Jon Espen Dale

The clinical application of different relative biological effectiveness (RBE) models for carbon ion RBE-weighted dose calculation hinders a global consensus in defining normal tissue constraints. This work aims to update the local effect model (LEM)-based constraints for the rectum using microdosimetric kinetic model (mMKM)-defined values, relying on RBE translation and the analysis of long-term clinical outcomes. LEM-optimized plans of treated patients, having suffered from prostate adenocarcinoma (n = 22) and sacral chordoma (n = 41), were recalculated with the mMKM using an in-house developed tool. The relation between rectum dose-volume points in the two RBE systems (D_LEM|v and D_MKM|v) was fitted to translate new LEM-based constraints. Normal tissue complication probability (NTCP) values, predicting late rectal toxicity, were obtained by applying published parameters. No late rectal toxicity events were reported within the patient cohort. The rectal toxicity outcome was confirmed using dosimetric analysis: D_MKMVHs lay largely below original constraints; the translated D_LEM|v values were 4.5%, 8.3%, 18.5%, and 35.4% higher than the nominal D_MKM|v of the rectum volume, v—1%, 5%, 10% and 20%. The average NTCP value ranged from 5% for the prostate adenocarcinoma, to 0% for the sacral chordoma group. The redefined constraints, to be confirmed prospectively with clinical data, are D_LEM|5cc ≤ 61 Gy(RBE) and D_LEM|1cc ≤ 66 Gy(RBE).

Radiation therapy for cancer is considered to be immunosuppressive. However, the cellular response after radiation therapy may stimulate or suppress an immune response. The effect may vary with the tumor type and occasionally tumor regressions have been observed outside the irradiated volume, both in animal studies and in the clinic. A renewed interest in the role of immunity for the observed effect of radiation came with the current recognized role of immune checkpoint blockers (ICBs) for control of selected cancer types. We therefore here review preclinical studies and clinical reports on the interaction of ICBs and radiation as a basis for further clinical trials. Some tumor types where the combination of these modalities seems especially promising are also proposed.

The relative biological effectiveness (RBE) of protons varies with multiple physical and biological factors. Phenomenological RBE models have been developed to include such factors in the estimation of a variable RBE, in contrast to the clinically applied constant RBE of 1.1. In this study, eleven published phenomenological RBE models and two plan-based models were explored and applied to simulated patient cases. All models were analysed with respect to the distribution and range of linear energy transfer (LET) and reference radiation fractionation sensitivity (( α / β ) _x ) of their respective experimental databases. Proton therapy plans for a spread-out Bragg peak in water and three patient cases (prostate adenocarcinoma, pituitary adenoma and thoracic sarcoma) were optimised using an RBE of 1.1 in the Eclipse ^™ treatment planning system prior to recalculation and modelling in the FLUKA Monte Carlo code. Model estimated dose-volume parameters for the planning target volumes (PTVs) and organs at risk (OAR) were compared. The experimental in vitro databases for the various models differed greatly in the range of ( α / β ) _x values and dose-averaged LET (LET _d ). There were significant variations between the model estimations, which arose from fundamental differences in the database definitions and model assumptions. The greatest variations appeared in organs with low ( α / β ) _x and high LET _d , e.g. biological doses given to late responding OARs located distal to the target in the treatment field. In general, the variation in maximum dose (D _2% ) was larger than the variation in mean dose and other dose metrics, with D _2% of the left optic nerve (( α / β ) _x = 2.1 Gy) in the pituitary adenoma case showing the greatest discrepancies between models: 28–52 Gy(RBE), while D _2% for RBE _1.1 was 30 Gy(RBE). For all patient cases, the estimated mean RBE to the PTV was in the range 1.09–1.29 (( α / β ) _x = 1.5/3.1/10.6 Gy). There were considerable variations between the estimations of RBE and RBE-weighted doses from the different models. These variations were a consequence of fundamental differences in experimental databases, model assumptions and regression techniques. The results from the implementation of RBE models in dose planning studies should be evaluated in light of these deviations.

Background: Many patients are diagnosed with an anal cancer in high ages. We here present the outcome after oncological therapy for patients above 80 years compared with younger patients. Materials and methods: A series of 213 consecutive patients was diagnosed and treated at a single institution from 1984 to 2009. The patients received similar radiation doses but with different techniques, thus progressively sparing more normal tissues. The majority of patients also had simultaneous [5-fluorouracil (5FU) and mitomycin C] or induction chemotherapy (cisplatin and 5FU). The patients were stratified by age above or below 80 years. Despite that the goal was to offer standard chemoradiation treatment to all, the octo- and nonagenarians could not always be given chemotherapy. Results: In our series 35 of 213 anal cancer patients were above 80 years. After initial therapy similar complete response was observed, 80% above and 87% below 80 years. Local recurrence rate was also similar in both groups, 21% versus 26% (p = .187). Cancer-specific survival and relative survival were significantly lower in patients above 80 years, 60% and 50% versus 83% and 80%, (p = .015 and p = .027), respectively. Conclusion: Patients older than 80 years develop anal cancer, but more often marginal tumors. Even in the oldest age group half of the patients can tolerate standard treatment by a combination of radiation and chemotherapy, and obtain a relative survival of 50% after five years. Fragile patients not considered candidates for chemoradiation may be offered radiation or resection to control local disease.