Is the Abscopal effect a "unicorn" and not worth chasing?

[Gfunk6]

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Editorial published in JCO: https://ascopubs.org/doi/full/10.1200/JCO.20.02046?af=R&

In conclusion, the study by McBride et al1 provides the clearest evidence so far that the abscopal effect, contrary to widely held perception in the field, remains exceedingly rare and is not clinically relevant when using anti–PD-1/PD-L1 therapies and SBRT for HNC (at least when applied to a single lesion).

 

[scarbrtj]

Unicorns don't exist. Abscopal effects do. However, when an abscopal event happens it's like "firing a 15-inch shell at a piece of tissue paper and it coming back and hitting you." When very rare and otherwise inexplicable things happen, if you understand the mechanism for the event you can explain why the event happened and reproduce it. IMHO we have abscopal events in clinic as often as Rutherford's alpha particle scatterings. But until we at least have some mechanism for abscopal events we can't hope to explain them or make them more common. My take!

 

[Haybrant]

Unicorns don't exist. Abscopal effects do. However, when an abscopal event happens it's like "firing a 15-inch shell at a piece of tissue paper and it coming back and hitting you." When very rare and otherwise inexplicable things happen, if you understand the mechanism for the event you can explain why the event happened and reproduce it. IMHO we have abscopal events in clinic as often as Rutherford's alpha particle scatterings. But until we at least have some mechanism for abscopal events we can't hope to explain them or make them more common. My take!

This is a great take. I think running these small studies is creating more hopium than is necessary And focus should be on more preclin studies, it’s just not ready for primetime, aside from maybe melanoma. In tumor boards it should be presented as Scar has so as not to feed into false hopes

 

[RickyScott]

Don’t you have to give medstudent some false hopes? Part of the roadmap.

 

[StIGMA]

Editorial published in JCO: https://ascopubs.org/doi/full/10.1200/JCO.20.02046?af=R&

there will be diseases where this is seen more frequently than others (and therefore be easier to study/optimize). H&N is a more challenging one

 

[evilbooyaa]

Agree with the guy on twitter who said chasing the abscopal effect yeti has put our field behind the 8-ball for at least a decade in the development of trials for oligometastatic disease.

That being said, the case reports for abscopal effect is NOT the way this trial was designed.

Abscopal effect case reports showed that RT works to RE-sensitize tumors that have become resistant to IT when patients develop clinical progression on IT. I have not seen any clinical evidence or case reports that actually suggest that SBRTing at initiation of IT does a damn thing, and the McBride paper confirms this (at least in H&N)

The OG (to me at least) Melanoma Case Report - https://www.nejm.org/doi/full/10.1056/NEJMoa1112824

Over the course of 2010, there was slight radiographic evidence of worsening disease, but treatment was continued with maintenance ipilimumab, since the patient was clinically well. Mild, asymptomatic hypothyroidism developed that required thyroid hormone supplementation, but she had no other clinically significant treatment-related toxicity. By November 2010, however, she had progressive enlargement of the pleural-based paraspinal mass and new splenic lesions (Figure 1B). To treat right-sided back pain caused by the paraspinal mass, palliative radiotherapy was initiated. In December 2010, a total of 2850 cGy was administered in three fractions over a period of 7 days to the paraspinal mass with 6-MV photons by means of a coplanar six-field intensity-modulated, image-guided technique (Figure 1F). This regimen is within the range of acceptable, commonly used dose-fractionation schemes.

One month after radiotherapy, in January 2011, a CT scan had not yet shown a response at the primary irradiated site, the right hilar lymph node, and the spleen (Figure 1C). The patient was given one additional dose of ipilimumab in February 2011. By April 2011, her targeted paraspinal lesion had regressed significantly (Figure 1D). Remarkably, lesions in areas not targeted by radiotherapy had also regressed (right hilar lymphadenopathy and splenic lesions [Figure 1D]). A subsequent CT scan obtained in October 2011 (10 months after radiotherapy) showed stability, with the continued presence of minimal disease (Figure 1E).

The only published case report of abscopal effect in H&N showed the same thing - Induction of the Abscopal Effect with Immunotherapy and Palliative Radiation in Metastatic Head and Neck Squamous Cell Carcinoma: A Case Report and Review of the Literature

He was initially enrolled on a clinical trial comparing first-line EXTREME chemotherapy versus ipilimumab and nivolumab, and was randomized to combination ipilimumab and nivolumab delivered concurrently every three weeks for four cycles. Follow-up imaging at eight weeks showed progression of disease, with growth of the primary and neck masses ulcerating through his skin (Figure 1A), as well as disease progression in the chest, with growth of previous nodules and development of additional pulmonary nodules, the largest measuring 2.4 cm (previously 1.6 cm, Figure 1B).


The patient had worsening symptoms associated with mass effect in the neck and was re-evaluated by Radiation Oncology at the request of the treating oncologist. He was treated with ‘QUAD SHOT’ for palliation [8], delivering 3.7 Gy BID x 2 days (total dose 14.8 Gy) to gross disease, and 3.3 Gy BID x 2 days (13.2 Gy) to microscopic areas at high risk for disease, including one nodal echelon beyond gross disease on the left (levels IB-V), and contralateral levels II-IV. No radiation was delivered to his lung disease. The patient continued through the third and fourth cycles of nivolumab and ipilimumab without breaks or delays. Radiation was delivered during the three-week time frame between immunotherapy cycles, and he tolerated treatment well with minimal pain and noticeable improvement in the left neck mass.

On follow-up CT scan at two weeks after completion of radiation, the primary and bulky left neck adenopathy had decreased in size by approximately 25% (Figure 1C). The metastatic pulmonary nodules had also all decreased in size with the largest nodule decreasing from 2.4 to 1.3 cm, approximately 50% (Figure (Figure1D).1D). His QUAD-SHOT regimen was repeated one month after initial treatment, as described above. Repeat imaging showed continued decrease in size of all neck and most lung disease, with one lung nodule minimally increasing in size. The patient received a third round of QUAD-SHOT as described above, with near complete resolution of his left neck mass. At 16 weeks from first round of radiation treatment, the patient had a continued response in his pulmonary metastases, followed by disease stability. At 20 weeks from start of radiation, one of his lung lesions had increased in size while the remaining lesions were either stable or decreased in size. At the time of this writing (10 months from initial diagnosis), he has completed a total of 14 cycles of ipilimumab and nivolumab on trial and is currently living with stable, asymptomatic disease.

 

[kimplera]

Agree with the guy on twitter who said chasing the abscopal effect yeti has put our field behind the 8-ball for at least a decade in the development of trials for oligometastatic disease.

who was that smart guy/gal?