ALK positive

Our study underscores the unique epidemiological profile of peripheral T-cell lymphoma in Latin America, with a high prevalence of adult T-cell leukaemia or lymphoma and extranodal natural killer T-cell lymphoma. These findings present a crucial opportunity to prioritise clinical trials on these rare subtypes of peripheral T-cell lymphoma by integrating Latin American countries into global research. However, our findings require further validation in robust epidemiological studies.

This case demonstrates the potential for ensartinib in the treatment of EML4-ALK+ lung adenocarcinoma with multiple gene mutations. Further investigation through clinical trials is needed to evaluate the safety and efficacy of this targeted therapy.

The patient's vision returned after initiation of chemotherapy. This case highlights the importance of considering malignancy in the differential for optic neuritis.

In addition, we demonstrated that brigatinib reduced the protein expression of amphiregulin, epiregulin, TGFA, PI3K, AKT and phosphorylated AKT (p-AKT). This study confirms the inhibition of HaCaT cells growth and progression by brigatinib and highlights the potential value of the PI3K/AKT pathway as a therapeutic target for brigatinib-induced dermal toxicities.

This is the first investigation to explore the impact of circulating anti-ALK a-abs on BM. Prospective studies with longer follow-up are warranted to further explore the impact of anti-ALK a-abs on BM.

ctDNA testing to detect oncogenic fusions or METexon14 mutations in advanced NSCLC patients is useful, even if type of gene alterations and clinical characteristics could influence the driver detection rate. Liquid biopsy represents a complementary tool to tissue genotyping, however more sensitive approaches for gene fusions and METexon14 detection are needed to implement its strength and reliability.

After 5 years of follow-up, lorlatinib efficacy and safety in the Asian subgroup of CROWN continue to be consistent with those in the overall population, with PFS remaining unreached with lorlatinib.

Subsequently, she underwent laparoscopic partial cystectomy using the Signia Stapling System due to the low-grade malignancy of the tumor. The patient has been under outpatient observation with no recurrence for 12 months post-surgery.

Brigatinib was demonstrated to be a safe and effective treatment option for ALK-positive metastatic non-small cell lung cancer in routine clinical practice in Argentina.

P1, N=150, Recruiting, Ascentage Pharma Group Inc. | Trial completion date: Feb 2025 --> Jan 2028 | Trial primary completion date: Jan 2025 --> Dec 2027

P2, N=26, Recruiting, Pingping Song | Not yet recruiting --> Recruiting | Trial completion date: Jul 2025 --> Apr 2028 | Trial primary completion date: Mar 2025 --> Jan 2026

We present FDG PET/CT findings in a pediatric patient with ALK-positive histiocytosis isolated to the left nasal cavity. The nasal cavity tumor invaded the nasal septum, left nasal bone, and left ethmoid sinus and showed intense FDG activity with an SUVmax of 9.9.

When we investigated the effect of the combination of alectinib and SHP099 in these novel 3D cultures, we found a comparable cellular response compared with our two-dimensional experiments especially with the drugs in combination. We suggest that 3D cultures be used as preclinical screening platforms to ensure that only the most efficacious drug candidates move on to in vivo testing.

A FUS (exon 7)::CREM (exon 6) fusion was detected in two tumors and confirmed by FISH. This paraganglioma-like malignant neoplasm may belong to the group of FET::CREB-rearranged mesenchymal neoplasms, currently in the course of delineation, and points to its phenotypic diversity.

The presence of perirenal lymph node metastases and recurrence despite nephrectomy is indicative of the poor prognosis of this tumor. Further investigation of the relationship between the loss of SMARCB1 protein and the development of RCCU-MP might improve our understanding of the pathogenesis of this malignant tumor.

In recent years, systemic therapies such as trastuzumab deruxtecan and tucatinib have been reported effective for human epidermal growth factor receptor 2 (HER2)-positive breast cancer, however, these cannot be used for all MC. In the future, if a lineup of highly effective systemic therapies such as tyrosine kinase inhibitors for ALK gene-positive lung cancer is established, treatment strategies for MC may change. However at present, rapid diagnosis and prompt neurological palliative treatment play an important role in the neurological symptoms management of MC.

Early recognition and prompt intervention are crucial to mitigate renal complications and optimize patient outcomes. Brigatinib may serve as a suitable alternative for patients intolerant to alectinib.

The activation of downstream pathways and the response to ALK inhibitors crizotinib and alectinib were demonstrated by western blotting (WB). We identified and functionally validated PLCXD3-ALK as a novel rare fusion in NSCLC that has not been previously reported. It can serve as a meaningful therapeutic target for ALK inhibitors of ALK + NSCLC.

This case underscores the aggressive nature of pediatric ALCL with complex karyotypes and highlights the challenges associated with its treatment. Despite intensive chemotherapy, the disease exhibited rapid relapse and resistance, ultimately leading to a fatal outcome. This report contributes to the limited literature on pediatric ALCL, particularly in cases with complex cytogenetic profiles, and emphasizes the need for novel thera-peutic approaches and early intervention strategies.

P2, N=48, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2024 --> Aug 2025

The patient developed resistance to Lorlatinib treatment accompanied by mesenchymal-epithelial transition factor (MET) amplification. Effective tumor control was achieved with the combined use of Crizotinib and Lorlatinib, providing a valuable reference for further exploration of treatment strategies following resistance to ALK-TKIs in clinical practice..

Alectinib has emerged as a viable, significantly superior treatment option for patients with ALK-positive NSCLC. The superior efficacy and manageable safety profile are significant; it remains a novel therapy with much potential, such as neoadjuvant therapy, which will make significant strides in patient care of ALK-positive NSCLC. Therefore, it is crucial for healthcare professionals, including surgeons, to be well-versed in alectinib and its potential. This knowledge will empower them and instill confidence in their ability to provide the best care for their patients.

No abstract available

P=N/A, N=600, Recruiting, Pfizer | Trial completion date: Aug 2028 --> Mar 2028 | Trial primary completion date: Aug 2028 --> Mar 2028

However, in previous studies, patients with ALK (Anaplastic Lymphoma Kinase) rearranged had a low response to immune checkpoint inhibitor (ICI) and the role of immunotherapy in ALK-positive NSCLC patients is unclear. Here, we report a case of a young man with ALK rearranged who demonstrated a complete response to anti-PD1 combination with chemotherapy, which suggests some ALK-rearranged patients with high expression of PD-L1 may permanently benefit from immunotherapy.

Enriched KEGG pathways included the MAPK, PI3K-Akt, and Ras signaling. This pharmacovigilance study identifies significant AE signals linking ALK TKIs to liver injury, highlighting potential mechanisms and providing insights for clinical management and patient outcomes.

Further experimental validation yielded that NSCLC with deleted BIM genes were less sensitive to aleitinib. BIM gene deletion can increase resistance to alectinib, and the potential efficacy of a combination of BIM sensitizer and alectinib to overcome alectinib resistance can be explored.

PD-L1 positivity is common in ALK-positive lung cancer patients and correlates with poorer prognosis. PD-L1 serves as an independent predictor of adverse outcomes, indicating its potential as a biomarker for assessing lung cancer severity and prognosis.

Alectinib and brigatinib demonstrated comparable efficacy in ALK-positive advanced NSCLC. Undergoing crizotinib followed by a second-generation TKI was not significantly different from initiating a second-generation TKI without prior crizotinib in terms of outcomes.

The patient's condition improved following occupational rehabilitation therapy for right upper motor weakness, as well as anticonvulsant and radiation therapy, and her neurological condition remains stable. This case underscores the diagnostic challenges of Histiocytic Neoplasms and the necessity for interdisciplinary collaboration and sophisticated diagnostic techniques.

Immunohistochemical detection of PD-L1 expression in malignant pleural fluid of advanced NSCLC provides a basis for clinical tumor immunotherapy. Immunohistochemical detection of PD-L1 expression in malignant pleural fluid of advanced NSCLC is minimally invasive, simple, and fast, particularly for metastatic NSCLC where malignant pleural fluid is the first symptom, offering significant clinical application value.

No abstract available

No abstract available

The tumor was completely excised with negative margins. The patient is doing well at 17 months follow-up with no signs of recurrence.

In addition to reporting the identification of a novel ALK fusion, XPO1-ALK (intergenic), and the sensitivity and safety of brigatinib treatment for lung cancer, this study increased the list of known ALK fusion partners in ALK-positive NSCLC. This case report has a significant clinical reference.

For patients with ALK-positive SCLC, ALK inhibitors may be a reliable treatment option.

The patient experienced progression on initial iruplinalkib and subsequent alectinib therapy within 5 months. After the failure of third-line therapy with cisplatin-pemetrexed combined with bevacizumab, she received sintilimab plus anlotinib which led to a progression-free survival of 6.5 months. She received sintilimab combined with albumin-paclitaxel plus carboplatin and achieved partial response after 6 months...After progression on ICB-based therapy, the patient was treated with lorlatinib and still under follow-up with overall survival of more than 3 years. Our findings highlight the therapeutic potential of ICB-based regimens in patients with MSI-H and ALK-rearranged NSCLC.

The patient received three cycles of an "alectinib + Vincristine + Rituximab + Cyclophosphamide + Doxorubicin (VRCD) " regimen. In the fourth cycle, brentuximab vedotin monoclonal antibody treatment was added to increase the efficacy of the treatment...Thus far, the patient has undergone six treatment cycles and successfully received autologous hematopoietic stem cell transplantation. Currently, the patient is receiving maintenance therapy with alectinib and lenalidomide and remains in a favorable clinical condition.

We present the case of a 65-year-old male patient with anaplastic lymphoma kinase-positive lung cancer and preexisting type 2 diabetes mellitus who developed diabetic ketoacidosis (DKA) after switching from alectinib to lorlatinib. After a 2-week interruption, lorlatinib was resumed at a reduced dose with satisfactory glycemic control. This case highlights the importance of vigilant glucose monitoring for patients receiving lorlatinib, especially those with preexisting diabetes, to prevent life-threatening complications such as DKA.

P1, N=244, Recruiting, AbbVie | N=128 --> 244 | Trial completion date: Apr 2029 --> Mar 2031 | Trial primary completion date: Jun 2027 --> Mar 2031

FDA-approved NTRK inhibitors entrectinib and larotrectinib effectively blocked TG::NTRK1 signaling in vitro and inhibited xenograft tumor growth in vivo. In summary, we report a spectrum of TG gene fusions as recurrent oncogenic events in thyroid cancer and NIFTP that drive strong overexpression of partner genes, frequently RTKs. The TG::NTRK1 fusion is prone to dimerization, activates oncogenic signaling, drives tumorigenesis in thyroid cells, and, like other fusions involving RTKs, represents a potential therapeutic target in thyroid cancer.

This case underscores the importance of considering primary cutaneous ALCL in the differential diagnosis of persistent ulcerative lesions in anatomically sensitive areas. Early diagnosis, multidisciplinary management, and advanced therapeutic strategies such as Brentuximab Vedotin + Cyclophosphamide, Hydroxyrubicin, and Prednisone (BV + CHP) are critical to optimizing outcomes in this rare presentation.