Phase II trial of proton therapy versus photon IMRT for GBM: secondary analysis comparison of progression-free survival between RANO versus clinical assessment.

BACKGROUND: This secondary image analysis of a randomized trial of proton radiotherapy (PT) versus photon intensity-modulated radiotherapy (IMRT) compares tumor progression based on clinical radiological assessment versus Response Assessment in Neuro-Oncology (RANO). METHODS: Eligible patients were enrolled in the randomized trial and had MR imaging at baseline and follow-up beyond 12 weeks from completion of radiotherapy. "Clinical progression" was based on a clinical radiology report of progression and/or change in treatment for progression. RESULTS: Of 90 enrolled patients, 66 were evaluable. Median clinical progression-free survival (PFS) was 10.8 (range: 9.4-14.7) months; 10.8 months IMRT versus 11.2 months PT (P = .14). Median RANO-PFS was 8.2 (range: 6.9, 12): 8.9 months IMRT versus 6.6 months PT (P = .24). RANO-PFS was significantly shorter than clinical PFS overall (P = .001) and for both the IMRT (P = .01) and PT (P = .04) groups. There were 31 (46.3%) discrepant cases of which 17 had RANO progression more than a month prior to clinical progression, and 14 had progression by RANO but not clinical criteria. CONCLUSIONS: Based on this secondary analysis of a trial of PT versus IMRT for glioblastoma, while no difference in PFS was noted relative to treatment technique, RANO criteria identified progression more often and earlier than clinical assessment. This highlights the disconnect between measures of tumor response in clinical trials versus clinical practice. With growing efforts to utilize real-world data and personalized treatment with timely adaptation, there is a growing need to improve the consistency of determining tumor progression within clinical trials and clinical practice.

Young Adult Populations Face Yet Another Barrier to Care With Insurers: Limited Access to Proton Therapy.

PURPOSE: Young patients, including pediatric, adolescent, and young adult (YA) patients, are most likely to benefit from the reduced integral dose of proton beam radiation therapy (PBT) resulting in fewer late toxicities and secondary malignancies. This study sought to examine insurance approval and appeal outcomes for PBT among YA patients compared with pediatric patients at a large-volume proton therapy center. METHODS AND MATERIALS: We performed a cross-sectional cohort study of 284 consecutive patients aged 0 to 39 years for whom PBT was recommended in 2018 through 2019. Pediatric patients were defined as aged 0 to 18 years and YA patients 19 to 39 years. Rates of approval, denials, and decision timelines were calculated. Tumor type and location were also evaluated as factors that may influence insurance decisions. RESULTS: A total of 207 patients (73%) were approved for PBT at initial request. YA patients (n = 68/143, 48%) were significantly less likely to receive initial approval compared with pediatric patients (n = 139/141; 99%) (P < .001). Even after 47% (n = 35 of 75) of the PBT denials for YA patients were overturned, YAs had a significantly lower final PBT approval (72% vs pediatric 99%; P < .001). The median wait time was also significantly longer for YA patients (median, 8 days; interquartile range [IQR] 3-17 vs median, 2 days; IQR, 0-6; P < .001). In those patients requiring an appeal, the median wait time was 16 days (IQR, 9-25). CONCLUSION: Given the decades of survivorship of YA patients, PBT is an important tool to reduce late toxicities and secondary malignancies. Compared with pediatric patients, YA patients are significantly less likely to receive insurance approval for PBT. Insurance denials and subsequent appeal requests result in significant delays for YA patients. Insurers need to re-examine their policies to include expedited decisions and appeals and removal of arbitrary age cutoffs so that YA patients can gain easier access to PBT. Furthermore, consensus guidelines encouraging greater PBT access for YA may be warranted from both medical societies and/or AYA experts.

Timing of Local Therapy Affects Survival in Ewing Sarcoma.

PURPOSE: We aimed to investigate the relationship between survival and time to local therapy after initiation of up-front chemotherapy in the treatment of patients with localized Ewing sarcoma. METHODS AND MATERIALS: The National Cancer Database was queried for patients with localized Ewing sarcoma treated with primary chemotherapy and subsequent local therapy. Kaplan-Meier survival curves were generated for patients initiating local therapy 6 to 15 weeks and ≥16 weeks after chemotherapy initiation. Multivariable binomial logistic regression was used to identify factors associated with prolonged time to local therapy. A multivariable Cox proportional hazards model was used to identify factors associated with overall survival (OS). RESULTS: The final cohort included 1318 patients. A higher proportion of patients initiating local therapy 6 to 15 weeks after chemotherapy initiation versus ≥16 weeks after chemotherapy initiation were ≤21 years old (79.5% vs 72.0%; P = .004). Age >21 years (P < .001; hazard ratio, 1.65; 95% confidence interval, 1.28-2.12), tumor size >8 cm (P = .016), and time to local therapy ≥16 weeks (P = .005; hazard ratio, 1.41; 95% confidence interval, 1.11-1.80) were associated with reduced OS; after review of margin status, negative margins were associated with improved OS compared with gross disease (P = .029). Patients initiating local therapy at 6 to 15 weeks versus ≥16 weeks had a 5-year OS of 78.7% versus 70.4% and a 10-year OS of 70.3% versus 57.1%, respectively (P < .001). The difference in OS according to time to local therapy was particularly more important in patients receiving radiation therapy alone. Age >21 years and treatment by radiation therapy alone were associated with delayed time (>16 weeks) to local therapy, whereas private insurance and income >$48,000 were less likely to be associated with delayed local therapy. CONCLUSIONS: Delayed time to local therapy ≥16 weeks after chemotherapy initiation was independently associated with worse survival in patients with localized Ewing sarcoma.

Proton therapy for pediatric malignancies: Fact, figures and costs. A joint consensus statement from the pediatric subcommittee of PTCOG, PROS and EPTN.

Radiotherapy plays an important role in the management of childhood cancer, with the primary aim of achieving the highest likelihood of cure with the lowest risk of radiation-induced morbidity. Proton therapy (PT) provides an undisputable advantage by reducing the radiation 'bath' dose delivered to non-target structures/volume while optimally covering the tumor with tumoricidal dose. This treatment modality comes, however, with an additional costs compared to conventional radiotherapy that could put substantial financial pressure to the health care systems with societal implications. In this review we assess the data available to the oncology community of PT delivered to children with cancer, discuss on the urgency to develop high-quality data. Additionally, we look at the advantage of combining systemic agents with protons and look at the cost-effectiveness data published so far.