Advances in Radiotherapy and Prognosis

Aim: The gold standard of care for pancreatic adenocarcinoma is the integrated treatment of surgery and chemotherapy (ChT), but about 50% of patients present with unresectable disease. Our study evaluated the efficacy in terms of local control, survival and safety of stereotactic body radiation therapy (SBRT) in locally advanced pancreatic cancer (LAPC). Methods: A retrospective study (STEP study) analyzed patients with LAPC treated with a dose of 45 Gy in 6 fractions. Local control (LC), distant progression free survival (DPFS), overall survival (OS) and toxicity were analyzed according to the Kaplan-Meier method. Results: A total of 142 patients were evaluated. Seventy-six patients (53.5%) received induction ChT before SBRT. The median follow-up was 11 months. One-, 2- and 3-year LC rate was 81.9%, 69.1% and 58.5%. Median DPFS was 6.03 months; 1- and 2-year DPFS rate was 19.9% and 4.5%. Median OS was 11.6 months and 1-, 2- and 3-year OS rates were 45.4%, 16.1%, and 9.8%. At univariate analysis, performed by the log-rank test, age < 70 years (p = 0.037), pre-SBRT ChT (p = 0.004) and post-SBRT ChT (p = 0.019) were associated with better OS. No patients experienced G3 toxicity. Conclusion: SBRT represents an effective and safe therapeutic option in the multimodal treatment of patients with LAPC in terms of increased LC. When SBRT was sequentially integrated with ChT, the treatment proved to be promising in terms of OS as well. Full article

Background: Patients with brain, head, and neck tumors experience a decline in their quality of life due to radiation retinopathy and optic neuropathy. Little is known about the dose–response relationship and patient characteristics. We aimed to systematically review the prevalence of radiation retinopathy and optic neuropathy. Method: The primary outcome was the pooled prevalence of radiation retinopathy and optic neuropathy. The secondary outcome included the effect of the total radiation dose prescribed for the tumor according to the patient’s characteristics. Furthermore, we aimed to evaluate the radiation dose parameters for organs at risk of radiation retinopathy and optic neuropathy. Results: The pooled prevalence was 3.8%. No retinopathy was reported for the tumor’s prescribed dose of <50 Gy. Optic neuropathy was more prevalent for a prescribed dose of >50 Gy than <50 Gy. We observed a higher prevalence rate for retinopathy (6.0%) than optic neuropathy (2.0%). Insufficient data on the dose for organs at risk were reported. Conclusion: The prevalence of radiation retinopathy was higher compared to optic neuropathy. This review emphasizes the need for future studies considering retinopathy and optic neuropathy as primary objective parameters. Full article

Background: Radiotherapy is essential in the management of head–neck cancer. During the course of radiotherapy, patients may develop significant anatomical changes. Re-planning with adaptive radiotherapy may ensure adequate dose coverage and sparing of organs at risk. We investigated the consequences of adaptive radiotherapy on head–neck cancer patients treated with volumetric-modulated arc radiation therapy compared to simulated non-adaptive plans: Materials and methods: We included in this retrospective dosimetric analysis 56 patients treated with adaptive radiotherapy. The primary aim of the study was to analyze the dosimetric differences with and without an adaptive approach for targets and organs at risk, particularly the spinal cord, parotid glands, oral cavity and larynx. The original plan (OPLAN) was compared to the adaptive plan (APLAN) and to a simulated non-adaptive dosimetric plan (DPLAN). Results: The non-adaptive DPLAN, when compared to OPLAN, showed an increased dose to all organs at risk. Spinal cord D2 increased from 27.91 (21.06–31.76) Gy to 31.39 (27.66–38.79) Gy (p = 0.00). V15, V30 and V45 of the DPLAN vs. the OPLAN increased by 20.6% (p = 0.00), 14.78% (p = 0.00) and 15.55% (p = 0.00) for right parotid; and 16.25% (p = 0.00), 18.7% (p = 0.00) and 20.19% (p = 0.00) for left parotid. A difference of 36.95% was observed in the oral cavity V40 (p = 0.00). Dose coverage was significantly reduced for both CTV (97.90% vs. 99.96%; p = 0.00) and PTV (94.70% vs. 98.72%; p = 0.00). The APLAN compared to the OPLAN had similar values for all organs at risk. Conclusions: The adaptive strategy with re-planning is able to avoid an increase in dose to organs at risk and better target coverage in head–neck cancer patients, with potential benefits in terms of side effects and disease control. Full article

Hematopoietic injury resulting from the damage of hematopoietic stem/progenitor cells (HSPCs) can be induced by either nuclear accident or radiotherapy. Radiomitigation of HSPCs is critical for the development of medical countermeasure agents. StemRegenin 1 (SR1) modulates the maintenance and function of HSPCs under non-stress conditions. However, the impact of SR1 in radiation-induced hematopoietic injury both in vivo and in vitro remains unknown. In this study, we found that treatment with SR1 after irradiation of C57BL/6 mice significantly mitigates TBI-induced death (80% of SR1-treated mice survival vs. 30% of saline-treated mice survival) with enhanced recovery of peripheral blood cell counts, with the density and cell proliferation of bone marrow components as observed by Hematoxylin and Eosin (H&E) and Ki-67 staining. Interestingly, in vitro analysis of human HSPCs showed that SR1 enhanced the population of human HSPCs (CD34+) under both non-irradiating and irradiating conditions, and reduced radiation-induced DNA damage and apoptosis. Furthermore, SR1 attenuated the radiation-induced expression of a member of the pro-apoptotic BCL-2 family and activity of caspase-3. Overall, these results suggested that SR1 modulates the radioresponse of HSPCs and might provide a potential radiomitigator of hematopoietic injury, which contributes to increase the survival of patients upon irradiation. Full article

This article describes the methodology used and provides a characterization of the study population in CANTO-RT (CANcer TOxicities RadioTherapy). CANTO (NCT01993498) is a prospective clinical cohort study including patients with stage I-III BC from 26 French cancer centers. Patients matching all CANTO inclusion and exclusion criteria who received RT in one of the 10 top recruiting CANTO centers were selected. Individual full DICOM RT files were collected, pseudo-anonymized, structured and analyzed on the CANTO-RT/UNITRAD web platform. CANTO-RT included 3875 BC patients with a median follow-up of 64 months. Among the 3797 patients with unilateral RT, 3065 (80.4%) had breast-conserving surgery, and 2712 (71.5%) had sentinel node surgery. Tumor bed boost was delivered in 2658 patients (68.5%) and lymph node RT in 1356 patients (35%), including internal mammary chain in 844 patients (21.8%). Most patients (3691 (95.3%)) were treated with 3D conformal RT. Target volumes, organs at risk contours and dose/volume histograms were extracted after quality-control procedures. CANTO-RT is one of the largest early BC prospective cohorts with full individual clinical, biological, imaging and DICOM RT data available. It is a valuable resource for the identification and validation of clinical and dosimetric predictive factors of RT and multimodal treatment-related toxicities. Full article

Purpose: To determine the safety and outcome profile of five-fraction stereotactic radiotherapy (FSRT) for brain metastases (BM), either as a definitive or adjuvant treatment. Methods: We assessed clinical data of patients receiving five fractions of 7 Gy each (cumulative physical dose of 35 Gy) to BM or surgical cavities. The primary endpoints were toxicity and radiation necrosis (RN) rates. Secondary endpoints were 1-year cumulative local control rate (LCR) and estimated overall survival (OS). Results: A total of 36 eligible patients receiving FSRT to a total of 49 targets were identified and included. The median follow up was 9 (1.1–56.2) months. The median age was 64.5 (34–92) years, the median ECOG score was 1, and the median Diagnostic-Specific Graded Prognostic Assessment (DS-GPA) score was 2. Treatment was well tolerated and there were no grade 3 adverse events or higher. The overall RN rate was 14.3% and the median time to RN was 12.9 (1.8–23.8) months. RN occurrence was associated with immunotherapy, young age (≤45 years), and large PTV. The cumulative 1-year local control rate was 83.1% and the estimated median local progression free-survival was 18.8 months. The estimated median overall survival was 11 (1.1–56.2) months and significantly superior in those patients presenting with RN. Conclusions: FSRT with 5 × 7 Gy represents a feasible, safe, and efficient fast track approach of intensified FSRT with acceptable LC and comparable RN rates for both the adjuvant and definitive RT settings. Full article

Background: Significant changes in the accessibility and viability of health services have been observed during the COVID-19 period, particularly in vulnerable groups such as cancer patients. In this study, we described the impact of radical practice and perceived changes on cancer patients’ mental well-being and investigated potential outcome descriptors. Methods: Generalized anxiety disorder assessment (GAD-7), patient health (PHQ-9), and World Health Organization-five well-being index (WHO-5) questionnaires were used to assess anxiety, depression, and mental well-being. Information on participants, disease baseline information, and COVID-19-related questions were collected, and related explanatory variables were included for statistical analysis. Results: The mean score values for anxiety, depression, and mental well-being were 4.7 ± 5.53, 4.9 ± 6.42, and 72.2 ± 18.53, respectively. GAD-7 and PHQ-9 scores were statistically associated (p < 0.001), while high values of GAD-7 and PHQ-9 questionnaires were related to low values of WHO-5 (p < 0.001).Using the GAD-7 scale, 16.2% of participants were classified as having mild anxiety (GAD-7 score: 5–9).Mild to more severe anxiety was significantly associated with a history of mental health conditions (p = 0.01, OR = 3.74, 95% CI [1.372–10.21]), and stage category (stage III/IV vs. I/II, p = 0.01, OR = 3.83, 95% CI [1.38–10.64]. From the participants, 36.2% were considered to have depression (PHQ-9 score ≥ 5). Depression was related with older patients (p = 0.05, OR = 1.63, 95% CI [1.16–2.3]), those with previous mental health conditions (p = 0.03, OR = 14.24, 95% CI [2.47–81.84]), those concerned about the COVID-19 impact on their cancer treatment (p = 0.027, OR = 0.19, 95% CI [0.045–0.82]) or those who felt that COVID-19 pandemic has affected mental health (p = 0.013, OR = 3.56, 95% CI [1.30–9.72]). Additionally, most participants (86.7%) had a good well-being score (WHO-5 score ≥ 50). Mental well-being seemed more reduced among stage I–III patients than stage IV patients (p = 0.014, OR = 0.12, 95% CI [0.023–0.65]). Conclusion: There is a necessity for comprehensive cancer care improvement. These patients’ main concern related to cancer therapy, yet the group of patients who were mentally affected by the pandemic should be identified and supported. Full article

The optimal thoracic radiotherapy (TRT) dose and fractionation for limited-stage small cell lung cancer (LS-SCLC) using modern techniques remain unclear. We conducted systematic review and meta-analyses of the efficacy and safety differences between definitive hypofractionated TRT (HypoTRT), conventional TRT (ConvTRT) and hyperfractionated TRT (HyperTRT), especially in the modern era. Eligible randomized controlled trials (RCTs), real-world cohorts, and single-arm trials published between 1990 and 2021 were identified. Two meta-analyses of overall survival (OS) were conducted: (i) a random-effects meta-analysis based on reconstructed individual-patient data (IPD) of all studies; and (ii) a Bayesian network meta-analysis based on study-level aggregated data (AD) of RCTs. The incidences of severe radiation-related toxicities were compared using the random-effects meta-regression model. Overall, 53 of the 30,031 publications met the inclusion criteria, and a total of 8006 IPD were reconstructed. After adjusting for key treatment variables and stratification by study type, there were no significant differences in the OS rates between the altered fractionation regimens (HypoTRT vs. HyperTRT, aHR [adjusted HR] = 1.05, 95% CI 0.93–1.19; ConvTRT vs. HyperTRT, aHR = 1.00, 95% CI 0·90–1.11; HypoTRT vs. ConvTRT, aHR = 1.05, 95% CI 0.91–1.20). In the modern era, the survival outcomes of all three schedules, while remaining comparable, have improved significantly. Results of the AD-based network meta-analysis were consistent with those of IPD analysis, and HypoTRT was ranked as the best regimen (SUCRA = 81%). There were no significant differences in toxicities between groups when using modern radiation techniques. In the modern era, no significant differences in OS or severe radiation-related toxicities were observed between altered schedules in LS-SCLC. HypoTRT may be associated with moderate and non-significant OS improvements, which should be further confirmed in prospective randomized phase III trials. Full article

Radioembolization (RE) is a viable therapy option in patients with intrahepatic cholangiocarcinoma (ICC). This study delineates a prognostic score regarding overall survival (OS) after RE using routine pre-therapeutic parameters. A retrospective analysis of 39 patients (median age, 61 [range, 32–82] years; 26 females, 13 males) with ICC and 42 RE procedures was conducted. Cox regression for OS included age, ECOG, hepatic and extrahepatic tumor burden, thrombosis of the portal vein, ascites, laboratory parameters and dose reduction due to hepatopulmonary shunt. Median OS after RE was 8.0 months. Using univariable Cox, ECOG ≥ 1 (hazard ratio [HR], 3.8), AST/ALT quotient (HR, 1.86), high GGT (HR, 1.002), high CA19-9 (HR, 1.00) and dose reduction of 40% (HR, 3.8) predicted shorter OS (each p < 0.05). High albumin predicted longer OS (HR, 0.927; p = 0.045). Multivariable Cox confirmed GGT ≥ 750 [U/L] (HR, 7.84; p < 0.001), ECOG > 1 (HR, 3.76; p = 0.021), albumin ≤ 41.1 [g/L] (HR, 3.02; p = 0.006) as a three-point pre-therapeutic prognostic score. More specifically, median OS decreased from 15.3 months (0 risk factors) to 7.6 months (1 factor) or 1.8 months (≥2 factors; p < 0.001). The proposed score may aid in improved pre-therapeutic patient identification with (un-)favorable OS after RE and facilitate the balance between potential life prolongation and overaggressive patient selection. Full article

Background: While radiotherapy has been studied in the treatment of locally advanced pancreatic ductal adenocarcinoma (PDAC), few studies have analyzed the effects of radiotherapy on PDAC in patients with liver metastases. This study aimed to determine whether PDAC patients with liver metastases have improved survival after radiotherapy treatment. Methods: The data of 8535 patients who were diagnosed with PDAC with liver metastases between 2010 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Survival analysis and Cox proportional hazards regression analysis of cancer-specific mortality and overall survival were performed, and propensity score matching (PSM) was used to reduce selection bias. Results: After PSM, the median overall survival (mOS) and median cancer-specific survival (mCSS) in the radiotherapy group were longer than those in the nonradiotherapy group (OS: 6 months vs. 4 months; mCSS: 6 months vs. 5 months, both p < 0.05), respectively. The multivariate analysis showed that cancer-specific mortality rates were higher in the nonradiotherapy group than in the radiotherapy group (HR: 1.174, 95% CI: 1.035–1.333, p = 0.013). The Cox regression analysis according to subgroups showed that the survival benefits (OS and CSS) of radiotherapy were more significant in patients with tumor sizes greater than 4 cm (both p < 0.05). Conclusions: PDAC patients with liver metastases, particularly those with tumor sizes greater than 4 cm, have improved cancer-specific survival (CSS) rates after receiving radiotherapy. Full article

The main objective of this prospective observational study was the characterization of the feasibility and early outcome of image-guided (IG) volumetric modulated arc (VMAT) radiosurgery (SRS) followed by resection for patients with large intraocular melanoma. Our study included consecutive patients with unfavorable-risk melanoma, enrolled in an ophthalmic oncology center. IG-VMAT-SRS was applied by high-resolution 4D image guidance and monitoring. Current stereotactic technique parameters were evaluated for comparison. Side effects and eye function, based on a 5-point CTC assessment score, were quantified. In patients with tumors located more than 0.7–1 mm apart from the optic nerve, partial to complete volume-sparing of the optic nerve head could be achieved. In 95.5% of this subgroup, the vitality of the optic nerve and vision could be preserved by the multimodality-treatment approach (mean follow-up: 18 months (7.5–36 months)). The advanced technology of stereotactic radiotherapy demonstrated the achievability of steep dose gradients around the high-dose volume, with 4D-IG-VMAT dose application. These results enforce IG-VMAT-SRS followed by resection as one of the major therapeutic options for patients with large intraocular melanoma. The combination of 4D-IG high-precision SRS and resection provides an effective treatment for large intraocular melanoma, with few side effects, and enables an eye bulb and even vision preserving modus operandi. Full article

Background: The safe use of radiotherapy (RT) requires compliance with dose/volume constraints (DVCs) for organs at risk (OaRs). However, the available recommendations are sometimes conflicting and scattered across a number of different documents. Therefore, the aim of this work is to provide, in a single document, practical indications on DVCs for OaRs in external beam RT available in the literature. Material and Methods: A multidisciplinary team collected bibliographic information on the anatomical definition of OaRs, on the imaging methods needed for their definition, and on DVCs in general and in specific settings (curative RT of Hodgkin’s lymphomas, postoperative RT of breast tumors, curative RT of pediatric cancers, stereotactic ablative RT of ventricular arrythmia). The information provided in terms of DVCs was graded based on levels of evidence. Results: Over 650 papers/documents/websites were examined. The search results, together with the levels of evidence, are presented in tabular form. Conclusions: A working tool, based on collected guidelines on DVCs in different settings, is provided to help in daily clinical practice of RT departments. This could be a first step for further optimizations. Full article

(1) Background: To investigate the contralateral neck failure (cRF) rates and outcomes among patients with well-lateralized locally advanced oral cavity squamous cell carcinoma (OSCC) with/without ipsilateral or bilateral neck adjuvant irradiation. (2) Methods: Patients with lateralized OSCC diagnosed between 2007 and 2017 were retrospectively enrolled. Patients who had undergone curative surgery with pathologically proven pT3/4 or pN0-2b without distant metastasis were included, while those with cross-midline, neck-level 1a involvement and positive extra-nodal extension (ENE) were excluded. The primary endpoint was the cumulative incidence of 5-year cRF as the first site of failure. The secondary endpoints included cancer-specific survival (CSS), local-regional recurrence-free survival (LRRFS), distant-metastasis-free survival (DMFS), and contralateral-regional recurrence-free survival (cRRFS). (3) Results: In total, 149 patients were analyzed with a median follow-up time of 5.2 years (range, 2.91–7.83). Pathological stages T3 and T4 were 22.7% and 56.8%, respectively. Pathologically negative and positive lymph nodes were 61.4% and 38.6%, respectively. The cumulative 5-year cRF rate was 3.6% (95% CI, 1.3–7.7%). No significant differences in the 5-year CSS, LRRFS, DMFS, and cRRFS were observed among those undergoing unilateral or bilateral neck irradiation. Five patients (3.4%) had contralateral neck recurrence, all simultaneously with local recurrence. No isolated contralateral neck recurrence was identified. (4) Conclusions: The cRF rate was acceptably low in patients with well-lateralized advanced OSCC with the initially uninvolved contralateral neck. Omitting contralateral neck irradiation with active surveillance could be considered without compromising the cure rate in locally advanced OSCC patients. Full article