Surgery for Mesothelioma After Radiation Therapy (SMART); A Single Institution Experience

Our plain-English summary of Surgery for Mesothelioma After Radiation Therapy (SMART); A Single Institution Experience, by W.G. Breen, Y.I. Garces, K.R. Olivier, et al (Frontiers in Oncology, 2020).

The study

• Authors: W.G. Breen, Y.I. Garces, K.R. Olivier, S.S. Park, K.W. Merrell, F.C. Nichols, T.D. Peikert, J.R. Molina, A.S. Mansfield, A.C. Roden, S.H. Blackmon, D.A. Wigle
• Journal: Frontiers in Oncology
• Published: 2020;10:392
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: The optimal treatment sequence for localized malignant pleural mesothelioma (MPM) is controversial. We aimed to assess outcomes and toxicities of treating localized MPM with neoadjuvant radiation therapy (RT) followed by extrapleural pneumonectomy (EPP). Methods: Patients were enrolled on an institutional protocol of surgery for mesothelioma after radiation therapy (SMART) between June 2016 and May 2017. Eligible patients were adults with MPM localized to the ipsilateral pleura. Patients underwent staging with PET/CT, pleuroscopy, bronchoscopy/EBUS, mediastinoscopy, and laparoscopy. Five fractions of RT were delivered using intensity modulated radiation therapy (IMRT), with 30 Gy delivered to gross disease and 25 Gy to the entire pleura. EPP was performed 4-10 days following completion of RT. Results: Five patients were treated on protocol. Median age was 62 years (range 36-66). Histology was epithelioid on initial biopsy in all patients, but one was found to have biphasic histology after surgery. Three patients had surgeon-assessed gross total resection, and two had gross residual disease. While all patients were clinically node negative by pretreatment staging, three had positive nodal disease at surgery. Patients were hospitalized for a median 24 days (range 5-69) following surgery. Two patients developed empyema, one of whom developed respiratory failure and subsequently renal failure requiring dialysis, while the other required multiple surgical debridements. Two patients developed atrial fibrillation with rapid ventricular response after surgery, one of whom developed acute respiratory distress requiring intubation and tracheostomy. At last follow-up, one patient died at 1.4 years after local and distant progression, two were alive with local and distant progression, and the remaining two were alive without evidence of disease at 0.1 and 2.7 years. Median time to progression was 9 months. Three patients received salvage chemotherapy. Conclusions: SMART provided promising oncologic outcomes at the cost of significant treatment related morbidity. Due to the significant treatment associated morbidity and favorable treatment alternatives, we have not broadly adopted SMART at our institution.

Copyright © 2020 Breen, Garces, Olivier, Park, Merrell, Nichols, Peikert, Molina, Mansfield, Roden, Blackmon and Wigle.

In plain English

Five patients with malignant pleural mesothelioma were treated at Mayo Clinic between June 2016 and May 2017 on a protocol called SMART (surgery for mesothelioma after radiation therapy). All were adults with localized disease, epithelioid on initial biopsy (one proved biphasic on surgical pathology), with no lymph node spread on pre-treatment staging. All were men; three were recorded as having asbestos exposure. Each received five daily radiation treatments to the affected chest (25 Gy to the whole pleura, 30 Gy to visible tumor). Four to 10 days later each had extrapleural pneumonectomy, an operation removing the lung with resection and reconstruction of the diaphragm and pericardium. At surgery, three had one positive lymph node each. All five had serious (grade 3 or higher) complications after surgery, four had infections, and median hospital stay was 24 days. No treatment-related deaths occurred within 90 days. One patient died 1.4 years after starting treatment; one remained disease-free at 2.7 years. The authors called the outcomes promising but the complications significant, and hesitated to adopt the approach widely. They noted the small group limited conclusions.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Single-institution report of patients treated on a prospective institutional treatment protocol (small case series, not randomized)
• Who was studied: Five adults with localized epithelioid malignant pleural mesothelioma judged to be surgical candidates, treated at Mayo Clinic, June 2016 to May 2017. Table 1 lists all five as male, with ages at diagnosis of 37 to 67. Three had left-sided and two had right-sided disease.
• Exposure: The study examined a treatment, not an asbestos exposure. Patients received radiation in five daily fractions over 1 week (25 Gy to the entire ipsilateral pleura, with a boost to 30 Gy to PET/CT-identified gross tumor) using IMRT. Extrapleural pneumonectomy followed 4 to 10 days later.
• Main results:
  • Table 1 records asbestos exposure as 'Yes' for 3 of the 5 patients (patients 2, 4 and 5) and 'No' for 2.
  • All five patients completed the pre-operative radiation. Side effects after radiation were limited: one patient had grade 2 dermatitis.
  • At surgery, 2 patients had no lymph node involvement (pN0) and 3 had lymph node involvement (pN1), despite all being node negative on pre-treatment staging. Each of the three pN1 patients had one positive node.
  • The surgeons assessed resection as R1 in 3 patients and R2 in 2 patients.
  • All five patients had epithelioid histology on initial biopsy. One patient was found to have biphasic histology on the surgical specimen (90% epithelioid component).
  • The median hospital stay after surgery was 24 days (range 5 to 69).
  • All five patients had grade 3 or higher (CTCAE) toxicity after surgery.
  • Four of the five patients developed significant infections after surgery requiring antibiotics. Two developed empyema.
  • There were no treatment-related deaths within 90 days of surgery.
  • One patient died of cardiopulmonary failure with progressive recurrent disease 1.4 years after starting treatment. The other four were alive at last follow-up.
  • One patient remained disease-free 2.7 years after treatment.
  • Median time to progression was 9 months. All three patients whose disease progressed had progression both inside and outside the chest.
  • Three patients received salvage chemotherapy with carboplatin and pemetrexed. One of them also received vinorelbine.
• The authors' conclusion: The authors concluded that SMART provided promising cancer outcomes at the cost of significant treatment-related complications. They said that, given these complications and the alternatives available, they have hesitated to adopt it broadly at their institution and instead routinely use pleurectomy/decortication followed by IMRT.
• Limitations the authors state:
  • The authors stated that the main limitations relate to the small size of the cohort.
  • The authors stated that, because so few patients were enrolled, no definitive conclusions about cancer outcomes can be drawn.
  • The authors stated that one of the five patients was lost to follow-up shortly after hospital discharge.
  • The authors stated that the study was not randomized, so it cannot compare SMART with pleurectomy/decortication plus IMRT.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Pleural Mesothelioma, Extrapleural Pneumonectomy (EPP), Ipsilateral pleura, Staging, Bronchoscopy, Mediastinoscopy, Pleura.

Related studies

• A feasibility study evaluating Surgery for Mesothelioma After Radiation Therapy: the "SMART" approach for resectable malignant pleural mesothelioma — B.C. Cho, R. Feld, et al. (2014)
• Repeat cytoreductive surgery and heated intraperitoneal chemotherapy may offer survival benefit for intraperitoneal mesothelioma: a single institution experience — J. Wong, A.L. Koch, et al. (2014)
• Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for disseminated intra-abdominal malignancies in children-a single-institution experience — O. Zmora, A. Hayes-Jordan, et al. (2018)
• Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin in pediatric patients with peritoneal mesothelioma: a single institution experience and long term follow up — P. Malekzadeh, M. Good, et al. (2021)
• Surgery for malignant pleural mesothelioma after radiotherapy (SMART): final results from a single-centre, phase 2 trial — B.C.J. Cho, L. Donahoe, et al. (2021)
• Metastatic carcinoma to the thyroid gland: a single institution 20-year experience and review of the literature — P.A. Moghaddam, K.M. Cornejo, et al. (2013)

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