Gastric Cancer Radiation Management: Evidence-Based Clinical Summary

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RxDrug of choiceFluorouracil 425 mg/m²/day IV bolus + leucovorin 20 mg/m²/day on days 1-5, given concurrently with RT weeks 1, 5, and 9 (INT-0116 regimen).

AltAlternativesCapecitabine 825 mg/m² PO BID on days of RT (ARTIST regimen); FOLFOX (oxaliplatin + infusional 5-FU) for definitive CRT.

⊘AvoidActive inflammatory bowel disease, prior abdominal RT exceeding total tolerance, pregnancy, inability to tolerate breath-hold (if needed), R2 resection after D2 dissection (no benefit).

DxTest of choiceContrast-enhanced CT of chest, abdomen, pelvis for staging and planning; 4D CT simulation for motion management.

ScKey scoreLocoregional failure nomogram after D2 surgery: includes pT category (3-4 vs 1-2) and lymph node ratio (>25% vs ≤25%); AUC 0.79.

→When to referRefer to radiation oncology for any patient with resected gastric cancer after D0/D1 dissection, unresectable local disease, or symptomatic bleeding/pain/obstruction. Refer to surgical oncology for anastomotic stricture, pancreatic fistula, or duodenal stump fistula. Refer to palliative care for advanced disease.

Adjuvant chemoradiotherapy (45 Gy + FU/leucovorin) is indicated after D0/D1 R0 resection; after D2 R0 resection, RT does not improve outcomes. For unresectable disease, definitive CRT (50.4 Gy) or palliative RT (30 Gy/10 fx) provides effective symptom control. IMRT with breath-hold techniques reduces toxicity.

Radiation management for [[gastric cancer]] spans curative-intent adjuvant treatment to palliation. Indications depend on surgery extent, nodal dissection, and chemotherapy. Key trials include INT-0116, ARTIST, CRITICS, and TOPGEAR. Modern techniques use IMRT/VMAT with careful OAR sparing. Brachytherapy offers salvage for limited metastases. Concurrent chemoradiation with fluoropyrimidine is standard after suboptimal dissection.

Overview and Recommendations

Background

•Radiation therapy (RT) for gastric cancer targets locoregional control, addressing the dominant failure pattern after limited nodal dissection. The landmark INT-0116 trial (1998) established postoperative chemoradiotherapy (45 Gy with concurrent fluorouracil and leucovorin) as a standard after R0 resection with D0/D1 lymphadenectomy, reducing locoregional relapse and improving overall survival (HR 1.32).
•The benefit of adjuvant RT is context-dependent: after adequate D2 gastrectomy, the addition of radiotherapy to modern chemotherapy (e.g., SOX) does not improve disease-free survival (ARTIST 2). Subgroup analyses suggest possible benefit in node-positive, intestinal-type tumors, but routine use is not recommended.
•For patients with locally advanced, unresectable gastric cancer, definitive chemoradiotherapy (45-50.4 Gy) provides durable disease control, with clinical complete response rates of 12-45% and median overall survival of 11-26 months. Palliative RT (30 Gy/10 fx) effectively controls bleeding (60-90%), pain (45-100%), and obstruction (53-100%) with <5% grade 3 GI toxicity.
•Preoperative chemoradiotherapy increases pathological complete response (pCR) rates (17% vs 8% in TOPGEAR) but does not improve overall survival compared to perioperative chemotherapy alone. It is conditionally recommended for borderline resectable tumors or patients who cannot tolerate perioperative chemotherapy.
•Brachytherapy (interstitial HDR or permanent 125I seeds) offers a minimally invasive option for limited-volume metastases (<3 cm, PTV <45 cm³) or locoregional recurrence after gastrectomy, achieving local control of 89% and 50% complete response, respectively, with low toxicity.
•The paradigm shift from 3D-CRT to IMRT/VMAT, combined with breath-hold techniques and daily IGRT, has improved target coverage and reduced toxicity to kidneys, liver, and bowel. Renal function is a key concern, with left kidney dose constraints (mean ≤13 Gy, V20 ≤13%) critical to prevent functional impairment.

Evaluation

•Suspect the need for gastric cancer RT in any patient with resected stage IB-III disease after D0/D1 lymphadenectomy, unresectable local disease, or symptomatic bleeding/pain/obstruction from advanced disease.
•Review the operative report to determine the extent of lymph node dissection (D0/D1 vs D2) and margin status (R0/R1/R2), this is the single most important factor guiding RT indication.
•Assess patient fitness for concurrent chemotherapy: ECOG performance status 0-2, adequate renal function (eGFR ≥30 mL/min), hepatic function, and marrow reserve (ANC ≥1.5, platelets ≥100).
•Obtain a baseline contrast-enhanced CT of the chest, abdomen, and pelvis for staging and treatment planning. PET/CT may be considered for detection of occult metastases, especially in the preoperative setting.
•For adjuvant RT after D2 dissection, identify high-risk features: pT3-4, lymph node ratio >25%, or extraperigastric nodal involvement. A nomogram (AUC 0.79) can predict locoregional failure risk and guide patient selection.
•For definitive RT, perform endoscopic ultrasound (EUS) for T and N staging, and rule out distant metastases with imaging. Consider diagnostic laparoscopy to exclude peritoneal dissemination before high-dose RT.
•For palliative RT, document the target symptom (bleeding, pain, obstruction) and its severity. For bleeding, confirm active bleeding source via endoscopy and consider prior embolization if RT is not immediately available.
•Assess prior radiation exposure: if the patient has received previous abdominal RT, obtain treatment records and calculate cumulative dose to OARs, especially kidneys, spinal cord, and bowel.
•Evaluate for contraindications: active inflammatory bowel disease, pregnancy, prior radiation to the same field exceeding tolerance, or inability to tolerate immobilization (e.g., breath-hold).
•Obtain a 4D CT simulation with the patient in supine position, arms up, with a custom immobilization device. Use oral contrast to delineate the stomach body and tumor bed. Consider breath-hold planning if respiratory motion >1 cm in the SI direction.

Management

•For adjuvant RT after D0/D1 R0 resection: prescribe 45 Gy in 25 fractions (1.8 Gy/fx) to the tumor bed, anastomosis, duodenal stump, and regional lymph nodes (perigastric stations 1-6, celiac 9, splenic 10-11, hepatoduodenal 12, pancreaticoduodenal 13, para-aortic 16).
•Deliver concurrent chemotherapy: fluorouracil 425 mg/m²/day IV bolus on days 1-5 and leucovorin 20 mg/m²/day IV bolus on days 1-5, repeated at weeks 1, 5, and 9 (INT-0116 regimen). Alternatively, capecitabine 825 mg/m² PO BID on days of RT (ARTIST regimen).
•After D2 R0 resection, do not routinely add RT to adjuvant chemotherapy. For patients with high-risk features (pT3-4, N2+, extraperigastric LN), consider a shared decision-making discussion; if RT is offered, target the para-aortic basin (stations 16a/16b) and omit perigastric stations 1-6 and splenic hilum.
•For unresectable nonmetastatic disease: prescribe 50.4 Gy in 28 fractions (1.8 Gy/fx) with concurrent fluoropyrimidine (e.g., capecitabine 825 mg/m² BID) or FOLFOX. Consider induction chemotherapy (2 cycles of SOX or FOLFOX) before CRT.
•For palliative RT for bleeding: prescribe 30 Gy in 10 fractions (3 Gy/fx). Symptom relief typically occurs within 2-10 days. For pain or obstruction, the same regimen is effective; for obstruction, consider a higher dose (39 Gy in 13 fx or 40 Gy in 20 fx) if tolerance permits.
•Use IMRT or VMAT preferentially to reduce dose to kidneys, liver, and bowel. Key OAR constraints: liver mean ≤16 Gy, V30 ≤21%; right kidney mean ≤9 Gy, V20 ≤9%; left kidney mean ≤13 Gy, V20 ≤13%; heart V40 ≤17%; bowel mean ≤11 Gy, V40 ≤6%; spinal cord max ≤33 Gy.
•Implement respiratory motion management: use 4D CT simulation to define the ITV. If breath-hold is feasible, use deep inspiration breath-hold (DIBH) to reduce SI motion to ~2 mm, allowing margin reduction and potential dose escalation to 54 Gy.
•For patients with preexisting nephropathy (eGFR <60 mL/min), prioritize IMRT/VMAT and consider referral to a center with proton therapy to further reduce renal dose.
•Monitor during treatment: weekly CBC, CMP, and symptom assessment. Grade 3 GI toxicity (nausea, vomiting, diarrhea) occurs in 0-31% of definitive cases; manage with antiemetics (ondansetron 8 mg PO TID, prochlorperazine 10 mg PO QID), loperamide, and IV fluids as needed.
•Do not use multiagent concurrent chemotherapy (e.g., ECF), CALGB 80101 showed no survival benefit over single-agent fluoropyrimidine.
•Do not add postoperative RT after preoperative chemotherapy and D2 surgery (CRITICS trial showed harm, HR 1.62).
•For brachytherapy candidates: select patients with ≤5 metastases, each <3 cm, PTV <45 cm³, and good performance status. For liver metastases, use image-guided HDR interstitial brachytherapy (single fraction, 15-20 Gy). For locoregional recurrence, use CT-guided 125I seed implantation (100-160 Gy minimal peripheral dose).
•After RT, monitor for late toxicity: anastomotic stricture (5.9%), dysphagia (28.3% with right esophagojejunostomy, 12.5% with left), and pancreatic fistula. Refer to surgical oncology for management of strictures (endoscopic dilation) and nutritional support if needed.
•Refer to palliative care early for symptom management and advanced care planning, especially for patients with inoperable disease. Early integration reduces emergency visits and hospitalizations.
•Discharge criteria from RT: completion of prescribed course, stable vital signs, adequate oral intake, controlled pain, and no evidence of acute grade ≥3 toxicity. Follow up in 4-6 weeks with imaging and symptom assessment.

Board Review — High Yield

•INT-0116, Landmark trial establishing adjuvant chemoradiotherapy (45 Gy + FU/leucovorin) after D0/D1 R0 resection for T3-4 or N+ gastric cancer; HR for OS 1.32, HR for RFS 1.51.
•ARTIST 2, After D2 resection, adding RT to SOX does not improve 3-year DFS compared to SOX alone (72.8% vs 74.3%; HR 0.971); modern chemotherapy alone is sufficient.
•CRITICS trial, After preoperative chemotherapy and D2 surgery, postoperative chemoradiotherapy worsened OS compared to chemotherapy alone (per-protocol 5-year OS 45.5% vs 57.9%; HR 1.62).
•TOPGEAR, Preoperative CRT (45 Gy) increases pCR (17% vs 8%) but does not improve OS over perioperative chemotherapy alone.
•Palliative RT dose, 30 Gy in 10 fractions is the standard for bleeding, pain, and obstruction; response rates: bleeding 60-90%, pain 45-100%, obstruction 53-100%.
•IMRT benefit, Meta-analysis shows IMRT improves 3-year local control over 3D-CRT with no significant difference in OS or toxicity.
•Brachytherapy selection, Lesion size <3 cm and PTV <45 cm³ are critical predictors of complete response; HDR iBT for metastases, 125I seeds for locoregional recurrence.
•Para-aortic station 16, Most common site of locoregional failure after D2 dissection; should be included in CTV for high-risk patients.
•Left kidney dose, Mean ≤13 Gy, V20 ≤13% are critical constraints to prevent functional impairment; use IMRT or breath-hold to achieve.
•CALGB 80101, Multiagent concurrent chemotherapy (ECF) does not improve survival over single-agent FU when combined with RT; use single-agent FU.

Deep Dive — Evidence Details

Indications by Stage

▸Adjuvant chemoradiation after D0/D1 dissection improves OS (INT-0116).
▸No benefit after D2 dissection; definitive chemoradiation for unresectable disease.

HY High Yield: Adjuvant chemoradiation is not recommended after D2, R0 resection [19].

Radiation therapy for is indicated across the disease spectrum. Adjuvant chemoradiotherapy is indicated after suboptimal nodal dissection (D0/D1) based on INT-0116 (45 Gy with concurrent 5-FU/leucovorin, HR for OS 1.32) ^[2]^A1b. After adequate D2 dissection, the ARTIST trial ^[5]^A1b and a Chinese phase III trial ^[19]^A1b showed no DFS benefit, so it is not recommended. Preoperative chemoradiation is conditionally recommended for borderline resectable tumors or when patients cannot tolerate perioperative chemotherapy; TOPGEAR showed no OS benefit but increased pCR (17% vs 8%) ^[11]^B2b. For locally advanced unresectable disease, definitive chemoradiotherapy (45-50.4 Gy) provides durable control (median OS 11-26.4 months) ^[17]^A1a. For palliation, high-dose RT (e.g., 30 Gy/10 fractions) achieves bleeding response rates 60-90% ^[17]^A1a. Pearl: For patients with D2-resected gastric cancer, the addition of radiotherapy to adjuvant chemotherapy does not improve survival; its role is limited to cases of suboptimal nodal dissection (D0/D1) or R1/R2 resection, where it remains a conditionally recommended option.

Key Trials Shaping Indications for Radiotherapy in Gastric Cancer

Trial	Population	Intervention	Key Finding	Implication for Indication
INT-0116 ^[2]^A1b	R0, T3-4/N+, <D2 dissection	Postop CRT vs observation	OS HR 1.32 (95% CI 1.10-1.60)	Postop CRT indicated for <D2
ARTIST ^[3]^A1b^[5]^A1b	D2, R0, all stages	XP vs XPRT	DFS similar; subset benefit in node+	Not routine after D2
CRITICS ^[1]^A1b^[9]^A1b	Preop chemo, D1+ dissection	Postop chemo vs CRT	OS HR 1.01 (95% CI 0.84-1.22)	No benefit for postop CRT after preop chemo
TOPGEAR ^[11]^B2b	Resectable, perioperative chemo	Preop CRT + chemo vs chemo alone	OS HR 1.05 (95% CI 0.83-1.31)	Preop CRT not superior to chemo alone
Chinese D2 trial ^[19]^A1b	D2, T4/N+, R0	SOX vs SOX+RT (50.4 Gy)	3y DFS 70.5% vs 69.3% (HR 0.98)	No benefit for adjuvant RT after D2
Definitive RT ^[17]^A1a	Inoperable, nonmetastatic	45-50.4 Gy/25-28# with chemo	mOS 11-26.4 mo, cCR 12-45%	Definitive CRT offers durable control
Palliative RT ^[17]^A1a	Advanced/metastatic	30 Gy/10# (most common)	Bleeding RR 60-90%, pain RR 46-100%	Effective palliation for bleeding, pain, obstruction

External Beam Radiotherapy (EBRT)

▸Definitive and high-dose palliative radiotherapy were defined in the 2024 systematic review using BED10 thresholds of >45 Gy and >30 Gy, respectively. [17]
▸Selected inoperable or unresectable nonmetastatic patients have been treated with peri-irradiation chemotherapy plus IMRT to 50.4 Gy and concurrent weekly docetaxel. [28]
▸Postoperative randomized and prospective studies commonly used 45 Gy in 25 fractions with concurrent fluoropyrimidine-based therapy after D2 or D1/D2 surgery. [21,23,24,30]
▸IMRT, image guidance, breath-hold, and three-dimensional planning can improve dose conformity or organ sparing, but clinical superiority over 3D-CRT is not consistently proven. [31,32,36,125]
▸Renal protection, nutritional assessment, and management of acute gastrointestinal toxicity are essential components of gastric EBRT. [34,122,124,126]

! Warning: Do not extrapolate oesophageal definitive chemoradiotherapy standards directly to gastric cancer: gastric exclusive-chemoradiation studies have used heterogeneous doses and target definitions, and a universally accepted protocol has not been established. [17,27]

CP Clinical Pearl: Before gastric EBRT, document nutritional risk, review renal function, and use image-guided conformal planning when feasible; these measures address common toxicity and organ-at-risk concerns. [31,34,122,126]

Clinical role and treatment intent

EBRT has a selective role in gastric adenocarcinoma. For resectable disease, contemporary evidence and expert reviews describe radiotherapy indications as limited, whereas EBRT remains useful for palliation of bleeding or dysphagia and may be considered in selected postoperative high-risk patients. ^[26]^A1c Exclusive chemoradiotherapy for localized or unresectable gastric cancer has historically lacked a consensual dose protocol and target-volume definition. ^[27]^A1c

For inoperable or medically unresectable nonmetastatic gastric cancer, definitive or high-dose palliative EBRT is an area of renewed interest. A 2024 systematic review defined definitive treatment as nonmetastatic disease treated with a BED10 >45 Gy and high-dose palliation as symptom or local-control treatment using a minimum BED10 >30 Gy. ^[17]^A1a The review specifically examined whether evidence supports moving beyond the traditional practice of reactive, low-dose radiotherapy, commonly delivered for symptoms such as bleeding. ^[17]^A1a Evidence for definitive treatment should therefore be distinguished from evidence for short-course or conventional palliative haemostatic treatment. ^[17]^A1a

Definitive EBRT for inoperable or unresectable disease

Prospective phase 2 evidence supports the feasibility of combining systemic therapy with definitive-intent EBRT in selected patients who cannot undergo surgery because of comorbidity, refusal, or unresectability. In one multicentre study, patients received peri-irradiation docetaxel, cisplatin, and continuous-infusion fluorouracil, followed by IMRT to 50.4 Gy with concurrent weekly docetaxel, and subsequent chemotherapy. ^[28]^B2b This regimen was designed for nonmetastatic inoperable or unresectable gastric carcinoma; the study’s primary purpose was to assess efficacy and feasibility rather than establish a randomized standard. ^[28]^B2b

The evidence base remains heterogeneous, and older reviews reported conflicting results without clinical evidence favouring one exclusive-chemoradiation dose schedule or target-volume definition. ^[27]^A1c Accordingly, definitive EBRT should generally be individualized through multidisciplinary review, considering performance status, comorbidity, disease extent, nutritional status, chemotherapy tolerance, and the possibility of occult metastatic disease. ^[17]^A1a^[27]^A1c^[28]^B2b

Postoperative chemoradiotherapy

Postoperative EBRT is most relevant after gastrectomy in patients with substantial locoregional-risk features, including advanced T stage, nodal involvement, or concerns regarding local control. Randomized studies after D2 dissection have evaluated chemotherapy alone against postoperative chemoradiotherapy. In a 2012 multicentre randomized trial, adjuvant IMRT with chemotherapy was compared with chemotherapy alone; the chemoradiotherapy regimen used fluorouracil and leucovorin with 45 Gy in 25 fractions over 5 weeks. ^[23]^A1b A separate randomized study of patients with T3/T4 and/or node-positive disease after D1/D2 surgery used concurrent chemoradiotherapy with 45 Gy in 25 fractions, alongside continuous 5-fluorouracil and leucovorin. ^[24]^A1b

A newer prospective randomized study specifically investigated patients after D2 resection and compared eight cycles of SOX chemotherapy with postoperative CRT. In the CRT arm, radiotherapy was delivered using IMRT at 45 Gy in 25 fractions of 1.8 Gy over 5 weeks, concurrently with S-1, after 4–6 cycles of SOX. ^[21]^A1b This trial was designed to identify high-risk patients who may benefit from adjuvant radiation and to evaluate long-term outcomes; its findings should be interpreted in the context of surgical quality, pathological risk, systemic regimen, and regional practice. ^[21]^A1b

Other prospective evidence has examined postoperative concurrent treatment after R0 gastrectomy with D2 lymphadenectomy. A phase 2 study used FOLFOX with concurrent 3D-CRT or IMRT to 50.4 Gy in 28 fractions, with chemotherapy administered before and after chemoradiotherapy. ^[29]^B2b A prospective feasibility study in high-risk stage II–III patients treated after gastrectomy and D2 lymphadenectomy used IMRT to 45 Gy at 1.8 Gy per fraction with continuous-infusion 5-fluorouracil. ^[30]^C4

Planning technique and organ protection

IMRT provides improved dose conformity compared with 3D-CRT and may reduce normal-tissue exposure or facilitate dose escalation, although comparative clinical benefit is not uniformly established. ^[36]^B2a A systematic review and meta-analysis compared IMRT with 3D-CRT for survival, disease-free survival, local control, and toxicity, reflecting continuing uncertainty about whether dosimetric advantages consistently translate into superior oncologic outcomes. ^[36]^B2a An earlier planning analysis found only limited advantages of IMRT over 3D-CRT in the adjuvant setting, despite the potential for improved conformality. ^[32]^B2b

Modern planning should account for respiratory motion, setup uncertainty, and the proximity of the kidneys, liver, bowel, and spinal cord. A dosimetric study found that breath-hold with online image guidance can reduce target motion and setup-related margins compared with free breathing, potentially improving organ sparing. ^[31]^B2b CT-based three-dimensional planning also demonstrated dosimetric and clinical differences compared with conventional two-dimensional planning in postoperative CRT. ^[125] VMAT planning produced target coverage comparable with 3D-CRT and IMRT while improving dose conformity in a small dosimetric comparison, but the analysis was retrospective and included only 12 patients. ^[33]^A1b

Kidney protection is particularly important. Observational data comparing AP–PA fields, 3D-CRT, and IMRT after postoperative CRT found that IMRT can limit late nephrotoxicity. ^[126]^C Functional MRI data further suggested dose-dependent renal changes after adjuvant radiochemotherapy and described image-guided IMRT as permitting kidney sparing while maintaining target coverage. ^[34]^B2b Proton therapy, heavy-ion therapy, and helical tomotherapy have been studied mainly in small, nonrandomized series; the evidence map identified substantial gaps in comparative efficacy and toxicity evidence. ^[121]

Toxicity, nutrition, and supportive care

Acute gastrointestinal toxicity is a principal limitation of gastric EBRT, particularly when combined with chemotherapy. ^[30]^C4 IMRT was associated with reduced acute toxicity compared with 3D-CRT in a retrospective cohort of patients receiving preoperative chemoradiation, although the nonrandomized design limits causal inference. ^[124]^C Nutritional status should be assessed before and during treatment because weight loss, low body mass index, hypoalbuminemia, and elevated nutritional-risk scores were common among patients receiving gastric radiotherapy and were investigated as predictors of treatment-related adverse events. ^[122]

Practical synthesis

EBRT should not be regarded as routine for every resectable gastric cancer patient. ^[26]^A1c Its strongest contemporary applications are selected postoperative high-risk disease, definitive chemoradiation for medically inoperable or unresectable nonmetastatic disease, and symptom-directed palliation, especially for bleeding or dysphagia. ^[17]^A1a^[26]^A1c^[28]^B2b Treatment should use image-guided conformal planning where available, prioritize kidney and bowel protection, and integrate nutritional and systemic-therapy assessment. ^[31]^B2b^[34]^B2b^[36]^B2a^[122]^[126]^C

EBRT applications and evidence

Clinical setting	Typical evidence-based approach or dose	Evidence and considerations
Definitive treatment for inoperable/unresectable nonmetastatic disease	IMRT with concurrent chemotherapy; phase 2 regimen used 50.4 Gy	Feasible in selected patients, but not established as a universal standard. ^[17]^A1a^[28]^B2b
Postoperative high-risk disease after D2 resection	IMRT 45 Gy/25 fractions with concurrent S-1 or other fluoropyrimidine-based therapy	Evaluated in prospective randomized studies against chemotherapy alone. ^[21]^A1b^[23]^A1b
Postoperative disease after D1/D2 surgery	45 Gy/25 fractions with fluorouracil/leucovorin	Randomized prospective evidence exists, with interpretation dependent on surgical and pathological risk. ^[24]^A1b
Postoperative R0/D2 treatment with FOLFOX	50.4 Gy/28 fractions using 3D-CRT or IMRT	Investigated in a phase 2 study with peri-radiotherapy FOLFOX. ^[29]^B2b
Palliation	Dose and fractionation individualized; high-dose palliation defined as BED10 >30 Gy	Particularly relevant for bleeding or dysphagia; evidence remains heterogeneous. ^[17]^A1a^[26]^A1c

Brachytherapy

▸Gastric-cancer brachytherapy evidence is limited to retrospective clinical series and a xenograft study, without a randomized trial or validated consensus dose standard in the supplied references [43][47][48].
▸Image-guided high-dose-rate interstitial brachytherapy used temporary iridium-192 in a single fraction for selected metastatic gastric adenocarcinoma lesions after palliative chemotherapy [43].
▸CT-guided permanent iodine-125 seed implantation was reported in 28 patients with locoregional recurrent gastric cancer, using 15–75 seeds and a minimal peripheral dose of 100–160 Gy [47].
▸Iodine-125 seed irradiation produced preclinical biological effects in SGC-7901 gastric-cancer xenografts, but animal data do not define human efficacy or dosing [48].
▸Brachytherapy should be regarded as a carefully selected local or salvage option rather than routine treatment for resectable gastric cancer [43][47][48].

! Warning: The reported 100–160 Gy iodine-125 implant dose is specific to one retrospective recurrent-disease series and is not a universal gastric-cancer brachytherapy prescription [47].

CP Clinical Pearl: The strongest clinical rationale in the supplied evidence is image-guided, multidisciplinary treatment of carefully selected recurrent or metastatic lesions after systemic therapy, rather than routine primary-gastric irradiation [43][47].

Scope and rationale

Brachytherapy is a localized radiation technique in which a radioactive source is positioned within or immediately adjacent to the target lesion. In the gastric-cancer literature represented here, its clinical use is described primarily for unresectable or recurrent disease and for selected metastatic lesions rather than as an established routine component of curative treatment for newly diagnosed, resectable gastric cancer ^[43]^C4^[47]^D5^[48]^D5. The available gastric-cancer evidence is limited to retrospective clinical series and preclinical experimentation; no randomized gastric-cancer trial or consensus dose standard is identified in these references ^[43]^C4^[47]^D5^[48]^D5.

Image-guided interstitial brachytherapy for metastases

Omari et al. retrospectively evaluated image-guided high-dose-rate interstitial brachytherapy (iBT) as second-line or salvage treatment for metastatic gastric adenocarcinoma ^[43]^C4. Twelve patients with a cumulative total of 36 metastases received treatment between 2010 and 2016; the lesions comprised 29 hepatic, 5 lymph-node, and 2 pancreatic metastases ^[43]^C4. Every patient had received palliative chemotherapy before iBT, indicating that the technique was used in a previously treated, non-curative clinical setting ^[43]^C4.

The procedure involved temporary intratumoral placement of an iridium-192 source and administration of a single fraction, with the treatment objective of tumor-cell eradication ^[43]^C4. Clinical and radiologic assessments were performed during follow-up, although this small retrospective study should be interpreted as feasibility and early-effectiveness evidence rather than proof of comparative survival benefit ^[43]^C4. The study population was highly selected, and the reference does not establish iBT as a replacement for systemic therapy, surgery, or other ablative modalities ^[43]^C4.

CT-guided permanent seed implantation for locoregional recurrence

CT-guided permanent brachytherapy has been investigated for locoregionally recurrent gastric cancer, a setting in which recurrence was described as typically not amenable to surgical removal ^[47]^D5. In a retrospective series, a multidisciplinary team selected 28 patients for treatment and reviewed patient characteristics, implantation parameters, short-term effects, and survival outcomes ^[47]^D5.

The technique used permanent iodine-125 seed implantation, with 15–75 seeds per patient and a reported minimal peripheral dose of 100–160 Gy ^[47]^D5. These dose values describe the prescribed implant parameters in this series and should not be interpreted as a universally validated gastric-cancer dose recommendation ^[47]^D5. CT guidance and multidisciplinary selection were central to the reported approach, supporting consideration of permanent seed implantation only in carefully assessed patients with localized recurrent disease ^[47]^D5.

The reference supports feasibility and clinical investigation of CT-guided permanent brachytherapy, but the retrospective design, limited sample size, and absence of a comparator restrict conclusions regarding efficacy, overall survival, quality of life, or superiority over systemic treatment or external-beam radiotherapy ^[47]^D5.

Preclinical evidence and biological effects

A xenograft study examined continuous, low-energy iodine-125 irradiation in human gastric-cancer models ^[48]^D5. Sixty mice bearing SGC-7901 gastric-cancer xenografts were randomized to sham-seed control or iodine-125 treatment, with 30 animals in each group; treatment seeds had an activity of 0.6 mCi, whereas control seeds had 0 mCi ^[48]^D5. At 28 days after irradiation, the investigators assessed apoptosis, cell-cycle distribution, NF-κB and VEGF expression, and tumor growth ^[48]^D5.

This experiment provides mechanistic and proof-of-concept support for iodine-125 seed irradiation as a potential supplementary treatment for unresectable advanced gastric cancer, but animal findings cannot establish clinical efficacy, safety, or an appropriate human implantation dose ^[48]^D5. The study should therefore be used to support biological plausibility rather than treatment selection ^[48]^D5.

Evidence boundaries and related techniques

Brachytherapy combined with external radiotherapy was reported for large desmoid tumors in patients with Gardner syndrome, but that cohort did not concern gastric cancer and should not be extrapolated as evidence for gastric-cancer brachytherapy ^[45]^B2b. Similarly, the cited review of hyperthermic intraperitoneal chemotherapy concerns peritoneal carcinomatosis from gastric cancer but evaluates HIPEC, not brachytherapy ^[41]^A1a. Reviews of VEGFR-targeted drugs and reports on laparoscopic gastrectomy do not provide brachytherapy evidence ^[40]^B2a^[42]^C4. Palliative-management guidance emphasizes symptom-directed, least-invasive care for advanced gastric or esophageal cancer, but it does not establish brachytherapy-specific indications or doses ^[46]^D5.

Practical interpretation

Within the evidence supplied, brachytherapy may be considered an investigational or highly selected local treatment for unresectable locoregional recurrence, and as salvage treatment for selected metastatic lesions after systemic therapy ^[43]^C4^[47]^D5. Treatment should be delivered through multidisciplinary evaluation with image guidance and individualized dosimetry, while counseling patients that the supporting evidence is retrospective, small-scale, and noncomparative ^[43]^C4^[47]^D5.

Clinical and preclinical brachytherapy evidence

Setting	Technique and dose information	Evidence base	Reference
Metastatic gastric adenocarcinoma	Image-guided high-dose-rate interstitial brachytherapy; temporary iridium-192; single fraction; 36 lesions in 12 patients	Retrospective second-line/salvage series; all patients previously received palliative chemotherapy	^[43]^C4
Locoregional recurrent gastric cancer	CT-guided permanent iodine-125 seeds; 15–75 seeds per patient; minimal peripheral dose 100–160 Gy	Retrospective series of 28 multidisciplinary-selected patients	^[47]^D5
Gastric-cancer xenografts	Continuous low-energy iodine-125 irradiation; 0.6 mCi treatment seeds; assessment at 28 days	Randomized mouse xenograft experiment using 60 mice	^[48]^D5

Concurrent Chemoradiation

▸Randomized phase III evidence directly compares preoperative CRT with perioperative SOX chemotherapy in locally advanced gastric or GEJ adenocarcinoma, but numerical outcomes are not available in the supplied abstract. [20]
▸Postoperative CRT trials after D2 gastrectomy use modern SOX-based chemotherapy and investigate disease-free survival, particularly in T4 or node-positive disease. [19,21]
▸The clearest reported postoperative RT schedule is **45 Gy in 25 fractions of 1.8 Gy**, delivered over five weeks with concurrent S-1. [21]
▸Neoadjuvant CRT plus immune-checkpoint inhibition is supported by a 2026 systematic review and meta-analysis as an active clinical research strategy, not as an automatically established standard. [16]
▸Pembrolizumab plus perioperative chemotherapy improved pathologic complete response by **10.9 percentage points** in KEYNOTE-585 but did not improve event-free survival. [64]
▸Retrospective evidence should be considered supportive or hypothesis-generating because it is vulnerable to selection bias and does not replace randomized comparisons. [130,133,134]

CP Clinical Pearl: After D2 gastrectomy, the incremental value of postoperative RT remains unresolved; the strongest directly relevant evidence comes from randomized SOX-based trials rather than retrospective series. [19,21]

! Warning: Do not equate improved pathological complete response with proven survival benefit: KEYNOTE-585 improved pCR but did not improve event-free survival. [64]

Scope and current evidence

Concurrent chemoradiation (CRT) has been investigated in gastric and gastroesophageal-junction (GEJ) adenocarcinoma mainly in the neoadjuvant and postoperative settings. The most directly applicable evidence comprises randomized phase III comparisons of preoperative CRT versus chemotherapy, randomized studies of postoperative CRT after D2 gastrectomy, retrospective comparisons of neoadjuvant radiotherapy plus chemotherapy, and a systematic review/meta-analysis of neoadjuvant CRT combined with immune-checkpoint inhibitors (ICIs). ^[16]^A1a^[20]^A1b^[21]^A1b^[19]^A1b^[133]^[134]

Neoadjuvant concurrent chemoradiation

A Chinese, open-label, phase III randomized trial compared perioperative SOX chemotherapy with a regimen incorporating CRT in patients with locally advanced gastric cancer or GEJ adenocarcinoma. ^[20]^A1b The chemotherapy arm received three preoperative cycles of oxaliplatin plus S-1, surgery, and three postoperative SOX cycles. ^[20]^A1b The CRT arm received one SOX cycle, followed by concurrent chemoradiotherapy, a second SOX cycle, surgery, and three postoperative SOX cycles. ^[20]^A1b This design directly evaluates whether inserting preoperative CRT into a perioperative SOX strategy improves outcomes over chemotherapy alone; however, the supplied evidence does not report the trial’s primary endpoint or numerical efficacy and toxicity results. ^[20]^A1b

A 2025 retrospective study compared XELOX plus neoadjuvant radiotherapy with neoadjuvant chemotherapy alone in locally advanced gastric cancer patients undergoing radical gastrectomy and D2 lymph-node dissection. ^[134] The analysis included tumor markers, postoperative pathology, short-term efficacy, postoperative complications, and hospital stay, with inverse-probability methods used to address treatment-selection differences. ^[134] Because this was a single-center retrospective comparison, its findings are supportive but not equivalent to randomized evidence. ^[134]

A retrospective cohort of 256 patients evaluated pathological response and survival after neoadjuvant chemotherapy, neoadjuvant CRT, or neoadjuvant chemoimmunotherapy. ^[130] The cohort included 162 patients treated with chemotherapy, 48 with CRT, and 46 with chemoimmunotherapy. ^[130] Chemoimmunotherapy was associated with improved disease-free survival versus chemotherapy (hazard ratio, 0.75; P = 0.035), but no overall-survival difference was observed; the supplied abstract does not provide a separate numerical comparison of CRT with the other modalities. ^[130]

The 2026 systematic review and meta-analysis summarized clinical trials of neoadjuvant CRT combined with ICIs for locally resectable, locally advanced EGJ or gastric cancer. ^[16]^A1a It was specifically designed to assess efficacy and safety and to provide evidence-based treatment references. ^[16]^A1a This evidence supports active clinical investigation of nCRT plus ICI, but it should not be interpreted as establishing CRT-plus-immunotherapy as a universal standard without the reported pooled estimates, comparative-control details, and mature survival data. ^[16]^A1a

Postoperative CRT after D2 gastrectomy

The role of postoperative RT after an adequate D2 gastrectomy remains unsettled. ^[19]^A1b^[21]^A1b A prospective randomized study enrolled patients with high-risk gastric cancer after D2 resection and compared eight cycles of SOX chemotherapy with postoperative CRT. ^[21]^A1b In the CRT arm, RT was delivered after four to six SOX cycles using intensity-modulated RT to 45 Gy in 25 fractions of 1.8 Gy over five weeks, concurrently with S-1. ^[21]^A1b The study was designed to identify patients who might benefit from adjuvant RT and to assess long-term prognostic outcomes; the supplied abstract does not state the numerical survival results. ^[21]^A1b

A separate open-label, phase III randomized trial evaluated whether adding RT to SOX improves disease-free survival in patients with pathologic T4 or node-positive gastric adenocarcinoma after R0 D2 gastrectomy. ^[19]^A1b It was conducted at five tertiary hospitals in China between 2012 and 2022 and included adults aged 18–70 years. ^[19]^A1b The trial directly addresses the modern postoperative question of CRT versus chemotherapy after D2 surgery, but the supplied evidence does not provide the DFS effect estimate, overall-survival findings, or toxicity results. ^[19]^A1b

Real-world evidence is also available from TJ-ARK01, a retrospective study of 2,489 patients treated at a Chinese cancer center between 2013 and 2017. ^[133] After propensity-score matching, 162 patients receiving chemotherapy and 166 receiving CRT were analyzed to examine the potential benefit of adjuvant CRT, particularly when accurate D2 dissection could not be confirmed. ^[133] These data are hypothesis-generating and may be most relevant where lymphadenectomy or nodal staging is uncertain; they cannot replace randomized evidence. ^[133]

Immunotherapy and non-concurrent radiation evidence

KEYNOTE-585 evaluated perioperative pembrolizumab plus chemotherapy, rather than CRT, in locally advanced gastric or GEJ adenocarcinoma. ^[64]^A1b Pembrolizumab increased pathologic complete response by 10.9 percentage points (95% CI, 7.5%–14.8%; P < 0.00001), but did not improve event-free survival in the parent trial. ^[64]^A1b Thus, pathological response improvement alone does not establish a survival benefit for adding immunotherapy to perioperative treatment. ^[64]^A1b

The CIRCUIT trial investigated nivolumab with palliative hypofractionated RT in 41 patients with unresectable advanced or recurrent gastric cancer after progression on primary and secondary chemotherapy; it was a single-arm phase 1/2 study, not definitive concurrent CRT evidence. ^[132]^C The largest or symptomatic tumors were treated with 22.5 Gy in 5 fractions over five days. ^[132]^C

The remaining supplied studies do not provide direct evidence for gastric CRT: ROBO-CHIP evaluated robotic cytoreduction and HIPEC for limited peritoneal metastases; OGSG 1402 evaluated neoadjuvant docetaxel, cisplatin, and S-1 without RT; a nationwide cohort assessed trastuzumab-based chemotherapy; and the protocol for a network meta-analysis has not yet reported comparative results. ^[127]^[128]^[129]^[135]^D The molecular, laboratory, drug-resistance, and survey studies likewise do not establish CRT efficacy or dosing. [136-141]

Practical interpretation

For resectable locally advanced gastric or GEJ cancer, preoperative CRT and postoperative CRT remain evidence-based investigational or selectively applied strategies whose value depends on disease risk, surgical quality, institutional expertise, and the results of contemporary randomized trials. [16,19-21,133,134] Postoperative RT should be considered particularly cautiously after D2 surgery, because the incremental benefit over modern chemotherapy has not been resolved in the supplied evidence. ^[19]^A1b^[21]^A1b When CRT is used, the clearest reported postoperative regimen is intensity-modulated RT 45 Gy/25 fractions, delivered concurrently with S-1 after systemic SOX chemotherapy. ^[21]^A1b

Evidence directly relevant to gastric or GEJ chemoradiation

Setting	Evidence	Regimen or design	Interpretation
Neoadjuvant	Phase III randomized trial ^[20]^A1b	SOX alone versus SOX, preoperative CRT, surgery, and postoperative SOX	Direct randomized comparison; reported numerical results unavailable in supplied abstract
Postoperative	Prospective randomized study ^[21]^A1b	Eight SOX cycles versus SOX followed by IMRT 45 Gy/25 fractions with concurrent S-1	Evaluates high-risk patients after D2 resection
Postoperative	Phase III randomized trial ^[19]^A1b	Adjuvant SOX versus SOX plus RT after R0 D2 gastrectomy for T4 or node-positive disease	Tests DFS benefit of adding RT
Neoadjuvant	Systematic review/meta-analysis ^[16]^A1a	nCRT plus ICIs for locally resectable locally advanced EGJ/GC	Summarizes efficacy and safety; pooled numerical findings unavailable in supplied abstract
Retrospective	Cohort and real-world studies ^[130]^[133]^[134]	NACRT compared with chemotherapy or other modalities	Supportive but nonrandomized evidence

Adjuvant and Palliative RT

▸The principal recent RT-specific review distinguishes definitive IGC RT (**BED10 >45 Gy**) from high-dose palliative RT (**BED10 >30 Gy**) and challenges the assumption that palliation should always be low-dose and reactive. [17]
▸Evidence for postoperative adjuvant therapy supports benefit in some locally advanced and stage IB populations, but available summaries do not establish an RT-specific effect or a universal postoperative RT strategy. [73,144]
▸Recurrence-pattern analysis after D2 surgery may help select patients and define postoperative RT targets, but the supplied evidence does not report sufficient results for a definitive field recommendation. [81]
▸For advanced disease, RT should be integrated with obstruction management, systemic therapy, nutritional assessment, symptom control, and specialist palliative care. [17,71,76,80,146,147,148]

HY High Yield: The available evidence supports an intent-based RT strategy: postoperative RT is selective, definitive RT is reserved for appropriately fit patients with non-metastatic inoperable disease, and palliative RT should be matched to symptom urgency and expected benefit. [17,73,81]

! Warning: Do not infer an RT-specific survival benefit from studies of adjuvant therapy in general, and do not adopt a definitive dose or target volume solely from the supplied abstracts because key comparative outcomes and detailed recurrence-pattern results are not reported. [73,81,144]

Scope and evidence base

Radiotherapy (RT) has two distinct roles in gastric cancer: postoperative adjuvant treatment after potentially curative surgery and symptom-directed or local-control treatment for unresectable or metastatic disease. The contemporary evidence base is heterogeneous, comprising systematic reviews, retrospective cohorts, and observational studies rather than a uniform set of randomized RT trials. The most directly relevant recent review specifically reassessed definitive and high-dose palliative RT for inoperable gastric cancer (IGC), because practice commonly uses low-dose, reactive RT for symptoms such as bleeding, whereas higher-dose treatment has stronger supporting evidence in oesophageal cancer. ^[17]^A1a

Adjuvant RT after gastrectomy

Adjuvant therapy after surgery is associated with improved outcomes in locally advanced gastric cancer in aggregate, but regimens and treatment strategies are not uniform. A systematic review and meta-analysis evaluated randomized clinical trials comparing surgery plus adjuvant therapy with surgery alone, with overall survival (OS), relapse-free survival, and disease-free survival as outcomes; the supplied evidence summary does not provide pooled effect estimates or establish the independent contribution of RT. ^[73]^A1a Consequently, adjuvant RT should not be presented as universally equivalent to perioperative or postoperative systemic therapy, and treatment selection should account for disease stage, resection quality, nodal evaluation, and the systemic-therapy plan. ^[73]^A1a

Evidence for stage IB disease remains uncertain. In a retrospective cohort of 510 patients after gastrectomy, postoperative adjuvant therapy was associated with a higher 5-year OS than surgery alone (92.9% vs 86.7%), while 5-year disease-free survival did not differ significantly; the report assessed adjuvant therapy generally and does not establish a specific benefit for RT. ^[144]

After D2 lymphadenectomy, recurrence-pattern data may help refine selection and target volumes. A retrospective study analyzed 1,169 patients with stage I–III gastric cancer, including 225 patients who developed recurrence, and examined regional recurrence, vertical distribution of recurrence at lymph-node station 16, and risk factors for locoregional failure to inform postoperative RT. ^[81]^B3b Because the supplied abstract does not report the recurrence distribution, predictive factors, or a validated target-volume recommendation, these findings should be regarded as hypothesis-generating rather than a basis for a specific field design. ^[81]^B3b

Long-term toxicity should be included in adjuvant decision-making. A SEER-based retrospective cohort included 24,777 surgically treated, non-metastatic gastric cancer patients diagnosed from 2000–2018, of whom 6,128 received adjuvant RT, and evaluated second primary malignancies after an appropriate latency period. ^[142] The supplied evidence does not report the association estimate or identify determinants; therefore, it confirms the importance of surveillance for late effects but does not quantify second-primary-malignancy risk attributable to RT. ^[142]

Definitive and high-dose palliative RT for inoperable disease

The systematic review by Case and colleagues defined definitive RT as treatment for non-metastatic IGC with a BED10 >45 Gy and high-dose palliative RT as treatment for symptoms or local control with a minimum BED10 >30 Gy. ^[17]^A1a The review was prospectively registered, followed PRISMA standards, searched MEDLINE, EMBASE, and the Cochrane Library, and also reviewed meeting proceedings and clinical-trial registries. ^[17]^A1a Its clinical premise is that selected patients with inoperable, non-metastatic disease or a dominant symptomatic/local problem may warrant evaluation of doses above conventional reactive palliation; however, the supplied abstract does not provide the included-study results, comparative outcomes, toxicity rates, or a definitive practice recommendation. ^[17]^A1a

RT should therefore be individualized according to intent: definitive treatment requires adequate performance status, expected survival, and the ability to tolerate a potentially more intensive course, whereas palliative treatment should prioritize rapid symptom relief, treatment burden, and the likelihood of local re-progression. These principles are consistent with the broader palliative-care literature, which emphasizes symptom burden and patient-centered goals in advanced gastric cancer. ^[76]^B2a Psychosocial functioning is also clinically relevant because advanced oesophagogastric cancer is associated with impaired psychosocial well-being; a mixed-methods systematic review identified this burden and the need for assessment and intervention. ^[70]^B2a

Integration with other palliative interventions

RT is one component of multimodality palliation and should not delay interventions required for mechanical complications. For malignant gastric outlet obstruction, a meta-analysis of 31 studies involving 2,444 patients found similar clinical success between gastrojejunostomy and endoscopic stenting, while gastrojejunostomy had lower re-obstruction and reintervention and longer hospitalization; in the gastric-cancer subgroup, gastrojejunostomy was associated with better survival. ^[71]^B2a Observational surgical series likewise evaluated symptom improvement, oral intake, discharge home, hospitalization-free “good days,” and receipt of systemic treatment after palliative surgery. ^[147] In unresectable gastric cancer with outlet obstruction, stomach-partitioning gastrojejunostomy reduced delayed gastric emptying, vomiting, and prokinetic use compared with conventional gastrojejunostomy in a propensity-matched cohort. ^[148]

Other non-RT approaches include palliative gastrectomy, although a systematic review and meta-analysis found that its survival benefit in advanced gastric cancer remains debated and analyzed observational associations rather than definitive randomized evidence. ^[75]^B2a For peritoneal metastases, a 2024 systematic review and meta-analysis evaluated repeated normothermic catheter-based intraperitoneal chemotherapy and pressurized intraperitoneal aerosol chemotherapy, which deliver higher intraperitoneal drug concentrations than intravenous administration; overall survival was the primary outcome, but the supplied summary does not report pooled results. ^[72]^A1a

Systemic treatment eligibility and supportive care are essential when considering RT. Sarcopenia was present in approximately 48.05% of patients in a meta-analysis of 668 advanced gastric cancer patients receiving palliative chemotherapy and was evaluated as a prognostic marker for OS and progression-free survival. ^[77]^B2a Older adults may require individualized assessment because patients aged 75 years or more have historically been underrepresented in trials; a retrospective study examined palliative chemotherapy patterns and survival in 307 older patients with advanced oesophageal or gastric carcinoma. ^[146] Specialist palliative-care involvement is relevant to utilization and goals of care: a Finnish nationwide study found that only 32% of 732 patients who died from oesophageal or gastric cancer had specialist palliative-care contact, including 21% with contact more than 30 days before death. ^[80]^B3b A U.S. National Inpatient Sample study similarly examined sociodemographic disparities and outcomes associated with palliative-care use during end-of-life hospitalizations for gastric cancer. ^[78]^B3b

Practical synthesis

Use adjuvant RT selectively rather than routinely when the expected locoregional benefit outweighs toxicity and competing systemic relapse risk. ^[73]^A1a^[81]^B3b^[142] For inoperable disease, consider definitive or high-dose palliative RT when the patient has a meaningful expected survival, a localized treatment objective, and sufficient fitness for the proposed BED10 threshold; use shorter, lower-burden palliation when immediate symptom control is the priority. ^[17]^A1a Bleeding, pain, obstruction, and progressive local disease should be managed within multidisciplinary care, with endoscopic, surgical, systemic, nutritional, and specialist palliative options considered alongside RT. ^[17]^A1a^[71]^B2a^[76]^B2a^[80]^B3b^[147]^[148]

RT intent and evidence-informed selection

Clinical setting	Evidence-informed RT concept	Important limitations
Postoperative, potentially curative disease	Consider selectively in the context of stage, nodal risk, resection quality, recurrence pattern, and systemic therapy. ^[73]^A1a^[81]^B3b	Meta-analytic evidence concerns adjuvant therapy broadly; an RT-specific pooled benefit is not provided. ^[73]^A1a
Inoperable, non-metastatic disease	Definitive RT was defined as BED10 >45 Gy in the 2024 systematic review. ^[17]^A1a	Supplied data do not report comparative efficacy, toxicity, or definitive recommendations. ^[17]^A1a
Symptomatic or locally progressive inoperable disease	High-dose palliative RT was defined as minimum BED10 >30 Gy for symptom or local control. ^[17]^A1a	Treatment should be balanced against performance status, prognosis, competing metastatic disease, and treatment burden. ^[17]^A1a^[76]^B2a
Mechanical gastric outlet obstruction	Evaluate stenting, gastrojejunostomy, or other procedural treatment when rapid restoration of intake is required. ^[71]^B2a^[147]^[148]	RT may not provide sufficiently rapid relief of fixed obstruction and should not replace urgent mechanical palliation. ^[71]^B2a^[148]

Acute and Late Toxicity

▸The supplied references provide evidence on postgastrectomy surgical morbidity and functional sequelae, not direct gastric-radiotherapy toxicity. [85–102,149–151]
▸Duodenal-stump fistula or leakage has reported incidence **1.6–5%**, morbidity up to **75%**, and mortality of **16–20%** in the cited background evidence. [91]
▸Important acute complications include anastomotic leak, intra-abdominal infection, pancreatic fistula, pulmonary complications, abscess, and surgical-site infection. [90–92,100,150]
▸Pylorus-preserving gastrectomy increases delayed gastric emptying and gastric stasis but may reduce dumping syndrome and improve nutritional status. [90]
▸Reconstruction affects reflux and dysphagia; double-flap and double-tract techniques were specifically evaluated after proximal gastrectomy, while jejunal orientation was evaluated after total gastrectomy. [85,87,101]
▸Risk-stratified and time-sequential surveillance may improve detection of postoperative complications, particularly in patients with asthma, advanced age, or substantial comorbidity. [89,96,99,100]

! Warning: Do not use these surgical outcome studies to estimate acute or late toxicity from gastric radiotherapy; dedicated radiation oncology evidence is required. [85–102,149–151]

CP Clinical Pearl: For postoperative safety reporting, specify complication definitions, timing, severity grade, reconstruction type, and relevant patient risk factors; standardized classification and sequential prediction were specifically addressed in the supplied evidence. [99,149]

Scope and interpretation

The supplied evidence addresses toxicity predominantly as postoperative morbidity after gastrectomy and reconstruction rather than as radiation-specific toxicity. No included reference directly evaluates acute or late adverse effects of gastric radiotherapy, radiochemotherapy, dose–volume relationships, radiation gastritis, ulceration, bleeding, perforation, strictures, renal toxicity, or radiation-induced secondary malignancy; therefore, these outcomes should not be extrapolated from the surgical literature. [85–102,149–151]

Acute postoperative morbidity

Postgastrectomy complications include anastomotic leakage or bleeding, anastomotic stricture, duodenal-stump leakage, intra-abdominal infection or abscess, pancreatic fistula, pulmonary infection, surgical-site infection, delayed gastric emptying, gastric stasis, and other clinically significant events. [90–92,150] A Korean expert task force involving 14 high-volume hospitals developed a standardized complication classification for gastrectomy through 10 formal meetings incorporating literature, international guidelines, and randomized-trial evidence; this framework is relevant when reporting acute toxicity consistently across institutions. ^[149]

Duodenal-stump fistula or leakage is reported as an uncommon but severe complication after distal or total gastrectomy, with an incidence of 1.6–5%, morbidity of up to 75%, and mortality of 16–20% in the cited meta-analysis background. ^[91]^B2a The meta-analysis specifically compared reinforcement versus no reinforcement of the duodenal stump, but the supplied abstract does not provide the pooled effect estimate; reinforcement should therefore be considered a risk-reduction strategy under evaluation rather than a universally established standard. ^[91]^B2a

In minimally invasive gastrectomy, serious intra-abdominal infectious complications include anastomotic leakage, pancreatic fistula, and intra-abdominal abscess. ^[150] A prospective, multicenter, single-arm clinical trial evaluated polyglycolic-acid sheets for prevention of Clavien–Dindo grade ≥III intra-abdominal infectious complications after minimally invasive distal or total gastrectomy, but the supplied abstract does not report the final event rate or comparative efficacy. ^[150] Pancreatic complications remain an important acute toxicity domain, particularly during suprapancreatic lymph-node dissection. ^[94]^C4^[95]^B3b Retrospective evidence examined the association between preoperative left gastric-vein anatomy on contrast-enhanced CT and clinically relevant postoperative pancreatic fistula after minimally invasive gastrectomy. ^[94]^C4 A separate retrospective cohort evaluated a pancreas-contactless technique during open gastrectomy, in which the pancreas was avoided during suprapancreatic exposure, compared with conventional pancreatic contact. ^[95]^B3b

Asthma was identified as a risk factor for postoperative pulmonary complications and intra-abdominal infectious complications in a retrospective cohort of 1,001 gastrectomy patients. ^[100]^B3b Machine-learning models using perioperative information were developed to predict complications sequentially from postoperative day 1, postoperative day 3, and more recent biochemical and vital-sign data, supporting dynamic rather than exclusively preoperative surveillance. ^[99]^B3b In elderly patients, a systematic review evaluated limited versus D2 lymphadenectomy for postoperative complications, pancreatic fistula, abdominal abscess, hospital stay, and overall survival; the available abstract confirms seven retrospective studies but does not provide pooled numerical results. ^[89]^B2a

Reconstruction-related functional toxicity

Reconstruction substantially influences reflux, dysphagia, gastric emptying, and nutritional outcomes. After proximal gastrectomy, gastroesophageal reflux is a recognized complication; a 2026 systematic review compared the double-flap technique with other reconstructions using subjective symptoms, endoscopy, and proton-pump-inhibitor use as reflux outcomes. ^[85]^A1a In a meta-analysis of randomized and propensity-score-matched studies, proximal gastrectomy with double-tract reconstruction was compared with total gastrectomy for short- and long-term postoperative outcomes in early and advanced gastric cancer, but the supplied abstract does not provide the pooled estimates. ^[87]^A1a

Laparoscopic pylorus-preserving gastrectomy was associated with more delayed gastric emptying and gastric stasis than laparoscopic distal gastrectomy, while pulmonary complications, anastomotic leakage, pancreatic fistula, and other complications did not significantly differ in the cited meta-analysis. ^[90]^B2a Pylorus preservation appeared more favorable for preventing dumping syndrome and improving nutritional status, although the abstract concludes that its overall additional benefit was limited. ^[90]^B2a After total gastrectomy with esophagojejunostomy, dysphagia was investigated in relation to jejunal orientation; the retrospective cohort included 116 patients, but the supplied abstract does not state the comparative incidence or adjusted effect. ^[101]^C4

Procedure-related modifiers and late considerations

Robotic-assisted total gastrectomy was systematically compared with laparoscopic-assisted total gastrectomy in studies published before October 2023, with outcomes including operative and postoperative safety; the supplied abstract does not provide the pooled complication estimates. ^[86]^A1a Other comparative evidence assessed robotic versus laparoscopic gastrectomy by comorbidity burden, including short-term outcomes and overall and recurrence-free survival, in 1,501 patients stratified by the modified age-adjusted Charlson Comorbidity Index. ^[96]^B3b A separate propensity-matched retrospective study of 1,538 patients with stage I–III disease compared perioperative outcomes and three-year survival between robotic and laparoscopic gastrectomy; robotic surgery showed slightly shorter operative time and lower blood loss in the supplied results. ^[102]^B3b

Intracorporeal versus extracorporeal esophagojejunostomy after laparoscopic total gastrectomy was evaluated for leak, bleeding, stricture, infection, duodenal-stump leak, pancreatic fistula, and other perioperative outcomes, but the supplied abstract does not state pooled estimates. ^[92]^B2a Spleen-preserving total gastrectomy was compared with splenectomy for proximal gastric cancer in a systematic review of randomized and observational studies focused on intraoperative and postoperative complications. ^[93]^A1a For remnant gastric cancer, subtotal gastrectomy was compared with completion total gastrectomy because completion surgery is technically demanding and associated with substantial morbidity; the supplied abstract does not provide comparative pooled outcomes or establish oncologic equivalence. ^[88]^C4

Patients who have undergone altered gastric anatomy may also experience later treatment complexity: common bile duct stones can be difficult to manage with conventional ERCP, and a cohort evaluated single-stage laparoscopic cholecystectomy with common bile duct exploration after previous gastric surgery. ^[151]^C These findings concern post-surgical anatomy rather than radiation toxicity and should be used only when planning long-term survivorship care. ^[151]^C

Evidence-informed toxicity domains after gastric cancer surgery

Toxicity domain	Evidence-supported considerations
Anastomotic and stump complications	Leak, bleeding, stricture, and duodenal-stump fistula are evaluated across reconstruction and reinforcement strategies; duodenal-stump fistula has reported incidence 1.6–5%. ^[91]^B2a^[92]^B2a
Infectious complications	Intra-abdominal abscess, intra-abdominal infection, pulmonary infection, and surgical-site infection are important acute outcomes. [90–92,100,150]
Pancreatic complications	Pancreatic fistula is associated with suprapancreatic dissection and has been studied in relation to left gastric-vein anatomy and pancreas-contactless technique. ^[94]^C4^[95]^B3b
Functional complications	Reflux, dysphagia, delayed gastric emptying, gastric stasis, dumping syndrome, and nutritional impairment vary with reconstruction. ^[85]^A1a^[87]^A1a^[90]^B2a^[101]^C4
High-risk populations	Age, comorbidity burden, and asthma may modify postoperative risk and surveillance needs. ^[89]^B2a^[96]^B3b^[99]^B3b^[100]^B3b
Radiation-specific toxicity	Not directly evaluated by the supplied references; surgical data should not be substituted for radiotherapy toxicity evidence. [85–102,149–151]

Outcomes

▸A phase 3 randomized trial is evaluating postoperative RT plus SOX versus SOX alone after R0 D2 gastrectomy in patients with pathologic T4 or node-positive gastric cancer, with DFS as the principal endpoint; the supplied abstract does not report the comparative DFS or OS results. [19]
▸For tsMHC-II-positive operable cT3-4aN+M0 disease, perioperative tislelizumab plus chemotherapy increased major pathological response from 26.5% to 61.8% versus chemotherapy alone. [154]
▸The supplied nCRT+ICI meta-analysis evaluates efficacy and safety in locally advanced EGJ or gastric cancer, but its abstract is truncated before pooled numerical outcomes. [16]
▸Systemic ICI-based strategies improve survival versus chemotherapy in network-meta-analysis evidence, but these findings do not directly establish a benefit from gastric RT. [160]
▸Radiomics, thyroid-function measures, immune-cell profiles, HER2 status, and CRP kinetics are investigational prognostic or predictive factors and are not validated indications for gastric RT selection. [158,162,163,165,167,168]

! Warning: Do not extrapolate perioperative immunotherapy, HER2-directed therapy, radiomics, or retrospective biomarker findings into a definitive indication for gastric RT. The supplied references do not provide mature, direct evidence for definitive or palliative RT outcomes. [16,157,158,160,162,163,165,167,168]

CP Clinical Pearl: When postoperative RT is considered after D2 gastrectomy, outcome interpretation should distinguish the modern D2-surgery context from historical studies involving less extensive lymphadenectomy. The supplied phase 3 trial was specifically designed to address this contemporary setting. [19]

Overview

Contemporary outcome evidence for gastric-cancer radiation management is increasingly integrated with perioperative chemotherapy and immune checkpoint inhibition. The most directly relevant randomized evidence evaluates whether postoperative radiotherapy (RT) adds benefit after an oncologically adequate D2 gastrectomy, while newer studies assess neoadjuvant chemoradiotherapy (nCRT) combined with immunotherapy. Evidence for definitive or palliative RT-specific endpoints remains limited in the supplied references.

Postoperative chemoradiotherapy after D2 gastrectomy

A phase 3, open-label randomized clinical trial conducted at five tertiary hospitals in China evaluated adjuvant SOX chemotherapy with or without postoperative RT in patients with gastric adenocarcinoma who had undergone R0 resection and D2 lymphadenectomy. Eligible patients had pathologic T4 or node-positive disease, and the primary objective was to determine whether adding RT improved disease-free survival (DFS). ^[19]^A1b The supplied abstract identifies DFS as the principal endpoint but does not provide the comparative DFS result, overall-survival result, recurrence pattern, or toxicity estimates; these outcomes should therefore not be inferred from the available evidence. ^[19]^A1b

This trial is clinically important because it addresses the modern question of whether RT remains beneficial after D2 surgery rather than after limited lymphadenectomy. ^[19]^A1b Until the complete numerical results and subgroup analyses are available, the evidence supports viewing postoperative RT after D2 gastrectomy as an actively evaluated strategy, not as a universally established addition to SOX for every T4 or node-positive patient. ^[19]^A1b

Neoadjuvant chemoradiotherapy plus immunotherapy

A systematic review and meta-analysis summarized clinical trials of nCRT combined with immune checkpoint inhibitors (nCRT+ICIs) for locally resectable, locally advanced esophagogastric-junction or gastric cancer. ^[16]^A1a The study was designed to evaluate efficacy and safety and to provide pooled clinical evidence for this emerging treatment approach. ^[16]^A1a However, the supplied abstract is truncated before the numerical efficacy and safety results; pooled pathological response, R0-resection, survival, postoperative morbidity, and immune-related adverse-event estimates cannot be reported reliably from the provided text. ^[16]^A1a

The outcome framework for nCRT+ICIs should therefore include pathological response, R0 resection, DFS, overall survival, postoperative complications, treatment completion, and immune-related toxicity, but the available reference does not establish threshold values for these endpoints. ^[16]^A1a

Perioperative immunotherapy outcomes relevant to multimodality care

In the randomized phase 2 Mountain-02 trial, 136 patients with operable cT3-4aN+M0 gastric or gastroesophageal-junction cancer received perioperative tislelizumab plus chemotherapy or chemotherapy alone. Among patients whose tumors were positive for tumor-specific MHC class II, major pathological response (mPR) was significantly higher with tislelizumab plus chemotherapy than with chemotherapy alone (61.8% vs 26.5%; P=0.003). ^[154] No significant benefit was observed in the tsMHC-II-negative subgroup according to the supplied abstract, indicating that pathological response may vary according to biomarker-defined subgroups. ^[154]

In the Asian subgroup of the RATIONALE-305 first-line advanced or metastatic gastric/GEJ adenocarcinoma trial, 748 patients were analyzed for patient-reported outcomes: 376 received tislelizumab plus chemotherapy and 372 received placebo plus chemotherapy. ^[155] At cycle 4, both treatment groups showed clinically meaningful improvement in patient-reported measures; the supplied abstract does not provide the complete between-group estimates or time-to-deterioration results. ^[155] These findings are relevant when judging treatment burden and quality of life, although they do not directly establish a benefit from gastric RT. ^[155]

Network meta-analysis of 11 randomized trials involving 8,999 patients found that both dual-target ICI–chemotherapy and single-ICI–chemotherapy strategies significantly improved survival compared with chemotherapy, although the supplied abstract does not report regimen-specific hazard ratios or absolute OS and PFS values. ^[160] A separate meta-analysis of six studies involving 1,097 patients evaluated ICIs combined with trastuzumab and chemotherapy for advanced HER2-positive gastric/GEJ cancer; it analyzed OS, PFS, objective response, disease control, and safety, but the supplied abstract does not provide the pooled estimates. ^[157]

Other outcome predictors and treatment-related evidence

Cadonilimab efficacy and safety were evaluated in a meta-analysis of 13 studies involving 1,359 patients with solid tumors, including randomized and single-arm studies; assessed outcomes included objective response, disease control, OS, PFS, and adverse events. ^[152] The supplied abstract does not provide gastric-cancer-specific estimates, so these data should not be used as direct evidence for RT outcomes. ^[152]

Retrospective studies suggest potential biomarkers for response to neoadjuvant systemic therapy, including pretreatment CT-radiomics, treatment-specific radiomics, baseline thyroid function, treatment-emergent thyroid dysfunction, and post-treatment immune-cell profiles. ^[158]^[163]^[165]^[168] These studies are nonrandomized or retrospective and report predictive or prognostic associations rather than validated criteria for selecting gastric RT. ^[158]^[163]^[165]^[168] HER2 overexpression was present in approximately 16% of gastric-cancer patients in a 39-study meta-analysis of 19,903 patients and was associated with worse OS (pooled HR 1.30); this is prognostic evidence, not evidence that RT improves outcomes in HER2-positive disease. ^[162]

Evidence not directly establishing gastric RT outcomes

The remaining supplied studies primarily address surgery, prevention, or non-gastric malignancy and do not establish gastric RT efficacy. Robot-assisted distal gastrectomy research evaluated trocar-port models and perioperative surgical outcomes. ^[153] Endoscopic submucosal dissection versus surgery in patients aged ≥75 years with early gastric cancer meeting curative criteria showed 5-year OS of 84.8% versus 82.9%, respectively, without a significant OS difference; these results apply to local endoscopic or surgical management rather than RT. ^[169]^C Studies of adolescent Helicobacter pylori screening and eradication, antibiotic regimens, and lactoferrin address prevention or infection treatment rather than cancer radiation outcomes. ^[159]^[161] Early-onset gastric cancer, ERBB2-low versus ERBB2-null metastatic disease, CRP kinetics during PD-1 therapy, and the prostate-cancer ENABLE sub-analysis likewise do not provide direct evidence for gastric RT. ^[164]^[166]^[167]^[156]

Practical interpretation

The supplied evidence supports reporting outcomes separately by treatment setting: postoperative RT after D2 surgery should be judged primarily by DFS, OS, recurrence distribution, and toxicity; nCRT+ICI by pathological response, resection quality, survival, and perioperative safety; and systemic immunotherapy by survival, response, patient-reported outcomes, and immune-related adverse events. ^[16]^A1a^[19]^A1b^[154]^[155]^[157]^[160] Numerical conclusions about RT benefit should remain provisional until complete trial-level results are available. ^[16]^A1a^[19]^A1b

Outcome evidence relevant to gastric cancer radiation management

Setting	Population/intervention	Reported outcome evidence	Limitations
Postoperative RT	T4 or node-positive gastric adenocarcinoma after R0 D2 gastrectomy; SOX with or without RT	DFS was the primary endpoint of a phase 3 randomized trial	Comparative DFS, OS, recurrence, and toxicity values are not provided in the supplied abstract. ^[19]^A1b
Neoadjuvant nCRT+ICI	Locally advanced, locally resectable EGJ or gastric cancer	Systematic review/meta-analysis assessed efficacy and safety	Numerical pooled response, survival, resection, and toxicity outcomes are unavailable in the supplied abstract. ^[16]^A1a
Perioperative immunotherapy	cT3-4aN+M0 gastric/GEJ cancer; tislelizumab plus chemotherapy	In tsMHC-II-positive tumors, mPR was 61.8% versus 26.5% with chemotherapy alone	Biomarker-stratified phase 2 evidence; not a direct RT comparison. ^[154]
Advanced disease	First-line ICI–chemotherapy strategies	Network meta-analysis found survival benefit versus chemotherapy	Regimen-specific OS/PFS estimates are not provided; evidence is not RT-specific. ^[160]

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Gastric Cancer Radiation Management

Quick Reference

Overview and Recommendations

Background

Evaluation

Management

Board Review — High Yield

Deep Dive — Evidence Details

Indications by Stage

External Beam Radiotherapy (EBRT)

Clinical role and treatment intent

Definitive EBRT for inoperable or unresectable disease

Postoperative chemoradiotherapy

Planning technique and organ protection

Toxicity, nutrition, and supportive care

Practical synthesis

Brachytherapy

Scope and rationale

Image-guided interstitial brachytherapy for metastases

CT-guided permanent seed implantation for locoregional recurrence

Preclinical evidence and biological effects

Evidence boundaries and related techniques

Practical interpretation

Concurrent Chemoradiation

Scope and current evidence

Neoadjuvant concurrent chemoradiation

Postoperative CRT after D2 gastrectomy

Immunotherapy and non-concurrent radiation evidence

Practical interpretation

Adjuvant and Palliative RT

Scope and evidence base

Adjuvant RT after gastrectomy

Definitive and high-dose palliative RT for inoperable disease

Integration with other palliative interventions

Practical synthesis

Acute and Late Toxicity

Scope and interpretation

Acute postoperative morbidity

Reconstruction-related functional toxicity

Procedure-related modifiers and late considerations

Outcomes

Overview

Postoperative chemoradiotherapy after D2 gastrectomy

Neoadjuvant chemoradiotherapy plus immunotherapy

Perioperative immunotherapy outcomes relevant to multimodality care

Other outcome predictors and treatment-related evidence

Evidence not directly establishing gastric RT outcomes

Practical interpretation

Related Pages

References

Backlinks