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1.
Oxf Med Case Reports ; 2019(5): omz040, 2019 May.
Article in English | MEDLINE | ID: mdl-31198576

ABSTRACT

Osteonecrosis is a multifactorial process that can affect different skeletal structures of the body. Osteonecrosis of the jaw associated with bevacizumab, steroids and bisphosphonates, alone or in combination, is a well-documented phenomenon. There are few cases of involvement of the appendicular skeleton. Magnetic resonance imaging is the most sensitive method for diagnosis. We hereby report two cases of osteonecrosis in the right tibia and in bilateral femoral heads in patients with adenocarcinoma of the lung and ovarian papillary serous carcinoma, respectively, that developed the complication after long-term bevacizumab exposure. Long-term exposure to antiangiogenic treatment may be a potential risk factor. Oncologists should be aware that osteonecrosis is a rare but real toxicity associated with bevacizumab and other antiangiogenics, which can occur in locations different from the jaw.

2.
Lung Cancer ; 108: 238-241, 2017 06.
Article in English | MEDLINE | ID: mdl-28625643

ABSTRACT

Osimertinib is an EGFR-T790M-specific TKI, which has demonstrated impressive response rates in NSCLC, after failure to first-line anti-EGFR TKIs. However, acquired resistance to osimertinib is also observed and the molecular mechanisms of resistance are not yet fully understood. Monitoring and managing NSCLC patients who progressed on osimertinib is, therefore, emerging as an important clinical challenge. Sequential liquid biopsies were used to monitor a patient with EGFR-exon19del positive NSCLC, who received erlotinib and progressed through the acquisition of the EGFR-T790M mutation. Erlotinib was discontinued and osimertinib was initiated. Blood samples were collected at erlotinib progression and during osimertinib treatment for the detection of the activating (EGFR-exon19del) and resistance mutations (EGFR-T790M, EGFR-C797S, BRAF-V600E, METamp and ERBB2amp) in the plasma DNA using digital droplet PCR. Plasma levels of the activating EGFR-exon19del accurately paralleled the clinical and radiological progression of disease and allowed early detection of AR to osimertinib. Resistance to osimertinib coincided with the emergence of a small tumor cell subpopulation carrying the known EGFR-C797S resistance mutation and an additional subpopulation carrying amplified copies of EGFR-exon19del. Given the existence of multiple AR mechanisms, quantification of the original EGFR activation mutation, instead of the resistance mutations, can be efficiently used to monitor response to osimertinib, allowing early detection of AR. Absolute quantification of both activation and resistance mutations can provide important information on tumor clonal evolution upon progression to osimertinib. Selective amplification of the EGFR-exon19del allele may represent a novel resistance mechanism to osimertinib.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Drug Resistance, Neoplasm/genetics , ErbB Receptors/genetics , Gene Amplification , Lung Neoplasms/genetics , Mutation , Piperazines/pharmacology , Acrylamides , Alleles , Aniline Compounds , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/drug therapy , Disease Progression , Exons , Female , Humans , Liquid Biopsy , Lung Neoplasms/diagnosis , Lung Neoplasms/drug therapy , Middle Aged , Neoplasm Staging , Piperazines/therapeutic use , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Time Factors , Tomography, X-Ray Computed
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