Acquired drug resistance conferred by a KRAS gene mutation following the administration of cetuximab: a case report

BACKGROUND: Although a number of studies have reported acquired drug resistance due to administration of epidermal growth factor receptor antibody inhibitors, the underlying causes of this phenomenon remain unclear. CASE PRESENTATION: Here we report a case of a 75-year-old man with liver metastasis at 3 years after a successful transverse colectomy to treat KRAS wild-type colorectal cancer. While initial administration of epidermal growth factor receptor inhibitors proved effective, continued use of the same treatment resulted in new peritoneal seeding. An acquired KRAS mutation was found in a resected tissue specimen from one such area. This mutation, possibly caused by administration of epidermal growth factor receptor inhibitors, appears to have conferred drug resistance. CONCLUSION: The present findings suggest that administration of epidermal growth factor receptor inhibitors results in an acquired KRAS mutation that confers drug resistance

Prognostic significance of tumor size of small lung adenocarcinomas evaluated with mediastinal window settings on computed tomography.

BACKGROUND:We aimed to clarify that the size of the lung adenocarcinoma evaluated using mediastinal window on computed tomography is an important and useful modality for predicting invasiveness, lymph node metastasis and prognosis in small adenocarcinoma. METHODS:We evaluated 176 patients with small lung adenocarcinomas (diameter, 1-3 cm) who underwent standard surgical resection. Tumours were examined using computed tomography with thin section conditions (1.25 mm thick on high-resolution computed tomography) with tumour dimensions evaluated under two settings: lung window and mediastinal window. We also determined the patient age, gender, preoperative nodal status, tumour size, tumour disappearance ratio, preoperative serum carcinoembryonic antigen levels and pathological status (lymphatic vessel, vascular vessel or pleural invasion). Recurrence-free survival was used for prognosis. RESULTS:Lung window, mediastinal window, tumour disappearance ratio and preoperative nodal status were significant predictive factors for recurrence-free survival in univariate analyses. Areas under the receiver operator curves for recurrence were 0.76, 0.73 and 0.65 for mediastinal window, tumour disappearance ratio and lung window, respectively. Lung window, mediastinal window, tumour disappearance ratio, preoperative serum carcinoembryonic antigen levels and preoperative nodal status were significant predictive factors for lymph node metastasis in univariate analyses; areas under the receiver operator curves were 0.61, 0.76, 0.72 and 0.66, for lung window, mediastinal window, tumour disappearance ratio and preoperative serum carcinoembryonic antigen levels, respectively. Lung window, mediastinal window, tumour disappearance ratio, preoperative serum carcinoembryonic antigen levels and preoperative nodal status were significant factors for lymphatic vessel, vascular vessel or pleural invasion in univariate analyses; areas under the receiver operator curves were 0.60, 0.81, 0.81 and 0.65 for lung window, mediastinal window, tumour disappearance ratio and preoperative serum carcinoembryonic antigen levels, respectively. CONCLUSIONS:According to the univariate analyses including a logistic regression and ROCs performed for variables with p-values of <0.05 on univariate analyses, our results suggest that measuring tumour size using mediastinal window on high-resolution computed tomography is a simple and useful preoperative prognosis modality in small adenocarcinoma

Permissible Outcomes of Lobe-Specific Lymph Node Dissection for Elevated Carcinoembryonic Antigen in Non-Small Cell Lung Cancer

Background and Objectives: Lobe-specific nodal dissection (L-SND) is currently acceptable for the dissection of early-stage non-small cell lung cancer (NSCLC) but not for cancers of more advanced clinical stages. We aimed to assess the efficacy of L-SND, compared to systemic nodal dissection (SND). Materials and Methods: We retrospectively collected the clinical data of patients with carcinoembryonic antigen (CEA) abnormality who underwent complete resection of NSCLC via lobectomy or more in addition to either SND or L-SND at two cancer-specific institutions from January 2006 to December 2017. Results: A total of 799 patients, including 265 patients who underwent SND and 534 patients who underwent L-SND, were included. On multivariate analysis, thoracotomy, more than lobectomy, cN1-2, advanced pathological stage, adjuvant treatment, and EGFR or ALK were strongly associated with SND. No significant differences were found in overall survival, disease-free survival, and overtime survival after propensity adjustment (p = 0.09, p = 0.11, and p = 0.50, respectively). There were no significant differences in local (p = 0.16), regional (p = 0.72), or distant (p = 0.39) tumor recurrence between the two groups. Conclusions: SND did not improve the prognosis of NSCLC patients with CEA abnormality. Complete pulmonary resection via L-SND seems useful for NSCLC patients with CEA abnormality

Preoperative prognostic factors for disease-free survival with small adenocarcinomas (≤3 cm).

<p>Logistic regression test (Univariate analyses).</p><p>LD: diameter using lung window setting, MD: diameter using mediastinal window setting, RFS: recurrence-free survival, TDR: tumour disappearance ratio (TDR  = 1− MD/LD), CEA: carcinoembryonic antigen, cN: preoperative nodal status, CI: confidence interval.</p><p>Preoperative prognostic factors for disease-free survival with small adenocarcinomas (≤3 cm).</p

Receiver operating characteristic analyses for lymph node metastasis.

<p>Tumour dimension was evaluated using lung window (LD) and mediastinal window (MD) settings. TDR: tumour disappearance ratio (TDR  = 1− MD/LD), CEA: carcinoembryonic antigen. Allow indicated a value at 100% sensitivity.</p

Receiver operating characteristic analyses for recurrence.

<p>Tumour dimension was evaluated using lung window (LD) and mediastinal window (MD) settings. TDR: tumour disappearance ratio (TDR  = 1− MD/LD). Allow indicated a value at 100% sensitivity.</p

Incidence of lymphatic vessel, vascular vessel or pleural invasion in small adenocarcinomas according to tumour dimension using mediastinal window (MD) settings.

<p>A black bar showed a patient with invasion to any of lymphatic vessel, vascular vessel or pleura, and a gray bar showed a patient without any of them.</p

Preoperative factors associated with lymph node metastasis in small adenocarcinoma (≤3 cm).

<p>Logistic regression test (Univariate analyses).</p><p>LD: diameter by lung window setting, MD: diameter by mediastinal window setting, TDR: tumour disappearance ratio (TDR  = 1− MD/LD), CEA: carcinoembryonic antigen, cN: preoperative nodal status, CI: confidence interval, LN: lymph node.</p><p>Preoperative factors associated with lymph node metastasis in small adenocarcinoma (≤3 cm).</p