scholarly journals Diagnostic Use of Post-therapy 131I-Meta-Iodobenzylguanidine Scintigraphy in Consolidation Therapy for Children with High-Risk Neuroblastoma

Diagnostics ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 663
Author(s):  
Hiroshi Wakabayashi ◽  
Daiki Kayano ◽  
Anri Inaki ◽  
Raita Araki ◽  
Rie Kuroda ◽  
...  
Keyword(s):  
High Risk ◽  
Residual Disease ◽  
Whole Body ◽  
Primary Therapy ◽  
Consolidation Therapy ◽  
Mibg Scintigraphy ◽  
Diagnostic Use ◽  
131I Mibg ◽  
Post Therapy ◽  
Abnormal Uptake

123I-meta-iodobenzylguanidine (123I-mIBG) scintigraphy is used for evaluating disease extent in children with neuroblastoma. 131I-mIBG therapy has been used for evaluation in children with high-risk neuroblastoma, and post-therapy 131I-mIBG scintigraphy may detect more lesions compared with diagnostic 123I-mIBG scintigraphy. However, no studies have yet revealed the detection rate of hidden mIBG-avid lesions on post-therapy 131I-mIBG whole-body scan (WBS) and SPECT images in neuroblastoma children without mIBG-avid lesions as demonstrated by diagnostic 123I-mIBG scintigraphy. We retrospectively examined the diagnostic utility of post-therapy 131I-mIBG scintigraphy in children who received 131I-mIBG as consolidation therapy. Nineteen children with complete response to primary therapy were examined. Post-therapy 131I-mIBG scintigraphy was performed four days after injection. The post-therapy 131I-mIBG scintigraphy, 4 children exhibited abnormal uptake on the WBS. Post-therapy 131I-mIBG SPECT/CT provided additional information in 2 cases. In total, 6 children exhibited abnormal uptake. The site of abnormal accumulation was on the recurrence site in one case, operation sites in five cases, and bone metastasis in one case. Post-therapy 131I-mIBG scintigraphy could detect residual disease that was not recognized using diagnostic 123I-mIBG scintigraphy in 32% of children with high-risk neuroblastoma and ganglioneuroblastoma. The diagnostic use of post-therapy 131I-mIBG scintigraphy can provide valuable information for detecting residual disease.

Quantitative Monitoring of NPM1 Mutation A Minimal Residual Disease Identifies Patients At High Risk for Relapse within the ELN Favorable Risk Group

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1404-1404
Author(s):  
Max Hubmann ◽  
Marion Subklewe ◽  
Thomas Köhnke ◽  
Stephanie Schneider ◽  
Annika Dufour ◽  
...  
Keyword(s):  
High Risk ◽  
Induction Therapy ◽  
Residual Disease ◽  
Risk Group ◽  
Disease Recurrence ◽  
Consolidation Therapy ◽  
Rt Pcr ◽  
Npm1 Mutation ◽  
Minimal Residual

Abstract Abstract 1404 Introduction: Molecular analyses of leukemia-specific markers has led to an improvement of the prognosis evaluation in patients (pts) with acute myeloid leukemia (AML). The European Leukemia Net (ELN) has published a classification which separates different subgroups by cytogenetic and molecular genetic analyses. Nevertheless, there are still pts suffering from disease recurrence within the ELN favorable risk group. To identify these pts at high risk for relapse the monitoring of minimal residual disease (MRD) of leukemia-specific markers could become an important diagnostic tool. In this study the potential of MRD monitoring by quantitative real-time PCR (RT-PCR) of NPM1 A mutation (NPM1 A) at different checkpoints within the ELN favorable risk group of pts with NPM1 A and without FLT3-ITD was investigated. Methods: Pts participating in the AMLCG99, AMLCG2004, and AMLCG2008 trial were prospectively or retrospectively screened for NPM1 mutation and FLT3-ITD by melting curve analyses. 334 pts were screened positive for NPM1 mutation and 262 pts showed a NPM1 A, 78.4 % of all NPM1 mutations. For MRD monitoring a relative RT-PCR was performed in 538 samples of 178 NPM1 A positive pts with a sensitivity of 10-6. MRD was monitored at diagnosis, in aplasia, after induction therapy, after consolidation therapy, and during the follow-up. MRD levels were normalized to the housekeeping gene ABL1 and expressed as a ratio to an internal control of known concentration. Results: In the analysis of the NPM1 A positive and FLT3-ITD negative pts (ELN favorable risk group) 82.5% (n=85) achieved complete remission (CR) after induction therapy. With a median follow-up of 26 (range 1–118) months, 36 (42.9%) pts relapsed within this subgroup. In aplasia, and after induction therapy, pts with a long-lasting remission showed significantly lower NPM1 A ratios in contrast to pts who relapsed during the follow-up. Via Receiver-Operating Curves (ROC) we analyzed the diagnostic power to identify pts at high risk for relapse and determined clinical useable cut-offs at the different checkpoints. ROC were significantly associated with disease recurrence at the checkpoints in aplasia and after induction therapy, but not after consolidation therapy. After induction therapy, a cut-off with a ratio of 0.01 was determined. This cut-off separates the patient cohort into two prognostic groups. NPM1 A MRD levels above the cut-offs result in an increased risk of relapse compared to pts with MRD level below this cut-off. This is reflected in a significantly lower 2-year relapse free survival (RFS) of 18% versus 72% (Figure 1). In 25 pts of this favorable risk group follow-up samples in CR were available for analysis of an upcoming relapse within 100 days of sampling. Only 2 of these pts developed relapse within of the next 100 days, but both pts showed increasing MRD levels prior to relapse. 18 relapse samples were available in this subgroup and interestingly, one patient (5.5%) was NPM1 A negative at relapse. When we further enrolled the FLT3-ITD positive pts into our analyses, not surprisingly we found a negative impact on the RFS of MRD positive and MRD negative pts. Conclusions: Our results confirm the observations of other studies that showed the prognostic impact of NPM1 MRD monitoring by RT-PCR. With the MRD monitoring we could identify pts at high risk for relapse within the ELN favorable risk group. Particularly high MRD levels after the induction therapy were strongly associated with a worse RFS. This and previously published data of others demonstrate that in addition to pre-therapeutic factors, the individual MRD course should be used as prognostic factor for the guidance of treatment and pts with high or increasing levels of MRD should undergo allogeneic stem cell transplantation, if eligible. Disclosures: No relevant conflicts of interest to declare.

A comparison of the effectiveness of 131I whole body scans and plasma Tg determinations in the diagnosis of metastatic differentiated carcinoma of the thyroid: a retrospective study

1983 ◽  
Vol 104 (3) ◽  
pp. 327-332 ◽  
Author(s):  
M. Hüfner ◽  
H. P. Stumpf ◽  
M. Grussendorf ◽  
H.J. Hermann ◽  
B. Kimmig
Keyword(s):  
Differentiated Thyroid Carcinoma ◽  
Whole Body ◽  
Suppressive Therapy ◽  
Primary Therapy ◽  
Whole Body Scan ◽  
Body Scan ◽  
Disease Free Interval ◽  
Disease Free ◽  
Post Therapy

Abstract. In 68 patients with proved metastases of differentiated thyroid carcinoma the comparative value of the 131I whole body scan and plasma Tg measurements in establishing the diagnosis of metastasis or recurrence was analyzed retrospectively. At the time of primary therapy most metastases were diagnosed by the post-therapy scan (78%). Eight of 9 scintigraphic negative metastases in the post-therapy scan were indicated by elevated Tg levels (> 10 ng/ml). Twenty-four of 28 recurrences after a disease free interval were negative in the 2 mCi 131I scan, 18 of these patients were Tg positive. Of the 4 recurrences with positive 131I uptake all were Tg positive; two of them only during endogenous TSH stimulation. It is conlcuded that the routine 2 mCi whole body scan is less efficient in follow-up than is generally assumed. The most important follow-up parameter for these patients is the plasma Tg which can be obtained under suppressive therapy if a sensitive assay is used. In patients with a negative post-therapy scan and a negative Tg (< 5 ng/ml) it seems justified to omit further 131I whole body control scans as long as Tg remains negative.

Cytogenetic Risk Groups and Minimal Residual Disease Are Strong Prognostic Factors for Post-Transplant Outcome in Patients with Acute Myeloid Leukaemia and Myelodysplastic Syndrome

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4482-4482
Author(s):  
Olga Blau ◽  
Katja Graul ◽  
Annette Sindram ◽  
Eckhard Thiel ◽  
Igor Wolfgang Blau
Keyword(s):  
High Risk ◽  
Residual Disease ◽  
Molecular Genetic ◽  
Intermediate Risk ◽  
Consolidation Therapy ◽  
Reduced Intensity Conditioning ◽  
Myeloablative Conditioning ◽  
Minimal Residual ◽  
Reduced Intensity ◽  
Acute Myeloid

Abstract Abstract 4482 Allogeneic stem cell transplantation (alloSCT) is a curative treatment option for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Relapse after alloSCT is still a major cause for the treatment failure. Molecular genetic (FLT3, NPM1 mutations) and cytogenetic risk-categories have an important impact on the prognosis of patients undergoing alloSCT. However, it has been shown that there is a closely relationship between the level of minimal residual disease (MRD) and relapse after alloSCT in leukemia patients. We analyzed 140 AML/MDS patients transplanted at our institution. We examined the contribution of cytogenetic aberrations and molecular genetic markers detected prior alloSCT to survival, relapse, and mortality after transplantation. Furthermore, we analyzed MRD status after consolidation therapy and in post-transplant period. We classified molecular genetic/cytogenetic status before alloSCT into 2 groups: low-risk: good and intermediate-risk karyotype, FLT3-wt, NPM1-mutated cases and high-risk: adverse-risk cytogenetic, FLT3-ITD mutated cases. A good risk karyotype was present in 8 patients; an intermediate risk in 56 patients, whereas 76 patients had a poor cytogenetic risk. 51 patients were treated with standard myeloablative conditioning regiments prior to alloSCT, 73 patients received reduced intensity conditioning and 16 non-myeloablative conditioning. 40 patients had a matched-related donor and 100 patients had a matched-unrelated donor. Overall survival (OS) in the group of patients with low cytogenetic risk was 839 days as compared with 613 days in high-risk group. The low risk cohort also showed a lower relapse (33% vs. 51%, p<0,03) and mortality rate (20% vs. 71%, p<0,003). We analyzed MRD status in all patients after consolidation therapy. MRD negative patients are characterized by favorable prognosis as compared with MRD positive patients, OS 87% vs. 53%, p<0,001. We conclude that risk-stratification combining molecular genetics and cytogenetics aberrations at the time of diagnosis with post-consolidation MRD status improve identification of high-risk category of patients. New treatment strategies are needed to overcome poor outcome of high risk AML patients, for instance, immunotherapy options like prophylactic DLI, shorter and modified immunosuppression, specific reduced intensity conditioning or new drugs like tyrosine kinase inhibitors. Disclosures: No relevant conflicts of interest to declare.

Differentiated thyroid cancer – 2009

2011 ◽  
Vol 152 (5) ◽  
pp. 163-170
Author(s):  
András Konrády
Keyword(s):  
Thyroid Cancer ◽  
High Risk ◽  
Genetic Alterations ◽  
New Drugs ◽  
Cytotoxic Agents ◽  
Whole Body ◽  
Iodine Uptake ◽  
Radioguided Surgery ◽  
Primary Therapy ◽  
Limited Surgery

Three years ago continental guidelines were published referring management and follow-up of low risk thyroid cancer patients. The aim of this paper is to summarize the changes and new directions in this field. High risk patients require another protocol. Neck ultrasound plays important role in differential diagnosis and in detecting recurrences. Some new ultrasound techniques are discussed, too. FDG-PET can help to solve the problem of patients having negative scan and increased thyroglobulin level. In recent years there was an expansion of our knowledge about the pathomechanism of thyroid cancer. It appears that genetic alterations frequently play a key role in carcinogenesis. There are molecular methods that allow the detection of these genetic events in thyroid fine needle aspirations samples providing important information for diagnosis, management and prognosis. Instead of diagnostic whole body scanning the posttherapeutic scan became preferable but in high risk cases the diagnostic whole body scintigrams serve useful data. Primary therapy of thyroid cancer is an adequate surgery: total thyreoidectomy and, if necessary, lymph node dissection or limited surgery in selected cases. Nowadays radioguided surgery can help to improve the results. Radioiodine therapy (e.g. rest ablation) proved to be a safe and effective method to complete surgery. It can prevent relapses and results in longer survival. Thyroid hormone withdrawal or recombinant human thyrotropin stimulation can increase thyrotropin level before radioiodine treatment. These two methods have similar success rate of rest ablation but irradiation burden of blood is lower in the case of exogenous stimulation which avoids hypothyroid state and preserves quality of life. Since tumor cells fail to maintain the ability to perform physiological functions they undergo dedifferentiation. Therefore, an important aim is to reactivate some function of differentiated cells, e.g. iodine uptake, production of thyroperoxydase and thyroglobulin. Opportunities for this therapeutic effort are also mentioned. Restoration of iodine uptake enables radioisotope treatment. Until now there has been little interest in the development of new drugs for the treatment of thyroid cancer. However, advances in our understanding of tumor cell biology will lead to a paradigm shift in the therapy that is likely to benefit patients who have high risk disease and who do not almost have any therapeutic option. There are new drugs in clinical trials that appear to be more effective than earlier cytotoxic agents. Probably modern chemotherapy of advanced thyroid cancer will have significant results in the near future. Orv. Hetil., 2011, 152, 163–170.

scholarly journals Evidence-Based Minireview: Does achieving MRD negativity after initial therapy improve prognosis for high-risk myeloma patients?

Hematology ◽  
2019 ◽  
Vol 2019 (1) ◽  
pp. 142-147 ◽  
Author(s):  
Surbhi Sidana ◽  
Elisabet Manasanch
Keyword(s):  
High Risk ◽  
Residual Disease ◽  
Staging System ◽  
Complete Response ◽  
Initial Therapy ◽  
Autologous Stem Cell Transplant ◽  
Whole Body ◽  
Cell Transplant ◽  
Positron Emission ◽  
International Staging System

You are evaluating a 47-year-old man with revised international staging system stage III myeloma who recently underwent an autologous stem cell transplant after receiving 6 cycles of carfilzomib, lenalidomide, and dexamethasone for newly diagnosed disease. Fluorescence in situ hybridization testing at initial presentation also revealed t(4;14). On day 100 evaluation after transplant, he has achieved a stringent complete response. Two-tube, 8-color advanced flow cytometry with a sensitivity of 10−5 shows no minimal residual disease. Whole-body positron emission tomography/computed tomography scan shows resolution of all fluorodeoxyglucose avid uptake seen at diagnosis. The patient asks you how these test results impact his prognosis and whether this overcomes his baseline high risk from t(4;14)?

scholarly journals Cisplatin +/− rucaparib after preoperative chemotherapy in patients with triple-negative or BRCA mutated breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Maitri Kalra ◽  
Yan Tong ◽  
David R. Jones ◽  
Tom Walsh ◽  
Michael A. Danso ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Neoadjuvant Therapy ◽  
Triple Negative ◽  
Residual Disease ◽  
Disease Free Survival ◽  
Parp Inhibition ◽  
High Risk Population ◽  
Risk Population ◽  
The Impact

AbstractPatients with triple-negative breast cancer (TNBC) who have residual disease after neoadjuvant therapy have a high risk of recurrence. We tested the impact of DNA-damaging chemotherapy alone or with PARP inhibition in this high-risk population. Patients with TNBC or deleterious BRCA mutation (TNBC/BRCAmut) who had >2 cm of invasive disease in the breast or persistent lymph node (LN) involvement after neoadjuvant therapy were assigned 1:1 to cisplatin alone or with rucaparib. Germline mutations were identified with BROCA analysis. The primary endpoint was 2-year disease-free survival (DFS) with 80% power to detect an HR 0.5. From Feb 2010 to May 2013, 128 patients were enrolled. Median tumor size at surgery was 1.9 cm (0–11.5 cm) with 1 (0–38) involved LN; median Residual Cancer Burden (RCB) score was 2.6. Six patients had known deleterious BRCA1 or BRCA2 mutations at study entry, but BROCA identified deleterious mutations in 22% of patients with available samples. Toxicity was similar in both arms. Despite frequent dose reductions (21% of patients) and delays (43.8% of patients), 73% of patients completed planned cisplatin. Rucaparib exposure was limited with median concentration 275 (82–4694) ng/mL post-infusion on day 3. The addition of rucaparib to cisplatin did not increase 2-year DFS (54.2% cisplatin vs. 64.1% cisplatin + rucaparib; P = 0.29). In the high-risk post preoperative TNBC/BRCAmut setting, the addition of low-dose rucaparib did not improve 2-year DFS or increase the toxicity of cisplatin. Genetic testing was underutilized in this high-risk population.

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