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ESMO management and treatment adapted recommendations in the COVID-19 era: Colorectal cancer (CRC)

The tiered approach of ESMO in delivering a guidance for cancer patients during the COVID-19 pandemic is designed across three levels of priorities, namely: tier 1 (high priority intervention), 2 (medium priority) and 3 (low priority) – defined according to the criteria of the Cancer Care Ontario, Huntsman Cancer Institute and ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS), incorporating the information on the value-based prioritisation and clinical cogency of the interventions

  • High priority: Patient's condition is immediately life threatening, clinically unstable, and/or the magnitude of benefit qualifies the intervention as high priority (e.g. significant overall survival [OS] gain and/or substantial improvement in quality of life [QoL]);
  • Medium priority: Patient's situation is non-critical but delay beyond 6 weeks could potentially impact overall outcome and/or the magnitude of benefit qualifies for intermediate priority;
  • Low priority: Patient's condition is stable enough that services can be delayed for the duration of the COVID-19 pandemic and/or the intervention is non-priority based on the magnitude of benefit (e.g. no survival gain with no change nor reduced QoL).

 

Priorities for CRC patients

Outpatient visit priorities

High Priority

  • Potentially unstable (acute abdominal pain, intestinal occlusion, ascites, complications after surgery/endoscopy or radiological interventions, diarrhoea, severe skin toxicity, new symptoms, clinical progression)
  • Symptomatic new patients (symptomatic ascites, intestinal occlusion, chronic diarrhoea)

Medium Priority

  • Newly diagnosed asymptomatic patients, no prior surgery
  • Newly diagnosed asymptomatic patients after surgery for treatment strategy planning in case of adjuvant and first-line treatment 
  • Chemo/radiotherapy-related serious side effects
  • Established patients with new problems or symptoms from treatment – convert as many visits as possible to telemedicine appointments

 Low Priority

  • Second opinion
  • Secondary prevention of CRC; if possible, schedule blood tests and imaging close to home and convert to telemedicine
  • Follow-up visit out of study
  • Re-staging in metastatic setting when the goal is not to perform surgery with curative intent on metastatic and primary lesions
  • Re-staging in third- and fourth-line treatment
  • Follow-up visit on maintenance treatment; if possible, schedule blood tests and imaging close to home and convert to telemedicine

Priorities for CRC: Imaging and radiological/endoscopic interventions

High Priority

  • Radiological confirmation of intestinal occlusion, bleeding, perforation, post-surgical complications and post-interventional procedures
  • Radiological confirmations of bone fractures due to metastasis

Medium Priority

  • Diagnostic imaging/endoscopy for clinically-suspected CRC (clinical, biomarkers, family history)
  • Diagnostic imaging/endoscopy for high-risk categories (familial cases of CRC, serrated polyps)

Low Priority

  • Secondary prevention of CRC, prefer to perform occult test; if possible, schedule blood tests and imaging close to home and convert to telemedicine
  • Follow-up visit out of study
  • Re-staging in metastatic setting when the goal is not to perform surgery with curative intent on metastatic and primary lesions
  • Re-staging in third- and fourth-line treatment

 Priorities for CRC: Surgical oncology

High Priority

  • Radiologically-confirmed intestinal occlusion in newly diagnosed patients
  • Bowel perforation, peritonitis
  • Massive gastrointestinal bleeding
  • Post-surgical complications (perforation, anastomotic leak)
  • Post-colonoscopy complications (perforation, bleeding)
  • Post-interventional procedure such as liver and lung biopsies (perforation, organ damage, peritonitis, abscess, massive bleeding)
  • Bone fractures with spinal cord compression due to metastasis

Medium Priority

  • Clinical stage I, II and III colon cancer
  • Clinical stage I rectal cancer
  • Clinical stage II-III rectal cancer after neoadjuvant treatment
  • Resection of metastasis in oligometastatic patients with curative intent as front line or after neoadjuvant treatment

Low Priority

  • Early stage rectal cancer after complete radiological response following radiotherapy (watch-and-wait strategy)
  • Prophylactic surgery – for familiar cases of CRC
  • Biopsy of metastatic lesions for molecular analysis for late-line treatments. Start last-line options and wait until the end of the COVID-19 pandemic for such evaluation. When possible, use liquid biopsies for such analyses rather than biopsies

 Priorities for colon cancer: Medical oncology  Early colon cancer

High Priority

  • Severe complications due to the treatment (surgery, radiation, chemotherapy) that require hospitalisation. Avoid outpatient visit appointments and plan with the medical staff, after triage, admission to the ward

Medium Priority

  • Adjuvant treatment for high-risk stage II patients
  • For stage II patients, molecular testing for MSI and DPD are suggested for treatment decisions 
  • Adjuvant treatment for low- and high-risk stage III patients. Consider applying capecitabine in combination with oxaliplatin in place of infusional 5-FU. Moreover consider, based on the IDEA trial recommendations and based on oxaliplatin-related side effects, administration of treatment for 3 instead of 6 months

Low Priority

  • Weekly blood tests unless clinical conditions and symptoms require them
  • Radiological evaluation by considering the patient's risk/benefit ratio 

 Priorities for rectal cancer: Medical oncology  Early rectal cancer 

High Priority

  • Severe complications due to the treatment (surgery, radiation, chemotherapy) that require hospitalisation. Avoid outpatient visit appointments and plan with the medical staff, after triage, admission to the ward

Medium Priority

  • Neoadjuvant/adjuvant treatment for stage II and III patients
  • Continuation of a treatment in the context of a clinical trial

Low Priority

  • Weekly blood tests unless clinical conditions and symptoms require them
  • Radiological evaluation by considering the patient’s risk/benefit ratio

 Priorities for colon cancer: Medical oncology – Advanced CRC

High Priority

  • Severe complications due to the treatment (surgery, radiation, chemotherapy) that require hospitalisation. Avoid outpatient visit appointments and plan with the medical staff, after triage, admission to the ward

Medium Priority

  • First-line treatment for patients with PS 0-2 (ECOG scale) with the goal of reducing symptoms
  • First-line treatment for patients with PS 0-2 (ECOG scale) with the goal of reducing the tumour bulk and performing curative surgery
  • First-line treatment for patients with PS 0-2 (ECOG scale) who quickly relapsed after adjuvant treatment
  • Second-line treatment for patients with PS 0-2 (ECOG scale) after short PFS1
  • Second-line treatment with immunotherapy for MSI-H mCRC patients
  • Continuation of treatment in the context of a clinical trial

Low Priority

  • Delay all treatments with modest benefit expected, maintenance therapy and treatments in patients with low disease burden and slow progression
  • Delay all treatment including first line for patients with PS 3 and heavy comorbidities
  • Delay all treatments for those patients who had severe complications also during the adjuvant therapy
  • Delay all treatment for symptomatic slowly growing recurrent disease

 Priorities for CRC: Radiation oncology 

High Priority

  • Severe complications due to the disease progression (compression with organ failure, bleeding, pain, fractures, mediastinal mass with symptoms of compression, symptomatic brain metastases). Avoid outpatient visit appointments and plan with the medical staff, after triage, admission to the ward

Medium Priority

  • Neoadjuvant/adjuvant treatment for stage II/III rectal cancer
  • SIRT for patients with oligometastatic disease for which systemic treatment is contraindicated

Low Priority

  • Delay all treatments with modest benefit expected, for symptomatic slowly growing recurrent disease and for patients with low disease burden and slow progression

Chemotherapy in in early stage (II, III) colon cancer

  • Test for MSI-especially for stage II patients for treatment decisions
  • If possible, we recommend clarifying the DPD status in order to adapt the doses of capecitabine
  • Prefer the use of capecitabine over infusional 5-FU
  • Based on the IDEA trial recommendation, assess whether 3 months of adjuvant treatment will be non-inferior to 6 months of treatment (patient risk and clinical conditions-adapted strategy)
  • Avoid weekly blood tests, unless signs of infection and complications are present
  • Consider using telemedicine for weekly monitoring of the side effects and dose adaptations
  • Before admitting the patient for the next infusion of oxaliplatin, consider performing blood testing near home and use telemedicine to evaluate if a delay in the cycle administration needs to be applied
  • For patients with recurrent neutropaenia, consider the use of G-CSF to reduce the risk of febrile neutropaenia and hospitalisation

Chemotherapy in advanced stage (IV) CRC

  1. First-line treatment
    • FOLFOXIRI +/- anti-VEGF or anti-EGFR: consider administering the treatment in the outpatient clinic and provide the maximum support to prevent side effects; consider the application of pegfilgrastim in higher-risk patients to prevent febrile neutropaenia and hospitalisation
    • FOLFIRI or FOLFOX +/- anti-VEGF or anti-EGFR: consider administering the treatment in the outpatient clinic and the application of pegfilgrastim in higher-risk patients to prevent febrile neutropaenia and hospitalisation, in particular for patients with comorbidities and history of chemotherapy-induced neutropaenia
    • Anti-EGFR in combination with either FOLFIRI or FOLFOX: consider administering the treatment in the outpatient clinic in a 2-week interval rather than 1-week interval for cetuximab. Alternatively, discuss the use of panitumumab
  2. Second-line treatment
    • For patients with slow progression/growth consider administering the treatment every 2 weeks. If not possible due to toxicity and slow recovery, consider administering the treatment every 3 weeks
  3. Maintenance therapy
    • When indicated, a 3-week interval should be considered. Consider administration of capecitabine instead of infusional 5-FU
  4. Third-line treatment with regorafenib and TAS-102
    • Consider the use of telemedicine for weekly control of the side effects. Blood tests may be performed close to home

Radiotherapy for early stage rectal cancer

  • Consider administering short course radiotherapy (5 x 5) +/- capecitabine instead of long course radiotherapy
  • When a combinational chemotherapy with oxaliplatin is planned, consider administering capecitabine instead of infusional 5-FU

List of abbreviations: 5-FU, 5-fluorouracil; COVID-19, severe acute respiratory syndrome coronavirus 2-related disease; DPD, dihydropyrimidine dehydrogenase; ECOG, Eastern Cooperative Oncology Group; EGFR, epidermal growth factor receptor; FOLFIRI, folinic acid/5-fluorouracil/irinotecan; FOLFOX, folinic acid/5-fluorouracil/oxaliplatin; FOLFOXIRI, folinic acid/5-fluorouracil/oxaliplatin/irinotecan; G-CSF, granulocyte colony-stimulating factor; mCRC, metastatic CRC; MSI, microsatellite instability; MSI-H, microsatellite instability-high; PFS1, first progression-free survival; PS, performance status; SIRT, selective internal radiotherapy; TAS-102, trifluridine/tipiracil; VEGF, vascular endothelial growth factor.

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