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1.
HemaSphere ; 6:1930-1931, 2022.
Article in English | EMBASE | ID: covidwho-2032125

ABSTRACT

Background: Bing-Neel syndrome (BNS) is a rare complication of lymphoplasmacytic lymphoma (LPL) comprising LPL infiltration in the central nervous system (CNS). Clinical and radiological features are diverse;the diagnosis is confirmed by cerebrospinal fluid (CSF) analysis using immunological and molecular techniques. Rarely, a tissue biopsy is required. The pattern of presentation including systemic involvement and CSF features inform treatment strategies, which include CNS-penetrating therapies. Aims: To evaluate the diagnostic characteristics of patients with BNS and their influence on therapy. Methods: Data from patients referred between 2011-2021 for management of BNS to our academic neurohaematology centre were retrospectively reviewed. Those with imaging features alone or where it was not possible to distinguish from high-grade transformation were excluded. Results: Thirty-five patients (22 male, 13 female) were identified. Median age at diagnosis of BNS was 65 years (range 48-85). All patients were symptomatic. In 12 patients (34%) BNS was the de novo presentation of the IgM-related disorder, of which 3 (25%) had no detectable bone marrow (BM) infiltration of LPL at diagnosis. Approximately half (17;49%) had previously received therapy for LPL;median time to BNS diagnosis in these was 49 months (range 3-125). At BNS diagnosis, BM involvement with LPL ranged from 0-95%. More than half (14/26;54%) had <10% infiltrate and almost a fifth (4/26) >60%. All patients had leptomeningeal involvement and 8 (23%) additionally had parenchymal CNS disease. The majority had kappa light-chain predominance: IgMκ (n=26), non-IgMκ (n=5), IgMλ (n=3), one unknown. The BNS diagnosis was made on CSF analysis (n=28;80%), leptomeningeal tissue biopsy (n=3;9%) where CSF was non-informative, or by expert opinion based on supportive clinical, radiological and non-definitive CSF features (n=4;11%). Of those with a diagnosis based on CSF studies, B-cell clonality was confirmed by flow cytometry (27/28;96%), MYD88L265P mutation (18/28;64%) and immunoglobulin gene rearrangement (12/28;43%). In 22 samples with a full dataset, median CSF white cell count was 25/ul (1-233), CSF protein 1.69g/l (0.35-6), CSF IgM 9.49mg/l (1.07-61.5). The majority were treated with intensive regimens (rituximab, methotrexate (MTX), cytarabine (ARA-C) + thiotepa/idarubicin;n=30) due to the presence of CNS disease bulk and clinical need, and less commonly ibrutinib (n=3), bendamustine-rituximab (BR, n=1);one patient had intrathecal therapy (MTX, ARA-C) at the height of the COVID pandemic. Of those who received 2 cycles of intensive chemotherapy, 3 had >4 cycles followed by BCNU/thiotepa autologous stem cell transplant;10 proceeded to 'consolidation' (indefinite) ibrutinib to limit intensive chemotherapy or tackle systemic disease. At a median follow up of 26 months (range 1-121), median survival was not reached;2-year overall survival was 91% (95% CI 74-97). Three patients died during treatment (1 invasive fungal infection post COVID-19 during ibrutinib consolidation post MTX/ARA-C based therapy) and 2 during MTX-ARA-C based therapy;7 patients relapsed or progressed and were treated with ibrutinib: 1 relapsed after ibrutinib use, 1 patient was intolerant of ibrutinib and switched to BR. Image: Summary/Conclusion: Our cohort confirms that BNS may present with leptomeningeal disease and/or parenchymal disease, de novo and without systemic disease. Overall outcomes are excellent with intensive regimens, consolidated with or followed by ibrutinib;however, there are treatment-related toxicities emphasising the need for a tailored approach.

2.
Journal of Thoracic Oncology ; 17(9):S508-S509, 2022.
Article in English | EMBASE | ID: covidwho-2031530

ABSTRACT

Introduction: Lung cancer symptoms and secondary effects of cancer treatments impact quality of life and induce patients to excessive rest and lack of physical activity resulting in severe deconditioning. Exercise has been shown to increase performance status, strength, endurance and reduce emotional issues in lung cancer patients. Despite these benefit this approach is a poorly utilized strategy and several barriers must be overcome due to limited data, lack of awareness of the benefits of exercise, and limited patient motivation. Several programs of adapted physical activity are developing to support lung cancer patients during oncological treatments, adopting a personalized approaches. Rowing programs have been reported in cancer survivors to reduce risk factors and the impact of treatments complications, particularly lymphedema in breast cancer survivors. A pioneering program of adapted physical activity was developed by a multidisciplinary team in collaboration with an association for the support of cancer patients (Sicilian Association for Oncological Support), using rowing in patients with active metastatic cancer, to evaluate feasibility, response of patients, and to increase awareness of the benefits of physical activity in the fight against lung cancer. Methods: The program was launched in December 2019 from the idea of a young world rowing champion, but the advent of the COVID-19 pandemic led to the postponement of this project, which was subsequently developed from March 2021 to July 2021. The team was composed by oncologists, sports medicine specialists, two coaches specialised in adapted physical activity programs and a cardiologist. The voluntary logistic assistance was warranted by the rowing society “Canottieri Peloro”, which effectively allowed the project to be carried out, providing patients with equipment, a specialised team doctor and a well-equipped gym. In this preliminary experience we managed to include a small number of patients to assess the feasibility/validity of this approach and improve patients’ needs and satisfaction. Results: Four patients affected by metastatic lung adenocarcinoma with EGFR mutations joined the project (1 M/3 F;median age was 59.5, range 47-68;ECOG PS: 1). All patients presented well-controlled and mild symptoms related to the disease (cough, dyspnea, bone or chest pain) and were receiving active oncological treatments (first line EGFR-TKI: 2 patients;second line EGFR-TKI and maintenance chemotherapy). After a baseline clinical, oncological and cardiological evaluation personalized training program was developed. Briefly, indoor training and individual rowing sessions have been administered to patients. All patients reported full adherence to the training, developing a growing motivation and interest in improving physical performance. We did not recorded any worsening of symptoms or problems related to cancer treatments. The full contact with water and nature and the peculiar backwards motion of rowing had a positive impact on patients, that enjoyed the experience, reducing their anxiety for the future. Conclusions: This preliminary experience, previous developed as a support activity for lung cancer patients, might pave the way for further exploration of the role of rowing in this setting and promote a pivotal project to better define specific programs for metastatic cancer patients to improve compliance and response to cancer treatments. Keywords: Lung cancer, Adapted physical activity, Rowing

3.
Journal of Thoracic Oncology ; 17(9):S466, 2022.
Article in English | EMBASE | ID: covidwho-2031527

ABSTRACT

Introduction: Osimertinib is a selective third-generation EGFR-TKI inhibitor with an inhibitory effect on the T790M mutation. Interstitial lung disease (ILD) occurred in 3.9% of the Osimertinib-treated patients (with 0.4% fatal cases). Methods: Case report of fatal ILD induced by Osimertinib in a patient with metastatic lung adenocarcinoma. Results: We present the case of an 81-year-old female patient diagnosed with stage IVB lung adenocarcinoma (May 2020) with pulmonary, adrenal, and brain metastasis. Genetic sequencing showed an exon 19 deletion. She started erlotinib until documentation of disease progression in January 2021. In this context, she performed a liquid biopsy with the detection of a T790M resistance mutation. She started Osimertinib in February 2021. Her past medical history showed diabetes and dyslipidemia. Two months after starting Osimertinib, she went to the emergency department (ER) with a one-week evolution with progressive dyspnea, cough, and fever. Upon admission to the ER, she was conscious and cooperative, with respiratory distress signs, normal blood pressure, and hypoxemia. She had decreased breath sounds, and coarse crackles were audible bilaterally. In the blood sampling, Haemoglobin was 7.7 mmol/L, creatinine 0.08 mmol/L, platelets 257000x10ˆ9/L, C-reactive protein 28.6 nmol/L, and NT-proBNP 98 pmol/L. Rt-PCR for sars-CoV-2 detection was negative. X-ray showed bilateral diffuse infiltrates. She started oxygen therapy via nasal cannula at 3l/min and IV antibiotics. ABG values were pH 7.44, pCO2 37 mmHg, pO2 69 mmHg, HCO3 26 mEq/L, sO2 94%. On reassessment after 3 hours, she presented worsening dyspnea and dizziness, with higher oxygen needs (venturi mask, 60%). Chest CT angiography showed extensive bilateral diffuse ground-glass densification with crazy-paving areas. It also showed no signs of pulmonary embolism. We admitted her to a level 2 ICU unit for surveillance. Due to suspected drug toxicity, she started Methylprednisolone pulses (1000mg/3days). Six hours after admission, due to hypoxemia worsening, non-invasive ventilation was started with the need to escalate oxygen therapy to 100% FiO2. At 24h, she showed clinical and blood analysis improvement. Nonetheless, she still needed 100% fiO2 to maintain >92% oxygen saturation. On the 4th day of hospitalization, she was hypotensive, prostrated, and with little reaction to painful stimulation. She started palliative treatment and died on the same day. Conclusions: ILD is a rare adverse effect of the treatment with Osimertinib, and fatal ILD is even rarer. The time from starting Osimertinib to this side effect is variable between patients. Awareness is necessary for a rapid diagnosis and early treatment. [Formula presented] Keywords: Osimertinib, Intersticial Lung Disease, Adverse effect

4.
Journal of Thoracic Oncology ; 17(9):S310, 2022.
Article in English | EMBASE | ID: covidwho-2031526

ABSTRACT

Introduction: Cancer healthcare has been affected by Coronavirus disease 2019 (COVID-19) pandemic, interfering the normal function of oncology units and increasing diagnostic delay. Nevertheless, the rising incidence of respiratory infections led to an increase in medical consultations and chest imaging explorations. The aim of the study was to assess whether the increase in medical evaluations in the context of the pandemic led to an increase in the detection of early-stage thoracic tumours. Methods: We performed a retrospective single-institution study, collecting data from patients diagnosed with thoracic tumours between March, 1, 2020 and December, 31, 2021. We analysed their demographic and clinical data, symptoms at diagnosis and those who were diagnosed due to SARS-CoV-2 infection. Results: A total of 378 patients were analysed. Main results are shown in Table-1. Only 5.3% of newly diagnosed thoracic tumours were related to a suspected or confirmed SARS-CoV-2 infection. However, these patients were not diagnosed at earlier stages (p = 0.414). When we evaluated symptoms at diagnosis, we found that asymptomatic patients presented in earlier stages (p <0.000, Figure-1), being the majority incidental findings during the follow-up of oncological and non-oncological pathologies. Regarding symptomatic patients, most presented as locally advanced or metastatic diseases and no changes have been observed in the pattern of presentation compared to studies prior to the pandemic. [Formula presented] Conclusions: COVID-19 pandemic did not seem to increase thoracic tumours diagnosis in our study. Lung cancer diagnosed in patients due to SARS-CoV-2 infection was not detected in earlier stages. Clinical presentation was similar to previous reported outside COVID-19 pandemic. Nevertheless, we find that asymptomatic patients diagnosed incidentally presented more frequently in localized stages in comparison with symptomatic patients. [Formula presented] Keywords: COVID19, Lung Cancer, Diagnosis

5.
Journal of Thoracic Oncology ; 17(9):S301-S302, 2022.
Article in English | EMBASE | ID: covidwho-2031520

ABSTRACT

Introduction: The COVID-19 pandemic presented many challenges to the delivery of healthcare, especially for those with lung disease.Our group recently reported that the rate of new lung cancer diagnoses declined by 35% during the first year of the COVID-19 pandemic (year 2020). The objective of the present study is to evaluate the changes in new lung cancer (LC) diagnoses during the 2 years of the pandemic compared to the pre-pandemic era, and its subsequent effect on survival of lung cancer patients. Methods: This is a retrospective chart review study including patients diagnosed with lung cancer between March 1st 2019 and February 28th 2022 at the Peter Brojde Lung Cancer Centre at the Jewish General Hospital, Montreal. We compared 3 cohorts: Cohort 1 (C1): March 1, 2019 to February 29, 2020 (pre-COVID). Cohort 2 (C2): March 1, 2020 to February 28, 2021 (1st year of COVID). Cohort 3 (C3): March 1, 2021 to February 28, 2022 (2nd year of COVID;reporting for 11 months). Results: A total of 404 patients were diagnosed with lung cancer throughout the three-year study: 130 in C1, 103 in C2 and 171 in C3. Using C1 as a baseline, we found that new diagnoses of LC declined by 21% in C2, and rose by 32% in C3. The incidence of metastatic lung cancer increased by 41% in 2021 compared to 2019 (96 cases vs 68 cases) and by 63% compared to 2020 (96 cases vs 59 cases). Of the 59 metastatic LC patients diagnosed in 2020, 31 (52%) died, whereas 28/68 (41%) died in 2019. The median survival for metastatic LC in the first year of the pandemic decreased compared to pre-COVID year (14.5 vs 8.7 months) (Table 1). Statistical significance has not been reached as follow-up time was not long enough for year 2020 (p=0.58). Conclusions: The present study represents interim data of our ongoing effort to evaluate the effect of the COVID-19 pandemic on our lung cancer patients. The pandemic has led to a significant decline in LC diagnoses in the first year, and a subsequent increase in diagnoses during the 2nd year. Unfortunately, these changes resulted in a trend towards decreased survival for our metastatic LC patients. The final survival analysis will require longer follow-ups and this data will be presented at the meeting. [Formula presented] Keywords: COVID-19, Retrospective, Survival

6.
Journal of Thoracic Oncology ; 17(9):S213-S214, 2022.
Article in English | EMBASE | ID: covidwho-2031514

ABSTRACT

Introduction: It was aimed to evaluate the efficacy, local control and survival in patients with inoperable primary or metastatic lung cancer who underwent stereotactic body radiotherapy (SBRT) using the Cyberknife-M6 (CK-M6) with lung optimized treatment (LOT) module. Methods: Ethics committee (no: 2018-7/6) and scientific research project (OUAP (T) 2019/1) approval were obtained. 23 lesions of 21 patients were treated between April 2019 to December 2020 at our department. The patients were immobilized in the supine position by wearing a Synchrony vest, with the hands at their sides. A planning 4D-CT was obtained in a free breathing modality. The gross target volumes was created both on the full-inhale and full-exhale phases and internal target volume (ITV) was created. By taking an image of patients on the treatment device, tracking modality was selected according to the visibility of the target. Zero-View tracking was applied in 10 patients, 1-View in 10 patients, 2-View in 1 patients. 3 to 5 mm margin added for planning target volume (PTV) according to tracking method. Median ITV and PTV was 9,38 (2-52,34) and 20,27 (9,25-82,7) cc, respectively. An InCise2 multileaf collimator optimized by the Monte Carlo algoritm was used in all patients. A pair of the orthogonal kV X-ray imaging systems were used for simultaneous target tracking. Median prescribed dose was 48 Gy in 4 fractions (30-54 Gy in 3-6 fractions) administered consecutively or every other day. Prescription isodose covering 95% of PTV was 82,5% (77,4-99,3). Median conformity and homogeneity index was 1,17 (1,02-1,77) and 1,22 (1,09-1,29), respectively. Median BED10 was 100 Gy (53,62-151,2) and median beam on time was 26 minutes (12-42). Results: Patients were evaluated on January 2022. The median follow-up was 21 months (2-33). The median age was 68 (53-80) and 40% of the cases were adenocarcinoma. Two patients diagnosed with radiologically. Median lesion size was 13 mm (9-27). SBRT was applied to 13 primary tumors, 3 lung metastases and 7 lymph nodes. At initial evaluation, complete, partial and stable response was found 30%, 65% and 5%, respectively. During the follow-up, 3 patients locally recurred at a median of 11 months (9-14). The median and one-year local recurrence free survival was 22 months, and 89%. Acute and late grade 1-2 pulmonary complications was seen in 10 patients in a median of 7 months (2-13). While the cause of death in 6 cases was existent cardiac morbidity, covid19 pneumonia, lung infection (2) and progression (2), it was unknown in 1 patient. The median and one-year survival was 23 months and 95%. Conclusions: LOT module of the CK-M6 Xsight lung tracking system allows for the application of fiducial-free motion management strategies. The advantage of our study is that the most appropriate tracking modality can be selected prospectively before treatment. In our study, excellent local control with a median survival of 23 months for primary and metastatic lung cancer. With a median treatment time 26 minutes, noninvasive CK-M6 based SBRT was efficient, safe and comfortable treatment in lung cancer. Keywords: lung cancer, Cyberknife-M6, stereotactic body radiotherapy

7.
Journal of Thoracic Oncology ; 17(9):S130-S131, 2022.
Article in English | EMBASE | ID: covidwho-2031505

ABSTRACT

Introduction: There is a subset of NSCLC patients ineligible for benefit from TKIs/Immunotherapy (e.g. STK11 mutation conferring resistance to Immunotherapy). Besides, many patients cannot afford these therapies. Metformin has anticancer properties acting both on glycolytic metabolism and tumor microenvironment. In vitro studies suggest synergism between metformin and pemetrexed. STK11 deficient cell lines are more sensitive to metformin. Clinical studies combining metformin with chemotherapy are limited by small sample size. We conducted an exploratory phase-2 clinical trial of metformin with pemetrexed/carboplatin in advanced non-squamous NSCLC. Methods: This was a single center, open label, single arm phase 2 clinical trial with a Simon’s two stage design. The null hypothesis was that the combination would not improve the 6-month PFS rate by 15%, from 50%. Treatment-naive, non-diabetic patients aged 18-75 years with NSCLC (adenocarcinoma/not-otherwise-specified) with stage IV disease having ECOG PS 0-2 with unmutated EGFR/ALK and without brain metastasis or with asymptomatic brain metastases were treated with pemetrexed-carboplatin chemotherapy and metformin for six months. The primary outcome was 6-month progression free survival (PFS) rate. Secondary outcomes were safety, overall survival (OS), overall response rate (ORR), proportion of STK 11 mutation and effect of STK 11 mutation on 6-month PFS rate. PFS and OS were estimated using the Kaplan-Meier method. Targeted sequencing was attempted for available tissue specimens. Results: The first interim analysis was performed after enrollment of 26 patients for the first stage (before the target accrual of first stage was reached) due to slow accrual, in view of COVID pandemic. The study was terminated after first stage for futility. The median age of patients in the study was 52 years (range, 30 to 68) and 18 patients (69.0%) were males. Half of the patients had ECOG-PS 2. Brain metastases were present in eight (31%) patients and among these four (50%) were symptomatic at presentation. The median follow-up time was 25 months. The median PFS was four months. 6-month PFS rate was 28% (95% CI - 0.12 to 0.46). Of the 25 evaluable patients, five (20%) had a partial response, and eight (32%) had stable disease;13 (52%) of the patients had disease control. The median OS was 16 months. During combined therapy, 14 (54%) and 3 (11%) patients had any grade and grade 3 anemia respectively. One patient had grade 3 neutropenia. Among non-hematological toxicities, gastrointestinal toxicities (nausea, vomiting and diarrhea) were the most common. No grade 4 toxicities were reported. There were no treatment discontinuations, however treatment delay due to grade three toxicities was present in two patients. Dose modification for Metformin was required in four patients. Targeted Sequencing was possible in nine cases. Two of these patients had STK11 mutation and an associated bad outcome (PFS < 2 months). Conclusions: We could not demonstrate the benefit of combination of Metformin with pemetrexed-carboplatin in terms of improvement in 6-month PFS rate. The addition of metformin to pemetrexed-carboplatin has an acceptable safety profile. Future trials should test metformin in specific subsets (STK11 mutated) and in combination with immunotherapy and TKIs. Keywords: Metformin, NSCLC, STK11

8.
Journal of Thoracic Oncology ; 17(9):S20, 2022.
Article in English | EMBASE | ID: covidwho-2031501

ABSTRACT

Introduction: The COVID-19 pandemic led to worldwide barriers to access to operating rooms;some multidisciplinary thoracic oncology teams pivoted to a paradigm of stereotactic ablative radiotherapy (SABR) as a bridge to provide radical-intent treatment combining immediate SABR followed by planned surgery when surgical resource constraints ameliorated. This pragmatic approach, termed SABR-BRIDGE, was instituted with prospective data collection at four institutions (3 Canada, 1 USA);herein we present the surgical and pathological results from this approach. Methods: Eligible participants had early-stage presumed or biopsy-proven lung malignancy that would otherwise be surgically-resected. SABR was delivered using standard institutional guidelines with one of three fractionation regimens: 30-34 Gy /1 fraction, 45-55 Gy/3-5 fractions, or 60 Gy/8 fractions. Surgery was recommended at a minimum of 3 months following SABR with standardized pathologic assessment of resected tissue. A pathological complete response (pCR) was defined as absence of viable cancer, and a major pathologic response (MPR) was defined as ≤10% viable tissue. Results: Seventy-five participants were enrolled, of which 72 received SABR. Following SABR, 26 patients underwent resection, while 46 did not;reasons for not undergoing surgery included metastasis (n=2), non-cancer death (n=1), awaiting lung surgery (n=13) and patient choice given favorable post-SABR imaging response (n=30). Of 26 patients who underwent resection, 62% had a pre-treatment biopsy. The most common SABR regimens were 34 Gy /1 fraction (31%) and 48 Gy in 3-4 fractions (31%). SABR was well-tolerated, with two grade 1 toxicities (pain, 7.7%), and one grade 3 pneumonitis (3.8%). Median time-to-surgery was 4.5 months from SABR completion (range:2-17.5 months). Most had minimally-invasive surgery (n=19, 73%) with 4 patients (15%) requiring conversion to thoracotomy, and 3 (12%) had planned open operation. Surgery was reported as being more difficult because of SABR in 38% (n=10). There were two intraoperative complications (7.7%, pulmonary artery injury), and 8 patients with post-operative complications (31%, all grade 2, most commonly air leaks [n=5]). The amount of residual primary tumor ranged from 0% to 90%. Thirteen (50%) had pCR while 19 (73%) had MPR. Rates of pCR were higher in patients operated upon at earlier time points (75% if within 3 months, 50% if 3-6 months, and 33% if ≥6 months). Rates of pCR were higher in patients without pre-treatment tissue diagnosis (91% versus 20% in those without and with tissue diagnosis, respectively). In 31% (n=8) of patients, nodal disease was discovered on resection, with half being N2 (4/26=15%). Conclusions: The SABR-BRIDGE approach allowed for delivery of treatment with minimal upstaging during a period of operating room closure & high risk for patients. Surgery was well-tolerated. However, most patients who received SABR did not proceed to surgery, limiting precise estimates of pCR rates. However, the reported pCR rate is consistent with previous phase II trial data. Keywords: lung surgery, SBRT, Multi-modal therapy

9.
International Journal of Molecular Sciences ; 23(17):9593, 2022.
Article in English | ProQuest Central | ID: covidwho-2023743

ABSTRACT

Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I-like receptors (RLRs) are major elements of the innate immune system that recognize pathogen-associated molecular patterns. Single-nucleotide polymorphisms (SNPs) in the TLR, NLR, and RLR genes may lead to an imbalance in the production of pro- and anti-inflammatory cytokines, changes in susceptibility to infections, the development of diseases, and carcinogenesis. Acute myeloid leukemia (AML) is a bone marrow malignancy characterized by uncontrolled proliferation of transformed myeloid precursors. We retrospectively analyzed 90 AML patients. We investigated the effect of fifteen SNPs located in the genes coding for RLR1 (rs9695310, rs10738889, rs10813831), NOD1 (rs2075820, rs6958571), NOD2 (rs2066845, rs2066847, rs2066844), TLR3 (rs5743305, rs3775296, 3775291), TLR4 (rs4986791, rs4986790), and TLR9 (rs187084, rs5743836). We observed that TLR4 rs4986791, TLR9 rs5743836, and NOD2 rs2066847 were associated with CRP levels, while RLR-1 rs10738889 was associated with LDH level. Furthermore, we found TLR3 rs5743305 AA to be more common in patients with infections. We also found TLR9 rs187084 C to be associated with more favorable risk, and RLR-1 rs9695310 GG with higher age at diagnosis. In conclusion, the current study showed that SNPs in the genes encoding TLRs, NLRs, and RLRs may be potential biomarkers in patients with AML.

10.
Gut ; 71(Suppl 2):A142-A143, 2022.
Article in English | ProQuest Central | ID: covidwho-2020133

ABSTRACT

BackgroundPET scan is widely used not only to diagnose malignancy and its staging, but a small proportion of patients do have false-positive results. EUS now is a well-established modality to get tissue diagnosis, and with multi-target approach can help stage disease more accurately with histopathological results. We share our experience with EUS-M cases with different variety of malignancies.MethodsA total of 25 cases underwent EUS-M from June 2020 till June 2022. Informed consent was obtained, and with Covid screen test with PCR was performed before the procedure. Procedures were done with all SOPs as per institutional guidelines. 22G FNB needle was used in 24 cases, 25G needle in 01 case;Franseen design with the capillary suction method was used to obtain visible core samples for histopathology without ROSE. All cases have confirmed the histopathological diagnosis with the same pathology from other site of Biopsy. Order of Biopsy was Nodes→ Liver metastatic lesion→ Primary Tumour. In cases of nodes mediastinal→ porta-hepatis/pancreatic→ Para-aortic. All samples were adequate for making a confirmatory diagnosis on the tissue sample.ResultsAmong total of 25 cases, Age 54 Mean (22–77) with 16 Males. Duration of procedure 38 Minutes Mean (20–85). Cases with multiple lymphadenopathy from different anatomical regions were 09, while other sites included Liver for metastasis and Primary tumour from pancreas/CBD/GB in 16 cases. Multiple site single pass was performed in 24 cases. 19 cases had malignant pathologies. Final diagnosis of the Disease was pancreatic adenocarcinoma 07, NETs 02, Lymphoma 04, GB Adenocarcinoma/Cholangiocarcinoma 06 and metastatic RCC 01, TB 01. 04 cases had benign disease. All procedures were done under Conscious sedation as day care procedure. There were no immediate or early complications in all cases.ConclusionsEUS-M is a safe and accurate modality to stage malignancy with superiority over PET Scan to obtain a histological diagnosis.

11.
Gut ; 71(Suppl 2):A142, 2022.
Article in English | ProQuest Central | ID: covidwho-2020132

ABSTRACT

BackgroundEndoscopic Ultrasound (EUS) has emerged as a useful tool to obtain tissue acquisition for diagnosis. In mediastinology, EUS plays its supportive role in certain areas in mediastinum to obtain via trans-oesophageal route safely and accurately tissue diagnosis from lesions suspected likely malignancy either lung pathologies or metastasis from other primaries. In third-world countries, tuberculosis is also commonly encountered along with it. We share our initial experience of different pathologies encountered in EUS-guided biopsy of mediastinal lesions.MethodsA total of 21 cases underwent EUS guided Biopsy from June 2020 to June 2022. Informed consent was obtained, and with Covid screen test with PCR was performed before the procedure. Procedures were done with all SOPs as per institutional guidelines. 22G FNB needle in 20 cases and 25G in one case;Franseen design with the capillary suction method was used to obtain visible core samples for histopathology without Rapid-Onsite-Evaluation (ROSE). All cases have adequate sample for histological diagnosis. The post-procedure oral antibiotic was given to all patients.ResultsAmong these cases, 13 were male, with a mean age of 55 years (range 22–87) and a mean duration of procedure 21 minutes (10–35 min). Majority of them;12 cases were malignant pathologies, while the remaining 09 were benign. The number of ‘passes’ with the needle was average 2.5 with single pass 02, two pass 10, three passes 05 and multitarget lesions were 04. There were Mediastinal lesions in 16 cases and mediastinal nodes biopsy in 05 cases. Common tissue diagnoses include Tuberculosis 06, Squamous cell Carcinoma 04, Lymphoma 03, Benign in 02, Sarcomatoid carcinoma 02 and Metastatic renal Cell Carcinoma 01, Metastatic breast 01, Sarcoidosis 01, Solitary fibrous tumour 01. There were no immediate or early complications in all cases.ConclusionsEUS-guided biopsy of lesions in different mediastinal areas is safe and provides tissue diagnosis with high diagnostic accuracy with the use of FNB needles.

12.
BMJ Open ; 12(9), 2022.
Article in English | ProQuest Central | ID: covidwho-2020042

ABSTRACT

ObjectiveTo obtain annual incidence trends, understand clinicopathological characteristics, and forecast the future burden of colorectal cancer (CRC) in Indonesia.Design11-year retrospective cross-sectional study.SettingA national referral hospital in Jakarta, Indonesia.ParticipantsData from 1584 eligible cases were recorded for trends and forecasting analyses;433 samples were analysed to determine clinicopathological differences between young (<50 years) and old (≥50 years) patients.MethodsTrend analyses were done using Joinpoint software, expressed in annual percentage change (APC), and a regression analysis was executed to generate a forecasting model. Patients’ characteristics were compared using χ2 or non-parametric tests.Main outcomesAnalysis of trends, forecasting model, and clinicopathological features between the age groups.ResultsA significant increase in APC was observed among old patients (+2.38%) for CRC cases. Colon cancer increased remarkably (+9.24%) among young patients;rectal cancer trends were either stable or declining. The trend for right-sided CRC increased in the general population (+6.52%) and old patients (+6.57%), while the trend for left-sided CRC was stable. These cases are expected to be a significant health burden within the next 10 years. Patients had a mean age of 53.17±13.94, 38.1% were young, and the sex ratio was 1.21. Prominent characteristics were left-sided CRC, tumour size ≥5 cm, exophytic growth, adenocarcinoma, histologically low grade, pT3, pN0, inadequately dissected lymph nodes (LNs), LN ratio <0.05, no distant metastasis, early-stage cancer, no lymphovascular invasion, and no perineural invasion (PNI). Distinct features between young and old patients were found in the histological subtype, number of dissected LN, and PNI of the tumour.ConclusionsEpidemiological trends and forecasting analyses of CRC cases in Indonesian patients showed an enormous increase in colon cancer in young patients, a particularly concerning trend. Additionally, young patients exhibited particular clinicopathological characteristics that contributed to disease severity.

13.
Oncology Times ; 44(16):15-15, 2022.
Article in English | CINAHL | ID: covidwho-2018115
14.
Frontiers in Immunology ; 13, 2022.
Article in English | EMBASE | ID: covidwho-2009868

ABSTRACT

Extracellular vesicles (EVs) are membrane-bound particles released by cells in various (patho)physiological conditions. EVs can transfer effector molecules and elicit potent responses in recipient cells, making them attractive therapeutic agents and drug delivery platforms. In contrast to their tremendous potential, only a few EV-based therapies and drug delivery have been approved for clinical use, which is largely attributed to limited therapeutic loading technologies and efficiency. As EV cargo has major influence on their functionality, understanding and translating the biology underlying the packaging and transferring of biomolecule cargos (e.g. miRNAs, pathogen antigens, small molecule drugs) into EVs is key in harnessing their therapeutic potential. In this review, through recent insights into EVs’ content packaging, we discuss different mechanisms utilized by EVs during cargo packaging, and how one might therapeutically exploit this process. Apart from the well-characterized EVs like exosomes and microvesicles, we also cover the less-studied and other EV subtypes like apoptotic bodies, large oncosomes, bacterial outer membrane vesicles, and migrasomes to highlight therapeutically-diverse opportunities of EV armoury.

15.
Journal of Clinical Oncology ; 40(16), 2022.
Article in English | EMBASE | ID: covidwho-2009662

ABSTRACT

Background: The ECOG-ACRIN Tomosynthesis Mammographic Imaging Screening Trial (TMIST), which opened in 2017, is a randomized trial designed to assess whether Tomosynthesis Mammography (TM) should replace Digital Mammography (DM) for breast cancer screening. It is hypothesized that women assigned to TM for 3-5 screening rounds will have fewer advanced breast cancers than the women assigned to DM. Advanced cancers are those that have distant metastases or positive nodes, are invasive tumors greater than or equal to 2.0 cm in size, or are invasive tumors greater than 1.0 cm in size that are triple negative or HER 2+. The initially planned enrollment of 164,946 women was due to be completed by the end of 2020, with follow-up concluded by 2025. There were substantial challenges in meeting this timeline, including the organizational and funding structure of the NCI National Clinical Trials Network which is dependent upon sites using their existing staffing resources (not always readily available at the time of study activation). This led to longer than anticipated start of enrollment for most interested sites and lower than anticipated annual enrollment per participating site based ultimately on the staffing support that could be allocated to manage TMIST. In addition, research staffing shortages and periodic research operations closures due to COVID-19 have also impacted enrolling TMIST sites, though unevenly, since the start of the pandemic. Enrollment plateaued at approximately 2,100 subjects per month by the end of 2020. With that accrual rate expected, the trial design was modified to reduce the sample size so that the study could be completed by 2027. Methods: With the approval of the NCI CIRB, we changed how the primary endpoint measure for TMIST is assessed from the number of advanced cancers that occur by 4.5 years after randomization to the time from randomization to occurrence of advanced cancers. All advanced cancers occurring within 7 years of randomization are now included and all participants followed for at least three years. In addition, the power of the study of the study was modified from 0.9 to 0.85, while the originally assumed effect size at 4.5 years was retained These changes allowed a reduction of sample size to 128,905, with subject recruitment projected to end in 2024. As of February 14, 2022, there are 125 sites open, 114 in the U.S. and 11 in other countries, with an additional 31 sites planning to open. As of February 14, 2022, a total of 63,845 women have been enrolled in the trial worldwide at 115 sites, with 20% of US participants self-identifying as belonging to minority racial and ethnic groups and 70% consenting to optional blood and/or buccal cell collection.

16.
Journal of Clinical Oncology ; 40(16), 2022.
Article in English | EMBASE | ID: covidwho-2009661

ABSTRACT

Background: Uveal melanoma is a rare cancer. Up to 50% of patients (pts) develop metastasis, mainly hepatic. Overall survival in metastatic pts is 12 months (mo), contrasting with a good overall condition until death. To evaluate the impact of integrating early palliative care on patient needs and self-efficacy, we designed a comparative randomized trial in MUM pts. Methods: 162 pts will be randomized (1:2) between the control and the experimental groups in two French centres (Institut Curie-Paris and Centre Antoine Lacassagne-Nice). In the control group, palliative care is introduced according to international guidelines. In the experimental group, it is added earlier, concomitant to the announcement of metastases by the medical oncologist. The main objective is to assess if early supportive care impacts on patient psychological needs at 6 mo, versus standard of care, based on the SCNS-SF34 questionnaire. Secondary objectives include patient's other needs at 6 and 12 mo, quality of life (QLQC30), progression-free and overall survival, and partners' needs (SCNS-P&C). MUM pts, suitable for a treatment with no curative intent, ECOG PS 0-1, with no physical or biological sign of disease, and capable of filling questionnaires are eligible. Questionnaires are completed by all pts at each oncological visit (baseline, 3, 6, 9 and 12 mo). Supportive care visits take place every 6 weeks if needed and address patient's information needs, disease and treatment understanding, social and psychological status, symptoms, and partners' involvement. Prognostic uncertainty and disease seriousness in the absence of symptom is addressed depending on pts' expressed needs. Medical oncologists and supportive care physicians from both centres attend communication skill training provided by an expert during the study. Analyses: SCNS-SF34 psychological needs scale scores at 6-mo will be compared with a Student's t-test, in an ITT analysis. For 10 points mean score difference expected between groups (within standard deviation of 20 points) and a two-sided type 1 error of 5%, inclusion of 54 pts (control group) and 108 pts (experimental group) provides the study 85% of power. The planned inclusion period is 3 years, pts will be followed for one year, for a total study duration of 4 years. From July 2020 to January 2022, 63 pts have been enrolled in the trial;2 pts declined. Five pts were removed early from the study: one for consent retrieval, 4 for early death due to metastasis. COVID-19 delayed enrollment for 5 months. We plan to complete the study Q4 2023 and to analyze the data Q4 2024.

17.
Journal of Clinical Oncology ; 40(16), 2022.
Article in English | EMBASE | ID: covidwho-2009660

ABSTRACT

Background: CSCC is the second most common skin cancer with an estimated incidence of 1 million cases per year in the US. While the surgical cure rate for CSCC is > 95%, some pts have high risk of recurrence as assessed by immune status, primary disease stage, extent of nodal involvement, presence of extracapsular extension (ECE), and prior treatment. Postoperative RT is recommended for these pts but relapse with locoregional recurrence or distant metastases may still occur. C-POST is evaluating the efficacy of cemiplimab as adjuvant therapy for pts with high-risk CSCC. Here, we provide summary of the most recent study protocol amendment. Methods: C-POST is a randomized, placebo-controlled, double-blind, multicenter Phase 3 study to evaluate cemiplimab as adjuvant treatment for pts with high-risk CSCC, based on surgical and clinicopathologic findings, who completed surgery and postoperative RT (minimum total dose 50Gy, within 10 weeks before randomization) (NCT03969004). Pts with at least one of the following high-risk features are eligible: (1) nodal disease with (a) ECE and at least one node ≥20 mm or (b) at least three lymph nodes positive on surgical pathology report, regardless of ECE;(2) in-transit metastases;(3) T4 lesion;(4) perineural invasion;and (5) recurrent CSCC with at least one other risk factor. Pts with CSCC involvement in at least three lymph nodes (feature 1b) were added to the eligibility criteria, as this group was found to be at similar risk of CSCC recurrence as the initially planned study population. Protocol amendment now allows patients with chronic lymphocytic leukemia (CLL) who are not on active treatment to be enrolled. The study has two parts. In Part 1 (blinded), pts are randomly assigned 1:1 to receive cemiplimab 350 mg or placebo intravenously every 3 weeks for 12 weeks, followed by cemiplimab 700 mg or placebo every 6 weeks for 36 weeks. In optional Part 2 (unblinded), pts in the placebo arm who experience disease recurrence and pts in the cemiplimab arm who experience disease recurrence ≥3 months after completion of 48-week treatment in Part 1 are eligible to receive open-label cemiplimab for up to 96 weeks. The trial is expected to enrol 412 pts from about 100 sites in North and South America, Europe, and Asia-Pacific regions. Key primary objective is to compare disease-free survival;secondary objectives include evaluating overall survival, freedom from locoregional relapse, and distant relapse with adjuvant cemiplimab versus placebo in patients with high-risk CSCC. This study is once again open for enrolment following interruptions owing to the COVID-19 pandemic.

18.
Journal of Clinical Oncology ; 40(16), 2022.
Article in English | EMBASE | ID: covidwho-2009659

ABSTRACT

Background: Gal-3 is a protein that binds specifically to N-acetylglucosamine-expressing carbohydrates, which are upregulated on key tumorigenic cell surface proteins. Gal-3 is widely over-expressed in the tumor microenvironment and is generally linked to poor outcomes. Gal-3 regulates immune cell function of T cells and macrophages, and promotes neovascularization and fibrosis [Peng Cancer Res 2008;Markowska J Biol Chem 2011;Kouo Cancer Immunol Res 2015]. Gal-3 sequesters interferon gamma, reduces T-cell influx, and contributes to tumor cell evasion of the immune system via LAG-3 activation [Chen PNAS 2009;Gordon-Alonso Nat Commun 2017]. Gal-3 has been identified as a marker of resistance to checkpoint inhibitors (CPIs);patients with stage IV NSCLC with high Gal-3 levels (> 70% Gal-3 immunohistochemical staining) have been shown to be resistant to the CPI pembrolizumab [Capalbo Int J Mol Sci 2019]. Animal data indicate synergy between CPI therapy and Gal-3 inhibition [Vuong Cancer Res 2019;Zhang FEBS Open Bio 2021]. Thus, inhibiting Gal-3 together with CPI-based immunotherapy may enhance tumor-specific immune responses, and overcome CPI resistance. Methods: GALLANT-1 (NCT05240131) is a 3-part, placebo-controlled phase Ib/IIa trial that will investigate safety and efficacy of GB1211 (a Gal-3 inhibitor) + atezo vs placebo + atezo in patients with advanced NSCLC. Part A will include 8-12 patients and study safety and tolerability of 200 mg and 400 mg GB1211 twice-daily + atezo (open-label). Primary endpoint is number of adverse events (AEs) after 12 weeks' treatment and will determine the dosage for Part B. Part B will include 75-94 patients, and is a randomized, double-blind study of GB1211 + atezo or placebo + atezo. Primary endpoints are safety (number of AEs) and efficacy (percentage change from baseline in the sum of longest diameter of target lesions after 12 weeks' treatment). Part C is an expansion study including patients from Parts A and B, with safety and efficacy assessments. Eligibility criteria: advanced or metastatic stage IIIB or IV NSCLC adenocarcinoma;measurable disease per RECIST v1.1;expression of programmed death ligand-1 on ≥50% of tumor cells;eligible for 1200 mg atezo every 3 weeks. Exclusion criteria: symptomatic, untreated, or actively progressing central nervous system metastases;prior systemic chemotherapy for treatment of recurrent advanced or metastatic disease, except if part of neoadjuvant/ adjuvant therapy;prior treatment with immune CPIs and/or GB1211;presence of EGFR mutation and ALK, ROS1, and RET alterations;treatment with antineoplastic or systemic immunotherapeutic agents prior to first GB1211 dose;severe infectious disease < 4 weeks prior to first GB1211 dose;active hepatitis B or C, HIV, or COVID-19. The study is being initiated;updated enrollment status will be presented at the meeting.

19.
Journal of Clinical Oncology ; 40(16), 2022.
Article in English | EMBASE | ID: covidwho-2009651

ABSTRACT

Background: Older patients with cancer are particularly vulnerable, and the risk of mortality and morbidity during this pandemic is high. Comprehensive geriatric assessment (CGA) helps in predicating toxicity and improve outcomes. SAOP3 is validated geriatric screening tool that can efficiently identify deficits in different GA domains. It was developed to determine when a multidisciplinary team consultation with GA-intervention is required. Methods: We performed a retrospective review of institutional cancer registry. We compared 2 groups of cancer patients ≥ 70 years old who completed SAOP3 questionnaire in the pre-COVID (9/1/2019- 3/10/2020) and during the pandemic period (3/11/2020-12/ 31/2020). Fisher's exact test was used to statistical analysis. Analytical models were adjusted for age, cancer histology, stage, therapy type, and GA variables. Results: 951 patients were included (499 prepandemic, 452 during pandemic). Median age was 76.6 yrs. (range = 71-86). A 50.7% male, 48.3% female and 34% (323) have metastatic disease. The capture and completion rate of SAOP3 were 82% (779) and 86% (817) respectively. There was a significant psychosocial impairment during the pandemic. More patients were feeling depressed 26% (118) during Vs. 3% (15) prior pandemic (P < 0.001). The caregiver availability was different with 47% (212) during pandemic compared to 52% (259) in pre-pandemic (P = 0.0013). There was a statistically significant difference in the fall history with 4% (20) in pre-, in contrast to 10% (45) during pandemic (P = 0.003). There was a numerical difference in the cognitive impairment during the pandemic in compared to the pre-COVID [34% (171), 52% (235) respectively], but it was not statistically significant (P = 0.154). There was no difference observed in nutritional domains between the two groups. Conclusions: Data regarding patients' domains of a CGA are crucial for optimal care. Screening with the SAOP3 questionnaire captured significant changes in CGA domains associated with the pandemic. These findings also suggest that Integration of high-yield brief geriatric screening tools such as SAOP3 is feasible in busy practice during the pandemic. It can help identify specific impairment of older cancer patients and trigger appropriate interventions to improve the quality of life and clinical outcomes.

20.
Journal of Clinical Oncology ; 40(16), 2022.
Article in English | EMBASE | ID: covidwho-2009624

ABSTRACT

Background: Vaccination against COVID-19 decreases the risk of severe COVID 19 disease, hospitalization and death. Despite widespread recommendation from different cancer societies, vaccine hesitancy remains an issue in developing countries. Methods: Records of patients with cancer who received COVID-19 vaccination from March 1, 2021 and December 1, 2021, at Todua Clinic were analyzed retrospectively. Patient reported adverse effects (AE), vaccine related treatment interruptions, COVID -19 infection, and hospitalization rates were recorded. Results: A total of 1728 patients with cancer were treated at Todua Clinic during the study period. Of 177 (10%) patients who received Covid-19 vaccine, 63% were female and 34% were male. All patients were White. Mean age was 62 years. Majority of patients had solid cancer (93%) and only 7% had hematologic malignancies. A total of 76 (43%) patients had metastatic disease. Nearly half (47%) of patients were receiving cytotoxic chemotherapy, while others were receiving different treatment modalities (hormone therapy (33%), concurrent chemo-radiation (9%), chemo-immunotherapy (4%), targeted therapy (3%), immune therapy (2%), radiation therapy (2%)). Majority of the patients were vaccinated during the treatment process (61%), while 18% received covid-19 vaccine prior to treatment initiation and 21% patients received the vaccine after completion of treatment. A total of 124 patients (70%) were vaccinated with Pfizer-BioNTech, 33(19%) patients had received Sinopharm (Beijing), 14(8%) patients were vaccinated with The Oxford/ AstraZeneca and 6 (3%) patients with Sinovac/CoronaVac. Only 13 (7%) patients received a booster dose (BD). Injection site pain was main AE for all vaccines (AstraZeneca 50%, Pfizer 33%, Sinopharm 45%, Sinovac 50%). Fever was reported in 14% of patients vaccinated with AstraZeneca, and 2% of those who received Pfizer vaccine. There were isolated cases of lymphadenopathy, fatigue, loss of appetite, joint and muscle pain after Pfizer vaccine and one case of polyneuropathy after a booster dose (Pfizer). No treatment interruptions were attributed to vaccination. Only 23 patients (13%) had confirmed COVID-19 infection (post AstraZeneca 1, Pfizer 13, Sinopharm 8, Sinovac 1). Only 1 case of hospitalization was reported after Sinopharm vaccine. No death was reported due to COVID-19 infection. Majority of patients (80%) were vaccinated following recommendation from their treating oncologist. Conclusions: In our study, COVID-19 vaccination was found to be safe for patients with cancer, and performed well with only one COVID-19 related hospitalization and no deaths. Vaccination rates among cancer patients are marginal in Georgia, and institutional and national policies are needed.

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