Association of COVID-19 Lockdown With the Tumor Burden in Patients With Newly Diagnosed Metastatic Colorectal Cancer

Abstract

IMPORTANCEThe COVID-19 pandemic has been associated with substantial reduction in screening, case identification, and hospital referrals among patients with cancer. However, no study has quantitatively examined the implications of this correlation for cancer patient management.OBJECTIVE To evaluate the association of the COVID-19 pandemic lockdown with the tumor burden of patients who were diagnosed with metastatic colorectal cancer (mCRC) before vs after lockdown. DESIGN, SETTING, AND PARTICIPANTSThis cohort study analyzed participants in the screening procedure of the PANIRINOX (Phase II Randomized Study Comparing FOLFIRINOX + Panitumumab vs FOLFOX + Panitumumab in Metastatic Colorectal Cancer Patients Stratified by RAS Status from Circulating DNA Analysis) phase 2 randomized clinical trial. These newly diagnosed patients received care at 1 of 18 different clinical centers in France and were recruited before or after the lockdown was enacted in France in the spring of 2020. Patients underwent a blood-sampling screening procedure to identify their RAS and BRAF tumor status. EXPOSURES mCRC. MAIN OUTCOMES AND MEASURESCirculating tumor DNA (ctDNA) analysis was used to identify RAS and BRAF status. Tumor burden was evaluated by the total plasma ctDNA concentration. The median ctDNA concentration was compared in patients who underwent screening before (November 11, 2019, to March 9, 2020 vs after (May 14 to September 3, 2020) lockdown and in patients who were included from the start of the PANIRINOX study. RESULTS A total of 80 patients were included, of whom 40 underwent screening before and 40 others underwent screening after the first COVID-19 lockdown in France. These patients included 48 men (60.0%) and 32 women (40.0%) and had a median (range) age of 62 (37-77) years. The median ctDNA concentration was statistically higher in patients who were newly diagnosed after lockdown compared with those who were diagnosed before lockdown (119.2 ng/mL vs 17.3 ng/mL; P < .001).Patients with mCRC and high ctDNA concentration had lower median survival compared with those with lower concentration (14.7 [95% CI,.0] months vs 20.0 [95% CI, 14.1-32.0] months). This finding points to the potential adverse consequences of the COVID-19 pandemic and related lockdown.CONCLUSIONS AND RELEVANCE This cohort study found that tumor burden differed between patients who received an mCRC diagnosis before vs after the first COVID-19 lockdown in France. The (continued) Key Points Question What is the implication of the COVID-19 lockdown for the tumor burden of patients with a newly diagnosed metastatic colorectal cancer? Findings In this cohort study of 80 patients with metastatic colorectal cancer, the tumor burden, which was evaluated using the circulating tumor DNA in plasma, appeared to be significantly higher in patients who received a diagnosis after lockdown compared with those who were diagnosed before lockdown (119.2 ng/mL vs 17.3 ng/mL). Patients with greater tumor burden had lower median survival than those with lower tumor burden.M...

Impact of two waves of Sars‐Cov2 outbreak on the number, clinical presentation, care trajectories and survival of patients newly referred for a colorectal cancer: A French multicentric cohort study from a large group of university hospitals

“…Previous evidence shows that the outbreak‐related policies have induced delays in CRC diagnostic procedures, but these policies may have also increased time‐to‐treatment after diagnosis. Patients with a new CRC diagnosed after the beginning of the Sars‐Cov2 outbreak period may be more likely to suffer from more advanced tumors at the initial clinical presentation, and to experience poorer outcomes 12‐16 . Local extension of CRC may induce life‐threatening complications such as bowel obstruction, intestinal perforation and/or digestive hemorrhage requiring high‐risk surgical procedures being performed with no delay.…”

“…Patients with a new CRC diagnosed after the beginning of the Sars‐Cov2 outbreak period may be more likely to suffer from more advanced tumors at the initial clinical presentation, and to experience poorer outcomes. 12 , 13 , 14 , 15 , 16 Local extension of CRC may induce life‐threatening complications such as bowel obstruction, intestinal perforation and/or digestive hemorrhage requiring high‐risk surgical procedures being performed with no delay. Diagnosis delays for new CRC cases may also have increased the rate of unresectable tumors.…”

The Role of Shared Decision-Making in Personalised Medicine: Opening the Debate

“…Indeed, during the COVID-19 pandemic, physicians should be cautious due to the mental and emotional strain imposed by consecutive restrictions for them and their patients, e.g., restrictions in the hospital, such as family visits being forbidden during particularly severe moments in the pandemic. The situation makes them keep on track with the clinical evolution and emphasises the need to monitor patients' well-being to preserve their mental health (e.g., patients' distress), although the uncertainty that characterises the times of the pandemic requires mental health care for physicians [18]. In this case, SDM can facilitate continuous observation from both agents (surgeons and cancer patients) to ensure positive preoperative and postoperative phases, or even face the risk of the patients' fear of COVID-19 infection.…”

“…Similarly significant, in this case, is the fact that the situation was most likely aggravated by the restrictions mandated as part of the first lockdown in Madrid (Spain). Nonetheless, although CRC management in pandemic times now follows special guidance for delivering care (e.g., European Society for Medical Oncology), the first extended and restricted lockdowns decreased surveillance and advance-care planning worldwide [18,21]. To prevent these consequences, one key factor involves precisely improving the communication strategy to deal with diagnosis and treatment backlogs by linking the clinical and personal components [21], in which SDM within PMM offers a solution still in progress due to complexities such as those highlighted in the first three cases.…”

Autophagy: The Potential Link between SARS-CoV-2 and Cancer

“…Although this observation is likely due to a multitude of factors, it is possible that defects in autophagy and increased tumor immune evasion among patients with certain malignancies who had previously contracted this infection could have led to more a rapid progression of their cancer due to the processes described above. In addition, a 6.9-fold increase in tumor burden has been reported in patients who had been diagnosed with metastatic colorectal cancer after the first lockdown compared with those diagnosed prior to the lockdown [40]. Despite the significant role of the delays in the screening and diagnosis as a result of the COVID-19-related lockdown, the above-mentioned processes could have also contributed to this observation.…”