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Background The aim of this study is to evaluate the current state of ototoxicity monitoring for patients receiving cisplatin chemotherapy in an academic medical center with particular attention to how closely monitoring adheres to national ototoxicity guidelines. Methods Case series including retrospective medical records review of patients (age > 18) treated with cisplatin at University of California Davis Medical Center between January 2014 and August 2017. Patient and ototoxicity related variables were analyzed. Patients that underwent a transfer of care during treatment and with less than 3 months of follow-up were excluded. Results Three hundred seventy-nine patients met study criteria, of which 104 (27.4%) had a prior history of hearing loss. Prior to treatment, 196 (51.7%) patients were counseled regarding the ototoxic nature of cisplatin and 92 (24.3%) patients had a pretreatment audiogram. During treatment, 91 (24%) patients had documented otologic complaints. Only 17 patients (4.5%) patients had an audiogram ordered during their cisplatin treatment period. 130 (34.3%) patients had otologic complaints following cisplatin treatment. Audiograms were ordered for 20 (7.8%), 13 (5.1%), and 16 (6.2%) patients at 1-month, 3-month, and 6-month follow-ups, respectively. No patients in the study cohort received baseline, treatment, and post-treatment audiograms as recommended by national ototoxicity monitoring protocols. Patients with Head and Neck Cancer (HNC) represented the largest subgroup that received cisplatin (n = 122, 32.2%) and demonstrated higher rates of ototoxicity counseling (n = 103, 84.4%) and pretreatment audiograms (n = 70, 57.4%) compared to the non HNC group (n = 36, 36.2%, P < 0.0001 and n = 22, 8.5%, P < 0.0001). Conclusions There is poor adherence to national ototoxicity monitoring guidelines at a large academic medical center. This is a missed opportunity for intervention and aural rehabilitation. Improved education and collaboration between otolaryngology, audiology, and medical oncology is needed to develop and promote an effective ototoxicity-monitoring program. Graphical abstract

Introduction Hematologic malignancies are a heterogeneous group of diseases characterized by the uncontrolled growth of malignant hematopoietic cells. Given this heterogeneity, it is likely that the etiology for these conditions is also diverse and distinct between them. Systemic lupus erythematosus (SLE) is a chronic inflammatory condition that has been associated with an increased risk of developing non-Hodgkin lymphoma (NHL). However, the role of SLE in the etiology of other hematologic malignancies is unclear. The primary objective of our study is to evaluate, using a meta-analysis of observational studies, the association between SLE and NHL, Hodgkin lymphoma (HL), leukemia and myeloma. A secondary objective was to evaluate potential differences according to geographical region. Methods At least two of the investigators performed a MEDLINE search from January 1, 1995 through June 30, 2013 looking for cohort studies reporting on the association between SLE and the risk of developing hematologic malignancies. The search keyword was “lupus AND (leukemia OR lymphoma OR myeloma)”. Data were gathered independently by at least two of the investigators and disagreements were addressed by consensus. The outcome of interest was the standardized incidence ratio (SIR) and 95% confidence interval (CI) of hematological malignancies in adult patients with SLE in comparison with the general population. The outcome was calculated using the random-effects model (REM), which adjusts for inter and intra-study heterogeneity. Additionally, heterogeneity was assessed using the I2 index. I2values of 25%, 50% and 75% indicated low, moderate and severe heterogeneity, respectively. The quality of the studies was assessed separately by at least two of the investigators using the Newcastle-Ottawa scale (NOS). Studies with NOS 1-3, 4-6 and 7-9 were considered of low, intermediate and high quality, respectively. Publication bias was assessed by the trim-and-fill analysis, which identifies and adjusts for imputed unpublished studies. Subset analyses were performed by geographical region (i.e. Asia, Europe and North America). All calculations and graphics obtained using Comprehensive Meta-Analysis version 2.2.050 (Biostat, New Jersey, USA). Results Our initial search found 976 studies, from which 15 studies were included in our analysis. Eight studies (53%) were from Europe, 4 (27%) from North America, 2 (13%) from Asia and 1 (7%) was a multi-national efforts. Cohort studies identified 488 cases of hematologic malignancies among 70,375 individuals (87% women, 13% men) with a diagnosis of SLE. Based on the NOS scale, 12 studies (80%) were considered of high and 3 (20%) of intermediate quality. SLE was associated with increased SIR of NHL (SIR 5.3, 95% CI 3.6-7.9, p<0.001) with high heterogeneity (I2=91%). The increased SIR of NHL was seen in all geographical regions: Europe SIR 6.4 (95% CI 2.9-13.8; p<0.001), North America SIR 4.6 (95% CI 2.6-8.3; p<0.001), Asia SIR 9.2 (95% CI 4.7-18.2; p<0.001). SLE was associated with a high SIR of HL (SIR 3.9, 95% CI 2.4-6.3; p<0.001) with moderate heterogeneity (I2=33%). The SIR of HL was increased in European (SIR 5.5, 95% CI 2.6-11.7; p<0.001) and North American studies (SIR 4.7, 95% CI 1.3-17.1; p=0.017). SLE was also associated with increased SIR of leukemia (SIR 2.3, 95% CI 1.8-2.9, p<0.001) with moderate heterogeneity (I2=49%). The SIR of leukemia was increased in all regions: Europe SIR 3.0 (1.1-7.6; p=0.026), North America SIR 2.2 (1.7-2.8; p<0.001), Asia SIR 2.6 (2.5-2.8; p<0.001). A weaker association was found between SLE and myeloma (SIR 1.5, 95% CI 1.0-2.0, p=0.03) without heterogeneity (I2=0%). Subset analysis by geographical region could not be undertaken in patients with myeloma. Publication bias would have not affected any of our results. Conclusions Compared with the general population, individuals with SLE have an increased SIR of hematologic malignancies. Not surprisingly, SLE was associated with a 5-fold increase in SIRs for NHL. However, SLE was also associated with increased SIR of HL (4-fold), leukemia (2-fold) and, at a lower degree, myeloma (1.5-fold). Our subset analysis showed that SLE increases the SIR of NHL, HL and leukemia regardless of the geographical region. Further studies are needed to elucidate the pathogenetic role of SLE in hematologic malignancies. Disclosures: No relevant conflicts of interest to declare.