bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interventions for head and neck cancer survivors: A systematic review.
Authors: Margalit Danielle Nina , Salz Talya , Venchiarutti Rebecca L. , Milley Kristi , McNamara Mairead , Chima Sophie , Druce Paige , Nekhlyudov Larissa 
Published: June 2022

e24042 Background: Quality survivorship care includes cancer-related and general health care domains, including cancer surveillance and prevention of new cancers, management of psychosocial and physical late effects, health promotion/disease prevention, and management of chronic conditions. Survivors of head and neck cancer (HNC) have particularly complex unmet needs across all of these domains. We systematically reviewed interventions for HNC survivors to identify existing evidence and gaps in HNC survivorship care research. Methods: We performed a systemic review (PROSPERO ID: CRD42021269566) using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We searched MEDLINE, Embase, Emcare and PsycINFO for primary studies published in English between 2000 and 2021 to identify prospective studies for which interventions began after completion of cancer treatment and had a study endpoint ≥1 year after treatment completion. The population included adults treated with for HNC We used Covidence systematic review software to facilitate article screening and study selection. Two reviewers independently screened titles and abstracts followed by full texts for eligibility. Disagreements were resolved by consensus. Two reviewers critically appraised each selected study. Reviewers evaluated risk of bias with the Cochrane RoB 2.0 tool for randomized trials and the ROBINS-I tool for non-randomized studies. Due to the anticipated heterogeneity of included studies, narrative synthesis was used to summarize data. Results: The literature search identified 7395 studies; after applying inclusion and exclusion criteria, 28 studies were identified for critical appraisal: 13 randomized trials and 15 non-randomized studies. Most study interventions (n = 25) focused on surveillance and management of physical effects, including 13 studies that also targeted management of psychosocial effects. Four studies targeted the prevention and surveillance for recurrence and new cancers, and only one study addressed health promotion and disease prevention. Among the 13 randomized studies, 12 had a medium to high risk of bias, and 1 with a low risk of bias. The 15 non-randomized studies included 12 with a high risk and 3 with a medium risk of bias. Common sources of bias included lack of pre-planned sample size and power, lack of blinding of patients or assessors, heterogeneity in population, and attrition with incomplete follow-up. Conclusions: This systematic review and critical appraisal identified gaps in HNC survivorship intervention research targeting under-represented domains of the survivorship framework, and common challenges in study design that introduce risk of bias. To promote quality survivorship care for HNC survivors, scientifically rigorous intervention studies must address broader areas of focus.
LEAD BY EXAMPLE: Evaluation of an NCCN and ASCO guideline-based virtual weight loss and healthy lifestyle intervention on providers and staff members at a comprehensive cancer center.
Authors: Hansra Damien Mikael , Boodhoo Jacqueline , Warren Anya , Avinger Shanetia , Meiri Eyal 
Published: June 2022

e24045 Background: Obesity is a leading cause of preventable death in the United States. The incidence of most obesity associated malignancies are increasing. Novel interventions to combat the obesity epidemic are greatly needed. Here we investigate the effect of a virtual clinical intervention on medical providers & other medical staff at a comprehensive cancer center. Methods: Physicians (MD), nurses (RN), & other medical staff (MS) were enrolled in an IRB approved, prospective single arm clinical trial. We assessed the effect of NCCN & ASCO guideline recommendations for weight loss & healthy lifestyle on overweight (OW) & obese (OB) providers & medical staff. Primary outcome: to assess change in body mass index (BMI) over a 3-month (mo.) intervention. Secondary outcomes: To assess changes in nutrition and exercise habits over time b) evaluate other lifestyle factors over time: stress, self-image, barriers to weight loss. Participants (Pts) filled out two 16 question (Q) pre & post survey (at 1, 90 days) relating to study outcomes. The virtual intervention consisted of giving information & advice over 3 months: A comprehensive handout e-mailed on day 1 + Motivational/info e-mails q 2 weeks/3 mo. Statistical analysis: students' paired T test used to compare changes in weight & survey responses day 0-90. P- value α = 0.05. Inclusions: age > 18 yo males & females, MD, RN, ARNP, & MS who are OW (BMI > 25Kg/m2) or OB (BMI > 30Kg/m2). Exclusions: non-OW/OB, Pts with uncontrolled cardiovascular, pulmonary, orthopedic, or cerebrovascular disease, pregnancy. Results: 106 participants enrolled; 26 subjects completed study. Demographics: 6/26 = 23% (MD/ARNP), 12/26 = 46% (RN), 8/26 = 31% (MS). 4/26 = 15% male, 22/26 = 85% female, µ age 45 (25-67). 3/26 = 12% Asian, 5/26 = 19% Black, 18/26 = 69% White. 100% not Hispanic. µ BMI = 33.9 kg/m2 (25.1-44.5). Intervention: 26/26 (100%) Pts lost weight/3 mo., µ Δ kg = -5.2kg (p < 0.0001), µ Δ BMI = - 1.67 kg/m2 (p = 0.002). Survey results: Significant improvements were seen in: self-image (p = 0.0012), physical activity (p < 0.0001), healthy diet (p < 0.0001), days/week exercise (p = 0.0008), µ Δ minutes exercise/week = +65 min/week (p = 0.0046), decreased stress levels (p < 0.0001). Limitations: significant participant drop out seen. Conclusions: All participants who completed the study lost weight & improved healthy lifestyle parameters. To our knowledge this is the first all virtual clinical weight loss & lifestyle intervention executed. Also, this is the first weight loss & lifestyle intervention executed in providers. Our intervention was cost effective, easy to execute, & warrants further study in both medical staff & patient populations. Last, this novel virtual intervention is highly relevant during the covid 19 pandemic due to social distancing requirements.
Symptom profile of head and neck patients initiating care in a survivorship clinic.
Authors: Gilmore Katherine Ramsey , Hutcheson Kate A. , Chapman Patricia Hansberry , Bi Weiqi , Goepfert Ryan , Pytynia Kristen B , Rodriguez Maria Alma 
Published: June 2022

e24047 Background: After treatment, and at a time point of low risk of relapse, cancer patients at our institution transition to Survivorship Clinics (SC) that focus on wellness, late effects management, and psychosocial functioning in additional to cancer screening. We describe the self-reported symptoms of Head and Neck (HNC) survivors at the time of transition to SC, and the level to which these symptoms interfered with their function. Methods: Survivors reporting to their first in person SC appointment were assessed using the MD Anderson Symptom Inventory Head and Neck (MDASI–HN). This validated patient-reported outcome (PRO) instrument consists of 28 questions grouped into three subscales (core symptoms, disease specific symptoms, and interference items). Symptom severity is measured using a 0 to 10 scale (0 = not present, 10 = as bad as can be imagined). Descriptive statistics were used to characterize the sample. Percent of patients reporting moderate to severe symptoms (> = 4) are also noted. Results: This sub-analysis consisted of 377 patients seen for their initial transition visit to the survivorship clinic. Patients were mostly male (83%) and Caucasian (89%), with an average age of 63.8 years, and on average 41.5 months from diagnosis. Most common cancers were oropharynx (49%), oral cavity (33.7%), and larynx/hypopharynx (12.5%), nasopharynx (4.5%). Average symptom reports are presented in table. In rank order of prevalence (4% to 31% of patients), the top reported moderate to severe symptoms included dry mouth, swallowing/chewing, mucus, remembering, distress, and shortness of breath associated with moderated to severe interference in general activity in 8% of patients. Conclusions: HNC survivors report multiple persistent symptoms of moderate to high severity in a significant number, most commonly mouth dryness and swallowing and chewing difficulty. PROs can identify patients with high symptom burden, and lead in interventions to support the patients at their SC visit.[Table: see text]
The impact of NSCLC disease evolution and treatment on pre- and post-diagnosis weight loss and cachexia designation.
Authors: Iyengar Puneeth , Gilmore L Anne , Olaechea Santiago , Alvarez Christian , Ahn Chul , Infante Rodney E 
Published: June 2022

e24098 Background: While cancer cachexia is associated with increased morbidity/mortality, little is known about longitudinal weight changes and opportunities for intervention pre- and post-diagnosis in this patient population. We therefore aimed to characterize body weight trajectories pre- and post- non-small cell lung cancer (NSCLC) diagnosis in patients without and with cachexia. Methods: Data were retrospectively extracted for each patient pre- and post-diagnosis of NSCLC from inpatient and outpatient visits within the UT Southwestern Medical Center Healthcare System. 3830 participants were screened with a NSCLC diagnosis between May 2005 to December 2019. Of these, 661 patients had a body weight recorded at cancer diagnosis and at least one body weight pre-diagnosis. The primary outcome was weight change over time. Other measures included defining associations between weight change and tumor pathology, stage of disease, and other clinical characteristics. Results: NSCLC patients without cachexia at cancer diagnosis were weight stable up to 12-months pre-diagnosis (+1.0±0.3% body weight; p = 0.01). Weight loss post-diagnosis was driven by stage of disease (stage 1/2: 0.4±0.5% body weight vs. stage 3/4: 4.8±0.9% body weight p = 0.0008) and treatment with chemotherapy (p < 0.0001). NSCLC patients with cachexia at cancer diagnosis lost weight pre-diagnosis (8.8±0.5% body weight; p < 0.0001), with 25% of this weight loss occurring between 6- and 12-months pre-diagnosis. Assessing weight change over 12 months opposed to 6 months resulted in a 32% increase in NSCLC patients with cachexia at cancer diagnosis (p = 0.006). By 12-months post-diagnosis, 62% of surviving late-stage and 45% of early-stage NSCLC patients had met the criteria for cachexia. Patients on average remained free of weight loss for 150±6.4 days or had pre-cachexia for 146±7.2 days prior to transitioning to a more advanced stage of the syndrome. Conclusions: Significant weight loss in NSCLC patients initiated as far back as 12 months prior to a cancer diagnosis as opposed to a shorter 6-month interval currently used to define patients with cachexia. Therefore, detection of earlier weight loss should be prioritized in high-risk NSCLC screening candidates. Finally, advanced NSCLC patients develop cachexia post-diagnosis irrespective of previous weight history, highlighting the impact of treatment iatrogenicity and/or refractory disease on cachexia development.
Phase 2 trial of tucatinib plus trastuzumab deruxtecan in patients with HER2+ locally advanced or metastatic breast cancer with and without brain metastases (HER2CLIMB-04, trial in progress).
Authors: Krop Ian E. , Carey Lisa A. , Ramos Jorge , Chen Yiyi , Hamilton Erika P. 
Published: June 2022

TPS1111 Background: Tucatinib is an oral reversible small-molecule tyrosine kinase inhibitor highly selective for human epidermal growth factor receptor 2 (HER2). Tucatinib is approved in the US for use in combination with trastuzumab and capecitabine in adult patients with HER2+ metastatic breast cancer (MBC), with and without brain metastases, who have received ≥1 prior anti–HER2-based regimens in the metastatic setting. Trastuzumab deruxtecan (T-DXd), an antibody–drug conjugate (ADC) comprising a HER2-directed monoclonal antibody conjugated to a topoisomerase I inhibitor payload, is also approved in the US for patients with HER2+ MBC. In HER2+ breast cancer (BC) xenograft models, tucatinib increased the antitumor activity of a HER2-directed ADC comprising a HER2-directed monoclonal antibody conjugated with 8 exatecan moieties (T-Ex) when compared to T-Ex alone (Kulukian et al 2019). While significant advances have been made in the treatment of patients with HER2+ BC, treatment of metastatic disease remains a clinical challenge due to limited treatment options. Methods: HER2CLIMB-04 (NCT04539938) is a single-arm, open-label, multicenter, phase 2 study evaluating the efficacy and safety of tucatinib plus T-DXd in previously treated patients aged ≥18 years with unresectable, locally advanced, or metastatic (LA/M) HER2+ BC. Patients must have prior treatment with a taxane and trastuzumab (with or without pertuzumab) in the LA/M setting or progressed within 6 months after neoadjuvant or adjuvant treatment involving a regimen including a taxane and trastuzumab (with or without pertuzumab). Patients with brain metastases, including active brain metastases, may be enrolled. A safety lead-in portion of the study with 10 patients who were followed for at least 1 cycle has been completed. This portion of the study demonstrated a manageable safety profile so the trial will enroll approximately 60 response-evaluable patients (including the 10 patients from the safety lead-in), evenly distributed between patients with and without brain metastases. The primary endpoint is confirmed objective response rate (cORR) by investigator assessment per RECIST 1.1. Secondary endpoints are progression-free survival (PFS), duration of response (DOR), disease control rate (DCR) by investigator assessment per RECIST 1.1, overall survival, and safety. Exploratory endpoints will include cORR, PFS, DCR, and DOR by independent central review per RECIST 1.1, pharmacokinetic analyses, biomarker analyses, and changes in patient-reported outcomes. Efficacy and safety will be summarized with descriptive statistics. Enrollment in the US began in late 2020. Clinical trial information: NCT04539938.
A phase I trial of T-cell receptor gene therapy targeting KK-LC-1 for gastric, breast, cervical, lung and other KK-LC-1 positive epithelial cancers.
Authors: Norberg Scott , Von Euw Erika Maria , Parry Gordon , Highfill Steven , Franco Zulmarie , Gulley James L. , Hinrichs Christian S. 
Published: June 2022

TPS2678 Background: T cell receptor (TCR)-T cell therapy is an emerging cancer treatment strategy. Thus far, demonstration of clinical activity has been limited to a subset of solid tumors including melanoma, synovial cell sarcoma and HPV-associated cancer. It is estimated that metastatic epithelial cancers are responsible for approximately 90% of cancer deaths in the United States. The estimated 600,000 cancer deaths each year is driven largely by lung adeno- and squamous cell carcinoma and invasive breast cancer, which account for approximately 30% of all cancer-related deaths. Kita-Kyushu Lung Cancer Antigen 1 (KK-LC-1) is a cancer germline antigen with expression restricted to germ cells in adults and certain epithelial cancers including lung, breast, gastric and cervical. We identified a KK-LC-1 TCR from the tumor-infiltrating lymphocytes (TIL) of a patient with cervical cancer who had a complete tumor response to TIL therapy. The KK-LC-1 TCR was the most dominate clonotype in the infused TIL product and persisted in the peripheral blood following infusion, suggesting that it may have contributed to cancer regression in this patient. Methods: We are conducting a phase I cell dose escalation trial to test the safety and efficacy of KK-LC-1 TCR-T cell therapy in patients with metastatic KK-LC-1 positive epithelial cancer. Patients receive a lymphocyte depleting conditioning regimen followed by a one-time infusion of genetically engineered T cells expressing the KK-LC-1 TCR (KK-LC-1 TCR-T cells) and high-dose systemic aldesleukin. KK-LC-1 positivity is determined by RNAscope assay measuring the percentage of cancer cells expressing CT83 (gene encoding KK-LC-1) with a percentage of 25 or greater considered positive. Main inclusion criteria include HLA-A*01:01 allele, prior first-line therapy, ECOG of 0 or 1 and adequate organ and hematologic function. Main exclusion criteria include active major medical illness of the cardiovascular, respiratory or immune system, primary or secondary immunodeficiency and autoimmune disease. Participants will be entered in sequential dose levels and receive escalating doses of cells beginning at 1x108 and ending with 6x1010. Dose-limiting toxicities will be assessed during the first 30 days of cell infusion. The primary objective is to determine the maximally tolerated dose of KK-LC-1 TCR-T cells. Exploratory objectives include assessing the safety and efficacy of KK-LC-1 TCR-T cells and to conduct immunologic studies to understand and improve the administered treatment. Clinical trial information: NCT05035407.
A phase 1/2 study of RTX-224, an engineered red blood cell expressing 4-1BB ligand and membrane-bound IL-12, for the treatment of patients with select advanced solid tumors.
Authors: Spira Alexander I. , Johnson Melissa Lynne , Ren Ai , Sundaresan Varsha , Verdon Ines , Turka Laurence , Elloul Sivan 
Published: June 2022

TPS2680 Background: RTX-224 is a genetically engineered off-the-shelf, allogeneic red blood cell that expresses the costimulatory molecule 4-1BB ligand (4-1BBL) and cytokine interleukin-12 (IL-12) on the cell surface. The use of 4-1BB and IL-12 agonists for cancer immunotherapy has been limited due to systemic toxicities. Unlike agonist antibodies and recombinant cytokines, which are distributed systemically, Red Cell Therapeutics, such as RTX-224, are restricted to the vasculature and spleen, which may limit toxicities previously observed with agonist 4-1BB monoclonal antibodies and recombinant IL-12. RTX-224 is designed to be a broad immune agonist of both adaptive and innate responses that activates and expands effector and memory CD8+ and CD4+ T cells, cytotoxic natural killer (NK) cells and produces inflammatory cytokines and chemokines, leading to enhanced antigen presentation. In preclinical studies, the combined activation of both adaptive and innate immune responses by the murine surrogate of RTX-224 led to antitumor activity while the restricted biodistribution improved the safety profile. Methods: The RTX-224-01 study is a Phase 1/2, first-in-human, multi-center, dose-escalation and expansion study of RTX-224 in patients with relapsed or refractory urothelial cancer, squamous cell carcinoma of the head and neck, non-small cell lung cancer, triple negative breast cancer and cutaneous melanoma. Safety, tolerability, pharmacokinetics and pharmacodynamics and anti-tumor activity of RTX-224 will be assessed. Approximately 28 patients will be enrolled across dose level cohorts to identify the recommended Phase 2 dose (RP2D). The starting dose is 100 million (1x108) cells administered intravenously every 3 weeks (Q3W) and the dose will be escalated by half-log increments following a Bayesian logarithmic regression model (BLRM) with overdose control. Following RP2D selection, each of the 5 expansion cohorts will enroll approximately 20 patients. Pharmacodynamic and exploratory biomarker studies correlative to clinical response will be evaluated on peripheral blood and paired tumor biopsies. Multiple technologies will be employed to profile the innate and adaptive responses following RTX-224 treatment. The study is open and enrolling patients in Phase 1. Clinical trial information: NCT05219578.
A multicenter, open-label, phase 1a/b study of HC-7366, a modulator of integrated stress response (ISR) kinase GCN2 in subjects with advanced solid tumors.
Authors: Pelster Meredith , Torre Marcio , Kannan Geoffrey Sumithran , Gargano Michele Anne , Mattson Paulette , Rathmann Blaine , Bose Nandita , Iglesias Jose Luis 
Published: June 2022

TPS3179 Background: To survive harsh tumor microenvironments, cancer cells actively utilize ISR as an adaptive stress response and survival mechanism. General control nonderepressible 2 (GCN2), a serine-threonine kinase is essential for maintaining cellular homeostasis in amino acid stress conditions. HC-7366 is a novel, highly selective, and potent GCN2 kinase modulator. Single agent HC-7366 has demonstrated potent anti-tumor activity resulting in regression and complete responses in several pre-clinical tumor models. Methods: This is a first in human, multicenter, open label, Phase 1a/b dose escalation and expansion study to establish the maximum tolerated dose, evaluate safety and tolerability, and determine the recommended Phase 2 dose of daily oral dosing of HC-7366 in patients (pts) with advanced solid tumors. Up to 36 pts with squamous cell carcinoma of the head and neck (SCCHN), colorectal cancer (CRC), non-small cell lung cancer (NSCLC), or transitional cell carcinoma of the bladder (TCC) will be enrolled into Phase 1a; other solid tumors are eligible if selection criteria are met (capped at 50%). A 3+3 design will be employed and dose escalation determined by occurrence of dose limiting toxicities (DLT) within Cycle 1 (21 days). A Safety Monitoring Committee will review each cohort when the planned number of pts complete the DLT period. Six dose levels (10, 20, 40, 75, 125, 150 mg) of HC-7366 will be evaluated. Phase 1b will be an expansion of up to two Phase 1a dose levels and enroll 15 pts per cohort. Secondary endpoints include ORR, DOR, TTF, PFS, and OS. Pharmacokinetic data will be profiled. Exploratory objectives include evaluation of pharmacodynamic markers in tumor biopsies and immunophenotyping in blood samples. Main inclusion criteria include: SCCHN, CRC, NSCLC, TCC or other solid tumors; >1 radiologically measurable lesion per RECISTv1.1; >1 biopsiable lesion at baseline; no immune checkpoint inhibitor within 4 weeks (wks) of 1st dose; ECOG 0 or 1; <10% body weight loss in 4 wks before 1st dose & serum albumin >3 g/dL; and normal/adequately controlled pan-endocrine function. Main exclusion criteria include: autoimmune disease, organ transplant, retinitis or photosensitive skin disorders; history of interstitial lung disease or pneumonitis within 1yr; and overt or latent disorders of the exocrine pancreas. Formal hypothesis testing will not be performed. Descriptive statistics of parameters of interest will be presented by dose level and safety parameters will be summarized. The trial is sponsored by HiberCell, Inc. Approximately 9 US sites will participate. Clinical trial information: NCT05121948.