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Richard T Hoppe - One of the best experts on this subject based on the ideXlab platform.

  • long term outcomes of patients with early stage nonbulky hodgkin lymphoma treated with combined modality therapy in the Stanford V trials the g4 and g5 studies
    International Journal of Radiation Oncology Biology Physics, 2020
    Co-Authors: Eric Mou, Ranjana H Advani, Saul A Rosenberg, Rie Von Eyben, Richard T Hoppe
    Abstract:

    Purpose Combined modality therapy (CMT) is standard therapy for early-stage Hodgkin lymphoma (ESHL). We preViously reported excellent outcomes with the abbreViated Stanford V regimen. Herein we report updated results with median follow-up >10 years on surViVal, therapy-related late effects, and impact of disease risk factors on patient outcomes. Methods and Materials The G4 and G5 studies enrolled patients with stage I-IIA nonbulky ESHL. Patients receiVed 8 weeks of Stanford V chemotherapy followed by 30 Gy modified inVolVed-field radiation therapy (mIFRT) (G4) or Stanford V-C + 20 Gy mIFRT (G5). Patients were categorized as faVorable or unfaVorable risk per German Hodgkin Study Group (GHSG) criteria and outcomes between groups compared. Results A total of 129 patients were enrolled (68 faVorable and 61 unfaVorable risk). In the G4 study (n = 87), at median follow-up of 19.7 years, 5-, 10-, and 15-year progression-free surViVal (PFS) and oVerall surViVal (OS) were 95.4%/97.7%, 91.8%/96.5%, and 91.8%/95.3%, respectiVely. In the G5 study (n = 42), at median follow-up of 13.5 years, the 5-, 10-, and 15-year PFS and OS were 92.9%/100%, 92.9%/100%, and 88.4%/91.9%, respectiVely. PFS (P = .86) and OS (P = .86) were not significantly different between studies. There were also no significant differences between studies in patients with faVorable or unfaVorable risk for PFS (F: P = .53; U: P = .96), OS (F: P = .99; U: P = .78), secondary malignancies (F: P = .74; U: P = 1.0), and cardioVascular complications (F: no cases; U: P = 1.0). Conclusions The G4 and G5 studies achieVe high rates of durable remission; 20 Versus 30 Gy mIFRT and cyclophosphamide substituted for mechlorethamine did not compromise nodal control, PFS, or OS in both faVorable and unfaVorable risk disease. These results support the efficacy of CMT in early-stage disease and lower-dose radiation therapy in patients with faVorable and nonbulky unfaVorable ESHL.

  • long term outcomes of patients with unfaVorable stage i ii classic hodgkin lymphoma treated with Stanford V chemotherapy and limited field irradiation
    Leukemia & Lymphoma, 2020
    Co-Authors: Christopher R Weil, Ranjana H Advani, Sarah E Daadi, Saul A Rosenberg, Yushen Qian, Rie Von Eyben, Karen S Corbelli, Richard T Hoppe
    Abstract:

    Management of stage I–II unfaVorable risk Hodgkin lymphoma (HL) striVes to reduce toxicity while maintaining tumor control. Compared to ABVD or BEACOPP, Stanford V chemotherapy contains less doxoru...

  • efficacy of abbreViated Stanford V chemotherapy and inVolVed field radiotherapy in early stage hodgkin lymphoma mature results of the g4 trial
    Annals of Oncology, 2013
    Co-Authors: Ranjana H Advani, Richard T Hoppe, David Baer, Joseph Mason, Roger A Warnke, J Allen, Sarah E Daadi, Saul A Rosenberg, S J Horning
    Abstract:

    Introduction To assess the efficacy of an abbreViated Stanford V regimen in patients with early-stage Hodgkin lymphoma (HL).

  • second cancers after treatment with Stanford V regimen in eastern cooperatiVe oncology group ecog pilot study e1492 at a median follow up of 17 years
    Blood, 2012
    Co-Authors: Ranjana H Advani, Nancy L. Bartlett, Richard T Hoppe, John M Bennett, Donna Neuberg, Peter A Cassileth, Brad S Kahl, Sandra J Horning
    Abstract:

    Abstract 4779 Purpose: The Stanford V regimen is a combined modality approach for treatment of Hodgkin lymphoma (HL). E1492, an ECOG pilot study, consisted of 12 weeks of Stanford V chemotherapy followed by 36 Gy radiation therapy (RT) to sites > 5 cm or macroscropic splenic disease at diagnosis. Efficacy results were reported preViously (Horning et al. J Clin Onc 18, 2000). The study now has a median follow up of 17 years and patients haVe been followed for oVerall surViVal (OS) and deVelopment of second cancers. Methods: 47 eligible patients with stage bulky mediastinal (mass > one third of the maximum intrathoracic diameter) stage I-II or stage III-IV HL were enrolled between March 1992 and February 1995. Patients were followed eVery 3 months during the first year off therapy, eVery 6 months during years 2–5 and annually thereafter. The ECOG database was reViewed for OS and reported second cancers. Patient characteristics at baseline, type of second cancer and time to deVelopment of second cancer were assessed. RT summary forms were reViewed for patients with second cancers. Results: 41 patients were treated with combined modality therapy and 6 with chemotherapy alone. The median age was 32 years (range 20–56 years). The 5 and 10 year OS are 96%, and 89% respectiVely. SeVen second cancers were reported, as shown in the Table. The cumulatiVe incidence for second cancers accounting for death as a competing risk is 0.02 (95% CI, 0–0.06) at 5 years, 0.07 (95% CI, 0–0.14) at 10 years, and 0.15 (95% CI, 0.04–0.27) at 15 years. Complete details of the exact location, histologic subtype and subsequent management of second cancers were not aVailable for reView. FiVe of the 7 cancers [2 skin, 1 prostate, 2 acute myeloid leukemia (AML)] were not radiation-related. One patient deVeloped AML after primary therapy as reported in the initial publication. A second patient deVeloped AML 5 years after salVage therapy followed by autologous stem cell transplant for relapsed HL. It is likely the 2 cases of breast cancer were treatment related. Conclusion: Within the caVeats of a retrospectiVe analysis from a small cooperatiVe group phase 2 trial, the mature 10 year OS of 89% and low frequency of secondary cancers are encouraging in comparison to historic treatment with combined modality treatment. Longer follow up of other Stanford V regimen data sets (i.e. United Kingdom National Cancer Research Institute Lymphoma Group Study ISRCTN 64141244 and the Eastern CooperatiVe Oncology Group E2496) are required to confirm these findings. Disclosures: No releVant conflicts of interest to declare.

  • patterns of failure in patients with stage i ii bulky mediastinal hodgkin lymphoma hl treated with abVd radiotherapy or the Stanford V regimen in the randomized phase iii north american intergroup trial e2496
    Blood, 2011
    Co-Authors: Ranjana H Advani, Nancy L. Bartlett, Fangxin Hong, Richard I Fisher, Randy D Gascoyne, Henry N Wagner, Leo I Gordon, Richard T Hoppe, Brad S Kahl, Patrick J Stiff
    Abstract:

    Abstract 1603 Background: We haVe preViously reported similar outcomes for patients with bulky stage I or II mediastinal HL treated with combined modality therapy either with ABVD + radiotherapy or the Stanford V regimen in the North American Intergroup trial E2496 (AdVani et al, ASH 2010 abstract 416). In the current analysis, we compare the patterns of failure between the two groups. Methods: Patients with stage I/II bulky mediastinal HL (maximum mediastinal mass width > 1/3 of intrathoracic diameter) were randomized to receiVe chemotherapy (CT) on either Arm A (ABVD x 6–8 cycles administered q 28 days) or Arm B (12 weeks of Stanford V administered weekly). Two-3 weeks after completion of chemotherapy all patients receiVed modified inVolVed field radiotherapy (RT) (36 Gy) deliVered to the mediastinum, hila, and supraclaVicular regions. Patients on Stanford V arm also receiVed inVolVed field RT to any other sites ≥ 5 cm at diagnosis. Patients were assessed 3, 6 and 12 months after completing RT with computed tomography scanning and then eVery 6 months for 5 years. The primary end points were failure free surViVal (FFS) and oVerall surViVal (OS). Disease progression was defined as 9in-field9, 9distant9 or both relatiVe to the radiation fields prescribed in the E2496 protocol. Distant sites of failure were further characterized as intra-thoracic, intra-abdominal or other (bone, bone marrow and axillae, if not preViously irradiated). Results: Two hundred and sixty-seVen patients were randomized: 136 on the ABVD arm and 131 on the Stanford V arm. Patient characteristics were well matched with no differences between two arms in oVerall response rates (ORR), FFS and OS. (AdVani et al ASH 2010 abstract 416). At a median follow up of 5.5 years 40 patients haVe relapsed with no difference in ABVD (n=18, 13%) Versus Stanford V (n=22, 17%) (p=0.49). Central reView of RT fields aVailable in 37/40 patients found major Violations with under treatment of tumor noted in 7/37 (19%). Patterns of failure are shown in Table 1. There were no differences in patterns of relapse for the two study arms. In-field relapses occurred in Conclusion: For patients with stage I/II bulky mediastinal HL, combined modality therapy with either ABVD +RT or the Stanford V regimen results in excellent disease control. In-field relapse was uncommon. These results set a benchmark for assessing ongoing trials omitting RT in patients with stage I/II bulky mediastinal HL. Future research efforts should focus on risk stratification to identify the small subset of patients who are likely to fail standard upfront therapy. US cooperatiVe group efforts in this subset of patients are ongoing that use interim PET-CT imaging based risk-adapted strategies. Disclosures: Horning: Genentech: Employment, Equity Ownership.

Ranjana H Advani - One of the best experts on this subject based on the ideXlab platform.

  • long term outcomes of patients with early stage nonbulky hodgkin lymphoma treated with combined modality therapy in the Stanford V trials the g4 and g5 studies
    International Journal of Radiation Oncology Biology Physics, 2020
    Co-Authors: Eric Mou, Ranjana H Advani, Saul A Rosenberg, Rie Von Eyben, Richard T Hoppe
    Abstract:

    Purpose Combined modality therapy (CMT) is standard therapy for early-stage Hodgkin lymphoma (ESHL). We preViously reported excellent outcomes with the abbreViated Stanford V regimen. Herein we report updated results with median follow-up >10 years on surViVal, therapy-related late effects, and impact of disease risk factors on patient outcomes. Methods and Materials The G4 and G5 studies enrolled patients with stage I-IIA nonbulky ESHL. Patients receiVed 8 weeks of Stanford V chemotherapy followed by 30 Gy modified inVolVed-field radiation therapy (mIFRT) (G4) or Stanford V-C + 20 Gy mIFRT (G5). Patients were categorized as faVorable or unfaVorable risk per German Hodgkin Study Group (GHSG) criteria and outcomes between groups compared. Results A total of 129 patients were enrolled (68 faVorable and 61 unfaVorable risk). In the G4 study (n = 87), at median follow-up of 19.7 years, 5-, 10-, and 15-year progression-free surViVal (PFS) and oVerall surViVal (OS) were 95.4%/97.7%, 91.8%/96.5%, and 91.8%/95.3%, respectiVely. In the G5 study (n = 42), at median follow-up of 13.5 years, the 5-, 10-, and 15-year PFS and OS were 92.9%/100%, 92.9%/100%, and 88.4%/91.9%, respectiVely. PFS (P = .86) and OS (P = .86) were not significantly different between studies. There were also no significant differences between studies in patients with faVorable or unfaVorable risk for PFS (F: P = .53; U: P = .96), OS (F: P = .99; U: P = .78), secondary malignancies (F: P = .74; U: P = 1.0), and cardioVascular complications (F: no cases; U: P = 1.0). Conclusions The G4 and G5 studies achieVe high rates of durable remission; 20 Versus 30 Gy mIFRT and cyclophosphamide substituted for mechlorethamine did not compromise nodal control, PFS, or OS in both faVorable and unfaVorable risk disease. These results support the efficacy of CMT in early-stage disease and lower-dose radiation therapy in patients with faVorable and nonbulky unfaVorable ESHL.

  • long term outcomes of patients with unfaVorable stage i ii classic hodgkin lymphoma treated with Stanford V chemotherapy and limited field irradiation
    Leukemia & Lymphoma, 2020
    Co-Authors: Christopher R Weil, Ranjana H Advani, Sarah E Daadi, Saul A Rosenberg, Yushen Qian, Rie Von Eyben, Karen S Corbelli, Richard T Hoppe
    Abstract:

    Management of stage I–II unfaVorable risk Hodgkin lymphoma (HL) striVes to reduce toxicity while maintaining tumor control. Compared to ABVD or BEACOPP, Stanford V chemotherapy contains less doxoru...

  • pd l1 and pd l2 genetic alterations define classical hodgkin lymphoma and predict outcome
    Journal of Clinical Oncology, 2016
    Co-Authors: Margaretha G M Roemer, Ranjana H Advani, Sarah E Daadi, Azra H Ligon, Yasodha Natkunam, Robert Redd, Heather Homer, Courtney Connelly, Heather Sun, Gordon J Freeman
    Abstract:

    PurposeClassical Hodgkin lymphomas (cHLs) include small numbers of malignant Reed-Sternberg cells within an extensiVe but ineffectiVe inflammatory/immune cell infiltrate. In cHL, chromosome 9p24.1/PD-L1/PD-L2 alterations increase the abundance of the PD-1 ligands, PD-L1 and PD-L2, and their further induction through Janus kinase 2–signal transducers and actiVators of transcription signaling. The unique composition of cHL limits its analysis with high-throughput genomic assays. Therefore, the precise incidence, nature, and prognostic significance of PD-L1/PD-L2 alterations in cHL remain undefined.MethodsWe used a fluorescent in situ hybridization assay to eValuate CD274/PD-L1 and PDCD1LG2/PD-L2 alterations in 108 biopsy specimens from patients with newly diagnosed cHL who were treated with the Stanford V regimen and had long-term follow-up. In each case, the frequency and magnitude of 9p24.1 alterations—polysomy, copy gain, and amplification—were determined, and the expression of PD-L1 and PD-L2 was eValua...

  • pd l1 and pd l2 genetic alterations define classical hodgkin lymphoma and predict outcome
    Blood, 2015
    Co-Authors: Margaretha G M Roemer, Ranjana H Advani, Sarah E Daadi, Azra H Ligon, Yasodha Natkunam, Robert Redd, Heather Homer, Courtney Connelly, Heather Sun, Bjoern Chapuy
    Abstract:

    ![Graphic][1] Introduction. Classical Hodgkin Lymphomas (cHL) include small numbers of malignant Reed-Sternberg (RS) cells within an extensiVe but ineffectiVe inflammatory/immune cell infiltrate. In cHL, chromosome 9p24.1 alterations increase the abundance of the PD-1 ligands, PD-L1 and PD-L2, and their further induction Via JAK2-STAT signaling. PD-1 ligands engage the PD-1 receptor on T-cells and induce PD-1 signaling and T-cell exhaustion. Tumor cells expressing PD-1 ligands on their surface utilize the PD-1 pathway to eVade an effectiVe immune response. In recent pilot studies, PD-1 blockade was associated with high response rates and durable remissions in relapsed/refractory cHL. The unique composition of cHL limits its analysis with high throughput genomic assays. Therefore, the precise incidence, nature and prognostic significance of PD-L1 and PD-L2 alterations in cHL remain undefined. Herein, we utilize a recently deVeloped fluorescence in situ hybridization (FISH) assay to characterize 9p24.1/ PD-L1 / PD-L2 alterations in a cohort of 108 newly diagnosed cHL patients (pts) who were uniformly treated with StanfordV (a combined modality therapy regimen) and haVe longterm followup. Methods. Pts were characterized as Ann Arbor early stage I/II faVorable risk (ES-F), early stage unfaVorable risk (bulk ≥ 10cm or ≥ .33 mediastinal dimension and/or B symptoms) (ES-U) or adVanced stage III/IV (AS). ES-F pts receiVed 8 weeks of Stanford V and 30 Gy inVolVed field radiation (IFR); ES-U and AS pts receiVed 12 weeks of Stanford V and 36 Gy IFR to initial sites > 5 cm. FISH was performed on formalin-fixed paraffin-embedded diagnostic biopsy specimens using bacterial artificial chromosome probes which coVered CD274/PD-L1 (labeled with spectrum orange) and PDCD1LG2/PD-L2 (labeled with spectrum green) and a control centromeric probe (spectrum aqua-labeled CEP9, from 9p11-q11). Malignant RS cells were identified by their nuclear morphologic features and 50 RS cells/case were analyzed. Nuclei with a target:control probe ratio of at least 3:1 were defined as amplified (amp), those with a probe ratio of more than 1:1 but less than 3:1 were classified as relatiVe copy gain, and those with a probe ratio of 1:1 but more than 2 copies of each probe were defined as polysomic for chromosome 9p. In each case, the percent and magnitude of disomy, polysomy, copy gain and amp were noted. In accordance with clinically approVed diagnostic criteria, cases were classified by the highest obserVed leVel of 9p24.1 alteration. Specifically, cases with polysomy lacked copy gain or amp and cases with copy gain lacked amp. Immunohistochemical staining for PD-L1/PAX5 was performed as preViously described and PD-L1 expression in PAX5 dim+ malignant RS cells and PAX5- infiltrating normal cells was assessed separately. Results. Almost all newly diagnosed cHL pts in this series had concordant alterations of the PD-L1 and PD-L2 loci; disomy was found in only 1% (1/108), polysomy in 5% (5/108), copy gain in 56% (61/108) and amp in 36% (39/108) of study pts. There was a correlation between intensity of PD-L1 protein expression and relatiVe genetic alterations in this series. Two additional pts had translocations of PD-L1 or PD-L2 (2%, 2/108). We next assessed the association between specific types of PD-L1/PD-L2 alterations, clinical risk factors and outcome. OVerall, the progression-free surViVal (PFS) was significantly lower for AS pts compared to ES-F/U pts (p=0.017). A model of PFS for the cHL pts by genetic alteration indicated that PFS was also significantly lower for pts with amp (p=0.02). Consistent with these findings, the incidence of 9p24.1 amp increased by clinical risk group: ES-F, 24%; ES-U, 34%; and AS, 50% (p=0.024, Kruskal-Wallis test). Therefore, we fit a full model of clinical and genetic factors including B-symptoms, bulk, stage and amp. Despite the association of amp with increased clinical risk groups, the genetic alteration further delineated PFS in the multiVariate model (p=0.075). Conclusions. PD-L1/PD-L2 alterations are a defining feature of cHL with rare polysomy and more frequent copy gain and amp. There is an increased incidence of amp in pts with AS disease and a highly significant association of PD-L1/PD-L2 amp with PFS. These findings underscore the importance of genetically defined PD-1 mediated immune eVasion in cHL and proVide a rationale for the efficacy of PD-1 blockade in this disease. Disclosures Rodig: Perkin Elmer: Membership on an entity's Board of Directors or adVisory committees; BMS: Research Funding. Shipp: BMS: Membership on an entity's Board of Directors or adVisory committees, Research Funding; Bayer: Membership on an entity's Board of Directors or adVisory committees, Research Funding; Sanofi: Research Funding; Gilead: Consultancy; Merck: Membership on an entity's Board of Directors or adVisory committees. [1]: /embed/inline-graphic-2.gif

  • outcomes in adolescents and young adults aya with hodgkin lymphoma hl treated on us cooperatiVe group protocols an adult intergroup e2496 and children s oncology group cog ahod0031 comparatiVe analysis
    Blood, 2015
    Co-Authors: Tara O Henderson, Ranjana H Advani, Fangxin Hong, Randy D Gascoyne, Susan K Parsons, Kristen Wroblewski, Lu Chen, Sonali M Smith, Jennifer L Mcneer, Louis S Constine
    Abstract:

    ![Graphic][1] Introduction: There is no clear consensus regarding the optimal therapeutic approach for AYAs with HL. Prior registry data showed that HL AYA patients treated with ABVD had similar outcomes to their older counterparts (Foltz JCO 2006). HoweVer, SEER data haVe suggested that adVances in HL surViVal among AYAs may be less robust compared with older populations (Bleyer NCI 2006). We sought to examine AYA patients treated on two recent, randomized pediatric and adult North American HL clinical trials (i.e., 17-21 years; the age group of those typically eligible for both pediatric- and adult-based HL clinical trials) by comparing outcomes of different age cohorts within E2496 as well as across the two different studies. Methods: We examined characteristics and outcomes of 114 newly diagnosed AYA HL patients aged 17-21 years treated on E2496 (ABVD Vs. Stanford V [SV] chemotherapy, Gordon JCO 2013) trial and compared the failure free surViVal (FFS) and oVerall surViVal (OS) with patients ages >21 years. In addition, we compared presenting features, planned treatment, FFS, and OS of these ECOG AYA patients with 391 newly diagnosed AYA HL patients between ages 17-21 years treated on the COG AHOD0031 (ABVE-PC backbone, Friedman JCO 2014). Unstratified and stratified log-rank tests as well as propensity score analysis were utilized to compare differences in patient outcomes. Results: In E2496, the 5-year FFS and OS rates for AYAs were 68% and 89%, respectiVely, with significant Variations identified by patient age (see Table). There was no FFS difference between ECOG AYAs treated with ABVD Vs. SV ( P =0.66). HoweVer, FFS in AYAs were inferior to those ages 21 to 44 years in E2496 ( P =0.005; see Figure, sections A and B ). Interestingly, AYA outcomes on E2496 appeared more similar to patients aged 45-59 years. In examining COG and E2496 AYA patient characteristics, there was no significant difference in sex, race, or histology. Due in part to trial design differences, a larger proportion of E2496 AYAs were stage III or IV Vs. COG AYAs (63% Vs. 29%, P <0.001) and had B symptoms (63% Vs. 27%, P <0.001); fewer E2496 patients had bulk disease (33% Vs. 77%, P <0.001). There was no significant difference in presentation with extralymphatic disease, anemia, or hypoalbuminemia. In terms of therapy, more COG AYAs receiVed radiotherapy (76% Vs. 66%, P =0.03), though in smaller doses (21 Gy Vs. 36 Gy). In each group, 3 AYAs deVeloped a second cancer. The 5-year FFS and OS for AYAs on the COG study were 80% and 97%, respectiVely ( see Figure, sections C and D ). For surViVal comparison across studies, COG AYAs appeared to haVe superior FFS compared with E2496AYAs ( P =0.001). In stratified multiVariable analyses (controlled for stage, anemia, and bulk), E2496 AYAs appeared to haVe worse FFS compared with COG AYAs in all strata except among the subgroup of patients with stage I/II without anemia. Furthermore, propensity score analysis with patients exactly matched on stage, anemia, and bulk disease confirmed the inferior FFS for E2496 AYAs compared with COG AYAs ( P =0.004). MoreoVer, the AYA surViVal disparity across studies persisted after additional coVariates were incorporated into the propensity score (i.e., age, gender, B symptoms, and hypoalbuminemia; P =0.026). Conclusions: AYA HL patients treated on E2496 had inferior outcomes compared with older patients (i.e., ages 22 to 44 years) treated within the same study, for unclear reasons, as well as to similarly matched AYA patients treated on COG AHOD0031. These outcomes may result from treatment regimen differences or dose-intensity, differing patient populations or risk profiles, biology, and/or other factors. ProspectiVe examination of these issues in AYA HL patients is warranted. | PFS | 3-yr | 5-yr | P | | ----- | ---- | ---- | ------ | | 17-21 | 70% | 68% | 0.005 | | 21-44 | 79% | 76% | | | 45-59 | 68% | 68% | | | >=60 | 56% | 48% | | | OS | P | | 17-21 | 93% | 89% | <.0001 | | 21-44 | 96% | 93% | | | 45-59 | 79% | 76% | | | >=60 | 70% | 58% | | Table 1. SurViVal Outcomes Within E2496 by Age. ![Figure 1.][2] Figure 1. Disclosures Smith: Pharmacyclics: Consultancy; Celgene: Consultancy. AdVani: Seattle Genetics, Inc.: Research Funding; Genetech: Consultancy. Horning: Genentech: Employment. Shah: Seattle Genetics: Research Funding; Rosetta Genomics: Other: Grant support; Acetylon: Other: AdVisory board; Plexus Communications: Honoraria; Pharmacyclics: Speakers Bureau; Spectrum: Other: AdVisory board, Speakers Bureau; Bayer: Honoraria; Celgene: Other: AdVisory board, Speakers Bureau; DeBartolo Institute for personalized medicine: Other: Grant support. Connors: Roche: Research Funding; Seattle Genetics: Research Funding. Leonard: Weill Cornell Medical College: Employment; Genentech: Consultancy; Medimmune: Consultancy; AstraZeneca: Consultancy; Spectrum: Consultancy; Boehringer Ingelheim: Consultancy; Vertex: Consultancy; ProNAI: Consultancy; Biotest: Consultancy; Seattle Genetics: Consultancy; Pfizer: Consultancy; Mirati Therapeutics: Consultancy; Gilead: Consultancy; NoVartis: Consultancy. Gordon: Northwestern UniVersity: Employment; Dr Leo I. Gordon: Patents & Royalties: Patent for gold nanoparticles pending. [1]: /embed/inline-graphic-2.gif [2]: pending:yes

Saul A Rosenberg - One of the best experts on this subject based on the ideXlab platform.

  • long term outcomes of patients with early stage nonbulky hodgkin lymphoma treated with combined modality therapy in the Stanford V trials the g4 and g5 studies
    International Journal of Radiation Oncology Biology Physics, 2020
    Co-Authors: Eric Mou, Ranjana H Advani, Saul A Rosenberg, Rie Von Eyben, Richard T Hoppe
    Abstract:

    Purpose Combined modality therapy (CMT) is standard therapy for early-stage Hodgkin lymphoma (ESHL). We preViously reported excellent outcomes with the abbreViated Stanford V regimen. Herein we report updated results with median follow-up >10 years on surViVal, therapy-related late effects, and impact of disease risk factors on patient outcomes. Methods and Materials The G4 and G5 studies enrolled patients with stage I-IIA nonbulky ESHL. Patients receiVed 8 weeks of Stanford V chemotherapy followed by 30 Gy modified inVolVed-field radiation therapy (mIFRT) (G4) or Stanford V-C + 20 Gy mIFRT (G5). Patients were categorized as faVorable or unfaVorable risk per German Hodgkin Study Group (GHSG) criteria and outcomes between groups compared. Results A total of 129 patients were enrolled (68 faVorable and 61 unfaVorable risk). In the G4 study (n = 87), at median follow-up of 19.7 years, 5-, 10-, and 15-year progression-free surViVal (PFS) and oVerall surViVal (OS) were 95.4%/97.7%, 91.8%/96.5%, and 91.8%/95.3%, respectiVely. In the G5 study (n = 42), at median follow-up of 13.5 years, the 5-, 10-, and 15-year PFS and OS were 92.9%/100%, 92.9%/100%, and 88.4%/91.9%, respectiVely. PFS (P = .86) and OS (P = .86) were not significantly different between studies. There were also no significant differences between studies in patients with faVorable or unfaVorable risk for PFS (F: P = .53; U: P = .96), OS (F: P = .99; U: P = .78), secondary malignancies (F: P = .74; U: P = 1.0), and cardioVascular complications (F: no cases; U: P = 1.0). Conclusions The G4 and G5 studies achieVe high rates of durable remission; 20 Versus 30 Gy mIFRT and cyclophosphamide substituted for mechlorethamine did not compromise nodal control, PFS, or OS in both faVorable and unfaVorable risk disease. These results support the efficacy of CMT in early-stage disease and lower-dose radiation therapy in patients with faVorable and nonbulky unfaVorable ESHL.

  • long term outcomes of patients with unfaVorable stage i ii classic hodgkin lymphoma treated with Stanford V chemotherapy and limited field irradiation
    Leukemia & Lymphoma, 2020
    Co-Authors: Christopher R Weil, Ranjana H Advani, Sarah E Daadi, Saul A Rosenberg, Yushen Qian, Rie Von Eyben, Karen S Corbelli, Richard T Hoppe
    Abstract:

    Management of stage I–II unfaVorable risk Hodgkin lymphoma (HL) striVes to reduce toxicity while maintaining tumor control. Compared to ABVD or BEACOPP, Stanford V chemotherapy contains less doxoru...

  • efficacy of abbreViated Stanford V chemotherapy and inVolVed field radiotherapy in early stage hodgkin lymphoma mature results of the g4 trial
    Annals of Oncology, 2013
    Co-Authors: Ranjana H Advani, Richard T Hoppe, David Baer, Joseph Mason, Roger A Warnke, J Allen, Sarah E Daadi, Saul A Rosenberg, S J Horning
    Abstract:

    Introduction To assess the efficacy of an abbreViated Stanford V regimen in patients with early-stage Hodgkin lymphoma (HL).

  • outcome of patients with adVanced hodgkin lymphoma who are either refractory to or relapsed after primary therapy with the Stanford V regimen
    Blood, 2010
    Co-Authors: Lauren S Maeda, Saul A Rosenberg, Richard T Hoppe, Sandra J Horning, Ranjana H Advani
    Abstract:

    Abstract 4828 Purpose: Stanford V is an abbreViated combined modality approach for the treatment of adVanced stage Hodgkin lymphoma (HL). This regimen was deVeloped with the aim of shortening the duration of chemotherapy, limiting the radiotherapy (RT) to a modified inVolVed field and thereby potentially reducing short and long term toxicity while maintaining or improVing cure rates. Specifically the chemotherapy regimen has significantly lower cumulatiVe doses of adriamycin, bleomycin and alkylating agents compared to other standard regimens such as ABVD or escalated BEACOPP. We haVe preViously reported excellent outcomes with this regimen with a freedom from progression (FFP) of 89% and oVerall surViVal (OS) of 96% (Horning, S.J., et al., J Clin Oncol 2002, 20:630-7). The purpose of this study was to determine the outcome of patients (pts) treated with secondary therapy after failing Stanford V. Methods: Pts with adVanced stage HL who had either refractory disease or had relapsed after primary therapy with Stanford V, were retrospectiVely identified from the HL database. We analyzed this group of patients for risk factors, salVage therapy, and treatment outcome. Results: Between May 1989 and March 2003, 167 pts were treated on protocol. At a median follow-up of 12.8 years the outcomes are excellent with a 10-year FFP and OS of 87% and 93%, respectiVely. Therapy failed in 19 pts (11%) of which 16 relapsed and 3 did not complete the intended treatment (disease progression n=2, and muscle pain and hyponatremia n=1). The median age of pts who failed therapy was 31 years (range 21 – 58) with a median time to progression of 5.1 months (range 0.2 – 41.4). 11 pts relapsed at 0 to 12 months from completion of therapy and 8 pts relapsed at > 12 months. At initial diagnosis 5 had stage I/II disease with bulky mediastinum, 5 stage III and 9 stage IV disease. The International Prognostic Score (IPS) at initial diagnosis was 0–1 (n=4), 2–3 (n=10) and 4–7 (n=5). 13/19 (68%) pts relapsed outside the RT field, 2 infield, 3 both infield and outside and 1 unknown. 7/19 pts in whom therapy failed had bulky disease and of these 5 failed outside the RT field. Relapse was detected clinically in 12 pts, and on surVeillance positron emission tomography scan performed eVery 3 to 6 months in 5 pts who were asymptomatic (2 pts unknown). 14/19 (74%) pts receiVed secondary therapy with a platinum-containing regimen (ICE or DHAP) with an oVerall response rate (ORR) of 91% (complete response [CR] n=1, partial response [PR] n=9, progressiVe disease [PD] n=1, unknown response n=3), followed by an autologous hematopoietic stem cell transplant. 5 pts were treated with non-transplant regimens consisting of chemotherapy with MOPP/ABV + RT (n=2), ChlVPP (n=1), oral cyclophosphamide (n=1) and procarbazine/alkeran/adriamycin/etoposide (n=1), with an ORR of 80% (CR n=4). Reasons for non-transplant therapy were neuropathy (n=1), pt preference (n=1), liVer disease (n=1), and unknown (n=2). 11 of the 19 pts in whom Stanford V failed died (disease progression n=3, second malignancy n=2, graft failure n=1, infection n=1, liVer failure n=1, cardiac arrest n=1, suicide n=1 and unknown n=1). At a median follow-up of 8 years, the disease-specific surViVal (DSS), FFP and OS for pts with refractory or relapsed disease after Stanford V was 84%, 63% and 42%, respectiVely. Outcome of pts who relapsed within a year was worse than pts who relapsed > 1 year with an OS of 36% Versus 50%, respectiVely. There was no difference in FFP for these groups, 64% Versus 63%, respectiVely. Conclusions: The outcome of pts with adVanced HL is excellent with the Stanford V regimen. For the 11% of pts in whom front line therapy fails, secondary therapy is effectiVe with a DSS of > 80%. The majority of pts (84%) failed at distant sites suggesting that more aggressiVe upfront chemotherapy may haVe been beneficial in these pts. Future efforts will aim at identifying this subset upfront. Pts who relapse within a year haVe a worse outcome despite salVage and for this subgroup, newer therapies are warranted. Disclosures: Horning: Genentech: Employment.

  • efficacy of abbreViated Stanford V chemotherapy and inVolVed field radiotherapy in early stage hodgkin s disease mature results of the g4 trial
    Blood, 2009
    Co-Authors: Ranjana H Advani, Richard T Hoppe, David Baer, Joseph Mason, Saul A Rosenberg, Sandra J Horning
    Abstract:

    Abstract 1670 Poster Board I-696 The standard management for early stage Hodgkin9s disease (HD) is combined modality therapy. In the G4 protocol, patients (pts) with non-bulky, supra-diaphragmatic stage I-IIA disease recei V ed 8 weeks of Stanford V chemotherapy + 30 Gy in V ol V ed field radiotherapy (IFRT). 87 pts were enrolled and treated between 4/1996 and 4/2001. Median age was 30 years (16-59) and stages were IA (n=23), IIA (n=64). UnfaVorable risk factors were present in 47 patients (54%) according to German Hodgkin Study Group (GHSG) criteria (> 2 AA sites, ESR > 50 or EN inVolVement) and 38 (44%) according to EORTC criteria (> 3 AA sites, ESR > 50). Therapy was well tolerated with grade 3-4 non-hematologic toxic eVents in 7 % of pts. These included constipation (n=3), peripheral neuropathy (n=1), generalized weakness (n=2), chest pain (n=1), mylagias (n=1), abdominal pain (n=1) and an allergic reaction to etoposide (n=1). 42 patients receiVed cytokine support for grade 3-4 neutropenia howeVer only 2 pts deVeloped feVer with neutropenia. No cases of clinical bleomycin toxicity or radiation pneumonitis were obser V ed. At a median follow-up of 9 (2-12) years, freedom from progression (FFP) and surViVal (OS) are 94% and 96% respectiVely. FFP was 100% for faVorable and 89% for unfaVorable patients by GHSG criteria (p=0.04) with no differences in OS (96.9% Versus 95.7%). All relapses (n=5) occurred in the RT field: limited in 2 patients and combined with distant disease in 3 pts. All relapses were in “unfaVorable” risk patients: 5 per GHSG and 4 per EORTC criteria. Secondary therapy included chemotherapy followed by high dose therapy and stem cell support (n=3) and ABVD (n=2). Three pts died, 2 due to disease progression after second-line therapy and one due to metastatic colon cancer. 5 patients deVeloped a second cancer (2 breast, 2 melanomas at unirradiated sites and 1 colon cancer). The cases of breast cancer were considered unrelated to RT as both occurred within 5-years of therapy in women who were > 30 yrs at time of treatment. No secondary AML and no late cardiac or pulmonary toxicities haVe been obserVed. In conclusion, for pts with non-bulky stage I/II A HD, abbreViated Stanford V with 8 weeks of chemotherapy and 30 Gy IFRT is a safe and highly effectiVe regimen. It is still too early to assess potential RT-related complications. Our outcomes in “unfaVorable” stage I-IIA patients without bulky or symptomatic disease compare faVorably with more intensiVe or prolonged regimens employed by the GHSG and EORTC. Disclosures No releVant conflicts of interest to declare.

Paolo G Gobbi - One of the best experts on this subject based on the ideXlab platform.

  • neutrophil lymphocyte ratio nlr at diagnosis is an independent prognostic factor in patients with nodular sclerosis hodgkin lymphoma results of a large multicenter study inVolVing 990 patients
    Blood, 2015
    Co-Authors: Alessia Bari, Paolo G Gobbi, Massimo Federico, Luigi Marcheselli, Tamar Tadmor, Raffaella Marcheselli, Samantha Pozzi, Angela Ferrari, Luca Baldini, Aaron Polliack
    Abstract:

    Background There is an increasing amount of data showing that tumor microenVironment, host immunity and inflammatory responses play an important role in determining the clinical course and outcome in patients with malignant lymphoma. SeVeral inVestigators haVe considered the absolute monocyte count (AMC) as a surrogate biomarker of tumor associated macrophages within the tumor microenVironment, the absolute lymphocyte count (ALC) as an important biomarker of tumor infiltrating lymphocytes, reflecting host immunity status, and the absolute neutrophil count (ANC) as indicatiVe of the systemic inflammatory response to malignancy. All the aboVe parameters haVe been suggested as significant prognostic factors in Hodgkin lymphoma (HL). The aim of the present retrospectiVe study was to Verify in whether neutrophil : lymphocyte ratio (NLR) can be utilized as an independent prognostic factor in a large cohort of patients with nodular sclerosis (NS) subtype HL. Patients and Methods This retrospectiVe analysis included data from 1017 patients diagnosed with NS HL according to the WHO criteria. We reViewed the clinical and laboratory data of consecutiVe "therapy-naiVe" patients, treated in different centers in Italy and in Israel between 1993-2012, after approVal by local institutional reView boards. Patients had receiVed different combination chemotherapy regimens : doxorubicin, bleomycin, Vinblastine and darcarbacine (ABVD), mechlorethamine, Vincristine, procarbazine, and prednisone (MOPP)/epidoxirubicin, bleomycin, and Vinblastine (EBV)/lomustine (CCNU), doxorubicin, and Vindesine (CAD), Vinblastine, bleomycin, and methotrexate (VBM), bleomycin, etoposide, doxorubicin, cyclophosphamide, Vincristine, procarbazine, and prednisone (BEACOPP) and Stanford V. The cut-off for NLR was determined from the analysis of the log (HR) as a function of NLR, using Cox cubic spline regression. The importance of the coVariate was examined using the bootstrap inclusion frequency (BIF) with log-likelihood ratio test, (cut-off of 0.05), oVer 1000 resample of hierarchical Cox PH model, where NLR was added to IPI. Progression free surViVal (PFS) and oVerall surViVal (OS) were determined by Kaplan-Meier estimates and risk groups compared using the log-rank test .We also performed Cox proportional hazard analysis. The effect size of risk was reported as a hazard ratio (HR) with the associated 95% confidence interVal (CI95). Results Of the 1017 patients, 990 (97%) had data on both IPS and NLR. Median age was 31 years (range 17-69) and 49% were males. The 5-yr PFS and OS after median follow-up of 85 months (range 1-244 months) were 81% (95CI 78-84) and 91% (95CI 89-93), respectiVely, for all patients. The log(HR) for PFS and OS Varied linearly for the function of NLR and the cut-off was selected at 6 for both outcomes. Patients with NLR >6 had a worse PFS and OS compared to NLR ≤6 (84% Vs 75% and 92% Vs 88% at 5-years, respectiVely). Figure 1). For PFS the HR for patients with NLR>6 was 1.65 (CI95 1.25-2.18, p 6 maintained it9s prognostic Value in both PFS (HR 1.49, CI95 1.12-1.98, p=0.006; with a BIF of 76%) and OS (HR 1.56, CI95 1.06-2.29, p=0.023; with a BIF of 64%). This was also eVident in continuous form for NLR both s in PFS (HR adjusted by IPS 1.02, CI95 1.01-1.04, p=0.010) and OS (HR adjusted by IPS 1.02, CI95 1.01-1.05, p=0.039). Conclusion. Although the majority of patients with HL can be cured, about 1/3 of those with adVanced stage disease relapse or progress after first line therapy. SeVeral approaches haVe been employed to recognize high risk patients, including gene expression profiling and positron emission tomography. HoweVer these procedures are expensiVe and not always easy to perform and interpret. In conclusion, despite it is retrospectiVe nature, our study shows that NLR can reliably identify high risk patients at the time of diagnosis. This easily obtainable simple prognostic parameter could well be utilized to improVe the discriminating power of the IPS score in patients with NS HL. Disclosures No releVant conflicts of interest to declare.

  • long term follow up analysis of hd9601 trial comparing abVd Versus Stanford V Versus mopp ebV cad in patients with newly diagnosed adVanced stage hodgkin s lymphoma a study from the intergruppo italiano linfomi
    Journal of Clinical Oncology, 2011
    Co-Authors: Teodoro Chisesi, Stefano Luminari, Caterina Stelitano, Alessandro Levis, Umberto Vitolo, Monica Bellei, Paolo G Gobbi, Luigi Marcheselli, Antonella Montanini, Vincenzo Pavone
    Abstract:

    Purpose The Intergruppo Italiano Linfomi HD9601 trial compared doxorubicin, bleomycin, Vinblastine, and dacarbazine (ABVD) Versus doxorubicin, Vinblastine, mechloretamine, Vincristine, bleomycin, etoposide, and prednisone (Stanford V [StV]) Versus the combination of mechlorethamine, Vincristine, procarbazine, prednisone (MOPP) with epidoxorubicin, bleomycin, Vinblastine (EBV), lomustine, doxorubicin, and Vindesine (CAD) (MOPP/EBV/CAD [MEC]) for the initial treatment of adVanced-stage Hodgkin's lymphoma to select which regimen would best support a reduced radiotherapy program (limited to two or fewer sites of either preVious bulky or partially remitting disease). Superiority of ABVD and MEC to StV was demonstrated. We report analysis of long-term outcome and toxicity. Patients and Methods Patients with stage IIB, III, or IV were randomly assigned among six cycles of ABVD, three cycles of StV, and six cycles of MEC; radiotherapy was administered in 76, 71, and 50 patients in the three arms, respectiVely. Re...

  • Bleomycin, etoposide, doxorubicin, cyclophosphamide, Vincristine, procarbazine, and prednisone outside German Hodgkin Study Group: The Italian experience
    2009
    Co-Authors: Stefano Luminari, Giuseppe Polimeno, Massimo Federico, Emilio Iannitto, Antonella Montanini, Paolo G Gobbi
    Abstract:

    Hodgkin lymphoma (HL) is one of the most treatable adult cancers, with long-term cure rates of more than 80% achieVed eVen in patients with adVanced disease.1,2 The combination of doxorubicin, bleomycin, Vinblastine, and dacarbazine (ABVD), is currently considered to be the standard treatment for HL worldwide.3 As an improVement on the ABVD combination, other regimens, including Stanford V, MOPPEBVCAD, EVA, VEBEP, and ChlVPP/ABVVP, haVe been proposed but none haVe so far been demonstrated to be more effectiVe than ABVD.4-9 In 1990, the German Hodgkin Study Group (GHSG) deVeloped a dose-escalated and accelerated combined modality regimen consisting of bleomycin, etoposide, doxorubicin, cyclophosphamide, Vincristine, procarbazine, and prednisone (BEACOPP), plus radiation therapy (RT). The HD9 trial compared cyclophosphamide, Vincristine, procarbazine, and prednisone, plus doxorubicin, bleomycin, Vinblastine, dacarbazine (COPP/ABVD) with both standard BEACOPP and escalated BEACOPP. This trial demonstrated the superiority of escalated BEACOPP, both in terms of failure free surViVal (FFS) and oVerall surViVal (OS).10 Concern about the toxicity of BEACOPP has been raised, howeVer, and further trials designed to identify a therapy with the best risk-to-benefit ratio haVe been initiated by seVeral CooperatiVe Groups. One trial by the European Organization for Research and Treatment of Cancer (EORTC) is currently recruiting and randomizes patients with adVanced HL between 4 escalated plus 4 standard courses of BEACOPP Versus 8 courses of ABVD.

  • abVd Versus modified Stanford V Versus moppebVcad with optional and limited radiotherapy in intermediate and adVanced stage hodgkin s lymphoma final results of a multicenter randomized trial by the intergruppo italiano linfomi
    Journal of Clinical Oncology, 2005
    Co-Authors: Paolo G Gobbi, Caterina Stelitano, Alessandro Levis, Umberto Vitolo, Teodoro Chisesi, G. Santini, Vincenzo Pavone, Chiara Broglia, Luigi Cavanna, Francesco Merli
    Abstract:

    Purpose In this multicenter, prospectiVe, randomized clinical trial on adVanced Hodgkin's lymphoma (HL), the efficacy and toxicity of two chemotherapy regimens, doxorubicin, Vinblastine, mechlorethamine, Vincristine, bleomycin, etoposide, and prednisone (Stanford V) and mechlorethamine, Vincristine, procarbazine, prednisone, epidoxirubicin, bleomycin, Vinblastine, lomustine, doxorubicin, and Vindesine (MOPPEBVCAD), were compared with doxorubicin, bleomycin, Vinblastine, and dacarbazine (ABVD) as standard therapy to select which regimen would best support a reduced radiotherapy program, which was limited to ≤ two sites of either preVious bulky or partially remitting disease (a modification of the original Stanford program). Patients and Methods Three hundred fifty-fiVe patients with stage IIB, III, or IV HL were randomly assigned. Three hundred thirty-four patients were assessable for the study and receiVed six cycles of ABVD (n = 122), three cycles of Stanford V (n = 107), or six cycles of MOPPEBVCAD (n =...

  • abVd Vs Stanford V sV Vs mopp ebV cad mec in adVanced hodgkin s lymphoma final results of the iil hd9601 randomized trial
    Journal of Clinical Oncology, 2004
    Co-Authors: Massimo Federico, Stefano Luminari, Umberto Vitolo, Teodoro Chisesi, A. Levis, Maura Brugiatelli, Luigi Marcheselli, Maria Goldaniga, Santo Neri, Paolo G Gobbi
    Abstract:

    6507 Background: About 30% of patients with adVanced Hodgkin's lymphoma (HL) do not respond to initial therapy with ABVD or relapse. Recently SV and MEC were reported with higher cure rates. To test the superiority of SV and MEC oVer ABVD the Intergruppo Italiano Linfomi (IIL) conducted a three arms multicentric randomized trial. Methods: Patients with adVanced stage HL (IIB-IV) and no preVious treatment were randomised to receiVe 6 courses of ABVD or 6 courses of MEC or 12 weeks of SV. At the end of chemotherapy radiotherapy was deliVered to residual masses or to the sites of preVious bulky disease. The principal end point of the study was failure free surViVal (FFS): complete response (CR) rate, Freedom From Progression (FFP) and OVerall SurViVal (OS) were secondary end-points of the study. Results: From January 1996 to April 2000, 355 pts were randomized; 23 cases were excluded due to missing data (22) or to reVised histology (1). Finally 332 (94%) patients were assessed for response and surViVal. Base...

Teodoro Chisesi - One of the best experts on this subject based on the ideXlab platform.

  • long term follow up analysis of hd9601 trial comparing abVd Versus Stanford V Versus mopp ebV cad in patients with newly diagnosed adVanced stage hodgkin s lymphoma a study from the intergruppo italiano linfomi
    Journal of Clinical Oncology, 2011
    Co-Authors: Teodoro Chisesi, Stefano Luminari, Caterina Stelitano, Alessandro Levis, Umberto Vitolo, Monica Bellei, Paolo G Gobbi, Luigi Marcheselli, Antonella Montanini, Vincenzo Pavone
    Abstract:

    Purpose The Intergruppo Italiano Linfomi HD9601 trial compared doxorubicin, bleomycin, Vinblastine, and dacarbazine (ABVD) Versus doxorubicin, Vinblastine, mechloretamine, Vincristine, bleomycin, etoposide, and prednisone (Stanford V [StV]) Versus the combination of mechlorethamine, Vincristine, procarbazine, prednisone (MOPP) with epidoxorubicin, bleomycin, Vinblastine (EBV), lomustine, doxorubicin, and Vindesine (CAD) (MOPP/EBV/CAD [MEC]) for the initial treatment of adVanced-stage Hodgkin's lymphoma to select which regimen would best support a reduced radiotherapy program (limited to two or fewer sites of either preVious bulky or partially remitting disease). Superiority of ABVD and MEC to StV was demonstrated. We report analysis of long-term outcome and toxicity. Patients and Methods Patients with stage IIB, III, or IV were randomly assigned among six cycles of ABVD, three cycles of StV, and six cycles of MEC; radiotherapy was administered in 76, 71, and 50 patients in the three arms, respectiVely. Re...

  • long term follow up analysis of hd9601 trial comparing abVd Vs Stanford V Vs moppabVcad in patients with newly diagnosed adVanced stage hodgkin lymphoma a study from the intergruppo italiano linfomi iil
    Blood, 2008
    Co-Authors: Teodoro Chisesi, Stefano Luminari, Caterina Stelitano, Alessandro Levis, Umberto Vitolo, Monica Bellei, Luigi Marcheselli, Vincenzo Pavone, Francesco Merli, Marina Liberati
    Abstract:

    PURPOSE: To proVide long term follow-up results of HD9601 trial that compared ABVD Vs MOPP-EBV-CAD (MEC) Vs Stanford V (StV) regimens for the initial treatment of patients with adVanced stage Hodgkin Lymphoma (HL) PATIENTS AND Methods: Patients with stage IIB–III or IV were eligible for randomization among 6 cycles of ABVD, 6 cycles of MEC and 12 weeks of StV; treatment had to be consolidated with optional InVolVed Field radiotherapy on Bulky or slow responding sites. For the long term, follow-up analysis study database was updated with most recent follow-up data and with information on long-term toxicity. Results: Between 1996 and 2000, 355 patients were registered into the trial and were randomly assigned to one of the three arms (ABVD 122 pts, MEC 106 pts, and StV 107 pts). Radiotherapy was administered to 62%, 47%, and 66% of cases in the 3 arms respectiVely. As preViously described response rates at the end of treatment program were 89%, 94%, and 76% in the 3 arms, respectiVely. Initial results were published in 2005 with a median f-up of 61 months. Median follow-up of current analysis is 86 months. Compared with preVious data we obserVed 2 additional relapses, both in StV arm. MoreoVer, we obserVed 7 additional deaths in patients who had achieVed a CR after initial treatment. OVerall, 20 patients died after achieVement of CR with 7 additional eVents compared with our preVious report (Gobbi et al. JCO 2007). OVerall analyzing data by study arm we obserVed 4 (+3), 11 (+3), and 5 (+1) deaths in CR patients randomized toABVD, MEC, and StV, respectiVely. Additional deaths in CR from preVious report were further analyzed and were caused by pulmonary embolism (3 cases: 2 ABVD, 1 MEC), sepsis (2 cases: 1 MEC, 1 StV), LMA (1 MEC), and second cancer NOS (1 ABVD). No additional significant longterm toxic eVent was recorded. Long-term analysis resulted in 8-yr OS of 88%, 84%, and 77% for ABVD, MEC, and StV, respectiVely without differences among study arms (P=0.337). Conclusions: The long-term analysis of HD9601 trial confirmed the results of the initial analysis. Few additional eVents obserVed were mostly represented by deaths in CR patients but these eVents did not substantially modify surViVal rates of the three arms.

  • abVd Versus modified Stanford V Versus moppebVcad with optional and limited radiotherapy in intermediate and adVanced stage hodgkin s lymphoma final results of a multicenter randomized trial by the intergruppo italiano linfomi
    Journal of Clinical Oncology, 2005
    Co-Authors: Paolo G Gobbi, Caterina Stelitano, Alessandro Levis, Umberto Vitolo, Teodoro Chisesi, G. Santini, Vincenzo Pavone, Chiara Broglia, Luigi Cavanna, Francesco Merli
    Abstract:

    Purpose In this multicenter, prospectiVe, randomized clinical trial on adVanced Hodgkin's lymphoma (HL), the efficacy and toxicity of two chemotherapy regimens, doxorubicin, Vinblastine, mechlorethamine, Vincristine, bleomycin, etoposide, and prednisone (Stanford V) and mechlorethamine, Vincristine, procarbazine, prednisone, epidoxirubicin, bleomycin, Vinblastine, lomustine, doxorubicin, and Vindesine (MOPPEBVCAD), were compared with doxorubicin, bleomycin, Vinblastine, and dacarbazine (ABVD) as standard therapy to select which regimen would best support a reduced radiotherapy program, which was limited to ≤ two sites of either preVious bulky or partially remitting disease (a modification of the original Stanford program). Patients and Methods Three hundred fifty-fiVe patients with stage IIB, III, or IV HL were randomly assigned. Three hundred thirty-four patients were assessable for the study and receiVed six cycles of ABVD (n = 122), three cycles of Stanford V (n = 107), or six cycles of MOPPEBVCAD (n =...

  • abVd Vs Stanford V sV Vs mopp ebV cad mec in adVanced hodgkin s lymphoma final results of the iil hd9601 randomized trial
    Journal of Clinical Oncology, 2004
    Co-Authors: Massimo Federico, Stefano Luminari, Umberto Vitolo, Teodoro Chisesi, A. Levis, Maura Brugiatelli, Luigi Marcheselli, Maria Goldaniga, Santo Neri, Paolo G Gobbi
    Abstract:

    6507 Background: About 30% of patients with adVanced Hodgkin's lymphoma (HL) do not respond to initial therapy with ABVD or relapse. Recently SV and MEC were reported with higher cure rates. To test the superiority of SV and MEC oVer ABVD the Intergruppo Italiano Linfomi (IIL) conducted a three arms multicentric randomized trial. Methods: Patients with adVanced stage HL (IIB-IV) and no preVious treatment were randomised to receiVe 6 courses of ABVD or 6 courses of MEC or 12 weeks of SV. At the end of chemotherapy radiotherapy was deliVered to residual masses or to the sites of preVious bulky disease. The principal end point of the study was failure free surViVal (FFS): complete response (CR) rate, Freedom From Progression (FFP) and OVerall SurViVal (OS) were secondary end-points of the study. Results: From January 1996 to April 2000, 355 pts were randomized; 23 cases were excluded due to missing data (22) or to reVised histology (1). Finally 332 (94%) patients were assessed for response and surViVal. Base...

  • ABVD Versus Stanford V Versus MEC in unfaVourable Hodgkin's lymphoma: results of a randomised trial
    Annals of Oncology, 2002
    Co-Authors: Teodoro Chisesi, Stefano Luminari, Paolo G Gobbi, Massimo Federico, A. Levis, G. Lambertenghi Deliliers, G. Santini, Maura Brugiatelli
    Abstract:

    Background: Between January 1996 and April 2000, 355 patients with adVanced Hodgkin's disease (HD) (stage II bulky disease III and IV) were enrolled in a prospectiVe, multicentre, randomised trial aimed at comparing the efficacy of two new promising regimens: Stanford V and MEC hybrid. ABVD was chosen as the control arm. Radiotherapy was planned at the end of induction therapy on residual masses or on sites of preVious bulky lesions. One hundred and seVenteen, 123 and 115 patients were treated with Stanford V, MEC and ABVD, respectiVely. The records of 275 enrolled patients (89 Stanford V, 88 MEC, 98 ABVD ) haVe been reViewed and are the subject of this report. Results: After induction therapy a complete response (CR) was obserVed in 93, 89 and 74% of patients treated with MEC, ABVD and Stanford V, respectiVely, with a statistically significant difference (P = 0.013) between the arms. After a median follow-up of 24 months, 16 relapses haVe been recorded among 196 patients who achieVed a CR. Relapse rates are 16, 6 and 4% for Stanford V, ABVD and MEC, respectiVely (P = 0.042). The 3-year surViVal was 93%, without any significant difference among the arms. HoweVer, a significant difference emerged in terms of failure free surViVal (FFS). Patients treated with Stanford V did the worst compared with those treated with ABVD or MEC (P = 0.001). Toxicity was comparable in the three treatment arms. Conclusion: For this randomised study, both ABVD and MEC gaVe superior results to Stanford V in terms of response and FFS; MEC seems to be the best regimen in terms of relapse-free surViVal, eVen if a significant difference has not yet been achieVed. Notwithstanding the short follow-up, these results seem to be Very impressiVe in defining the best standard treatment for HD for this subset of patients.