Osteonecrosis of the Maxilla and Mandible in Patients with Advanced Cancer Treated with Bisphosphonate Therapy

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139939/1/onco0911.pd

p27 expression in post-treatment rectal cancer: a potential novel approach for predicting residual nodal disease

Expression profiles of p21, p27, p53, Ki-67, and thymidylate synthase may be associated with response to neoadjuvant chemoradiation. The relationship between post-treatment protein expression and regional lymph node involvement has not been fully explored. Tumor cores from 126 rectal cancer patients underwent immunohistochemical analysis for the aforementioned proteins. Staining indices (SIs) using percentage of stained cells and staining intensity were calculated for 10 tumor cores per patient. SI for each marker was compared between node negative and node positive patients. Twenty-six (20.6%) cancer patients had a pathologic complete response and 37 had inadequate tissue or cancer cells, leaving 63 for analysis. Thirty-seven (58.7%) cancer patients were node negative and 26 (41.3%) were node positive. There was an association between increased p27 SI and nodal positivity (P = .04). Increased p27 expression in post-treatment rectal cancer is associated with nodal positivity and may determine which patients are suitable for local excision

High Incidence of Thromboembolic Events in Patients Treated With Cisplatin-Based Chemotherapy: A Large Retrospective Analysis

Purpose This study was designed to determine the incidence of venous and arterial thromboembolic events (TEEs) in patients treated with cisplatin-based chemotherapy and to analyze the prognostic value of patients' baseline and treatment characteristics in predicting TEE occurrence. Patients and Methods We performed a large retrospective analysis of all patients treated with cisplatin-based chemotherapy for any type of malignancy at Memorial Sloan-Kettering Cancer Center in 2008. A TEE was cisplatin-associated if it occurred between the time of the first dose of cisplatin and 4 weeks after the last dose. Results Among 932 patients, 169 (18.1%) experienced a TEE during treatment or within 4 weeks of the last dose. TEEs included deep vein thrombosis (DVT) alone in 49.7%, pulmonary embolus (PE) alone in 25.4%, DVT plus PE in 13.6%, arterial TEE alone in 8.3%, or DVT plus arterial TEE in 3.0%. TEEs occurred within 100 days of initiation of treatment in 88% of patients. By univariate analysis, sex, age, race, Karnofsky performance status (KPS), exposure to erythropoiesis-stimulating agents, presence of central venous catheter (CVC), site of cancer, stage of cancer, leukocyte and hemoglobin levels, and Khorana score were all identified as risk factors. However, by multivariate analysis, only age, KPS, presence of CVC, and Khorana score retained significance. Conclusion This large retrospective analysis confirms the unacceptable incidence of TEEs in patients receiving cisplatin-based chemotherapy. In view of the controversy associated with prophylactic anticoagulation in patients with cancer treated with chemotherapy, randomized studies are urgently needed in this specific cancer population treated with cisplatin-based regimens

Adjuvant Bortezomib and Dexamethasone Following Risk-Adapted Melphalan and Stem Cell Transplant in Systemic Light-Chain Amyloidosis (AL): A Phase II Study

Abstract Abstract 533 Background: High-dose melphalan (MEL) and autologous stem cell transplant (SCT) induces hematologic and clinical remissions in AL and results in prolonged survival. In a prior phase II study we showed that post-SCT adjuvant thalidomide and dexamethasone improved hematologic responses in 42% of patients, resulting in a 39% strictly defined complete response (sCR) rate at 12 months (mos) post-SCT (BJH 2007;139:224). With a median follow-up of 52 mos, the overall survival of patients on that study is 69%. We now report on an ongoing phase II trial in which we use adjuvant bortezomib and dexamethasone (BD) following risk-adapted SCT. Methods: Patients with newly diagnosed AL involving ≤2 organs were assigned to MEL 100, 140 or 200mg/m2 with SCT, based on age, renal function and cardiac involvement. Responses were assessed at 2-3 mos, 12 mos and 24 mos post-SCT. Patients with persistent clonal plasma cell disease at 2-3 mos post-SCT received adjuvant BD for up to 6 cycles (two 21-day, four 35-day cycles). At 12 mos post-SCT we evaluated hematologic, organ responses and overall survival (OS). Results: Thirty patients have been enrolled with kidney (63%), heart (47%), liver/GI (10%) and peripheral nervous system (10%) involvement, including 38% with two organ-involvement. Three patients were removed from study prior to SCT due to three organ-involvement, co-morbid illness or the development of pulmonary edema while receiving filgrastim for stem cell mobilization; one patient is undergoing stem cell collection. SCT-related 100-day mortality was 12% (3/26), with all deaths occurring in patients with stage II or III cardiac amyloid. With a median follow-up of 20 mos, the one-year OS post-SCT is 83%. One-year OS in patients with cardiac involvement is 50% versus 100% in those without (P < 0.01). In 23 patients evaluable post-SCT, the overall response rate was 52% with 22% sCR. Seventy-four percent (17/23) received adjuvant BD for persistent clonal plasma cell disease. One patient (4%) was ineligible for adjuvant therapy due to thrombocytopenia that developed on immunosuppressive therapy following orthotopic heart transplant. At 12 mos post-SCT, the hematologic response rate in evaluable patients was 95% (18/19) with 74% (14/19) achieving sCR and 58% (11/19) having organ improvement. Ninety-three percent (13/14) of patients who received adjuvant BD and were evaluable at 12 mos post-SCT had improved hematologic responses. Overall, of the 17 patients who received adjuvant BD, 71% of patients experienced grade II-IV toxicity with thrombocytopenia (41%), ≥ grade 2 peripheral neuropathy (35%) and respiratory infection (16%) being most common and one patient with cardiac amyloid experiencing sudden death. Conclusions: In newly diagnosed patients with systemic AL amyloidosis, adjuvant BD following risk-adapted SCT is well-tolerated and effective for eradicating persistent clonal plasma cell disease. At 12 mos post-SCT high overall and unprecedented sCR rates are seen with frequent organ response, demonstrating that this strategy merits further study. Disclosures: Comenzo: Millenium: Consultancy, Membership on an entity's Board of Directors or advisory committees