Acute toxicities in proton therapy for head and neck cancer - A matched analysis of the DAHANCA 35 feasibility study.

Background and purpose: As preparation for a national randomized study comparing proton radiotherapy to photon radiotherapy, DAHANCA 35, we performed a non-randomized pilot study to investigate patient selection, logistics, planning, and treatment delivery. With the present study, as a comprehensive safety analysis, we want to compare toxicity during and up to two months after therapy to a historically matched group of patients treated with photon radiotherapy. Materials and methods: 62 patients treated with protons were matched to 124 patients who received photon treatment outside a protocol. Available data were retrieved from the DAHANCA database. Patients were matched on treatment centre, concurrent chemotherapy, tumour site, stage, p16 status for oropharynx cancers. Selection of patients for proton therapy was based on comparative treatment plans with a NTCP reduction for dysphagia and xerostomia at six months. Results: Baseline characteristics between groups were well balanced, except for the type of drug used concurrently; more photon patients received Carboplatin (21.2 % vs 5.8 %, p = 0.01). Proton therapy was associated with significantly less weight loss at the end of treatment, mean weight loss of 3 % for protons and 5 % for photons (p < 0.001). There were more grade 3 skin reactions and grade 3 mucositis after proton treatment compared with photons at the end of treatment, Risk Ratio (RR) 1.9 (95 % CI: 1.01-3.5, p = 0.04) and RR 1.5 (95 % CI: 1.3-1.7, p < 0.001), respectively. All differences resolved at follow up two months after treatment. There were no significant differences between groups on opioid use, use of feeding tubes, or hospitalization during the observation period. Conclusion: Proton treatment resulted in excess objective mucositis and dermatitis, which was transient and did not seem to negatively influence weight or treatment compliance and intensity. Selection bias was likely especially since NTCP models were used for selection of proton treatment and photon treated patients were matched manually. We are currently including patients in a randomized controlled trial.

Considerations for study design in the DAHANCA 35 trial of protons versus photons for head and neck cancer.

Proton radiotherapy offers a dosimetric advantage compared to photon therapy in sparing normal tissue, but the clinical evidence for toxicity reductions in the treatment of head and neck cancer is limited. The Danish Head and Neck Cancer Group (DAHANCA) has initiated the DAHANCA 35 randomised trial to clarify the value of proton therapy (NCT04607694). The DAHANCA 35 trial is performed in an enriched population of patients selected by an anticipated benefit of proton therapy to reduce the risk of late dysphagia or xerostomia based on normal tissue complication probability (NTCP) modelling. We present our considerations on the trial design and a test of the selection procedure conducted before initiating the randomised study.

Accurate in vivo dosimetry of a randomized trial of prostate cancer irradiation.

PURPOSE: To guarantee an accurate dose delivery, within +/- 2.5%, in a Phase III randomized trial of prostate cancer irradiation (68 vs. 78 Gy) by means of a comprehensive in vivo dosimetry program. METHODS AND MATERIALS: Prostate patients are generally treated in our clinic with a 3-field isocentric technique: an 8-MV anteroposterior beam and 2 18-MV wedged laterals. All fields are shaped conformally to the PTV. Patients were randomized between two dose levels of 68 Gy and 78 Gy. During treatment, the entrance and exit dose were measured for each patient with diodes. Special 2.5-mm thick steel build-up caps were applied to make the diodes appropriate for measurements in 18-MV photon beams as well. Portal images were used to verify the correct position of the diodes and to detect and correct for gas filling in the rectum that may influence the exit dose reading. Entrance and exit dose measurements were converted to midplane dose, which was used in combination with a depth dose correction to obtain the dose at the specification point. An action level of 2.5% was applied. RESULTS: The added build-up for the diodes in the 18-MV beams resulted in correction factors that were only slightly sensitive to changes in beam setup and comparable to the corrections used in the 8-MV beams for diodes without extra build-up. The calibration factor increased almost linearly with cumulative dose: 0.7%/kGy for the 8-MV and 1.2%/kGy for the 18-MV photon beams. The introduction of average correction factors made the analysis easier, while keeping the accuracy within acceptable limits. In a period of 3 years, 225 patients were analyzed, from which 8 patients needed to be corrected. The average ratio of measured and prescribed dose was 1.009 (standard deviation [SD] 0.012) for the total group treated on two linear accelerators. When the results were analyzed per accelerator, the ratios were 1.002 (SD, 0.001) for Accelerator A and 1.015 (SD, 0.001) for Accelerator B. This difference could be attributed to the cumulative effect of three small imperfections in the performance of Accelerator B that were well within the limits of our quality assurance program. CONCLUSION: Diodes can be used for accurate in vivo dosimetry during prostate irradiation in high-energy photon beams. The dose delivery in this randomized trial is guaranteed within the 2.5% limits on an individual patient basis. This could not be achieved without the in vivo dosimetry program, despite our high-standard quality assurance program of treatment delivery.

Interview: Beatrijs Smulders. Interview by Ina May Gaskin.

The Netherlands' stubborn refusal to march in lock-step with the rest of the industrialized world, when it comes to maternity care provides important lessons for other nations. Beatrijs Smulders, author of Baren ('Giving Birth') and producer of several videos on vertical home-birthing, has been working as an Amsterdam midwife since 1979 and today plays a leading role in Dutch midwifery. Here, she explores new territory through home birth, working toward a practice both less regulated by and less reliant on prevailing institutions.

[Reconstruction of the tibial plateau fracture with arthroscopic monitoring without arthrotomy]. / Reconstructie van de tibiaplateaufractuur onder artroscopische controle zonder artrotomie.

In the period from October 1986 to November 1988 in the Medisch Spectrum Twente of Enschede, 25 patients were treated for a tibial plateau fracture by means of arthroscopic surgery. The mean hospital stay was 18 days. Active movement of the leg was prescribed from the fifth day. The results were very good in 23 and poor in 2 patients. Complications such as wound infections and skin necrosis were not seen. Additional meniscal lesions could be diagnosed and treated better using this surgical technique. In addition, the limited incisions and consequently the avoidance of extensive arthrotomy allowed faster rehabilitation and a higher probability of healing the chondral tissue.