- Immune checkpoint inhibitors in non-small cell lung cancer (NSCLC): Approaches on special subgroups and unresolved burning questions. [Review]
- CTCancer Treat Rev 2018 Feb 08; 64:21-29
- Immune checkpoint inhibitors (ICIs) have been incorporated in the treatment strategy of advanced non-small cell lung cancer (NSCLC). Beyond the already approved indications in first- and second-line ...
Immune checkpoint inhibitors (ICIs) have been incorporated in the treatment strategy of advanced non-small cell lung cancer (NSCLC). Beyond the already approved indications in first- and second-line setting of advanced NSCLC, new data has recently emerged demonstrating its efficacy in locally advanced disease as maintenance after chemo-radiotherapy and currently several trials are also exploring its efficacy in earlier stages of the disease to evaluate whether these results could be extrapolated to the adjuvant setting. With the advent of all these new therapies, their potential in other thoracic malignancies such as mesothelioma and small-cell lung cancer are also being evaluated with encouraging preliminary data that endorses their short-term incorporation as new therapeutic options in these thoracic malignancies. However, despite all these new evidence, there are still several open questions that remain to be solved like the use of immune agents in special subpopulations such as elderly or fragile patients or the case of patients with brain metastases or autoimmune disorders. In addition some other open questions remain with regards ICIs activity in patients receiving corticosteroid or antibiotics, the potential use in oncogenic addicted tumours, as well as the safety of retreatment after the onset of immune-related adverse events (ir-AE) or the optimal dose schedule or time on treatment for ICIs administration. Herein, we propose to address all these questions, reviewing most recent evidence available in order to give readers some practical advises and guidance on how to deal with these challenges when treating NSCLC patients with immunotherapy.
- Phase 1b study of pasireotide, everolimus, and selective internal radioembolization therapy for unresectable neuroendocrine tumors with hepatic metastases. [Journal Article]
- CCancer 2018 Feb 16
- CONCLUSIONS: The recommended phase 2 dose of everolimus is 10 mg daily in combination with pasireotide and SIRT. The regimen is well tolerated. Preliminary activity appears promising. Cancer 2018. © 2018 American Cancer Society.
- The brigatinib experience: a new generation of therapy for ALK-positive non-small-cell lung cancer. [Journal Article]
- FOFuture Oncol 2018 Feb 16
- Lung cancer remains the leading cause of cancer deaths in the world with 1.69 million deaths in 2015. A total of 85% of lung cancer cases are non-small-cell lung cancers (NSCLCs). Driver mutations as...
Lung cancer remains the leading cause of cancer deaths in the world with 1.69 million deaths in 2015. A total of 85% of lung cancer cases are non-small-cell lung cancers (NSCLCs). Driver mutations associated with anaplastic lymphoma kinase (ALK) have been identified in a variety of malignancies, including NSCLC. An ALK inhibitor (crizotinib, ceritinib and alectinib) is the preferred therapeutic approach to those advanced ALK fusion variant-positive NSCLC patients. Brigatinib, a next-generation ALK inhibitor, shows promising activity in ALK-rearranged NSCLC that have previously received crizotinib with response rates in ALTA ranging from 42-50%, intracranial response 42-67% and median progression-free survival 9.2-12.9 months. Randomized Phase III trial, ALTA-1 L is investigating brigatinib in ALK inhibitor-naive patients.
- Real-life experience of ceritinib in crizotinib-pretreatedALK+advanced non-small cell lung cancer patients. [Journal Article]
- EOERJ Open Res 2018; 4(1)
- Here we report our experience of ceritinib in crizotinib-pretreated patients with anaplastic lymphoma kinase (ALK) positive (ALK+) non-small cell lung cancer (NSCLC) in a French temporary authorisati...
Here we report our experience of ceritinib in crizotinib-pretreated patients with anaplastic lymphoma kinase (ALK) positive (ALK+) non-small cell lung cancer (NSCLC) in a French temporary authorisation for use (TAU) study. The French TAU study included crizotinib-pretreated patients with advancedALK+or ROS proto-oncogene 1 positive (ROS1+) tumours. Patients received oral ceritinib (750 mg·day-1as a starting dose) and best tumour response (as evaluated by the investigator) and safety were reported every 3 months. A total of 242 TAUs were granted from March 12, 2013 to August 05, 2015. Of the 242 patients, 228 hadALK+NSCLC and 13 hadROS1+NSCLC. The median age ofALK+patients (n=214) was 58.5 years, 51.9% were female, 70.8% had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 and 50.0% had brain metastases. Of the 149 efficacy evaluableALK+NSCLC patients, 5.4% had a complete response (CR), 47.0% had a partial response (PR) and 22.8% had stable disease (SD). At September 05, 2015, the median duration of ceritinib treatment (n=182) was 3.9 months but 5.5 months for patients (n=71) with a follow-up of ≥12 months. Higher objective response rate (ORR) was observed for patients with ECOG PS 0 to 1 (55.0%versus42.4%) and those receiving prior crizotinib for >5 months (51.6%versus36.1%). Treatment-related adverse events (AEs) were reported in 118 of 208 patients (56.7%), the most common being diarrhoea (22.1%) and hepatic toxicity (19.7%). Ceritinib (750 mg·day-1) demonstrated efficacy similar efficacy to ASCEND-1, ASCEND-2 and phase 3 ASCEND-5 trials with manageable safety in crizotinib-pretreated patients withALK+NSCLC.
- Targeted therapy of brain metastases: latest evidence and clinical implications. [Review]
- TATher Adv Med Oncol 2017; 9(12):781-796
- Brain metastases (BM) occur in 20-40% of patients with cancer and 60-75% of patients with BM become symptomatic. Due to an aging population and advances in the treatment of primary cancers, patients ...
Brain metastases (BM) occur in 20-40% of patients with cancer and 60-75% of patients with BM become symptomatic. Due to an aging population and advances in the treatment of primary cancers, patients are living longer and are more likely to experience complications from BM. The diagnosis of BM drastically worsens long-term survival rates, with multiple metastases being a poor prognostic factor. Until recently, the mainstay of treatment consisted of stereotactic radiosurgery (SRS), surgical resection, whole brain radiation therapy (WBRT), or a combination of these modalities. Systemic chemotherapy has been felt largely ineffective in the treatment of BM due to the presence of the blood-brain barrier (BBB), which includes efflux pumps on brain capillaries. Over the past decade however, researchers have identified therapeutic agents that are able to cross the BBB. These findings could make a multimodality treatment approach possible, consisting of surgery, radiation, immunotherapy, and targeted therapy, which could lead to better disease control in this patient population and prolong survival. In this review, we discuss present evidence on available targeted therapies and their role in the treatment of BM from primary tumors with the highest prevalence of central nervous system (CNS) involvement, specifically non-small cell lung cancer (NSCLC), breast cancer melanoma, and renal cell carcinoma.
- Dedifferentiated primary mediastinal liposarcoma mimicking a thymic tumor. [Journal Article]
- PPathologica 2017; 109(4):401-404
- Mediastinal tumors are heterogeneous and the diagnosis depends on their location in the mediastinum. The most frequent tumors are germinal tumor, lymphoma and thymoma. The clinical and radiological a...
Mediastinal tumors are heterogeneous and the diagnosis depends on their location in the mediastinum. The most frequent tumors are germinal tumor, lymphoma and thymoma. The clinical and radiological aspects are often not sufficient to orient the diagnosis and biopsy is necessary to confirmed it. Here, we present a rare case of an anterior mediastinal mass incidentally detected in a 63 years old man during assessment for asthma. The lesion was presumptively diagnosed as a thymic epithelial tumor based on location and radiological characteristics. Surgical biopsy revealed a primary dedifferentiated mediastinal liposarcoma with multiple lung metastases.
- Metaplastic breast cancer in a patient with neurofibromatosis type 1 and somatic loss of heterozygosity. [Journal Article]
- CSCold Spring Harb Mol Case Stud 2018 Feb 15
- Metaplastic breast carcinoma (MBC) is rare and has a poor prognosis. Here we describe genetic analysis of a 41-year-old female patient with MBC and neurofibromatosis type I (NF1). She initially prese...
Metaplastic breast carcinoma (MBC) is rare and has a poor prognosis. Here we describe genetic analysis of a 41-year-old female patient with MBC and neurofibromatosis type I (NF1). She initially presented with pT3N1a, grade 3 MBC, but lung metastases were discovered subsequently. To identify the molecular cause of her NF1, we screened for germline mutations disrupting NF1 or SPRED1, revealing a heterozygous germline single nucleotide variant (SNV) in exon 21 of NF1 at c.2709G>A, chr17: 29556342. By report, this variant disrupts pre-mRNA splicing of NF1 transcripts. No pathogenic mutations were identified in SPRED1. A potential association between MBC and NF1 was reported in 8 previous cases, but none underwent detailed genomics analysis. To identify additional candidate germline variants potentially predisposing to MBC, we conducted targeted exome sequencing of 279 established cancer-causing genes in a control blood sample, disclosing 4 rare SNVs. Analysis of her breast tumor showed markedly altered variant allelic fractions (VAFs) for 2 (50%) of them, revealing somatic loss of heterozygosity (LOH) at germline SNVs. Of these, only the VAF of the pathogenic SNV in NF1 was increased in the tumor. Tumor sequencing demonstrated 5 somatic mutations altering TP53, BRCA1 and other genes potentially contributing to cancer formation. Since somatic LOH at certain germline SNVs can enhance their impacts, we conclude that increased allelic imbalance of the pathogenic SNV in NF1 likely contributed to tumorigenesis. Our results highlight a need to assess predisposing genetic factors and LOH that can cause rare, aggressive diseases such as MBC in NF1.
- E-cadherin Loss Accelerates Tumor Progression and Metastasis in a Mouse Model of Lung Adenocarcinoma. [Journal Article]
- AJAm J Respir Cell Mol Biol 2018 Feb 15
- Metastatic disease is the primary cause of death of lung cancer patients, but the mouse models of lung adenocarcinoma do not accurately recapitulate the tumor microenvironment or metastatic disease o...
Metastatic disease is the primary cause of death of lung cancer patients, but the mouse models of lung adenocarcinoma do not accurately recapitulate the tumor microenvironment or metastatic disease observed in patients. In this study, we conditionally deleted E-cadherin in an autochthonous lung adenocarcinoma mouse model driven by activated oncogenic Kras and p53 loss. Loss of E-cadherin significantly accelerated lung adenocarcinoma progression and decreased survival of the mice. Kras;p53;E-cadherin mice had a 41% lung tumor burden, invasive grade 4 tumors, and a desmoplastic stroma just 8 weeks after tumor initiation. 100% of the mice developed local metastases to the lymph nodes or chest wall and 38% developed distant metastases to the liver or kidney. Lung adenocarcinoma cancer cell lines derived from these tumors also had high migratory rates. These studies demonstrate that the Kras;p53;E-cadherin mouse model better emulates the tumor microenvironment and metastases observed in human lung adenocarcinoma patients and may therefore be useful for studying metastasis and testing new lung cancer treatments in vivo.
- Uniportal video-assisted thoracoscopic surgery (VATS) sleeve resections for non-small cell lung cancer patients: an observational prospective study and technique analysis. [Journal Article]
- JVJ Vis Surg 2018; 4:16
- Bronchus sleeve resection for operative treatment of non-small cell lung cancer (NSCLC) is a gold standard in modern thoracic surgery in cases of centrally located tumors or hilär lymph node metastas...
Bronchus sleeve resection for operative treatment of non-small cell lung cancer (NSCLC) is a gold standard in modern thoracic surgery in cases of centrally located tumors or hilär lymph node metastases. Advanced instruments and growing surgical experience allowed surgeons to reduce the required incisions (from 3-port to uniportal) and to resect larger and more centrally located malignancies minimal invasively. It is a logical and expected advance in thoracic surgery that video-assisted thoracoscopic surgery (VATS) would be ultimately used also for complex bronchial resections. We therefore present in this study our early clinical results and technique of uniportal sleeve resections for patients with centrally located NSCLC or carcinoids. In the period 2015-2017, n:40 patients with NSCLC were found eligible for uniportal VATS sleeve resection in our institution. In two cases a thoracotomy conversion because of severe hilar scar tissue was necessary. In 38 cases a uniportal VATS sleeve resection could be completed. We believe that uniportal sleeve resections are the logical evolution of VATS allowing patients with locally advanced malignancies to have quicker recovery and reduced perioperative pain.
New Search Next
- The growing importance of lesion volume as a prognostic factor in patients with multiple brain metastases treated with stereotactic radiosurgery. [Journal Article]
- CMCancer Med 2018 Feb 14
- Stereotactic Radiosurgery (SRS) is considered standard of care for patients with 1-3 brain metastases (BM). Recent observational studies have shown equivalent OS in patients with 5+ BM compared to th...
Stereotactic Radiosurgery (SRS) is considered standard of care for patients with 1-3 brain metastases (BM). Recent observational studies have shown equivalent OS in patients with 5+ BM compared to those with 2-4, suggesting SRS alone may be appropriate in these patients. We aim to review outcomes of patients treated with SRS with 2-4 versus 5+ BM. This analysis included consecutive patients from 1994 to 2015 treated with SRS. Of 1017 patients, we excluded patients with a single BM and patients without adequate survival data, resulting in 391 patients. All risk factors were entered into univariate analysis using Cox proportional hazards model, and significant factors were entered into multivariate analysis (MVA). We additionally analyzed outcomes after excluding patients with prior surgery or whole-brain radiotherapy (WBRT). Median follow-up was 7.1 months. Median KPS was 90, mean age was 59, and most common histologies were melanoma and lung. Median tumor volume was 3.41 cc. Patients with 2-4 BM had a median OS of 8.1 months compared to 6.2 months for those with 5+ BM (P = 0.0136). On MVA, tumor volume, KPS, and histology remained significant for OS, whereas lesion number did not. Similar results were found when excluding patients with prior surgery or WBRT. Rather than lesion number, the strongest prognostic factors for patients undergoing SRS were tumor volume >10 cc, KPS, and histology. BM number may therefore not be the most important criterion for candidacy for SRS. Patients with more 5+ BM should be considered for SRS.