Solid Organ Malignancies Research Articles

Ziltivekimab for anemia and atherosclerosis in chronic kidney disease: a new hope?

Anemia of chronic kidney disease is a multifactorial condition secondary to various etiologies, including nutritional deficiencies, chronic inflammation, erythropoietin deficiency or resistance, bone marrow suppression, iron deficiency and adverse drug effects. The major therapeutic intervention for anemia among chronic kidney disease patients is erythropoiesis-stimulating agents. However, a limitation of erythropoiesis-stimulating agents is the risk for thromboembolic events, hypertension, seizures, solid organ malignancies and hyporesponsiveness. A novel interleukin-6 monoclonal antibody, ziltivekimab, has been evaluated for managing anemia in chronic kidney disease patients in pilot clinical trials with promising outcomes, including an improvement in hemoglobin levels and reduction of inflammatory parameters. These trials have shown that ziltivekimab does not increase the risk for cytopenia or infectious complications as has been described for other interleukin-6-targeting monoclonal antibodies, like tocilizumab. Furthermore, potentially beneficial effects on serum lipid profile have been reported, leading to the hypothesis of a favorable impact of the drug on atherosclerotic complications. In addition, ziltivekimab has shown efficacy in improving anemia parameters, including hemoglobin levels and iron studies. Ziltivekimab deserves full scale clinical development, and to this aim, large-scale clinical trials are under way.

8270 A Rare Case Of PTHrP Induced Severe Hypercalcemia Secondary To Squamous Cell Carcinoma Of Tongue

Abstract Disclosure: N. Vennelaganti: None. S. Vennelaganti: None. K. McCowen: None. Background: PTHrP-mediated hypercalcemia is often associated with solid organ malignancies and indicates a poor prognosis. The occurrence of this condition due to SCC of the head and neck, particularly of the tongue, is uncommon. This case report aims to shed light on this rare clinical presentation. Clinical Case: A 70-year-old woman with a history of tobacco use disorder, alcoholic liver cirrhosis, and a chronic fungal prosthetic joint infection presented with altered mental status and acute kidney injury. Laboratory tests revealed a corrected calcium level of 15.4 mg/dL and suppressed PTH of 3 pg/mL, indicating non-PTH-dependent hypercalcemia. Differentials considered included malignancy, multiple myeloma, 1,25 OH Vit D mediated hypercalcemia via fungal granuloma formation, and immobilization. Diagnostic evaluation revealed normal levels of 25 hydroxy Vitamin D ie: 54 ng/mL, normal kappa to lambda ratio suggestive of negative myeloma screen, normal TSH of 2.81 uIU/mL, and a low 1,25 OH Vit D level ie: 11.4 pg/mL (Ref range: 19.9-79.3 pg/mL). An elevated PTHrP concentration of 9.7 pmol/L (ref range 0-3.4 pmol/L) was noted. CT angiography performed for stroke evaluation incidentally discovered a base of tongue mass, which was difficult to appreciate on exam due to obtundation. A biopsy confirmed SCC of the tongue, and she was determined to be Stage IVA. The patient's hypercalcemia was determined to be secondary to PTHrP production from the tongue SCC compounded by immobilization. She was treated with IV fluids and subcutaneous calcitonin, normalizing her calcium levels over 20 days. IV Bisphosphonates were held inpatient due to poor renal function. She was seen by oncology and determined to not be fit for surgical management or chemotherapy. Radiation therapy was advised for management and patient was discharged. While awaiting her outpatient radiation treatment, the patient had another episode of altered mental status and was found to have a serum calcium of 16.4 mg/dL. She was managed with IV fluids, calcitonin and IV Zoledronate which improved her serum calcium. She has since been receiving monthly IV Zometa with oncology for hypercalcemia of malignancy. She was recently readmitted with severe oropharyngeal and pharyngeal dysphagia and has received a PEG tube for feeding. She is still pending radiation therapy for SCC tongue. Conclusion: Initially, during the workup of this case, we believed her hypercalcemia was likely immobilization-induced, but thorough investigation and the elevated PTHrP levels steered us towards malignancy as a potential etiology. This case is an example of an occult malignancy which lead to severe hypercalcemia. It also contributes to the understanding of hypercalcemia in cancer patients and highlights the rare association of SCC of the tongue with PTHrP-mediated hypercalcemia . PTHrP secreting SCC of head and neck are typically associated with a poor prognosis. Presentation: 6/2/2024

Missed Opportunities for use of Advanced Care Planning and Palliative Care in Open Aortic Surgery

Major vascular surgery, including open aortic procedures, is associated with having a 30-day mortality rate greater than 6% and a perioperative complication rate greater than 50%. Published literature suggests that patients undergoing high-risk procedures benefit from having a care plan in place to not only maximize quality of life but also to ensure medical interventions align with care goals. Currently, there is a paucity of published data on the prevalence of goals of care conversations, advance care planning documentation, and palliative care evaluations in patients undergoing high-risk vascular operations. A retrospective chart review of all patients who underwent open aortic surgery at a tertiary care academic medical center from July 2014 to March 2023 was performed. Patient demographics, comorbidities, type and timing of advanced care planning (ACP), palliative care evaluations, and clinical outcomes during the periprocedural period were recorded. For patients who died during the study period, the use of palliative care prior to death were noted. Patients who received ACP or palliative care were compared with those who did not. The cohort consisted of 192 patients who underwent major open aortic surgery. The mean age was 63 years (SD 12.3) and the majority of patients were male (73.4%) and white (64.1%). Thirty-nine (20.6%) operations were classified as emergent. At the time of their operation, 16.7% (n=32) of patients had an ACP document on file. Of the 38 documents on file, most were durable power of attorney (DPOA) (86.8%) documents while a smaller percentage were physician orders for life-sustaining treatment (POLST) (13.2%). There were no patients with Do Not Resuscitate and/or Intubate (DNR/DNI), living will, or organ/tissue donation orders noted in their chart prior to surgery. One percent (n=2) of patients had a palliative evaluation prior to their operation. During the perioperative period, an additional 2 (1%) of patients had advanced care planning documentation and 7 (3.7%) of patients underwent palliative care evaluation. Fifteen percent of patients (n=28) died during the perioperative period and an additional 21 patients died by the end of the study period for a total mortality of 25.2% in the study population. Among patients that died during the perioperative period, 28.6% (n=8 out of 28) received palliative care. Overall, 28.6% of all study patients that died (n=14 out of 49) received a palliative care evaluation prior to or during their terminal hospitalization. Patients who had ACP documents or who received palliative care consultations prior to surgery were older (p=0.01), more likely to be on Medicare or Medicaid (p=0.004), and more likely to have a history of solid organ malignancy (p=0.03). The median interval between surgery and receiving palliative care was 20 (IQR 3-71) days. The median interval between palliative care and death was 5 (IQR 2-13) days. Patients who utilized ACP or PC were more likely to die at home (p=0.05). Despite a high mortality and morbidity rate, ACP documentation is poor for patients undergoing major open aortic surgery. Palliative care interventions tend to be performed closer to the end of life, suggesting a missed opportunity to define goals of care.

Clinical practice guideline supported administration of monoclonal antibody therapy for high-risk patients with COVID-19: Experience of a quaternary care centre

Background: Immunocompromised patients remain at risk of progression to severe COVID-19 disease. Methods: We describe clinical COVID-19-related outcomes after administration of anti-SARS-CoV-2 monoclonal antibodies (mAb) following institutional clinical practice guidelines (CPGs) in 205 high-risk patients between November 2021 and April 2022 at a Canadian quaternary care centre. Results: Median patient age was 59 years; 102 (50%) were female. Eighty-two (40%) were transplant recipients, 47 (23%) patients had hematologic malignancies, 25 (12%) had solid organ malignancies, and 51 (25%) had another indication. Forty-eight (23%) had received fewer than two doses of anti-SARS-CoV-2 vaccines. The majority (80%) had mild disease at presentation with 14% moderate and 6% severe. Median time from symptom onset to mAb administration was 3 days (IQR 2.0-5.5 days). Of those who received mAb as outpatients, 90 (93%) had favourable clinical outcomes (no COVID-19-related hospitalizations or death within 3 months). Of those who received mAb as inpatients, 93 (86%) had favourable outcomes (discharged without COVID-19-related re-admission or death), 4% were re-admitted, and 10% died. In logistic regression analysis, only disease severity at time of mAb administration was associated with unfavourable outcomes. Fewer than two vaccine doses was not associated with unfavourable outcomes, suggesting potential benefit among the under-vaccinated. There was a significant difference in adherence to CPGs between administration of mAb in outpatients versus inpatients (adherent for 85% versus 58%, p<0.001), where non-adherence occurred in cases of severe disease. Conclusion: CPG-supported mAb administration for management of COVID-19 in high-risk patients was associated with favourable clinical outcomes and may be a useful model to guide future therapies.

Artificial intelligence system for identification of overlooked lung metastasis in abdominopelvic computed tomography scans of patients with malignancy.

This study aimed to evaluate whether an artificial intelligence (AI) system can identify basal lung metastatic nodules examined using abdominopelvic computed tomography (CT) that were initially overlooked by radiologists. We retrospectively included abdominopelvic CT images with the following inclusion criteria: a) CT images from patients with solid organ malignancies between March 1 and March 31, 2019, in a single institution; and b) abdominal CT images interpreted as negative for basal lung metastases. Reference standards for diagnosis of lung metastases were confirmed by reviewing medical records and subsequent CT images. An AI system that could automatically detect lung nodules on CT images was applied retrospectively. A radiologist reviewed the AI detection results to classify them as lesions with the possibility of metastasis or clearly benign. The performance of the initial AI results and the radiologist's review of the AI results were evaluated using patient-level and lesion-level sensitivities, false-positive rates, and the number of false-positive lesions per patient. A total of 878 patients (580 men; mean age, 63 years) were included, with overlooked basal lung metastases confirmed in 13 patients (1.5%). The AI exhibited an area under the receiver operating characteristic curve value of 0.911 for the identification of overlooked basal lung metastases. Patient- and lesion-level sensitivities of the AI system ranged from 69.2% to 92.3% and 46.2% to 92.3%, respectively. After a radiologist reviewed the AI results, the sensitivity remained unchanged. The false-positive rate and number of false-positive lesions per patient ranged from 5.8% to 27.6% and 0.1% to 0.5%, respectively. Radiologist reviews significantly reduced the false-positive rate (2.4%-12.6%; all P values < 0.001) and the number of false-positive lesions detected per patient (0.03-0.20, respectively). The AI system could accurately identify basal lung metastases detected in abdominopelvic CT images that were overlooked by radiologists, suggesting its potential as a tool for radiologist interpretation. The AI system can identify missed basal lung lesions in abdominopelvic CT scans in patients with malignancy, providing feedback to radiologists, which can reduce the risk of missing basal lung metastasis.

229TiP A phase II trial of a neural network-based treatment decision support tool in patients (pts) with refractory solid organ malignancies

229TiP A phase II trial of a neural network-based treatment decision support tool in patients (pts) with refractory solid organ malignancies

UK national observational cohort study investigating Tolerance of Anti-cancer Systemic Therapy in the Elderly: the TOASTIE study

ObjectiveThe Cancer and Aging Research Group (CARG) score was developed to predict severe chemotherapy-induced toxicity risk in older adults; validation study results have varied. The Tolerance of Anti-cancer Systemic Therapy...

Efficacy of Tixagevimab/Cilgavimab as Pre-Exposure Prophylaxis against Infection from SARS-CoV-2 and Severe COVID-19 among Heavily Immunocompromised Patients: A Single-Center, Prospective, Real-World Study.

COVID-19 continues to pose a threat to immunocompromised individuals, even with vaccination. The monoclonal antibodies (mAbs) tixagevimab/cilgavimab (TXG/CIL) provide targeted prophylaxis against SARS-CoV-2 with the benefit of a prolonged half-life. Although approved for COVID-19 prevention, there is limited data on their effectiveness among heavily immunocompromised populations. We conducted a prospective, observational study at Laiko General Hospital, Athens, Greece, from August to December 2022 to investigate the efficacy of TXG/CIL as a form of pre-exposure prophylaxis in immunocompromised patients. Data on breakthrough SARS-CoV-2 infections were collected over a six-month follow-up period. Of the 375 participants (mean age 61.3 ± 14.1 years; 59.7% male), 76 (20.3%) developed breakthrough SARS-CoV-2 infections, with an incidence of 3.81 cases/100 patient months. Hospitalization was required for 21 patients (5.6%), with a median stay of 14 days. Seven deaths were recorded, with only one attributed to COVID-19. Previous infection (OR 0.46, 95% CI 0.26-0.82) and hybrid immunity (OR 0.52, 95% CI 0.29-0.92) can protect against new infection. Solid organ malignancy significantly increased the risk of severe outcomes among those infected (OR 7.4, 95% CI 2.2-24.7, p = 0.001). TXG/CIL provides effective prophylaxis against COVID-19 in immunocompromised patients. Future strategies should focus on developing new mAb combinations to address emerging SARS-CoV-2 variants and protect vulnerable populations.

Clinical management of oligometastatic cancer: Applying multidisciplinary tumor board recommendations in practice

AimsMultidisciplinary tumor boards (MDTs) are an integral part of ensuring high-quality, evidence-based and personalized cancer care. In this study, we aimed to evaluate the adherence to and implementation of MDT recommendations in patients with oligometastatic disease (OMD). MethodsWe screened all oncologic positron emission tomography (PET) scans conducted at a single comprehensive cancer center in 2020. Patients were included if they had evidence of imaging-based OMD from a solid organ malignancy on the index scans, had their OMD case discussed at an MDT, and were treated and followed up at the same center. A switch away from the MDT-recommended treatment modalities was classified as a major deviation; non-MDT-mandated adjustments to a recommended treatment modality were coded as minor deviation. Clinical data was obtained via chart review; statistical calculations were computed using the R software. ResultsAfter review of PET and/or concurrent brain scans, 787 cases of OMD were identified. Thereof, 347 (44.1 %) cases were discussed at MDT, of which 331 (42.1 %) were therapeutically managed and subsequently followed. The three most commonly recommended therapies were systemic therapy (35.6 %), multimodality treatment including definitive local therapy (17.8 %), and radiotherapy (13.9 %). A major deviation was recorded in 16.3 % of cases (most commonly: none of the MDT-recommended treatment modalities were performed: 19 (35.2 %); not all MDT-planned treatment modalities were performed: 12 (22.2 %); and additional treatment modality was performed: 11 (20.3 %). A minor deviation was found in 1.5 % of cases. On multivariable regression, number of distant metastases (n > 1) was associated with a major deviation (OR: 1.85; 95 % CI, 1.0–3.52). Major deviations were associated with a significantly worse OS (p = 0.0034). ConclusionsAdherence to and implementation of MDT recommendations in OMD patients was generally high (83.7%). Major deviations might be further reduced by more careful and elaborate discussions of OMD patient characteristics s and patient preferences.

Novel-and Not So Novel-Inhibitors of the Multifunctional CRM1 Protein.

Chromosome Region Maintenance 1 (CRM1), also known as Exportin 1 (XPO1), is a protein that is critical for transport of proteins and RNA to the cytoplasm through the nuclear pore complex. CRM1 inhibition with small molecule inhibitors is currently being studied in many cancers, including leukemias, solid organ malignancies and brain tumors. We review the structure of CRM1, its role in nuclear export, the current availability of CRM1 inhibitors, and the role of CRM1 in a number of distinct cellular processes. A deeper understanding of how CRM1 functions in nuclear export as well as other cellular processes may allow for the development of additional novel CRM1 inhibitors.

Cisplatin-induced bone marrow failure in an adult patient with Fanconi anemia.

Fanconi anemia (FA) is a genetic disorder characterized by bone marrow failure typically developing in the first decade of life, congenital abnormalities, and an increased predisposition to malignancy. However, patients with FA can remain undiagnosed until adulthood and present with solid organ malignancies. Due to impaired DNA repair mechanisms, patients with FA are highly susceptible to severe bone marrow toxicity when treated with cisplatin. A 38-year-old woman, diagnosed with locally advanced squamous cell carcinoma (SCC) of the uterine cervix, underwent treatment with weekly cisplatin concurrent with radiotherapy. After the second week of cisplatin treatment, she presented with severe pancytopenia. The prolonged and severe pancytopenia following cisplatin and radiation, along with cervical SCC in the absence of risk factors and the presence of parental consanguinity, raised the possibility of FA as the underlying cause. Whole exome sequencing revealed a homozygous FANCI c.668A > C (p.Lys223Thr) missense variant confirming the diagnosis of FA. The pancytopenia exhibited a protracted course, necessitating admission and supportive treatment with antibiotics, red blood cell and platelet transfusions, as well as filgrastim and eltrombopag. Eventually, the pancytopenia improved after approximately 40 days of hospitalization. SCC of the head and neck or gynecologic organs in a young adult without known risk factors should prompt consideration of FA. Cisplatin should be avoided in patients with FA.

Personalized treatment using predictive biomarkers in solid organ malignancies: A review.

In recent years, the influence of specific biomarkers in the diagnosis and prognosis of solid organ malignancies has been increasingly prominent. The relevance of the use of predictive biomarkers, which predict cancer response to specific forms of treatment provided, is playing a more significant role than ever before, as it affects diagnosis and initiation of treatment, monitoring for efficacy and side effects of treatment, and adjustment in treatment regimen in the long term. In the current review, we explored the use of predictive biomarkers in the treatment of solid organ malignancies, including common cancers such as colorectal cancer, breast cancer, lung cancer, prostate cancer, and cancers associated with high mortalities, such as pancreatic cancer, liver cancer, kidney cancer and cancers of the central nervous system. We additionally analyzed the goals and types of personalized treatment using predictive biomarkers, and the management of various types of solid organ malignancies using predictive biomarkers and their relative efficacies so far in the clinical settings.

Extensive Multiorgan and Neurological Involvement on F-18 FDG PET-CT in a Case of Rosai-Dorfman Disease

AbstractRosai-Dorfman disease (RDD) is a rare benign proliferative disorder. Lymph nodes are the usual and common sites of involvement. Involvement of the extranodal site is also documented in the literature. 18F-fluorodeoxyglucose positron emission tomography computed tomography (F18-FDG PET CT) is a valuable whole-body imaging modality in staging and treatment response of various lymphoproliferative and solid organ malignancy. Similarly, PET CT survey can detect the involved sites of various body systems, infective or inflammatory diseases, and provide guidance for biopsy and to reach to diagnosis. Here, we present a case of RDD, who presented with neurological manifestations and on F18-FDG PET CT, diagnosed with multiorgan involvement.

Toxicity of immune checkpoint inhibitors and tyrosine kinase inhibitor combinations in solid tumours: a systematic review and meta-analysis.

https://www.crd.york.ac.uk/prospero/, identifier CRD42022367416.

Low rates of complications and β-lactam resistance in viridans group streptococci bloodstream infection among cancer patients receiving chemotherapy.

Viridans group streptococci (VGS) bloodstream infection (BSI) frequently occurs in cancer patients receiving chemotherapy, and is associated with infective endocarditis (IE) in up to 20% of cases in the general population. In cancer patients receiving chemotherapy with VGS BSI, we aimed to: (i) determine the incidence of infective complications including IE, (ii) assess the utility of echocardiography in this patient population, (iii) determine the duration and type of antimicrobial therapy received for monomicrobial infections, and (iv) determine the evolution of antimicrobial resistance. VGS BSIs (excluding Streptococcus pneumoniae and Streptococcus pseudopneumoniae) in cancer patients receiving chemotherapy were identified from a statewide public pathology database between 2013 and 2022 at our tertiary centre. Medical records were accessed for clinical, microbiological and radiological data. Of 581 patient episodes screened, 183 episodes involving 171 patients met inclusion criteria. Of these, 51% were bone marrow transplantation (BMT) patients, 40% were non-BMT haematology patients, and 8% were solid organ malignancy patients. The median age was 55 years, and 96% were neutropenic at the time of blood culture collection. A transthoracic echocardiogram was performed for 71% of episodes, and one patient met modified Duke's criteria for definite IE, although this diagnosis was not suspected on clinical grounds. Other complications were uncommon. Benzylpenicillin resistance was rare (2.9%) and did not change over time. Most episodes (75%) were treated with piperacillin/tazobactam. For monomicrobial BSIs, the median antibiotic duration was 5 days (IQR 2-7) post-neutropenia resolution. Infective complications and antimicrobial resistance are rare in cancer patients with VGS BSI. This may provide a safe opportunity to limit both investigations (e.g. echocardiogram) and prolonged exposure to broad-spectrum antimicrobials.

Mucocutaneous Manifestations among Patients with Malignancies at a Tertiary Care Center in Maharashtra: A Cross-Sectional Study

Abstract Background: Malignant disorders are a leading cause of mortality and morbidity. Cutaneous manifestations may be presenting features of internal malignancies, leading to diagnosis of occult tumors, while others may occur as adverse reactions to therapeutic modalities. Aims and Objectives: To classify cutaneous manifestations among patients with malignant disorders, document their clinical profile, and analyze them with respect to age, gender, type of malignancy, and treatment. Materials and Methods: One hundred twenty patients with proven malignancy presenting with mucocutaneous lesions were enrolled in the cross-sectional study. On the basis of history, clinical examination, investigations and skin biopsy, the lesions were classified as (1) Primary cutaneous malignancy, (2) Cutaneous metastasis, (3) Paraneoplastic syndromes, (4) Mucocutaneous manifestations not related to malignancies, (5) Adverse effects secondary to treatment modalities. Results: One hundred twenty patients comprised 70 females (58.3%) and 50 males (41.7%). They were categorized as primary cutaneous malignancy (20.2%), hematological malignancies (15%), solid organ malignancy (50.9%), and gastrointestinal malignancies (5%). HIV seropositivity was seen in two patients (1.6%). Maximum belonged to Category 5 (60, 50%), of which 52 (86.7%) were adverse effects of chemotherapy with single patient showing radiation dermatitis and one patient in Category 3 (0.8%). Eleven patients showed cutaneous metastasis (9.1%), predominantly carcinoma breast. Clinically, primary cutaneous malignancies often presented as ulceronodular growths with squamous cell carcinoma being the most common histopathological type (30%). Anagen effluvium was the most common (35%) manifestation overall and in solid organ malignancies followed by melanonychia (16, 13.33%), cutaneous xerosis (9, 7.5%), and mucocutaneous hyperpigmentation (23, 19.16%). Conclusions: Mucocutaneous manifestations need prompt attention to facilitate timely diagnosis and improved outcomes.

Six-year evaluation of device-associated nosocomial infections in intensive care units.

Invasive device-associated nosocomial infections commonly occur in intensive care units (ICUs). These infections include intravascular catheter-related bloodstream infection (CRBSI), ventilator-associated pneumonia (VAP), and catheter-associated urinary tract infection (CAUTI). This study aimed to evaluate the factors associated with invasive device-associated nosocomial infections based on the underlying diseases of the patients and antibiotic resistance profiles of the pathogens causing the infections detected in the ICU in our hospital over a five-year period. Invasive device-associated infections (CRBSI, VAP, and CAUTI) were detected retrospectively by the laboratory- and clinic-based active surveillance system according to the criteria of the US Centers for Disease Control and Prevention (CDC) in patients hospitalized in the ICU of the tertiary hospital between 1 January 2018 and 30 June 2023. A total of 425 invasive device-associated nosocomial infections and 441 culture results were detected (179 CRBSI, 176 VAP, 70 CAUTI). Out of them, 57 (13.4%) patients had hematological malignancy, 145 (34.1%) had solid organ malignancy, and 223 (52.5%) had no histopathologic diagnosis of any malignancy. An increase in extended-spectrum beta lactamase (ESBL) and carbapenem resistance in pathogens was detected during the study period. Antibiotic resistance of the Gram-negative bacteria associated with invasive device-associated infections increased during the study period. Antimicrobial stewardship will reduce rates of nosocomial infections, reduce mortality, and shorten hospital stay. Long-term catheterization and unnecessary antibiotic use should be avoided.

SARS-CoV-2 Polymerase Chain Reaction Cycle Threshold Trends in Patients Who Are Immunocompromised and Implications for Isolation Precautions.

Among 495 patients who were immunocompromised and tested positive for SARS-CoV-2, polymerase chain reaction cycle thresholds remained <33 beyond 20 days more frequently in patients with hematologic malignancies, particularly those receiving B-cell-depleting or Bruton tyrosine kinase inhibitor therapy, as compared with those with solid organ malignancy (26% vs 5%).

Trends in phase 1 oncology clinical trials across Australia; Analysis of ClinicalTrials.gov 2012-2022.

Phase 1 oncology trials provide access to new therapies and may improve cancer outcomes. Phase 1 trials conducted in the Asian-Pacific region are increasing at a faster rate than the global trend. This study aimed to describe the changing landscape of phase 1 oncology trials in Australia in the last decade. This cross-sectional study reviewed phase 1 oncology trials registered on ClinicalTrials.gov conducted in Australia. Phase 1 trials were included for analysis if they enrolled adults with solid organ malignancies, used at least one systemic agent, and were first registered between January 1, 2012, and December 31, 2022. The number of trials, site locations, sponsor type, and drug class were analyzed using descriptive statistics. Over the 10-year period, ClinicalTrials.gov included 493 phase 1 clinical trials across 71 Australian sites. Most sites were in metropolitan locations; in Melbourne, trials were concentrated within selected sites, while in Sydney, trials were spread across a larger number of sites. The number of phase 1 trials per annum increased from 18 in 2012 to 75 in 2022. Since 2020, emerging biopharmaceutical companies have become the predominant sponsor type, a trend that is also seen globally. While most trial sponsors were North American (42%), there was increasing representation from Asian sponsors over the 10-year period (6% in 2012 to 39% in 2022). Immunomodulatory (45%) and targeted approaches (44%) accounted for most drug classes used alone or in combination. There are an increasing number of phase 1 trials conducted within Australia. Sponsors of phase 1 trials are increasingly from Asian countries and are more likely to be emerging biopharmaceutical companies.

The Incidence of Herpes Zoster Complications: A Systematic Literature Review.

The objective of this work was to summarize the incidence of herpes zoster (HZ) complications in different populations. Systematic literature review of PubMed, Embase, and Virtual Health Library records between January 1, 2002 and October 20, 2022 using search strings for HZ, complications, and frequency measurements. The review included 124 studies, most conducted in the general population (n = 93) and on individuals with comorbidities (n = 41) ≥ 18years of age. Most studies were conducted in Europe (n = 44), Asia (n = 40), and North America (n = 36). Postherpetic neuralgia (PHN) was the most studied neurological complication. Variable relative PHN incidence was found in the general population (2.6-46.7%) or based on diagnosis: immunocompromised (3.9-33.8%), depression (0-50%), and human immunodeficiency virus (HIV) (6.1-40.2%). High incidence rates were observed in hematological malignancies (HM) and solid organ malignancies (132.5 and 93.7 per 1000 person-years, respectively). Ocular complications were frequently reported with herpes zoster ophthalmicus (HZO). The relative incidence (incidence rate) of HZO in the general population was reported as 1.4-15.9% (0.31-0.35 per 1000 person-years). High relative incidence was observed in HIV (up to 10.1%) and HM (3.2-11.3%). Disseminated HZ was the most frequently reported cutaneous complication. The relative incidence of disseminated HZ was 0.3-8.2% in the general population, 0-0.5% in the immunocompetent, and 0-20.6% in patients with comorbidities. High relative incidence was reported in HM and solid organ transplant (up to 19.3% and 14.8%, respectively). Most reported complications were neurological (n = 110), ocular (n = 48), and cutaneous (n = 38). Few studies stratified complications by age or gender (or both). Incidence appeared higher in select immunocompromised populations. Higher incidence was associated with older age in several studies; the general association with gender was unclear. Variable incidence of HZ complications was reported by population subgroup. Further research is required to quantitatively analyze incidence by age, gender, and location.