Bisphosphonates are widely used for various conditions, including osteoporosis, hypercalcemia of malignancy, osteolytic bone metastasis, and Paget's disease. Bisphosphonate-induced orbital inflammation is a rare side effect of amino-bisphosphonates. There has been less focus on the risk of developing amino-bisphosphonate-induced orbitopathy in people who have underlying ophthalmopathy. Herein, we present a case of alendronate-induced acute orbital inflammation in a patient with underlying Graves’ ophthalmopathy. Soon after administration of intravenous (IV) dexamethasone with topical prednisolone, the inflammation rapidly resolved. To our knowledge, this is the first case of bisphosphonate-induced orbital inflammation with underlying orbitopathy. This case demonstrates that systemic corticosteroids can be an effective treatment in orbital inflammation in similar cases. There is a possible interaction of T-cell and cytokine involvement mechanisms between Graves’ orbitopathy and bisphosphonate-induced orbital inflammation. This case also shows that bisphosphonate-induced acute orbital inflammation is rare but should be part of a physician's differential diagnosis, and more precautions are necessary for patients with underlying orbitopathy who are taking bisphosphonates.
Introduction: Alterations in DNA damage repair (DDR) genes are observed in up to 60% of biliary tract cancer (BTC) patients. Patients with advanced/metastatic BTC have few therapeutic options, so there is a demand for the development of new and innovative treatment approaches. The use of poly-adenosine diphosphate-ribose polymerase (PARP) inhibitors (PARPis), either as a monotherapy or in combination, is being extensively studied in clinical trials.Areas Covered: This review examines the targeting of the DDR pathway with PARPis as a potential novel treatment option for the management of BTCs. The rationale behind the use of PARPis and current clinical experience is discussed. Moreover, further insights into potential future directions concerning the applicability of PARPis in the treatment of BTCs are proposed.Expert Opinion: Prospective clinical data with PARPis in the treatment of BTCs are limited. The potential combination of PARPis and IDH1 inhibitors or immune checkpoint inhibitors in clinical trials is interesting because of the potential synergistic preclinical data. There are other possible combinations including those drugs that target the angiogenesis or STAT3 pathways. An enhanced understanding of acquired resistance to PARPis is necessary to progress the use of these agents in clinical trials.
With the development of immune checkpoint inhibitors, immunotherapy researchers have facilitated substantial progress for patients with mismatch repair deficient/microsatellite instability-high colorectal cancer, which has led to practice changes at a head-spinning pace. However, this benefit has not been translated into microsatellite stable colorectal cancer, which carries the hallmarks of chromosomal instability. So far, clinical trials have not shown any substantial clinical benefits of immune checkpoint inhibitor therapy for patients with microsatellite stable colorectal cancer, which has been disappointing. Recently, combinations of immune checkpoint inhibitors with tyrosine kinase inhibitors and targeted therapies have been investigated for potential synergistic effects that may increase antitumor activity in the tumor microenvironment and achieve more substantial clinical and radiologic responses. In this article, we discuss the current state of the science for the use of immune checkpoint inhibitors in microsatellite stable colorectal cancers, and we review the molecular underpinnings of inherited physiologic barriers for the delivery of effective immunotherapy. We also elaborate on existing therapeutic opportunities to convert microsatellite stable colorectal cancer into an "immune hot" cancer, which may define the future treatment paradigm of colorectal cancer for which there is a great unmet need.
Abstract Purpose Hypofractionated whole breast radiation therapy (hypofractionation) for early-stage breast cancer is a treatment innovation that is both supported by high quality randomized trial evidence and clinical guidelines, and is more cost effective and convenient than conventional fractionation. However, whether hypofractionation has been adopted nationally, and what factors are related to its adoption, are unknown. Methods We performed a retrospective study of breast cancer patients in the National Cancer Data Base from 2004-2011 who were treated with radiation therapy and met eligibility criteria for hypofractionation. We used logistic regression to identify factors associated with receipt of hypofractionation (vs. conventional fractionation). Results We identified 13,271 (11.7%) and 99,996 (88.3%) women with early-stage breast cancer who were treated with hypofractionation and conventional fractionation, respectively. The use of hypofractionation increased significantly, with 5.4% of patients receiving it in 2004 compared with 22.8% in 2011 (P<0.001 for trend). Patients living >50 miles from the cancer reporting facility had increased odds of receiving hypofractionation (OR 1.57 [95% CI 1.44-1.72], p<.001). Adoption of hypofractionation was associated with treatment at an academic center (p<0.001) and living in an area with high median income (p<0.001). Hypofractionation was less likely to be used in patients with high risk disease, such as increased tumor size (p<0.001) or poorly differentiated histologic grade (p<0.001). Adjusted odds ratios for receipt of conventional fractionation vs hypofractionationFeature (Reference)OR (95% CI)p-valueFacility Type (Academic)Community0.38 (0.35-0.42)<0.001Comprehensive Community0.51 (0.48-0.53)<0.001Other0.64 (0.52-0.78)<0.001Facility Location (South)Northeast0.93 (0.88-0.99)0.02Midwest1.04 (1.00-1.11)0.07West1.69 (1.59-1.78)<0.001Age in yrs (50-59)60-691.22 (1.16-1.29)<0.00170-791.77 (1.66-1.89)<0.001>=803.12 (2.88-3.38)<0.001Race (White)Black0.96 (0.89-1.05)0.41White Hispanic1.23 (1.10-1.36)<0.001Other1.23 (1.13-1.34)<0.001Primary Payor (Private insurance)No insurance1.16 (0.96-1.41)0.11Medicaid0.97 (0.86-1.10)0.71Medicare1.05 (1.00-1.11)0.05Other government0.81 (0.63-1.05)0.12Unknown1.22 (1.03-1.44)0.02Median Income Quartile (<$30 000)30 000 - 35 0000.95 (0.87-1.04)0.3035 000 - 45 9990.97 (0.90-1.06)0.54>= 46 0001.25 (1.16-1.35)<0.001Unknown1.04 (0.86-1.25)0.70Urbanization (Metro)Urban0.88 (0.83-0.95)0.001Rural1.10 (0.99-1.22)0.07Distance from reporting facility (<50 miles)>=50 miles1.57 (1.44-1.72)<0.001Unknown1.13 (0.91-1.40)0.27Year of Diagnosis (2004)20051.03 (0.92-1.14)0.6520061.11 (1.00-1.24)0.0520071.31 (1.18-1.45)<0.00120081.99 (1.80-2.19)<0.00120092,88 (2.62-3.15)<0.00120104.10 (3.62-4.64)<0.00120115.48 (4.83-6.21)<0.001Grade (Well-differentiated)Intermediate0.94 (0.89-0.97)<0.01Poor0.86 (0.80-0.91)<0.001Undifferentiated1.03 (0.5-1.63)0.89Unknown0.90 (0.82-0.99)0.04Tumor Size (<10 mm)10-29 mm0.90 (0.87-0.94)<0.00130-49 mm0.71 (0.62-0.80)<0.001>=50 mm0.94 (0.67-1.32)0.76Unknown0.63 (0.42-0.95)0.03 Conclusions The use of hypofractionation is rising and is associated with increased travel distance and treatment at an academic center. Further adoption of hypofractionation may be tempered by both clinical and non-clinical concerns. Citation Format: Elyn H Wang, Sarah S Mougalian, Pamela R Soulos, Charles E Rutter, Suzanne B Evans, Bruce G Haffty, Cary P Gross, James B Yu. The adoption of hypofractionated whole breast irradiation for early-stage breast cancer: A national cancer data base analysis [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-15-04.
