Certolizumab

Certolizumab is a Fab fragment of a humanized monoclonal antibody against tumor necrosis factor-alpha (TNF-alpha). Differing from the other TNF-alpha inhibitors due to the absence of Fc fragment and pegylation, it binds to both the soluble and transmembrane forms of TNF-alpha, creating a strong TNF-alpha blockage. Previously approved for psoriatic arthritis, certolizumab received another approval from FDA in 2018 for the treatment of moderate to severe chronic plaque psoriasis that does not respond to conventional systemic treatments or for which these treatments are contraindicated. Administered via subcutaneous injections, certolizumab also has a low-dose option for patients weighing less than 90 kg. Certolizumab is considered a safe biological drug that can be preferred during pregnancy and lactation.Copyright © 2022 by Turkish Society of Dermatology and Venereology.

Ablation for hepatocellular carcinoma (HCC)

Ablation includes ethanol injection, radiofrequency ablation (RFA), microwave ablation (MWA), etc. Ablation can be potentially curative, minimally invasive and easily repeatable for recurrence. RFA has been the most widely used ablation technique for liver tumors. The new-generation MWA system incorporating antenna cooling and high-power generation has attracted attention. It can create a more predictable ablation zone and a larger ablation volume in a shorter procedure time. Many high-volume centers have introduced new-generation MWA in Japan. However, many studies failed to show that new-generation MWA is superior to RFA in terms of local control and overall survival. In MWA, clinical data have been insufficient compared with those of RFA. There has been keen competition between surgical resection and ablation for almost 40 years since the era of ethanol injection. In 2021, SURF trial revealed that overall survival and recurrence-free survival were not significantly different between surgical resection and RFA. SURF trial was a multicenter randomized controlled trial in which 49 major centers in Japan enrolled patients with good hepatic function (Child-Pugh scores <= 7) and primary HCC of largest diameter <= 3 cm, and <= 3 nodules during the 6-year period of 2009-2015. The registered patients were followed for at least 5 years. As the result of SURF trial and other comparative studies, the revised Japanese clinical practice guidelines in 2021 treats hepatic resection and ablation equally for patients with <= 3 lesions, <= 3 cm in diameter. Recently, the combination of systemic and locoregional therapies has been attracting much attention. Systemic therapy using molecular targeted agents or immune checkpoint inhibitors is used for advanced HCC which cannot be treated by surgery or ablation. On the other hand, some locoregional therapies, such as hepatectomy and ablation, are potentially curative, but they cannot be indicated for advanced HCC. Combination of both therapies is an approach to improve the prognosis of advanced HCC, which is not indicated for curative treatment. Systemic therapy is used to shrink the tumor, and then locoregional therapies are performed to eradicate it. The combination may build a new strategy for advanced HCC. Ablation is highly operator-dependent. The skills and outcomes are very different from operator to operator. Before the pandemic of COVID-19, we held domestic and international training programs for intermediate and advanced doctors and hands-on seminars for young doctors. These were activities to exchange knowledge and experience and standardize the procedure. During the pandemic, we cannot get together. Since August 2020, we have conducted Japan Ablation Webinar 8 times with a total of 1,566 participants. We have also conducted International Ablation Webinar 4 times with a total of 1,272 participated doctors. Education is important to acquire skills and knowledge for successful ablation. We have established Japan Academy of Tumor Ablation (JATA) this year. There are two triggers. One is that SURF trial revealed that there is no difference between hepatectomy and ablation. The other is that ablation for lung, bone and soft tissue and kidney cancers has become reimbursed with health insurance since this September.

Radiium systemic radiotherapy - 223 patients with mCRPC. Experience of the Republic of Bashkortostan

Introduction & Objectives: The incidence of prostate cancer, both in the world and in the Russian Federation, tends to increase. In the Republic of Bashkortostan in 2021, 699 patients with this diagnosis were registered. 19.6% of patients had stage IV disease at the time of diagnosis. 5818 patients were registered, of which 361 died within a year. The effectiveness of hormonal treatment of common prostate cancer has time limitations, after which there is a development of resistance to castration and progression of the disease. To date, drugs such as kabazitaxel, sipuleucel-T vaccine, abiraterone, enzalutamide and radium-223 have been approved for use in metastatic CRPC. The purpose of the work: analysis of the experience of systemic radiotherapyand Radium - 223 patients with mCRPC in the Republic of Bashkortostan in 2021. Material(s) and Method(s): Analysis of patients who received systemic radiotherapy Radium - 223 in the Republic of Bashkortostan according to medical documentation and research data. In 2021, Radiy-223 radiotherapy was performed on 7 patients diagnosed with mCRPC. Median age 63.14 years. All patients met the criteria for treatment, i.e. had castration-resistant prostate cancer with bone metastases, without visceral metastases. All patients had concomitant pathology from the cardiovascular system, respiratory tract, endocrine system. According to the previous surgical treatment, patients were distributed as follows: orchidectomy - 4, prostatectomy - 1 and 2 patients underwent tumor biopsy. By morphology: Glisson 6 - 2 patients, Glisson 7 - 1, Glisson 8 - 3, Glisson 10 - 1. 4 patients were referred to Xofigo for radiologically confirmed progression, 3 patients were progressingin height at PSA levels. Result(s): 1 patient previously received 1 line of systemic therapy, 5 patients received 2 lines, 1 patient received 3 lines of therapy. 6 patients received all 6 courses of radiotherapy, 1 patient did not complete treatment due to COVID 19. He is expected to complete therapy. All patients are currently alive with no signs of disease progression. Serious side effects were not registered. Conclusion(s): The "therapeutic window" for the prescription of radium-223 is the period before the appearance of visceral metastases and decline of the somatic status. To achieve the maximum benefit from the appointment of radium-223, it is necessary to conduct >=5 cycles of therapy, which is possible in 1-2 treatment lines. It is necessary to select patients carefully for radiotherapy - Radium 223.Copyright © 2022 European Association of Urology. Published by Elsevier B.V.

Pulmonary parenchymal involvement secondary to subcutaneous injection of silicone gels: a case report.

Pulmonary parenchymal involvement secondary to the subcutaneous injection of silicone gels is an unusual condition which occurs more frequently in women aged between 22 and 55 years. Although different theories have been put forward about its etiology, it is unknown and the condition may cause local and systemic complications and even have a fatal outcome. Few cases have been reported in South America and there is no report of this unique entity in Peru. We present the case of a previously healthy 28-year-old male transgender patient who, after an illegal subcutaneous injection of silicone gels in the gluteal region given by a non-healthcare professional, showed progressive respiratory distress and stabbing chest pain of approximately 7 out of 10 on the pain scale within the first 24 hours. Upon admission to the emergency room, respiratory failure was objectively evidenced since the patient had an oxygen saturation of 72 % at a FiO2 of 21 %, as well as pulmonary parenchymal involvement both in the CT scan and chest X-ray with signs highly suggestive of this pathology. Using a SARS-CoV-2 RNA real-time RT-PCR test performed on a respiratory specimen, COVID pneumonia, immunodeficiency disorders and pulmonary embolism were ruled out. Since there is no standard treatment, the patient was given relevant support measures such as the administration of supplemental oxygen at a low flow rate by binasal cannula, intravenous systemic corticosteroids and antibiotic therapy, thus achieving good progress with resolution of the initial clinical presentation. Then, after 10 days of intrahospital treatment, the patient was discharged.Copyright © La revista. Publicado por la Universidad de San Martin de Porres, Peru.

The effectiveness of blended versus regular Forensic Outpatient Systemic Therapy in the treatment of juvenile antisocial behavior: a study protocol of a randomized controlled trial.

BACKGROUND: Antisocial behavior during adolescence can have long-lasting negative effects and leads to high societal costs. Forensic Outpatient Systemic Therapy (Forensische Ambulante Systeem Therapie; FAST) is a promising treatment for juveniles aged 12-21 showing severe antisocial behavior. The intensity, content and duration of FAST can be adjusted to the needs of the juvenile and their caregiver(s), which is considered crucial for effective treatment. Next to the regular version of FAST (FASTr), a blended version (FASTb) in which face-to-face contacts are replaced by minimally 50% online contacts over the duration of intervention was developed during the Covid-19 pandemic. The current study will investigate whether FASTb is equally effective as FASTr, and through which mechanisms of change, for whom, and under which conditions FASTr and FASTb work. METHODS: A randomized controlled trial (RCT) will be carried out. Participants (N = 200) will be randomly assigned to FASTb (n = 100) or FASTr (n = 100). Data collection will consist of self-report questionnaires and case file analysis, and include a pre-test at the start of the intervention, a post-test immediately after the intervention, and a six month follow-up. Mechanisms of change will be investigated using monthly questionnaires of key variables during treatment. Official recidivism data will be collected at two-year follow-up. DISCUSSION: This study aims to improve the effectiveness and quality of forensic mental health care for juveniles with antisocial behavior by studying the effectiveness of blended care, which has not been studied before in treatment of externalizing behavior. If found to be at least as effective as face-to-face treatment, blended treatment can help meet the urgent need for more flexible and efficient interventions in this field. In addition, the proposed study aims to unravel what works for whom, knowledge urgently needed in mental health care for juveniles with severe antisocial behavior. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov on 07/11/2022, registration number NCT05606978.

Maskne: Its relationship to skin microbiome and response to treatment

Mask-wearing during the ongoing COVID-19 pandemic has been associated with an increased occurrence of a form of acne mechanica, popularly termed 'maskne. However, our understanding of this entity is limited. Hence we aimed to study the role of changes in the skin microbiome in mask induced acne and its response to standard acne treatment regimens. This was a prospective observational study. Adult patients having new-onset of lesions suggestive of acne within 6 weeks of regularly wearing mask or exacerbation of pre-existing acne were recruited. Disease severity was assessed using the 'Global Acne Severity Grading System (GAGS). Sample collection was done from pustules or comedones. Treatment was given according to American Academy of Dermatology Guidelines and follow up was done till 12 weeks. Data was entered and analyzed using Statistical Package for Social Sciences (SPSS) v.25. Total 50 patients were recruited in the study. 56% patients were female and 44% were male. 60% patients had a history of similar lesions in the past. 56% patients used surgical mask, 34 % used N-95 mask and 18 % used cloth mask. The average duration of use for mask per day was 6.78 +/- 2.65. Cheeks were the most commonly involved site and 62% of patients had mild GAGS. The severity of acne was significantly higher in patients using N-95 mask ( p<0.05) but not associated with duration of mask use, history of mask re-use and use of moisturizers. 70% cases did not require systemic treatment. KOH was negative in all cases. Gram stain showed gram positive cocci and rods in 22% and 14 % cases respectively. Aerobic culture showed Staphylococcus aureus growth in 30% cases and Anaerobic culture showed Cutibacterum acnes growth in 20% cases. In our study we found that maskne presented with a milder variant of acne which in majority of cases responded well to topical treatment standardized for acne vulgaris and had a microbiome profile similar to acne vulgaris.Copyright © 2023

A rare case of CSU+CIndU resistant to systemic treatment with GCS and methotrexate initiated to Takayasu's disease

Case report Background: It is well known that chronic spontaneous urticaria (CSU) has an autoimmune etiology in 40% of cases. It is often comorbid with other autoimmune diseases and a wide spectrum of autoantibodies involved in the pathogenesis of CSU is discussed. Objective(s): We share a clinical case of a rare underline autoimmune disease with later onset of CSU and chronic induced urticaria (CIU). Case: A 38-year- old woman was admitted to the hospital with SARS-CoV- 2 infection. At the age of 22, she was diagnosed with Takayasu's disease involving the aorta, the common and external carotid artery, and the left subclavian artery. Surgical interventions were performed twice -angioplasty of the involved vessels, but in both cases restenosis of the affected arteries was observed. Regarding the underlying disease, the patient received 10 mg of methotrexate once a week and 20 mg of prednisone daily. Due to detailed history collection, the patient noted that for the last 4 months she has rashes, bright red in color, rising above the surface of the skin and accompanied by a strong burning and itching dominantly on the upper and lower extremities, trunk. Appearing every day spontaneously, they have a rounded shape (diameter of up to 40-50 mm). While liner scratching the rash has similar contour. Rash elements disappear within a few hours, do not leave traces. During the current hospitalization, a wheal element up to 40 mm in diameter was observed at the wrist area, stayed for a few hours. UAS-7 -42. According to examination: eosinophils 1000 cells/mcl (patient noticed that eosinophilia of the blood has happened before, an examination was conducted, helminthiasis and parasitosis were excluded), total IgE -more than 2000 IU/ml, antibodies to b2-glycoprotein were revealed. Freak test -negative, but the linear wheals were confirmed by retrospective photos. Result(s): In this clinical case, CSU occurs in combination with induced dermographic urticaria. This patient has extremely aggressive urticaria according to its frequency of occurrence despite therapy with systemic GCS and methotrexate. After recovery from coronavirus infection, further examination and consideration of the appointment of biologicals(anti-IgE) is planned.

Patterns of Progression and Treatment Discontinuation in a Real Life Latin American Prospective Cohort Study of Intermediate-Advanced Hepatocellular Carcinoma: Second Interim Analysis

Introduction and Objectives: Previously published regional real-world results of overall survival (OS) in Barcelona Clinic Liver Cancer (BCLC) B and C patients demanded a prospective cohort study nested in a systematic and continuous medical educational networking group. This study aimed to describe and evaluate the treatment decisions in patients with hepatocellular carcinoma (HCC) within BCLC B and C stages. Material(s) and Method(s): A multicenter prospective cohort study, conducted in different Latin American centers from Argentina, Brazil and Colombia, started on 15th May 2018 (delayed recruitment during COVID locked-down period). Patients within BCLC B or C stages were included. Survival, tumor progression and patterns of treatment suspension were evaluated. Result(s): At this second interim analysis (projected final analysis March 2023), 390 HCC BCLC-B or C patients were included (n=15 excluded);mean age 65 years, 75.6% males and 89.5% cirrhotic. Median OS since HCC diagnosis was 27.2 months. Among BCLC-B patients, the most frequent therapy was transarterial chemoembolization (TACE, 42.3%);51.8% using drug-eluting beads and 47.4% conventional TACE;with a median OS since 1st TACE of 41.9 months. Similar radiological responses after 1st TACE were observed between both modalities. Overall, 48.2% of the cohort received systemic therapy for HCC (n=188), 23.7% still on BCLC-B stage. The most frequent systemic treatments were Sorafenib (74.5%), atezolizumab bevacizumab (17.5%), and lenvatinib (12.2%), with a median OS since systemic therapy of 15.7 months. Lenvatinib or atezolizumab bevacizumab was used as the second line following sorafenib in 5 and 3 patients, respectively. The most common causes of systemic treatment discontinuation were tumor progression and liver function deterioration (15% to 36.4%). Patterns of tumor progression were not specifically associated with prognosis or treatment discontinuation. Conclusion(s): Liver function deterioration occurs in a third of patients following systemic therapies. The complexity of treatment decisions underly the need for a multidisciplinary team and the role of hepatologists.Copyright © 2023

Current Knowledge on Psoriasis During the Covid-19 Pandemic

Psoriasis is a chronic inflammatory disease associated with a de-fective epidermal barrier, in which the immune system is already activated in lesional sites of the skin, and it is thus possible that affected individuals can have different immunologic rates of viral response. This is especially impor-tant in the era of the novel coronavirus disease (COVID-19) that is affecting the entire world. Patients with psoriasis are often receiving systemic therapy which includes immunosuppressive and biologic therapy, so this new infec-tious disease has raised concerns among dermatologists regarding psoriasis treatment. Some of the risk factors of psoriasis are obesity, diabetes mellitus, and hypertension - all of which are diseases linked with negative outcomes and higher severity of COVID-19. Psoriasis is mediated by inflammatory cells and proinflammatory cytokines such as IL-17, IL-23, IFN-gamma, and TNF-alpha, and patients with skin diseases have been shown to be more susceptible to CO-VID-19 infection, but with a less severe disease course. As an anti-inflamma-tory agent, vitamin D could play a significant role in the future as a possible treatment for reducing the risk and severity of psoriasis and COVID-19. It has been suggested that patients treated with biologic therapy should continue treatment, as it has not been shown to cause severe complications of the CO-VID-19 disease. Preventive measures, including vaccination, should be taken to minimize the risk of infection and severity of the clinical outcome.Copyright © 2022, Croatian Dermatovenerological Society. All rights reserved.

Support for patients with MBC

Over the last decade we have witnessed rapid advances in the treatment of patients with metastatic breast cancer (MBC) with seminal discoveries in cancer biology, correlative biomarkers and clinical trials leading to multiple new drug approvals. While these milestones have improved survival, the science of survivorship in this population is just beginning. The diagnosis of MBC is life-changing and requires individualized and multidisciplinary support. The NCI defined the areas of epidemiology and surveillance, symptom management, psychosocial research, health-care delivery, and health behaviors as necessary fields to advance the state of the science in advanced cancer survivors. A multifaceted program addressing these domains is needed to assess MBC patients and their unique and ever-changing needs. With input from patients and providers, program components should include: therapeutic clinical trials, multidisciplinary specialty care, individualized patient navigation, peer support, continuing education, and patient reported outcome (PRO) collection to support patients living with MBC. Input for a program for MBC patients can be guided by a multidisciplinary steering committee in which patient advocates are a major voice. Patients can provide insight into what works for them, and what they are facing may be very different from the experience of an early-stage breast cancer patient. Clinical trials designed to advance the current scientific knowledge of breast cancer treatment are essential to patients living longer, more fulfilled lives with MBC. Clinical trials may include systemic therapy, local therapies such as surgery and radiation for MBC patients, side-effect management and quality of life (may put elsewhere). A comprehensive systemic therapy portfolio should include all biological subtypes as well as recommended treatment options (hormonal therapy, targeted therapy, chemotherapy, and immunotherapy). Multidisciplinary care is necessary to diagnose and treat any condition the MBC patient may encounter and is essential in providing quality care. Comorbidities and debilitating side effects arising from cancer treatment are known to be associated with inferior outcomes. MBC patients may experience lack of familiarity of some providers with novel MBC cancer treatment, side effects, and interactions of their cancer treatment with non-cancer conditions and treatment. With the increasing life expectancy of MBC patients, it is important to manage the medical comorbidities in coordination with the MBC patient's cancer treatment. Integrative Medicine helps support the quality of life of patients through providing clinical modalities such as stress management, yoga, meditation, acupuncture, massage and lifestyle counseling. Supportive care helps support cancer related fatigue and sleep challanges, geriatrics and hospice and palliative care for advanced cancer patients. The role of navigation for MBC patients is unique and should be designed to support the patient's many individual needs. Navigation requires assessment of individual knowledge deficit, coordination of care challenges, internal resource utilization, cultural requests, and emotional health. Navigation should also address the patient's financial and disability questions, medication assistance, symptom management, advanced care planning and goals of care discussions. Additional items to be discussed during navigation visits include primary care provider utilization, COVID-19 vaccination, illness and medication questions, and other patient questions as they arise. A comprehensive registry of MBC patient's medical records and histories will assist researchers in designing future therapeutic and quality of life clinical trials. The categories of patient demographics, clinical variables, pathological variables, treatment variables, outcomes of MBC, and PROs will create a robust registry. A comprehensive patient registry can create a rich database which can guide and inspire future innovative research. Peer support through support groups and peer-to-peer matching s pivotal to MBC patients finding and utilizing their patient voice, emotionally supporting each other and learning from other's similar experiences. Connection between patients and the creation of a community of survivors can empower patients to positively impact their care through self-advocacy and self-efficacy. Continuing patient education is also essential to providing quality cancer care. The format of a weekly virtual education webinars are helpful in creating an engaged patient community and a platform to disseminate educational resources in a reoccurring digestible format. Frequent educational webinars covering a wide variety of topics can positively influence patient interactions with their healthcare providers and influence how patients living with MBC view their own cancer experience. Educational webinars provide opportunities for patients to connect with subject matter experts, other patients like themselves, and share information with their family and friends. Informed patients can discuss and ask questions more confidently with their health care providers about information and services presented during the educational webinars. The symptom profile of patients living with MBC are impacted by numerous variables such as disease burden, treatment plan, comorbidities, supportive regimen etc. The collection of PROs has been shown to improve patient satisfaction with his/her care, improve quality of life, decrease emergency room visits and hospitalizations, and increased overall survival. The routine measurement and management of MBC patients' symptoms has been found to be integral in providing comprehensive cancer treatment. The collection of PROs improves patient and provider communication and elicits the outcome to symptoms that matter most to each patient. Patients diagnosed with MBC are living longer because of the recent advancements in therapeutic treatments. A multifaceted and comprehensive program consisting of therapeutic clinical trials, multidisciplinary specialty care, individualized patient navigation, peer support, continuing education, and PROs collection is integral to fully support patients living with MBC.

Accommodating ''History Effects'' in Long Duration, Multisite Clinical Trials to Ensure Relevant and Compelling Evidence

Over the course of a clinical trial, changes in the practice environment have the potential to reduce internal and external validity and impact change in patient outcomes. Such ''history effects''1 can take the form of changes in standard of care, clinical guidelines and recommendations, new drug/device availability in the marketplace, testing and screening procedures, and, as recently experienced, a global pandemic. Clinical trials conducted over many years are particularly susceptible to history effects. Such effects can impact foundational ability to continue a trial, including clinician equipoise and ability to implement trial interventions, necessitating awareness and action planning. For example, Curtis et al.2 acknowledged challenges with clinical guideline history effects and issued recommendations for addressing them such as consideration of participant wellbeing, stakeholder engagement, safety monitoring, review of guideline and policy changes, and development of rules for protocol changes. This session will explore how four multisite clinical trials conducted with VA Cooperative Studies Program sponsorship and coordination have weathered history effects during prolonged periods of enrollment. Topics to be covered include the implementation of pragmatic designs, monitoring of clinical guidelines, assessing control group treatment conditions, modifying protocols, adjusting quality assurance procedures, refining recruitment pathways, and training site investigators. The speakers, Study Chairs, will describe best practices and provide recommendations for navigating history effects in prolonged multisite clinical trials that can ensure outcomes remain relevant and compelling to inform public health at trial commencement. The CSP 2008/PTXRx study is a pragmatic, randomized, double-blind, placebo-controlled, multicenter clinical trial of Veteran patients with diabetic kidney disease (DKD) examining whether pentoxifylline (PTX), when added to usual care, can delay time to end-stage renal disease or death. Enrollment for the study began in 2019, and it is anticipated that 9 years of follow-up will be required to observe the required number of primary events. Given the long duration of the study, changes in clinical guidelines were anticipated and have occurred, including the approval of new DKD therapies and introduction of a new formula for estimated glomerular filtration rate (eGFR) calculation. In anticipation of these changes, the study design allows for whatever standard of care is extant at any time during the course of the study. PTXR's pragmatic trial design and protocol leverage the VA's research infrastructure and remote platforms allowing the study to be responsive to external changes and to safely continue during a global pandemic. The CSP 596/OPTION study is a randomized, double- blind, multicenter trial of Veteran patients with a first or second recurrent Clostridium difficile infection (CDI) comparing (1) fidaxomicin and (2) vancomycin, followed by a taper and pulse to (3) a standard vancomycin regimen. Since enrollment began in 2016, significant changes in CDI epidemiology and clinical management have impacted the study. The COVID-19 pandemic also resulted in an administrative hold on all trial activity followed by staggered reopening of sites due to variable COVID-19 activity and clinical priorities. Many clinical laboratories switched to algorithms that included free toxin assays in addition to polymerase chain reaction (PCR) tests out of concern for overdiagnosis based on PCR testing alone, reducing the number of potentially enrollable cases. There has been increased empirical vancomycin treatment for recurrent CDI without confirmation by stool testing, a requirement for enrollment, and a recruitment strategy for identifying potential cases. Finally, conflicting clinical guidelines for recurrent CDI has created potential equipoise when considering enrollment. Ongoing educational efforts have been made to clarify the protocol and emphasize the validity of the research question as well as protoco changes to allow safe enrollment and follow-up of participants in the face of the ongoing COVID-19 pandemic. The CSP 2005/VALOR is a phase III randomized, open label, multicenter clinical trial of Veteran patients with operable stage I non-small cell lung cancer that compares stereotactic radiotherapy and anatomic pulmonary resection with a primary outcome measure of overall survival. The study was activated in 2017 and recruitment to the trial has been affected by ongoing changes in public and clinician perceptions about stereotactic radiotherapy and surgery that have interfered with equipoise and willingness of participants to enroll. The study team perpetually addresses this challenge through group conversations with local site investigators, study coordinators, and other research personnel to preserve group equipoise across the study. Since the study's activation, new safety information about stereotactic radiotherapy has emerged necessitating protocol modifications while aiming to preserve internal and external validity. The includes modifying standard operating procedures for the study's centralized quality assurance program that has had to adapt its process to remain contemporary. STARPORT, funded by VA CSRD with CSP collaboration, is a randomized, open label, multicenter clinical trial of Veteran patients with oligorecurrent prostate cancer comparing the effects of standard systemic therapy (SST) alone or with PET-directed local therapy using surgery or radiation. Although enrollment was initiated in 2021, changes are already evident in clinical practice guidelines regarding the use of imaging in workup in this patient population. Shortly before the start of accrual, 18F-DCFPyL PSMA PET/CT received FDA-approval. Consequently, it is being rapidly adopted at the STARPORT VA medical centers and the use of conventional imaging using CT or bone scan prior to PET/CT imaging-part of the original eligibility criteria-quickly is falling out of favor. Furthermore, shortly after the start of enrollment, NCCN guidelines adopted the stance that conventional imaging was no longer required in the setting of PSMA PET/CT imaging, solidifying the transition away from conventional imaging. Thus, the protocol is being amended to remove the requirement for conventional imaging as part of workup for oligorecurrence. In addition, to be generalizable, the study is designed to integrate future PSMA radiotracers that are incorporated into practice as well as changes in SST regimens over the time of the study.

Recruitment, clinical equipoise, patient acceptance and compliance in the UK-ANZ POSNOC trial

Background: POSNOC is a UK-ANZ multicentre, non-inferiority, randomised trial comparing systemic therapy alone with systemic therapy plus Axillary Treatment (Axillary radiotherapy or ALND) for women with <=2 macrometastases at SNB. The primary outcome is axillary recurrence within 5 years. This paper describes screening, recruitment and compliance data. Method(s): Sites were requested on a monthly basis to upload screening data and provide reasons for nonrecruitment of eligible patients into the trial. Sites entered in the online database whether the patients were compliant with their randomisation allocation. Result(s): The study opened in July 2014 and completed target recruitment of 1900 women (24% of those screened) in July 2021, at 95 sites in the UK and 20 sites in Australia and New Zealand. The reason for non-enrolment was unknown in 1300 women. Of the remaining 4774 women with known reasons, who were screened but not randomised, the most common reasons for non-recruitment were due to either patients (n=2219, 46.5%) or their clinicians (n=782, 16.4%) favouring axillary treatment, or patients (n=490, 10.3%) or their clinicians (n=170, 3.6%) not wishing to have axillary treatment. Over the course of the study, there was an increase in the proportion of patients wanting axillary treatment and declining the trial (Mean % patients declined 2015 - 17.9%, 2021 - 39.1%). Mean number of participants recruited per site per month was 0.24 (SD 0.18) overall, 0.25 (SD 0.19) in the UK, and 0.19(SD 0.15) in ANZ. The mean was < 0.3 in 79 sites and >0.9 in only one site. Recruitment rate remained consistent throughout the study (mean 25.3 per month) except for during the first 6 months of recruitment (5.7) and during the COVID pandemic Apr-Sep 2020 (7.5). Of 89 (4.8%) participants non-compliant with allocation, n=45 (50.6%) received systemic therapy alone and n=44 (49.4%) received systemic therapy plus axillary treatment. There was no fluctuation in the direction of non-compliance during the study duration. There was increasing uptake of axillary radiotherapy to treat the axilla instead of ALND over the course of the study in patients receiving axillary treatment (Number who had ART of all who had axilla treatment2014-2017 - 248/454 (54.6 %);2018-2021 - 315/449 (70.2%)). Conclusion(s): Recruitment and compliance with randomised allocation remained consistent over a seven-year period. POSNOC with in-built radiotherapy QA will provide definitive data on axillary management in patients undergoing mastectomy or BCS with <=2 macrometastases on SNB.

Patient questionnaire-based triage improves outcomes for psoriasis referrals

COVID-19 has placed additional demands on a healthcare system that is already overstrained. While the National Health Service has coped extremely well in the face of new pressures, much of the pressure has transferred to a growing backlog of non-COVID outpatient care. Waiting lists have become unwieldy and new dermatology waiting times can be in excess of 18 months. We have developed a novel system to enable our tertiary referral dermatology department to triage rapidly and manage new patients with psoriasis, returning to target levels of activity, with minimum impact on patient care. Newly referred patients with psoriasis were sent a questionnaire, including the Dermatology Life Quality Index (DLQI), to direct their management appropriately. Patients were asked to estimate their affected body surface area using the palm measurements and affected body sites. Patients were also asked which treatment types they would be prepared to accept if offered (phototherapy, systemic therapy), as well as the type of clinic they would find acceptable. The latter included faceto- face only, telephone/video consultation or using a secure skin mobile phone app (MySkinSelfie), whereby photos are securely uploaded for viewing by the doctor but are still controlled by the patient. Of 265 patients, 222 responded (average response time 7 days). In total, 217 were offered an appointment. Thirty-one per cent were seen acutely (2 weeks) and the remainder in routine clinics. Two patients no longer wanted an appointment. An algorithm was used to place patients in appropriate clinics according to their responses. Patients who did not respond to the questionnaire within 4 weeks were sent a reminder letter and then discharged if there was still no reply (17%). Median DLQI was 15, with 63% of patients happy to have a telephone/video consultation, 72% were open to phototherapy, 80% were happy to use the MySkinSelfie App and 34% requested faceto- face appointments only. During the COVID-19 pandemic many dermatology units have had to limit the focus of their work on skin cancer, leaving little time for all but the most urgent patients with inflammatory disease. A previous systematic review and meta-analysis (Singh S, Taylor C, Kornmehl H, Armstrong AW. Psoriasis and suicidality: a systematic review and meta-analysis. J Am Acad Dermatol 2017;77: 425-40) of 1.7 million patients with psoriasis confirmed an increased risk of suicidal ideation [odds ratio (OR) 2.05] and suicidal behaviour (OR 1.26;Singh et al.), highlighting the importance of managing these patients in a timely manner. General practitioner letters can lack sufficient information on disease severity/ urgency, but our simple model allows the department to streamline referrals quickly, ensures that the patient still wants to be seen and minimizes unnecessary hospital visits. We propose that this approach is considered by other dermatology departments to streamline outpatient waiting lists and accelerate a return to normal activity during the pandemic.

Determinants of severe COVID-19 infection in Patients with Breast Cancer from a Community Oncology Practice in Brazil

Purpose: The SARS-CoV-2 pandemic was declared a global public health emergency. Determinants of mortality in the general population are now clear, but specific data on patients with breast cancer (BC) remain limited, particularly in developing nations. Material(s) and Method(s): We conducted a longitudinal, multicenter cohort study in patients with BC and confirmed SARS-CoV-2 infection. The primary end point was the proportion of patients on treatment for severe SARS-CoV-2 infection (defined as need for hospitalization) or early death (within 30 days of diagnosis). Data were evaluated sequentially in the following way: i) univariate Fisher's exact test;ii) multivariable logistic regression analysis;and iii) multivariable logistic regression. In items i and ii only those with P< 0.1 are considered significant and in stage iii only those with p< 0.05 were the final significant variables. We divided patients' data into three major variable domains: a) signs and symptoms;b) comorbidities;and c) tumor and treatment characteristics;in item ii each variable domain was tested separately, finally, in item iii the significant variables of all domains were tested together and we called it the integrative step. Result(s): From April 2020 to June 2021, 413 patients with BC and COVID-19 were retrospectively registered, of which 288 (70%) had an identified molecular subtype and 273 (66%) had stage information. Most patients were on active systemic therapy or radiotherapy (73.2%), most of them in the curative setting (69.5%). The overall rate of severe SARS-CoV-2 was 19.7% (95% CI, 15.3-25.1). In the integrative multivariate analysis, factors associated with severe infection were metastatic setting, chronic pain, acute dyspnea, and cardiovascular comorbidities. Recursive partitioning modeling used acute dyspnea, metastatic setting, and cardiovascular comorbidities to predict nonprogression to severe infection, yielding a negative predictive value of 84.9% (95% CI, 78.9%-88.3%). Conclusion(s): The rate of severe COVID-19 in patients with BC is influenced by prognostic factors that partially overlap with those reported in the general population. High-risk patients should be considered candidates to active preventive measures to reduce the risk of infection, close monitoring in the case of exposure or SARS-CoV-2 -related symptoms and prophylactic treatment once infected.

Exploration on rationalization of diagnosis and treatment of breast cancer patients combined with COVID-19.

Coronavirus disease 2019 (COVID-19) has become a major global public health event as a new acute respiratory infectious disease. During the COVID-19 pandemic, compared with the healthy population, cancer patients had a higher risk of developing comorbidities of other systems, due to their bad poor immunity and older age. Research showed that breast cancer, as a malignant disease, had the highest disease incidence in female patients. Breast cancer patients with COVID-19 infection often have worse prognosis, and they have to postpone anti-tumor treatment due to COVID-19 infection. At present, the effect of delayed treatment on the survival rate of breast cancer patients is unclear, and whether the treatment plan of these patients should be adjusted is still being studied. Through the systematic review of existing clinical research studies, the guidelines of various societies and the expert consensus, this paper reviews the selection and rationalization of breast cancer treatment options under the COVID-19 epidemic, and discusses the opportunity and approaches of anti-tumor treatment for breast cancer patients infected with COVID-19.Copyright © 2022 Editorial Department of Journal of Shanghai Second Medical University. All rights reserved.

Main reasons of choice of formulation and route of triptorelin treatment initiated in patients with prostate cancer (PCa): TALISMAN study

Background: Modalities of use of androgen deprivation therapy (ADT), like triptorelin, in real life, at the era of new strategies in advanced stages, lack of recent data. Our purpose here was to describe main reasons of choice of formulation and route (F&R) of triptorelin treatment (Tt) declared by the physician. Patient comorbidities, cancer aggressiveness and physician habits may influence their choices. Method(s): Initiated in 2020, a prospective, multicenter, non-interventional study is ongoing in France (TALISMAN, NCT04593420). Patients with histologically confirmed PCa, eligible for >= 12-month triptorelin Tt within its label were enrolled. Interim analysis of baseline data was planned when 50% of 786 planned patients were enrolled. Modalities of use, including F&R of triptorelin prescribed [monthly intramuscular (1mIM), every 3 months subcutaneous (3mSC) or intramuscular (3mIM), every 6 months intramuscular (6mIM)], were described. Result(s): 509 patients were included in the interim analysis. Overall population was presented at ASCO-GU22. Subgroups of F&R are presented here. Main F&R prescribed was 3mSC (70.7%). Main baseline parameters in F&R subgroups are presented (except for 1mIM, 4 patients (0.8%)). 31 patients had missing F&R data and were not included in subgroups. 62.1% of patients overall received at least one concomitant systemic Tt for comorbidity at baseline (58.2% in 3mIM, 61.7% in 3mSC and 6mIM). 18.6% and 13.0% of patients overall received, respectively, platelet aggregation inhibitor and anticoagulant;they were 20.9% and 13.8% in 3mSC, 7.3% and 5.5% in 3mIM, 18.5% and 11.1% in 6mIM. Conclusion(s): Main reason of choice of F&R of triptorelin was physician preferred F&R (47.7%);noticeable reasons included anticoagulants for the choice of 3mSC, planned total duration of Tt for 3mIM and 6mIM, and potential impact on compliance for 6mIM. As the covid pandemic may change the management of patients with prostate cancer, longer acting formulations may become more attractive.

Expert guidance on overall management of liver cancer during the COVID-19.

The pandemic of Corona Virus Disease 2019 (COVID-19) continues, which shows the concentrated or sporadic cases in multiple places. Current COVID situation is still complex. During the COVID-19, routine diagnosis and treatment of liver cancer patients has been affected in different degrees. Under the premise of following the treatment guidelines, how to reduce the risk of infection of patients and medical staff, utilize limited medical resources to maximally ensure anti-tumor treatment and related emergency treatment, and help patients get through the epidemic period is a problem for liver oncologists. Thus, experts of liver cancer treatment related disciplines of Zhongshan Hospital, Fudan University have written the Expert guidance on overall management of liver cancer during the COVID-19, which aims to provide references for liver oncologists to conduct clinical work safely and effectively under the epidemic prevention and control, and to help patients fight against the epidemic smoothly.Copyright © 2022 Chinese Medical Journals Publishing House Co.Ltd. All rights reserved.

Management of patients with advanced prostate cancer-metastatic and/or castration-resistant prostate cancer: Report of the Advanced Prostate Cancer Consensus Conference (APCCC) 2022.

BACKGROUND: Innovations in imaging and molecular characterisation together with novel treatment options have improved outcomes in advanced prostate cancer. However, we still lack high-level evidence in many areas relevant to making management decisions in daily clinical practise. The 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) addressed some questions in these areas to supplement guidelines that mostly are based on level 1 evidence. OBJECTIVE: To present the voting results of the APCCC 2022. DESIGN, SETTING, AND PARTICIPANTS: The experts voted on controversial questions where high-level evidence is mostly lacking: locally advanced prostate cancer; biochemical recurrence after local treatment; metastatic hormone-sensitive, non-metastatic, and metastatic castration-resistant prostate cancer; oligometastatic prostate cancer; and managing side effects of hormonal therapy. A panel of 105 international prostate cancer experts voted on the consensus questions. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The panel voted on 198 pre-defined questions, which were developed by 117 voting and non-voting panel members prior to the conference following a modified Delphi process. A total of 116 questions on metastatic and/or castration-resistant prostate cancer are discussed in this manuscript. In 2022, the voting was done by a web-based survey because of COVID-19 restrictions. RESULTS AND LIMITATIONS: The voting reflects the expert opinion of these panellists and did not incorporate a standard literature review or formal meta-analysis. The answer options for the consensus questions received varying degrees of support from panellists, as reflected in this article and the detailed voting results are reported in the supplementary material. We report here on topics in metastatic, hormone-sensitive prostate cancer (mHSPC), non-metastatic, castration-resistant prostate cancer (nmCRPC), metastatic castration-resistant prostate cancer (mCRPC), and oligometastatic and oligoprogressive prostate cancer. CONCLUSIONS: These voting results in four specific areas from a panel of experts in advanced prostate cancer can help clinicians and patients navigate controversial areas of management for which high-level evidence is scant or conflicting and can help research funders and policy makers identify information gaps and consider what areas to explore further. However, diagnostic and treatment decisions always have to be individualised based on patient characteristics, including the extent and location of disease, prior treatment(s), co-morbidities, patient preferences, and treatment recommendations and should also incorporate current and emerging clinical evidence and logistic and economic factors. Enrolment in clinical trials is strongly encouraged. Importantly, APCCC 2022 once again identified important gaps where there is non-consensus and that merit evaluation in specifically designed trials. PATIENT SUMMARY: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with healthcare providers worldwide. At each APCCC, an expert panel votes on pre-defined questions that target the most clinically relevant areas of advanced prostate cancer treatment for which there are gaps in knowledge. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients and their relatives as part of shared and multidisciplinary decision-making. This report focuses on the advanced setting, covering metastatic hormone-sensitive prostate cancer and both non-metastatic and metastatic castration-resistant prostate cancer. TWITTER SUMMARY: Report of the results of APCCC 2022 for the following topics: mHSPC, nmCRPC, mCRPC, and oligometastatic prostate cancer. TAKE-HOME MESSAGE: At APCCC 2022, clinically important questions in the management of advanced prostate cancer management were identified and discussed, and experts voted on pre-defined consensus questions. The report of the results for metastatic and/or castration-resistant prostate cancer is summarised here.

The Feasibility of Providing Remote Functional Family Therapy with Adolescents During the COVID-19 Pandemic: A Mixed-Method Study.

Background: Due to the recent COVID-19 pandemic, mental health care has largely transferred its services to online platforms, using videoconferencing (VC) or teletherapy. Within the field of family therapy, however, there is little evidence on the feasibility of using VC, especially when working with whole families at the edge of care. Objective: This study investigated the feasibility of remote Functional Family Therapy (FFT), using a mixed-method approach. Method: Study 1 consisted of semi-structured interviews with 23 FFT professionals (18 female) about their experience of providing remote FFT during the COVID-19 pandemic. Study 2 included monitoring data of 209 FFT clients (46% female, M age = 14.00) who participated in FFT during the pandemic. We compared families who received mainly in-person, mainly remote or a mix of remote and in-person on client-reported alliance, drop-out, therapist-rated outcomes, and treatment intensity using MANCOVA's and chi-square tests. Results: In Study 1 two themes emerged around experienced challenges, namely 'Feeling in control' and 'Engagement and alliance'. Two other themes emerged around adaptations, namely 'Being more on top' and 'Connecting in different ways'. In Study 2, we found that the therapeutic alliance was not related to using VC. Also, families had less between-session contact during the Engagement and Motivation Phase when receiving mainly VC, but had more sessions and longer therapy when receiving a mix of in-person and remote therapy. Conclusions: The current study suggests that providing systemic family teletherapy to families on the edge of care is feasible. Further development of systemic family teletherapy is warranted. Supplementary Information: The online version contains supplementary material available at 10.1007/s10566-022-09692-y.

Oncological emergencies

The incidence of cancer continues to rise, with an estimated 1 in 2 of the UK population born after 1960 diagnosed with malignancy at some point during their lifetime. This is in the context of an ageing population with increasing multimorbidity and polypharmacy. Cancer patients are frequent users of emergency care services and have a high rate of ambulance conveyance and hospital admission after review in emergency departments. Presentations can be a consequence of the cancer, its treatment or coexistent morbidity. Given the expanding armamentarium of cancer therapies, acute and general physicians are faced with a myriad of complex issues and require a knowledge of the broad principles of initial assessment, initial management and timely access to the wider multi-professional cancer team. © 2022