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Introduction: Croatian National Cancer Registry of Croatian Institute for Public Health reported that in year 2020 lung cancer was the second most common cancer site diagnosed in men with 16% and the third most common in women with 10% incidence among all cancer sites. Unfortunatelly lung cancer has the highest mortality in both men and women. Haematological malignancies had 7% share in all malignancies in both male and female cances cases. In 2020 190 newly diagnosed cases of lymphatic leukemia in men and 128 cases in women were reporeted, meaning 1.5 and 1.2% of all malignancies, respectively. Chronic lymphatic leukemia (CLL) is an advanced age disease and incidence increases with age. Impaired immunity, T and B cell dysfunction in CLL, chromosomal aberations, long-term immunosuppressive therapy and genetic factors can all cause secondary malignancies. Co- occurence of solid tumors and CLL is very rare. Although patiens with CLL have an increased risk of developing second primary malignancies including lung carcinoma, the data about their clinical outcomes are lacking. Parekh et al. retrospectively analyzed patients with simultaneous CLL and lung carcinoma over a 20-year period, and they found that ~2% of patients with CLL actually developed lung carcinoma. The authors claimed that up to 38% of patients will also develop a third neoplasm more likely of the skin (melanoma and basal cell carcinoma), larynx (laryngeal carcinoma) or colon. Currently there are no specific guidelines for concurrent CLL and non-small cell lung carcinoma (NSCLC) treatment. Usually, when the tumors are diagnosed simultaneously, treatment is based to target the most aggressive malignancy, as the clinical outcomes depend on the response of the tumor with the poorest prognosis. For this reason, a multidisciplinary approach is mandatory. Case report: A patient with history of coronary heart disease, myocardial infarction and paroxysmal atrial fibrillation was diagnosed in 2019 (at the age of 71) with B chronic lymphocytic leukemia with bulky tumor (inguinal lymph nodes 8x5 cm), stage B according to Binet, intermediate risk. He was treated with 6 cycles of chemoimmunotherapy (rituximab/cyclofosfamid/fludarabine). In 10/2019 remission was confirmed, but MSCT described tumor in the posterior segment of upper right lung lobe measuring 20x17 mm and bilateral metastases up to 11 mm. Bronchoscopy and biopsy were performed, and EGFR neg, ALK neg, ROS 1 neg, PD-L1>50% adenocarcinoma was confirmed. He was referred to Clinical Hospital Center Osijek where monotherapy with pembrolizumab in a standard dose of 200 mg intravenously was started in 01/2020. Partial remission was confirmed in October 2020. Immunotherapy was discontinued due to development of pneumonitis, dysphagia and severe weight loss (20kg), but without radiologically confirmed disease progression. At that time he was referred to our hospital for further treatment. Gastroscopy has shown erosive gastritis with active duodenal ulcus, Forrest III. Supportive therapy and proton pump inhibitor were introduced. After complete regression of pneumonitis, improvement of general condition and resolution of dysphagia, no signs of lung cancer progression were found and pembrolizumab was reintroduced in 12/2021. Hypothyroidism was diagnosed in 01/2021 and levothyroxine replacement ther apy was started. In 03/2021 he underwent surgical removal of basal cell carcinoma of skin on the right temporal region with lobe reconstruction. From 02/2021, when pembrolizumab was reintroduced, regression in tumor size was continously confirmed with complete recovery of general condition. He was hospitalized for COVID 19 infection in 09/2021, and due to complications pembrolizumab was discontinued till 11/2021. Lung cancer immunotherapy proceeded till 11/2022, when Multidisciplinary team decided to finish pembrolizumab because of CLL relapse. CLL was in remission till August 2022 when due to B symptoms, lymphcytosis, anemia and generalized lymphadenopathy, hematological workup including biopsy of cervical lymph node was performed and CLL/SLL relapse was confirmed. Initially chlorambucil was introduced, but disease was refractory. Based on cytogenetic test results (IGHV unmutated, negative TP53) and due to cardiovascular comorbidity (contraindication for BTK inhibitors) venetoclax and rituximab were started in 01/2023. After just 1 cycle of treatment normal blood count as well as regression of B symptoms and peripheral lymphadenopathy occured, indicating the probability of complete disease remission. In our patient with metastatic lung adenocarcinoma excellent disease control is achieved during 41 month of treatment in first line setting. Furthermore, relapsed/refractory CLL/SLL is currently in confirmed remission. Conclusion(s): Successful treatment of patients with multiple primary malignancies is based on multidisciplinarity, early recognition and management of side effects, treatment of comorbidities with the aim of prolonging life, controlling symptoms of disease and preserving quality of life.
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Background & Aim: Immune checkpoint inhibitors (ICI) revolutionized solid tumor treatment, however, in many tumors only partial response is achieved. Allocetra-OTS has an immune modulating effect on macrophages and dendritic cells and showed an excellent safety profile in patients including patients with sepsis and Covid-19. Here we investigated the anti-tumoral effect of Allocetra-OTS cellular therapy, in peritoneal solid tumor animal models. Methods, Results & Conclusion(s): Allocetra-OTS is manufactured from enriched mononuclear fractions and induced to undergo early apoptosis. Balb/c mice were inoculated intraperitoneally (IP) with AB12 (mesothelioma) with pLenti-PGK-V5-Luc-Neo and treated with anti- CTLA4 with or without Allocetra-OTS. Mice were monitored daily for clinical score and weekly using IVIS (Fig.1). Kaplan-Meier log rank test was done for survival. For Allocetra-OTS preparation, enriched mononuclear fractions were collected by leukapheresis from healthy eligible human donors and induced to undergo early apoptosis. Anti- CTLA4 standalone therapy significantly improved survival (Fig.2) from mean 34+/-9 to 44.9 +/-20 days. However, OTS standalone therapy was non-inferior and improved survival to 52.3 +/-20 days. Anti-CTLA4 + Allocetra-OTS combination therapy, ameliorated survival to 86.7+/-20 days with complete cancer remission in 60-100% of mice. Similar anti- tumoral effects of Allocetra-OTS were seen in mesothelioma model in a combination therapy with either anti-PD1 or cisplatin and using anti-PD1 in ID8 ovary cancer model. Based on single cell analysis confirmed by flow cytometry and pathology, the mechanism of action seems to be related or at least associated with an increase in f/480high peritoneal macrophages and a decrease in recruited macrophages, and to f/480high infiltration of the tumor. However, further studies are needed to confirm these observations. During IP tumor progression, Allocetra-OTS as a standalone therapy or in combination with ICI, or cisplatin, significantly reduced tumor size and resulted in complete remission in up to 100% treated mice. Similar results were obtained in ID8 ovary cancer. Based on excellent safety profile in > 50 patients treated in prior clinical trials for sepsis and Covid-19, Phase I/II clinical trial of Allocetra-OTS plus chemotherapy has started and three patient already recruited. A second phase I/II clinical trial of Allocetra- OTS plus anti-PD1, as a second- and third-line therapy in various cancers, was initiated in Q1 2023. [Figure presented]Copyright © 2023 International Society for Cell & Gene Therapy
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Introduction: Hepatocellular carcinoma (HCC) comprises the majority of primary liver cancer and has a poor prognosis. Clivus metastasis is rare with only a few reported cases in the medical literature. We report a case of a patient who presented with clival mass found to have metastatic HCC. Case Description/Methods: A 63-year-old woman presented for neurosurgical evaluation after she was found to have a skull base mass on computerized tomography (CT) of the head at an outside hospital. She endorsed dysphagia for three months, however denied headaches or visual disturbances. A magnetic resonance imaging (MRI) revealed a 5.4 cm by 2.9 cm by 3.6 cm mass in the clivus, which was deemed as the cause of dysphagia (Figure 1a). The patient subsequently underwent an endoscopic transsphenoidal resection of the clival mass. Histopathology from the tissue revealed a hepatoid carcinoma, concerning for metastatic HCC (Figure 1b and 2c). Immunohistochemical strains were positive for hepatocytic marker arginase-1 (Figure 1d). Laboratory studies revealed alpha fetoprotein (AFP) of 56,344 ng/mL, CA-125 of 376 ng/mL, normal B-HCG and carcinoembryonic antigen (CEA). Thereafter, a triple phase CT of the liver revealed two LI-RADS 5 lesions suggestive of HCC as the primary malignancy. Patient's case was discussed at multidisciplinary tumor board with recommendations for systemic immunotherapy with atezolimumab plus bevacizumab and radiation therapy to the clivus. Discussion(s): The incidence of HCC has almost tripled since the 1980s making it the fastest rising cause of cancer related deaths. Metastasis to the brain comprises 0.26% to 2.2% of cases and the skull base is the most rarely affected anatomical site. Although CNS presentation is rare, we may see more neurological manifestations of metastatic HCC with the persistence of chronic hepatitis infections, the rise of metabolic diseases such as NASH, and an increase in alcohol-related liver disease during the COVID-19 pandemic. Although exceedingly rare, metastasis to the clivus should be considered in the differential diagnosis of skull base masses. Despite detection and treatment, prognosis remains poor and emphasis should be placed on consistent HCC surveillance. This case emphasizes that skull masses must be evaluated diligently as they can be the first sign of underlying liver malignancy. Given the morbidity and mortality associated with HCC, recognition of atypical manifestations of HCC can lead to a prompt diagnosis and initiation of life-saving treatment. (Figure Presented).
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Purpose: The COVID-19 pandemic led to nationwide postponement of outpatient preventative health services. The purpose of our study was to determine the effect of the COVID-19 pandemic on hepatocellular carcinoma ultrasound (HCC US) surveillance volumes at a liver transplant center. Material(s) and Method(s): This retrospective study examined ultrasound volumes across the first two years of the pandemic (March 1, 2020, to February 28, 2022) compared to a baseline year (March 1, 2019, to February 28, 2020). Monthly and annual surveillance volumes, cumulative number of positive ultrasound examinations, and rate of follow-up CT or MRI on an US-3 observation were compared using paired t-tests. Result(s): A total of 6765 ultrasound examinations for HCC at our institution were performed over the three-year study period: 2507 in the baseline year, 1943 in the first year, and 2345 in the second year, representing a 24% (p = 0.036) and 6% (p = 0.144) decline in volume, respectively, compared to baseline. The first pandemic year had the greatest decline (mean 159/month, range 8-217, versus baseline year mean 209/month, range 182-241/month;p = .0363). The most dramatic reductions were in March, April, and May, in which 111, 8, and 126 surveillance ultrasound examinations were performed, respectively. In the baseline year, 95 (4%) had an US-3 observation (1 cm or larger nodule at ultrasound) and 63 (66%) underwent followup CT or MRI. In the first pandemic year, 64 (3%, p = 0.016) patients had an US-3 observation and 48 (75.00%, p = 0.0584) underwent follow-up CT or MRI. In the second pandemic year, 65 (3%, p = 0.001) patients had an US-3 observation and 48 (74%, p = 0.040) underwent follow-up CT or MRI. Conclusion(s): The significantly decreased surveillance ultrasound volume during the pandemic led to fewer positive surveillance studies and therefore fewer recommendations for follow-up imaging. As frequent surveillance is critical to HCC management, the pandemic is expected to have a significant impact on HCC epidemiology in the future.
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Ablation includes ethanol injection, radiofrequency ablation (RFA), microwave ablation (MWA), etc. Ablation can be potentially curative, minimally invasive and easily repeatable for recurrence. RFA has been the most widely used ablation technique for liver tumors. The new-generation MWA system incorporating antenna cooling and high-power generation has attracted attention. It can create a more predictable ablation zone and a larger ablation volume in a shorter procedure time. Many high-volume centers have introduced new-generation MWA in Japan. However, many studies failed to show that new-generation MWA is superior to RFA in terms of local control and overall survival. In MWA, clinical data have been insufficient compared with those of RFA. There has been keen competition between surgical resection and ablation for almost 40 years since the era of ethanol injection. In 2021, SURF trial revealed that overall survival and recurrence-free survival were not significantly different between surgical resection and RFA. SURF trial was a multicenter randomized controlled trial in which 49 major centers in Japan enrolled patients with good hepatic function (Child-Pugh scores <= 7) and primary HCC of largest diameter <= 3 cm, and <= 3 nodules during the 6-year period of 2009-2015. The registered patients were followed for at least 5 years. As the result of SURF trial and other comparative studies, the revised Japanese clinical practice guidelines in 2021 treats hepatic resection and ablation equally for patients with <= 3 lesions, <= 3 cm in diameter. Recently, the combination of systemic and locoregional therapies has been attracting much attention. Systemic therapy using molecular targeted agents or immune checkpoint inhibitors is used for advanced HCC which cannot be treated by surgery or ablation. On the other hand, some locoregional therapies, such as hepatectomy and ablation, are potentially curative, but they cannot be indicated for advanced HCC. Combination of both therapies is an approach to improve the prognosis of advanced HCC, which is not indicated for curative treatment. Systemic therapy is used to shrink the tumor, and then locoregional therapies are performed to eradicate it. The combination may build a new strategy for advanced HCC. Ablation is highly operator-dependent. The skills and outcomes are very different from operator to operator. Before the pandemic of COVID-19, we held domestic and international training programs for intermediate and advanced doctors and hands-on seminars for young doctors. These were activities to exchange knowledge and experience and standardize the procedure. During the pandemic, we cannot get together. Since August 2020, we have conducted Japan Ablation Webinar 8 times with a total of 1,566 participants. We have also conducted International Ablation Webinar 4 times with a total of 1,272 participated doctors. Education is important to acquire skills and knowledge for successful ablation. We have established Japan Academy of Tumor Ablation (JATA) this year. There are two triggers. One is that SURF trial revealed that there is no difference between hepatectomy and ablation. The other is that ablation for lung, bone and soft tissue and kidney cancers has become reimbursed with health insurance since this September.
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Introduction: There are eight SBD Clinics (symptomatic breast clinics) across the Republic of Ireland (plus Letterkenny satellite), where over 40,000 new patients are referred by their General Practitioner (GP) each year. Same day triple assessment clinics (TAC) worked well when the TACs were small, but with the current volumes it is not possible to image all patients same day. The first component of the triple assessment is clinical (E score). The E score dictates what imaging is required (E1 normal, E2 benign, E3 likely benign, E4 suspicious, E5 clinically breast cancer) and triages patients into urgent /non urgent and this became even more important in the COVID crisis. Despite the importance of the E score, there is very little in the literature about its accuracy. The aim of this study was to look at how good the E score is at indicating/not indicating cancer in a large volume SBD clinic in Dublin. Method(s): Single large centre SBD clinic in St James Hospital, Dublin. The study included the E score and cancer/not in all patients attending TAC clinic from 2018 to 2021. Data was collected prospectively and collated by database manager. Result(s): [Formula presented] Conclusion(s): This single centre study suggests that the E score is a reliable triage tool in a busy TAC clinic. As breast surgeons we need to establish a standard level of accuracy for clinical assessment in the TAC similar to that for the R (radiology ) score and B (biopsy) score.Copyright © 2023
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Introduction: Oncotype DX, a 21 gene assay has prognostic and chemotherapy predictive value. During COVID pandemic, guidance issued extended use of genomic testing to avoid chemotherapy to node positive patients. We aimed to identify impact of Oncotype DX testing in pre-operative setting of early breast cancer. Method(s): We retrospectively reviewed those patients where MDT recommended upfront Oncotype DX testing from 1st March 2020 till Sept 2022. Result(s): 59 patients were identified. The mean age was 55.7 +/- 11.4 years. Two-thirds were postmenopausal. Four-fifth had symptomatic presentation. the mean tumour size was 28.8 +/- 8.7 mm. Invasive ductal carcinoma was seen in 81% (N=48). Progesterone receptor positivity was seen in 93% (n=55). Node positivity was seen in 44% (n=26) while nodes were negative in 56% (n=33). Overall, low, intermediate and high score was seen in 47% (n=28), 8% (n=5) and 45% (n=26) respectively. In node negative patients, low, intermediate, and high score was seen in 45% (n=15), 10% (n=3) and 45% (n=15) respectively. Chemotherapy was avoided in 55% patients. In node positive patients, low, intermediate, and high score was seen in 50% (n=15), 8% (n=2) and 42% (n=11) respectively. Overall, chemotherapy was avoided in 23% patients with node positive disease. Conclusion(s): Upfront Oncotype DX testing can be used in node negative breast cancer patients. However, it should be used very cautiously in node positive women.Copyright © 2023
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Background The phase III CheckMate 816 study demonstrated statistically significant and clinically meaningful improvements in event-free survival (EFS) and pathologic complete response (pCR) with neoadjuvant N + C vs C in patients (pts) with resectable NSCLC. Here, we report 3-y efficacy, safety, and exploratory biomarker analyses from CheckMate 816. Methods Adults with stage IB (tumors >=4 cm)-IIIA (per AJCC 7th ed) resectable NSCLC, ECOG PS <= 1, and no known EGFR/ALK alterations were randomized to N 360 mg + C Q3W or C alone Q3W for 3 cycles followed by surgery. Primary endpoints were EFS and pCR, both per blinded independent review. Exploratory analyses included EFS by surgical approach and extent/completeness of resection, and EFS and pCR by a 4-gene (CD8A, CD274, STAT-1, LAG-3) inflammatory signature score derived from RNA sequencing of baseline (BL) tumor samples. Results At a median follow-up of 41.4 mo (database lock, Oct 14, 2022), continued EFS benefit was observed with N + C vs C (HR, 0.68;95% CI, 0.49-0.93);3-y EFS rates were 57% and 43%, respectively. N + C improved EFS vs C in pts who had surgery, regardless of surgical approach or extent of resection, and in pts with R0 resection (table). Recurrence occurred in 28% and 42% of pts who had surgery in the N + C (n = 149) and C arms (n = 135), respectively. In the N + C arm, BL 4-gene inflammatory signature scores were numerically higher in pts with pCR vs pts without, and EFS was improved in pts with high vs low scores (data to be presented). Grade 3-4 treatment-related and surgery-related adverse events occurred in 36% and 11% of pts in the N + C arm, respectively, vs 38% and 15% in the C arm. Conclusions Neoadjuvant N + C continues to provide long-term clinical benefit vs C in pts with resectable NSCLC, regardless of surgical approach or extent of resection. Exploratory analyses in pts treated with N + C suggested that high BL tumor inflammation may be associated with improved EFS and pCR. Clinical trial identification NCT02998528. Editorial acknowledgement Medical writing and editorial support for the development of this , under the direction of the authors, was provided by Adel Chowdhury, PharmD, Samantha Dwyer, PhD, and Michele Salernitano of Ashfield MedComms, an Inizio company, and funded by Bristol Myers Squibb. Legal entity responsible for the study Bristol Myers Squibb. Funding Bristol Myers Squibb. Disclosure P.M. Forde: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, F-Star, G1 Therapeutics, Genentech, Iteos, Janssen, Merck, Novartis, Sanofi, Surface;Financial Interests, Institutional, Research Grant: AstraZeneca, BioNTech, Bristol Myers Squibb, Corvus, Kyowa, Novartis, Regeneron;Financial Interests, Personal, Other, Trial steering committee member: AstraZeneca, BioNTech, Bristol Myers Squibb, Corvus;Non-Financial Interests, Personal, Member of the Board of Directors: Mesothelioma Applied Research Foundation;Non-Financial Interests, Personal, Advisory Role, Scientific advisory board member: LUNGevity Foundation. J. Spicer: Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb, CLS Therapeutics, Merck, Protalix Biotherapeutics, Roche;Financial Interests, Personal, Other, Consulting fees: Amgen, AstraZeneca, Bristol Myers Squibb, Merck, Novartis, Protalix Biotherapeutics, Regeneron, Roche, Xenetic Biosciences;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Bristol Myers Squibb, PeerView;Non-Financial Interests, Personal, Other, Data safety monitoring board member: Deutsche Forschungsgemeinschaft;Non-Financial Interests, Personal, Leadership Role, Industry chair: Canadian Association of Thoracic Surgeons. [Formula presented] N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi;Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer Ingelheim, Novartis, Sanofi, AbbVie, Amgen, Eli Lilly, Grunenthal, Tak da, Owkin;Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen;Financial Interests, Institutional, Funding: BMS;Non-Financial Interests, Personal, Officer, International Thymic malignancy interest group, president: ITMIG;Other, Personal, Other, Family member is an employee: AstraZeneca. M. Provencio: Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb, Janssen, Pfizer, Roche, Takeda;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Bristol Myers Squibb, MSD, Pfizer, Roche, Takeda. S. Lu: Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, GenomiCare, Hutchison MediPharma, Roche, Simcere, ZaiLab;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Hanosh, Roche. M. Awad: Financial Interests, Personal, Other, Consulting fees: ArcherDX, Ariad, AstraZeneca, Blueprint Medicine, Bristol Myers Squibb, EMD Serono, Genentech, Maverick, Merck, Mirati, Nektar, NextCure, Novartis, Syndax;Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb, Genentech, Eli Lilly. T. Mitsudomi: Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, BridgeBio Pharma;Financial Interests, Personal, Other, Consulting fees: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, MSD, Novartis, Ono, Pfizer;Financial Interests, Personal, Speaker's Bureau: Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, Guardant, Invitae, Merck, MSD, Novartis, Ono, Pfizer, Taiho;Financial Interests, Personal, Advisory Board: AstraZeneca;Non-Financial Interests, Personal, Leadership Role, Former president: IASLC. E. Felip: Financial Interests, Institutional, Research Grant: Fundacion Merck Salud, Merck KGAa;Financial Interests, Personal, Other, Consulting fees: Amgen, AstraZeneca, Bayer, BerGenBio, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffmann-La Roche, GlaxoSmithKline, Janssen, Merck, MSD, Novartis, Peptomyc, Pfizer, Sanofi, Takeda;Financial Interests, Personal, Speaker's Bureau: Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Janssen, Medical Trends, Medscape, Merck, MSD, PeerVoice, Pfizer, Sanofi, Takeda, touchONCOLOGY;Non-Financial Interests, Personal, Member of the Board of Directors: Grifols. S.J. Swanson: Financial Interests, Personal, Speaker's Bureau: Ethicon. F. Tanaka: Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, Chugai, Eli Lilly, Ono, Taiho;Financial Interests, Personal, Other, Consulting fees: AstraZeneca, Chugai, Ono;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Covidien, Eli Lilly, Intuitive, Johnson & Johnson, Kyowa Kirin, MSD, Olympus, Ono, Pfizer, Stryker, Taiho, Takeda. P. Tran: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. N. Hu: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. J. Cai: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb;Financial Interests, Personal, Other, Travel support for attending meetings and travel: Bristol Myers Squibb. J. Bushong: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. J. Neely: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. D. Balli: Financial Interests, Personal, Other, patents planned, issued, or pending: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. S.R. Broderick: Financial Interests, Personal, Advisory Board: AstraZeneca. All other authors have declared no conflicts of interest.Copyright © 2023 International Association for the Study of Lung Cancer. Published by E sevier Inc.
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Background: Residual disease (RD) following neoadjuvant chemotherapy (NAC) in early HER2- negative breast cancer (BC) remains an unmet medical need. However, no therapies to date have tested their activity directly in chemo-resistant RD. Here, we hypothesized that combining an oncolytic virus such as T-VEC with atezolizumab may offer clinical benefit in patients (pts) with RD after standard NAC. To our knowledge, PROMETEO is the first trial that examines the activity of immunotherapy in pts with RD prior to surgery. Method(s): PROMETEO (NCT03802604) is a singlearm, open-label, multicenter phase II trial. Women with triple-negative BC (TNBC) or hormone receptor-positive/HER2-negative (HR+/HER2-) BC with baseline (i.e., before NAC) ki67 >= 20% were eligible. RD was confirmed with a magnetic resonance imaging (MRI) showing a tumor diameter >= 10 mm and a core-biopsy detecting the presence of invasive cells. Before surgery, T-VEC was administered intratumorally on week 1 (106 pfu/mL), then in week 4 and every 2 weeks thereafter (108 pfu/mL) for 4 injections. Atezolizumab (840 mg) was administered intravenously every 2 weeks for 4 infusions, starting at week 4. Surgery was performed in < 3 weeks after completing the treatment. The primary objective was to evaluate the efficacy of the combination, measured by the rate of residual cancer burden (RCB) class 0/1 at surgery. Tumor samples collected at 5 timepoints (before NAC, during screening period, after first dose of T-VEC, after first dose of T-VEC and atezolizumab and at surgery) were mandatory to assess gene expression, tumor-infiltrating lymphocytes (TILs), immune cells PD-L1 IHC (SP142), tumor mutational burden (TMB) by FoundationOne and other translational endpoints. Result(s): Between Dec 2018 to Feb 2022, 28 pts were enrolled: 20 pts with HR+/HER2- disease and 8 pts with TNBC. Median age was 47 (range 31-71) and 71% of pts were premenopausal. At diagnosis before NAC, clinical stage II disease represented 60.7%, cN+ 60.7%, median Ki-67 was 37.5% (range 20%-95%), high TILs (>=10%) 37%, median TMB was 3 (0-19) and only 1 of 27 pts (3.7%) had a PD-L1-positive tumor. After NAC, mean tumor size by MRI was 28.3 mm (10-93). Two pts discontinued from the trial (1 withdrawal of consent and 1 COVID infection). The completion of 5 cycles of treatment was achieved by 73% of pts. The overall RCB-0/1 rate was 25% (7 of 28, 95% IC 10.7 - 44.9%), all with RCB 0 (pathologic complete response [pCR]). The pCR rate was 30% in HR+/HER2- disease and 12.5 % in TNBC. Radiological response by MRI was achieved by 3 of 28 pts (10.7%). Interestingly, none of the 7 pts with a pCR had radiological response (stable disease n=5, progressive disease [PD] n=2). Six pts (21.4%) had radiological PD and had RCB 2/3. Overall, 27 (96%) patients had at least one treatment-emergent adverse event (TEAE) of any grade. Most common grade 1 or 2 AEs were fever (11 pts, 39.3%), ALT increased (9 pts, 32.1%), AST increased (8 pts, 28.6%), arthralgia (6 pts, 21.4%) and anemia (6 pts, 21.4%). Grade 3 reversible neutropenia occurred in 1 patient. Across all pts, significant increases (p< 0.001) in TILs, immune genes and immune PDL1+ cells were observed after 1 dose of TVEC, 1 dose of the combination and at surgery. Intrinsic subtype changes at surgery occurred in 73.1% of cases, mostly (46.1%) Luminal A/B converting to Normal-like. At surgery, 19 of 26 (73.1%) of tumors were PDL1+. Conclusion(s): Two months of T-VEC in combination with atezolizumab induced a pCR in a subgroup of pts with chemoresistant HER2- breast cancer. This effect is probably related to the immune activation provoked by the combined treatment. Interestingly, a high discrepancy was observed between the presurgical radiological imaging and the actual surgical pathological report. Pre-operative window-ofopportunity trials in this context might provide important clues regarding the activity of novel treatment strategies.
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Introduction/Aims: This study investigated whether the Covid-19 pandemic affected lung cancer presentation, inparticular whether patients presented with later stage disease at diagnosis. Method(s): This retrospective cohort study analysed new primary lung cancers staged at Lung Cancer multi-disciplinary meeting in a tertiary referral centre. We compared cancer stage in a 6-month period before the Covid-19pandemic (Apr'19-Sept'19, Group 1) to a similar period following the start of the pandemic (Sept'20-Feb'21, Group2). Comparison of patient demographics, tumour staging and treatment referrals were made. Result(s): In Group 1, 91 new lung cancers were staged at the Lung Cancer MDT, with a median age of 68. 58% ofpatients were male. In Group 2, fewer patients (41) were staged, with a median age of 70, with the majority beingfemale (56%). 39% of those in Group 2 were current smokers versus 29.6% in Group 1. Median tumour size at timeof diagnosis was larger in Group 2 (5.6cm vs 4.1cm), reflecting overall upgrading from T3 to T4. Group 2 presentedwith higher stage nodal disease, where 36.5% of patients presented with N3 disease, versus 20.9% in Group 1. Bothgroups saw approximately 30% of patients with metastatic disease (M-stage) at time of presentation. Conclusion(s): This study suggests patients are presenting with more advanced disease following the pandemic, with larger tumours, and higher burden of nodal disease. The cause for this is likely multifactorial, and may include patient reluctance to present to doctors for review. Further study is required to explore factors such as patient education and lung cancer screening that may prevent this trend towards later presenting disease.
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Background: Mammographic screening programmes reduce breast cancer mortality, but detect many small tumours with favourable biological features which may not progress during a woman's lifetime. Screen-detected cancers are treated with standard surgery and adjuvant therapies, with associated morbidities. There is a need to reduce overtreatment of good prognosis tumours and numerous studies have evaluated the omission of radiotherapy in this context. However, there is little evidence to support surgical de-escalation, although percutaneous minimally invasive treatment approaches have been described. Vacuum-assisted excision (VAE) is in widespread use for management of benign lesions and lesions of uncertain malignant potential. SMALL (ISRCTN 12240119) is designed to determine the feasibility of using this approach for treatment of small invasive tumours detected within the UK NHS Breast Screening Programme (BSP). Method(s): SMALL is a phase III multicentre randomised trial comparing standard surgery with VAE for screendetected good prognosis cancers. The main eligibility criteria are age >=47 years, unifocal grade 1 tumours with maximum diameter 15mm, which are strongly ER/PR+ve and HER2-ve, with negative clinical/radiological axillary staging. Patients are randomised 2:1 in favour of VAE or surgery;with no axillary surgery in the VAE arm. Completeness of excision is assessed radiologically, and if excision is incomplete, patients undergo open surgery. Adjuvant radiotherapy and endocrine therapy are mandated in the VAE arm but may be omitted following surgery. Co-primary end-points are: 1. Noninferiority comparison of the requirement for a second procedure following excision 2. Single arm analysis of local recurrence (LR) at 5 years following VAE Recruitment of 800 patients will permit demonstration of 10% non-inferiority of VAE for requirement of a second procedure. This ensures sufficient patients for single arm analysis of LR rates, where expected LR free survival is 99% at 5 years, with an undesirable survival probability after VAE of 97%. To ensure that the trial as a whole only has 5% alpha, the significance level for each co-primary outcome is set at 2.5% with 90% power. The Data Monitoring Committee will monitor LR events to ensure these do not exceed 3% per year. Secondary outcome measures include time to ipsilateral recurrence, overall survival, complications, quality of life and health economic analysis. A novel feature of SMALL is the integration of a QuinteT Recruitment Intervention (QRI), which aims to optimise recruitment to the study. Recruitment challenges are identified by analysing recruiter/patient interviews and audiorecordings of trial discussions, and by review of trial screening logs, eligibility and recruitment data and study documentation. Solutions to address these are developed collaboratively, including individual/group recruiter feedback and recruitment tips documents. Result(s): SMALL opened in December 2019, but recruitment halted in 2020 for 5 months due to COVID-19. At 7st July 2022, 142 patients had been randomised from 26 centres, with a randomisation rate of approximately 45%, and a per site recruitment rate of 0.4-0.5 patients/month, approaching the feasibility recruitment target of 144 patients. Drawing from preliminary QRI findings and insights from patient representatives, a recruitment tips document has been circulated (on providing balanced information about treatments, encouraging recruiters to engage with patient preferences, and explaining randomisation). Individual recruiter feedback has commenced, with wider feedback delivered across sites via recruitment training workshops. Conclusion(s): Despite pandemic-related challenges, SMALL has an excellent recruitment rate to date and is expected to have a global impact on treatment of breast cancer within mammographic screening programmes.
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Introduction & Objectives: Urothelial cancer is a lethal disease with a rising incidence. The current imaging modalities for staging, either CT of the chest, abdomen and pelvis or FDG PET/CT, have issues. CT is known to have relatively low sensitivity for detecting low volume metastatic disease, while FDG PET is predominantly renally excreted and has intense activity in the urinary tract, which limits its utility to detect bladder or upper tract lesions, or nodal metastases in close proximity to the urinary tract. Utilizing 89Zr-TLX250, which is predominantly hepatically cleared, may improve imaging in these scenarios. The aim of this study is to explore the feasibility, safety, and utility of Zirconium-89-Girentuximab (89Zr-TLX250) PET/CT in the accurate staging of bladder and urothelial cancer as compared to FDG PET. Material(s) and Method(s): ZipUp is single-arm, phase I trial examining the feasibility, safety, and utility of 89Zr-TLX250 PET/CT in patients either undergoing pre-operative staging of urothelial carcinoma or bladder cancer for curative intent, or with known metastatic urothelial carcinoma or bladder cancer. Following Ethical approval (HREC ID: RGS3940), all participants undergo 89Zr-TLX250 PET/CT and will need to have undergone recent FDG PET/CT for means of comparison (Figure 1. Trial Schema). This trial aims to recruit 10 participants undergoing pre-operative staging prior to planned cystectomy and 10 participants with known metastatic disease. The primary endpoint is feasibility defined by the ability to recruit to the target sample size within the study duration. Secondary endpoints are safety, tolerability and sensitivity/specificity in detecting lymph node metastases (pre-cystectomy group) compared with FDG PET/CT. Result(s): Since May 2021, 15 patients consented to participate, but 2 patients subsequently withdrew. 7 patients did not proceed to dose administration and imaging due to COVID-19 pandemic related supply issues of IMP which would have delayed initiation of treatment. 6 patients have been enrolled with imaging performed. . 5 pre-cystectomy staging group . 1 metastatic group Conclusion(s): If 89Zr-TLX250 PET/CT is proven to be feasible, safe, and effective in staging urothelial cancer, it could improve the appropriate selection of treatment for patients with metastatic or primary urothelial carcinoma or bladder cancer. [Figure presented]Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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Background: The COVID-19 pandemic had a significant impact on the healthcare system globally, including oncology. Which, in turn, led to significant delays in diagnostic and therapeutic procedures. This work aims to evaluate COVID-19 impact on the treatment of bone sarcoma in adult patients based on experience in a single, high-volume institution. Method(s): We have analyzed the early local outcomes (i.e., the possibility of limb-sparing surgery) in all patients with primary bone tumours treated between 2016-01-28 and 2022-11-07 in Polish main sarcoma reference center. Patients treated in the 2016-2019 period were labelled as a "pre-pandemic" group, and patients treated in the 2020-2022 - "pandemic". Mann-Whitney U and Chi-square tests were used in the statistical analysis. Result(s): There were 302 eligible patients identified. The group characteristics are presented in the table. There were no differences in patient-related variables and histological subtypes of tumours between the two groups. The tumour size did not differ (p = 0.053), when all tumour grades were considered, but high-grade tumours were larger in the "pandemic" group (p = 0.034). This was reflected in the percentage of limb-sparing surgeries which dropped from 83.3% to 68.2% ("pre-pandemic" vs "pandemic", p = 0.004). This difference was even more evident in the case of high-grade tumors - 78% vs. 54%, respectively (p = 0.001). [Formula presented] Conclusion(s): To our knowledge, this is the first report of the long-lasting detrimental impact of the COVID-19 pandemic on oncologic treatment outcomes in adult patients with primary malignant bone tumors. Legal entity responsible for the study: The authors. Funding(s): Has not received any funding. Disclosure: All authors have declared no conflicts of interest.Copyright © 2023 European Society for Medical Oncology
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Princess Margaret Cancer Centre (PM) receives roughly 120 new patients (pts) per year with uveal melanoma (UM). Moderate to high-risk pts, based on AJCC staging and cytogenetics, undergo a strict surveillance program for metastases with liver MRI every 4-6 months and annual chest imaging. The importance of surveillance has been highlighted by new therapies which are likely more effective in pts with lower volume metastases. In this single center retrospective study, we assessed the effectiveness of a virtual surveillance model, by comparing UM pts on standard in-person surveillance (SS) pre-COVID (August 2018 to March 2020) with virtual surveillance (VS) after COVID onset (April 2020 to November 2021). Virtual visits were done through phone or MS Teams video calls, and images were done either locally or externally. We identified 106 pts who underwent SS and 107 pts who underwent VS. In the SS group, 10 pts were diagnosed with metastasis and of these 9 (90%) were staged as M1a disease and 1 (10%) was M1b. In the VS group, 20 pts were diagnosed with metastases, 2 (10%) of which had M1b disease and 18 (90%) with M1a disease. Fifteen (14%) pts in the SS group and 34 (20%) pts in the VS group lived out of province;13 (12%) of the SS pts and 36 (21%) of pts in the VS cohort had scans externally. With regards to surveillance adherence in the SS group, 70 (66%) of pts had their scans performed on time versus 127 (75%) of pts in the VS cohort. Virtual screening of pts with moderate to high-risk UM during the COVID 19 pandemic showed similar ability to detect low volume disease compared with our standard screening. There was a higher level of adherence to screening during the VS period. When implemented appropriately, VS appears to be an effective model to monitor UM pts.
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Purpose: Locally advanced cervical cancer was defined by an international consensus panel as a high priority malignancy during the COVID-19 pandemic, recommending prompt initiation of definitive treatment and completion of treatment (PMID 32563593). The objective of this study was to study the clinical outcomes of patients (pts) with cervical cancer treated with definitive chemoradiation (CRT) and brachytherapy (BT) at our institution in 2019 (pre-COVID) and in 2020 (peri-COVID). Material(s) and Method(s): This was a retrospective cohort study of pts with FIGO Stage IB2-IVA cervical cancer at our institutions from 1/1/2019 to 12/31/2020. Pts received CRT followed by intracavitary brachytherapy (IC) with two operative insertions one week apart, or interstitial (IS) BT with one operative insertion. BT treatment was planned using image-guided CT or MR delineation. Pre-COVID was defined by initiation of CRT in 1/2019-12/2019, and peri-COVID was defined by initiation in 1/2020-10/2020. Process changes peri-COVID included limited on-site staff (e.g., minimal OR staff, no trainees, remote physics team), universal implementation of COVID-19 testing prior to surgery, and CT instead of MR-delineation based treatment. Outcomes of interest were time to treatment initiation and completion and differences in treatment planning modality or dosimetry. Fisher's exact and Mann Whitney U tests were used with significance p<0.05. Result(s): Thirty-one pts were included, with 18 patients undergoing treatment pre-COVID and 13 peri-COVID. The median age at diagnosis pre-COVID was 57.7 (range 23-77) and for peri-COVID, 45.5 (range 28-62, p=0.06). There were no differences in non-English speaking pts (44% vs 59%, p=0.71) or uninsured pts (11% vs 33%, p=0.184) between the two cohorts. Median time to initiation of treatment from biopsy diagnosis was 52 days (range 13-209) in 2019 and for peri-COVID, 55.5 (range 20-173, p=0.71). During COVID, four pts had delayed initiation to treatment >100 days: two related to fertility, and one due to fear of COVID-19. For this pt, tumor size progressed from 2.3 cm to 4.2 cm maximal dimension. One pt treated in 2020 tested positive following treatment and did not require hospital admission. All pts except one completed CRT with RT: 25 pts pelvic RT (45 Gy), 3 pelvic and para-aortic RT (45 Gy with 57.5 Gy concomitant boost to nodes), 8 pts pelvic RT (45Gy) with sequential parametrial boost (50.4-59.4 Gy) using IMRT with no dose differences between pre and peri-COVID (Table 1). No pts required treatment breaks and the median overall treatment time was 50 days (range 31-85) in 2019 vs 50 days (range 43-63) in 2020 (p=0.710). Conclusion(s): Despite the significant burden of the COVID-19 pandemic on our health care system, all cervical cancer pts receiving CRT met standard of care including CRT and BT within the recommended time frame with no significant differences in dosimetric treatment parameters pre- and peri-COVID. Delays in treatment initiation of treatment initiation were seen in 30% of pts in the peri-COVID period, suggesting that patients may have had increased barriers to access care. More follow-up is needed to determine how the Covid pandemic impacted cervical cancer outcome measures. Copyright © 2022
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Objective: Coronavirus disease-2019 (COVID-19) pandemic changed various priorities in health area. Many elective surgeries for renal cell cancers (RCC) have been postponed. We examined the influence of the COVID-19 pandemic on the surgical treatment of RCC in Turkey. Material(s) and Method(s): Surgically treated 457 patients for kidney tumor, from March 1, 2019 to February 28, 2021 in 9 centers in Turkey were analyzed retrospectively. Result(s): The number of surgical treatments for RCC during the COVID-19 pandemic has decreased significantly, in contrast to the same period before COVID-19. Admission symptoms were similar in these two periods (p=0.32). However, although not statistically significant, the rate of admission to hospital due to hematuria was higher during the pandemic period compared to the prepandemic period (14.4% vs 9.8%, respectively). The two study periods differed significantly in terms of the rate of metastatic RCC detected in preoperative imaging (13.1% vs 6.1%, during COVID-19 and pre-COVID-19, respectively) (p=0.01). Moreover, the study periods differed significantly in terms of time between imaging and operation [35 (2-240) vs 30 (1-210) days, during COVID-19 and pre-COVID-19, respectively] (p=0.01). However, these two periods were similar in terms of tumor size, type of surgery, and pathological stage (p>=0.05). Although the pathological stages were similar among the groups, nephrectomies due to the metastatic disease were significantly higher in the pandemic period (p=0.01). Conclusion(s): The number of RCC-related surgeries were significantly decreased during the pandemic period. However, the rate of surgery for metastatic disease has significantly increased. © Copyright 2022 by Urooncology Association Bulletin of Urooncology / Published by Galenos Yayinevi 119.
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Purpose: We aimed to evaluate the role of plasma fibrinogen and D-dimer as prognostic biomarkers in patients with non-muscle-invasive bladder cancer (NMIBC). Method(s): A prospective study that included 35 patients (30 males) with newly diagnosed NMIBC who underwent complete transurethral resection between September 2020 and December 2021. Patients with history of thromboembolic event or anticoagulant intake or active infection, patients with deranged hepatorenal functions, inflammatory bowel disease, refractory hypertension, or diagnosed with Covid-19 infection within 1 month before surgery or routine follow-up were excluded. Follow-up was done as per NCCN guidelines. Fibrinogen and D-dimer levels were measured within 7 days of surgery or follow-up and analyzed for recurrence-free survival (RFS) and progression-free survival (PFS). Cox regression analyses were adopted to assess the influence of these two parameters on RFS and PFS. Result(s): The mean age was 53.9 years with a median follow-up of 9 months. The cut-off values of fibrinogen and D-dimer were 402.5 mg/dl and 0.55 mug/ml, respectively. Kaplan-Meier analysis demonstrated that high fibrinogen and D-dimer levels were significantly related to poor RFS (p < 0.001) and PFS (p < 0.001). On multivariate analysis, only fibrinogen and D-dimer retained their significance for RFS (p = 0.026 and 0.014, respectively) and PFS (p = 0.027 and 0.042, respectively) but not tumor size. High levels of fibrinogen and D-dimer were also present in patients who had recurrence or progression at follow-up visits compared to the rest of the patients. Conclusion(s): High levels of fibrinogen and D-dimer may indicate worse prognosis in patients with NMIBC, suggesting that these two can be used as prognostic biomarkers.
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Aim: The increased burden of care at different points in the healthcare system, due to the COVID 19 pandemic, has led to a delay in diagnosis and treatment in patients with colon cancer, presenting with more advanced disease than patients before the pandemic. The objetive is to test differences in how advanced the disease is in patients with colon cancer, before and during the COVID 19 pandemic. Method(s): Retrospective study in third level hospital, where patients who underwent scheduled surgery for colon cancer were included, dividing them into two groups, pre-Covid group (July 2019-February 2020) and post-Covid group (July 2020-February 2021). We analyzed demographic data, TNM staging, and complications in the immediate postoperative period. Result(s): Data from 172 patients (n = 172), mean age 72 years, 124 males (72.1%) and 48 females (27.9%). We included 82 patients (47.7%) in the pre-Covid group and 90 patients (52.3%) in the post-Covid group. The results obtained were, regarding post-surgical stay, the long stay ( > 7 days) was in preCovid period 46.3% vs postCovid 62.2% (P = 0.037). Regarding TNM staging, those patients with a T >=T4 have been in preCovid period 19.5% vs postCovid 42.2% (P = 0.001), with a stage >=IIa has been preCovid vs postCovid of 70.7% vs 88.9% (P = 0.003), and those with an N > N0 have been preCovid 41.5% vs postCovid 57.8% (P = 0.033). Conclusion(s): The delay in health care, due to the COVID 19 pandemic, has caused in patients operated on for colon cancer a greater progression of the disease in relation to those patients operated on before the pandemic, being striking the greater tumor size as well as the local invasion of the same. Likewise, we have identified an increase in prolonged admissions after surgery.
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INTRODUCTION: Head and neck exocrine gland tumors metastases to central nervous system (CNS) account for less than 1% with median survival of less than 6 months. Unlike brain metastases from lung, breast, melanoma, and colon, there is no established consensus or published clinical guidelines in the management from excorine glands. Filipino patients are manage individually but experienced delays due to limited access to a tertiary level health care and with scarcity of treatment protocols. Methods and RESULTS: We present two cases with exocrine glands carcinoma with CNS metastases. First case is a 51/F with a known case of left parotid cystic adenocarcinoma s/p parotidectomy and radiation therapy 2 years prior to the development of neurological deficits and COVID-19 infection, neuroimaging noted extra-axial 7.5 x 5 x 4.5 cm contrast enhancing tumor at bilateral frontal convexity. She underwent bifrontal craniotomy, gross total excision of tumor and anterior sagittal sinus, histopathology results cystic adenocarcinoma. She was discharged GOS 2, planned for chemoradiotherapy but lost to follow up and expired after 2 months post op. Second case is a 28/M known case of lacrimal gland pleomorphic adenocarcinoma OD s/p excision biopsy 2 years prior to the development of multiple right frontal lobe, right orbital wall and right pterion metastases. He underwent gross excision of extracranial and intracranial tumors and a right orbital exenteration. He was discharged GOS 2 and underwent chemoradiation as outpatient with good tumor control and no tumor recurrence after 1 year of treatment. DISCUSSION: CNS metastases from exocrine glands are rare and difficult to manage since no approved protocol was established. Patients in low resource setting were then manage on individual basis since molecular and genomic studies are not available. The delays in the management are multifactorial such as geographic disadvantages, COVID-19 pandemic, and government's inadequate support for health system.
ABSTRACT
Background: Dacomitinib is a second generation EGFR tyrosine kinase inhibitor approved as first-line therapy in advanced EGFR mutated NSCLC. In the phase 3 ARCHER 1050 trial, PFS and OS were improved with dacomitinib compared to gefitinib. However, patients (pts) with central nervous system (CNS) metastases (mets) were ineligible to enroll into the study. ATORG-003 is an ongoing investigator-initiated single-arm phase 2 trial evaluating a dose titration strategy to improve the safety and tolerability of dacomitinib whilst maintaining efficacy. The intracranial activity of dacomitinib was evaluated in a prespecified subgroup analysis. Method(s): ATORG-003 (9 sites, 5 Asian countries) is enrolling newly diagnosed stage IIIB-IV NSCLC pts with EGFR mutations (exon 19 deletion [ex19del] or L858R). Pts receive dacomitinib 30 mg orally once daily for one cycle (4 weeks [wks]), after which pts with grade <=1 toxicity may escalate to 45 mg once daily (investigator/pt decision). A 24 pt subgroup with asymptomatic/controlled CNS mets completed enrollment in Jun2021. CNS mets were assessed by MRI scan at baseline and every 8 wks for 18 months (mo), then every 12 wks with MRI/CT. Key study secondary endpoints include intracranial objective response rate (iORR) and intracranial progression free survival (iPFS). Analyses were based on 7Jun2022 data cutoff date (median 18.7 mo follow-up). Result(s): Of 24 pts with CNS mets, median age was 65 years (range 33-78), ECOG PS 0/1 in 17%/83% and ex19del/L858R/both in 50%/46%/4%. 8/24 (33%) pts had prior intracranial radiotherapy. 2/24 pts dose escalated to 45 mg once daily after Cycle 1. There was measurable (>=10 mm target lesion) CNS mets in 9/24 (38%) pts. The iORR was 67% (1 intracranial CR [iCR], 5 intracranial PR), and median intracranial duration of response (iDoR) was not reached (NR). In 14 pts with non-measurable CNS mets only, iCR was seen in 6 (43%) pts. Median iPFS was NR with only n=5 CNS progression events in the entire cohort and n=7 remain on treatment. Overall (intra and extracranial) ORR was 67% and PFS rate at 12 mo was 42%. Conclusion(s): Dacomitinib has significant intracranial activity with observed durable responses in advanced EGFR mutated NSCLC with CNS mets. Clinical trial identification: NCT04027647. Legal entity responsible for the study: Asian Thoracic Oncology Research Group (ATORG). Funding(s): Pfizer. Disclosure: A. Tan: Financial Interests, Personal, Advisory Board: Amgen, Pfizer, Bayer. D. Kim: Financial Interests, Institutional, Principal Investigator: Alpha Biopharma, Amgen, Astrazeneca/Medimmune, Boehringer Ingelheim, BMS, Bridge BioTherapeutics, Chong Keun Dang, Daiichi-Sankyo, GSK, Hanmi, Janssen, Merck, Merus, Mirati Therapeutics, MSD, Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, Yuhan;Financial Interests, Institutional, Funding: InnoN, Asia Thoracic Oncology Research Group;Non-Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, BMS/ONO Pharmaceuticals, Daiichi-Sankyo, GSK, Janssen, Merck, MSD, Oncobix, Pfizer, SK Biopharm, Takeda;Financial Interests, Personal, Advisory Role: Scientific advisor for Health insurance review and assessment service, Korea;Non-Financial Interests, Personal, Leadership Role: Asian Thoracic Oncology Research Group, Korean Association for Lung Cancer, Korean Cancer Association, Korean Society of Medical Oncology. T. Baisamut (Reungwetwattana): Financial Interests, Personal, Advisory Board, and speaker: Astrazeneca, Pfizer, Roche, MSD, Novartis, BMS, Amgen;Financial Interests, Personal, Advisory Board: Yuhan;Financial Interests, Institutional, Invited Speaker: Astrazeneca, Roche, Novartis, MSD. L. Yueh Ni: Financial Interests, Personal, Other, Panel of Discussion for Hepatocellular Carcinoma: AstraZeneca;Financial Interests, Personal, Advisory Board, Advisory Board Meeting for early breast cancer management in our current practice.: Roche;Financial Interests, Personal and Institutional, Invited Speaker, Research Title: A multicentre, open-label, single-arm, lecular profiling study of patient with EGFR mutation-positive locally advanced or metastatic NSCLC treated with Osimertinib: AstraZeneca;Financial Interests, Personal and Institutional, Invited Speaker, Research Title: A Phase 3 Double-blinded, Two-arm Study to Evaluate the Safety and Efficacy of Pembrolizumab (MK-3475) versus Placebo as Adjuvant Therapy in Participants with Hepatocellular Carcinoma and Complete Radiological Response after Surgical Resection or Local Ablation (KEYNOTE-937): MSD;Financial Interests, Personal and Institutional, Invited Speaker, Research Title: A Phase III, Randomized, Double-blind Study to Assess the Efficacy and Safety of Lazertinib versus Gefitinib as the First-line Treatment in Patients with Epidermal Growth Factor Receptor Sensitizing Mutation Positive, Locally Advanced or Metastatic Non-small Cell Lung Cancer: YUHAN;Financial Interests, Personal and Institutional, Invited Speaker, Research Title: A phase II randomized study of the combination of Ribociclib plus goserelin acetate with Hormonal Therapy versus physician choice chemotherapy in premenopausal or perimenopausal patients with hormone receptor-positive/HER2-negative inoperable locally advanced or metastatic breast cancer - RIGHT Choice Study: Novartis;Financial Interests, Personal and Institutional, Invited Speaker, Research Title: A Global, Randomized, Phase 3, Open-Label Study of REGN2810 (Anti-PD-1 Antibody) versus Platinum-Based Chemotherapy in First-Line Treatment of Patients with Advanced or Metastatic PD-L1+ Non-Small Cell Lung Cancer: Regeneron;Financial Interests, Personal and Institutional, Invited Speaker, Research Title: A Phase 3 study to Evaluate Zimberelimab (AB122) Monotherapy Compared to Standard Chemotherapy or Zimberelimab Combined with AB 154 in Front-Line, PD-L1 Positive, Locally Advanced or Metastatic Non-Small Cell Lung Cancer: Arcus;Financial Interests, Personal and Institutional, Invited Speaker, Research Title: A Prospective, Multicenter, Non-Interventional Genomic Profiling Study in Subjects with Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) using Foundation Medicine: Roche;Financial Interests, Personal and Institutional, Invited Speaker, Research Title: A Phase 3, randomize, double-blind trial of pembrolizumab (MK-3475) with or without lenvatinib (E7080/MK-7902) in participants with treatment naiv , metastatic non-small cell lung cancer (NSCLC) whose tumors have a tumor proportion score (TPS) greater than or equal to 1% (LEAP-007): MSD. G.F. Ho: Financial Interests, Personal, Advisory Board: Merck & Co., Inc., Novartis, AstraZeneca, Boehringer Ingelheim, Pfizer;Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Pfizer, Merck & Co., Inc., Novartis, Roche, Boehringer Ingelheim;Financial Interests, Personal, Other, Chairperson: Bristol Myers Squibb;Financial Interests, Institutional, Invited Speaker: EliLily, Regeneron, Merck & Co., Inc., AB Science, Astellas, Tessa Therapeutics, Roche, Arcus Bioscience, AstraZeneca, Pfizer;Non-Financial Interests, Institutional, Product Samples: Pfizer, Eli Lilly, Novartis, Janssen Pharmaceuticals. L.M. Tho: Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Roche, MSD, Pfizer. N. Prasongsook: Financial Interests, Personal, Advisory Board: Roche (Thailand), Novartis;Financial Interests, Personal, Invited Speaker: AstraZeneca. T.S.K. Mok: Financial Interests, Personal, Invited Speaker: AbbVie, ACEA Pharma, Alpha Biopharma, Amgen, Amoy Diagnostics, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Daiichi Sankyo, Fishawack Facilitate, InMed Medical Communication, Lunit USA, Inc., Merck Serono, MSD, Roche, MD Health, Medscape/WebMD, PeerVoice, Permanyer SL, Prime Oncology, Research to Practice, Touch Medical Media, Sanofi-Aventis, Takeda, PER, Daz Group, Janssen Pharmaceutical NV, Jiahui Holdings Co., LiangYiHui Healthcare, Lucence Health Inc., Merck Pharmaceuticals HK Ltd., MiRXES, Novartis, OrigiMed Co. Ltd., Pfizer, Shanghai BeBirds Translation & Consulting Co., Ltd., Taih harmaceutical Co., Ltd., AstraZeneca;Financial Interests, Personal, Advisory Board: AbbVie, ACEA Pharma, Alpha Biopharma, Amgen, Amoy Diagnostics, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Blueprint Medicines, Berry Oncology, CStone Pharma, Daiichi Sankyo, Fishawack Facilitate, Eisai, Gritstone Oncology, Guardant Health, G1 Therapeutics, Hengrui, Ignyta, IQVIA, Incyte Corporation, Inivata, Janssen, Loxo Oncology, Qiming Dev., Lunit USA, Inc., Merck Serono, MSD, Roche, Mirati Therapeutics, MoreHealth, Novartis, OrigiMed, Puma Tech., Sanofi-Aventis, Takeda, Virtus Medical, Yuhan, Curio Science, Bayer Healthcare Pharmaceuticals Ltd., Covidien LP, C4 Therapeutics, Cirina Ltd., Da Volterrra, F. Hoffmann-La Roche Ltd./Genentech, Gilead Sciences, Lucence Health Inc., Medscape LLC / WebMD, MiRXES, OSE Immunotherapeutics, Pfizer, SFJ Pharmaceutical Ltd., Synergy Research, Tigermed, Vertex Pharmaceuticals, Berry Oncology, D3 Bio Ltd., Lakeshore Biotech;Financial Interests, Personal, Officer, Chairman: ACT Genomics-Sanomics Group;Financial Interests, Personal, Invited Speaker, Former known as Hutchison Chi-Med: HutchMed;Financial Interests, Personal, Stocks/Shares: Sanomics Ltd., Biolidics Ltd., Aurora Tele-Oncology, AstraZeneca;Financial Interests, Personal, Stocks/Shares, Former known as Hutchison Chi-Med: HutchMed;Financial Interests, Institutional, Funding, For clinical trials performed at CUHK: AstraZeneca, BMS, Merck Serono, MSD, Novartis, Pfizer, Roche, SFJ Pharmaceuticals, XCovery, Takeda, G1 Therapeutics, Clovis Oncology;Non-Financial Interests, Personal, Advisory Role: geneDecode;Non-Financial Interests, Personal, Other, Invited Speaker: AstraZeneca, Aurora Tele-Oncology, Lunit USA, Inc., Sanomics Ltd.;Non-Financial Interests,Personal, Leadership Role, Term ended on 30 June 2022: American Society of Clinical Oncology (ASCO);Non-Financial Interests, Personal, Leadership Role: Asian Thoracic Oncology Research Group (ATORG), Chinese Lung Cancer Research Foundation Limited (CLCRF), Hong Kong Cancer Fund (HKCF), Hong Kong Cancer Therapy Society (HKCTS), St. Stephen's College & Prep. School (Hong Kong);Non-Financial Interests, Personal, Leadership Role, Term ended: Chinese Society of Clinical Oncology (CSCO);Non-Financial Interests, Personal, Leadership Role, Term ended on 30 April 2019: International Association for he Study of Lung Cancer (IASLC). D.S.W. Tan: Financial Interests, Personal, Invited Speaker: Merck, Pfizer, Novartis, Boehringer Ingelheim, Roche, Takeda;Financial Interests, Personal, Advisory Role: Novartis, Bayer, Boehringer Ingelheim, Celgene, AstraZeneca, Eli-Lilly, Loxo, GlaxoSmithKline, MSD;Financial Interests, Institutional, Funding: Novartis, AstraZeneca, Bayer, Pfizer, Amgen. H.H.F. Loong: Financial Interests, Institutional, Invited Speaker: Boehringer Ingelheim, MSD;Financial Interests, Personal, Invited Speaker: Eli-Lilly, Illumina, Bayer, Guardant Health;Financial Interests, Personal, Advisory Board: Novartis, Takeda. All other authors have declared no conflicts of interest. Copyright © 2022