Local Anesthesia With General Anesthesia for Pediatric Bone Marrow Procedures.

BACKGROUND: Pediatric patients with cancer undergo repeated painful procedures, including bone marrow aspirations and biopsies (BMABs). Optimal management of procedure-related pain can reduce discomfort, anxiety, and distress. METHODS: Children with neuroblastoma were randomly assigned to 1 of 2 arms on a prospective, single-blind, crossover trial conducted at Memorial Sloan Kettering Cancer Center from October 2016 to January 2018 (www.clinicaltrials.gov, identifier NCT02924324). Participants underwent 2 sequential BMABs: one with general anesthesia (GA) alone, the other with GA plus local anesthesia (LA) (GA + LA). The objective was to assess procedure-related pain and its interference with quality of life (QoL) with GA versus GA + LA. Primary outcome was percentage of participants requiring postprocedural opioids. Secondary outcomes were total opioid and nonopioid analgesics, pain scores, time to first analgesic, QoL, and toxicity. Management of postprocedural pain was standardized. RESULTS: Of 56 participants randomly assigned (3-16.5 years old), 46 completed both procedures. There was no significant difference in percentage of participants requiring opioids with GA versus GA + LA (24% vs 20%, P = .5). Pain scores in the recovery room were significantly lower for GA + LA versus GA (median [IQR]: 0 [0-2] vs 2 [0-4], P = .002). There were no statistically significant differences in total opioid or nonopioid analgesic, 6- and 24-hour pain scores, median time to first analgesic, or pain interference. No adverse events occurred. CONCLUSIONS: LA was associated with significant improvement in pain scores in the immediate recovery period. LA did not reduce postprocedural opioid use, nor did it improve QoL for patients undergoing BMAB with GA.

Intravitreal chemotherapy and laser for newly visible subretinal seeds in retinoblastoma.

BACKGROUND: There has been no effective method for treating newly visible ("new") subretinal seeding in retinoblastoma except enucleation. The objective of this report is to determine whether intravitreal chemotherapy combined with 810 nm indirect laser can successfully treat retinoblastoma eyes with "new" subretinal seeding which appeared after intra-arterial chemotherapy (ophthalmic arterial chemosurgery: OAC). MATERIAL AND METHODS: Single center retrospective study from a tertiary cancer hospital of a case series of 14 eyes treated with combined intravitreal chemotherapy and laser from 2012 to 2017. Ocular salvage, patient survival, recurrence-free ocular survival, metastases, and extraocular extension were assessed. RESULTS: A total of 14 eyes in 13 unilateral or bilateral retinoblastoma patients with "new" subretinal seeding after initial eye salvage therapy were treated with combined intravitreal injection of melphalan (30 ug) or melphalan (30 ug) and topotecan (20 ug) and with 810 nm indirect continuous wave laser. All eyes were salvaged. Only two eyes (14%) recurred again for subretinal seeds after 6 and 8 months, respectively, and required additional cycles of intravitreal injections and laser. Combined intravitreal injection of melphalan or melphalan plus topotecan with 810 nm indirect continuous wave laser was not associated with any metastatic events, patient deaths, extraocular extension, or need for enucleation. CONCLUSION: There has been no effective treatment for "new" subretinal seeding after OAC except enucleation or second course OAC. Combined intravitreal chemotherapy with 810 nm indirect laser may be an effective and safe alternative to enucleation.

Properties and clinical utility of topotecan fluorescence: uses for retinoblastoma.

Topotecan fluoresces when exposed to ultraviolet (UV) light. Our observations with UV light in retinoblastoma cases has allowed us to minimise and manage inadvertent skin contact, guide periocular injections and leakage from such injections and document conjunctival contact after periocular injection in addition to demonstrating the drug in the vitreous after intravitreal injection. The technique is safe, inexpensive and easy to perform.

Randomized trial of hydroxychloroquine for newly diagnosed chronic graft-versus-host disease in children: a Children's Oncology Group study.

The Children's Oncology Group conducted a multicenter Phase III trial for chronic graft-versus-host disease (cGVHD). The double-blind, placebo-controlled, randomized study evaluated hydroxychloroquine added to standard therapy for children with newly diagnosed cGVHD. The study also used a novel grading and response scoring system and evaluated clinical laboratory correlates of cGVHD. The primary endpoint was complete response (CR) after 9 months of therapy. Fifty-four patients (27 on each arm) were enrolled before closure because of slow accrual. The CR rate was 28% in the hydroxychloroquine arm versus 33% in the placebo arm (odds ratio [OR] = 0.77, 95% confidence interval [CI]: 0.20-2.93, P = .75) for 42 evaluable patients. For 41 patients with severity assessment at enrollment, 20 (49%) were severe and 18 (44%) moderate according to the National Institutes of Health Consensus Conference global scoring system. The CR rate was 15% for severe cGVHD and 44% for moderate cGVHD (OR = 0.24, 95% CI: 0.05-1.06, P = .07). Although the study could not resolve the primary question, it provided important information for future cGVHD study design in this population.

Addition of pamidronate to chemotherapy for the treatment of osteosarcoma.

BACKGROUND: This study evaluated the safety and feasibility of the addition of pamidronate to chemotherapy for treatment of osteosarcoma. METHODS: The authors treated 40 patients with osteosarcoma with cisplatin, doxorubicin, and methotrexate with the addition of pamidronate 2 mg/kg/dose (max dose 90 mg) monthly for 12 doses. Survival, event-free survival (EFS), and durability of orthopedic reconstruction were evaluated. RESULTS: For patients with localized disease, event-free survival (EFS) at 5 years was 72% and overall survival 93%. For patients with metastatic disease, EFS at 5 years was 45% and overall survival 64%. Toxicity was similar to patients treated with chemotherapy alone. Thirteen of 14 uncemented implants demonstrated successful osteointegration. Among allograft reconstructions, there were 2 graft failures, 4 delayed unions, and 6 successful grafts. Overall, 5 of 33 reconstructions failed. There were no stress fractures or growth disturbances. CONCLUSIONS: Pamidronate can be safely incorporated with chemotherapy for the treatment of osteosarcoma. It does not impair the efficacy of chemotherapy. Pamidronate may improve the durability of limb reconstruction.

The Memorial Sloan Kettering Cancer Center experience with outpatient administration of high dose methotrexate with leucovorin rescue.

BACKGROUND: We describe the safety and feasibility of an outpatient high dose methotrexate (HDMTX) regimen. METHODS: HDMTX (12 g/m(2)) is administered in a pediatric day hospital (PDH) intravenously (IV) over 4 hrs. Urinary alkalinization is achieved using an IV bolus of sodium bicarbonate and oral bicarbonate tablets. Daily visits to the PDH follow. Leucovorin is begun 24 hrs. after MTX at a standard dose of 10 mg orally (po) every 6 hrs. (q6h). The leucovorin dose is escalated between a range of 20 mg po q6h to 1 g as a continuous IV drip over 24 hrs. according to an institutional algorithm for levels above 10, 1, and 0.1 micromol/L at 24, 48, and 72 hrs. post-MTX. To evaluate our approach, we conducted a retrospective review of all HDMTX courses administered at the Memorial Sloan Kettering Cancer Center between 1996 and 2002. RESULTS: Out of a total of 708 MTX courses, 82% were successfully completed as an outpatient. Forty-nine percent of the MTX courses were treated with standard dose leucovorin while 49% required a dose escalation, the majority of which was to 20-30 mg po q6h. Observed toxicity included mild (Grade 0-I) nephrotoxicity and reversible transaminitis in the majority of patients. Myelosuppression was manifested mainly as neutropenia, with Grade III-IV toxicity in 16% of patients. CONCLUSIONS: Outpatient administration of HDMTX and the required supportive therapy is safe and feasible using the described approach. Approximately half of the patients will require leucovorin dose modification based on serial monitoring of MTX levels.

Methotrexate levels and outcome in osteosarcoma.

BACKGROUND: Peak serum concentrations of methotrexate (MTX) have been reported to correlate with outcome in osteosarcoma (OS). Modification of the MTX dose to achieve peak levels between 700 and 1,000 micromol/L has been recommended. The goal of the study was to assess whether there is a correlation between histologic necrosis of the tumor and/or prognosis with peak MTX serum concentration. PROCEDURE: Treatment included multi-agent adjuvant chemotherapy, including high-dose MTX (12 g/m2). Peak MTX levels were drawn following a 4-hr infusion. Histologic evaluation for percent necrosis was done at the time of definitive resection. RESULTS: The median peak MTX level (n = 52 patients) was 1,060 micromol/L (range: 410-4,700 micromol/L), with significant intra-patient and inter-patient variability. Fifty-eight percent of the levels were 1,000 micromol/L or higher. Response to pre-operative chemotherapy was: 18% Grade I necrosis, 35% Grade II, 31% Grade III, and 16% Grade IV. No significant association was found between the mean peak MTX levels and necrosis (P = 0.44). Event-free survival (EFS) for the 48 patients with non-metastatic disease at diagnosis was 76% at 4 years of follow-up, with no association between the mean peak MTX level and EFS (P = 0.24). CONCLUSIONS: The absence of a demonstrable correlation between peak MTX levels and histologic necrosis or EFS may suggest that most patients achieve therapeutic levels when MTX is given at a dose of 12 g/m(2). The significant degree of intra-patient variability in peak levels poses a dilemma for pharmacokinetic adjustment. Continued use of HD-MTX in all patients, rather than dose adapted therapy, may be justified.