Proton Therapy Improves Outcomes in Recurrent Lung Cancer

Roxanne Nelson, BSN, RN

March 22, 2017

Intensity-modulated proton therapy (IMPT) may be the optimal choice for patients with lung cancer who experience recurrence and who could potentially benefit from re-irradiation.

In a new review of IMPT for reirradiation in lung cancer — which is the largest such review to date but included only 27 patients — most patients remained free from local and regional relapse at 1 year.

Importantly, the procedure was well tolerated, with only 2 patients (7%) reporting grade 3 or higher adverse events. None of the patients experienced severe long-term esophageal side effects or any life-threatening toxicities.

The study was presented at the 2017 Multidisciplinary Thoracic Cancers Symposium.

"Treating patients who have already received a prior course of thoracic radiation is a common clinical scenario," said lead author, Jennifer Ho, MD, a resident in radiation oncology at the University of Texas MD Anderson Cancer Center in Houston, at a press briefing.

"Local recurrences are a common problem in lung cancer and patients do not  have a lot of treatment options," she said. "Most of them aren't candidates for surgery, and offering a second course of radiation raises concerns about the cumulative dose causing damage to organs."

Historically, Dr Ho noted, about 20% to 30% of patients have experienced moderate, severe, or even fatal side effects after reirradiation. Because of the high rate of toxicities, most patients are typically not offered any additional radiation therapy or are offered just palliative radiation at low doses that can treat symptoms.

Proton therapy has been studied in a variety of cancer types and has been controversial largely because of its cost. For example, proton therapy in prostate cancer cost $24,400 more than standard conformal radiotherapy (P < .001) and $11,000 more than 35 daily fractions of intensity-modulated radiotherapy.

The effectiveness of proton therapy compared with conventional modalities is also uneven. Proton radiation decreases radiation dose and toxicity to normal tissue compared with traditional photon radiation. However, previous results of a randomized controlled trial comparing proton-beam therapy with conventional radiotherapy in lung cancer found that while it was as effective as the conventional modality, it wasn't less toxic.  

But Dr Ho explained that there are now two types of proton beam radiation: the older passive type and IMPT, which is newer and better at avoiding critical structures during treatment.

"IMPT can precisely target the tumor and spare nearby normal tissue, to safely deliver a higher, curative radiation dose," she said.

Improved Survival Outcomes

In this retrospective study, Dr Ho and colleagues reviewed the medical charts of 27 patients who had received reirradiation with IMPT for thoracic tumors, via prospective clinical trials at a single institution between 2011 and 2016.

Of this group, 22 (81%) had non-small cell lung cancer; every patient had previously received curative radiation therapy. IMPT was administered for disease recurrence (93%) or sequentially after a course of thoracic stereotactic ablative radiotherapy (7%), to a median dose of 66 EQD2 Gy (range, 43.2 to 84 Gy).

The median time to reirradiation was 29.5 months (range, 0.1 to 21.2 months).

The median follow-up was 11.2 months, and median overall survival was 18 months after initiation of IMPT reirradiation, with a 1-year overall survival of 54%.

At 1 year after retreatment, 4 patients (15%) experienced an in-field local failure, which extrapolated to 1-year and 2-year freedom from local failure rates of 78%. The 1-year freedom from local-regional relapse and 1-year progression-free survival rates was 61% and 51%, respectively.

Patients who were prescribed a higher dose of IMPT reirradiation were less likely to experience recurrence or progression, explained Dr Ho.

At 1-year follow-up, patients who received 66 EQD2 Gy or higher were twice as likely to be free from local failure (100% vs 49%; P = .01) and nearly four times as likely to be free from local-regional failure (84% vs 23%; P = .035).

The 1-year progression-free survival rate was also significantly higher (76% vs 14%; P  = .05).

Reirradiation was well tolerated, with only 2 patients experiencing late grade 3 pulmonary toxicity, and none with grade 3 or higher esophagitis, explained Dr Ho. Only 7% of patients experienced serious toxicity, a rate much lower than that in previous studies, which have reported rates up to  30%.

Protons Hold Promise

Commenting on the paper, moderator Pranshu Mohindra, MD, from the University of Maryland, Baltimore, reiterated that treatment options have been limited for these patients, and reirradiation with conventional options can be difficult.

"Protons have unique physical characteristics which make them an exciting option for treatment of tumors in critical locations as in thoracic cancers," said Dr Mohindra. "IMPT is an even more advanced form."

"In this study, 85% of patients receive a dose of 60 Gy or more, and 60 Gy is the same dose as what is used in primary treatment," he said. "To be able to receive such a high dose safely is impressive."

"Continued reporting of long-term outcomes with IMPT will guide future practices and research," Dr Mohindra added.

Dr Ho has disclosed no relevant financial relationship. Several coauthors report relationships with industry as noted in the abstract.

2017 Multidisciplinary Thoracic Cancers Symposium. Abstract 5. Presented March 16, 2017.

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