Prophylactic isolated limb perfusion for localized, high-risk limb melanoma: results of a multicenter randomized phase III trial. European Organization for Research and Treatment of Cancer Malignant Melanoma Cooperative Group Protocol 18832, the World Health Organization Melanoma Program Trial 15, and the North American Perfusion Group Southwest Oncology Group-8593.

1998 ◽  
Vol 16 (9) ◽  
pp. 2906-2912 ◽  
Author(s):  
H S Koops ◽  
M Vaglini ◽  
S Suciu ◽  
B B Kroon ◽  
J F Thompson ◽  
...  
Keyword(s):  
Lymph Node ◽  
High Risk ◽  
Regional Lymph Node ◽  
Phase Iii ◽  
World Health ◽  
Isolated Limb Perfusion ◽  
Primary Cutaneous Melanoma ◽  
European Organization ◽  
Limb Perfusion ◽  
The Impact

PURPOSE Patients with primary cutaneous melanoma > or = 1.5 mm in thickness are at high risk of having regional micrometastases at the time of initial surgical treatment. A phase III international study was designed to evaluate whether prophylactic isolated limb perfusion (ILP) could prevent regional recurrence and influence survival. PATIENTS AND METHODS A total of 832 assessable patients from 16 centers entered the study; 412 were randomized to wide excision (WE) only and 420 to WE plus ILP with melphalan and mild hyperthermia. Median age was 50 years, 68% of patients were female, 79% of melanomas were located on a lower limb, and 47% had a thickness > or = 3 mm. RESULTS Median follow-up duration is 6.4 years. There was a trend for a longer disease-free interval (DFI) after ILP. The difference was significant for patients who did not undergo elective lymph node dissection (ELND). The impact of ILP was clearly on the occurrence-as first site of progression - of in-transit metastases (ITM), which were reduced from 6.6% to 3.3%, and of regional lymph node (RLN) metastases, with a reduction from 16.7% to 12.6%. There was no benefit from ILP in terms of time to distant metastasis or survival. Side effects were higher after ILP, but transient in most patients. There were two amputations for limb toxicity after ILP. CONCLUSION Prophylactic ILP with melphalan cannot be recommended as an adjunct to standard surgery in high-risk primary limb melanoma.

20 Prophylactic isolated limb perfusion for high risk (≥ 1.5 mm) limb melanoma phase III trial from EORTC and WHO Melanoma Group

1999 ◽  
Vol 9 (3) ◽  
pp. 316
Author(s):  
F. J. Lejeune ◽  
M. Vaglini ◽  
S. Suciu ◽  
B. B. R. Kroon ◽  
J. F. Thompson ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Iii ◽  
Isolated Limb Perfusion ◽  
Phase Iii Trial ◽  
Limb Perfusion

scholarly journals Longer Follow-Up Confirms Recurrence-Free Survival Benefit of Adjuvant Pembrolizumab in High-Risk Stage III Melanoma: Updated Results From the EORTC 1325-MG/KEYNOTE-054 Trial

2020 ◽  
Vol 38 (33) ◽  
pp. 3925-3936 ◽  
Author(s):  
Alexander M. M. Eggermont ◽  
Christian U. Blank ◽  
Mario Mandala ◽  
Georgina V. Long ◽  
Victoria G. Atkinson ◽  
...  
Keyword(s):  
Lymph Node ◽  
High Risk ◽  
Phase Iii ◽  
Stage Iii ◽  
Recurrence Free Survival ◽  
Meaningful Improvement ◽  
Free Survival ◽  
Stage Iii Melanoma ◽  
The Impact

PURPOSE We conducted the phase III double-blind European Organisation for Research and Treatment of Cancer (EORTC) 1325/KEYNOTE-054 trial to evaluate pembrolizumab versus placebo in patients with resected high-risk stage III melanoma. On the basis of 351 recurrence-free survival (RFS) events at a 1.25-year median follow-up, pembrolizumab prolonged RFS (hazard ratio [HR], 0.57; P < .0001) compared with placebo. This led to the approval of pembrolizumab adjuvant treatment by the European Medicines Agency and US Food and Drug Administration. Here, we report an updated RFS analysis at the 3.05-year median follow-up. PATIENTS AND METHODS A total of 1,019 patients with complete lymph node dissection of American Joint Committee on Cancer Staging Manual (seventh edition; AJCC-7), stage IIIA (at least one lymph node metastasis > 1 mm), IIIB, or IIIC (without in-transit metastasis) cutaneous melanoma were randomly assigned to receive pembrolizumab at a flat dose of 200 mg (n = 514) or placebo (n = 505) every 3 weeks for 1 year or until disease recurrence or unacceptable toxicity. The two coprimary end points were RFS in the overall population and in those with programmed death-ligand 1 (PD-L1)–positive tumors. RESULTS Pembrolizumab (190 RFS events) compared with placebo (283 RFS events) resulted in prolonged RFS in the overall population (3-year RFS rate, 63.7% v 44.1% for pembrolizumab v placebo, respectively; HR, 0.56; 95% CI, 0.47 to 0.68) and in the PD-L1–positive tumor subgroup (HR, 0.57; 99% CI, 0.43 to 0.74). The impact of pembrolizumab on RFS was similar in subgroups, in particular according to AJCC-7 and AJCC-8 staging, and BRAF mutation status (HR, 0.51 [99% CI, 0.36 to 0.73] v 0.66 [99% CI, 0.46 to 0.95] for V600E/K v wild type). CONCLUSION In resected high-risk stage III melanoma, pembrolizumab adjuvant therapy provided a sustained and clinically meaningful improvement in RFS at 3-year median follow-up. This improvement was consistent across subgroups.

scholarly journals Popliteal lymphadenectomy for treating metastatic melanoma: case report

2008 ◽  
Vol 126 (4) ◽  
pp. 232-235 ◽  
Author(s):  
Sergio Renato Pais Costa ◽  
Sergio Henrique Couto Horta ◽  
Alexandre Cruz Henriques
Keyword(s):  
Case Report ◽  
Lymph Node ◽  
Local Excision ◽  
Regional Lymph Node ◽  
Isolated Limb Perfusion ◽  
Necrosis Factor Alpha ◽  
Term Survival ◽  
Regional Lymphadenectomy ◽  
Limb Perfusion ◽  
In Transit

CONTEXT: Regional lymph node involvement in patients with malignant melanomas has been associated with poor prognosis. In-transit metastases also lead to poor long-term survival. Whereas for nodal disease only regional lymphadenectomy offers adequate locoregional control, for in-transit metastasis both local excision and isolated limb perfusion with chemotherapy plus tumor necrosis factor-alpha can be used for disease control. In cases of tumors located in the distal region of the legs, the lymphatic dissemination most commonly observed is to the inguinal chain. Consequently, therapeutic inguinal lymphadenectomy or even selective lymphadenectomy (sentinel lymph node biopsy) have been recommended. On the other hand, involvement of the popliteal chain is very rare. When this occurs, popliteal lymphadenectomy should be indicated. Local excision may be the logical approach for a few small in-transit metastases because of the low morbidity in this procedure, when compared with isolated limb perfusion. CASE REPORT: A case of melanoma of the heel with popliteal chain involvement and in-transit metastases is presented. This was treated by means of regional lymphadenectomy plus in-transit metastases excision, with a good postoperative course.

scholarly journals Regional lymph node infiltration and thick lesions are associated with poor prognosis in high-risk resected melanomas: A retrospective cohort study

2021 ◽  
Vol 61 ◽  
pp. 132-138
Author(s):  
Sumadi Lukman Anwar ◽  
Roby Cahyono ◽  
Heru Yudanto Budiman ◽  
Widya Surya Avanti ◽  
Wirsma Arif Harahap ◽  
...  
Keyword(s):  
Cohort Study ◽  
Lymph Node ◽  
High Risk ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Poor Prognosis ◽  
Regional Lymph Node

Outcome of Treatment with Fludarabine Versus Fludarabine and Cyclophosphamide in Chronic Lymphocytic Leukemia (CLL) Is Adversely Impacted by High Risk Genetic Features: Results from ECOG 2997.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3487-3487 ◽  
Author(s):  
Michael R. Grever ◽  
David M. Lucas ◽  
Gordon W. Dewald ◽  
Donna S. Neuberg ◽  
Ian W. Flinn ◽  
...  
Keyword(s):  
High Risk ◽  
P53 Mutation ◽  
Hazard Ratio ◽  
Phase Iii ◽  
P53 Mutations ◽  
Interphase Cytogenetics ◽  
Molecular Features ◽  
Mutational Status ◽  
Significant Difference ◽  
The Impact

Several prognostic factors including un-mutated VH mutational status, select interphase cytogenetic abnormalities [del(11q22.3), del(17p13.1)] and p53 mutations have been associated with shorter interval time from diagnosis to symptomatic disease requiring treatment, shortened progression-free survival (PFS) and overall survival (OS). Limited prospective data exists relative to the relevance of these biologic markers on PFS following treatment with modern therapies for CLL. E2997 is a randomized phase III trial of 278 previously untreated, symptomatic CLL patients who received fludarabine and cyclophosphamide (FC) versus fludarabine (F). We analyzed the response rates and PFS of the patients for whom interphase cytogenetics, VH mutational status, and p53 mutational status studies have been completed. FC therapy had a higher complete response (CR) (23% versus 5%, p<0.002), overall response [OR] (73% versus 50%, p<0.002), and median PFS (33.5 months versus 15 months, p<.0001) as compared to F. The CR and OR was not different based upon interphase cytogenetics or VH mutational status for the entire group of patients or when analyzed by arm of treatment. However, the OR for pts with del(17) or p53 mutations was lower in both the FC arm (69%, versus 76% in patients with normal p53) and F arm (27%, versus 54% in normal p53). Using the Dohner hierarchical classification [del(17p)>del(11q)>del(6q)>tri12>normal> del(13q14)], the relationship of interphase cytogenetics, VH mutational status and p53 mutational status with PFS is summarized below: Median PFS on FC (months) Median PFS on F (months) NR = median not reached; p53 mut+ = mutation present del(17p) 11.9 8.2 del(11q) 30.6 12.8 del(6q) 26.9 26.7 tri 12 NR 20.3 normal NR 11.2 del(13q) NR 21.2 del(17p)/p53 mut+ 11.9 8.9 no del(17p)/p53 mut+ NR 17.8 VH<98% NR 21.2 VH>98% 21.4 13.4 Using the interphase cytogenetic groups, there was a significant difference in PFS for both the FC (p=0.04) and F (p=0.01) treatment arms. Similarly, the presence of a p53 mutation or deletion [del(17p)] predicted for shorter PFS for both FC (p=0.005) and F (p=0.02) therapies. PFS did not statistically differ among VH mutational groups for either arm. We next investigated a Cox proportional hazards analysis to assess the impact of multiple molecular features and treatment arm on PFS. Treatment with F (hazard ratio 3.14, p<0.0001), presence of del(17p) or p53 mutation (hazard ratio 3.13, p=0.0001), and presence of del(11q) (hazard ratio 2.067, p=0.019) were highly significant in the model. Finally, VH unmutated status and del(11q) were highly associated. In conclusion, our data demonstrate that high risk genomic features including p53 mutations, del(17p), and del(11q) are highly predictive of shortened PFS. Our data provide support for a risk-stratified therapy approach for the treatment of CLL.

Pembrolizumab versus placebo after complete resection of high-risk stage III melanoma: New recurrence-free survival results from the EORTC 1325-MG/Keynote 054 double-blinded phase III trial at three-year median follow-up.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10000-10000 ◽  
Author(s):  
Alexander M. Eggermont ◽  
Christian U. Blank ◽  
Mario Mandalà ◽  
Georgina V. Long ◽  
Victoria Atkinson ◽  
...  
Keyword(s):  
Lymph Node ◽  
High Risk ◽  
Complete Resection ◽  
Phase Iii ◽  
Stage Iii ◽  
Recurrence Free Survival ◽  
Stage Iiia ◽  
Free Survival ◽  
Stage Iii Melanoma

10000 Background: We conducted the phase 3 double-blind EORTC 1325/KEYNOTE-054 trial to evaluate pembrolizumab vs placebo in patients (pts) with resected high-risk stage III melanoma. Based on 351 recurrence-free survival (RFS) events and at a median follow-up of 1.25 years (yrs), pembrolizumab improved RFS (hazard ratio (HR) 0.57, P<0.0001) as compared to placebo (Eggermont, NEJM 2018). This led to the approval of pembrolizumab adjuvant treatment by EMA and FDA. Methods: Eligible pts included those ≥18 yrs of age with complete resection of cutaneous melanoma metastatic to lymph node(s), classified as AJCC-7 stage IIIA (at least one lymph node metastasis >1 mm), IIIB or IIIC (without in-transit metastasis). A total of 1019 pts were randomized (stratification by stage and region) to pembrolizumab at a flat dose of 200 mg (N=514) or placebo (N=505) every 3 weeks for a total of 18 doses (~1 year) or until disease recurrence or unacceptable toxicity. The 2 co-primary endpoints were RFS in the intention-to-treat overall population and in pts with PD-L1-positive tumors. Here, we report an updated RFS analysis based on a longer follow-up. Results: Overall, 15%/46%/39% of pts had stage IIIA/IIIB/IIIC. At 3.05-yr median follow-up, pembrolizumab (190 RFS events) compared with placebo (283 RFS events) prolonged RFS, in the overall population and in the PD-L1 positive tumor subgroup (see Table). RFS was consistently prolonged across subgroups, in particular according to AJCC-7 staging, BRAF-V600 E/K mutation status. Conclusions: Pembrolizumab, administered at 200 mg every 3 weeks for up to 1 year as adjuvant therapy, provided, at a 3-yr median follow-up, a sustained improvement in RFS, which was clinically meaningful, in resected high-risk stage III melanoma. This improvement was consistent across subgroups. In the overall population, the 3-yr cumulative incidence of distant metastasis being the first recurrence was 22.3% (pembrolizumab group) vs 37.3% (placebo group) (HR 0.55, 95% CI 0.44-0.69). Clinical trial information: NCT02362594. [Table: see text]

Accuracy of 68Ga-PSMA-11 for pelvic nodal metastasis detection prior to radical prostatectomy and pelvic lymph node dissection: A multicenter prospective phase III imaging study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5502-5502 ◽  
Author(s):  
Thomas A Hope ◽  
Wesley R Armstrong ◽  
Vishnu Murthy ◽  
Courtney Lawhn Heath ◽  
Spencer Behr ◽  
...  
Keyword(s):  
Lymph Node ◽  
High Risk ◽  
Radical Prostatectomy ◽  
Lymph Node Dissection ◽  
Predictive Value ◽  
False Negative ◽  
Phase Iii ◽  
Nodal Metastases ◽  
Node Dissection ◽  
Node Size

5502 Background: To determine the accuracy of 68Ga-PSMA-11 PET for the detection of pelvic nodal metastases (N1) compared to histopathology at time of radical prostatectomy (RP). Methods: This is a prospective multicenter single-arm open-label phase 3 imaging trial. Patients with intermediate to high risk prostate cancer (PCa) considered for RP with lymph node dissection (PLND) were enrolled at the University of California, Los Angeles (UCLA) and at the San Francisco (UCSF) (NCT03368547, NCT02611882, NCT02919111), and underwent one 68Ga-PSMA-11 PET. The primary endpoint was the sensitivity (Se) and specificity (Sp) of 68Ga-PSMA-11 PET for the N1 detection compared to PLND histopathology (reference-standard) on a per patient basis using nodal region-based correlation. Each scan was read by three blinded independent central readers (BICR). Consensus was based on majority rule. Results: From December 2015 to August 2019, 633 patients underwent one 68Ga-PSMA-11 PET for primary staging, and 277/633 (44%) subsequently underwent RP and PLND. The median initial PSA was 11.1 [0.04-147]. 75/277 patients (27%) had N1 disease per histopathology. Using a regional based analysis, Se, Sp, positive predictive value (PPV) and negative predictive value (NPV) for N1 detection was 0.40 [0.34, 0.46], 0.95 [0.92, 0.97], 0.75 [0.70, 0.80], 0.81 [0.76, 0.85], respectively. Se was higher for patients with higher PSA: 0.29 [0.24, 0.35] for PSA < 11 ng/ml versus 0.48 [0.42, 0.54] for PSA > 11. Se was higher when the nodes were larger: 0.30 [0.25, 0.36] for nodes < 10 mm versus 0.68 [0.63, 0.74] for nodes > 10. The average node size in true positive patients was 10 mm versus 4 mm in false negative patients. Conclusions: In intermediate to high risk PCa patients who underwent RP and PLND, 68Ga-PSMA-11 PET detected pelvic nodal metastases with a sensitivity of 0.40 and a specificity of 0.95. Higher PSAs and larger node size correlated with increased sensitivity. Clinical trial information: NCT03368547, NCT02611882, NCT02919111 .

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