Postoperative Radiotherapy Patterns of Care and Survival Implications for Medulloblastoma in Young Children

Kann, Benjamin H.; Park, Henry S.; Lester-Coll, N.H.; Yeboa, Debra Nana; Benitez, Viviana; Khan, Atif J.; Bindra, Ranjit S.; Marks, Asher; Roberts, Kenneth B.

doi:10.1001/jamaoncol.2016.2547

Cited by 50 publications

(39 citation statements)

References 37 publications

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“…Treatment facilities treating 3 or fewer cases over the time period examined appeared to have worse overall survival compared to centers with more experience. These findings are similar to other studies which demonstrate that patients who receive cancer treatment at lower volume centers have worse survival outcomes [4,8,[15][16][17][18][19][20][21][22]. The majority of these studies, however, tend to report on the relationship between hospital and surgical volume with outcomes [6,[15][16][17][18][19]23], and there are fewer studies investigating radiation or concurrent chemoradiation therapy [4,10,24].…”

Section: Discussionsupporting

confidence: 86%

Impact of Facility Radiation Patient Volume on Overall Survival in Patients with Muscle Invasive Bladder Cancer Undergoing Trimodality Bladder Preservation Therapy

Fischer‐Valuck

Rudra

Gabani

et al. 2019

BLC

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Background: There is an association between higher hospital and urologist case volume and improved survival outcomes for patients with bladder cancer. Less data on facility volume and outcomes exists following trimodality bladder preservation with TURBT followed by definitive chemoradiation (CRT). Materials and Methods: The National Cancer Database was queried for patients from 2004-2013 with urothelial bladder cancer (cT2-4aN0M0) receiving definitive CRT after TURBT. We compared OS between high-and low-bladder preservation case volume (BPCV) centers using Cox proportional hazard models. BPCV was dichotomized into high versus low volume at the 70th percentile level (i.e. high volume defined as top 30th percentile of cases and low volume defined as bottom 70th percentile of cases). Propensity matching was performed to match high-and low-volume centers. Results: A total of 666 treatment facilities treating 1,635 patients with bladder preservation were identified with a median follow-up of 26 months (range, 2-136 months). A 70th percentile cutoff identified 497 patients that received treatment at 64 high-volume facilities. Median OS of patients treated at high BPCV centers was 37.0 months (95% CI, 27.3-46.7) versus 32.3 months (95% CI, 27.9-33.6) for patients treated at low BPCV centers (P = 0.004). High BPCV facilities were independently associated with a decreased hazard of death (HR, 0.86, 95% CI, 0.75-0.98; P = 0.031). In the propensity score matched cohort, median OS of patients treated at high BPCV was 36.1 months (95% CI, 26.5-45.8) versus 28.1 months (95% CI, 23.9-32.3) for patients treated at a low BPCV facility (P = 0.016). Conclusions: In this observational cohort, treatment at a high BPCV facility was associated with improved OS. Causal factors for this finding may include superior bladder specific clinician expertise, technology, and multidisciplinary-care.

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Section: Discussionsupporting

confidence: 86%

Impact of Facility Radiation Patient Volume on Overall Survival in Patients with Muscle Invasive Bladder Cancer Undergoing Trimodality Bladder Preservation Therapy

Fischer‐Valuck

Rudra

Gabani

et al. 2019

BLC

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“…Significant neurocognitive impairment predominates in high-risk patients and young children where experiences with long-term declines in IQ and memory are common due to ongoing nervous system development (Northcott et al, 2019;Ramaswamy et al, 2016). In a study that examined lowering the dosage of radiation to the posterior fossa the results showed worsening patient outcomes, thus radiation exposure remains static (Kann et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Transcriptional control of DNA repair networks by CDK7 regulates sensitivity to radiation in Myc-driven Medulloblastoma

Veo

Danis

Pierce

et al. 2020

Preprint

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Myc-driven Medulloblastoma remains a major therapeutic challenge due to frequent metastasis and a poor 5-year survival rate. Myc gene amplification results in transcriptional dysregulation, proliferation, and survival of malignant cells. To identify therapeutic targets in Myc-amplified medulloblastoma we performed a CRISPR-Cas9 essentiality screen targeting 1140 genes annotated as the druggable genome. CDK7 was identified as a mediator of medulloblastoma tumorigenesis. Using covalent inhibitors and genetic depletion of CDK7 we observe the cessation of tumor growth in xenograft mouse models and increase in apoptotic mechanisms.The results are attributed to repression of a core set of Myc-driven transcriptional programs mediating DNA repair. We further establish that blocking CDK7 activity sensitizes cells to ionizing radiation leading to accrual of DNA damage and extended survival and tumor latency in medulloblastoma xenograft mouse models. Our studies establish a mechanism for selective inhibition of Myc-driven MB by CDK7 inhibition combined with radiation as a viable therapeutic strategy for Myc-amplified medulloblastoma.

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“…Recent analysis by Kann et al analyzed the differing effects of deferred radiation therapy on survival through the NCDB data set (ie, rates of omission of radiation therapy). 32 With a median follow-up of 4.8 years and a studied age group of 3 to 8 years, the researchers discovered that these low rates of radiation therapy utilization were associated with a detriment to survival in this age group (in addition to more advanced disease and treatment at low-volume centers). Interestingly, the only parameters associated with the omission of radiation therapy were younger age and year of diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Outcomes and patterns of care in a nationwide cohort of pediatric medulloblastoma: Factors affecting proton therapy utilization

Kopecký

Khan

Pan

et al. 2017

Advances in Radiation Oncology

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PurposeWe examined national outcomes and patterns of care for pediatric patients with medulloblastoma (MB) in a large observational cohort.Methods and materialsUsing the National Cancer Database, we evaluated the clinical features and survival outcomes of patients diagnosed with MB. The association between intervention, covariables, and outcome was assessed in a multivariable Cox analysis and through logistic regression analysis. Survival was estimated using the Kaplan-Meier method.ResultsAmong the 4032 patients in the National Cancer Database with pediatric brain tumors, 1300 patients met the inclusion criteria of histologic diagnosis, receipt of chemotherapy and radiation, and age ≤18 years. The median age and follow-up were 8.4 years and 4.5 years, respectively. Five-year survival was 79.0%. In the univariate analysis, inferior outcome (overall survival) was associated with rural residence (hazard ratio [HR], 2.78; 95% confidence interval [CI],1.47-5.29; P < .01) and histology (large cell; HR, 1.78; 95% CI,1.08-2.94; P < .05). In multivariable analysis, both remained significant predictors of survival (large cell: HR, 1.68; P < .05; rural residence: HR, 2.74; P < .01). In 2013, the utilization rate of proton therapy (23% of patients) in the United States surpassed intensity modulate radiation therapy (16%), more frequently for patients with higher income (P < .05) or more favorable insurance status (P < .05).ConclusionsAs one of the largest data sets on pediatric MB, the observed variations in treatment intervention and survival outcomes may represent a target for further research.

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Postoperative Radiotherapy Patterns of Care and Survival Implications for Medulloblastoma in Young Children

Cited by 50 publications

References 37 publications

Impact of Facility Radiation Patient Volume on Overall Survival in Patients with Muscle Invasive Bladder Cancer Undergoing Trimodality Bladder Preservation Therapy

Impact of Facility Radiation Patient Volume on Overall Survival in Patients with Muscle Invasive Bladder Cancer Undergoing Trimodality Bladder Preservation Therapy

Transcriptional control of DNA repair networks by CDK7 regulates sensitivity to radiation in Myc-driven Medulloblastoma

Outcomes and patterns of care in a nationwide cohort of pediatric medulloblastoma: Factors affecting proton therapy utilization

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