Early Stage Diffuse Large B Cell Lymphoma (DLBCL) in the CHOP-R Era: Does Involved Field Radiation Therapy (IFRT) Impact Outcome?.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3433-3433
Author(s):  
Manzurul A. Sikder ◽  
Sughosh Dhakal ◽  
Jennifer Kelly ◽  
Steven H. Bernstein ◽  
Faith Young ◽  
...  
Keyword(s):  
Early Stage ◽  
B Cell Lymphoma ◽  
Stage I ◽  
Stage Ii ◽  
Disease Stage ◽  
Event Free Survival ◽  
Bulky Disease ◽  
Free Survival ◽  
The Impact

Abstract Historically, patients (pts) with early stage DLBCL treated without consolidative IFRT more commonly relapsed in sites of initial disease. While event-free survival (EFS) was superior with IFRT after CHOP in the short-term in a large randomized trial (NEJM 339:21), prolonged follow-up demonstrated equivalent overall survival due in part to late relapses (Blood 98:724a). The optimal therapy for pts with early stage DLBCL in the rituximab-CHOP (R-CHOP) era has not been established. To determine the impact of IFRT after R-CHOP treatment on outcome of early stage DLBCL, we reviewed medical records of 67 consecutive pts with stage I and II DLBCL who were primarily treated with R-CHOP with or without IFRT between February 2001 and March 2006. Three to 8 cycles of R-CHOP were administered, and 30–45 Gy IFRT was administered for those irradiated. The Kaplan-Meier method was used for the estimates of outcome. EFS was measured from the date of diagnosis until first documented disease progression or death from any cause. Comparisons were adjusted for IPI by Cox proportional hazards regressions, and all tests were two sided. Median follow-up was 2.6 years (range 0.5–5.5). 45 (67%) of the pts were men. Median age at diagnosis was 60 years (range 20–92); 18 (27%) had ‘B’ symptoms; bulky disease (defined as mass >10cm) was present in 15 (22%); 27 (40%) had stage I and 40 (60%) had stage II disease. Stage-adjusted IPI score distribution was: IPI 0, n=6 (9%); IPI 1, n=17 (25%); IPI 2, n=24 (36%); IPI 3, n=16 (24%); IPI 4, n=4 (6%). 39 (58%) pts had extranodal disease (23% soft tissue, 21% head & neck, 56% others). As expected, since the majority of pts had more than 1 IPI risk factor, the 2-year event-free survival (EFS) was 68% (median EFS not reached). 11 (16%) pts had primary refractory disease including 3 pts who died during treatment, and they were excluded from further analysis. Of the remaining pts, 34 (61%) received IFRT, and 22 were treated with R-CHOP alone. The IPI scores of the 2 groups were balanced, but as expected, stage II disease was more common in pts who received R-CHOP alone. The EFS at 2 years for pts treated with consolidative IFRT was 87%, and with chemotherapy alone was 72%. When controlling for IPI score and the presence of bulky disease, there was a significant benefit in EFS for patients treated with R-CHOP + IFRT compared with R-CHOP alone (p=0.027). Therefore, in pts with early stage DLBCL treated with R-CHOP, we find improved outcomes with a combined modality approach including consolidative IFRT compared with chemotherapy alone as was observed in the CHOP era. Our study has inherent biases due to its retrospective nature, and limited follow-up. However, to our knowledge, this is the first study that compare R-CHOP with and without IFRT in early stage DLBCL, and therefore has important implications on future clinical trial designs.

R-CHOP compared with CHOP in patients with diffuse large B-cell lymphoma (DLCL): Russian experience

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18536-18536 ◽  
Author(s):  
I. Poddubnaya ◽  
E. Osmanov ◽  
L. Babicheva ◽  
G. Tumyan ◽  
E. Sorokin ◽  
...  
Keyword(s):  
Median Overall Survival ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Event Free Survival ◽  
Relapse Free Survival ◽  
Bulky Disease ◽  
Free Survival ◽  
Large B Cell Lymphoma

18536 Background: R-CHOP is regarded as the best available treatment for untreated patients with aggressive and indolent B- NHL. Methods: 184 previously untreated patients with DLCL were included in retrospective study: 92 patients were treated by CHOP, 92 patients were treated by CHOP plus rituximab ( R-CHOP ). Age of patients ranged 16–87 years (median 50 years). The median follow- up was 18 months. Compared groups were balanced in all parameters. The advanced stage of disease (III-IV) at diagnosis had 66% patients treated with CHOP and 67,5 % patients treated with R-CHOP. =2 extranodal zones were initially revealed at 35% in CHOP group vs 47% in R- CHOP group. PS of 25 % patients in R-CHOP group and 30% patients in CHOP group was regarded as appropriate 3–4 degrees on ECOG. Increased LDH level was marked at 60% in CHOP-group vs 54% in R-CHOP. 29% patients in R-CHOP group and 21% patients in CHOP group had B-symptoms at diagnosis; bulky disease took place in 53% cases in R-CHOP group and 62% cases in CHOP. High IPI score had 47 % patients in CHOP-group vs 48 % in R-CHOP. Results: Complete response was achieved in 74% of the patients treated with R- CHOP, as compared to 56% of those treated with CHOP alone (p<0,05). Disease progression during treatment was reported in 25% of patients in CHOP group and 18,5% in R-CHOP group. Median overall survival in patients treated with R-CHOP was NS, in patients treated with CHOP alone was 16 months. With a median follow-up of 18 months, 29 (31,5%) events (progression - 18,5%, relapse - 10%, death - 3% ) were observed in the R-CHOP group and 48 (52%) events ( progression - 25%, relapse - 20%, death - 7%) in the CHOP group (p<0,05). Median event-free survival and relapse-free survival in the CHOP group was 12 months, in R-CHOP group NS. Toxicity was equivalent in both groups. Conclusions: We have established better direct efficiency and outcome of R-CHOP in any age of pts. No significant financial relationships to disclose.

The Addition of Rituximab Eliminates the Negative Prognostic Impact of PMBCL Compared to DLBCL in Young Patients with CD20-Positive Aggressive Lymphomas Receiving a CHOP-Like Chemotherapy: Results of a Subgroup Analysis of the Mabthera International Trial Group (MInT) Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 839-839 ◽  
Author(s):  
Marek Trneny ◽  
Michael Rieger ◽  
Anders Osterborg ◽  
Ruth Pettengel ◽  
Darrell J White ◽  
...  
Keyword(s):  
Complete Remission ◽  
Subgroup Analysis ◽  
Young Patients ◽  
B Cell Lymphoma ◽  
Stage I ◽  
P Value ◽  
Prognostic Impact ◽  
Bulky Disease ◽  
Free Survival ◽  
The Impact

Abstract PMBCL is considered to be a distinct entity among diffuse large B-cell lymphoma (DLBCL). The optimal therapy is still matter of debate and the impact of the addition of rituximab to conventional chemotherapy is unknown. The aim of this subgroup analysis of the MInT study was to evaluate the effect of rituximab in PMBCL in comparison to other DLBCL with mediastinal involvement (mDLBCL). Eligible for the MInT study (Lancet Oncol2006; 7: 379–91) were patients aged 18–60 years with DLBCL who had 0–1 risk factors according to age-adjusted International Prognostic Index (IPI), stage II-IV disease, or stage I disease with bulk. Patients were randomly assigned to six cycles CHOP-like chemotherapy regimens with or without rituximab. Consolidating radiotherapy (30–40 Gy) was given to sites of primary bulky disease. Results: Of 824 patients enrolled, 87 had PMBCL and 139 mDLBCL according to nationally centralized hematopathologist review. 44 patients (51%) with PMBCL and 65 patients (47%) with mDLBCL were randomized to the rituximab arm. The subsets were balanced for IPI, but patients with PMBCL were younger (median age 35 vs 43 years); showed more frequently an elevated LDH (63% vs 33%), stage I/II disease (92% vs 65%) and bulky disease (85% vs 60%); and received more often mediastinal radiotherapy (69% vs 37%) compared with mDLBCL. Rituximab increased the rates of complete remission or complete remission unconfirmed (CR/CRu) in both subsets although this was statistically significant only for PMBCL (see Table). This was mainly due to the fact that in both subsets rituximab virtually eliminated progressive disease (PD) under primary treatment, whereas without rituximab, PD tended to be more frequent in PMBCL than in mDLBCL (24% vs 11%, p=0.09). With a median observation time of 37 months (range 0–59), estimated 3-year event-free-survival (EFS) was improved by rituximab for PMBCL (78% vs 52%, p=0.012), mDLBCL (74% vs 59%, p=0.130), and all other DLBCL (n=597, 80% vs 60%, p<0.0001). Rituximab also improved progression-free-survival (PFS) of PMBCL, but not of mDLBCL (Table). This could be explained in part by the favorable outcome of mDLBCL compared to PMBCL in the chemotherapy-only arm (3-year PFS 77% vs 64%, p=0.08). In both subsets, the overall survival (OS) benefit observed with rituximab did not reach statistical significance (Table). Multivariable cox regression models (adjusting for treatment arm; IPI; etoposide use (CHOEP21); bulky disease; histology (PBMCL vs mDLBCL); and the interactions between histology and treatment arm, and histology and IPI, respectively) identified rituximab as a strong prognostic factor and a trend to an interaction between histology and treatment arm for the outcome of a patient. Conclusion: In young patients with PMBCL, rituximab added to 6 cycles of CHOP-like chemotherapy increases response rate, EFS, and PFS to the same extent as in other DLBCL, thereby eliminating the outcome disadvantage of PMBCL observed with CHOP-like chemotherapy alone. PMBCL Rituximab CR/CRu PD 3y-EFS 3y-PFS 3y-OS No 54% (38%–70%) 24% (11%–38%) 52% (35%–66%) 64% (46%–77%) 78% (61%–88%) Yes 80% (68%–92%) 3% (0%–7%) 78% (61%–88%) 88% (70%–95%) 89% (71%–96%) P-value 0.03 0.006 0.012 0.006 0.16 mDLBCL Rituximab CR/Cru PD 3y-EFS 3y-PFS 3y-OS No 67% (55%–78%) 11% (3%–18%) 59% (46%–70%) 77% (64%–86%) 89% (79%–95%) Yes 81% (71%–91%) 2% (0%–5%) 74% (60%–83%) 81% (68%–89%) 92% (79%–97%) P-value 0.1 0.07 0.13 0.71 0.47

Predictive Value for Event-Free Survival of Interim 18F-FDG-PET In Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Treated with 6 Cycles of Dose-Dense R-CHOP-14 Immunochemotherapy Plus Pegfilgrastim as First-Line Treatment: An Open-Label Clinical Trial In Spain.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2793-2793 ◽  
Author(s):  
Eva González-Barca ◽  
Miguel Canales ◽  
María Jesús Vidal ◽  
Albert Oriol ◽  
Antonio Salar ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Predictive Value ◽  
B Cell Lymphoma ◽  
Event Free Survival ◽  
Bulky Disease ◽  
Free Survival ◽  
Interim Pet ◽  
End Of Treatment ◽  
Dose Dense

Abstract Abstract 2793 Background: DLBCL is the most frequent aggressive non Hodgkin's lymphoma in adults. The International Prognostic Index (IPI) is currently the most used tool to identify different risk patients. The role of an interim PET to early identify patients with bad response to chemotherapy is still controversial. Aims: The aim of this analysis is to evaluate the predictive value for event-free survival of an interim PET (after 2 chemotherapy cycles) and at the end of therapy (after 6 chemotherapy cycles) of dose-dense R-CHOP in patients with DLBCL. Methods: This is a prospective clinical trial for patients with DLBCL older than 65 with IPI 0–5 or younger than 65 with IPI 0–2. Treatment consists on 6 cycles of R-CHOP administered every 14 days followed by pegfilgrastim (6 mg per cycle) on day 2. In this sub-analysis we have included 69 patients who completed the 6 cycles of chemotherapy and who have PET evaluation at diagnosis, after 2 cycles of R-CHOP and at the end of treatment. All evaluations were made by combined PET/CT, except for 14 patients who were evaluated by PET alone. PET was determined to be positive or negative based on the local radiology reports. Interim PET results did not change the planned treatment. Results: 124 patients were included in the trial, 19 (15.3%) did not finish 6 cycles of treatment: 2 due to serious adverse events, 2 due to progression disease/stabilization, 7 due to investigators decision and 8 due to death. Over 105 patients who completed 6 cycles of treatment, 69 patients with complete PET evaluation (at diagnosis, after 2 cycles and at the end of treatment) were included in the analysis. Median age was 61.6 years old (range 18.2–82.8), 34 (49.3%) were older than 65 yo, 37 (53.6%) were male, 59 (85.5%) had ECOG 0–1. Characteristics of the disease at diagnosis were as follows: stage III-IV: 45 (65.2%), bulky disease: 17 (24.64%), >2 extra-nodal sites involvement: 4 (5.8%), B symptoms: 18 (26.1%), elevated LDH: 36/67 (53.7%), elevated beta-2-microglobulin: 23/62 (37.1%), IPI 3–5: 23 (33.3%). The median relative dose intensity (RDI) for cyclophosphamide and adriamycin calculated according to 3-week interval as a reference was 139.8% (≥130% in 75.2% of patients): 141.6% in younger patients and 138.6% in the elderly. Thirty-five (50.7%) patients achieved a negative PET evaluation after 2 R-CHOP cycles and 57 (82.6%) at the end of therapy. Patients with bulky disease had a positive interim PET more frequently (64.7% vs 44.2%), but most of them turned negative at the end of treatment (positive end-of-treatment PET for bulky disease: 11.7%). With a median follow-up of 28 months (limits 2.3–49), event-free survival (EFS) was 70.6% for patients with positive interim PET and 92.9% for patients with negative interim PET (p=0.14). The negative predictive value (NPV) of a negative interim PET was 94.3% and the positive predictive value (PPV) of a positive interim PET was 14.7%. EFS was 47.6% for patients with positive end-of-treatment PET and 95.6% for patients with negative end-of-treatment PET (p<0.0001). Conclusions: A negative interim PET is highly predictive of a good outcome. Patients with a positive interim PET have worse EFS (not statistically significant), but their PPV is 14.7%. Patients with bulky disease turn to a negative PET later. Although longer follow-up is needed, these results do not support early intensification of patients with DLBCL based only in a positive interim PET and, probably, other factors should be taken into account. Disclosures: No relevant conflicts of interest to declare.

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.

Concomitant Radiotherapy and Chemotherapy for Early-Stage Nasopharyngeal Carcinoma

2000 ◽  
Vol 18 (10) ◽  
pp. 2040-2045 ◽  
Author(s):  
Skye Hongiun Cheng ◽  
Stella Y. C. Tsai ◽  
K. Lawrence Yen ◽  
James Jer-Min Jian ◽  
Nei-Min Chu ◽  
...  
Keyword(s):  
Early Stage ◽  
Disease Free Survival ◽  
Stage I ◽  
Stage Ii ◽  
Free Survival ◽  
Radiotherapy Group ◽  
Radiotherapy Alone ◽  
Disease Free ◽  
Concomitant Radiotherapy

PURPOSE: Early-stage nasopharyngeal carcinoma (NPC) continues to carry a failure rate of 15% to 30% when treated with radiotherapy alone; the benefit of concomitant radiotherapy and chemotherapy (CCRT) in early-stage NPC is unclear. The purpose of this report is to describe our efforts to improve treatment outcome in early-stage NPC after CCRT. PATIENTS AND METHODS: Of 189 newly diagnosed NPC patients without evidence of distant metastases who were treated in our institution between 1990 and 1997, 44 presented with early-stage (stage I and II) disease according to the American Joint Committee on Cancer (AJCC) 1997 NPC staging system. Twelve of these patients were treated with radiotherapy alone and 32 with CCRT. Each patient’s head and neck area was evaluated by magnetic resonance imaging or computed tomography. Radiotherapy was administered at 2 Gy per fraction per day, Monday through Friday, for 35 fractions for a total dose of 70 Gy. Chemotherapy consisting of cis-diamine-dichloroplatinum and fluorouracil was delivered simultaneously with radiotherapy in weeks 1 and 6 and sequentially for two monthly cycles after radiotherapy. RESULTS: Patients who were treated with radiotherapy alone primarily had stage I disease, whereas none of those who were treated with CCRT had stage I disease (11 of 12 patients v none of 32 patients; P = .001). The locoregional control rate at 3 years for the radiotherapy group was 91.7% (median follow-up period, 34 months) and was 100% for the CCRT group (median follow-up period, 44 months) (P = .10). The 3-year disease-free survival rate in the radiotherapy group was 91.7% and was 96.9% in the CCRT group (P = .66). CONCLUSION: Our results reveal excellent prognosis of AJCC 1997 stage II NPC treated with CCRT. Stage II patients with a greater tumor burden treated with CCRT showed an equal disease-free survival, compared with stage I patients treated with radiotherapy alone. A prospective randomized trial is underway to confirm the role of CCRT in stage II NPC.

A Comparison of 3 Staging Systems for the Outcome Following Autologous Stem Cell Transplantation (ASCT) in Patients with Multiple Myeloma (MM).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5479-5479
Author(s):  
Hee-Jung Sohn ◽  
Kihyun Kim ◽  
Jae-Hoon Lee ◽  
Soo-Mee Bang ◽  
Dong Hwan Kim ◽  
...  
Keyword(s):  
Overall Survival ◽  
Gold Standard ◽  
Staging System ◽  
Stage I ◽  
Event Free Survival ◽  
Free Survival ◽  
Staging Systems ◽  
International Staging System ◽  
Beta 2 Microglobulin

Abstract The Durie-Salmon (DS) stage has been the gold standard for stratification of MM patients. However, the system does not contain beta-2 microglobulin (B2M) widely recognized as the single most powerful prognostic parameter. Recently, The Southwest Oncology Group (SWOG) staging system (Jacobson JL, et al. Br J Haematol122:441–50, 2003) and the International Staging System (ISS) (Greipp PR, et al. J Clin Oncol23:3412–20, 2005) utilizing B2M have been proposed. We aimed to evaluate whether the stage assessed at the time of ASCT by DS, SWOG, or ISS predict outcome following ASCT in patients with MM. Between November 1996 and December 2004, a total of 141 patients with MM who were treated with ASCT at 5 institutions in Korea were available for this analysis. The distribution of patients’ stage at ASCT by 3 staging systems was as Table 1. With a median follow-up of 20 months from ASCT, the median event-free survival (EFS) and overall survival (OS) were 16 months (95% confidence interval [CI], 11–21) and 56 months (95% CI, 38–74), respectively. The median survival of each stage group according to 3 staging systems at ASCT was as Table 2. Differences in EFS among the stage groups were not statistically significant. However, OS after ASCT was dependent on the SWOG stage at the time of ASCT and also significantly longer in patients with ISS stage I than others (NR vs. 39 months, P =.001). In this study, OS following ASCT was influenced by the stage according to SWOG or ISS, but not DS. The distribution of patients by 3 staging systems Stage I II III IV DS 32 (23%) 23 (16%) 86 (61%) - SWOG 53 (38%) 66 (47%) 16 (11%) 6 (4%) ISS 85 (60%) 34 (24%) 22 (16%) - Median event-free survial and overall survival by 3 staging systems Stage I II III IV P EFS=evnet-free survival, OS=overall survival, NR=not reached, * in months EFS* DS 27 17 13 - .40 SWOG 22 15 24 4 .21 ISS 17 13 10 - .63 OS* DS NR 58 40 - .17 SWOG NR 41 32 17 .045 ISS NR 32 40 - .0042

PET-CT Adapted Therapy After 3 Cycles of ABVD for All Stages of Hodgkin Lymphoma. Interim Analysis in 173 Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1772-1772
Author(s):  
Santiago Pavlovsky ◽  
Astrid Pavlovsky ◽  
Isolda Fernandez ◽  
Miguel Pavlovsky ◽  
Virginia Prates ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hodgkin Lymphoma ◽  
Progressive Disease ◽  
Cell Transplant ◽  
Advanced Stage ◽  
Event Free Survival ◽  
Bulky Disease ◽  
Free Survival ◽  
Pet Ct

Abstract Abstract 1772 Background: Hodgkin Lymphoma (HL) is the most curable type of Lymphoma with an overall survival at 5 years of 80%. ABVD can be considered as gold standard for first line treatment for all stages of HL. Dividing patients (pts.) in different prognostic groups has aimed to reduce chemo and radio toxicity in those patients with good prognosis. A negative PET-CT, either early during treatment of ABVD or after completion of it, has shown to be a powerful prognostic tool (Hutchings: Blood 2006; Gallamini: Haematologica 2006). Our cooperative group has an experience with 584 patients with HL in early or advanced stage treated with 3 or 6 cycles of ABVD plus involved field radiotherapy with a complete remission (CR) of 91% and an event free survival (EFS) and overall survival (OS) at 60 months of 79% and 95%.(S Pavlovsky, Clin Lymp My & Leuk, 2010). Aims: Test the efficacy of treatment to all stages of HL adjusted to PET-CT results after 3 cycles of ABVD. Evaluate the outcome of pts. who have a negative PET-CT after 3 cycles of ABVD and receive no further treatment. Intensify therapy only in pts. who have persistent hyper metabolic lesions in PET-CT after 3 cycles of ABVD. Method: Since October 2005, 198 newly diagnosed pts. with HL have been included in a prospective multicenter trial. Initially all patients received 3 cycles of ABVD. After the third cycle, pts. were evaluated with a PET-CT. Those pts. who achieved CR with a negative PET-CT, received no further treatment. Those with more than 50% of anatomic reduction of initial masses but persistent hyper metabolic lesions by PET-TC after 3 ABVD were considered in partial remission (PR) and completed 6 cycles of ABVD and radiotherapy (RT) on PET-CT positive areas. Those patients with less than PR after 3 cycles of ABVD received ESHAP and if CR, high doses of chemotherapy and an autologous stem cell transplant (ASCT). All patients were re-evaluated at the end of treatment. The median follow up is of 30 months (3-62). Results: One hundred and seventy three patients completed three cycles of ABVD followed by a PET-CT. The median age at diagnosis was 29 years. One hundred and thirty-six (79%) had localized stage (I-II) at diagnosis and 37 (21%) presented with advanced stage (III-IV). Of 155 pts. 77 (50%) pts had IPS 0–1, 66 (43%) had IPS 2–3 and 12 (8%) had IPS 4–5. Twenty six (17%) pts. had bulky disease at diagnosis. One hundred and thirty-seven (79%) pts. achieved CR with negative PET-CT after 3 cycles of ABVD. Thirty-six (21%) were PET-CT positive, of them 32 pts achieved PR and completed a total of 6 cycles of ABVD plus RT in hyper metabolic lesions. Twenty five achieved CR (72%), 5 persisted with PR and 2 died of progressive disease. Four pts showed progressive disease (PD) after 3 ABVD and received ESHAP and ASCT, 2 achieved and remained in CR, 1 is in PR and 1 died of progressive disease. Of 173 pts who completed treatment with ABVD × 3 cycles, ABVD × 6 cycles plus RT on PET-TC positive areas or ESHAP plus ASCT, 164 pts (95%) achieved CR. Of these 164 pts., 14 pts (8%) relapsed. The EFS and OS at 36 months is 83% and 97% respectively. Patients with early negative PET-TC have an event-free survival of 87% compared to 62% (P=0,001) for pts with early positive PET CT. The OS at 36 months was 100% versus 86% respectively (<0.001). Conclusion: Treating patients with ABVD, evaluating response after 3 cycles with PET-CT, and adapting further therapy, leads to a high rate of CR avoiding more aggressive chemotherapy and radiotherapy. Three courses of ABVD without RT are adequate in patients with early CR defined by negative PET-CT. In early positive PET-CT it is possible to intensify therapy improving the otherwise bad prognosis; more aggressive treatment might also be suitable. These results need to be confirmed by a larger group of patients and a longer follow-up. Disclosures: No relevant conflicts of interest to declare.

IPI24: An International Study To Create An IPI For The Event-Free Survival At 24 Months (EFS24) Endpoint For DLBCL In The Immunochemotherapy Era

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 362-362 ◽  
Author(s):  
Matthew J Maurer ◽  
Herve Ghesquieres ◽  
Jean-Philippe Jais ◽  
Thomas E Witzig ◽  
Corinne Haioun ◽  
...  
Keyword(s):  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
Individual Risk ◽  
Parameter Estimates ◽  
Newly Diagnosed ◽  
Event Free Survival ◽  
Bulky Disease ◽  
Free Survival ◽  
Clinical Variables ◽  
Ecog Ps

Abstract We have recently reported that event-free survival at 24 months from diagnosis (EFS24) is a robust endpoint for assessment of disease related outcome for newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL) treated with anthracycline-based immunochemotherapy (IC). Patients who achieve EFS24 following IC have a subsequent overall survival that is equivalent to the age and sex matched general population. The IPI was developed in the pre-rituximab era using OS/EFS endpoints. While the IPI is associated with outcome in the IC era, the original survival estimates for the IPI risk groups are outdated. The IPI is also a discrete risk classifier, with only 6 possible groups. Here we remodel the IPI using EFS24 as the endpoint in a large international cohort of patients treated with IC. This model provides an individual level 0-100% risk of failing to achieve EFS24 for each patient and can be used for patient prognosis, treatment stratification, and risk assessment. Methods Newly diagnosed DLBCL patients treated with immunochemotherapy from the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource, NCCTG N0489 clinical trial, GELA LNH2003B program, and a Lyon, France based hospital registry were included in the original EFS24 study. Patients with a relapse, progression, unplanned re-treatment, or death due to any cause within 730 days of diagnosis were considered a failure for the EFS24 endpoint. Patients alive and progression/relapse free at 730 days from diagnosis with no subsequent treatment following initial IC were considered a success for the EFS24 endpoint. Variables selected for potential model inclusion were the IPI components (age, stage, ECOG PS, number of extranodal sites, and LDH), as well as standard clinical variables typically reported in studies of DLBCL: presence of B-symptoms, bone marrow involvement, bulky disease (>10 cm), and sex. The IPI24, a prognostic model for EFS24, was developed using logistic regression models. Model building began by fitting the classic IPI score (0-5), then allowing individual IPI variables to carry different model weights and number of categories, followed by dropping insignificant variables, finally adding any additional significant variables. Model performance was assessed using bias corrected c-statistics, AIC, and R2 values. Model selection was done using the complete case set with multiple imputation on the full dataset used to refine parameter estimates for the final model. Results 1596 total patients were available for modeling. The median age was 62 (range 18-93) and 53% were male; 33% were IPI 0-1, 25% were IPI 2, 25% were IPI 3, and 17% were IPI of 4-5. The failure rate for achieving EFS24 was 29%. All variables but sex (p=0.33) were univariately associated with EFS24 (p<6.4x10-5). The original IPI had good prognostic ability for EFS24 (c=0.696, p=2.2x10-32). Allowing multiple categories for ECOG PS, stage, and age (continuous) improved model fit and prognostic ability (c=0.727). The number of extranodal sites was not significant when IPI variables were modeled separately and was removed from the model. Sex and bulky disease were additional significant variables when added to the model. Thus, the final IPI24 model contained the following risk predictors: male sex, ECOG PS (0 vs. 1 vs 2 vs 3-4), stage (I vs. II, vs. III vs. IV), LDH (elevated vs. normal range), bulky disease > 10cm, and age (continuous). This model resulted in improved fit and prognostic ability (c=0.749) over the standard IPI (c=0.696, bootstrap p<0.001). Model validation was performed on an additional 158 patients from the SPORE MER and showed good concordance (c=0.697). Additional validation is planned in a larger set of independent patients. Conclusion The IPI24, generated using standard clinical variables, yields an individual risk prediction for failing to achieve EFS24 following IC for treatment of DLBCL. The IPI24 has superior prognostic ability to the standard IPI and can be implemented in the clinic using a nomogram or as a simple electronic application. Disclosures: No relevant conflicts of interest to declare.

Primary Splenic Diffuse Large B-Cell Lymphoma (PS-DLBCL): Splenectomy Improves Survival

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4439-4439 ◽  
Author(s):  
Osnat Bairey ◽  
Lev Shvidel ◽  
Chava Perry ◽  
Eldad J Dann ◽  
Rosa Ruchlemer ◽  
...  
Keyword(s):  
Overall Survival ◽  
Performance Status ◽  
B Cell Lymphoma ◽  
Stage I ◽  
Event Free Survival ◽  
Ecog Performance Status ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
The Mean ◽  
Ecog Ps

Abstract Introduction: Although the spleen is involved in about a third of patients with non-Hodgkin's lymphoma (NHL), primary splenic diffuse large B-cell lymphoma (PS-DLBCL) is rare having a reported incidence of less than 1% of all NHL. Most of the described series include small numbers of patients before the rituximab era and the role of splenectomy treatment in addition to immuno-chemotherapy is unknown. Methods: Data were retrospectively collected for 87 patients (pts) with PS-DLBCL treated in 7 medical centers in Israel during the years 1982-2013. Patients presenting with systemic disease with splenic involvement or those having a diagnostic biopsy from other nodal or extranodal disease were excluded. Results: The mean age was 59.6 years (range, 24-89 years); 57.5% were male. Abdominal pain was reported in 61 pts (81%), B symptoms in 49 pts (59%), ECOG performance status 0 - 1 in 85%. Stage I disease was recorded in 28%, II in 33%, III in 18%, and IV in 21%. Thrombocytopenia (<100,000/µl) was recorded in only 6 pts. Lactic dehydrogenase levels (LDH) were elevated in 69 pts (84%). Favorable International Prognostic Index (IPI) 0-2 was recorded in 62 pts (72%). The mean splenic length was 17.34±6 cm (range 7- 37 cm) and the mean splenic weight was 1216 gm±1243 gm (range 180-6000 gm). A splenic mass was found in 97% of pts, and its mean size was 9.26 cm (range 3-18 cm). The diagnostic procedure was core needle biopsy in 46 pts and splenectomy in 39 pts: 27 underwent open splenectomy and 12 laparoscopic splenectomy. Splenectomized pts had lower IPI (p<0.05) and lower stage (p<0.05) compared to non-splenectomized pts. Treatment: The CHOP regimen was given to 80 pts (92%), DA-EPOCH was given to 2 pts (2%) and 5 pts (6%) received other regimens. Rituximab was given to 68 pts (78%). Complete response was achieved in 67 pts (80%) and partial response in 8 (9%). Relapse occurred in 17 pts (22%). Survival: The median follow-up time was 7 years (range 0-19.4 years). During this period 24 pts died (27.5%). The 5-year overall survival (OS) was 76.6±4.9% and 5-year event-free survival (EFS) 67.2±5.5%. Splenectomy at diagnosis improved survival: the 5-year EFS was 85.4±6% and 54.7±8% for splenectomized and non-splenectomized pts respectively (p=0.02) and the 5-year OS was 91.2±5% and 67.9±7% respectively (p=0.08). For the 53 pts with stage I-II disease, both 5-year EFS and OS were better in the splenectomized pts (p<0.02, Fig 1). The 5-year EFS and OS in pts with stage I and II disease that were splenectomized at diagnosis was 89.6±6% and 96.4±3.5% as compared with 50.5±11% and 63.2±11% in pts who were not splenectomized (p=0.012 and 0.009). The EFS and OS were not influenced by the stage of the disease. Overall survival was associated with B symptoms (p=0.02), weight loss (p=0.04) and ECOG performance status (p=0.03). In a multivariate model, low ECOG PS and splenectomy independently predicted a better EFS (p=0.03 and 0.02 respectively), however for OS, low ECOG PS independently predicted better OS (p=0.03), while splenectomy had only marginal effect on the OS (p=0.056). Conclusions: In our group of pts, PS-DLBCL generally presented with abdominal pain, high LDH and a splenic mass. We demonstrate for the first time that splenectomy at diagnosis improves survival in early stages of PS-DLBCL. Our study is a retrospective one. Therefore, until prospective studies prove that early splenectomy in PS-DLBCL is beneficial in terms of overall survival, the risk and benefit of performing splenectomy should be weighed for each patient. Fig 1: (A) Event-free survival and (B) Overall survival in patients with primary splenic DLBCL and stages I - II disease who did or did not undergo splenectomy at diagnosis. Fig 1:. (A) Event-free survival and (B) Overall survival in patients with primary splenic DLBCL and stages I - II disease who did or did not undergo splenectomy at diagnosis. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

FEC 60 adjuvant chemotherapy (AdCT) in breast cancer (BC) patients (Pts): 10-year follow-up results

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10725-10725 ◽  
Author(s):  
F. Moura Silva ◽  
C. Tosello ◽  
M. T. Laloni ◽  
C. M. Andrade ◽  
A. Bertozzi ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Stage I ◽  
Stage Ii ◽  
Pathological Stage ◽  
Anticancer Effect ◽  
Free Survival ◽  
Metastatic Sites ◽  
To Receive ◽  
Disease Free

10725 Background: To evaluate the efficacy of the Epirubicin as a part of the FEC60 AdCT in operable BrC patients in a Brazilian single-center. Methods: We verified retrospectively our experience with FEC 60 as AdCT in pre and postmenopausal, node positive and negative, pathologic stage I, II and III patients with BrC. Pts were submitted after surgery to receive Fluorouracil 600 mg/m2, Epirubicin 60 mg/m2 and Cyclophosphamide 600 mg/m2 every 28 days for 6 cycles. Pts who were ER+ and/or PR+ received Tamoxifen (TMX) 20 mg/day for 5 years after AdCT. Radiotherapy was also offered at the end of AdCT if indicated. All patients were evaluated in terms of 10 year (y) Disease Free Survival (DFS) and Overall Survival (OS). The most common toxicities (acute and chronic) and metastatic sites will also be reported. Results: Between July 1983 and December 1995 a total of 752 patients (ranging from 22 to 77 years old - median 47.7) were encountered and all of them were evaluated to 10 year (y) DFS and OS. Approximately 61% of these patients received adjuvant TMX. Pts in premenopausal and postmenopausal represented 62.5% and 37.5% respectively. 72 (11%) pts had pathological stage I; 353 (46%) pts had stage II and 327 (43%) had stage III. The 10y DFS was 70%, 46% and 19% for stage I, II and III respectively. The 10y OS after a minimal follow-up of 122.98 months was 74%, 48% and 20% for stage I, II and III respectively. Conclusions: Our results demonstrated that FEC 60 regimen is active and well tolerated in the adjuvant treatment for BrC pts. We had about 89% of stage II and III pts and in this population FEC60 regimen add benefit. Nevertheless, the randomized studies indicate that the greatest anticancer effect of Epirubicin requires doses ranging from 75 to 120 mg/m2, but due to economic reasons (we integrate the brazilian public healthy system) we could not offer dosages greater than 60 mg/m2. FEC 60 was feasible and offered reasonable results in our population in terms of 10y DFS and OS. No significant financial relationships to disclose.

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