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Oncology for Doctors

Online Training and Research

The coronavirus COVID-19 pandemic outbreak (declared by WHO on 12th March 2020) has become an international emergency, likely to have long-lasting effects. In this ever evolving situation, cancer patients may suffer most as they are at high risk of severe infection due to immunosuppression treatment and mostly belong to above 65 years age group. Lock downs across the globe to contain the virus have severely affected care of cancer patients and could have caused delay in chemotherapy either due to restriction in movement or availability of Doctors & adequate Nursing care or fear of coming to hospital as they may acquire infection in the hospital.

The risks of high mortality in cancer patients with covid-19 are now while benefits for some chemotherapy / radiotherapy regimens may be there in future (adjuvant setting). This needs to be discussed with patients in detail.

In light of this unprecedented situation, the following recommendations have been formulated. These have been adopted from multiple international (NICE, ASCO, ESMO, ESTRO, ASTRO,NCCN, ESO, Tata Memorial Centre) recommendations released till date and will be reviewed on a regular basis. This is essential as current evidence indicates that patients with cancer have a very high mortality risk when they have COVID 19.

Broad Guidance

  1. Oncology specialist can be encouraged to develop a 5-7 days ROTA or as suitable to their specific work place so as to avoid multiple healthcare workers getting sick at same time
  2. Identify patients and categorized them to acute oncology and follow up patients. Acute oncology patients are those undergoing active chemotherapy and radiotherapy, targeted therapy or immunotherapy, those with hematological malignancy at any point of treatment, Post-transplant patient on immunosuppressive drugs and those who are Newly diagnosed with cancer and cancer of unknown primary
  3. Curative therapy : If benefit is less than 5%, increased risks with covid infection mitigate against the benefit . Reconsider the incremental benefit of any therapy you are initiating and the anticipated survival benefit. The incremental benefit must be weighed against the risk patients would incur by coming for treatment. Oral therapies should be favored when clinically appropriate.
  4. Palliative therapy : For patients with a poor performance status (2 and above) with solid tumours, most studies have shown no improvement in overall survival, consider withholding or deferring therapy. In patients with stage IV stable disease, consider treatment holiday for the following 4-8 weeks if feasible. Patients with severe symptoms / pain, short course radiation can be given.
  5. Consider switching to an oral option if feasible for chemotherapy (eg, replace 5FU with capecitabine)
  6. Chemoport flushing can be extended to 10 -12 weeks given the low level of evidence for frequent flushing.
  7. Decrease footfall in chemo daycare oncology department – no attendants and F & B team.
  8. Postpone all routine follow-up appointments
  9. Consider doing All clinics via virtual consults- preferably video.

GRADE ECOG PERFORMANCE STATUS

0 Fully active, able to carry on all pre-disease performance without restriction
1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
2 Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours
3 Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours
4 Completely disabled; cannot carry on any selfcare; totally confined to bed or chair

Checklist for chemotherapy at triage

  1. Does the patient have fever (temp >99) , cough, sore throat, nasal congestion, headache : Yes to any- escalate to consultant, not to enter the hospital. Consultant can assess to decide if likely COVID-19 or other reasons like expected febrile neutropenia
  2. Does the patient have a travel history abroad in the last 4 weeks ?
  3. Has the patient had an online review with the treating consultant before coming for chemotherapy (before each cycle) / radiotherapy (once a week)

Patient NOT to enter facility

If symptomatic (cough, fever and breathing difficulty ). Review in the flu clinic to be done and assessed for COVID testing. Primary consultant to be informed if COVID testing sent.

On Arrival at daycare or radiation facility

  1. No (prefer) or only one attendants allowed in the hospital for adult patients (If patient is wheelchair bound, consider deferring or stopping chemotherapy for this duration and switching to an oral option)
  2. Patient given gloves and mask at entry – to wear this throughout admission. This applies to patient attendant also.
  3. Change of clothes when in daycare
  4. Follow disposal guidance for mask, gloves and gown
  5. Social distancing (> 3 feet) and sit on alternate chairs.

Triage for Testing for COVID-19 for patients on chemotherapy

There is no evidence but the laboratory risk factors for COVID-19 are known with reports coming from various countries.

Risk factors for COVID -19 (adapted from MGH)

Epidemiological Vitals Labs
Age > 55
Respiratory rate > 24 breaths/min D-dimer > 1000 ng/mL
Pre-existing pulmonary disease Heart rate > 125 beats/min CPK > twice upper limit of normal
Chronic kidney disease SpO2 < 90% on ambient air CRP > 100
Diabetes with A 1c > 7.6% LDH > 245 U/L
History of hypertension Elevated troponin
History of cardiovascular disease Admission absolute lymphocyte count < 0.8
Use of biologics Ferritin > 300 ug/L

Patients to have the following tests done

Patients may be lymphopenic due to chemo or radiotherapy and may have a raised d-dimer . LDH can be non-specifically raised in cancer patients.

CBC, CRP, CPK, ferritin, LDH, D-dimer

If Absolute lymphocyte count <0.8
CRP more than X 2 ULN
Troponin-I more than x 2 ULN
D-dimer > 1000ng/ ml
Ferritin > 300 micgm/L (same as ng/ml) or raised levels
CPK more than x 2 ULN

If any two of the above are positive : patient may undergo COVID testing before presenting to the treating facility. Ideally, all patients to be tested for COVID before admission. If there is shortage of kits- the above may be considered.

Guidelines regarding Chemotherapy use

These are broad general guidelines. Each treatment decision has to be individualized with shared decision making between the patient and consultants.

Cancer Type Recommendations during COVID crisis

Breast Cancer Adjuvant / Neoadjuvant

  1. Consider proceeding to surgery (if COVID negative) rather than neoadjuvant therapy.
  2. If down-staging preferred for breast cancer, risk-benefit to be discussed and decision individualized.
  3. Change all weekly / dose dense to three weekly chemotherapy.
  4. Patients on three weekly chemotherapy will continue as per schedule.
  5. All patients will receive prophylactic pegylated GSF.
  6. Consider Lapatinib / Trastuzumab or trastuzumab alone in Her 2 positive pts currently without chemotherapy for the immediate 3 month period
  7. Consider 6 months of adjuvant trastuzumab if patients are ER positive and node negative.
  8. Consider oral Capecitabine for TNBC for the immediate 3 month period
  9. Substitute albumin-bound paclitaxel (Abraxane) for paclitaxel or docetaxel to reduce toxicity and potential for admission

Palliative

  1. Consider risks and benefits and consider commencing only if the benefits outweigh the risks.
  2. All patients who are on palliative chemotherapy should receive prophylactic pegylated GSF if they are insistent on continuing therapy

Head Neck Cancer Neoadjuvant

  1. For all non-nasopharyngeal cancers, neoadjuvant chemotherapy should be stopped and patients should be started on radiotherapy – this may be curative intent / palliative intent on a case by case basis.
  2. For nasopharyngeal cancers, neoadjuvant chemotherapy should be continued as before.

Palliative

  1. Consider risks and benefits and consider commencing only if the benefits outweigh the risks. For therapies with a median overall survival benefit of 2 months or less, the risks outweigh the benefits and such treatments should not be started until the pandemic in our region is resolved.
  2. All patients who are on palliative chemotherapy should receive prophylactic pegylated GSF if they are insistent.

Gynecological Cancers Definitive

  1. Concurrent CTRT is to be continued as per current practice. Be extra careful, with respiratory symptoms and exclude proactively prior to the next cycle.
  2. Consider Stopping maintenance bevacizumab.
  3. Give olaparib or other poly-ADP-ribose polymerase (PARP) inhibitors instead of chemotherapy plus maintenance PARP at first relapse for BRCA-positive PARP-naive patients to reduce admissions and risk of neutropenia

GU Renal Palliative

  1. Stop first-line immunotherapy using nivolumab with ipilimumab in intermediate and poor risk groups, & switch to either first-line single agent nivolumab or use oral therapy as first-line and nivolumab with ipilimumab as second-line therapies to reduce toxicity
  2. Use first- and second-line oral tyrosine kinase inhibitors and switch nivolumab from second- to third-line to delay use of IV immunotherapy.

GU Prostate Palliative

  1. Consider risks and benefits and consider commencing only if the benefits outweigh the risks.
  2. All patients who are on palliative chemotherapy should receive prophylactic pegylated GSF if they are insistent.
  3. Prioritise enzalutamide/abiraterone upfront with ADT rather than docetaxel

CNS Definitive

  1. Conurrent temozolamide should be continued as per scheduled with appropriate prophylaxis.
  2. Adjuvant TMZ and PCV to be continued and started as per schedule.
  3. Limit TMZ in GBM to 6 cycles post concurrent CRT as per STUPP protocol.

Palliative

  1. Defer salvage chemotherapy for 4 weeks with supportive medical decompression as required.

GI Rectum Neoadjuvant

Do not start new patients on NACTRT. As per RT guidelines to be started on SHORT regimen. Short course radiotherapy followed by a delay of surgery 6-8 weeks later.

GI GOJ/ Gastric Early / Neoadjuvant

Consider upfront surgery followed by CLASSIC Cape-Ox chemotherapy

GI Anal Canal Definitive

  1. To start on Capecitabine and Mitomycin with radiotherapy. Mitomycin to be started on case to case basis.

GI CRC Palliative

  1. Consider risks and benefits and consider commencing only if the benefits outweigh the risks. For therapies with a median overall survival benefit of 2 months or less, the risks outweigh the benefits and such treatments should not be started until the pandemic in our region is resolved.
  2. No maintenance Bevacizumab or regorafenib (oral but can lead to emergency visits due to side effects)
  3. Allow intermittent treatment with chemotherapy regimens that contain cetuximab or panitumumab to reduce the need for immunosuppressive treatment

GI-NEN Palliative

  1. Consider oral temozolomide and capecitabine instead of intravenous therapy
  2. For dotascan positive patients, consider octreotide LAR rather than PRRT till the pandemic resolved.

GI Pancreas Definitive / Palliative

  1. Do not start patients as benefits are small. For therapies with a median overall survival benefit of 2 months or less, the risks outweigh the benefits and such treatments should not be started until the pandemic in is resolved.

Lung Definitive

  1. If CT RT is started, then paclitaxel and carboplatin is the preferred regimen.

Palliative

  1. Defer new palliative chemotherapy if possible.
  2. For patients with urgent indications for chemotherapy case by case decisions on the appropriate regimen and drugs should be taken with emphasis on choosing less hematotoxic regimens.
  3. Defer chemotherapy by 4 weeks for patients ongoing palliative chemotherapy
  4. Stop maintenance pemetrexed in combination with pembrolizumab to reduce treatment toxicity and risk of neutropenia
  5. Consider pembrolizumab to be given as a single agent as a first-line treatment for squamous or non-squamous NSCLC and a PDL-1 score of less than 50% to reduce treatment toxicity and risk of neutropenia
  6. Allow durvalumab be given 4 weekly in patients eligible for durvalumab following treatment with chemo- radiotherapy to reduce the number of hospital visits
  7. Switch to carboplatin and paclitaxel from day 8 treatments such as gemcitabine
  8. Stop first-line chemotherapy for stage IV SCLC after 4 cycles to reduce hospital admission and risk of neutropenia

NHL Definitive

  1. Treatment to be initiated promptly. R-CHOP continues to be the standard of care for diffuse large B-cell lymphoma, with DA-EPOCH-R indicated only for double-hit and primary mediastinal B-cell lymphomas.
  2. For older patients, R-mini-CHOP with growth factor support is recommended.
  3. Patient with High risk of CNS involvement IT methotrexate may be considered
  4. For limited stage disease, R-CHOP X 4 rather than combined modality therapy is recommended.
  5. Avoid auto-transplants in the current scenario.
  6. Outpatient regimens are preferred when possible and are an alternative for non-transplant eligible patients as well.
  7. If outpatient chemotherapy can be used to delay HDC/auto SCT then it should be encouraged. Oral lenalidomide and bendamustine are an option
  8. Suspend subcutaneous rituximab maintenance to avoid patients attending hospital
  9. Suspend subcutaneous obinutuzumab maintenance to avoid patients attending hospital.

Myeloma

  1. Consider oral pomalidomide with dexamethasone as second- or third-line therapy instead of IV treatments in patients previously treated with lenalidomide.
  2. Consider first-line lenalidomide and dexamethasone for transplant eligible patients in preference to regimens that require more hospital attendances
  3. Consider second-line lenalidomide and dexamethasone for patients who have not been previously treated with bortezomib.

CRC: colorectal cancer; NEN: neuroendocrine neoplasia; CTRT: chemoradiotherapy ; SCLC: small cell lung cancer; NSCLC : non small cell lung cancer.

 

References:

  1. Liang, Wenhua, Weijie Guan, Ruchong Chen, Wei Wang, Jianfu Li, Ke Xu, Caichen Li, et al. 2020. “Cancer Patients in SARS-CoV-2 Infection: A Nationwide Analysis in China.” The Lancet Oncology 21 (3): 335–37.
  2. National Health Services. 2020. “Clinical Guide for the Management of Cancer Patients during the Coronavirus Pandemic,” March. https://www.england.nhs.uk/coronavirus/wp-content/uploads/sites/52/2020/03/Specialty-guide_Cancer-and-coronavirus_17-March.pdf.
  3. MGH COVID-19 treatment guidance
  4. https://www.nice.org.uk/guidance/ng161/resources/interim-treatment-change-options-during-the-covid19-pandemic-endorsed-by-nhs-england-pdf-8715724381