Treatment History

Video showing Will chronologically from diagnosis at 7 months of age.




HISTORY
William Lacey is a now 5 year old male with relapsed neuroblastoma. Will initially presented as an infant in 3/05 with a left sided supra-clavicular node, left arm and facial swelling, and left sided Horner’s. CT scan showed multiple cervical lymph nodes, a large posterior mediastinal mass along the spinal column which by MRI had tendrils invading the neural foramina. Bone scan at the time showed no evidence of bony lesions. MIBG showed uptake in the left mediastinum and supraclavicular lesion. In hindsight, there was also a small MIBG avid lesion in the left humerus which was initially not identified, but was re-reviewed and identified at relapse. BMA/BMBx were negative for disease. Urine neuroblastoma markers were mildly elevated. N-myc was non-amplified, DNA Ploidy 1, Shimada favorable, LDH normal (343 U/L), Ferritin elevated (119.7 ng/ml). Thus, at diagnosis Will was classified as a Stage III Intermediate Risk Neuroblastoma, unfavorable biology, although based upon the arm lesion should have been classified as Stage IV Intermediate Risk Neuroblastoma, unfavorable biology.

He was enrolled in COG protocol POG 3961 and received a total of 8 cycles of chemotherapy. While Will had a good initial response to chemotherapy after two cycles with shrinkage of his mediastinal mass, after four cycles his mass was essentially unchanged. The decision was therefore made to proceed with local control via surgery earlier than initially planned because of the possibility that Will’s tumor was maturing rather than shrinking. Will underwent a debulking procedure in 8/05 after six cycles of chemotherapy. As much tumor as possible was resected while maintaining the brachial plexus. Pathology revealed intermixed mature and immature neuroblastoma, and therefore Will received two more courses of chemotherapy. At the end of therapy, CT scan showed a residual posterior mediastinal mass, which remained MIBG avid, a stable arm lesion in the left humerus, and no other sites of disease. He was therefore classified as a VGPR and came off therapy in 10/05.

At his first routine follow-up in 2/06 Will had a routine CT scan which showed interval enlargement in his primary mass as well as a new left internal mammary adenopathy and new left jugular adenopathy, both concerning for recurrence. Urine HVA and VMA were normal. MIBG revealed these lesions to be MIBG avid, and a new abdominal lesion near the splenic flexure which did not have a correlate by CT scan. Given the likelihood of recurrence, Will went to the operating room on 3/20/06 where he had removal of the posterior jugular and internal mammary adenopathy, and a small biopsy of his residual posterior mediastinal mass. Pathology confirmed recurrent neuroblastoma with the same biology in both sets of lymph nodes and the residual mass. BMA/BMBx at this time did not show any evidence of neuroblastoma. Post-operatively a repeat CT scan revealed new pleural based nodules, some of which were able to be seen in a concurrent MIBG. At this point Will was started on salvage chemotherapy with cytoxan/topotecan. After two cycles of chemotherapy, repeat imaging (MIBG and CT scan) showed essentially stable disease, with no new lesions.

Given the lack of response, Will was started on high-dose chemotherapy, receiving a total of five cycles of chemotherapy (cisplatin/etoposide, adria-VAC, etoposide/ifosfamide, etoposide/carboplatin, adria-VAC). At the completion of therapy, a repeat MIBG and CT scan again showed stable disease at all sites, except a small increase in the size of the nodule at the cardiophrenic junction.

Given his poor response to chemotherapy, we felt that Will was unlikely to have a curative option available. He was initially treated with cytoxan/topotecan (as per POG 9464). He received a total of four courses, and then underwent MIBG therapy at CHOP (12.5 mCi/kg) twice (1/07 and 3/07). He had no significant complications from MIBG and did not require stem cell infusions afterwards. Eight weeks after the second MIBG Will was restaged and had stable disease by both CT scan and MIBG. His urine catechols dropped into the normal range after MIBG therapy and have remained normal since then. Given his stable disease and the desire to continue treatment using agents with a low side effect profile, Will was enrolled on COG ANBL 0621, a phase II trial of ABT-751 on 6/7/07. He tolerated the chemotherapy well, although he had a single dose reduction in his chemotherapy for some neuropathic pain. While on ABT-751 he had stable disease for almost one year. Given the stable disease on minimal treatment, and after extensive discussion with the family the nodule at his cardiophrenic angle was excised on March 2008. Bilateral bone marrow aspirates and biopsies at that time were negative for disease, but unfortunately his pathology of his lesion revealed persistent neuroblastoma. Will continued to have a good clinical response to ABT-751 until he relapsed with a new lesion in his left pleural near the costophrenic angle by CT and MIBG in 6/08.

At this point, Will received a second opinion from Dr. Giselle Sholler at the University of Vermont. After discussions with her the family chose to begin receiving most of their tumor directed therapy under Dr. Sholler’s care at the University of Vermont. Initially, Will was treated with an anti-angiogenic regimen off protocol consisting of vinblastine, rapamycin, celebrex, and lovastatin. This regimen was stopped in approximately in 4/09 with the concern being that Will previously has relapsed after approximately 6-12mo of therapy using other regimens in the past, and therefore Dr. Sholler felt a new regimen may offer Will a more prolonged period of stable disease. At this point (4/09) he was started a regimen consisting of Velcade in combination with oral cytoxan, which he continued for two cycles. In June 2009 he began a Phase I trial consisting of TPI-287 (a novel microtubule inhibitor) in conjunction with temozoloamide at the University of Vermont.

Will is now receiving TPI-287 on a compassionate use basis after finishing the 6 cycles of the phase I study.

Cycle 10 of TPI-287 will begin on Thursday February 11th 2010 and this is Will's 59th cycle of chemo since diagnosis.

The image below shows the location of his primary tumor