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PURPOSE: Patients with cancer are presumed to be more vulnerable to COVID-19. We evaluated a screening strategy combining chest computed tomography (CT) and reverse-transcription polymerase chain reaction (RT-PCR) for patients treated with radiation therapy at our cancer center located in a COVID-19 French hotspot during the first wave of the pandemic. METHODS AND MATERIALS: Chest CT images were proposed during radiation therapy CT simulation. Images were reviewed by an expert radiologist according to the COVID-19 Reporting and Data System classification. Nasal swabs with RT-PCR assay were initially proposed in cases of suspicious imaging or clinical context and were eventually integrated into the systematic screening. A dedicated radiation therapy workflow was proposed for COVID-19 patients to limit the risk of contamination. RESULTS: From March 18, 2020 to May 1, 2020, 480 patients were screened by chest CT, and 313 patients had both chest CT and RT-PCR (65%). The cumulative incidence of COVID-19 was 5.4% (95% confidence interval [CI], 3.6-7.8; 26 of 480 patients). Diagnosis of COVID-19 was made before radiation therapy for 22 patients (84.6%) and during RT for 4 patients (15.3%). Chest CT directly aided the diagnosis of 7 cases in which the initial RT-PCR was negative or not feasible, out of a total of 480 patients (1.5%) and 517 chest CT acquisitions. Four patients with COVID-19 at the time of the chest CT screening had a false negative CT. Sensitivity and specificity of chest CT screening in patients with both RT-PCR and chest CT testing were estimated at 0.82 (95% CI, 0.60-0.95) and 0.98 (95% CI, 0.96-0.99), respectively. Adaptation of the radiation therapy treatment was made for all patients, with 7 postponed treatments (median: 5 days; interquartile range, 1.5-14.8). CONCLUSIONS: The benefit of systematic use of chest CT screening during CT simulation for patients undergoing radiation therapy during the COVID-19 pandemic seemed limited.

Purpose: Desmoid-type fibromatosis (DF) are locally aggressive neoplasms, with a need for effective systemic treatment in case of progression to avoid the short- and long-term complications of local treatments. Experimental Design: We retrospectively analyzed the outcomes of adult patients with DF treated with oral vinorelbine (90 mg once weekly) at Gustave Roussy Cancer Institute (Villejuif, Paris, France). Only patients with documented progressive disease according to RECIST v1.1 for more than 3 months (±2 weeks) before treatment initiation were included. Results: From 2009 to 2019, 90 out of 438 patients with DF were eligible for this analysis. Vinorelbine was given alone in 56 patients (62%), or concomitantly with endocrine therapy in 34 patients, for a median duration of 6.7 months. A partial response was observed in 29% and stable disease in another 57%. With a median follow-up of 52.4 months, the median time to treatment failure (TTF) was not reached. Progression-free rates at 6 and 12 months were 88.7% and 77.5%, respectively. Concomitant endocrine therapy was associated with longer TTF in women [HR, 2.16; 95% confidence interval (CI), 1.06–4.37; P = 0.03). Among 64 patients with documented CTNNB1 mutational status, p.S45F or p.S45P mutations were associated with longer TTF compared with p.T41A or wild-type tumors (HR, 2.78; 95% CI, 1.23–6.27; P = 0.04). Toxicity profile was favorable, without grade 3–4 toxicity, except for one grade 3 neutropenia. Conclusions: Oral vinorelbine is an effective, affordable, and well-tolerated regimen in patients with advanced, progressive DF. Prolonged activity was observed in patients with tumors harboring CTNNB1 p.S45F or p.S45P mutations.

Patients with cancer are presumed to be at increased risk of severe COVID-19 outcomes due to underlying malignancy and treatment-induced immunosuppression. Of the first 178 patients managed for COVID-19 at the Gustave Roussy Cancer Centre, 125 (70.2%) were hospitalized, 47 (26.4%) developed clinical worsening and 31 (17.4%) died. An age of over 70 years, smoking status, metastatic disease, cytotoxic chemotherapy and an Eastern Cooperative Oncology Group score of ≥2 at the last visit were the strongest determinants of increased risk of death. In multivariable analysis, the Eastern Cooperative Oncology Group score remained the only predictor of death. In contrast, immunotherapy, hormone therapy and targeted therapy did not increase clinical worsening or death risk. Biomarker studies found that C-reactive protein and lactate dehydrogenase levels were significantly associated with an increased risk of clinical worsening, while C-reactive protein and D-dimer levels were associated with an increased risk of death. COVID-19 management impacted the oncological treatment strategy, inducing a median 20 d delay in 41% of patients and adaptation of the therapeutic strategy in 30% of patients. Barlesi and colleagues describe the determinants of severe COVID-19 outcomes in patients with cancer managed at the Gustave Roussy Cancer Centre.

Background Nivolumab and pembrolizumab were initially developed using weight-based regimen doses. Recently, fixed-dose regimens were commercialised with reference weights higher than the accurate weight of patients with cancer in routine practice. This may have important economic consequences for healthcare systems. Material and methods Budget impact analysis was performed using real-world data both from Gustave Roussy database and the French National Hospital Discharge database and including patients treated with either nivolumab or pembrolizumab at Gustave Roussy and in France before the approval of fixed-dosing regimens in Europe. Main outcome is the expected annual budget impact of fixed-dosing regimens in France. Results From January to April 2018, 978 perfusions of anti–programmed cell death protein 1 were administered at our institution including 560 perfusions of nivolumab in 103 patients and 418 perfusions of pembrolizumab in 125 patients mainly treated for lung cancer and melanoma. The mean extra cost attributable to flat doses would have amounted to €284 (95% confidence interval [CI]: 241–327) per infusion of nivolumab and to €1287 (95% CI: 1200–1373) per infusion of pembrolizumab. Annually, at Gustave Roussy, it would represent an extra cost of € 477 120 (95% CI: 404 880–549 360) and €1 613 898 (95% CI: 1 504 800–1 721 742), respectively, for the year 2018. At the French national level, the expected annual budget impact is estimated at €55 162 211 for the year 2017. Conclusions Weight references for fixed-dose regimens do not reflect the accurate mean weight of patients under cancer treatment and are likely to have substantial economic impact for healthcare systems.

Background Our objective was to describe the clinical course, risk factors and outcomes of patients infected with COVID-19 around the globe comparing cancer to non-cancer patients. Methods We conducted a retrospective cohort study of COVID-19 confirmed cases through an international multicenter collaboration including 17 centers around the world including the United States of America, Brazil, Europe, Far East, Middle East and Australia from January to date. We evaluated the patients’ clinical characteristics, clinical course of the disease, hospitalization and outcome. Death was considered to be COVID-associated if it occurred within 30 days from the time of diagnosis. Results Preliminary data on 571 patients included 186 cancer patients and 385 non-cancer patients. Cancer patients were more likely to have COPD and received steroids but were less likely to have COVID-related symptoms compared to non-cancer patients (84% vs 97%, p< 0.0001). The rate of pneumonia with hypoxia, non-invasive ventilation and mechanical ventilation were similar in both groups. Despite the fact that hospital admissions were significantly higher in non-cancer patients (70% vs 56%, p< 0.001), promising antiviral and immune-related therapy including remdesivir, convalescent plasma and immunomodulators were more commonly used in cancer patients compared to non-cancer patients (P=0.04). Cancer patients had a higher COVID-associated mortality rate compared to non-cancer patients (20% vs 11%, p=0.006). Conclusion Despite the fact that cancer patients received more frequent antiviral and immune-related therapy, the mortality rate among cancer patients was significantly higher than non-cancer patients. Disclosures Roy F. Chemaly, MD, MPH, FACP, FIDSA, Chimerix (Consultant, Research Grant or Support)Clinigen (Consultant)Merck (Consultant, Research Grant or Support)Novartis (Research Grant or Support)Oxford Immunotec (Consultant, Research Grant or Support)Shire/Takeda (Research Grant or Support)Viracor (Research Grant or Support) Issam I. Raad, MD, Citius (Other Financial or Material Support, Ownership interest)Cook Medical (Grant/Research Support)Inventive Protocol (Other Financial or Material Support, Ownership interest)Novel Anti-Infective Technologies (Shareholder, Other Financial or Material Support, Ownership interest)

Therapeutic options in patients with metastatic osteosarcoma are limited and effective systemic treatments are needed in this setting. The aim of this case series was to assess the efficacy and toxicity of oral metronomic etoposide in adult patients with progressive metastatic osteosarcoma. We retrospectively reviewed the electronic records of patients treated with oral metronomic etoposide (25 mg thrice daily, 3 weeks out of 4) from December 2002 to December 2018 at Gustave Roussy (Villejuif, France). The primary endpoint was progression‐free rate (PFR) at 4 months; secondary endpoints were: best response (according to RECIST v1.1), progression‐free survival (PFS), overall survival (OS) and safety. With a median follow‐up of 9.8 months, 37 patients were eligible for this analysis: 68% males, median age 42 (range: 21–75), 19% with synchronous metastases, 92% with lung metastases, median PS: 1 (range: 0–3). Median number of previous treatment lines in the metastatic setting was 1 (range: 0–4). Progression‐free rate at 4 months was 40.3% (95% CI: 24.5–56.2). Best response was partial response in 11% and stable disease in 35% of patients (disease control rate: 46%). Median PFS was 3.1 months (95% CI: 2.5–4.7) and median OS was 9.8 months (95% CI: 5.1–12.3). Toxicity profile was acceptable, with 13% grade 3 haematological toxicities (anaemia and neutropenia), without any grade 3–4 non‐haematological toxicity. In our experience, oral metronomic etoposide demonstrated effective palliation along with acceptable toxicity in patients with progressive metastatic osteosarcoma., Oral metronomic etoposide demonstrated effective palliation (progression‐free rate at 4 months was 40.3% (95%CI: 24.5‐56.2), along with acceptable toxicity in adult patients with metastatic osteosarcoma.

Background: The SARS-CoV-2 outbreak significantly affected Gustave Roussy cancer center Here, we report the Gustave Roussy experience on older patients (OP) with cancer during the SARS-CoV-2 outbreak Methods: Cancer pts with suspected SARS-CoV-2 infection were admitted at Gustave Roussy starting March, 12th Screening indications have been adapted over time All the COVID-19 pts positively tested and managed at Gustave Roussy between March 14th and April 15th have been included in a redcap database Pts and underlying oncological and COVID-19 diseases characteristics have been collected Cancer and COVID-19 managements, and outcomes have been assessed The primary endpoint of this analysis was the clinical deterioration, defined as the need for O2 supplementation of 6l/min or more, or death of any cause Results: Among the first 137 cancer pts diagnosed with SARS-CoV-2, 36 patients were aged 70 years old or over (26%) Most of them were female (61%) with a median age of 75 5 years old Most frequent underlying cancers were solid tumors (92%) including GI (19%), lung (17%), GYN (14%) and head and neck (14%) Most OP (36%) were ECOG Performans status 2 versus 24% in younger patients (YP) The diagnosis of SARS-CoV-2 infection was made by RT-PCR or thoracic CT scan alone in 97% and 3% of the cases, respectively in OP and in 92% and 8% in YP Most OP experienced symptoms prior to testing (92%) compared to YP (80%) Symptoms differed according to age with more cough with sputum production in OP (14% versus 5%), dyspnea (39% versus 31%), diarrhea (17% versus 9%), shivers (8% versus 0%), sore throat (8% versus 4%) and no anosmia nor agueusia The majority of OP was hospitalized (81%) compared to 72% of YP and treated with HCQ/AZI (15;52%) compared to 25 (35%) YP with inclusion in the ONCOVID trial (EudraCT: 2020-01250-21) They did not receive any IL-6 inhibitor Only one OP was admitted in the ICU (3%) Clinical deterioration occurred in 10 OP (29%) There was no impact of age on clinical worsening (HR=1 157;95%CI 0 55-2 42;p=0 7) However age was associated with worse overall survival (OS) (HR=2 45 95%CI 1 02-5 92;p=0 0463) Results will be updated at the meeting Conclusions: OP with cancer had a different disease presentation, same rate of clinical worsening but worse OS in SARS-CoV-2 infection Legal entity responsible for the study: The authors Funding: Has not received any funding Disclosure: All authors have declared no conflicts of interest

In digestive oncology, the clinical impact of targeted next-generation sequencing (NGS) in routine practice should be addressed. In this work, we studied the impact of a 22-gene NGS amplicon-based panel with Ion Torrent Proton Sequencing, prospectively performed in routine practice. We analyzed the results of extended molecular testing, beyond RAS and BRAF, in metastatic colorectal cancer (mCRC) patients in a single-center, retrospective, observational study of consecutive mCRC patients followed up at the Georges Pompidou European Hospital between January 2016 and December 2018. Overall, 210 patients with mCRC were included. Median follow-up was 25.4 months (IQR: 14.9–39.5). The three most frequently mutated genes were: TP53 (63%), KRAS (41%) and PIK3CA (19%). A positive association was found between overall survival and performance status (PS) ≥ 2 (HR: 4.91 (1.84–13.1), p = 0.001) and differentiation (HR: 4.70 (1.51–14.6), p = 0.007) in multivariate analysis. The NGS panel enabled five patients to access a targeted therapy not currently registered for CRC. In conclusion, targeted NGS panels in mCRC are feasible in routine practice, but need to be regularly updated and in-depth studies are needed to better analyze the prognostic factors.

Background: The COVID-19 pandemic deeply threatens the rigorous conduct of clinical trials, notably by delaying site initiation visits, patient enrolment, treatment administration, trial-associated procedures, and data monitoring. Unlike most other medical specialties, clinical trials are an integral part of patient care in oncology. Limiting access to clinical trials therefore results in a loss of chance for patients. Methods: In this retrospective single-center study, we collected clinical trial-specific items (including patient-related or trial management-related items) during the first pandemic wave (March– June 2020) and lockdown (March 17th-May 11th) at Gustave Roussy, and compared them to those of the same period in 2019. Results: In March 2020, 84 phase I (P1) and 210 phase II/III (P2/3) trials were open. During the first pandemic wave, 21 (25%) P1 and 20 (9%) P2/3 trials were temporarily halted, following a unilateral sponsor decision in virtually all cases;all but one were industry-sponsored. Despite this, all important metrics of the P1/2 trial activity remained similar to those of 2019, including the number of patients referred for inclusion (599 vs 620), inclusion consultations (215 vs 247), patients starting treatment (130 vs 130), Internal Review Board (IRB) submissions (14 vs 16), and site initiation visits (11 vs 15), all in 2020 vs 2019, respectively. The impact of the first lock-down was more marked on P2/3, with 152 patient inclusions (vs 346 in 2019), 125 randomizations (vs 278), 43 IRB submissions (vs 50) and 34 site initiation visits (vs 40). However, in parallel, 475 patients were included in three “COVID and cancer” trials. Among the 443 P1 and 2851 P2/3 patients, 198 and 628 COVID-19 PCR were performed internally, and five and 15 (2.5%) were positive, respectively. One patient with a community-based COVID-19 died after transfer in intensive care. Conclusions: Cancer clinical trials can, and must be maintained despite challenges brought by COVID-19. Sharing experiences and retrospectively evaluating the impact on patients’ safety and cancer-related outcomes will be critical to durably improve the clinical trials conduct and to anticipate at best challenges brought by future similar crises. Legal entity responsible for the study: Gustave Roussy. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Background: Outcomes and risk factors associated with COVID-19 worsening among cancer patients have previously been reported. However, the actual impact of SARs-Co-V2 infection on the cancer treatment strategy remains unknown. Here, we report the Gustave Roussy (GR) experience, one year after the onset of the pandemic focusing on the impact of COVID-19 in patients with ongoing management of oncohematological disease. Methods: All patients positively tested for SARS-CoV-2 and managed at GR between Mar 14th 2020 and Feb 15th 2021 (data cut-off) have been included. Patients underlying oncohematological disease and COVID19 characteristics have been collected. Cancer and COVID-19 management and outcomes have been assessed. Primary endpoint was the overall impact of COVID-19 on oncological and hematological treatment strategy assessed at 1, 3, 6 and 12 months. Results: At the time of the analysis, 423 patients (median age: 62 years) were found positive for SARS-CoV-2 and managed at GR with a median follow up of 5.6 months (0-13 months). Among them, 284 (67%) were admitted due to COVID-19. Clinical deterioration occurred in 87 patients (21%), 43 patients (10%) were transferred in intensive care unit and 123 (29%) patients died, among which 47 (11%) died from COVID-19. Overall, 329 (78%) patients were on active treatment for underlying oncohematological disease at time of COVID diagnosis. Impact of COVID-19 on cancer treatment strategy in those patients is presented in the Table. The majority (N=268, 81%) had no change in oncological strategy. For those who experienced a delay, median delay in treatment was 21 days (N=99, [1-77]), 30 days (N=15, [15-56]), 7 days (N=8,[3-35]) for systemic treatment, surgery and radiotherapy respectively. [Formula presented] Conclusions: COVID-19 outbreak is associated with a significant mortality in patients with cancer. However, for patients who did not die from COVID-19, we provide the first report supporting that ongoing treatment was maintained or could be resumed in the majority of cases in a timely manner. Legal entity responsible for the study: Gustave Roussy. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

We thank Zheng and colleagues for their interest in our article long-term outcomes of oral vinorelbine in advanced, progressive desmoid fibromatosis and influence of CTNNB1 mutational status ([1][1]). Their letter addresses relevant points concerning the use of a fixed dose of vinorelbine, and the

Background: The SARS-CoV-2 outbreak in Paris’s region significantly affected Gustave Roussy Cancer Center. Previous analyses showed that mortality rate increases with age in the general population. Here, we report the Gustave Roussy experience on older patients (OP) with cancer during the SARS-CoV-2 outbreak. Methods: Cancer pts with suspected SARS-CoV-2 infection were admitted at Gustave Roussy starting March 12th. Screening indications have been adapted over the time. All the COVID19 pts positively tested and managed at Gustave Roussy between March 14th (1st positive case) and April 15th have been included in a REDCap database. Pts and underlying oncologic and COVID19 diseases characteristics have been collected. Cancer and COVID-19 managements and outcomes have been assessed. The primary endpoint of this analysis was the clinical deterioration, defined as the need for O2 supplementation of 6l/min, or death of any cause. Results: Among the first 137 cancer pts diagnosed with SARS-CoV-2, 36 patients were aged 70 years (26%). Most of them were female (61%) with a median age of 75.5 years old. Most frequent underlying cancers were solid tumors (92%) including GI (19%), lung (17%), GYN (14%), and head and neck (14%). Most OP (36%) were ECOG performance status 2 versus 24% in younger patients (YP). The diagnosis of SARS-CoV-2 infection was made by RT-PCR or thoracic CT scan alone in 97% and 3% of the cases, respectively, in OP and in 92% and 8% in YP. Most OP experienced symptoms prior to testing (92%) compared to YP (80%). Symptoms differed according to age with more cough with sputum production in OP (14% versus 5%), dyspnea (39% versus 31%), diarrhea (17% versus 9%), shivers (8% versus 0%), sore throat (8% versus 4%), and no anosmia or agueusia. The majority of OP were hospitalized (81%) compared to 72% of YP and treated with HCQ/AZI (15; 52%) with inclusion in the ONCOVID trial (EudraCT: 2020-01250-21) compared to 25 (35%) YP. They did not receive any IL-6 inhibitor. Only one OP was admitted in the ICU (3%). Clinical deterioration occurred in 10 OP (29%). There was no impact of age on clinical worsening (HR=1.157; 95%CI 0.55-2.42; p=0.7). However, age was associated with worse overall survival (OS) (HR=2.45 95%CI 1.02-5.92 ; p=0.0463). Results will be updated at the meeting. Conclusions: OP with cancer had a different disease presentation, same rate of clinical worsening, but worse OS in SARS-CoV-2 infection. Citation Format: Mathilde Hauchecorne, Capucine Baldini, Stéphanie Foulon, Arnaud Bayle, Bertrand Gachot, Fanny Pommeret, Helene Vincent, Tina Lamy, Celine Nagera, Christophe Willekens, Franck Griscelli, Florence Netzer, Corinne Balleyguier, Samy Ammari, Fabrice André, Florian Scotte, Benjamin Besse, Jean-Charles Soria, Fabrice Barlési, Laurence Albigès. Outcome of older cancer patients infected with Covid19 at Gustave Roussy Cancer Center [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-030.