Biological therapies in nonsmall cell lung cancer.

Biological therapies have improved survival outcomes of advanced-stage nonsmall cell lung cancer (NSCLC). Genotype-directed therapies have changed treatment paradigms of patients with EGFR-mutant and ALK/ROS1-rearranged lung adenocarcinomas, and the list of druggable targets with demonstrated clinical actionability (BRAF, MET, RET, NTRK1 and HER2) continues to expand. Furthermore, we have incrementally understood the mechanisms of cancer immune evasion and foresee ways to effectively circumvent them, particularly at the immune checkpoint level. Drugs targeting the tumour immune-evasive PD-1 pathway have demonstrated remarkable treatment benefits in this disease, with a non-negligible fraction of patients potentially receiving long-term survival benefits. Herein, we briefly discuss the role of various medical disciplines in the management of advanced-stage NSCLC and review the most relevant biological therapies for this disease, with particular emphasis in genotype-directed therapies and immune checkpoint inhibitors.

A prospective pilot study of target-guided personalized chemotherapy with intensity-modulated radiotherapy in patients with early rectal cancer.

PURPOSE: To investigate the feasibility of personalizing chemotherapy in patients with rectal cancer. METHODS: Patients with cT3 or cN1 and cM0 rectal cancer were eligible. A set of 6 molecular markers including KRAS, BRAF, and PI3K mutations and expression of topoisomerase-1 (Topo-1), ERCC-1, and thymidylate synthase (TS) using immunohistochemistry were performed in a tumor biopsy. All patients were treated with capecitabine 625 to 825 mg/m/12 h M-F in combination with either irinotecan or oxaliplatin based on Topo-1 and ERCC-1 expression plus either bevacizumab or cetuximab based on the mutation status. All patients received intensity-modulated radiation therapy. A surgery was performed 6 to 8 weeks after the treatment. RESULTS: Fifteen patients (94%) had T3 tumor and 10 (62%) N+ disease of 16 patients enrolled. In all patients, the full set of markers was analyzed within 10 days. Seven patients had K-ras mutation, and 4, 5, and 10 expressed Topo-1, ERRC-1 and TS, respectively. All patients had wild-type BRAF and PI3K tumors. The median time from obtaining informed consent to the treatment period was 18 days and all patients completed the chemoradiation treatment. Fifty percent achieved a complete pathologic response to treatment. Four patients (25%) developed grade 3 proctitis or diarrhea. There were no relevant surgical complications. Sixty-nine percent of the patients received adjuvant XELOX. CONCLUSIONS: The individualization of neoadjuvant chemotherapy in patients with rectal cancer is feasible and leads to a high rate of pathologic response.

Mycosis fungoides after solid-organ transplantation: report of 2 new cases.

Long-term survival after solid-organ transplantation is increasing because of recent advances, including new immunosuppressive regimens to avoid graft rejection. However, the resultant modification of the immune system is associated with an increased risk of several cancers. The most common are skin cancers, and lymphomas are second in frequency. Nevertheless, posttransplant primary cutaneous lymphomas (PCLs) are rare, and their incidence is not well known currently. From the files of the Nephrology and Cardiology Departments of University Hospital "12 de Octubre" of Madrid, we obtained clinical data from 1612 transplanted patients and only found 2 cases of posttransplant PCLs, both were T-cell PCL. We reviewed the clinical, histopathological, and immunohistochemical characteristics; both cases were T-cell posttransplant PCLs manifested clinically as mycosis fungoides. One was a 57-year-old woman who had received a cadaveric kidney transplant, and the other was a 60-year-old man with a heart transplant. Histology and immunohistochemistry were consistent with the features of mycosis fungoides when lesions were completely developed. Up to 20% of all organ transplant recipients will suffer some form of malignancy. Unlike general population, 70% of PCLs in transplant recipients are B cell in origin and frequently show positivity for Epstein-Barr virus markers; whereas only 30% are cutaneous T-cell lymphomas. Different pathogenic hypothesis including reduced immune surveillance, chronic antigenic stimulation by transplant grafts, and the direct oncogenic effects of immunosuppressive drugs have been suggested. Although cutaneous B-cell lymphomas are more common, dermatopathologists should be aware that cutaneous T-cell lymphomas may also appear.