Keywords
anticancer treatment - cancer care - coronavirus - COVID-19 - impact - retrospective
study
Dr. Rajesh Patidar
COVID-19 Outbreak Overview
COVID-19 Outbreak Overview
Coronavirus disease 2019 (COVID-19) pandemic has present new challenges for us to
live with, as there is currently no proven vaccine or drugs that will effectively
prevent or treat COVID-19 infection. There has been a reluctance of patients to visit
hospitals and clinics and thus delay the screening or treatment in fear of development
of COVID-19 and potentially succumb to the disease. This is especially true with elderly
patients as they have high risk factors (diabetes, heart problems, and hypertension)
and immunosuppressed patients.[
1
] The reduced availability of fundamental services such as diagnostic tests, surgeries
(with predicted hospital overloaded with COVID-19 patients), and shortage of expert
staff leading to lack of proper treatment, monitoring, and follow-up. The clinical
presentation of COVID-19 is heterogeneous and a large proportion of the patients are
asymptomatic. The scenario is even more intricate in cancer patients, as manifestations
of the tumor and side effects of the treatment might mimic COVID-19.[
2
]
[
4
]
Preliminary data from China reports that the case fatality rate (CFR) for COVID-19
affected cancer patients is approximately double than that for COVID-19 affected general
population (5.6% vs. 2.3%).[
5
]
[
6
] Although this pandemic has massively spread worldwide, the impact on cancer patients
is still largely unknown. Currently, there are only few retrospective reports published,
including a small number of subjects on active anticancer treatment and suggesting
that cancer patients might be prone to develop severe presentations of COVID-19. India
is the second most populous country, with geographical and ethnic variation, various
institute in India has formulated their own guidelines suitable for the population
they cater.[
7
]
[
8
] In this period of uncertainty, these very preliminary data could induce physicians
to abstain from life-saving treatments in fear of the risk of infection. As one of
the tertiary care centers for oncology in central India, we would attempt to delineate
a comprehensive picture of our experience, CFR, and adaptations that were made to
tackle this situation.
Methods
Data of all the patients who received chemotherapy and other systemic therapies in
the Department of Medical Oncology at Sri Aurobindo Institute of Medical Sciences,
from March 23,2020 to August 15, 2020 were retrospectively analyzed. We identified
patients with a confirmed diagnosis of COVID-19, defined according to the World Health
Organization (WHO) criteria, with a positive real-time polymerase chain reaction (RT-PCR)
assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on a nasopharyngeal
swab. Demographic, clinical, and treatment characteristics of the patients were retrieved
from the medical records and from our institution’s archiving systems.
Results
Considering the index period (March 23–August 15, 2020), 4,494 confirmed cases of
COVID-19 were admitted at our institute. In the department of medical oncology out
of 578 patients presented to the outpatient department, 291 patients were admitted
for active treatment. During admission all the patients underwent mandatory screening
for COVID-19 by RT-PCR assay, of which 23 cases were diagnosed with laboratory-confirmed
COVID-19, which constitutes approximately 0.51% of the total cases. However, the infection
rate among the patients with cancer seems to be higher 7.9% (23 out of 291 cases).
Similarly, total mortality among COVID-19 positive cases was 3.6% (162 death out of
4,494) with the mortality rate recorded among the cancer patients with COVID-19 was
13% (3 deaths/23). Details are summarized in [Table 1].
Table 1
Details regarding the COVID-19 patients
|
SAIMS COVID-19 hospital
|
Number of cases (from March 23 to August 15, 2020)
|
|
Abbreviations: COVID-19, coronavirus disease 2019; SIAMS, Sri Aurobindo Institute
of Medical Sciences.
|
|
Total COVID-19 patients hospitalized
|
4,494
|
|
Total COVID-19 deaths reported
|
162
|
|
Total cancer patients with COVID-19 hospitalized
|
23
|
|
Total cancer patients with COVID-19 deaths reported
|
03
|
|
Total mortality 3.6%
|
Mortality among cancer patients 13%
|
Median age was 40 years and the majority of patients were male (60%). The most common
cancer type was acute lymphoblastic leukemia (ALL) presented at various stages of
treatment, totaling 21.7% (5/23). Fifty percent (6/12) of patients with solid malignancies
(other than hemato–lymphoid) have presented with stage IV disease. Thirty-four percent
patients had associated comorbidities like hypertension, diabetes mellitus, cerebrovascular,
cardiovascular, pulmonary, and hepatic diseases, the most common being diabetes mellitus
(17%).
Out of three deceased, one patient (age 45) had good performance status and received
high dose consolidation for acute myeloid leukemia (AML) (diagnosed with COVID-19
within 14 days of chemotherapy), the second patient (age 30) was on palliative treatment
for metastatic carcinoma of the rectum and had poor performance status (Eastern Cooperative
Oncology Group Performance Status = 3), and the third patient was a newly diagnosed
elderly AML (age 60) Details of the patient's characteristics mentioned in [table 2].
Table 2
Demographic and baseline clinical characteristics of COVID-19 infected cancer patients
|
Abbreviation: COVID-19, coronavirus disease 2019.
Note: Data are presented as n (%) unless noted otherwise.
aTreatment after the diagnosis of cancer.
bTime from last antitumor treatment to diagnosis of COVID-19.
|
|
Characteristic patients (N = 23)
|
|
Median age (interquartile range), y
|
40 (28.0–65.0)
|
|
Male sex
|
14 (60.8)
|
|
Tumor diagnosis
|
|
Acute lymphoblastic leukemia (ALL)
|
5 (21.7)
|
|
Acute myeloid leukemia
|
3 (13.0)
|
|
Hodgkin’s lymphoma
|
1 (4.3)
|
|
Low grade lymphoma
|
1 (4.3)
|
|
Ovarian cancer
|
3 (13.0)
|
|
Lung cancer
|
1 (4.3)
|
|
Colon cancer
|
2 (8.6)
|
|
Rectum cancer
|
2 (8.6)
|
|
Liver cancer
|
1 (4.3)
|
|
Breast cancer
|
1 (4.3)
|
|
Multiple myeloma
|
1 (4.3)
|
|
Osteosarcoma
|
2 (8.6)
|
|
Tumor stage
|
|
Stage I/II/III
|
6 (26.0)
|
|
Stage IV
|
6 (26.0)
|
|
History of prior treatment
|
|
Chemotherapya
|
21 (91.3)
|
|
Chemotherapy (< 14 d)b
|
18 (78.2)
|
|
Surgeryb
|
5 (21.7)
|
|
Source of infection
|
|
In community
|
17 (74.0)
|
|
Nosocomial transmission
|
6 (26.0)
|
|
Comorbidities
|
|
Diabetes
|
4 (17.3)
|
|
Chronic cardiovascular and cerebrovascular disease (including hypertension and coronary
heart disease)
|
2 (8.6)
|
|
Chronic pulmonary disease (including chronic obstructive pulmonary disease and asthma)
|
1 (4.3)
|
|
Chronic liver disease (including hepatitis B and cirrhosis)
|
1 (4.3)
|
|
Symptoms and signs on admission
|
|
Fever
|
17 (73.9)
|
|
Cough
|
6 (26.0)
|
|
Dyspnea
|
4 (17.3)
|
|
Myalgia and fatigue
|
10 (43.4)
|
|
Death
|
3 (13.0)
|
All the positive cases were periodically evaluated also by the colleagues of pulmonary
and anesthesiology departments and the majority were treated with hydroxychloroquine,
antiviral drugs, and azithromycin; none of our patients received tocilizumab. Three
patients (13%) developed severe disease (defined as necessity of high-flow supplemental
oxygen) and were supplemented by oxygen and subsequently by continuous positive airway
pressure. None of our patients were offered invasive ventilation, due to the absence
of indication attributable to prognosis. Eighty-seven percent (20/23) patients were
discharged after full clinical recovery and negative RT-PCR on a nasopharyngeal swab.
Discussion
Out of 291 patients admitted in our department, 23 patients had laboratory-diagnosed
COVID-19. Median age was 40 years (28–65 years), similar analysis done by Ramaswamy
et al showed that the median age at presentation was 42 years[
9
] and by Mehta et al where the median age was 52 years.[
10
] This median age at presentation is way less when compared with other countries like
China, where Liang et al[
6
] (63 years) and Zhang et al[
11
] (65 years) have concluded that the infection is more in advanced age group cancer
patients. The possible reason for this discordance could be: first, younger age at
diagnosis of cancer in our population; second, older age group patient was strictly
not allowed to come out of home during lockdown, and hence, could not attend the hospital;
and third, approximately 60% of our population is less than 35years of age. Sixty
percent patients were male, which is similar to the report by Mehta et al[
10
] (56%), Ramaswamy et al[
9
] (54%), and Zhang et al[
11
]from china (60%). Most common cancer seen in COVID-infected cancer patients was ALL,
similar to that reported by Ramaswamy et al[
9
] (20%) and Mehta et al[
10
] (17.7%), whereas lung cancer was most common in studies done by Liang et al[6] and Zhang et al.[11] Six (26%) of them presented with stage IV disease.
The infection rate among the patients with cancer was 7.9% (23 out of 291 cases) which
was similar in comparison to other tertiary care institute in India, where positivity
rates were 6 (Mehta et al)[
10
] and 3.4% (Ramaswamy et al).[
9
] On comparison with China, where Zhang et al[
11
] reported a positivity rate of 2.2%. As both countries are densely populated, still
the incidence rate of COVID-19 in cancer patients from China was lesser, the cause
behind it could not be ascertained and should be investigated with larger study population
in our scenario.
Mortality rate in COVID-infected cancer patients was higher (13%) in comparison with
general population (3.6%). However, the high proportion of risk factors for severe
disease (age, comorbidities, immunocompromised state, and anticancer therapy) among
our patients must be considered. CFR in other hospitals of India was 14.2 (Mehta et
al)[
10
] and 10% (Ramaswamy et al).9
In a large case series of 72,314 patients published by the Chinese Center for Disease
Control and Prevention (CDC),[
5
] the case fatality in general population was around 2.3%, and in patients with a
history of malignancy, it was 5.6%. The WHO China Joint Mission on COVID-19 reported
a CFR of 7.6% for cancer patients. Zhang et al[
11
] reported a very high mortality rate of 28%.
The most common symptom at admission was fever (n = 17, 74%), followed by fatigue and myalgia (n = 10, 43%) and cough (n = 6, 26%). Only three patients (13%) developed severe disease and required supplemental
oxygen therapy and finally succumbed. Symptoms resolved in all the survived patients,
obtained RT-PCR assay clearance, and were transferred to oncology wards in good general
condition for the continuation of anticancer therapy. The results of our study are
more or less consistent with the review of literature on outcomes of cancer patients
with COVID-19 published by Sharin et al.[
12
]
It was also noted that 26% of our patients have developed COVID-19 infection during
hospitalization and nosocomial transmission of SARS-CoV-2 was suspected. Hospital-related
transmission has been reported in both patients[
13
] and health care workers. In a retrospective case study by Wang et al[
14
] with 138 patients, 41.3% of the patients were reported to have acquired COVID-19
infection during hospitalization, and of these, 5 patients were from the oncology
department. Nationwide statistics of the Chinese CDC confirmed COVID-19 transmission
within patients in health care settings.[
5
] Therefore, health care facilities need to reemphasize the importance of basic infection
control measures to combat the spread of contagious pathogen via respiratory droplets.
Seventy-eight percent of the COVID-19-acquired cancer patients have received antitumor
chemotherapy within past 14 days of diagnosis of COVID. However, delaying antitumor
treatment cannot be recommended as a reasonable choice to reduce the infection risk
in the ongoing pandemic. Cancer patients should receive antitumor treatment in the
setting of vigorous screening for COVID-19, including chest computed tomography scan
and RT-PCR testing, and the same should be extended to their companions.
Adaptations Done at our Center to Continue Cancer Care
Adaptations Done at our Center to Continue Cancer Care
-
In aggressive cancers like ALL and AML where delaying the treatment is associated
with poor outcomes or fear of relapse, de-escalation strategies were executed such
as avoidance of intensive therapy and use of oral metronomic chemotherapy, and minimization
of blood and platelet transfusions.
-
Increasing duration between chemotherapy cycles (three weekly instead of weekly).
-
Use of colony-stimulating factors to decrease the risk of neutropenia helped to tackle
this situation.
-
Promoting home-based chemotherapy or with nearby centers with shared care with primary
physician.
-
In COVID-19 positive cancer patients, palliative intent systemic chemotherapy, elective
surgeries, and radiotherapy planning were postponed until full clinical recovery and
repeat negative RT-PCR on swab.
We strongly recommend the continuation of anticancer treatment by endorsing consistent
preventive measures, mitigating some concerns previously expressed. We suggest considering
the risk of severe infection on a case-by-case basis and balancing it with the harm
that could be created by treatment delay or interruption.
Limitations
Our findings support the vulnerability of cancer patients in the current pandemic.
However, the limits of our study must be acknowledged. The study was retrospective,
nonrandomized, and based on a small sample size. The tumor types were diverse, and
heterogeneity could not be avoided.
Conclusion
Cancer patients affected with COVID-19 have worse outcomes when compared with the
general population; hence, they should undergo vigorous screening and intensive surveillance.
Anticancer treatment during COVID-19 should be altered according to the type and prognosis
of cancer. Fear of COVID infection risk should not divert the physician from the urge
to treat the patients, particularly when a curative option is considered and if a
delay could reduce its efficacy. In this setting, the dread of a possible threat should
not doom to a certain debacle.
