Successful combinations of radiotherapy and immunotherapy depend on the presence of live T cells within the tumor; however, radiotherapy is believed to damage T cells. Here, based on longitudinal in vivo imaging and functional analysis, we report that a large proportion of T cells survive clinically relevant doses of radiation and show increased motility, and higher production of interferon gamma, compared with T cells from unirradiated tumors. Irradiated intratumoral T cells can mediate tumor control without newly-infiltrating T cells. Transcriptomic analysis suggests T cell reprogramming in the tumor microenvironment and similarities with tissue-resident memory T cells, which are more radio-resistant than circulating/lymphoid tissue T cells. TGFβ is a key upstream regulator of T cell reprogramming and contributes to intratumoral Tcell radio-resistance. These findings have implications for the design of radio-immunotherapy trials in that local irradiation is not inherently immunosuppressive, and irradiation of multiple tumors might optimize systemic effects of radiotherapy.

BackgroundThere has been increased reporting of atypical meningioma (grade II) since the World Health Organization reclassification in 2000, and the use of postoperative radiation therapy (RT) in the treatment of these tumors is controversial. We evaluated patients treated at our institution to identify patient subgroups with increased risk of recurrence that may benefit from adjuvant RT.Methods and materialsWe retrospectively assessed 50 patients treated for World Health Organization grade II meningiomas between March 2000 and February 2013. Sex, race, age of diagnosis, tumor location, performance status, size of tumor, MIB-1 index, resection status, and RT were recorded. Patient follow-up, recurrence, and vital status were measured to assess 3-year overall survival (OS) and recurrence free survival (RFS).ResultsThe median follow-up was 37 months (range, 1-148). Female sex was associated with decreased RFS compared with male sex (86.1% vs 100%, P = .047). Subtotal resection demonstrated both inferior RFS (67.5% vs 96.6%, P = .025) and OS compared with gross total resection (70.0% vs 100%, P < .001). Tumors >4.5 cm had worse RFS than tumors ≤4.5 cm (85.4% vs 100%, P = .025). Patient OS was lower in tumors with an MIB-1 index >5% than ≤5% (89.7% vs 100%, P = .008). Eastern Cooperative Oncology Group 2-4 negatively impacted OS relative to patients with an Eastern Cooperative Oncology Group 0-1 (66.7% vs 100%, P < .001).ConclusionsSignificantly higher rates of recurrence occurred in female sex, subtotal resection, and tumors larger than 4.5 cm. Further studies are needed to confirm these findings and determine whether patients without any of these risk factors can undergo surgical resection without adjuvant radiation therapy.

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IntroductionDural tails are thickened contrast-enhancing portions of dura associated with some meningiomas. Prior studies have demonstrated the presence of tumor cells within the dural tail, however their inclusion in radiation treatment fields remains controversial. We evaluated the role of including the dural tail when treating a meningioma with stereotactic radiation and the impact on tumor recurrence.MethodsThis is a retrospective, single-institution, cohort study of patients with intracranial World Health Organization (WHO) grade 1 meningioma and identified dural tail who were treated with stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) from January 2012 to December 2018. SRS and FSRT subgroups were categorized based on coverage or non-coverage of the dural tail by the radiation fields, as determined independently by a radiation oncologist and a neurosurgeon. Demographics, tumor characteristics, radiation plans, and outcomes were evaluated. High grade tumors were analyzed separately.ResultsA total of 187 WHO grade 1 tumors from 177 patients were included in the study (median age: 62 years, median follow-up: 40 months, 78.1% female) with 104 receiving SRS and 83 receiving FSRT. The dural tail was covered in 141 (75.4%) of treatment plans. There was no difference in recurrence rates (RR) or time to recurrence (TTR) between non-coverage or coverage of dural tails (RR: 2.2% vs 3.5%, P = 1.0; TTR: 34 vs 36 months, P = 1.00). There was no difference in the rate of radiation side effects between dural tail coverage or non-coverage groups. These associations remained stable when SRS and FSRT subgroups were considered separately, as well as in a high grade cohort of 16 tumors.ConclusionInclusion of the dural tail in the SRS or FSRT volumes for meningioma treatment does not seem to reduce recurrence rate. Improved understanding of dural tail pathophysiology, tumor grade, tumor spread, and radiation response is needed to better predict the response of meningiomas to radiotherapy.

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