title: 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.
abstract: OBJECTIVE
  Primary testicular lymphoma (PTL) has poor prognosis with failures in contralateral testis, CNS, and extranodal sites. To prevent these events, we designed an international phase II trial (International Extranodal Lymphoma Study Group 10 [IELSG-10]) that addressed feasibility and activity of conventional chemoimmunotherapy associated with CNS prophylaxis and contralateral testis irradiation. The trial was conducted by the IELSG and the Italian Lymphoma Foundation.
  
  
  METHODS
  Fifty-three patients (age 22 to 79 years) with untreated stage I or II PTL were treated with six to eight courses of rituximab added to cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) every 21 days (R-CHOP21); four doses of intrathecal methotrexate (IT-MTX) and radiotherapy (RT) to the contralateral testis (30 Gy) for all patients and to regional lymph nodes (30 to 36 Gy) for stage II disease.
  
  
  RESULTS
  All patients received R-CHOP21, 50 received CNS prophylaxis, and 47 received testicular RT. With a median follow-up of 65 months, 5-year progression-free survival and overall survival rates were 74% (95% CI, 59% to 84%) and 85% (95% CI, 71% to 92%), respectively. Ten patients relapsed or progressed: two in lymph nodes, five in extranodal organs, and three in the CNS. The 5-year cumulative incidence of CNS relapse was 6% (95% CI, 0% to 12%). No contralateral testis relapses occurred. Ten patients died: lymphoma (n = 6), secondary leukemia (n = 2), heart failure (n = 1), and gastric cancer (n = 1). Grade 3 to 4 toxicities were neutropenia, 28%; infections, 4%; and neurologic, 13%. No deaths occurred as a result of toxicity.
  
  
  CONCLUSIONS
  This international prospective trial shows that combined treatment with R-CHOP21, IT-MTX, and testicular RT was associated with a good outcome in patients with PTL. RT avoided contralateral testis relapses, but CNS prophylaxis deserves further investigation.
authors.affiliation: Battista Hospital and University, Turin, Italy. uvitolo@molinette.piemonte.it
authors.forename: Umberto
authors.initials: U
authors.lastname: Vitolo
authors.forename: Annalisa
authors.initials: A
authors.lastname: Chiappella
authors.forename: Andrés J M
authors.initials: AJ
authors.lastname: Ferreri
authors.forename: Maurizio
authors.initials: M
authors.lastname: Martelli
authors.forename: Ileana
authors.initials: I
authors.lastname: Baldi
authors.forename: Monica
authors.initials: M
authors.lastname: Balzarotti
authors.forename: Chiara
authors.initials: C
authors.lastname: Bottelli
authors.forename: Annarita
authors.initials: A
authors.lastname: Conconi
authors.forename: Henry
authors.initials: H
authors.lastname: Gomez
authors.forename: Armando
authors.initials: A
authors.lastname: Lopez-Guillermo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.forename: Francesco
authors.initials: F
authors.lastname: Merli
authors.forename: Domenico
authors.initials: D
authors.lastname: Novero
authors.forename: Lorella
authors.initials: L
authors.lastname: Orsucci
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Pavone
authors.forename: Umberto
authors.initials: U
authors.lastname: Ricardi
authors.forename: Sergio
authors.initials: S
authors.lastname: Storti
authors.forename: Mary K
authors.initials: MK
authors.lastname: Gospodarowicz
authors.forename: Franco
authors.initials: F
authors.lastname: Cavalli
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Sarris
authors.forename: Emanuele
authors.initials: E
authors.lastname: Zucca
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000517:prevention & control* / Q000556:secondary; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D011446:Prospective Studies; D012008:Recurrence; D000069283:Rituximab; D016019:Survival Analysis; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D016896:Treatment Outcome; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone; D008727:Methotrexate