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Background: During the coronavirus disease 2019 (COVID-19) pandemic, established best practices in cancer care were modified to diminish the risk of COVID-19 infection among patients and health-care workers. Objective(s): We aimed to study the modifications in cancer-directed therapy during the first wave of the COVID-19 pandemic. Material(s) and Method(s): A cross-sectional study of patients with cancers of the head and neck, thoracic, urologic, and central nervous systems who visited the medical oncology department of the Tata Memorial Hospital, Mumbai, India, between April 22, 2020 and June 01, 2020, was conducted. Data were prospectively collected in an online pro forma and supplemented from the electronic medical records. Result(s): Of a total of 514 patients, 363 (71%) were men. The most common malignancy was lung cancer in 234 patients (46%). Cancer-directed therapy was modified in 83 patients (16%). Deviations consisted of modification of the chemotherapy regimen (48%), temporary discontinuation of chemotherapy in 37%, and interim chemotherapy to delay surgery in 5%. Changes in the chemotherapy regimen included a shift to a less intensive regimen in 45%, changing from intravenous to oral in 40%, and less frequent dosing of immunotherapy in 7%. Considering missed appointments as a deviation from planned cancer therapy, 68% of patients had a deviation in the standard planned cancer care. Conclusion(s): Almost two-thirds of the patients could not reach the hospital during the COVID-19 pandemic lockdown in India. Of those who could reach the hospital, one of out every six patients with cancer had a change in their cancer-directed treatment, half of which consisted of a modification in the standard chemotherapy regimens. The effects of these therapy deviations are likely to be long-lasting. (Clinical Trials Registry-India, CTRI/2020/07/026533).Copyright © 2023 Neurology India, Neurological Society of India Published by Wolters Kluwer - Medknow.
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Background: Anticipating the correlation between SARS-CoV-2 infection and ‘triplenegative breast cancer (TNBC)' remains challenging. It has been reported that people currently diagnosed with cancer have a higher risk of severe complications if they are affected by the viral infection. Cancer treatments, including chemotherapy, targeted therapies, and immunotherapy, may weaken the immune system and possibly cause critical lung damage and breathing problems. Special attention must be paid to the ‘comorbidity condition' while estimating the risk of severe SARSCoV- 2 infection in TNBC patients. Hence the work aims to study the correlation between triplenegative breast cancer (TNBC) and SARS-CoV-2 using biomolecular networking.Methods: The genes associated with SARS CoV-2 have been collected from curated data in Bio- GRID. TNBC-related genes have been collected from expression profiles. Molecular networking has generated a Protein-Protein Interaction (PPI) network and a Protein-Drug Interaction (PDI) network. The network results were further evaluated through molecular docking studies followed by molecular dynamic simulation.Results: The genetic correlation of TNBC and SARS-Cov-2 has been observed from the combined PPI of their proteins. The drugs interacting with the disease's closely associated genes have been identified. The docking and simulation study showed that anti-TNBC and anti-viral drugs interact with these associated targets, suggesting their influence in inhibiting both the disease mutations.Conclusion: The study suggests a slight influence of SARS-CoV-2 viral infection on Triple Negative Breast Cancer. Few anticancer drugs such as Lapatinib, Docetaxel and Paclitaxel are found to inhibit both TNBC and viral mutations. The computational studies suggest these molecules are also useful for TNBC patients to control SARS-CoV-2 infection.
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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.
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Objective: Adverse drug reactions increase morbidity and mortality, prolong hospital stay and increase healthcare costs. The primary objective of this study was to determine the prevalence of emergency department visits for adverse drug reactions and to describe their characteristics. The secondary objective was to determine the predictor variables of hospitalization for adverse drug reactions associated with emergency department visits. Method(s): Observational and retrospective study of adverse drug reactions registered in an emergency department, carried out from November 15th to December 15th, 2021. The demographic and clinical characteristics of the patients, the drugs involved and the adverse drug reactions were described. Logistic regression was performed to identify factors related to hospitalization for adverse drug reactions. Result(s): 10,799 patients visited the emergency department and 216 (2%) patients with adverse drug reactions were included. The mean age was 70 +/- 17.5 (18-98) years and 47.7% of the patients were male. A total of 54.6% of patients required hospitalization and 1.6% died from adverse drug reactions. The total number of drugs involved was 315 with 149 different drugs. The pharmacological group corresponding to the nervous system constituted the most representative group (n = 81). High-risk medications, such as antithrombotic agents (n = 53), were the subgroup of medications that caused the most emergency department visits and hospitalization. Acenocumarol (n = 20) was the main drug involved. Gastrointestinal (n = 62) disorders were the most common. Diarrhea (n = 16) was the most frequent adverse drug reaction, while gastrointestinal bleeding (n = 13) caused the highest number of hospitalizations. Charlson comorbidity index behaved as an independent risk factor for hospitalization (aOR 3.24, 95% CI: 1.47-7.13, p = 0.003, in Charlson comorbidity index 4-6;and aOR 20.07, 95% CI: 6.87-58.64, p = 0.000, in Charlson comorbidity index >= 10). Conclusion(s): The prevalence of emergency department visits for adverse drug reactions continues to be a non-negligible health problem. High-risk drugs such as antithrombotic agents were the main therapeutic subgroup involved. Charlson comorbidity index was an independent factor in hospitalization, while gastrointestinal bleeding was the adverse drug reaction with the highest number of hospital admissions.Copyright © 2022 Sociedad Espanola de Farmacia Hospitalaria (S.E.F.H)
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This work studied the antioxidant and anti-breast cancer properties of hyaluronidase, extracted from a potential marine strain, Staphylococcus aureus (CASMTK1), isolated from Parangipettai coastal waters in southeast coast of India. The Staphylococcal enzyme production was tested under different carbon and nitrogen sources;and recorded the maximum production when the microbial strain was cultured with starch as the carbon source and ammonium sulphate as the inorganic nitrogen source with the enzyme production of 92.5 U/mL and 95.0 U/mL, respectively. The hyaluronidase enzyme production was also tested in different pH and temperature;and recorded the maximum yield of 102.5 U/mL in pH 5 and that of 95.5 U/mL in 45 °C. The partially purified enzyme was subjected to FTIR and FT Raman technique and found the presence of the amide- I and II, Carboxyl, N-H bending, C-H stretching and α-helices and β-sheet proteins between wave number 1500–1700 cm−1. The partially purified enzyme also exhibited strong antioxidant and in-vitro breast cancer properties. The enzyme showed the highest hydroxyl radical scavenging activity of 79% at the 50 µg/mL concentration, and this activity increased in a dose-dependent manner. The enzyme inhibited proliferation of the breast cancer cell line of MCF-7, and it caused 100% cell death at the concentration of 80 µg/mL. The enzyme generated capacity of producing free radicles that damage the cancer cells, and this effect was very nearer to the standard drug, paclitaxel. The enzyme damaged the cancer cells and induced apoptosis in 78% of cancer cells as evident by condensed or fragmented chromatin at 40 µg/mL. Further purification of the enzyme, analysis of its molecular aspects, and elucidation of exact mechanisms of its biological activities will throw new light on the utility of staphylococcal hyaluronidase in anticancer chemotherapy.
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COVID-19 is a disease caused by SARS-CoV-2 that can trigger respiratory tract infection. Due to its tendency to affect the upper respiratory tract (sinuses, nose and throat) or lower respiratory tract (windpipe and lungs), this disease is life-threatening and affects a large number of populations. This virus's unique and complex nature enhances the scope to look into the direction of herbal plants and their constituents for its prevention and treatment. The herbal remedies can have preventive as well as therapeutic actions. This review focuses on various aspects of using herbal medicines for COVID-19, as herbal constituents may also have adverse effects. Various studies revealed that some medicinal plants show life-threatening adverse effects, so selecting plants, and their related studies should be appropriate and strategic. This article includes various factors that should be considered before herbal drug use in COVID-19 patients. These are clinical trials, safety, molecular mechanism, and self-medication, which have been elaborated. This article also discusses the targets of covid-19 and different coronavirus strains. As before, treatment diagnosis of the disease is very important. Various patents have been filed and granted for its proper diagnosis so that its treatment can be easy.Copyright © 2022 Society of Pharmaceutical Sciences and Research. All rights reserved.
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Since Coronavirus Disease 2019 (COVID-19) was declared pandemic in March 2020, there have been 545.226.550 cases up to 4 July 2022 (1). Several studies concluded that patients (pts) with cancer are at increased risk of COVID-19 infection, morbidity and mortality. Those undergoing neoadyuvant treatment are at particularly risk of disease progression if chemotherapy or surgery are delayed. Also, is known that a higher NLR (neutrophil to limphocyte ratio) is related to worse outcomes (3). Our hospital is located at the Northwest of Spain and in the last months we noticed a never seen number of infections in cancer population. The aim of this study is to evaluate the severity of COVID19 and its impact on chemotherapy and surgery delay in pts undergoing neoadjuvant chemotherapy breast cancer. METHOD(S): We conducted a ambispective, unicenter, observational study of breast cancer pts, treated with neoadjuvant chemotherapy, between March 2020 and May 2022 at University Hospital A Coruna (Spain). We analyzed type of infection, need of hospitalization, chemotherapy and surgical delay, and its association with tumor type;BRCA germline mutation;clinical stage;treatment;vaccination status;and neutrophils, lymphocytes, and NLR before COVID-19 disease. RESULT(S): During the study period, from 1 March 2020 to 31 May 2022, 183 pts underwent neoadjuvant chemotherapy. A total of 23 (12.5%) pts experienced COVID-19 infection, of which 21 were diagnosed between January and May 2022. The median age was 47,91 years [range 33 - 69 years]. Luminal B HER 2 negative comprised the most common molecular subtype (40.9%), followed by Triple Negative (36.4%), Luminal B HER 2 positive (13.6%), and HER 2 enriched (9.1%). Germline mutations in BRCA account for 13.6% pts. At diagnosis, 4.5%, 72.7%, and 22.7% had stages I, II, and III respectively. Chemotherapy treatments included: paclitaxel followed by AdryamicineCyclophosphamide (AC) (45.4%);carboplatin - paclitaxel - trastuzumab - pertuzumab (18,2%);carboplatin - paclitaxel followed by AC (18,2%);KEYNOTE-756: pembrolizumab/placebo - paclitaxel followed by AC (13.7%);and paclitaxel - trastuzumab - pertuzumab followed by myocet - cyclophosphamide - trastuzumab - pertuzumab (4.5%). The association of G-CSF ocurred in 9 pts (40.9%). 22 pts were fully vaccinated, 8 pts (36.4%) with two doses and 13 pts (59.1%) with three doses. 77.3% pts experienced mild respiratory symptoms with 9.1% hospitalizations. The median duration of delays was 15 days for chemotherapy and 29,58 days for surgery. NLR percentil 25 was associated with COVID-19 type of infection. For those pts with a lower rate, infection was asymptomatic and for those with a higher rate symptoms were moderate (X2= 5,119, p = 0,024). CONCLUSION(S): COVID-19 disease become a high prevalent infection in pts undergoing neoadjuvant breast cancer chemotherapy. Most pts are fully vaccinated and experienced an indolent infection. NLR is an easily measurable and cost-effective parameter that could be useful as a prognostic marker of severity in COVID-19. We will continue to follow-up these pts to see the impact of chemotherapy or surgery delay in pathological complete response and disease-free survival until the congress in December 2022.
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Background Large autopsy studies have shown intracardiac metastases in 15% of patients with disseminated cancer. We present a rare case of metastatic squamous cell carcinoma (SCC) of the heart with unknown primary. Case 55-year-old female with DVT, COVID-19 infection and stage IV metastatic SCC of uncertain origin presented with progressive fatigue and dyspnea. She had occlusion of left interlobar pulmonary artery and new large right ventricle (RV) mass consistent with tumor and thrombus invasion. Systemic anticoagulation was initiated. Decision-making Echocardiography showed a large mass in RV measuring 5 cm x 2.5 cm and occupying most of the RV cavity. Though her RV systolic function was reduced, she was unlikely to benefit from surgical resection due to disseminated disease. Piecemeal removal of RV mass alleviated the obstructed RV outflow tract. Histopathology featured squamous cell carcinoma. She had symptom resolution within a week following procedure. The patient was discharged home with oral anticoagulant. On follow up, she had not experienced any worsening of symptoms and changes in RV mass size despite compliance with chemotherapy (carboplatin and paclitaxel) and anticoagulation. Conclusion Metastatic SCC with unknown primary is a rare cause of acute heart failure that highlights the interplay between clinical findings and multimodal cardiac diagnostic imaging. An individualized approach is required for patients, balancing both risks of surgical and percutaneous intervention. [Formula presented]Copyright © 2023 American College of Cardiology Foundation
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BACKGROUND: It is 1 of the standard treatment options for metastasis pancreatic cancer to receive nab-paclitaxel (125 mg/m2) plus gemcitabine (1000 mg/m2) on days 1, 8 and 15 every 28 days. Some patients showed intolerance and inconvenience to this therapeutic regimen. Thus, we conducted this retrospective real-world study to determine the efficacy and tolerability of a modified 21-day nab-paclitaxel plus gemcitabine (nab-P/Gem) regimen for the first-line treatment of locally advanced or metastatic pancreatic cancer. METHODS: Patients with locally advanced and metastatic pancreatic cancer treated with nab-paclitaxel (125 mg/m2) plus gemcitabine (1000 mg/m2) on days 1 and 8 every 21-day at West China Hospital and Shang Jin Hospital of Sichuan University from Mar 2018 to Dec 2021 were reviewed retrospectively. Clinical characteristics of patients were collected. The progression-free survival, overall survival, objective response rate, disease control rate, and toxicity were evaluated. RESULTS: A total of 113 patients who received the modified regimen of 21-day nab-P/Gem chemotherapy were included. The median overall survival was 9.3 months and the median progression-free survival was 4.4 months. The objective response rate and disease control rate were 18.6% and 56.7%, respectively. The median relative dose intensity for this modified regimen was 65%. The adverse events were mild to moderate, and the most common grade 3 or 4 treatment-related adverse events were neutropenia (21%) and leukopenia (16%). CONCLUSIONS: Our study showed that this modified regimen of 21-day nab-P/Gem for locally advanced and metastatic pancreatic cancer had comparable efficacy and tolerable toxicity. This treatment may provide a considerable option for pancreatic cancer patients who desire a modified schedule. The modified regimen of 21-day nab-P/Gem is also an option worth considering during the coronavirus disease 2019 pandemic for minimizing the number of visits and limiting the risk of exposure.
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Antimetabolites, Antineoplastic , Paclitaxel , Pancreatic Neoplasms , Humans , Antineoplastic Combined Chemotherapy Protocols , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Retrospective Studies , Paclitaxel/administration & dosage , Paclitaxel/therapeutic use , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/therapeutic use , GemcitabineABSTRACT
Pandemic was new experience for entire humanity. Medical fraternity was no exception. The cases of mucormycosis were on the rise during the second wave of the pandemic. Presented here are two cases which were combination of two diseases, one of which was squamous cell carcinoma of head and neck region and other one was sinonasal mucormycosis. Both patients were diabetics and had history of Coronavirus Disease-2019 (COVID-19) infection in past. Our literature search doesn't reveal any previously reported cases of this rare combination. There were certain challenges in management. Both diseases were lethal and treatment of one cannot be prioritised over other. Challenges in managing those cases were, reconstruction planning, perioperative management and postsurgery adjuvant therapy. In absence of previous experience to treat this combination or any literature available new treatment protocol were formulated. Cases were discussed in multidisciplinary team meetings and treatment plans were formulated. Mucormycosis and oral squamous cell carcinoma both were operated and reconstructed in same sitting. In one patient revision endoscopic debridement had to be done. Amphotericin B was started once diagnosis was confirmed. Patients were followed-up on weekly basis during first month and imaging was done every 15 days. Both patients had satisfactory recovery without any sign of progression of mucormycosis. Adjuvant radiation was given in both cases at appropriate time. At follow-up both patients were free from disease for six months. From these unique experiences it can be recommended that combination of sinonasal mucormycosis and squamous cell carcinoma of head and neck is very rare. Both diseases can be treated simultaneously. Excision and reconstruction can be done in single sitting. There is no need to delay or avoid adjuvant radiation. Multidisciplinary team approach is the key for treatment.
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Background: Pathological complete response (pCR) is associated with improved prognosis in triple-negative breast cancer (TNBC). Anlotinib, a novel multi-target tyrosine kinase inhibitor that effectively inhibits VEGFR, FGFR, c-KIT, c-MET, and RET, monotherapy has been proven effective in HER-2 negative metastatic breast cancer, but its efficacy in early-stage TNBC is unknown. This phase 2 study aims to evaluate the efficacy and safety of adding anlotinib to neoadjuvant chemotherapy in patients (pts) with primary TNBC. Methods: Pts with clinical stage II/III TNBC were to be treated with 5 cycles of anlotinib (12mg, d1-14, q3w) plus 6 cycles of taxanes (docetaxel 75 mg/m2 or nab-paclitaxel 260 mg/m2, d1, q3w) and lobaplatin (30 mg/m2, d1, q3w), followed by surgery. The primary endpoint was the total pCR (tpCR;ypT0/is ypN0). A Simon's two-stage optimum design was used, and > 5 of 11 pts were required to achieve tpCR in the first stage, with a pre-specified tpCR rate of 54.5% before proceeding to the second stage. A total of 31 participants was required for the study. Results: Six out of 11 pts achieved tpCR in the first stage, reaching the threshold for the second stage. From Jan 2021 to Jan 2022, a total of 22 pts were enrolled and 12 received surgery after the completion of neoadjuvant therapy, but a total of 2 pts withdrew from the study due to the COVID-19 pandemic or serious adverse events. Of the 22 eligible pts, the median age was 49 years (range, 29-64), 64% were postmenopausal, and 73% were nodal involved. At the time of surgery, 58.3% (7/12) achieved tpCR. Of the 9 pts with the node-positive disease at diagnosis, 88.9% (8/9) became ypN0. The results of FUSCC TNBC classification (IHC-based) revealed the tpCR rates were 57.1% (4/7), 100% (3/3), and 0% (0/2) for BLIS subtype, IM subtype and LAR/unknown subtypes, respectively. Biomarker analysis showed the tpCR rates were 100% (3/3) and 100% (4/4) in patients with gBRCA1 mutation and MYC amplification, respectively. The most common grade 3 or 4 treatment-related adverse events were leucopenia (6/22, 27%), neutropenia (6/22, 27%), anemia (5/22, 23%), decreased appetite (5/22, 23%), hypertension (2/22, 9%), ALT increased (1/22, 5%) and oral mucositis (1/22, 5%). No treatment-related deaths occurred. The trial is ongoing. Conclusions: The addition of anlotinib to neoadjuvant chemotherapy showed manageable toxicity and promising antitumor activity for patients with early-stage TNBC.
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Background: This study aimed to investigate the superiority of nab-paclitaxel plus S-1 (AS) over oxaliplatin plus S-1 (SOX) in patients with advanced gastric cancer (AGC). Methods: In this multicenter, randomized, phase III superiority trial, eligible patients with unresectable, locally advanced gastric adenocarcinoma were recruited and randomly assigned (1:1) to receive AS (nab-paclitaxel 260 mg/m2 on day 1 or 130 mg/m2 on days 1 and 8; oral S-1 40-60 mg twice daily for 14 days) or SOX (130 mg/m2 oxaliplatin on day 1; oral S-1 40-60 mg twice daily for 14 days) every 3 weeks for up to six cycles. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival, objective response rate, and safety. Results: Owing to slow enrolment, an unplanned interim analysis was performed, resulting in the early termination of the study on 31 December 2021 (data cutoff). Between March 2019 and March 2021, 97 patients (AS, n = 48; SOX, n = 49) were treated and evaluated for efficacy and safety of AS and SOX. As of the data cutoff, the median follow-up was 23.13 months [95% confidence interval (CI), 13.39-32.87]. The median PFS was 9.03 months (95% CI, 6.50-11.56) in the AS group and 5.07 months (95% CI, 4.33-5.81) in the SOX group, demonstrating a better PFS tendency following AS treatment than SOX treatment (hazard ratio = 0.59; 95% CI, 0.37-0.94; p = 0.03). The most common grade 3 or worse adverse events were anemia, neutropenia, and leukopenia in both groups, with a higher incidence of thrombocytopenia in the SOX group. Conclusion: Although this study was terminated early, the results demonstrated a better PFS tendency in patients with AGC who were treated with AS than in those treated with SOX, with controllable toxicities. Trial registration: Clinical Trials.gov identifiers: NCT03801668. Registered January 11, 2019.
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Background: Induction FOLFOX followed by PET-directed CRT prior to surgery demonstrated positive results in the CALGB 80803 study. We investigated the safety and efficacy of adding D, an anti-PD-L1 antibody, to PET-directed CRT. Methods: Patients (pts) with locally advanced esophageal/GEJ adenocarcinoma were enrolled. Pts received 2 cycles of mFOLFOX6 prior to repeat PET/CT. PET responders (≥35% reduction in SUV (PETr)) received 5-FU/capecitabine and oxaliplatin with RT to 50.4Gy, while induction PET non-responders (PETnr) received carboplatin/paclitaxel with RT. All Pts received D 1,500 mg q4W ×2 starting 2 weeks prior to CRT. Esophagectomy was planned 6-8 weeks after CRT. Pts with R0 resections received adjuvant D 1,500mg q4W ×6. The primary endpoint was the pathologic complete response (pCR) rate. Results: 36 pts were enrolled. Clinical ≥T3 disease was seen in 32 pts (88.9%, cT4 = 3) and ≥N1 in 23 (63.9%) pts. PD-L1 CPS was ≥1 in 25 (71.4%) of 35 tested with 14 (40%) ≥5. Microsatellite instability (MSI) was identified in 3 (8.3%) pts. 25 (70%) pts were PETr. Preop treatment was well tolerated with no new safety signals. Three pts had disease progression prior to surgery. pCR was identified in 8 (22.2%) pts and 22 (64.7%) had major pathologic response (MPR;ypTanyN0 + ≥90% response). Those with MSI tumors had ≥90% treatment response (1 pCR, 1: ypT1aN0 99% response, 1: ypT2N0, 90% response). 17 (73.9%) of 23 cN+ pts had ypN0 disease. MPR was associated with PD-L1 ≥1 (p = 0.03) and with a higher tumor mutational burden (TMB;p = 0.016) on MSK-IMPACT testing. Adjuvant D was commenced in 27 pts, with a median number of 6 cycles. Early discontinuation was due to risks of visits due to COVID19 (4, 15%), progressive disease (3, 11%), late surgical complications (2, 7%) and immune toxicity (1, 4%). With a median follow-up of 30 months, OS rates were 92% [95%CI: 83%-100%] and 85 % [95%CI: 74%-98%] at 12 and 24 months post induction. 12 and 24-month PFS rates were 81% [95%CI: 69%-95%] and 71% [95%CI: 58%-88%] respectively. In the 33 operated pts, 12 and 24-month disease free survival was 82% [95%CI: 70%-96%] and 78% [95%CI: 65%-94%], respectively. In addition to SUV on PET, total lesion glycolysis (TLG) was correlated with pathologic response. In cases with borderline change in SUV, TLG could predict response to treatment. One PETnr with 30.8% reduction in SUV had 88.1% reduction in TLG and pCR. Conversely, a PETr (-36.3%) who had an increase in TLG (39.3%) had only 40% treatment response on pathology. Conclusions: The addition of D to induction FOLFOX and PETdirected CRT prior to surgery is safe and appears effective with a high rate of pathologic response, as well as encouraging survival data. PD-L1 CPS≥1 and higher TMB may be associated with MPR. TLG is a novel PET variable that should be studied prospectively. Additional correlatives and comparison to a cohort treated with standard PET-directed CRT will be presented.
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The coronavirus disease 2019 (COVID-19) was reported in Wuhan, China, in late December 2019 and soon became the most serious global health challenge due to the high rate of human-to-human transmission. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded RNA virus and belongs to the large Coronaviridae family [1]. The pathogenesis of the COVID-19 still remains poorly understood. Cytokine storm, a hyper-inflammatory state, is considered one of the most important causes of respiratory distress syndrome (ARDS) and death in patients with COVID-19. Clinical studies have reported that there is a strong association between the level of inflammatory cytokines and the severity of the COVID-19 [2]. The prognosis of the COVID-19 is good in most patients;however, in a small number of patients, it develops into ARDS and subsequently, death within a short time [1]. Given that there is no specific antiviral drug for the treatment of the disease, suppression of cytokine storms using FDA-approved drugs with multiple mechanisms of action may reduce the COVID-19-related mortality.
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The management of breast cancer patients in the current COVID-19 outbreak is challenging. Myelosuppres-sion associated with cancer treatment may increase the risk of infection in both hospitals and at home. We implemented the following strategy to reduce myelosuppression of adjuvant chemotherapy during the COVID-19 pandemic: (1) changing the original regimen of AC x 4-* wT x 12 to wT x 12-* AC x 4. (2) substitution of standard paclitaxel with nanoparticle albumin-bound (nab)-paclitaxel (nab-paclitaxel). For 43 patients who com-IP: 14.98.160.66 On: Fri, 13 May 2022 09:27:55 pleted nab-paclitaxel treatment, the compliance rate was 100%, without interruption or delay of nab-paclitaxel Copyright: American Scientific Publishers Delivered by Ingenta treatment. Dose reduction was necessary in 2 patients (4.6%) due to peripheral neuropathy. Thus, 98.6% of the planned doses were administered. As expected, the adjusted adjuvant regimen was safe and well toler-ated. Therefore wT x 12-* AC x 4 treatment procedure may be considered for breast cancer patients during COVID-19 pandemic.
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Background: The COVID-19 pandemic has influenced treatment decisions in cancer patients. There is increasing evidence that not all oncology patients are at increased risk of COVID-19 infection or death. This study aimed to look at rate of SARS-CoV-2 infection and mortality in patients with skin malignancies receiving systemic anti-cancer therapy (SACT) during the pandemic in Guy's Cancer Centre. Methods: All patients with skin cancer receiving SACT at Guy's Cancer Centre between March 1st and May 31st 2020 were included. Demographic data: sex, age, socio-economic status (SES), ethnicity, comorbidities, medications and smoking history were collected along with cancer characteristics: cancer type, stage, treatment paradigm, modality and line. COVID-19 infection was confirmed by PCR and severity defined by the World Health Organisation classification. Patients with radiological or clinical diagnoses alone were excluded. Results: Of 116 skin cancer patients on SACT over the 3-month period, 89% had Melanoma, 5% Kaposi's Sarcoma (KS), 3% Squamous Cell, 2% Merkel Cell, 1% Basal Cell Carcinoma and 1% Angiosarcoma. 53% were male and 78% were of low SES. 62% were being treated with palliative intent and 70% of these were on first line palliative treatment. The median age was 57.6 years in COVID-19 positive patients (n=3) compared to 60.3 years in the negative group (n=113). 58.6% received immunotherapy, 28.4% targeted therapy, 7.8% chemotherapy and 4.3% combined treatment. Of the 3 patients (2.6%) with confirmed COVID-19 infection, the two patients with KS were receiving liposomal doxorubicin hydrochloride and the other paclitaxel chemotherapy and the patient with Melanoma was receiving encorafenib and binimetinib. All COVID-19 positive patients were of low SES, 2 females and 1 male. There was a low rate of co-morbidities with hypertension in 1 COVID-19 positive patient and none in the negative group. All 3 confirmed COVID-19 patients developed severe pneumonia and were diagnosed within 7 days of the onset of symptoms. There were no COVID related deaths and one disease-related death in the negative cohort. Conclusion: There was a low rate of COVID-19 infection in the 116 skin cancer patients on SACT (2.6%) with 60% of patients on immunotherapy. All 3 confirmed cases had severe pneumonia with no COVID-19 related deaths (0%);2 were receiving chemotherapy and 1 on targeted therapy. Patients on treatment were encouraged to shield between hospital attendances during this period which may account for the reduced rate of SARS-CoV-2 infection. This data supports the emerging observations that immunotherapy does not confer an increased risk of severe COVID-19 infection in cancer patients. This observation is confounded by the relatively young age and low co-morbidity rates in the cohort which may have contributed to the low infection and mortality rate.
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Background: For cancer patients' treatment, coronavirus disease 2019 (COVID-19) poses a great challenge. COVID-19 presents as a severe respiratory infection in aging individuals, including patients with lung cancer. COVID-19 may be linked to the progression of aggressive lung cancer. Conversely, chemotherapy's side effects, such as chemotherapy resistance, acceleration of cellular senescence, could worsen COVID-19. Considering the above-mentioned facts, our present work was aimed to investigate the role of paclitaxel (a chemotherapy drug) in cell proliferation, apoptosis, and cellular senescence of gefitinib-resistant NSCLC cells (PC9-MET) and reveal the underlying mechanisms. Methods: PC9-MET cells were treated with paclitaxel for 72 h and then evaluated by cell viability assay, DAPI staining, Giemsa staining, apoptosis assay, ROS assay, SA-ß-Gal staining, TUNEL assay and western blotting. Results: Our results revealed that paclitaxel significantly reduced the viability of PC9-MET cells and induced morphological signs of apoptosis. The apoptotic effects of paclitaxel were observed by increased levels of cleaved caspase-3, cleaved caspase-9 and cleaved PARP. Additionally, paclitaxel increased ROS production, leading to DNA damage. Importantly, paclitaxel eliminated cellular senescence, which was observed by SA-ß-Gal staining. Conclusion: In light of these findings, paclitaxel could be a promising anticancer drug and could offer a new therapeutic strategy for gefitinib-resistant non-small cell lung cancer (NSCLC) during the COVID-19 pandemic.
ABSTRACT
Background: Platinum agents induce DNA crosslinking and cause accumulation of genotoxic stress, which leads to immune activation via IFN-γ signaling, making the combination with nivolumab (PD-1 antibody) an attractive strategy to enhance the benefit of either agent alone in metastatic triple-negative breast cancer (mTNBC). Methods: In this phase II open-label, investigator-initiated, multicenter trial, patients with unresectable locally advanced or mTNBC treated with 0-1 prior lines of chemotherapy in the metastatic setting were randomized 1:1 to carboplatin (AUC 6) with or without nivolumab (360 mg) IV every 3 weeks. Stratification factors included: germline BRCA (gBRCA) status, prior neo/adjuvant platinum, and number of prior lines of metastatic therapy. After approval of PD-L1 inhibition for mTNBC, the study was amended to include first-line mTNBC only and PD-L1 status was added as a stratification factor. Patients randomized to carboplatin alone were allowed to crossover at progression to receive nivolumab (+ nab-paclitaxel post-amendment). The primary objective was to compare progression-free survival (PFS) per RECIST 1.1 criteria of carboplatin with or without nivolumab in first-line mTNBC in the S intent-to-treat (ITT) population. Key secondary objectives were objective response rate (ORR), overall survival (OS), clinical benefit rate, and duration and time to objective response. PD-L1 status was confirmed centrally using the SP142 Ventana assay (positive, ≥1% IC). Paired researchbiopsies at baseline, on-treatment and at progression were performed, if safely accessible. The trial closed to accrual prior to reaching target accrual due to approval of PD-1 inhibition in combination with platinum-based chemotherapy for PD-L1+ mTNBC. Results: Between 1/30/2018 and 12/9/2020, 78 patients enrolled. Three patients did not receive protocol treatment, and the safety analysis was conducted among the 75 that received any treatment;37 received carboplatin + nivolumab (Arm A), 38 received carboplatin alone (Arm B). Median age was 59.1 yrs (range: 25.4-75.8). Four patients (5.3%) had a known gBRCA1/2 mutation. Sixty-two (82.7%) patients received 0 prior lines (ITT population) and 13 (17.3%) 1 prior line of metastatic therapy. Sixty-seven patients (89.3%) experienced any grade ≥2 treatment-related adverse event (AE). The most frequent AE were platelet count decrease (n=40;53.3%), anemia (n=36;48.0%), neutrophil count decrease (n=33;44.0%) and fatigue (n=24;32.0%). Grade 3/4 AE were observed in 46 (61.3%) patients, and there was one grade 5 AE (COVID19 pneumonia). Any grade ≥2 immune-related AE (irAE) were observed in 25 of the 37 (67.6%) patients treated with carboplatin + nivolumab. Grade 3/4 irAE were observed in 11 (29.7%) patients. In the ITT population (32 on Arm A;30 on Arm B), median PFS was 4.2 months with carboplatin + nivolumab, and 5.5 months with carboplatin (stratified HR 0.98, 95% CI [0.51-1.88];p=0.95). ORR was 25% vs. 23.3%, respectively. At a median follow-up of 23.5 months, median OS was 17.5 months vs. 10.7 months (stratified HR 0.63, 95% CI [0.32-1.24];p=0.18). In patients with PD-L1+ mTNBC (13 on Arm A;11 on Arm B), median PFS was 8.3 months and 4.7 months, respectively (stratified HR 0.63, 95% CI [0.21-1.89];p=0.41). ORR was 23.1% vs. 27.3%, respectively. Median OS was 17.5 months vs. 9.6 months (stratified HR 0.59, 95% CI [0.20-1.75];p=0.34). Conclusions: Addition of nivolumab to carboplatin in patients with previously untreated mTNBC, unselected by PD-L1 status, did not significantly improve PFS. A trend toward improved PFS and OS was observed in patients with PD-L1+ mTNBC. Tissue, blood and intestinal microbiome biomarker analyses are planned;bulk tumor and single-cell sequencing, and TCR sequencing in peripheral blood are ongoing.
ABSTRACT
Amplification and/or overexpression of HER2 in breast cancer (BCa) patients is associated with aggressive disease and poor prognosis. Herceptin® (trastuzumab), a monoclonal antibody targeting HER2, has an established role in the treatment of HER2 positive BCa. Addition of trastuzumab to anthracycline-and taxane-based neoadjuvant treatment in women with HER2-positive BCa has resulted in improvements in pathological complete response (pCR, a strong predictor for long-term clinical outcome), event-free survival (EFS) and overall survival (OS). This study is designed to compare efficacy (pCR) and safety between the originator Herceptin and the proposed trastuzumab biosimilar EG12014. The study is conducted during the COVID-19 pandemic (last patient in: March 2020, last patient last visit: planned Jan 2022) in Belarus, Chile, Colombia, Georgia, India, Russia, South Africa, South Korea, Taiwan, and the Ukraine. Methods: Neoadjuvant phase: 807 patients were randomized (1:1) into 2 arms receiving epirubicin (90 mg/m 2) and cyclophosphamide (600 mg/m2) every 3 weeks for 4 cycles, followed by EG12014 (arm 1) or Herceptin (arm 2) (both at loading dose: 8 mg/kg and maintenance dose: 6 mg/kg) and paclitaxel (175 mg/m2) every 3 weeks Sfor 4 cycles. Subsequently, the patients underwent surgery, and primary endpoint (pCR [ypT0/is ypN0]) was assessed. Adjuvant phase: After surgery, the patients received EG12014 or Herceptin (both at loading dose: 8 mg/kg and maintenance dose: 6 mg/kg) to complete 12 months of overall trastuzumab treatment. COVID-19 infections in the study population were not expected to affect primary endpoint analysis;thus, no sensitivity analysis was performed regarding COVID-19 status (symptomatic/asymptomatic). Differences between the 2 arms regarding delays in study treatments and procedures due to COVID-19 were assessed. Results (at interim data base lock, blinded as study is ongoing): Study population: the mean age was 50 years, the majority were white Europeans with tumor stage II, estrogen receptor positive and progesterone receptor negative. The median time from date of first diagnosis was 0.5 months. Primary endpoint pCR (ypT0/is ypN0) was reached with relative risk ratio (RR) for the full analysis set: 0.992 (90% CI 0.880 to 1.118) between the 2 treatment arms. Secondary pCR endpoints (defined as ypT0 ypN0 and ypT0/is) were also reached, with RR between the treatment arms: 0.917 and 0.992, respectively. Objective clinical response prior to surgery was similar for the 2 treatment arms: 83.8% and 83.6%, respectively. EFS, OS, safety endpoints (e.g., adverse events [most frequently reported: alopecia], serious adverse events, and deaths), and toxicity assessments, supported similarity between EG12014 and Herceptin. Sixty-two patients (7.7%) were infected with COVID-19;the infections were equally distributed between the 2 treatment arms. COVID-19 did not cause any discontinuations or deaths in the study. Among all reported COVID-19 events, 13 (21%) were asymptomatic, 11 (18%) were graded as 3 (severe), and 1 (1.6%) was graded as grade 4 (life threatening). Conclusion: EG12014 has shown equivalent efficacy to Herceptin in regard to clinical response (pCR) and has also demonstrated a similar safety profile. The impact of the COVID-19 pandemic has been comparable between the two treatment arms. The influence of the pandemic on this clinical study has been relatively low considering timing and the participating countries.