Meeting NewsPerspective

Single-dose radiotherapy should be standard for metastatic spinal canal compression

CHICAGO — Patients with metastatic spinal canal compression who received a single radiation dose achieved ambulatory status and OS comparable to those who received a multifraction dose administered over 1 week, according to results of a prospective randomized phase 3 noninferiority trial presented at ASCO Annual Meeting.

“A single dose of radiotherapy, at least in our minds, is now recommended in this setting,” Peter Hoskin, MD, FCRP, FRCR, oncologist at Mount Vernon Cancer Centre in Middlesex, United Kingdom, said during a press conference. “This has enormous advantages for patients, many of whom have very short survival. Of course, it also is increasingly cost-effective.”

Up to 10% of all patients with cancer will develop metastatic spinal cord compression. The condition can put pressure on the spinal canal, causing back pain, tingling, numbness and difficulty walking.

Radiation therapy often is used to relieve pain, maintain or increase mobility, and improve neurological function. However, no standard radiation schedule exists. Treatment ranges from a single 8-Gy dose to 40 Gy administered in 20 fractions.

Hoskin and colleagues conducted the SCORAD III trial to determine whether single-dose radiotherapy demonstrated comparable efficacy to 20 Gy administered in five fractions without compromising outcomes.

The analysis included 688 patients (median age, 70 years; 73% men) treated at 47 centers in United Kingdom and Australia.

All patients had MRI– or CT scan–confirmed spinal cord or cauda eqina (C1-S2) compression treatable within a single radiation field. Patients had not undergone prior radiation therapy to the same area, and all had a life expectancy of at least 8 weeks.

Common tumors included prostate (44%), lung (18%), breast (11%) and gastrointestinal (11%).

Researchers randomly assigned patients to external beam spinal canal radiation therapy in a single 8-Gy dose (n = 345) or in a 20-Gy dose administered in five fractions over 5 days (n = 343). Baseline characteristics were comparable between groups.

Investigators stratified results by center, ambulatory status, primary tumor site, and presence or absence of nonskeletal metastases.

Ambulatory status at week 8 served as the primary endpoint. Researchers assessed patient status on a four-point scale: grade 1, full function; grade 2, ability to walk with a walking aid, such as a walker or cane; grade 3, difficulty walking, even with walking aids; grade 4, wheelchair dependent.

Most patients (66%) had ambulatory status 1 or 2 at study entry.

Researchers established a noninferiority margin of 11% for comparing the proportion of patients who had ambulatory status 1 or 2 at week 8.

A comparable percentage of evaluable patients assigned single-dose and multifraction radiation therapy either maintained or improved to ambulatory status 1 or 2 by week 8 (69.5% vs. 73.3%; risk difference, –3.78; 90% CI, –11.85 to 4.28).

Hoskin and colleagues reported no statistically significant differences between the single-fraction and multifraction groups with regard to rates of overall positive response (risk difference, –3.78; 95% CI, –11.85 to –4.28), overall negative response (risk difference, 3.78; 95% CI, –4.28 to 11.85), or percentage of patients whose ambulatory status changed from grade 1 or 2 before radiation therapy to grade 3 or grade 4 after radiation therapy (risk difference, 3.96%; 95% CI, –2.32 to 10.25).

Researchers reported median survival of 13 weeks in the entire cohort. Results revealed no significant difference in OS between the single-dose and multifraction groups (12.4 weeks vs. 13.7 weeks; HR = 1.02; 95% CI, 0.86-1.21).

Grade 3 and grade 4 adverse events occurred in similar percentages of patients in the single-dose and multifraction groups (20.6% vs. 20.4%); however, fewer patients assigned the single-dose schedule experienced grade 1 or grade 2 events (51% vs. 56.9%).

Underrepresentation of younger patients and patients with metastatic breast cancer may limit the findings, according to researchers. Surgery in addition to or instead of radiation therapy may be appropriate for certain patients, and there may be cases when short-course radiation is not ideal, investigators added.

“Our findings establish single-dose radiotherapy as the standard of care for metastatic spinal canal compression, at least for patients with a short life expectancy,” Hoskin said in a press release. “For patients, this means fewer hospital visits and more time with family. ...

“Longer radiation may be more effective for preventing regrowth of metastases in the spine than single-dose radiation,” he added. “Therefore, a longer course of radiation may still be better for patients with a longer life expectancy, but we need more research to confirm this.” – by Mark Leiser

Reference:

Hoskin P, et al. Abstract LBA10004. Presented at: ASCO Annual Meeting; June 2-6, 2017; Chicago.

Disclosure: Cancer Research UK funded the study. The researchers report research funding to their institutions from AstraZeneca and Varian Medical Systems; honoraria from and consultant/advisory roles with Amtene and Eisai; and travel, accommodations or expenses from Eisai and Teva.

CHICAGO — Patients with metastatic spinal canal compression who received a single radiation dose achieved ambulatory status and OS comparable to those who received a multifraction dose administered over 1 week, according to results of a prospective randomized phase 3 noninferiority trial presented at ASCO Annual Meeting.

“A single dose of radiotherapy, at least in our minds, is now recommended in this setting,” Peter Hoskin, MD, FCRP, FRCR, oncologist at Mount Vernon Cancer Centre in Middlesex, United Kingdom, said during a press conference. “This has enormous advantages for patients, many of whom have very short survival. Of course, it also is increasingly cost-effective.”

Up to 10% of all patients with cancer will develop metastatic spinal cord compression. The condition can put pressure on the spinal canal, causing back pain, tingling, numbness and difficulty walking.

Radiation therapy often is used to relieve pain, maintain or increase mobility, and improve neurological function. However, no standard radiation schedule exists. Treatment ranges from a single 8-Gy dose to 40 Gy administered in 20 fractions.

Hoskin and colleagues conducted the SCORAD III trial to determine whether single-dose radiotherapy demonstrated comparable efficacy to 20 Gy administered in five fractions without compromising outcomes.

The analysis included 688 patients (median age, 70 years; 73% men) treated at 47 centers in United Kingdom and Australia.

All patients had MRI– or CT scan–confirmed spinal cord or cauda eqina (C1-S2) compression treatable within a single radiation field. Patients had not undergone prior radiation therapy to the same area, and all had a life expectancy of at least 8 weeks.

Common tumors included prostate (44%), lung (18%), breast (11%) and gastrointestinal (11%).

Researchers randomly assigned patients to external beam spinal canal radiation therapy in a single 8-Gy dose (n = 345) or in a 20-Gy dose administered in five fractions over 5 days (n = 343). Baseline characteristics were comparable between groups.

Investigators stratified results by center, ambulatory status, primary tumor site, and presence or absence of nonskeletal metastases.

Ambulatory status at week 8 served as the primary endpoint. Researchers assessed patient status on a four-point scale: grade 1, full function; grade 2, ability to walk with a walking aid, such as a walker or cane; grade 3, difficulty walking, even with walking aids; grade 4, wheelchair dependent.

Most patients (66%) had ambulatory status 1 or 2 at study entry.

Researchers established a noninferiority margin of 11% for comparing the proportion of patients who had ambulatory status 1 or 2 at week 8.

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A comparable percentage of evaluable patients assigned single-dose and multifraction radiation therapy either maintained or improved to ambulatory status 1 or 2 by week 8 (69.5% vs. 73.3%; risk difference, –3.78; 90% CI, –11.85 to 4.28).

Hoskin and colleagues reported no statistically significant differences between the single-fraction and multifraction groups with regard to rates of overall positive response (risk difference, –3.78; 95% CI, –11.85 to –4.28), overall negative response (risk difference, 3.78; 95% CI, –4.28 to 11.85), or percentage of patients whose ambulatory status changed from grade 1 or 2 before radiation therapy to grade 3 or grade 4 after radiation therapy (risk difference, 3.96%; 95% CI, –2.32 to 10.25).

Researchers reported median survival of 13 weeks in the entire cohort. Results revealed no significant difference in OS between the single-dose and multifraction groups (12.4 weeks vs. 13.7 weeks; HR = 1.02; 95% CI, 0.86-1.21).

Grade 3 and grade 4 adverse events occurred in similar percentages of patients in the single-dose and multifraction groups (20.6% vs. 20.4%); however, fewer patients assigned the single-dose schedule experienced grade 1 or grade 2 events (51% vs. 56.9%).

Underrepresentation of younger patients and patients with metastatic breast cancer may limit the findings, according to researchers. Surgery in addition to or instead of radiation therapy may be appropriate for certain patients, and there may be cases when short-course radiation is not ideal, investigators added.

“Our findings establish single-dose radiotherapy as the standard of care for metastatic spinal canal compression, at least for patients with a short life expectancy,” Hoskin said in a press release. “For patients, this means fewer hospital visits and more time with family. ...

“Longer radiation may be more effective for preventing regrowth of metastases in the spine than single-dose radiation,” he added. “Therefore, a longer course of radiation may still be better for patients with a longer life expectancy, but we need more research to confirm this.” – by Mark Leiser

Reference:

Hoskin P, et al. Abstract LBA10004. Presented at: ASCO Annual Meeting; June 2-6, 2017; Chicago.

Disclosure: Cancer Research UK funded the study. The researchers report research funding to their institutions from AstraZeneca and Varian Medical Systems; honoraria from and consultant/advisory roles with Amtene and Eisai; and travel, accommodations or expenses from Eisai and Teva.

    Perspective
    Joshua Jones

    Joshua A. Jones

    • This really is an important study. The effects of spinal cord compression can truly be devastating for patients and their families. We have traditionally used longer courses of radiotherapy, which requires patients to come in each day over a week, 2 weeks, 3 weeks or 4 weeks. This is the first study that really shows equal outcomes in terms of meaningful benefit with a single dose of radiotherapy versus a much longer course, allowing patients to spend more time with their families and more time doing the things they want to do. We still have work to do to figure out the most appropriate regimen for patients who live longer than the average of 3 months. But for many patients, this is going to provide tremendous benefit, with the idea that sometimes less really is more.

      • Joshua A. Jones, MD, MA
      • ASCO expert
        Hospital of the University of Pennsylvania
    • Disclosures: Jones reports a relationship with American Society for Radiation Oncology.
    Perspective
    Sue Yom

    Sue Yom

    • These results are very consistent with what we in the radiotherapy community have known for a long time. A couple dozen randomized trials have showed that single-fraction radiotherapy is very effective — and probably as effective over the short term as multiple-fraction radiation — so it is a very useful tool for patients who have a short life expectancy. The American Society for Radiation Oncology (ASTRO) stated in its Choosing Wisely guidelines that we are to avoid palliative radiation therapy that would be over 10 fractions. ASTRO guidelines for palliative radiation for bone metastases generally have recommended shorter courses, although four different regimens are allowable from 1 to 10 fractions. Those guidelines do not specify that a single-fraction radiation course is the absolute best, but there are reasons why it is prudent to maintain some latitude for physicians to be able to treat in an alternative manner for specific cases.

      We should note that the research in this instance included a majority of patients who were fully ambulatory or able to walk with a cane. That is a particular class of patients who probably don’t have very advanced involvement of the spine and for whom a limited treatment is likely to be very effective in the short term. However, they have a very good performance status and don’t have a lot of issues with mobility. For them, five fractions or maybe even 10 fractions would not actually be that taxing and could contribute to avoidance of a repeat radiation course or even give them a slightly longer survival. It’s true that nobody wants to keep people in the radiation department for days and days on end, and if I were a person with incurable cancer, I would not want to spend 44 days in the radiation department. But the difference between one fraction versus five fractions is a relatively small difference in convenience as opposed to the greater extreme of 10 fractions or 20 fractions. There is a small range within which it seems acceptable for these patients to come for 1 day, 3 days or 5 days, and the question becomes really complicated because we’re dealing not only with patients’ individual performance status and life expectancy, but also their expectations for how effective and durable the treatment will be, the possibility of not having to ever come back to radiation in the future, and the personal preferences of the patient and their family.

      The number of fractions delivered, at least in our current health care reimbursement system, does tie to the overall return. One fraction would pay somewhat less than five fractions, although the difference between one fraction and five fractions is probably not as important as how the radiation is delivered. If we utilize a simple single-field or double-field plan — as opposed to multiple beams with a stereotactic imaging verification — then you’re talking about a real difference in cost.

      We have the complicating issue of patients who are on immunotherapy, and the possibility that stereotactic radiation , or higher doses of radiation, may interact and enhance the response to immune modulators. For a patient with oligometastatic disease and good performance status, this may be an issue to explore in the future.

      Given the increasing molecular classification of disease, certain patients — particularly those with breast cancer or lung cancer with good-prognosis molecular markers on appropriate systemic therapies — may live much longer. Those may be the patients for whom a more durable treatment course may be the right answer. That cannot be addressed in a trial like this right now because we don’t have enough stratification information available, but it’s something we’re going to have to explore further in the future. We are going to have to go beyond the general cancer type and consider where the patient is in the course of disease progression and what types of more sophisticated prognosis estimations we can bring to bear for each patient.

      When the ASTRO guidelines on palliative bone irradiation came out, there was quite a bit of debate as to whether the society should have come down more firmly on the side of single fraction. It did not. It allowed some latitude in the choice, although we are discouraged from excessively extending the treatment course for these lesions. The weight of the evidence at this point probably does support single fraction plans for most cases. Radiation oncologists should be aware of that and should consider that very seriously when treating these patients.

      There is still a lot of work to be done in terms of defining what kinds of setups are appropriate for these patients, what kinds of technical specifications are appropriate, and also if we can distinguish more clearly in terms of prognosis between different categories of patients. That type of research would provide much more specific guidance. Most radiation oncologists are not trying to treat with longer fractionation on purpose. We all recognize the value of time at home, and no one wants to hold patients hostage in the basement. But most doctors will feel a responsibility to their individual patient, more so than to a guideline or a study. We must give radiation oncologists better information about how to stratify these individual patients more effectively so that they feel confident in the treatment plan they are giving them.

      One final aspect that is important to consider is how patients’ decision-making processes are affected by discussions with their physicians. The evidence indicates that most patients attribute more value to their treatments than may actually be the case, and most patients would rather feel hope in the face of terminal illness than not. It is really important that physicians are very precise and specific about what the goals are of a specific treatment, what the limitations are, and what can realistically be expected in terms of the overall disease course from that treatment.

      • Sue Yom, MD, PhD, MAS
      • UCSF Helen Diller Family Comprehensive Cancer Center
    • Disclosures: Yom reports no relevant financial disclosures.

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