Temporally-Dependent Intracranial Control of Melanoma Brain Metastasis by Stereotactic Radiation Therapy in Patients Treated With Immune Checkpoint Blockade

Jiang, Wen Qi; Rodriguez, Y.; Kim, B.Y.S.; Tang, Chad; Haydu, Lauren E.; Mahajan, Anita; Davies, Michael A.; Hwu, Patrick; Sulman, Erik P.; Brown, Paul D.; Li, J.

doi:10.1016/j.ijrobp.2015.07.137

Cited by 4 publications

(3 citation statements)

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“…Schoenfeld et al 17 also found in a small series of 16 patients that SRS before ipilimumab was associated with increased survival in comparison with SRS after ipilimumab. Jiang et al 18 subsequently reported in abstract form that in a larger cohort of 71 patients, those who received SRS within 5.5 months of their last dose of ipilimumab had significantly improved intracranial control in comparison with those who received SRS after 5.5 months; however, they did not find a difference in overall survival. Although our study was not designed to look at survival, a subanalysis of our data also suggests a trend toward increased survival with concurrent treatment, although this did not reach statistical significance.…”

Section: Discussionmentioning

confidence: 99%

Timing and type of immune checkpoint therapy affect the early radiographic response of melanoma brain metastases to stereotactic radiosurgery

Qian

Kluger

et al. 2016

Cancer

193

144

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Background Growing evidence suggests that immunotherapy and radiation therapy can be synergistic in the treatment of cancer. We sought to determine the effect of the relative timing and type of immune checkpoint therapy on response of melanoma brain metastases to treatment with stereotactic radiosurgery (SRS). Methods 75 melanoma patients with 566 brain metastases were treated with both SRS and immunotherapy between 2007 and 2015 at a single institution. Immunotherapy and radiosurgery treatment to any single lesion was considered concurrent if SRS was administered within four weeks of immunotherapy. The impact of timing and type of immunotherapy on lesional response was determined using the Wilcoxon rank sum test to compare median percent lesion volume change at 1.5 months, 3 months, and 6 months after SRS treatment, with significance determined by p=0.0167, per the Bonferroni correction for multiple comparisons. Results Concurrent use of immunotherapy and SRS resulted in significantly greater median percent reduction in lesion volume at 1.5 months (−63.1% vs −43.2%, p<0.0001), 3 months (−83.0% vs −52.8%, p<0.0001), and 6 months (−94.9% vs −66.2%, p<0.0001) compared to non-concurrent therapy. Median percent reduction in lesion volume was also significantly greater for anti-PD-1 than for anti-CTLA-4 at 1.5 months (−71.1% vs −48.2%, p<0.0001), 3 months (−89.3% vs −66.2%, p<0.0001), and 6 months (−95.1% vs −75.9%, p=0.0004). Conclusions Administration of immunotherapy within four weeks of SRS results in improved lesional response of melanoma brain metastases compared to treatment separated by greater than four weeks. Anti-PD-1 therapy also results in greater lesional response than anti-CTLA-4 after SRS.

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Section: Discussionmentioning

confidence: 99%

Timing and type of immune checkpoint therapy affect the early radiographic response of melanoma brain metastases to stereotactic radiosurgery

Qian

Kluger

et al. 2016

Cancer

193

144

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“…For example, Jiang et al reported that outcomes were best for patients with brain metastases who received SRS and ipilimumab when the SRS was given within 5.5 months of the last ipilimumab treatment. 35 In the setting of advanced cervical cancer, patients with lymph node-positive cervical cancer were treated on a recent phase 1 study of ipilimumab sequentially after standard-of-care chemoradiation therapy and demonstrated a 1-year disease-free survival rate of 74%, indicating possible activity of a consolidative strategy in a population with a poor prognosis. That study also illustrated an increase in PD-1 expression during chemoradiation therapy that was sustained with the administration of ipilimumab.…”

Section: Clinical Datamentioning

confidence: 99%

Immunotherapy and radiation therapy sequencing: State of the data on timing, efficacy, and safety

Williamson

Sherer

Zamarin

et al. 2021

Cancer

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Radiation therapy exerts a tumoricidal local effect as well as both local and systemic immunomodulation. Immune checkpoint blockade has become a widely used treatment modality across cancer types with a rapidly growing list of agents and US Food and Drug Administration-approved indications. Moreover, there may be synergy between radiation therapy and immune checkpoint blockade. Various strategies have been used, but the optimal sequencing of these therapies is unclear. In this review, the authors discuss the major mechanisms of available immune checkpoint inhibitors and explore the available preclinical and clinical evidence regarding treatment sequencing. They also review safety considerations and conclude with possible future directions.

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“…Notably, however, the patients who received ipilimumab after SRS in this study had initially responded poorly to the SRS, and the ipilimumab had been given >2 months after the SRS. Jiang et al reported early findings from a retrospective comparison of patients given SRS either within 5.5 months or ≥5.5 months after ipilimumab for brain metastases; that comparison showed that giving SRS closer to the last dose of ipilimumab led to the best intracranial control rates and that better control also correlated with higher absolute lymphocyte counts [72]. Schoenfeld et al also reported a case review of 16 patients who had received whole-brain RT + SRS with ipilimumab for brain metastatic disease [73].…”

Section: Clinical Data Perspectives and Ongoing Trialsmentioning

confidence: 99%

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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Temporally-Dependent Intracranial Control of Melanoma Brain Metastasis by Stereotactic Radiation Therapy in Patients Treated With Immune Checkpoint Blockade

Cited by 4 publications

References 0 publications

Timing and type of immune checkpoint therapy affect the early radiographic response of melanoma brain metastases to stereotactic radiosurgery

Timing and type of immune checkpoint therapy affect the early radiographic response of melanoma brain metastases to stereotactic radiosurgery

Immunotherapy and radiation therapy sequencing: State of the data on timing, efficacy, and safety

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

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