Design of the SPIROMICS Study of Early COPD Progression: SOURCE Study.

The biological mechanisms leading some tobacco-exposed individuals to develop early-stage chronic obstructive pulmonary disease (COPD) are poorly understood. This knowledge gap hampers development of disease-modifying agents for this prevalent condition. Accord-ingly, with National Heart, Lung and Blood Institute support, we initiated the SPIROMICS Study of Early COPD Progression (SOURCE), a multicenter observational cohort study of younger individuals with a history of cigarette smoking and thus at-risk for, or with, early-stage COPD. Our overall objectives are to identify those who will develop COPD earlier in life, characterize them thoroughly, and by contrasting them to those not developing COPD, define mechanisms of disease progression. SOURCE utilizes the established SPIROMICS clinical network. Its goal is to enroll n=649 participants, ages 30-55 years, all races/ethnicities, with ≥10 pack-years cigarette smoking, in either Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups 0-2 or with Preserved Ratio Impaired Spirometry (PRISm); and an additional n=40 never-smoker controls. Participants undergo baseline and three-year follow-up visits, each including high-resolution computed tomography; respiratory oscillometry and spirometry (pre- and post-bronchodilator administration), exhaled breath condensate (baseline only); and extensive biospecimen collection, including sputum induction. Symptoms, interim healthcare utilization, and exacerbations are captured every six months via follow-up phone calls. An embedded bronchoscopy sub-study involving n=100 participants (including all never-smokers) will allow collection of lower airway samples for genetic, epigenetic, genomic, immunological, microbiome, mucin analyses, and basal cell culture. SOURCE should provide novel insights into the natural history of lung disease in younger individuals with a smoking history, and its biological basis.

Commercial suture passer improves efficiency and ease of use versus conventional needle in minimally invasive thoracolumbar fascia closure: a cadaveric analysis.

Background: Low-profile suture passers have been introduced to facilitate thoracolumbar fascia closure in minimally invasive spine (MIS) surgery. The purpose of this study was to evaluate the closure time of a modern suture passer to a conventional curved need for MIS fascia closure in a cadaveric model. Methods: Six clinicians specializing in orthopedic spine surgery were recruited for the study and randomly assigned 1 cadaveric torso. Subcutaneous tissue was resected at L4-L5, replicating MIS surgery, followed by placement of a 60×18-mm or 100×18-mm tubular retractor for access. Clinicians were required to close the fascia with three unknotted, simple interrupted sutures using a swaged curved needle or suture passer (Spine Scorpion™, Arthrex, Inc., Naples, FL). The completion time was recorded, starting immediately before suturing and ending after the last pass. A time cutoff of 10 min was implemented in consideration of reasonable operating room time, and the number of achieved suture passes (of 6) were recorded. Clinicians were asked to qualitatively grade ease of use in relation to prior fascial closure experience per a 0-5 scale, where 0 is impossible and 5 is easiest. Results: The mean change in fascial closure completion time (Δ) was significantly reduced with the Spine Scorpion compared to the curved needle with the 60×18-mm retractor (Δ=5.80 min; 95% CI, 2.92-8.67 min; p=.004) and 100 × 18-mm retractor (Δ=5.28 min; 95% CI, 2.76-7.80 min; p=.003). Full closure was achieved within the time limit for all trials of the Spine Scorpion, while the standard needle achieved full closure in 67% (4 of 6) and 50% (3 of 6) of trials with the 60 × 18-mm and 100×18-mm retractors, respectively. Median ease-of-use scores with the 60×18-mm and 100×18-mm retractors, respectively, were 4.5 (range, 4-5) and 4.5 (range, 3-5) for the Spine Scorpion, and both 1.0 (range, 1-2) for the curved needle. Conclusion: Results from this laboratory investigation using a suture passer for thoracolumbar fascia closure show a significant reduction in closure time and completion of the procedure compared to a conventional curved needle.

PRECISE: Preoperative Radiotherapy to Elicit Critical Immune Stimulating Effects - A Phase II Clinical Trial.

PURPOSE: Radiotherapy is an under-investigated tool for priming the immune system in intact human breast cancers. We sought here to investigate if a preoperative radiotherapy boost delivered was associated with a significant change in tumor infiltrating lymphocytes in the tumor in estrogen receptor positive, HER2Neu non-amplified breast cancers. METHODS AND MATERIALS: 20 patients were enrolled in a phase II clinical trial and received either 7.5Gy x 1 fraction or 2Gy x 5 fractions, completed 6-8 days prior to surgery. Percent stromal tumor infiltrating lymphocytes (TIL) were evaluated on hematoxylin and eosin-stained samples. Short-term safety was assessed based on time to surgery, toxicities, and cosmesis up to 6 months following boost. RESULTS: Stromal TIL increased 6-8 days following completion of boost radiotherapy (median 3.0 (IQR 1.0-6.5) prior to radiotherapy vs. median 5.0 (IQR 1.5-8.0) post radiotherapy, p=0.0037. Zero grade ≥ 3 toxicities up to 6 months following boost were experienced. 94% (16/17) patients with 6 month follow-up cosmetic assessment following breast conservation had good-excellent cosmesis by physician assessment. CONCLUSION: In this phase II trial, preoperative radiotherapy boost resulted in a short-term increase in stromal TIL with minimal toxicities. Preoperative breast radiotherapy appears to be safe and may be a feasible means for priming the tumor microenvironment.

Development of an intervention for patients following an anterior cruciate ligament rupture: an online nominal group technique consensus study.

OBJECTIVES: (1) To develop an intervention for to support patients diagnosed with an anterior cruciate ligament (ACL) rupture with decision-making regarding treatment. (2) To define evidence-based recommendations for the treatment of patients following an ACL rupture. DESIGN: Nominal group technique consensus study. SETTING: Online meetings with patients and key stakeholders working and receiving treatment in the National Health Service, UK. PARTICIPANTS: Consensus meetings composed of eight voting participants and five non-voting facilitators. Voting participants included five clinicians, one outpatient therapy manager and two patients with experience in an ACL rupture and reconstructive surgery. Non-voting facilitators supported group discussions and/or observed study procedures. This included a clinical academic expert, two methodology experts and two patient representatives. METHOD: Two online meetings were held. Pre-elicitation material was distributed ahead of the first meeting. Premeeting voting was conducted ahead of both meetings. A draft of the shared decision-making intervention and recommendations were shared ahead of the second meeting. Components were discussed and ranked for inclusion based on a 70% agreement threshold. RESULTS: The meetings led to the development of a shared decision-making intervention to support treatment decision-making following an ACL rupture. The intervention includes two components: (1) a patient information leaflet and key questions diagram and (2) option grid. The evidence-based recommendations encompass core components of treatment reaching the 70% threshold agreed by the group. The recommendations cover: (1) advice and education, (2) exercise guidance, (3) intervention delivery, (4) outcome measure use and (5) shared decision-making. CONCLUSION: This study has successfully developed a shared decision-making intervention to support ACL treatment decision-making, ready for testing in a future feasibility study. Evidence-based recommendations for the treatment of patients following ACL injury, ready for testing in a National Health Service (UK) setting, are also presented. TRIAL REGISTRATION NUMBER: NCT05529511.

Motion-Inclusive Treatment Planning to Assess Normal Tissue Dose for Central Lung Stereotactic Body Radiation Therapy.

Purpose: For lung stereotactic body radiation therapy, 4-dimensional computed tomography is often used to delineate target volumes, whereas organs at risk (OARs) are typically outlined on either average intensity projection (AIP) or midventilation (MidV = 30% phase) images. AIP has been widely adopted as it represents a true average, but image blurring often precludes accurate contouring of critical structures such as central airways. Here, we compare AIP versus MidV planning for centrally located tumors via respiratory motion-inclusive (RMI) plans to better evaluate dose delivered throughout the breathing cycle. Methods and Materials: Independently contoured and optimized AIP and MidV plans were created for 16 treatments and rigidly copied to each of the 10 breathing phase-specific computed tomography image sets. Resulting dose distributions were deformably registered back to the MidV image set (used as reference because of clearer depiction of anatomy compared with motion-blurred AIP) and averaged to create RMI plans. Doses to central OARs were compared between plans. Results: Mean absolute dose differences were low for all comparisons (range, 0.01-2.87 Gy); however, individual plans exhibited differences >20 Gy. Dose differences >5 Gy were observed most often for plan comparisons involving AIP-based plans (MidV vs AIP 23, AIP RMI vs AIP 12, MidV RMI vs AIP RMI 7, and MidV RMI vs MidV 8 times). Inclusion of respiratory motion reduced large dose differences. Standard OAR thresholds were exceeded up to 5 times for each plan comparison scenario and always involved proximal bronchial tree D4 cc tolerance dose. AIP-based contours were larger by, on average, 3% to 15%. Conclusions: Large dose differences were observed when plans with AIP-based contours were compared with MidV-based contours, indicating that observed dose differences were likely due to contoured volume differences rather than the effect of motion. Because of blurring with AIP images, MidV RMI-based planning may offer a more accurate method to determine dose to critical OARs in the presence of respiratory motion.

Residual Nodal Burden After Neoadjuvant Chemotherapy in cN1 Breast Cancer Patients with Positive Nodes at Targeted Axillary Dissection.

BACKGROUND: Targeted axillary dissection (TAD) facilitates nodal staging in cN1 breast cancer after neoadjuvant chemotherapy (NAC). Completion axillary node dissection (cALND) remains the standard of care for TAD-positive patients. This study investigated factors associated with additional positive nodes at cALND (cALND+) and the impact on the residual cancer burden (RCB). METHODS: Retrospective review of cN1 breast cancer patients treated with NAC and TAD was conducted from July 2013 to June 2023. The review defined cN1 status by ultrasound (US) and biopsy. Patient, tumor, and treatment characteristics were evaluated. Multivariate analysis was performed to identify factors associated with cALND+, and RCB was calculated. RESULTS: Of 902 patients who underwent TAD, 554 (61.4%) were TAD-positive. 457 underwent cALND, and 124 (27%) were cALND+ (average 4.1 additional +nodes). The cALND+ patients had larger primary tumors at diagnosis (4 vs 3.5 cm; p = 0.04), more than three suspicious nodes on initial US (30% vs 13%; p ≤ 0.0001), larger residual primary tumors on pathology (median, 3 vs 2.1 cm; p = 0.0004), and more positive TAD nodes (median, 2 vs 1; p ≤ 0.0001). In the multivariate analysis, the factors associated with cALND+ were more than three suspicious nodes on initial US (odds ratio [OR], 2.9; p ≤ 0.0001), more positive TAD nodes (OR, 1.1; p ≤ 0.0001), larger clipped node metastasis (OR, 1.1; p ≤ 0.0001), and larger residual tumor on pathology (OR, 1.1; p = 0.006). Of 65 cALND+ patients with RCB class I or II, 29 (45%) had an increase in RCB based on cALND. CONCLUSION: Of cN1 breast cancer patients treated with NAC who are TAD-positive, approximately 25% will have additional nodal disease on cALND. In these patients, positive cALND is associated with greater disease burden, which has potential implications for RCB status and prognosis.

The Importance of Digital Rectal Examination in Identifying Early-Onset Rectal Malignancies.

Colorectal cancer (CRC) is the second most diagnosed cancer and the second leading cause of cancer-related deaths in the United States. Rectal cancers, specifically, are the second most common cancer of the large intestine. Although once perceived as a disease of the elderly, the incidence of early-onset CRC (EO-CRC), classified as occurring in individuals less than 50 years old, has been paradoxically increasing. Although the incidence of rectal cancers has increased, the digital rectal exam (DRE) continues to be an underutilized physical exam maneuver when a patient presents with red-flag symptoms. Here, we present a case of a 38-year-old male from West Virginia who was referred to general surgery for complaints of rectal bleeding attributed to internal hemorrhoids. After undergoing a colonoscopy, the patient was found to have a rectal mass consistent with adenocarcinoma. We describe the importance of identifying red-flag signs to keep colorectal malignancy in the differential diagnosis in a young patient and highlight the importance of performing rectal exams to identify rectal cancers early to expedite treatment.

Clinical Outcomes for BRCA Pathogenic Variant Carriers With Breast Cancer Undergoing Breast Conservation.

Importance: Although most women with BRCA-associated breast cancer choose bilateral mastectomy, current guidelines support breast-conserving therapy as an option. As the indications for genetic testing expand and targeted therapies emerge, understanding the outcomes of breast-conserving therapy in the population of patients choosing breast conservation is important. Objective: To describe the clinical outcomes of women with BRCA-associated breast cancer who were treated with breast-conserving therapy, including the risks of ipsilateral and contralateral cancer events and bilateral mastectomy-free survival. Design, Setting, and Participants: This cohort study conducted at a single-institution academic national comprehensive cancer center included 172 women identified from a prospectively maintained database who had pathogenic BRCA1/2 variants and were treated with breast-conserving therapy from January 1, 1977, to December 31, 2021. Main Outcomes and Measures: Clinical and pathologic characteristics for patients with BRCA1 and BRCA2 were compared, and estimates of overall survival, bilateral mastectomy-free survival, distant disease-free survival, risk of ipsilateral breast cancer, and risk of contralateral cancer were computed. Results: The cohort included 172 women (mean [SD] age, 47.1 [11.7] years), with 42 (24.4%) receiving a diagnosis of breast cancer prior to 40 years of age. Compared with BRCA2 variant carriers (80 [46.5%]), women with BRCA1 variants (92 [53.5%]) were younger at breast cancer diagnosis and tended to have more advanced tumors, which were more likely to be hormone receptor negative and higher grade. At a median follow-up of 11.8 years (IQR, 5.7-18.2 years), estimates of 10-year survival and risk were: overall survival, 88.5% (95% CI, 83.1%-94.2%); bilateral mastectomy-free survival, 70.7% (95% CI, 63.3%-78.9%); risk of an ipsilateral breast cancer event, 12.2% (95% CI, 5.8%-18.2%); and risk of contralateral cancer, 21.3% (95% CI, 13.3%-28.6%). Risks continued to increase after 10 years of follow-up. Conclusions and Relevance: In this cohort study, although women with breast cancer and pathogenic BRCA1/2 variants treated with breast-conserving therapy had above-average risks of ipsilateral and contralateral breast cancer events, most did not have another cancer event and remained bilateral mastectomy free. These findings may be useful for informing patients with BRCA variants choosing breast conservation.

1H, 13C, and 15N resonance assignments of the La Motif of the human La-related protein 1.

Human La-related protein 1 (HsLARP1) is involved in post-transcriptional regulation of certain 5' terminal oligopyrimidine (5'TOP) mRNAs as well as other mRNAs and binds to both the 5'TOP motif and the 3'-poly(A) tail of certain mRNAs. HsLARP1 is heavily involved in cell proliferation, cell cycle defects, and cancer, where HsLARP1 is significantly upregulated in malignant cells and tissues. Like all LARPs, HsLARP1 contains a folded RNA binding domain, the La motif (LaM). Our current understanding of post-transcriptional regulation that emanates from the intricate molecular framework of HsLARP1 is currently limited to small snapshots, obfuscating our understanding of the full picture on HsLARP1 functionality in post-transcriptional events. Here, we present the nearly complete resonance assignment of the LaM of HsLARP1, providing a significant platform for future NMR spectroscopic studies.

Mindfulness in the Clinic Waiting Room May Decrease Pain: Results from Three Pilot Randomized Controlled Trials.

Introduction: Mindfulness interventions can improve a broad range of patient outcomes, but traditional mindfulness-based interventions are time and resource intensive. Emerging evidence indicates brief, single-session mindfulness interventions can also improve patient outcomes, and brief mindfulness interventions can be embedded into medical care pathways with minimal disruption. However, the direct impact of a brief mindfulness intervention on patients' pain while waiting in the clinic waiting room remains unexamined. Objective: A series of three, pilot, randomized controlled trials (RCTs) were conducted to examine the impact of a brief, audio-recorded, mindfulness intervention on patients' pain in the clinic waiting room. Method: Study 1 examined an 8-min mindfulness recording delivered before a provider visit; Study 2 examined a 5-min mindfulness recording after a provider visit; and Study 3 examined a 4-min mindfulness recording before a provider visit. Time- and attention-matched control conditions were used in each study. Studies 1 and 2 were conducted in an academic cancer hospital. Study 3 was conducted at a walk-in orthopedic clinic. Pain intensity was measured in each of the three studies. Anxiety and depression symptoms were measured in Studies 2 and 3. Pain unpleasantness was measured in Study 3. Results: A brief (i.e., 4- to 8-min), audio-recorded mindfulness intervention decreased patients' pain intensity in the clinic waiting room, whether delivered before (Study 1 Cohen's d=1.01, Study 3 Cohen's d=0.39) or after (Study 2 Cohen's d=0.89) a provider visit. Mindfulness had a significant effect on anxiety symptoms in both studies in which it was measured. No effect on depression symptoms was observed. Conclusions: Results from these three pilot RCTs indicate brief, audio-recorded, mindfulness interventions may be capable of quickly decreasing clinical symptoms. As such, embedding brief, audio-recorded, mindfulness interventions in clinic waiting rooms may have the potential to improve patient outcomes. The continued investigation of this intervention approach is needed. Clinical Trial Registrations: NCT04477278 and NCT06099964.

Premastectomy Radiotherapy and Immediate Breast Reconstruction: A Randomized Clinical Trial.

Importance: Premastectomy radiotherapy (PreMRT) is a new treatment sequence to avoid the adverse effects of radiotherapy on the final breast reconstruction while achieving the benefits of immediate breast reconstruction (IMBR). Objective: To evaluate outcomes among patients who received PreMRT and regional nodal irradiation (RNI) followed by mastectomy and IMBR. Design, Setting, and Participants: This was a phase 2 single-center randomized clinical trial conducted between August 3, 2018, and August 2, 2022, evaluating the feasibility and safety of PreMRT and RNI (including internal mammary lymph nodes). Patients with cT0-T3, N0-N3b breast cancer and a recommendation for radiotherapy were eligible. Intervention: This trial evaluated outcomes after PreMRT followed by mastectomy and IMBR. Patients were randomized to receive either hypofractionated (40.05 Gy/15 fractions) or conventionally fractionated (50 Gy/25 fractions) RNI. Main Outcome and Measures: The primary outcome was reconstructive failure, defined as complete autologous flap loss. Demographic, treatment, and outcomes data were collected, and associations between multiple variables and outcomes were evaluated. Analysis was performed on an intent-to-treat basis. Results: Fifty patients were enrolled. Among 49 evaluable patients, the median age was 48 years (range, 31-72 years), and 46 patients (94%) received neoadjuvant systemic therapy. Twenty-five patients received 50 Gy in 25 fractions to the breast and 45 Gy in 25 fractions to regional nodes, and 24 patients received 40.05 Gy in 15 fractions to the breast and 37.5 Gy in 15 fractions to regional nodes, including internal mammary lymph nodes. Forty-eight patients underwent mastectomy with IMBR, at a median of 23 days (IQR, 20-28.5 days) after radiotherapy. Forty-one patients had microvascular autologous flap reconstruction, 5 underwent latissimus dorsi pedicled flap reconstruction, and 2 had tissue expander placement. There were no complete autologous flap losses, and 1 patient underwent tissue expander explantation. Eight of 48 patients (17%) had mastectomy skin flap necrosis of the treated breast, of whom 1 underwent reoperation. During follow-up (median, 29.7 months [range, 10.1-65.2 months]), there were no locoregional recurrences or distant metastasis. Conclusions and Relevance: This randomized clinical trial found PreMRT and RNI followed by mastectomy and microvascular autologous flap IMBR to be feasible and safe. Based on these results, a larger randomized clinical trial of hypofractionated vs conventionally fractionated PreMRT has been started (NCT05774678). Trial Registration: ClinicalTrials.gov Identifier: NCT02912312.

Peripheral Blood Mononuclear Cell Gene Expression Associated with Pulmonary Microvascular Perfusion: The Multi-Ethnic Study of Atherosclerosis Chronic Obstructive Pulmonary Disease.

Rationale: Chronic obstructive pulmonary disease (COPD) and emphysema are associated with endothelial damage and altered pulmonary microvascular perfusion. The molecular mechanisms underlying these changes are poorly understood in patients, in part because of the inaccessibility of the pulmonary vasculature. Peripheral blood mononuclear cells (PBMCs) interact with the pulmonary endothelium. Objectives: To test the association between gene expression in PBMCs and pulmonary microvascular perfusion in COPD. Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study recruited two independent samples of COPD cases and controls with ⩾10 pack-years of smoking history. In both samples, pulmonary microvascular blood flow, pulmonary microvascular blood volume, and mean transit time were assessed on contrast-enhanced magnetic resonance imaging, and PBMC gene expression was assessed by microarray. Additional replication was performed in a third sample with pulmonary microvascular blood volume measures on contrast-enhanced dual-energy computed tomography. Differential expression analyses were adjusted for age, gender, race/ethnicity, educational attainment, height, weight, smoking status, and pack-years of smoking. Results: The 79 participants in the discovery sample had a mean age of 69 ± 6 years, 44% were female, 25% were non-White, 34% were current smokers, and 66% had COPD. There were large PBMC gene expression signatures associated with pulmonary microvascular perfusion traits, with several replicated in the replication sets with magnetic resonance imaging (n = 47) or dual-energy contrast-enhanced computed tomography (n = 157) measures. Many of the identified genes are involved in inflammatory processes, including nuclear factor-κB and chemokine signaling pathways. Conclusions: PBMC gene expression in nuclear factor-κB, inflammatory, and chemokine signaling pathways was associated with pulmonary microvascular perfusion in COPD, potentially offering new targetable candidates for novel therapies.

Where are the inequalities in colorectal cancer care in a country with universal healthcare? A systematic review and narrative synthesis.

OBJECTIVE: Patients diagnosed with colorectal cancer living in more deprived areas experience worse survival than those in more affluent areas. Those living in more deprived areas face barriers to accessing timely, quality healthcare. These barriers may contribute to socioeconomic inequalities in survival. We evaluated the literature for any association between socioeconomic group, hospital delay and treatments received among patients with colorectal cancer in the UK, a country with universal healthcare. DESIGN: MEDLINE, EMBASE, CINAHL, CENTRAL, SCIE, AMED and PsycINFO were searched from inception to January 2023. Grey literature, including HMIC, BASE and Google Advanced Search, and forward and backward citation searches were conducted. Two reviewers independently reviewed titles, abstracts and full-text articles. Observational UK-based studies were included if they reported socioeconomic measures and an association with either hospital delay or treatments received. The QUIPS tool assessed bias risk, and a narrative synthesis was conducted. The review is reported to Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020. RESULTS: 41 of the 7209 identified references were included. 12 studies evaluated 7 different hospital intervals. There was a significant association between area-level deprivation and a longer time from first presentation in primary care to diagnosis. 32 studies evaluated treatments received. There were socioeconomic inequalities in surgery and chemotherapy but not radiotherapy. CONCLUSION: Patients with colorectal cancer face inequalities across the cancer care continuum. Further research is needed to understand why and what evidence-based actions can reduce these inequalities in treatment. Qualitative research of patients and clinicians conducted across various settings would provide a rich understanding of the complex factors that drive these inequalities. Further research should also consider using a causal approach to future studies to considerably strengthen the interpretation. Clinicians can try and mitigate some potential causes of colorectal cancer inequalities, including signposting to financial advice and patient transport schemes. PROSPERO REGISTRATION NUMBER: CRD42022347652.

Mucus plugs in the airways of asthmatic subjects and smoking status.

BACKGROUND: Mucus plugs have been described in the airways of asthmatic subjects, particularly those with associated with type 2 inflammation and sputum eosinophilia. In the current study we addressed the question of whether smoking, neutrophilic inflammation and airway dimensions affected the prevalence of mucus plugs. METHODS: In a cohort of moderate to severe asthmatics (n = 50), including a group of ex-smokers and current smokers, the prevalence of mucus plugs was quantified using a semi-quantitative score based on thoracic computerized tomography. The relationships between mucus score, sputum inflammatory profile and airway architecture were tested according to patient's smoking status. RESULTS: Among the asthmatics (37% former or active smokers), 74% had at least one mucus plug. The median score was 3 and was unrelated to smoking status. A significant but weak correlation was found between mucus score, FEV1 and FEV1/FVC. Mucus score was significantly correlated with sputum eosinophils. Among former and active smokers, mucus score was correlated with sputum neutrophils. Mucus score was positively associated with FeNO in non-smoking subjects. The lumen dimensions of the main and lobar bronchi were significantly inversely correlated with mucus score. CONCLUSION: Airway mucus plugs could define an asthma phenotype with altered airway architecture and can occur in asthmatic subjects with either neutrophilic or eosinophilic sputum according to their smoking status.

Benefits of Implementing Reflex Genomic Analysis for Nonsmall Cell Lung Cancer.

BACKGROUND: Molecular biomarker analysis is standard of care in advanced nonsmall cell lung cancer (NSCLC). Pathologist-driven reflex testing protocols are one approach to initiating this analysis. Two years after insourcing genomic analysis at our institution, a reflex testing protocol for advanced NSCLC was initiated. METHODS: A retrospective review of the records of 578 NSCLC biopsies was performed to assess the impact of 3 genomic testing workflows (send-out, in-house clinician-ordered, and in-house reflex) on time to initiation of molecular testing [initiation time (IT)], reporting time (RT), proportion of test failures, and test ordering practices. The proportion of test failures by test methodology was also assessed. RESULTS: IT was lowest for reflex protocol orders (mean weekdays: 30.0 send-out, 27.4 in-house clinician-ordered, 0.95 reflex). Test failure was highest for send-out testing (31.7% vs. 10% each for in-house clinician-ordered and reflex). RT remained consistent across the 3 workflows (mean weekdays: 11.1 send-out, 11.9 in-house clinician-ordered, and 11.4 reflex). Guideline-congruent molecular testing increased upon insourcing genomic analysis and again upon implementing reflex testing with a reduction in nonbiomarker informed care (58.8% send-out, 19.5% in-house clinician-ordered, 11.5% reflex). CONCLUSIONS: Implementation of reflex in-house genomic analysis for advanced NSCLC ensured consistency in RT and significantly decreased IT and proportion of test failures. Insourcing genomic analysis and thoughtful care pathway design improve equitable access to molecular biomarker analysis and mitigate nonbiomarker informed cancer care in NSCLC.

Tape-Reinforced Graft Suturing and Retensioning of Adjustable-Loop Cortical Buttons Improve Quadriceps Tendon Autograft Biomechanics in Anterior Cruciate Ligament Reconstruction: A Cadaveric Study.

PURPOSE: To investigate the biomechanical effects of tape-reinforced graft suturing and graft retensioning for all-soft tissue quadriceps tendon (ASTQT) anterior cruciate ligament reconstruction (ACLR) in a full-construct human cadaveric model. METHODS: Harvested cadaveric ASTQT grafts were assigned to either (1) double-suspensory adjustable-loop cortical button device (ALD) fixation in which both graft ends were fixed with a suspensory fixation device with (n = 5) or without (n = 5) tape-reinforced suturing or (2) single-suspensory distal tendon fixation in which only the patellar end was fixed with an ALD (n = 5) or fixed-loop cortical button device (FLD) (n = 5). All specimens were prepared using a No. 2 whipstitch technique, and tape-reinforced specimens had an integrated braided tape implant. Graft preparation time was recorded for double-suspensory constructs. Samples were tested on an electromechanical testing machine using a previously published protocol simulating rehabilitative kinematics and loading. RESULTS: Tape-reinforced graft suturing resulted in greater graft load retention after cycling (11.9% difference, P = .021), less total elongation (mean [95% confidence interval (CI)], 5.57 mm [3.50-7.65 mm] vs 32.14 mm [25.38-38.90 mm]; P < .001), greater ultimate failure stiffness (mean [95% CI], 171.9 N/mm [158.8-185.0 N/mm] vs 119.4 N/mm [108.7-130.0 N/mm]; P < .001), and less graft preparation time (36.4% difference, P < .001) when compared with unreinforced specimens. Retensioned ALD constructs had less cyclic elongation compared with FLD constructs (mean total elongation [95% CI], 7.04 mm [5.47-8.61 mm] vs 12.96 mm [8.67-17.26 mm]; P = .004). CONCLUSIONS: Tape-reinforced graft suturing improves time-zero ASTQT ACLR construct biomechanics in a cadaveric model with 83% less total elongation, 44% greater stiffness, and reduced preparation time compared with a whipstitched graft without tape reinforcement. ALD fixation improves construct mechanics when compared with FLD fixation as evidenced by 46% less total elongation. CLINICAL RELEVANCE: Tape-reinforced implants and graft retensioning using ALDs improve time-zero ACLR graft construct biomechanics in a time-zero biomechanical model. Clinical studies will be necessary to determine whether these implants improve clinical outcomes including knee laxity and the incidence of graft rupture.

Racial and Ethnic Differences in Long-Term Adverse Radiation Therapy Effects Among Breast Cancer Survivors.

PURPOSE: Breast and skin changes are underrecognized side effects of radiation therapy for breast cancer, which may have long-term implications for quality of life (QOL). Racial and ethnic disparities in breast cancer outcomes, including long-term QOL differences after breast radiation therapy, are poorly understood. METHODS AND MATERIALS: We conducted a cross-sectional survey study of patients from the Texas Cancer Registry who received diagnoses of stage 0-II breast cancer from 2009 to 2014 and treated with lumpectomy and radiation therapy; 2770 patients were sampled and 631 responded (23%). The BREAST-Q Adverse Effects of Radiation overall score and subindices measured the effect of radiation therapy on breast tissue. Multivariable logistic regression evaluated associations of demographic and treatment characteristics with outcomes. RESULTS: The median age was 57 years (IQR, 48-65), median time from diagnosis to survey response 9 years (IQR, 7-10), and the cohort included 62 Asian American or Pacific Islander (9.8%), 11 American Indian or Alaskan Native (AIAN) (1.7%), 161 Black (25.5%), 144 Hispanic (22.8%), and 253 White (40.1%) patients. Mean BREAST-Q Adverse Effects of Radiation score was worse for AIAN patients (-22.2; 95% CI, -39.9 to -4.6; P = .01), Black patients (-10.8; 95% CI, -16.1 to -5.5; P < .001), and Hispanic patients (-7.8; 95% CI, -13.0 to -2.5; P = .004) compared with White patients, age <50 compared with ≥65 (effect size -8.6; 95% CI, -14.0 to -3.2; P = .002), less than a college education (-5.8; 95% CI, -10.0 to -1.6; P = .01), bra cup size of D/E versus A/B (-5.3; 95% CI, -9.9 to -0.65; P = .03), and current smokers (-11.3; 95% CI, -18.3 to -4.2; P = .002). AIAN, Black, and Hispanic patients reported worse changes in skin pigmentation, telangiectasias, dryness, soreness, and/or irritation compared with White patients. CONCLUSIONS: AIAN, Black, and Hispanic patients reported substantially worse long-term breast and skin QOL outcomes after radiation therapy. Additional work is needed to understand these differences and how to alleviate them.

Patient Interest in Exploring Nonsurgical Treatment Approaches for Early-Stage Breast Cancer: A Qualitative Study.

PURPOSE: Advances in radiation therapy have enabled the ability to deliver ablative treatments, but there has been limited application of these treatments to early-stage breast cancers with a goal of omitting surgery. The purpose of this study was to explore patient interest in pursuing nonsurgical treatment approaches for their early-stage breast cancer. METHODS AND MATERIALS: We conducted a qualitative study involving interviews with 21 patients with early-stage breast cancer who were eligible for participation in a phase 2 clinical trial offering omission of definitive surgery. Interviews were transcribed and an inductive, thematic analysis was performed by 3 independent reviewers to generate themes and subthemes. RESULTS: Data analysis revealed the following factors that affected patient willingness and desire to explore nonsurgical treatment options: (1) perceptions and feelings about their cancer; (2) current quality of life and the level of support available in their daily life; (3) external conversations focusing on family members' and friends' experiences with cancer and/or cancer treatments; (4) personal health care experiences, including their current breast cancer diagnosis; (5) perceptions and feelings about their physicians; (6) conversations with their physicians about their treatment options; and (7) self-identified desire to direct care decisions. Specifically, patients verbalized fearing surgery and surgical recovery; wanting to preserve their breast(s); the prior negative surgical experiences of friends, family, and themselves; a desire to receive treatment per the latest research; wanting to match the level of treatment with the severity of their cancer; and other comorbidities as reasons for wanting to explore omitting surgery. CONCLUSIONS: Our findings demonstrate an unmet need directed by patient interest to explore nonsurgical options for early-stage, biologically favorable breast cancer. These results may shape conversations around shared decision-making and clinical trial design, and result in more personalized treatment options for women with early-stage breast cancer.

Where are the inequalities in ovarian cancer care in a country with universal healthcare? A systematic review and narrative synthesis.

INTRODUCTION: Patients diagnosed with ovarian cancer from more deprived areas may face barriers to accessing timely, quality healthcare. We evaluated the literature for any association between socioeconomic group, treatments received and hospital delay among patients diagnosed with ovarian cancer in the United Kingdom, a country with universal healthcare. METHODS: We searched MEDLINE, EMBASE, CINAHL, CENTRAL, SCIE, AMED, PsycINFO and HMIC from inception to January 2023. Forward and backward citation searches were conducted. Two reviewers independently reviewed titles, abstracts, and full-text articles. UK-based studies were included if they reported socioeconomic measures and an association with either treatments received or hospital delay. The inclusion of studies from one country ensured greater comparability. Risk of bias was assessed using the QUIPS tool, and a narrative synthesis was conducted. The review is reported to PRISMA 2020 and registered with PROSPERO [CRD42022332071]. RESULTS: Out of 2876 references screened, ten were included. Eight studies evaluated treatments received, and two evaluated hospital delays. We consistently observed socioeconomic inequalities in the likelihood of surgery (range of odds ratios 0.24-0.99) and chemotherapy (range of odds ratios 0.70-0.99) among patients from the most, compared with the least, deprived areas. There were no associations between socioeconomic groups and hospital delay. POLICY SUMMARY: Ovarian cancer treatments differed between socioeconomic groups despite the availability of universal healthcare. Further research is needed to understand why, though suggested reasons include patient choice, health literacy, and financial and employment factors. Qualitative research would provide a rich understanding of the complex factors that drive these inequalities.