Radiation therapy improves treatment outcome in patients with diffuse large B-cell lymphoma Luigi Marcheselli, Raffaella Marcheselli, Alessia Bari, Eliana Valentina Liardo, Fortunato Morabito, Luca Baldini, Maura Brugiatelli, Francesco Merli, Nicola Di

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Radiation therapy improves treatment outcome in
patients with diffuse large B-cell
lymphomaLuigi Marcheselli, Raffaella
Marcheselli, Alessia Bari, Eliana Valentina
Liardo, Fortunato Morabito, Luca Baldini, Maura
Brugiatelli, Francesco Merli, Nicola Di Renzo,
and Stefano Sacchi
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• Diffuse large B-cell lymphoma (DLBCL) is the most
  frequently occurring subtype of non-Hodgkins
  lymphoma (NHL) and constitutes 30 to 40 of all
  adult NHLs
• For more than 20 years, combination chemotherapy
  with cyclophosphamide, doxorubicin, vincristine,
  and prednisone (CHOP) has been the standard
  treatment for these patients

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NCCN Giudelines Version 3.2011Non-Hodgkins
LymphomasPRINCIPLES OF RADIATION THERAPY

• Field Involved-Field or Reduced IF
• For Extranodal sites Organ involvement,
  Bone/Spine Involvement
• For Nodal sites IF, RT consolidation after CHT
  limited to the originally involved nodes
• Dose consolidation in DLBCL following CR to CHT
  30-36 Gy for PR after CHT 40-50 Gy

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• The issue of whether the administration of RT
  after chemotherapy (CHT) is beneficial to
  patients with DLBCL remains unresolved.
  Therefore, the aim of this study was to determine
  whether RT was of benefit in our set of patients.

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PATIENTS AND METHODS (1)

• Cases were retrieved from the Gruppo Italiano
  Studio Linfomi (GISL) archive. Patients were
  included in this study if they fulfilled the
  following criteria
• histologically confirmed diagnosis of DLBCL CD
  20, previously untreated
• age gt18 years
• no primary central nervous system involvement
• no human immunodeficiency virus, hepatitis B
  virus, or hepatitis C virus infection
• no severe coincident illnesses
• availability of data on clinical and laboratory
  characteristics, treatments, outcome, and
  follow-up
• Patients included in this retrospective study
  were enrolled in two GISL clinical trials
  (Anzinter3, and LA05)

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PATIENTS AND METHODS (2)

• All patients were treated with R-CHOP with or
  without IFRT at GISL sites.
• All patients included in these trials completed
  six cycles of CHT.
• At completion of CHT, consolidative or adjuvant
  IFRT was allowed, at the treating physicians
  discretion, in patients who had obtained complete
  (CR) or partial (PR) remission, because the trial
  protocols did not specify how RT was to be used.
• It is assumed that IFRT was more likely to be
  given to patients with previously bulky disease,
  diseases with extranodal involvement, and
  diseases that failed to achieve CR upon CHT.

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RESULTS

• 216 patients with a median follow-up of 30 months
  were enrolled in the two GISL protocols between
  2003 and 2007
• 34 patients (16) received ? 6 cycles of R-CHOP
  or obtained less than a PR and were excluded from
  the study
• The remaining 182 patients, of which 153 (84)
  obtained CR and 29 (16) PR, were the target
  cohort of our study

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The clinical characteristics of these 182
patients were as follows median age, 69
years51 male65 stage III-IV5 PS ?1 73 IPI
? 126 bulky disease Comparisons between the
characteristics of patients who received IFRT and
those who did not, showed that younger patients,
patients with bulky disease, and patients with
stage III disease received IFRT more frequently
these differences were statistically significant
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• After chemotherapy, 40 (22) of 182 patients who
  achieved CR or PR were treated with consolidative
  (31 patients) or adjuvant (9 patients) IFRT.
• IFRT was delivered to 21 of 63 (33) patients
  with stage III disease and 19 of 119 (16)
  patients with stage IIIIV disease
• Extra-nodal sites were irradiated in 20 of
  patients
• The median dose delivered was 34 Gy (range 2040
  Gy)
• We do not have information about the criteria
  used by physicians when deciding to use IFRT and
  dose.

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• The comparison between survival outcome of the 40
  patients who obtained CR or PR and who were
  treated with consolidative or adjuvant IFRT with
  the outcome of the 142 non-irradiated patients
  showed a 5-year OS of 86 and 74 respectively
  (p0.118), and an EFS of 85 and 56 respectively
  (p0.021)

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• When the 31 of 153 patients who obtained CR and
  were treated with consolidative IFRT were
  considered, the comparison with the 122
  non-irradiated patients showed a 5-year OS of 91
  and 79, respectively (p0.141), and an EFS of
  88 and 59, respectively (p0.035)

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• Univariate analysis showed that a poorer EFS was
  associated with increasing age, Ann Arbor (AA)
  stage IIIIV, PS gt1, and LDH gt UNL, whereas a
  reduction of risk was associated with IFRT
  treatment.
• We observed the same results for both cohorts
  (182 patients with CR/PR and 153 patients with CR
  after chemotherapy) under examination.
• In multivariate analysis, IFRT had a favorable
  effect for both the 182 patients with CR/PR
  (p0.044) and the 153 patients with CR (p0.037).
  In addition to IFRT, increasing age and stage
  IIIIV remained the principal variables
  associated with EFS. The results of uni- and
  multivariate analyses for EFS are reported in
  Table III

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DISCUSSION (1)

• Whether the administration of RT after
  chemotherapy is of benefit in DLBCL patients has
  not been completely resolved, in part due to
  conflicting results from several trials.
• Recognizing the lack of definitive evidence, the
  National Comprehensive Cancer Network (NCCN)
  guidelines recommend three cycles of R-CHOP plus
  IFRT for early-stage, non-bulky disease, but also
  allow the administration of six to eight cycles
  of R-CHOP with or without IFRT.

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DISCUSSION (2)

• Our retrospective study showed that IFRT
  delivered after six cycles of R-CHOP was
  associated with improved EFS.
• In our group of patients, we collected
  information regarding the site of irradiation and
  dose. Criteria used by physicians to decide
  whether to use IFRT remain unclear because of the
  retrospective nature of the study.
• Finally, we believe that our results strongly
  support the hypothesis that IFRT has a clinically
  useful role, even in the R era.

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CONCLUSION

• In conclusion, the role of RT in the treatment of
  DLBCL, at either early or advanced stages, is
  still unclear.
• The introduction of new treatments and
  technologies must be taken into account to define
  the value of RT.
• Only a program of prospective randomized clinical
  trials can produce a high quality data and
  address questions about which DLBCL patients are
  most likely to benefit from IFRT.

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Stefano Sacchi
Samantha Pozzi Alessia Bari Eliana Liardo
Raffaella Marcheselli Luigi Marcheselli
Monica Civallero Maria Cosenza
.GRAZIE PER LATTENZIONE