The initial application, the strength is full: the superior curative effect of Disumab, helps the sustained benefit of lung cancer bone metastasis

*It is only for medical professionals to read for reference.
The treatment of bone metastases from lung cancer by Disumab can take effect quickly and bring more benefits to patients.

Bone metastasis is a common refractory complication of lung cancer patients, with an incidence of about 10%-15%.
The survival time of patients after bone metastasis is significantly shortened, and the median survival time is only 6 months to 10 months.
After treatment, 1 The annual survival rate is only 40%-50%.

Bone-related events (SREs) caused by bone metastases, such as bone pain, pathological fractures, spinal cord compression, hypercalcemia and pain caused by related treatments, also seriously affect the quality of life of patients [1].

Therefore, while controlling the primary disease, it is particularly important to actively prevent and treat bone metastases SREs.

 This case was provided by Professor Zhou Yixin from the Cancer Center of Sun Yat-Sen University.
The patient received disulumab treatment at the early stage of diagnosis.
After the treatment, the bone quality of the patient improved rapidly, and the blood calcium, blood phosphorus, and alkaline phosphatase levels returned to normal, and pain Continuous relief.

 Case brief introduction ■ General situation A 53-year-old male patient presented to the clinic in January 2020 due to "coughing with pain in the right hip and numbness in the soles of both feet" in January 2020.

Personal history: Smoking for 36 years, 10-20 cigarettes/day, quit smoking for 1 month.

Past history, family history: nothing special.

Physical examination: ECOGPS 1 point pain score: VAS 7 points Figure 1.
Pain score scale ■ Laboratory examination Routine biochemical examination (February 5, 2020): high calcium, high phosphorus, high alkaline phosphatase, in line with bone metastasis.

 Table 1.
Routine biochemical examination on February 5, 2020.
Chest CT scan + enhanced examination: right lower lung nodule, increased metabolism, considering primary malignant disease; right hilar and mediastinal 4R area with multiple enlarged lymph nodes, increased metabolism, Consider transferring.Figure 2.
Chest CT scan and craniocerebral MR plain scan + enhancement (February 5, 2020): There are several nodules in the left frontal lobe, left temporal lobe, and bilateral occipital lobe.
The diameter is about 2mm×2mm-12mm× 7mm, T1WI showed a little low signal, T2WI showed a little high signal, obvious nodular or circular enhancement after enhancement, some long slices of T1 and T2 signals were seen in the brain parenchyma around the lesion, and no lesions were seen after enhancement.

There were no space-occupying lesions in the brain stem and cerebellar hemisphere.

The ventricular system is symmetrical, with no compression, deformation, or displacement, and the midline structure is in the middle.

No clear signs of damage were seen in the skull signal.

 Figure 3.
Brain MR examination.
Pelvic CT scan + enhanced (February 5, 2020): The right anterior superior iliac spine is destroyed, metabolism is increased, and metastasis is considered.

 Figure 4.
Pelvic CT examination PET-CT (February 7, 2020): Lumbar 10 vertebral body bone metastases, invading the spinal canal.

 Figure 5.
PET-CT examination Pathological biopsy (February 11, 2020): (Right lung mass) biopsy and diagnosis combined with immunohistochemical results, the lesion is consistent with poorly differentiated adenocarcinoma.

Immunohistochemical results: CK7(+), TTF-1(+), NapsinA(+), CK5/6(-), p63(-), p40(-), ALK(D5F3)(-), ALK-N (-).

Genetic examination: negative driver gene, TMB 13 muts, PD-L1TPS 50% (22C3).

 ■Clinical diagnosis: Peripheral right lower lung poorly differentiated adenocarcinoma with right hilar, mediastinal lymph nodes, right iliac bone and vertebral body, cranial multiple metastases cT2N2M1 stage IV EGFR, ALK wild-type PD-L1 50%.

Treatment process ■ Two-pronged treatment-primary lesion treatment: immune + targeted first-line treatment, stable control of the disease.
Patients require "no chemotherapy treatment".
On February 23, 2020, tislelizumab 200mg Q3W + Anlotin will be administered 12mg QD, D1-14 first-line treatment. After 2 courses of treatment, chest CT plain scan + enhanced review showed that the lower right lung mass was smaller than before, and the hilar and right lower paratracheal lymph nodes were smaller than before.
The curative effect was evaluated as partial remission (PR).

After 8 courses of treatment, the lesions showed irregular soft tissue shadows, which should be changed after treatment; hilar lymph nodes were further reduced.

After that, the reexamination of the lesion was stable, and the PR continued until now.

 Figure 6.
CT re-examination results after tislelizumab + anlotinib treatment.
Craniocerebral MR after 8 cycles of treatment: some of the left frontal lobe, left temporal lobe, and bilateral occipital lobe metastases disappeared, and some of the lesions shrank , The largest lesion was reduced from 12mm to 7mm.

 Figure 7.
Results of craniocerebral MR re-examination after tislelizumab + anlotinib treatment ■ Quick and quick decision-anti-bone metastasis treatment: Disulizumab was initially applied, and it took effect quickly and was given on February 23, 2020 120mg of desulumab was injected subcutaneously q4w for anti-bone metastasis treatment.

After 2 courses of treatment with disulfumab, the osteolytic bone destruction of the right iliac bone was improved, and the abnormal concentration of vertebral body radioactivity was reduced; after 8 courses of treatment, the local soft tissue shadow disappeared, and the osteogenesis was obvious, and the vertebral body radioactivity distribution was not obvious.
Abnormal (SUV about 15 before treatment).

 Figure 8.
Imaging examinations before and after treatment with desulzumab.
After 1 month of treatment with 120 mg of desulzumab (March 22, 2020), the re-examination of calcium, phosphorus, and alkaline phosphatase were normal.

The reexamination was normal in the second and third months of treatment.

 Table 2.
One month after treatment with desulumab, routine biochemical re-examination before treatment without analgesics pain score: 7 points; after 2 months of treatment without analgesics pain score: 2 points; no after 6 months of treatment Pain score for the use of analgesics: 0 points Figure 9.
Pain score curve of patients before and after treatment with desulumab.
Case summary and reflections.
This patient was diagnosed with advanced lung cancer with multiple brain and bone metastases.
In view of the patient's request for no chemotherapy For treatment, I was given first-line treatment with anti-angiogenic drugs and immunization combined with anti-bone metastasis therapy to relieve pain symptoms and reduce the occurrence of bone metastases SREs.

 The patient obtained PR after 2 courses of immunization combined with anti-angiogenic drugs, and the PR has remained stable until now.

In the treatment of bone metastases, the patient's blood calcium, blood phosphorus, and alkaline phosphatase returned to normal after 1 month of treatment with desulumab, and the bone destruction was significantly improved after 2 cycles, and the pain score was also reduced from 7 to 2 , The pain symptoms disappeared after 6 months of treatment, and there was no obvious abnormality in the vertebral body radioactivity distribution after 8 cycles.

On the whole, desulumab is effective in treating lung cancer bone metastases, and it is easy to use.
It can be used as a recommended drug for the treatment of patients with lung cancer bone metastases.

BSAP (bone specific alkaline phosphatase), etc.
can be monitored during the use of desulumab, and uNTX, β-gel-linked degradation products (β-CTX) can be monitored if conditions permit.

Case provided by Doctor Zhou Yixin, Deputy Chief Physician of Sun Yat-sen University Cancer Center, Mainly engaged in the comprehensive treatment of solid tumors such as lung cancer and digestive system tumors, Deputy Chairman of the Immunotherapy Branch of Guangdong Health Care Association, Member of the Oncology Critical Care Committee of Guangdong Thoracic Disease Society Guangdong Member of the Brain Metastasis Professional Committee of the Provincial Thoracic Tumor Research Association Member of the Standing Committee of the Public Nutrition Society of Guangdong Nutrition Society Member of the Standing Committee of the Guangzhou Anti-Cancer Association Tumor Microenvironment Professional Committee 2020 CSCO "The 35 most promising young oncologists in the country" served as the reviewer of several journals such as Lung cancer The author presided over 1 National Natural Science Foundation Youth Project, 1 Provincial Natural Science Foundation General Project, and 1 Guangdong Medical Research Fund.
As the first author, he published multiple SCI articles in SITC official journals.
Among them, IF>10 points 4 articles.
IF>100 points Expert comment In recent years, with the advancement of treatment methods and technology, the 5-year survival rate of patients with advanced lung cancer has gradually increased.
However, while patients benefit from survival, the risk of bone metastasis and SREs has also increased.

46% of lung cancer patients with bone metastases will have SREs.
Once SREs occur, their survival period will be significantly shortened.
Studies have shown that survival time can be shortened by half.

If combined with severe SREs, such as hypercalcemia, pathological fractures, spinal cord compression and other complications, the patient's survival will be further shortened [1].

The RANKL/nuclear factor kappa B receptor activator/osteoprotegerin (RANKL/RANK/OPG) signaling pathway plays an important regulatory role in tumor bone metastasis, and early blocking of this pathway can effectively prevent the occurrence of SRE.

The RANKL inhibitor desulumab can block the RANKL/RANK/OPG signaling pathway by specifically binding to RANKL, and play a preventive and preventive effect on bone metastases SRE [2].

Study 224 showed that compared with patients in the zoledronic acid group, the median overall survival (OS) of lung cancer patients treated with desulumab was significantly prolonged, and the survival of patients with non-small cell lung cancer (NSCLC), especially lung squamous cell carcinoma The benefits are the most significant [3].

Based on the excellent clinical research data of desulimab, the National Comprehensive Cancer Network (NCCN) guidelines and the European Society of Medical Oncology (ESMO) guidelines both recommend desulumab for the treatment of lung cancer bone metastases [1].

At present, as an indication for bone-modifying drugs, desulimab has been approved for marketing in China and has been included in the national medical insurance catalog, which greatly reduces the economic burden of patients.

In addition, compared with bisphosphonates (intravenous injection) traditional bone-modifying drugs, the use of disulumab is more convenient (subcutaneous injection), and it is not cleared by the kidneys, so it will not cause additional burden on the kidneys.

 In this case, blood calcium, blood phosphorus, and alkaline phosphatase levels quickly returned to normal after treatment with desulumab, the pain symptoms were significantly relieved, and the metabolism of bone metastases decreased, showing that desulumab is good for bone metastasis and bone pain Efficacy, we also look forward to more clinical research results in the future to guide the rational optimization of medication regimens.

Comment on the expert profile Professor Zhang Bei, Director of the Department of Comprehensive Traditional Chinese Medicine, Sun Yat-sen University Tumor Hospital, Member of the Standing Committee of the 12th and 13th National People’s Congress of Guangdong Province Member of the Educational, Science, Culture and Health Committee of Guangdong Provincial People’s University Member of the School Council of Sun Yat-sen University Famous Doctor of Sun Yat-sen University, Guangdong Province Famous TCM doctors, national famous old TCM instructors, instructors of the first batch of famous TCM physicians in Guangdong Province, undertaking project instructors, standing committee members of the Chinese Society of Traditional Chinese Medicine Oncology Committee, standing members of the Guangdong Association of Integrative Medicine, standing directors of the Guangdong Society of Traditional Chinese Medicine, Guangdong Province, Chinese and Western medicine Chairman of the Oncology Professional Committee of the Integrative Society, Chairman of the Traditional Medicine Professional Committee of the Guangdong Anti-Cancer Association, Vice Chairman of the Oncology Professional Committee of the Guangdong Chinese Medicine Society, Deputy Chairman of the Professional Committee of Integrated Traditional Chinese and Western Medicine, Guangzhou Anti-Cancer Association, Guangdong Provincial Party Committee Health Expert, Guangdong Province Evaluation expert of the Drugs and Food Supervision Administration, Medical Malpractice Technical Appraisal Expert of Guangdong Medical Association, Vice President of the Medical Achievement Transformation Application Branch of Guangdong Medical Management Association Reference: [1] Expert consensus on the diagnosis and treatment of lung cancer bone metastasis (2019 edition).
Chinese Journal of Lung Cancer.
2019;22(4):187-207.
[2] Schwarz EM, Ritchlin CT.
Clinical development of anti-RANKL therapy.
Arthritis Res Ther.
2007;9 Suppl 1(Suppl 1):S7.
[3] Scagliotti GV, Hirsh V, Siena S, et al.
Overallsurvival improvement in patients with lung cancer and bone metastases treated with denosumab versus zoledronic acid: subgroup analysis from a randomizedphase 3 study.
J Thorac Oncol.
2012 Dec;7(12):1823-1829.
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