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Our charity's mission is dedicated to beating blood cancer by funding research and supporting those affected. Since 1960, we have invested over 500 million in blood cancer research, transforming treatments and saving lives. Since 2015 there has been a Support Services team within the charity. This service was established to provide information that the blood cancer community can trust, in a language they can understand. By connecting and listening to our community they deepen our understanding and help shape our work. Research suggests that blood cancer patients are more likely than any other patients to leave their diagnosis appointment feeling they do not fully understand their condition. Our service can often consolidate the information given by clinicians. Patients also need advice and support on how to adapt to day-to- day life after their diagnosis. There are challenges that are unique to blood cancer, such as living with cancer as a chronic condition, being on 'watch and wait' or fluctuating remissions and relapses. In 2023 the Support Services team have a 7 day presence on our phone line, email and social media platform where people can communicate with one of our trained blood cancer support officers, or one of three Registered Nurses, all who can provide information about blood cancer diagnosis and help with emotional and practical support. We also run an online community forum where people affected by blood cancer can connect, share experiences and provide peer support. The highly experienced haematology nurses provide a clinical aspect to the support of the Blood Cancer Community that enhances the established patient centred support given historically by the charity. The nurses advanced knowledge and experience of haematological cancers, treatments, side effects, holistic care and NHS process can further guide the community. This is in addition to the invaluable information from their treatment teams. In 2023 the Support Services team are now reaching thousands of the blood cancer community. We understand that in the past 3 years the COVID-19 pandemic and the work of our charity around this will have influenced the significant increase in contacts but equally the robust and trusted services provided through this charity has contributed too.
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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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Introduction: Croatian National Cancer Registry of Croatian Institute for Public Health reported that in year 2020 lung cancer was the second most common cancer site diagnosed in men with 16% and the third most common in women with 10% incidence among all cancer sites. Unfortunatelly lung cancer has the highest mortality in both men and women. Haematological malignancies had 7% share in all malignancies in both male and female cances cases. In 2020 190 newly diagnosed cases of lymphatic leukemia in men and 128 cases in women were reporeted, meaning 1.5 and 1.2% of all malignancies, respectively. Chronic lymphatic leukemia (CLL) is an advanced age disease and incidence increases with age. Impaired immunity, T and B cell dysfunction in CLL, chromosomal aberations, long-term immunosuppressive therapy and genetic factors can all cause secondary malignancies. Co- occurence of solid tumors and CLL is very rare. Although patiens with CLL have an increased risk of developing second primary malignancies including lung carcinoma, the data about their clinical outcomes are lacking. Parekh et al. retrospectively analyzed patients with simultaneous CLL and lung carcinoma over a 20-year period, and they found that ~2% of patients with CLL actually developed lung carcinoma. The authors claimed that up to 38% of patients will also develop a third neoplasm more likely of the skin (melanoma and basal cell carcinoma), larynx (laryngeal carcinoma) or colon. Currently there are no specific guidelines for concurrent CLL and non-small cell lung carcinoma (NSCLC) treatment. Usually, when the tumors are diagnosed simultaneously, treatment is based to target the most aggressive malignancy, as the clinical outcomes depend on the response of the tumor with the poorest prognosis. For this reason, a multidisciplinary approach is mandatory. Case report: A patient with history of coronary heart disease, myocardial infarction and paroxysmal atrial fibrillation was diagnosed in 2019 (at the age of 71) with B chronic lymphocytic leukemia with bulky tumor (inguinal lymph nodes 8x5 cm), stage B according to Binet, intermediate risk. He was treated with 6 cycles of chemoimmunotherapy (rituximab/cyclofosfamid/fludarabine). In 10/2019 remission was confirmed, but MSCT described tumor in the posterior segment of upper right lung lobe measuring 20x17 mm and bilateral metastases up to 11 mm. Bronchoscopy and biopsy were performed, and EGFR neg, ALK neg, ROS 1 neg, PD-L1>50% adenocarcinoma was confirmed. He was referred to Clinical Hospital Center Osijek where monotherapy with pembrolizumab in a standard dose of 200 mg intravenously was started in 01/2020. Partial remission was confirmed in October 2020. Immunotherapy was discontinued due to development of pneumonitis, dysphagia and severe weight loss (20kg), but without radiologically confirmed disease progression. At that time he was referred to our hospital for further treatment. Gastroscopy has shown erosive gastritis with active duodenal ulcus, Forrest III. Supportive therapy and proton pump inhibitor were introduced. After complete regression of pneumonitis, improvement of general condition and resolution of dysphagia, no signs of lung cancer progression were found and pembrolizumab was reintroduced in 12/2021. Hypothyroidism was diagnosed in 01/2021 and levothyroxine replacement ther apy was started. In 03/2021 he underwent surgical removal of basal cell carcinoma of skin on the right temporal region with lobe reconstruction. From 02/2021, when pembrolizumab was reintroduced, regression in tumor size was continously confirmed with complete recovery of general condition. He was hospitalized for COVID 19 infection in 09/2021, and due to complications pembrolizumab was discontinued till 11/2021. Lung cancer immunotherapy proceeded till 11/2022, when Multidisciplinary team decided to finish pembrolizumab because of CLL relapse. CLL was in remission till August 2022 when due to B symptoms, lymphcytosis, anemia and generalized lymphadenopathy, hematological workup including biopsy of cervical lymph node was performed and CLL/SLL relapse was confirmed. Initially chlorambucil was introduced, but disease was refractory. Based on cytogenetic test results (IGHV unmutated, negative TP53) and due to cardiovascular comorbidity (contraindication for BTK inhibitors) venetoclax and rituximab were started in 01/2023. After just 1 cycle of treatment normal blood count as well as regression of B symptoms and peripheral lymphadenopathy occured, indicating the probability of complete disease remission. In our patient with metastatic lung adenocarcinoma excellent disease control is achieved during 41 month of treatment in first line setting. Furthermore, relapsed/refractory CLL/SLL is currently in confirmed remission. Conclusion(s): Successful treatment of patients with multiple primary malignancies is based on multidisciplinarity, early recognition and management of side effects, treatment of comorbidities with the aim of prolonging life, controlling symptoms of disease and preserving quality of life.
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Background & Aim: Gene therapies has become recognized for its remarkable clinical benefits in a variety of medical applications, in particular recent approval of an Ad vector-based COVID-19 vaccines have attracted recent global attention. Here, we present key considerations for GMP compliant process development for Coxsackie virus type B3 (CVB3), an oncolytic virus designed for clinical trial in triple-negative breast cancer. Methods, Results & Conclusion(s): CVB3 is a non-enveloped, linear single-strand RNA virus with a size of approximately 27-33 um in diameter. From the initial type using the zonal rotor centrifuge to the advanced type using the tangential flow filtration system and ion chromatograph, we considered the points of the design concept in constructing the manufacturing process. The final design system is constructed as a closed and single-use manufacturing system in which all processes from upstream large-scale cell culture to downstream target purification and concentration steps. In brief, HEK293 cell suspension extended in 3L serum-free medium infected with CVB3, up to 3.6 times 10 to 7 of TCID50 /mL before going to downstream steps, made total 150 mL of final products as 8.43 times 10 to 7 of TCID50/mL concentration. Although further quality control challenges remain that is removal of product-related impurities such as human cellular proteins and residual DNA/RNA to increase virus purity, this concept is effectively applicable even for other types of viruses as GMP manufacturing processes, and would be also important for technology transfer to future commercial production.Copyright © 2023 International Society for Cell & Gene Therapy
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Introduction: Surgical treatment of rectal cancer depends on clinical stage, size and location of primary tumor. A sphincter preserving technique such as low anterior resection (LAR) is the preferred method if negative distal margin can be achieved. If an adequate distal margin cannot be obtained, an abdominoperineal resection (APR) is required. A proctosigmoidectomy (Hartmann's procedure) is performed in patients with potentially curable obstructing rectal cancer after neoadjuvant chemoradiotherapy, or as a palliative treatment for locally advanced rectal cancer. Aim(s): The aim of this retrospective study was to investigate the impact of COVID 19 pandemic on the number and type of surgeries performed for the treatment of rectal cancer in UHC Zagreb, Department of Surgery. Material(s) and Method(s): Collected data were extracted from medical records of the patients who underwent surgery at the Department of Surgery from 1st of January 2016 to 31st of December 2022 with prior Ethics Committee approval. Total of 688 patients were included. Retrospective analysis of number and type of surgery was done consecutively by years for the period of interest. Result(s): In 2016 total of 75 patients underwent elective surgery for rectal cancer. LAR was performed in 64% (N=48) of patients, Hartmann's procedure in 20% (N=15), and APR in 16% (N=12). In 2017, 94 surgeries were performed. LAR accounted for 64% (N=60), Hartmann's procedure 17% (N=16), and APR 19% (N=18). In 2018, 115 surgeries were performed. LAR accounted for 69% (N=79), Hartmann's procedure 10% (N=12), and APR 21% (N=24). In 2019, 80 surgeries were performed. LAR accounted for 67% (N=54), Hartmann's procedure 9% (N=80), and APR 24%. In 2020, 78 surgeries were performed. LAR accounted for 59% (N=46), Hartmann's procedure 14% (N=11), and APR 27% (N=21). In 2021, 124 surgeries were performed. LAR accounted for 66% (N=82), Hartmann's procedure 14% (N=17), and APR 20% (N=25). In 2022, 122 surgeries were performed. LAR accounted for 64% (N=78), Hartmann's procedure 15% (N=18), and APR 21% (N=26). Conclusion(s): Our results show steady growth in numbers of performed surgeries in the years prior to the pandemic, with exception of the year 2019 when our department underwent organizational changes. In 2020, significant decrease in number of surgeries was observed as a result of restrictive epidemiological measures established to reduce the spread of COVID 19 infection. COVID 19 pandemic measures also resulted in delayed diagnosis and treatment of rectal cancer which is indirectly shown through the increasing share of Hartmann's procedure. In the years following the relaxation of measures, significant increase in number of performed surgeries that exceeded all the pre-pandemic years was recorded. Constant elevated share of Hartmann's procedure was noted as possible consequence of post COVID delay in diagnosis and confirmation of rectal cancer in more advanced stages of disease.
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Background: The COVID-19 pandemic impacted the delivery of cancer care and outcomes in the United States (US). We examined the association between time-varying state-level weekly COVID19 mortality and progression-free survival (rwPFS), time to progression (rwTTP), and survival (rwOS) among pts with advanced non-small cell lung cancer (advNSCLC). Method(s): This retrospective study used the nationwide Flatiron Health electronic health recordderived de-identified database. The cohort included community oncology pts diagnosed with advNSCLC between March 1, 2020 and December 31, 2021 (follow-up through March 30, 2022). We extracted US data on COVID-19 deaths from the COVID-19 Data Repository by the Center for Systems Science and Engineering at Johns Hopkins University. We calculated state-level weekly COVID-19 death rates as weekly COVID-19 deaths per state population size from the 2019 American Community Survey. We categorized rates into quintiles based on all weekly rates during the observation period. Analyses were restricted to treated pts and indexed to start of first-line therapy. For rwPFS analyses, first occurrence of progression or death was considered an event, and pts were censored at last clinic note date. For rwTTP, only progression (not death) was considered an event, and pts with no event were censored at last clinic note date. For rwOS analyses, pts who did not die were censored at last structured activity. We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between weekly time-varying state-level COVID-19 mortality rates and outcomes of rwPFS, rwTTP, and rwOS, adjusted for age at diagnosis, race/ethnicity, and state. Result(s): Among 7,813 advNSCLC pts, the median age at diagnosis was 70 years, the majority of the cohort was non-Hispanic White (59%), had non-squamous cell histology (68%) and a history of smoking (87%). Compared to pts living in states with the lowest quintile of COVID-19 mortality rates (Q1), pts living in states with the highest COVID-19 mortality (Q5) had worse rwOS (Q5 vs. Q1: HR 1.46, 95% CI 1.26-1.69) and rwPFS (Q5 vs. Q1: HR 1.18, 95% CI 1.05-1.33). No association was observed with rwTTP (Q5 vs. Q1: HR 1.05, 95% CI 0.90-1.22). Conclusion(s): In this study of real-world oncology data, we demonstrated the use of publicly-available COVID-19 mortality data to measure the time-varying impact of COVID-19 severity on outcomes in pts with advNSCLC. Higher state-level COVID-19 mortality rates were associated with worse rwOS and rwPFS among advNSCLC pts. The association with increased mortality among pts with advNSCLC may be related to COVID-19-related mortality or other factors such as pre-existing comorbidities which were not explored in this study.
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Project objective: Despite the recent revolution in immune checkpoint inhibitors (ICIs), only modest improvement in overall survival and likely caused by not enough potent cellular immunity among BC patients. Our lab has been focus on inducing cellular immunity against HER2+ BC through vaccination against the tumor-associated antigen HER2. Approximately 20 years ago, we performed an experimental pilot study by administrating HER2 peptide and recombinant protein pulsed dendritic cells (DC vaccine) to six patients with refractory HER2+ advanced or metastatic (stage II (>= 6 +LN), III, or stage IV) BC. We followed the patients on 2019 found that all of the six patients were still alive, 18 years after vaccination. Their blood sample were analyzed with cytometry by time-offlight (CyTOF) and found there is a significantly increased presence of CD27 expressing memory T cells in response to HER2 peptide stimulation. Recent report on the SARS-CoV2 mRNA vaccine also suggested that CD27 expressing memory T cells plays a critical role in long-lasting cellular immunity against SARS-CoV2 infection. Therefore, we hypothesized that CD27 plays a critical role in cellular immunity against BC, and the stimulation of CD27 expressing T cells with mAb targeting CD27 significantly increase the cellular immunity triggered by vaccination against tumor-associated antigen. Result(s): We recapitulate the rise of CD27+ antigen specific T cells among the vaccinated patients using a transgenic mouse model expressing human CD27. When combined the adenoviral-vector based HER2 (Ad-HER2) vaccination with a single dose of human aCD27 antibody (Varlilumab), we found there is a robust increase in the HER2 specific T cells compared to vaccination alone, especially CD27+CD44+ memory CD4 T cells, even after 120 days post vaccination. Using an ICIinsensitive syngeneic HER2+ BC models, we found 50% of mice in the combination group of aCD27 antibody plus Ad-HER2 showed total tumor regression by the end of study. When combined with anti-PD1 antibody, the combination of AdHER2 and Varlilumab leads to total tumor regression in 90% of tumor bearing mice with syngeneic HER2+ BC, indicating that the vaccination against tumor associated antigen HER2 plus anti-CD27 antibody sensitized ICI-insensitive HER2+ BC toward ICI. Conclusion(s): Our data demonstrates that the administration of anti-CD27 antibody significantly increase the long term presence of CD27+ antigen specific memory T cells after vaccination against tumor associated antigen HER2. As consequence, combination of anti-CD27 with HER2 sensitized the immune unresponsive breast cancer toward anti-PD1 antibody. Our study suggests that the vaccination against tumor-associated antigen with mAb targeting CD27 leads to the robust cellular immunity, which is required for successful ICIs against breast cancer.
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BACKGROUND: Older patients with cancer are at risk of physical decline and impaired quality of life during oncological treatment. Exercise training has the potential to reduce these challenges. The study aim was to investigate the feasibility and effect of a multimodal exercise intervention in older patients with advanced cancer (stages III/IV). PATIENTS AND METHODS: Eighty-four older adults (≥65 years) with advanced pancreatic, biliary tract, or non-small cell lung cancer who received systemic oncological treatment were randomized 1:1 to an intervention group or a control group. The intervention was a 12-week multimodal exercise-based program including supervised exercise twice weekly followed by a protein supplement, a home-based walking program, and nurse-led support and counseling. The primary endpoint was change in physical function (30-second chair stand test) at 13 weeks. RESULTS: Median age of the participants was 72 years (interquartile range [IQR] 68-75). Median adherence to the exercise sessions was 69% (IQR 21-88) and 75% (IQR 33-100) for the walking program. At 13 weeks, there was a significant difference in change scores of 2.4 repetitions in the chair stand test, favoring the intervention group (p < .0001). Furthermore, significant beneficial effects were seen for physical endurance (6-minute walk test), hand grip strength, physical activity, symptom burden, symptoms of depression and anxiety, global health status (quality of life), and lean body mass. No effects were seen for dose intensity, hospitalizations, or survival. CONCLUSION: A 12-week multimodal exercise intervention with targeted support proved effective in improving physical function in older patients with advanced cancer during oncological treatment.
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Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Aged , Exercise Therapy , Hand Strength , Humans , Lung Neoplasms/therapy , Quality of LifeABSTRACT
Background/Aims The use of Janus Kinase Inhibitors (JAKi) has been gradually increasing overtime in the management of rheumatoid arthritis (RA) and other inflammatory arthritis and these appeal to patients. being oral agents. Nevertheless, rheumatologists have become cautious about their use since recent trials have shown safety concerns about VTEs, MACE and malignancies. Methods We decided to study use of JAKi at our centre in Princess of Wales Hospital Bridgend. The aim was to assess whether appropriate patients were selected (considering cautions about MACE, VTEs and malignancies). We also wanted to see whether all patients had required pretreatment safety testing and post-treatment monitoring performed. Results These were 70 patients;59 were females and 11 were males. All of them were diagnosed as RA. Average age was 61.1 years (20-85), average duration of disease 129.9 months (16-340) and average duration of treatment was 58.1 weeks. The most common JAKi being used was baricitinib (84%) followed by tofacitinib (12%) and upadacitinib (4%). 50% patient were on concomitant csDMARDs among whom two-thirds were on methotrexate. Looking at previous biologic use, 9 patients were biologic naive, 22 had one biologic, 15 had two biologics used in the past. All patients were appropriately selected (severe RA and no significant risk factors for MACE, VTEs and malignancies). All patients had pre-treatment Hepatitis B, Hepatitis C, latent TB, FBC and LFTs checked. All patients had FBC and LFTs monitored post treatment. No patient developed VTE, MACE or cancer on treatment. 84.2% patients had lipids tested before starting JAKi. 22.8% patients had abnormal lipids before Rx initiation and 62.5% of these were on lipid lowering Rx. All patients had lipids tested post treatment, but the timing was quite variable and only 62.5% of patients had lipids tested on the recommended time. There were 2 deaths recorded in this cohort. One of those was an 80-year-old RA patient on baricitinib 2mg OD, who died due to chest infection on the background of ILD. He was not on steroids or csDMARDs. The second patient was 63 years' old (on baricitinib 4mg OD), and died due to respiratory sepsis, and was also on azathioprine. She had RA with advanced ILD. The reasons for discontinuing JAKi were inefficacy (46%), side effects (39%) and both inefficacy and side effects (15%). 41.4%of patient experienced side effects due to JAKi. These included infection 28%, deranged lipids 17%, cytopenia 14%, deranged LFTs 14%, GI side effects 10%, skin rash 7% and varicella zoster 3%. Conclusion There has been steady increase in the use of tsDMARDs for RA and other rheumatic conditions. Due to short half-life, these drugs became a popular choice during COVID-19 pandemic but on the other hand safety monitoring became extremely challenging during this time.
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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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PURPOSE/HYPOTHESIS: Poor physical performance and negative mood are two risk factors for functional decline among older adults with lung cancer. Yet, targeted interventions to maintain independence prevent functional decline are not well studied. Our primary objective was to assess the feasibility of a novel virtual health physical therapy (PT) plus progressive muscle relaxation (PMR) intervention with longitudinal microbiome biospecimen collection delivered to older adults with advanced lung cancer. Secondary objectives were to characterize functional status and clinical factors pre and post-study intervention. NUMBER OF SUBJECTS: We accrued adults aged >=60 years with advanced non-small cell or extensive-stage small cell lung cancer receiving treatment at The Ohio State University James Comprehensive Cancer Center (OSU-JCCC) in the Thoracic Oncology department (N=22). There were no exclusion criteria pertaining to Eastern Cooperative Oncology Group (ECOG) performance status, laboratory values, prior cancer diagnoses, presence of comorbidities, or brain metastases. MATERIALS AND METHODS: Participants were asked about functional status, symptoms, mood through the PHQ-9, GAD-7, POMS, and acceptability questions about the program. PT evaluation and assessment included SPPB and 2- or 6-minute walk test outcomes. The study sought to collect gut microbiome samples for every in-person visit and activity monitoring data (Actigraph) on a subset. Feasibility was defined as successfully collecting specimens, wearing an Actigraph activity monitor, and adhering to the intervention. PT and psychologists evaluated participants in-person at the first and final visit. The rest of the 12-week intervention was conducted via virtual health. Physical therapy intervention consisted of endurance, strength, and flexibility exercises. RESULT(S): In total, 22 patients consented and 18 started the intervention (81.8%). Seven microbiome samples were collected from four participants. Six patients collected activity monitoring data. Among the 18 participants, 11 participants (61.1%) completed 70% or more of all the intervention visits. The SPPB data show a moderate effect size (Cohen's d=0.24) from pre- to post-data. On average patients improved by 1.8 total points on the SPPB. Patients demonstrated improvement on timed walk tests throughout intervention from an average of 108 feet pre-intervention to an average of 138.4 feet post intervention. CONCLUSION(S): Despite the challenges of the COVID-19 pandemic, longitudinal biospecimen and correlative data collection were feasible in the context of PT and PMR intervention among older adults with advanced lung cancer. Virtual physical therapy interventions can be safely delivered to improve physical performance as demonstrated by a moderate effect size for the SPPB in this patient population. CLINICAL RELEVANCE: Based on the feasibility study results, delivering a virtual PT intervention to older patients with lung cancer can improve SPPB score leading to decreased frailty and improve quality of life among patients.
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Introduction: Colorectal cancer (CRC) screening is a critical preventative service and part of routine patient care. CRC is the second leading cause of cancer death in the US, and yet a third of the eligible population does not undergo routine screening. Endoscopy centers have been stretched thin by both COVID-19 and the recent drop in screening initiation age to 45. Fecal immunochemical testing (FIT), a sensitive and specific CRC screening modality, may be used to reach and risk-stratify more patients to increase the yield for detecting advanced neoplasia and cancer, reducing pressure on colonoscopy centers. Unfortunately, FIT is often suboptimal as patients inconsistently complete and return the test for analysis. Method(s): We performed a retrospective analysis of 5211 individuals at a single internal medicine clinic who had FIT ordered as part of USPSTF recommended care from 01/2017 through 12/2021. Starting in 01/2021 we instituted a dedicated patient navigator to support patients in completing FIT. Chi-square, Fisher exact test, and Student's t-tests were performed for descriptive analyses. Multivariable logistic regression was used to compare FIT kit drop off rates pre- and post-intervention, with the model adjusted by age, gender, race, ethnicity, language, and insurance status. Analysis was performed in SAS version 9.4. (Table) Results: The post-intervention period included 1181 (22.7%) patients. The predominant reasons cited for failure to complete testing were forgot (25%), too busy (13%), and lost kit (11%). Our intervention improved drop off rates from 46.4% to 51.3% at 2 weeks (OR 1.19, 95%CI 1.01-1.41), 56.7% to 73.7% at 1 month (2.14 [1.78-2.58]), 64.7% to 89.7% at 3 months (4.73 [3.66-6.12]), and 78.9% to 98.2% at 1 year (14.39 [8.25-25.12]). Overall, our intervention improved FIT kit drop off rates by 53.4% (1.53 [1.30-1.81]). FIT was positive in 4.9% (p=0.0529). (Figure) Conclusion(s): FIT can increase CRC screening rates, particularly in resource-limited settings, and may decrease the burden on endoscopy centers nationwide by improving the efficiency of colonoscopy in the average risk screening population. The addition of a dedicated patient navigator is a simple intervention that, by providing culturally competent care and personalized attention, improves completion rates and return time, allowing FIT to be a reliable method of screening. The ability to increase screening rates and prioritize patients for diagnostic colonoscopies will ultimately lead to earlier detection and treatment of CRC.
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The proceedings contain 35 papers. The topics discussed include: germline variants and prognostic factors for cutaneous melanoma in children and adolescents;association between polygenic risk score and multiple primary melanoma;Porocarcinoma: an epidemiological, clinical, and dermoscopic 20-year study;primary cutaneous melanoma and COVID-19: a hospital-based study;atypical spitz tumors: an epidemiological, clinical and dermoscopic multicenter study with 16 years of follow-up;pediatric melanoma: an epidemiological, clinical and dermoscopic multicenter study;recurrence-free survival prediction in melanoma patients by exploiting artificial intelligence techniques on melanoma whole slide images;ultra-high frequency ultrasound and machine learning approaches for the differential diagnosis of melanocytic lesions;and genetic determinants of response to therapy in a real-world setting of advanced/metastatic melanoma patients: whole-exome sequencing and CFDNA analysis.
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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.
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Background: The National HIV Mortality Review (NHMR) was launched by UK Health Security Agency (UKHSA) and British HIV Association to better recognise causes of death and preventable death, and to describe end-of-life care, among people with HIV. Method(s): UK HIV services submitted data on all known deaths among people with HIV under their care in 2021 through a secure online form. Cause of death was categorised by an epidemiologist and four clinicians using the Coding Causes of Death in HIV protocol. Result(s): In 2021, 101 services reported 606 deaths among people with HIV to NHMR. In 2019, 74 services reported to the NHMR while 121 reported in 2020. Median age at death was 58 [interquartile range (IQR): 56-59] and most (76%) were male. Death cause was ascertainable for 78% (n=475), with the most common being non-AIDS-related cancers (26%), followed by non-AIDS-defining infections (19%), cardiovascular disease (16%), AIDS (9%), substance misuse (8%), respiratory disease (4%), accident/suicide (3%), liver disease (2%) and other causes (11%). COVID- 19 caused or contributed to 11% of all deaths. Thirtythree people (5%) died within a year of HIV diagnosis, 90% of these were diagnosed late (CD4<350 cells/mm3), 80% very late (CD4<200 cells/mm3), 54% diagnosed with AIDS and 33% had documented missed opportunities for earlier diagnosis. Viral suppression (<200 copies/mL) (87%) and treatment coverage (98%) was high with the median time on treatment 13 years [IQR: 8-20]. Common lifestyle risk factors in the preceding year included smoking (33%;n=179), excessive alcohol use (20%;n=103). Other factors included drug use (non-injecting and injecting) and opioid substitution therapy. Death had been expected for 298 (49%) individuals, of whom 230 had discussed end-of-life care and 108 had a documented advanced end-of-life care plan in place. Conclusion(s): Over half of people living with diagnosed HIV are aged over 50. Most deaths were not AIDS related however, one in eleven people with diagnosed HIV in the UK died from AIDS. Of people that died within a year of diagnosis, one in three had documented missed opportunities for earlier HIV diagnosis.
ABSTRACT
Introduction: Hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS), is a clinical syndrome characterized by hepatomegaly, right-upper quadrant pain, and ascites that occurs most commonly in the setting of high-dose chemotherapy or hematopoietic stem cell transplantation (HSCT). The diagnosis can be confirmed on biopsy. Cemiplimab is an immune checkpoint inhibitor recently approved for the treatment of cutaneous squamous cell carcinoma. There are currently no known reports of immune checkpoint inhibitor-related VOD/SOS. Case Description/Methods: A 58-year-old female with a history of locally advanced basal cell carcinoma of the left eye treated with six months of Cemipilimab presented with ascites. On admission, labs were notable for a total bilirubin of 1.2, mildly elevated liver function tests, alkaline phosphatase 884, and international normalized ratio 2.1. A diagnostic tap revealed a high SAAG ascites that was negative for infection. A comprehensive serological workup for viral, metabolic and autoimmune causes was unrevealing. A transjugular liver biopsy demonstrated a hepatic venous pressure gradient of 18mmHg, nodular regenerative hyperplasia (NRH), and portal venopathy. The patient was discharged on steroids but returned one month later for recurrent ascites and worsening bilirubin to 12.6 (direct 7.3);COVID PCR was negative. A full rheumatologic and vasculitis workup was unremarkable. Repeat biopsy (Figure 1) demonstrated moderate NRH changes, prominent central vein sclerosis with fibrous obliteration, signs of SOS/ VOD and central venulitis with fibrotic changes with sinusoidal portal hypertension. Discussion(s): VOD occurs most often with hematopoietic stem cell transplantation, and chemotherapeutic agents. Here we present the first case of checkpoint inhibitor-induced VOD/SOS. Despite discontinuation of the offending agent and a trial of steroids, the patient's clinical course continued to deteriorate. She eventually developed refractory ascites and portosystemic encephalopathy. She was deemed not a candidate for liver transplant given her underlying malignancy. She was transitioned to home hospice before further treatment, such as Defibrotide could have been pursued. VOD associated with immune checkpoint inhibition should be considered in the differential of patients who develop new onset liver dysfunction and ascites while receiving these medications (Figure Presented).
ABSTRACT
Introduction: Colorectal cancer (CRC) is the third most prevalent cancer in the United States, with a 4% lifetime incidence. While more clinicians have begun ordering multitarget stool DNA (mt-sDNA) testing due to the COVID-19 pandemic, adherence to guidelines on mt-sDNA and rates of subsequent follow-up testing has not been well studied. We assessed the appropriateness of mt-sDNA orders and rate of high-quality colonoscopy completion following a positive result in a large academic medical center. Method(s): We identified patients ordered for mt-sDNA in primary care and gastroenterology clinics at our institution between April 2020 and July 2021. For each case, we reviewed the appropriateness of mtsDNA testing, documentation of shared decision making, result of testing, and subsequent follow-up. Appropriateness was defined in accordance to the most recent American College of Gastroenterology guidelines on mt-sDNA use for CRC screening. Result(s): Of the 797 patients in our study, 685 (86%) met all appropriateness criteria for mt-sDNA testing (Table). Shared decision making was documented in 488 (62%) cases, and the most common reason for ordering mt-SDNA was hesitancy for colonoscopy. 483 patients (61%) completed mt-sDNA testing, of which 74 cases (15%) were positive. Rates of positivity were higher in cases of inappropriate (28%) rather than appropriate (13.7%) orders (p = 0.01). Colonoscopy was ordered in 73 cases (99%) and completed by 59 patients (80%). Of the 56 patients who underwent colonoscopy at our institution, most had documentation of a high-quality colonoscopy, defined as adequate prep (84%), cecal intubation (93%), visualization of the appendiceal orifice and ileocecal valve (94%), and right colon retroflexion (83%). Sixteen patients (29%) were found with advanced adenomas and 19 (34%) had other adenomas or sessile polyps. Among the 409 patients with negative tests, a 3-year follow-up recommendation was documented for 369 patients (90%). Conclusion(s): Most clinicians at our institution identified appropriate patients for mt-sDNA testing and provided appropriate follow-up< and the majority of patients who underwent colonoscopy had documentation of a high-quality colonoscopy. In contrast, there were suboptimal rates of mt-sDNA completion and documentation of shared decision making. Further studies are needed to identify barriers to documentation of shared-decision making and to completion of high-quality colonoscopies in patients being screened with mt-sDNA.
ABSTRACT
Introduction: Achalasia is a motility disorder of the esophagus characterized by impaired relaxation of the lower esophageal sphincter and loss of peristalsis in the distal esophagus. It is a rare condition with an annual incidence of 0.5-1.2 per 100,000 individuals. The etiology of primary achalasia is unknown, however secondary achalasia can be attributed to malignancy, infections or systemic diseases such as amyloidosis. An infrequent complication of achalasia is esophageal squamous cell carcinoma which has a prevalence of 26 in every 1,000 cases. We present a case of interval locoregionally advanced esophageal squamous cell carcinoma only 2 years after a normal upper endoscopy. Case Description/Methods: A 67-year-old female with known achalasia and previous pneumatic dilation in her 30s presented to our outpatient clinic in 2019 with complaints of worsening chronic dysphagia. EGD was performed which revealed a significantly dilated esophagus with candida esophagitis. Despite completing antifungal therapy, she continued to experience dysphagia to solids and liquids. Barium swallow demonstrated absent peristalsis with pooling of contrast within the esophagus. High-Resolution Manometry testing demonstrated absent peristalsis. She opted for surgical myotomy, however due to COVID restrictions, the procedure was delayed. Repeat EGD was performed in 2022 for pre-surgical evaluation and showed a large obstructing friable esophageal mass in the lower third of the esophagus. Pathology was consistent with invasive poorly differentiated squamous cell carcinoma. PET scan showed locoregional disease with FDG-avid esophageal and gastrohepatic node lesions. She was started on chemoradiation with Paclitaxel and Carboplatin (Figure). Discussion(s): The risk of esophageal squamous cell carcinoma in achalasia has significantly increased with incidence of approximately 1 in 300 patients. The presumed mechanism of malignancy in achalasia is poor emptying resulting in food stasis, bacterial overgrowth and inflammation leading to dysplasia and development of carcinoma. Given the relatively low incidence, there are currently no guidelines on routine endoscopic screening to assess for malignancy in patients with achalasia. Survival rates are poor as patients are often diagnosed at advanced stages. This case aims to illustrate the importance and need for interval screening in individuals with long standing achalasia to improve outcomes.
ABSTRACT
Objective. To comparatively assess the early toxicity of treatment, its tolerability, 1-, 2-, 3-year overall survival, and local regional control rates in a group of patients receiving a radical cycle of accelerated or conventional fractionation chemoradiotherapy. Subjects and methods. The paper presents the interim results of a prospective study that included 115 patients with locally advanced cancer of the oropharynx, tongue root, and larynx who received a radical cycle of conformal chemoradiotherapy using accelerated (the single focal dose (SFD) was 2.4 Gy for 25-26 fractions) or conventional (SFD was 2.0 Gy for 32-33 fractions) fractionation in the period from 2015 to 2020. Results. An analysis comparing the study group with the control one revealed no statistically significant differences in the level of early toxicity of treatment (p=0.41). Complete tumor reversal was achieved in 57 (86.3%) patients in the study group and in 39 (79.5%) in the comparison group (p=0.23). The 1-, 2-, and 3-year local regional control rates in the accelerated fractionation group was 78.3+/-5.3%;65.9+/-6.8%, and 54.5+/-9.2%, respectively. The 3-year overall survival rate was 80.4+/-7.4%. These rates did not differ statistically from those in the conventional radiotherapy group (p=0.12-0.82);53 (80.3%) patients in the study group and 37 (75.5%) in the standard fractionation group received a radiation cycle without a forced interval. The treatment interval in the patients of both groups reduced the 2-year local regional control rates by 30.2% compared to that in the continuous cycle group (p=0.02). Conclusion. Accelerated fractionation chemoradiotherapy (SFD was 2.4 Gy for 25-26 fractions, the daily focal dose was 60.0- 62.4 Gy) is a procedure comparable with conventional radiation in its direct efficiency and safety. During the COVID-19 pandemic, this regimen can be considered to be a mainstay for patients with locally advanced oropharyngeal cancer in order to preserve the previous volumes of specialized healthcare.Copyright © A.V. SEMENOV I.A. GULIDOV O.G. LEPILINA M.U. RADZHAPOVA F.E. SEVRYUKOV K.B. GORDON.
ABSTRACT
Background: Mortality in PWH has been markedly improved by antiretroviral therapy (ART) but there are few reports describing this in the ~5 million virally suppressed (VS) PWH in South Africa(SA). We describe cause of death(CoD) in adults admitted to hospital with suspected pneumonia in SA. Method(s): We enrolled patients from June 2019-October 2021 at four hospitals and then followed them up for >=1 year. Eligibility included: Age >18 years, >=2 signs/symptoms of pneumonia, < 48 hrs since admission. Medical records were reviewed. All had HIV status ascertained and sputum sent for Xpert Ultra and mycobacterial culture. In PWH CD4 count, viral load (VL) and urine lipoarabinomannan were assessed. For those who died, CoD were ed from medical charts and interview of family. We categorised deaths as early: while admitted or to < 30 days after discharge;or late: >=30 days after discharge. We report mortality and CoD in VSPWH (VL<=50 copies/ml), unsuppressed and HIV uninfected(HUI) adults. Result(s): Of 1999 adults, 54% were PWH;61.2% reported receiving ART of whom 43.1% were VS;55.5% were women. Overall median age of VS was 48 years (IQR: 40-55) at entry;34.3% had comorbidities: hypertension (70.1%, obesity 41.3%, diabetes 28.9%) . Only 11.3% were diagnosed with HIV in the past year, 35.0%, had prior TB. Median CD4 count of VS patients was 289 cells/ mm3 (IQR:133-490) and Hb, 12.5g/dL (IQR:10.5-14.0);53.0% had CRP >100mg/ dL and 69.6% had oxygen saturation < 93% on room air;14.8% had >=1 assay positive for TB;and 42.9% were SARS-CoV-2 positive. Overall 25.4% VSPWH died compared to 31.2% and 22.9% of unsuppressed and HUI, respectively;median ages at death were 49 (IQR:43-59), 38 (IQR: 32-47) and 62 (IQR: 53-69) years respectively. Overall median times to early and late death was 8 (IQR: 4-16) and 104 (IQR: 75-254) days, respectively. The leading CoD in VSPWH were: COVID-19 (22.9%), chronic lung disease(CLD) (17.1%),malignancy (12.9%),sepsis, (12.9%) and TB (8.7%);in HIV unsuppressed, CoD were: advanced HIV and opportunistic infections-(TB,PJP)(55.5%), sepsis(9.6%), COVID-19(8.6%);and in HUI: COVID- 19(43.0%), cardiovascular disease (9.0%), TB(9.0%), malignancy (8.5%). Conclusion(s): Mortality in VSPWH admitted with suspected pneumonia was higher than in HUI and occurred 12 years earlier. The challenge for clinicians is to screen for diseases that disproportionately affect VSPWH and to try to prevent recurrent lung infections thereby increasing their comorbidity-free years and reduce mortality gaps.