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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Takeaway from BJR Proton Therapy special feature

Targeting cancer stem cells: protons versus photons – Dini et al.

👉 preclinical data suggest that protons and photons differ in their biological effects on cancer stem cells, with protons offering potential advantages, although the heterogeneity of cancer stem cells and the different proton irradiation modalities make the comparison of the results not so easy. 

Is there a role for arcing techniques in proton therapy ? – Carabe-Fernandez et al.

👉 although Proton Arc Therapy (PAT) may not produce better physical dose distributions than intensity modulated proton therapy, the radiobiological considerations associated with particular PAT techniques could offer the possibility of an increased therapeutic index.

Proton minibeams—a springboard for physics, biology and clinical creativity – Avraham Dilmanian et al.

👉 Proton minibeam therapy (PMBT) is a form of spatially fractionated radiotherapy wherein broad beam radiation is replaced with segmented minibeams—either parallel, planar minibeam arrays generated by a multislit collimator or scanned pencil beams that converge laterally at depth to create a uniform dose layer at the tumor. By doing so, the spatial pattern of entrance dose is considerably modified while still maintaining tumor dose and efficacy. Recent studies using computational modeling, phantom experiments, in vitro and in vivo preclinical models, and early clinical feasibility assessments suggest that unique physical and biological attributes of PMBT can be exploited for future clinical benefit

FLASH and minibeams in radiation therapy: the effect of microstructures on time and space and their potential application to protontherapy – Mazal et al.

👉 the combination of FLASH and minibeams using proton beams, in spite of their complexity, may help to optimize the benefits of several or all the reviewed aspects, through the following concepts:
(1)  the intrinsic advantages of protons to reduce the integral mid and low doses, will be volumetrically combined in synergy with the FLASH and minibeam effects as a whole;
(2)  to reduce mid and high equivalent doses in critical organs around the tumour volume using the FLASH effect with high dose rates achievable with proton beams, both with passive or pencil beam approaches;
(3) to reduce healthy tissue complications by the minibeams space modulation in every beam path, where protons can be focalized with a steep penumbra and hence a high peak to valley ratio;
(4) to deliver an homogeneous dose to the target at any depth using the multiple scattering of proton minibeams in depth, and/or with multiple fields, or even setting a controlled inhomogeneous “vertex” doses escalation approach, optimizing intensity modulated proton therapy with robust solutions;
(5) to modify present approaches of immunological responses by the combination of concentration of lattice doses in very short time with a slight increase in LET, and the microstructure in time and space of both effects and
(6) to deliver single or hypofractionated treatments in very short time per fraction, facilitating the treatment of moving organs, specially when using pencil beam approaches and the associated risk of interplay effects, as well as the optimal use of minibeams with minimal risk of movement during the fraction.
Proton beams have in consequence one of the highest potentials to optimize the use of FLASH and Minibeams effects in radiation therapy, individually or in a synergistic combination.

Re-irradiation with protons or heavy ions with focus on head and neck, skull base and brain malignancies – Seidensaal et al.

👉 Re-irradiation can offer a potentially curative solution in case of progression after initial therapy; however, a second course of radiotherapy can be associated with an increased risk of severe side-effects. Particle therapy with protons and especially carbon ions spares surrounding tissue better than most photon techniques, thus it is of high potential for re-irradiation. Irradiation of tumors of the brain, head and neck and skull base involves several delicate risk organs, e.g. optic system, brainstem, salivary gland or swallowing muscles. Adequate local control rates with tolerable side-effects have been described for several tumors of these locations as meningioma, adenoid cystic carcinoma, chordoma or chondrosarcoma and head and neck tumors.

Reduced radiation-induced toxicity by using proton therapy for the treatment of oropharyngeal cancer – Meijer et al.

👉 proton therapy results in lower dose levels in multiple organs at risk, which translates into reduced acute toxicity (i.e. up to 3 months after radiotherapy), while preserving tumour control. Next to reducing mucositis, tube feeding, xerostomia and distortion of the sense of taste, protons can improve general well-being by decreasing fatigue and nausea. Proton therapy results in decreased rates of tube feeding dependency and severe weight loss up to 1 year after radiotherapy, and may decrease the risk of radionecrosis of the mandible.

Photons or protons for reirradiation in (non-)small cell lung cancer: Results of the multicentric ROCOCO in silico study – Troost et al.

👉 IMPT was able to statistically significantly decrease the radiation doses to the OARs. IMPT was superior in achieving the highest tumour dose while also decreasing the dose to the organs at risk.

Paediatric proton therapy – Thomas et al.

👉 Along with high cure rates, the rate of (late) toxicities is reduced using this radiotherapy modality


Articles cited above and many more are available in Proton therapy special feature, The British Journal of Radiology 2020 93:1107 

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Daily anesthesia and Proton Therapy

Proton Therapy is unique in its accuracy and in its heightened ability to avoid damage to healthy cells or tissues during treatment. Because Proton Therapy precisely targets the tumor, it requires exact patients positioning. While the procedure itself is painless, the immobilization constraints may necessitate the provision of sedation or anesthesia for children, during simulation and treatment, to ensure patient safety.

This procedure might sound frightening, but watch Zahra, she has given us another great lesson here !

Having already received 20 fractions, she is still happy to come every day to the Hampton Proton Therapy Centre to get her treatment.

Zahra is a shy 7-year old girl diagnosed with medulloblastoma on September 2019. Her presenting symptoms included ataxia, nystagmus, and headaches. She quickly underwent a surgery to remove most of her brain tumor, and a shunt was placed during the resection due to papilledema and evidence of hydrocephalus at diagnosis.

On post-operative imaging, a 2 cm residual disease was identified. Her mother noted some right-sided motor weakness post-operatively and posterior fossa syndrome. By November 2019, Zahra started weekly chemotherapy and had been referred to SAH Care for Proton Therapy.

Zahra traveled to the US with her parents and has been treated by our Dr Allan Thornton at the Hampton University Proton Therapy Institute. She came to the centre every day from Monday to Friday for 1 hour to receive her recommended total of 33 fractions. And every day she received a light anesthesia to ensure she didn’t move during the treatment.

Zahra had elected Walter, our Anesthesia Nurse, as her new best friend.  Every day, they were walking together along the corridor to fetch  Zahra’s anesthesia stretcher. Singing, playing, and laughing.

Zahra successfully completed her treatment in Hampton and went back home. Approximately 2 months after completion of proton therapy, all symptoms are currently resolved per Zahra’s mother.

When we saw her in February 2020, Zahra appeared to be recovering well and no longer complained of any symptom. She plays well and seems to have few current limitations to her activity.

Thank you Zahra for this lesson in courage and for your trust and confidence in our team !

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Takeaway from Multidisciplinary 2020 Head and Neck Cancers Symposium

A dosimetric comparison of proton versus photon irradiation for pediatric glomus tumor – Vidal et al.

👉 Most notable are the lower doses to ipsilateral (left) cochlea, right-sided structures, and expanded cord with the proton plan. The mean oral cavity dose was also significantly lower. 
Dosimetric superiority of protons in the skull base region is largely due to the absence of dose deposition distal to the target, or “exit dose”. This phenomenon is explained by the distinctive Bragg Peak that protons have which allows for a rapid fall-off of the irradiation dose beyond the target. Contralateral structures were significantly spared with the proton plan. As previously established, proton beam therapy remains the therapy of choice for pediatric patients given their long term survival and concerns for secondary malignancy, as well as lower doses to most if not all normal structures of interest.

Long-Term Update of Proton Beam Re-Irradiation for Recurrent Head and Neck Cancer – Lee et al.

👉 Proton Therapy re-irradiation of the head and neck provides effective tumor control with acceptable acute and late toxicity profiles, likely secondary to the decreased dose to surrounding normal, albeit previously irradiated tissue.

Proton Therapy for Non-Skull Base Head and Neck Adenoid Cystic Carcinoma – Lee et al.

👉 Proton Therapy is a feasible option for ACC for the non-skull based head and neck in the definitive and postoperative setting, offering low rates of acute and late toxicities. Patients with metastatic disease also had acceptable outcomes and local treatment was well tolerated.

Improved Outcomes by proton beam radiation for nasal cavity and paranasal sinus malignances – Fan et al.

👉 Proton Therapy offers durable local control and survival in patients with nasal cavity and paranasal sinus malignancy. Even patients with recurrent tumor or with prior radiation history could achieve encouraging outcomes.

Chemosensory Outcomes in Nasopharyngeal Cancer Patients Treated with Proton Beam Therapy: A Prospective Longitudinal Study – Slater et al.

👉 with Proton Therapy the long-term chemosensory outcomes are preserved.

Proton Therapy for Nasopharyngeal Cancer: A Matched Case-control Study of Intensity-Modulated Proton Therapy and Intensity-Modulated Photon Therapy – Li et al.

👉 IMPT showed dosimetry advantages over  IMRT and lower rates of acute toxicities while both had comparable  treatment outcomes.

Outcomes following Proton Therapy for Squamous Cell Carcinoma of the Larynx – Ausat et al.

👉 Proton Therapy for SCC of the larynx demonstrates a high rate of overall survival, local-regional control, and disease-free survival with low toxicity profile.

Outcomes of Major Salivary Gland Tumors Treated with Proton Beam Radiation Therapy – Zakeri et al.

👉 rates of locoregional control were high and treatment was well tolerated.

Intensity Modulated Proton Therapy (IMPT) to the Parotid
Gland: A Seven-Year Experience – Hanania et al.

👉 IMPT for treatment 724 of the parotid gland manifests in low rates of acute and chronic toxicity 725 while maintaining dosimetric coverage and high rates of biological control. 726 Skin V30 may predict for radiation dermatitis.

Redefine End-of-range RBE of Protons Based on Long-term Clinical Outcome – Zhan et al.

👉 RBE in brain is 1.18

Abstracts published in International Journal of Radiation Oncology • Biology • Physics, Volume 106, Issue 5, April 1, 2020

https://www.redjournal.org/issue/S0360-3016(20)X0004-6


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This is SAH Care

We could tell you the story of Zahra, a 6-year old girl from Bahrain diagnosed with a medulloblastoma.

We could detail her pathology and the treatment plan agreed with her local medical team.

We could report the heartbreaking words from her family.

We could depict the efforts by the Ministry of Health and US Embassy Teams to have her traveling as soon as possible.

We could relate her journey to Hampton.

We could talk about the exams and procedures she underwent.

We could narrate how we’ve struggled to get her chemotherapy in short-supply.

We could elaborate on the benefits of Proton Therapy over other treatment modalities in her case.

But we can’t describe the love we share with our patients.

Zahra has elected Walter, our Anesthesia Nurse, as her new best friend.  They’re walking together along the corridor to fetch  Zahra’s anesthesia stretcher. They come from different countries, 50 years separate them, they don’t speak a common language, and yet they truly love each other.

This is SAH Care !

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Proton therapy: the current status of the clinical evidences – by Dongryul Oh

Precision and Future Medicine 2019

Proton Therapy Clinical Evidences – Dongryul Oh

The dosimetric advantages of proton therapy—compared with photon therapy—have been clearly defined in many comparison studies involving various tumor sites. There are now accumulating clinical data demonstrating that this dosimetric advantage can lead to better outcomes such as reduced RT toxicity and improved treatment outcomes. 

Pediatric Tumors

RT has an important role in treating pediatric tumors including central nervous system (CNS) tumors, extra-cranial sarcomas, neuroblastoma, and hematopoietic tumors. Long-term toxicities, including secondary malignancies, neurocognitive dysfunctions, growth and musculoskeletal problems, and cardiac problems, are major concerns in pediatric patients who undergo RT. There have been many efforts to reduce the RT dose and volume to avoid these RT-related toxicities.

Proton therapy is one of the best options to reduce unnecessary irradiation dose and volume in pediatric patients.

More than 30 pediatric tumor types were treated, mainly with curative intent: 48% were CNS, 25% extra-cranial sarcomas, 7% neuroblastoma, and 5% hematopoietic tumors

Head and Neck Tumors

Retrospective data have demonstrated better local control (LC) and overall survival (OS) with proton therapy than with photon therapy including IMRT and stereotactic body radiation therapy (SBRT).

Proton therapy has also demonstrated better survival rates in nasal cavity and paranasal sinus tumors.

In oropharyngeal cancers, proton therapy can reduce toxicity to normal tissues.

Proton therapy can also reduce toxicities in unilateral irradiation, such as in cases involving major salivary gland tumor and oral cavity cancers, because the exit dose of the proton beam is essentially negligible

CNS tumors

Cognitive impairment has been one of major concerns following RT for CNS tumors. Proton therapy has a potential benefit to reduce the irradiated dose to normal brain tissue to prevent cognitive dysfunction. In addition, a dose escalation could be possible in radioresistant brain tumors such as high-grade gliomas.

Gastrointestinal tumors

Proton therapy can spare the surrounding normal tissues when it is used to treat gastrointestinal tumors. In the management of hepatocellular carcinoma (HCC), it is very important to spare liver function. Because the liver is an organ with parallel functional subunit in the model of radiation response of normal tissues, liver toxicity is more sensitive to irradiated volume. Proton therapy has a major advantage in reducing the irradiated volume of remnant liver when irradiating the tumor. In many retrospective trials, proton therapy resulted in favorable outcomes.

Re-irradiation

Proton therapy has the advantage of irradiating the target while reducing the dose to the surrounding normal tissues; thus, it has a potential benefit in re-irradiation. Many retrospective studies investigating re-irradiation in various tumor sites have been reported.

Non-Small Cell Lung Cancer

Low-dose shower is a major risk for radiation pneumonitis (RP) when treating non-small cell lung cancer (NSCLC) with photon therapy. If the lateral beam placement is avoided to reduce the lung dose, the irradiated dose to heart is consequently increased and results in increased cardiac death in long-term follow-up. In many dosimetric studies, proton therapy demonstrated advantages in lung and heart dose compared with photon therapy. Several clinical studies have reported treatment outcomes and toxicities of proton therapy in early-stage disease, locally advanced disease, re-irradiation, and in postoperative settings 

Indications for Proton Therapy

American Society for Radiation Oncology (ASTRO)  has updated the recommendations for insurance coverage. The ASTRO recommendation is based on four selection criteria:

  1. a decrease in dose inhomogeneity in a large treatment volume is required to avoid an excessive dose “hotspot” within the treated volume to lessen the risk for excessive early or late normal tissue toxicity;
  2. the target volume is in close proximity to ≥1 critical structure(s), and a steep dose gradient outside the target must be achieved to avoid exceeding the tolerance dose to the critical structure(s);
  3. a photon-based technique would increase the probability of clinically meaningful normal tissue toxicity by exceeding an integral dose-based metric associated with toxicity;
  4. and, finally, the same or an immediately adjacent area has been previously irradiated, and the dose distribution in the patient must be carefully modelled to avoid exceeding the cumulative tolerance dose to nearby normal tissues.

Based on the above medical necessity requirements and published clinical data, group 1, which is recommended coverage is listed as follows:

  • ocular tumors, including intraocular melanomas;
  • skull base tumors, primary or metastatic tumors of the spine, where spinal cord tolerance may be exceeded with conventional treatment or where the spinal cord has previously been irradiated;
  • hepatocellular cancer;
  • pediatric tumors;
  • patients with genetic syndromes making total volume of radiation minimization crucial;
  • malignant and benign primary CNS tumors;
  • advanced and/or unresectable H&N cancers;
  • the paranasal sinuses and other accessory sinuses cancers;
  • non-metastatic retroperitoneal sarcomas;
  • and cases requiring re-irradiation.

Read the full study on Precision and Future Medicine 2019

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Advantage of proton-radiotherapy for pediatric patients and adolescents with Hodgkin’s disease

a Areas in which the VMAT / IMRT plans will deliver more dose to organs at risk or the body compartment. b Areas in which the proton plan delivers more dose to organs at risk or the body compartment compared to the VMAT / IMRT plant

“Proton therapy for mediastinal lymphoma reduces significantly the dose to organs at risk and the integral body dose. It might lead to reduced late toxicities and secondary malignancies. This is especially important for children and young adults. It should be considered for both sexes, as both male and female patients benefit from the unique features of particle irradiation. Whenever proton for mediastinal lymphoma is not available or technical not feasible the alternative photon concepts have to be chosen carefully. Depending on the used technique certain organs at risk, i.e. the breasts in young females, can be spared with higher priority. However, with all photon techniques that comes at the cost of higher doses to the other organs at risk. If available, proton therapy should be the standard pattern of care for mediastinal lymphoma for young adults below 30 years of age, no matter if male or female.”

S. Lautenschlaeger, G. Iancu, V. Flatten, K. Baumann, M. Thiemer, C. Dumke, K. Zink, H. Hauswald, D. Vordermark, C. Mauz-Körholz, R. Engenhart-Cabillic & F. Eberle
Radiation Oncology volume 14, Article number: 157 (2019) 

https://ro-journal.biomedcentral.com/articles/10.1186/s13014-019-1360-7

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Montefiore Study May Help Establish Patient Criteria for Proton Therapy

N. Patrik Brodin, PhD

Data supporting the efficacy of proton therapy are robust for pediatric cancers, brain and base-of-skull tumors, and complex-shaped tumors near critical structures (…)

Proton therapy has emerged as an attractive option for patients with head and neck cancer. This is due to proton therapy beam technology, which precisely destroys cancers with an unmatched ability to stop at precise locations within the body.

Protons also have significantly fewer adverse effects (AEs) and toxicities than most other cancer therapies, because of the protons’ unique ability to sculpt radiation doses according to the shapes and sizes of tumors. This is particularly important for head and neck cancers, which frequently are close to or impeding on vocal cords, air passageways, swallowing muscles, salivary glands, and the oral mucosa. The opportunity to preserve healthy tissue is considerable.

AEs estimated to be significantly less prominent include swallowing difficulties, inflammation of the esophagus, and reduced saliva production. For people suffering from head and neck cancer and their families, the ability to avoid these types of complications makes an overwhelmingly important difference in QoL.

Younger patients, non-smokers, and patients with HPV p16- positive tumors will most likely benefit from proton therapy (…)

The highest expense in cancer therapy involves the regrowth of cancer—large sums are required to prolong survival and maintain QoL. By increasing cure rates and improving patients’ QoL, we can increase cost-effectiveness.

It is important for healthcare providers not only to educate our patients and their families about each treatment’s ability to destroy cancers, but also to manage expectations about different treatments and what life may look like “post cancer.”

Proton therapy is one of the most modern therapies available, and its ability to minimize AEs such as trouble swallowing, reduced ability to eat, dental problems, and difficulty digesting food can’t be understated for some of our patients (…) By increasing cure rates and improving patients’ Quality of Life, we can increase cost-effectiveness.

https://www.onclive.com/publications/oncology-live/2019/vol-20-no-11/montefiore-study-may-help-establish-patient-criteria-for-proton-therapy

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Dosimetric studies show that proton therapy can reduce the low/intermediate radiation dose to uninvolved tissue in children with low-grade glioma (LGG).

Outcomes Following Proton Therapy for Pediatric Low-Grade Glioma Indelicato, Daniel J. et al. International Journal of Radiation Oncology • Biology • Physics , Volume 104 , Issue 1 , 149 – 156.

Low-grade gliomas (LGGs) are the most common brain tumors in children, with approximately 800 cases diagnosed each year in the United States. Management of these tumors depends on several elements, including host factors (eg, patient age and comorbidities) and disease characteristics (eg, tumor location and histologic subtype). With a long-term survival rate that exceeds 90%, therapy selection involves careful consideration of minimizing late toxicity from surgery, chemotherapy, and irradiation. Treatment side effects can be permanent or life threatening and include neurocognitive impairment, neurologic deficits, neurovascular compromise, neuroendocrine deficiency, and second malignancies.

Surgery, radiation therapy, and chemotherapy may be used as solitary therapies or in combination, offering different therapeutic ratios depending on the setting. As a result, establishing the ideal treatment choice and sequencing has historically been an area of controversy, presenting challenges that are further complicated by the emergence of molecular targets.

Several studies have attempted to mitigate the impact of late radiation toxicity through selective radiation avoidance, systematic reduction in the size of target volumes, and the use of advanced radiation techniques. Of these radiation techniques, proton therapy is particularly promising because it allows for reductions in the low and intermediate radiation dose to normal tissue outside of the target volume. Accordingly, LGGs in children are considered a “Group 1” indication for proton therapy according to the United States American Society for Radiation Oncology Model Policy, and they have become the third most common pediatric brain tumor type treated with proton therapy worldwide.

Compared with modern photon series, proton therapy reduces the radiation dose to developing brain tissue, diminishing acute toxicities without compromising disease control.

https://www.redjournal.org/article/S0360-3016(19)30162-2/pdf

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What is the best therapeutic approach to a pediatric patient with a deep-seated brain Arteriovenous Malformations ?

Meling TRPatet G

Proton Therapy offers promising results with a more accurate radiation that avoids the surrounding tissue

Although brain arteriovenous malformations (bAVMs) account for a very small proportion of cerebral pathologies in the pediatric population, they are the cause of roughly 50% of spontaneous intracranial hemorrhages. Pediatric bAVMs tend to rupture more frequently and seem to have higher recurrence rates than bAVMs in adults. Thus, the management of pediatric bAVMs is particularly challenging. In general, the treatment options are conservative treatment, microsurgery, endovascular therapy (EVT), gamma knife radiosurgery (GKRS), proton-beam stereotactic radiosurgery (PSRS), or a combination of the above. In order to identify the best approach to deep-seated pediatric bAVMs, we performed a systematic review, according to the PRISMA guidelines. None of the options seem to offer a clear advantage over the others when used alone. Microsurgery provides the highest obliteration rate, but has higher incidence of neurological complications. EVT may play a role when used as adjuvant therapy, but as a stand-alone therapy, the efficacy is low and the long-term side effects of radiation from the multiple sessions required in deep-seated pediatric bAVMs are still unknown. GKRS has a low risk of complication, but the obliteration rates still leave much to be desired. Finally, PSRS offers promising results with a more accurate radiation that avoids the surrounding tissue, but data is limited due to its recent introduction. Overall, a multi-modal approach, or even an active surveillance, might be the most suitable when facing deep-seated bAVM, considering the difficulty of their management and the high risk of complications in the pediatric population.

Neurosurg Rev. 2019 Jun;42(2):409-416. https://www.ncbi.nlm.nih.gov/pubmed/30980204

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