# Radiation Oncology/NHL/Specific sites

* Front Page: Radiation Oncology | RTOG Trials | Randomized Trials
* Non-Hodgkin lymphoma: Main Page | Randomized
* Overview: Overview |
* Follicular |
* Diffuse large B-cell |
* MALT |
* Nodal marginal zone |
* Mantle cell |
* CLL/SLL |
* Lymphoblastic |
* Burkitt |
* NK/T cell |
* Anaplastic large cell |
* Primary CNS Lymphoma
* Treatment:
* Aggressive |
* Specific sites |
* Radioimmunotherapy

## Primary CNS Lymphoma

* Please see Primary CNS Lymphoma for detailed information

## Orbit

Eye and Orbital Lymphoma
* U.Florida; 1999 (1969-1995)
** PMID 10219791 -- "Radiotherapy in the management of orbital lymphoma." (Bolek TW, Int J Radiat Oncol Biol Phys. 1999 Apr 1;44(1):31-6.)
*** 38 pts; 20 pts treated with curative intent, 18 with palliation. No chemotherapy. RT with cobalt or kilovoltage x-ray. Median dose 25 Gy (median dose/fraction 1.67 Gy)
*** LC in 37 of 38 pts. Curative treatment: 5-yr CSS 89% (low grade) and 33% (int/high grade).
*** Cataract formation in 7 of 21 pts treated without lens shielding; 0 of 17 pts with lens shielding.
*** Conclusion: "Radiotherapy is a safe and effective local treatment in the management of orbital lymphoma."
* MGH; 1990 (1979-1988)
** PMID 2118492 -- "Conjunctival lymphoma: results and treatment with a single anterior electron field. A lens sparing approach." (Dunbar SF, Int J Radiat Oncol Biol Phys. 1990 Aug;19(2):249-57.)
*** 12 pts. Treated with 6-9 MeV electron beam, dose 24-30 Gy (median 30 Gy; median 250 cGy x 12 fractions)
*** LC in all pts at f/u of 0.5-9.5 yrs.

## Skin

* Please see Mycosis fungoides for T-cell lymphoma or Cutaneous B-cell lymphoma

## Head & Neck
### Thyroid

    See page at Thyroid lymphoma

### Waldeyer's Ring

    See anatomic description at Radiation_Oncology/Hodgkin/Overview#Anatomy; traditional RT fields at Radiation_Oncology/Hodgkin/Overview#Radiation fields
Waldeyer's ring includes the tonsil, nasopharynx, and base of tongue.
* Mexico (1981-91) — 1996 - Treatment of non-Hodgkin's lymphoma of Waldeyer's ring: radiotherapy versus chemotherapy versus combined therapy. (Aviles A, Eur J Cancer B Oral Oncol. 1996 Jan;32B(1):19-23.)
** 316 pts. Phase III. Stage I NHL of Waldeyer's ring. Randomized to extended-field RT alone, chemotherapy alone (CHOP or CHOP-like), or combined therapy with chemo + RT.
** Median f/u 6.8 yrs. CR in 93%, 87%, 97%. 5-yr FFS 48%, 45%, 83% (SS); OS 56%, 58%, 90% (SS).
** Conclusion: improved results with combined chemo+RT.

## GI tract

GI lymphomas account for 4-12% of all NHL and 1-4% of GI tumors. 20-40% involve the small bowel. There is a subtype called enteropathy-type intestinal T-cell lymphoma.

### Stomach

* Italy; 2009 (1998-2004) PMID 19479614 -- "Early stage gastric diffuse large B-cell lymphomas: results of a randomised trial comparing chemotherapy alone versus chemotherapy + involved field radiotherapy." (Martinelli G, Leuk Lymphoma. 2009 May 19:1-7.)
** Randomized. 54 patients, DLBCL gastric lymphoma. Antracycline-containing chemo x4-6 cycles. Those in CR (83%) randomized to Arm 1) IFRT vs Arm 2) 2 additional cycles of chemo
** Outcome: LR RT significantly better. OS no difference
** Conclusion: IFRT able to prevent local relapse
* MSKCC, 2005 - PMID 15936555 — "Radiation treatment planning techniques for lymphoma of the stomach." Della Biancia C et al. Int J Radiat Oncol Biol Phys. 2005 Jul 1;62(3):745-51.
** Comparison of AP/PA vs 3D-CRT vs IMRT for different relationships of the target volume and kidneys.

## Primary Mediastinal Large B-Cell Lymphoma (PMBCL)

* Please see DLBCL/PMLBCL section for background information
Chemotherapy regimens: DA-EPOCH-R, MACOP-B, VACOP-B, NHL-15, R-CHOP
Treatments:
* Dunleavy, 2012 (NCI) PMID 23574119 -- "Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma." (N Engl J Med. 2013 Apr 11;368(15):1408-16)
** Phase 2 prospective prospective study of infusional dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab (DA-EPOCH-R) and filgrastim without radiotherapy in 51 patients with untreated primary mediastinal B-cell lymphoma.
** Outcome: The patients had a median age of 30 years (range, 19 to 52) and a median tumor diameter of 11 cm; 59% were women. During a median of 5 years of follow-up, the event-free survival rate was 93%, and the overall survival rate was 97%. Among the 16 patients who were involved in the retrospective analysis at another center, over a median of 3 years of follow-up, the event-free survival rate was 100%, and no patients received radiotherapy. No late morbidity or cardiac toxic effects were found in any patients. After follow-up ranging from 10 months to 14 years, all but 2 of the 51 patients (4%) who received DA-EPOCH-R alone were in complete remission. The 2 remaining patients received radiotherapy and were disease-free at follow-up.
** Conclusion: Therapy with DA-EPOCH-R obviated the need for radiotherapy in patients with primary mediastinal B-cell lymphoma.
* Padova, 2007 (Italy) PMID 17379431 -- "Primary mediastinal large B-cell lymphoma: results of intensive chemotherapy regimens (MACOP-B/VACOP-B) plus involved field radiotherapy on 53 patients. A single institution experience." (Mazzarotto R, Int J Radiat Oncol Biol Phys. 2007 Jul 1;68(3):823-9.)
** Retrospective. 53 consecutive patients with PMLBCL (90% Stage I-II) treated with induction ProMACE-MOPP (n=2), MACOP-B (n=11), and VACOP-B (n=40), followed by IFRT. RT started 3-4 after chemo, modified mantle and SCV if involved at diagnosis. Dose 30.6/17 - 39.6/22 (mean 36/20). Treatment completed in 80%. Median F/U 7.8 years
** Outcome: 5-year OS 93%, DFS 87%. Response after chemo: CR 38%, PR 57%. If PR, 92% obtained CR after IFRT
** Conclusion: Intensive chemo + IFRT efficacious; IFRT plays a pivotal role in inducing CR
* Verona, 2004 (Italy)(1982-1999) PMID 14735179 -- "Primary mediastinal large B-cell lymphoma (PMLBCL): long-term results from a retrospective multicentre Italian experience in 138 patients treated with CHOP or MACOP-B/VACOP-B." (Todeschini G, Br J Cancer. 2004 Jan 26;90(2):372-6.)
** Retrospective. 13 Italian centers. 138 patients with PMLBCL treated with CHOP (n=43) or MACOP-B/VACOP-B (n=95). 76% patients in CR received IFRT
** Outcome: CR CHOP 51% vs. MACOP-B/VACOP-B 80% (SS); EFS 40% vs. 76% (SS). IFRT improved outcome, irrespective of chemo
** Conclusion: MACOP-B/VACOP-B better than CHOP; consolidation IFRT improves outcome in CR patients
Clinicopathologic Studies:
* Nebraska - PMID 10071267, 1999 -- "Primary mediastinal large B-cell lymphoma: a clinicopathologic study of 43 patients from the Nebraska Lymphoma Study Group." (Abou-Elella AA, J Clin Oncol. 1999 Mar;17(3):784-90.)
** Conclusion: The clinical features of PMLBL do not appear to be significantly different from those of nonmediastinal DLBL. Younger median age of 42 yrs is much less than median age for nonmediastinal DLBL.
Reviews:
* Savage, 2006 - PMID 16720849, 2006 — "Primary mediastinal large B-cell lymphoma." Savage KJ. Oncologist. 2006 May;11(5):488-95.

## Testicular

* International Extranodal Lymphoma Study Group 10 [IELSG-10] - Phase II - R-CHOP, IT-MTX, RT to contralateral testis
** Multinational. 53 pts, Stage I-II primary testicular lymphoma. R-CHOP21 x 6-8, 4 doses of intrathecal MTX, RT 30 Gy to the contralateral testis (for all pts). RT 30-36 Gy given to the pelvis for Stage II.
** 2011 PMID: 21646602-- "First-Line Treatment for Primary Testicular Diffuse Large B-Cell Lymphoma With Rituximab-CHOP, CNS Prophylaxis, and Contralateral Testis Irradiation: Final Results of an International Phase II Trial." (Vitolo U, JCO online before print June 6, 2011.)
*** Median f/u 65 mo. All pts received R-CHOP, 50 received CNS prophylaxis, 47 received testicular RT. 5-yr PFS 74% and OS 85%. 10 pts with relapses: 2 in LNs, 5 in extranodal organs, 3 in CNS. 5-yr CNS relapse rate 6%. No contralateral testis relapses. 10 pts died (6 from lymphoma).
*** Conclusion: Good outcome for PTL with chemotherapy with CNS prophylaxis and RT to the contralateral testis. CNS prophylaxis deserves further investigation.

## Primary Bone Lymphoma

* MD Anderson, 2015 (1988-2013) PMID 25754633 -- "Benefit of consolidative radiation therapy for primary bone diffuse large B-cell lymphoma." (Tao R, Int J Radiat Oncol Biol Phys. 2015 May 1;92(1):122-9. doi: 10.1016/j.ijrobp.2015.01.014. Epub 2015 Mar 5.)
** Retrospective. 102 patient, primary DLBCL. Median age 55. R-CHOP in 63%; Rituximab in 72%. RT in 66% (n=67). Stage I-II in 70%. Median dose 44 Gy (24 - 50). Median F/U 6.8 years
** Outcome: 5-year PFS 80%; OS 82%. RT improved PFS (RT 88% vs no RT 63%, SS) and improved OS (91% vs 68%, SS). No difference between dose <36 Gy vs >= 36 Gy
** Conclusion: Patient treated with chemotherapy and RT can have excellent outcomes
* Rare Cancer Network; 2012 (1987-2008) PMID 22079728 -- "Early-Stage Primary Bone Lymphoma: A Retrospective, Multicenter Rare Cancer Network (RCN) Study." (Cai L, Int J Radiat Oncol Biol Phys. 2012 May 1;83(1):284-91.) -- Median f/u 41 m.
** Multi-institutional. 116 pts, Stages I-II (I-80%, II-20%). Pathology was re-classified using the WHO classification (DLBCL in 78%).
** 75% received chemoradiotherapy. 88% received chemo (+/- RT). Chemo was CHOP in 68%, R-CHOP in 32%.
** CR in 74%. LF in 10%. LC: 5-yr 92%, 10-yr 80%. OS: 5-yr 76%, 10-yr 72%. LSS (lymphoma-specific survival): 78% at 5 and 10 yrs.
** Distant progression in 15% at a median of 7 months.
** By RT dose: LF 12% (for <40 Gy) vs 8% (>40 Gy); NS. LF was in-field in 50%.
** Independent prognostic features: IPI score, RT dose, CR, and chemo.
** Conclusion: Good prognosis. Chemotherapy followed by RT is superior to rt->chemo. RT plays a role in local control. Better outcome for more than 6 chemotherapy cycles and more than 40 Gy RT.
* Italy; 2004 (1983-2001) PMID 15183479 -- "Primary non-Hodgkin's lymphoma of the bone: treatment and analysis of prognostic factors for Stage I and Stage II." (Barbieri E, Int J Radiat Oncol Biol Phys. 2004 Jul 1;59(3):760-4.) -- Median f/u 149 m (12 yr)
** 77 pts with Stage I (44) or Stage II (33) primary bone lymphoma. All pts had RT to median 40 Gy; 67 pts had chemo.
** CR in 94.8%. Relapse in 18.2% at median of 23 months. 15-yr DFS 76.6%, OS 88.3%.
** Prognostic factors: Age <40 was the only significant factor for worse DFS.
** Conclusion: "In PLB the CMT seems to produce a better outcome than RT alone; that still remains the best treatment for local disease control. Radiation therapy alone should be reserved for mandibular tumors, which are usually very small and earlier diagnosed."

## References

* ^ - PMID 10673521. Gale J et al. Enteropathy-type intestinal T-cell lymphoma: clinical features and treatment of 31 patients in a single center.