Adalimumab (ADL, Humira
®
, reference product), an anti-TNF-α biologic, has transformed the treatment of chronic, immune-mediated inflammatory diseases. However, the high cost of ADL therapy has ...driven the development of more affordable ADL biosimilars, agents with no clinically meaningful differences from the reference product. This review summarizes the product attributes of reference ADL and the nine ADL biosimilars approved and available in the USA in relation to patient experience of injection-site pain (ISP). Product formulation, delivery volume and device features (e.g., type and needle gauge size) influence patient experience of ISP with potential clinical consequences. Citrate-free formulations generally cause less ISP; injection volumes of > 1.5 ml may be associated with increased ISP. Reference ADL and all ADL biosimilars offer a citrate-free formulation, and reference ADL and four ADL biosimilars offer a high-concentration solution that allows a smaller injection volume. All available ADL products are injected subcutaneously using either a pre-filled pen (PFP) or pre-filled syringe (PFS). Patients prefer the PFP, but the PFS permits better control over the speed and duration of injection. Smaller (29-gauge) needle outer diameter is associated with less ISP; reference ADL and seven ADL biosimilars offer a device with a 29-gauge needle. In the USA, an approved biosimilar can be designated “interchangeable,” allowing pharmacy-level substitution, where state law permits. In the USA, two ADL biosimilars have received interchangeability designation; others are seeking interchangeability designation from the Food and Drug Administration (
n
= 2), are being evaluated in clinical studies to support interchangeability (
n
= 2), or do not have/are not seeking interchangeability designation (
n
= 3). Product-related attributes influence patient experience of ISP caused by subcutaneous ADL injection. Reference ADL and ADL biosimilar products differ in their attributes, so discussion with patients about treatment options is essential to optimize adherence and outcomes.
This status article describes current state-of-the-art radiotherapy for lymphomas and new emerging techniques. Current state-of-the-art radiotherapy is sophisticated, individualised, CT-based, ...intensity-modulated treatment, using PET/CT to define the target. The concept of involved site radiotherapy should be used, delineating the target using the exact same principles as for solid tumours. The optimal treatment delivery includes motion management and online treatment verification systems, which reduce intra- and interfractional anatomical variation. Emerging radiotherapy techniques in lymphomas include adaptive radiotherapy in MR- and CT-based treatment systems and proton therapy. The next generation linear accelerators have the capability to deliver adaptive treatment and allow relatively quick online adaptation to the daily variations of the anatomy. The computer systems use machine leaning to facilitate rapid automatic contouring of the target and organs-at-risk. Moreover, emerging MR-based planning and treatment facilities allow target definition directly from MR scans and allow intra-fractional tracking of structures recognisable on MR. Proton facilities are now being widely implemented. The benefits of proton therapy are due to the physical properties of protons, which in many cases allow sparing of normal tissue. The variety of techniques in modern radiotherapy means that the radiation oncologist must be able to choose the right technique for each patient. The choice is mainly based on experience and standard protocols, but new systems calculating risks for the patients with a specific treatment plan and also systems integrating clinical factors and risk factors into the planning process itself are emerging.
Radiotherapy (RT) can be curative in patients with localized follicular lymphoma (FL), with historical series showing a 10-year disease-free survival of 40 to 50%. As 18F-fluorodeoxyglucose (18F-FDG) ...positron emission tomography with computerized tomography (PET-CT) upstages 10 to 60% of patients compared to CT, we sought to evaluate outcomes in patients staged by PET-CT, to determine if more accurate staging leads to better patient selection and results. We conducted a multicenter retrospective study under the direction of the International Lymphoma Radiation Oncology Group (ILROG). Inclusion criteria were: RT alone for untreated stage I to II FL (grade 1-3A) with dose equivalent ≥24 Gy, staged by PET-CT, age ≥18 years, and follow-up ≥3 months. End points were freedom from progression (FFP), local control, and overall survival (OS). A total of 512 patients treated between 2000 and 2017 at 16 centers were eligible for analysis; median age was 58 years (range, 20-90); 410 patients (80.1%) had stage I disease; median RT dose was 30 Gy (24-52); and median follow-up was 52 months (3.2-174.6). Five-year FFP and OS were 68.9% and 95.7%. For stage I, FFP was 74.1% vs 49.1% for stage II (P < .0001). Eight patients relapsed in-field (1.6%). Four had marginal recurrences (0.8%) resulting in local control rate of 97.6%. On multivariable analysis, stage II (hazard ratio HR, 2.11; 95% confidence interval CI, 1.44-3.10) and BCL2 expression (HR, 1.62; 95% CI, 1.07-2.47) were significantly associated with less favorable FFP. Outcome after RT in PET-CT staged patients appears to be better than in earlier series, particularly in stage I disease, suggesting that the curative potential of RT for truly localized FL has been underestimated.
•Outcomes after RT for stage I and localized stage II FL after PET-CT staging are better than those in historical series.•More than two-thirds of patients remain in remission at 5 years, and most relapses occur at distant sites.
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Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon histologic variant, and the optimal treatment of stage I-II NLPHL is undefined. We conducted a multicenter retrospective study ...including patients ≥16 years of age with stage I-II NLPHL diagnosed from 1995 through 2018 who underwent all forms of management, including radiotherapy (RT), combined modality therapy (CMT; RT+chemotherapy CT), CT, observation after excision, rituximab and RT, and single-agent rituximab. End points were progression-free survival (PFS), freedom from transformation, and overall survival (OS) without statistical comparison between management groups. We identified 559 patients with median age of 39 years: 72.3% were men, and 54.9% had stage I disease. Median follow-up was 5.5 years (interquartile range, 3.1-10.1). Five-year PFS and OS in the entire cohort were 87.1% and 98.3%, respectively. Primary management was RT alone (n = 257; 46.0%), CMT (n = 184; 32.9%), CT alone (n = 47; 8.4%), observation (n = 37; 6.6%), rituximab and RT (n = 19; 3.4%), and rituximab alone (n = 15; 2.7%). The 5-year PFS rates were 91.1% after RT, 90.5% after CMT, 77.8% after CT, 73.5% after observation, 80.8% after rituximab and RT, and 38.5% after rituximab alone. In the RT cohort, but not the CMT cohort, variant immunoarchitectural pattern and number of sites >2 were associated with worse PFS (P < .05). Overall, 21 patients (3.8%) developed large-cell transformation, with a significantly higher transformation rate in those with variant immunoarchitectural pattern (P = .049) and number of involved sites >2 (P = .0006). OS for patients with stage I-II NLPHL was excellent after all treatments.
•Upfront treatment of stage I-II NLPHL with RT/CMT is associated with excellent PFS.•Acknowledging the excellent prognosis, the risk of late effects and potential for transformation should inform management decisions.
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•There is little published data on the use of DIBH and Butterfly volumetric arc therapy for the treatment of mediastinal lymphoma.•Experience of a 5 year service was analysed looking into ...immobilisaiton, IGRT, patient compliance, and completion of the patient pathway without interruption.•It is noted that a successful service has been implemented with minimal disruption to the patient pathway and optimal treatment delivered.
Deep inspiration breath-hold (DIBH) is an advanced radiotherapy technique that has been shown to have dosimetric benefits in the treatment of patients with mediastinal lymphoma. Whilst there is much published data on the use of DIBH in breast radiotherapy, reports on the use of the technique in mediastinal lymphoma patients remain limited. As the first NHS centre in the UK to implement DIBH in this pt group, we have evaluated our experience and success in using this technique over a 5 year period.
•DIBH, Butterfly volumetric arc therapy and advanced IGRT were introducedin a three step implementation process by an experienced radiotherapy department.•Provided is a reflection of the lessons ...learned by this implementation and the impact across the patient pathway, from pre-treatment through to treatment delivery.•It is shown that key training and education are vital parts of the implementation process, and the deparmtnet benefitted from a 3-step process, as well as the necessity for 3D advanced imaging.
Deep inspiration breath-hold, butterfly volumetric modulated arc therapy and daily imaging techniques for mediastinal lymphoma patients have been introduced in a single department. Whilst introducing these techniques, there were many practical lessons to be learned across the patient pathway, from pre-treatment through to treatment delivery.Therapeutic radiographers were key members of the multi-disciplinary team implementing these techniques. This work reflects on the experience of introducing these advanced techniques for mediastinal lymphoma patients and the lessons learnt.
Micro-credentials (MCs) and digital badges (DBs) have gained popularity in recent years as a means to supplement traditional degrees and certifications. MCs and DBs can play a significant role in ...supporting student-centered learning by offering personalized and flexible learning pathways, emphasizing real-world relevance and practical skills, and fostering a culture of continuous learning and growth. However, barriers currently exist within health professions education, including pharmacy education, that could limit the full adoption and implementation of MCs and DBs. Research on the use of MCs and DBs in Doctor of Pharmacy degree programs is sparse. In this integrative review, literature on the use of MCs and DBs in health professions education is reviewed, and perspectives on the benefits, issues, and potential future uses within Doctor of Pharmacy degree programs are presented.
We previously reported that ∼30% of patients with localized follicular lymphoma (FL) staged by
F-fluorodeoxyglucose positron emission tomography-computed tomography receiving primary radiation ...therapy (RT) will relapse within 5 years. We sought to report outcomes for those who relapsed.
We conducted a multicenter, retrospective study of patients aged ≥18 years who received RT ≥ 24 Gy for stage I to II, grade 1 to 3A FL, staged with
F-fluorodeoxyglucose (
F-FDG) positron emission tomography-computed tomography. Observation was defined as >6 months without treatment from relapse. Overall survival (OS) and freedom from progression (FFP) were estimated with Kaplan-Meier analysis and univariable and multivariable analyses with Cox regression.
Of 512 patients with median follow-up of 52 months, 149 (29.1%) developed recurrent lymphoma at a median of 23 months (range, 1-143) after primary RT. Median follow-up was 33 months after relapse. Three-year OS was 91.4% after recurrence. OS was significantly worse for those with relapse ≤12 months from date of diagnosis versus all others-88.7% versus 97.6%, respectively (P = .01)-and remained significantly worse on multivariable analyses (follicular lymphoma international prognostic index-adjusted hazard ratio, 3.61; P = .009). Histology at relapse included 93 indolent (grade 1-3A), 3 FL grade 3B/not otherwise specified, and 18 diffuse large B-cell lymphoma; 35 patients did not undergo biopsy. Of those with follow-up ≥3 months who underwent biopsy (n = 74) or had presumed (n = 23) indolent recurrence, 58 patients (59.8%) were observed, 19 (19.6%) had systemic therapy, 16 (16.5%) had RT, and 4 (4.1%) had systemic therapy + RT. For patients with indolent recurrences that were observed, 3-year FFP or freedom from treatment was 56.6% (median, 48 months). For all patients with biopsied/presumed indolent recurrence receiving salvage treatment (n = 59, including 20 initially observed) 3-year FFP was 73.9%.
Prognosis for patients with relapsed FL after primary radiation therapy is excellent, supporting the role of primary radiation in the management of early stage disease. Patients with localized FL treated with primary RT who experience early relapse (<12 months) have inferior survival compared with those with longer disease-free interval.
Researchers have indicated that female soccer players may be at greater risk of concussion compared with their male counterparts. Soccer headgear is marketed for reducing head acceleration and risk ...of concussion.
To determine the effect of sex and soccer headgear on head impact kinematics and dynamic stabilization during soccer heading.
Cross-sectional design.
Research laboratory.
Forty-four college-aged soccer players (29 women, 15 men).
Using a head impact model, participants performed 4 soccer headers under 3 headgear conditions (control, Head Blast Soccer Band, and Full90 Select Performance Headguard).
Dependent variables assessed before soccer heading were head-neck anthropometrics and isometric neck muscle strength, and those assessed during soccer headers were resultant linear head acceleration, Head Injury Criteria (HIC(36)), and superficial neck muscle electromyography. Statistical analyses included multivariate and univariate analyses of variance with repeated measures, independent-samples t tests, appropriate follow-up analyses of variance and post hoc t tests, and Pearson product moment correlations (alpha = .05).
Head acceleration in women was 32% and 44% greater than in men when wearing the Head Blast (21.5 g versus 16.3 g) and Full90 Select (21.8 g versus 15.2 g), respectively (P < .05). Compared with men, women exhibited 10% greater head accelerations (20.2 g versus 18.2 g) during the control condition (P = .164).
Female soccer players exhibited greater head accelerations than their male counterparts when wearing headgear. Our results are important clinically because they indicate that soccer headgear may not be an appropriate head injury prevention tool for all athletes.
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