{"product_id":"the-abscopal-effect-in-non-small-cell-lung-cancer-when-treating-one-tumor-shrinks-tumors-elsewhere-in-the-body","title":"The Abscopal Effect in Non-Small Cell Lung Cancer: When Treating One Tumor Shrinks Tumors Elsewhere in the Body","description":"\u003cp\u003eThe abscopal effect — the shrinking of tumors far from the site where radiation or a tumor-destroying procedure was applied — was first described in 1953 and long considered rare. This narrative review gathers the evidence in non-small cell lung cancer (NSCLC). The review shows that radiotherapy, cryoablation, microwave ablation, and pulsed electric field therapy can all trigger immune activation that reaches distant tumors. This is especially true when these treatments are combined with immune checkpoint inhibitors. Because standard response criteria (RECIST v1.1) often miss these out-of-field responses, the authors argue the true incidence is likely underestimated. They propose a working definition: regression (complete or partial response by iRECIST) of one or more non-irradiated lesions distant from the treated site, confirmed by follow-up imaging within 4 to 8 weeks.\u003c\/p\u003e\n\n\u003ch1\u003eDefining the abscopal effect in non-small cell lung cancer in the era of immunotherapy and lung ablation treatment: a narrative review.\u003c\/h1\u003e\n\n\u003ch2\u003eTable of Contents\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003e\u003ca href=\"#ddn-key-points\"\u003eKey Points\u003c\/a\u003e\u003c\/li\u003e\n\n\u003cli\u003e\u003ca href=\"#background\"\u003eBackground: What Is the Abscopal Effect?\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#measuring\"\u003eHow Doctors Measure Tumor Response: RECIST and iRECIST\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#aim\"\u003eThe Goal of This Review\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#radiation-biology\"\u003eHow Radiotherapy Can Trigger an Immune Attack Far From the Treated Tumor\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#radiotherapy-cases\"\u003eReal Patient Cases: Abscopal Effects After Radiotherapy\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#ablation-biology\"\u003eHow Lung Ablation Triggers Systemic Immune Responses\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#ablation-cases\"\u003eReal Patient Cases: Abscopal Effects After Ablation\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#combo\"\u003eCombining Radiotherapy With Immunotherapy\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#trials\"\u003eWhat the Prospective Clinical Trials Show\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#discussion\"\u003eWhat This Evidence Means for Patients\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#definition\"\u003eThe Proposed Working Definition\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#limitations\"\u003eLimitations of the Current Evidence\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#recommendations\"\u003eRecommendations and What Comes Next\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#ddn-faq\"\u003eFrequently Asked Questions\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#source\"\u003eSource Information\u003c\/a\u003e\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003c!-- ddn:keypoints:start --\u003e\n\u003ch2 id=\"ddn-key-points\"\u003eKey Points\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003eThe abscopal effect is when untreated tumors shrink after treatment to another site; it was first described in 1953 and is still considered uncommon.\u003c\/li\u003e\n\u003cli\u003eRadiation can trigger immune activation that reaches distant tumors, but it can also suppress immunity, which may limit how often this happens.\u003c\/li\u003e\n\u003cli\u003eAblation techniques like cryoablation and microwave ablation can release tumor antigens and stimulate immune responses, but evidence for abscopal effects remains limited to case reports.\u003c\/li\u003e\n\u003cli\u003eStandard RECIST v1.1 criteria may miss out-of-field tumor shrinkage; iRECIST helps with immunotherapy patterns but still does not systematically record abscopal responses.\u003c\/li\u003e\n\u003cli\u003eA proposed definition for NSCLC requires regression of non-irradiated lesions by iRECIST, confirmed by imaging within 4 to 8 weeks after localized therapy.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c!-- ddn:keypoints:end --\u003e\n\n\n\u003ch2 id=\"background\"\u003eBackground: What Is the Abscopal Effect?\u003c\/h2\u003e\n\n\u003cp\u003eThe abscopal effect is a phenomenon in which tumors that were never directly treated begin to shrink after treatment is delivered somewhere else in the body. The term was first coined in 1953 by a researcher named Mole, who observed that distant, non-irradiated tumors regressed after localized radiotherapy (radiation treatment aimed at one specific area).\u003c\/p\u003e\n\n\u003cp\u003eSince that first report, the abscopal effect has been documented in several cancer types, including \u003cstrong\u003ebreast cancer, melanoma, and lung cancer\u003c\/strong\u003e. For decades it was considered a medical curiosity. That changed as immunotherapy entered routine care for advanced NSCLC. Immunotherapy means treatments that help the immune system fight cancer. New local treatment strategies also entered routine care, such as lung ablation. Lung ablation uses extreme heat, cold, or electrical pulses to destroy tumors.\u003c\/p\u003e\n\n\u003cp\u003eDespite growing interest, the abscopal effect still appears uncommon. The authors of this review point to a key unanswered question: is the effect truly rare, or are doctors simply failing to recognize it? In routine practice, a shrinking untreated tumor may be attributed to other causes, or it may not be formally recorded at all. That uncertainty is the central problem this review addresses.\u003c\/p\u003e\n\n\u003ch2 id=\"measuring\"\u003eHow Doctors Measure Tumor Response: RECIST and iRECIST\u003c\/h2\u003e\n\n\u003cp\u003eTo understand why abscopal effects may go unnoticed, you need to understand how clinical trials measure whether a cancer treatment is working. The standard tool is called \u003cstrong\u003eRECIST version 1.1\u003c\/strong\u003e (Response Evaluation Criteria in Solid Tumors).\u003c\/p\u003e\n\n\u003cp\u003eHere is how RECIST v1.1 works in practice:\u003c\/p\u003e\n\n\u003cul\u003e\n\u003cli\u003eBefore treatment begins, doctors select \"target lesions\" — up to \u003cstrong\u003efive in total, with no more than two per organ\u003c\/strong\u003e.\u003c\/li\u003e\n\u003cli\u003eThese target lesions should represent the patient's overall tumor burden.\u003c\/li\u003e\n\u003cli\u003eSome lesions cannot serve as targets. For example, tumors in areas previously treated with local or regional therapy are considered \"non-measurable.\"\u003c\/li\u003e\n\u003cli\u003eAll remaining tumors are labeled \"non-target lesions.\"\u003c\/li\u003e\n\u003cli\u003eDoctors can still declare disease progression based on non-target lesions if there is clear evidence the cancer is growing.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eHere is the crux of the problem. While clear progression in non-target lesions counts, \u003cstrong\u003eclear improvement in non-target lesions — exactly what happens in an abscopal effect — may not be captured at all\u003c\/strong\u003e within the RECIST v1.1 framework. A distant tumor shrinking on its own could simply be missed.\u003c\/p\u003e\n\n\u003cp\u003eTo address unusual response patterns, researchers developed the \u003cstrong\u003eiRECIST criteria\u003c\/strong\u003e (immune Response Evaluation Criteria in Solid Tumors). This system was designed specifically for immunotherapy, which can cause a confusing pattern called \u003cstrong\u003epseudo-progression\u003c\/strong\u003e — an initial increase in tumor size or the appearance of new lesions, followed later by stabilization or shrinkage.\u003c\/p\u003e\n\n\u003cp\u003ePseudo-progression happens because immune cells flood into the tumor, making it look larger on a scan before it actually shrinks. Under RECIST v1.1, this would immediately be labeled progressive disease (PD). Under iRECIST, it is instead labeled \u003cstrong\u003eunconfirmed progressive disease (iUPD)\u003c\/strong\u003e. The progression must be confirmed on a follow-up scan at least \u003cstrong\u003e4 weeks later\u003c\/strong\u003e before doctors call it \u003cstrong\u003econfirmed progressive disease (iCPD)\u003c\/strong\u003e.\u003c\/p\u003e\n\n\u003cp\u003eThe authors note that iRECIST partially solves the problem — but not entirely. Unequivocal regression of a tumor outside the treatment field is still not systematically recorded in most trials.\u003c\/p\u003e\n\n\u003ch2 id=\"aim\"\u003eThe Goal of This Review\u003c\/h2\u003e\n\n\u003cp\u003eThe authors set out to do something no one had done systematically: build a consensus definition of the abscopal effect specifically for NSCLC. They drew on evidence from single-treatment and multi-treatment trials to guide future research and everyday clinical decisions.\u003c\/p\u003e\n\n\u003cp\u003eWhy does a definition matter? Without one, researchers cannot compare studies, doctors cannot reliably recognize the effect, and patients may not receive credit for a response that is actually happening. A shared vocabulary is the first step toward integrating abscopal responses into routine care.\u003c\/p\u003e\n\n\u003ch2 id=\"radiation-biology\"\u003eHow Radiotherapy Can Trigger an Immune Attack Far From the Treated Tumor\u003c\/h2\u003e\n\n\u003cp\u003eRadiotherapy does two opposing things to the tumor microenvironment (the mix of cells, blood vessels, and signaling molecules surrounding a tumor). It activates the immune system — and it can also suppress it.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eThe activating side:\u003c\/strong\u003e Ionizing radiation causes \u003cstrong\u003eimmunogenic cell death\u003c\/strong\u003e, a form of cell death that alarms the immune system rather than hiding from it. Dying tumor cells expose a protein called calreticulin on their surface and release \u003cstrong\u003edanger-associated molecular patterns (DAMPs)\u003c\/strong\u003e, including HMGB1 and heat shock proteins. These signals include cytokines (immune signaling proteins) such as TNF-α, IL-6, TGF-β, and IL-8. These signals also include reactive oxygen and nitrogen species. These signals switch on dendritic cells, macrophages, and natural killer (NK) cells inside the tumor.\u003c\/p\u003e\n\n\u003cp\u003eDAMPs then bind to receptors such as TLR4 on dendritic cells. This drives antigen presentation through MHC-I molecules and helps dendritic cells mature. At the same time, upregulation of MHC-II helps activate CD4+ T cells. Radiation-induced DNA damage also switches on the \u003cstrong\u003ecGAS-STING pathway\u003c\/strong\u003e, which boosts type I interferon production, cross-presentation of tumor antigens, and priming of CD8+ cytotoxic T lymphocytes (CTLs) — the immune system's killer cells.\u003c\/p\u003e\n\n\u003cp\u003eThese CTLs can then travel through the bloodstream to distant, non-irradiated tumors. There they infiltrate the tumor microenvironment and attack cancer cells carrying the same neoantigens (unique proteins found on tumor cells). The result is shrinkage of distant tumors — the hallmark of the abscopal effect.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eThe suppressing side:\u003c\/strong\u003e Radiotherapy can also backfire. It can cause accumulation of myeloid-derived suppressor cells (MDSCs) and increase PD-L1 on tumor cells, both of which restrain T-cell activity in the tumor microenvironment. This is likely one reason the abscopal effect is not more common. This is also one reason combining radiation with immune checkpoint inhibitors makes biological sense. Immune checkpoint inhibitors are drugs that release the brakes on T cells.\u003c\/p\u003e\n\n\u003ch2 id=\"radiotherapy-cases\"\u003eReal Patient Cases: Abscopal Effects After Radiotherapy\u003c\/h2\u003e\n\n\u003cp\u003eSeveral individual patient reports describe abscopal effects in NSCLC after radiotherapy alone. Together they show the phenomenon can occur even without systemic therapy.\u003c\/p\u003e\n\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003eRees et al.\u003c\/strong\u003e published one of the earliest cases. A patient with metastatic lung adenocarcinoma saw untreated lung metastases regress \u003cstrong\u003e20 months after radiotherapy\u003c\/strong\u003e was delivered to an esophageal lesion.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eVilinovszki et al.\u003c\/strong\u003e described an \u003cstrong\u003e81-year-old woman\u003c\/strong\u003e with recurrent metastatic squamous NSCLC who refused systemic therapy. After palliative radiotherapy to the bulk of the mediastinal tumor, durable regression appeared both at the treated site and in bone metastases that had received no radiation. At \u003cstrong\u003e25 months\u003c\/strong\u003e after treatment, she remained in remission at all sites.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eSakaguchi et al.\u003c\/strong\u003e reported abscopal regression of a vertebral metastasis after palliative irradiation of a right iliac bone lesion in a \u003cstrong\u003e94-year-old patient\u003c\/strong\u003e with EGFR-mutant NSCLC who was not fit for chemotherapy.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eA 2009 case\u003c\/strong\u003e described a \u003cstrong\u003e60-year-old man\u003c\/strong\u003e with stage IV NSCLC (KRAS and EGFR wild type — meaning no targetable mutations). He underwent removal of a cerebellar (brain) metastasis, whole-brain radiotherapy, and stereotactic radiosurgery (SRS, a highly precise form of radiation), followed by chemotherapy. He later progressed in the adrenal glands, lungs, liver, and brain. The brain metastases were treated with SRS. After radiation was completed, follow-up imaging showed \u003cstrong\u003ecomplete resolution of all extracranial disease without any additional systemic therapy\u003c\/strong\u003e. He stayed disease-free for more than \u003cstrong\u003e5 years\u003c\/strong\u003e.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eHamilton et al.\u003c\/strong\u003e described complete resolution of a pleural lung mass \u003cstrong\u003e3 months\u003c\/strong\u003e after stereotactic radiosurgery to a solitary brain metastasis.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eTakayama et al.\u003c\/strong\u003e saw regression of lung and mediastinal lesions after whole-brain radiotherapy and spinal radiotherapy in a patient with stage IV NSCLC.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eKuroda et al.\u003c\/strong\u003e described a \u003cstrong\u003e76-year-old woman\u003c\/strong\u003e with EGFR-mutant NSCLC in whom thoracic irradiation of a hilar lymph node metastasis led to complete disappearance of pulmonary metastases.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eTwo important points stand out. First, the abscopal effect can occur after radiotherapy alone, without any immunotherapy. Second, the abscopal effect can even occur after radiation to a brain metastasis. This is remarkable, because the blood–brain barrier usually limits what passes between the brain and the rest of the body. The blood–brain barrier is a protective filter around the brain.\u003c\/p\u003e\n\n\u003ch2 id=\"ablation-biology\"\u003eHow Lung Ablation Triggers Systemic Immune Responses\u003c\/h2\u003e\n\n\u003cp\u003eAblation destroys tumors locally using extreme cold, heat, or electrical pulses. Each technique triggers a somewhat different immune signature.\u003c\/p\u003e\n\n\u003ch3\u003eCryoablation (freezing)\u003c\/h3\u003e\n\n\u003cp\u003eCryoablation kills tumor cells by freezing them, but it also stimulates the immune system. Necrotic (dead) tumor cells release pro-inflammatory cytokines including \u003cstrong\u003eIL-12, IFN-γ, and TNF-α\u003c\/strong\u003e, along with tumor antigens that antigen-presenting cells capture and use to activate T-cell and B-cell responses. However, in tissue that is only partially frozen, apoptosis (programmed cell death) can release immunosuppressive signals such as IL-10 and TGF-β.\u003c\/p\u003e\n\n\u003cp\u003ePreclinical studies (lab and animal research) show that cryoablation generates tumor-specific immunity. Animals developed protection against previously ablated tumor lines, and growth of tumors on the opposite side of the body was suppressed — consistent with an abscopal effect. Mechanistically, cryoablation activates the \u003cstrong\u003eIFN-γ, IL-2\/STAT5, IL-6\/JAK\/STAT3, and type I interferon pathways\u003c\/strong\u003e. Single-cell transcriptomics (detailed gene-activity profiling) reveal enhanced antigen presentation and a transitional IFN-stimulated T-cell state that prolongs CD8+ effector activity. STING-TBK1 signaling contributes to the systemic response, and blocking type I interferons reduces it.\u003c\/p\u003e\n\n\u003cp\u003eIn patients, cryoablation increases circulating CD8+ T cells. Cryoablation also raises the ratio of CD8+ cells to regulatory T cells (Tregs, which normally suppress immune responses). Cryoablation reduces FoxP3+ Tregs. Cryoablation remodels the tumor microenvironment to favor immune infiltration.\u003c\/p\u003e\n\n\u003ch3\u003eMicrowave ablation (MWA)\u003c\/h3\u003e\n\n\u003cp\u003eMicrowave ablation of lung tumors produces measurable immune changes: an increase in cytotoxic CD8+ T cells and a decrease in Treg cells. The shift in helper T-cell subtypes is less clear. One study found significantly elevated Th1-associated cytokines — \u003cstrong\u003eIL-2, IFN-γ, TNF-α, and IL-12p70\u003c\/strong\u003e — while Th2-associated cytokines (IL-4 and IL-10) stayed unchanged. Another study found that IL-2 decreased in \u003cstrong\u003e59.1% of patients one month after percutaneous MWA\u003c\/strong\u003e, which the authors propose as a mechanism for Treg downregulation. More research on IL-2 is needed for a definitive answer.\u003c\/p\u003e\n\n\u003ch3\u003ePulsed electric field (PEF) therapy\u003c\/h3\u003e\n\n\u003cp\u003ePEF therapy uses short electrical pulses to kill tumor cells. It releases DAMPs such as HMGB1, which stimulate dendritic cells and tumor-specific CD8+ T cells. PEF also increases antigen-presenting cell activity, reduces Tregs and M2 macrophages, and modulates immune signaling pathways including IL-6, JAK–STAT, and Th17\/IL-17, with early activation followed by later downregulation. Importantly, PEF preserves the extracellular matrix and local blood vessels. That keeps tumor antigens intact and makes it easier for immune cells to get in — an advantage over heat-based ablation.\u003c\/p\u003e\n\n\u003ch2 id=\"ablation-cases\"\u003eReal Patient Cases: Abscopal Effects After Ablation\u003c\/h2\u003e\n\n\u003cp\u003eEvidence for abscopal effects after tumor ablation in metastatic NSCLC is scarce. So far, the literature consists mainly of isolated case reports.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eShao et al.\u003c\/strong\u003e reported a \u003cstrong\u003e69-year-old man\u003c\/strong\u003e with advanced squamous NSCLC who had already received \u003cstrong\u003efour different lines of systemic therapy\u003c\/strong\u003e. He then developed oligo-progression (growth in just a few spots) with enlargement of the primary lung tumor and mediastinal 4R and 7 lymph nodes. Because of severe COPD (chronic obstructive pulmonary disease), he could not tolerate radiotherapy to both sites. CT-guided microwave ablation was performed on the primary tumor only. Follow-up imaging showed gradual absorption of the ablated lung lesion and — simultaneously — \u003cstrong\u003eshrinkage of the untreated mediastinal lymph nodes\u003c\/strong\u003e, consistent with an abscopal effect.\u003c\/p\u003e\n\n\u003cp\u003eAbscopal effects from microwave ablation have also been reported in lung metastases from other cancer types, including endometrial and colorectal carcinoma, though some of this evidence comes from preclinical models.\u003c\/p\u003e\n\n\u003cp\u003eThe authors are clear about the limits here. These observations suggest ablation may trigger systemic immune activation through antigen release and inflammatory signaling. However, the current level of evidence remains limited. Unlike radiation-based strategies, which have been studied in multiple clinical trials, the immune-modulating effects of ablation techniques have not been well defined.\u003c\/p\u003e\n\n\u003ch2 id=\"combo\"\u003eCombining Radiotherapy With Immunotherapy\u003c\/h2\u003e\n\n\u003cp\u003eAdding an immune checkpoint inhibitor (a drug that releases the brakes on immune cells) to radiotherapy appears to amplify the abscopal effect. Multiple preclinical models support this combination.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eWei et al.\u003c\/strong\u003e studied antitumor activity at both the treated and distant tumor sites. They found that the strength of the abscopal response depended on \u003cstrong\u003ewhen\u003c\/strong\u003e the anti-PD-1 antibody was given relative to radiation. When PD-1 blockade followed local irradiation, it expanded polyfunctional CD8+ T cells inside the tumor, reduced dysfunctional CD8+ T cells, and triggered strong abscopal effects.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eHuang et al.\u003c\/strong\u003e studied stereotactic body radiation therapy (SBRT, very precise high-dose radiation) followed by pembrolizumab (an anti-PD-1 immunotherapy) in patients with metastatic NSCLC. Patients with immunologically \"cold\" tumors (tumors that immune cells largely ignore) had improved progression-free survival when SBRT came before immunotherapy. Levels of IFN-γ, IFN-α, and antigen processing and presentation gene sets were significantly higher in non-irradiated tumor sites after SBRT. Researchers also saw significant expansion of both new and pre-existing T-cell clones in the non-irradiated tumor (the abscopal site) and in the blood (the systemic response).\u003c\/p\u003e\n\n\u003ch2 id=\"trials\"\u003eWhat the Prospective Clinical Trials Show\u003c\/h2\u003e\n\n\u003cp\u003eMany prospective clinical trials (studies that follow patients forward in time) have tested radiotherapy plus immunotherapy in NSCLC patients. They vary widely in treatment combinations, size, and what they measure — a reflection of their different objectives.\u003c\/p\u003e\n\n\u003cp\u003eEndpoints across these trials have included progression-free survival (time without the cancer getting worse), overall survival, time to metastatic disease, local and regional recurrence, and safety. Endpoints have also included measures of systemic immune response such as the abscopal effect. Response assessment methods also differ. Some trials used RECIST v1.1; others used iRECIST to catch atypical patterns like pseudo-progression. Only two studies included out-of-field regression as an endpoint.\u003c\/p\u003e\n\n\u003cp\u003eHere is what the major trials looked like:\u003c\/p\u003e\n\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003eI-SABR\u003c\/strong\u003e — randomized phase II trial, \u003cstrong\u003e156 patients\u003c\/strong\u003e, nivolumab plus SABR (stereotactic ablative radiotherapy). Primary outcome was event-free survival.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eNCT03223155\u003c\/strong\u003e — randomized phase I trial, \u003cstrong\u003e37 patients\u003c\/strong\u003e, nivolumab plus ipilimumab plus SBRT. Primary outcomes were progression-free and overall survival. A modified version of RECIST v1.1 allowed both irradiated and nonirradiated metastases as target and nontarget lesions.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eASTEROID\u003c\/strong\u003e — randomized phase II trial (ongoing), \u003cstrong\u003e47 patients\u003c\/strong\u003e, durvalumab plus SBRT. Primary outcome was time to progression.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003ePACIFIC\u003c\/strong\u003e — randomized phase III trial, \u003cstrong\u003e713 patients\u003c\/strong\u003e, durvalumab plus chemoradiotherapy (CRT). Primary outcomes were progression-free and overall survival, assessed by RECIST v1.1.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eLUN14-179\u003c\/strong\u003e — single-arm phase II trial, \u003cstrong\u003e93 patients\u003c\/strong\u003e, pembrolizumab plus chemoradiotherapy. Primary outcome was time to metastatic disease.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eDETERRED\u003c\/strong\u003e — phase II trial, \u003cstrong\u003e40 patients\u003c\/strong\u003e, atezolizumab plus chemoradiotherapy. Primary outcomes were safety and tolerability.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eDOLPHIN\u003c\/strong\u003e — single-arm phase trial, \u003cstrong\u003e74 patients\u003c\/strong\u003e, durvalumab plus radiotherapy. Primary outcome was progression-free survival. Used RECIST v1.1 with no adjustments for abscopal effect.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003ePACIFIC-6\u003c\/strong\u003e — single-arm phase II trial, \u003cstrong\u003e117 patients\u003c\/strong\u003e, durvalumab plus chemoradiotherapy. Primary outcome was toxicity. Used RECIST v1.1 with no adjustments for abscopal effect.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eKEYNOTE-001\u003c\/strong\u003e — phase I trial, \u003cstrong\u003e98 patients\u003c\/strong\u003e, pembrolizumab plus radiotherapy. Primary outcomes were progression-free and overall survival. Used iRECIST 4.0.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eSICI\u003c\/strong\u003e — phase I trial, \u003cstrong\u003e15 patients\u003c\/strong\u003e, durvalumab plus tremelimumab plus SBRT. Primary outcome was safety. Used RECIST v1.1 with no adjustments.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eSWORD trial\u003c\/strong\u003e — phase II trial, \u003cstrong\u003e55 patients\u003c\/strong\u003e, sintilimab (an anti-PD1 antibody) plus SBRT plus granulocyte-macrophage colony-stimulating factor (GM-CSF). Primary outcomes included objective response rate and out-of-field response rate (ASR). The abscopal effect was a \u003cstrong\u003esecondary endpoint\u003c\/strong\u003e.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003ePembro-RT\u003c\/strong\u003e — prospective randomized phase I\/II trial, \u003cstrong\u003e148 patients\u003c\/strong\u003e, pembrolizumab plus radiotherapy. Primary outcomes included abscopal response rate, abscopal control rate, progression-free survival, and overall survival. RECIST v1.1 was applied by an independent reviewer, and \u003cstrong\u003ethe irradiated lesion was excluded from measurements\u003c\/strong\u003e. Pseudo-progression was not counted as progressive disease for the primary endpoint.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eSchoenfeld et al.\u003c\/strong\u003e — randomized phase II trial, \u003cstrong\u003e78 patients\u003c\/strong\u003e, durvalumab plus tremelimumab, alone or combined with low-dose or hypofractionated radiotherapy. Primary outcome was objective response rate. RECIST v1.1 was used with the irradiated lesion excluded. Local control within irradiated fields and abscopal response rates were not uniformly collected and therefore not reported.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eWelsh et al.\u003c\/strong\u003e — prospective randomized phase I\/II trial, \u003cstrong\u003e100 patients\u003c\/strong\u003e, SBRT plus pembrolizumab. Primary outcomes were toxicity and best out-of-field lesion response, assessed with immune-related response criteria.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eThis variability in how responses are measured underscores how hard it is to standardize outcomes in trials combining radiotherapy with immunotherapy. It also highlights how important it is to choose the right criteria — ones that capture both local treatment response and abscopal effects.\u003c\/p\u003e\n\n\u003ch2 id=\"discussion\"\u003eWhat This Evidence Means for Patients\u003c\/h2\u003e\n\n\u003cp\u003eThe big picture: the abscopal effect, once thought to be a rare curiosity, has become far more relevant in the era of combined treatments and immune checkpoint inhibition.\u003c\/p\u003e\n\n\u003cp\u003eSeveral trials in this review suggest that local irradiation may strengthen the body's systemic antitumor immune response when paired with immune checkpoint blockade. Radiotherapy induces immunogenic cell death and helps release tumor-associated antigens, which supports antigen presentation and activation of cytotoxic T cells. Combined with checkpoint inhibitors, this process may amplify systemic immune responses and make regression of distant, non-irradiated lesions more likely.\u003c\/p\u003e\n\n\u003cp\u003eSome trials tried to capture these systemic effects directly. The \u003cstrong\u003ePembro-RT trial excluded irradiated lesions from RECIST measurements\u003c\/strong\u003e to better evaluate systemic tumor responses. The \u003cstrong\u003eSWORD trial included out-of-field response rate as a secondary endpoint\u003c\/strong\u003e. In contrast, larger trials such as \u003cstrong\u003ePACIFIC focused mainly on survival outcomes\u003c\/strong\u003e and applied conventional RECIST criteria, which may underestimate how often abscopal responses occur.\u003c\/p\u003e\n\n\u003cp\u003eThe authors emphasize a critical point: the ability to detect and count abscopal responses depends entirely on the method used to assess tumor regression. Conventional RECIST v1.1 often fails to capture all out-of-field tumor regression, leading to under-recognition of systemic effects. iRECIST partially addresses these limitations, but not all immunotherapy trials use it. And unequivocal out-of-field regression is still not included as a standard criterion.\u003c\/p\u003e\n\n\u003ch2 id=\"definition\"\u003eThe Proposed Working Definition\u003c\/h2\u003e\n\n\u003cp\u003eBased on the evidence, the authors put forward a working definition of the abscopal effect in NSCLC. This is their core contribution.\u003c\/p\u003e\n\n\u003cp\u003eThe abscopal effect is defined as:\u003c\/p\u003e\n\n\u003col\u003e\n\u003cli\u003eRegression — either \u003cstrong\u003ecomplete or partial response by iRECIST criteria\u003c\/strong\u003e — of one or more non-irradiated lesions.\u003c\/li\u003e\n\u003cli\u003eThe lesions must be \u003cstrong\u003edistant from the primary treatment site\u003c\/strong\u003e.\u003c\/li\u003e\n\u003cli\u003eThe regression must occur \u003cstrong\u003eafter localized therapy, with or without systemic treatment\u003c\/strong\u003e.\u003c\/li\u003e\n\u003cli\u003eIt must be \u003cstrong\u003econfirmed by follow-up imaging within 4 to 8 weeks\u003c\/strong\u003e.\u003c\/li\u003e\n\u003c\/ol\u003e\n\n\u003cp\u003eEstablishing standardized terminology and assessment criteria will be essential for accurately identifying and integrating potential abscopal responses in future NSCLC research and clinical practice.\u003c\/p\u003e\n\n\u003ch2 id=\"limitations\"\u003eLimitations of the Current Evidence\u003c\/h2\u003e\n\n\u003cp\u003eThe authors are candid about the weaknesses in this field. Several limitations shape how confidently any conclusion can be drawn.\u003c\/p\u003e\n\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003eMost evidence comes from preclinical models and early-phase studies\u003c\/strong\u003e, not large randomized trials designed specifically to test the abscopal effect.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eStudy designs vary widely\u003c\/strong\u003e, including treatment combinations, endpoints, and methods of measuring response. This makes direct comparison across studies difficult.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eVery few trials were designed to evaluate out-of-field tumor regression.\u003c\/strong\u003e Most were built to measure survival or safety, not abscopal responses.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eAbscopal response data were often not uniformly collected\u003c\/strong\u003e — as in the Schoenfeld et al. trial, where abscopal response rates were not reported because the data were incomplete.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eEvidence for ablation-triggered abscopal effects is especially thin\u003c\/strong\u003e, resting largely on isolated case reports. The immune-modulating effects of ablation techniques remain poorly defined compared with radiotherapy.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eThe incidence of the abscopal effect in NSCLC is likely underestimated\u003c\/strong\u003e because standard response criteria do not capture it.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2 id=\"recommendations\"\u003eRecommendations and What Comes Next\u003c\/h2\u003e\n\n\u003cp\u003eThe authors offer a clear path forward. The central recommendation is adoption of a standardized definition and objective assessment criteria for the abscopal effect in NSCLC. Without them, real responses will keep slipping through the cracks.\u003c\/p\u003e\n\n\u003cp\u003eStandardization would allow researchers to:\u003c\/p\u003e\n\n\u003col\u003e\n\u003cli\u003eRecognize abscopal responses reliably instead of missing them.\u003c\/li\u003e\n\u003cli\u003eEvaluate them systematically across studies.\u003c\/li\u003e\n\u003cli\u003eCompare results between different trials and treatment combinations.\u003c\/li\u003e\n\u003cli\u003eIntegrate abscopal effects into real clinical decision-making.\u003c\/li\u003e\n\u003c\/ol\u003e\n\n\u003cp\u003eFor patients, the practical takeaway is this. If you receive radiation or ablation to one tumor and other tumors appear to shrink, that is a meaningful signal. That signal is worth discussing with your oncology team. Ask whether your imaging is being assessed with criteria that can capture out-of-field responses, such as iRECIST, and whether an abscopal response could explain what your scans show.\u003c\/p\u003e\n\n\u003cp\u003eThe authors also call for more research into the immune effects of ablation techniques, which lag behind radiotherapy in evidence. Their hope is that a shared vocabulary will let the field finally measure how often the abscopal effect happens — and use it to help more patients.\u003c\/p\u003e\n\n\u003c!-- ddn:faq:start --\u003e\n\u003ch2 id=\"ddn-faq\"\u003eFrequently Asked Questions\u003c\/h2\u003e\n\u003ch3\u003eWhat is the abscopal effect?\u003c\/h3\u003e\n\u003cp\u003eThe abscopal effect is when tumors that were never directly treated begin to shrink after treatment is delivered somewhere else in the body. It was first described in 1953 and has been seen in several cancers, including lung cancer. It is still considered uncommon, though experts think it may be underrecognized.\u003c\/p\u003e\n\u003ch3\u003eHow might radiation to one tumor shrink another?\u003c\/h3\u003e\n\u003cp\u003eRadiation can cause immunogenic cell death, releasing signals that activate dendritic cells and killer T cells. These T cells can travel through the bloodstream to distant, untreated tumors and attack cancer cells carrying the same proteins. Radiation can also suppress immune activity, which is one reason the effect is not more common.\u003c\/p\u003e\n\u003ch3\u003eCan ablation of a lung tumor trigger an abscopal effect?\u003c\/h3\u003e\n\u003cp\u003eAblation techniques such as cryoablation, microwave ablation, and pulsed electric field therapy can release tumor antigens and stimulate immune responses. In one case report, a 69-year-old man with advanced squamous NSCLC had microwave ablation to his primary lung tumor, and untreated mediastinal lymph nodes later shrank. However, evidence for ablation-triggered abscopal effects remains limited to isolated case reports.\u003c\/p\u003e\n\u003ch3\u003eWhy might my scans not show an abscopal response?\u003c\/h3\u003e\n\u003cp\u003eStandard response criteria called RECIST v1.1 focus on selected target lesions and may not capture shrinkage in non-target or non-irradiated tumors. iRECIST was designed for immunotherapy and can account for pseudo-progression, but it still does not systematically record out-of-field regression. This means abscopal responses may be missed on routine assessments.\u003c\/p\u003e\n\u003ch3\u003eWhat is the proposed definition of the abscopal effect in NSCLC?\u003c\/h3\u003e\n\u003cp\u003eThe authors propose defining it as regression—complete or partial response by iRECIST—of one or more non-irradiated lesions distant from the treated site. It must occur after localized therapy, with or without systemic treatment, and be confirmed by follow-up imaging within 4 to 8 weeks. This definition aims to standardize how the effect is identified.\u003c\/p\u003e\n\u003ch3\u003eDoes combining radiation with immunotherapy increase the chance of an abscopal effect?\u003c\/h3\u003e\n\u003cp\u003ePreclinical and early clinical studies suggest that adding an immune checkpoint inhibitor to radiation may amplify the abscopal effect. For example, in a study by Huang et al., patients with metastatic NSCLC who received stereotactic body radiation therapy before pembrolizumab showed immune changes in non-irradiated tumors. However, prospective trials vary widely in design and how they measure responses.\u003c\/p\u003e\n\u003ch3\u003eIf I receive radiation or ablation and other tumors shrink, what should I do?\u003c\/h3\u003e\n\u003cp\u003eThat is a meaningful signal worth discussing with your oncology team. Ask whether your imaging is being assessed with criteria that can capture out-of-field responses, such as iRECIST, and whether an abscopal response could explain what your scans show. The authors recommend standardized assessment to ensure such responses are recognized.\u003c\/p\u003e\n\u003ch3\u003eIf radiation or ablation to one lung tumor shrinks other untreated tumors, when should I seek a second opinion on my scans?\u003c\/h3\u003e\n\u003cp\u003eIf you receive radiation or ablation to one tumor and other, untreated tumors appear to shrink, that is a meaningful signal worth discussing with your oncology team. Standard RECIST v1.1 criteria often fail to capture regression in non-irradiated lesions, so an abscopal response may go unrecognized. Ask whether your imaging is assessed with criteria such as iRECIST that can capture out-of-field responses, and whether an abscopal response could explain your scans. A second opinion can review whether your imaging was measured with criteria able to detect these responses. Diagnostic Detectives Network provides independent expert second opinions.\u003c\/p\u003e\n\u003c!-- ddn:faq:end --\u003e\n\n\u003ch2 id=\"source\"\u003eSource Information\u003c\/h2\u003e\n\n\u003cp\u003e\u003cstrong\u003eOriginal article title:\u003c\/strong\u003e Defining the abscopal effect in non-small cell lung cancer in the era of immunotherapy and lung ablation treatment: a narrative review.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAuthors:\u003c\/strong\u003e Illaa Smesseim, Phillip N. Perez, Abraham Chachoua, Benjamin T. Cooper, and Daniel H. Sterman\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAuthor affiliations:\u003c\/strong\u003e Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands; Department of Pulmonary Diseases, Leiden University Medical Center, Leiden, Netherlands; NYU Pulmonary Oncology Research Team (NYU PORT), Division of Pulmonary, Critical Care \u0026amp; Sleep Medicine, Department of Medicine, NYU Langone Health, New York, NY, United States; Department of Medicine, NYU Grossman School of Medicine, New York, NY, United States; Department of Radiation Oncology, NYU Langone Health, New York, NY, United States\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eJournal:\u003c\/strong\u003e Frontiers in Medicine, volume 13, article 1804711\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eArticle type:\u003c\/strong\u003e Review\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003ePublication date:\u003c\/strong\u003e Published 23 April 2026 (received 05 February 2026; revised 25 March 2026; accepted 30 March 2026)\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eDOI:\u003c\/strong\u003e 10.3389\/fmed.2026.1804711\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eNote:\u003c\/strong\u003e This patient-friendly article is based on peer-reviewed research. It is intended for educational purposes and should not replace personalized medical advice from your own oncology team. If you have questions about your treatment or imaging results, speak with your treating physician.\u003c\/p\u003e","brand":"DiagnosticDetectives.Com","offers":[{"title":"Default Title","offer_id":47576871239836,"sku":null,"price":0.0,"currency_code":"KRW","in_stock":true}],"url":"https:\/\/diagnosticdetectives.kr\/products\/the-abscopal-effect-in-non-small-cell-lung-cancer-when-treating-one-tumor-shrinks-tumors-elsewhere-in-the-body","provider":"DiagnosticDetectives.Com","version":"1.0","type":"link"}