Carbon Ions for Hypoxic Tumors: Are We Making the Most of Them?

Sokol, Olga; Durante, Marco

doi:10.3390/cancers15184494

Cited by 18 publications

(6 citation statements)

References 154 publications

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“…On a side note, the combination of PULSAR with dose painting can play a unique role in both photon and particle therapy. One promising direction can be the use of carbon or, even better, oxygen ions to overcome hypoxia independently of dose painting ( 80 , 81 ).…”

Section: Discussionmentioning

confidence: 99%

Rethinking the potential role of dose painting in personalized ultra-fractionated stereotactic adaptive radiotherapy

Peng,

Deng,

Jiang

et al. 2024

Front. Oncol.

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Fractionated radiotherapy was established in the 1920s based upon two principles: (1) delivering daily treatments of equal quantity, unless the clinical situation requires adjustment, and (2) defining a specific treatment period to deliver a total dosage. Modern fractionated radiotherapy continues to adhere to these century-old principles, despite significant advancements in our understanding of radiobiology. At UT Southwestern, we are exploring a novel treatment approach called PULSAR (Personalized Ultra-Fractionated Stereotactic Adaptive Radiotherapy). This method involves administering tumoricidal doses in a pulse mode with extended intervals, typically spanning weeks or even a month. Extended intervals permit substantial recovery of normal tissues and afford the tumor and tumor microenvironment ample time to undergo significant changes, enabling more meaningful adaptation in response to the evolving characteristics of the tumor. The notion of dose painting in the realm of radiation therapy has long been a subject of contention. The debate primarily revolves around its clinical effectiveness and optimal methods of implementation. In this perspective, we discuss two facets concerning the potential integration of dose painting with PULSAR, along with several practical considerations. If successful, the combination of the two may not only provide another level of personal adaptation (“adaptive dose painting”), but also contribute to the establishment of a timely feedback loop throughout the treatment process. To substantiate our perspective, we conducted a fundamental modeling study focusing on PET-guided dose painting, incorporating tumor heterogeneity and tumor control probability (TCP).

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Section: Discussionmentioning

confidence: 99%

Rethinking the potential role of dose painting in personalized ultra-fractionated stereotactic adaptive radiotherapy

Peng,

Deng,

Jiang

et al. 2024

Front. Oncol.

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“…The higher proliferation rate of GTNs can lead to a disequilibrium between pro-and antiangiogenic signals, leading to the creation of oxygen-deficient regions, which can promote RT resistance by limiting the effectiveness of RT-induced damages. Hypoxia induces radioresistance [68]; triggers the migration and invasion ability of tumours [69], also through the production of circulating tumour cells (CTCs); and induces the production of hypoxia-inducible factors (HIF), such as HIF-1, which controls the expression of genes and pathways impacting metabolism, angiogenesis, and cell growth, differentiation, survival, and death [70,71].…”

Section: Discussionmentioning

confidence: 99%

“…In recent decades, several techniques have been proposed to overcome hypoxiainduced radioresistance, including the use of radiosensitizing drugs, delivering a boost of RT dosage to hypoxic areas, and the use of high-linear-energy-transfer (LET) heavy ions [68]. High LET RT, such as ions-RT, compared to traditional photon-beam-based RT, acts independently of tumour oxygenation status [15,86].…”

Section: Discussionmentioning

confidence: 99%

Radiation Therapy for Gestational Trophoblastic Neoplasia: Forward-Looking Lessons Learnt

Barcellini,

Fodor,

Charalampopoulou

et al. 2023

Cancers

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Gestational trophoblastic neoplasia (GTN) includes several rare malignant diseases occurring after pregnancy: invasive moles, choriocarcinoma, placental site trophoblastic tumours, and epithelioid trophoblastic tumours. Multidisciplinary protocols including multi-agent chemotherapy, surgery, and occasionally radiotherapy achieve good outcomes for some high-risk metastatic patients. In this narrative review of the published studies on the topic, we have tried to identify the role of radiotherapy. The available studies are mainly small, old, and retrospective, with incomplete data regarding radiotherapy protocols delivering low doses (which can make this disease appear radioresistant in some cases despite high response rates with palliative doses) to wide fields (whole-brain, whole-liver, etc.), which can increase toxicity. Studies considering modern techniques are needed to overcome these limitations and determine the full potential of radiotherapy beyond its antihemorrhagic and palliative roles.

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“…Notably, this range encompasses the energies commonly utilized in clinical carbon ion hadrontherapy, typically around 400 MeV per nucleon. The LET is generally under 10 keV/µm at the "entrance channel" but can ascend to above 80 keV/µm within the tumor core [66], offering a significant overlap with our investigative range.…”

Section: Radiolysis Of Water: Formation Of Primary Radical and Molecu...mentioning

confidence: 99%

Effect of Linear Energy Transfer on Cystamine’s Radioprotective Activity: A Study Using the Fricke Dosimeter with 6–500 MeV per Nucleon Carbon Ions—Implication for Carbon Ion Hadrontherapy

Penabeï,

Sepulveda,

Zakaria

et al. 2023

Molecules

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(1) Background: Radioprotective agents have garnered considerable interest due to their prospective applications in radiotherapy, public health medicine, and situations of large-scale accidental radiation exposure or impending radiological emergencies. Cystamine, an organic diamino–disulfide compound, is recognized for its radiation-protective and antioxidant properties. This study aims to utilize the aqueous ferrous sulfate (Fricke) dosimeter to measure the free-radical scavenging capabilities of cystamine during irradiation by fast carbon ions. This analysis spans an energy range from 6 to 500 MeV per nucleon, which correlates with “linear energy transfer” (LET) values ranging from approximately 248 keV/μm down to 9.3 keV/μm. (2) Methods: Monte Carlo track chemistry calculations were used to simulate the radiation-induced chemistry of aerated Fricke–cystamine solutions across a broad spectrum of cystamine concentrations, ranging from 10−6 to 1 M. (3) Results: In irradiated Fricke solutions containing cystamine, cystamine is observed to hinder the oxidation of Fe2+ ions, an effect triggered by oxidizing agents from the radiolysis of acidic water, resulting in reduced Fe3+ ion production. Our simulations, conducted both with and without accounting for the multiple ionization of water, confirm cystamine’s ability to capture free radicals, highlighting its strong antioxidant properties. Aligning with prior research, our simulations also indicate that the protective and antioxidant efficiency of cystamine diminishes with increasing LET of the radiation. This result can be attributed to the changes in the geometry of the track structures when transitioning from lower to higher LETs. (4) Conclusions: If we can apply these fundamental research findings to biological systems at a physiological pH, the use of cystamine alongside carbon-ion hadrontherapy could present a promising approach to further improve the therapeutic ratio in cancer treatments.

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Carbon Ions for Hypoxic Tumors: Are We Making the Most of Them?

Cited by 18 publications

References 154 publications

Rethinking the potential role of dose painting in personalized ultra-fractionated stereotactic adaptive radiotherapy

Rethinking the potential role of dose painting in personalized ultra-fractionated stereotactic adaptive radiotherapy

Radiation Therapy for Gestational Trophoblastic Neoplasia: Forward-Looking Lessons Learnt

Effect of Linear Energy Transfer on Cystamine’s Radioprotective Activity: A Study Using the Fricke Dosimeter with 6–500 MeV per Nucleon Carbon Ions—Implication for Carbon Ion Hadrontherapy

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