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: Unknown

180 Participants Needed

Trial Summary

What is the purpose of this trial?

Bone is a common site of metastasis for a range of malignancies. Bone metastases have the potential to cause significant morbidity including pain, impairment of ambulation and reduced functional independence. Previous research has shown that pathological fractures are observed in 9 to 29 percent of patients with long bone metastases, and a high proportion of these require surgical intervention to relieve pain and restore function. The goal of this study is to describe the clinical outcomes of patients with femoral metastases at high risk of pathological fracture. Patients referred for treatment of femoral metastases at high risk of fracture will be followed prospectively after undergoing with surgery (± post-operative radiotherapy), or radiotherapy alone. Patient and disease characteristics, ambulatory status and limb function will be documented before treatment. These Clinical outcomes of participants in each treatment group will be measured 6 weeks after treatment, and 3- and 6 months after enrolment, with particular reference to patient-reported outcomes relating to pain, ambulatory status, limb function and quality of life.

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.

What data supports the idea that Surgery Alone vs Surgery + Radiation for Bone Cancer is an effective treatment?

The available research shows that combining surgery with radiation and zoledronic acid, a drug used to strengthen bones, can be effective for treating bone cancer. One study found that using zoledronic acid with radiotherapy helped manage bone cancer that had spread, reducing the risk of fractures and improving patient outcomes. Another study indicated that this combination could be beneficial for patients with bone metastases from lung cancer, as it reduced fracture risk and potentially improved survival. These findings suggest that adding radiation and zoledronic acid to surgery might offer better results than surgery alone for bone cancer. ^{1 2 3 4 5}

What safety data exists for surgery and radiation treatment for bone cancer?

The research primarily discusses the safety and efficacy of zoledronic acid (ZA) in combination with chemotherapy for bone metastases, not specifically for surgery and radiation treatment for bone cancer. ZA is shown to be safe and effective in reducing skeletal-related events in various cancers, including osteosarcoma and genitourinary cancers. It is well tolerated with long-term use and has been used in combination with chemotherapy in metastatic osteosarcoma. However, specific safety data for the combination of surgery and radiation in bone cancer is not directly addressed in the provided studies. ^{3 6 7 8 9}

Is Surgery Alone (also known as the drug Zometa) a promising treatment for bone cancer?

The research suggests that Zometa, a drug used in combination with other treatments, can help manage bone cancer by reducing complications like fractures and improving survival in patients with bone metastases. However, the studies focus on its use with other therapies, not as a standalone treatment. ^{2 5 10 11 12}

Research Team

Rebecca Wong, M.D.

Principal Investigator

University Health Network, Princess Margaret Hospital

Peter Ferguson, MD

Principal Investigator

Mount Sinai Hospital, Canada

Eligibility Criteria

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)

At least 18 years of age

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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]

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]

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]

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]

References

1. China pubmed.ncbi.nlm.nih.gov

[Clinical analysis of therapeutic effect of zoledronic acid combined with radiotherapy for metastatic bone cancer]. [2018]

2. England 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. [2019]

3. England 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. [2021]

4. Australia pubmed.ncbi.nlm.nih.gov

Radiotherapy, Bisphosphonates and Surgical Stabilization of Complete or Impending Pathologic Fractures in Patients with Metastatic Bone Disease. [2022]

5. England 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. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Zoledronic acid in metastatic osteosarcoma: encouraging progression free survival in four consecutive patients. [2022]

7. England pubmed.ncbi.nlm.nih.gov

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

8. United States pubmed.ncbi.nlm.nih.gov

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

9. England pubmed.ncbi.nlm.nih.gov

Under usage of zoledronic acid in non-small cell lung cancer patients with metastatic bone disease--a short communication. [2018]

10. Italy pubmed.ncbi.nlm.nih.gov

Zoledronic acid and radiation: toxicity, synergy or radiosensitization? [2021]

11. England pubmed.ncbi.nlm.nih.gov

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

12. Scotland pubmed.ncbi.nlm.nih.gov

Successful percutaneous treatment of bone tumors using microwave ablation in combination with Zoledronic acid infused PMMA cementoplasty. [2020]