Local Control With 21-Gy Radiation Therapy for High-Risk Neuroblastoma

Purpose To analyze the renal function outcomes in patients undergoing radiation therapy for neuroblastoma. Methods and Materials The clinical metrics of renal function were analyzed in patients undergoing radiation therapy for high-risk neuroblastoma from 2000 to 2015. The blood urea nitrogen (BUN) and creatinine values before radiation therapy were compared with last available follow-up values and analyzed with the clinical circumstances, including follow-up length, age at primary irradiation, nephrectomy, and radiation technique. The creatinine clearance was estimated using the Shull method. Results With a median follow-up period of 3.5 years, none of the 266 patients studied developed a chronic renal insufficiency. For all patients, the creatinine level increased from 0.44 to 0.51 mg/dL and the BUN increased from 10.53 to 15.52 mg/dL. Three patients required antihypertensive medication. The patients who underwent intensity modulated radiation therapy did not experience increased creatinine levels during the follow-up period; however, they had a reduced median follow-up length compared with patients treated with anteroposterior/posteroanterior beams (4.7 vs 3.3 years). A longer follow-up length was associated with an increased creatinine level. The preradiation therapy creatinine level increased with patient age, similar to that of the last follow-up creatinine level, suggesting that the changes in creatinine could likely be explained by physiologic increases associated with aging rather than radiation-induced renal damage. The creatinine clearance did not decrease in any circumstance. Conclusions The present cohort had excellent renal outcomes after radiation therapy for neuroblastoma. No patient developed chronic renal insufficiency, and the small increases in BUN and creatinine we observed correlated, as expected, with increases in patient age. The results of the present study revealed a possible advantage for intensity modulated radiation therapy in preserving renal function; however, the follow-up length is a recognized confounding variable. The kidneys are vital structures to consider when planning radiation therapy for neuroblastoma patients, and we have found encouraging evidence that modern techniques to spare them in the setting of multiple treatment-related insults have been successful.

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“…All patients had undergone chemotherapy before RT, as previously described (11). The systemic therapy exposures are summarized in Table 2.…”

Section: Resultsmentioning

confidence: 99%

Renal Function Outcomes of High-risk Neuroblastoma Patients Undergoing Radiation Therapy

Beckham

Casey

LaQuaglia

et al. 2017

International Journal of Radiation Oncology*Biology*Physics

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“…Local control is inherently a part of curative therapy, and RT following surgical resection is a necessary component. Radiation therapy is most commonly tasked with controlling microscopic disease, because GTR is achievable in the majority of cases, and for this purpose, RT doses between 21 and 24 Gy seem to be effective (4, 6–9, 11, 22). Historically, consensus favored improved outcomes with either greater than 90% resection or GTR (23–26), though other authors have found no relation to extent of resection (5, 27–29), leaving uncertainty regarding how to compensate when residual tissue remains.…”

Section: Discussionmentioning

confidence: 99%

“…Hyperfractionation (9, 12) and proton therapy (33) have also been means by which attempts have been made to mitigate late toxicities. With the sort of radiosensitivity that our series and others suggest, allowing for most RT courses to be limited to 21.6 Gy, it may be that modern, more-expensive techniques would practically provide no clinical advantage.…”

Section: Discussionmentioning

confidence: 99%

“…Cure was a rarity in historical series (1–3), but with advancement of aggressive multimodal therapy, rates of progression-free survival often approach or exceed 50% (4–9). Given the inherent toxicities of radiating pediatric patients, and because systemic failure remains the obstacle to cure in the vast majority of failures (4, 5, 10, 11), minimizing dosage of consolidative radiation therapy (RT) to the primary site after surgical resection remains a valid concern.…”

Section: Introductionmentioning

confidence: 99%

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Favorable Local Control From Consolidative Radiation Therapy in High-Risk Neuroblastoma Despite Gross Residual Disease, Positive Margins, or Nodal Involvement

Ferris

Danish

Switchenko

et al. 2017

International Journal of Radiation Oncology*Biology*Physics

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Purpose To report the influence of radiation therapy (RT) dose and surgical pathology variables on disease control and overall survival (OS) in patients treated for high-risk neuroblastoma at a single institution. Methods and Materials We conducted a retrospective study of 67 high-risk neuroblastoma patients who received RT as part of definitive management from January 2003 until May 2014. Results At a median follow-up of 4.5years, 26patients (38.8%) failed distantly; 4 of these patients also failed locally. One patient progressed locally without distant failure. Local control was 92.5%, and total disease control was 59.5%. No benefit was demonstrated for RT doses over 21.6 Gy with respect to local relapse—free survival (P = .55), disease-free survival (P = .22), or OS (P= .72). With respect to local relapse—free survival, disease-free survival, and OS, no disadvantage was seen for positive lymph nodes on surgical pathology, positive surgical margins, or gross residual disease. Of the patients with gross residual disease, 75% (6 of 8) went on to have no evidence of disease at time of last follow-up, and the 2 patients who failed did so distantly. Conclusions Patients with high-risk neuroblastoma in this series maintained excellent local control, with no benefit demonstrated for radiation doses over 21.6 Gy, and no disadvantage demonstrated for gross residual disease after surgery, positive surgical margins, or pathologic lymph node positivity. Though the limitations of a retrospective review for an uncommon disease must be kept in mind, with small numbers in some of the subgroups, it seems that dose escalation should be considered only in exceptional circumstances.

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“…[1][2][3] Our institution and others have previously shown that a dose of 21 Gy RT provides excellent local control after gross total resection (GTR). [4][5][6][7] Although local failure (LF) is <10% among patients treated with 21 Gy RT after GTR, locoregional recurrence is much Abbreviations: CTV, clinical target volume; EFS, event-free survival; GTR, gross total resection; LF, local failure; MSK, Memorial Sloan Kettering; OS, overall survival; RT, radiation therapy more common among patients with macroscopic residual disease after surgical resection, with local recurrence rates approaching 50%. 8 There are no randomized trials that have directly addressed the role and optimal dose of RT to the primary site in high-risk neuroblastoma.…”

Section: Introductionmentioning

confidence: 99%