Page 25 - Read Online

Housman et al. J Cancer Metastasis Treat 2021;7:69 https://dx.doi.org/10.20517/2394-4722.2021.159 Page 9 of 12

[52]
A landmark study by Rimner et al. evaluated the safety of IMPRINT after neoadjuvant platinum-based
chemotherapy and P/D. They found that after a total of 27 underwent a protocol with a median dose of 46.8
Gy (range 28.8 to 50.4 Gy), only six patients experienced grade 2 radiation pneumonitis, and two patients
experienced grade 3. No patients had grade 4 or 5 toxicities, and all 8 patients recovered with
corticosteroids .
[52]
Unfortunately, it is unclear whether adjuvant radiation even provides appreciable local control. In a study
by Gupta et al. , 123 patients underwent P/D and received adjuvant external beam radiotherapy. An
[50]
additional 54 patients received brachytherapy for residual tumor. The 1-year local control rate was 42%,
with a median survival of 13.5 months . Overall survival was negatively affected by radiation dose < 40 Gy,
[50]
non-epithelioid histology, left-sided disease, and use of implants. The investigators concluded that residual
disease could not be eradicated with radiation with or without brachytherapy, and local control may require
further surgery. It should be noted that the study investigated patients treated from 1974 to 2003, which may
[50]
have included less sophisticated therapy than modern techniques .

The SAKK 17/04 study, a multicenter phase II trial, explored the utility of hemi-thoracic radiation after
[53]
neoadjuvant chemotherapy and EPP . A total of 54 patients were randomized into radiation and no
radiation. Median survival was 20 months in both groups. The authors concluded the while a sicker patient
population may be responsible for their outcomes, the use of radiation could not be supported. They did
appear to question the contribution of the surgery as they noted the “role of extrapleural pneumonectomy
[53]
has been called into question by the development of lung-sparing procedures with less morbidity” .

Minatel et al. report successful radiation therapy after P/D. Minatel et al. published a series of 20
[54]
[54]
patients with overall median survival of 33 months and progression-free survival of 29 months with a 2-year
survival rate of 70% and a 3-year survival rate of 49%. There was no reported fatal toxicity. Locoregional
control at 2 years was 68% and 3 years was 59%. The predominant pattern of failure was distant, and only 3
of the 20 patients developed isolated locoregional recurrence .
[54]

No therapy for MPM recurrence has been universally accepted, and the elements of multimodal treatment
continue to be studied, including radiation, IMPRINT, chemotherapy, immunotherapy, iodine,
photodynamic therapy, and hyperthermic intraoperative chemotherapy [19,22] .

ONGOING TRIALS
There are several notable ongoing trials evaluating multimodal therapy for MPM. Referenced earlier, the
MARS 2 study will evaluate outcomes of platinum-based chemotherapy plus P/D vs. chemotherapy
alone . EORTC 1205 is a randomized phase II trial that compares neo-adjuvant and adjuvant courses of
[43]
cisplatin and pemetrexed with a standardized protocol of P/D . NCT02707666 is a single-arm study at the
[14]
University of Chicago exploring pembrolizumab, P/D, and postoperative chemotherapy that is currently
recruiting. Another study, NCT02592551, out of Baylor St. Luke’s in Houston, seeks to investigate
durvalumab and durvalumab plus tremelimumab before surgical resection (EPP or P/D) which is no longer
recruiting. NCT04897022 Memorial Sloan Kettering in New York is one of many trials investigating the use
of immunotherapeutic agents with the use of IMPRINT. A trial out of John’s Hopkins, NCT03918252, is
investigating neoadjuvant immune checkpoint blockade with nivolumab in resectable MPM. Another
promising trial, NCT04158141, is a Phase III randomized trial of P/D plus chemotherapy with or without
Adjuvant IMPRINT.