Kowalchuk, Roman O.

ABSTRACT Purpose We studied histologic Ewing sarcoma (ES) tumor response at local control surgery to explore associations between histologic response and chemotherapy practice changes over time and confirm its prognostic significance in the modern era. Methods We reviewed clinical data for 126 patients with ES treated at Mayo Clinic from 1977 to 2022, analyzing the percentage necrosis as a prognostic factor across chemotherapy regimens (including modern interval‐compressed VDC‐IE). Results In the historical cohort, 5‐year event‐free survival (EFS) and overall survival (OS) for patients with ≤5% versus greater than 5% viable tumor were 76% versus 59% ( p = 0.01) and 83% versus 62% ( p = 0.01). Review of 104 specimens by two pathologists identified the percentage remaining viable tumor as more reproducible than the percentage necrosis and/or fibrosis. On multivariable analysis of patients with localized disease ( n = 87), pelvic tumors and greater than 5% viable tumor remained independent risk factors for poor survival (EFS: hazard ratio [HR] 3.1, p < 0.01; OS: HR 2.1, p = 0.048). The modern cohort consisted of 22 patients. No patients with tumor size less than 8 cm at diagnosis and 100% necrosis after surgery had events; four of seven with tumors greater than 8 cm had events despite 100% necrosis. Conclusions Our results validate the historical threshold of greater than 5% viable tumor with older chemotherapy regimens but not with modern interval‐compressed VDC‐IE. In addition, inter‐rater reliability for the percentage viable is more reproducible than the percentage necrosis. Although numbers are small, tumors less than 8 cm with no viable tumor appear to be a favorable subgroup and suggest risk stratification using a combination of tumor size and any viable tumor should be evaluated in ES.

Abstract Background Vorasidenib is Food and Drug Administration‐approved for treatment of grade 2 isocitrate dehydrogenase (IDH)–mutant gliomas and has demonstrated a benefit in progression‐free survival compared to a placebo. This study assessed the cost‐effectiveness of this treatment strategy compared to standard treatment: observation or chemoradiation (CRT). Methods The authors used an integrated Markov model to compare quality‐adjusted life‐years (QALY) gained and cost‐effectiveness of patients with IDH‐mutated low‐grade glioma (LGG) treated with vorasidenib, observation, or CRT. Outcomes were expressed as incremental cost‐effectiveness ratios (ICERs) per QALY gained. Treatment is considered cost‐effective if it meets the commonly accepted willingness‐to‐pay threshold of $100,000 per QALY gained. Results Based on model parameters, vorasidenib demonstrated an ICER of $356,756 per QALY when compared to CRT. When compared to observation, vorasidenib demonstrated an improved ICER of $215,191 per QALY. On one‐way sensitivity analysis compared to observation, median cost of vorasidenib and median overall survival were most likely to affect ICER with only marginal changes on analysis of other model factors. For ICER to become ≤$100,000 compared to observation, the cost of vorasidenib would need to drop to below $14,072 monthly or have a median survival gain of at least 11.9 years. The probabilistic sensitivity analysis demonstrated that vorasidenib was favored in none of 5000 Monte Carlo iterations. Conclusion Using the best available data, the current price of vorasidenib does not meet commonly accepted cost‐effectiveness thresholds in treatment of IDH‐mutated LGGs.

AbstractBackgroundThis study was aimed at developing and validating a decision‐making tool predictive of overall survival (OS) for patients receiving stereotactic body radiation therapy (SBRT) for spinal metastases.MethodsThree hundred sixty‐one patients at one institution were used for the training set, and 182 at a second institution were used for external validation. Treatments most commonly involved one or three fractions of spine SBRT. Exclusion criteria included proton therapy and benign histologies.ResultsThe final model consisted of the following variables and scores: Spinal Instability Neoplastic Score (SINS) ≥ 6 (1), time from primary diagnosis < 21 months (1), Eastern Cooperative Oncology Group (ECOG) performance status = 1 (1) or ECOG performance status > 1 (2), and >1 organ system involved (1). Each variable was an independent predictor of OS (p < .001), and each 1‐point increase in the score was associated with a hazard ratio of 2.01 (95% confidence interval [CI], 1.79–2.25; p < .0001). The concordance value was 0.75 (95% CI, 0.71–0.78). The scores were discretized into three groups—favorable (score = 0–1), intermediate (score = 2), and poor survival (score = 3–5)—with 2‐year OS rates of 84% (95% CI, 79%–90%), 46% (95% CI, 36%–59%), and 21% (95% CI, 14%–32%), respectively (p < .0001 for each). In the external validation set (182 patients), the score was also predictive of OS (p < .0001). Increasing SINS<zaq;6> was predictive of decreased OS as a continuous variable (p < .0001).ConclusionsThis novel score is proposed as a decision‐making tool to help to optimize patient selection for spine SBRT. SINS may be an independent predictor of OS.

BackgroundPatients with high‐risk prostate cancer (HRPC) have multiple accepted treatment options. Because there is no overall survival benefit of one option over another, appropriate treatment must consider patient life expectancy, quality of life, and cost.MethodsThe authors compared quality‐adjusted life years (QALYs) and cost effectiveness among treatment options for HRPC using a Markov model with three treatment arms: (1) external‐beam radiotherapy (EBRT) delivered with 20 fractions, (2) EBRT with 23 fractions followed by low‐dose‐rate (LDR) brachytherapy boost, or (3) radical prostatectomy alone. An exploratory analysis considered a simultaneous integrated boost according to the FLAME trial (ClinicalTrials.gov identifier NCT01168479).ResultsTreatment strategies were compared using the incremental cost‐effectiveness ratio (ICER). EBRT with LDR brachytherapy boost was a cost‐effective strategy (ICER, $20,929 per QALY gained). These results were most sensitive to variations in the biochemical failure rate. However, the results still demonstrated cost effectiveness for the brachytherapy boost paradigm, regardless of any tested parameter ranges. Probabilistic sensitivity analysis demonstrated that EBRT with LDR brachytherapy was favored in 52% of 100,000 Monte Carlo iterations. In an exploratory analysis, EBRT with a simultaneous integrated boost was also a cost‐effective strategy, resulting in an ICER of $62,607 per QALY gained; however, it was not cost effective compared with EBRT plus LDR brachytherapy boost.ConclusionsEBRT with LDR brachytherapy boost may be a cost‐effective treatment strategy compared with EBRT alone and radical prostatectomy for HRPC, demonstrating high‐value care. The current analysis suggests that a reduction in biochemical failure alone can result in cost‐effective care, despite no change in overall survival.

Particle therapy has received increasing attention in the treatment of breast cancer due to its unique physical properties that may enhance patient quality of life and reduce the late effects of therapy. In this review, we will examine the rationale for the use of proton and carbon therapy in the treatment of breast cancer and highlight their potential for sparing normal tissue injury. We will discuss the early dosimetric and clinical studies that have been pursued to date in this domain before focusing on the remaining open questions limiting the widespread adoption of particle therapy.