Surgery Alone vs Surgery + Radiation for Bone Cancer

Recruiting at 1 trial location

Overseen By Rebecca Wong, MB ChB

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Disqualifiers: Lymphoma, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

Duration: 6 weeks

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether surgery alone or surgery with radiation therapy better treats bone cancer that has spread to the femur and is at high risk of breaking. Researchers aim to determine which treatment more effectively reduces pain, improves walking ability, and enhances daily life. Candidates include individuals with a confirmed cancer diagnosis, excluding lymphoma, and femoral metastases at high risk of fracture. The study tracks patients' recovery and quality of life at several points over six months. As an unphased trial, it offers patients the chance to contribute to important research that could improve future bone cancer treatment options.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining surgery with radiation therapy can manage symptoms and control tumors more effectively. This approach is generally safe and may reduce the risk of complications. Studies indicate that a type of radiation called SBRT is safe and effective for treating bone cancer. Therefore, using both surgery and radiation together should be well-tolerated by patients. It is important to discuss any concerns with the medical team before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the combination of surgery and radiation therapy for bone cancer because it offers a potentially more effective approach than surgery alone. While surgery is a common treatment to remove tumors, adding radiation therapy could help target any remaining cancer cells, reducing the risk of the cancer coming back. This combination might improve long-term outcomes and enhance overall survival rates for patients. By integrating these two methods, the treatment aims to maximize cancer control while minimizing the chances of recurrence, giving patients a better chance at recovery.

What evidence suggests that this trial's treatments could be effective for bone cancer?

This trial will compare the effectiveness of Surgery Alone versus Surgery combined with Radiation Therapy for treating bone cancer. Studies have shown that using both surgery and radiation therapy can effectively treat bone cancer, especially when it has spread to the bones. Research indicates that patients who receive both treatments and respond well can achieve a 5-year survival rate as high as 90%. One study found that stereotactic body radiation therapy (SBRT) is safe and effective for individuals with recurring or spreading osteosarcoma, a type of bone cancer. While surgery alone can help save the limb, adding radiation seems to improve survival chances. Overall, combining these treatments offers a promising way to manage bone cancer that has spread to the thigh bone (femur). ^{4 6 7 8 9}

Who Is on the Research Team?

Rebecca Wong, M.D.

Principal Investigator

University Health Network, Princess Margaret Hospital

Peter Ferguson, MD

Principal Investigator

Mount Sinai Hospital, Canada

Are You a Good Fit for This Trial?

This trial is for adults with a confirmed cancer diagnosis, who have bone metastases in the femur at high risk of breaking (Mirels' score ≥8). Participants must be able to give consent and commit to follow-up. It's not suitable for individuals with lymphoma or those unable to participate.

Inclusion Criteria

Histologically confirmed diagnosis of malignancy other than lymphoma

Presence of femoral metastases at high risk of pathologic fracture (Mirels' score 8 or more)

Able to provide written informed consent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo surgery with or without post-operative radiotherapy, or radiotherapy alone for femoral metastases at high risk of fracture

6 weeks

1 visit (in-person) for surgery or radiotherapy

Follow-up

Participants are monitored for clinical outcomes, including pain, ambulatory status, limb function, and quality of life

6 months

Assessments at 6 weeks, 3 months, and 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Combined Surgery and Radiation therapy
• Surgery Alone

Trial Overview

The study compares two approaches for treating patients with high-risk femoral bone metastases: one group will receive surgery followed by radiation therapy, while another group will undergo surgery alone. The focus is on pain relief, mobility, limb function, and life quality after treatment.

How Is the Trial Designed?

Group I: Surgery + Radiation Therapy Active Control 1 Intervention

Group II: Surgery Alone Active Control 1 Intervention

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Published Research Related to This Trial

Microwave ablation combined with Zoledronic acid (ZA) was used to treat unresectable bone tumors in 4 patients, demonstrating a novel approach for cases where traditional surgical resection is too risky or impossible.

This method was applied to patients with various conditions, including giant cell tumors, multiple myeloma, and breast cancer metastasis, suggesting its potential versatility in treating complex bone tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful percutaneous treatment of bone tumors using microwave ablation in combination with Zoledronic acid infused PMMA cementoplasty. Luna, LP., Sankaran, N., Ehresman, J., et al.[2020]

In a study of 9,874 lung cancer patients with bone metastases, treatment with Zometa (zoledronic acid) significantly reduced fracture risk by 40% compared to those not receiving intravenous bisphosphonates, with even short-term use (31-90 days) showing a 47% reduction in fracture risk.

Patients treated with Zometa also experienced lower mortality rates, with a mean of 38.6 deaths per 100 person-years compared to 46.8 for those not treated with Zometa, indicating that longer treatment duration leads to better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective evaluation of the clinical benefit of long-term continuous use of zoledronic acid in patients with lung cancer and bone metastases. Henk, HJ., Kaura, S., Teitelbaum, A.[2019]

The study determined that zoledronic acid (ZA) can be safely combined with conventional chemotherapy in patients with metastatic osteosarcoma, with a maximum tolerated dose (MTD) established at 2.3 mg/m² (max 4 mg).

Out of 24 patients treated, five experienced dose-limiting toxicities, but there were no significant concerns regarding renal toxicity or osteonecrosis of the jaw, indicating a favorable safety profile for ZA in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and dose discovery analysis of zoledronic acid with concurrent chemotherapy in the treatment of newly diagnosed metastatic osteosarcoma: a report from the Children's Oncology Group. Goldsby, RE., Fan, TM., Villaluna, D., et al.[2021]

Postoperative radiotherapy (RT) after orthopedic stabilization significantly improves local tumor control and pain management in patients with metastatic bone disease, as shown in a study of 72 patients with a median follow-up of 9 months.

The use of bisphosphonates alone did not reduce the need for RT, and while combining bisphosphonates with RT may enhance local control, it is not a substitute for RT in managing bone metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy, Bisphosphonates and Surgical Stabilization of Complete or Impending Pathologic Fractures in Patients with Metastatic Bone Disease. Wolanczyk, MJ., Fakhrian, K., Adamietz, IA.[2022]

In a study of 114 patients with stage IV non-small cell lung cancer (NSCLC) and metastatic bone disease (MBD), only 37.7% received zoledronic acid (ZA) alongside their first chemotherapy treatment.

Patients who received ZA with chemotherapy (ZCt) had significantly better overall survival, with a median of 34 weeks compared to 19 weeks for those who received chemotherapy alone, suggesting that ZA may enhance treatment outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Under usage of zoledronic acid in non-small cell lung cancer patients with metastatic bone disease--a short communication. Calderone, R., Nimako, K., Leary, A., et al.[2018]

In a study of 45 patients with limited metastatic bone cancer, combining zoledronic acid with local radiotherapy resulted in a significantly higher rate of bone recalcification (52.2%) compared to radiotherapy alone (22.7%).

The combination therapy also reduced the formation of new bone metastases (13.0% in the combination group vs. 40.9% in the radiotherapy alone group), indicating a potential benefit in managing metastatic bone cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical analysis of therapeutic effect of zoledronic acid combined with radiotherapy for metastatic bone cancer]. Cheng, J., Xue, J., Wu, HG., et al.[2018]

Zoledronic acid (Z) enhances the effectiveness of ionizing radiation (IR) in non-tumoral cells, showing a synergistic effect when used in combination, particularly when Z is administered after radiation exposure.

While high concentrations of Z are toxic, clinically recommended doses can act as a radiosensitizer, increasing cytotoxic effects on cells and leading to greater chromosome damage when given post-irradiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zoledronic acid and radiation: toxicity, synergy or radiosensitization? Alcaraz, M., Olivares, A., Armero, D., et al.[2021]

In a small cohort of four patients with stage IV osteosarcoma, treatment with zoledronic acid (ZA) resulted in a median progression-free survival of 19 months and a median overall survival of over 56 months, indicating its potential efficacy as a treatment option.

Despite prolonged use of ZA for up to 5 years, the patients experienced no significant toxicities and did not require chemotherapy, suggesting that ZA may be a safe long-term treatment for metastatic osteosarcoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zoledronic acid in metastatic osteosarcoma: encouraging progression free survival in four consecutive patients. Conry, RM., Rodriguez, MG., Pressey, JG.[2022]

Denosumab significantly delays the time to first skeletal-related event and multiple skeletal-related events in patients with bone metastases compared to zoledronic acid, based on a meta-analysis of 3 randomized controlled trials involving 5723 patients.

Both denosumab and zoledronic acid show similar overall survival rates and safety profiles, but denosumab is more effective in preventing complications related to bone metastases, indicating its potential as a preferred treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of denosumab versus zoledronic acid in patients with bone metastases: a systematic review and meta-analysis. Sun, L., Yu, S.[2018]

Zoledronic acid is effective in reducing skeletal-related events (SREs) such as fractures and spinal cord compression in patients with metastatic bone disease from advanced prostate cancer or renal cell carcinoma, significantly lowering the overall risk of SREs compared to placebo.

In patients with renal cell carcinoma, zoledronic acid not only reduced SREs but also delayed the progression of bone lesions by 5 months, and it has been shown to be safe and well tolerated for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zoledronic acid is effective in preventing and delaying skeletal events in patients with bone metastases secondary to genitourinary cancers. Saad, F., Lipton, A.[2018]

Only about 23% of the 6347 patients with bone metastases from genitourinary cancers received Zometa (zoledronic acid), and there was an average delay of 108 days before treatment initiation after diagnosis.

Patients with prostate cancer who received Zometa had a significantly lower risk of fractures and longer survival compared to those who did not receive intravenous bisphosphonates, with benefits increasing with longer treatment duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of zoledronic acid treatment patterns and clinical outcomes in patients with bone metastases from genitourinary cancers. Henk, HJ., Kaura, S.[2019]

In a study of 27 patients with bone metastases from renal cell carcinoma, the combination of zoledronic acid hydrate and palliative radiotherapy resulted in a 1-year local skeletal-related event-free survival rate of 77.6%, indicating its efficacy in preventing complications associated with bone metastases.

The treatment was well-tolerated, with only mild grade 3 toxicities reported and no severe (grade 4 or 5) toxicities, suggesting a favorable safety profile for this combined approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of palliative radiotherapy combined with zoledronic acid hydrate for metastatic bone tumour from renal cell carcinoma. Harada, H., Shikama, N., Wada, H., et al.[2021]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10416357/

Radiotherapy in bone sarcoma: the quest for better treatment ...

Results showed an overall survival and a progression-free survival of 68% and 45%, respectively (2b).

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12274193/

Systemic strategies for osteosarcoma: advances and future ...

Although surgery has become more limb-preserving, the overall prognosis remains challenging, with a 5-year survival rate of 60–70% for localized ...

3.

consultqd.clevelandclinic.org

consultqd.clevelandclinic.org/new-study-supports-sbrt-as-safe-effective-for-osteosarcoma

New Study Supports SBRT as Safe, Effective for Osteosarcoma

New analysis showed that stereotactic body radiation therapy (SBRT) is both a safe and effective treatment for recurrent and metastatic osteosarcoma.

4.

nature.com

nature.com/articles/s41598-023-27476-9

Development of nomogram and discussion of radiotherapy ...

It is worth noting that the 5-year survival rate of patients who had a pronounced response during treatment reached 90%. This result suggested ...

5.

mayoclinicproceedings.org

mayoclinicproceedings.org/article/S0025-6196(11)62545-7/fulltext

Effectiveness of Radiotherapy for Osteosarcoma That ...

Excellent responses to initial neoadjuvant chemotherapy (>90% necrosis) occur in only about one half of patients; the rest seem to have predictably more ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11745020/

Radiotherapy and surgery: can this combination be further ...

Combining radiotherapy and surgery can lead to improved symptom management, optimal tumor control, and minimize the risk of morbidity. However, ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8865506/

An Analysis of Outcomes From the National Cancer ...

Four thousand four hundred thirty patients with osteosarcoma (3,435 appendicular, 810 axial, and 185 other) showed survival at 1-year, 5-year, ...

8.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0140673624018129

Safety and efficacy of pembrolizumab, radiation therapy ...

Addition of pembrolizumab to preoperative radiotherapy and surgery improves disease-free survival for patients with stage III undifferentiated pleomorphic ...

9.

bmccancer.biomedcentral.com

bmccancer.biomedcentral.com/articles/10.1186/s12885-023-11232-3

Radiotherapy in bone sarcoma: the quest for better treatment ...

Results showed an overall survival and a progression-free survival of 68% and 45%, respectively (2b).