Histologic survey of neuroblastomas after intensive induction chemotherapy

Abstract

Histology after intensive induction chemotherapy is expected to become a beacon indicating when and how extensively radical surgery and lymph node dissection should be performed in advanced neuroblastoma. A thorough histologic review of surgical specimens was undertaken. All specimens from 34 patients who were pretreated intensively (> or =3 cycles) with recent chemotherapy were reviewed. Thirty patients were >12 months of age with stage 3/4 disease, and 4 were <12 months of age but with MYCN-amplified stage 4 diseases. After 3 to 7 cycles (mean, 4.3 cycles) of induction chemotherapy, patients underwent radical surgery of the primary tumor and lymph nodes in all retroperitoneal sections. A single pathologist reviewed all of the specimens, and histologic chemotherapeutic effects were graded as: (+++), <1% viable tumor; (++), 1%-10% viable tumor; (+), 11%-50% viable tumor; (+/-), 51%-90% viable tumor; and (-), >91% viable tumor. Grade (+++) effects were observed in 56% of patients treated with the new regimens, whereas grade (+++) was seen in only 20% treated with regimens before 1991. Operation time and blood loss were 7 hr and 6 min (P = 0.087) and 646 ml (P = 0.064), respectively, in patients with >5 cycles (mean, 5.3 cycles) of chemotherapy, while they were 7 hr and 50 min and 1,168 ml, respectively, in those with approximately 3 cycles (mean, 3.2 cycles). Histologically, metastases were found in the contralateral nodes beyond the aorta in 92% of those whose tumor originated on the left, and in 80% of those with tumors occurring on the right. Five cycles of induction chemotherapy did not improve histologic chemotherapeutic effects, but helped to facilitate a shorter operation time and less blood loss than 3 cycles of chemotherapy. Surgery after 5 cycles of (98)A(3) also appears to be easier to perform than that after 3 cycles of A(1)/new A(1). Only 14% of the children treated before 1985 with the St. Jude protocols experienced grade (+++) chemotherapeutic effects, and 22% of the patients treated before 1991 with regimen A(1), or new A(1) of the Study Group of Japan showed grade (+++) effects, whereas 56% of the patients treated after 1991 with either regimen A(3) or (98)A(3) exhibited grade (+++) chemotherapeutic effects. Histologic chemotherapeutic effects were roughly parallel with a good prognosis.