Surgical removal of the index node marked using magnetic seed localization to assess response to neoadjuvant immunotherapy in patients with stage III melanoma.
Ontology highlight
ABSTRACT:
SUBMITTER: Schermers B
PROVIDER: S-EPMC6593699 | biostudies-literature | 2019 Apr
REPOSITORIES: biostudies-literature
Publications
Surgical removal of the index node marked using magnetic seed localization to assess response to neoadjuvant immunotherapy in patients with stage III melanoma.
Schermers B B Franke V V Rozeman E A EA van de Wiel B A BA Bruining A A Wouters M W MW van Houdt W J WJ Ten Haken B B Muller S H SH Bierman C C Ruers T J M TJM Blank C U CU van Akkooi A C J ACJ
The British journal of surgery 20190318 5
This pilot study explored the value of localized index node removal after neoadjuvant immunotherapy in patients with stage III melanoma, for use as a response indicator to guide the extent of completion lymph node dissection. Promising technology. ...[more]
Similar Datasets
Project description:Immune checkpoint inhibitors (ICI) have drastically changed the landscape of metastatic melanoma management, thus significantly improving survival. Clinically, assessing treatment response may be challenging in a portion of cases due to a massive influx of immune cells into the tumor microenvironment, causing a transient increase in the target lesion size. This phenomenon, coined pseudoprogression, can occur in 5-10% of metastatic patients, and it is commonly followed by a tumor regression. Its incidence, however, may be underestimated, given its ephemeral nature and often being documented in visceral metastatic lesions, which are only assessed by imaging scans every 2-3 months. More recently, ICI has been studied in the neoadjuvant setting, yielding durable pathological responses in patients with cutaneous melanoma. Here, we report a case of a large retroauricular melanoma mass with regional lymph node involvement treated with ipilimumab and nivolumab combination therapy that developed pseudoprogression. Initially documented as an increase in size along with inflammatory features, followed by a dramatic clinical improvement. A complete regression was pathologically documented after 3 months and the patient remains disease-free for 14 months after treatment initiation. In conclusion, we document a pseudoprogression case during neoadjuvant ICI treatment and raise the question of whether the incidence of this phenomenon is higher when observed in superficial lesions, which can be assessed by routine physical exam.
| S-EPMC8255661 | biostudies-literature
Project description:BackgroundNeoadjuvant checkpoint inhibition (CPI) has recently demonstrated impressive outcomes in patients with stage 3 cutaneous melanoma. However, the safety, efficacy, and outcome of neoadjuvant CPI in patients with mucosal melanoma (MM) are not well studied as MM is a rare melanoma subtype. CPI such as combination nivolumab and ipilimumab achieves response rates of 37-43% in unresectable or metastatic MM but there is limited data regarding the efficacy of these agents in the preoperative setting. We hypothesize that neoadjuvant CPI is a safe and feasible approach for patients with resectable MM.MethodUnder an institutionally approved protocol, we identified adult MM patients with resectable disease who received neoadjuvant anti-PD1 +/- anti-CTLA4 between 2015 to 2019 at our institution. Clinical information include age, gender, presence of nodal involvement or satellitosis, functional status, pre-treatment LDH, tumor mutation status, and treatment data was collected. Outcomes include event free survival (EFS), overall survival (OS), objective response rate (ORR), pathologic response rate (PRR), and grade ≥3 toxicities.ResultsWe identified 36 patients. Median age was 62; 58% were female. Seventy-eight percent of patients received anti-PD1 + anti-CTLA4. Node positive disease or satellite lesions was present at the time of treatment initiation in 47% of patients. Primary sites of disease were anorectal (53%), urogenital (25%), head and neck (17%), and esophageal (6%). A minority of patients did not undergo surgery due to complete response (n=3, 8%) and disease progression (n=6, 17%), respectively. With a median follow up of 37.9 months, the median EFS was 9.2 months with 3-year EFS rate of 29%. Median OS had not been reached and 3-year OS rate was 55%. ORR was 47% and PRR was 35%. EFS was significantly higher for patients with objective response and for patients with pathologic response. OS was significantly higher for patients with pathologic response. Grade 3 toxicities were reported in 39% of patients.ConclusionNeoadjuvant CPI for resectable MM is a feasible approach with signs of efficacy and an acceptable safety profile. As there is currently no standard approach for resectable MM, this study supports further investigations using neoadjuvant therapy for these patients.
| S-EPMC9618687 | biostudies-literature
Project description:In this issue of JEM, Reijers et al. (2023. J. Exp. Med.https://doi.org/10.1084/jem.20221952) demonstrate that pre- and post-treatment IFNγ-related gene expression scores are promising markers for choosing neoadjuvant immunotherapy for stage III melanoma.
| S-EPMC10035434 | biostudies-literature
Project description:BackgroundThe frequency of "exhausted" or checkpoint-positive (PD-1+CTLA-4+) cytotoxic lymphocytes (Tex) in the tumor microenvironment is associated with response to anti-PD-1 therapy in metastatic melanoma. The current study determined whether pretreatment Tex cells in locally advanced melanoma predicted response to neoadjuvant anti-PD-1 blockade.MethodsPretreatment tumor samples from 17 patients with locally advanced melanoma underwent flow cytometric analysis of pretreatment Tex and regulatory T cell frequency. Patients who met the criteria for neoadjuvant checkpoint blockade were treated with either PD-1 monotherapy or PD-1/CTLA-4 combination therapy. Best overall response was evaluated by response evaluation criteria in solid tumors version 1.1, with recurrence-free survival (RFS) calculated by the Kaplan-Meier test. The incidence and severity of adverse events were tabulated by clinicians using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.ResultsOf the neoadjuvant treated patients, 10 received anti-PD-1 monotherapy and 7 received anti-CTLA-4/PD-1 combination therapy. Of these 17 patients, 12 achieved a complete response, 4 achieved partial responses, and 1 exhibited stable disease. Surgery was subsequently performed for 11 of the 17 patients, and 8 attained a complete pathologic response. Median RFS and overall survival (OS) were not reached. Immune-related adverse events comprised four grade 3 or 4 events, including pneumonitis, transaminitis, and anaphylaxis.ConclusionThe results showed high rates of objective response, RFS, and OS for patients undergoing immune profile-directed neoadjuvant immunotherapy for locally advanced melanoma. Furthermore, the study showed that treatment stratification based upon Tex frequency can potentially limit the adverse events associated with combination immunotherapy. These data merit further investigation with a larger validation study.
| S-EPMC8317618 | biostudies-literature
Project description:Background:There remains up to a 50% recurrence rate in advanced p16- head and neck squamous cell carcinoma with current standard of care treatment. In an attempt to improve survival, multiple trials administering induction or neoadjuvant chemotherapy have been conducted but none demonstrated improved overall survival. The established efficacy of immune checkpoint inhibitors in the recurrent and metastatic setting has produced widespread interest in their neoadjuvant use. Purpose:To survey the landscape of active neoadjuvant immunotherapy trials in head and neck squamous cell carcinoma and summarize and synthesize currently available outcomes from these trials. Conclusions:Neoadjuvant immunotherapy has proven safe and well tolerated in head and neck squamous cell carcinoma with encouraging efficacy results, including relatively high rates of pathologic response. Ongoing studies offer an opportunity to study immune responses in vivo. PD-L1 positivity, high tumor mutational burden and infiltration of NK cells, CD8, CD26 and Tim3 positive lymphocytes at time of surgery have been correlated with pathologic responses. We await updated reports of disease free survival and overall survival data and results of ongoing phase III studies utilizing neoadjuvant immunotherapy to determine if this treatment paradigm will have a place in the standard of care treatment in head and neck squamous cell carcinoma.
| S-EPMC7077151 | biostudies-literature
Project description:Neoadjuvant immunotherapy may improve outcomes in patients with resectable NSCLC and is being evaluated in phase 2 and 3 studies. Nevertheless, preoperative treatment postpones resection; the potential for increased surgical complexity and greater intra- and postoperative morbidity and mortality is an additional consideration. In studies primarily designed to evaluate efficacy, the impact of neoadjuvant immunotherapy on surgery is based on parameters that are poorly defined and reported differently between studies. Defining and reporting common end points among trials would improve understanding and facilitate cross-comparison of different immunotherapy regimens and may facilitate wider adoption of induction therapies by surgeons and oncologists. We propose several surgical end points and related metrics for neoadjuvant immunotherapy in resectable NSCLC. These include the periods from screening to treatment initiation and from last neoadjuvant dose to surgery; reporting of the allowable window for surgery to preclude masking delays caused by induction treatment-related toxicity; complete resection (R0) rate; preoperative downstaging; a standardized list of immune-related adverse events and associated delay to surgery; preoperative attrition; postoperative attrition before adjuvant therapy; and postoperative 30- and 90-day mortality and morbidity rates. Intraoperative end points (blood loss, duration, and type of surgery) and our proposed system of grading complexity based on lymphadenopathy and fibrosis would allow quantitation of technical difficulty and quality of oncologic resection. In conclusion, the standardization, reporting, and prospective inclusion of these end points in study protocols would provide a comparative overview of the impact of different neoadjuvant immunotherapy regimens on surgery and ultimately clinical oncologic outcomes in resectable NSCLC.
| S-EPMC8552106 | biostudies-literature
Project description:Melanoma is the third most common skin cancer but the leading cause of death from cutaneous malignancies. Although early-stage disease is frequently cured by surgical resection with excellent long-term survival, patients with deeper primary lesions (AJCC stage IIB-C) and those with microscopic (IIIA) or clinically evident regional lymph node or in-transit metastases (IIIB-C) have an increased risk of relapse and death, the latter approaching 70% or more at 5 years. In patients at high risk of recurrence/metastases, adjuvant therapy with high-dose interferon alpha-2b (HDI) following definitive surgical resection has been shown to improve relapse-free and overall survival. Neoadjuvant chemotherapy and/or radiotherapy have offered the prospect to improve regional recurrence risk and overall survival in several solid tumors. The advent of effective new molecularly targeted therapies for metastatic disease and new immunotherapies that overcome checkpoints of immune response have augmented the range of new options that are in current trial evaluation to determine their role as potential adjuvant therapies, alone and in combination with one another, and the established modality of IFN-α. The differential characteristics of the host immune response between early and advanced melanoma provide a strong mechanistic rationale for the use of neoadjuvant immunotherapeutic approaches in melanoma, and the opportunity to evaluate the mechanism of action suggest neoadjuvant trial evaluation for each of the new candidate agents and combinations of interest. Several neoadjuvant trials have been conducted in the phase II setting, which have illuminated the mechanism of IFN-α, as well as providing insight to the effects of anti-CTLA4 blocking antibodies. These agents (anti-CTLA4 blocking antibody ipilimumab, and BRAF inhibitor vemurafenib) are likely to be followed by other immunotherapies that may overcome the PD-1 checkpoint (anti-PD1 and anti-PDL-1) as well as other molecularly targeted agents such as the BRAF inhibitor dabrafenib and the MEK inhibitors trametinib, selumetinib, and MEK162 in the near future. Evaluation of the clinical role of these agents as adjuvant therapy will take years to accomplish to ascertain the relapse-free survival benefits and overall survival benefits of these agents, but neoadjuvant exploration may provide early critical evidence of the therapeutic benefits, as well as clarifying the mechanisms of these agents alone and in combination.
| S-EPMC3654101 | biostudies-literature
Project description:BackgroundNeoantigens are considered ideal targets for immunotherapy, especially tumor vaccine, because of their strong specificity and immunogenicity. Here, we developed a neoantigen nanovaccine used liposomes with lymph-node targeting characteristic.MethodsOur nanovaccine was composed of neoantigens, an amphiphilic liposome and an adjuvant Montanide™ ISA 51. Small animal imaging system and immunofluorescence staining were used to identify the distribution of nanovaccines. A subcutaneous-tumor-resection mouse model of melanoma was established to evaluate the anti-tumor efficacy. Flow cytometry was performed to assay the immune responses initiated by nanovaccines.ResultsNanovaccines could traffic to lymph nodes, be uptaken by CD11c+ DCs and promote DCs maturity. After the treatment of our neoantigen nanovaccines, the average recurrence time was extended from 11 to 16 days and the median survival time was even prolonged 7.5 days relative to the control group (NS group). Nanovaccines increased neoantigen-specific T cells to 10-fold of free vaccines, and upregulated Th1 cytokines, such as IFN-γ and TNF-α. The anti-tumor activity of spleen lymphocytes in the nanovaccine group was significantly stronger than that of other groups. However, some immune-inhibitory cells or molecules in tumor microenvironment have been detected upregulated under the immune pressure of neoantigen nanovaccines, such as Tregs and PD-L1. The efficacy of the neoantigen nanovaccine combined with anti-PD1 antibody or Treg inhibiting peptide P60 was better than that of the single treatment.ConclusionsWe developed a general vaccine strategy, triggering specific T cell responses, and provided feasible combination strategies for better anti-tumor efficacy.
| S-EPMC9006542 | biostudies-literature
Project description:BackgroundNeoadjuvant therapy improves recurrence-free survival (RFS) in resectable stage III cutaneous melanoma. However, accurately predicting individual recurrence risk remains a significant challenge. We investigated circulating tumour DNA (ctDNA) as a biomarker for recurrence in measurable stage IIIB/C melanoma patients undergoing neoadjuvant immunotherapy.MethodsPlasma samples were collected pre-neoadjuvant treatment, pre-surgery and/or six weeks post-surgery from 40 patients enrolled in the OpACIN-neo and PRADO clinical trials. Patients received two cycles of ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) before surgery. Cell free DNA (cfDNA) underwent unbiased pre-amplification followed by tumour-informed mutation detection using droplet digital polymerase chain reaction (ddPCR) with the Bio-Rad QX600 PCR system.ResultsPre-treatment ctDNA was detectable in 19/40 (48%) patients. Among these, 17/19 (89%) zero-converted within six weeks of surgery and none recurred. Positive ctDNA post-surgery (N = 4), irrespective of pre-treatment ctDNA status, was 100% predictive of recurrence (sensitivity 44%, specificity 100%). Furthermore, ctDNA cleared prior to surgery in 7/9 (78%) patients who did not recur, warranting further investigation into ctDNA-guided surgical management.ConclusionPost-surgery ctDNA positivity and zero-conversion are highly predictive of recurrence, offering a window for personalised modification of adjuvant therapy.
| S-EPMC11337884 | biostudies-literature
Project description:Melanoma is the deadliest form of skin cancer and one of the few malignancies whose incidence is on the rise. The treatment of metastatic melanoma continues to be quite challenging, although in recent years, there has been significant progress. Current National Comprehensive Cancer Network guidelines list immunotherapy, chemotherapy, surgery and clinical trials as potential options for patients with metastatic disease but do not clearly recommend which is superior. Additionally, when utilizing combined modality treatment there are no clear guidelines for the optimal timing of surgery in the treatment of metastatic melanoma. In this paper we sought to compile the current evidence and on-going trials in order to provide a comprehensive review of the different options available and underway in regards to the treatment of metastatic melanoma. It is clear that with the responses now seen with systemic immunotherapies and targeted therapies, an expanded role for surgery is the logical next step.
| S-EPMC6094597 | biostudies-literature