- Email: [email protected]
Mass screening for neuroblastoma at 6 months of age – Authors' reply
Correspondence
Prescreening cohort (n=6 130 423)
Qualitative screening cohort
Quantitative screening cohort
Screened children (n=4 092 759)
Unscreened children (n=1 197 653)
Screened children (n=9 342 132)
Unscreened children (n=1 526 728)
423
19
1421
39
Neuroblastoma cases
66
Deaths
12 (18·2%)
15 (3·55%)
5 (26·3%)
23 (1·62%)
10 (25·6%)
8 (12·1%)
4 (0·95%)
3 (15·8%)
11 (0·77%)
4 (10·3%)
<3 years after diagnosis
2 (3·03%)
2 (0·47%)*
1 (5·26%)
6 (0·42%)†
≥3 years after diagnosis
0
2 (0·47%)‡
0
0
1 (2·56%)
Late tumour-related death
0
3 (0·71%)
0
0
1 (2·56%)
Other cause
1 (1·52%)
4 (0·95%)
0
3 (0·21%)
0
Unknown
1 (1·52%)
0
1 (5·26%)
3 (0·21%)
2 (5·13%)
Cause of death Progressive disease Treatment-related death 2 (5·13%)
*One operational death and one death from renal failure. †Three toxicity-related deaths (cardiopathy, encephalopathy, and pneumonia), two infections, and one surgical complication). ‡Two cases of therapy-related myeloproliferative disorder.
Table: Causes of death in neuroblastoma patients diagnosed at between 6 and 11 months of age
Some neuroblastomas diagnosed by mass screening regress spontaneously.2 These findings suggest that patients with low-risk neuroblastoma diagnosed by mass screening might have received overtreatment, which could cause unexpected morbidity and mortality. We would be grateful if Hiyama and colleagues could provide us with information on secondary cancers and long-term adverse reactions of the survivors in this cohort study. We declare that we have no conflict of interest.
*Yuji Miura, Masahiro Kami, Masaharu Tsubokura, Naoko Takei, Tsunehiko Komatsu [email protected] Teikyo University, Chiba Medical Center, Ichihara, Chiba 299-0111, Japan 1
2
Hiyama E, Iehara T, Sugimoto T, et al. Effectiveness of screening for neuroblastoma at 6 months of age: a retrospective population-based cohort study. Lancet 2008; 371: 1173–80. Oue T, Inoue M, Yoneda A, et al. Profile of neuroblastoma detected by mass screening, resected after observation without treatment: results of the Wait and See pilot study. J Pediatr Surg 2005; 40: 359–63.
Authors’ reply As Yuji Miura and colleagues mention, early treatment at 6–11 months of age decreased the mortality rate in the quantitative screening group, but intensive therapy, although necessary for stage 4 tumours, is a risk factor www.thelancet.com Vol 372 August 2, 2008
for secondary cancers and long-term adverse reactions. We have already calculated the causes of death in patients whose neuroblastoma was diagnosed at between 6 and 11 months of age (table). Late treatment-related deaths—two cases of myeloproliferative disorders—were seen only in the qualitatively screened children. During the early period after the launch of screening, many screeningdetected cases were treated with chemotherapy and radiotherapy in addition to surgery. Thus, these myeloproliferative disorders in qualitatively screened children were probably induced by the intensive therapy. At the beginning of 1990, infants with localised neuroblastoma were shown to have an excellent prognosis with low-dose chemotherapy in several studies.1,2 Also, in the neuroblastoma patients detected by the Japanese mass screening programme, the prognosis was excellent except for MYCN-amplified tumours.3 Then we started the Japanese Infantile Neuroblastoma Cooperative Study on fewer therapy-related complications for infant neuroblastoma in 1994. In this study, low-risk tumours undergo only surgery. Thus, in quantitatively screened children, there have been no secondary cancers.
Although some tumours detected by screening regress spontaneously,4 our study indicated that tumours detected by screening that would progress later were detected earlier and cured by surgery only.5 The reduction in the risk of secondary cancers and long-term adverse reactions is an immeasurable benefit. We declare that we have no conflict of interest.
*Eiso Hiyama, Tomoko Iehara [email protected] Natural Science Centre for Basic Research and Development, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan 1
2
3
4
5
De Bernardi B, Conte M, Mancini A, et al. Localized resectable neuroblastoma: results of the second study of the Italian Cooperative Group for Neuroblastoma. J Clin Oncol 1995; 13: 884–93. Rubie H, Coze C, Plantaz D, et al. Localised and unresectable neuroblastoma in infants: excellent outcome with low-dose primary chemotherapy. Br J Cancer 2003; 89: 1605–09. Iehara T, Hosoi H, Akazawa K, et al. MYCN gene amplification is a powerful prognostic factor even in infantile neuroblastoma detected by mass screening. Br J Cancer 2006; 94: 1510–15. Oue T, Inoue M, Yoneda A, et al. Profile of neuroblastoma detected by mass screening, resected after observation without treatment: results of the Wait and See pilot study. J Pediatr Surg 2005; 40: 359–63. Hiyama E, Iehara T, Sugimoto T, et al. Effectiveness of screening for neuroblastoma at 6 months of age: a retrospective population-based cohort study. Lancet 2008; 371: 1173–80.
373
Prescreening cohort (n=6 130 423)
Qualitative screening cohort
Quantitative screening cohort
Screened children (n=4 092 759)
Unscreened children (n=1 197 653)
Screened children (n=9 342 132)
Unscreened children (n=1 526 728)
423
19
1421
39
Neuroblastoma cases
66
Deaths
12 (18·2%)
15 (3·55%)
5 (26·3%)
23 (1·62%)
10 (25·6%)
8 (12·1%)
4 (0·95%)
3 (15·8%)
11 (0·77%)
4 (10·3%)
<3 years after diagnosis
2 (3·03%)
2 (0·47%)*
1 (5·26%)
6 (0·42%)†
≥3 years after diagnosis
0
2 (0·47%)‡
0
0
1 (2·56%)
Late tumour-related death
0
3 (0·71%)
0
0
1 (2·56%)
Other cause
1 (1·52%)
4 (0·95%)
0
3 (0·21%)
0
Unknown
1 (1·52%)
0
1 (5·26%)
3 (0·21%)
2 (5·13%)
Cause of death Progressive disease Treatment-related death 2 (5·13%)
*One operational death and one death from renal failure. †Three toxicity-related deaths (cardiopathy, encephalopathy, and pneumonia), two infections, and one surgical complication). ‡Two cases of therapy-related myeloproliferative disorder.
Table: Causes of death in neuroblastoma patients diagnosed at between 6 and 11 months of age
Some neuroblastomas diagnosed by mass screening regress spontaneously.2 These findings suggest that patients with low-risk neuroblastoma diagnosed by mass screening might have received overtreatment, which could cause unexpected morbidity and mortality. We would be grateful if Hiyama and colleagues could provide us with information on secondary cancers and long-term adverse reactions of the survivors in this cohort study. We declare that we have no conflict of interest.
*Yuji Miura, Masahiro Kami, Masaharu Tsubokura, Naoko Takei, Tsunehiko Komatsu [email protected] Teikyo University, Chiba Medical Center, Ichihara, Chiba 299-0111, Japan 1
2
Hiyama E, Iehara T, Sugimoto T, et al. Effectiveness of screening for neuroblastoma at 6 months of age: a retrospective population-based cohort study. Lancet 2008; 371: 1173–80. Oue T, Inoue M, Yoneda A, et al. Profile of neuroblastoma detected by mass screening, resected after observation without treatment: results of the Wait and See pilot study. J Pediatr Surg 2005; 40: 359–63.
Authors’ reply As Yuji Miura and colleagues mention, early treatment at 6–11 months of age decreased the mortality rate in the quantitative screening group, but intensive therapy, although necessary for stage 4 tumours, is a risk factor www.thelancet.com Vol 372 August 2, 2008
for secondary cancers and long-term adverse reactions. We have already calculated the causes of death in patients whose neuroblastoma was diagnosed at between 6 and 11 months of age (table). Late treatment-related deaths—two cases of myeloproliferative disorders—were seen only in the qualitatively screened children. During the early period after the launch of screening, many screeningdetected cases were treated with chemotherapy and radiotherapy in addition to surgery. Thus, these myeloproliferative disorders in qualitatively screened children were probably induced by the intensive therapy. At the beginning of 1990, infants with localised neuroblastoma were shown to have an excellent prognosis with low-dose chemotherapy in several studies.1,2 Also, in the neuroblastoma patients detected by the Japanese mass screening programme, the prognosis was excellent except for MYCN-amplified tumours.3 Then we started the Japanese Infantile Neuroblastoma Cooperative Study on fewer therapy-related complications for infant neuroblastoma in 1994. In this study, low-risk tumours undergo only surgery. Thus, in quantitatively screened children, there have been no secondary cancers.
Although some tumours detected by screening regress spontaneously,4 our study indicated that tumours detected by screening that would progress later were detected earlier and cured by surgery only.5 The reduction in the risk of secondary cancers and long-term adverse reactions is an immeasurable benefit. We declare that we have no conflict of interest.
*Eiso Hiyama, Tomoko Iehara [email protected] Natural Science Centre for Basic Research and Development, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan 1
2
3
4
5
De Bernardi B, Conte M, Mancini A, et al. Localized resectable neuroblastoma: results of the second study of the Italian Cooperative Group for Neuroblastoma. J Clin Oncol 1995; 13: 884–93. Rubie H, Coze C, Plantaz D, et al. Localised and unresectable neuroblastoma in infants: excellent outcome with low-dose primary chemotherapy. Br J Cancer 2003; 89: 1605–09. Iehara T, Hosoi H, Akazawa K, et al. MYCN gene amplification is a powerful prognostic factor even in infantile neuroblastoma detected by mass screening. Br J Cancer 2006; 94: 1510–15. Oue T, Inoue M, Yoneda A, et al. Profile of neuroblastoma detected by mass screening, resected after observation without treatment: results of the Wait and See pilot study. J Pediatr Surg 2005; 40: 359–63. Hiyama E, Iehara T, Sugimoto T, et al. Effectiveness of screening for neuroblastoma at 6 months of age: a retrospective population-based cohort study. Lancet 2008; 371: 1173–80.
373