Oncology clinical trial disruption during the COVID-19 pandemic: a COVID-19 and cancer outcomes study.

BACKGROUND: COVID-19 disproportionately impacted patients with cancer as a result of direct infection, and delays in diagnosis and therapy. Oncological clinical trials are resource-intensive endeavors that could be particularly susceptible to disruption by the pandemic, but few studies have evaluated the impact of the pandemic on clinical trial conduct. PATIENTS AND METHODS: This prospective, multicenter study assesses the impact of the pandemic on therapeutic clinical trials at two large academic centers in the Northeastern United States between December 2019 and June 2021. The primary objective was to assess the enrollment on, accrual to, and activation of oncology therapeutic clinical trials during the pandemic using an institution-wide cohort of (i) new patient accruals to oncological trials, (ii) a manually curated cohort of patients with cancer, and (ii) a dataset of new trial activations. RESULTS: The institution-wide cohort included 4756 new patients enrolled to clinical trials from December 2019 to June 2021. A major decrease in the numbers of new patient accruals (-46%) was seen early in the pandemic, followed by a progressive recovery and return to higher-than-normal levels (+2.6%). A similar pattern (from -23.6% to +30.4%) was observed among 467 newly activated trials from June 2019 to June 2021. A more pronounced decline in new accruals was seen among academically sponsored trials (versus industry sponsored trials) (P < 0.05). In the manually curated cohort, which included 2361 patients with cancer, non-white patients tended to be more likely taken off trial in the early pandemic period (adjusted odds ratio: 2.60; 95% confidence interval 1.00-6.63), and substantial pandemic-related deviations were recorded. CONCLUSIONS: Substantial disruptions in clinical trial activities were observed early during the pandemic, with a gradual recovery during ensuing time periods, both from an enrollment and an activation standpoint. The observed decline was more prominent among academically sponsored trials, and racial disparities were seen among people taken off trial.

COVID-19 vaccination and breakthrough infections in patients with cancer.

BACKGROUND: Vaccination is an important preventive health measure to protect against symptomatic and severe COVID-19. Impaired immunity secondary to an underlying malignancy or recent receipt of antineoplastic systemic therapies can result in less robust antibody titers following vaccination and possible risk of breakthrough infection. As clinical trials evaluating COVID-19 vaccines largely excluded patients with a history of cancer and those on active immunosuppression (including chemotherapy), limited evidence is available to inform the clinical efficacy of COVID-19 vaccination across the spectrum of patients with cancer. PATIENTS AND METHODS: We describe the clinical features of patients with cancer who developed symptomatic COVID-19 following vaccination and compare weighted outcomes with those of contemporary unvaccinated patients, after adjustment for confounders, using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19). RESULTS: Patients with cancer who develop COVID-19 following vaccination have substantial comorbidities and can present with severe and even lethal infection. Patients harboring hematologic malignancies are over-represented among vaccinated patients with cancer who develop symptomatic COVID-19. CONCLUSIONS: Vaccination against COVID-19 remains an essential strategy in protecting vulnerable populations, including patients with cancer. Patients with cancer who develop breakthrough infection despite full vaccination, however, remain at risk of severe outcomes. A multilayered public health mitigation approach that includes vaccination of close contacts, boosters, social distancing, and mask-wearing should be continued for the foreseeable future.

Association of clinical factors and recent anticancer therapy with COVID-19 severity among patients with cancer: a report from the COVID-19 and Cancer Consortium.

BACKGROUND: Patients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies. PATIENTS AND METHODS: Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anticancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients). RESULTS: A total of 4966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic black race, Hispanic ethnicity, worse Eastern Cooperative Oncology Group performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count; high absolute neutrophil count; low platelet count; abnormal creatinine; troponin; lactate dehydrogenase; and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anticancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality. CONCLUSIONS: Clinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anticancer therapies. CLINICAL TRIAL IDENTIFIER: NCT04354701.

Beyond first-line systemic treatment for metastatic urothelial carcinoma of the bladder.

Metastatic urothelial carcinoma of the bladder is a rarely curable disease. Patients receive systemic therapy with limited response rates and survival benefits. The rescue regimens of these patients who have failed first-line treatment had remained problematic until the recent advances. Several trials with novel regimens, including immune checkpoint inhibitors and targeted therapy, to salvage relapsed urothelial carcinoma of the bladder have recently been published. However, the choice of an optimal treatment regimen remains challenging in the absence of randomized trials comparing regimen sequences. Daily clinical cases provoke the question of whether there is a preferred second-line regimen. This paper provides an overview of recent trials and proposes a management algorithm based on subgroup analyses and prognostic features.

Validity and reliability of different techniques of neck-shaft angle measurement.

AIM: To determine a valid and reliable neck-shaft angle (NSA) measurement method while rotating the pelvises in increments of 5° in order to simulate patient malpositioning. MATERIALS AND METHODS: CT images of 17 patients were used to produce digitally reconstructed radiographs in frontal and lateral views and three-dimensional (3D)-reconstructions of the femurs, considered to be the reference standard. Malpositioning was simulated by axially rotating the frontal radiographs from 0° to 20°. Three operators measured in two-dimensions the NSA using four different methods, three times each, at each axial rotation (AR) position. Method 1 (femoral neck axis drawn by joining the centre of the femoral head (CFH) to the median of the femoral neck base; femoral diaphysis axis drawn by joining the median of two lines passing through the medial and lateral edges of the femoral axis below the lesser trochanter) and method 2 (femoral axis taken as the median of a triangle passing through base of femoral neck and medial and lateral head-neck junction; femoral diaphysis as previous) were described for the first time; method 3 was based on a previous study; method 4 was a free-hand technique. Reliability, validity, and global uncertainty were assessed. RESULTS: Method 1 showed the best reliability and validity. The global uncertainty also showed minimal values for method 1, ranging from 7.4° to 14.3° across AR positions. CONCLUSION: Method 1, based on locating the CFH, was the most reliable and valid method and should be considered as a standardised two-dimensional NSA measurement method for clinical application.

Normative spino-pelvic sagittal alignment of Lebanese asymptomatic adults: Comparisons with different ethnicities.

BACKGROUND: Normative values of sagittal alignment are used as references for the diagnosis and treatment of spinal pathologies. There are currently no reference values for the normative sagittal alignment of Lebanese subjects. The objective is to describe normative values of full body sagittal alignment parameters in asymptomatic Lebanese adults and to compare the sagittal alignment of this population to that of populations of various origins. METHODS: Included subjects were aged 18 to 28 years old. Each subject underwent a full body biplanar X-ray exam with measurement of spine, pelvis and lower limb parameters of sagittal alignment. The sagittal alignment of the Lebanese population was compared to that of other ethnicities, previously reported in the literature, using one-way ANOVA. RESULTS: Ninety-two asymptomatic Lebanese young adult volunteers (48 males, 44 females, age=21.5±2.2 years) were enrolled in this study. The mean curvature in the cervical spine was kyphotic (-4.3°) in women, while it was lordotic in men (5.4°). Men were found to be significantly more kyphotic than women (-58.3° vs. -53.0°; p<0.01) but both sexes were found to have similar lordosis (61.6°) and pelvic incidence (52.0°). Lebanese subjects had intermediate pelvic incidence compared to other ethnicities but showed significantly higher thoracic kyphosis (p<0.01) and lumbar lordosis (p<0.01) compared to all other ethnicities. CONCLUSIONS: This study established reference normative values for young adult Lebanese subjects. Most women were found to have kyphotic cervical spines. The sagittal alignment of Lebanese subjects differed significantly compared to that of other ethnicities. LEVEL OF EVIDENCE: Level IV - cross sectional study.

Influence of patient rotational malpositioning on pelvic parameters assessed on lateral radiographs.

AIM: To estimate the effect of patients' axial rotation (AR) during pelvic radiograph acquisition, on the reliability and validity of sagittal pelvic parameters. MATERIALS AND METHODS: Lateral digitally reconstructed radiographs (LDRRs) were obtained from the pelvic computed tomography (CT) scans of eight children and nine adults. Then, the AR of the pelvis was simulated and the corresponding LDRRs were reconstructed at 5°, 10°, 15°, and 20° of the AR. Pelvic parameters were measured digitally on each radiograph. Intra- and interobserver variability were evaluated at each AR position (three operators repeated the measurements three times each). The bias on each clinical parameter, in each AR position, was calculated relatively to the 0° position. RESULTS: Interobserver variability increased similarly in children and adults with AR. It reached 4.4° for pelvic incidence and 4.7° for the sacral slope at 20° of AR. Biases on radiological parameters increased with AR and exceeded the acceptable threshold of errors when AR reached 10°. A linear regression was established (R2=0.834, p<0.0001) in order to estimate the AR of a patient on a lateral pelvic radiograph based on the measurement of the bifemoral distance normalized to the sagittal pelvic thickness. CONCLUSIONS: AR of patients during radiograph acquisition can be estimated in clinical practice, which would allow physicians to discard any radiographs where the calculated AR exceeded 10°.

A podoscopic and descriptive study of foot deformities in patients with Down syndrome.

INTRODUCTION: Subjects with Down syndrome (DS) are known to be affected by various foot deformities. Despite the fact that some of these deformities have been reported in the literature, a more comprehensive description would be of benefit. The aim of this study is to investigate the prevalence of known foot deformities in patients with DS and of other previously non-described foot anomalies in this population. HYPOTHESIS: Subjects with DS have an increased prevalence of foot deformities compared to control subjects. METHODS: Fifty-five subjects with DS (age: 14.6±7.4 years) had undergone podiatric clinical and podoscopic examinations to study their main foot deformities and their footprints, respectively. The results of these examinations were compared to those of an age-matched asymptomatic control group of fifty-three subjects (age: 13.4±11.2 years). RESULTS: Significantly more prevalent foot deformities were found in the DS group: hallux valgus (36.4%), syndactyly between the 2nd and 3rd toes (9.1%), grade II pes planus (39.1%) and grade III pes planus (30%). Moreover, joint laxity (43.6%) was significantly more prevalent in the DS group. Furthermore, the presence of an increased space between the 1st and 2nd toes in patients with DS and its prevalence (73.6%) were described for the first time. A multivariate analysis revealed a significant relationship between the presence of joint laxity and flatfoot in only the control but not the DS group. Other foot deformities were found to be consistently more frequent in the DS population but not significantly higher than the control group. DISCUSSION: Although subjects with DS had significantly greater joint laxity and BMI compared to the control group, neither of these factors was found to be related to the increased prevalence of flatfoot in DS patients. LEVEL OF EVIDENCE: IV-retrospective study.