Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer (TOPAZ-1): patient-reported outcomes from a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: In the ongoing, randomised, double-blind phase 3 TOPAZ-1 study, durvalumab, a PD-L1 inhibitor, plus gemcitabine and cisplatin was associated with significant improvements in overall survival compared with placebo, gemcitabine, and cisplatin in people with advanced biliary tract cancer at the pre-planned intermin analysis. In this paper, we present patient-reported outcomes from TOPAZ-1. METHODS: In TOPAZ-1 (NCT03875235), participants aged 18 years or older with previously untreated, unresectable, locally advanced, or metastatic biliary tract cancer with an Eastern Cooperative Oncology Group performance status of 0 or 1 and one or more measurable lesions per Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1) were randomly assigned (1:1) to the durvalumab group or the placebo group using a computer-generated randomisation scheme. Participants received 1500 mg durvalumab or matched placebo intravenously every 3 weeks (on day 1 of the cycle) for up to eight cycles in combination with 1000 mg/m2 gemcitabine and 25 mg/m2 cisplatin intravenously on days 1 and 8 every 3 weeks for up to eight cycles. Thereafter, participants received either durvalumab (1500 mg) or placebo monotherapy intravenously every 4 weeks until disease progression or other discontinuation criteria were met. Randomisation was stratified by disease status (initially unresectable vs recurrent) and primary tumour location (intrahepatic cholangiocarcinoma vs extrahepatic cholangiocarcinoma vs gallbladder cancer). Patient-reported outcomes were assessed as a secondary outcome in all participants who completed the European Organisation for Research and Treatment of Cancer's 30-item Quality of Life of Cancer Patients questionnaire (QLQ-C30) and the 21-item Cholangiocarcinoma and Gallbladder Cancer Quality of Life Module (QLQ-BIL21). We calculated time to deterioration-ie, time from randomisation to an absolute decrease of at least 10 points in a patient-reported outcome that was confirmed at a subsequent visit or the date of death (by any cause) in the absence of deterioration-and adjusted mean change from baseline in patient-reported outcomes. FINDINGS: Between April 16, 2019, and Dec 11, 2020, 685 participants were enrolled and randomly assigned, 341 to the durvalumab group and 344 to the placebo group. Overall, 345 (50%) of participants were male and 340 (50%) were female. Data for the QLQ-C30 were available for 318 participants in the durvalumab group and 328 in the placebo group (median follow-up 9·9 months [IQR 6·7 to 14·1]). Data for the QLQ-BIL21 were available for 305 participants in the durvalumab group and 322 in the placebo group (median follow-up 10·2 months [IQR 6·7 to 14·3]). The proportions of participants in both groups who completed questionnaires were high and baseline scores were mostly similar across treatment groups. For global health status or quality of life, functioning, and symptoms, we noted no difference in time to deterioration or adjusted mean changes from baseline were observed between groups. Median time to deterioration of global health status or quality of life was 7·4 months (95% CI 5·6 to 8·9) in the durvalumab group and 6·7 months (5·6 to 7·9) in the placebo group (hazard ratio 0·87 [95% CI 0·69 to 1·12]). The adjusted mean change from baseline was 1·23 (95% CI -0·71 to 3·16) in the durvalumab group and 0·35 (-1·63 to 2·32) in the placebo group. INTERPRETATION: The addition of durvalumab to gemcitabine and cisplatin did not have a detrimental effect on patient-reported outcomes. These results suggest that durvalumab, gemcitabine, and cisplatin is a tolerable treatment regimen in patients with advanced biliary tract cancer. FUNDING: AstraZeneca.

Patient-Reported Outcomes From the Phase III HIMALAYA Study of Tremelimumab Plus Durvalumab in Unresectable Hepatocellular Carcinoma.

PURPOSE: In the phase III HIMALAYA study (ClinicalTrials.gov identifier: NCT03298451) in unresectable hepatocellular carcinoma (uHCC), the Single Tremelimumab Regular Interval Durvalumab (STRIDE) regimen significantly improved overall survival versus sorafenib, and durvalumab monotherapy was noninferior to sorafenib. Patient-reported outcomes (PROs), a secondary outcome from HIMALAYA, are reported here. METHODS: Participants were randomly assigned to receive STRIDE, durvalumab, or sorafenib. PROs were assessed (preplanned secondary outcome) using the European Organization for Research and Treatment of Cancer 30-item Quality of Life Questionnaire and the 18-item HCC module. Time to deterioration (TTD), change from baseline and improvement rate in global health status/quality of life (GHS/QoL), functioning, and disease-related symptoms were analyzed. RESULTS: In total, 1,171 participants were randomly assigned to STRIDE (n = 393), durvalumab (n = 389), or sorafenib (n = 389) and were evaluable for PRO assessments. Across treatment arms, compliance rates for PROs were >77% at baseline and >70% overall. Baseline scores were comparable across treatment arms. TTD in GHS/QoL, physical functioning, fatigue, appetite loss, and abdominal pain was numerically longer for both STRIDE and durvalumab versus sorafenib. Clinically meaningful deterioration in PROs was not observed in any treatment arm. However, TTD in nausea and abdominal swelling was numerically longer for STRIDE versus sorafenib, and the likelihood of clinically meaningful improvement in GHS/QoL, role, emotional and social functioning, and disease-related symptoms was greater with STRIDE and durvalumab versus sorafenib. PROs with STRIDE and durvalumab were generally similar. CONCLUSION: Compared with sorafenib, STRIDE and durvalumab were associated with clinically meaningful, patient-centered GHS/QoL, functioning, and symptom benefits in people with uHCC. These findings support the benefits of the STRIDE regimen compared with sorafenib for a diverse population reflective of the global uHCC population.

'AJ's Orbicularis Oris Stitch: A Novel and Simple Technique of Reconstructing Central Arch Mandibular Defects in Resource-Constrained Set Up'.

Lip and oral cavity SCC account for 2nd highest incidence of cancers and 3rd most common cause of mortality from cancer in India. Reconstruction of defects of central arch invading cancers results in poor cosmetic and functional outcomes if free flaps are not used. 30 patients with Oral SCC in the age group 20-75 years requiring central arch segmental mandibulectomy were included. Reconstruction was done with pedicled bipaddled PMMC flap with 'AJ's orbicularis oris stitch' using Fiber wire. Patients were divided into 4 groups according to extent of lip and skin loss post excision of primary tumour. Patients were evaluated with subjective scores for drooling, oral competence and cosmesis. There were 4, 12, 9 and 5 patients in Group A, B, C and D respectively. Mean subjective scores using our technique for drooling, oral competence and cosmesis were 3.75/4,3.75/4 and 3.5/4 for group A, 3.45/4, 3.36/4 and 3.09/4 for group B, 2.8/4, 2.6/4 and 2.3/4 for group C defects and 2.5/4, 3/4 and 2.5/4 for group D defects respectively. Over all scores for all patients were 3.2/4, 3.14/4 and 2.84/4 for drooling, oral competence and cosmesis. This simple, quick and inexpensive technique of reconstruction of central mandibular arch defects can drastically improve cosmetic and functional outcomes in a resource restrained set up. However, long term results and comparison studies are required for standardisation of the technique.

Preferred practice patterns and review on rosacea.

Rosacea is a chronic, inflammatory facial dermatosis commonly found in fair skin tone population. Recent studies have shown the increasing prevalence in the dark skin tone population as well. Ocular involvement is very common and can occur without cutaneous features. Common ocular features are chronic blepharoconjunctivitis with eyelid margin inflammation and meibomian gland dysfunction. Corneal complications include corneal vascularization, ulceration, scarring, and rarely, perforation. Diagnosis is largely based on clinical signs, although it is often delayed in the absence of cutaneous changes, particularly in children. The management ranges from local therapy to systemic treatment, depending on the severity of the disease. There is a positive association between demodicosis and rosacea; however, causality is always argued. In this review, we describe the epidemiology, clinical features, and treatment of rosacea and ocular rosacea.

External ventricular drainage in the management of pediatric patients with posterior fossa tumors and hydrocephalus: a retrospective cohort study.

PURPOSE: To determine whether intraoperative adjunctive EVD placement in patients with a posterior fossa tumor (PFT) led to improved surgical, radiographic, and clinical outcomes compared to those who did not receive an EVD. METHODS: Patients were grouped as those who underwent routine intraoperative adjunctive EVD insertion and those who did not at time of PFT resection. Patients who pre-operatively required a clinically indicated EVD insertion were excluded. Comparative analyses between both groups were conducted to evaluate clinical, radiological, and pathological outcomes. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were computed for post-operative outcomes. RESULTS: Fifty-five selected patients were included, 15 who had an EVD placed at the time of PFT resection surgery, and 40 who did not. Children without an EVD did not experience a higher rate of complications or poorer post-operative outcomes compared to those with an EVD placed during resection surgery. There was no significant difference in the degree of gross total resection (p = 0.129), post-operative CSF leak (p = 1.000), and post-operative hemorrhage (p = 0.554) between those with an EVD and those without. The frequency of new cranial nerve deficits post-operatively was higher in those with an EVD (40%) compared to those without (3%, p = 0.001). There was a trend towards more frequently observed post-operative hydrocephalus in the EVD group (p = 0.057). CONCLUSION: The routine use of EVD as an intraoperative adjunct in clinically stable pediatric patients with posterior fossa tumors and hydrocephalus may not be associated with improved radiological or clinical outcomes.

Advancing Digital Health Innovation in Oncology: Priorities for High-Value Digital Transformation in Cancer Care.

Although health care delivery is becoming increasingly digitized, driven by the pursuit of improved access, equity, efficiency, and effectiveness, progress does not appear to be equally distributed across therapeutic areas. Oncology is renowned for leading innovation in research and in care; digital pathology, digital radiology, real-world data, next-generation sequencing, patient-reported outcomes, and precision approaches driven by complex data and biomarkers are hallmarks of the field. However, remote patient monitoring, decentralized approaches to care and research, "hospital at home," and machine learning techniques have yet to be broadly deployed to improve cancer care. In response, the Digital Medicine Society and Moffitt Cancer Center convened a multistakeholder roundtable discussion to bring together leading experts in cancer care and digital innovation. This viewpoint highlights the findings from these discussions, in which experts agreed that digital innovation is lagging in oncology relative to other therapeutic areas. It reports that this lag is most likely attributed to poor articulation of the challenges in cancer care and research best suited to digital solutions, lack of incentives and support, and missing standardized infrastructure to implement digital innovations. It concludes with suggestions for actions needed to bring the promise of digitization to cancer care to improve lives.

Health-Related Quality of Life of Patients with Metastatic Pancreatic Cancer: A Systematic Literature Review.

Background: Metastatic pancreatic cancer (mPaC) has a poor prognosis and available treatments provide only moderate improvements in survival. Preserving or improving health-related quality of life (HRQoL) is therefore an important treatment outcome for patients with mPaC. This systematic review identified HRQoL data in patients with mPaC before and after treatment, compared these with data from the general population, and reported the effects of different mPaC treatments on HRQoL. Methods: Searches were performed in Embase, PubMed, and the Cochrane Library from January 2008 to May 2021, and the articles identified were screened for HRQoL data in patients with mPaC. Abstracts from relevant congresses were also manually searched. Publications included were randomized controlled trials and observational studies written in English that reported HRQoL data for adult patients with non-resectable mPaC who were on or off treatment. Results: Thirty relevant publications were identified and HRQoL scores were collected. Overall, baseline mean scores from the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), 5-dimension EuroQol questionnaire (EQ-5D), and Functional Assessment of Cancer Therapy-General (FACT-G) for newly diagnosed and previously treated patients with mPaC were worse than those of the general population. Baseline scores were generally better for previously treated patients than for newly diagnosed patients, indicating that mPaC treatments preserve or improve HRQoL. Identified publications also reported changes in HRQoL following first- or subsequent-line chemotherapy. When reported, 10 studies found improvements in overall HRQoL compared with baseline scores, four reported no changes in overall HRQoL after treatment, and six found deteriorations in overall HRQoL. Conclusion: Patients with mPaC had worse HRQoL than the general population. Available anti-cancer therapies can improve or preserve HRQoL.

Natural Language Processing for Automated Classification of Qualitative Data From Interviews of Patients With Cancer.

OBJECTIVES: This study sought to explore the use of novel natural language processing (NLP) methods for classifying unstructured, qualitative textual data from interviews of patients with cancer to identify patient-reported symptoms and impacts on quality of life. METHODS: We tested the ability of 4 NLP models to accurately classify text from interview transcripts as "symptom," "quality of life impact," and "other." Interview data sets from patients with hepatocellular carcinoma (HCC) (n = 25), biliary tract cancer (BTC) (n = 23), and gastric cancer (n = 24) were used. Models were cross-validated with transcript subsets designated for training, validation, and testing. Multiclass classification performance of the 4 models was evaluated at paragraph and sentence level using the HCC testing data set and analyzed by the one-versus-rest technique quantified by the receiver operating characteristic area under the curve (ROC AUC) score. RESULTS: NLP models accurately classified multiclass text from patient interviews. The Bidirectional Encoder Representations from Transformers model generally outperformed all other models at paragraph and sentence level. The highest predictive performance of the Bidirectional Encoder Representations from Transformers model was observed using the HCC data set to train and BTC data set to test (mean ROC AUC, 0.940 [SD 0.028]), with similarly high predictive performance using balanced and imbalanced training data sets from BTC and gastric cancer populations. CONCLUSIONS: NLP models were accurate in predicting multiclass classification of text from interviews of patients with cancer, with most surpassing 0.9 ROC AUC at paragraph level. NLP may be a useful tool for scaling up processing of patient interviews in clinical studies and, thus, could serve to facilitate patient input into drug development and improving patient care.

Health-related quality of life scores of metastatic pancreatic cancer patients responsive to first line chemotherapy compared to newly derived EORTC QLQ-C30 reference values.

BACKGROUND: Metastatic pancreatic cancer (mPC) and its treatments significantly impact health-related quality of life (HRQoL). POLO, a randomized, double-blind, placebo-controlled phase 3 trial evaluated the efficacy of olaparib as maintenance therapy in germline BRCA mutated mPC patients who had not progressed during ≥16 weeks of first-line platinum-based chemotherapy. HRQoL was assessed using the EORTC QLQ-C30. To enhance score interpretation, we derived reference values for treatment-naïve mPC patients from the literature. METHODS: A targeted literature review identified EORTC QLQ-C30 baseline values in treatment-naïve mPC patients. Reference values were calculated by deriving means from studies meeting inclusion criteria, with scores from 0 to 100 (higher scores indicate better QoL/functioning but worse symptoms). For POLO patients, means were calculated using pooled baseline data across study arms. RESULTS: Four studies met inclusion criteria. Depending on the specific scale, sample sizes ranged from n = 466 to n = 639. Compared to newly derived reference values, POLO patients reported markedly better HRQoL scores at baseline across most scales, with eight scales showing differences of ≥10 points. POLO patients' HRQoL scores were often close to or better than general population norm data. CONCLUSIONS: This is the first study to systematically derive EORTC QLQ-C30 reference values for mPC. POLO patients had better HRQoL scores than those in the literature and similar to general population data. Comparatively high HRQoL of POLO patients are likely due to effects of prior first-line treatment and resolution of chemotherapy-related symptoms, response shift, or a combination. Newly derived reference values can enhance interpretation of mPC patients' HRQoL. TRIAL REGISTRATION: The POLO trial was registered on 9 July 2014 with ClinicalTrials.gov as NCT02184195.

Understanding the patient experience in hepatocellular carcinoma: a qualitative patient interview study.

PURPOSE: This study aimed to elucidate the patient experience of hepatocellular carcinoma (HCC) to guide patient-centered outcome measurement in drug development. METHODS: Patients with HCC participated in qualitative interviews to elicit disease-related signs/symptoms and impacts, using discussion guides developed from literature searches and discussions with oncologists. Interview participants rated the disturbance of their experiences (0-10 scale). A conceptual model was developed and mapped against patient-reported outcome (PRO) instruments identified from database reviews. RESULTS: Interviews were conducted with 25 individuals with HCC (68% were men; median age: 63 years; 12% Barcelona clinic liver cancer (BCLC) stage A; 32% stage B; and 56% stage C) in the USA. Fifty-one HCC-related concepts were identified from the interviews and were grouped into eight sign/symptom categories (eating behavior/weight changes; extremities [arms, legs]; fatigue and strength; gastrointestinal; pain; sensory; skin; other) and four impact categories (emotional; physical; cognitive function; other) for the conceptual model. The most prevalent and disturbing experiences across the disease stages were fatigue/lack of energy and emotional impacts such as frustration, fear, and depression. Abdominal pain and skin-related issues were particularly common and disturbing in individuals with HCC stage C. The EORTC QLQ-C30 and HCC18 were identified as commonly used PRO instruments in HCC studies and captured the relevant signs/symptoms associated with the patient experience. CONCLUSION: Patients with HCC reported a range of signs/symptoms and impacts that negatively affect daily functioning and quality of life. Including PRO measures in HCC clinical trials can provide meaningful patient perspectives during drug development.

Biomarkers of Coagulation and Inflammation in COVID-19-Associated Ischemic Stroke.

[Figure: see text].

Understanding Patient Experience in Biliary Tract Cancer: A Qualitative Patient Interview Study.

INTRODUCTION: Patients living with biliary tract cancer (BTC) experience a decline in health-related quality of life (HRQoL). This study aimed to obtain a comprehensive understanding of the patient experience of BTC-related signs/symptoms and the impacts of these on daily functioning and HRQoL. METHODS: Patients with BTC participated in qualitative semi-structured concept elicitation interviews. Signs/symptoms and impacts of BTC were initially explored by targeted literature searches and interviews with five clinicians. Patient interviews were transcribed and coded using qualitative research software. Concept saturation was assessed over five interview waves. A sign/symptom or impact was defined as "salient" if mentioned by ≥ 50% of patients, with a mean disturbance rating of ≥ 5 (0-10 scale). A conceptual model of the patient experience of BTC-related signs/symptoms and impacts was produced. RESULTS: Twenty-three patients from the USA (78% women; median age: 54 years), diagnosed as having early (n = 3), locally advanced (n = 11) or metastatic (n = 9) disease, were interviewed. Sixty-six signs/symptoms and 12 impacts were identified. Of these, 46 signs/symptoms and 8 impacts were not identified from the targeted literature or clinician interviews. Concept saturation was reached by the fourth of five interview waves. Fourteen disease-related signs/symptoms (including fatigue/lack of energy, abdominal pain, lack of appetite, insomnia and diarrhoea) and three impacts (physical, emotional and cognitive impacts) were deemed "salient". The conceptual model included 50 signs/symptoms and 12 impacts. CONCLUSION: Patients with BTC reported a range of signs/symptoms and impacts that negatively affect daily functioning and HRQoL.

CNS demyelination associated with immune dysregulation and a novel CTLA-4 variant.

BACKGROUND: The cytotoxic T-lymphocyte antigen-4 (CTLA-4) pathway acts as a negative immune regulator of T-cell activation and promotes self-tolerance. CASE: We report the first case of biopsy-proven central nervous system inflammatory demyelination in the context of primary immunodeficiency and a novel CTLA-4 variant. CONCLUSION: This case has significant implications for the development of novel treatments for autoimmune conditions including multiple sclerosis and further emphasises the need for caution with clinical use of CTLA-4 immune checkpoint inhibitors in those with a history of inflammatory demyelination.

Patient-Reported Outcomes with Durvalumab With or Without Tremelimumab Versus Standard Chemotherapy as First-Line Treatment of Metastatic Non-Small-Cell Lung Cancer (MYSTIC).

BACKGROUND: The phase 3 MYSTIC study of durvalumab ± tremelimumab versus chemotherapy in metastatic non-small-cell lung cancer (NSCLC) patients with tumor cell (TC) programmed cell death ligand 1 (PD-L1) expression ≥ 25% did not meet its primary endpoints. We report patient-reported outcomes (PROs). PATIENTS AND METHODS: Treatment-naïve patients were randomized (1:1:1) to durvalumab, durvalumab + tremelimumab, or chemotherapy. PROs were assessed in patients with PD-L1 TC ≥ 25% using EORTC Quality of Life Questionnaire (QLQ)-C30/LC13. Changes from baseline (12 months) for prespecified PRO endpoints of interest were analyzed by mixed model for repeated measures (MMRM) and time to deterioration (TTD) by stratified log-rank tests. RESULTS: There were no between-arm differences in baseline PROs (N = 488). Between-arm differences in MMRM-adjusted mean changes from baseline favored at least one of the durvalumab-containing arms versus chemotherapy (nominal P < .01) for C30 fatigue: durvalumab (-9.5; 99% confidence interval [CI], -17.0 to -2.0), durvalumab + tremelimumab (-11.7; 99% CI, -19.4 to -4.1); and for C30 appetite loss: durvalumab (-11.9; 99% CI, -21.1 to -2.7). TTD was longer with at least one of the durvalumab-containing arms versus chemotherapy (nominal P < .01) for global health status/quality of life: durvalumab (hazard ratio [HR] = 0.7; 95% CI, 0.5-1.0), durvalumab + tremelimumab (HR = 0.7; 95% CI, 0.5-1.0); and for physical functioning: durvalumab (HR = 0.6; 95% CI, 0.4-0.8), durvalumab + tremelimumab (HR = 0.6; 95% CI, 0.5-0.9) (both C30); as well as for the key symptoms of dyspnea: durvalumab (HR = 0.6; 95% CI, 0.5-0.9), durvalumab + tremelimumab (HR = 0.7; 95% CI, 0.5-1.0) (both LC13); fatigue: durvalumab + tremelimumab (HR = 0.6; 95% CI, 0.4-0.8); and appetite loss: durvalumab (HR = 0.5; 95% CI, 0.4-0.7), durvalumab + tremelimumab (HR = 0.7; 95% CI, 0.5-0.9) (both C30). CONCLUSION: Durvalumab ± tremelimumab versus chemotherapy reduced symptom burden and improved TTD of PROs, suggesting it had no detrimental effects on quality of life in metastatic NSCLC patients.

Multicentre, clinical trial of burst spinal cord stimulation for neck and upper limb pain NU-BURST: a trial protocol.

BACKGROUND: Spinal cord stimulation (SCS) is an established therapy for chronic neuropathic pain and most frequently utilised for Failed Back Surgery Syndrome (FBSS). BurstDR™ also known as DeRidder Burst-SCS, a novel waveform, has demonstrated superiority to conventional tonic stimulation of the thoracic spine in FBSS. There are case reports of an improvement in multidimensional pain outcomes using DeRidder Burst-SCS in the cervical spine for chronic neck and cervical radicular pain. The safety and efficacy of cervical DeRidder Burst-SCS stimulation still however remain undetermined. METHODS/DESIGN: This is a prospective, multicentre feasibility trial evaluating the safety and therapeutic efficacy of DeRidder Burst-SCS stimulation for the treatment of chronic intractable neck pain with or without radiation to the arm, shoulder, and upper back. After baseline evaluation, subjects will undergo an SCS trial using the Abbott Invisible Trial system according to standard clinical procedures. During the trial phase, SCS leads will be implanted in the cervical epidural space. At the end of the SCS trial, subjects experiencing at least 50% pain relief will be considered for permanent implant. Pain intensity, medication usage, and other multidimensional pain outcomes will be collected. The timing of these will be at baseline, end of the SCS trial and at 3-, 6-, and 12-month visits. Incidence of adverse events will be collected throughout the study duration. DISCUSSION: The results of this feasibility study will validate the efficacy and safety of DeRidder Burst-SCS stimulation in the cervical spine. The results obtained in this study will potentially be used to generate a level 1 evidence-based study with formal statistical hypotheses testing. TRIAL REGISTRATION: www.clinicaltrials.gov Identifier: NCT03159169.

Hypoplastic left heart syndrome with anomalous origin of right pulmonary artery.

Classic hypoplastic left heart syndrome is a rare but fatal congenital heart disease associated with variable underdevelopment of the left side of the heart. Complex forms of hypoplastic left heart syndrome have been reported to coexist with anomalous pulmonary venous drainage, transposition of the great arteries, or pulmonary valve dysplasia. We report a case of hypoplastic left heart syndrome with anomalous origin of the right pulmonary artery from the ascending aorta a rare association not reported in the literature. Preoperative comprehensive echocardiography is essential for diagnosis and accurate recognition of such rare anatomic variations.

Deep Brain Stimulation for Facial Pain.

Electro-modulation of subcortical deep brain structures by surgically implanted electrodes is now standard evidence-based treatment for movement disorders such as Parkinson's disease and essential tremor and is approved for dystonia and obsessive-compulsive disorder under a humanitarian exemption. Historically, deep brain stimulation (DBS) for multiple indications has demonstrated acceptable complication rates, rare mortality, and reducing morbidity as the technology and the techniques of its application have advanced. DBS for the amelioration of pain has been performed since the early 1950s, and became widely used in the 1970s, when targeting the somatosensory thalamus was shown to be efficacious for intractable pain syndromes including facial pain. The technique fell out of favour in the late 1990s after 2 multicentre trials failed to meet end-point criteria. Since these trials, DBS for pain has remained for investigational or "off-label" use. Criticisms from previous literature have involved unsuitability of patient selection, as well as inconsistencies in neurosurgical technique. Clinical success with DBS for facial pain has been for the treatment of a variety of chronic neuropathic and nociceptive pain syndromes; including trigeminal neuropathy, post-herpetic neuralgia, deafferentation facial pain, "atypical" facial pain, cluster headaches and other trigeminal autonomic cephalalgias, as well as head and neck pathologies, most often which have been resistant to all other 1st- and 2nd-line medical and surgical treatments, when DBS has become a "last treatment option." An enhanced understanding of the mechanisms of action of DBS for pain will enhance outcome, and appropriately prescribe evolving novel nuclear brain targets.

Patient-reported outcomes with first-line durvalumab plus platinum-etoposide versus platinum-etoposide in extensive-stage small-cell lung cancer (CASPIAN): a randomized, controlled, open-label, phase III study.

OBJECTIVES: In the phase III CASPIAN study, first-line durvalumab plus etoposide in combination with either cisplatin or carboplatin (EP) significantly improved overall survival (primary endpoint) versus EP alone in patients with extensive-stage small-cell lung cancer (ES-SCLC) at the interim analysis. Here we report patient-reported outcomes (PROs). MATERIALS AND METHODS: Treatment-naïve patients with ES-SCLC received 4 cycles of durvalumab plus EP every 3 weeks followed by maintenance durvalumab every 4 weeks until progression, or up to 6 cycles of EP every 3 weeks. PROs, assessed with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) version 3 and its lung cancer module, the Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13), were prespecified secondary endpoints. Changes from baseline to disease progression or 12 months in prespecified key disease-related symptoms (cough, dyspnea, chest pain, fatigue, appetite loss) were analyzed with a mixed model for repeated measures. Time to deterioration (TTD) of symptoms, functioning, and global health status/quality of life (QoL) from randomization was analyzed. RESULTS: In the durvalumab plus EP and EP arms, 261 and 260 patients were PRO-evaluable. Patients in both arms experienced numerically reduced symptom burden over 12 months or until progression for key symptoms. For the improvements from baseline in appetite loss, the between-arm difference was statistically significant, favoring durvalumab plus EP (difference, -4.5; 99% CI: -9.04, -0.04; nominal p = 0.009). Patients experienced longer TTD with durvalumab plus EP versus EP for all symptoms (hazard ratio [95% CI] for key symptoms: cough 0.78 [0.600‒1.026]; dyspnea 0.79 [0.625‒1.006]; chest pain 0.76 [0.575‒0.996]; fatigue 0.82 [0.653‒1.027]; appetite loss 0.70 [0.542‒0.899]), functioning, and global health status/QoL. CONCLUSION: Addition of durvalumab to first-line EP maintained QoL and delayed worsening of patient-reported symptoms, functioning, and global health status/QoL compared with EP.

Intraoperative intravenous ibuprofen use is not associated with increased post-tonsillectomy bleeding.

OBJECTIVES: Intravenous (IV) ibuprofen was approved by the FDA for use in pediatric patients in November 2015. The objective of this study was to compare bleeding rates in pediatric tonsillectomy patients who received intraoperative intravenous ibuprofen versus those who did not. Secondary objectives included analyzing factors that correlated with return to the Emergency Department (ED) for pain or dehydration. METHODS: Charts were reviewed for all patients 0-18 years of age who underwent a tonsillectomy with or without adenoidectomy at a tertiary care children's hospital from 1/1/2017 through 5/21/2018. Demographic information and perioperative medications including the use of intraoperative intravenous ibuprofen were recorded. ED visits and operating room (OR) returns for bleeding were tracked for up to 30 days after surgery. RESULTS: 1085 charts were analyzed. Intraoperative IV ibuprofen was used in 132 cases (12.2%). Primary bleeds, defined as bleeding within 24 h of surgery, occurred in 1 (0.76%) of 132 patients who received IV ibuprofen, and 1 (0.10%) of 953 patients who did not receive IV ibuprofen. Secondary bleeds, defined as bleeds after 24 h from surgery occurred in 2 (1.52%) of 132 patients who received IV ibuprofen and 38 (3.99%) of 953 patients who did not receive IV ibuprofen. No statistical difference was found between the two groups in rates of overall (primary plus secondary) bleeding requiring return to ED (p = 0.759) or return to OR (p = 0.710). CONCLUSION: The observed bleeding rate after pediatric tonsillectomy was not statistically different in patients who received intraoperative IV ibuprofen versus those who did not receive this medication. LEVEL OF EVIDENCE: III.

Curvularia infection of corneoscleral tunnel.

Corneoscleral tunnel infection is a potentially sight threatening complication of cataract surgery. Microbiological investigations are mandatory and early surgical intervention helps in achieving favourable outcomes. Fungal infection of tunnel incisions can pose a diagnostic and therapeutic challenge. We report a case of post-operative tunnel infection with curvularia. Prompt surgical intervention and intensive topical therapy helped attain a good tectonic as well as visual recovery.