Long-term serum platinum changes and their association with cisplatin-related late effects in testicular cancer survivors

<p><b>Background:</b> The long-term toxicities after cisplatin-based chemotherapy (CBCT) reveal a remarkable inter-individual variation among testicular cancer survivors (TCSs). Therefore, we assessed long-term platinum (Pt) changes and their associations with CBCT-related late effects in TCSs.</p> <p><b>Material and methods:</b> In 77 TCSs treated with CBCT from 1984 to 1990, blood samples for analyses of Pt and a questionnaire including self-reported neuro- and ototoxicity (NTX) symptoms were collected during two follow-up surveys at median 12 (Survey I; SI) and 20 (Survey II; SII) years after treatment. Information about second cancers after SII was retrieved from the Norwegian Cancer Registry.</p> <p><b>Results:</b> A larger Pt decline from SI to SII was associated with a decreased risk of a second cancer diagnosis (HR 0.78, 95% CI 0.62–0.99 per 10 ng/L/year), and worsening of paresthesias in hands (OR 1.98, 95% CI 1.09–3.59 per 10 ng/L/year) and tinnitus (OR 1.51, 95% CI 1.01–2.27 per 10 ng/L/year).</p> <p><b>Conclusion:</b> In summary, we found a significant association between a larger Pt decline and a reduced risk of second cancers and deterioration of paresthesias in hands and tinnitus.</p

Linear energy transfer distributions in the brainstem depending on tumour location in intensity-modulated proton therapy of paediatric cancer

<p><b>Background:</b> For tumours near organs at risk, there is concern about unintended increase in biological dose from elevated linear energy transfer (LET) at the distal end of treatment fields. The objective of this study was therefore to investigate how different paediatric posterior fossa tumour locations impact LET and biological dose to the brainstem during intensity-modulated proton therapy (IMPT).</p> <p><b>Material and methods:</b> Multiple IMPT plans were generated for four different simulated tumour locations relative to the brainstem for a five-year-old male patient. A prescribed dose of 59.4 Gy(RBE) was applied to the planning target volumes (PTVs). Plans with two lateral and one posterior non-coplanar fields were created, along with plans with modified field arrangements. The dose-averaged LET (LET_d) and the physical dose × RBE_LET (<i>D</i> × RBE_LET), where RBE_LET=1+<i>c</i> × LET_d, were calculated using the FLUKA Monte Carlo code. A scaling parameter <i>c</i> was applied to make the RBE_LET represent variations in the biological effect due to LET.</p> <p><b>Results:</b> High LET_d values surrounded parts of the PTV and encompassed portions of the brainstem. Mean LET_d values in the brainstem were 3.2–6.6 keV/μm. The highest absolute brainstem LET_d values were seen with the tumour located most distant from the brainstem, whereas lower and more homogeneous LET_d values were seen when the tumour invaded the brainstem. In contrast, the highest mean <i>D</i> × RBE_LET values were found in the latter case (54.0 Gy(RBE)), while the case with largest distance between tumour and brainstem had a mean <i>D</i> × RBE_LET of 1.8 Gy(RBE).</p> <p><b>Conclusions:</b> Using IMPT to treat posterior fossa tumours may result in high LET_d values within the brainstem, particularly if the tumour volume is separated from the brainstem. However, the <i>D</i> × RBE_LET was greater for tumours that approached or invaded the brainstem. Changing field angles showed a reduction of LET_d and <i>D</i> × RBE_LET in the brainstem.</p

Estimated risk of radiation-induced cancer following paediatric cranio-spinal irradiation with electron, photon and proton therapy

<div><p></p><p><b>Background.</b> Improvement in radiotherapy during the past decades has made the risk of developing a radiation-induced secondary cancer as a result of dose to normal tissue a highly relevant survivorship issue. Important factors expected to influence secondary cancer risk include dose level and dose heterogeneity, as well as gender and type of tissue irradiated. The elevated radio-sensitivity in children calls for models particularly tailored to paediatric cancer patients.</p><p><b>Material and methods.</b> Treatment plans of six paediatric medulloblastoma patients were analysed with respect to secondary cancer risk following cranio-spinal irradiation (CSI), using either: 1) electrons and photons combined; 2) conformal photons; 3) double-scattering (DS) protons; or 4) intensity-modulated proton therapy (IMPT). The relative organ equivalent dose (OED) concept was applied in three dose-risk scenarios: a linear response model, a plateau response and an organ specific linear-exponential response. Life attributable risk (LAR) was calculated based on the BEIR VII committee's preferred models for estimating age- and site-specific solid cancer incidence. Uncertainties in the model input parameters were evaluated by error propagation using a Monte Carlo sampling procedure.</p><p><b>Results.</b> Both DS protons and IMPT achieved a significantly better dose conformity compared to the photon and electron irradiation techniques resulting in a six times lower overall risk of radiation-induced cancer. Secondary cancer risk in the thyroid and lungs contributed most to the overall risk in all compared modalities, while no significant difference was observed for the bones. Variations between DS protons and IMPT were small, as were differences between electrons and photons.</p><p><b>Conclusion.</b> Regardless of technique, using protons decreases the estimated risk of secondary cancer following paediatric CSI compared to conventional photon and electron techniques. Substantial uncertainties in the LAR estimates support relative risk comparisons by OED.</p></div