Patient Refusal Research Articles

Hospital Utilization of Stereotactic Body Radiation Therapy and Rates of Surgical Refusal

BackgroundIncreasingly, stereotactic body radiation therapy (SBRT) is used for patients unfit for or unwilling to undergo operation for early-stage non–small cell lung cancer. It remains unclear how SBRT utilization has influenced patient refusal of surgical resection. MethodsA retrospective cohort analysis was completed using the National Cancer Database for patients with T1/T2 N0 M0 lesions from 2008 to 2017. Facilities were categorized into tertiles by SBRT/surgery ratio for each year of analysis. Propensity score matching was used to compare rates of surgical refusal and rates of postrefusal receipt of SBRT. Multivariable regression analysis was performed to evaluate effect size. ResultsThe study included 129 901 patients; 63 048 were treated at low-tertile SBRT/surgery facilities, 41 674 at middle-tertile SBRT/surgery facilities, and 25 179 at high-tertile SBRT/surgery facilities. Patients refusing surgery at high SBRT/surgery facilities had fewer comorbid conditions and smaller tumors. Rates of SBRT after surgical refusal differed (low SBRT/surgery facilities, 17.2%; high SBRT/surgery facilities, 55.9%; P < .001). In a matched cohort of 76 636, surgical refusal differed (low SBRT/surgery facilities, 4.2%; high SBRT/surgery facilities, 6.0%; P < .001). On multivariable regression, treatment at a top-tertile SBRT/surgery facility was the largest risk factor for surgical refusal (odds ratio, 3.82 [3.53-4.13]; P < .001) and was most strongly associated with postrefusal receipt of SBRT (odds ratio, 6.11 [5.09-7.34]; P < .001). ConclusionsPatients treated at high SBRT–using facilities are more likely to refuse surgical resection and more likely to receive radiation therapy after surgical refusal. Further analysis is needed to better understand patient refusal of surgery in the setting of early-stage non–small cell lung cancer.

Effectiveness of a Patient Education Bundle on Venous Thromboembolism Prophylaxis Administration by Sex

IntroductionVenous thromboembolism (VTE) is a frequent cause of preventable harm among hospitalized patients. Many prescribed prophylaxis doses are not administered despite supporting evidence. We previously demonstrated a patient-centered education bundle improved VTE prophylaxis administration broadly; however, patient-specific factors driving nonadministration are unclear. We examine the effects of the education bundle on missed doses of VTE prophylaxis by sex. MethodsWe performed a post-hoc analysis of a nonrandomized controlled trial to evaluate the differences in missed doses by sex. Pre-intervention and intervention periods for patients admitted to 16 surgical and medical floors between 10/2014-03/2015 (pre-intervention) and 04/2015-12/2015 (intervention) were compared. We examined the conditional odds of (1) overall missed doses, (2) missed doses due to patient refusal, and (3) missed doses for other reasons. ResultsOverall, 16,865 patients were included (pre-intervention 6853, intervention 10,012), with 2350 male and 2460 female patients (intervention), and 6373 male and 5682 female patients (control). Any missed dose significantly reduced on the intervention floors among male (odds ratio OR 0.55; 95% confidence interval CI, 0.44-0.70, P < 0.001) and female (OR 0.59; 95% CI, 0.47-0.73, P < 0.001) patients. Similar significant reductions ensued for missed doses due to patient refusal (P < 0.001). Overall, there were no sex-specific differences (P-interaction >0.05). ConclusionsOur intervention increased VTE prophylaxis administration for both female and male patients, driven by decreased patient refusal. Patient education should be applicable to a wide range of patient demographics representative of the target group. To improve future interventions, quality improvement efforts should be evaluated based on patient demographics and drivers of differences in care.

Adjuvant chemotherapy after radical cystectomy: Do all patients who need chemotherapy after surgery actually receive it?

Compliance with the guideline recommendations for neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer is incomplete. The adjuvant chemotherapy approach has the advantage of pathology-based decision-making, allowing for patient selection. In addition, radical surgery is not delayed and treatment-related toxicity does not impair surgical fitness. The proportion of patients who completed chemotherapy after cystectomy among those who were fit and in need of treatment were evaluated. The reasons for not completing adjuvant chemotherapy were determined. We retrospectively evaluated all patients who had undergone radical cystectomy at our center over the last 7 years. Indications for adjuvant chemotherapy included pathological T > 2, any node+, or surgical margin involvement. Only patients who were fit for chemotherapy before surgery were included in the study. Of the 52 patients with muscle-invasive bladder cancer, 14 received neoadjuvant chemotherapy or unfit for chemotherapy were excluded. Of the remaining 38 patients, 14 (37%) had bladder-confined cancers and did not require additional chemotherapy. Of the 24 patients who needed chemotherapy and were fit to receive it, 8 patients completed treatment (33%), and 3 discontinued treatment due to toxicity. Twelve patients (50%) declined chemotherapy, whereas 1 patient became unfit for chemotherapy after surgery. While the adjuvant chemotherapy approach could save unnecessary treatment in 37% of patients, two-thirds of those who needed chemotherapy did not complete it. Patient refusal was the primary reason for not receiving treatment.

Observation and Patients' Perceptions of Incorporating Their Photograph Into the Electronic Health Record.

Wrong-patient errors are common and have the potential to cause serious harm. The Office of the National Coordinator for Health Information Technology Patient Identification SAFER Guide recommends displaying patient photographs in electronic health record (EHR) systems to facilitate patient identification and reduce wrong-patient errors. A potential barrier to implementation is patient refusal; however, patients' perceptions about having their photograph captured during registration and integrated into the EHR are unknown. The study was conducted in an emergency department (ED) and primary care outpatient clinic within a large integrated health system in New York City. The study consisted of 2 components: (1) direct observation of the registration process to quantify the frequency of patient refusals and (2) semistructured interviews to elicit patients' feedback on perceived benefits and barriers to integrating their photograph into the EHR. Of 172 registrations where patients were asked to take a photograph for patient identification, 0 refusals were observed (ED, 0 of 87; primary care outpatient clinic, 0 of 85). A convenience sample of 30 patients were interviewed (female, 70%; age ≥55 years, 43%; Hispanic/Latino, 67%; Black, 23%). Perceived benefits of integrating patient photographs into the EHR included improved security (40%), improved patient identification (23%), and ease of registration (17%). A small proportion of patients raised privacy concerns. Patient refusal was not found to be a barrier to implementation of patient photographs in the EHR. Efforts to identify and address other potential barriers would help ensure that the highest proportion of patients has photographs in their medical record.

Wide-awake local anesthesia for open rotator cuff repair: A case report.

Introduction and importanceImproper treatment of rotator cuff tear might result in progression of tear and deterioration of patient function. The rotator cuff tear can be managed conservatively in most cases however surgical treatment is inevitable in persistent patients.Presentation of caseA 45-year-old woman presented to our clinic with shoulder pain and restricted range of motion following a fall from a height three months before the current presentation. Due to the lack of favorable response to conservative treatment and the fact that rotator cuff rupture was traumatic, she became a candidate for rotator cuff repair surgery. Due to financial issues and the patient's refusal of undergoing general anesthesia we considered the WALANT technique. Prior to surgery, we explained the whole procedure to the patient, referring to its pros and cons.Clinical discussionThe WALANT procedure is a relatively recent technique that has become widespread in orthopedic surgery in the past decade. The advantages of the WALANT technique are that it is simple, feasible, and safe and that the analgesic is adequate during the operation and for the first few hours afterward (5). Concerns with this method include patient discomfort and pain during surgery, which can be managed by educating the patient and minute-by-minute explanation during the procedure.ConclusionWe advocate open rotator cuff repair with the WALANT approach as an effective, cost-saving, safe, simple, and quick alternative to general and regional anesthesia for certain patients or with limited anesthetic resources.Level of evidenceV

What predetermines the therapeutic tactics of a physician in the treatment of dementia? Results of a survey of Russian physicians

In order to study the point of view of doctors supervising patients with dementia regarding the methods and tactics of treating diseases that occur with severe cognitive impairment, their experience in the use of drugs and criteria for choosing a drug for long-term treatment of dementia, an online survey of 197 specialists was conducted.The majority of Russian physicians surveyed prefer basic therapy for dementia, while the main criteria for choosing a drug for long-term therapy are effectiveness and safety of the drug. Despite the absence of drugs capable of complete curing of dementia, Russian doctors have certain expectations and goals when prescribing therapy, in particular, the hope for the longest possible preservation of the quality of life and capacity of patients, as well as slowing down the progression of the disease. 90% of respondents consider it necessary to continue (and even start) therapy even at a severe stage, despite the depletion of the effect. Memantine has become the main drug of choice in different regions of Russia as a drug with a wide range of registered indications, the fewest side effects and a low percentage of patient refusals.

Trancatheter Aortic Valve Implantation in the Treatment of Heyde's Syndrome: A Case Report

Calcified aortic stenosis is the most common valvulopathy of the elderly. Its association with angiodysplasia and digestive bleeding is known as Heyde syndrome. This clinical case highlights the importance of the diagnosis of this syndrome whose complications can be fatal. The cessation of gastrointestinal bleeding is often remarkable after aortic valve replacement. Transcatheter aortic valve implantation (TAVI) can represents a good alternative to surgical valve replacement, especially in patients with high surgical risk. We report a case of 62-year-old patient, admitted for management of global cardiac decompensation on a tight aortic stenosis, confirmed by transthoracic echocardiography as well as a few episodes of syncope. He had a history of repeated lower digestive hemorrhages that required several transfusions. The evolution was marked by the appearance of heavy rectal bleeding on cecum angiodysplasia lesions confirmed by colonoscopy. The association of digestive bleeding and aortic stenosis raised the diagnosis of Heyde syndrome. An assay of von Willebrand factor (vWF) antigen, vWF binding collagen activity and their ratio confirmed a qualitative deficiency of vWF type 2A. The proposed treatment was TAVI because of the high surgical risk and the patient's refusal of the surgery. The evolution at 1 month post TAVI was marked by the improvement of hemostatic parameters related to the vWF and the disappearance of cardiac symptomatology. The cessation of gastrointestinal bleeding in Heyde's syndrome is conditioned by percutaneous aortic valve replacement in the high-risk surgical subject with a good clinical and biological evolution.

Why the Emergency Department Visit Decreased during the Covid-19 Pandemic? Case Study in Hospital, Malang Regency

During the 2020 Covid-19 pandemic, emergency department experienced a drastic decreasing visit that could disrupt hospital financing. This study was conducted to identify the root cause of the declining ED visit. The study was conducted descriptively from FGD involving eight selected respondents, surveys on 83 patients regarding service perceptions and satisfaction, as well as secondary data on visits and requests of discharge against medical advice. The results showed that the decreasing visit was due to the patient's refusal on treatment in the isolation room, the staff's skills to provide communication and education, and the potential of cooperation termination from partners. Those refusals were due to the patient's perception of hospital services and the differences in patient needs on health protocols resulted from the lack of individual and organizational communication. Hospitals need to build staff's skills in communication and education as well as intensive communication strategies with partners to communicate policies and service system changes so that trust and a positive image are built.

Burden of Cancer and Utilization of Local Surgical Treatment Services in Rural Hospitals of Ethiopia: A Retrospective Assessment from 2014 to 2019.

Global cancer estimations for Ethiopia announced 77 352 new cases in 2020 based on the only population-based registry in Addis Ababa. This study characterizes cancer patients in rural Ethiopia at 8 primary and secondary hospitals between 2014 and 2019. All clinically or pathologically confirmed cancer cases that were diagnosed between 1 May 2014 and 29 April 2019 were included. A structured data extraction tool was used to retrospectively review patients' charts and descriptive analysis was done. A total of 1298 cancer cases were identified, of which three-fourths were females with a median age of 42 years. Breast (38%) and cervical (29%) cancers were the most common among females, while prostate (19%) and oesophageal cancers (16%) were the most common among males. Only 39% of tumors were pathologically confirmed. Nearly two-thirds of the cases were diagnosed at an advanced stage. Surgery was the only accessible treatment option for more than half of the cancer patients, and systemic treatment (except endocrine) was rarely available. One in 5 patients did not receive the recommended surgical procedure, half due to patient refusal or lack of the patient returning to the hospital. The pattern of cancer diagnoses in rural hospitals shows an exceptionally high burden in women in their middle-ages due to breast and cervical cancers. Advanced stage presentation, lack of pathology services, and unavailability of most systemic treatment options were common. The surgery was offered to nearly 60% of the patients, showing the significant efforts of health workers to reduce sufferings.

Patterns of Emergency Medical Transport for Suspected Acute Stroke, Acute Myocardial Infarction, and Other Diagnoses During the COVID‐19 Pandemic: A Retrospective Analysis of a Large Hospital‐Based Emergency Medical Services Agency

Patterns of Emergency Medical Transport for Suspected Acute Stroke, Acute Myocardial Infarction, and Other Diagnoses During the COVID‐19 Pandemic: A Retrospective Analysis of a Large Hospital‐Based Emergency Medical Services Agency

Incomplete mole in term pregnancy: a case report and literature review

A clinical case of a 24-year-old female is presented, which by first-trimester obstetric ultrasound data suggestive of an incomplete mole is detected, first-trimester screening is performed, reporting a fetus without structural alterations, pregnancy interruption is offered, the same as the patient refuses, pregnancy is continued until the end of 37 weeks of gestation; where a fetus is obtained phenotypically without structural malformations.

Intraoperative Parameters of Comminuted Proximal Humerus Fractures: A Comparison Between Deltoid-Split and Deltopectoral Approaches.

Background and objectiveMany controversies exist in the literature regarding proximal humerus fractures treated with various surgical procedures. The chosen approach decides the level of comfort with which the surgeon can perform a particular surgery in orthopedics and the amount of reduction a surgeon can bring to a fractured bone. The purpose of this study was to compare variables such as time taken for surgery, achievement of reduction, and intraoperative blood loss between the two most frequently employed surgical approaches for proximal humerus in comminuted fractures: the deltoid-split (DS) approach and deltopectoral (DP) approach.MethodsAll patients with Neer III and IV types proximal humerus fractures treated with Proximal Humeral Interlocking System (PHILOS) plating from 2017 to 2020 were invited to participate in the study. The exclusion criteria were as follows: Neer type I and II fractures, pre-existing limb pathology, patient refusal or patient being unfit for surgery, and patient requiring a different modality of treatment like external fixator and pinning. After obtaining consent, the dark envelope method was used to randomize patients into one of the two treatment methods. The variables analyzed were time taken for the surgery, intraoperative blood loss, anatomical reduction in immediate postoperative X-ray, and complications. The results were analyzed and findings were recorded.ResultsA total of 42 patients were randomized into the two groups (22 DS, 20 DP; mean age of 44.85 years for DS and 49.61 years for DP). In terms of age, gender, and Neer fracture classification, the groups were comparable. The average blood loss estimated was less in the DS group compared to the DP group; however, the difference was not statistically significant. Intraoperative time was not significantly different between the DS and the DP groups. The surgeons were able to achieve a significantly higher anatomical reduction in the immediate postoperative X-ray with the DP approach compared to the DS approach. The complications (two in DS and two in DP) in either approach were equal in number although all of them were unique.ConclusionsThe proximal humerus fracture treatment with a PHILOS plate is considered to be a reliable option using either of the described approaches. Based on our findings, the choice of the approach has no impact on surgical time and blood loss. However, patients who were operated on with the DP approach fared better in terms of achieving reduction as assessed by immediate postoperative X-ray owing to limited exposure distally limited by the axillary nerve.

Primary intra-ventricular hemorrhage in 33-year-old man: a case report

The aim of the study was to provide insight into cases of primary intra-ventricular hemorrhage caused by arterial venous malformations. A 33-year-old man visited the emergency room and admitted that he had a chief complaint of headache for the last 7 days. Neurological clinical examination only found nuchal rigidity. The CT scan of the head showed intra-ventricular hemorrhage and the CTA results showed an AVM with a left occipital nidus with arterialization of the posterior cerebral artery. One day before the DSA was performed, the patient had a seizure and based on a repeat CT scan, the bleeding spread to the parenchyma. The patient refused decompression and decided to go home after his condition stabilized and his complaints improved with anti-edema treatment. A repeat DSA action was planned but the patient had financial problems. Primary intra-ventricular hemorrhage occurs when the nidus arterial venous malformation is adjacent to the ventricle although this is only 7% of all cases of primary intra-ventricular hemorrhage. In the case of primary intra-ventricular hemorrhage, complications need to be wary of when hydrocephalus appears. In addition, digital subtraction angiography should be performed prior to endovascular surgery as the main modality of therapy. Arterial venous malformation can be one of the causes. Digital angiography and Endovascular measures should be performed in this patient to prevent further complications. However, the refusal of the patient and family until the time of this case report was made is a separate obstacle in the diagnostic and therapeutic process.

Why do Patients Refuse Pre-Prosthetic Procedures? A Qualitative Study in a Private Sector Dental Teaching Institute

Objective: To explore the factors leading to patient non-compliance toward pre-prosthetic mouth preparation.&#x0D; Study Design: Qualitative exploratory study.&#x0D; Place and Duration of Study: Prosthodontic Department of Islamabad Dental Hospital, Bara khau Islamabad Pakistan, from May to Jul 2020.&#x0D; Methodology: Semi-structured interviews were conducted from purposively selected fifteen partially dentate patients who were advised but had refused to get pre-prosthetic mouth preparation. Five content experts validated interview questions. After thematic analysis, the authors developed a consensus regarding themes and subthemes of factors that cause noncompliance of patients toward pre-prosthetic mouth preparation.&#x0D; Results: Eight themes emerged. Patients were afraid of extraction and scaling and were concerned about cross-infection control, and they were short of time due to busy schedules and lengthy procedures. Few diabetic patients could not go for extraction of their teeth immediately. Patients also refused due to financial constraints and lack of awareness regarding treatment protocols. Some believe myths that removing the teeth results in other diseases such as cancer. Few quoted previous bad dental experiences and were not willing for any pre-prosthetic procedure. In addition, patients were not satisfied with the treatment plan and the associated treatment cost.&#x0D; Conclusion: Fear or anxiety related to extraction or scaling, time and financial constraints, fear of delayed wound healing, and improper guidance regarding treatment protocols were central factors in refusing pre-prosthetic procedures. Patient counselling must be done regardless of patient refusal, and patient concerns should be addressed.

Comparison of postoperative back pain between paramedian and midline approach for thoracic epidural anesthesia.

BackgroundThe development of back pain following epidural analgesia is one reason for patient refusal of neuraxial analgesia. The primary endpoint of this study was to compare the incidence and severity of back pain following midline and paramedian epidural technique. The secondary endpoint was to identify the risk factors associated with the occurrence of back pain.MethodsThis prospective randomized study included 114 patients receiving thoracic epidural catheterization for pain management following upper abdominal or thoracic surgery. Patients were allocated to either the midline or the paramedian group by computer-generated randomization. An investigator who was blinded to the patient group interviewed patients at 24, and 48 h, and 3–5 days after surgery about the existence of back pain and its severity.ResultsThe total incidence of back pain following epidural anesthesia was 23.8% in the midline group and 7.8% in the paramedian group. The numerical rating scale of back pain was not different between the two groups at 24 h and 4 days after surgery. The paramdian technique was associated with a lower incidence of back pain than the midline technique (95% confidence interval 0.05–0.74, odds ratio 0.2, P < 0.01). However, the number of attempts, surgical position, body mass index, and duration of surgery were not associated with back pain.ConclusionsThis study showed that the midline group of thoracic epidural analgesia demonstrated higher incidence of back pain than the paramedian group. However, the pain was mild in intensity and decreased with time in both groups.

Determinants of Patient Refusal of Postoperative Radiation Therapy in Sinonasal Squamous Cell Carcinoma.

Objectives Although adjuvant radiotherapy may be indicated in patients with sinonasal squamous cell carcinoma (SNSCC) following primary surgery, some patients choose to forgo recommended postoperative radiation therapy (PORT). This study aimed to elucidate factors associated with patient refusal of recommended PORT in SNSCC and examine overall survival. Methods Retrospective analysis of patients with SNSCC treated with primary surgery from the National Cancer Database diagnosed between 2004 and 2016. A multivariable logistic regression model was created to determine the association between clinical or demographic covariates and likelihood of PORT refusal. Unadjusted Kaplan-Meier estimates, log-rank tests, and a multivariable Cox proportional hazard model were used to assess overall survival. Results A total of 2,231 patients were included in the final analysis, of which 1,456 (65.3%) were males and 73 (3.3%) refused recommended PORT. Patients older than 74 years old were more likely to refuse PORT than those younger than 54 (odds ratio [OR] 3.43, 95% confidence interval [CI]: 1.84-6.62). Median survival among the entire cohort, those who received recommended PORT, and those who refused PORT was 83.0 months (95% CI: 74.6-97.1), 83.0 months (95% CI: 74.9-98.2), and 63.6 months (95% CI: 37.3-101.4), respectively. Refusal of PORT was not associated with overall survival (hazard ratio: 0.99, 95% CI: 0.69-1.42). Conclusions PORT refusal in patients with SNSCC is rare and was found to be associated with several patient factors. The decision to forgo PORT is not independently associated with overall survival in this cohort. Further study is required to determine the clinical implications of these findings as the treatment decisions are complex.

CBTp for Schizophrenic and Schizoaffective Patients in a Forensic Psychiatric Setting: A Retrospective Audit

AimsCBTp is a clinically validated treatment for psychosis with meta-analyses showing beneficial effects for both positive and negative symptoms. CBTp is recommended by NICE for treatment of schizophrenia and psychosis. The aims of this audit were (1) To determine whether patients with schizophrenia or schizoaffective disorder had been offered CBTp as part of their treatment. (2) To determine if patient who were offered CBTp completed the recommended 16 minimum sessions. (3) To identify barriers to the offering and completion of CBTp. (4) Based on the audit findings, provide recommendations to assist in the utilisation of CBTp in the forensic psychiatric setting.MethodsA retrospective audit was carried out on 30 patients aged 18 years and older from a medium security forensic hospital, Liverpool UK. Patients included had a diagnosis of schizophrenia (F20) or schizoaffective disorder (F25). 26 male patients and 4 female patients were included in the audit, who were inpatients between 01/01/21 and 01/01/22.Data regarding the offering and completion of CBTp was collected from the electronic health system records and cross-referenced with the psychology team's internal data collection system to ensure that aims (1) and (2) could accurately be assessed and compared with NICE recommendations. Barriers to the offering and completion of CBTp were also documented and categorised into specific groups, with recommendations based on these findings being provided.ResultsThe audit found that 68% (19/28) of patients were offered CBTp, with 85% (11/13) of these patients going on to complete the recommended 16 minimum sessions of CBTp. Barriers to the offering of CBT included patients not being mentally well enough of psychological therapies (7/9) and being engaged in other psychological therapies (2/9). The barrier towards completion of 16 sessions of CBTp was patient refusal (2/2).ConclusionImplementation of CBTp for all patients with schizophrenia or schizoaffective disorder fell below NICE recommendations that all patients with psychosis should be offered CBTp and completed for at least 16 sessions. However, improvements have been made from previous similar studies, demonstrating a positive trend towards greater levels of psychotherapeutic interventions with schizophrenic and schizoaffective patients. Appropriate reasons for non-compliance were identified for all patients who were not offered CBTp and patient refusal was identified as an obvious barrier to CBTp completion. A framework for implementation will be recommended with an aim to improve patient compliance and overall health outcomes.

Nodal surveillance and adjuvant therapy in sentinel lymph node-positive melanoma patients.

e21586 Background: Since the publication of the Multicenter Selective Lymphadenectomy Trial-II (MSLT-II) in 2017, completion lymph node dissection (CLND) for sentinel lymph node (SLN)-positive patients has mainly been deferred for ultrasound surveillance of the nodal basin. Additionally, there is now widespread use of adjuvant therapy in these patients. However, CLND was required for the major adjuvant therapy trials, therefore information on recurrence patterns in SLN-positive patients receiving adjuvant therapy without CLND is limited. Methods: In this retrospective cohort study of patients with SLN-positive melanoma identified from 2017 to 2021 at a single institution, the primary aim was to evaluate the incidence of local, nodal, in-transit, and distant recurrence in patients receiving adjuvant therapy with nodal surveillance compared to nodal surveillance alone. Method of detection of recurrence, compliance with ultrasound surveillance, and clinicopathologic risk factors were also assessed. Chi-square tests were used to evaluate for any associations between clinicopathologic characteristics, initial location of recurrence, and receipt of adjuvant therapy. Results: Of 157 SLN-positive melanoma patients identified, 21 (13%) received CLND and 13 (8%) had insufficient follow-up information for inclusion. Among 123 eligible patients (mean 55 years, 54% male), the median follow-up time was 24.5 months during which 33 (27%) patients recurred. Of 13 patients with isolated nodal recurrence, three were detected by ultrasound alone, five were detect by CT alone, and five were detected by both CT and ultrasound (Table). 90 (73%) patients in the cohort received adjuvant therapy (92% anti-PD1, 6% BRAF/MEK, 2% anti-CTLA4). The main reasons for exclusion of adjuvant systemic therapy were minimal nodal disease or patient refusal. The average time to recurrence was 13.4 months. There were no significant differences in recurrence rates (p = 0.49) or location of initial recurrence (p = 0.64) by receipt of adjuvant therapy. 29 (24%) patients missed more than one ultrasound. Ultrasound surveillance was most frequently missed due to clinician omittance or patient distance to clinic. Conclusions: In our cohort of SLN-positive melanoma patients, the majority received adjuvant anti-PD1 immunotherapy and were followed in surveillance without CLND. There was no significant difference in recurrence patterns based on receipt of adjuvant therapy and a quarter of nodal recurrences were detected by ultrasound alone. Our results support the use of ultrasound surveillance in addition to cross-sectional imaging to monitor for recurrence in these high-risk patients.[Table: see text]

Phase 1 study of KT-333, a targeted protein degrader, in patients with relapsed or refractory lymphomas, large granular lymphocytic leukemia, and solid tumors.

TPS3171 Background: The signal transducer and activator of transcription 3 (STAT3) protein is activated by cytokines and growth factors resulting in tumor growth and promotion and hindering antitumor immunity. Approximately 70% of human cancers including both hematological malignancies and solid tumors exhibit increased levels of phosphorylated STAT3 (pSTAT3). There is evidence of constitutive activation of STAT3 through genetic mutations or aberrant cellular signaling pathways in tumors such as large granular lymphocytic leukemia (LGL-L), peripheral T-cell lymphoma (PTCL), and cutaneous T-cell lymphomas (CTCL). Hyperactivation of STAT3 has been reported in a variety of solid tumors. In several of these cancers, the levels of pSTAT3 and/or activated STAT3 have been shown to correlate with poor clinical prognosis. As with other transcription factors, selective inhibition of STAT3 has been proven to be difficult with conventional therapeutic approaches. KT-333 is a potent highly selective, heterobifunctional small molecule degrader of STAT3. In preclinical studies, durable tumor regressions were seen with weekly KT-333 administration in STAT3-dependent T cell lymphomas, and antitumor activity was seen in solid tumors in combination with anti-PD1 (ASH 2021, SITC 2021). Methods: KT-333 is being evaluated in an open-label, dose escalation (Phase 1a, n = 40) study in patients with lymphomas relapsed or refractory (R/R) to at least two prior systemic treatments or for whom standard therapies are unavailable. Dose escalation will be conducted by accelerated titration followed by a 3+3 design in ascending doses of intravenous KT-333 administered once weekly in 28-day cycles to evaluate safety and define the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) (primary endpoint). Secondary endpoints include pharmacokinetics (PK) in plasma and urine and preliminary pharmacodynamic effects (PD) of KT-333 using blood (peripheral blood mononuclear cells [PBMCs], plasma/serum) and tumor tissue. After confirming the MTD/RP2D in patients with lymphoma, patients with advanced solid tumors will be enrolled in a separate Phase 1a cohort at the MTD/RP2D. In Phase 1b (n = 80), patients with PTCL, CTCL, LGL-L (T-cell LGL-L or chronic lymphoproliferative disorder of natural killer-cells), or solid tumors R/R to at least one prior systemic standard of care treatment or for whom standard therapies are not available, will be enrolled in separate 20 patient cohorts. This will further characterize safety, PK, PD and evaluate the clinical activity of KT-333. Treatment with KT-333 will continue until disease progression, unacceptable toxicity, or patient refusal. KT333-TL-101 began enrolling in January 2022. Clinical trial information: NCT05225584.

Short-term efficacy of furmonertinib in treatment of NSCLC patients with EGFR exon20 insertion.

e21063 Background: EGFR is a key driver gene of lung cancer, in which exon 20 insertion (Ex20ins) mutation accounts for about 1-5%. However, the first- and second-generation EGFR-TKI had poor efficacy on patients with Ex20ins mutation (ORR = 6.9%, mPFS = 1.9 months, mOS = 12.9 months, DCR = 44.8%). Our study retrospectively observed the short-term efficacy and safety of furmonertinib in Chinese NSCLC patients with EGFR Ex20ins mutation. Methods: The study retrospectively collected 15 NSCLC patients with EGFR Ex20ins mutant who were treated in two medical institutions in Changzhou City, Jiangsu Province from April 2021 to December 2021. All patients received targeted therapy with furmonertinib. The last follow-up time was December 30, 2021. All patients received 160 mg furmonertinib orally until disease progression, drug intolerance, patient refusal or death. EGFR Ex20ins mutation was confirmed by ARMS or next generation sequencing (NGS). The patient's gender, age, score of Eastern Cooperative Oncology Group (ECOG), smoking history, pathological type, tumor stage, gene status and other basic clinical characteristics and adverse events (AES) were collected. The clinical efficacy was evaluated according to RECIST version 1.1, and the adverse events were evaluated according to the NCI-CTCAE version 5.0. SPSS 25.0 software was used to record and analyze the data. Results: All 15 patients had received ≥2 lines of therapy. The median age was 62 (25-80) years old, and there were 8 male patients (53.3%). Most patients had no smoking history (13 cases, 86.7%). ECOG score was mostly 1 (13 cases, 86.7%). In 15 patients, we found 10 different EGFR Ex20ins variants, among which p.A767_V769dup (n = 3) and p.A767_V769dup (n = 4) were more common. By the end of follow-up, 15 patients had completed at least one efficacy evaluation, and all had different degrees of tumor regression. No patient reached CR, 8 patients had PR and 7 patients had SD. This preliminary efficacy data showed that the overall ORR was 53.5% and DCR was 100%. No grade 3 or above adverse events were observed. The 3-months PFS rate was 100%. Conclusions: The results of this study in ≥2 lines patients treated with twice the conventional dose had a good curative effect (compared with 3 times of conventional dosage in FAVOUR study), which provided more treatment options for NSCLC patients in multiple lines of treatment and could alleviate part of their economic pressure, but the PFS and OS data still need further follow-up and verification of a larger sample size. The overall findings suggested that furmonertinib is a third generation EGFR-TKI with good efficacy and acceptable safety. Given the heterogeneity of EGFR Ex20ins mutation, the efficacy of targeted therapy may vary in different mutation types and requires further investigation.