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CME / ABIM MOC / CE

COVID-19: How Did the Pandemic Lockdown Affect Cancer Survival?

  • Authors: News Author: Roxanne Nelson, RN, BSN; CME Author: Laurie Barclay, MD
  • CME / ABIM MOC / CE Released: 10/29/2021
  • THIS ACTIVITY HAS EXPIRED
  • Valid for credit through: 10/29/2022
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Target Audience and Goal Statement

This activity is intended for hematologists/oncologists, family medicine/primary care clinicians, gastroenterologists, infectious disease clinicians, internists, nurses, pharmacists and other members of the healthcare team for patients with cancer during the COVID-19 pandemic.

The goal of this activity is to describe the association of the COVID-19 pandemic lockdown with circulating tumor DNA (ctDNA), used as a measure of tumor burden, of patients who were diagnosed with metastatic colorectal cancer (mCRC) before vs after lockdown, according to results from a cohort study of participants in the screening procedure of the PANIRINOX phase 2 randomized, controlled trial (RCT).

Upon completion of this activity, participants will:

  • Describe the association of the COVID-19 pandemic lockdown with tumor burden of patients who were diagnosed with mCRC before vs after lockdown, according to results from a cohort study of participants in the screening procedure of the PANIRINOX phase II RCT
  • Identify clinical implications of the association of the COVID-19 pandemic lockdown with tumor burden of patients who were diagnosed with mCRC before vs after lockdown, according to results from a cohort study of participants in the screening procedure of the PANIRINOX phase II RCT
  • Outline implications for the healthcare team


Disclosures

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Medscape, LLC encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content.


News Author

  • Roxanne Nelson, RN, BSN

    Freelance writer, Medscape

    Disclosures

    Disclosure: Roxanne Nelson, RN, BSN, has disclosed no relevant financial relationships.

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer
    Medscape, LLC

    Disclosures

    Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.

Editor

  • Stephanie Corder, ND, RN, CHCP

    Associate Director, Accreditation and Compliance
    Medscape, LLC

    Disclosures

    Disclosure: Stephanie Corder, ND, RN, CHCP, has disclosed no relevant financial relationships.

CME Reviewer/Nurse Planner

  • Leigh A. Schmidt, MSN, RN, CMSRN, CNE, CHCP

    Associate Director, Accreditation and Compliance
    Medscape, LLC

    Disclosures

    Disclosure: Leigh A. Schmidt, MSN, RN, CMSRN, CNE, CHCP, has disclosed no relevant financial relationships.

CE Reviewer

  • Esther Nyarko, PharmD

    Director, Accreditation and Compliance
    Medscape, LLC

    Disclosures

    Disclosure: Esther Nyarko, PharmD, has disclosed no relevant financial relationships.

None of the nonfaculty planners for this educational activity have relevant financial relationship(s) to disclose with ineligible companies whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.


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CME / ABIM MOC / CE

COVID-19: How Did the Pandemic Lockdown Affect Cancer Survival?

Authors: News Author: Roxanne Nelson, RN, BSN; CME Author: Laurie Barclay, MDFaculty and Disclosures
THIS ACTIVITY HAS EXPIRED

CME / ABIM MOC / CE Released: 10/29/2021

Valid for credit through: 10/29/2022

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Note: The information on the coronavirus outbreak is continually evolving. The content within this activity serves as a historical reference to the information that was available at the time of this publication. We continue to add to the collection of activities on this subject as new information becomes available. It is the policy of Medscape Education to avoid the mention of brand names or specific manufacturers in accredited educational activities. However, manufacturer names related to COVID-19 vaccines may be provided in this activity to promote clarity. The use of manufacturer names should not be viewed as an endorsement by Medscape of any specific product or manufacturer.

Clinical Context

The COVID-19 pandemic has strained health systems worldwide, substantially affecting cancer care. People have avoided healthcare facilities for fear of infection, particularly patients with cancer, which is linked to worse COVID-19 prognosis.

Study Synopsis and Perspective

Many have predicted that the lockdowns and restrictions to contain the COVID-19 pandemic will lead to delays in diagnosis and treatment of cancer and will eventually result in worse outcomes. Now there are data to show that this may indeed be the case.

The data come from France, where the first mandatory lockdown (March-May 2020) lasted 55 days: People had to stay home, and leaving the house was strictly controlled by police. Many medical services were suspended.

The study analyzed data collected during the enrollment phase for a phase 2 clinical trial. As part of the procedure, participants had a blood test to allow analysis of circulating tumor DNA (ctDNA), which was used as a measure of tumor burden.

The team looked at patients who were screened during 2 periods: before the lockdown (from November 11, 2019 to March 9, 2020) and after lockdown (from May 14 to September 3, 2020, a 112-day period).

They found that individuals diagnosed with metastatic colorectal cancer (mCRC) after the lockdown had a tumor burden nearly 7 times higher than persons diagnosed before the pandemic.

In addition, among patients with the higher tumor burden, median survival decreased from 20 months to just less than 15 months.

"The differences in tumor burden between patients who were diagnosed before vs after lockdown and the resulting risk of reduced survival point to the association between the pandemic-related lockdown and unfavorable consequences for patients with newly diagnosed mCRC, who may have delayed their first visit to an oncologist," the researchers commented.

"To our knowledge, this study was the first to assess the association between COVID-19 restrictions and delayed treatment and diagnostic services for a specific cancer," the researchers noted.

 "I think that reasons for diagnosis delays are similar in the US as in France," commented lead author Alain Thierry, PhD, director of research, Institut de Recherche en Cancérologie de Montpellier, France. "They imply individual reluctance or fears or difficulty of carrying out a screening test or to visit a medical doctor or an oncologist during the lockdown period," he told Medscape Medical News.

The study was published September 1 in JAMA Network Open.[1]

Seen in Clinical Practice

"The results of this study are highly believable, and certainly consistent with what I have seen in my own practice," commented Theodore S. Hong, MD, director of gastrointestinal services at Mass General Cancer Center, Boston, Massachusetts.

Colorectal cancer and gastrointestinal cancers, in general, often present with vague, nonspecific symptoms, he continued.

"Delayed screening very likely leads to advanced cancers, and it is highly likely that the pandemic raised the threshold that patients would seek medical care for subacute symptoms," he said. "This is leading to many patients presenting with advanced gastrointestinal cancers."

Delays and Projected Outcomes

The COVID-19 pandemic put an unprecedented burden on global health systems and had substantial implications for cancer care. Routine care (eg, screening) was delayed, and patients were often reluctant to come to healthcare facilities for fear of infection with COVID-19. For example, a study in April[2] from the American Cancer Society Cancer Action Network[2] found that half of the patients with cancer and survivors who responded to a survey conducted during the lockdown last year reported changes, delays, or disruptions to the care they were receiving.

Perhaps most daunting was a model created by the National Cancer Institute (NCI)[3] that predicted tens of thousands of excess cancer deaths would occur over the next decade as a result of missed screenings, delays in diagnosis, and reductions in oncology care caused by the COVID-19 pandemic.

Norman "Ned" Sharpless, MD, director of the NCI, said at the time: "I am deeply concerned about the potential impacts of delayed diagnoses and deferred or modified treatment plans on cancer incidence and mortality."

He also predicted that the number of excess deaths per year would peak in the next year or two, likely sooner for colorectal than for breast cancer, but "for both cancer types, we believe the pandemic will influence cancer deaths for at least a decade."

Worse Outcomes After Lockdown

The study from France involved patients with mCRC who had participated in the PANIRINOX phase 2 clinical trial, which compared treatment with leucovorin calcium (folinic acid)/5-fluorouracil/irinotecan hydrochloride/oxaliplatin (FOLFIRINOX) plus panitumumab to treatment with leucovorin calcium (folinic acid)/5-fluorouracil/oxaliplatin (FOLFOX) plus panitumumab.

To enroll in this trial, patients were stratified by RAS and BRAF status determined from ctDNA analysis.

For the current study, the authors looked again at the ctDNA but this time looked at ctDNA concentrations and used this as a marker of tumor burden.

The median ctDNA concentration was statistically higher in patients who had received their cancer diagnosis after lockdown as compared with patients diagnosed before lockdown (119.2 ng/mL vs 17.3 ng/mL; P < .001). In addition, patients with mCRC and high ctDNA concentration also had lower median survival vs patients with lower concentration (14.7 [95% CI: 8.8, 18] vs 20 [95% CI: 14.1, 32] months).

Thierry and colleagues now plan to examine the full consequences of the lockdown in regard to patient survival in a future 3-year survival study.

"Our data points first to the crucial importance of early detection," said Thierry. "Second, to maintain screening programs and diagnostic services during a pandemic and third, to the needs of requiring intervention to minimize a patient's fears by ensuring high communication/information."

The PANIRINOX study was funded by Amgen Inc. and sponsored by Unicancer Research and Development. Co-author Brice Pastor, PhD, was supported in part by grant INCa_Inserm_DGOS_12553 from SIRIC Montpellier Cancer. Thierry was supported by INSERM.

Thierry has disclosed being a shareholder of DiaDx SAS; several co-authors reported relationships with industry as noted in the paper. Hong reports consulting for Boston Scientific; Inivata; Merck & Co., Inc.; Novocure; and Synthetic Biologics, Inc.; serving on the scientific advisory board for Lustgarten and PanTher Therapeutics (Equity); and has received research funding for clinical trials from AstraZeneca Pharmaceuticals LP; Bristol-Myers Squibb Company; GlaxoSmithKline; IntraOp; Ipsen; Puma; and Taiho Pharmaceutical Co., Ltd.

Study Highlights

  • The study cohort included 80 participants in the screening procedure of the PANIRINOX phase 2 RCT who were newly diagnosed with mCRC and recruited before (n = 40) or after (n = 40) the France lockdown in spring 2020.
  • Median age was 62 (range, 37-77) years; 60% were men.
  • Patient characteristics were not different in the groups diagnosed before vs after lockdown.
  • Median plasma ctDNA concentration was dramatically higher in patients newly diagnosed after vs before lockdown (119.2 ng/mL vs 17.3 ng/mL; P < .001; 6.9-fold increase).
  • Median survival was lower in patients with mCRC and high vs lower ctDNA concentration (14.7 [95% CI: 8.8, 18] vs 20 [14.1, 32] months; P = .005).
  • In the post-lockdown cohort, ctDNA concentration was significantly associated with increased LDH (r = 0.72; P < .001) and white blood cell count (r = 0.73; P < .001).
  • Carcinoembryonic antigen was associated with increased ctDNA in the pre-lockdown (r = 0.38; P = .04) and post-lockdown (r = 0.22; P = .24) groups.
  • The investigators concluded that increased ctDNA concentration after lockdown reflects tumor burden levels at diagnosis, which are associated with patient survival.
  • The findings highlight potential adverse consequences of the COVID-19 pandemic and lockdown and suggest that CRC is a major area for intervention to minimize pandemic-associated delays in screening, diagnosis, and surgical treatment.
  • Patients with newly diagnosed mCRC may have delayed their first visit to an oncologist.
  • Patients’ reluctance to visit a physician or healthcare facility during the beginning of the COVID-19 pandemic may help explain the lower number of mCRC diagnoses.
  • The pandemic also caused considerable delays in millions of solicitations for bowel cancer screening and a backlog of individuals with positive screening awaiting further workup.
  • Repeated or extended lockdowns may reduce surveillance and advance care planning.
  • In the United States, there was an 86% reduction in preventive CRC screenings after March 1, 2020, a 64% decrease from previous years in number of colonoscopies performed between March 15 and June 16, 2020; and weekly volumes remained 36% lower thereafter compared with pre--COVID-19 levels.
  • To address these concerns, the American Society of Clinical Oncology, the European Society for Medical Oncology, and other professional societies established recommendations and guidance for cancer care during the pandemic and lockdowns.
  • To reduce risks for patients with gastrointestinal malignant neoplasms, the American College of Surgeons and other organizations set new priorities for CRC management, including prioritizing surgery for CRC involving imminent obstruction or locally advanced rectal cancer.
  • Early CRC diagnosis allows better treatment outcome.
  • A large meta-analysis showed that even a 4-week treatment delay was associated with increased mortality for 7 cancers, particularly CRC.
  • The investigators suggested that delays in CRC diagnosis would unnecessarily cost lives and life-years.
  • Strategies to minimize the clinical implications of delayed cancer diagnosis could include reinforcing mass screening using the fecal occult blood test, improving communication to avoid late patient diagnosis, and providing adequate resources and robust plans to deal with diagnosis and treatment backlogs.
  • Patient triage could include quick assessment of tumor burden and biomarker testing, particularly ctDNA.
  • Study limitations include lack of tumor volume assessment by imaging and inability to directly link tumor burden with care delays for newly diagnosed PANIRINOX participants.
  • The investigators described this as an exploratory study offering a snapshot of a situation that continues to evolve.

Clinical Implications

  • Patients diagnosed with mCRC after vs before the pandemic lockdown had increased tumor burden at diagnosis and lower survival.
  • CRC is a major area for intervention to minimize pandemic-associated delays in screening, diagnosis, and surgical treatment.
  • Implications for the Healthcare Team: Members of the healthcare team should promote preventative screenings as early CRC diagnosis allows for better treatment outcomes.

 

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