Bone Metastasis in Gastric Cancer Patients

Jae Bong Ahn,하태경,권성준 대한위암학회 2011 Journal of gastric cancer Vol.11 No.1

Purpose: Bone metastasis from stomach cancer occurs only rarely and it is known to have a very poor prognosis. This study examined the clinical characteristics and prognosis of patients who were diagnosed with stomach cancer and bone metastasis. Materials and Methods: The subjects were 19 patients who were diagnosed with stomach cancer at Hanyang University Medical Center from June 1992 to August 2010 and they also had bone metastasis. The survival rate according to many clinicopathologic factors was retrospectively analyzed. Results: 11 patients out of 18 patients (61%) who received an operation were in stage IV and the most common bone metastasis location was the spine. Bone scintigraphy was mostly used for diagnosing bone metastasis and PET-CT and magnetic resonance imaging were used singly or together. The serum alkaline phosphatase at the time of diagnosis had increased in 12 cases and there were clinical symptoms (bone pain) in 16 cases. Treatment was given to 14 cases and it was mostly radiotherapy. There were 2 cases of discovering bone metastasis at the time of diagnosing stomach cancer. The interval after operation to the time of diagnosing bone metastasis for the 18 cases that received a stomach cancer operation was on average 14.9±17.3 months and the period until death after the diagnosis of bone metastasis was on average 3.8±2.6 months. As a result of univariate survival rate analysis, the group that was treated for bone metastasis had a significantly better survival period when the bone metastasis was singular rather than multiple, as compared to the non-treatment group, yet both factors were not independent prognosis factors on multivariate survival analysis. Conclusions: An examination to confirm the status of bone metastasis when conducting a radio-tracer test after the initial diagnosis and also after an operation is needed for stomach cancer patients, and bone scintigraphy is the most helpfully modality. Making the diagnosis at the early stage and suitable treatments are expected to enhance the survival rate and improve the quality of life even for the patients with bone metastasis

Bone Metastasis in Gastric Cancer Patients

Ahn, Jae-Bong,Ha, Tae-Kyung,Kwon, Sung-Joon The Korean Gastric Cancer Association 2011 Journal of gastric cancer Vol.11 No.1

Purpose: Bone metastasis from stomach cancer occurs only rarely and it is known to have a very poor prognosis. This study examined the clinical characteristics and prognosis of patients who were diagnosed with stomach cancer and bone metastasis. Materials and Methods: The subjects were 19 patients who were diagnosed with stomach cancer at Hanyang University Medical Center from June 1992 to August 2010 and they also had bone metastasis. The survival rate according to many clinicopathologic factors was retrospectively analyzed. Results: 11 patients out of 18 patients (61%) who received an operation were in stage IV and the most common bone metastasis location was the spine. Bone scintigraphy was mostly used for diagnosing bone metastasis and PET-CT and magnetic resonance imaging were used singly or together. The serum alkaline phosphatase at the time of diagnosis had increased in 12 cases and there were clinical symptoms (bone pain) in 16 cases. Treatment was given to 14 cases and it was mostly radiotherapy. There were 2 cases of discovering bone metastasis at the time of diagnosing stomach cancer. The interval after operation to the time of diagnosing bone metastasis for the 18 cases that received a stomach cancer operation was on average $14.9{\pm}17.3$ months and the period until death after the diagnosis of bone metastasis was on average $3.8{\pm}2.6$ months. As a result of univariate survival rate analysis, the group that was treated for bone metastasis had a significantly better survival period when the bone metastasis was singular rather than multiple, as compared to the non-treatment group, yet both factors were not independent prognosis factors on multivariate survival analysis. Conclusions: An examination to confirm the status of bone metastasis when conducting a radio-tracer test after the initial diagnosis and also after an operation is needed for stomach cancer patients, and bone scintigraphy is the most helpfully modality. Making the diagnosis at the early stage and suitable treatments are expected to enhance the survival rate and improve the quality of life even for the patients with bone metastasis.

Dissecting Tumor-Stromal Interactions in Breast Cancer Bone Metastasis

Yibin Kang 대한내분비학회 2016 Endocrinology and metabolism Vol.31 No.2

Bone metastasis is a frequent occurrence in breast cancer, affecting more than 70% of late stage cancer patients with severe complicationssuch as fracture, bone pain, and hypercalcemia. The pathogenesis of osteolytic bone metastasis depends on cross-communicationsbetween tumor cells and various stromal cells residing in the bone microenvironment. Several growth factor signalingpathways, secreted micro RNAs (miRNAs) and exosomes are functional mediators of tumor-stromal interactions in bone metastasis. We developed a functional genomic approach to systemically identified molecular pathways utilized by breast cancercells to engage the bone stroma in order to generate osteolytic bone metastasis. We showed that elevated expression of vascularcell adhesion molecule 1 (VCAM1) in disseminated breast tumor cells mediates the recruitment of pre-osteoclasts and promotestheir differentiation to mature osteoclasts during the bone metastasis formation. Transforming growth factor β (TGF-β) is releasedfrom bone matrix upon bone destruction, and signals to breast cancer to further enhance their malignancy in developing bone metastasis. We furthered identified Jagged1 as a TGF-β target genes in tumor cells that engaged bone stromal cells through the activationof Notch signaling to provide a positive feedback to promote tumor growth and to activate osteoclast differentiation. Substantiallychange in miRNA expression was observed in osteoclasts during their differentiation and maturation, which can be exploitedas circulating biomarkers of emerging bone metastasis and therapeutic targets for the treatment of bone metastasis. Furtherresearch in this direction may lead to improved diagnosis and treatment strategies for bone metastasis.

전이성 골종양의 역학적 연구

김재도,이덕희,박정호,손영찬,홍영기,손정환,Kim, Jae-Do,Lee, Duk-Hee,Park, Jeong-Ho,Son, Young-Chan,Hong, Yonng-Gi,Son, Jeong-Hwan 대한근골격종양학회 1995 대한골관절종양학회지 Vol.1 No.1

1988년부터 1993년까지 최근 6년간 고신의료원에서 전이성 골종양으로 진단받고 치료받았던 환자중 조직학적으로 확진되었던 417명의 환자를 대상으로 후향적 조사를 통하여 연령별, 성별, 골전이 부위별 분포와 원발성 암에 따른 전이의 양상을 분석하여 다음과 같은 결과를 얻었다. 1. 골전이를 가장 잘 일으키는 원발성 암은 폐암(29.5%), 위암(15.3%), 유방암(11.3%), 자궁경부암(5.3%), 간암(4.8%)등의 순이었으며, 원발 부위 미상의 전이성 골종양은 7.7%였다. 2. 연령 분포는 40대 이후에서 발생한 경우가 85.3%로 대부분을 차지하였으며, 평균 연령은 54.8세였다. 남자의 경우 50대(39.4%), 60대(27.5%), 40대(14.3%)의 순이었으며, 여자의 경우는 50대(31.9%), 40대(21.7%), 60대(20.5%)의 순으로 발생하였다. 3. 골전이 부위별 분포는 척추(25.2%), 골반골(16.0%), 늑골(15.3%), 대퇴골(14.5%), 두개골(8.3%), 상완골(5.5%), 견갑골(5.1%)등의 순이었으며, 골전이의 분포 양상은 체간골이 75.8%로 가장 많았고, 그 다음으로 근위부의 장관골이 19.8%, 슬관절과 주관절 이하의 원위 골격계가 4.4%의 순으로 나타났다. 척추 중에서는 흉추(42.1%), 요추(39.1%), 경추(13.2%), 천추(5.6%)의 순으로 나타났다. 4. 골전이 부위별 분포는 원발성 암의 종류에 관계없이 다발성 전이(73.1%)가 단발성 전이(26.9%) 보다 많았다. 5. 원발성 종양에 따른 분포 양상은 폐암의 경우 연령 분포는 50대, 60대, 40대의 순이었고, 남녀비는 2.3 : 1이었으며, 골전이는 척추, 골반, 대퇴골의 순으로 발생하였다. 위암의 경우 연령 분포는 50대, 60대, 40대의 순이었고, 골전이 부위는 척추, 대퇴골, 골반의 순이었다. 유방암의 경우 연령 분포는 40대, 50대, 30대의 순이었고, 골전이 부위는 척추, 늑골, 골반의 순이었다. 6. 원발 부위 미상의 전이성 골종양의 경우는 60대가 가장 많았으며, 30대부터 70대까지 분포되어 있었다. 골전이 부위는 척추, 대퇴골, 골반골, 늑골, 견갑골의 순이었으며, 조직학적으로는 선암, 편평세포암이 많았다. Metastatic bone tumor is the most common bone tumor and 32.5% of all primary malignant tumors are eventually metastasize to bone. Metastatic bone tumor has been more frequently encountered disease in the orthopedic fields due to the greater longevity of life of the patients with primary visceral cancers by major advances in early detection, diagnosis, and surgical/radiotherapeutic/chemotherapeutic treatment of primary and metastatic lesions. Therefore, the epidemiologic data about the incidences and the patterns of bone metastasis is important. We reviewed 417 patients who were diagnosed and treated for metastatic bone tumor at Kosin University Medical Center from 1985 to 1993 to analyse the primary lesion, age and sex distributions, location of bone metastasis, patterns of metastasis according to the primary. The results were as follows : 1. The common origin of bone metastasis were lung(29.5%), stomach(15.3%), breast(11.3%), unknown(7.7%), cervix(5.3%), liver(4.8%) in order of frequency. 2. There were 251 men and 166 women and their mean age was 54.8 years and the peak age incidence was in 6th decades. Most cases(85.3%) were occured beyond 5th decades. 3. The preferred sites of metastatic deposits were spine(64.0%), pelvis(40.5%), rib(38.8%), femur(36.7%), skull(21.1%), humerus(13.9%), scapula(13.0%) in order of frequency. In the spine, thoracic(42.1%), lumbar(39.1%), cervical(13.2%), sacral(5.6%) vertebrae were involved in order of frequency. 4. Multiple bone metastases were more common(73.1%) than single metastasis(26.9%). 5. In the lung cancer, the peak age incidence was 6th decades, and the preferred sites of bone metastasis were spine, pelvis, femur. 6. In the stomach cancer, the peak age incidence was 6th decades, and the preferred sites of bone metastasis were spine, femur, pelvis. 7. In the breast cancer, the peak age incidence was 5th decades, and the preferred sites of bone metastasis were spine, rib, pelvis. 8. In the bone metastasis with unknown primary site, the peak age incidence was 7th decades, the preferred sites of bone metastasis were spine, femur, pelvis, and the common histologic types were adenocarcinoma and squamous cell carcinoma.

Prevalence and Survival Patterns of Patients with Bone Metastasis from Common Cancers in Thailand

Phanphaisarn, Areerak,Patumanond, Jayantorn,Settakorn, Jongkolnee,Chaiyawat, Parunya,Klangjorhor, Jeerawan,Pruksakorn, Dumnoensun Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.9

Background: Bone metastasis is a single condition but presents with various patterns and severities. Skeletal-related events (SREs) deteriorate overall performance status and reduce quality of life. However, guidelines for early detection and management are limited. This study includes a survey of the prevalence of bone metastasis in cases with common cancers in Thailand as well as a focus on survival patterns and SREs. Materials and Methods: A retrospective cohort analysis was conducted using a database of the Chiang Mai Cancer Registry and the Musculoskeletal Tumor Registry of the OLARN Center, Chiang Mai University. The prevalence of bone metastasis from each type of primary cancer was noted and time-to-event analysis was performed to estimate cancer survival rates after bone metastasis. Results: There were 29,447 cases of the ten most common cancers in Thailand, accounting for 82.2% of the entire cancer registry entries during the study period. Among those cases, there were 2,263 with bone metastases, accounting for 7.68% of entries. Bone metastasis from lung, liver, breast, cervix and prostate are common in the Thai population, accounting for 83.4% of all positive cases. The median survival time of all was 6 months. Of the bone metastases, 48.9% required therapeutic intervention, including treatment of spinal cord and nerve root compression, pathological fractures, and bone pain. Conclusions: The frequency of the top five types of bone metastasis in Thailand were different from the frequencies in other countries, but corresponded to the relative prevalence of the cancers in Thailand and osteophilic properties of each cancer. The results of this study support the establishment of country specific guidelines for primary cancer identification with skeletal lesions of unknown origin. In addition, further clinical studies of the top five bone metastases should be performed to develop guidelines for optimal patient management during palliative care.

악성종양에서 골수면역신티그라피를 이용한 골수전이의 평가 : $^{99m}Tc$-MDP 뼈스캔과의 비교

이경한,최창운,방영주,정준기,정홍근,이명철,김병국,김노경,고창순,Lee, Kyung-Han,Choi, Chang-Woon,Bang, Yung-Jue,Chung, Jun-Key,Chung, Hong-Keun,Lee, Myoung-Chul,Kim, Byoung-Kook,Kim, Noe-Kyeong,Koh, Chang-Soon 대한핵의학회 1994 핵의학 분자영상 Vol.28 No.1

Although bone scan is a highly sensitive test for detecting bone metastasis, its findings are often limited in specificity and cannot be used for assessing the bone marrow. Bone marrow scintigraphy may provide useful information but previous experience with radiolabelled colloid has been disappointing. Recently, $^{99m}Tc$ labeled anti-granulocyte monoclonal antibody (anti-NCA-95 MAb) has been introduced as a new bone marrow imaging agent. To evaluate the usefulness of $^{99m}Tc$ anti-NCA MAb bone marrow scans for detecting skeletal metastasis, bone marrow scans of 44 malignant tumor patients were evaluated and compared with bone scan findings. Bone scan showed abnormal lesions in 26(59%) cases, and 18 of these patients also had an abnormal bone marrow scan. Seven of the 8 patients who had normal bone marrow scan despite bone scan lesions were confirmed to be free from metastasis. There was one case with a marrow defect despite normal bone scan but the presence of metastasis was not determined due to loss of follow up. Bone scan demonstrated a total of 64 lesions while bone marrow scan showed 38 lesions. Fifty percent (32/64) of the bone scan lesions had matching marrow defects while the remaining 50% did not. Most of these non matched lesions were suggested to be nonspecific lesions such as rib fractures or degenerative change. Meanwhile bone marrow scan was able to detect 6 new lesions not detected by bone scan, bit metastasis in each lesion was not confirmed. Bone marrow scan was also helpful in assessing equivocal bone scan lesions to be of metastatic nature in 10 patients by demonstrating a matched marrow defect. Thus $^{99m}Tc$ anti-NCA MAb bone marrow scan can help exclude metastasis in patients with nonspecific bone scan lesions and may be able to detect metastatic lesions not seen with bone scan. It appears useful as a complementary study to bone scan in evaluating malignant tumor patients.

Targeting the Hepatocyte Growth Factor and c-Met Signaling Axis in Bone Metastases

Whang, Young Mi,Jung, Seung Pil,Kim, Meyoung-Kon,Chang, In Ho,Park, Serk In MDPI 2019 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.20 No.2

<P>Bone metastasis is the terminal stage disease of prostate, breast, renal, and lung cancers, and currently no therapeutic approach effectively cures or prevents its progression to bone metastasis. One of the hurdles to the development of new drugs for bone metastasis is the complexity and heterogeneity of the cellular components in the metastatic bone microenvironment. For example, bone cells, including osteoblasts, osteoclasts, and osteocytes, and the bone marrow cells of diverse hematopoietic lineages interact with each other via numerous cytokines and receptors. c-Met tyrosine kinase receptor and its sole ligand hepatocyte growth factor (HGF) are enriched in the bone microenvironment, and their expression correlates with the progression of bone metastasis. However, no drugs or antibodies targeting the c-Met/HGF signaling axis are currently available in bone metastatic patients. This significant discrepancy should be overcome by further investigation of the roles and regulation of c-Met and HGF in the metastatic bone microenvironment. This review paper summarizes the key findings of c-Met and HGF in the development of novel therapeutic approaches for bone metastasis.</P>

위암의 골 전이

김영환(Young Hwan Kim),채현석(Hiun Suk Chae),조영석(Young Seok Cho),이보인(Bo In Lee),김병욱(Byung Wook Kim),김성수(Sung Soo Kim),한석원(Sok Won Han),이창돈(Chang Don Lee),최규용(Kyu Yong Choi),차상복(Sang Bok Cha),정인식(In Sik Chun 대한내과학회 2002 대한내과학회지 Vol.63 No.3

목적 : 위암은 진단 내시경의 발달로 점차 조기 발견율이 높아지고 있다. 이에 따라 완치 목적의 수술적 치료를 받는 예가 늘고 있는데 따라서 수술 전 암의 전이 여부를 정확히 평가하는 것이 중요하다고 하겠다. 저자들은 위암에서 골 전이의 빈도를 추정해보고 이와 관련된 임상 인자들과의 상관관계를 조사하고자 하였다. 방법 : 1993년 1월 1일부터 2000년 12월 31일까지 가톨릭의대 부속 성모자애병원과 의정부성모병원에서 상부위장관내시경 검사상 육안 소견 및 조직 소견상 위암으로 진단된 226명의 환자들을 대상으로 하였다. 모든 환자에서 단순 흉부 X-선 촬영, 복부 전산화 단층촬영을 시행하여 병기 판정을 하였고 골 동위원소 검사 결과와 임상 양상, 단순 X-선 검사 결과를 참고하여 골 전이 여부를 추정하였다. 모든 대상 환자에서 위내시경 소견상 위암의 위치와 Borrmann 형태, 조직학적 형태에 따라 분류하여 골 전이와의 상관관계를 분석하였고, 간 전이나 폐 전이와의 동반 여부도 조사하였으며 혈액을 채취하여 칼슘, 인, alkaline phospatase, CEA, αFP 등을 측정하였다. 결과 : 226명의 대상 위암 환자 중 남자가 158명, 여자가 68명이며 조기 위암은 24.8%였다. 골 전이로 추정되는 환자의 빈도는 11.9%(56/226)이며 전이 장소는 척추가 가장 많았고 늑골, 두개골, 골반의 순이었다. 병기가 3기 이상, 원발 위암의 병소가 위 체부와 분문부인 경우에서 통계적으로 의의 있게 골 전이의 빈도가 높았고 조직학적 분류, 내시경상 암의 육안 형태, 간 전이 여부등과는 상관관계가 없었다. 혈액 검사 결과와의 비교에서는 CEA가 의의 있게 높았으며 칼슘, alkaline phosphatase는 골 전이 환자에서 증가하는 경향을 보였으나 통계적인 의의는 없었다. 결론 : 이상의 결과로 모든 위암 환자에서 병기 판정에 골 동위원소 검사를 시행하는 것은 비용면에서 효율적이지 못할 것이나 3기 이상의 진행성 위암 중 원발암의 병소 위치가 위 체부나 분문부이거나 CEA가 높은 경우 등에서는 골 전이에 대한 평가를 적극적으로 고려해야 할 것으로 생각된다. Background : It has been known that bone metastasis rarely occurs in gastric cancer, compared with lung and breast cancers. But its incidence is variable according to authors and has not been reported in Korea. We investigated the incidence and related clinical parameters of bone metastasis. Methods : We studied a total of 226 gastric cancer patients who were diagnosed by endoscopic biopsy at Our Lady of Mercy Hospital and UiJongBu St. Mary's Hospital from 1993 to 2000. We performed abdominal CT and bone scan at the time of cancer diagnosis in all patients. The data of parameters including gross findings on gastrofibroscopy, histology, laboratory findings were obtained for analysis. Results : 226 patients (male : 158 patients, female : 68 patients) were included and their mean age was 58.9±13.0 years. The rate of early gastric cancer was 24.8% and 75.2% for advanced cancer. The incidence of bone metastasis based on bone scintigram was 11.9% (27/226 subjects) and the main involvement sites were spine (81.5%), rib (74.1%), skull (29.6%), pelvis (14.8%). The incidence was higher in advanced stage or corpus location or elevated CEA level. Other parameters including age, sex, pathology, endoscopic gross morphology, levels of Ca, alkaline phosphatase were not significant in relation to bone metastasis. Bone metastasis was more related to lung metastasis than liver metastasis. Conclusion : In our study, bone metastasis is not rare in gastric cancer. Therefore, the evaluation of it should be performed selectively according to the staging, tumor location and tumor marker level.(Korean J Med 63:322-328, 2002)

구강 편평상피세포암의 골전이 모델

박영욱,오유진,이희수,Park, Young-Wook,Oh, Yu-Jin,Lee, Hee-Su 대한악안면성형재건외과학회 2010 Maxillofacial Plastic Reconstructive Surgery Vol.32 No.2

Background and Purpose: Bone metastases rarely occur in patients with oral squamous cell carcinoma (OSCC), so the molecular mechanisms of bone metastasis of OSCC remains unclear. Studies with animal models allow progresses in understanding the molecular events for bone metastasis and provide new targets for therapy. So we tried to establish a murine model for bone metastasis of oral squamous cell carcinoma. Materials and Methods: Human OSCC cells (KB cell line) were xenografted to nude mice via direct inoculation into the tibial marrow. Mice with tibial tumors were sacrificed once a week, until seven weeks after the injection of human tumor cells. Growth of tibial tumors were observed by histology. Expression of TGF-$\beta$ and CXCR-4 in bone OSCC (experimental) and subcutaneous tumor (control) was also evaluated by immunohistochemical staining. Results: Bone OSCC was successfully induced by intra-tibial injection of KB cells. Tumor mass was developed in the marrow tissues of tibia and finally invade the endosteum of tibia. Immunohistochemical staining showed higher expression of TGF-$\beta$ in bone tumors than in subcutaneous tumors. Conclusion: A murine model of bone metastasis of OSCC was suggested that imitated the clinical findings of distant vascular metastasis. This bone tumor model should facilitate understanding of the molecular pathogenesis of OSCC bone metastasis, and aid in the developement of treatment strategies against OSCC bone metastasis.

A Prognostic Model to Predict Clinical Outcome in Gastric Cancer Patients with Bone Metastasis

Park, Hyung Soon,Rha, Sun Young,Kim, Hyo Song,Hyung, Woo Jin,Park, Ji Soo,Chung, Hyun Cheol,Noh, Sung Hoon,Jeung, Hei-Cheul S. Karger AG 2011 Oncology Vol.80 No.1

<P>Abstract</P><P><I>Background:</I> The clinicopathological manifestations and treatment outcomes of bone metastasis of gastric cancer are largely unknown. We delineated a prognostic model to identify different risk groups on the basis of clinical parameters. <I>Methods:</I> Patients who had bone metastasis at the time of diagnosis of gastric cancer (synchronous metastasis) or who developed bone metastasis during follow-up (metachronous metastasis) were retrospectively reviewed from January 1998 to May 2008. <I>Results:</I> Bone metastasis was identified in 203 (2.4%) of 8,633 patients: 126 patients (62%) with synchronous metastasis and 77 patients with metachronous metastasis. The median time to event was 16 months (range 4–87). As for treatment, 120 patients (59%) received systemic chemotherapy. The median survival time was 103 days (95% CI 80–126). Poor performance status [Eastern Cooperative Oncology Group 3–4; relative risk (RR) = 1.91, p = 0.011], multiple bone metastasis (RR = 2.593, p = 0.002), and abnormal carcinoembryonic antigen (RR = 1.779, p = 0.004) implied independent factors for survival. For patients who had zero to two of these factors identified, chemotherapy had a beneficial effect (175 vs. 43 days; p < 0.0001). <I>Conclusion:</I> We recommend that the therapeutic approach with bone metastasis be customized to facilitate the risk stratification, so as to consequently provide the most appropriate therapy for each patient.</P><P>Copyright © 2011 S. Karger AG, Basel</P>