Hedy L. Kindler, MD
Raffit Hassan, MD
As reported by Hedy L. Kindler, MD, of the University of Chicago, and colleagues in the Journal of Clinical Oncology, ASCO has released a clinical practice guideline on the treatment of malignant pleural mesothelioma.1 The guideline was based on a systematic literature search and expert panel review of 222 relevant studies published between 1990 and 2017. The panel was co-chaired by Dr. Kindler and Raffit Hassan, MD, of the National Cancer Institute.
The guideline provides detailed evidence-based recommendations on diagnosis, staging, and treatment of malignant pleural mesothelioma. Recommendations on chemotherapy, cytoreductive surgery, and radiation therapy are reproduced/summarized here.
Chemotherapy
1.1: Chemotherapy should be offered to patients with mesothelioma because it improves survival and quality of life.
1.2: In asymptomatic patients with epithelial histology and minimal pleural disease who are not surgical candidates, a trial of close observation may be offered prior to the initiation of chemotherapy.
1.3: Selected patients with a poor performance status (2) may be offered single-agent chemotherapy or palliative care alone. Patients with a poor performance status of 3 or greater should receive palliative care.
2.1: The recommended first-line chemotherapy for patients with mesothelioma is pemetrexed (Alimta) plus platinum. However, patients should also be offered the option of enrolling in a clinical trial.
3.1: The addition of bevacizumab (Avastin) to pemetrexed-based chemotherapy improves survival in select patients and therefore may be offered to patients with no contraindications to bevacizumab. A randomized clinical trial demonstrating a benefit with bevacizumab used cisplatin/pemetrexed; data with carboplatin/pemetrexed plus bevacizumab are insufficient for a clear recommendation.
3.2: Bevacizumab is not recommended for patients with a poor performance status (2), substantial cardiovascular comorbidity, uncontrolled hypertension, age > 75, bleeding or clotting risk, or other contraindications to bevacizumab.
4.0: In patients who may not be able to tolerate cisplatin, carboplatin may be offered as a substitute for cisplatin.
5.1: Retreatment with pemetrexed-based chemotherapy may be offered in patients with pleural mesothelioma who achieved durable (> 6 months) disease control with first-line pemetrexed-based chemotherapy.
5.2: Given the limited activity of second-line chemotherapy in patients with mesothelioma, participation in clinical trials is recommended.
5.3: In patients for whom clinical trials are not an option, vinorelbine may be offered as second-line therapy.
6.1: In asymptomatic patients with epithelial mesothelioma and a low disease burden who are not surgical candidates, a trial of expectant observation may be offered before initiation of systemic therapy.
6.2: Front-line pemetrexed-based chemotherapy should be given for four to six cycles. For patients with stable or responding disease, a break from chemotherapy is recommended at that point.
6.3: There is insufficient evidence to support the use of pemetrexed maintenance in patients with mesothelioma, and thus it is not recommended.
In selected patients with early-stage disease, it is strongly recommended that maximal surgical cytoreduction be performed.— HEDY L. KINDLER, MD; RAFFIT HASSAN, MD; AND COLLEAGUES
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Surgical Cytoreduction
1.1: In selected patientswith early-stage disease, it is strongly recommended that maximal surgical cytoreduction be performed.
1.2: Maximal surgical cytoreduction as a single-modality treatment is generally insufficient; additional antineoplastic treatment (chemotherapy and/or radiation therapy) should be administered. This treatment decision should be made with multidisciplinary input involving thoracic surgeons, pulmonologists, and medical and radiation oncologists.
1.3: Patients with transdiaphragmatic disease, multifocal chest wall invasion, or histologically confirmed contralateral mediastinal or supraclavicular lymph node involvement should undergo neoadjuvant treatment before consideration of maximal surgical cytoreduction. Contralateral (N3) or supraclavicular (N3) disease should be a contraindication to maximal surgical cytoreduction.
2.1: Patients with histologically confirmed sarcomatoid mesothelioma should not be offered maximal surgical cytoreduction.
2.2: Patients with ipsilateral histologically confirmed mediastinal lymph node involvement should undergo maximal surgical cytoreduction only in the context of multimodality therapy (neoadjuvant or adjuvant chemotherapy). Optimally, these patients should be enrolled in clinical trials.
3.0: Maximal surgical cytoreduction involves either extrapleural pneumonectomy or lung-sparing options (pleurectomy/decortication, extended pleurectomy/decortication). When maximal surgical cytoreduction is offered, lung-sparing options should be the first choice, due to decreased operative and long-term risks. Extrapleural pneumonectomy may be offered in highly selected patients when performed in centers of excellence.
4.1.1: Maximal cytoreduction (either lung-sparing or non–lung-sparing) should be considered only in patients who meet specific preoperative cardiopulmonary functional criteria, have no evidence of extrathoracic disease, and are able to receive multimodality treatment (adjuvant or neoadjuvant).
4.1.2: In patients who have symptomatic pleural effusion, who have a poor performance status (2 or greater), or in whom maximal cytoreduction cannot be performed (due to disease extent or comorbid conditions), palliative approaches such as a tunneled permanent catheter placement or thoracoscopic exploration with partial resection and/or pleurodesis should be offered. In the latter case, additional biopsy to confirm the pathologic diagnosis should be performed during the procedure. If the patient is being evaluated for investigational therapy, material for additional studies (eg, molecular and/or immunologic profiling) should be obtained.
4.2: In patients who have symptomatic pericardial effusion, percutaneous catheter drainage or pericardial window may be performed.
5.1: Since surgical cytoreduction is not expected to yield an R0 resection, it is strongly recommended that multimodality therapy with chemotherapy and/or radiation therapy be administered.
5.2: Chemotherapy may be given pre- or postoperatively in the context of multimodality treatment.
5.3: Adjuvant radiation therapy may be associated with a decreased risk of local recurrence and may be offered to patients who have undergone maximal cytoreduction. Treatment is complex, and it should be delivered at experienced centers of excellence.
5.4: In the context of multimodality treatment, four to six cycles of pemetrexed/platinum-based chemotherapy may be administered pre- or postoperatively.
6.0: Intracavitary therapies (chemotherapy or photodynamic therapy) may be administered safely in experienced centers of excellence, preferably in the context of a clinical trial. Their role in improving outcome is indeterminate.
7.1: Tunneled pleural catheters are not recommended in patients who are candidates for maximal surgical cytoreduction, because of the risk of tumor implantation into the chest wall.
7.2: In patients who are not candidates for maximal surgical cytoreduction, tunneled pleural catheters or pleurodesis (performed via chest tube or thoracoscopy) may be offered. As noted previously, these procedures should be performed using the minimal number and size of incisions. Multidisciplinary input, including surgical consultation with a center of excellence, should be sought to optimize the management of pleural effusion and for consideration of investigational intracavitary therapies.
Radiation Therapy
1.1: Prophylactic irradiation of intervention tracts should generally not be offered to patients to prevent tract recurrences.
1.2: Adjuvant radiation should be offered to patients who have resection of intervention tracts found to be histologically positive.
2.1: Radiation therapy should be offered as an effective treatment modality to palliate patients with symptomatic disease.
2.2: Standard dosing regimens used in other diseases should be offered to patients with mesothelioma (8 Gyone fraction, 4 Gyfive fractions, or 3 Gy10 fractions).
3.0: Radiation therapy may be offered to patients with localized asymptomatic recurrence. The dosing fractionation is dependent on the site and extent of disease and should be determined by the radiation oncologist in consultation with the patient.
4.1: Hemithoracic adjuvant radiation therapy may be offered to patients who undergo non–lung-sparing cytoreductive surgery (extrapleural pneumonectomy), preferably in centers of excellence with experience in this modality for mesothelioma.
4.2: Hemithoracic neoadjuvant radiation therapy may be offered to patients who undergo non–lung-sparing cytoreductive surgery. This potentially toxic regimen remains experimental and should be performed only in highly experienced centers within the context of a clinical trial.
5.1: Hemithoracic adjuvant intensity-modulated radiation therapy may be offered to patients who undergo lung-sparing cytoreductive surgery (pleurectomy/decortication or extrapleural pneumonectomy). This potentially toxic regimen should be performed only in highly experienced centers, preferably in the context of a clinical trial.
5.2: Due to the potential for severe pulmonary toxicity, neoadjuvant radiation therapy is not recommended for patients who undergo lung-sparing surgical cytoreductive surgery.
6.1: For palliative radiation therapy, electrons, two-dimensional, three-dimensional, and intensity-modulated radiation therapy may be considered appropriate techniques, depending on the location of the treatment target and organs at risk.
6.2: For adjuvant or neoadjuvant hemithoracic radiation therapy, three-dimensional or intensity-modulated radiation therapy may be offered, respecting guidelines of organs at risk. Proton therapy may be considered in centers with significant experience, preferably in the context of a clinical trial.
7.0: Standard dosimetric guidelines for organs at risk should be used as established predictors of radiation toxicity.
Additional information is available at www.asco.org/thoraciccancer-guidelines and www.asco.org/guidelineswiki.
DISCLOSURE: For full disclosures of the study authors, visit www.jco.ascopubs.org.
REFERENCE
1. Kindler HL, Ismaila N, Armato SG 3rd, et al: Treatment of malignant pleural mesothelioma: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 36:1343-1373, 2018.
