April 2020 : what did we learn ?

Last month, the impact of Covid-19 on cancer treatment has been discussed in many articles. Several more studies have also been published showing the benefits of Proton Therapy for Pediatric Ewing Sarcoma, Head & Neck, Oropharyngeal, Breast, Lung, Esophageal, and Prostate cancers, and for re-irradiation.

Read our selection.

COVID-19 : global consequences for oncology

This pandemic will undoubtedly change the way we work. But the oncology community is relentlessly devoted to the patients, and we will certainly weather this unprecedented storm !


Editorial| Volume 21, ISSUE 4, P467, April 01, 2020

COVID-19: global consequences for oncology
The Lancet Oncology



Challenges posed by COVID-19 to children with cancer

⚠️ Let’s get ready !
Let’s work all together and let’s optimize all our resources to make sure our young patients receive the right treatment at the right time !
👉 “The coming months will pose many further challenges, which might include accessibility to scarce resources, effects on drug manufacture and supply, and the effect on care of children with cancer from low-income and middle-income countries. Continued collaboration among the international pediatric oncology community is required to get through such uncertain times.”

Rishi S Kotecha
https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30205-9/fulltext



Treating childhood cancer : a necessity not a choice

“Inadequate access to care, late diagnosis, financial toxicity, and poor-quality care are ubiquitous barriers for children with cancer worldwide and have a crucial impact on survival outcomes. Owing to population growth and inequitable access to cancer care, 80% of the global cancer burden–in terms of both incidence and mortality is estimated to fall on children in low-income and middle-income countries (LMICs)—a humanitarian situation that demands immediate attention.”

Allison Landman
David Collingridge
https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30145-5/fulltext



Pediatric Ewing Sarcoma : Depending on the chest wall subregion, proton treatment has the potential to minimize pulmonary, cardiac, renal, and hepatic toxicity, as well as second malignancies.

👉 Target conformity and homogeneity indices are generally better for the IMPT plans with beam aperture.
👉 Doses to the lung, heart, and liver for all patients are substantially lower with the 3DPT and IMPT plans than those of IMRT plans.
👉 In the IMPT plans with large spot without beam aperture, some OAR doses are higher than those of 3DCPT plans. The integral dose of each photon IMRT plan ranged from 2 to 4.3 times of proton plans.
👉 Compared to IMRT, proton therapy delivers significant lower dose to almost all OARs and much lower healthy tissue integral dose. Compared to 3DCPT, IMPT with small beam spot size or using beam aperture has better dose conformity to the target.
👉 Treatment plan using the smaller beam spot with beam apertures provided the best combination of target coverage and OAR sparing.

Impact of different treatment techniques for pediatric Ewing sarcoma of the chest wall: IMRT, 3DCPT, and IMPT with/without beam aperture
Zhong Su et al.
https://aapm.onlinelibrary.wiley.com/doi/full/10.1002/acm2.12870#.XpmY6trKGJk.linkedin


For patients with HPV-positive oropharyngeal cancer, the predicted risk of secondary malignant neoplasms (SMN) is significantly reduced statistically for treatment with Intensity Modulated Proton Therapy (IMPT) compared with Intensity Modulated photon Radiation Therapy (IMRT).

👉 Although both modalities afforded good target coverage, IMPT plans were able to achieve improved healthy-tissue sparing : significant reductions in mean mandible, contralateral parotid, lung and skin organ equivalent doses with IMPT compared with IMRT plans (P < .001).
👉 This reduction in integral dose led to a predicted decrease of 436 additional cases of SMNs for every 10 000 patients/y (or 4 per 100 patients/y) for treatment with protons instead of photons

Predicted Secondary Malignancies following Proton versus Photon Radiation for Oropharyngeal Cancers – Jain et al
https://www.theijpt.org/doi/pdf/10.14338/IJPT-19-00076.1


Oropharyngeal cancer : proton therapy improves Patient-reported outcomes

👉 Intensity Modulated Proton Therapy is associated with improved Patient-reported outcomes, reduced percutaneous endoscopic gastrostomy -tube placement, hospitalization, and narcotic requirements.
👉 Mucositis, dysphagia, and pain were decreased with IMPT.
👉 Benefits were predominantly seen in patients treated definitively or with chemoradiotherapy.

Comparative analysis of acute toxicities and patient reported outcomes between intensity-modulated proton therapy (IMPT) and volumetric modulated arc therapy (VMAT) for the treatment of oropharyngeal cancer
Manzar et al.
https://www.sciencedirect.com/science/article/pii/S0167814020301195


Particle therapies, such as proton therapy or carbon ion therapy, proposed to reduce the burden of xerostomia in patients following chemoradiotherapy for HNSCC

👉 Particle therapies are especially able to reduce moderate to low dose exposure to the oral cavity (minor salivary glands), submandibular glands, and parotid glands with similar target coverage based on the physical properties of the Bragg peak energy deposition of these approaches.

Sticky stuff: xerostomia in patients undergoing head and neck radiotherapy-prevalence, prevention, and palliative care.
Snider JW 3rd, Paine CC 2nd Annals of Palliative Medicine, 25 Mar 2020 10.21037/apm.2020.02.36



Be aware of Radiation-Induced Cardiotoxicity (RIC), and support advanced delivery techniques

👉 Breast cancer
Based on available data, a clear relationship exists between whole-heart dose and risk of cardiac events following Radiotherapy for breast cancer with a significant increase in risk for left-sided breast cancer patients (…) Patients, with a particular focus on those with left-sided disease, should be evaluated for cardiac-sparing techniques, including but not limited to deep-inspiration breath hold (DIBH), gating, prone positioning, and/or proton therapy, to achieve the lowest dose possible.
👉 Thoracic Malignancies (Lung and Esophageal cancers)
Because of the anatomic proximity of these cancers to the heart, however, radiomodulatory techniques such as DIBH or gating may not be as helpful in reducing heart dose; thus, other techniques, such as proton therapy, may be needed.

Nichols et al.
Cardiotoxicity and Radiation Therapy: A Review of Clinical Impact in Breast and Thoracic Malignancies
https://appliedradiationoncology.com/articles/cardiotoxicity-and-radiation-therapy-a-review-of-clinical-impact-in-breast-and-thoracic-malignancies


For locally advanced esophageal cancer, ProtonTherapy (PBT) reduced the risk and severity of Adverse Eventss compared with IMRT while maintaining similar progression-free survival (PFS)

👉 The posterior mean total toxicity burden (TTB) was 2.3 times higher for IMRT (39.9; 95% highest posterior density interval, 26.2-54.9) than (PBT) (17.4; 10.5-25.0).
👉 The mean postoperative complications (POCs) score was 7.6 times higher for IMRT (19.1; 7.3-32.3) versus PBT (2.5; 0.3-5.2).
👉 The posterior probability that mean TTB was lower for PBT compared with IMRT was 0.9989, which exceeded the trial’s stopping boundary of 0.9942 at the 67% interim analysis.
👉 The 3-year PFS rate (50.8% v 51.2%) and 3-year overall survival rates (44.5% v 44.5%) were similar.

Randomized Phase IIB Trial of Proton Beam Therapy Versus Intensity-Modulated Radiation Therapy for Locally Advanced Esophageal Cancer
Lin SH, et al. J Clin Oncol. 2020;doi:10.1200/JCO.19.02503.



Re-irradiation with proton therapy is a safe and effective treatment in patients with recurrent glioblastoma

Proton therapy does not negatively effect on health-related quality of life (HRQOL), but rather it seems to preserve HRQOL until the time of disease progression :
👉 The treatment was associated with improvement or stability in most of the preselected HRQOL domains.
👉 Global health improved over time with a maximum difference of six points between baseline and 3-months follow-up.
👉 Social functioning and motor dysfunction improved over time with a maximum difference of eight and two points, respectively.
👉 Non-significant decrease in cognitive and emotional functioning.
👉 Fatigue remained stable during the analysis such as the other preselected domains.

Proton therapy re-irradiation preserves health-related quality of life in large recurrent glioblastoma
Scartoni et al.
https://link.springer.com/article/10.1007/s00432-020-03187-w



The high conformality and lack of exit dose with proton therapy offer significant advantages for reirradiation

👉 By decreasing dose to adjacent normal tissues, proton therapy can more safely deliver definitive instead of palliative doses of reirradiation, more safely dose escalate reirradiation treatment, and more safely allow for concurrent systemic therapy in the reirradiation setting.

Proton Reirradiation: Expert Recommendations for Reducing Toxicities and Offering New Chances of Cure in Patients With Challenging Recurrence Malignancies
Simone et al.


Rectal Hydrogel Spacer Improves Late Gastrointestinal Toxicity

👉 compared with rectal balloon immobilization, treatment with the hydrogel spacer significantly reduced the risk of clinically relevant (grade 2+), late rectal bleeding and was associated with a significantly lower decrease in patient-reported bowel quality of life
👉 “the rectal-sparing benefit of the hydrogel spacer, particularly for reducing late rectal bleeding, was even greater than expected. These findings can hold interest for urologists who counsel patients about their treatment options for localized prostate cancer,” added Dr. Ellis, professor and vice-chair of urology, University of Washington, Seattle.

Dinh TT et al.
Rectal Hydrogel Spacer Improves Late Gastrointestinal Toxicity Compared to Rectal Balloon Immobilization After Proton Beam Radiation Therapy for Localized Prostate Cancer: A Retrospective Observational Study.
https://www.ncbi.nlm.nih.gov/pubmed/32035187


Prostate cancer : Hydrogel spacer reduce the rectal dose

👉 Significant rectal dose reduction (P < 0.001) between the treatment plans on pre- and post-CT images were achieved for all modalities for D50%, D20% and D2%.
👉 In particular, the dose reduction of high-dose (D2%) ranges were : −40.61 ± 11.19 for proton therapy −32.44 ± 5.51 for CK −25.90 ± 9.89 for HT −13.63 ± 8.27 for VMAT −8.06 ± 4.19% for 3DCRT
👉 The results of this study demonstrated that all external radiotherapy modalities with hydrogel spacer could reduce the rectal dose.”

Comparison of rectal dose reduction by a hydrogel spacer among 3D conformal radiotherapy (3DCRT), volumetric-modulated arc therapy (VMAT), helical tomotherapy (HT), CyberKnife (CK) and proton therapy – Saito et al.
Journal of Radiation Research, rraa013, https://lnkd.in/dU9-Zcw

Figure : Typical dose distribution of SO(−) and SO(+) and the results of five modalities: (a) 3DCRT, (b) VMAT, (c) HT, (d) CK and (e) proton. The contour of the orange color illustrates the rectum.

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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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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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The relationship between radiation doses to coronary arteries and location of coronary stenosis requiring intervention in breast cancer survivors

Anna-Karin Wennstig, Hans Garmo, Ulf Isacsson, Giovanna Gagliardi, Niina Rintelä, Bo Lagerqvist, Lars Holmberg, Carl Blomqvist, Malin Sund and Greger Nilsson

Radiation Oncology201914:40

This study assessed the relationship between radiation doses to the coronary arteries (CAs) and location of a coronary stenosis that required intervention after three-dimensional conformal radiotherapy (3DCRT) for breast cancer (BC).

In women receiving conventional 3D Conformal RadioTherapy for Breast Cancer between 1992 and 2012, radiation doses to the Left Anterior Descending Artery (LAD) remained high and were associated with an increased requirement of coronary intervention in mid LAD. The results support that the LAD radiation dose should be considered in RT treatment planning and that the dose should be kept as low as possible.

Reducing the dose to LAD, and implementation of heart-sparing RT techniques is of importance, since minimising the dose to LAD is expected to diminish the risk of later radiation-induced stenosis.

https://ro-journal.biomedcentral.com/articles/10.1186/s13014-019-1242-z

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