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Proton therapy shows efficacy, low toxicity in large cohort of children with high-risk neuroblastoma.

Study supports expanded use of proton therapy to minimize radiation exposure to healthy, developing organs.

Researchers analyzed the largest cohort to date of pediatric patients with high-risk neuroblastoma treated with proton radiation therapy (PRT), finding both that proton therapy was effective at reducing tumors and demonstrated minimal toxicity to surrounding organs. “These data are extremely encouraging and could be a game-changer for a number of reasons,” said lead author Christine Hill-Kayser, MD, Chief of the Pediatric Radiation Oncology Service at Penn Medicine and an attending physician at CHOP. “Not only did we observe excellent outcomes and minimal side effects that validate the use of PRT in high-risk neuroblastoma patients, we answered a lingering question about proton therapy — the concern that because it is so targeted, tumors may come back. Tumors mostly did not come back — suggesting PRT is effective, less toxic and a superior choice for our young patients who must endure intense treatment modalities in an effort to cure this high-risk cancer.”

ScienceDaily. ScienceDaily, 9 April 2019 <www.sciencedaily.com/releases/2019/04/190409153631.htm>.

https://www.redjournal.org/article/S0360-3016(19)30190-7/fulltext

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Potential skin morbidity reduction with intensity-modulated proton therapy for breast cancer with nodal involvement

Abstract

Background: Different modern radiation therapy treatment solutions for breast cancer (BC) and regional nodal irradiation (RNI) have been proposed. In this study, we evaluate the potential reduction in radiation-induced skin morbidity obtained by intensity modulated proton therapy (IMPT) compared with intensity modulated photon therapy (IMXT) for left-side BC and RNI.

Material and Methods: Using CT scans from 10 left-side BC patients, treatment plans were generated using IMXT and IMPT techniques. A dose of 50 Gy (or Gy [RBE] for IMPT) was prescribed to the target volume (involved breast, the internal mammary, supraclavicular, and infraclavicular nodes). Two single filed optimization IMPT (IMPT1 and IMPT2) plans were calculated without and with skin optimization. For each technique, skin dose-metrics were extracted and normal tissue complication probability (NTCP) models from the literature were employed to estimate the risk of radiation-induced skin morbidity. NTCPs for relevant organs-at-risk (OARs) were also considered for reference. The non-parametric Anova (Friedman matched-pairs signed-rank test) was used for comparative analyses.

Results: IMPT improved target coverage and dose homogeneity even if the skin was included into optimization strategy (HIIMPT2 = 0.11 vs. HIIMXT = 0.22 and CIIMPT2 = 0.96 vs. CIIMXT = 0.82, p < .05). A significant relative skin risk reduction (RR = NTCPIMPT/NTCPIMXT) was obtained with IMPT2 including the skin in the optimization with a RR reduction ranging from 0.3 to 0.9 depending on the analyzed skin toxicity endpoint/model. Both IMPT plans attained significant OARs dose sparing compared with IMXT. As expected, the heart and lung doses were significantly reduced using IMPT. Accordingly, IMPT always provided lower NTCP values.

Conclusions: IMPT guarantees optimal target coverage, OARs sparing, and simultaneously minimizes the risk of skin morbidity. The applied model-based approach supports the potential clinical relevance of IMPT for left-side BC and RNI and might be relevant for the setup of cost-effectiveness evaluation strategies based on NTCP predictions, as well as for establishing patient selection criteria.

Francesco Fellin, Martina Iacco, Vittoria D’Avino, Francesco Tommasino, Paolo Farace, Giuseppe Palma, Manuel Conson, Irene Giacomelli, Claudio Zucchetti, Lorenzo Falcinelli, Maurizio Amichetti, Cynthia Aristei & Laura Cella(2019) Potential skin morbidity reduction with intensity-modulated proton therapy for breast cancer with nodal involvement, Acta Oncologica, DOI: 10.1080/0284186X.2019.1591638

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Are further studies needed to justify the use of proton therapy for paediatric cancers of the central nervous system? A review of current evidence

Myxuan Huynh, Loredana Gabriela Marcu, Eileen Giles, Michala Short, Donna Matthews, Eva Bezak

Abstract

Clinical implementation of proton therapy demonstrated its potential to overcome some limitations of the more traditional, photon-based radiotherapy, due to physical and radiobiological advantages of protons. However, questions concerning the long-term effects of protons on paediatric patients need outcome analysis of the reported literature in order to be answered. The current paper has analysed the available clinical trials and comparative studies (protons vs photons) for paediatric cancers of the central nervous system (CNS) analysing the reported outcomes and follow-up times in order to evaluate the safety of proton therapy for this patient group.

Based on the literature analysis, proton therapy for treatment of paediatric cancers of the CNS was found to provide survival and tumour control outcomes comparable, and frequently superior, to photon therapy. Furthermore, the use of protons was shown to decrease the incidence of severe acute and late toxicities, including reduced severity of endocrine, neurological, IQ and QoL deficits. Most commonly, the reported median follow-up time was up to 5 years. Only a few studies reported promising, longer follow-up results. Considering that these patients are likely to survive many of the malignancies reported on, the incidence of long term sequellae impacting growth, development and quality of life into adulthood, should be viewed longitudinally for completeness.

The evidence surrounding proton therapy in paediatric tumour management supports its effectiveness and potential benefits in reducing the incidence of late-onset toxicities and second malignancies. For stronger evidence, it is highly desired for future studies to improve current reporting by (1) highlighting the paediatric patient cohort’s outcome (in mixed patient groups), (2) reporting the follow-up time, (3) clearly indicating the toxicity criteria used in their evaluation, and (4) identifying the risk group. With this suggested clarity of future reporting, meaningful data to support treatment choice may then be available.

Table 1 Compilation of comparative studies (protons vs photons) for paediatric CNS tumours (treatment planning comparison studies not included).

Full article https://www.sciencedirect.com/science/article/pii/S0167814019300131

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A gala that will assist cancer patients undergoing proton therapy

The Hampton University Proton Therapy Institute is hosting this year’s Gala of Hope on Saturday, April 6th at the Hampton Roads Convention Center.

HUPTI treats the most complex cancer cases with proton therapy : Brain, Spine, Head and Neck, Lung, Breast, Abdomen, Prostate, Pediatrics, and Re-irradiation.
To purchase tickets visit www.hamptonproton.org/gala.

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Cardiotoxicity Associated with Radiation for Breast Cancer

Leonard K.L., Wazer D.E. (2019). In: Wright J. (eds) Toxicities of Radiation Treatment for Breast Cancer. Springer, Cham

“Strategies to reduce cardiac dose, including deep inspiration breath hold, prone positioning, partial breast irradiation, and proton therapy should be considered, particularly in women at high risk for cardiotoxicity. Based on available data, most current protocols recommend limiting mean cardiac dose and the dose to 5% and 10% of the cardiac volume.”

https://link.springer.com/chapter/10.1007/978-3-030-11620-0_7

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Proton Therapy Delivery and Its Clinical Application in Select Solid Tumor Malignancies

ABSTRACT

Radiation therapy is a frequently used modality for the treatment of solid cancers. Although the mechanisms of cell kill are similar for all forms of radiation, the in vivo properties of photon and proton beams differ greatly and maybe exploited to optimize clinical outcomes. In particular, proton particles lose energy in a predictable manner as they pass through the body. This property is used clinically to control the depth at which the proton beam is terminated, and to limit radiation dose beyond the target region. This strategy can allow for substantial reductions in radiation dose to normal tissues located just beyond a tumor target. However, the degradation of proton energy in the body remains highly sensitive to tissue density. As a consequence, any changes in tissue density during the course of treatment may significantly alter proton dosimetry. Such changes may occur through alterations in body weight, respiration, or bowel filling/gas, and may result in unfavorable dose deposition. In this manuscript, we provide a detailed method for the delivery of proton therapy using both passive scatter and pencil beam scanning techniques for prostate cancer. Although the described procedure directly pertains to prostate cancer patients, the method may be adapted and applied for the treatment of virtually all solid tumors. Our aim is to equip readers with a better understanding of proton therapy delivery and outcomes in order to facilitate the appropriate integration of this modality during cancer therapy.

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A Novel Prospective Study Assessing the Combination of Photodynamic Therapy and Proton Radiation Therapy: Safety and Outcomes When Treating Malignant Pleural Mesothelioma

“The combination of priming the immune system with intraoperative photodynamic therapy and then delivering proton therapy may have worked synergistically to stimulate the patient’s immune system to better fight the cancer,” Simone said. “More research on a cellular level is needed.”

Proton therapy is a unique type of radiation therapy that can more precisely target tumors while better protecting nearby normal tissue from the harmful radiation effects.

Normal tissues beyond and before the tumor cells are better spared, leaving far fewer side effects for patients, which is especially important with lung-sparing pleurectomy and decortication surgery. 

With a diffuse tumor such as pleural mesothelioma covering a large surface, Simone believes proton therapy is considerably more beneficial than traditional photon therapy, including the intensity-modulated radiation therapy that is often used. 

“Given the ability of proton therapy to better protect normal tissues, no patient in the entire cohort experienced any notable acute or late toxicities,” he said. “It seems to be a safe and highly effective option for these patients with great potential to reduce side effects, and even improve clinical outcomes.”

“The combination may have worked synergistically to better fight the cancer,” Dr. Charles Simone, senior study author, told The Mesothelioma Center at Asbestos.com. “Results were impressive…with better than expected clinical outcomes.”

https://www.researchgate.net/publication/329259834_A_Novel_Prospective_Study_Assessing_the_Combination_of_Photodynamic_Therapy_and_Proton_Radiation_Therapy_Safety_and_Outcomes_When_Treating_Malignant_Pleural_Mesothelioma

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IMPT versus VMAT for Pelvic Nodal Irradiation in Prostate Cancer: A Dosimetric Comparison

Thomas J. Whitaker, David M. Routman, Heather Schultz, William S. Harmsen, Kimberly S. Corbin, William W. Wong, and Richard Choo International Journal of Particle Therapy

In the setting of prostate and elective, pelvic nodal radiotherapy for prostate cancer, Intensity Modulated Proton Therapy (IMPT) can significantly reduce the dose to Organs At Risk (OAR) , in comparison to Volumetric-Modulated Arc Therapy (VMAT), and provide adequate target coverage.

The Clinical Target Volumes (CTV) coverage was adequate for both plans with 99% of CTVs receiving ≥ 100% of the prescription doses.

Mean doses to the bladder, rectum, large bowel, and small bowel were lower with IMPT versus VMAT. Mean femoral head dose was greater with IMPT.

The percentage of volumes of rectum receiving ≤ 47.5 Gy, large bowel receiving ≤ 27.5 Gy, small bowel receiving ≤ 30 Gy, and bladder receiving ≤ 37.5 Gy was less with IMPT versus VMAT, largely because of reduction in the low-dose “bath” associated with VMAT.

https://www.theijpt.org/doi/abs/10.14338/IJPT-18-00048.1

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Triple-Gaussian model improves proton therapy plans

Because the depth at which a proton beam is halted by tissue depends on its initial energy, intensity-modulated proton therapy (IMPT) allows the radiation field to conform closely to the 3D shape of the tumour while sparing surrounding tissue. This makes IMPT the method of choice for intricately shaped tumours in complex physiological settings. The narrow margins in these situations mean that a robust quality assurance procedure is needed so that clinicians can be confident that the planned dose is the one that is delivered to the patient. 

Simulated prostate treatment plan in the simple heterogeneous phantom. (Courtesy: J. Appl. Clin. Med. Phys. 10.1002/acm2.12535/CC BY 4.0)

(…) As the TPS and phantom are both commercially available, any clinic that uses IMPT based on pencil-beam scanning can use the procedure and the team’s phantom-specific correction table to verify their treatment plans. As long as absolute dose measurements are taken for each beam angle — to mitigate uncertainty related to measurement points and gantry rotation — the method provides an accurate, reproducible basis for quality assurance. “Our motivation was to realize equal access to high-quality spot-scanning proton therapy in Japan and all over the globe,” says Yasui.

https://physicsworld.com/a/triple-gaussian-model-improves-proton-therapy-plans /

https://aapm.onlinelibrary.wiley.com/doi/full/10.1002/acm2.12535

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‘Proton therapy increases survival rate of liver cancer patients’

Researchers at the National Cancer Center (NCC) have confirmed that proton therapy can increase the survival rate of both early and advanced liver cancer.

The team, led by Professors Kim Tae-hyun, Park Jung-won and Kim Bo-hyun, came to such conclusion after analyzing 243 patients who received proton therapy from June 2012 to April 2017.

The five-year survival rate of patients with proton therapy was 69 percent for patients with stage 1 liver cancer group and 65 percent for patients with stage 2 liver cancer. The rate was similar to that of other surgeries or high-frequency therapy, but significant for those patients who cannot receive surgery due to tumor location, size, recurrence, and accompanying disease such as old age, renal dysfunction.

The five-year survival rate was also 43 and 26 percent, respectively, for patients with stage 3 and 4 liver cancer.

The result was higher than the survival rates of other liver cancer treatments, indicating that proton therapy is effective in treating liver cancer in all stages. Also, none of the subjects had severe liver dysfunction due to proton therapy.

http://www.koreabiomed.com/news/articleView.html?idxno=5312