Correlation between expression of MCM6, a new proliferative marker, and treatment outcome in patients with Hodgkin's disease

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19547-e19547
Author(s):  
K. Khodadad ◽  
S. Karimi ◽  
Z. Esfahani Monfared

e19547 Background: MCM6 is a proliferative marker, which in contrary to Ki67, is involved in all cell cycle phases, including early G1. We evaluated MCM6 expression in Hodgkin's disease (HD) patients in order to find any correlation between MCM6 expression and treatment outcome. Methods: Formalin-fixed paraffin-embedded lymph node specimens of 55 patients with HD treated with ABVD regimen (± radiotherapy) were assessed for MCM6 expression by IHC. The percentage of nuclear positivity in RS and mononuclear Hodgkin cells was evaluated in each case. Clinical data, response to treatment and relapse rates were obtained from patients’ medical records. These data were analyzed by SPSS software. Results: Mean MCM6 expression was 80.7% (ranging 35%-99%) with no significant difference between histology subtypes. In univariate analysis, MCM6 expression was not statistically significant for B-symptoms (P=0.27), sex (P=0.91), stage (P=0.18) and response to treatment (P=0.53), but was significant for age (P=0.008) (≤23 vs >23 yrs old). The MCM6 mean expression between relapsed and non-relapsed groups was marginally significant (21% vs 29.4%, P=0.057). In multivariate analysis, we evaluated MCM6 expression, B-symptoms, stage, response rate and age for relapse. None of risk factors were statistically significant predictor for relapse, including MCM6 expression (P=0.238), however, were significant regarding to response (P<0.001) and stage (P=0.048). We divided patients in 4 quartiles based on their MCM6 expression (Q1<74.25%, N=13, Q2=74.26–85.5%, N=14, Q3=85.6–91.75%, N=13, Q4>91.75%, N=12). Relapse and PFS were not significantly different between these quartiles (P=0.27 and P=0.83, respectively). Conclusions: Our study on a limited number of patients revealed MCM6 is not a strong predictor for treatment outcome in patients with HD. Our findings can be possibly explained by early G1 arrest of tumor cells and the role of cytokine production in pathogenesis of HD. We believe determining the accurate predictive role of proliferative markers needs to be focused on the markers which are exclusively involved in S phase. No significant financial relationships to disclose.

1993 ◽  
Vol 79 (2) ◽  
pp. 133-136 ◽  
Author(s):  
Guseppe Pellegris ◽  
Claudia Lombardo ◽  
Annelisa Cantoni ◽  
Liliana Devizzi ◽  
Monica Balzarotti

Background A number of reports have studied associations between Hodgkin's disease and HLA. Some of them established correlation between several antigens and Hodgkin's disease, and others found no correlations. Methods The HLA DP locus was determined by the polymerase chain reaction method in 31 Hodgkin's disease patients and 58 healthy controls. Results No significant difference between patients and controls was noted. Conclusions Further investigations are needed to confirm the hypothesis of a possible role of the HLA complex as one of the factors involved in Hodgkin's disease.


2003 ◽  
Vol 21 (10) ◽  
pp. 2026-2033 ◽  
Author(s):  
Ron S. Smith ◽  
Qing Chen ◽  
Melissa M. Hudson ◽  
Michael P. Link ◽  
Larry Kun ◽  
...  

Purpose: Evaluation of pretreatment factors to identify children at high risk for relapse after combined-modality therapy for Hodgkin’s disease. Patients and Methods: From 1990 to 2000, 328 pediatric patients with clinical stage I to IV Hodgkin’s disease were treated with chemotherapy and low-dose involved-field radiotherapy on prospective, collaborative, risk-adapted protocols at three institutions. Pretreatment factors were analyzed by univariate and multivariate analysis for prognostic significance for 5-year disease-free survival (DFS) and overall survival (OS). Results: With a median follow-up of 59 months (range, 8 to 125 months), the 5-year DFS and OS for all patients were 83% and 93%, respectively. Several factors were associated with inferior DFS and OS by univariate analysis. By multivariate analysis, male sex; stage IIB, IIIB, or IV disease; bulky mediastinal disease; WBC more than 13.5 × 103/mm3; and hemoglobin less than 11.0 g/dL were significant for inferior DFS. A prognostic index was developed incorporating the five significant factors from the multivariate analysis, assigning each a score of 1. The 5-year DFS and OS for children with a prognostic score of 0 to 1 were 94% and 99%; score 2, 85% and 96%; score 3, 71% and 92%; and score 4 or 5, 49% and 72%, respectively. There was a significant difference in DFS among each of these groups, with significantly worse OS in those with a score of 4 to 5. Conclusion: A prognostic index that was based on five pretreatment factors correlated with inferior DFS by multivariate analysis stratified patients by outcome; this may be useful in assigning children with Hodgkin’s disease to risk-adapted therapy.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9033-9033
Author(s):  
M. Weyl Ben Arush ◽  
A. Ben Barak ◽  
P. Shenzer ◽  
S. Maurice ◽  
E. Livne

9033 Background: The aim of this pilot study was to determine VEGF serum levels (S-VEGF) at diagnosis and at restaging in children diagnosed with Hodgkin’s disease, and to investigate whether this parameter provides prognostic information for remission after 2 courses of chemotherapy Methods: S-VEGF levels of 9 consecutive pediatric patients (pts) with Hodgkin’s disease were assayed at diagnosis and at restaging. Levels of VEGF were determined using a commercially available ELISA anti-human VEGF immunoassay kit. PET-CT fusion was performed for each child at diagnosis and after 2 courses of chemotherapy in order to assess response to treatment. Results: 8 children went into complete remission or very good partial response after 2 courses of chemotherapy according to the protocol, one child developed tumor progression and respond to second line chemotherapy. At diagnosis average S-VEGF level was 655.7pg/ml (range, 1078.7–29.22 pg/ml) and at restaging decreased to 237.6 pg/ml (range, 0–453 pg/ml). (p=0.0039). One child with Hodgkin’s disease who had a higher level at first restaging and developed progressive disease responded to reinduction therapy and had a significantly lower level at the second restaging. The comparison between the levels of S-VEGF at diagnosis and at restaging showed a significant difference for the pts who responded to treatment with decreased S-VEGF and the pt who developed tumor progression with increased S-VEGF. Conclusions: Changes in S-VEGF levels correlated with response to treatment for most of the children diagnosed with Hodgkin’s disease. This provides a rationale for exploring clinical interest in S-VEGF measurements of a larger group of children with Hodgkin, and using the test for clinical trials of antiangiogenic therapies. No significant financial relationships to disclose.


Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3952
Author(s):  
Andrea Gallamini ◽  
Michał Kurlapski ◽  
Jan Maciej Zaucha

In the present review, the authors report the published evidence on the use of functional imaging with FDG-PET/CT in assessing the final response to treatment in Hodgkin lymphoma. Despite a very high overall Negative Predictive Value of post-chemotherapy PET on treatment outcome ranging from 94% to 86%, according to different treatment intensity, the Positive Predicting Value proved much lower (40–25%). In the present review the Authors discuss the role of PET to guide consolidation RT over a RM after different chemotherapy regimens, both in early and in advanced-stage disease. A particular emphasis is dedicated to the peculiar issue of the qualitative versus semi-quantitative methods for End-of Therapy PET scan interpretation. A short hint will be given on the role of FDG-PET to assess the treatment outcome after immune checkpoint inhibitors.


Chemotherapy ◽  
2021 ◽  
pp. 1-8
Author(s):  
Angelo Onorato ◽  
Andrea Napolitano ◽  
Silvia Spoto ◽  
Lorena Incorvaia ◽  
Antonio Russo ◽  
...  

<b><i>Background:</i></b> Fatigue is a common distressing symptom for patients living with chronic or acute diseases, including liver disorders and cancer (<i>Cancer-Related Fatigue</i>, CRF). Its etiology is multifactorial, and some hypotheses regarding the pathogenesis are summarized, with possible shared mechanisms both in cancer and in chronic liver diseases. A deal of work has investigated the role of a multifunctional molecule in improving symptoms and outcomes in different liver dysfunctions and associated symptoms, including chronic fatigue: S-adenosylmethionine (SAM; AdoMet). The aim of this work is actually to consider its role also in oncologic settings. <b><i>Patients and Methods:</i></b> Between January 2006 and December 2009, at the University Campus Bio-Medico of Rome, 145 patients affected by colorectal cancer in adjuvant (<i>n</i> = 91) or metastatic (<i>n</i> = 54; <i>n</i> = 40 with liver metastases) setting and treated with oxaliplatin-based regimen (FOLFOX for adjuvant and bevacizumab + XELOX for metastatic ones), 76 of which with the supplementation of S-adenosylmethionine (AdoMet; 400 mg b.i.d.) (57% of adjuvant patients and 44% of metastatic ones) and 69 without AdoMet supplementation, were evaluated for fatigue prevalence using the Functional Assessment of Chronic Illnesses Therapy-Fatigue (FACIT-F) questionnaire, at 3 and 6 months after the beginning of oncologic treatment. Notably, the number of patients with liver metastases was well balanced between the group of patients treated with AdoMet and those who were not. <b><i>Results:</i></b> Among patients receiving oxaliplatin-based chemotherapy, both in adjuvant and in metastatic settings, after just 3 months from the beginning of chemotherapy, mean scores from questionnaire domains like FACIT-F subscale (7.9 vs. 3.1, <i>p</i> = 0.006), FACIT physical (6.25 vs. 3.32, <i>p</i> = 0.020), FACIT emotional (4.65 vs. 2.19, <i>p</i> = 0.045), and FACIT-F total score (16.5 vs. 8.27, <i>p</i> = 0.021) were higher in those receiving supplementation of AdoMet, resulting in reduced fatigue; a significant difference was maintained even after 6 months of treatment. <b><i>Discussion and Conclusions:</i></b> Mechanisms and strategies for managing CRF are not fully understood. This work aimed at investigating the possible role of S-adenosylmethionine supplementation in improving fatigue scores in a specific setting of cancer patients, using a FACIT-F questionnaire, a well-validated quality of life instrument widely used for the assessment of CRF in clinical trials.


1986 ◽  
Vol 4 (4) ◽  
pp. 472-479 ◽  
Author(s):  
M J Crnkovich ◽  
R T Hoppe ◽  
S A Rosenberg

Between 1968 and 1982, 126 patients with pathologic stage (PS) IIB Hodgkin's disease were treated at Stanford University with either irradiation alone or irradiation combined with chemotherapy. Actuarial survival and freedom from relapse rates at 10 years for the overall group were 81% and 74% respectively, with no statistically significant difference between the treatment approaches. The impact of the severity and number of constitutional (B) symptoms, as defined by the Ann Arbor Conference, was analyzed. Patients who presented with all three B symptoms had significantly poorer survival and freedom from relapse compared with those patients with only one or two B symptoms (for survival differences, P = .005 and .007; for freedom from relapse differences, P = .002 and .04). Male sex was the only other prognostic factor that correlated with a poor outcome. At 10 years, the survival rate was 66% for males v 84% for females (P = .01), and the freedom from relapse rate was 75% for males v 89% for females (P = .02). The presence of extralymphatic sites of involvement, age greater than 40, or involvement of greater than three lymphoid sites had no significant adverse effect on either freedom from relapse or survival. Patients with large mediastinal masses treated with irradiation alone had a 10-year freedom from relapse rate of 54% v 81% for those treated with combined-modality therapy (P = .15), but there was no significant difference in survival rates (85% for irradiation alone v 71% for combined modality therapy). Treatment recommendations for stage IIB Hodgkin's disease are discussed.


1983 ◽  
Vol 69 (5) ◽  
pp. 463-467
Author(s):  
Teodoro Chisesi ◽  
Orlando Ricciardi ◽  
Sandra Dal Fior ◽  
Francesco Cappellari ◽  
Franco Pozza ◽  
...  

Forty-nine patients with previously untreated advanced Hodgkin's disease were treated in our Institution between 1973 and 1981. Treatment modalities of these patients were reviewed, and they were divided into 3 groups according to the treatment employed: 13 patients received MOPP only, 22 patients received MOPP plus involved field radiotherapy, and 14 received alternating MOPP/ABVD chemotherapy. The response rates for the 3 groups were respectively 38.5%, 63.6% and 78.6%. A longer follow-up is needed to assess a significant difference in survival curves. The advantages of adjuvant radiotherapy and alternating non-cross-resistant drugs in advanced Hodgkin's disease are discussed.


1988 ◽  
Vol 6 (10) ◽  
pp. 1558-1561 ◽  
Author(s):  
R B Geller ◽  
G B Vogelsang ◽  
J R Wingard ◽  
A M Yeager ◽  
W H Burns ◽  
...  

Five patients with acute myelocytic leukemia (AML) after combined modality therapy for Hodgkin's disease (HD) were treated with cyclophosphamide and busulfan followed by bone marrow transplantation (BMT). Four patients received allogeneic transplants from histocompatibility locus antigen (HLA)-compatible siblings and the fifth patient received an autologous marrow treated with 4-hydroperoxycyclophosphamide. Two patients died of complications of acute graft-v-host disease (GVHD) despite prophylaxis with either low-dose cyclophosphamide or cyclosporine. The remaining three patients were alive and disease-free 382, 617, and 620 days after transplant. These initial results are encouraging and more patients with treatment-related AML need to be evaluated with both allogeneic and autologous BMT to fully elucidate the potentially curative role of this intensive therapy in an otherwise fatal hematologic malignancy.


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