Proton Therapy Updates
January 2021

The aim of this newsletter is to promote knowledge on proton cancer therapy form a cross-disciplinary perspective: from development in equipment to impacts to healthcare.


We start the year 2021 with this Newsletter. In this introductory reflection, it is inevitable to mention that this has been the year of our clinical growth as a professional group and institutional project. 100 patients have been treated with proton therapy in the context of a major worldwide pandemic of COVID-19, which is still out of control. This context of socio-sanitary chaos highlights the commitment of each professional involved in the Proton Therapy Unit of the Cínica Universidad de Navarra.  It is exciting to witness the energy of the pioneers to succeed or to make corrections.

In the scientific field, there has been highlighted a surprising contribution on early stage lung cancer where the toxicity/control balance is decisive for the quality of survival. "The doubt is of the sages".  The discovery of images in the central nervous system of patients treated with photons or protons that are difficult to interpret, called "pseudo-progressions", deserves to be evaluated in-depth.

The dosimetric comparisons of different irradiation techniques are especially decisive in the rescue of relapses to previous radiotherapy. The special behavior of protons in the chest allows to further protect the heart and lungs. Finally, the tradition of medical care in proton therapy offers new opportunities for dosimetric individualisation in times of precision medicine. The experts of the University of Groningen add value by suggesting to recalculate individual doses taking into consideration the scales of expected toxicity in normal tissues.

The year 2020 has been a time of remarkable generosity in the efforts of all the professionals at the Clínica Universidad de Navarra. Congratulations to everybody! It is a memorable year.

Prof. Dr. Felipe Calvo Manuel 
Dr. Diego Azcona

Clinica Universidad de Navarra Proton Therapy Unit

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

The British Journal of Radiology

"In silico" studies allow for evaluations of potential clinical impact. Non-small cell lung cancer reiradiation is a high risk alternative in toxicity of normal tissues previously exposed to irradiation, which must be estimated before making an active clinical decision.

The dosimetric comparisons between various irradiation techniques in this scenario (three-dimensional conformational, volumetric arctherapy, intensity modulated, tomotherapy, cyberknife and proton therapy) and their impact on regions of anatomical interest show a greater benefit in the protection of the heart and lungs as organs at risk while using proton therapy.

Pseudoprogression after radiation therapies for low grade glioma in children and adults: A systematic review and meta-analysis

Radiotherapy and Oncology

“The doubt is of the sages”. In the treatment of low grade gliomas there are long-term survivors after treatment with radiotherapy who develop alterations in neuroimaging studies that are difficult to interpret. The simplified term used is "pseudo-progressions". In a systematic review of the scientific literature, 5 cohorts of pediatric patients and 4 cohorts of adult patients are analyzed: a total of 1041 patients.

An incidence of 33/34% of pseudo-progressions was observed (mostly visible 6-12 months after radiotherapy) in pediatric patients treated with IMRT photons/protons (adults 18% vs 30%). “Pseudo-progression" images are frequent in patients treated with low-grade gliomas with both photons and protons. Their significance and evolutionary impact is uncertain. This observation deserves a further analysis.

Feasibility of patient specific quality assurance for proton therapy based on independent dose calculation and predicted outcomes

Radiotherapy Oncology

Quality assurance in proton therapy has a level of instrumental control (the equipment used to calculate and administer the irradiation dose) and a level of control over the specific action on the patient (the determination of his individual dose).

The University of Groningen has implemented quality control of the individual patient dose in the medical care workflow by means of a "recalculation" taking into account the probability of normal tissue complications (NTCP) and tumour control (TCP) scales. An analysis model of 30 patients with head and neck cancer has shown the feasibility of this improvement (double calculation of the patient's individual dose by adding toxicity and tumour control scales) with a 2.7% coincidence.

Proton Beam Therapy for Histologically or Clinically Diagnosed Stage I Non-Small Cell Lung Cancer (NSCLC): The First Nationwide Retrospective Study in Japan

International Journal of Radiation Oncology, Biology and Physics

A 2010 meta-analysis concluded that patients with early stage lung cancer (stage IA and IB) treated with proton therapy or heavy ion therapy had a comparable outcome pattern to treatment with photon techniques. In 2020, 8 Japanese institutions are retrospectively studying 669 patients with 682 stage I lung cancers (clinical or histological diagnosis 64%).

With an average effective biological dose of 109.6 GyE, the grade 3-4 toxicity rate is 0.4% (dermatitis) without observing grade 4 pneumonitis. After 3 years of monitoring, local control is 89.8% and survival is 79.5%. The evidence provided by this study is decisive for incorporating early stage lung cancer (stage I) into the indications for proton therapy with mature clinical experience (multi-institutional, very large patient cohort and mature follow-up time).