An abscopal effect in a case of concomitant treatment of locally and peritoneally recurrent gastric cancer using adoptive T‐cell immunotherapy and radiotherapy

Sato, Hiro; Suzuki, Yoshiyuki; Yoshimoto, Yuya; Noda, Shin‐ei; Murata, Kazutoshi; Takakusagi, Yosuke; Okazaki, Atsushi; Sekihara, Tetsuo; Nakano, Takashi

doi:10.1002/ccr3.758

Cited by 27 publications

(23 citation statements)

References 24 publications

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“…The abscopal effect has been reported in patients treated with immune checkpoint inhibitors after radiotherapy. An abscopal effect in a patient with gastric cancer has been reported only by Sato et al [ 15 ]; it occurred following radiotherapy plus concurrent adoptive T-cell immunotherapy. Abscopal effects may be very rare in patients with gastric cancer; when such patients require postradiotherapy treatment, alternatives to nivolumab may need to be considered.…”

Section: Discussionmentioning

confidence: 99%

Hyperprogressive Disease in the Irradiation Field after a Single Dose of Nivolumab for Gastric Cancer: A Case Report

et al. 2018

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Following the ATTRACTION-2 study, nivolumab was approved for advanced gastric cancer in Japan. However, pseudoprogression and hyperprogressive disease have been reported in patients treated with immune checkpoint inhibitors. We report a patient with gastric cancer who received nivolumab after radiotherapy only to experience rapid progression within the irradiation field after the first immunotherapy session. A 66-year-old man with dysphagia visited our hospital and was diagnosed with stage IV gastroesophageal cancer (human epidermal growth factor receptor-2 score = 0). He commenced a G-SOX regimen (S-1 80 mg/m² on days 1–14 and oxaliplatin 100 mg/m² on day 1, repeated every 3 weeks) in June 2017. The dysphagia worsened despite 3 cycles of G-SOX, and computed tomography (CT) revealed constriction of the gastroesophageal junction. To ameliorate the dysphagia, palliative chemoradiotherapy (S-1 and 50.4 Gy in 28 fractions) was performed starting in August 2017. The patient’s dysphagia had not resolved after completing radiotherapy, and pain on swallowing worsened. Nivolumab (3 mg/m² every 2 weeks) was administered 7 days after the completion of radiotherapy. The patient experienced malaise and worsening dysphagia before the second cycle. CT 15 days after the first nivolumab administration revealed rapid progression in the irradiation field. His general condition rapidly deteriorated, and he died 24 days after the first administration. This episode suggests that administration of nivolumab after radiotherapy may be a risk factor for hyperprogressive disease.

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Section: Discussionmentioning

confidence: 99%

Hyperprogressive Disease in the Irradiation Field after a Single Dose of Nivolumab for Gastric Cancer: A Case Report

et al. 2018

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“…The rate of regression was reported in only two cases. Sharabi et al [20] reported the rate of regression as 95% and Sato et al as unmeasurable [21]. Most patients that were classified as PR were reported to have a minimal disease.…”

Section: Reviewmentioning

confidence: 99%

Abscopal Effect of Radiotherapy in the Immunotherapy Era: Systematic Review of Reported Cases

Dağoğlu¹,

Karaman²,

Çağlar³

et al. 2019

Cureus

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Mounting evidence suggests that radiation stimulates the immune system and this contributes to the abscopal effect, which is defined as “response at a distance from the irradiated volume.” Though identified more than 50 years ago, the abscopal effect is revisited today. One rationale is that the abscopal effect is often observed with efficient immunotherapy. Here, we give an overview of the clinical data on the abscopal effect, generated by a combination of immunotherapy and radiotherapy (RT). Only papers that included RT in combination with immunotherapy were evaluated according to four main categories including RT parameters, sequencing of therapies, the definition of the abscopal effect, and patient selection. Twenty-four cases in 15 reports were reviewed. The results varied. Patient ages ranged from 24 to 74. RT dose (median total dose 18-58 Gy) varied. Biologically effective dose (BED) 10 was calculated to be a median 49.65 Gy (28-151 Gy). The time to a documented abscopal response ranged from less than a month to 12 months. The large variation concerning fractionation and sequencing of therapies indicates that these conflicting points need to be resolved, to generate for the abscopal effect to be clinically significant.

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“…More recently, Rosenberg et al found similar objective response rates with that treatment regimen in 93 patients, noting complete response rates of 12% for those given chemotherapy alone, 20% for chemotherapy plus 2-Gy total body irradiation, and 40% for those given chemotherapy plus 12 Gy [30]. In a case study of a patient with poorly differentiated adenocarcinoma (stage IIIC) that recurred after surgery who was given T-cell and DC therapy before and concurrently with RT [31], Sato et al observed signs of tumor shrinkage and improved performance status after the concurrent treatment. These results emphasize the diversity in tested combinations of T-cell therapies and RT, and suggest that the effects of these regimens depend on the type, dose and timing of RT relative to T-cell administration.…”

Section: Clinical Data Perspective and Ongoing Trialsmentioning

confidence: 88%

Radiation Therapy and Immunotherapy: What is the Optimal Timing or Sequencing?

et al. 2018

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Radiotherapy is a component of the standard of care for many patients with locally advanced nonmetastatic tumors and increasingly those with oligometastatic tumors. Despite encouraging advances in local control and progression-free and overall survival outcomes, continued manifestation of tumor progression or recurrence leaves room for improvement in therapeutic efficacy. Novel combinations of radiation with immunotherapy have shown promise in improving outcomes and reducing recurrences by overcoming tumor immune tolerance and evasion mechanisms via boosting the immune system's ability to recognize and eradicate tumor cells. In this review, we discuss preclinical and early clinical evidence that radiotherapy and immunotherapy can improve treatment outcomes for locally advanced and metastatic tumors, elucidate underlying molecular mechanisms and address strategies to optimize timing and sequencing of combination therapy for maximal synergy.

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An abscopal effect in a case of concomitant treatment of locally and peritoneally recurrent gastric cancer using adoptive T‐cell immunotherapy and radiotherapy

Cited by 27 publications

References 24 publications

Hyperprogressive Disease in the Irradiation Field after a Single Dose of Nivolumab for Gastric Cancer: A Case Report

Hyperprogressive Disease in the Irradiation Field after a Single Dose of Nivolumab for Gastric Cancer: A Case Report

Abscopal Effect of Radiotherapy in the Immunotherapy Era: Systematic Review of Reported Cases

Radiation Therapy and Immunotherapy: What is the Optimal Timing or Sequencing?

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