Clinical and Translational Radiation Oncology最新文献

Purpose

The aim of this study is to evaluate the cosmetic outcome among early stage breast cancer patients who underwent accelerated partial breast irradiation with either intraoperative electron radiotherapy (IOERT) or photon external beam radiotherapy (EB-APBI).

Materials and methods

This prospective multicenter cohort study enrolled women aged 60 years and older who underwent breast-conserving therapy. Following breast-conserving surgery, patients were treated with either IOERT or EB-APBI. Cosmetic outcome was evaluated over a 5 year follow-up period using both subjective scoring by patients and physicians, as well as objective scoring using BCCT.core software. Differences between treatments over time were described with mixed model analyses.

Results

A total of 241 patients treated with IOERT and 164 patients treated with EB-APBI were eligible for cosmetic analysis. In both groups, the majority of patients reported a satisfactory cosmetic outcome, with no significant differences between treatments over time (p = 0.538). This was also observed by physicians, with satisfactory outcomes ranging from 94 % (170/181) to 91 % (69/76) over time in the IOERT group and from 93 % (124/133) to 95 % (54/57) in the EB-APBI group (p = 0.579). BCCT.core analysis returned satisfactory cosmetic outcomes in 75 % (54/72) of the IOERT patients at 3 years and in 77 % (20/26) at 5 years. These numbers were 86 % (72/84) and 90 % (36/40) for the EB-APBI patients, with no significant differences between treatment over time (p = 0.834).

Conclusion

Regarding the cosmetic results, IOERT and EB-APBI yield comparable and satisfactory outcomes over 5 years follow-up in the treatment of early stage breast cancer.

Objective

Hypofractionation has become the new clinical standard for prostate cancer. We investigated the management of acute toxicity in patients treated with moderate hypofractionation (MHF) or Ultrahypofractionation (UHF).

Methods

In a prospective cohort setting, patients (N=316) received either MHF (20 fractions of 3/3.1 Gy, 5 fractions per week, N=156) or UHF (7 fractions of 6.1 Gy, 3 fractions per week, N=160) to the prostate +/- (base of the) seminal vesicles between 2019 and 2023. UHF was not indicated in case of significant lower urinary tract symptoms (LUTS) or T3b disease. Patient-reported outcomes (PRO) were online distributed at baseline, end of treatment (aiming at last fraction +/- 3 days), 3 months. Acute toxicity rates, management, and associations with baseline factors were analysed using Chi-square test and logistic regression. CTCAE scores (version 5) were calculated.

Results

Treatment for acute urinary complaints was prescribed in 46 % (MHF) and 29 % (UHF). Taking into consideration baseline LUTS, MHF and UHF showed similar rates of PROs and management. Medication for acute gastrointestinal (GI) symptoms was prescribed for 21.1 % (MHF) and 14.1 % (UHF) with more loperamide for diarrhea in MHF (9.0 %) vs UHF (1.9 %, p = 0.005). Grade ≥ 2 (MHF / UHF) was scored in 40 % / 28 % for GI (p = 0.03) and 50 % / 31 % for GU (p < 0.01). PROs for GI reported after last fraction of UHF were significantly worse compared to before last fraction.

Conclusion

UHF was safe with respect to acute toxicity risks in the selected population. MHF is associated with risks of significant diarrhea which needs further investigation. Furthermore, optimal registration of acute toxicity for UHF requires measurements up to 1–2 weeks after the last fraction.

Background and purpose

Data is needed regarding the use of ultrahypofractionated radiotherapy (UHRT) in the context of prostate cancer elective nodal irradiation (ENI), and how this compares to conventionally fractionated radiotherapy (CFRT) ENI with CFRT or moderately hypofractionated radiotherapy (MHRT) to the prostate.

Materials and methods

Between 2011–2019, 3 prospective clinical trials of unfavourable intermediate or high-risk prostate cancer receiving CFRT (78 Gy in 39 fractions to prostate; 46 Gy in 23 fractions to pelvis), MHRT (68 Gy in 25 fractions to prostate; 48 Gy to pelvis), or UHRT (35–40 Gy in 5 fractions to prostate +/- boost to 50 Gy to intraprostatic lesion; 25 Gy to pelvis) were conducted. Primary endpoints included biochemical failure (Phoenix definition), and acute and late toxicities (CTCAE v3.0/4.0).

Results

Two-hundred-forty patients were enrolled: 90 (37.5 %) had CFRT, 90 (37.5 %) MHRT, and 60 (25 %) UHRT. Median follow-up time was 71.6 months (IQR 53.6–94.8). Cumulative incidence of biochemical failure (95 % CI) at 5-years was 11.7 % (3.5–19.8 %) for CFRT, 6.5 % (0.8–12.2 %) MHRT, and 1.8 % (0–5.2 %) UHRT, which was not significantly different between treatments (p = 0.38). Acute grade ≥ 2 genitourinary toxicity was significantly worse for UHRT versus CFRT and MHRT, but not for acute grade ≥ 3 genitourinary, or acute gastrointestinal toxicities. UHRT was not associated with worse late toxicities.

Conclusion

ENI with UHRT resulted in similar oncologic outcomes to CFRT ENI with prostate CFRT/MHRT, with worse acute grade ≥ 2 GU toxicity but no differences in late toxicity. Randomized phase 3 trials of ENI using UHRT techniques are much anticipated.

Background

For adult patients with grade 1–3 gliomas, identifying patients with an indication for proton therapy (PT) can be challenging due to sparse evidence supporting its benefits. In this study, we aimed to ensure national consensus and develop a decision support tool to aid clinicians in identifying patients with grade 1–3 gliomas eligible for PT.

Methods

Sixty-one historic patients referred for postoperative radiotherapy for glioma grade 1–3 were included in this study and had new photon therapy and PT plans calculated. These plans along with clinical parameters were presented to neurooncologists with experience in treating brain tumours. The patients were presented at three workshops (WSs), where each neurooncologist individually had to choose between photon and proton therapy. Important parameters were selected using cross validation. Multivariable logistic regression was used to predict the neurooncologists’ treatment modality choice.

Results

At the three WSs 23, 24 and 19 randomly selected patients were presented. Seventy-five percent of the neurooncologists agreed for 14 patients (61%), 16 patients (67%) and 15 patients (79%) at WS1, WS2 and WS3. Age at radiotherapy and difference in mean dose (ΔDmean) to the residual brain were significant predictors of the choice of treatment modality, p < 0.001. Model coefficients were: β_age = 0.07 per year (95% confidence interval [CI] = 0.05–0.09), and β_Δdose = -0.27 per Gy (95% CI=-0.36--0.18).

Conclusion

Higher degree of agreement was reached. Age and ΔDmean to the residual brain significantly predicted the choice of radiation modality. We have developed a decision support model which may aid in the selection of patients with glioma grade 1–3 to PT.

Purpose

In France, radiation oncologists are predominantly men with only 44 % of women. Many studies have highlighted gender disparities in medicine. The main objective of our study was to assess the impact of discriminations on radiation oncologists’ career.

Materials and methods

An anonymous online questionnaire, adapted from the one used by the ESMO W4O group, was sent to all radiation oncologists in France between March and June 2022. It included questions related to professional experience, gender, socio-ethnicity, sexual orientation, and personal life.

Results

Among the 999 radiation oncologists and 168 residents in France, 225 questionnaires were collected (19.2 %). Among the respondents, 60 % were women and 25 % were residents. The mean age was 39.2 years (range: 25–78). The career satisfaction rate was 92 %, with no gender difference. Gender was considered to have a negative impact on the career development by 65 % of women. Social origin was an obstacle to career development for 37 % of all the respondents, and ethnic origin for 25 %. Sixty two percent of women reported having experienced inappropriate behavior or sexual harassment in their workplace, 38 % felt that having a child had “extremely“ or ”very“ much impacted their career versus 8.5 % of men (p < 0.001). The most popular proposals for improvement were the creation of a network of women radiation oncologists with specific educational programs and the addition of quotas in institutions and key positions.

Conclusions

This study is the first one assessing the various type of discrimination experienced by radiation oncologists in France. We make a few proposals for improvement of training and working conditions, regardless of the origin and gender.

Aims

Multidisciplinary tumor boards (MDTs) are an integral part of ensuring high-quality, evidence-based and personalized cancer care. In this study, we aimed to evaluate the adherence to and implementation of MDT recommendations in patients with oligometastatic disease (OMD).

Methods

We screened all oncologic positron emission tomography (PET) scans conducted at a single comprehensive cancer center in 2020. Patients were included if they had evidence of imaging-based OMD from a solid organ malignancy on the index scans, had their OMD case discussed at an MDT, and were treated and followed up at the same center. A switch away from the MDT-recommended treatment modalities was classified as a major deviation; non-MDT-mandated adjustments to a recommended treatment modality were coded as minor deviation. Clinical data was obtained via chart review; statistical calculations were computed using the R software.

Results

After review of PET and/or concurrent brain scans, 787 cases of OMD were identified. Thereof, 347 (44.1 %) cases were discussed at MDT, of which 331 (42.1 %) were therapeutically managed and subsequently followed. The three most commonly recommended therapies were systemic therapy (35.6 %), multimodality treatment including definitive local therapy (17.8 %), and radiotherapy (13.9 %). A major deviation was recorded in 16.3 % of cases (most commonly: none of the MDT-recommended treatment modalities were performed: 19 (35.2 %); not all MDT-planned treatment modalities were performed: 12 (22.2 %); and additional treatment modality was performed: 11 (20.3 %). A minor deviation was found in 1.5 % of cases. On multivariable regression, number of distant metastases (n > 1) was associated with a major deviation (OR: 1.85; 95 % CI, 1.0–3.52). Major deviations were associated with a significantly worse OS (p = 0.0034).

Conclusions

Adherence to and implementation of MDT recommendations in OMD patients was generally high (83.7%). Major deviations might be further reduced by more careful and elaborate discussions of OMD patient characteristics s and patient preferences.

This study evaluates the benefit of weekly delineation and peer review by a multidisciplinary team (MDT) of radiation oncologists (ROs), radiologists (RXs), and nuclear medicine (NM) physicians in defining primary and lymph node tumor volumes (GTVp and GTVn) for head and neck cancer (HNC) radiotherapy.

This study includes 30 consecutive HNC patients referred for definitive curative (chemo)-radiotherapy. Imaging data including head and neck MRI, [18F]-FDG-PET and CT scan were evaluated by the MDT. The RO identified the ’undeniable’ tumor as GTVp_core and determined GTVp_max, representing the maximum tumoral volume. The MDT delineation (MDT-D) by RX and NM physicians outlined their respective primary GTVs (GTVp_RX and GTVp_NM). During the MDT meeting (MDT-M), these contours were discussed to reach a consensus on the final primary GTV (GTVp_final). In the comparative analysis of various GTVp delineations, we performed descriptive statistics and assessed two MDT-M factors: 1) the added value of MDT-M, which includes the section of GTVp_final outside GTVp_core but within GTVp_RX or GTVp_NM, and 2) the part of GTVp_final that deviates from GTVp_max, representing the area missed by the RO. For GTVn, discussions evaluated lymph node extent and malignancy, documenting findings and the frequency of disagreements.

The average GTVp core and max volumes were 19.5 cc (range: 0.4–90.1) and 22.1 cc (range: 0.8–106.2), respectively. Compared to GTVp_core, MDT-D to GTVp_final added an average of 3.3 cc (range: 0–25.6) and spared an average of 1.3 cc (0–15.6). Compared to GTVp_max, MDT-D and -M added an average of 2.7 cc (range: 0–20.3) and removed 2.3 cc (0–21.3). The most frequent GTVn discussions included morphologically suspicious nodes not fixing on [18F]-FDG-PET and small [18F]-FDG-PET negative retropharyngeal lymph nodes.

Multidisciplinary review of target contours in HNC is essential for accurate treatment planning, ensuring precise tumor and lymph node delineation, potentially improving local control and reducing toxicity.

Background

Proton therapy (PT) has unique biologic properties with excellent clinical outcomes for the management of localized prostate cancer. Here, we aim to characterize the toxicity of PT for patients with localized prostate cancer and propose mitigation strategies using a large institutional database.

Methods

We reviewed medical records of 2772 patients with localized prostate cancer treated with definitive PT between May 2006 through January 2020. Disease risk was stratified according to National Comprehensive Cancer Network guidelines as low [LR, n = 640]; favorable-intermediate [F-IR, n = 849]; unfavorable-intermediate [U-IR, n = 851]; high [HR, n = 315]; or very high [VHR, n = 117]. Descriptive statistics and Kaplan-Meier estimates assessed toxicity and freedom from biochemical relapse (FFBR).

Results

Median follow-up was 7.0 years. The median dose was 78 Gy(RBE)(range: 72–79.2 Gy) in 2.0 Gy(RBE) fractions; 63 % of patients received 78 Gy(RBE) in 39 fractions, and 29 % received 76 Gy(RBE) in 38 fractions. Overall rates of late grade ≥3 GU and GI toxicity were 0.87 % and 1.01 %, respectively. Two patients developed grade 4 late GU toxicity and seven patients with grade 4 late GI toxicity. All patients experiencing severe late grade 4 toxicities were treated to 78 Gy(RBE) in 39 fractions with 80 Gy(RBE) dose to the anterior rectal wall and/or bladder neck. The 10-year FFBR rates for patients with LR to U-IR disease were compared between those treated with 76 and 78 Gy(RBE); the rates were 94.5 % (95 % confidence interval [CI] 92.4–96.0 %) and 93.2 % (95 % CI 91.3–95.7 %), respectively (log-rank p = 0.22).

Conclusions

Proton therapy is associated with low rates of late grade ≥3 GU and GI toxicity. While rare, late grade 4 toxicities occurred in nine (0.3 %) patients. De-escalation to a total dose of 76 Gy(RBE) yields excellent clinical outcomes for patients with LR to U-IR disease with the potential for significant reductions in grade ≥3 late toxicity.

Purpose

To establish a radiomics model using radiomics features from different region of interests (ROI) based on dosimetry-related regions in enhanced computed tomography (CT) simulated images to predict radiation pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC).

Methods

Our retrospective study was conducted based on a cohort of 236 NSCLC patients (59 of them with RP≥2) who were treated in 2 institutions and divided into the primary cohort (n = 182,46 of them with RP≥2) and external validation cohort (n = 54,13 of them with RP≥2). Radiomic features extracted from three ROIs were defined as the whole lung (WL), the dose volume histogram (DVH) of the lung V20 (V20_Lung) and the DVH of the V30 of lung minus the planning target volume (PTV) (V30 Lung-PTV). A total of 107 radiomics features were extracted from each ROIs. The U test, correlation coefficient and least absolute shrinkage and selection operator (LASSO) were performed for features selection. Six models based on different classification algorithms were developed to select the best radiomics model (R model).In addition, we built a dosimetry model then combined it with the best R model to create a mixed model (R+D model) The receiver operating characteristic (ROC) curve was delineated to assess the predictive efficacy of the models. Decision curve analysis could benefit from the model proposals through the assessment of clinical utility.

Results

Among the three ROIs, the best R model constructed from the LightGBM algorithm demonstrated the strongest discriminative ability in the ROI of V30 Lung-PTV. The corresponding area under the curve (AUC) value was 0.930 (95 % confidence interval (CI): 0.829–0.941). The D model, R model and R+D model achieved AUC values of 0.798 (95 %CI: 0.732–0.865), 0.930 (95 %CI: 0.829–0.941) and 0.940 (95 %CI: 0.906–0.974) in primary cohort, and in external validation cohort, the AUC values were 0.793 (95 %CI:0.637–0.949), 0.887 (95 %CI:0.810–0.993), 0.951 (95CI%:0.891–1.000). Decision curve demonstrate that R+D model could benefit for patients through the assessment of clinical utility.

Conclusion

The radiomics model was able to predict the acute RP more effectively in comparison with the traditional dosimetry model. Especially the radiomics model based on the V30 Lung-PTV region was able to achieve a higher accuracy when compared to the other regions.

Background

In glioblastoma (GBM), tumor progression occurs mainly within the irradiated tumor volume. To address this challenge, a radiosensitization strategy with intravenous gadolinium-based theranostic nanoparticles (AGuIX) is being explored in the NANO-GBM phase1b/2R trial (NCT04881032). Here, we present the results of the phase 1b part, which is the first-in-human use of these nanoparticles with radiotherapy and chemotherapy for the treatment of newly diagnosed GBM.

Material and Methods

Eligible patients were aged 18 to 75 years with newly diagnosed and histologically confirmed GBM, with incomplete resection (biopsy or partial surgery). The phase 1b part was a dose escalation approach (Time-to-event Continuous Reassessment Method) with three dose levels: 50, 75, and 100 mg/kg. Patients were treated with RT (60 Gy), and concomitant and adjuvant TMZ, and 4 injections of AGuIX (D-3/-7, D1, D8, and D15). Dose-limiting-toxicity (DLT) was defined as any grade 3–4 adverse event (CTCAE v5.0), excluding alopecia, nausea, and rapidly controlled vomiting. Pharmacokinetic (PK), and biodistribution based on MRI were evaluated.

Results

Between March 2022 and March 2023, eight patients were enrolled: 1 at 50 mg/kg, 1 at 75 mg/kg, and 6 at 100 mg/kg. All patients received the four AGuIX injections. Only one patient experienced a DLT (at 100 mg/kg): a grade 3 lymphopenia (related to TMZ). The RP2D of AGuIX was determined as 100 mg/kg. AGuIX mean AUC increased with dose. Regions of GBM with moderate (36–123 µM), and high (123–291 µM) or very high (>291 µM) AGuIX concentrations accounted in average for 38.7 and 26.8 %, respectively.

Conclusion

These results confirm the lack of AGuIX-related toxicity and the widespread dispersion of nanoparticles throughout GBM. This supports progression to the randomized phase 2 part, utilizing an RP2D of AGuIX of 100 mg/kg (4 injections).