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Pulmonary metastasectomy in the era of targeted therapy and immunotherapy.

ABSTRACT: Metastatic melanoma is a fatal malignancy with a high mortality and morbidity. Since the early 1970s, available medical therapies were limited in improving survival. Surgery represented the best chance for a cure. However, surgery could only be offered to selected patients. The current landscape of treatment has radically evolved since the introduction of targeted and immunotherapies including BRAF and MEK inhibitors, and checkpoint blockers, like PD-1 and CTLA-4 antibodies. These new therapies have seen survival rates matching, and in some cases surpassing, that of surgery. Anti-PD1 and CTLA-4 combination treatments are associated with severe side effects and BRAF and MEK inhibitor combinations may trigger initial tumour responses but prolonged use have resulted in the development of resistant tumour clones and disease relapse. This review examines the role of pulmonary metastasectomy for lung metastasis from malignant melanoma in the current landscape of effective targeted therapy and immunotherapy.

SUBMITTER: Bong CY

PROVIDER: S-EPMC8107521 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Pulmonary metastasectomy in the era of targeted therapy and immunotherapy.

Bong Christopher Y CY Smithers B Mark BM Chua Terence C TC

Journal of thoracic disease 20210401 4

Metastatic melanoma is a fatal malignancy with a high mortality and morbidity. Since the early 1970s, available medical therapies were limited in improving survival. Surgery represented the best chance for a cure. However, surgery could only be offered to selected patients. The current landscape of treatment has radically evolved since the introduction of targeted and immunotherapies including BRAF and MEK inhibitors, and checkpoint blockers, like PD-1 and CTLA-4 antibodies. These new therapies ...[more]

PMID: 34012610

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Contemporary trends in utilization of metastasectomy in the era of targeted and immunotherapies.

Project description:BackgroundMetastasectomy is a useful adjunct in the management of metastatic cancer. Widespread adoption of novel targeted and immunotherapies has improved the survival profiles of multiple malignancies, which has potentially altered the role of metastasectomy. This study aimed to characterize trends in metastasectomy across five primary cancers eligible for these therapies.MethodsThe National Inpatient Sample was used to identify patients who underwent metastasectomy in the United States (2016-2021). Patients with procedure codes for resection of the lung, liver, adrenal gland, brain, or small bowel and concurrent diagnosis codes for secondary malignant neoplasm of that site were included. Subjects were subcategorized by primary malignancy: colorectal cancer, lung cancer, breast cancer, melanoma, or renal cancer. Sample weights were used to produce national estimates, which were incidence adjusted by primary malignancy. Trends in utilization were calculated with average annual percent change (AAPC) and linear regression coefficients.ResultsColorectal cancer was the most frequent indication for metastasectomy (n = 57,644 cases), followed by lung cancer (n = 55,090 cases), breast cancer (n = 12,616 cases), renal cancer (n = 8427 cases), and melanoma (n = 5658 cases). Utilization of metastasectomy increased over the study period for breast cancer (AAPC, +10.6%; p = .013) and melanoma (AAPC, +8.3%; p = .040) but did not change for lung cancer (AAPC, -1.6%; p = .26), colorectal cancer (AAPC, +0.3%; p = .83), or renal cancer (AAPC, +2.3%; p = .36).ConclusionsBetween 2016 and 2021, utilization of metastasectomy increased significantly for melanoma and breast cancer. The role of metastasectomy will likely continue to develop as new treatment protocols improve survival profiles for patients with metastatic disease.

| S-EPMC11694562 | biostudies-literature

Brain metastases: lessons and challenges in the targeted therapy and immunotherapy era.

Project description: Not available

| S-EPMC7475587 | biostudies-literature

Surgical resection of metastatic melanoma in the era of immunotherapy and targeted therapy.

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

Stereotactic ablative radiotherapy versus metastasectomy for pulmonary metastases: guiding treatment in the oligometastatic era.

Project description: Not available

| S-EPMC6560524 | biostudies-literature

Lymphadenectomy in pulmonary metastasectomy.

Project description:Lymph node (LN) removal during pulmonary metastasectomy is a prerequisite to achieve complete resection or at least collect prognostic information, but is not yet generally accepted. On average, the rate of unexpected lymph node involvement (LNI) is less than 10% in sarcoma, 20% in colorectal cancer (CRC) and 30% in renal cell carcinoma (RCC) when radical LN dissection is performed. LNI is a negative prognostic factor and presence of preoperative mediastinal disease usually leads to exclusion of the patient from metastasis surgery. Nonetheless, some authors found excellent prognoses even with mediastinal LNI in colorectal and RCC metastases when radical LN dissection was performed (median survival of 37 and 36 months, respectively). Multiple metastases, central location of the lesion followed by anatomical resections are associated with a higher LNI rate. The real prognostic influence of systematic LN dissection remains unclear. Two positive effects were described after radical lymphadenectomy: a trend for improved survival in RCC patients and a reduction of mediastinal recurrences from 23% to 0% in CRC patients. Unfortunately, there is a great number of studies that do not demonstrate any positive effect of lymphadenectomy during pulmonary metastasectomy except a pseudo stage migration effect. Future studies should not only focus on survival, but also on local and LN recurrence.

| S-EPMC8107571 | biostudies-literature

Utilization of targeted near-infrared molecular imaging to improve pulmonary metastasectomy of osteosarcomas.

Project description:Pulmonary metastasectomy for osteosarcoma provides a select group of patients an opportunity for long-term survival and possible cure. Unfortunately, a complete metastasectomy is challenging due an inability to accurately identify lesions that lay below the threshold of preoperative imaging or intraoperative visual and tactile inspection. Growing evidence suggests that osteosarcomas express a number of unique molecular markers, including the folate receptor alpha. In this case report, we describe the application of a folate receptor-targeted, near-infrared optical contrast agent (OTL38) to improve osteosarcoma localization during minimally invasive pulmonary resection. In addition to localizing preoperatively identified lesions, this technology helped identify additional disease that was undetected on preoperative imaging or with traditional intraoperative techniques. This report marks the first successful utilization of a molecular imaging probe useful for osteosarcomas. This technology may provide a unique approach to improve pulmonary metastasectomy of osteosarcomas.

| S-EPMC5753425 | biostudies-literature

Pulmonary metastasectomy: an overview.

Project description:Metastasectomy is the most frequent surgical resection undertaken by thoracic surgeons, being the lung the second common site of metastases. The present oncological criteria for pulmonary metastasectomy are: (I) the primary cancer need to be controlled or controllable; (II) no extrathoracic metastasis-that is not controlled or controllable-exists; (III) all of the tumor must be resectable, with adequate pulmonary reserve; (IV) there are no alternative medical treatment options with lower morbidity. General favourable prognostic features in patients with pulmonary metastases are: (I) one or few metastases; (II) long disease free interval; (III) normal CEA levels in colorectal cancers. Negative predictive features in patients candidate to pulmonary metastasectomies are: (I) active primary cancer; (II) extrathoracic metastases; (III) inability to obtain surgical radicality; (IV) mediastinal lymphatic spread. The lack of controlled trials and studies limited by short follow-up and small cohorts did not allow to overcome some skepticism; moreover, the heterogeneity of these patients in terms of demographic, biologic and histologic characteristics represents a clear limit even in the largest series. On the basis of present knowledge, without results coming from on-going randomized trials, radical resection, histology, and disease free interval seem to be independent prognostic factors identifying a cohort of patients maximally benefitting from lung metastasectomy.

| S-EPMC5653506 | biostudies-other

Pulmonary Arterial Hypertension and Pregnancy: Single Center Experience in Current Era of Targeted Therapy.

Project description:ObjectivesTo report our experiences in pregnant patients with pulmonary arterial hypertension (PAH) who were treated with targeted therapy.MethodsFrom 2011 to 2017, women who decided to maintain pregnancies in our PAH clinic were included. Clinical data, management, and outcomes of the mothers and fetuses were reviewed.ResultsNine women with PAH and 10 deliveries were reviewed. The median maternal age was 28 (26-32) years old. The functional status of each patient was New York Heart Association functional class II or III at first visit. Sildenafil was prescribed in advance in 9 cases of delivery. Multidiscipline team approach management and intensive care were performed during the peripartum period. There was no maternal or fetal mortality. Severe cardiac events occurred in 2 patients with Eisenmenger syndrome: cardiac arrest and uncontrolled arrhythmia. Non-cardiac events occurred in 3 cases: postpartum bleeding, urinary tract infection, and pneumonia. The median gestational period at delivery was about 34 (32-38) weeks. Three cases were emergent delivery because of unexpected preterm labor. Intrauterine growth restriction developed in 4 fetuses.ConclusionsPregnancy could be maintained by the introduction of targeted therapy rather more safely than the previous era in the case of maintenance of pregnancy. Intensive care and a multidisciplinary team approach can possibly improve the outcomes of the pregnant women with PAH and their babies. However, pregnancy in patients with PAH is still strongly prohibited and it can be tried in expert center where there has sufficient multidisciplinary team approach in case of inevitability.

| S-EPMC6554588 | biostudies-literature

Long-Term Outcomes of Pulmonary Metastasectomy for Uterine Malignancies: A Multi-institutional Study in the Current Era.

Project description:BACKGROUND:Information on pulmonary metastasectomy (PM) for uterine malignancies in the current era is limited. In the present study, we analyzed the clinical course and results of PM for uterine malignancies in the era of modern imaging diagnostics to clarify the role of PM in the current era in a multi-institutional setting. METHODS:Fifty-seven patients who underwent PM for uterine malignancies between 2006 and 2015 were retrospectively reviewed. The short- and long-term outcomes, along with factors associated with the prognosis, were analyzed. Details of the clinical course after PM were described. RESULTS:The mean age of patients was 59.4 years. The primary tumor was located in the uterus corpus in 34 cases (60%) and in the uterus cervix in 23 cases (40%). The median disease-free interval (DFI) was 32 months. Forty patients (70%) received fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography before PM, and complete resection was achieved in 52 patients (91%). Postoperative complications occurred in 4 patients (7%). Of the 52 patients who underwent complete resection of pulmonary metastases, 28 experienced recurrence, and among these, 17 (60%) underwent local therapy, including six repeat PMs. Among the 52 patients who underwent complete resection, the 5-year relapse-free survival rate was 40.7% and the 5-year overall survival (OS) rate was 68.8%. The univariate analysis revealed that a DFI of ??24 months was associated with significantly poorer OS. CONCLUSIONS:PM for uterine malignancies is safe and provides favorable long-term outcomes in selected patients. Patients with a DFI of >?24 months have better OS and are good candidates for PM.

| S-EPMC7471138 | biostudies-literature

Pulmonary metastasectomy in colorectal carcinoma.

Project description:Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. It is estimated that 50% of all patients with CRC develop metastases, most commonly in the liver and the lung. Lung metastases are seen in approximately 10-15% of all patients with CRC. A large number of these patients with metastatic CRC can only receive palliative treatment due to invasion of other organs and disseminated disease. However, a subset of these patients present with potentially resectable metastases. Pulmonary metastasectomy is considered to be a potentially curative treatment for selected patients with resectable metastatic CRC. Current data suggest that patients that undergo pulmonary metastasectomy have 5-year survival rates of approximately 40%. However, the majority of data published regarding lung metastasectomy is based on small, retrospective case series. Due to this lack of prospective data, it is still unclear which subset of patients will benefit most from curative-intent surgery. Furthermore, there is also controversy regarding which prognostic and genetic factors are related to survival outcomes and whether there is a difference between open and thoracoscopic approaches in terms of overall and disease-free survival. In this review, we aim to summarize the latest data on prognostic factors and survival outcomes after pulmonary metastasectomy in patients with metastatic CRC.

| S-EPMC8107514 | biostudies-literature

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