Adrenalectomy for Metastatic Melanoma: Current Role in the Age of Nonsurgical Treatments

2015 ◽  
Vol 81 (10) ◽  
pp. 1005-1009 ◽  
Author(s):  
Devin C. Flaherty ◽  
Gary B. Deutsch ◽  
Daniel D. Kirchoff ◽  
Jihey Lee ◽  
Kelly T. Huynh ◽  
...  
Keyword(s):  
Overall Survival ◽  
Metastatic Melanoma ◽  
Surgical Resection ◽  
Stage Iv ◽  
Nonoperative Treatment ◽  
Unknown Primary ◽  
Adrenal Metastases ◽  
Term Survival ◽  
Relative Value ◽  
Resection Of Metastases

Surgical resection of metastases to the adrenal gland can improve overall survival of patients with stage IV melanoma, but its relative value with respect to current nonsurgical therapies is unknown. We hypothesized that surgery remains an optimal first-line treatment approach for resectable adrenal metastases. A search of our institution's prospectively collected melanoma database identified stage IV patients treated for adrenal metastases between January 1, 2000, and August 11, 2014. The 91 study patients had a mean age of 60.3 years at diagnosis of adrenal metastasis and 24 had undergone adrenalectomy. Improved survival was associated with an unknown primary lesion, surgical resection, and nonsurgical therapies. Median overall survival from diagnosis of adrenal metastases was 29.2 months with adrenalectomy versus 9.4 months with nonoperative treatment. Adrenalectomy, either as complete metastasectomy or targeted to lesions resistant to systemic therapy, is associated with improved long-term survival in metastatic melanoma.

Immunotherapy disparities in metastatic melanoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9525-9525 ◽  
Author(s):  
Thomas Oliver ◽  
Todd A. Pezzi ◽  
Ashley E. Pezzi ◽  
Amanda Shreders ◽  
Henry Dao ◽  
...  
Keyword(s):  
Overall Survival ◽  
Metastatic Melanoma ◽  
Median Overall Survival ◽  
Stage Iv ◽  
Therapy Response ◽  
Subsequent Development ◽  
The United States ◽  
Community Practice ◽  
Term Survival ◽  
Dismal Prognosis

9525 Background: Historically, patients with advanced malignant melanoma had a dismal prognosis with an estimated median overall survival of nine months. Therapy response rates and long-term survival have significantly improved with the advent of immunotherapies and targeted chemotherapies. First approved in 2011, there has been subsequent development of more advanced immunotherapeutic agents and targeted chemotherapies, with continued improvement in median overall survival. We examined patterns in the use of immunotherapy and other systemic therapies for metastatic melanoma, as well as the demographic and socioeconomic predictors for the use of these therapies, in order to identify and understand potential barriers to access in the United States. Methods: We used the NCDB for all patients aged 18-years and older who were diagnosed with metastatic melanoma of cutaneous origin from 2004-2014. Patients were included if they had distant metastases or American Joint Committee on Cancer (AJCC) Stage IV. Sociodemographic data, including race, age, insurance status, facility providing care, Charlson/Deyo comorbidity score11, and education by patient’s zip code, were collected. Results: In patients under age 65 with a Charlson-Deyo score of zero, immunotherapy utilization ranged between 8.5–13.4% during 2004 to 2010. In 2011, the usage increased to 16.5% and rose every subsequent year to 29.6% in 2014. Patients were less likely to receive immunotherapy if they had no insurance, were of older age, or received care at a community practice rather than an academic center. Those who received immunotherapy had greater overall survival compared with those who did not. Conclusions: Immunotherapy and targeted agents have become standard of care in those with metastatic melanoma. Adoption of immunotherapy use for metastatic melanoma has been relatively slow despite evidence showing an overall survival benefit; our analysis suggests this is explained in part by socioeconomic barriers.

Prognostic factors in metastatic melanoma patients treated with biochemotherapy and maintenance immunotherapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9051-9051
Author(s):  
D. R. Minor ◽  
M. Kashani-Sabet ◽  
D. Moore ◽  
C. Kim ◽  
S. S. Venna ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Metastatic Melanoma ◽  
Median Survival ◽  
Performance Status ◽  
Intensive Therapy ◽  
Stage Iv ◽  
Treatment Center ◽  
Term Survival ◽  
Melanoma Patients

9051 Background: Patients with stage IV metastatic melanoma are usually felt to be incurable with a median survival of 6.4 months and a 5-year survival of only 2%. Biochemotherapy has shown promise with long-term survival in selected patients. We felt the study of prognostic factors would determine which patients might benefit the most from this intensive therapy. Methods: 135 consecutive patients with stage IV melanoma treated with decrescendo biochemotherapy followed by maintenance immunotherapy at one melanoma treatment center were studied to determine the most important prognostic factors; these factors were then validated by analysis of 133 patients treated in a multi-center trial at other institutions. Patients were treated using the inpatient regimen of O'Day (JCO23:710s,2005 abstract). Results: Median overall survival (OS) was 16.6 months with 1-year survival of 70% and 5-year survival of 28%. Median progression-free survival (PFS) was 7.6 months with 15% progression-free at 5 years. PFS curves showed no relapses after 30 months, so remissions were durable. For OS performance status 0, normal LDH, stage M1a, and non-visceral sites of metastases were favorable prognostic factors. For PFS performance status 0, normal LDH, female sex, age <50 and stage M1a were favorable prognostic factors Multivariate analysis demonstrated two important prognostic factors for survival: normal serum LDH and the presence of either skin or nodes as one of the sites of metastatic disease. The group with normal LDH and skin or node metastases had a relatively good prognosis with median survival of 44 months and a 5-year survival of 38%. Conversely patients with elevated LDH without any skin or nodal metastases had a poor prognosis, with no long-term survivors. Conclusions: Metastatic melanoma patients treated with biochemotherapy and maintenance immunotherapy that have either a normal LDH or skin or nodes as one of their metastatic sites may have durable remissions of their disease, and this therapy should be studied further in these groups. [Table: see text]

Myeloid-derived suppressor cell quantity prior to treatment with ipilimumab at 10mg/kg to predict for overall survival in patients with metastatic melanoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2518-2518 ◽  
Author(s):  
Shigehisa Kitano ◽  
Michael Andrew Postow ◽  
Czrina Cortez ◽  
Teresa Rasalan ◽  
Humilidad F. Gallardo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Overall Survival ◽  
T Cell ◽  
Metastatic Melanoma ◽  
Peripheral Blood ◽  
Clinical Benefit ◽  
Stage Iv ◽  
T Cell Proliferation ◽  
Pre Treatment

2518 Background: Ipilimumab, an antibody that blocks the function of the immune inhibitory molecule cytotoxic T lymphocyte antigen 4 (CTLA-4), significantly prolongs survival in patients with metastatic melanoma. Approximately 30% of patients derive clinical benefit from therapy. Defining biomarkers of response to ipilimumab therapy would enable selection of patients more likely to respond and is relevant for both practicing clinicians and for clinical trial design. We performed a pilot correlative study evaluating myeloid derived suppressor cells (MDSC), a population of immune suppressive monocytic cells, as a biomarker of clinical outcome. Methods: Peripheral blood from 26 patients with stage IV melanoma treated with ipilimumab 10mg/kg every 3 weeks for 4 doses at our center, as part of an expanded access program (BMS CA184-045) was assessed for MDSC quantity (%CD14+,HLA-DRlow/- cells) pre-treatment, at week 7, week 12, and week 24 by flow cytometry. MDSC ability to inhibit T cell proliferation was tested using an in vitro suppression assay. Results: We found that lower MDSC quantity pre-treatment predicted for improved overall survival (Hazard ratio 1.07 (1.03, 1.11) p=0.002) and trended toward associating with clinical benefit measured at week 24 imaging (p=0.09). This effect was independent of pre-treatment or week 7 absolute lymphocyte counts (ALC) and pre-treatment LDH when evaluated in a multivariate model with ALC and MDSC quantity HR 1.10; 95% CI 1.04, 1.17 p=0.0006 and LDH and MDSC quantity HR 1.06; 95% CI 1.01, 1.11 p = 0.013. Furthermore, a general trend of increasing MDSC number by week 24 from the pre-treatment baseline was associated with patients that did not achieve clinical benefit. MDSC suppressed peripheral blood T cell proliferation as measured by CFSE dilution in response to anti-CD3 antibody stimulation. Conclusions: Pre-treatment MDSC quantity may predict clinical response following ipilimumab therapy. Further studies evaluating MDSC as a biomarker of ipilimumab therapy are warranted both retrospectively and prospectively in a broader group of patients.

Impact of care at Memorial Sloan Kettering Cancer Center (MSKCC): A comprehensive cancer center on overall survival (OS) in patients (pts) with AJCC stage IV pancreas adenocarcinoma (PDAC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18128-e18128
Author(s):  
Fiona Boland ◽  
Ahmad Cheema ◽  
Maeve Aine Lowery ◽  
Kenneth H. Yu ◽  
Anna M. Varghese ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Rates ◽  
Stage Iv ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Contributing Factors ◽  
Term Survival ◽  
Entire Cohort ◽  
Line Therapy ◽  
Centralized Care

e18128 Background: PDAC has a rising incidence and relatively static mortality rates. Current cytotoxic regimens confer median survivals of 8.5- 11 months (Von Hoff, Conroy, et al. NEJM 2013, 2011). National Cancer Institute-designated Comprehensive Cancer Centers potentially allow greater access to multidisciplinary consultation for complex cancer care. Although the widespread benefits of NCICCCs are acknowledged, there is limited data demonstrating superior outcomes for patients treated at these centers. Methods: Patients with stage IV PDAC, diagnosed between 01/01/13 and 12/31/14, were identified and followed until death or 12/31/2016. These patients had care centralized to MSKCC and the analysis was conducted to evaluate key patient (pt) and disease characteristics, systemic therapies and outcomes.Survival times were calculated from the date of diagnosis. Results: N=391 pts identified, 210 males (54%), 181 females (46%). Median age 66 years (range 27-91). Table 1 outlines key points. For entire cohort, median overall survival (mOS): 11.4 + 9 months, 1-year (yr) and 2-yr survival rates (SR) of 48% and 15.1% respectively. N= 165 (42%) received mFOLFIRINOX-based regimen as 1st-line therapy with mOS 13.2 + 8.9 months, 1-yr and 2-yr SR of 59.4.% and 20% respectively. N= 118 (30.1%) received gemcitabine + nab-paclitaxel- based regimen as 1st line therapy had a mOS of 11.6 + 9 months with 1-yr and 2-yr SR of 49.1% and 16.2% respectively. Conclusions: At MSKCC, a major referral center for PDAC, outcomes for stage IV disease compare favorably to contemporary trial outcomes with notable 2-yr survivorship (long-term survival analysis of MPACT trial showed 1-yr and 2-yr SR of 35% and 10% respectively). Contributing factors likely reflect multidisciplinary expertize, patient selection and biases. Centralized care for complex illnesses may improve outcomes. [Table: see text]

Progression-free and overall survival analysis in patients with metastatic melanoma undergoing first- versus second-line therapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9078-9078
Author(s):  
J. B. Allred ◽  
V. Suman
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Metastatic Melanoma ◽  
Clinical Outcomes ◽  
Proportional Hazards ◽  
Stage Iv ◽  
Cox Proportional Hazards ◽  
Line Therapy ◽  
The Relationship ◽  
Stage Iv Melanoma

9078 Background: A frequently discussed topic at meetings of oncologists is the question of expected clinical outcomes for patients with metastatic melanoma undergoing 1st vs 2nd line systemic therapy. Differing outcomes in these two patient populations could affect interpretation of non-randomized clinical trials involving both patient populations. Some have suggested superior clinical outcome in patients undergoing 2nd line therapy. As there is little data addressing this issue, we sought to answer the question by comparing the clinical outcomes of patients with metastatic melanoma treated on 1st vs 2nd line therapy across clinical trials conducted at our institution. Methods: Data were collected from 10 phase II clinical trials for patients with stage IV melanoma for which Mayo Clinic was the data center. The 10 trials included three categories of treatments: cytotoxic chemotherapy (4), cancer vaccines (4), and biologic agents (2). In all studies, eligibility criteria required: stage IV melanoma, life expectancy >3 months, reasonable hematology and serum chemistry laboratory results, and an ECOG performance status of ≤2. Cox proportional hazards models were fit to assess the relationship between patients' “therapy” status (1st vs 2nd line) and time to events, both overall survival (OS) and progression free survival (PFS), for each treatment category. Results: We identified 318 unique eligible patients across 10 trials. Removed from the analysis were 55 patients (ocular melanoma and/or metastases involving the central nervous system) leaving 263. Cox proportional hazards results demonstrated no differences in PFS or OS for 1st vs 2nd line patients for either “chemotherapy” or “vaccine” treatment regimens. However, patient treated on “biologic” trials as 1st line therapy appeared to demonstrate a PFS advantage over 2nd line treatments (HR=1.98, p-value=0.02). There was a suggestion of an OS benefit for 1st line patients in this category, however, the relationship was not significant (HR=1.77, p=0.07). Conclusions: The presented data suggest that there is no PFS/OS difference in stage IV melanoma patients receiving 1st vs 2nd line therapy (no PFS/OS advantage to patients treated in 2nd line vs. 1st line). No significant financial relationships to disclose.

Immunological and biological changes during ipilimumab (Ipi) treatment and their correlation with clinical response and survival.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8573-8573 ◽  
Author(s):  
Ester Simeone ◽  
Giusy Gentilcore ◽  
Anna Romano ◽  
Antonio Daponte ◽  
Corrado Caraco ◽  
...  
Keyword(s):  
Overall Survival ◽  
Metastatic Melanoma ◽  
Clinical Parameter ◽  
Phase Iii ◽  
Response To Treatment ◽  
Rank Test ◽  
P Value ◽  
Term Survival ◽  
Overall Survival Benefit ◽  
The Moment

8573 Background: Ipilimumab (Ipi) is approved in the US as first and second line therapy in patients with metastatic melanoma (MM) and in MM patients with previous therapy in the EU, based on an overall survival benefit shown in a phase III study (Hodi, NEJM 2010). To date, no clinical parameter has been found to be predictive for response to treatment and only few immunologic changes have been identified as potential candidates. Methods: From June 2010 to November 2011 we treated in the Expanded Access Program with Ipi at 3 mg/kg, 95 pre-treated metastatic melanoma patients. The median age was 58 yrs (range 17-84); 10 pts (10,5%) were stage IIIc inoperable, 2 pts (2,1%) stage M1a, 4 pts (4,2%) stage M1b, and 79 pts (83,2%) stage M1c. 30/95 pts had brain metastases and 1/95 spinal cord metastases. All 95 patients were evaluable for response (DCR = CR+PR+SD according the irRC), overall survival, safety, including changes in LDH, CRP (C-reactive protein) and lymphocyte populations (CD4+,CD4CD25+,FOXP3/T-Reg cells). PBMC and sera were collected at week 0, 4, 7, 10 and 12. Results: We found a statistical significant decrease of LDH, CRP and FOXP3/T-Reg cells (p<0.0001; χ2 and Mann-Whitney), and an increase of lymphocyte count (p<.0001) in the responders group. These differences were also correlated to survival (log-rank test). No differences were observed for CD4+ and CD4+CD25+ between responders and non-responders (p=0.39;p=0.83; Mann-Whitney). An ORR of 22.1% (1CR+20PR; 95% CI 13.8-30.4) and a DCR at week 24 of 37.9% (36/95; 28.1-47.6, 95% CI) were observed. Median overall survival was estimated of 7.8 months (95%CI:5.0-10.6), with a p value not evaluable at the moment of the analysis due to insufficient follow-up because of long-term survival. Adverse events were registered in 40% (38/95) of patients and the most frequent were of grade 1 and 2 (pruritus 57.9%; rash 5.3%; thyroditis 5.3%). Conclusions: The decrease of LDH, CRP and T-Reg cells during Ipi treatment suggest these parameters should be further explored as potential predictive markers for response and survival. Given the potential clinical utility of these findings, these data warrants further prospective validation in a randomized trial.

Sequential treatment with ipilimumab and BRAF inhibitors in patients with metastatic melanoma: Data from the Italian cohort of ipilimumab expanded access programme (EAP).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9035-9035 ◽  
Author(s):  
Paolo Antonio Ascierto ◽  
Ester Simeone ◽  
Vanna Chiarion-Sileni ◽  
Paola Queirolo ◽  
Michele Del Vecchio ◽  
...  
Keyword(s):  
Overall Survival ◽  
Metastatic Melanoma ◽  
Disease Progression ◽  
Median Overall Survival ◽  
Therapeutic Option ◽  
Braf Inhibitor ◽  
Stage Iv ◽  
Sequential Treatment ◽  
Braf Inhibitors ◽  
A Prospective Study

9035 Background: Ipilimumab and vemurafenib have recently been approved as single agents for the treatment of unresectable or metastatic melanoma. Currently, limited data exist on the sequential treatment with these agents in patients (pts) with the BRAF mutation; here we evaluate the efficacy outcomes of pts enrolled in the EAP in Italy who sequentially received a BRAF-inhibitor and ipilimumab, or vice versa. Methods: Ipilimumab was available upon physician request for pts aged ≥16 years with unresectable stage III/stage IV melanoma who had either failed systemic therapy or were intolerant to ≥1 systemic treatment and for whom no other therapeutic option was available. Ipilimumab 3 mg/kg was administered intravenously every 3 weeks for 4 doses. Tumour assessments were conducted at baseline and after completion of induction therapy using immune-related response criteria. Patients were considered for this analysis if they tested positive for the BRAF mutation and had received a BRAF-inhibitor before or after ipilimumab treatment. Results: In total, 855 Italian pts participated in the EAP from June 2010 to January 2012 across 55 centres. Out of 173 BRAF positive pts, 93 (53.7%) were treated sequentially with both treatments: 48 pts received a BRAF inhibitor upon disease progression with ipilimumab and 45 pts received ipilimumab upon disease progression with a BRAF inhibitor. As of December 2012, median overall survival was 14.5 months (11.1-17.9) and 9.7 months (4.6-14.9) for the two groups, respectively (p=0.01). Among the 45 BRAF inhibitors pretreated pts, 18 (40%) had rapid disease progression (median overall survival: 5.8 months) and were unable to complete all four induction doses of ipilimumab, while the remaining 27 (60%) pts had slower disease progression (median overall survival: 19.3 months) and were able to complete the therapy with ipilimumab. Conclusions: These preliminary results suggest that, in BRAF-mutated pts, to start the sequential treatment with ipilimumab can provide a better survival than the reverse sequence. These findings deserve confirmation in a prospective study.

Does up-front definitive surgical resection with delayed chemotherapy in patients with stage IV rectal cancer compromise overall survival?

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 586-586
Author(s):  
Bindu V. Manyam ◽  
Shlomo A. Koyfman ◽  
Davendra Sohal ◽  
Ismail Mallick ◽  
Chandana A. Reddy ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Overall Survival ◽  
Surgical Resection ◽  
Proportional Hazards ◽  
Performance Status ◽  
Rectal Adenocarcinoma ◽  
Stage Iv ◽  
Cox Proportional Hazards ◽  
Significant Difference ◽  
Poorly Differentiated

586 Background: Definitive resection of the primary is frequently part of the management of patients (pts) with stage IV rectal cancer with good performance status and low volume of systemic metastases. It is unclear whether delaying systemic therapy for up front surgical management of the primary compromises overall survival (OS). Methods: Pts with metastatic rectal adenocarcinoma who received definitive surgical resection between 1998-2011 were identified in an IRB approved registry. The sequencing of CT and surgery, and the use of perioperative radiation therapy (RT), was at the discretion of treating physicians. Preoperative chemotherapy (Pre-CT) regimens included 5-fluorouracil (5-FU) +/- leukovorin (LV), capecitabine, 5-FU/LV/oxaliplatin +/- avastin, or 5-FU/LV/irinocetan. RT dose was typically 50.4 Gy. OS was measured from the date of diagnosis. Baseline variables were compared using the Chi-square and unpaired t-tests. OS was calculated using the Kaplan Meier method. Univariate (UVA) and multivariate analysis (MVA) were performed using Cox proportional hazards regression to identify variables associated with OS. Results: In this study of 115 pts, 75 (65%) were treated with pre-CT, while 40 (35%) were treated with up front surgery. Of the pts who received surgery up front, 3 (8%) received RT and of the pts who received pre-CT, 62 (83%) received RT. The cohort was predominantly male (70%) with a median age of 57, median KPS of 80, and median follow-up of 24.1 months. 94% of pts had T3/T4 tumors, 80% had N+ disease, and 33% had poorly differentiated tumors. Liver directed therapy (LDT) was performed in 61% of pts. There was no significant difference in OS (32.3 vs. 32 months; p = 0.24) between pts treated with pre-CT and those who received surgery up front, respectively. UVA demonstrated that pre-CT was not associated with OS (HR 1.26; p = 0.544). MVA demonstrated that pts with poorly differentiated tumors (HR 2.04; p = 0.007) and those that did not undergo LDT (HR 2.45; p = 0.001) had inferior survival. Conclusions: Delaying systemic chemotherapy in order to achieve local control with surgical resection up front does not appear to impact OS in pts with stage IV rectal cancer.

Does Surgical Resection Have a Role in the Treatment of Large or Multinodular Hepatocellular Carcinoma?

2010 ◽  
Vol 76 (11) ◽  
pp. 1189-1197 ◽  
Author(s):  
Giovanni Ramacciato ◽  
Paolo Mercantini ◽  
Niccolò Petrucciani ◽  
Matteo Ravaioli ◽  
Alessandro Cucchetti ◽  
...  
Keyword(s):  
Overall Survival ◽  
Liver Resection ◽  
Surgical Resection ◽  
Survival Rates ◽  
Treatment Modalities ◽  
Impaired Liver Function ◽  
Term Survival ◽  
Impaired Liver ◽  
Disease Free

Several effective treatments are available for patients with small solitary hepatocellular carcinomas (HCCs). Conversely, the management of patients with large or multinodular HCCs is controversial, and the role of surgical resection is not well defined. Between 2000 and 2006, 51 patients with large or multinodular HCC underwent liver resection. Clinicopathologic and follow-up data were prospectively collected and retrospectively reviewed. The perioperative and long-term outcomes were analyzed. Univariate and multivariate analysis of prognostic factors were conducted. Although 20 patients had multinodular HCCs, 31 had large solitary tumors. Perioperative mortality occurred in eight patients and complications in 15. In patients with large solitary tumors, 5-year disease-free and overall survival were 41.3 per cent and 56.1 per cent, respectively. Those with multinodular HCCs demonstrated 5-year disease-free and overall survival rates of 0 per cent and 33.6 per cent, respectively. Liver resection can result in long-term survival in select patients with large or multinodular HCCs, even in select patients with impaired liver function. Large solitary HCCs seem to have better prognoses than multinodular tumors, with lower recurrence and higher survival rates after surgery. Randomized controlled trials comparing resection to other treatment modalities are indicated to determine optimal patient management.

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