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Objectives: To evaluate how payers utilize Institute for Clinical and Economic Review (ICER) assessments to inform coverage or formulary decisions. Method(s): Double-blinded, web-based survey was fielded through Xcenda's research panel, the Managed Care Network, from June to July 2022. Result(s): A total of 51 payers from health plans (n=27), integrated delivery networks (n=12), and pharmacy benefit managers (n=12) participated in the survey. When assessing the usefulness of ICER's value assessment framework (VAF) to inform formulary decisions within their organizations, 57% of payers indicated it was extremely/very useful, 33% indicated somewhat useful, and 10% indicated not at all/not very useful. Most respondents (73%) agreed that ICER assessments are aligned with their organization's internal assessment. Utilization of ICER's VAF was most prevalent in high-cost drug or disease states (78%), rare/orphan disease states (71%), and oncology/hematology disease states (67%). Payers reported less use in primary care disease states (29%), COVID-19 (8%), and digital therapeutics (4%). In the last 24 months, 20% of payers reported ICER's recommendations often influenced coverage decisions, 59% indicated occasional influence, and 22% indicated no influence. In the last 24 months, payers indicated the top 5 ICER assessments that influenced their coverage decisions included high cholesterol (38%), Alzheimer's disease (36%), atopic dermatitis (33%), multiple myeloma (31%), and chemotherapy-induced neutropenia (28%). ICER assessments that were less impactful included beta thalassemia (3%), digital health technologies (3%), and supervised injection facilities (3%). Payers reported using ICER assessments to inform both expanded and restricted coverage decisions. Conclusion(s): Payers find ICER's VAF useful to inform their organization's formulary decisions. ICER's assessments often align with payers' internal assessments and are most frequently utilized for high-cost drugs or disease states. Payers indicate ICER assessments have affected both expansion and restriction in their coverage policies.Copyright © 2023
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The TG6002.03 trial is a dose-escalation phase 1 clinical trial of TG6002 infusion via the hepatic artery in patients with liver-dominant colorectal cancer metastases. TG6002 is an engineered Copenhagen strain oncolytic Vaccinia virus, deleted of thymidine kinase and ribonucleotide reductase to enhance tumor selective viral replication and expressing FCU1, an enzyme converting the non-cytotoxic prodrug 5-fluorocytosine (5-FC) into the chemotherapeutic compound 5-fluorouracil (5-FU). In this trial, patients with advanced unresectable liver-dominant metastatic colorectal cancer who had failed previous oxaliplatin and irinotecan-based chemotherapy were treated with up to 2 cycles of TG6002 infusion 6 weeks apart via the hepatic artery on day 1 combined with oral 5-FC on days 5 to 14 (where day 1 = TG6002 infusion). TG6002 infusion was performed over 30 minutes via selective catheterization of the hepatic artery proper. 5-FC oral dosing was 50mg/kg x4 daily. Blood was sampled for TG6002 pharmacokinetics and 5-FC and 5-FU measurements. Sampling of liver metastases was performed at screening and on day 4 or day 8 for virus detection and 5-FC and 5-FU quantification. In total, 15 patients (median age 61 years, range 37-78) were treated in 1 UK centre and 2 centres in France and received a dose of TG6002 of 1 x 106 (n=3), 1 x 107 (n=3), 1 x 108 (n=3), or 1 x 109 pfu (n=6). Fourteen of the 15 patients received a single cycle of treatment, including one patient who did not received 5-FC, and one patient received two cycles. TG6002 was transiently detected in plasma following administration, suggesting a strong tissue selectivity for viral replication. In the highest dose cohort, a virus rebound was observed on day 8, concordant with replication time of the virus. In serum samples, 5-FU was present on day 8 in all patients with a high variability ranging from 0.8 to 1072 ng/mL and was measurable over several days after initiation of therapy. Seven of the 9 patients evaluable showed the biodistribution of the virus in liver lesions by PCR testing on day 4 or day 8. Translational blood samples showed evidence for T-cell activation and immune checkpoint receptor-ligand expression. At 1 x 109 pfu, there was evidence for T-cell proliferation and activation against tumour-associated antigens by ELISpot and for immunogenic cell death. In terms of safety, a total of 34 TG6002-related adverse events were reported, of which 32 were grade 1-2 and 2 were grade 3. The maximum tolerated dose was not reached, and a single dose-limiting toxicity was observed consisting of a myocardial infarction in a context of recent Covid-19 infection in a 78-year-old patient. These results indicate that TG6002 infused via the hepatic artery in combination with oral 5-FC was well tolerated, effectively localized and replicated in the tumor tissues, expressed its therapeutic payload and showed anti-tumoral immunological activity.
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Objectives: The COVID-19 pandemic has disrupted healthcare delivery for patients with cancer. This research assessed the impact of COVID-19 on the delivery of cancer care in the US during the pandemic and evaluated emerging treatment trends in the post-COVID-19 setting. Method(s): A series of Community Oncology Research Evaluations (CORE) meetings were conducted across the US between December 2021 and May 2022. During these meetings, community oncologists undertook a survey focused on the impact of COVID-19 in the community-practice setting. Result(s): 242 community oncologists participated in the survey. Over 80% of the physicians estimated that up to 20% of patients with cancer have gone undiagnosed due to their reluctance to visit a healthcare provider during the pandemic. More than half (51%) of community oncologists reported a decrease of up to 50% in in-office patient visits versus before COVID-19, with most physicians (71%) indicating that some delivery of care changed to a virtual setting in up to 20% of patients. Most physicians (86%) reported no change in their willingness to assess new therapies. Most common strategies to manage cancer during the pandemic included the use of telemedicine for stable patients receiving oral chemotherapy (55%), use of extended dosing schedules (39%), and switching route of chemotherapy administration from intravenous to oral or subcutaneous (38%). Once COVID-19 is under control, these strategies are expected to remain in place. Nearly half of the community oncologists (48%) plan to continue using telemedicine for managing disease in stable patients receiving oral chemotherapy, over a quarter intend to continue using extended dosing schedules, and 19% plan to use oral or subcutaneous chemotherapy when appropriate. Conclusion(s): COVID-19 had a detrimental impact on cancer diagnosis and delivery of therapy. Community oncologists reported a seemingly permanent shift in care patterns including telemedicine, extended dosing schedules, and switching chemotherapy administration route.Copyright © 2023
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Introduction: Despite several studies, the impact of coronavirus disease 2019 on patients with multiple myeloma remains uncertain. Material(s) and Method(s): We performed a survey that covered the period of the first and second waves of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in 23 centers inseven countries. Out of 352 patients with myeloma and SARS-CoV-2, 23% died. Results/Conclusions: Logistic regression showed a lower risk of death among patients treated with proteasome inhibitor and a higher risk of death for those who had a severe or a very severe course of disease.Copyright © 2023 Sciendo. All rights reserved.
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Background: Patients with cancer are at a higher risk of getting infected with the severe acute respiratory syndrome coronavirus 2 owing to their immunocompromised state. Providing care to these patients amidst the first wave of the coronavirus disease-2019 (COVID-19) pandemic was extremely challenging. Objective(s): This study was aimed at evaluating the clinical profile and disease-related outcomes of pediatric patients with hematological illnesses and cancer. Material(s) and Method(s): This retrospective study was conducted at a tertiary care center in North India during the first wave of the pandemic from March 2020 to December 2020. Children aged up to 18 years, who were treated for a hematological illness or malignancy or underwent hematopoietic stem cell transplantation (HSCT) and tested positive for COVID-19 regardless of symptoms were included in the study. Baseline demographic data related to the age, diagnosis, treatment status, and chemotherapy protocol used were collected. Outcomes including the cure rates, comorbidities, and sequelae were recorded. Result(s): A total of 650 tests for COVID-19 were performed for 181 children;22 patients were found to be COVID-19 positive. The most common diagnosis was acute leukemia (63.6%). None of the patients developed COVID-19 pneumonia. The majority of patients had asymptomatic infection and were managed at home. Among those with a symptomatic infection, the most common symptoms were fever and cough. A total of 3 (13.6%) patients needed oxygen therapy, one developed multisystem inflammatory syndrome of children leading to cardiogenic shock. Three patients required intensive care or respiratory support;all the patients had favorable clinical outcomes. The median time from the onset of COVID-19 to a negative result on the reverse transcription-polymerase chain reaction test was 21.3 days. Cancer treatment was modified in 15 patients (68.2%). Conclusion(s): Our results suggest that children with hemato-oncological illnesses rarely experience severe COVID-19 disease. The impact of the first wave of COVID-19 primarily manifested as disruptions in the logistic planning and administration of essential treatment to these children rather than COVID-19 sequelae.Copyright © 2021 Cancer Research, Statistics, and Treatment Published by Wolters Kluwer - Medknow.
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Objectives: To present a series of immunosuppressed patients (oncohematological disease, congenital immunosuppression, hematopoietic stem cell (HSCT), and solid organ transplant) assisted on ECMO. Method(s): Descriptive, retrospective study (2011-2020) of a cohort of 9 immunosuppressed patients, supported on ECMO. Medical records were reviewed and demographic, clinical, and analytical variables were collected. Result(s): In our series of 9 patients, 5 were male, the median age was 8 years [RIC 3-11 years]. Considering the underlying disease, 6 were oncologic, 1 liver transplant and 2 with congenital immunodeficiency after HSCT. 4 were under active chemotherapy (median 6 days after the last cycle [RIC 5-188]). 6 were admitted due to acute respiratory failure, 3 due to hemodynamic instability (3/9), (one septic shock). The median PEEP was 12 [RIC 9-15] and FiO2 100% (81-100%). 78% (6) required vasoactive drugs (median inotropic score 35 [RIC 0-75]. 40%. 5 had severe neutropenia and/or plateletopenia in the 24 hours prior to ECMO, and alterations in acid-base balance (median pH 7. 1 [RIC 6.9-7.15]. 5 were on multiorgan failure. TPrimary ECMO transport was performed in 4 patients (44%). Cannulation was peripheral in 80% (57% cervical, 43% femoral) and central in 20%;70% VA-ECMO. Median time of assistance was 15 days [RIC 3.5-31.5] in cardiac ECMO (4), and 29 days [RIC 13.5-42] and in pulmonary ECMO (n=5). The median total time of admission was 45 days [RIC 27-59]. 9 had an infection, 2 COVID after HSCT, and 8 bleeding complications, but only one required surgical revision. Renal replacement therapy was used in 5 (median 9 days [RIC 5-34.5]). Other therapies used were polymyxin hemadsorption(2), intratracheal surfactant(2), plasma exchange(1), infusion of mesenchymal cells(1) and specific memory T lymphocytes(2). 4 patients died, 5 survived decannulation, 2 died later, with an overall survival rate to hospital discharge of 33% (3/9). Conclusion(s): Despite having a worse prognosis, ECMO can increase survival in immunosuppressed patients, in situations that are challenging and require a multidisciplinary approach.
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The World Health Organization declared coronavirus infectious disease-2019 (COVID-19) linked to the severe acute respiratory syndrome (SARS-CoV-2), a global pandemic in March 2020. The pandemic outbreak has led to the most unprecedented and catastrophic loss of human life in the recent history. As of January 2021, there were more than 100 million cases of COVID-19 and more than two million deaths worldwide. Compared to the general population, patients with cancer are at a higher risk of poor outcomes from COVID-19. In large cohort studies, mortality from COVID-19 in patients with cancer can be as high as 40%. In addition to clinical variables (older age, male sex, and co-morbidities) that are associated with mortality in general population, cancer patients are uniquely vulnerable to severe COVID-19 due to immunosuppression from cancer and its therapy, and disruption of routine clinical care. Among patients with cancer, the lung cancer population is at a higher risk of poor outcomes and mortality from COVID-19 for several reasons. For instance, lung is the main target organ in COVID-19 that can lead to respiratory failure, patients with lung cancer have baseline poor lung function from chronic obstructive pulmonary disorder and smoking. In addition, some of the lung cancer treatment side-effects like pneumonitis, may obscure the diagnosis of COVID-19. In this article, we systematically review the most impactful cohort studies published to date in patients with cancer and COVID-19. We describe the rates of mortality in patients with cancer and COVID-19 with a special focus on the lung cancer population. We also summarize the factors associated with poor outcomes and mortality in patients with lung cancer and COVID-19.Copyright © The Author(s) 2021.
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Introduction: Mucinous adenocarcinomas of the appendix are defined as epithelial neoplasms often causing cystic dilation of the appendix due to accumulation of gelatinous material. Pseudomyxoma peritonei is an extremely rare complication of appendiceal mucinous adenocarcinomas with an estimated incidence rate of one to 2 people per million per year. Here-in we present a unique case of enterocutaneous fistula formation secondary to percutaneous biopsy of an enlarging omental mass in the setting of pseudomyxoma peritonei. Case Description/Methods: A 50-year-old male with a past medical history of metastatic appendiceal mucinous adenocarcinoma presented to the ED with abdominal pain, nausea, and vomiting. The patient had previously undergone 2 debulking surgeries over the past 2 years prior to admission and has since been on FOLFOX therapy. Due to the COVID pandemic, the patient did not follow-up in the 2 years period from previous admission. A CT scan was now notable for a new enlarging omental mass despite the recent debulking surgery. Given the enlarging mass, a decision was made to pursue a percutaneous biopsy of the mass due to concern for potential new malignancy. Two weeks after the biopsy, the patient presented to our facility due to worsening erythema and drainage from the biopsy site. The patient met SIRS criteria, thus broad-spectrum antibiotics were initiated. A CT of the abdomen and pelvis with oral and IV contrast was obtained, which demonstrated a 9 cm abscess or continuation of intra-abdominal multilocular cystic lesion/ pseudomyxoma peritonei. The surgical team was consulted. Patient had 100 cc of purulent and mucinous drainage expressed from biopsy site. The patient was then placed for transfer to a hospital capable of advanced surgical management for evaluation and potential resection of fistula formation. The patient had a successful reductive surgery and intraoperative chemotherapy (Figure). Discussion(s): Given the rarity of pseudomyxoma peritonei, appropriate management is not always straightforward. A literature review yielded no previous reports of enterocutaneous fistula as a complication of percutaneous drainage in the setting of pseudomyxoma peritonei. We recommend that percutaneous drainage not be sought in individuals with this diagnosis due to potential for fistula formation.
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Introduction. Primary mediastinal lymphoma (PML) is an aggressive lymphoid tumor treatment success of which is determined by induction therapy. To date, none of the standard chemotherapy regimens (CT) have demonstrated an advantage in efficacy. Intensive therapy programs are associated with high toxicity. Aim - to evaluate the efficacy and toxicity of two pilot prospective treatment protocols PML-16 and PML-19 as well as the possibility of using the analysis of freely circulating tumor DNA (ctDNA) to assess MRD in patients with PML. Materials and methods. From January 2016 to January 2022, 34 previously untreated PML patients were included in the study;average age - 32;stage > I - in 60 %;extramediastinal lesions - in 14.7 %;bulky disease - in 73.5 % of patients. Positron emission tomography combined with computed tomography (PET-CT) was performed;ctDNA was determined to assess the completeness of remission. Results. Eighteen patients received treatment according to the PML-16 protocol (6 courses of chemotherapy;2 blocks of RmNHL-BFM-90 + 4 courses of R-EPOCH). After the end of therapy, all 18 patients achieved PET-negative remission. The next 16 patients received treatment according to the PML-19 protocol (4 courses of chemotherapy;2 blocks of R-mNHL-BFM-90 + 2 courses of R-EPOCH) in combination with lenalidomide. After the end of therapy, 9 (56 %) patients achieved PET-negative remission;7 (44 %) retained pathological activity (D4-5 points). After 3 and 6 months 15 (94 %) patients achieved normalization of metabolic activity. Considering the high frequency of false-positive results in patients with PML, a ctDNA study was performed to determine the depth of remission in 15 patients. After the end of therapy, all 15 patients had complete elimination of ctDNA. Of these, 5 (33 %) remained PET-positive at the end of treatment. During further observation, after 3-6 months, in 4 patients the level of metabolic activity decreased to physiological without the use of consolidating therapy. After the end of therapy, one patient suffered the new coronavirus infection, COVID-19. A month later, residual formation of SUVmax 14.2 remained in the mediastinum. The patient is currently under observation. With a median follow-up of 36 months (9 to 76 months) all 34 patients are in remission. Conclusion. The effectiveness of PML-16 made it possible to abandon the consolidation therapy and refuted the idea of the need for 6 courses of CT. The combination of programs based on the application of the principle of high-dose short-pulse induction of remission (R-mNHL-BFM-90) in combination with the prolonged administration of medium doses (R-EPOCH) was crucial in achieving a successful result. The inclusion of lenalidomide in the "PML-19" program made it possible to achieve complete remission in 100 % of cases after 4 courses. The possibility of using DNA analysis to assess MRD in patients with PML was shown.Copyright © 2022 Izdatel'stvo Meditsina. All rights reserved.
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Introduction: Mucosa-associated lymphoid tissue (MALT) lymphomas are extra-nodal marginal zone B-cell lymphomas, most commonly found in the stomach, associated with Helicobacter pylori infections, and generally not linked with inflammatory bowel disease. Rectal MALT lymphoma is very uncommon and often associated with painful defecation, change in bowel habits, or rectal pressure/prolapse. Here, we present a rare case of an asymptomatic female with ulcerative colitis (UC) found to have benign-appearing rectal polyps during a routine screening colonoscopy. Case Description/Methods: The patient is a 56-year-old female with a history of left-sided UC, diagnosed in 1993, with one flare after receiving the 2nd dose of the Moderna COVID-19 vaccine, taking oral Olsalazine 500 mg twice daily, low-dose Prednisone, and mesalamine suppositories as needed presenting for screening colonoscopy. The patient was asymptomatic, citing regular non-bloody bowel movements and normal stool consistency. Colonoscopy revealed two 7 mm sessile, non-bleeding rectal polyps, surrounded by congested, erythematous, friable, and ulcerated mucosa in the rectosigmoid colon. Cold forceps biopsies were taken. Hematopathology evaluation of the routine colon biopsy samples revealed chronic nonspecific colitis while pathology of the rectal polyps showed marked lymphoplasmacytic infiltrate and extra-nodal marginal zone lymphoma of MALT. Ancillary studies, immunohistochemistry, and molecular studies for B-cell gene rearrangement confirmed extra-nodal marginal zone lymphoma of MALT with prominent plasmacytic differentiation. The patient was informed and close follow-up in Gastroenterology clinic was arranged. (Figure) Discussion: Rectal MALT lymphoma is rare with unclear management options. Treatments of UC include watchful waiting, surgical resection, endoscopic mucosal resection, radiation, and/or chemotherapy. Helicobacter pylori infections, though strongly linked with gastric MALT lymphoma, have not been shown to be strongly correlated with rectal MALT lymphoma. Given that patients with UC have chronic UCassociated colonic inflammation, lymphoma is often difficult to distinguish visually during colonoscopy, frequently masked by ulcerations and pseudo-polyps. In cases like these, more definitive treatments such as surgical resection could therefore be warranted. Long-term follow-up data is sparse and definitive management remains a clinical conundrum, thus these patients require reliable long-term multidisciplinary close follow-up. (Figure Presented).
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Introduction: Extensive stage small cell lung cancer (ES-SCLC) is the most aggressive form of lung cancer, and delays in treatment result in worse outcomes. The National Lung Cancer Audit1 guidelines advise 70% of patients should receive systemic treatment and 80% within 14 days of pathological diagnosis. We aimed to assess compliance with these recommendations and improve the treatment pathway for patients with ES-SCLC in East London. Method(s): To establish baseline metrics, we reviewed compliance with these guidelines in all patients diagnosed with ES-SCLC in 2019 (pre-COVID pandemic). Two interventions were made: i) admission of all newly diagnosed patients for urgent chemotherapy to improve time to treatment and ii) all newly diagnosed ES-SCLC patients across our network of five hospitals were requested to be reviewed by or transferred under a lung oncologist to improve treatment rates. We re-evaluated data from all ES-SCLC patients diagnosed in 2022 using the same pre-intervention criteria. Result(s): 31 patients in 2019 and 17 patients in 2022 were included. There was no significant difference in baseline characteristics including (median) age (68 vs 70, p=0.64), co-morbidities (1 vs 1, p=0.12), and performance status (1 vs 1, p=0.86) between cohorts. There was a significant decrease in the median [range] time to treatment (13 [4-80] days vs 4 [1-31] days, p=0.03] and an increase in the proportion of patients reviewed by a lung oncologist (74% to 100%, p=0.04). There was also an increase in the proportion of patients receiving treatment (61% vs 77%). [Figure presented] Conclusion(s): Our data suggest that these interventions may improve the proportion of patients receiving treatment and the time to treatment. Larger local audits and correlation with national data is required to evaluate the impact these interventions have on outcomes. Reference: [1] RCP National Lung Cancer Audit Annual Report. 2022. Disclosure: No significant relationships.Copyright © 2023 Elsevier B.V.
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Introduction: Due to lockdown measures associated with the COVID 19 pandemic (1), there were substantial changes to healthcare delivery, including the suspension of face-to-face medical appointments, expansion of telehealth and changes to medication protocols.(2) It is important to learn from the successes and challenges of this period to ensure we adapt and improve how we support people to take medicines in the future. Aim(s): We sought to conduct a systematic review to explore the different approaches used to deliver medicines management services for people living with long term conditions (LTCs) during the pandemic and identify strategies that could be integrated into standard care. Method(s): We conducted a systematic review across 3 large databases: MEDLINE (OVID), EMBASE (OVID) and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Our research question and search strategy was developed using the PICO framework (Population: adults with LTCs, Intervention: medicines management during the COVID 19 pandemic;no comparison group. Outcome(s): any aspect relating to medicines management. Search terms relating to 'long term conditions', 'medication management' and 'COVID-19' were used. One reviewer (LM) screened all titles, s, and full texts. We included studies discussing medication management of LTCs, in patients of all ages and healthcare settings, throughout the pandemic. Primary literature sources, feasibility studies and case studies, were included. We excluded studies solely focusing on disease monitoring, or the treatment of COVID/ 'long Covid'. One reviewer performed a thematic analysis, synthesising the findings into themes and sub-themes, which were discussed with a further reviewer (CT). A critical appraisal was performed using the Critical Appraisal Skills Programme checklists. Result(s): The search returned 2365 results. After deduplication, articles were removed at the title (n=1070) (n=813) and full text (n=232) stages. 31 studies were included. Studies were conducted in India (n=6), US (n=5), international (n=4), France (n=2), Italy (n=2), and one each from China, Japan, Jordan, Mexico, Morocco, Nigeria, Romania, Saudi Arabia, Spain, UK, UK and US, and location not specified. Most studies (n=17) employed subjective methods of data collection (surveys/ questionnaires). We identified 6 themes. These were: changes in consultation type, for instance using teleconsultations and smartphone apps to monitor glucose control and diabetic management. Studies described temporary changes to treatment protocols e.g., using oral chemotherapy to reduce the need for in-person appointments and reduce the infection risk associated with intravenous administration. Control of certain conditions for example epilepsy was reduced in some studies. Patients missed doses due to drug shortages associated with disruptions in the medication supply chain, particularly in low-income countries. Finally, we identified prescribing trend changes in certain classes of medicines (e.g. reduced biologic usage due to immunosuppression risk) and an increase in patients self-medicating conditions including anxiety and depression, with associated safety risks. Conclusion(s): This review suggested that certain medical conditions such as diabetes and hypertension were more suited to remote monitoring with technological interventions such as smartphone apps. While other conditions e.g., cancer and epilepsy, demonstrated a greater need for in-person care. Countries of lower socioeconomic status were disproportionately affected by the pandemic.
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Introduction/Aim: Patients with interstitial lung disease (ILD) are at higher risk of COVID-19 infection associated morbidity and mortality, and hence may benefit from early anti-viral therapy. The access criteria for early oral anti-viral therapies for COVID-19 varied in early 2022 due to limited supplies nationally. We created a live clinical database of ILD patients in a tertiary hospital setting, stratifying them by measurable risk factors and therefore accessibility by state or national criteria to anti-viral therapy. Method(s): A list of active ILD clinic patients was generated from the WEBPAS clinic database. Data on patient demographics, co-morbidities and immunosuppressive medications relevant to access to anti-viral medications via the PBS criteria and state-based criteria was gathered by medical records review. Demographic information included age, BMI, ethnicity, residential care living and rurality. Co-morbidity risk factors included congestive cardiac failure, neurological disease, diabetes mellitus, chronic kidney disease, liver cirrhosis, chronic lung disease and immunodeficiencies. Medications of relevance included glucocorticoids, steroid-sparing immunomodulators and chemotherapy. Combinations of the above risk factors equate to eligibility to treatment. Result(s): Between the data capture dates of 1 February 2021 and 31 January 2022, 526 patients were identified. Of these 457 fit the inclusion criteria. Median age was 71.4 years (range 20-92), ratio of F:M was 1.09. 11% of patients were on long term oxygen therapy. Commonest conditions were idiopathic pulmonary fibrosis (26.3%), connective-tissue disease ILD (18%) and sarcoidosis (13.4%). 92 (20%) of patients fit into 'moderate or severely immunocompromised' criteria. 346 (75%) of patients fit criteria for early anti-virals by the first iteration of PBS criteria. Using the second iteration of PBS criteria, 374 (82%) of the ILD patients fit criteria for early anti-viral treatment. Notably, some patients qualify for anti-virals on multiple eligibility PBS criteria. Conclusion(s): A large proportion of our ILD cohort is deemed 'high risk' for COVID-19 morbidity and would qualify for early anti-viral therapies (regardless of vaccination status).
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Introduction. Primary mediastinal lymphoma (PML) is an aggressive lymphoid tumor treatment success of which is determined by induction therapy. To date, none of the standard chemotherapy regimens (CT) have demonstrated an advantage in efficacy. Intensive therapy programs are associated with high toxicity. Aim - to evaluate the efficacy and toxicity of two pilot prospective treatment protocols PML-16 and PML-19 as well as the possibility of using the analysis of freely circulating tumor DNA (ctDNA) to assess MRD in patients with PML. Materials and methods. From January 2016 to January 2022, 34 previously untreated PML patients were included in the study;average age - 32;stage > I - in 60 %;extramediastinal lesions - in 14.7 %;bulky disease - in 73.5 % of patients. Positron emission tomography combined with computed tomography (PET-CT) was performed;ctDNA was determined to assess the completeness of remission. Results. Eighteen patients received treatment according to the PML-16 protocol (6 courses of chemotherapy;2 blocks of RmNHL-BFM-90 + 4 courses of R-EPOCH). After the end of therapy, all 18 patients achieved PET-negative remission. The next 16 patients received treatment according to the PML-19 protocol (4 courses of chemotherapy;2 blocks of R-mNHL-BFM-90 + 2 courses of R-EPOCH) in combination with lenalidomide. After the end of therapy, 9 (56 %) patients achieved PET-negative remission;7 (44 %) retained pathological activity (D4-5 points). After 3 and 6 months 15 (94 %) patients achieved normalization of metabolic activity. Considering the high frequency of false-positive results in patients with PML, a ctDNA study was performed to determine the depth of remission in 15 patients. After the end of therapy, all 15 patients had complete elimination of ctDNA. Of these, 5 (33 %) remained PET-positive at the end of treatment. During further observation, after 3-6 months, in 4 patients the level of metabolic activity decreased to physiological without the use of consolidating therapy. After the end of therapy, one patient suffered the new coronavirus infection, COVID-19. A month later, residual formation of SUVmax 14.2 remained in the mediastinum. The patient is currently under observation. With a median follow-up of 36 months (9 to 76 months) all 34 patients are in remission. Conclusion. The effectiveness of PML-16 made it possible to abandon the consolidation therapy and refuted the idea of the need for 6 courses of CT. The combination of programs based on the application of the principle of high-dose short-pulse induction of remission (R-mNHL-BFM-90) in combination with the prolonged administration of medium doses (R-EPOCH) was crucial in achieving a successful result. The inclusion of lenalidomide in the "PML-19" program made it possible to achieve complete remission in 100 % of cases after 4 courses. The possibility of using DNA analysis to assess MRD in patients with PML was shown.Copyright © 2022 Izdatel'stvo Meditsina. All rights reserved.