If so, for how long would you expect this increased susceptibility to last? Our medical oncologists often tell patients that their lymphocyte counts may be compromised for up to 6 months after chemotherapy and therefore may be at increased risk for viral infections during that time.
"May you live in interesting times" (purported Chinese curse). Right now we are adding a new element to our thoughts on therapeutic ratio for patients. This will depend on so many variables including patient age, her/his underlying comorbidities, the density of COVID infections in your city, the status of your department's work force, patient preferences....and most importantly the severity and curability of your patient's malignancy. We don't want patients to die as a consequence of our anxiety (but these should be counted in a COVID death rate IMO).
The data on the rate of cytopenias with thoracic radiotherapy is pretty limited in the absence of chemotherapy. You can go back to the old RT vs CMT papers of LeChevalier and Dillman to see some idea of what thoracic RT alone does to counts. Remember that this was old school thoracic inlet to 5 cm below the carina, with almost all the circulating blood pool irradiated thru the SVC and aorta, so worst case for us and it's about 5% rate of grade 3 cytopenias. There's no given response curve to know how long it lasts, but in my limited experience, it's a month at most. You're not blasting stem cells in the marrow (like chemo), it's just the circulating pool.
I've kept a moderately busy service this month so far. The infection rate in MN is still low, and we are aggressively screening as they enter the clinic. Stage 3 patients with NSCLC have a gun in their face and can't wait. There's no accepted regimen that shortens the course (thanks to @Puneeth Iyengar on twitter for sharing his reservations with 60/15 and chemo based on their exp ahead of pub. 10k <3 to him). For stage 1, I'm considering 54/3 and 50/5 if solid and growing and trying to triage the GGO's that I've surveilled for months. That's how I'm thinking of it 3/24/20 at 8 am CST. :)
Aside: We are very fortunate to be physicians. We have work, and we are needed. Friends around me are facing layoffs, etc. I feel very blessed to be in this role, at this time. The work units you interface with (therapy, dosimetry, etc) will all take their queues from you. Project calm and resolve. Channel Dr. Fauci. We are worried on the inside but the troops will benefit from your calm and ability to plan. Stay safe and beam on (when appropriate).
The available literature which has documented ALC levels at baseline and every month from the start of radiation up to one year (not reported beyond that because CBC with diff is simply not done out that long since there is no reason to) has the nadir at the end of RT or chemoRT that is sustained on the average of about a 50% recovery even out to one year. So far the type of chemo certainly matters (MMC, Cytoxan which are lymphodepleting) but not the case for most chemo, even with high systemic doses of chemo that's used with concurrent radiation the lymphocytes don't change. It is mostly a radiation effect.
This data is the same whether you look at data from GBM or rectal/anal cancer (head to toe), you radiate, the same results. The body does not respond with a compensatory release of IL2, IL7, IL15, lymphokines growth factors that are important for restoring lymphocyte levels, when localized radiation is used. The response is seen with a single 2 Gy or 4 Gy TBI, but not 6 weeks of radiation. The compensation doesn't happen with localized radiation. Maybe marrow has something to do with it for long term recovery, but the acute and subacute depletion is purely circulating cells. You get immediate depleting even after one day of radiation, and after 1 week, almost 50% of circulating lymphocytes are already gone. It is the integral dose to the circulating blood, and body locations where the greatest depletion occurs have also the greatest susceptibility to high grade lymphopenia.
@Puneeth Iyengar, can you share your observations with the 60/15 and chemo strategy?
Both large and even quite small XRT fields, and volumetric arcs as well, produce reduction in peripheral lymphocyte count. We all learned that radiotherapy “immunosuppressive.” Without definitive evidence, we assume these two observations are related. Are they? I don’t know. At the time of COVID-19, prudence, and that balances risk, determines whether to treat or wait. Nodal masses compressing airways or vessels should be treated. Reports of masses on CT or PET reports without immediate clinical symptoms might wait until symptoms arise. Lymphopenia can endure for a year, so waiting for a normal count may not be prudent.
Related Questions
While the actual infection of COVID-19 has more to do with hygiene, social distancing, and prevention such as drugs or vaccines, the susceptibility for the patient to develop symptomatic progression of COVID-19, once infected, has a strong theoretical possibility. The factors that impact severe lymphopenia after radiation therapy include field and fraction size, among other things such as baseline ALC (which is usually already low for the elderly, and those with poor KPS). In a locally advanced NSCLC/SCLC patient receiving prolonged courses of radiotherapy (>=30 fractions or >=6 weeks depending whether you do BID or QD), the rate of grade 3+ lymphopenia is extremely high (>50%), the lymphopenia is usually prolonged and doesn't fully recover for most patients even more than a year out of treatment. Therefore a hypofractionated approach (15 fractions or less) and non-elective nodal radiation should be taken as much as possible to reduce the chance for the patient to develop high grade lymphopenia, and hopefully make the patient less vulnerable to develop symptomatic progression of COVID-19, should they acquire it after completing treatment.