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A 25-year-old Filipino woman living in the USA was evaluated for a 5-month history of left eye pain and a subsequent orbital mass. Histopathological analysis of the lacrimal mass showed a mixed inflammatory process with necrotising granulomas and positive cultures for Mycobacterium tuberculosis. She was treated with antituberculosis therapy, with resolution of symptoms. Tuberculosis dacryoadenitis is extremely rare in the USA and other developed countries. It requires a high degree of clinical suspicion with special attention to the patient’s history to make the correct diagnosis. It can be treated successfully with antituberculosis therapy.

Purpose The purpose of this study was to evaluate the noninferiority of Day 30 dosimetry between a machine learning–based treatment planning system for prostate low-dose-rate (LDR) brachytherapy and the conventional, manual planning technique. As a secondary objective, the impact of planning technique on clinical workflow efficiency was also evaluated. Materials and Methods 41 consecutive patients who underwent I-125 LDR monotherapy for low- and intermediate-risk prostate cancer were accrued into this single-institution study between 2017 and 2018. Patients were 1:1 randomized to receive treatment planning using a machine learning–based prostate implant planning algorithm (PIPA system) or conventional, manual technique. Treatment plan modifications by the radiation oncologist were evaluated by computing the Dice coefficient of the prostate V150% isodose volume between either the PIPA—or conventional—and final approved plans. Additional evaluations between groups evaluated the total planning time and dosimetric outcomes at preimplant and Day 30. Results 21 and 20 patients were treated using the PIPA and conventional techniques, respectively. No significant differences were observed in preimplant or Day 30 prostate D90%, V100%, rectum V100, or rectum D1cc between PIPA and conventional techniques. Although the PIPA group had a larger proportion of patients with plans requiring no modifications (Dice = 1.00), there was no significant difference between the magnitude of modifications between each arm. There was a large significant advantage in mean planning time for the PIPA arm (2.38 ± 0.96 min) compared with the conventional (43.13 ± 58.70 min) technique (p >> 0.05). Conclusions A machine learning–based planning workflow for prostate LDR brachytherapy has the potential to offer significant time savings and operational efficiencies, while producing noninferior postoperative dosimetry to that of expert, conventional treatment planners.

Purpose/objective To report biochemical control associated with single fraction 15 Gy high-dose-rate brachytherapy (HDR-BT) boost followed by external beam radiation (EBRT) in patients with intermediate-risk prostate cancer. Materials and methods A retrospective chart review of all patients with intermediate-risk disease treated with a real-time ultrasound-based 15 Gy HDR-BT boost followed by EBRT between 2009 and 2016 at a single quaternary cancer center was performed. Freedom from biochemical failure (FFBF), cumulative incidence of androgen deprivation therapy use for biochemical or clinical failure post-treatment (CI of ADT) and metastasis-free survival (MFS) outcomes were measured. Results 518 patients met the inclusion criteria for this study. Median age at HDR-BT was 67 years (IQR 61–72). 506 (98%) had complete pathologic information available. Of these, 146 (28%) had favorable (FIR) and 360 (69%) had unfavorable (UIR) intermediate-risk disease. 83 (16%) received short course hormones with EBRT + HDR. Median overall follow-up was 5.2 years. FFBF was 91 (88–94)% at 5 years. Five-year FFBF was 94 (89–99)% and 89 (85–94)% in FIR and UIR patients, respectively (p = 0.045). CI of ADT was 4 (2–6)% at 5 years. Five-year CI of ADT was 1 (0–3)% and 5 (2–8)% in FIR and UIR patients, respectively (p = 0.085). MFS was 97 (95–98)% at 5 years. Five-year MFS was 100 (N/A-100)% and 95 (92–98)% in FIR and UIR patients, respectively (p = 0.020). Conclusion In this large cohort of intermediate-risk prostate cancer patients, 15 Gy HDR-BT boost plus EBRT results in durable biochemical control and low rates of ADT use for biochemical failure.

Adhesion formation is a major problem when a mesh is exposed to intraabodminal viscera, with potential severe complications (bowel occlusion, fistulas or abscesses). New methods for preventing adhesions from a polypropylene mesh placed intra-abdominally or to solve difficult situations, such as when the peritoneum cannot be closed during a TAPP repair for an inguinal hernia, are still being seeked. This study mimics in an animal model a situation that can be found in clinical practice during laparoscopic inguinal hernioplasty. A polypropylene mesh could be exposed to the intra-abdominal cavity even when the peritoneum is closed due to different circumstances, with no options to guarantee the prosthetic material of being exposed to the intrabdominal viscera. Different options have been suggested to solve these situations, being proposed in this study to cover the visceral surface of the mesh with an absorbable sponge containing thrombin, fibrinogen, and clotting factors (TachosilThirty Wistar white rats (300-450 mg) were included in this study as experimental animals, being randomized into three groups (A, B, and C). We performed a bilateral prosthetic repair with conventional polypropylene mesh (2 × 2 cm, 82 kD). Prosthesis fixation was performed as follows. Group A: absorbable suture; group B: metal staples; group C: metal tackers. A piece of insulating absorbable sponge (TachosilTachosilThe use of Tachosil

[Background]: Adhesion formation is a major problem when a mesh is exposed to intraabodminal viscera, with potential severe complications (bowel occlusion, fistulas or abscesses). New methods for preventing adhesions from a polypropylene mesh placed intra-abdominally or to solve difficult situations, such as when the peritoneum cannot be closed during a TAPP repair for an inguinal hernia, are still being seeked. This study mimics in an animal model a situation that can be found in clinical practice during laparoscopic inguinal hernioplasty. A polypropylene mesh could be exposed to the intra-abdominal cavity even when the peritoneum is closed due to different circumstances, with no options to guarantee the prosthetic material of being exposed to the intrabdominal viscera. Different options have been suggested to solve these situations, being proposed in this study to cover the visceral surface of the mesh with an absorbable sponge containing thrombin, fibrinogen, and clotting factors (Tachosil®, Nycomed, Takeda, Osaka, Japan), to assess its use as a barrier to prevent postoperative adhesion formation., [Material and methods]: Thirty Wistar white rats (300–450 mg) were included in this study as experimental animals, being randomized into three groups (A, B, and C). We performed a bilateral prosthetic repair with conventional polypropylene mesh (2 × 2 cm, 82 kD). Prosthesis fixation was performed as follows. Group A: absorbable suture; group B: metal staples; group C: metal tackers. A piece of insulating absorbable sponge (Tachosil® 5 × 5 cm) was placed to cover the visceral surface of mesh placed at the right side of each animal. After 10 days, we performed a gross examination (by laparoscopy and laparotomy), measuring the quantity and the quality of the adhesions. Samples were taken for histopathological analysis. [Results]: Tachosil®-treated prostheses showed a statistically significant decrease in the quality of the adhesion found (p, [Conclusions]: The use of Tachosil® as a barrier material led to the absence of strong adhesions as it prevented direct contact between the mesh and the internal organs, preventing major problems associated with strong adhesions.

Although uncommon, Brucella infection can occur outside the areas of high endemicity, such as the USA. In the southern USA, hunters of wild swine are at risk for brucellosis. We present a case of a patient with fever, headache and constitutional symptoms that were ongoing for 11 months. He was diagnosed with neurobrucellosis. The patient was treated successfully with intravenous ceftriaxone, oral doxycycline and oral rifampin therapy. He had persistent neurological sequelae after completing treatment. This case illustrates the high index of suspicion needed to diagnose neurobrucellosis in a non-endemic country because initial symptoms can be subtle. The disease can be treated successfully, but long-lasting neurological sequelae are common.

Cancer cells depend on glutamine to sustain their increased proliferation and manage oxidative stress, yet glutamine is often depleted at tumor sites due to excessive cellular consumption and poor vascularization. We have previously reported that p53 protein, while a well-known tumor suppressor, can contribute to cancer cell survival and adaptation to low glutamine conditions. However, the TP53 gene is frequently mutated in tumors, and the role of mutant p53 (mutp53) in response to metabolic stress remains unclear. Here, we demonstrate that tumor-associated mutp53 promotes cancer cell survival upon glutamine deprivation both in vitro and in vivo. Interestingly, cancer cells expressing mutp53 proteins are more resistant to glutamine deprivation than cells with wild type p53 (wtp53). Depletion of endogenous mutp53 protein in human lymphoma cells leads to cell sensitivity to glutamine withdrawal, while expression of mutp53 in p53 null cells results in resistance to glutamine deprivation. Furthermore, we found that mutp53 proteins hyper-transactivate p53 target gene CDKN1A upon glutamine deprivation, thus triggering cell cycle arrest and promoting cell survival. Together, our results reveal an unidentified mechanism by which mutp53 confers oncogenic functions by promoting cancer cell adaptation to metabolic stresses.

Glioblastoma is a common aggressive primary malignant brain tumor, and is nearly universal in progression and mortality after initial treatment. Re-irradiation presents a promising treatment option for progressive disease, both palliating symptoms and potentially extending survival. Highly conformal radiation techniques such as stereotactic radiosurgery and hypofractionated radiosurgery are effective short courses of treatment that allow delivery of high doses of therapeutic radiation with steep dose gradients to protect normal tissue. Patients with higher performance status, younger age, and longer interval between primary treatment and progression represent the best candidates for re-irradiation. Multiple studies are also underway involving combinations of radiation and systemic therapy to bend the survival curve and improve the therapeutic index. In the multimodal treatment of recurrent high-grade glioma, the use of surgery, radiation, and systemic therapy should be highly individualized. Here we comprehensively review radiation therapy and techniques, along with discussion of combination treatment and novel strategies.

Ventricular tachycardia (VT) commonly occurs in patients with ischemic or nonischemic cardiomyopathy and requires antiarrhythmic drugs, ablation, or advanced circulatory support. However, life-threatening VT may be refractory to these therapies, and may cause frequent implantable cardioverter defibrillator (ICD) discharges. Left cardiac sympathetic denervation reduces the occurrence of these fatal arrhythmias by inhibiting the sympathetic outflow to the cardiac tissue. We present a 69-year-old man with nonischemic cardiomyopathy, life-threatening VT, and hemodynamic instability with numerous ICD discharges, who remained refractory to antiarrhythmic drug therapy and ablation attempts. He was effectively treated with bilateral cardiac sympathectomy. Six months later, he remained free of VT with no ICD discharges.

6579 Background: Opioid overuse is a major international public health concern. The prevalence and risk factors for chronic opioid use (COU) in radiation-induced head and neck pain are poorly understood. The aim of this study was to estimate the rates of COU and to identify risk factors for COU in head and neck cancer (HNC) patients undergoing curative-intent radiotherapy (RT) or chemoradiotherapy (CRT). Methods: We performed a systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, using the PubMed (Medline), EMBASE, and Cochrane library databases, queried from dates of inception until present. COU was defined as persistent opioid use ≥3 months after treatment completion. Studies in the English language that reported on COU in HNC patients who received RT/CRT were included. Meta-analyses were performed using random effects models. Heterogeneity was assessed using the I2 value. Results: A total of 134 studies were identified, with 7 retrospective studies (reporting on 1841 patients) meeting inclusion criteria. Median age was 59.4 years (range 56.0-62.0) with 1343 (72.9%) men and 498 (27.1%) women. Primary tumour locations included oropharynx (891, 48.4%), oral cavity (533, 29.0%), larynx (93, 5.1%), hypopharynx (32, 1.7%), and nasopharynx (29, 1.6%). 846 (46.0%) patients had stage I/II disease and 926 (50.3%) had stage III-IV disease. 301 (16.3%) patients had RT alone, 738 (40.1%) received CRT, and 594 (32.3%) underwent surgery followed by adjuvant RT/CRT. The proportion of HNC patients who received radiotherapy and developed COU was 40.7% at 3 months (95% CI 22.6%-61.7%, I2= 97.1%), 15.5% at 6 months (95% CI 7.3%-29.7%, I2= 94.3%) and 7.0% at 1 year. There were significant differences in COU based on primary tumor sites (P < 0.0001), with the highest rate (46.6%) in oropharyngeal malignancies. Other factors associated with COU included history of psychiatric disorder (61.7%), former/current alcohol abuse (53.9%), and start of opioids prior to radiation treatment (51.6%). There was no significant difference in the proportion of COU by gender (P = 0.683), disease stage (I/II vs III/IV; P = 0.443), or treatment received (RT, CRT, or adjuvant RT/CRT; P = 0.711). Conclusions: A significant proportion of patients who undergo radiotherapy for head and neck cancer suffer from COU. High-risk factors for COU include an oropharyngeal primary tumour, history of psychiatric disorder, former/current alcohol abuse, and pre-treatment opioid use. New strategies to mitigate opioid use are needed.

e17608 Background: A worldwide decline in prostate brachytherapy (BT) utilization has been reported in multiple health care settings/jurisdictions, despite strong evidence for efficacy and safety compared to other alternatives. We sought to evaluate contemporary trends in BT, EBRT and prostatectomy utilization in a publicly funded healthcare system. Methods: Men with localized prostate cancer diagnosed and treated between 2007 and 2017 in Ontario, Canada were identified using administrative data from the Institute for Clinical Evaluative Sciences. Men were coded to have received EBRT, BT (monotherapy or boost) or prostatectomy as initial definitive management. Trends were evaluated using the Cochran-Armitage test. Multivariate logistic regression was used to evaluate patient-, tumour-, and provider-factors on treatment utilization over time. Results: 57,655 men were included in our study. Prostate BT use increased from 7.5% of all treatments in 2007 to 15.4% in 2017 ( p< 0.01), primarily due to increased use of BT boost (1.7% in 2007 to 10.4% in 2017, p < 0.01). Relative to EBRT, BT use increased from 17.9% in 2007 to 28.1% in 2017 ( p< 0.01). On multivariate analysis (MVA), BT boost use increased by 28% per year (OR 1.28, 95% CI 1.26–1.31, p< 0.01) and BT monotherapy use increased by 12% per year (OR 1.12, 95% CI 1.10–1.14, p< 0.01), offset by decreasing prostatectomy use (12% per year, OR 0.88, 95% CI 0.87–0.89, p< 0.01). Comparing BT to EBRT, the strongest predictors of receiving BT were geographic residence (OR 27.6, 95% CI: 20.3–37.6, p< 0.01 between highest/lowest Local Health Integration Networks) and whether the first consulting radiation oncologist performed BT (OR 3.46, 95% CI: 3.15–3.80, p< 0.01). Other significant factors predicting BT use vs. EBRT included lower age, lower PSA, lower Charlson comorbidity score and increasing neighborhood income quintile. Low-intermediate, high-intermediate and high-risk groups were predictive of receiving BT boost, whereas BT monotherapy was predominantly used in low-risk disease. Conclusions: Contrary to trends observed in other jurisdictions, utilization of prostate BT is increasing over time in Ontario. However, substantial variation in BT utilization was found, strongly driven by both geographic region and radiation oncologist BT practice patterns. To our knowledge, this is the first study to report increasing BT utilization in the era of dose-escalated EBRT, with Ontario potentially serving as a model to promote BT utilization elsewhere.

Natural killer (NK) cells are cytotoxic lymphocytes that can rapidly kill tumor cells with exquisite specificity by antibody-dependent cell-mediated cytotoxicity (ADCC), which is exclusively mediated by the IgG Fcγ receptor CD16A. Many clinically successful therapeutic monoclonal antibodies (mAbs) utilize ADCC as a mechanism of action. However, CD16A binds IgG with low affinity and is rapidly cleaved by a proteolytic process from the cell surface upon activation, limiting therapeutic mAb efficacy. We generated NK cells expressing engineered high affinity FcγRs. Here, we investigated CD64/16A, a recombinant receptor consisting of the extracellular region of CD64, the highest affinity IgG FcγR, and the transmembrane and intracellular regions of CD16A. We expressed CD64/16A in human NK92 cells, which lack endogenous FcγRs but mediates ADCC upon expression of CD16A, and in induced pluripotent stem cells differentiated into NK (iNK) cells. We determined that CD64/16A was functional in vitro, facilitated ADCC and the production of cytokines, did not undergo rapid downregulation in expression upon NK cell activation, and facilitated conjugation to antibody-opsonized target cells. We are currently exploring an in vivo xenograft model using NSG immunocompromised mice engrafted with a HER2+ ovarian cancer cells to further examine the ADCC potency of CD64/16A iNK cells. Our findings suggest that CD64/16A may be utilized by engineered NK cells, leading to the formation of an “off-the-shelf” cellular therapy that can be combined with therapeutic mAbs for the treatment of various tumor types.

Aims Recurrent gynaecological tumours can cause significant morbidity with limited salvage options. This study investigates the strategy of salvage single-modality interstitial brachytherapy (SM-ISBT) for recurrent gynaecological pelvic cancer at two specialised ISBT centres. Materials and methods Patients who had received salvage SM-ISBT for pelvic recurrence of gynaecological cancers from September 2008 to January 2017 were included. None had distant metastasis at the time of recurrence. Local control, progression-free and overall survival and long-term toxicities were evaluated. Results Twenty-six patients with a median follow-up of 24 months (range 2.5–106.3 months) after SM-ISBT were included. Primary cancer sites were endometrium (20), cervix (4), vulva (1) and vagina (1). All patients had prior whole-pelvic external beam irradiation and 16 had prior brachytherapy. The median disease-free survival prior to SM-ISBT was 20.3 months (interquartile range 9.9–30.5). SM-ISBT was delivered with high dose rate technique over three to six fractions. The median high-risk clinical target volume was 34.6 cm3, with a median D90 of 29.1 Gy (range 16.1–64.6). The median bladder, rectum and sigmoid D2cm3 were 15.5, 18.7 and 3.7 Gy, respectively. After SM-ISBT, complete and partial responses were achieved in 17 (64%) and 5 (19%) patients, respectively. Two (7.4%) patients had grade 3 toxicities (both vaginal stenosis), with no grade 4 complications. Eighteen patients (69%) recurred, including local, regional and metastatic in 14 (54%), 8 (30%) and 5 (19%) patients, respectively. Two-year local control, progression-free survival and overall survival were 50, 38 and 78%, respectively. In follow-up, 12 patients (46%) remained in local control. Conclusions Salvage SM-ISBT re-irradiation for pelvic recurrence of gynaecological malignancies was feasible and safe. With limited salvage options, the local control obtained in more than a quarter of patients seems reasonable. Further efforts are needed to establish a consensus about the optimal patient selection, dose fractionation, implant technique and combination with systemic therapies.

High dose-rate (HDR) brachytherapy involves delivery of a high dose of radiation to the cancer with great sparing of surrounding organs at risk. Prostate cancer is thought to be particularly sensitive to radiation delivered at high dose-rate or at high dose per fraction. The rapid delivery and high conformality of dose results in lower toxicity than that seen with low dose-rate (LDR) implants. HDR combined with external beam radiotherapy results in higher cancer control rate than external beam only, and should be offered to eligible high and intermediate risk patients. While a variety of dose and fractionations have been used, a single 15 Gy HDR combined with 40-50 Gy external beam radiotherapy results in a disease-free survival of over 90% for intermediate risk and 80% for high risk. HDR monotherapy in two or more fractions (e.g., 27 Gy in 2 fractions or 34.5 Gy in 3) is emerging as a viable alternative to LDR brachytherapy for low and low-intermediate risk patients, and has less toxicity. The role of single fraction monotherapy to a dose of 19-20 Gy is evolving, with some conflicting data to date. HDR should also be considered as a salvage approach for recurrent disease following previous external beam radiotherapy. A particular advantage of HDR in this setting is the ease of delivering focal treatments, which combined with modern imaging allows focal dose escalation with minimal toxicity. Trans-rectal ultrasound (TRUS) based planning is replacing CT-based planning as the technique of choice as it minimizes or eliminates the need to move the patient between insertion, planning and treatment delivery, thus ensuring high accuracy and reproducibility of treatment.

Background Heart-sparing techniques are time and resource intensive, although not all patients require the use of these strategies. This study evaluates the performance of different distance metrics in predicting the need for breath-hold radiotherapy in left-sided breast cancer patients receiving adjuvant radiotherapy. Methods Fifty left-sided breast cancer patients treated with breast conserving surgery and adjuvant radiotherapy to the breast from a single institution were retrospectively studied. The left breast and organs at risk were contoured in accordance to guidelines and a plan with tangents was obtained using the free-breathing CT in supine position. Heart (mean heart dose (MHD), heart V25 Gy) and left anterior descending artery dosimetry were computed and compared against distance metrics under investigation (Contact Heart, 4th Arch and 5th Arch). Recursive partitioning analysis (RPA) was used to determine optimal cut-points for distance metrics for dosimetric end points. Receiver operating characteristic curves and Pearson correlation coefficients were used to evaluate the association between distance metrics and dosimetric endpoints. Univariable and multivariable logistic regression analysis was performed to identify significant predictors of dosimetric end points. Results The mean MHD and heart V25 Gy were 2.3 Gy and 10.4 cm3, respectively. With tangents, constraints for MHD (

Background Sexually transmitted Human Papilloma Virus (HPV) infection is a known risk factor for cancer of the anal canal in both men and women. Case presentation We describe a report of synchronous carcinoma of the anal canal in a heterosexual couple. High risk type 16 HPV DNA was detected in both tumors. Conclusion Longstanding sexual partners may share risk of HPV-associated anal canal cancer.

Propose: To examine the association between trial sponsorship sources, self-reported conflicts of interest (COI), and study and author characteristics in central nervous system (CNS) oncology clinical trials (CT). Methods: MEDLINE search was performed for original CT on “Central Nervous System Neoplasms“[Mesh]. The investigators assessed for relationships between funding source (industry, academic or cooperative, none, not described), COI (presented, none, or not reported), CT, and author characteristics. Results: From 2010 to 2015, 319 CT were considered eligible. The majority of the studies involved primary gliomas (55.2%) and were Phase II CT (59.2%). Drug therapy was investigated in 83.0% of the CT. The remaining studies investigated surgery or radiotherapy. A minority of papers were published in journals with impact factor (IF) higher than > 10 (16%) or in regions other than North America and Europe (20.4%). Overall, 83.1% of studies disclosed funding sources: 32.6% from industry alone, 33.9% from an academic or cooperative group, and 10.7% from a mixed funding model. COI data was reported by 85.9% of trials, of which 56.2% reported no COI and 43.8% reported a related COI. Significant predictors for sponsorship (industry and/or academia) on univariate analysis were study design, type of intervention, journal impact factor, study conclusion, transparency of COI and presence of COI. On multivariate analysis, type of intervention, (P < 0.001), journal impact factor (IF) (P = 0.003), presence of COI (P < 0.001) and study conclusion (P = 0.003) remained significant predictors of sponsorship. For predicting COI, significant variables on univariate analysis were disease type, type of intervention, journal IF, funding source, and intervention arm being related to sponsor. On multivariate analysis, disease type (P = 0.003), journal IF (P < 0.001), type of intervention (P = 0.001), and funding source (P = 0.008) remained significant. Conclusions: The majority of CNS CT reported some external funding sources and non-related COI. We identified that drug trials, higher IF, presence of COI, and a neutral or negative study conclusion are associated with external funding. Likewise drug trials, higher IF, and glioma trials are associated with presence of COI.

Anti-tumor mAbs are the most widely used and characterized cancer immunotherapy agents. Despite having a significant impact on some malignancies, most cancer patients respond poorly or develop resistance to this therapy. A known mechanism of action of these therapeutic mAbs is antibody-dependent cell-mediated cytotoxicity (ADCC), which is a primarily effector function of NK cells. CD16A on human NK cells has an exclusive role in binding to tumor-bound IgG antibodies. Though CD16A is a potent activating receptor, it is a low affinity FcγR and its cell surface levels can be rapidly downregulated by a proteolytic process involving ADAM17 upon NK cell activation, which are likely to limit the efficacy of tumor-targeting therapeutic mAbs in the tumor environment. We sought to enhance NK cell binding to anti-tumor mAbs by engineering these cells with a recombinant FcγR consisting of the extracellular region of CD64, the highest affinity IgG Fc receptor expressed by leukocytes, and the transmembrane and cytoplasmic regions of CD16A. This novel recombinant FcγR (CD64/16A) was expressed in the human NK cell line NK92 and in induced pluripotent stem cells from which primary NK cells were derived. CD64/16A also lacked the ADAM17 cleavage region in CD16A and it was not rapidly downregulated in expression following NK cell activation during ADCC. CD64/16A on NK cells facilitated conjugation to antibody-treated tumor cells, ADCC, and cytokine production, demonstrating functional activity by its two components. Unlike NK cells expressing CD16A, CD64/16A captured soluble therapeutic mAbs and the modified NK cells mediated tumor cell killing. Hence, CD64/16A could potentially be used as a docking platform on engineered NK cells for therapeutic mAbs and IgG Fc chimeric proteins, allowing for switchable targeting elements, and a novel cancer cellular therapy.

Objective As the optimal adjuvant management of stage IA serous or clear cell endometrial cancer is controversial, a multi-institutional review was conducted with the objective of evaluating the appropriateness of various strategies including observation. Methods Retrospective chart reviews for 414 consecutive patients who underwent hysterectomy for FIGO stage IA endometrial cancer with serous, clear cell or mixed histology between 2004 and 2015 were conducted in 6 North American centers. Time-to-event outcomes were analyzed by Kaplan-Meier estimates, log-rank test, univariable and multivariable cox proportional hazard regression models. Results Post-operative management included observation (50%), chemotherapy and radiotherapy (RT) (27%), RT only (16%) and chemotherapy only (7%). The 178 RT patients received external beam (EBRT, 16%), vaginal vault brachytherapy (VVB, 56%) or both (28%). Among patients without any adjuvant treatment, 5-year local control (LC), disease free survival (DFS) and cancer-specific survival (CSS) were 82% (95% confidence interval: 74–88), 70% (62–78) and 90% (82–94), respectively. CSS in patients without adjuvant treatment was improved with adequate surgical staging (100% vs. 87% (77–92), log-rank p=0.022). Adjuvant VVB was associated with improved LC (5-year 96% (91–99) vs. 84% (76–89), log-rank p=0.007) and DFS (5-year 79% (66–88) vs. 71% (63–77), log-rank p=0.033). Adjuvant chemotherapy was associated with better LC (5-year 96% (90–98) vs. 84% (77–89), log-rank p=0.014) and DFS (5-year 84% (74–91) vs. 69% (61–76), log-rank p=0.009). On multivariable analysis, adjuvant chemotherapy and VVB were associated with improved LC while adjuvant chemotherapy and age were significant for DFS. Conclusions In stage IA serous or clear cell uterine cancer, adjuvant RT and chemotherapy were associated with better LC and DFS. Observation may be appropriate in patients who have had adequate surgical staging.

BACKGROUND AND PURPOSE: Determining language dominance with fMRI is challenging in patients with brain tumor, particularly in cases of suspected atypical language representation. Supratentorial activation patterns must be interpreted with great care when the tumor is in or near the presumed language areas, where tumor tissue or mass effect can lead to false-negative fMRI results. In this study, we assessed cerebrocerebellar language fMRI lateralization in healthy participants and in patients with brain tumors with a focus on atypical language representation. MATERIALS AND METHODS: Twenty healthy participants and 38 patients with a brain tumor underwent fMRI with a verb-generation task. Cerebral and cerebellar language lateralizations were separately classified as left-sided, right-sided, or symmetric. Electrocortical stimulation was performed in 19 patients. With the McNemar test, we evaluated the dependency between language lateralization in the cerebrum and cerebellum, and with Pearson correlation analysis, the relationship between the cerebral and cerebellar lateralization indices. RESULTS: There was a significant dependency between cerebral and cerebellar language activation, with moderate negative correlation (Pearson r = −0.69). Crossed cerebrocerebellar language activation was present in both healthy participants and patients, irrespective of handedness or typical or atypical language representation. There were no discordant findings between fMRI and electrocortical stimulation. CONCLUSIONS: Language lateralization in the cerebellum can be considered an additional diagnostic feature to determine language dominance in patients with brain tumor. This is particularly useful in cases of uncertainty, such as the interference of a brain tumor with cerebral language activation on fMRI and atypical language representation.

We aimed to test any association between authors’ conclusions and self-reported COI or funding sources in central nervous system (CNS) studies. A review was performed for CNS malignancy clinical trials published in the last 5 years. Two investigators independently classified study conclusions according to authors’ endorsement of the experimental therapy. Statistical models were used to test for associations between positive conclusions and trials characteristics. From February 2010 to February 2015, 1256 articles were retrieved; 319 were considered eligible trials. Positive conclusions were reported in 56.8% of trials with industry-only, 55.6% with academia-only, 44.1% with academia and industry, 77.8% with none, and 76.4% with not described funding source (p = 0.011). Positive conclusions were reported in 60.4% of trials with unrelated COI, 60% with related COI, and 60% with no COI reported (p = 0.997). Factors that were significantly associated with the presence of positive conclusion included trials design (phase 1) [OR 11.64 (95 CI 4.66–29.09), p < 0.001], geographic location (outside North America or Europe) [OR 1.96 (95 CI 1.05–3.79), P = 0.025], primary outcomes (non-overall or progression free survival) [OR 3.74 (95 CI 2.27–6.18), p < 0.001], and failure to disclose funding source [OR 2.45 (95 CI 1.22–5.22), p = 0.011]. In a multivariable regression model, all these factors remained significantly associated with trial’s positive conclusion. Funding source and self-reported COI did not appear to influence the CNS trials conclusion. Funding source information and COI disclosure were under-reported in 14.1 and 17.2% of the CNS trials. Continued efforts are needed to increase rates of both COI and funding source reporting.

We report a case of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVD) in order to evaluate the course of an under-recognized form of cardiomyopathy with a vast array of clinical manifestations. The patient is a 49-year-old white woman transferred from an outside hospital due to dyspnea and persistent hypoxia. She had a pertinent family history that included a sister who died suddenly in her 30s from unexplained heart failure. Initial work-up for hypoxia was unrevealing. Transthoracic echocardiography revealed isolated right ventricular dysfunction with dilation and multiple trabeculations. Further investigation, including cardiac computed tomography and magnetic resonance imaging, revealed fatty infiltration into the right ventricular wall suggestive of ARVD.

Purpose Interstitial brachytherapy (ISBT) has advantages over the intracavitary techniques in the treatment of gynecological malignancies. The insertion of catheters into tumor enables higher dose conformality and normal tissue sparing. However ISBT can be associated with pain due its invasiveness. The goal of this study is to assess pain and opioid consumption of patients implanted with a perineal ISBT applicator. Methods and Materials Forty-eight patients were treated with ISBT from September 2014 to April 2016. Mean age was 63. Malignancies included 18 cervical cancers, 12 vaginal, 14 recurrent endometrial, and four others. Patient characteristics and technical ISBT data were collected. Opioid consumption was quantified as oral morphine equivalent per day (OMEq/day) from postimplant until removal. Pain score levels were collected by using an 11-point scoring system. Results Twenty-three patients had a single ISBT implantation, whereas 25 had a second. Twenty-eight patients required IV-patient-controlled analgesia. Mean OMEq/day for the first insertion was 55 mg. In the second insertion, an increase of 22 mg was seen (p = 0.0004). Patients with IV-patient-controlled analgesia had higher opioid consumption (OMEq/day 69.8 mg vs 32.1 mg, p = 0.001) and maximum pain scores (5.5 vs 3.4, p = 0.007) as compared with patients on oral opioids. Higher levels of pain were detected in the first hours postimplant. Previous opioids and age were associated with increased opioid consumption. Conclusions Pain from perineal-ISBT can be managed with oral opioids in a select group of patients. For repeat insertions, there may be an increase in opioid consumption. While age and previous opioids affected opioid requirements, other factors such as number of needles and insertion depth were not associated factors.