Pathologic Complete Response to Intralesional Interleukin-2 Therapy Associated with Improved Survival in Melanoma Patients with In-Transit Disease

Hassan, Saima; Petrella, Teresa M.; Zhang, Tong; Kamel‐Reid, Suzanne; Nordio, Francesco; Baccarelli, Andrea; Sade, Shachar; Naert, Karen; Habeeb, Ayman Al; Ghazarian, Danny; Wright, Frances C.

doi:10.1245/s10434-014-4199-z

Cited by 16 publications

(25 citation statements)

References 44 publications

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“…Table summarizes the key data for each modality and presents the pooled results including the weighted ORR and meta‐analysis data. Assessed studies included: randomized controlled trials, nonrandomized phase I and II comparative and noncomparative studies, and prospective or retrospective case series (NHMRC levels II–IV evidence; Tables S2‐S9) . Only two therapies: amputation and topical imiquimod, were suitable for formal meta‐analysis ( I 2 value ≤ 40%).…”

Section: Resultsmentioning

confidence: 99%

A systematic review and meta‐analysis of locoregional treatments for in‐transit melanoma

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Lonne

Sparks

et al. 2019

Journal of Surgical Oncology

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Background and Objectives In‐transit melanoma (ITM) metastases present a therapeutic challenge and management decisions can be difficult. There are multiple treatments available, with differing efficacy, and supported by different levels of evidence. The primary objective was to perform a systematic review and where suitable, a meta‐analysis of the literature reporting on the use of locoregional treatments for the management of ITM. Methods An independent review was conducted including a comprehensive search of the National Library of Medicine using PubMed, MEDLINE, Embase, and Cochrane Library databases. Key data were tabulated, synthesized and pooled to calculate relevant weighted effect sizes for each therapy using random‐effect models. The statistical heterogeneity was calculated using the Higgins' method. Results Of the initial 32 612 articles identified, 57 original articles satisfied eligibility criteria. Eight treatment modalities were identified comprising: amputation (7); hyperthermic isolated limb perfusion (15); isolated limb infusion (8); carbon dioxide laser (9); PV‐10 intralesional therapy (5); IL‐2 intralesional therapy (8); imiquimod (7); diphenylcyclopropenone (3). Only amputation and topical imiquimod were suitable for formal meta‐analysis. Conclusions All of the assessed therapies have significant selection bias. Variable levels of evidence support the ongoing use of locoregional treatments and these may significantly improve disease‐free survival.

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Section: Resultsmentioning

confidence: 99%

A systematic review and meta‐analysis of locoregional treatments for in‐transit melanoma

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Lonne

Sparks

et al. 2019

Journal of Surgical Oncology

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“…It represents the largest single institution study to date on IL-2 treatment for in-transit lesions, with almost double the number of patients studied than in previous single institution studies. 5,11 The highest pCR rates were achieved in patients who started on IL-2 (44%) and CLT (58%) and the greatest toxicities were seen amongst patients receiving DPCP (80%) and CLT (67%). However, all toxicities were grade CTCAE grade 1 to 2.…”

Section: Discussionmentioning

confidence: 99%

“…Biopsies of any remaining in transit lesions were performed 8 to 10 weeks after completion of treatment. 5…”

Section: Discussionmentioning

confidence: 99%

“…3,4 Our institution has demonstrated a 32% pCR rate with IL-2. 5 Importantly, having a pCR to IL-2 was associated with improved progression-free survival (HR 0.11; P = .003), and overall survival (P = .004) with a median overall survival not reached after a median follow up of 19.4 months (range 2.0-65.8 months). 5 Topical DPCP has previously resulted in complete clearance of cutaneous in-transit lesions in 46% of patients.…”

Section: Introductionmentioning

confidence: 91%

“…5 Importantly, having a pCR to IL-2 was associated with improved progression-free survival (HR 0.11; P = .003), and overall survival (P = .004) with a median overall survival not reached after a median follow up of 19.4 months (range 2.0-65.8 months). 5 Topical DPCP has previously resulted in complete clearance of cutaneous in-transit lesions in 46% of patients. 6 Our institution has demonstrated a pCR rate of 13%, with a partial response in 27%, and disease stability in 40% amongst 15 consecutive patients treated with DPCP alone.…”

Section: Introductionmentioning

confidence: 91%

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Lesional therapies for in‐transit melanoma

Nadler

Hong

Alavi

et al. 2020

Journal of Surgical Oncology

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Background and Objectives: To describe the outcomes of lesional therapy of in-transit melanoma (ITM) with interleukin-2 (IL-2), diphencyprone (DPCP), combination lesional therapy (IL-2, retinoid, and imiquimod; CLT), and imiquimod. Methods: Data was collected for consecutive patients with ITM receiving lesional therapies from 2008 to 2018 in a retrospective review. Included patients did not have metastatic disease at time of starting on lesional therapy and were not on systemic therapy. The primary outcome was complete pathologic response (pCR). Results: Of 83 patients, 57 (69%) started treatment with IL-2, 10 (12%) with DPCP, 12 (14%) with CLT, and 4 (5%) with imiquimod. pCR was achieved in 34 patients (41%) overall, including 44% starting on IL-2, 20% on DPCP, 58% on CLT, and none on imiquimod (P = .024). With a median follow-up of 45 months, cumulative one-year overall survival was 86%, with the best survival in the CLT group. Forty-eight percent experienced common terminology criteria for adverse events grade 1 or 2 toxicity. A quarter of patients on DPCP discontinued therapy due to toxicity (P = .002). Conclusions: IL-2 may be considered for the treatment of ITM with multiple or rapidly developing lesions where there would otherwise be significant morbidity with surgery, given pCR rates and toxicity.

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Systems Biology and Genomics

Hassan

Heiser

Gray

2017

Holland‐Frei Cancer Medicine

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Overview Cancers are complex, adaptive systems comprised of cancer cells, the proximal and distal cells, and soluble and insoluble proteins that influence the behavior of the cancer cells. Features pertaining to the cancer are referred to as intrinsic to the cancer and those comprising the proximal and distal microenvironments are referred to as extrinsic to the cancer. Genomics studies seek to develop comprehensive cellular and molecular profiles of cancers and cancer systems biology studies seek to develop the experimental and theoretical methods needed to understand how the components work together to determine cancer function. The overall goal of these efforts is to develop the ability to predict the behavior of cancers—including progression and response to therapy—from measurements of the intrinsic and extrinsic molecular and cellular components of the cancers. Here, we review recent progress in international efforts to measure the genomic, epigenomic, and proteomic features (aka omic features) of major tumor types. We summarize work on establishing associations between omic features and cancer behavior. Finally, we summarize the computational and experimental models that are currently being used to understand and manipulate the behavior of complex cancer systems.

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Pathologic Complete Response to Intralesional Interleukin-2 Therapy Associated with Improved Survival in Melanoma Patients with In-Transit Disease

Abstract: Thirty-two percent of patients achieved pCR with intralesional IL-2 therapy and had a significantly improved PFS compared with the rest of the cohort, which may be explained by a systemic CD8+ T-cell response.

Cited by 16 publications

References 44 publications

A systematic review and meta‐analysis of locoregional treatments for in‐transit melanoma

A systematic review and meta‐analysis of locoregional treatments for in‐transit melanoma

Lesional therapies for in‐transit melanoma

Systems Biology and Genomics

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