Path Less Traveled: Targeting Rare Driver Oncogenes in Non-Small-Cell Lung Cancer.

Over the past decade, tremendous efforts have been made in the development of targeted agents in non-small-cell lung cancer (NSCLC) with nonsquamous histology. Pivotal studies have used next-generation sequencing to select the patient population harboring oncogenic driver alterations that are targetable with targeted therapies. As treatment paradigm rapidly evolves for patients with rare oncogene-driven NSCLC, updated comprehensive overview of diagnostic approach and treatment options is paramount in clinical settings. In this review article, we discuss the epidemiology, molecular testing, and landmark clinical trials addressing the targeted agents for ROS1 rearrangement, METex14 skipping mutation, EGFR exon 20 insertion, KRAS G12C mutation, HER2 mutation, RET fusion, NTRK fusion, and BRAF mutations.

Management of HER2 alterations in non-small cell lung cancer - The past, present, and future.

HER2 mutations, which account for 2-4% of non-small cell lung cancer (NSCLC), are distinct molecular alterations identified via next generation sequencing (NGS). Previously, treatment outcomes in HER2-mutant metastatic NSCLC were dismal, showing limited clinical benefit with platinum-based chemotherapy with or without immunotherapy. In contrast to HER2-altered breast and gastric cancer, HER2-mutant NSCLC does not benefit from HER2 targeting agents such as trastuzumab or TDM1. HER2 mutations are also inherently different from HER2 overexpression and amplification. Currently, trastuzumab deruxtecan, a HER2 targeting antibody drug conjugate (ADC) is the first and only approved treatment option for patients with HER2-mutant metastatic NSCLC after failure with standard treatment. In this review, we summarized the biology of HER2 and detection of HER2 overexpression, amplification and mutations, as well as general landscape of landmark and ongoing clinical trials encompassing from chemotherapy to targeted agents, including tyrosine kinase inhibitors (TKIs), ADCs and investigational agents.

Early Revision Surgery for Tibial Plateau Fractures.

OBJECTIVE: To describe patients' outcomes after revision of tibial plateau fracture fixation within 12 months of the initial surgical procedure. To assess differences in objective outcome scores [International Knee Documentation Committee (IKDC), short form-36, arthrosis score, physical examination] depending on whether patients were treated for malreduction, malunion, or nonunion. DESIGN: Retrospective case series. PATIENTS: Twenty-seven patients who underwent revision within 1 year of primary surgery and with a minimum follow-up of 1 year. MAIN OUTCOME MEASUREMENT: IKDC Subjective Knee Form, alignment, osteoarthritis, timed up and go test, range of motion, and physical and mental health (using the short form-36 survey). RESULTS: At the most recent follow-up, the mean IKDC subjective knee score of all patients within the study group was 62 (SD 17). In the malreduction group, the mean was 71 (SD 17), in the malunion group the mean was 56 (SD 17), and in the nonunion group, the mean was also 56 (SD 12; χ 0.94; P = 0.624). Comparing the malreduction group with the malunion and nonunion groups combined, there was a significantly higher IKDC score (P = 0.019) in the malreduction group. CONCLUSION: A suboptimal outcome after open reduction and internal fixation of a tibial plateau fracture is common. If the underlying cause of the fracture is malreduction, malunion, or a nonunion, salvage of the joint without a knee replacement is worthwhile. When using a strategy incorporating revision plate fixation, osteotomy (intra- and/or extraarticular), debridement, and bone grafting when needed, patients should experience favorable long-term outcomes, including less residual pain and functional limitations. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Waking up the healing potential of the bone:subtrochanteric non-union in femoral dysplasia successfully treated after 40 years of pain and disability.

We describe a successful valgus osteotomy for a subtrochanteric non-union in a dysplastic femur that had not healed in 40 years despite many earlier attempts. The optimisation of biology and biomechanics in the subtrochanteric area shows that even in a longstanding and complex deformity around the hip salvage is possible.