Introduction: The aim of this systematic review was to summarize the current literature on wearable technologies in oncology patients for the purpose of prognostication, treatment monitoring, and rehabilitation planning. Methods: A search was conducted in Medline ALL, Cochrane Central Register of Controlled Trials, Embase, Emcare, CINAHL, Scopus, and Web of Science, up until February 2022. Articles were included if they reported on consumer grade and/or non-commercial wearable devices in the setting of either prognostication, treatment monitoring or rehabilitation. Results: We found 199 studies reporting on 18 513 patients suitable for inclusion. One hundred and eleven studies used wearable device data primarily for the purposes of rehabilitation, 68 for treatment monitoring, and 20 for prognostication. The most commonly-reported brands of wearable devices were ActiGraph (71 studies; 36%), Fitbit (37 studies; 19%), Garmin (13 studies; 7%), and ActivPAL (11 studies; 6%). Daily minutes of physical activity were measured in 121 studies (61%), and daily step counts were measured in 93 studies (47%). Adherence was reported in 86 studies, and ranged from 40% to 100%; of these, 63 (74%) reported adherence in excess of 80%. Conclusion: Wearable devices may provide valuable data for the purposes of treatment monitoring, prognostication, and rehabilitation. Future studies should investigate live-time monitoring of collected data, which may facilitate directed interventions.

Radiotherapy (RT) is a key component of cancer treatment. Most of the time, radiation is given after surgery but for soft-tissue sarcomas (STS), pre-surgical radiation is commonly utilized. However, despite improvements in RT accuracy, the rate of local recurrence remains high and is the major cause of death for patients with STS. A better understanding of cell fates in response to RT could provide new therapeutic options to enhance tumour cell killing by RT and facilitate surgical resection. Here, we showed that irradiated STS cell cultures do not die but instead undergo therapy-induced senescence (TIS), which is characterized by proliferation arrest, senescence-associated β-galactosidase activity, secretion of inflammatory cytokines and persistent DNA damage. STS-TIS was also associated with increased levels of the anti-apoptotic Bcl-2 family of proteins which rendered cells targetable using senolytic Bcl-2 inhibitors. As oppose to radiation alone, the addition of senolytic agents Venetoclax (ABT-199) or Navitoclax (ABT-263) after irradiation induced a rapid apoptotic cell death in STS monolayer cultures and in a more complex three-dimensional culture model. Together, these data suggest a new promising therapeutic approach for sarcoma patients who receive neoadjuvant RT. The addition of senolytic agents to radiation treatments may significantly reduce tumour volume prior to surgery and thereby improve the clinical outcome of patients.

The efficacy of immunotherapy targeting the PD-1/PD-L1 pathway has previously been demonstrated in metastatic head and neck squamous cell carcinoma (HNSCC). Stereotactic Body Radiotherapy (SBRT) aims at ablating metastatic lesions and may play a synergistic role with immunotherapy. The purpose of this study is to assess the safety and efficacy of triple treatment combination (TTC) consisting of the administration of durvalumab and tremelimumab in combination with SBRT in metastatic HNSCC. This is a phase I/II single arm study that will include 35 patients with 2–10 extracranial metastatic lesions. Patients will receive durvalumab (1500 mg IV every 4 weeks (Q4W)) and tremelimumab (75 mg IV Q4W for a total of 4 doses) until progression, unacceptable toxicity or patient withdrawal. SBRT to 2–5 metastases will be administered between cycles 2 and 3 of immunotherapy. The safety of the treatment combination will be evaluated through assessment of TTC-related toxicities, defined as grade 3–5 toxicities based on Common Terminology Criteria for Adverse Events (v 4.03), occurring within 6 weeks from SBRT start, and that are definitely, probably or possibly related to the combination of all treatments. We hypothesize that dual targeting of PD-L1 and CTLA-4 pathways combined with SBRT will lead to < 35% grade 3–5 acute toxicities related to TTC. Progression free survival (PFS) will be the primary endpoint of the phase II portion of this study and will be assessed with radiological exams every 8 weeks using the RECIST version 1.1 criteria. The combination of synergistic dual checkpoints inhibition along with ablative radiation may significantly potentiate the local and systemic disease control. This study constitutes the first clinical trial combining effects of SBRT with dual checkpoint blockade with durvalumab and tremelimumab in the treatment of metastatic HNSCC. If positive, this study would lead to a phase III trial testing this treatment combination against standard of care in metastatic HNSCC. NCT03283605 . Registration date: September 14, 2017; version 1.

Cancer therapy has evolved to a more targeted approach and often involves drug combinations to achieve better response rates. Non-thermal plasma (NTP), a technology rapidly expanding its application in the medical field, is a near room temperature ionized gas capable of producing reactive species, and can induce cancer cell death both in vitro and in vivo. Here, we used proliferation assay to characterize the plasma sensitivity of fourteen breast cancer cell lines. These assays showed that all tested cell lines were sensitive to NTP. In addition, a good correlation was found comparing cell sensitivity to NTP and radiation therapy (RT), where cells that were sensitive to RT were also sensitive to plasma. Moreover, in some breast cancer cell lines, NTP and RT have a synergistic effect. Adding a dose of PARP-inhibitor olaparib to NTP treatment always increases the efficacy of the treatment. Olaparib also exhibits a synergistic effect with NTP, especially in triple negative breast cancer cells. Results presented here help elucidate the position of plasma use as a potential breast cancer treatment.

Background: Anti-PD-1 has activity in brain metastases (BM). This phase II open labeled non-randomized single arm trial examined the safety and efficacy of combining nivolumab with radiosurgery (SRS) in the treatment of patients with BM from non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC).Methods: This was a multicenter trial (NCT02978404) in which patients diagnosed with NSCLC or RCC, having ≤ 10 cc of un-irradiated BM and no prior immunotherapy were eligible. Nivolumab (240 mg or 480 mg IV) was administered for up to 2 years until progression. SRS (15–21 Gy) to all un-irradiated BM was delivered within 14 days after the first dose of nivolumab. The primary endpoint was intracranial progression free survival (iPFS).Results: Twenty-six patients (22 NSCLC and 4 RCC) were enrolled between August 2017 and January 2020. A median of 3 (1–9) BM were treated with SRS. Median follow-up was 16.0 months (0.43–25.9 months). Two patients developed nivolumab and SRS related grade 3 fatigue. One-year iPFS and OS were 45.2% (95% CI 29.3–69.6%) and 61.3% (95% CI 45.1–83.3%), respectively. Overall response (partial or complete) of SRS treated BM was attained in 14 out of the 20 patients with ≥1 evaluable follow-up MRI. Mean FACT-Br total scores were 90.2 at baseline and improved to 146.2 within 2–4 months (P = .0007).Conclusions: The adverse event profile and FACT-Br assessments suggested that SRS during nivolumab was well tolerated. Upfront SRS with the initiation of anti-PD-1 prolonged the 1-year iPFS and achieved high intracranial control. This combined approach merits validation randomized studies.

Hypoxia is a key characteristic of the tumor microenvironment, too rarely considered during drug development due to the lack of a user-friendly method to culture naturally hypoxic 3D tumor models. In this study, we used soft lithography to engineer a microfluidic platform allowing the culture of up to 240 naturally hypoxic tumor spheroids within an 80 mm by 82.5 mm chip. These jumbo spheroids on a chip are the largest to date (>750 µm), and express gold-standard hypoxic protein CAIX at their core only, a feature absent from smaller spheroids of the same cell lines. Using histopathology, we investigated response to combined radiotherapy (RT) and hypoxic prodrug Tirapazamine (TPZ) on our jumbo spheroids produced using two sarcoma cell lines (STS117 and SK-LMS-1). Our results demonstrate that TPZ preferentially targets the hypoxic core (STS117: p = 0.0009; SK-LMS-1: p = 0.0038), but the spheroids’ hypoxic core harbored as much DNA damage 24 h after irradiation as normoxic spheroid cells. These results validate our microfluidic device and jumbo spheroids as potent fundamental and pre-clinical tools for the study of hypoxia and its effects on treatment response.