We think [thoracic radiotherapy] should be offered now in addition to [prophylactic cranial irradiation] to all patients responding to initial chemotherapy.
—Berend J. Slotman, MD, PhD
Postoperative radiation therapy, given after adjuvant chemotherapy, significantly increased overall survival in non–small cell lung cancer (NSCLC) compared to chemotherapy alone, according to a study reported at ASCO’s 2014 Annual Meeting.1 That study, an analysis of records in the National Cancer Database, was one of nine lung cancer abstracts from ASCO singled out for their relevance to practicing radiation oncologists in a recent webinar.
“Modern [postoperative radiotherapy],” said Berend J. Slotman, MD, PhD, who discussed this and eight other studies at the webinar, “may increase overall survival by 5% compared to
adjuvant chemotherapy alone.”
The webinar, organized by the International Association for the Study of Lung Cancer (IASLC), also included radiation oncology highlights from the most recent World Conference on Lung Cancer (see page 34). The recorded webinar is available on the IASLC website.2
Two other phase III trials selected by Dr. Slotman, who is Chair of Radiation Oncology at VU University and Medical Center in Amsterdam, suggest that current chemoradiation therapies for stage III NSCLC are not improved by the addition of either surgery or consolidation chemotherapy. In one trial, surgery was compared to definitive concurrent chemoradiation in stage III NSCLC.3 In the other, patients with inoperable stage III NSCLC were randomly assigned to either concurrent chemoradiation or chemoradiation followed by consolidation chemotherapy with docetaxel and paclitaxel.4 In both trials, outcomes in the two arms were similar.
“So the choice between definitive chemoradiation and surgery should also be based on patient preference,” Dr. Slotman concluded. “And personally I would add experience of the center.”
Academic Center Outcomes
Two other studies he selected explain why institutional experience might affect choice.
In one, researchers used the National Cancer Data Base (jointly sponsored by the American College of Surgeons and the American Cancer Society) to compare outcomes in stage IIIA NSCLC in academic vs community cancer centers.5 They found that 30-day mortality was significantly lower at academic centers.
The other study looked at the association between an institution’s clinical trial enrollment numbers and outcome in one large trial (Radiation Therapy Oncology Group [RTOG] 0617), finding that median overall survival and progression-free survival were both significantly better in high-volume centers.6
Asked why outcomes would be better in academic centers, webinar speakers mentioned several potential reasons, including possibly better treatment care and facilities and the higher number of board-certified thoracic surgeons in academic centers.
Four other studies highlighted by Dr. Slotman related to brain metastases.
A phase III trial in NSCLC examined whether early stereotactic radiosurgery prior to systemic chemotherapy increased overall survival in patients with asymptomatic oligometastases to the brain compared to chemotherapy alone.7 No benefit was seen for stereotactic radiosurgery in this study’s selected patient group.
In another randomized trial, prophylactic cranial irradiation was compared to observation in resected stage IIIA N2 NSCLC patients at high risk of brain metastases following adjuvant chemotherapy.8 This trial was closed early due to slow accrual, but key results showed that prophylactic cranial irradiation increased disease-free, though not overall, survival and reduced the incidence of brain metastases.
Two small cell lung cancer (SCLC) trials also involved prophylactic cranial irradiation. Both were follow-ups of an earlier trial, which showed that prophylactic cranial irradiation reduced brain metastases and increased overall survival in patients with extensive SCLC, compared to observation alone. That trial was led by Dr. Slotman and published in The New England Journal of Medicine in 2007.9
In one of the follow-up trials, prophylactic cranial irradiation was again compared to observation in patients with extensive SCLC, but magnetic resonance imaging (MRI) was used to confirm the absence of brain metastases before trial entry.10 This trial was terminated because of futility; however, with a median follow-up of 9.4 months and 111 observed deaths, the median overall survival was higher in the observation arm—15.1 months compared to 10.1 months in the prophylactic cranial irradiation arm. Patients in the radiotherapy arm, despite their lower overall survival, had significantly fewer brain metastases.
“This is a very interesting study that requires further analysis to see whether use of MRI should change our policy in patients who will receive [prophylactic cranial irradiation],” Dr. Slotman observed.
Adding Thoracic Radiotherapy
The final highlighted trial of the webinar compared thoracic radiotherapy plus prophylactic cranial irradiation to prophylactic cranial irradiation alone, also in extensive SCLC.11 Led by Dr. Slotman, this study found that adding thoracic radiotherapy to prophylactic cranial irradiation increased overall and progression-free survival as well as intrathoracic control.
“We think [thoracic radiotherapy] should be offered now in addition to [prophylactic cranial irradiation] to all patients responding to initial chemotherapy,” Dr. Slotman concluded. ■
Disclosure: Dr. Slotman reported no potential conflicts of interest.
1. Robinson CG, Patel A, Bradley JD, et al: Postoperative radiotherapy (PORT) for pathologic N2 non-small cell lung cancer (NSCLC) treated with adjuvant chemotherapy: A review of the National Cancer Database. ASCO Annual Meeting. Abstract 7509. Presented June 1, 2014.
2. Updates on Radiation Oncology: WCLC 2013 AND ASCO 2014. July 18, 2014. Available at www.iaslc.org/webinars/updates-radiation-oncology-wclc-2013-and-asco-2014. Accessed August 25, 2014.
3. Eberhardt WE, Gauler TC, Pöttgen C, et al: Phase III study of surgery (S) versus definitive concurrent chemoradiotherapy boost (def ccCRTx-BOx) in patients (pts) with operable (OP+) stage IIIA(N2)/selected IIIb (sel IIIB) non-small cell lung cancer (NSCLC) following induction (IND) chemotherapy (CTx) and concurrent CRTx (ESPATUE). ASCO Annual Meeting. Abstract 7510. Presented June 1, 2014.
4. Park K, Ahn Y, Ahn J, et al: A multinational phase III randomized trial with or without consolidation chemotherapy using docetaxel and cisplatin after concurrent chemoradiation in inoperable stage III non-small cell lung cancer (CCheIN). ASCO Annual Meeting. Abstract 7500. Presented June 2, 2014.
5. Samson P, Patel A, Crabtree T, et al: Multidisciplinary treatment for stage IIIA non-small cell lung cancer (NSCLC): Does institution matter? ASCO Annual Meeting. Abstract 7512. Presented June 1, 2014.
6. Eaton BR, Pugh SL, Bradley JD, et al: The effect of institutional clinical trial enrollment volume on survival of patients with stage III non-small cell lung cancer treated with chemoradiation: A report of the Radiation Therapy Oncology Group (RTOG) 0617. ASCO Annual Meeting. Abstract 7551. Presented May 31, 2014.
7. Lim S, Lee J, Lee M, et al: Randomized phase III trial of stereotactic radiosurgery (SRS) versus observation for patients with asymptomatic cerebral oligo-metastases in non-small cell lung cancer (NSCLC). ASCO Annual Meeting. Abstract 8037. Presented June 2, 2014.
8. Wang S, Li N, Ou W, et al: A randomized trial of prophylactic cranial irradiation versus observation in patients with fully resected stage IIIA N2 non-small cell lung cancer and high risk of cerebral metastases after adjuvant chemotherapy. ASCO Annual Meeting. Abstract 7508. Presented June 1, 2014.
9. Slotman B, Faivre-Finn C, Kramer G, et al: Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med 357:664-672, 2014.
10. Seto T, Takahashi T, Yamanaka T, et al: Prophylactic cranial irradiation (PCI) has a detrimental effect on the overall survival (OS) of patients (pts) with extensive disease small cell lung cancer (ED-SCLC): Results of a Japanese randomized phase III trial. ASCO Annual Meeting. Abstract 7503. Presented June 2, 2014.
11. Slotman BJ, Faivre-Finn C, van Tinteren H, et al: Randomized trial on thoracic radiotherapy (TRT) in extensive-stage small cell lung cancer. ASCO Annual Meeting. Abstract 7502. Presented June 2, 2014.