PROGRESS/FOLLOWUP NOTE - 06/05/2009
Neuroblastoma.
HISTORIAN
Father
HISTORY OF PRESENT ILLNESS
Will is a known patient with refractory neuroblastoma, who continues to do well without any concerns; a past medical history of neuroblastoma is below. William recently completed two cycles of velcade and oral Cytoxan chemotherapy which he complete on May 5th, 2009. He tolerated those chemotherapies but had some vomiting and weight loss. He currently has no pain and is very active and playful. He is currently eating very well, with stable weight. No problems sleeping. No fevers. No concerns for infection.
REVIEW OF SYSTEMS
He is active and playful, with no concerns neurologically. No cardiovascular or respiratory concerns. No shortness of breath. No abdominal pain. No diarrhea, and no constipation, eating well. No musculoskeletal concerns; very active and playful, able to run, jump, and play. On his skin he does have two small molluscum near is elbow, no other rashes or concerns.
PAST MEDICAL HISTORY
Will is a 4-year-old boy with relapsed neuroblastoma which initially presented as an infant in 03/05, with left-sided supraclavicular node, left arm and facial swelling, and left-sided Horner's. CT showed multiple cervical lymph nodes, with a large posterior mediastinal mass, along the spinal column; MRI invades at theneuronal foramina. Bone scan showed no bone lesions at that time. MIBG showed uptake in the left mediastinum, and supraclavicular lesion. There was also a small MIBG avid lesion in the left humerus which initially was not identified, but was re-reviewed and identified at relapse. Bone marrows at that time were negative for disease. Tumor markers were mildly elevated and MYCN was non-amplified, histology was not favorable. LDH was normal. Ferritin was slightly elevated at 119. He was classified as a stage III intermediate risk neuroblastoma with unfavorable biology.
Although based upon re-review of the arm lesion would have classified him as a stage IV intermediate risk with unfavorable biology. He was enrolled in COG protocol, POG 3961, and received eight cycles of chemotherapy. While he had a good initial response to chemotherapy after two cycles, the following four cycles shows his mass unchanged. The decision was made at that time to continue with local control by surgery, and he underwent debulking procedure in August of 2005, after his six cycles of chemotherapy. As much tumor as possible was resected, while maintaining the brachial plexus. Pathology revealed intermixed mature and immature neuroblastoma. He received two more cycles of chemotherapy under therapy, CT scan showed a residual posterior mediastinal mass which remained MIBG avid, stable left arm lesion, and left humerus, and no other disease.
He went off of therapy in October of 2005, and classified as a very good partial response. He had a routine followup scan in 02/06; there was interval enlargement of the primary mass, as well as a new left internal mammary adenopathy and new left jugular adenopathy. MIBG revealed these lesions to be MIBG avid, and a new abdominal lesion nearthe splenic flexure, which did not correlate by CT scan. Will went to the operating room on 03/20/06, where he had removal of the posterior jugular and internal mammary adenopathy and biopsy of the residual posterior mediastinal mass, which confirmed recurrent neuroblastoma, with the same biology. Both lymph nodes and the residual mass, bone marrow aspirate and biopsy were negative. Postop repeat CT scan revealed new pleural based nodules.
Will was started on salvage chemotherapy with Cytoxan and topotecan after two cycles of chemotherapy. Repeat imaging showed stable disease with no new lesions. Given the lack of response, Will was started on high dose chemotherapy, receiving five cycles of chemotherapy of cisplatin and etoposide, Adriavac, etoposide/Ifosfamide, etoposide/carboplatin, Adriavac. At the completion of therapy, MIBG scan again showed stabilization with a small increase in the size of the nodule at the cardiophrenic junction. Will was very sick during this time, and given his poor response to chemotherapy, Will was determined to not have a curative option at this point.
He was then begun on palliative chemotherapy with Cytoxan, topotecan, per POG 9464, with dose decreased to 4 days instead of 5, due to marrow toxicity. He received a total of four courses, and then underwent MIBG therapy with CHOP twice, 12.5 millicuries per kg, in January of 2007, and March of 2007. He tolerated MIBG well; eight weeks after the second MIBG, he was restaged, and had stable disease by both CT and MIBG. Urine calculations dropped into the normal range after MIBG therapy and have remained normal since. Given his stable disease and desire to continue treatment using agents with low side effect profile, he was enrolled on COG protocol of a safety trial of ABT 751, on June 7th, 2007. He tolerated this chemotherapy very well, had single dose reduction for neuropathic pain, and he was on ABT 751, had stable disease for almost a year.
Given stable disease and minimal treatment, after extensive discussion with the family, the nodule on his cardiophrenic angle was excised in March of 2008. Bilateral bone marrow aspirates and biopsies were negative, but this pathology of this lesion revealed persistent neuroblastoma. Will remained on ABT 751 for one year, and in July of 2008, came to the University of Vermont for consultation and we discussed further options, due to the lack responsiveness to chemotherapy Will did not enter the Phase II Nifurtimox trial. We discussed other therapeutic options and was placed on vinblastine, rapamycin therapy receiving vinblastine weekly and rapamycin daily, per Dr. Barichel's treatment protocol from Sick Kids in Toronto.
Will received ten cycles, each cycle being one month of vinblastine, and rapamycin, and then in February of 2009, had an MIBG CT scan done here at Vermont, and again showed stable disease. Bone marrow biopsy and aspirates were negative. We discussed theresults and plan to continue vinblastine and rapamycin until April of 2009. Will had croup, held rapamycin and was admitted to Boston Children's Hospital for respratory distress. This resolved over a few days. Upon discharge, discussed with Dr. Rao, and Mr. Lacey, and changing therapy to Velcade 1.3 mg per meter squared on day #1, 4, 8 and Cytoxan 100 mg per meter squared daily for 14 days, on a 21-day cycle.
Will had significant nausea with this regimen. During the second cycle, we decreased the Cytoxan to 50 mg per meter squared, which improved his nausea, but still did not feel well during the chemotherapy week. He has been off of therapy since May 5th, 2009, and is now here to enroll in TPI trial. Will was seen yesterday in the clinic, and the informed consent was reviewed with his father and he was given the opportunity to ask all questions and discussed the risks and benefits of possible toxicities, and father consented to enroll in the study. MIBG scans were done yesterday, which showed stable disease of his mediastinal mass, and bone marrow biopsy and aspirate were done, which were negative.
He was given Decadron to enroll in trial, and will begin TPI today.
FAMILY HISTORY
Noncontributory for cancers.
SOCIAL HISTORY
He lives with mother and father, in Braintree, Massachusetts. He has two younger sisters, one born one week ago, and one 18 months.
PHYSICAL EXAM
Vital signs had a heart rate of 108, blood pressure 115/54, temperature 36.2, weight 26.5, height 117.7 cm.
General: In general is well appearing, well developed, well nourished, in no acute distress. Eyes - sclerae are white. Conjunctivae clear. Pupils are equal and reactive. HEENT has mucous membranes. Lips are pink and symmetrical. No oral ulcers. No thrush. Chest: Port is in place in the chest. Respirations even and unlabored. Lungs are clear. No adventitious sounds bilaterally. Heart is regular rate and rhythm, perfusion is normal. Non tachycardic. No murmurs. No edema, 2+ pulses. Abdomen is soft, nontender, and nondistended. Active bowel sounds. Liver and spleen are without tenderness or enlargement. Lymph nodes - not palpably enlarged nodes in the neck, axillary, inguinal, or supraclavicular areas. Skin is warm, dry, with normal turgor, no rashes, no lesionsexcept for two dots of molluscum near the elbow. Neurological - cranial nerves are intact II-XII, except for slight ptosis of the left eye. He is developmentally appropriate for age. Cerebellar: Finger-to-nose appropriate. Appropriate touch and pain sensation. Psychiatric: He is alert and oriented times three, with an appropriate affect. Musculoskeletal: Gait is coordinated and smooth. Strength is 5/5 in all extremities. No muscular atrophy or weakness.
His labs were done yesterday, which shows an AST of 41, ALT of 52, LDH is 820, ferritin is 296, white count is 4.95, with an ANC of 2,270. Hemoglobin is 10.6, and platelets are 222,000. Sodium is 137, potassium is 4.0, chloride is 105, bicarbonate is 27.
MIBG CT scan shows positive stable disease in the mediastinal area. Bone marrows are negative.
IMPRESSION
This is a 4-year-old male with refractory neuroblastoma, here for enrollment on TPI trial to begin baseline study this morning.
1.Oncology to start TPI at 110 mg per meter squared IV today. Father gave Decadron premedications at 9 p.m. and 3 a.m. and at 9 a.m. this morning. Will begin TPI infusion, premedications to include Decadron, Benadryl, ranitidine, and Zofran. Patient was observed throughout the TPI infusion this morning and tolerated the infusion well with no complications.
2. Pain is no issue currently.
3. ID - on Bactrim for PCP prophylaxis. No concerns for any significant infection at this time.
4. FEN: Fluids, electrolytes, and nutrition - eating well with no concerns. Electrolytes stable.
5. Heme - stable CBC, is normal. Patient is not transfusion dependent.
6. Followup will be in one week for day #8 of TPI infusion.
