Presurgery radiation shows benefit in lung cancer

Key clinical point: A new protocol that involves accelerated hemithoracic intensity modulated radiation before surgery for lung mesothelioma delivered encouraging results in patients with epithelioid tumors.

Major finding: Disease-free survival was 47 months in epithelial subtypes compared with 8 months in biphasic subtypes.

Data source: A single-center population of 62 patients with malignant pleural mesothelioma treated between November 2008 and October 2014.

Disclosures: The study authors had no relationships to disclose.

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Switching Up Mesothelioma Treatment

Implementing the treatment regimen for malignant pleural mesothelioma (MPM) that the Toronto researchers studied poses “several high stakes challenges,” Dr. Valerie Rusch and coauthors at Memorial Sloan-Kettering Cancer Center, New York, said in their invited commentary (J Thorac Cardiovasc Surg. doi: 10.1016/j.jtcvs.2015.10.038).

Dr. Valerie W. Rusch

But they noted challenges involved with conventional multi-modality treatment for MPM, namely the 6 months of intensive treatment. However, the experience of the Toronto researchers will be difficult to replicate, they said. “Such outstanding results reflect the expertise of Dr. de Perrot and colleagues in the surgical care of MPM and the excellence of their multidisciplinary program,” Dr. Rusch and coauthors said.

The study results are among the best reported for MPM to date, they added, but they asked why. “Are they solely related to patient selection or do they reflect the true impact of a novel approach to treatment?”

Patients selected for the treatment need to be able to undergo the extrapleural pneumonectomy (EPP) and the surgeon has to be able to predict the resectability of the tumor. But limitations in existing staging methods for MPM make it difficult to predict tumor resectability. “To avoid bronchial stump leaks and other serious complications after EPP requires experience along with meticulous surgical technique and postoperative care,” Dr. Rusch and colleagues said. “Only high-volume centers of excellence could potentially reproduce these results.”

Despite the waning in popularity of EPP, the study results underscore its effectiveness in carefully selected patients – “those with epithelioid tumor histology and no tumor metastases.” To corroborate the findings, reports on other centers’ experience along with human and animal studies rather than a randomized clinical trial are needed. “Dr. de Perrot and colleagues may have been not only bold but SMART,” Dr. Rusch and colleagues said.



The popularity of extrapleural pneumonectomy to treat asbestos-related thoracic mesothelioma has yielded to extended pleurectomy/decortication in recent years, but a recent study suggests that the extrapleural pneumonectomy procedure can achieve good results in a new protocol that involves administering radiation therapy before surgery as opposed the more conventional approach of radiation after surgery.

Researchers at the University of Toronto reported on their protocol that uses accelerated intensity modulated radiation therapy (IMRT) for malignant pleural mesothelioma (MPM) (J Thorac Cardiovasc Surg. doi: 10.1016/j.jtcvs.2015.09.129). They call the protocol SMART, for Surgery for Mesothelioma After Radiation Therapy.

“The rationale to develop this protocol was to optimize the delivery of radiation to the whole tumor bed, sterilize the edges of the tumor to limit the risk of spillage at the time of surgery, develop a shorter treatment plan and potentiate the activation of the immune system by using a hypofractionated regimen,” wrote Dr. Marc de Perrot and colleagues.

The protocol involves delivering 25 Gy of radiation in five daily fractions over a week to the entire side of the thorax with 5 Gy boosts based on imaging, followed by extrapleural pneumonectomy (EPP) 4-6 days later. Patients with three or more positive lymph notes (ypN2 disease) also are offered adjuvant chemotherapy.

The researchers performed the protocol on 62 patients from November 2008 to October 2014, which represents 24% of all patients with MPM seen at the institution in that period. Fifty-two patients were men and ages ranged from 41 to 75 years. Clinical stage of cancer ranged from T1N0 in 10 patients, to T2N0 in 35 and T3N0 in 13 (two had T4N0 and two had T3N2). Forty-five had right-side cancers. Six patients received an extended protocol for various reasons, including tumor extending to the chest wall.

All 62 patients completed IMRT and EPP. All but one had resection and reconstruction of the diaphragm, and all but four had resection and reconstruction of the pericardium.

Overall death rate was 4.8% (three patients). Results were better in patients with epithelioid tumors, with a median survival of 51 months and disease-free survival of 47 months. Those with biphasic subtypes had median survival of 10 months and disease-free survival of 8 months. Eight patients had ipsilateral chest recurrence. “This analysis demonstrates that the SMART approach is particularly encouraging for patients with epithelial subtype,” Dr. de Perrot and coauthors said. They no longer perform the SMART protocol on patients with biphasic subtype.

The protocol was not without complications. Twenty-four patients, about 38%, had serious complications that required intervention or worse. Twelve had atrial fibrillation, but none advanced to life-threatening disease. Among other complications, four had empyema – one resulting in death – and three had pulmonary emboli. One other patient in the complications group died from pneumonia, and another died from a heart attack at home.

This is the Toronto researchers’ second attempt at studying the three-modality approach. In their first attempt, only half the patients who started with preoperative chemotherapy went onto complete the radiation after surgery because of difficulties administering it (J Thorac Cardiovasc Surg. 2007;133:111-6; J Clin Oncol. 2009;27:1413-8). Also, about 25% of patients had disease progression during induction chemotherapy and could not go onto surgery.

They designed the most recent trial to deliver radiation before surgery because of the excellent local control of cancer along with evidence that MPM tumors were radio-sensitive. “Considering the risk of disease progression on induction chemotherapy, we felt that switching the order of therapy was potentially a better option for patients with surgically resectable disease,” Dr. de Perrott and colleagues said.

The researchers cited the study’s single-center nature with a single treatment arm, and the lack of longer-term follow-up, as limitations. “However, in our own experience, this approach has been very encouraging and has become our primary option for patients with surgically resectable MPM,” they noted.

The study authors had no conflicts to disclose.

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