Associations Between Mean Lung Dose and Prevalence of Radiation Pneumonitis in Elderly Lung Cancer Patients.

BACKGROUND/AIM: Pneumonitis is a serious radiotherapy complication. This study, which is a prerequisite for a prospective trial, aimed to identify the prevalence of pneumonitis and risk factors in elderly patients with lung cancer. PATIENTS AND METHODS: Ninety-eight lung cancer patients aged ≥65 years were included. Seventeen factors were investigated regarding grade ≥2 pneumonitis at 24 weeks following radiotherapy. RESULTS: The prevalence of grade ≥2 pneumonitis at 24 weeks was 27.3%. On univariate analysis, a significant association was observed for mean (ipsilateral) lung dose (MLD; ≤13.0 vs. 13.1-20.0 vs. >20.0 Gy; 0% vs. 24.9% vs. 48.7%). Results were significant also for ≤13.0 vs. >13.0 Gy (0% vs. 37.1%) or ≤20.0 vs. >20.0 Gy (13.4% vs. 48.7%). MLD achieved significance on multivariate analysis. CONCLUSION: Elderly patients receiving MLDs >13.0 Gy, particularly >20.0 Gy, have a high risk of grade ≥2 pneumonitis. These results are important for designing a prospective trial.

Clinically Significant Dermatitis During Adjuvant Radiotherapy for Invasive Breast Cancer.

BACKGROUND/AIM: Patients with breast cancer receiving adjuvant radiotherapy may experience grade ≥2 dermatitis. In the Interreg-project HeAT, a mobile application (app) reminding patients to perform skin care will be prospectively tested with the goal of decreasing clinically significant radiation dermatitis. This study aimed to identify the prevalence of grade ≥2 dermatitis and risk factors, required for designing the prospective trial. PATIENTS AND METHODS: In a retrospective study of 327 patients with breast cancer irradiated during 2022-2023, the prevalence of grade ≥2 dermatitis and 23 potential risk factors were investigated. RESULTS: The prevalence of grade ≥2 dermatitis was 31.2%. On multivariate analysis, it was significantly associated with chronic inflammatory disease (p=0.001), significant cardiovascular disease (p<0.001), smoking history >10 pack years (p<0.001), advanced T-stage (p=0.017), normo-fractionation (p<0.001), and radiation boost (p<0.001). CONCLUSION: The prevalence of grade ≥2 dermatitis and independent risk factors during adjuvant radiotherapy for invasive breast cancer were identified that contribute to improved patient care and the design of a prospective trial.

Comparison of the distribution of lymph node metastases compared to healthy lymph nodes in breast cancer.

BACKGROUND: Current literature lacks a comparison of lymph node metastases and non-pathological lymph nodes distribution in breast cancer patients. The aim of the current retrospective study was to generate a comprehensive atlas of the lymph node system. METHODS: 143 breast cancer patients underwent F-18-FDG-PET/CT (PET/CT) imaging for staging purposes and were diagnosed with regional lymph node metastases. Based on the PET/CT data set a total of 326 lymph node metastases and 1826 non-pathological lymph nodes were detected and contoured manually in the patient collective. Using rigid and deformable registration algorithms all structures were transferred to a template planning CT of a standard patient. Subsequently, a 3D-atlas of the distribution of lymph node metastases and non-pathological lymph nodes were generated and compared to each other. RESULTS: Both, lymph node metastases and non-pathological lymph nodes, accumulated in certain areas ("hot-spots") within the lymphatic drainage system. However large differences regarding the distribution patterns were detected: lymph node metastases hot spots occurred in close proximity to the subclavian vein in level I-III, whereas the non-pathological lymph nodes accumulated mostly (within a wider range) in level I. In level II and III lymph node metastases exceeded clearly the areas in which non-pathological lymph nodes occurred. CONCLUSION: Lymph node metastases and non-pathological lymph node distribution within the lymph node system differ clearly. Based on our results, an individual adjustment of the CTV in order to include visible lymph nodes in level II and III should be discussed.

Neuroanatomical changes seen in MRI in patients with cerebral metastasized breast cancer after radiotherapy.

PURPOSE: To quantify neuroanatomical changes using magnetic resonance imaging (MRI) in patients with cerebral metastasized breast cancer after brain radiotherapy (RT). METHODS: Fifteen patients with breast cancer with brain metastases who underwent whole brain RT (WBR), radiosurgery (RS), and/or hypofractionated stereotactic treatment (STX) were examined at four time points (TPs). A total of 48 MRIs were available: prior to RT (TP1), 5-8 months after RT (TP2), 9-11 months after RT (TP3), and >20 months after RT (TP4). Using automatic segmentation, 25 subcortical structures were analyzed. Patients were split into three groups: STX (receiving STX and RS), RS (receiving RS only), and WBR (receiving WBR at least once). After testing for a normal distribution for all values using the Kolmogorov-Smirnov test, a two-sided paired t test was used to analyze volumetric changes. For those values that were not normally distributed, the nonparametric Mann-Whitney test was employed. RESULTS: The left cerebellum white matter (p = 0.028), the right pallidum (p = 0.038), and the left thalamus (p = 0.039) significantly increased at TP2 compared to TP1. The third ventricle increased at all TPs (p = 0.034-0.046). The left choroid plexus increased at TP3 (p = 0.037) compared to TP1. The left lateral ventricle increased at TP3 (p = 0.012) and TP4 (p = 0.027). Total gray matter showed a trend of volume decline in STX and WBR groups. CONCLUSIONS: These findings indicate that alterations in the volume of subcortical structures may act as a sensitive parameter when evaluating neuroanatomical changes and brain atrophy due to radiotherapy. Differences observed for patients who received STX and WBR, but not those treated with RS, need to be validated further.

A Comprehensive Prospective Comparison of Acute Skin Toxicity after Hypofractionated and Normofractionated Radiation Therapy in Breast Cancer.

The current study aims to determine whether hypofractionated radiotherapy (HF) leads to lower rates of acute radiodermatitis compared to conventional normofractionated radiotherapy (CF). A total of 166 patients with invasive breast cancer or DCIS were included in a prospective cohort study. Evaluation of acute radiodermatitis was obtained before radiotherapy, at the end of the treatment (T1), and 6 weeks after the treatment (T2) using CTCAE (v5.0) scores, the Skindex-16 questionnaire, and ultrasound measurement of the skin. CTCAE and Skindex-16 scores in the CF-group were significantly higher compared to the HF group indicating more pronounced side effects at the end of the treatment (CTCAE: CF-RT 1.0 (IQR: 0.0) vs. HF-RT 0.0 (0.25); p = 0.03; Skindex-16: CF: 20.8 (IQR: 25.8); HF: 8.3 (27.1); p = 0.04). At 6 weeks after the treatment, no significant differences between the two fractionation schemes were observed. Ultrasound based assessment showed that the skin thickness in the treated breast was higher compared to the healthy breast at all time-points. However, no significant difference between HF and CF was seen either at T1 or T2. The current study complements and confirms pre-existing evidence that HF leads to a lower degree of acute radiodermatitis and better patient reported outcome compared to CF at the end of treatment. This should be considered whenever fractionation of adjuvant breast cancer treatment is being discussed.

Correlations of UICC tumor stage and tumor regression on T2-weighted MRI sequences during definitive radiotherapy of cervical cancer.

BACKGROUND: The purpose of this study is to detect a correlation between the preradiation tumor staging and the relative volumetric regression of the primary tumor through external beam radiation therapy (EBRT). METHODS: Clinical data of 32 patients with a mean age of 60±12 years treated with primary radiation therapy (RT) of cervical carcinoma were analyzed. Union Internationale Contre le Cancer (UICC) stages were T1 = 4 patients, T2 = 15 patients, T3 = 8 patients, T4 = 5 patients; N1 = 26 patients, N0 = 6 patients; and M0 = 25 patients, M1 = 7 patients. All patients received pelvic magnetic resonance imaging (MRI) before RT as well as during RT. The cervical primary tumor was delineated as gross tumor volume (ptGTV) in T2-weighted MRI sequences. We compared ptGTV reduction by stage, lymph node status, metastatic status, and grading. RESULTS: Mean ptGTV reduction during RT was 61.4±28.9%. T1 tumors shrank by 88.2±13.4%, T2 by 67.6±28.7%, T3 by 50.8±23.6%, and T4 by 38.7±27.2%. The difference in tumor shrinkage was statistically significant between the lower T stages and the higher T stages (p < 0.05). There was no statistical difference in the mean ptGTV before treatment in the group with lymph node metastases (LNM) (54.1±47.7 cm3) as compared to the group without LNM (76.6±52.2 cm3). Nonetheless, ptGTV shrank significantly differently: by 68.9±25.7% (N1 patients) and by 29.0±17.7% (N0 patients). No significant differences in ptGTV shrinkage were observed in M0 versus M1 and G2 versus G3 tumors. CONCLUSION: There is a correlation between mean ptGTV reduction during EBRT and tumor stages. Tumors with higher T stages shrank less under radiation treatment, and the ptGTV of N1 patients responded better than that of N0 patients.

Effect of hypofractionation on the incidental axilla dose during tangential field radiotherapy in breast cancer.

OBJECTIVE: Tangential field irradiation in breast cancer potentially treats residual tumor cells in the axilla after sentinel lymph node biopsy (SLNB). In recent years, hypofractionated radiotherapy has gained importance and currently represents the recommended standard in adjuvant breast cancer treatment for many patients. So far, the impact of hypofractionation on the effect of incidental lymph node irradiation has not be addressed. MATERIALS AND METHODS: Biological effective dose (BED) and tumor control probability (TCP) were estimated for four different hypofractionated radiation schemes (42.50 Gy in 16 fractions [Fx]; 40.05 Gy in 15 Fx; 27 Gy in 5 Fx; and 26 in 5 Fx) and compared to conventional fractionation (50 Gy in 25 Fx). For calculation of BED and TCP, a previously published radiobiological model with an α/ß ratio of 4 Gy was used. The theoretical BED and TCP for incidental irradiation between 0 and 100% of the prescribed dose were evaluated. Subsequently, we assessed BED and TCP in 431 axillary lymph node metastases. RESULTS: The extent of incidental lymph node irradiation and the fractionation scheme have a direct impact on BED and TCP. The estimated mean TCP in the axillary nodes ranged from 1.5 ± 6.4% to 57.5 ± 22.9%, depending on the patient's anatomy and the fractionation scheme. Hypofractionation led to a significant reduction of mean TCP of lymph node metastases for all schedules. CONCLUSION: Our data indicate that hypofractionation might affect the effectiveness of incidental radiotherapy in the axilla. This is particularly relevant for patients with positive sentinel lymph nodes who receive SLNB only.

Positive correlation between blood glucose and radiotherapy doses to the central gustatory system in Glioblastoma Multiforme patients.

BACKGROUND: The aim of this study was to assess the correlations between the levels of blood glucose (BG) and the dose of radiation therapy (RT) to the central gustatory system (GS) in glioblastoma multiforme (GBM) patients. METHODS: Thirty-seven GBM patients with regular blood glucose measurements were investigated retrospectively. 59.5% were female and 40.5% male with a median age of 64.3 years (range 27.4-85.6). Diabetes mellitus type 2 (DM2) history, BG levels and dexamethasone (DEXA) medication were assessed. The analyzed central gustatory structures were: solitary tract and nucleus, ventral posteromedial nucleus of the thalamus, sensory tongue area of the postcentral gyrus, anterior part of the insula, frontal operculum, amygdala, hypothalamus. These structures were delineated on magnetic resonance tomographies (MRIs) registered to planning-CTs. All GS doses were transformed in equivalent doses in 2 Gy fraction (EQD2). RESULTS: Twenty one patients (56.8%) had at least one BG values over 200 mg/dl during RT. There was a difference between average BG in DM2: 192.8 mg/dl (±24.4) and non-DM2 patients: 145.7 mg/dl (±39.5; p = 0.01) but no significant difference in daily DEXA medication - DM2 patients: 7.9 mg/d (±1.9) vs. non-DM2: 9.3 mg/dl (±5.7; p = 0.29). The EQD2 Dmean to the total GS was 36.0Gy (±8.6 Gy). There was a tendency for a higher increase in maximum BG values with more radiation dose to the total GS (b = 1.9, R2 = 0.103, p = 0.06). CONCLUSION: BG levels in GBM patients are in direct correlation to the dose of RT applied to the central GS. GBM patients that undergo RT should thus be closely monitored for changes in BG levels during and after the radiation.

Acute radiodermatitis in modern adjuvant 3D conformal radiotherapy for breast cancer - the impact of dose distribution and patient related factors.

PURPOSE: This study was performed to evaluate skin toxicity during modern three-dimensional conformal radiotherapy (3D-CRT) and to evaluate the importance of dose distribution and patient related factors. MATERIAL AND METHODS: This study comprises 255 patients with breast cancer treated with tangential three-dimensional conformal radiotherapy (3D-CRT) after breast conserving surgery between 03/2012 and 05/2017. The median prescribed dose was 50.4 Gy (range 50-50.4) and 92.2% of the patients received a sequential boost of 10-16 Gy. Adverse skin toxicities (according to CTCAE v. 4.03 and the occurrence of moist desquamations) were assessed at the end of treatment. The dose distribution in the skin (5 mm strip from the patient outline) and in the CTV was evaluated and correlated to the CTCAE scores and the occurrence of moist desquamation. RESULTS: 42.4% of the patients developed grade I, 55.7% grade II and 2% grade III skin toxicities. Moist desquamation was observed in 59 cases (23.1%). Dose distribution within the CTV and skin was homogenous with only small areas receiving 107% of the prescribed dose (median: 0.7 cm3) in the CTV and 105% (median 0.5 cm3) in the skin. On univariate analysis breast size as well as V107%(CTV), V105%(skin) and V80%(skin) correlated significantly (p < 0.05) with the incidence of skin toxicity. On multivariate analysis only V80%(skin) was confirmed as independent risk factor. CONCLUSION: Modern tangential multi-field 3D-CRT allows a homogeneous dose distribution with similar skin toxicity as compared to studies performing IMRT. Dose distribution within the skin (V80%) might have a relevant impact on the severity of skin toxicity and the occurrence of moist desquamation.

Effects of definitive and salvage radiotherapy on the distribution of lymphocyte subpopulations in prostate cancer patients.

BACKGROUND: Radiotherapy (RT) is an established treatment for patients with primary and recurrent prostate cancer. Herein, the effects of definitive and salvage RT on the composition of lymphocyte subpopulations were investigated in patients with prostate cancer to study potential immune effects. PATIENTS AND METHODS: A total of 33 prostate cancer patients were treated with definitive (n = 10) or salvage RT (n = 23) after biochemical relapse. The absolute number of lymphocytes and the distribution of lymphocyte subpopulations were analyzed by multiparameter flow cytometry before RT, at the end of RT, and in the follow-up period. RESULTS: Absolute lymphocyte counts decreased significantly after RT in both patient groups and a significant drop was observed in the percentage of B cells directly after RT from 10.1 ± 1.3 to 6.0 ± 0.7% in patients with definitive RT and from 9.2 ± 0.8 to 5.8 ± 0.7% in patients with salvage RT. In contrast, the percentages of T and natural killer (NK) cells remained unaltered directly after RT in both patient groups. However, 1 year after RT, the percentage of CD3+ T cells was significantly lower in patients with definitive and salvage RT. The percentage of regulatory T cells was slightly upregulated in primary prostate cancer patients after definitive RT, but not after salvage RT. CONCLUSION: Definitive and salvage RT exert similar effects on the composition of lymphocyte subpopulations in prostate cancer patients. Total lymphocyte counts are lower in both patient groups compared to healthy controls and further decreased after RT. B cells are more sensitive to definitive and salvage RT than T and NK cells.

Comparative analysis of the effects of radiotherapy versus radiotherapy after adjuvant chemotherapy on the composition of lymphocyte subpopulations in breast cancer patients.

BACKGROUND: Breast cancer is the most common cancer in women worldwide and surgery, radiotherapy (RT) and chemotherapy (ChT) are frequently used to treat this cancer. Adjuvant RT has been shown to cause long-term changes in lymphocyte counts in the peripheral blood. Herein, the time course of changes in lymphocyte subpopulations upon RT was studied in patients with and without adjuvant ChT in order to explore its potential clinical impact. MATERIALS AND METHODS: Total lymphocyte counts and the composition of lymphocyte subpopulations before RT (t0), after 30 Gy (t1), at the end of RT (t2), and 6 weeks (t3), 6 months (t4), and 1 year (t5) after RT were studied by flow cytometry. RESULTS: Absolute lymphocyte counts were significantly lower in all breast cancer patients (n=40) before and also 1 year after RT compared to healthy controls. The percentage of CD3(+)/CD4(+) helper T cells and FoxP3(+) regulatory T cells increased significantly in patients without adjuvant ChT. Different NK cell subpopulations dropped during RT in patients with and without ChT, but recovered to initial levels 6months after RT (t4). During RT (t0-t2) the percentage of CD19(+) B cells significantly dropped in patients without ChT, but gradually increased in patients with adjuvant ChT. Both patient groups reached initial levels 6 months after RT (t4). CONCLUSION: Different lymphocyte subpopulations respond differently to RT with and without adjuvant ChT. CD4(+) T cells increase during RT, whereas NK cells and B cells decrease in patients without ChT, but recover within 6 months after RT. Treg cells gradually increase in patients without ChT from t0 to t5, but not in patients with adjuvant ChT.

Measurements to predict the time of target replacement of a helical tomotherapy.

Intensity-modulated radiation therapy (IMRT) requires more beam-on time than normal open field treatment. Consequently, the machines wear out and need more spare parts. A helical tomotherapy treatment unit needs a periodical tungsten target replacement, which is a time consuming event. To be able to predict the next replacement would be quite valuable. We observed unexpected variations towards the end of the target lifetime in the performed pretreatment measurements for patient plan verification. Thus, we retrospectively analyze the measurements of our quality assurance program. The time dependence of the quotient of two simultaneous dose measurements at different depths within a phantom for a fixed open field irradiation is evaluated. We also assess the time-dependent changes of an IMRT plan measurement and of a relative depth dose curve measurement. Additionally, we performed a Monte Carlo simulation with Geant4 to understand the physical reasons for the measured values. Our measurements show that the dose at a specified depth compared to the dose in shallower regions of the phantom declines towards the end of the target lifetime. This reproducible effect can be due to the lowering of the mean energy of the X-ray spectrum. These results are supported by the measurements of the IMRT plan, as well as the study of the relative depth dose curve. Furthermore, the simulation is consistent with these findings since it provides a possible explanation for the reduction of the mean energy for thinner targets. It could be due to the lowering of low energy photon self-absorption in a worn out and therefore thinner target. We state a threshold value for our measurement at which a target replacement should be initiated. Measurements to observe a change in the energy are good predictors of the need for a target replacement. However, since all results support the softening of the spectrum hypothesis, all depth-dependent setups are viable for analyzing the deterioration of the tungsten target. The suggested measurements and criteria to replace the target can be very helpful for every user of a TomoTherapy machine.