Bone Marrow-sparing Intensity Modulated Radiation Therapy With Concurrent Cisplatin For Stage IB-IVA Cervical Cancer: An International Multicenter Phase II Clinical Trial (INTERTECC-2)

Mell, Loren K.; Sirák, Igor; Wei, Lichun; Tarnawski, Rafał; Mahantshetty, Umesh; Yashar, Catheryn M.; McHale, Michael; Xu, Ronghui; Honerkamp‐Smith, Gordon; Carmona, Ruben; Wright, Mary E.; Williamson, Casey W.; Kašaová, Linda; Li, Nan; Kry, Stephen F.; Michalski, Jeff M.; Bosch, Walter; Straube, William L.; Schwarz, Julie K.; Lowenstein, Jessica; Jiang, Steve B; Saenz, Cheryl C.; Plaxe, Steve; Einck, John; Khorprasert, Chonlakiet; Koonings, Paul P.; Harrison, Terry A.; Shi, Mei; Mundt, Arno J.

doi:10.1016/j.ijrobp.2016.11.027

Cited by 136 publications

(137 citation statements)

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“…However, the clinical use of such a strategy has been limited, since computed tomography (CT)‐based IMRT cannot identify ABM subregions, and the large avoidance volume compromises planning goals . 18 F‐fluorodeoxyglucose positron emission tomography ( 18 F‐FDG‐PET) and single‐photon emission CT (SPECT) have been used previously to identify ABM subregions. Previous studies have suggested that technetium‐99m ( 99m Tc) sulfur colloid SPECT defines ABM subregions that can reduce the dose to these areas .…”

Section: Introductionmentioning

confidence: 99%

“…12,13 However, the clinical use of such a strategy has been limited, since computed tomography (CT)-based IMRT cannot identify ABM subregions, and the large avoidance volume compromises planning goals. 10 18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG-PET) 14 and single-photon emission CT (SPECT) 15 have been used previously to identify ABM subregions.…”

Section: Introductionmentioning

confidence: 99%

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The volume of ^99mTc sulfur colloid SPET‐defined active bone marrow can predict grade 3 or higher acute hematologic toxicity in locally advanced cervical cancer patients who receive chemoradiotherapy

et al. 2019

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BackgroundThe purpose of the current study was to evaluate whether radiation dose‐volume metrics to technetium‐99m (99mTc) sulfur colloid single‐photon emission tomography (SPET)‐defined active bone marrow (ABM) subregions can more accurately predict acute hematologic toxicity in locally advanced cervical cancer patients who receive chemoradiotherapy than conventional dosimetric parameters.Methods and materialsThirty‐nine patients with stage IB2‐III cervical cancer who underwent 99mTc sulfur colloid SPET imaging before treatment with cisplatin‐based chemoradiation between January 2017 and March 2018 were analyzed. The total bone marrow (TBM) volume was defined as the external contours of all bones within the vertebral bodies from L4 to the coccyx, the pelvic bones, and the proximal femoral heads. The ABM volume was defined by SPET as the subregion of TBM with a nuclide uptake value greater than or equal to the mean total body nuclide uptake value. Student's t test was used to test for statistical significance between TBM and ABM dose‐volume metrics. Receiver operating characteristic (ROC) curves were generated to compare the predictors of grade 3 or higher (grade 3+) hematologic toxicity.ResultsThe mean ABM‐V40 (23.22% ± 7.65%) and ABM‐V30 (45.28% ± 9.20%) were significantly lower than the mean TBM‐V40 (33.06% ± 6.72%) and TBM‐V30 (53.08% ± 7.77%), respectively (t = 5.78, P = .001) (t = 4.13, P = .001). The ABM volume (<387.5 cm3, AUC = 0.928, P = .001), ABM‐V30 (>46.5%, AUC = 0.875, P = .001), and ABM‐V40 (>23.5%, AUC = 0.858, P = .001) can predict the occurrence of grade 3+ hematologic toxicity. Among patients with an ABM volume < 387.5 cm3, 16/19 (84.2%) had grade 3+ hematologic toxicity compared to 3/20 (15%) with an ABM volume > 387.5 cm3.ConclusionsThe ABM volume (<387.5 cm3) may be a better predictor of hematologic toxicity than conventional dose‐volume metrics, but this finding needs to be further evaluated.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The volume of ^99mTc sulfur colloid SPET‐defined active bone marrow can predict grade 3 or higher acute hematologic toxicity in locally advanced cervical cancer patients who receive chemoradiotherapy

et al. 2019

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“…SBRT planning requires delivering dose from many angles, which also increases the volume of healthy marrow affected by small doses of radiation. However, some studies showed benefits in reduction of acute hematological toxicity when bone marrow-sparring IMRT techniques were applied [42]. Moreover, as described for radiobiological issue sections, irradiation of large volume of healthy marrow causes intensive compensation in non-irradiated bones, which may result in hematological toxicity that is lower than expected.…”

Section: Factors That May Have Impact On the Tolerance Of Hypofractiomentioning

confidence: 99%

“…Modern techniques of irradiation such as bone marrow-sparing IMRT or volumetric modulated arc therapy, might thus allow a better dose distribution and reduce volumes of irradiated bone marrow [42,44,45]. The question is whether the use of such approaches is justified in cases of hypofractionated radiotherapy.…”

Section: Future Perspectivesmentioning

confidence: 99%

Hematological Toxicity of Hypofractionated Radiotherapy: A Review of the Available Evidence

Spałek

2018

Oncol Res Treat

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Hypofractionated radiotherapy is commonly used to treat many cancers. The number of indications for this fractionation schedule is increasing. Knowledge of the potential hematological toxicity arising from hypofractionated irradiation is vital since many patients receive further systemic treatment. This review analyzes the available evidence on the effect of hypofractionated radiotherapy on hematological toxicity. However, radiobiological data on bone marrow responses to high doses of radiation per fraction are sparse. Additional biological effects may also play an significant role in bone marrow function and recovery after hypofractionated radiotherapy. Clinical data show a good early hematological tolerance of hypofractionated radiotherapy (both large field and for stereotactic body radiotherapy). There are, however, no data available that assess late hematological toxicity. Evidence on acute hematological toxicity after hypofractionated radiotherapy does not suggest any significant impact of altered fractionation on early treatment tolerance, although further research to assess this problem is needed. The effect of hypofractionation on late hematological tolerance is unknown because the data are still lacking.

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“…This phenomenon, termed the "abscopal effect", is due to extensive inflammation and activation of immune cells as a result of radiation [12,13]. Contrarily, radiotherapy can lead to myelosuppression that counteracts the benefit of activated immune cells [14,15]. This cross-talk between immune cells and the irradiated site has provided a rationale for combining radiotherapy with immunotherapy, including immune checkpoint inhibitors [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Microparticles from tumors exposed to radiation promote immune evasion in part by PD-L1

Timaner¹,

Kotsofruk²,

Raviv³

et al. 2019

Oncogene

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Radiotherapy induces immune-related responses in cancer patients by various mechanisms. Here, we investigate the immunomodulatory role of tumor-derived microparticles (TMPs)-extracellular vesicles shed from tumor cells-following radiotherapy. We demonstrate that breast carcinoma cells exposed to radiation shed TMPs containing elevated levels of immune-modulating proteins, one of which is programmed death-ligand 1 (PD-L1). These TMPs inhibit cytotoxic T lymphocyte (CTL) activity both in vitro and in vivo, and thus promote tumor growth. Evidently, adoptive transfer of CTLs pre-cultured with TMPs from irradiated breast carcinoma cells increases tumor growth rates in mice recipients in comparison with control mice receiving CTLs pre-cultured with TMPs from untreated tumor cells. In addition, blocking the PD-1-PD-L1 axis, either genetically or pharmacologically, partially alleviates TMP-mediated inhibition of CTL activity, suggesting that the immunomodulatory effects of TMPs in response to radiotherapy is mediated, in part, by PD-L1. Overall, our findings provide mechanistic insights into the tumor immune surveillance state in response to radiotherapy and suggest a therapeutic synergy between radiotherapy and immune checkpoint inhibitors.

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Bone Marrow-sparing Intensity Modulated Radiation Therapy With Concurrent Cisplatin For Stage IB-IVA Cervical Cancer: An International Multicenter Phase II Clinical Trial (INTERTECC-2)

Abstract: IMRT reduces acute hematologic and GI toxicity compared with standard treatment, with promising therapeutic outcomes. Positron emission tomography IG-IMRT reduces the incidence of acute neutropenia.

Cited by 136 publications

References 34 publications

The volume of ^99mTc sulfur colloid SPET‐defined active bone marrow can predict grade 3 or higher acute hematologic toxicity in locally advanced cervical cancer patients who receive chemoradiotherapy

The volume of ^99mTc sulfur colloid SPET‐defined active bone marrow can predict grade 3 or higher acute hematologic toxicity in locally advanced cervical cancer patients who receive chemoradiotherapy

Hematological Toxicity of Hypofractionated Radiotherapy: A Review of the Available Evidence

Microparticles from tumors exposed to radiation promote immune evasion in part by PD-L1

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Bone Marrow-sparing Intensity Modulated Radiation Therapy With Concurrent Cisplatin For Stage IB-IVA Cervical Cancer: An International Multicenter Phase II Clinical Trial (INTERTECC-2)

Abstract: IMRT reduces acute hematologic and GI toxicity compared with standard treatment, with promising therapeutic outcomes. Positron emission tomography IG-IMRT reduces the incidence of acute neutropenia.

Cited by 136 publications

References 34 publications

The volume of 99mTc sulfur colloid SPET‐defined active bone marrow can predict grade 3 or higher acute hematologic toxicity in locally advanced cervical cancer patients who receive chemoradiotherapy

The volume of 99mTc sulfur colloid SPET‐defined active bone marrow can predict grade 3 or higher acute hematologic toxicity in locally advanced cervical cancer patients who receive chemoradiotherapy

Hematological Toxicity of Hypofractionated Radiotherapy: A Review of the Available Evidence

Microparticles from tumors exposed to radiation promote immune evasion in part by PD-L1

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The volume of ^99mTc sulfur colloid SPET‐defined active bone marrow can predict grade 3 or higher acute hematologic toxicity in locally advanced cervical cancer patients who receive chemoradiotherapy

The volume of ^99mTc sulfur colloid SPET‐defined active bone marrow can predict grade 3 or higher acute hematologic toxicity in locally advanced cervical cancer patients who receive chemoradiotherapy