Eight cycles of BEACOPP escalated compared with 4 cycles of BEACOPP escalated followed by 4 cycles of BEACOPP baseline with or without radiotherapy in patients in advanced stage Hodgkin lymphoma (HL): Final analysis of the HD12 trial of the German Hodgkin Study Group (GHSG)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8544-8544 ◽  
Author(s):  
V. Diehl ◽  
H. Haverkamp ◽  
R. Mueller ◽  
H. Mueller-Hermelink ◽  
T. Cerny ◽  
...  

8544 Background: The GHSG HD9 trial had established BEACOPP escalated (BE) as new standard of care for advanced-stage HL patients. The successor study, HD12, evaluated a possible reduction in toxicity by comparing 8 cycles of BE with 4 cycles BE followed by 4 cycles BB. The second question in this trial related to the need of additional radiotherapy (RT) to initial bulk and residual disease. Methods: HL patients in stage IIB with large mediastinal mass and/or E-lesions or stage III/IV were randomised according to a 2x2-factorial design between: 8BE + RT, 8BE no RT, 4BE+4BB + RT, 4BE+4BB no RT. Primary endpoint of the trial was FFTF. Between 9/1999 and 1/2003, a total of 1,670 patients aged 16–65 were randomized. For this final analysis at a median follow up of 78 months, 99 patients were excluded for various reasons resulting in 1,571 eligible patients. Results: Patient characteristics in the 4 groups were comparable. Treatment-related toxicity of WHO grade III/IV was observed in 97% of patients. Most prominent differences between pooled chemotherapy arms were anemia (65% 8BE vs 51% 4BE+4BB) and thrombopenia (65% vs 51%). Treatment outcome: complete remission 92.4%; early progression 2.2%; progression/relapse 7.8% (6.6% and 8.5%). A total of 156 (9.9%) deaths (72 vs 84) have been observed (22 vs 32 acute or salvage treatment toxicity; 15 vs 24 HL; 22 vs 13 secondary neoplasia). Most treatment related deaths occurred in the >60 years age group, the first 4 cycles and the IPS> 3 RF groups. Secondary neoplasias were observed in 77 patients (4.9%). At 5 years, OS was 91%, FFTF 85.5% and progression free survival (PFS) 86.2% (Kaplan-Meier estimates). Estimates for the difference at 5 years are 1.8% for OS, 2.3% for FFTF and 2.7% for PFS favoring BE. However, there was no statistical difference between 8x BE and 4BE+4BB in all outcome parameters (p>0.19, log rank test). There is also no significant difference between the RT or no-RT arms in this study. Conclusions: The adoption of 4BE+4BB as a new standard in the future GHSG studies will depend on a refined analysis of the total data set and will be presented. No significant financial relationships to disclose.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1558-1558 ◽  
Author(s):  
Volker Diehl ◽  
Heinz Haverkamp ◽  
Rolf Peter Mueller ◽  
Hans Theodor Eich ◽  
Hans Konrad Mueller-Hermelink ◽  
...  

Abstract Purpose: The GHSG HD9 trial had established BEACOPP escalated (BE) as new standard of care for advanced-stage HL patients by showing significant superiority in terms of failure-free survival (FFTF) and overall survival (OS) over COPP/ABVD and BEACOPP baseline (BB) (each 8 cycles). The successor study, HD12, evaluated a possible reduction in toxicity by comparing 8 cycles of BE with 4 cycles BE followed by 4 cycles BB. The second question in this trial related to the need of additional radiotherapy (RT) to initial bulk and residual disease. Patients and methods: HL patients in stage IIB with large mediastinal mass and/or E-lesions or stage III/IV were randomised according to a 2×2-factorial design between: 8BE + RT, 8BE no RT, 4BE+4BB + RT, 4BE+4BB no RT. Reviewing CT-images before and after chemotherapy treatment, fields for RT were centrally planned by a multidisciplinary diagnostic panel blinded for the randomisation arm. Primary endpoint of the trial was FFTF. Between 9/1999 and 1/2003, a total of 1,670 patients aged 16–65 were randomized. For this final analysis at a median follow up of 78 months, 99 patients were excluded (42 HL not confirmed, 20 revision of stage, 20 no study treatment or documentation, 17 others) resulting in 1,571 eligible patients. Results: Patient characteristics in the 4 groups were comparable with 49% of patients in stage III, 35% in stage IV, 68% reporting B-symptoms and 28% having a large mediastinal tumor. An IPS of 3 or greater was reported for 38% of patients, predominant histology was nodular sclerosis with 57% of cases. Treatment-related toxicity of WHO grade III/IV was observed in 97% of patients. Most prominent differences between pooled chemotherapy arms were anemia (65% 8BE vs 51% 4BE+4BB) and thrombopenia (65% vs 51%). Treatment outcome: complete remission 92.4%; early progression 2.2%; progression/relapse 7.8% (6.6% and 8.5%). A total of 156 (9.9%) deaths (72 vs 84) have been observed (22 vs 32 acute or salvage treatment toxicity; 15 vs 24 HL; 22 vs 13 secondary neoplasia). Most treatment related deaths occurred in the >60 years age group, the first 4 cycles and the IPS> 3 RF groups. Secondary neoplasias were observed in 77 patients (4.9%): AML/MDS 1.5% vs 1.4%, NHL 1.4% vs 0.6% and solid tumors/others 2.5% vs 2.3%. At 5 years, OS was 91%, FFTF 85.5% and progression free survival (PFS) 86.2% (Kaplan- Meier estimates). Estimates for the difference at 5 years are 1.8% for OS, 2.3% for FFTF and 2.7% for PFS favoring BE. However, there was no statistical difference between 8x BE and 4BE+4BB in all outcome parameters (p>0.19, log rank test). There is also no significant difference between the RT or no-RT arms in this study with the caveat that a number of high-risk patients receiving RT based on the blinded panel decision. Conclusion: The adoption of 4BE+4BB as a new standard in the future GHSG studies will depend on a refined analysis of the total data set and will be presented.


Blood ◽  
2018 ◽  
Vol 132 (20) ◽  
pp. 2154-2165 ◽  
Author(s):  
Michael A. Chapman ◽  
Jonathan Sive ◽  
John Ambrose ◽  
Claire Roddie ◽  
Nicholas Counsell ◽  
...  

Abstract Improving outcomes in multiple myeloma will involve not only development of new therapies but also better use of existing treatments. We performed RNA sequencing on samples from newly diagnosed patients enrolled in the phase 2 PADIMAC (Bortezomib, Adriamycin, and Dexamethasone Therapy for Previously Untreated Patients with Multiple Myeloma: Impact of Minimal Residual Disease in Patients with Deferred ASCT) study. Using synthetic annealing and the large margin nearest neighbor algorithm, we developed and trained a 7-gene signature to predict treatment outcome. We tested the signature in independent cohorts treated with bortezomib- and lenalidomide-based therapies. The signature was capable of distinguishing which patients would respond better to which regimen. In the CoMMpass data set, patients who were treated correctly according to the signature had a better progression-free survival (median, 20.1 months vs not reached; hazard ratio [HR], 0.40; confidence interval [CI], 0.23-0.72; P = .0012) and overall survival (median, 30.7 months vs not reached; HR, 0.41; CI, 0.21-0.80; P = .0049) than those who were not. Indeed, the outcome for these correctly treated patients was noninferior to that for those treated with combined bortezomib, lenalidomide, and dexamethasone, arguably the standard of care in the United States but not widely available elsewhere. The small size of the signature will facilitate clinical translation, thus enabling more targeted drug regimens to be delivered in myeloma.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16524-e16524
Author(s):  
Catherine Kendall Major ◽  
Michael Brandon Williams ◽  
Mark T. Fleming

e16524 Background: The standard of care for MIBC is neoadjuvant (NAC) cisplatin-based chemotherapy with either 3-4 cycles of dose dense MVAC or 4 cycles of gemcitabine/cisplatin (GC) followed by radical cystectomy. However, due to toxicity some patients are unable to complete intention to treat full course chemotherapy. We aim to identify any variation in overall survival (OS) and progression-free survival (PFS) with 3 vs 4 cycles of neoadjuvant GC in the setting of miUCB. We hypothesize that there will be a statistically significant difference in OS and PFS with three vs four cycles of neoadjuvant GC. Methods: A consecutive retrospective chart review of patients with MIBC treated with three or four cycles of neoadjuvant cisplatin-based chemotherapy from 2009-2020 was performed. R Studio was used to generate Kaplan-Meier curves representing OS and PFS with p-values. Results: One hundred and twenty-one patients were identified. Patient characteristics are described in the table below. Eighty-six patients received 4 cycles of GC and thirty-five patients received 3 cycles. Ninety-five patients proceeded to cystectomy: 93 received a radical cystectomy, 1 received a partial cystectomy, and 1 was aborted due to positive lymph nodes. There was a statistically significant difference in OS between those who got 3 or 4 cycles (p=0.03) and PFS (p=0.014). Median OS for those who got 3 cycles and 4 cycles was 52 months and 92 months respectively. Conclusions: Toxicity can preclude patients from receiving four cycles of GC and this study demonstrates a significant difference in overall OS and PFS between those who receive 3 vs 4 cycles of GC.[Table: see text]


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 716-716 ◽  
Author(s):  
Andreas Engert ◽  
Volker Diehl ◽  
Annette Pluetschow ◽  
Hans T. Eich ◽  
Richard Herrmann ◽  
...  

Abstract Abstract 716 Background: There has been an ongoing debate on the best treatment for patients with early favourable Hodgkin lymphoma (HL). Open questions include the choice between combined modality treatment or chemotherapy only, the number of chemotherapy cycles needed and the optimal radiation dose. The GHSG thus conducted a randomized study for patients with early-stage favourable Hodgkin lymphoma (HD10) in which these questions were addressed. Methods: HD10 was an international prospectively randomized multicenter trial comparing 2 and 4 cycles of ABVD as well as 20Gy or 30Gy involved field radiotherapy (IFRT) in a 2 × 2 statistical design. Between 5/1998 and 1/2003, a total of 1370 patients from 329 centers were randomized into four arms: 4 × ABVD + 30Gy; 4 × ABVD + 20Gy; 2 × ABVD + 30Gy; 2 × ABVD + 20Gy. All patients had their initial histology reviewed by a lymphoma expert panel. Documentation was complete in more than 99,1% of cases for this final analysis. Results: Patients were equally balanced for age, gender, stage, histology, performance status and risk factors between arms. There were significant differences in major toxicity (WHO grade III/IV) between 4 × ABVD and 2 × ABVD in the overall number of events (52% vs 33%) including leukopenia (24% vs 15%) and hair loss (28% vs 15%). In terms of radiation dose, there also was a difference in toxicity between 30Gy and 20Gy IFRT (all events: 8.7% vs 2.9%), dysphagia (3% vs 2%), mucositis (3.4% vs 0.7%). Complete remission was achieved in 97% of patients treated with 4 × ABVD, 97% with 2 × ABVD, 99% after 30Gy and 97% after 20Gy. With a median follow-up of 79–91 months, there was no significant difference between 4 × ABVD and 2 × ABVD in terms of overall survival at 5 years (OS: 4 × ABVD 97.1%; 2 × ABVD: 96.6%), freedom from treatment failure (FFTF: 93.0% vs 91.1%) and progression free survival (PFS: 93.5% vs 91.2%). For the radiotherapy question, there were also no significant differences between patients receiving 30Gy IFRT and those with 20Gy IFRT in terms of OS (97.6% vs 97.5%), FFTF (93.4% vs 92.9%) and PFS (93.7% vs 93.2%), respectively. Importantly, there was also no significant difference in terms of OS, FFTF and PFS when all four arms were compared. Conclusion: Two cycles of ABVD followed by 20Gy IFRT is the new GHSG standard of care for Hodgkin patients in early favourable stages. Disclosures: No relevant conflicts of interest to declare.


2010 ◽  
Vol 28 (18_suppl) ◽  
pp. LBA5008-LBA5008 ◽  
Author(s):  
M. G. Teneriello ◽  
A. N. Gordon ◽  
P. Lim ◽  
M. Janicek

LBA5008 Background: Safety and efficacy of GC or TC induction followed by elective T consolidation (Tcon) were evaluated. Methods: Patients (pts) with stage IC-IV epithelial OC were randomized to GC: G 1,000 mg/m2 on days 1, 8 plus C AUC=5 on day 1; or TC: T 175 mg/m2 plus C AUC=6 on day 1 for a total of six 21-day cycles. Pts with a complete response (CR) could receive Tcon 135 mg/m2every 28 days for 12 cycles. Non-CR pts received single-agent crossover (CO) therapy (CO-T 175 mg/m2 on day 1 or CO-G 1,000 mg/m2 on days 1, 8) every 21 days until CR or progression of disease (PD). PD or death in 636 pts was required to compare GC and TC with 80% power for progression-free survival (PFS), the primary endpoint. Efficacy results were compared by log-rank test. Results: The trial was stopped in 8/2009 after an ad hoc futility analysis showed low probability of a positive PFS result. Of 919 pts enrolled, 88 pts were excluded (clerical errors); 831 pts were entered; 820 pts had induction; 352 pts had Tcon (GC-Tcon=169, TC-Tcon=183); 155 pts had crossover (CO-T=77, CO-G=78); 313 pts discontinued after induction (GC=165, TC=148). Baseline pt characteristics were balanced across arms. Overall response and adverse events for induction regimens were similar to interim results (Gordon, Clin Ovar Cancer, 2009). For GC and TC, median PFS were 20.0 and 22.2 months; median overall survival (OS) were 43.8 and 57.3 months, respectively. There was no significant difference in PFS (p=0.199) comparing GC and TC. Despite high censorship (GC: 52.8%, TC: 61.4%), OS was greater for TC (p=0.013) compared to GC, but there was no statistical difference after adjusting for significant covariates. For pts with CR, median OS was 65.6 months with Tcon versus 51.4 months without Tcon (p=0.041). Median OS was not reached for TC-Tcon and was 56.1 months for GC-Tcon (p=0.035). For pts not receiving Tcon or receiving either CO-T or CO-G crossover, there was no difference in OS. Conclusions: PFS was similar for GC and TC. Tcon improved OS. However, OS analysis was limited by study design and high censorship. GC does not offer an advantage over standard of care TC for first-line chemotherapy in advanced OC. No significant financial relationships to disclose.


2010 ◽  
Vol 113 (5) ◽  
pp. 1029-1035 ◽  
Author(s):  
Michael E. Sughrue ◽  
Ari J. Kane ◽  
Gopal Shangari ◽  
Martin J. Rutkowski ◽  
Michael W. McDermott ◽  
...  

Object In 1957, Simpson published a seminal paper defining the risk factors for recurrence following surgical treatment of intracranial meningiomas. Given that Simpson's study was published more than 50 years ago, preceding image guidance technology and MR imaging, the authors reviewed their own experience with surgical treatment of Grade I meningiomas to determine if Simpson's grading scale is still relevant to modern neurosurgical practice. Methods From this cohort, the authors evaluated all patients undergoing craniotomy for resection of a histologically proven WHO Grade I meningioma as their initial therapy. Clinical information was retrospectively reconstructed using patient medical records and radiological data. Recurrence analysis was performed using the Kaplan-Meier method. Results The 5-year recurrence/progression-free survival for all patients receiving a Simpson Grade I, II, III, or IV resection was 95, 85, 88, and 81%, respectively (p = not significant, log-rank test). Kaplan-Meier analysis revealed no significant difference in recurrence-free survival between patients receiving a Simpson Grade I, II, III, or IV resection. Analysis limited to meningiomas arising from the skull base (excluding the cavernous sinus) similarly found no significant benefit to Simpson Grade I or II resection, and the survival curves were nearly superimposed. Conclusions In this study of a cohort of patients undergoing surgery for WHO Grade I meningiomas, the authors demonstrate that the benefit of more aggressive attempts to resect the tumor with dura and underlying bone was negligible compared with simply removing the entire tumor, or even leaving small amounts of tumor attached to critical structures. The authors believe that these data reflect an evolution in the nature of meningioma surgery over the past 2 decades, and bring into question the relevance of using Simpson's grading system as the sole predictor of recurrence.


2004 ◽  
Vol 22 (13) ◽  
pp. 2635-2642 ◽  
Author(s):  
Sabino De Placido ◽  
Giovanni Scambia ◽  
Giovanni Di Vagno ◽  
Emanuele Naglieri ◽  
Alessandra Vernaglia Lombardi ◽  
...  

Purpose Topotecan is an active second-line treatment for advanced ovarian cancer. Its efficacy as consolidation treatment after first-line standard chemotherapy is unknown. Patients and Methods To investigate whether topotecan (1.5 mg/m2 on days 1 through 5, four cycles, every 3 weeks) prolonged progression-free survival (PFS) for patients responding to standard carboplatin (area under the curve 5) and paclitaxel (175 mg/m2 administered as a 3-hour infusion in six cycles; CP), a multicenter phase III study was performed with an 80% power to detect a 50% prolongation of median PFS. Patients were registered at diagnosis and randomized after the end of CP. Results Two hundred seventy-three patients were randomly assigned (topotecan, n = 137; observation, n = 136), with a median age of 56 years. Stage at diagnosis was advanced in three fourths of patients (stage III in 65% of patients; stage IV in 10%); after primary surgery, 46% had no residual disease and 20% were optimally debulked. After CP, 87% reached a clinical complete response, and 13% achieved a partial response. Neutropenia (grade 3/4 in 58% of the patients) and thrombocytopenia (grade 3 in 21%; grade 4 in 3%) were the most frequent toxicities attributed to topotecan. There was no statistically significant difference in PFS between the arms (P = .83; log-rank test): median PFS was 18.2 months in the topotecan arm and 28.4 in the control arm. Hazard ratio of progression for patients receiving topotecan was 1.18 (95% CI, 0.86 to 1.63) after adjustment for residual disease, interval debulking surgery, and response to CP. Conclusion The present analysis indicates that consolidation with topotecan does not improve PFS for patients with advanced ovarian cancer who respond to initial chemotherapy with carboplatin and paclitaxel.


2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 527-527 ◽  
Author(s):  
Annalisa Guida ◽  
Laurence Albiges ◽  
Yohann Loriot ◽  
Christophe Massard ◽  
Karim Fizazi ◽  
...  

527 Background: Currently both E and A are standard treatments for patients (pts) with mRCC after failure of first line therapy (1L)with VEGF-targeted therapy. There is no comparative study reported so far, and this study aims to evaluate these 2 drugs in a large center. Methods: Patient characteristics, safety and outcome data from all mRCC pts who received E or A as 2L at Gustave Roussy from April 2007 to May 2015 have been compared. Progression-free Survival (PFS) and Overall Survival (OS) were assessed by the Kaplan-Meier method and compared with the log-rank test. Results: 81 pts were treated with E and 45 pts with A. The table shows patient characteristics. The 2 groups were similar. The most common 1L was sunitinib (79% in E group and 82.2% in A group). Median follow up was 29 mo (95%CI 26 – 31), 26 mo for A and 33 mo for E (p=0.046). Median OS was 21.5 mo for E and 14.9 mo for A (p = 0.23). Median PFS was 5.3 and 7.7 mo for E and A respectively (p = 0.39). Disease control rate was 69% and 73% (p=0.31) and partial response was achieved in 4% and in 24% of pts (p=0.002), respectively in E and A cohort. At time of analysis E is ongoing in 3 pts (4%) and A in 9 pts (20%) (p=0.008). Third-line therapy (3L) was administrated in 62% of pts after E and in 33% after A (p=0.003). The most common 3L after E is A (48%) and vice versa the most common after A is E (71%). Median PFS of 3L after E is 9.1 mo (12.1 mo for A and 8 mo when 3L is not A (p=0.17)). Median PFS of 3L after A is 7.8 mo (95%CI 4-12). Conclusions: No statistically significant difference for PFS and OS were observed. Nevertheless, A showed more PR than E, while more pts received 3L after E. A remains very active in 3L. [Table: see text]


Blood ◽  
2011 ◽  
Vol 117 (11) ◽  
pp. 3016-3024 ◽  
Author(s):  
Xavier C. Badoux ◽  
Michael J. Keating ◽  
Xuemei Wang ◽  
Susan M. O'Brien ◽  
Alessandra Ferrajoli ◽  
...  

Abstract Optimal management of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) is dictated by patient characteristics, prior therapy, and response to prior therapy. We report the final analysis of combined fludarabine, cyclophosphamide, and rituximab (FCR) for previously treated patients with CLL and identify patients who benefit most from this therapy. We explore efficacy of FCR in patients beyond first relapse, patients with prior exposure to fludarabine and alkylating agent combinations, and patients with prior exposure to rituximab. The FCR regimen was administered to 284 previously treated patients with CLL. Patients were assessed for response and progression by 1996 National Cancer Institute–Working Group (NCI-WG) criteria for CLL and followed for survival. The overall response rate was 74%, with 30% complete remission. The estimated median overall survival was 47 months and median progression-free survival for all patients was 21 months. Subgroup analyses indicated that the following patients were most suitable for FCR treatment: patients with up to 3 prior treatments, fludarabine-sensitive patients irrespective of prior rituximab exposure, and patients without chromosome 17 abnormalities. FCR is an active and well-tolerated therapy for patients with relapsed CLL. The addition of rituximab to FC improved quality and durability of response in this patient population.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii83-ii83
Author(s):  
Nilan Vaghjiani ◽  
Andrew Schwieder ◽  
Sravya Uppalapati ◽  
Zachary Kons ◽  
Elizabeth Kazarian ◽  
...  

Abstract PURPOSE Radiation-induced meningiomas (RIMs) are associated with previous exposure to therapeutic irradiation. RIMs are rare and have not been well characterized relative to spontaneous meningiomas (SMs). METHODS 1003 patients with proven or presumed meningiomas were identified from the VCU brain tumor database. Chart review classified RIM patients and their characteristics. RESULTS Of the 1003 total patients, 76.47% were female with a mean ± SD age of 67.55 ± 15.50 years. 15 RIM patients were identified (66.67% female), with a mean ± SD age of 52.67 ± 15.46 years, 5 were African American and 10 were Caucasian. The incidence of RIMs was 1.49% in our data set. The mean age at diagnosis was 43.27 ± 15.06 years. The mean latency was 356.27 ± 116.96 months. The mean initiating dose was 44.28 ± 14.68 Gy. There was a significant difference between mean latency period and ethnicity, 258.3 months for African American population, and 405.2 months for Caucasian population (p = 0.003). There was a significant difference between the mean number of lesions in females (2.8) versus males (1.2; p = 0.046). Of the RIMs with characterized histology, 6 (55%) were WHO grade II and 5 (45%) were WHO grade I, demonstrating a prevalence of grade II tumors approximately double that found with SMs. RIMs were treated with combinations of observation, surgery, radiation, and medical therapy. Of the 8 patients treated with radiation, 4 demonstrated response. 8 of the 15 patients (53%) demonstrated recurrence/progression despite treatment. CONCLUSION RIMs are important because of the associated higher grade histology, gender, and ethnic incidences, and increased recurrence/progression compared to SMs. Despite the presumed contributory role of prior radiation, RIMs demonstrate a significant rate of responsiveness to radiation treatment.


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