scholarly journals Risk-Adapted Dose-Dense Immunochemotherapy Determined by Interim FDG-PET in Advanced-Stage Diffuse Large B-Cell Lymphoma

2010 ◽  
Vol 28 (11) ◽  
pp. 1896-1903 ◽  
Author(s):  
Craig H. Moskowitz ◽  
Heiko Schöder ◽  
Julie Teruya-Feldstein ◽  
Camelia Sima ◽  
Alexia Iasonos ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Pet Scan ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Positive Biopsy ◽  
Fdg Pet Scan ◽  
Dose Dense ◽  
Pet Scans

Purpose In studies of diffuse large B-cell lymphoma, positron emission tomography with [18F]fluorodeoxyglucose (FDG-PET) performed after two to four cycles of chemotherapy has demonstrated prognostic significance. However, some patients treated with immunochemotherapy experience a favorable long-term outcome despite a positive interim FDG-PET scan. To clarify the significance of interim FDG-PET scans, we prospectively studied interim FDG-positive disease within a risk-adapted sequential immunochemotherapy program. Patients and Methods From March 2002 to November 2006, 98 patients at Memorial Sloan-Kettering Cancer Center received induction therapy with four cycles of accelerated R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by an interim FDG-PET scan. If the FDG-PET scan was negative, patients received three cycles of ICE (ifosfamide, carboplatin, and etoposide) consolidation therapy. If residual FDG-positive disease was seen, patients underwent biopsy; if the biopsy was negative, they also received three cycles of ICE. Patients with a positive biopsy received ICE followed by autologous stem-cell transplantation. Results At a median follow-up of 44 months, overall and progression-free survival were 90% and 79%, respectively. Ninety-seven patients underwent interim FDG-PET scans; 59 had a negative scan, 51 of whom are progression free. Thirty-eight patients with FDG-PET–positive disease underwent repeat biopsy; 33 were negative, and 26 remain progression free after ICE consolidation therapy. Progression-free survival of interim FDG-PET–positive/biopsy-negative patients was identical to that in patients with a negative interim FDG-PET scan (P = .27). Conclusion Interim or post-treatment FDG-PET evaluation did not predict outcome with this dose-dense, sequential immunochemotherapy program. Outside of a clinical trial, we recommend biopsy confirmation of an abnormal interim FDG-PET scan before changing therapy.

Sequential Dose-Dense RCHOP Followed by ICE Consolidation (MSKCC protocol 01–142) without Radiotherapy for Patients with Primary Mediastinal Large B Cell Lymphoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 420-420 ◽  
Author(s):  
Craig Moskowitz ◽  
Paul A Hamlin ◽  
Jocelyn Maragulia ◽  
Jessica Meikle ◽  
Andrew D Zelenetz
Keyword(s):  
Radiation Therapy ◽  
B Cell ◽  
Fdg Pet ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Pet Scan ◽  
Large B Cell Lymphoma ◽  
Fdg Pet Scan ◽  
Dose Dense ◽  
Large B Cell

Abstract Abstract 420 Introduction: Primary Mediastinal Large B cell lymphoma (PMBL) is a distinct subtype of diffuse large B cell lymphoma (DLBCL) that is more common in women and presents at a similar age as classical Hodgkin lymphoma (HL); and in fact gene expression profiling suggests it is more similar to HL (Blood 102: 3871–3879, 2003) than DLBCL. Patients (pts) typically present with bulky mediastinal disease and combined modality therapy (CMT) has been the mainstay of treatment; however given the risk of secondary breast cancer and coronary artery disease associated with the 36–40Gy radiation therapy to the mediastinum, programs that use chemotherapy alone are desirable provided that the favorable progression-free (PFS) and overall survival (OS) rates can be maintained. Methods: We evaluated our dose-dense R-CHOP/ICE consolidation chemotherapy program (MSKCC protocol 01–142, J Clin Oncology 28:1896-1903, 2010) for pts with PMBL. The initial 28 pts were treated on study and the subsequent 26 were treated as per protocol. No radiation therapy was permitted. All pts underwent CT and FDG-PET imaging as well as bone marrow evaluation. Therapy was administered every 2 weeks. Induction chemotherapy: four cycles of accelerated R-CHOP (rituximab 375 mg/m2; cyclophosphamide 1000 mg/m2; doxorubicin 50 mg/m2 vincristine 1.4 mg/m2 (uncapped) IVP; and prednisone 100 mg/day orally for 5 days); growth factor support was required. Consolidation chemotherapy: three cycles of ICE+/−Rituximab (J Clin Oncology 12: 3776–3785, 1999). Pt characteristics: Fifty-four pts receive treatment. Median age was 34 (range 19–59); 30 were female (56%). An elevated LDH, Karnofsky Performance Status (KPS) <80 and stage IV disease was seen in 87%, 24% and 52% respectively. Extranodal disease (ENS) was present in 74% of pts; 21 (39%) pts had lung involvement. Bulky disease defined as a mediastinal mass of at least 10 cm. was present in 36 pts (67%) of which 16 (30%) had clinical evidence of superior vena cava obstruction at presentation; the median SUV uptake in the mediastinum on the FDG-PET scan was 19. No patient had bone marrow or CNS involvement at diagnosis. Positive Immunohistochemistry markers were as follows: CD10 (6.7%), BCL6 (72.7%), BCL2 (51.2%) and MUM1 (50%). The median Ki-67 [MIB-1] expression was 60%, of which 26.7 % was ≥80%. Outcome: At a median followup for surviving pts of 3 years, the Kaplan-Meier estimates of the proportion of patients alive and progression-free are 88% and 78% respectively. Eleven pts failed therapy. Five are now progression-free after a salvage autotransplant that included radiation therapy to the mediastinum. Six pts have died; one from transplant-related mortality, one from secondary AML and 4 from PMBL, two of which had CNS disease at relapse despite intrathecal prophylaxis. None of the standard clinical or immunohistochemical risk factors predicted for PFS including: KPS (p=.79), LDH (p=.92), Stage (p=.25), ENS (p=.36), IPI (p=.18) or bulky disease (p=.42), Ki-67 [MIB-1] expression ≥80 (.34). An interim FDG-PET scan was performed on 51/54 pts; 24 (47%) of these scans were abnormal; however, this did not predict for PFS (p=.42). We also evaluated the change in SUV between the initial and interim scan with a positive cutoff of >66% (J Nucl Med 48:1626-1632, 2007) as being favorable; this also did not predict outcome (p=.21). Conclusion: This is the largest reported series of pts with PMBL treated with a uniform chemotherapy-only strategy. The MSKCC dose-dense R-CHOP/ICE program is highly effective in these pts, it avoids radiotherapy, and importantly 50% of pts who fail can be salvaged with a radiation-based transplant. Based upon these results an interim FDG-PET scan is not warranted in pts with PMBL. Disclosures: Zelenetz: GSK: Consultancy; CTI:.

scholarly journals SUVmax on Pre-Treatment FDG PET Scan Is Not Predictive of Outcome in Follicular Lymphoma after R-CHOP Threapy

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1629-1629 ◽  
Author(s):  
Mohamed Amin Ahmed ◽  
Nathan Fowler ◽  
Long Ma ◽  
Mansoor Noorani ◽  
Karishma Phansalkar ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Cell Lymphoma ◽  
Histological Grade ◽  
B Cell Lymphoma ◽  
Risk Groups ◽  
Complete Response ◽  
Pet Scan ◽  
Ki 67 ◽  
Large B Cell Lymphoma ◽  
Fdg Pet Scan

Abstract Introduction: High standardized uptake value (SUV) on FDG PET scan in follicular lymphoma (FL) suggests aggressive disease and possible transformation to diffuse large B-cell lymphoma. Schoder et al, J Clin Oncol, 2005, reported that SUV >10 predicted aggressive lymphoma with >80% certainty and SUV >13 with >90% certainty. However, it is unknown whether the maximum SUV (SUVmax) on FDG PET scan at baseline, suggesting the possibility of focal aggressive or transformed disease, has prognostic value in FL. Here, we determined the prognostic value of SUVmax on baseline FDG PET scan in patients with advanced stage FL treated uniformly with R-CHOP chemoimmunotherapy at initial diagnosis. Methods: We reviewed medical records of all patients with stage III or IV FL who had FDG PET scan at initial diagnosis and were treated with R-CHOP chemoimmunotherapy at MD Anderson Cancer Center between January 2001 and December 2012. Patients with histological diagnosis of concurrent diffuse large B-cell lymphoma were excluded. Results: For the 225 patients studied, the median age was 57 years (range, 20-82). 83 (37%) patients were >= age 60, 137 (61%) had grade 1 or 2 FL, and 88 (39%) had grade 3A (n=57, 25%) or 3B (n=31, 14%). The Ki-67 score was <=40% for 85 (60%) patients and >40% for 56 (40%) patients. FLIPI risk groups were 54 patients (24%) low, 74 (33%) intermediate, and 97 (43%) high. GELF criteria were met in 133 (59%) patients. Tumor bulk of >= 6 cm was seen in 97 (43%) patients. The absolute lymphocyte count (ALC) was normal or high in 155 (69%) patients and low in 70 (31%). Sixty-nine (31%) patients received rituximab maintenance. There was no correlation between baseline SUVmax on FDG PET scan and Ki-67 score (Pearson correlation co-efficient of 0.168). The overall and complete response rates were 96% and 87%, respectively. The median follow-up time was 66 months. At 5 years, progression-free survival (PFS) was 85% and overall survival (OS) was 90%. Male gender, stage IV, high risk FLIPI, presence of GELF criteria, high beta-2 microglobulin, and low ALC were associated with significantly inferior PFS and OS (p<0.05). Histological grade was not associated with PFS or OS. Age >= 60 was associated with inferior OS but not PFS. Rituximab maintenance was associated with improved PFS but not OS. On baseline FDG PET scan, median SUVmax was 13.7 and the SUVmax range was 1.5-42.1. 105 (47%) patients had SUVmax <=13 and 120 (53%) had SUVmax >13. Patient characteristics including age, gender, histological grade, Ki-67 score, and FLIPI risk groups were not significantly different between the two SUVmax populations (p>0.05). The overall response rates were 94% and 96% for the SUVmax <=13 and SUVmax >13 groups, respectively. The complete response rate was 87% in both groups. At 5 years, the PFS and OS were not significantly different between the low and high SUVmax groups (61% vs 63% for PFS, p=0.98 and 90% vs 89% for OS, p=0.63). PFS and OS were not significantly different even when the patients were grouped into SUVmax <=10 vs >10 (p=0.9 and 0.61, respectively) or when other cut-offs were used. SUVmax was also not predictive of PFS and OS when only the patients meeting GELF criteria were analyzed. Conclusions: In this large cohort of advanced stage FL patients treated uniformly with R-CHOP chemoimmunotherapy, SUVmax on baseline FDG PET scan was not predictive of clinical outcome or correlated with other features. It is possible that the doxorubicin-based chemotherapy regimen may have benefited patients with high SUVmax who may have underlying aggressive or undiagnosed transformed disease. It remains to be determined whether SUVmax is predictive of clinical outcome in FL patients treated with other commonly used therapies such as rituximab monotherapy, rituximab and bendamustine, or R-CVP. Figure 1 Figure 1. Disclosures Wang: Pharmacyclics, Janssen: Honoraria, Research Funding. Westin:Novartis: Research Funding.

IHP Interpretation Criteria of Interim-PET Scan Confirms Prognostic Impact In Early Stage Hodgkin Lymphoma Patients without Bulky Disease

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3890-3890 ◽  
Author(s):  
Luigi Rigacci ◽  
Pier Luigi Zinzani ◽  
Benedetta Puccini ◽  
Alessandro Broccoli ◽  
Andrea Gallamini ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Early Stage ◽  
Progression Free Survival ◽  
Pet Scan ◽  
Bulky Disease ◽  
Free Survival ◽  
Interim Pet ◽  
Interpretation Criteria ◽  
Fdg Pet Scan

Abstract Abstract 3890 Introduction: Early stage classical Hodgkin lymphoma (cHL) is highly curable with a combination of chemotherapy and radiotherapy. Nevertheless a small proportion of patients with localized stage do not respond to therapy and progressed. We want to explore the predictive value on therapy outcome of an early evaluation of treatment response by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scan performed after two corses of ABVD in pts with localized Hodgkin's disease. Patients and methods: From 2002, 246 new localized stage cHL pts were consecutively admitted to twelve Italian hematological centers on behalf of Intergruppo Italiano Linfomi. Pts with stage I-IIA according to Ann Arbor stage, independent of presence of bulky disease, were considered for the study. FDG-PET was mandatory at baseline, after two cycles and at the end of therapy. International Harmonization Project (IHP) interpretation criteria were recommended to define PET positivity. We evaluated the progression free survival of pts starting from the time of diagnosis to relapse or progression of disease or last follow-up. No treatment variation based only on PET-2 results was allowed. All bulky-disease pts reports were centrally reviewed. Results: The median age was 33 years (13-78), 133 pts were female, 225 pts were stage II, bulky was reported in 76 pts, 231pts were treated with combined modality and 15 pts were treated with chemotherapy alone. The FDG-PET performed after two cycles (PET2) was positive in 32 pts (13%). Seventeen non-bulky pts were PET2 positive: 10 (59%) progressed or relapsed and 7 remained in CR. By contrast 152/153 (99%) non-bulky pts with a negative PET2 remained in CR. Thus the PPV value of a PET2 in non-bulky pts was 59% and the NPV was 99%, moreover the sensitivity and specificity of PET2 were 91% and 96%, respectively. In bulky disease pts we performed a revision of all reports according to Deauville criteria and 3 cases were converted from PET2 positive to PET2 negative. In revised bulky disease pts 15 were PET2 positive: 6 (40%) progressed or relapsed and 9 remained in CR. In this group of pts the PPV was 40%, the NPV 93% and sensitivity and specificity were 60% and 90% respectively. In univariate analysis negative FDG-PET performed after two cycles (p .0000), absence of bulky disease at diagnosis (.005) were statistically correlated with a better progression free survival. In multivariate analysis only PET2 was independently predictive of relapse/progression probability (p .000). With a median follow-up of 35 months (range 4–87), the 2-yr FFS probability for PET2 negative and for PET2 positive non-bulky patients were 98% and 29% respectively (p: .000) for patients with bulky-disease were 99% and 45% respectively (p: .002). Conclusion: This multicentric study confirms that FDG-PET scan performed after two courses of conventional standard dose chemotherapy was able to predict treatment outcome in early stage non-bulky cHL. In bulky disease we suggest new interpretation criteria to define interim PET results. Disclosures: Vitolo: Roche: Membership on an entity's Board of Directors or advisory committees.

Is Interim/Mid-Treatment PET (interim PET, i-PET) Scan Predictive of Outcome in Diffuse Large B-Cell Lymphoma?.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2675-2675
Author(s):  
Dushyant Verma ◽  
Amol Takalkar ◽  
Runhua Shi ◽  
Glenn M. Mills ◽  
Srikanth Paladugu ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Pet Scan ◽  
Free Survival ◽  
Interim Pet ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 2675 Background: Initial treatment of diffuse large B-cell lymphoma (DLBCL) involves 6–8 cycles of chemo-immunotherapy and may be curative in 60–65% of patients. However, in the remaining patients, subsequent therapies appear inadequate for long lasting remission. A strategy to improve patient outcomes could involve early identification of patients who do not respond to treatment as expected and then employing different/aggressive treatment modalities in these patients. PET scan done during mid-treatment (interim PET, i-PET) may help identify these patients early. However, the value of i-PET in DLBCL is not established as there is controversy about its prognostic value and studies are ongoing to evaluate its benefit. Aims: To determine predictive value of i-PET on progression-free survival (PFS), overall survival (OS) in DLBCL patients. Methods: We performed retrospective analysis of DLBCL patients treated at LSU Health Shreveport, LA, between Jan 2002 – July 2012. All patients were treated with R-CHOP chemotherapy. PET-CT was performed at baseline at time of diagnosis, after 2 to 4 courses (i-PET) and at the end of therapy (final PET, f-PET). Results: Forty-four patients were evaluable for analysis. The median age was 55 years (range 21–84), 32 (73%) were males. Ann-arbor staging showed 5 patients each in stage I and II, 11 patients in stage III, 23 in stage IV, and the median IPI score was 3. Median time to i-PET was after 3 cycles of chemotherapy, and median days to i-PET after chemotherapy were 16. The median follow-up duration from start of chemotherapy was 23 months (range 4 – 89). The PET results were as follows: i-PET negative 30 (68%), i-PET positive 14 (32%) patients. Final PET results were: f-PET negative 33 (75%), f-PET positive 11 (25%) patients. The 3-year PFS was 96.3% and 35.7% for i-PET negative versus positive patients respectively (p<0.001), and the 3-year PFS for f-PET negative versus positive patients was 78.9%% versus 30.0% respectively (p<0.001). The 3-year OS was 79.4% and 62.6% for i-PET negative versus positive patients respectively (p=0.3306). The 3-year OS was 79.9% and 58.7% for f-PET negative versus positive patients respectively (p=0.021). Conclusion: Interim/mid-treatment PET (i-PET) scan is predictive of progression free survival but not overall survival for DLBCL patients. A final PET (f-PET) scan is predictive of progression free survival as well as overall survival for DLBCL patients. Larger prospective studies are needed to confirm these findings and could also look into the biology of i-PET positive patients by gene expressing profiling (GEP) and evaluate the role of novel agents in modifying the disease course. Disclosures: No relevant conflicts of interest to declare.

Primary gastric diffuse large B-cell Lymphoma (DLBCL): analyses of prognostic factors and value of pretreatment FDG-PET scan

2010 ◽  
Vol 84 (6) ◽  
pp. 493-498 ◽  
Author(s):  
Dai Chihara ◽  
Yasuhiro Oki ◽  
Shouji Ine ◽  
Harumi Kato ◽  
Hiroshi Onoda ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
B Cell ◽  
Fdg Pet ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Pet Scan ◽  
Large B Cell Lymphoma ◽  
Fdg Pet Scan ◽  
Large B Cell

Early FDG-PET Scan Confirms Its Prognostic Impact Also in Localized Stage, ABVD Treated Hodgkin Lymphoma Patients.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1450-1450
Author(s):  
Luigi Rigacci ◽  
Benedetta Puccini ◽  
Francesco Merli ◽  
Caterina Stelitano ◽  
Patrizia Pregno ◽  
...  
Keyword(s):  
Disease Progression ◽  
Fdg Pet ◽  
Early Stage ◽  
Progression Free Survival ◽  
Pet Scan ◽  
Stage I ◽  
Bulky Disease ◽  
Free Survival ◽  
Fdg Pet Scan

Abstract Background: Hodgkin’s lymphoma is one of the maligant diseases with the highest rate of cure particularly if diagnosed in early stage. Nevertheless a small proportion of patients with localized stage do not respond to therapy and become chemorefractory. FDG-PET clearly showed the high predictive value in identifing patients with bad prognosis in advanced stages. The aim of this prospective study was to evaluate the prognostic value of FDG-PET in patients with localized Hodgkin’s disease. Patients: From 2002, 122 new localized stage Hodgkin’s lymphoma patients were consecutively admitted to seven Italian hematological centers on behalf of Intergruppo Italiano Linfomi. Patients with stage I-IIA according to Ann Arbor stage, independent of presence of bulky disease, were considered for the study. FDG-PET was mandatory at baseline, after two cycles (immediately before the start of the third cycle) and at the end of therapy. We evaluated the progression free survival of patients starting from the time of diagnosis to relapse or progression of disease or last follow-up. Patients were candidate to receive 3 or 4 course of ABVD followed by involved field radiotherapy at 30 Gy, except in the cases in which physician decided to omit radiotherapy due to excess of toxicity. All patients were given the planned therapy except in case of overt progression. All patients were treated with ABVD Results: The median age was 31 years (16–75), 63 patients were female and 59 male, 10 patients presented stage I and 112 stage II, bulky was reported in 29 patients. One-hundred and ten patients were treated with combined modality (CT+RT) and 12 patients were treated with chemotherapy alone (all with 6 cycles). One hundred and eleven patients attained CR while 11 were chemoresistent: 6 showed disease progression during CT and 5 showed an early relapse. The FDG-PET performed after two cycles (PET2) was positive in 18 patients (15%) and the FDG-PET performed at the end of therapy was positive in 12 patients. Fourteen patients showed disease progression during therapy or within 6 months after having reached CR, three patients died due to the disease. In univariate analysis negative FDG-PET performed after two cycles (p .0000), absence of bulky disease at diagnosis (.003) and the use of radiotherapy (.0006) were statistically correlated with a better progression free survival. In multivariate analysis only PET2 was independently predictive of relapse/progression probability (p .007). With a median follow-up of 29 months (range 6–79) 119 patients are alive and 108 (88%) are free from progression. The 2-yr FFS probability for PET2 negative and for PET2 positive patients were 95% and 46% respectively Conclusion: This prospective and multicentric study confirms that FDG-PET scan performed after two courses of conventional standard dose chemotherapy was able to predict treatment outcome in early stage Hodgkin disease.

Primary gastric diffuse large B-cell lymphoma: The role of dose-dense chemotherapy

2018 ◽  
Vol 25 (7) ◽  
pp. 1682-1686
Author(s):  
Agustin Avilés ◽  
Maria-Jesus Nambo ◽  
Natividad Neri
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Early Stages ◽  
Large B Cell Lymphoma ◽  
Dose Dense ◽  
Large B Cell

Objective To assess if the use of a dose-dense regimen of chemotherapy can improve the prognosis in patients with primary gastric diffuse large B-cell lymphoma in early stages (I–II) but associated with worse prognostic factors. Methods One hundred and eight consecutive patients with primary gastric diffuse large B-cell lymphoma in early stages (I–II) with high serum levels of lactic dehydrogenase and beta 2 microglobulin (more than >2 of normal levels), which were associated with a worse prognostic outcome, were treated with a dose-dense chemotherapy: CHOP with increased doses of cyclophosphamide and doxorubicin, was administered every 14 days (instead of 21 days). The end points of this study were to improve outcome measured from progression-free survival and overall survival and to evaluate acute toxicities. Results Complete response was achieved in 85 patients (78%). Actuarial curves at five years show that progression-free survival was 82% and overall survival was 85%. Hematological toxicities were severe, but no death-related treatment was observed. Conclusions We considered that in this setting of patients, the use of a dose-dense regimen could be of benefit because it improves outcome and toxicities were well controlled.

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