Retrospective Studies Of Limited Treatment

In a recent review, Conners wrote, "... there is no definite evidence that LPHL is less curable than CHL . . ."49 In another review, Diehl concluded, "there is no rationale for a less intensive treatment" of LPHL compared with CHL.39 Yet he suggested that these "treatment strategies might be too intensive, particularly when late effects such as secondary malignancies and cardiac and pulmonary complications are taken into account." Several authors have suggested that the management of these patients should try to minimize therapy-related complications.30'383949 On the other hand, Diehl noted that the subsequent development of disease-related, rather than treatment-related, NHL in some patients suggests the need to retain (rather than reduce) currently effective primary therapy.39 In fact, retrospective analyses support less intensive treatment at least for some patients.

Several groups have reviewed the outcome of LPHL patients treated with limited RT. In 1995, the Harvard Collaborative Oncology Group published the preliminary results of a combined prospective and retrospective analysis of 46 patients with PS I-IIA HL treated with mantle field RT alone between 1970 and 1993.50 The prospective study was limited to patients with nodular sclerosis or LPHL and no risk factors (i.e., B symptoms, mediastinal mass greater than 1/3 of the thoracic diameter on a standing posteroanterior chest radiograph, and no subcarinal or hilar adenopathy). With a median follow-up of 32 (range 13-58) and 113 (range 56-296) months in the prospectively and retrospectively studied patients, respectively, none of the 16 LPHL patients had relapsed. The prospective study was recently updated.51 Between October 1988 and June 2000, 87 patients with PS IA-IIA HL received 30.6-44 Gy mantle field RT. After 1995, patients with PS IA mixed cellularity, CS IA LPHL, and females with CS IA nodular sclerosis HL were also enrolled. Of the 77 pathologically staged patients, 37 had PS IA and 40 had PS IIA disease. Six patients had CS IA disease. With a median follow-up of 61 (range 13-127) months, none of the 15 LPHL patients had relapsed. Wirth et al. retrospectively studied 261 Australian patients with CS I-II HL treated with 30-40 Gy mantle field RT alone between 1969 and 1994.52 With a median follow-up for surviving patients of 8.4 (range 1.8-27.4) years, the

10-year overall survival was 73%. On mulitvariable analysis for overall survival, age was the only important prognostic factor. The 10-year progression-free survival was 58%. On multivariable analysis, the progression-free survival was significantly better for patients with LP histology, nonmediastinal bulk less than 10 cm, three or fewer involved sites, no B symptoms, stage I, and performance status 0. The 10-year progression-free survival for 56 LPHL patients was 81% for stage I and 78% for stage II with no relapse or deaths beyond 10 years.

Patients with supradiaphragmatic CS IA LPHL have a very low probability of having disease detected below the diaphragm at staging laparotomy.5354 And, as noted earlier, mediastinal involvement in NLPHL is very uncommon. These data suggest that patients with CS IA NLPHL might be candidates for very limited RT. Surprisingly, little data are available on the outcome of patients with LPHL (or NLPHL as defined by the REAL/WHO criteria), who were clinically staged with modern imaging studies and treated with limited RT. Early studies showed that IFRT alone was not adequate for unselected patients with early stage HL.55 56 Several studies, however, recognized the excellent outcome of young LPHL patients with PS or CS IA limited to suprahyoid cervical lymph node(s). Relapse following IFRT in this subset of patients is rare.1457-59 Recently, Schlembach et al. reported the outcome of 36 NLPHL patients (retrospectively diagnosed according to the REAL/WHO criteria) with nonbulky, stage IA (n = 27) or IIA (n = 9) involving three or less nodal regions above (n = 27) or below the diaphragm (n = 9), who received a median of 40-Gy RT alone at the MD Anderson Cancer Center between 1963 and 1996.60 The majority of patients received "limited-field," i.e., IF (n = 3), regional (n = 18), mantle or inverted Y +/— spleen (n = 7); the rest of the patients received EF, i.e., subtotal or total nodal irradiation (n = 8). For the 24 patients with PS IA (n = 8) or CS IA (n = 16) NLPHL who received IF or regional radiotherapy, the 5-year relapse-free and overall survival were 96% and 100%, respectively. The GHSG recently presented the preliminary findings from a study in which 89 patients with CS IA NLPHL and no risk factors were treated with IFRT (n = 44), two to four cycles of ABVD followed by 20-30 Gy IFRT (n = 25), ABVD chemotherapy alone (n = 2), or an unknown therapy (n = 1).61 Ninety-seven percent of the patients achieved a complete or unconfirmed complete remission. Two patients have relapsed and no patients have died. Follow-up, however, is relatively short.

Because of the excellent overall survival (regardless of the specific treatment) and the risk associated with treatment as well as the observations from a few reports, some authors have considered a "watch and wait" approach.13 2962 In one study, 31 minimally staged patients, who were initially considered to have benign lymphadenopathy but were subsequently diagnosed with LPHL, received no treatment following excision of the involved lymph node(s).12 With median follow-up of 7 years, seven patients died 1-11 years after surgery— only one from HL and three from NHL, two from carcinoma, and two from other causes. In another study of 145 cases of LPHL, 24 stage I patients received no therapy following excision of the involved lymph node(s).13 Fifteen of these 24 patients relapsed but 9 remained free of disease for 7-14 years. In 1988, the French Society of Pediatric Oncology (FSOP) initiated a prospective, nonrandomized study.38 At the physician's discretion, 27 children with NLPHL were either observed following lymph node excision (n = 13) or received (according to FSOP protocols) chemotherapy with or without 20-Gy RT. Nine of 13 observed patients had no evidence of disease following lymphadenectomy. Seven of 13 observed patients progressed a median of 24 (range 4-120) months after surgery. With a median follow-up of 70 months, 12 of 13 patients are in first (n = 7), second (n = 3), third (n = 1), or fifth (n = 1) remission and all of the patients are alive.

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