Lymphomas — Board Review Summary
CROSS-CUTTING CONCEPTS (Both HL and NHL)
Staging, Workup, and Response Assessment
- Lugano 2014 (modifies Ann Arbor): Limited = non-bulky I–II; Advanced = III–IV. Bulky I–II may be limited or advanced by histology/prognostic factors. "E" only in limited stage (IE = extranodal without nodes; IIE = direct extension to non-nodal). "X" designation eliminated — record max tumor diameter instead (by PET-CT for FDG-avid disease).
- Workup: incisional/excisional bx (never FNA alone), CBC with diff, LDH (NHL), ESR + albumin (HL), PET-CT (all FDG-avid). Bone marrow bx: not needed for HL if PET-CT done; still needed for FL; not needed for DLBCL if PET shows bone/BM involvement.
- B symptoms: unexplained fever >38°C (>101°F), drenching night sweats, weight loss >10% body mass over 6 months. HL-specific: pruritus, fatigue, alcohol-induced pain.
Deauville 5-point scale (memorize cold): (1) no uptake · (2) uptake ≤ mediastinal blood pool · (3) uptake ≤ liver · (4) moderately > liver · (5) markedly > liver or new lesions. De-escalation cutoff is usually 1–2 (blood pool); standard PET-negative is 1–3 (liver). Boards love the distinction.
ISRT / ISRT Nomenclature
- ISRT (Wirth IJROBP 2020) is current standard. Post-chemo consolidation: CTV may be strictly limited to sites evident at diagnosis. RT alone: CTV includes all evident sites plus adjacent volume potentially harboring subclinical disease. Extranodal: typically entire involved organ (exceptions: bone, soft tissue, skin, lungs, liver, selected eye).
- Newer NCTN nomenclature (Saifi Lancet Haematol 2024): ISRT, RSRT (response-adapted), pISRT, pRSRT, pRPRT — distinguishing pre-chemo CT vs PET vs post-chemo PET.
PART I — HODGKIN LYMPHOMA
Pathology (WHO/ICC 2022)
- Classical HL (95%): CD15+, CD30+, CD20–. Subtypes: nodular sclerosing (~75%, mediastinal/women/young adults), mixed cellularity (20–25%, older, more advanced stage), lymphocyte-rich (5%), lymphocyte-depleted (rare, HIV association).
- NLPHL (5%): CD15–, CD30–, CD20+. ICC 2022 renamed as "nodular lymphocyte predominant B-cell lymphoma" — a classification change that can show up on boards.
Prognostic Factors (Limited Stage HL)
| Factor | GHSG (unfavorable if any) | EORTC (unfavorable if any) |
|---|---|---|
| Age | — | ≥50 |
| ESR / B symptoms | ESR ≥50, or ≥30 with B sx | ESR ≥50, or ≥30 with B sx |
| Large mediastinal adenopathy | Yes (MMR >1/3) | Yes (MTR >0.35) |
| Extranodal sites | Any E site | — |
| Number of nodal sites | ≥3 | ≥4 |
Early-Stage cHL Management
| Risk / Trial | Arm | Outcome |
|---|---|---|
| Favorable (GHSG HD10) | ABVD × 2 → ISRT 20 Gy | 10y PFS 87% |
| Unfavorable (GHSG HD11) | ABVD × 4 → ISRT 30 Gy | 10y PFS 84% (20 Gy inferior) |
| PET-adapted fav (HD16) | ABVD × 2 → PET-neg: no RT vs + RT | 5y PFS 86.7% vs 94.2% (Δ 7.5%) |
| PET-adapted unfav (HD17) | eBEACOPP × 2 + ABVD × 2 → ± IFRT | 5y PFS 95.1% vs 97.3% |
| RAPID | ABVD × 3 → PET-neg: no RT vs + RT | Δ PFS 3.7–6% |
| H10F (favorable) | ABVD × 4 chemo-alone vs ABVD × 3 + RT | Δ PFS 12% |
Bottom line from PET-adapted trials: omitting RT after CR costs 3–12% 5y PFS (though usually not OS). The canonical board answer remains ABVD × 2 + 20 Gy (favorable) or ABVD × 4 + 30 Gy (unfavorable). PET adaptation is acceptable for specific scenarios but boards tend to test standard arms.
Evolving early cHL systemic regimens (recognize the names): BV-AVD (brentuximab vedotin + AVD — BREACH, MSKCC pilot), N-AVD / nivo-AVD (NIVAHL), BV-Nivo → AD (Abramson Blood 2025). AHOD2131 and RADAR are ongoing Phase III. Trend: substituting novel agents for bleomycin to preserve efficacy while reducing pulmonary/cardiac toxicity.
Advanced cHL Management
| Trial | Regimen | PFS |
|---|---|---|
| ECHELON-1 (Ansell NEJM 2022) | BV-AVD vs ABVD | 6y PFS 82.3% vs 74.5%; 6y OS 93.9% vs 89.4% |
| SWOG 1826 (Herrera NEJM 2024) | N-AVD vs BV-AVD | 2y PFS 92% vs 83% — nivo-AVD new standard |
| GHSG HD15 | eBEACOPP × 6–8; no RT if residual <2.5 cm or PET-neg | 4y PFS 92.1% |
| GHSG HD18 | PET2-adapted eBEACOPP ± R × 4–6 | 3y PFS 93.5% |
| RATHL | ABVD × 6 (drop bleo if PET2-CR) | 3y PFS 85% |
| HD0607 / HD0801 | ABVD × 6, if PET-CR: bulky >5 cm randomized to ± RT | No difference — RT omission safe in this subset |
Current standard advanced cHL: 6 cycles nivo-AVD; no role for RT if PET-CR. Boards still test older ABVD data, but SWOG 1826 is now the frontline reference.
R/R cHL
- Standard: second-line therapy (e.g., BV-Nivo, ICE, salvage regimens) → ASCT (Linch Lancet 1993; Schmitz Lancet 2002 established transplant benefit).
- RT role in R/R: localized disease encompassable by a reasonable field; bulky sites ≥5 cm; locoregional disease with incomplete response to reinduction; sites where LC is critical (cord, SVC, nerve root, airway, GU/GI obstruction).
- Transplant-free salvage for low-risk relapse: Checkmate-744 (BV/Nivo → ISRT 30.6 Gy; 3y EFS 87%), EuroNET-PHL-R1, AHOD0431.
NLPHL (now "nodular lymphocyte predominant B-cell lymphoma" per ICC)
- Male predominance, peripheral nodal presentation, late relapses — re-biopsy at relapse to r/o transformation to DLBCL.
- Stage I or stage II with contiguous nodal involvement: ISRT 24–30 Gy alone (Global NLPHL One Working Group data; observation has ~25% relapse at 10y; RT-containing arms have PFS ~95%).
Mediastinal HL RT technique (testable): DIBH (deep inspiratory breath hold) — reduces mean heart, LV, LAD dose. In women: arms down with incline (reduces breast dose). Target NCCN constraints: heart mean <8 Gy, LV mean <8 Gy, LAD V15 <10%, lungs mean <13.5 Gy / V20 <20%, thyroid V25 <62.5%, breasts mean <4 Gy.
Maraldo Lancet Haematol 2015 cardiac risk data: HR for CVD rises with both cumulative anthracycline dose and mean heart RT dose. Key decision point — 2 extra cycles of ABVD vs adding 20 Gy ISRT: 20 Gy with DIBH often gives lower CVD HR than additional anthracycline. This rationale underpins the current preference for abbreviated chemo + low-dose RT over extended chemo alone.
PART II — NON-HODGKIN LYMPHOMA: AGGRESSIVE
DLBCL
IPI (memorize)
| Factor | IPI | aa-IPI (age ≤60) |
|---|---|---|
| Age >60 | 1 | — |
| LDH > ULN | 1 | 1 |
| PS 2–4 | 1 | 1 |
| >1 extranodal site | 1 | — |
| Stage III–IV | 1 | 1 |
Dose Escalation / De-escalation
Lowry Rad Onc 2011 (Phase III): 30 Gy/15 fx vs 40–45 Gy/20–23 fx in aggressive NHL (82% DLBCL, 73% after chemo). No difference in LC, PFS, or OS. Established 30 Gy as standard for CR after chemo. No PET assessment in this trial — pre-PET era.
ILROG Phase II 20 Gy trial (Kelsey ASTRO 2025): 243 DLBCL pts (66% stage I–II, 32% bulky) with Deauville 1–3 after ≥3 cycles of R-chemo got 20 Gy. 3y FFLR 98.6%. Supports 20 Gy as emerging standard for PET-CR after full-dose chemo.
Indications for Consolidation RT (DLBCL)
- Bulky disease ≥7.5 cm (Held JCO 2014; Thurner HemaSphere 2023)
- Skeletal site involvement (Held JCO 2013)
- Critical LC sites: cord/nerve root compression, bleeding, obstruction
- Limited stage treated with abbreviated chemo (<4 cycles full-dose R-chemo) — RT compensates for reduced chemo and carries lower heme/neuro/cardiac toxicity than extended chemo (Odejide 2015; Pinnix 2017; Abuamsha Hematol Onc 2019 showed reduced CV mortality).
- Incomplete response to chemo (PET-positive after induction)
PET-Response-Adapted DLBCL Trials
| Trial | Population | Key finding |
|---|---|---|
| LYSA (Lamy Blood 2018) | Limited, nonbulky (<7 cm) | PET-CR after R-CHOP-14 × 4: 5y EFS 92% (RT) vs 89% (no RT) — non-inferior |
| SWOG 1001 (Persky JCO 2020) | Limited, nonbulky (<10 cm) | R-CHOP × 3 + PET: if CR, 1 more cycle, no RT → 5y PFS 89%. If PET+ → 36 Gy IFRT + 9 Gy boost + Y-90 → 5y PFS 86% |
| Optimal >60 (Pfreundschuh 2017) | Bulky (>7.5 cm) | PET-CR: no RT → 2y PFS 79% (vs 75% historical). PET+ → 39.6 Gy |
| British Columbia (Freeman Blood 2021) | Stage III–IV or I–II with B sx/bulk | R-CHOP × 6–8, PET-CR: no RT → 3y TTP 83%. PET+ RT 30–40 Gy → outcomes approach PET-neg |
Key takeaway across all 4 trials: Consolidation RT is highly effective for patients with good PR but focal residual FDG avidity — RT can rescue PET+ patients to outcomes nearly matching PET-negative. PET is the discriminator, not the stage.
POLARIX (Tilly NEJM 2022; Salles ASH 2024)
R-CHOP vs Pola-R-CHP (polatuzumab replaces vincristine) in age 18–80 with IPI 2–5. 5y PFS 63.1% vs 59.1% (HR 0.81). Pola-R-CHP is emerging alternative frontline for higher-IPI DLBCL.
DLBCL Dose Summary
| Scenario | Dose |
|---|---|
| PET-CR after full-course R-chemo | 20–30 Gy (20 Gy emerging per Kelsey 2025) |
| Partial response / residual FDG avidity | 30 Gy + 6–15 Gy boost to residual |
| Post-abbreviated chemo (<4 cycles) | 30 Gy (sometimes up to 36–40 Gy) |
Primary Mediastinal B-Cell Lymphoma (PMBCL)
- First-line: DA-EPOCH-R (preferred) or R-CHOP.
- IELSG-37 (Martelli JCO 2024): randomized ± RT after CMR to R-chemo. No PFS benefit from RT if PET-CR after 6 cycles of R-anthracycline. This trial established observation as acceptable after CMR.
- Current standard: DA-EPOCH-R × 6, no RT if PET-CR. RT reserved for PET+ residual disease.
This is the entity that Q7 on your exitthetxit sample was testing — "chemoimmunotherapy alone if complete response by PET/CT and resolution of mediastinal mass on diagnostic CT with contrast" is the IELSG-37 answer.
Primary Testicular Lymphoma
- Most common testicular tumor in men >60. High risk of CNS involvement/relapse and contralateral testis relapse.
- First-line: R-CHOP or R-Pola-CHP + CNS prophylaxis (HD-MTX).
- Prophylactic scrotal RT: 24–30 Gy (IELSG-10 established 30 Gy).
- Technique: en face electrons or photons with 1/2 cm bolus; CTV → PTV 15 mm; daily CBCT.
- Follow-up: short-term skin care; long-term serum testosterone monitoring.
Primary CNS Lymphoma
- Location: brain >80% (periventricular, deep structures), ± eye/CSF; less common: LMD, cord.
- Avoid steroids prior to biopsy — lymphoma is exquisitely steroid-sensitive and can obscure diagnosis.
- First-line: HD-MTX-based regimens — MTR (HD-MTX/temozolomide/rituximab) or R-MPV (rituximab/HD-MTX/procarbazine/vincristine).
- Consolidation options: HDT-ASCT, non-myeloablative transplant, or reduced-dose WBRT 23.4 Gy.
- RTOG 1114 (now NRG; Omuro Neuro-Onc 2026): R-MPV-A ± LD-WBRT 23.4 Gy — improved PFS with RT (HR 0.47) but trend toward more neurocognitive failure.
Extranodal NK/T-Cell Lymphoma, Nasal Type
- East Asian / South American; EBV-driven; male predominance.
- Sites: nasal cavity (most common), Waldeyer's ring (esp. nasopharynx), rarely skin/GI/lung.
- Majority early-stage, locally invasive — contrast with many other NHL subtypes.
- Workup: fiber-optic exam, PET-CT, MRI.
- Treatment: platinum- or asparaginase-based chemo (De-VIC, SMILE) + ISRT 50–54 Gy.
CTV targets (Qi IJROBP 2021):
Nasal cavity primary — whole nasal cavity + ipsilateral medial maxillary wall + anterior ethmoids + hard palate + posterior nasal aperture.
Waldeyer's ring primary — whole Waldeyer's ring + posterior nasal aperture + adjacent involved structures + uninvolved cervical nodes at prophylactic 40–45 Gy.
Nasal cavity primary — whole nasal cavity + ipsilateral medial maxillary wall + anterior ethmoids + hard palate + posterior nasal aperture.
Waldeyer's ring primary — whole Waldeyer's ring + posterior nasal aperture + adjacent involved structures + uninvolved cervical nodes at prophylactic 40–45 Gy.
PART III — CAR-T AND LYMPHOMA RADIATION
CAR-T as 2nd-Line Therapy (R/R LBCL within 12 mo)
- ZUMA-7 (Locke NEJM 2022; Westin NEJM 2023): axi-cel superior EFS and OS vs standard-of-care salvage + ASCT.
- TRANSFORM (Kamdar Lancet 2022, JCO 2025): liso-cel also superior to standard salvage.
- Together these established CAR-T as preferred 2nd-line for primary refractory or early-relapsed (<12 mo) LBCL.
CAR-T Timeline and RT Windows
Three RT windows around CAR-T:
- Emergent RT before apheresis (for disease causing symptoms/threat before T-cell collection).
- Bridging RT between apheresis and infusion — "vein-to-vein" 3+ weeks, "brain-to-vein" 8+ weeks.
- Salvage or consolidative RT after infusion (post-treatment imaging).
Bridging RT Evidence
- ILROG multicenter (Yegya-Raman Blood Adv 2025): 172 pts, 223 sites. Most common schemes: 30 Gy/10, 20 Gy/5, 20 Gy/10, 37.5 Gy/15. ORR 83%, 2y PFS 38%, 2y FFLF 80%. MVA: worse PFS with age ≥60, CNS involvement, lesion >10 cm, high LDH. Comprehensive bridging RT associated with improved OS.
- Saifi JAMA Oncol 2024: for limited disease (≤4 sites), comprehensive bridging RT improves RFS and EFS vs focal-only bridging.
Novel Bridging RT Trials
| Trial / Institution | Schema |
|---|---|
| REMIT (UK) | 20–30 Gy in 5–15 fx dominant + 4 Gy × 2 other sites (debulking + T-cell priming) |
| SC-BRT (MSKCC) | Days −12 to −8: 27 Gy/9 fx; Day −2: 3 Gy × 1 (split-course) |
| City of Hope | Comprehensive bridging to all FDG-avid sites |
| MOFFITT | Comprehensive ablative bridging to all sites ≥5 cm (high-risk R/R LBCL) |
| Nebraska | Days −20 to −7: 2 Gy × 2; post-CAR-T Days 30–80: up to 32 Gy |
| Peking Union | Post T-cell collection: 1.5 Gy BID × 10 days (ultra-fractionated) |
| MGH 5:5:5 Adaptive (Ababneh/Patel IJROBP 2025) | 5 Gy × up to 5 fractions over 5 weeks, online adaptive; 100% symptomatic response, 90% in-field response, many stopped after 1–2 fx |
Post-CAR-T RT
- Salvage RT after CAR-T failure: Three series (MSKCC, MGB/DFCI, Mayo) show LC 62–84% at median doses ~30–35 Gy. Improved outcomes with comprehensive RT for limited relapse, particularly with planned alloHSCT follow-up. MGB ICML 2025 update: 2y LPFS 71%; BED10 ≥39 Gy associated with significantly higher LPFS.
- Consolidative RT after CAR-T (Saifi Haematologica 2023): 61 pts with residual FDG activity in ≤4 sites. Consolidative RT (median EQD2 39.1 Gy; most common 37.5 Gy/15 fx) improved both PFS (p=0.025) and OS (p=0.047) vs observation.
Outcome after CAR-T failure is stratified by timing: early failure (within ~3 mo) has very poor PFS after bispecific antibody rescue; late failure (>12 mo) retains ~50% long-term PFS (Shumilov Blood Adv 2025). Timing of CAR-T failure is a prognostic variable worth remembering.
PART IV — INDOLENT NHL
Overview and Dose Foundation
- Core histologies: Follicular lymphoma (grade 1–2, 3A now grouped as "cFL"; grade 3B separately as "FLBL" per WHO 2022). Marginal zone lymphoma (extranodal/MALT, primary cutaneous, nodal). Lymphoplasmacytic, mantle cell, cutaneous follicle center.
RT dose — indolent NHL:
Lowry Rad Onc 2011: 24 Gy vs 40–45 Gy → equivalent PFS. 24 Gy became standard.
Hoskin Lancet Oncol 2021 (FoRT): 24 Gy vs 4 Gy → 5y local PFS 89.4% vs 69% (HR 3.46). 24 Gy superior for definitive intent, but 4 Gy remains a useful palliative/response-adapted option.
Lowry Rad Onc 2011: 24 Gy vs 40–45 Gy → equivalent PFS. 24 Gy became standard.
Hoskin Lancet Oncol 2021 (FoRT): 24 Gy vs 4 Gy → 5y local PFS 89.4% vs 69% (HR 3.46). 24 Gy superior for definitive intent, but 4 Gy remains a useful palliative/response-adapted option.
Response-Adapted Low-Dose RT (Imber Blood Adv 2021, ICML 2025 update)
- Give 4 Gy in 2 fractions, assess response at ~12 weeks, escalate to 20–24 Gy only if needed.
- ICML 2025 expanded cohort (281 pts limited-stage indolent NHL, 25% skin): ORR 95%, CRR 74%, only 16% needed additional RT, 5y local progression 15%, 5y out-of-field progression 22%.
Orbital Indolent B-Cell Lymphoma (Pinnix JAMA Oncol 2024)
- Phase 2, response-adapted: all get 4 Gy × 2 (ultra-low-dose); escalate to 20 Gy only if residual.
- 44/50 achieved CR with ultra-low-dose alone.
Ongoing: MSKCC NCT07029217 Phase III
Limited-stage FL (grade 1, 2, 3A) or MZL <5 cm randomized to 24 Gy/12 vs 4 Gy/1–2 with response-adapted escalation. Primary endpoint 2y PFS. Tests whether response-adapted 4 Gy can replace 24 Gy as curative-intent standard.
Candidate Algorithm for Low-Dose Response-Adapted RT
Consider low-dose response-adapted RT (4 Gy × 2 with escalation) when patient meets all:
- Limited-stage indolent lymphoma
- Sites: eye, skin, salivary glands, lungs
- Tumor <5 cm
- MZL histology (esp. MALT)
- Patient preference for de-escalation
- Reliable follow-up available
Primary Cutaneous Lymphoma Doses
| Entity | Dose |
|---|---|
| Lymphomatoid papulosis (T-cell) | Observe |
| Cutaneous T-cell / mycosis fungoides (localized) | 8 Gy |
| Primary cutaneous ALCL (pcALCL) | 4–30 Gy |
| Primary cutaneous MZL / lymphoproliferative | 4 Gy |
| Primary cutaneous follicle center lymphoma | 4 Gy |
| Primary cutaneous DLBCL, leg type | Needs immunochemotherapy (treat as aggressive NHL) |
ILROG cutaneous (Oertel Blood 2026): 535 pts pcMZL or pcFCL, median 24 Gy. 5y LC: 73% (≤4 Gy, n=57) vs 96% (>4 Gy, n=478). Informs when 4 Gy is enough vs when to escalate.
Mantle Cell Lymphoma
- t(11;14) → cyclin D1 overexpression.
- Majority presents advanced stage; treat systemically.
- Low-dose palliative RT 4 Gy → ORR 80–85% (Dabaja Ann Oncol 2017).
- Rare limited-stage presentation (predominantly H&N): RT alone ~30 Gy gives outcomes similar to chemo or CMT.
Gastric MALT Lymphoma
- H. pylori+ (majority): triple therapy (PPI + amoxicillin + clarithromycin), reassess at 4–8 weeks. 75% response rate. t(11;18)+ (30%): lower triple-therapy response rate.
- H. pylori– or triple-therapy failure: ISRT 24–30 Gy.
- 4 Gy response-adapted (Gunther Lancet Haem 2024): only 4/24 pts required dose escalation to 20 Gy.
Gastric MALT simulation pearls: NPO 4 hours before sim and each treatment; oral contrast; DIBH. CTV = whole stomach. ITV = CTV + 15 mm (organ motion). PTV = ITV + 5 mm. Assess response at 6 months post-RT (not immediate).
Emerging Hypofractionated Indolent NHL
- Wang Lancet Haematol 2025: 71 pts / 73 sites stage I–IV indolent BCL got 12 Gy in 4 fractions. 6-mo CR 95%, 18-mo LC 98.2%.
- POSEIDON (Mayo NCT06386315): Randomized 24 Gy/12 fx vs 9 Gy/3 fx (or 8 Gy/2 or 10 Gy/5) for FL/MZL/pcFCL, any stage.
CLINICAL SUMMARY ALGORITHM
| Entity | Standard |
|---|---|
| cHL early-stage favorable (GHSG) | ABVD × 2 + 20 Gy |
| cHL early-stage unfav (GHSG) / fav (EORTC) | ABVD × 3 + 30 Gy |
| cHL early unfav (GHSG/EORTC) | ABVD × 4 or BV-AVD × 4 + 30 Gy |
| cHL advanced | 6 × nivo-AVD; no RT if CR |
| R/R cHL | 2nd-line therapy → CR → ASCT; ISRT if localized R/R |
| DLBCL PET-CR | R-CHOP or R-Pola-CHP; RT if bulky ≥7.5 cm, skeletal, critical LC, or after <4 cycles abbreviated; 30 Gy (20 Gy emerging) |
| DLBCL PET+ residual | 30 Gy + 6–15 Gy boost |
| R/R LBCL (CAR-T era) | Bridging/elective 20–37.5 Gy / 4–15 fx; post-CAR-T consolidation or salvage 37.5–40 Gy / 15–20 fx |
| Indolent lymphoma | 24 Gy limited-stage curative; or low-dose response-adapted (MZL <5 cm, eye/skin/lungs/H&N) |
| NLPHL stage I or II contiguous | ISRT 24–30 Gy |
| PMBCL | DA-EPOCH-R; no RT if PET-CR (IELSG-37) |
| Testicular lymphoma | R-CHOP or R-Pola-CHP + CNS prophylaxis; scrotal RT 30 Gy |
| PCNSL | HD-MTX based (MTR or R-MPV); LD-WBRT 23.4 Gy if CR and not transplant candidate |
| NK/T nasal | Platinum/asparaginase chemo + ISRT 50–54 Gy |
| Mantle cell | 4 Gy effective palliation |
| Gastric MALT | 24 Gy, NPO 4 h pre-sim/treat, DIBH, assess response at 6 mo |
Mediastinal RT technique universal reminder: DIBH for all; in women, arms down with incline to spare breast tissue.
CROSS-CUTTING HIGH-YIELD POINTS (testable distinctions)
- Deauville 1–2 vs 1–3: de-escalation trials often use 1–2 (stricter); standard "PET-negative" clinical practice uses 1–3 (liver threshold). Know which cutoff a given trial used.
- Bulk definitions differ: HL bulky = mediastinal mass >1/3 intrathoracic diameter (MMR) or any mass ≥10 cm (or ≥7 cm per Lugano). DLBCL bulky (for consolidation indication) = ≥7.5 cm.
- NLPHL CD profile inverts cHL: CD15/30 negative, CD20 POSITIVE (that's why rituximab works in NLPHL). Classic HL: CD15/30 positive, CD20 negative.
- ESR thresholds for HL: GHSG and EORTC both use ESR ≥50 with no B sx, or ≥30 with B sx, as unfavorable.
- "Bulky" in advanced HL trials: HD0607/HD0801 allowed RT omission if PET-CR after ABVD × 6 even with initial bulk >5 cm.
- Number of nodal sites cutoff: GHSG ≥3 vs EORTC ≥4 — commonly tested.
- BM biopsy nuance: not needed for HL if PET done; still required for FL; for DLBCL only if PET does not show involvement (to find discordant histology).
- PCNSL "do NOT give steroids before biopsy" — lymphoma melts with dex and you lose the diagnosis.
- Testicular lymphoma: long-term testosterone monitoring after scrotal RT (often missed on follow-up).
- Gastric MALT DIBH + NPO 4 h — simulation pearls that are unusually testable.
KEY LANDMARK TRIALS (memorize)
| Trial | Disease | One-line takeaway |
|---|---|---|
| GHSG HD10 (Engert NEJM 2010) | Early fav cHL | ABVD × 2 + 20 Gy = ABVD × 4 + 30 Gy |
| GHSG HD11 (Eich JCO 2010) | Early unfav cHL | ABVD × 4 + 30 Gy > ABVD × 4 + 20 Gy |
| RAPID / H10 / HD16 / HD17 | Early cHL, PET-adapted | Omitting RT after PET-neg costs 3–12% PFS |
| ECHELON-1 (Ansell NEJM 2022) | Advanced cHL | BV-AVD > ABVD (6y PFS 82% vs 75%) |
| SWOG 1826 (Herrera NEJM 2024) | Advanced cHL | N-AVD > BV-AVD (2y PFS 92% vs 83%) |
| GHSG HD15 / HD18 | Advanced cHL | No RT if residual <2.5 cm or PET-neg |
| Lowry Rad Onc 2011 | Aggressive NHL | 30 Gy = 40 Gy (established 30 Gy standard) |
| Kelsey ASTRO 2025 (ILROG) | DLBCL Deauville 1–3 | 20 Gy → 3y FFLR 98.6% |
| LYSA / SWOG 1001 / Optimal >60 / BC | DLBCL PET-adapted | PET-CR: RT omission often safe; PET+: RT rescues |
| POLARIX (Tilly NEJM 2022) | DLBCL IPI 2–5 | Pola-R-CHP > R-CHOP (5y PFS 63% vs 59%) |
| IELSG-37 (Martelli JCO 2024) | PMBCL PET-CR | No PFS benefit from RT after CMR |
| RTOG 1114 (Omuro 2026) | PCNSL | R-MPV-A ± LD-WBRT 23.4 Gy; PFS benefit with RT |
| ZUMA-7 / TRANSFORM | R/R LBCL <12 mo | CAR-T (axi-cel, liso-cel) > salvage + ASCT |
| Yegya-Raman Blood Adv 2025 | Bridging RT | Comprehensive bridging RT → improved OS in pre-CAR-T |
| Saifi Haematologica 2023 | Post-CAR-T | Consolidative RT for residual FDG in ≤4 sites → PFS and OS benefit |
| Hoskin Lancet Oncol 2021 (FoRT) | Indolent NHL | 24 Gy > 4 Gy for definitive LC (89% vs 69%) |
| Pinnix JAMA Oncol 2024 | Orbital indolent BCL | Response-adapted 4 Gy × 2 → 88% CR without escalation |
| Oertel Blood 2026 | Cutaneous pcMZL/pcFCL | >4 Gy → 5y LC 96% vs 73% at ≤4 Gy |