Changing Therapeutic Landscape Research Articles

Assessing disease activity in scleroderma-related interstitial lung disease: a review and practical guide to management.

Systemic sclerosis (SSc) is a heterogeneous disease with a propensity to involve multiple organ systems. There is a significant proportion of these patients with interstitial lung disease (ILD) who are at risk of mortality and morbidity. There are limited available tools to assess the severity of parenchymal lung involvement and are subject to confounding factors, including the presence of pulmonary hypertension and concomitant smoking history. The diagnostic tools include careful clinical history, examination, thoracic imaging, and pulmonary function tests. One of the limitations of assessing disease severity in SSc-ILD is the lack of standardized definitions for disease activity and serum biomarkers to predict future progression. Although there has been significant progress in managing SSc-related ILD over the last couple of decades with a few randomized double-blind clinical trials assessing the role of immunosuppression (mainly Cyclophosphamide and Mycophenolate Mofetil), the efficacy of these therapies is at best modest and is associated with significant toxicities. Furthermore, Nintedanib has shown promise in reducing forced vital capacity decline in SSc-ILD and in progressive fibrotic-ILD of a range of etiologies. Data are emerging for therapies like Rituximab and Tocilizumab, and we are likely to see further evidence of similar drugs being efficacious in this disease cohort. A relatively simplified algorithm is proposed in this review to guide clinicians dealing with ILD and SSc. It is imperative that clinicians take a multi-disciplinary approach to managing this complex disease in a changing therapeutic landscape.

A Podcast on Practical Considerations in Patients with Advanced Urothelial Cancer Receiving First-Line Cisplatin- or Carboplatin-Based Chemotherapy Followed by Avelumab Maintenance in a Changing Therapeutic Landscape.

Platinum-based chemotherapy has been the cornerstone of first-line treatment for advanced urothelial carcinoma for decades, based on its proven efficacy and well-characterized safety profile. Although enfortumab vedotin (EV) plus pembrolizumab showed superior efficacy versus platinum-based chemotherapy in the EV-302 phase 3 trial, common and potentially cumulative toxicities associated with EV plus pembrolizumab may make this combination less suitable for some patients, such as those with pre-existing neuropathy, hyperglycemia, or hepatic impairment, or patients likely to have favorable outcomes with platinum-based chemotherapy. The availability of EV plus pembrolizumab in various countries may also be limited by financial considerations. Thus, platinum-based chemotherapy is likely to remain a valuable option for advanced urothelial carcinoma. Eligibility for cisplatin- or carboplatin-based regimens can be determined by assessing renal function, performance status, and specific comorbidities. In cisplatin-eligible and -ineligible patients without disease progression following platinum-based chemotherapy, avelumab first-line maintenance is standard of care based on findings from the JAVELIN Bladder 100 phase 3 trial, which showed that avelumab first-line maintenance plus best supportive care prolonged overall survival and progression-free survival compared with best supportive care alone across clinically relevant subgroups. Adverse events associated with avelumab were generally consistent with those observed with other immune checkpoint inhibitors, and long-term follow-up showed no new safety concerns with prolonged treatment. Efficacy benefits and safety profiles were similar in patients who received avelumab first-line maintenance after cisplatin- or carboplatin-based chemotherapy. The effectiveness and safety of avelumab first-line maintenance have been confirmed in several real-world studies. Overall, these data support the use of avelumab first-line maintenance for all platinum-treated patients without disease progression. In this podcast, we discuss the evolving role of platinum-based chemotherapy in this disease setting in the context of EV-302 trial results and describe practical considerations in patients receiving first-line cisplatin- or carboplatin-based chemotherapy followed by avelumab maintenance therapy.

Copanlisib in Combination with Nivolumab in Subjects with Relapsed/Refractory Diffuse Large B-Cell Lymphoma and Primary Mediastinal Large B-Cell Lymphoma: A Phase II Study

Introduction: Diffuse Large B-cell Lymphoma (DLBCL) are aggressive B-cell non-Hodgkin lymphomas (NHL). One particular subtype, Primary Mediastinal B-cell Lymphoma (PMBCL), is often grouped with DLBCL, but it possesses distinct biological and clinical characteristics. While initial therapy successfully cures approximately two-thirds of patients (pts), those who do not respond or experience progression within the first two years have a poor prognosis despite novel cellular therapies and bispecifics and ultimately succumb to their disease. There is a pressing need for more effective therapeutic approaches in this patient population. Recent advances in the understanding of DLBCL pathogenesis have led to the targeting of various signaling pathways, including the PI3K-AKT-mTOR pathway. One such drug, copanlisib (C), a pan-PI3K inhibitor with potent PI3K-α/PI3K-δ inhibition, exhibited activity in both indolent and aggressive NHL. In preclinical studies using a DLBCL mouse model, treatment with C effectively reduced the immunosuppressive tumor-infiltrating T-regulatory cells (Tregs). Moreover, when combined with a surrogate anti-mouse programmed death -1 (PD-1) blocker, C demonstrated significant in vivo responses (75%) compared to the monotherapy groups (0%). These findings support the rationale for exploring the combination of nivolumab, a PD-1 blocker, and copanlisib (C-N) in DLBCL. Thus, a phase 2 prospective study has been developed, focusing on two relapsed/refractory (RR) cohorts (DLBCL and PMBCL), treated with the combination of C-N. A prespecified interim analysis was planned upon enrollment of 14 pts. Herein, we report outcomes of the 12 enrolled pts, as the study was halted prematurely due to a safety signal deemed possibly related to the combination. Study design: C 60 mg was given intravenously on days 1, 8, and 15 during cycles 1-8, and on days 1 and 15 in subsequent cycles. N 240 mg IV was given on days 1 and 15 during cycles 1-8, and 480 mg on day 1 on subsequent cycles. Each treatment cycle is 28 days. Therapy was given for up to 2 years, as long as there is no disease progression or unacceptable side effects. The primary objective of the study is to determine the ORR, which includes complete and partial responses (CR+PR). Secondary objectives include evaluating the safety of the combination, as well as assessing progression-free survival (PFS), duration of response (DOR), CR, and overall survival (OS). The study plan was to enroll a maximum of 106 pts, including a safety cohort of 6 pts. The study received funding from Bayer and conducted through NCI-CTEP (NCI Protocol #10193; NCT03484819). Results: Twelve pts who received at least one cycle of C-N were included in this analysis. Pt characteristics are illustrated in table 1. All enrolled pts had DLBCL histology. Only one patient received a prior autologous stem cell transplant. Interestingly 4/12 received prior chimeric antigen receptor T-cell therapy (CART). Of the 12 enrolled pts, seven were evaluated for response. The ORR was 25% (3/12) (95% CI: 5 - 57%), all CR. The median number of cycles received was 2.5 (range 1-24) with two pts receiving 23 and 24 cycles. Observed grade 3 and higher adverse events (AEs) were as follows: non-hematologic AEs in 10/12 (83.3%), while hematologic AEs were seen in 5/12 (41.7%) pts. A relatively higher incidence of cardiac events (4/12) were noted including one cardiac arrest after one cycle of therapy, and four atrial fibrillation events, all grade 3, but only two were deemed possibly attributed to therapy. The cardiac arrest was deemed unrelated to therapy. Conclusions: C-N combination had modest clinical activity in pts with R/R DLBCL with some prolonged responses. However, due to the relatively high number of cardiac events and the changing therapeutic landscape with recent approvals, a decision was made to halt the study. These findings likely reflect possibly older and sicker patient population. Biomarker studies for predictors of response are under consideration.

Systemic juvenile idiopathic arthritis: The Great Ormond Street Hospital experience (2005-2021).

Systemic juvenile idiopathic arthritis (sJIA) is a complex, systemic inflammatory disorder driven by both innate and adaptive immunity. Improved understanding of sJIA pathophysiology has led to recent therapeutic advances including a growing evidence base for the earlier use of IL-1 or IL-6 blockade as first-line treatment. We conducted a retrospective case notes review of patients diagnosed with sJIA over a 16-year period (October 2005-October 2021) at Great Ormond Street Hospital for Children. We describe the clinical presentation, therapeutic interventions, complications, and remission rates at different timepoints over the disease course. We examined our data, which spanned a period of changing therapeutic landscape, to try and identify potential therapeutic signals in patients who received biologic treatment early in the disease course compared to those who did not. A total of 76-children (female n = 40, 53%) were diagnosed with sJIA, median age 4.5 years (range 0.6-14.1); 36% (27/76) presented with suspected or confirmed macrophage activation syndrome. A biologic disease-modifying anti-rheumatic drug (bDMARD) alone was commenced as first-line treatment in 28% (n = 21/76) of the cohort; however, at last review, 84% (n = 64/76) had received treatment with a bDMARD. Clinically inactive disease (CID) was achieved by 88% (n = 67/76) of the cohort at last review; however, only 32% (24/76) achieved treatment-free CID. At 1-year follow-up, CID was achieved in a significantly greater proportion of children who received treatment with a bDMARD within 3 months of diagnosis compared to those who did not (90% vs. 53%, p = 0.002). Based on an ever-increasing evidence base for the earlier use of bDMARD in sJIA and our experience of the largest UK single-centre case series described to date, we now propose a new therapeutic pathway for children diagnosed with sJIA in the UK based on early use of bDMARDs. Reappraisal of the current National Health Service commissioning pathway for sJIA is now urgently required.

Myasthenia in adults, children, and adolescents: what's new?

Therapy of myasthenia gravis (MG) is increasingly oriented to the patient's antibody status. In addition to symptomatic therapy, steroids, classic long-term immunosuppressive therapies and thymectomy are regularly used. In recent years, new therapeutic approaches have been developed that particularly benefit acetylcholine receptor (AChR) antibody (Abs) positive patients with highly active disease. While the C5 complement inhibitor eculizumab was reserved for treatment-refractory generalized courses of AChR-Abs positive MG, two new drugs, the neonatal Fc receptor inhibitor efgartigimod and the more advanced C5 complement inhibitor ravulizumab, have recently been approved as add-on therapy for AChR-Abs positive generalized MG (gMG). In highly active courses of MG with Abs against the muscle-specific receptor tyrosine kinase (MuSK), the use of rituximab should be considered early in the course of the disease. The efficacy of the new drugs in children and adolescents with juvenile MG (JMG) is currently being tested in clinical trials. The new guideline recommends the use of modern immunomodulators based on astep-by-step approach depending on disease activity. With the German Myasthenia Register (MyaReg), the changing therapeutic landscape and quality of life of patients with myasthenic syndromes can be assessed, thus providing real-world data on the care of MG patients. Despite treatment based on the previous guideline, many MG patients suffer considerable impairment to their quality of life. With the new immunomodulators, there is the possibility of early intensified immunotherapy, which, in contrast to long-term immunosuppressants, can lead to arapid improvement in the course of the disease.

Impact of pre-existing anemia and/or packed red blood cell transfusion prior to Radium-223 administration on oncologic outcomes.

67 Background: Radium-223 (Ra-223), a targeted alpha-emitting radiopharmaceutical approved for the treatment of metastatic prostate cancer (mPC), can cause myelosuppression. In the ALSYMPCA trial 30% of patients developed cytopenias, including 13% with grade 3/4 anemia. Therefore, it is recommended that only men with a hemoglobin ≥10 g/dL, platelet count ≥100,000/mm3, and ANC ≥1,500/mm3 be considered for Ra-223. Since the FDA approval of Ra-223 in 2013, several new treatments have been approved for men with mPC. With the changing therapeutic landscape, we anticipate more patients (pts) will have preexisting cytopenia prior to Ra-223 consideration. Hence, clinicians are increasingly likely to face the dilemma of whether it is safe and efficacious to administer Ra-223 in the setting of Hgb ≤10 with/without RBC transfusion support. Methods: We retrospectively identified pts with mPC treated with Ra-223, including a subset of men with Hgb <10g/dl at the Medical College of Wisconsin and Tulane Cancer Center from 2014 – 2019. Clinical data including demographics, prior cancer treatments, laboratory data, blood product transfusion data, and oncologic outcomes were collected. Survival was estimated using Kaplan-Meier method and statistical analysis was conducted using student’s t-test. Results: Sixty-two pts were identified. Median age at the time of Ra-223 was 75.3 years. Of these, nearly 20% (n=12) had a Hgb <10 g/dL and/or received RBC transfusions to meet “eligibility criteria” prior to beginning Ra-223 treatments. Compared to men who had Hgb >10g/dL, men with Hgb <10g/dL required more RBC transfusions both during and after Ra-223 treatment and had significantly worse oncologic outcomes. No patients experienced treatment delays of more than 1 week. There were no significant differences in the median number of treatments prior to Ra-223, median number of Ra-223 treatments received, platelet count nadir, or ANC nadir. Conclusions: Pre-existing Hgb < 10 g/dl and/or RBC transfusions prior to Ra-223 therapy is associated with worse oncologic outcomes in mPC, suggesting that the benefit of Ra-223 is limited in this subset. A larger sample size is needed to further validate our findings. Multivariable analysis is planned. [Table: see text]

Improving experience of medical abortion at home in a changing therapeutic, technological and regulatory landscape: a realist review

ObjectiveTo inform UK service development to support medical abortion at home, appropriate for person and context.DesignRealist reviewSetting/participantsPeer-reviewed literature from 1 January 2000 to 9 December 2021, describing interventions or models...

A call to action for anticoagulation stewardship

A call to action for anticoagulation stewardship

The changing therapeutic landscape of spinal muscular atrophy.

The clinical approach to spinal muscular atrophy (SMA) has changed, and the condition is now a treatable neurodegenerative disease, with treated infants and children experiencing gains in motor function and significant increases in survival. Consequently, it is important for primary care physicians to be aware oftheir role in both detection and community support of people with SMAand their families. The aim of this article is to discuss the pertinent features of SMA relevant to the primary physician including presenting features, symptoms and signs, prognosis, treatment options and genetic carrier screening for the condition. SMA is a neuromuscular disorder characterised by progressive proximal muscle weakness. If SMA is suspected, patients should be referred immediately, particularly hypotonic infants and children not obtaining, or falling behind, the motor milestones of their peers. Early recognition and prompt intervention are associated with greater clinical efficacy of genetic disease-modifying therapies. National guidelines recommend carrier screening is offered to all who are considering pregnancy or are in early pregnancy.

Will the changing therapeutic landscape meet the needs of patients with sickle cell disease?

Will the changing therapeutic landscape meet the needs of patients with sickle cell disease?

Topography and scale in a community-driven maternal and child health program in Eastern Indonesia

In 2007, the Indonesian government introduced Generasi, a community-driven development program to address village priorities such as reducing poverty, maternal mortality, and child mortality. When describing Generasi’s biggest challenges, program facilitators on the eastern Indonesian island of Flores used a geographic vocabulary of fields (medan, lapangan) and topography (topografi) that evokes the demands of supervising Generasi’s implementation across dozens of mountain villages with poor infrastructure. But their geographic language also extends metaphorically to the enduring problems of scale and governance. I analyze these discourses of topography and field in relation to the changing therapeutic landscape of maternal and child health services in the Manggarai highlands of western Flores, then follow Generasi’s scalar scaffolding from the meetings and clinics in villages, to the technocratic policy work in Jakarta, and to the academic spaces of Auckland and Cambridge.

The German Hemophilia Registry: Growing with Its Tasks.

Hemophilia is a rare heredity bleeding disorder that requires treatment for life. While few therapeutic options were available in the past, multiple recent breakthroughs have fundamentally altered and diversified hemophilia therapy, with even more new therapeutic options forthcoming. These changes are mirrored by significant regulatory and legal changes, which have redefined the role of hemophilia registries in the European Union (EU). This dual paradigm shift poses new regulatory, scientific but also structural requirements for hemophilia registries. The aim of this manuscript is to enumerate these significant challenges and to demonstrate their incorporation into the redesign of the German Hemophilia Registry (Deutsches Hämophilieregister, dhr). To identify the spectrum of hemophilia therapies and the degree of regulatory changes, a horizon screening was performed. Consequently, a core dataset for the dhr was defined by harmonization with regulatory guidelines as well as other hemophilia registries and by heeding the needs of different stakeholders (patients, clinicians, regulators, and scientists). Based on this information, a new registry structure was established, which is optimized for capturing data on new and established hemophilia therapies in a changing therapeutic and regulatory landscape

The changing therapeutic landscape, burden of disease, and unmet needs in patients with cutaneous T-cell lymphoma.

SummaryCutaneous T‐cell lymphomas (CTCLs) have a chronic, relapsing course, and the most common subtypes are mycosis fungoides and Sézary syndrome. The disease causes visible skin alterations and can also cause alopecia, pruritus and pain, all of which can impact patients’ health‐related quality of life (HRQoL). The goal of treatment is to reduce symptoms and prevent disease progression. However, treatment recommendations are often based on low levels of evidence due to the lack of well‐designed randomised clinical trials and treatment guidelines, and approved drugs vary considerably across different countries and regions. Currently, available treatments rarely lead to durable remissions and eventually become less effective, meaning patients often require multiple therapy changes. Skin‐directed therapies (SDTs) are first‐line treatments for early‐stage CTCL, whereas systemic therapies may be needed for early‐stage disease that does not respond to SDT or for advanced‐stage disease. However, patients can experience significant side‐effects with these treatments or may be unable to tolerate them. Hence, there is an unmet need for effective therapies with good safety profiles for the treatment of early‐ and late‐stage CTCL. Here, we review current treatment guidelines, investigational and approved treatments, the impact of CTCL on patients’ HRQoL, and the treatment of pruritus.

Real-world patient-reported outcomes of women receiving initial endocrine-based therapy for HR+/HER2\u2212 advanced breast cancer in five European countries

BackgroundEndocrine therapy (ET)-based regimens are the mainstay of treatment for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) advanced breast cancer. With the introduction of new treatment classes, it is important to examine patient symptoms and health-related quality of life (HRQoL) at the start of this changing therapeutic landscape. This real-world study describes the patient-reported outcomes (PROs) of women with HR+/HER2− advanced breast cancer receiving ET-based regimens who were naïve to systemic treatment in the advanced setting across five European countries (EU5).MethodsData were collected between March and July 2017 from surveyed oncologists and their patients at a single time point using the multinational Adelphi Advanced Breast Cancer Disease Specific Programme™. Patients completed PRO questionnaires on HRQoL (EORTC QLQ-C30), pain severity and interference, and work and activity impairment. A multiple linear regression model explored factors associated with HRQoL.ResultsAcross EU5, 226 physicians provided data on 781 women with HR+/HER2− advanced breast cancer taking their first ET-based regimen for advanced disease, of whom 252 provided PRO data. This subset had a mean age of 67.1 years, 94% were postmenopausal, 89% were diagnosed with advanced breast cancer at initial presentation, 79% had stage IV disease (66% of these patients had bone metastases and 38% had visceral metastases, including 18% with liver metastases) and 77% were on endocrine-only therapy as their initial treatment for advanced disease. The mean EORTC QLQ-C30 global health score (50.9) was worse than the reference value for patients with advanced breast cancer (60.2). Fatigue, pain, and insomnia were the most severe symptoms, and mean functioning scores were also worse than reference values. “Worst pain” and “pain interference” were moderate/severe for 42 and 80% of patients. Mean activity impairment was 44%, and greater activity impairment was associated with poorer HRQoL.ConclusionsDespite receiving first-line ET-based regimens for advanced disease, these women had a poor HRQoL and high levels of symptoms, pain, pain interference and activity impairment. New treatments that maintain a stable disease state and reduce activity impairment may have a positive effect on the HRQoL of those living with advanced breast cancer.

Non-interventional LUME-BioNIS study of nintedanib plus docetaxel after chemotherapy in adenocarcinoma non-small cell lung cancer: A subgroup analysis in patients with prior immunotherapy

ObjectivesTo evaluate the effectiveness and safety of nintedanib plus docetaxel in patients with advanced adenocarcinoma non-small cell lung cancer (NSCLC) previously treated with both chemo- and immunotherapy. Materials and methodsLUME-BioNIS is a European, prospective, multicenter, non-interventional study of patients with advanced adenocarcinoma NSCLC, who initiated nintedanib plus docetaxel after first-line chemotherapy in routine practice according to the approved nintedanib EU label. The primary objective is to explore whether molecular biomarkers can predict overall survival (OS). Information on clinical or radiologic progression and death, and adverse drug reactions (ADRs)/fatal adverse events (AEs) was collected during follow-up. Here, we report a subgroup analysis evaluating outcomes in immunotherapy-pretreated patients. ResultsOf 260 enrolled patients, 67 (25.8%) had prior immunotherapy and were included in this subgroup analysis. Prior immunotherapy was administered in first-line in 20 patients (29.9%; combined with chemotherapy in 4 patients [6.0%]) and later-lines in 47 patients (70.1%), and most commonly comprised nivolumab (39 patients; 58.2%), atezolizumab (14 patients; 20.9%) and pembrolizumab (11 patients; 16.4%). Nintedanib plus docetaxel was given in second-line in 10 patients (14.9%) and in later-lines in 57 patients (85.1%). Median OS was 8.8 months (95% confidence interval [CI]: 7.0–11.5) and median progression-free survival (PFS) was 4.6 months (95% CI: 3.5–5.7). Among 55 patients with available data, rates of objective response and disease control were 18.2% and 78.2%, respectively. In 65 patients evaluable for safety, the most common on-treatment ADRs/AEs were malignant neoplasm progression (19 patients; 29.2%), diarrhea (21 patients; 32.3%) and nausea (10 patients; 15.4%). ConclusionsUsed according to the approved nintedanib label in routine practice, nintedanib plus docetaxel demonstrated clinical effectiveness, with no unexpected safety findings, in patients with prior chemotherapy and first- or later-line immunotherapy. These data add to the real-world evidence that can inform clinical decisions in the changing therapeutic landscape.

Nintedanib (N) + docetaxel (D) after immunotherapy in adenocarcinoma non-small cell lung cancer (NSCLC): First results from the non-interventional LUME-BioNIS study

Abstract Background N is an oral triple angiokinase inhibitor approved in 61 countries for use with D to treat locally advanced, metastatic or locally recurrent adenocarcinoma NSCLC after first-line chemotherapy (CT). Several immunotherapies are also now approved in various indications in advanced NSCLC, but limited data are available regarding outcomes with N + D after immunotherapy treatment. Methods LUME-BioNIS is a European, prospective, multicentre, non-interventional study of patients (pts) with advanced adenocarcinoma NSCLC who initiated N + D after first-line CT in routine practice according to the approved N EU label. Information on dates of progression (based on clinical assessment or Response Evaluation Criteria in Solid Tumors) and death and adverse events (AEs) was collected via an electronic case report form. The primary endpoint was overall survival (OS). A subgroup analysis was conducted to evaluate outcomes in pts with prior immunotherapy. Results In the 67 pts with prior immunotherapy, median age was 63 years and 27 pts (40.3%) were female. Prior immunotherapy was given in first line in 20 pts (29.9%) and in later lines in 47 pts (70.1%). The most common immunotherapies were nivolumab (39 pts; 58.2%), atezolizumab (13 pts; 19.4%) and pembrolizumab (11 pts; 16.4%). N + D was given in second line in 10 pts (14.9%) and in later lines in 57 pts (85.1%). Median progression-free survival (PFS) was 4.6 months (95% confidence interval [CI]: 3.5–5.7) and median OS was 8.8 months (95% CI: 7.0–11.5). In 65 pts evaluable for safety, the most common on-treatment AEs were malignant neoplasm progression (18 pts; 27.7%), diarrhoea (21 pts; 32.3%), nausea (10 pts; 15.4%) and vomiting (7 pts; 10.8%). Conclusion Used according to the approved N label in routine practice, N + D showed clinically relevant effectiveness, with no unexpected safety findings, in pts with prior immunotherapy and CT. The observed median PFS and OS of 4.6 and 8.8 months, respectively, are encouraging, given the use of N + D in third or later lines in 85.1% of pts. These data add to the real-world evidence that can inform clinical decision-making in the changing therapeutic landscape. Clinical trial identification NCT02671422. Editorial acknowledgement Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Mark Dyson, DPhil (Berlin, Germany) on behalf of Syneos Health (London, UK). Legal entity responsible for the study Boehringer Ingelheim Pharma GmbH & Co. KG. Funding Boehringer Ingelheim Pharma GmbH & Co. KG. Disclosure M. Reck: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: F. Hoffmann-La Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Celgene. K. Syrigos: Honoraria (self), Advisory / Consultancy: F. Hoffmann-La Roche; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: MSD. S. Zochbauer-Muller: Advisory / Consultancy, fees for participation in the LUME-BioNIS study: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony, fees for advisory boards and lectures: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony, fees for advisory boards and lectures: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, fees for advisory boards and lectures: Bristol-Myers Squibb; Advisory / Consultancy, fees for advisory boards: Roche; Advisory / Consultancy, fees for advisory boards: AstraZeneca; Advisory / Consultancy, fees for advisory boards: Takeda; Speaker Bureau / Expert testimony, fees for lectures: Pfizer. H. Buchner: Research grant / Funding (self), former employee; received financial support for performing analyses during the conduct of the study: Boehringer Ingelheim Pharma GmbH & Co. KG. T. Kitzing: Full / Part-time employment, current employee of Boehringer Ingelheim Pharma GmbH & Co. KG: Boehringer Ingelheim Pharma GmbH & Co. KG. K.M. Kerr: Advisory / Consultancy, personal fees from Boehringer Ingelheim during the conduct of the LUME-BioNIS study: Boehringer Ingelheim. All other authors have declared no conflicts of interest.

The changing therapeutic landscape of head and neck cancer.

Head and neck cancers are a heterogeneous collection of malignancies of the upper aerodigestive tract, salivary glands and thyroid. In this Review, we primarily focus on the changing therapeutic landscape of head and neck squamous cell carcinomas (HNSCCs) that can arise in the oral cavity, oropharynx, hypopharynx and larynx. We highlight developments in surgical and non-surgical therapies (mainly involving the combination of radiotherapy and chemotherapy), outlining how these treatments are being used in the current era of widespread testing for the presence of human papillomavirus infection in patients with HNSCC. Finally, we describe the clinical trials that led to the approval of the first immunotherapeutic agents for HNSCC, and discuss the development of strategies to decrease the toxicity of different treatment modalities.

Duchenne Muscular Dystrophy Newborn Screening, a Case Study for Examining Ethical and Legal Issues for Pilots for Emerging Disorders: Considerations and Recommendations.

Duchenne muscular dystrophy (DMD/Duchenne) is one of the ten most severe and common pediatric genetic diseases and affects an estimated 1 in every 5000 male births. While Duchenne is a 100% fatal disease, the clinical community has demonstrated that immediate identification and early clinical interventions can add years, even decades to an individual’s life span. In anticipation of the changing therapeutic landscape for the Duchenne community, Parent Project Muscular Dystrophy established a newborn screening (NBS) initiative. This initiative included a Bioethics and Legal Issues Workgroup to consider the bioethics and legal issues of NBS for Duchenne. The workgroup’s discussion focused only on Duchenne NBS and met through conference calls over a one-year period of time seeking consensus on various identified issues. This article reports on the findings and recommendations from that workgroup.

Three‐Dimensional Stereophotogrammetry: A Novel Method in Volumetric Measurement of Infantile Hemangioma

Accurate and objective measurement of volume changes in infantile hemangiomas (IHs) is essential in routine clinical practice and clinical studies, particularly in the changing therapeutic landscape after the discovery of propranolol. Several bedside techniques for volume measurement have been described in the literature, but an objective method of measurement of this variable, dynamic vascular tumor is lacking. Three-dimensional (3D) phototechnology with data analysis is an up-and-coming technique in the objective measurement of facial volume changes. In this pilot study, the usability and clinical relevance of two methods of 3D stereophotogrammetry in the volume measurement of IH were explored.

The changing therapeutic landscape for hepatitis C

The next decade will be a crucial period in the public health response to hepatitis C virus (HCV) infection. The rapid development of direct-acting antiviral therapy for HCV infection has brought considerable optimism to the HCV sector, with the realistic hope that therapeutic intervention will soon be more effective and offer shorter treatment duration. The initial phase of combination pegylated interferon, ribavirin and a protease inhibitor will be associated with increased toxicity and complexity of therapeutic management but, over the course of the decade, strategies including interferon-free combination direct-acting antiviral regimens with enhanced tolerability and simplified dosing schedules and monitoring protocols will emerge.