Is the isolated bone change in advanced colorectal cancer a necessarily malignant metastasis? A case series

Is the isolated bone change in advanced colorectal cancer a necessarily malignant metastasis? A case series | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Is the isolated bone change in advanced colorectal cancer a necessarily malignant metastasis? A case series Xin Sun, Xiaomei Yang, Wenjuan Chen, Juan Chen, Xiujuan Qu, Jinglei Qu, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4196745/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Radiation osteitis (RO) is one of the bone complications arising after radiotherapy (RT). Limited to atypical manifestation in imaging. RO is difficult to diagnose, and sometimes, it could be considered as an early bone metastasis (BM), resulting in improper treatment. Thus, it’s vital to provide reliable evidence to clarify the isolated bone changes. Herein, we reported two advanced colorectal cancer (CRC) patients with atypical, isolated bone change in imaging, and both had underwent postoperative chemotherapy and radiotherapy. After medical imaging and clinical laboratory tests, the isolated bone change was finally confirmed to be RO rather than BM. The case series presented precision assessment for differentiating RO from BM, which may change the treatment strategy of this subgroup of patients. Keywords: Radiation osteitis, radiotherapy, pelvis, diagnosis, bone metastasis. Radiation osteitis radiotherapy pelvis diagnosis bone metastasis Figures Figure 1 Figure 2 Figure 3 Introduction Bone metastasis is one of the most serious bone complications in malignant solid tumors. The incidence of BM is about 10% to 15% in advanced CRC ( Jeong, S. et al. 2005, Sundermeyer, M. et al. 2005) . Nowadays, BM is mainly diagnosed by biochemical-markers and bone imaging techniques, such as emission computed tomography (ECT), nuclear magnetic resonance (MR), positron emission tomography (PET), and computed tomography (CT) (Zhonghua Zhong et al. 2020, O'Sullivan, G.J. et al. 2015, Huang, Q. et al. 2012) . However, due to the lack of typical manifestation, the methods are not sensitive or specific enough for detection of early BM. Radiation osteitis (RO) is often considered as the early stage of radiation-induced response after radiotherapy, which might develop into osteoradionecrosis or fractures. Risk factors include the age and health status of the patient, absorbed dose, radiation field, beam energy and fractionation , etc. ( Mitchell, M. et al. 1998, Kim J. et al. 1974) It’s an inflammatory response with bone marrow oedema pattern, without morphological evidence of necrosis in punctuated or confluent hyperintensities on T1wi+ contrast and turbo-inversion recovery magnitude sequences (Meixel, et al. 2018). In pelvic radiotherapy, RO of sacral bone is the most common manifestation due to the amount of red bone marrow within the central field of pelvic radiation [8]. Yet, there is little evidence for the diagnosis of RO in the pelvis and it is easily misdiagnosed as BM, leading to unfavorable outcomes. Herein, we firstly reported two advanced CRC patients with isolated bone change, finally confirmed as RO rather than BM; we have also presented a review of the diagnosis and the potential differential diagnosis. Case presentation Case 1: A 57-year-old female without medical or family history of cancer presented to the hospital with diarrhea in March 2020. Colonoscopy revealed an ulcerative mass in sigmoid colon. Postoperative pathology demonstrated moderately differentiated tubular adenocarcinoma, and the pathological staging was pT4bN0M0 according to AJCC Version 8.0. Immunohistochemistry (IHC) presented microsatellite stability (MSS), and gene test noted somatic mutations of KRAS- p.G12V. Two cycles of XELOX (Xeloda/Oxaliplatin) regimes were performed after surgery. The CT and PET/CT in September 2020 suggested no recurrence or metastasis. Then, the patient underwent radiotherapy since September 2020, with a total dose of 50.4 Gray (Gy) in 28 frictions, without simultaneous chemotherapy because of myelosuppression. The treatment field is shown in Fig.1 (A-C). After radiotherapy, the patient took five cycles of Xeloda until May 2021. On January 5th, 2022, the enhanced CT revealed a metastatic node in the peritoneal cavity. Disease-free survival (DFS) was 20 months. PET/CT implied the maximum standardized uptake value (SUVmax) of the node was 14.6. There was also abnormality in bone: PET/CT indicated that the SUVmax of sacral bone was 3.3 (Fig.2); the enhanced magnetic resonance image (MRI) of pelvic cavity revealed low-intensity images on T1-weighted imaging and high-intensity images on T2-weighted imaging in bilateral sacrum and left ilium. Gd-DTPA-enhanced T1-weighted MRI showed inhomogeneous enhancement of the bilateral sacroiliac joint; the bilateral sacroiliac joint space was blurred, and no obvious swelling of surrounding soft tissue. Moreover, the alkaline phosphatase (ALP) was 107 U/L. The patient had no bone-related symptoms. The diagnosis of bone metastases in this patient was not excluded. During January to June 2022, the patient received XELIRI (Xeloda/Irinotecan) and bevacizumab for one cycle; because of Grade-3 vomiting and Grade-4 myelosuppression, the treatment was adjusted to XELOX and bevacizumab for another five cycles. Zoledronic acid was used over six cycles at the same time. During the treatment, the metastatic node shrunk with SUVmax of 10.6, while the SUVmax of the sacrum was 2.8 with no other improvement. MRI demonstrated that there’s no obvious change compared to the previous time: ALP remained normal (82 U/L). We considered whether the patient had access to surgery or radiotherapy for the metastatic node in peritoneal cavity. Multi-disciplinary treatment (MDT) considered it should be diagnosed as radiation-induced osteonecrosis rather than bone metastasis. Case 2: A 64-year-old female presented with bloody stool in December 2020. Colonoscopy revealed a rectal mass. Sugary was performed. Postoperative pathology indicated moderately differentiated and partially ulcerative tubular adenocarcinoma, and pathological staging was pT4bN0M0. IHC suggested MSS, and the gene test revealed somatic mutations of KRAS. Two cycles of XELOX regime were performed after surgery. The patient underwent radiotherapy from June to July 2021, and the dose administered was 50.4 Gy in 28 fractions, with oral administration of Xeloda at the same time. The treatment field is shown in Fig.1(D-F). After radiotherapy, three cycles of XELOX were performed until September 2021. A left adnexial mass was found in March 2022, PET/CT showed the SUVmax was 10.9, and carcinoembryonic antigen (CEA) increased to 25.16 ng/ml, ALP was 95 U/L. The DFS was 12 months. Eight cycles of chemotherapy were performed, which involved irinotecan and retitraxel, from March to September 2022, during which the CEA reduced to 9.42 ng/ml and the left adnexial mass shrunk, with SUVmax of 3.7. At this time, the patient would have the opportunity for surgery. However, in routine preoperative examinations, PET/CT indicated that the SUVmax in the left sacral was 4.6, and the bone (as evinced by CT) was changed during treatment (Fig.3). MRI showed low-intensity images on T1-weighted imaging and high-intensity images on T2-weighted imaging in sacrum and bilateral iliac bone. ALP was 95 U/L. The patient was asymptomatic. MDT considered the focus in bone should be diagnosed as radiation-induced osteonecrosis rather than BM. Then the patient was subject to resection of the metastatic node in the left side and remained alive. The summary of the characteristics and treatments of the two cases is shown in Table 1. Discussion Compared with RO, BM usually means a case far from no evidence of disease (NED) and is associated poor survival. Thus, identifying BM and RO correctly is vital for advanced CRC patients. Pathology remains the gold-standard for diagnosing BM, however, it is invasive. Imaging is the most widely used method for diagnosing BM ( O'Sullivan et al.2015). MRI is acknowledged for diagnosing BM, especially for early BM. BM often character as discrete foci of low T1-signals because of the replacement of normal fatty marrow by malignant cells; on a T2-weighted sequence, BM usually present T2 hyperintensity due to the elevated water content and gadolinium enhancement due to increased vascularity associated therewith ( O'Sullivan et al.2015). Biochemical-markers contribute to diagnosis of BM usually include tumor biomarkers, ALP, N- and C-terminal propeptide of procollagen type I (PINP and PICP), tartrate-resistant acid phosphatase isoform, bone sialoprotein, etc. [(Huang, Q.et al, 2012). A history of pelvic irradiation is important for diagnosing RO. Besides, RO is featured by mottled areas of bone, with osteopenia, coarse trabeculation, and areas of focally increased bone density. The changes usually start at the iliac side of the sacroiliac joint and process to involve the entire joint (Bluemke et al., 2019). Blastic, or mixed blastic and lytic, lesions in the field of radiotherapy without associated masses usually suggest RO in CT (Yousem et al., 1989) . Yoshioka et al. found MRI signal patterns in RO are of low signal intensity (in T1-weighted images), mixed signal intensity around sacroiliac joints, and high signal intensity in the peripheral areas (in T2-weighted images), indicating edematous changes, and gadolinium enhancement may be seen due to fibrotic changes (Yoshioka et al., 2000). Meixel et al. defined a RISC (Radiation-Induced Sacral Change) classification according to MRI, in which RO showed iso-/hypointense responses in T1wi, hyperintense responses in T2wi, hyperintense (punctuated or confluent) responses in T1wi +contrast, and hyperintense response in turbo-inversion recovery magnitude (Meixel et al., 2018). These case series provide experience for differentiating RO from BM correctly in advanced CRC patients. There’s no study with a focus on this condition at the time of writing. In our cases, we found that the age of both patients was around 60 years, and the time-to-onset of RO was about one year after radiotherapy with the dose exceeding 50 Gy. The main regions of bone changes were the sacrum and ilium. These were consistent with previous studies which focused on RO ( Meixel et al., 2018, Yoshioka et al., 2014) . Increased CEA was not sufficiently valuable to indicate changes in bone because of the solitary metastasis of other part, and we found the ALP was normal during treatment. Radiology, especially MRI, was considered as the best technique to diagnose RO. In Case 1, PET/CT showed the abnormal uptake of sacrum, which usually implies bone metastasis. Although manifestations in MRI/CT implied that the bone changes were unilateral with cortical destruction therein, but there were no significant changes after anti-tumor therapy and anti-osteoporosis. We finally diagnosed the patient as solitary metastasis of peritoneal cavity with RO. In Case 2, during the anti-tumor treatment, PET/CT exhibited the abnormal uptake of sacrum. This was confused when trying to confirm the bone change was BM or some other cause. However, the bone changes in MRI/CT showed bilateral and complete cortical bone. The patient was considered as solitary metastasis of the left accessory area with RO and underwent a surgery to remove the solitary metastasis in October 2022. The strength of the case series is such that we provide complete and novel imaging related to RO, which is vital for the radiologist to understand the imaging characteristics, location, and morphology of RO better. The limitation of the present research is that the lesions were not biopsied because of the age of the patient and risk of complications. However, MDT discussion was undertaken, which was acknowledged as being important for patients in that it avoided unnecessary biopsy. In conclusion, our cases indicated that isolated bone change in advanced CRC patients may be RO rather than BM, so the patients could receive different treatments. However, more specific standards for differential diagnosis are warranted. Abbreviations radiation osteitis: RO radiotherapy: RT bone metastasis: BM colorectal cancer: CRC microsatellite stability: MSS computed tomography: CT positron emission tomography-CT: PET/CT maximum standardized uptake value: SUVmax magnetic resonance image: MRI alkaline phosphatase: ALP Multi-disciplinary treatment: MDT Declarations Funding: The present study was supported by High-level innovation and entrepreneurship team of Liaoning Province’s “Xing Liao Talents Program” (XLYC2008006)；“China Medical University-Chinese Academy of Sciences Shenyang Branch Scientist Partner” project (HZHB2022002) Conflict of interest: The authors have no conflicts of interest relevant to this article. Data Availability Statement: Available upon request to the corresponding author. Author Contributions: Xin Sun made substantial contributions to the conception and design of the work and contributed to collecting the data and drafting the manuscript. Xiaomei Yang contributed to collecting the data and drafting the manuscript. Wenjuan Chen and Juan Chen contributed to collecting the data; Xiujuan Qu helped design the manuscript; Ying Chen and Jinglei Qu helped design and revise the manuscript. Ethics approval: Not appliable. Consent to participate: Informed consent was obtained from all individual participants included in the study. Consent to publication: A written informed consent for publication was obtained. References Jeong, S., et al., Re: Colon cancer survival rates with the new American Joint Committee on Cancer sixth edition staging. 2005. 97(22): p. 1705-6; author reply 1706-7. DOI: 10.1093/jnci/dji383 Sundermeyer, M., et al., Changing patterns of bone and brain metastases in patients with colorectal cancer. 2005. 5(2): p. 108-13. DOI: 10.3816/ccc.2005.n.022 [Chinese expert consensus on multidisciplinary treatment of bone metastasis from colorectal cancer (2020 version)]. Zhonghua Zhong Liu Za Zhi, 2020. 42(6): p. 433-437. DOI: 10.3760/cma.j.cn112152-20200402-00295 O'Sullivan, G.J., F.L. Carty, and C.G. Cronin, Imaging of bone metastasis: An update. World J Radiol, 2015. 7(8): p. 202-11. DOI: 10.4329/wjr.v7.i8.202 Huang, Q. and X. Ouyang, Biochemical-markers for the diagnosis of bone metastasis: a clinical review. Cancer Epidemiol, 2012. 36(1): p. 94-8. DOI: 10.1016/j.canep.2011.02.001 Mitchell, M. and P.J.R.a.r.p.o.t.R.S.o.N.A. Logan, Inc, Radiation-induced changes in bone. 1998. 18(5): p. 1125-36; quiz 1242-3. DOI: 10.1148/radiographics.18.5.9747611 Kim, J., et al., Proceedings: Time dose factors in radiation induced osteitis. 1974. 120(3): p. 684-90. DOI: 10.2214/ajr.120.3.684 Meixel, A.J., et al., From radiation osteitis to osteoradionecrosis: incidence and MR morphology of radiation-induced sacral pathologies following pelvic radiotherapy. Eur Radiol, 2018. 28(8): p. 3550-3559. DOI: 10.1007/s00330-018-5325-2 Bluemke, D., E. Fishman, and W.J.R.a.r.p.o.t.R.S.o.N.A. Scott, Inc, Skeletal complications of radiation therapy. 1994. 14(1): p. 111-21. DOI: 10.1148/radiographics.14.1.8128043 Yousem, D.M., et al., Treated invasive cervical carcinoma. Utility of computed tomography in distinguishing between skeletal metastases and radiation necrosis. Clin Imaging, 1989. 13(2): p. 147-53. DOI: 10.1016/0899-7071(89)90098-3 Yoshioka, H., et al., MR imaging of radiation osteitis in the sacroiliac joints. 2000. 18(2): p. 125-8. DOI: 10.1016/s0730-725x(99)00129-0 Ugurluer, G., et al., Bone complications after pelvic radiation therapy: evaluation with MRI. J Med Imaging Radiat Oncol, 2014. 58(3): p. 334-40. DOI: 10.1111/1754-9485.12176 Table Table 1: Summary of the characteristics and treatments of the two cases patients 1 2 Age 57 64 Sex female female Race Asian Asian Site of the cancer sigmoid rectum Staging after surgery pT4bN0M0 pT4bN0M0 Radiotherapy 50.4 Gy in28 frictions 50.4 Gy in28 frictions Site of metastasis peritoneal cavity left side Site of RO Sacrum, ilium Sacrum, ilium MMR protein analysis MSS MSS Gene test somatic mutations of KRAS, FGFR and PIK3CA somatic mutations of KRAS Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4196745","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":285986020,"identity":"62955db6-f1cc-4163-b5de-26f0ca32387d","order_by":0,"name":"Xin Sun","email":"","orcid":"","institution":"Department of Medical Oncology, The First Hospital of China Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xin","middleName":"","lastName":"Sun","suffix":""},{"id":285986021,"identity":"090973b2-08fb-45c1-a9f9-9def290d7acd","order_by":1,"name":"Xiaomei Yang","email":"","orcid":"","institution":"Department of Medical Oncology, The First Hospital of China Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xiaomei","middleName":"","lastName":"Yang","suffix":""},{"id":285986022,"identity":"622d5bf5-c7fd-4bb9-8327-7a47fc4333c5","order_by":2,"name":"Wenjuan Chen","email":"","orcid":"","institution":"Department of Medical Oncology, The First Hospital of China Medical University","correspondingAuthor":false,"prefix":"","firstName":"Wenjuan","middleName":"","lastName":"Chen","suffix":""},{"id":285986023,"identity":"193bccf7-b0b2-4559-baec-a058a030e767","order_by":3,"name":"Juan Chen","email":"","orcid":"","institution":"Department of Medical Oncology, The First Hospital of China Medical University","correspondingAuthor":false,"prefix":"","firstName":"Juan","middleName":"","lastName":"Chen","suffix":""},{"id":285986024,"identity":"9edeb651-aba0-4c90-ac46-7236d1e6d014","order_by":4,"name":"Xiujuan Qu","email":"","orcid":"","institution":"Department of Medical Oncology, The First Hospital of China Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xiujuan","middleName":"","lastName":"Qu","suffix":""},{"id":285986025,"identity":"0cf782f4-d191-48f6-ae82-4a84bbe19561","order_by":5,"name":"Jinglei Qu","email":"","orcid":"","institution":"Department of Medical Oncology, The First Hospital of China Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jinglei","middleName":"","lastName":"Qu","suffix":""},{"id":285986026,"identity":"edf8b77c-e715-460e-a246-09eeac880da4","order_by":6,"name":"Ying Chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/ElEQVRIiWNgGAWjYDCCAxAqAcq24eFnbyBNS5qMZM8BErQAwWEbgxsO+HXwHe89/Jqnwi6PX7rH8HDBr/M8DDcYGD98zMGtRfLMuTRrnjPJxZJzzhgcntl3m4dxdgOz5MxtuLUY3MgxM+ZtO5C44UaOwWHents8zDIH2Jh5CWr5dyBxP0TLOR42iQSCWowf8zYAbZEAauH5cYCHh5AWyTNnzBjnHEtOnHEjreAwb0MyjwTPwWa8fuE73mP84U2NXWL/jOTNn3n+2NnbH28++OEjHi1AwCbFA6Y5DBgY20AMxga86oGA+eMPMM3+gIHhDyHFo2AUjIJRMBIBABStW2reSalcAAAAAElFTkSuQmCC","orcid":"","institution":"Department of Medical Oncology, The First Hospital of China Medical University","correspondingAuthor":true,"prefix":"","firstName":"Ying","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2024-03-31 18:00:51","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4196745/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4196745/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":54116401,"identity":"285a41e1-f39c-4f14-9ced-9995ea4a4598","added_by":"auto","created_at":"2024-04-04 19:45:24","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":315883,"visible":true,"origin":"","legend":"\u003cp\u003eRegion of radiotherapy\u003c/p\u003e\n\u003cp\u003eA-C: Region of radiotherapy of case 1\u003c/p\u003e\n\u003cp\u003eD-F: Region of radiotherapy of case 2\u003c/p\u003e","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4196745/v1/5915045daedc8e3ed228a517.jpg"},{"id":54116404,"identity":"957eb744-4589-483f-978e-acfac884a977","added_by":"auto","created_at":"2024-04-04 19:45:24","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":7518931,"visible":true,"origin":"","legend":"\u003cp\u003eBone changes of the patient in case 1\u003c/p\u003e\n\u003cp\u003eA：The bone change in 2022.1 and 2022.6 by CT\u003c/p\u003e\n\u003cp\u003eB：The bone change in 2022.1 and 2022.6 by PET-CT.\u003c/p\u003e\n\u003cp\u003eC: The bone change in 2022.1 and 2022.6 by MRI\u003c/p\u003e\n\u003cp\u003eThe red circle presented the bone change\u003c/p\u003e\n\u003cp\u003eThe red arrow presented the solitary metastatic node in the peritoneal cavity\u003c/p\u003e","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4196745/v1/bcf5c4ff01a4be4c74539a7e.jpg"},{"id":54116402,"identity":"5376cd4a-1d0e-419e-ba2d-1ad28a2f7528","added_by":"auto","created_at":"2024-04-04 19:45:24","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":2029377,"visible":true,"origin":"","legend":"\u003cp\u003eBone changes of the patient in case 2\u003c/p\u003e\n\u003cp\u003eA-C: The bone change showed by CT in 2022.3, 2022.6 and 2022.8\u003c/p\u003e\n\u003cp\u003eD: The bone change in 2022.3 showed by PET-CT.\u003c/p\u003e\n\u003cp\u003eE-F: The bone change showed by PET-CT and MRI in 2022.9.\u003c/p\u003e\n\u003cp\u003eThe red circle presented the bone change\u003c/p\u003e\n\u003cp\u003eThe red arrow presented the solitary metastatic node in left region.\u003c/p\u003e","description":"","filename":"Fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4196745/v1/5ade4e7c74d84d526b360dcc.jpg"},{"id":54166927,"identity":"b007e83f-e75f-4cb9-87c3-5689fb1fad9d","added_by":"auto","created_at":"2024-04-05 13:36:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":562149,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4196745/v1/9d05a918-a3d0-49a9-af30-29f9a85c3a07.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Is the isolated bone change in advanced colorectal cancer a necessarily malignant metastasis? A case series","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBone metastasis is one of the most serious bone complications in malignant solid tumors. The incidence of BM is about 10% to 15% in advanced CRC\u0026nbsp;(\u0026nbsp;Jeong, S. et al. 2005,\u0026nbsp;Sundermeyer, M. et al. 2005)\u0026nbsp;. Nowadays, BM is mainly diagnosed by biochemical-markers and bone imaging techniques, such as emission computed tomography (ECT), nuclear magnetic resonance (MR), positron emission tomography (PET), and computed tomography (CT)\u0026nbsp;(Zhonghua Zhong\u0026nbsp;et al. 2020,\u0026nbsp;O\u0026apos;Sullivan, G.J. et al. 2015,\u0026nbsp;Huang, Q. et al. 2012)\u0026nbsp;. However, due to the lack of typical manifestation, the methods are not sensitive or specific enough for detection of early BM.\u003c/p\u003e\n\u003cp\u003eRadiation osteitis (RO) is often considered as the early stage of radiation-induced response after radiotherapy, which might develop into osteoradionecrosis or fractures. Risk factors include the age and health status of the patient, absorbed dose, radiation field, beam energy and fractionation\u0026nbsp;, etc.\u0026nbsp;(\u0026nbsp;Mitchell, M.\u0026nbsp;et al. 1998,\u0026nbsp;Kim J. et al. 1974) It\u0026rsquo;s an inflammatory response with bone marrow oedema pattern, without morphological evidence of necrosis in punctuated or confluent hyperintensities on T1wi+ contrast and turbo-inversion recovery magnitude sequences\u0026nbsp;(Meixel, et al. 2018). In pelvic radiotherapy, RO of sacral bone is the most common manifestation due to the amount of red bone marrow within the central field of pelvic radiation\u0026nbsp;[8]. Yet, there is little evidence for the diagnosis of RO in the pelvis and it is easily misdiagnosed as BM, leading to unfavorable outcomes.\u003c/p\u003e\n\u003cp\u003eHerein, we firstly reported two advanced CRC patients with isolated bone change, finally confirmed as RO rather than BM; we have also presented a review of the diagnosis and the potential differential diagnosis.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eCase 1: A 57-year-old female without medical or family history of cancer presented to the hospital with diarrhea in March 2020. Colonoscopy revealed an ulcerative mass in sigmoid colon. Postoperative pathology demonstrated moderately differentiated tubular adenocarcinoma, and the pathological staging was pT4bN0M0 according to AJCC Version 8.0. Immunohistochemistry (IHC) presented microsatellite stability (MSS), and gene test noted somatic mutations of KRAS- p.G12V. Two cycles of XELOX (Xeloda/Oxaliplatin) regimes were performed after surgery. The CT and PET/CT in September 2020 suggested no recurrence or metastasis. Then, the patient underwent radiotherapy since September 2020, with a total dose of 50.4 Gray (Gy) in 28 frictions, without simultaneous chemotherapy because of myelosuppression. The treatment field is shown in Fig.1 (A-C). After radiotherapy, the patient took five cycles of Xeloda until May 2021. On January 5th, 2022, the enhanced CT revealed a metastatic node in the peritoneal cavity. Disease-free survival (DFS) was 20 months. PET/CT implied the maximum standardized uptake value (SUVmax) of the node was 14.6. There was also abnormality in bone: PET/CT indicated that the SUVmax of sacral bone was 3.3 (Fig.2); the enhanced magnetic resonance image (MRI) of pelvic cavity revealed low-intensity images on T1-weighted imaging and high-intensity images on T2-weighted imaging in bilateral sacrum and left ilium. Gd-DTPA-enhanced T1-weighted MRI showed inhomogeneous enhancement of the bilateral sacroiliac joint; the bilateral sacroiliac joint space was blurred, and no obvious swelling of surrounding soft tissue. Moreover, the alkaline phosphatase (ALP) was 107 U/L. The patient had no bone-related symptoms. The diagnosis of bone metastases in this patient was not excluded. During January to June 2022, the patient received XELIRI (Xeloda/Irinotecan) and bevacizumab for one cycle; because of Grade-3 vomiting and Grade-4 myelosuppression, the treatment was adjusted to XELOX and bevacizumab for another five cycles. Zoledronic acid was used over six cycles at the same time. During the treatment, the metastatic node shrunk with SUVmax of 10.6, while the SUVmax of the sacrum was 2.8 with no other improvement. MRI demonstrated that there’s no obvious change compared to the previous time: ALP remained normal (82 U/L). We considered whether the patient had access to surgery or radiotherapy for the metastatic node in peritoneal cavity. Multi-disciplinary treatment (MDT) considered it should be diagnosed as radiation-induced osteonecrosis rather than bone metastasis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCase 2: A 64-year-old female presented with bloody stool in December 2020. Colonoscopy revealed a rectal mass. Sugary was performed. Postoperative pathology indicated moderately differentiated and partially ulcerative tubular adenocarcinoma, and pathological staging was pT4bN0M0. IHC suggested MSS, and the gene test revealed somatic mutations of KRAS. Two cycles of XELOX regime were performed after surgery. The patient underwent radiotherapy from June to July 2021, and the dose administered was 50.4 Gy in 28 fractions, with oral administration of Xeloda at the same time. The treatment field is shown in Fig.1(D-F). After radiotherapy, three cycles of XELOX were performed until September 2021. A left adnexial mass was found in March 2022, PET/CT showed the SUVmax was 10.9, and carcinoembryonic antigen (CEA) increased to 25.16 ng/ml, ALP was 95 U/L. The DFS was 12 months. Eight cycles of chemotherapy were performed, which involved irinotecan\u0026nbsp;and\u0026nbsp;retitraxel, from March to September 2022, during which the CEA reduced to 9.42 ng/ml and the left adnexial mass shrunk, with SUVmax of 3.7. At this time, the patient would have the opportunity for surgery. However, in routine preoperative examinations, PET/CT indicated that the SUVmax in the left sacral was 4.6, and the bone (as evinced by CT) was changed during treatment (Fig.3). MRI showed low-intensity images on T1-weighted imaging and high-intensity images on T2-weighted imaging in sacrum and bilateral iliac bone. ALP was 95 U/L. The patient was asymptomatic. MDT considered the focus in bone should be diagnosed as radiation-induced osteonecrosis rather than BM. Then the patient was subject to resection of the metastatic node in the left side and remained alive.\u003c/p\u003e\n\u003cp\u003eThe summary of the characteristics and treatments of the two cases is shown in Table 1.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eCompared with RO, BM usually means a case far from no evidence of disease (NED) and is associated poor survival. Thus, identifying BM and RO correctly is vital for advanced CRC patients. Pathology remains the gold-standard for diagnosing BM, however, it is invasive. Imaging is the most widely used method for diagnosing BM\u0026nbsp;(\u0026nbsp;O\u0026apos;Sullivan\u0026nbsp;et al.2015). MRI is acknowledged for diagnosing BM, especially for early BM. BM often character as discrete foci of low T1-signals because of the replacement of normal fatty marrow by malignant cells; on a T2-weighted sequence, BM usually present T2 hyperintensity due to the elevated water content and gadolinium enhancement due to increased vascularity associated therewith\u0026nbsp;(\u0026nbsp;O\u0026apos;Sullivan\u0026nbsp;et al.2015).\u0026nbsp;Biochemical-markers contribute to diagnosis of BM usually include tumor biomarkers, ALP, N- and C-terminal propeptide of procollagen type I (PINP and PICP), tartrate-resistant acid phosphatase isoform, bone sialoprotein, etc.\u0026nbsp;[(Huang, Q.et al, 2012).\u003c/p\u003e\n\u003cp\u003eA history of pelvic irradiation is important for diagnosing RO. Besides, RO is featured by mottled areas of bone, with osteopenia, coarse trabeculation, and areas of focally increased bone density. The changes usually start at the iliac side of the sacroiliac joint and process to involve the entire joint\u0026nbsp;(Bluemke et al., 2019). Blastic, or mixed blastic and lytic, lesions in the field of radiotherapy without associated masses usually suggest RO in CT\u0026nbsp;(Yousem et al., 1989)\u0026nbsp;. Yoshioka et al. found MRI signal patterns in RO are of low signal intensity (in T1-weighted images), mixed signal intensity around sacroiliac joints, and high signal intensity in the peripheral areas (in T2-weighted images), indicating edematous changes, and gadolinium enhancement may be seen due to fibrotic changes\u0026nbsp;(Yoshioka et al.,\u0026nbsp;2000). Meixel et al. defined a RISC (Radiation-Induced Sacral Change) classification according to MRI, in which RO showed iso-/hypointense responses in T1wi, hyperintense responses in T2wi, hyperintense (punctuated or confluent) responses in T1wi +contrast, and hyperintense response in turbo-inversion recovery magnitude\u0026nbsp;(Meixel et al., 2018).\u003c/p\u003e\n\u003cp\u003eThese case series provide experience for differentiating RO from BM correctly in advanced CRC patients. There\u0026rsquo;s no study with a focus on this condition at the time of writing. In our cases, we found that the age of both patients was around 60 years, and the time-to-onset of RO was about one year after radiotherapy with the dose exceeding 50 Gy. The main regions of bone changes were the sacrum and ilium. These were consistent with previous studies which focused on RO\u0026nbsp;(\u0026nbsp;Meixel et al., 2018,\u0026nbsp;Yoshioka et al., 2014)\u0026nbsp;. Increased CEA was not sufficiently valuable to indicate changes in bone because of the solitary metastasis of other part, and we found the ALP was normal during treatment. Radiology, especially MRI, was considered as the best technique to diagnose RO. In Case 1, PET/CT showed the abnormal uptake of sacrum, which usually implies bone metastasis. Although manifestations in MRI/CT implied that the bone changes were unilateral with cortical destruction therein, but there were no significant changes after anti-tumor therapy and anti-osteoporosis. We finally diagnosed the patient as solitary metastasis of peritoneal cavity with RO. In Case 2, during the anti-tumor treatment, PET/CT exhibited the abnormal uptake of sacrum. This was confused when trying to confirm the bone change was BM or some other cause. However, the bone changes in MRI/CT showed bilateral and complete cortical bone. The patient was considered as solitary metastasis of the left accessory area with RO and underwent a surgery to remove the solitary metastasis in October 2022.\u003c/p\u003e\n\u003cp\u003eThe strength of the case series is such that we provide complete and novel imaging related to RO, which is vital for the radiologist to understand the imaging characteristics, location, and morphology of RO better. The limitation of the present research is that the lesions were not biopsied because of the age of the patient and risk of complications. However, MDT discussion was undertaken, which was acknowledged as being important for patients in that it avoided unnecessary biopsy.\u003c/p\u003e\n\u003cp\u003eIn conclusion, our cases indicated that isolated bone change in advanced CRC patients may be RO rather than BM, so the patients could receive different treatments. However, more specific standards for differential diagnosis are warranted.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eradiation osteitis: RO\u003c/p\u003e\n\u003cp\u003eradiotherapy: RT\u003c/p\u003e\n\u003cp\u003ebone metastasis: BM\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ecolorectal cancer: CRC\u003c/p\u003e\n\u003cp\u003emicrosatellite stability: MSS\u003c/p\u003e\n\u003cp\u003ecomputed tomography: CT\u003c/p\u003e\n\u003cp\u003epositron emission tomography-CT: PET/CT\u003c/p\u003e\n\u003cp\u003emaximum standardized uptake value: SUVmax\u003c/p\u003e\n\u003cp\u003emagnetic resonance image: MRI\u003c/p\u003e\n\u003cp\u003ealkaline phosphatase: ALP\u003c/p\u003e\n\u003cp\u003eMulti-disciplinary treatment: MDT\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eFunding:\u0026nbsp;The present study was supported by High-level innovation and entrepreneurship team of Liaoning Province’s “Xing Liao Talents Program” (XLYC2008006)；“China Medical University-Chinese Academy of Sciences Shenyang Branch Scientist Partner” project (HZHB2022002)\u003c/p\u003e\n\u003cp\u003eConflict of interest:\u0026nbsp;The authors have no conflicts of interest relevant to this article.\u003c/p\u003e\n\u003cp\u003eData Availability Statement: Available upon request to the corresponding author.\u003c/p\u003e\n\u003cp\u003eAuthor Contributions: Xin Sun made substantial contributions to the conception and design of the work and contributed to collecting the data and drafting the manuscript. Xiaomei Yang contributed to collecting the data and drafting the manuscript. Wenjuan Chen and Juan Chen contributed to collecting the data; Xiujuan Qu helped design the manuscript; Ying Chen and Jinglei Qu helped design and revise the manuscript.\u003c/p\u003e\n\u003cp\u003eEthics approval: Not appliable.\u003c/p\u003e\n\u003cp\u003eConsent to participate: Informed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003cp\u003eConsent to publication: A written informed consent for publication was obtained.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eJeong, S., et al., Re: Colon cancer survival rates with the new American Joint Committee on Cancer sixth edition staging. 2005. 97(22): p. 1705-6; author reply 1706-7. DOI: 10.1093/jnci/dji383\u003c/li\u003e\n\u003cli\u003eSundermeyer, M., et al., Changing patterns of bone and brain metastases in patients with colorectal cancer. 2005. 5(2): p. 108-13. DOI: 10.3816/ccc.2005.n.022\u003c/li\u003e\n\u003cli\u003e[Chinese expert consensus on multidisciplinary treatment of bone metastasis from colorectal cancer (2020 version)]. Zhonghua Zhong Liu Za Zhi, 2020. 42(6): p. 433-437. DOI: 10.3760/cma.j.cn112152-20200402-00295\u003c/li\u003e\n\u003cli\u003eO\u0026apos;Sullivan, G.J., F.L. Carty, and C.G. Cronin, Imaging of bone metastasis: An update. World J Radiol, 2015. 7(8): p. 202-11. DOI: 10.4329/wjr.v7.i8.202\u003c/li\u003e\n\u003cli\u003eHuang, Q. and X. Ouyang, Biochemical-markers for the diagnosis of bone metastasis: a clinical review. Cancer Epidemiol, 2012. 36(1): p. 94-8. DOI: 10.1016/j.canep.2011.02.001\u003c/li\u003e\n\u003cli\u003eMitchell, M. and P.J.R.a.r.p.o.t.R.S.o.N.A. Logan, Inc, Radiation-induced changes in bone. 1998. 18(5): p. 1125-36; quiz 1242-3. DOI: 10.1148/radiographics.18.5.9747611\u003c/li\u003e\n\u003cli\u003eKim, J., et al., Proceedings: Time dose factors in radiation induced osteitis. 1974. 120(3): p. 684-90. DOI: 10.2214/ajr.120.3.684\u003c/li\u003e\n\u003cli\u003eMeixel, A.J., et al., From radiation osteitis to osteoradionecrosis: incidence and MR morphology of radiation-induced sacral pathologies following pelvic radiotherapy. Eur Radiol, 2018. 28(8): p. 3550-3559. DOI: 10.1007/s00330-018-5325-2\u003c/li\u003e\n\u003cli\u003eBluemke, D., E. Fishman, and W.J.R.a.r.p.o.t.R.S.o.N.A. Scott, Inc, Skeletal complications of radiation therapy. 1994. 14(1): p. 111-21. DOI: 10.1148/radiographics.14.1.8128043\u003c/li\u003e\n\u003cli\u003eYousem, D.M., et al., Treated invasive cervical carcinoma. Utility of computed tomography in distinguishing between skeletal metastases and radiation necrosis. Clin Imaging, 1989. 13(2): p. 147-53. DOI: 10.1016/0899-7071(89)90098-3\u003c/li\u003e\n\u003cli\u003eYoshioka, H., et al., MR imaging of radiation osteitis in the sacroiliac joints. 2000. 18(2): p. 125-8. DOI: 10.1016/s0730-725x(99)00129-0\u003c/li\u003e\n\u003cli\u003eUgurluer, G., et al., Bone complications after pelvic radiation therapy: evaluation with MRI. J Med Imaging Radiat Oncol, 2014. 58(3): p. 334-40. DOI: 10.1111/1754-9485.12176\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table","content":"\u003cp\u003eTable 1: Summary of the characteristics and treatments of the two cases\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.545126353790614%\" valign=\"top\"\u003e\n \u003cp\u003epatients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.49097472924188%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.96389891696751%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.545126353790614%\" valign=\"top\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.49097472924188%\" valign=\"top\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.96389891696751%\" valign=\"top\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.545126353790614%\" valign=\"top\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.49097472924188%\" valign=\"top\"\u003e\n \u003cp\u003efemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.96389891696751%\" valign=\"top\"\u003e\n \u003cp\u003efemale\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.545126353790614%\" valign=\"top\"\u003e\n \u003cp\u003eRace\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.49097472924188%\" valign=\"top\"\u003e\n \u003cp\u003eAsian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.96389891696751%\" valign=\"top\"\u003e\n \u003cp\u003eAsian\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.545126353790614%\" valign=\"top\"\u003e\n \u003cp\u003eSite of the cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.49097472924188%\" valign=\"top\"\u003e\n \u003cp\u003esigmoid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.96389891696751%\" valign=\"top\"\u003e\n \u003cp\u003erectum\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.545126353790614%\" valign=\"top\"\u003e\n \u003cp\u003eStaging after surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.49097472924188%\" valign=\"top\"\u003e\n \u003cp\u003epT4bN0M0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.96389891696751%\" valign=\"top\"\u003e\n \u003cp\u003epT4bN0M0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.545126353790614%\" valign=\"top\"\u003e\n \u003cp\u003eRadiotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.49097472924188%\" valign=\"top\"\u003e\n \u003cp\u003e50.4 Gy in28 frictions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.96389891696751%\" valign=\"top\"\u003e\n \u003cp\u003e50.4 Gy in28 frictions\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.545126353790614%\" valign=\"top\"\u003e\n \u003cp\u003eSite of metastasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.49097472924188%\" valign=\"top\"\u003e\n \u003cp\u003eperitoneal cavity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.96389891696751%\" valign=\"top\"\u003e\n \u003cp\u003eleft side\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.545126353790614%\" valign=\"top\"\u003e\n \u003cp\u003eSite of RO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.49097472924188%\" valign=\"top\"\u003e\n \u003cp\u003eSacrum, ilium\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.96389891696751%\" valign=\"top\"\u003e\n \u003cp\u003eSacrum, ilium\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.545126353790614%\" valign=\"top\"\u003e\n \u003cp\u003eMMR protein analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.49097472924188%\" valign=\"top\"\u003e\n \u003cp\u003eMSS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.96389891696751%\" valign=\"top\"\u003e\n \u003cp\u003eMSS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.545126353790614%\" valign=\"top\"\u003e\n \u003cp\u003eGene test\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.49097472924188%\" valign=\"top\"\u003e\n \u003cp\u003esomatic mutations of KRAS, FGFR and PIK3CA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.96389891696751%\" valign=\"top\"\u003e\n \u003cp\u003esomatic mutations of KRAS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Radiation osteitis, radiotherapy, pelvis, diagnosis, bone metastasis","lastPublishedDoi":"10.21203/rs.3.rs-4196745/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4196745/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eRadiation osteitis (RO) is one of the bone complications arising after radiotherapy (RT). Limited to atypical manifestation in imaging. RO is difficult to diagnose, and sometimes, it could be considered as an early bone metastasis (BM), resulting in improper treatment. Thus, it’s vital to provide reliable evidence to clarify the isolated bone changes. Herein, we reported two advanced colorectal cancer (CRC) patients with atypical, isolated bone change in imaging, and both had underwent postoperative chemotherapy and radiotherapy. After medical imaging and clinical laboratory tests, the isolated bone change was finally confirmed to be RO rather than BM. The case series presented precision assessment for differentiating RO from BM, which may change the treatment strategy of this subgroup of patients.\u003c/p\u003e\n\u003cp\u003eKeywords: Radiation osteitis, radiotherapy, pelvis, diagnosis, bone metastasis.\u003c/p\u003e","manuscriptTitle":"Is the isolated bone change in advanced colorectal cancer a necessarily malignant metastasis? A case series","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-04 19:45:19","doi":"10.21203/rs.3.rs-4196745/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"89fb1627-e6f5-4d27-b18a-134165680fe1","owner":[],"postedDate":"April 4th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-04-05T13:28:44+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-04 19:45:19","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4196745","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4196745","identity":"rs-4196745","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}