In the year 1918, there was influenza pandemic, wherein India had the largest number
of cases (10–20 million) among all the countries and had the highest case fatality
ratio (4.39%) worldwide.[1] The total magnitude of estimated deaths globally was 50–100 million. A mathematic
model predicted that if similar severity of influenza pandemic would have repeated
in 2004, the estimated mortality toll world over would have been 62 million, and with
a similar trend as in the past, nearly 14.8 million deaths were estimated in India
alone.[2], [3]
In the wake of a similar pandemic of COVID-19 causing chaos all around the world and
claiming thousands of lives, we need to introspect our current position and understand
our capacity to “bend the curve” to minimize the magnitude of damage at every cost.[4], [5] Fortunately, so far, the situation in India appears better in comparison to many
other countries, but the balance is dynamic. Cancer is a disease of the aging and
therefore, many of our cancer patients are old. Unfortunately, the severity of COVID-19
illness is also maximum in the elderly and those with comorbid conditions such as
uncontrolled hypertension or diabetes and cancer.[1] Hence, to reduce the impact of COVID-19, it is our joint responsibility as oncologists
to explicitly communicate our deficiencies, efficiencies, and the ongoing challenges
in treatment delivery and come to a consensus as a multidisciplinary team on where
we think is most appropriate to draw lines and decide on consistent treatment policies,
which are in alignment with the international guidelines, organization's capacity,
and safe practices.[2]
The great inventions in the medical fields of public health, critical care, and emergency
medicine such as vaccines, extracorporeal membrane oxygenation, several antibiotics,
antivirals, and targeted therapy have failed to cure critical patients suffering from
COVID-19, bolstering the ideology of “Prevention is still better than cure.”[3] Prevention of infection can only be achieved with population-based interventions
such as quarantine of the suspected, isolation of the infected, and social distancing
to reduce the cross contamination and improving hygiene to eventually “Flatten the
otherwise exponentially rising curve of the infected cases.”[4], [5] The ultimate goal is to control the pandemic globally and epidemic locally (the
strains of the viruses have been found to be different in different countries) by
developing of herd immunity but in a controlled manner so as to not overwhelm the
health-care sector.[6]
Execution of cancer care during the COVID-19 outbreak requires the oncologist to strike
a fine balance between selection of treatment that provides meaningful life years
and the treatment-related toxicities that make the patient more vulnerable to severe
infection of SARS-CoV-2, leading to avoidable mortality.[7] While it may still be comparatively easier for a multidisciplinary cancer care team
to come to a consensus on withholding standard treatments, this process becomes challenging
through involvement of patients in this decision-making to strike this fine balance.[8] A pandemic is a protracted dynamic event which can change the existing situations
by the day and that can be complicated by a variety of factors other than the virulence
such as the region's social, political, and ethical considerations.[9] Hence, the action plans that may be valid today may not hold in future and due cognizance
has to be paid to that uncertainty when deciding a road map.[9] Hospitals need to follow the new standards of care developed during the crisis and
provide room to adjust them based on the changing volume of patients and severity
of infection to successfully triage care.[4], [10], [11], [12], [13]
Cancer and COVID-19
The association of cancer and COVID-19 is multifaceted and so far, the limited evidence
suggests a higher case fatality rate in cancer patients (6%–20%) as compared to the
overall population (2%–3%).[1], [14], [15] There is a plethora of information on SARS-CoV-2 and cancer care guidelines during
the COVID-19 outbreak that are updating on a daily or weekly basis. Nevertheless,
local and regional factors such as logistics, infrastructure, socioeconomic and sociodemographic
structure of the population, the infection rate of the strain of SARS-CoV-2 specific
to that region, and the available resources are of paramount importance in adapting
guidelines to the different parts of a country.[7], [12], [13], [16], [17], [18], [19], [20], [21], [22] Despite this, there are several concerns for the patients as well as physicians
in delivering cancer care as follows:
Patient Concerns
These typically are the fear of the unknown, including that of cancer outcome, probability
of infection with coronavirus especially when stepping out for cancer treatment, interaction
between cancer and SARS-CoV-2 infection, and feeling more vulnerable due to cancer
diagnosis or its treatment.[23], [24] The other aspects are anxiety from possible adverse impact of delay in the institution
of therapy amidst the crisis and conflicts among patients' and caregivers' choice
including the criticality involved with people's end-of-life wishes in a resource-constrained
environment.[7], [8] Apart from these, a survey by the American Cancer Society (ACS) Cancer Action Network
showed that more than a quarter of the cancer patients were also worried about job
and insurance cover losses, causing difficulty in paying for the cancer treatments.
Because most of the cancer patients in India do not have health insurance cover, loss
of income would directly impact their out-of-pocket expenditure, further impacting
the health-care systems in India beyond the COVID-19 crisis.[25]
Concerns for Physicians
The physician concerns related to infection are the fear of working in a potentially
infectious and life-threatening environment with inadequate personal protective equipment
(PPE) and potentially increasing infection risk to family.[16] Other concerns are burnout related to long hours of work, shortage of staff as many
doctors infected at work get quarantined and a reserve pool needs to be available
to take over, rescheduled routines, disturbed sleep from constant psychological pressure
to treat patients with mostly noninvasive or supportive care measures, and deal with
the paradox of purposely delaying standard therapy even for cancers where overall
treatment time is directly correlated with outcomes.[7], [16], [19] These circumstances can lead to adverse cancer-related outcomes, potentially making
physicians vulnerable to litigation and physical violence.
Despite all the concerns, cancer care must continue whenever possible acknowledging
the risks associated with it during a COVID-19 outbreak. The following information
may be used to select treatments that may be considered safe and appropriate for different
cancers in the context of the COVID-19 crisis.[7], [13], [14], [15], [16], [17], [19], [26], [27]
-
Patient factors: The factors that make patients more vulnerable to severe COVID-19
and poor outcomes are extremes of age, uncontrolled chronic medical conditions such
as hypertension or diabetes mellitus, poor performance status, lower socioeconomic
status, no health insurance, lower education level, and poor support system
-
Tumor factors: These factors may help in prioritizing cancer therapies such as aggressive
versus indolent disease, presence of poor prognostic factors, disease potentially
threatening to vital organs, or disease progression that may lead to imminent life-threatening
event
-
Treatment-related factors: The treatment-related factors that need consideration prior
to selecting treatment modalities or initiating therapy are the intent and the expected
outcome, the potential effect of delaying standard therapy or using less aggressive
therapies, avoiding versus cautious use of intensive chemotherapy protocols which
may cause severe myelosuppression, and role of oral metronomic treatment to bridge
the gap. It is also equally important to ascertain the availability of infrastructure
for limiting cross-contamination in case of asymptomatic infected patients undergoing
therapy (as all patients on active cancer treatment will not be tested for infection
with SARS-CoV-2 at frequent intervals).
Whenever possible, triaging of patients should be done by a multidisciplinary team
and appropriate justification for the same should be documented for future reference
and medicolegal purpose. Both patients and physicians should be well versed with the
principles of prioritization.[22] Guidelines from the national oncological societies, the oncology peer groups, and
the local hospitals based on the international guidelines adapted to the local needs
are very helpful.[3], [10], [12], [13], [16], [19], [20], [21], [22], [26], [28] The NHS-UK takes into the account the probability of survival and potential benefit
from therapy and stratifies the patients into six groups. Treatment stratification
is by intent and is between curative and palliative, wherein the potential for successful
treatment, increasing lifespan, or palliation is graded from >50%, 15% to 50%, and
15%.[13] On the other hand, the French guideline also takes into account variables such as
age and cancer duration.[21] The ESMO Magnitude of clinical benefit is an objective tool and is worth using to
assess the potential benefit of treatment. It is advisable to use online calculators
for life expectancy or Cancer and Aging Research Group score for predicting toxicity
to provide objectivity in triaging therapy. Once the decision has been made on following
through with the treatment of the patient during the COVID-19 outbreak, the following
general measures can be practiced to avoid unnecessary contact and cross contamination.[3], [4]
[5], [12], [13], [14], [20], [21], [22], [26], [27], [28], [29], [30], [31], [32] During the COVID-19 outbreak, the decision to defer or alter standard therapies
even though based on international guidelines has to be carefully explained to the
patient along with its risks and uncertainties.
Pretreatment Workup and Counseling
Pretreatment Workup and Counseling
Patients can undergo necessary investigations at a center closer to home and visit
the cancer center only for consultation and treatment. Counseling prior to the therapy
whether by medical, surgical, or radiation team can be provided using telemedicine
units, video/conference calls, or by using prerecorded videos.[25] This ensures minimum contact while still providing all the necessary information
effectively. All staff involved in providing active treatment should be provided with
appropriate PPE, and utmost care should be taken to disinfect the therapy area before
using the facility or devices for the patients and in between patients to avoid inadvertent
cross contamination. 45 GSM basic PPE along with mask and gloves for all the housekeeping
and administrative staff; 70 GSM PPE with face shield, mask, and gloves for doctors
and therapy staff including nurses who come in direct contact of the patient; and
the advanced kit of 180 GSM for all intensive care unit (ICU) staff are considered
appropriate. However, details of PPE suitable for the setting, activity, and risk
of infection suitable for the India have been provided by the Directorate General
of Health services.[33] Despite all these measures, it is prudent to maintain social distancing in the patient
waiting areas, day-care facilities, near the pharmacy and billing departments, and
other areas within the hospital premises.
Principles for Choosing Appropriate Systemic Therapy
Principles for Choosing Appropriate Systemic Therapy
Wherever appropriate, de-escalation strategies should be executed such as avoidance
of intravenous route for systemic therapies as well as supportive care drugs and use
of oral or subcutaneous route such as oral metronomic chemotherapy and oral antibiotics
or antifungals and minimization of blood and platelet transfusions. Avoiding or cautious
use of intensive chemotherapy protocols with a propensity cause severe myelosuppression
or immunosuppression by means of specific T-cell suppression or B-cell immunomodulation
(e.g. bendamustine and fludarabine), or substitution with preferably oral metronomic
treatment to bridge the gap, may be opted. Use of single-agent checkpoint inhibitor
rather than dual therapy as in melanoma and other indications can reduce the toxicity
and cost of treatment.[34] At present, preemptive testing for COVID-19 in asymptomatic patients undergoing
chemotherapy is not universally recommended. First, there is no evidence that such
testing reduces either transmission to other patients or prevents COVID-19 disease
in patients undergoing chemotherapy. Second, the availability of tests is limited
and should be restricted to those individuals who merit testing as per the national
criteria.[35]
The therapy interval can be prolonged and less intensive (3- or 4-weekly regimens
instead of dose-dense 2-weekly regimens), prophylactic growth factor use may be encouraged,
and long-interval prescription refill should be provided to limit hospital visits.[12], [36] Because hydroxychloroquine and azithromycin are used for the treatment of severe
COVID-19, drugs such as anthracyclines, tyrosine kinase inhibitors, trastuzumab, and
anti-vascular endothelial growth factor agents notorious for QTc prolongation should
be used with due precaution and monitoring. Palliative intent treatment with good
disease control/stable disease can be given treatment holidays. Low-risk febrile neutropenia
may be managed on an outpatient basis and in local community clinics. Minimal investigations
between treatment cycles and response assessment should be done only when suspecting
progression.[10], [16], [18], [19], [34], [36], [37]
Principles to Guide Cancer Surgery
Principles to Guide Cancer Surgery
The calculus of risk–benefit ratio of cancer surgery has completely changed and become
far more complicated than it was due to the addition of a new dimension of risk of
infection and mortality by COVID-19. Two additional components that need to factored
into this already-complicated equation to decide appropriate surgery are the stage
of the epidemic that the local geographical area is in as that would require the health-care
facility to be available for the treatment of COVID-19 patients and the risk of exposure
of health-care worker.[38] The points that need to be considered while deciding for cancer surgery are the
need of surgery (stratified as emergency and lifesaving; urgent, if not done alters
outcome; and possible to delay in less aggressive early stages) and the type of surgery
(stratified based on the time taken to perform, days of hospitalization required in
the postoperative setting, overall risk of morbidity and mortality with the current
general condition, and comorbidity status).[13], [15] We recommend to continue performing simple surface surgeries such as the breast
and the thyroid, while elective aerosol-generating procedures that put all health-care
workers within the operating room, at risk are not encouraged. High-risk surgeries
especially in elderly patients are not recommended. When planned for surgery, it is
currently still not advisable to test all asymptomatic patients for COVID-19 as recommended
by the Indian Council of Medical Research. All the staff members handling the patients
are advised to use universal safety precautions and hand hygiene to avoid contaminating
the operation theater, recovery, and the ICU areas. Surgical oncology societies such
as the ACS and many others including the National Comprehensive Cancer Network (NCCN)
have suggested similar guidelines.[36], [38] The NCCN additionally mentions factoring in the time-sensitiveness of the procedure
and delaying the surgeries until the outbreak is controlled or till the time when
the health-care systems can be bolstered to deal with a sudden increase in COVID-19
patients wherever possible.[31]
Principles Guiding Radiation Therapy Decisions
Principles Guiding Radiation Therapy Decisions
Several radiation and oncology societies and our personal experience have shed light
on the judicious use of radiation during this outbreak, and broadly the following
principles should guide our decisions.[7], [12], [18], [28], [30], [31], [32], [36], [39] Priority should be given to patients that are at the end of their radiation therapy
(RT). All efforts must be focused on making the work environment safe for both the
patient and the radiation workers and therefore, it is important to minimize contact
by reducing the machine setup and treatment time. This can be achieved by limiting
the use of complex setups and treatment plans and also utilizing image guidance only
when considered necessary. Patients waiting for definitive RT especially for tumors
that are sensitive to overall treatment time should be treated on priority over those
waiting for RT. Indolent or hormone-responsive cancers such as hormone-responsive
luminal A type of early-stage breast cancer or hormone-responsive prostate cancer,
should be recommended hormonal therapy for 6–12 weeks until safe to resume RT services.[40], [41] It is recommended to defer RT where it produces no survival advantage except for
providing palliative care.[28], [31] Use of altered fractionation schedules such as hypofractionated UK-FAST and FAST
FORWARD regimen for breast cancer or SBRT for prostate cancer can greatly save machine
time and is strongly recommended. Similarly, altered fractionation may be used instead
of using radiosensitizing concurrent chemotherapy wherever appropriate.[40] These two measures may help reduce the number of fractions for head-and-neck and
breast cancers, which account for nearly 50% of the patients in the radiation department
in India. It is recommended to give priority to simple, short-course palliative treatment,
especially for distressing symptoms such as bleeding, severe pain, or dyspnea.
Brachytherapy which forms an integral part of treatment of cervical and endometrial
cancers should be strongly recommended. However, to minimize hospital visits, one
application with two treatments can be used provided it is dosimetrically safe. Pediatric
radiation treatments requiring daily anesthesia may be attempted under oral sedation
to minimize daily invasive procedure or greater machine time. Patients with preexisting
poor pulmonary functions/effort tolerance should not be recommended RT treatments
known to cause higher rates of radiation pneumonitis. These recommendations for both
the patients and healthcare workers are summarized in [Table 1].
Table 1
Summary of recommendations for patients and physician
|
For the patients
|
|
1. Social distancing and hand hygiene to be followed by all and at all times
|
|
2. Appropriate PPE to be donned by healthcare workers prior to coming in contact with
the patients
|
|
3. Patients on active treatment or symptomatic followup patients only should be seen
in the OPD
|
|
4. Maximize appropriate use of telemedicine and virtual tumor boards
|
|
5. Order only absolutely essential blood and other investigations
|
|
6. Choose the patients wisely by triaging based on age, comorbidity status, tumor
type, and risk of severe infection because of the therapy
|
|
7. Minimize therapies that increase the risk of cross contamination or ICU admission
such as head and neck surgeries and thoracic surgeries
|
|
8. Decrease the number of hospital visits by changing the treatment protocol whenever
possible, for example, using 3 weekly chemotherapy rather than weekly/2 weekly therapy,
changing radiation dose fractionation from daily to weekly, or by using shorter treatment
regimens
|
|
9. Avoid treatment that do not provide survival benefit but may increase the risk
of severe infection in patients
|
|
10. Offer palliative therapy judiciously, balancing the risk and benefits
|
|
11. Involve the patients and caregivers in the decision-making process when deferring
or altering standard therapies due to the COVID19 outbreak
|
|
12. If there is a risk of imminent death or severe disability due to progressive cancer,
continue treatment even if high risk
|
|
For healthcare workers
|
|
1. Use appropriate PPE as per standard national guidelines
|
|
2. Arrange centralized resource/website for adequate communication of the dynamic
policy decisions/guidelines with the evolving situation
|
|
3. Implement proper screening tools
|
|
4. Create clear stay at home and return to work guidelines
|
|
5. Ensure wellbeing and undertake measures and activities to reduce stress
|
While these guidelines were evolving, we had already started working toward producing
a safe environment for the cancer patients at Tata Memorial Centre. The initial experience
of adapting to the new working environment before and after the nationwide lockdown
has been summarized below.
Quest Prior to Lockdown
All the departments had to change the way things worked, and this affected the postgraduate
students, consultants, technologists, as well as ancillary staff. The focus in week
1 of the outbreak in India, before the nationwide lockdown, was to reduce the number
of patients that came to the hospital to minimize crowding and prevent opportunities
for virus transmission. This was accomplished by restricting patient entry in the
hospital more than 30 min prior to the appointment and providing quick follow-ups
including prescription refills and travel concessions for the asymptomatic patients
at the entry point of the hospital. All the follow-up patients with appointments for
the next 6 weeks were then systematically called for a telephonic follow-up by an
oncologist. Only those whom were felt to have symptoms warranting a hospital visit
were advised to do so. Thus, only patients on active treatment presented to the hospital.
Ordering imaging and other investigations (areas identified to have one of the highest
thoroughfares after the outpatient department [OPD]) were limited to be used for absolutely
essential indications and emergencies. Rather than giving less time per consult, these
restrictions made our OPD consultations longer and conversations more challenging.
Struggles during the Lockdown
Struggles during the Lockdown
The situation changed with the 40-day nationwide lockdown, which included suspension
of all means of public transport, allowing only very few patients within the city
to reach the hospital. Unlike other countries where public transport remained active,
a major challenge for our center was providing safe transport for the hospital staff
so that there was minimal disruption in the active treatment of patients. Fewer technicians
and ancillary staff forced us to reduce the overall numbers that were treated every
day, automatically leading to delay in therapy for most of the patients during the
lockdown. All elective aerosol-generating procedures were minimized, whereas surface
surgical procedures otherwise considered safe continued to be performed. Systemic
palliative and concurrent chemotherapy with higher risk–benefit ratios were deferred,
and adjuvant chemotherapy was postponed in most patients. Neoadjuvant chemotherapy
continued albeit with caution on intensity and interval between cycles on a case-to-case
basis. Instead of cytotoxic chemotherapies, less toxic regimens such as metronomic
schedules were practiced as appropriate.[22] Many patients have been called to report after the lockdown to start chemotherapy.
However, if there is further extension of the lockdown or India starts to experience
rapid community transmission of SARS-CoV-2, the future of systemic chemotherapy under
such circumstances may remain uncertain. Palliative treatment was being offered to
all the patients whenever indicated.
Preparedness for Longer Lockdown Duration
Preparedness for Longer Lockdown Duration
Because India has still not seen rapid community-wide transmission due to early lockdown,
one may hope for early return to normalcy. However, if it takes longer, then focus
should be on building capacity and re-organization of infrastructure to provide continuity
of care for the cancer patients. Quarantine and isolation facility for patients and
health-care workers need to be identified. Strict rotational duties should be implemented
to retain capacity to treat if some health-care workers need to be quarantined. Participation
in forming hospital networks such as the National Cancer Grid may help to form robust
referral base for future patients such that patients can continue to receive evidence-based
similar care. These networks can aid in collectively forming guidelines and pathways
to be followed for de-escalation of therapy and similarly chalk out a plan for exiting
these pathways when the outbreak comes under control. The short-term and long-term
outcomes of the patients treated during this period should guide in developing future
research protocols that can help during such pandemics or similar adverse situation.
Simple maneuvers such as continuing social distancing; omitting unnecessary human
contact; and practicing visage/universal precautions, infection control measures (e.g.
hand hygiene and cough etiquette), and nutritional diet, can help to conquer COVID
with “COVID.”[11] It is a tale of constant adaptation, auditing, revision, and change of cancer therapy
during the unprecedented COVID crisis. We not only are adapting to cope but to win!
