Impact of PET-CT Interpretation on SBRT Planning: A Case of Pseudoprogression From Resolving Pneumonia During Pembrolizumab

Impact of PET-CT Interpretation on SBRT Planning: A Case of Pseudoprogression From Resolving Pneumonia During Pembrolizumab | 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 Impact of PET-CT Interpretation on SBRT Planning: A Case of Pseudoprogression From Resolving Pneumonia During Pembrolizumab Harshita Yepuri, Bhavik Singh, Justin Steinman This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8734909/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract Immune checkpoint inhibitors have transformed the management of metastatic non-small cell lung cancer (NSCLC) but can produce atypical fluorodeoxyglucose (FDG) positron emission tomography (PET) findings that mimic disease progression. We report a case of a 70-year-old woman with metastatic NSCLC on pembrolizumab who developed a new hypermetabolic left lower lobe (LLL) lesion suggestive of oligoprogression. Short-interval imaging at computed tomography (CT) simulation demonstrated near-complete resolution of the lesion, consistent with resolving pneumonia rather than true progression, thereby averting unnecessary stereotactic body radiotherapy (SBRT). Concurrently, a markedly FDG-avid upper-extremity abscess required substantial modification of SBRT immobilization and beam-arc design for treatment of the persistent left upper lobe (LUL) primary tumor. This case underscores the diagnostic pitfalls of PET imaging during immunotherapy and highlights the importance of cautious interpretation, clinical correlation, and adaptive radiation planning in the setting of atypical or inflammatory findings. immunotherapy non-small cell lung cancer pembrolizumab pneumonia stereotactic ablative body radiotherapy Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Background NSCLC constitutes the majority of lung cancer cases and is the leading cause of cancer death worldwide [ 1 ]. This category includes multiple subsets, including adenocarcinoma, squamous cell carcinoma, and large cell carcinomas [ 1 ]. In terms of first-line systemic treatment for metastatic disease, the initial treatment is often medically based with radiation reserved for the consolidative setting. Given that NSCLC is frequently PD-L1 positive, the use of immune checkpoint inhibitors such as pembrolizumab has become common practice. This therapy has been associated with improved response and survival rates, but can create variations in radiographic patterns of response [ 2 ]. During immunotherapy, distinguishing true progression from inflammatory change, infection, or pseudoprogression on FDG PET-CT is a recognized challenge [ 3 ]. Oligoprogression, which is a progression at a limited number of sites while other disease sites remain controlled, is an especially important scenario as it may prompt the use of local ablative therapies such as SBRT [ 4 ]. Correct identification of true oligoprogression is integral in avoiding unnecessary or inappropriate radiation [ 4 ]. Furthermore, incidental hypermetabolic lesions on PET may potentially represent significant non-malignant findings that influence the subsequent treatment plan. There are few cases in which unexpected extra-thoracic FDG-avid lesions complicate the patient setup or SBRT delivery [ 5 , 6 ]. We describe a patient with metastatic NSCLC on first-line pembrolizumab who demonstrated apparent oligoprogression on PET imaging, which was later determined to be resolving pneumonia, and who simultaneously exhibited an unexpected intensely FDG-avid upper-extremity abscess that required major modification of radiation therapy position and arc planning. This case underscores the importance of careful PET interpretation and highlights practical and technical considerations in SBRT delivery. Case Presentation A 70-year-old female with metastatic NSCLC presented in June 2025 for evaluation of a newly identified hypermetabolic pulmonary lesion. She was initially diagnosed in early June 2024 and was considered for definitive chemoradiation. However, her baseline staging PET-CT in mid-June 2024 demonstrated distant metastatic disease, excluding her from curative-intent therapy (Fig. 1 ). She was subsequently initiated on single-agent pembrolizumab in July 2024. A restaging PET-CT performed in December 2024 demonstrated interval improvement in her metastatic burden with persistent FDG-avid activity in the known LUL primary mass and several residual hypermetabolic lymph nodes (Figs. 2 – 3 ). Her next surveillance PET-CT in May 2025 showed continued decreased size and uptake in previously documented metastatic sites with stable hypermetabolism in the LUL tumor (Fig. 4 ). However, a new LLL hypermetabolic mass was identified and interpreted as possible oligoprogressive disease versus treatment-related inflammatory change (Figs. 5 – 8 ). Because the patient had not received any prior thoracic radiation, the new finding was presumed to represent true oligoprogression, and she was referred for consideration of SBRT. At the time of CT simulation in June 2025, the LLL lesion had nearly resolved, with no residual solid component visualized (Figs. 9 – 10 ). This rapid radiographic improvement was inconsistent with neoplastic progression and instead favored a resolving infectious or inflammatory process, and appeared to be most consistent with pneumonia. Given this interval resolution, SBRT to the LLL was deferred. Treatment planning proceeded only for the persistent dominant LUL mass, which remained metabolically active and radiographically stable despite systemic therapy. In addition, CT simulation required modification of standard immobilization technique due to symptomatic right upper-extremity abscess that precluded bilateral arm elevation. Under typical lung SBRT protocols, patients are positioned supine in a vac-lok cradle with both arms raised on a wingboard to optimize thoracic clearance for full-arc beam delivery. In this case, only the left arm could be positioned on the wingboard, while the right arm was maintained in an akimbo position. Because the target lesion was located in the left hemithorax, treatment planning incorporated left-sided partial arcs, which permitted adequate target coverage while minimizing unintended dose to the right upper extremity. The patient ultimately underwent SBRT to the LUL lesion, while the LLL abnormality required no local intervention. Her systemic disease remained otherwise controlled on pembrolizumab. Discussion Atypical response patterns including pseudoprogression and immune-related inflammatory changes are well documented in patients treated with PD-1 inhibitors [ 7 , 8 ]. Immune checkpoint inhibitors such as pembrolizumab have transformed the management of advanced NSCLC but have also introduced atypical response patterns and imaging pitfalls. These agents can induce inflammatory or immune-mediated processes that appear FDG-avid on PET-CT and closely mimic metastatic progression. FDG-PET is particularly susceptible to false-positive findings in patients receiving immunotherapy due to immune cell infiltration and cytokine-driven inflammation [ 9 , 10 ]. Reported manifestations include pseudoprogression, immune-related pneumonitis, retroperitoneal inflammation, sarcoid-like granulomatous reactions, mesenteric panniculitis, and biliary inflammation. Notably, these abnormalities can occur both during active therapy and 6–12 months after treatment has been discontinued, reflecting the prolonged immunologic activation associated with PD-1 blockade [ 11 , 12 , 13 ]. Because these processes can often be indistinguishable from true tumor progression on PET-CT alone, careful clinical correlation and repeat imaging or histologic confirmation are essential. The potential misinterpretation of immune-mediated inflammation as cancer progression has significant clinical consequences. Prior studies have demonstrated that premature discontinuation of immune checkpoint inhibitors based on imaging alone may deprive patients of durable disease control [ 14 , 15 ]. Inappropriate attribution of PET-avid lesions to metastatic spread may result in unnecessary radiation therapy, premature discontinuation of effective systemic agents, or transition to more cytotoxic or ineffective chemotherapy regimens. In this case, the interval resolution of the LLL lesion on CT simulation demonstrated that the PET abnormality most likely represented resolving pneumonia rather than oligoprogressive disease, thereby preventing an unnecessary course of SBRT. SBRT to the persistent LUL primary tumor was appropriate, given the overall control of systemic disease and the established role of local ablative therapy in oligopersistent and oligometastatic NSCLC. Randomized trials have demonstrated improved outcomes with local consolidative therapy in carefully selected patients [ 16 , 17 ]. When immune-related adverse events are confirmed, management typically involves discontinuation of the immune checkpoint inhibitor and, in some cases, corticosteroid therapy, which has been shown to reverse inflammatory toxicity in multiple reports [ 18 , 19 ]. This case underscores that interpretation of PET imaging in the context of ongoing or recently discontinued immunotherapy is complex and short-interval imaging can be crucial to avoid overtreatment and to guide appropriate use of local therapies. Conclusion This case highlights the complexity of interpreting new PET-avid pulmonary lesions in a patient with metastatic NSCLC receiving immunotherapy. Recognizing atypical or inflammatory patterns is critical, as these findings can significantly alter management decisions. It emphasizes the importance of correlating metabolic findings with clinical behavior and the value of short-interval reassessment before committing to local ablative therapy. Declarations Ethics approval and consent to participate Ethics approval was waived for this study as it describes a single retrospective case report. Informed consent for participation was obtained through the treating physician in accordance with institutional policies. Consent for publication Written informed consent for publication of the patient’s clinical details and imaging was obtained through the treating physician, and all data were fully anonymized prior to submission. Availability of data and materials Not applicable. Competing interests The authors declare that they have no competing interests. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Authors’ Contributions All authors acquired, analyzed, and interpreted the data. HY and BS drafted the manuscript. All authors performed a critical review of the manuscript for important intellectual content. JS designed and conceptualized the project. JS supervised the project. Acknowledgements Not applicable. References Clark SB, Alsubait S. Non-Small Cell Lung Cancer: Non-Small Cell Lung Cancer. StatPearls, editor: Treasure Island (FL): StatPearls Publishing, 2025; https://www.ncbi.nlm.nih.gov/books/NBK562307/ . Lackovic LN, Tomic MS, Novakovic M et al. Pembrolizumab in the treatment of non-small cell lung cancer-experiences from clinical practice. 2025, 12:1635626. 10.3389/fmed.2025.1635626 Ma Y, Wang Q, Dong Q. How to differentiate pseudoprogression from true progression in cancer patients treated with immunotherapy. Am J Cancer Res. 2019;1:1546–53. Cheung P. Stereotactic body radiotherapy for oligoprogressive cancer. Br J Radiol. 2016;89:20160251. 10.1259/bjr.20160251 . Karupakula E. Physiological FDG avid uptake in the lower thoracic spinal cord.. 192025. 10.53347/rID-178635 Singhvi M, Lee P. Illustrative cases of false positive biopsies after stereotactic body radiation therapy for lung cancer based on abnormal FDG-PET-CT imaging. BMJ Case Rep. 2013;2013:2012007967. 10.1136/bcr-2012-007967 . Gosangi B, McIntosh L, Keraliya A, Irugu DVK, Baheti A, Khandelwal A, Thomas R, Braschi-Amirfarzan M. Imaging features of toxicities associated with immune checkpoint inhibitors. Eur J Radiol Open. 2022;9:100434. PMID: 35967881; PMCID: PMC9372737. Wolchok JD, Hoos A, O'Day S, Weber JS, Hamid O, Lebbé C, Maio M, Binder M, Bohnsack O, Nichol G, Humphrey R, Hodi FS. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res. 2009;15(23):7412–20. 10.1158/1078-0432.CCR-09-1624 . Epub 2009 Nov 24. PMID: 19934295. Shroff GS, Strange CD, Ahuja J, et al. Imaging of Immune Checkpoint Inhibitor Immunotherapy for Non-Small Cell Lung Cancer. Radiographics. 2022;42(7):1956–74. Castello A, Rossi S, Mazziotti E, Toschi L, Lopci E. Hyperprogressive Disease in Patients with Non-Small Cell Lung Cancer Treated with Checkpoint Inhibitors: The Role of 18F-FDG PET/CT. J Nucl Med. 2020;61(6):821–6. 10.2967/jnumed.119.237768 . Epub 2019 Dec 20. PMID: 31862803. Khessib T, Franc B, Yang E, et al. Retroperitoneal inflammation detected on FDG PET/CT in a patient on long-term immunotherapy. Clin Nucl Med. 2023;48:165–6. 10.1097/RLU.0000000000004513 . Posado-Domínguez L, Escribano-Iglesias M, Bellido-Hernández L, et al. Inflammatory mesenteric disease and sarcoidosis-like reaction in a patient with lung adenocarcinoma who received pembrolizumab: paraneoplastic syndrome, secondary to checkpoint inhibitor or chance finding? Curr Oncol. 2024;31:7319–29. 10.3390/curroncol31110540 . Wang H, Jin Y, Liu P, et al. Immune checkpoint inhibitor-related pneumonitis following discontinuation of pembrolizumab in a patient with advanced lung adenocarcinoma: a case report and literature review. BMC Pulm Med. 2024;24:597. 10.1186/s12890-024-03424-9 . McKinley BJ, Pai TS, Wolf EB, Li S, Correia GSC, Zhao Y, Manochakian R, Lou Y. Early discontinuation of immune checkpoint inhibitor therapy prior to disease progression in patients with metastatic non-small cell lung cancer: a survival analysis. Front Oncol. 2024;14:1417175. PMID: 38974234; PMCID: PMC11224446. da Silva IP, Zimmer L, Blay JY, Maio M, Larkin J, Grimm MO, Puri S, Butler MO, Patel S, Thakkar PK, Long GV, Melero I. Retreatment, rechallenge, and escalation with subsequent immune checkpoint inhibitor therapies across cancers after initial failure. ESMO Open. 2025;10(11):105833. Epub 2025 Nov 6. PMID: 41202502; PMCID: PMC12639429. Gomez DR, Tang C, Zhang J, Blumenschein GR Jr, Hernandez M, Lee JJ, Ye R, Palma DA, Louie AV, Camidge DR, Doebele RC, Skoulidis F, Gaspar LE, Welsh JW, Gibbons DL, Karam JA, Kavanagh BD, Tsao AS, Sepesi B, Swisher SG, Heymach JV. Local Consolidative Therapy Vs. Maintenance Therapy or Observation for Patients With Oligometastatic Non-Small-Cell Lung Cancer: Long-Term Results of a Multi-Institutional, Phase II, Randomized Study. J Clin Oncol. 2019;37(18):1558–65. Epub 2019 May 8. PMID: 31067138; PMCID: PMC6599408. Iyengar P, Wardak Z, Gerber DE, Tumati V, Ahn C, Hughes RS, Dowell JE, Cheedella N, Nedzi L, Westover KD, Pulipparacharuvil S, Choy H, Timmerman RD. Consolidative Radiotherapy for Limited Metastatic Non-Small-Cell Lung Cancer: A Phase 2 Randomized Clinical Trial. JAMA Oncol. 2018;4(1):e173501. Epub 2018 Jan 11. PMID: 28973074; PMCID: PMC5833648. Matsumoto S, Watanabe K, Kobayashi N, et al. Pembrolizumab-induced secondary sclerosing cholangitis in a non-small cell lung cancer patient. Respirol Case Rep. 2020;8:00560. 10.1002/rcr2.560 . Amrane K, Le Meur C, Thuillier P, et al. Case report: Eosinophilic fasciitis induced by pembrolizumab with high FDG uptake on 18F-FDG-PET/CT. Front Med (Lausanne. 2022;9:1078560. 10.3389/fmed.2022.1078560 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 02 May, 2026 Reviewers invited by journal 21 Apr, 2026 Editor invited by journal 04 Feb, 2026 Editor assigned by journal 03 Feb, 2026 Submission checks completed at journal 03 Feb, 2026 First submitted to journal 29 Jan, 2026 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. 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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-8734909","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":631055645,"identity":"c5b2bce3-61d9-40ee-8adc-e57e03df172c","order_by":0,"name":"Harshita 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(MiP).\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8734909/v1/653e3b7c6e96b4fc343c629d.png"},{"id":108492452,"identity":"50ae1529-858f-4d6f-a9cd-b3c2f9cd9efd","added_by":"auto","created_at":"2026-05-05 09:57:47","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":82679,"visible":true,"origin":"","legend":"\u003cp\u003eFirst restaging PET-CT demonstrating initial response to immunotherapy with persisting dominant lesion in the left upper lobe and a few residual scattered hypermetabolic lymph nodes on MiP.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8734909/v1/341f23bfcc7a6964374fbfb9.png"},{"id":108384927,"identity":"012c465d-580f-4c0e-8d3e-663a619bd676","added_by":"auto","created_at":"2026-05-04 05:59:21","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":215352,"visible":true,"origin":"","legend":"\u003cp\u003eFirst restaging PET-CT demonstrating dominant hypermetabolic lesion in left upper lobe on axial view on PET component.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8734909/v1/6a3ee8dc356bf9ef669a7ae9.png"},{"id":108384920,"identity":"e6d08242-3167-4201-bbfe-5e3004272011","added_by":"auto","created_at":"2026-05-04 05:59:20","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":254218,"visible":true,"origin":"","legend":"\u003cp\u003eSecond restaging PET-CT demonstrating persistent hypermetabolic left upper lobe lesion on axial view of PET component.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-8734909/v1/e67dc1db6688afd2cd5948d6.png"},{"id":108384921,"identity":"9778e865-5cb5-4093-a6b7-5ec7f99c4cb7","added_by":"auto","created_at":"2026-05-04 05:59:20","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":222515,"visible":true,"origin":"","legend":"\u003cp\u003eSecond restaging PET-CT demonstrating new hypermetabolic lesion in the left lower lobe on axial view shown on PET component.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-8734909/v1/04873f73ac209cca43fd09dd.png"},{"id":108384922,"identity":"811d1178-4aa6-4202-8d5d-b08eee40691f","added_by":"auto","created_at":"2026-05-04 05:59:21","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":258249,"visible":true,"origin":"","legend":"\u003cp\u003eSecond restaging PET-CT demonstrating new hypermetabolic lesion in the left lower lobe on axial view shown on CT component.\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-8734909/v1/4b02da7611bef858268de4f9.png"},{"id":108492888,"identity":"86f1004d-53d2-433d-bf53-a15df89c04df","added_by":"auto","created_at":"2026-05-05 09:58:54","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":226873,"visible":true,"origin":"","legend":"\u003cp\u003eSecond restaging PET-CT demonstrating new hypermetabolic lesion in the left lower lobe on coronal view shown on PET component.\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-8734909/v1/d57d3a32dfb99184c589dd9e.png"},{"id":108384924,"identity":"4e6a8f5e-65b1-4553-afe0-5a9db1d44e30","added_by":"auto","created_at":"2026-05-04 05:59:21","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":199037,"visible":true,"origin":"","legend":"\u003cp\u003eSecond restaging PET-CT demonstrating new hypermetabolic lesion in the left lower lobe on coronal view shown on CT component.\u003c/p\u003e","description":"","filename":"8.png","url":"https://assets-eu.researchsquare.com/files/rs-8734909/v1/b7d2ffd7fe809fae03fab640.png"},{"id":108493194,"identity":"73fc9df6-52da-4a58-898c-7741ad2b6859","added_by":"auto","created_at":"2026-05-05 09:59:35","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":248206,"visible":true,"origin":"","legend":"\u003cp\u003eCT simulation demonstrating improvement in the previously demonstrated hypermetabolic left lower lobe lesion with resolving solid component on axial view.\u003c/p\u003e","description":"","filename":"9.png","url":"https://assets-eu.researchsquare.com/files/rs-8734909/v1/536d803bcad5d92a81d139fc.png"},{"id":108384926,"identity":"122b6cda-e21e-4a07-9474-1c56ba236343","added_by":"auto","created_at":"2026-05-04 05:59:21","extension":"png","order_by":10,"title":"Figure 10","display":"","copyAsset":false,"role":"figure","size":313847,"visible":true,"origin":"","legend":"\u003cp\u003eCT simulation demonstrating improvement in the previously demonstrated hypermetabolic left lower lobe lesion with resolving solid component on coronal view.\u003c/p\u003e","description":"","filename":"10.png","url":"https://assets-eu.researchsquare.com/files/rs-8734909/v1/8426c9a0cb5e06d13fec0259.png"},{"id":108803600,"identity":"660b3557-b5ec-443b-a723-c02c3b7300c4","added_by":"auto","created_at":"2026-05-08 15:00:11","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3323335,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8734909/v1/2d679166-4b54-4c7b-b768-91bc70e1dd3d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Impact of PET-CT Interpretation on SBRT Planning: A Case of Pseudoprogression From Resolving Pneumonia During Pembrolizumab","fulltext":[{"header":"Background","content":"\u003cp\u003eNSCLC constitutes the majority of lung cancer cases and is the leading cause of cancer death worldwide [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. This category includes multiple subsets, including adenocarcinoma, squamous cell carcinoma, and large cell carcinomas [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In terms of first-line systemic treatment for metastatic disease, the initial treatment is often medically based with radiation reserved for the consolidative setting. Given that NSCLC is frequently PD-L1 positive, the use of immune checkpoint inhibitors such as pembrolizumab has become common practice. This therapy has been associated with improved response and survival rates, but can create variations in radiographic patterns of response [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. During immunotherapy, distinguishing true progression from inflammatory change, infection, or pseudoprogression on FDG PET-CT is a recognized challenge [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOligoprogression, which is a progression at a limited number of sites while other disease sites remain controlled, is an especially important scenario as it may prompt the use of local ablative therapies such as SBRT [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Correct identification of true oligoprogression is integral in avoiding unnecessary or inappropriate radiation [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFurthermore, incidental hypermetabolic lesions on PET may potentially represent significant non-malignant findings that influence the subsequent treatment plan. There are few cases in which unexpected extra-thoracic FDG-avid lesions complicate the patient setup or SBRT delivery [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe describe a patient with metastatic NSCLC on first-line pembrolizumab who demonstrated apparent oligoprogression on PET imaging, which was later determined to be resolving pneumonia, and who simultaneously exhibited an unexpected intensely FDG-avid upper-extremity abscess that required major modification of radiation therapy position and arc planning. This case underscores the importance of careful PET interpretation and highlights practical and technical considerations in SBRT delivery.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 70-year-old female with metastatic NSCLC presented in June 2025 for evaluation of a newly identified hypermetabolic pulmonary lesion. She was initially diagnosed in early June 2024 and was considered for definitive chemoradiation. However, her baseline staging PET-CT in mid-June 2024 demonstrated distant metastatic disease, excluding her from curative-intent therapy (Fig. \u003cspan refid=\"Fig1\"\u003e1\u003c/span\u003e). She was subsequently initiated on single-agent pembrolizumab in July 2024.\u003c/p\u003e\n\u003cp\u003eA restaging PET-CT performed in December 2024 demonstrated interval improvement in her metastatic burden with persistent FDG-avid activity in the known LUL primary mass and several residual hypermetabolic lymph nodes (Figs. \u003cspan refid=\"Fig2\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Fig3\"\u003e3\u003c/span\u003e). Her next surveillance PET-CT in May 2025 showed continued decreased size and uptake in previously documented metastatic sites with stable hypermetabolism in the LUL tumor (Fig. \u003cspan refid=\"Fig4\"\u003e4\u003c/span\u003e). However, a new LLL hypermetabolic mass was identified and interpreted as possible oligoprogressive disease versus treatment-related inflammatory change (Figs. \u003cspan refid=\"Fig5\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Fig8\"\u003e8\u003c/span\u003e). Because the patient had not received any prior thoracic radiation, the new finding was presumed to represent true oligoprogression, and she was referred for consideration of SBRT.\u003c/p\u003e\n\u003cp\u003eAt the time of CT simulation in June 2025, the LLL lesion had nearly resolved, with no residual solid component visualized (Figs. \u003cspan refid=\"Fig9\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Fig10\"\u003e10\u003c/span\u003e). This rapid radiographic improvement was inconsistent with neoplastic progression and instead favored a resolving infectious or inflammatory process, and appeared to be most consistent with pneumonia. Given this interval resolution, SBRT to the LLL was deferred. Treatment planning proceeded only for the persistent dominant LUL mass, which remained metabolically active and radiographically stable despite systemic therapy. In addition, CT simulation required modification of standard immobilization technique due to symptomatic right upper-extremity abscess that precluded bilateral arm elevation. Under typical lung SBRT protocols, patients are positioned supine in a vac-lok cradle with both arms raised on a wingboard to optimize thoracic clearance for full-arc beam delivery. In this case, only the left arm could be positioned on the wingboard, while the right arm was maintained in an akimbo position. Because the target lesion was located in the left hemithorax, treatment planning incorporated left-sided partial arcs, which permitted adequate target coverage while minimizing unintended dose to the right upper extremity.\u003c/p\u003e\n\u003cp\u003eThe patient ultimately underwent SBRT to the LUL lesion, while the LLL abnormality required no local intervention. Her systemic disease remained otherwise controlled on pembrolizumab.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAtypical response patterns including pseudoprogression and immune-related inflammatory changes are well documented in patients treated with PD-1 inhibitors [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Immune checkpoint inhibitors such as pembrolizumab have transformed the management of advanced NSCLC but have also introduced atypical response patterns and imaging pitfalls. These agents can induce inflammatory or immune-mediated processes that appear FDG-avid on PET-CT and closely mimic metastatic progression. FDG-PET is particularly susceptible to false-positive findings in patients receiving immunotherapy due to immune cell infiltration and cytokine-driven inflammation [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Reported manifestations include pseudoprogression, immune-related pneumonitis, retroperitoneal inflammation, sarcoid-like granulomatous reactions, mesenteric panniculitis, and biliary inflammation. Notably, these abnormalities can occur both during active therapy and 6\u0026ndash;12 months after treatment has been discontinued, reflecting the prolonged immunologic activation associated with PD-1 blockade [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Because these processes can often be indistinguishable from true tumor progression on PET-CT alone, careful clinical correlation and repeat imaging or histologic confirmation are essential.\u003c/p\u003e \u003cp\u003eThe potential misinterpretation of immune-mediated inflammation as cancer progression has significant clinical consequences. Prior studies have demonstrated that premature discontinuation of immune checkpoint inhibitors based on imaging alone may deprive patients of durable disease control [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Inappropriate attribution of PET-avid lesions to metastatic spread may result in unnecessary radiation therapy, premature discontinuation of effective systemic agents, or transition to more cytotoxic or ineffective chemotherapy regimens. In this case, the interval resolution of the LLL lesion on CT simulation demonstrated that the PET abnormality most likely represented resolving pneumonia rather than oligoprogressive disease, thereby preventing an unnecessary course of SBRT.\u003c/p\u003e \u003cp\u003eSBRT to the persistent LUL primary tumor was appropriate, given the overall control of systemic disease and the established role of local ablative therapy in oligopersistent and oligometastatic NSCLC. Randomized trials have demonstrated improved outcomes with local consolidative therapy in carefully selected patients [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. When immune-related adverse events are confirmed, management typically involves discontinuation of the immune checkpoint inhibitor and, in some cases, corticosteroid therapy, which has been shown to reverse inflammatory toxicity in multiple reports [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. This case underscores that interpretation of PET imaging in the context of ongoing or recently discontinued immunotherapy is complex and short-interval imaging can be crucial to avoid overtreatment and to guide appropriate use of local therapies.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis case highlights the complexity of interpreting new PET-avid pulmonary lesions in a patient with metastatic NSCLC receiving immunotherapy. Recognizing atypical or inflammatory patterns is critical, as these findings can significantly alter management decisions. It emphasizes the importance of correlating metabolic findings with clinical behavior and the value of short-interval reassessment before committing to local ablative therapy.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthics approval was waived for this study as it describes a single retrospective case report. Informed consent for participation was obtained through the treating physician in accordance with institutional policies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication of the patient\u0026rsquo;s clinical details and imaging was obtained through the treating physician, and all data were fully anonymized prior to submission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors acquired, analyzed, and interpreted the data.\u003c/p\u003e\n\u003cp\u003eHY and BS drafted the manuscript.\u003c/p\u003e\n\u003cp\u003eAll authors performed a critical review of the manuscript for important intellectual content.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eJS designed and conceptualized the project.\u003c/p\u003e\n\u003cp\u003eJS supervised the project.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eClark SB, Alsubait S. 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Respirol Case Rep. 2020;8:00560. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/rcr2.560\u003c/span\u003e\u003cspan address=\"10.1002/rcr2.560\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmrane K, Le Meur C, Thuillier P, et al. Case report: Eosinophilic fasciitis induced by pembrolizumab with high FDG uptake on 18F-FDG-PET/CT. Front Med (Lausanne. 2022;9:1078560. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fmed.2022.1078560\u003c/span\u003e\u003cspan address=\"10.3389/fmed.2022.1078560\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"bmc-pulmonary-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pulm","sideBox":"Learn more about [BMC Pulmonary Medicine](http://bmcpulmmed.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pulm/default.aspx","title":"BMC Pulmonary Medicine","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"immunotherapy, non-small cell lung cancer, pembrolizumab, pneumonia, stereotactic ablative body radiotherapy","lastPublishedDoi":"10.21203/rs.3.rs-8734909/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8734909/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eImmune checkpoint inhibitors have transformed the management of metastatic non-small cell lung cancer (NSCLC) but can produce atypical fluorodeoxyglucose (FDG) positron emission tomography (PET) findings that mimic disease progression. We report a case of a 70-year-old woman with metastatic NSCLC on pembrolizumab who developed a new hypermetabolic left lower lobe (LLL) lesion suggestive of oligoprogression. Short-interval imaging at computed tomography (CT) simulation demonstrated near-complete resolution of the lesion, consistent with resolving pneumonia rather than true progression, thereby averting unnecessary stereotactic body radiotherapy (SBRT). Concurrently, a markedly FDG-avid upper-extremity abscess required substantial modification of SBRT immobilization and beam-arc design for treatment of the persistent left upper lobe (LUL) primary tumor. This case underscores the diagnostic pitfalls of PET imaging during immunotherapy and highlights the importance of cautious interpretation, clinical correlation, and adaptive radiation planning in the setting of atypical or inflammatory findings.\u003c/p\u003e","manuscriptTitle":"Impact of PET-CT Interpretation on SBRT Planning: A Case of Pseudoprogression From Resolving Pneumonia During Pembrolizumab","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-04 05:59:15","doi":"10.21203/rs.3.rs-8734909/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"256842368526355538329673772827340252647","date":"2026-05-02T18:38:20+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-21T08:33:53+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-04T18:04:35+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-03T13:27:15+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-03T13:24:36+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pulmonary Medicine","date":"2026-01-29T19:51:49+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pulmonary-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pulm","sideBox":"Learn more about [BMC Pulmonary Medicine](http://bmcpulmmed.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pulm/default.aspx","title":"BMC Pulmonary Medicine","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2befb09c-5299-4a47-b27d-62eb3e041035","owner":[],"postedDate":"May 4th, 2026","published":true,"recentEditorialEvents":[{"type":"reviewerAgreed","content":"256842368526355538329673772827340252647","date":"2026-05-02T18:38:20+00:00","index":66,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-04T05:59:16+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-04 05:59:15","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8734909","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8734909","identity":"rs-8734909","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}