◽  
S.J. Martin ◽  
J. Chang ◽  
R. Meijboom ◽  
E.N. York ◽  
...  

ABSTRACTMultiple Sclerosis (MS) is an immune-mediated, neuroinflammatory disease of the central nervous system and in industrialised countries the most common cause of progressive neurological disability in working age persons. However, there is significant between-subject heterogeneity in disease activity and response to treatment. Currently, the ability to predict at diagnosis who will have a benign, intermediate, or aggressive disease course is very limited. There is therefore a need for integrated predictive tools to inform individualised treatment decision making. FutureMS is a nationally-representative, prospective observation cohort study comprising 440 participants with a new diagnosis of relapsing remitting MS living in Scotland between May 2016 and March 2019. Established with the aim of addressing this need for individualised predictive tools, the cohort is designed to combine detailed clinical phenotyping with imaging, genetic and biomarker metrics of disease activity and progression. Recruitment, baseline assessment and follow up at year one is complete and longer-term follow up is planned, beginning at five years after first visit. The study aims to address the biology and determinants of disease heterogeneity in MS. Here we describe the cohort design and present a profile of the participants at baseline and one year of follow up.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 7500-7500 ◽  
Author(s):  
Curtis Andrew Lachowiez ◽  
Gautam Borthakur ◽  
Sanam Loghavi ◽  
Zhihong Zeng ◽  
Tapan M. Kadia ◽  
...  

7500 Background: Mutations in the isocitrate dehydrogenase-1 gene ( IDH1) result in myeloid differentiation arrest and accumulation of the oncometabolite 2-hydroxyglutarate (2-HG), promoting leukemogenesis. We report a primary safety and efficacy analysis of the IDH1 inhibitor ivosidenib (IVO; 500 mg PO daily D15-continous) combined with venetoclax (VEN; D1-14 per 28-day cycle), with and without azacitidine (AZA; 75mg/m2 D1-7). Methods: Eligible patients age ≥18 with IDH1 mutated myeloid malignancies (high-risk MDS and AML) enrolled into one of three successive cohorts (Cohort 1: IVO+VEN 400 mg, Cohort 2: IVO+VEN 800 mg, Cohort 3: IVO+VEN 400 mg+AZA). Primary endpoints include safety and tolerability and overall response rate (ORR) by revised IWG criteria. Key secondary endpoints include survival endpoints and PK correlates. Results: 19 patients (median age 68) enrolled, 17 with AML: 9 relapsed/refractory AML (R/R; median 1 prior line of therapy), 5 treatment naïve AML, and 3 HMA-failure MDS with secondary AML. Two patients had high-risk MDS. ELN risk was favorable, intermediate, and adverse risk in 37%, 15%, and 47%. Co-mutations included NPM1 (37%), chromatin-spliceosome (32%), methylation (16%), and RAS pathway (21%). Adverse events of special interest included IDH differentiation syndrome (n=4, grade > 3 in 1) and tumor lysis syndrome (TLS; n=2), including one grade 3 TLS event in a NPM1+ patient (successfully managed without hemodialysis). In evaluable patients (n=18), composite complete remission (CRc: CR+CRi+CRh) rates were 78% overall (treatment naive: 100%, R/R: 75%), and 67%, 100%, and 67% by cohort (median time to best response: 2 months). 7 (50%) patients achieving CRc were also MRD negative by flow cytometry. 1 patient had HI without CR/CRi and 1 had a MLFS. 9 (50%) patients remain on study, 3 (17%) proceeded to SCT in CR, 2 were non-responders, and 5 (22%) experienced progressive disease following CRc occurring after a median of 3 months. After a median follow up of 3.5 months, median OS was not reached in treatment naïve patients, and 9.7 months in R/R patients. Conclusions: IVO+VEN +AZA therapy is well tolerated and highly effective for patients with IDH1 mutated AML. Follow up and accrual is ongoing to better define duration and biomarkers of response. Clinical trial information: NCT03471260 . [Table: see text]


Hematology ◽  
2012 ◽  
Vol 2012 (1) ◽  
pp. 604-609 ◽  
Author(s):  
James N. George ◽  
Zayd L. Al-Nouri

Abstract Evaluation and management of patients with suspected thrombotic thrombocytopenic purpura (TTP) continue to be a critical challenge for hematologists. The diagnostic criteria are not precise, often causing uncertainty about whether it is appropriate to initiate plasma exchange (PEX), the essential treatment for TTP. Initiation of PEX remains a clinical decision; severe ADAMTS13 (< 10% activity) deficiency alone is neither sufficiently sensitive nor specific for the diagnosis of TTP. However, patients who do have severe acquired ADAMTS13 deficiency define the characteristic clinical features of TTP, the response to treatment, and the long-term outcomes. Patients with severe acquired ADAMTS13 deficiency are predominantly young women and the relative frequency of blacks is increased. Patients may present with only microangiopathic hemolytic anemia and thrombocytopenia, neurologic and renal abnormalities are often not present, fever rarely occurs; the complete “pentad” of these clinical features almost never occurs in current practice. Response to PEX is typically rapid but may not be sustained when PEX is stopped. Use of corticosteroids and rituximab has decreased the number of PEX treatments required to achieve a remission and has resulted in fewer PEX-related major complications. Relapse (in approximately 40% of patients) may be the most apparent risk after recovery, but long-term health outcomes are also very important. Minor cognitive abnormalities are common, the frequency of depression is increased, and the frequency of hypertension is increased. Careful long-term follow-up of TTP patients is essential.


Author(s):  
Kapil Gargh ◽  
Eslam Al-Abadi ◽  
Samantha Low ◽  
Kathryn Harrison ◽  
William Coles ◽  
...  

AbstractThe Paediatric Rheumatology International Trials Organisation (PRINTO) criteria for clinically inactive disease (CID) and their proposal for glucocorticoid tapering do not consider MRI findings, despite the growing use of MRI and development of reliable MRI scoring tools. We aim to evaluate how CID correlates with MRI scores and physician decision making. We retrospectively used the Juvenile Dermatomyositis Imaging Score (JIS) to score MRIs of all children with JDM over a 10-year period. Demographic, diagnosis, treatment and core set measures data were collected. Correlation between CID and JIS was assessed as well as correlation with the physician treatment decision. There were 25 patients with 59 follow-up episodes to analyse correlation between physician treatment decision and JIS; and 50 episodes for the CID category and JIS correlation. JIS was not significantly associated with the CID category but did correlate with the physician decision. No significant association was found between clinical decision and CID category. The JIS area under the ROC curve (AUC) was 0.80 (95% CI 0.62–0.99) with a score ≥ 8 to predict an escalation. JIS sensitivity and specificity were both 78% with accuracy of 78%, compared to only 67%, 46% and 49%, respectively, for the CID criteria. Clinical criteria alone are not sufficient to assess disease activity status. Clinical decision trends correlated to MRI findings but not PRINTO CID criteria. Multi centre prospective studies are needed to replicate our findings and establish how to best use MRI as a biomarker of disease activity.


1968 ◽  
Vol 29 (2) ◽  
pp. 364-381 ◽  
Author(s):  
Alex D. Pokorny ◽  
Byron A. Miller ◽  
Sidney E. Cleveland

Med Phoenix ◽  
2017 ◽  
Vol 2 (1) ◽  
pp. 34-37
Author(s):  
Akhilesh Kumar Jha ◽  
Bikranta Rimal ◽  
Tarannum Khatun

Background: Ultrasonography is the reliable and safe way for the evaluation of pregnancy. Heart rate can be detected more confidently from the Ultrasonography. Heart rate is an important parameter for the evaluation of early pregnancy. The purpose of this study was to evaluate the normal heart rate in embryos/fetuses between 6 and 8 weeks of gestation.Method: In our region people are poor and most of them do not know the benefit of regular follow up examination during pregnancy. So most of pregnant women come to our centre at late stage of pregnancy. The number of pregnancy cases is good in our centre but the number of early pregnancy cases coming to regular follow up examination is low. Thus the study was conducted in 51 normal singleton pregnancies undergoing routine ultrasound examination during the first trimester of pregnancy. The duration of study was 6 weeks.Result: Out of 51 singleton pregnancies, 20 cases (39.2%) heart rate were between 131-150 beat per minute and 25 cases (49.0 %) heart rate were between 151-170 beat per minute. However 4 cases (7.8%) were between 110-120 beat per minute and 2 cases (3.9%) were more than 171 beat per minute. There were zero cases above the 180 beat per minute.Conclusion: The result of this study will help to evaluate abnormal and normal fetal heart rate so that early clinical decision whether to continue the pregnancy or terminate it can be taken, as Ultrasonography is only the method used in screening fetal well being in most of the region of our country.Med Phoenix Vol.2(1) July 2017, 34-37


2017 ◽  
Vol 63 (3) ◽  
pp. 461-465
Author(s):  
Lev Bershteyn ◽  
Dmitriy Vasilev ◽  
Tatyana Poroshina ◽  
Igor Berlev

Increased frequency of endometrial cancer (EC) since the beginning of this century exceeds that of breast cancer and to a large extent can be attributed to dynamics of parameters, which characterize hormonal and metabolic status of ill women and molecular genetic landscape of transforming endometrium. During the past few years there are suggested several options for a personalized assessment of the risk of EC. The aim of this article is to propose and justify own version of this score with the idea of its further not only retrospective but also prospective testing both in relation to the risk of developing endometrial cancer as well as an additional marker helping to predict tumor response to treatment.


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