Patients with advanced lung cancer can experience burdensome symptoms at the end of life. Pulmonologists can alleviate some of this suffering, but it’s a balancing act between doing too much and not enough, according to specialists who spoke at CHEST 2019, the annual meeting of the American College of Chest Physicians, during the session, “Don’t Stop Treating Me! Advanced Stage Lung Cancer, Beyond Palliation.”
“We as physicians often think our treatments will be the Holy Grail, but we need to appreciate what we can and cannot do, understanding that our efforts won’t help everyone,” said Russell Hales, MD, Director of the Thoracic Oncology Multidisciplinary Program at Johns Hopkins Medicine in Baltimore.
As a radiation oncologist, Dr. Hales is often asked by medical oncologists to treat advanced lung cancer aggressively, but this is not always the best course for an individual patient. With the “tremendous migration toward good outcomes” today—median survival is nearing 2 years with immunotherapy—comes the need for better palliative therapies, he said. “The value in radiation therapy may be seen most directly in the palliative setting.”
Dr. Hales outlined his approach to palliative radiation, and Jessica S. Wang Memoli, MD, Director of Bronchoscopy and Interventional Pulmonary at Medstar Washington Hospital Center in Washington, DC, discussed airway management.
Radiation to Palliate Symptoms
Palliative radiotherapy is indicated for malignant airway obstruction, hemoptysis, vascular compression, coughing, and pain—though few studies have formally studied its benefit. In one study that quantified its advantages, 237 patients received rigid bronchoscopy/external-beam radiotherapy, stents, or both for malignant airway obstruction.1 The combined modalities yielded a survival advantage: a median of 157 days vs 113 days for stents and 84 days for radiation therapy. “The take-home message is that radiation is an effective palliative therapy in these patients,” said Dr. Hales, who coauthored the study.
Indeed, the body of data showing a survival advantage for timely palliative care in non–small cell lung cancer (NSCLC) is growing. In a 2019 study of 23,154 patients with advanced NSCLC, among the 57% who received palliative care, its initiation between 31 and 365 days from diagnosis was associated with a 53% reduction in mortality compared to no palliative care.2
Although this study and others have helped to establish the value of a dedicated palliative care team, implementation remains spotty. Surveys have found that virtually all physicians see a benefit for palliative radiotherapy in NSCLC, yet few refer patients—in one study, only 1% did so.3
Dr. Hales believes the underlying reason is economic: “Our current pay structure requires the surrender of coverage for chemotherapy and radiation for patients enrolled in hospice. The median daily reimbursement for hospice care is about $150, whereas a course of palliative radiation can run $10,000,” he said. “This is a fundamental paradox. We have a real opportunity to help people, yet only 1% of patients get palliative radiotherapy.”
Approach to Radiotherapy in Stage III/IV Disease
Stage III NSCLC presents more of a dilemma, he continued, the question being the degree of benefit gained with concurrent chemoradiotherapy vs chemotherapy alone in incurable disease. In Dr. Hales’ experience, oncologists often request “radical” treatment based on the “opportunity for cure,” but only 20% of patients with stage III disease can be cured. Nevertheless, he said, oncologists frequently “go for it.”
Often a good option is a moderate approach, as shown in a study of 191 patients with incurable stage III NSCLC who were randomly assigned to concurrent chemotherapy and radiation (42 Gy in 15 fractions) or chemotherapy alone.4 Chemoradiation did impart a benefit, with a median time to disease progression of 7.0 months vs 4.2 with chemotherapy alone (P < .001); the median overall survival was 12.6 vs 9.7 months, respectively (P < .001).
“This was not a ‘definitive’ course of radiation, but the dose was slightly higher than the palliative doses we give,” he noted. “In patients with a poor performance status or poor-outcome disease, it’s an alternative to chemotherapy alone and an alternative to aggressive chemoradiation. Something ‘in between’ can be effective and have a fairly low symptom burden.”
In contrast to stage III disease, an aggressive course of thoracic radiation is clearly not indicated for stage IV disease, according to the American Society of Thoracic Oncology Evidence-Based Guidelines. “Aggressive” is defined as concurrent chemotherapy plus radiation or definitive radiation given for more than 3 weeks (ie, ≥ 15 fractions).
“But despite clear evidence showing no benefit in this population, there continues to be overuse of definitive radiation,” he observed. In a 2015 study, 49% of patients with stage IV disease received > 15 fractions of radiation and 19% received concurrent chemotherapy and radiation.5
This is a situation in which “too much of a good thing is not good at all,” Dr. Hales commented. Although a short course of radiation can sometimes be beneficial, one must be cautious and ensure the therapy is appropriate.
In summary, for incurable stage III NSCLC, concurrent chemoradiotherapy is reasonable and well tolerated; Dr. Hales gives it as 15 fractions. For stage IV NSCLC, concurrent chemoradiotherapy should not be offered, nor should protracted radiation regimens (> 10 fractions), he added, although 10 fractions are better than 1 to 5 for total symptom improvement and acute dysphagia and may have some survival benefit. “The appropriate regimen in stage IV disease is context- and patient-specific,” he added.
In patients with small cell lung cancer (SCLC), Dr. Hales uses prophylactic radiation for extensive disease. Some 75% of patients with SCLC have persistent intrathoracic disease after chemotherapy, and 90% have intrathoracic disease progression within 12 months. Palliative-dosed irradiation (30 Gy in 10 fractions) delivered to the initial areas of chest disease before recurrence can improve survival,6 but this approach has not been tested in NSCLC.
Management of Airway Obstruction
Dyspnea is a chief complaint of patients with terminal NSCLC. Dr. Wang Memoli described how proper management of central airway obstruction, maintenance of airway patency, and treatment of pleural effusions can significantly improve this symptom, often boost performance status, and potentially allow for more effective local antitumor treatment.
For tumor debulking, pulmonologists have multiple tools at their disposal: rigid bronchoscopy, laser, thermocoagulation/electrocautery, cryotherapy, endobronchial brachytherapy, photodynamic therapy, intratumoral chemotherapy/transbronchial needle injection, and a new transbronchial microinfusion device that works via balloon dilation. Each has its advantages and disadvantages (including some fairly high complication rates), but they can all help ameliorate airway obstruction. Once the airway is opened, stents can maintain patency.
The question has been whether these interventions really have a functional effect on patients. They do, according to a recent prospective outcome assessment among 65 patients treated mostly with mechanical debulking and airway stenting.7 The study concluded that therapeutic bronchoscopic interventions provide rapid and sustained improvements in symptoms, respiratory status, exercise capacity, and quality of life in malignant central airway obstruction and have a good safety profile.
For malignant pleural effusions, management includes long-term pleural drainage catheters, talc pleurodesis, repeat thoracentesis, and surgical pleurodesis. According to a systemic review, indwelling pleural catheters result in shorter hospital length of stay and fewer repeat pleural procedures than pleurodesis, but they carry a higher risk of cellulitis.8 The choice between these two approaches, Dr. Wang Memoli said, ultimately depends on the patient’s preferences.
The European Respiratory Society and European Association for Cardiac-Thoracic Surgery has issued the following statement on the management of malignant pleural effusions:
The main point, Dr. Wang Memoli emphasized, is that something can and should be done to palliate patients with pleural effusions. A recent systemic review of patients undergoing talc slurry pleurodesis, thoracoscopic talc poudrage, and indwelling pleural catheter placement concluded that all these treatments improve health-related quality of life.9 “The way it’s managed makes no difference in how patients felt long-term, though some interventions had a quicker effect. We just need to take care of this problem,” she said.
Dr. Wang Memoli encouraged pulmonologists at the meeting to “be less afraid of being aggressive to open the airway” and to engage patients in these discussions. “Find out what they are comfortable with. Helping patients feel better could ultimately affect their survival.” ■
DISCLOSURE: Dr. Hales has received a research grant from Genentech. Dr. Wang Memoli reported no conflicts of interest.
1. Mallow C, Thiboutot J, Semaan R, et al: External beam radiation therapy combined with airway stenting leads to better survival in patients with malignant airway obstruction. Respirology. March 12, 2018 (early release online).
2. Sullivan DR, Chan B, Lapidus JA, et al: Association of early palliative care use with survival and place of death among patients with advanced lung cancer receiving care in the Veterans Health Administration. JAMA Oncol. September 19, 2019 (early release online).
3. Lutz S, Spence C, Chow E, et al: Survey on use of palliative radiotherapy in hospice care. J Clin Oncol 22:3581-3586, 2004.
4. Strøm HH, Bremnes RM, Sundstrøm SH, et al: Concurrent palliative chemoradiation leads to survival and quality of life benefits in poor prognosis stage III non-small-cell lung cancer: A randomised trial by the Norwegian Lung Cancer Study Group. Br J Cancer 109:1467-1475, 2013.
5. Koshy M, Malik R, Mahmoo U, et al: Prevalence and predictors of inappropriate delivery of palliative thoracic radiotherapy for metastatic lung cancer. J Natl Cancer Inst 107:djv278, 2015.
6. Slotman BJ, van Tinteren H, Praag JO, et al: Use of thoracic radiotherapy for extensive stage small-cell lung cancer: A phase 3 randomised controlled trial. Lancet 385:36-42, 2015.
7. Mohan A, Shrestha P, Madan K, et al: A prospective outcome assessment after bronchoscopic interventions for malignant central airway obstruction. J Bronchology Interv Pulmonol. September 26, 2019 (early release online).
8. Iyer NP, Reddy CB, Wahidi MM, et al: Indwelling pleural catheter versus pleurodesis for malignant pleural effusions: A systematic review and meta-analysis. Ann Am Thorac Soc 16:124-131, 2019.