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Duration of Adjuvant Endocrine Therapy for Breast Cancer
For postmenopausal women receiving adjuvant treatment with an aromatase inhibitor (AI) for hormone-positive breast cancer, the standard duration of treatment has been five years. However, data from the MA17R trial demonstrated that a longer course of treatment improves disease-free survival (DFS). Among approximately 1900 postmenopausal women who had completed four and a half to six years of therapy with an AI, treatment for an additional five years improved five-year DFS relative to those who received placebo (95 versus 91 percent). There was no difference between the groups in regards to overall survival. Bone-related toxic effects were more frequent among those receiving extended treatment. Based on these results, we now offer an additional five years of treatment to those who have completed five years of AI therapy. However, it is reasonable for women with low risk of recurrence who are concerned about the risks and toxicities of extended treatment to omit extended treatment after a risk-benefit discussion.
Role of Endometrial Sampling in Preoperative Diagnosis of Uterine Sarcoma
Uterine sarcoma is a rare and aggressive malignancy, with few reliable methods for preoperative diagnosis. In a recent study including 68 women with leiomyosarcoma who underwent endometrial sampling before surgery, the sensitivity of the test for diagnosis of features of a smooth muscle malignancy was 52 percent (leiomyosarcoma: 35 percent, spindle cell or other features suspicious for malignancy: 16 percent). There was no significant difference in test performance between office endometrial biopsy and dilation and curettage. We suggest endometrial sampling for women with a uterine mass and signs, symptoms, risk factors, or other findings that raise suspicion of uterine sarcoma or endometrial carcinoma or for women in whom planned surgical treatment includes intraperitoneal morcellation.
Radiation Plus Temozolomide in Older Adults With Glioblastoma
Shorter courses of radiation are increasingly used to treat older adults with glioblastoma, but the safety and efficacy of temozolomide in combination with such regimens have not been well studied. In a multinational phase III trial, 562 adults ≥65 years of age with a good performance status were randomly assigned to receive hypofractionated radiation (40 Gy in 15 fractions) plus concurrent and adjuvant temozolomide or radiation alone. Overall survival was significantly prolonged in patients assigned to combination therapy (9.3 versus 7.6 months), and quality of life outcomes were similar aside from an increase in nausea and constipation related to chemotherapy. The addition of temozolomide was especially beneficial in the subset of patients with O-6-methylguanine-DNA methyltransferase (MGMT) methylated tumors (13.5 versus 7.7 months).
Role of Cabazitaxel in Castration-Resistant Prostate Cancer
Cabazitaxel, a semisynthetic taxane derivative, was developed for its activity in patients with prostate cancer and resistance to docetaxel. Cabazitaxel was initially approved at a dose of 25 mg/m2 every three weeks based upon phase III results demonstrating improved overall survival compared with mitoxantrone in patients who had previously progressed on docetaxel. Two subsequent phase III trials of cabazitaxel were presented at the 2016 American Society of Clinical Oncology (ASCO) meeting. In a noninferiority trial, men who had progressed on docetaxel were randomly assigned to cabazitaxel at a dose of either 20 or 25 mg/m2. The lower dose met predefined noninferiority criteria for overall survival and was associated with significantly less toxicity. In a trial in patients with castration-resistant prostate cancer, initial chemotherapy with cabazitaxel did not improve overall survival compared with docetaxel. Cabazitaxel at a dose of 20 mg/m2 is now the preferred cytotoxic chemotherapy for patients who have progressed on docetaxel while docetaxel remains the recommended agent for patients who are chemotherapy-naïve.
Potential Mechanism of Malignancy-Associated Membranous Nephropathy
The production of antibodies produced against tumor antigens that also recognize similar or identical molecules present on podocytes is a possible mechanism for malignancy-associated membranous nephropathy (MN). In a case report of a patient with anti-PLA2R-negative MN and concomitantly diagnosed adenoneuroendocrine carcinoma of the gallbladder, the expression of thrombospondin type-1 domain-containing 7A (THSD7A) was detected by immunohistochemistry on tumor cells but not on normal gallbladder tissue. The patient also had elevated plasma levels of anti-THSD7A antibodies, which the authors proposed were formed against abnormally expressed THSD7A by tumor cells. Treatment with chemotherapy led to the disappearance of THSD7A antibodies in the plasma within two weeks and a marked reduction in proteinuria. In a series of 24 other patients with MN and THSD7A antibodies, six were found to have a malignancy.