Management of Gastric Lymphoma

withRadiation Therapy

Dr. V . Lokesh M.D.Associate Professor

Dept of Radiation Oncology, KMIO, Bangalore 29

GASTRIC LYMPHOMA• Primary gastric lymphoma is rare however, the incidence of this

malignancy is increasing.

• Any portion of GI tract can be involved with systemic NHL

• Gastric Lymphoma is the most common extranodal site (50-60%)

• Arise from B cells of mucosa-associated lymphoid tissue (MALT)

• <15%of gastric malignancies and 2%of all lymphomas

GASTRIC LYMPHOMA

• MALT lymphomas arise in the setting of mucosal lymphoid activation due to H. pylori infection

• HP causes activation of T and B cells leading to B cell hyperplasia and the emergence of a monoclonal B cell population

• Primary GI lymphomas are amenable to treatment

Major histological subtypes of gastric lymphoma

Low- grade GL:

• Low- grade B cell lymphoma of MALT

(approximately 45% of cases).

Histologically aggressive GL:

• Diffuse large B- cell lymphoma

(approximately 45% of cases).

Stage

IE Lymphoma limited to the stomach

IIE1

Involvement of stomach and contiguous lymph nodes

(Peri-gastric area / Level L1 – L2)

IIE2 Involvement of stomach and noncontiguous

　 subdiaphragmatic lymph nodes(L3 downwards or in mesentry)

IIIInvolvement of stomach and lymph nodes on

both sides of diaphragm

Indications for Radiation Therapy (Ann Arbor, modified by Musshoff)

MALT – RT indications

• H pylori +ve (endoscopy / CT)

– response : 35 – 100%

– Eradicated in 85 - 90%

– 30-50% will show persistent or progression even after eradication

– 15% relapse within 3years of CR

• H pylori –veContn ..

• H pylori +ve :– show markedly decreased response when– node +ve– penetration beyond mucosa– distal part of stomach– with high grade component – Chromosomal translocation t(11;18)(q21;q21)

~25% superficial • 67% non responders• t(11;18) –ve have a higher risk of transformation to

diffuse B-cell – incomplete regression – closely monitored – therapeutic alternatives

RT - Treatment Intent

• Radical - localized NHL (treated with curative intent).

• Palliative - used when condition of the patient, the extent and location of disease, or the nature of the disease, a radical treatment offers no opportunity for cure.

• RT alone : Stage I E , MALT• radiotherapy is used as an adjuvant to surgery,

chemotherapy or both• CT RT : aggressive lymphomas all stages• Post OP RT / Bx: as adjuvant

– potentially curative resections. – Incomplete resection– Margin + ve– Multifocal disease– Penetration of bowel wall stage I : microscopic (R1) or macroscopic (R2) stage II disease: (R0), R1 or R2 resection

Radiation Therapy Sequencing

RT TechniquesAim of RT : homogeneous distribution of irradiation dose

within the target area.

Current irradiation techniques :Use Simulators, Computer Planning System to custom-designed fields that conform to the individual patient's anatomy and tumor location

Techniques • parallel opposed fields AP:PA • three or four-field

use of beam-modifying devices - shields - Compensators- Patient immobilizing devices

Radiation Therapy - treatment plan takes into consideration • all staging data• normal anatomical structures in the vicinity• common routes of lymphatic spread• appreciation of the radiation therapy tolerance of normal

organs and tissues.

common terms used • involved field• extended field• total lymphoid irradiation (TLI)• Whole-Abdomen Treatment : mesenteric lymph nodes –

involved

RT Planning & DoseDefinition of • the treatment volume

– Stomach – +/- Duodenum or GO Junction – + Perigasrtic & Regional Lymphnode

• critical organs and dose-limiting structures.

The doses used to treat NHL are usually lower than those required to control solid tumors, allowing irradiation of larger volumes of tissue with a lower risk of serious complications.

RT Doses of 30 to 45 Gy

– Large Volumes: 125-150cGy/Fraction, 5Fx/week– Small volume : 180 cGy/Fx, 5Fx/week

interfractional gastric movement during radiation therapy.

Tumor position and location - clips endoscopically placed

directions : Target Motion range

lateral : 5 and 35 mm (mean 24 mm) cephalocaudal:0-15 mm (8 mm).

RT Machines• Telecobalt

• Linear Accelerator

Recent Advances

• 3 DCRT – 3D Conformal

• IMRT - Intensity Modulated

• IGRT

• Tomotherapy

• Cyber Knife

Tomotherapy

linacMLC

CyberKnife

Simulation X- Ray

Radiation treatment planning techniques for lymphoma of the stomach.

type I: patients (no overlap between PTV and kidneys)- there was essentially no benefit from using 3DCRT over AP/PA.

type II : PTVs in close proximity to the kidneys) type III: with high degree of overlap – the 4-field 3DCRT plans were superior, reducing the kidney V(15 Gy)

by approximately 90% for type II and 50% for type III patients. – For type III, the use of a 3DCRT plan rather than an AP/PA plan

decreased the V(15 Gy) by approximately 65% for the right kidney and 45% for the left kidney.

– In the selected cases, IMRT led to a further decrease in left kidney dose as well as in mean liver dose.

– The addition of IMRT led to further incremental improvements in the left kidney and liver dose in selected patients.

RESULTS

Gastric Lymphoma Localized treated with radiation therapy

PRE RT

End of RTF/U – at 1 yr

MALT (MSKCC)

• n = 51 (h.pylori –ve / persistant after antibiotic therapy)

• Stage I – 39, II – 10, IV – 2

• RT : stomach + perigastric lymph nodes

: 30Gy in 4 weeks

• CR – 96% (49/51)

• 4yrs f/u : • freedom from treatment failure – 89%, • OS – 83%• cause specific survival – 100%.

Adjuvant therapy:

• Resectability rate : 60-80%– Curative resection – 50-87% (5yrs survival)– Non –resectable – 6-40%

• Stage IE : RT alone = S + RT ~ 85% (burgers et al)

RT & CT

• Maro et al

• n =34 (Stage IE & II E )

• 5 – 15 yrs OS - 68%

• Koch, P. et al S• n =747.• 393 with localized PGL• Treated with radiotherapy and/or chemotherapy only

or additional surgery • The survival rate at 42 months for patients treated with

surgery was 86% compared with 91.0% for patients without surgery.

acute radiation side effects

• mild nausea (RTOG Grade 1) -100%

• appetite loss -Grade 1 < 5%.

• no severe late adverse events.

• left kidney atrophy of approximately 10%, but no renal dysfunction < 1%.

Radiotherapy Results & Conclusion

survival rates

• stage IE and IIE : 80%-89% .

• early stages of MALT lymphomas not responding to antibiotics: 93%

• post-operative RT (in high- and low-grade lymphomas) for any residual tumors in stages I and II : improve the disease free survival. Stage IE : RT alone = S + RT ~ 85% (burgers et al)

• Combined chemotherapy - improves the

chance of stomach conservation ~100%.

• combined radiotherapy with either

resection or chemotherapy is not

significantly difference in both modalities

with a survival rate of 82%-88%.

• No risk of bleeding or perforation

• Equivalent outcome can be attained

without gastric resection

Primary gastrointestinal lymphoma--disease spectrum and management : a 15-year review from north India.

Singh DP et al, Postgraduate Institute of Medical Education and Research, Chandigarh.,

• Seventy five • 1971 -1985 • Age: 3.5-69 years (mean 34) at presentation• Histologically,

– diffuse poorly-differentiated lymphocytic lymphoma (46.7%) and diffuse histiocytic type (30.7%).

• stage I - 27(36%) • stage II - 31 (40%) • stage III - 11 (14.7%) • stage IV - 6 (8%).

– Surgery:• primary resection - 66 • biopsies -9

– Treatment {mean follow-up was 3.9 years (range 1-14)}. • adjuvant radiation with or without chemotherapy - 48 • The 5-year actuarial survival was• stages I - 34%, II- 25% and higher-stage- 16% • The survival was significantly better (p < 0.01) for gastric location (44%) compared to

other sites (24%).