Hyperthermia with photon radiotherapy is thermoradiobiologically analogous to neutrons for tumors without enhanced normal tissue toxicity

Datta, Niloy Ranjan; Bodis, Stephan

doi:10.1080/02656736.2019.1679895

Cited by 7 publications

(7 citation statements)

References 45 publications

(125 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These magnetic nanoparticles in the presence of alternating magnetic field could deliver local hyperthermia and with additional payloads could act as "nanobullets." The figure has been reproduced and modified with permission from Datta et al (212,213).…”

Section: Strengths: Online and Non-invasive Thermometry Treatment Planning And Controlmentioning

confidence: 99%

Integrating Loco-Regional Hyperthermia Into the Current Oncology Practice: SWOT and TOWS Analyses

et al. 2020

Self Cite

View full text Add to dashboard Cite

Moderate hyperthermia at temperatures between 40 and 44 • C is a multifaceted therapeutic modality. It is a potent radiosensitizer, interacts favorably with a host of chemotherapeutic agents, and, in combination with radiotherapy, enforces immunomodulation akin to "in situ tumor vaccination." By sensitizing hypoxic tumor cells and inhibiting repair of radiotherapy-induced DNA damage, the properties of hyperthermia delivered together with photons might provide a tumor-selective therapeutic advantage analogous to high linear energy transfer (LET) neutrons, but with less normal tissue toxicity. Furthermore, the high LET attributes of hyperthermia thermoradiobiologically are likely to enhance low LET protons; thus, proton thermoradiotherapy would mimic 12 C ion therapy. Hyperthermia with radiotherapy and/or chemotherapy substantially improves therapeutic outcomes without enhancing normal tissue morbidities, yielding level I evidence reported in several randomized clinical trials, systematic reviews, and meta-analyses for various tumor sites. Technological advancements in hyperthermia delivery, advancements in hyperthermia treatment planning, online invasive and non-invasive MR-guided thermometry, and adherence to quality assurance guidelines have ensured safe and effective delivery of hyperthermia to the target region. Novel biological modeling permits integration of hyperthermia and radiotherapy treatment plans. Further, hyperthermia along with immune checkpoint inhibitors and DNA damage repair inhibitors could further augment the therapeutic efficacy resulting in synthetic lethality. Additionally, hyperthermia induced by magnetic nanoparticles coupled to selective payloads, namely, tumor-specific radiotheranostics (for both tumor imaging and radionuclide therapy), chemotherapeutic drugs, immunotherapeutic agents, and gene silencing, could provide a comprehensive tumor-specific theranostic modality akin to "magic (nano)bullets." To get a realistic overview of the strength (S), weakness (W), opportunities (O), and threats (T) of hyperthermia, a SWOT analysis has been undertaken. Additionally, a TOWS analysis Datta et al.Hyperthermia: SWOT and TOWS Analyses categorizes future strategies to facilitate further integration of hyperthermia with the current treatment modalities. These could gainfully accomplish a safe, versatile, and cost-effective enhancement of the existing therapeutic armamentarium to improve outcomes in clinical oncology.

show abstract

Section: Strengths: Online and Non-invasive Thermometry Treatment Planning And Controlmentioning

confidence: 99%

Integrating Loco-Regional Hyperthermia Into the Current Oncology Practice: SWOT and TOWS Analyses

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Radiotherapy (RT) is supposedly a curative treatment modality, but the radiation dose required to eradicate all cancer cell subpopulations in a tumour can often not be applied due to severe acute or long-term side effects, which include radiation-induced tissue fibrosis and second malignancies 11 . Hyperthermia is known to be one of the most potent radiosensitisers [12][13][14][15][16] , meaning that less radiation is required to achieve the same local tumour cell kill, thereby reducing the adverse effects of radiation in the adjacent normal tissues, e.g. [17][18][19][20][21] .…”

mentioning

confidence: 99%

Mathematical model for the thermal enhancement of radiation response: thermodynamic approach

Mendoza

Michlíková

Berger

et al. 2021

Sci Rep

View full text Add to dashboard Cite

Radiotherapy can effectively kill malignant cells, but the doses required to cure cancer patients may inflict severe collateral damage to adjacent healthy tissues. Recent technological advances in the clinical application has revitalized hyperthermia treatment (HT) as an option to improve radiotherapy (RT) outcomes. Understanding the synergistic effect of simultaneous thermoradiotherapy via mathematical modelling is essential for treatment planning. We here propose a theoretical model in which the thermal enhancement ratio (TER) relates to the cell fraction being radiosensitised by the infliction of sublethal damage through HT. Further damage finally kills the cell or abrogates its proliferative capacity in a non-reversible process. We suggest the TER to be proportional to the energy invested in the sensitisation, which is modelled as a simple rate process. Assuming protein denaturation as the main driver of HT-induced sublethal damage and considering the temperature dependence of the heat capacity of cellular proteins, the sensitisation rates were found to depend exponentially on temperature; in agreement with previous empirical observations. Our findings point towards an improved definition of thermal dose in concordance with the thermodynamics of protein denaturation. Our predictions well reproduce experimental in vitro and in vivo data, explaining the thermal modulation of cellular radioresponse for simultaneous thermoradiotherapy.

show abstract

“…A number of phase III randomized trials, pairwise meta-analyses and network meta-analyses have shown the efficacy of HT in a wide range of malignancies [7,8,20,[32][33][34][35][36]. Thermoradiobiologically, HT with photons is analogous to that of neutrons but devoid of any added acute or late morbidity while with protons it mimics 12 C beam therapy [37][38][39][40]. In phase III randomized study, HT with CT has improved survival outcomes in soft tissue sarcoma [41].…”

Section: Discussionmentioning

confidence: 99%

Quantification of thermal dose in moderate clinical hyperthermia with radiotherapy: a relook using temperature–time area under the curve (AUC)

Datta

Marder

Datta

et al. 2021

International Journal of Hyperthermia

Self Cite

View full text Add to dashboard Cite

Background: Thermal dose in clinical hyperthermia reported as cumulative equivalent minutes (CEM) at 43 C (CEM43) and its variants are based on direct thermal cytotoxicity assuming Arrhenius 'break' at 43 C. An alternative method centered on the actual time-temperature plot during each hyperthermia session and its prognostic feasibility is explored. Methods and materials: Patients with bladder cancer treated with weekly deep hyperthermia followed by radiotherapy were evaluated. From intravesical temperature (T) recordings obtained every 10 secs, the area under the curve (AUC) was computed for each session for T > 37 C (AUC > 37 C) and T ! 39 C (AUC ! 39 C). These along with CEM43, CEM43(>37 C), CEM43(!39 C), T mean , T min and T max were evaluated for bladder tumor control. Results: Seventy-four hyperthermia sessions were delivered in 18 patients (median: 4 sessions/patient). Two patients failed in the bladder. For both individual and summated hyperthermia sessions, the T mean , CEM43, CEM43(>37 C), CEM43(!39 C), AUC > 37 C and AUC ! 39 C were significantly lower in patients who had a local relapse. Individual AUC ! 39 C for patients with/without local bladder failure were 105.9 ± 58.3 C-min and 177.9 ± 58.0 C-min, respectively (p ¼ 0.01). Corresponding summated AUC ! 39 C were 423.7 ± 27.8 C-min vs. 734.1 ± 194.6 C-min (p < 0.001), respectively. The median AUC ! 39 C for each hyperthermia session in patients with bladder tumor control was 190 C-min. Conclusion: AUC ! 39 C for each hyperthermia session represents the cumulative time-temperature distribution at clinically defined moderate hyperthermia in the range of 39 C to 45 C. It is a simple, mathematically computable parameter without any prior assumptions and appears to predict treatment outcome as evident from this study. However, its predictive ability as a thermal dose parameter merits further evaluation in a larger patient cohort.

show abstract

Hyperthermia with photon radiotherapy is thermoradiobiologically analogous to neutrons for tumors without enhanced normal tissue toxicity

Cited by 7 publications

References 45 publications

Integrating Loco-Regional Hyperthermia Into the Current Oncology Practice: SWOT and TOWS Analyses

Integrating Loco-Regional Hyperthermia Into the Current Oncology Practice: SWOT and TOWS Analyses

Mathematical model for the thermal enhancement of radiation response: thermodynamic approach

Quantification of thermal dose in moderate clinical hyperthermia with radiotherapy: a relook using temperature–time area under the curve (AUC)

Contact Info

Product

Resources

About