Clinical and Translational Radiation Oncology最新文献

Background and purpose

Radical surgery is the standard of care for early rectal cancer. However, alternative organ-preserving approaches are attractive, especially in frail or elderly patients as these avoid surgical complications. We have assessed the efficacy of sole Contact X-ray Brachytherapy (CXB) treatment in stage-1 rectal cancer patients who were unsuitable for or declined surgery.

Materials and methods

This retrospective multi-centre study (2009–2021) evaluated 76 patients with T1/2-N0-M0 rectal adenocarcinomas who were treated with CXB alone. Outcomes were assessed for the entire cohort and sub-groups based on the T-stage and the criteria for receiving CXB alone; Group A: patients who were fit enough for surgery but declined, Group B: patients who were high-risk for surgery and Group C: patients who had received prior pelvic radiation for a different cancer.

Results

With a median follow-up of 26(IQR:12–49) months, initial clinical Complete Response (cCR) was 82(70–93)% with rates of local regrowth 18(8–29)%, 3-year actuarial local control (LC) 84(75–95)%, distant relapse 3 %, and no nodal relapse. 5-year disease-free survival (DFS) and overall survival (OS) were 66(48–78)% and 58(44–75)%. Lower OS was observed in Groups B [HR:2.54(95 %CI:1.17, 5.59), p = 0.02] and C [HR:2.75(95 %CI:1.15, 6.58), p = 0.03]. Previous pelvic radiation predicted lower cCR and OS. The main toxicity was G1-2 rectal bleeding (26 %) and symptoms of impaired anal sphincter function were not reported in any patients.

Conclusion

CXB treatment alone achieved a high cCR rate with satisfactory LC and DFS. Inferior oncological outcomes were observed in patients who had received prior pelvic radiotherapy. CXB alone, with its favourable toxicity profile and avoidance of general anaesthesia and surgery risks, therefore, can be considered for patients who are unsuitable for or refuse surgery.

Immunotherapy has revolutionized the field of cancer treatment, changing the standard of care to the use of immune checkpoint inhibitors. Radiotherapy can boost anti-tumour immune responses by changing the tumour microenvironment, but it also can cause radiotherapy-induced lymphopenia (RIL), a decrease in circulating lymphocyte counts. RIL has been associated with lower survival in patients undergoing radiotherapy, and new studies have suggested that it can also affect immunotherapy outcome. To study RIL’s effects and to explore mitigation treatment strategies, preclinical models closely mimicking the clinical situation are needed. State-of-the-art image-guided small animal irradiators now offer the possibility to target specific organs in small animals to induce RIL, aiding research on its molecular mechanisms and prevention. This review covers the relationship between radiotherapy and RIL, its impact on patient survival, and future directions to generate models to investigate and prevent RIL.

Background

Hypoxia-inducible factor-1α (HIF-1α) is a crucial transcription factor activated under hypoxic conditions, known to regulate genes associated with tumor survival, progression, and response to therapy. This study aimed to evaluate the prognostic significance of HIF-1α expression in patients with anal squamous cell carcinoma (ASCC) undergoing chemoradiation therapy.

Methods

We conducted a retrospective analysis of 28 ASCC patients treated with intensity-modulated radiotherapy (IMRT) at our center from 2009 to 2022. HIF-1α expression was assessed via immunohistochemistry on formalin-fixed paraffin-embedded tissue specimens. Quantitative analysis of HIF-1α expression was performed, and its relationship with clinical outcomes, including disease-free survival (DFS), locoregional relapse-free survival (LRRFS), and overall survival (OS), was examined using Cox regression models. Furthermore, ASCC tissue specimens from 17 patients were analyzed for potential PIK3CA mutations using Sanger sequencing.

Results

High HIF-1α expression was significantly associated with poorer DFS (p = 0.005), LRRFS (p = 0.012), and OS (p = 0.009). HIF1α expression was marginally significantly higher in males compared to females (p = 0.056) while there was no significant difference found based on tumor stage or p16 status. However, a positive correlation was identified between BMI and HIF-1α levels (Pearson correlation r = 0.5, p = 0.0084), suggesting a link between metabolic status and tumor hypoxia. Only one patient exhibited a PIK3CA mutation, preventing a reliable assessment of its correlation with HIF-1α expression.

Conclusion

Our findings underscore the importance of HIF-1α as a potential biomarker for predicting survival outcomes in ASCC patients treated with chemoradiation. The association between higher BMI and increased HIF-1α expression may provide insights into the interplay between metabolic health and tumor biology in ASCC. Further studies with larger cohorts are needed to validate these findings and explore targeted therapies focusing on HIF-1α modulation.

Background

High-grade glioma (HGG) patients post-radiotherapy often face challenges distinguishing true tumor progression (TTP) from pseudoprogression (PsP). This study evaluates the effectiveness of systemic inflammatory markers and volume of enhancing tissue on post-contrast T1 weighted (T1WCE) MRI images for this differentiation within the first six months after treatment.

Material and Methods

We conducted a retrospective analysis on a cohort of HGG patients from 2015 to 2021, categorized per WHO 2016 and 2021 criteria. We analyzed treatment responses using modified RANO criteria and conducted volumetry on T1WCE and T2W/FLAIR images.

Blood parameters assessed included neutrophil/lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI). We employed Chi-square, Fisher’s exact test, and Mann-Whitney U test for statistical analyses, using log-transformed predictors due to multicollinearity. A Cox regression analysis assessed the impact of PsP- and TTP-related factors on overall survival (OS).

Results

The cohort consisted of 39 patients, where 16 exhibited PsP and 23 showed TTP. Univariate analysis revealed significantly higher NLR and SII in the TTP group [NLR: 4.1 vs 7.3, p = 0.002; SII 546.5 vs 890.5p = 0.009]. T1WCE volume distinctly differentiated PsP from TTP [2.2 vs 11.7, p < 0.001]. In multivariate regression, significant predictors included NLR and T1WCE volume in the “NLR Model,” and T1WCE volume and SII in the “SII Model.” The study also found a significantly lower OS rate in TTP patients compared to those with PsP [HR 3.97, CI 1.59 to 9.93, p = 0.003].

Conclusion

Elevated both, SII and NLR, and increased T1WCE volume were effective in differentiating TTP from PsP in HGG patients post-radiotherapy. These results suggest the potential utility of incorporating these markers into clinical practice, though further research is necessary to confirm these findings in larger patient cohorts.

Bone metastases (BMs) are the most common cause of cancer-related pain and radiation therapy plays a key role in treating pain caused by it. The half-body irradiation (HBI) is a modality that can be used to treat patients with multiple painful BMs. In the modern era, concerns about toxicity and the availability of new agents requiring robust bone marrow function have limited the use of HBI in advanced cancer. Concerns about HBI toxicity stem from outdated techniques; modern methods like volumetric modulated arc therapy (VMAT) and helical tomotherapy now allow safer irradiation of complex target volumes. We conducted a systematic review to present updated information about HBI efficacy and potential toxicity. Pain relief usually occurs very quickly 2–3 weeks after HBI. The overall pain response rate was high in all the series, accounting for a median of 84 % (75.6–89 %), with a median of 36 % complete pain response. The toxicity is usually limited to G1/G2, with very rare G3 cases. More than 50 % of patients can reduce analgesic intake after HBI. Additionally, with modern radiotherapy techniques, quality of life is improved in most patients. HBI is a safe and effective method and should once again be reconsidered for more frequent use.

Objective

The present study aimed to compare the diagnostic value of gallium-68-labeled fibroblast activation protein inhibitor positron emission tomography/computed tomography (⁶⁸Ga-FAPI PET/CT) and fluorine-18-labeled fluorodeoxyglucose PET/CT (¹⁸F-FDG PET/CT) for detecting recurrent colorectal cancers (CRCs).

Materials and Methods

Fifty-six patients (age: 18–80 years, 31 men and 25 women) with suspected recurrent CRC were enrolled and underwent ¹⁸F-FDG PET/CT and ⁶⁸Ga-FAPI PET/CT sequentially within 1 week. The maximum standard uptake value (SUVmax), tumor-to-background ratio (TBR), and diagnostic accuracy were estimated and compared between the two modalities by using Student’s t-test. The Wilcoxon signed-rank test was used to compare peritoneal carcinoma index (PCI) scores between the two imaging modalities.

Results

⁶⁸Ga-FAPI PET/CT showed higher sensitivity for detecting recurrence (93 % vs. 79 %); lymph node metastasis (89 % vs. 78 %), particularly peritoneal lymph node metastasis (92 % vs. 63 %); and metastatic implantation on the intestinal wall (100 % vs. 25 %) compared to ¹⁸F-FDG PET/CT. However, ⁶⁸Ga-FAPI PET/CT showed lower sensitivity for detecting bone metastasis (67 % vs. 100 %). The mean SUVmax values of peritoneal metastases and metastatic implantation on the intestinal wall were 4.28 ± 2.70 and 7.58 ± 1.66 for ¹⁸F-FDG PET/CT and 5.66 ± 1.97 and 6.70 ± 0.25 for ⁶⁸Ga-FAPI PET/CT, respectively. Furthermore, ⁶⁸Ga-FAPI PET/CT showed significantly higher TBR for peritoneal metastatic lesions (4.22 ± 1.47 vs. 1.41 ± 0.89, p < 0.0001) and metastatic implantation on the intestinal wall (5.63 ± 1.24 vs. 2.20 ± 0.5, p = 0.02) compared to ¹⁸F-FDG PET/CT. For the same patient, ⁶⁸Ga-FAPI PET/CT yielded a more accurate PCI score and a greater area under the curve value for the receiver operating characteristic curve (p < 0.01) than ¹⁸F-FDG PET/CT.

Conclusion

⁶⁸Ga-FAPI PET/CT was superior to ¹⁸F-FDG PET/CT for detecting recurrence and peritoneal metastases. Hence, we propose the combination of these two modalities for better clinical diagnosis and management of patients with CRC.

Purpose/objectives

The indications, techniques, and extent to which proton beam therapy (PBT) is employed for breast cancer are unknown. We seek to determine PBT utilization for breast cancer.

Materials/methods

The Particle Therapy Co-Operative Group (PTCOG) Breast Subcommittee developed an IRB-approved 29-question survey and sent it to breast cancer radiation oncologists at all active PBT centers worldwide in June 2023. Descriptive statistics were used to summarize responses, and comparisons by continent were performed using Fisher’s exact tests.

Results

Of 79 surveys distributed, 28 recipients submitted responses (35 % response rate) representing fifteen U.S., 8 European, and 5 Asian centers (continent response rate 50 %, 38 %, and 18 %, respectively). Overall, 93 % reported treating breast cancer patients with PBT; 13 (50 %) have treated ≥100 breast cancer patients at their center since opening. Most (89 %) have pencil beam scanning technology. Nearly half (46 %) use moderate hypofractionation (15–20 fractions) for regional nodal irradiation and 42 % conventional fractionation (25–30 fractions). More European centers prefer hypofractionation (88 %) vs. Asian (50 %) and U.S. (21 %) centers (p = 0.003). Common patient selection methods were practitioner determination/patient preference (n = 16) and comparative plan evaluation (n = 15). U.S. centers reported the most experience with breast PBT, with 71 % having treated ≥100 breast cancer patients vs. 38 % in Europe and none in Asia (p = 0.001). Of respondent centers, 39 % enrolled ≥75 % of breast PBT patients on a research study.

Conclusion

Utilization, patient selection methods, and dose-fractionation approaches for breast cancer PBT vary worldwide. These survey data serve as a benchmark from which successor surveys can provide insight on practice pattern evolution.

Background

The benefit of prophylactic whole pelvis radiation therapy (WPRT) in prostate cancer has been debated for decades, with evidence based mainly on conventional fractionation targeting pelvic nodes.

Aim

This retrospective cohort study aimed to explore the impact of adding moderately hypofractionated pelvic radiotherapy to prostate-only irradiation (PORT) on prognosis, toxicity, and quality of life in real-world settings.

Materials and methods

Patients with high-risk and conventionally staged prostate cancer (cT1-3N0M0) treated with moderately hypofractionated WPRT or PORT, using external beam radiotherapy alone or combined with high-dose-rate brachytherapy, at Örebro University Hospital between 2008 and 2021 were identified. Biochemical failure-free survival (BFFS), metastasis-free survival (MFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were compared using Kaplan-Meier method and Cox proportional hazards. Toxicity and quality of life measures were also analysed.

Results

Among 516 patients (227 PORT, 289 WPRT), 5-year BFFS rates were 77 % (PORT) and 74 % (WPRT), adjusted HR=1.50 (95 % CI=0.88–2.55). No significant differences were found in MFS, PCSS, or OS in main analyses. WPRT was associated with a higher risk of acute grade ≥ 2 and 3 genitourinary toxicities whereas no differences in late toxicities or quality of life between PORT and WPRT were observed.

Conclusion

We found no significant differences in oncological outcomes or quality of life when comparing moderately hypofractionated PORT to WPRT. Some differences in toxicity patterns were observed. Despite caveats related to study design, our findings support the need for further research on WPRT’s impact on treatment-related and patient-reported outcomes.