Community Voice Palliative Care

One and Done: 3 Reasons Why Single Fraction Should Be Standard to Palliate Simple Bone Metastasis

Single fraction treatment of painful bone metastases is as effective as multi-fraction regimens, less costly, and more convenient for patients. It should be the standard of care for the palliation of bone metastases. ASTRO favored shorter treatment rather than single fraction in its “Choosing Wisely” program, while the American Academy of Hospice and Palliative Medicine included the recommendation, saying “Although it results in a higher incidence of later need for retreatment (20% vs 8% for multi-fraction regimens), the decreased patient burden usually outweighs any considerations of long-term effectiveness for those with a limited life expectancy”.  But instead of just reading policy statements, let’s look at the evidence.

 

1. Efficacy.  In the RTOG trial comparing 8 Gy in1 fraction to 30 Gy in 10 fractions showed no difference in the rate for complete and partial pain relief (overall 66% in each group). At 3 months, 33% of the 898 patients no longer required narcotic pain medication, and this did not differ between treatment arms. The multi-fraction treatment had greater grade 2-4 toxicity (17% vs 10%). The rate of retreatment was higher (18% vs 9%), but it had nothing to do with efficacy – physicians were re-irradiating their single fraction treated patients basically because they could – even though their patients were just as likely to have pain control and not need narcotics.

Dutch trial comparing 8 Gy in 1 fraction to 24 Gy in 6 fraction in 1171 patient had similar results – equal efficacy, with a higher retreatment rate (24% vs 7%). After controlling for the influence of re-treatment, they found that single fraction and multi-fraction treatment provided equal palliation, but although there was no greater acute toxic toxicity, there was a small increase in the number of pathologic fractures (not demonstrated in other trials). The predictors for retreatment were not uncontrolled pain or increased use of narcotics in single fraction treated patients. The randomization arm itself significantly predicted re-treatment.

The British/New Zealand trial compared 8 Gy/1 fx, 20 Gy/5 fx, 30 Gy/10 fx, at 12 months for 765 patients, There were no differences in pain end points amongst the three groups – all had a 78% response rate and no difference in toxicity. Time to first improvement in pain, time to complete pain relief, and time to first increase in pain were similar in all arms. All studies confirmed RTOG’s results for retreatment – it was based on physician comfort to retreat, not lack of efficacy.

 

2. Cost.  The RTOG re-analyzed the data to evaluate cost-effectiveness of single fraction treatment. The expected mean cost for a course of single fraction treatment was $1009 versus $2322 for a course of multi-fraction treatment. However, they did not report the outcome including the additional cost of re-treatment. The Dutch group also reviewed the costs and found that even when accounting for re-treatment, the single fraction course was less costly – $2438 vs $3311.

 

3. Convenience.  I calculated how many fractions the average patient treated with single fraction versus multi-fraction treatment, including the retreatment. To make it as fair as possible, the presumed retreatment schema for single fraction patients would be 30 Gy in 10 fractions, while those re-treated after 30 Gy in 10 fractions would receive a single fraction of 8 Gy. Looking at all three trials, the “average” single fraction patient would like receive 2.8-3.8 fractions compared to 10.1 fractions for the multi-fraction approach.

 

Keep in mind, this data may not apply for all bone metastases. If there is spinal epidural disease or a significant soft tissue mass from the tumor, that’s a different story. Maybe that’s why ASTRO hedged. But if it’s a simple problem, the solution should be simple, too.

The evidence reveals that single fraction palliative radiation is equally effective, less costly and more convenient. So why isn’t it standard of care? What do we need to do to make it the standard?

  • subatomicdoc

    Thanks for this post, Simul. It’s important to discuss how we can best help patients. The evidence supports a ‘less is more’ approach.

  • John Adler

    I agree and would urge you to rework your “review” of the topic here
    to be published in Cureus.com. Publication is free and you’ll get >2 order of magnitude more readers!

  • Simul Parikh

    Thank you Dr Adler. What do you mean “rework my review”?

  • John Adler

    Take your ideas and back them up with references, and recompile these writings in a formal review paper and then publish it in Cureus. You’ll reach a bigger audience and its free!

  • subatomicdoc

    Thanks for your interest in Simul’s post and in Radiation Nation. However, I’d appreciate if you comment on the content here rather than trying to only encourage reposting content for your website. Thanks!
    Matt

  • John Adler

    The evidence in support of single fraction radiation for a range of indications, especially bone metastases, has been around for a generation. In fact there is growing evidence that it is the equivalent if not much better than conventional fractionation for a number of primary tumors including lung, renal. liver and maybe even prostate. However, here Dr. Subatomic, we are merely 3 people talking to ourselves……I don’t see much sense in that. If Simul wants to reach a meaningful audience outside the 3 of us, I am giving him a chance on Cureus, which greatly simplifies the process of publishing peer reviewed concepts and its free. If one is going to the effort of starting a discussion like this, why not try to have an impact? But heck if you Dr. Subatomic like the idea of talking to yourself, I have no desire to stop you.

  • subatomicdoc

    Dr. Adler, please feel free to call me Matt, that’s why I put it into my last comment.

    Let me clarify: when I asked you to “comment on the content here” I meant that it would polite to discuss the topic the author took time to write about before trying to get him to reshare on your website.

    Actually, I fully support reposting and do it myself. It’s a great way to disseminate a well-crafted message, which Simul has done. Typical etiquette is to recognize where it was reposted from, so why would I object? That only further raises awareness of Radiation Nation, which is doing pretty well for just a few posts. I’m pleased to see you here, Dr. Adler – it’s a sign we’re on the right track.

    Dr. Adler, if you wish to share your experience with stereotactic radiation for oligometastic bone metastases here that would be wonderful. But I appreciate that you have now commented some on Simul’s topic. Simul, if you want any help reposting on Cureus or anywhere else just let me know.

  • John Adler

    Cool…keep up the good work!

  • Steve Wilson MD

    The idea that retreatment was not due to lack of pain control but was done “just because they could retreat” makes no sense to me. If the pain is controlled there’s no need to retreat, and thus retreatment indicates failure of pain control in the first place. Is it just me to whom that makes no sense? Can you quote from the trials cited above the concept of “We retreated just because we could?” so I can see how it was explained in the original journal articles? Something smells to high heaven in Denmark about this issue…

  • Simul Parikh

    Dr. Wilson,

    I was a resident at UPMC back in the day and we did some cancer screening in the Amish population together 🙂 Good to hear from you and thanks for reading!

    This is from the RTOG, and I apologize for the length. They used the BPI, which is the same tool that Dr. Dwight Heron utilized at UPMC for bone mets. The other trials found the exact same results, so I’ll just use this one as the example of how this was cited.

    “The Brief Pain Inventory was complete in 845 patients at the time of study entry. The 3-month Brief Pain Inventory assessment was completed by 573 of the 845 patients; the reasons for missing Brief Pain Inventory at 3 months included patient death (128 patients), patient refusal or too ill to complete (32 patients), institutional error or late form (40 patients), patient not seen (36 patients), and other or unknown reasons (36 patients). A complete response was observed in 17% (93 patients) of the 573 patients, and partial response was observed in 49% (280 patients), for an overall response rate of 66% (375 of 573 patients); only 10% (55 patients) of the 573 patients had progression of pain (Table 3). A 3-month Brief Pain Inventory assessment was available for 288 patients in the 8-Gy arm and 285 patients in the 30-Gy arm; the complete response and partial response rates for the 288 patients in the 8-Gy arm were 15% (44 patients) and 50% (143 patients), respectively, and for 285 patients in the 30-Gy arm were 18% (51 patients) and 48% (137 patients) (P = .6). For patients treated to a solitary painful site , the complete response and partial response rates were 18% (29 patients) and 52% (85 patients) for the 165 patients in the 8-Gy arm and 21% (32 patients) and 51% (79 patients) for the 156 patients in the 30-Gy arm (P = .17). At 3 months, 33% of patients no longer required narcotic medications (Table 4). No difference in response at 3 months was observed between the two treatment arms when stratified by number of painful treatment sites, weight-bearing status, pretreatment pain score, or whether the patient was receiving bisphosphonates (Table 5). In addition, there was no difference in response rate between the treatment arms at 3 months when we used the international consensus end points for complete response (pain score of zero with stable or reducing analgesic intake), with a complete response rate of 10% (25 patients) for the 256 patients in the 8-Gy arm and 12% (31 patients) for the 255 patients in the 30-Gy arm with 3-month BPI and adequate information on narcotic usage…

    The decision to re-treat a patient was left to the discretion of the treating physician. A statistically significant difference was observed in retreatment rates between the two arms, with twice as many patients in the 8-Gy arm receiving retreatment (3-year retreatment rates: 18% [76 of the 449 patients] in the 8-Gy arm and 9% [33 of the 432 patients] in the 30-Gy arm; P<.001). The difference in retreatment rates was apparent by 3 months after the initial treatment. Most of the retreatment was given in the first 9 months after the initial treatment, and retreatment was rarely performed more than 1 year after the initial treatment."

    So, if …

    1) The pain reduction score in all trials is the same regardless of what the fractionation at 3 months

    2) The duration of pain reduction score in is the same regardless of what the fractionation is the same

    3) The re-treatment rates begin to differ at 3 months.

    Then, what would be rationale for re-treatment other than just feeling that 8 Gy wasn't good enough? I can't come up with any other reason, but I'd love to hear your hypotheses and I hope UPMC is treating you well.

    Simul