Matthew T. Ballo

The initial favorable efficacy and safety profile for Alpha DaRT have been demonstrated (NCT04377360); however, the longer-term safety and durability of the treatment are unknown. This pooled analysis of four prospective trials evaluated the long-term safety and efficacy of Alpha DaRT for the treatment of head and neck or skin tumors. A total of 81 lesions in 71 patients were treated across six international institutions, with a median follow-up of 14.1 months (range: 2–51 months). Alpha DaRT sources were delivered via a percutaneous interstitial technique and placed to irradiate the tumor volume with the margin. The sources were removed two to three weeks following implantation. A complete response was observed in 89% of treated lesions (n = 72) and a partial response in 10% (n = 8). The two-year actuarial local recurrence-free survival was 77% [95% CI 63–87]. Variables, including recurrent versus non-recurrent lesions, baseline tumor size, or histology, did not impact long-term outcomes. Twenty-seven percent of patients developed related acute grade 2 or higher toxicities, which resolved with conservative measures. No grade 2 or higher late toxicities were observed. These data support the favorable safety profile of Alpha DaRT, which is currently being explored in a pivotal US trial.

Tumour Treating Fields (TTFields) are electric fields that disrupt processes required for cancer cell viability and tumour progression. TTFields therapy gained FDA approval and CE accreditation for newly diagnosed glioblastoma (ndGBM) following the EF-14 study (NCT00916409). We aimed to determine the real-world survival benefit of TTFields therapy. Survival data from clinical studies in TTFields therapy-treated patients with ndGBM were identified using a literature search and analysed. The Cochran Q test and Higgins I2 statistic were used to assess and quantify inter-study heterogeneity. Survival curves were pooled using a distribution-free random-effects method. Among studies evaluating the clinical effcacy of TTFields therapy in ndGBM, six studies were identified which compared the addition of TTFields therapy to standard of care (SOC) vs SOC alone. The meta-analysis showed a significant improvement in OS for TTFields therapy-treated patients vs SOC alone (P < 0.001). The pooled effect was robust and independent of any individual study. In post-approval studies, the pooled median OS was 22.2 months (95% CI, 17.3–42.6) and 17.3 months (95% CI, 13.6–22.0) for TTFields therapy-treated patients and SOC, respectively. Rates of gross total resection were generally higher in the real-world setting, irrespective of TTFields therapy use. Average device usage of ≥75% was associated with prolonged survival vs <75% usage (pooled HR: 0.63; 95% CI, 0.48–0.83; P = 0.001). Data suggest a significant survival benefit when TTFields therapy is added to SOC for patients with ndGBM. Usage of ≥75% may be meaningful in the real-world setting.

(1) Background: The objective of this analysis was to evaluate the device usage rates and patterns of use regarding Tumor-Treating Fields (TTFields) for patients with malignant pleural mesothelioma (MPM) throughout the US. (2) Methods: We evaluated de-identified data from 33 patients with MPM enrolled in FDA-required HDE protocols at 14 institutions across the US from September 2019 to March 2022. (3) Results: The median number of total TTFields usage days was 72 (range: 6–649 days), and the total treatment duration was 160 months for all patients. A low usage rate (defined as less than 6 h per day, 25%) was observed in 34 (21.2%) months. The median TTFields usage in the first 3 months was 12 h per day (range: 1.9–21.6 h), representing 50% (range: 8–90%) of the potential daily duration. The median TTFields usage after 3 months decreased to 9.1 h per day (range: 3.1–17 h), representing 38% (range: 13–71%) of the daily duration, and was lower than usage in the first 3 months (p = 0.01). (4) Conclusions: This study represents the first multicenter analysis of real-world TTFields usage based on usage patterns for MPM patients in clinical practice. The real-world usage level was lower than the suggested daily usage. Further initiatives and guidelines should be developed to evaluate the impact of this finding on tumor control.

Background: Determinates of tumor treating fields (TTFields) usage in patients receiving combined modality therapy for primary IDH wild-type glioblastoma are currently unknown. Methods: Ninety-one patients underwent maximal debulking surgical resection, completed external beam radiotherapy with concurrent Temozolomide (TMZ), and initiated adjuvant TMZ with or without TTFields. We performed a retrospective analysis of patient, tumor, and treatment-related factors that affected TTFields usage. Results: We identified three TTFields usage subgroups: 32 patients that declined TTFields, 40 patients that started, but had monthly compliance of less than 75% or used it for less than 2 months, and 19 patients who used TTFields for 2 or more months and maintained average monthly compliance greater than 75%. With 26.5 months median follow-up for surviving patients, the 1- and 3-year actuarial overall survival for all patients was 80% and 18%, respectively. On multivariate analysis TTFields use (P = .03), extent of surgical resection (P = 0.02), and MGMT methylation status (P = .01) were significantly associated with overall survival. TTFields usage was explored as a continuous variable and higher average usage was associated with longer overall survival (P = .03). There was no relationship between patient, tumor, or treatment-related factors and a patient’s decision to use TTFields. Conclusions: No subgroup of patients was more or less likely to initiate TTFields therapy and no subgroup was more or less likely to use TTFields as prescribed. The degree of TTFields compliance may be associated with improved survival independent of other factors.

Tumor-treating fields (TTFields) are a noninvasive antimitotic cancer treatment consisting of low-intensity alternating electric fields delivered to the tumor or tumor bed via externally applied transducer arrays. In multiple in vitro and in vivo cancer cell lines, TTFields therapy inhibits cell proliferation, disrupts cell division, interferes with cell migration and invasion, and reduces DNA repair. Human trials in patients with primary glioblastoma showed an improvement in overall survival, and trials in patients with unresectable malignant pleural mesothelioma showed favorable outcomes compared with historical control. This led to U.S. Food and Drug Administration approval in both clinical situations, paving the way for development of trials investigating TTFields in other malignancies. Although these trials are ongoing, the existing evidence suggests that TTFields have activity outside of neuro-oncology, and further study into the mechanism of action and clinical activity is required. In addition, because TTFields are a previously unrecognized antimitotic therapy with a unique mode of delivery, the oncological community must address obstacles to widespread patient and provider acceptance. TTFields will likely join surgery, systemic therapy, and radiation therapy as a component of multimodality management of patients with solid malignancies. Implications for Practice: Tumor-treating fields (TTFields) exhibit a broad range of antitumor activities. Clinically, they improve overall survival for patients with newly diagnosed glioblastoma. The emergence of TTFields has changed the treatment regimen for glioblastoma. Clinicians need to understand the practical issues surrounding its use in the multidisciplinary management of patients with glioblastoma. With ongoing clinical trials, TTFields likely will become another treatment modality for solid malignancies.

In Reply We are pleased by the interest of Schernberg and colleagues in our analysis of the association of definitive pelvic radiation therapy with survival amo