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PURPOSE The long-term toxicities of chemotherapy and radiotherapy can represent a significant burden to testicular cancer survivors. Retroperitoneal lymph node dissection (RPLND) is an established treatment for testicular germ cell tumors with minimal late morbidity although little data exist on its efficacy in early metastatic seminoma. Surgery in early metastatic seminoma is a prospective phase II single-arm, multi-institutional trial of RPLND as first-line treatment for testicular seminoma with clinically low-volume retroperitoneal lymphadenopathy. PATIENTS AND METHODS Twelve sites in the United States and Canada prospectively enrolled adult patients with testicular seminoma and isolated retroperitoneal lymphadenopathy (1-3 cm). Open RPLND was performed by certified surgeons with a primary end point of 2-year recurrence-free survival (RFS). Complication rates, pathologic up/downstaging, recurrence patterns, adjuvant therapies, and treatment-free survival were assessed. RESULTS A total of 55 patients were enrolled, with a median (IQR) largest clinical lymph node size of 1.6 cm (1.3-1.9). RPLND pathology demonstrated a median (IQR) largest lymph node size of 2.3 cm (0.9-3.5); nine patients (16%) were pN0, 12 (22%) pN1, 31 (56%) pN2, and 3 (5%) pN3. One patient received adjuvant chemotherapy. With a median (IQR) follow-up of 33 months (12.0-61.6), 12 patients experienced recurrence, with a 2-year RFS of 81% and a recurrence rate of 22%. Of the patients who experienced recurrence, 10 were treated with chemotherapy and two underwent additional surgery. At last follow-up, all patients who experienced a recurrence were disease-free and the 2-year overall survival was 100%. Four patients (7%) experienced short-term complications, and four patients experienced long-term complications including incisional hernia (1) and anejaculation (3). CONCLUSION RPLND is a treatment option for testicular seminoma with clinically low-volume retroperitoneal lymphadenopathy and is associated with low long-term morbidity.

PURPOSE Cisplatin is widely used and highly ototoxic, but patient-reported functional impairment because of cisplatin-related hearing loss (HL) and tinnitus has not been comprehensively evaluated. PATIENTS AND METHODS Testicular cancer survivors (TCS) given first-line cisplatin-based chemotherapy completed validated questionnaires, including the Hearing Handicap Inventory for Adults (HHIA) and Tinnitus Primary Function Questionnaire (TPFQ), each of which quantifies toxicity-specific functional impairment. Spearman correlations evaluated associations between HL and tinnitus severity and level of functional handicap quantified with the HHIA and TPFQ, respectively. Associations between HL or tinnitus and five prespecified adverse health outcomes (cognitive dysfunction, fatigue, depression, anxiety, and overall health) were evaluated. RESULTS HL and tinnitus affected 137 (56.4%) and 147 (60.5%) of 243 TCS, respectively. Hearing aids were used by 10% TCS (14/137). Of TCS with HL, 35.8% reported clinically significant functional impairment. Severe HHIA-assessed functional impairment was associated with cognitive dysfunction (odds ratio [OR], 10.62; P < .001), fatigue (OR, 5.48; P = .003), and worse overall health (OR, 0.19; P = .012). Significant relationships existed between HL severity and HHIA score, and tinnitus severity and TPFQ score ( P < .0001 each). TCS with either greater hearing difficulty or more severe tinnitus were more likely to report cognitive dysfunction (OR, 5.52; P = .002; and OR, 2.56; P = .05), fatigue (OR, 6.18; P < .001; and OR, 4.04; P < .001), depression (OR, 3.93; P < .01; and OR, 3.83; P < .01), and lower overall health (OR, 0.39; P = .03; and OR, 0.46; P = .02, respectively). CONCLUSION One in three TCS with HL report clinically significant functional impairment. Follow-up of cisplatin-treated survivors should include routine assessment for HL and tinnitus. Use of the HHIA and TPFQ permit risk stratification and referral to audiologists as needed, since HL adversely affects functional status and is the single largest modifiable risk factor for cognitive decline and dementia in the general population.

Without intervention, 80% of hips with osteonecrosis (ON) will progress. Core decompression (CD) has shown favorable results (60–80% survivorship) in early stage ON, and recently, bone marrow aspirate concentration (BMAC) injection into the decompressed femoral head has been proposed to stimulate healing of the necrotic lesion and improve outcomes and survivorship. We reviewed the clinical and radiographic outcomes of 51 Steinberg stage 2 hips in 31 patients who underwent CD + BMAC for ON with a minimum of 1 year follow-up. We evaluated preoperative visual analog pain scores (VAS), Steinberg stage based on radiographs, and Kerboul angle as measured on magnetic resonance imaging. Clinical outcomes were reported as a change in VAS at final follow-up, hip and disability osteoarthritis score for joint replacements (HOOS, JR) score at final follow-up, advancement in Steinberg stage based on radiographs, or decision to proceed with total hip arthroplasty (THA). At an average of 27 months, VAS scores improved from 7 to 2.3 (p

PURPOSE Ototoxicity is a prominent side effect of cisplatin-based chemotherapy. There are few reports, however, estimating its prevalence in well-defined cohorts and associated risk-factors. METHODS Testicular cancer (TC) survivors given first-line cisplatin-based chemotherapy completed validated questionnaires. Descriptive statistics evaluated ototoxicity prevalence. We compared patients with and without tinnitus or hearing loss using Chi-square test, two-sided Fisher's Exact test, or two-sided Wilcoxon Rank Sum test. To evaluate ototoxicity risk factors, a backward selection logistic regression procedure was performed. RESULTS Of 145 TC survivors, 74% reported ototoxicity: 68%-tinnitus; 59% hearing loss; and 52% reported both. TC survivors with tinnitus were more likely to indicate hypercholesterolemia (P=0.008), and difficulty hearing (PCONCLUSIONS Ototoxicity risk factors included age, cisplatin dose, cardiovascular risk factors, and family-history of hearing loss. Three of four TC survivors report some type of ototoxicity; thus, follow-up of cisplatin-treated survivors should include routine assessment for ototoxicity with provision of indicated treatments. IMPLICATIONS FOR CANCER SURVIVORS Survivors should be aware of risk factors associated with ototoxicity. Referrals to audiologists before, during, and after cisplatin treatment is recommended.

A tanulmány egy kutatás eredményeit foglalja össze, amely 18 idegennyelv-tanítással foglalkozó egyetemi szervezet vezetőjével folytatott interjúra épült. A hallgatók hozzáférése a nyelvtanításhoz a legtöbb intézményben jó. A nyelvtanítási célok tekintetében az egyetemi elvárások a döntőek: több intézményben a fő cél a szükséges nyelvvizsgák megszerzése, másutt a bekerülő nyelvtanulók már a felvételi előtt megszerezték ezeket. A felsőoktatáson belül a nyelvtanítás célja a szaknyelvoktatás, ezt azonban az érintettek különbözően értelmezik. Több intézményben a szaknyelvoktatást komplexen értelmezik, a munkához kapcsolódó nyelvhasználati területek elemzéséhez kapcsolódó kutatásokat is folytatnak, más intézmények inkább nyelviskolának tekintik magukat és/vagy a nyelvvizsga-felkészítésre fókuszálnak. Az intézmények fő jellemzője, hogy próbálnak igazodni a változó környezethez, mindenütt erős törekvés figyelhető meg a hagyományoktól való elszakadásra, ez azonban különböző mértékben történt meg.

Adjuvant therapy; Breast cancer; Olaparib Terapia adyuvante; Cáncer de mama; Olaparib Teràpia adjuvant; Càncer de mama; Olaparib Background The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. Patients and methods One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. Results With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Δ 3.4%, 95% CI −0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. Conclusion With 3.5 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDFS and DDFS with no new safety signals. Funding for this work, which was conducted as a collaborative partnership among the Breast International Group, NRG Oncology, Frontier Science, AstraZeneca, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, U.S.A. (MSD), was provided by the National Institutes of Health (grant numbers: U10CA 180868, UG1CA 189867, and U10CA 180822) and by AstraZeneca as part of an alliance between AstraZeneca and MSD. Provision of olaparib and placebo was from AstraZeneca.

Many advanced cancer patients struggle with anxiety, depressive symptoms, and anger toward God and illness-related stressors. Patients may perceive their illness as an injustice (i.e., appraise their illness as unfair, severe, and irreparable or blame others for their illness), which may be a risk factor for poor psychological and spiritual outcomes. This study examined relations between cancer-related perceived injustice and psycho-spiritual outcomes as well as potential mediators of these relationships.Advanced lung (n = 102) and prostate (n = 99) cancer patients completed a one-time survey. Using path analyses, we examined a parallel mediation model including the direct effects of perceived injustice on psycho-spiritual outcomes (i.e., anxiety, depressive symptoms, anger about cancer, anger towards God) and the indirect effects of perceived injustice on psycho-spiritual outcomes through two parallel mediators: meaning making and acceptance of cancer. We then explored whether these relations differed by cancer type.Path analyses indicated that perceived injustice was directly and indirectly-through acceptance of cancer but not meaning making-associated with psycho-spiritual outcomes. Results did not differ between lung and prostate cancer patients.Advanced cancer patients with greater perceived injustice are at higher risk for poor psycho-spiritual outcomes. Acceptance of cancer, but not meaning making, explained relationships between cancer-related perceived injustice and psycho-spiritual outcomes. Findings support testing acceptance-based interventions to address perceived injustice in advanced cancer patients.

PURPOSE According to National Comprehensive Cancer Network guidelines, adjuvant chemotherapy (AC) has been advocated after primary retroperitoneal lymph node dissection (RPLND) to reduce the risk of relapse in pathologic nodal (pN) stage pN2 or pN3, whereas surveillance is preferred for pN1. We sought to explore the oncologic efficacy of primary RPLND alone for pathologic stage II in nonseminomatous germ cell tumors (NSGCTs) to reduce overtreatment with chemotherapy. METHODS Patients with pathologic stage II NSGCT after primary RPLND between 2007 and 2017 were identified. Patients were excluded for elevated preoperative serum tumor markers, receipt of AC, or if pure teratoma or primitive neuroectodermal tumor elements were found in the retroperitoneal pathology. RESULTS We identified 117 patients with active NSGCT in the retroperitoneum after primary RPLND. We excluded seven patients who lacked meaningful follow-up and 13 patients who received AC. There were 97 patients treated with RPLND alone: 41 pN1, 46 pN2, and 10 pN3. In total, 77 of 97 patients had not recurred after a median follow-up time of 52 months. The 2-year recurrence-free survival (RFS) was 80.3%, and the 5-year RFS was 79%. No differences in RFS were noted among nodal stage—pN1, pN2, and pN3—on Kaplan-Meier analysis. Lymphovascular invasion in the orchiectomy specimen, a high-risk pathologic feature, was also predictive of recurrence after primary RPLND. All 20 patients who recurred were treated with first-line chemotherapy and remained continuously disease free. CONCLUSION Most men with pathologic stage II disease treated with surgery alone in our series never experienced a recurrence. We did not observe a difference in recurrences between patients with pN1 and pN2. The recommendation for AC for pN2 disease may be overtreatment in most patients.

What influences Taiwanese public opinion on immigration? Taiwan faces the same immigration challenges as many other developed nations, where the demand for immigrant workers produces a domestic backlash. Our study addresses to what extent public opinions on immigration are influenced by two factors: the skills of immigrants and their place of origin. Our results show, besides the preference for skilled labour, that public opinion on the three Southeast Asian immigrant groups varies considerably, with the strongest negative reaction to Indonesian migrants. As Taiwan prides its progress on human rights among East Asian democracies, the results suggest the need for targeted policy efforts to overcome public biases towards Southeast Asian immigrants.

Pregnant women diagnosed with CIN3 have high regression rates after delivery. Biomarkers are needed to only identify pregnant women with progressive CIN requiring treatment to reduce overreferral and overtreatment. In our study we evaluated the performance of the FAM19A4/miR124-2 methylation test for molecular triage on FFPE samples of CIN3+-diagnosed pregnant women with known clinical course over time as well in a cross-sectional setting. In this German multicenter retrospective study biopsy material was collected from pregnant women diagnosed with cervical cancer (n = 16), with CIN3 that progressed to cancer during pregnancy (n = 7), with CIN3 that regressed to CIN1 or less within 6 months after delivery (n = 41), without CIN (n = 16), CIN3 covering 3-4 quadrants (n = 14) and randomly selected CIN3 (n = 41). FAM19A4/miR124-2 methylation analysis was performed blinded on first diagnosis. All pregnant women with cervical cancer and with CIN3 progressing to cancer tested positive for FAM19A4/miR124-2 methylation (100%, 22/22). In the regressing CIN3 group 47.5% and in the group without CIN 21.6% tested methylation positive. High-volume CIN3 and random selected CIN3 were methylation-positive in 91.7% and 82.1%, respectively. Methylation levels were significantly higher in progressive CIN3 and cancer compared to the controls (P

Introduction Data science methodologies can be utilized to ascertain and analyze clinical genetic data that is often unstructured and rarely used outside of patient encounters. Methods Genetic variants from all genetic testing resulting to a large pediatric healthcare system for a five-year period were obtained and variants were reinterpreted utilizing the Franklin© Artificial Intelligence (AI). Utilizing PowerBI©, the data were further matched to patients in the electronic healthcare record and matched to demographic data to generate a variant data table and map variants as a choropleth. Results Three thousand sixty-five variants were identified and 98% were matched to patients with geographic data. Franklin© changed the interpretation for 27% of variants. A total of 723 Mendelian genetic disorders were identified with disorder prevalence estimation. Mapping of variants demonstrated hot-spots for pathogenic genetic variation such as PEX6-associated Zellweger Spectrum Disorder. Seven patients were identified with Bardet-Biedl syndrome and seven patients with Rett syndrome amenable to newly FDA-approved therapeutics. Discussion Utilizing readily available software we developed a database and Exploratory Data Analysis methodology enabling us to systematically reinterpret variants, estimate variant prevalence, identify patients amenable to new treatments, and localize geographies enriched for pathogenic variants.

Purpose:Cisplatin is a first-line chemotherapeutic for many cancers, but causes neurotoxicity including hearing loss, tinnitus, and peripheral sensory neuropathy. However, no study has comprehensively characterized risk factors for developing multiple (>1) severe neurotoxicities.Experimental Design:The relationship between multiple severe neurotoxicities and age, cumulative cisplatin dose, medical history, and lifestyle/behavioral factors was evaluated in 300 cisplatin-treated testicular cancer survivors using logistic regression. Case–control genome-wide association study (GWAS; cases, n = 104 and controls, n = 196) was also performed.Results:Age at clinical examination (P = 6.4 × 10−16) and cumulative cisplatin dose (P = 5.4 × 10−4) were positively associated with multiple severe neurotoxicity risk, as were high serum platinum levels (P = 0.02), tobacco use (ever smoker, P = 0.001 and current smoker, P = 0.002), and hypertension (P = 0.01) after adjustment for age and cumulative cisplatin dose. Individuals with multiple severe neurotoxicities were more likely to experience dizziness/vertigo (P = 0.01), Raynaud phenomenon (P = 3.7 × 10−9), and symptoms consistent with peripheral motor neuropathy (P = 4.3 × 10−14) after age and dose adjustment. These patients also reported poorer overall health (P = 2.7 × 10−5) and a greater use of psychotropic medications (P = 0.06). GWAS identified no genome-wide significant SNPs. Gene-based association analysis identified RGS17 (P = 3.9 × 10−5) and FAM20C (P = 5.5 × 10−5) as near genome-wide significant. Decreased FAM20C expression was associated with increased cisplatin sensitivity in tumor cell lines.Conclusions:Certain survivors are more susceptible to cisplatin-induced neurotoxicity, markedly increasing likelihood of developing numerous neuro-otological symptoms that affect quality of life. Genome-wide analysis identified genetic variation in FAM20C as a potentially important risk factor.

The Platinum Study CAO GWAS results for SNPs previously implicated in cisplatin-associated hearing loss.

Supplementary data from Clinical and Genome-wide Analysis of Cisplatin-induced Tinnitus Implicates Novel Ototoxic Mechanisms

Demographic features and clinical characteristics of 511 genetically European male germ cell tumor (GCT) survivors at the time of audiometry.

The design of the study, GWAS results, clinical characteristics are included in the supplemental data.

Robustness of the enrichment of top GWAS SNPs in Mendelian deafness genes.

Top SNPs (P < 1 x 10-5) in the meta-analysis of The Platinum Study and St. Jude cohorts.

Purpose:Cisplatin, a commonly used chemotherapeutic, results in tinnitus, the phantom perception of sound. Our purpose was to identify the clinical and genetic determinants of tinnitus among testicular cancer survivors (TCS) following cisplatin-based chemotherapy.Experimental Design:TCS (n = 762) were dichotomized to cases (moderate/severe tinnitus; n = 154) and controls (none; n = 608). Logistic regression was used to evaluate associations with comorbidities and SNP dosages in genome-wide association study (GWAS) following quality control and imputation (covariates: age, noise exposure, cisplatin dose, genetic principal components). Pathway over-representation tests and functional studies in mouse auditory cells were performed.Results:Cisplatin-induced tinnitus (CisIT) significantly associated with age at diagnosis (P = 0.007) and cumulative cisplatin dose (P = 0.007). CisIT prevalence was not significantly greater in 400 mg/m2-treated TCS compared with 300 (P = 0.41), but doses >400 mg/m2 (median 580, range 402–828) increased risk by 2.61-fold (P < 0.0001). CisIT cases had worse hearing at each frequency (0.25–12 kHz, P < 0.0001), and reported more vertigo (OR = 6.47; P < 0.0001) and problems hearing in a crowd (OR = 8.22; P < 0.0001) than controls. Cases reported poorer health (P < 0.0001) and greater psychotropic medication use (OR = 2.4; P = 0.003). GWAS suggested a variant near OTOS (rs7606353, P = 2 × 10−6) and OTOS eQTLs were significantly enriched independently of that SNP (P = 0.018). OTOS overexpression in HEI-OC1, a mouse auditory cell line, resulted in resistance to cisplatin-induced cytotoxicity. Pathway analysis implicated potassium ion transport (q = 0.007).Conclusions:CisIT associated with several neuro-otological symptoms, increased use of psychotropic medication, and poorer health. OTOS, expressed in the cochlear lateral wall, was implicated as protective. Future studies should investigate otoprotective targets in supporting cochlear cells.

Study design for subject and genotype quality control.

Purpose:Serum platinum is measurable for years after completion of cisplatin-based chemotherapy (CBC). We report the largest investigation of serum platinum levels to date of 1,010 testicular cancer survivors (TCS) assessed 1–35 years after CBC and evaluate genetic contributions to these levels.Experimental Design:Eligible TCS given 300 or 400 (±15) mg/m2 cisplatin underwent extensive audiometric testing, clinical examination, completed questionnaires, and had crude serum platinum levels measured. Associations between serum platinum and various risk factors and toxicities were assessed after fitting a biexponential model adjusted for follow-up time and cumulative cisplatin dose. A genome-wide association study (GWAS) was performed using the serum platinum residuals of the dose and time-adjusted model.Results:Serum platinum levels exceeded the reference range for approximately 31 years, with a strong inverse relationship with creatinine clearance at follow-up (age-adjusted P = 2.13 × 10−3). We observed a significant, positive association between residual platinum values and luteinizing hormone (age-adjusted P = 6.58 × 10−3). Patients with high residual platinum levels experienced greater Raynaud phenomenon than those with medium or low levels (age-adjusted ORhigh/low = 1.46; P = 0.04), as well as a higher likelihood of developing tinnitus (age-adjusted ORhigh/low = 1.68, P = 0.07). GWAS identified one single-nucleotide polymorphism (SNP) meeting genome-wide significance, rs1377817 (P = 4.6 × 10−8, a SNP intronic to MYH14).Conclusions:This study indicates that residual platinum values are correlated with several cisplatin-related toxicities. One genetic variant is associated with these levels.

Purpose: Cisplatin is one of the most commonly used chemotherapy drugs worldwide and one of the most ototoxic. We sought to identify genetic variants that modulate cisplatin-associated ototoxicity (CAO).Experimental Design: We performed a genome-wide association study (GWAS) of CAO using quantitative audiometry (4–12 kHz) in 511 testicular cancer survivors of European genetic ancestry. We performed polygenic modeling and functional analyses using a variety of publicly available databases. We used an electronic health record cohort to replicate our top mechanistic finding.Results: One SNP, rs62283056, in the first intron of Mendelian deafness gene WFS1 (wolframin ER transmembrane glycoprotein) and an expression quantitative trait locus (eQTL) for WFS1 met genome-wide significance for association with CAO (P = 1.4 × 10−8). A significant interaction between cumulative cisplatin dose and rs62283056 genotype was evident, indicating that higher cisplatin doses exacerbate hearing loss in patients with the minor allele (P = 0.035). The association between decreased WFS1 expression and hearing loss was replicated in an independent BioVU cohort (n = 18,620 patients, Bonferroni adjusted P < 0.05). Beyond this top signal, we show CAO is a polygenic trait and that SNPs in and near 84 known Mendelian deafness genes are significantly enriched for low P values in the GWAS (P = 0.048).Conclusions: We show for the first time the role of WFS1 in CAO and document a statistically significant interaction between increasing cumulative cisplatin dose and rs62283056 genotype. Our clinical translational results demonstrate that pretherapy patient genotyping to minimize ototoxicity could be useful when deciding between cisplatin-based chemotherapy regimens of comparable efficacy with different cumulative doses. Clin Cancer Res; 23(13); 3325–33. ©2016 AACR.

Proportion of variance in WFS1 expression explained by genetic effects in 11 relevant GTEx tissues.

Purpose: Our purpose was to characterize the clinical influences, genetic risk factors, and gene mechanisms contributing to persistent cisplatin-induced peripheral neuropathy (CisIPN) in testicular cancer survivors (TCSs).Experimental Design: TCS given cisplatin-based therapy completed the validated EORTC QLQ-CIPN20 questionnaire. An ordinal CisIPN phenotype was derived, and associations with age, smoking, excess drinking, hypertension, body mass index, diabetes, hypercholesterolemia, cumulative cisplatin dose, and self-reported health were examined for 680 TCS. Genotyping was performed on the Illumina HumanOmniExpressExome chip. Following quality control and imputation, 5.1 million SNPs in 680 genetically European TCS formed the input set. GWAS and PrediXcan were used to identify genetic variation and genetically determined gene expression traits, respectively, contributing to CisIPN. We evaluated two independent datasets for replication: Vanderbilt's electronic health database (BioVU) and the CALGB 90401 trial.Results: Eight sensory items formed a subscale with good internal consistency (Cronbach α = 0.88). Variables significantly associated with CisIPN included age at diagnosis (OR per year, 1.06; P = 2 × 10−9), smoking (OR, 1.54; P = 0.004), excess drinking (OR, 1.83; P = 0.007), and hypertension (OR, 1.61; P = 0.03). CisIPN was correlated with lower self-reported health (OR, 0.56; P = 2.6 × 10−9) and weight gain adjusted for years since treatment (OR per Δkg/m2, 1.05; P = 0.004). PrediXcan identified lower expressions of MIDN and RPRD1B, and higher THEM5 expression as associated with CisIPN (P value for each < 5 × 10−6) with replication of RPRD1B meeting significance criteria (Fisher combined P = 0.0089).Conclusions: CisIPN is associated with age, modifiable risk factors, and genetically determined expression level of RPRD1B. Further study of implicated genes could elucidate the pathophysiologic underpinnings of CisIPN. Clin Cancer Res; 23(19); 5757–68. ©2017 AACR.

The Platinum Study CAO GWAS results for SNPs in Mendelian deafness genes.

Top GWAS SNP rs62283056 is a cis-acting eQTL for WFS1 in several tissues.

Supplementary Figures and Tables for Clinical and Genome Wide Analysis of Cisplatin-Induced Peripheral Neuropathy in Survivors of Adult-Onset Cancer Figure S1. Diagram of Data Collection Pipeline. Table S1. EORTC-CIPN20 questionnaire. Figure S2. Flow diagram of GWAS Quality Control Pipeline. Table S2. Additional Diagnosis and Treatment Characteristics of TCS cohort. Figure S3. Response frequencies for the EORTC-CIPN20 questionnaire from 680 patients. Figure S4. Principal Component Analysis (PCA) of EORTC-CIPN20 items. Figure S5. SNP-level GWAS. Table S3. Top 100 GWAS Results (p < 2.25 x 10-5) Table S4. Review of candidate gene studies implicating SNPs in cisplatin-induced neuropathy and their replication in the TCS study. Table S5. Review of previous GWAS of CIPN implicating SNPs and their replication in the TCS study. Table S6. Top PrediXcan results (P < 0.001).

PURPOSE The majority of patients with advanced nonseminomatous germ-cell tumor are cured with combination chemotherapy and surgical resection of residual disease when appropriate. In patients with both retroperitoneal (RP) and non-RP postchemotherapy residual disease, management of the non-RP disease is typically guided by pathologic findings at the time of RP resection. There are limited data to help guide management decisions in patients with non-RP postchemotherapy residual disease alone. MATERIALS AND METHODS The prospectively maintained Indiana University testicular cancer database was queried for patients with metastatic nonseminomatous germ-cell tumor treated between 1990 and 2021 who had residual non-RP disease in the absence of residual RP disease after completing either first-line or salvage chemotherapy. RESULTS One hundred twenty-nine patients met eligibility and were included in this analysis. Seventy-five patients had teratoma in the primary tumor site, while 54 did not. Of those with teratoma in the primary, 55% had at least one postchemotherapy non-RP surgical specimen with teratomatous elements compared with 17% of those without teratoma in the primary ( P < .001). Of those without teratoma in the primary site, 56% had at least one postchemotherapy non-RP surgical specimen with active germ-cell tumor compared with 31% of those with teratoma in the primary ( P = .0046). CONCLUSION The presence of teratoma in the primary tumor site is associated with a higher rate of teratoma in postchemotherapy residual non-RP disease. Patients without teratoma in the primary tumor should still be considered for resection of residual postchemotherapy disease that could harbor teratoma or active germ-cell tumor.

PURPOSE On the basis of National Comprehensive Cancer Network guidelines, clinical stage (CS) II seminoma is treated with radiotherapy or chemotherapy. Primary retroperitoneal lymph node dissection (RPLND) demonstrated recent success as first-line therapy for RP-only disease. Our aim was to confirm surgical efficacy and evaluate recurrences after primary RPLND for CS IIA/IIB seminoma to determine if various clinical factors could predict recurrences. PATIENTS AND METHODS Patients who underwent primary RPLND for seminoma from 2014 to 2021 were identified. All patients had at least 6 months of follow-up. Nineteen patients were part of a clinical trial. Patients receiving adjuvant chemotherapy were excluded from Kaplan-Meier recurrence-free survival (RFS) analysis. RESULTS We identified 67 patients who underwent RPLND for RP-only seminoma. One patient had pN0 disease. Median follow-up time after RPLND was 22.4 months (interquartile range, 12.3-36.1 months) and 11 patients were found to have a recurrence. The 2-year RFS for RPLND-only patients without adjuvant chemotherapy was 80.2%. Patients who developed RP disease for a period > 12 months had the lowest chance of recurrence, with a 2-year RFS of 92.2%. Seven initial CS II patients were on surveillance for 3-12 months before surgery and no patients experienced recurrence. Pathologic nodal stage and high-risk factors such as tumor size > 4 cm or rete testis invasion of the orchiectomy specimen did not affect recurrence. CONCLUSION CS II seminoma can be treated with surgery to avoid rigors of chemotherapy or radiotherapy. Patients with delayed development of CS II disease (> 12 months) had the best surgical results. Patients may present with borderline CS II disease, and careful surveillance may avoid overtreatment. Further study on patient selection and extent of dissection remains uncertain and warrants further investigation.

Closed reduction and percutaneous internal fixation (CRPIF) for acetabular fractures was introduced as a less invasive alternative to open reduction and internal fixation (ORIF) for moderately displaced fractures. Currently, comparisons of ORIF and CRPIF outcomes are rare. Twenty-three patients treated with CRPIF were matched with patients treated with ORIF based on sex, age, and fracture classification. Surgery-dependent and -independent factors of the in-hospital stay, the conversion rate to total hip arthroplasty (THA), and quality of life were assessed. The ORIF group had a higher preoperative fracture step (p = 0.04) and gull wing sign (p = 0.003) compared with the CRPIF group. Postoperatively, the gap and step size were not significantly different between the groups (p > 0.05). CRPIF required less time (p < 0.0001) and transfusions (p = 0.009) and showed fewer complications (p = 0.0287). Four patients were converted to THA (CRPIF, n = 1; ORIF, n = 3; p = 0.155) because of posttraumatic osteoarthritis. Functional outcomes and pain were similar in both groups (p > 0.05). The present study revealed less blood loss and a lesser extent of reduction in patients treated with CRPIF than in those treated with ORIF. The rates of conversion to THA and functional outcomes did not differ between CRPIF and ORIF. CRPIF appeared to be a valuable treatment option for selected patients.