Clinical evidence for synergy between immunotherapy and radiotherapy (<scp>SITAR</scp>)

Gill, Suki; Nowak, Anna K.; Bowyer, Samantha; Endersby, Raelene; Ebert, Martin A.; Cook, Alistair

doi:10.1111/1754-9485.13441

Cited by 10 publications

(6 citation statements)

References 101 publications

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“…Toxicity remains a critical issue in combination therapies. Given the long half-lives of ICIs, RT conducted after the last dose of ICIs is still considered as combination therapy [ 137 ]. For example, it would require 3 months for durvalumab to be cleared from the system.…”

Section: Discussionmentioning

confidence: 99%

Global research landscape and trends of cancer radiotherapy plus immunotherapy: A bibliometric analysis

Liu,

Jiang,

et al. 2024

Heliyon

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Section: Discussionmentioning

confidence: 99%

Global research landscape and trends of cancer radiotherapy plus immunotherapy: A bibliometric analysis

Liu,

Jiang,

et al. 2024

Heliyon

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“…RT is known to synergize with the antitumor effects of PD1/PD-L1 axis blockade [ 43 , 44 ]. This probably underlies some tumor responses that extend beyond the radiation field, as in the case series by Xu et al These authors reported the impressive outcomes of two patients with mMCC progressing on PD-1 inhibitor therapy and then treated with 8 Gy-single-fraction palliative radiotherapy to some portion of the tumor masses: surprisingly, both patients rapidly experienced a marked reduction until disappearance not only of the irradiated tumor portion, but also of the distant out-of-field tumor sites [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Introducing Radiotherapy in Metastatic Merkel Cell Carcinoma Patients with Limited Progression on Avelumab: An Effective Step against Primary and Secondary Immune Resistance?

Ferini¹,

Zagardo²,

Critelli

et al. 2023

JPM

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Purpose: To investigate the ability of radiotherapy (RT) to prolong progression-free survival (PFS) and to report treatment-related toxicities among oligoprogressive metastatic Merkel cell carcinoma (mMCC) patients on avelumab. Methods: We retrospectively collected clinical data on mMCC patients who underwent radiotherapy for limited progression on avelumab. Patients were categorized as primary or secondary immune refractory depending on the time of onset of resistance to immunotherapy (at the first or subsequent follow-up visits after avelumab initiation). Pre- and post-RT PFS were calculated. Overall survival (OS) from the first progression treated with RT was also reported. Radiological responses and toxicities were evaluated according to the irRECIST criteria and RTOG scoring system, respectively. Results: Eight patients, including five females, with a median age of 75 years, met our inclusion criteria. The median gross tumor and clinical target volumes at first progression on avelumab were 29.85 cc and 236.7 cc, respectively. The treatment sites included lymph node, skin, brain, and spine metastases. Four patients received more than one course of RT. Most patients were treated with palliative radiation doses (mainly 30 Gy in 3 Gy/day fractions). Two patients were treated with stereotactic RT. Five/eight patients were primary immune refractory. The objective response rate at the first post-RT assessment was 75%, whereas no local failure was reported. The median pre-RT PFS was 3 months. The pre-RT PFS was 37.5% at 6 months and 12.5% at 1 year. The median post-RT PFS was not reached. The post-RT PFS was 60% at 6 months and 1 year. The post-RT OS was 85.7% at 1 year and 64.3% at 2 years. No relevant treatment-related toxicity was observed. After a median follow-up of 18.5 months, 6/8 patients are still alive and continuing on avelumab therapy. Conclusions: Adding radiotherapy to mMCC patients with limited progression on avelumab seems to be safe and effective in prolonging the successful use of immunotherapy, regardless of the type of immune refractoriness.

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“… 17 18 Although radiotherapy can enhance antitumour effects, its potential immunosuppressive effects can also restrain antitumour efficacy, including the upregulation of coinhibitory ligands such as PD-L1. 19 20 Combining radiotherapy with immune checkpoint blockade can overcome these immunosuppressive mechanisms and augment antitumour immunity.…”

Section: Discussionmentioning

confidence: 99%

“…The antitumour effect of radiation can be attributed to the induction of tumour cell death through DNA damage, but radiotherapy also has immunomodulatory effects and can stimulate the immune response through various mechanisms 17 18. Although radiotherapy can enhance antitumour effects, its potential immunosuppressive effects can also restrain antitumour efficacy, including the upregulation of coinhibitory ligands such as PD-L1 19 20. Combining radiotherapy with immune checkpoint blockade can overcome these immunosuppressive mechanisms and augment antitumour immunity.…”

Section: Discussionmentioning

confidence: 99%

Protocol of notable-HCC: a phase Ib study of neoadjuvant tislelizumab with stereotactic body radiotherapy in patients with resectable hepatocellular carcinoma

et al. 2022

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Introduction Liver resection is the mainstay of curative-intent treatment for hepatocellular carcinoma (HCC), but the postoperative 5-year recurrence rate reaches 70%, and there are no adjuvant or neoadjuvant therapies recommended by major HCC guidelines that can reduce the risk of recurrence. In the recent decade, significant progress has been achieved in the systemic treatment of HCC, mainly from immune checkpoint inhibitors (ICIs) and targeted therapy. In other malignancies, ICIs in the neoadjuvant setting have shown better outcomes than in the adjuvant setting. On the other hand, the addition of radiation to ICIs incrementally improves the systemic response to ICIs. Neoadjuvant therapy of ICIs plus stereotactic body radiotherapy (SBRT) has shown promising results in several types of solid tumours but not HCC. Methods and analysis Here, we describe a phase Ib clinical trial of neoadjuvant SBRT plus PD-1 (tislelizumab) prior to hepatic resection in HCC patients. Prior to resection, eligible HCC patients will receive 8 Gy×3 fractions of SBRT together with two cycles of tislelizumab with an interval of 3 weeks. HCC resection is scheduled 4 weeks after the second dose of tislelizumab, followed by adjuvant tislelizumab for 1 year. We plan to enrol 20 participants in this trial. The primary study endpoints include the delay of surgery, tumour response and safety and tolerability of the sequential SBRT/tislelizumab. Other endpoints are the disease-free survival and overall survival rates every 3 or 6 months after the surgery. Ethics and dissemination This trial was approved by the Ethics Committee of Shandong Cancer Hospital and Institute (SDZLEC2022-021-01). The final results of this trial will be published in a peer-reviewed journal after completion. Trial registration number NCT05185531 .

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Clinical evidence for synergy between immunotherapy and radiotherapy (SITAR)

Cited by 10 publications

References 101 publications

Global research landscape and trends of cancer radiotherapy plus immunotherapy: A bibliometric analysis

Global research landscape and trends of cancer radiotherapy plus immunotherapy: A bibliometric analysis

Introducing Radiotherapy in Metastatic Merkel Cell Carcinoma Patients with Limited Progression on Avelumab: An Effective Step against Primary and Secondary Immune Resistance?

Protocol of notable-HCC: a phase Ib study of neoadjuvant tislelizumab with stereotactic body radiotherapy in patients with resectable hepatocellular carcinoma

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