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Study Results Support Use of Proton Therapy for Recurrent NSCLC

Samson, Kurt

doi: 10.1097/01.COT.0000516148.82183.37

SAN FRANCISCO—Patients with recurrent lung cancer may respond favorably to intensity-modulated proton therapy (IMPT), according to the largest study to date evaluating the relatively new radiation technique in patients who have historically been considered ineligible for curative treatment.

More than three-quarters of patients were free from local recurrence 1 year after IMPT and less than one in 10 patients had severe side effects. The findings were presented at the 2017 Multidisciplinary Thoracic Cancers Symposium.

For non-small cell lung cancer (NSCLC) patients who received higher IMPT doses, the 1-year progression-free survival (PFS) rate was five times higher than for others, said Jennifer Ho, MD, lead author of the study and a radiation oncology resident at the University of Texas MD Anderson Cancer Center, Houston.

“Treating patients who have already received a prior course of thoracic radiation is a common clinical scenario, and it is particularly challenging to subsequently provide strong enough radiation doses to eliminate the new tumor without causing significant harm to normal tissues,” she noted.

Proton therapy with IMPT technology is a form of technological precision therapy that uses highly sophisticated “pencil beam” scanning technology to precisely deliver proton beam to the target volume in a layer-by-layer manner. While it may not be able to limit damage to the normal tissues within the area of recurrent cancer, using precision delivery techniques, it can significantly limit radiation doses to the surrounding normal tissues.

For patients who received thoracic radiotherapy in the past, there are concerns about cumulative radiation exposure to organs near thoracic tumors such as the heart, lungs, and esophagus. Most patients whose lung cancer recurs are generally offered only palliative options.

“Reirradiation of thoracic malignancies is a treatment challenge, with concerns for toxicity and inability to deliver definitive doses,” said Ho. “Our study is the first to show that IMPT can be safe and effective for these patients—and that it offers these patients a chance for lasting cancer control without adding significant toxicity.”

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NSCLC Study Results

Ho and her colleague Joe Y. Chang, MD, senior author and Professor of Radiation Oncology at MD Anderson, conducted a retrospective study of records for 27 patients treated with IMPT in prospective clinical trials at MD Anderson, 22 of whom had NSCLC and all of whom were previously treated with thoracic radiation.

Each subject underwent 4D CT-based simulation, motion, and individualized tumor-motion dose-uncertainty analysis. They also underwent 4D CT resimulation during treatment. Each dose was recalculated to an equivalent dose in 2 Gy fractions (EQD2). In all, 93 percent of the patients had recurrence of thoracic cancer. In the remaining 7 percent, IMPT was delivered sequentially after a course of thoracic stereotactic ablative radiotherapy to a median dose of 66 EQD2 Gy, ranging from range 43.2 to 84 Gy.

Time to reirradiation ranged from 1 month to 212 months, with a median of 29.5 months, while median follow-up for all patients was 11.2 months.

In the 22 patients treated for NSCLC, the median time until re-irradiation was 29.5 months and median follow-up was 11.2 months or 25.9 months for those still alive. Median overall survival (OS) was 18 months, with a 1-year OS of 54 percent.

Four patients experienced in-field local failure (LF), but 78 percent had 1-year and 2-year freedom from LF. At 1 year, freedom from local-regional relapse (LRR), and PFS rates were 61 percent and 51 percent, respectively.

Patients who received 66 EQD2 Gy or higher had improved 1-year freedom from LF (100% vs. 49%), 1-year freedom from LRR (84% vs. 23%), and 1-year PFS (76% vs. 14%).

Worse OS was associated with higher original T stage at diagnosis, squamous histology, and higher recurrent tumor volume.

Reirradiation with IMPT was well-tolerated. Only two patients experienced moderate to severe long-term lung toxicity (i.e., grade 3 or higher side effects). There were no severe long-term esophageal side effects nor any life-threatening toxicities.

“Historically, repeat radiation at a higher, curative dose was not possible with older, less-precise radiation techniques because the cumulative radiation dose necessary to treat the cancer would cause too much toxicity,” said Ho. “In lung cancer, tumors are close to the esophagus, aorta, and spinal cord, and all of these critical structures are vital for the body to function. The proton beam—and pencil beam in particular—provides much more conformal radiation, which means higher doses to tumors and lower dosages to critical structures nearby.”

The results suggest that, compared to other radiation types, IMPT is the optimal treatment for retreatment of thoracic cancers.

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Clinical Implications

“This study provides a ray of hope for a select group of patients with recurrent lung cancers who might derive benefit from aggressive local therapy for their cancer. For these patients, proton therapy with IMPT may provide durable local control, which could extend survival,” commented Pranshu Mohindra, MD, Assistant Professor of Radiation Oncology at the University of Maryland School of Medicine in Baltimore.

“This study is important because it brings awareness about a novel treatment modality. IMPT combines unique physical characteristics of proton beam therapy with the technological advances in proton treatment delivery allowing delivery of protons using pencil beam scanning.”

He told Oncology Times that local control rates in the study are amongst the highest reported.

“One of the reasons why this was possible is because the study team was able to deliver full doses of radiation. In this patient population, where surgery is typically not feasible and chemotherapy response rates are limited, availability of this new treatment approach provides clinicians with an additional tool in their armamentarium to treat patients with cancer.”

Mohindra emphasized that not all patients are candidates for IMPT reirradiation, which is most suited for patients with relatively localized recurrences, especially in areas close to the central chest structures: spinal cord, esophagus, heart, and great vessels.

“From the public standpoint, it is important to be aware of this additional treatment option for select patients with recurrent thoracic cancers. They can discuss this with their radiation oncologists if reirradiation is feasible. There are many academic centers and even community practices that may have expertise with reirradiation. If feasible, it might be a good idea to actually visit a proton center.”

It is also important to note that reirradiation, whether with IMRT (photons) or IMPT (protons), may still have risks of serious toxicities, including death, Mohindra cautioned, so a detailed discussion of risks and benefits is needed. This is best done with a radiation oncologist with expertise in this area.

“There are some logistic hurdles to wide spread adoption of this approach in clinical practice, he continued.

“At this point, there are only a handful of centers across the country with this ability, however more centers are in development. Until then, clinicians are encouraged to refer patients to proton centers with IMPT ability.”

Another potential barrier is that insurance companies may not cover proton therapy, he said.

“Reports like Dr. Ho's study will help increase awareness of medical directors within the insurance companies who can then help update the policies. Most proton centers will work with patients and their insurances to advocate regarding an individual patient's proposed benefits with proton therapy.”

The results need to be duplicated at other institutions with IMPT capability and longer term outcomes data would be helpful to rule out any safety concerns, Mahindra noted, adding that future studies should also explore dosimetric implications of reirradiation to provide guidelines regarding safe doses.

Kurt Samson is a contributing writer.

Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
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