BACKGROUND: COVID-19 outbreak rapidly spread since early 2020 leading to the implementation of nationwide lockdowns. To cope with this sudden change, management guidelines were quickly published to adapt oncological care, with potential impact on cancer outcomes.
METHODS: We conducted a retrospective comparative cohort study to assess the impact of the COVID-19 outbreak in 2020 on cancer outcomes in metastatic patients. Two cohorts of metastatic patients receiving intravenous (iv) therapy in a French oncological day care hospital were assessed: a 2020 cohort during the first French lockdown, and a 2018 historical cohort before the COVID-19 pandemic. We performed a propensity score analysis to match patients from the two cohorts. After one-year follow-up, we compared progression-free survival (PFS) and overall survival (OS) between cohorts. Adaptations of medical oncological treatments in 2020 were also analysed.
RESULTS: The 376 patients of the 2020 cohort were matched with 376 of the 2018 cohort. No SARS-CoV-2 infection was observed in the 2020 cohort. The adjusted PFS was significantly shorter in 2020 compared to 2018 (HR = 1.23; 95% CI: 1.03-1.46), as well as among patients without treatment adaptation compared to matched patients of the 2018 cohort (HR = 1.33; 95% CI: 1.10-1.61). We did not observe any significant difference of PFS among the group with treatment adaptations. OS was not significantly different.
CONCLUSIONS: Metastatic cancer patients treated during the first lockdown had a higher risk of disease progression 1 year after COVID-19 outbreak. However, oncological treatment adaptations or SARS-CoV-2 infections do not explain these results. A longer follow-up is needed to observe the impact on OS.

There are limited real-world data on the effectiveness of strategies used to manage adverse events (AEs) in patients with advanced renal cell carcinoma (RCC) treated with axitinib. This retrospective chart review examined the AE profile and effect of axitinib modifications on AE resolution/improvement and treatment discontinuation.
A retrospective physician-administered chart review was conducted. Adult patients with advanced RCC treated with first-line axitinib plus checkpoint inhibitor (CPI) therapy (ie, avelumab or pembrolizumab) and who had documented frequently reported axitinib-related AEs of fatigue, diarrhea, nausea, hypertension, or palmar-plantar erythrodysesthesia were included. Physician characteristics, patient characteristics, AE characteristics, AE management strategies used, AE resolution/improvement, and treatment duration were described. The effect of strategies used to manage AEs (axitinib dose reduction or treatment interruption) on AE resolution/improvement was evaluated by logistic regression.
Among 219 patients (median age: 62 years, 65% male), 70 (32%) were treated with axitinib + avelumab and 149 (68%) received axitinib + pembrolizumab. Axitinib modifications increased the likelihood of AE resolution/improvement compared with no modifications (adjusted odds ratio: 6.34, P < .001). In the subset of patients who discontinued treatment among those with or without axitinib modifications, mean treatment duration was 7.0 and 1.7 months, respectively.
Toxicities experienced by patients with advanced RCC treated with first-line axitinib-CPI in the real world can be effectively managed by axitinib modifications, thereby prolonging treatment duration. (Clinicaltrials.gov identifier: NCT04682587).

A 59-year-old man with relapsed pulmonary TB developed rifampin resistance. He presented with chronic untreated hepatitis B, which developed into liver cirrhosis, type 2 diabetes with diabetic retinopathy, and osteoarthritis of right knee. His initial MDR regimen included levofloxacin, cycloserine, bedaquiline, linezolid, and high-dose isoniazid. He developed episodes of linezolid-induced myelosuppression, resulting in temporary discontinuation and dose reduction, and ultimately, substitution of linezolid. On the seventh month of treatment, he developed severe depression with visual hallucination, resulting in cycloserine dose reduction. We maintained the principle of at least 4 active drugs throughout his treatment. He was considered cured after 26 months of treatment.

Following evidence from randomized controlled trials, patients with bronchiectasis unrelated to cystic fibrosis receive long-term azithromycin to reduce acute respiratory exacerbations. However, the period when azithromycin is effective and which patients are likely to most benefit remain unknown.
(i) What is the period after its commencement when azithromycin is most effective? and (ii) Which factors may modify azithromycin effects?
A secondary analysis was conducted of our previous randomized controlled trial involving 89 indigenous children with bronchiectasis unrelated to cystic fibrosis. Semi-parametric Poisson regression identified the azithromycin efficacy period. Multivariable Poisson regression identified factors that modify azithromycin effect.
Azithromycin was associated with fewer exacerbations per child-week during weeks 4 through 96, with the most effective period observed between weeks 17 and 62. Eleven factors were associated with different azithromycin effects; four were significant at the P < .05 level. Compared with their counterparts, higher reduction in exacerbations was observed in children with nasopharyngeal carriage of bacterial pathogens (incidence rate ratio [IRR] = 0.81 [95% CI, 0.57-1.14] vs 0.29 [0.20-0.44]; P < .001); New Zealand children (IRR = 0.73 [0.51-1.03] vs 0.39 [0.28-0.55]; P = .012); and those with higher weight-for-height z scores (interaction IRR = 0.82 [0.67-0.99]; P = .044). Compared with their counterparts, lower reduction was observed in those born preterm (IRR = 0.41 [0.30-0.55] vs 0.74 [0.49-1.10]; P = .012).
Regular azithromycin is best used for at least 17 weeks and up to 62 weeks, as these periods provide maximum benefit for indigenous children with bronchiectasis unrelated to cystic fibrosis. Several factors modified azithromycin benefits; however, these traits need confirmation in larger studies before being adopted into clinical practice.
Australian New Zealand Clinical Trials Registry; ACTRN12610000383066.

Suicide is among the leading causes of death for adults with schizophrenia spectrum disorders. Given a paucity of evidence-based interventions tailored for psychosis, we sought to modify a promising Cognitive-Behavioral Suicide Prevention for psychosis (CBSPp) treatment for adults in US community mental health (CMH) settings using community-based participatory research methods. This article presents our modification methodology, stakeholder data and scholarly expert input, and CBSPp adaptations prior to future intervention testing. Stakeholder data (n = 25) were collected from clients, providers, and peer advocates in a CMH setting in Michigan. Findings were subsequently presented to a panel of scholarly experts in the fields of suicide and psychosis research, intervention research, and implementation science for input. Emerging themes from stakeholders include logistic, perceptual, and clinical challenges in the process of introducing this treatment in a CMH setting. Consistent with literature, buy-in and support for the delivery of a new treatment emerged as important factors in modifying and implementing CBSPp. A final modification list is presented in this paper and collaborations among stakeholders, researchers, and scholarly experts are essential to navigate psychosocial treatment innovation barriers with an overall goal of improving access, feasibility, and quality of this suicide prevention treatment.

Guidelines do not recommend FDG-PET CT for the staging of MIBC as a standard. The objectives of the study are to assess the accuracy of the FDG-PET CT for LN staging and to determine the rate of treatment modification according to FDG-PET CT results in MIBC.
From January 2005 to December 2017, we carried out a retrospective analysis of patients with MIBC who had a FDG-PET CT for staging in two expert centres in Bordeaux, France, and analyzed its clinical value in this setting. Nodal and metastatic staging on CT scan (CT) and FDG-PET CT were done independently.
Accuracy of LN staging from CT and FDG-PET CT at initial diagnosis was analyzed in 85 patients (including 70 patients treated with neoadjuvant chemotherapy (NAC)) and compared to pathological examination of resected LN. Sensitivity of FDG-PET CT was better than CT (80.8% versus 26.9%) but the specificity was low (54.2% vs. 83.1%). The Youden index was better for FDG-PET CT (0.35; 0.1 for CT) and FDG-PET CT appeared to be more accurate for determining LN staging of MIBC. FDG-PET CT findings enabled a treatment decision modification in 34/130 patients (26.1%): a therapeutic intensification (9.2%), including surgery not previously planned and/or modified fields of radiotherapy; or a de-escalation (16.9%), mostly avoiding surgery.
FDG-PET CT was more sensitive for detection of LN involvement at initial diagnosis of MIBC than CT alone. In our study, treatment decisions were modified, according to FDG-PET CT results, in almost a quarter of patients.

Changes in HIV treatment guidelines over the last two decades reflect the evolving challenges in this field. Our study examined treatment change patterns throughout a 7-year period in a large Italian cohort of HIV patients as well as the reasons and direction of changes. Treatment-naïve and -experienced HIV patients managed by Cotugno Hospital of Naples between 2014 and 2020 were analyzed. During the period, the proportion of single-tablet regimen treatment sharply increased for the naïve and experienced patients. Regimens containing integrase strand transfer inhibitors rapidly replaced those containing protease inhibitor and non-nucleoside reverse transcriptase inhibitors. The use of the tenofovir alafenamide fumarate/emtricitabine backbone increased rapidly after its introduction in the Italian pharmaceutical market, making up 63.7 and 54.9% of all treatments in naïve and experienced patients, respectively, in 2020. The main reason for treatment changes was optimization and/or simplification (90.6% in 2018; 85.3% in 2019; 95.5 in 2020) followed by adverse effects and virological failure. Our real-world analysis revealed that the majority of treatment-naïve and treatment-experienced patients received antiretroviral drugs listed as preferred/recommended in current recommendations. Regimen optimization and/or simplification is a leading cause of treatment modification, while virologic failure or adverse effects are less likely reasons for modification in the current treatment landscape.

Since the beginning of the COVID-19 pandemic, multiple changes to the provision of cancer care has been introduced to maximize patient safety and protect staff. We aimed to identify factors influencing clinicians\' decision on treatment modification during the initial phase of the pandemic, and to assess its impact on outcomes in patients with colorectal cancer.
Electronic records of patients seen in a large United Kingdom tertiary cancer center was reviewed. The frequency and type of changes to systemic anticancer therapy , as well as the factors predicting clinicians\' decision were assessed.
A total of 418 patients; mean age 63 ± 12 years and 57% male were included. More than half of the patients had modification to their treatment; with treatment delay (21%) or cancellation (10%), being the most common. Majority of patients on neoadjuvant treatment (97%) proceeded with treatment, with some form of treatment modification in 20%. Half of patients on adjuvant treatment had their treatment plan modified. Overall, a change in treatment was more likely in older patients (OR 1.028 [95% CI 1.010-1.047]; P = .002), and in patients who had already received higher number of cycles of systemic anticancer therapy (OR 1.040 [95% CI 1.016-1.065]; P = .001). A change in treatment was less likely further out of the first national lockdown (OR 0.837 [95% CI 0.758-0.925]; P < .001). Patients on third-line treatment were most likely to have alterations to their treatment plan (69%, n=33/48).
During the first wave of COVID-19 in the United Kingdom, clinicians adapted clinical practice in accordance to local and national guidance, especially amongst older patients and those on third-line treatment. Further real-world data are needed to document the important impact of changes to treatment on outcomes in patients with cancer.

To investigate humoral responses and safety of mRNA SARS-CoV-2 vaccines in systemic autoimmune and autoinflammatory rheumatic disease (SAARD) patients subjected or not to treatment modifications during vaccination.
A nationwide, multicenter study, including 605 SAARD patients and 116 controls, prospectively evaluated serum anti-SARS-CoV-2 S1-protein IgG antibody titers, side-effects, and disease activity, one month after complete vaccination, in terms of distinct treatment modification strategies (none, partial and extended modifications). Independent risk factors associated with hampered humoral responses were identified by data-driven multivariable logistic regression analysis.
Patients with extended treatment modifications responded to vaccines similarly to controls as well as SAARD patients without immunosuppressive therapy (97.56% vs 100%, p = 0.2468 and 97.56% vs 97.46%, p > 0.9999, respectively). In contrast, patients with partial or without therapeutic modifications responded in 87.50% and 84.50%, respectively. Furthermore, SAARD patients with extended treatment modifications developed higher anti-SARS-CoV-2 antibody levels compared to those without or with partial modifications (median:7.90 vs 7.06 vs 7.1, p = 0.0003 and p = 0.0195, respectively). Mycophenolate mofetil (MMF), rituximab (RTX) and methotrexate (MTX) negatively affected anti-SARS-CoV-2 humoral responses. In 10.5% of vaccinated patients, mild clinical deterioration was noted; however, no differences in the incidence of deterioration were observed among the distinct treatment modification SAARD subgroups. Side-effects were generally comparable between SAARD patients and controls.
In SAARD patients, mRNA SARS-CoV-2 vaccines are effective and safe, both in terms of side-effects and disease flares. Treatment with MMF, RTX and/or MTX compromises anti-SARS-CoV-2 antibody responses, which are restored upon extended treatment modifications without affecting disease activity.

BACKGROUND: Management of patients with cancer in the current era of the COVID-19 pandemic poses a significant challenge to health care systems. Breast cancer is the most common cancer internationally. Breast cancer is a disease that involves surgery, chemotherapy, hormonal therapy, targeted therapy, radiotherapy, and, more recently, immunotherapy in its management plan. The immune system requires months to recover from these medications, and this condition is even worse in patients with metastatic breast cancer who need ongoing treatment with these drugs. Some of these drugs, such as inhibitors of cyclin-dependent kinases 4 and 6, can cause rare but life-threating lung inflammation. Patients with breast cancer who have metastatic disease to the lungs can experience deterioration of disease symptoms with COVID-19 infection. Oncologists treating patients with breast cancer are facing a difficult situation regarding treatment choice. The impact that COVID-19 has had on breast cancer care is unknown, including how to provide the best care possible without compromising patient and community safety.
OBJECTIVE: The aim of this study was to explore the views of oncologists regarding the management of patients with breast cancer during the COVID-19 pandemic.
METHODS: A web-based SurveyMonkey questionnaire was submitted to licensed oncologists involved in breast cancer management in Saudi Arabia, Egypt, and United Arab Emirates. The survey focused on characteristics of the participants, infection risk among patients with cancer, and possible treatment modifications related to different types of breast cancer.
RESULTS: The survey was completed by 82 participants. For early hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, 61 of the 82 participants (74%) supported using neoadjuvant hormonal therapy in selected patients, and 58% (48/82) preferred giving 6 over 8 cycles of adjuvant chemotherapy when indicated. Only 43% (35/82) preferred inhibitors of cyclin-dependent kinases 4 and 6 with hormonal therapy as the first-line treatment in all patients with metastatic HR-positive disease. A total of 55 of the 82 participants (67%) supported using adjuvant trastuzumab for 6 instead of 12 months in selected patients with HER2-positive breast cancer. For metastatic HER2-positive, HR-positive breast cancer, 80% of participants (66/82) supported the use of hormonal therapy with dual anti-HER2 blockade in selected patients. The preferred choice of first-line treatment in metastatic triple negative patients with BRCA mutation and programmed cell death 1 ligand 1 (PD-L1) <1% was poly(adenosine diphosphate-ribose) polymerase inhibitor according to 41% (34/82) of the participants, and atezolizumab with nab-paclitaxel was preferred for PD-L1 >1% according to 71% (58/82) of the participants.
CONCLUSIONS: Several modifications in breast cancer management were supported by the survey participants. These modifications need to be discussed on a local basis, taking into account the local infrastructure and available resources.