The Acceptance and Use of Digital Technologies for Self-Reporting Medication Safety Events After Care Transitions to Home in Patients With Cancer: Survey Study.

BACKGROUND: Actively engaging patients with cancer and their families in monitoring and reporting medication safety events during care transitions is indispensable for achieving optimal patient safety outcomes. However, existing patient self-reporting systems often cannot address patients' various experiences and concerns regarding medication safety over time. In addition, these systems are usually not designed for patients' just-in-time reporting. There is a significant knowledge gap in understanding the nature, scope, and causes of medication safety events after patients' transition back home because of a lack of patient engagement in self-monitoring and reporting of safety events. The challenges for patients with cancer in adopting digital technologies and engaging in self-reporting medication safety events during transitions of care have not been fully understood. OBJECTIVE: We aim to assess oncology patients' perceptions of medication and communication safety during care transitions and their willingness to use digital technologies for self-reporting medication safety events and to identify factors associated with their technology acceptance. METHODS: A cross-sectional survey study was conducted with adult patients with breast, prostate, lung, or colorectal cancer (N=204) who had experienced care transitions from hospitals or clinics to home in the past 1 year. Surveys were conducted via phone, the internet, or email between December 2021 and August 2022. Participants' perceptions of medication and communication safety and perceived usefulness, ease of use, attitude toward use, and intention to use a technology system to report their medication safety events from home were assessed as outcomes. Potential personal, clinical, and psychosocial factors were analyzed for their associations with participants' technology acceptance through bivariate correlation analyses and multiple logistic regressions. RESULTS: Participants reported strong perceptions of medication and communication safety, positively correlated with medication self-management ability and patient activation. Although most participants perceived a medication safety self-reporting system as useful (158/204, 77.5%) and easy to use (157/204, 77%), had a positive attitude toward use (162/204, 79.4%), and were willing to use such a system (129/204, 63.2%), their technology acceptance was associated with their activation levels (odds ratio [OR] 1.83, 95% CI 1.12-2.98), their perceptions of communication safety (OR 1.64, 95% CI 1.08-2.47), and whether they could receive feedback after self-reporting (OR 3.27, 95% CI 1.37-7.78). CONCLUSIONS: In general, oncology patients were willing to use digital technologies to report their medication events after care transitions back home because of their high concerns regarding medication safety. As informed and activated patients are more likely to have the knowledge and capability to initiate and engage in self-reporting, developing a patient-centered reporting system to empower patients and their families and facilitate safety health communications will help oncology patients in addressing their medication safety concerns, meeting their care needs, and holding promise to improve the quality of cancer care.

ctDNA transiting into urine is ultrashort and facilitates noninvasive liquid biopsy of HPV+ oropharyngeal cancer.

BACKGROUNDTransrenal cell-free tumor DNA (TR-ctDNA), which transits from the bloodstream into urine, has the potential to enable noninvasive cancer detection for a wide variety of nonurologic cancer types.MethodsUsing whole-genome sequencing, we discovered that urine TR-ctDNA fragments across multiple cancer types are predominantly ultrashort (<50 bp) and, therefore, likely to be missed by conventional ctDNA assays. We developed an ultrashort droplet digital PCR assay to detect TR-ctDNA originating from HPV-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC) and confirmed that assaying ultrashort DNA is critical for sensitive cancer detection from urine samples.ResultsTR-ctDNA was concordant with plasma ctDNA for cancer detection in patients with HPV+ OPSCC. As proof of concept for using urine TR-ctDNA for posttreatment surveillance, in a small longitudinal case series, TR-ctDNA showed promise for noninvasive detection of recurrence of HPV+ OPSCC.ConclusionOur data indicate that focusing on ultrashort fragments of TR-ctDNA will be important for realizing the full potential of urine-based cancer diagnostics. This has implications for urine-based detection of a wide variety of cancer types and for facilitating access to care through at-home specimen collections.FundingNIH grants R33 CA229023, R21 CA225493; NIH/National Cancer Institute grants U01 CA183848, R01 CA184153, and P30CA046592; American Cancer Society RSG-18-062-01-TBG; American Cancer Society Mission Boost grant MBGI-22-056-01-MBG; and the A. Alfred Taubman Medical Research Institute.

Sotorasib with panitumumab in chemotherapy-refractory KRASG12C-mutated colorectal cancer: a phase 1b trial.

The current third-line (and beyond) treatment options for RAS-mutant metastatic colorectal cancer have yielded limited efficacy. At the time of study start, the combination of sotorasib, a KRAS (Kirsten rat sarcoma viral oncogene homolog)-G12C inhibitor, and panitumumab, an epidermal growth factor receptor (EGFR) inhibitor, was hypothesized to overcome treatment-induced resistance. This phase 1b substudy of the CodeBreaK 101 master protocol evaluated sotorasib plus panitumumab in patients with chemotherapy-refractory KRASG12C-mutated metastatic colorectal cancer. Here, we report the results in a dose-exploration cohort and a dose-expansion cohort. Patients received sotorasib (960 mg, once daily) plus panitumumab (6 mg kg-1, once every 2 weeks). The primary endpoints were safety and tolerability. Secondary endpoints included efficacy and pharmacokinetics. Exploratory biomarkers at baseline were assessed. Forty-eight patients (dose-exploration cohort, n = 8; dose-expansion cohort, n = 40) were treated. Treatment-related adverse events of any grade and grade ≥3 occurred in 45 (94%) and 13 (27%) patients, respectively. In the dose-expansion cohort, the confirmed objective response rate was 30.0% (95% confidence interval (CI) 16.6%, 46.5%). Median progression-free survival was 5.7 months (95% CI 4.2, 7.7 months). Median overall survival was 15.2 months (95% CI 12.5 months, not estimable). Prevalent genomic coalterations included APC (84%), TP53 (74%), SMAD4 (33%), PIK3CA (28%) and EGFR (26%). Sotorasib-panitumumab demonstrated acceptable safety with promising efficacy in chemotherapy-refractory KRASG12C-mutated metastatic colorectal cancer. ClinicalTrials.gov identifier: NCT04185883 .

Long-Term Results of Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy: The Randomized Phase II OPRA Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.To assess long-term risk of local tumor regrowth, we report updated organ preservation rate and oncologic outcomes of the OPRA trial (ClinicalTrials.gov identifier: NCT02008656). Patients with stage II/III rectal cancer were randomly assigned to receive induction chemotherapy followed by chemoradiation (INCT-CRT) or chemoradiation followed by consolidation chemotherapy (CRT-CNCT). Patients who achieved a complete or near-complete response after finishing treatment were offered watch-and-wait (WW). Total mesorectal excision (TME) was recommended for those who achieved an incomplete response. The primary end point was disease-free survival (DFS). The secondary end point was TME-free survival. In total, 324 patients were randomly assigned (INCT-CRT, n = 158; CRT-CNCT, n = 166). Median follow-up was 5.1 years. The 5-year DFS rates were 71% (95% CI, 64 to 79) and 69% (95% CI, 62 to 77) for INCT-CRT and CRT-CNCT, respectively (P = .68). TME-free survival was 39% (95% CI, 32 to 48) in the INCT-CRT group and 54% (95% CI, 46 to 62) in the CRT-CNCT group (P = .012). Of 81 patients with regrowth, 94% occurred within 2 years and 99% occurred within 3 years. DFS was similar for patients who underwent TME after restaging (64% [95% CI, 53 to 78]) and patients in WW who underwent TME after regrowth (64% [95% CI, 53 to 78]; P = .94). Updated analysis continues to show long-term organ preservation in half of the patients with rectal cancer treated with total neoadjuvant therapy. In patients who enter WW, most cases of tumor regrowth occur in the first 2 years.

Cobimetinib Plus Vemurafenib in Patients With Solid Tumors With BRAF Mutations: Results From the Targeted Agent and Profiling Utilization Registry Study.

PURPOSE: The Targeted Agent and Profiling Utilization Registry Study is a phase II basket study evaluating antitumor activity of commercially available targeted agents in patients with advanced cancers with genomic alterations known to be drug targets. The results in a cohort of patients with solid tumors with BRAF mutations treated with cobimetinib plus vemurafenib are reported. METHODS: Eligible patients had measurable disease (RECIST v.1.1), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as complete response (CR) or partial response (PR) or stable disease of at least 16-weeks duration (SD16+). Low-accruing histology-specific cohorts with BRAF mutations treated with cobimetinib plus vemurafenib were collapsed into a single histology-pooled cohort for this analysis. The results were evaluated on the basis of a one-sided exact binomial test with a null DC rate of 15% versus 35% (power, .82; α, .10). The secondary end points were objective response (OR), progression-free survival, overall survival, duration of response, duration of stable disease, and safety. RESULTS: Thirty-one patients with solid tumors with BRAF mutations were enrolled. Twenty-eight patients were evaluable for efficacy. Patients had tumors with BRAF V600E (n = 26), K601E (n = 2), or other (n = 3) mutations. Two patients with CR (breast and ovarian cancers; V600E), 14 with PR (13 V600E, one N581I), and three with SD16+ (two V600E, one T599_V600insT) were observed with a DC rate of 68% (P < .0001; one-sided 90% CI, 54 to 100) and an OR rate of 57% (95% CI, 37 to 76). Nineteen patients experienced ≥one drug-related grade 3-5 adverse event or serious adverse event including one death attributed to treatment-related kidney injury. CONCLUSION: Cobimetinib plus vemurafenib showed antitumor activity in patients with advanced solid tumors with BRAF V600E mutations; additional study is warranted to confirm the antitumor activity in tumors with non-V600E BRAF mutations.

Diacutaneous Fibrolysis: An Update on Research into Musculoskeletal and Neural Clinical Entities.

Diacutaneous Fibrolysis (DF) is an instrumentally assisted manual therapy technique defined as "a specific instrumental intervention for normalizing the musculoskeletal system function after a precise diagnosis and preserving the skin's integrity". The aim of this technique is soft tissue mobilization with the assistance of specially designed, hook-shaped steel instruments in different musculoskeletal structures, such as the myofascia, aponeurosis, tendons, ligaments and scar tissues. Due to discrepant results between previous reviews and the quite abundant new evidence provided by recently published randomized clinical trials, we propound this narrative review to provide an update on the scientific evidence related to the fundamentals and clinical efficacy of DF. Current evidence primarily supports the mechanical effect of DF on connective soft tissues. Diminished deep tendon reflex and rigidity have been registered after the implementation of DF in healthy subjects. Though there is still much to uncover, scientific evidence supports the use of the technique for the clinical treatment of subacromial impingement syndrome, chronic lateral epicondylalgia, chronic patellofemoral pain syndrome, mild to moderate carpal tunnel syndrome, hamstring shortening, temporomandibular disorders, tension-type headache and chronic low back pain. Additional data are essential for better recommendations in the clinical practice of DF.

Successful Treatment of Recurrent Colonic Adenocarcinoma with Metastatic Tumor Thrombus in the Superior Mesenteric Vein with Surgical Excision and Venous Reconstruction.

BACKGROUND Patients cured of Hodgkin lymphoma (HL) are at increased risk of second malignancies, such as lung, breast, and colon cancer. Isolated metastasis of these malignancies to the vasculature is rare. We present a unique case of a patient cured of HL who developed colon cancer and later presented with an isolated metastases of colon cancer to the superior mesenteric vein. The patient is now in complete remission 5 years after surgical excision of the superior mesenteric vein metastases followed by chemotherapy. CASE REPORT A 56-year-old woman presented with a past medical history notable for stage III HL diagnosed at age 13 years that was treated by splenectomy, chemotherapy, and mantle with inverted Y radiation. She underwent a right nephrectomy at age 51 years for renal cell carcinoma. At age 56, an 8-cm mass in the transverse colon was found during surveillance imaging. She underwent right hemicolectomy for pathological stage IIA (T3N0M0) adenocarcinoma. A liver adenoma was identified a year later. Two years after hemicolectomy, an abdominal recurrence was identified, and she underwent a resection of a superior mesenteric vein mass with porto-mesenteric reconstruction. Pathology revealed metastatic colonic adenocarcinoma, 1 of 7 lymph nodes positive for cancer, and clear margins. She received 6 months of fluorouracil chemotherapy and remained free of recurrences for 5 years. CONCLUSIONS Isolated vascular recurrences of colon cancer can be cured with resection and systemic chemotherapy. Diagnosis and treatment of venous recurrences remains challenging owing to the lack or percutaneous access for biopsy and the difficulty of venous reconstruction.

Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): an international, multicentre, randomised, double-blind, phase 3 study.

BACKGROUND: There is a paucity of effective systemic therapy options for patients with advanced, chemotherapy-refractory colorectal cancer. We aimed to evaluate the efficacy and safety of fruquintinib, a highly selective and potent oral inhibitor of vascular endothelial growth factor receptors (VEGFRs) 1, 2, and 3, in patients with heavily pretreated metastatic colorectal cancer. METHODS: We conducted an international, randomised, double-blind, placebo-controlled, phase 3 study (FRESCO-2) at 124 hospitals and cancer centres across 14 countries. We included patients aged 18 years or older (≥20 years in Japan) with histologically or cytologically documented metastatic colorectal adenocarcinoma who had received all current standard approved cytotoxic and targeted therapies and progressed on or were intolerant to trifluridine-tipiracil or regorafenib, or both. Eligible patients were randomly assigned (2:1) to receive fruquintinib (5 mg capsule) or matched placebo orally once daily on days 1-21 in 28-day cycles, plus best supportive care. Stratification factors were previous trifluridine-tipiracil or regorafenib, or both, RAS mutation status, and duration of metastatic disease. Patients, investigators, study site personnel, and sponsors, except for selected sponsor pharmacovigilance personnel, were masked to study group assignments. The primary endpoint was overall survival, defined as the time from randomisation to death from any cause. A non-binding futility analysis was done when approximately one-third of the expected overall survival events had occurred. Final analysis occurred after 480 overall survival events. This study is registered with ClinicalTrials.gov, NCT04322539, and EudraCT, 2020-000158-88, and is ongoing but not recruiting. FINDINGS: Between Aug 12, 2020, and Dec 2, 2021, 934 patients were assessed for eligibility and 691 were enrolled and randomly assigned to receive fruquintinib (n=461) or placebo (n=230). Patients had received a median of 4 lines (IQR 3-6) of previous systemic therapy for metastatic disease, and 502 (73%) of 691 patients had received more than 3 lines. Median overall survival was 7·4 months (95% CI 6·7-8·2) in the fruquintinib group versus 4·8 months (4·0-5·8) in the placebo group (hazard ratio 0·66, 95% CI 0·55-0·80; p<0·0001). Grade 3 or worse adverse events occurred in 286 (63%) of 456 patients who received fruquintinib and 116 (50%) of 230 who received placebo; the most common grade 3 or worse adverse events in the fruquintinib group included hypertension (n=62 [14%]), asthenia (n=35 [8%]), and hand-foot syndrome (n=29 [6%]). There was one treatment-related death in each group (intestinal perforation in the fruquintinib group and cardiac arrest in the placebo group). INTERPRETATION: Fruquintinib treatment resulted in a significant and clinically meaningful benefit in overall survival compared with placebo in patients with refractory metastatic colorectal cancer. These data support the use of fruquintinib as a global treatment option for patients with refractory metastatic colorectal cancer. Ongoing analysis of the quality of life data will further establish the clinical benefit of fruquintinib in this patient population. FUNDING: HUTCHMED.

Association between age, sex and cervical and upper cervical rotation tests. Descriptive and correlational study in healthy volunteers.

Background: Active cervical spine rotation (ACROM Rot) shows cervical rotation and flexion rotation test (FRT); side-bending rotation test (SBRT) and upper cervical axial rotation test (C0-C2ART) are described to measure upper cervical rotation. The objectives of this study are (1) to describe the normal range of motion (ROM) of ACROM Rot, and the ROM in FRT, SBRT and C0-C2ART tests; (2) to explore the correlation among the four tests and (3) to investigate the influence of age and sex in their ROM. Methods: A cross-sectional study was carried out with healthy volunteers from 18 to 75 years of age. Tests were measured using a CROM device and a bubble inclinometer. Descriptive analysis was performed to establish normative data for the ROM tests. Correlation analysis was conducted to understand the relation between upper and global cervical rotation ROM and among the three upper cervical rotation tests. Linear regression models were developed to understand the influence of age and sex in the ROM of all tests. Results: Normative values were obtained from 122 healthy volunteers (50% male), by sex and age strata. The degree of correlation ranged between 0.582 (p < 0.01) for FRT and ACROM Rot left and 0.217 (p < 0.05) for SBRT and C0-C2ART left. Linear regression models showed the influence of sex for ACROM Rot right (men -4.64° less than women), SBRT (men -4.1° less than women) left and C0-C2ART right and left (men -2.24° and -1.78° less than women). The age influenced rotation ROM with a decrease for every 10 years of -2.11° and -1.96° for ACROM Rot right and left, of -1.72° and -1.26° for FRT right and left and -0.58° and -0.41° for C0-C2ART right and left in the linear regression models. No association was found between age and SBRT (p = 0.63 for right SBRT and p = 0.49 for left SBRT). Conclusion: Weak-to-moderate correlation was found between the upper cervical spine rotation tests and with the ACROM. Women had a larger ROM in ACROM Rot right, SBRT left and C0-C2ART. Decreases in ROM related with age were observed for ACROM Rot, FRT and C0-C2ART but not for SBRT.

Confirmatory DPYD Testing in Patients Receiving Fluoropyrimidines Who are Suspected DPYD Variant Carriers Based on a Genetic Data Repository.

Using pharmacogenetics (PGx) to inform clinical decision making can benefit patients but clinical use of PGx testing has been limited. Existing genetics data obtained in the course of research could be used to identify patients who are suspected, but have not yet been confirmed, to carry clinically actionable genotypes, in whom confirmatory genetic testing could be conducted for highly efficient PGx implementation. Herein, we demonstrate that it is regulatorily and technically feasible to implement PGx by identifying suspected carriers of actionable genotypes within an institutional genetics data repository and conduct confirmatory PGx testing immediately prior to that patient receiving the PGx-relevant drug, using a case study of DPYD testing prior to fluoropyrimidine chemotherapy. In 2 years since launching this program, ~ 3,000 suspected DPYD carriers have been passively monitored and one confirmed DPYD carrier was prevented from receiving unacceptably toxic fluoropyrimidine treatment, for minimal cost and effort. Now that we have demonstrated the feasibility of this strategy, we plan to transition to PGx panel testing and expand implementation to other genes and drugs for which the evidence of clinical benefit of PGx-informed treatment is high but PGx testing is not generally conducted. This highly efficient implementation process will maximize the clinical benefits of testing and could be explored at other institutions that have research-only genetic data repositories to expand the number of patients who benefit from PGx-informed treatment while we continue to work toward wide-scale adoption of PGx testing and implementation.

Effects of occipital-atlas stabilization on the upper cervical spine rotation combinations: an in vitro study.

The purpose of this study is to compare axial rotation range of motion for the upper cervical spine during three movements: axial rotation, rotation + flexion + ipsilateral lateral bending and rotation + extension + contralateral lateral bending before and after occiput-atlas (C0-C1) stabilization. Ten cryopreserved C0-C2 specimens (mean age 74 years, range 63-85 years) were manually mobilized in 1. axial rotation, 2. rotation + flexion + ipsilateral lateral bending and 3. rotation + extension + contralateral lateral bending without and with a screw stabilization of C0-C1. Upper cervical range of motion and the force used to generate the motion were measured using an optical motion system and a load cell respectively. The range of motion (ROM) without C0-C1 stabilization was 9.8° ± 3.9° in right rotation + flexion + ipsilateral lateral bending and 15.5° ± 5.9° in left rotation + flexion + ipsilateral lateral bending. With stabilization, the ROM was 6.7° ± 4.3° and 13.6° ± 5.3°, respectively. The ROM without C0-C1 stabilization was 35.1° ± 6.0° in right rotation + extension + contralateral lateral bending and 29.0° ± 6.5° in left rotation + extension + contralateral lateral bending. With stabilization, the ROM was 25.7° ± 6.4° (p = 0.007) and 25.3° ± 7.1°, respectively. Neither rotation + flexion + ipsilateral lateral bending (left or right) or left rotation + extension + contralateral lateral bending reached statistical significance. ROM without C0-C1 stabilization was 33.9° ± 6.7° in right rotation and 28.0° ± 6.9° in left rotation. With stabilization, the ROM was 28.5° ± 7.0° (p = 0.005) and 23.7° ± 8.5° (p = 0.013) respectively. The stabilization of C0-C1 reduced the upper cervical axial rotation in right rotation + extension + contralateral lateral bending and right and left axial rotations; however, this reduction was not present in left rotation + extension + contralateral lateral bending or both combinations of rotation + flexion + ipsilateral lateral bending.

Association between Age, Sex and Cervical Spine Sagittal Plane Motion: A Descriptive and Correlational Study in Healthy Volunteers.

Active motion examination of patients with cervical spine-related pathologies is necessary to establish baseline function, set physical therapy goals, and choose interventions. This study investigated the sagittal plane active range of motion (ROM) of the global (GCS) and upper cervical spine (UCS) in relation to age and sex in healthy volunteers. One hundred twenty-two volunteers aged 18 to 75 years participated. Volunteers were excluded if they displayed any characteristic that could affect cervical spine ROM. GCS and UCS flexion and extension were each measured three times using a CROM device. Linear regression models (LRMs) were developed to explore the relationships between age and sex and GCS and UCS ROM. The LRM for age showed a decrease in GCS flexion (-2.01°), GCS extension (-3.33°), and UCS extension (-1.87°) for every decade of increasing age. The LRM for sex showed that men displayed less ROM than women in GCS extension (-6.52°) and UCS extension (-2.43°). These results suggest an age-related loss of sagittal plane GCS ROM and UCS extension ROM, and sex-related differences in GCS and UCS extension with women having greater motion than men.

Evaluation of biliary toxicity in patients with hepatic artery infusion pumps.

PURPOSE: Identify risk factors for biliary toxicity in patients with colorectal liver metastases who received floxuridine (FUDR) via a surgically implanted hepatic artery infusion pump (HAIP). Describe the incidence of biliary toxicity and evaluate relevant patterns in the biliary toxicity cohort. METHODS: A single center, retrospective, case-control study included adult colorectal cancer patients with liver metastases who received at least one cycle of FUDR via a surgically implanted HAIP from 1 January 2017, to 1 October 2021. Patients were excluded if they had incomplete records, cholangiocarcinoma diagnosis, or received concurrent mitomycin and FUDR. Biliary toxicity criteria derived from existing HAIP literature were utilized to determine whether patients experienced biliary toxicity. Multiple variables were compared by univariate statistical analysis between the biliary toxicity and non-biliary toxicity cohorts to identify potential risk factors for development of FUDR-induced biliary toxicity. RESULTS: Out of 50 patients who had a HAIP implanted, 39 met the inclusion criteria. Five of the 39 patients (12.7%) included in the analysis met the pre-specified biliary toxicity criteria. No risk factors for biliary toxicity were identified. All five patients who developed biliary toxicity demonstrated elevations in alkaline phosphatase (ALP) prior to meeting the toxicity criteria. CONCLUSION: Biliary toxicity remains a significant and therapy-limiting consequence of FUDR administration. Rising ALP may be an early indicator of subsequent biliary toxicity. Future studies with more patients may identify risk factors that can facilitate risk mitigation strategies.

Effects of Contralateral Hip Flexion Angle on the Ober Test.

The Ober test is an orthopedic evaluation procedure used to assess for tightness of the tensor fascia latae (TFL) and iliotibial band (ITB). Multiple versions of this test have been described using different degrees of contralateral hip joint flexion to stabilize the pelvis. The aim of this study was to analyze the hip range of motion (ROM) in the frontal plane and perceived tension produced during the Ober test using four different angles of contralateral hip flexion prepositioning. The secondary objective was to analyze the differences in the Ober test with different contralateral hip flexion angles according to limb dominance. This cross-sectional study included healthy individuals aged 18 years or older. The Ober test was performed on the right and left leg of each participant with the contralateral hip joint stabilized at 0° flexion, 45° flexion, 90° flexion, and maximal flexion. Hip range of motion in the frontal plane (abduction or adduction) was measured using a digital inclinometer. Three measurements were performed on each limb for every angle of contralateral prepositioning, using the average of the three measurements for statistical analysis. Participants were asked to report the location of any perceived tension and the intensity of tension using a Numeric Rating Scale during the test. Twenty-eight participants (17 men and 11 women) were examined. Significant differences in the Ober test hip ROM in the frontal plane (p < 0.01) were observed when comparing different angles of contralateral hip flexion prepositioning. Significant differences between tests were also present for intensity of perceived tension (p ≤ 0.001), except for the intensity of perceived tension between 0° and 45°. No statistically significant differences were observed related to limb dominance (p > 0.05) or gender (p > 0.05), except for the Ober test at 0° (p < 0.001) which was higher in men (9.61° ± 5.01°) than in women (5.05° ± 2.87°). Greater contralateral hip flexion prepositioning during the Ober test results in decreased hip adduction ROM in the tested limb and greater perceived tension in the region of tensor fascia latae-iliotibial band.

Cobimetinib Plus Vemurafenib in Patients With Colorectal Cancer With BRAF Mutations: Results From the Targeted Agent and Profiling Utilization Registry (TAPUR) Study.

PURPOSE: TAPUR is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. The results of a cohort of patients with colorectal cancer (CRC) with BRAF mutations treated with cobimetinib (C) plus vemurafenib (V) are reported. METHODS: Eligible patients had advanced CRC, no standard treatment options, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, tumors with BRAF V600E/D/K/R mutations, and no MAP2K1/2, MEK1/2, or NRAS mutations. C was taken 60 mg orally once daily for 21 days followed by seven days off, and V was taken 960 mg orally twice daily. Simon's two-stage design was used with a primary study end point of objective response or stable disease of at least 16 weeks duration. Secondary end points were progression-free survival, overall survival, and safety. RESULTS: Thirty patients were enrolled from August 2016 to August 2018; all had CRC with a BRAF V600E mutation except one patient with a BRAF K601E mutation. Three patients were not evaluable for efficacy. Eight patients with partial responses and six patients with stable disease of at least 16 weeks duration were observed for disease control and objective response rates of 52% (95% CI, 35 to 65) and 30% (95% CI, 14 to 50), respectively. The null hypothesis of 15% disease control rate was rejected (P < .0001). Thirteen patients had at least one grade 3 adverse event or serious adverse event at least possibly related to C + V: anemia, decreased lymphocytes, dyspnea, diarrhea, elevated liver enzymes, fatigue, hypercalcemia, hypophosphatemia, rash, photosensitivity, and upper gastrointestinal hemorrhage. CONCLUSION: The combination of C + V has antitumor activity in heavily pretreated patients with CRC with BRAF mutations.

Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy.

PURPOSE: Prospective data on the efficacy of a watch-and-wait strategy to achieve organ preservation in patients with locally advanced rectal cancer treated with total neoadjuvant therapy are limited. METHODS: In this prospective, randomized phase II trial, we assessed the outcomes of 324 patients with stage II or III rectal adenocarcinoma treated with induction chemotherapy followed by chemoradiotherapy (INCT-CRT) or chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT) and either total mesorectal excision (TME) or watch-and-wait on the basis of tumor response. Patients in both groups received 4 months of infusional fluorouracil-leucovorin-oxaliplatin or capecitabine-oxaliplatin and 5,000 to 5,600 cGy of radiation combined with either continuous infusion fluorouracil or capecitabine during radiotherapy. The trial was designed as two stand-alone studies with disease-free survival (DFS) as the primary end point for both groups, with a comparison to a null hypothesis on the basis of historical data. The secondary end point was TME-free survival. RESULTS: Median follow-up was 3 years. Three-year DFS was 76% (95% CI, 69 to 84) for the INCT-CRT group and 76% (95% CI, 69 to 83) for the CRT-CNCT group, in line with the 3-year DFS rate (75%) observed historically. Three-year TME-free survival was 41% (95% CI, 33 to 50) in the INCT-CRT group and 53% (95% CI, 45 to 62) in the CRT-CNCT group. No differences were found between groups in local recurrence-free survival, distant metastasis-free survival, or overall survival. Patients who underwent TME after restaging and patients who underwent TME after regrowth had similar DFS rates. CONCLUSION: Organ preservation is achievable in half of the patients with rectal cancer treated with total neoadjuvant therapy, without an apparent detriment in survival, compared with historical controls treated with chemoradiotherapy, TME, and postoperative chemotherapy.

Quantitating and assessing interoperability between electronic health records.

OBJECTIVES: Electronic health records (EHRs) contain a large quantity of machine-readable data. However, institutions choose different EHR vendors, and the same product may be implemented differently at different sites. Our goal was to quantify the interoperability of real-world EHR implementations with respect to clinically relevant structured data. MATERIALS AND METHODS: We analyzed de-identified and aggregated data from 68 oncology sites that implemented 1 of 5 EHR vendor products. Using 6 medications and 6 laboratory tests for which well-accepted standards exist, we calculated inter- and intra-EHR vendor interoperability scores. RESULTS: The mean intra-EHR vendor interoperability score was 0.68 as compared to a mean of 0.22 for inter-system interoperability, when weighted by number of systems of each type, and 0.57 and 0.20 when not weighting by number of systems of each type. DISCUSSION: In contrast to data elements required for successful billing, clinically relevant data elements are rarely standardized, even though applicable standards exist. We chose a representative sample of laboratory tests and medications for oncology practices, but our set of data elements should be seen as an example, rather than a definitive list. CONCLUSIONS: We defined and demonstrated a quantitative measure of interoperability between site EHR systems and within/between implemented vendor systems. Two sites that share the same vendor are, on average, more interoperable. However, even for implementation of the same EHR product, interoperability is not guaranteed. Our results can inform institutional EHR selection, analysis, and optimization for interoperability.

Efficacy of the Motivational Interviewing-Walk Intervention for Chemotherapy-Induced Peripheral Neuropathy and Quality of Life During Oxaliplatin Treatment: A Pilot Randomized Controlled Trial.

BACKGROUND: Oxaliplatin-induced peripheral neuropathy (OIPN) is prevalent among gastrointestinal cancer survivors and often impairs quality of life (QOL). OBJECTIVE: This pilot randomized controlled trial aimed to explore the effect of an 8-week home-based brisk walking (the "MI-Walk") intervention on (1) OIPN severity and (2) QOL at 8 weeks, compared with physical activity (PA) education alone in oxaliplatin-receiving adults with gastrointestinal cancer. INTERVENTIONS/METHODS: Participants (N = 57) recruited from 5 infusion sites received PA education at their second oxaliplatin visit, followed by phone assessments of adverse events over 8 weeks. Half (n = 29) received additional MI-Walk intervention motivational supports (eg, a Fitbit Charge 2 and motivational enhancement therapy sessions). Self-reported OIPN, QOL, and PA were measured before and after intervention. RESULTS: The intervention compared with the control condition had no effect on sensory OIPN (mean difference [] = -0.01; P > .99), motor OIPN (=2.39; P = .17), and QOL (= -1.43; P > .99). Eight-week sensory (=11.48 ± 0.38) and motor OIPN severities ( = 7.48 ± 0.36) were mild but higher than baseline (P ≤ .01). Self-reported PA level increased over time in both groups (=44.85; P = .01). Averaging ≥225 moderate to vigorous PA minutes per week led to less sensory OIPN, particularly finger/hand tingling (= -26.35; P = .01). CONCLUSIONS: This study failed to detect beneficial effects of the MI-Walk intervention; however, the findings suggest that aerobic walking may blunt but not completely prevent OIPN. Further research is necessary. IMPLICATIONS FOR PRACTICE: Although the effectiveness of brisk walking in reducing OIPN is unclear, this study supports prior evidence that moderate to vigorous PA is beneficial and safe during chemotherapy treatment.

In vitro upper cervical spine kinematics: Rotation with combined movements and its variation after alar ligament transection.

Previous studies indicate that maximum upper cervical axial rotation occurs only through a combination of transverse, frontal, and sagittal plane motions. This study explores the relationship between transection of the alar ligament and combined upper cervical axial rotation movements. Ten cryopreserved upper cervical spines were manually mobilized in bilateral axial rotation and two different motion combinations with simultaneous motion in the three anatomical planes: rotation in extension (extension + axial rotation + contralateral lateral bending) and rotation in flexion (flexion + axial rotation + ipsilateral lateral bending). These three motions were performed before and after right alar ligament transection. The occiput-axis axial rotation was measured using an optical motion capture system while measuring the applied load. With intact alar ligament, the axial rotation in flexion showed the lowest range of motion (right, R: 9.81 ± 3.89°; left, L: 15.54 ± 5.89°). Similar results were found between the other two mobilizations: axial rotation (R: 33.87 ± 6.64°; L: 27.99 ± 6.90°) and rotation in extension (R: 35.15 ± 5.97°; L: 28.96 ± 6.47°). After right alar ligament transection, rotation in flexion (particularly in left rotation) showed the largest increase in motion: rotation in flexion (R: 13.78 ± 9.63°; L: 23.04 ± 5.59°), rotation in extension (R: 36.39 ± 7.10°; L: 31.71 ± 7.67°), and axial rotation (R: 38.50 ± 9.47°; L: 31.59 ± 6.55°). Different combinations of movements should be evaluated when analyzing the maximum axial rotation of the upper cervical spine, as axial rotation alone and rotation in extension showed a larger range of motion than rotation in flexion. After unilateral alar ligament injury, rotation to the non-injured side in flexion demonstrates the most movement increase.

Sotorasib for previously treated colorectal cancers with KRASG12C mutation (CodeBreaK100): a prespecified analysis of a single-arm, phase 2 trial.

BACKGROUND: Sotorasib, a specific, irreversible KRASG12C protein inhibitor, has shown monotherapy clinical activity in KRASG12C-mutated solid tumours, including colorectal cancer, in the CodeBreaK100 phase 1 trial. We aimed to investigate the activity and safety of sotorasib in phase 2 of the trial. METHODS: In this single-arm, phase 2 trial, adult patients with KRASG12C-mutated advanced solid tumours were enrolled, from 59 medical centres in 11 countries, if they were aged 18 years or older, had at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, and had an Eastern Cooperative Oncology Group performance status of 1 or lower. Only data for patients with colorectal cancer, enrolled at 33 medical centres in nine countries, are presented from this basket trial. To be enrolled, the patients had to have progressed after receiving fluoropyrimidine, oxaliplatin, and irinotecan treatment. These patients were administered 960 mg sotorasib orally once per day until disease progression, development of unacceptable side-effects, withdrawal of consent, or death. The primary endpoint was objective response (complete or partial response) as assessed by blinded independent central review. Response was evaluated in patients who received at least one dose of sotorasib and had at least one measurable lesion at baseline; safety was evaluated in patients who received at least one dose of sotorasib. This analysis is a prespecified analysis triggered by the phase 2 colorectal cancer cohort. This study is registered with ClinicalTrials.gov, NCT03600883, and is active but no longer recruiting. FINDINGS: On March 1, 2021, at data cutoff, 62 patients with KRASG12C-mutant colorectal cancer had been enrolled between Aug 14, 2019, and May 21, 2020, and had received at least one dose of sotorasib monotherapy. Objective response was observed in six (9·7%, 95% CI 3·6-19·9) of 62 patients, all with partial response. Treatment-related adverse events at grade 3 occurred in six (10%) patients, the most common of which was diarrhoea (two [3%] of 62 patients), and at grade 4 occurred in one (2%) patient (blood creatine phosphokinase increase); no fatal events were recorded. Serious treatment-related adverse events occurred in two (3%) patients (back pain and acute kidney injury). INTERPRETATION: Although the 9·7% overall response rate did not reach the benchmark, oral administration of sotorasib once per day showed modest anti-tumour activity and manageable safety in these heavily pretreated chemorefractory patients. Sotorasib is under evaluation in combination with other therapeutics to increase potential activity and overcome potential resistance mechanisms. FUNDING: Amgen.