The ongoing COVID-19 pandemic is posing unique challenges to our health-care system.
Oncology practices and protocols are adapting to the situation to help our patients.
Head-and-neck squamous cell cancers are a huge burden in our country and need multidisciplinary
care. This document shares some pragmatic ideas for medical oncologists on how to
use systemic therapy for this disease in these challenging times.
The ongoing COVID-19 pandemic represents an unprecedented time in medicine and oncology
in particular. Both current and former cancer patients are at a greater risk of being
infected with COVID-19.[1],[2],[3] The rate of “severe events” (defined as admission to the intensive care unit, the
need for ventilation, or death) among cancer patients infected with COVID-19 exceeds
that of the noncancer patients.[1],[2],[3] The pandemic has added another layer of stress to cancer patients as there will
be significant disruptions in their planned treatment protocols and consequent care,
and things won't be normalized for quite sometime as per the statistical prediction
of this pandemic.
In this “new normal” situation, health-care systems are being stretched to the maximum
and the resources are being marshaled to provide good care to everyone, even though
the care may look different than the conventional standards. Every specialty is thinking
out of the box with innovative strategies adapted to the resource constraints and
abiding by the norms of lockdown and social distancing. Our medical oncology practice
has also been required to modify its pattern of care and bend around the established
standards of care, to provide solutions to our patients. In many cases, these may
be desperate measures without enough evidence backing them.
This novel rational model of care is based on the following key principles: (1) Does
the benefit of a particular chemotherapy cycle exceeds the risk of morbidity and mortality
from COVID-19? (2) Can we decrease the patient's hospital visits for the next few
weeks of lockdown? (3) Can we reduce the number of emergency visits for oncology patients,
as the emergency services are saturated and they may be triaged out? In simple words:
“Do not overburden the overstretched health-care system.”
Based on these basic principles, we have compiled some of our thoughts on how to manage
chemotherapy in head-and-neck cancer patients in this unforeseen situation. These
are neither guidelines nor consensus statements, rather our thoughts as a scientific
association, to provide a helping framework for the oncology community to adapt to
this unforeseen pandemic.
Head-and-neck cancers, especially squamous cell carcinoma (head-and-neck squamous
cell carcinoma [HNSCC]), is the most common cancer among Indian males, accounting
for 16.1% of cancer cases in them and accounted for 92,000 new cases in 2018.[4],[5] Worldwide, it is the 6th leading cause of cancer, with an annual incidence of 550,000 and death of 300,000
cases.[6] HNSCCs are highly aggressive malignancies with high recurrence rates among locally
advanced cancers even after curative therapy.[7] Surgery plays a major role in oral cavity and tongue cancers, whereas concurrent
chemoradiation is used for definitive therapy at most other sites. The role of chemotherapy
is restricted to concurrent chemoradiotherapy (CTRT) in adjuvant/definitive settings
and palliative chemotherapy for recurrent/metastatic settings.
Adjuvant and Definitive Chemoradiotherapy
Adjuvant and Definitive Chemoradiotherapy
Being highly aggressive cancers, it is imperative not to delay or compromise the adjuvant
CTRT or definitive CTRT, wherever indicated.[8] Accelerated radiotherapy may be considered to reduce the duration of treatment as
daily travel to cancer centers during lockdowns is a challenge. Cleaning and sanitization
of radiotherapy machines after each use is also recommended.
Only patients with absolute indications (positive margins and extranodal extension)
for adjuvant CTRT should be offered the same. Most cisplatin-eligible patients will
be fit without significant comorbidities, and hence, the benefits outweigh the risks.
The 3-weekly cisplatin (100 mg/m2) may be discussed in fit patients to minimize visits
to the day care, although this will not reduce the hospital footfall as the patients
will continue their daily visits for radiation. At most centers, oncologists may be
more comfortable with the weekly cisplatin of 40 mg/m2 schedule that requires fewer
hospitalization for toxicity. In platinum-ineligible cases, cetuximab, carboplatin,
and oral radiosensitizers such as capecitabine and hydroxyurea can be used with similar
results.[9],[10]
Neoadjuvant Chemotherapy
At many centers, elective surgeries for HNSCC are being postponed and as a time-buying
procedure, increased demand for neoadjuvant chemotherapy (NACT) has emerged. In discussion
with the multidisciplinary team, this needs to be explained to the patients and a
shared decision should be made. 1–2 cycles of NACT, two-drug, 3-weekly regimen (e.g.
paclitaxel + carboplatin/cisplatin + 5-fluorouracil), which is less toxic than the
three-drug regimen, may be used in this scenario.
Oral metronomic therapy (OMT) may be a novel bridge to surgery in smaller lesions.
However, this should be used very judiciously in consultation with the surgical team
as for smaller lesions, surgery remains the best curative option. The use of any therapy
in the neoadjuvant setting for HNSCC involves a risk of progression, which is not
desirable. Useful regimens include tablet methotrexate (15 mg/m2) + celecoxib[11],[12],[13] or the triple-drug metronomic regimen of erlotinib + methotrexate + celecoxib.[14] These regimens are effective with decent response rates and can halt stabilize tumor
progression for at least a few weeks to tide over the crisis. These are oral regimens,
can be taken at home without much-anticipated toxicity, perfectly complying with our
concerns in the pandemic.
Palliative Systemic Therapy
Palliative Systemic Therapy
Patients with fair performance status, tolerating palliative chemotherapy (± cetuximab),
may skip one/two sessions of chemotherapy after a mutual shared decision. For elderly
patients (>70 years) and those with significant comorbidities, single-agent cetuximab
and oral metronomic chemotherapy can be given. Patients on immunotherapy alone may
continue to receive, but at increased intervals (e.g. 4-weekly nivolumab instead of
2 weekly).[15] Those on chemoimmunotherapy may drop chemotherapy and continue with immuno-oncology
drugs for the next few weeks. Adverse effects among patients who receive immune checkpoint
inhibitors (such as for severe myocarditis and pneumonitis) are more challenging to
diagnose and might not be treated promptly, which might affect their survival. OMT
has a significant role in this setting. It is best suited for the elderly and patients
with comorbidities who have to be planned for a palliative regimen. Both double and
triple metronomic regimens mentioned above can be used based on the physician's discretion.
OMT may be used to tide over a few weeks in any patient awaiting palliative chemotherapy
or radiotherapy. These ideas are summarized in [Figure 1].
Figure 1 Algorithm for managing head‑and‑neck cancer chemotherapy during the COVID‑19 pandemic
Growth factors, such as granulocyte colony-stimulating factor, may be used less stringently
in elderly, frail patients or those with documented or anticipated toxicity in earlier
cycles.
Oral hygiene, hand hygiene, and cough etiquettes are extremely important for HNSCC
patients both on and off treatment, due to structural distortion of the aerodigestive
tract, compromised mucocutaneous barrier, Ryle's tube, etc., Regular mouthwash with
betadine and steam inhalation should be routinely advised and reiterated. A screening
questionnaire for the symptoms of COVID-19 may be used.
Telemedicine
We must consider postponing routine follow-up visits for patients not on active treatment
or use telemedicine. We need to interact with our patients and support and reassure
them emotionally while maintaining social distancing using technology. Video-calling,
virtual tumor boards using teleconferencing, emails, and chat messenger platforms
are important tools to be frequently used for consultation, report viewing, etc.,
Importantly, the telemedicine facility should be arranged with local public or private
cancer centers, minimizing patient's need to travel.
Examinations such as direct and indirect laryngoscopies are potential aerosol-generating
procedures. Oncologists should take the utmost protection while performing such procedures.
For HNSCC, whether or not to postpone cancer treatment, a decision needs to be made
on a patient-by-patient basis and according to the risk to the patient and the prevailing
situation. Delays could lead to tumor progression and ultimately poorer outcomes.
On the other hand, COVID-19 in an immunocompromised person can not only be more deadly,
but it can also derail chemotherapy treatments and invite more risks for the patient
and the health-care system. For each case, we should weigh what's more dangerous –
leaving the house or missing a chemotherapy treatment.
Finally, the situation is evolving rapidly, and recommendations are likely to change
as more evidence emerges specifically to oncology practice, patients with cancer,
and COVID-19.
