Radiotherapy Response Research Articles

Application of Artificial Intelligence in Lung Cancer.

Simple SummaryLung cancer is the leading cause of malignancy-related mortality worldwide. AI has the potential to help to treat lung cancer from detection, diagnosis and decision making to prognosis prediction. AI could reduce the labor work of LDCT, CXR, and pathology slides reading. AI as a second reader in LDCT and CXR reading reduces the effort of radiologists and increases the accuracy of nodule detection. Introducing AI to WSI in digital pathology increases the Kappa value of the pathologist and help to predict molecular phenotypes with radiomics and H&E staining. By extracting radiomics from image data and WSI from the histopathology field, clinicians could use AI to predict tumor properties such as gene mutation and PD-L1 expression. Furthermore, AI could help clinicians in decision-making by predicting treatment response, side effects, and prognosis prediction in medical treatment, surgery, and radiotherapy. Integrating AI in the future clinical workflow would be promising.Lung cancer is the leading cause of malignancy-related mortality worldwide due to its heterogeneous features and diagnosis at a late stage. Artificial intelligence (AI) is good at handling a large volume of computational and repeated labor work and is suitable for assisting doctors in analyzing image-dominant diseases like lung cancer. Scientists have shown long-standing efforts to apply AI in lung cancer screening via CXR and chest CT since the 1960s. Several grand challenges were held to find the best AI model. Currently, the FDA have approved several AI programs in CXR and chest CT reading, which enables AI systems to take part in lung cancer detection. Following the success of AI application in the radiology field, AI was applied to digitalized whole slide imaging (WSI) annotation. Integrating with more information, like demographics and clinical data, the AI systems could play a role in decision-making by classifying EGFR mutations and PD-L1 expression. AI systems also help clinicians to estimate the patient’s prognosis by predicting drug response, the tumor recurrence rate after surgery, radiotherapy response, and side effects. Though there are still some obstacles, deploying AI systems in the clinical workflow is vital for the foreseeable future.

Response-Adapted Treatment Following Radiotherapy in Patients With Resectable Locally Advanced Hypopharyngeal Carcinoma

Laryngeal preservation strategies for resectable locally advanced hypopharyngeal carcinoma (LAHPC) have been explored. However, the optimal strategy remains unclear. To evaluate a response-adapted strategy based on an early response to radiotherapy (RT) in patients with resectable LAHPC. This cohort study was conducted from May 2009 to October 2019 with a median (IQR) follow-up period of 66.5 (44.7-97.0) months. The study was conducted at a tertiary academic medical center and included 423 patients pathologically confirmed stage III and IVB LAHPC. A total of 250 patients with previous cancer history, synchronous primary cancer, stage I or II, or with unresectable hypopharyngeal carcinoma were excluded. Patients who reached 80% or greater tumor regression when evaluated endoscopically and by imaging methods at 50 Gy received definitive RT or concurrent chemoradiotherapy, and those with less than 80% regression underwent surgery 4 to 6 weeks after RT. Five-year overall survival and survival with a functional larynx. Overall, 423 patients were included in the study (median [IQR] age, 55 [50-63] years; 408 [96.5%] men and 15 [3.5%] women). The response-adapted and primary surgery groups had significantly better survival than the primary RT group (52.7% and 54.4% vs 27.7%, respectively; P < .001). The response-adapted and primary surgery groups had similar 5-year overall survival of 52.7% vs 54.4%, respectively (hazard ratio [HR], 1.02; 95% CI, 0.75 to 1.39; P = .89). The response-adapted group had better 5-year survival with functional larynx than the primary surgery group (40.6% vs 33.9%; HR, 0.64; 95% CI, 0.49 to 0.84, P = .001). Surgery complications did not significantly differ between the 2 groups. Among patients in the response-adapted group who required total laryngectomy (n = 186) as indicated by pretreatment evaluation, the 5-year cumulative Kaplan-Meier survival with functional larynx was 39.8%. In this cohort study, the response-adapted strategy based on an early RT response facilitated better treatment tailoring, maximum tumor control, and higher laryngeal preservation compared with primary surgery and primary RT strategies. This approach could provide a feasible laryngeal preservation strategy in patients with LAHPC.

Abstract P3-19-04: Minimal increases in tumor infiltrating lymphocytes despite excellent tumor responses after pre-operative accelerated partial breast irradiation in early stage ER+ breast cancer patients

Abstract Purpose/Objectives: Local immune activity as measured by tumor infiltrating lymphocytes (TILs) has been correlated with improved outcomes in triple negative breast cancer (TNBC) and HER2+ disease. Furthermore, increased TILs after pre-operative systemic therapy for TNBC are also correlated with improved outcomes. However, the role of TILs in predicting outcomes in ER/PR+ breast cancer is less well-established. Radiation therapy (RT) can enhance immune cell infiltration in various tumors. However, breast cancer RT is typically given post-operatively, limiting the ability to determine whether RT enhances the %TILs in breast tumors. Here we report %TILs and tumor responses after pre-operative accelerated partial breast irradiation (APBI) as part of a clinical trial to determine whether RT enhances %TILs and whether this correlates with RT response. Materials/Methods: A breast pathologist assessed blindly the % stromal TILs and % tumor cellularity in biopsy and post-RT surgical specimens for patients treated on an in-house pre-operative APBI trial in patients with ER/PR+ breast cancer (NCT02728076). Patients received APBI to 30 Gy in 5 fractions on non-consecutive days, followed by surgery after no less than 5 weeks. Correlation between %TILs and pathologic response was assessed. Results: Thirty-five patients were enrolled and completed treatment. Median age was 65 (50-80). All patients were clinically node-negative and ER/PR+; one was HER2+. Median MRI tumor size was 0.9 cm (0.4-2.1 cm); 54% were grade 2 and 46% grade 1. 23/35 patients had 21- or 70-gene recurrence scores (RS), with 1 high RS; 2 patients received adjuvant chemotherapy and 33/35 received endocrine therapy after surgery. Most patients demonstrated robust tumor responses to RT, with 16/35 (46%) having &amp;lt5% cellularity after RT. With a median cellularity at diagnosis of 40%, 27/35 (77%) had a &amp;gt;20% decrease in cellularity, with only 3 patients having no decrease (range 0-59%). All tumors had low levels of TILs (median 5%, range 1-20%). There was minimal change in %TILs from biopsy to surgery, with 10/35 (28%) patients having increase of TILs &amp;gt4%, 2/35 with an increase of 10%, 2/35 having a decrease of 10% and the remainder with no %TIL increase. There were no correlations between %TILs (at diagnosis or post-RT) and tumor response to RT or RS. Conclusions: Pre-operative APBI in ER/PR+ breast cancers did not significantly increase the %TILs after 5 weeks, despite leading to significant tumor responses as measured by % cellularity. Low %TILs were seen, with no more than a 10% TIL increase after RT. These findings suggest this RT dose and fractionation schedule causes only mild immune changes, as measured by TILs, in this mostly favorable cohort of ER/PR+ cancers. Alternatively, the timing of surgery may have missed maximum TIL levels. Further characterization of TILs along with further studies in similar cohorts and in other breast cancer subtypes are warranted and will be performed to examine the role of pre-operative RT on breast cancer immune responses. Citation Format: Adam Currey, Julie M Jorns, Nina Desai, Tracy R Kelly, Joseph Bovi, Amanda L Kong, Anubha Wadhwa, Eric Paulson, Carmen Bergom. Minimal increases in tumor infiltrating lymphocytes despite excellent tumor responses after pre-operative accelerated partial breast irradiation in early stage ER+ breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-04.

A systematic approach introduced novel targets in rectal cancer by considering miRNA/mRNA interactions in response toradiotherapy.

The discovery of miRNA/mRNA interactions in several biological samples prompted the researchers to explore new biomarkers in tumors. We aimed to investigate the interactions of miRNA/mRNA in response to radiotherapy in the plasma samples of rectal cancer patients. Five microarray datasets related to cancerous and non-cancerous individuals were first used to construct networks. The databases of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were applied to analyze pathway enrichment. The plasma samples were then collected from 55 patients with recently diagnosed rectal cancer and 10 healthy subjects. For radiotherapy courses, the patients have consecutively received 30 sessions of local radiation for six weeks. At last, the expression of selected genes and miRNAs was experimentally measured before and after radiotherapy by qPCR, and the protein levels of the target genes were measured by ELISA assay. We evaluated the therapeutic responses based on the tumor regression grade of the Dworak classification. We identified 5 up-regulated and 5 down-regulated miRNAs and 8 up-regulated and 3 down-regulated genes of the databases. There was a significant increase in tumor suppressor miRNAs, including miR-101-3p, miR-145-5p, miR-26a-5p, miR-34a-5p, and a significant decrease in oncomiRs, including miR-221-3p and miR-17-5p, after radiotherapy compared to the pre-treatment. Moreover, the up-regulated miR-17-5p and miR-221-5p and the down-regulated miR-101-3p and miR-145-5p were directly related to rectal cancer through the interaction with the Wnt, RAS, PI3K, and TGF-β signaling pathways. An analysis of receiver operating characteristics showed that miRNAs 221, 17, and 23 were response-related in locally advanced rectal cancer patients. It seems that monitoring the miRNA/mRNA interactions during radiotherapy can be an appropriate diagnostic tool to track the recovery process and respond to standard therapies.

ALDH1B1 predicts poor survival for locally advanced nasopharyngeal carcinoma patients.

BackgroundDistant metastasis and local recurrence remain the major reasons of treatment failure in locally advanced nasopharyngeal carcinoma (NPC). Therefore, exploring novel biomarkers for prognosis and sensitivity of radiotherapy in locally advanced NPC is crucial. This retrospective study evaluates the expression and prognostic value of aldehyde dehydrogenase 1B1 (ALDH1B1) for locally advanced NPC patients.MethodsSixty-seven locally advanced NPC patients and 22 chronic nasopharyngitis patients between September 2012 to November 2016 at The First Affiliated Hospital of University of South China were enrolled in this study. The expression of ALDH1B1 in tumor tissues were detected by using immunohistochemistry (IHC).ResultsSignificant difference was observed between NPC groups and Pharyngitis tissues groups, and NPC groups has a higher ratio of high ALDH1B1 expression. ALDH1B1 expression were significantly associated with age and radiotherapy response. The Kaplan-Meier analysis indicated that patients with high ALDH1B1 expression had a poor prognosis both in overall survival (OS) and progression-free survival (PFS). Univariate analysis found that age, radiotherapy response and ALDH1B1 expression were correlated with OS. Besides, factors affecting PFS are radiotherapy response and ALDH1B1 expression. Multivariate analysis revealed that radiotherapy response and ALDH1B1 expression were the independent prognostic factors for OS, whereas radiotherapy response was for PFS.ConclusionsThe expression of ALDH1B1 was correlated with age and radiotherapy response. Patients with high ALDH1B1 expression show a poor prognosis both in OS and DFS. ALDH1B1 expression were the independent prognostic factors for OS.

Evaluation of efficacy and tolerance of radical radiotherapy and radiochemotherapy in treatment of locally advanced, unresectable rectal cancer.

133 Background: Evaluation of tolerance and efficacy of two schemes of neoadjuvant treatment in patients with unresectable rectal cancer: radiochemotherapy and radiotherapy, including conventional and accelerated hyperfractionation. Methods: 145 patients (pts) with unresectable, locally advanced rectal cancer. Schemes used: radiotherapy (RT) in 73 (50%) or radiochemotherapy (CRT) in 72 (50%). In RT group conventional fractionation (CFRT) and hyperfractionated accelerated radiotherapy (HART). In CRT 54 Gy in 1.8 Gy fractions was given with two cycles of 5 Fu-LV chemotherapy in three or five day cycles. Results: Objective response (OR) in RT and CRT group was 60% versus 75%. Resection rate (RR) in RT and CRT: 37% versus 65%. Tumor mobility and laparotomy-based unresectability were significant factors for OR. Performance status, tumor mobility, neoadjuvant treatment method were significant for RR. Five-year LC in CRT versus RT: 68% versus 37%. Five-year OS: 52% versus 27%. CRT was independent positive prognostic factor for resection rate, local control. Tumor volume did not reach significance for any of the end points. Lenght of chemotherapy cycles (three or five days) did not reach significance for any of the endpoints. Toxicity was acceptable in both groups. CRT had best outcome in LC: 68% versus 42% in HART; and 25% in CFRT. Five-year OS was much better in CRT than in CFRT: 52% versus 17%. Conclusions: The results of treatment depend on performance status, patients age, tumor mobility and unresectability based on earlier laparotomy. The lack of influence of the tumor volume on all endpoints indicates the need for radical neoadjuvant treatment independently of tumor volume and underlines the key role of a proper surgical treatment. In patients not suitable for CRT, HART is optimal strategy for its better efficacy than CFRT.

Stromal Fibroblasts Counteract the Caveolin-1-Dependent Radiation Response of LNCaP Prostate Carcinoma Cells.

In prostate cancer (PCa), a characteristic stromal–epithelial redistribution of the membrane protein caveolin 1 (CAV1) occurs upon tumor progression, where a gain of CAV1 in the malignant epithelial cells is accompanied by a loss of CAV1 in the tumor stroma, both facts that were correlated with higher Gleason scores, poor prognosis, and pronounced resistance to therapy particularly to radiotherapy (RT). However, it needs to be clarified whether inhibiting the CAV1 gain in the malignant prostate epithelium or limiting the loss of stromal CAV1 would be the better choice for improving PCa therapy, particularly for improving the response to RT; or whether ideally both processes need to be targeted. Concerning the first assumption, we investigated the RT response of LNCaP PCa cells following overexpression of different CAV1 mutants. While CAV1 overexpression generally caused an increased epithelial-to-mesenchymal phenotype in respective LNCaP cells, effects that were accompanied by increasing levels of the 5′-AMP-activated protein kinase (AMPK), a master regulator of cellular homeostasis, only wildtype CAV1 was able to increase the three-dimensional growth of LNCaP spheroids, particularly following RT. Both effects could be limited by an additional treatment with the SRC inhibitor dasatinib, finally resulting in radiosensitization. Using co-cultured (CAV1-expressing) fibroblasts as an approximation to the in vivo situation of early PCa it could be revealed that RT itself caused an activated, more tumor-promoting phenotype of stromal fibroblats with an increased an increased metabolic potential, that could not be limited by combined dasatinib treatment. Thus, targeting fibroblasts and/or limiting fibroblast activation, potentially by limiting the loss of stromal CAV1 seems to be absolute for inhibiting the resistance-promoting CAV1-dependent signals of the tumor stroma.

Hypoxia induces radioresistance, epithelial‑mesenchymal transition, cancer stem cell‑like phenotype and changes in genes possessing multiple biological functions in head and neck squamous cell carcinoma.

Hypoxia has been linked with increased resistance to treatment in various solid tumors, including head and neck squamous cell carcinoma (HNSCC). The aim of the present study was to identify genes involved in hypoxia-mediated responses to radiotherapy in HNSCC. A total of three HNSCC cell lines with an epithelial phenotype were selected for this study and cultured under normoxic (21% O2) or hypoxic (1% O2) conditions. The sensitivity of the HNSCC cells to radiotherapy was assessed by a crystal violet assay. Western blotting (for protein expression), cDNA microarrays and reverse transcription-quantitative PCR (for gene expression) were also applied. Small interfering RNA silencing was used to knock down target genes. The results revealed that hypoxia negatively affected the response of HNSCC cells to radiotherapy. Of note, increased levels of N-cadherin, vimentin and fibronectin, as well as stem cell-associated transcription factors, were observed under hypoxia. The microarray analysis revealed a number of hypoxia-regulated genes that were involved in multiple biological functions. However, downregulation of hypoxia-regulated genes did not affect sensitivity to radiotherapy of the investigated cell lines. Taken together, the present findings indicated several important pathways and genes that were involved in hypoxia and radiotherapy resistance. It is hypothesized that panels of reported hypoxia-regulated genes may be useful for the prediction of radiotherapy responses in patients with HNSCC.

An 11-Gene Signature Based on Treatment Responsiveness Predicts Radiation Therapy Survival Benefit Among Breast Cancer Patients.

PurposeWe developed a strategy of building prognosis gene signature based on clinical treatment responsiveness to predict radiotherapy survival benefit in breast cancer patients.Methods and MaterialsAnalyzed data came from the public database. PFS was used as an indicator of clinical treatment responsiveness. WGCNA was used to identify the most relevant modules to radiotherapy response. Based on the module genes, Cox regression model was used to build survival prognosis signature to distinguish the benefit group of radiotherapy. An external validation was also performed.ResultsIn the developed dataset, MEbrown module with 534 genes was identified by WGCNA, which was most correlated to the radiotherapy response of patients. A number of 11 hub genes were selected to build the survival prognosis signature. Patients that were divided into radio-sensitivity group and radio-resistant group based on the signature risk score had varied survival benefit. In developed dataset, the 3-, 5-, and 10-year AUC of the signature were 0.814 (CI95%: 0.742–0.905), 0.781 (CI95%: 0.682–0.880), and 0.762 (CI95%: 0.626–0.897), respectively. In validation dataset, the 3- and 5-year AUC of the signature were 0.706 (CI95%: 0.523–0.889) and 0.743 (CI95%: 0.595–0.891). The signature had higher predictive power than clinical factors alone and had more clinical prognosis efficiency. Functional enrichment analysis revealed that the identified genes were mainly enriched in immune-related processes. Further immune estimated analysis showed the difference in distribution of immune micro-environment between radio-sensitivity group and radio-resistant group.ConclusionsThe 11-gene signature may reflect differences in tumor immune micro-environment that underlie the differential response to radiation therapy and could guide clinical-decision making related to radiation in breast cancer patients.

Association Between Histopathological Grade of Sarcoma and Radiotherapeutical Response.

BackgroundSarcomas are rare, aggressive tumors originating from mesenchymal tissue. Radiotherapy is currently accepted as thestandard adjuvant to the treatment of high-grade sarcomas, whereas low-grade sarcomas are controversial, but the response ofradiotherapy to sarcomas is up to 50%. The aim of this study was to determine the association between the histopathologicalgrade of sarcoma and the radiotherapeutical response.MethodsThe research design was a cross-sectional study, with retrospective analysis. The sample consisted of 80 paraffin block tissuesfrom biopsy and surgery specimens of sarcoma from January 2013 to December 2019 at Hasan Sadikin Hospital in Bandung,consisting of 45 radiosensitive samples and 35 radioresistant samples. All samples were assessed for histopathological gradeaccording to the FNCLCC. Statistical analysis used the Chi-Square test with a significant value of p &lt;0.05. Data were processedusing SPSS version 24.0 for windows.ResultsIn the radiosensitive group, 15 (33.3%) samples were low grade sarcomas and 30 (66.7%) samples were high grade sarcoma.There was no statistically significant association between histopathological grade and radiotherapeutical response in sarcomasp&gt; 0.05 (p = 0.304).ConclusionIn this study, the radiotherapeutical response was not associated to the histopathological grade of sarcoma. This is because ofthe sensitivity of radiotherapy is influenced by other factors including molecular characteristics.

Predictive value of ALDH1 and CD44 positivity for radiotherapy response and prognosis in early-stage glottic laryngeal squamous cell carcinoma.

To evaluate the predictive value of CD44 and aldehyde dehydrogenase 1 (ALDH1) expression for prognosis and radiotherapy (RT) response in patients with early-stage laryngeal cancer receiving RT. Forty-four patients with early-stage laryngeal cancer diagnosed between 2002 and 2016 were included in the study. The correlation between RT response and pre-treatment immunohistochemical ALDH1 and CD44 staining was evaluated. In addition, survival times were compared between groups. The mean age of the 44 patients was 59.8 ±9.0 (43-81) years and 41 were male. There were 20 patients in the non-recurrent group (all men) and 24 patients in the recurrent group (21 men). Immunohistochemical positivity for ALDH1 was found to be a significant risk factor for RT failure (p = 0.0001), whereas CD44 positivity (p = 0.114) and age group (p = 0.287) were not significant. ALDH1 positivity was identified as a significant predictor of DFS and RT sensitivity, while CD44 positivity did not differ according to RT response.

GSTP1 Ile105Val and GPX1 Pro198Leu Polymorphisms and Their Association with Response to Radiotherapy in Nasopharyngeal Carcinoma Patients

Objectives: Radio-resistance poses a major challenge in nasopharyngeal carcinoma (NPC) treatment. Due to individual variations in radio-sensitivity, biomarkers are needed to tailor radiation treatment. Within this frame, the identification of series of genetic signatures mainly SNPs for NPC patients treated with radiotherapy may help to predict treatment outcome and deliver personalized therapy. The aim of this study was to evaluate the possible association between the GSTP1 Ile105Val and GPX1 Pro198Leu polymorphisms and response to radiotherapy in NPC patients. Methods: From September 2016 to October 2018, a total of 101 patients with confirmed NPC, recruited at Mohammed IV Center for Treatment of Cancer of Casablanca, underwent radiotherapy. DNA was extracted from peripheral blood. Genotyping of the GPX1 Pro198Leu and GPX1 Val105Leu polymorphisms was carried out by PCR amplification and DNA sequencing. SPSS was used to analyse the association of GSTP1 and GPX1 genotypes with clinico-pathological features and response to radiotherapy. Results: The genotyping data revealed the presence of only two genotypes namely Pro/Pro (57.4%) and Pro/Leu (40.6%) for GPX1 gene. The allelic frequencies of C and T alleles were 78.7% and 21.3% respectively. For GSTP gene, the homozygous genotypes Val/Val and Leu/Leu were detected in 35.6% and 12.9% of patients respectively. The heterozygous genotype Val/Leu prevailed (51.5%). Allelic frequencies showed the presence of the two alleles A and G in 57.1% and 42.9% patients respectively. Statistical analysis failed to find any significant association between GSTP Val105Ile and GPX1 Pro198Leu genetic polymorphisms and socio-demographic and clinico-pathological features as well as response to radiotherapy (p>0.05). Conclusion: Further research is warranted on the potential role of SNPs within antioxidant defines genes in radiotherapy response and to identify reliable predictive and non-invasive biomarkers for radio-resistance among NPC patients for personalised therapies. Keywords: Nasopharygeal carcinoma, genetic polymorphisms, GSTP1, GPX1, radio-resistance, prognosis

Magnetic Resonance Imaging in the Contemporary Management of Medulloblastoma: Current and Emerging Applications.

Medulloblastoma, the most common malignant primary brain tumor in children, is now considered to comprise of four distinct molecular subgroups-wingless (WNT), sonic hedgehog (SHH), Group 3, and Group 4 medulloblastoma, each associated with distinct developmental origins, unique transcriptional profiles, diverse phenotypes, and variable clinical behavior. Due to its exquisite anatomic resolution, multiparametric nature, and ability to image the entire craniospinal axis, magnetic resonance imaging (MRI) is the preferred and recommended first-line imaging modality for suspected brain tumors including medulloblastoma. Preoperative MRI can reliably differentiate medulloblastoma from other common childhood posterior fossa masses such as ependymoma, pilocytic astrocytoma, and brainstem glioma. On T1-weighted images, medulloblastoma is generally iso- to hypointense, while on T2-weighted images, the densely packed cellular component of the tumor is significantly hypointense and displays restricted diffusion on diffusion-weighted imaging. Following intravenous gadolinium, medulloblastoma shows significant but variable and heterogeneous contrast enhancement. Given the propensity of neuraxial spread in medulloblastoma, sagittal fat-suppressed T1-postcontrast spinal MRI is recommended to rule out leptomeningeal metastases for accurate staging. Following neurosurgical excision, postoperative MRI done within 24-48h confirms the extent of resection, accurately quantifying residual tumor burden imperative for risk assignment. Post-treatment MRI is needed to assess response and effectiveness of adjuvant radiotherapy and systemic chemotherapy. After completion of planned therapy, surveillance MRI is recommended periodically on follow-up for early detection of recurrence for timely institution of salvage therapy, as well as for monitoring treatment-related late complications. Recent studies suggest that preoperative MRI can reliably identify SHH and Group 4 medulloblastoma but has suboptimal predictive accuracy for WNT and Group 3 tumors. In this review, we focus on the role of MRI in the diagnosis, staging, and quantifying residual disease; post-treatment response assessment; and periodic surveillance, and provide a brief summary on radiogenomics in the contemporary management of medulloblastoma.

Robust extraction of biological information from diffusion-weighted magnetic resonance imaging during radiotherapy using semi-automatic delineation.

Diffusion-Weighted Magnetic Resonance imaging (DWI) quantifies water mobility through the Apparent Diffusion Coefficient (ADC), a promising radiotherapy response biomarker. ADC measurements depend on manual delineation of a region of interest, a time-consuming and observer-dependent process. Here, the aim was to introduce and test the performance of a new, semi-automatic delineation tool (SADT) for ADC calculation within the viable region of the tumour. Thirty patients with rectal cancer were scanned with DWI before radiotherapy (RT) (baseline) and two weeks into RT (week 2). The SADT was based on intensities in b=1100smm-2 DWI and derived ADC maps. ADC values measured using the SADT and manual delineations were compared using Bland-Altman- and correlation analyses. Delineations were repeated to assess intra-observer variation, and repeatability was estimated using repeated DWI scans. ADC measured using the SADT and manual delineation showed strong and moderate correlation at baseline and week 2, respectively, with the SADT measuring systematically smaller values. Intra-observer ADC variation was slightly smaller for the SADT compared to manual delineation both at baseline, [-0.00; 0.03] vs. [-0.02; 0.04] 10-3mm2s-1, and week 2, [-0.01; 0.00] vs. [-0.04; 0.07] 10-3mm2s-1 (68.3% limits of agreement). The ADC change between baseline and week 2 was larger than the ADC uncertainty ( 0.04·10-3mm2s-1) in all cases except one. The presented SADT showed performance comparable to manual expert delineation, and with sufficient consistency to allow extraction of potential biological information from the viable tumour.

Predictor Value of PD-L1 for Radiotherapy Response in Locally Advanced Non-Small Cell Lung Cancer

Predictor Value of PD-L1 for Radiotherapy Response in Locally Advanced Non-Small Cell Lung Cancer

Combined Radiomics-Clinical Model to Predict Radiotherapy Response in Inoperable Stage III and IV Non-Small-Cell Lung Cancer.

Purpose: Radiotherapy is a promising treatment option for lung cancer, but patients' responses vary. The purpose of the study was to investigate the potential of radiomics and clinical signature for predicting the radiotherapy sensitivity and overall survival of inoperable stage III and IV non-small-cell lung cancer (NSCLC) patients. Materials: This retrospective study collected 104 inoperable stage III and IV NSCLC patients at the Yunnan Cancer Hospital from October 2016 to September 2020. They were divided into radiation-sensitive and non-sensitive groups. We used analysis of variance (ANOVA) to select features and support vector machine (SVM) to build the radiomic model. Furthermore, the logistic regression method was used to screen out clinically relevant predictive factors and construct the combined model of radiomics-clinical features. Finally, survival was estimated using the Kaplan-Meier method. Results: There were 40 patients in the radiation-sensitive group and 64 in the non-sensitive group. These patients were divided into training set (73 cases) and testing set (31 cases) according to the ratio of 7:3. Nine radiomics features and one clinical feature were significantly associated with radiotherapy sensitivity. Both the radiomics model and combined model have good predictive performance (the areas under the curve (AUC) values of the testing set were 0.864 (95% confidence interval [CI]: 0.683-0.996) and 0.868 (95% CI: 0.689-1.000), respectively). Only platelet level status was associated with overall survival. Conclusion: The combined model constructed based on radiomics and clinical features can effectively identify the radiation-sensitive population and provide valuable clinical information. Patients with higher platelet levels may have a poor prognosis.

An Activatable Hybrid Organic-Inorganic Nanocomposite as Early Evaluation System of Therapy Effect.

Delays in evaluating cancer response to radiotherapy (RT) usually reduce therapy effect or miss the right time for treatment optimization. Hence, exploring timely and accurate methods enabling one to gain insights of RT response are highly desirable. In this study, we have developed an apoptosis enzyme (caspase-3) activated nanoprobe for early evaluation of RT efficacy. The nanoprobe bridged the nanogapped gold nanoparticles (AuNNPs) and the second near-infrared window (NIR-II) fluorescent (FL) molecules (IR-1048) through a caspase-3 specific peptide sequence (DEVD) (AuNNP@DEVD-IR1048). After X-ray irradiation, caspase-3 was activated to cut DEVD, turning on both NIR-II FL and PA imaging signals. The increased NIR-II FL/PA signals exhibited a positive correlation with the content of caspase-3. Moreover, the amount of the activated caspase-3 was negatively correlated with the tumor size. The results underscore the role of the caspase-3 activated by X-ray irradiation in bridging the imaging signals variation and tumor inhibition rate. Overall, activatable NIR-II FL/PA imaging was successfully used to timely predict and evaluate the RT efficacy. The evaluation system based on biomarker-triggered living imaging has the capacity to guide treatment decisions for numerous cancer types.

An Activatable Hybrid Organic–Inorganic Nanocomposite as Early Evaluation System of Therapy Effect

AbstractDelays in evaluating cancer response to radiotherapy (RT) usually reduce therapy effect or miss the right time for treatment optimization. Hence, exploring timely and accurate methods enabling one to gain insights of RT response are highly desirable. In this study, we have developed an apoptosis enzyme (caspase‐3) activated nanoprobe for early evaluation of RT efficacy. The nanoprobe bridged the nanogapped gold nanoparticles (AuNNPs) and the second near‐infrared window (NIR‐II) fluorescent (FL) molecules (IR‐1048) through a caspase‐3 specific peptide sequence (DEVD) (AuNNP@DEVD‐IR1048). After X‐ray irradiation, caspase‐3 was activated to cut DEVD, turning on both NIR‐II FL and PA imaging signals. The increased NIR‐II FL/PA signals exhibited a positive correlation with the content of caspase‐3. Moreover, the amount of the activated caspase‐3 was negatively correlated with the tumor size. The results underscore the role of the caspase‐3 activated by X‐ray irradiation in bridging the imaging signals variation and tumor inhibition rate. Overall, activatable NIR‐II FL/PA imaging was successfully used to timely predict and evaluate the RT efficacy. The evaluation system based on biomarker‐triggered living imaging has the capacity to guide treatment decisions for numerous cancer types.

Analysis of PET parameters predicting response to radiotherapy for myeloid sarcoma.

PurposePositron-emission tomography (PET)-CT has recently been used for diagnostic imaging and radiotherapy for myeloid sarcoma, but there is little research on predicting the response of radiotherapy. The aim of this study was to analyze the association between PET-CT variables and the response to radiotherapy in patients with myeloid sarcoma.Materials and methodsThis study was conducted in myeloid sarcoma patients who received radiotherapy and PET-CT before and after radiotherapy. The response to radiotherapy was evaluated based on the European Organization for Research and Treatment of Cancer PET response criteria, and binary regression analysis was performed to assess the factors predicting reductions in the maximum standardized uptake value (SUVmax).ResultsTwenty-seven sites in 12 patients were included in the study. Complete metabolic responses were seen in 24 patients after radiotherapy, a partial metabolic response in one, and progressive metabolic disease in two patients. The prescribed dose of more than 3000 cGy10 was significantly greater in the treatment control group (P = 0.024). In binary logistic regression analysis predicting reductions in the SUVmax of more than 70% after radiotherapy, the pretreatment SUVmax (≥ 7.5) and further chemotherapy after radiotherapy showed significant differences in univariate and multivariate analyses.ConclusionGood metabolic responses (complete or partial) to radiotherapy were achieved in 92.6% of the myeloid sarcoma patients. Radiation doses < 3000 cGy10 and increased SUVmax were related to treatment failure and high SUVmax before radiotherapy was a factor influencing SUVmax reduction. Further large-scale studies are needed.

Preliminary exploration of response the course of radiotherapy for stage III non-small cell lung cancer based on longitudinal CT radiomics features

PurposeExplore the longitudinal CT-based radiomics to demonstrate the changing trend of radiotherapy response and to determine at which point after the onset of treatment radiomics exhibit the greatest change for stage III NSCLC patients. Methods and materialsTen stage III NSCLC patients in line with inclusion criteria were enrolled retrospectively, each of whom received radiotherapy or concurrent chemo-radiotherapy and performed eight series of follow-up CT imaging. Longitudinal radiomics were extracted on region of interest from the eight registered images, then two steps were conducted to select significant features as indicators of tumor change: 1) stable features were selected by Kendall rank correlation; 2) texture feature types with a steadily changing trend were retained and intensity features with stable change trends were selected to represent the large number of them. Next, the trend and rate of tumor change were analyzed using the Delta method and Curve-fitting method. Finally, the statistics in the distribution of stable features in patients were calculated. Results675 stable features were selected from a total number of 1371 radiomics features, then 12 texture features types were retained and three intensity features were chosen to represent their own category. Among the final selected feature types, it was found that the two time points were weeks 1 and 3 with the higher rate of change. One patient had very few stable tumor features out of a total of 101 features, and the rate of change of features of another patient was conspicuously higher than the average level with number of 301 features. ConclusionThe longitudinal CT radiomics could demonstrate the change trend of tumor and at which point exhibit the greatest change during radiotherapy, and potentially be used for treatment decisions concerning adaptive radiotherapy.