Lymphomas and Hematologic RT - Board Review Summary

CROSS-CUTTING CONCEPTS

Staging, Workup, and Response Assessment

Lugano 2014: modifies Ann Arbor. Limited = non-bulky I-II; advanced = III-IV. Bulky I-II can behave as limited or advanced depending on histology/prognostic factors. E is only used in limited stage. X was eliminated; record maximum tumor diameter instead.
Workup: incisional/excisional biopsy preferred, never FNA alone; CBC with differential; LDH for NHL; ESR + albumin for HL; PET-CT for FDG-avid disease. Bone marrow biopsy is generally not needed for HL if PET-CT is done, still used for FL, and may be omitted for DLBCL when PET-CT already establishes marrow involvement and discordant histology is not suspected.
B symptoms: unexplained fever >38 C, drenching night sweats, or weight loss >10% body mass over 6 months. HL-associated symptoms include pruritus, fatigue, and alcohol-induced pain.
Emerging risk tools: metabolic tumor volume and circulating tumor DNA may refine future risk stratification, but Lugano stage and Deauville response remain the board-default language.

Deauville 5-point scale: 1 no uptake; 2 uptake ≤ mediastinum; 3 uptake ≤ liver; 4 moderately > liver; 5 markedly > liver or new lesions. De-escalation trials often use 1-2, while routine complete metabolic response is usually 1-3.

High-Yield Cytogenetics / Translocations

Core lymphoma and leukemia translocations that show up repeatedly on boards. Memorize the disease ↔ translocation pair and the resulting fusion partner / mechanism.

Translocation	Disease	Gene / mechanism / pearl
t(8;14)(q24;q32) (variants: t(2;8), t(8;22))	Burkitt lymphoma	MYC translocated to IGH (or IGK/IGL). Classic "starry sky" histology, Ki-67 nearly 100%, very chemo-responsive (no routine RT role).
t(14;18)(q32;q21)	Follicular lymphoma (~85%); also subset of DLBCL	BCL2-IGH; antiapoptotic. Defining FL lesion.
t(11;14)(q13;q32)	Mantle cell lymphoma; also subset (~15-20%) of multiple myeloma	CCND1-IGH → cyclin D1 overexpression. Same translocation in two different diseases — commonly tested distractor.
t(11;18)(q21;q21)	Gastric MALT lymphoma	API2-MALT1; predicts H. pylori eradication failure → favors definitive RT.
t(2;5)(p23;q35)	ALK+ Anaplastic Large Cell Lymphoma	NPM-ALK fusion. ALK+ ALCL has better prognosis than ALK- ALCL.
3q27 rearrangements (e.g., t(3;14), t(3;22))	DLBCL (especially ABC subtype); subset of FL	BCL6 rearrangement; multiple partner genes.
MYC + BCL2 and/or BCL6 rearrangements	High-grade B-cell lymphoma (HGBL), "double-hit" or "triple-hit"	Aggressive biology; CNS-risk; favors intensive systemic therapy (e.g., DA-EPOCH-R).
t(15;17)(q22;q21)	Acute promyelocytic leukemia (APL, AML M3)	PML-RARA; responsive to ATRA + arsenic trioxide. Classic non-RT trivia.
t(9;22)(q34;q11)	CML; ~20-30% of adult B-ALL ("Ph+ ALL")	BCR-ABL1 (Philadelphia chromosome). Imatinib-class TKI sensitivity.

ISRT / Response-Adapted Nomenclature

ISRT is the current practical default. Post-chemo consolidation CTV may be limited to initially involved sites adjusted for post-chemo anatomy; RT-alone CTV is more generous because RT is treating gross and microscopic disease without systemic cytoreduction.
NCTN response-adapted terminology: ISRT, RSRT, pISRT, pRSRT, and pRPRT distinguish whether pre-chemo CT, pre-chemo PET, and/or post-chemo PET shaped the target.
Extranodal ISRT: typically treat the involved organ, with important exceptions including bone, soft tissue, skin, lung, liver, and selected orbital cases. The ILROG extranodal guideline is the anchor reference for organ-specific rules.

Term	High-yield meaning
IFRT	Historical involved-field approach based on larger 2D/bony-landmark fields.
INRT	Involved-node RT. Requires ideal rad onc evaluation and pre-chemo imaging in treatment position before systemic therapy.
ISRT	Current practical standard when ideal INRT imaging is unavailable; integrates diagnostic PET/CT and anatomy.
RSRT / pISRT / pRSRT / pRPRT	Response- and PET-guided refinements. Know the terms, but do not substitute them for standard ISRT automatically.

Mediastinal setup pearl: use IV contrast and DIBH when feasible. For young women, arms-down incline/breast-board positioning with lateral breast displacement can reduce breast dose. Review heart/LV/LAD, lungs, breasts, thyroid, salivary glands, and cord; low-dose bath metrics such as lung/breast V5 can matter.

PART I - HODGKIN LYMPHOMA

Management Paradigm + Dose Anchors

Scenario	Default approach	RT / dose anchor
cHL early favorable	Combined modality remains the clean board answer; PET-adapted chemo-alone is selected-patient de-escalation with a PFS tradeoff.	ABVD x 2 -> ISRT 20 Gy / 10 fx.
cHL early unfavorable	ABVD-based combined modality is the oral-board anchor; intensified PET-adapted regimens are more systemic-therapy heavy.	ABVD x 4 -> ISRT 30 Gy / 15 fx.
cHL advanced stage III-IV	N-AVD x 6 is a modern frontline reference. Do not give routine RT after complete metabolic response.	RT only for residual PET-positive, symptomatic, threatening, or selected bulky/residual sites; often 30-36 Gy.
R/R cHL, transplant-eligible	Salvage systemic therapy -> ASCT; add RT for localized relapse, bulky ≥5 cm, incomplete response, or morbidity-prevention sites.	Typical peri-transplant ISRT 30-36 Gy; gross refractory/residual may need 36-45 Gy.
NLPHL / NLPBL	Stage IA/IIA non-bulky contiguous disease can be treated with RT alone; higher-risk/noncontiguous disease often uses systemic or combined modality therapy.	Generous ISRT, usually 30 Gy.
Palliation / urgent local control	Use local RT for cord/SVC/airway/nerve-root/GI-GU obstruction, pain, or bleeding.	20 Gy / 5 fx or 30 Gy / 10 fx, individualized to prior RT and intent.

Pathology (WHO/ICC 2022)

Classical HL, about 95%: CD15+, CD30+, CD20-. Subtypes include nodular sclerosis, mixed cellularity, lymphocyte-rich, and lymphocyte-depleted.
NLPHL / nodular lymphocyte predominant B-cell lymphoma: CD15-, CD30-, CD20+. Behaves more like indolent B-cell lymphoma; re-biopsy relapse to rule out transformation to DLBCL.

Limited-Stage HL Prognostic Factors

Factor	GHSG unfavorable if any	EORTC unfavorable if any
Age	-	≥50
ESR / B symptoms	ESR ≥50, or ≥30 with B symptoms	ESR ≥50, or ≥30 with B symptoms
Large mediastinal adenopathy	MMR >1/3	MTR >0.35
Extranodal sites	Any E site	-
Number of nodal sites	≥3	≥4

Early-Stage cHL Management

Risk / trial	Arm	Outcome / takeaway
Favorable	HD10 / HD16 anchor: ABVD x 2 -> ISRT/IFRT 20 Gy	Canonical combined-modality board answer.
Favorable PET-adapted	RAPID, H10F, HD16: omit RT if PET-negative after ABVD	Omitting RT after PET-negative response costs PFS, with little OS effect.
CALGB 50604	Non-bulky early HL; ABVD x 4 alone if interim PET2 negative	Useful selected chemo-alone option, but not randomized against CMT.
Unfavorable	HD11: ABVD x 4 -> ISRT 30 Gy	20 Gy after ABVD could not be proven non-inferior; 30 Gy remains the board anchor.
Unfavorable PET-adapted	H10U: ABVD x 4 + INRT/ISRT 30 Gy vs ABVD x 6	Supports abbreviated chemo + RT for early unfavorable disease.
GHSG HD17	eBEACOPP x 2 + ABVD x 2 -> omit RT if PET-negative	Excellent PFS, but with more intensive systemic therapy.

Early cHL bottom line: combined-modality therapy remains the most reliable board-review answer. PET-adapted omission of RT is reasonable for selected patients, but it trades away some PFS; relapses after RT omission commonly involve initially involved sites.

Evolving early unfavorable cHL regimens: BV-AVD and N-AVD/nivo-AVD are active bleomycin-sparing approaches under study or selected use. For board review, know the names but anchor management to the randomized combined-modality data.

Advanced cHL Management

Trial	Regimen	PFS / takeaway
ECHELON-1	BV-AVD vs ABVD	Long-term PFS and OS favored BV-AVD.
SWOG S1826	N-AVD vs BV-AVD	N-AVD improved PFS and is a frontline reference for stage III-IV cHL.
RATHL	ABVD x 2, drop bleomycin if PET2-negative	AVD after PET2 CR preserves efficacy and reduces pulmonary toxicity.
GHSG HD15 / HD18	eBEACOPP with PET-adapted consolidation	No RT if residual <2.5 cm or PET-negative.
HD0607 / HD0801	ABVD x 6; bulky PET-CR sites randomized to RT vs no RT	RT omission is safe when PET-CR follows full chemotherapy.

Advanced cHL practical rule: with modern N-AVD, RT is not routine after complete metabolic response. RT remains individualized for residual PET-positive, symptomatic, or threatening sites.

R/R cHL

Standard: second-line therapy such as BV-Nivo, ICE, P-GVD, or other salvage regimens -> ASCT when transplant-eligible.
RT role: localized relapse encompassable by reasonable fields, bulky site ≥5 cm, incomplete response to reinduction, or sites where local control prevents serious morbidity such as cord, SVC, nerve root, airway, GU, or GI obstruction.
Selected low-risk transplant-free approaches: BV/Nivo + ISRT and pediatric/AYA response-adapted strategies may avoid ASCT in carefully selected patients.

NLPHL / Nodular Lymphocyte Predominant B-Cell Lymphoma

Male predominance, peripheral nodal presentation, CD20+, late relapse pattern.
Stage IA/IIA non-bulky contiguous: ISRT 30 Gy alone is a classic option. Use a more generous involved-site CTV than post-chemo cHL because RT alone is treating possible microscopic extension.
All other limited-stage presentations may need combined modality therapy or systemic therapy depending on extent and clinical risk.

Mediastinal HL RT technique: DIBH reduces heart, LV, LAD, and often lung dose. In women, arms down with incline can reduce breast dose. Common planning goals include mean heart <5-8 Gy, LV mean <8 Gy, LAD V15 <10%, lung mean ≤13.5 Gy, lung V20 <20% if feasible, thyroid V25 <63.5%, and breast dose ALARA.

PART II - AGGRESSIVE NON-HODGKIN LYMPHOMA

Management Paradigm + Dose Anchors

Entity / scenario	Default approach	RT / dose anchor
Limited-stage non-bulky low-risk DLBCL	R-CHOP-based therapy with PET-adapted omission of RT in selected low-risk patients; RT remains favored if chemo is abbreviated or local risk is high.	30 Gy established after CR; 20 Gy emerging after full chemo + Deauville 1-3.
Bulky, osseous, high-risk limited, or critical-site DLBCL	Full systemic therapy such as R-CHOP or Pola-R-CHP depending risk; consolidate sites where local failure is consequential.	CR: 30 Gy; PR/PET+ residual: 30 Gy + 6-15 Gy boost or 36-45 Gy.
Advanced-stage DLBCL	Systemic therapy drives cure; RT is selective for bulky, osseous, residual PET-positive, or morbidity-prevention sites.	Same consolidation logic: 30 Gy after CR; higher for residual FDG-avid disease.
PMBCL	DA-EPOCH-R commonly preferred. If Deauville 1-3 complete metabolic response, omit mediastinal RT; biopsy or individualize Deauville 4-5.	If RT needed: often 30-36 Gy; salvage/refractory mediastinum may require 36-45 Gy.
Primary testicular DLBCL	Radical inguinal orchiectomy + R-CHOP-based systemic therapy + CNS prophylaxis + contralateral testis RT.	Intact testis/scrotal contents 25-30 Gy; stage II nodal sites may receive ISRT by response.
Primary breast DLBCL	R-CHOP-based systemic therapy; consider CNS-risk discussion and ipsilateral breast/chest wall RT for local control.	30-36 Gy to involved breast/chest wall region after chemo response.
Primary orbital / lacrimal-gland DLBCL	Combined modality, NOT RT alone. R-CHOP-based systemic therapy + ISRT. Distinguish from indolent orbital MALT/FL, which is often curable with RT alone.	Stage IAE typically R-CHOP x 3 + ISRT 30 Gy; abbreviated chemo + RT also acceptable per modern PET-adapted limited-stage logic.
Primary CNS lymphoma	HD-MTX-based induction; consolidation with ASCT, non-myeloablative therapy, or reduced-dose WBRT depending fitness/response.	CR consolidation WBRT option 23.4 Gy / 13 fx; salvage WBRT 24-30 Gy +/- boost to 45 Gy.
Extranodal NK/T nasal type	Asparaginase- or platinum-based chemotherapy plus definitive involved-site RT.	50-54 Gy; avoid underdosing below 50 Gy for definitive intent.

DLBCL: Workup, Pathology, and Risk Labels

Workup: excisional biopsy preferred; core acceptable if diagnostic. Include H&P with B symptoms and PS, nodal/spleen/liver/Waldeyer exam, CBC with differential, LDH, LFTs, HIV, hepatitis B, pregnancy test when applicable, contrasted PET/CT, echo, and fertility referral when relevant.
Pathology: DLBCL is typically CD20+, CD45+, CD3-. Ki-67 is often high. Hans algorithm separates GCB from non-GCB by CD10, BCL6, and MUM1.
Double-hit vs double-expressor: MYC rearrangement with BCL2 and/or BCL6 rearrangement is high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements; double-expressor is protein overexpression without those defining translocations.
CNS-risk assessment: consider LP and CNS prophylaxis for testicular, PCNSL/secondary CNS risk, breast, leg-type DLBCL, double/triple-hit disease, kidney/adrenal involvement, or high CNS-IPI.

IPI / aa-IPI

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

Limited-stage DLBCL risk label: stage-modified IPI helps separate limited non-bulky low-risk disease from bulky or higher-risk limited-stage disease. Bulky disease is commonly ≥7.5 cm for DLBCL consolidation decisions.

Dose Escalation / De-escalation

Lowry: 30 Gy / 15 fx vs 40-45 Gy in aggressive NHL showed no difference in LC, PFS, or OS. This established 30 Gy as the standard consolidation dose after CR to chemotherapy.

ILROG phase II 20 Gy concept: PET-CR aggressive B-cell lymphoma treated with about 20 Gy has excellent early local control. This supports 20 Gy as an emerging option after full chemoimmunotherapy and Deauville 1-3 response; 30 Gy remains the most established board standard.

Indications for Consolidation RT

Bulky disease ≥7.5 cm
Skeletal site involvement, especially dominant osseous disease
Critical local-control sites: cord/nerve root compression, bleeding, airway or GI/GU obstruction
Limited stage treated with abbreviated chemo (<4 cycles full-dose R-chemo)
Incomplete response or focal residual FDG avidity after systemic therapy

PET-Response-Adapted DLBCL Trials

Trial	Population	Key finding
LYSA	Limited, non-bulky (<7 cm)	PET-CR after R-CHOP-14 x 4: RT omission non-inferior in selected low-risk patients.
SWOG S1001	Limited, non-bulky (<10 cm)	R-CHOP x 3 + PET; if CR, one more cycle and no RT; PET+ patients received RT-based intensification.
OPTIMAL >60	Bulky >7.5 cm	PET-CR patients observed; PET+ patients treated with RT.
British Columbia	Advanced or high-risk limited disease	PET+ residual sites treated with RT had outcomes approaching PET-negative patients.

Key takeaway: PET response is the discriminator. RT is most valuable for focal residual PET-positive disease, bulky sites, osseous disease, or when chemo is abbreviated.

POLARIX

R-CHOP vs Pola-R-CHP: age 18-80 with IPI 2-5. PFS favored Pola-R-CHP, making it a frontline option for higher-risk DLBCL; RT principles remain driven by bulk, site, response, and local-control need.

DLBCL Dose Summary

Scenario	Dose
PET-CR after complete R-chemo	30 Gy established; 20 Gy emerging in selected Deauville 1-3 patients
Partial response / residual FDG avidity	30 Gy + 6-15 Gy boost to residual disease
Post-abbreviated chemo (<4 cycles)	30 Gy, sometimes 36-40 Gy depending on response and risk

Primary Mediastinal B-Cell Lymphoma

Thymic B-cell origin; clinicopathologically closer to cHL than typical DLBCL. Female predominance, young adult age, bulky anterior mediastinal disease, and SVC symptoms are common.

First-line: DA-EPOCH-R is commonly preferred; R-CHOP-based treatment is also used in some settings.
IELSG37: mediastinal RT may be omitted after anthracycline/rituximab-containing immunochemotherapy when the patient achieves complete metabolic response, defined as Deauville 1-3.
Important PET caveat: PMBCL has a high false-positive PET rate. Deauville 4-5 residual uptake should prompt biopsy if feasible or individualized RT/salvage decisions rather than automatic escalation.

Correct framing: residual mediastinal mass on CT is not the same thing as active disease. The key management label is metabolic response, especially Deauville 1-3 vs 4-5.

Primary Testicular Lymphoma

Most common testicular tumor in men >60; high risk of contralateral testis relapse and CNS relapse.
Initial management: radical inguinal orchiectomy for diagnosis and local control.
Staging/workup: standard DLBCL workup plus MRI brain and LP because CNS risk drives management.
IELSG-10 approach: R-CHOP-based systemic therapy, CNS prophylaxis, and prophylactic RT to the contralateral/intact testis.
RT dose/technique: 25-30 Gy to the intact testis/scrotal contents; IELSG-10 used 30 Gy. Common setup: frog-leg or similar immobilization, electrons or photons with bolus as needed, penis displaced out of field, and daily image guidance.
Follow-up: monitor testosterone and consider endocrine support.

Primary Orbital and Ocular DLBCL

Pathology drives management. The orbital region hosts both indolent and aggressive lymphomas, and their treatment paradigms differ fundamentally.

Anatomic site / scenario	Most common histology	Treatment paradigm
Orbital adnexa (lacrimal gland, conjunctiva, eyelid, soft tissue, extraocular muscles)	~75-80% MALT lymphoma (indolent); ~5-10% DLBCL; smaller fractions FL and other.	Histology-driven: indolent → RT alone curative-intent (see PART IV orbital section); DLBCL → combined modality.
Intraocular / vitreoretinal lymphoma	Nearly always DLBCL; frequently associated with or precedes PCNSL.	Treat per PCNSL paradigm: HD-MTX-based induction +/- ocular RT or consolidation WBRT. CSF and brain MRI workup mandatory.

Stage IAE orbital / lacrimal-gland DLBCL: the typical board answer is R-CHOP x 3 + ISRT 30 Gy (combined modality), NOT RT alone. RT alone is reserved for indolent orbital lymphoma (MALT/FL). Abbreviated chemo + RT is well-supported by limited-stage DLBCL trials, and short-course chemo helps reduce the local field/dose burden near optic structures.

Common board trap: stage IAE orbital lymphoma in an older patient. The reflex answer of "RT alone 24 Gy" is correct for MALT but wrong for DLBCL. Always confirm pathology before locking in the management plan.

Planning pearl: for orbital DLBCL, ISRT typically covers the involved orbital compartment with anatomic respect for the contralateral eye, optic chiasm, brain, and lens. Lens-sparing techniques and IMRT/proton consideration are common when lacrimal gland or anterior orbit is the target.

Primary CNS Lymphoma

Usually deep/periventricular brain disease; can involve eye, CSF, leptomeninges, or spinal cord.
Avoid steroids before biopsy when safe because lymphoma is steroid-sensitive and diagnosis can disappear.
First-line: HD-MTX-based regimens such as R-MPV or MTR; consolidation options include HDT-ASCT, non-myeloablative therapy, or reduced-dose WBRT.
RTOG 1114 / NRG: R-MPV-A with 23.4 Gy low-dose WBRT improved PFS vs chemoimmunotherapy alone, with favorable reported neurocognitive outcomes; OS difference was not statistically significant.
RT fields: whole brain plus upper 1-2 cervical vertebral bodies and posterior orbit; include both eyes if ocular involvement.
Salvage RT: WBRT 24-30 Gy with boost to residual disease up to about 45 Gy.

Extranodal NK/T-Cell Lymphoma, Nasal Type

EBV-driven; East Asian and South American predominance; commonly presents as early-stage but locally invasive nasal disease.
Workup: fiber-optic exam, PET-CT, and MRI/contrasted CT to define local extent.
Treatment: platinum- or asparaginase-based chemotherapy plus ISRT 50-54 Gy. Dose should generally be at least 50 Gy for definitive treatment.

Nasal NK/T CTV rules: limited unilateral anterior/mid nasal disease covers bilateral nasal cavity, ipsilateral maxillary sinus, bilateral anterior ethmoids, and hard palate. Bilateral nasal involvement includes bilateral maxillary sinuses. Posterior aperture/nasopharyngeal extension includes nasopharynx; anterior ethmoid extension should include posterior ethmoids; adjacent organ or cervical nodal involvement should be included when involved.

PART III - CAR-T AND LYMPHOMA RADIATION

Management Paradigm + Dose Anchors

Window	Use case	Dose anchor
Before apheresis	Only for emergent organ-threatening symptoms when waiting is unsafe; avoid compromising collection when possible.	8 Gy x 1, 20 Gy / 5 fx, or tailored urgent RT.
Bridging after apheresis, before infusion	Best-planned RT window. Treat dominant symptomatic sites, all active sites if limited-volume and safe, or bulky chemoresistant sites.	20 Gy / 5 fx, 20 Gy / 10 fx, 30 Gy / 10 fx, 36 Gy / 12 fx, or 37.5 Gy / 15 fx.
Post-CAR-T residual disease	Consider for limited persistent FDG-avid disease when all active sites are encompassable and marrow/OAR constraints are acceptable.	Often salvage-like 30-36 Gy; escalate for gross refractory disease if safe.
Late limited relapse after CAR-T	More salvageable than very early failure; use RT when durable local control is realistic or symptoms threaten function.	Site- and intent-based: 20 Gy / 5 fx, 30 Gy / 10 fx, or definitive/salvage dosing.

CAR-T as Second-Line Therapy for Early R/R LBCL

ZUMA-7: axi-cel superior to standard salvage + ASCT for primary refractory or early-relapsed LBCL.
TRANSFORM: liso-cel also superior to standard salvage in the same clinical space.

CAR-T Timeline and RT Windows

Emergent RT before apheresis for immediate organ-threatening symptoms.
Bridging RT between apheresis and infusion; vein-to-vein timing is often 3+ weeks.
Post-CAR-T RT as salvage or consolidation for limited residual/progressive sites.

Bridging workflow pearl: when CAR-T is planned, simulate before apheresis when feasible and treat between apheresis and infusion if bridging RT is needed. A practical split is 20 Gy / 5 for rapid symptom control or widespread disease when only a dominant site is treated, versus salvage-like 36 Gy / 12 when isolated disease is otherwise controlled. Keep CTV lean when treatment can start quickly, and watch marrow reserve, circulating blood dose, and lymphopenia from broad low-dose bath.

Bridging / Post-CAR-T RT

Common bridging schedules include 20 Gy / 5, 20 Gy / 10, 30 Gy / 10, and 37.5 Gy / 15, tailored to urgency, marrow reserve, prior RT, and disease bulk.
Comprehensive bridging to all active sites appears better than focal-only bridging in limited-volume disease, but field size must be balanced against lymphopenia, toxicity, and logistics.
Post-CAR-T consolidation/salvage RT is most compelling for limited residual FDG-avid disease or limited relapse where all active sites can be encompassed.

Timing of CAR-T failure matters: very early failure has poor outcomes; late relapse after CAR-T is more salvageable. This timing should shape the aggressiveness of salvage RT/systemic strategies.

PART IV - INDOLENT NHL AND OTHER HEMATOLOGIC RT

Management Paradigm + Dose Anchors

Entity / scenario	Default approach	RT / dose anchor
Limited-stage FL / MZL / indolent B-cell NHL	Definitive RT alone is curative-intent for stage I or contiguous stage II disease; use a more generous ISRT volume than post-chemo lymphoma.	24 Gy / 12 fx.
Very-low-dose / response-adapted indolent RT	Useful for palliation or selected de-escalation-friendly sites with reliable reassessment.	4 Gy / 2 fx then reassess; escalate to 20-24 Gy if residual disease.
Orbital adnexal MALT / FL	Definitive conventional RT or response-adapted ultra-low-dose RT depending size, symptoms, and follow-up reliability. For orbital DLBCL, see PART II.	Conventional 24-25 Gy; response-adapted start 4 Gy / 2 fx.
Gastric MALT	H. pylori eradication first if positive; RT for negative, persistent, progressive, symptomatic, or t(11;18)-associated disease.	24-30 Gy to whole stomach + involved nodes; manage stomach filling/motion.
Primary cutaneous lymphoma	Local RT for symptomatic/localized lesions; match dose to histology and durability goal.	MF/CTCL often 8 Gy / 2 fx; pcALCL 20-30 Gy; pcMZL/pcFCL 24 Gy definitive.
Mantle cell lymphoma	Usually systemic therapy; rare localized presentations may receive ISRT, and palliation can be very low dose.	Localized 24-30 Gy; palliation 4 Gy / 2 fx.
Solitary plasmacytoma	Rule out myeloma first; definitive RT gives high local control.	35-40 Gy if <5 cm; 40-50 Gy if ≥5 cm or higher-risk site.
Myeloma / chloroma / leukemic disease / TBI	RT is palliative, local-control, CNS-directed, sanctuary-site (testes), or conditioning-based depending disease context.	Myeloma 20 Gy / 8 fx; chloroma 24 Gy / 12 fx; CNS leukemia CSI ~23.4 Gy / 13 fx; testicular relapse in B-ALL 24 Gy; TBI often 12-13.2 Gy fractionated.

Indolent NHL Dose Foundation

Core histologies: follicular lymphoma grade 1-2 and 3A, marginal zone/MALT lymphoma, lymphoplasmacytic lymphoma, mantle cell lymphoma, and cutaneous follicle center lymphoma.
Follicular pathology update: WHO/ICC 2022-era language is moving away from the old grade 1/2/3A/3B shorthand toward classic follicular lymphoma vs follicular large B-cell lymphoma. For RT boards, grade 1-2/3A or classic FL behaves as indolent; 3B/large B-cell biology should be managed like aggressive lymphoma.

Lowry: 24 Gy was equivalent to 40-45 Gy for indolent NHL, establishing 24 Gy as the curative-intent standard. FoRT: 24 Gy was superior to 4 Gy for durable local control, but 4 Gy remains useful for palliation and response-adapted strategies.

Limited-Stage Follicular / Marginal Zone Lymphoma

Definitive standard: 24 Gy / 12 fx for stage I or contiguous stage II low-grade FL/MZL.
RT-alone volume: use a generous involved-site approach because no systemic therapy is planned.
Response-adapted low-dose RT: 4 Gy / 2 fx followed by response assessment and escalation to 20-24 Gy only if needed is most attractive for small-volume, reliable-follow-up, de-escalation-friendly scenarios such as orbit, skin, salivary gland, lung, and MALT histology.

Orbital Indolent B-Cell Lymphoma (MALT / FL)

Histology check first: the orbital adnexa hosts predominantly MALT lymphoma (~75-80%) and smaller fractions of FL and DLBCL. This section applies only to indolent orbital lymphoma. Orbital DLBCL is NOT treated with RT alone — see PART II for combined modality management (R-CHOP-based therapy + ISRT 30 Gy).

Definitive conventional approach: 24-25 Gy, minimizing lens, lacrimal gland, retina, optic nerve, and brain dose.
Response-adapted ultra-low-dose approach: start with 4 Gy / 2 fx, reassess at about 12 weeks, and escalate to about 20 Gy only if residual disease persists.
Typical target for orbital MALT/FL is the involved orbital compartment; whole-orbit fields are used when disease extent or multifocality warrants.

Primary Cutaneous Lymphoma Doses

Entity	Dose / approach
Lymphomatoid papulosis	Observe when asymptomatic; local RT only for selected persistent symptomatic lesions.
Localized mycosis fungoides / CTCL	8 Gy / 2 fx is useful; 4-12 Gy can be used depending on intent and lesion context.
Primary cutaneous ALCL	20-30 Gy conventional definitive; lower doses may palliate.
Primary cutaneous MZL / follicle center lymphoma	24 Gy established for durable definitive control; 4 Gy is best framed as palliative or response-adapted with readiness to escalate.
Diffuse mycosis fungoides / Sezary syndrome	Total skin electron therapy can be used for diffuse symptomatic skin disease; low-dose 12 Gy is common for palliation/repeatability, while 30-36 Gy is reserved for selected durable-control scenarios.
Primary cutaneous DLBCL, leg type	Treat as aggressive NHL with systemic therapy +/- RT.

Cutaneous B-cell caution: very-low-dose RT can work, but current data suggest ≤4 Gy has less durable local control than higher-dose RT for definitive pcMZL/pcFCL. Avoid presenting 4 Gy as the universal curative dose.

Gastric MALT Lymphoma

H. pylori positive: treat with eradication therapy first; lymphoma regression occurs in most responders but can take months.
t(11;18) predicts lower antibiotic response.
H. pylori negative, persistent, progressive, or symptomatic disease: 24-30 Gy ISRT is standard. Response-adapted 4 Gy / 2 fx with escalation is promising but selective.

Gastric MALT planning: NPO before simulation and treatment; use oral contrast as appropriate; manage motion with DIBH or 4DCT. CTV = whole stomach + involved nodes. ITV accounts for motion; PTV commonly ITV + 1-1.5 cm. Use daily CBCT to check stomach filling/coverage and resim if reproducibility is poor. Assess response months later, not immediately.

Mantle Cell Lymphoma

t(11;14) leads to cyclin D1 overexpression.
Most patients present with advanced disease and need systemic therapy.
Rare contiguous stage I-II presentations can be treated with ISRT around 24-30 Gy; 30 Gy is a practical board anchor.
For palliation, mantle cell lymphoma is very radiosensitive; 4 Gy / 2 fx can produce high response rates.

Plasma Cell Neoplasms and Leukemia RT

CRAB-SLM features must be excluded before diagnosing solitary plasmacytoma.
Solitary plasmacytoma: local control 85-90% with RT. Typical dose 40-50 Gy; consider 35-40 Gy for lesions <5 cm and 40-50 Gy for lesions ≥5 cm. CTV expansion is often 0.5-2 cm, respecting anatomy.
Multiple myeloma: RT is used for palliation of painful lesions, fracture risk, cord compression, or postoperative sites. 20 Gy / 8 fx is a common palliative regimen.
Chloroma / myeloid sarcoma: RT gives excellent palliation/local control; at least 20 Gy is typical, with 24 Gy / 12 fx a common regimen.
CNS leukemia (CSI): craniospinal irradiation around 23.4 Gy / 13 fx is a classic reference dose when CSI is indicated.
CNS-directed RT in ALL: 18 Gy is used for CNS3 disease or cranial-nerve involvement at presentation or persisting after induction.
Testicular relapse in B-cell ALL: after induction therapy, residual testicular disease should receive RT, as systemic therapy alone is typically insufficient for this sanctuary site. NCCN-recommended conventional dose: 24 Gy. Setup similar to primary testicular DLBCL (frog-leg, photons or electrons with bolus, penis displaced from field, daily IGRT). Follow testosterone after RT.
TBI for transplant conditioning: fractionated 12-13.2 Gy, up to about 14.4 Gy by regimen, is a classic ALL/HSCT reference; regimen and organ shielding are treatment-plan specific.

Testicular sanctuary-site principle: the blood-testis barrier shields testicular disease from many systemic agents. This is why any residual testicular disease after induction in ALL or any primary testicular DLBCL warrants directed RT. The blood-testis barrier concept also justifies prophylactic contralateral testis RT in primary testicular DLBCL (IELSG-10).

CLINICAL SUMMARY ALGORITHM

Entity	Standard / practical board answer
cHL early favorable	ABVD x 2 + 20 Gy; selected PET2-negative non-bulky patients may omit RT after more chemo with PFS tradeoff.
cHL early unfavorable	ABVD x 4 + 30 Gy; know H10U/HD11 rationale.
cHL advanced	N-AVD x 6 is a frontline reference; no routine RT if PET-CR.
NLPHL IA/IIA contiguous	Generous ISRT alone, usually 30 Gy.
DLBCL PET-CR	R-CHOP or Pola-R-CHP; RT if bulky ≥7.5 cm, osseous, critical local control, abbreviated chemo, or residual risk. 30 Gy established; 20 Gy emerging after complete chemo/PET-CR.
DLBCL PET+ residual	30 Gy + 6-15 Gy boost to residual disease.
PMBCL	DA-EPOCH-R; omit RT if CMR; biopsy or individualize Deauville 4-5.
Primary testicular DLBCL	Orchiectomy + R-CHOP + CNS prophylaxis + contralateral testis RT 25-30 Gy.
Primary breast DLBCL	R-CHOP-based therapy + ipsilateral breast/chest wall RT 30-36 Gy; consider CNS-risk discussion.
Primary orbital / lacrimal DLBCL	R-CHOP x 3-6 + ISRT 30 Gy; do NOT treat with RT alone.
PCNSL	HD-MTX-based therapy; reduced-dose WBRT 23.4 Gy is an active consolidation option.
NK/T nasal	Platinum/asparaginase chemotherapy + ISRT 50-54 Gy.
Indolent FL/MZL (incl. orbital MALT)	24 Gy definitive; selected low-dose response-adapted 4 Gy with escalation.
Gastric MALT	H. pylori eradication first if positive; RT 24-30 Gy for negative/persistent/progressive disease.
Solitary plasmacytoma	Rule out myeloma; RT 40-50 Gy depending on size/site.
Testicular relapse in B-ALL	RT 24 Gy to residual disease post-induction (NCCN); 18 Gy for CNS3/cranial-nerve disease.

CROSS-CUTTING HIGH-YIELD POINTS

Deauville 1-2 vs 1-3: 1-2 is stricter and often used for de-escalation trials; 1-3 is the usual complete metabolic response threshold.
ISRT is the default field language: INRT requires ideal pre-chemo treatment-position imaging; RSRT/pISRT/pRSRT/pRPRT are selected protocol refinements.
Translocation high-yields: t(8;14) Burkitt (MYC); t(14;18) FL (BCL2); t(11;14) MCL and some MM (cyclin D1); t(11;18) gastric MALT (API2-MALT1); t(2;5) ALK+ ALCL (NPM-ALK).
Early cHL: omitting RT after PET-negative response costs PFS; combined-modality therapy remains the cleanest board answer.
Unfavorable cHL: GHSG and EORTC differ: nodal-site cutoff GHSG ≥3 vs EORTC ≥4; EORTC includes age ≥50.
DLBCL: stage-modified IPI and bulk determine whether abbreviated chemo/no RT is appropriate.
PMBCL: Deauville 1-3 CMR, not mass disappearance, is the key label for omitting RT.
Testicular lymphoma: think orchiectomy, CNS prophylaxis, contralateral testis RT, and testosterone monitoring.
Primary breast DLBCL: treat as aggressive B-cell lymphoma with systemic therapy plus ipsilateral breast/chest wall RT for local control; remember CNS-risk discussion.
Orbital lymphoma trap: orbital adnexal disease is mostly MALT (RT alone ~24 Gy works), but orbital DLBCL = combined modality with R-CHOP + ISRT 30 Gy. Intraocular/vitreoretinal lymphoma is usually DLBCL and behaves like PCNSL.
Gastric MALT: H. pylori-positive disease may regress slowly after eradication; t(11;18) predicts lower response.
Cutaneous B-cell lymphoma: 4 Gy is useful, but not always durable enough for definitive intent.
CAR-T RT timing: sim before apheresis if feasible; most planned bridging happens after collection and before infusion, with dose/volume balanced against marrow and lymphocyte toxicity.
Plasmacytoma: rule out myeloma with CRAB-SLM and marrow/systemic workup before definitive RT.
Sanctuary sites in B-ALL: testicular relapse post-induction gets 24 Gy (NCCN); CNS3 disease or cranial-nerve involvement gets 18 Gy CNS-directed RT.

KEY LANDMARK TRIALS

Trial	Disease	One-line takeaway
Lugano 2014	Staging/response	Modern lymphoma staging and Deauville response framework.
ILROG ISRT	RT volumes	Modern involved-site RT volume principles.
GHSG HD10 / HD16	Early favorable cHL	ABVD x 2 + 20 Gy is foundational; PET-negative omission lowers PFS.
RAPID / H10	Early HL PET-adapted	Omitting RT after PET-negative response lowers PFS.
CALGB 50604	Non-bulky early HL	ABVD x 4 alone is a selected PET2-negative chemo-alone option.
GHSG HD11 / HD17	Early unfavorable cHL	ABVD x 4 + 30 Gy remains a standard CMT answer; HD17 is intensive PET-adapted omission.
ECHELON-1	Advanced cHL	BV-AVD improved PFS and OS vs ABVD.
SWOG S1826	Advanced cHL	N-AVD improved PFS and tolerability vs BV-AVD.
Lowry	NHL dose	30 Gy for aggressive NHL CR; 24 Gy for indolent NHL.
S1001 / LYSA / FLYER	Limited-stage DLBCL	Define selected groups where RT can be omitted after adequate chemo/PET-CR.
POLARIX	Higher-risk DLBCL	Pola-R-CHP improves PFS vs R-CHOP.
IELSG37	PMBCL CMR	RT can be omitted after Deauville 1-3 CMR.
IELSG-10	Primary testicular DLBCL	Systemic therapy + CNS prophylaxis + contralateral testis RT prevents testicular relapse.
RTOG 1114	PCNSL	Low-dose WBRT 23.4 Gy improves PFS after R-MPV-A.
ZUMA-7 / TRANSFORM	Early R/R LBCL	CAR-T beats standard salvage + ASCT in early relapse/refractory disease.
FoRT	Indolent NHL	24 Gy gives more durable LC than 4 Gy for definitive intent.
Pinnix orbital response-adapted RT	Orbital indolent BCL	4 Gy x 2 with selective escalation produces high CR rates.
Gunther gastric MALT	Gastric MALT	4 Gy response-adapted RT is promising but selective.
ILROG plasmacytoma	Solitary plasmacytoma	Definitive RT gives high LC; dose depends on size/site.
ILROG TBI	Transplant conditioning	Fractionation, dose rate, technique, and shielding are regimen-specific.