Anaesthetic Management for A Patient Presenting for Caesarean Delivery with A giant Thymoma - A Case Report

Presentation of a thymoma during pregnancy means that safe delivery becomes more challenging. We present a 33-year-old pregnant woman who was diagnosed with a large thymoma causing marked compression of the tracheobronchial tree and right atrium. After various multidisciplinary meetings she presented for elective caesarean section delivery at 31 weeks of gestation. A combined spinal-epidural anaesthesia was performed, along with colloid pre-and co-loading, and vasopressor support. The delivery was uneventful. The possibility of catastrophic complications was foreseen. Therefore, all requirements for the possibility of airway or haemodynamic collapse were planned carefully, including the possibility of emergent cardiopulmonary bypass.Copyright © 2023, College of Anaesthesiologists of Sri Lanka. All rights reserved.

Deviation from standard cancer treatment during the first wave of the COVID-19 pandemic in India: A cross-sectional study

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.

Short Term Outcome of Management of Early Breast Cancer Patients in COVID-19 Era. Ain Shams University Experience

Introduction: COVID-19 implied that a great number of infected individuals were hospitalized and possibly admitted to intensive care units. Cancer centers have rapidly changed models of care by delaying non-urgent surgeries. Breast surgeries were delayed for early breast cancer patients forcing clinicians to potentially alter treatment recommendations by neoadjuvant chemotherapy until appropriate conditions were established. Aim of the work: to assess conservative breast cancer surgery after neo-adjuvant therapy in early breast cancer patients in COVID-19 era as regard surgical outcome, complications and early recurrence comparing results with previous results when patients underwent primary conservative breast surgery. Patients and Methods: This is a cohort study that was conducted 52 patients with early breast cancer stage I and II a. Patients were divided into two groups (A) and (B). Group A included 26 patients who underwent primary conservative breast surgery. Group B included 26 patients who underwent conservative breast surgery after neo-adjuvant therapy during COVID-19 era. Results: Intra-operative re-excision was done in 5 patients (19.2%) in group A and 3 patients (11.5%) in group B. Two patients (7.7%) in group A and 1 patient (3.8%) in group B were converted to modified radical mastectomy. Sentinel lymph node (SLN) was done in all 26 patients in group A while only 25 patients in group B with 1 patient undergoing axillary dissection from the start. SLN was positive in 8 patients (30.8%) in group A & 6 (24 %) patients in group B. Consequently, 8 patients (30.8%) in group A and 7 patients (26.9%) in group B underwent axillary dissection. Conclusion: Conservative breast cancer surgery after neo-adjuvant therapy in early breast cancer patients in COVID-19 era has comparable results to primary conservative breast surgery. Thus, the obligatory decision to delay primary surgery during COVID-19 era by giving neoadjuvant chemotherapy was effective. Copyright © Celsius Publishing House.

Impact of Covid 19 Pandemic on Elective Rectal Cancer Surgery - Single Institution Experience

Introduction: Surgical treatment of rectal cancer depends on clinical stage, size and location of primary tumor. A sphincter preserving technique such as low anterior resection (LAR) is the preferred method if negative distal margin can be achieved. If an adequate distal margin cannot be obtained, an abdominoperineal resection (APR) is required. A proctosigmoidectomy (Hartmann's procedure) is performed in patients with potentially curable obstructing rectal cancer after neoadjuvant chemoradiotherapy, or as a palliative treatment for locally advanced rectal cancer. Aim(s): The aim of this retrospective study was to investigate the impact of COVID 19 pandemic on the number and type of surgeries performed for the treatment of rectal cancer in UHC Zagreb, Department of Surgery. Material(s) and Method(s): Collected data were extracted from medical records of the patients who underwent surgery at the Department of Surgery from 1st of January 2016 to 31st of December 2022 with prior Ethics Committee approval. Total of 688 patients were included. Retrospective analysis of number and type of surgery was done consecutively by years for the period of interest. Result(s): In 2016 total of 75 patients underwent elective surgery for rectal cancer. LAR was performed in 64% (N=48) of patients, Hartmann's procedure in 20% (N=15), and APR in 16% (N=12). In 2017, 94 surgeries were performed. LAR accounted for 64% (N=60), Hartmann's procedure 17% (N=16), and APR 19% (N=18). In 2018, 115 surgeries were performed. LAR accounted for 69% (N=79), Hartmann's procedure 10% (N=12), and APR 21% (N=24). In 2019, 80 surgeries were performed. LAR accounted for 67% (N=54), Hartmann's procedure 9% (N=80), and APR 24%. In 2020, 78 surgeries were performed. LAR accounted for 59% (N=46), Hartmann's procedure 14% (N=11), and APR 27% (N=21). In 2021, 124 surgeries were performed. LAR accounted for 66% (N=82), Hartmann's procedure 14% (N=17), and APR 20% (N=25). In 2022, 122 surgeries were performed. LAR accounted for 64% (N=78), Hartmann's procedure 15% (N=18), and APR 21% (N=26). Conclusion(s): Our results show steady growth in numbers of performed surgeries in the years prior to the pandemic, with exception of the year 2019 when our department underwent organizational changes. In 2020, significant decrease in number of surgeries was observed as a result of restrictive epidemiological measures established to reduce the spread of COVID 19 infection. COVID 19 pandemic measures also resulted in delayed diagnosis and treatment of rectal cancer which is indirectly shown through the increasing share of Hartmann's procedure. In the years following the relaxation of measures, significant increase in number of performed surgeries that exceeded all the pre-pandemic years was recorded. Constant elevated share of Hartmann's procedure was noted as possible consequence of post COVID delay in diagnosis and confirmation of rectal cancer in more advanced stages of disease.

Not Waiting to Progress; How the COVID-19 Pandemic Nudged Neoadjuvant Therapy for Stage III Locally Advanced Melanoma Patients.

Background: Early-phase neoadjuvant trials have demonstrated promising results in the utility of upfront immunotherapy in locally advanced stage III melanoma and unresected nodal disease. Secondary to these results and the COVID-19 pandemic, this patient population, traditionally managed through surgical resection and adjuvant immunotherapy, received a novel treatment strategy of neoadjuvant therapy (NAT). Methods: Patients with node-positive disease, who faced surgical delays secondary to COVID-19, were treated with NAT, followed by surgery. Demographic, tumour, treatment and response data were collected through a retrospective chart review. Biopsy specimens were analysed prior to the initiation of NAT, and therapy response was analysed following surgical resection. NAT tolerability was recorded. Results: Six patients were included in this case series; four were treated with nivolumab alone, one with ipilimumab and nivolumab and one with dabrafenib and trametinib. Twenty-two incidents of adverse events were reported, with the majority (90.9%) being classified as grade one or two. All patients underwent surgical resection: three out of six patients following two NAT cycles, two following three cycles and one following six cycles. Surgically resected samples were histopathologically evaluated for the presence of disease. Five out of six patients (83%) had ≤1 positive lymph node. One patient showed extracapsular extension. Four patients demonstrated complete pathological response; two had persisting viable tumour cells. Conclusions: In this case series, we outlined how in response to surgical delays secondary to the COVID-19 pandemic, NAT was successfully applied to achieve promising treatment response in patients with locally advanced stage III melanoma.

Magseed wide local excisions - The first 50

Introduction: Prior to 2021, impalpable tumours in our unit were localised with Somatex wires. During the COVID pandemic we introduced Magseed due to its logistical advantages in allowing surgery on a site distant from our breast unit. We wanted to ensure our clinical outcomes with this new system were equivalent to those using wire localisation. Method(s): Electronic records for the first 50 consecutive Magseed localised wide local excisions and the preceding 50 consecutive wire localised wide local excisions were compared. Excision biopsies, palpable lesions, bracketed lesions and post neoadjuvant treatment patients were excluded. Patient demographics, tumour size, inadequate radial margin involvement rate, reoperation rate for margins, specimen weight, number of cavity shaves and operative time were recorded. [Formula presented] Results: Results are shown in table 1. There were no preoperative differences in the two groups. There were no significant differences in outcomes between the two groups, with a trend towards lower margin involvement rates but more shaves in the Magseed group. The mean operative time was slightly shorter in the Magseed group despite more axillary procedures being performed in this group. Conclusion(s): The change to the Magseed system led to logistical advantages with patient outcomes at least equivalent to wire guided excision.Copyright © 2023

Imperial Prostate-4 Comparative Healthcare Research Outcomes of Novel Surgery in Prostate Cancer (Ip4-Chronos): Early Feasibility, Safety and Functional Outcomes from a Pilot Rct

INTRODUCTION AND OBJECTIVE: Randomised comparative outcomes are unavailable for focal therapy in localised prostate cancer. IP4 CHRONOS is an RCT aimed to optimise recruitment of patients dependent upon clinician and patient equipoise. METHOD(S): Patients with clinically significant localised prostate cancer could opt for IP4-CHRONOS-A or IP4-CHRONOS-B. IP4- CHRONOS-A randomised patients 1:1 between focal therapy(HIFU or cryotherapy) versus radical therapy(radiation or prostatectomy). Using a multi-arm-multistage(MAMS)design, IP4-CHRONOS-B randomised between focal alone(FTA) and focal combined with neoadjuvant medication (12 weeks of finasteride [FTF] or bicalutamide [FTB]). We report the pilot phase outcomes on feasibility of randomisation, early safety outcomes relative to treatment and genito-urinary functional outcomes following over 12 months treatment in IP4-CHRONOS-B. IP4-CHRONOS had ethics committee approval and was registered(ISRCTN17796995). RESULT(S): Following COVID-19 adjustments, IP4-CHRONOSA did not meet its feasibility target. Having randomised 36 patients via10 sites with a recruitment rate (95% CI) of 18% (13-23) & randomisation rate of 97%(86-100). IP4-CHRONOS-B did meet its target, randomising 64 patients across 7 sites with a recruitment rate of 43% (35-52) &randomisation rate of 100%(94-100). The only patients to withdraw were randomised to the radical arm of IP4-CHRONOS-A(4 [22%]) All patients in IP4-CHRONOS-B were compliant with neoadjuvant treatment.Only 1 patient reported CTCAE V4.0 grade>=3 adverse event(AE) in IP4-CHRONOS-A following radical treatment, another patient in each arm reported a serious adverse event(SAE) following treatment. 1 &3 patients reported an AE &SAE following FTB. 2 and 3 patients reported an AE &SAE following FTA. No patients reported any AE or SAE event following FTF. Figure 1 demonstrates generally well preserved genito-urinary function following focal treatment+/-neoadjuvant treatment. CONCLUSION(S): IP4-CHRONOS evaluated patient and physician equipoise regarding focal therapy. Traditional randomisation was not feasible due to strong patient preferences, while a MAMS RCT investigating the role of neoadjuvant agents combined with focal therapy was.

Extended Neoadjuvant Chemotherapy in Delayed Primary Resection of Ewing Sarcoma During the COVID-19 Era: A Case Report

CASE: A 13-year-old adolescent boy visited our hospital with a growing mass on his left leg. Investigations and examinations were performed to obtain a final diagnosis of Ewing sarcoma in the head of the left fibula with lung metastasis. Neoadjuvant chemotherapy was extended to 11 courses with radiation before wide tumor resection could be performed. The final 3 adjuvant chemotherapy courses were administered to complete the original protocol while surgical resection complications were also treated. The pathological report revealed free margin resection with nonviable tumor cells. CONCLUSION: An extended neoadjuvant chemotherapy regimen with additional radiation therapy for Ewing sarcoma provided extra local control and allowed limb salvage. Copyright © 2023 by The Journal of Bone and Joint Surgery, Incorporated.

Predictors, surrogate and patient-reported outcomes in neoadjuvant immunotherapy for lung cancer: A single-center retrospective study

Background Development of immunotherapy/molecular targeted therapy has significantly increased survival/QoL in advanced stages of NSCLC. Aim(s): to analyze outcome predictors, surrogate outcomes, and PROMs after neoadjuvant immunotherapy for initially unresectable NSCLC. Methods Initially unresectable NSCLC (2014-2021) patients who received immunotherapy +/- platinum-based chemo and/or radiotherapy evaluated after response (reduction of primary tumor and/or mediastinal lymphadenopathy/control of distant metastatic disease underwent surgical resection). PROMs were recorded using EORTC QLQ-29. Results 19 underwent salvage surgery after ICI. 14 had partial response (73.6%), 5 stable disease. Diagnosis was achieved by endobronchial ultrasound (EBUS) in 8 (42.1%), fine-needle aspiration biopsy (FNAB) in 7 (36.8%), metastasis biopsy in 4 (21.0%). 11 (57.9%) were treated with neoadjuvant platinum-based chemo before or with ICI, 1 (5.2%) pemetrexed before ICI, 5 (26.3%) radiotherapy for metastatic control. 3 (15.7%) had ICI adverse effects. Radiotherapy was never used preoperatively for pulmonary/mediastinal disease. 7 (36.8%) received adjuvant therapy (5 [26.3%] pembrolizumab, 1 [5.2%] pemetrexed, 1 [5.2%] pemetrexed + pembrolizumab). 4 (21.0%) had local relapse (no systemic relapse). Median OS was 19 months (range: 2-57.4). At 2 months, 94.7% were alive (6 months: 89.5%;31 months: 79.5%). 2 (10.5%) had local recurrence. 2 (10.5%) died due to recurrence, 1 (5.2%) to COVID. 4 (21.0%) relapsed (median DFS: 5.3 months [range: 2.2-13.0]). PROMs were reviewed retrospectively at 30 days/1 year with significant decrease in coughing, side effects of treatment, surgery-related problems. [Formula presented] Conclusions Radical surgical resections following definitive immunotherapy/immune-chemotherapy in selected initially unresectable NSCLC are feasible and safe (low surgical-related mortality and morbidity). Symptoms and surgery-related outcomes were lower with higher QoL due to a selected group of highly motivated patients. Legal entity responsible for the study The authors. Funding Ministero della Salute. Disclosure All authors have declared no conflicts of interest.Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc.

Impact of the COVID-19 Pandemic on Breast Cancer Patient Care: A Retrospective Study in a Tertiary Care Center in Lebanon

INTRODUCTION: The COVID-19 pandemic poses challenges to the healthcare systems including cancer treatment. We aim to evaluate the impact of lockdown during COVID-19 on breast cancer (BC) care in terms of BC stage at presentation, treatment compliance and delays, and follow-up in a tertiary care center in Lebanon. METHOD(S): This is a retrospective observational study comparing patients with BC who presented to a tertiary care center in Lebanon in the pre-COVID period (Sep 2019-Dec 2019) and during COVID (Sep 2020-Dec 2020). After receiving the IRB approval, we retrieved the charts of BC patients who had their initial presentation, were under treatment or were on follow-up during our period of interest. We extracted data from electronic medical records of patients related to demographic parameters, cause of visit, tumor description, and type of treatment received. Descriptive analysis, as well as multivariate analysis, were done using SPSS. RESULT(S): Out of the 497 patients included, 274 visited the hospital in the pre-COVID period (median age 52.5 years) and 223 patients during COVID (median age 54.7 years). More than half of patients presented for BC screening in the pre-COVID (52%), while 52% came symptomatic during COVID. Almost 54% had advanced BC at presentation in the COVID period compared to 48% pre-COVID but with no statistical significance (p=0.36). During the COVID period, almost 39% of patients had surgery, 79.7% received chemotherapy, and 21.2% received radiotherapy, but with no significant difference between the two periods. Also, no difference was found in the type of surgery done between the two periods. The mean time between the onset of symptoms and biopsy was significantly longer in the COVID period (4.8 +/- 3.5 months) than that in the pre-COVID (3.2 +/- 5.1 months). The mean time between the biopsy and first treatment was not significantly different between the two periods (1.5 +/- 2.2 months versus 2.1+/-3.8 months). For patients who received neoadjuvant chemotherapy, the mean time between the last chemotherapy and surgery was longer in the COVID period (1.9 +/- 1.4 months) than in the pre-COVID period (1.2 +/- 1.1 months). Multivariate analysis showed that age at diagnosis (p=0.014) and time to diagnosis (p=0.01) were significantly associated with the advanced stage of BC. CONCLUSION(S): This study showed that COVID pandemic has resulted in a delay in the initial presentation of patients resulting in more advanced stages at presentation. However, the management of breast cancer was not substantially impacted by the COVID-19 lockdown.

Unplanned Delay in Time to Operation is Associated With Reduced Recurrence-Free Survival in Colon but Not Rectal Cancer Patients

INTRODUCTION: Patient often experience delays in operative care due to access issues, comorbidities, and other personal reasons. However, during the recent COVID pandemic, hospital resources were severely limited and all patients were forced to endure unprecedented delays, including colon and rectal cancer patients. The oncologic implications of these delays are unknown. METHOD(S): Adult patients who underwent surgery for colon and rectal cancer between January and September of 2020 were retrospectively reviewed. Patients with stage 4 disease were excluded. Patients were categorized as regular or extended interval if time to operation was less than or greater than 40 days for colon cancer and 80 days for rectal cancer. RESULT(S): A total of 186 patients were included, 123 colon cancer and 63 rectal cancer. In the colon cancer group, there were 65 regular interval and 58 prolonged interval patients. There were no significant differences in post-operative, 30-day, or 90-day post-operative outcomes between the two interval groups. During the follow up period (regular vs prolonged: 468.7 +/- 238.3 vs 414.2 +/- 235.5, p = 0.005) there was a higher rate of recurrence in the prolonged group (4.6% vs 17.2%, p = 0.023). Cox regression controlling for disease stage, procedure performed, and resection score demonstrated a significant difference in recurrence-free survival (HR = 7.544, p = 0.007). In the rectal cancer group, there were 48 regular interval and 15 prolonged interval patients. There were no significant differences in postoperative, 30-day, or 90-day outcomes between the two interval groups. During the follow up period (regular vs prolonged: 574.0 +/- 237.3 vs 569.3 +/- 252.2, p = 0.687) there was no difference in recurrence (16.7% vs 26.7%, p = 0.389), but recurrence-free survival was significantly longer in the regular interval group (543.9 +/- 241.6 vs 493.1 +/- 237.4, p = 0.009). However, Cox regression controlling for disease stage, neoadjuvant chemotherapy, procedure performed, resection score demonstrated no difference in recurrence-free survival (HR = 1.403, p = 0.662). CONCLUSION(S): A prolonged time to surgery, greater than 40 days, was associated with decreased recurrence-free survival for color cancer patients. In rectal cancer, no significant reduction in recurrence-free survival was observed despite a longer time to surgery interval in the prolonged group. In events when resources are limited, colon cancer patients may benefit from prioritized treatment and rectal cancer patients may be able to tolerate longer delays without significant impacts on recurrence-free survival.

Benefit from BCON? The unmet need of bladder cancer patients unsuitable for chemoradiation treated with radical radiotherapy alone: A single institution retrospective case note review

Introduction & Objectives: Bladder preservation is routinely used as an alternative to radical cystectomy in the UK and is becoming more accepted elsewhere globally. The gold standard is for patients to receive radiotherapy with a radiosensitiser most commonly concurrent chemotherapy e.g. 5FU/mitomycin C, gemcitabine or cisplatin. Patients with poor performance status or comorbidities may be unable to be offered concurrent treatment with chemotherapy but alternative treatment with concurrent carbogen +/- nicotinamide as a hypoxic modifier may be of benefit. Our aim therefore was to retrospectively review patients with bladder TCC treated with radical radiotherapy alone in the last 5 years who may have benefited from carbogen +/- nicotinamide radiosensitisation at a large cancer centre in the north of England. Material(s) and Method(s): In this single institution retrospective case note review, electronic records were reviewed for 175 patients who had received radiotherapy to the bladder for TCC between 2017-2022. Patients who had radical radiotherapy (RT) alone without radiosensitisation were scrutinised to ascertain whether they would have been candidates for carbogen and nicotinamide using the inclusion/exclusion criteria previously defined in the Bladder Carbogen Nicotinamide (BCON) Randomised Phase 3 trial. Result(s): We analysed 175 patients. Of these, 133 received had radical RT without radiosensitisation. The most common reason for not offering radiosensitisation was the presence of co-morbidities (27.8%). Of interest, the proportion of patients having chemotherapy radiosensitisation did not change after COVID19 in March 2020 (21.5% pre- vs 27.5% post;p=0.32 chi2). Conversely, the proportion of patients receiving neo-adjuvant chemotherapy reduced though failed to reach significance (12.6% pre- vs 5% post;p=0.08 chi2). After review of the notes and criteria from the original BCON trial, 106 patients (79.6%) could have benefited from carbogen +/- nicotinamide. Of these, 14 patients (13.2%) could have been offered carbogen alone due to poor renal function. The most common reason for not being eligible for BCON was respiratory disease with reduced respiratory drive (44%). Conclusion(s): The National Institute for Health and Care Excellence (NICE) state that all radical RT for bladder TCC should be with a radiosensitiser. Due to logistical and departmental issues, the BCON regimen is not currently offered as a standard alternative to radiosensitisation with chemotherapy. BCON has been demonstrated to be tolerable and, whilst updated follow-up data failed to demonstrate statistical significance for overall survival (OS), meta-analysis of hypoxia modification has shown significant improvement in OS compared to RT alone. Hypoxia modification with carbogen +/- nicotinamide should be considered for all patients unsuitable for chemotherapy radiosensitisation.Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Neoadjuvant nivolumab (N) + platinum-doublet chemotherapy (C) for resectable NSCLC: 3-y update from CheckMate 816

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.

PD11-04 Primary results of SOLTI-1503 PROMETEO phase 2 trial of Combination of Talimogene Laherparepvec (T-VEC) with Atezolizumab in patients with residual breast cancer after standard neoadjuvant multi-agent chemotherapy

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.

A retrospective review of primary prophylaxis with granulocyte-colony stimulating factor (G-CSF) for patients with genitourinary malignancies receiving chemotherapy during the COVID-19 pandemic and implications for the future

Background: To mitigate the risks of chemotherapy associated neutropenia, during the COVID-19 pandemic, all genitourinary (GU) cancer patients treated with chemotherapy at the Princess Margaret Cancer Centre (PMCC) were offered primary prophylaxis with GCSF. We hypothesize that this reduced rates of febrile neutropenia, hospitalizations, healthcare costs and improved overall outcomes, compared to GU cancer patients treated with chemotherapy without GCSF in the 2 years prior to the pandemic. Method(s): We performed a retrospective review of GU cancer patients, receiving curative or palliative intent chemotherapy, with or without primary GCSF prophylaxis between January 2018 and June 2022. GCSF was given either as a single dose or as consecutive doses post chemotherapy. Main outcomes were incidence of febrile neutropenia, hospitalization, health care expenditures as well as disease specific outcomes. Result(s): Overall, 248 patients with prostate cancer (44%), urothelial cancers (33%) germ cell (21%), and rare GU cancers (4%) were identified. Median age was 70 (range 19-91), 92% were male, 65% were ECOG 0/1. Treatment intent was neoadjuvant (13%), adjuvant (20%), or palliative (67%). Main regimens used were docetaxel, cabazitaxel, carboplatin, cisplatin/ etoposide, gemcitabine/cisplatin and BEP. Median follow-up was 10.5 months (0.23-52.3 months). A total of 206/248 received primary GCSF prophylaxis. During chemotherapy, the median white blood cell levels were higher in the GCSF group compared to the non-GCSF group (14.1+/-10+/-9/L vs 2.90+/-10+/-9/L, p<0.0001);and neutropenia rates were markedly lower (2% vs. 93%, P=,0.0001). Hospital admission rates were significantly lower in G-CSF users compared to nonusers (19% vs. 69%, P,0.0001). Symptomatic disease progression 13% was the leading cause of admission in the G-CSF group. Infectious causes such as UTI, pneumonia, COVID-19, and sepsis were seen in only 12% of the G-CSF group compared to 31% in the non-users. G-CSF was generally well tolerated with just 0.97% discontinuing G-CSF. Conclusion(s): During the COVID-19 pandemic, primary prophylactic G-CSF use in GU cancer patients, undergoing chemotherapy significantly lowered rates of both febrile neutropenia and hospitalizations and could be a cost-effective strategy in this patient population that warrants further study.

Change in breast cancer detection method, stage at diagnosis and treatment during the COVID19 Pandemic: 2019-2021

Objective: Identify changes in breast cancer detection method, stage at diagnosis and treatment prior to, during and after stay-at-home orders and restricted health care access due to COVID-19. Method(s): Statistical comparison of detection method (patient (PtD), mammography (MamD) or other), Anatomic TNM Stage 8 (0-IV) and invasive BC treatment change over time by three time periods (time 1: 2019+Q1 2020;time 2: Q2-Q4 2020;time 3: 2021) using chi-square analysis in an institutional retrospective cohort of first primary breast cancer (BC) patients (n=1799), years 20192021. Result(s): In the years prior to the study, 2016-2019, there was no difference in detection method or stage at diagnosis by year with 682 to 733 newly diagnosed BC annually (p=.462). In 2020 (n=535) and 2021 (n=582) annual diagnosed cases dropped 22% and 15% from 2019 levels. Compared to time 1, time 2 MamD BC dropped significantly (64% to 58%) with a subsequent increase in MamD BC to 70% in time 3 (p < .001) creating a U-shaped curve for MamD over time. PtD BC increased in time 2 from 30% to 36% but declined in time 3 to 25% (p <.001). Concurrently, stage at diagnosis shifted from time 1 to time 2 with stage 0 and I declining [stage 0: 21% to 16%, stage I: 40% to 38%] and stage II and IV increasing [stage II: 28% to 33%, stage IV: 2% to 4% stage IV] (p<.001). Subsequently in 2021 stage shifted again with an increase in stage 0 to 22% and stage I to 45% and a decline in stage II (33% to 24%), III (9% to 7%) and IV (4% to 2%) (p<.001). Combining stage 0 and I, the percentage of lower stage BC declined from 61% to 54% and increased to 67% in time 3 (2021) when health services became more readily accessible. There was no change in type of surgery for invasive breast cancer (stage I-III, n=1386) with equivalent numbers of breast conserving surgery (58%), subcutaneous mastectomy (24%) and mastectomy (18%) over the time period. Chemotherapy treatment rates for invasive BC did not change (38%). Radiation therapy increased from 66% (time 1: 2019+Q1 2020) to 73% (time 2: Q2Q4 2020) then back to 64% in time 3: 2021 (p=.007) independent of surgery type but concordant with an increase in stage IA and stage IIB BC among invasive breast cancer cases in time 2: Q2-Q4 2020 (p<.001). Likewise, neoadjuvant therapy increased and then declined from 33% to 38% to 29% from time 1 to time 3 (p<.001). Conclusion(s): Number of diagnosed BC cases fell after the first quarter of 2020 during the time of COVID-19 related shut downs and decreased access to health services. During the Q2-Q4 2020 time period mammography detected BC declined with a relative increase in patient detected breast cancer. When mammography detection declined, BC stage at diagnosis shifted to higher stage concurrent with increased rates of radiation and neoadjuvant therapy. In 2021, the relative increase in mammography detected BC indicates a return to more normal screening patterns with a catch up for screening lost in the prior year due to access limitations. In the third time period: 2021, with the return to prior levels of mammography detected breast cancer, stage shifted back to pre-pandemic expected distribution and the excess treatment with radiation and neoadjuvant therapy declined to previously observed levels. Although the changes in detection method, stage and treatment did not persist they were statistically significant and could represent a need for re-establishing prepandemic screening behavior. (Table Presented).

The impact of the COVID19 pandemic on treatment practices for patients diagnosed with early breast cancer: a cross-sectional study from a large comprehensive cancer centre in Italy

The impact of the COVID19 pandemic on treatment practices for patients diagnosed with early breast cancer: a cross-sectional study from a large comprehensive cancer centre in Italy. Introduction: The Coronavirus Disease 2019 (COVID19) has disrupted health services worldwide. The evidence on the impact of the pandemic on cancer care provision, however, is conflicting. Some reports found that management for patients diagnosed with early breast cancer (EBC) during the pandemic did not differ from pre-pandemic practices;other reports suggested that delays in breast cancer surgery may have occurred. We aimed to audit the management of patients diagnosed with EBC during the pandemic in a large, tertiary-level cancer centre in Italy. Method(s): We conducted a cross-sectional study to track the route to first treatment for patients diagnosed with EBC during 2019, 2020, and 2021. We ed data for all consecutive patients referred to the Veneto Institute of Oncology (Padua, Italy). We defined as point of contact (POC) the date of the first consultation with a breast cancer specialist of the breast unit. We considered patients with a first POC in the 6 months preceding the multidisciplinary (MDT) meeting and initiating a treatment within 6 months from the POC. We chose the 3-month period April-June because in 2020 it was when health services were first acutely disrupted. We analysed the same period for 2019 and 2021. First treatment was defined as either upfront surgery or neoadjuvant chemotherapy (NACT). The time to first treatment was defined as the interval between the first POC and the first treatment. We used the median time to first treatment in 2019 to define the threshold for treatment delay. Result(s): We reviewed medical records for 878 patients for whom an MDT report during 2019-2021 (April through June) was available. Of these, 431 (49%) were eligible: 144 in 2019, 127 in 2020 and 150 in 2021. Median age at first POC was 61 years. The proportion of screen-detected tumours was larger in 2019 and 2021 than in 2020 (59%). Conversely, the proportion of screen-detected tumours was offset by the proportion of palpable tumours in 2020 (44% versus 56%). These differences were statistically significant (chi-square test 11.12, p=0.004). Distribution of tumour and nodal stage was unchanged over time, but in-situ tumours were slightly fewer in 2020 than in 2019 or 2021. The odds ratio for treatment delay (45 days or more) was 0.87 for 2020 versus 2019 (95% CI, 0.5-1.53) and 0.9 for 2021 versus 2019 (95% CI, 0.52-1.55), after adjusting for type of POC, presentation with symptoms, treatment type, tumour stage, nodal stage, and EBC subtype (i.e., luminal, HER2positive, triple-negative). Conclusion(s): There was no evidence for major changes in the management of EBC patients during 2019-2021 and no treatment delays were observed. However, our results show a slight decrease in the absolute number of patients being treated in 2020, offset by an increase in 2021 to levels comparable to 2019. Our findings suggest that disruption of breast cancer screening programmes may have impacted on the characteristics of the patient population, with a larger proportion of women presenting with palpable nodules. Validation on a larger, population-based cohort of patients is warranted to robustly assess the impact of the COVID19 pandemic on treatment practices and outcome for EBC patients.